General, Cellular, and Systems Physiology Review

GENERAL & CELLULAR PHYSIOLOGY

  • Homeostasis

    • Definitions and terminology:
      • Claude Bernard: Coined the term "milieu interieu" (Internal environment).
      • Walter Cannon: Coined the term "homeostasis."
    • Control Systems:
      • Positive Feedback (Increase followed by increase): Increases the stimulus to drive a process to completion. Example: "CLAPS"
        • Clotting factors.
        • Ca entry into sarcoplasmic reticulum.
        • LH surge (triggers ovulation).
        • Action potential.
        • Parturition (childbirth).
        • Shock (vicious cycle of cardiovascular collapse).
      • Negative Feedback (Increase followed by decrease): Maintains stability by reversing a change. Example: Baroreceptor reflex for blood pressure regulation.
      • Feed-forward (Anticipatory changes): Adjustments made before the stimulus occurs. Examples:
        • Thinking about exercising leading to increased Respiratory Rate (RR) and Heart Rate (HR).
        • Body temperature regulation.
    • Assessment of Negative Feedback Effectiveness (Gain):
      • Formula: Gain=CorrectionError left after feedback\text{Gain} = \frac{\text{Correction}}{\text{Error left after feedback}}
      • If error left is high: Not a good control system.
      • If error left is zero: Gain is infinity (Example: Role of the kidneys in regulating BP).

  • Cell Membrane Lipids

    • Phospholipids:
      • Phosphatidylcholine/Lecithin/Dipalmitoyl phosphatidylcholine (DPPC): Essential component of lung surfactant.
      • Sphingomyelin: Found in nerves and surfactant. The Lecithin-Sphingomyelin ratio (L:S≥2)(L:S \geq 2) indicates adequate fetal lung maturity.
      • Phosphatidylserine (PS): Normally located on the inner surface of the cell membrane. If expressed on the outside, it acts as an "Eat-me signal," indicating the cell is undergoing apoptosis.
      • Phosphatidylinositol: Functions as a second messenger.
      • Cardiolipin: Specifically found in the mitochondria of the heart.
    • Glycolipids:
      • Cerebrosides: Located in the CNS.
      • Gangliosides: Located in the GIT. GM-1 gangliosides serve as receptors for the B fragment of the cholera toxin.
    • Sterols:
      • Cholesterol: Acts as a fluidity buffer to maintain membrane stability.

  • Membrane Fluidity and Fatty Acids:

    • Increased Fluidity (Good): Promoted by Unsaturated (Essential) fatty acids like Linoleic acid, Linolenic acid, Arachidonic acid, and Omega-3 fatty acids (abundant in fish).
    • Decreased Fluidity (Bad): Promoted by Saturated (Trans) fatty acids like Stearic acid and Palmitic acid (abundant in junk food).

  • Membrane Proteins:

    • Transmembrane Proteins:
      • Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): A chloride channel. Mutations lead to Cystic Fibrosis.
    • Peripheral Proteins:
      • RBC (Biconcave disc): Spectrin (mutations cause Elliptocytosis) and Ankyrin (mutations cause Spherocytosis).
      • Skeletal Muscle: Dystrophin (mutations cause Duchenne Muscular Dystrophy - DMD).
    • Lipid Anchored/GPI Anchored Proteins:
      • Present in RBCs (e.g., CD55 & CD59). Mutations cause Paroxysmal Nocturnal Hemoglobinuria (PNH).

  • Cell Organelles

    • Endoplasmic Reticulum (ER):
      • Rough ER: Granulated with ribosomes; functions in protein biosynthesis and folding (aided by chaperones). Involved in ER-associated degradation of misfolded proteins.
      • Smooth ER: No ribosomes; functions in drug detoxification (CYP450 in liver), calcium storage, and steroid biosynthesis (adrenal gland, testes, ovary).
    • Golgi Apparatus:
      • Cis end (receiving): Receives proteins for post-translational modification.
      • Trans end (releasing): Releases vesicles.
    • Lysosomes: Known as "suicidal bags" or "residual bodies." Contain acid phosphatase and acid hydrolase for acid-mediated destruction. Involved in autophagy during starvation.
    • Peroxisomes: Also called microbodies. Functions include oxidation of long-chain and very-long-chain fatty acids, generation/degradation of H2O2H_2O_2 by catalase, and synthesis of plasmalogens. Disorders include Zellweger syndrome and Refsum disease.
    • Mitochondria: Derived from the ovum (maternal inheritance). Contains circular double-stranded DNA (16,500 base pairs). Mutations occur at >10x the rate of nuclear DNA and affect high-metabolic organs (CNS, skeletal muscle, liver).
    • Nucleus: Contains chromosomes and chromatin (DNA + histones). Basic units are nucleosomes. Nuclear pore complex regulates movement via Importins (in) and Exportins (out).

  • Marker Enzymes:

    • Cell membrane: Na+- K+ ATPase\text{Na}^+ \text{- K}^+ \text{ ATPase}
    • Endoplasmic reticulum: Glucose-6-phosphatase
    • Golgi apparatus: Galactosyl transferase
    • Lysosomes: Acid phosphatase
    • Peroxisomes: Catalase
    • Mitochondria: ATP synthase
    • Nucleus: RNA polymerase

  • Cytoskeletal Filaments

    • Microtubules: Largest size. Included Kinesin (forward axonal transport: cell body to synapse) and Dynein (reverse axonal transport: synapse to cell body; also motility of cilia and sperm). Tubulin helps in chromosome movement during division. Inhibitors: Vincristine, Vinblastine, Colchicine.
    • Microfilaments: Smallest size. Types include Actin and Myosin. Used for muscle contraction (Sliding filament theory) and cell motility (Actin polymerization, e.g., Tumbling motility in Listeria).
    • Intermediate Filaments: Most abundant; act as tumor markers.
      • Keratin: Epithelial tissue (Epithelial carcinoma); Liver (Mallory-Denk bodies in Alcoholic liver disease).
      • Desmin: Muscle (Rhabdomyosarcoma).
      • Vimentin: Connective tissue/Fibroblasts (Mesenchymal tumors).
      • Glial Fibrillary Acidic Protein (GFAP): Astrocytes (Astrocytoma).
      • Lamin: Nucleus (Progeria/Premature aging).

  • Cellular Junctions

    • Zonula Adherens: Cadherins, calcium-dependent, linked to actin.
    • Desmosomes: Desmoglein and Desmocolins; linked to intermediate filaments. Seen in skin and cervix. Antibodies against desmoglein cause Pemphigus Vulgaris.
    • Zonula Occludens (Tight Junctions): Occludin and Claudin. Mutation in claudin causes Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
    • Gap Junctions: Composed of Connexons (1 Connexon=6 Connexins1 \text{ Connexon} = 6 \text{ Connexins}). Abundant in heart. Mutations cause cardiac arrhythmia or Charcot-Marie-Tooth disease.
    • Hemidesmosomes: Link cell to basal lamina; linked with intermediate filaments.
    • Focal Adhesions: Link cell to basal lamina; linked with actin.

  • Cellular Messengers & Receptors

    • Classes of Hormones:
      • Amino acid derivatives: Tyrosine gives rise to Catecholamines (Epinephrine, Norepinephrine, Dopamine).
      • Proteins: Insulin (51 AA51 \text{ AA}), Parathormone (84 AA84 \text{ AA}).
      • Cholesterol derivatives: Steroids (Aldosterone, Cortisol, Estrogen, Progesterone, Testosterone).
      • Vitamin derivatives: Vitamin A & D.
    • Receptor Types:
      • Cell Membrane: G-Protein Coupled (GPCR/7-transmembrane), Tyrosine Kinase (Insulin), Cytokine family (GH, Leptin, Erythropoietin).
      • Cytoplasmic: Steroid receptors (Glucocorticoids, Mineralocorticoids, Androgen, Vitamin D).
      • Nuclear: Estrogen, Vitamin A (RAR), Progesterone, Thyroid hormones.
    • Second Messengers:
      • cAMPcAMP: Vasopressin (V2V_2), Glucagon, Secretin.
      • IP3−DAG/CalciumIP_3-DAG/Calcium: Vasopressin (V1V_1), Endothelin (Vasoconstriction), Oxytocin (Uterine contraction).
      • cGMPcGMP: Nitric Oxide (Vasodilation), Natriuretic Peptides.

  • Membrane Transport

    • Passive Transport:
      • Simple Diffusion: Obeys Fick's Law (Flow proportional to area and gradient; inversely proportional to thickness). Example: Gas exchange in lungs.
      • Facilitated Diffusion: Uses carrier proteins like GLUT or Aquaporins. Follows saturation kinetics.
    • Active Transport:
      • Primary: Pumps like ATPases.
      • Secondary: Cotransporters (SGLT, Na-I symporter) or Exchangers (Cl−- HCO3−Cl^- \text{- HCO}_3^-).
    • Vesicular Transport: Requires calcium. Includes Exocytosis (SNARE proteins) and Endocytosis (Clathrin, cubilin).

  • Osmosis and Membrane Potentials

    • Osmolarity Formula: 2×Na+(meq/L)+0.055×Glucose(mg/dL)+0.36×Blood Urea Nitrogen(mg/dL)2 \times \text{Na}^+ (\text{meq/L}) + 0.055 \times \text{Glucose} (\text{mg/dL}) + 0.36 \times \text{Blood Urea Nitrogen} (\text{mg/dL})
    • Resting Membrane Potential (RMP):
      • Mechanism: Intracellular high K+K^+ diffuses out, leaving intracellular negative charge.
      • Hyperkalemia (↑Extracellular K+\uparrow \text{Extracellular } K^+): Decreases diffusion out, depolarizes cell, becomes more excitable.
      • Hypokalemia (↓Extracellular K+\downarrow \text{Extracellular } K^+): Increases diffusion out, hyperpolarizes cell, becomes less excitable.
      • Values: Neuron (−70 mV-70 \, \text{mV}), Skeletal muscle (−90 mV-90 \, \text{mV}), SA node (−60 to −40 mV-60 \text{ to } -40 \, \text{mV} - oscillatory).
    • Nernst Equation (Equilibrium Potential): Ex=±61log⁡CoCiE_x = \pm 61 \log \frac{C_o}{C_i}
      • Na+=+60 mVNa^+ = +60 \, \text{mV}
      • K+=−90 mVK^+ = -90 \, \text{mV}
      • Cl−=−70 mVCl^- = -70 \, \text{mV}
      • Ca2+=+130 mVCa^{2+} = +130 \, \text{mV}
    • Gibbs Donnan Effect: Non-diffusible protein anions inside the cell affect the distribution of diffusible ions.

  • Cellular Fluids

    • Total Body Water (TBW): 42 L42 \, \text{L} (60%60\% of body weight).
      • Intracellular (ICF): 28 L28 \, \text{L} (2/32/3 of TBW).
      • Extracellular (ECF): 14 L14 \, \text{L} (1/31/3 of TBW). Contains Plasma (3.5 L3.5 \, \text{L}) and Interstitial fluid (10.5 L10.5 \, \text{L}).
    • Indicators:
      • TBW: Deuterium, Tritium.
      • ECF: Inulin, sucrose, mannitol.
      • Plasma (PV): Albumin, Evan’s Blue dye.
      • Blood Volume (BV): PV/(1−Hematocrit)\text{PV} / (1 - \text{Hematocrit}) or Chromium tagged RBCs.
    • Dominant Ions:
      • ECF: Na+Na^+ (cation), Cl−Cl^- (anion).
      • ICF: K+>Mg2+K^+ > Mg^{2+} (cations), Phosphates/proteins (anions).

  • Water Loss and Darrow Yannet:

    • Sensible loss: Sweating (100 ml/day100 \, \text{ml/day}).
    • Insensible loss: Skin and lungs (600−700 ml/day600-700 \, \text{ml/day}).
    • Excessive NaCl Intake: ECF volume and osmolarity increase; ICF volume decreases and osmolarity increases (leading to Hypertension).

NERVE MUSCLE PHYSIOLOGY

  • Cells of the CNS

    • Neurons: Functional unit.
    • Glial Cells (1:101:10 ratio to neurons):
      • Astrocytes: Blood-brain barrier, produce neurotrophins, synaptic clearing of excess K+K^+ and neurotransmitters.
      • Oligodendrocytes: CNS Myelination.
      • Schwann cells: PNS Myelination.
      • Microglia: Phagocytosis.

  • Nerve Conduction

    • Nodes of Ranvier: Areas with no myelin and high Na+Na^+ channel density.
    • Myelin: Sphingomyelin lipid and Myelin basic protein (target in Multiple Sclerosis).
    • Factors Increasing Velocity (NCV): Higher axon diameter, myelination, increased temperature, high axonal resistance, or low membrane capacitance.
    • Action Potential Phase:
      1. Local potential (slow Na+Na^+ influx): −70 to −55 mV-70 \text{ to } -55 \, \text{mV}.
      2. Depolarization: Fast Na+Na^+ influx via voltage-gated channels.
      3. Repolarization: K+K^+ efflux.
      4. Hyperpolarization: Cl−Cl^- influx and slow closure of K+K^+ channels.
    • Refractory Periods:
      • Absolute (ARP): Threshold to initial 1/31/3 of repolarization; Na+Na^+ channels inactivated; no response.
      • Relative (RRP): 1/31/3 repolarization to the end; response only to maximum strength stimuli.

  • Nerve Fiber Classification:

    • Type AαA\alpha: Proprioception (Muscle spindle 1a1a, Golgi tendon 1b1b), Motor neurons. Velocity 120 m/s120 \, \text{m/s}.
    • Type AδA\delta: Fast/First pain.
    • Type CC: Slow/Second pain, postganglionic sympathetic. Unmyelinated, slowest velocity.

  • Nerve Injury and Regeneration

    • Wallerian (Distal) degeneration: Axon and myelin breakdown within 24 hours.
    • Retrograde (Proximal) degeneration: Chromatolysis (destruction of Nissl bodies) and nucleus displacement within 36 hours.
    • Regeneration: Rate of 1−3 mm/day1-3 \, \text{mm/day}. Tinel's sign (tingling on tapping) indicates regeneration.

  • Skeletal Muscle Structure

    • Sarcomere (Between 2 Z lines):
      • A-band: Myosin.
      • I-band: Actin.
      • H-band: Non-overlapping myosin.
      • M-line: Attaches myosin via myomesin.
    • Muscle Proteins:
      • Contractile: Actin, Myosin.
      • Supportive: Titin (elasticity, Z to M line), Nebulin (actin length), Desmin, Dystrophin, α\alpha-actinin.
      • Regulatory: Troponin, Tropomyosin.
      • Relaxation: SERCA (Ca2+Ca^{2+} ATPase pump).

  • Neuromuscular Transmission and Blockers

    • Process: Action potential arrives -> Ca2+Ca^{2+} influx -> Exocytosis of Acetylcholine (Ach) -> Ach binds nicotinic receptors -> Na+Na^+ influx -> End plate potential -> Muscle contraction.
    • Blockers/Toxins:
      • Tetradotoxin (pufferfish): Blocks Na+Na^+ channels.
      • Botulinum toxin: Blocks Ach release (Flaccid paralysis).
      • LEMS: Autoantibodies against voltage-gated Ca2+Ca^{2+} channels.
      • Myasthenia Gravis: Autoantibodies against nicotinic Ach receptors.
    • Calcium Channels: Dihydropyridine receptor (DHPR) in T-tubules mechanically interacts with Ryanodine receptor (RYR) on the SR. Overactive RYR causes Malignant Hyperthermia.

  • Muscle Contraction Mechanics

    • Cross bridge cycle:
      1. ATP binds myosin head.
      2. ATP hydrolysis (ATPaseATPase activity) cocks the head to 90∘90^\circ.
      3. Cross bridge forms with actin in the presence of Ca2+Ca^{2+}.
      4. Power stroke: Myosin head slides actin (releases ADP+PiADP+Pi) and moves to 45∘45^\circ.
      5. Detachment: Triggered by new ATP binding.
    • Length-Tension Relationship: Tension is directly proportional to actin-myosin overlap.
    • Skeletal Muscle Fiber Types:
      • Type I (Red): High myoglobin, aerobic, slow contraction, used for sitting.
      • Type IIb (White): Absent myoglobin, anaerobic (glycolysis), fast contraction, used for running.

  • Cardiac and Smooth Muscle

    • Cardiac: Functional syncytium via intercalated disks (Connexins/gap junctions). Calcium-induced calcium release (CICR). No summation or tetany due to long ARP.
    • Smooth: Involuntary. Uses Dense bodies instead of Z-lines. Calcium binds Calmodulin (no troponin). Latch bridge mechanism allows sustained contraction with low ATP in the GIT. "Synapse en passant" via varicosities.

  • Synaptic Transmission and Neurotransmitters

    • IPSP/EPSP: Fast EPSP (Na+/Ca2+Na^+/Ca^{2+} influx); Fast IPSP (Cl−Cl^- influx, K+K^+ efflux).
    • Renshaw cells: Use Glycine to provide feedback inhibition to α\alpha-motor neurons.
    • Neurotransmitters:
      • Norepinephrine: Locus coeruleus; arousal.
      • Dopamine: Nigrostriatal (motor), Mesolimbic (reward/addiction), Tuberoinfundibular (inhibits prolactin).
      • Serotonin: Raphe nucleus; wakefulness.
      • GABA: Major inhibitory NT in the brain. Tetanospasmin inhibits GABA (spastic paralysis).
      • Glutamate: Major excitatory NT; learning/memory in the hippocampus.
      • Glycine: Major inhibitory NT in spinal cord. Antagonist: Strychnine.
      • Nitric Oxide: Gaseous NT; learning/memory.

NEUROPHYSIOLOGY : PART 1

  • Sensory Physiology

    • Touch Receptors:
      • Meissner corpuscle: Discriminatory touch, stroking (Superficial, Rapidly adapting).
      • Merkel cells: Texture, edges/Braille (Superficial, Slowly adapting).
      • Pacinian corpuscle: Pressure, vibration (Deep, Rapidly adapting).
      • Ruffini endings: Skin stretch (Deep, Slowly adapting).
    • Pain Receptors: Free nerve endings (AδA\delta for fast pain; CC for slow pain).
    • Gate Control Theory: Non-painful sensations via AβA\beta fibers stimulate inhibitory neurons in the substantia gelatinosa, inhibiting projection neurons and reducing pain.
    • Somatosensory Pathways:
      • Dorsal Column: Proprioception, touch, vibration. Ipsilateral. Crosses at medulla.
      • Anterolateral: Pain, temperature. Contralateral. Crosses at spinal cord.

  • Vision

    • Retina Cells:
      • Ganglion cells: Only output of retina; only ones producing action potentials.
      • Amacrine/Horizontal cells: Lateral inhibition to sharpen signals.
      • Muller's cells: Supporting glial cells.
    • Physiology:
      • Rod in dark: cGMPcGMP-dependent Na+Na^+ channels open (depolarization).
      • Rod in light: Rodopsin activation -> Transducin -> Phosphodiesterase -> Decreased cGMPcGMP -> Na+Na^+ channels close (hyperpolarization).
    • LGB Layers: Ipsilateral eye (2, 3, 5); Contralateral eye (1, 4, 6).
    • Pathways: Magnocellular (Eye movements); Parvocellular (Color, fine detail).
    • Color Vision: LL cone (Red - defect is Protanopia), MM cone (Green - Deuteranopia), SS cone (Blue - Tritanopia).

  • Hearing

    • Organ of Corti: Hair cells rest on the basilar membrane. Depolarization occurs via bending towards the kinocilium (K+K^+ influx).
    • Basilar Membrane: Base (narrow, stiff) detects high frequency; Apex (broad, floppy) detects low frequency.
    • Auditory Pathway: Cochlea -> CN VIII -> Superior Olivary nucleus -> Lateral lemniscus -> Inferior colliculus -> Medial geniculate body (thalamus) -> Auditory cortex (Superior temporal gyrus).

  • Olfaction and Taste

    • Olfaction receptors: Bipolar neurons. Olfactory bulb contains Mitral/Tufted (excitatory, Glutamate) and Granule (inhibitory, GABA) cells.
    • Taste Receptors:
      • Salty: ENaCENaC (ionotropic).
      • Sour: ENaC,HCN,TRPENaC, HCN, TRP.
      • Sweet: T1R2,T1R3T1R2, T1R3 (metabotropic).
      • Umami: mGluR4,T1R1,T1R3mGluR4, T1R1, T1R3 (metabotropic).
    • Integrating center: Nucleus Tractus Solitarius in the medulla.

  • Motor Physiology

    • Motor Cortex: Area 4 (Primary execution); Area 6 (Premotor/Orientation and Supplementary/Bimanual coordination).
    • Reflexes:
      • Stretch Reflex: Monosynaptic. Receptor: Muscle spindle. Stimulus: Stretch. Center: Spinal cord. Afferent: Group IaIa and IIII.
      • Inverse Stretch Reflex (Lengthening reaction): Disynaptic. Receptor: Golgi tendon organ. Detects muscle tension. Causes relaxation.
      • Withdrawal Reflex: Polysynaptic. Flexion of injured limb and extension of the contralateral limb.

NEUROPHYSIOLOGY : PART 2

  • Cerebellum

    • Cerebellar Cells: 5 types. Inhibitory (Purkinje, Golgi, Stellate, Basket - all GABA) and Excitatory (Granule - Glutamate).
    • Nuclei: Dentate, Emboliform, Fastigial, Globose (DEFG).
    • Afferents: Climbing fibers (from Inferior Olive) and Mossy fibers.
    • Diseases: Ataxia, Hypotonia, Dysmetria, Intention tremor, Dysdiadochokinesia (inability to perform rapid alternating movements).

  • Basal Ganglia

    • Direct pathway: Inhibits GP interna -> facilitates movement.
    • Indirect pathway: Activates GP interna -> inhibits movement.
    • Lesion Effects:
      • Substantia nigra: Parkinsonism (resting tremor).
      • Caudate: Chorea.
      • Subthalamic nucleus: Hemiballismus.

  • Hypothalamus and Limbic System

    • Hypothalamic Nuclei:
      • Anterior (Heat), Posterior (Cold), Lateral (Feeding - Orexin), Ventromedial (Satiety), Suprachiasmatic (Master Clock).
    • Limbic Functions: Emotions (Amygdala), Memory (Hippocampus/Papez circuit).
    • Dominant Hemisphere (Left in 96% of right-handers): For language and speech.

  • Learning, Memory, and Speech

    • Consolidation: Takes place in the Hippocampus; lesions cause Anterograde Amnesia.
    • Wernicke-Korsakoff: Caused by alcohol-induced mammillary body degeneration.
    • Speech Areas:
      • Broca's (44, 45): Motor speech. Lesion = non-fluent aphasia.
      • Wernicke's (22): Comprehension. Lesion = fluent/sensory aphasia.
      • Arcuate Fasciculus: Connects the two. Lesion = conduction aphasia.

  • CSF and Sleep

    • CSF Production: 550 mL/day550 \, \text{mL/day}. Marker: β2\beta_2 transferrin.
    • Cerebral Blood Flow: 750 ml/min750 \, \text{ml/min}. Autoregulated between 65−140 mmHg65-140 \, \text{mmHg}.
    • EEG Waves: Alpha (Relaxed), Beta (Attention), Theta (Memory), Delta (Deep sleep).
    • Sleep Stages:
      • NREM Stage 2: K-complex and sleep spindles. Stage 3/4: Delta waves.
      • REM: Beta waves, muscle atonia, PGO spikes, dreaming. "REM-on" neurons use Acetylcholine.

RESPIRATORY PHYSIOLOGY : PART 1

  • Airway Generations

    • Weibel model: 23 generations.
    • Generations 0-16: Conducting airways (Dead space). Pseudostratified ciliated epithelium.
    • Generations 17-23: Alveolar airways (Gas exchange).
    • Pneumocytes:
      • Type I: Large, flat; for gas exchange.
      • Type II: Produce surfactant (stored as lamellar bodies); act as stem cells.
    • Surfactant: Lecithin/Sphingomyelin. Functions to decrease surface tension and prevent collapse (P=2T/rP = 2T/r).

  • Mechanics and Spirometry

    • IPP (Intrapleural Pressure): Normally −2.5 mmHg-2.5 \, \text{mmHg} at rest, dropping to −6 mmHg-6 \, \text{mmHg} during inspiration.
    • Compliance: ΔV/ΔP\Delta V / \Delta P. Highest during expiration (Hysteresis). Increased in Emphysema, decreased in Fibrosis.
    • Volumes:
      • TV=500 mLTV = 500 \, \text{mL}
      • RV=1.2 LRV = 1.2 \, \text{L}
      • FRC=ERV+RV=2.5 LFRC = ERV + RV = 2.5 \, \text{L} (Equilibrium point).
    • Obstructive Disease: FEV1/FVCFEV_1/FVC ratio is decreased. Dog-leg pattern on flow-volume loop.
    • Measurement of Dead Space: Single breath nitrogen (Anatomical); Bohr's equation (Physiological).

  • Perfusion and V/Q

    • Highest blood flow is at the base of the lung while the highest V/QV/Q ratio is at the apex (∼3.3\sim 3.3).
    • Hypoxia in the lung causes vasoconstriction (closes O2O_2-sensitive K+K^+ channels).
    • V/Q=0V/Q = 0: Shunt. V/Q=∞V/Q = \infty: Dead space (e.g., Pulmonary embolism).

RESPIRATORY PHYSIOLOGY : PART 2

  • Gas Transport

    • DLCO (Diffusing capacity for CO): Normal is 25 mL/min/mmHg25 \, \text{mL/min/mmHg}.
    • Oxygen dissociation curve:
      • Right Shift (decreased affinity): Increased pCO2pCO_2, acidity (↓pH\downarrow pH), increased temperature, high 2,3-DPG2,3 \text{-DPG}, exercise.
      • Left Shift: Alkalosis, fetal Hb, Carbon monoxide, hypothermia.
    • CO2 Transport: Mostly as bicarbonate (70%70\%). Chloride shift (Hamburger phenomenon) occurs in RBCs as HCO3−HCO_3^- exits.

  • Regulation of Respiration

    • Pre-Botzinger Complex: The pacemaker for respiration.
    • Centers: Pneumotaxic (limits inspiration), Apneustic (prolongs inspiration), DRG (ramp signal).
    • Reflexes:
      • Hering-Breuer Inflation: Inhibits inspiration to prevent overstretch.
      • J Receptor Reflex: Triggered by pulmonary edema; causes rapid breathing and bradycardia.
    • Chemoreceptors:
      • Central: Sensitive to arterial pCO2pCO_2 (via H+H^+ in CSF).
      • Peripheral (Carotid/Aortic bodies): Sensitive to hypoxia (↓pO2\downarrow pO_2).

  • Hypoxia Types:

    • Hypoxic: Low arterial pO2pO_2 (High altitude).
    • Anemic: Normal pO2pO_2, low Hb (CO poisoning).
    • Stagnant: Decreased blood flow (Ischemia).
    • Histotoxic: Cells cannot use O2O_2 (Cyanide).

CARDIOVASCULAR PHYSIOLOGY

  • Cardiac Action Potentials

    • SA Node (Pacemaker):
      • Phase 4 (Prepotential): Ca2+Ca^{2+} (Transient) and Na+Na^+ (Funny current/IfI_f) influx.
      • Phase 0: Ca2+Ca^{2+} (Long lasting) influx. No stable RMP.
    • Ventricle:
      • Phase 0: Na+Na^+ influx.
      • Phase 2 (Plateau): Ca2+Ca^{2+} influx equal to K+K^+ efflux.

  • Cardiac Cycle and Output

    • Cycle Duration: 0.8 s0.8 \, \text{s}. Systole: 0.3 s0.3 \, \text{s}; Diastole: 0.5 s0.5 \, \text{s}.
    • End Diastolic Volume (EDV): 120 mL120 \, \text{mL}. End Systolic Volume (ESV): 50 mL50 \, \text{mL}.
    • Stroke Volume (SV): 120−50=70 mL120 - 50 = 70 \, \text{mL}. Ejection Fraction: 55−60%55-60\%.
    • Heart Sounds: S1S_1 (Mitral/Tricuspid closure); S2S_2 (Aortic/Pulmonary closure); S3S_3 (Rapid filling).
    • Cardiac Output (CO): HR×SV≈5 to 5.5 L/minHR \times SV \approx 5 \text{ to } 5.5 \, \text{L/min}.

  • Blood and Hemodynamics

    • Erythropoiesis: Hb begins to synthesize in the Proerythroblast; nucleus is lost in the Reticulocyte. Erythropoietin produced by kidneys (85%85\%).
    • Blood Vessels: Aorta has max pressure and velocity; Capillaries have max surface area and minimum velocity (0.05 cm/s0.05 \, \text{cm/s}).
    • MAP (Mean Arterial Pressure): DBP+1/3 PP≈93 mmHg\text{DBP} + 1/3 \, \text{PP} \approx 93 \, \text{mmHg}.
    • Reynold’s Number (Re): Predicts turbulence. High Re = turbulent flow; Low Re = laminar flow.
    • Coagulation: Vit K dependent factors (II, VII, IX, X, Protein C and S).

GASTROINTESTINAL PHYSIOLOGY

  • Secretions and Hormones
    • Saliva: Hypotonic final secretion; contains salivary amylase and lingual lipase.
    • Gastric cells: Parietal cells (HCl and Intrinsic factor for B12B_{12}). Chief cells (Pepsinogen).
    • GI Hormones:
      • Gastrin: Increases acid; trophic effect on mucosa.
      • CCK: Gallbladder contraction; relaxation of sphincter of Oddi; slows gastric emptying.
      • Secretin: "Nature's antacid"; stimulates pancreatic juice rich in HCO3−HCO_3^-.
      • Ghrelin: Hunger hormone; orexigenic.
    • BER (Basal Electrical Rhythm): Duodenum (12/min12/\text{min}); Stomach (4/min4/\text{min}). Initiated by Interstitial cells of Cajal.

RENAL PHYSIOLOGY

  • Glomerular Filtration

    • Net Filtration Pressure: PC−(πC+Pb)=10 mmHgPC - (\pi C + Pb) = 10 \, \text{mmHg}.
    • GFR: 125 mL/min125 \, \text{mL/min}. Markers: Inulin (gold standard), Creatinine.
    • PCT: Maximum reabsorption site (100%100\% glucose and amino acids). Obligatory water reabsorption.
    • Loop of Henle: Descending limb (concentrating, permeable to water); Ascending limb (diluting, permeable to solutes). Uses Na/K/2ClNa/K/2Cl cotransporter (inhibited by Frusemide).
    • DCT: Significant site of Ca2+Ca^{2+} reabsorption (regulated by PTH and Vitamin D).
    • Collecting Duct: Principal cells (regulated by Aldosterone for Na+Na^+ reabsorption) and intercalated cells (acid-base balance). ADH acts on V2V_2 receptors to insert Aquaporin-2 for facultative water reabsorption.

  • Acid Base Balance

    • Normal pH: 7.35−7.457.35-7.45.
    • Metabolic Acidosis: Low pH, low HCO3−HCO_3^- (e.g., Diabetic ketoacidosis).
    • Respiratory Acidosis: High pCO2pCO_2 (e.g., COPD).
    • Anion Gap: Na+−(HCO3−+Cl−)=10 mEq/L\text{Na}^+ - (\text{HCO}_3^- + \text{Cl}^-) = 10 \, \text{mEq/L}.

ENDOCRINE PHYSIOLOGY

  • Pituitary and Thyroid
    • Growth Hormone: Increases insulin resistance, lipolysis, and protein synthesis. Indirectly works through IGF-1IGF\text{-}1.
    • Prolactin: Inhibited by Dopamine. Increased during pregnancy. Inhibits GnRHGnRH.
    • Thyroid Hormones: Iodide enters via NISNIS; organification occurs on thyroglobulin. T3T_3 is more potent with a shorter half-life (1 day1 \text{ day}) than T4T_4 (7 days7 \text{ days}).
  • Pancreas, Adrenal, and Calcium
    • Insulin: Depolarization of beta cells via closed KATPK_{ATP} channels leads to Ca2+Ca^{2+} influx and exocytosis. Increases GLUT-4GLUT\text{-}4 translocation.
    • Aldosterone: Acts on Principal cells to increase Na+Na^+ and water reabsorption; causes K+K^+ and H+H^+ excretion.
    • Cortisol: Hyperglycemic, catabolic in muscle, anabolic in liver, anti-inflammatory.
    • Calcium: PTHPTH increases serum calcium (increases bone resorption, renal reabsorption, and phosphate excretion). Calcitonin lowers serum calcium.

REPRODUCTIVE & EXERCISE PHYSIOLOGY, REGULATION OF BODY TEMPERATURE

  • Reproductive
    • Male: Puberty initiated by Kisspeptin. Sertoli cells (nurse cells) produce AMHAMH and InhibinInhibin. Leydig cells produce Testosterone. Erection is parasympathetic (NO/cGMPNO/cGMP); Ejaculation is sympathetic.
    • Female: Ovulation triggered by LHLH surge (24−36 hrs24-36 \text{ hrs} prior). Corpus luteum secretes Progesterone. hCG (super LHLH) maintains corpus luteum for 6 weeks6 \text{ weeks}.
  • Exercise
    • Energy: Phosphocreatine (8−10 s8-10 \, \text{s}) -> Glycogen-lactic acid (anaerobic) -> Aerobic system.
    • MET: 1 MET=250 ml/min1 \, \text{MET} = 250 \, \text{ml/min} (O2O_2 consumption).
  • Temperature Regulation
    • Hypothalamus: Anterior (response to heat, sweating); Posterior (response to cold, shivering).
    • Malignant Hyperthermia: Ryanodine receptor (RYRRYR) mutation; treat with Dantrolene sodium.