Physiology of Respiration (Lecture 12) PDF

Prof. Marwa Abd Elaziz Physiology of Respiration Lecture 12: Mechanism of Oxygen carriage in the blood Code: RRS-209 By...

Prof. Marwa Abd Elaziz Physiology of Respiration Lecture 12: Mechanism of Oxygen carriage in the blood Code: RRS-209 By Prof. Marwa Abd Elaziz Ahmed Professor of Medical Physiology Faculty of Medicine Assiut University Learning Objective : Knowledge:  Know how the oxygen is carried by the blood.  Define O2 content, O2 saturation, O2 utilization.  Describe the O2 dissociation curve and the physiological significance of the curve.  Know the causes of failure of oxygen transport and cyanosis.  Explain myoglobin dissociation curve, fetal Hbg. Intellectual:  Explore the factors causes shifting of O2 dissociation curve.  Compare between types of hypoxia 0  Prof. Marwa Abd Elaziz Physiology of Respiration O2 Carriage by the blood  Oxygen is transported in the blood from the alveolar capillaries of the lungs (where blood is loaded with O2) to the peripheral capillaries in the tissues.  O2 is transported in blood in two distinct ways: 1- Bounded to heamoglobin (Hb) OR 2- Dissolved in solution in ICF and ECF fluids O 2 in Physical solution:  The amount of oxygen dissolved in the blood is proportional to its partial pressure (Henry’s law).  At 37oC, 3ml O2 is dissolved in each liter of arterial blood per mmHg. So there is 3 ml / liter. In whole blood volume = 3X5= 15 ml.  Resting O2 consumption is approximately (300L /min) So the physical form of O 2 can not support the body’s O2 requirement.  However, dissolved O2 determine the major pathway (direction of diffusion of O2) for transport of O2 across capillary walls to the cells.  So an additional form of O 2 transport is needed. Heamoglobin provides this transport. 2- Chemical combination with Hb (98.5%)  Hb contains 4 atoms of iron. Each atom combines with one molecule of O 2 = Hb4 O8 ( there are only four ‘ hooks ’ for O 2 per molecule)  O2 content : The amount of O2 that can be bound to hemoglobin (mL/dL blood) in a liter of arterial blood.  calculated as 1.34 mL O2/dL blood × [Hemoglobin].  As 1gm Hbg contains 1.34 ml O2 and every 100 ml blood contain 15 gram of Hb.  in arterial blood =1.34 X 15 =20.1ml O2/100 ml blood Venous blood contains 15 ml/100 ml blood.  So 1L of blood containing 150g Hb can transport 200 ml. Compare this value with that of dissolved form  O2 saturation: The percentage of total oxygen-binding sites on hemoglobin that are actually occupied by oxygen, also called the saturation of peripheral oxygen.  O2 utilization: Every 100 ml of arterial blood while passing in the tissues loses O 2 and changes to venous blood.  Every 100 ml of arterial blood loses 5ml (20-15gm) = (50 ml / liter) to the tissues. Coefficient O2 Utilization = Arterial O2 content - venous O2 content X 100 Arterial O2 content 1 Prof. Marwa Abd Elaziz Physiology of Respiration O2 Dissociation Curve  It’s the relationship between the O2 tension (PO2) and % HbO2 saturation. It describes how the oxygen saturation of hemoglobin varies with the Po2 in the blood  The reaction between Hb and O2 is both rapid and reversible.  It’s not linear but it’s S (sigmoid) shaped curve. The curve has a steep slope between 10 and 60 mmHg PO2 and a relatively flat portion (or plateau) between 60 and 100 mmHg PO2. Causes of the sigmoid shape:  The intermediates compounds (Hb4O4 & Hb4O6 ) are responsible for the S shaped. If these compounds aren’t formed and Hb4O8 is formed directly the curve would be straight line.  Binding of O2 to Hb is cooperative such that the binding of each O2 molecule to the Hb tetramer facilitates the binding of the next  So, the combination of the 1st heam with O2 ↑ the affinity of the 2nd heam for O2 and oxygenation of the 2nd ↑ affinity of the 3rd heam for O2 and so on. Hb4 + O2 → Hb4O2 Hb4O2 + O2 → Hb4O4 Hb4O4 + O2 → Hb4O6 Hb4O6 + O2 → Hb4O8  The major function of Hb is to load with O2 at the lungs and unload at the tissues. This function is carried out at the flat (loading region) part of the curve and at the steep unloading region. 2 Prof. Marwa Abd Elaziz Physiology of Respiration The physiological significance of the flat part (used at the lungs):  At 100 mmHg O2 tension, the Hb is 98 % saturated.  At 80 mmHg O2 tension, the Hb is 95 %saturated.  At 60 mmHg.O2 tension, the Hb is 90 % saturated. From the curve you can observe  Thus, despite the marked fall in alveolar Po 2 from 100 to 60 mm Hg, the Hbg saturation changed from (98%) to (90%) which is still within normal levels. Thus the tissue Po2 hardly changes The physiological significance of the flat part (used at the lungs):  Note : Even a small fall in blood Po2 causes a large unloading of O2.  At O2 tension = 40 mmHg, the Hb saturation is75 %. So, Hb saturation decreases by 20 % (95% - 75 %).  Significance: During muscular exercise, PO2 is ranged from 15 -30 mmHg. The Hb saturation is 35%. So, Hb saturation decreases by 60% (3 times the normal) (95- 35%). Which means that there is more O2 delivered to tissues as they need more amount of O2 due to ↑ the activity of them. 3  Prof. Marwa Abd Elaziz Physiology of Respiration Factors affecting O2 D curve: Factors shifting to the right: It means the affinity of Hb to O2 is decreased OR more release of O2 from the Hb, caused by: 1-↑ temperature 2- ↑CO2 concentration in the blood. 3- ↓ in PH of the blood = ↑ in H+ conc. 4- ↑ in concentration Of 2’3 Diphosphoglycerate ( DPG) Shifting to the left : (The affinity to O2 is increased) OR more bind of O2 1-↓ temperature 2- ↓ CO2 conc. In the blood. 3- ↑ in PH of the blood = ↓ in H+ conc. 4- ↓ in conc. Of 2’3 DPG. 4- Effect of 2,3 Diphosphoglycerate (2,3 DPG)  2,3-DPG is produced by erythrocytes during glycolysis, binds to Hb and reduces its affinity for O2. The production of 2, 3-DPG is raised during hypoxic conditions, the 4  Prof. Marwa Abd Elaziz Physiology of Respiration Significance of shift O2 D curve : 1-The Bohr Effect: It is the ↑ of O2 delivery to the tissues when CO2 and H+ shift the curve to the right. In the lungs:  As the blood passes in the lungs, CO2 diffuses (Why ?) from blood into the alveoli, this ↓the blood PCO2 so ↓ H+ concentration.  This leads to shift to left → More binding of O2 to Hb so oxygenation of the blood occurs In tissues:  When blood reaches the tissues , the CO2 diffuse from the tissues to the blood , so PCO2↑ so shift the curve to the right which cause more release of O2 to the tissue. 2- In muscular exercise :  There are high CO2 amount released and acids are produced.In addition, temperature of the muscle rises from 2-3C. All these factors cause shift the O2 hemoglobin dissociation curve to right which allows more release of O 2 to the muscle. Variant types of HB 1-Fetal haemoglobin (HbF) has a raised affinity for O2  Compared with adult haemoglobin. This allows an increase in oxygen uptake in the placenta. Therefore, although fetal arterial PO2 is lower than that in the air- breathing newborn, fetal hemoglobin allows adequate oxygen supply to the developing organs. 2- O2 D curve of myoglobin:  Is a form of haemoglobin expressed in striated muscle fibers. It has a much higher affinity for O2 than haemoglobin and does not demonstrate cooperativity in its binding of O2  It can combine with one molecule of O2. and does not demonstrate cooperativity in its binding of O2  The curve is rectangular hyperbola (remains horizontal till very low O2 tension then suddenly descends vertically ).  So it acts as store of O2 to be used by muscle where O2 tension becomes very low in tissues (as in severe exercise or hypoxic conditions), and also allows O2 to be delivered to cells when muscle is contracted and perfusion reduced. 5  Prof. Marwa Abd Elaziz Physiology of Respiration 3- Carbon monoxide:  It is a colorless, odorless gas that is a product of the incomplete combustion of fuel (e.g. gasoline).  It is a common cause of sickness and death due to poisoning,  It has extremely high affinity— 210 times that of oxygen—for the oxygen-binding sites in hemoglobin. For this reason, it reduces the amount of oxygen that combines with hemoglobin in pulmonary capillaries  It also exerts a second deleterious effect as it shift the oxygen-hemoglobin dissociation curve to the left, thus decreasing the unloading of oxygen from hemoglobin in the tissues.  Why Carbon monoxide is highly toxic gas?  1-The affinity of Hbg to CO is 210 times its affinity for O2 So, Once Hb combines with CO, it can not combine with O2. 2- The Hb CO shift the O dissociation curve of the remaining oxy Hbg to the left.  The Hb CO breaks down very slowly. Describe effects (Polycythemia, Anemia and CO on Hb concentration) Hypoxia (Failure of O2 transport)  The term for a lack of oxygen in the tissues is hypoxia. Lack of O 2 in arterial blood is termed hypoxaemia. Total absence of O 2 is anoxia.  Types of hypoxia : 1- Hypoxic hypoxia 2- Anaemic hypoxia 3- Stagnant hypoxia 4- Histotoxic hypoxia 6  Prof. Marwa Abd Elaziz Physiology of Respiration 1- Hypoxic Hypoxia:  In this type , there is ↓ PO2 of arterial blood, The Hbg saturation with O2 is decreased and there is ↓ PO2 of venous blood.  When there is decrease in arterial PO2 which goes to the tissues, there will be decrease in average PO2 in capillary blood so the rate of O diffusion to the tissues is ↓ which causes symptoms of O2 lack. Causes: 1- High altitude 2- Breathing low % of O2. 3- Shallow rapid breathing ( may results from pulmonary congestion )because there is : a- ↑ ratio of the volume of the DS to Tidal air. b- Greater number of alveoli will not be distensible. 4- Depression of respiratory centers: as in morphine poisoning. 5-Diseases of the lung : may cause hypoxia but with different mechanisms: a- By diffusion impairment : due to thickened pulmonary membrane as in pneumonia, pulmonary oedema b- By decreasing surface area : emphysema. c- Difficulty in breathing : Bronchial asthma in which there is increased resistance to air flow in the respiratory passages. 6- Shunting of venous blood. 2- Anaemic Hypoxia  In this type; Normal Pa O2 ,normal % saturation of Hb.  Arterial O2 content is ↓because of ↓ Hb amount which is capable of carrying O2.  During passage of the blood in the tissues, a fewer number of RBCs. passes through the tissues and, so the O2 tension decreased in the venous blood and then it decreased in the capillary blood leading to production of the hypoxic symptoms. Causes: 1- All types of anemia. 2- Carbon monoxide (CO) poisoning. 3- Stagnant Hypoxia In this type: Normal Pa O2, normal % saturation of Hbg. Caused by decreased blood flow through the tissues ,May be : 1- Generalized (congestive heart failure) 2- Localized (Cold). 7  Prof. Marwa Abd Elaziz Physiology of Respiration 4- Histotoxic Hypoxia  O2 released from Hbg is transported to the cell by the cytochrome system.  Histotoxic Hypoxia results from inactivation of metabolic enzymes which facilitate this transport.These enzymes are Cytochrome dehydrogenase and cytochrome oxidase  Cyanide can block the cytochrome oxidase & Alcohol block the cytochrome dehydrogenase. Cyanosis  Means the blue discoloration of the skin and mucous membrane, due to excessive amounts of deoxygenated Hbg in skin vessels.  Threshold of cyanosis:  Appears when the arterial blood contains more than 5 grams deoxygenated Hbg in each deciliter of blood.  Causes: 1-Alveolar hypoventilation: 2-Inadequate oxygenation: as in deficiency of O in atmosphere. 3- Diffusion impairment 4- Ventilation-perfusion mismatch 4- Right to left shunt. 5- Circulatory defect (generalized &localized) 6- Abnormal forms of Hb Central cyanosis:  Caused by reduced O2 saturation. Involves highly vascularized tissues such as lips and tongue and mucous membrane. Peripheral cyanosis:  Results from increased oxygen extraction from the peripheral blood resulting from sluggish movement of blood through capillary circulation.  Affects distal extremities Cyanosis occurs in moderate cold in exposed areas in normal individuals because there is arteriolar and venous constriction and there is slow blood flow in the capillaries & more oxygen is removed from Hg. Cyanosis is not present in: Sever cold: the drop in temperature causes shift to the left and the O2 uptake of the cold tissues is reduced. 8