11 - Nutritional Anemias Flashcards
1
Q
Iron Functions in the body
A
- Hemoglobin
- Myoglobin
- Cellular enzymes
- Electron transport (aerobic respiration)
2
Q
Dietary Iron Sources
A
- Animal sources - heme; ferrous (2+) iron
- Liver, mollusks, beef, shrimp, sardines, turkey
- Plant sources - non-heme; ferric (3+) iron
-Enriched cereals/pasta, beans, lentils, pumpkin
seeds, blackstrap molasses
3
Q
Iron Absorption
A
- Absorbed in duodenum and proximal jejunum
- Enhanced by acidity
- Ascorbic acid increases the absorption of non-heme
iron - Heme iron is absorbed more efficiently than non-
heme iron - 10-15% of total iron intake is in heme form and 85-
90% in non-heme. - Molecules involved in absorption
- Heme transporter
- Duodenal cytochrome B
- Divalent metal transporter 1 (DMT1)
- Ferroportin 1
- Hepcidin
- Hephaestin
- Transferrin
4
Q
Iron Distribution
A
- Red blood cells – 65%
- Storage – 30%
- Myoglobin – 3.5%
- Enzymes – 0.5%
- Transferrin-bound – 0.1%
5
Q
Storage of Iron/Iron carriers in the body
A
- Ferritin – organized, globular protein complex, readily
mobilized iron, also in circulation - Hemosiderin – disorganized, insoluble, less able to
mobilized, stain with Prussian blue
6
Q
Iron Uptake by Cells mechanisms
A
- Surface transferrin receptors
- Endocytosis by clathrin-coated pits
- Release of iron to cytoplasm (DMT1)
- Recycling of transferrin receptor and transferrin
7
Q
Iron Deficiency effect
A
- Interference with heme synthesis
- Decreased intracellular hemoglobin
- Microcytic, hypochromic anemia
- Causes: Chronic bleeding – gyne, GI, GU
Malabsorption, gastric bypass
Vegetarian - diet
8
Q
Iron Deficiency - Clinical Findings
A
- Weakness, fatigue, headache, difficulty with
concentration, angina, myalgias - Pica (craving for non-nutritive substances)
- Brittle nails/hair
- Atrophic tongue
- Cheilosis
- Koilonychia
9
Q
Sequential Iron Changes
A
- Iron depletion
- Iron deficient erythropoiesis
- Iron deficiency anemia
10
Q
Morphology of Iron Deficiency
A
- Blood
- Microcytic, hypochromic anemia
- Anisopoikilocytosis with ovalocytes, “pencil” cells
- Low reticulocyte count
- Bone marrow
-Poorly-hemoglobinized erythroid precursors with
“ragged” cytoplasm - Absent stainable iron
11
Q
Iron deficiency - Laboratory findings
A
- Iron studies
– Decreased serum iron - Increased total iron binding capacity (TIBC)
- Decreased % saturation
- Decreased ferritin (acute phase protein)
- Increased soluble transferrin receptors
- Increased free erythrocyte protoporphyrin
- Increased zinc protoporphyrin
12
Q
Iron Deficiency Treatment
A
- Identify source of iron deficiency
- Oral ferrous iron (ferrous sulfate)
- every other day
- correction of CBC in 3 months
- Continue for 6 months
- Intravenous iron
- Only in selected cases (malabsorption, compliance)
- Risk of allergic reaction
13
Q
Hereditary Hemochromatosis (HH)
A
- HFE gene mutation (chromosome 6) (C282Y, H63D)
- Autosomal recessive
- 10% Europeans are carriers, 0.25-0.5% affected
- Other mutations (juvenile hemochromatosis):
- Hepcidin gene
- Hemojuvelin gene
14
Q
Hereditary hemochromatosis Pathophysiology
A
- Down regulation of hepcidin synthesis
- Dysregulation of ferroportin
- Increased iron absorption and release from storage
sites - Full saturation of transferrin
- Increased accumulation of parenchymal iron
- Toxic cell injury
15
Q
Hereditary hemochromatosis - Clinical Findings
A
- Presentation between age 40-60 (men > women)
- End-organ damage
- Cirrhosis
- Bronze diabetes
- Heart failure
- Testicular atrophy
- Amenorrhea
- Arthropathy
16
Q
Hereditary Hemochromatosis - Lab Findings
A
- Liver biopsy – increased parenchymal iron (replaced
by MRI) - Iron studies
– Increased serum iron - Decreased total iron binding capacity (TIBC)
- Increased % saturation
- Increased ferritin
17
Q
Hereditary Hemochromatosis - Treatment
A
- Weekly phlebotomy
- Chelation therapy
- SQ/IV
(deferoxamine/Desferal) - Oral (Deferiprone/Ferraprox,
Deferasirox/Exjade, Jadenu)
18
Q
Hemosiderosis
A
- Secondary iron overload
- Multiple transfusions (250 mg iron per unit)
- Chronic alcohol use
- Ineffective erythropoiesis (thalassemia major)
- Iron accumulates in macrophages and Kupffer cells
(rather than parenchymal cells) - Less cell toxicity and organ damage
19
Q
Anemia of Chronic Disease (ACD)
A
- Chronic inflammatory, infectious, or neoplastic
disease - Upregulation of hepcidin (acute phase protein)
- interferes with iron release from cells
- “functional” iron deficiency
- Blunted erythropoietin synthesis
- Impaired erythropoietin binding to erythroid
precursors
20
Q
Anemia of Chronic Disease - Laboratory findings
A
- Mild-moderate normocytic/microcytic anemia
- Normal red cell morphology (normal RDW)
- Iron studies
– Decreased serum iron - Decreased total iron binding capacity (TIBC)
- Decreased normal % saturation (variable)
- Increased ferritin
- Increased C-reactive protein and sedimentation rate
21
Q
difference between anemia of chronic disease and iron-deificiency anemia
A
22
Q
Sideroblastic Anemia - appearance and basis
A
- Ringed sideroblasts
- Impaired iron incorporation into heme
-Abnormal erythroid precursors with excess iron in
mitochondria
- Perinuclear “ring-like” distribution
23
Q
Sideroblastic Anemia - genetic and acquired
A
- Inherited
- δ-aminolevulinate synthase 2 (heme synthesis)
- Acquired
- Chronic alcohol use
- Pyridoxine deficiency
- Lead poisoning
- Copper deficiency
- Drugs (isoniazid, chloramphenicol)
- Myelodysplastic syndromes
24
Q
Sideroblastic Anemia - Laboratory Findings
A
- Moderate-severe microcytic anemia
- Dimorphic red cell population
- Basophilic stippling, Pappenheimer bodies
- Iron studies
– Increased serum iron - Decreased total iron binding capacity (TIBC)
- Increased % saturation
- Increased ferritin
25
Sideroblastic Anemia Treatment
* High dose pyridoxine (some cases respond)
* Transfusion support
* Bone marrow/stem cell transplant (congenital cases)
26
B12 and folic acid
* Prevalence of B12 deficiency is 1-2% in the general population and 10-15% in older and
hospitalized people.
* Total body stores of vitamin B12 are in the range of 2 to 5 mg, with approximately half of this
stored in the liver. If vitamin B12 intake or absorption ceases, deficiency typically does not
develop for at least one to two years, sometimes longer.
* Folate acid deficiency is uncommon in people eating a varied diet and is added to many
prepared foods.
* Total body folate stores are estimated to be approximately 500 to 20,000 mcg (0.5 to 20 mg).
If folate intake ceases, deficiency may develop within weeks to months, or more rapidly if
demands for folate are increased.
* Testing includes: CBC and smear, serum B12 and folate levels to start.
* Autoantibodies to intrinsic factor – obtain if no other cause for deficiency, as the diagnosis of
pernicious anemia
* Consider MMA (methyl malonic acid) and homocysteine for patients whose initial tests are
borderline .
MMA and homocysteine NML – no deficiency
MMA and homocysteine elevated – B12 deficient but does not exclude folate deficiency
MMA NML and homocysteine elevated – folate deficiency
27
cobalamin processing in the body
28
methionine and folate cycle
29
B12, methylmalonic acid, and folic acid
30
causes of b12 deficiency
31
causes of folic acid deficiency
32
Changes in erythrocytes with B12 or folate deficiency - megaloblastic
33
treatment of b12 deficiency in adults
34
treatment of folic acid deficiency
Give the patient 1-5 mg PO daily
Tell them to eat a better diet
(bean, eggs, and leafy greens)
