L2 Globular Protein Pathologies

Question 1

Carbon Monoxide Poisoning

Answer 1

• Leads to tissue hypoxia
• CO binds to heme much more tightly than O2
• Binding of CO to heme causes it to bind O2 with higher affinity (curve shift left)
• Hemoglobin cannot efficiently deliver O2 to tissue

Question 2

Sickle Cell Disease (HbS)

Answer 2

-Mutated B chain (point mutation, -Glu-> valine)
-Deoxy HbS (taut form) polymerizes RBCs and deforms them
-Symptoms: -anoxia/crises (from inflexible RBCs blocking capilaries)
-Hemolytic anemia -Normocytic anemia Labs: -Low RBC -Low hemoglobin -Low hematocrit -elevated reticulocyte
Gel electrophoresis: HbS

Question 3

Hemoglobin C disease (HbC)

Answer 3

-Mutated B chain (point mutation, -Glu-> +Lysine)
Symptoms: -Hemolytic anemia - Labs: -Low RBC -Low hemoglobin -Low hematocrit -elevated reticulocyte
-Gel electrophoresis: HbC

Question 4

Hemoglobin SC disease (HbSC)

Answer 4

-Mutated B chain

Symptoms: -Hemolytic anemia - Labs: -Low RBC -Low hemoglobin -Low hematocrit -elevated reticulocyte

Question 5

Methemoglobinuria

Answer 5

-Oxidation of Fe++ to Fe+++
-Fe+++ cant bind O2
-Due to excessive oxidative drugs/nitrates or hereditary mutation in NADH-cyotochrome b5 reductase (or in Hb that prevents Fe+++ reduction)
Symptoms: -chocolate colored blood -cyanosis -SOB -Headache -Seizure
Labs: -Increased Methemoglobulin -Decreased Oxyhemoglobin

Question 6

B-Thalassemias

Answer 6

-Decreased B-chain production
Symptoms: -Hemolytic anemia - -Microcytic anemia -Hypochromic anemia Labs: -Low RBC -Low hemoglobin -Low hematocrit -Increased HbF -Increased HbA2

Question 7

a-thalassemias

Answer 7

-Decreased a-chain production
Symptoms: -Hemolytic anemia-Microcytic anemia -Hypochromic anemia
Labs: -Low RBC -Low hemoglobin -Low hematocrit -Elevated reticulocyte
-HbBarts (y homotetramers) -HbH (b homotetramers) -Heinz Bodies

Question 8

Normal Adult Hb composition

Answer 8

HbA- 90%
HbF- <2%
HbA2- 2-5%
HbA1c- 3-9%