Chapter 2. Cellular Physiology

Part 1 | Cell Structure & Function

1 Learning Objectives

After this section you will be able to …

1. Sketch or label a typical human cell and name the function of every major organelle.
2. Explain how mitochondrial, endoplasmic-reticular, and cytoskeletal functions support movement, repair and energy supply—key pillars of physiotherapy.
3. Summarise the biochemical pathways of cellular metabolism (glycolysis → TCA → ETC) and relate ATP yield to exercise intensity.
4. Describe the steps of mitosis and meiosis, linking cell-cycle control to growth, healing and oncological precautions in rehabilitation.

2 The Cell: “Functional Unit of Life – Functional Unit of Rehab”

3 Cellular Metabolism – ATP Factory Tour

1. Glycolysis (cytosol)
   Glucose ➜ 2 Pyruvate + 2 ATP + 2 NADH (anaerobic or aerobic).
   • Physiotherapy link*: HIIT relies on rapid glycolysis; lactate threshold training delays fatigue.
2. Pyruvate Dehydrogenase Complex (mitochondrial matrix)
   Pyruvate ➜ Acetyl-CoA + NADH + CO₂
   • Thiamine-dependent*: patients with alcoholism—monitor for weakness.
3. TCA / Krebs Cycle
   Acetyl-CoA ➜ 3 NADH + FADH₂ + GTP + 2 CO₂
   • After 2 min of exercise*, this becomes core ATP provider.
4. Electron Transport Chain & Oxidative Phosphorylation
   NADH / FADH₂ donate e⁻ → O₂, pumping H⁺ → ATP synthase yields ~ 34 ATP.
   • Clinical: Hypoxia (SpO₂ < 90 %) impairs ETC – modify exercise intensity.
5. Anaerobic Fate
   NADH + Pyruvate ➜ Lactate via LDH—allows glycolysis to continue; lactate recycled (Cori cycle).
   • Post-exercise active recovery clears lactate via oxidation in slow-twitch fibres.

4 Cell Division

Cell-cycle checkpoints (p53, cyclins) are disrupted in cancer → PT must adjust intensity and infection control.

5 Integration Example – Tendon Healing Timeline

1. Inflammation (Day 0-3): Neutrophils & macrophages—lysosomal enzymes remove debris.
2. Proliferation (Day 3-21): Fibroblasts (RER ↑) synthesise type III collagen → converted to type I in maturation; vitamin C-dependent hydroxylation in rough ER & Golgi.
3. Maturation (Weeks 3-52): Cross-linking (lysyl oxidase) strengthens fibrils; progressive mechanical loading aligns fibres (Wolff’s law at cellular scale).

6 Self-Check Quiz (answers below)

1. Which organelle is expanded in hypertrophied muscle fibres to meet increased ATP demand?
2. State the net ATP yield from one glucose molecule under aerobic conditions.
3. During which mitotic phase do centromeres split?
4. Name the enzyme that cross-links collagen and the cofactor it requires.
5. Why does mitochondrial DNA mutate faster than nuclear DNA, and what implication does this have for ageing muscle?

Answers

1. Mitochondria.
2. Approximately 36–38 ATP (depending on shuttle pathway).
3. Anaphase.
4. Lysyl oxidase; requires copper.
5. Mitochondria reside in an ROS-rich environment and lack protective histones → mutations accumulate, reducing oxidative capacity and contributing to sarcopenia.

7 Practical / Lab Suggestions

8 Key Take-Home Messages

• Organelles cooperate like a factory; damage or adaptation in any compartment directly impacts rehabilitation outcomes.
• ATP supply pathways dictate exercise tolerance—understand where each fits on the intensity–time continuum.
• Cell division underlies healing and growth; PT must match load to the tissue’s biological timetable.

Part 2 | Membrane-Transport Mechanisms

1 Learning Objectives

1. Differentiate passive from active membrane transport and cite one physiotherapy-relevant example of each.
2. Describe the driving forces (concentration, electrical and hydrostatic gradients) behind diffusion and osmosis.
3. Explain primary- and secondary-active transport, naming the key pumps that maintain excitability of nerves and muscles.
4. Outline vesicular transport (endocytosis / exocytosis) and relate it to tissue repair, inflammation and drug delivery in rehabilitation.

2 Passive Transport

Fick’s Law (simple diffusion)  J=−D A ΔCΔxJ = -D,A,frac{ΔC}{Δx}J=−DAΔxΔC​

Greater surface (A) or smaller distance (Δx) boosts flux—reasoning behind incentive-spirometry post-surgery.

3 Active Transport

3.1 Primary-Active (ATP-driven)

3.2 Secondary-Active (Coupled-Carrier)

• Sodium–Glucose Co-Transporter (SGLT-1/2): Glucose reabsorption in gut & kidney—rehydration drinks exploit Na⁺-glucose co-transport.
• Na⁺/Ca²⁺ Exchanger (NCX): Removes Ca²⁺ post-contraction—digitalis inhibits Na⁺/K⁺-ATPase ⇒ ↑ intracellular Ca²⁺, ↑ inotropy; PT monitors HR in cardiac patients.

4 Vesicular Transport (Bulk)

5 Integrated Clinical Examples

6 Self-Check Quiz (answers below)

1. Why does simple diffusion rate plateau with membrane thickness but facilitated diffusion shows saturation?
2. State the effect of ouabain on resting membrane potential and muscle contractility.
3. Which vesicular transport process is up-regulated during macrophage activity in acute inflammation?
4. Explain how Na⁺/glucose co-transport enables oral rehydration therapy.
5. During NMES, why is extracellular K⁺ concentration critical for avoiding fatigue?

Answers

1. Simple diffusion is limited only by ∆C and distance; carriers in facilitated diffusion become saturated at high substrate concentration (Vmax).
2. Ouabain blocks Na⁺/K⁺-ATPase → depolarises cell (↑ Na⁺ inside); in heart, raises intracellular Ca²⁺ via NCX, increasing contractility.
3. Phagocytosis—a form of endocytosis mediated by actin.
4. Na⁺ pumped out by basolateral Na⁺/K⁺-ATPase keeps luminal [Na⁺] low; SGLT couples Na⁺ influx with glucose, pulling water osmotically into enterocytes, hydrating the body.
5. High extracellular K⁺ diminishes K⁺ gradient, delaying repolarisation → impulse failure. Adequate K⁺ prevents rapid fatigue during repetitive stimulation.

7 Key Take-Home Points

• Passive transport relies on gradients; active transport spends ATP or stored ion energy to move substances against gradients.
• Clinicians manipulate these mechanisms—breathing control, hydration, NMES, compression—to optimise patient outcomes.
• Understanding membrane dynamics prevents adverse events (e.g., hyponatremia, hyperkalemia) and explains therapeutic effects (muscle relaxation, airway clearance).

Part 3 | Cell Communication & Signalling

(focus: hormonal signalling & receptor types)

1 • Learning Objectives

After this part you will be able to …

1. Outline the basic routes of inter-cell communication (autocrine, paracrine, endocrine, neurocrine, juxtacrine).
2. Explain endocrine (hormonal) signalling from hormone synthesis to target-cell response, including feedback loops.
3. Classify receptors into four major families—ion-channel, G-protein-coupled, enzyme-linked, intracellular—and match each to representative ligands and second-messenger systems.
4. Relate signalling concepts to physiotherapy practice, such as exercise-induced hormonal changes, pharmacological precautions, and tissue-healing cascades.

2 • Communication Pathways Cheat-Sheet

3 • Hormonal Signalling – From Gland to Effect

1. Synthesis & Storage
   Peptide hormones (e.g., insulin) synthesised on RER, stored in vesicles;
   Steroid hormones (e.g., cortisol) synthesised from cholesterol on demand.
2. Release & Transport
   Stimuli (neural, humoral, hormonal) trigger exocytosis or diffusion.
   Carriers bind lipophilic hormones (cortisol–CBG) → longer half-life.
3. Reception
   Hormone binds specific receptor (cell-surface or intracellular).
4. Signal Transduction & Amplification
   Second messengers (cAMP, IP₃-Ca²⁺, cGMP) or direct gene activation.
5. Physiological Response
   Metabolic change, membrane transport, gene transcription, mitosis.
6. Feedback Regulation
   Negative feedback is most common (↑ cortisol → ↓ ACTH).
   Positive feedback rare (oxytocin in labour).

4 • Receptor Families & Key Features

Second-Messenger Mnemonic “CAMP-PI3-DAG-Ca”:
cAMP, PI3K-Akt, DAG/PKC, Ca²⁺/calmodulin—know which pathways your patient’s drugs or diseases influence.

5 • Applied Mini-Scenarios

6 • Self-Check Quiz (answers below)

1. Which receptor type is directly linked to rapid synaptic transmission in skeletal muscle?
2. Name the second messenger that increases intracellular Ca²⁺ via IP₃-mediated SR release.
3. Why can long-term glucocorticoid therapy impede tendon healing?
4. Exercise induces translocation of which glucose transporter to the sarcolemma?
5. Describe one positive-feedback hormonal loop relevant to childbirth.

Answers

1. Nicotinic acetylcholine receptor (ligand-gated ion channel).
2. Inositol-1,4,5-trisphosphate (IP₃).
3. Steroids bind intracellular GR → down-regulate collagen gene expression and inhibit fibroblast proliferation.
4. GLUT-4.
5. Uterine stretch → hypothalamus → posterior pituitary releases oxytocin, which intensifies contractions and further stretch.

7 • Key Take-Home Points

• Hormones are long-range messengers; receptors are the language translators.
• Understanding receptor families lets PTs predict drug interactions, exercise responses, and healing timelines.
• Exercise is a potent endocrine stimulus—myokines, catecholamines, IGF-1—harness them through programme design.