Comprehensive University Study Guide: Human Physiology and Homeostatic Mechanisms

Introduction to Physiology and Homeostatic Regulation

• Fundamental Characteristics of Living Organisms:

  • Metabolism: The sum of all chemical reactions occurring within the body.

  • Excitability: The property of living organisms that permits them to react to stimuli.

  • Reproduction: The biological process by which new individual organisms are produced.

• Homeostasis:

  • Definition: A state of reasonably stable balance between physiological variables. It is a dynamic process in which physiological variables fluctuate within a predictable range and are restored toward baseline when disturbed.

  • Importance: Homeostasis is critical because it maintains a stable internal environment necessary for normal body function. When all major organ systems operate in a homeostatic manner, a person is in good health; conversely, a loss of homeostasis may lead to disease and even life-threatening consequences.

• Regulatory Mechanisms:

  • Neural Regulation: Controls body functions through the nervous system and nerve impulses. It mainly regulates muscular and secretory activities.

  • Humoral Regulation: Controls body functions through hormones or chemical substances transported in body fluids (blood). It mainly regulates metabolic functions.

  • Autoregulation: A local control mechanism in which tissues and organs regulate their own activities locally in response to changes in their environment.

  • Function: These mechanisms maintain homeostasis by detecting changes in the internal environment and initiating corrective responses to restore normal conditions.

• Feedback and Control Systems:

  • Negative Feedback: A mechanism in which an increase or decrease in the regulated variable triggers responses that move the variable in the direction opposite to the original change, returning it toward its set point.

    • Example: Body temperature regulation. A decrease in body temperature triggers responses that increase body temperature.

  • Positive Feedback: A mechanism in which a change accelerates or amplifies a process, leading to further enhancement of the original change.

    • Example: Parturition (childbirth). Stretching of the uterus stimulates the release of oxytocin from the posterior pituitary; oxytocin causes stronger contractions, which produce more stretching and further oxytocin release until the baby is born.

  • Feedforward Regulation: An anticipatory regulatory process that activates responses before a change actually occurs, thereby reducing deviations from the set point.

  • Control Systems: The nervous system (regulating muscular/secretory activities) and the hormonal/endocrine system (regulating metabolic functions).

Cell Physiology: Membrane Transport and Signal Transduction

• Membrane Proteins:

  • Functions: Act as carriers, channels, ion pumps, receptors, and enzymes.

  • Roles: Transport substances across the membrane, receive/transmit signals, and regulate intracellular activities.

• Substance Transport Mechanisms:

  • Simple Diffusion: Movement of substances from high to low concentration without carrier proteins or energy.

  • Facilitated Diffusion: Movement down a concentration gradient using carrier or channel proteins without energy expenditure.

    • Carrier Characteristics: Specificity, saturation (maximum rate reached when all carriers are occupied), and competition (similar solutes compete for the same carrier).

  • Active Transport: Movement against a concentration gradient using metabolic energy ($ATP$). Can be primary or secondary.

  • Endocytosis: Uptake of substances into a cell via membrane-bound vesicles (includes phagocytosis and pinocytosis).

  • Exocytosis: Release of substances from a cell by fusion of vesicles with the plasma membrane.

  • Passive Transport: Movement across a membrane without cellular energy expenditure.

• Channel Gating Factors:

  • Chemical Gating: Binding of specific molecules to channel proteins.

  • Voltage Gating: Changes in membrane potential.

  • Mechanical Gating: Physical deformation or stretching of the membrane.

• Sodium-Potassium Pump ($Na^+/K^+\text{-pump}$):

  • Physiological Role: Maintains high intracellular $K^+$ and low intracellular $Na^+$ concentrations.

  • Importance: These gradients are essential for cellular electrical properties and nerve impulse transmission. It also controls cell volume by preventing excess water accumulation, swelling, and rupture.

• Signal Transduction:

  • Definition: The conversion of a chemical signal into a cellular response.

  • Main Pathways: G-protein-linked receptor pathway, ionotropic receptor pathway, and enzyme-linked receptor pathway.

Cellular Electrophysiology

• Resting Potential:

  • Definition: The resting state of a cell membrane where the inside is negative relative to the outside (Polarization).

  • Mechanism: Synaptic transmission begins when an action potential reaches the presynaptic terminal, opening voltage-gated calcium channels. $Ca^{2+}$ triggers neurotransmitter release into the synaptic cleft.

• Action Potential:

  • Definition: A rapid, temporary change in membrane potential in excitable cells.

  • Mechanism:

    1. Depolarization: Opening of voltage-gated sodium channels and influx of $Na^+$.

    2. Overshoot: The phase where the membrane potential becomes positive.

    3. Repolarization: $Na^+$ channels close and potassium channels open, allowing $K^+$ to leave the cell.

    4. Hyperpolarization: Membrane potential becomes more negative than the resting level (After-Hyperpolarization) before returning to resting potential via ion channels and the sodium-potassium pump.

  • Spike Potential: The rapid depolarization and repolarization phase.

• Local Responses (Graded Potentials):

  • Characteristics: Local, graded changes; amplitude varies with stimulus strength; decreases with distance; does not obey the all-or-none law; can summate.

  • Threshold Stimulus: The minimum strength required to trigger an action potential.

• Myelin Functions:

  • Acts as an electrical insulator, increases impulse conduction speed, enables saltatory conduction at nodes of Ranvier, and reduces energy expenditure.

Skeletal Muscle Physiology

• Excitation-Contraction Coupling:

  • Process: Action potential travels through T-tubules $\\rightarrow$ sarcoplasmic reticulum releases $Ca^{2+}$ $\\rightarrow$ $Ca^{2+}$ binds to troponin $\\rightarrow$ actin and myosin interact $\\rightarrow$ muscle contraction.

  • Relaxation: Occurs when $Ca^{2+}$ is pumped back into the sarcoplasmic reticulum.

• Cross-Bridge Cycle: The cyclic interaction between actin and myosin generating contraction within the Sarcomere (the basic structural unit between two Z lines).

• Factors Affecting Contraction: Initial muscle length, frequency of stimulation, number of motor units recruited, type of muscle fibers, and muscle fatigue.

Blood: Composition and Hemostasis

• Functions of Blood: Transport of $O_2$, $CO_2$, nutrients, hormones, and waste; maintaining homeostasis; protection (leukocytes); and prevention of blood loss (platelets/coagulation).

• Hematocrit: The percentage of blood volume occupied by erythrocytes ($45\%$ in men, $42\%$ in women).

• Osmotic Pressure:

  • Crystalloid: Produced by small substances (electrolytes); causes water movement across membranes.

  • Colloid: Generated by plasma proteins (especially albumin); draws water into blood vessels to maintain fluid distribution.

• Erythropoiesis (Red Blood Cell Production):

  • Requirements: Iron (hemoglobin synthesis), Vitamin $B_{12}$, and folic acid (DNA synthesis/maturation).

  • Regulation: Primarily by Erythropoietin (EPO) from the kidneys in response to hypoxia.

• Anemia Causes: Blood loss, decreased production (nutrient deficiencies), or increased RBC destruction (hemolytic disorders).

• Hemostasis and Coagulation:

  • Hemostasis Process: Vasoconstriction $\\rightarrow$ Platelet plug formation $\\rightarrow$ Blood coagulation $\\rightarrow$ Clot retraction $\\rightarrow$ Fibrinolysis.

  • Coagulation Steps: Prothrombin activator formation $\\rightarrow$ Prothrombin converted to Thrombin $\\rightarrow$ Fibrinogen converted to Fibrin (forming a stable meshwork).

• Anticlotting Mechanisms:

  • Protein C System: Thrombin binds thrombomodulin $\\rightarrow$ activates Protein C $\\rightarrow$ inactivates Factors Va and VIIIa.

  • Antithrombin III: Inactivates thrombin and Factors IXa, Xa, XIa, and XIIa.

  • Endothelial Cells: Smooth surface; secrete prostacyclin and nitric oxide; release tissue plasminogen activator (tPA).

  • Fibrinolysis: Plasminogen converted to Plasmin by tPA to digest fibrin and dissolve clots.

• Blood Grouping and Transfusion:

  • Cross Matching: Major (donor RBCs + recipient serum); Minor (recipient RBCs + donor serum).

  • ABO Antibodies: Naturally occurring, mostly $IgM$, do not cross placenta.

  • Rh Antibodies: Formed after exposure (transfusion/pregnancy), mostly $IgG$, can cross placenta.

  • Hemolytic Disease of the Newborn (HDN): Occurs when an $Rh^-$ mother produces antibodies against an $Rh^+$ fetus.

Cardiovascular System

• Cardiac Cycle and Dynamics:

  • Phases: Atrial systole, ventricular systole (AV valves close - $S_1$ heart sound, ejection), and ventricular diastole (semilunar valves close - $S_2$ heart sound, filling).

  • Preload: End-diastolic volume ($EDV$); determines initial stretch and force (Frank-Starling mechanism).

  • Ejection Fraction ($EF$): $EF = \frac{SV}{EDV} \times 100\%$. Normal range: $55\text{--}70\%$.

  • Pulse Pressure: $Pulse\,Pressure = Systolic\,Pressure - Diastolic\,Pressure$. Normal is approximately $40\,mmHg$.

• Cardiac Impulse: Originates in the Sinoatrial (SA) node $\\rightarrow$ AV node (delay) $\\rightarrow$ Bundle of His $\\rightarrow$ Bundle branches $\\rightarrow$ Purkinje fibers.

• Electrocardiogram (ECG):

  • P wave: Atrial depolarization.

  • PR interval: AV node conduction.

  • QRS complex: Ventricular depolarization.

  • ST segment: Complete ventricular depolarization.

  • T wave: Ventricular repolarization.

  • QT interval: Total duration of ventricular electrical activity.

• Regulation and Hemodynamics:

  • Heart Rate: Increased by sympathetic (norepinephrine) and decreased by parasympathetic (acetylcholine).

  • Peripheral Resistance: Determined by vessel diameter, blood viscosity, and vessel length.

  • Venous Return Factors: Skeletal muscle pump, respiratory pump, sympathetic venoconstriction, blood volume, right atrial pressure.

  • Edema Causes: Increased capillary hydrostatic pressure, decreased plasma colloid osmotic pressure, increased permeability, or lymphatic obstruction.

• Clinical Considerations:

  • Shock: Inadequate tissue perfusion leading to hypoxia and anaerobic metabolism.

  • Heart Block: Impaired conduction (First-degree: prolonged PR; Second-degree: dropped beats; Third-degree: complete dissociation).

Respiratory System

• Respiratory Process: Pulmonary ventilation, alveolar gas exchange, gas transport ($O_2$/$CO_2$), tissue gas exchange, and cellular respiration.

• Mechanics of Breathing:

  • Surfactant: Reduces surface tension, prevents alveolar collapse, and increases compliance.

  • Pressures: Intrapulmonary (alveolar) pressure and Intrapleural pressure (normally negative).

  • Compliance: Ease of lung expansion.

• Lung Volumes and Capacities:

  • Tidal Volume (TV): Normal breath volume.

  • Vital Capacity (VC): Max air expired after max inspiration.

  • Residual Volume (RV): Air remaining after max expiration.

  • Functional Residual Capacity (FRC): $ERV + RV$.

  • Total Lung Capacity (TLC): $VC + RV$.

• Gas exchange and Transport:

  • Diffusion Factors: Pressure gradient, surface area, membrane thickness, and diffusion coefficient.

  • Oxygen-Hb Dissociation Curve: Shifted right (facilitating unloading) by increased $PCO_2$, $H^+$ (low $pH$), temperature, and $2,3\text{-DPG}$.

• Regulation of Ventilation:

  • $CO_2$: Most important regulator; acts via central chemoreceptors.

  • $O_2$: Acts via peripheral chemoreceptors (significant when $PO_2$ drops low).

  • $H^+$: Stimulates ventilation via peripheral chemoreceptors.

Digestive System

• Secretions and Motility:

  • Saliva: Lubrication, amylase/lipase, protection (lysozyme).

  • HCl Secretion: Parietal cells use $H^+/K^+\text{-ATPase}$; $HCO_3^-$ enters blood (alkaline tide) in exchange for $Cl^-$ into the lumen.

  • Bile: Emulsification of fats and micelle formation.

  • Peristalsis: Wave-like muscle contractions propelling food.

  • Migrating Motor Complex (MMC): Fasting cyclic pattern (every $90\text{--}120\,min$) to clear the gut.

• Digestion and Absorption:

  • Carbohydrates: Amylase breaks down starch; brush border enzymes (maltase, sucrase, lactase) produce monosaccharides absorbed by active transport ($Na^+$ dependent) or facilitated diffusion.

  • Fats: Emulsification by bile $\\rightarrow$ Lipase hydrolysis $\\rightarrow$ Micelles $\\rightarrow$ Re-esterification in cells $\\rightarrow$ Chylomicrons entering lymph.

  • Vitamin $B_{12}$: Requires intrinsic factor from parietal cells; absorbed in the terminal ileum.

  • Iron: Absorbed in duodenum/jejunum; stored as ferritin.

• Regulation:

  • Secretin: Response to acid; stimulates bicarbonate release.

  • Vagus Nerve: Increases acid, motility, and gastrin.

  • Gastric Phases: Cephalic (vagal), Gastric (distension/peptides), and Intestinal (inhibitory via CCK/Secretin).

Energy Metabolism

• Metabolic Pathways:

  • Glycolysis: Cytoplasmic conversion of glucose to $2\,pyruvate$; net yield $2\,ATP$ and $2\,NADH$.

  • TCA Cycle: Mitochondrial; oxidizes Acetyl-CoA to $CO_2$; yields $12\,ATP$ per turn ($24$ per glucose).

  • Pyruvate Fate: Aerobic (Acetyl-CoA); Anaerobic (Lactate).

• Basal Metabolic Rate (BMR): Minimum energy expenditure at physical/mental rest in a postabsorptive state.

• Respiratory Quotient (RQ): Ratio of $CO_2$ produced to $O_2$ consumed (Carbs = $1.0$, Fats = $0.7$, Proteins = $0.8$).

• Hormonal Control:

  • Insulin: Anabolic; promotes storage and glucose uptake.

  • Glucagon: Catabolic; stimulates glycogenolysis and gluconeogenesis.

  • Thyroid Hormones: Increase BMR and heat generation.

Renal Physiology

• The Nephron: Consists of the renal corpuscle and renal tubule.

• Glomerular Filtration:

  • Membrane Layers: Fenestrated endothelium, basement membrane, podocytes.

  • EFP: $(\text{Capillary Hydrostatic Pressure}) - (\text{Capsule Hydrostatic Pressure}) - (\text{Capillary Colloid Osmotic Pressure}) \approx 16\,mmHg$.

  • GFR: Normal value is $125\,mL/min$ ($180\,L/day$).

• Tubular Function:

  • PCT: Reabsorbs ALL glucose/amino acids and most water/$Na^+$.

  • Renal Threshold: Concentration at which a substance starts appearing in urine (e.g., glucose).

• Regulation of Fluid Balance:

  • ADH (Vasopressin): Increases water reabsorption via Aquaporin-2 ($AQP2$) in collecting ducts. Stimulated by high osmolality (osmoreceptors) or low volume (baroreceptors).

  • RAAS: Low pressure/perfusion $\\rightarrow$ Renin $\\rightarrow$ Angiotensin I $\\rightarrow$ Angiotensin II $\\rightarrow$ Aldosterone.

  • Aldosterone: Increases $Na^+$ reabsorption and $K^+$ secretion.

Endocrine and Reproductive Systems

• Endocrine Basics:

  • Classes: Peptide/Protein, Steroid, Amine.

  • Interactions: Synergistic, Permissive, Antagonistic.

  • Growth Hormone (GH): Promotes growth, protein synthesis, and blood glucose; regulated by GHRH and Somatostatin.

  • Glucocorticoids (Cortisol): Response to stress, increases blood glucose, anti-inflammatory.

• Reproductive Physiology:

  • Spermatogenesis: Occurs in seminiferous tubules; regulated by FSH (Sertoli cells) and LH (Leydig cells/testosterone).

  • Menstrual Cycle: Follicular (estrogen/FSH), Ovulation (LH Surge mid-cycle), Luteal (progesterone).

  • Fertilization: Occurs in the ampulla; involves capacitation, acrosome reaction, and cortical reaction (prevents polyspermy).

  • Pregnancy: Placenta secretes $hCG$ (detected in pregnancy tests), progesterone, and estrogens.

  • Parturition: Initiated by oxytocin and cervical stretching (positive feedback).