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AIRWAYS
- Conducting Zone → bringing air into and out of the lungs while warming, humidifying and filtering a. Includes nose, nasopharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles b. 23 divisions starting from the trachea, to L/R mainstem bronchi…etc c. Lined with cilia and mucus-secreting cells ( think of escalator ) d. Contain smooth muscle innervated by i. Sympathetic→ adrenergic neurons activate β 2 receptor causing bronchodialation (via epinephrine) ii. Parasympathetic→ cholinergic neurons activate muscarinic receptors causing bronchoconstriction e. As diameter affects resistance, particular innervation has predictable effects on resistance and airflow f. Pharmacological interventions include use of epi/albuterol/isoproterenol
- Respiratory Zone→ responsible for gas exchange a. Includes anything with alveoli associated with it i. Respiratory bronchioles – have smooth muscle and cilia but are still part of respiratory zone due to occasional alveoli buds ii. Alveolar Ducts – completely lined with alveoli, no cilia, little/no smooth muscle iii. Alveolar Sacs – terminal end of the ducts; also lined with alveoli b. Approx 300million alveoli (diameter of one is 200μm c. Type I and Type II pneumocytes; Type II responsible for secretion of surfactant. d. Contain phagocytes called alveolar macrophages keeping alveoli free of dust/debris (in absence of cilia) thereafter they migrate to upper airway to be expectorated/swallowed
PULMONARY BLOOD FLOW
- Lungs receive full output from the right heart a. Pulmonary arteries branch and travel with the bronchi toward respiratory zone i. Branch into arterioles to pulmonary capillaries around alveoli
- Gravitational effects do not allow even flow thru the lungs (increasing flow from apex to base) and changes depending on the position of the pt (standing, supine, etc.)
- Regulation of flow is accomplished via arteriolar resistance
- Bronchial (conducting airway) Circulation is a very small fraction and is supplied by a direct branch of the aorta
(VT) Tidal Volume normal inspiration/expiration; approx 500ml (IRV) Inspiratory Reserve Volume air inspired above tidal volume; approx 3000ml (IC) Inspiratory Capacity tidal volume plus inspiratory reserve volume (500+3000=3500ml) (ERV) Expiratory Reserve Volume air expired past tidal volume; approx 1200ml (RV) Residual Volume gas remaining after full forced expiration; approx 1200ml (FRC) Functional Residual Capacity expiratory reserve volume plus residual volume (1200+1200=2400) **essentially the volume remaining in the lung after expiration of tidal volume
(VC) Vital Capacity inspiratory capacity plus expiratory reserve volume (3500+1200=4700) (TLC) Total Lung Capacity vital capacity plus residual volume (4700+1200 ≈ 6L )
STRUCTURE OF THE RESPIRATORY SYSTEM
LUNG VOLUMES AND CAPACITY
RESPIRATORY PHYSIOLOGY
Since residual volume cannot be measured with a spirometer, FRC cannot be measured with this method either, thus the helium dilution method or body plethysmograph method must be used.
- Helium Method →fixed helium is given to breathe and full volume can be calculated based on concentration change C 1 · V 1 = C 2 · (V 1 + V 2 )
- Body Plethysmograph Method → uses Boyle’s Law (PV=constant) to define volume by placing the pt in a box. After breathing out a normal tidal volume, their mouth is closed and forced to inspire at which time lung volume increases and box volume decreases which increases box pressure. This pressure can be measured and used to calculate FRC.
DEAD SPACE is the space that does NOT participate in gas exchange; can be split into anatomical and physiological
- Anatomical Dead Space a. Is the volume of the conducting airways which is approx 150ml thus a 500ml tidal volume has a functional 350ml
- Physiologic Dead Space a. the total volume of the lungs that does not participate in gas exchange (ventilation/perfusion deficit) b. normally this is the same as anatomical however, this may include alveoli that are ventilated with air but may not participate in gas exchange as seen in some pathologic conditions c. size is estimated based on three assumptions i. all expired CO 2 comes from respiration/alveoli ii. essentially no CO 2 in inspired air iii. physiologic dead space neither exchanges nor contributes to expired CO 2 d. If physiologic dead space is zero, than PECO2 equals PACO2 and if physiologic dead space is NOT zero, PECO2 will be less than PACO2. This concept/ratio is what can be used to measure physiologic dead space
VENTILATION
1. Ventilation rates a. Amount of air moved thru the lungs per unit time – can be expressed as minute or alveolar ventilation where alveolar corrects for the dead space
- Alveolar Ventilation Rates a. Describes the relationship between alveolar ventilation and alveolar Pco 2
b. K is a constant (863mmHg) for conditions of BTPS (body temp, ambient press and gas saturated with water vapor) c. CRITICAL POINT→ if CO2 is constant then PACO2 is determined directly by alveolar ventilation ( A) i. If the CO 2 production was in fact constant, the relationship b/w A and PACO2 would be inverse or hyperbolic ii. Thus, if CO 2 production were to double, in order to maintain PACO2 , alveolar ventilation would also have to double.
VD = VT PACO2 - PECO
PACO
Minute Ventilation = VT breaths per minute Alveolar Ventilation = V’A = (VT-VD) breaths per minute
V’A = V’CO2 K
PACO2 - OR- PACO2^ =^ V’CO2^ ^ K
A
- Compliance of the Chest Wall a. Normally the intrapleural space is negative created by the force of recoil from the lung as well as the force of the chest wall to spring out b. This negative pressure prevents lung collapse i. A pneumothorax breaks this phenomenon; negative pressure is lost and the lung collapses on itself
- Pressure-Volume Curve now INCLUDING the Chest Wall a. The compliance (slope) for chest wall alone is very similar to the lung alone b. When compliance is measured together, it is much less (smaller/flatter slope) c. At FRC , the force of the lungs recoil and chest springing out are equal , hence airway pressure = ZERO d. Less than FRC , the lung recoil is less but chest spring out is greater, hence tendency toward Expanding e. More than FRC , lung recoil is more and chest spring out is less, hence tendency toward Collapse
- Changes in Lung Compliance a. Emphysema→ increased lung compliance i. Loss/decrease in elastic fibers associated with an increased compliance slope ii. This phenomenon results in loss of recoil force which affects the should-be equal pressure at FRC, now more volume is needed to expand the lungs more to increase recoil force to balance against chest springing force THUS: seeks a new higher FRC where opposing forces can be balanced b. Fibrosis→ decrease in lung compliance i. So called “restrictive disease”; stiffening of lung tissue associated with a decrease in slope ii. Results in an increase in recoil force where a lower volume of air is needed to create the force that will balance the chest springing force THUS: seeks a lower FRC where forces can be balanced
- Surface Tension of Alveoli a. Lined with a fluid whose intermolecular forces work to maintain the surface tension needed to prevent alveolar collapse b. Law of Laplace →
Note that radius and collapse pressure are inverse; as radius decreases, collapse pressure increases
- Surfactant a. Most important constituent is dialmitoyl phosphatidacholine (DPCC), s ecreted by Type-II alveolar cells b. Reduces surface tension based on amphipathic nature (opposite poles are hydrophobic and hydrophilic) c. It also increases lung compliance and in its absence, atelectasis will occur d. Neonatal Respiratory Distress Syndrome i. Lacking surfactant ii. Surfactant production begins in week 24 and is complete by week 35
AIRFLOW, PRESSURE AND RESISTANCE RELATIONSHIPS
- Flow → is analogous to blood flow where pressure difference is the driving force
P = 2T
R
P = Alveolar Collapse Pressure (dynes/cm^2 ) T = Surface Tension (dynes/cm) R = Radius of alveoli (cm)
Q= ΔP
R
Q = Airflow ΔP = Pressure gradient (b/w mouth and alveoli R = Airway resistance
- Resistance → determined by Poiseullie’s Law
a. note the 4th^ power relationship with radius and its dramatic impact on resistance b. The medium-sized bronchi are the site of greatest resistance _(think of resistance in parallel)_
- Changes in Airway Resistance a. ANS i. Sympathetic→ adrenergic neurons activate β 2 receptor causing bronchodialation (via epinephrine) ii. Parasympathetic→ cholinergic neurons activate muscarinic receptors causing bronchoconstriction b. Lung Volume i. Increasing lung volume exerts radial traction on the airway causing it to expand thus decreasing resistance
c. Viscosity of Inspired Air ( η )
i. Really only seen with deep sea diving where large depth increases viscosity and the use of helium to counteract this
BREATING CYCLE **note that transmural pressure is measured as alveolar minus intrapleural pressure, so positive is an expanding (outward) pressure and a negative pressure is collapsing (inward)
- Rest → the period between breathing cycles and diaphragm is at equilibrium position a. Alveolar pressure is equal to atmospheric pressure (aka – zero pressure) b. Intrapleural pressure is negative (-5cmH 2 O) c. Transmural Pressure is positive (+5cmH 2 O → [alveolar – intrapleural] = [ 0 – - 5 ] = +5 ) d. Also remember that the volume at this point is known as the FRC
- Inspiration a. Alveolar pressure falls below atmospheric (-1) and will drive air inside until pressure re-equalizes b. Intrapleural pressure becomes more negative (-8) due to an increase in lung recoil & neg. alveolar pressure c. The extent of intrapleural pressure changes is known as dynamic compliance
- Expiration a. Alveolar pressure become positive as the lung recoils (passive) b. At the end of expiration, all volumes and pressures return to resting values; ready to begin new cycle!
- Forced Expiration a. Airway, Alveolar and Intrapleural pressures are dramatically increased to +25, +35 and +20 respectively b. As long as the transmural pressure remains positive, a high intrapleural pressure will collapse the lungs c. COPD →slow breathing and pursed lips keeps airway pressure high to avoid collapse (by maintaining transmural pressure)
R= 8 ηl
πr
4
η = viscosity of inspired air l = length of the airway r = radius of the airway R = airway resistance
Overview of Gas Transport in the Lungs
- Gas Transport a. The slight discrepancy between alveolar gas concentrations and systemic arteries is due to the Physiologic Shunt which is the small fraction of pulmonary blood flow that bypasses the alveoli and there is not arterialized i. The shunt has TWO sources of “non-perfused” blood: 1. bronchial blood flow and a small portion of coronary venous flow draining directly into the left ventricle rather than going to the lungs to be oxygenated, thus non-perfused blood creates this minor discrepancy ii. The shunt is increased in several pathologic conditions (ventilation/perfusion deficit) in which case equilibration between capillary and alveoli is hindered increasing the A → a difference
- small shunt has a small A→a difference
- large shunt has a large A→a difference
- Diffusion/Perfusion Limited Gas Exchange a. Diffusion Limited →gas exchange is limited by the diffusion process i. Seen in CO, O 2 in strenuous exercise, emphysema and fibrosis ii. In such a situation, the partial pressure gradient is MAINTAINED throughout the capillary hence diffusion continues along the capillary, thus this process is limited by the inert speed of diffusion iii. CO 2 in particular is quickly protein-bound therefore not contributing to PaCO2 hence maintenance b. Perfusion Limited → gas exchange is limited by the passing blood or perfusion i. This is normally seen with N 2 O, CO 2 and O 2 with resting pt’s ii. Due to the fact that the partial pressure gradient quickly dissipates, the only way to get more gas into the blood is to supply more blood per unit time and allow “more saturation” to occur c. Oxygen Transport at High Altitudes i. at high altitudes, barometric pressure is reduced which reduces PAO2 from 100mmHg to 50mmHg ii. this reduction causes a decrease in the partial pressure gradient thus diffusion of O 2 across the capillary is reduced to a point where instead of need 1/4th^ second to transport it needs nearly the entire ¾ second as the capillary passes the alveoli iii. this phenomenon is dramatically exacerbated by fibrosis leaving PaO2 at levels as low as 30mmHg which seriously impairs O 2 delivery to the tissues
PVO2 – 40
PVCO2 – 46
PaO2 – 100
PaCO2 – 40
Dry Inspired Air
PO2 – 160
PCO2 – 40
Systemic Arterial Blood
Mixed Venous Blood
Humidified Tracheal Air
PO2 – 100
Alveolar Air PCO2 – 40
PAO2 – 100
PACO2 – 40
FORMS OF OXYGEN IN THE BLOOD
- Dissolved a. Accounts for 2% of the total O 2 in blood ( remember this is the only form that contributes to partial pressures) b. Using Henry’s Law and a solubility constant of 0.003mL O 2 /100mL blood and PaO2 of 100mmHg…
c. Clearly at the normal oxygen demand of 250mL/min this mechanism alone is grossly insufficient
- Bound to Hemoglobin a. Accounts for 98% of the total O 2 in the blood b. It is a globular protein with 4 subunits each of which carry a heme moiety either α or β c. Adult Hb (Hemoglobin A) is → α 2 β 2 where two subunits have α-chains and the other two have β-chains d. Oxygenated or deoxygenated Hb is called oxyhemoglobin and deoxyhemoglobin respectively e. The heme moieties on the subunits mush be in the ferrous state (Fe2+) in order to bind O 2 f. Several Variants of Hemoglobin Molecules i. Methemoglobin →when the heme moiety is in the ferric state (Fe3+) 1. in this state, heme CANNOT bind oxygen 2. congenital absence of methemeoglobin reductase→ needed for keeping the reduced state ii. Fetal Hemoglobin (HbF)
- beta chains replaced by gamma chains resulting in higher O 2 affinity
- replaced by HbA within the first year of life iii. Hemoglobin S (HbS)
1. causes sickle cell disease because the beta chains are abnormal ( denoted – α
A
S 2 )
- abnormal β-chain distorts the RBC shape in deoxy form resulting in occlusion/clotting and decreased O 2 affinity
O 2 BINDING CAPACITY AND CONTENT
1g of Hb can bind 1.34mL of O 2 and normal Hb concentration is 15g/100mL blood thus total O 2 binding capacity for blood is 20.1mL O 2 /100mL blood the actual content is calculated by adding the O 2 bound to Hb and the dissolved O 2
O 2 DELIVERY TO THE TISSUES
Determined by blood flow and O 2 content
OXYGEN TRANSPORT IN THE BLOOD
CX=PX Soulubility→ CO2= 100 . CO2= 0.3mL O 2 /100mL blood
HbO 2 = 20.1 98% = 19. then add the O 2 found in the other 2% (dissolved) 19.7 + 0.3 = 20.0mL O 2 /100mL blood
O 2 delivery = Cardiac Output O 2 content in the blood
PULMONARY BLOOD FLOW
- Pulmonary Blood Flow, Pressure and Resistance Relationships a. Lungs receive full cardiac output, less the coronary venous drainage to left ventricle from thesbian vein b. Pulmonary blood flow is directly proportionate to the pressure gradient between the left atrium and pulmonary vein and inversely proportionate to the resistance of the pulmonary vasculature
- Regulation of Pulmonary Blood Flow As in other places in the body, flow is regulated by controlling resistance of arterioles via smooth muscles In the pulmonary system, it is regulated by local vasoactive substances, especially O 2 a. Hypoxic Vasoconstriction i. PAO2 is the prominent regulatory factor; a DECREASE in PAO2 causes local vasoconstriction ii. This avoids a “wasting” of blood to an area where perfusion/ventilation is poor iii. The PAO2 directly affects vascular smooth muscle of the arterioles for a drop BELOW 70mmHg! iv. This phenomenon may be due to Ca-channels – OR– NOS and the cGMP production v. Global decreases in PAO2 can cause global vasoconstriction (high altitude) and in extreme cases, the increased resistance can cause RV-hypertrophy
- This global effect is seen in a fetus (this is normal and NOT pathologic) but disappears with the first breath of a PAO2 at 100mmHg b. Arachadonic Acid
- Distribution of Pulmonary Blood Flow **In an upright position, flow is greatest in the lower lung due to the forces of gravity (in supine = even distribution) a. ZONE 1→ PA>Pa>PV due to low hydrostatics (PaO2 is Highest at 130mmHg) i. Normally arterial pressure is just high enough to keep capillaries open but if alveolar pressure is increased or arterial pressure decreases enough, capillaries will collapse thus not contributing to gas exchange and contributing to the physiologic dead space b. ZONE 2→ Pa>PA>PV due to higher hydrostatics i. Compression of capillaries is not an issue in this zone and flow is driven by the difference between arteriolar and alveolar pressures (and not between arteriolar and venous press. as in the periphery) c. ZONE 3→Pa>PV>PA due to highest hydrostatics (PaO2 is Lowest at 89mmHg) i. Gravitational effect is greatest to where arterial and venous pressures are greater than alveolar ii. This pressure causes the flow to be driven by pressure difference b/w artery and vein iii. At this zone, the greatest number of capillaries are open and flow is at a maximum
VENTILATION/PERFUSION
RELATIONSHIPS
Q = ΔP
R
ARACHADONIC ACID
Leukotrienes
airway constrictor
Prostaglandins
potent vasoDialator
Thromboxane A 2
powerful vasoConstrictor
Lipoxygenase Cyclooxygenase
4. Shunts a. Physiologic Shunt are reroutes of the blood as seen in the following examples… i. 2% of Cardiac Output bypasses the alveoli to directly supply the bronchi ii. coronary venous blood drains into left ventricle and never reaches the lungs (seen earlier in notes) b. Pathologic Shunting can also occur i. Right-to-Left Shunt can occur with a deficit in the septum of the heart where up to 50% of the cardiac output never reaches the pulmonary artery and hypoxemia always occurs 1. Hi-flow O 2 treatment is NOT effective (but can be used as a diagnostic tool) 2. CO 2 levels increase very minimally due to high sensitivity that causes ↑resps causing a blow-off of the excess CO 2 ii. Left-to-Right Shunt are more common and DO NOT cause hypoxemia caused by patent ductus arteriosis or trauma 1. if blood is shunted from the left heart to the right heart, the PaO2 will be slightly higher in the lungs and the effective cardiac output will be higher in the right heart vs. the left 5. Ventilation/Perfusion Ratios a. Normal Value Ratio i. Defined by the ratio between alveolar ventilation to pulmonary blood flow ii. the normal value is 0.8 (average across the lung) meaning the alveolar ventilation is 80% of the pulmonary blood and partial pressures of gasses in the alveoli are normal iii. flow but as we know already, this varies across the lungs just as flow does iv. NOTE: regional variations in ventilation are not as great as flow variations therefore the ratio is highest at the top (apex = 3.0) and lowest at the bottom (base = 0.6) 6. Ventilation/Perfusion Defect/Mismatch a mismatch of ventilation and perfusion caused by ventilation of regions that are not perfused (dead space) or perfusion of a non-ventilated region (shunt) and any combination of the two a. Dead Space→ vent an area that has no perfusion; can be seen with pulmonary embolism (occludes flow) b. High Ratio→ vent an area that has minimal perfusion; results in regionally High PO2 and Low PCO c. Shunt (V’=0)→ perfuse a region that is not being ventilated; i. airway obstruction would cause such a situation ii. such a situation will have the same physiologic affect as a Right-to-Left cardiac shunt d. Low Ratio→ low ventilation relative to perfusion due to decreased ventilation
BRAIN STEM CONTROL OF BREATHING
**Controlled by the medulla and pons where the frequency of normal, involuntary breathing is regulated by three groups of neurons → medullay respiratory center, apneustic center and pneumotaxic center**
1. Medullary Respiratory Center (reticular formation) a. Composed of two groups (anatomically distinguishable) i. inspiratory center→ dorsal respiratory group; controls basic rhythm 1. peripheral chemoreceptor input from CN-IX and V and mechanoreceptor from CN-V 2. sends motor output to diaphragm via CN-V (phrenic nerve) ii. expiratory center→ ventral respiratory group
- as expiration is a predominantly passive process, in quiet breathing they are inactive though in exertion (exercise) they are very much active
- Apneustic Center (lower pons stimulates medulla) a. Apneusis is an abnormal breathing pattern w/ prolonged inspiratory gasps and brief expiratory movement b. Located in lower pons and stimulates the medulla
V’A
Q’
CONTROL OF BREATHING
RESPONSE TO EXERCISE
- Arterial PO2 and PCO a. As demand increases, ventilation increases to supply more O 2 but the partial pressures DO NOT CHANGE because the new addition of gasses are matched by the increased consumption b. It is possible that pH decreases due to lactic acid
- Venous PCO a. The venous PCO2 will surely increase due to increased skeletal muscle metabolism
- Muscle and Joint Receptors a. Activate early in exercise and activate inspiratory center to increase respiratory rate
- Cardiac Output a. Clearly increases with exercise and this is also reflected in pulmonary blood flow b. There is an associated ↓pulmonary vascular resistance and a more even distribution across the lungs
- O 2 -Hemoglobin Dissociation Curve a. Shift to the right (due to increase CO 2 , acidity and temperature) b. Results in decreased affinity of O 2 making delivery/unloading of O 2 easier
ADAPTION TO HIGH ALTITUDE ** Although barometric pressure and the partial pressure of oxygen will decrease, compensatory mechanisms will allow adaptation in order to maintain proper gas exchange**
- Hyperventilation a. If PO2 were to decrease enough (lower than 60mmHg) causing hypoxemia it would stimulate peripheral chemoreceptors that stimulate the medulla to ↑RR b. This results in “extra” CO 2 being expired results in respiratory alkalosis which will stimulate the central receptors to ↓RR i. They will initially offset each other but after several days hyperventilation will resume c. Respiratory alkalosis can be treated with carbonic anhydrase inhibitors (acetazolamide)
- Polycythemia a. Increased in RBC concentration that increases overall oxygen carrying capacity of the blood b. This is done by release of erythropoietin from the kidney in response to hypoxemia c. Note the increased viscosity can be disadvantageous
- 2,3-DPG a. increase the synthesis to help the unloading/delivery capacity for O 2 (shift to the right)
- Pulmonary Vasoconstriction a. Causes hypoxic vasoconstriction which increases pulmonary vascular resistance thus requiring the right heart to increase contractility in response to increased afterload (prolonged, this may cause hypertrophy)
- Acute Altitude Sickness a. sx/sx include→headache, fatigue, nausea, palpitations and insomnia b. these are attributable mainly to alkalosis and abate when the compensatory mechanisms are manifested
- HYPOXEMIA → a decrease in PaO2 and can be assessed by measuring the A – a difference a. Caused by high altitude, hypoventilation, diffusion defects, V’/Q/ defects and right to left shungs b. **refer to individual sections for details on how these can manifest as hypoxemia
- HYPOXIA → a decrease in oxygen delivery to the tissues a. Caused by decreased cardiac output, decreased PaO2 (hypoxemia) , anemia, CO-poisoning and Cyanide poisoning i. Cyanide can interfere with O 2 utilization in tissues
INTEGRATIVE FUNCTIONS
HYPOXEMIA AND HYPOXIA
