Ch5 - 3) Macrocytic anemia Flashcards
What is Macrocytic Anemia?
Anemia with MCV > 100 most commonly due to folate or vitamin B12 deficiency (megaloblastic anemia)
What are folate and vitamin B12 are necessary for?
synthesis of DNA precursors,
What does folate circulates in the serum as?
methyltetrahydrofolate (methyl THF);
What happens to methyl-THF?
removal of the methyl group allows for participation in the synthesis of DNA precursors.
What happens to the methyl group from methyl THF?
It is transferred to vitamin B12 (cobalamin),
What does Vitamin B12 do with the methyl it receives from methyl THF?
B12 then transfers the methyl to homocysteine, producing methionine.
Lack of folate or vitamin B12 does what?
impairs synthesis of DNA precursors,
What does impaired division and enlargement of RBC precursors lead to?
Megaloblastic anemia
What does impaired division of granulocytic precursors lead to?
hypersegmented neutrophils
Where is megaloblastic change also seen?
in rapidly-dividing (e.g., intestinal) epithelial cells.
What are some other causes of macrocytic anemia (without megaloblastic change)?
alcoholism, liver disease, and drugs (e.g., 5-FU).
Where is dietary folate obtained?
from green vegetables and some fruits
Where is dietary folate absorbed?
in the jejunum
How fast does folate deficiency develop?
within months, as body stores are minimal
What are some causes of folate deficiency?
1) poor diet. 2) increased demand 3) folate antagonists
What are some examples of poor diet leading to folate deficiency?
Seen in alcoholics and elderly
What are some examples of increased demand leading to folate deficiency?
pregnancy, cancer, and hemolytic anemia
What are the clinical and laboratory findings?
- Macrocytic RBCs and hypersegmented neutrophils (> 5 lobes. Fig. 5.5) 2. Glossitis 3. decreased serum folate 4. increased serum homocysteine (increases risk for thrombosis) 5. Normal methylmalonic acid
What is dietary vitamin B12 complexed to?
animal-derived proteins
What liberates Vitamin B12 that is complexed to animal derived protein?
salivary gland enzymes (e.g., amylase) liberate vitamin B12
After Vit B12 reacts with salivary gland enzymes what happens?
It is bound by R-binder (also from the salivary gland) and carried through the stomach.
What happens to Vit B12 after its bound to R binder?
Pancreatic proteases in the duodenum detach vitamin B12 from R-binder
After Vitamin B12 is detached from R binder, what happens?
It binds intrinsic factor (made by gastric parietal cells) in the small bowel;
Where is the intrinsic factor-vitamin B12 complex absorbed?
in the ileum
How common is vitamin B12 deficiency?
it is less common than folate deficiency and takes years to develop due to large hepatic stores of vitamin B12
Why does it take years for Vitamin B12 deficiency to develop?
Due to large hepatic stores of Vitamin B12
What is the most common cause of vitamin B12 deficiency?
pernicious anemia
What is pernicious anemia?
autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency
What are some other causes of vitamin B12 deficiency?
include pancreatic insufficiency and damage to the terminal ileum (e.g., Crohn disease or Diphyllobothrium latum - fish tapeworm); dietary deficiency is rare, except in vegans.
What are the clinical and laboratory findings for Vitamin B12 deficiency?
- Macrocytic RBCs with hypersegmented neutrophils, 2. Glossitis, 3. Subacute combined degeneration of the spinal cord 4. decreased serum vitamin B12. 5. increased serum homocysteine 6. increased methylmalonic acid
How does vitamin B12 relate to spinal cord degeneration?
Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important in fatty acid metabolism) – build up of methylmalonic acid which impairs spinal myelinization
How does Vitamin B12 deficiency relate to spinal cord degeneration?
Vit B deficiency results in increased levels of methylmalonic acid, which impairs spinal cord myelinization,
What does damage to the spinal cord due to Vitamin B12 deficiency result in?
poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateral corticospinal tract)
How is Vitamin B12 deficiency similar to folate deficiency?
Increased serum homocysteine which is similar to folate deficiency and increases the risk for thrombosis and there is increased methylmalonic acid (unlike folate deficiency)
