Chemical Regulation

1. Chemical Regulation Dr B.Kalpana

2. At the end of class students should be able to: 1.Explain the role of respiratory chemoreceptors on ventilation. 2. Explain the effect of hypoxia, hypercapnia and acidosis on ventilation. 3. What are the causes and compensatory mechanism in respiratory acidosis and alkalosis.

3. Significance of chemical regulation • Helps in Homeostasis of • PO2 • PCO2 & • H+ ions • Achieved through Chemoreceptors

4. Chemical Regulation of Respiration It is the basic mechanism for regulation of breathing. -Increase arterial PCO2 -Increase arterial H+ ion -Decrease arterial PO2 Stimulate respiratory chemoreceptors Increase activity of respiratory center and Increase pulmonary ventilation.

5. Chemoreceptors-Peripheral Site: Aortic bodies: over aortic arch Carotid bodies: at bifurcation of each common carotid artery. Innervation: Carotid bodies: glossopharyngeal nerve Aortic bodies: vagus nerve

6. 2- Peripheral Chemoreceptor PathwayPeripheral Chemoreceptors Peripheral chemoreceptors are the only sensors detecting a fall in PO2

9. Peripheral chemoreceptors –stimulated Hypoxia Vascular stasis Asphyxia Drugs Increase in plasma K+ levels

10. The receptors are not stimulated -anaemia and Carbon-monoxide poisoning.

11. Central Chemoreceptors Site: Located bilaterally just beneath central surface of medulla. Stimulus: 1- Response to H+ ion ( primary stimulus). 2- Response to PCO2. 3- Response to PO2.

12. Central Chemoreceptors Pathway • Monitor the pH associated with CO2 levels within the CSF in the fourth ventricle. • The chemoreceptors synapse directly with the respiratory centers. • Most sensitive to change in PCO2 ,H+ conc., but not to PO2

14. Role of Hypoxia: Hypoxia acts mainly through peripheral chemoreceptors Stimulation is slight when PO2 in mm Hg declines from 100 mmHg up to 60 mmHg; below 60 mmHg it is marked Reason – Stimulatory effect of hypoxia will manifest only when it is strong enough to override the inhibitory effect of 1. fall in H+ ions (as Hb is weaker acid than HbO2) 2. low PCO2 (due to hyperventilation) on respiration which is possible only PO2 below of 60 mm Hg.

15. The carotid & aortic bodies are sensitive to fall in PO2, an increase in PCO2 or H+ concentration • They maximally stimulated when PO2 decreases below 50-60mmHg • They detect changes in dissolved O2 but not in the O2 that is bound to Hb (e.g. in anaemia there is normal PO2 but reduced content of O2 bound to Hb)

16. Hypoxia inhibits K + channels by: • Loss of oxygen from heme-containing protein • Increase in cAMP • Inhibits mitochondrial oxidase

17. Role of CO2: Increase in alveolar PCO2 increases arterial PCO2 Increase in arterial PCO2 stimulates peripheral chemoreceptors by increasing CO2 in glomus cell-stimulates ventilation. Hyperventilation-decreases alveolar PCO2 When inhalation of gas contain >7% of CO2,the arterial PCO2 rises in spite of hyperventilation -- Leads to hypercapnia – which depresses CNS, produce headache, confusion & even coma (CO2 narcosis)

19. Effect of Hypoxia & Hypercapnia: When alveolar PCO2 is above normal, there is an inverse relationship between ventilation & PO2 at any level. Hypoxia–increase the sensitivity of ventilation response to hypercapnia.

22. Role of H+ ions: Stimulatory effects of H+ ions & CO2 on ventilation is additive. Acidosis inhibits acid-extruding transporters .It increases H+ in the cell. It inhibits K+ channels. Acidosis-hyperventilation Alkalosis –hypoventilation These effects are mediated by peripheral chemoreceptors.

23. Chemoreceptors modify ventilation to maintain normal CO2, O2, and pH levels • PCO2 is most crucial because of its effects on blood pH • H2O + CO2 H2CO3 H+ + HCO3- • H2O + CO2 H2CO3 • H2CO3 H+ + HCO3- • Hyperventilation causes low CO2 (hypocapnia) • Hypoventilation causes high CO2 (hypercapnia)

24. Integrated responses to hypoxia, hypercapnia and acidosis

25. Acid-base balance • CO2 + H2O = H2CO3 = HCO3- + H+ • Blood pH = 7.35- 7.45 • Hb can bind (and buffer) H+ • Respiratory acidosis: excess H+ due to CO2 retention (hypoventilation) • Respiratory alkalosis  loss of H+  due to loss of CO2 (hyperventilation)

26. Metabolic acidosis Decrease in HCO3- concentration in blood secondary to increase in H+ concentration. Causes Renal failure ,DM Compensatory mechanism increase in H+ concentration stimulate RC-fall in blood H+ concentration due to loss of CO2

27. Metabolic alkalosis Increase in HCO3- concentration in blood secondary to decrease in H+ concentration. Cause Loss of HCl from blood. Compensatory mechanism Fall in H+ concentration depress RC-increase in blood H+ concentration due to retentionofCO2

28. Respiratory acidosis caused by decreased pulmonary ventilation Causes • Emphysema and depression of RC Compensatory mechanism • Hypoventilation causes CO2 accumulation-increased ventilation-CO2 washout-restoring H+ concentration towards normal.

29. Respiratory alkalosis • caused by increased pulmonary ventilation • Causes • voluntary hyperventilation • High altitude • Compensatory mechanism • Hyperventilation causes CO2 washout- ventilation slows down-CO2 retained-restoring H+ concentration towards normal.

30. Summary

31. References • Comprehensive Textbook of Medical physiology (Vol 2 first edition) G K Pal • Text book of medical physiology (Vol 2 6 th edition) A K Jain • Text book of medical physiology (Twelfth edition) GUYTON and HALL AEJ

32. This was reviewed by the review committee on 5.1.19