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pupillary constriction on the affected side.  Pericardial or pleural effusions, and bronchial obstruction leading to atelectasis, 
pneumonia, and lung abscess  
 
Paraneoplastic syndromes: 
• Occur in 10 – 15% of bronchogenic carcinoma and the manifestations are related to 
ectopic hormone secretions by tumor cells . The manifestations could be systemic, or 
related to different systems.  
• Systemic symptoms such as anorexia, cachexia, weight loss and fever may occur in 
30% of cases.  
• Another third of patients with bronchogenic carcinoma may present with endocrine 
manifestations like hypercalcemia or hy pocalcaemia (from ectopic secretion of 
parathormone or calcitonin), Cushing’s syndr ome (from ectopic secretion of ACTH),


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Internal Medicine 
 
 201gyneacomastia (from ectopic secretion gonadotrophins)  and inappropriate release of 
ADH causing Na+ & water retention.  
• Additionally patients may present with clubbing, migratory thrombophlebitis, cerebellar 
degeneration, neuropathies and myopathies such as Eaton-Lambert syndrome or 
myasthenia gravis, anemia, and thrombocytopenic purpura.  
 
Diagnosis 
Screening  
• Is mandatory for men over 45 years, and those smoking more than 40 cigarettes/day 
• Screened tumors were resectable in 62% of cases, and nonscreened tumors were 
resectable only in 20%.  
• Can be done by sputum cytology (to detect malignant cells), and CXR. CXR usually 
demonstrates solitary pulmonary nodule and about 35% of such cases are due to 
bronchogenic carcinoma.  
Other investigations commonly used to make the diagnosis and staging of lung tumors, most of which are available in specialized hospitals  
• Lymph node biopsy from enlarged scalene or supraclavicular LN to detect 
metastasis 
• Mediastinoscopy  
• Bronchoscopy 
• Thoracenthesis to collect fluid for cytology 
• Pleural biopsy  
Management 
1.  Non-small cell carcinoma  
• Surgical excision is curative for patient with ipsilateral lymph node involvement but 
without local/distant spread or contralateral lymph node involvement. 
 Intrathoracic disease - radiotherapy is palliative  
 Pancoast  syndrome – radiotherapy/chemotherapy


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without local/distant spread or contralateral lymph node involvement. 
 Intrathoracic disease - radiotherapy is palliative  
 Pancoast  syndrome – radiotherapy/chemotherapy 
 Extrathoracic disease – analgesics, radiot herapy, dexamethasone, obliteration of the 
pleural cavity 
2. Small cell carcinoma  
 By the time of diagnosis 95% of these tumors have metastasized  
 Responsive for chemotherapy +/- radiotherapy


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Internal Medicine 
 
 2023. Bronchial adenomas, carcinoids need surgical resection 
 Prevention – Cessation of  smoking 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Neoplasms of the lung, pages 506-515. 
2)  Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Carcinoma of the lung, 169-172.


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Internal Medicine 
 
 203CHAPTER THREE 
DISEASES OF THE CA RDIOVASCULAR SYSTEM 
 
Introduction  
The epidemic of cardiovascular diseases (CVDs) is accelerating globally over all regions and 
social classes. This is reflected in the high burden as well as the estimated escalation of those 
burdens over the next two decades. Most current global burden of CVD as well as all of the expected future augmentation of this burden is attributable to the change in the life style of 
people. Even in the setting of a 'double burden' of disease which is experienced by the 
developing countries, CVD contributes to a large proportion of morbidity and mortality. 
  
 A major study by WHO and Harvard School of Public Health published in 1996, predicted 
massive rise of non-communicable diseases (NCDs ), most of this rise taking place in the 
developing world. Already, according to the author of this report, adults under the age of 70 in Africa face a higher probability of death from NCD than their counterparts in the West. The number of people living with a disability is also set to increase.  
 A number of reasons underlie the expected rise in CVD in the developing world:  
1. An overall increase in the population.  
2. Improved life expectancy is leading to more person living to the middle age and beyond , 
which increase the risk of CVD 
3. Lifestyle transition:-increase urbanization, industrialization, globalization and change in 
nutritional habit.


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2. Improved life expectancy is leading to more person living to the middle age and beyond , 
which increase the risk of CVD 
3. Lifestyle transition:-increase urbanization, industrialization, globalization and change in 
nutritional habit. 
4. Past or current nutrition deprivation in utero and early childhood may affect 
cardiovascular health trend. Lack of weight gain in the first year of life and low birth weight in spite of maternal weight gain have been linked to coronary disease in adult life.  
The causes of cardiovascular diseases in developing countries include:- 
• Chronic rheumatic heart disease 
• Hypertensive heart disease 
• Cardiomyopathies 
• Congenital heart disease.  
• Ischemic heart disease:


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Internal Medicine 
 
 204There are indicators of increasing prevalence of ischemic heart diseases due to the existence of 
risk factors in some segment of the population: hypertension, smoking, diabetes, hypercholesterolemia, and obesity.  
There are very few studies about CVD in Ethiopia.  The prevalence of rheumatic heart disease 
is 6/1000 in school children. Analysis of admi tted cases, to medical ICU of Tikur Anbessa 
Hospital from 1988 to 1997 (in Addis Ababa, Ethiopia) has showed that acute myocardial infraction (AMI) was the third cause of ICU admission, and AMI annual admission increased 
consistently. Moreover, from one year (1998 - 1999) autopsy study done in Minilik II Hospital to 
investigate the cause of sudden death in Addis Ababa, 70% (44/63) deaths were found to be due to coronary artery disease.   The implication of a CVD epidemic is devastating to developing countries in general and to 
Ethiopia in particular, as there are few community-based programs and government policies to 
limit the spread of deleterious health behaviors.  Therefore, there is a need to carry out appropriate preventive strategies to tackle the problem.


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Internal Medicine 
 
 2051.  Rheumatic Fever  
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define rheumatic fever 
2. Understand the etiologic agents of rheumatic fever  3. Understand  the Epidemiology of rheumatic fever  
4. Describe the pathogenesis of rheumatic fever   
5. Identify the clinical manifestation of rheumatic fever  6. Understand the diagnostic approach of rheumatic fever 7. Manage patients having  rheumatic fever  8. Design strategies for prevention of rheumatic fever  
 Background: Rheumatic fever causes chronic progressive damage to the heart and its valves 
.The association between sore throat and rheumatic fever was not made until 1880. The dramatic decline in the incidence of rheumatic fever in the developed world is thought to be 
largely owing to antibiotic treatment of streptococcal infection, though it stated to decline before 
the era of antibiotic, probably due improvement of socioeconomic status.  
 
Epidemiology  
• Even though the overall incidence of RF and  RHD in developed countries has sharply 
declined, rheumatic fever is the commonest cause of heart disease in the developing countries. In those countries, more than 50% of heart disease is accounted for rheumatic 
heart disease (RHD). Even in developing countries, the prevalence of RF and RHD varies 
between rural and urban areas. 
• The Prevalence of RF ranges from 3 to 12/1000 population in the developing country with the 
peak age of 5-15 years.


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heart disease (RHD). Even in developing countries, the prevalence of RF and RHD varies 
between rural and urban areas. 
• The Prevalence of RF ranges from 3 to 12/1000 population in the developing country with the 
peak age of 5-15 years.  
• In adult the risk developing of RF is about 3% following group A Streptococcal (GAS) 
Pharyngitis with a recurrence rate of 1/6. 
• The high attack rate of group A Streptococcal pharyngitis in families, institutions and military 
recruits is the result of contact among susceptible persons living closely enough to ensure droplet transmission.  
• Risk factors for RF include low socioeconomic status with associated over crowded living 
condition. However, RF is not associated with streptococcal skin infection (pyoderma).


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Internal Medicine 
 
 206Pathophysiology 
• Acute rheumatic fever is a sequel of a previous group A streptococcal infection, usually 
of the upper respiratory tract. One beta-streptococcal serotype (e.g., M types 3, 5, 18, 
19, 24) is linked directly to acute rheumatic fever. Rheumatogenicity of GAS is important 
factor as not all GAS pharyngitis is associated with development of rheumatic fever. 
• Rheumatic fever follows Lancefield β hemolytic streptococcus pharyngitis within the 
interval of 2-3 weeks.   
The mechanism is elusive, but the followings are proposed ones: 
• Dysfunction of the immune Response   
• Antigenic Mimicry  
o Similarity between the carbohydrate moiety if GAS and glycoprotein of heart 
valve  
o Molecular similarity between some Streptococcal antigens and sarcolema or 
other moiety of human myocardial cells. 
• Several host related factors have been identified to have operated in relation to specific 
genetic function and difference in the immune response of individuals.    
• The disease involves the heart, joints, ce ntral nervous system (CNS), skin, and 
subcutaneous tissues. It is characterized by  an exudative and proliferative inflammatory 
lesion of the connective tissue, especially that of the heart, joints, blood vessels, and subcutaneous tissue. 
Clinical Manifestation 
Acute rheumatic fever is associated with 2 distinct patterns of presentation. 
• The first pattern of presentation is sudden onset. It typically begins as polyarthritis 2-6


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Clinical Manifestation 
Acute rheumatic fever is associated with 2 distinct patterns of presentation. 
• The first pattern of presentation is sudden onset. It typically begins as polyarthritis 2-6 
weeks after streptococcal pharyngitis, and it  is usually characterized by fever and 
toxicity. 
• The second pattern is insidious or subclinical and the initial abnormality is mild carditis. 
• Age at onset influences the order of complications. Younger children tend to develop 
carditis first, while older patients tend to develop arthritis first. 
Diagnosis :  
Diagnosis of acute rheumatic fever requires a high index of suspicion. Jones criteria developed by the American Heart Association is used to make the diagnosis.


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Internal Medicine 
 
 207Table III -1 -1 Jones criteria for the diagnosis of acute rheumatic fever.   
 
Major Criteria   Minor Criteria  
Carditis Migratory ply arthritis  Sydenham’s Chorea Subcutaneous nodules  
Erythema marginatum Clinical  
     Fever      Arthralgia Laboratory   
     Elevated acute phase reactants : ESR, 
CRP       Prolonged PR interval 
Plus 
Supportive evidence of recent Group A streptococcal infection ( e.g. positive throat culture or 
rapid antigen detection test ; and/or elevated or increasing streptococcal antibody test : ASO 
titer , Anti DNAase , Anti NADase etc ) 
JAMA: 268, 2069, 1992. 
 
 In addition to evidence of a previous streptococcal infection, the diagnosis of acute rheumatic 
fever requires 2 major Jones criteria or 1 major plus 2 minor Jones criteria. 
 1) Carditis,  (pancarditis here), occurs in as many as 40- 60% of patients and may manifest as:  
a) New murmur 
b) Cardiomegaly 
c) Congestive heart failure  d) Pericarditis with or without a pericardial rub and resolve without squeal of constriction.   e) Valvular disease: mitral and aortic valves  are commonly affected. Healing of rheumatic 
valvulitis will lead into fibrous thickening and adhesion, resulting in progressive valvular damage. But, about 80% of mild valvulitis wo uld resolve. There is a risk of developing 
endocarditis on a damaged valve.  
2) Migratory polyarthritis  occurs in 75% of cases and involves many joints at a time. The 
larger joints are mainly affected.


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endocarditis on a damaged valve.  
2) Migratory polyarthritis  occurs in 75% of cases and involves many joints at a time. The 
larger joints are mainly affected. 
3) Subcutaneous nodules : occur in 10% of patients and are edematous fragmented collagen 
fibers. They are firm painless nodules on the ext ensor surfaces of wrists, elbows, and knees.


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Internal Medicine 
 
 2084) Erythema marginatum occurs in about 5% of cases. The rash is serpiginous and long 
lasting. 
5) Sydenham’s chorea  (i.e., St Vitus’ dance) is a characteristic movement disorder that 
occurs in 5-10% of cases. Sydenham’s chorea consists of rapid purposeless movements of 
the face and upper extremities. Onset may be delayed for several months to years and may cease when the patient is asleep. 
Laboratory Studies:  
• No specific confirmatory laboratory tests exis t. However, several laboratory findings indicate 
continuing rheumatic inflammation. Some are part of the Jones minor criteria. 
• Supportive evidences                        
o Streptococcal antibody tests disclose preceding streptococcal infection 
 ASO titer: positive in 80% of cases   
 Anti DNAase β & Anti hyaluronidase is positive in 95 % of cases 
o Isolate group A streptococci via throat culture which has 20-40% yield.  
• Laboratory minor criteria  
o Acute phase reactants (e.g. raised ESR and  C-reactive protein [CRP])   
o Leukocytosis may be seen. 
o Anemia usually is caused by suppression of erythropoiesis. 
o ECG: PR interval prolongation is seen in 25% of all cases but is neither specific to nor 
diagnostic. 
Treatment  
Medical therapy involves the following 5 areas:  
1. Treat group A streptococcal infection  regardless of organism detection.  
All patients with acute rheumatic fever should be given appropriate antibiotic.


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diagnostic. 
Treatment  
Medical therapy involves the following 5 areas:  
1. Treat group A streptococcal infection  regardless of organism detection.  
All patients with acute rheumatic fever should be given appropriate antibiotic.  
o Ampicillin 500 mg PO QID or Amoxicillin 500 mg PO TID  for 10 days or 
o Benzathin penicillin 1.2 million IU IM single dose or  
o Erythromycin 500 mg PO QID for 10 days ( for penicillin allergic patient) 
2. Therapy for manifestation of acute rheumatic fever   
Arthritis: 
o ASA is given at dose 2 gm four times per day for 4-6 weeks, no indication for 
steroids.  
Carditis  
Severe Carditis with congestive heart failure should be treated with


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Internal Medicine 
 
 209o Prednisolone 60 to 80 mg /day, to be tapered as patient improves  
o Start ASA during tapering phase to be given for 4-6weeks 
o But both have no influence on the future development of valvular heart disease 
(VHD).   
 
Congestive heart failure: Treats by conventional therapy such as digoxin  and diuretics.    
Sydenham’s chorea : In majority of the cases it is self-limiting. But in symptomatic patients 
benzodiazepines (diazepam) or phenothiazines ( haloperidol) may be helpful in controlling 
symptoms.  
3.  Administer secondary prophylaxis:  is indicated for all patients with rheumatic fever.  
Taking benzathin penicillin is the first choice for better compliance and longer prevention.  
• Benzathin penicillin 1.2 million IU IM every 4 weeks , but if the there is high risk of 
recurrence, it can be given every 3weeks  
Alternative antibiotics  
• Oral penicillin V (250mg twice/day)  
• Oral sulfadiazine (1g/day)  
N.B. In a patient with an established RHD, it is  advisable to get the prophylaxis lifelong.  
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Rheumatic fever , pages 1977-1978


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Internal Medicine 
 
 2102. Congestive Heart Failure  
 
Learning objectives: at the end of this lesson the student will be able to  : 
1. Define congestive heart failure. 2. List the etiologic agents of congestive heart failure.   3. Understand the Epidemiology of congestive heart failure.  
4. Describe the pathophysiology of congestive heart failure.   
5. Identify the clinical manifestation of congestive heart failure. 6. Understand the diagnostic approach of congestive heart failure. 7. Manage patients with congestive heart failure. 
8. Design strategies for prevention of congestive heart failure . 
 
Definition: 
• Heart failure is a clinical syndrome charac terized by inadequate systemic perfusion to meet 
the body's metabolic demands as a result of abnormalities of cardiac structure or function.  
• This may be further subdivided into either systolic or diastolic heart failure.  
o Systolic heart failure: there is reduced cardiac contractility 
o Diastolic heart failure there is impaired cardiac relaxation and abnormal 
ventricular filling.  
• The body, sensing inadequate organ perfusion, activates multiple systemic neurohormonal 
pathways which compensate initially by redistributing blood flow to vital organs but later 
exacerbate the patient's symptoms and lead to clinical deterioration. 
 Etiology:


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pathways which compensate initially by redistributing blood flow to vital organs but later 
exacerbate the patient's symptoms and lead to clinical deterioration. 
 Etiology:  
The most common cause of heart failure is left ventricular systolic dysfunction (about 60% to 70% of patients). The following are some of the underlying causes of heart failure . 
1) Decreased contractile function  
a. Valvular heart disease  
b. Coronary Heart Disease : Myocardial ischemia 
c. Myocardial Disease : C adiomyopathy , Myocarditis  
2) Increased after load   
a. Acute systemic hypertension  
3) Abnormalities in preload


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Internal Medicine 
 
 211a. Excessive preload  
b. Reduced preload  
4) Reduced compliance states: Constrictive pericarditis , Restrictive cardiomyopathy 
Precipitating factors for heart failure:  
• These are relatively acute disturbances t hat place an additional load on a myocardium 
that is chronically and excessively burdened.  
• In compensated state patients are asympt omatic; however as patients have little 
additional reserve, they become symptomatic in the presence of these precipitating factors.  
• Knowing the precipitating factors is important because most of the time they are 
treatable and the cardiac function improves when these precipitating factors are treated 
or avoided. 
The most important precipitating factors may be represented with the mnemonic, HEART 
FAILES    
H- Hypertension (systemic)  
E- Endocarditis (infections)  
A- Anemia R- Rheumatic fever and myocarditis  T- Thyrotoxicosis and pregnancy  
F- Fever (infections)  
A- Arrhythmia  I- infarction (myocardial)  L- Lung   infection  E- Embolism (pulmonary)  
S- Stress (emotional, physical, environment, dietary, fluid excess)  
Pathophysiology  
• In left ventricular systolic dysfunction, regar dless of the etiology, cardiac output is low 
and pulmonary pressures are high, leading to pulmonary congestion. As a result, a series of adaptive mechanisms are activated. Initially, as a direct result of inadequate


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and pulmonary pressures are high, leading to pulmonary congestion. As a result, a series of adaptive mechanisms are activated. Initially, as a direct result of inadequate 
cardiac output and systemic perfusion, the body activates several neurohormonal pathways in order to increase circulating blood volume.  
• With continuous neurohormonal stimulation, the left ventricle undergoes remodeling with 
left ventricular dilatation and hypertrophy, such that stroke volume is increased without


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Internal Medicine 
 
 212an actual increase in ejection fraction. Thi s is achieved by myocyte hypertrophy and 
elongation. However, left ventricular chamber dilatation causes increased wall tension, 
worsens subendocardial myocardial perfusion, and may provoke ischemia in patients 
with coronary atherosclerosis. Furthermore, left ventricular chamber dilatation may 
cause separation of the mitral leaflets and mitral regurgitation with worsening of pulmonary congestion. Enhanced neurohormonal stimulation of the myocardium also causes apoptosis, or programmed cell death, leading to worsening of ventricular 
contractility. 
 
Clinical Manifestations   
• Progressive dyspnea which initially occurs with exertion and later occurs at rest. 
Dyspnea on exertion has been found to be the most sensitive complaint, yet the specificity for dyspnea is less than 60%. 
• Orthopnea and paroxysmal nocturnal dyspnea (PND) are more specific symptoms; 
however, sensitivity for orthopnea and PND is only 20-30%. 
• Cough productive of pink, frothy sputum is highly suggestive of CHF. Wheezing may 
also occur. 
• Peripheral edema and ascites  
• Nonspecific complaints include the following: easy fatigability , light headedness , 
malaise  anxiety abdominal pain , nausea etc 
• Past medical history  may include the following: rheumatic fever , alcohol use, 
hypertension , angina , previous history of  myocardial infarction  and familial history of heart disease 
Physical findings:


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• Past medical history  may include the following: rheumatic fever , alcohol use, 
hypertension , angina , previous history of  myocardial infarction  and familial history of heart disease 
Physical findings:  
• Tachycardia and Tachypnea and signs of respiratory distress including use of accessory 
muscles of respiration 
• Jugular venous distention (JVD) frequently is present and engorged neck veins  
• Pulsus alternans (alternating weak and strong pulse indicative of depressed left ventricle 
[LV] function 
• Wheezing or rales may be heard on lung auscultation and there may be bilateral basal 
dullness. 
• Apical impulse frequently is displaced laterally 
• Cardiac auscultation may reveal aortic or mitral valvular abnormalities, S
3 or S 4.


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Internal Medicine 
 
 213• Skin may be diaphoretic or cold, gray, and cyanotic 
• Lower extremity edema also may be noted, especially in the subacute process. 
 
New York Heart Association Heart Failure Classifi cation scheme is used to assess the severity 
of a patient's functional limitations and correlates fairly well with cardiovascular prognosis.   Table III -2-1: New York Heart Association Heart Failure Symptom Classification System  
 
Grade   Symptoms  
I No symptom limitation with ordinary physical activity  
II Ordinary physical activity somewhat limited by dyspnea (i.e., 
long distance walking, climbing 2 flights of stairs)  
III Exercise limited by dyspnea at mild workloads (i.e., short distance walking, climbing one flight of stairs)  
IV Dyspnea at rest or with very little exertion  
 
Diagnostic    Workup  
• Chest x-ray :  the main findings are cardiomegally, pulmonary edema, and pleural 
effusion. 
• Echocardiography : may help identify valvular abnormalities, ventricular dysfunction, 
cardiac temponade, pericardial constriction, and pulmonary embolus. 
• Electrocardiogram (ECG) : is a nonspecific tool but may be useful in diagnosing 
concomitant cardiac ischemia, prior myocardi al infarction (MI), cardiac dysrhythmias, 
chronic hypertension, and other causes of left ventricular hypertrophy.   
• Other laboratory tests : Hemoglobin, Urinalysis, BUN, Creatinine  
 Management of Heart Failure  
Principles of management


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chronic hypertension, and other causes of left ventricular hypertrophy.   
• Other laboratory tests : Hemoglobin, Urinalysis, BUN, Creatinine  
 Management of Heart Failure  
Principles of management  
1. Identify and treat the precipitating factors 
2. Control the congestive state  
3. Improve myocardial performance


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Internal Medicine 
 
 2144. Prevention of deterioration of myocardial function (slowing  progression of heart 
failure )  
5. Treat the underlying cause  
A. General measures :  
• Dietary sodium restriction  should be implemented in all patients with congestive 
heart failure to < 3 g/d.  
• Activity and life style modification   :  
o Meals should be small in quantity but more frequent. 
o Reduce anxiety and emotional stress 
o Avoid excess physical exertion ( NB exer cise may be advised within the limit of 
the patient’s cardiac function )  
o Weight loss in encouraged in obese patients. 
o Cessation of smoking  
o Avoid other CVD risk factors  
B. Control of the Congestive state  
Diuretics: are useful in relieving congestion and reduce or prevent edema.  
Most patients with heart failure have some degree of symptomatic congestion and 
benefit from diuretic therapy.  
Usually a loop diuretic is required, with the addition of a Thiazide diuretic in patients refractory to the loop diuretic alone.  1. Furosomide :   Initial dose 20-40 mg PO 1-2 X daily or 20 mg IV 
Maximum dose 400 mg PO/day or 80 mg IV /day 
2. Hydrochlorothiazide :  Initial dose 25 mg PO/day 
Maximum dose 100 mg PO/day  
• N.B . Loop and thiazide diuretics are useful for symptomatic relief; however they 
have not been shown to improve survival. 
• Side effects : Azotemia, hypokalemia, me tabolic alkalosis and elevation of


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Maximum dose 100 mg PO/day  
• N.B . Loop and thiazide diuretics are useful for symptomatic relief; however they 
have not been shown to improve survival. 
• Side effects : Azotemia, hypokalemia, me tabolic alkalosis and elevation of 
neurohormones   3. Spirinolactone : is an aldosterone inhibitor, reduces mortality in patients with 
advanced heart failure. This drug should be reserved for patients with moderately 
severe or severe heart failure  ( class IV symptoms ) 
Initial dose: 25 mg PO/day or every other day  
Maximum dose: 50 mg PO BID or higher


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Internal Medicine 
 
 215Side effects :  
• Hyperkalemia  is common so monitoring K+ the serum potassium level is 
essential. As a result, this drug should not be used in patients with a 
creatinine above 2.5 mg/dl.  
• Gynecomastia  in men is the other side effect of this drug.  
 
C. Enhancement of Myocardial contractility : 
1) Digoxin:  is a drug which has :  
• Inotropic effect  and acts by inhibiting the Na+-K+ ATPase and increase 
intracellular calcium. This increases myocardial contractility. 
• Neurohormonal modulation  of centrally mediated parasympathomimetic and 
sympatholytic activity.  By doing so it blocks the AV node and delays AV 
conduction. 
o Initial dose : 0.125 mg PO/day    
o Maximum dose : 0.25 mg PO/day  
♦ The use of digoxin can improve symptoms, reduce the duration  and the need for 
hospitalization in patients with  heart failure,, but has no effect on long term survival. 
♦ Digoxin is renally excreted and so dose adjustment is necessary in renal failure.  
♦ A low dose of the drug (0.125 mg daily) should be prescribed, especially in women.  
♦ Digoxin use is recommended for patients with left ventricular systolic dysfunction, 
particularly if they have atrial fibrillation.  
♦ It is relatively contraindicated in some cardiac disease  
o Cardiac outflow obstruction in  MS (in the absence of atrial fibrillation  ) 
o Corpulmonale  
♦ Because of it narrow window of safety, digoxin is associated with different Side 
effects including:


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o Cardiac outflow obstruction in  MS (in the absence of atrial fibrillation  ) 
o Corpulmonale  
♦ Because of it narrow window of safety, digoxin is associated with different Side 
effects including: 
o GI : anorexia , nausea, vomiting , weight loss 
o Neuralgia, delirium 
o Yellow vision  
o Gynecomastia 
o Arrhythmias of different types


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Internal Medicine 
 
 216o Electrolyte on toxicity is suspected, digoxin should be withheld, and has 
observe for some days before reinitiate with a lower dose. One should also 
give KCl, as hypokalemia is increase digoxin toxicity.  
2) Vasodilators:  may be useful in patients with severe acute heart failure who demonstrate 
systemic vasoconstriction despite ACE inhibitor therapy. Through vasodilatation they reduce the peripheral resistance and after load and improve cardiac performance. Hydralazine:  Initial dose:   25 mg PO TID 
              Maximum dose: 150 mg PO QID. 
Isosorbide dinitrate : Initial dose 10 mg PO TID 
               Maximum dose: 80 mg PO TID 
♦ Hydralazine and nitrates in combination are effective afterload reducing agents 
used in ACE-intolerant patients.  
D. Prevention of deterioration of Myocardial function :  
• The following drugs prevent deterioration in myocardial function by inhibiting the 
neurohumeral mechanism which causes cardiac remodelling and progression of heart failure. 
1) Angiotensin Converting Enzyme (ACE) Inhibitors 
Afterload reduction and neurohormonal modulation with ACE inhibitors ( e.g. Captopril, Enalapril, etc)    have been shown to improve mortality, symptoms, and hospitalizations.  
The dose of ACE inhibitors should be titrated to the maximum that can be tolerated symptomatically or the target dose. . 
Initial dose: Captopril 6.25 mg PO/day or every other day  
          Enalapril 2.5 mg PO BID


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The dose of ACE inhibitors should be titrated to the maximum that can be tolerated symptomatically or the target dose. . 
Initial dose: Captopril 6.25 mg PO/day or every other day  
          Enalapril 2.5 mg PO BID   
Maximum dose: Captopril 50-100 mg PO QID         Enalapril 10- 20 mg PO BID 
Side effects of ACE inhibitors 
o Angioedema  
o Acute renal failure I patients with bilateral renal artery stenosis. It is 
contraindicated in a patient with creatinine >3mg/dl 
o Cough  
Contraindications: 
o Angioedema or anuric renal failure  
o Pregnancy  
o Hypotension


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Internal Medicine 
 
 217o Creatinine > 265 mol/L (3mg/dl)  
N.B The first two side effects are serious and necessitate immediate cessation of the 
drug.  
 
2) Angiotensin-II Receptor blocker  
These drugs are useful in patients who cannot tolerate ACE inhibitors due to different 
side effects like cough angioedema and lukopenia. 
Lasortan:  Dose : - 25-50 mg once 0r twice daily 
3) Beta Adrenorecepter  blockers  
Administration of these drugs with gradually increasing dose has been reported to 
improve symptoms of heart failure, the need fo r hospitalization  and reduce mortality. 
They are indicated to moderately severe heart failure.  
They are not indicated in unstable heart failure , hopotensive states , severe fluid 
overload , sinus bradycardia , AV block and asthma. 
Metoprololol:  Initial dose 6.25 mg PO BID 
     Maximum dose: 75 mg PO BID 
   
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Heart 
failure, pages 1367-1377. 
2. Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition Medicine, 
Congestive Heart failure,1-6.


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Internal Medicine 
 
 2183. Valvular Heart Diseases (VHD)   
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define valvular heart diseases. 
2. List the etiologies of valvular heart diseases.  3. Understand the Epidemiology of valvular heart diseases.  
4. Describe the pathogenesis of valvular heart diseases.  
5. Identify the clinical manifestation of different valvular heart diseases.  6. Understand the diagnostic approach of valvular heart diseases. 7. Understand the management of patients having valvular heart diseases.   
Introduction  
• Valvular heart disease from chronic rheumatic fever is still the commonest cardiac 
disease in the developing world, occurring at the younger age. 
• It causes significant morbidity and mortality due to lack of appropriate preventive and 
therapeutic intervention.  
• It accounts for 42 % of cardiac patients attending hospitals in Ethiopia.  
• Generally, patients with stenotic valvular lesions can be monitored clinically until 
symptoms appear. In contrast, patients with regurgitate valvular lesions require careful echocardiographic monitoring for left ventricular function and may require surgery even if no symptoms are present. 
• Aside from antibiotic prophylaxis, very little medical therapy is available for patients with


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• Aside from antibiotic prophylaxis, very little medical therapy is available for patients with 
valvular heart disease; surgery is the treatment for most symptomatic lesions or for lesions causing left ventricular dysfunction even in the absence of symptoms. However surgical management is unavailable for most patients who are suffering from valvular 
heart diseases in Ethiopia.   
 
Aortic Stenosis (AS) 
Aortic stenosis could be caused by 
• Rheumatic carditis 
• Congenital stenosis of aortic valve or 
• Senile/calcific aortic stenosis which is id iopathic results in calcification and degeneration 
of the aortic leaflets.


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Internal Medicine 
 
 219• Persons born with a bicuspid aortic valve are predisposed to develop aortic stenosis. 
 
Clinical features   
 Initially there is an extended latent period duri ng which the patient is asymptomatic. This is 
followed by the classic symptoms of AS: 
• Angina 
• Exertional syncope and  
• Dyspnea 
 Physical Examination  
• The most common physical sign of aortic stenosis is a systolic ejection murmur at left at 
the 2
nd intercostals space that radiates to the neck. In mild aortic stenosis, the murmur 
peaks early in systole, but as the severity  of stenosis increases, the murmur peaks 
progressively later in systole and may become softer as cardiac output decreases 
• As the stenosis worsens, the aortic component of the second heart sound may become 
diminished.  
• The timing and amplitude of the carotid pulse correlate with the severity of aortic 
stenosis. Later in the disease, the carotid upstrokes become diminished and delayed 
(parvus et tardus)  
 Echocardiography  
• Echocardiography with Doppler provides an accurate assessment of aortic valve area 
and transvalvular gradient and also can be used to estimate left ventricular hypertrophy and ejection fraction. 
 
Chest X-ray : may demonstrate valve calcification.  
Management  
Medical Therapy : 
• Is not effective and treatments with digitalis or cautiously administered diuretics may only 
reduce symptoms.  
• Patients with severe aortic stenosis should limit vigorous physical activity.


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Management  
Medical Therapy : 
• Is not effective and treatments with digitalis or cautiously administered diuretics may only 
reduce symptoms.  
• Patients with severe aortic stenosis should limit vigorous physical activity.  
• Patients with aortic stenosis are at moderate risk for development of endocarditis and 
should receive endocarditis prophylaxis before selected procedures.


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Internal Medicine 
 
 220Surgical Therapy   
• Aortic valve replacement is the only effectiv e treatment that will relieve this mechanical 
obstruction.  
Prognosis:  
• The survival of patients with aortic stenosis is  nearly normal until the onset of symptoms, 
when survival rates decrease sharply.  
• Although the rate of progression of aortic stenosis is variable and difficult to predict 
approximately 75 percent of patients with aor tic stenosis will be dead three years after 
the onset of symptoms if the aortic valve is not replaced.  
 
Aortic Regurgitation (AR)  
Aortic regurgitation results from disease affecting the aortic root or aortic leaflets, preventing 
their normal closure.  
Common causes of aortic regurgitation include: 
• Endocarditis 
• Rheumatic fever 
• Collagen vascular diseases 
• Aortic dissection   
• Syphilis 
• Bicuspid aortic valves are also prone to regurgitation. 
♦ In chronic aortic regurgitation, the stroke volume  is increased, which in turn causes systolic 
hypertension, high pulse pressure and increased afterload. The afterload in aortic 
regurgitation may be as high as that occurring in aortic stenosis.  
♦ Patients may be asymptomatic until severe left ventricular dysfunction has developed. The 
initial signs of aortic regurgitation are subtle and may include decreased functional capacity or fatigue. As the disease progresses, the typical presentation is that of left-sided heart failure: orthopnea, dyspnea and fatigue.


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initial signs of aortic regurgitation are subtle and may include decreased functional capacity or fatigue. As the disease progresses, the typical presentation is that of left-sided heart failure: orthopnea, dyspnea and fatigue.  
♦ Systolic dysfunction is initially reversible, with full recovery of left ventricular size and function 
after aortic valve replacement. Over time, how ever, progressive chamber enlargement with 
decreased contractility make recovery of le ft ventricular function and improved survival 
impossible, even with surgery.


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Internal Medicine 
 
 221Physical Examination :  
• A diastolic blowing murmur heard along the left sternal border is characteristic of aortic 
regurgitation. A diastolic rumble may also be heard over the apex.  
• The peripheral signs of hyperdynamic circulation indicate severe disease. Some of these 
include: 
o Wide pulse pressure  
o Collapsing pulse ( water hammer pulse )   
o Quincke's pulse (alternating blanching and erythema of the nailbed with gentle 
pressure applied)   
o De musset's sign (head bobbing) 
o Pistol shot over the femoral artery  
Echocardiography  
• Echocardiography with Doppler ultrasonography provides information about aortic valve 
morphology and aortic root size, and a semiquantitative estimate of the severity of aortic 
regurgitation .It provides valuable information about left ventricular size and function. 
 
Management   
Medical Treatment   
• Diuretics  
• Digoxine: may be indicated in patients with severe regurgitation and dilated left ventricle 
without frank LV failure. 
• Salt restriction  
• Vasodilators: afterload reduction with vasodilators has been shown to improve left 
ventricular performance and reduce aortic regurgitation. ACE inhibitors are the preferred 
vasodilators. Therapy with long acting nifedipine in particular has been shown to delay 
the need for surgery by two to three years. 
• Endocarditis prophylaxis is essential for all patients with AR as their infection tolerance is 
poor.


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vasodilators. Therapy with long acting nifedipine in particular has been shown to delay 
the need for surgery by two to three years. 
• Endocarditis prophylaxis is essential for all patients with AR as their infection tolerance is 
poor. 
 
Surgical management : aortic valve replacement is the definitive treatment for patients with AR. 
There are two important points to consider in deciding the timing of surgery. 
1. Patients with chronic AR usually don’t become symptomatic until after the development 
of myocardial dysfunction


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Internal Medicine 
 
 2222. When delayed too long, surgical treatment often does not restore normal LV function. 
• There for appropriate timing is necessary for surgical intervention.  
Aortic regurgitation should be corrected if the symptoms are more than mild. Compelling 
evidence supports surgical correction before the onset of permanent left ventricular damage, even in asymptomatic patients.
 
 
Mitral Stenosis (MS)  
• Mitral stenosis is sequelae of rheumatic heart disease primarily affecting women.  
• Mitral stenosis has a progressive, lifelong course that is slow and stable in the early 
years, with rapid acceleration later in life.  
• It is very common in the developing countri es manifesting below the age of 20 whereas 
there is generally a latent period of 20 to 40 years between the occurrence of rheumatic 
fever and of mitral stenosis in developed countries.  
• Elevated left atrial pressure eventually causes pulmonary vasoconstriction, pulmonary 
hypertension and compromise of right ventricular function.  
• Many patients remain asymptomatic until atrial fibrillation develops or until pregnancy 
occurs, when there is increased demand on the heart.  
• Symptoms are generally those of left-sided heart failure: dyspnea on exertion, orthopnea 
and paroxysmal nocturnal dyspnea. Patients may also present with hemoptysis, signs of 
right-sided heart failure, and embolic phenomena like stroke.  
Physical Examination


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and paroxysmal nocturnal dyspnea. Patients may also present with hemoptysis, signs of 
right-sided heart failure, and embolic phenomena like stroke.  
Physical Examination  
• An apical rumbling, mid-diastolic murmur is characteristic and will immediately follow an 
opening snap, if present. The rumble is loudest in early diastole but, in patients with mild mitral stenosis or mitral stenosis with low cardiac output, the murmur may be difficult to 
hear. It can be accentuated by placing the patient in the left lateral decubitus position 
and using the bell of the stethoscope. Brief exercise (such as walking in the hallway) may also accentuate the murmur.  
• A loud first heart (S1) sound is common.  
• A right ventricular lift, elevated neck veins, ascites and edema are later signs of right 
ventricular overload with pulmonary hypertension.


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Internal Medicine 
 
 223Complication of MS 
• Atrial fibrillation 
• Thromboembolism 
• Right sided hear failure  
Echocardiography 
• Echocardiography is the study of choice for diagnosing and assessing the severity of 
mitral stenosis.  
Chest X-ray  may show left atrial enlargement and sign of pulmonary congestions.  
Management  
In asymptomatic patients   
• Annual evaluation (history and physical exam ination, as well as a chest x-ray and 
ECG).  
• Endocarditis prophylaxis 
• Secondary prophylaxis for reumatic fever 
In patients with symptoms : 
Medical treatment 
• Diuretics may be helpful in reducing left atrial pressure and decreasing symptoms.   
• Digoxin: is indicated for patients with atrial fibrillation to control the heart rate, since 
tachycardia will further decrease left ventricular filling, reduce cardiac output and 
increase left atrial pressure, leading to more symptoms.  
• Anticoagulants such as Warferin may be indicated in patients with Left atrium and 
atrial fibrillation. 
Surgical management:  improves survival and reduce symptoms.  
• Open commissurotomy or  
• Mitral valve reconstruction or  
• Mitral valve replacement.  
 
Mitral Regurgitation (MR)  
Causes of chronic mitral regurgitation include: 
• Rheumatic fever 
• Infective endocarditis 
• Degenerative valvular disease (mitral valve prolapsed).  
• Myocardial infarction affecting papillary muscles.


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Internal Medicine 
 
 224Pathophysiology: 
Chronic mitral regurgitation is a state of volume overload leading to the development of left 
ventricular hypertrophy. The left atrium also enl arges to accommodate the regurgitate volume. 
This compensated phase of mitral regurgitation varies in duration but may last many years. The 
prolonged state of volume overload may eventually lead to decompensate mitral regurgitation. This phase is characterized by impaired left ventri cular function, decreased ejection fraction and 
pulmonary congestion.  
The common symptoms are: 
• Fatigue, Exertional dyspnea and orthopnea are the most common complaints. 
• Right sided heart failure with painful hepatic congestion, peripheral edema may occur in 
patients with MR who have associated pulmonary hypertension . 
Physical Examination   
• A soft first heart sound ( S1 is generally absent ) and a widely split second heart sound 
may be present.  
• An S 3 gallop  indicates severe disease but does not necessarily indicate heart failure 
• There may be displacement of the left ventricular impulse 
• A holosystolic murmur that may radiate to the axilla, the upper sternal borders or the 
subscapular region is apparent on physical examination.  
Echocardiography  
• Echocardiography can be used to determine the etiology and morphology of mitral 
regurgitation, which are important in determining suitability for mitral valve repair.


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subscapular region is apparent on physical examination.  
Echocardiography  
• Echocardiography can be used to determine the etiology and morphology of mitral 
regurgitation, which are important in determining suitability for mitral valve repair.  
Chest X-ray : Enlargement of LA and LV , Pulmonary venous congestion and interstitial edema 
and Kerley-B lines .  
Management  
Medical Treatment: 
• Diuretics  
• Digoxin: may be indicated in patients with severe regurgitation and dilated left ventricle 
without frank LV failure. 
• Salt restriction  
• Vasodilators: afterload reduction with vasodilators has been shown to improve left 
ventricular performance.. ACE inhibitors are the preferred vasodilators. 
• Treatment of atrial fibrillation if it occurs  
• Endocarditis prophylaxis is important essential..


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Internal Medicine 
 
 225Surgical Treatment:  Mitral valve replacement  is the definitive treatment.   
• In patients with chronic mitral regurgitation, left ventricular damage can occur while the 
patient remains asymptomatic. Therefore, surgery is indicated if left ventricular 
dysfunction has begun to develop, even in the absence of symptoms. 
• Patents with MR who are asymptomatic  and whose LV function are normal are not 
considered to be candidates for surgical treatment. 
Tricuspid Regurgitation (TR) 
• TR is functional and secondary to marked dilatation of tricuspid annulus The most 
common cause of TR is pulmonary hypertension as result of left sided cardiac failure or pulmonary parenchymal/vascular disease.  
• Less common causes include rheumatic HD, right sides myocardial infarction , and 
endocarditis in IV drug abusers.  
Clinical features  
• In patients with pulmonary HTN symptoms of pulmonary congestion diminish, but the 
symptoms of right sided heart failure are intensified such as peripheral edema and ascites.  
• Patients will have prominent jaguar venous distention  
• Holosystolic murmur at the left lower sternal border.  
• Pulsatile liver and  
• More prominent ascites than edema is a common finding. 
Echocardiography  
• It is a very useful study, and it differentiates primary from secondary TR. 
Management: 
• Treatment of the underlying cause of heart failure usually reduces the severity of 
functional TR.


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Echocardiography  
• It is a very useful study, and it differentiates primary from secondary TR. 
Management: 
• Treatment of the underlying cause of heart failure usually reduces the severity of 
functional TR.  
• Surgical treatment as indicated for primary TR.  
Mitral Valve Prolapse  
• Mitral valve prolapse occurs when varying por tions of one or both leaflets of the mitral 
valve extend or protrude abnormally above the mitral annulus into the left atrium.  
• MVP has different causes 
o Redundant or excessive  mitral valve tissue  
o Congenital diseases such as Marfan’ s syndrome , osteogenesis imperfecta.


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Internal Medicine 
 
 226• Although the prevalence of mitral valve prolapse was once thought to be as high as 15 
percent in the general population, more recent studies using new echocardiographic 
criteria for diagnosis have suggested a prevalence of approximately 2.4 percent.  
Clinical futures  
• MVP is more common in females and more common in the age group of 14-30. 
• The clinical course is often benign 
• Most patients are asymptomatic and may remain so for their entire lives. 
• Some patients may manifest with features of Mitral regurgitation  
• Arrhythmias like premature ventricular contractions and ventricular tacycardias may 
occur as complications. 
• The mid-systolic click, often accompanied by a late systolic murmur, is the auscultatory 
hallmark of mitral valve prolapse.  
Management  
• Asymptomatic patients may need only reassurance 
• Symptomatic patients with thickening of mitral valve  
o Endocarditis prophylaxis is  
o B- blockers sometimes may relive chest pain 
• Sever symptoms from secondary MR: surgical treatment may be needed ( mitral valve 
repair and or rarely replacement. ) 
Summery  
• Even though the definitive management for mo st valvular heart diseases is surgical 
intervention to correct the underlying valvular abnormality ,  in the current Ethiopian 
setup, surgical interventions are not affordable and not available in the country. Hence the general management is treatment of the congestive heart failure state.


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setup, surgical interventions are not affordable and not available in the country. Hence the general management is treatment of the congestive heart failure state.  
• The onset of symptoms in the developing world occurs at an earlier age because of 
repeated attack of recurrent rheumatic fever. Increased left atrial pressure and decreased cardiac output produce the symptom. Therefore both primary and secondary preventions are paramount importance to reduce the morbidity and mortality  
• Great progress has been made in improving rates of morbidity and mortality in patients 
with valvular heart disease. Successful management of patients with valvular heart disease requires an evidence-based approach to echocardiography and to surgical 
intervention.


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Internal Medicine 
 
 227• Echocardiography should assess not only the valvular lesion but also the compensatory 
changes of the heart in response to the lesion.  
• Timing of surgical intervention often correlates with outcome.  
• Most patients with acquired valvular heart disease are at risk for developing endocarditis 
and should receive prophylactic antibiotics.  
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Valvular 
Heart Diseases, pages 1390-1402. 
2. Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition Medicine, 
Valvular Heart Diseases, 29-37.


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Internal Medicine 
 
 2284.  Infective Endocarditis  
 
Learning objectives: at the end of this lesson the student will be able to : 
1) Define valvular heart Infective endocarditis. 2) List the etiologic agents of Infective endocarditis.  3) Describe the different types of Infective endocarditis. 
4) Understand the Epidemiology of Infective endocarditis.  
5) Describe the pathogenesis of Infective endocarditis.  6) Identify the clinical manifestation of Infective endocarditis.  7) Understand the diagnostic approach of Infective endocarditis. 
8) Understand the management of patients having Infective endocarditis .  
 
Definition:  Infective endocarditis (IE) is an infection of the endocardial surface of the heart. The 
intracardiac effects of this infection include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses.  
Infective endocarditis affects not only the heart,  but also produces a wide variety of systemic 
signs and symptoms through several mechanisms, including both sterile and infected emboli 
and a variety of immunological phenomena.  
 
Classification of Infective endocarditis:  depending on the type of valve affected 
1. Native valve endocarditis (NVE) : endocarditis that may develop on natural valve. The 
affected valve may be damaged or normal.  
2. Prosthetic valve endocarditis : is when the endocarditis develops on 
prosthetic/’artificial’ valve. 
3. Endocarditis in intravenous drug abuser (IVDA).


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affected valve may be damaged or normal.  
2. Prosthetic valve endocarditis : is when the endocarditis develops on 
prosthetic/’artificial’ valve. 
3. Endocarditis in intravenous drug abuser (IVDA). 
• There is a marked rise in cases of prosthetic valve endocarditis and endocarditis in IV drug 
abusers in different parts of the world. However Native valve endocarditis is the commonest 
type of Infective endocarditis in Ethiopia and other developing countries. 
• The classic clinical presentation and clinical course of IE has been characterized as either 
acute or subacute.  
o Acute Infective endocarditis :  frequently involves healthy valves. It is a rapidly 
progressive illness with destruction of valvular structures..


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Internal Medicine 
 
 229o Subacute Infective endocarditis : typically affects only previously damaged 
valves. The course is insidious even in untreated cases which may extend over 
many months. 
 Etiologic agent of Infective endocarditis  
• Streptococcus viridans : is a bacterium which is a normal flora of the oral cavity. It 
accounts for approximately 50-60% of cases of subacute infective endocarditis.  
• Group D streptococci:  the source for this bacterium is the gastrointestinal or 
genitourinary tract. Most cases infective endocarditis due to this organism is subacute.  
• S. aureus : is the leading cause of  Prosthetic valve endocarditis (PVE), acute infective 
endocarditis and endocarditis in IVdrug abusers. Approximately 35-60.5% of 
staphylococcal bacteremia is complicated by infective endocarditis. In more than half of 
cases endocarditis due to S. aureus  occurs in the absence of underlying valvular 
disease. Mortality rate may range 40-50% 
• Coagulase-negative S. aureus: it accounts for approximately 30% of PVE cases, fewer 
than 5% of NVE cases. It causes subacute disease  
• HACEK  organisms (i.e., Haemophilus species, Actinobacillus, actinomycetemcomitans, 
Cardiobacterium hominis, Eikenella corrodens, Kingella species ) .These group of 
organisms usually cause subacute disease. It accounts for approximately 5% of infective 
endocarditis. 
• Fungus: Mostly frequently cause subacute disease. Candida albicans  is the commonest 
fungal etiology.


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organisms usually cause subacute disease. It accounts for approximately 5% of infective 
endocarditis. 
• Fungus: Mostly frequently cause subacute disease. Candida albicans  is the commonest 
fungal etiology.  
 Pathophysiology:  
All cases of infective endocarditis deve lop from a commonly shared process:  
1. Bacteremia (nosocomial or spontaneous) that  delivers the organisms to the valve's 
surface 
2. Adherence of the organisms to valvular structures 
3. Eventual invasion of the valvular leaflets and formation of vegetations.  
• Infective endocarditis develops most commonly on the mitral valve, closely followed in 
descending order of frequency by the aortic valve, the combined mitral and aortic valve, the tricuspid valve, and, rarely, the pulmonic va lve. Mechanical prosthetic and bioprosthetic 
valves exhibit equal rates of infection.


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Internal Medicine 
 
 230• Turbulence in blood flow damages valvular surface and edocardium which creates a 
favorable situation for formation of sterile thrombus (vegetation) made of platelets and fibrin. 
• The microorganisms that most commonly produce endocarditis (i.e., S. aureus; S.viridans;  
group A, C, and Group D streptococci; enterococci) resist the bactericidal action of 
complement and possess fibronectin receptors for the surface of the fibrin and platelet 
thrombus.  
• Either a spontaneous bacteremia or one that is the result of an invasive procedure gives 
access to the bacteria to adhere to the sterile platelet/fibrin vegetation. Most cases of subacute disease are secondary to the bactermias that develop from the activities of daily living (e.g., brushing teeth, bowel movements) 
• The complications of acute bacterial endocarditis result from intracardiac disease and 
metastatic infection produced by suppurative emboli. Because of their shortened course, 
immunological phenomena are not a part of acute infective endocarditis.  
 
Clinical Features  
A. Subacute infective endocarditis 
• The patient suspected of SBE should be asked about invasive procedures that may be 
causing bacteremia. Most subacute disease caused by S.viridans  is related to dental 
disease.  
• The symptoms of early subacute NVE usually are subtle and nonspecific.  
• SBE is suggested by a history of a slowly pr ogressive process characterized by fever,


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disease.  
• The symptoms of early subacute NVE usually are subtle and nonspecific.  
• SBE is suggested by a history of a slowly pr ogressive process characterized by fever, 
fatigue, anorexia, back pain, and weight loss.  
• Less common developments are a cerebrovascu lar accident or congestive heart failure.  
• When appropriate therapy is delayed for weeks or months, additional clinical features, 
embolic or immunological in origin, develop. 
 
Embolic manifestations of infective endocarditis include: 
o Acute meningitis with sterile spinal fluid 
o Hemiplegia due to embolization in the distribution of the middle cerebral artery 
o Renal regional infarcts producing painless hematuria 
o Splenic infarction   
o Unilateral blindness caused by occlusion of a retinal artery 
o Myocardial infarction resulting from embolization to a coronary artery.


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Internal Medicine 
 
 231The risk of embolization is related to the type of the organism, the size of the vegetation and its 
rate of growth or resolution, and the location of the vegetation. 
Immunologic Manifestations of SBE: 
o Acute glomerulonephritis 
o Osler’s nodes  
o Roth spots  
o Presence of rheumatoid factor 
 
Common Physical findings in SBE 
• Fever:   most patients have low grade fever; however 3-15% of patients with SBE may 
have normal or subnormal temperature.  
• Murmurs : the vast majority of patients have detectable heart murmurs (99% of cases). 
The absence of a murmur should cause clinicians to reconsider the diagnosis of IE. The 
major exception is right-sided infective endocarditis, in which only one third of cases 
have a detectable murmur.  
• The peripheral lesions of subacute infective endocarditis  are observed in only 
approximately 20% of patients as compared to 85% in the preantibiotic era. 
o Petechiae  are the most common peripheral lesions. They may occur on the 
palpebral conjunctivae, the dorsa of the hands and feet, the anterior chest and abdominal walls, the oral mucosa, and the soft palate. 
o Subungual hemorrhages  (i.e., splinter hemorrhages) are linear and red lesions 
that do not extend for the entire length of the nail. 
o Clubbing of fingers and toes  may be seen. It primarily occurs in those patients 
who have an extended course of untreated infective endocarditis.


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that do not extend for the entire length of the nail. 
o Clubbing of fingers and toes  may be seen. It primarily occurs in those patients 
who have an extended course of untreated infective endocarditis. 
o Arthritis  associated with subacute infective endocarditis is asymmetrical and 
limited to 1-3 joints.  
o Splenomegaly  is observed more commonly in patients with long-standing 
subacute disease. It may persist long after successful therapy. 
o Osler nodes  are small tender nodules that range in color from red to purple and 
are located primarily in the pulp spaces of the terminal phalanges of the fingers and toes, soles of the feet, and the thenar and hypothenar eminences of the hands. 
B. Acute infective endocarditis: 
• History of antecedent procedures or illicit drug use must be investigated.


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Internal Medicine 
 
 232• Is a much more aggressive disease. The onset of illness is abrupt, with rapidly 
progressive destruction of the infected valve. The valvular leaflets are destroyed rapidly 
by bacteria that multiply very fast  within the ever-growing friable vegetations.  
• The clinical symptoms of acute infective endocarditis result from either embolic or 
intracardiac suppurative complications.  
• There is an acute onset of high-grade fever and chills and a rapid onset of congestive 
heart failure.  
• Complications develop within a week. These include the dyspnea and fatigue of severe 
congestive heart failure and a wide spectrum of neuropsychiatric complications resulting from involvement of the CNS. 
• Roth spots  are retinal hemorrhages with pale centers. The Litten sign represents 
cotton-wool exudates. 
• Murmurs  are present in nearly two third of patients with acute infective endocarditis. 
The most common type is murmur aortic regurgitation. Because of the rapid onset, the left ventricle does not have a chance to dilate. In this situation, the classic findings of increased pulse pressure that are seen in chronic AR are absent. 
• Janeway lesions  are irregular erythematous and painless macules (1-4 mm in 
diameter). They most often are located on the thenar and hypothenar eminences of the hands and feet. They usually represent an infectious vasculitis of acute infective 
endocarditis resulting from S.  aureus  infection.


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diameter). They most often are located on the thenar and hypothenar eminences of the hands and feet. They usually represent an infectious vasculitis of acute infective 
endocarditis resulting from S.  aureus  infection. 
• Acute septic monoarticular arthritis  in patients with acute infective endocarditis most 
often is caused by S aureus  infection. 
• Purulent meningitis  may be observed in patients with acute infective endocarditis , as 
compared to the aseptic type observed in patients with subacute disease.  
C. Right-sided infective endocarditis:  is associated with a very low rate of congestive heart 
failure and valvular perforation.   
o Pulmonary infarcts may result from emboli of right-sided infective endocarditis


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Internal Medicine 
 
 233   Table III-4-1: Frequencies of Occurrence of prominent Clinical and Laboratory 
Manifestations in Endocarditis 
 
Clinical manifestations % of occurrence  
Fever 
Arthralgias and/or myalgias Murmur 
Splenomegaly 
Splinter hemorrhages Roth's spots Osler's nodes Janeway lesions 
Clubbing 
Clinically apparent emboli Neurologic manifestations > 95 25-45 > 85 
25-60 
20-40 < 5 10-25 < 5 
10-20 
25-45 20-40 
LABORATORY MANIFESTATIONS   
Anemia Leukocytosis Proteinuria Microscopic hematuria Elevated serum creatinine level 
Elevated erythrocyte sedimentation rate 
Rheumatoid factor Circulating immune complexes Decreased serum complement level 70-90 20-30 50-65 30-50 10-20 
>90 
50 65-100 5-40              
 
Diagnostic work up:  
Lab Studies:  
1. Blood Culture :  
• The gold standard test for the diagnosis of infective endocarditis is the 
documentation of a continuous bacteremia (>30 min in duration) through  blood 
culture.


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Internal Medicine 
 
 234• For making diagnosing SBE draw 3-5 sets of blood cultures , at 3 different sites ,  
over 24 hours.  
• This detects 92-98% of cases in patients who have not received antibiotics 
recently.  
• In the case of Acute infective endocarditis, 3 sets may be drawn over 30 minutes 
(with separate venipunctures) to document a continuous bacteremia. 
2. Echocardiography 
• Has become the indirect diagnostic method of choice, especially in patients who 
present with a clinical picture of infective endocarditis but who have 
nondiagnostic blood cultures. 
• The diagnosis of infective endocarditis can never be excluded by a negative 
echocardiogram. 
3. Other Tests:  
• Electrocardiography  may detect the 10% of patients who develop a conduction 
delay during infective endocarditis by documenting an increasing P-R interval. 
Rheumatoid factor  becomes positive in 50% of patients with subacute disease. It becomes 
negative after successful treatment.   
  Table III -4-2. The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis  
 Major Criteria 
1. Positive blood culture:   for typical microorganism that causes infective 
endocarditis from two separate blood cultures.  ( Viridans streptococci , 
Streptococcus bovis , HACEK group , or Community-acquired Staphylococcus 
aureus  or enterococci in the absence of a primary focus ) 
2. Positive echocardiogram :  
• Definitive vegetation ( oscillating intracardiac mass on valve or supporting


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Streptococcus bovis , HACEK group , or Community-acquired Staphylococcus 
aureus  or enterococci in the absence of a primary focus ) 
2. Positive echocardiogram :  
• Definitive vegetation ( oscillating intracardiac mass on valve or supporting 
structures )  
• Abscess   
• New partial dehiscence of prosthetic valve   
• New valvular regurgitation (increase or change in preexisting murmur not 
sufficient)


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 235 
Minor Criteria 
• Predisposition : predisposing heart condition or IV drug abuse  
• Fever >38.0 oC. 
• Embolic  phenomena : major arterial emboli, septic pulmonary infarcts, mycotic 
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions 
• Immunologic phenomena : glomerulonephritis, Osler's nodes, Roth's spots, 
rheumatoid factor 
• Microbiologic evidence : positive blood culture but not meeting major criterion.  
Echocardiogram : consistent with infective endocarditis but not meeting major 
criterion 
SOURCE: Adapted from Durack et al. 
 
Definitive Diagnosis can be made by documentation of: 
• Two major criteria or 
• One major and three minor criteria or  
• Five minor criteria allows a clinical diagnosis of definite endocarditis.  
Treatment: 
All patients should be treated in the hospital to allow adequate monitoring of the development of 
complications and the response to the antibiotic therapy. 
General measures: 
• Diet: No special diets are recommended for patients with endocarditis; however, if the 
patient has congestive heart failure, sodium-restriction may be necessary.  
• Activity: Activity limitations are determined by the se verity of illness, complications (e.g., 
stroke), and the presence of significant congestive heart failure.  
Medical  Treatment  
The major goals of therapy for infective endocarditis are  
• Eradicating the infectious agent from the thrombus


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stroke), and the presence of significant congestive heart failure.  
Medical  Treatment  
The major goals of therapy for infective endocarditis are  
• Eradicating the infectious agent from the thrombus  
• Treating the complications of valvular infection 
1. Eradicating the infectious agent from the thrombus  
• Antibiotics remain the mainstay of treatment for IE. In the setting of acute IE, 
antibiotic therapy should be instituted as soon as possible to minimize valvular


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 236damage. Three to five sets of blood cultures should be obtained within 60-90 
minutes, followed by the infusion of the appropriate antibiotic regimen.  
• By necessity, the initial antibiotic choice is empiric, determined by clinical history and 
physical examination. 
• In the case of subacute IE, treatment may be safely delayed until cultures and 
sensitivities are available. Waiting does not increase the risk of complications in this form of the disease. 
• Eradicating bacteria from the fibrin-platelet thrombus is extremely difficult..  
• Intravenous administration is the preferred to ensure reliable serum therapeutic 
levels.  
• The antibiotics should be bactericidal and are should be administered at higher dose 
for prolonged period of time. 
 
Empirical antibiotic treatment  
NVE of sub acute nature:  
• Crystalline penicillin 3-4 million IU IV every 4 hours for 4- 6 weeks plus 
• Gentamicin 1mg/kg ( 80 mg ) IV TID for 2 weeks plus  
Prosthetic Valve endocarditis: 
• Vancomycin 1gm IV BID  for 6 weeks Plus  
• Gentamicin 1mg/kg ( 80 mg ) IV TID for 2 weeks plus 
• Refampicin 300 mg PO /TID for 6 weeks  
Acute Infective endocarditis where S.aureus is suspected : E.g. hospital acquired infection    
• Naficillin 1.5-2gm IV every 4 hours OR Vancomycin 1gm IV BID  for 6 weeks  Plus  
• Gentamicin 1mg/kg (80 mg) IV TID for 2 weeks.


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Acute Infective endocarditis where S.aureus is suspected : E.g. hospital acquired infection    
• Naficillin 1.5-2gm IV every 4 hours OR Vancomycin 1gm IV BID  for 6 weeks  Plus  
• Gentamicin 1mg/kg (80 mg) IV TID for 2 weeks. 
When the result of blood culture is made available the choice of antibiotics depend on the type of organism identified and the anti microbial sensitivity. 
2. Dealing with the complications of valvular infection. The latter includes both the intracardiac and extracardiac consequences of infective endocarditis.  
• Mild congestive heart failure resulting from valvular insufficiency or myocarditis may be 
managed with standard medical therapy for CHF.  
• Although thrombosis is a key element of infective endocarditis, anticoagulation with 
heparin or Warfarin is controversial, and it should be avoided. 
 Surgical Treatment:  Approximately 15-25% of patients with IE eventually require surgery.


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 237Indication for Surgery: 
• Acute AR with severe Heart failure  
• Fungal endocarditis 
• Mobile vegetation > 10mm in size.  
• Evidence of valve ring or myocardial abscess 
• Recurrent embolization despite adequate antibiotic therapy 
• Poor response to antibiotics 
• Prosthetic valve dysfunction  associated with CHF 
• Valve ring Abscess near a prosthetic valve  
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  Infective 
endocarditis , pages 731-739.


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Internal Medicine 
 
 2385. Cardiomyopathy  
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Cardiomyopathy. 2. List the etiologies of Cardiomyopathies.  3. Describe the different types of Cardiomyopathies. 
4. Understand the Epidemiology of Cardiomyopathies.  
5. Describe the pathogenesis of Cardiomyopathies.  6. Identify the clinical manifestation of Cardiomyopathies.  7. Understand the diagnostic approach of Cardiomyopathies. 8. Understand the management of patients Cardiomyopathies. 
 Definition:  
Cardiomyopathies are a group of diseases that affect the myocardium and are not the result of 
hypertension, valvular, coronary or pericardial abnormalities. Cardiomyopathies are frequently 
associated with myocardial dysfunction and su bsequently heart failure. With few exceptions, 
histologic findings are nonspecific, with myoc yte hypertrophy, cellular necrosis, and fibrosis. 
 
Etiologic classification of Cardiomyopathies: 
Primary Myocardial Involvement 
• Idiopathic  
• Familial 
• Eosinophilic  endomyocardial diseases 
• Endomyocardial Fibrosis 
Secondary myocardial involvement: 
• Infective Myocarditis: Viral , bacterial , fungal , protozoal , Metazoal , Spirochetal 
• Metabolic : Thyrotoxicosis 
• Familial storage diseases: Glycogen storage diseases , Hemochromatosis ,  
• Deficiencies : Electrolyte  , Nutritional ( Vitamin B 1 deficiency )  
• Connective tissue diseases : SLE , polyarteritis nodosa , Rheumatoid arthritis ,


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• Familial storage diseases: Glycogen storage diseases , Hemochromatosis ,  
• Deficiencies : Electrolyte  , Nutritional ( Vitamin B 1 deficiency )  
• Connective tissue diseases : SLE , polyarteritis nodosa , Rheumatoid arthritis , 
Systemic sclerosis  
• Infiltration and granulomas ; Amyloidosis , sarcoidosis , malignancies  
• Neuromuscular : muscular dystrophies ,myotonic dystrophies


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 239• Sensitivity and toxic reactions : Alcohol , drugs , radiation   
• Peripartum heart diseases  
 
Table III-5-1 Clinical classification of Cardiomyopathies 
DISORDER  DESCRIPTION  
Dilated cardiomyopathy  Dilatation and impaired contraction of the left or both ventricles. 
Caused by familial/genetic, viral and/or immune, alcoholic/toxic, or unknown factors, or is associated with recognized cardiovascular disease.  
Hypertrophic cardiomyopathy  Left and/or right ventricular hypertrophy, often asymmetrical, which usually involves the interventricular septum. Mutations in sarcoplasmic proteins cause the disease in many patients.  
Restrictive 
cardiomyopathy  Restricted filling and reduced diastolic size of either or both ventricles with normal or near-normal systolic function. Is 
idiopathic or associated with other disease (e.g., amyloidosis, endomyocardial disease).


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 2405.1 Dilated  Cardiomyopathy   
 
Definition  
• This condition may be defined as impaired left and/or right ventricular systolic 
dysfunction characterized by an ejection fraction <40% in the presence of increased left ventricular dimensions (left ventricular end-di astolic size >115% of that calculated for 
age and body surface area).  
Pathophysiology   
• Dilated cardiomyopathy represents the final common morphologic outcome of a variety 
of biological insults. It is a combination of myocyte apoptosis and necrosis with 
increased myocardial fibrosis, producing reduced mechanical function. Many causes are a result of direct toxicity (e.g., alcohol) or mechanical insults (e.g., chronic volume 
overload in mitral valvular regurgitation), infection (eg myocarditis).  
Clinical manifestations  
• A careful history is essential , with particular emphasis on  
o Family history of similar illness  
o Exposure to cardio toxins such as alcohol 
o Protracted "flu-like illness" or respiratory tract infection may suggest previous 
myocarditis 
o History of recent delivery or being in the last trimester of pregnancy  
• Some patients may have left ventricular dilatation for months or even years and may 
remain asymptomatic and are diagnosed only by screening or postmortem examination.  
• Symptoms of left and right sided congestive heart failure develop gradually in most 
patients. Unfortunately, the most common clinical presentation is one of progressive


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• Symptoms of left and right sided congestive heart failure develop gradually in most 
patients. Unfortunately, the most common clinical presentation is one of progressive 
deterioration, with worsening heart failure and death occurring over a variable time 
course. 
• Syncope may result from arrhythmias  
• Systemic embolization, often emanating from ventricular thrombus, may occur. 
 
Physical examination :  
• Hypotension , tachycardia  
• Cardiomegaly ( displaced PMI ) 
• Findings of CHF : narrow pulse pressure , raised JVP and S
3 and S 4 gallops


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 241• Functional mitral or tricuspid regurgitation. 
Diagnostic work up: 
• Chest radiograph : enlargement of cardiac silhouette and evidence of pulmonary 
congestion 
• ECG : sinus tachycardia or atrial fibrillation , , ventricular arrhythmias, St segment and T 
wave abnormalities  
• Echocardiogram:  Left ventricular dilatation and dysfunction (ejection fraction < 40 %) 
• Other laboratory investigation include  
o Complete blood cell count  
o Renal function test  
o Blood glucose ( fasting or random) 
o Lipid profile  glucose 
o Thyroid function tests  
 
Treatment of Dilated Cardiomyopathy 
Medical Therapy : Standard therapy of heart failure  
• Salt restriction 
• Diuretics  
• Digitalis 
• ACE inhibitors or Angiotensin II receptor blockers  
• Spirinolactone  
• Alcohol should be avoided 
• Identify and treat the underlying cause if it is treatable  
Surgical Therapy : Cardiac transplantation provides a medi an 10-year survival and is effective 
palliation in appropriately selected individuals. 
Prognosis. 
• In the absence of a specific remediable etiology (e.g., in peripartum cardiomyopathy, 
alcoholic cardiomyopathy, ischemic hibernat ing revascularizable myocardium), the 
overall outcome is poor in patients with cardiomyopathy. 
• Majority of patients have downhill course, and particularly those >55 years, die within 3 
years of onset of symptoms. The 5-year survival rate of patients diagnosed with heart 
failure is 50%.


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• Majority of patients have downhill course, and particularly those >55 years, die within 3 
years of onset of symptoms. The 5-year survival rate of patients diagnosed with heart 
failure is 50%. 
• Blacks are more likely to suffer progressive heart failure and death than whites


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Internal Medicine 
 
 2425.2 Hypertrophic Cardiomyopathy   
 
Definition:  
Hypertrophic cardiomyopathy is characterized by left ventricular hypertrophy (myocardial 
thickness greater than 1.5 cm), typically of none dilated chamber, without obvious causes. Other 
etiologies of left ventricular hypertrophy, such  as long-standing hypertension and aortic stenosis 
need to be excluded before one can diagnose HCM.   
 
Genetic Predisposition: 
• HCM is the most common genetic cardiovascular disease. About half of patients with 
HCM have a positive family history wi th autosomal dominant transmission. 
• The prevalence in the general adult population for people with phenotypic evidence of 
HCM is estimated at 1 per 500.  
 Pathophysiology:  
Generally, ventricular hypertrophy involves the pr oximal portion of the interventricular septum. 
As the septum thickens, it may narrow the outflow tract. In addition, systolic anterior motion of the mitral valve may occur and result in left ventricular outflow tract obstruction and mitral regurgitation. When systolic anterior motion occurs, the mitral valve leaflets are pulled or dragged anteriorly toward the ventricular septum, producing the obstruction. Consequently, the left ventricle has to generate much higher pressu res to overcome the out flow  obstruction and 
to pump blood to the systemic circulation. Prem ature closure of the aortic valve may occur and


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to pump blood to the systemic circulation. Prem ature closure of the aortic valve may occur and 
is caused by the decline in pressure distal to the left ventricular outflow obstruction.  
 Clinical Features  
• The clinical course of HCM is variable. Most patients with HCM are asymptomatic.  
• The most common symptom of HCM is dyspnea on exertion.  
• Patients may also complain of chest pain with exertion, syncope or near syncope, or 
palpitations.. Congestive heart failure and atrial fibrillation along with their accompanying symptoms may be part of the natural history of HCM.  
• Unfortunately, the first clinical manifestation of the diseases may be sudden cardiac 
death frequently occurring in young children and young adults. , often during or after 
physical exertion.


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 243Physical examination : 
• Unless congestive heart failure has developed, the lungs are usually clear and the 
jugular venous pressure normal 
• Bisferiens pulse : rapidly rising carotid pulse followed by a collapse in the pulse and 
then a secondary rise. 
• The point of maximal impulse may be double or triple, forceful and sustained.  
• S4 gallop  may be present.  
• Systolic murmur : the classic auscultatory finding for HCM is a crescendo-decrescendo 
systolic murmur along the left sternal border t hat increases with the Valsalva maneuver. 
In young adults, HCM is the most common etiology for sudden cardiac death. 
Diagnosis  
Laboratory studies generally will be unremarkable.  
• Chest radiograph  may suggest left ventricular hypertrophy but will often be normal 
because the hypertrophy in HCM involves the ventricular septum.  
• The electrocardiogram  often shows left ventricular hypertrophy and occasionally may 
also have a pseudoinfarct pattern.   Left atrial abnormality may be present if the patient 
has had long-standing mitral regurgitation from systolic anterior motion of the mitral valve. Atrial fibrillation also may be present as one of the complications of HCM. 
• Echocardiography  is the gold standard for diagnosing HCM. On transthoracic 
echocardiography, the clinician should note the thickness of the septum; location and pattern of hypertrophy; site and degree of left ventricular outflow tract obstruction;


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echocardiography, the clinician should note the thickness of the septum; location and pattern of hypertrophy; site and degree of left ventricular outflow tract obstruction; 
presence of systolic anterior motion of the mitral valve; presence of premature closure of 
the aortic valve; and any change in severity of obstruction with amyl nitrite 
Treatment:  
Medical Therapy 
• Competitive sport and probably str enuous exercise should be avoided. 
• Dehydration should be avoided and diuretics should be used with caution. 
• ß-blockers are considered first-line therapy. By decreasing contractile force, ß-blockers 
decrease the outflow gradient and decrease oxygen demand. ß-blockers also lengthen diastolic filling by slowing the heart rates. They help to control chest pain. 
• Calcium channel blocker: Second-line therapy includes the verapamil and, Diltiazem can 
be used. But Nifedipine, amlodipine and felodipine should be avoided because they


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Internal Medicine 
 
 244cause peripheral vasodilatation, which may result in decreased left ventricular filling and 
worsening of symptoms of outflow tract obstruction. 
• Atrial fibrillation is a common complicati on of HCM. Treatment of persistent atrial 
fibrillation in HCM includes anticoagulation and rate control, preferably with ß-blockers. 
• Digoxin should be avoided in HCM patients, part icularly in those with resting or latent 
obstruction, because of its positive inotropic effect.  
• Patients with HCM should receive prophylactic antibiotics for endocarditis prevention 
before dental or invasive procedures. Turbulent flow through the LVOT striking the aortic 
valve as well as mitral regurgitation from systolic anterior motion of the mitral valve 
predispose to endocarditis. 
Surgical Therapy 
• Septal myomectomy/myotomy may cause lasting symptomatic relief in ¾ of severely 
symptomatic patients. 
• Alcohol ablation: ethanol injection in to the septal artery has also been reported to 
reduce obstruction. 
Prevention : First degree relatives of patients with HCM should be screened with ECHO.


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 245Restrictive Cardiomyopathy  
Definition  
• Restrictive cardiomyopathy is a disease of  the myocardium that is characterized by 
restrictive filling and reduced diastolic volume of either or both ventricles with normal or 
near-normal systolic function.  
 Pathophysiology: 
These conditions result in impaired ventricular filling and primarily diastolic heart failure. They 
present with a clinical heart failure syndrome t hat is frequently indistinguishable from that 
caused by systolic dysfunction. Atrial fibrillation is poorly tolerated. It simulates other right side heart failure like cor pulmanale and diastolic dysfunction of constricted pericarditis.  
Clinical Features
: 
• Exercise intolerance and dyspnea are the prominent symptoms. 
• Peripheral edema with predominant ascites  
• Enlarged tender and pulsatile liver. 
• JVP is elevated and it doesn’t fall norma lly during inspiration ( Kussmaul’s sign ) 
• The heart sounds may be distant but apica l impulse is easily palpable unlike in 
constrictive pericarditis. 
Differential Diagnosis : The clinical features are very similar to constrictive pericarditis.  
Diagnostic work up 
• Chest x-ray : mild cardiac enlargement   
• ECG: low voltage and conduction defects   
• Echocardiography: Increases left ventricular wall thickness, normal or mildly reduced 
systolic function.


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Internal Medicine 
 
 2466. Myocarditis  
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Myocarditis. . 
2. List the etiologies of Myocarditis. 3. Describe the different types of Myocarditis. 
4. Understand the epidemiology of Myocarditis. 
5. Understand the pathophysiology of Myocarditis. 6. Identify the clinical manifestation of Myocarditis. 7. Identity consequences of Myocarditis.  8. Understand the diagnostic approach of Myocarditis. 
9. Understand the principle of management of Myocarditis.  
 
Definition:  Myocarditis is inflammation of the myocardium often resulting from infectious 
process, which subsequently leads to myocardi al destruction and a dilated cardiomyopathy.  
The acute picture is nonspecific unless overt congestive heart failure develops. Although the 
causes of myocarditis are numerous, the most common association is an antecedent viral 
syndrome.   
Etiologies of Myocarditis  
1. Infectious causes 
• Viral infections : Coxsackievirus B , HIV myocarditis ( overt involvement is seen 
in 10 % of HIV patients ) 
• Bacterial myocarditis:  
o Not common usually occurs as a complication of infective endocarditis. 
o Diphtheric myocarditis may develop in ¼ of patients with diphtheria 
• Fungal myocarditis 
• Protozoal myocarditis: Chaga’s dis ease caused by a protozoon Trypanosoma 
cruzi and transmitted by an insect vector. It is one of the most common causes of 
heart disease in Central and South America.


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• Fungal myocarditis 
• Protozoal myocarditis: Chaga’s dis ease caused by a protozoon Trypanosoma 
cruzi and transmitted by an insect vector. It is one of the most common causes of 
heart disease in Central and South America. 
• Rickettsial myocarditis :associated with Typhus , Lyme disease 
• Spirocheatal myocarditis: associated with Relapsing fever.


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 2472. Hypersensitivity and toxic reactions to : 
• Drugs : Doxorubicin ( anti- neoplastic agent )  
• Radiation 
3. Giant cell myocarditis  : is a rare form of myocarditis of unknown etiology 
 
Pathophysiology:   
Myocarditis is defined as inflammatory changes in the heart muscle and is characterized by an 
interstitial mononuclear cell infiltrate with an attendant myocyte necrosis.  It is not known whether the infiltrate is caused by a direct invasion of the infective agents or by a systemic immune response. In the chronic stage, cytotoxic T lymphocytes infiltrate the myocardium and mediate an autoimmune response with myocardial autoantibody activity 
directed against cardiac myosin. This autoimmune process persists after the viral particles are no longer detected. Coronary artery thrombus formation, luminal obstruction, ischemia, and dysrhythmias compound the deleterious effects of the inflammatory response.  
 
Clinical features   
• The clinical presentation of myocarditis is variable. Patients may present with a 
nonspecific illness characterized by fatigue, mild dyspnea, or fulminant congestive heart 
failure (CHF). Myocarditis may even cause sudden death in some patients. 
• The majority of cases of myocarditis are subclinical; therefore, the patient rarely seeks 
medical attention during acute illness. 
• An antecedent viral syndrome has been documented in 60% of patients with


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• The majority of cases of myocarditis are subclinical; therefore, the patient rarely seeks 
medical attention during acute illness. 
• An antecedent viral syndrome has been documented in 60% of patients with 
myocarditis. The typical time interval between the onset of the viral illness and cardiac 
involvement is 2 weeks. 
• Fever is present in 20% of cases. Fatigue , myalgia and,malaise are common symptoms  
• Chest pain or chest discomfort is reported in 35% of cases. The chest pain is often 
pleuritic quality with precordial pain of a sharp stabbing nature. Sometimes it may be substernal and squeezing, more typical of ischemic pain. 
• Dyspnea on exertion is common and orthopnea and shortness of breath at rest may be 
noted if CHF is present. 
• Palpitations are common.  
• Syncope signals development of AV block or malignant dysrhythmias and may lead to 
sudden death in patients with myocarditis.


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 248Physical examination :  
• Patients with mild cases of myocardi tis have a nontoxic appearance and simply may 
appear to have a viral syndrome. Tachypnea and tachycardia are common. Tachycardia 
is often out of proportion to fever. 
• More acutely ill patients have signs of left ventricular failure including:  
o Raised JVP, bilateral basal crepitations on the chest, ascites and pperipheral 
edema. S 3 gallop may be noted with significant cardiac enlargement (displaced 
apical impulse). S 1 is soft or muffled. Cyanosis may be noticed. 
o Hypotension caused by left ventricular dysfunction is uncommon in the acute 
setting. A poor prognosis is indicated when hypotension is present. 
o Cardiogenic shock is observed in fulminant cases and has a high mortality. 
o Murmurs of mitral or tricuspid regurgitation may be present due to ventricular 
dilation. 
• In cases where a dilated cardiomyopathy has developed, signs of peripheral or 
pulmonary thromboembolism may be found. 
• Associated pericarditis may manifest with a per icardial friction rub. Pericardial effusion is 
common, but signs of tamponade (e.g., hypotension, jugular venous distention, muffled heart sounds) are rare. 
• Pleural friction rub might be heard because pleuritis can occur with cases of acute 
myocarditis. 
               
Diagnostic workup  
Since many cases of myocarditis are not clin ically obvious, a high degree of suspicion is


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• Pleural friction rub might be heard because pleuritis can occur with cases of acute 
myocarditis. 
               
Diagnostic workup  
Since many cases of myocarditis are not clin ically obvious, a high degree of suspicion is 
required for the making a diagnosis of acute myocarditis.  
Laboratory Studies:  
• Erythrocyte sedimentation rate (ESR) is elevated in 60% of patients with acute 
myocarditis. 
• Leucocytosis is present in 25% of cases. 
Imaging Studies:


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 249• Chest x-ray: often reveals a normal cardiac silhouette, but pericarditis or overt clinical 
CHF may be associated with cardiomegaly. Vascular redistribution, interstitial and 
alveolar edema and pleural effusion may also be noticed.  
• Echocardiography: Dilated chambers and reduced ejection fraction indicating left 
ventricular systolic dysfunction. 
• ECG:  Sinus tachycardia is the most frequent finding. ST-segment elevation without 
reciprocal depression, particularly when diffuse, is helpful in differentiating myocarditis 
from acute myocardial infarction 
Treatment of Myocarditis  
• Patients with mild symptoms and no signs of cardiac failure or dysrhythmia may be 
treated on an outpatient basis.  
• The medical treatment of myocarditis is directed towards amelioration of associated 
complications including CHF and cardiogenic shock, arrhythmias, and 
thromboembolism. 
1. Left ventricular dysfunction with signs of CHF should be treated with; 
• Low sodium diet 
• Limitation or avoidance of exercise as exercise may have deleterious effect. 
• Diuretics 
• Digoxin: should be given with caution as patients with myocarditis are 
sensitive for digitalis toxicities. 
• ACE inhibitors and vasodilators 
• In general, sympathomimetic and beta-blocker drugs should be avoided 
because they increase the extent of myocardial necrosis and mortality. 
2. Arrhythmias :  
• Detection of dysrhythmia with inpatient cardiac monitoring.


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• In general, sympathomimetic and beta-blocker drugs should be avoided 
because they increase the extent of myocardial necrosis and mortality. 
2. Arrhythmias :  
• Detection of dysrhythmia with inpatient cardiac monitoring.  
• Medical therapy for arrhythmias  
• Implantation of cardiac pacemakers. 
3. Avoiding risk of thromboembolism:;  
• Anticoagulants such as Warfarin or Heparin may be given. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in the 
early course of disease because of inhibition of prostaglandin production, worsened myocyte function, and increased myocardial necrosis.


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 250Prognosis:  
• Majority of cases are believed to be clinically silent and resolve spontaneously 
without sequelae; therefore, it is difficult to make accurate statements concerning 
the prognosis of myocarditis. 
• Patients presenting with CHF experience morbidity and mortality based on the 
degree of left ventricular dysfunction, and the presence of arrhythmias and thromboemblic complications increase the risk of mortality from myocarditis. 
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Cardiomyopathy and Myocarditis,  pages 1408-1413. 
2. Myers R. Allen , National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Cardiomyopathies , pages 38-43


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 2517. Hypertension.  
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Hypertension. 
2. List the etiologies of Hypertension. 3. Describe the different types of Hypertension. 
4. Understand the epidemiology of Hypertension. 
5. Understand the pathophysiology of Hypertension. 6. Identify the clinical manifestation of Hypertension. 7. Identity consequences of Hypertension.  8. Understand the diagnostic approach of Hypertension. 
9. Understand the management of chronic hypertension and hypertensive crisis.  
 
Definition: 
• Hypertension is defined as arterial blood pressure that exceeds 140/90mmHg at several 
determinations. This is an arbitrary definitio n because a diastolic pressure of even 85 
mm Hg may be associated with increased cardiovascular morbidity and mortality. 
• Hypertension is one of the most common diseases afflicting humans throughout the 
world. Because of the associated morbidity and mortality and the cost to society, hypertension is an important public health challenge.  
• It is easily detectable, usually easily treatable, and often leads to lethal complications if 
left untreated. 
• Hypertension is the most important modifiable risk factor for coronary heart disease,


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• It is easily detectable, usually easily treatable, and often leads to lethal complications if 
left untreated. 
• Hypertension is the most important modifiable risk factor for coronary heart disease, 
stroke, congestive heart failure, end-stage renal disease, and peripheral vascular disease. Therefore, health care professionals must not only identify and treat patients with hypertension but also promote a healthy lifestyle and preventive strategies to decrease the prevalence of hypertension in the general population.  
Epidemiology  
• Overall, approximately 20% of the world's adults are estimated to have hypertension in 
excess of 140/90 mm Hg. Some studies done in developed countries show almost 50 % 
of the population may have hypertension.  
• The prevalence dramatically increases  in patients older than 60 years.  
• The prevalence is higher among balks than whites.


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 252• The age-adjusted prevalence of hypertension is slightly higher in men than in women. 
The prevalence in women is closely related to age, with substantial increase occurring 
after age 50. This may be related to hormonal changes associated with menopause. 
• There is paucity of data about prevalence of hypertension in Ethiopia , however some 
studies have shown  that 6% of adolescent and young adults in urban area may have hypertension, and 11% of immigrant from Ethiopia to Israel ,  after 2- 4 years of stay were found to have developed hypertension 
 
Classification  
Because the risk to an individual patient may correlate with the severity of hypertension, a classification system is essential for making decisions about aggressiveness of treatment or 
therapeutic interventions. 
 
Table III-7-1. Classification of blood pressure for adults and older children * 
 
   
BLOOD PRESSURE ( in mm Hg)  
CATEGORY  Systolic   Diastolic  
Optimal <120  and  <80  
Normal  <130  and  <85  
High-normal  130–139 or  85–89  
 
Hypertension   
Stage 1  140–159 or  90–99  
Stage 2  160–179 or  100–109  
Stage 3  
 180  or  N 
 110  
 
• When systolic and diastolic blood pressure levels fall into different categories, the 
higher category should be selected to classify the individual's blood pressure status.  
E.g.       160/92 mm Hg should be classified as stage 2 hypertension 
 174/120 mm Hg should be classified as stage 3 hypertension.


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 253• Isolated systolic hypertension is defined as systolic blood pressure 140 mm Hg or 
greater and diastolic blood pressure le ss than 90 mm Hg and staged approximately 
(e.g., 170/82 mm Hg is defined as stage 2 isolated systolic hypertension).  
• In addition to classifying stages of hypertension on the basis of average blood 
pressure levels, clinicians should specify the presence or absence of target organ 
damage and additional risk factors. This specificity is important for risk classification and treatment. 
• Optimal blood pressure with respect to cardiovascular risk is ≤ 120/80 mm Hg.  
• Hypertension should be diagnosed based on the average of two or more readings 
taken at each of two or more visits after an initial screening.  
The natural history of essential hypertension :  
• It evolves from occasional to established hypertension. After a long invariable 
asymptomatic period, persistent hypertension develops into complicated 
hypertension, in which target organ damage to the aorta and small arteries, heart, 
kidneys, retina, and central ner vous system is evident. 
• The progression begins with prehypertension in persons aged 10-30 years (by 
increased cardiac output) to early hypertension in persons aged 20-40 years (in which increased peripheral resistance is prominent) to established hypertension in persons aged 30-50 years, and, finally, to complicated hypertension in persons aged 40-60 years.


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Etiologic Classificati on of Hypertension: Hypertension may be classified as either 
essential or secondary.  
I.  Primary or essential hypertension (90-95%):   
o Essential hypertension is diagnosed in individuals in whom generalized or 
functional abnormalities may be the cause of hypertension but no specific 
secondary causes are identified.  
o The pathophyisoliogy of essential hypertension is multifactorial and highly 
complex. A number of factors modulate the blood pressure. These factors include humeral mediators, vascular reactivity, circulating blood volume, 
vascular caliber, blood viscosity, cardiac output, blood vessel elasticity, and 
neural stimulation.


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Internal Medicine 
 
 254Some factors that may contribute for the development of essential hypertension 
include:  
• Genetic predisposition :  the exact mechanism has not been established 
• Environment : a number of environmental factors have been implicated  
o Dietary salt intake and Salt sensitivity   
o Obesity 
o Occupation  
o Family size and crowding  
• Pregnancy-induced hypertension:  Toxemia of pregnancy   
 II. Secondary causes of hypertension:  
In 5-10 % of patients with hypertension, the hypertension is secondary to an identifiable disorder.   
A. Renal Hypertension  (2.5-6%) a variety of renal diseases may be accompanied by 
hypertension  
• Renal parenchymal disease  :  
o Chronic pyelonephritis  
o Acute and chronic glomerulonephritis  
o Polycystic kidney disease  
o Urinary tract obstruction  
o Renin-producing tumor  
• Renovascular hypertension  (0.2-4%) 
o Coarctation of aorta  
o Vasculitis  
o Collagen vascular disease 
B. Endocrine (1-2%)  –  
• Oral contraceptives 
• Adrenocoritical hypertension   
o Primary aldosteronism  
o Cushing syndrome 
o Congenital adrenal hyperplasia 
• Pheochromocytoma  
• Acromegally


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Internal Medicine 
 
 255• Myxoedema  
• Thyrotoxicosis 
C. Neurogenic :  
• Psychogenic  
• Increased intracranial pressure 
• Acute spinal cord section  
D. Drugs and toxins  
• Alcohol  
• Adrenergic medications  
 
Consequences of Hypertension (End organ /target organ damage) 
Patients with hypertension die prematurely, the most common cause of death is heart disease, 
with stroke and renal failure also frequent, particularly in patients with retinopathy 
1. Effects on the Heart : 
• Left ventricular hypertrophy as a compensatory mechanism  
• Coronary artery disease /Ischemic heart disease:  
o Angina Pectoris  
o Myocardial infarction which  may lead to heart failure 
2. Neurologic effects   
a. Retinal changes :  
i. Exudates: hard and soft exudates  
ii. Hemorrhages: dot and bloat hemorrhages 
iii. Thickening of arterioles – copper wiring Æ silver wiring  
iv. Abnormalities on arteriolo –venular crossings ( A/V crossings )  
v. Papilledema 
b. Central nervous system dysfunction  
i. Cerebrovascular disease 
 Transient ischemic attacks : episodic dizziness , unilateral 
blindness , hemiparesis etc 
 Stroke  
• Ischemic stroke : due to atherosclerosis of cerebral blood 
vessels


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Internal Medicine 
 
 256• Hemorrhagic stroke: as a result of elevated arterial 
pressure and formation of vascular micro- aneurysms. 
ii. Hypertensive encephalopathy : consists of severe hypertension, 
altered state of consciousness, increased intracranial pressure with 
papilledema and seizure. Focal neurologic deficits are not common. 
3. Effects on the kidneys  : 
• Arteriolosclerosis of the afferent and efferent arterioles and the glumerular 
capillary tuft impairs renal function. Patients may have proteinuria and microscopic hematuria  and later on develop chronic renal failure.  
 
Risk factors for an adverse pr ognosis in hypertension: 
• Black race  
• Youth  
• Male sex  
• Smoking 
• Diabetes mellitus  
• Hypercholesterolemia 
• Obesity  
• Excess alcohol intake  
• Evidence or of end organ damage  
 
Approach to a patient with Hypertension:  
Diagnosis of hypertension :  is confirmed after an elevated blood pressure ≥ 140/90 mm Hg, 
properly measured, has been documented on at least 3 separate occasions (based on the 
average of 2 or more readings taken at each of 2 or more visits after initial screening). An accurate measurement of blood pressure is the key to diagnosis . 
• Several determinations should be made over a period of several weeks.  
• At any given visit, an average of 3 blood pressure readings taken 2 minutes apart 
using a mercury manometer is preferable.  
• Blood pressure should be measured in both the supine and sitting positions,


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• At any given visit, an average of 3 blood pressure readings taken 2 minutes apart 
using a mercury manometer is preferable.  
• Blood pressure should be measured in both the supine and sitting positions, 
auscultating with the bell of the stethoscope.


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Internal Medicine 
 
 257• On the first visit, blood pressure should be checked in both arms and in one leg to 
avoid missing the diagnosis of coarctation of aorta or subclavian artery stenosis.  
• As the improper cuff size may influence blood pressure measurement, a wider cuff is 
preferable, particularly if the patient's arm circumference exceeds 30 cm.  
• The patient should rest quietly for at least 5 minutes before the measurement.  
• Although somewhat controversial, the common practice is to document phase V (a 
disappearance of all sounds) of Korotkoff sounds as the diastolic pressure. 
Patient evaluation : In evaluating a patient with hypertension the initial history, physical 
examination and laboratory should be directed at  
1) Establishing pretreatment base line hypertension : 
2) Identifying correctable secondary caused of hypertension 
3) Determining if target organ damage is present: patients may have undiagnosed 
hypertension for years without having had their blood pressure checked. Therefore, a search for end organ damage should be made through proper history and 
physical examination. 
4) Determining whether other cardiovascular risk factors are present  
5) Assessing factors that may influence the type of therapy or be changed adversely 
by therapy 
Clinical symptoms and History:   
• Most patients with hypertension have no specific symptoms and are identified only 
in the course of physical examination


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by therapy 
Clinical symptoms and History:   
• Most patients with hypertension have no specific symptoms and are identified only 
in the course of physical examination 
• If patients develop symptoms, the they may be attributable to   
¾ The elevated BP itself or 
¾ The end organ damage associated with hypertension or  
¾ The underlying secondary disease  
Some of the symptoms may be  
• Headache:  though popularly considered symptom of high BP, it is a characteristic 
of only sever hypertension. Such headaches are localized to the occipital region  
and present when the patient awakens in the morning  but subsides spontaneously 
after several hours 
• Dizziness  , palpitation , easy fatigability and impotence  
• Symptoms referable to vascular diseases or evidences of target organ damage include


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Internal Medicine 
 
 258o Epistaxiis , hematuria  
o Retinal changes Æblurring of vision  
o Cerebrovascular damages : Transient ischemic attacks Æ episodes of 
weakness or dizziness or Stroke may occur ( hemorrhagic or ischemic ) 
o Cardiovascular damages : chest pain /angina pectoris or myocardial 
infarction which may cause dyspnea due to  heat failure  
o Pain due to dissecting aorta 
 
Symptoms/history suggesting underlying disease 
• A history of known renal disease, abdominal masses, anemia, and urochrome 
pigmentation.  
• A history of repeated UTI may suggest chronic pylonephritis.   
• A history of sweating, labile hypertension, headache, nervousness, postural 
dizziness, palpitations and weight loss may suggest the diagnosis of pheochromocytoma.  
• A history of polyuria, polydiepsia and muscle weakness may be to secondary to 
hypokalemia associated with aldosteronism.  
• A history of weight gain , emotional labiality may suggest Cushing’s syndrome  
•  A history of cold or heat tolerance, sweating, lack of energy, and bradycardia or 
tachycardia may indicate hypothyroidism or hyperthyroidism. 
• A history of drug ingestion, including oral contraceptives, licorice, and 
sympathomimetics, should be looked for. 
Predisposing factors for hypertension  
• Strong family history of hypertension  
• Age : secondary hypertension often develops before the age of 35 or after 55 
 Associated cardiovascular risk factors: 
• Cigarette smoking


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Predisposing factors for hypertension  
• Strong family history of hypertension  
• Age : secondary hypertension often develops before the age of 35 or after 55 
 Associated cardiovascular risk factors: 
• Cigarette smoking  
• Lipid abnormality or hypercholesterolemia,  
• Diabetes mellitus 
• Family history of early deaths due to cardiovascular diseases  
• Alcoholism.


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Internal Medicine 
 
 259• Obtain a history of over-the-counter medication use, current and previous 
unsuccessful antihypertensive medication trials 
 
Physical Examination:   
• General appearance: 
o Round face and truncal obesity suggests Cushing syndrome  
o Muscular development in the upper extremities out of the proportion of the  
lower extremities suggests coarctation of the aorta 
• Proper measurement of blood pressure 
o Compare the BP and pulses in the two  upper extremities and in supine and 
standing position 
o A rise in diastolic pressure when the patient goes from supine to standing 
position is most compatible with essential hypertension while a fall in BP in the absence of antihypertensive medications suggests secondary hypertension. 
• Funduscopic evaluation of the eyes :  should be performed to detect any 
evidence of hypertensive retinopathy. Some of the findings may be flame-shaped hemorrhages and cotton wool exudates. The presence of papilledema and other neurologic signs raises the possibility of increased intracranial pressure 
• Palpation of all peripheral pulses should be performed . Mainly palpation and 
auscultation of carotid arteries. Femoral pulse should be felt and compared with radial pulse. Radio femoral delay suggests Coarctation of the aorta. 
• A careful cardiac examination:  is performed to evaluate signs of LVH. These 
include displacement of apex, a sustained and enlarged apical impulse, and the presence of an S


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• A careful cardiac examination:  is performed to evaluate signs of LVH. These 
include displacement of apex, a sustained and enlarged apical impulse, and the presence of an S
4. Occasionally, a tambour S 2 is heard with aortic root dilatation. 
• Abdominal examination:  
o Look for renal artery bruit over the upper abdomen; the presence of a 
unilateral bruit with both a systolic and diastolic component suggests renal 
artery stenosis. 
o Palpate for an abdominal aneurysm, enlarged kidneys of polycystic kidney 
diseases.


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Internal Medicine 
 
 260Diagnostic workup 
Laboratory investigations:  
Unless a secondary cause for hypertension is suspected, only the following routine 
laboratory studies should be performed:  
• CBC and Hematochrite 
• Urinalysis including microscopy , protein , blood and , glucose 
• Fasting blood glucose   
• Serum electrolytes : serum K+  
• Lipid profile (total cholesterol, low-density lipoprotein [LDL] and high-density 
lipoprotein [HDL], and triglycerides). 
• Serum creatinine,  uric acid,  
• ECG 
Imaging Studies:  
• Echocardiography : to detect LVH  
Special studies to screen for Secondary hypertension: should be requested only when 
secondary hypertension is strongly suspected. 
• Renovascular disease  : ultrasound and Doppler flow study 
• Pheochromocytoma  : 24 hrs urine assay of metanehprines and catecholamine 
• Cushing’s syndrome : overnight dexamethason suppression test or 24 hrs urine 
cortisol 
• Primary aldosteronism : plasma aldostrone  
• Thyrotoxicosis  or Myxoedema  : Thyroid function test ( TSH , T 3 and T 4 ) 
 
Therapy of Hypertension  
Indication for treatment: 
• Patients with a diastolic pressure >90mm Hg or systolic pressure > 140 mm Hg 
repeatedly 
• Isolated systolic hypertension (systolic BP > 160 with diastolic BP < 89 mmHg) if the 
patient is older than 65 years. 
Goal of therapy :  
• Reducing the diastolic BP to < 90 mmHg and systolic BP < 150mmHg.  
1. General measures : non pharmacologic therapy


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Internal Medicine 
 
 261a. Sodium restriction : intake not more than 100 mmol/d (2.4 g sodium or 6 g 
sodium chloride). 
b. Lifestyle modifications .  
 Weight reduction in obese patients  
 Limitation of  alcohol intake : alcohol potentiates the action of 
catecholamines  and may exacerbate hypertension 
 Regular physical exercise: increase aerobic activity (30-45 min most 
days of the week).  
 Maintain adequate intake of dietary potassium, calcium and 
magnesium for general health. ( healthy diet like fruits, vegetables, 
etc) 
 Stop smoking  
 Reduce intake of dietary saturated fat and cholesterol 
2. Pharmacologic therapy . 
A. Diuretics : are often the first line drugs , and reduce extra cellular fluid volume  
• Thiazide diuretics : are more effective anti-hypertensive agents than loop 
diuretics  Dose:  Hydrochlorothiazide  25 mg PO daily and may be increased 
gradually  
Side effects:  hypokalemia, hyperuric emia, hyperglycemia 
Contraindcation: Gout 
• Potassium-sparing diuretics (e.g. Spironolactone )   : is a competitive 
inhibitor of aldosteron and may be used in primary hyperaldosteronism (as an additional therapy in combination with thiazide diuretics) Dose: 25-50 mg PO 2 to 4 times daily 
B. β-adrenergic blocking agents  :  reduce cardiac output and rennin release  
• β-blockers :  Propanolol  , Metoprolol  , Labetolol , Carvidolol , Atenolol 
  Doses: Propranolol 20 mg PO /day to Maximum of 120 mg PO 4X/day


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B. β-adrenergic blocking agents  :  reduce cardiac output and rennin release  
• β-blockers :  Propanolol  , Metoprolol  , Labetolol , Carvidolol , Atenolol 
  Doses: Propranolol 20 mg PO /day to Maximum of 120 mg PO 4X/day 
               Metoprolol: 25 – 150 mg PO BID 
  Atenolol: 25-100 mg PO/day 
Side effects:  bronchospasm, bradycardia, worsening of heart failure, 
impotence, depression 
Contraindication:  Asthma, peripheral vascular disease (severe)


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Internal Medicine 
 
 262C. Centrally acting agents : These agents inhibit sympathetic out flow from the 
CNS. 
• Methyldopa  : 250 mg -1000 mg PO BID , TID or QID  
Side effects:  postural hypotension, depression, gyneacomastia.  
D. Vasodilators:  dilate arteriols and arteries, reducing peripheral vascular 
resistance which inturn reduces high blood pressure. 
• Hydrallazine  : Oral 10-75 mg PO QID  
                            Paraneteral: 10-50 mg IV or PO every 6 hours. 
Side effects : – headache, lupus erythromatosis like syndrome  
• Minoxidil : 2.5 -40 mg PO BID  
  Side effects : Orthostatic hypotension 
E. Calcium channel blockers : by modulating calcium release in smooth muscles, 
calcium channel blockers reduce smooth muscle tone, resulting vasodilatation. 
Dihydropyridines:  Nifedipine, Felodipine, Amlodipine  
Non dihydropyridines  : Diltiazime, and Verapamil 
Doses:  Nifedipine: 30 – 90 mg PO daily 
Amlodipine: 2.5 -10 mg PO daily 
Side effects  : Dihydropyridines:  headache , tachycardia  , GI disturbance  
Non dihydropyridines  have cardio depressant effect and their use 
may be problematic in CHF patients   
Contraindication: Heart block, heart failure 
F. ACE inhibitors: inhibit the conversion of angiotensin I to angiotensin II (a potent


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Non dihydropyridines  have cardio depressant effect and their use 
may be problematic in CHF patients   
Contraindication: Heart block, heart failure 
F. ACE inhibitors: inhibit the conversion of angiotensin I to angiotensin II (a potent 
vasoconstrictor). By doing so ACE inhibitors reduce peripheral resistance. In addition they reduce aldosteron production, reducing the retention of sodium and water. Captopril , Nezapril , Enalapril , Fosinopril , Ramipril   
Doses : Captopri  : 12.5 -75  mg PO BID  
Enalapril : 2.5-40 mg daily 
Side effects : Cough, Leucopenia, angioedema, hyperkalemia. 
Contraindicated in:  Bilateral renal artery stenosis, Renal failure.  
G. Angiotensin receptor blockers : they block the angiotensin system without 
causing some of the annoying side effects of ACE inhibitors such as cough. Losartan:  25-50 mg once or twice daily 
Side effects : hypotension


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Internal Medicine 
 
 263Stepwise prescription of anti -hypertensive medication: 
• Diuretics are often preferred as first line drugs. They may be effective alone in mild 
hypertension. However most of the time they are used in combination with other 
drugs like: β –blockers, ACE inhibitors or Calcium channel blockers.  The addition of 
12.5 – 25 mg of Hydrochlorothiazide will potentiate the activity of a number of antihypertensive drugs, particularly ACE inhibitors. Such combination has an additive effect, controlling blood pressure in up to 85% of patients 
• The dosage of be anti-hypertnsivedrugs should be escalated till BP is well controlled  
• If one drug fails to control the BP consider changing the antihypertensive drug  
• If the blood pressure is still uncontrolled consider using multiple drugs which act at 
different sites and have additive effect. Most drug combinations, using agents that 
act by different mechanisms, have an additive effect. The combination of a calcium 
channel blocker with either an ACE inhibitor or a dihydropyridine calcium channel blocker and a beta-blocker has additive effects. 
• Some combinations may not be additive, including a beta-blocker and ACE inhibitor, 
a beta-blocker and an alpha1-blocker and an alpha2 stimulant. 
• Some combinations may have additive adverse effects; these include a beta-
blocker combined with Verapamil or Diltiazem, which leads to cardiac depression, bradycardia, or heart block.


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• Some combinations may have additive adverse effects; these include a beta-
blocker combined with Verapamil or Diltiazem, which leads to cardiac depression, bradycardia, or heart block.  
• If the BP is still resistant to treatment add direct vasodilators.


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Internal Medicine 
 
 264Choice of anti hypertensive drugs in certain situations for which a specific class of drug 
may be administered. 
• Thiazides (e.g.Hydrochlorothiazide) :is the preferred therapy for uncomplicated 
hypertension ,  systolic hypertension in elderly people and  older diabetic patients without nephropathy 
• ACE inhibitor:  should be the initial treatment in situations in which hypertension is 
associated with congestive heart failure, diabetes mellitus with proteinuria, and post myocardial infarction with systolic left ventricular dysfunction. In patients who develop persistent cough while on ACE inhibitor therapy, an angiotensin II receptor 
antagonist may be substituted, but these agents' efficacy in lowering cardiovascular 
mortality rates has not yet been proven.  
• Β-blockers :  are often preferred in post–myocardial infarctionand useful also for 
uncomplicated hypertension.  
• A diuretic or a long-acting calcium channel blocker  may be more effective in 
elderly patients with isolat ed systolic hypertension.  
• Calcium channel blockers:  Nifedipine is preferred therapy for systolic hypertension 
and an alternative therapy in uncomplicated hypertension.  
• Central acting agents  (e.g. Methyldopa) may be used as alternative therapy for 
uncomplicated hypertension. 
 
Hypertensive crisis :  is defined as severe hypertension characterized by diastolic blood


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• Central acting agents  (e.g. Methyldopa) may be used as alternative therapy for 
uncomplicated hypertension. 
 
Hypertensive crisis :  is defined as severe hypertension characterized by diastolic blood 
pressure greater than 130 mmHg. Blood pressure elevation to such degree can cause vascular damage, encephalopathy, retinal hemorrhage, renal damage and death. 1 –2% of the hypertensive population develop this complication.  It is categorized into two:  
• Hypertensive Emergency  in which there is acute impairment of an organ system (CNS, 
CVS, Renal). In these conditions, the blood pressure should be lowered aggressively over minutes to hours.  
• Hypertensive Urgency  in which BP is high and there is potential risk but not yet caused 
acute end-organ damage. These patients require BP control over several days to weeks.  
Diagnosis : A diastolic pressure of 130 mmHg, funduscopic finding of papilledema, change 
in neurologic and mental status and abnorma l renal sediments are the hallmarks of 
hypertensive crisis


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Internal Medicine 
 
 265Approach to patients with hypertensive crisis : 
• Rapid assessment of the patient with brief history and targeted physical 
examination (of the CNS, CVS , retina ),  
• Laboratory investigations  : 
o CBC 
o Urinalysis  
o Renal function test 
o ECG 
Treatment “treats the patient, not the number” 
General measures : 
Initial considerations: look if the patient is in a stressful situation .Place the patient in a quiet room and reevaluate after initial interview, some patient’s BP lowers below a critical level after relaxation.  
Pharmacologic treatment:  
• If the patient has Hypertensive emergency, lower the BP rapidly by 25% of the 
diastolic BP and not less than 95mmHg.  
• Use rapidly acting antihypertensive (IV hydrallazine, Soduim Niteroprusside or 
Sublingual Nifedipine). 
o Soduim Niteroprusside : is an effective treatment.  
 Dose : 0.5-8 microgram/kg/min through continuous IV infusion till BP 
is lowered to the desired level 
o Hydralazine  10 -20 mg IV stat to be repeated every 20 -30 minutes can also 
be used 
o Labetalol : 2mg /min through continuous IV infusion 
• As the patient’s BP stabilizes start long term oral anti hypertensive agents. 
• Those patient with urgency, could be discharge with close follow –up and oral 
medication.  
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Hypertensive vascular diseases, pages 1463-1480


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• Those patient with urgency, could be discharge with close follow –up and oral 
medication.  
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Hypertensive vascular diseases, pages 1463-1480 
2. Myers R. Allen , National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Hypertension, 346-364.


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Internal Medicine 
 
 2668. Pericarditis and Pericardial effusion                        
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Pericarditis.  
2. List the etiologies of Pericarditis.  3. Describe the different types of Pericarditis. 
4. Understand the pathophysiology of Pericarditis. 
5. Identify the clinical manifestation of Pericarditis. 
6. Identity acute and chronic complications of Pericarditis.  
7. Understand the diagnostic approach of Pericarditis. 
8. Understand the principle of management of Pericarditis.  
 
Definition: Pericarditis is an inflammation of the pericardium surrounding the heart. 
Percarditis and   cardiac tamponade are clinical problems involving the potential space surrounding the heart or pericardium. Pericarditis is one cause of fluid accumulation in this 
potential space and cardiac tamponade is the hemodynamic result of fluid accumulation.  
 
Pathophysiology: The pericardium consists of an outer fibrous layer (parietal pericardium) 
and an inner serous layer (visceral pericardium).  Normally the two layers are separated by 
a small quantity of fluid (15-50 ml).The pericardium  serves as a protective barrier from the


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and an inner serous layer (visceral pericardium).  Normally the two layers are separated by 
a small quantity of fluid (15-50 ml).The pericardium  serves as a protective barrier from the 
spread of infection or inflammation from adjacent structures. It also prevents sudden dilatation of the cardiac chambers during exercise and hypervolumia. It restricts the anatomic position of the heart and minimizes friction with the surrounding structures. Approximately 120 cc of additional fluid can accumulate in the pericardium without an 
increase in pressure. Further fluid accumulation can result in marked increases in 
pericardial pressure, eliciting decreased cardiac output and hypotension (cardiac tamponade). The rapidity of fluid accumulation influences the hemodynamic effect.


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Internal Medicine 
 
 267Table –III-8-1.  Classification of Pericarditis  
 
 
Clinical classification   Etiologic Classification  
I.  Acute pericarditis (<6 weeks) 
a. Fibrinous 
b. Effusive (serous or sanguineous) 
II.  Subacute pericarditis (6 weeks to 6 
months) 
a. Effusive-constrictive b. Constrictive 
III. Chronic pericarditis (over 6 
months) 
a. Constrictive b. Effusive c. Adhesive (nonconstrictive) 
  I. Infectious Pericarditis 
a. Viral b. Pyogenic 
c. Tuberculous 
d. Fungal   
II. Noninfectious Pericarditis  
a. Uremia b. Acute myocardial infraction 
c. Neoplasm 
d. Idiopathic   
III. Hypersensitivity/autoimmune 
a. Rheumatic fever 
b. Rheumatoid arthritis 
c. SLE  d. Posttraumatic    
TB pericarditis is quite common in HIV positive patients.  
 
Clinical features  
Pericarditis 
• The most common symptom of acute pericarditi s is precordial or retrosternal chest 
pain, usually described as sharp or stabbing. 
o Pain may be of sudden or gradual onset and may radiate to the back (left 
trapezial ridge), neck, left shoulder, or arm. 
o Movement or inspiration may aggravate the pain. 
o Pain may be most severe when the patient is supine and can be relieved 
when the patient leans forward while sitting. 
• Commonly associated symptoms include low-grade intermittent fever, dyspnea, 
cough, and dysphagia.


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 268• In tuberculosis pericarditis, fever, night sweats, and weight loss are commonly 
noted (80%). 
• Some patients may present with acute abdominal pain. 
Cardiac tamponade 
• Patients may present subacutely with symptoms of anxiety, dyspnea, orthopnea, 
fatigue, or altered mental status. 
• Patients may have a history of medical illnesses associated with pericardial 
involvement, particularly end-stage renal disease (ESRD). 
• Traumatic tamponade may present with acute dyspnea or altered mental status. 
• A waxing and waning clinical picture may be present in intermittently 
decompressing tamponade. 
 
Physical findings:  
Pericarditis 
• The classic sign of acute pericarditis is pericardial friction rub , which is scratchy, 
leathery sound heard during both systole and diastole. It is best, heard at the lower 
left sternal border or apex when the patient is positioned sitting forward. Friction rub 
may be transient from one hour to the next and is present in approximately 50% of 
cases. A friction rub may be distinguished from a cardiac murmur by its changing character from heartbeat to heartbeat and patient position changes. A friction rub is closer to the ear on auscultation than a murmur. 
• Fever: usually is low grade, but it may occasionally reach 39
0 C. 
• Cardiac arrhythmias: Premature atrial and ventricular contractions occasionally are 
present. 
• Tachypnea and dyspnea: Dyspnea is a frequent complaint and it may be severe


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• Fever: usually is low grade, but it may occasionally reach 39
0 C. 
• Cardiac arrhythmias: Premature atrial and ventricular contractions occasionally are 
present. 
• Tachypnea and dyspnea: Dyspnea is a frequent complaint and it may be severe 
with myocarditis, pericarditis, and tamponade. 
• Ewart sign  (dullness and bronchial breathing between the tip of the left scapula and 
the vertebral column) 
• Hepatomegally and ascites may be found. 
Cardiac tamponade  
• As the volume of pericardial fluid increases, the capacity of the atria and ventricles 
to fill is mechanically compromised, leading to reduced stroke volume and tamponade. It is influenced by volume and rate of accumulation.


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Internal Medicine 
 
 269• Beck triad  (jugular venous distention, hypotension, and muffled heart sounds) 
• Neck vein distension is a common finding: but Kussmaul’s sign is absent  
• Hypotension to the extent of shock: may occur when the cardiac stroke volume 
is significantly reduced and tissue perfusion is compromised   
• Pulsus paradoxus : abnormal fall in blood pressure by more than 10 mm Hg during 
inspiration.  
• Narrow pulse pressure : indicates reduced left ventricular stroke volume. 
• Cyanosis 
• Varying degrees of  altered consciousness 
Diagnostic workup 
Laboratory studies:  
• CBC with differential 
• Elevated erythrocyte sedimentation rate (ESR) 
• HIV testing 
• Antinuclear antibody, rheumatoid factor 
Imaging Studies:  
• Chest radiography: A bottle–shaped heart can be seen with excessive pericardial 
fluid accumulation. In cardiac tamponade (or large effusions), the chest x-ray may 
demonstrate an enlarged cardiac silhouette after 200-250 ml of fluid accumulation. This occurs in patients with slow fluid accumulation, compared to a normal cardiac silhouette seen in patients with rapid accumulation and tamponade. Thus, the 
chronicity of the effusion may be suggested by the presence of a huge cardiac 
silhouette. 
• ECHO:  minimal pericardial effusion in pericar ditis and significant pericardial effusion 
in Chonic pericarditis or Cardiac tamponade.   
• ECG :  
o Acute pericarditis: diffuse ST segment elevation without reciprocal ST segment


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silhouette. 
• ECHO:  minimal pericardial effusion in pericar ditis and significant pericardial effusion 
in Chonic pericarditis or Cardiac tamponade.   
• ECG :  
o Acute pericarditis: diffuse ST segment elevation without reciprocal ST segment 
depression and depression of PR segment is unique to acute pericarditis 
reported in up to 80% of viral pericarditis cases..  
o Cardiac tamponade or massive effusion : electrical alternans is pathognomonic 
of cardiac tamponade and is characterized by alternating levels of ECG voltage 
of the P wave, QRS complex, and T waves. This is a result of the heart 
swinging in a large effusion. Low voltage of ECG.


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 270Treatment  
1. Acute Pericarditis : 
Treating pain and inflammation: 
• Nonsteroidal anti-inflammatory drugs (NSAID): ASA, Indomethacine and Ibuprofen 
are effective in reducing the inflammation and reliving the chest pain. 
• Steroid therapy: intractable cases of pericarditis that fail to respond to NSAID. 
Specific therapy : should be directed towards the cause of pericarditis. 
E.g. Patients with TB pericarditis should be treated with ant TB along with steroid 
2. Cardiac tamponade 
• Patients with evidence of cardiac tamponade need emergency pericadiocentesis i.e. 
removal of fluid from pericardial sac.  
Complications of Pericarditis:  
• Recurrence : pericarditis may recur in 15-32% of patients  
• Cardiac tamponade  
• Chronic constrictive pericarditis 
• Cardiac perforation at time of pericardiocentesis 
• Bronchopericardial fistula: This was noted as a complication of multi–drug-resistant 
TB in a patient with HIV. 
Prognosis: The prognosis of pericarditis depends upon the etiology of the pericardial 
infection or inflammation as well as the presence of a pericardial effusion and/or 
tamponade.    
 References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Pericardial disease, pages 1414-1419.


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 2719. Ischemic Heart Diseases 
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Ischemic Heart Diseases. 
2. List the etiologies of Ischemic Heart Diseases. 3. Describe the different types of Ischemic Heart Diseases. 
4. Understand the epidemiology of Ischemic Heart Diseases. 
5. Understand the pathophysiology of Ischemic Heart Diseases. 6. Identify the clinical manifestation of Ischemic Heart Diseases. 7. Identity consequences of Ischemic Heart Diseases hypertension.  8. Outline the diagnostic approach of Ischemic Heart Diseases. 
9. Understand the principles of management of Ischemic Heart Diseases.  
10. Refer patients with Ischemic Heart Diseases to better facility. 
 
Background  Ischemic Heart Diseases manifests due to an imbalance in myocardial oxygen supply and 
demand, that results in myocardial hypoxemia. The most common cause of myocardischemia is atherosclerotic disease of the coronary arteries. 
Epidemiology   
• IHD is the leading cause of morbidity and mortality in developed countries and it 
incurs greater economic cost. 
• The prevalence of IHD is also on the rise in developing countries as there is a 
change in the life style associated with urbanization including sedentary life style, 
smoking, obesity high fat and energy diet and the associated increased prevalence in Diabetes mellitus. 
• Larger increases in prevalence of  IHD through out the world are projected, and the


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smoking, obesity high fat and energy diet and the associated increased prevalence in Diabetes mellitus. 
• Larger increases in prevalence of  IHD through out the world are projected, and the 
it is likely to become the most common cause of death worldwide by 2020 
 
Etiology/Pathophysiology 
Myocardial ischemia reflects an imbal ance between myocardial oxygen supply and 
demand. Myocardial oxygen demand is mainly determined by heart rate, the force of 
ventricular contraction, and ventricular wall te nsion, which is proportional to the ventricular


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 272volume and pressure. Unless there is a proportionate rise in oxygen supply, conditions that 
increase oxygen demand such as physical exertion result in ischemia Atherosclerosis of coronary artery (CAD) is the most common cause IHD.  
 Risk factors for Coronary artery disease / Ischemic heart diseases 
• Age: the risk of CAD increases progressively with age. The risk of death from CAD 
is 1.5 in 1000 individuals at age 50. 
• Gender  : IHD is more prevalent in men than in women >The difference is more 
marked in premenopausal women compared to men of similar age 
• Lipid abnormalities  :  increased serum LDL level and reduced HDL level with 
hypertrigyceridemia favors the deposition of lipds and choletrol in atherosclerotic plaques 
• Smoking  : cigarette smokers are 60% more likely to develop CAD than non 
smokers 
• Hypertension : increases the risk of CAD both in men and women. 
• Diabetes mellitus  : is associated with significant increase in the risk of CAD  
• Family history : a familial predisposition to CAD exists 
• Oral contraceptive pills : use of OCP is associated with increased risk of CAD. 
• Other risk factors : Gout, Obesity.  
 Atherosclerosis is focal narrowing of arteries which results from a plaque formation. In 
CAD, atherosclerosis risk factors such as hyperlipidemia, cigarette smoking, diabetes 
mellitus, and hypertension apparently disrupt the normal functioning of the vascular endothelium.  Plaques are formed as a result of


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CAD, atherosclerosis risk factors such as hyperlipidemia, cigarette smoking, diabetes 
mellitus, and hypertension apparently disrupt the normal functioning of the vascular endothelium.  Plaques are formed as a result of  
• Intimal smooth muscle proliferation probably as a result of endothelial damage  
• Lipids ( Cholesterol esters ) are deposited at the center of plaques and also with in 
smooth muscle cells 
• A fibrous cup made of connective tissue covers the plaque 
 
As the stenotic lesions grow, perfusion pressure distal to the lesions decreases; in response, coronary arterioles dilate to maintain adequate blood flow preventing ischemic symptoms at rest. During exertion the myocardial oxygen demand increases which couldn’t be matched by


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 273the perfusion via the narrowed coronary artery. The resulting myocardial ischemia results in 
chest pain, called angina pectoris, which is relived by taking rest.  Sometimes atherosclerotic plaques may rapture and a fibrin thrombus is formed overe the 
plaque which completely blocks the narrowed coronary artery and result in myocardial 
infarction. 
 Factors in CAD   
Clinical features of Coronary artery diseases. 
1. 
Angina pectoris : is a chest pain or pressure produced by myocardial ischemia.  
• Anginal pain is often precipitated by exertion. Other factors that increase myocardial 
oxygen demand (e.g. emotional stress, eating meal, sexual intercourse) may also precipitate angina. 
• The chest pain in angina is squeezing in type or a feeling of pressure or tightness in 
the chest. Sometimes it can be burning in nature or felt as epigatric discomfort. 
• Radiation: the pain radiates to the left shoulder, left jaw, teeth or to the left arm. 
Sometimes it may radiate to the right arm. 
• The pain in angina is often reproducible with the same degree of physical exertion. 
The symptom usually begins with low intensity, increase over 2-3 minutes and often lasts less than 15 minutes. Episodes lasting morethan30 minutes suggest myocardial infarction may have occurred 
Types of Angina  
A. Chromic stable angina : angina which recurs under similar circumstances and with 
similar frequency over time.


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Types of Angina  
A. Chromic stable angina : angina which recurs under similar circumstances and with 
similar frequency over time. 
B. Silent ischemia : for every episode of symptomatic ischemia that the patient suffers, 
there are usually four to five episodes of silent (asymptomatic) ischemia. This 
episode can be detected by ECG including stress ECG. Such episodes are less severe in nature and shorter in duration. 
C. Unstable angina : is a term applied to angina when a change in status occurs. 
Unstable angina is progressive and it may be ominous feature of imminent myocardial infarction. So physicians and patients should be aware that close 
observation and intensive therapy are required. It represents a more serious 
situation tan chronic stable angina.  
i. New onset angina   is an angina that progresses in  severity  , duration or 
frequency  over 1-or 2 months


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 274ii. Resting angina : is particularly worrisome because it implies decreased 
supply, rather that increased demand, is causing angina. This suggests 
possible occlusion is imminent. 
 
C. Varian ( Prinzmetal’s ) angina  :  
• This is a type of angina resulting from transient coronary spasm, which 
usually but not always associated with fixed atherosclerotic lesion. The 
spasm produces total but transient coronary occlusion. 
• It usually occurs at rest (often at night) and episodes are frequently 
complicated with ventricular arrhythmias. 
History   
• In a patient presenting with a history of recurrent chest pain, obtain a detailed 
symptom history, including onset, quality, location, duration, radiation, and precipitating and relieving factors.  
• Determine the presence or absence of each of the three following symptom 
complex characteristics:  
1. Substernal discomfort with a characteristic quality and duration 2. Symptoms provoked by exertion or emotional stress, and  3. Symptoms relieved by rest or nitroglycerin.  
• Based on the number of symptom complex present, angina can be  classified as : 
o Typical (definite)  angina if all three of the characteristics  are present 
o Atypical angina (probable)  if two of the characteristics  are present or  
o Non-cardiac chest pain  if none or one of the characteristics is present.  
• If the patient's symptoms are consistent with typical angina, sub-classify the angina


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o Atypical angina (probable)  if two of the characteristics  are present or  
o Non-cardiac chest pain  if none or one of the characteristics is present.  
• If the patient's symptoms are consistent with typical angina, sub-classify the angina 
as stable (unchanged for 2 or more months) or unstable (rest, new-onset, or 
increasing) angina.  
• In patients with typical (definite) or atypical (probable) angina, ask about functional 
limitations  
• Ask about any episodes of dyspnea, palpitations, or dizziness with or without chest 
pain. If the patient has experienced any such episodes, ask about the same symptom variables that are applicable to typical angina  
• Assess potential risk factors for CAD, includ ing those related to lifestyle, habits, past 
medical history, family history, and hormone therapy


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 275• Ask about a history of symptoms, such as exertional dyspnea, orthopnea, and 
bilateral leg swelling, that suggest left ventricular (LV) dysfunction or heart failure 
and nocturia   
• Ask about other potential causes of chest pain, especially if the symptoms have 
changed, new symptoms have arisen, or the patient is at low risk for CAD.  
Physical Examination  
• In a patient presenting with suspected stable angina, perform a complete physical 
examination to help identify the cause of the chest pain and any comorbid disorder(s)  
• Assess the vital signs, especially for hypertension, tachycardia, bradycardia, 
arrhythmia, and tachypnea  
• Closely examine the head and neck, especially for signs of anemia (mucous 
membrane pallor), thyroid disease (exophthalmos, thyromegaly), 
hypercholesterolemia (Xanthelema which is the deposit of lipids in the skin of the 
eyelids) or atherosclerosis (carotid bruit)   
• Perform a general and peripheral vascular examination to identify signs of 
generalized or peripheral atherosclerosis (e.g., inequality of blood pressure in arms, diminished pedal pulse, and abdominal aneurysm).  
• Carefully examine the heart for evidence of hypertrophy, murmurs, and third or 
fourth heart sounds (S3, S4).  
• Examine the lungs for rales (crackles) and other abnormal breath sounds.  
• Examine the lower extremities for dependent (ankle) edema, tendinous xanthomas


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fourth heart sounds (S3, S4).  
• Examine the lungs for rales (crackles) and other abnormal breath sounds.  
• Examine the lower extremities for dependent (ankle) edema, tendinous xanthomas 
(lipid deposit), weak pulses, or cutaneous signs of ischemia or necrosis.  
 
 Diagnostic workup:  
Electrocardiography: 
Resting ECG : 
• ECG taken when the patient is not in pain may be normal. The presence of new 
horizontal or down sloping of ST segment depression and new T-wave inversion are 
suggestive of myocardial ischemia. 
• ST segment elevation associated with pain which returns to normal as the pain 
wanes suggest variant angina


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 276Stress ECG :  
• Recording ECG during exercise increases the sensitivity and specificity of ECG. 
This helps to quantify the patient’s exercise tolerance. The presence of new 
horizontal or down sloping of ST segment depression has sensitivity of 70 % and specificity of 90 %. 
Radiologic/Imaging   
• Chest-ray in patients with symptoms and signs of congestive heart failure  
• Stress radionuclide ventricuography 
• Stress echocardiography 
• Cardiac catheterization  
 
Other laboratory tests  
• Hemoglobin or CBC, fasting blood glucose,  
• Serum lipid profile  
Differential Diagnosis  
Consider other cause of chest pain like  
• Pleurisy  
• Pneumonia 
• Pericarditis 
• Ischemia associated with aortic stenosis, or hypertrophic cardiomyopathy  
 
Treatment for Angina  
Therapy for angina should be directed either towards reducing myocardial oxygen demand, 
or to compensate for impaired flow through diseased coronary arteries or at increasing 
myocardial oxygen supply (i.e. blood flow) 
General measures  
Lifestyle Measures  
• Counsel patients about cessation of smoking 
• Diet (‘healthy’ diet like low fat  and low caloric diet with increased habit of eating 
fruits and vegetables) 
• Regular exercise 
• Weight reduction.


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 277Medical therapy 
a) Nitrates : this class of drugs produce venodilation and to lesser extent arteriolar 
dilation. These effects reduce blood pressure and reduce cardiac size. 
Instruct patients about how and when to use short-acting nitrates (e.g., 0.4 mg 
sublingual nitroglycerin) for acute attacks, unless nitrates are contraindicated 
Consider long-acting nitrates in patients who have refractory chest pain despite 
maximal tolerated beta-blocker therapy, or in patients who would benefit from after load reduction  
To avoid nitrate tolerance in patients requiring long-acting nitrates, prescribe a 10- 
to 12-hour nitrate-free period daily.  Nitroglycerine 0.3-0.6 mg  sublingual as soon as the pain starts or 5 minutes 
before a stressful activity. Isosorbide dinitrate slow release : 10-60 mg PO TID or 2.5 -10 mg sublingual 
every 4-6 hrs 
b) β-blockers : reduce heart rate and myocardial contractility. By doing so reduce 
cardiac oxygen demand. Propranolol, Atenolol, Nadolol, and Timolol may be used. 
Propranolol:  20 -80 mg PO BID to QID 
Metoprolol:  25-200 mg Po BID  
Atenolol:  50 -150 mg PO daily 
N.B. Consider the patient's concomitant health problems, when selecting a specific beta-blocker Contraindicated  in patients with asthma and severe form of CHF 
 
c) Calcium channel blockers : decrease the tone of the smooth muscle of coronary 
arteries.  These drugs are especially effective in preventing coronary spasm that cause 
variant angina.


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c) Calcium channel blockers : decrease the tone of the smooth muscle of coronary 
arteries.  These drugs are especially effective in preventing coronary spasm that cause 
variant angina. 
Nifedipine XL : 30 mg PO O daily 
Verapamil: 180-240 mg daily 
Amlodipine:  5-10 mg daily 
• Consider calcium channel blockers when beta-blockers are contraindicated or 
are not tolerated.


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 278• Consider using combination therapy cautiously (e.g., a beta-blocker and 
calcium antagonist or nitrate) for patients who fail to respond adequately to 
monotherapy.  
d) Anti-platelet agents :  
Aspirin:  small dose of aspirin is recommended for patients with angina to prevent 
the occurrence of myocardial infarction. 
Dose: 75 – 150 mg PO daily. 
e) Lipid lowering drugs  :Generally, prescribe a lipid-lowering medication (statins) and 
a low-fat, low-cholesterol diet for patients with CAD and elevated low-density 
lipoprotein (LDL) levels to achieve an LDL level of less than 100 mg/dl  
f) ACE inhibitor  : may be beneficial in all patients with significant CAD by 
angiography or in those with previous MI who also have diabetes and/or LV systolic 
dysfunction  
g) Treat comorbidities that can provoke or exacerbate angina (e.g., hypertension, 
diabetes mellitus, hyperthyroidism, pulmonary disorders, anemia)  
• N.B Acute Care/Hospitalization : Always refer patients presenting with new-onset, rest, 
or increasing angina to an emergency department, and hospitalize a patient with clinical 
evidence of unstable angina or myocardial infarction.  
Surgical interventions:  
• Percutanous transluminal coronary angioplasty 
• Artherectomey 
• Coronary artery bypass surgery 
Complications  
• In patients with chronic stable angina, be sensitive particularly to accelerating 
symptoms, indicating development of unstable angina. 
Prognosis


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• Artherectomey 
• Coronary artery bypass surgery 
Complications  
• In patients with chronic stable angina, be sensitive particularly to accelerating 
symptoms, indicating development of unstable angina. 
Prognosis  
The main prognostic indicators in patients with ischemic heart disease (IHD) are: 
• The status of left ventricular (LV) function 
• The location and severity of coronary artery narrowing 
• The severity or activity of myocardial ischemia 
• The presence of complex arrhythmias


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 279Acute Myocardial Infarction    (AMI)  
AMI develops when the myocardium is deprived of its blood supply (Oxygen) for a significant 
amount of time. 
AMI may be classified in to  
• Transmural myocardial infarction  : results from obstruction of coronary arteries  
by thrombus or coronary spasm 
• Non Transmural ( subendocardial ) myocardial infarction the cause of which 
remains uncertain 
Symptoms: 
• Chest pain : Sever squeezing or crushing type of chest pain that lasts for more than 
30 minutes and not relived by rest or sublingual nitroglycerine. The pain radiates in 
a similar pattern to angina. The pain usually occurs when the patient is a rest or involved in minimal activity. Emotional  stress may also precipitate AMI. 
 
• Other associated symptoms ; Nausea, vomiting, diaphoresis and shortness of 
breath, anxiety and sense of impending doom. 
Physical examination 
• The patient is in pain and quite apprehensive often appears ashen 
• Hypotension and tachycardia may be present if the infarction is extensive  
• There also may be signs of CHF (E.g.  elevation of JVP , pulmonary rales , and S
3 
gallop ) 
• A new murmur of mitral regurgitation may be present. 
Complications of AMI 
Arrhythmias:  
• Lethal ventricular arrhythmias are the commonest cause of death in the first hour. 
This may include ventricular tachycardias and ventricular fibrillation 
• Atrial arrhythmias ; atrial fibrillation and atrial flutter


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Arrhythmias:  
• Lethal ventricular arrhythmias are the commonest cause of death in the first hour. 
This may include ventricular tachycardias and ventricular fibrillation 
• Atrial arrhythmias ; atrial fibrillation and atrial flutter 
Acute conduction system abnormality   
• The conduction system may be part of the myocardium affected during infarction. 
This may lead to bradycardia and heart block 
• Inferior wall MI occurs when the right coronary artery is occluded. Since it supplies 
the AV node, Sinus bradycardia and varying degree of AV block occur during inferior myocardial infarction.


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 280• Anterior myocardial infarction may lead to Right or left bundle branch blocks 
Pump failure  
• Congestive heart failure is most likely to occur, when 30 % of the myocardium is 
infracted ,  
• Cardiogenic shock , defined as Systolic BP < 90 mmHg: occurs if more than 40% 
of the myocardium is affected by infarction. 
Mitral regurgitation:  may occur if the papillary muscles are affected by infarction. 
Ventricular septal defect :  
• The left ventricular septum may become infracted either in anterior or inferior AMI. , 
leading to rapture of the septum. 
Cardiac rapture :  
• Myocardial infarction of the free wall may lead to eventual perforation of the heart. 
This complication, which results overwhelmingly cardiac tamponade, is nearly 
always fatal. 
Left ventricular aneurysm:   
• The infracted myocardium may evaginate and heal with fibrous connective tissue. It 
may be a source for cardiac emboli. 
Pericarditis:  post AMI pericarditis (Dressler’s Syndrome) which is believed to be 
autoimmune in origin. Diagnostic work up 
1. ECG:  is diagnostic in approximately 85% of cases. 
• Transmural MI/Q-wave MI  :  ST segment elevation in those leads reflecting 
the area of myocardial infarction ,As ST segments fall , Q waves appear and T waves become inverted 
• Subendocadial infarction /Non Q wave MI ;  ECG findings are less certain 
and ST segment depression may be the only finding


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the area of myocardial infarction ,As ST segments fall , Q waves appear and T waves become inverted 
• Subendocadial infarction /Non Q wave MI ;  ECG findings are less certain 
and ST segment depression may be the only finding 
2. Cardiac enzymes  : as myocardial necrosis occurs , the myocardium releases 
cardiac enzymes 
• Creatine phospho kinase ( CPK ) elevation appears 6 hours after infarction  
• Aspartate aminotransfarase ( AAST or SGOT ) elevates 12 hrs after 
infarction  
• Lactate dehydrogenase (LDH): starts to elevate 24 hrs after infarction.


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 281• Cardiac specific troponin-T and cardiac specific troponin- I, are also elevated 
and they are very specific to cardiac muscles. (So this is the preferred 
biomedical test in Developed countries.). These proteins are not normally detectable in the blood of healthy individuals , but rise > 20 X in patients with AMI. 
 
3. Cardiac Imaging  
• Echo: Decrease myocardial function ( decrease ejection fraction ) and 
significant wall motion abnormality may be detected  
• Radionuclide imaging techniques 
 
Management of patients with acute myocardial infarction 
Management of AMI is beyond your capacity and immediate referral to hospitals with 
intensive care unit (ICU) facility is mandatory. However, the management of acute MI is 
outlined as follows 
A. Emergency management  :Management of patients should start before they reach 
the hospital emergency room 
1. General measures  
• Reassure and make the patient comfortable  
• Supply O 2  by mask 
• Secure IV line  
• Give Aspirin 160-325 mg tablets –helps to prevent further platelet 
aggregation  
2. Treatment of pain : 
• Nitroglycerin : sublingual up to three doses of 0.4 mg should be 
administered at about 5 minutes interval for up to three doses. 
• Morphine sulphate:  is very effective analgesic for pain associated with AMI 
origin .It is administered in small doses of 2-4 mg IV every 5 minutes  
3. Limitation of infarct size through reperfusion or revascularization.: 
• Thrombolysis/Fibrinolysis


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origin .It is administered in small doses of 2-4 mg IV every 5 minutes  
3. Limitation of infarct size through reperfusion or revascularization.: 
• Thrombolysis/Fibrinolysis 
¾ Thrombolytic agents : such as Streptokinase , t-plaminogen activator, 
urokinase : these drugs are given to  dissolve the occlusive thrombus 
and promote reperfusion of the infarct related artery reduces


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 282mortality from myocardial infarction when administered within 6 hours 
of the onset of chest pain. 
Contraindication : History of Cerebrovascular hemorrhage, marked 
hypertension, bleeding disorder. 
• Direct percutanous transluminal coronary angioplasty:  in best facilities 
in the developed countries this is the preferred method to restore perfusion 
of occluded coronary artery. When perf ormed by experienced physicians the 
short and long term outcomes are much better than what can be archived 
through thrombolysis or fibrinolysis. 
B. Hospital phase management:  patients should be referred and admitted to 
coronary artery units or ICU. 
1. General measures  
• Activity :  absolute bed rest for the first 12 hours , Sitting on their bed in the 
first 24 hours , the patient may ambulate in their rooms by the 2nd or 3rd day 
• Diet :  Because of the risk of emesis and aspiration soon after AMI , patients 
should receive either nothing or only clear liquids by mouth for the first 4-12 hrs. The diet should be low fat low calori and rich in Potassium 
• Bowel motion : constipation is common and straining may precipitate AMI . 
Fibrous diet and Stool softeners like bisacodyl or Dioctyl sodium sulfosuccinate 200 mg /day are recommended. If the patient remains 
constipated laxatives can be prescribed. 
• Sedation:  many patients require sedation during hospitalization to withstand 
the period of enforced inactivity with tranquility.


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constipated laxatives can be prescribed. 
• Sedation:  many patients require sedation during hospitalization to withstand 
the period of enforced inactivity with tranquility. 
o Diazepam15 – 30 mg or Lorazeam 0.5 to 2mg given 3-4 X daily. 
 
2. Pharmacological therapy 
a) Antithombotic agents  and anti platelet agents : 
• Unfractionated heparin : may be given in patients where there is a risk of 
cardiac thrombus formation and subsequent emboli 
• Anti platelet agents : ASA 75-150 mg Po daily to prevent recurrence of AMI 
b) β-Blockers : have short term and long term benefits for patients with AMI. 
• The short term benefit is they relive pain and decrees the risk of malignant 
arrhythmias


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 283• Long term benefits are : improved myocardial performance and facilitate the 
healing process in Post myocardial infarction patients 
Metoprolol: 25-200 mg BID 
Atenolol: 50-150 mg Po daily 
  Contraindication : Severe CHF, AV block 
c) ACE inhibitors  ; reduce the mortality rate and improve long term survival in post 
AMI patients by preventing cardiac remodeling which may have lead to progressive heart failure. Their effect is additive to what is archived with Aspirin and β-blockers. . The maximum benefit is seen in high risk patients  ( elderly 
patients , significant LV dysfunction ) . ACE inhibitors should be prescribed 
within 24 hours and maximum benefit is archived when they are given at higher 
doses that are recommended. In patients with CHF ACE inhibitors are given indefinitely. 
Captopril: Start with smaller dose 12.5 mg PO day to gradually escalate to 75 mg Po BID 
Enalapril: Start with 2.5 mg PO daily and escalate gradually to 40 mg Po 
daily 
Management of Complications  
Malignant arrhythmias ;  
• Cardiac defibrillation 
• Prophylactic lidocaine  
• Other antiarrhythmic agent; bertyluim tosylate and procainamide 
Treatment of serous conduction disturbances; 
• Sinus bradycardia :Atropine  2mg IV  may restore conduction and restore heart rate 
• AV block : Trans cutanous cardiac pace makers  
Heart failure: 
• Diuretics, Salt restriction, ACE inhibitors, vasodilators. Use of digoxin is 
controversial.


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• Sinus bradycardia :Atropine  2mg IV  may restore conduction and restore heart rate 
• AV block : Trans cutanous cardiac pace makers  
Heart failure: 
• Diuretics, Salt restriction, ACE inhibitors, vasodilators. Use of digoxin is 
controversial. 
Cardiogenic shock:  do Echocardiography to assess the ventricular function 
• IV infusion of fluids to maximize left ventricular filling  
• Use of vasopressors: Dubutamine, dopamine) in IV infusion. 
• Intraaortic balloon pumping  
• Percutanous transluminal angioplasty


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 284Prognosis: depends on two factors  
The extent of coronary artery disease in terms of the number of vessels affected 
• Patents with uncorrected main left coronary artery disease have approximately a 20 
% mortality in the first year  
• Single vessel coronary artery has 2 % annual mortality. 
• Double vessel disease: have approximately a 2- 4 % annual mortality. 
• Triple vessel disease: have 5-8 % annual mortality. 
The extent of ventricular damage: left ventricular ejection fraction  
• An ejection fraction of <40 % doubles the yearly mortality rate at each level of extent 
of coronary disease. 
Revascularization:  significantly improves the short term and long term morbidity and, 
mortality when it is done at the right time by an expert hand.  
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Ischemic heart disease, pages 1434-1448. 
2. Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Ischemic heart disease, pages 15-28.


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 28510. Cardiac Arrhythmias 
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define Cardiac arrhythmias  
2. List the etiologies of arrhythmias. 3. Classify the different types of arrhythmias. 
4. Understand the pathophysiology of arrhythmias. 
5. Identify the clinical manifestation of arrhythmias. 6. Identity consequences of arrhythmias.  7. Understand the diagnostic approach arrhythmias.  
8. Understand the principle of management of arrhythmias.   
9. Refer patients with arrhythmias to appropriate centers  
 
Definition : Cardiac arrhythmias are changes in the regular beating of the heart. The heart 
may seem to skip a beat or beat irregularly or beat very fast or very slow. 
The normal heart beat of a person ranges from 60 -100 beats/min. 
• Many arrhythmias occur in people who do not have underlying heart disease. 
• Most of the time, there may not be a recognizable cause of an arrhythmia.  
• Heart disease may cause arrhythmias. Other causes include: stress, caffeine, 
tobacco, alcohol, diet pills,”K hat”, cough and cold medicines. 
• In some people, arrhythmias are associated with heart disease. In these cases, 
heart disease, not the arrhythmia, poses the greatest risk to the patient. 
• In a very small number of people with se rious symptoms, arrhythmias themselves 
are dangerous. These arrhythmias require medical treatment to keep the heartbeat 
regular.


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• In a very small number of people with se rious symptoms, arrhythmias themselves 
are dangerous. These arrhythmias require medical treatment to keep the heartbeat 
regular.  
• Arrhythmias occur commonly in middle-age adults. As people get older, they are 
more likely to experience an arrhythmia. 
• Patients with arrhythmias often complain that they felt their heart beat very fast, 
experienced a fluttering in their chest, or noticed that their heart skipped a beat. Almost everyone has also felt dizzy, faint, or out of breathe or had chest pains at one time or another.


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 286Classification of Arrhythmias 
1. Bradyarrhythmias: are arrhythmias in which the heart beats slower than normal. 
They result from inadequate sinus impulse  production or from blocked impulse 
propagation. They are not usually cause of concern unless the patient develops 
syncope or presyncope.  
• Sinus bradycardia 
• Sinus pause  
• AV block 
2. Tachyarrythmias : are arrhythmias in which the heart beats faster than normal.  
A. Atrial tachyarrhythmias: tachyarrhythmias originating from the atria.  
i) Regular atrial tachycardias : the heart beats faster but the rhythm is regular  
• Sinus tachycardia  
• Paroxysmal atrial tachycardias 
• Atrial flutter with constant conduction  
ii) Irregular atrial tachycardias : the heart beats faster and the rhythm is 
irregular 
• Atrial fibrillation  
• Multifocal atrial tachycardia 
• Atrial flutter with irregular conduction 
B. Ventricular Tachyarrhythmias: tachyarrhythmias originating from the ventricles.  
• Premature ventricular contraction 
• Ventricular tachycardia 
• Ventricular fibrillation  
Bradyarrhythmias 
1. Sinus bradycardia:  
Causes  
• Physical conditioning in professional athletes 
• Hypothyroidism 
• Sinus node dysfunction 
Therapy 
• If  it is physiologic no need for treatment 
• If it is due to sinus dysfunction and severe  ( the HR  is < 35 beats/min) :


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 287o Atropine : 1mg IV  may temporarily increase the sinus rate 
o Cardiac Pacemaker implantation. 
2. Sick sinus syndrome:  The sinus node does not fire its signals properly, so that 
the heart rate slows down. Sometimes the rate changes back and forth between a 
slow (bradycardia) and fast (tachycardia) rate 
3. AV blocks:  all of the impulses generated from the sinus node are not conducted to 
the ventricles 
2nd degree AV block:  Some atrial impulses are blocked and not transmitted to the 
ventricles  
• Mobitz Type I (Wenckebach) block : the PR interval is progressively 
prolonged until a generated P wave is not conducted. 
• Mobitz Type II block:  there is no prolongation of the PR interval before the 
dropped beat. Often conduction is in a ration of 2: 1and it  is prolonged enough to cause symptomatic bradycardia. 
3
rd Degree (Complete) heart block : No atrial impulses are conducted and the atria 
and the ventricles are contracting independently. The heart rate drops significantly to a range of 20- 40 beats/min and patients become symptomatic. 
Therapy: 
• Pharmacologic therapy : reserved only for acute situations to temporarily increase 
the ventricular rate. 
o Atropine 0.5-2 mg IV or Isoproterenol 1-4 microgram/min IV  
• Permanent cardiac pacemakers  : most symptomatic AV blocks need  permanent 
pacing 
Sinus tachycardia : the sinus node sends out electrical signals faster than usual,


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o Atropine 0.5-2 mg IV or Isoproterenol 1-4 microgram/min IV  
• Permanent cardiac pacemakers  : most symptomatic AV blocks need  permanent 
pacing 
Sinus tachycardia : the sinus node sends out electrical signals faster than usual, 
speeding up the heart rate. It represents physiologic or pathologic increase in the sinus rate 
≥100 beats/min. It rarely exceeds > 200 beats/min  
Supraventricular tachycardia (SVT), paroxysmal atrial tachycardia (PAT) . A 
series of early beats in the atria speed up the heart rate (the number of times a heart beats 
per minute). In paroxysmal tachycardia, repeated periods of very fast heartbeats begin and 
end suddenly. These arrhythmias are sudden onset, often occurring in patients with otherwise normal heart, and characterized by a heart rate of 150-250 beats /min


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 288Common causes  
• Exercise , fever  
• Anxiety ,thyrotoxicosis 
• Hyopoxemia ,hypotension 
• Heart Failure 
Diagnosis: ECG : Faster rate with P waves followed by narrow QRS complexes. 
Treatment:  
• If patient is stable  – No need for treatment, identify and treat the underlying cause. 
• If the patient is hemodynamically unstable  – there is a need for treatment.  
• The patient should be kept in a quiet room 
Mechanical treatment  
o Carotid sinus massage  
o Valsalva maneuver 
o Head immersion in cold water 
Medial therapy: 
 β-blockers, Calcium channel blockers ( Verapamil and Diltiazem ) or  
digoxin can be helpful. 
Atrial flutter : Rapidly fired signals cause the muscles in the atria to contract quickly, leading to 
a very fast, steady heartbeat. Is characterized by an atrial rate of 240-400 beat/min and is 
usually conducted to ventricles with block so that the ventricular rate is a fraction of the atrial 
rate. The block is usually regular so the ventricular rate is regular. Sometimes there may be a 
varying block resulting irregular ventricular beat. 
Causes of atrial flutter : often associated with antecedent hear diseases 
• Coronary artery diseases 
• Pericarditis  
• Valvular heart diseases 
• Cardiomyopathy 
ECG:  Classic saw tooth pattern: 2 or 3 P waves are followed by QRS complex. The block is 
often in a ratio of 2:1 with an atrial rate of 240 beats/min and ventricular rate of 120 beat/min


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 289Therapy: 
• Drugs :   
o Digoxin , Esmolol or Verapamil to control ventricular rate and  
o Quinidine or other ant arrhythmic agents to restore sinus rhythm. 
• Direct current cardioversion:  if the patient is hemodynamically unstable  
Atrial Fibrillation: electrical signals in the atria are fired in a very fast and uncontrolled 
manner. Electrical signals arrive in the ventricles in a completely irregular fashion, so the heart 
beat is completely irregular.  
Common cause of atrial fibrillation 
o Stress , fever  
o Excessive alcohol intake  
o Hypotension 
o Pericarditis 
o Coronary artery disease 
o Myocardial infarction 
o Pulmonary embolism 
o Mitral valve diseases : Mitral stenosis , Mitral regurgitation  and Mitral valve 
prolapse 
o Thyrotoxicosis 
o Idiopathic (lone) atrial fibrillation. 
ECG:  irregularly irregular pattern disorganized atrial activity without discrete P wave. 
Therapy  
If the patient is hemodynamically unstable: direct current synchronous cardioversion: 
 
If the patient is hemodynamically stable 
• Identify and treat the underlying cause  
• Control the ventricular rate : β-blockers , Calcium channel blockers ( Verapamil and 
Diltiazim ) , Digoxin 
• Restore sinus rhythm : Quinidine  
• Anticoagulants : if the atrial fibrillation ahs stayed for more than 1 week to prevent 
thromboembolism


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 290Ventricular tachyarrhythmias :  
Premature ventricular contractions (PVC)  : is a type of arrhythmia in which occasional 
cardiac impulses are originating directly from the ventricles by passing the normal conduction 
system. These are among the commonest arrhythmias. 
ECG:  Wide and bizarre QRS appearing in a relatively normal looking ECG 
Therapy:  most isolated PVCs are benign and need no treatment. 
Ventricular tachycardia : arises from the ventricles, it occurs paroxysmal and exceeds 120 
beats/min, with regular rhythm. There is AV dissociation and the ventricular arrhythmia 
proceeds independently of the normal atrial rhythm. During ventricular tachycardia, the 
ventricles do not have enough time to relax, ventricular filling is impaired and the cardiac output 
significantly decreases. When ventricular tachycardia lasts for more than 30 seconds or requires control because of hemodynamic collapse it is called sustained Ventricular tachycardia. 
ECG:  Bizarre and wide QRS complexes coming in succession with no constant relation to 
P waves. 
Therapy: since this is a life threatening situation urgent intervention is needed 
• Anti-arrhythmic drugs : intravenous administration of Beretylium, Lidocaine or 
Procainamide may be useful in returning the patient’s rhythm to normal while preparation is being made for DC cardioversion. 
• DC cardioversion : is urgently required


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Procainamide may be useful in returning the patient’s rhythm to normal while preparation is being made for DC cardioversion. 
• DC cardioversion : is urgently required  
Ventricular Fibrillation:   electrical signals in the ventricles are fired in a very fast and 
uncontrolled manner, causing the heart to quiver rather than beat and pump blood. It is characterized by lack of ordered contraction of the ventricles. Therefore there is no cardiac out 
put. Thus ventricular fibrillation is synonymous with death unless urgent conversion to effective rhythm can be accomplished.  
Therapy:  patients need cardiorespiratory resuscitation  
• Cardiac resuscitation  
• Mechanical ventilation 
• Cardiac compression and intracardiac adrenalin 
• DC cardioversion using high voltage. 
The place of Surgery in the management of Arrhythmias  
♦ When an arrhythmia cannot be controlled by other treatments, there may be a place 
for surgery. After locating the heart tissue that is causing the arrhythmia, the tissue is altered or removed so that it will not produce the arrhythmia.


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 291Prevention 
If the precipitating factor for arrhythmia is identified, one has to avoid what is causing it.  
E.g. If caffeine or alcohol is the cause, the pati ent has to avoid drinking coffee, tea, colas, or 
alcoholic beverages . 
 
References:  
1. Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Disordrs of cardiac rhythm , pages 1333-1357. 
2. Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Cardiac arrhythmias, pages 7-14.


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Internal Medicine 
 
 292CHAPTER FOUR 
DISEASES OF THE KIDNEYS 
 
1. Introduction to Renal Disease 
 
Learning objectives: at the end of this lesson the student will be able to : 
1. List common etiologies of renal diseases. 
2. Describe the calcification of renal diseases. 
3. Identify common clinical manifestation of renal diseases. 
4. Understand the diagnostic approach to renal diseases.   
 
• Patients with renal disease may have a variety of different clinical presentations.  
• Some have symptoms that are directly refe rable to the kidney (gross hematuria, flank 
pain) or to associated extrarenal symptoms (edema, hypertension, signs of uremia).  
• Many patients, however, are asymptomat ic and are noted on routine examination to 
have an elevated plasma creatinine concentration or an abnormal urinalysis.  
• Specific disorders are more likely to be either acute or chronic in duration, thereby 
narrowing the differential diagnosis among pati ents presenting with similar clinical 
findings related to the kidney. 
 
Major causes of renal diseases .  
Renal function is based upon four sequential steps, which are isolated to specific areas of the kidney or surrounding structures: 
 
1. First, blood from the renal arteries is delivered to the glomeruli. 2. The glomeruli form an ultrafiltrate, which subsequently flows into the renal tubules. 
3. The tubules reabsorb and secrete solute and/or water from the ultrafiltrate.


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1. First, blood from the renal arteries is delivered to the glomeruli. 2. The glomeruli form an ultrafiltrate, which subsequently flows into the renal tubules. 
3. The tubules reabsorb and secrete solute and/or water from the ultrafiltrate. 
4. The final tubular fluid, the urine, leaves the kidney, draining sequentially into the renal             pelvis, ureter, and bladder, from which it is excreted through the urethra. 
The causes of renal disease are traditionally classified based on the portion of the renal 
anatomy most affected by the disorder


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Internal Medicine 
 
 2931. Prerenal disease  – Reduced glomerular perfusion is most commonly caused by 
volume depletion and/or relative hypotension.  This may result from: 
• True hypoperfusion due to bleeding, gastrointestinal, urinary, or cutaneous 
losses, or  
• Effective circulatory fluid volume depletion in congestive heart failure, shock, or 
cirrhosis. 
2. Vascular disease  – The vascular diseases affecting the kidney can be divided into 
those that produce acute and chronic disease.  
• The major acute causes are vasculitis, malignant hypertension, scleroderma, 
and thromboembolic disease. 
• The major chronic disorders are benign nephrosclerosis and bilateral renal 
artery stenosis.  
3. Glomerular disease:         
There are numerous idiopathic and secondary disorders that produce glomerular disease. 
Two general patterns (with considerable overlap in some diseases) are seen:  
• The nephritic pattern which is associated with inflammation on histologic 
examination and produces an active urine s ediment with red cells, white cells, 
granular and often cellular casts, and a variable degree of proteinuria;   
• The nephrotic pattern which is not associated with inflammation on histologic 
examination and is primarily manifested c linically by proteinuria, often in the 
nephrotic range. 
4. Tubular and interstitial disease  – As with vascular disease, the tubular and


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examination and is primarily manifested c linically by proteinuria, often in the 
nephrotic range. 
4. Tubular and interstitial disease  – As with vascular disease, the tubular and 
interstitial diseases affecting the kidney can be divided into those that produce acute and chronic disease.  
• The most common acute tubulointerstitial disorders are acute tubular necrosis, 
which typically occurs in hospitalized patients, acute interstitial nephritis, which is often drug-induced, and cast nephropathy in multiple myeloma.  
• The major chronic tubulointerstitial disorders are polycystic kidney disease, 
vesicoureteral reflux, autoimmune disorders (such as sarcoidosis and Sjögren's syndrome), and analgesic abuse. 
5.  Obstructive uropathy  – Obstruction to the flow of urine can occur anywhere from 
the renal pelvis to the urethra. The development of renal insufficiency in patients


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 294without intrinsic renal disease requires bilateral obstruction and is most commonly 
due to prostatic disease. 
 
 Clinical manifestations  – Patients with renal disease may present with a variety of 
clinical manifestations: 
• Signs and symptoms resulting directly from alterations in kidney function, including 
decreased or no urine output, flank pain, edema, or discolored urine. 
• Asymptomatic elevations in the plasma creatinine concentration or abnormalities 
on urinalysis. 
• Symptoms and/or signs of renal failure, including anorexia, vomiting, mental status 
changes (including seizures), edema, and hypertension. 
• The presence of certain symptoms or signs may suggest an underlying diagnosis.  
E.g.  
¾ Unilateral flank pain is most consistent with a renal stone, renal infarction, 
infection, or obstruction,  
¾ The total absence of urine (anuria) is primarily observed with bilateral 
ureteral obstruction or shock. 
• A constellation of symptoms and signs may also favor a particular set of 
disorders. 
E.g. A patient with edema, hypertension, red to brown colored urine due 
to hematuria (with red cell casts), and a rapidly rising plasma creatinine 
concentration almost certainly has glomerulonephritis or vasculitis. 
• Other manifestations, however, are relatively nonspecific and can be observed 
with a wide variety of disorders. 
 Disease duration : An important aspect of the evaluation of the patient with renal


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• Other manifestations, however, are relatively nonspecific and can be observed 
with a wide variety of disorders. 
 Disease duration : An important aspect of the evaluation of the patient with renal 
disease is the determination of disease duration. As noted above, the differential 
diagnosis can frequently be narrowed if the disease duration is known. 
 
• Comparing the current urinalysis or plasma creatinine concentration with previous results: -  A patient with a current plasma creatinine of 4.0 mg/dL (354 
µmol/L) but a plasma level of 1.0 mg/dL (88 µmol/L) one month previously has acute disease while the same patient with a prior plasma creatinine concentration


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 295of 3.0 mg/dL (265 µmol/L) two years ago has a slowly progressive chronic 
disease. 
• When a previous urinalysis or plasma cr eatinine is unavailable, certain clinical 
elements may suggest the duration of disease. These include : 
¾ The recent onset of symptoms or signs, such as fever and discolored urine, 
suggests an acute process. ¾ An increasing plasma creatinine after the initial evaluation is indicative of at 
least an acute component to the disease, while a stable value suggests a chronic disease. In addition, the rate of rise in the plasma creatinine concentration may help distinguish among possible disorders. 
 
Diagnostic work up of pa tients with Renal Diseases. 
1. Assessment of renal function – Once renal disease is discovered, the presence or 
degree of renal dysfunction should be as sessed and the underlying disorder is 
diagnosed.  
• Glomerular filtration rate  – An estimation of the glomerular filtration rate (GFR), 
usually by the plasma creatinine concentration and less often by the creatinine 
clearance, is used clinically to assess the degree of renal impairment and to follow 
the course of the disease. However, since all renal disorders variably affect renal 
function, estimation of the GFR has no diagnostic utility. 
 
2. Urinalysis : The urinalysis is the most important noninvasive test in the diagnostic 
evaluation, since characteristic findings on microscopic examination of the urine


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function, estimation of the GFR has no diagnostic utility. 
 
2. Urinalysis : The urinalysis is the most important noninvasive test in the diagnostic 
evaluation, since characteristic findings on microscopic examination of the urine 
sediment strongly suggest certain diagnoses. E.g. 
¾ The finding of red cell casts is diagnostic of vasculitis or glomerulonephritis, 
and  
¾ The presence of muddy brown granular casts and epithelial cell casts in a 
patient with acute renal failure is highly suggestive of acute tubular necrosis;  
¾ Even a normal urinalysis has diagnostic utility.  
Urine volume : has little diagnostic value.  
• Anuria (Complete absence of urine output): may be due to shock, complete 
bilateral urinary tract obstruction, renal cortical necrosis, and bilateral vascular


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 296occlusion (as with thrombotic thrombocytopenic purpura-hemolytic uremic 
syndrome). 
3. Radiologic/imaging studies . They are principally required to assess urinary tract 
obstruction, kidney stones, renal cyst or mass, disorders with characteristic 
radiographic findings, renal vascular diseases, and vesicoureteral reflux. 
Renal ultrasonography : 
o Showing small kidneys is most consistent with a chronic disease because 
of the progressive loss of renal parenchyma with time. However, the presence of normal-sized kidneys does not exclude chronic disease 
o Obstructive uropathy: hydronephrosis, hydroureter, Stone, and the site of 
obstruction can be seen by U/S. 
Plain film of the abdomen (KUB):   A plain abdominal radiograph can detect renal 
stones and provide a rough approximat ion of kidney size and shape.  
4. Other studies: may be ordered to make specific diagnosis 
1. Intravenous pyelogram  
2. Renal biopsy has limited value. 
 
References:  
1) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd 
edition Medicine, Clinical assessment of renal function, pages 279-280.


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 2972. Acute Nephritic Syndrome   
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define acute nephritic syndrome.  
2. List the etiologies of acute nephritic syndrome.. 3. Describe the clinical features and diagnostic approach to patients with acute 
nephritic syndrome. 
4. Understand the pathogenesis of Poststreptococcal glomerulonephritis. 5. Identify the clinical manifestation of Poststreptococcal glomerulonephritis.. 6. Identity complications of nephritic syndrome..  7. Understand the diagnostic approach to Poststreptococcal  glomerulonephritis..  
8. Understand the principle of management of Poststreptococcal glomerulonephritis.  
 
Definition 
The acute nephritic syndrome is the clinical correlate of acute glomerular inflammation. In its 
most dramatic form, the acute nephritic syndrom e is characterized by sudden onset (i.e., over 
days to weeks) of acute renal failure and oliguria (<400 mL of urine per day) associated with 
hypertension, edema and the presence of active urinary sediments.  
 Clinical features  
• Extracellular fluid volume expansion, edema, and hypertension develop because of 
impaired GFR and enhanced tubular reabsorption of salt and water. Patients may 
present with congestive heart failure and pulmonary edema.  
• And pictures of acute renal failure may also occur (see later sections). 
• Evidence of the underlying cause can be detected (skin lesions, joint swelling, 
fever)


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present with congestive heart failure and pulmonary edema.  
• And pictures of acute renal failure may also occur (see later sections). 
• Evidence of the underlying cause can be detected (skin lesions, joint swelling, 
fever) 
Laboratory tests 
• Urinalysis: as a result of injury to the glomerular capillary wall, urinalysis typically 
reveals red blood cell casts, dysmorphic red blood cells, leukocytes, and subnephrotic proteinuria of <3.5 g per 24 h ("nephritic urinary sediment"). Hematuria 
is often macroscopic. 
• Renal function test :Elevated level of serum creatinine 
• Serology: Immunologic assays suggesting the underlying disease.


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 298Etiology 
Acute nephritic syndrome can result from renal -limited primary glomerulopathy or from 
secondary glomerulopathy complicating systemic  disease. In general, rapid diagnosis and 
prompt treatment are critical to avoid the development of irreversible renal failure.  
 
Immune-complex glomerulonephritis may be: 
1. Idiopathic 
2. Represent a response to a known antigenic stimulus (e.g., post infectious 
glomerulonephritis) 
3. Part of a multisystem immune-complex disorder (e.g., lupus nephritis, Henoch-Schonlein purpura, cryoglobulinemia, bacterial endocarditis). 
 
 
Poststreptococcal glomerulonephritis 
Etiology and Epidemiology 
• This is the prototypical postinfectious glomerulonephritis and a leading cause of 
acute nephritic syndrome.  
• Most cases are sporadic, though the disease can occur as an epidemic. 
Glomerulonephritis develops, on average, 10 days after pharyngitis or 2 weeks after a skin infection (impetigo) with a nephritogenic strain of group A β-hemolytic 
streptococcus .  
• Immunity to these strains is type-specific and long-lasting, and repeated infection 
and nephritis are rare. Epidemic poststreptococcal glomerulonephritis is most commonly encountered in children of 2 to 6 years of age with pharyngitis during the winter months. This entity appears to be decreasing in frequency, possibly due to 
more widespread and prompt use of antibiotics.


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more widespread and prompt use of antibiotics.  
• Poststreptococcal glomerulonephritis in association with cutaneous infections 
usually occurs in a setting of poor personal hygiene or streptococcal superinfection 
of another skin disease. 
 Clinical picture 
• The classic clinical presentation of postst reptococcal glomerulonephritis is full-blown 
nephritic syndrome with oliguric acute r enal failure; however, most patients have 
milder disease.


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 299• Indeed, subclinical cases outnumber overt cases by four- to tenfold during 
epidemics. Patients with overt disease present with gross hematuria (red or "smoky" 
urine), headache, and generalized symptoms such as anorexia, nausea, vomiting, and malaise.  
• Swelling of the renal capsule can cause flank or back pain. 
Physical examination : Hypervolemia, edema, and hypertension.  
Complications; 
• Congestive heart failure and Pulmonary edema 
• Acute renal failure  
• Sever hypertension with hypertensive encephalopathy. 
Laboratory findings: 
• Urinalysis: the urinary sediment is nephritic, with dysmorphic red blood cells, red 
cell casts, leukocytes, occasionally leukocyte casts, and subnephrotic proteinuria. Fewer than 5% of patients develop nephrotic-range proteinuria.  
• Renal function test : the serum creatinine is often mildly elevated at presentation. 
• Serology:  most patients (>90%) have circulating antibodies against streptococcal 
exoenzymes such as ASO, DNAase.  
Diagnosis: 
Acute poststreptococcal glomerulonephritis is usually diagnosed on clinical and serologic grounds. The characteristic lesion is diffuse proliferative glomerulonephritis.  
Course and prognosis of the disease 
• Poststreptococcal glomerulonephritis is  typically an acute disease, with 
spontaneous recovery occurring in almost all patients, even those who develop renal insufficiency during the acute episode.


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Course and prognosis of the disease 
• Poststreptococcal glomerulonephritis is  typically an acute disease, with 
spontaneous recovery occurring in almost all patients, even those who develop renal insufficiency during the acute episode.  
• Resolution of the clinical manifestations of poststreptococcal glomerulonephritis is 
generally quite rapid, assuming concurrent resolution of the infection .  
• Diuresis typically begins within one week and the plasma creatinine concentration 
returns to the previous baseline by three to four weeks.  
• Hematuria usually resolves within three to six months.  
• The degree of proteinuria also falls during recovery, but at a much slower rate.  
• Generally the long-term prognosis is good.


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 300Treatment  
1. Eliminating the streptococcal infection with antibiotics. 
2. Supportive therapy until spontaneous resolution of glomerular inflammation occurs. 
a. Bed rest  b. Salt restriction  c. Diuretics and are employed to control extracellular fluid volume.  
d. Antihypertensive drugs  to control high blood pressure  
3. Dialysis : some patients may need dialysis


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Internal Medicine 
 
 3013. Nephrotic syndrome: 
 
Learning objectives: at the end of this lesson the student will be able to : 
1. Define nephrotic syndrome.  
2. List the etiologies of nephrotic syndrome. 3. Describe the clinical features of   nephrotic syndrome. 
4. Identity complications of nephrotic syndrome..  
5. Understand the diagnostic approach of nephrotic syndrome.  
6.  Understand the principle of management of nephrotic syndrome.  
 Definition The nephrotic syndrome is a clinical complex characterized by: 
• Significant proteinuria of >3.5 g/1.73m
2/per 24 h (for practical purpose >3.0 to 3.5 g 
per 24 h) is the most important clinical feature  
• Hypoalbuminemia 
• Edema 
• Hyperlipidemia and  lipiduria  and  
• Hypercoagulability  
 
Etiology 
1. Multisystem diseases account for 50 –70 % of adult nephrotic syndrome.  
a. Diabetes mellitus 
b. Collagen vascular diseases  
c. Amyloidosis  
2.  Neoplasms: - leukemias, lymphomas and solid tumors 
3.  Infections: - viral, bacterial, protozoan and helimenthic 
4.   Primary glomerulopathies( Idiopathic ): - account for 30 –50 % of adult nephrotic syndrome 
 Clinical picture 
 
1. Proteinuria and hypoalbuminemia : - In general, the greater the proteinuria, the lower the 
serum albumin level. Hypoalbuminemia is co mpounded further by increased renal catabolism


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 302and inadequate hepatic synthesis of albumin. The proteinuria is believed to be due to increased 
permeability of the glomerular basement membrane to proteins. 2. Edema : - Common sites for edema formation in the early stage include: dependent areas, 
face, peri-orbital areas and scrotum. Hypoalbuminemia and primary water and salt retention by kidneys are the postulated mechanisms for edema formation.  3. Hyperlipidemia : - is believed to be a consequence of increased hepatic lipoprotein 
synthesis & decreased clearance. Hyperlipidemia may accelerate atherosclerosis and 
progression of renal disease. 
 
4. Hypercoagulability : -  
• It is mutifactorial: some of the mechanisms are loss of anti-thrombin III in the urine, 
increased fibrinogen production by the liver , increased platelet aggregation.  
• Spontaneous peripheral arterial or venous thrombosis, renal vein thrombosis, and 
pulmonary embolism may occur. 
• Clinical features that suggest acute renal vein thrombosis include sudden onset of flank 
or abdominal pain, gross hematuria, a left-sided varicocele (the left testicular vein drains 
into the renal vein), increased proteinuria, and an acute decline in GFR. Chronic renal vein thrombosis is usually asymptomatic. 
 
5. Other complications:  -  
• Protein malnutrition  
• Iron-resistant microcytic hypochromic anemia due to transferrin loss.  
• Hypocalcemia as a consequence of vitamin D deficiency due to enhanced


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5. Other complications:  -  
• Protein malnutrition  
• Iron-resistant microcytic hypochromic anemia due to transferrin loss.  
• Hypocalcemia as a consequence of vitamin D deficiency due to enhanced 
urinary excretion of cholecalciferol-binding protein.  
• An increased susceptibility to infection from urinary loss and increased 
catabolism of immunoglobulin. 
Diagnosis 
1. Confirming significant proteinuria 
• Quantify 24 hours urine protein 
• Comparing with urinary creatinine level on a single void urine 
• Measurement of urinary protein by a dipstick (+3 or +4 diagnostic if the first two 
are not available)  
2. Renal biopsy ( if available  ): to identify the underlying histopathologic abnormality


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 303• Minimal change diseases: accounts for 80 % nephrotic syndrome in children < 10 
yrs.  
• Membranous glomerulopathy: accounts for 60-70 % of nephrotic syndrome in 
adults. 
• Focal segmental glomerulosclerosis  
Treatment 
The treatment of nephrotic syndrome involves:-  
1. Specific treatment of the underlying morphologic entity 
• Minimal change disease  : Steroids , and cytotoxic drugs  
• Membranous nephropathy : Not steroid responsive 
2. Measures to control proteinuria: - 
a. Dietary protein restriction: the potential value of dietary protein restriction for 
reducing proteinuria must be balanced against the risk of contributing to malnutrition.  
b. Angiotensin-converting enzyme (ACE) inhibitors : decrease proteinuria by 
decreasing glomerular filtration pressure 
c. Controlling hypertension: keeping BP below 130/80 reduces proteinuria. 
3.  Treatment of complications of nephrotic syndrome. 
a. Edema : should be managed cautiously by : 
i. Moderate salt restriction , usually 1 to 2 g/day, and the judicious 
use of  
ii. Loop diuretics  can be given in higher doses: It is unwise to remove 
>1.0 kg of edema per day as more aggressive diuresis may precipitate intravascular volume depletion and prerenal azotemia.   
b. Thromboembolism : Anticoagulation is indicated for patients with deep 
venous thrombosis, arterial thrombosis, and pulmonary embolism. Heparin may not be effective because of urinary loss of anti- thrombin III.


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b. Thromboembolism : Anticoagulation is indicated for patients with deep 
venous thrombosis, arterial thrombosis, and pulmonary embolism. Heparin may not be effective because of urinary loss of anti- thrombin III. 
c. Hyperlipidemia  : may need lipid lowering agents  
d. Vitamin D deficiency : Vit-- D supplementation.


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 304References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Glomerular diseases,  pages 1508-1515 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Glomerular diseases, pages 296-307.


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 3054. Acute Renal Failure  
 
Learning objectives: at the end of this lesson the student will be able to  : 
1. Define acute renal failure. 2. List the etiologies of acute renal failure.   3. Describe the pathophysiology of acute renal failure.   
4. Identify the clinical manifestation of acute renal failure. 
5. Identify complications of acute renal failure. 6. Understand the diagnostic approach of acute renal failure. 7. Understand the principles of management of acute renal failure.  
8. Understand the course and prognosis of acute renal failure.  
9. Refer patients with acute renal failure to hospitals with better facilities  
 Definition:  
Acute renal failure is a syndrome characterized by: 
• Rapid decline in glomerular filtration rate (hours to days ) 
• Retention of nitrogenous wastes due to failure of excretion  
• Disturbance in extracellular fluid volume and 
• Disturbance electrolyte and acid base homeostasis. 
Based on the amount of urine output acute renal failure may be classified as  
• Anuric: - if urine volume is less than 100 ml/day  
• Oliguric:  - if urine volume is less than 400 ml/day  
• Non-oliguric : - if urine volume is greater than or equal 400 ml/day  
Epidemiology: - 
• ARF complicates approximately 5% of hospital admissions and up to 30% of 
admissions to intensive care units. Oliguria (urine output < 400 ml/d) is a frequent 
but not invariable clinical feature (~50%).


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Epidemiology: - 
• ARF complicates approximately 5% of hospital admissions and up to 30% of 
admissions to intensive care units. Oliguria (urine output < 400 ml/d) is a frequent 
but not invariable clinical feature (~50%).  
• ARF is usually asymptomatic and is  diagnosed when biochemical screening of 
hospitalized patients reveals a recent increase in plasma urea and creatinine 
concentrations. 
• Most ARF is reversible, the kidney being relatively unique among major organs in its 
ability to recover from almost complete loss of function.


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Internal Medicine 
 
 306• Nevertheless, ARF is associated with major in-hospital morbidity and mortality, in 
large part due to the serious nature of the illnesses that precipitate the ARF. 
• A prospective study in Ethiopian patients done by Worku Zewdu in 1992, sowed 
that septic abortion was the leading cause of ARF followed by P.falciparum  malaria 
and nephrotoxic agents. 
Acute renal failure may complicate a wide range of diseases, which for purposes of 
diagnosis and management are conveniently divided into three categories 
 
Etiologic classification of acute renal failure   
A. Prerenal ARF  : account for nearly 55 % of all cases of acute renal failure 
I. Hypovolemia 
• Hemorrhage, burns, dehydration 
• Gastrointestinal fluid loss: vomiting, surgical drainage, diarrhea 
• Renal fluid loss: diuretics, osmotic diuresis (e.g., diabetes mellitus), 
hypoadrenalism 
• Sequestration in extravascular space: pancreatitis, peritonitis, trauma, burns, 
severe hypoalbuminemia 
II.  Low cardiac output 
• Diseases of myocardium, valves, and pericardium; arrhythmias; tamponade 
• Other: pulmonary hypertension, massive pulmonary embolus 
III.  Altered renal systemic vascular resistance ratio 
• Systemic vasodilatation: sepsis, anaphylaxis IV. Renal hypoperfusion with 
impairment of renal autoregulatory responses 
• NSAIDS, angiotensin-converting enzyme inhibition  
B. Intrinsic Renal ARF : account for nearly 40% of all ARF


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• Systemic vasodilatation: sepsis, anaphylaxis IV. Renal hypoperfusion with 
impairment of renal autoregulatory responses 
• NSAIDS, angiotensin-converting enzyme inhibition  
B. Intrinsic Renal ARF : account for nearly 40% of all ARF  
I. Renovascular obstruction  (bilateral or unilateral in the setting of one functioning 
kidney) 
II. Disease of glomeruli or renal microvasculature 
III. Acute tubular necrosis 
• Ischemia: as for prerenal ARF (hypovolemia, low cardiac output, renal 
vasoconstriction, systemic vasodilatation), obstetric complications (abruptio placentae, postpartum hemorrhage) 
• Toxins


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 307¾ Exogenous: radio contrast, cyclosporine, antibiotics (e.g., 
aminoglycosides), chemotherapy (e.g., cisplatin), organic solvents (e.g., 
ethylene glycol), acetaminophen, illegal abortifacients 
¾ Endogenous: rhabdomyolysis, hemolysis, ur ic acid, oxalate, plasma cell 
dyscrasia (e.g., myeloma) 
IV. Interstitial nephritis  
Post renal ARF (OBSTRUCTION) : account for  ~5% of ARF. 
I. Ureteric 
• Calculi, blood clot, sloughed papillae, cancer, external compression (e.g., 
retroperitoneal fibrosis) 
II. Bladder neck 
• Neurogenic bladder, prostatic hypertrophy, calculi, cancer, blood clot 
III. Urethra 
• Stricture, congenital valve, phimosis  
Prerenal ARF  
• Prerenal ARF is the most common form of ARF and represents a physiologic 
response to mild to moderate renal hypo perfusion.  
• Prerenal ARF is rapidly reversible upon restoration of renal blood flow and 
glomerular ultrafiltration pressure.  
• More severe hypoperfusion may lead to ischemic injury of renal parenchyma and 
intrinsic renal ARF. Thus, prerenal ARF and intrinsic renal ARF due to ischemia are part of a spectrum of manifestations of renal hypoperfusion.  
• Prerenal ARF can complicate any disease that induces hypovolemia, low cardiac 
output, systemic vasodilatation, or selective renal vasoconstriction. 
Pathophysiology: 
• Hypovolemia  leads to glomerular hypoperfusion, but filtration rate are preserved


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output, systemic vasodilatation, or selective renal vasoconstriction. 
Pathophysiology: 
• Hypovolemia  leads to glomerular hypoperfusion, but filtration rate are preserved 
during mild hypoperfusion through several compensatory mechanisms. During states of more severe hypoperfusion, these compensatory responses are overwhelmed and GFR falls, leading to prerenal ARF. 
• Drugs that interfere with adaptive responses in the renal microcirculation may 
convert compensated renal hypoperfusion into overt prerenal ARF or trigger 
progression of prerenal ARF to ischemic intrinsic renal ARF (ACE-inhibitors, 
NSAIDS)


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 308 
Intrinsic ARF 
• Intrinsic renal ARF can complicate many diverse diseases of the renal parenchyma.  
• Most intrinsic renal ARF is triggered by  ischemia (ischemic ARF) or nephrotoxins 
(nephrotoxic ARF), insults that classically  induce acute tubular necrosis (ATN).  
 
Diagnosis of ARF:  
Careful history is essential  
• Exposure to nephrotoxins and drugs  
• Anuria may indicate post-renal causes  
• Skin rashes may indicate allergic nephritis  
• Evidences of volume depletion: diarrhea, bleeding  
• Pelvic and per-rectal examinati on: look for evidence of abortion  
• Ischemia or trauma to the legs or arms may indicate rhabdomyolysis  
• Recent surgical or radiologic procedures  
• Past and present use of medications   
• Family history of renal diseases  
Physical examination: should be focused to rule out possible differential diagnosis  
Prerenal ARF: is suggested by clinical signs of   
• Intravascular volume depletion ( e.g. orthostatic hypotension , rapid pulse and 
poor skin turgor ) 
• Congestive heart failure (e.g. raised JVP , S3 , dependent edema , and pulmonary 
rales ) 
Acute allergic interstitial nephritis: is suggested by signs of allergy ( e.g. periorbital 
edema, esosinophilia , maculopapular rash , and wheezing ) 
Lower Urinary tract obstruction: is suggested by suprapubic or flank mass or 
symptoms of bladder  dysfunction (e.g. hesitancy, urgency)


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edema, esosinophilia , maculopapular rash , and wheezing ) 
Lower Urinary tract obstruction: is suggested by suprapubic or flank mass or 
symptoms of bladder  dysfunction (e.g. hesitancy, urgency) 
Uremia : - clinical syndrome resulting from the adv erse effect of renal failure on other 
organ systems (only very few develop in acute renal failure)  
 
Complications of ARF 
• Intravascular overload:  may be recognized by weight gain , hypertension , 
elevated central venous pressure ( raise JVP) , Pulmonary edema


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Internal Medicine 
 
 309• Electrolyte disturbance  
o Hyperkalemia:  (serum K+ >5.5 mEq/L) develops as a result of decreased 
renal excretion combined with tissue necrosis or hemolysis. 
o Hyponitremia :  ( serum Na+ concentration < 135 mEq/L ) results from 
excessive water intake in the face of excretory failure 
o Hyperphosphatemia :  ( serum Phosphate concentration of > 5.5 mg /dl ) 
results from failure of excretion or tissue necrosis 
o Hypocalcemia :  ( serum Ca++ < 8.5  mg/dl ) results from decreased Active 
Vit-D , hyperposhphatemia , or hypoalbuminemia 
o Hypercalcemia:  (serum Ca++ > 10.5 mg /dl) may occur during the recovery 
phase following rhabdomyolysis induced acute renal failure. 
• Metabolic acidosis : ( arterial blood PH < 7.35 ) is associated with sepsis or sever 
heart failure 
• Hyperuricemia:  due to decreased uric acid excretion 
• Bleeding tendency :  may occur due to platelet dysfunction and coagulopathy 
associated with sepsis 
• Seizure: may occur related to uremia 
• Chronic Renal failure:  a modest degree of decline in filtration may exist in 10 % 
of patients for several months following ARF. In patients with underlying renal 
diseases who experience ARF , progression to chronic renal failure is relatively 
likely. 
Diagnostic work up  1. Urinalysis: Microscopic evaluation of urinary sediment. 
• Presence of few formed elements or hyaline casts is suggestive of prerenal or 
postrenal azotemia.


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likely. 
Diagnostic work up  1. Urinalysis: Microscopic evaluation of urinary sediment. 
• Presence of few formed elements or hyaline casts is suggestive of prerenal or 
postrenal azotemia. 
• Many RBCs may suggest calculi , trauma , infection or tumor 
• Eosinophilia : occurs in 95 % of patients with acute allergic nephritis  
• Brownish pigmented cellular casts and many renal epithelia cells are seen in 
patients with acute tubular necrosis (ATN ) 
• Pigmented casts without erythrocytes in the sediment from urine but with positive 
dipstick for occult blood indicates hemoglobinuria or myoglobinuria


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Internal Medicine 
 
 310• Dipstick test: trace or no proteinuria with pre-renal and post-renal ARF; mild to 
moderate proteinuria with ATN and moderate to severe proteinuria with 
glomerular diseases.  
• RBCs and RBC casts in glomerular diseases  
• Crystals RBCs and WBCs in post-renal ARF.  
2. Urine and blood Chemistry: most of these tests help to differentiate prerenal 
azotemia, in which tubular reabsorption function is preserved from acute tubular 
necrosis where tubular reabsorption is severely disturbed.  
• Osmolality or specific gravity: decreased in ATN and pos-renal ARF (urine is 
diluted) , while increased in pre-renal ARF ( urine is concentrated .) 
• BUN/plasma creatinine ratio: the BUN/plasma creatinine ratio is normal at 10-15:1 
in ATN, but may be greater than 20:1 in prerenal disease due to the increase in the 
passive reabsorption of urea that follows the enhanced proximal transport of 
sodium and water. Thus, a high ratio is highly suggestive of prerenal disease as 
long as some other cause is not present. But this criterion is not highly specific. 
• Renal failure index: ratio of urine Na+ to urine to plasma creatinine ratio 
(UNa/Ucr/Pcr) . Values less than 1 % are consistent with prerenal ARF ,where as a 
value > 1% indicates ATN 
• Fractional excretion of Na+: is ration of urine-to-plasma Na ratio to urine-to-plasma 
creatinine expressed as a percentage [ (U Na/PNa)/(U cr/Pcr )X 100]. Value below 1%


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value > 1% indicates ATN 
• Fractional excretion of Na+: is ration of urine-to-plasma Na ratio to urine-to-plasma 
creatinine expressed as a percentage [ (U Na/PNa)/(U cr/Pcr )X 100]. Value below 1% 
suggest prerenal failure , and values above 1% suggest ATN 
• Serum K+ and other electrolytes 
3. Radiography/imaging  
• Ultrasonography: helps to see the presence of two kidneys, for evaluating 
kidney size and shape, and for detecting hydronephrosis or hydroureter. It also helps to see renal calculi, and renal vein thrombosis. 
• Retrograde pyelography:  is done when obstructive uropathy is suspected  
 
Management of Acute renal failure: 
1. Prevention :   
• Because there are no specific therapies for ischemic or nephrotoxic ARF, 
prevention is of paramount importance.


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 311• Many cases of ischemic ARF can be avoi ded by close attention to cardiovascular 
function and intravascular volume in high-risk patients, such as the elderly and 
those with preexisting renal insufficiency.  
• Indeed, aggressive restoration of intravascular volume has been shown to reduce 
the incidence of ischemic ARF dramatically after major surgery or trauma, burns, or 
cholera.  
• The incidence of nephrotoxic ARF can be reduced by tailoring the dosage of 
potential nephrotoxins to body size and GFR; for example, reducing the dose or frequency of administration of drugs in pati ents with preexisting renal impairment.  
2. Preliminary measures 
• Exclusion of reversible causes : Obstruction should be relived , infection should 
be treated  
• Correction of prerenal factors : intravascular volume and cardiac performance 
should be optimized  
• Maintenance of urine output : although the prognostic importance of oliguria is 
debated, management of nonoliguric patients is easier. Loop diuretics may be 
usefully to convert the oliguric form of ATN to the nonoliguric form. High doses of 
loop diuretics such as Furosemide ( up to 200 to 400 mg intravenously) may 
promote diuresis in patients who fa il to respond to conventional doses.  
3. Specific Therapies :  
• To date, there are no specific therapies for established intrinsic renal ARF due to 
ischemia or nephrotoxicity.


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promote diuresis in patients who fa il to respond to conventional doses.  
3. Specific Therapies :  
• To date, there are no specific therapies for established intrinsic renal ARF due to 
ischemia or nephrotoxicity.  
• Management of these disorders should focus on elimination of the causative 
hemodynamic abnormality or toxin, avoidanc e of additional insults, and prevention 
and treatment of complications.  
• Specific treatment of other causes of intrinsic renal ARF depends on the underlying 
pathology. 
Prerenal ARF :   
• The composition of replacement fluids for treatment of prerenal ARF due to 
hypovolemia must be tailored according to the composition of the lost fluid.  
• Severe hypovolemia due to hemorrhage should be corrected with packed red blood 
cells, whereas isotonic saline is usually  appropriate replacement for mild to 
moderate hemorrhage or plasma loss (e.g., burns, pancreatitis).


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 312• Urinary and gastrointestinal fluids can vary greatly in composition but are usually 
hypotonic. Hypotonic solutions (e.g., 0.45% saline) are usually recommended as 
initial replacement in patients with prerenal ARF due to increased urinary or gastrointestinal fluid losses, although isotonic saline may be more appropriate in severe cases.  
• Subsequent therapy should be based on measurements of the volume and ionic 
content of excreted or drained fluids. Serum potassium and acid-base status should be monitored carefully.                                                                 
Postrenal ARF:    
• Management of postrenal ARF requires close collaboration between nephrologist, 
urologist, and radiologist.  
• Obstruction of the urethra or bladder neck is usually managed initially by 
transurethral or suprapubic placement of a bladder catheter, which provides temporary relief while the obstructing lesion, is identified and treated definitively.  
• Similarly, ureteric obstruction may be treated initially by percutaneous 
catheterization of the dilated renal pelvis or ureter.  
4. Supportive Measures:  (Conservative therapy ) 
• Dietary management: adequate calorie intake is essential in patients with ARF.  
o Generally, sufficient calorie reflects a diet that provides 40-60 gm of protein 
and 35-50 kcal/kg lean body weight.  
o In some patients, severe catabolism occurs and protein supplementation to


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o Generally, sufficient calorie reflects a diet that provides 40-60 gm of protein 
and 35-50 kcal/kg lean body weight.  
o In some patients, severe catabolism occurs and protein supplementation to 
achieve 1.25 gm of protein /kg body weight is required to maintain nitrogen balance.  
o Restricting dietary protein to approximately 0.6 g/kg per day of protein of 
high biologic value (i.e., rich in essential amino acids) may be recommended 
in sever azotemia.  
• Fluid and electrolyte management  : 
Following correction of hypovolemia, total oral and intravenous fluid administration should be equal to daily sensible losses (via urine, stool, and NG tune o surgical 
drainage ) plus estimated insensible ( i.e. , respiratory and derma ) losses which usually equals 400 – 500 ml/day. Strict input output monitoring is important. 
• Hypervolemia : can usually be managed by restriction of salt and water intake and 
diuretics.


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Internal Medicine 
 
 313• Metabolic acidosis :  is not treated unless serum bicarbonate concentration falls 
below 15 mmol/L or arterial pH falls below 7.2.  
o More severe acidosis is corrected by oral or intravenous sodium 
bicarbonate. Initial rates of replacement are guided by estimates of 
bicarbonate deficit and adjusted thereafter according to serum levels.  
o Patients are monitored for complications of bicarbonate administration such 
as hypervolemia, metabolic alkalosis, hypocalcemia, and hypokalemia.  
o From a practical point of view, most patients requiring sodium bicarbonate 
need emergency dialysis within days.  
• Hyperkalemia: cardiac and neurologic complications may occur if serum K+ level is 
> 6.5 mEq/ L 
o Restrict dietary K+ intake  
o Give calcium gluconate 10 ml of 10% solution over 5 minutes  
o Glucose solution 50 ml of 50 % glucose plus Insulin 10 units IV  
o Give potassium –binding ion exchange resin  
o Dialysis: it medial therapy fails or the patient is very toxic 
• Hyperphosphatemia  is usually controlled by restriction of dietary phosphate and by 
oral aluminum hydroxide or calcium carbonate, which reduce gastrointestinal absorption of phosphate.  
• Hypocalcemia  does not usually require treatment. 
•  Anemia : may necessitate blood transfusion if severe or if recovery is delayed.  
• GI bleeding : Regular doses of antacids appear to reduce the incidence of 
gastrointestinal hemorrhage significantly and may be more effective in this regard


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•  Anemia : may necessitate blood transfusion if severe or if recovery is delayed.  
• GI bleeding : Regular doses of antacids appear to reduce the incidence of 
gastrointestinal hemorrhage significantly and may be more effective in this regard 
than H2 antagonists, or proton pump inhibitors.  
• Meticulous care of intravenous cannulae, bladder catheters, and other invasive 
devices is mandatory to avoid infections 
 
Dialysis  
Indications and Modalities of Dialysis: - Dialysis replaces renal function until regeneration 
and repair restore renal function. Hemodialysis and peritoneal dialysis appear equally effective for management of ARF. Absolute indications for dialysis include: 
¾ Symptoms or signs of the uremic syndrome 
¾ Refractory hypervolemia


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Internal Medicine 
 
 314¾ Sever hyperkalemia 
¾ Metabolic acidosis.  
Clinical course and prognosis 
• Stages: acute renal failure due to ATN typically occurs in three stages: Azotemic , 
Diuretic , and recovery phases. The initial azotemic stage can be either oliguric or 
non oliguric type. 
• Morbidity and mortality: are affected by the presence of oliguria 
o GI bleeding, septicemia, metabolic acidosis and neurologic abnormalities 
are more common in oliguric patients than in nonoliguric patients. 
o The mortality rate for oliguric patients is 50 % where as that of nonoliguric 
patients is only 26 % 
 Prognosis: 
• The mortality rate among patients with ARF approximates 50. It should be stressed, 
however, that patients usually die from sequelae of the primary illness that induced ARF and not from ARF itself 
• Mortality is affected by both severity of the underlying diseases and the clinical 
setting in which acute renal failure occurs 
• E.g. the mortality of ATN is 60 % when it results from surgery or trauma, 30 % when 
it occurs as a complication of medical illnesses, and 10-15 % when pregnancy is involved. 
• Ischemia associated ATN has 2X the mortality risk of nephrotoxic ATN. 
• In agreement with this interpretation, mortality rates vary greatly depending on the 
cause of ARF: ~15% in obstetric patients, ~30% in toxin-related ARF, and ~60% following trauma or major surgery.  
• Oliguria (<400 mL/d) at time of presentation and a rise in serum creatinine of >3


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cause of ARF: ~15% in obstetric patients, ~30% in toxin-related ARF, and ~60% following trauma or major surgery.  
• Oliguria (<400 mL/d) at time of presentation and a rise in serum creatinine of >3 
mg/dl are associated with a poor prognosis and probably reflect the severity of renal injury and of the primary illness.  
• Mortality rates are higher in older debilitated patients and in those with multiple 
organ failure 
• Patients with no complicating factors who survive an episode of acute renal failure 
have a 90 % chance of complete recovery of kidney function.


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Internal Medicine 
 
 315References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Acute 
renal failure, pages 1644-1652. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Acute renal failure, pages 280-284.


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Internal Medicine 
 
 3165. Chronic Renal Failure  
 
Learning objectives: at the end of this lesson the student will be able to  : 
1. Define chronic renal failure. 2. List the etiologies of chronic renal failure.   3. Describe the pathophysiology of chronic renal failure.   
4. Identify the clinical manifestation of chronic renal failure. 
5. Identify common complications of chronic renal failure. 6. Understand the diagnostic approach of chronic renal failure. 7. Understand the principles of management of chronic renal failure.  
8. Understand the course and prognosis of chronic renal failure.  
9. Refer patients with Chronic renal failure to better facilities,  
 Definitions  
Chronic Renal failure : progressive and irreversible reduction of the renal function, over a 
period of more than 6 months, to a level less than 20 % of the normal, as a result of 
destruction of significant number of nephrons.  
• End stage renal disease (ESRD):  represents a clinical state or condition in which 
there has been an irreversible loss of endogenous renal function, of a degree sufficient to render the patient permanently dependent upon renal replacement therapy (dialysis or transplantation) in order to avoid life-threatening uremia. 
• Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ 
systems as a result of untreated or undertreated acute or chronic renal failure. 
• Azotemia  refers to the retention of nitrogenous waste products as renal


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• Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ 
systems as a result of untreated or undertreated acute or chronic renal failure. 
• Azotemia  refers to the retention of nitrogenous waste products as renal 
insufficiency develops. 
 Etiologies  1. Prerenal causes  
• Sever long standing renal artery stenosis 
• Bilateral renal artery embolism 
2. Renal causes  
• Chronic glomerulonephritis: -  primary or secondary forms (30%)


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Internal Medicine 
 
 317• Chronic tubulointerstitial disease:  - vesicouretral reflux, and chronic pyelonephritis 
(in adolescents) 
• Vascular disease:  - hypertensive nephrosclerosis 
• Diabetic nephropathy 
• Connective tissue diseases  : SLE , scleroderma 
• Hereditary disease:  -polycystic kidney disease 
3. Post renal cause  
• Obstructive nephropathy:  - urolithiasis, benign prostatic hypertrophy, 
 
 Chronic glomerulonephritis , Hypertension and diabetic nephropathy are the commonest 
causes for ESRD 
 Stages of Chronic renal failure  
1. Stage of decreased renal reserve  
• Basal glomerular filtration rate (GFR ) may be normal or even elevated (hyper-
filtration). Adaptation increases the function of the remaining nephrons 
• Patients are symptom free  
• BUN and creatinine are normal or slightly elevated.  
2. Stage of Renal insufficiency  
• GFR declines  by 70 %  ( i.e., GFR will be  30% of normal ) 
• Patients may remain asymptomatic  
• Biochemical evidence of the decline in GFR, i.e., rise in serum concentrations of 
urea and creatinine. Early additional clinical and laboratory manifestations of 
renal insufficiency may occur. These may include nocturia, mild anemia and loss 
of energy, decreasing appetite and early disturbances in nutritional status. 
• Sudden stress such as infection, urinary tract obstruction, dehydration, 
administration of nephrotoxic drugs ma y induce signs and symptoms of uremia. 
3. Renal failure  
• GFR falls to below 30% of normal


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• Sudden stress such as infection, urinary tract obstruction, dehydration, 
administration of nephrotoxic drugs ma y induce signs and symptoms of uremia. 
3. Renal failure  
• GFR falls to below 30% of normal 
• An increasing number and severity of uremic clinical manifestations 
• Biochemical abnormalities raised NUN and creatinine.  
4.  End stage renal diseases (ESRD ) 
• GFR falls below 5 to 10% of normal


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 318• Continued survival without renal repl acement therapy becomes impossible. 
 
Pathophysiology 
• Uremic manifestations occur mainly due to accumulation of nitrogenous wastes and 
the reason for accumulation of these wastes is decreased renal excretion and reduced catabolizing capacity of the kidney  
• Most toxins in uremia are by products of proteins and amino acid metabolism, 
because unlike carbohydrates and fats, which are metabolized to CO
2 and H 2O, 
which can be excreted through the lungs and skin , by products of protein are non volatile organic acids  
Clinical manifestations and complications of Chronic Renal failure  
1. Fluid, electrolyte and acid base disturbance 
a) Volume expansion and contraction (edema, dehydration) 
• As long as water intake does not exceed the capacity for free water 
clearance, the extra cellular fluid volume expansion will be isotonic and the patient will remain normonatremic. On the other hand, hyponatremia will be the consequence of excessive water ingestion.  
• Patients with CRF also have impaired renal mechanisms for conserving Na+ 
and H
2O. When an extra renal cause for fluid loss is present (e.g., vomiting, 
diarrhea, sweating, fever), these patients are prone to volume depletion and dehydration.  
• In the face of Sodium intake patients may retain Na
+ and water which may 
lead to congestive heart failure, eripheral edema and ascites . 
b) Potassium Homeostasis:  -


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• In the face of Sodium intake patients may retain Na
+ and water which may 
lead to congestive heart failure, eripheral edema and ascites . 
b) Potassium Homeostasis:  -  
• Most commonly, clinically significant hyperkalemia does not occur until the 
GFR falls to below 10 mL/min 
• Factors that contribute to increased serum K+ level are 
• Endogenous a K+ load (e.g., hemolysis, trauma, infection) or  
• Exogenous K+ (e.g., administration of stored blood, K+-containing 
medications, K+-containing dietary salt substitute).  
• Acidosis : facilitates influx of K+ form ICF to ECF 
• Drugs: potassium sparing diuretics, ACE inhibitors.


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 319c) Metabolic Acidosis:  -  
• Acidosis is a common disturbance during the advanced stages of CRF. With 
advancing renal failure, total urinary net daily acid excretion is usually 
reduced markedly. 
 
2. Renal osteodetrophy and Metabolic bone disease: 
• Is due to disturbance in bone phosphate and calcium metabolism. 
• Hyperphosphatemia is a feature of advanced renal failure. The serum phosphate 
concentration rises in patients with a GFR < 20 mL/min. 
• Calcium : - The total plasma Ca2+ concentration in patients with CRF is often 
significantly lower than normal. Patients with CRF tolerate the hypocalcaemia quite well; rarely is a patient symptomatic from the decreased Ca
2+ 
concentration. Note that the low serum level of Ca++ is attributed to secondary 
hyperparathyroidism. 
• Reduced synthesis of 1,25 (OH)2D3 during CRD plays a key role in the 
pathogenesis of hyperparathyroidism, both directly and through hypocalcaemia. The abnormal vitamin D metabolism may be related to the renal disease itself 
(since the active vitamin D metabolite is normally produced in the proximal 
tubule) and to the hyperphosphatemia, which has a suppressive effect on the renal 1α-hydroxylase enzyme.  
Some of the resulting bony abnormalities are  
o Ostitis fibrosa cystica  : is due to osteoclastic bone resorption of 
specially  terminal phalanges , long bones and distal end of clavicle  
o Renal rickets  ( Osteomalacia )


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Some of the resulting bony abnormalities are  
o Ostitis fibrosa cystica  : is due to osteoclastic bone resorption of 
specially  terminal phalanges , long bones and distal end of clavicle  
o Renal rickets  ( Osteomalacia ) 
o Osteosclerosis  : enhanced bone density in the upper and lower margins 
of vertebrae 
3. Cardiovascular complications  
a) Congestive heart failure and/or pulmonary edema  : it may be due to 
• Volume over load  
• Increase pulmonary capillary permeability 
b) Hypertension :  
• Is the most common complication of end stage renal disease.  
• It results from fluid overload.


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 320• Sometimes sever form of hypertension may occur. 
c) Pericarditis:  metabolic toxins are responsible for pericarditis. 
• The finding of a multicomponent friction rub strongly supports the 
diagnosis 
• The pericardial effusion is often hemorrhagic  
4. Hematologic abnormalities :  
a) Normocytic normochromic anemia : which may be severe ( Hgb 4-6 gm/dl) 
  The cause of anemia is multifactorial 
• Decreased synthesis of erythropoietin (the most important factor ) 
• Toxins suppressing bone marrow function 
• Blood loss ( mainly GI blood loss ) 
• Decreased life span of RBC 
b) Bleeding tendency  : attributed to platelet dysfunction 
• Patients may manifest with bleeding and easily bruiseablity 
• GI bleeding  
• Intracranial hemorrhage  
c) Susceptibility to infection : is due to  
• Change in leukocyte formation and function  
• Lymphocytopeneia and atrophy of lymphoid tissue  
5. Neuromuscular abnormalities  
Early stage : irritability, inability to concentrate drowsiness, insomnia  
Intermediate stage:  
• Mild behavioral change , poor judgment  
• Neuromuscular irritability: hiccup , cramps  , fasciculation , twitching of muscles 
Terminal stage:  
• Asterixis, myoclonus, chorea, seizure  
• Stupor which may even lead to coma 
• Peripheral neuropathy : distal sensory polyneuropathy  
o Restless leg syndrome : ill defined sensation of discomfort on the legs  
6. Gastro intestinal abnormalities


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• Stupor which may even lead to coma 
• Peripheral neuropathy : distal sensory polyneuropathy  
o Restless leg syndrome : ill defined sensation of discomfort on the legs  
6. Gastro intestinal abnormalities  
• Early symptoms : anorexia , hiccup , nausea and vomiting  
• Uremic fetor: the patient’s breathe smells like urine.  
• Mucosal ulceration leads to GI bleeding and peptic ulcer diseases.


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 3217. Endocrine and Metabolic abnormalities  
• Hypogonadism is common  
o In men : decreased plasma testosterone level , impotence m oligospermia  
o In women: amenorrhea, inability to carry pregnancy to term. 
8. Dermatologic abnormalities ; 
• Pallor due to anemia  
• Echymosis, hematoma  
• Pruritis, and excoriation (Ca++ deposits and 20 hyperparathyroidism) 
• Yellowish declaration of skin : urochromes  
• Uremic frost: is seen in advanced uremia  
o It is due to high concentration of urea in the sweat, and after evaporation of 
the sweat, a fine white powder can be found on the skin surface. 
 
Diagnostic approach 
Differentiate acute from chronic renal failure : the following findings characterize CRF   
• Reduced kidney size on ultrasonography 
• Long standing nocturia and pruritis 
• Finding of broad tubular casts on urine analysis 
• Anemia (not always) 
• Renal osteodystrophy 
Identification of aggravating factors (acute or chronic)  
• Hypovolemia or hypotension 
• Hypertension  
• Congestive heart failure 
• Sepsis 
• Nephrotoxins 
 
Evaluation of reversible underlying etiology 
• Malignant hypertension 
• Obstructive uropathy 
• Systemic lupus erythematosis


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 322Establishing the underlying cause  
History  
• Of special importance in establishing the etiology of CRF are a history of: 
o Hypertension 
o Diabetes mellitus  
o Systemic infectious or  inflammatory diseases  
o Metabolic diseases 
o Exposure to drugs and toxins 
o Family history of renal and urologic disease.  
• In evaluating the uremic syndrome, questions about appetite, diet, nausea, and vomiting, 
hiccoughing, shortness of breath, edema, weight change, muscle cramps, bone pain, 
mental acuity, and activities of daily living are especially helpful. 
 
Physical Examination:  -  
• Particular attention should be paid to: 
• Blood pressure 
• Funduscopy 
• Precordial examination 
• Examination of the abdomen for bruits and palpable renal masses 
• Extremity examination for edema 
• Neurologic examination for the presence of asterixis, muscle weakness, and 
neuropathy  
• In addition, the evaluation of prostate size in men and potential pelvic masses in 
women should be undertaken by appropriate physical examination. 
Diagnostic work up   
• These should also focus on a search for clues to an underlying disease process and 
its continued activity.  
• Other tests to determine the severity and chronicity of the disease include : 
o Serial measurements of serum creatinine and blood urea nitrogen 
• Hemoglobin 
• Electrolytes : calcium, phosphate, and alkaline phosphates to assess metabolic 
bone disease.  
• Urinalysis:


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 323o May be helpful in assessing the presence of ongoing activity of the underlying 
inflammatory or proteinuric disease process, and when indicated should be 
supplemented by a 24-h urine collection for quantifying protein excretion.  
o The presence of broad casts on examination of the urinary sediment is a 
nonspecific finding seen with all diverse etiologies and reflects an advanced stage of CRF.  
• Ultrasonography of kidneys:  
o An ultrasound examination of the kidneys verifies the presence of two 
symmetric kidneys, provides an estimate of kidney size, and rules out renal 
masses and obstructive uropathy.  
o The documentation of symmetric sma ll kidneys supports the diagnosis of 
progressive CRF with an irreversible component of scarring. The occurrence of normal kidney size suggests the possibility of an acute rather than chronic process. However in some diseases, chronic renal failure may be present with normal sized or even enlarged kidneys. E.g.  Amyloidosis , polycystic 
kidney diseases , Diabetic nephropathy 
 
Management of chronic renal failure  The general management of the patient with chronic 
renal disease involves the following issues 
 
1) Treatment of reversible causes of renal dysfunction 
2) Preventing or slowing the progression of renal disease 3) Treatment of the complications of renal dysfunction 4) Identification and adequate preparation of the patient in whom renal replacement 
therapy will be required


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2) Preventing or slowing the progression of renal disease 3) Treatment of the complications of renal dysfunction 4) Identification and adequate preparation of the patient in whom renal replacement 
therapy will be required 
 
1. Treating reversible causes of renal dysfunction  – In addition to exacerbation of 
their original renal disease, patients with chronic renal disease, with a recent decrease in renal function may be suffering from an underlying reversible process 
such as : 
o Hypotension or dehydration  
o Administration of nephrotoxic drugs  
o Urinary tract obstruction


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 324o Sever hypertension 
o Infection  
• Correcting these reversible causes can improve the renal function. 
2. Slowing the rate of progression  of renal diseases :  
• Angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor 
blockers (ARBs) slows the progre ssion of chronic renal failure .  
• Blood pressure control : decreases progression of CRF 
Target BP for patients with: 
¾ Proteinuria is 125/75 mmHg  
¾ for patients without proteinuria is 130/85 mmHg  
• The possible efficacy of dietary protein restriction, in slowing progression 
of renal diseases, is less clear.   
 
3. Treatment of the complications of renal dysfunction  : 
a) Volume overload  – 
• Dietary sodium restriction  
• Diuretic therapy, usually with a loop diuretic given daily.  
b) Hyperkalemia : 
• Low-potassium diet or concurrent use of a loop diuretic (to increase urinary 
potassium losses) often ameliorates the degree of hyperkalemia. 
• Calcium gluconate ; 10 ml of 10% solution over 5 minutes  
• Glucose plus insulin:  
• Correction of acidosis : administration of bicarbonate  
• Potassium exchange resins: Kayaxalate  
 
c) Metabolic acidosis : 
• Alkali therapy is advocated to maintain the plasma bicarbonate 
concentration above 22 mEq/L. If alkali is given, sodium bicarbonate (in a 
daily dose of 0.5 to 1 mEq/kg per day) is the agent of choice. 
d) Hyperphosphatemia: 
• Dietary phosphate restriction may limit the development of secondary


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concentration above 22 mEq/L. If alkali is given, sodium bicarbonate (in a 
daily dose of 0.5 to 1 mEq/kg per day) is the agent of choice. 
d) Hyperphosphatemia: 
• Dietary phosphate restriction may limit the development of secondary 
hyperparathyroidism in patients with chronic renal failure. An intake of


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 325about 800 mg/day may be desirable but can be accomplished only by 
limiting protein intake. 
 
 
e) Hypertension : 
• Salt restriction 
• Diuretics: loop diuretics are recommended for the treatment of 
hypertension and edema in patients with chronic renal failure. Thiazide 
diuretics have additive effect when administered with a loop diuretic for 
refractory edema.  
• Anti hypertensive drugs  
f) Anemia : 
• Blood transfusion in selected patients  
• Recombinant Erythropoietin may be given. 
g) Malnutrition: 
• The desire to maintain adequate nutrition among patients with chronic 
renal failure clearly competes with attempts to slow the progression of 
renal dysfunction with the use of a low protein diet.  
• Although the benefits of slowing progressive renal failure with marked 
dietary protein restriction remain controversial, it is probably reasonable to restrict intake to 0.8 to 1.0 g/kg of high biologic value protein (plant source) 
• Since this level of restriction avoids protein malnutrition and may slow 
progressive disease. Overall, the diet of most patients with chronic renal failure should provide approximately 30 to 35 kcal/kg per day.  
 
4. Preparation for renal replacement Therapy 
o Education  
o Informed choice of renal replacement therapy 
i. Chronic Hemodialysis 
ii. Kidney transplantation


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 326References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Chronic renal failure, pages 1653-1662. 
2) Myers R. Allen , National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Chronic renal failure, pages 285-286.


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 3276. Urinary Tract infection  
 
Learning Objective :  At the end of this unit the student will be able to  
1. Define urinary tract infections.    
2. List the etiologies of urinary tract infections.      
3. Describe the epidemiology of urinary tract infections.  
4. Explain the pathogenesis of urinary tract infections.     5. Describe the clinical features of urinary tract infections.     6. List the common complications urinary tract infections.  
7. Describe the most commonly used tests for the diagnosis of urinary tract infections.      
8. Make an accurate diagnosis of urinary tract infections.       9. Treat urinary tract infections with appropriate antibiotics.   10. Design appropriate methods of prevention and control of urinary tract infections.     
 
Definitions 
UTI: is an acute infection of the urinary tract, and is subdivided into two general anatomic 
categories:  
• Lo wer urinary tract infection: which includes urethritis and cystitis and  
• Upper urinary tract infection: includes acute pyelonephritis, prostatitis, and intrarenal and perinephric abscesses).   
 
From a microbiologic perspective, urinary tract infection (UTI)  
• Exists when pathogenic microorganisms are detected in the urine, urethra, bladder, 
kidney, or prostate. In most instances, growth of more than 10
5 organisms per milliliter 
from a properly collected midstream "clean-catch" urine sample indicates infection.


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kidney, or prostate. In most instances, growth of more than 10
5 organisms per milliliter 
from a properly collected midstream "clean-catch" urine sample indicates infection. 
• Especially in symptomatic patients, a smaller number of bacteria (102 to 104/mL) may 
signify infection.  
• In urine specimens obtained by suprapubic aspiration or "in-and-out" catheterization and 
in samples from a patient with an indwelling catheter, colony counts of 102 to 104/mL 
generally indicate infection.  
Recurrence of UTI after treatment 
• Infections that recur after antibiotic therapy can be due to the persistence of the 
originally infecting strain (as judged by species, antibiogram, serotype, and molecular


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 328type) that become evident within 2 weeks of cessation of therapy termed relapse, or to 
reinfection with a new strain that become evident after 2 weeks of cessation of therapy. 
 
Chronic pyelonephritis : refers to chronic interstitial nephritis believed to result from bacterial 
infection of the kidney. Manifested by calyceal dilatation & cortical scarring.  
 
Acute Urinary tract infection  
Epidemiology  
Epidemiologically, UTIs are subdivided into: 
1. Non-catheter-associated (or community-acquired) infections.  
2. Catheter-associated (or nosocomial) infections and  
• The vast majority of acute symptomatic infections involve young women.  
• Acute symptomatic UTIs are unusual in men under the age of 50.  
• The development of asymptomatic bacteriuria parallels that of symptomatic infection and is 
rare among men under 50 but common among women between 20 and 50.  
• Asymptomatic bacteriuria is more common among elderly men and women, with rates as 
high as 40 to 50% in some studies.  
• A study done by Messele Gedebou in 1980’s showed that among patients with bacteruria E. 
coli was identified in 80% of the patients with symptomatic UTI, in Ethiopia.  
 
Etiology 
1. Etiologic agents for community acquired cases 
• Commonest causes are E. coli (80%), S. saprophyticus(10%), Klebsiella 
pneumoniae (5%) and other (5%)


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coli was identified in 80% of the patients with symptomatic UTI, in Ethiopia.  
 
Etiology 
1. Etiologic agents for community acquired cases 
• Commonest causes are E. coli (80%), S. saprophyticus(10%), Klebsiella 
pneumoniae (5%) and other (5%) 
• In acute uretheral syndrome (Sexually transmitted organisms: N. gonorrhea, Chlamydia trachomitis, Trichomonas, Candida, and herpes 
simplex virus may cause lower UIT) 
• In elderly Enterococcus fecalis may be a cause for UTI. 
• Bacteremia is often due to S. aureus. 
2. Hospital acquired/ catheter associated UTI 
• E. coli (30%) 
• Enterococci (15%) 
• Pseudomonas (10%)


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 329• S. aureus, yeasts, and other Enterobacteriacea 
 
Pathogenesis and source of infection 
Routs of inoculation  
• Urethral inoculation : The urinary tract should be viewed as a single anatomic unit that 
is united by a continuous column of urine ex tending from the urethra to the kidney. In the 
vast majority of UTIs, bacteria gain access to the bladder via the urethra. Ascent of 
bacteria from the bladder may follow and is probably the pathway for most renal parenchymal infections. Whether bladder infection ensues depends on interacting effects of the pathogenicity of the strain, the inoculum size, and the local and systemic 
host defense mechanisms. 
 
• Hematogenous spread: pyelonephritis occurs most often in debilitated patients who are 
either chronically ill or receiving immunos uppressive therapy. Metastatic staphylococcal 
or candidal infections of the kidney may follow bacteremia or fungemia, spreading from 
distant foci of infection in the bone, skin, vasculature, or elsewhere. 
 
Conditions affecting pathogenesis /risk factors for UTI 
1. Gender and Sexual Activity:  
• The female urethra appears to be particularly prone to colonization with colonic


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distant foci of infection in the bone, skin, vasculature, or elsewhere. 
 
Conditions affecting pathogenesis /risk factors for UTI 
1. Gender and Sexual Activity:  
• The female urethra appears to be particularly prone to colonization with colonic 
gram-negative bacilli because of its proximity to the anus, its short length (about 4 cm), and its termination beneath the labia. Sexual intercourse causes the introduction of bacteria into the bladder and is temporally associated with the onset of cystitis; it thus appears to be important in the pathogenesis of UTIs in younger 
women.  
• In males who are <50 years old and who have no history of heterosexual or 
homosexual rectal intercourse, UTI is exceedingly uncommon, and this diagnosis 
should be questioned in the absence of clear documentation.  
• An important factor predisposing to bacteriuria in men is urethral obstruction due to 
prostatic hypertrophy.  
• Men (and women) who are infected with HIV and who have CD4+ T cell counts of 
<200/μL are at increased risk of both bacteriuria and symptomatic UTI.


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 330• Finally, lack of circumcision has been ident ified as a risk factor for UTI in both 
neonates and young men. 
 
2. Pregnancy :  
• Is clearly associated with altered uretheral smooth muscle function and higher 
incidence of asymptomatic bacteriuria and 20 to 30% of pregnant women with 
asymptomatic bacteriuria subsequently develop pyelonephritis. 
• UTIs are detected in 2 to 8% of pregnant women. Symptomatic upper urinary tract 
infections, in particular, are unusually common during pregnancy.  
• Bladder catheterization during or after delivery causes additional infections. 
Increased incidences of low-birth-weight infants, premature delivery, and newborn mortality result from UTIs during pregnancy, particularly those infections involving the upper tract. 
 
3. Vesicoureteral reflux:  
• Defined as reflux of urine from the bladder cavity up into the ureters and 
sometimes into the renal pelvis.  
• Vesicoureteral reflux occurs during voiding or with elevation of pressure in 
the bladder.  
• Vesicoureteral reflux is common among children with anatomic 
abnormalities of the urinary tract as well as among children with anatomically normal but infected urinary tracts. In the latter group, reflux disappears with advancing age and is probably attributable to factors other 
than UTI.  
• Vesicoureteral reflux may promote ascending infection in several ways, including


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than UTI.  
• Vesicoureteral reflux may promote ascending infection in several ways, including 
increased delivery of bacteria  , increased size of inoculum , incomplete bladder emptying  
4.  Obstruction : Any impediment to the free flow of urine caused tumor, stricture, stone, or 
prostatic hypertrophy results in hydronephrosis. This results in urinary stasis and impairs 
host defense,  which  greatly increased the frequency of UTI.  
5. Neurogenic Bladder Dysfunction:  - Interference with the nerve supply to the bladder, 
as in spinal cord injury, tabes dorsalis, multiple sclerosis, diabetes, and other diseases, 
may be associated with UTI.


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 3316. Diabetes mellitus:  is associated with high rate of infection. Part of the risk is mediated 
through neurogenic bladder disturbance, and partly due to other immune disorders in 
diabetes. 
7. Immune deficiency:  congenital, acquired or drug induced immunodeficiencies are 
associated with increased susceptibility to infection. 
8. Bacterial Virulence Factors : - Not all strains of E. coli are equally capable of infecting 
the intact urinary tract. Bacterial virulence factors markedly influence the likelihood that a 
given strain, once introduced into the bladder, will cause UTI.  
9.  Genetic Factors:  increasing evidence suggests that host genetic factors 
influence susceptibility to UTI. A maternal history of UTI is more often found 
among women who have experienced recurrent UTIs than among controls. 
 
Clinical presentation  
Cystitis:  
• Patients with cystitis usually report dysuria, frequency, urgency, and suprapubic 
pain.  
• The urine often becomes grossly cloudy and malodorous, and it is bloody in about 
30% of cases. 
• If a genital lesion or a vaginal discharge is evident, then pathogens that may cause 
urethritis, vaginitis, or cervicitis, such as C. trachomatis, N. gonorrhoeae, 
Trichomonas,  Candida,  and herpes simplex virus , should be considered. 
Acute Pyelonephritis :  
• Symptoms of acute pyelonephritis generally develop rapidly over a few hours or a 
day and include a fever, shaking chills, nausea, vomiting, and diarrhea.


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Acute Pyelonephritis :  
• Symptoms of acute pyelonephritis generally develop rapidly over a few hours or a 
day and include a fever, shaking chills, nausea, vomiting, and diarrhea.  
• Symptoms of cystitis may or may not be present.  
• Physical examination:  fever, tachycardia, and generalized muscle tenderness, 
marked tenderness on deep pressure in one or both costovertebral angles or on deep abdominal palpation ( Costvertebral angle tenderness ).  
• In some patients, signs and symptoms of gram-negative sepsis predominate.  
Urethritis :  
• Approximately 30% of women with acute dysuria, frequency, and pyuria have 
midstream urine cultures that show either no growth or insignificant bacterial growth.


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 332• Clinically, these women cannot always be readily distinguished from those with 
cystitis. In this situation, a distinction should be made between women infected with 
sexually transmitted pathogens, such as C. trachomatis, N. gonorrhoeae, or herpes simplex virus, and those with low-count E. coli or staphylococcal infection of the urethra and bladder.  
• Chlamydial or gonococcal  infection should be suspected in women with a gradual 
onset of illness, no hematuria, no suprapubic pain, and more than 7 days of symptoms.  
• The additional history of a recent sex-partner change, especially if the patient's 
partner has recently had chlamydial or gonococcal urethritis, should heighten the suspicion of a sexually transmitted infection, as should the finding of mucopurulent 
cervicitis.  
• Gross hematuria, suprapubic pain, an abrupt onset of illness, a duration of illness of 
<3 days, and a history of UTIs favor the diagnosis of  E. coli UTI.  
 
Catheter-Associated UTIs :  
• Bacteriuria develops in at least 10 to 15% of hospitalized patients with indwelling 
urethral catheters. The risk of infection is about 3 to 5% per day of catheterization.  
• Clinically, most catheter-associated infections cause minimal symptoms and no 
fever and often resolve after withdrawal of the catheter.  
• Gram-negative bacteremia, which follows catheter-associated bacteriuria in 1 to 2% 
of cases, is the most significant recognized complication of catheter-induced UTIs.


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fever and often resolve after withdrawal of the catheter.  
• Gram-negative bacteremia, which follows catheter-associated bacteriuria in 1 to 2% 
of cases, is the most significant recognized complication of catheter-induced UTIs.  
• The catheterized urinary tract has repeatedly been demonstrated to be the most 
common source of gram-negative bacteremia in hospitalized patients, generally 
accounting for about 30% of cases. 
 
Diagnostic work up  
1. Urinalysis: 
• Urinary sediment :  
• Leukocytes are found in the urine : > 5 WBCs/ high power field in centrifuged urine 
or > 10 WBCs/ higher power field in unspun urine suggests UTI 
• Microscopic bacteruria: single microorganism per oil immersion field of unspun urine 
is indicative of a colony growth on culture of more than 10
5 colonies /ml.


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 333• Gram stain of urethral discharge may be help full in patients suspected of having 
STI associated urethritis. 
2. Culture of the urine:  is a definitive means for diagnosis 
• A clean catch , mid stream urine specimen should be collected 
• The growth  of more than 105 colonies /ml in the presence of symptoms signifies 
infection that needs treatment  
3.  Blood:  increased WBCs in the blood  
4. Radiologic urologic evaluation:  may be help full in identification of some 
predisposing conditions such as urolithiasis, BPH, vesicoureteral reflux  
 
Therapy  
The following principles underlie the treatment of UTIs: 
1. Except in acute uncomplicated cystitis in women, a quantitative urine culture, rapid 
diagnostic test should be performed to confirm infection before treatment is begun.  
2. Factors predisposing to infection, such as obstruction and calculi, should be 
identified and corrected if possible. 
3. Relief of clinical symptoms does not always indicate bacteriologic cure. 
4. In general, uncomplicated infections confined to the lower urinary tract respond to 
short courses of therapy, while upper trac t infections require longer treatment 
• The anatomic location of a UTI greatly influences the success or failure of a 
therapeutic regimen. Bladder bacteriuria (cystitis) can usually be eliminated with nearly any antimicrobial agent to which the infecting strain is sensitive.


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• The anatomic location of a UTI greatly influences the success or failure of a 
therapeutic regimen. Bladder bacteriuria (cystitis) can usually be eliminated with nearly any antimicrobial agent to which the infecting strain is sensitive. 
• Treatment of pyelonephritis  – Treatment decisions include whether or not to 
hospitalize the patient, which therapy to  administer empirically, and when to order 
imaging studies to determine whether an infection is complicated  
 
Decision to hospitalize : Indications for admission to the hospital in acute pyelonephritis  
1. Inability to maintain oral hydration or take medications 2. Concerns about patient compliance 3. Uncertainty about the diagnosis 4. Severe illness with high fevers, pain, and marked debility 
Empiric antibiotic choices  – 
o The initial antibiotic therapy is selected on the basis of urinalysis and an 
understanding of epidemiology and bacteriology of the infection.


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 334o Knowledge of the antimicrobial susceptibility profile of uropathogens in the 
community helps to guide therapeutic decisions. 
o Ampicillin and sulfonamides should not be used for empiric therapy because of the 
high rate of resistance among causative uropathogens.  
o In comparison, resistance to the fluoroquinolones and aminoglycosides is very low 
in uncomplicated UTIs and Aminoglycosi des and fluoroquinolones achieve higher 
tissue levels. So these drugs are preferred for empiric treatment.  
o All pregnant women should be screened for bacteriuria in the first trimester and 
should be treated if bacteriuria is demonstrated. 
1. Acute Uncomplicated lower UIT in women :  may be treated with  
• Trimethoprim –Sulfamethoxazol : 480 mg 2 tabs PO BID for 3-5 days 
• Norfloxacin 400 PO BID or Ciprofloxacin 500 mg PO BID for 5-7 days  
2. Acute uncomplicated pyelonephritis in women  : E. coli , P. mirabilis , S. saprophyticus 
are the common causes  
• Norfloxacin 400 PO BID or Ciprofloxacin 500 mg PO BID for 7-14 days or  
• Single dose of Ceftriaxon 1gm or Gentamicin 80 mg IV followed by 
Trimethoprim –Sulfamethoxazol : 480 mg 2 tabs PO BID for 14 days 
3. Complicated UTI in men and women:  E. coli , Proteus , Klebsiella , Pseudomonas , 
Serratia , enterococci, staphylococci are the common etiologies.  
• Mild to moderate illness, no nausea or vomiting: outpatient therapy 
• Norfloxacin 400 PO BID or Ciprofloxacin 500 mg PO BID for 10-14 days or


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Serratia , enterococci, staphylococci are the common etiologies.  
• Mild to moderate illness, no nausea or vomiting: outpatient therapy 
• Norfloxacin 400 PO BID or Ciprofloxacin 500 mg PO BID for 10-14 days or 
4. Severe illness or possible urosepsis: hospitalization is required . 
• Ceftriaxone 1gm IV daily or BID  
• Gentamicine 80 mg IV TID  
• Ampicillin  1gm IV QID and then 500 mg IV QID 
• IV quinolones such as Ciprofloxacin 200-400 mg IV BID can also be used if 
available  
• If enterococcus is suspected based upon the Gram stain, ampicillin (1 to 2 g IV 
Q6h) plus gentamicin (1.0 mg/kg IV Q8h or adjusted for renal function). 
Note:  IV medication should be changed to PO as soon as the patient became afebrile and 
then give PO TMP-SMX or Ciprofloxacin or Norfloxacin   for 10- 21 days.  
Parenteral therapy – For hospitalized patients, aminoglycosides (3 to 5 mg/kg) given once 
daily are cost effective , associated with low toxicity when used for short durations, and


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 335may provide a therapeutic advantage compared with beta lactams, because of their marked 
and sustained concentration in renal tissue .  
Urologic evaluation .  
• Routine urologic investigation of young healthy women with acute uncomplicated 
pyelonephritis is generally not recommended.  
• Urologic consultation and evaluation of the upper urinary tract with an ultrasound 
should be considered if the patient remains febrile or has not shown signs of 
demonstrable clinical improvement after 72 hours of treatment to rule out the 
presence of obstruction, renal or perinephric abscesses, or other complications of 
pyelonephritis.  
• It is reasonable to perform a urologic evaluation, starting with renal ultrasound to 
rule out nephrolithiasis or obstructive uropathy, after two recurrences of pyelonephritis or if any complicating factor is identified.  
Prognosis 
• In patients with uncomplicated cystitis or  pyelonephritis, treatment ordinarily results 
in complete resolution of symptoms. When repeated episodes of cystitis occur, they are nearly always reinfections, not relapses. 
• Acute uncomplicated pyelonephritis in adults rarely progresses to renal functional 
impairment and chronic renal disease. Repeated upper tract infections often represent relapse rather than reinfection, and a vigorous search for renal calculi or an underlying urologic abnormality should be undertaken. If neither is found, 6


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impairment and chronic renal disease. Repeated upper tract infections often represent relapse rather than reinfection, and a vigorous search for renal calculi or an underlying urologic abnormality should be undertaken. If neither is found, 6 
weeks of chemotherapy may be useful in eradicating an unresolved focus of 
infection. 
• Repeated symptomatic UTIs in children and in adults with obstructive uropathy, 
neurogenic bladder, structural renal disease, or diabetes may progress to chronic renal disease with unusual frequency. Asymptomatic bacteriuria in these groups as well as in adults without urologic disease or obstruction predisposes to increased numbers of episodes of symptomatic infection but does not result in renal 
impairment in most instances.


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Internal Medicine 
 
 336References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Urinary tract infection and pyelonephritis ,  pages 1715-1721. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Urinary tract infection, Pages 284-285.


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Internal Medicine 
 
 337CHAPTER FIVE 
DISEASES OF THE GASTRO INTESTINAL SYSTEM 
 
1. Approach to a patient wi th gastrointestinal disorder 
 
Learning objectives: at the end of this unit the student will be able to 
1. List the symptoms of gastrointestinal diseases  
2. Characterize each symptom of gastrointestinal diseases 
3. Describe the investigations for gastrointestinal diseases 4. Outline the steps in paracentesis 5. Describe the difference between exudates and transudates and their clinical use 6. List the different radiological and endoscopic investigations and their clinical use 
Patients with gastrointestinal disorders may present with a variety of symptoms that are specific to the gastrointestinal tract and/or general systemic symptoms. Disorders of the gastrointestinal tract also give a variety of signs. 
 
Common symptoms include:  
• Abdominal pain, abdominal distension  
• Dyspepsia 
• Diarrhea or constipation  
• Gastrointestinal bleeding    
• Jaundice      
• Change in weight and change in appetite  
• Nausea vomiting  
• Change in stool color 
• During history taking, detailed analysis of the above symptoms should be done, 
and history of medications should also be elicited.  
• The usual techniques and steps of physica l examination of the gastrointestinal 
system should be followed, that include: inspection, auscultation, percussion, and 
palpation


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 338Diagnostic work up of patients  with gastrointestinal diseases 
1) Stool microscopy  for i ntestinal parasite; ova, cyst or trophozoites, pus cells and red 
blood cells 
2) Stool culture  - indicated in certain cases of infectious diarrhea  
3) Chemical analysis of stool  test for fecal fat and occult blood  
4) Aspiration of peritoneal fluid (abdominal paracentesis) could be:- 
• Diagnostic  – for evaluation of clinically evident ascites  
• Therapeutic  – to remove fluid in case of refractory ascites with respiratory 
embarrassment.  
Technique  
ο Empty the urinary bladder 
ο Patient lying flat or slightly probed up  
ο Give local anesthetics if available 
ο Site of aspiration is the right iliac fossa, a little outside the midpoint of a 
line joining the umbilicus to anterior superior iliac spine. 
ο For diagnostic purpose 10cc syringe may be used  
ο For therapeutic purpose trocar and flanged cannula are used. If this is not 
available intravenous set with needle may be used. 
The fluid is analyzed biochemically, bacteriol ogically, cytologically and physically.  
ο Biochemical – protein, glucose, Lactate dehydrogenase (LDH) 
ο Bacteriology   – Gram staining, AFB staining  
ο Culture  
ο Cytology – cell count and differential; look for malignant cells 
ο Physical – color, specific gravity  
Based on the above analysis, ascites is classi fied into two: exudative and transudative, and 
the main differences are outlined below:


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 339Table V-1-1, Main differences between exudative and transudative ascetic fluids  
 
 Exudative  Transudative  
Specific gravity  > 1.018  < 1.018  
Protein  > 2.5 gm/dl  < 2.5 gm/dl  
Serum ascetic 
albumin gradient)  < 1.1                         > 1.1 
 
Causes  Bacterial peritonitis  
TB peritonitis  
Malignancy  CHF  
Cirrhosis  
Nephrotic syndrome  
 
5) Radiology of the gastrointestinal tract  
• Plain x-ray  –   no contrast is used and can be taken erect (to see for air fluid level) 
or supine.  
• Contrast x-rays  – barium is used to outline the lumen of the gastrointestinal tract. 
Different terminologies are used to describe barium studies of the different parts of the gastrointestinal tract:   
o For esophagus - Barium swallow.  
o For stomach     - Barium meal. 
o For intestine     - Barium meal and follow through.  
o For Rectum      -  Barium enema     
• Indications for x-ray of the GI tract include  
o Intestinal obstruction (plain films) 
o Dysphagia 
o Peptic ulcer disease 
o Inflammatory bowel disease 
6) Endoscopy is visualization of the lumen of the GI tract with endoscope. 
Endoscopes are of two types depending their flexibility  
ο Rigid  used for removal of foreign body  
ο Fibro-optic  is flexible and used for visualization of the GI tract 
Depending on the structures to be visualized endoscopes can be divided into  
A) Upper GI endoscopy:-   
o It is used to visualize structures up to the second part of the duodenum.


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 340o It can be used for diagnostic and therapeutic purposes (to stop bleeding 
varices, ulcers, or to dilate esophageal strictures) 
B) Lower GI endoscopy: there are three different types of lower GI 
endoscopies, to visualize the different parts of the large intestine:  
o Colonoscopy : for diagnosis and management of colonic polyps and 
ulcers 
o Sigmoidoscopy : to visualize the sigmoid colon.  
o Proctoscopy : to visualize the rectum and anus. 
 
 
Diagnostic work up of patients wit h diseases of hepatobiliary system  
1. Biochemical tests: 
• Tests for the detoxification capacity of the liver : 
ο Serum ammonia level 
ο Serum bilirubin, urine bilirubin level 
• Tests for synthetic function of the liver:  
ο Serum albumin level 
ο Prothrombin time  
• Tests indicating hepatocellular damage  
ο Transaminases (serum glutamic oxalate transferase (SGOT) and serum 
glutamic pyruvate transferase (SGPT)) 
• Tests which show cholestasis  
ο Alkaline phosphatase 
ο (Direct) bilirubin level. 
2. Ultrasound  is a noninvasive procedure that may be help full in diagnosing the following 
diseases: 
o Cirrhosis     
o Metastasis  
o Fluid filled lesions – cysts, abscess  
o Cholelithiasis 
3. Biopsy –  can be done in two forms  
ο Open biopsy is done during laparatomy and allows to take adequate tissue 
samples


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 341ο Needle biopsy is done percutaneously  
4. Cholangiography:  is contrast study of the biliary tree. The contrast can be given orally, 
percutaneously, intravenously, or by using endoscope; the last is known as 
Endoscopic Retrograde Cholangiopancreaticography (ERCP) 
  
References:  
2) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Approach to patients with Gastrointestinal diseases , pages 1725-1729.


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 3422.  Gastritis and peptic ulcer diseases  
 
Objectives: at the end of this unit the student will be able to:- 
1. Define gastritis and peptic ulcer diseases (PUD). 
2. List the etiologies of gastritis and PUD.    3. Describe the epidemiology of PUD. 
4. Explain the pathogenesis gastritis and PUD.    
5. Describe the clinical features of gastritis and PUD.    6. List the common complications gastritis and PUD. 7. Describe the most commonly used methods for the diagnosis of gastritis and 
PUD. 
8. Make an accurate diagnosis of gastritis and PUD.    9. Treat gastritis and PUD at the primary care level with appropriate drugs. 10. Refer those presenting with complications of gastritis and PUD to hospitals. 
 
2.1 Gastritis 
• Gastritis refers to histologically confirmed inflammation of the gastric mucosa. It 
is not synonymous with dyspepsia or gastric erythema seen during endoscopy. 
It is classified into:  
 
Acute gastritis   
• Commonly caused by: Helicobacter pylori .  
• Other causes include : 
o Drugs like ASA, NSAID ,  
o Alcohol in high doses,  
o Severe stress, and  
o Other infections such as viruses (CMV, Herpes simplex), mycobacterium, 
and syphilis.  
• Patients are usually asymptomatic but at times they may present with sudden 
onset of epigastric pain, with neutrophilic infiltration, edema and hyperemia of the 
gastric mucosa.


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 343• If not treated, H. pylori  gastritis may progress to one of the chronic gastritis. No 
specific treatment of acute gastritis is indicated. Removal of the offending agents 
may be adequate.  
Chronic gastritis 
• Defined as a histological demonstration of lymphocytic and plasma cell infiltration 
of gastric mucosa.  
• Course:  Superficial gastritis is followed by  atrophic gastritis (characterized by 
distortion and destruction of gastric glands) progressing to gastric atrophy (with 
loss of gastric glands), which then undergo intestinal metaplasia (replacement of 
gastric mucosal cells by intestinal epithe lial cells) and finally progressing to gastric 
carcinoma. 
Chronic gastritis is classified into two: 
• Type A gastritis  (chronic fundal gastritis)   
ο The inflammation is limited to gastric fundus and body with antral sparing.  
ο Associated with pernicious anemia, with circulating autoantibodies to 
parietal cells, which is why it is also known as autoimmune gastritis. 
• Type B- gastritis (chronic antral gastritis)   
ο It is more common than type gastritis.  
ο It commonly involves the antrum and mostly associated with H. pylori  
infection. However, the inflammation may progress to involve the gastric fundus and body causing pangastritis usually after 15 - 20 
years.   
ο Histology improves with eradication of H. pylori.  
 
Treatment of chronic gastritis : is aimed at controlling the sequellae, not the 
inflammatory process.


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years.   
ο Histology improves with eradication of H. pylori.  
 
Treatment of chronic gastritis : is aimed at controlling the sequellae, not the 
inflammatory process.  
• Lifelong parenteral Vitamin-B 12 is recommended for patients with pernicious 
anemia.  
• There is no need to treat H. pylori , unless there is ulcer or MALT Lymphoma.


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 3442.2 Peptic ulcer diseases 
 
Definition:  An ulcer is a break in the mucosal surface, bigger than 5mm in size with depth to 
sub- mucosa.  
• Peptic ulcer is caused by discrete tissue destruction caused by acid and pepsin.  
• Ulcers occur most commonly in the stomach (GU) and proximal duodenum (DU), 
and less commonly in the esophagus, and rarely on the other portions of small 
intestine. 
Incidence:   
• Duodenal ulcers occur more frequently than gastric ulcers. This is probably due to 
the likelihood of gastric ulcers being silent and presenting only after complications. 
Autopsy studies suggest similar incidence of gastric ulcers and duodenal ulcers.  
• Peptic ulcer disease occurs more commonly in males than females. 
• Gastric ulcers occur later in life than duodenal ulcers (peak is in the sixth decade).  
• About 90 -100% of duodenal ulcers and 75 - 85% of gastric ulcers are associated 
with H. pylori  infection.  
• About 15 - 20% of patients have both gastric and duodenal ulcers.  
• Patients with gastric ulcers have a 33% chance of developing subsequent duodenal 
ulcers. 
The most important risk factors are: 
1. Helicobacter pylori infection: 
• H. pylori  is a gram negative microaerophilic rod bacteria found attached to gastric 
epithelium, without invading the gastric epithelium.  
• The bacterium produces lots of factors, which enable its existence in the acidic 
environment that include:


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epithelium, without invading the gastric epithelium.  
• The bacterium produces lots of factors, which enable its existence in the acidic 
environment that include: 
ο Urease: which splits urea to CO 2 and ammonia, and  alkalinize the acidic 
environment  
ο Catalase, adhesins, lipase, platelet activating factor, etc. 
• The prevalence of H. pylori  infection varies throughout the world and depends to a 
great extent on the overall standard of living. 
• In developing countries 80% of the population may be infected by age 20. 
• Transmission of H. pylori  occurs from person to person following an oral-oral or 
fecal-oral route.


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 345Pathophysiology:  
•    H. pylori  infection is virtually associated with chronic active gastritis, but only 10 - 
15% of the infected individuals develop frank peptic ulcerations. The basis for this 
difference is unknown. The end results are dependent upon the interplay between bacterial and host factors.  
•  H. pylori  infection is present in 90 - 100% of duodenal ulcers and 75 - 85% of 
gastric ulcers. 
•   The end results of H. pylori  infection are:- 
ο Gastritis   
ο Mucosa associated lymphoid tissue  Lymphoma  (MALT lymphoma)  
ο peptic ulcer diseases    
ο Gastric cancer  
ο  
2. Non-steroidal anti inflammatory drugs  
• These are among the commonly used over-the-counter and prescription drugs. 
• The spectrum of morbidity ranges from nausea and dyspepsia (50 - 60%) to serious 
gastrointestinal complications, such as frank peptic ulceration complicated by perforations or bleeding in as many as 3 - 4% of users per year.  
• These drugs inhibit prostaglandin synthesis, which maintains gastro- duodenal 
mucosal integrity and repair.  
• Gastric ulcers occur at somewhat higher frequency than duodenal ulcers. 
3.  Miscellaneous factors  
• Cigarette smoking  - Higher incidence of peptic ulcer disease and complications in 
smokers, with delayed ulcer healing.  
• Generic factors , personality, and diet  may be associated with PUD; however the 
mechanisms are not yet established.


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smokers, with delayed ulcer healing.  
• Generic factors , personality, and diet  may be associated with PUD; however the 
mechanisms are not yet established.                 
• Corticosteroids alone do not predispose to ulcers; but they increase the risk of 
ulcer development if given with NSAIDS.  
 
Pathophysiology of Ulcer Diseases 
Peptic ulcers develop as a result of an imbalance between protective mucosal defensive 
factors and aggressive factors  
• Defensive factors include


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 346ο Prostaglandins,  
ο Mucus  
ο Bicarbonates  
ο Mucosal blood flow  
• Aggressive factors  
ο Pepsin 
ο Hydrochloric acid. 
Whereas acid-peptic injury is necessary for ulcer to develop, acid secretion is normal in 
almost all patients with gastric ulcers and increased in approximately a third of patients with duodenal ulcers. 
 
Clinical presentations  
• Manifestations are dependent on ulcer location and patient age.  
• Course is usually chronic and recurrent.  
• Pain is the most common symptom, and described as burning, gnawing or felt as 
hunger, often localized to epigastrium and relieved by food or antacids 
Gastric ulcer   
• Symptoms often do not follow a consistent pattern, especially when ulcer is located in 
pyloric channel, where symptoms of obstruction may predominate (bloating, nausea, vomiting due to edema and scarring). 
Duodenal ulcer  
• Pain tends to be consistent, usually absent when patient wakes up but appears in 
midmorning, and relieved by food but recurs again 2 - 3 hours after a meal.  
• Pain may be severe enough to awaken patient at night.


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 347Table V-2-1. Some differences in the clinical manifestations between DU and GU 
 
  Duodenal ulcer  Gastric ulcer  
Age Uncommon before age 
15 yrs  
 May develop in children as young as 5 
yrs, but peak incidence is later than DU.
 
Relation of pain to food/antacids
 Pain is relieved by food or antacids  
 Pain aggravated by ingestion of food
 
Relation of pain to food timing
 The pain characteristically comes 90 minutes to 3 
hr after ingestion of 
food (hunger pain)
 The pain comes within 30 minutes of ingestion of food 
 
 
Nausea and vomiting
 Not  common  
 Common  
 
Weight loss  Uncommon  Common because of 
fear to eat  
Perforation  more common  Less common  
Bleeding  Less common  more common  
Change in the character of pain may herald development of complications:  
• Duodenal ulcer pain that becomes const ant, is no longer relieved by food or 
antacids, or radiates to the back or to either upper quadrant, may signal penetration of 
the ulcer to the pancreas. 
• Duodenal ulcer pain accentuated rather than relieved by food, and/or 
accompanied by vomiting often indicates gastric outlet obstruction (G.O.O). 
• Abrupt, severe or generalized abdominal pain is characteristic of free ulcer 
perforation into the peritoneal cavity. 
Physical finding  
• Epigastric tenderness is most frequent finding.  
• Signs of peritonitis may be found in ulcer perforation. 
• Succussion splash is often detected in gastric outlet obstruction.


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 348Complications of PUD: All patients with the following complications need special care at 
referral hospitals 
• Haemorrhage   
o Is the most common complication of PUD, and patients present with 
hematemesis, passage of tarry stools, w eakness, hypotension, syncope, thirst 
and sweating resulting from associated blood loss.  
o Immediate treatment can be given via endoscopy (electrocautery, 
injection of alcohol/sclerosant etc.) or surgery. 
• Penetration (confined perforation)  
ο Is entering of adjacent confined space (e.g. lesser sac) or organ (e.g. 
pancreas, liver).  
ο Adhesions prevent leakage into peritoneal cavity.  
ο Radiographic evaluation with contrast study is usually needed to confirm the 
diagnosis.  
ο When medical therapy does not produce healing, surgery is recommended. 
• Free perforation   
ο Usually presents as acute abdomen with sudden, intense, steady epigastric pain. 
ο Diagnosis is confirmed with upright or lateral decubitus x-ray of abdomen.  
 
• Gastric outlet obstruction (GOO)  
ο May be caused by scarring, spasm, or inflammation.  
ο Symptoms include recurrent large volume vomiting, persistent bloating, fullness 
after eating, loss of appetite; weight loss, dehydration and alkalosis due to 
prolonged vomiting.  
ο Succussion splash for over 6 hrs after a meal, gastric aspiration or x - rays may 
help in the diagnosis.  
ο Treat such patients with nasogastric tube aspiration and acid suppression if


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prolonged vomiting.  
ο Succussion splash for over 6 hrs after a meal, gastric aspiration or x - rays may 
help in the diagnosis.  
ο Treat such patients with nasogastric tube aspiration and acid suppression if 
causes are temporary. But if the pyloric canal scarred, do endoscopic pyloric balloon dilatation or surgical relief of obstruction. 
• Stomach cancer  
ο Is intestinal type adenocarcinoma of  gastric body and antrum and commonly 
associated with H. pylori infection.


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 349ο Moreover, the incidence of MALT lymphoma (MALT=mucosa-associated 
lymphatic tissue) is increased in PUD.  
ο Treating H. pylori  might cure lymphoma, but chemotherapy or radical surgery 
must be used when such treatment fails to cure the tumour. 
ο For adenocarcinoma, surgery is always treatment of choice  
 
Diagnosis of PUD 1)  Barium examination of the upper gastrointestinal tract : sensitivity of this 
investigation to detect ulcers ranges from 70 – 90% 
2) Endoscopy : is most sensitive and specific method for the diagnosis of PUD. 
 Advantages  
a) Direct visualization and photographic documentation of the ulcer is possible.  b) Permits mucosal biopsy for detection of H. pylori infection.  c) Provides baseline reference for the assessment of ulcer healing. 
3) Tests for H. pylori  There are two categories of tests for the diagnosis of this bacterium: 
i) Invasive tests (endoscopy required) 
• Rapid urease test 
• Histology 
• Culture 
ii) Non invasive tests 
• Urea breath test - simple, rapid; useful for early follow up, false negative with 
recent therapy. 
• Serology – inexpensive, convenient, not useful for early follow-up 
Treatment  
Objectives of treatment:  
• Relief of symptoms (pain, dyspepsia) 
• Eradication of H. pylori  to prevent recurrence  
• Promote ulcer healing 
Medical treatment 
I. Treatment of H. pylori (see table VII-2-2)  
Indications: the following diseases with documented H. pylori infection


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• Eradication of H. pylori  to prevent recurrence  
• Promote ulcer healing 
Medical treatment 
I. Treatment of H. pylori (see table VII-2-2)  
Indications: the following diseases with documented H. pylori infection 
ο PUD                           
ο MALT lymphoma


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 350• No single agent is effective for eradication of H. pylori ; hence a combination of 
multiple drugs is essential. Proton pump inhibitors (omeprazole) are added to 
antibiotics or H 2 blockers (e.g.  Ranitidine) can be used alternatively.  
 Table V-2-2 Regimens recommended for eradication of H. pylori infection 
Triple therapy
 Dose   Duration  
Bismuth subsalicylate plus
 2 tabs QID  2 weeks  
Metronidazole plus  250 mg QID   
Tetracycline  500 mg QID   
   
Omeperazole plus  20 mg, BID  2 weeks  
Chlarithromycin plus 
  250 or 500mg BID   
Metronidazole or 
amoxicillin  500 mg BID/1 gm BID   
   
Quadruple therapy    
Omeperazole +  20 mg, BID  2 weeks  
Bismuth subsalicylate
 + 2 tabs QID   
Metronidazole +  250 mg QID   
Tetracycline  500 mg QID   
 
II.  Acid Neutralizing/Inhibitory Drugs  
A) Antacids  
• Are the most frequently used drugs before the advent of antihistamines (H 2 - 
blockers). They are now rarely, if ever, used as the primary therapeutic agent, 
however are often used by patients for symptomatic relief of dyspepsia.  
• A combination of magnesium hydroxi de and aluminum hydroxide (marketed as 
Maalox or other brands) are widely used at a dose of 15 -30 ml at 1 hour and 3 hours after each meal and at bedtime.


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 351B) H  2 receptor antagonists   
• Include cimetidine, famotidine, ranitidine and nizatidine.  
• Cimetidine is the most commonly used drug. The dose is 800 mg at bedtime or 
400mg twice a day for 4 - 6 weeks.  
• Ranitidine is used at a dose of 150 mg or ally twice a day or 300mg at bedtime for 
4 – 6 wks. 
C) Proton pump inhibitors   
• They inhibit the H+-pump, which is important for   synthesis of hydrochloric acid. 
• Omeperazole: 20mg orally daily for 4 - 8 weeks. 
• When these drugs are used for anti- H. pylori  treatment, it has direct antimicrobial 
effect on the organism. 
D) Dietary advice  
• There is no specific diet recommended for patients with peptic ulcer disease.  
• Patients are generally advised to avoid smoking, coffee, and foods that cause or 
aggravate their symptoms. 
Surgical treatment  is indicated for:  
• Perforation:  immediate surgery is recommended for acute perforation. If this is not 
possible, admit the patient to ICU and put on continuous nasogastric suction and 
broad-spectrum antibiotics. 
• Obstruction not responding to medical therapy 
• Uncontrolled/recurrent bleeding 
• Suspected malignancy 
• Symptoms refractory to medical management  
N.B.  For the types of surgical procedures and their complications, please refer Surgical 
textbooks.  
Dyspepsia   
• Is the classic symptom of PUD and is defined as pain centered in the upper 
abdomen or discomfort characterized by fullness, bloating, distension or nausea.


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textbooks.  
Dyspepsia   
• Is the classic symptom of PUD and is defined as pain centered in the upper 
abdomen or discomfort characterized by fullness, bloating, distension or nausea.  
• It’s a common clinical problem and may be seen in 25 - 40% of adults.  
• Only 15 - 25% patients with dyspepsia are found to have either gastric or duodenal 
ulcers. 
• Other causes include: 
ο Gastroesophageal reflux disease


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 352ο Gastric cancer 
ο Gastroparesis 
ο Gastritis 
• In up to 60% of dyspeptic patients no cause is identified ( Functional or non ulcer 
dyspepsia ) - a condition most likely related to an abnormal perception of events 
in the stomach caused by afferent visceral hypersensitivity. 
Non gastritis mucosal Injury  
1. NSAIDS  
• Acute ingestion: increases mucosal permeability and back diffusion    of H+ leading 
to hyperemia, sub epithelial hemorrhage and superficial erosions. 
• Chronic ingestion: inhibition of gastro duodenal mucosal prostaglandin synthesis 
leading to decreased mucus and bicarbonate production and mucosal blood flow 
finally resulting in frank ulceration may occur. 
2. Stress Related mucosal Damage 
• Mucosal ischemia caused by decreased blood flow (from shock, Catecholamine 
release) impairs mucosal resistance to acid back diffusion. Hyperemia of the 
mucosa evolves & erosions and then frank ulceration in the stomach and duodenum 
that go on to bleeding. 
Clinical features  
• May be absent  
• Epigastric pain  
• Hemorrhage (hematemesis, melena)  
Diagnosis  – History of drug ingestion  
• Endoscopy  
Treatment:   
• Removal of offending agent.  
• Antacids, H2-blokcer and surface acting agents (Sucralfate) are helpful. 
• In patients with hemorrhage – Volume replacement and endoscopic control of the 
bleeding.


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 353References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Peptic 
ulcer diseases and related disorders, pages 1746-1762. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Peptic ulcer diseases, pages 210-215.


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 3543. Malabsorption syndromes  
 
Learning Objectives: at the end of this chapter the student will be able to 
1. Define malabsorption syndromes 
2. List the etiologies of malabsorption syndromes 3. Explain the mechanisms of malabsorption syndromes 
4. Describe the clinical features of malabsorption syndromes    
5. List the common nutritional complications malabsorption syndromes. 6. Make a diagnosis of malabsorption syndrome   7. Refer the patient to hospitals for better diagnosis and treatment 
 
Definition:  Syndromes resulting from impaired absorption of one or more dietary nutrients 
from the small bowel.  
• Many diseases or their consequences can cause malabsorption.  
• The mechanism may be direct impairment of absorption or abnormalities of digestion 
that finally leads to impaired absorption.  
• Malabsorption may occur for specific nutrients such as carbohydrates, fats, or 
micronutrients or may affect many nutrients at the same time. 
Etiologies  
1) Maldigestion: refers to a defect either in the intraluminla hydrolysis of triglycerides, or in 
micelle formation , which results from the following conditions  
a) Pancreatic insufficiency  due to chronic pancreatitis  , pancreatic carcinoma  
b) Deficiency of conjugated bile salts  due to cholestatic or obstructive liver diseases  
c) Bile salt deconjugation due to bacterial overgrowth in blind loop ( after Billroth-II 
gastrectomy ) or jejuna diverticulitis


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b) Deficiency of conjugated bile salts  due to cholestatic or obstructive liver diseases  
c) Bile salt deconjugation due to bacterial overgrowth in blind loop ( after Billroth-II 
gastrectomy ) or jejuna diverticulitis  
d) Inadequate mixing of gastric contents  with bile salts and pancreatic enzymes as 
a result of previous  gastric surgery 
2) Intrinsic bowl diseases  ( damage to the absorptive surface of the intestine ) 
a) Celiac disease  causing flattening of the intestinal villa and inflammatory cell 
infiltration. 
b) Whipple’s diseases:  is a systemic disease that may cause intestinal mucosal 
damage and lymphatic obstruction.


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 355c) Collagenous sprue : deposition of collagen substance in the lamina propia of the 
intestine  
d) Non granulomatous ulcerative ileojejunitis a rare condition of unknown etiology 
characterized by fever, weight loss and features of absorption. 
e) Eosinophilic gastroenteritis:  characterized by peripheral eosipnophilia, and 
infiltration of the wall of the stomach, small intestine or colon by eosinophils. Many 
patients present with specific food allergy.  
f) Amylodosis :  amyloid infiltration of the submucosa of the small intestine  
g) Crohn’s diseases :  an inflammatory bowel diseases which may cause mucosal 
damage  
3) Inadequate absorptive surface:  from extensive small bowel resection. Resection of 50 
% of small intestine is well tolerated, if the remaining bowel is normal.  
4) Lymphatic obstruction  
a) Intestinal lymphangiectasia  
b) Intestinal lymphoma 
5) Multiple defects  
a) After gastrectomy : which may result in poor mixing of gastric contents with 
pancreatic enzymes and stasis in the afferent loops with bacterial overgrowth ( as in Billroth II gastrectomy) can cause malabsorption. 
b) Radiation enteritis : interferes with the blood supply of the intestine. Bacterial 
overgrowth may occur secondary to radiation stricture , lymphatic obstruction may 
occur due to edema or fibrosis  
c) Diabetes mellitus : alter gut motility from diabetic neuropathy, bacterial overgrowth


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overgrowth may occur secondary to radiation stricture , lymphatic obstruction may 
occur due to edema or fibrosis  
c) Diabetes mellitus : alter gut motility from diabetic neuropathy, bacterial overgrowth 
and exocrine pancreatic insufficiency may lead to malabsorption. 
6) Other causes 
a) Infections :  viral , bacterial or parasitic in fections may cause malabsorption  
i) In HIV infected patients  malabsorption may be caused by Cryptosporidiosis , 
Isosporiosis or intestinal mucosal atrophy due to HIV virus itself (HIV  
enteropathy ) 
ii) Tropical sprue:  endemic malabsorption disorder occurring in the tropics. It is 
believed to have an infectious cause. 
iii) Parasitic cause of malabsorption : include Hookworm, tapeworm and 
strolgyloidiasis.


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 356b) Hypoparathyroidism 
c) Drugs:  neomycin, kanamycine may cause malabsorption.  Phenytoin causes a 
selective folic acid malabsorption      
 
Clinical features  
Signs and symptoms 
• Symptoms of malabsorption are caused either by the effects of osmotically active 
substances within the gastrointestinal tract or the resulting nutritional deficiencies.  
• Patients may present with some or all of the following clinical manifestations. 
General symptoms:   
• Steatorrhea: passage of abnormal stools, which are greasy soft , bulky , and foul 
smelling  and may float in the toilet because of their increased gas content : a film of 
greasy or oil droplets may be seen on the surface of the water . This is often associated with abdominal distension, bloating, or discomfort and flatulence resulting 
from increased intestinal bulk and gas production 
• Weight loss:  which may be severe and involve marked muscle wasting. 
 Secondary nutritional deficiencies:   
• Deficiency of iron, folic acid, or B12  leading to anaemia 
• Calcium deficiency (common) partly due to  lack of vitamin D causing rickets, 
osteomalacia ,  paresthesia , tetany and carpopedal spasms. 
• Thiamine (vitamin B
1) and B 12 deficiency may cause neuropathy, 
• Malabsorption of vitamin K (mainly fat-soluble) can lead to hypoprothrombinemia 
with bruising and a bleeding tendency.  
• Severe riboflavin (vitamin B 2) deficiency may cause a sore tongue and angular 
stomatitis,


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• Malabsorption of vitamin K (mainly fat-soluble) can lead to hypoprothrombinemia 
with bruising and a bleeding tendency.  
• Severe riboflavin (vitamin B 2) deficiency may cause a sore tongue and angular 
stomatitis,  
• Vitamin A, C, and niacin deficiencies seldom cause clinical problems. 
• Protein malabsorption may lead to hypoproteinemic edema, usually of the lower 
limbs.  
• Dehydration, potassium loss, and muscle weakness can follow profuse diarrhoea.  
• Secondary endocrine deficiencies may result from malnutrition.


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 357Some causes of malabsorption may have distinct clinical features:  
• Lactase deficiency  manifests with  explosive diarrhoea, abdominal bloating and gas 
after milk ingestion 
• Pancreatic lipase deficiency: greasy stools with undigested dietary fat (triglycerides) 
• Dermatitis herpetiformis is often associated with a mild degree of celiac-like 
enteropathy 
• Biliary cirrhosis and pancreatic cancer may cause jaundice 
• Mesenteric ischemia may cause abdominal angina 
• Chronic pancreatitis may cause boring central abdominal pain 
• Patients with Zollinger-Ellison syndrome frequently manifest with severe  persistent 
ulcerative dyspepsia.  
Diagnostic workup 
• Symptoms and signs may point to the diagnostic impression of malabsorption.  
• Any combination of weight loss, diarrhoea, and anaemia should raise the suspicion of 
malabsorption.  
• However, laboratory studies are essential to confirm the diagnosis 
Common laboratory tests: 
1) Direct measurement of faecal fat:  3 - 4 days stool collection is required for this 
measurement. Faecal fat over 6 g/day is abnormal.   
2) Stool inspection, microscopic examination: look for undigested food fragments, 
and do direct microscopy for ova and parasites, and Sudan III staining for the 
presence of grease/fat in the stool. 
3) Absorption tests help to define the site of the lesion; D-xylose absorption test is specific for proximal small-bowel (jejunal) absorption. Five grams of D-


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presence of grease/fat in the stool. 
3) Absorption tests help to define the site of the lesion; D-xylose absorption test is specific for proximal small-bowel (jejunal) absorption. Five grams of D-
Xylose is given orally to the fasting pat ient, and urine is collected for the next 5 
hours. Smaller than 1.2 grams of D-xylose in the 5-hours urine collection is considered abnormal. 
4) Iron malabsorption: low serum ferritin and serum iron levels with adequate diet 
and lack of blood loss indicates iron malabsorption. Diminished iron storage on bone marrow examination may also be found. 
5) Folic acid absorption:  is suggested by low serum or RBC folate level with 
adequate diet and little alcohol intake. 
6) Schilling test is used to diagnose Vit B-12 malabsorption.


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Internal Medicine 
 
 3587) Abdominal X-rays:  upper GI series with small-bowel follow-through may be helpful. 
Plain abdominal x-ray may show pancreatic calcification as a sign of chronic 
pancreatitis. 
8) Small-bowel biopsy  can be taken during endoscopy to show mucosal changes. 
Treatment   
• Is individualised according to underlying disease.   
• However, if the underlying cause is not treatable as in short bowel syndrome, 
adequate substitution of missing nutrients must be ensured and diet adjusted appropriately. 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition,  
Disorders of absorption , pages 1763-1775.


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Internal Medicine 
 
 3594. Pancreatic diseases 
 
Learning objectives: at the end of this unit the student will be able to 
1. Define acute and chronic pancreatitis 
2. List the etiologies of acute and chronic pancreatitis 3. Explain the mechanisms of acute and chronic pancreatitis  
4. Describe the clinical features of acute and chronic pancreatitis 
5. List the common complications acute and chronic pancreatitis  6. Make a diagnosis of acute and chronic pancreatitis &  7. Refer patients to hospitals for better diagnosis and treatment 
 
4.1. Acute Pancreatitis 
Etiology:  
1) Biliary tract disease especially stones 
2) Alcoholism 
3) Drugs (furosemide, valproic acid, azathioprine, sulfasalazine) 4) Infection (e.g. mumps) 5) Hypertriglyceridemia 
6) Structural abnormalities of pancreatic duct (stricture, cancer, pancreas divisum) 
7) Abnormalities of common bile duct and ampullary region 8) Surgery of stomach, biliary tract 9) Vascular disease 10) Trauma 
11) Hyperparathyroidism, hypercalcemia 
 
Signs and symptoms: 
• Fever 
• Severe abdominal pain radiating to the back; sudden in biliary pancreatitis, 
developing over weeks in alcoholism. Pain is steady, boring, persistent, 
relieved by leaning forward, and accentuated by coughing, movement and deep breathing. 
• Abdominal tenderness with muscular rigidity, and sometimes board like 
abdomen


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Internal Medicine 
 
 360• Hypoactive bowel sounds 
• Nausea, vomiting 
• Tachycardia, tachypnia 
• Jaundice may be present 
• Lung examination may reveal lim ited diaphragmatic excursions and 
evidence of atelectasis 
 
Complications: 
• Early death may be due to cardiovascular instability or respiratory failure; later death due 
to pancreatic or pseudocyst infection. 
• Pancreatic infection of devitalized retroperitoneal tissue with sepsis 
• Pancreatic pseudocyst may be secondarily infected, bleed or rupture 
Diagnosis: 
• Increased serum amylase, lipase  
• WBC : usually between 12,000 to 20,000/mm3 
• Hematocrit  may be as high as 50-55 % due to third-space losses. 
• Hyperglycaemia  
• Serum calcium  is decreased 
• Bilirubin  may be increased 
• X-rays of the abdomen (Supine and upright plain x-rays); Chest x-ray  
• Ultrasound of the abdomen (if available CT)  
Differential diagnosis:   the following diseases can mimic acute pancreatitis  
♦ Perforated gastric or duodenal ulcer 
♦ Mesenteric infarction 
♦ Strangulating intestinal obstruction 
♦ Ectopic pregnancy 
♦ Dissecting aneurysm 
♦ Biliary colic 
♦ Appendicitis 
♦ Diverticulitis 
♦ Inferior wall myocardial infarction 
♦ Haematoma of abdominal muscles or spleen.


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Internal Medicine 
 
 361Prognosis 
Ranson's 11 prognostic signs  help estimate the prognosis of acute pancreatitis.  
• Five signs can be documented at admission:  
ο Age more than 55 yr 
ο Serum glucose over 200 mg/dl (> 11.1 mmol/L),  
ο Serum LDH over 350 IU/L  
ο AST over 250 units/L and  
ο WBC count over 16,000/µL.  
• The development of the following within 48 h after admission indicates worsening 
prognosis:  
ο Hct drop by more than 10% 
ο BUN rise greater than 5 mg/dl (> 1.8 mmol Urea/L) 
ο Serum Ca less than 8 mg/dl (< 2 mmol/L) 
ο Arterial Po 2  less than 60 mm Hg 
ο Base deficit over 4 meq/l 
ο Estimated fluid sequestration more than 6 L 
• Mortality increases with the number of positive signs:  
ο If fewer than three signs are positive, the mortality rate is less than 5%;  
ο If three or four signs are positive, mortality is between 15 to 20%. 
ο The presence of 7 – 8 of these criteria is associated with 100% mortality.  
• Acute pancreatitis associated with necrosis and haemorrhage has a mortality rate of 
about 10 to 50%. This diagnosis is suggested by  
ο A progressive decrease in Hct,  
ο The presence of hemorrhagic fluid within ascites,  
ο The reduction of serum Ca++ level,  
ο The presence of Grey Turner's  and/or Cullen's sign  (indicating extravasations of 
hemorrhagic exudates to the flanks or umbilical region, respectively). 
Treatment 
Mild oedematous pancreatitis:


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ο The reduction of serum Ca++ level,  
ο The presence of Grey Turner's  and/or Cullen's sign  (indicating extravasations of 
hemorrhagic exudates to the flanks or umbilical region, respectively). 
Treatment 
Mild oedematous pancreatitis:   
• Keep patient NPO (nothing per os) until manifestations of acute inflammation subside 
• Give sufficient intravenous fluids 
• Insert nasogastric tube.


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Internal Medicine 
 
 362Severe acute pancreatitis:   
• Refer to hospitals for admission to intensive care unit 
• Vital signs and urine output are monitored at least every 1 hr 
• Accurate metabolic flow sheet which should be checked every 8 hrs. 
• Arterial blood gases are determined as necessary 
• Hct, glucose, electrolytes (Ca, Mg), CBC, platelet count, coagulation parameters, 
total protein with albumin, BUN, creatinine, amylase, and lipase studies performed 
daily. 
• Keep patient NPO with NG tube insertion  
• Give H 2 receptor blockers IV 
• Fluids may be given up to 6 - 8 L/d.  
• Give oxygen as needed 
• Severe pain should be treated with Pethidine 50 to 100 mg IM every 4 to 6 hrs and 
as needed in patients with normal renal function (morphine causes the sphincter of 
Oddi to contract and should be avoided).  
• Treat hyperglycaemia if over 250 mg/dl.  
• If symptoms of calcium depletion appear give calcium gluconate 10 - 20 ml IV in 1 
liter of replacement fluid. 
Surgery  is indicated for  
• Trauma 
• Uncontrolled biliary sepsis 
• Inability to distinguish acute pancreatitis from other causes of acute abdomen 
• To drain a pseudocyst that is expanding rapidly, secondarily infected, or associated 
with bleeding or impending rupture. 
 
4.2. Chronic pancreatitis 
Etiology: 
• Alcoholism : 70 -80% of chronic pancreatitis is associated with alcoholism 
• Idiopathic 
• Hereditary 
• Microlithiasis 
• Hyperparathyroidism


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with bleeding or impending rupture. 
 
4.2. Chronic pancreatitis 
Etiology: 
• Alcoholism : 70 -80% of chronic pancreatitis is associated with alcoholism 
• Idiopathic 
• Hereditary 
• Microlithiasis 
• Hyperparathyroidism 
• Obstruction of the main pancreatic duct due to stenosis, stones, or cancer


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Internal Medicine 
 
 363Signs and symptoms :  
• Persistent or recurrent epigastric or left upper abdominal pain, nausea, vomiting, 
anorexia, constipation, flatulence and weight loss are common.  
• In advanced disease, patients may develop steatorrhea, recurrent acute attacks of 
pain which become more constant later and insulin secretion is diminished with 
impaired glucose tolerance. 
Diagnosis:  
• Laboratory tests are frequently normal, but inflammation markers may be 
minimally elevated. 
• Plain abdominal x-ray may demonstrate  pancreatic calcification in 30% of cases 
• Abdominal ultrasound or CT to detect calcifications, dilated ducts and atrophic 
gland 
• ERCP is most sensitive test and may show dilated ducts, intraductal stones, 
strictures or pseudocyst 
• Tests of pancreatic function:  assess endocrine and exocrine function, including 
glucose tolerance test (see chapter on diabetes mellitus). For exocrine function do ecretin test. 
• Stool tests:  faecal chymotrypsin 
Treatment  
• Alcohol intake should be avoided.  
• At times, IV fluids and fasting prove beneficial.  
• Use of oral pancreatic enzymes (30.000 U of lipase) with each meal may improve 
symptoms.  
• If steatorrhea is particularly severe and refractory, medium chain triglycerides, 
which are absorbed without pancreatic enzymes, can be provided as an alternative source of fat.   
• Supplementation with fat-soluble vitamins (A, D, K) is sometimes required.


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which are absorbed without pancreatic enzymes, can be provided as an alternative source of fat.   
• Supplementation with fat-soluble vitamins (A, D, K) is sometimes required.  
• Relapse may require treatment similar to that of acute pancreatitis.  
• A pancreatic pseudocyst, which causes chronic pain, needs referral to centres with 
surgical facilities and expertise, where it can be decompressed into a nearby 
structure to which it firmly adheres (e.g., the stomach) or into a defunctionalized loop of jejunum.


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Internal Medicine 
 
 364• Diabetes mellitus rarely occurs in chronic pancreatitis. For most patients, serum 
glucose level of 200 to 250 mg is acceptable and doesn’t require treatment. It is 
better to maintain the patient in a slightly hyperglycaemic range than run a risk hypoglycaemia caused by overzeal ous administration of insulin. 
• Patients with chronic pancreatitis are at increased risk for pancreatic cancer. 
Worsening of symptoms, especially with devel opment of a pancreatic duct stricture, 
should prompt an examination for malignancy.  
  
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Acute 
and chronic pancreatitis, 1895-1906. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Diseases of the pancreas, pages 240-244.


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Internal Medicine 
 
 3655. Hepatitis 
 
Learning objectives: at the end of this unit the student will be able to 
1. Define acute and chronic hepatitis 
2. List the etiologies of acute and chronic hepatitis  3. Explain the routes of transmission of the different hepatitis viruses 
4. Describe the clinical features of acute and chronic hepatitis  
5. List the common complications acute and chronic hepatitis 6. Identify the antigens and antibodies used for the diagnosis of viral hepatitis 7. Make a diagnosis of acute and chronic hepatitis &  8. Refer patients to hospitals for better diagnosis and treatment 
 
• Hepatitis is a broad category of clinico-pathologic conditions resulting from viral, toxic, 
pharmacologic or immune mediated damage to the liver.  
• Hepatocellular necrosis and inflammatory cell infiltration of the liver are common 
pathologic features.  
• There are two types of hepatitis, which are defined based on duration: 
I. Acute hepatitis:  lasts for about 6 months or less. 
II. Chronic hepatitis:  sustained inflammatory response for over 6 months. 
 
    5.1 Acute hepatitis  
Etiologies:   
1) Viruses are the commonest causes, and include hepatitis A, B, C, D, E, G, viruses and 
other viruses such as EBV, CMV etc. 
2) Toxins (amanita phylloides in mushroom poisoning; carbon tetrachloride). 
3) Drugs:  acetaminophen, INH, halothane, chlorpromazine, erythromycin, heavy alcohol 
intake 
4) Others  
a. Wilson’s disease 
b. Herbs


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Internal Medicine 
 
 3665.1.1 Acute viral Hepatitis  
• Is the most common form of acute hepatitis; Caused by hepatitis viruses (designated as 
HV) HAV, HBV, HCV, HDV, HEV, HGV (Non A. Non B virus), all of which are RNA 
viruses except HBV, which is a DNA virus. 
• HDV is an incomplete RNA virus and requires the presence of HBV to cause infection. 
Thus, it causes hepatitis when HDV infection occurs at the same time  as HBV infection (HDV co-infection) or in patients with chronic hepatitis B infection (super infection). 
• The complete HBV (Dane particle) consists of several antigenetically distinct 
components, including a surface coat (hepatitis B surface antigen [HBsAg]) and a core of circular DNA, DNA polymerase, hepatitis B core antigen (HBc Ag), and hepatitis B 
envelope antigen (HBe Ag).  
 
  
  
 
    
 
Transmission  
• In HAV and HEV transmission is feacooral. Both viruses are implicated in most 
instances of water borne and food transmitted infection, and in epidemics of viral 
hepatitis. 
• HBV is mainly transmitted by parentera l (via blood and blood products, contaminated 
needles), sexual contacts and perinatal route. The virus is found in all body fluids and excreta.  
•  Like HBV, HCV is largely transmitted parenterally. It is the main cause of post 
transfusion hepatitis, especially before the discovery of anti HCV antibodies. The virus is transmitted less frequently through the sexual and perinatal routes.  
 
Clinical and laboratory manifestations


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transfusion hepatitis, especially before the discovery of anti HCV antibodies. The virus is transmitted less frequently through the sexual and perinatal routes.  
 
Clinical and laboratory manifestations  
• The prodromal phase  lasts for several days and characterized by malaise, fatigue, 
anorexia, nausea, vomiting, myalgia and headache.  Patients will have aversion to smell 
of food and cigarette with mild fever and flue like symptoms.  Surface antigen (HBsAg) 
Core antigen (HBc Ag) 
DNA polymerase  HBV DNA


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Internal Medicine 
 
 367• Arthritis and urticaria may be present particularly in HBV which are attributed to 
immune complex deposition.  
• Jaundice appears late , usually when the patients start to improve in their sense of  
well being. It may be absent (Nonicteric hepatitis) in some patients.  
• Dark urine and pale stool is common in cholestasis  
• The liver is usually tender and enlarged, and splenomegaly occurs in 20% of the 
cases.  
Laboratory   
1) Liver enzymes:  Damage to hepatocytes causes release of intracellular enzymes like 
alanine transaminase (ALT), and aspartate transaminase (AST). Normal levels range 
between 0 and 35 U/L.  In acute hepatitis, they often rise to 20 fold or more.   
2) Serum bilirubin:  normal levels range between 0.3 and 1 mg/dl. when  levels go above 
2.5 -3.0 mg/dl jaundice appears (called icteric hepatitis)    
3) Alkaline phosphatase  may be increased by about 3 fold except in cholestatic hepatitis, 
in which the increment is very much higher.  
4) CBC: leucopenia with atypical lymphocytes (relative lymphocytosis) is common. 
5) Serodiagnosis: serodiagnosis involves antigen/antibody detection.  
• It allows the identification of etiologic agents  
• It helps in planning of preventive and other public health measures for close 
contacts of infected people  
• It helps in evaluating the prognosis.  
a) Diagnosis of HAV  can be made by detection of anti HAV antibody, which is IgM


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• It helps in planning of preventive and other public health measures for close 
contacts of infected people  
• It helps in evaluating the prognosis.  
a) Diagnosis of HAV  can be made by detection of anti HAV antibody, which is IgM 
initially and IgG later on. The IgG antibody confers lifelong immunity.  
b) Diagnosis of HBV infection  The following antigens and antibodies can be 
detected to HBV infection  and help in diagnosis , monitor disease progress , 
infectivity, and predict the prognosis: 
i)  Antigens  
(1) HBsAg   : 
• Usually cleared within 3 months. It may persist in some patients for 6 
months to one year without complications.   
• Its clearance from the blood precedes the appearance of anti-HBs antibody 
with a time gap in between (known as the window period), during which the 
only evidence of HBV infection may be anti-HBc antibody.


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Internal Medicine 
 
 368(2) HBeAg   indicates HBV replication and high chance of infectivity to others 
ii) Antibodies  
(1) Anti HBs antibody  – confers long term immunity  
(2) Anti HBc   - IgM  indicates recent infection , IgG indicates remote infection  
(3) Anti HBe : active infection 
N.B. Anti-HBc and Anti-HBe do not provide immunity.  
c) HDV can be diagnosed by detection of anti HDV antibody.  
d) HCV is diagnosed by detecting anti HCV antibody.  
 
Table V -5-1. Comparisons of   some features of hepatitis A, B, and C  
Feature  Hepatitis A  Hepatitis B  Hepatitis C
Incubation  15 to 45 days 
(mean 30)  30 to 180 days (mean 60 to 90)
 15 to 160 days (mean 
50)
 
Onset  Acute  Often insidious  Insidious  
Age preference
 Children, young adults
 Any age  Any age but 
more 
common in 
adults  
Transmission Route  
Fecal-oral  + + +  - Unknown  
Other non-
percutaneous 
routes  ± + + + + 
Percutaneous  ± + + +  + + +  
Other Characteristics  
Severity  Mild Often severe  Variable  
Prognosis  Generally good  Worse with age, debility
 Moderate


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 369Progression 
to chronicity  None  Occasional (5% to 10%)
 Frequent (65% -85%)
 
Prophylaxis  Immunoglobulin /hepatitis A vaccineStandard IG (not documented), HBIG, HB vaccine
 None  
Carrier  None  0.1% to 30%  Exists but prevalence unknown
 
 
Complications   
1)  Cholestatic hepatitis  –  
• Occurs most commonly during HAV and HEV infection  
• Self limited  
• Pruritus is a common symptom  
• Marked conjugated hyperbilirubinemia presenting with dark urine and pale stool  
• Increased alkaline phosphatase  
2) Fulminant hepatitis  : in about 1% of cases  
• Is defined as the onset of encephalopathy occurring within 8wks in a patient with 
acute liver disease 
• Associated with massive hepatocellular necrosis  
• Commonly follows  HAV, HBV (usually super infection of HBV infection by HDV), 
HCV and HEV (in pregnancy) 
3) Chronic hepatitis  
• Occurs in HBV and HCV infection  
• Manifest with persistently increased AST and ALT for over 6 months,  
• Slowly resolving HBV infection  may persist for 6-12 m with eventual complete 
resolution  
• Persistent HBV infection  (persistence of HBsAg) without evidence of liver 
damage resulting in asymptomatic or “healthy” HBV carriers.


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Internal Medicine 
 
 370Management  
• Mainly supportive  
ο Rest to limit fatigue  
ο Maintain hydration 
ο Adequate dietary intake   
• Vitamin supplementation has no proven value but vitamin K can be given if there is 
prolonged cholestasis. 
• Alcohol should be avoided until serum transaminases normalize  
• Metochlopromide (plasil) – for nausea 
• Admission 
ο  Patients with severe nausea and vomiting. 
ο  Patients with deteriorating liver function, especially those with 
encephalopathy or prolonged prothrombin time. 
• In general HAV may be regarded as non-infectious after 2 - 3 wks. HBV is potentially 
infectious to contacts throughout its course, although the risk is low once HBS 
antigen has cleared.   
• Interferon treatment is effective for HCV infection 
 
Prevention  
Prevention of HAV and HEV 
• General hygienic measures – Hand washing after toilet use; careful handing, 
disposal and sterilization of excret a and contaminated clothing and utensils. 
• For close contacts of HAV infected people  
ο Immune serum globulin (IgG) as soon as possible but no later than 6 wks after 
exposure 
ο Active immunization  
Prevention of HBV infection 
• Meticulous disposal of contaminated needles and other blood contaminated utensils  
• For close contacts of HBV infected patients, give HBIG within 7 days and 
subsequently HBV vaccine ( ∼ HBsAg) 
• Dose   of HBV vaccine 
ο 2.5μg for < 11 yr (when mother is HBsAg - Ve)


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• For close contacts of HBV infected patients, give HBIG within 7 days and 
subsequently HBV vaccine ( ∼ HBsAg) 
• Dose   of HBV vaccine 
ο 2.5μg for < 11 yr (when mother is HBsAg - Ve) 
o 5 μg for 11 – 19 yr & children < 11 yr born to HBsAg positive mother


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Internal Medicine 
 
 371o 10μg for immunocompetent adult. 
 
5.1.2 Alcoholic Fatty liver and Hepatitis 
Alcohol abuse is the most common cause of liver disease in the western world. Three major 
pathologic lesions resulting from alcohol abuse and appearing as stages/spectrum of the disease:  
1. Fatty liver 2. Alcoholic hepatitis  3. Cirrhosis  
The first two are potentially reversible, but the last one is not.  
1. Alcoholic fatty liver : is characterized by 
 Right upper quadrant pain  
 Incidentally discovered tender hepatomegally 
 Jaundice is rare, transaminases are mildly elevated (< 5X normal). 
 Completely reversible on cessation of alcohol  
2. Alcoholic Hepatitis : is severe and prognostically ominous lesion and 
characterized by the following pathologic triads:  
• Mallory bodies (intracellular eosinophilic aggregates  of cytokeratins), 
usually seen near or around nuclei  
• Infiltration by polymorphnuclear leukocytes  
• A network of interlobular connective tissues surrounding hepatocytes and 
central veins (spider fibrosis) 
Clinical manifestations of alcoholic hepatitis:  include 
• Weight loss, anorexia, nausea, vomiting and abdominal pain are common 
presenting symptoms. 
• Hepatomegally is found in 80% and splenomegaly is often present  
• Fever 
• Jaundice, spider angioma, palmar erythema, gyneacomastia and loss of 
body hair. 
• Ascites and encephalopathy may be present and indicate severe disease.


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• Hepatomegally is found in 80% and splenomegaly is often present  
• Fever 
• Jaundice, spider angioma, palmar erythema, gyneacomastia and loss of 
body hair. 
• Ascites and encephalopathy may be present and indicate severe disease.  
• CBC strikingly elevated. Transaminases modestly increased (200 – 400 
IU/l).


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Internal Medicine 
 
 372• The ratio of ASAT to ALAT frequently exceeds one in contrast to viral 
hepatitis in which the ratio is approximately one.  
• Prolonged prothrombin time, hypoalbum inemia and hyperglobulinemia may 
be found. 
Complications and prognosis  
• Alcoholic Hepatitis can reverse with cessation of alcohol, but more 
commonly progresses to cirrhosis.               
 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Acute 
hepatitis, pages 1822-1842. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Diseases of the liver, pages 249-264.


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Internal Medicine 
 
 3736. Chronic Liver Diseases 
 
Learning objectives: at the end of this unit the student will be able to 
1. Define chronic liver diseases 
2. List the etiologies of chronic liver diseases 3. Describe the clinical features of chronic liver diseases 
4. List the common complications of chronic liver diseases 
5. Make a presumptive diagnosis of chronic liver diseases 6. Refer patients to hospitals for better diagnosis and treatment 
Chronic liver diseases include:  
A. Chronic hepatitis 
B. Liver cirrhosis 
C. Hepatocellular carcinoma (Hepatoma) 
 
A. Chronic hepatitis   
Definition: Chronic hepatitis is d efined as a hepatic inflammatory process that fails to resolve 
after 6 months.  
Etiologies: 
1) Except HAV and HEV, all hepatitis viruses can cause chronic hepatitis 2) Other causes             
a) Drugs like methyldopa b) Autoimmune disorders  c) Idiopathic causes  
Pathological classification  
1. Chronic persistent hepatitis  - inflammatory activity is confined to portal areas. 
2. Chronic lobular hepatitis   
ο Inflammatory activity and necrosis are scattered throughout the lobule.  
ο Limiting plates of periportal hepatocytes are intact and no periportal fibrosis. 
3. Chronic active hepatitis :  
ο Inflammatory activity in portal areas spills out into the lobule (periportal 
hepatitis, piecemeal necrosis) in association with necrosis and fibrosis.   
ο Thought to have a significant risk for progression to cirrhosis and hepatic 
failure.


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Internal Medicine 
 
 374Chronic viral hepatitis  
• Complicates about 1% of acute hepatitis B (young, immunocompetent) and 85-90% 
of acute hepatitis C will develop chronic hepatitis. About 20% of the later will develop 
cirrhosis in 10-20yrs. 
• Subjects with either HBV or HCV infection have greater risk of developing 
hepatocellular carcinoma       
Treatment  can suppress hepatic inflammatory activity in 30-40% 
•  Hepatitis B - therapy is indicated for patients positive for HBsAg and HBcAg (High 
replicative phase). Treat with interferon α and Lamivudine.  
•  Hepatitis C can be treated with interferon α and ribavirin 
              
B.   Cirrhosis of the liver and its complications 
• It is the end result of fibrous scarring and hepatocellular regeneration, that constitute 
the major responses of the liver, to a variety of long standing inflammatory, toxic, metabolic and congestive insults. 
• The normal hepatic lobular architecture is replaced by interconnecting bands of fibrous 
tissue surrounding nodules derived from foci of regenerating hepatocytes.   
• The following pathologic changes are the cause of the clinical manifestations and  
complications of cirrhosis 
1) Fibrous scarring and disruption of hepatic architecture distort vascular bed leading to                 
Portal hypertension and intrahepatic shunting 
2) Disturbed hepatocellular function  
 Clinical and laboratory features resulting from Hepatocellular dysfunction  
• Hypoalbuminemia


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Portal hypertension and intrahepatic shunting 
2) Disturbed hepatocellular function  
 Clinical and laboratory features resulting from Hepatocellular dysfunction  
• Hypoalbuminemia  
• Decreased coagulation factors resulting in prolonged prothrombin time 
• Hyperbilirubinemia 
• Increased  blood ammonia level  
• Hepatic encephalopathy 
• Ascites 
 Portal HTN  
• Ascites.


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Internal Medicine 
 
 375• Varices 
• Splenomegaly causing thrombocytopenia and leucopenia. 
• Hepatic encephalopathy 
Major causes of Cirrhosis 
1) Alcohol and HCV are major causes in western world  
2) HBV is the commonest cause in developing countries  3) Other causes include: 
o Biliary obstruction (Intrahepatic and extrahepatic) leading to Biliary cirrhosis 
o Autoimmune hepatitis. 
Major complications of cirrhosis 
1) Portal Hypertension (HPN)  
• Normal portal pressure gradient 10 -15cm of saline  
• Portal hypertension is said to exist when the portal pressure gradient is over 30 cm of 
saline  
• Portal hypertension leads to the formation of venous collateral vessels between the 
portal and systemic circulation. Collateral vessels may form at several sites, the most important clinically being those connecting the portal vein to the azygous vein that form dilated, tortuous veins (varices) in the submucosa of the gastric fundus and 
esophagus. 
Types of portal hypertension 
i. Presinusoidal portal HPN  – increased resistance to portal blood flow into the liver  
E.g.  Schistosomiasis causes periportal fibrosis and presinusoidal portal HPN 
ii. Sinusoidal portal HPN  – is the commonest and found in cirrhosis. The resistance is 
in the sinusoids of the liver. 
iii. Post sinusoidal portal HPN  – increased resistance to hepatic venous outflow from 
the liver and causes include hepatic vein thrombosis and congestive heart failure.  
2) Variceal hemorrhage


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in the sinusoids of the liver. 
iii. Post sinusoidal portal HPN  – increased resistance to hepatic venous outflow from 
the liver and causes include hepatic vein thrombosis and congestive heart failure.  
2) Variceal hemorrhage  
• Esophageal varices – has a mortality of 30-60% if it bleeds 
• May present with hematemesis, melena, hematochezia  
Treatment of Variceal hemorrhage  depends on the speed and volume of bleeding.  
• Acutely bleeding patients should be referred to hospitals for intensive care. 
• Resuscitation


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Internal Medicine 
 
 376Medical Therapy  
• Somatostatin (or octreotide)  reduces splanchnic blood pressure when given 
intravenously  
• Vasopressin with nitroglycerin help to minimize systemic vasoconstriction 
• Endoscopic therapy includes injection of sclerosing agent and/or band ligation of 
varices.  
• Balloon tamponade – compressing bleeding varices temporarily  
Surgery:  portosystemic shunt 
Prevention of variceal hemorrhage :- the following drugs can be given for patients diagnosed 
to have CLD. They are not given during active variceal bleeding.  
• Non selective β-blockers (propranolol and nadolol) 
• Mononitrates (Isosorbide mononitrate) decrease portal blood flow and pressure  
3) Ascites  
• Transudative  
• Serum to ascitic albumin gradient  is > 1.1 
• Clinically detectable when larger than 500 ml 
• Most sensitive clinical sign is shifting dullness 
• Subclinical ascites can be detected by ultrasound examination. 
Management of ascites     
• Salt restriction to less than 2g/day  
• Fluid restriction if serum Na+ level is below 120 meq/l 
• Spirinolactone (aldactone) is an aldostrone antagonist, is often effective when given 
with loop diuretics.  
• Duiresis should be monitored because vigorous duiresis leads to hypovolemia and 
hypokalemia and precipitate hepatic encephalopathy. The goal of duiresis should be 
dependent on the extent of edema and be monitored by daily body weight 
measurement i.e.


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hypokalemia and precipitate hepatic encephalopathy. The goal of duiresis should be 
dependent on the extent of edema and be monitored by daily body weight 
measurement i.e. 
o  Decrease weight by 0.5 kg/day if no peripheral edema and 
o  Decrease weight by 1kg/day if peripheral edema is present. 
Refractory ascites :  
• Is defined as persistent tense ascites despite maximal diuretic therapy 
(Spirinolactone 400 mg/d, Furesemide 160 mg/d), or if azotemia develops (creatinine > 2mg/dl) while the patient is receiving sub maximal doses.


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Internal Medicine 
 
 377• It occurs in 10% of ascites of CLD origin. Such patients should be referred to 
hospitals for treatment:  
ο Repeated large volume paracentesis (with intravenous albumin replacement if 
available). But the following two modalities of therapy are available in 
developed countries. 
ο Surgical treatment (Porto-systemic shunt)   
ο Liver transplantation 
Complications of ascites 
ο Spontaneous bacterial peritonitis 
ο Hepatopulmonary syndrome  
ο Hepatorenal syndrome  
ο Rupture of the umbilicus  
a) Spontaneous bacterial peritonitis(SBP) 
• Usually due to enterobacteriacae  or pneumococci  
• Characterized by fever, abdominal pain and tenderness. Hepatic 
encephalopathy may be precipitated by the infection. 
• Diagnosis is suspected when ascitic polymorphonuclear cell count is over 
250/μl. and confirmed by ascitic fluid culture.  
• Treatment is with third generation cephalosporin for 5 -7 days.  
 
Prophylaxis for SBP 
Indications   
• Previous history of SBP 
• Patient admitted with gastrointestinal hemorrhages. 
• Ascitic protein less than 1gm/dl 
• Candidates of liver transplantation 
Drugs  
• Norfloxacin – 400 mg/day 
• Ciprofloxacin – 750 mg/once weekly or  
• Co-trimoxazole - 960mg/d for 5 days ( Monday – Friday)  
b) Hepatorenal syndrome(HRS) 
• Functional renal failure in the presence of cirrhosis.


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 378• Occurs when there is significant hepatic synthetic dysfunction and severe 
ascites.  
• Vigorous duiresis , paracentesis and sepsis may predispose to HRS 
• Typically the kidneys are histologically normal with the capacity of regaining 
normal function in the event of recovery of liver function. There is severe 
cortical vasoconstriction  
• Characterized by declining GFR, oliguria, low urine sodium (< 10 mg/l), normal 
urinary sediment and azotemia often with disproportionately high levels of blood urea nitrogen and creatinine  
• Diagnosed   after prerenal cause of renal failure is excluded. 
• Mortality rate from HRS is 95% 
   Management of HRS 
• Volume expansion to rule out volume depletion 
• Low dose vasopressin, octreotide or norepinephrine may be given  
• Liver transplantation is the accepted management.  
4) Hepatic encephalopathy (Hepatic coma or portosystemic encephalopathy)  
It is a complex neuropsychiatric syndrome that may complicate advanced liver disease and/or extensive portosystemic shunt. It manifest s in two major forms:  acute and chronic.  
Acute  
• Occurs in the setting of fulminant hepatitis 
• Cerebral edema plays a more important role  
• Mortality rate is very high  
Chronic  
• Occurs in chronic liver disease 
• Often reversible 
Pathogenesis  
• The hepatocellular dysfunction and portosystemic shunt leads to inadequate 
removal of nitrogenous compounds and toxins ingested or produced in the


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Chronic  
• Occurs in chronic liver disease 
• Often reversible 
Pathogenesis  
• The hepatocellular dysfunction and portosystemic shunt leads to inadequate 
removal of nitrogenous compounds and toxins ingested or produced in the 
gastrointestinal tract, getting access to the brain and causing hepatic 
encephalopathy.  
• The compounds commonly incriminated in causing hepatic encephalopathy include 
ο Ammonia  is very well known and studied  
ο GABA


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 379ο Mercaptans – a cause of fetor hepaticus in CLD 
ο Short chain fatty acids  
Clinical Features may involve 
• Disturbance of higher neurologic function  
• Intellectual and personality disorder  
• Dementia, inability to copy simple diagrams (constructional apraxia) 
• Disturbance of consciousness 
• Disturbance of neuromuscular function (ast erixis, hyperreflexia, myoclonous)   
• The findings are usually asymmetrical, but can also be symmetrical 
• The manifestations depend on the stage of hepatic encephalopathy 
 
Table V-6-1. Stages of chronic hepatic encephalopathy and their manifestations 
 
Stage    Clinical manifestation  
 
I Apathy, restlessness, reversal of sleep rhythm, slowed  intellect, impaired 
computing ability, impaired hand writing  
II Lethargy, disorientation, drowsiness, asterixis  
 
III Stupor (arousable), hyper active reflexes, extensor plantar responses  
IV Coma  
 
Treatment of chronic hepatic failure is based on four principles  
1) Identify and treat precipitating factors including  
• GI bleeding                                     
• Increased dietary protein                  
• Constipation                                          
• Alkalosis         
• Hypovolemia           
• Infection   
• Azotemia 
• Hypokalimia from overduiresis


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 380• CNS depressant  drugs                                                                                                                
                     
2) Reduce and eliminate substrates for the generation of nitrogenous compounds. 
• Restrict dietary protein  
ο For patients in coma  no protein should be given  
ο For non comatose patients restriction of protein to 40 - 60 gm/d is enough. 
• Cleanse the bowel with  enema in patient with gastrointestinal hemorrhage  
3) Reduce colonic bacteria that generate ammonia using oral preparations of  Neomycin 
or Metronidazole   
4) Prevent diffusion of ammonia from the bowel lumen to the blood by 
administering oral  lactulose, lactitol, or lactose (in lactase deficient patients) all of which 
are fermented by colonic bacteria to organic acids and reduce stool PH. The hydrogen ion 
produced traps ammonia in the colon and changes it to nondiffusable NH 4+ ions.  
Hepatopulmonary syndrome  
• Characterized by abnormal arterial oxygenation in a patient with cirrhosis and/or portal 
HTN. 
• Pathogenesis is thought to be due to intrapulmonary vasodilatation leading to impaired 
O2 transfer that improves with 100% O 2 
• Clinical features range from sub clinical abnormalities in gas exchange to profound 
hypoxemia causing dyspnea at rest.  
• It is a functional disorder that reverses with liver transplantation. 
 
C. Hepato cellular carcinoma (Hepatoma)


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• Clinical features range from sub clinical abnormalities in gas exchange to profound 
hypoxemia causing dyspnea at rest.  
• It is a functional disorder that reverses with liver transplantation. 
 
C. Hepato cellular carcinoma (Hepatoma) 
• One of the most frequent malignancies and important cause of mortality particularly 
in middle aged men in developing countries. The incidence is less in developed countries  
• Arises in cirrhotic liver and is closely associated with chronic hepatitis B or C. 
• Hepatitis B DNA has been shown to integrate in to the host cell genome, where it 
may disrupt the tumor suppressor genes and/or activate oncogenes. 
• Vaccination prevents  hepatitis B infection, thereby reducing the incidence of 
hepatoma  
• More common in males (male to female ratio 4:1 to 8:1)


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 381Clinical and Laboratory findings  
Common symptoms and findings 
• Abdominal pain 
• Weight loss 
• Abdominal mass                                 
• Derangement of  liver function  
Unusual manifestations  
• Bloody ascites    
• Tumor emboli          
• Jaundice    
• Gyneacomastia 
• Hepatic bruit or friction rub  
• Metabolic effect 
o Erythrocytosis  
o Hypercholesterolemia  
o Hypoglycemia  
o Hypercalcemia 
o Acquired porphyria 
•  High serum α fetoprotein level (> 400 mg/dl) 
•  Ultrasonography :Mass lesion with varying echogenicities but usually 
hypoechoic  
•  Tissue specimen: may be required to confirm the diagnosis 
•  Median survival rate is less than 6 months from the time of diagnosis 
Treatment : is usually unsatisfactory but some options include: 
• Chemotherapy 
• Radiotherapy 
• Liver transplantation. 
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, 
Chronic Hepatitis , Cirrhosis and it complications, pages 1844-1868. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition 
Medicine, Diseases of the liver, pages 249-264.


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Internal Medicine 
 
 3827. Diarrheal diseases  
 
Learning objectives: at the end of this unit the student will be able to 
1. Define diarrhea 
2. List the etiologies of acute and chronic diarrhea 3. Explain the mode of transmission of organisms causing diarrhea 
4. Describe the clinical features of diarrhea 
5. List the common complications acute and chronic diarrhea 6. Make a diagnosis of acute and chronic diarrhea 7. Manage  patients with diarrhea at the primary care level 
 
Definition : Diarrhea is defined as an increase in stool frequency and volume. The stool is 
usually liquid, and 24 hrs output exceeds 250 gm/day  Objective definition  – Stool weight greater than 200gm/day.  
• Normal stool weight is about 100 - 200 gm/d for people in developed countries who 
usually consume diets containing less fiber. 
• Stool weight is affected by fiber contents of diet, gender (higher in males), medications, 
possibly exercise and stress. 
• Normal bowel habit ranges from 3 times/day to 3 times/wk. Thus, one has to know the 
normal bowel habit of the individual and the nature of the current symptoms before the diagnosis of diarrhea 
• About 9 liters of fluid is presented to the GIT daily (7 liters from the secretion and 2 liters 
from diet). Of this only 100 - 200 ml of fluid is excreted with feces and the rest will be reabsorbed. Fluid absorption follows Na
+ absorption, which is co-transported with 
chloride ion, glucose, and aminoacids and through Na+ channels.


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from diet). Of this only 100 - 200 ml of fluid is excreted with feces and the rest will be reabsorbed. Fluid absorption follows Na
+ absorption, which is co-transported with 
chloride ion, glucose, and aminoacids and through Na+ channels. 
• Na – glucose co-transport is unaffected by many diarrheal diseases 
• Secretion follows chloride ion secretion in crypt cells, with Na+, K+ and water following 
passively through tight junctions. 
 Classification of diarrhea  
1. Based on the duration of illness diarrhea can be classified into acute and chronic  
A) Acute diarrheal disease   
• Lasts for 2 - 4 wks


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 383• It is usually infectious in origin  
• Resolves with or without intervention  
B) Chronic diarrheal diseases  
• Lasts for more than 4 wks  
• The common causes include malabsorption, in flammatory Bowel Diseases (ulcerative 
colitis), irritable Bowel syndrome, colonic cancer, and HIV/AIDS.  
• Infectious causes are not common causes of chronic diarrhea  
2. Based on the nature of diarrheal stool, acute diarrhea could be inflammatory or non-
inflammatory 
A) Non-inflammatory diarrhea   
• Is watery, non bloody diarrhea associated with periumblical cramps, nausea, and 
vomiting 
• It is small intestinal in origin 
B) Inflammatory diarrhea -  
  Dysentery  is bloody diarrhea 
3. Pathophysiologic classification   
Most diarrheal states are caused either by inadequate absorption of ions, solutes and water or 
by increased secretion of electrolytes that result in accumulation of water in the lumen.  Based on this concept diarrhea can be classified as: 
A) Secretory diarrhea:  
• Occurs when the secretion of fluid and electrolytes is increased or when the normal 
absorptive capacity of the bowel is decre ased. It usually follows stimulation by 
mediators like enteric hormones, bacterial enterotoxins (E.g. Cholera,  heat labile E. 
coli toxin, Salmonella enterotoxin ), vasoactive intestinal peptides ( VIP )  or laxatives 
. These agents activate the adenyl cyclase –cAMP system


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mediators like enteric hormones, bacterial enterotoxins (E.g. Cholera,  heat labile E. 
coli toxin, Salmonella enterotoxin ), vasoactive intestinal peptides ( VIP )  or laxatives 
. These agents activate the adenyl cyclase –cAMP system 
• These mediators block Nacl absorption and induce chloride secretion. These events 
can result in massive diarrhea, without evidence of cell injury, as shown by the ability of the cell to absorb Na
+ if coupled to nutrients (Na+ to glucose, Na+ to amino acids). 
That is why cholera and other forms of secretary diarrhea can be treated with oral solutions containing sodium and glucose. 
• Diarrhea of secretary origin persists even if the patient fasts. 
B) Osmotic diarrhea:


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 384• It occurs  due to the presence of poorly absorbed or nonabsorbable substance in the 
intestine which is osmotically active , resulting secondary accumulation of fluid and 
electrolytes. Such nonabsorbable substances include lactose in patients with lactase deficiency.  
• This type of diarrhea is usually caus ed by malabsorption and disappears when 
patient fasts for 48-72 hrs. 
C) Abnormal intestinal motility : causes or contributes to diarrhea seen in Diabetes 
mellitus , irritable bowel syndrome , postv agotomy states , carcinoid syndrome and 
hyperthyroidism, Mechanism of abnormal intestinal motility includes the following  
• If small bowel peristalsis is too rapid , an abnormal large amount of fluid and partially 
digested foodstuffs may be delivered to the colon  
• Extremely slow peristalsis may allow bacterial overgrowth to occur, and bile salts 
deconjugation to cause secondary malabsorption 
• Rapid colonic motility may not allow adequate time for the colon to absorb fluid 
delivered to the cecum (Normally 90 % of the fluid is absorbed )      
D)  Exudation : inflammations or infectious conditions that result in damage to the 
intestinal mucosa can cause diarrhea by a number of mechanisms. There is loss of 
blood, mucous proteins and serum proteins. Mucosal damage can interfere with 
absorption, induce secretion and affect motility, all of which contribute to diarrhea.                                     
 
Infectious Diarrhea


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blood, mucous proteins and serum proteins. Mucosal damage can interfere with 
absorption, induce secretion and affect motility, all of which contribute to diarrhea.                                     
 
Infectious Diarrhea  
Microbes cause diarrhea either directly by invasion of gut mucosa or indirectly through elaboration of different types of toxins: Secretory enterotoxins, cytotoxins and inflammatory 
mediators. 
I) Secretory toxin induced diarrhea 
• Patients seldom have fever or  major systemic symptoms.  
• Little or no inflammatory response. 
• The organisms colonize the intestinal mucosa but don’t invade the intestinal wall.  
     Examples:   
a) Vibrio cholerae  produces enterotoxins which stimulate adenylate cyclase which results in 
massive intestinal secretion.  
b) Enterotoxigenic E. coli  is the major cause of traveler’s diarrhea 
c)   Non typhoidal salmonella like S. typhimarium


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 385d) Shigella dysenterae  may initially cause secretary diarrhea. 
II) Cytotoxin induced Diarrhea Cytotoxins are soluble factors that directly destroy mucosal 
epithelial cells. Examples:  
a) Shigella dysenterae  produces Shiga toxin which causes destructive colitis. 
b) Enterohemorrhagic E.coli  
c) Clostridium perifringens, Vibrio parahemolyticus  
d) Clostridium defficile  causes psudomembraneous  colitis in individuals treated with 
antibiotics.  
III) Diarrhea caused by invasive pathogens. 
• Characterized by fever and other syst emic symptoms like headache and myalgia. 
• The diarrhea is frequent but small in volume. It is associated with crampy abdominal 
pain and tenesmus.  
• These pathogens induce marked inflammatory response and stool usually contains 
pus cells, proteins and often gross blood. 
Common causes include :  
Acute shigellosis 
• Feaco-orally transmitted, as few as  10 - 100 bacteria are enough to  cause diarrhea 
• Initially multiplies in the small intestine causing secretary diarrhea. Later it invades 
colonic epithelium causing bloody diarrhea.  
• Usually resolves spontaneously after 3 - 6 days. 
Acute Salmonellosis  
• Transmitted by ingestion of contaminated meat, dairy or poultry products. 
• The non typhoidal salmonellae invade primarily the distal ileum.  
• Causes short lived (2 – 3 days) illness characterized by fever, nausea, vomiting and


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• Transmitted by ingestion of contaminated meat, dairy or poultry products. 
• The non typhoidal salmonellae invade primarily the distal ileum.  
• Causes short lived (2 – 3 days) illness characterized by fever, nausea, vomiting and 
diarrhea. This is in marked contrast to the 3 - 4 wks febrile illness caused by Salmonella typhi and paratyphi, which are not usually associated with diarrhea. 
Campylobacter jejuni   
• It may be responsible for up to 10% of acute diarrhea world wide. It invades both 
the small and large intestines. 
Enterohemorrhagic E. coli  ; 
• It produces bloody diarrhea without evidence of mucosal inflammation (grossly 
bloody stool with few or no leucocytes).


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 386 Viral causes of diarrhea  e.g. Norwalk and Rota viruses  
• Invade and damage villous epithelial cells  
• Cause diarrhea by interfering with absorption through selective destruction of 
absorptive villous tip cells with sparing of secretary crypt cells. 
• Stool is usually watery and its content resembles those of noninvasive diarrhea, with 
few inflammatory cells, probably because of absence of colonic damage.  
 
Protozoal cause of diarrhea 
a) Giardia lamblia. 
• few organisms are necessary to cause infection 
• Multiplies in the small intestine, attach to and occasionally invade the mucosal cells. 
• Its clinical features span from an acute diarrheal illness to chronic diarrhea 
associated with malabsorption and weight loss 
• Diagnosis  is based on  identification of the organism either in the stool or duodenal 
mucus or by small intestine biopsy. Cysts or trophozoites can be identified in the 
stool, and treatment should be given in both cases. 
b) Entamoeba histolytica  may cause syndromes ranging from mild diarrhea to 
fulminant amoebic colitis with multiple bloody stools, fever and severe abdominal pain.  
c) Cryptosporidium parvum and Isospora belli  occasionally cause self limited acute 
diarrheal illness in otherwise healthy individuals. They may cause voluminous life threatening diarrheal diseases in patients with acquired immunodeficiency syndrome. 
Modified acid fast staining of the stool will identify both organisms.


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diarrheal illness in otherwise healthy individuals. They may cause voluminous life threatening diarrheal diseases in patients with acquired immunodeficiency syndrome. 
Modified acid fast staining of the stool will identify both organisms. 
 
Evaluation of a patient with diarrhea 
Careful interview of patients with diarrhea contributes in etiologic diagnosis, evaluation of 
severity of illness, and in designing treatment and preventive measures. Thus, the history 
should include 
 Duration of illness:  if the diarrhea lasts for 2 - 4 wks, acute diarrheal diseases are said to 
exist. These are usually infectious in origin  and resolve with or without intervention. 
However, if it lasts for more than 4 wks, consider chronic diarrheal diseases and infectious 
causes are unlikely. In such cases the common causes include malabsorption,


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Internal Medicine 
 
 387inflammatory Bowel Diseases (ulcerative colitis), irritable Bowel syndrome, colonic cancer, 
and immuno suppressions like AIDS.  
Diurnal variation – is there any relation to any part of the day? 
 Nocturnal – organic causes  
 Non nocturnal – functional causes like irritable bowel syndrome 
Is the diarrhea watery or bloody? 
       Bloody diarrhea is usually inflammatory  or ischemic in origin and caused by invasive 
organisms, ulcerative colitis, or neoplasms     
Volume of diarrhea  
Large volume diarrhea indicates small bowel or proximal colonic diseases  
Scanty, frequent stools associated with urgency suggest left colon or rectal diseases  
Any association with specific meal ?  If diarrhea is associated with intake of 
 Fat – it is due to fatty intolerance 
 Sweet diet – it is due to osmotic diarrhea  Milk and milk products - it is due to lactase deficiency  
Is there history of drug intake?  
Penicillin may be associated with psudomembraneous colitis.  
Laxatives Chemotherapeutic agents 
       7) Presence of underlying diseases (like diabetes mellitus) or systemic symptoms  
Physical examination:  Assess severity of dehydration, Wight loss and other associated signs 
in patient with chronic diarrhea.  
Diagnosis:  
Laboratory tests: 
1) Culture and sensitivity testing to detect a pathogenic bacterial strains. A positive 
stool culture is found for 40 % of patients who have  WBC in the stool  and fever


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in patient with chronic diarrhea.  
Diagnosis:  
Laboratory tests: 
1) Culture and sensitivity testing to detect a pathogenic bacterial strains. A positive 
stool culture is found for 40 % of patients who have  WBC in the stool  and fever 
2) Microscopic examination:  to identify ova and parasites  
3) Guaiac :  to detect occult blood  
4) Sudan staining:  to detect fat droplets. 
5) Wright or methylene blue staining: to detect WBC, which are indicative of invasive 
infectious causes of diarrhea. 
Proctosigmoidoscopy:  to exclude of confirm the diagnosis of inflammatory bowel diseases. 
 
Management


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 3881. Rehydration 
• In patients with massive diarrhea and vomiting with hypotension intravenous fluids 
like Ringer’s lactate or Normal saline should be given in adequate amount. 
• For patients without hypotension oral fluid containing sodium, glucose, potassium and 
chloride ions (ORS) are preferred. 
2. Antimicrobial therapy 
Antibiotics:  
• Most acute infectious diarrheal diseases do not require antibiotic therapy because 
majority of them are self limited and viral in nature.  
• Of the non invasive bacterial diarrhea, antibiotics decrease the volume of diarrhea 
only in cholera. Doxycycline 300mg single dose is the drug of choice. 
• For invasive bacterial diarrhea caused by E. coli  and Shigella  (bacillary dysentery)   
Ciprofloxacin 500 mg or Norfloxacin 400mg twice a day for 3-5 days is indicated. 
Anti-protozoal: 
• For Entamoeba histolytica : Metronidazole 500mg PO TID for 7 days  
• For Giardia lamblia:  Metronidazole 250mg thrice a day for 5 days or Tinidazole 2g 
once. 
• For Isospora belli:   Co- trimoxazole 960mg four times a day for 10 days then 960mg 
twice a day for additional three wks . In immunocompromized patients continue maintenance dose of the same drug three times a week. 
• When no specific therapy is available or no cause is identified it’s appropriate to give 
empirical therapy E.g. 
o Antibiotics for possible bacterial overgrowth or Metronidazole for Giardia, 
cholesteramine for bile acid malabsorption or


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• When no specific therapy is available or no cause is identified it’s appropriate to give 
empirical therapy E.g. 
o Antibiotics for possible bacterial overgrowth or Metronidazole for Giardia, 
cholesteramine for bile acid malabsorption or  
o Non specific therapy with constipating agents such as loperamide, diphenoxylate 
and in more severe cases codeine or long acting somatostatin analogue.  
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th Edition, Diarrhea,    
pages 225-229. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd edition Medicine, 
Diarrhea, 210-224.


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Internal Medicine 
 
 389CHAPTER SIX 
HEMATOLOGIC DISORDERS 
 
1. Anemia 
Learning objectives:   At the end of this topic the student we be able to:-   
1. Define anemia and describe the diagnostic criteria of anemia in adults. 
2. Understand  factors that influence Hematocrite / Hemoglobin values 
3. Evaluate cases of anemia with appropriate history, physical examination and proper 
laboratory studies 
4. Describe classification of Anemia. 
5. Understand the adaptive mechanisms to chronic anemia. 6. Understand the principles of management of anemia.                                        
           
Anemia: General approach  
a) Definition  
• Functional definition : A significant reduction in red cell mass and a corresponding 
decrease in the 0 2 carrying capacity of the blood. 
• Laboratory definition : A reduction of the Hemoglobin concentration, red cell mass 
or Hematocrite, to below normal levels. 
• In women of the child bearing age, their blood values are 10% lower than men. 
Therefore, Anemia may be defined as a HCT of less  than 10% below the mean values for age, sex and altitude  
 
Table VI-1-1 Criteria of anemia in adults at sea level  
                           
Factor
 
 Women  Men 
RBC x 1012/ L < 4.0 < 4.5 
Hgb (g/dl)  < 12  < 14 
HCT (% )  < 37 < 40 
 NB:  blood values may not accurately reflect alteration in red cell mass. For instance;


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 390• Hgb or Hematocrite could be falsely elevated ( ↓ plasma volume) e.g. 
hemorrhage, burns, vigorous diuresis, dehydration all leading to 
Hemoconcentration  
• Hgb or Hct may be falsely low ( ↑ plasma volume) leading to  Hemodilution  
E.g.  Spleenomegaly, CHF, Cirrhosis, pregnancy  
 
Epidemiology 
• In Ethiopia, a study conducted by Zein Ahmed Zein in Gondar, rural  population 
indicated a  prevalence rate of anemia to be very high ( 40.5%, ), and  anemia was the fourth leading cause of hospitalization and hospital deaths in 1982 in Gondar. 
• Another study done in Black lion Hospital in 1987 G.C. showed that anemia is the 3
rd 
cause of hematology admissions.  
• Analysis of admissions to hospitals in Ethiopia showed that anemia accounted for 0.5 - 
4% of all admissions and 25% of hematological diseases related admissions. 
• Iron deficiency anemia is the commonest ty pe of anemia globally, mainly in developing 
countries like Ethiopia.   
• Sickle cell disease and thalassemias are not reported in Ethiopia but common in other 
African countries. Hereditary hemolytic anemias aren’t common in our country . 
 
Clinical approach to the Patients with anemia  
Anemia is a manifestation of an underlying pathological condition.  
It results from:  
1. Under production  
2. Increased destruction/Hemolysis   
3. Blood loss /bleeding 4. Multifactorial :  a combination of these


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Anemia is a manifestation of an underlying pathological condition.  
It results from:  
1. Under production  
2. Increased destruction/Hemolysis   
3. Blood loss /bleeding 4. Multifactorial :  a combination of these              
History:  Accurate history provides information crucial to the diagnosis of the underlying cause.                   
• Nutritional /Dietary history       
• Underlying diseases   
• Blood loss : GI or Genito uirinary blood loss      
• Family history of anemia     
• Exposure to drugs/toxins E.g.  - Methyldopa  
• Ggeographical location


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 391• Pregnancy 
      
Symptoms :   
• Depend on the rapidity of development of anemia, age of the patients, the presence of 
an underlying disease .They are often non-specific  
• Fatigue, dizziness, dyspnea, palpitation, syncope, exercise and cold intolerance, angina,  
• Tinnitus, vertigo, throbbing head ache,  
• Anorexia, indigestion, nausea, bowel irregularity (due to shunting of blood from the 
splanchinic bed) 
• Irritability, difficulty in concentration, worsened dementia and. 
• Impotence or decreased libido 
• Intermittent claudication 
Physical Examination: 
       A comprehensive examination with em phasis to the following findings should be made. 
• Skin and mucous membrane: look for pallor, icterus, bleeding sites, leg ulcer 
• Spooning of fingernails → in iron deficiency anemia  
• Atrophy of the tongue, sore tongue (glossitis), angular stomatitis which may be seen in 
iron deficiency anemia. 
• Abdomen: spleenomegaly, hepatomegaly, evidence of gallstone. 
• Pelvic and rectal examination: to look for possible site of bleeding. 
• Bone tenderness and Lymphadenopathy to rule our hematologic malignancies and  
• Neurological: gait, reflexes, vibration and position sense which may help to look for 
neurologic changes associated with Vit B- 12 deficnecy.  
• Fundoscopy: retinal hemorrhage 
• Cardiovascular system; modest tachycardia, wide pulse pressure hyper dynamic


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neurologic changes associated with Vit B- 12 deficnecy.  
• Fundoscopy: retinal hemorrhage 
• Cardiovascular system; modest tachycardia, wide pulse pressure hyper dynamic 
precordium, flow murmur. In severe form of Chronic anemia patients may develop CHF 
with S3 gallops. 
 
Laboratory study 
1. Complete blood count  
Hgb, Hct, ESR, Platelet count, WBC with differential


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 3922. Red blood cell indices  
a. Mean Corpuscular volume ( MCV): Hct/RBC : normal value is 80 – 95 fl 
b. Mean corpuscular Hemoglobin( MCH ) : Hgb/RBC : 27 – 32 pg 
c. Mean corpuscular Hemoglobin (MCHC): Hgb/Hct 32 – 36%               
3. Examination of the peripheral blood smear: examine a cellular morphology, shape, 
size, color, abnormality of other cells. 
             Red cell morphology       
• Normochromic Normocytic  RBCs are aeen in normal individuals and in anemia of 
chronic diseases 
• Anisopoikilocytes: Variation in size a nd shape may be seen in iron deficiency anemia  
• Hypochromic microcytic anemia: is seen in iron defeciency anemia , anemia of 
chronic diseases  , thalassemia and sideroblastic anemia (SBA) 
• Macrocytic RBCs : Macro – ovalocytes with hyper segmented neutrophils Æ indicate 
megaloblastic anemia and myelodysplasia  
• Schistocytes (fragmented RBC/Helmentcells):- microangiopathies , DIC, vasculitis, 
prosthetic heart valve 
Classification of anemia  
A. Pathophyisiologic Classifications  (based on underlying disease) 
1) Anemia associated with impaired RBC Production 
a) Aplastic anemia                        
b) Iron deficiency                                                     
c) Myelodysplastic syndrome.                    
d) Megaloblastic anemia  
e) Anemia of CRF 
f) Anemia of chronic diseases  
g) Drug related      
2) Anemia associated with increased RBC loss or destruction  
a) Bleeding


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c) Myelodysplastic syndrome.                    
d) Megaloblastic anemia  
e) Anemia of CRF 
f) Anemia of chronic diseases  
g) Drug related      
2) Anemia associated with increased RBC loss or destruction  
a) Bleeding  
b) Hereditary hemolytic anemia  
i) Hemoglobinopathies,  sickle cell disease, Thalassemia 
ii) Primary disorder of RBCs iii) RBC erythropathies (G6 PDH, PK deficiency) 
c) Acquired hemolytic anemia


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Internal Medicine 
 
 393i) Autoimmune     
ii) Drug induced hemolytic anemia                iii) Microangiopathies (e.g. DIC) 
iv) Traumatic 
B. 
Morphological classification  
1) Hypochromic microcytic anemia  
a) Inherited: Thalassema, sideroblastic anemia  
b) Acquired: IDA, Anemia of chronic diseases 
2) Macrocytic anemia :  (MCV > 100 fl) 
a) With megaloblastic marrow: megaloblastic anemia  
b) With normoblastic marrow: Hemolysis, acute bleeding,  
3) Normchromic normocytic:-   
a) Anemia of chronic disease  
b) Early iron deficiency anemia  
c) Aplastic anemia  
d) Anemia of CRF  
Adaptation to chronic anemia : the main consequence of anemia is tissue hypoxia  
Compensatory mechanisms:  
1.  Intrinsic red cell adjustments (adaptations) 
• Modulation of O 2 affinity by increased generation of 2,3- diphosphoglycerate in 
erythrocytes  
• It bounds to Hgb, causing a right ward shift in O 2- Hgb dissolution curve 
⇒ This allows more O 2 to be unloaded from the RBC at any given blood O 2 tension 
2. Cardiovascular adjustment  
• Increased in cardiac  output occurs at Hgb level of 7-8 gm% : the increased in cardiac 
output coupled with modest tachycardia  creates a  hyperdynamic state and hence 
systolic ejection murmur  
• Peripheral vascular resistance decreases there by  facilitating tissue perfusion; 
clinically is evidenced by wide pulse pressure. 
3. Local changes in tissue perfusion:  Redistribution of blood flow to vital organs at the


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• Peripheral vascular resistance decreases there by  facilitating tissue perfusion; 
clinically is evidenced by wide pulse pressure. 
3. Local changes in tissue perfusion:  Redistribution of blood flow to vital organs at the 
expense of reduced blood flow to less vital organs. 
4.  Reduction of mixed venous O 2 tension to increases the arterio–venous O 2 difference ⇒ ↑ 
O2 extraction at peripheral tissues


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Internal Medicine 
 
 394Individuals tend to survive at extremely low hemoglobin levels (even as low as 3 gm %) due to 
these compensatory mechanisms.  
Therapeutic considerations and indications 
In the management of anemic patients carefully remember the following points  
• Identify and correct the cause of anemia  
• Administration of Hematinines such as Iron, Vit B 12 or folate without correct diagnosis 
of the cause of anemia is an unacceptable practice in the treatment of anemia  
• Therapeutic modalities include: Iron, folate, Vit. B 12, pyridoxine (B 6) blood transfusion, 
steroids (in hemolytic anemia) splenectomy, erythropoietin, bone marrow transplant (aplastic anemia), and androgens 
• Carefully weigh the risks of blood transfusion over its advantage. 
When to transfuse blood in chronic anemia  
1. Anemia severe enough to cause CHF (congestive heart failure) 2. Hypoxic manifestations: Irritability, unconsciousness, angina  3. Surgical or gynecologic patient awaiting surgery  
NB:  no threshold of Hct/Hgb that mandates transfusion; the decision to administer blood must 
be based on the functional status and symptomatology of the patient. 
• Consider risk of blood transfusion 
• Adhere to blood component transfusion (packed RBC, FFP, cryoprecipitate, 
platelets) 
• Consider whole blood only when there is volume loss due to hemorrhage. 
 
I. Micorocytic Anemias 
A) Iron deficiency anemia (IDA)


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• Adhere to blood component transfusion (packed RBC, FFP, cryoprecipitate, 
platelets) 
• Consider whole blood only when there is volume loss due to hemorrhage. 
 
I. Micorocytic Anemias 
A) Iron deficiency anemia (IDA) 
Learning objectives: at the end of this topic the student will be able to:-  
1. Understand iron metabolism 2. Describe the characteristic features of iron deficiency anemia (IDA)  3. List the various causes of iron deficiency anemia ( IDA) 4. Know the clinical manifestations and common specific laboratory findings of iron 
deficiency anemia (IDA) 
5. List some of the differential diagnosis of iron deficiency anemia (IDA) 6. Understand the management of  iron deficiency anemia (IDA)


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Internal Medicine 
 
 3957. Identify possible reasons for inadequate response to therapy and indications for 
parenteral iron administration 
8. List the possible causes of anemia of chronic diseases with their features, 
pathogenesis and principles of therapy   
 
Definition : - Iron deficiency anemia occurs when body iron stores become inadequate for the 
needs of normal RBC production (erythropoiesis)   
It’s characterized by: 
o Hypochromia and microcytosis of the circulating erythrocytes ( RBCs) 
o Low plasma iron and ferretine concentration. 
o A transferrin saturation of < 15% (Normally ∼ 35%)  
• Iron deficiency anemia is a manifestation of diseases, not by itself a complete diagnosis  
• It is the commonest cause of anemia world wide  
Introduction 
Iron metabolism:  
• Daily 10-30mg iron ingested, 5-10% absorbed to balance precisely the amount lost 
(1mg) under physiologic condition  
• Amount absorbed can increases up to five fold  if body iron store are depleted or 
erythropoiesis is accelerated.  
• Absorbed as hem and non hem iron in the duodenum and proximal jejunum  
Iron absorption: 
• Is facilitated by: Stomach acidity, Ascorbic acid, citrates, while  
• Is limited/reduced  by : Phosphates, Oxalates, TTC, Tannates (tea) and pyrates (plant 
food) 
Transferrin is the transport protein that carries iron in the plasma and ECF.  
Sequences of events in the development of IDA 
1. Mobilization and depletion of iron stores


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food) 
Transferrin is the transport protein that carries iron in the plasma and ECF.  
Sequences of events in the development of IDA 
1. Mobilization and depletion of iron stores  
2. Decreased plasma Fe2+ and Ferretine concentration 
3. Iron deficient erythropoiesis  
4. Iron deficiency anemia – Hypo chromic  microcytic cells   
Etiologies of Iron deficnecy Anemia  
1. Chronic blood loss  
• Uterine


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Internal Medicine 
 
 396• Gastrointestinal, e.g. esophageal varices; Hi atal hernia; peptic ulcer disease; aspirin 
ingestion;  Carcinoma of the stomach, ceacum, colon or rectum; hook worm 
infestation ;  colitis; piles; Diverticulosis; etc 
• Rarely hematuria, hemoglobulinuria, pulmonary hemosiderosis, self inflicted blood 
loss  
• Disorders of hemeostasis, intravascular hemolysis  
2. Increased demands  
• Prematurity in newborns  
• Rapid growth ( as in adolescent ) growth spurt 
• Pregnancy  
3. Mal absorption of iron  
• Gastrectomy, Celiac disease  
4. Poor diet 
        ⇒  Contributory factor in many countries but rarely sole cause  
 
Clinical manifestation:  
• Is insidious in onset and progressive in course 
• Patients often present with nonspecific symptoms mentioned above with/without 
some specific symptoms. 
Specific symptoms  
• Pica: craving for unusual food substance (amylophagia, geophagia, pagophagia) 
• Increased GI absorption of lead – lead poisoning 
• Koilonychia – spooning of the finger nails  
• Plummer – Vinson/Peterson - Kelly syndrome: characterized by IDA, koilonychia, 
and dysphagia due to post cricoid esophageal web)  
Laboratory findings  
A) Peripheral blood morphology and RBC indices  
• ↓MCV, ↓MCH, ↓MCHC  and hypochromic microcytic RBCs with occasional target 
cells and pencil-shaped poikilocytes  
• ↓ reticulocyte count  
• Dimorphic peripheral films ( mixed Normal RBCs and microcytic hypochromic RBCs )


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• ↓MCV, ↓MCH, ↓MCHC  and hypochromic microcytic RBCs with occasional target 
cells and pencil-shaped poikilocytes  
• ↓ reticulocyte count  
• Dimorphic peripheral films ( mixed Normal RBCs and microcytic hypochromic RBCs )   
o Combined Iron and folate /B 12 deficiency 
o On those with recent iron therapy


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Internal Medicine 
 
 397o Those with recent blood transfusion  
B) Serum iron and total iron – binding capacity (TIBC) 
• ↓  serum iron and ↑ TIBC (hence IBC is < 10% saturated). This is in contrast to other 
forms (e.g. ACD). 
C) Serum ferritine is decreased  
D) Free erythrocyte protoporphyrine (FEP): non specific  
• It increased during early phase of iron deficiency anemia, lead poisoning, 
sideroblastic anemia and in erythropoietic porphyria.  
E) Bone marrow iron  
• Complete absence of iron from stores (macrophages) and absence of siderotic iron 
granules from developing erythroblasts  
F) Investigation to establish the underlying  cause   
• Stool for occult blood  
• CXR to exclude pulmonary hemosiderosis 
• U/A for hematuria or hemosiderinuria 
• Pelvic – gynecologic studies  
• Cr- labeling of RBCs with 5 day collection of stools 
• Upper and lower GI radiologic and Endoscopic studies  
• Bronchoscopy 
 
Differential diagnosis of hypochromic, microcytic anemia   
A. With ↓ body iron stores – IDA 
B. With normal body or ↑ body iron store 
i) Impaired iron metabolism: Anemia of chronic diseases (ACD) 
ii) Disorder of globin synthesis: Thalassemia iii) Disorders of hem synthesis: sideroblastic anemia 
iv) Both impaired iron metabolism and defecti ve globin synthesis:  lead poisoning  
 
Treatment of Iron deficiency Anemia  
1. Identify underlying cause and treat it  
2. Correct anemia  and replenish stores  by oral iron,


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iv) Both impaired iron metabolism and defecti ve globin synthesis:  lead poisoning  
 
Treatment of Iron deficiency Anemia  
1. Identify underlying cause and treat it  
2. Correct anemia  and replenish stores  by oral iron, 
•  Ferous sulfate 300mg (60 mg elemental iron)   3x/day for  4-6 months


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Internal Medicine 
 
 398Absorption increased by  giving between meals, but side effects are less if 
given with meals  
Common Side effects ; GI upset, nausea, dyspepsia, constipation /diarrhea. If 
the side effects are not tolerable, reduced dose or change brand e.g. to ferrous gluconate or ferrous lactate syrup.  
• Response to treatment;  an expected daily rise of hemoglobin by 0.1-0.2 gm /dl 
in  
• Follow-up ; reticulocytosis will start at 3-4 days and peak on the 10
th day of 
initiation of treatment. 
• An increase in Hgb concentration of at least 2gm/dl after 3wks of therapy is 
considered as a good response. 
• Treatment should be continued for about 3 months after resolution of anemia to 
replenish the iron store. 
Inadequate  response  may imply 
• Continuing hemorrhage  
• non compliance to therapy 
• Wrong diagnosis 
• Mixed deficiency – associated folate or vit.B 12 deficiency  
• Another cause for anemia e.g. malignancy, inflammation  
• Malabsorption – rare cause 
• Use of slow release preparations  
Parentral iron  
 Indications:  
1. Oral Iron intolerance despite modification in dosage regimen 
2. Malabsorption 3. Inability or unwillingness to take orally  
• Iron-dextran  complex  or iron sorbitol  citrate  can be used Intra-muscularly or intra-venous 
route. 
Dose (ml)  = 0.0442 (desired Hgb – Observed Hgb.) X weight (Kg.) + (0.26 x weight Kg.) 
 
B)  Anemia of chronic diseases (ACD)


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• Iron-dextran  complex  or iron sorbitol  citrate  can be used Intra-muscularly or intra-venous 
route. 
Dose (ml)  = 0.0442 (desired Hgb – Observed Hgb.) X weight (Kg.) + (0.26 x weight Kg.) 
 
B)  Anemia of chronic diseases (ACD) 
It occurs in association with a variety of chronic inflammatory and malignant diseases.


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Internal Medicine 
 
 399Etiologies   
1) Chronic inflammatory diseases  
a) Infections e.g. pulmonary abscess, TB, Osteomyelitis, pneumonia, bacterial 
endocarditis  
b) Non infectious , e.g. Rheumatoid arthritis, SLE (systemic lupus erythematous) and other 
connective tissue diseases, sarcoidosis, Crohn’s disease  
2) Malignant diseases  
E.g. carcinoma, lymphoma, sarcoma  
 Characteristic features are: 
• NCNC or mildly hypochromic indices and red cell morphology  
• Mild and non progressive anemia (Hgb rarely < 9.0g/dl) : Severity being related to 
severity of underlying disease 
• Both serum iron and TIBC are reduced 
• Serum ferritine is normal or raised and  
• Bone marrow storage  iron is normal but erythroblast iron is reduced  
 
Pathogenesis is related to release of cytokines which mediate 
• Decreased release of iron from macrophages to plasma,  
• reduced RBC life span ( ∼ 80 days) in effective erythropoiesis  
• Inadequate erythropoietin response to anemia  
Treatment of Anemia of Chronic Dideases: 
1. Correction of underlying disease 
2. Erythropoietin (40-80 % success rate) 
3. Correction of reversible contributors (iron, folate, cobalamine supplements if necessary) 
 
C) Sideroblastic anemia: 
• Refractory anemia with hypochromia with ↑ marrow iron  
• Many pathological ring sideroblasts are found in the bone marrow  
• Is caused by defect in hem synthesis  
Classification: 
• Hereditary (sex linked recessive trait) 
• Acquired


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Internal Medicine 
 
 400o Primary :Myelodysplasia  
o Secondary : 
- Malignant diseases of the marrow  
- Drugs e.g. cycloserin alcohol, lead 
- Others: hemolytic anemia, megaloblastic anemia, malabsorption  
∼ 15% of marrow erythroblasts are ring sideroblasts in hereditary and 10 acquired forms.  
Lead poisoning  
• Inhibits both hem and globin synthesis  
• Interferes with breakdown of RNA by inhibiting the enzyme pyrimidine- 5 
nucleotidase ⇒ accumulation of denatured RNA in red cells giving rise to Basophilic 
stippling . 
• Hypo chromic/Hemolytic anemia with bone marrow ring sideroblasts 
• Free erythrocyte protoporphyrin is raised  
Management:  
• Pyridoxine, folic acid therapy : may bring some response  
• Repeated transfusion is ultimate choice  
 
II. Macrocytic Anemia 
Learning objectives : at the end of the student will be able to:- 
1. Define Megaloblastic anemia (MA) 
2. Understand the pathogenesis of Megaloblastic anemia (MA) 3. List causes of Megaloblastic anemia (MA) 
4. Compare and contrast various forms of MA 
5. Identify the possible underling cause of Cobalamine deficiency 6. Understand the management of Megaloblastic anemia and asses response to therapy 
properly 
 
Megaloblastic Anemia and other Macrocytic Anemia 
 Pathogenesis : It’s a descriptive morphologic term in which maturation of the nucleus is delayed


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properly 
 
Megaloblastic Anemia and other Macrocytic Anemia 
 Pathogenesis : It’s a descriptive morphologic term in which maturation of the nucleus is delayed 
relative to that of cytoplasm. The delay in maturation of the nucleus is attributed to defective DNA synthesis. This condition leads to Megalobl astic marrow and ineffective erythropoiesis.


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Internal Medicine 
 
 401The immature erythroblasts are destroyed within the bone marrow leading (Intramedulary 
hemolysis) which results Megaloblastic anemia .  
Etiologies of megaloblastic anemia  
1. Vitamin B 12 deficiency  
2. Folate deficiency 3. Abnormalities of vitamin B
12 or folate metabolism, transcobalamine deficiency,  
antifolate-drugs  
4. Other defects of DNA synthesis: congenital enzyme deficiency, alcohol, treatment with 
hydroxyurea, etc. 
Cells primarily affected are those with rapid turnover: 
• Hematopoietic cells (RBCs, granulocytes, megakaryocytes) 
• Cells derived from Respiratory tract and  GIT etc 
Macrocytic RBCs appear before the onset of anemia  
 Table VI-1-2 Difference in between Cobalamine and Folate physiology and daily 
requirement   
Feature  Cobalamine  Folate  
Source Animal products (meat, diary 
product) Vegetables, fruits  and  
animal product  
Daily requirement 2-5 µg   100 mg (50-200mg) 
Body store 3-5(4) mg 5-20 mg 
Time to develop anemia after the underlying cause for deficiency  3-4 years 4-6 months 
Cooking Little effect easily destroyed 
Plasma transport Specifically bound by 
Transcobalamine ( Tc. I, II, III) 2/3 easily bound to albumin, 1/3 is free 
Usual therapeutic form Hydroxocobalamine   Folic acid


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Internal Medicine 
 
 402Causes of Vit. B 12 deficiency  
1) Nutritional : especially in vegans  
2) Malabsorption  
a) Gastric causes  
i) Adult (addisonian) pernicious anemia  
ii) Congenital lack or abnormality of intrinsic factor  iii) Total or partial gastrectomy  
b) Intestinal causes  
i) Intestinal stagnant loop syndrome, jejunal diverticulosis, blind loop, stricture etc. 
ii) Chronic tropical sprue  iii) Ileal resection and Crohn’s disease  iv) Congenital selective mal absorption with proteinuria  
v) Fish tapeworm : Diphlobotrium 
 
Pernicious anemia: 
Results from immunologic destruction of the Parietal cells in the stomach, which produce 
intrinsic factors, as in chronic atrophic gastr itis, which results impaired production of intrinsic 
factors. Nearly 90% of patients show parietal ce ll antibody, 50% have type I or blocking antibody 
to intrinsic factor (IF) and 35% show type II or precipitating antibody to IF. 
• MCV is increases  
• Bone marrow : Hyper cellular and megaloblasts 
• Peripheral film : neutrophilic hypersegmentation indicated by  
 1 neutrophil with 7 segments  
 2-3 neutrophils with 6 segments or    
 > 5 neutrophils with 5 segments  To differentiate from folate deficiency biochemical tests should be done: 
• Serum folate would be normal in patients given over-night dose or  
• Determination of RBC folate level  
Schilling test (3 phases)  helps to identify the underlying cause of Vit.B
12 deficiency.


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• Serum folate would be normal in patients given over-night dose or  
• Determination of RBC folate level  
Schilling test (3 phases)  helps to identify the underlying cause of Vit.B
12 deficiency. 
1) Radioactive cobalamine is given orally + un labeled cobalamine intra muscularly (to saturate 
body needs). Then 24 hours urine cobalamine excr etion is should be determined . Normally 
>8% should be excreted. If the excretion rate is < 8% , it may indicate malabsorption to Vit B
12 .


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Internal Medicine 
 
 4032)    Labeled cobalamine  bound to IF is given orally  
In pernicious anemia Vit B 12 absorption is corrected i.e. the daily urinary excretion rate is 
>8% 
In patients with abnormal in terminal ileum or pancreatic insufficiency Vit B 12 absorption will 
not be corrected  
3) Phase 2 repeated after 2 weeks of antibiotics  
• Vit B 12 absorption is corrected in patients with bacterial over growth such as (blind loop 
syndrome) 
• Administration of pancreatic extract corrects pancreatic insufficiency. 
• Lack of/by pass of ileal intrinsic factor receptor (terminal ileal disease) or defective trans 
enterocyt cobalamine transport can’t be corrected. 
 
Treatment of megaloblastic anemia  
1. Vit B12 Deficiency:   is treated with  Hydroxocobalamine  which is given parentraly   
• Dose: Initial dose: 6 x 1000 µg over 2-3 weeks and Maintenance : 1000 µg every 3 
months 
• Prophylactic therapy  is indicated in patients with Total gastrectomy and Ileal resection 
2. Folate deficiency:  is treated with Folic acid preparation which is given orally   
• Dose : 5 mg Po daily  
• Prophylactic therapy  is indicated in pregnancy, sever hemolytic anemia, in patients 
with dialysis, and premature newborns  
3. Additional measures: 
• Correct underlying cause 
• Antibiotics for bacterial over growth and treatment of fish tapeworm  
Response to therapy  
• Feeling of general well being is restored  in 48 hrs  
• Reticulocytosis begins in 3-4 days and peaks in 7-10 days.


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• Correct underlying cause 
• Antibiotics for bacterial over growth and treatment of fish tapeworm  
Response to therapy  
• Feeling of general well being is restored  in 48 hrs  
• Reticulocytosis begins in 3-4 days and peaks in 7-10 days. 
• If both folate and cobalamine deficiency present give cobalamine first


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Internal Medicine 
 
 404References:  
1) Kasper L., Braunwald E., Harrison’s principles of In ternal medicine, 16th Edition,  Anemia,      
pages 586-624.  
2) Myers R. Allen, National Medical Series for independent Study ( NMS ) 3rd edition 
Medicine, Anemia,  pages 109-115.


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Internal Medicine 
 
 4052. Leukemias 
 
Learning Objective: At the end of this unit the student will be able to 
1) Define leukemia   2) Classify the different types of leukemias    3) Describe the possible etiologies and epidemiology of leukemia. 
4) Identify the clinical features of leukemia 
5) Make presumptive diagnosis and refer to hospitals where special investigations can be 
done 
 
Definition 
• Leukemias are neoplasms of hematopoitic cells proliferating in the bone marrow initially 
and then disseminate to peripheral blood,  lymph nodes, spleen, liver etc.   
• Lymphomas differ from leukemias in that, lymphomas arise primarily from lymph nodes 
but spread to blood and bone marrow only in "leukemic phase” of the diseases. 
Classification of leukemias - is based on 
1. Cell of origin : there are two types of leukemias 
• Lymphoid leukemias 
• Myeloid leukemias 
      2. Clinical course of the disease  - two forms of presentation of leukemias 
• Acute leukemias 
• Chronic leukemias 
Thus, combining the above two criteria, there are have 4 main types of leukemias 
A) Acute lymphoblastic leukemia (ALL) 
B) Chronic lymphoid leukemia (CLL) 
C) Acute myelogeneous leukemia (AML) 
D) Chronic myeloid leukemia (CML) 
Etiology 
The etiologies of leukemias are unknown in most of the cases. But studies have demonstrated 
that both genetics and environmental factors are important in the causation of these diseases. 1. Genetics


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D) Chronic myeloid leukemia (CML) 
Etiology 
The etiologies of leukemias are unknown in most of the cases. But studies have demonstrated 
that both genetics and environmental factors are important in the causation of these diseases. 1. Genetics 
• There is a greatly increased incidence of leukemia in the identical twin of patients 
with leukemia.


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Internal Medicine 
 
 406• Increased incidence of leukemia also occurs in people with chromosomal 
abnormalities such as Down’s syndrome (trisomy 21).  
2. Environmental factors like 
• Ionizing radiation : The relation between acute leukemia and ionizing radiation, has 
been established in those having occupational radiation exposure, patients receiving 
radiotherapy and Japanese survivors of atomic bomb explosions.  Radiation 
exposure increases the risk of CML, AML and ALL.  No known relation with CLL. 
• Chemicals  like benzene, aromatic hydrocarbons, and treatment with alkylating 
agents and other chemotherapeutic drugs.  Exposure to such chemicals is associated with increased risk of developing AML. 
• RNA based retroviruses Infection with HTLV - I is related to human T-cell leukemia & similarly Epstein Barr virus is related to ALL (T
3 subtype) and aggressive lymphoma. 
 
Epidemiology 
• Globally the incidence of all leukemias is 13/100,000/ year usually affecting men more 
than women.   
• Certain leukemias are more common in a particular age group than the other, i.e. acute 
lymphoblastic leukemia (ALL) is common in children and young adults whereas AML, 
CLL and hairy cell leukemia are common in adults with peak between the 6th & 7th 
decade.  
• A Study conducted in one of the teaching hospitals in Ethiopia has shown that leukemias 
were the commonest, accounting for about 35.5% of hematological admissions and


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decade.  
• A Study conducted in one of the teaching hospitals in Ethiopia has shown that leukemias 
were the commonest, accounting for about 35.5% of hematological admissions and 
acute leukemias were the leading cause of mortality, accounting for 78.1%of all 
hematological deaths.     
 
 Acute Leukemias  
Acute leukemias are characterized by the presence of immature white blood cells in the marrow and peripheral blood.  
There are two types of acute leukemias: 
1. Acute lymphoblastic leukemia ( ALL ) 
2. Acute myeloblastic leukemia ( AML ) 
Such a classification of acute leukemias and further sub typing is done by using


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Internal Medicine 
 
 407• Morphology of the cells 
• Immuno-phenotypic characteristics 
• Cytochemical characteristics 
Differentiation between ALL and AML is critical because the two have different  
• Natural history 
• Prognosis 
• Response to treatment 
 
A) Acute lymphoblastic leukemia (ALL) 
Is common in children:  85 % of cases of ALL occur in children, and 90 % of leukemia that occur 
in children is ALL. 
Lymphoblasts are abnormal white blood cells that are found both in the bone marrow & the peripheral blood of patients with ALL. They are characterized by
 
• Smaller size (10-15mm) than myeloblasts 
• Thin rim of dark blue cytoplasm with no granules 
• Nucleus is round or convoluted, and centrally located and has 1 or 2 nucleoli 
which are less prominent 
Morphologically ALL is categorized into 3 subtypes (FAB classification) 
1) L1 homogeneous population of small cells (childhood), a small nucleolus 
2) L2 - more heterogeneous population of larger cells (more often seen in adults) with ≥ 
1 prominent nucleoli 
3) L3 - uncommon (constituting <5% of ALL), more mature subtype, large vesicular 
nucleus with basophilic often vacuolated cytoplasm.  
Immuno phenotypic classification  of ALL  
1) Common ALL  (L1, L2) account 75% of ALL, derived from precursors of B-cell. 
2) T-ALL  (L1, L2) account for 20%of ALL: common in adolescent males, associated with 
high WBC count, anterior, mediastinal  mass and central nervous system 
involvement.


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2) T-ALL  (L1, L2) account for 20%of ALL: common in adolescent males, associated with 
high WBC count, anterior, mediastinal  mass and central nervous system 
involvement. 
3) B-cell ALL  (L 3) accounts for 5% ALL. Extramedullary presentation with metabolic 
abnormality.


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Internal Medicine 
 
 408B) Acute myeloblastic leukemia(AML) 
Myeloblasts are abnormal cells that predominantly make up AML. These cells are larger than 
lymphoblasts   and have:- 
• Lower nuclear to cytoplasmic ratio 
• Prominent multiple nucleoli 
• Auer rods (stick like structures in the cytoplasm)  in 50% of AML  
• Granules in the cytoplasm 
 
The FAB group divided AML into 8 subtypes based on 
1. Degree of differentiation 2. Maturation of predominant cells towards granulocytes, monocytes erythrocytes or 
megakaryocytes 
Subtypes of AML 
1) M
0 (also called undifferentiated AML)  
- Composed of primitive cells without cytochemical stains 
- Account for 3% of AML  
2) M 1 (AML without maturation)  
- Few if any azurophilic granules 
- Account for 20% of AML 
3) M 2 (AML with maturation)  
- Blasts with promyelocytic granules  
- Auer rods present 
- Strong avidity to perixidase and Sudan black   
- Account for  25% of AML 
4) M 3 (promyelocytic leukemia)  
- Hyper granular promyelocytes often with   
- Auer rods per cell 
5) M 4 (Acute myelomonocytic leukemia)  
- Monocytoid appearing cells in peripheral blood. 
- Strong avidity to non-specific esterase  
- account for  20% of AML 
- M 5 (acute monocytic leukemia)  
- 2 subtypes


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Internal Medicine 
 
 4096) M5a – undifferentiated M5b - differentiated with 80% promyelocytes and  monocytes                         
- Both have avidity to non specific esterase and account for 20% of AML 
7) M 6 (acute erythroleukemia)  
- Erythroblasts are more than 50% of all nucleated cells 
- Avidity to periodic acid Schiff stain 
- Account for  5% of AML 
8) M 7 (acute megakaryocytic leukemia)  
- Megakaryoblasts are more than 30% of all nucleated cells                    
- Account for 5% of AML.  
- Activity to PAS. 
Pathophysiology 
Acute leukemias are characterized by clonal proliferation of immature hematopoietic cells.  The 
most important characteristic is a defect in maturation beyond the myeloblast or promyelocyte 
level in AML, and beyond lymphoblast in ALL. Proliferation of these immature cells in the bone marrow leads to  
• Appearance of these blast cells in the ci rculation where they aren't normally seen and 
occlusion of microcirculation by blast cells (leukostasis) 
• Infiltration of the tissues i.e. lymph nodes liver, spleen, skin, gum, viscera and central 
nervous system etc - causing enlargement  of lymph nodes, liver, spleen, gum etc. 
• Accumulation of blasts in the bone marrow has two major effects on the normal blood 
cell formation (hematopoisis) causing bone marrow failure.   
o They suppress the normal hematopoisis 
o They replace the normal elements in the bone marrow


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• Accumulation of blasts in the bone marrow has two major effects on the normal blood 
cell formation (hematopoisis) causing bone marrow failure.   
o They suppress the normal hematopoisis 
o They replace the normal elements in the bone marrow  
These bone marrow changes will decrease the normal blood cells in the circulation and cause 
o Infection  - due to decreased WBC 
o Anemia - due to decreased RBC 
o Bleeding - due to decreased platelets 
Clinical Features ALL and AML share many clinical features.  In the majority of cases the initial symptoms are present for less than 3 months and are the consequence of bone marrow failure, i.e. 
• Symptoms of anemia  such as tiredness, weakness, shortness of breath on exertion 
• Recurrent infection  of any part of the body is common due to  
o Low neutrophil count in the circulation


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Internal Medicine 
 
 410o Functionally abnormal neutrophils 
o Disruption of mucosal barriers 
• Bruising and/or bleeding  related to low platelet count 
• Occasionally, lymph node enlargement  and/or symptoms relating to enlargement of 
the liver and spleen. 
• Symptoms related to hypoperfusion of the lungs and brain due to occlusion of 
microcirculation of these organs by blast cells. 
Physical findings:  but some patients may have 
• Pallor 
• Bruises, petechial hemorrhages, purpura 
• Signs of infection like fever 
• Peripheral lymphadenopathy in ALL, not common in AML 
• Enlarged liver and spleen in ALL and small percentage of AML 
• Testicular involvement in ALL (T. variant) 
• Bone pain and sternal tenderness which are due to expanding malignant cell mass, 
occur in more than half of the patients with acute leukemias. 
• Symptoms related to involvement of the c entral nervous system (meningitis, etc) and the 
kidneys. 
Laboratory Investigation 
The definitive diagnosis of acute leukemia is made on the basis of peripheral blood film and 
bone marrow aspirate examination. The following tests should be done to detect the disease & 
other associated abnormalities.    
1) Complete blood count will show 
• Hemoglobin -low 
• WBC count -often very high, but occasionally decreased or normal  
• Platelet count -low 
2) Peripheral blood film  shows characteristic leukemic cells, which are distinct from each other 
morphologically, i.e.


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Internal Medicine 
 
 411Table VI-2-1 Showing the main features of acute leukemic cells 
 
 Lymphoblast  Myeloblast  
 
Cell size  Smaller  Larger  
Nucleus shape  Round , central  Irregular, eccentric  
Nucleoli  1 or 2 in number and not prominent
 More than two & prominent  
Auer rods  absent  Present in 50%  
Cytoplasm  Dark blue rim  Pale blue, granular  
 
3) Bone marrow aspiration  is mostly done on the sternum using a special needle and a smear 
prepared and stained  with Wright stain , shows  
• Increased cellularity with abnormal lymphoid or myeloid blast cell population. 
• Replacement of the normal bone marrow elements 
  Management of acute leukemias 
A) Chemotherapeutic agents , that have the capacity to kill leukemic cells, are used to treat 
leukemia.  
Chemotherapy  of acute leukemia’s is divided in to four phases  
a. Remission induction  is characterized by intensive syst emic chemotherapy with the goal of 
reducing leukemic cell below the level of clinical detection called complete remission. 
b. Consolidation/ early  intensification  phase   
After complete remission if there is no further  treatment given, leukemia cells will expand 
and lead to relapse. In this phase intensive chemotherapy is given. 
c. Maintenance phase  here lower dose chemotherapy is  given over several years. 
d. Central nervous system prophylaxis  in this phase local chemotherapy or radiation is 
given to sites of frequent relapse like CNS. This prevents leukemic meningitis.


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d. Central nervous system prophylaxis  in this phase local chemotherapy or radiation is 
given to sites of frequent relapse like CNS. This prevents leukemic meningitis.


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Internal Medicine 
 
 412Table VI-2-3. The treatment of acute leukemias (Cytotoxic drugs & phases of treatment).  
  
Phase of treatment  ALL AML 
Remission induction  Combination of vincristine 
Prednisolone and L asparaginase Daunorubucin for 4 weeks
 Daunorubucin+ cytosine arabinoside 4weeks (called 3+7 regimen
 
Continuation/intensification phase
 Combination of 6-mercaptopurine & methotrexate+ Bone marrow transplantation
 2-3 intensive cycles of the same as above or high dose of cytosine arabinoside+ bone marrow transplantation for young patients
 
CNS prophylaxis  Radiation to the whole brain Combined with intra-thecal methotrexate (given by lumber puncture)
 No benefit because CNS relapse occurs only with systemic relapse. Therefore, it is not given. 
 
Maintenance  oral 6 -mercaptopurine &  Methotrexate
 No benefit  
 
B) Supportive treatment  is applicable for both ALL & AML  
b) For patients with severe anemia and thrombocytopenia  (especially platelet count 
below 20,000 /ML with the risk of bleeding) may be transfused with whole blood and platelet concentrates. 
c)  Infections are common in acute leukemias .  
Appropriate preventive measures  should routinely be employed to prevent infections 
in such immunocompromised patients. These include   
• Isolation of staff and visitors by the use of face masks  
• Practice careful hand washing before coming in contact with the patient  
• Advise the patient to eat only cooked foods


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in such immunocompromised patients. These include   
• Isolation of staff and visitors by the use of face masks  
• Practice careful hand washing before coming in contact with the patient  
• Advise the patient to eat only cooked foods  
When infections occur , gram negative sepsis is the commonest presentation, which 
requires prompt evaluation and empirical antibi otic treatment until definitive diagnosis is 
made by blood culture, after which the antibiotic(s) can be modified depending on the organism identified & its drug sensitivity.


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Internal Medicine 
 
 413Chronic Leukemias 
 There are two main types of chronic leukemias 
1) Chronic lymphocytic leukemia 
2) Chronic myelocytic leukemia 
 
C) Chronic lymphocytic leukemia (CLL) 
 
Definition:  
• It is an incurable disease of older people characterized by an uncontrolled proliferation 
and accumulation of mature B-lymphocytes (98% of CLL) and T-lymphocytes in rare 
instances. 
• Although, the disease remains asymptomatic in a proportion of cases; symptoms of 
anemia, infections and bleeding resulting from bone marrow failure are common in the majority of patients at presentation. 
Classification : FAB suggested 3 types of CLL 
1. Typical CLL: - where more than 95% of lymphocytes in the blood are small 
lymphocytes. 
2. Prolymphocytic CLL:-  If ≥ 51% of lymphocytes in the blood are prolymphocytes 
3. Atypical CLL  :- if < 10% of lymphocytes in the blood are small lymphocytes 
Clinical Features 
In 25% the diagnosis is made incidentally in asymptomatic individuals when WBC count is done 
for other reasons.  However, the majority will have signs and symptoms resulting from:- 
1) tissue infiltration by leukemic cells 
2) Bone marrow failure with peripheral blood cytopenias and immune suppression. 
Symptoms   
CLL is a disease of older adults and commonly present with  
• Recurrent infections resulting from neutropenia & reduced immunoglobulin levels. 
• Symptoms of anemia 
• Painless lymph node enlargement 
• Spleen and liver enlargement 
Signs 
• Anemia


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• Recurrent infections resulting from neutropenia & reduced immunoglobulin levels. 
• Symptoms of anemia 
• Painless lymph node enlargement 
• Spleen and liver enlargement 
Signs 
• Anemia 
• Enlarged lymph nodes, liver and/or spleen


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Internal Medicine 
 
 414Laboratory Investigation  
1. CBC  
• Hemoglobin  is low or normal  
• WBC count > 15,000/mm3  , of which 40% are lymphocytes, with a  minimum of 
5000/ mm3 mature lymphocytes in the circulation  
• Platelets are low or normal 
2. Bone marrow  30% of the cellular elements would be mature B cells 
3. Serum immunoglobulins  are  low or normal 
4. Coomb's test  is positive in the presence of hemolysis. 
 
Promyelocytic leukemia differs from the ty pical CLL described above in that the disease 
commonly present with 
• Massive spleen enlargement but no lymphadenopathy  
• Very high WBC count (> 200,000/L) 
• Poor response to treatment 
• The cells are B cells, but they are larger  in size and have prominent nucleoli. 
Staging of CLL 
Clinical course of the disease is variable, and prognosis is correlated directly with the stage of 
the disease.  There are two different staging classifications i.e. 
1) RAl staging classification of CLL 
Stage 0 : Lymphocytosis only (in blood and bone marrow)  
Stage I:  Lymphocytosis with lymphadenopathy  
Stage II : Lymphocytosis with liver and/or spleen enlargement 
Stage III:  Lymphocytosis with anemia (Hgb <11 gm/dl) 
Stage IV : Lymphocytosis with thrombocytopenia (platelets < 100,000/ L) 
 Lymphocytosis is defined as  WBC count > 15,000/ L, of which 40% are lymphocytes 
 
2) Binet staging classification of CLL 
 Stage A = < 3 involved lymphoid areas Hgb>10g/dl


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Stage IV : Lymphocytosis with thrombocytopenia (platelets < 100,000/ L) 
 Lymphocytosis is defined as  WBC count > 15,000/ L, of which 40% are lymphocytes 
 
2) Binet staging classification of CLL 
 Stage A = < 3 involved lymphoid areas Hgb>10g/dl 
 Stage B= >3 involved lymphoid areas Platelets < 100,000/ L  Stage C = Any number of involved Hgb < 10 g/dl and/or Platelets < 100,000/ L         lymphoid areas


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Internal Medicine 
 
 415NB: The cervical, axillary and inguinal lymph node groups (unilateral or bilateral), the spleen 
and the liver each counted as one area.  
Prognosis 
• Stage 0 and 1 CLL has good prognosis. If a patient has stage 0 disease without 
other poor prognostic factors, the median survival would be more than 10 yrs without 
treatment. 
• Stage II has Intermediate prognosis - median survival is 5 yrs 
• Stage III and IV has  worse prognosis - Median survival  is 3 years 
 
Treatment  
Patients with CLL should be referred to centers where they can be treated and followed.  
The disease may remain stable for several years without treatment. Therefore, no 
advantage in starting drugs before there is any clinical indication for treatment: 
 
Indication for initiating treatment include:  
1) Hemolytic anemia 2) Cytopenias (neutropenia, thrombocytopenia, etc) with recurrent infections, bleeding 
3) Disfiguring lymphadenopathy 4) Symptomatic organomegally 5) Marked systemic symptoms 6) Advanced disease 
 When treatment is required alkylating agents are often the drugs of choice: 
1) Chlorambucil: is given as small daily doses or larger pulse (intermittent) every 3-6 wks 
or 
2) Cyclophosphamide is also used in the same way (daily or pulses) 
3) Steroids (prednisolone) can be used in CLL if the patient develops autoimmune hemolytic anemia, autoimmune thrombocytopenia etc  
Other modalities of treatment  which are rarely employed include


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3) Steroids (prednisolone) can be used in CLL if the patient develops autoimmune hemolytic anemia, autoimmune thrombocytopenia etc  
Other modalities of treatment  which are rarely employed include 
• Combined chemotherapy (similar to ly mphoma) is used for advanced disease  
• Splenectomy/splenic irradiation 
• IV immunoglobulin for life threatening infection


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Internal Medicine 
 
 416Response to treatment can be assessed by 
• Declining WBC count 
• Increase Hgb, platelet count 
• Decrease size of Lymph nodes  
 
D) Chronic Myelocytic Leukemia (CML) 
 
Definition : It is disease of older adults and characterized by clonal expansion of hematopoitic 
cells of myliod origin, possessing Philadelphia chromosome .  It has a progressive clinical course 
with three phases starting with chronic phase and evolving to accelerated phase and then to 
blast transformation. 
 
Epidemiology 
The incidence of CML is 1.3/100,000 population /year, with men more affected than women, 
increasing slowly with age until middle forties when the incidence rises rapidly.   
In the majority of cases the etiology is unknown.  However, CML has been one of the leukemias 
observed to have an increased prevalence fo llowing atomic explosion at Hiroshima and 
Nagasaki.  
Clinical Features 
The clinical features of CML depend on the stages of the disease, and range from early 
asymptomatic phase to severe manifestations of the accelerated phase and blast transformation.  Therefore, manifestation can be described as follows:-  
1. Chronic Phase: 
• The onset is insidious and some patients can be diagnosed while asymptomatic 
during health screening visits.   
• Others may present with fatigue, anemia, night sweating, fever, weight loss and 
symptoms related to enlarged spleen i.e. left upper abdominal dull pain and early satiety.


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during health screening visits.   
• Others may present with fatigue, anemia, night sweating, fever, weight loss and 
symptoms related to enlarged spleen i.e. left upper abdominal dull pain and early satiety.   
• A few cases may show symptoms related to granulocytic or platelet dysfunction 
i.e. recurrent infections and thrombosis manifesting commonly with persistent 
painful erection of the penis (priapism) and cerebrovascular accidents.


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Internal Medicine 
 
 4172. Accelerated phase and blast transformation(or blast crisis) 
With progression of CML from chronic phase to accelerated phase and then to blast 
transformation patients will present with severe symptoms such as  
• Unexplained fever 
• Progressive weight loss 
• Bone and joint pain 
• bleeding/ thrombosis 
• Recurrent infections 
• Increasing dose requirement of the drugs used for controlling the disease  
• 10-15% of patients may present for the first time with either the accelerated phase or 
blast transformation. 
Physical examination may show 
• In the early stage 90% of or more of the cases may show  
o Moderately pale conjunctivae 
o Enlarged spleen and mild liver enlargement. 
• Late in the disease process patients may develop 
o Lymph node enlargement 
o Chloromas – leukemic deposits on the skin & 
o Tender sternum 
 
Laboratory Findings 
1) WBC count is increased of the granulocytic series with variable degrees of maturity i.e. 
mature neutrophils and band forms are seen in the peripheral blood film. Moreover immature granulocytes such as promyelocy tes, myelocytes and metamyelocytes are 
seen in the peripheral film with increased number. Some myeloblasts are also seen, and the percentage of blasts varies according to the stage of the disease, i.e.  
• Chronic phase : blasts account for < 5% of granulocytes in the blood 
• Accelerated phase : blasts account for 
≥ 15%  but < 30% of granulocytes in the 
blood


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• Chronic phase : blasts account for < 5% of granulocytes in the blood 
• Accelerated phase : blasts account for 
≥ 15%  but < 30% of granulocytes in the 
blood  
• Blast crisis:  blasts account for ≥  30% granulocytes in the blood 
Phagocytic function is normal at diagnosis and remains normal in the chronic phase. Basopilia and monocytosis are commonly observed in the accelerated phase & blast transformation.


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Internal Medicine 
 
 4182)  Patelet count  is elevated 
3)  RBC count  and hemoglobin concentrations are low, presenting with anemia 
4)  Bone marrow  aspiration: shows increased cellula rity primarily of the myeloid and 
megakaryocytic lineage, but percentage of marrow blasts remains normal or slightly 
increased   
Depending on the laboratory findings the three stages can be defined as follows:- 
Chronic Phase 
• <5% of circulating blasts 
• < 10% blasts + promyelocytes in the blood 
• Platelets are increased 
• Mild anemia 
• Increased cellularity of bone marrow with normal or increased percentage of blasts. 
Accelerated Phase 
• Worsening anemia 
• Blasts 15-30% of granulocytes (in the blood or bone marrow) 
• Blasts and promyelocytes ≥ 30% of granulocytes (in the blood or marrow) 
• Basophils ≥ 20% of granulocytes 
• Platelet counts < 100,000/L 
Blast Crisis 
• Blasts ≥ 30% of granulocytes (in the blood or marrow) 
• Hyposegmented neutrophils 
Blast cells may be   
• Myeloid in 50% (AML) 
• Lymphoid in 30% (ALL) 
• Erythroid in 10% (erythroleukemia) 
• Undifferentiated in 10% 
Treatment 
• The goal of treatment is complete molecular remission and cure (i.e. achieving 
prolonged, durable non-neoplastic and non clonal hematopoisis).   
• The treatment includes the following (used singly or in combination) 
1) Chemotherapy - hydroxyurea or busulphan - used in Ethiopia  
2) Bone marrow transplantation - the only curative treatment but not available in this 
country


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Internal Medicine 
 
 4193) Interferon  treatment  
 
References:  
1) Kasper L., Braunwald E., Harrison’s principles of Internal medicine, 16th 
Edition, Acute and chronic Myeloid leukemia, Malignancies of Lymphoid cells, 
pages 631-655. 
2) Myers R. Allen, National Medical Series for independent Study (NMS) 3rd 
edition Acute leukemia, 123-126.


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Internal Medicine 
 
 4203. Lymphomas  
 
Learning objectives : At the end of this lesson, the student will be able to:- 
1. Define lymphomas 
2. Understand the differentiating features of common lymphomas 
3. Identify clinical features of lymphomas including specific features 
4. Understand the clinical staging of lymphomas with its significance 
5. Principles of management of lymphomas 
 Definition:   Malignant transformation of cells resi ding predominantly in lymphoid tissue.  
Lymphoma is broadly classified as  
• Hodgkin’s disease 
• Non-Hodgkin’s lymphomas  
 
A. Hodgkin’s disease 
 
Epidemiology:  
• It has bimodal age incidence (20-30 years and > 50 years).  
• In developing countries young adults are commonly affected.  
• Male to female ratio = 2:1  
Clinical manifestations 
• Most patients present with non-tender asymmetrical, firm, discrete and rubbery 
enlargement of superficial nodes: Cervical (60-70%), axillary (10-15%) inguinal (6-12%). Has waxing and waning feature.  
• Mild spleenomegaly (50%), mediastinal Lym phadenopathy (6-11%) with or without plural 
effusion and superior venacaval syndrome may be present.  
• Constitutional symptoms like fever, weight loss and sweating are common in widespread 
disease. Fever is found in 30% of patients, and it described as Pel – ebsteins fever 
characterized by weeks of febrile period, interspersed by several weeks of afebrile 
period. 
• Pruritis is seen in 25%of patients


