Iron, Folate, B12 Metabolism Flashcards
What are recommended daily amounts of iron?
Males 10mg per day recommended. Females 18mg per day recommended. We absorb about 1mg per day (10%)
What are the fxns of iron?
Oxygen carriers-hemoglobin. Oxygen storage-Myoglobin. Energy production-Cytochromes. Krebs cycle enzymes. Liver detoxification
What happens with hemochromoatosis (iron overload)?
Can take years to build up. Hemosiderin (extra iron in ferritin) deposits in: Liver (cirrhosis). Pancreas (diabetes). Joints (arthritis). Skin (dermatitis)
What are symptoms of hemochromoatosis?
Fatigue. Lethargy. Lack of menstrual period
What are the blood tests for iron?
Serum Iron. TIBC= Total Iron Binding Capacity. Transferrin saturation
How is iron transported in the blood?
Red cells- As hemoglobin. Cannot be exchanged. Plasma- Bound to Transferrin. Carries iron between body locations. Iron taken up into cells by transferrin receptors
What is transferrin and its relationship to iron?
Each molecule binds can bind two Fe molecules. Contains 95% of serum Fe. Production is decreased in iron overload.Production increased in iron deficiency. Measured in blood as a marker of iron status.
What is the fxn of transferrin receptors and how does it work?
Collects iron from transferrin for uptake into cells. Receptor + transferrin endocytosed. Iron released into cell via Iron transporter (DMT1). Receptor + transferrin return to cell surface. Transferrin released
What is the significance of soluble transferrin receptors?
Truncated form of cell surface receptors found in the circulation. High levels with iron deficiency. Low levels with iron overload
How is serum iron used as a clinical test?
Measures all serum iron (not in red cells). Of limited use on its own. Useful for interpretation of iron status only if grossly abnormal – eg iron poisoning. Commonly combined with serum transferrin to express transferrin saturation
Where is iron stored?
the liver and nearly all other cells. Small fraction found in circulation (contains less than 1% of serum iron). Ferritin stores iron and releases it in a controlled fashion.
What are physiological causes of iron loss?
Cell loss: gut, desquamation. Menstruation (1mg/day). Pregnancy, lactation
How is iron re-used?
Old cells broken down by macrophages in spleen and other organs. Iron transported to liver and other storage sites. Red cell iron recovered from old red cells. Very little iron lost in routine metabolism
Describe iron scavenging.
Breakdown of red cells in the circulation: Free hemoglobin binds haptoglobins -> taken up by liver
Free heme binds hemopexin -> taken up by liver
Heme passing through kidney reabsorbed
How is iron homeostasis regulated?
by adjusting iron intake
Describe iron absorption
Occurs in the duodenum. Taken up as ionic iron or heme iron. Only 10% of dietary iron absorbed. Dietary iron usually in excess
When is iron absorption increased?
Low dietary iron. Low body iron stores . Increased red cell production. Low haemoglobin. Low blood oxygen content. lead to decreased hepcidin production
When is iron absorption decreased?
Systemic inflammation. Leads to increased hepcidin production
What is hepcidin (Hepatic bacteriocidal protein)?
Master iron regulatory hormone. Inactivates ferroportin. Stops iron getting out of gut cells. Iron lost in stool when gut cells shed. Leads to decreased gut iron absorption
How is iron released from cells?
Ferroportin present on cell surface to release iron. Found on gut cells, liver cells and macrophages. Requires cofactor to oxidize iron to allow for binding to transferrin-Hephestin in gut and Ceruloplasmin in other cells
What blocks iron release from all cells?
hepcidin
What laboratory changes are seen with iron deficiency?
Low iron (poor specificity). Low ferritin (excellent specificity). Elevated Transferrin (TIBC). Low transferrin saturation. Hypochromia, microcytosis. Anemia
What are the stages of iron deficiency?
Reduced iron stores. Iron deficient erythropoiesis. Iron deficient anemia
Why is methionine important?
Methionine is an essential amino acid. Comes from meat, fish and dairy products. Used in Europe to treat depression, liver disease, inflammation and certain muscle pains.
Why are folates important?
Folates support red blood cell production. Helps prevent homocysteine build up in blood. High levels leads to inflammation/coronary heart disease
What are fxns of vitamin B12?
Plays a role in recycling of folates and in methionine synthesis. required for manufacturing of DNA
What are daily requirements of vitamin b12?
about 5ug. Normal liver/tissue storage is about 1000 times the daily need
What is megaloblastic anemia?
Blood disorder characterized by anemia, with red blood cells that are larger than normal. usually results from a deficiency of folic acid or of vitamin B-12. Hypersegmented neutrophils on CBC
What are disorders associated with vitamin B12 deficiency?
neurological-secondary deficiency of methionine deprivation in the nerves. Parathesias. Homocysteinuria- Kyphosis (hunchback), Lens adaptation, Atherosclerosis.
How is vitamin B12 absorbed?
The gastric phase- IF (Intrinsic factor) binds to B12. The intestinal phase- IF-B12 complex is absorbed in the ileum through specific llieal receptors.
What are dietary mechanisms of B12 deficiency?
Comes from meat. A vegan diet (no B12 in all plants)
What is most common cause of vitamin B12 deficiency?
Pernicious anemia (a form of megaloblastic anemia; also known as Biermer’s anemia or Addison’s anemia)
What is pernicious anemia?
underlying abnormality is an atrophic gastric mucosa. Failure to secrete normal gastric secretions INCLUDING intrinsic factor, which is ESSENTIAL for absorption of B-12
What are impaired absorption mechanisms of B12 deficiency?
Lack of IF in the stomach. Gastric surgery. Surgical removal of the ileum. Crohns disease, IBS, Ulcerative Colitis. Bacterial overgrowth in ileum. Pancreatic insufficiency (chronic pancreatitis). Metformin (Common diabetic oral medication). Autoimmune disorders eg Graves or Lupus. ETOH abuse
What is folate and its fxn?
Vitamin B9. Folate (the anion form of folic acid). Need a good balance between folate & B12. Participates in a single carbon transfer (e.g., synthesis of choline, serine, glycine, methionine, nucleic acids)
What happens as a result of folate deficiency?
Hyperhomocysteiemia, a risk factor for cardiovascular diseases. Megaloblastic anemia (which results from a deficiency of vitamin B12 and folic acid)
How does omeprazole cause folate deficiency?
Reduces iron absorption if taken at same time. Reduces acidity which in turn reduces iron absorption. Also reduces magnesium absorption
When do you see basophilic stippling?
Pernicious anemia, seen in alcoholics and lead poisoning
When do you see spherocytes?
hemolytic anemia
When do you see target cells?
chronic liver disease
When do you see helmet cells (schistocyte)?
Fragment of cell. Indicative of hemolytic anemia or acute leukemia.
When do you see Burr cells?
Hemolytic anemias, iron deficiency or acute blood loss
How do OTC H2 blockers (Tagamet, Ranitidine cause folate deficiency?
Reduces absorption of iron, folate &B12
