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Objectives: Structure and non-respiratory functions of the lung

01. 02. 03. Describe the structure and general functions of the respiratory system Identify the mechanism by which particles are cleared from the airways. Describe the non-respiratory functions of the lung. Describe mechanisms for clearance of vasoactive substances from the blood during passage through the lung. Identify a substance that is almost completely cleared and one that is not cleared to any significant extent. Be able to estimate the alveolar oxygen partial , and PAO2, pressure, PO2, PIO2using the simplified form of the alveolar gas equation.

04.

Alveolar ventilation 05.

06. Define partial pressure and fractional concentration as they apply to gases in air, list normal values for each for O2, CO2, and N2. List the normal alveolar, arterial, and mixed venous blood gas values for PO2, SatO2, PCO2, HCO3, and pH. Draw a normal spirogram, labeling the four lung volumes and four capacities. List the volumes that comprise each of the four capacities. Identify which volume and capacities cannot be measured by spirometry. Define the mechanisms that determine the clinically important boundaries of lung volume (i.e., TLC, FRC, and RV). Contrast the causes and characteristics of restrictive and obstructive lung disease, including the abnormalities in lung volumes are associated with each. Define and contrast the following terms: anatomic dead space, physiologic dead space, wasted ventilation, and total ventilation per minute and alveolar minute ventilation. Calculate these volumes by using the proper formulas. Contrast the proportional relationship between alveolar ventilation and the arterial blood gases PCO2 and PO2. Define the following terms: hypoventilation, hyperventilation, hypercapnea, eupnea, hypopnea, and hyperpnea. Identify hypo and hyperventilation based on concentrations of PCO2

07.

08.

09.

10.

11.

12.

Mechanics of respiration
13. On one page, diagram the lung volume, tracheal pressure, alveolar pressure, and pleural pressure during a normal quiet breathing cycle. Identify on the figure the onset of inspiration, cessation of inspiration, and cessation of expiration. Relate the pleural and airway pressure values to the movement of air.

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14.

Identify the forces that generate the negative intra-pleural pressure, and predict the direction that the lung and chest wall will move if air is introduced into the pleural cavity (pneumothorax) when the lung is at functional residual volume. Discuss the effect of the elastic properties of the chest wall and the lung on functional residual capacity. Define compliance (lung and chest wall) and identify two common clinical conditions in which compliance is higher or lower than normal. Calculate compliance by using the formula. Draw a normal pulmonary pressure volume curve (starting from residual volume to total lung capacity and back to residual volume), labeling the inflation and deflation limbs. Explain the cause and significance of the hysteresis in the curves. Define surface tension as it applies to the lungs, including the effects of alveolar size and the role of surfactants. Define athelectasis and the role of surfactants in preventing it. Based on changes in FEV, FEV1, FVC, TLC, and flow volume curves, characterize the pathology as a restrictive and/or obstructive lung disease. Describe how FRC and residual volumes are altered in each case. Describe how airway resistance alters dynamic lung compliance. Describe the roles of airway diameter and turbulent flow on airway resistance. Define dynamic airway compression, and use this principle to explain the shift in the shape of flow volume curves that occur with COPD (chronic obstructive pulmonary disease).

15.

16.

17.

18.

19. 20. 21.

Diffusion of gases
22. 23. State the Ficks law for diffusion and determine the limitations of gas transfer Define oxygen diffusing capacity, and describe the use of carbon monoxide to determine oxygen diffusion capacity. Name the factors that affect diffusive transfer of gas.

24.

Pulmonary circulation
25. Contrast the systemic and pulmonary circulations with regards to pressures, resistance to blood flow, and response to hypoxia. Define zones I, II, and III in the lung, with respect to pulmonary vascular pressure and alveolar pressure. Explain how the alveolar pressure , the blood flow and the gravity interfere in the function of each zone. Describe the roles of distention and recruitment of pulmonary vessels in changing pulmonary blood flow and pulmonary vascular resistance. Identify the zones in which these two mechanisms apply. Describe the consequence of hypoxic pulmonary vasoconstriction on the distribution of pulmonary blood flow. Describe the effects of inspired nitric oxide on pulmonary vascular resistance and hypoxic vasoconstriction. Contrast the airway and vascular control mechanisms that help maintain a normal ventilation/perfusion ratio.

26.

27.

28.

29.

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30.

Explain the development of pulmonary edema by: a) increased hydrostatic pressure, b) increased permeability, c) impaired lymphatic outflow or increased central venous pressure, and d) hemodilution (e.g., with saline volume resuscitation).

Ventilation perfusion
31.
32. Name five causes of hypoxemia: hypoventilation, diffusion impairment, shunt, VA/Q mismatching, high altitude Identify hypoventilation based on concentrations of PCO2 and differentiate from other pathologies by using PCO2 and lung volumes Describe the consequences of diffusion impairment and the effect of an exercise test. Define right to left shunts and physiologic dead space (wasted ventilation). Describe the consequences of each for pulmonary gas exchange. Predict how abnormal ventilation/perfusion ratios will affect local alveolar oxygen and carbon dioxide pressures and exchange. Identify the average V/Q ratio in a normal lung. Explain how V/Q is affected by the vertical distribution of ventilation and perfusion in the lung. List the normal relative differences from the top to the base of the lung in alveolar and arterial PO2, PCO2, pH, and oxygen and CO2 exchange. Define two causes of abnormal V/Q distribution.

33. 34.

35.

36.
37.

38.

39.

Define the measurement of the alveolar to arterial PO2 difference, (A-a)DO2, the normal value for (A-a)DO2, and the significance of an elevated (A-a)DO2. Name three compensatory reflexes for V/Q inequality.

40.

Oxygen and carbon dioxide transport

41.
42. Define percent hemoglobin saturation, oxygen tension, oxygen content as they pertain to blood. Draw and label an oxyhemoglobin dissociation curve (hemoglobin oxygen equilibrium curve), showing the amount of dissolved oxygen and the relationships between oxygen partial pressure, hemoglobin saturation, and blood oxygen content. How does the shape of the oxyhemoglobin dissociation curve influence the uptake and delivery of oxygen? Define P50. and its relationship with the O2 Hb affinity Show how the oxyhemoglobin dissociation curve is affected by changes in blood temperature, pH, PCO2, and 2,3-DPG. Describe how anemia and carbon monoxide poisoning affect the shape of the oxyhemoglobin dissociation curve, PaO2, PCO2, and SaO2. List the forms in which carbon dioxide is carried in the blood. Identify the percentage of total CO2 transported as each form.
3

43.

44.

45.

46.

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47.

Describe the importance of the chloride shift in the transport of CO2 by the blood. Identify the enzyme that is essential to normal carbon dioxide transport by the blood and its location. Draw the carbon dioxide dissociation curves for oxy and deoxyhemoglobin. Define the interplay between CO2 and O2 binding on hemoglobin that causes the Haldane effect. Mention and explain causes of hypoxia: hypoxic hypoxia, anemic hypoxia, stagnat hypoxia, histotoxic hypoxia

48.

49.

Regulation of acid base equilibrium

49. Define respiratory acidosis and alkalosis and give clinical examples of each.

50.
51.

Describe the mechanism and function of respiratory acid base compensations.

Describe in quantitative terms the effect of ventilation on PCO2 according to the alveolar ventilation equation.

Control of respiration
52.
List the anatomical locations of chemoreceptors sensitive to changes in arterial PO2, PCO2, and pH that participate in the control of ventilation. Identify which chemoreceptor population is most important in sensing short-term (acute) and long-term (chronic) alterations in blood gases. Describe the respiratory drive in a COPD patient, and predict the change in respiratory drive when oxygen is given to a COPD patient. Describe the mechanisms for the shift in alveolar ventilation that occur immediately upon ascent to high altitude, after remaining at altitude for two weeks, and immediately upon return to sea level. Describe the physiological basis of shallow water blackout during a breath-hold dive. Describe the interaction of hypoxia and hypercapnia in the control of alveolar ventilation. Describe the significance of the feed forward control of ventilation (central command) during exercise, and the effects of exercise on arterial and mixed venous PCO2, PO2, and pH. Describe the effect of old age on lung volumes, lung and chest wall compliance, and blood gases.

53.

54.

55. 56. 57.

58.

Respiratory system under stress

59. 60. Describe the effect of exercise on respiratory system Describe the respiratory response to high altitude: acclimatization process

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I. Functions of Respiratory System A. The primary function of the lugs is to allow oxygen to move from the atmosphere into the blood and carbon dioxide to move out. Other functions of the lungs: 1. Synthesis of lipids, proteins and carbohydrates e.g. lipids pulmonary surfactant DPPC, proteins:collagen,elastine,enzymes,etc. 2. Defense mechanisms: Alveolar macrophages engulfs inhaled particles Alveolar macrophages secrete:enzymes, immune response components Surface enzymes:lisozymes found in leukocytes (bactericidal properties) ; Lymphocytes 3. Renoval of vasoactive substances by the endothelium of the vessels of Pulmonary circulation as: Prostaglandin E1,E2,F2:are completely removed in a single pass through the lungs: Norepinephrine: 30% in mixed blood is removed by lungs (epinephrine is unaffected) 4. Formation and release of chemical substances: Pulmonary surfactant Histamine,Prostaglandins, leukotrienes, Platelet activating factor, Serotonin,bradykinin, heparin, etc. 5. Coversion of hormones (Al All) 6. Endocrine function 7. Blood reservoir 8. Role in coagulation: produce heparin, tromboplastic substances, plasminogen activator. Over all function: destroy fibrin 9. Acid-base balance II. A. Structure of the Respiratory System The airways are divided in: 1. Conducting zone:trachea,bronchi and its subdivisions and bronchioles, (last structure is the terminal bronchiole) 2. Transition and Respiratory Zone: Begins with respiratory bronchiole (bronchiole with alveoli, alveolar ducts and alveoli)

B.

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CONDUCTING ZONE Z1 to z16 Anatomical dead space VD= 150 ml normally Supplied by the bronchial artery Cilia present Most airway resistance

RESPIRATORY ZONE Z 17-Z19 transitional zone Z 20-Z 23 respiratory zone Supplied by the pulmonary artery No cilia present Least airway resistance

Bronchi or central airways From Z1 to Z10 Contains cartilage Constrict or dilate independent Of lung volume

Bronchioles From Z11 to Z16 No cartilage Lung perenchyma dilates dependent of lung volume

B.

Symbols used in respiratory physiology table 19-2 Primary symbols C D F f P Q Q R S V V

Concentration or compliance Diffusion Fractional concentration of a gas Respiratory frequency Pressure or partial pressure Volume of blood Volume of blood per unit time (blood flow or perfusion) Gas exchange ratio or resistance Saturation Gas volume Volume of gas per unit time (gas flow or ventilation)

PHYSIOLOGY HANDOUT Secondary symbols A Alveolar a Arterial aw Airway B Barometric c Capillary DS Dead space E Expired I Inspired el Elastic L Lung p Physiologic pa Pulmonary artery pc Pulmonary capillary pc Pulmonary end capillary pl Pleural pv Pulmonary venous pw Pulmonary wedge s Shunt st Static t Time tm Transmural v Venous v Mixed venous Examples of combinations CL Lung compliance DLCO Lung diffusing capacity for carbon monoxide CvO2 Concentration of oxygen in mixed venous blood Barometric pressure PB Partial pressure of carbon dioxide PCO2 PA Alveolar pressure Partial pressure of oxygen PO2 Partial pressure of oxygen in arterial blood PaCO2 Partial pressure of carbon dioxide in alveoli PACO2 Partial pressure of oxygen in alveoli PAO2 Partial pressure of oxygen in inspired gas PIO2 Partial pressure of oxygen in mixed venous blood PvO2 PECO2 Partial pressure of carbon dioxide in expired gas Ppl Pleural pressure SaO2 Saturation of hemoglobin with oxygen in arterial blood Raw Airway resistance Fractional concentration of inspired oxygen FIO2 Volume of dead space air VDS VA / Q Alveolar ventilation - perfusion ratio Alveolar ventilation VA VE Expired minute ventilation Oxygen consumption per minute VO2 Note: A dot above a primary symbol denotes flow per unit time

RESPIRATORY

C.

Laws of gases 1. Boyles law At a constant temperature, the volume of a given quantity of any gas varies inversely as the pressure to which that gas is subjected. P1V1= P2V2 This is the basis for Plethysmography Pbox ix Vbox i=Pbox f x (Vbox i- V) Where: (Vbox i-V)= Vbox f
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2. CharlesLaw (Gay-Lussacs Law) Volume of a given mass of gas, at constant pressure, is directly proportional to the absolute temperature. 3. Daltons Law Total pressure exerted by a mixture of gases is equal to the sum of the separate or partial pressures that each gas would exert if it alone occupied the entire volume. PB=PN2 + PO2 + PH2O + PCO2 a. What is the PO2 in room air, at sea level: PO2=PB x FO2 Note:Atmospheric pressure (PH) at sea level=760 mmhg 02 concentration in normal room air=20.93% F02=fractional concentration of 02=.209

P02=760x.209 P02=158.8=160 mm hg b. What is the partial pressure of 02 when inspiring room air at sea level? Note:water vapor pressure must be subtracted from PB PI02=

c.

Calculation of PI02 at high altitude. Increased elevation does not affect 02 concentration but decreases atmospheric pressure. Subtract 120 mm Hg/mile of increased altitude. Example of P02 at one mile above sea level: PI02=[760- (120+47)]x .209=124.1 mm Hg

4. Henrys Law The total volume of that physically dissolved in a liquid depends on the partial pressure of the gas and in its solubility in the liquid. Volume of dissolved gas = Px Cs Volume of liquid Examples a. If the solubility coefficient of 02 is 0.003 ml and the partial pressure (Pa02) is 100 mmhg, how much 02 is physically dissolved? Dissolved 02=(0.003)(100)=0.3 ml dissolved b. if 100% 02 is breathed at a Pa02 of 650, how much of gas is physically dissolved? Dissolved 02=(0.003)(650)=1.95 ml dissolved where: P=partial pressure Cs=coefficient of solubility

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Ventilation is the process of moving air into and of the alveoli. Is usually defined too as the volume of fresh air entering the alveoli per minute, and is implicit that a similar volume of alveolar air is leaving the body per minute. I. Spirometry Device for measuring gas volume. Can meassure only the lugs volumes that the subject can exchange with it.

fig 3-4 A (Levitzky)

A. Spirometer types Volume-displacement spirometers Flow-sensing spirometers B. Lung Volumes and Capacites Tidal volume (VT): The volume of air inhaled or exhaled with each breath. In a 70 Kg adult is about 500 mI at rest Inspiratory reserve volume (IRV): Maximum volume of air that can be inhaled during a maximal forced inspiration starting at the end of a normal VT. About 3 L Expiratory reserve volume (ERV): Volume of air that can be expelled during a maximal forced expiration that starts at the end of a normal VT. About 1.2 L Residual volume (RV): Volume of air remaining in the lungs after a maximal expiration, about 1.2 L Total lung capacity (TLC): Volume of air in the lung after a maximal inspiratory effort. Is approximately of 6 L. TLC=VT+IRV+ERV+RV Vital capacity (VC): The maximum volume of air that can be expelled after a maximum Inspiration. VC= TLCRV Inspiratory capacity (IC): Maximum volume of air that can be inhaled to total lung capacity Over and above the tidal volume. IC=TV+IRV Functional residual capacity (FRC): Volume of air remaining in the lungs at the end of a normal tidal expiration. With respiratory muscles relaxed at this time, it represents the balance point between the inward elastic recoil of the lung and the outward elastic recoil of the chest wall. FRC=RV+ERV

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II. Pulmonary Lung disease Determination of lung volumes is helpful in the diagnosis and differentiation of pulmonary disease: Obstructive and restrictive. A. Restrictive Group of disorders that result in an increase in the connective tissue of the lung, increased elastic recoil and reduce compliance of the lung . e.g. Fibrosis, alveolar wall thickening. Decreased compliance, increasing difficulty to expand the lung. Increased elastic recoil. It is characterized by lower: FRC, TLC, VC, IVR, ERV, and even reduced RV B. Obstructive Resistance to airflow, airway may be obstructed (mocus) or destruction of connective and elastic tissue of the lung (emphysema): e.g. emphysema, chronic bronchitis, asthma Conditions that cause shortness of breath and obstruction of airflow Lung compliance is increased, elastic recoil is decreased. It is characterized by Increased: RV, FRC, TLC. Decreased: VC and ERV.

III. A.

Anatomical and Physiological dead space Anatomical dead space 1. An inspired breath entering the lungs is distributed, in part, to the alveoli where gas exchange occurs, but the rest of the breath remains in the conducting airways where there is no gas exchange. The conducting airways are referred as the anatomic dead space.

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Can be estimated by considering 1 mI of dead space per pound of body weight or more precisely by using the Fowlers method. 2. Fowlers method: Single breath of 100% 02 When the gas is exhaled through one-way valve, Nitrogen concentration at the mouth and the volume expired is monitored simultaneously. First part of the expired gas registers 0% nitrogen because is undiluted 100% 02 from the Anatomic dead space. Transition period is when the expired gas registers a slowly rising nitrogen concentration, this indicates that the gas is a mixture of dead space gas and alveolar gas. Final portion of expired gas comes solely from the the alveoli forming the alveolar plateau, where the nitrogen concentration is constant and less than 80% The volume of anatomical dead space is the volume expired between the beginning of the expiration and the midpoint of the transitional phase.

fig 2-6 (West)

B. Physiological dead space Is equal to the anatomical dead space plus the alveolar dead space Alveolar dead space is the volume of gas that enters unperfused alveoli per breath. 1. Calculated by using Bohr equation. C02 found in the mixed expired gas must come from alveoli that are both ventilated and perfused. Air coming from unperfused alveoli will not contribute to the C02 at the mixed expired air. VD = PaCO2 - PECO2 PaCO2

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IV. A.

Alveolar ventilation Minute volume volume of air entering and leaving through the nose or mouth per minute Alveolar ventilation volume of air entering and leaving per minute VT = VD+ VA VT=tidal volume VD=dead space volume VA=alveolar volume

Multiplying these volumes by number of breath/min (n):

Minute volume Alveolar ventilation

VE= VT x n VA= VA x n VA= VE VD dots over Vs indicate per minute

Dead space ventilation

VD= VD x n

B. Alveolar ventilation and Carbon Dioxide 1. 2. 3. The best way to evaluate edequate breathing in a patient is the partial pressure of Carbon dioxide. Normal PaC02= 40 mm Hg The concentration of C02 in the alveolar gas depends on the alveolar ventilation and on the rate of C02 production by the body. The volume of C02 expired per unit of time (VEC02) = VA x FAC02 PAC02 VC02 VA If PaC02 > 40 the patient is hypoventilating. If PaC02 < 40 the patient is hyperventilating.

In healthy person PAC02= Pa02

4.

Example: a. Calculate the normal minute ventilation Minute vantilation = VT x f VT= tidal volume 500 mI f =respiratory frequency (14-18 min) Minute ventilation = 500mI x 14/min =7000 mI/min = 7 L/min

Minute ventilation should be NO less 7.0 L/min b. Calculate the normal alveolar ventilation (VA) VA= (VT VD) n VT = 500mI VD = 150 mI n = 14-18 min =(500 mI 150 mI) 14/min = 350 x 14 = 4 900 mI/min = 4.9 l/min (normal is 4.9 to 5 L/min)

VA

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In normal individuals the Anatomical dead space is equeal to the Physiological dead space. The ratio of dead space to tidal volume (VD/VT) is approximately 0.2-0.35 VD VT C. = 150 500 = 1 3 = PaC02 = PAC02

PO2 and PCO2 during normal Ventilation

The below schema of the pulmonary and vascular arterial and venous system, shows the normal PO2 and PCO2 at different levels during normal ventilation.

D.

PO2 and PCO2 during hypoventilation.

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E. Example of patients : Determine if the patient is hyperventilating, hypoventilating or with normal alveolar ventilation Patient A: Dx: VT = 500 mI n = 15 PaC02 = 35

__________________________________ VT = 250 mI n = 30 PaC02 = 55

Patient B : Dx:

__________________________________ VT = 700 mI n = 20 PaC02 = 55

Patient C: Dx:

___________________________ , how is dead space? ____________

How is alveolar ventilation ? ___________________________________

Patient D:

VT = 450 mI

n = 12

PaC02 = 35

Dx: ___________________________ , how is the dead space? ___________

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I. A.

Respiratory Muscles Inspiratory muscles 1. Diaphragm Innervated by phrenic nerves At rest, the muscle descend 1-2 cm Deep inspiration, may descend 10 cm 2. External intercostals Lift ribs up and out (increase anteroposterior dimensions ) Innervated by intercostal nerves from T 1 to T 11 3. Accessory muscles Scalene, sternocleidomastoid Work at high levels of ventilation or with obstruction of the airway

B.

Expiratory muscles 1. Abdominal flat muscles Depress the lower ribs, pull down the anterior part of the lower chest, and compress the abdominal contents 2. Internal intercostal Depress the ribs and move them downward and inward Elastic properties of the lungs Like an elastic structure such as a balloon, an applied force is required for inflation, but the deflation to a low resting volume is a passive process and can ocour using energy stored by the elastic elements of the lung. 1. To produce the inflation

II. A.

Alveoli expand passively in response to an increase in distending pressure across the alveolar wall force per unit area (pressure) on the inside surface of the lungs must be greater than pressure on the outside surface of the lung 2. To produce the deflation Once the lungs are inflated, the pressure differences between the inside and outside of the lungs (often called elastic recoil pressure , abbr. Pel., or transpulmonary pressure) reflects the energy available to deflate the lungs.

B. Recoil tendencies
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The chest wall and lung have opposite recoil tendencies at rest. At the end of expiration the lung is tending to collapse and the chest wall is tending to spring out. This creates a negative intrapleural pressure (-5 cm water ) and holds the lung expanded

C. 1.

Volume- pressure relationships Transpulmonary pressure Absolute pressure difference between the inside and outside of the lung. Pel is always positive. Compliance a. Change in lung volume per change in transpulmonary pressure (Pel) b. Is the inverse of elastic recoil. Denotes the easy with which something can be stretched or distorted. Human lung compliance = 200mI/cm H2 0 Lung and chest wall compliance Useful data for clinical evaluations 1 --------------------------- = Total compliance 1 1 ----------------------------- + ---------------------Compliance of Complicance of the lung the chest wall

2.

3.

Specific compliance Compliance is volume dependent. It is greater at low lung volumes and lower at high lung volumes.

4.

Factors that affect lung compliance a. Reduced by: Fibrosis-proliferation of connective tissue. Pulmonary edema
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Musculoskeletal disorders Increased pulmonary venous pressure obesity. b. Increased by: Emphysema Age

5.

Measurement of the Pressure Volume curve

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6.

Problems a. Problem:Tidal volume =600 mI Intrapleural pressure before inspiration = 5 cm H2 0 Intrapleural pressure after inspiration = 8 cm H2 0 Calculate lung compliance

b. Problem: given that the compliance of an individuals lung 0.5 L/cm H20 and mean intrapleural pressure is 7 cm H2 0 , what is the volume of exhaled gas if intrapleural pressure rose to 5 cm H2 0?

c.

Problem: Given that the compliance of an individuals lung is 0.5 L/cm H2 0 and intrapleural pressure was- 10 cm H2 0. What is the new intrapleural pressure if this person exhaled 1.0 L?

III.

Surface tension Is produced by the cohesive forces between adjacent liquid molecules at the liquid-air interface. In an alveolus (or in bubble soap) the cohesive forces will produce a net force, which will tend to collapse the alveolus (or the buble). Within the bubble this force will be expressed as a pressure. Surface tension follows LaPlaces Law

A.

Laplaces law Give the relationship between the surface tension and the pressure inside the alveolus. P = 2T r P = Pressure T = Tension r = radius

What would happen if two alveoli of different size were connected to each other by common airway?. Assume that the surface tension of the two alveoli is equal. How will be the direction of the airflow ? Which alveolus has the largest pressure ?

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B. 1.

Role of surface tension and proper functioning of the lung Pressure within the airway during expiration is less than that which exists at the same lung volume during the process of inflation. Hysteresis is an elastic property of the lung. Is represented, in the pressure volume curve by the difference in volume during inflation and deflation at a given pressure.

2.

Lungs inflated with saline have a much larger compliance their air-filled lungs

Air filled: formation of an air-fluid interface Saline-filled no generation of interface

3.

Surface area vs. Surface tension

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When adding detergent, water or surfactant.

C.

Surfactant

Is a Dipalmitoilphosphatidyl choline (DPPC) produced by type II epithelial cells. The molecules of DPPC are hydrophilic at one end hydrophobic at the other. 1. Functions Decreases surface tension Stabilizes the alveolus Increases lung compliance Reduces the energy expenditure of breathing (from 2% with to 60% without surfactant) Helps to keep alveoli dry 2. Hyaline membrane disease (HMD) or Infant Respiratory Distress Syndrome (IRDS) Seen in premature infants due to lack of surfactant a. Predisposing factors: More common in males than in females More common in children of diabetic women (Insulin destroys enzymes that produce surfactant) Decreased thyroid function Decreased ACTH production Prematurity b. Prenatal diagnosis: Amniocentesis (lecithin /sphyngomielin ratio) Lecitin sphingomyelin ratio of 2.0 may indicate HMD c. Treatment Prenatal treatment underlying cause (in mother): Give cortisol to mother prior to birth to simulate type ll cells After baby is born: Positive end expiratory pressure ventilator (PEEP) lntroduce artificial surfactant NOTE: PEEP helps to keep alveolar pressure above atmospheric during expiration.

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3.

Adult respiratory distress Syndrome (ARDS) a. May be produced by: Hypoxia or hypoxemia (seen after trauma or surgery) Acidosis Abnormalities in pulmonary circulation Atelectasis Pulmonary edema Hyperoxia

D.

Interdependence: All alveoli are physically connected to surrounding alveoli. For one alveolus to collapse another alveolus must be stretched. The resistance to stretch will reduce the tendency of small alveoli to collapse.

IV.

Regional differences in ventilation Base of the lung is better ventilated Due to: Gravity effects Weight of the lung.

A.

1. At the end of normal expiration the mean value for intrapleural pressure is-5 cm H2 0 in the upright individual as we move towards the apex (against gravity) intrapleural pressure decreases (more negative) and as we go more toward the lung base pressure increases (more positive). 2. At the apex intrapleural pressure is- 2.5 cm H2 0, that represents a low pressure but a large force expanding the alveoli. Therefore, at the begining of inspiration alveoli at the apex are large and contain a large volume or air. 3. At the base intrapleural pressure is- 2.5 cm H2 0, that represents a higher pressure but a smaller force expanding the alveoli. Therefore, at the begining of inspiration alveoli at the base are small and contain a small volume or air.

Fig 7-8 & 7-9 (West)

V.

Airway resistance
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A. 1.

Resistance = P/Q Factors that determine airway resistance a. b c. d. r4, viscosity and density of the gas (increasing density and viscosity, increased resistance) Lung volume (Increased volume, decreased resistance ) State of contraction of airway smooth muscle. Sympathetic and parasympathetic, PACO2 and histamine Major site of airway resistance: medium size bronchi 80%

B.

Turbulent VS laminar flow Large airways Z1 Z 16 = turbulent flow Small airways Z 17 Z 23= laminar flow Dynamic compression of the airways

C.

A flow- volume curve can be recorded by making a subject inspire to total lung capacity and then exhale as hard as he can to residual volume;if this is performed repeatedly, with progressively more effort, airflow is increased at high lung volumes (effort dependent) but not at low lung volumes (effort independent ). At any given lung volume a certain flow rate can not be exceeded

1. A rise in intrapleural pressure at a given lung volume causes a rise in alveolar pressure, and a rise in alveolar pressure will cause an increase in airflow, if airway resistance is constant (V = P) During forced expiration; intrapleural pressure can rise above atmospheric pressure. When airway resistance dissipates pressure in the airways as gas flows toward the mouth, pressure on the outside of the airways can become greater than pressure on the inside of the airways. This transmural pressure difference, in turn, can compress the airway and increase airway resistance. Increases in Pel (e.g.with increase in lung volume) reduce the tendency for airway compression, for example,schema C in the lower figure.

Forced vital capacity (West pag. 153)

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Increases in the airway resistance will increase the tendency for airway compression. 2. Increasing the stiffness of the airways will reduce the tendency for airway compression. Completely rigid tubes would not be susceptible to airway compression. In contrast airways with weak walls will easily collapse when pressure outside is increased above pressure inside: 3. At high lung volumes airway compression does not normally occur: Pel is very high, and airway resistance is minimal.

D.

Forced Expiratory Volume -1/ Forced Vital Capacity

1. A forced vital capacity determination is accomplished under maximum patient muscle effort to insure maximum flow rates at all lung volume 2. FEV1 is the forced expiratory volume at one second. It is normally about 80 % of the FVC

3. FEV1 is a funtion of: lung size, elastic ability to expand the lungs, and conducting airway diameter (airway resistance). 4. The FVE 1/FVC ratio is good index of expiratory airway resistance Normal subject FVE 1/FVC is greater than 0.80 (at least 80% of FVC is expired in the first second. a. Obstructive disease FVE 1/FVC is below 0.80 b. Restrictive disease (such as fibrosis) both FEV and FVE1 are reduced but FEV 1/ FVC is normal or increased. 5. Maximum mid-expiratory flow rate (MMER25-75%) is the average rate of air flow measured between 25 and 75% of the total FVC. This measurement is often more sensitive than FVE 1 in detecting chronic diffuse obstrution.

E. 1.

How to determine if a problem is Restrictive or Obstrutive Restrictive disease: a. To determine a Restrictive problem, the FVC is obtained from the machine at ambient temperature (ATPS,AT=ambient temperature, PS=pressure standard) and has to be converted into BTPS (body temperature pressure standard) by multiplying by a conversion factor Vbtps= 1.073. Vatps
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Then divide the measured BTPS by the predicted volume (can be obtained from heigt/weigh charts) and multiply by 100 to get a percent.

Example: if the predicted volume is 5 liter and the one measured in the patient in BTPS is 4 liters then:

Measured FVC in BTPS Predicted VC

x 100

4 liters x 100 = 80 % VC 5 liters

If the % vital capacity < 80 = restrictive problem, restriction of expansion of chest. Is characterized by increased respiratory frequency decreased, tidal volume, FRC, TLC. There is difficulty in breathing in all the air. b. Examples of restrictive diseases diffuse interstitial pulmonary fibrosis atelectasis obesity broken ribs diseases of the pleura diseases of the chest wall neuromuscular disorders

2.

Obstructive: a. Obtaining the FEV1 by spirometry and dividing by VC and multiplying by 100 Example: FVE1 x 100 VC 65 x 100 = 76% 85

If the FEV1/VC % calculated is < 80% the problem is obstructive. Is characterized by decreased respiratory frequency, increased tidal volume, RV, FRC, TLC. b. Examples of obstructive diseases: COPD (emphysema, chronic bronchitis) Asthma Localized airway obstruction Tracheal obstruction Bronchial obstruction

F.

Flow-volume curves

(West pag. 110-113 and 153-154)

1. At high lung volumes the airflow rate is effort-dependent. At low lung volumes the expiratory flow is effortindependet. This is because resistance increases with increasing expiratory effort due to greater dynamic compression of the airways with more positive intrapleural pressure 2. Restrictive disease: both maximum flow rate and total volume exhaled are reduced. Flow rate is often abnormally hign during the latter part of expiration because of the increased lung recoil

3. Obstructive disease: are associated with high lung volume, and high residual volume because the airway closure occurs at high lung volumes. Flow rate is very low in relation to lung volume. During the effort
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independent part the curve is depressed inward (flow rates are low for any relative volume). asthma, bronchitis, emphysema.

Examples:

G.

Normal flow curves under different physiological conditions

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H.

Flow-volume loops help to distinguish between fixed and variable obstructions:

1. Fixed (intra or extrathoracic) obstruction: both the inspiratory and expiratory flow volume curves are truncated, indicating a decreased peak during expiratory and inspiratory flows.

2. Variable obstruction: when the changes in the transmural pressure gradient caused by the inspiratory or expiratory effort result in changes in the diameter of the obstruction. The loop can demonstrate when the obstruction is intra or extrathoracic. a. Variable extrathoracic obstruction: during forced expiration the cross-sectional area increases as the pressure inside the airway increases. Then the expiratory curve is not affected. During forced inspiration the pressure inside the upper airway decreases and the cross-sectional area will decrease, and the flow volume curve is truncated.

b. Variable intrathoracic obstruction: during forced expiration positive intrapleural pressure is produced and the cross-sectional area decreases reducing then the forced expiratory flow, during forced inspiration, the intrapleural pressure becomes more negative and the cross- sectional area increases, then flow-volume curves are not affected.

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The pulmonary circulation is characterized as a low pressure, low resistance and high compliance system. Comparison of the systemic and pulmonary circulations: Characteristics 1. Output 2. Blood volume 3. Pressure 4. Resistance 5. Place of resistance 6. Normal state 7. Gravity 8. State of vessels 9. Wall of the pump 10.Effect of hypoxia 11.Autonomic control 12.A-V anastomosis Systemic circulation 5-6 L/min 4.5 L high high arterioles constricted little effect maintains tone thick (LV) dilates capillaries marked (PS dilates, S constricts) none Pulmonary circulation 5-6 L/min 0.5 L low low evenly divided cap=vein=artery dilated marked effect constrict capillaries thin (RV) constrict capillaries minimal present (abundant at capillary level)

A.

Pulmonary vascular resistance

PVR = MPAP MLAP PBF

PVR = pulmonary vascular resistance MPAP = mean pulmonary arterial pressure MLAP = mean letf atrial pressure

PVR = 15-5 mm Hg / 6 L min = 1.6 SVR = 100 2 mm Hg / 6 L min = 16.3

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The low pulmonary vascular resistance is due to the fact that the pulmonary arterioles have relatively low smooth muscle arterial contractile tone and the pulmonary capillaries have a relatively large cross sectional area. 1. Lung volume and PVR:

Vessels are divided in alveolar and extraalveolar. At high lung volumes the resistance of the alveolar vessels increases. At low lung volumes the resistance of alveolar vessels decreases. At high lung volume the extraalveolar vesssels (larger arteries and veins) decrease the resistance, this is due to: a. The increase in the negativity of the intrapleural pressure that increases the transmural pressure distending the vessel. b. Radial traction. During forced expiration, at RV, intrapleural pressure becomes very positive and the resistance of extraalveolar vessels increases. When the resistances of the alveolar and extraalveolar vessels is added, resistance is lowest at functional residual capacity and increases at both high and low lung volumes.

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2. Recruitment and distensibility As the cardiac output increases, the pulmonary vascular resistance decreases. The mechanisms that explain this are: a. Recruitment: opening of unperfused vessels, it is the main mechanism to decrease the PVR when the artery pressure is raised from low levels b. Distention: increase in the radio of the vessels. It is the mechanism to decrease the PVR at relatively high vascular pressures.

B. Regional distribution of blood flow Determined by gravity effects and extravascular pressures. In the upright individual, blood flow decreases from the bottom to the top of the lung. 1. Zones of the lung.
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Zone 1 PA > Pa > Pv Pulmonary arterial pressure falls below alveolar pressure, Capillaries would be completely collapsed Theoretically this zone is ventilated but not perfused (alveolar dead space) This zone does not exists under normal conditions. Zone 2 Pa > PA > Pv Pulmonary arterial pressure increases becauses the hydrostatic effect and is greater than the PA Zone 3 Pa > Pv > PA Venous pressure exceeds alveolar pressure, the flow is determined by the arterial-venous pressure difference

C.

Hypoxic vasoconstriction Probable mechanism:direct action of hypoxia on vascular smooth muscle, or release of vassoactive subtances as histamine, angiotensisn, catecholamines, and protaglandins, inhibitors of NO. The effect of hypoxic vasoconstriction is to move the blood flow away from hypoxic zones of the lung. At high altitude, generalized vasoconstriction may occur.

D.

Pulmonary hypertension May be due to:

1. 2. 3.

Increase in left atrial pressure, e.g. mitral stenosis and left ventricular failure. Increase pulmonary blood flow,e,g.congenital left to right shunt, atrial septal defect, patent ductus arteriosus. Increase pulmonary vascular resistance (most common cause) a. Vasoconstrictive,e.g.decreased PA02 (high altitude) b. Obstructive,e.g.embolus c. Obliterative,e.g.emphysema

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E.

Pulmonary edema 1. Starling equation Qf = Kf {(Pc Pis ) o (pl is)} Types of pulmonary edema a. Interstitial: fluid in the interstitial space b. Alveolar: fluid comes into the alveoli

2.

3.

Mechanisms of pulmonary edema a. Increase in pulmonary capillary hydrostatic pressure (most common cause),e.g myocardial infarction,mitral stenosis,left ventricular failure, veno-occlusive disease, and fluid overload. b. Increased capillary permeability,e.g.sepsis,02 toxicity,ARDS (adult respiratory distress syndrome), endotoxins,inhaled toxins (S02,N02,Chloride). c. Lymph obstruction,e.g. silicosis,lymphatic CA, filariasis (parasite infection) d. Decreased interstitial pressure,e.g. rapid removal of pleural effusion of pneumothorax or hemothorax. e. Decreased colloid osmotic pressure e.g. overdilution by intravenous solutions, hypoproteinemia by renal failure. f. Idiopathic, e.g. HAPE (high altitude pulmonary edema), heroin addicts, pulmonary edema efter head injuries.

1. Ficks law for diffusion The Ficks law describes the factors that describe diffusion through the alveolar capillary membrane: A = area D = diffusion constant T = thickness of the membrane P1-P2= partial pressure difference

Vgas A D(P1-P2 ) T

Then the rate of diffusion is directly proportional to the area of the barrier, the diffusivity, and to the difference in concentration between the two sides. It is inversely proportional to the thickness of the membrane. The diffusion constant is directly proportional to the solubility of the gas and inversely proportional to the square root of the molecular weight of the gas. Oxygen is less dense than carbon dioxide but the solubility of CO2 in the liquid phase is about 24 times that of oxygen, for that reason CO2 diffuses about 20 times more rapidly than does O2 2. Diffusion and Perfusion limitation A. At resting conditions, red blood cells spend about 0.75 sec inside the pulmonary capillary. B. What happened when foreign gases such CO and N2 O are added to the alveolar gas ? a. CO moves very rapidly thought the alveolar-capillary membrane and combines chemically with hemoglobin (its affinity is 210 times that of O2 for hemoglobin), and because CO is not chemically dissolved in plasma its partial pressure doest not rise maintainig the partial pressure gradient through the alveolar capillary membrane. Because CO diffusion is limited only by its diffusivity and by the surface area and thickness of the barrier it is considered diffusion limited. b. N20 does not combine chemically with the Hb, then its partial pressure in the alveolar
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gas and in the blood equilibrates very rapidly (in about 0.1 sec)and no more N2O transfer occurs until new blood enters the pulmonary capillaries whith no N20. For that reason it is considered perfusion limited.

3.

Diffusion of oxygen

A. Blood enters the pulmonary capillaries with a PO2 of 40 mm Hg and in about 0.25 sec, PO2 has risen to a value equal to that in the alveolar gas.O2 moves easily through the alveolar capillary membrane and combines chemically whith Hb until saturates and then the PaO2 increases until equilibrate with the alveolar pressure. Under this normal condition, oxygen transfer is perfusion limited. B. During exercise the red blood cell spends much less time in the capillary, but the equilibrium of PO2 between gas and blood occurs (perfusion limited). C. When alveolar-capillary membrane is thicker (due to fibrosis or edema) O2 transport may be diffusion limited. D. During hypoxic hypoxia (arterial PO2 is depressed) the alveolar-capillary partial pressure gradient is decreased and PO2 takes longer to equilibrate. Then O2 becomes diffusion limited.

4.

Measurement of Diffusing Capacity Diffusing capacity is the rate at which oxygen or carbon monoxide is absorbed from the alveolar gas into the pulmonary capillaries (ml/min/mm Hg). Diffusion capacity of the lung DI = Vco P1-P2 The best form to measure diffusion capacity of the lung is to measure Carbon monoxide after administration by the following formula: Dlco2 = Vco Paco This is because the PCO in pulmonary capillaries is neglected

Dl02 = 1.23 DICO

This is useful to calculate the diffusion of the 02.

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The diffusion capacity of the lung CL for 02 or CO occurs in two stages: 1. 2. Diffusion through the blood gas barrier (including plasma and red cell interior) Reaction with hemoglobin

The summation of the two resistances produces a diffusion resistance

VENTILATION PERFUSION RELATIONSHIPS The amount of gas exchange in the lungs depends on: 1. The amount of ventilation reaching the alveoli per unit time (VA) 2. The amount of blood circulating through the lung capillaries per unit time (Q) B. Oxygen transport from air to tissues

Pl02 = 150 PA02 = 100-105 Pa02 = 90-95

Pcell 02 = 20-60

Pmitoch. 02 = 5-10

If a lab report gives the following values: Pa02 = PA02 = 92 80

What is your dx ? ______________________________________________________________

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Hypoxemia Decreased Pa02 (<90) Pa02 decreases with age, at 60 years is about 85 mm Hg. In a young adult 95 mmHg.

When Pa02 + PaC02= 130+ 2 it is considered to be hypoxemia whithout lung disease. This Only applies when breathing room air.

Mechanism that causes hypoxemia 1. hypoventilation 2. Impaired diffusion 3. Increased venous admixture or shunt 4. Uneven V/Q

1.

Hypoventilation Reduced fresh air going to the alveoli per unit time. Decreased P02 and Increased PaC02 (>40)

PC02 =

VC02 VA

Increasing the P02 of the inspired gas can easily abolish the hypoxemia. Causes: Depresion of respiratory center by drugs (barbiturates and morphine derivatives) or anesthesia. Diseases of the medulla or the spinal condusting pathways (poliomyelitis ) Diseases of the nerves as Guillain Barre syndrome, or of the neuromuscular junction As Myasthenia gravis. Disease of the respiratory muscles, thoracic cage or obstruction of the upper Aiways. Extreme obesity (pickwickian syndrome). 2. Diffusion Impairment Equilibration does not occur between the P02 in the pulmonary capillary blood and alveolar gas. Normal or low Pa02 at rest, but Pa02 descreaseswith exercise. Can be corrected by administering 100% 02. least common cause of hypoxemia

Causes: Fibrosis Interstitial pneumonia Connective tissue diseases as scleroderma, lupus erythematosus. 3. Increased venous admixture or Shunt Blood that enters the arterial system without receiving oxygen when passing through Ventilated areas of the lung. Pa02 is < 600 after 100% 02 a. Anatomical or true shunt b. Shunt-like effect
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Causes: Congenital heart disease (atrial or ventricular septal defects,patent ductus arteriosus) Intrapulmonary shunts (arterial-venous fistulas).

4.

Uneven V/Q Commonest cause difference Increased A a D02 (diffusion 02) a. Uneven V b. Uneven Q (increases VD alveolar ) In order to evaluate the ventilation/ perfusion inequality you simply look at the partial Pressure of 02 difference of alveolar and arterial pressure: PA02 _ pa02

Pa02 is obtainned from the arterial blood gas laboratory exam, but to know PA02 calculate Ot by using the following equaton (review): PA02 = PI02 PAC02 + F R PA02 = PI02 1.2 paC02 + F R = VC02 = 200 = 0.8 V02 250 1 = 1.2 0.8

PA02 = PI02 1.2 PaC02 + F

where F = PaC02 (1-R)FI02 = 2 to 5 mm Hg breathing room air

A. Consequences of high and VA/Q In order to understand the effect of V/Q inequality on blood gases, consider the following hypothetical alveolar- capillary units:

V/Q # 1. # 2. # 3. 1 zero infinity

P02 100 40 149

PC02 40 46 zero

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Unit with V/Q = 0 the alveolus has blood flow but no ventilation, the P02 and PC02 will equilibrate with systemic venous (pulmonary arterial) blood. Unit with V/Q = the alveolus has ventilation but no blood flow, does not exchange 02 or C02 and the final PA02 will be the same as dead space air, that is 150 mm Hg and C02 of zero. Most alveoli have VA/Q values whose composition is between VA/Q = and VA/Q = 0 The VA/Q ratio is a measure of mismatched ventilation and perfusion. An increase in ventilation (V) or a decrease in perfusion (Q), in any portion of the lung will result in an elevated V/Q ratio for that portion. The result will be an elevated alveolar P02 and a decreaseed PC02. The opposite will occur with a low V/Q ratio.

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PA02 = PAC02 = PAN2 = ___________ 713

V/Q = 1

PA02 = PAC02 = PAN2 = Note: there is hing N2 when V/Q is

_________
713

V/Q = 0 = 0

PA02 = PAC02 = PAN2 = ____________ 713

V/Q = 1 =

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B.

02-C02 diagram All possible P02 and PC02 values resulting from differences in VA/Q are characterized using VA/Q line. To construct this curve, a specific inspired and venous 02 and C02 composition is needed

C.

Regional distribution of gas and blood flow along the lung: In normal lungs, gas and blood are not distributed uniformly throughout the lung and this leads to differing ventilation perfusion ration (VA/Q) in diferrent regions of the lung. Both V and Q exhibit an increase from the apex of the lung to the base. However, the Gradient for perfusion is much greater. This means that VA/Q must increase from the base to the apex VA/Q at the apex = 3.3 VA/Q at the base = 0.63 As consequence of this low VA/Q at the base, the PA02 is lowest at the base.

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D.

Effects of Q on V02; effects of VA on VC02 a. For a given composition of blood entering the alveolus: uptake of 02 (V02) in any portion of the lungs will tend to increase as Q increases,but will be little influenced by VA. VC02 will tend to increase as VA increases but will be little influenced by Q b. Because V02 depends largely of Q, and VC02 depends largely on VA, it can be inferred that where ventilation is high and blood flow is low (high VA/Q),the elimination of C02 will be favored over the uptake of 02 (R is high). Conversely, when blood flow is high relative to ventilation (low VA/Q), the uptake of 02 will be greater than the elimination of C02(R is low).

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E.

Distribution of ventilation perfusion ratios

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Clinical examples

Patient A: Comes to ER with a PA02 = 70, PaC02 = 58 Patient has____________________________due to ________________________

Patient B: Pa02 = 70, PaC02 = 39 70< 90 = _____________________________ 70 + 39 = _________________ then it is consider a ____________________________ How is the paC02___________________, then is not a __________________________ You suspect a diffusion disorder and order an ______________________________ test. Results: Pa02 = 60, PaC02 = 39 Which observation is determinat to confirm you diagnosis of diffusion Impairment?

___________________________________________________

Patient C: Pa02 = 70, PC02 = 40 Pa02 = 74, PC02 = 39 Pa02 = 340, PC02 = 41

- at rest -during exercise - when breathing 100% 02

a. b.

Patient C has _____________________, 70 < 90 Adding Pa02 + PaC02 you have 70 + 40 = 110, this is less than ______, and you suspect __________________________ c. d. e. The PaC02 of the patient is 40 (normal) then this is not a case of _____________ You order an exercise test because you suspect a _________________________ You find that Pa02 has increased from 70 to 74 eliminating the diagnosis of diffusion disorder.

At this point you have eliminated: Hypoventilation (patient has normal paC02) Diffusion impairment (Pa02 increased during exercise) How can you differentiate between the other disease problems: 1. Venous shunt 2. Uneven ventilation

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Diagnostic test Diagnosis of shunt problem in a patient that presents low Pa02 Patient breaths 100% oxygen and if P02 < 600 If a patient whith any of the other three problems receives 100% oxygen the partial P02 Increases to 650 mmHg.

When the obove patient (patient C) received 100% oxygen the Pa02 increased only to 340 mmHg, then the patients problem is v-a mixture (shunt). How to determine the direction of the shunt Right to left shunt: low Pa02 in the artery. Left to right shunt:normal Pa02, high Pv02,high pressure in right Chamberts.

Diagnosis of a patient with uneven ventilation/perfusion Increased A-a D02 (increased difference in the alveolar and arterial P02 Could be uneven V or uneven Q ( VD alveolar). Is most commonly due to alveolar dead space volume. Normal A-a 02 difference is 5 to 10 mm Hg. The A-a difference should be of 30 When breathing 100% 02 and 10 when breathing Room air. When breathing 100% 02, for every 20 mm Hg of A a difference, there is 1% shunt.

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The Transport of Oxygen and Carbon Dioxide by the Blood

Copyright 2000 M. G. LEVITZKY

I. Transport of O2 by the blood A. Amount of O2 consumed at rest 250-300 ml/min. B. 1. Physical dissolved O2 in the blood 100 ml of plasma at 37C contains 0.003 ml O2/mmHg PO2. Normal arterial blood with a PO2 of 100 mmHg contains only 0.3 ml O2/100 ml blood.

C.

Chemical combination of O2 with the Hemoglobin (Hb). Approximately 15 g of Hb is present in each 100 ml of blood (15 g/dl) and each gram of Hb has the capacity to carry 1.39 ml of O2. 1. O2 carrying capacity of Hb = 1.39 ml O2/gm Hb. That is, if the Hb were maximally combined with O2 (fully saturated , the blood could maximally carry 20.4 ml/dl or 20.4 ml of O2 per 100 ml of blood (15 g Hb/dl x 1.39 ml/g of Hb = 20.85 ml/dl) (100% O2 saturation at 250 mmHg PO2). Therefore a person with the "normal" 15 gm Hb per 100 ml blood has a Hb O2 carrying capacity of 20.1 ml O2/100 ml blood a. % Hb saturation = % O2 saturation of Hb

2.

b. PO2 vs % Hb saturation. Under normal circumstances PO2 of the plasma determines the amount of O2 that combines with Hb. HbO2. Special properties of the reaction Hb +O2 Rapid and reversible: Half time is 0.01 sec or less.

3.

The oxyhemoglobin dissociation curve: a. The curve is sigmoid-shaped because hemoglobin molecule has four subunits. Each Hb molecule can carry four O2 molecules. The interaction of each one of the subunits with the O2 facilitates the successive combination of O2 with the next subunits. Similarly each dissociation facilitates the next. This S-shape is extremely important physiologically. b. At high PO2 values, large changes can occur in the PO2 value without significantly altering the % HbO2 saturation, while at low PO2 values, small changes in PO2 cause large changes in the % HbO2 saturation. c. In the lungs, the flat portion of the curve assures that the blood will be nearly fully oxygenated even in the situation in which the alveolar PO2 decreased to a value as low as 60 mmHg. At the tissue level, on the other hand, large amounts of O2 can be released by the blood into the tissue with small changes in the PO2 value (increased slope zone).

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The reaction rate is influenced by pH, PCO2 and temperature. D. Physiologic consequences of the oxyhemoglobin dissociation curve. 1. a. O2 loading - pulmonary capillaries Relatively flat. This means that Hb will remain highly saturated with O2 (and therefore have a high O content) at fairly low PO2's. (e.g. at a PO2 of 100 mmHg Hb is 97.4% saturated; at a PO of 70 mmHg Hb is still 94.1% saturated). This is of great value to a person at altitude or a patient with respiratory disease. It also means that PO2 reflects the respiratory state better than Hb saturation. pH and PCO2: decreased pH and increased PCO2 can decrease the loading of O2 (the Bohr effect). Also increased temperature can decrease O2 loading. Other factors interfering with O2 loading: Carbon monoxide - displaces oxygen from hemoglobin ++ +++ Methemoglobinemia Fe Fe (doesn't combine with O2) Anemia - decreased Hb O2 unloading - tissue capillaries Curve is very steep between 40 and 10 mmHg, which is in the range of metabolically active tissues. (at a PO2 of 40 mmHg, Hb is 75% saturated; At a PO2 of 20 mmHg, Hb is 32% saturated). At metabolically active tissues the pH is lower, the PCO2 is higher, the temperature is higher, and the 2,3 DPG levels (increased in anaerobic metabolism) are higher. These shift the HbO2 dissociation curve to the right and assist in unloading O2. They cause the mixed venous HbO2 dissociation curve to shift to the right. E. F. II. Myoglobin: High affinity for O2 - can store O2. Cyanosis: More than 5 gms deoxy Hb/100 ml arterial blood. Transport of CO2 by the blood: A. B. Amount produced at rest: 200-250 ml/min Physical solution: 1. CO2 is 20 X more soluble in plasma than is O2. Therefore about 5-10% of total CO2 transported is physically dissolved.
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C.

Carbamino CO2: About 5-10% of CO2 is transported as carbamino compounds. Deoxyhemoglobin forms more carbamino compounds than oxyhemoglobin. Conversion into bicarbonate (HCO3 ): About 80-90% of CO2 is transported as bicarbonate. Role of hemoglobin in CO2 transport: 1. 2. 3. 4. Deoxy Hb is a better H acceptor than Oxy Hb. That is, deoxy Hb is a weaker acid. Therefore: H+ + HbO2 H+Hb + O2 Therefore deoxy Hb can accept the H+ produced by CO2 + H2O H2CO3 H+ + HCO3-, allowing CO2 to be transported as HCO. Oxyhemoglobin is a stronger acid than deoxyhemoglobin, so it allows less CO2 to be transported as bicarbonate. Oxyhemoglobin also forms less carbamino compounds than deoxyhemoglobin.
+ -

D. E.

F. CO2 dissociation curve of whole blood: 1. Relatively straight. 2. Oxyhemoglobin shifts curve to the right (Haldane effect).

From: West. Respiratory Physiology

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III.

Hypoxia Can Have Several Causes A. Hypoxia is tissue oxygen deficiency Brain is the most sensitive tissue to hypoxia: complete lack of oxygen can cause unconsciousness in 15 sec and irreversible damage within 2 min.

Type of Hypoxia Hypoxic Anemic Ischemic Histotoxic

O2 Uptake in Lungs Low Normal Normal Normal

Hemoglobin Circulation Normal Low Normal Normal Normal Normal Low Normal

Tissue O2 Utilization Normal Normal Normal Low

B.

Causes: Hypoxic: high altitude, pulmonary edema, hypoventilation, emphysema, collapsed lung Anemic: iron deficiency, hemoglobin mutations, carbon monoxide poisoning Ischemic: shock, heart failure, embolism Histotoxic: cyanide poisoning (inhibits mitochondria)

1. Carbon monoxide (CO) poisoning: CO binds to the same heme Fe atoms that O2 binds to CO displaces oxygen from hemoglobin because it has a 200X greater affinity for hemoglobin. Treatment for CO poisoning: move victim to fresh air. Breathing pure O2 can give faster removal of CO
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o o o

2. Cyanide poisoning: Cyanide inhibits the cytochrome oxidase enzyme of mitochondria Two step treatment for cyanide poisoning: 1) Give nitrites Nitrites convert some hemoglobin to methemoglobin. Methemoglobin pulls cyanide away from mitochondria. 2) Give thiosulfate. Thiosulfate converts the cyanide to less poisonous thiocyanate.

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