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

RBC and Hct are usually also reduced

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2
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 can decrease the haemoglobin concentration

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3
Q

Why would this type of anaemia only be transient in a healthy individual?

A

The excess fluid would be excreted in a healthy individual

For practical purposes, anaemia can therefore be regarded as a resulting from a decrease of the absolute amount of haemoglobin in the circulation

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4
Q

Broadly speaking, state four mechanisms of anaemia.

A

Reduced production of red blood cells/haemoglobin in the bone marrow
Loss of blood from the body (haemorrhage or eg into the stools)
Reduced survival of red blood cells (haemolytic)
Pooling of red blood cells in a very large spleen

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5
Q

For each type of anaemia(microcytic, normocytic and macrocytic), state whether they are usually hypochromic, normochromic or hyperchromic.

A

Microcytic – hypochromic as both are usually caused by defect in Hb synthesis
Normocytic – normochromic
Macrocytic - normochromic, macrocytosis is usually caused by other defects rather than Hb synthesis so Hb conc would be normal

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6
Q

State the common causes of microcytic anaemia.

A

Problem with Haem synthesis
 Iron deficiency
 Anaemia of chronic disease: anaemia is associated to some chronic inflammatory diseases like rheumatoid arthritis/tb
Problem with globin synthesis –thalassaemia
 Alpha thalassemia (alpha chain defect)
 Beta thalassemia (beta chain defect)

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7
Q

What mechanism usually causes macrocytic anaemia?

Name the causes of macrocytic anaemia

A

Macrocytic anaemias usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally
As a result, the red cells end up larger than normal

  1. Megaloblastic eryhropoiesis
  2. reticulocyte mechanism
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8
Q

What is megaloblastic erythropoiesis? Describe the appearance of a megaloblast.

A

Megaloblastic erythropoiesis is a mechanism for MACROCYTIC ANAEMIA.
A megaloblast is an abnormal bone marrow erythroblast

The nucleus is delayed but the rest of the cell continues to grow. Cannot produce DNA quickly enough to divide at the right time and thus grow too large before division

They are large and show nucleo-cytoplasmic dissociation (nucleus more primitive compared to the rest of the cell)

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9
Q

What is an alternative mechanism of macrocytosis?

A

Reticulocyte mechanism.– premature release of cells from the bone marrow

Reticulocytes are about 20% larger than mature red cells so reticulocytosis would increase the MCV

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10
Q

State the two most common causes of megaloblastic anaemia.

A

B12 deficiency
Folate deficiency
Drugs interfering with DNA synthesis
Liver disease and ethanol toxicity

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11
Q

State some causes for the 2 mechanisms of macrocytic anaemia:

  1. megaloblastic mechanism
  2. Reticulocyte mechanism
A
Megaloblastic:
B12 deficiency 
Folate deficiency 
Drugs that interfere with DNA synthesis (e.g. chemotherapy) 
Liver disease  
Ethanol toxicity  

Haemolytic:
Recent major blood loss with adequate iron stores (reticulocytes increased). Bone marrow tries to spit out reticulocytes to compensate for the blood loss

Haemolytic anaemia (reticulocytes increased). Breakdown of RBC causing bone marrow to spit out reticulocyte which are bigger than normal RBC, hence causing macrocytic anaemia

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12
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

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13
Q

State three causes of normocytic normochromic anaemia.

A
  1. Mechanism=Recent blood loss, caused by eg:
    Peptic ulcer
    Oesophageal varices
    Trauma

2.Mechanism=Failure of production of red blood cells, caused by:
 Early stages of iron deficiency and Anaemia of CD
 Renal failure (drop in EPO)
 Bone marrow failure (reduced no of stem cells or bone marrow suppression by cancer drugs)
 Bone marrow infiltration by eg cancer cells

  1. Mechanism= Hypersplenism –Pooling of RBC in spleen, caused by PORTAL CIRRHOSIS (cirrhosis of liver)
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14
Q

Define haemolytic anaemia.

A

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

INTRINSIC OR EXTRINSIC – HAEMOLYSIS RESULTS FROM INTRINSIC ABNORMALITY OF RBC VV

Extrinsic factors can interact with red cells that have an intrinsic abnormality that make the more susceptible

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15
Q

State two different classifications of haemolytic anaemia.

A
  1. INHERITED OR ACQUIRED
  2. INTRAVASCULAR OR EXTRAVASCULAR

Haemolysis can be inherited (resulting from abnormalities of the cell membrane, haemoglobin or the enzymes in the red blood cell)

It can be acquired usually resulting from extrinsic factors such as micro-organisms, chemicals or drugs

Haemolytic anaemia can also be described as intravascular if there is very acute damage to the red cell
It can also be classified as extravascular when the spleen removes defective red cells too quickly

often haemolysis is partly intravascular and partly extravascular

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16
Q

State some inherited abnormalities that can cause haemolytic anaemia.

A
Abnormal red cell membrane eg hereditary spherocytosis
Abnormal haemoglobin  (Sickle cell)
Defect in the glycolytic pathway  (pyruvate kinase deficiency)
Defect in the enzymes of the pentose shuttle (eg G6PD deficiency)-- ALSO VERY SUSCEPTIBLE OXIDANT DAMAGE THEREFORE LINK BETWEEN INHERIITED AND ACQUIRED
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17
Q

State some acquired abnormalities that cause haemolytic anaemia.

A

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

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18
Q

Explain how G6PD Deficiency can cause haemolytic anaemia.

A

slide 27
G6PD is part of the pentose phosphate pathway, this pathway produces a lot of NADPH which helps to REDUCE OXIDATIVE STRESS. Without this pathway, cell would be more prone to oxidative stress.

Because of the oxygen-carrying role of red blood cells, they are at constant risk of oxidant damage

So people with G6PD deficiency are at risk of haemolytic anaemia via oxidative stress

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19
Q

When would you suspect haemolytic anaemia?

A
  1. Otherwise unexplained anaemia that is normochromic and usually either normocytic or macrocytic
  2. Evidence of morphologically abnormal red cells
  3. Evidence of increased red blood cell turnover (increased bilirubin and lactate dehydrogenase, LDH is released when cells are destroyed)
  4. Evidence of increased bone marrow activity
20
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)

21
Q

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

A

Microangiopathic haemolytic anaemia

Caused by overactive coagulation system, leading to fibrin mesh formation, these are protein networks that CUT RBC into schistocytes.

22
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
The increase in bilirubin can also increase the risk of getting gallstones

23
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)--LESS COMMON
d. Pentose Shunt 
G6PD deficiency
24
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)-- LESS COMMON
d. Whole red cell – microbiological 
(Malaria)
25
Q

What is hereditary spherocytosis?

A

This is 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 spleen and become spherocytic

26
Q

What are the features of red cells in hereditary spherocytosis?

A

They are LARGE and ROUND and have an increased MCHC

Become less flexible and are prematurely removed by the spleen–Extravascular haemolysis

27
Q

How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis?

A

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

28
Q

When are spherocytes mire likely to haemolyse

What is an effective treatment for hereditary spherocytosis?

A

Spherocytes are more likely to haemolyse when osmotic pressure is reduced.

Splenectomy

29
Q

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

A

so that a secondary folic acid deficiency dos not occur

tablets of folic acid

30
Q

Describe the pattern of inheritance of G6PD deficiency.

A

Gene is on X chromosome, so affected individuals are usually hemizygous mals but occasionally homozygous females.

31
Q

What can G6PD deficiency cause?

why might G6PD deficiency occur

A

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

Broad beans, Moth balls, drugs

32
Q

What tends to appear in blood films during these episodes of severe intravascular haemolysis?

A

Irregularly contracted cells

33
Q

What happens to the haemoglobin during these episodes?

A

It becomes denatured and forms round inclusions called Heinz bodies
Heinz bodies may have a bite taken out of them by a macrophage in spleen
NOTE: you can get more than one Heinz body per cell unlike Howell-Jolly bodies

34
Q

What causes autoimmune haemolytic anaemia?

A

Results from the production of antibodies against red cell antigens

35
Q

Describe how autoimmune haemolytic anaemia can lead to spherocytosis.

A

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

Complement components can also be bound to the immunoglobulin molecule, and they are also recognised by receptors on splenic macrophages

36
Q

State two causes of spherocytosis.

A

Hereditary spherocytosis

Autoimmune haemolytic anaemia

37
Q

Describe the diagnosis of autoimmune haemolytic anaemia.

A

Finding spherocytes
Increased reticulocyte count
Detecting immunoglobulin±complement on the red cell surface
Detecting autoantibodies to red cell antigens or other autoantibodies in the plasma
slide 56

38
Q

What is the treatment for autoimmune haemolytic anaemia?

A

Corticosteroids or other immunosuppressive agents Splenectomy in severe cases

39
Q

Name one cause of reduced synthesis of haem

A

reduced iron

40
Q

Condition in which there is an inherited defect leading to a reduced synthesis of globin

A

Thalassaemia–genetic defect of globin gene

41
Q

Acute haemolysis requires what treatement

A

Blood transfusion

42
Q

How might sperocytes be detected to be removed from the circulation by spleen

A

Sperocytes are less flexible, recognition of antibody and complement on the rbc surface by splenic macrophages leads to removal from circulation

43
Q

Treatment of microangiopathic haemolytic anaemia

A

Remove cause– treat severe hypertension or stop causative drug

Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition

44
Q
SBA
A microcytic anaemia is likely to be due to
Vitamin B12 deficiency
Folic acid deficiency
Iron deficiency
Haemolysis
Acute blood loss
A

Iron deficiency

45
Q

SBA
Polycythaemia in a patient seeing his general practitioner in London because of he has noticed his urine is red is most likely to be due to
Chronic renal failure
Living at high altitude
Hypoxia from chronic obstructive pulmonary disease
Haemolysis
Renal carcinoma

A

Renal carcinoma