Week 3 Macrocytic Anemia Flashcards
What anemias are caused by defects in DNA metabolism
- when DNA synthesis is impaired it affects all rapidly dividing cells of the body like skin, GI and hematopoietic tissues .
-The effects of hemotologic cells causes Megaloblastic Anemia
What causes MA
- impaired DNA synthesis from B12 or folate deficiency
-known as nutritional anemia or even hemolytic anemia
-B12 and folate needed for thymidine which helps with DNA synthesis and repair (no division, apoptosis)
-results in ineffective erythropoiesis and megaloblastic morph of RBC precursors
-fewer RBCs released into circulation
-the cells that are released are larger with fewer cell divisions and immature nuclei
-pancytopenia - all three blood lines are affected
-cytoplasm develops normally as RNA function is not impaired
-RNA function is not affected by the deficiency because RNA contains Uracil instead of thymidine
-NUCLEAR CYTOPLASMIC ASYNCHRONY - nuclear maturation lags behind cytoplasmic
what symptom related to the alimentary tract will a person with MA have
Glossitis
-smooth tongue
-very sore
also a loss of epithelium in the GI can cause gastritis, nausea or constipation
how does a b12 deficiency present and can be caused by, sources of B12
Neurological problems
-memory loss
-personality changes
-numbing in fingers and toes
-vertigo
-loss of vibratory senses
caused by
-cant extract b12 from food or haptocorrin
-dont have the intrinsic factor
-increased need pregnancy, lactation
-inhertied issues with absorption
-hpylori,
-blind loop syndrome
B12 sources
-cant get it from food
-need meat fish dairy eggs
-not heat liable
how does a folate deficiency present and what is it caused by, sources of folate -B
causes
-inadequate intake
-increased need pregnancy , prevent neural tube defects
-impaired absorption
-impaired use
-loss through renal disease
presented as
-risk of CVA
-depression
-peripheral neuropathy
-deficiency during pregnancy can cause Spina Bfida
sources
-leafy greens
-legumes
-heat liable
what do you see in a PBF for MA
MCV>100fL
- oval macrocytes
-hypersegmented neuts
-pancytopenia
how is B12 transported through the body
-food with B12 is bound to enzymes which are denatured by gastric acid and cleaved by pepsin
-once b12 is released it gets bound to first carrier protein haptocorrin in stomach
-in the SI trypsin degrades haptocorrin releasing b12
-Gastric parietal cells secrete intrinsic factor (2nd carrier protein) which binds b12 in duodenum
-b12 + intrinsic factor complex goes to the terminal ileum where the ileal enterocytes take it up by endocytosis
-inside the enterocyte, B12 is freed form IF and binds to transcobalamin/TC (3rd carrier protein) which takes through portal circulation
-in this way B12 reaches the liver and BM
-in BM, RBC pronomoblast membrane receptors for TC and B12 take it in for DNA synthesis
What is pepsin , trypsin and Haptocorrin
Pepsin - enzyme released by chief cells in the stomach which degrade food proteins into peptides
Trypsin - Digestive enzymes produced by the pancreas that breaks down proteins in the small intestine
Haptocorrin - also Transcobalamin I- salivary carrier protein that protects B12 from acids as it moves around in the stomach
What are partiel cells, intrinsic factor and enterocytes
Parietal cells: Mucosal epithelial cell in stomach that releases gastric acid HCI and intrinsic factor
Intrinsic factor - glycoprotein released by parietal cells needed for intestinal absorption of b12 by enterocytes
Enterocytes - epithelial cells in intestine mucosa, absorbs nutrients and transports them into circulation
three ways that impaired absorption occurs in B12 deficiency
1- failure to separate B12 from food protein
Food cobalamin malabsorption - when the body cant release B12 from food or intestinal proteins to bind to intrinsic factor . Caused by low gastric acidity, linin atrophy, after gastric bypass
2-failure to separate b12 from haptocorrin
Decrease in gastric acid production or low trypsin makes it so that B12 stay attached to haptocorrin in intestine so it isnt available for intrinsic factor. Instead of B12 being absorbed its pooped out
3-Lack of intrinsic factor
-Most significant cause due to pernicious anemia . Can also happen because of H pylori, gasterctomy, or herediatry IF deficiency
What is pernicious anemia and how is it detected
-b12 deficiency from autoimmune disease that destroys gastric parietal cells
-leading to lack of gastric acid and intrinsic factor
-over time atrophic gastritis develops causing pt to develop AB to intrinsic factor and gastric parietal cells
detection
-Anti intrinsic factor AB found in serum of pt with PA detected via immunoassay -very specific
-Parietal cell AB in serum of pt with PA- detected by indirect fluorescent AB techniques or ELISA- non specific
what are 2 inherited erros of B12 transport and absorption
Imerslund- Grasbeck Syndrome
-autosomal recessive
-reduced endocytosis of IF + b12 complex by ileal entrocytes
Transcobalamin deficiency
-autosomal recessive
-b12 not physiologically available
how does competition for B12 cause B12 Deficiency
-when the body and internal organisms compete for B12
-can result in MA
Fish Tapeworm -Latum
-splits B12 from IF so it cant be used by the host
Blind loops
-stenotic intestines from surgery or inflammation
-stenotic areas become overgrown with intestinal bacteria which competes with host for B12
how does impaired absorption lead to folate deficiency
- folates from food must be hydrolyzed in the gut before absorption in the small intestine
-only 50% of what you eat is available for absorption
-impaired absorption can result from
-transporter protein deficiency
-celiac (also b12)
-sprue (also B12)
-bowel disease (also b12)
how can drugs affect folate absorption
antiseizure
antibaterial
antineoplastic
MTX- folate inhibitor
drugs can decrease or impair folate metabolism
Folic acid supplementation should be able to override for example for pt who lose folate through kidney because of dialysis. helps to prevent MA
