haematology Flashcards
In acetaminophen (paracetamol) overdose, which toxic metabolite accumulates in the liver causing damage?
NAPQI
In the treatment of acetaminophen (paracetamol) overdose, which drug can be administered to help maintain or replenish depleted liver glutathione levels?
Acetylcysteine
In the treatment of acetaminophen (paracetamol) overdose, which drug can be administered to help maintain or replenish depleted liver glutathione levels?
Acetylcysteine
what is a schistocyte?
fragmented part of a red blood cell (can be seen in aortic valve stenosis or when RBC are passing through narrowed passages)
what are the different causes microcytic anaemia?
T - thalasemia
A - anaemia of chronic disease
I - iron deficiency
L - lead poisoning
S - sideroblastic anaemia
what are the causes of normocytic anaemia?
A – Acute blood loss
A – Anaemia of Chronic Disease
A – Aplastic Anaemia
H – Haemolytic Anaemia
H – Hypothyroidism
what are the 2 types of macrocytic anaemia?
what are the causes of each type of macrocytic anaemia?
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
what triggers haemolysis in patients with G6PDH deficiency?
antimalarial drugs e.g. primaquine
they further deplete glutathione levels
what is the difference between alpha and beta thalassaemia?
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
- what is hereditary haemochromatosis?
- what happens to the excess iron?
- how do patients present with hereditary haemochromatosis?
- how is hereditary haemochromatosis treated?
- excessive absorption of dietary iron
- iron accumulates in organs (liver, adrenal glands, heart)
- liver cirrhosis, adrenal insufficiency, hert failure, arthritis, diabetes
- theraputic phlebotomy to remove excess iron
what is the treatment for Vit B12 deficiency?
for pernicious anaemia: intramuscular hydroxycobalamine
other causes of B12 deficiency: oral cyanocobalamine
what is the treatment of folate deficiency?
oral folic acid
which cytokine increases production of hepcidin in liver?
interleukin 6 - released as a consequence of inflammatory disease
can cause anaemia of chronic disease
what is the function of transcobalamin II?
binds to vit B12 once taken up by enterocytes and facilitates transport of B12 from blood into tissue
what is the function of transcobalamin I?
produced by salivary glands + serves to protect Vit B12 from acid degradation in stomach
α thalassaemia
- what disease is caused by a defect in 1 α globin gene?
- how severe is this disease?
- silent carrier state
- no symptoms
α thalassaemia
- what disease is caused by a defect in 2 α globin gene?
- how severe is this disease?
- how does this disease appear on blood flim?
- α thalassaemia trait
- minimal or no anaemia
- microcytosis and hypchromia in RBC
α thalassaemia
- what disease is caused by a defect in 3 α globin gene?
- how severe is this disease?
- how does this disease appear on blood flim?
- Haemoglobin H disease
- moderately severe
- tetrameres of β globin called HbH form resulting in microcytic, hypochromic anaemia with target cells and heinz bodies
α thalassaemia
- what disease is caused by a defect in 4 α globin gene?
- how severe is this disease?
- how does this disease appear on blood flim?
- hydrops fetalis
- severe and usually results in intrauterine death
- all 4 α deleted and excess γ globin forms tetrameres in foetus called Hb Bart - unable to deliver oxygen to tissue
what is hereditary eliptocytosis?
inherited blood disorder in which large num of RBC are eliptical in shaped
usually as a result of mutation in spectrin
what is measured by the Coombs test?
determines if antibodies or complement system factors have bound directly to the surface of RBC
- what is apparent polycythaemia?
- what can cause apparent polycythaemia?
- absolute num of RBC is normal but there is reduced vol of plasma which presents as RBC concentration being rasied
- obesity, smoking, drinking too much alcohol or drugs which reduce plasma vol e.g. diuretic
what is anaemia of chronic disease?
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
what is a leucoerythroblastic film?
what causes a leucoerythroblastic film?
- spilling out of blast cells and nucleated RBC from marrow when the marrow is under stress
- bone marrow inflitration by metastatic carcinoma or primary myelofibrosis, severe infection or septic shock
how does sickle cell disease cause vaso-occlusive episodes?
- HbS forms tetrameres under normal oxygen tension
- HbS forms polymers under low oxygen tension
- HbS polymers causes cells to adopt sickle shape
- repeated sickling cycles causes irreversible sickled RBC
* this causes vaso-occlusive episodes which causes stroke and acute chest syndrome
what is feltys syndrome?
triad of:
1. rheumatoid arthritis
2. neutropenia
3. splenomegaly
what is pernicious anemia?
decreased or absent intrinsic factor causes progressive exhaustion of B12 reserves
how is iron absorbed from diet?
- 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
how does iron exit ileum cells into blood stream?
ferroportin
(inhibited by hepcidin)
in what 2 forms is iron stored in the body?
ferritin
haemosiderin
how is iron transported around the body?
Fe3+ is bound to transferrin and transported around the body
how is iron absorbed from blood into cells?
- 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
how is iron utilised in cells?
converted to ferritin for storage
taken up by mitochondria to use in cytochrome enzyme
exported by FPN1 back into blood
what causes macrocytic anaemia?
B12 or folate deficiency
liver disease
alcohol excess
what causes megaloblastic anaemia?
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
- where is folate absorbed?
- what is folate converted to in the body?
- what is meant by the term one carbon carrier?
- what can folate deficiency cause?
- duodenum and jujenum
- tetrahydrofolate (FH4) by intestinal cells before entering the portal circulation and much of this is taken up by the liver which acts a store
- FH4 accepts one carbon molecule from various sources and donates the carbon for various metabolic processes
- defective DNA synthesis casues megaloblastic anaemia + in pregnancy can cause neural tube defects in foetus
- how is vit B12 absorbed?
- how is vit B12 transported in body?
- where is most vit B12 stored in body?
- 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
- Once internalised B12 forms a complex with transcobalamin II and is released into the bloodstream for delivery to various tissues
- liver for 3-6 years
what is functional folate deficiency?
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
what are the different types of haemoglobin?
Hb A = most common in adults = 2α/2β
Hb A2 = second most common in adults = 2α /2δ
Hb F = in foetus = 2α /2γ
