Anemia Flashcards
Most of the iron in the body is in (1)
- hemoglobin.
What are the two forms of iron available in the diet?
heme iron (found in meat, fish & poultry), which has the greatest bioavailability and nonheme iron (found in vegetables & dietary supplements)
Absorption of nonheme iron is affected by?
(a) phosphates which decrease absorption; and,
(b) ascorbic acid and meat which increase absorption.
Iron is best absorbed in its (1) form, however, dietary iron is in the (2) form which is not absorbed. (2) is ionized by stomach acid and then reduced to the (1) form.
- ferrous (Fe2+)
2. ferric (Fe3+)
The ferrous form is actively taken up primarily in the (1) but absorptive processes of the mucosa limit the amount of iron absorbed.
- duodenum
Within the mucosal cells, ferrous iron is oxidized to ferric iron which forms a complex with (1), a ß1-glycoprotein with two binding sites for ferric iron.
- transferrin
This complex binds to specific receptors in the plasma membrane and is taken up by receptor-mediated endocytosis.
ferric iron and transferrin complex
If iron is plentiful, then there are fewer (1) on the surface of cells. This prevents iron-replete cells from
receiving excess iron
- transferrin receptors
combination of ferric iron with apoferritin
ferritin
aggregated ferritin
hemosiderin
Sites of iron storage include:
(1) the reticuloendothelial system
(2) hepatocytes.
Storage forms of iron include:
hemoglobin, myoglobin, enzymes, ferritin, hemosiderin
Symptoms of iron deficiency anemia
a. Feelings of weakness and lassitude
b. Headache
c. Dizziness
d. Palpitations; chest pain
e. Decreased exercise tolerance; shortness of breath
Iron deficiency diagnosis
quantitation of transferrin saturation,
and plasma ferritin
Adverse effects of oral iron
(a) heartburn
(b) constipation or diarrhea
(c) nausea (more prevalent at higher doses)
(d) upper abdominal pain (more prevalent at higher doses)
hemoglobin recovers in 1–2 months
ferrous sulfate
Contraindications of oral iron
antacids, proton-pump inhibitors, H2-
receptor antagonists decrease absorption
replenishment of iron stores may require many (3–6) months
ferrous sulfate
can interfere with absorption of many drugs; Avoid
concurrent administration, separate doses by >2 hours.
ferrous sulfate
Clinical uses of parenteral iron
(a) Patients in whom GI absorption is prevented by disease
(b) Patient who cannot tolerate orally administered iron
(c) Hemodialysis patients (Sodium ferric gluconate and iron
sucrose)
complex of ferric oxyhydroxide with polymerized
dextran
Iron dextran
The complex must be phagocytized by reticuloendothelial
cells before iron becomes available
Iron dextran
Can cause anaphylaxis
Iron dextran
Lower risk of anaphylactic reactions
Sodium Ferric gluconate and iron sucrose
Delivered to transferrin more readily
Sodium Ferric gluconate and iron sucrose
Signs and symptoms of iron poisoning
i) abdominal pain
ii) diarrhea
iii) vomiting brown or bloody stomach contents with pills
iv) lassitude & drowsiness
v) pallor or cyanosis
vi) hyperventilation (due to acidosis)
vii) cardiovascular collapse
viii) Death can occur within 6 hours or be delayed 12-24 hours
with a period of apparent recovery in between
Iron poisoning treatment
Treatment includes emesis & lavage with sodium bicarbonate to precipitate iron
If plasma concentration of iron > 3.5 mg/L, (1) (IM or IV) is indicated.
- deferoxamine
has a high affinity for ferric iron. Once bound with iron, excreted in the urine
Deferoxamine has a high affinity for ferric iron. Once bound with iron, feroxamine is excreted in the urine
Deferoxamine contraindications
Contraindicated in renal insufficiency and anuria
can cause allergic reactions (pruritus, wheals,
rash, anaphylaxis)
Deferoxamine
Without vitamin B12, folate is trapped as (1),
and subsequent steps in folate metabolism that require (2) are deprived of substrate. This provides the common basis for the development of (3) with deficiency of either vitamin B12 or folic acid
- methylTHF
- THF
- megaloblastic anemia
Deficiency in either of these substances results in defective synthesis of DNA in any cell attempting chromosomal repair or division.
Vitamin B12 and folic acid
important for folate metabolism and for the formation of methionine and S-adenosylmethionine from homocysteine
Methylcobalamin (CH3B12)
one of the two active coenzyme forms of B12
required for the isomerization of L-methylmalonyl CoA to succinyl CoA.
Deoxyadenosylcobalamin
one of the two active coenzyme forms of B12
released from digested
protein by the actions of gastric
acid and pancreatic enzymes
B12
Intrinsic factor, secreted from
(1) binds B12
- parietal cells
The complex interacts with
specific receptors on (1)
mucosal cells, is absorbed and
enters the circulation
- ileal
refers to IF-B12 complex
Once absorbed, B12 binds with (1) for transport to tissues. The complex is preferentially distributed to the (2) (up to
90%)
- transcobalamin II (TcII)
2. liver
Most circulating cobalamin is bound to ?
transcobalamin I and III
An alternate pathway for absorption exists which does not require intrinsic factor or an intact terminal ileum. The pathway involves (1) and accounts for 1% of ingested B12.
- passive diffusion
Deficiency (takes several years to develop following vitamin deprivation due to enterohepatic circulation
vitamin B12
Effects of B12 deficiency
a. Megaloblastic anemia
b. Potentially irreversible nerve damage:
parethesias of the hands and feet, decreased vibration and position senses with resultant unsteadiness, decreased deep tendon reflexes
In later stages: confusion, moodiness, loss of memory, and loss of central vision.
Diagnosis of B12 deficiency
a. Determination of the plasma concentration of B12
b. Examination of blood smear for macrocytosis and hypersegmented polymorphonuclear leukocytes
Clinical use: patients with pernicious anemia or ileal disease
Cyanocobalamin parenteral
Clinical use: In patients with pernicious anemia high doses are used since it is absorbed via passive diffusion
Cyanocobalamin (oral)
Plasma becomes normoblastic after 7 days
Cyanocobalamin
Are neuropsychiatric signs of B12 deficiency reversible?
They can be reversible with cyanocobalamin treatment if they are LESS than 6 months duration. Will need to keep pt on Therapy for at least 6 months to see improvement
Inadequate secretion of intrinsic factor
pernicious anemia
reduced to tetrahydrofolic acid
which acts as an acceptor of
one-carbon units
folic acid
Polyglutamates in food are hydrolyzed, reduced, & then methylated by (1). (2) is transported to tissues and is taken up by receptor-mediated endocytosis
- dihydrofolate reductase
2. methyl-THF
acts as a methyl donor (for formation of CH3B12) and as a
source of THF
Methyl-THF
The (1) reduces & methylates folic acid (PteGlu) and transports (2) into the bile for reabsorption by the gut
- liver
2. CH3THF
Folate is stored within cells as (1)
- polyglutamates
The principal effect of folic acid deficiency is:
a. Megaloblastic anemia
b. Unlike B12 deficiency, neurological abnormalities are NOT common
c. Folate deficiency during pregnancy is associated with congenital neural tube defects
Diagnosis of folic acid deficiency
a. Determining plasma concentration of folate
b. Examination of blood smear
prophylactic administration when there is
increased utilization such as in pregnancy and lactation
folate
circumvents the action of inhibitors of dihydrofolate reductase and potentiates the cytotoxic effects of 5-
fluorouracil
Leucovorin (folinic acid)
Folate deficiency during pregnancy is associated with ?
congenital
neural tube defects
High doses counteract the effects of antiepileptic drugs
Folic acid
Acute or chronic alcoholism
causes of folic acid deficiency
Inhibitors of dihydrofolate reductase (methotrexate, trimethoprim)
causes of folic acid deficiency
Drugs which interfere with absorption and storage of folate (certain anticonvulsants and oral contraceptives)
causes of folic acid deficiency
