NBME PHYSIOLOGY 2026 PRACTICE
EXAM QUESTIONS AND VERIFIED
ANSWERS
1
----------
Exam Section 1: Item 2 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
2. Free purine and pyrimidine bases are reutilized in normal metabolism. In children with
Lesch-Nyhan syndrome who have intellectual disability, poor muscle coordination, and
self-mutilation tendencies, there is a defect in the salvage of which of the following
pairs of bases?
A) Adenine and thymine
B) Guanine and hypoxanthine
C) Guanine and uric acid
D) Uracil and cytosine
E) Xanthine and hypoxanthine - Correct Answer B.
Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior, self-
mutilation, gout, and dystonia. The disorder is due to inactivating mutations of
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the purine
salvage
pathway, and is inherited in an X-linked recessive fashion. HGPRT catalyzes the
conversion of guanine to guanosine monophosphate and hypoxanthine to inosine
monophosphate. Patients with deficient activity of HGPRT are unable to salvage
guanine and
hypoxanthine and develop resultant increased levels of xanthine and uric acid.
Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors,
such as allopurinol or febuxostat, in order to reduce the synthesis of uric acid.
Incorrect Answers: A, C, D and E.
Adenine and thymine (Choice A) are purine and pyrimidine bases, respectively. Purine
and pyrimidine salvage are handled through two distinct pathways that are not
commonly involved in a single disease process.
Guanine and uric acid (Choice C) accumulation may occur as part of Lesch-Nyhan
syndrome, however, the accumulation of uric acid is also secondary to accumulation of
hypoxanthine. Choice B more accurately describes defective salvage of guanine and
hypoxanthine as the fundamental effect of HGPRT dysfunction. The accumulation of
uric acid is secondary.
Uracil and cytosine (Choice D) are pyrimidine nucleotides. Pyrimidine salvage is not
affected by mutations of HGPRT.
Defects of xanthine and hypoxanthine (Choice E) metabolism may result from defects in
HGPRT. However, HGPRT dysfunction results in impaired hypoxanthine salvage with
resultant excessive production of xanthine, rather than impaired xanthine salvage.
,Educational Objective: Lesch-Nyhan syndrome presents with intellectual disability,
aggressive behavior, self-mutilation, gout, and dyst
2
----------
Exam Section 1: Item 3 of 50
National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
3. A 42-year-old man is struck by a motor vehicle. His only injury is a closed fracture of
the proximal tibia. Initial neurovascular examination shows no deficits. Twenty-four
hours later, he has increased leg pain and paresthesias in the dorsal space between his
first and second toes. The patient begins to pass dark red urine and becomes oliguric.
Urinalysis is positive for blood but no erythrocytes are seen on microscopic
examination. Which of the following acute disorders is the most likely cause of the renal
failure?
A) Glomerulonephritis
B) Hemolytic-uremic syndrome
C) Interstitial nephritis
D) Nephrotic syndrome
E) Tubular necrosis - Correct Answer E.
Tibial fractures present a high risk for compartment syndrome. The fracture results in
blood vessel injury and muscle injury, inflammation, and edema. Because the fascia
containing the anterior compartment of the leg does not stretch, bleeding and swelling
can
cause increased pressure in the compartment. This increased pressure in turn inhibits
venous drainage, further increasing pressure in the compartment. Eventually the nerve
supply and associated arteries are compromised, leading to the classic signs and
symptoms of compartment syndrome. Signs and symptoms of compartment syndrome
include pain out of proportion to examination findings, pain with passive movement of
the muscles, paresthesia, pallor, pulselessness, and paralysis. Compromised blood
supply
deprives muscle and tissue of oxygen and glucose, leading to tissue ischemia and
necrosis. Muscle necrosis leads to rhabdomyolysis, myoglobinuria, and acute renal
failure. Evaluation of rhabdomyolysis reveals red or brown urine and urinalysis is
typically positive
for blood due to the presence of myoglobinuria without microscopic evidence of red
blood cells. A complication of rhabdomyolysis is acute kidney injury from acute tubular
necrosis secondary to the release of nephrotoxic myoglobin and nonprotein heme
pigments.
Acute tubular necrosis typically occurs following an ischemic or nephrotoxic insult to the
kidneys, which results in loss of the tubular epithelium. Granular, muddy brown casts
are common on urinalysis. Compartment syndrome is treated by immediate fasciotomy
to
decrease compartment pressure and support tissue perfusion.
Incorrect Answers: A, B, C, and D.
,Glomerulonephritis (Choice A) refers to a variety of glomerular diseases, including
nephritic and nephrotic syndromes. Nephritic syndromes typically present with acute
renal failure associated with h
3
----------
Exam Section 1: Item 5 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
5. A 65-year-old woman has ascites. Which of the following additional findings indicates
a diagnosis of constrictive pericarditis rather than cirrhosis?
O A) Edema of the lower extremities
B) Esophageal varices
C) Hypoalbuminemia
D) Hyponatremia
E) Increased jugular venous pressure
F) Splenomegaly - Correct Answer E.
Increased jugular venous pressure (JVP) is an expected finding in constrictive
pericarditis (CP) and would not be found in patients with volume overload secondary to
cirrhosis. CP describes a pathologic state whereby the pericardium, which encases the
entirety of
the heart and the origins of the great vessels, loses its elasticity. This can occur in
patients with viral infections, connective tissue disease, tuberculosis, or as a result of
cardiac surgery or radiation. During the normal cardiac cycle, increased venous return
to the
right atrium (RA) and right ventricle (RV) during inspiration leads to transient expansion
of the RV with slight bowing of the interventricular septum into the left ventricle (LV).
This increased RV preload does not impair LV filling as the pericardial sac expands to
accommodate the increased RV volume. In constrictive pericarditis, the pericardial sac
loses its elasticity. When venous return to the right heart increases, the pericardial sac
is unable to expand, which exacerbates movement of the interventricular septum into
the
LV. This impairs diastolic filling of the LV and reduces cardiac output. LV diastolic filling
is further reduced by a reduction in preload from the pulmonary veins. The constricted
pericardium does not respond to normal changes in intrathoracic pressure during
inspiration, but the pulmonary venous system, which lies outside of the pericardium,
experiences a normal drop in pressure during inspiration. This difference creates an
abnormal pressure gradient that reduces LV preload and leads to reduced cardiac
output. The
RV and LV develop interventricular dependence whereby increased pressure in each
ventricle begins to affect the other ventricle. CP ultimately results in equalization of
pressures in all four chambers, with clinical evidence of right heart failure exhib
4
----------
Exam Section 1: Item 4 of 50
, National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
4. A male newborn is found to have a defect in anchoring fibrils. Which of the following
skin findings is most likely in this patient?
A) Blisters
B) Easy bruising
O C) Eczematous rash
O D) Inability to sweat
O E) Thickened skin
O F) Ulcers - Correct Answer A.
The hemidesmosome is an intricate complex of proteins whose ultimate function is to
anchor the basal keratinocytes of the epidermis to the dermis at the dermal-epidermal
junction. Any impairment of the hemidesmosome will cause the basal keratinocytes to
separate from the dermis, causing a blister to form. Because the hemidesmosomes of
neighboring skin are still intact, these will be tense blisters. Anchoring fibrils are made of
type VII collagen and are a component of the hemidesmosome. A mutation or antibody
to
collagen type VII, as seen in epidermolysis bullosa, will cause blistering to occur.
Bullous pemphigoid is another disease which affects the hemidesmosome. In contrast,
pemphigus vulgaris is caused by antibodies to desmosomes, the protein complex which
maintains cell to cell adhesion in the epidermis. Because the target of pemphigus
vulgaris is more superficial, in the epidermis, those blisters will be fragile and flaccid.
Incorrect Answers: B, C, D, E, and F.
Easy bruising (Choice B) and petechiae may be seen in Vitamin C deficiency, or scurvy.
Vitamin C is necessary to produce collagen, as it is a cofactor in the hydroxylation of
proline and lysine residues, which is a key step in the conversion of preprocollagen to
procollagen.
Eczematous rashes (Choice C) may be seen in many genetic disorders including atopic
dermatitis, autosomal dominant hyper-IgE syndrome (Job syndrome), and Wiskott-
Aldrich syndrome. While acute eczematous reactions can have small vesicles due to
edema
within the epidermis, blisters are not seen. Itchy, erythematous patches are a classic
finding.
Inability to sweat (Choice D) is seen in a group of inherited disorders called ectodermal
dysplasias. In these disorders, ectoderm-derived structures including the sweat glands,
hair, teeth, and nails are abnormal. The anchoring fibrils are i
5
----------
Exam Section 1: Item 6 of 50
National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
6. A 62-year-old man is being evaluated for rectal bleeding. An x-ray of the
gastrointestinal tract with contrast material is shown. Which of the following is the most
likely explanation for the feathery appearance
EXAM QUESTIONS AND VERIFIED
ANSWERS
1
----------
Exam Section 1: Item 2 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
2. Free purine and pyrimidine bases are reutilized in normal metabolism. In children with
Lesch-Nyhan syndrome who have intellectual disability, poor muscle coordination, and
self-mutilation tendencies, there is a defect in the salvage of which of the following
pairs of bases?
A) Adenine and thymine
B) Guanine and hypoxanthine
C) Guanine and uric acid
D) Uracil and cytosine
E) Xanthine and hypoxanthine - Correct Answer B.
Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior, self-
mutilation, gout, and dystonia. The disorder is due to inactivating mutations of
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the purine
salvage
pathway, and is inherited in an X-linked recessive fashion. HGPRT catalyzes the
conversion of guanine to guanosine monophosphate and hypoxanthine to inosine
monophosphate. Patients with deficient activity of HGPRT are unable to salvage
guanine and
hypoxanthine and develop resultant increased levels of xanthine and uric acid.
Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors,
such as allopurinol or febuxostat, in order to reduce the synthesis of uric acid.
Incorrect Answers: A, C, D and E.
Adenine and thymine (Choice A) are purine and pyrimidine bases, respectively. Purine
and pyrimidine salvage are handled through two distinct pathways that are not
commonly involved in a single disease process.
Guanine and uric acid (Choice C) accumulation may occur as part of Lesch-Nyhan
syndrome, however, the accumulation of uric acid is also secondary to accumulation of
hypoxanthine. Choice B more accurately describes defective salvage of guanine and
hypoxanthine as the fundamental effect of HGPRT dysfunction. The accumulation of
uric acid is secondary.
Uracil and cytosine (Choice D) are pyrimidine nucleotides. Pyrimidine salvage is not
affected by mutations of HGPRT.
Defects of xanthine and hypoxanthine (Choice E) metabolism may result from defects in
HGPRT. However, HGPRT dysfunction results in impaired hypoxanthine salvage with
resultant excessive production of xanthine, rather than impaired xanthine salvage.
,Educational Objective: Lesch-Nyhan syndrome presents with intellectual disability,
aggressive behavior, self-mutilation, gout, and dyst
2
----------
Exam Section 1: Item 3 of 50
National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
3. A 42-year-old man is struck by a motor vehicle. His only injury is a closed fracture of
the proximal tibia. Initial neurovascular examination shows no deficits. Twenty-four
hours later, he has increased leg pain and paresthesias in the dorsal space between his
first and second toes. The patient begins to pass dark red urine and becomes oliguric.
Urinalysis is positive for blood but no erythrocytes are seen on microscopic
examination. Which of the following acute disorders is the most likely cause of the renal
failure?
A) Glomerulonephritis
B) Hemolytic-uremic syndrome
C) Interstitial nephritis
D) Nephrotic syndrome
E) Tubular necrosis - Correct Answer E.
Tibial fractures present a high risk for compartment syndrome. The fracture results in
blood vessel injury and muscle injury, inflammation, and edema. Because the fascia
containing the anterior compartment of the leg does not stretch, bleeding and swelling
can
cause increased pressure in the compartment. This increased pressure in turn inhibits
venous drainage, further increasing pressure in the compartment. Eventually the nerve
supply and associated arteries are compromised, leading to the classic signs and
symptoms of compartment syndrome. Signs and symptoms of compartment syndrome
include pain out of proportion to examination findings, pain with passive movement of
the muscles, paresthesia, pallor, pulselessness, and paralysis. Compromised blood
supply
deprives muscle and tissue of oxygen and glucose, leading to tissue ischemia and
necrosis. Muscle necrosis leads to rhabdomyolysis, myoglobinuria, and acute renal
failure. Evaluation of rhabdomyolysis reveals red or brown urine and urinalysis is
typically positive
for blood due to the presence of myoglobinuria without microscopic evidence of red
blood cells. A complication of rhabdomyolysis is acute kidney injury from acute tubular
necrosis secondary to the release of nephrotoxic myoglobin and nonprotein heme
pigments.
Acute tubular necrosis typically occurs following an ischemic or nephrotoxic insult to the
kidneys, which results in loss of the tubular epithelium. Granular, muddy brown casts
are common on urinalysis. Compartment syndrome is treated by immediate fasciotomy
to
decrease compartment pressure and support tissue perfusion.
Incorrect Answers: A, B, C, and D.
,Glomerulonephritis (Choice A) refers to a variety of glomerular diseases, including
nephritic and nephrotic syndromes. Nephritic syndromes typically present with acute
renal failure associated with h
3
----------
Exam Section 1: Item 5 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
5. A 65-year-old woman has ascites. Which of the following additional findings indicates
a diagnosis of constrictive pericarditis rather than cirrhosis?
O A) Edema of the lower extremities
B) Esophageal varices
C) Hypoalbuminemia
D) Hyponatremia
E) Increased jugular venous pressure
F) Splenomegaly - Correct Answer E.
Increased jugular venous pressure (JVP) is an expected finding in constrictive
pericarditis (CP) and would not be found in patients with volume overload secondary to
cirrhosis. CP describes a pathologic state whereby the pericardium, which encases the
entirety of
the heart and the origins of the great vessels, loses its elasticity. This can occur in
patients with viral infections, connective tissue disease, tuberculosis, or as a result of
cardiac surgery or radiation. During the normal cardiac cycle, increased venous return
to the
right atrium (RA) and right ventricle (RV) during inspiration leads to transient expansion
of the RV with slight bowing of the interventricular septum into the left ventricle (LV).
This increased RV preload does not impair LV filling as the pericardial sac expands to
accommodate the increased RV volume. In constrictive pericarditis, the pericardial sac
loses its elasticity. When venous return to the right heart increases, the pericardial sac
is unable to expand, which exacerbates movement of the interventricular septum into
the
LV. This impairs diastolic filling of the LV and reduces cardiac output. LV diastolic filling
is further reduced by a reduction in preload from the pulmonary veins. The constricted
pericardium does not respond to normal changes in intrathoracic pressure during
inspiration, but the pulmonary venous system, which lies outside of the pericardium,
experiences a normal drop in pressure during inspiration. This difference creates an
abnormal pressure gradient that reduces LV preload and leads to reduced cardiac
output. The
RV and LV develop interventricular dependence whereby increased pressure in each
ventricle begins to affect the other ventricle. CP ultimately results in equalization of
pressures in all four chambers, with clinical evidence of right heart failure exhib
4
----------
Exam Section 1: Item 4 of 50
, National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
4. A male newborn is found to have a defect in anchoring fibrils. Which of the following
skin findings is most likely in this patient?
A) Blisters
B) Easy bruising
O C) Eczematous rash
O D) Inability to sweat
O E) Thickened skin
O F) Ulcers - Correct Answer A.
The hemidesmosome is an intricate complex of proteins whose ultimate function is to
anchor the basal keratinocytes of the epidermis to the dermis at the dermal-epidermal
junction. Any impairment of the hemidesmosome will cause the basal keratinocytes to
separate from the dermis, causing a blister to form. Because the hemidesmosomes of
neighboring skin are still intact, these will be tense blisters. Anchoring fibrils are made of
type VII collagen and are a component of the hemidesmosome. A mutation or antibody
to
collagen type VII, as seen in epidermolysis bullosa, will cause blistering to occur.
Bullous pemphigoid is another disease which affects the hemidesmosome. In contrast,
pemphigus vulgaris is caused by antibodies to desmosomes, the protein complex which
maintains cell to cell adhesion in the epidermis. Because the target of pemphigus
vulgaris is more superficial, in the epidermis, those blisters will be fragile and flaccid.
Incorrect Answers: B, C, D, E, and F.
Easy bruising (Choice B) and petechiae may be seen in Vitamin C deficiency, or scurvy.
Vitamin C is necessary to produce collagen, as it is a cofactor in the hydroxylation of
proline and lysine residues, which is a key step in the conversion of preprocollagen to
procollagen.
Eczematous rashes (Choice C) may be seen in many genetic disorders including atopic
dermatitis, autosomal dominant hyper-IgE syndrome (Job syndrome), and Wiskott-
Aldrich syndrome. While acute eczematous reactions can have small vesicles due to
edema
within the epidermis, blisters are not seen. Itchy, erythematous patches are a classic
finding.
Inability to sweat (Choice D) is seen in a group of inherited disorders called ectodermal
dysplasias. In these disorders, ectoderm-derived structures including the sweat glands,
hair, teeth, and nails are abnormal. The anchoring fibrils are i
5
----------
Exam Section 1: Item 6 of 50
National Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
6. A 62-year-old man is being evaluated for rectal bleeding. An x-ray of the
gastrointestinal tract with contrast material is shown. Which of the following is the most
likely explanation for the feathery appearance
