Multiple choice questions

1. Haemolytic anaemias are defined as follows:

a) Those anaemias that result from a nutritional deficiency - F
b) Those anaemias that result from bone marrow failure - F
c) Those anaemias that result from an increase in the rate of red cell destruction - T
d) Those anaemias that result from a reduction in the synthesis of normal globin chains - F
e) All of the above - F
2. With regard to hereditary haemolytic anaemias:
a) These are the result of a poor diet in childhood- F
b) They are a result of poor antenatal care - F
c) They result from intrinsic red cell defects - T
d) They may result from an environmental change -F
e) None of the above - F
3. Examples of hereditary haemolytic anaemias include the following:
a) Hereditary spherocytosis - T
b) Hereditary elliptosytosis - T
c) South East Asian ovalocytosis - T
d) Pyruvate kinase deficiency - T
e) G6PD deficiency - T
4. With regard to acquired haemolytic anaemias:
a) These are the result of an extracorpuscular change - T
b) They can result from an environmental change - T
c) These are the result of an intrinsic red cell defect - F
d) Genetic abnormalities are typical - F
e) All of the above - F
5. Examples of acquired haemolytic anaemias include the following:
a) Haemolytic transfusion reactions - T
b) Haemolytic disease of the new born - T
c) Infections such as malaria - T
d) Secondary to liver or kidney disease - T
e) Paroxysmal nocturnal haemoglobinuria - T
6. Regarding the diagnosis of acute leukaemia in general:
a) It is defined as presence of >20% blast cells in blood or bone marrow at clinical presentation
-T
b) Can be diagnosed with <20% blasts if specific leukaemia associated cytogenetic or molecular
genetic abnormalities are present - T
c) Lineage of blasts is defined by morphology, immunophenotype, cytogenetic and molecular
analysis - T
 d) Cytogenetic and molecular analysis is essential and usually performed on marrow or
peripheral blood with very high blast count - T
e) Typical myeloid immunophenotype is CD13⁺, CD33⁺,CD117⁺ and TdT⁻ - T
7. The following are recognized classes of acute myeloid leukaemia (AML):
a) AML with recurrent genetic abnormalities - T
b) AML with myelodysplasia-related changes - T
c) Therapy related myeloid neoplasms - T
d) AML, not otherwise specified - T
e) Myeloid sarcoma – T
8. The following are clinical features of AML:
a) Dominated by pattern of bone marrow failure caused by accumulation of malignant cells - T
b) Thrombocytopenia and DIC are characteristic of the promyelocytic variant of AML - T
c) Gum hypertrophy and infiltration - T
d) CNS disease -T
e) Severe anaemia - T
9. Results of investigations expected in AML include:
a) Normochromic normocytic anaemia with thrombocytopenia - T
b) Blasts on peripheral smear - T
c) Tests for DIC positive in acute promyelocytic leukaemia - T
d) Biochemical tests may show increased uric acid or LDH - T
e) Leukocytosis is usual - T
10. Some general principles of treatment include the following:
a) Central venous cannula insertion - T
b) Blood product support - T
c) Prevention of tumour lysis syndrome - T
d) Prompt treatment of fever - T
e) Maintenance of platelet count >10x10⁹/L and Hb >8g/dL -T
11. Clinical features of chronic myeloid leukaemia (CML) include the following:
a) May occur in children, neonates and elderly - T
b) Symptoms of hypermetabolism e.g. weight loss, anorexia - T
c) Massive splenomegaly - T
d) Gout or renal impairment due to hyperuricaemia - T
e) Visual disturbances and priapism - T
12. The following laboratory findings may be present in CML:
a) Leukocytosis usually >50x10⁹/L - T
b) Increased circulating basophils - T
c) Bone marrow is hypercellular with granulopoietic predominance - T
d) In 98% cases, Philadelphia chromosome on cytogenetic analysis - T
e) Presence of BCR/ABL-1 fusion gene by PCR analysis - T
13. The following treatment options are used to manage CML:
a) Chemotherapy - T
b) Radiotherapy - F
 c) Combination of chemotherapy and radiotherapy - F
d) Imatinib, designed as a specific inhibitor of the BCR/ABL-1 fusion protein - T
e) Splenectomy - F
14. The response to imatinib is monitored as follows:
a) Assessment starts with regular bone marrow analysis (3-6 months) - T
b) A complete cytogenetic response is defined as absence of Philadelphia +ve cells - T
c) By karyotypic analysis of the bone marrow together with PCR analysis for BCR/ABL-1 - T
d) Regular thyroid hormone profiles - F
e) Once complete cytogenetic response is reached, monitoring continues with PCR
quantification of BCR/ABL-1 transcripts at regular intervals - T
15. The following is true regarding the Philadelphia chromosome:
a) There is translocation of part of the short arm of chromosome 22 to the short arm of
chromosome 9 - F
b) The reciprocal translocation brings most of the ABL gene into the BCR region on
chromosome 22 - T
c) The abnormal chromosome 22 is the Philadelphia chromosome - T
d) The translocated chromosome 9 is the Philadelphia chromosome - T
e) The translocation results in a 210kDa fusion protein product derived from the BCR/ABL-1
fusion gene - T

Short answer question

A 3-month-old female child is brought to the paediatric emergency room with history of persistent
inconsolable crying whenever she’s crawling with high temperature, and recurrent cough. She is the
first-born child and the mother gives history of having a sister with sickle cell disease. On examination,
temperature is 38°C with fine crepitations on auscultation of the chest. She is moderately dehydrated
with noticeable swelling around the metacarpophalangeal joints. She has pallor of the conjunctivae and
mucous membranes. Full blood count results were as follows: WCC = 23 x 10⁹/L (4-10), HB = 5.2g/dL (13-
17), Platelets = 755 x 10⁹/L (150-400). The attending doctor suspects a genetic disorder of haemoglobin.

Q1. What is the likely diagnosis in this child? Sickle cell disease or sickle cell anaemia (2 marks)

Q2. What is the underlying genetic abnormality in the diagnosis you have made? There is a point
mutation which results in the substitution of glutamic acid for valine or adenine for thymine at the 6th
position of the beta globin gene (2 marks)

Q3. What confirmatory test should you request and what result should you expect? Haemoglobin
electrophoresis or High Performance Liquid Chromatography (HPLC): Result = HbSS (2 marks)

Q4. What complications of this condition are seen in this child? Infection; Dehydration; Vaso-occlusive
crisis; Anaemia (2 marks)
Q5. What four (4) things should the treatment aim to correct in this child? As above i.e. Infection,
dehydration, pain and anaemia (2 marks)

A23-year-old female has had a history of bleeding problems all

of her life, primarily heavy menstruation and gum bleeding. A
sister and a nuncle have similar problems. Bleeding time is
prolonged.HerPTisnormalandthePTTismildlyprolonged,butitcorr
ectswitha1:1dilutionwithnormalpooledplasma.FactorVIIIactivity
is30%(Ref50-150%).Herplateletcountiswithinreferencerange.
i)What does the PT measure?
ii)What does the PTT measure?
iii)What is your diagnosis?
iv)What test would you do to confirm your diagnosis?
v)What is the inheritance pattern of this disorder?
1) PT (Prothrombin time) measure factor VII involved in the extrinsic
pathway and factors involved in the common pathway ( factors X, V, II, I )
of the coagulation cascade. Thus PT is the time taken for blood to
coagulate following addition of thromboplatin and Ca to a sample. Normal
PT= 20-30s
2) PTT (partial thromboplastin time) measures activity of factors in the
intrinsic pathway (factors XII, XI, IX, VIII) and those of the common
pathway (factors X, V, II, I). Normal PTT is 60- 70s
3) Von willebrand disease
4) Perform a Ristocetin induced platelet aggregation. Ristocetin is an
antibiotic and in von willebrand disease it causes defective platelet
aggregation.
5) The disease show autosomal dominant pattern of inherintance. In some
cases shows incomplete dominance.
A 13-year-old male has less than 1% factor VIII activity (Ref 50-
150%) measured in plasma.
1. What condition does he have?
2. What is the genetic basis of this condition?
3. Which coagulation tests would be abnormal?
4. What would the results of WBC count, Hb, Platelets and
peripheral blood smear show?
5. If he does not receive transfusion of factor VIII, what
complication would he develop?
The same patient returns after 5 years with severe
haemorrhage into the left knee joint. A 1;1 dilution of patients
plasma with normal pooled plasma does not correct the PTT.
6. What will his response to factor VIII concentrate be?
7. If he does not respond, what complication would he have
developed?
8. What options are there for treatment?
9. What risks did these patients face prior to rigorous testing of
blood products?
10. How have the risks been averted?

1) Haemophilia A (Classic haemophilia)

2) It is a sex-linked recessive disorder
3) Partial thromboplastin time
4) WBC count should be normal, Hb should be normal, Platelet count
should be normal and peripheral blood smear should demonstrate normal
cells count and morphology.
5) Complication include Muscular hematoma, haemophiliac pseudo-
hematoma (an incapsulated hematoma that may appear like a tumor),
joint deformity and disability and rarely oropharyngeal and intracranial
bleeding.
6) The concentrated factor VIII should temporary normalize the PTT
7) The patient has developed antibodies against infused factor VIII
8) Use recombinant activated factor VIIa and activated prothrombin
complex concentrate. Also immunosuprresion therapy to reduce
antibodies against infused factors.
9) Patients where at high risk of contracting viral disease such as
hepatitis viruses
10) Use of factor VIII and purified factor VIII with heat or solvent
detergent have virtually eliminated risk of viral transmission.

A 64-year-old male presents with inguinal, axillary and cervical

lymphadenopathy. The nodes are firm and non-tender. A
biopsy of a cervical node shows a histologic pattern of nodular
aggregates of small cleaved lymphoid cells and larger cells with
open nuclear chromatin, several nucleoli, and moderate
amounts of cytoplasm. A bone marrow biopsy reveals lymphoid
aggregates of similar cells.
1.Which phenotypic markers would you test for to help with
the diagnosis?
2.Based on the morphologic findings, what test would confirm
the diagnosis, and what result would you get?
3.According to the Ann Arbor staging system, what stage of
disease is this?
4.What other test would aid in the staging process?
5.Does this patient require treatment? Why/why not?
A 39-year-old male has subarachnoid and gastro-intestinal
haemorrhage. The WCC is 75x10⁹/L, and most of the WBCs
seen on the peripheral blood smear are hypergranular
promyelocytes with numerous Auer rods. Schistocytesare seen
on the peripheral blood smear as well.
1.What is your diagnosis?
2.What karyotypic abnormality would be found on cytogenetic
analysis of bone marrow cells?
3.What coagulation disorder does this person have?
4.What laboratory tests would you perform to confirm this
coagulation disorder?
5.Which blood product(s) would you transfuse to stabilize this
patient?
1) Acute promyelocytic leukemia.
2) Cytogenetic analysis will reveal a translocation the retinoic acid
receptor (RAR) on chromosome 17 to chromosome 15 t(15:17). This
blocks maturation of cells leading to accumulation of promyelocytes.
3) Disseminated intravascular coagulation (DIC). This is due to the
presence of numerous primary granules in the promyelocytes.

4) The test to be conducted include

Blood smear. Shows signs of microangiopathic haemolytic anemia
Test for fibrin degrading products (FDP). Presence indicate
simutenous activation of thrombin and plasmin, a feature of DIC

Coagulation tests; PT, PTT, Bleeding time will all be abnormal with low
serum fibrinogen

5) Treatment will be with Fresh frozen plasma concentrate (if bleeding

predominates) or protein C and antithrombin III (if thrombosis
predominates).

A 69-year-old woman complains of back pain. A radiograph

reveals a partial collapse of T11, along with several 0.5-to 1.5-
cm lytic lesions. A bone marrow biopsy is performed and a
smear of the aspirate shows mostly plasma cells.
1.What other laboratory tests would you perform in view of the
above findings?
2.What test would confirm clonality of these plasma cells?
3.What is your diagnosis?
4.What are some of the complications of this condition? Give
two (2)
5.What are some of the treatment options for this condition?
1) The following test should be conducted

Test for paraproteinemia in serum and/or urine

Test for serum immunoglobulin free light chain

Test for serum Ca and creatinine (both increase in multiple myeloma)

Full blood count

Test for the erthyrocyte sedimentation rate

2) Serum electrophoresis will show an abnormal paraprotein in the

gamma globulin with reduced alpha and beta globulin
3) Multiple Myeloma
4) Complication of Multiple myeloma include;

Renal failure- due to recurrent infection, paraproteinemia and

hypercalcemia

Bone lesions- plasma cells activate the RANK receptor on osteoclast

leading to increased bone resorption resulting in bone pain, and
fracture.

Anemia- due to bone marrow infiltration of malignant plasma cells with

displace normal hemapoetic tissue. Other symptoms will be
neutropenia and thrombocytopenia in late stages of the disease

Frequent infection- due to paraproteinemia and neutrocytopenia.

5) Intensive therapy with chemotherapy followed with stem cell
transplantation. In the elderly use of non intensive therapy to reduce
tumour burden. Supportive therapy for renal failure, bone lesions and
hypercalcaemia and infections
A 45-year-old male experienced a gradual weight loss for
months, along with weakness, anorexia and easy fatiguability.
On physical examination, there was marked splenomegaly. A
full blood count showed Hb12.9g/dL, haematocrit0.38, MCV
92fL, platelets 410x10⁹/L and WBC count of 168x10⁹/L.
Peripheral smear showed marked leukocytosis with left shifted
granulocytes showing mostly myelocytes, metamyelocytes,
band cells and segmented neutrophils. No blasts were seen.
1.Based on these findings, what is your provisional diagnosis?
2.What test would you do to confirm the diagnosis?
3.What phase of the disease is the patient in?
4.How would you monitor for minimal residual disease in this
particular patient?
5.What is the prognosis of this disorder

1) Chronic myeloid leukemia

2) The following tests should be done;
Bone marrow biopsy ( shows a hypercellular BM with granulopoetic
predominance)
Cytogenetic analysis (shows presence of BCR-ABL1 gene)
Test for serum uric acid (normally raised CML)
3) Accelarated phase. Leukocytosis, constitutional symptoms (
weakness, anorexia and fatigue) with splenomegaly indicates the
accelerated phase.
4) Response to treatment is by karyotypic analysis of BM regularly and
PCR analysis of BCR-ABL1
5) The presence of splenomegaly, and marked leukocytosis is are poor
prognostic indicators. However the accelerated phase of the disease
responds to therapy but the response is poor.
Q1. 10 marks

Define and classify hemolytic anemias giving relevant example.

• These are anemias due to increases rate of red cell destruction

Hereditary

• Membrane defects- Hereditary spherocytosis, Hereditary Elliptocytosis

• Defective red cell Metabolism (i.e. defective enzymes)- G6PD deficiency, Pyruvate kinase
• Hemoglobinopathies- sickle cell anemia, thalassemias

Acquired

• Immune
➢ Autoimmune – warm antibody type, cold antibody type
➢ Alloimmune- hemolytic transfusion reactions, hemolytic disease of the new born,
allografts esp. marrow transplantation
➢ Drug associated (methyldopa, quinidine, penicillin) -Drug-red cell membrane complex,
Immune complex
• Red cell fragmentation syndromes- Cardiac hemolysis, arteriovenous malformation,
macroangiopathic e.g. DIC
• March hemoglobinuria
• Infections- malaria, clostridia
• Chemical and physical agents- Certain drugs e.g. dapsone and Salazopyrin, Chemical poisoning
e.g. with lead, chlorate or arsine, increased copper in blood, severe burns
• Secondary- liver and renal diseases
• Paroxysmal nocturnal hemoglobinuria

Mrs Mubitas notes

Classification

1. Site of defect (intracorpuscular or extracorpuscular)

2. Site of destruction (extravascular or intravascular hemolysis)

3. Primary or Secondary aetiology (hereditary or acquired)

4. Antibody involvement

(can either be anti-body dependent (coombs positive hemolytic anemia) e.g. alloantibodies,
autoantibodies and drug-related Abs;

or anti-body independent (coombs negative hemolytic anemia) which can be instrinsic RBC
abnormalities e.g. hemoglobinopathies like sickle cell, RBD enzyme defects like G6PD deficiency or RBC
membrane defects like Hereditary spherocytosis or extrinsic RBC mechanisms e.g. Burns,
DIC,vasculitis,intracellular infections like malaria,mechanical damage i.e. heart valve replacement,
toxins)
Q2. 10 marks

A 45 year old male experienced a gradual weight loss for months, along with weakness, anorexia, and
easy fatigability. On physical examination, there was marked splenomegaly. A full blood count showed
Hb 12.9g/dl (13-17g/dl), hematocrit 0.38 (0.35-0.52), MCV 92fL (84-99fL), platelets 410 x 109/L (150-450)
and WBC count of 168 x 109/L (4-10). Peripheral smear showed marked leukocytosis with left shifted
granulocytes showing mostly myelocytes, metamyelocytes, band cells, and segmented neutrophils. No
blasts were seen.

a) Based on these findings, what is your provisional diagnosis?

• Chronic myeloid leukemia
b) What test would do to confirm the diagnosis?
• Bone marrow biopsy ( shows a hypercellular BM with granulopoetic predominance)
• Cytogenetic analysis (shows presence of BCR-ABL1 gene)
• Test for serum uric acid (normally raised CML)
c) What is the underlying cause of the condition you have diagnosed?
• It is caused by a genetic mutation in the pluripotent stem cell
• Fusion of the of the ABL-1 gene from chromosome 9 with BCR from chromosome 22
 d) What stage of the disease is the patient in?
• Chronic stable Phase
e) How would you monitor the minimal residual disease in this particular patient?
• By Karyotypic analysis of the bone marrow together with PCR analysis for BCR-ABL transcripts
in marrow or blood.

Q3. 10 marks

A 64 year old man presents with inguinal, axillary and cervical lymphadenopathy. The nodes are firm and
non-tender. A biopsy of a cervical node shows a histologic pattern of nodular aggregates of small
cleaved lymphoid cells and larger cells with open nuclear chromatin, several nucleoli and moderate
amounts of cytoplasm. A bone marrow biopsy reviews lymphoid aggregates of similar cells.

a) What type of neoplasm does this man have?

• Lymphoma
b) Based on Morphologic findings, what further tests would you request to confirm the diagnosis?
• Immunophenotyping
• Cytogenetic and genetic analysis
c) Give two (2) tests you would perform as part of clinical staging for this disease?
• Chest x-ray
• PET/CT scan
Others
• Bone marrow aspirate
• Triphene
d) According to Ann Arbor staging system, what stage of the disease is this?
• Stage IV
e) Give two (2) subtypes of this condition
• Hodgkins Lymphoma
• Non-hodgkins Lymphoma

For Hodgkin’s
a) What type of neoplasm does this man have?
• Hodgkin’s lymphoma
b) Based on Morphologic findings, what further tests would you request to confirm the diagnosis?
• Immunophenotype and cytogenetics for CD 15 and CD 30 (which will be positive whereas
negative for the typical B-cell markers)
c) Give two (2) tests you would perform as part of clinical staging for this disease?
• Chest x-ray

PET (Positron emission tomography)/CT scan of thorax, abdomen, chest and pelvis (to detect
intrathoracic, intraabdominal or pelvic disease)
 Others
➢ MRI
➢ Bone marrow trephine
➢ Liver biopsy
d) According to Ann Arbor staging system, what stage of the disease is this?
• Stage three: because disease indicates lymph node involvement above and below the
diaphragm.
e) Give two (2) subtypes of this condition
• Nodular sclerosing
• Mixed cellularity
• Lymphocyte rich
• Lynphocyte depleted
• Nodular lymphocyte predominant (Non-Classical type)

Q4. 20 Marks

You are a new doctor in town and on your first call day a 55 year old woman presents to the emergency
room. On examination, you note that she has a low Glasgow coma scale (GCS) – 8/15 and a thread pulse.
She appears jaundiced, multiple spider naevi are present on her trunk and she has massive ascites. Her
JVP is raised and auscultation reveals 3rd and 4th heart sounds (aka a gallop rhythm).

Her husband tells you that she has been a heavy drinker with poor dietary habits and she had previously
had “liver trouble”. She had begun to vomit blood the previous day.

Blood was taken for emergency investigations which showed the following results:

Renal function tests:

Na+ 129mmols/l (135-145), K+ 4.5mmol/l (3.5-5.5), urea 7.1mmol/l (1.7- 6.7), creatinine 120µmol/l (50-
100), glucose 1.5mmol (3.9-5.6), Ammonia 240µmol/l (<40)

Acid-base: pH 7.54, pCO2 6.5kPa (4.5 to 6.1), SBC 35mmol/l (22-26)

Liver function tests (LFTs):

Total protein 80g/l (60-80), Albumin 20g/l (35-50), Total bilirubin 345 µmol/l (<17), Conj. Bilirubin 290
µmol/l (<4), ALT 60U/l (1-41), Alk. Phos. 445U/l (39-117), GGT 190U/l (7-49)

a) Give three (3) likely causes of patients low GCS (6 marks)

• Hypoxia
• hypoglycemia
• Hepatic encephalopathy
• Hypotension resulting from GI bleeding, causing poor organ perfusion
 • Intracellular dehydration in the brain
• Cerebral edema due hyperuricemia

b) What acid-base disturbance has this patient developed? And what is the most likely cause? (4
marks)
• Metabolic Alkalosis with partial respiratory compensation
• Chronic liver failure possibly due to chronic alcohol ingestion or vomiting which intern causes
the acid-bade disturbance
c) What is the most likely explanation (s) for why the total protein remains normal despite the low
levels of albumin? (4 marks)
• It’s because total protein measures not only albumin but also globulin whose production in
the case increases, so despite albumin low levels of albumin are due to decreased synthetic
function of the liver, the increase in globulins is due to portal blood shunting which results,
and GIT antigens as well as inflammation.
d) What life threatening complication may arise in this patient because of her ascites? (2 marks)
• Portopulmonary hypertension
• Hepatopulmonary syndrome
• Bacterial peritonitis
e) What underlying cardiac pathology might have developed in this patient? (2 marks)
• Right-sided heart failure
f) What x-ray finding would support your answer in ‘e’? (2 marks)
• Cardiomegaly
• Cephalization of the pulmonary vessels (redistribution of visible pulmonary vessels into upper
lung frields as pulmonary vascular volume pressures increase)
• Kerley B-lines (are horizontal lines in the lung peripheray that extend to the pleural surface.
They denote thickened, edematous interlobular septa often due to pulmonary edema)
• Pleural effusions
Q5. 30 marks

A 7 year old boy presents at UTH children’s hospital with a swollen face. The mother tells you that she
has observed that her son’s urine looks frothy. You check the child’s blood pressure, which is normal,
and you do a urinalysis that reveals protein 3+ and no blood.

a) What syndrome does the child have? (5 marks)

• Nephrotic syndrome
b) What organ has the primary pathology? (5 marks)
• Kidney
c) Which part of this organ is affected? (5 marks)
• Glomerulus
d) What is the most common/likely light microscopy appearance of this organ in this syndrome and
at this age? (5 marks)
• It appears normal on light microscopy ( most likely minimal change)
 e) What investigative modality should be used to confirm the primary pathology in the organ (5
marks)
• Electron microscopy for Kidney biopsy
(Shows diffuse effacement of podocyte foot processes when viewed with the electron microscope.)
f) How is this condition treated?
• With corticosteroids (prednisone)

Q6. 35 marks

A 21 year old HIV positive medical student presents at your clinic with a cough. She informs you that she
has taken amoxyl and erythromycin but her cough has persisted. She informs you that she also has night
sweats and has lost weight.

a) What is the most likely diagnosis? (5 marks)

• Pulmonary Tuberculosis (TB)
b) List two (2) differential diagnoses (10 marks)
• Sarcoidosis
• Aspergillosis
• Histoplasmosis
• Pneumonia
• Leprosy
c) List two (2) investigations you would order (10 marks)
• MCS for sputum (Stain with ZN)
• Mantoux tuberculin skin test
• Gene expert
d) If she died and we did a biopsy of the lungs for histology, what would we see (5 marks)
• Caseous granulomas, giant cells
e) What type of hypersensitivity is evoked? (5 marks)
• Type IV hypersensitivity

Q7. 20 marks

Write short notes on cardiomyopathies.

These are diseases that affect the heart muscle. They can either be primary which are those
principally confined to the myocardium or secondary presenting as cardiac manifestations of a
systemic disorder. Etiology is mostly idiopathic, but a number have been found to be as a
consequence of specific genetic abnormalities in cardiac energy metabolism or in structural or
contractile proteins. Based on clinical, functional and pathology there are three major patterns:
 i) Dilated Cardiomyopathy (DCM)
• An example is arrhythmogenic right ventricular cardiomyopathy
• It is the most common (90% of cases); prevalent between 20 and 50 years
• Left ventricular ejection fraction is <40%, and in end stage <25%
• Causes include:
➢ genetic (20-50%; autosomal dominant inheritance pattern; x-linked associated with
dystrophin gene mutations)
➢ Infections e.g. coxsackievirus B
➢ Chronic alcoholism or other toxic exposure e.g. doxorubicin, cobalt
➢ Peripartum cardiomyopathy
➢ Iron overload, chronic anemia, sarcoidosis
➢ Idiopathic
• Secondary Myocardial dysfunction (mimicking cardiomyopathy)
➢ Ischemic heart disease
➢ Hypertensive heart disease
➢ Vascular heart disease
➢ Congenital heart disease
• Treatment- Cardiac Transplantation is the only definite.

ii) Hypertrophic Cardiomyopathy (HCM)

• Characterized by massive myocardial hypertrophy, defective diastolic filling, and in a third of
cases ventricular outflow obstruction.
• Ventricular cavity loses its shape and appears banana-like
• Cause of sudden cardiac death in about a third of athletes
• Left ventricular ejection fraction is 50-80%
• Mechanism of heart failure - impairment of compliance (diastolic dysfunction)
• Causes – Genetic, Fiedreich ataxia, storage diseases, infants of diabetic mothers
• Mutated gene- sarcomeric proteins esp. β-myosin heavy chain
• pattern of transmission- autosomal dominant
• Secondary myocardial dysfunction- Hypertensive heart disease; aortic stenosis
• Clinical features- massive hypertrophied left ventricle paradoxically producing markedly
decreased stroke volume; exertional dyspnea

Notes on SLE

SLE is a systemic disease with protean manifestations

(Table 4–9). The morphologic changes in SLE are therefore
extremely variable and depend on the nature of the autoantibodies,
the tissue in which immune complexes deposit, and
the course and duration of disease. The most characteristic
morphologic changes result from the deposition of immune
complexes in a variety of tissues.
Blood Vessels. An acute necrotizing vasculitis affecting
small arteries and arterioles may be present in any tissue.
The arteritis is characterized by necrosis and by fibrinoid
deposits within vessel walls containing antibody, DNA, complement
fragments, and fibrinogen; a transmural and perivascular
leukocytic infiltrate is also frequently present. In
chronic stages, vessels show fibrous thickening with luminal
narrowing.
Kidneys. Kidney involvement is one of the most
important clinical features of SLE, with renal failure
being the most common cause of death. The focus here is
on glomerular pathology, although interstitial and tubular
lesions are also seen in SLE.
The pathogenesis of all forms of glomerulonephritis
in SLE involves deposition of DNA–anti-DNA complexes
within the glomeruli. These evoke an inflammatory response
that may cause proliferation of the endothelial, mesangial,
and/or epithelial cells and, in severe cases, necrosis of the
glomeruli. Although the kidney appears normal by light
microscopy in 25% to 30% of cases, almost all cases of
SLE show some renal abnormality if examined by immunofluorescence
and electron microscopy. According to the
current International Society of Nephrology/Renal Pathology
Society morphologic classification, there are six patterns
of glomerular disease in SLE (none of which is specific to the
disease): class I, minimal mesangial lupus nephritis; class II,
mesangial proliferative lupus nephritis; class III, focal lupus
nephritis; class IV, diffuse lupus nephritis; class V, membranous
lupus nephritis; and class VI, advanced sclerosing lupus
nephritis.
• Minimal mesangial lupus nephritis (class I) is rarely
encountered in renal biopsies. Immune complexes are
present in the mesangium, but there are no concomitant
structural alterations detectable by light microscopy.
• Mesangial proliferative lupus nephritis (class II)
is seen in 10% to 25% of cases and is associated with
mild clinical symptoms. Immune complexes deposit in
the mesangium, with a mild to moderate increase in the
mesangial matrix and cellularity.
• Focal lupus nephritis (class III) is seen in 20% to 35%
of cases. Lesions are visualized in fewer than half the
glomeruli, and they may be segmentally or globally distributed
within each glomerulus. Active lesions are characterized
by swelling and proliferation of endothelial and
mesangial cells, infiltration by neutrophils, and/or fibrinoid
deposits with capillary thrombi (Fig. 4–18, A). The clinical
presentation may range from only mild microscopic hematuria
and proteinuria to a more active urinary sediment
with red blood cell casts and acute, severe renal
insufficiency.
• Diffuse lupus nephritis (class IV) is the most serious
form of renal lesions in SLE and is also the most commonly
encountered in renal biopsies, occurring in 35% to 60% of
patients. It is distinguished from focal lupus nephritis (class
III) by involvement of half or more of glomeruli. Most of
the glomeruli show endothelial and mesangial proliferation,
leading to diffuse hypercellularity of these structures
(Fig. 4–18, B) and producing in some cases epithelial
crescents that fill Bowman’s space. When extensive, subendothelial
immune complexes create a circumferential
thickening of the capillary wall, resembling rigid “wire
loops” on routine light microscopy (Fig. 4–18, C). Electron
microscopy reveals prominent electron-dense subendothelial
immune complexes (between endothelium and
basement membrane) (Fig. 4–18, D), but immune complexes
are also usually present in other parts of the capillary
wall and in the mesangium. Immune complexes can
be visualized by staining with fluorescent antibodies
directed against immunoglobulins or complement, resulting
in a granular fluorescent staining pattern (Fig. 4–18, E).
In due course, glomerular injury may give rise to scarring
(glomerulosclerosis). Most affected patients have hematuria
with moderate to severe proteinuria, hypertension,
and renal insufficiency.
• Membranous lupus nephritis (class V) occurs in 10%
to 15% of cases and is the designation for glomerular
disease characterized by widespread thickening of the
capillary wall due to deposition of subepithelial immune
complexes. Membranous glomerulonephritis associatedwith SLE is very similar to that encountered in idiopathic
membranous nephropathy (Chapter 13). Thickening of
capillary walls is caused by increased deposition of basement
membrane–like material, as well as accumulation of
immune complexes. Patients with this histologic change
almost always have severe proteinuria with overt nephrotic
syndrome (Chapter 13).
• Advanced sclerosing lupus nephritis (class VI) is
characterized by complete sclerosis of greater than
90% of glomeruli and corresponds to clinical end stage
renal disease.
Skin. The skin is involved in a majority of patients; a
characteristic erythematous or maculopapular eruption over
the malar eminences and bridge of the nose (“butterfly
pattern”) is observed in approximately half of the cases.
Exposure to sunlight (UV light) exacerbates the erythema
(so-called photosensitivity), and a similar rash may be
present elsewhere on the extremities and trunk, frequently
in sun-exposed areas. Histopathologic findings include liquefactive
degeneration of the basal layer of the epidermis,
edema at the dermoepidermal junction, and mononuclear
infiltrates around blood vessels and skin appendages (Fig.
4–19, A). Immunofluorescence microscopy reveals deposition
of immunoglobulin and complement at the dermoepidermal
junction (Fig. 4–19, B); similar immunoglobulin and
complement deposits may also be present in apparently uninvolved
skin.
Joints. Joint involvement is frequent but usually is not associated
with striking anatomic changes or with joint deformity.
When present, it consists of swelling and a nonspecific mononuclear
cell infiltration in the synovial membranes. Erosion of
the membranes and destruction of articular cartilage, such as
in RA, are exceedingly rare.
CNS. Central nervous system (CNS) involvement
also is very common, with focal neurologic deficits and/or
neuropsychiatric symptoms. CNS disease often is ascribed
to vascular lesions causing ischemia or multifocal cerebral
microinfarcts. Small vessel angiopathy with noninflammatory
intimal proliferation is the most frequent pathological lesion;
frank vasculitis is uncommon. The angiopathy may result
from thrombosis caused by antiphospholipid antibodies.
Premature atherosclerosis occurs and may contribute to
CNS ischemia. Another postulated mechanism for CNS
disease is injury from antineuronal antibodies with consequent
neurologic dysfunction, but this hypothesis remains
unproved.
Other Organs. The spleen may be moderately enlarged.
Capsular fibrous thickening is common, as is follicular hyperplasia
with numerous plasma cells in the red pulp. Central
penicilliary arteries characteristically show thickening and
perivascular fibrosis, producing onion-skin lesions.
Pericardium and pleura, in particular, are serosal membranes
that show a variety of inflammatory changes in SLE
ranging (in the acute phase) from serous effusions to fibrinous
exudates that may progress to fibrous opacification in the
chronic stage.
Involvement of the heart is manifested primarily in the
form of pericarditis. Myocarditis, in the form of a nonspecific
mononuclear cell infiltrate, and valvular lesions, called
Libman-Sacks endocarditis, also occur but are less
common in the current era of aggressive corticosteroid
therapy. This nonbacterial verrucous endocarditis
takes the form of irregular, 1- to 3-mm warty deposits, seen
as distinctive lesions on either surface of the leaflets (i.e., on
the surface exposed to the forward flow of the blood or on
the underside of the leaflet) (see Chapter 10). An increasing
number of patients also show clinical and anatomic manifestations
of coronary artery disease. The basis of accelerated
atherosclerosis is not fully understood, but the process seems
to be multifactorial; certainly, immune complexes can deposit
in the coronary vasculature, leading to endothelial damage by
that pathway. Moreover, glucocorticoid treatment causes
alterations in lipid metabolism, and renal disease (common in
SLE) causes hypertension; both of these are risk factors for
atherosclerosis (Chapter 9).
Many other organs and tissues may be involved. The
changes consist essentially of acute vasculitis of the small
vessels, foci of mononuclear infiltrations, and fibrinoid deposits.
In addition, lungs may reveal interstitial fibrosis, along
with pleural inflammation; the liver shows nonspecific
inflammation of the portal tracts.