Exam 3 Iron/Porphyrin/Trace Elements Flashcards
Distribution & function of iron throughout the body
- Hemoglobin 65% - oxygen delivery
- Myoglobin 10% - muscle oxygen
- Bound to enzymes 1-3% - cellular oxidative mechanism
How much iron does the body contain?
3-5g
Types of iron
• Heme – meats, especially organ meats
• Non-heme – plants & iron-fortified foods
o Spinach, beets, beans, almonds, bran flakes
Where is iron stored?
• Stored in bone marrow, spleen, liver
What are the storage forms of iron?
• Ferritin – soluble
1. Major iron storage protein found in all cells in body
2. Protein shell surrounding iron core
• Hemosiderin – insoluble
1. Found in cells of liver, spleen, bone marrow
How is iron transported?
• Plasma: transferrin
- Formed in liver
- Transports Fe3+ from GI tract and delivers to specific receptor sites
Iron RDA - ages 19-50
18mg/d
Iron RDA - ages 51+
8mg/d
Describe ferrous iron
2+
- absorbed form
- bound to protein: transferrin
Describe ferric iron
3+
- not easily absorbed
- dietary form
- needs to be reduced before it can be absorbed
- transport & storage form
What causes decreased levels of iron?
• Decreased availability o Inadequate intake, malabsorption • Increased need o Growth, premenopausal women, pregnancy • Chronic loss o Peptic ulcer, excessive menstruation, hemorrhoids, gastritis • Chronic diseases o Infections, inflammatory diseases
What causes increased levels of iron?
• Increased absorption
o Hemochromatosis, medication/iron supplements, dietary intake, transfusion
• Increased RBC destruction
• Disease
o Lead poisoning, pernicious anemia, megaloblastic anemia
What causes iron deficiency anemia?
Blood loss, inadequate intake, malabsorption
Describe transferrin, % saturation, and ferritin in IDA
Transferrin - increased
% saturation - decreased
Ferritin - <10ng/mL typical
Who is affected by IDA?
Children, women, pregnant women
What is hemosiderosis?
Secondary/acquired iron accumulation
No tissue damage, reversible
What causes hemosiderosis?
Iron supplements, blood transfusions
What is hemochromatosis?
- Hereditary disorder: mutation in HFE gene
- Iron accumulates in tissues leading to organ failure
- Irreversible
Symptoms of hemochromatosis
- Diabetes mellitus
- Bronzing of skin
- Sexual dysfunction
- Fatigue, weakness
- Manifests in middle age
What is a total iron test?
Reflects amount of ferric Fe3+ iron bound to transferrin
- Does not include free iron found in hemoglobin
What is TIBC test?
Amount of iron that could be bound if transferrin were saturated
- Typically, 1/3 of iron-binding sites are saturated
What is % saturation?
Transferrin saturation
- Normal range 15-50%
What is transferrin?
Negative-acute phase reactant
- Useful to diagnose hypo chromic anemias
- Measured by the amount of iron it can bind
What is ferritin?
Best diagnostic test for IDA
- Reflects iron stores
- Serves as acute-phase reactant
- Patients with inflammation or chronic infection may have increased ferritin
Specimen requirements for iron studies
- Serum or plasma with heparin
- Oxalate, citrate, or EDTA binds Fe ions
- Early morning sample preferred due to diurnal variation (highest am)
- No hemolysis
Test methodology for iron
Colorimetric
Iron reference range - men
65-175 ug/dL
Iron reference range - women
50-170 ug/dL
Transferrin reference range
200-360 mg/dL
Ferritin reference range - male
20-250 ng/mL
Ferritin reference range - female
10-120 ng/mL
TIBC reference range
250-425 ug/dL
Calculation for TIBC
TIBC = Iron + UIBC (unsaturated iron binding capacity)
Calculation for transferrin
Transferrin mg/dL = TIBC x 0.70
Calculation for % saturation
% sat = (total iron/TIBC) x 100
What is decreased in IDA?
Iron, ferritin, % saturation
What is increased in IDA?
Transferrin, TIBC
What is increased in iron overdose?
iron, ferritin, % saturation
What is decreased in iron overdose?
transferrin, TIBC
What is increased in hemochromatosis?
Iron, ferritin, % saturation
What is decreased in hemochromatosis?
transferrin, TIBC
What is decreased in malnutrition?
iron, transferrin, ferritin, TIBC
- % sat. variable
What is decreased in chronic anemia?
iron, transferrin, % saturation, TIBC
What is increased in chronic anemia?
ferritin
What is increased in acute liver disease?
iron, ferritin, % saturation
- TIBC, transferrin variable
Describe the structure & function for porphyrins
- Chemical intermediates in the synthesis of hemoglobin, myoglobin, & various enzymes
- Made up of four pyrrole rings
Where are porphyrins synthesized?
Bone marrow & liver
- Synthesis occurs in mitochondria/cytoplasm
What is hemoglobin made of?
4 heme + 4 polypeptide chains
What is myoglobin made of?
1 heme + 1 polypeptide chain
What are porphyrias?
• Disorder of porphyrin metabolism
- Inherited: rare
- Acquired: lead
Symptoms of porphyrias
- port wine colored urine
- cutaneous photosensitivity
- itchy skin
- hyperpigmentation
- inflammatory reaction occurs on exposure to UV light
- neurologic abnormalities
What is uroporphyrin found?
urine
Where is coproporphyrin found?
urine & feces
Where is protoporphyrin found?
feces
Specimen requirements for porphyrins
• Protect specimens from light • Blood – whole blood & plasma • Test methods: Urinary porphobilinogen (PBG) Urinary aminolevulinic acid (ALA) Urinary porphyrins
What does lead interfere with?
- Interferes with heme synthesis
* Inhibits ALA dehydrates and ferrochelatase
Final storage site for lead?
Bone 95%
Specimen requirements for lead
• Whole blood
Circulating lead found in RBCs
o Royal blue top with EDTA anticoagulant
o Lead free collection tubes
ULN for lead, children
<10 ug/dL
ULN for lead, adults
<25 ug/dL
Symptoms of lead exposure
Headaches, clumsiness, seizures, hyperactivity, ADHD, decreased IQ, abdominal pain, anemia
Basophilic stippling
What are essential trace elements?
considered essential if a deficiency impairs a biochemical or functional process
Examples of essential trace elements
Iron, copper, zinc, selenium, chromium, manganese
Function of copper
Critical for iron reduction in heme synthesis pathway
Causes & consequences of copper deficiency
- Malnutrition
- Malabsorption
- Neutropenia & hypochromic anemia
- Osteoporosis
- Decreased pigmentation of skin
What is Menkes disease?
Genetic disease that results in extreme deficiency of copper
What is Wilson’s disease?
Genetic disease that results in copper toxicity
- Kayser-Fleischer rings
Function of zinc
- Influences more than 300 enzymes
- Synthesis & metabolism of proteins, glycolysis, cholesterol metabolism
Consequences of zinc deficiency
- Causes growth retardation
- Slow skeletal maturation
- Testicular atrophy
Toxicity of zinc
- GI tract symptoms
- decreased heme synthesis
Where is aluminum found?
antacids, astringents, buffered aspirin
Symptoms of aluminum toxicity
gait disturbances, seizures, dementia, bone disease, anemia
Where is arsenic found?
environmental/occupational exposure
Symptom of increased arsenic
Increased frequency of skin cancer
Where is cadmium found?
inhaled in tobacco smoke, ingested in food, airborne exposure
Symptoms of increased cadmium
o Chronic exposure – renal dysfunction
o Breathing vapors – nasal epithelial & lung damage
o Nausea, vomiting, abdominal pain
Symptoms of increased mercury
headache, tremors, cramps, diarrhea, impaired coordination, dermatitis, proteinuria, hepatic dysfunction
