CO2 Transport
• CO2 in blood – 4ml/dl
• Cl- shift*
CO2 Dissociation Curve
Regulation of Respiration
Regulation of Respiration
• Objective of ventilatory control:• Establish automatic rhythm for respiration contraction• Adjust this rhythm to accommodate varying
» Metabolic demands» Mechanical conditions» Non-ventilatory behaviours
• Arrangement of regulation• Central control (CNS centres, central chemoreceptors)• Peripheral chemoreceptors
Central Control of Breathing
• Medullary respiration centre• Located in RF
– DRG» Inspiration – RAMP signal» Input – X (PCR, mechanoR in lungs), XI (PCR)» Output – Phrenic N. to diaphram
– VRG» Inspiration & Expiration» Not active during normal, quiet breathing» Activated during exercise
• Apneustic centre• Located in lower pons
» Stimulates inspiration during deep & prolonged inspiratory gasp
• Pneumotaxic centre• Located in upper pons
» Inhibits inspiration – regulates inspiratory volume, RR
• Cerebral cortex» Voluntary control of respiration
Hering Breuer Reflex
• Stretch R in bronchi and bronchioles• Overstretching of lungs stimulates these R• Signals sent to DRG –
• Inhibition of RAMP occurs (pneumotaxic centre-like effect)
• Hering Breuer reflex checks OVERINFLATION of lung
Central CRs • Location:
– Ventral surface of medulla, – Near point of exit of CN IX & CN X – Only a short distance from the medullary inspiratory center – Affects the centre directly
• Central CR sensitive to: • pH of CSF (decrease in pH – increases RR)• CO2 crosses BBB >> easier than H+
• (CO2 + H2O ----- H+ + HCO3)
• Increase in CO2 & H+ ----- increases ventilation – decreases levels of CO2 & H+
• Role of CO2 in regulation of respiration is mainly acute (the H+ is adjusted within 1-2 days by kidneys!)
• O2 DOES NOT affect CCR*
CO2 affects Ventilation*,**
Acid–Base Balance affects Ventilation• Respiratory response in Metabolic Acidosis
– E.g due to accumulation of acid ketone bodies DM– Response:
» Pronounced respiratory stimulation (Kussmaul breathing)
» The hyperventilation decreases alveolar PCO2 ("blows off CO2")
» Thus produces a compensatory fall in blood [H+]
• Respiratory response in Metabolic Alkalosis– E.g: protracted vomiting with loss of HCl from body– Response:
» Ventilation is depressed » Arterial PCO 2 rises, raising the [H+] toward normal
Acid–Base Balance affects Ventilation
• Respiratory Acidosis– Can occur when Pco2 rises via:
» Direct inhibition of respiratory centres (sedatives, anesthetics)
» Weakening of respiratory muscles (polio, MS, ALS)» Decreased CO2 exchange in pulmonary blood (COPD)
– Renal adjustment of H+/HCO3- corrects for this
• Respiratory Alkalosis*– Can occur when Pco2 decreases via:
» Hypoxemia causes hyperventilation (pneumonia, high altitude)
» Direct ++ of resp. centers (salicylate poisoning)» Psychogenic
– Renal adjustment of H+/HCO3- corrects for this
Peripheral CRs
• Cells of PCR:– Type I (glomus) cell
• Is +++ by:– Decrease in Po2 (especially
drop in Po2 between 60-30 mmHg)
– Increase in Pco2 (generally not as imp as its effect on CCR; but its affect is 5 times more rapid on PCR than CCR – role in raising RR at exercise onset)
– Decrease in pH
– Type- II cell• Function: support
Peripheral CRs
• Blood flow to each carotid body is VERY high!!* – Hence O2 needs are met largely by dissolved O2 alone – Therefore, the receptors are NOT +++ in conditions such as
anemia or CO poisoning** – Powerful stimulation is also produced by cyanide, which
prevents O2 utilization at the tissue level – Infusion of K+ increases discharge rate in CR afferents
• Plasma K+ level is increased during exercise, the increase may contribute to exercise-induced hyperpnea.
Po2, Pco2, H+ Scenarios In Respiration Control
• Changing Po2 (Pco2 & H+ = constant)– Po2 below 100 mmHg profoundly influences respiration control
• Changing Po2 (Pco2 & H+ = fluctuating)– Decreasing Po2 increases RR– Increasing RR – increased CO2 blow-off – decreasing Pco2 – which
inhibits RR
• Acclimatization:– Decreased sensitivities of CNS resp. centres to CO2
Respiratory Response to Exercise
Respiratory Response to High Altitude