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Year 2 - Haem > 3 - Anaemia and polycythaemia > Flashcards

3 - Anaemia and polycythaemia Flashcards

1
Q

What is anaemia?

A

A reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender

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2
Q

What cell parameters will be reduced in anaemia?

A

Hb

RBC and Hct

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3
Q

Other than a reduction in the absolute amount of haemoglobin in the blood stream, what else could cause anaemia?

A

An increase in the plasma volume (decreases Hb concentration)

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4
Q

Why would anaemia due to increase in plasma volume only be transient in a healthy person?

A

The excess fluid would be excreted in a healthy individual

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5
Q

Broadly speaking, state four mechanisms of anaemia.

A
  • Reduced production of RBCs/Hb in the bone marrow
  • Loss of blood from the body (haemorrhage)
  • Reduced survival of red blood cells (haemolytic)
  • Pooling of red blood cells in a very large spleen
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6
Q

For each type of anaemia, state whether they are usually hypochromic, normochromic or hyperchromic.

What are the usual causes of these?

A

Microcytic – hypochromic
Normocytic – normochromic
Macrocytic - normochromic

NOTE: the cell colour helps to suggest causes
microcytic - due to lack of Hb synthesis
normochromic colour - not due to lack of Hb synthesis

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7
Q

State the common causes of microcytic anaemia.

A 
Problem with Haem synthesis
•	Iron deficiency
•	Anaemic of chronic disease
Problem with globin synthesis
•	Alpha thalassemia
•	Beta thalassemia
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8
Q

What mechanism usually causes macrocytic anaemia?

A

It usually results from abnormal haemopoiesis
(RBC precursors continue to synthesize Hb and other proteins, but they fail to divide normally)
e.g. maragloblastic erthyropoiesis

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9
Q

What is megaloblast?

A

a large, abnormally developed red blood cell typical of certain forms of anaemia, associated with a deficiency of folic acid or of vitamin B12.

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10
Q

Name 2 mechanisms of macrocytic anaemia

A
  • megaloblastic erythropoiesis (delay in maturation)

- premature release of cells from the bone marrow (will see an increase in reticulocyte count)

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11
Q

What is megaloblastic erythropoiesis?

Describe the appearance of a megaloblast.

A

Megaloblastic erythropoiesis refers to a delay in the maturation of the nucleus while the cytoplasm continued to mature and the cell continues to grow

A megaloblast is an abnormal bone marrow erythroblast
They are large and show nucleo-cytoplasmic dissociation

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12
Q

State the two most common causes of megaloblastic anaemia.

A 
B12 deficiency
Folate deficiency 
(common in the elderly)
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13
Q

State some other common causes of macrocytic anaemia.

A
  • Drugs that interfere with DNA synthesis (e.g. chemotherapy)
  • Liver disease and ethanol toxicity (most common cause)
  • Recent major blood loss (reticulocytes increased)
  • Haemolytic anaemia (reticulocytosis increases)
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14
Q

State three mechanisms of normocytic normochromic anaemia.

A
  • Recent blood loss
  • Failure to produce red blood cells
  • Pooling of red blood cells in the spleen
  • also seen in the early stages of microcytic and macrocytic anaemia
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15
Q

State five causes of normocytic normochromic anaemia.

A
  • Peptic ulcer
  • Oesophageal varices
  • Trauma
  • Failure of production of red blood cells
    • Early stages of iron deficiency and ACD
    • Renal failure
    • Bone marrow failure
    • Bone marrow infiltration
  • Hypersplenism (pooling of blood cells in an enlarged spleen)
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16
Q

Define haemolytic anaemia.

A

Anaemia resulting from shortened survival of red blood cells in the circulation

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17
Q

State two different classifications of haemolytic anaemia.

A
  • inherited - resulting from intrinsic abnormalities of the cell membrane, Hb or the enzymes in RBCs
  • acquired - resulting from extrinsic factors such as micro-organisms, chemicals or drugs

can also be described

  • intravascular- very acute damage to the red cell
  • extravascular - the spleen removes defective red cells
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18
Q

What is the hallmark feature of intravascular haemolyss?

A

Hb in the urine (red cells lyse in the circulation)

19
Q

State some inherited abnormalities that can cause haemolytic anaemia.

A

Abnormal red cell membrane
Abnormal haemoglobin
Defect in the glycolytic pathway
Defect in the enzymes of the pentose shuttle

20
Q

State some acquired abnormalities that cause haemolytic anaemia.

A

Damage to the red cell membrane
Damage to the whole red cell
Oxidant exposure

21
Q

Explain how G6PD Deficiency can cause haemolytic anaemia.

A
  • G6PD is part of the pentose phosphate pathway
  • it is the only source of reduced glutathione in RBCs.
  • RBCs are at risk of damage from oxidising free radicals except for the protective effects of G6PD (oxidants may be generated in the blood stream e.g. during infection, or may be exogenous)
  • So people with G6PD deficiency are at risk of haemolytic anaemia in states of oxidative stress
22
Q

Explain how pyruvate kinase deficiency can cause haemolytic anaemia.

A
  • Pyruvate kinase is involved in the last stage of glycolysis
  • deficiency of pyruvate kinase will result in a RBC with decreased energy
  • Because RBCs cannot synthesise ATP, cellular death occurs
23
Q

When would you suspect haemolytic anaemia?

A
  • normocytic or macrocytic anaemia
  • morphologically abnormal red cells
  • increased RBC turnover
  • increased bone marrow activity
24
Q

What does the presence of fragments in the blood film suggest?

A

This suggests that red blood cells are being broken down within the circulation (in the small circulation)

25
Q

What condition causes breakdown of red blood cells in small blood vessels?

A

Microangiopathic haemolytic anaemia

26
Q

State some important signs of haemolytic anaemia.

A

Jaundice – because of the increased break down of red blood cells there is an increase in bilirubin
(can also increase the risk of gallstones)

27
Q

State examples of inherited diseases causing haemolytic anaemia that have defects at the following sites:

a. Membrane
b. Haemoglobin
c. Glycolytic Pathway
d. Pentose Shunt

A 
a.	Membrane
Hereditary spherocytosis
b.	Haemoglobin
Sickle cell anaemia 
c.	Glycolytic Pathway
Pyruvate kinase deficiency
d.	Pentose Shunt
G6PD deficiency
28
Q

State examples of acquires disease causing haemolytic anaemia that have defects at the following sites:

a. Membrane – immune
b. Whole red cell – mechanical
c. Whole red cell – oxidant
d. Whole red cell – microbiological

A 
a.	Membrane – immune
Autoimmune haemolytic anaemia
b.	Whole red cell – mechanical
Microangiopathic haemolytic anaemia
c.	Whole red cell – oxidant
Drugs and chemicals
d.	Whole red cell – microbiological
Malaria
29
Q

What is hereditary spherocytosis?

A

haemolytic anaemia or chronic compensated haemolysis resulting from an intrinsic inherited defect of the red cell membrane.

After entering the circulation, the cells lose membrane in the cell and become spherocytic

30
Q

Describe what happens in hereditary spherocytosis when the cells enter the circulation.

A
  • After entering the circulation the cells lose membrane in the spleen and thus become spherocytic
  • As cells become more spherical, they are trapped in the spleen and are removed by splenic macrophages
31
Q

What are the features of red cells in hereditary spherocytosis?

A

They are LARGE and ROUND and have an increased MCHC

32
Q

How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis (removal of RBCs prematurely by the spleen)?

A

It increases the output of red cells leading to polychromasia and reticulocytosis

33
Q

What is an effective treatment for hereditary spherocytosis?

A

Splenectomy

34
Q

Why is a good diet important in patients with hereditary spherocytosis?

A

They have increased bone marrow activity and erythropoiesis so they need a supply of B12, folate and iron to keep producing RBCs

35
Q

What can G6PD deficiency cause?

What will be seen on a blood film during these episodes?

A

Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant

Irregularly contracted cells

36
Q

What happens to haemoglobin during episodes of severe, intravascular haemolysis?

A

It becomes denatured and forms round inclusions called Heinz bodies

NOTE: you can get more than one Heinz body per cell unlike Howell-Jolly bodies

37
Q

What causes autoimmune haemolytic anaemia?

A

production of antibodies against red cell antigens

very sudden and dramatic

38
Q

Describe how autoimmune haemolytic anaemia can lead to spherocytosis.

A

The immunoglobulin bound to the red cell is recognised by splenic macrophages, which remove parts of the cell membrane leading to spherocytosis

39
Q

State two causes of spherocytosis.

A

Hereditary spherocytosis

Autoimmune haemolytic anaemia

40
Q

Describe the diagnosis of acute haemolytic anaemia.

A
  • Finding spherocytes and an increased reticulocyte count - Detecting immunoglobulin ± complement on the red cell surface
  • Detecting antibodies to red cell antigens or other autoantibodies in the plasma
41
Q

What is the treatment for acute haemolytic anaemia?

A

Corticosteroids or other immunosuppressive agents

Splenectomy in severe cases

42
Q

What is the treatment for microangiopathic haemolytic anaemia?

A
  • removing the cause (e.g. treating sever hypertension or stopping a causative drug)
  • plasma exchange (when cause = an antibody in the plasma leading indirectly to fibrin deposition)
43
Q

What signs of a bone marrow examination would indicate megaloblastic anaemia?

A

hypersegmented neutrophils and oval macrocytes
may be seen with haemoglobin and nucleus at the late stages
chromatin not fully condensed

Year 2 - Haem (10 decks)

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