General Physiology: The Foundation of Life and Cellular Function.pptx

Every living system begins with one fundamental unit — the cell. This presentation takes you on a clear, concept-driven journey through General Physiology, explaining how the human body maintains balance and function from the cellular level to the system level.

Here’s what you’ll explore inside:
🔹 The structure and function of cells and organelles
🔹 Cell membrane dynamics and transport mechanisms
🔹 Homeostasis and feedback control systems
🔹 Acid–base balance and physiological regulation
🔹 Clinical correlations to understand “why things go wrong”
🔹 Simplified visuals and examples for better learning and retention

1. General Physiology PREPARED BY Dr. SOMA BALAJI PT MSK & SPORTS

2. Cell – The Structural and Functional Unit of Life

3. General Characteristics of a Cell Each cell in the human body: Requires nutrition and oxygen for energy. Produces energy for growth, repair, and cellular activities. Eliminates carbon dioxide and other metabolic wastes. Maintains internal environment essential for its survival. Responds immediately to external stimuli or invasion (toxins, bacteria). Reproduces by division (except neurons).

4. Organization of Living Matter Tissue: Group of cells with similar function and structure. Four primary types: Muscle tissue Nervous tissue Epithelial tissue Connective tissue Organ: Structure made up of two or more primary tissues performing a specific function (e.g., heart, liver, kidney). System: A group of organs working together for a common function (e.g., cardiovascular, digestive, nervous systems).

5. Structural Overview of the Cell A typical human cell consists of: Cell membrane (Plasma membrane / Plasmalemma) Cytoplasm (with organelles) Nucleus

6. Cell Membrane The cell membrane is a protective semipermeable sheath enclosing the cell body. Separates: Extracellular Fluid (ECF) – outside Intracellular Fluid (ICF) – inside Thickness: 75–111 Å Other names: Plasma membrane or Plasmalemma.

7. Composition of Cell Membrane

8. Structural Models of the Cell Membrane Danielli–Davson Model (1935): Lipid layer “sandwiched” between two protein layers. Early concept of membrane organization.

9. 2. Unit Membrane Model (Robertson, 1957): Three layers: central lipid + two protein layers.

10. 3. Fluid Mosaic Model (Singer & Nicolson, 1972): Modern accepted model. Lipid bilayer with floating proteins forming a “mosaic.” Proteins move within the lipid matrix → fluid nature.

11. Lipid Layer of Cell Membrane Lipid bilayer: Two layers of phospholipid molecules. Each molecule has: Head (Hydrophilic): water-loving, polar end. Tail (Hydrophobic): water-repelling, nonpolar end. Arrangement: Tails face inward (avoid water). Heads face outward (toward ECF and ICF). Function: Allows passage of fat-soluble substances (O₂, CO₂, alcohol). Restricts water-soluble molecules (glucose, ions).

12. Phospholipids and Cholesterol Phospholipids: Major lipid component (e.g., phosphatidylcholine, sphingomyelin). Cholesterol: Interspersed between phospholipids. Provides stability and rigidity. Reduces membrane permeability. Maintains fluid consistency.

13. Proteins of Cell Membrane Types: I ntegral (Transmembrane) Proteins: Span the entire membrane thickness. Functions: Channels, carriers, pumps, receptors, enzymes, antigens, adhesion molecules. 2. Peripheral Proteins: Loosely attached to membrane surface (internal/external). Functions: Structural support, enzymatic reactions, cytoskeletal anchoring.

14. Functions of Membrane Proteins Provide structural stability. Act as enzymes in metabolic reactions. Function as receptors for hormones & neurotransmitters. Serve as channels and carriers for transport. Act as antigens for immune recognition. Form cell adhesion molecules (CAMs) for tissue integrity.

15. Carbohydrates of Cell Membrane Found as glycoproteins or glycolipids. Form a loose, thin covering called Glycocalyx. Functions: Impart negative charge → repel other negative substances. Involved in cell recognition (immune defense). Act as receptor sites for hormones. Facilitate adhesion between neighboring cells.

16. Functions of Cell Membrane Protective: Covers and shields cellular contents. Selective permeability: Controls entry and exit. Absorptive: Allows nutrient uptake. Excretory: Eliminates waste and metabolites. Exchange of gases: O₂ and CO₂ diffusion. Maintenance of cell shape and size.

17. Cytoplasm Cytoplasm: Jelly-like medium (80% water) surrounding nucleus. Contains cytosol and various organelles. Divided into: Ectoplasm: Outer layer beneath membrane. Endoplasm: Inner region around nucleus.

18. Cytoplasmic Organelles – Classification

19. Endoplasmic Reticulum (ER) – Structure Network of interconnected tubular and vesicular structures. Limiting membrane: protein + lipid bilayer. Lumen: Contains fluid medium (endoplasmic matrix). Connection: Between nuclear membrane and cell membrane. Types: Rough (Granular) ER: Has ribosomes. Smooth (Agranular) ER: No ribosomes.

20. Rough Endoplasmic Reticulum (RER) Structure: Ribosome-studded outer surface → rough appearance. Functions: Protein synthesis: Forms structural & secretory proteins (e.g., insulin, antibodies). Glycosylation: Adds carbohydrate chains to proteins → glycoproteins. Transport: Sends vesicles to Golgi apparatus. Degradation of worn-out organelles (forms autophagosomes for lysosomal digestion).

21. Smooth Endoplasmic Reticulum (SER) Structure: Interconnected tubular network, smooth surface. Functions: Synthesis of lipids & steroids (e.g., cholesterol, phospholipids, steroid hormones). Detoxification of drugs & toxins (especially in liver). Storage and metabolism of Ca²⁺ (in muscle – sarcoplasmic reticulum). Carbohydrate metabolism and cellular detoxification.

22. Golgi Apparatus Structure: Flattened membranous sacs (cisternae), located near nucleus. Cis face: Receives materials from ER. Trans face: Dispatches processed materials. Functions: Processing & modification of proteins and lipids. Packaging into secretory vesicles and lysosomes. Labeling & sorting for specific destinations. Called the “Post office” or “Shipping department” of the cell.

23. Lysosomes Membrane-bound vesicles containing hydrolytic enzymes. Formed by Golgi apparatus. Two types: Primary (inactive) Secondary (active; fused with endosomes or phagosomes) Functions: Heterophagy: Digestion of engulfed material. Autophagy: Removal of worn-out organelles. Degradation of macromolecules. Secretory function: Secrete perforin, granzymes, melanin, serotonin. Known as “Suicidal bags” or “Garbage disposal units.”

24. Peroxisomes Structure: Small, membrane-bound spherical organelles. Contain oxidative enzymes like catalase, urate oxidase, D-amino acid oxidase. Functions: Oxidation of long-chain fatty acids → acetyl-CoA. Detoxification of hydrogen peroxide (H₂O₂ → H₂O + O₂ by catalase). Synthesis of plasmalogens – essential for myelin sheath formation. Role in lipid metabolism and cellular detoxification (especially in liver, kidney). Clinical Note: Peroxisomal disorders → Zellweger syndrome, Adrenoleukodystrophy (ALD).

25. Mitochondria Powerhouse of the cell. Present in all cells except RBCs. Number per cell: 100–5000 depending on energy need. Shape: Spherical or filamentous. Size: 0.5–1 µm wide, 1–10 µm long. Membranes: Double – outer smooth, inner folded into cristae. Matrix: Contains enzymes, DNA, RNA, and ribosomes.

26. Functions of Mitochondria ATP Production (Oxidative Phosphorylation): Food → breakdown → CO₂ + H₂O + Energy (ATP). Major site for Electron Transport Chain (ETC) and ATP synthase. Regulation of Cellular Metabolism: Citric Acid (Krebs) Cycle enzymes are mitochondrial. Apoptosis Initiation: Release of cytochrome c activates cell death pathways. Heat Production (Thermogenesis): Especially in brown fat cells (non-shivering thermogenesis). Calcium storage and signaling. Clinical Note: Mitochondrial myopathies (e.g., Kearns-Sayre syndrome, Leber’s optic neuropathy).

27. Ribosomes Structure: Non-membranous, dense granules made of rRNA + proteins. Two subunits: Large (60S) and Small (40S) → together form 80S (in eukaryotes). Found: Free in cytoplasm (→ cytoplasmic proteins). Attached to RER (→ secretory proteins). Functions: Protein synthesis: mRNA attaches → tRNA brings amino acids → peptide chain formed. Polyribosomes: Multiple ribosomes translating one mRNA simultaneously.

28. Centrosome and Centrioles Structure: Located near nucleus. Contains two centrioles perpendicular to each other, surrounded by pericentriolar material. Each centriole → 9 triplets of microtubules (9×3). Functions: Formation of spindle fibers during mitosis/meiosis. Formation of basal bodies → cilia & flagella. Organization of microtubules within the cytoskeleton.

29. Cytoskeleton Definition: A dynamic network of filamentous proteins providing internal framework, shape, and movement. Components: Microfilaments (actin & myosin) Intermediate filaments (keratin, vimentin) Microtubules (tubulin)

30. Functions of Cytoskeleton Maintains cell shape and mechanical support. Anchors organelles in place. Enables intracellular transport (via motor proteins kinesin & dynein). Forms cilia, flagella, and mitotic spindle. Facilitates cell movement and contraction. Provides structural link between cell membrane and nucleus.

31. Cilia and Flagella Cilia: Numerous short projections (e.g., respiratory epithelium). Flagella: Single long projection (e.g., sperm tail). Structure:9+2 microtubule arrangement. Functions: Cilia: Move mucus or fluids over epithelial surfaces. Flagella: Propulsion of cell. Clinical Note: Kartagener’s syndrome – ciliary dyskinesia causing infertility and respiratory issues.

32. Nucleus Definition: The control center of the cell containing genetic material responsible for heredity and cellular functions. Present in all cells except RBCs and platelets. Shape: Usually spherical. Number: Generally one per cell; multinucleated in skeletal muscle; absent in mature RBCs.

33. Structure of Nucleus Nuclear envelope: Double membrane with nuclear pores. Nucleoplasm: Semi-fluid matrix containing chromatin and nucleolus. Chromatin: DNA + histone proteins. Nucleolus: Dense body for rRNA synthesis.

34. Nuclear Membrane Outer membrane: Continuous with RER, may bear ribosomes. Inner membrane: Provides nuclear support. Nuclear pores: Permit bidirectional exchange (mRNA out, proteins in). Function: Separates genetic material from cytoplasm while allowing communication.

35. Chromatin Material Chromatin = DNA + Histone Proteins. Two types: Euchromatin: Lightly stained, transcriptionally active. Heterochromatin: Densely stained, inactive region. Function: Carries genes → transmits hereditary traits.

36. Nucleolus Non-membranous, spherical body inside nucleus. Composed of rRNA and proteins. Functions: Synthesis of rRNA. Formation of ribosomal subunits. Regulation of cell proliferation.

37. DNA – Structure Deoxyribonucleic Acid (DNA) – double-helical molecule (Watson & Crick model). Composed of: Sugar (Deoxyribose) Phosphate group Nitrogenous bases (A, T, G, C) Base pairing: A–T (2 bonds), G–C (3 bonds). Function: Stores and transmits genetic information.

38. RNA Steps: Transcription: Occurs in nucleus. DNA → mRNA by RNA polymerase. Translation: Occurs in ribosome (cytoplasm). mRNA codons read by tRNA anticodons → polypeptide chain forms. DNA → mRNA → Protein

39. Cell Division Two main types: Mitosis: For somatic cell multiplication. Meiosis: For gamete formation. Purpose: Growth, repair, replacement, and reproduction.

40. Mitosis – Stages Prophase: Chromosomes condense, spindle forms. Metaphase: Chromosomes align at equator. Anaphase: Chromatids separate to poles. Telophase: Nuclear membrane reforms, cytokinesis completes. Result: 2 identical daughter cells (diploid).

41. Meiosis – Stages Occurs in gonads → gamete formation. Two successive divisions: Meiosis I: Reduction division (diploid → haploid). Meiosis II: Similar to mitosis. Result: 4 haploid daughter cells with genetic variation.

42. Apoptosis – Programmed Cell Death Definition: A genetically controlled mechanism of self-destruction eliminating unwanted or damaged cells. Features: Cell shrinkage, chromatin condensation, DNA fragmentation. Membrane remains intact (unlike necrosis). Phagocytosed by macrophages (no inflammation). Functions: Removal of defective cells. Embryonic development (digit separation). Regulation of immune system. Clinical Note: Abnormal apoptosis → cancer, autoimmune disease, neurodegeneration.

43. Stem Cells Definition: Undifferentiated cells capable of self-renewal and differentiation into specific cell types. Types: Embryonic stem cells: Pluripotent; can form any cell type. Adult stem cells: Multipotent; limited differentiation (e.g., bone marrow). Induced pluripotent stem cells (iPSCs): Reprogrammed adult cells. Functions: Tissue regeneration, repair, and cellular therapy.

44. Cell Aging Definition: Gradual decline in functional capacity due to molecular damage. Mechanisms: Decreased DNA repair efficiency. Accumulation of free radicals (oxidative stress). Telomere shortening after repeated cell division. Reduced mitochondrial function. Result: Loss of cell function → organ degeneration.

45. Cell Adaptation Cells adapt to stress via reversible changes:

46. Cell Degeneration and Necrosis Degeneration: Early reversible cellular injury. Causes: Hypoxia, toxins, infections. Types: Cloudy swelling Fatty degeneration Hydropic change Necrosis: Irreversible cell death due to membrane rupture & enzyme leakage. Types: Coagulative, Liquefactive, Caseous, Fat necrosis.

47. Comparison – Apoptosis vs Necrosis

48. Cell Junctions

49. Introduction Cells in the human body are not isolated units; they are organized into tissues. To function as a coordinated unit, cells must adhere, communicate, and exchange materials with one another. Cell junctions are specialized structures located on the cell membrane that link adjacent cells and facilitate communication and mechanical stability. Definition: Cell junctions are specialized intercellular connections that maintain structural integrity and enable communication between neighboring cells.

50. Importance of Cell Junctions Mechanical linkage between adjacent cells. Structural integrity of tissues (especially epithelial & cardiac). Regulation of paracellular transport (movement between cells). Cell-to-cell communication and coordination. Barrier formation to maintain polarity (apical vs. basolateral surfaces).

51. General Classification of Cell Junctions Based on structure and function, cell junctions are classified as:

52. Tight Junctions Located near the apical region of epithelial cells. Form a continuous belt-like seal around the cell. Proteins involved: Claudins and Occludins. Adjacent cell membranes are fused at multiple points forming a tight seal.

53. Tight Junctions – Functions Barrier Function: Prevent passage of water-soluble substances between cells (paracellular pathway). Example: Intestinal epithelium prevents leakage of digestive enzymes. Polarity Maintenance: Separate apical from basolateral surfaces, maintaining directional transport. Selective Permeability: Allows certain ions to pass (tissue-specific permeability). Clinical Note: Disruption → loss of epithelial barrier → intestinal leakage, inflammation, or edema.

54. Gap Junctions (Communicating Junctions) Specialized intercellular channels allowing direct communication. Formed by connexons, each made up of six connexin proteins. Connexons align to form a hydrophilic pore between adjacent cell membranes.

55. Gap Junctions – Functions Electrical coupling: Permit direct ion flow → enable synchronized contraction (cardiac & smooth muscle). Metabolic coordination: Allow passage of small molecules (cAMP, glucose, amino acids). Cell signaling: Facilitate spread of depolarization or secondary messengers. Homeostasis: Maintain ionic and metabolic balance among connected cells. Clinical Note: Defective connexins → conduction abnormalities, congenital cataracts, deafness.

56. Adhering Junctions (Anchoring Junctions) Located below tight junctions in epithelial cells. Provide mechanical attachment between cells. Types: Zonula Adherens (Adherens Junction) – belt-like connection. Desmosomes (Macula Adherens) – spot-like connection. Molecular Components: Cadherins (calcium-dependent adhesion molecules). Linked internally to actin or intermediate filaments via catenins and desmoplakins.

57. Adherens Junction Structure: Belt-like structure connecting actin filaments of neighboring cells. Maintained by E-cadherin proteins (require Ca²⁺). Functions: Maintain tissue stability and mechanical strength. Allow cells to resist shearing stress during movement or stretching (e.g., intestinal wall). Facilitate signal transduction between cells.

58. Desmosomes (Macula Adherens) Structure: Disc-shaped adhesive junctions located in epithelial and cardiac muscle cells. Composed of: Desmoglein & Desmocollin (cadherin family) Desmoplakin (links to intermediate filaments – keratin). Functions: Provide strong adhesion points between cells. Resist mechanical stress, maintaining tissue integrity. Clinical Correlation: Pemphigus vulgaris: Autoimmune attack on desmoglein → epithelial blistering. Arrhythmogenic right ventricular cardiomyopathy (ARVC): Mutation in desmosomal proteins → cardiac dysfunction.

59. Hemidesmosomes Structure: Found at the basal surface of epithelial cells attaching them to the basement membrane. Contain integrin proteins (instead of cadherins). Connect intermediate filaments (keratin) to basal lamina. Function: Anchor epithelial cells firmly to underlying connective tissue. Clinical Note: Bullous pemphigoid → autoimmune destruction of hemidesmosomes → skin blistering.

60. Distribution of Cell Junctions

61. Functional Integration In epithelial cells, junctions occur in specific sequence (apical to basal): Tight junction → 2. Adherens junction → 3. Desmosome → 4. Gap junction → 5. Hemidesmosome. Together they form the junctional complex maintaining structure, function, and communication.

62. Transport through Cell Membrane

63. Introduction The cell membrane is selectively permeable, meaning it allows only certain substances to pass through. The movement of materials between the intracellular fluid (ICF) and extracellular fluid (ECF) is essential for: Nutrient uptake Waste elimination Maintenance of ionic and osmotic balance These processes are collectively known as membrane transport mechanisms.

64. Classification of Transport Mechanisms Membrane transport mechanisms are broadly divided into three categories:

65. Factors Affecting Membrane Transport Lipid Solubility – higher solubility → faster diffusion. Size of the molecule – smaller molecules pass easily. Electrical charge – ions depend on electrochemical gradient. Carrier protein availability. Temperature – increased temperature enhances diffusion rate.

66. Passive Transport Definition: Movement of molecules across the cell membrane without energy expenditure, along the concentration or electrochemical gradient. Types: Simple Diffusion Facilitated Diffusion Osmosis

67. Simple Diffusion Definition: Random movement of molecules from a region of higher concentration to a region of lower concentration until equilibrium is achieved. Examples: O₂, CO₂, and lipid-soluble substances through the lipid bilayer. Movement of steroid hormones across the membrane. Factors affecting diffusion: Concentration gradient Temperature Membrane surface area Lipid solubility Membrane thickness

68. Fick’s Law of Diffusion Where: A = surface area of membrane ΔC = concentration difference P = permeability coefficient T = thickness of membrane Clinical Relevance: In pulmonary physiology, oxygen diffusion across alveoli follows Fick’s Law.

69. Facilitated Diffusion Definition: Movement of molecules along the concentration gradient through carrier proteins or channels without ATP use. Features: Saturable process (limited by carrier number). Specificity for particular molecules. Competition between similar molecules. Examples: Glucose transport into muscle and fat cells via GLUT-4 transporters (insulin-dependent). Transport of fructose via GLUT-5 in intestine.

70. Channel-Mediated vs Carrier-Mediated Diffusion Clinical Note: Cystinuria: Defect in carrier-mediated reabsorption of cystine → kidney stones.

71. Osmosis – Definition and Principle Definition: Movement of water molecules from a region of low solute concentration (high water potential) to high solute concentration (low water potential) across a semipermeable membrane. Key points: Driven by osmotic pressure. Water movement continues until osmotic equilibrium is reached.

72. Osmotic Pressure (π) The pressure required to stop osmosis is called osmotic pressure. Given by Van’t Hoff’s equation: π=CRT where C = concentration of solute R = gas constant T = absolute temperature Clinical Example: IV fluids must be isotonic to plasma (~300 mOsm/L) to prevent cell swelling or shrinkage.

73. Tonicity

74. Active Transport Definition: Movement of molecules against the concentration or electrochemical gradient, requiring energy (ATP) and carrier proteins. Features: Selective and saturable. Requires metabolic energy. Can maintain steep ion gradients (Na⁺, K⁺, Ca²⁺).

75. Types of Active Transport

76. Sodium–Potassium Pump (Na⁺–K⁺ ATPase) Structure: Enzyme located on cell membrane with α and β subunits. Maintains ionic gradients: 3 Na⁺ out / 2 K⁺ in per ATP molecule hydrolyzed. Functions: Maintains resting membrane potential. Prevents cell swelling by controlling osmotic balance. Provides electrochemical gradient for secondary transport. Clinical Note: Inhibited by Ouabain and Digoxin.

77. Calcium Pump (Ca²⁺ ATPase) Present in plasma membrane and sarcoplasmic reticulum. Actively transports Ca²⁺ out of cytoplasm, maintaining low intracellular Ca²⁺. In muscle, SERCA pump stores Ca²⁺ for contraction. Clinical Relevance: Impairment leads to disturbed muscle function or arrhythmias.

78. Hydrogen–Potassium Pump (H⁺–K⁺ ATPase) Located in gastric parietal cells. Pumps H⁺ into gastric lumen in exchange for K⁺. Essential for HCl secretion in stomach. Inhibitors: Proton pump inhibitors (PPIs) like Omeprazole → reduce gastric acidity (used in GERD, peptic ulcers).

79. Secondary Active Transport Definition: Transport of one solute against its gradient, coupled with another solute moving along its gradient (usually Na⁺). Types: Cotransport (Symport): Both move in same direction. Countertransport (Antiport): Move in opposite directions.

80. Examples of Secondary Active Transport Clinical Note: Na⁺–Ca²⁺ exchanger regulates intracellular Ca²⁺ in heart muscle → influences contractility.

81. Vesicular Transport Large molecules (proteins, lipids) are transported via membrane vesicles. Requires energy (ATP). Two main types: Endocytosis (into the cell) Exocytosis (out of the cell)

82. Endocytosis Definition: Process of engulfing extracellular material into the cell by vesicle formation. Types: Pinocytosis: Uptake of fluids (“cell drinking”). Phagocytosis: Engulfing solid particles (“cell eating”). Receptor-mediated endocytosis: Specific ligand binding (e.g., LDL–cholesterol uptake).

83. Phagocytosis Steps: Recognition and attachment of particle. Engulfment → phagosome formation. Fusion with lysosome → phagolysosome. Digestion by lysosomal enzymes. Exocytosis of debris. Examples: Neutrophils, macrophages → remove bacteria and dead cells. Clinical Note: Defective phagocytosis → chronic infections (e.g., Chronic granulomatous disease).

84. Exocytosis Definition: Process of releasing materials from cell into extracellular space via vesicle fusion with membrane. Examples: Neurotransmitter release at synapse. Hormone secretion (insulin, catecholamines). Enzyme release from glands. Mechanism: Vesicle moves to membrane. Fusion via SNARE proteins. Contents released.

85. Transcytosis Definition: Transport of macromolecules across a cell: endocytosis on one side → exocytosis on the other. Example: IgA transport across intestinal epithelium in newborns. Significance: Important in capillary endothelial transport and immune defense.

86. Comparison – Passive vs Active Transport

87. Clinical Correlations Cystic Fibrosis: Defective CFTR Cl⁻ channel → thick mucus in lungs & pancreas. Diabetes Mellitus: Impaired GLUT-4 function → reduced glucose uptake. Digitalis (cardiac drug): Inhibits Na⁺–K⁺ ATPase → increases intracellular Ca²⁺ → enhances myocardial contraction.

88. Homeostasis All living organisms are composed of one or more cells. The cell is the smallest unit capable of performing all vital physiological functions. It represents the basic structural and functional unit of the living body. Definition: Cell is defined as the structural and functional unit of the living body.

89. Introduction The internal environment of the body must remain constant for cells to function efficiently. Despite external changes (temperature, diet, stress), the body maintains internal equilibrium. This concept is called Homeostasis. Definition (Walter Cannon, 1932): Homeostasis is the maintenance of a stable internal environment in the body despite changes in the external environment.

90. Concept of Internal Environment Introduced by Claude Bernard (1857) → described milieu intérieur (internal environment). Refers to extracellular fluid (ECF) — the fluid surrounding the body’s cells. The ECF provides nutrients and removes waste; hence, its constancy is vital for cell survival. Composition of Internal Environment: Plasma (fluid portion of blood) Interstitial fluid (between tissue cells) Transcellular fluids (CSF, synovial, intraocular, etc.)

91. Importance of Homeostasis Homeostasis ensures: Stable environment for cellular metabolism. Optimal enzyme activity (pH, temperature, ion concentration). Regulation of body fluids, electrolytes, and gases. Prevention of pathological states (acidosis, dehydration, hypoxia). Example: Regulation of blood glucose, blood pressure, body temperature.

92. Homeostatic Control System Each homeostatic mechanism includes three key components:

93. Negative Feedback Mechanism Definition: A control mechanism that counteracts the initial change to restore stability. Most physiological systems operate via negative feedback. Acts like a self-regulating loop maintaining equilibrium. Examples: Regulation of body temperature. Control of blood glucose. Regulation of arterial blood pressure.

94. Example 1 – Temperature Regulation Stimulus: Rise in body temperature. Receptor: Thermoreceptors in skin/hypothalamus. Control Center: Hypothalamic thermostat. Effector Response: Sweating (evaporative cooling). Vasodilation (heat loss). Result: Body temperature returns to normal. Clinical Note: Failure → heatstroke or hypothermia.

95. Example 2 – Blood Glucose Regulation Stimulus: Rise in blood glucose after meal. Receptor & Control: β-cells of pancreas. Effector: Increased insulin secretion → promotes glucose uptake by cells. Result: Glucose returns to normal (90 mg/dL). Opposite condition: ↓ Blood glucose → α-cells release glucagon → glycogen breakdown → glucose ↑ again. Clinical Relevance: Disturbance → Diabetes Mellitus.

96. Example 3 – Arterial Blood Pressure Regulation Stimulus: Drop in BP. Receptor: Baroreceptors (carotid sinus, aortic arch). Control Center: Medullary vasomotor center. Effector: ↑ Heart rate, ↑ Vasoconstriction → BP normalizes. Negative Feedback Loop: Restores BP to set point. Clinical Note: Loss of baroreceptor reflex → postural hypotension.

97. Characteristics of Negative Feedback Reverses deviation from set point. Stabilizing effect – promotes equilibrium. Self-corrective mechanism. Operates continuously in dynamic balance. Analogy: Like a household thermostat controlling room temperature.

98. Positive Feedback Mechanism Definition: Mechanism that amplifies or enhances the initial change instead of opposing it. Less common in physiology. Usually occurs temporarily until a specific endpoint is reached.

99. Examples of Positive Feedback Parturition (Childbirth): Fetal head stretches cervix → Oxytocin release → ↑ uterine contractions → more stretch → cycle continues until birth. Blood Clotting: Platelet activation → more platelet aggregation → enhanced clot formation → stops once vessel is sealed. Generation of Nerve Impulse: Na⁺ entry depolarizes membrane → opens more Na⁺ channels → rapid depolarization → until action potential peaks.

100. Characteristics of Positive Feedback Reinforces deviation instead of correcting it. Destabilizing effect → not self-regulating. Must be terminated by an external event (e.g., delivery, clot completion). If unchecked → harmful: e.g., Circulatory shock → ↓ BP → ↓ tissue perfusion → further ↓ BP → death.

101. Feedforward Mechanism Definition: Anticipatory control mechanism where the body responds in advance to expected changes. Examples: Increased heart rate before exercise (due to anticipation). Salivation on seeing food (cephalic phase of digestion). Significance: Improves efficiency by reducing delay in response.

102. Concept of Set Point Every regulated variable has a set point or normal range around which it oscillates. Example: Body temperature: 37°C ± 0.5°C Blood glucose: 80–110 mg/dL pH: 7.35–7.45 The control system maintains these values via feedback loops. Dynamic equilibrium: small fluctuations occur but overall stability is maintained.

103. Hierarchy of Control Systems Homeostasis involves multiple overlapping control levels:

104. Neural and Hormonal Regulation 1. Nervous System: Provides rapid, short-term control (via reflexes). Example: Baroreceptor reflex for BP regulation. 2. Endocrine System: Provides slower, long-term control (via hormones). Example: Insulin-glucagon, ADH, thyroid hormones. Integration: Both systems interact → Neuroendocrine regulation (e.g., hypothalamus–pituitary axis).

105. Disturbances of Homeostasis When control mechanisms fail → disequilibrium or disease results Clinical Relevance: Physiology → explains normal function Pathology → explains failure of homeostasis

106. Concept of Allostasis Definition: The process by which the body achieves stability through change (adaptive adjustments beyond normal set points). Recognizes that the “set point” can shift during stress or disease. Example: Elevated BP during stress (temporary adaptive response). Significance: Chronic overactivation → “Allostatic load” → disease (hypertension, anxiety disorders).

107. Comparison – Negative vs Positive Feedback

108. Clinical Correlation – Shock Shock = failure of circulatory homeostasis. ↓ BP → ↓ perfusion → tissue hypoxia → further ↓ BP → vicious cycle (positive feedback). If unchecked → irreversible shock → death. Therapeutic Goal: Break the positive feedback by restoring perfusion (fluids, vasopressors).

109. Acid–Base Balance

110. Introduction Cellular metabolism continuously produces acids (CO₂, lactic acid, ketone bodies). The body must maintain a stable hydrogen-ion concentration for enzymes and biochemical reactions. Normal arterial blood pH = 7.35 – 7.45. Any deviation beyond this narrow range impairs body function and can be fatal. Definition: Acid–base balance is the maintenance of normal pH of body fluids through regulation of hydrogen ion concentration.

111. Significance of Maintaining pH Enzyme activity: Most enzymes function optimally near pH 7.4. Membrane integrity: pH changes affect ion channel and protein conformation. Electrolyte balance: H⁺ shifts influence K⁺ and Ca²⁺ distribution. CNS and Cardiac function: Severe acidosis or alkalosis causes coma or arrhythmias. Metabolic reactions: Require stable hydrogen ion concentration (~40 nEq/L).

112. Acids and Bases

113. Normal pH of Body Fluids

114. Sources of Acids in the Body Volatile acid: Carbonic acid (from CO₂ + H₂O). Eliminated by lungs (~15,000 mmol/day CO₂). Fixed acids: Produced by metabolism of proteins and phospholipids. Sulfuric acid, phosphoric acid (~70 mmol/day). Organic acids: Lactic, pyruvic, acetoacetic (acidosis in exercise or diabetes).

115. Mechanisms of pH Regulation The body maintains pH by three coordinated mechanisms:

116. Buffer Systems Definition: A buffer is a solution that resists pH change when small amounts of acid or base are added. Major physiological buffers: Bicarbonate buffer system (ECF) Phosphate buffer system (ICF and urine) Protein buffer system (plasma and cells) Hemoglobin buffer system (RBCs)

117. Bicarbonate Buffer System Most important ECF buffer. Components: H₂CO₃ / HCO₃⁻ pair. H₂CO₃ ↔ H⁺ + HCO₃⁻ Controlled by lungs (CO₂ ↔ H₂CO₃) and kidneys (HCO₃⁻ handling). Action when acid added: H⁺ combines with HCO₃⁻ → H₂CO₃ → CO₂ + H₂O (expired). Action when base added: OH⁻ combines with H₂CO₃ → HCO₃⁻ + H₂O.

118. Henderson–Hasselbalch Equation pKₐ of carbonic acid = 6.1. Normal ratio [HCO₃⁻ : H₂CO₃] ≈ 20 : 1 → pH 7.4. Clinical use: Helps interpret ABG values to identify acidosis or alkalosis.

119. Phosphate Buffer System Important in ICF and renal tubular fluid. Effective in pH range 6.8 – 7.4. Plays major role in renal H⁺ excretion and urine acidification.

120. Protein Buffer System Proteins (especially plasma albumin and globulins) have ionizable groups (–COOH, –NH₂). Act as amphoteric buffers (behave as acid or base). Contribute ~ 70% of total buffering capacity of plasma. Example: Hemoglobin in RBCs buffers carbonic acid by binding H⁺ to histidine residues.

121. Hemoglobin Buffer System Mechanism: CO₂ enters RBC → forms H₂CO₃ → H⁺ + HCO₃⁻. H⁺ binds to deoxy-Hb → HHb (hemoglobinic acid). HCO₃⁻ exchanges with Cl⁻ → chloride shift. Significance: Maintains blood pH and facilitates CO₂ transport from tissues to lungs.

122. Respiratory Regulation of pH CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻ Increased CO₂ → ↑ H⁺ → ↓ pH (acidosis) → ↑ ventilation → CO₂ elimination. Decreased CO₂ → ↓ H⁺ → ↑ pH (alkalosis) → ↓ ventilation. Time scale: Minutes. Example: Hyperventilation in anxiety → respiratory alkalosis.

123. Renal Regulation of pH Mechanisms: H⁺ Secretion in proximal and distal tubules. HCO₃⁻ Reabsorption – to replace filtered bicarbonate. Ammonium buffer system: NH₃ + H⁺ → NH₄⁺ (excreted). Phosphate buffering in urine. Time scale: Hours to days (long-term compensation).

124. Integration of Regulatory Mechanisms

125. Acid–Base Disturbances Four primary types:

126. Metabolic Acidosis Causes: Diabetic ketoacidosis, renal failure, diarrhea (loss of HCO₃⁻). Compensation: Kussmaul respiration (deep rapid breathing). ABG: ↓ pH, ↓ HCO₃⁻, ↓ Pco₂ (compensated).

127. Metabolic Alkalosis Causes: Vomiting (loss of HCl), excess antacid intake. Compensation: Hypoventilation → ↑ CO₂. ABG: ↑ pH, ↑ HCO₃⁻, ↑ Pco₂ (compensated).

128. Respiratory Acidosis Causes: Hypoventilation (COPD, asthma, respiratory depression). ABG: ↓ pH, ↑ Pco₂, ↑ HCO₃⁻ (chronic compensation). Treatment: Improve ventilation, administer O₂ carefully.

129. Respiratory Alkalosis Causes: Hyperventilation (anxiety, high altitude). ABG: ↑ pH, ↓ Pco₂, ↓ HCO₃⁻ (chronic compensation). Treatment: Rebreathing into paper bag or sedation to reduce ventilation.

130. Clinical Application: Arterial Blood Gas (ABG) Interpretation Determine pH (acidic/alkaline). Check Pco₂ (respiratory component). Check HCO₃⁻ (metabolic component). Assess compensation and clinical context.

131. Anion Gap Concept Anion Gap = [Na⁺] – ([Cl⁻] + [HCO₃⁻]) Normal = 8 – 16 mEq/L. Increased gap metabolic acidosis: due to unmeasured anions (lactate, ketones). Normal gap acidosis: loss of HCO₃⁻ (diarrhea, renal tubular acidosis).

132. Effects of pH Alterations

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