NBME PHYSIOLOGY 2026 UPDATED
COMPREHENSIVE EXAM QUESTIONS & VERIFIED
ANSWERS GRADED A+ BUNDLE
This high-yield question bank features USMLE-style multiple-choice
questions with italicized answers and detailed, bolded rationales
covering all major organ systems. It mirrors the updated 2026 NBME
Physiology content breakdown to thoroughly test cell physiology,
cardiovascular dynamics, renal function, and neurobiology. It serves as
an optimized, comprehensive self-assessment resource perfect for
medical students aiming for top-tier marks on their board preparation
and shelf exams.
Cell & General Physiology (Questions 1–10)
1. A 24-year-old medical student is researching cell
membrane transport mechanisms. She notes that a
specific substance crosses the alveolar-capillary
membrane rapidly along its electrochemical gradient
without requiring a carrier protein or cellular energy.
Which of the following transport mechanisms is being
described?
A) Primary active transport
B) Secondary active transport
C) Facilitated diffusion
D) Simple diffusion
Answer: D
, Rationale: Simple diffusion describes the
unassisted movement of lipid-soluble substances
(like O₂ and CO₂) directly through the lipid bilayer
down their concentration gradient. It requires no
carrier proteins or ATP.
2. An experimental drug blocks the function of the
Na⁺/K⁺-ATPase pump in skeletal muscle cells. Which
of the following intracellular electrolyte changes will
most likely occur?
A) Increased sodium, increased potassium
B) Decreased sodium, decreased potassium
C) Increased sodium, decreased potassium
D) Decreased sodium, increased potassium
Answer: C
Rationale: The Na⁺/K⁺-ATPase pump normally
pumps 3 Na⁺ ions out of the cell and 2 K⁺ ions
into the cell. Inhibiting this active pump stops this
process, causing intracellular Na⁺ to accumulate
and intracellular K⁺ to leak out and deplete.
3. A researcher exposes isolated nerve fibers to a toxin
that selectively blocks voltage-gated sodium
channels. Which phase of the action potential will be
completely abolished?
, A) Depolarization
B) Repolarization
C) Hyperpolarization
D) Resting membrane potential
Answer: A
Rationale: The upstroke or depolarization phase
of an action potential is mediated by the rapid
influx of Na⁺ ions into the cell through voltage-
gated Na⁺ channels. Blocking these channels
prevents depolarization from occurring.
4. During an experiment, the extracellular potassium
concentration surrounding a giant squid axon is
significantly increased. What is the immediate effect
on the resting membrane potential of the nerve cell?
A) It becomes more negative (hyperpolarizes)
B) It becomes less negative (depolarizes)
C) It remains entirely unchanged
D) It fluctuates unpredictably
Answer: B
Rationale: The resting membrane potential is
highly dependent on the chemical gradient of K⁺.
Increasing extracellular K⁺ decreases the
concentration gradient, reducing the efflux of K⁺
, out of the cell through leak channels, making the
interior less negative (depolarized).
5. A 32-year-old man presents with severe fatigue and
muscle weakness. Muscle biopsy confirms a defect in
a cell surface receptor that links an extracellular
ligand to an intracellular G-protein, activating
phospholipase C. Which of the following secondary
messengers will increase as a direct result of this
pathway?
A) Cyclic AMP (cAMP)
B) Cyclic GMP (cGMP)
C) Inositol 1,4,5-trisphosphate (IP₃)
D) Nitric Oxide (NO)
Answer: C
Rationale: The \(G_{q}\) protein pathway activates
phospholipase C, which cleaves membrane-
bound PIP₂ into two key secondary messengers:
inositol 1,4,5-trisphosphate (IP₃) and
diacylglycerol (DAG).
6. A molecular biologist isolates a substance that moves
glucose into skeletal muscle cells against its
concentration gradient by utilizing the downward
concentration gradient of sodium ions. What type of
COMPREHENSIVE EXAM QUESTIONS & VERIFIED
ANSWERS GRADED A+ BUNDLE
This high-yield question bank features USMLE-style multiple-choice
questions with italicized answers and detailed, bolded rationales
covering all major organ systems. It mirrors the updated 2026 NBME
Physiology content breakdown to thoroughly test cell physiology,
cardiovascular dynamics, renal function, and neurobiology. It serves as
an optimized, comprehensive self-assessment resource perfect for
medical students aiming for top-tier marks on their board preparation
and shelf exams.
Cell & General Physiology (Questions 1–10)
1. A 24-year-old medical student is researching cell
membrane transport mechanisms. She notes that a
specific substance crosses the alveolar-capillary
membrane rapidly along its electrochemical gradient
without requiring a carrier protein or cellular energy.
Which of the following transport mechanisms is being
described?
A) Primary active transport
B) Secondary active transport
C) Facilitated diffusion
D) Simple diffusion
Answer: D
, Rationale: Simple diffusion describes the
unassisted movement of lipid-soluble substances
(like O₂ and CO₂) directly through the lipid bilayer
down their concentration gradient. It requires no
carrier proteins or ATP.
2. An experimental drug blocks the function of the
Na⁺/K⁺-ATPase pump in skeletal muscle cells. Which
of the following intracellular electrolyte changes will
most likely occur?
A) Increased sodium, increased potassium
B) Decreased sodium, decreased potassium
C) Increased sodium, decreased potassium
D) Decreased sodium, increased potassium
Answer: C
Rationale: The Na⁺/K⁺-ATPase pump normally
pumps 3 Na⁺ ions out of the cell and 2 K⁺ ions
into the cell. Inhibiting this active pump stops this
process, causing intracellular Na⁺ to accumulate
and intracellular K⁺ to leak out and deplete.
3. A researcher exposes isolated nerve fibers to a toxin
that selectively blocks voltage-gated sodium
channels. Which phase of the action potential will be
completely abolished?
, A) Depolarization
B) Repolarization
C) Hyperpolarization
D) Resting membrane potential
Answer: A
Rationale: The upstroke or depolarization phase
of an action potential is mediated by the rapid
influx of Na⁺ ions into the cell through voltage-
gated Na⁺ channels. Blocking these channels
prevents depolarization from occurring.
4. During an experiment, the extracellular potassium
concentration surrounding a giant squid axon is
significantly increased. What is the immediate effect
on the resting membrane potential of the nerve cell?
A) It becomes more negative (hyperpolarizes)
B) It becomes less negative (depolarizes)
C) It remains entirely unchanged
D) It fluctuates unpredictably
Answer: B
Rationale: The resting membrane potential is
highly dependent on the chemical gradient of K⁺.
Increasing extracellular K⁺ decreases the
concentration gradient, reducing the efflux of K⁺
, out of the cell through leak channels, making the
interior less negative (depolarized).
5. A 32-year-old man presents with severe fatigue and
muscle weakness. Muscle biopsy confirms a defect in
a cell surface receptor that links an extracellular
ligand to an intracellular G-protein, activating
phospholipase C. Which of the following secondary
messengers will increase as a direct result of this
pathway?
A) Cyclic AMP (cAMP)
B) Cyclic GMP (cGMP)
C) Inositol 1,4,5-trisphosphate (IP₃)
D) Nitric Oxide (NO)
Answer: C
Rationale: The \(G_{q}\) protein pathway activates
phospholipase C, which cleaves membrane-
bound PIP₂ into two key secondary messengers:
inositol 1,4,5-trisphosphate (IP₃) and
diacylglycerol (DAG).
6. A molecular biologist isolates a substance that moves
glucose into skeletal muscle cells against its
concentration gradient by utilizing the downward
concentration gradient of sodium ions. What type of
