haematology

Question 1

In acetaminophen (paracetamol) overdose, which toxic metabolite accumulates in the liver causing damage?

Answer 1

NAPQI

Question 2

In the treatment of acetaminophen (paracetamol) overdose, which drug can be administered to help maintain or replenish depleted liver glutathione levels?

Answer 2

Acetylcysteine

Question 3

In the treatment of acetaminophen (paracetamol) overdose, which drug can be administered to help maintain or replenish depleted liver glutathione levels?

Answer 3

Acetylcysteine

Question 4

what is a schistocyte?

Answer 4

fragmented part of a red blood cell (can be seen in aortic valve stenosis or when RBC are passing through narrowed passages)

Question 5

what are the different causes microcytic anaemia?

Answer 5

T - thalasemia
A - anaemia of chronic disease
I - iron deficiency
L - lead poisoning
S - sideroblastic anaemia

Question 6

what are the causes of normocytic anaemia?

Answer 6

A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism

Question 7

what are the 2 types of macrocytic anaemia?
what are the causes of each type of macrocytic anaemia?

Answer 7

megaloblastic or normoblastic

megaloblastic:
* B12 deficiency
* Folate deficiency

normoblastic:
* Alcohol
* Reticulocytosis (usually from haemolytic anaemia or blood loss)
* Hypothyroidism
* Liver disease
* Drugs such as azathioprine

Question 8

what triggers haemolysis in patients with G6PDH deficiency?

Answer 8

antimalarial drugs e.g. primaquine
they further deplete glutathione levels

Question 9

what is the difference between alpha and beta thalassaemia?

Answer 9

alpha thalassaemia = deletion or loss of function of one or more of the 4 alpha globin genes
beta thalassaemia = mutation in beta globin genes leading to reduction or absence of beta globin
(both result in microcytic anaemia

Question 10

1. what is hereditary haemochromatosis?
2. what happens to the excess iron?
3. how do patients present with hereditary haemochromatosis?
4. how is hereditary haemochromatosis treated?

Answer 10

1. excessive absorption of dietary iron
2. iron accumulates in organs (liver, adrenal glands, heart)
3. liver cirrhosis, adrenal insufficiency, hert failure, arthritis, diabetes
4. theraputic phlebotomy to remove excess iron

Question 11

what is the treatment for Vit B12 deficiency?

Answer 11

for pernicious anaemia: intramuscular hydroxycobalamine
other causes of B12 deficiency: oral cyanocobalamine

Question 12

what is the treatment of folate deficiency?

Answer 12

oral folic acid

Question 13

which cytokine increases production of hepcidin in liver?

Answer 13

interleukin 6 - released as a consequence of inflammatory disease
can cause anaemia of chronic disease

Question 14

what is the function of transcobalamin II?

Answer 14

binds to vit B12 once taken up by enterocytes and facilitates transport of B12 from blood into tissue

Question 15

what is the function of transcobalamin I?

Answer 15

produced by salivary glands + serves to protect Vit B12 from acid degradation in stomach

Question 16

α thalassaemia

1. what disease is caused by a defect in 1 α globin gene?
2. how severe is this disease?

Answer 16

1. silent carrier state
2. no symptoms

Question 17

α thalassaemia

1. what disease is caused by a defect in 2 α globin gene?
2. how severe is this disease?
3. how does this disease appear on blood flim?

Answer 17

1. α thalassaemia trait
2. minimal or no anaemia
3. microcytosis and hypchromia in RBC

Question 18

α thalassaemia

1. what disease is caused by a defect in 3 α globin gene?
2. how severe is this disease?
3. how does this disease appear on blood flim?

Answer 18

1. Haemoglobin H disease
2. moderately severe
3. tetrameres of β globin called HbH form resulting in microcytic, hypochromic anaemia with target cells and heinz bodies

Question 19

α thalassaemia

1. what disease is caused by a defect in 4 α globin gene?
2. how severe is this disease?
3. how does this disease appear on blood flim?

Answer 19

1. hydrops fetalis
2. severe and usually results in intrauterine death
3. all 4 α deleted and excess γ globin forms tetrameres in foetus called Hb Bart - unable to deliver oxygen to tissue

Question 20

what is hereditary eliptocytosis?

Answer 20

inherited blood disorder in which large num of RBC are eliptical in shaped
usually as a result of mutation in spectrin

Question 21

what is measured by the Coombs test?

Answer 21

determines if antibodies or complement system factors have bound directly to the surface of RBC

Question 22

1. what is apparent polycythaemia?
2. what can cause apparent polycythaemia?

Answer 22

1. absolute num of RBC is normal but there is reduced vol of plasma which presents as RBC concentration being rasied
2. obesity, smoking, drinking too much alcohol or drugs which reduce plasma vol e.g. diuretic

Question 23

what is anaemia of chronic disease?

Answer 23

sufficient iron in body but it isnt made available to bone marrow
this is because hepcidin degrades ferroportin so iron isn’t released from stores in the macrophage

Question 24

what is a leucoerythroblastic film?
what causes a leucoerythroblastic film?

Answer 24

1. spilling out of blast cells and nucleated RBC from marrow when the marrow is under stress
2. bone marrow inflitration by metastatic carcinoma or primary myelofibrosis, severe infection or septic shock

Question 25

how does sickle cell disease cause vaso-occlusive episodes?

Answer 25

1. HbS forms tetrameres under normal oxygen tension 1. HbS forms polymers under low oxygen tension 1. HbS polymers causes cells to adopt sickle shape 1. repeated sickling cycles causes irreversible sickled RBC * this causes vaso-occlusive episodes which causes stroke and acute chest syndrome

Question 26

what is feltys syndrome?

Answer 26

triad of: 1. rheumatoid arthritis 2. neutropenia 3. splenomegaly

Question 27

what is pernicious anemia?

Answer 27

decreased or absent intrinsic factor causes progressive exhaustion of B12 reserves

Question 28

how is iron absorbed from diet?

Answer 28

* haem iron is more readily absorbed than non-haem iron * non-haem iron must be reduced to Fe2+ by reductase * Fe2+ enters cell via DMT1

Question 29

how does iron exit ileum cells into blood stream?

Answer 29

ferroportin (inhibited by hepcidin)

Question 30

in what 2 forms is iron stored in the body?

Answer 30

ferritin haemosiderin

Question 31

how is iron transported around the body?

Answer 31

Fe3+ is bound to transferrin and transported around the body

Question 32

how is iron absorbed from blood into cells?

Answer 32

* Fe3+ bound to transferrin binds to transferrin receptors + enters cytosol in form of vesicle (receptor mediated endocytosis) * Fe3+ is reduced to Fe2+ * Fe2+ is transferred to cytosol via DMT1

Question 33

how is iron utilised in cells?

Answer 33

converted to ferritin for storage taken up by mitochondria to use in cytochrome enzyme exported by FPN1 back into blood

Question 34

what causes macrocytic anaemia?

Answer 34

B12 or folate deficiency liver disease alcohol excess

Question 35

what causes megaloblastic anaemia?

Answer 35

B12 deficiency or folate deficiency since they are required for DNA synthesis increased cytoplasmic:nuclear large immatured RBC with nucleus and chromatin ejected into blood stream

Question 36

1. where is folate absorbed? 2. what is folate converted to in the body? 3. what is meant by the term one carbon carrier? 4. what can folate deficiency cause?

Answer 36

1. duodenum and jujenum 2. **tetrahydrofolate (FH4)** by intestinal cells before entering the portal circulation and much of this is taken up by the liver which acts a store 3. FH4 accepts one carbon molecule from various sources and donates the carbon for various metabolic processes 4. defective DNA synthesis casues megaloblastic anaemia + in pregnancy can cause neural tube defects in foetus

Question 37

1. how is vit B12 absorbed? 2. how is vit B12 transported in body? 3. where is most vit B12 stored in body?

Answer 37

1. forms a complex with proteins called **haptocorrins**. The haptocorrin B12 complex is then digested by pancreatic proteases in the small intestine releasing the B12 which then binds to a glycoprotein called **intrinsic factor** 2. Once internalised B12 forms a complex with **transcobalamin** **II** and is released into the bloodstream for delivery to various tissues 3. liver for 3-6 years

Question 38

what is functional folate deficiency?

Answer 38

Vit B12 is required to transfer a methyl group from FH4 to homocysteine to form methionine * lack of vit B12 traps the folate in the FH4 form preventing its use in other reactions

Question 39

what are the different types of haemoglobin?

Answer 39

Hb A = most common in adults = 2α/2β Hb A2 = second most common in adults = 2α /2δ Hb F = in foetus = 2α /2γ