Lecture 8- Chemical control of breathing: peripheral and central chemoreceptors Flashcards
respiratory control centre found
medulla pons
singals from the respiratory control centres are transported to the effectors which are
respiratory muscles and the diaphragm
sensors
peripheral cehmoreceptors
central chemoreceptors
pulmonary mechanoreceptors
Chemical control of ventilation
Automatic centres in the brainstem activate respiratory muscles rhythmically and subconsciously- set automatic rhythm for contraction of respiratory muscles- but need to be able to respond to changed need and production of PO2, PCO2, pH
-
Ventilation needs to accommodate several tasks
- Maintain adequate oxygen status
- Adjust respiration for changing metabolic status/ needs reflected y altered PO2, PCO2, pH – measure of H+
peripheral chemoreceptors sense
PO2, PCO2 and pH levels
central chemoreceptors
pH and pCO2
both peripheral and central chemoreceptors
- both send info to brain resp centre- resulting adjustments both in depth and frequency of ventilation as needed
where are the peripheral chemoreceptors found
carotid bodies and aortic bodies
Carotid bodies
- Glomus cells- sensors
- Located bifurcation common carotid arteries
- Don’t confuse with carotid sinus- baroreceptors
- Sensory enervation branch of CN IX
Aortic bodies
- Located in aortic arch
- Sensory enervation branch of CN X
both aortic and carotid bodies are primarily sensitive to
decreased arterial pO2 although high pCO2 (hypercapnia) and low pH (acidosis) also stimulates
- Hypoxaemia increases peripheral chemoreceptors sensitivity to acidosis and hypercapnia
- Rapid responders- first chemoreceptors to respond
Major function carotid & aortic bodies sense hypoxaemia & signal cells in the medulla to
increase ventilation
- If peripheral chemoreceptors sense low PO2 and high PCO2 they will feed back to the medulla resp centre to increase minute ventilation- leads to increase pO2 and decrease PCO2
But….. how does increasing minute ventilation compensate for acidosis (low pH- high protons?)
CO2 strongly influences blood pH- think bicarbonate buffer system
- Therefore if CO2 levels increase, H+ increases
- Conversely- decreasing CO2 will cause H+ decrease- so pH rises
where are Central chemoreceptors found
- Specialised neurons located on BRAIN side of the BBB i.e. located within the brain parenchyma and bathed in brain ECF which is separated from arterial blood by BBB
BBB=
endothelial cells of blood vessels in rain surrounded by pericytes and foot processes (end feet) of astrocytes to create a highly selective permeability barrier
central chemoreceptors sense
- increases in arterial PCO2 and much more slowly- decrease in arterial pH, but not arterial PO2
When blood-gas parameters are nearly normal central chemoreceptors are the x
primary source of feedback to the brainstem resp centres for needed adjustment- medulla
- If PCO2 increases suddenly then ventilation increases rapidly- augmenting minute ventilation
Location of central chemoreceptors
- Central chemoreceptors are an anatomical collection of neuronal chemoreceptors
- Located just beneath the ventral surface of the brainstems medulla
- Few hundred microns away from the brainstem resp centre
Central chemoreceptors- how do they sense changes PCO2 and pH
BBB separates central chemoreceptors in medulla from arterial blood
- BBB has a low permeability to ions such as H+ and HCO3-, but high permeability to small molecules like CO2
- CO2 diffuses into brain brain
extracellular fluid (BECF, also called Brain Interstitial fluid) bathing brain cells including Central Chemoreceptor Neuron Cells - CNS very limited HCO3- buffering capacity and therefore acidosis develops
- Even small decreases in pH raise the firing rate of the central chemoreceptor neurons thus increasing ventilation
- Many diseases may lead to chronic hypercapnia e.g.
emphysematous COPD
Central chemoreceptors and chronic hypercapnia
- If CO2 remains elevated, pH of CSF/BECF slowly recovers (i.e. increases) over 8-24hours- because choroid plexus increases active transport of HCO3- into CSF - bicarb buffers protons generated by increased CO2 are mopped up by HCO3- this CO2-induced acidosis gradually reduces- pH rises
- This transport represents CNS metabolic compensation to respiratory acidosis
- This adjustment also means that higher level of CO2 is needed to cause acidosis and thereby increase ventilation- thus CO2 drive for ventilation has been reset to a higher level
metabolic compensation from chronic hypercapnia
There is also metabolic compensation throughout the body for respiraotry acids- kidneys achieve by increasing blood bicarbonate through increased reabsorption- occurs over 3-5 days not hours
outline hypoxaemic dive
- chronic elevated PCO2 levels
- medullary chemorecepors become insensitive to high PCO2
- PCO2 increases, PO2 decreases
- no increase in resp
- marked decrease in O2 levels
- very low pO2 stimulates peripheral receptors
- inspiratory muscles srtimulated
- increased resp
- removed CO2/take in O2
- PCO2 decreases, PO2 increases
- respiration slows
summary of Chemical control ventilation
- Peripheral and central chemoreceptors form vital sensory arm sending signals to the automatic respiratory centres to adjust minute ventilation
- Acutely peripheral chemoreceptors most quick to respond – and only ones to respond to hypoxaemia – low PO2
- Both peripheral and central chemoreceptors respond to high PCO2 and low pH (acidosis)
- Hypoxaemia (low PO2.), Hypercapnia (high PCO2), and Acidosis (low pH) all cause anincrease in ventilation – which, (all being right with the world)
- Raises PO2
- Lowers PCO2
- Raises pH and normalised
- Correcting imbalance
- All three parameters very tightly regulated as maintenance of oxygenation and acid-base balance essential for functioning of all the enzymes in our body – below pH 7 enzymes denature! BUT we have a wider range of safe PO2. levels
Q1. A healthy 28 y/o woman climbing Kilimanjaro becomes hypoxaemic and increases her minute ventilation. How is this compensatory mechanism initiated?
a) Stimulation of the central chemoreceptors leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
b) Stimulation of the carotid bodies leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
c) Stimulation of the carotid sinus leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
d) Stimulation of the central chemoreceptors and carotid bodies leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
e) Stimulation of the carotid bodies and carotid sinus leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
B
The correct answer is B - Stimulation of the carotid bodies leads to afferent signals to the brainstem respiratory centres, which in turn act on respiratory muscles to increase respiratory rate and tidal volume
Q2. A morbidly obese (BMI>40) man comes to his GP complaining of chronic fatigue; his initial blood work is shown below:
The GP measures his respiratory rate and notes that it is normal. What is one of the mechanism that explains this normal respiratory rate in this patient?
a) Central chemoreceptors are not normally sensitive to elevated CO2 levels
b) Peripheral chemoreceptors are not normally sensitive to elevated CO2 levels
c) Chronic hypercapnia resets the sensitivity of the central chemoreceptors to elevated CO2 levels
d) Chronic hypoxaemia resets the sensitivity of the peripheral chemoreceptors to elevated CO2 levels
e) Metabolic acidosis does not stimulate the central or peripheral chemoreceptors
C
Chronic hypercapnia resets the sensitivity of the central chemoreceptors to elevated CO2 levels. This happens because the choroid plexus starts reabsorbing more bicarb which buffers the protons generated from the elevated CO2. -
– Remembering the equation
Q3. A 45 y/o man is admitted with pneumonia; his arterial blood gas (ABG) is shown below:
• ABG:
pH–7.48(7.35-7.45)
PCO2–4.0kPa(4.6-6)
PO2 – 6.6 kPa (>10.6) (NB 6.6 kPa = 50 mmHg)
HCO3 – 24 mmol/L (22-28)
Based on the graph at what approximate rate would you expect his carotid body nerve impulses to be firing?
a) 700impulses/second
b) 450impulses/second
c) 250impulses/second
d) 200impulses/second
e) 100impulses/second
The correct answer is B – approximately 450 impulses/second
Q4: A 14 y/o boy is brought to A&E by his father who states that his son has been losing weight, drinking large amounts of water, and urinating frequently, over the past several days. Now he is also complaining of malaise and generalised weakness. Physical exam reveals a boy who appears acutely unwell and who is breathing very rapidly and deeply. The physician suspects diabetic ketoacidosis and amongst other blood tests orders an Arterial Blood Gas (ABG); results are shown below:
pH – 7.20 (7.35-7.45)
PCO2 – 2.5 kPa (4.6-6)
PO2 – 14.1 kPa kPa (>10.6)
HCO3 – 18 mmol/L (22-28)
• What is the initial sequence of events that has led to the patient’s rapid and deep breathing (Kussmaul respiration) and partial compensation?
a) Acidosis induced stimulation of his central chemoreceptors followed by stimulation of his carotid bodies
b) Acidosis induced stimulation of his carotid bodies followed by decreased firing of his central chemoreceptors
c) Hypocapnia induced stimulation of his carotid bodies followed by stimulation of central chemoreceptors
d) Hypocapnia. induced stimulation of his central chemoreceptors followed by stimulation of his carotid bodies
The correct answer is B - Acidosis (caused by ketoacidosis) induced stimulation of his carotid and aortic bodies followed by decreased firing of central chemoreceptors – this is because initially his hypocapnia decreases the stimulation of the central chemoreceptors. Later, as protons cross the BBB the effects on Central chemoreceptors of a low pH AND a low CO2. means that the full hyper ventilatory drive that would occur with this level of acidosis if it were soley due to elevated CO2 is partially dampened – therefore there is not complete compensation of metabolic acidosis.
