NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
Midterm Exam: NUR631 / NUR 631
Advanced Physiology and Pathophysiology
Study Guide | Questions and Verified Answers
Latest Update
Graduate-level advanced physiology and pathophysiology with mechanism-based clinical reasoning
Total Questions Sections Options per Q Cognitive Mix
150 10 4 (A-D) 30% Recall / 50% App / 20% Analysis
This comprehensive study guide and midterm exam preparation document covers the full breadth of NUR 631
Advanced Physiology and Pathophysiology at the graduate nursing level. It spans all major physiologic systems:
cellular physiology and adaptation, genetics and epigenetics, fluid/electrolyte/acid-base balance, immune and
inflammatory mechanisms, hematology, cardiovascular, respiratory, renal, endocrine, and neurologic/musculoskeletal
physiology. Each question is mechanism-focused, requiring explanation of pathophysiologic processes rather than
symptom recall. Detailed rationales serve as study content with clinical correlations, lab value references, and study
strategy notes for midterm preparation.
Exam Structure
Section Topic Questions
Section 1: Cellular Physiology, Injury, and Adaptation - Cell Structure, Transport,
Q1-Q19 19
Homeostasis, Adaptation, Necrosis, and Apoptosis
Section 2: Genetics, Genomics, and Epigenetics - DNA, Mutations, Inheritance,
Q20-Q32 13
Gene Expression, and Genetic Testing
Section 3: Fluid, Electrolyte, and Acid-Base Physiology - Compartments,
Q33-Q49 17
Osmolality, Electrolytes, Buffers, and Compensation
Section 4: Immune and Inflammatory Physiology - Innate/Adaptive Immunity,
Q50-Q67 18
Cytokines, Hypersensitivity, Autoimmunity, and Immunodeficiency
Section 5: Hematologic Physiology and Pathophysiology - Erythropoiesis,
Q68-Q81 14
Hemoglobin, Anemias, Coagulation, and Coagulopathies
Section 6: Cardiovascular Physiology and Pathophysiology - Hemodynamics,
Q82-Q101 20
Electrophysiology, Heart Failure, Ischemia, and Atherosclerosis
Page 1
,NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
Section 7: Respiratory Physiology and Pathophysiology - Mechanics, Gas
Q102-Q117 16
Exchange, V/Q, Obstructive/Restrictive Disease, and ABG
Section 8: Renal Physiology and Pathophysiology - GFR, Tubular Function,
Q118-Q130 13
RAAS, AKI, CKD, and Acid-Base Regulation
Section 9: Endocrine Physiology and Pathophysiology - Hormone Signaling,
Q131-Q142 12
Thyroid, Adrenal, Pancreatic, and Pituitary
Section 10: Neurologic and Musculoskeletal Physiology - Neurotransmission, ICP,
Q143-Q150 8
Neuromuscular Junction, Bone, and Muscle
Section 1: Cellular Physiology, Injury, and Adaptation
Cell Structure, Transport, Homeostasis, Adaptation, Necrosis, and Apoptosis
Q1: A 58-year-old patient with chronic severe aortic stenosis develops concentric left ventricular
hypertrophy (LVH) over years. Which cellular adaptive mechanism BEST explains the increased
myocardial mass?
A. Hyperplasia — increased cell number
B. Hypertrophy — increased cell size in response to increased workload [CORRECT]
C. Metaplasia — reversible change of one cell type to another
D. Dysplasia — disordered cellular proliferation
Correct Answer: B. Hypertrophy — increased cell size in response to increased workload
Rationale: Cardiac myocytes are terminally differentiated and cannot undergo mitosis (no hyperplasia). Increased
pressure load (aortic stenosis → high afterload) induces physiological stress → increased protein synthesis → sarcomere
duplication in parallel → increased cell SIZE (hypertrophy), not number. This is concentric hypertrophy (sarcomeres
added in parallel, increased wall thickness). Volume overload (aortic regurgitation) causes eccentric hypertrophy
(sarcomeres added in series, chamber dilation). Hypertrophy is mediated by mechanosensors, GPCR signaling, mTOR
activation, and fetal gene program re-expression (ANP, BNP, β-MHC).
Q2: A long-standing cigarette smoker demonstrates squamous metaplasia of the bronchial epithelium on
biopsy. Which pathophysiologic process BEST explains this finding?
A. Reversible substitution of one mature cell type (ciliated columnar) for another (squamous) better able to
withstand the adverse environment [CORRECT]
B. Irreversible pre-neoplastic transformation with malignant potential
C. Disordered cellular proliferation with loss of polarity
D. Cellular atrophy due to chronic inflammation
Correct Answer: A. Reversible substitution of one mature cell type (ciliated columnar) for another
(squamous) better able to withstand the adverse environment
Rationale: Metaplasia is the REVERSIBLE substitution of one mature, differentiated cell type for another, usually in
response to chronic irritation — the new cell type is better able to survive the adverse environment but loses specialized
function. Ciliated pseudostratified columnar bronchial epithelium → stratified squamous (no cilia, no mucus) in smokers.
Barrett esophagus (intestinal metaplasia of distal esophagus from chronic GERD). Metaplasia itself is reversible with
irritant removal but predisposes to DYSPLASIA and malignancy via accumulated genetic changes.
Q3: A cell experiences complete ATP depletion following severe ischemia. Which metabolic consequence
occurs FIRST in the sequence of cellular injury?
A. Rupture of lysosomal membranes
Page 2
,NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
B. Failure of the Na+/K+-ATPase pump → intracellular Na+ accumulation → cellular swelling [CORRECT]
C. Activation of caspase-9
D. Nuclear chromatin clumping
Correct Answer: B. Failure of the Na+/K+-ATPase pump → intracellular Na+ accumulation → cellular
swelling
Rationale: Ischemia/reperfusion sequence of cellular injury: (1) ATP depletion (within seconds of O2 deprivation) →
failure of Na+/K+-ATPase pump → intracellular Na+ accumulation → water follows osmotically → cellular swelling
(hydropic change, reversible); (2) K+ exits cell; (3) Glycolytic shift → lactic acid accumulation → low pH → nuclear
chromatin clumping; (4) Ribosome detachment → decreased protein synthesis; (5) Membrane blebbing; (6) Mitochondrial
permeability transition pore opening → cytochrome c release → apoptosis; (7) Lysosomal membrane rupture →
irreversible injury → cell death. Caspase-9 is apoptotic (programmed).
Q4: A patient who suffers a myocardial infarction (MI) develops reperfusion injury after clot lysis.
Which pathophysiologic mechanism is the PRIMARY contributor to this paradoxical injury?
A. Resolution of intracellular acidosis
B. Generation of reactive oxygen species (ROS) — superoxide, hydrogen peroxide, hydroxyl radical — via
xanthine oxidase and mitochondrial dysfunction [CORRECT]
C. Re-establishment of ATP production
D. Reactivation of Na+/K+ pump
Correct Answer: B. Generation of reactive oxygen species (ROS) — superoxide, hydrogen peroxide, hydroxyl
radical — via xanthine oxidase and mitochondrial dysfunction
Rationale: Reperfusion injury is paradoxical worsening after blood flow restoration. Key mechanisms: (1) ROS
generation — during ischemia, ATP → hypoxanthine, xanthine dehydrogenase converted to xanthine oxidase; on
reperfusion with O2, xanthine oxidase converts hypoxanthine + O2 → xanthine + superoxide → oxidative damage to
lipids, proteins, DNA; (2) Mitochondrial dysfunction → further ROS; (3) Calcium overload (membrane Na/Ca exchanger
reverse flow, sarcoplasmic reticulum release); (4) Complement activation; (5) Neutrophil infiltration → additional ROS,
proteases; (5) Microvascular 'no-reflow'. ROS damage lipid membranes (peroxidation), protein denaturation, DNA strand
breaks. Antioxidants, Na/H exchange inhibitors, ischemic preconditioning reduce injury.
Q5: Histologic examination of a myocardial infarction 5 days post-infarction shows coagulative necrosis.
Which morphologic feature characterizes this type of necrosis?
A. Liquefaction by neutrophil enzymes producing a fluid cavity
B. Preservation of tissue architecture with cell death (ghost outlines) — protein denaturation [CORRECT]
C. Granulomatous inflammation with caseation
D. Calcium deposition in dead tissue
Correct Answer: B. Preservation of tissue architecture with cell death (ghost outlines) — protein denaturation
Rationale: Coagulative necrosis (most common) occurs in SOLID organs (heart, kidney, spleen, liver) following
ischemia. Morphology: protein denaturation (enzymatic digestion by intracellular proteases inactivated by acidosis)
preserves tissue architecture — 'ghost outlines' of cells. Eosinophilic cytoplasm, pyknotic nuclei. Gross: initially pale, then
yellow (neutrophil infiltration day 4-7), hyperemic border. Liquefactive necrosis (A) = brain infarcts, abscesses. Caseous
necrosis (C) = TB. Fat necrosis = pancreatitis. Gangrenous necrosis = ischemia + infection (dry, wet, gas).
Q6: A patient with acute pancreatitis develops enzymatic fat necrosis in peripancreatic tissue. Which
pathophysiologic mechanism is responsible?
A. Saponification of fatty acids by released lipase → calcium soap formation [CORRECT]
B. Activation of complement cascade
C. Tuberculosis infection
D. Liquefaction by neutrophil proteases
Correct Answer: A. Saponification of fatty acids by released lipase → calcium soap formation
Page 3
, NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
Rationale: Acute pancreatitis releases pancreatic enzymes (lipase, amylase) into peripancreatic tissue. Lipase digests
adipose triglycerides → free fatty acids → react with calcium → calcium soap (saponification) → chalky-white deposits;
serum calcium may decrease (clinical hypocalcemia). Histologically: shadowy outlines of adipocytes with basophilic
calcium deposits. Other necrosis types: caseous (TB) — granulomatous inflammation; liquefactive (brain, abscess);
gangrenous (limb with infection); fibrinoid (vascular — malignant HTN).
Q7: A 35-year-old patient undergoes chemotherapy targeting rapidly dividing cells. Three days after
treatment, the patient's bone marrow shows cells with fragmented nuclei (karyorrhexis), chromatin
condensation (pyknosis), and membrane blebbing. Which process is BEST responsible for these
findings?
A. Coagulative necrosis
B. Apoptosis (programmed cell death, type I) — caspase activation; characteristic morphology, no inflammation
[CORRECT]
C. Liquefactive necrosis
D. Caseous necrosis
Correct Answer: B. Apoptosis (programmed cell death, type I) — caspase activation; characteristic
morphology, no inflammation
Rationale: Apoptosis morphology: cell shrinkage, chromatin condensation (pyknosis), nuclear fragmentation
(karyorrhexis), membrane blebbing, apoptotic body formation (then phagocytosed by macrophages). NO inflammation
(no membrane rupture). Biochemical markers: cytochrome c release from mitochondria, caspase cascade (executioner
caspases 3, 6, 7), Bcl-2 family regulation, endonuclease activation (DNA ladder on gel). Triggers: (1) Intrinsic
(mitochondrial) — growth factor withdrawal, DNA damage, ER stress — regulated by Bcl-2, Bax, cytochrome c,
caspase-9; (2) Extrinsic (death receptor) — Fas/FasL, TNF/TNFR, TRAIL → caspase-8 → executioner caspases; (3)
Cytotoxic T-cell — granzyme B, perforin → caspase pathway.
Q8: A patient with familial Alzheimer disease has a mutation in the gene encoding presenilin-1. This
protein is involved in processing amyloid precursor protein (APP). This mutation leads to cellular
accumulation of misfolded proteins. Which cellular organelle is PRIMARILY affected?
A. Golgi apparatus
B. Endoplasmic reticulum (ER) — site of protein folding and quality control; misfolded proteins trigger ER
stress → unfolded protein response (UPR) [CORRECT]
C. Lysosome
D. Mitochondria
Correct Answer: B. Endoplasmic reticulum (ER) — site of protein folding and quality control; misfolded
proteins trigger ER stress → unfolded protein response (UPR)
Rationale: ER is the site of synthesis and folding of secretory/membrane proteins. ER stress (misfolded proteins, Ca
depletion, hypoxia) triggers the unfolded protein response (UPR): PERK (eIF2α → ↓ translation), ATF6 (transcription
factor for chaperones), IRE1 (XBP1 splicing → chaperones). If stress resolves, cell survives; if persistent, CHOP
activation → apoptosis. Many neurodegenerative diseases (Alzheimer, Parkinson, Huntington) and metabolic disease
(diabetes) involve ER stress. Accumulation of proteins also overwhelms ubiquitin-proteasome system → proteotoxicity.
Lysosomes (autophagy), Golgi (glycosylation) also affected.
Q9: A cell's resting membrane potential of -70 mV is maintained primarily by which mechanism?
A. Na+/K+-ATPase pump (3 Na out, 2 K in per ATP) plus selective K+ membrane permeability [CORRECT]
B. Na+/Ca2+ exchanger
C. Cl-/HCO3- exchanger
D. Glucose transporter
Correct Answer: A. Na+/K+-ATPase pump (3 Na out, 2 K in per ATP) plus selective K+ membrane
permeability
Page 4
Midterm Exam: NUR631 / NUR 631
Advanced Physiology and Pathophysiology
Study Guide | Questions and Verified Answers
Latest Update
Graduate-level advanced physiology and pathophysiology with mechanism-based clinical reasoning
Total Questions Sections Options per Q Cognitive Mix
150 10 4 (A-D) 30% Recall / 50% App / 20% Analysis
This comprehensive study guide and midterm exam preparation document covers the full breadth of NUR 631
Advanced Physiology and Pathophysiology at the graduate nursing level. It spans all major physiologic systems:
cellular physiology and adaptation, genetics and epigenetics, fluid/electrolyte/acid-base balance, immune and
inflammatory mechanisms, hematology, cardiovascular, respiratory, renal, endocrine, and neurologic/musculoskeletal
physiology. Each question is mechanism-focused, requiring explanation of pathophysiologic processes rather than
symptom recall. Detailed rationales serve as study content with clinical correlations, lab value references, and study
strategy notes for midterm preparation.
Exam Structure
Section Topic Questions
Section 1: Cellular Physiology, Injury, and Adaptation - Cell Structure, Transport,
Q1-Q19 19
Homeostasis, Adaptation, Necrosis, and Apoptosis
Section 2: Genetics, Genomics, and Epigenetics - DNA, Mutations, Inheritance,
Q20-Q32 13
Gene Expression, and Genetic Testing
Section 3: Fluid, Electrolyte, and Acid-Base Physiology - Compartments,
Q33-Q49 17
Osmolality, Electrolytes, Buffers, and Compensation
Section 4: Immune and Inflammatory Physiology - Innate/Adaptive Immunity,
Q50-Q67 18
Cytokines, Hypersensitivity, Autoimmunity, and Immunodeficiency
Section 5: Hematologic Physiology and Pathophysiology - Erythropoiesis,
Q68-Q81 14
Hemoglobin, Anemias, Coagulation, and Coagulopathies
Section 6: Cardiovascular Physiology and Pathophysiology - Hemodynamics,
Q82-Q101 20
Electrophysiology, Heart Failure, Ischemia, and Atherosclerosis
Page 1
,NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
Section 7: Respiratory Physiology and Pathophysiology - Mechanics, Gas
Q102-Q117 16
Exchange, V/Q, Obstructive/Restrictive Disease, and ABG
Section 8: Renal Physiology and Pathophysiology - GFR, Tubular Function,
Q118-Q130 13
RAAS, AKI, CKD, and Acid-Base Regulation
Section 9: Endocrine Physiology and Pathophysiology - Hormone Signaling,
Q131-Q142 12
Thyroid, Adrenal, Pancreatic, and Pituitary
Section 10: Neurologic and Musculoskeletal Physiology - Neurotransmission, ICP,
Q143-Q150 8
Neuromuscular Junction, Bone, and Muscle
Section 1: Cellular Physiology, Injury, and Adaptation
Cell Structure, Transport, Homeostasis, Adaptation, Necrosis, and Apoptosis
Q1: A 58-year-old patient with chronic severe aortic stenosis develops concentric left ventricular
hypertrophy (LVH) over years. Which cellular adaptive mechanism BEST explains the increased
myocardial mass?
A. Hyperplasia — increased cell number
B. Hypertrophy — increased cell size in response to increased workload [CORRECT]
C. Metaplasia — reversible change of one cell type to another
D. Dysplasia — disordered cellular proliferation
Correct Answer: B. Hypertrophy — increased cell size in response to increased workload
Rationale: Cardiac myocytes are terminally differentiated and cannot undergo mitosis (no hyperplasia). Increased
pressure load (aortic stenosis → high afterload) induces physiological stress → increased protein synthesis → sarcomere
duplication in parallel → increased cell SIZE (hypertrophy), not number. This is concentric hypertrophy (sarcomeres
added in parallel, increased wall thickness). Volume overload (aortic regurgitation) causes eccentric hypertrophy
(sarcomeres added in series, chamber dilation). Hypertrophy is mediated by mechanosensors, GPCR signaling, mTOR
activation, and fetal gene program re-expression (ANP, BNP, β-MHC).
Q2: A long-standing cigarette smoker demonstrates squamous metaplasia of the bronchial epithelium on
biopsy. Which pathophysiologic process BEST explains this finding?
A. Reversible substitution of one mature cell type (ciliated columnar) for another (squamous) better able to
withstand the adverse environment [CORRECT]
B. Irreversible pre-neoplastic transformation with malignant potential
C. Disordered cellular proliferation with loss of polarity
D. Cellular atrophy due to chronic inflammation
Correct Answer: A. Reversible substitution of one mature cell type (ciliated columnar) for another
(squamous) better able to withstand the adverse environment
Rationale: Metaplasia is the REVERSIBLE substitution of one mature, differentiated cell type for another, usually in
response to chronic irritation — the new cell type is better able to survive the adverse environment but loses specialized
function. Ciliated pseudostratified columnar bronchial epithelium → stratified squamous (no cilia, no mucus) in smokers.
Barrett esophagus (intestinal metaplasia of distal esophagus from chronic GERD). Metaplasia itself is reversible with
irritant removal but predisposes to DYSPLASIA and malignancy via accumulated genetic changes.
Q3: A cell experiences complete ATP depletion following severe ischemia. Which metabolic consequence
occurs FIRST in the sequence of cellular injury?
A. Rupture of lysosomal membranes
Page 2
,NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
B. Failure of the Na+/K+-ATPase pump → intracellular Na+ accumulation → cellular swelling [CORRECT]
C. Activation of caspase-9
D. Nuclear chromatin clumping
Correct Answer: B. Failure of the Na+/K+-ATPase pump → intracellular Na+ accumulation → cellular
swelling
Rationale: Ischemia/reperfusion sequence of cellular injury: (1) ATP depletion (within seconds of O2 deprivation) →
failure of Na+/K+-ATPase pump → intracellular Na+ accumulation → water follows osmotically → cellular swelling
(hydropic change, reversible); (2) K+ exits cell; (3) Glycolytic shift → lactic acid accumulation → low pH → nuclear
chromatin clumping; (4) Ribosome detachment → decreased protein synthesis; (5) Membrane blebbing; (6) Mitochondrial
permeability transition pore opening → cytochrome c release → apoptosis; (7) Lysosomal membrane rupture →
irreversible injury → cell death. Caspase-9 is apoptotic (programmed).
Q4: A patient who suffers a myocardial infarction (MI) develops reperfusion injury after clot lysis.
Which pathophysiologic mechanism is the PRIMARY contributor to this paradoxical injury?
A. Resolution of intracellular acidosis
B. Generation of reactive oxygen species (ROS) — superoxide, hydrogen peroxide, hydroxyl radical — via
xanthine oxidase and mitochondrial dysfunction [CORRECT]
C. Re-establishment of ATP production
D. Reactivation of Na+/K+ pump
Correct Answer: B. Generation of reactive oxygen species (ROS) — superoxide, hydrogen peroxide, hydroxyl
radical — via xanthine oxidase and mitochondrial dysfunction
Rationale: Reperfusion injury is paradoxical worsening after blood flow restoration. Key mechanisms: (1) ROS
generation — during ischemia, ATP → hypoxanthine, xanthine dehydrogenase converted to xanthine oxidase; on
reperfusion with O2, xanthine oxidase converts hypoxanthine + O2 → xanthine + superoxide → oxidative damage to
lipids, proteins, DNA; (2) Mitochondrial dysfunction → further ROS; (3) Calcium overload (membrane Na/Ca exchanger
reverse flow, sarcoplasmic reticulum release); (4) Complement activation; (5) Neutrophil infiltration → additional ROS,
proteases; (5) Microvascular 'no-reflow'. ROS damage lipid membranes (peroxidation), protein denaturation, DNA strand
breaks. Antioxidants, Na/H exchange inhibitors, ischemic preconditioning reduce injury.
Q5: Histologic examination of a myocardial infarction 5 days post-infarction shows coagulative necrosis.
Which morphologic feature characterizes this type of necrosis?
A. Liquefaction by neutrophil enzymes producing a fluid cavity
B. Preservation of tissue architecture with cell death (ghost outlines) — protein denaturation [CORRECT]
C. Granulomatous inflammation with caseation
D. Calcium deposition in dead tissue
Correct Answer: B. Preservation of tissue architecture with cell death (ghost outlines) — protein denaturation
Rationale: Coagulative necrosis (most common) occurs in SOLID organs (heart, kidney, spleen, liver) following
ischemia. Morphology: protein denaturation (enzymatic digestion by intracellular proteases inactivated by acidosis)
preserves tissue architecture — 'ghost outlines' of cells. Eosinophilic cytoplasm, pyknotic nuclei. Gross: initially pale, then
yellow (neutrophil infiltration day 4-7), hyperemic border. Liquefactive necrosis (A) = brain infarcts, abscesses. Caseous
necrosis (C) = TB. Fat necrosis = pancreatitis. Gangrenous necrosis = ischemia + infection (dry, wet, gas).
Q6: A patient with acute pancreatitis develops enzymatic fat necrosis in peripancreatic tissue. Which
pathophysiologic mechanism is responsible?
A. Saponification of fatty acids by released lipase → calcium soap formation [CORRECT]
B. Activation of complement cascade
C. Tuberculosis infection
D. Liquefaction by neutrophil proteases
Correct Answer: A. Saponification of fatty acids by released lipase → calcium soap formation
Page 3
, NUR 631 Advanced Physiology and Pathophysiology Midterm - Complete Questions & Answers
Rationale: Acute pancreatitis releases pancreatic enzymes (lipase, amylase) into peripancreatic tissue. Lipase digests
adipose triglycerides → free fatty acids → react with calcium → calcium soap (saponification) → chalky-white deposits;
serum calcium may decrease (clinical hypocalcemia). Histologically: shadowy outlines of adipocytes with basophilic
calcium deposits. Other necrosis types: caseous (TB) — granulomatous inflammation; liquefactive (brain, abscess);
gangrenous (limb with infection); fibrinoid (vascular — malignant HTN).
Q7: A 35-year-old patient undergoes chemotherapy targeting rapidly dividing cells. Three days after
treatment, the patient's bone marrow shows cells with fragmented nuclei (karyorrhexis), chromatin
condensation (pyknosis), and membrane blebbing. Which process is BEST responsible for these
findings?
A. Coagulative necrosis
B. Apoptosis (programmed cell death, type I) — caspase activation; characteristic morphology, no inflammation
[CORRECT]
C. Liquefactive necrosis
D. Caseous necrosis
Correct Answer: B. Apoptosis (programmed cell death, type I) — caspase activation; characteristic
morphology, no inflammation
Rationale: Apoptosis morphology: cell shrinkage, chromatin condensation (pyknosis), nuclear fragmentation
(karyorrhexis), membrane blebbing, apoptotic body formation (then phagocytosed by macrophages). NO inflammation
(no membrane rupture). Biochemical markers: cytochrome c release from mitochondria, caspase cascade (executioner
caspases 3, 6, 7), Bcl-2 family regulation, endonuclease activation (DNA ladder on gel). Triggers: (1) Intrinsic
(mitochondrial) — growth factor withdrawal, DNA damage, ER stress — regulated by Bcl-2, Bax, cytochrome c,
caspase-9; (2) Extrinsic (death receptor) — Fas/FasL, TNF/TNFR, TRAIL → caspase-8 → executioner caspases; (3)
Cytotoxic T-cell — granzyme B, perforin → caspase pathway.
Q8: A patient with familial Alzheimer disease has a mutation in the gene encoding presenilin-1. This
protein is involved in processing amyloid precursor protein (APP). This mutation leads to cellular
accumulation of misfolded proteins. Which cellular organelle is PRIMARILY affected?
A. Golgi apparatus
B. Endoplasmic reticulum (ER) — site of protein folding and quality control; misfolded proteins trigger ER
stress → unfolded protein response (UPR) [CORRECT]
C. Lysosome
D. Mitochondria
Correct Answer: B. Endoplasmic reticulum (ER) — site of protein folding and quality control; misfolded
proteins trigger ER stress → unfolded protein response (UPR)
Rationale: ER is the site of synthesis and folding of secretory/membrane proteins. ER stress (misfolded proteins, Ca
depletion, hypoxia) triggers the unfolded protein response (UPR): PERK (eIF2α → ↓ translation), ATF6 (transcription
factor for chaperones), IRE1 (XBP1 splicing → chaperones). If stress resolves, cell survives; if persistent, CHOP
activation → apoptosis. Many neurodegenerative diseases (Alzheimer, Parkinson, Huntington) and metabolic disease
(diabetes) involve ER stress. Accumulation of proteins also overwhelms ubiquitin-proteasome system → proteotoxicity.
Lysosomes (autophagy), Golgi (glycosylation) also affected.
Q9: A cell's resting membrane potential of -70 mV is maintained primarily by which mechanism?
A. Na+/K+-ATPase pump (3 Na out, 2 K in per ATP) plus selective K+ membrane permeability [CORRECT]
B. Na+/Ca2+ exchanger
C. Cl-/HCO3- exchanger
D. Glucose transporter
Correct Answer: A. Na+/K+-ATPase pump (3 Na out, 2 K in per ATP) plus selective K+ membrane
permeability
Page 4
