Iron, Hemoglobin, and Porphyrins

Explain physiological function and distribution of iron

Human body has 3 to 5 grams

Vital role: Carry Oxygen

Component of: Hemoglobin (transport oxygen from the lungs to the rest of the body) and Myoglobin (store and provide oxygen spec. to muscle tissue)

Hemoglobin - 2.5

Stored forms - 1.0 as ferritin long term to hemosiderin

Myoglobin - 0.130 grams

Plasma - 0.035 grams

Enzymes - 0.015 grams

Explain the regulation of iron within the body

1. Small intestine - 10% absorbed, ferric state to absorbable ferrous state by redox reactions in stomach

Things that might stop this are: high gastric pH and excessive dairy intake (chelate iron by proteins)

Hepcidin is a critical regulatory protein produced by the liver that inhibits iron absorption in the small intestine

Describe the clinical utility for each of the following tests

Serum Iron

• measures the total amount of iron currently in circulation

Serum Ferritin

• measures the amount of iron held in storage form

Total Iron Binding Capacity

• measures the maximum amount of iron that transferrin can carry; measures the total amount of transferrin protein present

%Transferrin Saturation

• Serum Iron / TIBC x 100

• How much of the available transferrin is actually "filled" with iron

State the etiology and alteration in iron metabolism that occurs in

Iron deficiency anemia

1. Etiology

   1. Interference with intake

   2. Malabsorption

   3. Regulatory FActors

   4. Iron loss

2. Alteration

   1. Iron Depletion - The body's iron stores, measured as ferritin, are depleted and decreased

   2. Iron deficiency erythropoiesis - insufficient iron to insert into the protoporphyrin ring of heme, which results in decreased heme synthesis

   3. Iron deficiency anemia - Ineffective erythropoiesis causes a reduction in hemoglobin and red blood cells - hypochromic and microcytic cells

Clinical Indicator

• Serum iron is low

• TIBC is high

• Decreased %transferrin

• Serum ferritin is low

• Serum ferritin is high

Hemochromatosis

1. Etiology and alteration

   1. Increased accumulation of iron

   2. Excess iron goes to various organs and then inhibits organ function, causing hyperpigmented skin

Clinical Indicator

• Serum iron is high

• Serum ferritin is high

• TIBC is low

Anemia of chronic disease

1. Etiology

   • chronic infections and inflammatory disorders

2. Alteration

   • up-regulation of hepcidin

   • inhibition of absorption

   • sequestration of iron

Clinical Indicator

• Serum Iron is low

• TIBC is low

• Serum ferritin is normal to elevated

lead poisoning

1. etiology

   • basophillic stippling, lead incorporated into heme molecule instead of iron results in non-functional heme molecule

2. Alteration

   • lead competes with iron to bind to heme molecules

Sideroblastic anemia

1. etiology

   • Because of the synthesis defect, iron cannot be added to the protoporphyrin ring to form hem - Δ-Aminolevulinic Acid Synthase (ALA Synthase)

2. Alteration

   • the iron builds up within the mitochondria of developing cells

Clinical Indicator

• Serum iron is high

• Serum feritin is high - pappenheimer bodies

• TIBC is normal to low

List the steps of the heme synthetic pathway - including the intracellular location of different reaction steps along with the rate limiting reaction

1. Rate-limiting step - mitochondria

   1. Reaction: Succinyl CoA and Glycine are bound together.

   2. Enzyme: delta-aminolevulinic synthetase (ALA Synthetase).

   3. Product: delta-aminolevulinic acid (dALA)

2. dALA - Cell cytoplasm

   1. Step 2: Two dALA molecules are bound by ALA dehydratase to form Porphobilinogen.

   2. Step 3: Four porphobilinogen molecules are bound by Porphobilinogen deaminase to form Hydroxymethyl bilane.

   3. Step 4: Hydroxymethyl bilane is converted to Uroporphyrinogen III by the enzyme Uroporphyrinogen III synthetase.

   4. Step 5: Uroporphyrinogen III is converted to Coproporphyrinogen III by Uroporphyrinogen III Decarboxylase.

   5. Step 6: Coproporphyrinogen III is converted to Protoporphyrinogen III by Coproporphyrinogen III oxidase

3. Proroporphyrinogen III - back to mitochondria

   1. Step 7: Protoporphyrinogen III is converted to Protoporphyrin IX by the enzyme Protoporphyrinogen III oxidase.

   2. Step 8 (Final Step): The enzyme Ferrochelatase adds iron to Protoporphyrin IX to create Heme

4. Heme - back into the cytoplasm

   1. To form functional hemoglobin

Define porphyria

heterogeneous group of disorders characterized by enzyme deficiencies or dysfunctions that occur along the heme synthesis cycle

Compare and contrast primary and secondary porphyrias

Both:

• Photosensitivity, itchy skin, hyperpigmentation, and inflammatory reactions when exposed to UV light

• Vampire phenomenon

• Port wine colored urine

• Classified as hepatic or erythropoietic

Contrast

Primary

• Inherited

• ALAD Porphyria

• Acute Intermittent Porphyria

• Porphyria Cutanae Tarda

• Erythropoietic Protoporphyria

Secondary

• Acquired

• lead poisining

• iron deficiency anemia

• liver disease

State the common manifestations of porphyria

• ignificant photosensitivity, where exposure to UV light triggers inflammatory reactions

  . This can also include itchy skin and hyperpigmentation

• desire to drink blood

• Port wine colored urine