Exam 2: Lecture 37 b

Question 1

What are the causes of macrocytic anemia?

Answer 1

• Megaloblastic anemia–> B12 and folate deficiency
• chronic liver disease/alcoholism
• hypothyroidism
• Drugs–> phenytoin, Zidovudine, methotrexate and other anti-folates or chemotherapeutic agents that impairs DNA synthesis
• bone marrow disorders–> myelodysplastic syndrome, leukemias, multiple myeloma
• red cell agglutination ( Rouleaux in multiple myeloma or cold agglutinin

Question 2

Describes B12 metabolism

Answer 2

• Diet: consumed via meat products
• Stomach: pepsin and acid causes protein to separate from B12; R factor binds to B12; Intrinsic factor secreted by parietal cells
• duodenum: Pancreatic proteases release B12 from R factors; IF binds to B12
• ileum: IF-B12 complex attaches to IF-B12-R (cubulin) on intestinal cell and is absorbed
• Blood: transcobalamin II carried B12 to the body’s cells where it is used and to the liver for storage
• Liver: B12 stored and some released into the small intestines via bile; large body stores of B-12 (2-5mg)—> last for years

Question 3

Describe the metabolism of Folate

Answer 3

• diet–> water soluble, fortified in cereals and grains—> polyglutamate form
• jejunum: cleaved to monoglutamate form; absorbed into intestinal cells
• blood to cells–> enters via folate receptor; stored in liver and bile
• body stores are small and can be depleted in months (5-10 mg)

Question 4

Folate–> DHF–> THF—> METHYL THF ( methionine synthase with B12 cofactor)–> produces methionine from homocysteine

Answer 4

• PRODUCES THYMIDINES
• produces methionine
• both needed for synthesis of DNA
• deficiencies in either B12 or folate lead to increases homocysteine

Question 5

What is cobalamin needed for?

Answer 5

• involved in FA metabolism and neuronal myelination
• B12 deficiency will lead to neurotoxicity
• B12 deficiency will lead to increase in methylmalonic acid levels, not FOLATE DEFICIENCY
• methylmalonyl CoA to Succinyl CoA (B12 cofactor and methylmalonyl CoA mutase)’
• DNA synthesis

Question 6

What tare the causes of B12 deficiency?

Answer 6

• strict vegan
• Pernicious anemia–> deficiency of IF due to autoantibodies against parietal cells or IF; associated with autoimmune atrophic gatsritis and other autoimmune diseases like thyroididtis and vitiligo, DM
• Achlorydria (absence of hydrochloric acid in gastric secretions)–> atrophic gastritis or proton pump inhibitors, H2 blockers
• Post surgical –> gastrectomy, gastric bypass/ bariatric surgery, ileal resection
• intestinal disorder–> pancreatic insufficiency (chronic pancreatitis); malabsorption ( Crohn’s, bacterial overgrowth, celiac disease, and tapeworm infection)

Question 7

What is the cause of folate deficiency?

Answer 7

• dietary is rare since its fortified in cereals and grains
• alcoholics–> alcohol inhibits folate absorption and poor dietary intake
• post surgical
• drugs: methotrexate, trimethoprim, pyrimethamine, phenytoin
• high demand for folate—> hemolytic anemia and pregnancy–> provided to prevent neural tube defect

Question 8

Describe the histology of megaloblastic anemia

Answer 8

• macro- ovalocytes (more oval than other macrocytes seen in liver disease)
• hypersegmentaed neutrophils (any with > 6 lobes; 5% with >5 lobes)
• may also see thrompocytopenia and neutropenia wwhen more severe

Question 9

What are the symptoms of megaloblastic anemia?

Answer 9

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Question 10

Diagnosis

Answer 10

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Question 11

Treatment B12 deficiency

Question 12

Treatment folate deficiency

Question 13

Transfusion medicine