MICN201 Respiratory physiology lecture summary notes PDF

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Lecture notes for the respiratory physiology block module ...

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Overview of the physics of the resp system Respiration is the exchange of O2 and CO2 between the environment and the tissues Respiration can be subdivided into: ● External - exchange of O2 and CO2 between atmosphere and blood flowing through the lungs ● Internal - transport of O2 and CO2 between tissues and lungs by the circulating blood, O2 consumption and CO2 production in tissues Respiration as a series of 5 steps: 1. Ventilation - process of moving air in and out of the lungs in order to supply O2 to and remove CO2 from the alveoli [BULK FLOW] 2. Gas exchange - O2 and CO2 moves across the alveoli membrane down their partial pressure gradients [DIFFUSION] 3. Gas transport - blood leaves the lungs high in O2 and low in CO2, it is pumped around the body to the cells [BULK FLOW] 4. Gas exchange - at the interface between capillaries and the cells, there is exchange of O2 and CO2 down their partial pressure gradients [DIFFUSION] 5. Cellular respiration - cells use the O2 and produce CO2 Dalton’s law of partial pressures - Pgas = Fgas x Ptotal - Need to know the % concentration of each gas and the atmospheric pressure -> Fgas = Pgas/100 - Absolute pressure at sea level today = 760 mmHg , the partial pressures are calculated. PO2 = 159 mmHg Water vapour reduces the PO2 in the trachea by about 100 mmHg → to 149 mmHg - Water vapour pressure = 47 mmHg - Pressure of inspired O2 (PIO2) = FIO2 x (barometric pressure - 47) = 0.2093 x (760 47) = 149 mmHg Partial pressure in inspired air → alveolar air Pulmonary ventilation VE = f x VT But not all the inspired air reaches the alveoli - as fresh air is inhaled it is mixed with air in the anatomical dead space, so… Alveolar ventilation VA = f (VT - D) where f = frequency (breaths/min); VT = tidal volume; D = dead space This measures the flow of fresh gases into and out of the alveoli during a particular time - Slow deep breathing increases VA and rapid shallow breathing decreases VA

Pulmonary disease - Gas transfer capacity may be impaired by: 1. Thickening of membrane e.g. pulmonary fibrosis 2. Reduction in surface area e.g. emphysema (the only obstructive disease that reduces the surface area of the pulmonary-capillary interface)

Arterial hypoxemia

1. 2. 3. 4. 5.

Reduced PB or FIO2 Hypoventilation Impaired diffusion Shunt Ventilation-perfusion mismatching

O2 dissociation curve and O2 capacity - O2 forms an easily reversible combination with Hb to give OxyHb - The maximal amount of O2 that can be combined with Hb is called O2 capacity - 1g of Hb can combine with 1.34 ml O2 - Normal blood has about 150g of Hb/L - O2 capacity = 1.34 x 150 = 201 ml O2 per L CO2 transported in 3 forms: - 10% transported as CO2 dissolved in plasma - 20% transported as HbCO2 (carbaminohaemoglobin) - 70% transported as HCO3- dissolved in plasma

Lung function tests Assess ventilation by: - Blood gases - PaO2 (hypoxia) - PaCO2 (hypercapnia) -- this is only influenced by ventilation - Lung volumes / flows - Spirometry - Peak flow rates PEFR - Exhaled Nitric Oxide (eNO) Spirometry - Measures how much and how fast - Common simple test, Mechanical / digital - Test response to therapy Divides the air in the lungs into 4 volumes ● Tidal volume ~500ml (VT) - volume of air moves in and out during normal quiet ventilation ● Inspiratory reserve volume ~3L - an extra 3L can be inspired if the external intercostal muscles are contracted too ● Expiratory reserve volume ~1.5L - an extra 1.5L can be expelled if the internal intercostal and abdominal muscles are contracted for maximal active expiration ● Residual volume ~1L - even after maximal expiration, our lungs are still partially inhaled These volumes can be grouped into capacities: ● Vital capacity ~5L - maximal breath in to maximal breath out (ERV + VT + IRV) ● Total lung capacity ~6L - if you breathe all the way in, you hold about 6L in your lungs (VC + RV) ● Inspiratory capacity - tidal volume + IRV

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Functional residual capacity ~2.5L - volume in lungs at end of tidal expiration (RV + ERV) -- represents ‘equilibrium point’ for respiratory system - to change volume from FRC need to do work

Residual volume - can’t be measured directly by spirometry, use Helium dilution - Breathe on spirometer - add known amount of He - Measure concentration at TLC (=VC + RV) - Calculate volume He has distributed into = spirometer + VC + RV - Measure spirometer + VC, RV = difference - Body plethysmography (an instrument for measuring changes in volume within an organ or whole body - usually resulting from fluctuations in the amount of blood or air it contains) Spirometry: How fast? - Forced measurements give info about FLOW - Forced vital capacity FVC - Forced expiratory volume in one second (FEV1) - Reduced with: diseases causing resistance to airflow (airways obstruction) or small lungs (e.g. scarred or fibrotic lungs) - FEV1/FVC ratio -- value / 80% of predicted - FEV1 >/ 80% predicted - FEV1/FVC ratio >/ 0.70 Spirometry - Quality control - Technician dependent / subject dependent - Acceptable effort - sharp peak, gradual return to 0 flow, at least 4 seconds - 3 acceptable attempts within 5% of each other - Often more easily seen on flow-volume tracings Flow-volume loops - The assessment of patient effort on repetitive testing - The presence of specific patterns for upper airways obstruction - Specific patterns in other disease processes confirm but add little to spirometry numbers Peak expiratory flow rates PEFR - Can be obtained during spirometry - Portable devices can be used to make measurements at home or in workplace - Rate e.g. 500L/min, not volume - Determine ‘normal’ values from nomogram - But absolute value not that useful since there is a wide range of ‘normal’ - Changes in PEFR from a person’s normal value is useful - decrease in PEFR suggest decreased flow e.g. worsening asthma - Can use to change / assess therapy

Indications for pulmonary function testing 1. Objective assessment of pulmonary symptoms 2. Categorisation of the type and severity of physiologic abnormalities 3. Documentation of progression of disease 4. Documentation of the patient’s response to therapy 5. Preoperative assessment 6. Screening for subclinical disease Restrictive lung disease - FVC decreased - FEV1 often decreased proportionate to FVC - FEV1/FVC normal or increased - May need lung volume measurements (RV, FRC, TLC) to confirm Obstructive lung disease - FEV1/FVC this increases lung compliance Airways resistance - air flow is mainly laminar flow during quiet breathing - Determined by Poiseuille’s law - Bronchoconstriction / bronchodilation important elements in airways resistance (e.g. asthma) - Main area of airways resistance = bronchi - Most of the resistance to airflow arises in the upper airway and the first 6 generations of the lower airway - The small airways contribute very little to airways resistance (++ total XS area) Factors determining airway resistance

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Bronchoconstriction e.g. activity in vagal parasympathetic fibres (reflex from of stimulating irritant and cough receptors in the airways) + local chemical mediators (histamine, leukotrienes) Bronchodilation e.g. activation of B2-adrenoceptors via circulating adrenaline or administration of sympathomimetics (e.g. isoprenaline and salbutamol) Dynamic compression of airways

Gas exchange Dynamic compression of airways: - Some airways are very collapsible - Since they are also enclosed within the thoracic cage, increased intrathoracic pressure can sometimes lead to airways collapse which increases airways resistance and limits airflow - Limits airflow in normal subjects during a forced expiration or may be exaggerated with disease e.g. emphysema (reduced lung elastic recoil and loss of radial traction or airways) - May occur in diseased lungs at relatively low expiratory flow rates - even without forced expiration -> reduced exercise ability - Counteract with ‘purse-lipped breathing’ - maintain airway pressure which splints airway open Work of breathing 1. Overcome elastic properties / stiffness of lung/chest wall system (how hard is it to expand lungs?) a. Compliance (lung / chest wall) b. Surfactant 2. Overcome airways resistance i.e. friction (how hard is it to move the air? - in and out) a. Bronchi / radius / bronchoconstriction b. Dynamic collapse ● Restrictive lung disease - increased work due to decreased lung compliance (stiff lungs) ● Obstructive lung disease - increased work due to increase in airway resistance (narrow pipes) ● Pulmonary oedema - increased work due to decreased lung compliance (stiff lungs)

Hypoventilating patient (^ PCO2) ● Work of breathing too high - decreased compliance or increased airways resistance ● or Can’t do work of breathing - fatigue, muscle weakness; depressed central control e.g. opiates ● or Not doing enough work of breathing - behavioural (sleep), panic attack Gas exchange ● O2 consumption VO2 = 250-300 ml/min ● CO2 production VCO2 = 200-250 ml/min ● Need to exchange these amounts of gases across alveolar membrane for homeostasis and be able to increase amount exchanged in exercise ● VCO2/VO2 = respiratory exchange ratio R

○ 200/250 = 0.8 is commonly used (diet dependent) Diffusion across alveolar membrane - large surface area Driven by pressure gradients - alveolar pressures are important (PAO2 and PACO2) Also dependent on alveolar perfusion - removing O2/adding CO2 to alveolar interface - need right balance of ventilation and perfusion (V/Q) PAO2 and PACO2 ● Set the alveolar end of the partial pressure diffusion gradient ● These partial pressures are determined by: ○ Composition of inspired air ○ Alveolar ventilation ○ O2 consumption or CO2 production ○ Matching of alveolar ventilation to pulmonary capillary blood flow ● ● ●

Alveolar gas equation: 150 - 40/0.8 = 100 mmHg If measure PaO2 (ABG) -- determine the difference between PAO2 and PaO2 (A-a gradient) can find if there is a problem with gas exchange - This is normally abnormal A-a gradient Non-uniform VA may be caused by:

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Uneven resistance to airflow - airway collapse as seen in emphysema, asthma, bronchitis, compression by tumors or oedema Non-uniform compliance in different parts of the lung - fibrosis, regional variation in surfactant production, pulmonary congestion or oedema, emphysema, atelectasis (collapse of lung tissue), pneumothorax, or compression by tumors or cysts Non-uniform perfusion of the lung can be caused by: Embolisation or thrombosis, compression of pulmonary vessels by high alveolar pressures, tumours, exudates, pneumothorax, destruction or occlusion of pulmonary vessels by various disease processes, pulmonary vascular hypotension, or collapse or overexpansion of alveoli

Both ventilation and perfusion increased from the lung apex to the base - the change in perfusion is greater than the change in ventilation A distribution of V/Q ratios exist even in the normal lung Functionally: alveoli at apex are relatively underperfused (overventilated); alveoli at the base are relatively underventilated (overperfused) V/Q mismatch is responsive to supplementary oxygen Other mechanisms for arterial hypoxaemia 1. Reduced PB or FIO2 2. Hypoventilation: causes include ○ High work of breathing - compliance, airways resistance ○ Damage to the chest wall or fatigue / paralysis of respiratory muscles ○ Respiratory depressants - morphine/barbiturates ○ Sleep (relative) Always increases the PaCO2 Decreases PaO2 unless additional O2 is inspired Hypoxaemia reversible by adding O2 Arterial hypoxaemia - respiratory failure PaO2 < 60 mmHg or PaCO2 > 55 mmHg Type 1 = PaO2 low, PaCO2 normal - Gas exchange problems - V/Q, shunt e.g. pneumonia, pulmonary oedema Type 2 = PaO2 low, PaCO2 high - Ventilatory failure e.g. chronic bronchitis, emphysema May co-exist Hypercapnia - pH problems - Produce about 13000 mmol CO2/day but can remove this via the lungs, just need to keep breathing. Hypo or hyperventilation -> alter PCO2 - pH abnormalities Compensation - respiratory control of CO2 and renal control of HCO3 levels ● Renal compensation of respiratory acidosis/alkalosis ● Respiratory compensation of metabolic acidosis/alkalosis

Gas transport Oxygen is carried in the blood in two forms 1- dissolved O2 - For each mmHg PO2 only 0.03ml dissolved O2 / L of blood

- Thus arterial blood with PO2 100 mmHg contains 3 ml dissolved O2/L - i.e. very ineffective for O2 transport 2 - combined with Hb - O2 forms an easily reversible combination with Hb to give oxyHb - O2 saturation of Hb is the % of the available binding sites that have O2 attached; - Arterial blood SaO2 with a PO2 of 100 mmHg is ~98% - Venous blood SvO2 with a PO2 of 40 mmHg is ~70% Upper flat part of curve - moderate changes in PO2 around the normal value in the lung (100 mmHg) have only small effects on the % saturation and therefore the amount of O2 carried by arterial blood Steep part of curve at lower PO2 - helps with unloading of O2 to the tissues. Small changes in PO2 result in unloading of large amounts of O2 to the tissues Oxygen capacity (how much oxygen could the blood carry) - The maximal amount of oxygen that can be combined with Hb is called O2 capacity - Normal blood has about 150 g Hb/L - 1g of Hb can combine with 1.34 ml O2 - So oxygen capacity = 1.34 x 150 = 200 ml/L of blood Oxygen content (how much oxygen is the blood carrying)

Changeable conditions of O2 dissociation curve Bohr effect - the O2 dissociation curve is shifted to the right by an increase in: - H+ conc, PCO2, temperature, 2,3-diphosphoglycerate (DPG) in RBCs - 2,3 DPG is a by-product of glycolysis (RBCs contain no mitochondria); increases with intense exercise training, altitude and due to severe lung diseases or anaemia - helps deliver O2 to tissues (due to rightward shift of ODC which allows more O2 to be released from Hb at a particular PO2 increased unloading) Low saturation / content -> cyanosis - Blue-purple color, most obvious in the skin, nail beds and mucous membranes, caused by lower SaO2 and is indicative of blood with a low CaO2 - Presence detectable when there is at least 50 g/l of deoxyHb (also depends on skin pigmentation, illumination and adequate capillary perfusion) - Central cyanosis (blue mouth and tongue) - due to poor oxygenation - Peripheral cyanosis - the lungs are healthy but there is poor circulation Anaemia - saturation curve stays the same, O2 content reduced, exercise problems from av difference Carbon monoxide - interferes with O2 transport by combining with Hb to form COHb (has about 250x the affinity of O2 for Hb); small amounts of CO can tie up large proportion of Hb in the blood making it unavailable for O2 carriage - reduced O2 content. Shifts curve to left more difficult to unload O2 to tissues CO2 transport Carbamino compounds formed by the combination of CO2 with terminal amine groups in blood proteins, the most important is the globin of Hb (Hb.NH.COOH) Deoxygenation of blood increases CO2 carriage - Haldane effect

Control of breathing Need to maintain normal levels of PaO2 and PaCO2 for metabolic and biochemical stability (e.g. pH) Despite largely differing demands for O2 uptake and CO2 production, PaO2 and PaCO2 are normally kept within close limits The remarkable regulation of gas exchange is made possible because ventilation is so tightly controlled Control of breathing - three basic elements 1. Central control in the brainstem which sets pattern/rhythm of breathing and coordinates sensors and effectors to maintain respiratory homeostasis 2. Sensors - central/peripheral - gather info - chemical/physical 3. Effectors - respiratory muscles - adjust ventilation ● The respiratory centre receives a variety of neural and humoral (chemical) inputs from the peripheral and central receptors

Central controller - respiratory centre - brainstem - Normal automatic process of breathing originates in impulses that come from the brainstem - Cortex can override these centers for voluntary control - The respiratory centre receives a variety of neural and chemical inputs from peripheral and central receptors

Brainstem - periodic nature of inspiration and expiration is controlled by neurons located in pons and medulla (respiratory centres). Three main group of neurons: 1. Medullary respiratory centre (beneath 4th ventricle): a. Pre-Botzinger complex - rhythm generator “pacemaker” b. Dorsal area respiratory group (inspiration) c. Ventral area respiratory group (mainly expiration) It is uncertain how the intrinsic rhythmicity of respiration occurs 2. Apneustic centre - pons ?inspiratory cut-off 3. Pneumotaxic centre - pons ?finetuning Respiratory centres - key points - Medulla / pons - Responsible for generating rhythmicity - Input from chemoreceptors, lung and other receptors and cortex - Major output via phrenic nerves Sensors - central chemoreceptors CCR - Located near the ventral surface of the medulla - Sensitive to the PCO2 but not PO2 of blood - Respond to the change in pH of the ECF/CSF when CO2 diffuses out of the cerebral capillaries Sensors - peripheral chemoreceptors PCR - Located in the carotid and aortic bodies

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Respond to decreased arterial PO2, increased PCO2 and H+ Rapidly responding (imp in exercise) ~90+% of the O2 response and ~20-30% of the CO2 response comes from these receptors

Ventilatory response to CO2 1. PaCO2 is the most important stimulus to ventilation under most conditions and it is normally tightly controlled +/- 3 mmHg 2. Most of the stimulus comes from the central chemoreceptors but peripheral chemoreceptors also contribute and their response is much faster 3. The ventilatory response to PCO2 is reduced by sleep (tolerate slightly higher levels of CO2), increasing age and genetic factors 4. The response is magnified if PaO2 is lowered Ventilatory response to hypoxia 1. Only peripheral chemoreceptors involved 2. Negligible control during normoxic conditions 3. Augmented by hypercapnia - ventilation is stimulated at PaO2 levels above 60 mmHg 4. Hypoxia control becomes important at high altitude and in long term hypercapnia caused by chronic lung disease Chronic hypoventilation (e.g. chronic bronchitis / emphysema) can result in CO2 retention -the resulting high arterial PCO2 and acidosis leads to increased HCO3 retention in order to normalise pH (blood and brain) Thus, the stimulus at the CCR (H+) is ‘reset’ to near normal levels Hypoventilation due to increased work of breathing and V/Q mismatch, often makes patients hypoxic which can become the main stimulus to drive ventilation - If you administer a high O2 mix → remove hypoxic drive -> will hypoventilate -> CO2 will drastically increase Non-chemical control of breathing - Receptors that are located in the airways and lungs can affect respiration through afferent connections to the respiratory centers from the vagus nerves - Lung receptors - Slowly adapting stretch receptors - Rapidly adapting stretch receptors - Juxtacapillary receptors - Other receptors - Nose/upper airway, joint/muscle, arterial baroreceptors, pain and temp...