Lecture 12: Mechanism of Oxygen Carriage in the Blood - Medical Physiology PDF

شعار قسم الفسيولوجى.jpg  [ ] **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** ***O~2~ Carria...

شعار قسم الفسيولوجى.jpg  [ ] **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** ***O~2~ 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. - O~2~ 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 37^o^C, 3ml O~2~ 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 O~2~ requirement. - However, dissolved O~2~ determine the major pathway (direction of diffusion of O~2~) for transport of O~2~ 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%)]*** - - - - - - So 1L of blood containing 150g Hb can transport 200 ml. *[Compare this value with that of dissolved form ]* - **[O~2~ saturation]**: The percentage of total oxygen-binding sites on hemoglobin that are actually occupied by oxygen, also called the saturation of peripheral oxygen. - **O~2~ 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. - It's the relationship between the O~2~ tension (PO~2~) and % HbO~2~ saturation. It describes how the oxygen saturation of hemoglobin varies with the Po2 in the blood - The reaction between Hb and O~2~ 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.* - The intermediates compounds (Hb~4~O~4~ & Hb~4~O~6~ ) are responsible for the S shaped. If these compounds aren't formed and Hb~4~O~8~ is formed directly the curve would be straight line. - Binding of O~2~ to Hb is cooperative such that the binding of each O~2~ molecule to the Hb tetramer facilitates the binding of the next - So, the combination of the 1^st^ heam with O~2~ ↑ the affinity of the 2^nd^ heam for O~2~ and oxygenation of the 2^nd^ ↑ affinity of the 3^rd^ heam for O~2~ and so on. - Hb~4~ + O~2~ → Hb~4~O~2~ - Hb~4~O~2~ + O~2~ → Hb~4~O~4~ - Hb~4~O~4~ + O~2~ → Hb~4~O~6~ - Hb~4~O~6~ + O~2~ → Hb~4~O~8~  - 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.** - At 100 mmHg O~2~ tension, the Hb is 98 % saturated. - At 80 mmHg O~2~ tension, the Hb is 95 %saturated. - At 60 mmHg.O~2~ 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 Po~2~ hardly changes]* - ***[Note :]*** Even a small fall in blood *Po~2~ causes a* large unloading of O*~2~.* - At O~2~ tension = 40 mmHg, the Hb saturation is75 %. So, Hb saturation decreases by [**20 %**] (95% - 75 %). - Significance: During muscular exercise, PO~2~ 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 O~2~ delivered to tissues as they need more amount of O~2~ due to ↑ the activity of them. ***Factors affecting O~2~ D curve**:* *[Factors shifting to the right]:* It means the affinity of Hb to O~2~ is decreased OR more release of O~2~ from the Hb, caused by: 1-↑ temperature 2- ↑CO~2~ 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 O~2~ is increased) OR more bind of O~2~ 1-↓ temperature 2- ↓ CO~2~ 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 O~2~. The production of 2, 3-DPG is raised during hypoxic conditions, the  Ques of the graph.png ***[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, CO~2~ diffuses (Why ?) from blood into the alveoli, this ↓the blood PCO~2~ so ↓ H+ concentration. - This leads to shift to left → More binding of O~2~ 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 CO~2~ amount released and acids are produced.In addition, temperature of the muscle rises from 2-3C. All these factors cause shift the O~2~ hemoglobin dissociation curve to right which allows more release of O~2~ to the muscle~.~ *[1-Fetal haemoglobin (HbF]*) *has a raised affinity for O~2~* - 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 O~2~ than haemoglobin and does not demonstrate cooperativity in its binding of O~2~ - It can combine with one molecule of O~2\.~ and does not demonstrate cooperativity in its binding of O~2~ - The curve is rectangular hyperbola (remains horizontal till very low O~2~ tension then suddenly descends vertically ). - ***[So it acts as store of O~2~]*** to be used by muscle where O~2~ tension becomes very low in tissues (as in severe exercise or hypoxic conditions), and also allows O~2~ to be delivered to cells when muscle is contracted and perfusion reduced. *[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 O~2~ So~,~ Once Hb combines with CO, it can not combine with O~2\.~ 2- The Hb CO shift the O dissociation curve of the remaining oxy Hbg to the left. - The Hb CO breaks down very slowly. - 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 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 O~2~ 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 O~2~, normal % saturation of Hbg. Caused by decreased blood flow through the tissues ,May be : 1- Generalized (congestive heart failure) 2- Localized (Cold). **4- Histotoxic Hypoxia** - O~2~ 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.* - 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.