Macrocytic & haemolytic anaemias Flashcards
What are the three types of macrocytic anaemias? [3] and common causes
Macronormoblastic erythropoiesis: normal nucleus and cyctoplasm but cells just larger. Liver diesase, alcohol toxicity
Megaloblastic anaemias: intereference with DNA synthesis. cell division delayed and erythroblasts continue to form megaloblasts: larger red blood cells. Vitamin B12 / folate deficicient. large, immature Nucleus
(Stress erythropoiesis: condition with high recituolcyte count larger than rbc: recovery from blood loss)
Where is folate absorbed? [2]
What is main role of folate? [1]
Where is folate absorbed? [2]
Duodenum and jejunum
What is main role of folate? [1]
Key for DNA synthesis: Thymidine synthesis impaired
Folate deficiency in which populations? [5]
Symptoms for folate deficiency? [4]
Folate deficiency in which populations? [4]
Populations of alcholism (poor diet and damage to intestinal cells)
Homeless people: bad diet
People suffering from conditions which require major cellular synthesis (because folate made in DNA)
Urinary loss of folate in liver disease and heart failure
Increased requirements; pregnancy, severe skin disesase, hameolytic anaemia
Symptoms:
Those related to anaemia
Reduced sense of taste
Diarrhoea
Numbness and tingling in feet and hands
Muscle weakness
Depression
Name two roles of vitamin B12 [2]
Why do vegans need vitamin B12? [1]
Which other populations often have vit. B12 deficiency? [1]
Name two roles of vitamin B12 [2]
- *DNA synthesis** (role in folate met.)
- *CNS myelination**
Why do vegans need vitamin B12? [1]
B12 only avail. from foods of animal origin that had in them commensal bacteria
Which other populations often have vit. B12 deficiency? [1]
If have problems with vitamin B12 absorbtion
Explain mech. of vitamin B12 absorbtion
ü B12 released from food proteins by proteolysis in stomach where binds to haptocorrin
ü Haptocorrin-B12 complex digested by pancreatic proteases in small intestine releasing B12 which then binds intrinsic factor produced by gastric parietal cells.
ü Intrinsic factor–B12 complex binds to cubam receptor which mediates uptake of complex by receptor- mediated endocytosis into enterocytes of terminal ilium
ü (After lysosomal release in enterocytes, B12 exits via basolateral membrane through MDR1)
ü Binds to transcobalamin in blood and transported around bloodstream
üMajority of B12 is stored in the liver (store enough to provide B12 requirements for ~3-6 years)
Name some causes of B12 deficiency [6]
Symptoms? [6]
Name some causes of B12 deficiency [6]
- Diet deficiency
- Lack of intrinsic factor: pernicious anaemia
- Diseases of ileum (Crohns)
- Lack of transcobalmin
- Chemical inactivation (frequent use of nitrous oxide)
- parasitic infection of ileum
Symptoms:
üThose related to anaemia
üGlossitis & mouth ulcers
üDiarrhoea
üParaesthesias
üDisturbed vision
üIrritability
üMental status changes
What is pernicious anaemia caused by?
Autoimmune antibodies to parietal cells (sensitive) or IF (specific) – destroy or inactivate IF: SO:
Decreased or absent Intrinsic factor (IF) causes progressive exhaustion of B12 reserves.
Explain how B12 / folate deficiency affect the NS?
Explain how B12 / folate deficiency affect the NS?
- Folate deficiency: neural tube defects
- B12 deficiency: demylination:
i) if not treated can lead to: subacute combined degeneration of the cord - degeneration of posterior and lateral columns of spinal cord -- TEST FOR WITH ROMBERG SIGN
** KEY **
How does B12 / folate deficiency cause megaloblastic anaemia?
-
- Both B12 / folate are used in DNA synthesis, so without: nucleus and cytoplasm do not mature simultaneously:
i) cytoplasm matures normally
ii) nucleus keeps getting bigger as cell division driven by DNA synthesis
How can folate mask B12 defiency?
Elevated intake of folic acid alleviates anaemia caused by B12 deficiency by providing a continual supply of active folate (otherwise B12 needed to regenerate active folate via methionine synthase). BUT irreversible neurological sequelae B12 deficiency may still occur!
How do you diagnose megaloblastic anaemia from a PBS? [1]
What is elevated for when evaluating megaloblastic anaemia bloods? [3]
What should you also test for alongside a full blood count for megaloblastic anaemia? [2]
- Diagnostic cell on smear for megaloblastic anaemia is hyper-segmented neutrophils - one of the earliest, most sensitive and specific signs. **6 or more lobes
-**
elevated: MCV, serum ferritin (bc is a type of inflammation) & plasma lactate dehydrogenase
What should you also test for alongside a full blood count for megaloblastic anaemia? [2]
- vit. B12 levels& serum folate lvls / rbc folate levels (but Serum vitamin B12 blood test can be unreliable so repeat if borderline – a low ”normal” B12 level does not rule out B12 deficiency!
If levels indeterminate check plasma total homocysteine (tHcy) and/or plasma methylmalonic acid (MMA)
Treatment of folate deficiency?
Treatment of vitamin B12 deficiency? (For pernicious anaemia? for other causes?)
Folate: oral folic acid
B12:
- for pernicious anaemia: hydroxycobalamine IM (NOT ORAL). be aware of hypokalaemia due to increased K+ requirement as erypoesis increase back to normal
- other: Oral cyanocobalamine
What is haemolytic anaemia? [1]
What are the two types? [2]
What are the key lab findings to show haemolytic anaemia? [3]
What is haemolytic anaemia? [1]
abnormal breakdown reduces lifespan of rbc
What are the two types? [2]
- *Inherited** (defetive gene). e.g. glycolysis defect, pentose p pathway (generates NADPH - which involved in anti-oxidants for rbc), membrane potein, SCA
- *Acquired**; e.g. heat damage / mech damage / antibody damage
What are the key lab findings to show haemolytic anaemia? [3]
Raised: reticulocytes, bilirubin (breakdown of haem) & LDH
what are symptoms of haemolytic anaemia? [3]
**Will depend on time frame of haemolysis
- Jaundice:**
bc more rbc being produced, more bilirubin is made as a product of more haem breakdown. This can lead to pigment gallstones. High bilirubin causes yellowish discoloration of skin & sclera of eye. - Splenomegaly due to extramedullary hematopoiesis (“making blood” outside bone marrow) in red pulp spleen.
- (Massive sudden haemolysis e.g. from incompatible blood transfusion can cause cardiac arrest due to lack of oxygen delivery to tissues & hyperkalaemia due to release of intracellular contents)Urine dark colour due to conjugated bilirubin
Define hereditary spherocytosis
Define hereditary eliptocytosis
Define hereditary pyropoikiloctysis
# _Define hereditary spherocytosis_ **Autosomal dominant** familial condition in which there is autoantibodies produced against proteins in RBC membrane -\> contracts to sphere shape
Can still perform adequately despite reduced SA but are fragile and easily lysed. More prone to degrade when passing through vessels smaller than themselves
Spectrin defect
Define hereditary eliptocytosis
Cells eliptical not biconcave
Spectrin defect
Define hereditary pyropoikiloctysis
Severe type of heridatory eliptocytosis
Spectrin defect
Label A
Heinz Bodies
