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