ANEMIA OF ABNORMAL IRON METABOLISM P1 Flashcards by Misaki Ayuzawa

RBC production is impaired ← LOW IRON (raw material)
RBC lifespan is shortened
frank loss of RBC from the body

ANEMIA

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when iron is the limiting factor

IRON RESTRICTED

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iron and heme are raw materials for HGB assembly
if iron and heme levels are low, there will be impaired RBC
production

ANEMIAS OF IMPAIRED PRODUCTION:

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Iron-Restricted Anemia:

○ Iron Deficiency Anemia
○ Anemia of Chronic Inflammation

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Sideroblastic Anemias

○ Acquired: Lead Poisoning
○ Hereditary: Porphyrias

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Iron Overload

○ Etiology
○ Pathogenesis
○ Lab Diagnosis
○ Treatment

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Inadequate production of protoporphyrin → diminished heme →
diminished hemoglobin, but with excess iron

SIDEROBLASTIC ANEMIA

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results when there is blockage of protoporphyrin production at various stages in the heme synthetic pathway leading to accumulation of porphyrins

Porphyrias

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excess accumulation without anemia

HEMOCHROMATOSES

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impaired iron kinetics
- ___________
-___________

IRON LOADING ANEMIAS
- Hemoglobinopathies
- Thalassemias

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Three Iron Compartments in Normal Humans

Functional Iron Compartment
Storage Iron Compartment
Transport Iron Compartment

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Compartment which hemoglobin iron is in the blood
Myoglobin iron in muscle and Peroxidase, catalase, cytochromes, riboflavin in all cells

Functional Iron Compartment

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Compartment which transferrin in plasma

Transport Iron Compartment

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Compartment which ferritin and hemosiderin are in macrophages and hepatocytes; small amounts except mature cells

Storage Iron Compartment

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Approximate Total Body iron of Functional, Storage and Transport

68, 10, 3
18
<1

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Typical Iron Content of Functional, Storage and Transport

2.400, 0.360, 0.120
0.667
0.001

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Ferroportin transport three

enterocyte
macrophage
hepatocyte

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Reference Interval of Assay in Male
ESR Male - ____________
Serum Iron - ____________
Total Binding Iron Capacity - _________
Transferrin Saturation - ___________
Serum Ferritin, Male - _____________
Serum Ferritin, Female - _____________

0-15, 0-20
50-160
250-400
20-55
40-400
12-160

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Reference Interval of Assay in Male
ESR Female - ____________
Serum Vitamin B 12 - ________
Serum Folate - __________
RBC folate - __________
Haptoglobin -_______
Free Serum Hemoglobin -__________

0-20, 0-30
200-900
>4.0
>120
30-200
0-10

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____________develops when the intake of iron is
inadequate to meet a standard level of
demand

Iron Deficiency Anemia

when the need for iron expands without
compensate intake:
1. ___________
2. _______________
3. ___________
4. ___________

Inadequate Intake
Increased need relative to Iron supply
Impaired Absorption
Chronic loss of hemoglobin

INADEQUATE INTAKE:
- each day, _______of iron is lost from the body
-_________________
-________________
body conserves all iron from ______________
daily requirement of _________ of iron from the
diet maintains iron balance

1 mg
- mitochondria of desquamated skin
- sloughed intestinal epithelium
senescent cells
1 mg

INADEQUATE INTAKE:
If iron in the diet is consistently inadequate,
body’s stores of iron becomes __________
_____________ in order to manage
the iron needs for other body cells
- __________ becomes apparent when the
production rate is insufficient to replace
lost cells

depleted over time
RBC production slows
Anemia

INCREASE NEED RELATIVE TO IRON SUPPLY
- Periods of rapid growth
- _____________
-____________
-____________
- both _____________ need ___________ of
iron BUT its much higher amount per kg of
body weight for the __________

Infancy
Childhood
Adolescent
infants and adult men - 1 mg/day - infant

INCREASE NEED RELATIVE TO IRON SUPPLY EPO Treatment - _______________ -______________

- rapid expansion of erythron - demand for iron is great but iron cannot be mobilized fast enough Functional Iron Deficiency

__________________ - Adequate diet but inability to absorb that iron - Pathologic: _____________ - Inherited mutations in iron regulatory proteins: ___________: lead to a persistent production of hepcidin → inactivate ferroportin in the enterocyte → prevent iron absoption in the intestine

Impaired Absorption Celiac disease Matriptase-2 Protein

IMPAIRED ABSORPTION - decrease stomach acidity → decrease conversion of dietary ferric to absorbable ferrous iron -_____________ -___________ -___________ - some drugs bind to iron in the intestine → decrease absorption

aging - bariatric surgery - acid reducer medications

________________________ - Repeated blood donations -___________ (Gastrointestinal, genitourinary) - __________ heavy menstrual bleeding - hemolysis - _________develops when iron loss exceeds iron intake over time and the storage iron is exhausted

Chronic blood Loss Hemorrhage Menorrhagia Anemia

Laboratory Test Values in Pathogenesis Hemoglobin - __________ Serum Iron - _____________ TIBC -_____________ Ferritin -___________ Stfr - ___________ Hemoglobin Content of Reticulocytes-______________

N N⬇️ N ⬇️ ⬇️ N⬆️⬆️ ⬇️ ⬇️⬇️ ⬆️⬆️⬆️ N ⬇️ ⬇️

Latent Iron Deficiency -_________________ -________________ Iron Deficiency Anemia -_____________________

Storage Iron Compartment Transport Iron Compartment Functional Iron Compartment

EPIDEMIOLOGY - ___________________ high risk - monthly loss of blood increases their routine need for iron (met with standard US diet) -_________________ increase iron needs associated with growth - Women in childbearing age: - _______________can lead to a loss of nearly ________________→ depletes iron

Menstruating women: Adolescent girl: Women in Childbearing age pregnancy and nursing 1200 mg of iron

EPIDEMIOLOGY - _______________: growth requires iron for the cytochromes of all new cells - worsens with dietary inadequacies especially in poverty or neglect - Rare in ________________ and __________: - body conserves iron so tenaciously - only lose about 1 mg/day

Growing Children men and postmenopausal women

EPIDEMIOLOGY - ________________ - ulcers, tumors, hemorrhoids should be suspected especially if the diet is known to be adequate in iron - ________________ → gastritis and chronic bleeding

Gastrointestinal disease Regular aspirin ingestion and alcohol consumption

EPIDEMIOLOGY - ____________ - poor diet - loss of gastric acidity → impair absorption - ______________________ - worm attaches to the intestinal wall and literally sucks blood from the gastric vessels -___________________ - heme iron is lost due to intestinal or urinary bleeding

Elderly Hookworms: N. americanus, A. duodenale Other Parasites: T. trichiura, Schistosomas

-____________________- prolonged maneuvers → IDA - Exercise-induced hemoglobinuria aka March hemoglobinuria - RBCs are hemolyzed by foot-pounding trauma → iron is lost as Hgb in the urine - if recurrent and severe → anemia

Soldiers and long-distance runners:

LABORATORY DIAGNOSIS - ___________ - can be detected with tests such as __________ - NOT part of comprehensive screening test - progressing iron deficiency can go undetected - __________ - standard _____________ → prompt additional testing

Early stages - ferritin; not part of test Late stages - CBC parameters fall; prompt additional test

LABORATORY DIAGNOSIS - Categories: - ___________ - ___________ -_____________

LABORATORY DIAGNOSIS - Categories: - screening - diagnostic - specialized

Screening for IDA decrease Hgb concentration -____ RDW precede the decrease Hgb - progressive decline of RBC indices → microcytosis and hypochromia - RBC ct becomes decrease slowly - ________ apparent early but not a prominent finding -___________ may be present but no shape is characteristic - ________ present especially if IDA results from chronic bleeding - ____ are typically normal

>15% Polychromasia: Poikilocytosis Thrombocytosis WBC

Diagnostic Testing for IDA -____________ remain the backbone for diagnosis of iron deficiency - Assays: - ____________: measure of the amount of iron bound to transferrin (transport iron) in the serum - _________: indirect measure of transferrin and the available binding sites for iron -_____________ % of transferrin binding sites occupied by iron → calculated (next slide) - _____________ intracellular storage repository for metabolically active iron

Biochemical iron studies Serum iron TIBC Transferrin saturation: Serum ferritin:

Specialized tests for IDA - not commonly used for the dx of iron deficiency - show abnormalities that become important in the differential diagnosis of similar conditions - accumulated porphyrin precursors to heme are elevated - ________________ accumulates when iron is unavailable - chelates with zinc → ______________ - assayed fluorometrically - _____________can be assayed using immunoassays - levels decrease as the disease progresses - cells seek to take in as much iron as possible

Free erythrocyte protoporphyrin (FEP) zinc protoporphyrin (ZPP) Soluble transferrin receptors (sTfR)

bone marrow assessment is NOT indicated for suspected uncomplicated iron deficiency - routinely performed when BM specimen is collected for other reasons - Iron Deficiency in BM: - Early: ___________, decrease M:E ratio due to increase erythropoiesis - Progression: ___________ subsides; deficient iron leads to slowed RBC production - polychromatic normoblasts - Therapeutic trial of iron provides a less invasive and less expensive diagnostic assessment

hyperplastic hyperplasea

Specialized tests for IDA -_______________ show the most dramatic morphologic changes ___________ lagging behind nuclear maturation - cytoplasm remains ________ after the nucleus has begun to condense. - cell membranes appear irregular and are usually described as “______” - ______________ provides a less invasive and less expensive diagnostic assessment

polychromatic normoblasts - Nuclear-cytoplasmic maturation bluish shaggy Therapeutic trial of iron

Treatment - treat underlying contributing cause (e.g. hookworms, tumors or ulcers.) - ___________________ - for simple nutritional deficiencies or increase need -_____________________: standard prescription - side effects: __________ → leads to poor compliance - Course of tx: ___________

Dietary Supplementation Oral supplementation of ferrous sulfate nausea, constipation 6 months or longer

Treatment - _________________- provide iron supplementation has been studied in developing nations - reduced intestinal side effects compared to ferrous sulfate but equally effective in correcting iron-deficiency

Oral bovine lactoferrin

__________________________ - used in rare cases in which iron absorption is impaired -________________ -______________ -_______________ causing iron-refractory iron deficiency anemia or IRIDA) - but with notable side effects - ______________: rarely warranted because of associated risk UNLESS the HGB is dangerously low

intravenous administration of iron dextrans - gastric achlorhydria - celiac disease - matriptase-2 mutations RBC transfusions

HGB content of reticulocytes will correct within _______ - Retic ct begin to increase within ___________ - anticipated rise in HGB appears in ___________ - levels return to normal ny about ___________ - ____________still reflects microcytic RBC population for several months with younger normocytic cells (biphasic population) - Iron therapy must continue for another ____________ to replenish the storage pool and prevent relapse

2 days 5-10 days 2-3 weeks 2 months PBS and indices 3-4 months

Response to Treatment - if still unresponsive despite the iron supplementation → ________________-

consider further investigation