PathoPhy LUNG Lec1 3 Gas exchange processes 1) Ventilation 2) Perfusion 3) Diffusion - Ventilation, the filling with the lung

and bronchi with fresh air must be properly match with perfusion for proper gas exchange. So Ventilation/Perfusion ratio is change, subject may have problem with gas exchange.

1) Ventilation
- Tidal volume(volume of fresh air which we use to filled our lung during every quiet inspiration) = 500 ml. - The Minute ration of breathing is 12. This means minutes ventilation is about 6L - We use to represent minutes ventilation - The minutes ventilation has 2 component: Part of this component is use to filled airway, and not use for gases exchange. The rest features, small brochiole, alveoli, are use for gases exchange - Within this 500 ml, which enter our respiratory system, during every average inspiration: 150 ml ~ Anatomy Dead Space: air that is use to filled airway (not use for gas exchange) 350 ml ~ Alveolar Ventilation : air reach alveoli (use for gas exchange) - Part of Tidal Volume, which is not used for gases exchange, is called Dead Space/ wasting ventilation. There are 2 type of Dead Space, Anatomy and Physiology. As this dead space is relate to anatomy of our respiratory system, so air that goes toward alveoli first, must pass through trachea and we call this Anatomy Dead Space. http://en.wikipedia.org/wiki/Dead_space Physiological Dead Space is equal to the Anatomy Dead Space + Alveolar Dead Space. -> Alveolar dead space is the area in the alveoli that does get air to be exchanged, but there is not enough blood flowing through the capillaries for exchange to be effective. It is normally veery small (less than 5ml) in healthy people. It can increase dramatically in some Lung Disease. - Alveolar Ventilation: means part of fresh air which is use in Gases exchange alveolar ventilation, the part of fresh air reach Alveoli, this is true in physiology sense. In pathology, alveoli is properly fed with fresh air, BUT, they had NO Perfusion. In this case, they also form Dead Space and not use for gas exchange. Within 6 L , 400ml is use for gases exchange. A= 4 L Always ventilation at the bottom of the lung are much more higher then the top of the lung due to its property.

At the end of Expiration, Alveoli at the top of the lung are little bit expanded compare to bottom. Curve of compliance:

It is defined: V /P [Voluem changes which occurs when pressure is change of 1 unit] so if Alveoli at the bottom which are totally close, with little low pressure, we change the pressure in the region of one unit, volume expand much more in comparison with the same effect at the top. Due to gravity, alvioli at the top initially, are little bit expanded in compare to bottom. [imagine in ventilation, 2 ballones: 1st which is totally collapse initially are easy to fill. The the 2nd ballone are already slightly expanded, and it would be harder for us to expanded it more due to its already posses pressure]

EXTRA READDING!!!!!!!!!!!!!!!!!!!!

Lung volumes
From Wikipedia, the free encyclopedia

Lung Volumes
Lung volumes refer to physical differences in lung volume, while lung capacities represent different combinations of lung volumes, usually in relation to respiration and exhalation.

The average pair of human lungs can hold about 6 liters of air, but only a small amount of this capacity is used during normal breathing. Breathing mechanism in mammals is called "tidal breathing". Tidal breathing means that air goes into the lungs the same way that it comes out.

Factors affecting lung volume

Several factors affect lung volumes, some that can be controlled and some that can not. These factors include: Larger volumes males taller people non-smokers athletes Smaller volumes females shorter people smokers non-athletes

people living at high altitudes people living at low altitudes A person who is born and lives at sea level will develop a slightly smaller lung capacity than a person who spends their life at a high altitude. This is because the atmosphere is less dense at higher altitude, and therefore, the same volume of air contains fewer molecules of all gases, including oxygen. In response to higher altitude, the body's diffusing capacity increases in order to be able to process more air. When someone living at or near sea level travels to locations at high altitudes (eg. the Andes, Denver, Colorado, Tibet, the Himalayas, etc.) s/he can develop a condition called altitude sickness because their lungs cannot respirate sufficiently in the thinner air.

Measurement and values

These values vary with the age and height of the person; the values that follow are for a 70 kg (154 lb), average-sized adult male:

Measurement

Value

Calculation

Description

Total lung capacity (TLC)

= 6.0 L

The volume of gas contained in the lung at the end of = IRV + TV + ERV + maximal inspiration. The total volume of the lung (i.e.: RV the volume of air in the lungs after maximum inspiration). The amount of air that can be forced out of the lungs after a maximal inspiration. Emphasis on completeness of expiration. The maximum volume of air that can be voluntarily moved in and out of the respiratory system. The amount of air that can be maximally forced out of the lungs after a maximal inspiration. Emphasis on speed. The amount of air breathed in or out during normal respiration. The volume of air an individual is normally breathing in and out. The amount of air left in the lungs after a maximal exhalation. The amount of air that is always in the lungs and can never be expired (i.e.: the amount of air that stays in the lungs after maximum expiration). The amount of additional air that can be breathed out after the end expiratory level of normal breathing. (At the end of a normal breath, the lungs contain the residual volume plus the expiratory reserve volume, or around 2.4 litres. If one then goes on and exhales as much as possible, only the residual volume of 1.2 litres remains). The additional air that can be inhaled after a normal tidal breath in. The maximum volume of air that can be inspired in addition to the tidal volume. The amount of air left in the lungs after a tidal breath out. The amount of air that stays in the lungs during normal breathing.

Vital capacity (VC)

= 4.6 L

= IRV + TV + ERV

Forced vital capacity (FVC)

= 4.8 L

measured

Tidal volume (TV)

= 500 mL

measured

Residual volume (RV) = 1.2 L

measured

Expiratory reserve volume (ERV)

= 1.2 L

measured

Inspiratory reserve volume (IRV)

= 3.6 L

measured IRV=VC(TV+ERV)

Functional residual capacity (FRC)

= 2.4 L

= ERV + RV

Inspiratory capacity (IC)

= 4.1 L

= TV + IRV

The volume that can be inhaled after a tidal breatheout. The volume of the conducting airways. Measured with Fowler method.

Anatomical dead space = 150 mL

measured

Anatomical dead space is the gas in the conducting areas of the respiratory system, such as the mouth and trachea, where the air doesn't come to the alveoli of the lungs.

Physiologic dead volume

= 155 mL

The anatomic dead space plus the alveolar dead space.

The tidal volume, vital capacity, inspiratory capacity and expiratory reserve volume can be measured directly with a spirometer. Determination of the residual volume can be done by radiographic planemetry, body plethysmography, closed circuit dilution and nitrogen washout. These are the basic elements of a ventilatory pulmonary function test. The results (in particular FEV1/FVC and FRC) can be used to distinguish between restrictive and obstructive pulmonary diseases: Type restrictive diseases Examples pulmonary fibrosis Description FEV1/FVC

volumes are decreased

often in a normal range (0.8 - 1.0)

obstructive diseases

asthma or COPD

volumes are essentially often low (Asthma can reduce the normal but flow rates are ratio to 0.6, Emphysema can impeded reduce the ratio to 0.3 - 0.4)

2) Perfusion
- Q = pulmonary capillary blood flow. Often referred to as "perfusion". - Minute perfusion Q 5L -> this is actual cardiac output of right ventricle. -> this is also the same as cardiao output of left ventricle. When we compare perfusion again with at the top of the lung with the perfusion at the bottome, Perfusion is also Higher at the bottom due to gravity!!

Ventilation & Perfusion ratio: in perfect situation in the alvioli, Ventilatino/ perfusion = 1 this situation shows our alveoli has just enough fresh air for oxygenation of blood which perfuses our alveoli. However, the mean alveoli Ventilation / Perfusion ration = 0.8 * This mean our lung act as a whole are little bit under ventilated * If think about minute ventilation~6L, 4L reaches area of gases exchange, so minute alveolar ventilation ~ 4L. Minute Perfusion ~ 5 L. * Mean Ventilation / Perfusion = 4/ 5 ( VA / Q ) = 0.8 = a little more air is necessary for oxygenation of blood in 100%. Ventilation / Perfusion ratio lower than 1 means that blood is not oxidized in 100% in physiology. In physiology, 1% up to 3 % of blood is not properly oxygenized, and we called it Venous Admixture. Venous Admixture refers to venous blood which is actually added to proper venous (not oxygenated blood is added to arterial blood). Venous Admixture INCREASES during AGING. Venous Admixture is related to the problem of peroper matching ventilation perfusion. Both Ventilation & Perfusion are higher at the bottom of lung then top. * Ventilation/Perfusion RATIO is higher at the top of the lung then the bottom of lung. * if only compare ventilation or perfusion (not their ratio) it is higher at the bottom of the lung. * Why Ventilation/Perfusion RATIO is higher? Because both ventilation and perfusion changes according to location of lung BUT not proportionally.

* The graph shows that ventilation is higher at the bottom and decreases when moving upward to the top of the lung. * Blood flow also higher at the bottom in comparison to the top. * However, Blood flow changes much more in comparison to ventilation, so Ventilaion / Perfusion ratio is low at the bottom and Increases when moving toward top of the lung. So the Ratio is Very HIGH at the top. * In Physiology, at the bottom of the lung, the Ratio = 0.5 [lowest value] * In Physiology, at the top of the lung, the Ratio = 3.3 [Highest value] * These values means that: > always we talk about gases exchange, we must talk about ventilation unit (conpose of Alveoli & Capillary). > When ventilation perfusion is low ~0.5,it meaning much blood come to the unit in comparison to the fresh air. blood leaving this unit is not properly ventilated. > unit at the top of lung ~3.3. Mean lot of fresh air in comparison with blood coming to the unit. the blood leaving the unit is properly oxygenized. Venous Admixture has 2 component: * 1st is related to period with low ventilation / perfusion ration > related to the alveoli at the bottom > when we breath deeper, we can improve ventilation so the ventilation perfusion ration is better. The blood is better oxygenized nd * 2 component is Anatomy Shunt . > Blood has no contact with the fresh air. > Alveoli is not ventilated (or No ventilation = 0) > Alveoli is perfuse, but with no fresh air VA / Q = 0 (Ventilation / perfusion = 0) > This type of shunt is also called Alveolar Shunt, and we dont have this type of shunt In physiology. * Anatomy Shunt is different, - 1st component of anatomy shunt: > This is blood pump by Left Ventricle (Oxygenized blood) goes back to left heart without oxygenation. > in bronchial circulation, bronchial artery transport nutrient & O2 to bronchi, part of them have direct contact with pulmonary system. So the blood is drained from bronchi, directly to Left Ventricle. > if this blood is not oxygenized, it form Anatomy Shunt.

- 2nd component of anatomy shunt: > it is form by part of circulation of the heart. We have so called, Thebesian Veins, which drained blood from Myocardium directly to the Left Heart. > This Thebesian Veins is not oxygenized, so form Anatomy Shunt. Anatomy shunt is less important when in comparison with this blood coming from the bottom of our lung. Gfdac

VA / Q = 1 (perfect situation) VA / Q = 0 (Alveolar Shunt) VA / Q < 1 (is called Venous Admixture) Alveolar shunt is a special form of Venous Admixture Remember in physiology, we dont have blood that is shunting EXCEPT Anatomy Shunt. We may have Alveoli which are Ventilated, BUT not Perfused. Eg. Capillary are obstruct by thrombus, VA / Q = ( Q = 0). The air enter this unit is not use for gases exchange and form Alveolar Dead Space (Alveolar Wasting Ventilation). Summary: Venous Admixture ( VA / Q = 0) . If

ventilation of an alveolus was stopped but flow allowed to continue, the PO and PCO of the alveolar air and end capillary blood would approachE that of mixed venous blood.
2 2

Alveolar Dead Space ( VA / Q = ) . If ventilation to an alveolus was continued while blood flow was halted, the PO2 and PCO2 of the alveolar air and end capillary blood would approached that of inspired air.

EXTRA READDING !!!!!!!!!!!!!!!!!!!!!!!!!!!!! In respiratory physiology, the ventilation/perfusion ratio (or V/Q ratio) is a measurement used to the efficiency and adequacy of the matching of two variables:

"V" - ventilation - the air which reaches the lungs "Q" - perfusion - the blood which reaches the lungs

A normal value is approximately 0.8. Because the lung is centered vertically around the heart, part of the lung is superior to the heart, and part is inferior. This has a major impact on the V/Q ratio:

apex of lung - higher base of lung - lower

The V/Q ratio can be measured with a ventilation/perfusion scan. An area with no ventilation (and thus a V/Q of zero) is termed "dead space" An area with no perfusion (and thus a V/Q of infinitiy) is termed Shunt (medical)|shunt]] http://en.wikipedia.org/wiki/Ventilation/perfusion_ratio

Normal V (ventilation) is 4 L of air per minute. Normal Q (perfusion) is 5L of blood per minute. o So Normal V/Q ratio is 4/5 or 0.8. When the V/Q is higher than 0.8, it means ventilation exceeds perfusion. When the V/Q is < 0.8, there is a VQ mismatch caused by poor ventilation.

http://www.rnceus.com/abgs/abgvq.html EXTRA READDING!!!!!!!!!!!!!!!!!

SHUNTS AND VENOUS ADMIXTURE Shunt is an overused word in pulmonary physiology and often means different things to different people. In its simplest definition, a shunt occurs whenever one thing bypasses another. In the lungs, a shunt can be thought of as an extreme form of venous admixture, i.e., a mixing of totally unventilated, unoxygenated blood with ventilated, oxygenated blood.*

Venous admixture can occur in one of three situations, only two of which are traditionally called "shunt." 1. An anatomic shunt occurs when blood bypasses the lungs through an anatomic channel, such as from the right to the left ventricle through a ventricular septal defect or from a branch of the pulmonary artery directly to a pulmonary vein. 2. A physiologic shunt occurs when a portion of the cardiac output goes through the regular pulmonary vasculature without coming into any contact with alveolar air. There is no abnormal connection between the blood vessels; rather, there is a severe redistribution of pulmonary blood flow. Physiologic shunting is often seen in conditions such as pulmonary edema, pneumonia, and lobar atelectasis. 3. Low ventilationperfusion ratios occur when there is relatively more blood in the pulmonary capillary than can be fully oxygenated by the alveolar air. Although blood flow is to some extent redistributed, the blood is still exposed to some alveolar air. Low V/Q ratios account for most cases of hypoxemia seen clinically. In terms of its effect on oxygenation, a physiologic shunt is not different from an anatomic shunt. In both, some unoxygenated blood bypasses the alveoli and mixes with oxygenated blood. Although both types of shunt represent venous admixture, they differ in one important aspect from venous admixture that occurs from low V/Q ratios. Since shunted blood contacts no air, increasing the fraction of inspired oxygen (FIO2) will not improve oxygenation (except by adding more dissolved oxygen to the normally oxygenated blood). In contrast, oxygenation of the blood from low V/Q areas will definitely be improved by increasing FIO2 because blood in low V/Q units is in contact with some air. Increasing the FIO2 should eventually denitrogenate the alveolar air in the low V/Q units and completely oxygenate the blood that serves these units; 100% oxygen should accomplish this exchange completely. Administration of 100% oxygen was recommended in the past to determine whether hypoxemia was from low V/Q areas or from a shunt. It is now known that 100% oxygen can cause shunting by converting areas of low V/Q to 0 V/Q. This conversion happens when the pure oxygen in the poorly ventilated alveoli is fully absorbed by the capillary blood and the alveoli collapse. Wellventilated alveoli (normal or high V/Q) are anatomically larger, and their collapse is less likely. Even if 100% oxygen gave an accurate measure of the percent shunt, the calculation would not ordinarily affect therapy. (Shunts and their calculation are discussed further in Chapter 11.)

http://www.lakesidepress.com/pulmonary/books/physiology/chap5_3.htm

3) Diffusion
- It is passive transport (without energy) - it is related to special amount of special gases which is transported - it is related to the Pressure difference of the gas in 2 compartment. - Diffusability: how easy gases pass through barrier and the structure of the gas. - 3rd parameter is related to the Area of gases exchange. Eg alveoli is destroyed, area is lower, and subject will have problem with gas exchange. - In physiology, 2 gases are exchange, O2 & CO2. - pressure of CO2 in venous blood coming to the lung is 46mmHg. PvCO2=46mmHg - pressure of O2 in venous blood is 40 mmHg. PvO2 = 40 mmHg.

- Partial Pressure of O2 in Alveolar = 100 mmHg PAO2 = 100mmHg - mean atmosphere pressure of gases at sea level = 760 mmHg. only 21% of atmosphere gases are O2 the rest consist other gases 760 x 21% = 160 mmHg = O2 pressure in atmosphere at sea level - when air enter our respiratory system, Eg upper respiratory part, Mosture is added to the air. - This 21% is called Fraction of Oxygen in Inspired air (FIO2): FIO2 = 0.21 - when we want to know O2 pressure in inspired air: Barometric Pressure 47(moisture which is added to the air) FIO2~21% Pressure in Inspired Air (PIO2) = (PB-47) x FIO2 At sea level & breath with Normal air: (PIO2) = (760 47) x 0.21 = 150 mmHg = Partial pressure of O2 in air which enter the alveoli due gas exchange, fresh air is coming from outside into alveoli, CO2 also coming to alveoli from the capillary. More CO2 coming , less O2 in the alveoli PIO2 is lower by the pressure of CO2 coming to the alveoli from the capillary. Partial Pressure of O2 in the alveoli: Ratio of O2 &CO2 PCO2 (PAO2) = PIO2 which are exchange R( respiratory quotient = 0.8) every respiratory 40 cycle: = 150 0.8 200[CO2]/250[O2]= = 100 mmHg 0.8 = mean O2 in the alveoli the mean of O2 in venous blood is 40 mmHg. Initially, pressure difference of O2 when diffused start is 60 mmHg NOTE: * Respiratory Quotient is some how related to Metabolic Quotient (the % of CO2 which is exchange for O2 at the tissue level). * So when diet is changed, eg. Highly diet, This quotientbecause less CO2 is produced. * when at Hard CO2 diet, more is produce & quotient is * The mean in Physiology of this R = 0.8 end point of diffusion through the IDEAL alveoli unit is 100 mmHg. Alveoli form open compartment with the air, so little bit lower O2 is compensated by the air from outside constantly. In Reality, the end point of diffusion through the REAL LIFE alveoli unit is slightly LOWER due to Venous Admixture. - If we want to know if our lung properly transfer O2, we can calculate a special parameter.

- This parameter is called: Alveolar-Arterial Pressure Gradient for the Oxygen. - The Proper name is: Alveolar-Arterial Pressure Difference for the Oxygen. - P(A-a)O2 = PAO2 PaO2 = 5 15 mmHg (increase during Aging!! Eg, up to 30 mmHg) - Alveolar-Arterial pressure Difference always exist due to Venous Admixture. - now we combine all equation that we discuss so far and calculate PAO2: PCO 2 PAO2 = PIO2 R ( respirator y quotient = 0.8) PCO 2 = (PB-47) x FIO2 R ( respirator y quotient = 0.8) = (equation 2) - in this equation, partial pressure of CO2 (PCO2) is the most important determinant of O2 pressure in the alveoli. - At sea level, PB ~ Constant (but in High Altitude, PB will change ). - in Normal Air: FIO2 ~ 0.21 (this value changes when subject is breathing with Air Supplement Eg. 40% Oxygen or 100% pure Oxygen) - Conclusion: PIO2 = 150 mmHg (more or less constant under the following condition * at sea level * breathing under atmosphere air) - In atmosphere, PCO2 = 0 CO2 does not enter alveoli with fresh air. - CO2 enter alveoli from the blood. - In alveoli, mean PACO2 = 40 mmHg - In venous blood, mean PvCO2 = 46 mmHg - so pressure difference between alveoli & Venous blood for CO2:P(A-V)CO2 = 6 mmHg (very low) - PAO2 = 100 mmHg ; PVO2 = 40 mmHg ; P(A-V)O2 = 60 mmHg - although Pressure difference of CO2 between Alveoli & Vein is 10 times lower then the Pressure difference of O2 between Alveoli & Vein, CO2 still diffuse much easier in comparison with O2.through the alveolar blood barrier. CO2 diffusability is much higher (20 times higher)!!! - This is why subject my have Hypoxemia WITHOUT Hypercapmia!!! due to High diffusibility of CO2!!! - Hypoxia = low oxygen in the tissue - Hypoxemia = low oxygen in the blood Hypoxia(low O2 in tissue) may be present WITHOUT Hypoxemia (low O2 in Blood) !!!! think about Heart, ischemic heart disease refer to Hypoxia in the heart (low O2 in Myocardium). 99% subject with ischemic heart disease have NORMAL O2 in blood!!! Hypoxia(low O2 in tissue) may be present in subject WITH Hypoxemia (low O2 in Blood) !!!! this is call Hypoxemic Hypoxia subject may have low O2 in tissue, blood which is coming is not properly oxygenized. But subject may have Normal oxygenized Hemoglobin and still he may have Hypoxia. This is called Anemic Hypoxia Eg in anemia, ParteryO2 = normal~high as a compensated feature, BUT, Hypoxia may be present due to LOW Haemoglobine, as in this case, the unit of blood transport less O2.

 Subject may have so call Circulatory Hypoxia. This is problem with O2 in the tissue in subject with ABNORMAL circulation Eg Heart Failure. Problem with proper blood flow We may have Histotoxic Hypoxia. In this case, circulatory system is ok, normal level of haemoglobin with normal level of O2 in blood, BUT tissue are not able to utilize the O2 Eg Cyanid Poison - Hypoxia MAY NOT be relate to problem in Respiratory system - Hypoxemia is ALWAYS relate to the problem in Respiratory system. - due to equation PAO2 = PIO2 PCO 2 : R ( respirator y quotient = 0.8)

Hypercapmia (CO2) ALWAYS exist WITH Hypoxemia (O2in Blood )!!! when breathing in normal air at sea level, it is 100% O2 in alveoli, and the end point of diffusion is also 100% O2 in the blood subject has high CO2, it lowers O2 in alveoli, eg 60 %, and the end point of diffusion is also 60 % O2 in the blood. - Hypoxemia (O2) MAY be present WITHOUT Hypercapemia (CO2)!!!