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Guyton & Hall - Complete Chapter Study Guide

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UNIT III: THE HEART

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Chapter 9 - Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves

Core Concept

Cardiac Muscle Anatomy

• Three types: atrial muscle, ventricular muscle, specialized excitatory/conductive fibers
• Cardiac muscle is striated like skeletal muscle with actin and myosin filaments
• Fibers are arranged in a latticework (syncytium)
• Intercalated discs contain gap junctions (low electrical resistance) - allow action potentials to spread freely across the entire atrial or ventricular mass (functional syncytium)
• Two functional syncytia: atrial syncytium + ventricular syncytium - separated by fibrous tissue (AV valve ring)
• Left ventricle contracts in a twisting/wringing motion (outer layer spirals left, inner layer spirals right) - enhances ejection and "untwisting" aids rapid filling

Cardiac Action Potential

• Ventricular action potential = ~105 mV; resting membrane potential = -85 to -90 mV
• 5 phases:
  • Phase 0: Rapid depolarization - fast Na+ channels open
  • Phase 1: Brief early repolarization - K+ efflux
  • Phase 2 (PLATEAU): Ca2+ influx through L-type channels + reduced K+ permeability - unique to cardiac muscle; lasts 0.2-0.3 sec
  • Phase 3: Rapid repolarization - Ca2+ channels close, K+ channels open
  • Phase 4: Resting potential (-80 to -90 mV)
• The plateau makes cardiac contraction last ~15x longer than skeletal muscle
• Conduction velocity: 0.3-0.5 m/sec in atrial/ventricular muscle; 4 m/sec in Purkinje fibers
• Refractory period: ventricles = 0.25-0.30 sec; atria = 0.15 sec

Excitation-Contraction Coupling

• Ca2+ enters from TWO sources: (1) release from sarcoplasmic reticulum, AND (2) from T-tubule L-type channels (extracellular Ca2+)
• Cardiac contraction depends on extracellular Ca2+ (unlike skeletal muscle)
• T-tubules are larger in cardiac muscle and contain mucopolysaccharides (Ca2+ reservoir)
• After action potential: Ca2+ pumped back by SERCA (sarcoplasmic reticulum Ca2+ ATPase) + Na-Ca exchanger
• Cardiac muscle cannot undergo tetanic contraction (long refractory period = protective)

The Cardiac Cycle (Wiggers Diagram) ⭐⭐⭐

1. Atrial systole (last 1/3 of diastole): pumps ~20-30% of ventricular fill; a-wave
2. Isovolumic contraction: all valves closed; pressure rises to aortic diastolic pressure (~80 mmHg); no volume change
3. Ejection phase: aortic valve opens; SV ejected; systolic pressure peaks ~120 mmHg
4. Isovolumic relaxation: all valves closed; pressure drops
5. Rapid filling (first 1/3 of diastole): AV valves open; 70% of fill here
6. Diastasis (middle 1/3): slow passive filling
7. Atrial systole (last 1/3): completes fill

• a-wave: atrial contraction (RA +4-6 mmHg, LA +7-8 mmHg)
• c-wave: AV valve bulging into atria at start of ventricular contraction
• v-wave: venous filling of atria while AV valves closed during ventricular systole

Ventricular Volumes

• End-diastolic volume (EDV): ~120 ml
• End-systolic volume (ESV): ~40-50 ml (can fall to 10-20 ml with strong contraction)
• Stroke volume (SV): EDV - ESV = ~70 ml
• Ejection fraction (EF): SV/EDV = ~60%

Heart Valves

• AV valves (tricuspid, mitral): prevent backflow during systole - papillary muscles + chordae tendineae prevent inversion
• Semilunar valves (aortic, pulmonary): prevent backflow during diastole
• Close/open passively based on pressure gradients

Heart Sounds

• S1 (lub): AV valve closure at start of systole - low pitch, long
• S2 (dub): Semilunar valve closure at end of systole - high pitch, short snap
• S3: Rapid ventricular filling (normal in children; pathological in adults - heart failure)
• S4: Atrial contraction into stiff ventricle (always pathological)

Work Output of the Heart

• Left ventricle does ~6x more work than right ventricle (higher pressures)
• Stroke work = stroke volume × mean arterial pressure
• Frank-Starling Law: Greater stretch of cardiac muscle (increased EDV) → greater force of contraction → increased stroke volume
  • Mechanism: stretched sarcomeres have more optimal actin-myosin overlap
  • This allows the heart to automatically match cardiac output to venous return

Metabolic Features

• Heart uses ~70% of delivered O2 (highest extraction ratio of any organ)
• Normally uses fatty acids as primary fuel (~70%); also glucose, lactate
• Coronary blood flow ∝ cardiac metabolic rate

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Chapter 10 - Rhythmical Excitation of the Heart

The Conduction System ⭐⭐⭐

• Located: upper posterior right atrium near opening of superior vena cava
• Natural pacemaker - fires at 60-100 bpm (intrinsic rate ~100, vagal tone slows to ~72)
• Resting potential only reaches -55 to -60 mV (NOT fully polarized like ventricular muscle)
• Self-excitation mechanism (spontaneous depolarization = automaticity):
  1. After action potential, K+ channels close → membrane drifts toward threshold
  2. Inward Na+ "funny current" (If) + Ca2+ influx drives depolarization
  3. Threshold = -40 mV → action potential fires
  4. Process repeats

• Anterior interatrial band (Bachmann's bundle): to left atrium
• 3 internodal pathways (anterior, middle, posterior): to AV node
• Conduction velocity ~1 m/sec in these specialized pathways (vs. 0.3 m/sec in regular atrial muscle)

• Located: posterior wall of right atrium behind tricuspid valve
• Delays impulse by 0.09-0.13 sec (total atrial-to-ventricular delay ~0.16 sec)
• Why delay? Allows atria to empty into ventricles before ventricular contraction
• Very small, slowly conducting fibers in transitional zone
• Intrinsic escape rate: 40-60 bpm

• AV bundle = only electrical connection between atria and ventricles
• Bundle branches: Right and Left (left divides into anterior and posterior fascicles)
• Purkinje fibers: fastest conduction in the heart = 4 m/sec (vs. 0.3-0.5 in regular muscle)
• Allow near-simultaneous activation of entire ventricular wall (from inside out = endocardium first)
• Intrinsic escape rate of Purkinje fibers: 15-40 bpm

Pacemaker Hierarchy (Important for Escape Rhythms!)

Hyperpolarization and Self-Excitation

Autonomic Effects

• Sympathetic (NE, via β1): increases heart rate (SA node fires faster), increases conduction velocity, increases contractility
• Parasympathetic (ACh, via M2): decreases heart rate (hyperpolarizes SA node via K+ channels), slows AV conduction

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Chapter 11 - Fundamentals of Electrocardiography

ECG Basics ⭐⭐⭐

• Measures electrical activity of the heart from the body surface
• Standard paper speed: 25 mm/sec
• Small box = 1 mm = 0.04 sec; large box = 5 mm = 0.20 sec
• Amplitude: 10 small boxes = 1 mV

Normal ECG Waves

Key Intervals

Why T Wave is Same Direction as QRS

• Ventricles repolarize in the opposite sequence from depolarization (endocardium repolarizes last even though it depolarizes first, because outer layers have shorter action potentials)
• Endocardium depolarizes first (Purkinje fibers), but repolarizes last → repolarization proceeds from epicardium to endocardium → same direction as depolarization vector → T wave is positive in leads where R wave is positive

ECG Leads (Standard)

• Limb leads I, II, III (Einthoven's triangle)
• Lead II = most commonly used to assess rhythm (P waves most visible)
• Lead I: between right arm (-) and left arm (+)
• Lead II: between right arm (-) and left leg (+)
• Lead III: between left arm (-) and left leg (+)

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UNIT IV: CIRCULATION

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Chapter 14 - Overview of the Circulation: Pressure, Flow, and Resistance

Functional Organization

1. Pulmonary circulation: low pressure, short, entire cardiac output
2. Systemic circulation: high pressure, long, same total cardiac output

Normal Pressures ⭐⭐

Ohm's Law Applied to Circulation ⭐

• F = blood flow (L/min)
• ΔP = pressure difference
• R = resistance

• Resistance is inversely proportional to the 4th power of radius - most important!
• Doubling radius decreases resistance 16-fold and increases flow 16-fold

Total Peripheral Resistance (TPR)

• Arterioles = 47% of total resistance (main site of regulation)
• Capillaries = 27%
• Large arteries = 19% (minor)
• Veins = 7%

Blood Flow Distribution (at rest) ⭐

Velocity of Blood Flow

• Velocity (v) = Flow (F) / Cross-sectional area (A)
• Aorta: ~33 cm/sec
• Capillaries: ~0.3 mm/sec (very slow for gas/nutrient exchange)
• Blood stays in capillaries only 1-3 seconds - enough for diffusion

Three Principles of Circulatory Function

1. Blood flow to tissues is controlled by local tissue needs (metabolic autoregulation)
2. Cardiac output = sum of all local tissue blood flows (tissues control CO, not the heart!)
3. Arterial pressure is controlled independently (different mechanisms from flow control)

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Chapter 15 - Vascular Distensibility and Functions of the Arterial and Venous Systems

Vascular Compliance

• Compliance (C) = ΔVolume / ΔPressure
• Veins are ~8x more compliant than arteries → veins act as reservoir (hold ~64% of blood volume)
• Arterial compliance = dampens pulsatile pressure → converts pulsatile to smooth flow in capillaries

Pulse Pressure ⭐

• Increased SV → increased pulse pressure
• Decreased compliance (e.g., arteriosclerosis) → increased pulse pressure
• Clinical conditions affecting pulse pressure:
  • Aortic stenosis: narrow opening → decreased pulse pressure (slow rise, slow fall)
  • Aortic regurgitation: backflow → very wide pulse pressure; no dicrotic notch; diastolic can approach 0
  • Patent ductus arteriosus: blood runs off into pulmonary artery → low diastolic pressure → wide pulse pressure

Delayed Compliance (Stress Relaxation)

Mean Arterial Pressure (MAP)

Venous Return and Venous Pressure

• Mean systemic filling pressure (~7 mmHg): pressure throughout the entire circulation when heart is stopped
• Central venous pressure (right atrial pressure) = ~0 mmHg normally
• Factors that increase venous return: sympathetic venoconstriction, increased blood volume, skeletal muscle pump, respiratory pump (inspiration → negative thoracic pressure)

Capillary Pulse Pressure Transmission

1. Arterial compliance absorbs pulse energy
2. Resistance in arterioles dissipates energy

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Chapter 16 - The Microcirculation and Lymphatic System

Microcirculation Components

• Also: arteriovenous shunts (bypass capillaries in skin - important for temperature regulation)

Vasomotion

• Capillary blood flow is intermittent (not continuous)
• Metarterioles and precapillary sphincters alternately contract/relax = vasomotion
• Controlled mainly by tissue O2 concentration: low O2 → sphincters open → more flow

Capillary Fluid Exchange (Starling Forces) ⭐⭐⭐

• Pc = capillary hydrostatic pressure (tends to push fluid OUT)
• Pi = interstitial hydrostatic pressure (opposes filtration; normally slightly negative ≈ -3 mmHg)
• πp = plasma colloid osmotic pressure (oncotic pressure; holds fluid IN) = ~28 mmHg
• πi = interstitial colloid osmotic pressure (holds fluid OUT) = ~8 mmHg

Causes of Edema ⭐

1. Increased capillary hydrostatic pressure (heart failure, venous obstruction)
2. Decreased plasma oncotic pressure (hypoalbuminemia from liver disease, malnutrition)
3. Increased capillary permeability (inflammation, burns)
4. Lymphatic obstruction (elephantiasis, surgery)

The Lymphatic System

• Returns excess filtered fluid + plasma proteins to circulation
• Lymph flow: ~2-3 L/day
• Right lymphatic duct + thoracic duct → subclavian veins
• Lymph contains large proteins that cannot be reabsorbed into capillaries
• Pumped by: intrinsic smooth muscle contractions in lymph vessels + skeletal muscle compression + respiratory movements
• Safety factor against edema: lymph flow can increase 10-50x before edema becomes clinically apparent

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Chapter 17 - Local and Humoral Control of Tissue Blood Flow

Autoregulation

Two Theories of Local Blood Flow Control

• Metabolic activity → vasodilator metabolites released → arteriolar dilation
• Key vasodilators: adenosine, CO2, lactic acid, K+ ions, H+, histamine, ATP
• Adenosine is especially important in the heart (coronary vasodilation)
• Low O2 → adenosine + lactic acid release → local vasodilation

• Low O2 → vascular smooth muscle cannot maintain contraction → vessels dilax
• Both mechanisms likely work together

Reactive Hyperemia

• Brief occlusion → O2 deficit accumulates → vasodilators accumulate
• When occlusion released → massive flow increase (3-4x normal) for time proportional to occlusion duration
• Important in coronary circulation

Active Hyperemia

• Increased tissue activity → increased blood flow
• Flow increases in proportion to metabolic rate

Blood Flow to Different Organs (Resting)

Humoral Vasoconstrictor Agents

• Norepinephrine/Epinephrine (NE = potent vasoconstrictor; Epi = vasoconstricts at high doses, vasodilates at low doses via β2)
• Angiotensin II: potent vasoconstrictor
• Vasopressin (ADH): vasoconstricts at pharmacological levels
• Endothelin: most potent vasoconstrictor

Humoral Vasodilator Agents

• Bradykinin: dilates small arteries and arterioles
• Histamine: dilates arterioles, increases capillary permeability
• Prostaglandins: PGI2 (prostacyclin) = vasodilator; TXA2 = vasoconstrictor
• Nitric oxide (NO, EDRF): released by endothelium → potent vasodilator
• Serotonin: can cause vasoconstriction or vasodilation depending on context

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Chapter 18 - Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure

Vasomotor Center (in Medulla) ⭐⭐

1. Vasoconstrictor area (anterolateral upper medulla): sends sympathetic impulses via spinal cord → all arteries, arterioles, veins
2. Vasodilator area (anterolateral lower medulla): inhibits vasoconstrictor area → net vasodilation
3. Sensory area (nucleus tractus solitarius, NTS): receives input from baroreceptors (vagus + glossopharyngeal) → modulates vasoconstrictor/vasodilator areas

Sympathetic Vasoconstrictor Tone

• Vasomotor center fires continuously at 0.5-2 impulses/sec → maintains partial vasoconstriction (vasomotor tone)
• Blocking sympathetic tone (spinal anesthesia) → arterial pressure falls from 100 to ~50 mmHg
• NE release at vessel wall → α1 receptors → vasoconstriction

Baroreceptor Reflex ⭐⭐⭐

• Carotid sinus: more important in daily BP regulation (activated at ~60-180 mmHg)
• Aortic arch: also provides input

• Responds within seconds (fast!)
• Acts as a buffer - resists changes in BP (not a perfect regulator - resets with chronic hypertension)
• Most sensitive at normal arterial pressure range (~100 mmHg)

Chemoreceptor Reflex

• Central chemoreceptors: medulla (responds to CO2/H+)
• Peripheral chemoreceptors: carotid bodies (CN IX) and aortic bodies (CN X)
• Hypoxia/hypercapnia/acidosis → chemoreceptors → vasomotor center → vasoconstriction + increased BP

CNS Ischemic Response (Cushing Response)

• When brain blood flow is severely reduced → CO2 accumulates in brain → direct stimulation of vasomotor center
• Most powerful activator of vasomotor center
• Raises BP to very high levels to restore brain perfusion
• Only activated in extreme emergencies (e.g., ICP elevated near MAP)

Vasovagal Syncope

• Strong emotion/fear → cortex → hypothalamus → inhibits vasomotor center → massive vasodilation + bradycardia → BP drops → loss of consciousness

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Chapter 19 - Role of the Kidneys in Long-Term Control of Arterial Pressure and Hypertension

Pressure-Natriuresis Concept ⭐⭐⭐

Chronic vs. Acute Renal Output Curve

• The chronic renal output curve is much steeper than the acute curve
• This means: chronic changes in BP are much more powerful at regulating urine output
• Reason: chronic BP changes affect nervous and hormonal systems (reduces angiotensin II, aldosterone) in addition to direct hemodynamic effects

Long-Term BP Is Determined By:

1. Shift in renal output curve (kidney abnormality)
2. Level of salt/water intake

• Cannot change long-term BP without altering one or both!

Causes of Hypertension ⭐⭐

• Genetic factors, obesity, excess dietary salt, abnormal RAAS activity, sympathetic overactivity

• Renal artery stenosis → ↓ renal perfusion → ↑ renin → ↑ Angiotensin II → ↑ Aldosterone + vasoconstriction
• Primary aldosteronism (Conn's syndrome): excess aldosterone → Na+ retention
• Pheochromocytoma: adrenal medulla tumor → excess NE/Epi
• Coarctation of aorta
• Renal parenchymal disease: reduced ability to excrete Na+

RAAS System ⭐⭐

• Renin (from juxtaglomerular cells) → acts on Angiotensinogen → Angiotensin I
• ACE (lung) converts Ang I → Angiotensin II
• Angiotensin II actions: (1) vasoconstriction, (2) stimulates aldosterone, (3) promotes Na+ reabsorption at proximal tubule, (4) stimulates ADH release, (5) stimulates thirst
• Aldosterone (adrenal cortex): ↑ Na+ reabsorption + ↑ K+ secretion at collecting duct
• ACE inhibitors/ARBs → reduce Ang II → lower BP (and used in heart failure + diabetic nephropathy)

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Chapter 20 - Cardiac Output, Venous Return, and Their Regulation

Normal Values ⭐

• Cardiac output (CO): 5 L/min (at rest)
• Cardiac index: ~3.0 L/min/m² (normalized for body surface area)
• CO = Heart Rate × Stroke Volume = 72 × 70 ml = ~5 L/min

Primary Determinant of CO

• Tissues regulate their own blood flow based on metabolic needs
• CO = sum of all tissue blood flows

Cardiac Output Curves ⭐

• Normal plateau ≈ 13 L/min (2.5× normal)
• Hypereffective heart (sympathetic stimulation + hypertrophy): plateau ~25 L/min
• Hypoeffective heart (heart failure, ischemia, high afterload): reduced plateau

Venous Return Curves

• Mean systemic filling pressure (~7 mmHg): pressure when heart stops; the "driving pressure" for venous return
• Right atrial pressure (RAP) is the "back pressure" opposing venous return
• As RAP rises, venous return decreases (they intersect at cardiac output = venous return)

Combined Analysis (Guyton's Concept) ⭐⭐

• Plot CO curve and VR curve together
• Intersection = operating point of the cardiovascular system
• Sympathetic stimulation → shifts both curves right and up → increases CO

Factors Increasing CO

1. Decreased total peripheral resistance
2. Increased blood volume
3. Increased sympathetic tone (heart rate + contractility)
4. Exercise (most potent: can reach 25+ L/min in athletes)

Hypereffective Heart (↑ CO)

• Sympathetic stimulation
• Cardiac hypertrophy (athletes)
• Normal max output: 13-15 L/min; trained athlete: 25-30+ L/min

Hypoeffective Heart (↓ CO)

• Heart failure (systolic or diastolic)
• Valvular disease
• Coronary artery disease
• Myocarditis
• Anemia (output is normal but O2 delivery is reduced - compensation)

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Chapter 21 - Muscle Blood Flow and Cardiac Output During Exercise

Muscle Blood Flow During Exercise ⭐

• Resting skeletal muscle flow: ~3-4 ml/min/100g
• During heavy exercise: can increase 15-25x (to 50-80 ml/min/100g)
• Maximum muscle blood flow: ~20 L/min for the whole body
• Local vasodilation in active muscles mediated by: low O2, adenosine, CO2, K+, lactic acid, ATP

Why Arterial Pressure Rises During Exercise

• Sympathetic activation → vasoconstriction in non-exercising areas
• Increased HR + contractility
• Increased mean systemic filling pressure (venoconstriction)
• Net result: BP rises 20-80 mmHg during exercise
• Increased BP stretches vessel walls → additional vasodilation → muscle flow can increase 20x (more than what vasodilation alone could achieve)

Cardiac Output During Exercise

• Can increase from 5 L/min at rest to 25-30 L/min in trained athletes
• CO response to exercise: initial rapid increase due to sympathetic stimulation, then sustained by local vasodilation in muscles → ↓ TPR → ↓ right atrial back pressure → ↑ venous return → ↑ CO

Sympathetic Effects During Exercise ⭐

1. Vasoconstriction in inactive tissues (splanchnic, renal, skin - "fight or flight")
2. Brain and coronary arteries are spared (poor vasoconstrictor innervation - protective!)
3. Venoconstriction → ↑ mean systemic filling pressure → ↑ venous return

Cardiac Hypertrophy in Athletes

• Endurance athletes: volume-loaded hypertrophy (dilated cavities, thin walls - "athlete's heart")
• Strength athletes: pressure-loaded hypertrophy (thick walls, normal or small cavity)
• Marathon runners: heart mass increased 50-75%, CO plateau elevated 60-100%

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UNIT VII: RESPIRATION

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Chapter 38 - Pulmonary Ventilation

Lung Volumes and Capacities ⭐⭐

Mechanics of Breathing

• Diaphragm contracts → descends 1-7 cm → most important muscle of respiration
• External intercostals → elevate ribs → increase AP diameter
• Alveolar pressure falls to -1 cm H2O → air flows in

• Elastic recoil of lungs + chest wall
• Alveolar pressure rises to +1 cm H2O → air flows out
• Forced expiration: internal intercostals + abdominal muscles

Pleural Pressure

• Normally: -5 cm H2O at rest (sub-atmospheric; holds lung open)
• Falls to -7.5 cm H2O during inspiration
• This keeps alveoli open against elastic recoil

Compliance ⭐

• Normal total lung compliance = 200 ml / cm H2O
• Two components of elastic recoil forces:
  1. Lung tissue elasticity (elastin + collagen): ~1/3 of total
  2. Surface tension of alveolar fluid: ~2/3 of total

Surfactant ⭐⭐

• Secreted by Type II pneumocytes (alveolar cells)
• Chemical: dipalmitoyl phosphatidylcholine (DPPC)
• Reduces surface tension (especially at low lung volumes when alveoli are small)
• Follows Laplace's Law: P = 2T/r; without surfactant, small alveoli (smaller r) would have very high pressure → collapse
• Surfactant reduces T → prevents alveolar collapse (atelectasis)
• Neonatal Respiratory Distress Syndrome (NRDS/IRDS): premature babies lack surfactant → widespread atelectasis → treated with exogenous surfactant + CPAP

Dead Space

• Anatomical dead space: ~150 ml (conducting airways from nose to terminal bronchioles; no gas exchange)
• Physiological dead space = anatomical + alveolar dead space (poorly perfused alveoli)
• In normal lungs: physiological ≈ anatomical
• Alveolar ventilation = (TV - dead space) × RR = (500 - 150) × 12 = 4200 ml/min

Minute Ventilation vs. Alveolar Ventilation

• Minute ventilation: 500 × 12 = 6000 ml/min
• Alveolar ventilation (more important for gas exchange): ~4200 ml/min
• Deep breaths are more efficient than rapid shallow breaths!

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Chapter 39 - Pulmonary Circulation, Pulmonary Edema, and Pleural Fluid

Pulmonary Pressures ⭐

• Very low pressures vs. systemic circulation
• Normal pulmonary resistance = 1/7 of systemic resistance (very distensible vessels)

Hypoxic Pulmonary Vasoconstriction ⭐⭐

• Low alveolar O2 (PO2 <73 mmHg) → pulmonary vasoconstriction
• Mechanism: hypoxia → inhibits K+ channels in pulmonary vascular smooth muscle → membrane depolarization → Ca2+ influx → vasoconstriction; also ↑ endothelin, ↓ NO
• Purpose: diverts blood away from poorly ventilated alveoli to better-ventilated alveoli (V/Q matching)
• Systemic vessels DILATE in hypoxia (opposite) - sends more blood to low-O2 tissues

Distribution of Pulmonary Blood Flow (West Zones) ⭐⭐

• Zone 1 (apex): PA > Pa > Pv → capillaries may collapse (dead space) - usually absent in normal but occurs with severe hypotension or high PEEP
• Zone 2 (middle): Pa > PA > Pv → flow depends on Pa - PA
• Zone 3 (base): Pa > Pv > PA → flow dependent on Pa - Pv (most flow here)
• Blood flow at base > apex by ~10x in upright position

Pulmonary Edema ⭐

• Safety factor: pulmonary capillary pressure must rise from normal (~7 mmHg) to above plasma oncotic pressure (~28 mmHg) before edema occurs
• Left heart failure most common cause: ↑ left atrial pressure → ↑ pulmonary capillary pressure → edema
• ARDS (Acute Respiratory Distress Syndrome): damage to capillary membrane → increased permeability → edema even at normal pressures

Pleural Fluid

• Normally ~15 ml (thin lubricating layer)
• Pleural fluid moves by the same Starling forces as interstitial fluid
• Hydrothorax: increased pleural fluid (heart failure, hypoalbuminemia)
• Pneumothorax: air in pleural space → lung collapses

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Chapter 40 - Principles of Gas Exchange; Diffusion of O2 and CO2 Through the Respiratory Membrane

Partial Pressures ⭐⭐

• At sea level: atmospheric pressure = 760 mmHg
• Water vapor pressure at 37°C = 47 mmHg
• Dry atmospheric O2: 21% × 760 = 159 mmHg
• Humidified (in lungs): 21% × (760-47) = 149 mmHg
• Alveolar O2 (PaO2): ~104 mmHg (O2 absorbed continuously; CO2 added)
• Alveolar CO2 (PaCO2): ~40 mmHg
• Venous blood PO2: 40 mmHg; PCO2: 45 mmHg
• Arterial blood PO2: 95 mmHg; PCO2: 40 mmHg

Diffusion Through the Respiratory Membrane ⭐

• Thickness: 0.2-0.6 μm (extremely thin for rapid diffusion)
• Total surface area: 70 m² (about 40x the surface area of the body!)
• Diffusing capacity for O2: ~21 ml/min/mmHg at rest; increases 3x with exercise

• ΔP = pressure gradient
• A = cross-sectional area
• S = solubility
• d = distance
• MW = molecular weight

• O2 = 1.0
• CO2 = 20.3 (20x more diffusible than O2! Due to much higher solubility)
• CO = 0.81
• N2 = 0.53

Alveolar vs. Atmospheric Gas Composition

V/Q Ratio ⭐⭐

• Normal: ~0.8 (alveolar ventilation 4.2 L/min / cardiac output 5 L/min)
• High V/Q (deadspace-like, e.g., pulmonary embolism): well ventilated but poorly perfused → wasted ventilation
• Low V/Q (shunt-like, e.g., pneumonia, atelectasis): poorly ventilated but well perfused → wasted perfusion → hypoxemia (doesn't respond to supplemental O2 if true shunt)
• Main cause of hypoxemia in most clinical conditions

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Chapter 41 - Transport of O2 and CO2 in Blood and Tissue Fluids

Oxygen Transport ⭐⭐⭐

• Sigmoidal shape (due to cooperative binding)
• Normal Hb = 15 g/dl; O2 carrying capacity = 20 vol% (20 ml O2/100 ml blood)
• At PO2 95 mmHg (arterial): 97% saturation
• At PO2 40 mmHg (venous): 75% saturation
• Tissue extraction: 5 ml O2/100 ml blood per cardiac cycle

• Right shift (decreased O2 affinity, more O2 released to tissues): ↑ Temperature, ↑ CO2, ↑ H+ (↓pH = Bohr effect), ↑ 2,3-DPG
• Left shift (increased O2 affinity, O2 held tighter): ↓ Temperature, ↓ CO2, ↓ H+, ↓ 2,3-DPG, fetal Hb (HbF)

CO2 Transport ⭐⭐

1. Dissolved in plasma: 7%
2. As carbaminohemoglobin (CO2 bound to Hb): 23%
3. As bicarbonate (HCO3⁻): 70% - most important!

• HCO3⁻ exchanges out of RBC via chloride shift (Hamburger's shift)
• H+ is buffered by Hb

PO2 Values in Tissues

• Arterial blood: PO2 = 95 mmHg
• Interstitial fluid: PO2 = 40 mmHg
• Intracellular: PO2 = 23 mmHg (average in mitochondria; only ~1-3 mmHg needed for metabolism - large safety factor)

Carbon Monoxide Poisoning

• CO binds Hb with 240× greater affinity than O2 → carboxyhemoglobin (COHb)
• Displaces O2 from Hb + shifts curve left (O2 less readily released to tissues)
• Treatment: 100% O2 (or hyperbaric O2) - competitively displaces CO

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Chapter 42 - Regulation of Respiration

Respiratory Center (Medulla) ⭐⭐

1. Dorsal Respiratory Group (DRG) - medulla: primarily controls inspiration; generates the basic rhythm (inspiratory ramp signal)
2. Ventral Respiratory Group (VRG) - medulla: controls both inspiration and expiration; active during forced breathing
3. Pneumotaxic Center - upper pons: limits inspiration (turns off inspiratory ramp) → controls respiratory rate
4. Apneustic Center - lower pons: prolongs inspiration (counteracted by pneumotaxic center); if pneumotaxic center lesioned → prolonged gasping breaths = apneusis

How Respiratory Rhythm is Generated

• Inspiratory ramp signal: gradually increasing impulses to diaphragm/intercostals
• Abruptly switched off by pneumotaxic center or Hering-Breuer reflex → passive expiration
• Ramp restarts → next inspiration

Hering-Breuer Inflation Reflex

• Lung stretch receptors (in airways) → activated when TV > 3× normal (~1.5 L)
• Signals via vagus nerve → turns off inspiration
• Protective reflex against over-inflation (not important in quiet breathing)

Chemical Control of Respiration ⭐⭐⭐

• Located 0.2 mm beneath ventral surface of medulla
• Respond to H+ (primary stimulus) and indirectly to CO2
• CO2 crosses blood-brain barrier → reacts with H2O → H2CO3 → H+ → stimulates chemoreceptors
• H+ does NOT easily cross BBB → blood acidosis has less effect than blood CO2
• ↑ CO2 → ↑ H+ in CSF → ↑ ventilation (most important!)

• Carotid bodies (CN IX, at carotid bifurcation) - most important
• Aortic bodies (CN X)
• Respond to: ↓ O2 (PO2 < 60 mmHg, main trigger for O2 response), ↑ CO2, ↑ H+
• O2 response: minimal until PO2 falls below 60 mmHg (flat part of dissociation curve)
• In patients with chronic hypercapnia (COPD): "hypoxic drive" becomes dominant (CO2 receptors desensitized)

Effects on Ventilation ⭐

Exercise Hyperpnea

• Ventilation can increase 20× (to 100-150 L/min in heavy exercise)
• Mechanisms: (1) neurological stimulation from motor cortex; (2) joint/muscle proprioceptors; (3) ↑ CO2 + ↑ K+ in blood; (4) body temperature rise
• PaO2 and PaCO2 barely change during moderate exercise (ventilation matches production!)

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EXAM PREPARATION GUIDE

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HIGH-YIELD NUMBERS TO MEMORIZE ⭐⭐⭐

Cardiac

• Resting membrane potential (ventricular): -85 to -90 mV
• Action potential (ventricular): ~105 mV
• Conduction: 0.3-0.5 m/sec (atria/ventricle), 4 m/sec (Purkinje)
• Refractory period: ventricle 0.25-0.30 sec; atria 0.15 sec
• SA node rate: 60-100 bpm; AV node escape: 40-60 bpm; Purkinje escape: 15-40 bpm
• EDV: 120 ml; ESV: 40-50 ml; SV: 70 ml; EF: ~60%
• Normal CO: 5 L/min; Cardiac index: 3.0 L/min/m²
• Normal MAP: ~93 mmHg; BP: 120/80 mmHg

Circulatory

• Total plasma oncotic pressure: 28 mmHg
• Mean systemic filling pressure: 7 mmHg
• Capillary pressure: arterial end 35 mmHg, venous end 10 mmHg, functional mean 17 mmHg
• Glomerular capillary pressure: ~60 mmHg

Respiratory

• TLC: 5800 ml; VC: 4600 ml; TV: 500 ml; RV: 1200 ml; FRC: 2300 ml; Dead space: 150 ml
• Alveolar ventilation: ~4200 ml/min; Minute ventilation: 6000 ml/min
• Lung compliance: 200 ml/cm H2O
• Surface tension: 2/3 of total elastic recoil
• Alveolar PO2: 104 mmHg; PCO2: 40 mmHg
• Arterial PO2: 95 mmHg; PCO2: 40 mmHg
• Venous PO2: 40 mmHg; PCO2: 45 mmHg
• CO2 diffusion coefficient: 20× O2
• P50 = 26.5 mmHg; HbO2 saturation at rest: arterial 97%, venous 75%

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MOST COMMONLY TESTED CONCEPTS

"Classic" Exam Questions

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EXAM STRATEGY

What to Focus On First (High-yield for MCQ/SAQ exams)

1. Cardiac action potential phases - know each phase, ion responsible, unique features vs. skeletal muscle
2. Wiggers diagram - be able to label all events, explain a, c, v waves, heart sounds
3. Frank-Starling Law - mechanism, clinical relevance (heart failure, exercise)
4. Conduction system - pathway, velocities, intrinsic rates, autonomic effects
5. Starling forces (capillary fluid exchange) - normal values, causes of edema
6. Baroreceptor reflex - location, pathway, what it does
7. Pressure-natriuresis - why kidneys control long-term BP
8. RAAS - renin → angiotensin I → angiotensin II → aldosterone; effects
9. Lung volumes - all 8 values and which cannot be measured by spirometry (RV, FRC, TLC)
10. Surfactant - why it matters, who lacks it (premature babies), Laplace's Law
11. O2-Hb dissociation curve - shape, right vs. left shifts, P50, Bohr effect
12. CO2 transport - 3 forms (70% bicarbonate), Haldane effect
13. Chemical control of breathing - CO2 (central) vs. O2 (peripheral, kicks in < 60 mmHg)
14. V/Q mismatch vs. shunt - how to distinguish, why supplemental O2 doesn't help true shunts
15. Hypoxic pulmonary vasoconstriction - opposite of systemic, purpose = V/Q matching

For Long-Answer (Essay) Questions

• Always draw and label the Wiggers diagram when asked about cardiac cycle
• Draw the O2-Hb dissociation curve and mark shifts when asked about hypoxia or exercise
• For hypertension questions: always address the renal mechanism as the long-term regulator
• For heart failure questions: link Frank-Starling, CO curves, venous return, and compensatory mechanisms
• For respiratory failure questions: distinguish hypoxic vs. hypercapnic failure; mention V/Q ratio

Connections Between Chapters (Integration Questions)

• Exercise physiology (Ch. 21): integrates Ch. 9 (cardiac muscle), 17 (local control), 18 (sympathetic), 20 (CO regulation), 38 (ventilation), 41 (O2 transport)
• Heart failure: Ch. 9 (pump mechanics) + Ch. 15 (compliance) + Ch. 20 (CO/VR curves) + Ch. 19 (renal compensation)
• Hypertension: Ch. 18 (baroreceptors, short term) + Ch. 19 (kidneys, long term) + Ch. 17 (humoral factors)
• Pulmonary edema: Ch. 16 (Starling forces) + Ch. 39 (pulmonary circulation/pressures) + Ch. 19 (left heart failure)
• Altitude physiology: Ch. 38 (ventilation) + Ch. 40 (PO2 changes) + Ch. 41 (Hb curve adaptation) + Ch. 42 (hypoxic drive)

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