Control of Breathing

Which muscles are involved in inspiration?

External intercostals, diaphragm, parasternal intercostals, scalenes and sternocleidomastoid (need control)

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Which muscles are involved in expiration?

Internal intercostals, external abdominal oblique, internal abdominal oblique, transversus abdomins, rectus abdomins (need control)

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State the components on a spirometer trace

Inspiratory reserve volume, tidal volume, expiratory reserve volume, residual volume (vital capacity, functional residual capacity, total lung capacity)

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What are the two primary controls for the muscles?

Phrenic nerves and cervical/thoracic/lumbar/motor nerves (control frequency and amplitude)

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What are the two types of control for the muscles?

Neural control (brain stem/primary control centre, lung receptors, other inputs). Chemical control (response to pCO2, pO2 and pH, central chemoreceptors in the brain, peripheral chemoreceptors (aorta, bifurcations))

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Summarise the sensory receptors in the body (1)

Higher brain cortex (cerebral cortex, voluntary control over breathing). Other receptors e.g. pain and emotional stimuli acting through hypothalamus, respiratory centre (medulla/pons)

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Summarise the sensory receptors in the body (2)

Peripheral chemoreceptors (carotids, detect low O2, high CO2, high H+). Central chemoreceptors (respiratory centre, medulla, pons, detect low O2, high CO2, high H+). Stretch receptors in lungs, irritant receptors, receptors in joints/muscles

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Which receptors in inhibit respiration?

Stretch receptors in the lungs and irritant receptors

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Which receptors stimulate respiration?

Receptors in muscles and joints, central chemoreceptors, peripheral chemoreceptors

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Which receptors can inhibit or stimulate respiration?

Receptors in higher brain centres (cerebral cortex for voluntary control over breathing) and other receptors e.g. pain and emotional stimuli acting through hypothalamus

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Describe features of central chemoreceptors

Sensory neurone located within CNS (medulla), usually brain stem or hypothalamus. Responds to chemical stimuli. Enteroreceptor sensitive to concentration changes - variety of molecules in the blood or CSF

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Describe features of peripheral chemoreceptors

Sensory neurone located outside the CNS. Usually in blood vessel wall (e.g. aortic body, carotid body, juxtaglomerular apparatus) which responds to chemical stimuli. Enteoreceptor sensitive to concentration changes of molecules in blood/body fluids

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Describe features of neural control (1)

Involves inspiratory muscles, diaphragm and intercostal muscles. Nerve supply - motor outputs from phrenic and thoracic segmental nerves. Normal breathing (eupnoea) basic rhythm

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Describe features of neural control (2)

AP causes muscle contraction followed by a pause to allow relaxation of muscles. In forced expiration - abdominal muscles need to receive nerve stimulation. Respiratory basic rhythm generator (in medulla)

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Describe features of neural control (3)

Most cells in region show a discharge pattern synchronous with either inspiration (I neurones) or expiration (E neurones). Some cells discharge both inspiration and expiration (I-E neurones)

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Which section is the spinal cord is responsible for breathing?

C3 (breathing stopped when C3 is cut). If there was a cut below C5, breathing was ok but there was paralysis in the arms and legs. Cervical region sent information essential for breathing

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Describe features of the brain stem centres (1)

Consists of the mid brain, pons (neurones modulate ventilation) and medulla (respiratory neurone control, inspiration/expiration). Network spontaneously discharging neurones -> rhythmic pattern breathing

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Describe features of the brain stem centres (2)

Ventilation modulated by chemoreceptor-linked reflexes and by higher brain centres

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Outline respiratory control

Sensors (chemoreceptors, lung receptors). Central controller (pons/medulla). Effectors (respiratory muscles) - feedback to sensors

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Describe features of the medulla respiratory centres (1)

Neural activity cycles during quiet breathing (inspiration/expiration). 2 groups of neurones (dorsal respiratory group/back, ventral respiratory group/front). VRG (controls external intercostals), DRG (control external intercostals/diaphragm)

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Describe features of the medulla respiratory centres (2)

2 groups of neurones which generate APs (pacemaker activity). Dorsal respiratory nuclei (inspiration). Ventral respiratory nuclei (forced expiration)

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Describe features of the medulla respiratory centres (3)

DRG (nucleus tractus solitarius, primarily inspiratory neurones, ramp increase activity during inspiration then abrupt no activity). VRG (3 groups, Botzinger complex, nucleus abiguus, nucleus retroambiguus, inactive during quiet respiration)

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Describe features of the medulla respiratory centres (4)

Important during exercise and stress (both inspiration and expiration)

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Describe features of the medulla respiratory centres (5)

Both medulla groups have pacemaker activity. Combined activity DRG/VRG and interconnections (network) - basic rhythm generator for respiration

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Describe features of the medulla pattern generator

Respiratory neurones are connected and show reciprocal inhibition. Firing by inspiratory neurones inhibits activity of expiratory neurones. Respiratory muscles e.g. diaphragm, intercostals, abdominal muscles

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Describe features of the pons centre (1)

Medulla centres sends signals to and receives inputs from pons. 2 respiratory centres (pneumotaxic centre, apneustic centre). Receive input from rhythm generator in medulla and higher centres - hypothalamus and cerebral cortex

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Describe features of the pons centre (2)

Integrates inputs - over ride control of medulla centres

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Describe features of the pons centre (3)

Pneumotaxic centre (controls inspiratory volume and respiratory rate, inhibits DRG). Apneustic centre (prolongs ramp signal - controls depth inspiration, stimulates DRG)

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Describe features of voluntary control of respiration

Can over-ride brain stem respiratory centres. Mediated - motor neurones in cerebral cortex. Corticospinal tract - spinal motor neurones - respiratory muscles (directly by pass brainstem respiratory centres). Important if autonomic control defective

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Outline the pathway for neural control (1)

Cerebral cortex - hypothalamus (temperature). Emotion (limbic system, pneumotaxic centre) to rhythm generator. Pons, medulla. Lung receptors, chemoreceptors (terminate tractus solatarius, DRG). Spinal cord

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Outline the pathway for neural control (2)

Voluntary control via pyramidal tracts very important in rare disorders of brainstem - congenital central hypoventilation syndrome (Ondine's curse). Can bypass pathway and go straight to spinal cord

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Give examples of lung receptors

Pulmonary stretch receptors. Irritant receptors. J receptors. Bronchial C-fibres

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Describe features of the stretch receptors

Located in smooth muscle of bronchial walls. Detects stretching of airway wall. Nerve - afferent via vagus to DRG. Makes inspiration shorter/shallower. Allows expiration to occur (delays next inspiratory cycle)

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What is the Hering-Breuer inflation reflex?

Lung inflation - inhibits inspiration. Example of negative feedback on inspiratory neurones. Important when tidal volume is high >1 L e.g. during strong exercises

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Describe features of irritant receptors (1)

Located throughout airways between epithelial cells. Nerve - afferent vagus. Stimulated by irritant gases, smoke and dust, inflammation, rapid large inflation and deflations. Receptors in trachea lead to coughing

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Describe features of irritant receptors (2)

In bronchi can cause bronchial constrictions to remove irritant stimuli

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Describe features of irritant receptors (3)

Responsible for deep augmented breaths seen every 5-20 mins at rest (reserve slow collapse of lungs in quiet breathing). Action also stimulates surfactant release to help expand lungs

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Describe features of juxtapulmonary receptors (1)

Located in alveolar/bronchiolar walls, close to capillaries, normally dormant. Nerve - afferent via vagus nerve. Stimulated in pathological conditions (lung damage, detect increased alveolar wall fluid)

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Describe features of juxtapulmonary receptors (2)

(Due to oedema, pulmonary congestion, microembolisms or release of inflammatory mediators e.g. histamine). Rapid shallow breathing or apnoea (cessation breathing) and laryngeal constriction

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Describe features of juxtapulmonary receptors (2)

Also cause decrease in HR/BP to suppress metabolism (consequence of lung disease)

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Describe features of other receptors (1)

Upper airway receptors. Proprioceptors - joint receptors, muscle spindles and golgi tendon organs, detect load/shortening of respiratory accessory muscles, stimulate breathing (match exercise/joint movement to ventilation)

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Describe features of other receptors (2)

Arterial baroreceptors - pain and temperature, initial cessation then increased breathing

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Outline the chemical control of breathing

Tissue metabolism (CO2 production, O2 consumption, H+ production). Sensors detect levels (pCO2, respiratory system maintains homeostasis fo arterial levels of pO2/12.5 kPa, pCO2/5.3 kPa)

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What are the effects of alveolar pCO2 on ventilation?

Linear relationship (small changes in pCO2 produce large effects in ventilation (CO2 - major drive for ventilation). Alveolar/arterial pCO2 are the same. Top (depression of respiratory centre). Bottom (basal rhythm of resp. centre)

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What are the effects of pH change? (1)

pH change. Extreme physiological conditions (e.g. hard exercises, production of lactic acid by muscle). Pathological situation (e.g. HCO3- loss, renal disease, gut (diarrhoea), diabetes). Results in acidosis to metabolic changes (metabolic acidosis)

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What are the effects of pH change? (2)

Metabolic alkalosis (increase in pH e.g. H+ loss from stomach/vomiting or diuretic use). Low pH (acidity) - increase ventilation rate, high pH - decrease ventilation rate

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What are the effects of pH on the pCO2 ventilation curve?

Metabolic alkalosis (line shifts to the right). Metabolic acidosis (line shifts to the left). Increased pCO2 and H+ stimulate ventilation

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What is the effect of arterial pO2 variation on ventilation at constant pCO2 [5.3 kPa]?

Effect is little until value <8 kPa after which a steep rise occurs. Top - depression of respiratory centre

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What is the effect of the combined changes of pCO2 and pCO2 on ventilation rates?

Mild hypercapnia (6 kPa). The combination of hypoxia and hypercapnia is synergistic stimulation of ventilation (gap between 2 lines increases)

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Summarise features of chemical control

Small changes in pCO2 (marked changes in ventilation). Increase in h+ result in increase ventilation. Large change in pO2 required to effect respiration. Increased CO2/O2 act synergistically

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Which receptors detect pCO2, pO2 and pH?

Two types of chemoreceptors - central (CNS, in ventrolateral surface of medulla) and peripheral (carotid, aortic bodies). Chemoreceptors are separate from respiratory neurones

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Describe the actions of central chemoreceptors (1)

Detect changes in pCO2 of blood but measurement is indirect. Sense pH surrounding CSF (not blood pH, H+/HCO3- cannot use BBB). CO2/O2 freely permeable. CO2 combines with water to form H2CO3 -> H+ and HCO3- in cell and CSF

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Describe the actions of central chemoreceptors (2)

H+ in CSF is directly proportional to blood pCO2 levels. Central chemoreceptors are not responsive to pO2. Central chemoreceptors monitor CO2 in CSF

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What are the properties of central chemoreceptors? (1)

CSF - little protein (little buffering of pH, small change in pCO2 causes large change in pH). 80% response to increased pCO2 remains after removal of peripheral chemoreceptors (important). Slow response (due to diffusion of CO2 to CSF ~ 20s)

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What are the properties of central chemoreceptors? (2)

Responsible for adaptive changes to pCO2 particularly in chronic respiratory conditions

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What is the neural input for peripheral chemoreceptors in the aortic bodies?

Vagus nerve (X)

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What is the neural input for peripheral chemoreceptors in the carotid bodies?

Glossopharyngeal nerve (IX)

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Describe the structure of the carotid body

2 types of cells - glomus and sheath. Glomus cells respond to decreased pO2, increased pCO2 and H+. Release dopamine at nerve junction. Main O2 sensing cells in respiration. Show synergistic response (dopamine) to combined stimuli

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Describe the function of the carotid and aortic bodies (1)

Increased pCO2/H+, increases discharge - stimulation respiration (account of 20% of response to pCO2). pO2 decreased leads to increased discharge to stimulate respiration

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Describe the function of the carotid and aortic bodies (2)

Very fast response to acute changes in blood levels. Can detect oscillations in pCO2 and pO2 levels (e.g. during inspiration/expiration). Show synergistic responses in pO2/pCO2 levels

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Describe the function of the carotid and aortic bodies (3)

Responds to pO2 not O2 content (carotid body releases neurotransmitter when oxygen pO2 decreases)

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Outline the chemoreceptor response to changes in plasma CO2

Stimulation of central/peripheral chemoreceptors. Increase ventilation, increase plasma pO2. Results in decrease of pCO2 (negative feedback also involved)

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Which factors reduce response to CO2?

Age, sleep, genetic factors, trained athletes, morphine, increased work of breathing

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State features of pH buffering

CO2 + H2O (respiratory compensation) <-> H2CO3 <-> HCO3- + H+ (renal compensation)

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Control of Breathing

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