Master Physiology
for USMLE Step 1

Core Concepts

Physiology is the study of normal function in living systems, focusing on maintaining homeostasis through complex regulatory mechanisms. USMLE Step 1 heavily tests integrated system function and regulation.

• General Principles:
  • Homeostasis: Maintenance of a stable internal environment; cornerstone of physiological function.
  • Feedback Loops:
    • Negative: Most common; opposes initial stimulus (e.g., blood glucose regulation, BP control).
    • Positive: Amplifies initial stimulus (e.g., parturition, blood clotting, action potential depolarization).
  • Compartments: Intracellular fluid (ICF) ~2/3 TBW, Extracellular fluid (ECF) ~1/3 TBW (interstitial fluid, plasma).
  • Osmolality/Tonicity: Osmolality (~285-295 mOsm/kg H2O) is total solute concentration; tonicity describes effect on cell volume (isotonic, hypotonic, hypertonic).
• Cardiovascular System:
  • Cardiac Cycle: Systole (isovolumetric contraction, ejection) and Diastole (isovolumetric relaxation, rapid filling, atrial contraction). Pressure-volume loops.
  • Cardiac Output (CO): HR x SV. SV determined by preload (EDV), afterload (SVR), contractility. Frank-Starling mechanism.
  • Blood Pressure (BP) Regulation: Baroreceptors (carotid sinus, aortic arch) for rapid control; RAAS, ADH, ANP for long-term.
  • ECG: P wave (atrial depolarization), QRS complex (ventricular depolarization), T wave (ventricular repolarization). Intervals (PR, QT) and segments (ST).
  • Microcirculation: Starling forces (hydrostatic vs. oncotic pressure) govern fluid exchange across capillaries.
• Respiratory System:
  • Ventilation: Lung volumes and capacities (Tidal, ERV, IRV, RV, VC, FRC, TLC). Compliance, airway resistance.
  • Gas Exchange: Diffusion across alveolar-capillary membrane (rate α surface area, diffusion coefficient; inversely α thickness).
  • Oxygen-Hemoglobin Dissociation Curve: Right shift (↓affinity) with ↑H+, ↑CO2, ↑temp, ↑2,3-BPG (CADET face right); left shift (↑affinity) with opposite.
  • Acid-Base Regulation: Lungs regulate CO2 (rapid); kidneys regulate HCO3- and H+ (slower).
  • V/Q Mismatch: Ventilation-perfusion ratio optimal at ~0.8. Shunt (V/Q=0) and Dead space (V/Q=∞).
• Renal System:
  • Glomerular Filtration Rate (GFR): Best indicator of kidney function. Measured by inulin or creatinine clearance. Filters ~120 mL/min.
  • Tubular Reabsorption & Secretion: Key sites and substances. Proximal Tubule (most reabsorption: Na+, water, glucose, AA); Loop of Henle (creates medullary gradient); Distal Tubule (Na+/Cl- reabsorption, K+ secretion); Collecting Duct (ADH-dependent water reabsorption, aldosterone-dependent Na+/K+ exchange).
  • Hormonal Regulation: ADH (water reabsorption), Aldosterone (Na+ reabsorption, K+ secretion), PTH (Ca++ reabsorption, PO4 excretion), ANP (Na+ excretion).
  • Acid-Base Balance: Kidneys excrete H+ and regenerate HCO3-.
• Gastrointestinal System:
  • Motility: Peristalsis, segmentation. Regulated by ENS (enteric nervous system) and ANS.
  • Secretions: Saliva (amylase, lipase), Gastric (HCl, pepsin, intrinsic factor), Pancreatic (enzymes, HCO3-), Bile (fat emulsification).
  • Absorption: Most in small intestine (carbs, proteins, fats, vitamins, minerals). Water & electrolytes in large intestine.
  • GI Hormones: Gastrin (HCl, motility), Secretin (HCO3-), CCK (pancreatic enzymes, gallbladder contraction), GIP (insulin release).
• Endocrine System:
  • Hypothalamic-Pituitary Axis: Master regulator of many endocrine glands (thyroid, adrenal cortex, gonads).
  • Hormone Classes: Peptides (water-soluble, surface receptors), Steroids (lipid-soluble, intracellular receptors), Amines.
  • Key Hormones: Insulin/Glucagon (glucose), Thyroid H. (metabolism), Cortisol (stress, glucose), Aldosterone (Na/K), PTH/Calcitonin/Vit D (Ca/PO4).
• Nervous System:
  • Action Potential: Resting potential (-70mV), depolarization (Na+ influx), repolarization (K+ efflux), hyperpolarization. All-or-none.
  • Synaptic Transmission: Neurotransmitters (ACh, NE, DA, Serotonin, GABA, Glutamate) binding to receptors. Excitation/Inhibition.
  • Autonomic Nervous System: Sympathetic (fight/flight - adrenergic receptors) vs. Parasympathetic (rest/digest - cholinergic receptors).
  • Sensory Pathways: Dorsal column-medial lemniscus (fine touch, proprioception, vibration); Spinothalamic (pain, temperature, crude touch).
  • Motor Pathways: Upper Motor Neuron (UMN) vs. Lower Motor Neuron (LMN) lesions.
• Musculoskeletal System:
  • Muscle Contraction: Sliding filament model (actin/myosin). Excitation-contraction coupling (Ca++ release from SR, troponin/tropomyosin).
  • Bone Remodeling: Osteoblasts (form bone), Osteoclasts (resorb bone). Regulated by PTH, Calcitonin, Vit D.
• Hematology & Immunology:
  • Hemostasis: Primary (platelet plug) and Secondary (coagulation cascade - intrinsic/extrinsic/common pathways).
  • Blood Typing: ABO (antigens A/B on RBCs, antibodies anti-A/B in plasma). Rh factor.

Clinical Presentation

• Physiological dysfunction often manifests as systemic symptoms. E.g., ADH dysregulation (SIADH/DI) leading to hyponatremia/hypernatremia and altered urine output.
• Cardiac output reduction (e.g., heart failure) causing fatigue, edema, dyspnea.
• Respiratory compromise (e.g., asthma, COPD) presenting as dyspnea, wheezing, altered blood gases.
• Renal failure leading to electrolyte imbalances, fluid overload, acid-base disorders.
• Endocrine imbalances causing a wide array of symptoms specific to the affected hormone (e.g., hyperthyroidism: weight loss, tachycardia, heat intolerance).
• Neurological deficits (e.g., stroke) presenting as specific motor, sensory, or cognitive impairments depending on lesion location.

Diagnosis (Gold Standard)

Assessing physiological function is key:

• Cardiovascular: ECG for electrical activity, Echocardiography for structural/functional assessment (ejection fraction), Cardiac catheterization for pressures/CO.
• Respiratory: Pulmonary Function Tests (PFTs) for lung volumes/flow rates, Arterial Blood Gases (ABGs) for gas exchange and acid-base status.
• Renal: GFR estimation (creatinine clearance, cystatin C), Serum electrolytes, Urinalysis.
• Endocrine: Basal hormone levels, dynamic stimulation/suppression tests (e.g., ACTH stimulation, glucose tolerance test).
• Neurological: Nerve Conduction Studies/EMG for peripheral nerve/muscle function, EEG for cortical electrical activity, CSF analysis for CNS environment.
• Gastrointestinal: Endoscopy for mucosal visualization, motility studies (manometry).
• Hematology: Complete Blood Count (CBC) for cell lines, Coagulation studies (PT/PTT) for clotting cascade.

Management (First Line)

Understanding physiology guides rational therapeutic interventions:

• Fluid & Electrolyte Balance: Isotonic fluids for hypovolemia, hypotonic for free water deficit, specific electrolyte replacement.
• Cardiovascular Support: Vasopressors/inotropes (sympathomimetics) for hypotension/shock, diuretics for fluid overload.
• Respiratory Support: Oxygen therapy, bronchodilators, mechanical ventilation to optimize gas exchange and mechanics.
• Hormone Replacement: For endocrine deficiencies (e.g., insulin for diabetes, thyroid hormone for hypothyroidism).
• Acid-Base Correction: Addressing the underlying cause, bicarbonate for severe metabolic acidosis, ventilation adjustments for respiratory acidosis/alkalosis.
• Renal Replacement Therapy: Dialysis to mimic GFR and maintain electrolyte/fluid balance in renal failure.

Exam Red Flags