100 Moderately Difficult MCQs for USMLE on Human Physiology
Based on the available evidence, I will create 100 moderately difficult multiple-choice questions covering human physiology topics including homeostasis, action potential, cell transport, and genetic control for USMLE preparation.
Homeostasis
Which of the following best describes the concept of homeostasis? A. A static state of internal equilibrium B. A dynamic process maintaining internal stability while adjusting to external changes C. The absence of feedback mechanisms D. A process requiring only negative feedback systems E. A constant internal environment regardless of external conditions
Answer: B 1
The primary purpose of homeostatic regulation is to: A. Maintain a constant body temperature B. Ensure proper cellular function through a stable internal environment C. Prevent disease D. Regulate hormone secretion E. Control neural activity
Answer: B 1
Homeostatic control systems typically include: A. Only negative feedback mechanisms B. Only positive feedback mechanisms C. Complex interactions of multiple feedback systems with hierarchical control D. Simple single-loop feedback systems E. Static regulatory mechanisms
Answer: C 1
Which statement about homeostatic regulation is FALSE? A. It involves both feedback and feedforward mechanisms B. It can adapt to changing environmental conditions C. It is a static process with fixed setpoints D. It involves multiple redundant systems E. Disruption of homeostatic mechanisms leads to disease
The concept of "milieu intérieur" that preceded our modern understanding of homeostasis was proposed by: A. Walter Cannon B. Claude Bernard C. Hippocrates D. William Harvey E. Hans Selye
Answer: B 1
Which of the following is NOT a basic controller motif in homeostatic systems? A. Inflow control B. Outflow control C. Negative feedback D. Linear control E. Integration of uptake and metabolization
Answer: D 3
In homeostatic regulation of blood glucose, insulin primarily functions as: A. An inflow controller B. An outflow controller C. Both inflow and outflow controller D. Neither inflow nor outflow controller E. A static regulator
Answer: B 3
Which of the following is an example of antagonistic hormonal control in homeostasis? A. Insulin and glucagon in glucose regulation B. Aldosterone acting alone on sodium reabsorption C. ADH acting alone on water reabsorption D. Thyroxine acting alone on metabolic rate E. Cortisol acting alone on stress response
Answer: A 3
Homeostatic dysregulation is best characterized as: A. Normal adaptation to environmental changes B. Disruption of regulatory mechanisms leading to disease C. A beneficial response to stress D. The natural aging process E. A temporary state of imbalance
Answer: B 1
The hierarchical control in homeostatic systems provides: A. Less flexibility in responding to environmental changes B. Simpler regulatory mechanisms C. Finer level of control and greater adaptability D. Fewer redundant systems E. More static setpoints
Answer: C 1
Action Potential
The action potential in cardiac cells differs from neuronal action potentials primarily due to: A. Absence of sodium channels B. Longer plateau phase due to calcium current C. Lack of potassium channels D. Absence of refractory period E. Lower threshold potential
Answer: B 4
During the depolarization phase of a neuronal action potential: A. Potassium channels open B. Sodium channels close C. Voltage-gated sodium channels open D. Chloride channels open E. Calcium channels close
Answer: C 4
The refractory period in cardiac action potentials serves to: A. Increase heart rate B. Prevent tetanic contractions C. Reduce force of contraction D. Increase calcium influx E. Enhance conduction velocity
Answer: B 4
Action potential duration restitution refers to: A. The recovery of sodium channels from inactivation B. The relationship between action potential duration and preceding diastolic interval C. The time required for complete repolarization D. The threshold potential for triggering an action potential E. The maximum rate of depolarization
Answer: B 4
Which ion channel is primarily responsible for the plateau phase (phase 2) of the cardiac action potential? A. Fast sodium channels B. L-type calcium channels C. Delayed rectifier potassium channels D. Inward rectifier potassium channels E. Chloride channels
Answer: B 4
In cardiac tissue, reentry arrhythmias emerge as a property at: A. The proteome scale B. The ion channel scale C. The cellular scale D. The tissue scale E. The organ scale
Answer: D 4
The phenomenon where action potential characteristics control the stability of reentry can be best studied using: A. Comprehensive detailed models only B. Reduced dynamic models C. Proteome analysis D. Static models E. Linear models
Answer: B 4
Which of the following is NOT a determinant of conduction velocity in cardiac tissue? A. Sodium channel availability B. Gap junction conductance C. Cell size D. Extracellular potassium concentration E. Mitochondrial function
Answer: E 4
The relationship between cardiac action potential and mechanical contraction is best described as: A. Independent processes B. Excitation-contraction coupling mediated by calcium C. Direct electrical activation of contractile proteins D. Mechanical activation triggering electrical activity E. Random association
Answer: B 4
In cardiac cells, which phase of the action potential is most vulnerable to triggered activity? A. Phase 0 (rapid depolarization) B. Phase 1 (early repolarization) C. Phase 2 (plateau) D. Phase 3 (repolarization) E. Phase 4 (resting)
Answer: D 4
Cell Transport
Which of the following transport mechanisms requires ATP hydrolysis? A. Facilitated diffusion B. Simple diffusion C. Primary active transport D. Secondary active transport E. Osmosis
Answer: C 5
The Na⁺/K⁺-ATPase pump: A. Transports 3 Na⁺ out and 2 K⁺ into the cell per ATP B. Is electrogenic, generating a net positive charge outside C. Transports 2 Na⁺ out and 3 K⁺ into the cell per ATP D. Is electroneutral E. Requires calcium for activation
Answer: A 5
Secondary active transport differs from primary active transport in that: A. It directly uses ATP B. It uses the energy stored in an ion gradient established by primary active transport C. It always moves molecules against their concentration gradient D. It is faster than primary active transport E. It requires more energy
Answer: B 5
Which of the following is NOT a characteristic that distinguishes ion channels from transporters? A. Transport rate B. Energy requirement C. Conformational changes during transport D. Molecular size E. Selectivity
Answer: D 5
The rate of transport through an ion channel compared to a carrier-mediated transporter is: A. Similar B. Much higher in channels C. Much higher in transporters D. Dependent on the ion being transported E. Independent of the concentration gradient
Answer: B 5
Adapter proteins in ion transport: A. Directly transport ions across membranes B. Provide energy for transport C. Affect subcellular localization or regulation of transport proteins D. Prevent ion transport E. Are only found in epithelial cells
Answer: C 5
The function of an ion transport protein can be modulated by: A. Only the protein's primary structure B. Only ATP availability C. Only membrane voltage D. The specific lipid composition of the local membrane microenvironment E. Only the extracellular ion concentration
Answer: D 5
Which newly identified factor is important for the fusion of transport carriers to Golgi membranes? A. TTC17 B. CCDC157 C. Clathrin D. Dynamin E. Caveolin
Answer: B 6
TTC17 knockdown affects: A. Endocytosis B. Exocytosis C. Polarized organization of Golgi cisternae and glycosylation D. Mitochondrial transport E. Nuclear transport
Answer: C 6
Which statement about ubiquitously expressed ion transport proteins is TRUE? A. They function identically in all cell types B. Their basic functional properties can vary depending on the cell type C. They are only regulated by membrane voltage D. They are not subject to post-translational modifications E. They cannot be regulated by intracellular signaling pathways
Answer: B 5
Genetic Control
Which of the following is a key challenge in understanding how genetic mutations alter protein function in cardiac disease? A. Inability to sequence ion channel genes B. Lack of computational models C. Inability to reliably extrapolate from a specific mutation to clinical presentation D. Absence of disease-producing mutations E. Lack of animal models
Answer: C 4
To understand the link between channel genotype and phenotype, which approach is most valuable? A. Clinical studies alone B. In vitro studies alone C. Systems approaches combining clinical and experimental data with computational models D. Genetic screening alone E. Pharmacological studies alone
Answer: C 4
Mathematical models of ion channels that have significant predictive abilities are based on: A. Clinical outcomes only B. Structural and functional studies of channel gating biophysics C. Gene expression patterns only D. Protein concentration only E. Cellular metabolism
Answer: B 4
Recent progress in understanding ion channel structure-function relationships has been aided by: A. Only genetic studies B. Only functional studies C. X-ray crystallography providing snapshots of gating processes D. Only computational modeling E. Only clinical observations
Answer: C 4
Which of the following is NOT a limitation in developing comprehensive human heart models? A. Limited availability of human tissues B. Lack of standardized protocols for tissue procurement C. Inadequate characterization of clinical parameters D. Abundant data on regional differences in human heart physiology E. Limited understanding of genetics in large-animal models
Answer: D 4
The study of long-QT and Brugada phenotypes has been facilitated by: A. Human tissue studies only B. Computer simulations only C. Knockout and knock-in technologies in mice D. Clinical trials only E. In vitro cell culture only
Answer: C 4
Which statement about species differences in cardiac electrophysiology is TRUE? A. Mouse and human ventricular action potentials are very similar B. Drugs that lengthen human ventricular action potentials have identical effects in all species C. Mouse and rat have especially prominent transient-outward potassium currents D. Depolarizing currents show significant species specificity E. Calcium handling is identical across all mammalian species
Answer: C 4
The development of transgenic animal models for cardiac disease has included: A. Only mice B. Mice and rats only C. Rabbits expressing long-QT syndrome or hypertrophic cardiomyopathy D. Only primates E. Only large mammals
Answer: C 4
Which technique shows promise for modifying gene expression in the hearts of large animals? A. Only viral vectors B. Only transgenic technology C. Only chemical mutagenesis D. Interfering RNA technologies E. Only homologous recombination
Answer: D 4
A major limitation of viral vectors for cardiac gene therapy is: A. Inability to target cardiac tissue B. Transient transfection and inflammatory responses leading to myocarditis C. Inability to modify ion channel function D. Excessive specificity E. Cost
Answer: B 4
Homeostasis and Ion Balance
Which statement about ion homeostasis is TRUE? A. It only involves plasma membranes B. It is maintained without energy expenditure C. It involves both plasma membranes and membranes of intracellular organelles D. It is only important for neural function E. It is independent of membrane transport proteins
Answer: C 5
The maintenance of asymmetric ion concentrations across cell membranes is: A. A minor cellular function B. Critical for most cellular functions C. Only important in excitable cells D. Independent of ATP E. Achieved solely through passive diffusion
Answer: B 5
Which of the following is NOT a major category of ion transport proteins? A. Channels B. Exchangers C. Cotransporters D. ATP-driven ion pumps E. Ionophores
Answer: E 5
In the context of homeostatic regulation, which statement is TRUE? A. Feedback redundancy decreases flexibility B. Hierarchical control results in finer level of control C. Homeostatic regulation involves only single negative feedback cycles D. Homeostasis is a static process E. Homeostasis cannot adapt to environmental changes
Answer: B 1
The concept of homeostasis was formulated by: A. Claude Bernard B. Walter Cannon C. William Harvey D. Hans Selye E. Hippocrates
Answer: B 1
Which of the following best describes the relationship between homeostasis and disease? A. Homeostasis causes disease B. Disease is independent of homeostatic mechanisms C. Disruption of homeostatic mechanisms leads to disease D. Disease always improves homeostatic function E. Homeostasis only affects healthy individuals
Answer: C 1
Effective therapy for disease should be directed toward: A. Disrupting homeostatic mechanisms B. Re-establishing homeostatic conditions C. Ignoring homeostatic mechanisms D. Preventing all feedback mechanisms E. Maintaining the disease state
Answer: B 1
Which of the following is an example of inflow control in homeostatic systems? A. Insulin lowering blood glucose B. Glucagon raising blood glucose C. Aldosterone increasing sodium reabsorption D. Sweating to reduce body temperature E. Shivering to increase body temperature
Answer: B 3
The combination of inflow and outflow controllers in cellular homeostasis allows for: A. Less precise regulation B. Integration of uptake and metabolization of controlled species C. Elimination of feedback mechanisms D. Static regulation only E. Decreased adaptability
Answer: B 3
Which statement about homeostatic controller motifs is TRUE? A. They are infinitely variable B. They can be divided into two operational work modes C. They always work independently D. They cannot be combined E. They only exist in mammals
Answer: B 3
Action Potential and Electrical Activity
In the heart, reduced (dynamic) models of electrical activity are most useful for: A. Detailed molecular analysis B. Understanding how new properties emerge from one scale to the next C. Precise prediction of drug effects D. Simulating genetic mutations E. Analyzing subcellular structures
Answer: B 4
The limitation of reduced models of cardiac action potentials is that: A. They are too complex B. They cannot represent excitability C. Phenomenologically represented parameters do not directly correspond to physical biological entities D. They cannot be used to study arrhythmias E. They require too much computational power
Answer: C 4
Comprehensive (detailed) models of cardiac electrical activity: A. Are designed to span multiple scales B. Focus only on cellular level phenomena C. Ignore structural data D. Cannot be used for clinical applications E. Are simpler than reduced models
Answer: A 4
The ideal approach to modeling cardiac electromechanical function combines: A. Only clinical observations B. Only genetic data C. Only cellular experiments D. Detailed structural data with nonlinear dynamics analysis E. Only tissue-level measurements
Answer: D 4
Which statement about simulating cardiac electromechanical function is TRUE? A. It has shown little success as an integrative approach B. It is one of the most striking examples of successful integrative multiscale modeling C. It can only be applied to animal models D. It cannot incorporate structural data E. It is limited to cellular level simulations
Answer: B 4
Modern anatomically detailed heart models integrate functions from: A. Only the cellular level B. Only the tissue level C. The ion channel/sarcomere level to whole heart electromechanical interactions D. Only genetic information E. Only protein structure
Answer: C 4
Recent extensions to cardiac electromechanical models have included: A. Only electrical mechanisms B. Only mechanical mechanisms C. Regulatory processes such as energy metabolism and signal transduction D. Only neural control E. Only hormonal regulation
Answer: C 4
A limitation of current cardiac electromechanical models is: A. They cannot represent action potentials B. They cannot simulate arrhythmias C. Model parameters are only as good as the data they fit D. They cannot incorporate ion channel kinetics E. They cannot represent tissue-level phenomena
Answer: C 4
Which of the following is a challenge in developing comprehensive human heart models? A. Excess of human tissue samples B. Too much standardization in protocols C. Limited understanding of genetics in large-animal models D. Too much information on regional differences E. Excessive computational power
Answer: C 4
The primary value of computational modeling in understanding cardiac electrophysiology is: A. Replacing experimental approaches B. Simplifying cardiac complexity C. Revealing interactions between multiple parameters simultaneously D. Eliminating the need for animal models E. Providing exact clinical predictions
Answer: C 4
Cell Transport Mechanisms
Which of the following best distinguishes ion channels from transporters? A. Molecular weight B. Location in the membrane C. Transport rate (ions/second) D. Ability to be regulated E. Presence in all cell types
Answer: C 5
The functional characterization of membrane transport proteins was a major focus of cell physiological research during: A. 1900s-1940s B. 1950s-1980s C. 1990s-2010s D. Only the 21st century E. Only before 1900
Answer: B 5
Cloning of genes encoding ion channels and transporters began in: A. The 1950s B. The 1960s C. The 1970s D. The mid-1980s E. The 2000s
Answer: D 5
Postgenomics research in ion transport biology increasingly involves: A. Only functional studies B. Only genetic studies C. Elucidation of molecular structures and exploration of cell-specific function D. Only clinical trials E. Only animal studies
Answer: C 5
The interaction of ion transport proteins with adapter proteins affects: A. Only ion selectivity B. Only transport rate C. Subcellular localization and regulation by signal transduction pathways D. Only energy requirements E. Only expression levels
Answer: C 5
The function of a ubiquitously expressed ion transport protein can vary depending on: A. Only membrane voltage B. Only extracellular ion concentrations C. Only ATP availability D. The cell type in which it is expressed E. Only temperature
Answer: D 5
Which of the following newly identified factors localizes along the secretory pathway and interacts with resident proteins of ER-Golgi membranes? A. Only TTC17 B. Only CCDC157 C. Both TTC17 and CCDC157 D. Neither TTC17 nor CCDC157 E. Only clathrin
Answer: C 6
TTC17 knockdown affects: A. Only protein synthesis B. Only protein degradation C. Polarized organization of Golgi cisternae and glycosylation D. Only endocytosis E. Only exocytosis
Answer: C 6
CCDC157 is an important factor for: A. Protein synthesis B. Protein degradation C. Fusion of transport carriers to Golgi membranes D. Nuclear transport E. Mitochondrial transport
Answer: C 6
The identification of new factors in protein transport was accomplished using: A. Traditional genetic approaches only B. Biochemical approaches only C. A pooled genome-wide CRISPRi screen D. Clinical studies only E. Electron microscopy only
Answer: C 6
Genetic Control and Regulation
Understanding how arrhythmias arise from aberrations in ion channel genes is challenging because: A. Ion channel genes cannot be sequenced B. It is not possible to reliably extrapolate from a mutation to clinical presentation C. There are no animal models available D. Ion channels do not affect cardiac rhythm E. Genetic screening is impossible
Answer: B 4
To predict altered physiological responses resulting from ion channel mutations, which approach is most effective? A. Clinical studies alone B. In vitro studies alone C. Systems approaches combining clinical and experimental data with computational models D. Genetic screening alone E. Animal studies alone
Answer: C 4
Mathematical models of ion channels with predictive abilities are based on: A. Clinical outcomes only B. Structural and functional studies of channel gating biophysics C. Gene expression patterns only D. Protein concentration only E. Cellular metabolism only
Answer: B 4
Recent progress in understanding ion channel structure-function relationships has been aided by: A. Only genetic studies B. Only functional studies C. X-ray crystallography providing snapshots of gating processes D. Only computational modeling E. Only clinical observations
Answer: C 4
The development of sufficiently detailed mathematical models of ion channels requires: A. Only clinical data B. Only genetic data C. Measurement of channel function in well-controlled reduced systems D. Only tissue-level measurements E. Only organ-level measurements
Answer: C 4
To understand the consequences of ion channel mutations on higher-order cardiac dynamics, which approach is necessary? A. Only molecular studies B. Only cellular studies C. Systems biology approaches across scales D. Only clinical observations E. Only genetic screening
Answer: C 4
Which of the following is a limitation in studying human cardiac genetics? A. Inability to sequence the human genome B. Lack of disease-producing mutations C. Inability to perform sequential functional assessments in human tissues D. Excess of human tissue samples E. Too much standardization in protocols
Answer: C 4
Mouse models are valuable for studying cardiac genetics because: A. Their action potentials are identical to humans B. They offer unique advantages for genetic manipulation C. Their calcium handling is identical to humans D. They have the same heart rate as humans E. Their ion channels are identical to humans
Answer: B 4
The study of long-QT and Brugada phenotypes has been facilitated by: A. Human tissue studies only B. Computer simulations only C. Knockout and knock-in technologies in mice D. Clinical trials only E. In vitro cell culture only
Answer: C 4
Transgenic rabbits have been developed that express: A. Only diabetes phenotypes B. Only hypertension phenotypes C. Long-QT syndrome or hypertrophic cardiomyopathy phenotypes D. Only cancer phenotypes E. Only neurological phenotypes
Answer: C 4
Integrated Physiology
The relationship between cardiac structure and function is best understood through: A. Reductionist approaches only B. Integrative approaches C. Clinical studies only D. Genetic studies only E. Biochemical studies only
Answer: B 4
Emergent properties in biological systems: A. Can always be predicted from individual components B. Are intuitive based on component knowledge C. Arise from cooperative interactions between individual components D. Only exist at the molecular level E. Are independent of scale
Answer: C 4
The statement "the whole becomes greater than the sum of the parts" in systems biology refers to: A. Mathematical errors in calculations B. Emergent properties arising from component interactions C. The physical size of biological systems D. The complexity of genetic code E. The number of molecules in a cell
Answer: B 4
Which of the following is TRUE about purely reductionist approaches to understanding biological complexity? A. They are sufficient to explain all biological phenomena B. They do not suffice to explain biological complexity C. They are more valuable than integrative approaches D. They can predict all emergent properties E. They are the only valid scientific approach
Answer: B 4
In systems biology, the greatest value of computational modeling and nonlinear dynamics lies in: A. Replacing experimental approaches B. Simplifying biological complexity C. Supporting integrative approaches to explain biological complexity D. Eliminating the need for experimental data E. Focusing only on molecular details
Answer: C 4
The advantage of computational models in studying biological systems is that: A. They eliminate the need for experiments B. A large number of parameters can be followed simultaneously C. They are always accurate D. They are simple to develop E. They can replace clinical studies
Answer: B 4
A caveat with biological modeling is that: A. It can never be accurate B. It is too simple to be useful C. The boundaries and limits of interpretation must be specified D. It can only be applied to molecular systems E. It cannot incorporate experimental data
Answer: C 4
Which statement about the action potential as an emergent property is TRUE? A. It has meaning at the proteome scale B. It emerges as a property at the scale of the cell C. It requires only a single ion channel type D. It is independent of ion channel interactions E. It can be fully understood by studying individual ion channels in isolation
Answer: B 4
Reentry as a cardiac phenomenon: A. Has meaning at the cellular scale B. Has meaning at the proteome scale C. Emerges as a property at the tissue scale D. Is independent of cellular properties E. Can be fully understood by studying single cells
Answer: C 4
Modern cardiac models have been extended beyond electrical and mechanical mechanisms to include: A. Only neural control B. Only hormonal regulation C. Regulatory processes such as energy metabolism and signal transduction D. Only genetic control E. Only developmental processes
Answer: C 4
Advanced Concepts
Which of the following is a limitation of current cardiac electromechanical models? A. They cannot represent action potentials B. They cannot simulate arrhythmias C. Mechanistic models of long-term remodeling are still in their infancy D. They cannot incorporate ion channel kinetics E. They cannot represent tissue-level phenomena
Answer: C 4
The development of comprehensive human heart models has: A. Progressed faster than animal models B. Lagged well behind those aimed at simulating animal models C. Been completed D. Been abandoned E. Focused only on genetic aspects
Answer: B 4
Strategies developed by systems biologists using simple model organisms for systematic analysis of genome-scale measurements have been: A. Extensively applied to cardiac biology B. Largely unexplored in cardiac biology C. Proven ineffective for cardiac studies D. Only useful for bacterial studies E. Only applicable to cancer research
Answer: B 4
Which of the following is NOT a challenge in implementing integrative multiscale modeling of the human heart? A. Limited availability of human tissues B. Lack of standardized protocols C. Inadequate characterization of clinical parameters D. Excess of human tissue samples E. Limited understanding of genetics in large-animal models
Answer: D 4
The workshop identified a critical need for: A. Abandoning systems approaches B. Focusing only on genetic studies C. A coordinated and integrative systems approach to understanding cardiac electromechanical activity D. Eliminating animal models E. Focusing only on clinical studies
Answer: C 4
To improve the quality and reliability of human cardiac electromechanical data, the workshop recommended: A. Abandoning human tissue studies B. Focusing only on animal models C. Supporting research on optimal conditions for human cardiac tissue procurement and handling D. Eliminating computational modeling E. Focusing only on genetic studies
Answer: C 4
The workshop recommended developing new tools and protocols for: A. Only animal studies B. Only genetic screening C. Perfusion and preservation of explanted human hearts unsuitable for transplantation D. Only computational modeling E. Only clinical trials
Answer: C 4
To improve understanding of mechanisms underlying normal and abnormal activity of the human heart, the workshop supported: A. Only clinical studies B. Only animal studies C. Basic research establishing interrelationships among kinetics and structure of human cardiac proteins D. Abandoning systems approaches E. Focusing only on genetic screening
Answer: C 4
The workshop supported comparative studies of: A. Only human cardiac gene expression B. Only animal cardiac gene expression C. Human versus animal cardiac gene expression and physiology D. Only computational models E. Only clinical outcomes
Answer: C 4
The development of large animal models modified by genetic manipulation was supported to: A. Replace human studies B. Identify mechanisms of arrhythmogenesis and heart failure development C. Eliminate the need for computational models D. Replace small animal models E. Focus only on genetic aspects
Answer: B 4