Respiratory System Flashcards
How is a negative pleural pressure established?
The lung elastic recoil is inward while the chest wall elastic recoil is outwards.
What is elastic recoil?
Having the property of being able to spring back and return to the original shape after being distorted.
How does gas move in to the alveoulus?
Atmospheric pressure is greater than alveolus pressure.
Inspiratory neural activity from the brain draws the diaphragm down and contracts the external intercostal muscles to pull ribs up and out. This causes the negative pressure difference in the alveolar space.
Inspiratory time < expiratory time.
How to gas move out of the alveolus?
Alveolar pressure is greater than atmospheric.
No inspiratory neural activity so lung does elastic recoil inwards. This is passive.
Inspiratory time < expiratory time.
What happens during large/forced expiration?
Diaphragm is pushed upwards as abdominal muscles contract. Internal intercostals contract, pushing chest wall inwards by moving ribs downwards.
What causes SOBOE (shortness of breath on exertion) in COPD?
Decreased lung elastic recoil, Obstructive airways disease, Static and dynamic hyperinflation, Inability to efficiently increase tidal volume.
Where is voluntary control of breathing controlled?
The cortex.
Removal of cortex + upper pons leads to slow gasping breaths.
Where is autonomic breathing controlled?
The pons, medulla and spinal cord.
Removal of cortex + upper pons leads to slow gasping breaths.
Removal of pons causes return to rhythmic breathing.
Removal of medulla leads to breathing stopping.
How is rhythmic breathing generated?
Medullary neurones control rhythmic breathing: ventral respiratory group (VRG) and dorsal respiratory group (DRG).
Inspiratory neurones activate expiratory neurones and cause expiration (contraction of diaphram and intercostals).
Expiratory neurones inhibit inspiratory neurones.
So a cycle of rhythmic breathing commences.
What is the effect of large inspiration on the rhythm of breathing?
Controlled by medullary neurones: ventral respiratory group (VRG) and dorsal respiratory group (DRG).
Inspiratory neurones cause a large activation of expiratory neurones. This causes contraction of expiratory muscles and inhibits inspiratory neurones.
Leads to a rhythm/cycle.
What are the feedback inputs to the respiratory rhythm generator?
Lung receptors (afferent fibres carried in vagus nerve):
Slow adapting receptors,
Rapidly adapting receptors,
C-fibre endings.
Chemoreceptors:
Central chemoreceptors,
Peripheral chemoreceptors.
What is the effect of lung receptor activity on the pattern of breathing?
If vagal nerves are cut, volume increases and rate decreases (slow, deep breaths).
If vagal nerves are stimulated, volume decreases and rate increases (fast, shallow breaths).
Slowly adapting receptors respond to a stimulus and then keep firing.
Rapidly adapting receptors respond to a stimulus and then slow down as they get used to it.
What are slowly adapting lung receptors (SARs)?
AKA stretch receptors.
Mechanoreceptors situated close to airway smooth muscle.
Stimulated by stretching of airway walls during inspiration.
Help initiate expiration and prevent over inflation of the lungs.
Initiate Hering-Breuer inflation reflex (prolonged inspiration produces prolonged expiration).
Afferent fibres are myelinated.
What are Rapidly adapting lung receptors (RARs)?
AKA irritant receptors.
Located in airway epithelium.
Primarily a mechanoreceptor (like SARs) so respond to rapid lung inflation.
Respond to chemicals (e.g.histamine), smoke, dust.
RARs in trachea and large bronchi initiate cough, mucus production, bronchoconstriction.
Afferent fibres are myelinated.
What are the C-fibre endings in the lungs?
Unmyelinated nerve fibres that provide sensory input from airway and lung structures.
Stimulated by increased interstitial fluid (oedema) and various inflammatory mediators (histamine, prostaglandins, bradykinins). Linked to vagus nerve.
Bronchial C-fibres Endings in the airway epithelium; and;
Pulmonary C-fibres (juxtapulmonary capillary receptors, J-receptors) Endings close to the pulmonary capillaries.
What is the chemoreceptors response to arterial O2 and CO2?
Arterial pH is driven by CO2.
For central, has to travel across blood-brain barrier. Central chemoreceptors on surface of medulla detect [H+] once pCO2 has dissociated and sends info to medullary rhythm generator.
Peripheral chemoreceptors have a FAST response to:
Arterial pO2, arterial pCO2, and arterial [H+].
Central chemoreceptors have a SLOW response to:
Arterial pCO2, only.
Sensory nerve is the vagus, motor nerve is the phrenic.
What is the ventilatory response to CO2?
As pCO2 increases in normoxia (normal O2), minute ventilation also increases.
In hypoxia (low O2), minute ventilation will be greater than in normoxia.
In hyperoxia (high O2), minute ventilation will be less than in normoxia.
What is the ventilatory response to hypoxia (low O2)?
Hypercapnia (raised pCO2).
How is breathing altered due to sleep?
Midbrain neural activity stimulates breathing during wakefulness (“wakefulness drive to breathe”). Neural activity (cortex, pons, medulla) also regulates muscles in the UPPER AIRWAY (i.e. above the trachea).
During sleep:
Respiratory drive decreases (loss of wakefulness drive) causing reduction in metabolic rate and reduced input from higher centres such as pons and cortex;
Loss of tonic neural drive to upper airway muscles.
Consequences of loss of wakefulness drive is that patients with impaired ventilation (e.g. muscle weakness, severe lung disease, neuropathy or spinal deformity) first develop respiratory failure (raised arterial CO2) during sleep.
What is muscle airway muscle activity?
What happens to it during sleep?
Phasic: contraction of upper airway muscles, opening of upper airway, facilitates inward airflow, (similar to activity in diaphragm/external intercostals which generate inspiration).
Tonic: continuous background activity, tends to maintain patent airway, varies with state of alertness, (similar to activity in skeletal muscles which maintain posture).
During sleep: loss of tonic activity to upper airways, airways collapse (obstruct) to give cessation of breathing (= apnoea).
How does partial pressure of oxygen affect gas exchange?
At equilibrium, partial pressure of gas in solution equals partial pressure of gas above liquid. But most oxygen is carried by haemoglobin rather than dissolved.
Gas exchange is driven by partial pressure. Partial pressure of oxygen in the alveolus equals the partial pressure in the blood draining the alveolus.
However, due to shunting and dead space, there is no apparent equilibrium if we consider the lung as a complete unit - partial pressure of O in arterial blood is lower than the alveolus.
Why is the pO2 of arterial blood lower than we might expect?
Anatomical shunts:
A small amount of arterial blood doesn’t come from the lung (Thebesian veins);
A small amount of blood goes through without seeing gas (bronchial circulation).
Physiological shunts (decrease V {ventilation}) and alveolar dead space ( decreased Q {perfusion}):
Not all lung units have the same ratio of ventilation (V) to blood flow (Q);
V/Q mismatch.
What is physiological dead space?
Anatomical dead space represents the conducting airways where no gas exchange takes place.
Alveolar dead space represents areas of insufficient blood supply for gas exchange and is practically non-existent in healthy young but appears with age and disease.
Physiological dead space = anatomical dead space + alveolar dead space.
What does the ventilation to perfusion ratio mean?
V/Q
If ventilation = perfusion then will get perfect gas exchange (shunting aside…).
In the lung, naturally have V/Q mismatch with less blood and air going to the top of the lung
What is ‘normal’ V/Q mismatch?
Zone 1 - top of the lung:
Less airflow and blood flow but V>Q, so increased V/Q, and pO2 is higher.
Zone 2 - middle of lung:
V/Q is normal.
Zone 3 - bottom of lung:
More ventilation and more blood flow but V<Q , so decreased V/Q, and pO2 is lower.
In healthy lungs the physiological V/Q mismatch generally cancels itself out. But in disease, it may become more apparent, and lung diseases can cause additional V/Q mismatch leading to gas exchange problems.
Why do patients become hypoxaemic?
Hypoventilation:
Cause of low oxygen levels as not enough oxygen is being provided for gas exchange.
Ventilation perfusion (V/Q) mismatch (pathological vs. physiological):
In healthy lungs the physiological V/Q mismatch generally cancels itself out. But in disease, it may become more apparent, and lung diseases can cause additional V/Q mismatch leading to gas exchange problems.
Or both of the above.
What causes hypoventilation?
Respiratory: restrictive vhest physiology, pulmonary hypertension, hypoxemia/hypercapnia;
Central Nervous System: decreased central respiratory drive;
Airway: potential difficult airway, sleep apnea;
Cardiovascular: coronary artery disease, congestive heart failure;
Others: difficult vascular access, difficult positioning.
What causes failure of the ventilatory pump?
Won’t breathe: control failure:
Brain failure to command e.g. drug overdose;
Can’t breathe - broken peripheral mechanism:
Nerves not working e.g. spinal injury,
Muscles not working e.g. muscular dystrophy,
Chest can’t move e.g. severe scoliosis,
Gas can’t get in and out e.g. asthma/COPD.
What happens to CO2 levels in hypoventilation?
Oxygen levels go down in hypoventilation.
During normal ventilation CO2 diffuses out of blood into alveolus following a partial pressure gradient.
CO2 is mostly dissolved in blood rather than bound to haemoglobin.
If there is lower ventilation, then CO2 accumulates in the alveolar space meaning less can be removed from the blood. So hypoventilation leads to increased pCO2.
What causes V/Q mismatch?
Conditions that thicken the alveolar wall or narrow and block small airways,
Lung infection such as pneumonia (fluid in alveoli),
Bronchial narrowing such as asthma and COPD (although they can also progress to hypoventilation and type 2 resp failure),
Interstitial lung disease,
Acute lung injury
What causes V/Q mismatch in pneumonia?
Pneumonia causes inflammation and damage in the small airways and alveoli. Airways narrow and fluid builds up in alveoli.
Results in hypoxaemia because blood does not come into contact with adequate O2. CO2 will also increase but this does not impact overall CO2 levels in blood.
What happens to arterial O2 In V/Q mismatch?
Blood leaving areas of low V/Q ratio has low PaO2 and high PaCO2.
High PaCO2 stimulates ventilation.
‘Extra’ ventilation goes to areas of normal lung and areas with high V/Q ratio. But extra ventilation can’t push O2 content much higher than normal.
Blood from both areas mixes but cannot overcome the low oxygen level.
Hyperventilation: high PaO2 but content not high.
Low V/Q ratio: low PaO2 and content.
What happens to arterial CO2 in V/Q mismatch?
Blood leaving areas of low V/Q ratio has low PaO2 and high PaCO2.
High PaCO2 stimulates ventilation. ‘Extra’ ventilation goes to areas of normal lung and areas with high V/Q ratio so get blood with low CO2.
Blood from both areas mixes so overall CO2 is normal.
Low V/Q ratio: high PaCO2 and content.
Hyperventilation: low PaCO2 and content.
What is type 1 respiratory failure?
PaO2 is low but PaCO2 is NOT high.
V/Q mismatch is the main problem.
Common causes: pneumonia, (pulmonary embolism), acute severe asthma, COPD.
What is type 2 respiratory failure?
PaO2 is low and PaCO2 is high.
Ventilatory failure (hypoventilation) is main feature.
Common causes: opiate toxicity, severe COPD (acute/chronic), acute severe asthma, Pulmonary Oedema in acute Left Ventricular failure.
How do we treat Type 1 respiratory failure?
Give oxygen - this is a short-term life saving measure.
The fundamental problem is inadequate gas exchange. Improve gas exchange by treating underlying cause.
In some cases mechanical ventilation is required.
How do we treat Type 2 respiratory failure?
Give oxygen - controlled in COPD patients with chronic respiratory failure.
Treat the underlying cause to reverse hypoventilation e.g. bronchodilators for acute asthma or opiate antagonists for overdoses.
Support ventilation: non-invasive ventilation/invasive ventilation.
What are the physiological roles of hydrogen ions?
Needed in mitochondria, protein conformation/function, and metabolism.
How is hydrogen ion concentration regulated?
Human hydrogen ion concentration tightly regulated.
Homeostasis achieved through production ~ excretion and buffering.
How are hydrogen ions produced?
Carbon dioxide: 20000 mmol/d, produced by tissue respiration, lung excretion.
Lactic acid: 1300 mmol/d, produced by glycolysis, oxidation or gluconeogenesis.
Ketoacids: 400 mmol/d, produced by ketogenesis, oxidation.
Urea synthesis: 1140 mmol/d, produced by ureagenesis, oxidation of amino-acids.
How is Hydrogen ion homeostasis maintained by buffers?
Buffering – a buffer solution resists changes in pH when acid or base is added to it.
Most important mechanism for regulating pH is through the buffers dissolved in blood – mainly bicarbonate (HCO3-).
H+ + HCO3- <–> H2CO3 <–> CO2 + H2O
[H+ ] = K.[H2CO3 ]/[HCO3-]
[H+ ] = K’.[CO2 ]/[HCO3-]
[H+ ] = K’’.pCO2 /[HCO3-]
so… [H+ ] = pCO2 /[HCO3-]
Another important buffer is haemoglobin (the chloride shift). The Hb group can either hold an O2 or a H+, so when high pCO2, Hb drops O2 (helps it get released into tissues) and picks up H+, affecting the equilibrium of the equation above. The HCO3- that corresponded to the H+ is switched for a Cl- in the plasma to balance changes.
There are other buffers like phosphate and proteins.
There is also the exchange of intracellular K+ for H+ –> intracellular shift of H ions and extracellular shift of K.
How is acid-base homeostasis maintained in the lungs?
H+ is excreted rapidly by increasing the amount of CO2 that we exhale. This shifts the below equation to the right as CO2 is removed:
H+ + HCO3- <–> H2CO3 <–> CO2 + H2O
How is acid-base homeostasis maintained in the kidneys?
H+ is excreted slowly in the kidneys (takes 2-3 days). The bicarbonate is regenerated, decreasing [H+]. Below equation is thus shifted.
H+ + HCO3- <–> H2CO3 <–> CO2 + H2O
What is acidosis?
Excess H+ ions >45 nmol/L.
Respiratory & metabolic causes. Homeostatic mechanisms will try and ‘compensate’.
What is alkalosis?
Reduced H+ ions <38 nmol/L.
Respiratory & metabolic causes. Homeostatic mechanisms will try and ‘compensate’.
What is respiratory acidosis?
High pCO2 causes increased [H+].
[HCO3-] can increase which lowers [H+], leading to compensated respiratory acidosis (bicarbonate generation and renal hydrogen excretion).
Caused by CO2 retension from a malfunction in the excretory mechanism or it’s control.
Examples:
CNS depression/disease or neurological disease (narcotics, stroke, spinal cord lesions, motor neurone disease)
Defects in respiratory function (mechanical - myasthenia, thoracic trauma, pneumothorax; pulmonary disease - restrictive/extensive fibrosis, obstructive - chronic bronchitis/severe asthma, impaired perfusion - massive pulmonary embolism).
What is respiratory alkalosis?
Low pCO2 causes decreased [H+].
[HCO3-] generation can decrease and renal excretion of H= decreases, which would compensate to raise [H+], leading to compensated respiratory alkalosis.
Caused by increased rate of excretion of CO2, stimulation of respiratory centre.
Examples:
Hyperventilation;
Stimuli to respiratory centre (cortical - pain, fever; local - trauma, tumours; drugs/toxins - salicylate, liver failure; hypoxaemia - R to L shunts, pulmonary disease).
What is metabolic acidosis?
[H+] increases and pCO2 decreases which initially lowers [H+] but then [H+] increases again.
Compensatory responses include buffering leads to further fall in [HCO3-], increased renal H+ excretion (if renal dysfunction not the cause) and hyperventilation (H+ stimulates chemoreceptors, Kussmaul - deep, sighing, lowers pCO2 which lowers H+, limit to how far pCO2 can fall as we need to breathe).
Often due to kidney disease/failure, acid builds up in the body:
Increased H+ generation,
Decreased H+ excretion,
Decreased buffering capacity.
Examples:
Increased acid formation - ketoacidosis (diabetic), lactic acidosis (hypoxia), poisoning (salicylate, methanol);
Reduced excretion - renal failure, renal tubular acidoses (types 1 and 4);
Loss of bicarbonate buffer - gastrointestinal (diarrhoea, pancreatic fistula), renal (renal tubular acidosis type 2)
What is metabolic alkalosis?
[HCO3-] increases which causes low [H+] and as a result pCO2 increases.
Often due to kidney disease/failure, excess loss of H+, alkali administration.
Bicarbonate is filtered by the kidneys so for metabolic alkalosis to persist inappropriate renal reabsorption of filtered bicarbonate must occur. This can be due to extra cellular volume contraction, potassium deficiency, mineralocorticoid excess.
Example:
Saline responsive - gastrointestinal (vomiting, gastric drainage), urinary (diuretics - especially in CCF, nephrotic syndrome);
Saline unresponsive - ass’d with hypertension (primary hyperaldosteronism, Cushing’s), not ass’d with hypertension (severe K+ depletion, Bartter’s syndrome).
What is the biochemistry of types of respiratory acidosis?
Acute respiratory acidosis:
pCO2 increased, high H+;
Bicarbonate normal or rising
Chronic respiratory acidosis:
pCO2 high, high normal H+;
Compensatory rise in bicarbonate
Acute on chronic respiratory acidosis:
pCO2 high, high H+, high bicarbonate
What are the effects of respiratory acidosis?
Of underlying disorder;
Of hypoxia - SOB, drowsy, cyanosis;
Of hypercapnia - Neurological (anxiety, coma, headache, extensor plantars, myoclonus); Cardiovasular (systemic vasodilatation)
What are the effects of respiratory alkalosis?
Of underlying disorder;
Of acute hypocapnia - cerebral vasoconstriction (lightheadedness, confusion, syncope, fits), fall in ionized calcium – preioral, peripheral paraesthesia);
Of cardiovascular - increased heart rate, chest tightness, angina.
What is the biochemistry of types of respiratory alkalosis?
Acute:
Decrease pCO2, decrease H+, small decrease in bicarbarbonate
Chronic:
Renal compensation results in only marginally low H+, further fall in bicarb (no lower than 12 mmol/l)
What is the biochemistry of metabolic acidosis?
Increase H+, decrease HCO3-;
Hyperventilation causes decreased pCO2;
Increased extracellular K+;
Anion gap normal in bicarbonate loss but raised in increased acid production.
What are the effects of metabolic acidosis?
Cardiovascular: negative inotropic effect (if severe)
Oxygen delivery: right shift of oxyhaemoglobin dissociation curve - facilitates O2 delivery; reduced 2,3-DPG which causes left shift of curve but takes some hours - impairs delivery
Nervous system: impaired consciousness - little correlation with H+
Potassium homeostasis: Redistribution of H+ into cells in exchange for K+, plasma [K+] rise whilst intracellular [K+] and total body [K+] are depleted
Bone: if chronic acidosis -> buffering by bone phosphate, leads to decalcification
How is protection against pathogenic bacteria provided?
Colonisation: commensal flora and colonisation resistance, normal swallowing reflex, epiglottis.
Swallowing: neurological and anatomical factors.
Lung anatomy: mucus and Ciliated epithelium, ‘mucociliary escalator’; cough reflex.
Immunity (innate and adaptive): soluble factors (IgA, defensins, collectins, lysozyme), alveolar macrophages, B- and T-cells.
What characterises upper respiratory tract illnesses?
Viral illnesses: Rhinoviruses (45-50%), Influenza A virus (25-30%), Coronaviruses (10-15%), Adenoviruses (5-10%), Respiratory Syncytial viruses (5%), Parainfluenza viruses (5%).
Usually transient, complications: sinusitis, pharyngitis, otitismedia, bronchitis, rarely pneumonia.
May lead to bacterial super-infection.
Influenza A virus in particular causes systemic symptoms.
What are common respiratory viruses?
Rhinoviruses; common cold, bronchitis, sinusitis.
Coronaviruses; colds but occasionally severe respiratory illnesses.
Adenoviruses; upper respiratory tract infection, pharyngitis, bronchitis occasional pneumonia.
Respiratory Syncytial viruses; bronhiolitis in small children, severe illness in nursing home residents, pneumonia in immunocompromised.
Parainfluenza viruses; croup.
Influenza A virus; Flu.
SARS-CoV-2 (COVID 19).
What are some emerging respiratory virus infections?
SARS-CoV-2 (Covid-19):
Severe respiratory illness with respiratory failure. Emerged as cause of major global pandemic 2019. High mortality and major economic impactt.
SARS-CoV: Severe acute respiratory syndrome associated coronavirus. Outbreak spread from China in 2002. Severe respiratory illness with respiratory failure.
Middle East Respiratory Syndrome novel Coronavirus (MERS-nCV): Individual cases spread from Middle East in 2012. Similar to SARS but low person to person spread.
Avian Influenza: Novel forms of Influenza A virus. Occasional human cases with severe illness. South-east Asia. Associated with exposure to poultry. Low person to person spread to date.
What is Pharyngitis aetiology?
b-hemolytic streptococci (Streptococcus pyogenes, Lancefield Group A streptococci)[10-30%].
Other streptococci, Fusobacterium necrophorum [10%], Mycoplasma pneumoniae [3-14%] occurs in epidemics, Corynebacterium diphtheria (travel e.g. Russia), Neisseria gonorrhoea and other sexually transmitted infections.
Viral (70-80%); rhinovirus, adenovirus etc.
Glandular fever Epstein Barr virus.
Acute HIV infection.
(ensure full history including sexual history and travel)
What is sinusitis?
Usually viral (as per causes URI).
Bacterial sinusitis (distinguish these from theviral cases to avoid inappropriate antimicrobial use): unilateral pain purulent discharge ± fever of >10d or presenting acutely or with complications.
Micro-organisms; Streptococcus pneumoniae (40%), Haemophilus influenzae (30-35%), Other Moraxella catarrhalis, streptococci.
Complications: brain abscess, sinus vein thrombosis, orbital cellulitis.
What is acute epiglottitis?
Formerly an illness of children 2-4 years old who presented with fever, dysphagia, drooling and stridor.
Caused by Haemophilus infuenzae type B (Hib) but now rare due to use of Hib vaccine.
Adults can also have the disease: most severe due to Haemophilus influenzae, also from causes of pharyngitis (other bacterial infections of airway).
Additional pathogens inimmunocompromised e.g. AIDS.
What is bordatella pertussis?
Gram-negative, aerobic, pathogenic, encapsulated coccobacillus bacterium of the genus Bordetella, and the causative agent of pertussis or whooping cough.
Acellular vaccine may not give life long immunity and vaccination may have reduced boosting from natural infections.
Clinical features:
Incubation 7-10 (5-21d),
Catarrhal phase 1-2 weeks; rhinorrhoea, conjunctivitis, low-grade fever and at end of phase lymphocytosis,
Paroxysmal phase 1-6 weeks coughing spasms, inspiratory ‘whoop’ post-ptussive vomitting, cough>14d,
Convalescent phase.
Adults chronic cough, paroxysms of coughing and 50% post ptussive vomitting but fairly specific for pertussis.
Complications; pneumonia, encephalopathy, subconjunctival haemorrhage.
What is croup?
Acute laryngo-treacheobronchitis.
A disease of children, 6 yo, most 3mo-3years).
Mainly due to Parainfluenza viruses, (also RSV, IAV and other respiratory viruses).
What is bronchiolitis?
Infections due to Respiratory syncytialvirus (RSV) [80% - rarely other viruses].
Inflammation of bronchioles and mucus production cause airway obstruction.
