Respiratory system: chemical and neuronal control mechanisms Flashcards
neural control of respiration
central rhythm generator in medulla (automatic)
Receptors in respiratory tract causing sneezing, coughing and hyperpnoea (incr rate and depth of breathing)
Nociceptors- detect noxious substances
Chemical control of respiration
central and peripheral chemoreceptors
Medulla control
ventral and dorsal respiratory group:
- discharge rhythmically
- efferent (output) neurones to respiratory motor nerves
- receives afferent input from periphery and pons
Pons control
Apneustic centre:
prolongs medullary centre firing
so depth of breathing incr
Pneumotaxic centre:
Inhibits apneustic centre
Controls rate of breathing
Pre-Botzinger complex
Region of ventral respiratory group
Spontaneous rhythmic discharge
stimulates rhythmic discharge of motor nerves, resulting in contraction of diaphragm
Key in regulation of breathing- without it there is a loss of regular rhythm and CO2 responsiveness
Are cortical/higher centres essential for breathing
No, but no longer voluntary control without them
Transection above pons
loss of voluntary control
Transection above medulla
loss of feedback regulation from pons (above medulla)
breathing continues
Transection of spinal cord
breathing abolished
Voluntary control of breathing
via cerebral cortex
sends signals direct to respiratory motor neurones
lung transplant
Motor innervation is to skeletal muscle, so ventilation carries on
Preservation of cough
from tracheal stimulation
But loss of cough stimulation in lower airway
Loss of Hering-Breuer reflex (prevents over inflation of the lung)
chemoreceptors
central and peripheral
Central (medullary)- H+, CO2
Peripheral- cartoid and aortic bodies. Primary peripheral signal is O2, but also input from H+
PO2
partial pressure of oxygen
PCO2
partial pressure of CO2
PaO2
partial pressure of arterial oxygen
PaCO2
Partial pressure of arterial CO2
PAO2
partial pressure alveolar oxygen
Central control of respiration
HCO3- and H+ don’t easily cross BB
CO2- uncharged- does cross BBB and dissociates in CSF
Hence CO2 larger influence on ventilation than pH
carbon dioxide effect
has little effect in stimulating neurones in the chemosensitive area, but does have a potent indirect effect by reacting with H2O in tissues to from H2CO3, dissociates into HCO3- and H+ ions, and H+ have direct effect on respiration
Hence whenever blood PCO2 incr, so does PCO2 of ISF in medulla and CSF, and H+ ions incr when CO2 reacts with water , so respiratory center activity incr by changes in blood CO2
How does H+ act on respiratory center
Stimulate central chemo receptors (CO2 can’t)
Incr ventilation
Reduction in blood PCO2
Regulation of CO2 during sustainable exercise
Ventilation incr prior ro rise in blood CO2- due to anticipatory stimulation in the higher CNS
Arterial PCO2 levels fall
As exercise goes on, more CO2 generated and arterial CO2 returns to normal
CO2 passes from muscles into venous blood and efficiently removed in the lung
Peripheral control respiration- O2
Fall in o2 stimulates glomus cells in cartoid and aortic bodies
Contains O2 sensitive K+ channels and dopamine
O2 falling sequence
O2 falls K+ channels close Depolarisation DA release which stimulates afferent fibres, signals to medulla Nerve firing increases at low PaO2
Doxapram
Closes K+ channels on glomus cell (cartoid body)
Glomus cell depolarises and sends afferent signals to medullary respiratory centre
used in respiratory failure
Caffeine
Non-specific CNS stimulation, including respiratory centre
bronchodilator
Acetazolamide
respiratory stimulant
carbonic anhydrase inhibitor
Stimulates respiration by creating mild metabolic acidosis via decr renal absorption of bicarbonate and hence reduced acid buffering
Cartoid bodies respond to decr in pH
Respiratory depressants?
Majority of drugs with depressant action on CNS
Why do we breathe?
O2 needed for respiration- krebs can’t proceed without regeneration of NAD+, ETC dependent on O2
ATP generated from respiration required for: active transport (maintaining ionic gradients, nutrient uptake), anabolic reactions, muscle contraction, phosphorylation of targets, precursor for cAMP
O2 also needed to pay O2 debt after bursts of anabolic metabolism
Pgas
barometric pressure x fraction of particular gas
PAO2
Alveolar pressure
O2 inspired - O2 consumed
How much O2 is consumed?
Estimate O2 consumption from CO2 in arterial blood
CO2 produced divided by O2 consumed is the respiratory quotient
PAO2 also equals
O2 inspired - (CO2 produced/RQ)
Uptake of oxygen in the pulmonary capillary
Alveolar O2 equilibrates with the blood in the capillaries
As blood in capillary gets oxygenated
How is oxygen transported
Most bound to haemoglobin
Binding is co-operative- 4 molecules of oxygen per haemoglobin molecule
Some O2 dissolved in blood
Myoglobin
O2 storage and transport in metabolically active cells
Skeletal and cardiac muscle
Doesn’t bind co-operatively- one O2 binding site
High affinity, affinity not affected by pH or CO2, so able to capture O2 released by Hb (when pH falls)
Myoglobin saturated by O2 at a much lower concentration
CO2 transport
Mainly as HCO3-
some as dissolved CO2
Some as carbamino haemoglobin (HbCO2)
what happens when CO2 diffuses tissues to plasma
Most enters RBC and converted to bicarbonate by carbonic anhydrase
When CO2 production increased (exercise/disease)
Fraction of CO2 increases relative to HCO3-
Passes into CSF and detection by central chemoreceptors
High PO2 in lungs causes the blood to release CO2
O2 binding to Hb makes it more acidic
Less formation of HbCO2
Excess H+ bind HCO3- to form H2CO3, Co2 released
Ventilation-Perfusion matching
For optimum GE ventilation must match blood perfusion
Mismatched in disease- reduced blood PO2
Hypoxaemia
Low O2 Shunting: unventilated alveoli ventilation-perfusion mismatch Diffusion abnormalities: thickened alveolar wall Hypoventilation (ventilation inadequate)
shunting
In shunting, venous blood enters the bloodstream without passing through functioning lung tissue. Often from blood flowing through unventilated portions of the lung
Hypercapnia
Incr CO2
Incr dead space: pulmonary embolus
Hypoventilation
Physiological response to low inspired O2
Incr ventilation: immediate, driven by peripheral chemosensors, not sustained
Pulmonary vasoconstriction: rapid, sustained, shunts blood away from poorly ventilated areas
Increased hematocrit: rbc cell fraction of blood incr, HIF activation (hypoxia inducible factors) which regulate oxygen-sensitive gene transcription and EPO production by kidneys (stimulate RBC production)
Acute mountain sickness
Flu-like, ahngover
Breathlessness
Hypoxic pulmonary vasoconstriction
Pulmonary and cerebral oedema (incr fluid in the lungs)
Chronic mountain sickness
Low PO2 cannot be matched by ventilation Incr EPO production in kidney Too high hematocrit, viscous blood Increased load on right heart Acetazolamide drug (carbonic anhydrase inhibitor) inhibits EPO production and incr ventilation
Genetic adaptions for high altitude populations
higher hematocrit
higher myoglobin levels
