Respi physiology
Respiratory physiology is the study of how oxygen is brought into lungs and tissues and how carbon dixide is removed
The mainfunction of the respiratory system is gas exchanfe. Other functions inlcude host defenses, metabolism, thermoregulation and acid base balance.
The respiratpry system is functionally divided into gas exchange organ (lung) and respiratory pump.
Respiratpry pump consists of muscles, nerves, thoracic cage and brain centres.
Ventilation
is the process by which air is brought into the lungs to adequately replenish the gases that has been exchanged.
Mechanism of respiration
Are about how total pressure gradients are created so that air will flow into and out of the lungs
Breathing mechanism
Lungs are expanded and contracted into two ways
1. By download and upward movement of the diaphgram
2. by elevation and depression of the ribs
During laboured breathing, accessor muscles are used.
Pressure changes during respiration
●Pressure changes in pleural space are generated by actions of the respiratory pump
●These pressure changes are transmitted to the alveoli and responsible for the movement of air between atmosphere and alveoli
Deep breathing/forced inspiration and expiration
> strong respiratory effor
> more negative intrapleural pressures
> Lung expands more
> Acessory muscles of respiratory are involved (sternoclastomoid
Forced expiration - active process
Contraction of the expiratory muscles
Contraction of expiratory muscles
Internal intercostal muscles
Mucles of anterioir abdominal wall
Intrapleural pressure becomes positive Air ways and air flowConduction air ways
> no alveoli - no gas exchange
> anatomical dead space Respiratory zone (respiratory bronchioles, alveolar ducts, alveoli) makes up most of the lung (2.5 to 3L at rest)Airway resistance
Airway resistance is the pressure difference required for a unit of air flow
Determined by:
1. the calibre of bronchi
2. Pressure gradient in the airways
3. Density of the inhaled gas Calibre of airways and resistance
●Diameter is indirectly proportional to airway resistance
●Narrower the airway higher the resistance
Asthma ;
●Increased smooth muscle tone
●Oedema of the submucosal layer
●Obstruction of the lumen by secretions
Ways of overcoming airway resistance
Dilate airways
>Bronchiodialatoes using beta 2 agonist
Corticosteroids to reduce inflammation
Reduce the density of inhaled gas
Breathing og helium- oxygen mixture during diving
Increase pressure gradient between the atmosphere and the laveolus
>Use of acessory muscles of respiration
> Mechanical ventilation
Compliance
Strecthability/distensibility of the lung
Change in the lung volume per unit change airways/ transpulmonary pressure
More the lung expands for a given rise in the pressure, the greater the compliance
Higher the compliance, easier it is to expand
The problem in emphysema is that although increased complinace when expiration, recoil is less...so that again impedes ventilation
Relevance?
●Increased compliance ex: in old age, emphysema
- Reduced elastic tissue content
- Greater volume change per unit pressure
- Expiration is difficult due to poor restoration
●Reduced compliance(stiff lung) ex: pulmonary fibrosis, pulmonary oedema
- Less volume change per unit pressure
- Inspiration more difficult
Alveolar surface tension
> another factor which influences compliance
●Arises because attractive forces between the adjacent liquid molecules are greater than those between liquid and gas
●Result - liquid surface area becomes as small as possible
Alveolar surface tension
●Surface tension in fluid lining alveoli
●Very unstable situation
●If unopposed results in alveolar collapse
Surfactant
> surface tension lowering agent present in fluid lning laveoli
> produces by type 2 alveoli epithelial cells
> Mixture of DPPC (dipalmitoylphosphatidylcholine), other liquids and proteins
> Surfactant is formed relatively late during foetal lifeAdvantages of surfactant
Increase compliance of lung
Alveoli are made more stable by reducing the tendency of small alveoli collapse
Helps to keep alveoli dry - surface tension forces suck fluid in the alveoli
- By reducing the surface forces, surfactant prevents transudation of fluid
Lung volumes and capacities
Helps in assessment of lung function
Measured by spriometer except
- Functional residual capacity - Total lung capacity - Residual volume (measured by helium dilution technique/plethysmography)
Tidal volume
- volume of air inspired or expired with each normal breathe (500ml)
Inspiratory reserve volume
- maximum extra volume of air that can be inpired over ad above the TV when the person inspires with full force
Expiratory reserve volume
- maximum extra volume of air that can be expelled at the end of a normal tidal expiration\
Inspiratory capacity
- TV + IRV - amount of air that can be inspired beginning at the normal expiratory level, filling the lungs to the maximum
Functional residual capacity
- ERV + RV = amount of air that remain in lungs after a normal expiration
Vital capacity
- IRV + TV + ERV = maximum amount of air that can be expelled after first filling the lungs with a maximal inspiration
Total lung capacity
- maximum volume to which the lungs can be expanded with the greatest possible effort
* the best parameter is the vital capacity when assessing respiratory capicity and failure in conditions like myasthenia gravis and snake bite
Timed vital capacity - FEV1
> Fraction of the vital capacity expired during the first second of a forced expiration
> A normal healthy adult will exhale about 75% or more of the VC in the first second
These parameters with related to obstructive to restrictive lung diseases
Obstructive lung disease (asthma, COPD)
> FEV1 reduced due to the narrowing of bronchi
> VC is unchanged
> Ratio is reduced (<75%)
Restrictive lung diseases (lung fibrosis)
- fribrous tissue is stiff. Lung loses its ability to stretch. Therefore TLC and VC are low.
- but there is no significant onstruction in the airways
- ratio is normal or high
Uneven ventilation
Regional differences
In upright position
- Lower regions ventilated better than upper zones
- ventilation per unit volume is better in lower zones
In supine position
- Apical ventilation = basal ventilation
- lower most (posterioir) > upper most (anterior) Blood flow is also greatest at the base of the apex The relative change in blood flow from the apex to the base is greater than the relative change in ventilation So, ventilation/perfusion ratio is low at the base and high at the apex The high p02 at the apex probably accounts for the preference of adult tiberculosis for the region because it provides more favorable environment for this organism Calculation of ventilationTidal volume = 500mlRespiratory rate = 15/min (12-20)Total ventilation = TV * RR500ml * 15min = 7500ml/minRespiratory minute volume = Total ventilation
●Amount of alveoli that reach the alveoli = TV - DSV (dead space volume)
●Alveolar ventilation (VA) = (TV - DSV) * RR
●Factors influencing VA
- Tidal volume
- Respiratory rate
- Dead space
Two physiological shunts
1. Bronchiol veins => Pulmonary artery
2. Coronary veins => left side of heart
Why are composition of alveolar and atmospheric air different?
1.Alveolar air is only partially replaced by atmospheric air with each breath
2.Oxygen is constantly diffused into pulmonary blood from alveoli
3.CO2 is constantly added to alveolar air from pulmonary blood
4.Atmospheric air is humidified in the air passages and water vapour dilutes all the other gases
Gas exchange
Occurs at blood gas interface (alveolar capillary membrane)
Respiratory membrane is very thin and has a very large surface area because enormous number of small sacs ad capilaries are wrapped around the alveoli
Factors affecting the rate of has exchange across the respiratory membrane
Proportional to
> Surface area
> partial pressure difference
> solubility
Inversely proprotional to
> thickness
> sqaure root of thr molecular weight
Diffusion capacity
- measures the ability of the lung to transfer gas
(functional intergrity of the alveolar capillary membrane)
●Diffusion is most efficient when
- Surface area of the transfer is high
- Blood is readily able to accept the gas
- Capillary blood flow
- Hb available
Shunts in the lungs
●Venous blood entering the arterial side of the circulation without undergoing gas exchange
- Physiological
- Bronchial veins draining into pulmonary veins
- Coronary veins draining into left atrium
- Pathological
- Unventilated but perfused alveoli
Pulmonary vascular resistance - PVR
●Very low
●1/10 of systemic vascular resistance
●Due to the absence of muscular arterioles
●PVR becomes even smaller when the pressure within it rises by
- Recruitment - previously closed capillaries open
- Distension - vessels increase in calibre
●Vascular resistance of extra-alveolar vessels is low at larger lung volumes because they are pulled open as the lung expands
Regulation of pulmonary blood flow
●Active
- Autonomic supply
- Local factors (histamine, serotonin, NO)
- Systemic factors (pO2, pCO2 changes in blood)
●Passive
- Cardiac output
- Gravity
●Under normal conditions, PVR and distribution of flow is mainly controlled by passive factors
Active control in alveolar hypoxia
> Occurs when Pa02 is reduced
> Contraction of smooth muscle in the walls of small arterioles in hypoxic regions
> Doesnt depend on central nervous connection
> HYPOXIC PULMONARY VASOCONSTRICTION(this is to prevent a shunt from happening otherwise!!)Effects of Hypoxic pulmonary vasoconstriction
●Direct blood away from hypoxic regions of the lung
Relevance
1.At high altitude
2.At birth
●In utero, the foetal PVR is high
●At delivery when neonate takes the first breath pAO2 is increased
●PVR is decreased
●Pulmonary blood flow is increasedGas transport - Oxygen transport
●O2 delivery system - CVS + RS
- Amount of O2 entering the lung
- Adequate gas exchange
- Blood flow to the tissue (cardiac output, vascular bed)
- Capacity of blood to carry O2
●Transported in two ways
- Bound to Hb
- Dissolved
Amount of O2 in blood depends on
●Hb (97%)
- Amount of Hb
- Affinity of Hb to O2
●Dissolved O2 (3%)
●Deoxyhaemoglobin - tense configuration (T)
●When first O2 molecule is bound, bonds holding globin chains are released (R) - relaxed configuration (TR interconversion)
●More binding sites are exposed. Affinity is increased greatly
●High pO2 - O2 binds with Hb (pulmonary capillaries)
●Low pO2 - O2 releases from Hb (tissues)
Hb and O2
●What is saturation?
% of binding sites which have O2 attached
100% saturation - all binding sites are full
Features
●Sigmoid shape because TR interconversion
●Steep lower part
- small change in pO2, saturation is high
- It normally occurs at tissue level
- Peripheral tissues can withdraw large amounts of O2 for only a small drop in capillary pO2
●Flat upper part
- Little reduction in oxygenation at alveoli won't disturb Hb saturation
●P50
- Partial pressure of O2 when Hb saturation is 50%
Dissolved O2
●Has a linear relationship with PaO2
●Higher the partial pressure, higher the dissolved O2
●Deoxygenation of Hb at tissue level facilitate the transport of CO2 by Hb
●Oxygenation of Hb at alveolar level will facilitate the elimination of CO2
Acclimatization
Variety of compensatory mechanisms occuring on rising to a high altitude
Principal means by which acclimatization occurs are
1.A great increase in pulmonary ventilation
2.Increased no. of RBCs
3.Increased diffusing capacity of the lungs
4.Increased vascularity of the peripheral tissues
5.Increased ability of the tissue cells to use oxygen despite low pO2Hypoxia
O2 deficiency at tissue level
1.Hypoxic hypoxia (hypoxaemia) - PaO2 low
1.Anemic hypoxia - PaO2 normal but amount of Hb available to carry O2 is reduced
Both can co-exist
3. Stagnant / Ischemic hypoxia - O2 delivery to tissues is inadequate inspite of normal PaO2 and Hb
Ex: cardiac failure
4. Histotoxic hypoxia - amount of O2 delivered to a tissue is normal but utilisation is abnormal
Ex: cyanide poisoning
Disorders causing Hypoxic hypoxia
●Lung failure ( Gas exchange failure)
●Shunt
●Pump failure ( ventilatory failure)
Respiratory conditions causing Hypoxic hypoxia
Pump failure
●Muscle fatigue
●Mechanical defects in the chest wall
●Neuropathies which affect motor nerves to respiratory muscles
●Myopathy
●Depression of respiratory controller in brain
Lung failure
●Ventilation Perfusion Imbalance (V/Q mismatch)
- Lung collapse : shunted alveoli with perfusion but no ventilation
- Pulmonary embolism : ventilated but not perfused
●Defects in diffusion - pulmonary fibrosis
Ventilation Perfusion Imbalance
●CO2 content of the arterial blood is generally normal in such situations because extra loss of CO2 in overventilated regions can balance the reduced loss in underventilated areas
Effects of hypoxia
●Compensatory
●Non compensatory
Compensatory mechanisms to increase O2 delivery
●Increased alveolar ventilation
●Increased diffusion capacity
●Increased no. of RBCs - polycythemia
●Cellular changes - increased 2,3 DPGCyanosis
Non compensatory effect of hypoxaemia
●Dusky, dark bluish discolouration of tissues due to concentration of reduced (deoxygenated) haemoglobinin capillary blood being more than 5g/dl
●Peripheral - impaired local circulation (extremities or fingers)
●Central - impaired general circulation (tongue and lips)
Effects of hypoxia on brain
Sudden severe drop in PIO2 can cause death
Less severe changes
●Impaired judgment
●Drowsiness
●Dulled pain sensibility
●Excitability
●Disorientation
●Headache
●Vomiting
●Tachycardia
●Hypertension
Central(medullary) chemoreceptors
●Increased PaCO2
●Increased H+ in CSF and brain ECF
●Stimulate central chemoreceptors
●Stimulate respiration
●In addition, increased PaCO2 causes cerebral vasodilation which promotes diffusion of CO2 into CSF and brain CSF
Peripheral chemoreceptors
●Carotid body - glossopharyngeal nerve
●Aortic body - vagus nerve
●There is a graded increase in impulses of the afferents when arterial pO2 is low or pCO2 is high
●Significance of very high blood flow
- O2 need of cells can be met by dissolved O2
- Therefore receptors are not stimulated in anemia, CO poisoning
RELATED ANATOMY
Trachea
The trachea commences in the neck at the level of the lower border of
the cricoid cartilage (C6) and runs vertically downwards to end at the
level of the sternal angle of Louis (T4/5), just to the right of the mid-
line, by dividing to form the right and left main bronchi
The sternal angle of Louis (T4/5)
●1. It is the level of the junction between the sternum body and its manubrium. This joint is a symphysis. There are a few symphyseal joints in the body and they include an early symphysis menti between the two mandibles and a symphysis pubis between the two pubic bones.
●2. It represents the plane that separates the superior from the inferior mediastini.
●3. It is the plane at which the bifurcation of the trachea occurs at the carina trachea
●4. It is the plane of the division of the pulmonary trunk.
●5. It is the plane of the arch of aorta.
●6. It is plane that contains the ligamentum arteriosum
●7. The plane that contains superficial and deep cardiac plexuses
●8. At this plane, the ascending thoracic duct escapes from the right to the left.
●9. It is the plane of the junction of the 2nd sternocostal articulation.
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Relations
Lying partly in the neck and partly in the thorax, its relations are:
Cervical
●anteriorly — the isthmus of thyroid gland, inferior thyroid veins,
sternohyoid and sternothyroid muscles;
●laterally — the lobes of thyroid gland and the common carotid
artery;
●posteriorly — the oesophagus with the recurrent laryngeal nerve
lying in the groove between oesophagus and trachea
Thoracic
In the superior mediastinum its relations are:
●anteriorly — commencement of the brachiocephalic (innominate)
artery and left carotid artery, both arising from the arch of the aorta,
the left brachiocephalic (innominate) vein, and the thymus;
●posteriorly—oesophagus and left recurrent laryngeal nerve;
●to the left—arch of the aorta, left common carotid and left subcla-
vian arteries, left recurrent laryngeal nerve and pleura;
●to the right—vagus, azygos vein and pleura
●splaying of the carina, with the increase of the tracheal bifurcation angle to over 90 degrees
●An enlarged left atrium can have many clinical implications, such as:
Ortner syndrome: left recurrent laryngeal nerve palsy secondary to compression from enlarged left atrium
dysphagia megalatriensis: compression of esophagus between the enlarged left atrium and vertebral bodies
●There are about 25 divisions in all between the trachea and the alveoli
●The first seven divisions are bronchi that have:
- walls consisting of cartilage and smooth muscle
- an epithelial lining with cilia and goblet cells
- submucosal mucus-secreting glands
- endocrine cells – Kulchitsky or amine precursor and uptake decarboxylation (APUD) cells containing 5-hydroxytryptamine (5-HT, serotonin).
The next 16–18 divisions are bronchioles that have:
- no cartilage and a muscular layer that progressively becomes thinner
- a single layer of ciliated cells but very few goblet cells
- granulated Clara cells that produce a surfactant-like substance.
●The ciliated epithelium is a key defence mechanism.
●Each cell bears approximately 200 cilia beating at 1000 beats per minute (b.p.m.) in organized waves of contraction.
●Mucus, which contains macrophages, cell debris, inhaled particles and bacteria, is moved by the cilia towards the larynx at about 1.5 cm/min (the ‘mucociliary escalator’
●The bronchioles finally divide within the acinus into smaller respiratory bronchioles that have alveoli arising from the surface
●Each respiratory bronchiole supplies approximately 200 alveoli via alveolar ducts.
The alveoli
●There are approximately 300 million alveoli in each lung.
●Their total surface area is 40–80 m2
●The epithelial lining consists
1.Mainly of Type l pneumocytes
2.Type ll pneumocytes - source of surfactant
3.Large alveolar macrophages are present within the alveoli and assist in defending the lung
●Each lobe is further subdivided into bronchopulmonary segments by fibrous septa that extend inwards from the pleural surface.
●Each segment receives its own segmental bronchus, artery and vein
The Pleura
●The pleura is a layer of connective tissue covered by a simple squamous epithelium.
●The visceral pleura covers the surface of the lung, lines the interlobar fissures, and is continuous at the hilum with the parietal pleura, which lines the inside of the hemithorax
●At the hilum, the visceral pleura continues alongside the branching bronchial tree for some distance before reflecting back to join the parietal pleura.
●In health, the pleurae are in apposition, apart from a small quantity of lubricating fluid.(pleural fluid)
The diaphragm
●The diaphragm is covered by parietal pleura above and peritoneum below
●Motor and sensory nerve fibres go separately to each half of the diaphragm via the phrenic nerves.
●Fifty per cent of the muscle fibres are of the slow-twitch type with a low glycolytic capacity; they are relatively resistant to fatigue.
Pulmonary vasculature and lymphatics
●The lung has a dual blood supply, receiving deoxygenated blood from the right ventricle via the pulmonary artery and oxygenated blood via the bronchial circulation.
●The pulmonary artery divides to accompany the bronchi. The arterioles accompanying the respiratory bronchioles are thin-walled and contain little smooth muscle.
●The pulmonary venules drain laterally to the periphery of the lobules, and eventually join to form the four main pulmonary veins.
●The bronchial circulation arises from the descending aorta. These bronchial arteries supply tissues down to the level of the respiratory bronchiole.
●The bronchial veins drain into the pulmonary veins, forming part of the normal physiological shunt.
●Lymphatic channels lie in the interstitial space between the alveolar cells and the capillary endothelium of the pulmonary arterioles.
●Lymphatic channels are richer than in any other organ Nerve supply to the lung
●Parasympathetic and sympathetic fibres (from the vagus and sympathetic chain, respectively) accompany the pulmonary arteries and the airways.
●Airway smooth muscle is innervated by vagal afferents, postganglionic muscarinic vagal efferents and vagally derived non-adrenergic non-cholinergic (NANC) fibres
●Three muscarinic receptor subtypes have been identified:
- M1 receptors on parasympathetic ganglia,
- a smaller number of M2 receptors on muscarinic nerve terminals
M3 receptors on airway smooth muscle
●Cholinergic stimulation of muscarinic receptors - bronchoconstriction
●Adrenergic stimulation of beta 2 receptors - bronchodilatation and increase bronchial secretions
●Alpha 1 adrenergic receptors - inhibit secretions
●The parietal pleura is innervated from intercostal and phrenic nerves
●The visceral pleura has no innervation.
Questions and answers
1.Regarding bronchopulmonary segments,
A. Supplied by tertiary bronchi
B.Pulmonary veins are found in the periphery
C.Bases are found towards the hilum
D.Can clearly differentiate from outside
E.During anesthesia an inhaled particle tends to go to the upper segment of the lower lobe
1.A. T - also called segmental
B. T - veins are intersegmental, artery accompanies the bronchus
C. F - apices. Bases are directed towards periphery
D. F
E. T - apical segment of the right lower lobe
02. Regarding FEV1 / FVC ratio
A.It's measured with peak flow meter
B.Steadily decreases with age
C.Less than 70% is indicative of obstruction of the airways
D.If normal can exclude lung fibrosis
E.Is useful to assess post bronchodilator response in asthmatics
02. A. F - spirometer
B. T - FEV1, FVC, FEV1 /FVC fall
C. T
D. F - can be normal or increased in lung fibrosis
E. T - to quantify reversible airway obstruction
03. Pulmonary ventilation
A.Is 6L/min in a healthy adult
B.Is equal to alveolar ventilation
C.Stable in mild to moderate exercise
D.Increases in metabolic alkalosis
E.Can be reduced due to increased intra abdominal pressure
03.
A. T
B. F - (Tidal volume 500 - Dead space 150) * RR 12 = 4200ml/min
C. F - increased
D. F - decreases due to respiratory inhibitory compensation
E. T
04. In healthy adult,
A.Anatomical dead space is equal to physiological dead space
B.Surfactant prevents alveolar collapse during expiration
C.97% of vital capacity is exhaled during 1st second of forced expiration
D.PaCO2 is the main stimulation of respiration
E.CO2 stimulation of respiration is mainly via central chemoreceptors
04. A. T
B. T
C. F - 70-80%
D. T
E. T
05. The O2 - Hb dissociation curve,
A.Relates the percentage saturation of Hb with O2, to the alveolar arterial O2 gradient
B.Is shifted to the left in metabolic acidosis
C.Is shifted to the right in massive blood transfusions
D.Is unchanged in iron deficiency anemia
E.Is closely similar to O2 - myoglobin dissociation curve
05. A. F - to partial pressure of dissolved O2 in blood
B. F - right
C. F - left due to reduced levels of 2,3 BPG in stored blood
D. T
E. F - it is a rectangular hyperbola. Hb has a sigmoid curve
Related pharmacology
Related pathology
Pathogenesis of asthma ●Trigger - not known in many (intrinsic)
●Release of mediators
●Inflammation
- Smooth muscle contraction
- Oedema of mucosa
- Hypersecretion of mucus
- Bronchial hyperactivity \ Triggers of asthma
●Infections - ex: viral URTI
●Tobacco smoke and cooking fumes
●Occupational - wood dust, grain dust, flour
●House hold - dust, pets, mould, cockroach
●Food - allergies, preservatives and colouring
●Drugs - Aspirin and NSAIDS, beta blockers
●Exercise
●Emotions
●Change in weather
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