Respiratory physiology 2: Transport and regulation of respiratory gasses Flashcards
O2 is transported in the blood by it dissolving into plasma, why isn’t this sufficient?
How do we then meet our demands?
-*Protein-bound O2
The vast majority of O2 (98%) is transported bound to haemoglobin in erythrocytes
What is the structure and function of haemoglobin?
- Quaternary structure protein (1/3 of RBC weight)
- 4 globin proteins:
> mostly 2 β and 2 α chains> HbA - 4 hemes: a Fe2+ ion bound to a porphyrin ring
- ROLES: fully reversible binding to O2 and CO2 to allow for transport in the blood, buffering agent as it can bind and unbind H+ to ensure minimal changes in pH
What are the 2 confirmations of Hb?
- Tensed (T) state which has low affinity for O2
- Relaxed (R) state which has high affinity for O2
Why is the O2-Hb dissociation curve sigmoidal?
- At low pO2, Hb is in the T state which has low affinity for O2. >There is therefore a low probability for Hb to bind to an O2 molecule
- As the pO2 rises, the probability for O2 to bind to Hb increases
>When eventually an O2 binds to 1 Hb subunit, this induces a conformational change within that subunit - This conformational change in 1 Hb subunit pulls on the weak non-covalent salt bridges linking all the subunits together, increasing the probability that they break
- Disruption of the salt bridges causes all the other subunits of the Hb molecule to change to the relaxed (R) form
>In this form, the O2 binding site is more exposed, thus increasing the O2 affinity of Hb (x150) - Thus as the pO2 rises, more Hb molecules change from the low affinity T form, to the high affinity R form
> As this happens the affinity of the overall Hb population for O2 increases
> Thus for a given step increase in pO2, more O2 is bound to Hb and the gradient of the dissociation curve increases - At high pO2, affinity of Hb for O2 is maximal and all Hb is in the R form and all O2 binding sites on Hb are occupied (saturated)
> At this point Hb cannot bind any more O2 for any given step increase in pO2
Application:
- How is O2 loaded in pulmonary capillaries?
- How does Hb ensure that O2 is only delivered to metabolically active tissues?
- How is O2 unloaded at actively respiring tissues?
- What makes Hb an excellent reversible carrier?
1.PaO2 is “high” - Hb has high affinity for O2 → O2 rapidly and reversibly binds to Hb in erythrocytes
2.pO2 falls slowly → Hb still has high affinity →little O2 is released.
3.PO2 is “low” (PCO2 + [H+] are “high”)→ Some Hb switches
from high to low affinity form, triggering unloading of O2.
- Switch between high and low affinity
At rest/basic metabolic needs how much O2 to we need per min?
- 250Ml/min
How can more O2 be delivered to tissues with increased
metabolic demands (e.g. skeletal muscles during exercise)?
- Environmental changes in the capillaries supplying metabolically active tissues facilitate unloading of O2 from haemoglobin
> small increase in temperature, >increase in PCO2 level and >reduction in pH
- H+ and CO2 individually react with Hb (not at O2 binding site) causing a decrease in Hb affinity for O2
> This allows for increased O2 delivery in metabolically active tissues
-. This shows up as a right-sided shift in Hb-O2 dissociation curve
Why is ensuring efficient CO2 removal important?
-Maintain the pH of the blood.
>An increase in arterial pCO2 will cause a drop in arterial pH
Can CO2 dissolve directly into the blood?
-Yes :
>Limited solubility of CO2 limits the quantity of CO2 that is transported dissolved in the plasma and cytosol of erythrocyte
>Only 10%
Describe the 3 ways of CO2 transport from respiring tissues to the lungs.
How is CO2 released at the lungs?
- Decrease PCO2 ,
- Increase PO2 > diffuses into RBC binds with Hb at haem group
> O2 alters Hb shape slightly , reduces Hb affinity for CO2 and H+
» HALDANE EFFECT:
*CO2 dissociation curve shifts downwards > total blood CO2 content decreases
-The more O2 that binds to Hb the more CO2 and H+ unbinds
-The reduction in pH causes the reaction catalysed by carbonic anhydrase (CA) to reverse
- HCO3- enters RBC from plasma down conc gradient > makes CO2
- PCO2 increases pushing CO2 down partial pressure gradient from RBC into plasma into alveoli
-CO2 expired
What is the difference between total ventilation rate and alveolar ventilation rate?
What do neurones in the brain stem fire?
-Intrinsic periodic action potential firing
> subconscious & rhythmical coordinated activation of respiratory skeletal muscle
- What is ventilation controlled by?
- What does the respiratory centre consist of?
- What is the *medullary respiratory centre responsible for?
- What are the Pons responsible for?
- What else modules ventilation?
- Somatic nervous system
- Medulla + Pons
- Neurons in the respiratory centre in the medulla are essential for ventilation:
➢Dorsal Respiratory Group (DRG) neurons – active during normal inspiration
➢Ventral Respiratory Group (VRG) neurons – active during forced expiration and inspiration - Areas in pons modulates ventilation
- Sensory inputs to DRG and voluntary behaviours modulate ventilation
What factors stimulate/inhibit ?
-Voluntary behaviour
-Emotions
-Sensory input
> Sensory inputs
- Chemoreceptors (peripheral and central (medullary)) +
- Receptors in muscles and joints +
- Stretch receptors in lungs to limit overextension of lungs -
- Mechanoreceptors and irritant receptors -
- Where are Central chemoreceptors found?
- What does it respond to changes in?
- What are the central chemoreceptors responsible for?
- Medulla oblongata
- Respond to changes in arterial PCO2 via alteration in pH of the cerebrospinal fluid (CSF) - indirectly :
-HOW?
1.Dissolved CO2 diffuse through the blood-brain-
barrier (while blood H+ and HCO3- cannot)
2.Carbonic anhydrase in the CSF catalyses the formation of HCO3- and H+ from CO2 and H2O
3.H+ derived from this reaction increase the AP firing rate of chemosensitive neurons - Tonic ventilatory drive, meaning that they are always firing, and the firing rate changes according to amount of H+ detected
65-80% of the ventilatory response to changes in blood gases is mediated by central chemoreceptors in the medulla …> 10min for response tho
- Where are peripheral receptors found?
- What sensory neurons are they innervated by?
> Carotid bodies:
1. Bilaterally at the bifurcation of each common carotid artery
2.Afferent fibres of glossopharyngeal nerve (CN IX)
> Aortic bodies
1. Underside of the aortic arch
2.Afferent fibres of the vagus nerve (CN X)
What are some features of peripheral receptors?
- Small
- High metabolic rate
- Very high arterial blood flow
- Complex structures made of glomus cells, arterioles, sinusoids, afferent and efferent neurones
How do peripheral receptors respond to change?
- Glomus cells detect changes in arterial pO2
- Unknown receptor activated by decreased arterial pO2
- K+ channels close
- Depolarisation
- Opening of VG Ca2+ channels
- Increased Influx of Ca2+ in glomus cells
- Exocytosis of neurotransmitter
- Increased AP firing in sensory neurones
How is ventilation rate adjusted through negative feedback?
Long term adaptation to low pO2
-2 ADAPTATIONS
