8. Nutritional Deficiency Anemias Flashcards
which 3 nutrients are relevant to anemias, and general type?
Iron defic: microcytic anemia (affects hemoglobin synth)
Folate and B12 defic: macrocytic and megaloblastic anemia (affects DNA synth)
total iron pool for men vs women
3540 mg vs 2450 mg
iron cycle
- Fe recycled b/w functional and storage pools
- Some shedding each day, but balance maintained by regulating absorption of dietary Fe in proximal duodenum
○ Balance thanks to loss in keratinocytes, enterocytes, and endometrium shedding - Absorbed iron (gut) bound to transferrin for transport to marrow
○ Delivered to developing RBCs & incorporated into Hb
○ Erythroid precursors in marrow w/ high affinity receptors for transferrin
§ Fe import through receptor-mediated endocytosis - Mature RBCs rel. into circulation
- Life of 120 days
- Post ^ ingested by macrophages in spleen, liver, and bone marrow
- Fe extracted from Hb and recycled to plasma transferrin (synth in liver)
- Some shedding each day, but balance maintained by regulating absorption of dietary Fe in proximal duodenum
regulation of Fe absorption
- Hepcidin = circlulating small peptide
○ Synth and released from liver re: increase in intrahepatic Fe levels- Q storage sites replete w/Fe and erythropoietic activity is normal, hepcidin is high
○ Downregulation of ferroportin and trapping of most of the absorbed iron
○ Lost duodenal epith cells are shed into gut - Q storage sites have no Fe or w/ stimulated erythropoietic activity, hepcidin levels fall
○ Ferroportin activity increases
○ Greater fraction of absorbed iron transferred to plasma transferrin - Non-heme iron (Fe3+ ferric form) is reduced to Fe++ ferrous state by brush border ferrireductase pre abosrption
○ Transported in thanks to DMT1
○ Variable, affected by diet - The mucosal “barrier” is insufficient to prevent the inappropriate absorption of supraphysiologic amounts of iron, e.g. accidental ingestion of medicinal iron.
- Q storage sites replete w/Fe and erythropoietic activity is normal, hepcidin is high
heme vs nonheme iron
20-25% absorbable vs 1-5% absorbable
Fe absorption vs requirements
- Daily requirement: absorbed from 10-20 mg dietary Fe
○ Men and postmenopausal women: 8 mg/d RDA
○ Premenopausal women: 18 mg/d RDA
○ Pregnant women: 27 mg/d RDA- Absorption varies inversely w/stores
○ Iron sufficiency: absorb ~5% from diet
○ Iron deficiency: absorb >10% from diet
- Absorption varies inversely w/stores
groups at increased risk for iron deficiency
Groups at ^ Risk for Fe deficiency
- Women of childbearing age, esp w/lots of menstrual loss - Pregnant women - Teenage girls - Preterm and LBW infants - GI disease and malabsorption - Renal failure, esp on dialysis (platelet dysfunction and occult GI bleeding) - Regular blood donors
markers of Fe deficiency
- Decreased serum iron
- Increased serum transferrin (TIBC)
- Decreased transferrin saturation
○ % sat = Fe/TIBC X100% - Increased soluble transferrin receptor
- Decreased ferritin (reflects low storage iron)
○ Acute phase reactant**
w/prolonged inflammation, may have it increased
lab findings of iron deficiency anemia (peripheral blood smear)
decreased MCV, decreased MCHC
clinical manifestations of Fe deficiency anemia
○ Sx of anemia
§ Fatigue, headache, irritibility
○ Pica
○ Epithelial changes (uncommon) (angular stromatitis, koilonychia, mucosal web)
○ Children
§ Retarded growth, impaired cognitive development
○ Pregnancy
Increased risk of preterm birth and LBW
Tx iron deficiency anemia
○ Oral iron salts = effective and cheap
§ Dose: 150-200 mg/day elemental iron in in 3 divided doses
□ FeSO4 300 mg provides 60 mg of elemental iron. 60 x 3 = 180 mg/day. The absorbed amount at this dose (assuming 10% absorption) is only 18 mg.
§ Adverse effects: GI irritation
□ Nausea
□ Constipation
□ Diarrhea
○ Parenteral iron
§ Selected pts
□ Dialysis dependent renal failure treated w/ EPO
Hematopoietic response no faster than w/ oral iron and oral iron is safer (less risk of anaphylaxis)
treatment response to tx for Fe deficient anemia
○ Hematopoietic response § ^ retic. □ Starts 3-4 days □ Peaks 5-10 days § ^ Hb □ Starts 2 weeks □ Takes 2-3 months ○ Rx after anemia is corrected to replenish iron stores § Monitor serum ferritin
Treat underlying cause
pathophys of anemia of chronic disease
cytokine mediated induction of hepcidin and inhibition of erythropoiesis (not responsive to supplemental iron)
iron deficiency vs anemia of chronic disease: iron, ferritin, cytokine levels
iron: reduced in both
ferritin: normal to increased in chronic, reduced in iron deficiency
cytokine: increased in chronic, normal in iron defic
macrocytic vs megaloblastic anemia
Not ALL macrocytic anemias are megaloblastic (but all megaloblastic anemias are macrocytic)
- Macrocytic: big cells - Reticulocytosis, liver disease, other conditions can also cause big cells that are not megaloblastic
Megaloblastic cell shave a characteristic nuclear maturation defect
daily req folate
Daily req: 50-200 micrograms (RDA 400 micrograms)
- Increased req in pregnancy, lactation, chronic hemolysis, and psoriasis - Avg. diet supplies 500 g/day - Veggies, cereal, flour - Destroyed by cooking
daily req B12
Daily req:2-5 micrograms (RDA 5 micrograms)
- Avg US diet = 5-30 micrograms q day - Ultimate source is bacteria - Human source is meat, fish ,eggs, milk
excess of what molecule with folate defic? B12 defic?
excess homocysteine for either, excess methyl malonyl only for B12 defic
absorption, dist, and body stores folate
- Absorbed in jejunum and proximal ileum
Body stores 1-3 months
absorption, dist, and body stores B12
- saliva has R binders that bind B12 as it travels down to stomach
- stomach: B12 released from food thanks to action of pepsin, binds to R-binders
- Duodenum: released from R-binders thanks to pancreatic proteases, binds intrinsic factor (secreted by gastric fundic parietal cells)
- terminal ileum: absorbed per cubulin (IF-B12 complex)
- bloodstream: carried by transcobalamins I-III
- Transcobalamin II required for transfer to tissues (CRITICAL)
- excess excreted in urine
conseq of B12 defic
- Peripheral neuropathy (paresthesias, hyporeflexia)- spinal cord degeneration (weakness, hyperreflexia, reduced vibration and position sense)
• Sensory and motor tracts involved in patchy distribution
○ Many manifestations
• Demyleination followed by long tract loss - Memory loss, disorientation, depression
- Anemia (pallow, lassitude, dyspnea, palpitations)- GI (wt loss, diarrhea, abdominal pain, glossitis)
- Reproductive (infertility, fetal loss)
- Psych (depression, confusion)
- Immune (autoimmune diseases)
- Behavioral (restricted diet, uncooked fish)
- White centered retinal hemorrhages
conseq of Folate defic
- Neural tube defects
• 1st gestational month
- Intestinal dysplasia • malabsorption - Hypercoagulable state - Anemia • Macrocytic but smaller if accompanied by Fe defic or thalessemia (MCV could be normal!)
Pancytopenia
causes of folate defic
- Dietary deficiency: babies fed on porridge, teens living on coke and chips, medical students living on coffee and alcohol, fad dieters
- Intestinal diseases
• Chrons
• Whipple
• Gluten sensitivity
• Proximal ileal resection - EtOH and folate defic
• >80 mg/day directly toxic effect w/ megaloblastosis and vacuolated normoblasts
• Prevent w/one nutritious meal q day
• Subacute (low dose alcohol for mult days)
○ Malabsorption
○ Reduced tx release
○ Interrup of hepatoenteric circulation
○ Increased urinary excretion
causes of B12 defic
- Dietary insuffic • Vegans, rare - IF deficiency • Congenital defic of IF • Gastric resection • Destruction by autoantibodies Pernicious anemia - Competitive utilization • Bacterial overgrowth ○ Blind loops ○ Diabetics • Fish tapeworm ○ Diphyllobothrium latum ○ Absorbs >80% of host's B12 - Ileal disease • Tropical sprue, resection, Chrohn disease
hematologic conseq of B12/folate defic
large oval RBCs and PMNs
Megaloblastic changes in bone marrow:
- Large polychromatophillic normoblasts w/poorly condensed chromatin
- Nuclear-cytoplasmic dissynchrony
Giant bands
failure of apoptosis
vitiligo
Signs and symptoms
○ Vitiligo
- Acquired disease, though familial
- Autoimmune cause for IF deficiency
- Type A gastritis (parietal cells destroyed)
- Antiparietal canalicular antibodies (90%)
- Type I anti-IF antibodies block IF binding
- Type II anti-IF antibodies block absorption
• Serum and gastric juice
- Assoc w/other autoimmune diseases
• Hashimoto’s thyroiditis
schilling test
- B12 absorption test
- Oral radioactive B12 given after IV load normal B12
○ % radioactive B12 est from 24 hour urine collection
○ If abn, repeated w/ supplementation of IF
○ If still abn, antibiotics to tx bacterial growth
○ If still abd, pancreatic enzyme supplementation
- Oral radioactive B12 given after IV load normal B12
Population health: folate supplementation for prevention of neural tube defects
- All women who could become pregnant should consume 500 micrograms/day of folate
other causes of megaloblastic anemia
- Enzyme deficiency
○ Dihydrofolate reductase, homocysteine methyltransferase- Receptor deficiencies
○ IF defic, ileal receptor-Imerslund-Graesbeck disease - DNA synthesis inhibitors
○ Chemo drugs, AZT, antimicrobials - TB ileitis leading to malabsorption, causing B12 defic and brain atrophy
- Primary bone marrow disease (leukemia myeloproliferative disorder)
○ Disordered blood cell production incl some large RBCs from skipped divisions
○
○ Unrelated to vitamin defic
- Receptor deficiencies
