Chemical control of respiration

1. Chemical control of respiration By,Dr.M.B.Bhat.

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

3. Chemo receptors • Two types • Peripheral chemoreceptors • Central chemoreceptors • Hypoxia stimulate respiration through peripheral chemoreceptor; but hypoxic direct effect on center is inhibition • Through central chemoreceptors PCO2 aids in determination of normal respiratory rhythm; since it is more sensitive to central than peripheral chemoreceptors • H+ ions has got stimulatory effect on both central & peripheral chemoreceptors

4. Peripheral chemoreceptors

5. Peripheral chemoreceptors • Location: Carotid body & Aortic body Nerve supply – (called as Buffer nerves) • For carotid body –Carotid sinus nerve (Herring nerve), a branch from Glossopharyngeal (IX) nerve • For aortic body – a branch from vagus (X) nerve

7. Stimulus for Peripheral chemoreceptors • Arterial blood level -- • Hypoxia (more potent) • Hypercapnea • Increased H+ ions (Decrease pH)

8. Carotid body weight – 2 mg Blood flow to carotid body – 0.04ml/min Equivalent to 2000 ml/min/100gm tissue Metabolic need of carotid body is supplied by dissolved oxygen itself So these receptors are stimulated, whenever O2 delivery per unit time is decreased O2 delivery per unit time depend upon Oxygen tension (PO2)

9. Factors decreasing O2 delivery per unit time & thereby stimulating these receptors • Low PO2 • Vascular stasis –leads to Low PO2 (which also increase PCO2 & H+ ions) • Cyanide (prevents utilization of O2) • Infusion of K+ ions • Sufficient dose of drugs –nicotine & lobeline • BP <70 mm Hg up to 40 mm Hg

10. Conditions not stimulating chemoreceptors • Anemia • CO poisoning • In both these conditions – • O2 content in the blood is decreased • But PO2 level in the blood is normal • Hence O2 delivery per unit time is not affected

11. Effect of removal of peripheral chemoreceptors • Ventilatory response to hypoxia is completely lost • Ventilatory response to Hypercapnea reduced by 30% • Ventilation at rest is not affected

12. Central chemoreceptors • Located on the ventral surface of medulla near inspiratory center (these receptors contain carbonic anhydrase enzyme) • Mechanism of stimulus – by H+ ion conc. In CSF; (these receptors are H+ ion sensitive receptors) • Normal stimulus – CO2 (As blood level H+ ions cannot cross the blood-brain barrier); CO2 which enter brain hydrated by CSF to form H2CO3, dissociates to give HCO3 & H+ ions –stimulates chemoreceptors • Effect: Stimulation of central chemoreceptors – stimulate inspiratory center located near by. • Significance – • Normally also have slight but definite ‘CO2 drive’ on respiratory center through these receptors • keeps the PCO2 level at 40 mm Hg • Also helps in the rhythmicity of respiration

14. Note – the threshold value for PCO2 on ventilation is below normal alveolar PCO2 level

15. Summary: 1. Role of CO2: As long as arterial PCO2 is elevated hyperventilation persists till to bring back PCO2 to normal As long as arterial PCO2 more; hyperventilation persists even with high arterial PO2 level 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)

16. 2. Role of Hypoxia: Hypoxia acts mainly through peripheral chemoreceptors Stimulation is slight when PO2 in mm Hg declines from 100 up to 60; below 60 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 onlywhen PO2 is below 60 mm Hg.

17. Effect of Hypoxia & Hypercapnia: When alveolar PCO2 is above normal, there is an inverse relationship between ventilation & PO2 at any level When alveolar PCO2 is below normal, the stimulatory hypoxic effect appears only below PO2 of 60 mm Hg When alveolar PO2 is held constant, there is linear relationship between ventilation & CO2 concentration. Hypoxia makes more sensitive to increases of arterial PCO2

18. 3. Role of H+ ions: Stimulatory effects of H+ ions & CO2 on ventilation is additive. Each nanomole rise of H+ ions is equivalent to rise of 0.8 mm Hg of CO2 About 40% of ventilatory response to CO2 is lost if H+ ions increase due to CO2, is prevented. (loss of H+ ions effect through peripheral chemoreceptors)

19. Role of respiration on acid-base balance: Hypoventilation –retention of CO2 –Respiratory acidosis Hyperventilation –wash out of CO2 – Respiratory alkalosis Metabolic acidosis – pronounced respiratory stimulation (Kussmaul’s breathing)—blow of CO2 –produce compensatory rise in blood pH. Metabolic alkalosis –Respiratory depression leads to accumulation of CO2 –decrease blood pH

20. Effect of hormone on respiration • Adrenaline – injection of adrenaline produce apnea • –not direct action on respiratory center • – but through baroreceptors due to increase BP • Thyroid hormone –stimulate both rate & depth of respiration (secondary due to its effect on metabolism) • Progesterone –directly stimulate respiration

21. Pulmonary arterial chemo-reflex • Similar to coronary chemo-reflex (Bezold-Jarisch reflex) • Stimulus – Injections of drugs such as serotonin, capsaicin, veratridine and related drugs into the pulmonary artery and so called pulmonary chemo reflex. • Afferent – ‘C’ fibers goes through vagal afferent • Center – Respiratory & CVS centers • Effect -- on respiration as well as CVS • On respiration --Apnea followed by rapid breathing, • On CVS -- bradycardia, and hypotension

22. Voluntary Breath holding • Time varies up to only few minutes • Breaking point – at which voluntary breath holding is no longer possible is due to –hypercapnia & hypoxia of blood. • Time can be prolonged – • By removal of peripheral chemoreceptors • Breathing 100% oxygen or hyperventilation before breath holding • Psychological factors

23. End Thank you