Cell Physiology & Homeostasis – Comprehensive Bullet Notes

Introduction to Physiology

• Physiology = study of physical & chemical mechanisms that underpin life.

• Coined by Claude Bernard; refined by Walter Cannon as homeostasis.

• Scope: viral, bacterial, cellular, plant, in/vertebrate, human.

• Key principle: survival demands stability of the internal milieu (blood, interstitial fluid). Deviations ➔ pathophysiology & disease.

• Etymology: homeo (same) + stasis (standing).

• Cells = fundamental living units; diverse in form/function but share basic characteristics & capacity for self-replication.

Clinical check-points

• Fasting blood glucose: 80\text{–}100\,\text{mg·dL}^{-1}. Persistent ↑ = diabetes → organ damage.

• Serum K⁺ has narrow limits; hypo/hyper-kalaemia → arrhythmia → death.

Pathophysiology

• Study of disordered function; explains disease mechanisms.

• Example: Diabetes mellitus

  • Type I = ↓ insulin production.

  • Type II = ↓ insulin responsiveness.

Homeostasis

• Definition: maintenance of a nearly constant internal environment.

• Fluid distribution:

  • Total body water ≈ $50\text{–}70\%$ BW (new-born ≈ $75\%$).

  • $\dfrac{2}{3}$ intracellular, $\dfrac{1}{3}$ extracellular.

• Disease = altered homeostasis.

Factors

1. Set-point (e.g. pH).

2. Mechanisms.

3. Sensors & effector signals.

4. System sensitivity (sensor nature, latency, effector speed).

Elements

• Receptor → Control centre (CNS/PNS) → Effector.

Examples

• Heat → skin thermoreceptors → hypothalamus → sweat glands.

• Pain/heat on hand → spinal reflex (withdrawal) + cortical awareness.

Control Mechanisms

• Negative feedback (most common)

  • Cold → TRH → TSH → T₃/T₄ → ↑ NST; hormones inhibit TRH/TSH when T° normalises.

  • ↑ BP → baroreceptors → vasodilation → ↓ BP.

• Positive feedback

  • Cervical stretch → oxytocin → uterine contractions → more stretch until delivery (self-limiting).

• Feed-forward/Adaptive

  • Anticipates change before disturbance affects parameter.

Physiological tolerances

• Plasma K⁺: mmol range.

• Blood pH: $7.35\text{–}7.45$; pH < 7 → incompatible with life.

Homeostasis of Body Fluid

• Water ≈ $60\%$ BW; varies with adiposity & age.

Cell Structure & Function

• Hierarchy: Cell → Tissue → Organ → System → Organism.

• Three regions: Plasma membrane, Cytoplasm, Nucleus.

• Two cell types: Prokaryote vs Eukaryote (true nucleus).

Cell Composition (Protoplasm)

• Water $70\text{–}85\%$: reaction medium.

• Proteins $10\text{–}20\%$

  • Structural (cytoskeleton).

  • Functional (enzymes).

• Lipids ≈ $2\%$: membranes, energy reserve.

• Carbohydrates ≈ $1\%$: energy; form glycoproteins.

• Ions (Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺, HCO₃⁻, PO₄³⁻, SO₄²⁻).

Cytoplasmic Organelles

• Endoplasmic Reticulum (ER) – network continuous with nuclear envelope.

  • Rough ER (ribosomes): protein synthesis/processing.

  • Smooth ER: lipid & steroid synthesis; detox (liver); sarcoplasmic reticulum stores Ca²⁺ in muscle.

• Ribosomes – rRNA + protein; translate mRNA.

• Golgi Apparatus – cis → medial → trans cisternae; modify, sort, package proteins/lipids for secretion or lysosomes.

• Mitochondria – double membrane, cristae; oxidative phosphorylation produces $90\text{–}95\%$ cellular ATP; own mtDNA/RNA (e.g. cardiomyocyte ≈ 40 % volume).

• Lysosomes – Golgi-derived vesicles w/ hydrolytic enzymes, lysozyme, lysoferrin; intracellular digestion (phago- & autophagy).

  • Tay–Sachs: absence of Hexosaminidase A → GM₂ ganglioside accumulation → neuro-degeneration (seizures, blindness, death < 5 y).

• Peroxisomes (microbodies) – ER-derived; oxidative enzymes (catalase, peroxidases) generate H₂O₂ for detox & lipid metabolism.

  • Zellweger syndrome: peroxisome biogenesis defect.

• Cytoskeleton

  • Microfilaments (actin, 7 nm): motility, microvilli core.

  • Intermediate filaments (10 nm): cell-type specific (keratin, neurofilament); tensile strength; link via desmosomes/hemidesmosomes.

  • Microtubules (tubulin, 25 nm): vesicle transport (kinesin ↑, dynein ↓), mitotic spindle, cilia/flagella motion.

• Cellular projections

  • Cilia:

  • Primary (non-motile) vs secondary (motile; dynein arms).

  • Kartagener’s (Primary ciliary dyskinesia): absent dynein → infertility (immotile sperm), recurrent lung infections (↓ mucociliary clearance).

  • Microvilli (1–3 µm): ↑ surface area (intestinal epithelium, renal PT).

  • Stereocilia (≈ 120 µm): long microvilli; epididymis & inner-ear hair cells.

• Nucleus

  • Double membrane; perinuclear cisternae; nuclear pores (mRNA export).

  • Nucleolus – rRNA synthesis & ribosome assembly.

  • Chromatin – DNA + histones; condenses to chromosomes during mitosis.

Membrane Physiology

Plasma Membrane

• $\text{Thickness}\approx5\,\text{nm}$; lipid bilayer with embedded proteins & carbohydrates (glycocalyx).

• Composition: Proteins 55 %, Phospholipids 25 %, Cholesterol 13 %, Other lipids 4 %, Carbohydrates 3 %.

• Phospholipids = amphipathic; sphingolipids & glycerophospholipids.

• Functions: selective permeability, ionic gradients, signaling, adhesion, enzymatic activity, antigenicity, shape.

Membrane Proteins

• Integral (transmembrane) – channels, carriers, receptors.

• Peripheral – loosely attached; enzymes, signal transducers.

• Lipid-anchored – covalently linked via lipid moiety.

Fluidity determinants

• Temperature: ↑T → ↑ fluidity.

• Cholesterol: buffers; ↑ fluidity at low T (prevents packing), ↓ at high T (restrains movement).

• Lipid composition: ↑ unsaturated FA (kinks) → ↑ fluidity.

Membrane Junctions

Membrane Transport Proteins

• Aquaporins (AQP) – water channels; AQP2 (apical CD, ADH-regulated), AQP3/4 (basolateral). Aquaglyceroporins transport glycerol, urea, CO₂, NH₃.

• Ion channels – selective/non-selective; characterised by conductance (pS) & gating (leak, ligand-, voltage-, mechano-).

• Solute carriers (SLC)

  • Uniport (GLUT 1–4).

  • Symport (NKCC2; SGLT1/2).

  • Antiport (NHE-1 Na⁺/H⁺ exchanger).

• ATP-dependent transporters

  • P-type (Na⁺/K⁺-ATPase, Ca²⁺-ATPase).

  • V-type (H⁺ pumps in lysosome, renal acidification).

  • F-type (mitochondrial ATP synthase).

  • ABC family (CFTR, MDR, bile salt export).

Transport Processes

Passive (no ATP, down gradient)

1. Osmosis – water via AQP from ↓ solute → ↑ solute.

   • Osmotic pressure $\pi$ by Van’t Hoff: $\pi = n C R T$.

   • Osmolarity (mOsm·L⁻¹) vs Osmolality (mOsm·kg H₂O⁻¹, temperature-independent, preferred clinically).

   • Tonicity: hypo- (cell swell), hyper- (shrink), iso- (no net volume change).

   • Gibbs–Donnan: impermeant anion ↑ intracellular osmolality → water influx; countered by Na⁺/K⁺-ATPase, RVD/RVI mechanisms.

2. Diffusion – random motion; Fick’s law $J = -D A \dfrac{\Delta C}{\Delta x}$; $D \propto \dfrac{T}{\eta r}$.

   • Simple vs Facilitated (carrier-mediated, saturable).

3. Filtration – bulk flow driven by hydrostatic pressure (kidney glomerulus). Governed by Starling forces across capillaries.

Active (ATP or ion gradient, uphill)

1. Primary – direct ATP hydrolysis (Na⁺/K⁺-ATPase pumps 3 Na⁺ out / 2 K⁺ in, establishes $-70\,\text{mV}$ Vm & osmotic balance).

2. Secondary – couples to gradient of another ion (usually Na⁺)

   • Cotransport (SGLT: Na⁺ + glucose in same direction).

   • Counter-transport (Na⁺/Ca²⁺ exchanger).

Vesicular (Bulk) Transport

• Endocytosis

  • Phagocytosis (large particles; macrophage).

  • Pinocytosis (fluid uptake; endothelial vesicles 100–200 nm).

  • Receptor-mediated (clathrin-coated vesicles; LDL, transferrin).

• Exocytosis (SNARE-mediated)

  • Constitutive (plasma cells—Ig, fibroblasts—collagen).

  • Regulated (endocrine, neurons; Ca²⁺-triggered).

Epithelial Transport

• Paracellular (between cells via tight junctions; passive; limited by claudins).

• Transcellular (across apical ✓ cytosol ✓ basolateral; uses channels, pumps, carriers).

  • Example: Na⁺-driven glucose uptake in enterocyte; Na⁺/K⁺-ATPase on basolateral side maintains gradient.

Cellular Communication

• Gap junctions – direct cytoplasmic continuity via connexons.

• Signal transduction pathway: signaling cell → ligand → receptor → intracellular cascade → target proteins → response.

Modes of inter-cell signaling

Receptor Classes

1. Ligand-gated ion channels – rapid, synaptic; ACh-nicotinic (Na⁺/K⁺), GABAᴀ (Cl⁻).

2. G-protein-coupled receptors (GPCR) – serpentine 7-TM; activate Gα/βγ ➔ adenylyl/guanylyl cyclase, phospholipase C, ion channels.

3. Enzyme-linked receptors – intrinsic or associated kinase/guanylyl activity (RTK: insulin, EGF; Ser/Thr kinase: TGF-β; receptor GC: ANP; JAK-STAT cytokine receptors).

4. Nuclear receptors – intracellular; ligand (steroid, thyroid, vitamin D, retinoic acid) crosses membrane, binds receptor, alters gene transcription.

Ethical & Practical Implications

• Understanding homeostatic thresholds guides clinical management (e.g. fluid therapy: isotonic NSS in transfusion).

• Membrane transporters are drug targets (e.g. SGLT2 inhibitors in diabetes; CFTR in cystic fibrosis).

• Genetic defects in organelles (Tay–Sachs, Zellweger, Kartagener’s) illustrate interplay of cell physiology & disease.

Key Equations & Constants

• Van’t Hoff: $\pi = n C R T$.

• Fick: $J = -D A \dfrac{\Delta C}{\Delta x}$.

• Diffusion coefficient (Stokes–Einstein): $D = \dfrac{k_B T}{6\pi \eta r}$.

• Resting membrane potential chiefly set by Na⁺/K⁺-ATPase & K⁺ leak channels (Goldman equation not shown).

High-Yield Numbers

• Blood pH $7.35\text{–}7.45$; < 7 fatal.

• Plasma Na⁺ ≈ 142\,\text{mEq·L}^{-1} vs ICF ≈ 10\,\text{mEq·L}^{-1}.

• Plasma K⁺ ≈ 4\,\text{mEq·L}^{-1} vs ICF ≈ 140\,\text{mEq·L}^{-1}.

• Osmolarity of body fluids ≈ 300\,\text{mOsm·L}^{-1}.

• Na⁺/K⁺-ATPase stoichiometry: $3\,\text{Na}^+<em>{out} : 2\,\text{K}^+</em>{in}$ per ATP.

Quick Pathology Links

• Hypo-/hyper-kalaemia → arrhythmias.

• Cystic fibrosis: CFTR (ABC transporter) mutation → defective Cl⁻/fluid secretion.

• Cholesterol excess: membrane fluidity alteration & atherogenesis.

End of comprehensive study notes for Cell Physiology & Homeostasis