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MEH Sem 1 > Lecture 7 (Part 1) - Vit B12 and folate > Flashcards

Lecture 7 (Part 1) - Vit B12 and folate Flashcards

1
Q

Define anaemia. List signs and symptoms.

A
  • Def: Hb conc is lower than normal range (varies w age/sex/ethnicity)
  • Symptoms: weakness, confusion, lethargy, breathlessness, headaches, angina
  • Signs: Pallor, tachycardia, increase breathing rate
  • *SPECIFIC SIGNS:
  • Iron deficiency: Koilonychia (spoon-shaped nails), Angular stomatitis (inflammation of corners of mouth)
  • Vit B12 deficiency: Glossitis (inflammation/depapillition of tongue -shiny)
  • Thalassemia: Abnormal facial bone dev. (rare)
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2
Q

How does defects in red cell metabolism result in anaemia?

A
  • G6PDH deficiency (catalyses PPP) –> X NADPH/reduced glutathione –> sus. to oxidative dmg –> random disulphide bonds –> aggregates formed–> Heinz bodies (recognised and removed)
  • Pyruvate kinase deficiency (last enzyme in glycolysis, phosphoenolpyruvate –> pyruvate), rare genetic defect
  • RBC X mitochondria, all energy from glycolysis = no P.K –> X ATP & haemolyse
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3
Q

Excessive bleeding = anaemia. What causes excessive bleeding?

A
  • Acute blood loss: injury, surgery, birth
  • Chronic NSAID usage: anti-inflammatory drug –> induce GI bleeding (inhibition of cyclooxygenase (COX) or direct cytotoxic effects on epithelium)
    [aspirin, ibuprofen, naproxen]
  • Chronic bleeding: heavy menstrual bleeding, kidney/bladder tumour (blood lost in urine), GI bleeding (ulcers/intestinal cancer)
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4
Q

What are reticulocytes? Why are they useful in evaluating anaemia?

A
  • Immature RBC (have RNA - stain blue)
  • No nucleus/mitochondria
  • Slightly larger than mature RBC –> increase MCV
  • Shows if BM is functioning properly (anaemia –> reticulocyte ⬆️, BM make more RBC)
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5
Q

Megaloblastic anaemia is an example of macrocytic anaemia. What causes megaloblastic anaemia? Briefly describe how megaloblasts form

(Macrocytic = avg. rbc bigger than normal, ⬆️MCV)

A
  • DNA synthesis affected due to retarded dev. of nucleus –> cell continues to divide (large immature nucleus) –> megaloblasts form
    [RNA and protein synthesis is normal, so cytoplasm unaffected]
    [Have hypersegmented neutrophils (>4 nuclei lobes)]
  • Caused by: vit B12/folate deficiency, drugs that interfere w DNA synthesis (anti-cancer)
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6
Q

Macronormoblastic anaemia is an example of macrocytic anaemia. What causes it?
(Macrocytic = avg. rbc bigger than normal, ⬆️MCV)

A
  • Normal dev. of cytoplasm and nucleus but erythroblasts (early dev. of RBC) larger than normal –> megaloblasts
  • Causes: liver disease, alcohol
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7
Q

Stress erythropoiesis is an example of macrocytic anaemia. What causes it?
(Macrocytic = avg. rbc bigger than normal, ⬆️MCV)

A
  • Associated w high reticulocyte count
  • High level of erythropoietin –> accelerated erythropoiesis
  • Causes: recovery from blood loss/haemolytic anaemia
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8
Q

What foods rich in folate? Where does absorption of folate usually occur and where is it stored? Function of folate is?

A
  • Green leafy veges/liver
  • Absorption in duodenum and jejunum
  • Folate –> tetrahydrofolate (FH4) by intestinal cells –> liver (storage, enough for 3-4 months requirement)
  • Function: provide carbon for other reactions + required for DNA synthesis
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9
Q

What are the causes of folate deficiency?

A
  • Poor diet
  • Increased requirement: pregnancy/HA/psoriasis
  • Disease of duodenum/jejunum (Crohn’s/coeliac)
  • Alcohol (result in poor diet and dmg to intestinal cell)
  • Drugs that inhibit dihydrofolate reductase (Methotrexate)
  • Liver disease/heart failure –> loss folate in urine
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10
Q

Symptoms of folate deficiency

A
  • Muscle weakness
  • Paraesthesia
  • Diarrhoea

(share symptoms w anaemia - breathlessness)

**Folic acid taken before conception and 12 weeks of pregnancy to prevent neural tube defects

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11
Q

What is function of Vit B12? Sources

A
  • Water sol. vit, produced by bac
  • Function:
    i) Essential cofactor for DNA synthesis
    ii) Required for normal erythropoiesis
    iii) Essential for CNS dev.
  • Sources: meat, fish, milk, cheese, eggs, yeast
    [largely from animal origin]
    **Vegan diet eat food fortified w B12 or supplements
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12
Q

Briefly desc. vit B12 absorption

HIT

A
  1. B12 from diet binds to haptocorrin
  2. Haptocorrin B12 complex digested by pancreatic protease –> B12 released binds to intrinsic factor
  3. Intrinsic factor B12 complex taken up by receptor mediated endocytosis into enterocytes (intestinal cell)
  4. Binds to transcobalamin in blood
  5. Stored in liver (3-6 year requirement)
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13
Q

What is pernicious anaemia?

A
  • Caused by absent/decreased intrinsic factor –> deplete B12
  • AI disease: Antibody block binding of B12 to IF (common) OR binding Ab prevent receptor mediated endocytosis
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14
Q

Causes of Vit B12 deficiency

A
  • Diet deficiency
  • Pernicious anaemia
  • Crohn’s
  • Chemical inactivation of B12 (frequent use of anaesthetic gas)
  • Parasitic infection
  • Drugs chelate intrinsic factor (hypercholesterolaemia drug)
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15
Q

Symptoms of Vit B12 deficiency

A

(same as anaemia)

  • diarrhoea
  • paraesthesia
  • glossitis
  • mouth ulcers
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16
Q

How does vit B12 and folate affect NS?

A
  • Folate deficiency: defect in neural tube
  • B12: demyelination (reversible)
  • Cause subacute combined degeneration of cord (irreversible): posterior and lateral degeneration of spinal cord
17
Q

Link btw B12 and folate

A
  • Folate –> tetrahydrofolate –> give up CH3 group to vit B12 –> DNA synthesis
  • transcobalamine (b12 + CH3) donates methyl group to where it can be converted HC –> methionine
18
Q

Why do B12 and folate deficiency cause megaloblastic anaemia?

A
  • Lead to thymidine deficiency –> uracil incorporated into DNA
  • DNA repair mechanisms detect and repair –> asynchronous maturation of nucleus and cytoplasm
  • Leads to large nuclei with open chromatin
19
Q

Describe megaloblastic features of blood film of patient with megaloblastic anaemia

A
  • Pancytopenia
  • Anisopoikilocytosis (vary in size & shape)
  • Hypersegmented neutrophils
  • Tear drop RBC
20
Q

Treatment for Vit B12 and folate deficiency is?

A
  • Folate: oral folic acid
  • Vit B12:
    i) for pernicious anaemia: hydroxycobalamine intramuscular (NOT ORAL)
    [beware for hypokalaemia at beginning = ⬆️K+ requirement for erythropoiesis]
    ii) for other: oral cyanocobalamine
21
Q

What happens if use blood transfusion to treat anaemia caused by vit B12 X?

A
  • Cause high output cardiac failure

- If absolutely necessary –> small vol.

22
Q

What is a direct Coombs’ test testing for?

A
  • Antibodies bound directly to the surface of red blood cells
  • used when immune-mediated haemolytic anaemia is suspected (antibody destroy RBC)
23
Q

Why in pernicious anaemia, hydroxycobalamine (B12) given intramuscularly?

A
  • decreased amount of intrinsic factor, meaning B12 cannot be absorbed into the bloodstream from the oral route, so must be administered another way.

MEH Sem 1 (18 decks)

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