Chapter 17 - Cardiovascular System

Pulmonary Circuit - Oxygenate blood

Systemic Circuit - Oxygenate body/tissues

Arterial = away from heart, out of ventricles

Venous = towards heart, into atrium

Heart anatomy:

• Tissue layers:

  • Pericardium - outer covering, fibrous pericardium and parietal layer of pericardium

  • Epicardium (visceral pericardium) - inner serous membrane, secretes serous fluid into pericardium cavity

  • Myocardium - heart muscle

  • Endocardium - connective tissue/inner endothelium of heart

• Valves: open and close with pressure differences, segregate atria and ventricles (AV valves) and ventricles and arteries (semilunar valves)

  • Chordae tendineae - anchor AV leaflets to papillary muscles

  • Papillary muscles - contract to hold valve closed and prevent backflow from ventricular contraction

    • insufficiency - valves weak and allow back flow (forces heart to work harder)

    • stenosis - valves stiffened and misshapen, creates turbulent flow leading to blood clots/strokes, may also need extra pressure/effort to open (strain)

• Sounds: “lub-dub” = AV and then semilunar valves closing, murmur caused by stenosis or insufficiency

• Coronary circulation - branches off aorta and returns to right atrium (through coronary sinus)

  • circulation needed because the tissues are too thick in the heart to rely on diffusion from the chambers alone (extend into myocardium)

• Cardiac Muscle

  • Similarities: striated myofibril/sarcomere structure, T-tubules to carry AP to SR, troponin based excitation-contraction coupling

  • Differences: no fascicle structure, gap junctions, pacemaker, Ca⁺² from outside of cell, can be excited or inhibited by ANS

  • Unique: branched and y-shaped cells, myofibrils irregularly aligned, strictly aerobic respiration

  • Intercalated discs - gap junctions and desmosomes anchoring neighboring cardiac cells to allow direct AP conduction, behaves as a single coordinated pump

Action Potential

• Pacemaker cell - generate depolarization to trigger AP (SA node, AV node/bundle, Purkinje fibers)

  • Automaticity - heart beats on its own, rhythmically

  • Pacemaker potential is an unstable, rising “resting” potential due to Na⁺ entering via F-type sodium channels (open at -60mV, driven by K⁺, ‘hyperpolarized’) to progressively depolarize to threshold. Main polarization is from T-type (fast) Ca⁺² channels (open around -50mV) which then accelerate pacemaker to L-type (slow Ca⁺²) threshold of -40mV. K⁺ restores membrane to -60mV

• Conducting cells - carry AP quickly from nodes throughout heart, internodal pathway (bundle of His/bundle branches, purkinje fibers)

• AP propagation: (1) Sinoatrial (SA) node generates impulse, (2) Depolarization spreads via gap junctions to atrioventricular (AV) node, delayed by 0.1 seconds, atria contract before ventricles, (3) pulse sweeps to AV bundle (only thing that connects atria and ventricles), (4) bundle branches conduct impulse through intraventricular septum to apex, (5) subendocardial conducting network (purkinje fibers) excite ventricles and they contract from the bottom up

  • SA node = 100 bmp intrinsic, ~70 bpm with vagal tone (parasympathetic “break”)

    • sets normal HR (fastest)

  • AV node = 50 bpm (backup pacemaker for isolated ventricular contraction)

    • impulses from SA reach AV before it would reach threshold on its own, AV responds to external stimulation under normal conditions (also a backup)

  • P fibers = 30 bpm (rescue pacemaker if bundles are blocked)

• Ions: slow L-type Ca⁺²channels maintained a longer depolarized state (200+ ms) to ensure ventricle can contract to reach proper end-systolic volume and AP is as long as the twitch so the heart cannot tetanus (contract without relaxing). This also sets the maximum heart rate around 220 bpm

  • L-type stays open past the K⁺ channels to maintain depolarization; eventually they close and K⁺ can restore potential

• Innervation:

  • SyANS - increase HR through beta-adrenergic receptors by depolarizing pacemaker faster, increase Ca⁺² concentration and EC coupling

  • PaANS - decrese HR through inhibitiory muscarinic cholinergic receptors, hyperpolarizing pacemaker to slow threshold

• EKG - medical tool to evaluate heart function based on electrical impulses/timing

  • P-wave - atrial contraction

  • QRS complex - atrial relaxation and ventricular contraction

  • T wave - ventricular relaxation

• Cardiac cycle - volume, pressure, electrical changes and EKG, valve actions, sounds

  • Systole - begins at ventricular contraction, isovolumetric as pressure builds in contracting ventricle; V pressure rises above A pressure and AV valve closes (first heart sound and QRS complex, ventricle contains EDV). V pressure above arterial pressure and semilunar valves open (ventricular ejection, ejection fraction of ventricular blood flows into arteries)

  • Diastole - begins at ventricular relaxation (T wave), isovolumetric as pressure drops below arteries and semilunar valves close (second sound), ventricle contains ESV. Relaxation continues and blood flows into atria, pressure exceeds ventricular and AV valves open allowing blood into ventricle (80% passive filling dues to pressure gradient). P-wave occurs and atrium contracts to force remaining 20% into ventricle. Atrium relaxes and another QRS complex begins, reenters systolic, cycle continues.

• Right vs Left - Pressures in LEFT are greater because the length and resistance of the systemic circuit are greater; left has much more muscle to generate 4x the pressure to move blood (same ventricular capacities)

Diseases

• tachycardia - high resting heart rate (over 100)

• bradycardia - low resting heart rate; different for athletes (under 40 dangerous)

• arrhythmia - failure of coordinated heart rhythm

  • ectopic focus/extrasystole - competing pacemaker signal (with SA)

  • premature contractions (PAC or PVC) - an early beat followed by normal with more force than usual

  • bundle block - AV node or bundle of His are not functioning properly (ventricles fall behind)

  • pulmonary arrhythmia - normal reflex to change HR based on changing thoracic pressure

  • fibrillation - lack of coordination and ineffective blood pumping

    • more worrisome in ventricles bc they cannot pump blood

  • coronary atherosclerosis - buildup of plaque that occludes lumen and limits blood flow (dangerous in small coronary vessels and can cause heart attack)

  • high blood pressure (150/90) - blood volume mis-management, diastolic number more important

    • beta blockers - reduce sympathetic tone from epinephrine

    • ACE inhibitors - block enzymes for ANGII

    • ARBs - block ANGII receptors

    • CCbs - Ca⁺² channel blockers

  • myocardial infarction - denial of blood to heart (heart muscles will be damaged and/or die), heart attack

  • cardiomyopathy - enlargement of heart (ventricles), weakened and flabby ventricles that cannot pump blood effectively

    • if afterload is too high it will not be able to compensate and leads to heart failure

  • congestive heart failure - high systemic afterload and excessive ventricular effort results in damage or disfunction and heart too weak to attain effective ESV

    • sometimes body compensates early on with kidneys and blood volume

    • left-sided because of the higher pressure (leads to buildup of fluid in lungs due to leakage from pulmonary circuit)

Chapter 18 - Circulatory System

Blood vessels:

• Elastic arteries - high pressure, high flow, low resistance, high elasticity (propel blood by expanding and passively contracting with pulses to maintain blood pressure), upper arterial tract

• muscular arteries - high pressure, high flow, low resistance, lower elasticity and more muscular activity to modify flow to organs

• arterioles - lower pressure, lower flow, higher resistance (high tuning), highest pressure drop (resistance vessels); maintain total peripheral resistance (TPR) and BP by smooth muscle action and small lumen (sympathetic tone controlled)

• capillaries - low pressure, low flow, high surface area; filters for blood into (filtration) and out of (reabsorption) the interstitial fluid; diffusion/transport of gases, waste, nutrients, signaling molecules

  • continuous - strong barrier, pinocytosis fluid movement, most common, forms blood-brain barrier (some intercellular clefts for filtration)

  • fenestrated - porous barrier, stops most proteins but high bulk fluid movement through fenestrations/clefts, areas of high filtration/reabsorption (kidney, digestive, endocrine)

  • sinusoid - very porous, allows unrestricted fluid flow through sinunsoids (proteins and cells), bone marrow, liver, adrenal medulla

• venules (little veins) - transition structure between capillaries and veins, some functional aspects in reabsorption

• veins - low pressure, high flow (low flow RATE), high compliance (low elasticity); low pressure gradient BUT check valves and muscle/respiration-based pumping moves blood to heart, volume reservoir (activity forces blood into circulatory flow to deliver gases/nutrients quicker)

Flow

• Systemic - 75% (60% in venules alone, blood reservoir)

  • Arterial flow at rest: 20% muscles, 25% abdominopelvic organs, 13% brain, 20% kidney

• Pulmonary - 12% (5% in capillaries, 8% in heart)

• Cardiac output (CO) = stroke volume x BPM

  • CO of systemic and pulmonary are the same, stroke volume is equal and beats are coordinated

• Preload - pressure on resting heart from venous return, (left-ventricular end diastolic pressure, LVEDP) leading to stretch on heart

  • Frank-Starling relationship - increased preload → increased contraction (resting cardiac muscle is shorter than optimal, so when stretched it can provide a larger contraction)

• Contractility - strength of contractions at given stretch (controlled extrinsically by SyANS and endocrine system)

• Afterload - amount of diastolic pressure on heart by arteries (backpressure against ventricular contraction)

  • increased by high BP, arteriosclerosis, atherosclerosis/stenosis

  • heart is adapted to normal pressure, but increased P can cause valve damage (elevated diastolic pressure is more concerning to doctors!)

• SV = EDV - ESV

  • End diastolic volume (EDV) - highest volume of ventricle during cardiac cycle, determined by venous return (but mostly physical activity or SyANS activity)

  • End systolic volume (ESV) - lowest volume of ventricle during cycle, function of how hard the ventricle is working (contractility) and afterload; altered by SyANS, endocrine and humoral

• Flow = difference in pressure / resistance

  • arterioles have greatest resistance and also easiest to control resistance (diameter) and therefore flow (also manages MAP upstream)

  • HR and SV changes are not to change MAP but rather provide the flow required (TPR is the main SHORT TERM way to change MAP)

• MAP = diastolic pressure + 1/3 pulse pressure

  • systolic - pressure at peak of ventricular contraction

  • diastolic - pressure when ventricles are relaxed and filling

  • pulse pressure - difference between systolic and diastolic

  • MAP proportional to CO and TPR; changes in HR, SV, CO, vascular tone ALL affect pressure (long-term changes in volume are done by kidney)

• Autoregulation - intrinsic control at the tissue level, responds to local nutrient/waste levels, loss of blood flow, skeletal muscle activity, temperature

  • dilation of local vessels to increase flow to metabolically needy tissues

• Active hyperemia - blood flow increases (vasodilation) to muscles when active due to decrease in nutrients and O2 and increase in temperature

• Filtration and Reabsorption

  • 20 L/day filtered out of plasma into ISF from arteries and 17 L/day is reabsorbed into plasma on venous side

    • 3 L/day remains in ISF and becomes lymph (unless swelling is occurring); returned to circulation, through lymphatic drainage into subclavian artery

  • starling forces (hydrostatic [bulk] and osmotic [solute])

    • hydrostatic pressure - force on wall from fluid

      • capillary HP - filtration through capillary walls (35 mmHg)

      • interstitial fluid HP - reabsorption through capillaries (17 mmHg)

    • colloid osmotic pressure - force opposing HP, large non-diffusible molecules

      • capillary OP - plasma proteins in blood (25 mmHg ISF to blood)

      • interstitial fluid OP - (0.1-5 mmHg)

    • fluid flows out of capillaries at the start (net +10) and back into capillaries at the end (net -8)

Neurological control

• vasomotor tone - constant stimulation by SyANS through maintenance norepinephrine and epinephrine produced by the adrenal medulla (a bit constricted at rest, BP drops at night when SyANS is slowed, high BP is a sign of stress)

• baroreceptors - located in carotid sinus and aortic arch to measure BP and report to medullary cardiovascular center

  • increased pressure → increased Action Potential frequency → increased CV efferent signals → increase SyANS activity → increase HR and SV

  • only respond to changes in “normal” so it will not affect high resting BP (tolerance)

• chemoreceptors - present in carotid sinus and aortic arch (measure pH and O₂ levels and brain stem (osmolarity)

  • changes in gas concentration → increased activity of cardioacceleratory center → regulation of breathing

Endocrine controls

• epinephrine - SyANS, accelerates HR, increases SV, increases vasoconstriction, increases BP

  • mainly to maintain MAP with external conditions and activities

• angiotensin II/III - renin-angiotensin-aldosterone system (RAAS)

  • ANGT to [by renin] ANGI to [by ACE] ANGII to [by ACE2] ANGIII;

  • ANGII stimulates aldosterone, causes vasoconstriction when BP low;

  • ANGIII stimulates aldosterone but NOT vasoconstriction

    • response to low BP or volume, ACE inhibitors are effective anti-hypertensive drugs

• vasopressin/ADH - posterior pituitary to affect low BP and/or high osmotic strength

  • long-term (renal) to reabsorb more water into bloodstream

  • ONLY way to alter osmotic problems other than thirst (does not move salt)

  • at high levels it is also a vasoconstrictor, short-term, in conjunction with ANGT (angiotensin)

• Long term control: RAAS and kidney

  • aldosterone - water/mineral balance in body (mineralocorticoid); increases water retention in kidneys by reabsorbing sodium, increases K⁺ excretion by kidney (high potassium, low sodium, low BP, SyANS and RAAS stimulate aldosterone)

  • atrial natriuretic peptide (ANP) - produced by heart, stimulated by myocardial stretch in atrium; antagonizes aldosterone and decreases ADH production, generalized vasodilation through renin inhibition

  • vasopressin/ADH

  • EPO - produced by kidney in response to low P_O2, increases RBC production and oxygen transport capacity

    • high altitude is a huge trigger here (Olympic training center in CO spgs)

    • will increase blood viscosity and thus BP/resistance, however most systems balance this out

Diseases

• Hypertension - high blood pressure (over 130/90)

  • risk factors: genetics, stress, obesity/diet, age, smoking

  • treatments: lifestyle changes (diet, exercise), lowpressors (ACEi, beta-blockers) as vasodilators, diuretics (Lasix) to lower blood volume

• Hypotension - not common, but shock is life-threatening (lack of adequate blood flow, 90/60)

  • hypovolemic - low blood volume (hemorage)

  • vascular shock - poor circulation due to vasodilation

    • anaphylactic - widespread vasodilation due to histamine cascade (allergy)

    • neurogenic - ANS disruption (psychological or “fear” shock)

    • septic - widespread infection (vasodilation) or DIC (clotting that blocks blood flow)

  • cardiogenic - heart problems and cannot sustain BP (heart attack or failure)

Chapter 21 - Respiratory system

Ventilation and Pressures

• Ventilation = breathing, exchanging air outside the body with air inside lungs

  • driven by muscle contraction (diaphragm and intercostal muscles) that create pressure differences (works due to vacuum seal of pleural membranes)

  • intrapleural negative pressure (seal) changes pressure on lung wall and thus lung volume

  • Inhalation - contraction of diaphragm (lowers) and external intercostals (raises)

    • forced inhalation - engages inspiratory reserve volume (use of scalenes)

  • Exhalation - relaxation of diaphragm (raises) and contraction of internal intercostals (lowers)

    • forced expiration - engages expiratory reserve volume (use of abdominals)

• Boyle’s Law: P₁V₁ = P₂V₂

• F = DP/R (DP= difference between atm and lung pressure, R determined by radius of bronchi)

Characteristics of respiration

• compliance - extent of stretchiness (measured in DV/DP)

  • determined by health of tissue and alveolar surface tension

    • lung surfactant - biological detergent to disrupt surface tension in alveoli which would otherwise exert so much force that the lung collapses (keeps them open)

• anatomical dead space - amount of air in conducting airways that cannot undergo gas exchange (150/500 mL is dead space)

• alveolar dead space - alveoli that get air but not effective blood flow to exchange gases

  • V/Q balancing eliminates airflow to these alveoli

Respiration

• Respiration = gas exchange between air and blood or blood and tissues (requires dissolution and diffusion)

  • dissolution - amount of CO2 and O2 in the blood, measured as partial pressures

  • Dalton’s law = sum of partial pressures = atm pressure

  • Henry’s law = gas dissolved in liquid related to P_gas

• Pressure gradient - drive diffusion

• Thickness (permeability) and surface area - greater SA = faster diffusion (40x SA of skin)

• Gas solubilities - O2 is faster but CO2 is more soluble

• V/Q coupling - control of each variable to balance air and blood flow (~0.8, not 1 due to gravity)

  • V=alveolar ventilation rate (AVR)

    • change in ventilation → change in perfusion (controlled by P_O2)

  • Q=perfusion (cardiac output, CO)

    • change in perfusion → change in ventilation (controlled by P_CO2)

• internal respiration - tissue exchange of gasses with bloodstream (systemic capillaries)

• Oxygen transport

  • 1.5% dissolved in plasma (100 mmHg in arterial blood, 40 mmHg in venous)

  • 98.5% bound to hemoglobin (4 O₂/molecule, 98% saturated at 100 mmHg)

    • 25% unloaded at rest

    • 80% unloaded under metabolic demand (decreased O2 and increased CO2/decreased pH)

      • Bohr effect decreases O2 affinity with decreasing pH

• CO₂ transport

  • 10% dissolved in plasma

  • 70% converted to HCO3 (bicarbonate buffer system)

    • partial pressures do not change as much as O2 due to the buffer system

  • 20% bound to hemoglobin as carbamate (bound to amino group)

    • Haldane effect decreases how much CO2 can bind when higher O2 binding

Innervation

• Medulla and pons - three centers to control unconscious breathing

  • ventral respiratory group (VRG) - contractile stimuli to inspiratory and expiratory muscles in an oscillating pattern

    • pre-Botzinger complex = first respiratory pacemaker discovered

  • dorsal respiratory group (DRG) - integration of chemoreceptors and stretch receptors to modulate VRG

  • pontine respiratory group (PRG) - smooths out transitions and also voluntary activities (deep breathing and vocalization)

• hypothalamus - integrates strong emotion and pain to respiratory responses

• cerebral cortex - voluntary control over respiration (hold breath)

  • can be overridden when CO2 accumulates

• hering-breuer reflex - stretch receptors to prevent over-inflation of lungs

Diseases

• atelectasis (collapsed lung)- damage to lung tissue or chest wall has broken vacuum seal of pleurae so there is no pressure gradient; air in thorax means no breathing (shrinks like balloon)

• pneumothorax - air in pleural cavity, no pressure gradient, pulled out with tubes

• Infant Respiratory distress syndrome (IRDS) - babies don’t produce enough surfactant and have trouble inflating alveoli

• fibrosis - damage/scarring of lung tissue stiffens wall and reduces compliance

• asthma - brachioconstriction limits airflow significantly

• pneumonia - fluid accumulated in alveoli, preventing air from entering respiratory spaces

• hypoxia - lack of oxygen in the tissues of the body (must drop below 60% in plasma before it becomes a major respiratory drive)

  • anemic - not enough RBC or Hb

  • ischemic - blockage in blood flow (heart attack)

  • histotoxic - body can’t use oxygen even if it’s available (cyanide)

  • hypoxemic - respiratory distress

  • CO poisoning - competitive inhibitor of O2 binding to Hb

• hypercapnia - excessive CO2 in blood

  • chemoreceptor reflexes are sensitive to CO2 and alter ventilation to compensate (O2 sensors are less sensitive, mainly backup for CO2 sensors)

• hyperventilation - CO2 exchange > CO2 metabolism

  • excessive ventilation, O2 affinity increases (not released) and it is not released when needed

• hypoventilation - CO2 exchange < CO2 metabolism

  • not enough ventilation, blood is acidic, will also result in low O2

• Chronic Obstructive Pulmonary Disease (COPD) - irreversible decrease in ability to force air out of lungs

  • emphysema - destruction of alveolar walls, loss of elasticity, increase in compliance, loss of effective respiration (leads to increased strain on right side of heard)

  • chronic bronchitis - inflammation, mucus, narrow bronchi (resistance to outflow of air, leading to hypoventilation causing an oxygen-dependent respiratory drive

• Altitude sickness

  • body overreacts to changes in O2, fatigue, shortness of breath, nausea, headache (over 8000 ft)

  • Acclimation is possible over time

    • low P_O2 in air → low P_O2 in blood → increased O2 and CO2 chemoreceptors → stimulation respiration, BPG increases and more O2 is released by Hb

    • low O2 in kidney stimulates EPO to produce more RBC (compensate for low P_O2)

• SARS-CoV-2

  • spike proteins bind to ACE2 and enters the cell (prominent in heart and lung tissues)

    • not the mechanism for damage, simply the key into the cell; explains the localization in these tissues

  • infection-driven inflammation and immune activities → damaging interstitial pneumonia