Physiology—Hemoglobin and Iron Metabolism

Lecture 3

TRUE OR FALSE: A 25-year-old pregnant woman with iron deficiency anemia would have decreased total iron binding capacity (TIBC) and increased serum ferritin levels.

False.

TRUE OR FALSE: In a patient with hereditary hemochromatosis, regular phlebotomy would decrease tissue iron deposition by upregulating hepcidin expression.

False.

TRUE OR FALSE: Unconjugated bilirubin can cross the placental barrier, which serves as a normal excretion route during fetal development since the fetal liver cannot conjugate bilirubin.

True.

TRUE OR FALSE: A patient with beta-thalassemia major receiving regular blood transfusions would have downregulated hepcidin expression, leading to increased iron absorption despite iron overload.

True.

TRUE OR FALSE: The conversion of ferric iron (Fe^{3+}) to ferrous iron (Fe^{2+}) is essential for iron absorption via DMT1 in the duodenal enterocytes.

True.

TRUE OR FALSE: Hemosiderin is water-soluble and heat-resistant up to 75\degree C, while ferritin is water-insoluble and thermally denatured.

False.

TRUE OR FALSE: In a patient with lead poisoning, the inhibition of ferrochelatase and ALA dehydratase would result in accumulation of protoporphyrin IX and delta-aminolevulinic acid.

True.

TRUE OR FALSE: During chronic inflammation, increased hepcidin expression leads to sequestration of iron in macrophages, contributing to anemia of chronic disease.

True.

TRUE OR FALSE: The daily iron requirement of 10-20 mg is fully absorbed in the duodenum, with excess iron being actively excreted through the kidneys.

False.

TRUE OR FALSE: Biliverdin reductase is found only in mammals, which explains why mammalian jaundice presents as yellow discoloration rather than green.

True.

The glycoprotein synthesized in the liver that transports iron in the ferric state through the bloodstream and represents one-third of the total iron binding capacity.

Transferrin

The chief regulator of systemic iron homeostasis that binds to ferroportin, triggering its internalization and degradation.

Hepcidin

The enzyme that catalyzes the rate-limiting step in heme synthesis, requiring succinyl-CoA, glycine, and pyridoxal phosphate as cofactors.

ALA synthase

The clinical triad consisting of cirrhosis, diabetes mellitus, and skin pigmentation seen in patients with chronic iron overload.

Bronze diabetes

The colorless compounds formed when conjugated bilirubin undergoes bacterial reduction in the terminal ileum and large intestine.

Urobilinogen

The protein complex formed when iron combines with apoferritin in mucosal cells, capable of binding 3,000-45,000 molecules of iron.

Ferritin

The specific hemoglobin variant containing four beta chains, associated with alpha-thalassemia.

Hemoglobin H (HbH)

The transporter protein responsible for transferring Fe^{2+} across the enterocyte apical membrane.

DMT1

The enzyme that opens the porphyrin ring of heme, producing biliverdin, carbon monoxide, and Fe^{2+}.

Heme oxygenase

The process by which 20-25 mg of iron is recycled daily from the destruction of 200 billion red blood cells.

Erythrophagocytosis

A 45-year-old man with chronic hepatitis C presents with elevated serum ferritin, bronze skin pigmentation, and diabetes. Which combination of laboratory findings would you expect?

a) ↓ Serum iron, ↑ TIBC, ↓ Transferrin saturation

b) ↑ Serum iron, ↑ TIBC, ↑ Transferrin saturation

c) ↑ Serum iron, ↓ TIBC, ↑ Transferrin saturation

d) ↓ Serum iron, ↓ TIBC, ↓ Transferrin saturation

c) ↑ Serum iron, ↓ TIBC, ↑ Transferrin saturation

A newborn presents with a total bilirubin of 15 mg/dL, with 14 mg/dL being unconjugated. The most likely explanation for the predominance of unconjugated bilirubin is:

a) Obstruction of the bile ducts

b) Immature hepatic conjugation enzymes

c) Increased bacterial deconjugation in the intestine

d) Defective bilirubin uptake by hepatocytes

b) Immature hepatic conjugation enzymes

In a patient with pernicious anemia (vitamin B12 deficiency), which of the following changes in iron metabolism would be expected?

a) Increased TIBC

b) Decreased TIBC

c) Increased hepcidin

d) Decreased ferritin

b) Decreased TIBC

A 6-month-old infant exclusively breastfed presents with pallor and lethargy. Laboratory tests reveal microcytic, hypochromic anemia. This presentation is most likely due to:

a) Excessive iron content in breast milk causing toxicity

b) Depletion of iron stores present at birth

c) Congenital absence of transferrin receptors

d) Upregulation of hepcidin due to frequent infections

b) Depletion of iron stores present at birth

Which of the following factors would NOT enhance iron absorption in the duodenum?

a) Ascorbic acid (Vitamin C)

b) Gastric HCl

c) Calcium supplements

d) Meat protein

c) Calcium supplements

A patient with chronic kidney disease has anemia despite iron supplementation. The mechanism most likely involves:

a) Decreased erythropoietin production leading to reduced iron utilization

b) Increased iron excretion through damaged glomeruli

c) Impaired conversion of Fe^{3+} to Fe^{2+} in the kidney

d) Competitive inhibition of iron absorption by uremic toxins

a) Decreased erythropoietin production leading to reduced iron utilization

In the synthesis of heme, which step occurs in the cytoplasm?

a) Formation of \delta-aminolevulinic acid from glycine and succinyl-CoA

b) Condensation of two ALA molecules to form porphobilinogen

c) Insertion of Fe^{2+} into protoporphyrin IX

d) Formation of coproporphyrinogen III from uroporphyrinogen III

b) Condensation of two ALA molecules to form porphobilinogen

A patient with obstructive jaundice would have which pattern of bilirubin and urobilinogen?

a) ↑ Conjugated bilirubin in serum, ↓ urobilinogen in urine

b) ↑ Unconjugated bilirubin in serum, ↑ urobilinogen in urine

c) ↑ Conjugated bilirubin in serum, ↑ urobilinogen in urine

d) ↑ Unconjugated bilirubin in serum, ↓ urobilinogen in urine

a) ↑ Conjugated bilirubin in serum, ↓ urobilinogen in urine

The oxidation of stool urobilinogen to urobilin upon exposure to air results in:

a) Lightening of stool color

b) Darkening of stool color

c) Green discoloration

d) Clay-colored stools

b) Darkening of stool color

A patient with hereditary spherocytosis presents with jaundice. The predominant type of hyperbilirubinemia would be:

a) Conjugated, due to hepatocyte dysfunction

b) Unconjugated, due to increased RBC hemolysis

c) Mixed, due to both hemolysis and bile duct obstruction

d) Conjugated, due to impaired bilirubin secretion

b) Unconjugated, due to increased RBC hemolysis

Which of the following correctly describes the relationship between transferrin and TIBC?

a) Transferrin represents the total iron binding capacity

b) Transferrin represents two-thirds of TIBC

c) Transferrin represents one-third of TIBC

d) TIBC is independent of transferrin levels

c) Transferrin represents one-third of TIBC

In a patient with acute intermittent porphyria, which enzyme deficiency in heme synthesis would lead to accumulation of porphobilinogen?

a) ALA synthase

b) ALA dehydratase

c) Porphobilinogen deaminase

d) Ferrochelatase

c) Porphobilinogen deaminase

The enterohepatic circulation of urobilinogen involves all EXCEPT:

a) Bacterial reduction of conjugated bilirubin in the intestine

b) Reabsorption of urobilinogen from the intestine

c) Re-excretion of urobilinogen by the liver

d) Complete oxidation of urobilinogen to biliverdin in hepatocytes

d) Complete oxidation of urobilinogen to biliverdin in hepatocytes

A patient with G6PD deficiency experiences hemolytic crisis after taking antimalarial drugs. The increased bilirubin production would primarily result from:

a) Impaired hepatic conjugation

b) Increased RBC destruction in the spleen

c) Decreased bacterial conversion in the gut

d) Enhanced reabsorption of urobilinogen

b) Increased RBC destruction in the spleen

The daily iron loss of 1-2 mg occurs primarily through:

a) Urinary excretion of transferrin-bound iron

b) Biliary excretion of conjugated iron

c) Desquamation of epithelial cells from skin and GIT

d) Respiratory loss through exhaled air

c) Desquamation of epithelial cells from skin and GIT

Factors that increase hepcidin expression include:

Elevated serum iron levels and chronic inflammation

Clinical features of hemochromatosis include:

Bronze diabetes, hypogonadism, hepatic cirrhosis, mental disorders

Iron is found in significant amounts in:

Hemoglobin, myoglobin, cytochrome enzymes, plasma transferrin

Conditions associated with increased serum ferritin include:

Hepatitis C infection, COVID-19, thalassemia major

The formation of \delta-aminolevulinic acid (ALA) requires:

Succinyl-CoA, glycine, and pyridoxal phosphate (vitamin B_6)

Unconjugated hyperbilirubinemia can result from:

Increased RBC hemolysis, Gilbert's syndrome, Crigler-Najjar syndrome

Functions of transferrin include:

Transport of Fe^{3+} in plasma, delivery of iron to bone marrow, regulation of iron absorption, binding to specific cell surface receptors

Lead poisoning affects heme synthesis by:

Inhibiting ALA dehydratase, inhibiting ferrochelatase, causing accumulation of ALA in urine

Normal adult hemoglobin types include:

HbA1 (\alpha2\beta2), HbA2 (\alpha2\delta2), HbF (\alpha2\gamma2)

Iron deficiency anemia can result from:

Inadequate dietary intake, chronic gastrointestinal bleeding, increased requirements during pregnancy, lead toxicity inhibiting iron incorporation

Ferritin : Iron storage :: Transferrin : ________

Iron transport

Hepcidin : Ferroportin degradation :: Erythropoietin : ________

Red blood cell production

Unconjugated bilirubin : Albumin :: Iron (Fe^{3+}) : ________

Transferrin

ALA synthase : Mitochondria :: Porphobilinogen deaminase : ________

Cytoplasm

Hemolytic jaundice : Unconjugated bilirubin :: Obstructive jaundice : ________

Conjugated bilirubin