PHYS 5024 Week 6 Notes Schmidt PDF

PHYS 5024 Week 6 Notes Schmidt Medical Physiology: Principles for Clinical Medicine, by Rodney A. Rhoades and David R. Bell, Chapters 16, 18 & 19 Reminder: watch the narrated PowerPoint presentation on Spirometry before your week 6 spirometry lab session. Spirometry...

PHYS 5024 Week 6 Notes Schmidt Medical Physiology: Principles for Clinical Medicine, by Rodney A. Rhoades and David R. Bell, Chapters 16, 18 & 19 Reminder: watch the narrated PowerPoint presentation on Spirometry before your week 6 spirometry lab session. Spirometry -tidal volume (VT): volume of air leaving the lungs during a breath (typically about 500 ml) -total lung capacity: maximum air volume in lungs at maximal inhalation (about 6 L) -functional residual capacity (FRC): air remaining in lungs at the end of expiration during a normal breath; two parts..... *expiratory reserve volume (ERV): additional air that can be forced out of the lungs by forced expiration *residual volume (RV): additional that cannot be forced out by forced expiration -inspiratory reserve volume (IRV): maximum additional volume of air that can be inhaled beyond the tidal volume -vital capacity (VC): IRV + VT + ERV *a measure of VC is the forced vital capacity (FVC): the subject inspires maximally then rapidly exhales as completely as possible. *FEV1 (forced expiratory volume): the volume exhaled in the first second, typically about 80% of total FVC *FEF25-75: air flow rate (L/sec) when from 25% to 75% of the FVC volume is measured *These measures of lung capacity are reduced (with high residual volumes) by conditions such as: -bronchitis (inflammation, excessive mucus plugging small airways) -emphysema (loss of normal lung elasticity, airway collapse) -asthma (bronchial smooth muscle contractions, airway constriction) *chronic obstructive pulmonary diseases (COPD) can result in: -hypoxemia (low blood oxygen) -hypercapnia (high blood carbon dioxide) - hypoxia-induced increase in pulmonary vascular resistance (next week) -estimation of residual volume (RV): *test subject performs a forced expiration then *breaths 10% helium from a source with fixed volume *the helium will be diluted with the non-helium containing air in the residual volume *the decreased helium concentration reflects the size of the residual volume -restrictive lung disorders (interstitial lung disease) *total lung capacity reduced * FEV1/FEV can be increased Special Circulations cardiac circulation -coronary blood flow reserve: blood flow to the heart can increase about 4-5 fold during exercise *very little capacity for glycolysis; oxygen demand must be met *metabolic products such as adenosine act as local vasodilators *NO from endothelial cells also supports vasodilation -reduced coronary blood flow during systole *due to compression of small coronary blood vessels *complicates heart disease *coronary vascular disease -collateral vessels: allows some adaptation for artery blockage -relationship between cardiac output and oxygen use *stroke work: work done by the heart in moving blood can be estimated as SW = SV x MAP SV=stroke volume MAP=mean arterial pressure *stroke work is only 5-20% of the total energy needs of the heart -example: during isovolumetric contraction large amounts of energy is consumed but there is no work done moving blood *almost all heart energy comes from oxidative metabolism, so total energy demand closely corresponds to the rate of oxygen use *changes in energy demand and blood flow can be estimated as the product of the heart rate and the arterial pressure cerebral circulation -good autoregulation of blood flow at blood pressures from 55-155 mm Hg *CO2 and K+ trigger dilation of blood vessels *involves NO from neurons and endothelial cells small intestine circulation - during digestion, blood flow increases in proportion to metabolic demand - the vasodilators adenosine and NO are released during absorption of nutrients - sympathetic stimulation of vasoconstriction greatly reduces blood flow and nutrient absorption during exercise hepatic circulation - both an arterial blood supply and the hepatic portal vein *blood from both sources mixes in the capillaries *local control of arterial blood flow (reciprocal matching) in response to changes in portal blood flow -capillaries endothelial cells have gaps; very leaky -liver vasoconstriction following sympathetic stimulation can shift a significant volume of blood out of the liver skeletal muscle circulation -blood flow can increase about 20 fold in response to exercise -some vasodilation due to beta adrenergic receptors, but most is in response to local metabolic demand (autoregulation) -vasoconstriction is possible in response to blood loss and baroreceptor response to activate sympathetic stimulation dermal circulation -specialized for temperature regulation *in warm climates, increased blood flow allows heat to be lost from the body -arteriovenous anastomoses; hands, feet, parts of the head *in hands and feet, reduced adrenergic stimulation results in vasodilation *other regions of skin has cholinergic sympathetic nerves that mediate both sweating and an active vasodilation, "cutaneous active vasodilator system" *Rhoades says active vasodilation involves the vasodilator bradykinin, but this might not be the case "In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges" http://jap.physiology.org/cgi/content/full/100/5/1709 *blood vessels also dilate when skin is warmed *in cold, adrenergic sympathetic nerves cause vasoconstriction that limits blood flow to the skin to minimize heat loss -if skin gets too cold, vessels eventually dilate and blood flow protects skin from damage Lung Ventilation Respiration: oxygen to tissues and carbon dioxide removed from tissues - gas exchange: dynamic range of about 20x * pulmonary capillaries: atmosphere - blood exchange * systemic capillaries: blood - tissue exchange - cellular respiration *metabolic reactions that produce carbon dioxide *oxygen use as electron acceptor for oxidative phosphorylation respiratory system structure and function -needed: a large surface area for gas exchange between air and blood -made possible by highly branching vascular and airway trees -conducting zone of airway tree *branching bronchi and bronchioles and terminal bronchioles *initial branches with cartilage support against collapse  *smaller branches supported by elasticity of lung tissue *the bronchial circulation originates from the descending aorta -not involved in gas exchange while passing through the conducting zone *air is warmed and humidified *dust and bacteria removed -ciliated epithelium pushes mucus and debris to the pharynx - respiratory zone of airway tree * respiratory bronchioles with some attached alveoli * termini: alveolar ducts between dense collections of alveoli *ventilation function: movement of fresh air into and out of alveoli *alveolar surface area is about 75 m2 *alveoli are closely associated with the pulmonary circulation -70-80% of the alveolar surface is covered by capillaries *oxygen and carbon dioxide diffuse between the capillaries and the alveoli -distance is as small as 0.5 m *blood flow through pulmonary capillaries is relatively fast -typically several fold faster that in systemic capillaries Breathing: pressure changes and air flows -contraction of the diaphragm expands the volume of the thoracic cavity *normal breath: 1-2 cm movement of the diaphragm *deep breath (forced inspiration): movement as large as 10-12 cm -rib muscles can contribute to expanded volume of the thoracic cavity -abdominal wall expiratory muscles contract during forced expiration *this forces the relaxed diaphragm further into the thoracic cavity -relationship between thoracic cavity volume and lung volume *increased thoracic cavity volume reduces pressure in the pleural space - pleural space contains fluid between the lungs and the chest wall - pleural space pressure is slightly below atmospheric pressure except during forced expiration -negative pleural space pressure is generated by tension from the lungs and the chest wall both pulling away from the pleural space *the lungs expand against the reduced pressure in the pleural space -transpulmonary pressure: alveolar pressure minus the pleural space pressure *increased transpulmonary pressure when the lungs are inflating -transairway pressure: airway pressure minus the pleural space pressure * during forced expiration pleural space pressure becomes positive, airway pressure also goes higher limiting airway collapse Gas pressures *typical atmospheric pressure is about 760 mm Hg  -also called barometric pressure *the total pressure of a mixed gas is the sum of the individual partial pressures *the partial pressure of oxygen in dry air is (760 x 0.21) = 160 mm Hg = PO2 - 21% of air is oxygen *in the humidified and warm air in lungs PH2O = 47 mm Hg *air pressure gradients that move air into and out of lungs are small *these pressures are often expressed as cm H2O - 1 mm Hg = 1.36 cm H2O *inspiration: alveolar pressure -2 cm H2O relative to atmospheric pressure *expiration: alveolar pressure +3 cm H2O relative to atmospheric pressure pneumothorax *lung or chest wall puncture allows air to enter the pleural space *pleural space attains atmospheric pressure *the lung will collapse *the mediastinal membrane restricts the collapse to one lung Pressure changes during the breathing cycle -inspiration *at start: -respiratory muscles are relaxed -alveolar pressure is zero (atmospheric pressure) -air flow is zero - pleural space pressure = -5 cm H2O - transpulmonary pressure = 5 (distending pressure keeping lungs inflated) *diaphragm contraction reduces pleural pressure towards -8 cm H2O -as transpulmonary pressure increases the lungs inflate -alveolar pressure becomes negative -air moves into the lungs according to the mouth-alveolar pressure gradient *at end alveolar pressure equals atmospheric pressure and air flow stops -expiration *the diaphragm relaxes and pleural pressure increases (less negative) *as transpulmonary pressure decreases the lungs deflate *alveolar volume decreases and pressure increases above atmospheric pressure *air flows out of the lungs until alveolar pressure equals atmospheric pressure *resistance to air flow is greater during expiration -alveolar pressure increase greater than the decrease during inspiration -expiration lasts slightly longer than inspiration Alveolar ventilation (VA) L/min - dead space volume (VD): *with a 500 ml inhaled breath about 150 ml is in the conducting airways  -anatomic dead space volume *there can also be alveolar air that does not participate in gas exchange -for example, due to poor capillary supply to alveoli -alveolar dead space volume -physiological dead space volume = anatomic + alveolar dead space volumes - VA = (VT - VD) x f volume of fresh air reaching functioning alveoli per minute * f = breaths per minute - increased rate of breathing (f) is not very effective for increasing VA if VT decreases * dead volume becomes a larger fraction of VT - increased depth of breathing is more effective for increasing VA * dead volume becomes a smaller fraction of inspired air - a high rate of alveolar ventilation helps remove carbon dioxide from the body and deliver oxygen (next week, gas transfer) mechanical properties of the lungs -elasticity of the lungs is important for their easy of expansion when transpulmonary pressure increases and their return (recoil) to resting size when transpulmonary pressure decreases -distensibilty: the ease with which lungs inflate *distensibility and recoil are inversely related *if lungs are too easy to inflate then there will not be much elastic recoil *lung elasticity depends on matrix proteins like elastin -lung compliance *the change in lung volume (V) corresponding to a change in pleural pressure (P) * V / P = lung compliance * lung compliance is smaller at higher lung filling volumes * restrictive lung disease causes low compliance and low distensibility *more muscle work required (lower pleural pressure) to get normal lung inflation *in the obstructive disorder emphysema *elasticity is lost and there is high compliance (easy to inflate) *but little elastic recoil and there is usually a large residual air volume -chest wall elasticity *at about 70% of maximum lung capacity chest wall recoil is zero *below 70% chest wall recoil is directed outward -outward recoil is maximal at the lung residual volume *above 70% of maximum lung capacity chest wall recoil is directed inward -inward recoil is maximal at total lung capacity surface tension - surface tension of water is a force arising from the preference of water molecules for each other rather than for air, this force resists lung inflation - surface tension at the lung surface area acts as an elastic force in parallel with lung tissue  -the elastic force due to surface tension is about two thirds of the total -surface tension makes the lung significantly less compliant (less distensible) -pulmonary surfactant *reduces the alveolar surface tension *produced by Type II alveolar cells *surfactant contains phospholipid that spreads over the air-water interface -dipalmitoylphosphatidylcholine (DPPC) *premature babies have too little surfactant, higher surface tension and difficulty keeping alveoli inflated (infant respiratory distress syndrome) airway resistance - due to either turbulent air flow during high rates of air movement in the large airways or laminar flow - air flow (V) is *proportional to the pressure difference driving flow (mouth to alveoli, Pmouth – PA) *inversely proportional to the resistance (airway resistance, Raw) * V = (Pmouth – PA)/Raw * Raw = (Pmouth – PA)/ V - airway resistance is fairly constant during normal breathing (at rest) *not constant during vigorous exercise and forced expiration *when lung volume is reduced (in association with forced expiration) resistance is high due to compression of airways *during forced expiration pleural pressure can be 30 cm H2O -the high pleural pressure can cause airway constriction -regulation of airway resistance *bronchial constriction -parasympathetic stimulation (mAChR, release of intracellular Ca++) -local factors such as histamine (from mast cells during allergy) *bronchial dilation -circulating epinephrine acting on 2 receptors -high airway carbon dioxide work of breathing - at rest the energy for breathing might be 5% of total energy demand - during exercise breathing might account for 20% of total energy demand - in restrictive lung disease, greater work is required to produce a normal tidal volume *to minimize this work, breaths tend to be rapid and shallow - in obstructive lung disease, patients tend to take deeper breaths than normal *this is a way of reducing lung resistance * greater energy is expended due to the higher resistance Gas exchange between alveolar air and pulmonary capillaries -Differences in oxygen concentrations between the atmosphere and alveoli: -in the humidified and warm air in lungs PH2O = 47 mm Hg (saturation at body temperature) *increased water vapor of inspired air dilutes the oxygen from 160 to 150 mm Hg -mixing inspired air with air in the functional reserve capacity * the functional reserve capacity is about 2.3 liters * less than 0.5 L of fresh air reaches the alveoli with each breath (at rest) *the fresh air is diluted with existing old air in the lungs, giving a typical alveolar partial pressure of oxygen of about 102 mm Hg -net diffusion of oxygen and carbon dioxide *depends on concentration differences, net diffusion from high to low concentration *concentrations of gases are proportional to their partial pressures *diffusion of oxygen from air in alveoli to blood -typical partial pressure of oxygen in alveoli: 102 mm Hg -typical partial pressure of oxygen in pulmonary artery blood: 40 mm Hg -at rest, net oxygen diffusion into blood is complete before blood exits the capillaries *a greater amount of oxygen transfer to blood is possible if capillary blood flow increases *during exercise capillary blood flow increases, but oxygen diffusion is still fast enough so that the alveolar and blood partial pressures of oxygen have time to equilibrate *diffusion of carbon dioxide from blood to air in alveoli -typical partial pressure of carbon dioxide in alveoli: 40 mm Hg -typical partial pressure of carbon dioxide in pulmonary artery blood: 46 mm Hg venous admixture -the partial pressure of oxygen in arterial blood of the systemic circulation is lower than the partial pressure of oxygen leaving the pulmonary capillaries -some deoxygenated venous blood from the bronchial circulation is mixed with oxygenated venous blood from the pulmonary circulation -diffusing capacity *the rate of gas diffusion in fluid depends on: -the solubility of the gas in the fluid -the surface area available for diffusion *carbon dioxide is about 20-fold more soluble in water than is oxygen -to achieve the same diffusion rates, larger partial pressure gradients of oxygen are needed than of carbon dioxide * diffusing capacities at rest -oxygen: about 20 ml/min/mm Hg -carbon dioxide: about 400 ml/min/mm Hg  * diffusing capacities during exercise -oxygen: maximum of about 65 ml/min/mm Hg -carbon dioxide: about 1250 ml/min/mm Hg -basis of increased diffusing capacity: *all pulmonary capillaries open *dilation of capillaries (increased surface area for diffusion) *better ventilation-perfusion ratio (below) gas exchange in systemic capillaries *interstitial fluid partial pressure of oxygen averages about 40 mm Hg *the partial pressure of oxygen in blood arriving at systemic capillaries averages about 95 mm Hg *if tissue oxygen consumption increases, a greater rate of blood flow can maintain the oxygen level *cells need a partial pressure of oxygen of about 1-3 mm Hg; probably average >20 mm Hg *the partial pressure of oxygen in blood leaving systemic capillaries averages about 40 mm Hg *tissue partial pressure of carbon dioxide is about 45 mm Hg *arterial blood arriving at systemic capillaries: PCO2 is about 40 mm Hg *venous blood leaving systemic capillaries: PCO2 is about 45 mm Hg