Anemia Flashcards
define anemia
- male Hb < 13.5 g/dL
- female Hb < 12 g/dL
what are clinical consequences of anemia
- conjunctival pallor
- atrophic glossitis
- fatigue → lethary (depending on severity)
- bounding pulses, palpitations, chest pain
- high output congestive heart failure, MI (severe anemia)
what are the essential building blocks in heme production and RBC maturation (hematopoeisis)
Renal ___ provides cytokine signaling for RBC maturation and release from bone marrow
dietary iron, folate, B12
Renal EPO provides cytokine signaling for RBC maturation and release from bone marrow
- dietary iron is absorbed in the ____
- dietary iron is absorbed in the duodenum
- Fe 2+ may be stored in the ___ bound with apoferritin to produce the storage form ___
- Fe 2+ may be stored in the enterocyte bound with apoferritin to produce the storage form ferritin
- Fe 2+ released from basolateral enterocyte surface via ____
- Fe 2+ released from basolateral enterocyte surface via ferroportin 1
- Fe 2+ is oxidized to Fe 3+ by ___
- Fe 2+ is oxidized to Fe 3+ by ferroxidase
- Fe3+ is bound and transported in the blood via ____ to sites of erythropoiesis: ____, and to the ___ where it binds to apoferritin for storage
- Fe3+ is bound and transported in the blood via transferrin to sites of erythropoiesis: bone marrow, and to the liver where it binds to apoferritin for storage
- When ferritin is filled, hepatocytes produce ___ which feeds back on enteric iron absorption to ____ ferroportin 1 activity
- When ferritin is filled, hepatocytes produce hepcidin which feeds back on enteric iron absorption to downregulate ferroportin 1 activity
duodenal iron absorption: ___ mg/day
iron recycling in liver and spleen: ___ mg/day
duodenal iron absorption: 1 mg/day
iron recycling in liver and spleen: 30 mg/day
in iron deficiency, what lab findings do you see?
transferrin saturation ?
ferritin ?
TIBC ?
- *decreased** transferrin saturation
- *decereased** ferritin
- *increased** TIBC
___ route is preferred in iron therapy
oral route is preferred in iron therapy
__ iron is best absorbed
ferrous (Fe2+) iron is best absorbed
list the ferrous iron oral drugs and what is co-administered for optimal absorption?
- ferrous sulfate
- ferrous gluconate
- ferrous fumarate
- ascorbic acid for optimal absorption
when do you give parenteral iron therapy?
chronic renal failure patients (high iron requirement)
hemodialysis patients (in combo with EPO)
list the parenteral iron formulations
- iron dextran - highest risk for type 1 HSN
- sodium ferric gluconate complex
- iron sucrose
list adverse affects of iron therapy
- black stool
- GI
- nausea
- epigastric discomfort
- abdominal cramps
- constipation
- diarrhea
what is the presentation of acute iron toxicity?
- history of iron ingestion by children
- direct GI irritation
- acue vomiting
- diarrhea
- abdominal pain
- mucosal ulceration and bleeding
describe the pathogenesis for acute iron toxicity
- free iron disrupts critical cellular processes
- metabolic acidosis
- widespread organ toxicity → shock, coma, death
- abdominal radiographs showing radio-opaque pills in stomach
how do you treat acute iron toxicity?
- activated charcoal is NOT effective (does not bind to iron)
- supportive care
- iron chelators:
- Deferoxamine
- Deferasirox
contrast deferoxamine and deferasirox
-
deferoxamine
- given IV to bind system iron
- promotes iron excretion (urine/feces)
- moderate & severe iron toxicity
-
deferasirox
- oral
- only effective at reducing iron absorption if given within 1 hour of ingestion
- used for chronic iron toxicitiy → outpatient iron chelation in transfusion dependent individuals
what can cause chronic iron toxicity?
- hemochromatosis
- cardiomyopathy
- bronze diabetes
- cirrhosis
- patients requiring frequent blood transfusions (thalassemia major)
desribe B12 absorption
- consumed in animal products
- salivary R binders bind to free B12
- pancreatic enzymes break up the complex and binds of IF from parietal cells → duodenum
- IF-cobalamin complex absorbed in terminal ileum
- transported bound to glycoproteins as transcobalamin I, II, III
The main storage site of B12 is in the ____ and takes ____ to develop B12 deficiency
The main storage site of B12 is in the liver and takes 5 years to develop B12 deficiency
list causes of B12 deficiency
- insufficient ingestion (strict vegans)
- defects in cobalamin absorption
- autoimmune disease: prenicious anemia
- surgery: gastrectomy, ileal resection
- small bowel disease: crohn’s, celiac, fish tapeworm infection (diphyllobothrium latum)
- Drugs
what drugs cause B12 deficiency?
- metformin, neomycin: alter gut flora
- nitrous oxide anethesia: converts cob(I)alamin to inactive form cob(III)alamin
- proton pump inhibitors, histamine 2 receptor antagonists: increase gastric pH
describe the clinical presentaiton of vitamin B12 deficiency
- anemia
- neurological symptoms
- parethesias
- subacute combined degeneration of spinal cord d/t abnormal myelination synthesis
- prolonged deficiency = irreversible nerve damage
- skeletal changes
- suppressed osteoblast activity → osteoporosis
what are the lab studies in B12 deficiency?
- megaloblastic macrocytic anemia
- leukopenia and/or thrombocytopenia
- decreased B12
- +/- antibodies agaist IF
- increased homocysteine
- increased methylmalonate
- increased methylmalonyl-CoA
explain B12 deficiency therapy and its adverse effects
- must be parenteral and continued for the duration of malabsorption
-
hydroxycobalamin
- preferred highly-protein bound form → stays in circulation longer
- cyanocobalamin
- no adverse effects!
what is the most common nutrient deficiency in USA?
Folate deficiency
describe folate absorption
- polyglutamylated dietary folate cleaved to monoglutamate via brush border enzymes in the jejunum
- enteres plasma via active and passive mechanisms
- in peripheral tissue: polyglutamylated again so it cannot diffuse into the plasma
- healthy individuals take 4-5 months for folate depletion (small hepatic store)
list risk factors for folate deficiency
- advanced age
- pregnancy
- chronic hemolytic anemias eg. sickle cell anemia
- alcohol abuse
- drugs
what drugs causes folate deficiency?
- inhibitors of DHF:
- trimethoprim
- pyrimethamine
- methotrexate
- phenytoin
describe the presentation of folate deficiency
- anemia
- no neurological sympytoms
- fetal neural tube defects in 1st trimester of pregnany
describe folate deficient lab study
- megaloblastic macrocytic anemia
- decreased folate levels
- increased homocysteine
- normal methylmalonic acid
describe folate therapy
- folic acid given orally for 1-4 months or until complete hematological recovery occurs
- prophylactic supplements should be give for:
- pregnant
- alcohol dependent
- hemolytic anemia
- liver disease
- exfoliative skin disease
- renal dialysis
list/describe erythrocytic growth factors
- erythropoeitin & darbepoetin
- stimulates JAK/STAT receptors
- Given parenterally in:
- chronic renal failure
- bone marrow suppression
- AE: hypertension, thrombosis
list/describe myeloid growth factors
- Filgrastim (G-CSF)
- Sargramostin (GM-CSF)
- stimulates JAK/STAT receptors
- increases production/function of neutrophils
- Sargramostin stimulates all myeloid pregenitor cells
- given parenterally in:
- cancer chemotherapy induced neutropenia
- bone marrow suppresion
- AE: bone pain, filgrastim = better tolerated
Describe interleukin 11
- myeloid growth factor
- acts via cell surface cytokine receptor
- stimulates growth of primitive megakaryocuytic progenitors
- increase platelets and neutrophils
- reduces need for platelet transfusions in chemotherapy recipients with prior episodes of thrombocytopenia
describe hydroxyurea
- reduces vascular occlusion in SCD
- increases HbF (reduces sickling)
- decreases expansion of neutrophil adhesion molecules
- increases endothelial production of NO
