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Gas transport in the Blood

Respiratory Regulation

III. Gas transport in the Blood


1. Transport forms of oxygen and carbon dioxide in the blood

Transport forms: physical dissolution (elementary substance O2, CO2) and chemical constitution (HbO2, HCO-3);

Systemic arterial and pulmonary venous blood are high in oxygen and low in carbon dioxide; Systemic venous and pulmonary arterial blood are high in carbon dioxide and low in oxygen.

Gas composition of arterial and venous blood

O2 exchange between the alveoli and blood and O2 transport


Movement of carbon dioxide and oxygen between the alveolar air and the blood and between the blood and peripheral tissue depends upon concentration gradients for these gases. As can be seen in this figure, the gradients favor the movement of oxygen from alveolar air to the tissue and movement of carbon dioxide from the tissue to alveolar air.
Venous blood Po2=40 mmHg Pco2=46 mmHg

CO2 exchange between the tissue cells and blood and CO2 transport
Movement of carbon dioxide and oxygen between the alveolar air and the blood and between the blood and peripheral tissue depends upon concentration gradients for these gases. As can be seen in this figure, the gradients favor the movement of oxygen from alveolar air to the tissue and movement of carbon dioxide from the tissue to alveolar air.

2. Oxygen transport in the blood


Oxygen is carried in two forms: dissolved (1.5%) and bound to hemoglobin (98.5%). Dissolved oxygen is inadequate to meet the bodys needs. Hemoglobin greatly increases the bloods oxygen-carrying capacity. Three terms describe the amount of oxygen in the blood: capacity, saturation, content. Oxygen binding to hemoglobin is influenced by pH, carbon dioxide, 2,3-diphosphoglycerate (2,3-DPG), and temperature. Carbon monoxide decreases the bloods oxygen content and capacity.

Oxygen transport in the blood


Physical dissolved form is secondary (1.5%).

Oxygen transport in the blood


Chemical combined form is dominating (98.5%).

Oxygen transport in the blood under the low Po2 in the blood

Structure of Hemoglobin
Hemoglobin (Hb) enables the blood to carry large quantities of oxygen. Hb consists of a heme, an iron-prophyrin, bound to a globin molecule, a large polypeptide chain. Four hemeglobin complexes combine to form the whole Hb molecule. There are 4 different globin molecules that vary slightly in amino acid composition and are designated alpha, beta, gamma, and delta chains. The most common form is Hb A, which consists of 2 alpha and 2 beta chains. Oxygen binds to the iron atoms in Hb and because the molecule contains 4 iron atoms, 4 oxygen molecules can be bound.

Fe2+

(1) Characteristic of Hb combining with O2

Reaction: fast, reversible, no enzyme catalysis, influenced by PO2. After Fe ion combined with O2, Fe ion is still Fe2+, so it is oxygenation rather than oxidization; Absorbing ability different made by response of different Hb to various spectrum. Ability of HbO2 absorbing shortwave spectrum (e.g. blue light) is stronger; Ability of HHb absorbing long wave spectrum (e.g. red light) is stronger; Blood color is related to Hb content, quality, arterial blood: bright red; venous blood: prunosus Cyanosis: when reduced Hb (HHb) in the body surface capillary bed blood is more than 5 g /100 ml, skin and mucosa display violaceous color.

O2+ Hb

PO2 PO2
HbO2

Three terms are used to describe the amount of oxygen in the blood
Oxygen content refers to the total amount of oxygen in the blood, that is, the sum of the amount dissolved plus the amount bound to hemoglobin (Hb). Oxygen capacity is the maximum amount of oxygen that can combine with Hb. It is determined by exposing blood to a very high Po2 and calculating the amount bound to Hb after subtracting the amount dissolved. The oxygen capacity is determined by the amount of Hb in the blood and by the ability of Hb to bind oxygen. Oxygen saturation * is the proportion of the total number of oxygen binding sites that are occupied. It is determined by the Po2 and the ability of Hb to bind oxygen, but not by the amount of Hb present in the blood. Oxygen saturation = Oxygen content / Oxygen capacity 100%

100
% Hemoglobin Saturation

20

Arterial Po2 Venous Po2


50 Oxygen Combined With Hb Oxygen Dissolved In Blood 0 0 10

50
Po2 (mm Hg)

100

Oxygen is present in the blood in a dissolved form and is bound to Hb. The partial pressure of oxygen determines how much is in each form. Much more oxygen is bound to Hb at any partial pressure than is dissolved.

Oxygen Content (mL/100 mL blood)

Oxygen dissociation curve or named O2-Hb binding curve

Oxygen dissociation curve


Notice that at normal arterial Po2 (100 mm Hg), Hb is over 95% saturated and that even at normal venous Po2 (40 mm Hg) it is still 75% saturated. Because of Hb, 100 mL of blood contain approximately 19 mL of O2 at arterial Po2 and about 14 mL at venous Po2 . This means that 5 mL of O2 were delivered to the tissue by 100 mL of blood because of Hb, more than 10 times the amount present in the dissolved form (0.3 mL).

Shape like Reversed S Style

Oxygen dissociation curve

Embryo and adult have some different percent O2 saturation of hemoglobin

Reason Why?

(3) Influencing factors of oxygen dissociation curve


Effect of pH on oxygen dissociation curve

pH decrease results in curve right shift which means that Hb releases more O2 to tissue cells for use.

Effect of Pco2 on oxygen dissociation curve


Bohr effectpH or PCO2 increase Hb releasing O2 (affinity)

Pco2 increase results in curve right shift which means that Hb releases more O2 to tissue cells for use.

Effect of temperature on oxygen dissociation curve

Temperature increase results in curve right shift which means that Hb releases more O2 to tissue cells for use.

Effect of 2,3-DPG (2,3-diphosphoglycerate) on oxygen dissociation curve

2,3-DPG increase results in curve right shift which means that Hb releases more O2 to tissue cells for use.

Carbon monoxide decreases the bloods oxygen content and capacity


Inhalation of carbon monoxide (CO) has several effects on oxygen transport by the blood. The affinity of CO for Hb is 240 times that for oxygen, so very small amounts of CO will occupy a large number of the oxygen binding sites. This effectively reduces the oxygen capacity of Hb. Because of this, Hb becomes saturated with oxygen at very low Po2 values, values that are less than those in venous blood. This means that little if any oxygen will be released for tissue use. The net effect is that at normal alveolar Po2 oxygen content and capacity of blood is greatly reduced even though Hb is saturated and the amount of dissolved oxygen is normal.

1Carbon dioxide transport by bicarbonate ion in the blood


CO2
Metabolism Tissue Fluid

blood plasma

CO2+ H2O CA HCO3- H+ Hb


(88%) (

RBC

Cl-

HHb

CA: carbonic anhydrase

Carbon dioxide transport by bicarbonate ion in the blood

Co2 or O2 Content (mL/100 mL blood)

2Comparison of dissociation curve of CO2 and O2 *


60 Carbon Dioxide

Venous Pco2 30 Arterial Pco2

Oxygen

0
0 50 Pco2 or Po2 (mm Hg) 100

The blood carries much more carbon dioxide than oxygen

Blood carbon dioxide Content (Volume%)

(3) Effect of O2 On CO2 dissociation curve *

Haldane effectO2 combining with Hb induces CO2 release, and HHb easily combines with CO2.

Pco2 (kPa)

4Interrelationship between O2 and CO2 in Transport by Blood


Just as CO2 alters O2 binding to Hb (Bohr effect), O2 alters CO2 binding (Haldane effect). As the Po2 increases, less CO2 can bind to Hb. This interrelationship between O2 and CO2 binding to Hb facilitates gas exchange with Hb both in the lungs and in the tissue. In the lungs, Po2 is high, which reduces CO2 binding to Hb, facilitating release into alveolar air. In the tissue Po2 is low, which increases CO2 binding to Hb, facilitating its removal from the tissue. As described in the previous section (Oxygen Transport in the blood) changes in Pco2 facilitate oxygen binding to Hb in an appropriate manner in tissue and lung.

IV. Respiratory Regulation


1. Respiratory centers and formation of respiratory rhythm

Control of breathing rhythm


Medulla and pons (bridge) form the integration center and contain neural elements that define the basic breathing rhythm (Using transecting method). In medulla, ventral respiratory group and the dorsal respiratory group that are responsible for establishing this rhythm. The basic rhythm is modulated by higher brain centers and by receptors located in the chest wall and lungs. Primary efferent output (depth and frequency of respiration ) is via the phrenic nerve to the diaphragm. Motor nerves that exit the spinal cord at several levels in the thorax innervate intercostal muscles. These muscles are activated when large volumes of air must be moved. Reflex of cough and sneeze is useful for defence in respiratory system.

Control of breathing rhythm


Rhythmicity unrhythmicity

The fourth ventricle

midbrain

Intact vagus nerve

Cut vagus nerve off

Different respiratory centers in brain stem regulate breathing rhythm


PC: Respiratory regulatory center; Bt C: Bts complex; VRG: ventral respiratory group; DRG: dorsal respiratory group; PBKF: Klliker-FuseNucleus; A/B/C/D: Different transect; NTS: nucleus tractus solitarius

Control of breathing rhythm

2. Reflex regulation of respiration

(1) Chemoreceptive reflex


Ventilation influenced by Po2 ,Pco2 , and pH ( [H+] )**

Two groups of chemoreceptors, medullary and peripheral, send afferent information to the medulla and influence the depth and rate of respiration. Medullary chemoreceptors are sensitive to pH and increase ventilation when pH falls ( [H+] ). Peripheral chemoreceptors are sensitive to pH, Po2 , and Pco2 with Pco2 being most effective. Sensitivity of the peripheral chemoreceptors is influenced by pH,. Po2 , and Pco2.

Medullary chemoreceptors
Chemical sensitive Area

Chemical sensitive Area influencing respiration Nuclei related respiration

The medullary chemoreceptors or central chemoreceptors are sensitive to pH. Since the blood-brain barrier is impermeable to H+, the medullary chemoreceptors do not directly sense the pH of the blood. However, CO2 can diffuse from the blood into the cerebral spinal fluid where it is converted to H+ and HCO3-.The hydrogen ions thus formed stimulate the medullary chemoreceptors.

Effects of plasma Pco2 on ventilation*

Effects of plasma Pco2 and H+ On ventilation *

Effects of plasma Po2 on ventilation*


2

The peripheral chemoreceptors: carotid and aortic bodies Ventilation

Notice, Serious anoxemia (hypoxia) will directly inhibit respiration

Ventilation influenced by Po2 ,Pco2, and pH ( [H+] )

The relative levels of pH, Po2 , and Pco2 influence the sensitivity of peripheral chemoreceptors to pH, Po2, or Pco2. When the Po2 or pH is low, the carotid body sensitivity to Pco2 is increased. Similarly, the carotid body sensitivity to oxygen is increased if the Pco2 is elevated. However, under some circumstances these interactions can be antagonistic. At high altitude Po2 falls because of the fall in atmospheric pressure. This stimulates ventilation but also reduces arterial Pco2 as carbon dioxide is blown off. The fall in Pco2 reduces the primary drive for ventilation and the sensitivity of the carotid body chemoreceptors to arterial oxygen. This leads to a further fall in arterial Po2 , enhancing oxygens stimulatory effect on ventilation. Ultimately, a steady state is reached between the stimulatory response to hypoxia (low oxygen) and the inhibitory effect of hypocapnia (low CO2).

(2) Other respiratory reflexes


Pulmonary stretch reflex: found in 1868 by Breuer and Hering.
Definition: pulmonary inflation or expansion result in inspiration inhibition turning into expiration and pulmonary collapse induces inspiration excitation (Hering-Breuer reflex). Pulmonary deflation reflex; Proprioceptive reflex of respiratory muscles;

Defensive respiratory reflexes: cough reflex and sneeze reflex.

Effects of different factors on respiration (Summary)

Changes in Ventilation

Pathological respiratory patterns


Coma

Cheyne-stokes breathing

Respiratory Depth Respiratory Center Respiratory Center Excitation

Pulmonary Blood

Encephalic high pressure

Biots breathing

Pathological periodical respiratory pattern

V. Role of the lungs in regulation of acid-base balance


Ventilatory Response to Acid-Base Changes
Because the CO2-bicarbonate buffer system plays a significant role in regulating pH, the lungs can alter arterial pH by changing arterial Pco2. Ventilation is increased in response to metabolic acidemia. Ventilation is decreased in response to metabolic alkalemia.

Role of the lungs in regulation of acid-base balance


The CO2-bicarbonate buffer system is the major way in which the body maintains arterial pH because the lungs regulate the CO2 level of the blood and the kidneys regulate the amount of bicarbonate (chapter4). CO2undergoes the following reaction in blood: CO2 + H2O H2CO3 H + + HCO3 pH=6.1+log ( [HCO3] / Pco2) {deriving from the HendersonHasselbalch equation} Normal blood values can be substituted for the various parameters. To convert the units of mm Hg for Pco2 to mEq/L, Pco2 is multiplied by 0.03. 7.4=6.1+log [24mEq/L/(0.0340 mm Hg)]=6.1+log 20/1 This relationship shows that as long as the ratio of bicarbonate to CO2 is 20:1,pH will be 7.4. The body adjusts the amounts of these two substances in order to maintain a normal pH. The lungs regulate the amount of CO2.

Role of the lungs in regulation of acid-base balance


Arterial H+ concentration can change for a variety of reasons. If the cause does not involve the lungs, it is said to be of metabolic origin. It is called metabolic acidosis if the pH decreases and metabolic alkalosis if the pH increases. If the lungs are the cause of the acid-base disturbance, the processes are called respiratory acidosis and respiratory alkalosis. An elevation in arterial H+ concentration and Pco2 will stimulate ventilation. The increase in ventilation will lower the Pco2 driving (reaction 1) further to the left helping to lower the H+ concentration. In addition, the kidneys will generate bicarbonate and secrete H+. An decrease in arterial H+ concentration and Pco2 will reduce ventilation allowing Pco2 to accumulate. This will generate additional H+ and help to return the pH to normal.

Altered ventilation causes acid-base changes


CO2 + H2O H2CO3 H + + HCO3 An inability of the lungs to remove CO2 results in respiratory acidemia. Inappropriate removal of CO2 by the lungs results in respiratory alkalemia.