Lecture 17 Flashcards
Pernicious Anemia
B12 and/or folate deficiency
Folate (B9)
- Needed for DNA synthesis and cell division
- Absorbed in duodenum and jejunum
What are the causes of B12 deficiency?
Nutritional deficiency (rare), gastrectomy (removal of a part or all of stomach), Atrophic gastritis (thin and inflamed stomach lining), Intestinal blind loop, parasite, ileal resection (removal or portion of ileum), Crohn’s Disease
What are the causes of folate deficiency?
Nutritional deficiency, malabsorption syndromes (Celiac disease, tropical sprue, jejunal resection), drugs, alcohol, pregnancy, lactation
Intrinsic Factor (IF)
- Secreted by gastric parietal cells
- Vitamin B12 binds
- Absorbed in ileum and transported to bone marrow
Hemoglobin
- 4 subunits: each with heme group
- each heme group: iron atom capable of binding oxygen molecule
- Humans have four functional alleles (alpha1 and alpha 2)
HbA
2 alpha and 2 beta globin chains; made by RBCs
HbA2
2 alpha and 2 delta chains
HbF
2 alpha and 2 gamma chains
Transferrin
Glycoprotein that binds and transports iron from gut and transported to marrow (delivered to developing RBCs/Hb)
What happens to iron after RBCs reach their lifespan?
120 days: ingested by macrophages -> iron extracted from Hb and recycled to plasmin transferrin
Iron Deficiency Anemia
- Chronic blood loss (iron deficiency) or impaired absorption (celiac sprue, malabsorption of fats, chronic diarrhea)
- Iron stores completely depleted (hypochromic microcytic anemia: small (microcytic) and pale (hypochromic) RBCs)
Normochromic Normocytic Anemia
- RBCs normal color and size but decreased number
- Results from nutritional deficiency and abnormalities in erythropoietic growth factor production (Cytokines)
- Chronic inflammation increases synthesis and release of hepcidin
Hepcidin
hormone produced in liver that regulates iron metabolism by binding to ferroportin and inhibiting it (causes retention of iron within enterocytes, hepatocytes, macrophages due to decrease in blood iron levels)
Ferroportin
Protein that facilitates export of iron from cells to bloodstream
Hemochromatosis
hereditary disease of intracellular accumulation of iron in organs (liver iron deposits: cirrhosis and liver cancer)
HFE
-Hepatocyte membrane protein
- Regulation of hepcidin production
What happens if there is a defect in HFE?
Poor regulation of hepcidin -> mucosal transfer or iron -> plasma transferrin -> iron overload
Divalent Metal Transporter (DMT1)
Transports ferrous iron (Fe2+
Hemojuvelin (HJV)
membrane bound and soluble protein receptor (HFE2) -> juvenile hemochromatosis
Thalassemia
- interruption of alpha and beta globin chain formation by RBCs
- Alpha and beta forms
- Genetic (autosomal recessive)
- Major: homozygous
- Minor: heterozygous
- Trait: alpha form when combination of 2 genes deleted
- Form depends on alpha globin subunit, number of genes, and type of inheritance
Hemolytic Anemia
Caused by premature destruction of RBCs (and decrease in Hb)
Hemolysis
Breakdown of RBS (release of Hb into bloodstream)
What happens if Hb has missing beta chains?
- Extra alpha chains collect in RBCs
- Damage cell membrane
- Hemolysis and anemia
- Blood transfusions are only treatment
- Iron chelation therapy: removes excess iron
