|
RT Corner.net |
 |
Page 1Introduction Lung respiratory and conducting zones
Alveoli have largest cross-sectional area Bronchioles have smooth muscle & cartilage 23 divisions of branches into ever smaller conduits. See Respiratory Function Mucous-secreting, ciliated cells line conducting zone airways. Large particles stop at nose, smaller ones caught in cilia, finest particles (like asbestos) make it into alveoli
Gas exchange can be divided into four functional components:
Respiratory quotient,
A = alveolar a = arterial blood v = venous blood
Non-Respiratory Functions of Respiratory System (upper airway includes nose, paranasal sinuses, naso- and oropharynx, larynx)
Respiratory Mechanics 300 million alveoli in lungs – 0.3 mm in diameter total surface area of lungs is about 75 m2 (size of tennis court) collateral ventilation – airflow between adjacent alveoli (via pores of Kohn) pleurisy – inflammation of pleural sac (painful “friction rub”) atmospheric pressure = 760 mmHg at sea level, decreases as altitude increases intra-alveolar pressure (intrapulmonary pressure) will equilibrate with atmospheric pressure intrapleural pressure (intrathoracic pressure) = 756 mmHg – vacuum; closed cavity **negative intra-alveolar, intrapleural pressures provide driving force for inhaling/exhaling transmural pressure – pressure across surface of lungs, = Palveolus - Ppleural space Also See Transairway/Transpulmonary/Transthoracic Pressures
Two Forces hold thoracic walls & lungs in close apposition (can’t expand thorax without expanding lungs)
intra-alveolar pressure = 760 mmHg, pushes out against intrapleural p. of 756 mmHg atmospheric pressure = 760 mmHg, pushes in against intrapleural p. Neither chest wall nor lungs are in their resting position (both are actively pushing against space) Pleural space has slightly negative pressure because chest is pulling out, lungs are pulling in, and there’s no extra fluid to fill expanded space Pneumothorax – air enters pleural cavity, pressure equalizes with atmospheric pressure, transmural pressure gradient is gone > lungs collapse, thoracic wall springs out
Before Inspiration– respiratory muscles are relaxed, no air is flowing, intra-alveolar p. = atm. p. Major inspiratory muscles (diaphragm, external intercostals) contract > thoracic cavity enlarges [Diaphragm is innervated by phrenic nerve; dome-shaped at rest, contracts & pulls down. Responsible for 75% of enlargement of thoracic cavity during inspiration. Contraction of external intercostals enlarges cavity in lateral and AP dimensions (elevate ribs when contracting)] As lungs expand, pressure decreases (to 759 mmHg) > air flows in (alveolar pressure is negative during inhalation, positive during exhalation) Intrapleural pressure drops to 754 mmHg (ensures that lungs will be fully expanded)
**Lung expansion is not caused by movement of air into lungs. With deeper contractions, contract diaphragm and external intercostals more forcefully & contract accessory inspiratory muscles (SCM, scalenes, alae nasi, small muscles of neck/head) to raise sternum & first 2 ribs At end of inspiration– inspiratory muscles relax, diaphragm is dome-shaped again, rib cage falls because of gravity once external intercostals relax, chest walls & stretched lungs recoil > volume decreases, pressure increases (to 761 mmHg) > air flows out During quiet breathing, expiration is passive (due to elastic recoil of lungs – no muscular/energy expenditure), whereas inspiration is always active. During heavy breathing – active expiration – contract abdominal muscles (increase intra-abdominal pressure > pushes diaphragm up > increases intrathoracic pressure), internal intercostal muscles (pull ribs downward, inward) > lungs are emptied more forcefully. During forceful expiration, intrapleural pressure exceeds atmospheric pressure, but lungs don’t collapse because intra-alveolar pressure increases, too (4 mmHg pressure gradient stays same)
Paralysis of intercostal muscles doesn’t affect breathing much, but paralysis of diaphragm = can’t breathe. Phrenic nerve is C3-C5, so patients with paralysis from neck down can still breathe. Air Flow Flow, V = ∆P/R ∆P = pressure gradient between atmosphere and alveoli R is primarily determined by radius Resistance of total airways circuit depends on #, length, cross-sectional area of conducting airways. Each terminal bronchiole has greater resistance to flow than trachea, but because of vast cross-sectional area, their overall contribution to total R is less than that of central airways (since bronchioles are arranged in parallel). In healthy patient, overall respiratory system has extremely low R Also See Compliance and Resistance Laminar vs. Turbulent Flow Flow can be laminar (low flow rate) or turbulent (fast flow rate) In small airways, flow is usually laminar For laminar flow, R = 8nl/nr4 (Poiseuille’s Law) η = viscosity, l = length Turbulent flow has different properties – driving pressure is proportional to square of flow (V2) Turbulence is most likely to occur with high velocity, large diameter. Volume of inflation of lung has important effect on airway resistance Pressure = (vol./compliance) + flow * resistance P = pressure required to breathe
Chronic Obstructive Pulmonary Disease (COPD) Narrowing of lumina of lower airways. When airway R increases, larger ∆P must be present to maintain same airflow. Expiration is more difficult than inspiration – “wheeze” as air is forced out through narrowed passages. In normal patients, smaller airways collapse – further outflow stops only if lung volume is very low (lungs can never be completely emptied) Chronic bronchitis – triggered by frequent exposure to cigarette smoke, pollution, other allergens. Airway lining thickens, mucous production increases, ciliary mucous elevator is immobilized by irritants. Increased mucous > bacterial infections Asthma – obstruction due to 1) thickening of walls b/c of inflammation, histamine-induced edema, 2) plugging of airways by very thick mucous, 3) airway hyperresponsiveness – trigger-induced spasms (allergens, irritants, infection). Most common chronic childhood disease. Emphysema – collapse of smaller airways, breakdown of alveolar walls (irreversible). Can happen because of 1) excessive release of trypsin from alveolar macrophages as defense against cigarette smoke irritants (lungs normally protected by α1-antitrypsin, but can be overwhelmed), 2) genetic inability to produce α1-antitrypsin (asthma and emphysema start in small airways – difficult to detect – ‘silent airways’)
(Need to overcome stiff/elastic recoil, frictional resistance, and inertiance)
Pulmonary elasticity
Also See Compliance Pulmonary elastic behavior depends on:
water molecules want to be close together – resist expansion of surface area (the greater the surface tension, the less compliant the lung). If alveoli were lined with water alone, surface tension would be so great, airways would collapse. pulmonary surfactant (lipid-protein mixture) lowers surface tension because water-surfactant attraction is not as strong as water-water > increases pulmonary compliance, reduces lung’s tendency to recoil. Produced by type II pneumocytes LaPlace’s Law à P = 2T/r P = inward-directed collapsing pressure, T = surface tension
Smaller airways are more likely to collapse than large ones because of greater surface tension (smaller r), but surfactant is more effective at lowering surface tension in smaller airways (less spread out). Surfactant stabilizes small alveoli. **Evidence of these two factors of lung elastic recoil is found in differing pressure-volume characteristics of saline-filled vs. air-filled lungs (saline-filled are easier to stretch than air-filled) You can have separate pressure-volume curves for chest wall, lungs – combine to get one for total respiratory system. Two structures are in series, interdependent – force required to inflate lung equals sum of pressure difference across lung and across chest wall. Interdependence of neighboring alveoli – surrounding alveoli resist collapse of another alveolus. Respiratory Distress Syndrome (RDS) – not enough type II cells to make surfactant
Work of Breathing Normally only required on inspiration Subdivided into compliance work (to expand lungs against lung/chest wall elastic forces); tissue resistance work (to overcome viscosity of lung/chest wall); airway resistance work Work = P * V
Measurements of Lung Volumes Also See: Pulmonary Function Tests 3-5% of total energy expended by body goes to breathing (heavy exercise – can increase 50-fold) in obstructive lung disease, up to 30% of body’s energy expenditure is for breathing – even at rest! Quiet breathing – 2,200 ml (expiration) – 2,700 ml (inspiration) tidal volume = 500 ml
Spirometry Spirometer – air-filled drum floating in water. Breathe into drum – records volume changes on spirogram. Most lung volume subdivisions can be measured directly from spirogram
Spirometry can measure TV, IRV, IC, ERV, VC (others measured indirectly, calculated) Forced vital capacity (FVC) maneuver – take in deepest breath possible, breathe out as much as possible. Data can be displayed as volume vs. time or as flow vs. volume if airways resistance is normal, FEV1 > 70% FVC Obstructive ventilatory defect – decreased air flow through tubes, normal tidal volume. Can be from 1) upper airways disease; 2) peripheral airways disease (from asthma, cystic fibrosis, chronic obstructive bronchitis, bronchiectasis); or 3) pulmonary parenchymal disease (emphysema). Restrictive ventilatory defect – normal flow, normal R, but small vital capacity, FVC, FEV1 are reduced (in ratio to each other). Can be chest wall, pleural, space-occupying intra-thoracic lesion, extra-thoracic conditions (obesity, pregnancy, ascites), or interstitial lung disease. Reduction in lung volumes below 80% of predicted values. Examples of lung volumes being smaller than predicted (restrictive defect):
Tests of gas exchange function of lungs Arterial blood gas determination (ABGs) – measurement of dissolved tensions of CO2 and O2 as well as pH of sample of arterial blood Pulse oximetry – photometric measurement of saturation of hemoglobin with O2. (non-invasive) DLCO – diffusing capacity of lung for carbon monoxide, usually done by ‘single breath’ method (DLCOsb). DLCO is affected by factors other than characteristics of gas exchange membrane; membrane thickness and increased surface area reduce DLCO.
Ventilation (V – ventilation, Q – perfusion) Volume of air breathed in and out in one minute Respiratory (minute) ventilation, V• = TV (ml/breath) * f, respiratory rate (breaths/min) At rest: 6,000 ml = 500 * 12 (6 L air breathed in and out per min.) With exercise, can increase 25-fold, to 150 L/min. TV is more important than respiratory rate when minute ventilation increases Dead space (VD) – volume of air-filled space incapable of gas exchange with blood =Anatomical dead space – 150ml. volume of conducting airways (350ml used for gas exchange) (equal to individual’s lean body weight in pounds) Alveolar ventilation, VA• = (TV – VD, dead space) * f, respiratory rate At rest: 4,200 ml = (500-150) * 12 Alveolar ventilation is about 5 L per minute = cardiac output (excellent transfer of gases) Normal respiratory rate is 12-15 breaths/minute
Each tidal breath does not completely fill/empty an alveolus – reservoir of gas ‘stored’ within alveoli that’s only gradually replenished. Volume = 3,000 ml – prevents fluctuation in alveolar gas tensions with each tidal breath. (alveolar ventilation is more important measurement than respiratory ventilation, since that’s where gas exchange is done) alveolar gas equation: PAO2 = FiO2 (PB – PH20) - (PACO2/R) solving for conditions at sea level & R = 0.8: PAO2 = 0.21(760-47) – (40/0.8) PAO2 = 100 obstructive lung disease – easy to fill lungs, hard to empty
restrictive lung disease – lungs are less compliant than normal
Increasing tidal volume is most efficient way to increase alveolar ventilation (increase respiratory rate and alveolar ventilation increases somewhat, but dead space is also increased) Not all alveoli are equally ventilated with air, perfused with blood = alveolar dead space (minimal in healthy patients, but can be lethal) ventilated, but don’t participate in gas transfer physiologic dead space – sum of anatomical & alveolar dead space
lower regions of lung are better ventilated than upper zones. Gravity is largely responsible. Pleural pressure is more negative at top of thoracic cavity – greater distending pressure for alveoli at top of lungs (top alveoli are larger in size). alveoli on bottom vs. top operate on different parts of a pressure-volume curve lower regions of lung are better perfused than upper zones. gravity is primary determinant. hydrostatic pressure gradient from top to bottom b/c lowest point in lung is 30 cm below highest point and pressure gradient of 30 cm water = 23 mmHg (15 mmHg above heart, 8 mmHg below heart)
Perfusion conditions in lung divided into three zones (a=pulm.art, A=intra-alveolar, v-pulm.vein) Zone 1: Pa < PA collapse of vessel before it crosses alveolus; no forward flow; doesn’t exist in normal lungs – might occur if person has hemorrhaged (BP, intravascular volume are low) Zone 2: Pa > PA > Pv flow driven by difference between arterial/alveolar pressure; primary area of distension, recruitment of vessels during exercise Zone 3: Pa > PA, Pv > PA continuous forward flow through distended vessels. Also See Pulmonary Blood Flow Matching of ventilation to perfusion there is not perfect matching of ventilation to perfusion in most alveoli. non-uniform distribution of both results in alveolar units with varying ratios of ventilation to perfusion (V/Q) alveoli at apex are overall poorly ventilated, perfused, but relatively better ventilated than perfused = high V/Q ratio if no perfusion but good ventilation, alveolar gas tensions will be same as in trachea (PAO2 = 150, PACO2 = 0). No effect on downstream gas tensions – part of dead space. But if there is some degree of perfusion PAO2 will be high, PACO2 will be low. alveoli at base are well ventilated, perfused, but better perfused than ventilated = low V/Q ratio if no ventilation, but some perfusion, alveolar gas tensions in unit will be same as those in mixed venous blood (no fresh air being added). PAO2 will be low, PACO2 will be high (blood exiting capillary will be low in O2, high in CO2) Units with low V/Q ratios have greater effect on overall gas exchange since they receive greater proportion of total pulmonary blood flow. A high V/Q unit can’t compensate for impact of low V/Q unit because it’s at flat part of S-shaped oxygen-hemoglobin dissociation curve – raises PO2, which results in more dissolved O2, but not much more HbO2 Any rise in PCO2 in arterial blood stimulates respiratory centers to increase alveolar ventilation > removal of CO2 through alveolar units with better V/Q ratios. Overventilation of these units can’t raise PaO2 since they are operating on flat upper portion of oxygen-Hb saturation curve Measurement of V/Q mismatch Also see: Pulmonary Shunt alveolar-arterial gradient – P(A-a)DO2 or A-a gradient – refers to pressure difference for O2 between alveolar conditions and arterial blood. Measurement of inefficiency of oxygen transfer.
Venous admixture – proportion of blood flowing through true right-to-left shunts or hypoventilated lungs (units with low V/Q ratios) – measure of wasted perfusion. Calculated from variation of shunt equation: Qva = CiO2 - CaO2 QT CiO2 - CvO2 Physiologic dead space – proportion of ventilation to both anatomic dead space and hypoperfused lung (high V/Q ratios) – measure of wasted ventilation. Calculated from equation: VD = PaCO2 - PECO2 VT PaCO2 Normal VD/VT ratio during resting breathing is 0.2 – 0.35 Gas Exchange CO2 and O2 are exchanged via simple diffusion – no active transporters – passively move down partial pressure gradients. When bulk movement of air ceases at terminal bronchioles, oxygen moves towards alveolus by diffusion, carbon dioxide diffuses away from alveolus. ideal gas law: PV=nRT n = # moles of gas, R = gas constant, T = absolute temperature Boyle’s Law: as volume of gas increases, pressure decreases Normal atmospheric air = 79% N2, 21% O2, a little CO2, pollutants, etc. Total atmospheric air pressure = 760 mmHg, of which 79% is from N2, 21% from O2, etc. Partial pressure of oxygen, PO2 is normally 160 mmHg (or torr) PN2 is normally 600 mmHg PCO2 is normally 0.03 mmHg Alveolar PO2 > pulmonary capillary PO2, so more oxygen goes into blood (diffuses until equal). Alveolar PO2 < atmospheric PO2 because 1) air is warmed to 37°C & saturated with water once it enters; water vapor adds 47 mmHg partial pressure, essentially ‘diluting’ partial pressure of other gases, 2) air inspired is mixed with lots of old, “dead” air (FRC). Only 1/7 of total alveolar air is replaced with each breath (<15% alveolar air is “fresh”). Average alveolar PO2 is 100 mmHg, remains nearly constant throughout cycle (as does blood PO2, as does oxygen in blood available to tissues) Average alveolar PCO2 is 40 mmHg, also fairly constant Average arterial PO2 is 100 mmHg, PCO2 is 40 mmHg Blood entering pulmonary capillaries is systemic venous blood (via pulmonary arteries), systemic venous blood PO2 = 40 mmHg, PCO2 = 46 mmHg O2 expelled from lungs = O2 extracted, used by tissues During exercise, venous blood PO2 can drop to 30 > increases ∆P at alveoli > more O2 diffuses from alveoli into blood.
Other factors influencing rate of gas transfer Partial pressure gradients are the main factor determining rate of gas transfer, but there are others. Surface area during exercise, pulmonary bp increases b/c of increased cardiac output > forces open many of previously closed pulmonary capillaries > increases surface area for gas exchange emphysema – SA reduced because many alveolar walls are lost – fewer, larger chambers (same when part of lung is collapsed or when part of lung is surgically removed) Wall thickness pulmonary edema – increased interstitial fluid between alveoli and pulmonary capillaries, caused by pulmonary inflammation or left-sided congestive heart failure pulmonary fibrosis – replacement of delicate lung tissue with thick fibrous tissue in response to certain irritants pneumonia – inflammatory fluid accumulation in/around alveoli. (viral/bacterial/aspirating food) increasing tidal volume increases surface area by stretching alveolar walls, and makes walls thinner. Clinical measurement of diffusion characteristics of alveolar-capillary membrane done by test called ‘diffusing capacity for carbon monoxide (DLCO).’ Alveolar-capillary membrane has vast surface area (70 m2) with very short distance (0.5 microns) for diffusion. Layers of separation between air and blood:
Diffusion coefficient Rate of gas transfer is proportional to diffusion coefficient, D (related to solubility & MW) D is proportional to (solubility)/(sq. root MW) D for CO2 is 20x D for O2 because CO2 is far more soluble in body. Faster diffusion rate is offset by CO2’s smaller ∆P (6 mmHg) than O2 (60 mmHg), so CO2 & O2 diffusion more or less equilibrates. In diseased lung, O2 transfer is more seriously impaired than CO2 transfer because of the difference in diffusion coefficient.
Pulmonary caps and systemic caps are only two places in circulation where gas exchange occurs. Arterial systemic capillary blood: PO2 = 100 mmHg, PCO2 = 40 mmHg Venous systemic capillary blood: PO2 = 40 mmHg, PCO2 = 46 mmHg (same as tissue conditions) The more actively the cell is metabolizing, the more cellular PCO2 rises, PO2 drops – more O2 diffuses from blood into cells, more CO2 diffuses from cells into blood. Net diffusion of oxygen is from alveoli into blood, then from blood into tissues (CO2 – opposite)
GAS TRANSPORT Oxygen is present in blood in two forms total O2 content in arterial blood is 20 ml O2/100 ml blood Physically dissolved in plasma – only 1.5%, because oxygen is not very soluble in body fluids 0.003 ml O2/100ml blood can be dissolved for each mmHg of pressure, so normal dissolved O2 content of blood is 0.3 ml O2/100 ml. Tissue O2 consumption is 250 ml/min at rest, so need extra way to transport O2. PO2 is related to oxygen dissolved, not oxygen bound to Hb Chemically bound to hemoglobin (Hb) – 98.5% 19.7 ml O2/100 ml blood Hb + à HbO2 (reversible) Reduced hemoglobin oxyhemoglobin Hb binds reversibly with 1.34 ml O2 per gram of Hb. Normal Hb content = 15 grams
PO2 determines Hb saturation Each Hb molecule has 4 Fe, is capable of binding to 4 O. “fully saturated” if 4 O are bound. PO2 of blood is most important factor determining %Hb saturation (related to [O2 dissolved]) Law of mass action if blood PO2 is increased (i.e., in pulmonary caps), reaction shifts to right, get more HbO2. if blood PO2 is decreased (i.e., in systemic caps), HbO2 dissociated, releases its oxygen. O2-Hb dissociation curve is S-shaped, not linear. at PO2 = 100 mmHg, Hb. is 97.5% saturated even at PO2 = 60 mmHg, Hb. is 90% saturated from 60-760 mmHg PO2, Hb. saturation only changes 10% - provides margin of safety in O2-carrying capacity of blood. Even if PO2 falls to 60 mmHg (high altitudes, stuck in a vault, pathological conditions), body can maintain high %Hb saturation. Mixed venous blood carries substantial amount of O2 – reserve which can be unloaded under extreme conditions (exercise). at PO2 = 40 mmHg, Hb. is 75% saturated (resting systemic capillaries, venous blood) Hb saturation decreases as cell metabolism increases from PO2 = 0-60 mmHg, a small drop leads to a steep drop in %Hb saturation. during strenuous exercise, up to 85% of Hb. gives up its oxygen pulse oximeter can non-invasively measure Hb saturation
utilization coefficient - % of Hb that gives up its oxygen as it passes through tissue capillaries. Normal value = 25%, can increase up to 85% during exercise.
Hemoglobin as a storage unit **Hb. acts as “storage depot” for oxygen – removing oxygen from solution as soon as it enters blood from alveoli. (when oxygen is bound to Hb., it doesn’t count towards PO2). Once Hb is saturated as much as it can be for that PO2, then O2 coming into blood increases PO2 until it equilibrates with alveoli. **Hb. also helps get oxygen into tissues PO2 of systemic blood (95 torr) is higher than tissue PO2 (40 torr), so O2 diffuses across. PO2 drops > Hb has to release oxygen > PO2 increases. Diffusion continues until Hb can’t unload more oxygen, PvO2 = 40 torr until it reaches pulmonary capillary beds. tissue PO2 is affected by rate of blood flow past tissues & rate of tissue metabolism. Hb plays role in total quantity of oxygen blood can pick up in lungs or drop off in tissues. If Hb levels are reduced by 50% (i.e., with anemia), O2-carrying capacity of blood drops by 50%.
Other factors affecting Hb-O2 affinity Oxyhemoglobin Dissociation Curve PO2 is most important factor affecting Hb-O2, but there are others… Increased PCO2 – shifts O2-Hb curve to right (less HbO2 at a given PO2) Decreased pH (increased acidity) – shifts O2-Hb curve to right CO2 and H2CO3
Bohr effect – CO2 & H+ can combine reversibly with Hb at site other than O2 binding site – reduces O2 affinity. Important in enhancing oxygenation of blood in lungs, releasing oxygen at tissues. Increased temperature – shifts O2-Hb curve to right (exercising muscles generate heat, demand more O2) **Above three factors are only in systemic capillaries. Hb has higher affinity for oxygen in pulmonary capillaries than in systemic capillaries. Inside RBCs, 2,3-bisphosphoglycerate (BPG) binds reversibly to Hb and reduces O2 affinity. 2,3-BPG is produced during RBC metabolism. Production gradually increases if Hb is chronically undersaturated (when HbO2 is low – high altitudes, anemia, some circulatory/respiratory diseases) Since 2,3-BPG is present throughout circulation, it not only increases HbO2’s ability to unload oxygen at the tissues, but it decreases its ability to load O2 from alveoli. (shifts curve to right)
Hb’s affinity for binding to CO is 240x that for oxygen. HbCO = carboxyhemoglobin Even small amounts of CO make cells O2-starved.
Carbon dioxide CO2 is transported in the blood in 3 ways total CO2 content in arterial blood is 59 ml O2/100 ml blood
taking place rapidly, in RBCs, with carbonic anhydrase catalyzing first reaction: CO2 + H20 à H2CO3 à H+ + HCO3- HCO3- is more soluble in blood than CO2. RBC has HCO3—Cl- carrier that passively facilitates diffusion of these ions (in opposite directions). Membrane is relatively impermeable to H+, so HCO3- diffuses alone. HCO3- diffuses out into plasma, Cl- diffuses into RBC = chloride shift Most H+ that’s left behind binds to Hb (reduced Hb has greater affinity for H+ than HbO2) – Hb helps keep acid-base balance between arterial & venous blood. Haldane effect – removing O2 from Hb increases its ability to pick up CO2, H+
CO2 dissociation curve – depicts relationship between PCO2 and total content of CO2 in blood. curve is much steeper than that for oxygen. 4% volume of CO2 is exchanged during normal transport of CO2 from tissues to lungs.
Respiratory exchange ratio (R) – ratio of CO2 output to O2 uptake. R = VCO2/ VO2 Under normal resting conditions, 4ml CO2: 5 ml O2 0.8 (80%) Page 2PULMONARY BLOOD FLOW Also See Pulmonary Blood Flow Physiologic anatomy of pulmonary circulation high flow (5L/min), low pressure (15 mmHg), low resistance (1-2 mmHg/L/min) circuit pulmonary artery extends only 5 cm above RV before dividing. Vessels are thin-walled, distensible – can accommodate most of stroke volume of RV. pulmonary capillaries form a dense network in alveolar walls – air spaces are nearly completely surrounded by flowing blood. (large surface area for gas exchange, short air-blood barrier) small pulmonary veins collect oxygenated blood from capillaries, run between lobules, form four large pulmonary veins
Pressures in pulmonary circulation pulmonary artery systolic pressure averages 25 mmHg, diastolic pressure averages 8 mmHg, mean pulmonary arterial pressure is 15 mmHg distribution of blood in lung is not complex – only need enough pressure to lift blood to top of lung work required of RV is much less than LV, RV is less muscular than LV pulmonary capillary pressure is estimated using flow-directed pulmonary artery (Swan-Ganz) catheter to measure back pressure from LA. Normal “pulmonary capillary wedge pressure” (PCWP) = 5 mmHg. [helps determine LA filling pressure (would be elevated with stenotic mitral valve, left-sided congestive heart failure)] pulmonary capillaries are surrounded by gas – subjected to pressure shifts occurring within alveolar spaces during ventilation. Swings in alveolar pressure may affect flow pressure in caps. if alveolar pressure is higher than pressure in capillary, it will collapse pressure difference between inside, outside of vessel = transmural pressure larger pulmonary arteries, veins (“extra-alveolar”) are subjected to much lower pressures than alveolar (smaller) vessels – pulled open as lung expands on inspiration
pulmonary vascular resistance (PVR) = input pressure – output pressure blood flow PVR is about one-tenth that of systemic circulation (1.7 mmHg/L/min). Resistance doesn’t need to be so high since there is no demand to regulate blood flow to various vascular beds/organs. Lungs have mechanisms to keep pressures low. With exercise, Q through lungs increases several fold, but pressure doesn’t rise because PVR decreases (via recruitment and distension of airways) as lung inflates, alveolar, extra-alveolar vessels are stretched.
Blood volume of lungs normal blood volume of lungs is 450 ml (70ml in capillaries) pulmonary vessels act as reservoir, accommodate up to twice as much blood volume. volume of blood in lungs varies with intrathoracic p. – high intrathoracic pressure expels blood from lungs; LV failure causes pooling of blood in lungs > rise in pulmonary p.
Factors affecting vascular resistance Passive changes in vascular resistance pulmonary arterial pressure (PAP) increase > PVR decreases LA pressure increases > PVR decreases blood volume increases > PVR decreases transpulmonary pressure increases > PVR increases Active changes in vascular resistance – vessels are reactive because of smooth muscle in walls Vasoconstriction: alveolar hypoxia – most potent stimulus causing vasoconstriction (adaptive mechanism to match best ventilation with best perfusion) PVR increases acidemia – PVR increases humoral substances – histamine, prostaglandin F2a Vasodilation: humoral substances – ACh, prostaglandin E1, nitric oxide, bradykinin **ANS stimulation has no effect on human PVR
Additional functions of pulmonary circulation blood volume storage – change from standing to lying posture filtration – stray blood clots metabolic – biologic activation (angiotensin I to II by ACE), inactivation (bradykinin, serotonin, PGE1, PGE2, PGF2α)
CONTROL OF RESPIRATION Also see Regulation of Ventilation “Pacemaker” activity for respiration is in respiratory control centers of brain. Neural control of respiration includes:
both voluntary (i.e., with speech) & involuntary (i.e., sneeze/cough) control. The medullary respiratory center is the primary respiratory control center; provides output to respiratory muscles. Two other centers, in pons, apneustic center, pneumotaxic center – influence output from primary center. Cell bodies for neuronal fibers of phrenic, intercostals nerves are in spinal cord. Impulses from medullary center terminate there à stimulate nerves for inspiratory muscles. When neurons are not firing, inspiratory muscles relax and expiration occurs.
Medullary respiratory center *Dorsal respiratory group (DRG) – nucleus tractus solitarius; mostly inspiratory neurons, terminate on motor neurons that supply inspiratory muscles (initial processing station for feedback from peripheral sensors) *Ventral respiratory group (VRG) – nucleus retroambiguus; both inspiratory & expiratory neurons – both remain inactive during quiet breathing. Called into play by DRG as ‘overdrive’ mechanism. Especially important in active expiration. Only during active expiration do impulses travel to expiratory muscles.
Generation of respiratory rhythm comes from rostral ventromedial medulla, near upper (head) end of VRG. Drives rate at which inspiratory neurons fire. Rhythm starts with latent period of several seconds, followed by APs, which crescendo over a few seconds – leading to ‘ramp’ pattern of inspiratory muscle activity.
Pontine centers exert ‘fine tuning’ influences on medullary center à ensure normal, smooth breathing, influence timing of switching between inspiration & expiration. Pneumotaxic center (upper pons) sends impulses to DRG to ‘turn off’ inspiratory neurons. Apneustic center (lower pons) prevents inspiratory neurons from being turned off. Of the two, the pneumotaxic center dominates. Without pneumotaxic ‘brakes,’ apneusis = prolonged inspiratory gasps with very brief interrupting expirations. (can occur with severe brain damage)
Cortex – involved in voluntary control of respiration Hypothalamus, limbic system – can alter pattern of breathing, i.e., affective states like fear, rage.
Respiratory effects of brainstem transections *rostral to pons (top) – little effect on spontaneous respiratory rhythm *mid-pontine– eliminates neurons associated with pontine respiratory group, removing tonic excitation, resulting in slowed frequency, increased tidal volume. Vagus is also transected here – input from lung stretch receptors is lost, resulting in apneusis *pontomedullary transection – irregular breathing pattern of gasping (loss of vagal afferents has no effect) *transection of spinal cord – eliminates all descending drive, results in apnea
Sensors Central chemoreceptors near ventral surface of medulla in vicinity of exit of 9th and 10th CNs distinct from respiratory center neurons bathed in brain ECF, respond to changes in [H+] (composition of ECF determined by CSF, local blood flow, and local metabolism) CSF contains less protein than blood = poorer buffering capacity. Change in PCO2 will change pH of CSF more than it changes pH of blood.
Peripheral chemoreceptors Carotid bodies (most important), aortic bodies Respond primarily to decreases in PO2 – less so to decreases in pH, increases in PACO2. When PaO2 falls below 100 torr, rapid response; below 60 torr – dramatic response Glomus cells in receptor release catecholamines that stimulate glossopharyngeal nerves
Pulmonary stretch receptors Airway smooth muscle Discharge in response to distension of the lung; activity sustained with lung inflation Impulse travels in vagus Hering-Breuer reflex – when VT > 1 L (during exercise, etc.), pulmonary stretch receptors in small muscle of airways are activated à APs travel through afferent nerve fibers to medullary center, inhibit inspiratory neurons. (negative feedback to keep lungs from being over-inflated)
Irritant receptors
“J” receptors
Other receptors
|
