Esa 3 - Respiration Session 5

Front 1

Define the terms hypoxia, hypercapnia, hypocapnia, hyperventilation, hypoventilation.

Back 1

Hypoxia – decreased po2 below 8kpa in arterial blood
Hypercapnia – high pco2 above 6.1kpa
Hypocapnia – low PCO2 below 4.8kpa
Hyperventilation – removal of CO2 from lungs is more rapid that its production resulting in hypocapnia -> respiratory alkalosis
Hypoventilation – removal of CO2 from lungs is less rapid than its production resulting in hypercapnia -> respiratory acdiosis

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Front 2

Describe the effects on plasma ph of hyper and hypo ventilation

Back 2

Hyperventilation causes decreased plasma PCO2 thus more H ions and HCO3 react to form more CO2. This raises the PH of the blood.
Hypoventilation causes increased plasma PCO2 thus more CO2 and water react to form more H+ ions and HCO3.

Front 3

Describe the terms respiratory acidosis, respiratory alkalosis, compensated respiratory acidosis and compensated respiratory alkalosis.

Back 3

Respiratory acidosis is caused by hypoventilation where less CO2 is removed by the lungs than is produced so alveolar PCO2 rises causing dissolved CO2 to rise more than [HCO3] producing a fall in plasma ph. If the condition persists, the kidneys respond by excreting and producing more HCO3 thus restoring the co2/HCO3 ratio and Ph. This is compensated respiratory acidosis.

Respiratory alkalosis is caused by hyperventilation where more CO2 is removed by the lungs than is produced so alveolar PCO2 falls causing fall in dissolved CO2 and thus an increase in ph. More H+ ions are needed to react with hydrogen carbonate to restore the ph. These hydrogen ions are removed from albumin, which also transports Ca2+. Therefore there is an increase in transporters calcium so free calcium ion levels decrease – hypocalcaemia. Hypocalcaemia causes tetany and paresthesia.
If this condition persists, the kidneys respond by excreting more HCO3, restoring ratio and ph. This is compensated respiratory alkalosis.

Front 4

Define the terms metabolic acidosis, metabolic akalosis, compensated metabolic acidosis and compensated metabolic alkalosis.

Back 4

In metabolic acidosis, acid is produced by the cells which binds to HCO3 reducing the concentration of HCO3 and thus more CO2 reacts with water to form H+ ions. The ratio can be restored to normal by removing CO2 by hyperventilation. This is compensated metabolic acidosis. However the [HCO3] will not be normal until corrected by the kidneys.

In metabolic alkalosis HCO3 is produced and retains in the plasma, such as in vomiting where there is no stimulating for the HCO3 to enter the duodenum as there is no acid in the duodenum. This will also cause hypokalaemia due to the hydrogen/potassium antiporter. If there is decreased hydrogen ion concentration then hydrogen ions are pumped out by the cells into the blood and potassium is taken in. The blood ph may be corrected by elevating PCO2 by hypoventilation but this is not sufficient so the kidney must excrete more HCO3.

Front 5

Describe the acute effects of changes in PO2 and PCO2. Which is more important to control?

Back 5

A small fall in PO2 does not cause great effects as it will remain saturated until it drops to 8kpa. At this partial pressure the patient is hypoxic and hyperventilation will occur ( due to peripheral chemoreceptors). A small increase in PCO2 is very dangerous as PCO2 is directly linked to acid base reactions and so a small increase in PCO2 will lower the Ph.
PCO2 is therefore more important to control tightly, where as PO2 is only a problem if it falls drastically.

Front 6

DESCRIBE THE LOCATION AND FUNCTION OF THE PERIPHERAL CHEMORECEPTORS AND THEIR ROLE IN THE VENTILATORY AND OTHER RESPONSES TO HYPOXIA.

Back 6

The peripheral chemoreceptors are located in the carotid bodies at the bifurcation of the carotid artery into external and internal and the aortic bodies at the aortic arch.
The carotid and aortic bodies are stimulated by a fall in oxygen supply relative to their own oxygen usage which is small. A high rate of blood flow through the structures ensures that they do not normally change their response until the PO2 is low. On stimulation of the carotid bodies, information is carried to the respiratory centre in the medulla oblongata via the glossopharyngeal nerve and on stimulation of the aortic bodies; it is via the vagus nerve.

They stimulate
- Increase in tidal volume and rate of respiration -HYPERVENTILATION
- Changes in circulation directing more blood to the brain and kidneys
- Increased force of contraction of the heart
They do NOT adapt and so there is a respiratory drive as long as PO2 is low.

The peripheral chemoreceptors sensitive to CO2 and PH are also found in the carotid bodies and the aortic bodies. They respond quickly to very large changes in PCO2, greater than 1.3kpa, but they are not crucial for the precise regulation of respiration.
They respond well to changes in PH and are effective in compensating acidosis and alkalosis.

Front 7

Describe the location and function of the central chemoreceptors, their role in the ventilator respiratory changes in arterial PCO2 and the roles of the cerebro spinal fluid, blood brain barrier and choroid plexus in that response.

Back 7

The central chemoreceptors are located on the ventral surface of the medulla and are exposed to cerebro-spinal fluid. These receptors respond to a fall in CSF ph. The CSF is separated from the blood by the blood brain barrier, which allow CO2 (as well as O2, glucose and water)to cross but don’t allow the passage of HCO3 ( as well as fatty acids and H+ ions).
Therefore the PH of the CSF is determined by its own hydrogen carbonate/carbonic acid buffer system. Instead of haemoglobin which is absent in CSF, choroid plexus cells pump HCO3 into and out of CSF. The dissolved CO2 in CSF is determined by plasma PCO2. A rise in PCO2 of plasma will cause a drop in ph of CSF. This is detected by the central chemoreceptors which cause hyperventilation within 30seconds of rise of PCO2 in plasma. When the PCO2 is restored, the central chemoreceptors decrease rate of ventilation. If this negative feedback does not occur and the ph is not returned to normal due to additional sitmulus to ventilation (hypoxia) or because of lung disease, then the choroid cells will alter the concentration of HCO3 to restore the ratio. Because of its small volume PH CSF is corrected much more quickly than blood ph. As ph CSF is corrected, the control system is reset to operate around a different CO2. Therefore it will take a larger increase in PCO2 to stimulate central chemoreceptors. Thus hypercapnia and hypoxia persist.

Front 8

Define respiratory failure

Back 8

Respiratory failure is when the arterial PO2 falls below 8KPA when breathing are at sea level.
In type 1 respiratory failure the arterial hypoxia is accompanied by normal or low PCO2.
In type 2 respiratory failure, the arterial hypoxia is accompanied by an elevated PCO2 above 6.7kpa.

Front 9

What 5 factors are necessary to maintain arterial PO2 in the normal range (10-13.3kpa)?

Back 9

1. Normal PO2 in inspired air
2. Normal alveolar ventilation
3. Normal alveolar capillary membrane
4. Matching of ventilation and perfusion of alveoli throughout the lung
5. All of the right ventricular output should pass through gas exchanging alveoli

Front 10

List the potential causes of hypoxaemia.

Back 10

1. Low PO2 in inspired air
2. Hypoventilation
3. Diffusion impairment
4. Ventilation and perfusion mismatch in the lung
5. Abnormal right to left cardiac shunts – cyanotic heart disease eg tetrology of falot, transposition of the great vessels (conotruncal septum fails to develop spiral form), univentricular heart.

Front 11

Describe hypoxia caused by low inspired PO2. Describe acclimitisation.

Back 11

Describe hypoxia caused by low inspired PO2.
The oxygen transport system is functioning normally but the air breathing in does not have a high enough PO2 due to being at high altitudes. Acute exposure is dangerous as acclimatization takes time.
Acclimatisation involves the hypoxia being associated with a low PCO2 as hyperventilation is triggered by peripheral chemoreceptors detecting low PO2. Also there is adaptation of central chemorecetors, re-seting the control system to work around a lower PCO2. The alkalinity of the blood due to low PCO2 is corrected by kidneys excreting more HCO3. The HB levels also increase due to increased erythropoietin secretion by the kidneys. Also there is an increase in red cell 2,3 bisphosphoglycerate ( intermediate in glycolysis) which shifts the dissociation curve to the right so more oxygen is given to the tissues. Within the tissues there is an increase in number of mitochondria and within muscle an increase in myoglobulin.

Front 12

Describe hypoxia caused by hypoventilation.

Back 12

Insufficient atmospheric air is moved in and out of the lung to maintain normal alveolar PO2 and PCO2 values. Alveolar PO2 decreases and alveolar PCO2 increases -> arterial P02 decreases and arterial PCO2 increases -> type 2 respiratory failure. The treatment is ventilator support. Hypoventilation can be caused by
1. Neuro-muscular problems: respiratory centre depression causing slow or irregular respiratory rate. This may be due to head injury or drug overdose. Disease or damage to any part of nerve pathways from respiratory centre in the medulla oblongata to respiratory muscles will cause respiratory muscle weakness.
2. Chest wall (mechanical) problems – scoliosis (side-ways spine curvature), kyphosis ( over curvature of thoracic vertebrae), morbid obesity, trauma, pneumothorax ( collapsed lung due to broken pleural seal).
3. Difficulty in ventilating lungs due to airway obstruction, COPD and asthma ( airway narrowing is severe and widespread) and severe fibrosis

Front 13

Describe hypoxia due to poor ventilation perfusion matching.

Back 13

If too much blood flows through a pulmonary capillary for the ventilation of its alveolus there is a ventilation-perfusion mismatch and the arterial PO2 will fall. This cannot be compensated by extra oxygen uptake by blood at better ventilated alveoli as that blood is already fully saturated with O2. However the low pCO2 removal in some alveoli can be compensated by increased CO2 removal in other alveoli as PCO2 removal is not limited and CO2 easily diffuses across the alveolar capillary membrane.
Therefore this is a type 1 respiratory failure as arterial hypoxia is accompanied by a normal or low PCO2.
Poor ventilation of some alveoli is caused by pneumonia, early stages of acute severe asthma and respiratory distress syndrome of newborn where small alveoli collapse into large alveoli due to absence of surfactant to minimise surface tension.
Poor perfusion of some alveoli is caused by a pulmonary embolism.

Front 14

Describe hypoxia due to diffusion impairment.

Back 14

The barrier to diffusion between alveolar air and pulmonary capillary blood is normally very small. Co2 diffuses 20 times more readily than oxygen and therefore if there is a diffusion impairment, the arterial PCO2 will be normal or low – type 1 respiratory failure.
The barrier can become increased by:
- Structural changes – lung fibrosis,
- Increased length of diffusion pathway –pulmonary oedema increases path length by introducing an extra layer of fluid to cross ( usually 5 layers).
Diffusion is also impaired if total area available for diffusion is reduced as in emphysema ( damaged alveolar walls).

Front 15

Descrbe emphysema

Back 15

Emphysema is a chronic obstructive pulmonary disease with airflow obstruction indicated by reduced FEV1/FVC ratio of less that 70% which is irreversible with a bronchodilator or steroids. In emphysema, elastases are produced which destroy the alveolar septa and capillaries and permanent enlargement of air spaces (bullae) which can result from smoking or alpha 1 antitrypsin deficiency. Centrilobular emphysema involves the upper lung zones and is associated with cigarette smoking, that causes inflammation in alveoli and thus the increased elastase production. Panacinar emphysema involves lower lung zones and is associated with alpha 1 antitrypsin deficiency ( antitrypsin inibits proteases).
The bullae cause decreased lung elastic recoil and as bronchioles are kept open by the alveoli, the bronchioles collapse on expiration causing airway obstruction and leading to hyperinflation. The increased compliance makes the intra pleural pressure less negative and so air is harder to draw in. This results in difficulty in breathing, tachypnoea, barrel chest ( increased anterioposterior chest due to hyperinflation), malnutrition, use of accessory muscles and purse lipped breathing, which increases pressure in upper airways and thus limits distal airway collapse. There is increased TLC, RV and lung compliance and reduced diffusion capacity.
On flow diagrams, the FEV1 will be reduced, showing an obstructive expiratory disorder and the FEV1/FVC ratio will be less than 70%. On peak flow, there will be scalloping and a decrease in peak flow.
X-rays may indicate bullae, hyperinflation and flattened diaphragms

Front 16

Describe chronic bronchitis.

Back 16

Chronic bronchitis is associated with airway obstruction caused by chronic mucosal inflammation, mucous gland hypertrophy and mucus hypersecretion along with bronchospasm. It is characterised by daily morning productive cough ( mucus) on most days for 3 months in 2 successive years in the absence of airway tumour, infection or uncontrolled cardiac disease. Most patients have normal total lung capacity, functional residual capacity, residual volume, diffusing capacity and lung compliance. Patients with severe chronic bronchitis have reduced respiratory drive (hypoventilation) caused by hypercapnea which is associated with bounding pulse, vasodilation, confusion, headache, flapping tremor and papilloedema. Hypoxemia is due to ventilation perfusion mismatch and causes polycythaemia (increased red cells) and pulmonary hypertension due to hypoxic pulmonary vasoconstriction. Pulmonary hypertension can cause cor pulmonale ( right heart failure – pitting oedema at ankles and sacrum).

Front 17

Describe the gold scale for determining the severity of COPD.

Back 17

GOLD 1: FEV1 >70% of normal value = mild form
GOLD 2: FEV1 50-70% of normal value = moderate form
GOLD 3: FEV1 30-49% of normal value = severe form
GOLD 4: FEV1 <29% of normal value = very severe form

Front 18

Describe management of COPD.
First of all if the patient smokes they must be helped to quit.

Back 18

Short-acting bronchodilators are used first to open the airways and relieve symptoms as and when they occur but if a person with stable COPD remains breathless or has exacerbations, either long-acting beta-agonist inhalers or long-acting anticholinergics inhalers should be used as a maintenance therapy (ie long term treatment taken regularly). Inhaled anticholinergics are very important in COPD because they target the major reversible component of airflow obstruction in COPD – cholinergic tone (ie constriction of the muscles in the tiny airways controlled by the nerve transmitter acetylcholine).
Anticholinergics drugs are not used n asthma.
If the person’s lung function is still poor then an inhaled corticosteroid is added in combination with the bronchodilator to reduce inflammation. Long term corticosteroid use should be avoided as it can cause many problems, There are several different combination inhalers currently in use.
Patients producing large amounts of sputum may benefit from mucolytic drugs which break down the thick sputum that clogs up the airways.
Those patients who have become greatly limited by severe COPD should be assessed for long-term oxygen therapy (LTOT) where oxygen is supplied through a mask or nostril tubes, and can significantly improve their quality of life.
Pulmonary rehabilitation programme strengthen respiratory muscles and improves quality of life and excerise tolerance while reducing hospitalisations but has no effect on lung function.
Prevention of acute COPD exacerbations includes strep pneumococcus and haemophilis influenza vaccinations.
Also a bullectomy may be performed to surgically remove bullae in lungs – thin walled, air filled spaces in lungs that limit ability to breath.

Front 19

What are the side effects of long term corticosteroid use?

Back 19

Corticosteroids can cause immunosuppresion – poor wound healing, oral candidiasis, thin skin ( purple striae), central adiposity and moon face due to increased lipogenesis, diabetes due to suppressed insulin, glaucoma, hypertension, muscle weakness ( proteolysis), cataracts and osteoporosis.

Front 20

Define COPD

Back 20

COPD is an umbrella term for chronic bronchitis, emphysema or both. It is characterised by irreversible small airway obstruction, hyperinflation, mucus hypersecretion and increased work of breathing. Patients have symptoms of dyspnoea at rest or on exertion. The obstruction is shown by decreased FEV1 and FEV1/FVC ratio ( usually 70%) which does not change markedly over several months. Unlike asthma the airflow obstruction is fixed and so NOT fully reversible (less than 15% improvement with bronchodilator or steroid therapy). Risk factors such as smoking, over 50, male, childhood chest infections, atopy, low socioeconomic status, alpha1 antitrypsin deficiency, heavy metal exposure and pollution trigger an abnormal inflammatory response causing chronic respiratory symptoms with acute exacerbations eventually leading disability and respiratory failure. Individuals may also have genetic predisposition to COPD (alpha 1 antitrypsin deficiency). Chronic hypoxiaemia can lead to pulmonary hypertension which can cause cor pulmonale (right heart failure).
Type 2 respiratory failure can result in COPD - hypoxia and hypercapnea.
Asthma is not a COPD because it is reversible small airway obstruction

Front 21

In the normal individual breathing is 'driven' by carbon dioxide. Which partial pressure do you think is most important in a subject with long term hypercapnia and hypoxia? What might happen to such a subject if you give them oxygen to breathe?

Back 21

Oxygen. Because the central chemoreceptors can become unresponsive to pCO2 in patients with long term hypercapnia. if they are given oxyge, the hypoxia will be corrected and this removes the hypoxic stimulation of the peripheral chemoreceptors, which is the stimulus that drives ventilation in these patients with
longstanding hypercapnia.

This leads to ventilatory (respiratory) depression. This will cause the hypercapnia to
get worse.