• required nutrients
  • iron
  • folic acid
  • vitamin B12
• GF's
  • IL-1, 6, 3
  • G-CSF
  • GM-CSF
  • epoetin

• absorbed from duodenum and proximal jejunum (10-15% dietary iron absorbed)
• increased absorption
  • acidity
  • response to low iron stores
  • pregnancy
  • vitamine C

Only ferrous form absorbed

• meat (well absorbed heme iron)
  • facilitates absorption by stimulating gastric acidity
• vegetables (much less available)
  • bound to phytates
  • phosphates inhibit absorption

non heme iron in foods must be reduced to ferrous iron (usually ascorbate)

• active transport process for iron across the mucosal surface
• storage form of iron is ferritin
• transferrin transports iron from mucosal cell to the plasma

• structure- beta globulin that binds iron as the ferric form
• function- transports to marrow and tissues
• mechanism of action
  1. bind to transferrin receptor on cells
  2. complex is internalized and ferric iron is released into endosomes
  3. transferrin and R are recycled

• location
  • intestinal mucosal cells
  • macrophages in liver, spleen, bone
• clinical use- estimate total body stores of iron
  • detectable in plasma and in equilibrium with storage ferritin in the reticuloendothelial tissue

down regulates iron absorption in a state of iron overload

• regulated by free iron
  • if low, synthesis in hibited and iron binding shift to transferrin (upregulate transferrin R synthesis)
  • if high, synthesis is stimulated and iron sequestered as ferritin and organs protected from iron's toxic effects

• no excretion mechanism
  • mainly lost by exfoliation of intestinal cells
  • could lose by bleeding
  • lost in trace amounts of bile, urine, sweat
• if body iron stores high, iron stored as ferritin
• if iron stores low, iron transported to bone marrow for Hb production

• epi- seen in young children (10 tablets can be lethal)
  • prevention- childproof containers out of reach
• clinical syndrome- necrotizing gastroenteritis
  1. vomit, abdominal pain, bloody diarrhea
  2. shock, lethargy, dyspnea follow
  3. severe metabolic acidosis
  4. coma and death
• tx
  • whole bowel irrigation to remove unabsorbed pills
  • deferoximine to chelate iron that has been absorbed and promote excretion
  • supportive care for bleeding, acidosis, shock

• also known as iron overloard, hemochromatosis
• cause- excess iron is deposited in organs (dont produce hepacidin) 
  • heart
  • liver
  • panceras, etc.
• can lead to organ failure, death
• tx- phlebotomy

• iron deficiency anemia
  • usually seen in states of increase iron needs
    • infants
    • children
    • pregnant women
    • lactating women
  • gastrectomy pts and pts with severe bowel disease (malabsorption syndreom)
  • adults with blood loss
• tx with oral iron preparations
  • ferrous salts which are 25% absorbed

• epigastric distress
• cramps
• constipation
• diarrhea
• black stools

lessen by taking with meals or after meals, changing preparation, dosage adjust

• indication- pt who cant tolerate oral iron or cannot absorb it
• PK
  • stable comples of ferric hydroxide
  • low MW dextran (50 mg Fe per mL)
  • administer via IM injection or IV

• pain on injection
• tissue discoloration
• headache, light headedness
• fever
• arthralgia
• nausea
• vomiting
• back bpain
• flusing
• urticaria, bronchospasm
• rare anaphylaxis, death

• neurological syndrome
  • begin parasthesia and weakness
  • cause ataxia, spacicity
  • due to degeneration of myelin sheath followed by disruption of axons in spinal cord
• chemical structure
  • porphyrin ring structure
  • central cobalt atom attach to a nucleotide
  • active form- desoxyadenysl-Co and methyl-Co

very strict vegetarians after many yrs without meat, eggs, diary products

But usual cause is malabsorption

• complex with IF
• absorbed at distal ileum
  • highly specific receptor mediated mechanism
  • malabsorption (usually due to loss of IF or malfunction of distal ileum absorption mech)
• transport bound to transcobalamin II w/ excess stored in liver

• without it, we see decrease in tetrahydrofolate aka folate deficiency
  • we get decrease DNA synthesis
• leads to decrease in Met (no methyl donation), and can give rise to peripheral neuropathy

So we could correct B12 def. anemia with folic acid but it would not help the neurologic change

• parenteral injection as hydroxycobalamin (remain in circulation longer)
• to replenish stores given daily
• maintenance doses every month for the rest of life
• hematologic response is rapid (marrow return to normal within 48 hrs)

• newborn neural tube defects
• megaloblastic anemia

• storage- liver and other tissue
• excretion- urine and stool
• sources- green vegetables, yeast, liver, fruits
  • cooking can destroy 90% of folate'
• recommended intake- 400 micrograms per day
  • if pregnant, lactating, 500-600
  • 400 micrograms prevent NTD

1. reduced methylated monoglutamates are absorbed
   1. hydrolyzed to monoglutamate
   2. reduced and methylated to form N5- methyltetrahydrofolate
2. transported to tissue and act as methyl donor for formation of methylcobalamine
3. stored in cells as polyglutamate

• folate (pteroylglutamic acid)
• folinic acid (5 formyltetrahydrofolate)
  • Leucovorin
• folate reductase reduce folate to dihydrofolate and then to tetrahydrofolate
  • bypass need for B12

• extreme diets lacking veggies, eggs, meat
• old people
• alcoholics (pts with liver disease)
• pregnant women
• hemolytic anemia
• malabsorption syndromes
• renal dialysis pts
• drugs (oral contraceptions, INH, phenytoin)

• must remove multiple Glu groups for absorption
• readily absorbed in jejunum

• not cleared by dialysis
• liver major site of degredation
• half life of 4-13 hrs in pts with chronic renal failure
• chemistry
  • heavily glycosylated
  • produced in mammalian expression system using recominbinant DNA tech

• made in kidney peritubular cells
• made in response to tissue hypoxia
• target cells are the CFU-E (precursors)
• stimulates RBC prolif. and differentiation
• induce release of reticulocytes from marrow

• anemia due to chronic renal failure
  • failure usually ue to concurrent iron deficiency
• anemia due to other disorders
  • esp. with low serum EPO
  • anemia due to AZT in HIV pts

• HTN
• thrombitic complications
• seizures for those on dialysis

Due to rapid increase in Hb and Hct, so minimize by raising Hct slowly, monitoring and tx HTN.

• chemistry- four AA's in epoetin have been mutated such that additional carbs can be added, prolonging half life (about 24 hour half life)
• mechanism- act on progenitor cells to stimulate RBC production like epoetin

• can give drug once a week or once every three weeks due to longer half life
• clearance slowed and half life 2-3 times longer than epo

• may increase bp in renal failure
  • hypertensive encephalopathy, seizures may occur
  • may require antihypertensives
  • increase in CV events due to increase Hb
• rarely, rash and urticaria

generally well tolerated

• function
  • stimulate progenitor cells already committed to neutrophil lineage
  • activate phagocytic activity of mature neutrophils
  • mobilize hematopoietic stem cells of all lineage (great for SCT)
• chemistry- non glycosylated and produced in bacteria

• function
  • broader biological function
  • stimulate proliferation and differentiation of granulocyte progenitor cells and RBC and megakaryocyte progenitors
  • less able to mobilized stem cells
• chemistry- partially glycosylated found in three molecular species in yeast

• half life is 2-7 hrs after IV or subQ admin

• chemotherapy induced neutropenia (reduce duration and nadir)
• autologous SCT- reduces time for engraftment and time to recovery from neutropenia
• ability to mobilize stem cells has made the use of peripheral blood stem cells to autologous SCT possible (avoid risk and discomfort of bone marrow transplantation)

• bone pain
• local skin reaction at injgection site
• cutaneous necrotizing vasculitis
• splenomegaly

Better tolerated than GM-CSF

• reduce neutropenia after cytotoxic chemo (reduce duration of neutropenia and nadir)
• autologous transplatation (reduce time for engraftment and time to recovery from neutropenia)

• fevers, flu like syndromes
• bone pain
• diarrhea
• malaise
• arthralgias/myalgias
• first dose- flushing, hypotension, NV, dyspnea with fall of arterial oxygen
• capilary leak syndrome with peripheral edema and pleural/pericardial effusion

• function- stimulate production of megakaryocytes and thrombocytes
  • heal GI lesions
  • induce protein syn.
  • inhibit adipogen.
  • inhibit proinflam cytokines
  • increase osteoclasts
  • stimulate neurogenesis
• recombinant form- Oprelvekin
  • indication- prevent thrombocytopenia
  • cause sodium retention (prevent with furosimide)