chemical control of respiration

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Need for chemical regulatory mechanism? Maintenance of alveolar p CO 2 at constant level Combat the effect of excess H + in the body Raising pO 2 if it falls to potentially lethal level 2

Respiratory chemoreceptors:

Respiratory chemoreceptors Three types of respiratory chemoreceptors Peripheral chemoreceptor Medullary or central chemoreceptors 3

Peripheral chemoreceptors:

Peripheral chemoreceptors Carotid and aortic bodies Discovered by Heymans C and Neil E in 1930. C arotid body near the carotid bifurcation on each side, and usually two or more aortic bodies near the arch of the aorta. These chemoreceptors increase their firing rate in response to increased arterial pCO2, decreased arterial PO2, or decreased arterial pH. C arotid and aortic body ( glomus ) contains islands of two types of cells, type I and type II cells, surrounded by fenestrated sinusoidal capillaries 4

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Figure 1 Figure 2 Fig 1-Position of aortic and carotid bodies. Fig 2 and fig 3-Organization of carotid body 5

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Mechanism of neurotransmitter release by type 1 cells Image courtesy-http://www.colorado.edu/intphys/Class/IPHY3430-200/015breathing.htm 6

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Stimulus for activation of peripheral receptors Hypoxia- decrease in arterial pO 2 V ascular stasis- amount of O 2 delivered to receptors is decreased Asphyxia- lack of O 2 plus CO 2 excess Drugs- cyanide, nicotine etc 7

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Why are these receptors not activated in anaemia and carbon monoxide poisoning ??? 8

Central chemoreceptor:

Central chemoreceptor Also known as medullary chemoreceptor Located on the ventral surface of medulla near VRG. Stimulated by the H + concentration of CSF and brain interstitial fluid. Magnitude of stimulation is directly proportional to H+ concentration ,which increases linearly with arterial pCO 2. G ets inhibited by anaesthesia , cyanide and sleep. 9

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Rostral (R) and caudal (C) chemosensitive areas on the ventral surface of the medulla. 10

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Representation of the central chemoreceptor showing its relationship to carbon dioxide (CO2), hydrogen (H+), and bicarbonate (HCO3–) ions in the arterial blood and cerebrospinal fluid (CSF). HCO 3 - pH pCO 2 HCO 3 - 7.33 44 22 7.4 40 24 11

Chemical factors affecting respiration:

Chemical factors affecting respiration Effect of Hypoxia. Effect of CO 2 Effect of H + concentration 12

Effect of hypoxia on respiration:

Effect of hypoxia on respiration Decrease in O 2 content of inspired air increases respiratory minute volume. The increase is slight when the IpO 2 is above 60 mm Hg and marked when the IpO 2 falls below 60 mm Hg. The red curve demonstrates the effect of different levels of arterial PO2 on alveolar ventilation, showing a sixfold increase in ventilation as the PO2 decreases from the normal level of 100 mm Hg to 20 mm Hg. Ref –Guyton and Hall physiology 13

Effect of CO2 respiration:

Effect of CO 2 respiration The arterial PCO2 is normally maintained at 40 mm Hg. If arterial PCO2 rises as a result of increased tissue metabolism, ventilation is stimulated and the rate of pulmonary excretion of CO2 increases until the arterial PCO2 falls to normal. T his feedback mechanism keeps CO2 excretion and production in balance. There occurs an essentially linear relationship between respiratory minute volume and pCO 2 14

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When the PCO2 of the inspired gas is close to the alveolar PCO2, elimination of CO2 becomes difficult. When the CO2 content of the inspired gas is more than 7%, the alveolar and arterial PCO2 begin to rise abruptly in spite of hyperventilation. Figure depicts responses of normal subjects to inhaling O2 and approximately 2, 4, and 6% CO2. The increase in respiratory minute volume is due to an increase in both the depth and rate of respiration. Ref- Ganong review of medical physiology 15

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The resultant accumulation of CO2 in the body ( hypercapnia ) depresses the central nervous system, including the respiratory center , and produces headache, confusion, and eventually coma (CO2 narcosis). CO 2 primarily acts on central chemoreceptors but when central chemoreceptors are depressed by anaesthesia stimulation of peripheral chemoreceptors occur. 16

Effect of H+ concentration on respiration:

Effect of H + concentration on respiration H + normally cannot act through modification of central chemoreceptors. Acidosis (increase H + concentration in blood) produces marked respiratory stimulation causing hyperventilation Alkalosis (decrease H + concentration in blood) depresses respiratory centre and causes hypoventilation. 17

Interaction of chemical factors in regulating respiration:

Interaction of chemical factors in regulating respiration Interaction of CO 2 and O 2. Ventilation at various alveolar PO2 values when PCO2 is held constant at 49,44, or 37 mm Hg. (Data from Loeschke HH and Gertz KH.) 18

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Interaction of CO 2 and H +. The stimulatory effects of H+ and CO2 on respiration appear to be additive . In meatabolic acidosis the same amount of respiratory stimulation is produced by lower arterial pCO2 levels. The CO2 response curve shifts 0.8 mm Hg to the left for each nanomole rise in arterial H+. 19

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