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ACEM Primary Written > Haematology: Pathology - Anaemia > Flashcards

Haematology: Pathology - Anaemia Flashcards

1
Q

Three broad causes of anaemia

A
  1. Blood loss
  2. Haemolysis
  3. Diminished erythropoiesis
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1
Q

Eight broad causes of haemolysis and give a specific example for each

A
  1. Inherited genetic defects: e.g. thalassaemia
  2. Acquired genetic defects: e.g. paroxysmal nocturnal haemoglobinuria
  3. Antibody-mediated destruction: e.g. transfusion reaction
  4. Mechanical trauma: e.g. DIC
  5. Infections of RBCs: e.g. malaria
  6. Toxins/chemical injury: e.g. clostridial sepsis
  7. Membrane lipid abnormalities: e.g. severe hepatocellular liver disease
  8. Sequestration: e.g. hypersplenism
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2
Q

Nine broad causes of haemolysis and give a specific example for each

A
  1. Inherited genetic defects: e.g. Fanconi anaemia
  2. Nutritional deficiencies: e.g. iron deficiency
  3. EPO deficiency: e.g. renal failure
  4. Immune-mediated injury of progenitors: e.g. aplastic anaemia
  5. Inflammation-mediated iron sequestration: e.g. anaemia of chronic disease
  6. Primary haematopoietic neoplasms: e.g. acute leukaemia, myelodysplasia, myeloproliferative disorders
  7. Space-occupying marrow lesions: e.g. metastatic neoplasms
  8. Infections of red cell progenitors: e.g. parvovirus B19
  9. Unknown mechanisms: e.g. hepatocellular liver disease
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3
Q

Seven useful red cell indices in diagnosis of anaemia

A
  1. Haematocrit: ratio of PRBCs to total blood volume
  2. Hb concentration
  3. MCV: average RBC volume
  4. MCH: average Hb mass per RBC
  5. MCHC: average Hb concentration in given volume of PRBCs (g/dL)
  6. RDW: coefficient of variation of RBC volume
  7. RCC: reticulocyte count
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4
Q

Where does RBC destruction take place in most haemolytic anaemias?

A

Extravascular haemolysis: within phagocytes in the spleen, liver and bone marrow

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5
Q

Contrast the clinical features of extravascular vs intravascular haemolysis

A

Extravascular:
1. Anaemia
2. Splenomegaly
3. Jaundice

Intravascular:
1. Anaemia
2. Haemoglobinaemia
3. Haemoglobinuria
4. Haemosiderinuria
5. Jaundice

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6
Q

What changes in RBC structure/function typically cause extravascular haemolysis?

A

Usually due to reduction in RBC deformability (less able to navigate the splenic sinusoids successfully, become sequestered and get phagocytosed)

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7
Q

Four causes of intravascular haemolysis and give a specific example for each

A
  1. Mechanical injury (e.g. due to cardiac valves, microangiopathy, repetitive physical trauma)
  2. Complement fixation (e.g. transfusion reaction)
  3. Intracellular parasites (e.g. malaria)
  4. Exogenous toxic factors (e.g. Clostridial sepsis)
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8
Q

Describe six changes seen in laboratory values in anaemia caused by acute blood loss, and the pathogenesis of each

A
  1. Leukocytosis: initially, due to hypotension causing increased adrenergic hormone release which stimulates granulocyte mobilisation
  2. Normochromic normocytic anaemia: initially
  3. Reticulocytosis: after 5-7 days due to increased marrow production
  4. Thrombocytosis: due to increased platelet production
  5. Decreased haematocrit: initially, due to haemodilution (rapid restoration of blood volume by shifting water from interstitial compartments)
  6. May see iron deficiency if blood is lost into gut or outside the body
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9
Q

Inheritance pattern of hereditary spherocytosis

A

AD (75%)
Compound heterozygosity (25%)

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10
Q

Morphologic findings on peripheral smear in hereditary spherocytosis

A

Spherocytosis: abnormally small, hyperchromic RBCs

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11
Q

Is spherocytosis a finding specific to hereditary spherocytosis?

A

No, can also be caused by autoimmune haemolytic anaemias

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12
Q

Morphologic features of haemolytic anaemias

A
  1. Increased marrow normoblasts
  2. Prominent reticulocytosis on peripheral smear
  3. Haemosiderosis (most pronounced in liver, spleen and marrow)
  4. Extramedullary haematopoiesis in severe anaemia (marrow erythroid hyperplasia)
  5. Cholelithiasis if chronic
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13
Q

MCHC in hereditary spherocytosis

A

Increased due to cellular dehydration caused by K+ and H2O loss

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14
Q

What is an aplastic crisis? What is a haemolytic crisis?

A

Event triggered by acute parvovirus infection in hereditary spherocytosis: parvovirus infects and kills all RBC progenitors, causing RBC production to cease until effective immune response commences in 1-2 weeks
HS RBCs have reduced lifespan compared with normal RBCs so there is sudden worsening of anaemia and transfusions may be required temporarily

Haemolytic crises are caused by intercurrent events which lead to increased splenic destruction of RBCs (e.g. infectious mononucleosis)

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15
Q

Inheritance of G6PD

A

X-linked recessive (men at higher risk)

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16
Q

Which three inherited haemolytic anaemias confer protection against malaria?

A
  1. G6PD deficiency
  2. Sickle cell trait
  3. Thalassaemia heterozygotes
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17
Q

What causes the episodic haemolysis characteristic of G6PD deficiency?

A

Exposures that generate oxidative stress:
1. Infection (e.g. viral hepatitis, pneumonia, typhoid)
2. Drugs (e.g. antimalarials, sulfonamides)
3. Certain foods (e.g. fava beans)

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18
Q

Describe the pathogenesis of haemolytic disease due to G6PD deficiency

A

Reduced ability of RBCs to protect against oxidative injuries

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19
Q

Morphologic features of G6PD deficiency

A
  1. Heinz bodies
  2. Bite cells
  3. Spherocytes
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20
Q

Mutation in sickle cell disease

A

Point mutation in B-globin

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21
Q

Pathogenesis of sickle cell disease

A

HbS molecules (with abnormal B-globin) undergo polymerisation when deoxygenated
Aggregated HbS molecules assemble into need-like fibres and produce distorted sickle shape
Increased viscosity leads to chronic haemolysis, microvascular occlusion, and tissue downstream damage

22
Q

Morphologic features of sickle cell disease

A
  1. Irreversibly sickled cells
  2. Reticulocytosis
  3. Target cells (dehydrated RBCs)
  4. Howell-Jolly bodies
  5. Erythroid hyperplasia in marrow
  6. Autosplenectomy due to splenic infarction, fibrosis and shrinkage as a result of chronic erythrostasis
23
Q

Three types of crises seen in sickle cell disease

A
  1. Vaso-occlusive crises (pain crises): due to hypoxic injury and infarction, may be triggered by insult (e.g. infection, dehydration, acidosis), includes acute chest syndrome (pulmonary inflammation)
  2. Sequestration crises: rapid splenic enlargement, hypovolaemia and shock in children
  3. Aplastic crises: triggered by parvovirus B19
24
Q

What are thalassaemias? What causes alpha and beta thalassaaemias?

A

Syndromes caused by inherited mutations that decreased synthesis of HbA

Alpha: deficient synthesis of alpha chains
Beta: deficient synthesis of beta chains

Haematologic consequences caused both by haemoglobin deficiency and relative excess of other globin chain

25
Q

What is B-thalassaemia major vs minor?

A

B-thalassaemia major: two B-thalassaemia alleles, causing severe transfusion-dependent anaemia
B-thalassaemia minor: heterozygotes with one B-thalassaemia gene and one normal gene, causing mild asymptomatic microcytic anaemia

26
Q

Seven morphologic features of B-thalassaemia

A
  1. Marked variation in RBC size (anisocytosis; high RDW)
  2. Marked variation in RBC shape (poikilocytosis)
  3. Microcytic, hypochromic RBCs (low MCV and MCH)
  4. Target cells
  5. Hepatosplenomegaly
  6. Existing bone erosion and new bone formation (radiological “crew-cut” appearance)
  7. Haemosiderosis and secondary haemochromatosis
27
Q

Four types of a-thalassaemias, their respective genotypes, and their clinical features

A
  1. Silent carrier: -/a a/a, asymptomatic
  2. a-thalassaemia trait: -/- a/a or -/a -/a, asymptomatic (like B-thalassaemia minor)
  3. HbH disease: -/- -/a, severe (resembling B-thalassaemia intermedia)
  4. Hydrops foetalis: -/- -/-, lethal in utero without transfusion
28
Q

How are immunohaemolytic anaemias diagnosed?

A

Direct Coombs: patient’s RBCs are mixed with sera containing Abs specific for human Ig or complement
Indirect Coombs: patient’s serum is tested for its ability to agglutinate RBCs bearing particular defined Ags

29
Q

Three types of immunohaemolytic anaemias. What Ab are seen in each?

A
  1. Warm Ab type: IgG Ab active at 37 degrees
  2. Cold agglutinin type: IgM Ab active below 37 degrees
  3. Cold haemolysin type: IgG Ab active below 37 degrees
30
Q

Morphologic features seen in haemolytic anaemia resulting from trauma to RBCs

A
  1. Schistocytes (RBC fragments)
  2. Burr cells
  3. Helmet cells
  4. Triangle cells
31
Q

Three broad causes of megaloblastic anaemias

A
  1. B12 deficiency
  2. Folic acid deficiency
  3. Metabolic inhibitors of DNA syntehesis and/or folate metabolism (e.g. methotrexate)
32
Q

Two broad causes of B12 deficiency

A
  1. Decreased intake (dietary)
  2. Impaired absorption
33
Q

Five causes of impaired B12 absorption

A
  1. Intrinsic factor deficiency (e.g. pernicious anaemia, gastrectomy)
  2. Malabsorption
  3. Diffuse intestinal disease (e.g. lymphoma, systemic sclerosis)
  4. Ileal resection, ileitis
  5. Bacterial overgrowth in blind loops and diverticula of bowel
34
Q

Five broad causes of folic acid deficiency and examples of each

A
  1. Decreased intake: e.g. dietary, alcoholism
  2. Impaired absorption: e.g. malabsorption, intestinal disease, OCP
  3. Increased loss: e.g. haemodialysis
  4. Increased requirement: e.g. pregnancy, neoplasm
  5. Impaired utilisation: e.g. folic acid antagonists
35
Q

Morphologic features of megaloblastic anaemia

A
  1. Macro-ovalocytes
  2. Anisocytosis (increased RDW)
  3. Poikilocytosis (variation in RBC shape)
  4. Low reticulocytes
  5. Macropolymorphonuclear hypersegmented neutrophils
  6. Megaloblastic changes at all stages of erythroid development including giant metamyelocytes and band forms, and large megakaryocytes
  7. Marrow erythroid hyperplasia
  8. Pancytopenia
36
Q

Pathogenesis of megaloblastic anaemias

A

Impaired DNA synthesis leading to distinctive morphologic changes

37
Q

Main metabolic role of B12/folate

A

Coenzymes required for synthesis of the DNA nucleoside thymidine

38
Q

What is pernicious anaemia?

A

Form of megaloblastic anaemia caused by chronic atrophic autoimmune gastritis which results in loss of parietal cells and therefore failure of intrinsic factor production

39
Q

Describe the normal metabolism of B12

A

Humans totally dependent on dietary cobalamin
Freed from binding proteins in food via action of pepsin in the stomach, then binds to salivary protein (cobalophilins)
In duodenum it is released from cobalophilins by the action of pancreatic proteases and associates with intrinsic factor
Transported to ileum and endocytosed by ileal enterocytes that express intrinsic factor receptors
Stored intrahepatically (sufficient to last for several years)

40
Q

Why can pernicious anaemia be treated with high doses of oral vitamin B12?

A

There is an alternative non-IF and non-terminal-ileum dependent absorption pathway
Up to 1% of oral dose can be absorbed via this pathway

41
Q

Morphologic changes seen in pernicious anaemia

A
  1. Atrophy of fundic glands: reduced chief and virtually absent parietal ccells
  2. Intestinalisation of gastric epithelium: glandular lining replaced by mucus-secreting goblet cells similar to large intestine lining (metaplastic process)
  3. Atrophic glossitis
  4. Central nervous system lesions: includes demyelination of spinal cord (may cause spastic paraparesis, sensory ataxia, and severe lower limb paraesthesias)
42
Q

What is the most common nutritional deficiency in the world?

A

Iron deficiency

43
Q

Describe the typical distribution of iron in the body

A

Functional: 80% in haemoglobin, rest in myoglobin and iron-containing enzymes (e.g. catalase)
Storage: haemosiderin and ferritin

44
Q

What % of total body iron is stored as haemosiderin and ferritin?

A

15-20%

45
Q

How much haemosiderin is found in the body in normal vs iron-overloaded states?

A

Normally trace amounts of haemosiderin
Most iron stored in haemosiderin in iron overload

46
Q

How is iron excreted?

A

Via shedding of mucosal and skin epithelial cells only

47
Q

What regulates iron absorption? How is this achieved?

A

Hepcidin (circulating peptide released from the liver)
Hepcidin inhibits iron transfer from enterocyte to plasma: as hepcidin levels rise, iron is trapped within duodenal cells and lose when cells are sloughed
Low hepcidin results in increased iron absorption and vice versa

48
Q

How is iron transported? What is the typical saturation of this iron-binding transport protein?

A

Transferrin
Typically 1/3 saturated with iron in normal individuals

49
Q

Four broad categories of causes of iron deficiency, with an example of each

A
  1. Decreased intake: e.g. in infants (low iron content in breastmilk)
  2. Impaired absorption: e.g. Coeliac disease
  3. Increased requirement: e.g. pregnancy
  4. Chronic blood loss: e.g. GI bleeding
50
Q

Morphologic features of iron deficiency anaemia

A
  1. Microcytic hypochromic anaemia
  2. Poikilocytosis with pencil cells
51
Q

Laboratory findings in iron deficiency anaemia

A
  1. Decreased Hb
  2. Decreased haematocrit
  3. Decreased MCH (hypochromia)
  4. Decreased MCV (microcytosis)
  5. Poikilocytosis (variation in RBC shape)
  6. Low serum iron and ferritin
  7. High TIBC and elevated transferrin
  8. Reduced transferrin saturation
52
Q

Three causes of anaemia of chronic disease

A
  1. Chronic microbial infections (e.g. OM, IE, lung abscess)
  2. Chronic immune disorders (e.g. RA)
  3. Neoplasms
53
Q

Laboratory findings (iron studies) in anaemia of chronic disease. What is the pathogenesis of these changes?

A
  1. Decreased serum iron
  2. Decreased iron binding capacity
  3. High ferritin

This is despite abundant stored iron in tissue macrophages, and occurs as a result of increased hepcidin due to action of inflammatory mediators like IL-6 (hepcidin reduces transfer of iron from storage pool to functional pool)

ACEM Primary Written (150 decks)

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