5.3 Macrocytic Anemia Flashcards
How to differentiate btwn folate and B12 deficiency anemia?
- measure B12 levels
- measure methylmalonic acid levels (normal in folate deficiency, high in B12 deficiency b/c B12 is required in its conversion to Succinyl CoA)
“P” mnemonic of parietal cells
Parietal cells
- proton pumps
- pink color on histology
- pernicious anemia
What drug can cause folate deficiency?
Methotrexate
-inhibits DHF reductase, which converts DHF to THF
Folate deficiency
-classic populations (2) of decreased folate intake
- alcoholics
- elderly
Blood smear: you see macrocytic RBCs but no hypersegmented neutrophils. What anemia is this?
This is still macrocytic anemia, but not megaloblastic anemia (folate/B12 deficiency)
-can be caused by alcoholism, liver disease, and drugs (eg 5-FU)
B12 deficiency
-most common cause
-Pernicious anemia. Autoimmune destruction of parietal cells, which make intrinsic factor
How is body’s folate obtained?
-Diet, from green vegetables and some fruits
Macrocytic anemia
-what size RBCs
MCV >100
Small intestine:
what are the 3 sections in order?
what important nutrients related to anemia are absorbed in each?
- duodeum– Iron
- jejunum– folate
- ileum – B12
B12 deficiency anemia:
why does neuropathy occur?
B12 is required for rxn of methylmalonic acid to succinyl CoA. w/o B12, methylmalonic acid builds up in spinal cord myelin, damaging the spinal cord.
symptoms:
- poor proprioception
- poor vibration sensation
- spastic paresis
What are the 2 important reactions that Vitamin B12 is important for in the body?
why are they important?
- Transfer of methyl groups:
THF–>B12–> homocysteine (converts to methionine)
- w/o B12, THF cannot release its methyl in order to enter DNA synthesis. (causing megaloblastic anemia)
2. Methylmalonic acid –> succinyl CoA (rxn requires B12)
W/o B12, methylmalonic acid accumulates. In spinal cord myelin, this damages spinal cord (neuropathy)
Why does lack of folate or B12 create megaloblastic anemia?
Lack of either means the erythroid precursors do not divide as many times as normal, resulting in macrocytic RBCs (megaloblasts)
Megaloblastic anemia:
what do you see on blood smear?
- megaloblasts (enlarged RBCs)
- Hypersegmented neutrophils (>5 lobes) (3-5 is normal) b/c they do not divide enough times
Neutrophils with >5 lobes.
What is normal number of lobes?
Why would this happen?
Normal: 3-5 lobes
>5: hypersegmented neutrophils.
This occurs in megaloblastic anemia, in which folate/B12 deficiency means blood cells divide fewer times than normal.
Folate deficiency
-how long does it take to develop?
Within months. (Body stores of folate are minimal)
How can parasites cause megaloblastic anemia?
They can damage the ileum, where B12 is absorbed. They can also absorb the B12. Example: Fish tapeworm (diphyllobothrium latum)
How is vitamin B12 acquired in the body?
-what population is most at risk for not obtaining enough?
From animal-derived proteins in the diet.
-therefore, vegans at risk
B12 deficiency
-how long does it take to become B12 deficient by lacking it in diet? why?
Years. there are large hepatic stores of B12.
therefore B12 deficiency due to diet is rare. much less common that folate deficiency from diet
In addition to blood cells, where do you see megaloblastic change in the body in megaloblastic anemia?
Rapidly dividing epithelial cells (eg intestinal cells)
Pt with megaloblastic anemia:
-what might you see on oral exam?
why?
- glossitis (smooth tongue)–b/c nutrient deficiency means rapidly dividing cells don’t turnover as frequently.
- if B12 deficiency, tongue may also be ‘beefy red’ and sore
Pt with decreased proprioception and vibration sense, as well as spastic paresis.
-What anemia to be concerned about?
- B12 deficiency anemia (megaloblastic)
- lack of B12 results in damage to spinal cord myelin
How is dietary B12 absorbed in the body? (from mouth to intestine)
- Mouth: salivary enzymes liberate B12, which binds to R-binder (from salivary gland).
- Duodenum: pancreatic proteases detach B12 from R-binder. B12 then binds to IF, from stomach parietal cells.
- B12-IF complex is absorbed in ileum.
homocysteine:
- what do elevated levels of this increase risk of?
- what anemias are there increased homocysteine?
- increase risk of thrombosis (mech not well known)
- Megaloblastic anemia (both folate and B12)
B12 deficiency anemia:
lab findings:
- serum B12
- serum homocysteine
- methylmalonic acid
- low
- high (no B12 to receive methyl from)
- high (no B12 to convert to succinyl CoA to prevent neuropathy)
What is the most common cause of macrocytic anemia
folate deficiency
What are the biochem reactions to know with folate and B12 in megaloblastic anemia?
THF–>B12–>Methionine (from homocysteine)
- Folate enters body as THF and is immediately methylated.
- In order for THF to enter DNA synthesis, it must donate its methyl to B12.
- B12 then donates its methyl to Homocysteine, turning homocysteine into Methionine (which can donate its methyl as well).
Where is dietary folate absorbed?
Jejunum
Folate deficiency
-classic causes (3) resulting from increased folate demand
- pregnancy
- cancer
- hemolytic anemia
Methotrexate:
-what anemia is this assoc with
-it can cause folate deficiency anemia (megaloblastic) since it inhibits DHF reductase (converts DHF to THF, which is used in DNA synthesis)
Folate deficiency
lab findings:
- serum folate
- serum homocysteine
- methylmalonic acid
- low
- high (b/c no methyl donated to homocysteine)
- normal (high in B12 deficiency)
methylmalonic acid –> succinyl CoA (requires B12 for reaction)
B12 deficiency
-causes (4)
- Pernicious anemia (most common)–autoimmune of parietal cells
- Pancreatic insufficiency (lack of proteases to detach B12 from R-binder)
- Damage to ileum (eg Crohn’s or fish tapeworm)
- Dietary deficiency (rare, except in strict vegans)
Folate deficiency:
-3 categories of causes
- Dietary deficiency (alcoholics, elderly)
- increased folate demand (pregnancy, cancer, hemolytic anemia)
- folate antagonists (methotrexate, inhibits DHF reductase)
Macrocytic anemia vs megaloblastic anemia
-what’s the difference
- megaloblastic anemia (From folate or B12 defiency) is the most common cause of macrocytic anemia
- Other causes of macrocytic anemia include:
1. alcoholism
2. liver disease
3. drugs (eg 5-FU)
Pt with decreased pancreatic function. What anemia to be concerned about?
B12 deficiency anemia (megaloblastic)
-loss of pancreatic proteases to detach B12 from R-binder
Pt ingests fish tapeworm. What anemia to be concerned about?
B12 deficiency anemia (parasites like this absorb B12 and also damage ileum, where B12 is absorbed)
cobalamin
Vitamin B12, (another name)
Causes of macrocytic anemia
- 2 most common causes
- 3 other causes
Megaloblastic anemia
- folate deficiency
- B12 deficiency
Other:
- alcoholism
- liver disease
- drugs (eg 5-FU)
