A 33-year-old woman is brought to the emergency department 30 minutes after being rescued from a fire in her apartment. She reports nausea, headache, and dizziness. Physical examination shows black discoloration of her oral mucosa. Pulse oximetry shows an oxygen saturation of 99% on room air. The substance most likely causing symptoms in this patient primarily produces toxicity by which of the following mechanisms?

Inhibition of mitochondrial complex V

Degradation of 2,3-bisphosphoglycerate

A 24-year-old professional athlete is advised to train in the mountains to enhance his performance. After 5 months of training at an altitude of 1.5 km (5,000 feet), he is able to increase his running pace while competing at sea-level venues. Which of the following changes would produce the same effect on the oxygen-hemoglobin dissociation curve as this athlete's training did?

Decreased 2,3-bisphosphoglycerate

Increased carbon monoxide inhalation

Increased partial pressure of oxygen

A 45-year-old man is found dead in his garage. His skin appears bright cherry red, and initial toxicology screening reveals elevated carboxyhemoglobin levels. The garage door was closed, and his car's engine was running. During the autopsy, which of the following patterns of lividity would most likely be observed?

Cherry red-colored lividity concentrated in dependent areas

Yellow-colored lividity in extremities

Blue-purple lividity in dependent areas

Brown-colored lividity in non-dependent areas

A 48-year-old man is brought to the emergency department 20 minutes after being rescued from a house fire. He reports headache, metallic taste, abdominal pain, and nausea. He appears confused and agitated. His pulse is 125/min, respirations are 33/min, and blood pressure is 100/65 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 98%. Physical examination shows a bright red color of the skin. His breath smells of bitter almonds. Hyperbaric oxygen therapy and appropriate pharmacotherapy are initiated. The expected beneficial effect of this drug is most likely due to which of the following mechanisms?

Synthesis of 2,3-bisphosphoglycerate

Inhibition of cytochrome c oxidase

Dissociation of carboxyhemoglobin

An investigator is conducting a study on hematological factors that affect the affinity of hemoglobin for oxygen. An illustration of two graphs (A and B) that represent the affinity of hemoglobin for oxygen is shown. Which of the following best explains a shift from A to B?

Decreased serum 2,3-bisphosphoglycerate concentration

Increased hemoglobin γ-chain synthesis

A 30-year-old woman presents to clinic for a routine checkup. She reports that she is in good health but that she felt short of breath on her hiking and skiing trip to Colorado the week prior. She explains that this was the first time she has gone that high into the mountains and was slightly concerned for the first few days because she felt chronically short of breath. She reports a history of childhood asthma, but this experience did not feel the same. She was on the verge of seeking medical attention, but it resolved three days later, and she has felt fine ever since. What other listed physiological change results in a physiologic alteration similar to that which occurred in this patient?

Increase in concentration of 2,3-bisphosphoglycerate in blood

Increase in partial pressure of water in air

Increase in concentration of dissolved carbon dioxide in blood

Hemoglobin-oxygen binding for USMLE Step 1: High-Yield Physiology Lessons

Hemoglobin Structure - The Oxygen Taxi

Hemoglobin structure with alpha, beta chains, heme, and iron

Composition: Adult hemoglobin (HbA) is a tetramer ($α_2β_2$). Each of the four globin chains contains a heme group (iron-porphyrin) that binds one $O_2$ molecule. Total capacity: four $O_2$ per Hb.
Key Forms:
- Taut (T) form: Deoxygenated state with low $O_2$ affinity. Stabilized by ↑$H^+$, ↑$CO_2$, and ↑2,3-BPG.
- Relaxed (R) form: Oxygenated state with high $O_2$ affinity. Binding $O_2$ triggers this conformational shift.

⭐ Fetal hemoglobin (HbF, $α_2γ_2$) binds 2,3-BPG poorly, giving it a higher oxygen affinity than HbA to facilitate placental $O_2$ transfer.

Oxy-Hgb Dissociation Curve - The Great Let-Go

Sigmoid curve showing hemoglobin's (Hb) dynamic affinity for oxygen ($O_2$).
Cooperative Binding: Binding of one $O_2$ increases Hb's affinity for the next.
P50: The $PO_2$ where Hb is 50% saturated. Normal ≈ 27 mmHg. ↑P50 = ↓affinity.

Oxygen-hemoglobin dissociation curve and shifts

Right Shift: Hb "lets go" of $O_2$ to tissues.
- 📌 CADET, face Right!: ↑ CO₂, Acid, 2,3-DPG, Exercise, Temperature.
Left Shift: Hb holds on to $O_2$.
- Caused by opposite factors, plus Fetal Hb (HbF) and CO.

⭐ Fetal hemoglobin (HbF) has a low affinity for 2,3-DPG, creating a left-shifted curve. This higher $O_2$ affinity is crucial for pulling oxygen from the maternal circulation.

Curve Shifters - Right & Left Hooks

Factors that alter hemoglobin's affinity for $O_2$, shifting the dissociation curve.

Oxyhemoglobin Dissociation Curve Shifts

Right Shift (↓ $O_2$ Affinity)	Left Shift (↑ $O_2$ Affinity)
* C$O_2$ (↑)	* $CO_2$ (↓)
* Acid (↓ pH)	* Alkali (↑ pH)
* DPG (2,3-DPG) (↑)	* DPG (2,3-DPG) (↓)
* Exercise	* Temperature (↓)
* Temperature (↑)	* Fetal Hemoglobin (HbF)
📌 CADET, face Right!	* Carbon Monoxide (CO)
(for factors that shift right)	* Methemoglobin

Binding Blunders - When O2 Can't Ride

Methemoglobinemia
- Iron oxidized ($Fe^{2+} o Fe^{3+}$), can't bind $O_2$. Causes functional anemia.
- Causes: Nitrites, dapsone, anesthetics (benzocaine).
- Findings: Chocolate-colored blood, cyanosis. $SpO_2$ often reads near 85%.
- Tx: Methylene blue, Vitamin C.
Carbon Monoxide (CO) Poisoning
- CO has >200x affinity for Hb than $O_2$, ↓ $O_2$ saturation & content.
- Causes left-shift, impairing $O_2$ unloading.
- Tx: 100% $O_2$; hyperbaric $O_2$.

⭐ In CO poisoning, $PaO_2$ (dissolved $O_2$) is normal, but $SaO_2$ (Hb-bound $O_2$) is low.

High‑Yield Points - ⚡ Biggest Takeaways

Hemoglobin exhibits positive cooperativity, resulting in a sigmoidal O₂-dissociation curve.

A right shift (↓ O₂ affinity) is caused by ↑ CO₂, ↑ Acid/H⁺, ↑ 2,3-BPG, ↑ Exercise, and ↑ Temperature.

Think "CADET, face Right" for factors that promote O₂ unloading to tissues.

A left shift (↑ O₂ affinity) is caused by the opposite conditions, plus fetal hemoglobin (HbF) and CO poisoning.

Bohr effect: In tissues, ↑ H⁺ and ↑ CO₂ promote O₂ release from hemoglobin.

Haldane effect: In lungs, O₂ binding promotes the release of H⁺ and CO₂ from hemoglobin.

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