Anemia Flashcards
what is anemia?
Anemia - reduction in the Hemoglobin or hematocrit (% of whole blood that is comprised of red blood cells) or red cell number
what is MCV and how is it used for diagnosis?
MCV = mean corpuscular volume Unit - femtoliters (fl.) - (10-15 liters) Normocytic (MCV = 80-96 fl) – cells are normal in volume. Macrocytic anemias (MCV = 150 fl) – larger than normal cells Microcytic anemias (MCV = 50 fl) – cells are smaller than normal
What is erythropoiesis?
formation of RBCs
Pluripotent stem cells break into three different paths
- growth factors and erythropoeitin = erythrocytes (RBCs)
- Platelets
- WBCs
where does erythropoietin come from? what is the process?
kidney
low arterial O2 level –> erythropoietin (a glycoprotein, major growth factor for RBCs, absence - severe anemia) –> bone marrow –> RBCs are produced –> kidney again
feedback cycle is disrupted by kidney or marrow disease, iron deficiency or an essential vitamin
what is the drug of recombinant erythropoietin?
Epoetin alfa - recombinant erythropoietin
In vials (2000 to 10,000 U/ml) for iv or sc administration
Normally given three times a week (t 1/2 10 h)
Iron stores should be sufficient, if not, iron dextran is given
The most common side effect - aggravation of hypertension, seen in 20% to 30% of patients - most often associated with too rapid a rise in hematocrit
No significant allergy reported
what’s the therapeutic use of epoeitin alfa?
Anemia of chronic renal failure
Anemias associated with surgery – reduces the need for blood transfusion
AIDS patients, especially those treated with zidovudine
Cancer chemotherapy
Anemia of prematurity and certain chronic inflammatory illnesses
Athletes use epoetin alfa to increase their hemoglobin level (“blood doping”). Misuse can cause death
whats the most common cause of anemia? what can this cause to happen’?
iron deficiency from lack of dietary iron.
leads to microcytic hypochromic anemia, affects iron-dependent enzymes (cytochrcomes, catalase, peroxidase, xanthine oxidase), also associated with learning problems in children.
who can store more iron in the body male or female?
males.
where is iron stored?
Excess iron (aggregated ferritin)
- known as hemosiderin
- constitutes about one third of iron stores
from here it goes to -
reticuloendothelial system (major iron store), hepatocytes.
from these two transferrin moves it to skeletal muscles and other body stores/organs.
Transferrin moves it between the two.
what are common causes for iron deficiency?
Inadequate iron intake (nutritional)
For growth in infants and children
Increased requirement in women (pregnancy, menstruation, lactation)
Malabsorption
Pathological blood loss (in men and post-menopausal women especially that from the gastrointestinal tract)
what are some iron treatment problems?
The ability of the patient to tolerate and absorb medicinal iron is important
Gastrointestinal tolerance to oral iron is limited- upset stomach -25% of people
Mainly absorbed only in the upper small intestinal (delayed-release preparations - usefulness?)
Side effects: Nausea, gastric discomfort, constipation, diarrhea
Heme iron better absorbed (as part of myoglobin)
Nonheme iron not well absorbed - bulk of dietary iron
What are iron salts?
Ferrous sulfate –least expensive – treatment of choice Other ferrous salts: fumarate gluconate succinate Ferrous salts are absorbed about three times as well as ferric salts
What is carbonyl iron?
Carbonyl iron: microspheres of pure iron
– less gastrointestinal toxicity than iron salts
FEOSOL caplets – 50 mg t.i.d.
What does vitamin C do for absorption? ascorbic acid? caffeine?
Vitamin C increases absorption
Ascorbic acid, 200 mg or more, increases absorption by 30%
increased incidence of side effects too
Caffeine reduces absorption
What is the iron therapy indicated?
Adults - 200 mg of iron / day
(65 mg three times a day)
Children - half the avg adult dose
(15 to 30 kg wt.)
Small children - 5 mg/kg and infants (can tolerate relatively large doses)
Pregnant women - 15 to 30 mg per day
(for prevention) (adequate to meet the 3-6 mg daily requirement of the last two trimesters)
Non-urgent - 100 mg (35 mg three times daily)
treatment of iron-deficiency anemia
What is parenteral iron
An effective alternative when oral therapy fails
Indications:
Malabsorption
Severe oral iron intolerance
As a routine supplement to total parenteral nutrition
In patients with renal disease, receiving erythropoietin
Side effects:
Acute hypersensitivity
Anaphylactic reactions - in 0.2% to 3% of patients
what are the ways of parenteral iron and what are they like?
Intravenous
Preferred
More reliable response
Intramuscular - more local side effects skin discoloration long-term discomfort concern about malignant change at injection site
what is megaloblastic (macrocytic) anemia?
RBCs – as large as the lymphocyte, fewer in number
Causes: Due to lack of
folic acid or
vitamin B12 (cobalamin)
Deficiency more common in older adults
Folate – food fortification – masks vit. B12 deficiency resulting in neurologic damage
In pregnancy - prevention of folate deficiency and permanent neural tube defects in children minimized
what is folate and vitamin B12 interaction?
Tetrahydrofolate is necessary for DNA synthesis
Cobalamin and folate are cofactors for tetrahydrofolate production
Deficiency of either impairs cell division in the bone marrow while RNA and protein synthesis continues – enlarged erythrocytes
Cobalamin deficiency – impairs synthesis of S-adenosylmethionine – necessary for proper nervous system functioning
what happens when B12 is malabsorbed?
Food vitamin B12 malabsorption: altered gastric acid secretion H2 blockers proton pump inhibitors colchicine neomycin aminosalicylic acid gastric surgery atrophic gastritis
But the patient can still absorb free vitamin B12.
food - meat, eggs and milk, Ingested vitamin B12 protein bound
pepsin and acid break it down to create free vitamin B12
free vitamin B12 binds to intrinsic factor from stomach parietal cells, and it is then absorbed from small intestine
where does pernicious anemia act in the B12 process?
pernicious anemia blocks intrinsic factor so free vitamin B12 can’t bind to it to be absorbed from the small intestine
what’s pernicious anemia caused by?
Injury to stomach parietal cells or autoantibodies
Lack of intrinsic factor – Vit. B12 not absorbed from the intestines
Given parenterally - by injection
Cyanocobalamin and hydroxocobalamin (only intramuscular formulation)
Never iv -anaphylaxis
how do you treatm Vit. B12 deficiency?
Replace liver stores and improve neurologic symptoms
Cyanocobalamin and hydroxocobalamin (only i.m. formulation)
Neurologic manifestations – 1000 µg im per day for 7 days then weekly for 1-2 mths
Alcohol reduces absorption
what is folic acid deficiency do?
Folic acid will supply folate needed for DNA synthesis
Anemia corrected
It DOES NOT correct the lack of methionine and
succinyl Co-A synthesis – this will cause neurological deficits
how does folic acid deficiency occur and what type of anemia can it cause?
Diet - Green vegetables, nuts, cereal, fruit, dairy products, yeast
Inadequate dietary intake
Increased demand in pregnancy and infancy
Impaired metabolism in alcoholics
Deficiency
Megaloblastic anemia
what is folic acid therapy?
Very important - rule out underlying vit. B12 (cobalamin) deficiency
In acutely ill – folate, pteroylglutamic acid injection (5 mg/ml) – 1-5 mg im
Upto 5 mg per day in malabsorption syndrome
1-2 mg orally - Folic acid (FOLVITE) oral tablets – 0.4, 0.8 and 1 mg of pteroylglutamic acid
what is folinic acid?
Folinic acid (leucovorin calcium, citrovorum factor)
- 5-formyl derivative of tetrahydrofolic acid
- More expensive than folic acid
what are pyrimethamine and trimethoprin and high-dose methotrexate?
folate antagonists inhibit dihydrofolate reductase