Week 1: CTB Flashcards
Define Pressure
P - Force exerted per unit area
Define Pressure Gradient
DeltaP - Difference in forces exerted (per unit area) at either end/side of an object e.g. a tube or membrane
Define Flow (Q)
The VOLUME of fluid passing a given level of the circulation/airways per unit time (ml/s or l/min)
e.g. in Cardiovascular System remains constant throughout (cardiac output ~5l/min)
Define Velocity (v)
The rate of movement of fluid particles along a vessel/airway (cm/s)
Define Resistance (R)
A force that tends to oppose the flow of a substance
Explain the relationship between flow, pressure gradient and resistance.
- Flow is generated by a pressure gradient
- Flow proportional to pressure difference between the ends of vessels & airways if all other things are equal
- For a given pressure gradient, flow is determined by the RESISTANCE of the vessel/airway
- Pressure gradient = Flow x Resistance
- DeltaP = QR
Outline the factors determining resistance in a tube (3)
- Radius - Inversely Proportional
- Length - Proportional
- Viscosity of fluid - How easily layers of laminar flow move over each other
Explain the relationship between flow (q) , velocity (v) and cross-sectional area (A) in connected tubes
- At a given flow, velocity is inversely proportional to cross-sectional area (A) = πr²
- V = Q/A
- When the pressure gradient is constant, mean velocity is proportional to r² (radius)
What is Laminar flow?
- Layers of fluid moving over eachother parallel to tube
- Fluid does not move with same velocity across width of tube
- Velocity lowest at edges
- Velocity highest at centre of tube
- Laminar flow will mean that the width of the tube greatly affects its resistance
Explain the principle of Poiseulle’s Law and its relationship to flow
- Affect on flow
- Flow = Pressure gradient / Resistance
- Flow is directly proportional to the fourth power of the radius of the tube (r^4)
Explain ‘Flow is directly proportional to r^4’
This is Poiseulle’s Law, this means that if we double the radius, flow will increase by 16 times. Small changes in radius have a huge impact on flow
Define Viscosity
How easily the layers of laminar fluid move over each other
Outline the influences of particulates on flow e.g. blood
- Blood composition affects viscosity and thus flow.
- E.g. Haematocrit, % of RBC in blood volume
- Plasma proteins
- Laminar flow - RBC tend to get borne along in most rapidly moving stream in the centre of blood vessels
- Does not have a big impact on blood flow but can be altered in certain conditions
What can affect blood viscosity?
- Major determinant - Haematocrit - % RBC in blood volume. Increase in number of RBC can increase viscosity affecting flow.
- Can be caused by physiological conditions e.g. living at high altitude to increase oxygen carrying capacity of blood
- Pathological conditions e.g. Haematological malignancies, response to hypoxia
What is turbulent flow?
The layers of laminar flow break up and flow becomes disordered
What makes turbulent flow more likely?
- If Velocity is high (e.g. secondary to a narrowed tube)
- Viscosity is low
- Tube diameter is high
- Tube branching or irregular surfaces
In what forms are Turbulent flow relevant to clinical application?
- Turbulent flow is noisy
- Bruits (in blood vessels due to stenosis)
- Murmurs (turbulent flow around a heart valve due to stenosis / not closing properly)
- Wheeze
- Stridor (obstruction in the upper airways e.g. larynx/trachea)
Compare laminar and turbulent flow through a tube
- Laminar flow is flow parallel to the tube, whereby there is are layers of flow where the middle at which velocity is highest and sides where velocity is lowest. All fluid travelling in the same direction uniformly.
- Turbulent flow is when the layers of laminar flow break up and flow becomes disorganised
Compare the effects of resistances in series and resistances in parallel
- In series - Resistance is added for vessels/airways in series
- When many tubes arranged in parallel, effective cross-sectional area is greater, overall resistance is reduced.
Where are tubes arranged in parallel?
- Lower parts of tracheobronchial tree
* Capillaries
Where are tubules arranged in series?
Resistance vessels i.e. small arteries and arterioles
Describe the pattern of flow, resistance and pressure over the branching networks of the cardiovascular and respiratory systems
- Flow is constant
- Resistance is reduced at parallel branching sites e.g. capillaries and lower parts of tracheobronchial tree
- Resistance is highest at small arteries and arterioles arranged in series. Very tightly controlled via contraction and relaxation of smooth muscles within these vessels.
What is distensibility of tubes?
- Particularly veins.
- Blood inside vessels creating pressure (intravascular p.), external pressures acting on vessel outside (extravascular p.).
- Overall - Transmural p.
- Determines whether vessel stays the same size, distends, or collapses
What is Transmural pressure?
- Transmural pressure = Intravascular pressure - Extravascular pressure
- Determines distensibility of vessels, especially veins
Describe how distensibility of tubes affects the relationship between flow and pressure and can lead to capacitance.
- Vessels distends with increasing intravascular pressure, transiently more blood will flow in than out
- Distensible vessel will store blood (Capacitance)
- Veins particularly compliant, holds 70-80% of circulating blood volume
Describe the relationship between Radius and Resistance + Flow
- Flow is proportional to r^4
* Resistance is inversely proportional to r^4
What does Boyle’s Law state?
At a given temperature, the pressure and volume of an ideal gas are inversely proportional.
P1V1 = P2V2
What layers make up the Intercostal muscles?
- External Intercostal muscle
- Internal Intercostal muscle
- Innermost Intercostal muscle
- All muscles arranged in different directions, range of motions for function
What is the Superior Thoracic Aperture?
Uppermost area of thoracic cavity, open, allows continuity with structures in the neck
Describe the Inferior thoracic aperture
The inferior-most part of the thoracic cage, closed by diaphragm but still allows some structures to pass through e.g. oesophagus, IVC, Aorta
Describe the diaphragm attachments
- Lumbar vertebrae
- Transverse processes of L1
- Ribs
- Costal Margin
- Inferior part of sternum
Describe the Pleural Layers from Innermost to Outermost
- Serous membrane covering lungs and thoracic cavity
- Visceral Pleura adheres tightly to lungs
- Pleural Cavity containing small amount of pleural fluid
- Parietal pleura lining mediastinum, diaphragm, ribcage
Describe the function of Pleural fluid in the Pleural cavity
- During ventilation, a lot of movement + stretching of pleural layers
- Potential friction if no fluid present to ensure smooth sliding of layers over one another
- Only few ml, regulated by lymphatic system
What is the mechanism by which air moves during breathing?
Bulk flow
From high pressure to low pressure
How does Boyle’s Law relate to Ventilation?
As Pressure and Volume of an ideal gas are inversely proportional at a given temperature, lungs must create a pressure difference in order to bring air in
Explain the intrapleural pressure
- Pressure within the pleural cavity (lies between visceral and parietal pleura)
- Held at sub-atmospheric/negative pressure -4mmHg normally
- Due to outward elastic recoil of chest wall/ribcage + Inward elastic recoil of the lungs.
What is meant by Transpulmonary pressure
- Difference in pressure between alveoli and pleural cavity
- Measure of elastic forces in lungs that tend to collapse the lungs at each instance of respiration = Recoil pressure
What is meant by Transthoracic pressure?
- Difference in pressure between pleural cavity and thoracic cavity
What is meant by negative and positive pressure for ventilation?
- Negative pressure sucks air in
* Positive pressure is to blow air in e.g. when trying to assist pt via mechanical ventilation, mouth to mouth, CPAP
Describe the components to the Mechanics of Breathing
- Pressure differences that generate air flow
2. The respiratory muscles that effect pressure differences
What muscles are required during quiet breathing.
Inspiration - Diaphragm
Expiration - Passive
What muscles are required during deep breathing/forced expiration?
- Inspiration: Diaphragm, External intercostal muscles, scalenes (when upright)
- Expiration: Internal and innermost intercostal muscles, Anterior abdominal wall
Explain the process of Quiet inspiration
- Diaphragm contracts, flattens and moves down, pulling parietal pleura with it
- Ribcage expands and moves outwards and upwards
- Volume of thoracic and pleural cavity increases
- Decreases intrapleural pressure
- Intrapleural pressure exceeds elastic recoil of lungs
- Increase in lung volume
- Decrease in alveolar pressure to ~-3mmHg
- Negative pressure gradient sucking air into lungs
- Alveolar pressure returns to 0mmHg, equal to atmospheric pressure
Describe the basic concept of quiet expiration (2)
- Passive
* Elastic recoil of the lungs
Explain Quiet Expiration
- Diaphragm relaxes
- Decreased Thoracic cavity volume
- Decreased Pleural Space Volume
- Increased Intrapleural pressure (-4 mmHg)
- Decreased lung volume due to elastic recoil of lungs
- Increased alveolar pressure ~1-3 mmHg. Expels air from lungs until reaches atmospheric pressure
Process of Forced Inspiration
- Same mechanisms as quiet inspiration but with further assistance of accessory muscles
- External intercostal muscles contract upwards and outwards, to increase lateral diameter of chest and anterior posterior diameter of thorax.
- Sternocledomastoid muscle contracts to elevate sternum and medial ends of clavicle
- Scalene muscle group help pull ribcage upwards by elevating first two ribs, increasing diameter of chest
- Leading to larger change in intra-thoracic volume and pressure
Process of Forced Expiration
- Active process
- Abdominal muscles contract to increase intra-abdominal pressure by decreasing intra-abdominal volume
- Pressure of abdominal organs forces diaphragm upwards and depresses lower ribs
- Also assisted by internal and innermost intercostal muscle contraction
- Some action of pelvic floor muscles
- Decreases volume of thorax, further expelling air from lungs
Define Lung Compliance
- A measure of how volume changes as a result of the pressure change / The ability of the lungs to expand
- Compliance of Lungs and Chest wall is inversely correlated with their elastic properties
- Respiratory muscles must overcome this during inspiration and expiration
Describe the factors that affect lung compliance
- Chest wall - elasticity of the thorax
- lungs - elastic tissues of the lungs + surface tension
Define elasticity in terms of lung compliance
The resistance to stretch And ability of a structure to return to its normal shape and size. Opposite of compliance
What are the basic functions of the respiratory system? (4)
- Provides Oxygen to body
- Eliminates carbon dioxide
- Moistens, warms, filters air we breathe
- Allows air to reach lungs
What are the functional divisions of the respiratory tract? What are their functions
- Conducting zone - Warm, humidify, and filter air as moves through respiratory tract
- Respiratory zone - Gas exchange
What makes up the Conducting zone of the respiratory tract?
Airways from level of the pharynx, larynx, trachea, extending down to terminal bronchioles
What makes up the Respiratory zone of the respiratory tract?
Respiratory bronchioles, alveolar ducts, alveolar sacs
Describe the main histological features of the Nasal Cavity - Nasal Mucosa.
- Surface epithelium: Ciliated pseudostratified columnar epithelium
- Basement membrane
- Lamina propria (rich vascular network)
- Submucosa: Contains Seromucous glands (secrete fluid that moistens air - streaks of pink inside ducts purple), Acinar secretory units (purple)
What cells types are found in the Nasal Mucosa?
Ciliated pseudostratified columnar epithelium, some goblet cells embedded.
What are the function of cilia in the nasal mucosa?
Cellular projections, sweep away particulates from the lungs
What are the function of seromucous glands in the nasal submucosa?
Secrete watery mucus to filter and warm air
What does the nasal submucosa consist of?
- Dense connective tissue
* Submucosa contains glands, blood and lymph vessels and lymph tissue
What is the role of goblet cells?
Produce mucus, helps to filter and humidify inhaled air
What is the Larynx?
- Short passageway between nasal cavity and trachea, supported by cartilage to maintain open airway.
- Contains skeletal muscle connected to ligaments
- Ligaments vibrate two sets of vocal folds (/cords) to produce sound (phonation)
What vocal cords/folds are found in the larynx? How are they identified in histology?
- Vocal (true) cord - Inferior - Underlying core of skeletal muscle (vocalis muscle)
- Vestibular (false) vocal cord - Superior - No muscle, lymph tissue and seromucous glands
What are the functions of the larynx folds in phonation (producing sound)
- Vocal (true) cord - Produces sound during phonation
- Vestibular (false) vocal cord - Produces resonance during phonation
What epithelium do the larynx folds consist of
- True cord - Non-keratinised stratified squamous epithelium (protect from abrasion)
- Vestibular (false) vocal cord - Ciliated pseudostratified columnar epithelium. Also contains lymph tissue and seromucous glands
What are the components of a vocal (true) fold?
- Skeletal vocalis muscle
- Lined with non-keratinised stratified squamous epithelium
What are the components of vestibular (false) folds
- Respiratory epithelium
- Glands
- Connective tissue
What type of muscle is the vocalis muscle
Skeletal muscle of the true vocal cord of larynx
What is the Trachea? What is its main characteristic?
- Passageway for air between larynx and lungs
- Characterised by C-shaped rings of hyaline cartilage that maintain open lumen for passage of air
- Located anterior to oesophagus but deep to great vessels of heart
Describe the main histological features of the trachea
- Respiratory epithelium: Ciliated pseudostratified columnar epithelium with embedded goblet cells
- Basement membrane
- Lamina Propria - Smooth muscle with blood vessels
- Submucosa - Dense and regular, helps anchor perichondrium of hyaline cartilage
- C-shaped rings of Hyaline cartilage
- Trachealis muscle - connects cartilage on posterior surface of trachea
Describe function of trachealis muscle of the trachea
- Regulate diameter of tracheal opening
* Relaxes as food passes through oesophagus during swallowing.
What is the perichondrium of the trachea?
Outer layer of cells surrounding hyaline cartilage
What is the function of hyaline cartilage in the trachea?
Supports trachea to prevent it collapsing
Forms C-shaped ring. Thicker towards anterior aspect, narrower toward posterior aspect
Outer layers = Perichondrium
Describe the bronchial tree
- Trachea splits into 2 primary (main) bronchi
- Within each lung, bronchus splits into smaller secondary (lobar) bronchi
- Tertiary (segmental) bronchi
- Bronchioles (Respiratory –> Terminal)
- Alveolar ducts are passageways connect respiratory bronchioles to alveolar sacs
- One alveolar sac opens to cluster of alveoli at end of bronchial tree
Describe the main histological features of the main bronchi
- Respiratory epithelium with goblet cells
- Lamina Propria - Blood vessels
- Smooth muscle cells
- Submucosa
- Hyaline cartilage rings/plates - Support larger bronchi from collapse, decrease towards tertiary bronchi, irregular hyaline cartilage.
Describe the main histological features of the most distal bronchioles
- Respiratory epithelium transitions to > ciliated simple columnar epithelium > simple cuboidal epithelium as gets closer to terminal bronchiole
- Smooth muscle - Can change diameter
- Elastic fibers - Allow bronchioles to stay open
- Adventitia - Connective tissue anchors functional tissue (parenchyma) of lungs within thorax
Describe the main histological features of alveoli
- Type I pneumocyte - Squamous cells that form walls of alveoli, contribute to blood-air barrier
- Type II pneumocyte - Cuboidal cells bulge into air space, rounded nuclei light staining, many vesicles, secrete surfactant.
- Interalveolar septum - Wall that separates adjacent alveoli
- Macrophages
- Endothelial cells - Inner lining of capillaries
Where are goblet cells located within the respiratory tract? Histologically
Between epithelial cells in mucosa
Where are seromucous glands located within the respiratory tract? Histologically
In the submucosa
What is the alveolus?
Functional unit of respiration
Composed of two types of cells: Type 1 and 2 pneumocytes
What feature of the bronchial wall helps to keep the bronchi open during respiration?
Hyaline cartilage ring, particularly during inspiration
As you move from primary to tertiary bronchi, which change do you notice regarding the amount of hyaline cartilage present?
Decreases - Larger airways require more rigid cartilage to stop from collapsing during breathing. Physical constraints of smaller airways mean they cannot contain as much rigid cartilage as larger airways
How does proportion of goblet cells and seromucous glands change moving from primary to tertiary bronchi?
Decreases - Mucus cleared via mucociliary clearance. Further into respiratory tract, harder to clear mucus from airways due to distance mucus must be moved to clear and smaller lumen radius.
As you move form primary to tertiary bronchi, which change would you note regarding the amount of smooth muscle present?
Increases - Amount of smooth muscle in walls of tertiary bronchi is greater than primary bronchi. Helps stabilise the cartilage and allows greater control of size of bronchial lumen.
Is there cartilage in the bronchioles?
No. Bronchioles small enough to stay open without support from cartilage
What structural components allow bronchioles to stay open as we breathe?
Smooth muscle and elastic fibres
Why does amount of smooth muscle change as you move deeper into respiratory tract?
- Decrease in cartilage, relative smooth muscle increases
* Helps stabilise cartilage and allows greater control over size of bronchial lumen
What is the role of macrophages in alveoli?
Roam alveoli and phagocytose foreign material
Which type of cells line the alveolar capillaries?
Endothelial cells
Define the term diffusion
Movement of a substance from an area of high concentration to an area of low concentration
Define the term partial pressure
The pressure exerted by one gas in a mixture of gases. Analogous to the concentration of the gas within a mixture of gases.
What is Fick’s Law of Diffusion
- For any Pressure Gradient, the rate of diffusion across a membrane is determined by
- Area available
- Thickness of the membrane
- Properties of the gas
Outline the principles underlying Fick’s law
- Rate of diffusion is
- Directly proportional to: Partial pressure difference, solubility of the gas, surface area of alveoli.
- Inversely proportional to: Resistance of the alveolar membrane, Molecular weight of the gas
Gases diffuse through liquids at a rate proportional to their solubility. Which gas has a higher tissue solubility and high rate of diffusion?
Carbon dioxide has a much higher tissue solubility and on this basis diffuses ~20 times faster than O2
Gases diffuse through liquids at a rate proportional to their solubility. Which gas has a higher tissue solubility and high rate of diffusion?
Carbon dioxide has a much higher tissue solubility and on this basis diffuses ~20 times faster than O2
Gases diffuse through liquids at a rate proportional to their solubility. Which gas has a higher tissue solubility and high rate of diffusion?
Carbon dioxide has a much higher tissue solubility and on this basis diffuses ~20 times faster than O2
Outline the factors determine the ability of a gas to dissolve in a liquid
- Solubility - max amount of solute that can dissolve in a volume of solvent.
- Solubility varies with changes in temperature, pressure and pH, depends on chemical properties of gas and liquid
What does the alveolar-capillary membrane consist of?
- Varies from 0.2-2.5 micrometres, consists of:
- Alveolar epithelial cells
- Fused basement membrane of alveolar epithelial cells and capillary endothelium
- Pulmonary capillary endothelial cells
List factors determining the rate of diffusion of gases across the alveolar-capillary membrane (3)
- Surface area
- Thickness
- Properties of alveolar membrane
Describe the roles of the respiratory system
- Primary: Gas exchange
- Reservoir for blood & oxygen
- Metabolism of some circulating compounds
- Filter Blood
- Immune defence - Secreting immunoglobulins
Define Perfusion
The flow of blood through a tissue
Define Ventilation
The movement of air in and out of the lungs
Describe ventilation and perfusion in relation to the lungs
- Composition of alveolar air depends on relative rates of ventilation and perfusion
- Establish concentration gradient for diffusion to occur
Describe the Conducting Airways of the Lower Respiratory Tract
Consists of Trachea, Bronchi, Bronchioles, Terminal Bronchioles. NO gas exchange occurs here, only bulk flow
Describe the Respiratory airways of the Lower Respiratory Tract
Consists of Respiratory Bronchioles, Alveolar ducts, Alveolar sacs. Where gas exchange via diffusion occurs
Describe what is meant by the ‘Bellows’ system
- Responsible for ventilation: Chest wall, pleura, respiratory muscles, conducting airways, nerves, higher control centres
Describe what is meant by the ‘Gas-exchange system’
Responsible for OXYGENATION: Alveoli, capillaries, pulmonary circulation
Distinguish between pulmonary and alveolar ventilation
- Pulmonary ventilation - Movement of gas in and out of lungs, involves generation of pressure gradient in lungs to allow air to flow through airways, and respiratory muscles that effect pressure differences
- Alveolar ventilation - Movement of gas in and out of alveoli. Allows gas exchange to occur with mixed venous blood in pulmonary capillaries, oxygen (on inspiration) from alveolar air into blood and CO2 opposite (on expiration)
- Alveolar ventilation - The volume of air that actually reaches airways and can be used for gas exchange per minute
What is tidal volume (Vt)
The volume of air moved in and out of the lungs during normal, quiet breathing. Normally ~500ml
What is a measure of pulmonary ventilation?
Total/Minute Ventilation (MV) = Vt x RR
Tidal volume x Respiratory Rate
The amount of air moved into and out of the lungs per minute
What is Total/Minute Ventilation (MV). What does it measure?
- Amount of air moved into and out of lungs per minute
- Measure of Pulmonary Ventilation
- MV = Vt (tidal volume) x RR (respiratory rate)
What is Alveolar Ventilation?
- The volume of air that actually reaches the airways and therefore can be used for gas exchange per minute
- To calculate need to allow for ‘wasted ventilation’ of dead space
Define the term dead space
- Dead space represents the volume of ventilated air that does not participate in gas exchange.
- Two types of dead space: Anatomical dead space + Physiological dead space
Explain the presence and effects of Anatomical (Serial) Dead Space
- Anatomical Dead Space represents the volume of air that fills the conducting zone. About 150ml/500ml tidal volume. Does not take part in gas exchange
Explain the presence and effects of Physiological Dead Space
- Total volume of air that does not participate in gas exchange (VD)
- Physiological dead space = Anatomical dead space + Alveolar dead space
- In healthy person, physiological dead space nearly equal to anatomical dead space
What is Alveolar Dead Space?
- Alveolar (functional) dead space - Volume of ventilated alveoli that do not participate in gas exchange: There is a ventilation-perfusion mismatch.
What is meant by Ventilation-Perfusion mismatch?
Alveoli being ventilated but not perfused by capillary blood
Calculation for alveolar ventilation
Alveolar Ventilation (V^.A) = ( Tidal volume (Vt) - Dead space volume (VD) ) x RR
Why does rapid shallow breathing result in a reduced alveoli ventilation compared to slow, deep breathing?
For a given minute ventilation, rapid shallow breathing amplifies effect of dead space; whereas slow, deep breathing means more air reaches alveoli and is more efficient way of ventilating alveoli
How does Alveolar ventilation relate to carbon dioxide?
- Alveolar ventilation is affected by the rate of CO2 production (Proportional), and the Partial pressure of CO2 in the alveoli (PA CO2) (same as arterial (Pa CO2) inversely proportional
- Increasing alveolar ventilation decreases partial pressure of CO2
What is the first part of the lower respiratory tract where gas exchange can occur?
Respiratory bronchioles
A healthy person undertaking exercise has a respiratory rate of 50 bpm and tidal volume of 1L. What is their minute ventilation in L/min
MV = Vt x RR = 50 x 1 = 50 L/min
What is the difference between physiological and anatomical dead space?
Physiological dead space is the total volume of air which does not take part in gas exchange, includes the alveolar dead space and the anatomical dead space. Anatomical dead space consists of only the volume of ventilated air in the conducting airway.
What does P (little A) CO2 mean
Partial pressure of CO2 in the Alveoli
What does P (little a) CO2 mean
Partial pressure of CO2 in the arterial supply to lungs
Patient with anxiety has a respiratory rate of 25bpm, tidal volume 600ml. a) Assuming physiological dead space volume of 150ml, what is their alveolar ventilation rate? b) Assuming constant rate of CO2 production, would you expect their PA CO2 to be increased/decreased compared to normal.
a) (0.6-0.15) x 25 = 11.25 L/min
b) Decreased PA CO2. As their alveolar ventilation has increased, more CO2 is removed from alveoli and partial pressure decreases.
Explain the process of perfusion of the lungs
- Deoxygenated blood from right ventricle of heart enters pulmonary artery and branches into capillaries surrounding alveoli
- Oxygenated blood returns to left atrium of heart via pulmonary vein to be pumped into systemic circulation
- Flow is constant throughout
- Pulmonary circulation is low pressure and low resistance
Explain the function of perfusion of the lungs
- Pulmonary blood flow regulated by altering radius + resistance of pulmonary arterioles
- Some autonomic control - Vasoconstriction, Vasodilation
- Local mediators (Thromboxane A2, prostacyclin)
- Hypoxic Pulmonary Vasoconstriction - Relates to partial pressure of oxygen in alveolar gas
Explain Pulmonary flow, pressure and resistance factors.
- Can be controlled via
- dilated resistance vessels
- distensibility of the vessels (increased blood flow, expands vessel, increases radius, decreases resistance)
- recruitment of new capillaries which were closed at rest
- lung volume.
What is Hypoxic Pulmonary Vasoconstriction?
- When O2 diffuses from alveoli into arteriolar smooth muscle cells, causes them to relax
- Reduced PA O2 below a certain point, vascular smooth muscle cells respond to hypoxia by contracting
- Vasoconstriction + reduction of blood flow to area
- Diverts blood from poorly ventilated area to well ventilated area of lung.
- Prevents wasting blood flow
What can occur as a result of chronic hypoxia?
Persistently raised pulmonary vascular resistance and pulmonary arterial pressure –> Pulmonary hypertension –> Right ventricular failure aka cor pulmonate
What will happen to PA O2 if a) Ventilation alone increases b) Perfusion alone increases
a) Partial pressure of O2 in the alveolus will increase as more oxygen being supplied to alveoli
b) Partial pressure of O2 in the alveolus will decrease as more blood passing alveolus and removing O2
What will happen to PA CO2 if a) Ventilation alone increases b) Perfusion alone increases
a) PA CO2 decreases as more removed by ventilation
b) PA CO2 increases more diffuses from blood into alveolus
Describe the physiological relationship between ventilation and perfusion in the lung
Relative rates determine partial pressures of gases in the alveolus, thus driving diffusion. Ventilation/perfusion ration (V/Q). Normally 0.8 = Alveolar ventilation is 80% the value of pulmonary blood flow
What condition could result in blockage of blood flow (no perfusion) and increased V/Q?
- V/Q is infinite i.e. dead space, ventilation without perfusion
- Pulmonary embolism
What is a shunt?
Where an area of the lung is perfused but not ventilated
Describe the effect of gravity on ventilation and perfusion
- Ventilation and perfusion are not uniform throughout the lung in upright position
- Pulmonary blood flow/perfusion tends to be highest at lung bases due to increased hydrostatic pressure here keeping capillaries constantly open
- Ventilation tends to be greatest at lung base as basal lung relatively compressed, more potential for expansion than apex
- Gravitational effects on perfusion are greater than on ventilation as blood has greater density. Thus changes are not equal.
What is the outcome of the effect of gravity on ventilation and perfusion?
- Base of lung is relatively over-perfused relative to ventilation
- Apices of lung relatively over ventilated relative to perfusion
- As move down the lung V/Q ratio decreases
- Still - Variation is Insignificant in healthy individuals
- 30 yo woman presents acutely unwell. CXR shows extensive consolidation, air bronchograms and loss of right hemidiaphragm keeping with right lower lobe pneuomonia.
- What will the V/Q ratio be?
- What effect will this have on oxygen content of blood leaving affected part of lung
- What effect will this have on the overall oxygen content of the blood?
- What effect will hypoxic pulmonary vasoconstriction have in this case?
- Low V/Q ratio as accumulation of fluid and pus in alveoli reduces ventilation
- Will have a lower partial pressure of oxygen
- Reduces overall oxygen content of blood
- Reduction in perfusion to the abnormal area, means V/Q mismatch will be reduced, so proportion of shunted blood and magnitude of shunt will be reduced. Arterial oxygen sat. will increase to a certain extent.
Describe how ventilation perfusion inequality can lead to shunting
If there is a portion of affected lung e.g. pneumonia. Low V/Q leads to low oxygen saturation of blood. Mixes with unaffected areas of blood where saturation is high and output is blood from lungs with abnormally low level saturation. Effectively shunt: Blood is passing through a poorly ventilated area/unventilated area.
What features of pulmonary circulation ensure low resistance is maintained despite increases in pulmonary blood flow during exercise?
- Distensibility of pulmonary blood vessels
* Recruitment of previously closed capillaries
How does the V/Q ratio change throughout the lung for a person in an upright position? Explain?
Gravity responsible for increasing ventilation and perfusion moving down lung. Effect on perfusion greater than on ventilation. As a result V/Q ratio decreases moving down the lung.
In an upright person with healthy lungs, which part of the lungs has the lowest PA CO2 and highest PAO2. Explain
Apex of lungs, where V/Q ratio is highest. CO2 removed to greater extent by ventilation and oxygen continues to be replenished by ventilation
What term used to describe V/Q mismatch: Reduced ventilation and low V/Q ratio
Shunt
What term used to describe V/Q mismatch: Reduced perfusion and high V/Q ratio
Dead space
Outline the purpose of oxygen transport in the blood
To deliver to tissues for respiration reaction, oxygen is the ultimate electron acceptor of Electron transport chain. Reduced to water.
Describe Haemoglobin
- Tetramer (2 alpha, 2 beta global polypeptide chains) with 4 haem groups attached. Carries 4 oxygen molecules. Structure influenced by various factors and its modifications alters the oxygen affinity to the molecule.
- Haemoglobin A is main adult form
- Haem group Irons are ferrous form - Fe2+. Are porphyrin
What is meant by Relaxed and Tense Haemoglobin?
Different conformations of haemoglobin, influenced by the environment, binding of oxygen and binding of other molecules. Relaxed haemoglobin state has much higher oxygen affinity compared to tense haemoglobin which binds ~500 less strongly.
Describe the Conformation of Haemoglobin when surrounding pO2 is low
- No oxygen is bound, haemoglobin in tensed/closed state
- Hard to bind first oxygen molecule
- Initial binding requires minimum threshold pO2 (partial pressure O2)
What is Cooperativity in Haemoglobin?
- Binding initial oxygen to haemoglobin changes conformation of tetramer, opens
- Makes binding the next oxygen easier = Cooperative binding between oxygen binding sites
- Binding progressively easier as more oxygen molecules are bound
Describe the oxygen-haemoglobin dissociation curve in healthy adults
- Reversibility of O2 binding represented by dissociation curve
- Plot of amount (total oxygen = bound + dissolved) / percentage saturation of O2 bound to haemoglobin against pO2
- Curve due to cooperative binding
- Hb becomes saturated above given pO2
- Amount of oxygen bound then depends on how much Hb is available. Could be saturated but not much oxygen.
- Saturation independent of haemoglobin concentration
Describe the mechanisms by which oxygen is transported in the blood stream
- Mostly bound to haemoglobin - highly reversible reaction to Fe2+
- Very small amount dissolved in blood
Explain the Oxygen-Haemoglobin Dissociation Curve in healthy adults in regards to sites of loading and unloading
- Shows how much oxygen will be bound/released when blood is moved between areas with different partial pressure pO2 e.g. lungs to tissues.
- Draw dissociation curve - Lungs - at high pO2, higher percentage saturation
- Tissues - lower pO2 - lower percentage saturation, unloading as tissues using O2 in respiration and metabolism.
Explain the Oxygen-Haemoglobin Dissociation Curve in healthy adults
- Initially curve of O2 binding as pO2 increases is shallow
- Binding changes conformation, increases O2 affinity and facilitates further binding
- Curve steepens rapidly as pO2 rises until saturation where levels out
- Changes in affinity with binding create sigmoid dissociation curve.
Describe the key anchor points of the oxygen dissociation curve
- Unsaturated below 1kPa
- 50% saturated ~3.5kPa
~8kPa / ~90% saturation
What does it mean for oxygen diffusion into cells to become compromised?
- Limit to how low tissue (extracellular) oxygen concentration can drop before diffusion into cells is compromised.
- Once Hb diffuses into extracellular space must diffuse into the cells. Sometime cells further from capillary.
- Low pO2 in tissues generally, if extracellular conc so low there is no gradient for O2 into the cells. O2 Conc must be higher in the extracellular space.
What maintains effective gradient between capillary and cells? How?
- Tissue pO2 must be high enough to drive oxygen into cells by diffusion
- Tissues with high capillary density can tolerate greater falls in tissue pO2 e.g. heart muscle
- High capillary density, diffusion occurs across shorter distance and higher surface area allowing maintenance of effective gradient between capillary and cells.
Describe the features that alter the oxygen dissociation curve
- Environment e.g. pH, temperature, CO2, 2,3-DPG
- Molecule more tense in acid (low pH) - Near metabolising tissues e.g. lactic acid/CO2
- Increasing temperature also results in more tense conformation
- Shift the oxygen dissociation curve to the right (along x-axis)
- At any given pO2 there is less oxygen saturation than normal - Encourages offloading.
How do 2,3, diphosphogylcerate (2,3-DPG) levels affect Hypoxia?
- 2,3-DPG = Product of respiration?
- Increase in red blood cells in response to Hypoxia
- Stabilises tense state of haemoglobin
- Longer term effect
What is the Bohr Effect
In acid conditions the oxygen dissociation curve shifts along the pO2 axis to the right. Due to H+ and CO2 binding which stabilise Hb tense state. More unloading in tissues where pH more acidic/higher CO2
Outline the long-term physiological adaptations to chronic hypoxia
- Depending on cause, triggers various adaptive responses to increase O2 delivery to tissues:
- Increased erythropoietin (EPO) production
- Increased tissue capillary density
- Increased 2,3-DPG levels
- Increased ventilation
What is hypoxia?
Reduced availability of oxygen to the body tissues
Explain how carbon dioxide is transported in blood (3)
- Dissolved CO2 in blood ~10%
- As Bicarbonate (HCO3-) ~69%
- As Carbamino compounds ~21%
Large total amounts in blood
How is carbonic acid, thus bicarbonate ion formed?
- Dissolved CO2 reacts with H2O to form carbonic acid (H2CO3) weak acid - negligible amounts, dissociates to form H+ and HCO3-
- Reversible reaction, so does not rapidly produce bicarbonate as there is already a high concentration of it in the plasma
Define an acid
Any Chemical that can donate H+ (proton)
e.g. HCL –> H+ + Cl-
Define a base
Any chemical that can accept H+
e.g. Sodium Hydoxide –> Na+ + OH- Hydroxide group can add H+ to make water
Describe the Types of Acid
- Strong acids e.g. HCL. COMPLETELY dissociate in solution
- Weak acids e.g. carbonic acid H2CO3 only PARTIALLY dissociate in solution. Weak acid is in equilibrium with its conjugate base H2CO3 H+ + HCO3-, forms a buffer pair that can responds to changes in [H+] by reversibly binding H+
How to Measure Acidity
- Concentration of H+ ions in solution [H+].
- negative logarithm to base10 [H+] = pH
- pH 1-14 in moles per litre (mol/L)
What are normal blood [H+] levels / pH level?
- [H+] - 36-44 nanomoles/litre
- pH range 7.36-7.44 in human body
- Survival for short periods possible at pH values 6.8 - 8.0.
Describe the relationship between pH and [H+]
Inverse relationship between pH and [H+]. 1 unit change in pH equivalent to 10-fold change in [H+]
What is pK
- Constant for Henderson-Hasselbalch Equation
- Indicates ratio of the concentrations of dissociated and undissociated weak acid
- Gives indication of the extent of buffering at given pH
What is the Henderson-Hasselbalch Equation
- Equation which allows calculation of pH based on measurements of [HCO3-] and [CO2].
- pH = pK + log10 ([HCO3-]/[CO2])
- Can control [CO2] via lungs, and [HCO3-] via kidneys excretion.
Define a Buffer
Solution that can resist pH change upon the addition of an acidic or basic component. Consists of mixture of acid and its conjugate base.
Explain the relationship between carbon dioxide and bicarbonate in physiological systems
- Work as part of a physiological buffer system where different mechanisms control concentrations of both.
- Respiratory and renal mechanisms of control
- Respiratory - Body produces acid, H+ reacts with bicarbonate ions to form CO2, breathed out, restoring pH
- Renal - If pCO2 too high, kidney excrete less HCO3-, raises blood conc, restoring pH
Discuss the role of carbonic (anhydrase) dehydratase in human tissues
- Catalyses reaction between CO2 and H20
- Present in erythrocytes (RBC) not in plasma. Also found widely in salivary gland, stomach, pancreas, renal tubular epithelium, choroid plexus, ciliary body
- Reaction more rapid in erythrocytes
- Reaction further promoted as products of reaction removed - H+ buffered by haemoglobin, HCO3- transferred to plasma
Explain buffering of H+ by Haemoglobin
- Carbonic Dehydratase catalyses CO2 + H20 H+ + HCO3-
- Haemoglobin buffers H+ by binding histidine residues (weak bases) of globin chains
- Buffering enhanced by deoxygenation, venous blood can carry more CO2 than arterial blood
- Deoxygenation results in uptake of CO2; Oxygenation results in giving up CO2
Explain the relationship between carbon dioxide and oxygen in tissues (Bohr effect)
- Taking up of CO2 reduces the O2 affinity of haemoglobin, causes Hb to give up O2
- Bohr Effect: In acidic conditions, dissociation curve shifts to right, For any given pO2 haemoglobin binds less O2
Explain the relationship between carbon dioxide and oxygen in lungs (Haldane effect)
- Giving up of O2 increases the CO2 carriage by blood (increasing CO2 uptake)
- Haldane effect - Increasing oxygen binding reduces the affinity for H+ ions (ability to buffer CO2) by modifying the Hb conformation
What is an antigen
Molecule capable of inducing an immune response
Describe the key general features of innate immunity and adaptive immunity
- Innate Immunity - Primary line of defence, Immediate response, non-specific, recognises certain threats, no antigen presentation or clonal selection, no immunological memory
- Adaptive immunity - Secondary line of defence, delayed response, recognises all threats, antigen presentation, clonal selection, immunological memory
List components of the innate immune system
- Physical - Barriers e.g. epithelia and secretions
- Cellular - Leukocytes, Phagocytic cells, Granulocytes, Natural Killer (NK cells)
- Humoral elements - Plasma proteins - Humoral response
Describe the meaning of integration of Innate and Adaptive Immune Responses
- Adaptive immune response is very powerful and specific but many pathogens would kill in the days needed for a good adaptive response in absence of non-specific innate immune responses
Describe the physical component of the innate immune system:
- Stop infectious agents entering body:
- Physical barriers: Skin, Mucus, Respiratory cilia
- Biochemical barriers: Sebaceous secretions in skin, Lysozyme in tears, Gastric acidity, Commensal organisms
What is the route of most infectious agent entry?
Via mucosal surfaces of nasopharynx, respiratory tract, gastrointestinal tract, genito-urinary tract
Describe the function of mucus in innate immunity
- Interior epithelial surfaces covered with mucus
- Contain secreted mucins, help prevent pathogens adhering and facilitates clearance by cilia
- Peptides in mucus - Defensins kill or inhibit growth of pathogens
Describe the lineage of the leukocytes
- Multipotent Hemopoietic stem cell
- Multipotent hemoopoietic progenitor
- Common MYELOID progenitor
= Monocytes (macrophages), Neutrophils, Eosinophils, Basophils, Dendritic cells
List the different types of leukocytes
- Monocytes –> Macrophages
- Dendritic cell
- Neutrophils
- Eosinophils
- Basophils
- Mast cells
Describe the process of phagocytosis
- Adherence of microbe to phagocyte (dendritic cell, macrophage, neutrophil)
- Ingestion
- Phagosome formation
- Fusion with lysosome to form phagolysosome
- Digestion
- Formation of residual body containing indigestible material
- Discharge of waste material
- Can have antigen presentation - Dendritic cells
Describe the morphology and function of Monocytes/Macrophages
- Monocytes Circulate in blood. Macrophages differentiated monocytes, bigger, found in tissues.
- Macrophages ingest small pathogens and other materials via phagocytosis
- Have pseudopodia projections, moves by chemotaxis
Describe the morphology and function of Dendritic cells
- Present in skin, most tissues
- Long cytoplasmic extensions (dendrites) maximise SA to maximise antigen presentation to T-cells in lymph nodes and stimulation of adaptive immune response
- Phagocytosis
Describe the morphology and function of the Granulocytes
- Neutrophils, multi lobed nucleus, phagocytes with lytic enzymes within granules, including peroxidase and lysozyme - v. effective in killing ingested bacteria
- Eosinophils bi-lobuled nucleus, most important in defence against larger parasites. Purple-staining large granules in cytoplasm.
- Basophils non-phagocytic and release active substances from granules. Blue-staining granules.
Describe the morphology and function of Natural Killer (NK) Cells
- Lymphoid lineage cells but part of innate immune system
- Cytotoxic cells that kill virally infected/malignant cells
- Cytoxicity comes from pore-forming molecules that are inserted into target cell membrane and cytotoxic chemicals that enter the target cell cytoplasm
Describe the roles of key signalling molecules and receptors of the innate immune system
- PAMPs - Pathogen-associated molecular patterns - Molecular motifs commonly found in broad classes of pathogens and absent from humans. E.g. Often glycoconjugates, with lipo-polysaccharides (LPS) present in outer membrane of Gram-negative bacteria.
- PRRs - Pattern Recognition Receptors - Present on innate immune system cells such as macrophages and dendritic cells, recognise PAMPs and initiate response
Describe Signalling and the Humoral Innate Response
- Cytokines - small protein signalling molecules of the immune system. e.g. interleukins, chemokine (Induce chemotaxis), interferons (released by virus-infected cells)
- Acute phase proteins (APPs) humeral factors, can be up-regulated (positive APP) or down-regulated (negative APP) in response to inflammation
- Positive APPs include C-reactive protein (CRP) and complement factors, both of which can function as opsonins, labelling microbes for phagocytosis
Outline the initiation and outcomes of the complement cascade
- Complement/globular proteins work in cascade where one protein cleaves the next to produce active fragments
- 3 initial pathways (classical, alternative, and lectin) that converge with cleavage of inactive C3 protein into active C3a and C3b fragments
- Result of cascade is to form membrane attack complexes, disrupt the cell membranes of pathogenic bacteria
- Outcomes need to know: Inflammation, Opsonisation and phagocytosis, Further Inflammation, lysis of microbe
Outline the different initiations of the complement cascade
- Classical - Involves link with adaptive immune system - Activates cascade via binding of antibody to antigen, activates C1-complex, initiating protein cleavage cascade
- Alternative - Direction interaction of C3 with pathogen surface promotes C3 cleavage
- Lectin - Binding of mannose-binding lectin (protein) to mannose (sugar) on pathogen surface initiates protein cleavage cascade
List the components of the Adaptive Immune system
- Cellular components: B-Lymphocytes, Cytotoxic T-Lymphocytes, Helper T-Lymphocytes, Regulatory T-Lymphocytes, Antigen-presenting cells
- Memory cells - B-Lymphocytes / T-Lymphocytes
- Humoral component: Antibodies (immunoglobulins)
Describe the normal functional of the adaptive immune system
- B-cells secrete antibodies
- Cytotoxic T-Cells (Tc) specifically kill infected cells and some tumour cells
- Helper T-cells (Th) secrete cytokines (signalling proteins that affect other immune cells) + stimulates B-cells
Explain the roles of B-cells in the adaptive immune system
- Activation of B-cells –> Plasma cells
- When correct antigen binds to antigen-receptor on surface of B-cell, cell activated and starts producing and secreting same antibody at high rate
- Antibody produced is specific, only one type of antigen-binding site
Describe the Adaptive Humoral Immunity
Antibody-mediated immunity once released from B cells and into the extracellular fluids:
Antibody binding to antigen can: Block pathogen from causing harm, mark pathogen for phagocytosis (opsonisation), activate the complement system (part of innate immunity
What is meant by multiple antibody binding
Many different antibodies can bind to separate parts fo the same antigen, known as epitopes. Some have higher affinity for antigen than others
Explain the roles of clonal selection in immune responses
B-cells producing right antibody are selected from a huge range of B-cells and activated, requires activated T-cells. Each stimulated B-cell produces a clone of cells via proliferation and diversification. All produce antibody for same antigen. Particular antigen may activate hundreds of different clones
Explain the role of immunological memory in immune responses
Selective stimulation of B-cells recognising the antigen / Activated T-cells selectively expanded resulting in increased immunity due to memory cell production, which can be long-lasting.
Explain the differences between primary and secondary immune responses
- After initial exposure to antigen, small fraction of B-cells will specifically recognise and mount immune response, cells also proliferate and form memory cells.
- Means secondary encounter of body with same antigen will result in immune response faster and stronger
- Concept of immunisation
Describe the antibody classes and their function in immunity
- During immune response, antibody type switches from IgM to IgG ‘class switch’ involves deletion of DNA.
- To produce variety areas of antigen recognised
List the different types of T-cells in the Adaptive Immune System
- Cytotoxic T-cells (Tc) have cell surface protein CD8
- Helper T-cells (Th) have cell surface protein CD4
- Regulatory T-cells (Treg) - Some CD4+ cells
Explain the roles of Helper T-cells in the Adaptive Immune System
- Activate other cells, including B-cells and macrophages, by cell-to-cell contact and secreting cytokines
- TH1 cells secrete cytokines (e.g. interferon-γ) mainly activate virally infected cells, macrophages, other T-cells
- TH2 cells secrete cytokines (e.g interleukins) mainly activate B-cells
Explain the roles of Cytotoxic T-cells in the Adaptive Immune System
- Central to cell-mediated arm of adaptive immunity
- Cells can present antigen on MHCI molecules on cell surface if infected - Recognised by Tc cell, proliferates (Th cells influence this)
- Activated Tc Cells produce pore-forming proteins perforin and granulising, granzymes (proteases) which cause apoptosis of target cell
Explain the role of Antigen-presenting cells in the Adaptive Immune System
- TCR (T-cell Receptor) - αβ heterodimers. Associated with a CD3 complex, involved in cell signalling
- T-cells will not recognise antigens in solution - only peptides ingested, processed, and presented on Major Histocompatibility Complexes (MHCs) by other cells
- T-cell interacts with both antigen and MHC presenting it
Explain the roles of key signalling molecules and receptors of the adaptive immune system.
- Class I MHC Proteins - Present on most cells, recognised by CD8+ cytotoxic T-cells. Peptides derived from cell cytoplasm. Intracellular (virus)
Class II MHC Proteins - Present on antigen-presenting cells is recognised by CD4+ helper T-cells. Peptides derived from ingested material. Extracellular (bacterial) - CD4 and CD8 Accessory Molecules - Bind to non-variable parts of MHC proteins and promote interaction between T-cells and target/presenting cells
What cells do Class I MHC proteins interact with?
CD8+ cytotoxic T-cells - Kill infected cell - CD8 accessory molecule promotes
What cells do Class II MHC proteins interact with?
CD4+ helper T-cells, stimulates helper T-cells, CD4 accessory molecule helps
What are Volatile Acids? How are they excreted?
- Source of H+ in the body from aerobic metabolism and CO2 production
- H2CO3
- Can leave solution and enter atmosphere (‘volatile’)
- Excreted by lungs
What are Non-Volatile Acids? How are they excreted?
- Source of H+ in body from fixed/non-respiratory metabolic processes
- Organic acids such as lactic acid or keto acids may also be formed in certain circumstances
- Excreted by kidneys
Why is Hydrogen Ion Regulation important?
- Alters protein activity, especially enzymes
* Alters binding of other ions e.g. Low [H+] increases Ca2+ binding to albumin
Describe the mechanisms for regulation of body fluid pH
- Buffer systems - Rapid chemical reactions minimising sudden changes in pH, unable to change overall body H+
- Lungs - Can rapidly adjust excretion of CO2
- Kidneys - Slowly adjust excretion of H+ in urine (altering body bicarbonate levels)
Describe the regulation of body fluid pH by the Buffer System
- A buffer - Any substance that can reversibly bind H+
- If H+ added buffer binds it
- If H+ removed buffer releases it
- Rapidly adds or removed H+ to minimise overall changes in [H+] as long as buffer is available
- Limited capacity
What are the 3 Buffer Systems in the Body?
- Bicarbonate (most imp) - extracellular
- Phosphate (intracellular and in urine)
- Protein (mainly intracellular)
Describe the Bicarbonate buffer system
- Most important extracellular buffer
- H+ + HCO3- H2CO3 H20 + CO2 (carbonic anhydrase)
- Connects lung control of [CO2] to kidney control of bicarbonate [HCO3-] in acid-base balance - shows how systems can compensate for each other
State normal ratio of [HCO3-] : [CO2] And The effect of these components on blood pH
- ~20:1 ratio, can be used in Henderson-Hasselbalch Equation
- Increase in PCO2/Decrease in HCO3- = Decrease in pH
- Decrease in PCO2/Increase HCO3- = Increase in pH
- H+ + HCO3- H2CO3 H2O + CO2
Describe how the kidneys contribute to Acid-Base Balance
- Reabsorption of filtered HCO3- to avoid reduction in [HCO3-]
- Excretion of H+ (Production of new HCO3-)
- Both processes rely on ability of kidneys to secrete H+
- Loss of H+ is equivalent to gain of HCO3-
Why is urine usually acidic?
- Kidney control of Acid-Base balance - Must excrete 70-100 mmol/day of H+ from non-volatile acid production
Describe how the Kidneys contribute to the reabsorption and production of HCO3- in the Proximal Convoluted Tubule
- Majority reabsorbed in PROXIMAL CONVOLUTED TUBULE (~85-90%)
- HCO3- can’t be directly transported
- H+ pumped out of PCT via anti-port of Na+ into cell
- Forms H2CO2 with HCO3- in tubular lumen, dissociates into CO2 + H2O
- Transported into tubular cell where carbonic anhydrase converts to H2CO3 HCO3- + H+ again
- HCO3- transported via symport with Na+ out of cell into renal interstitial fluid
- H+ just travelling round in cycle so no net gain or loss in acid-base status despite H+ secretion
Describe how the Kidneys contribute to the reabsorption and production of HCO3- in the Distal Convoluted Tubule
- ~5% filtered HCO3- reabsorbed in late distal/collecting tubules
- Similar mechanism as at PCT - H+ Secretion –> H2CO3 –> CO2 + H2O back into tubular cells –> Carbonic anhydrase converts back to HCO3- into interstitial fluid.
- However, H+ secretion into lumen - Used H+ ATPase Transporters + H+/K+ ATPase Transporters
- Activity can be stimulated by aldosterone and hypokalaemia
Describe how urinary buffers regulate the excretion of acid by the kidney
- Allow sufficient H+ to be excreted in urine + comfort
- Phosphate + Ammonia
- Process of excreting H+ generates new HCO3-. Important as some is consumed buffering 70-100mmol non-volatile acids produced each day
- Can respond to body’s acid-base status
- Decrease in pH stimulates renal glutamine metabolism leading eventually to increased H+ excretion.
- Explains why renal responses are slower than lungs - requires protein synthesis (glutaminase for Ammonia synthesis) /breakdown (Carbonic Anhydrase)
Name the 2 main Urinary Buffers. What are the function of these?
- Comfort and to allow sufficient H+ to be excreted in the urine
- Phosphate and Ammonia
- Monoprotic Phosphate (HPO42-) + H+ H2PO4- Diprotic Phosphate. Relative excess of monoprotic form in tubular fluid lumen, picks up excess secreted H+ in lumen and excretes it in urine.
- Ammonium (NH4+) synthesised from glutamine in PCT cells (via glutaminase) Ammonia (NH3) and Ammonium (NH4+) form buffer pair. Ammonia is eventually secreted in collecting duct in combination with H+, ‘picks up’ excess secreted H+ and excretes it in urine as ammonium.
- Both these processes lead to production of HCO3- as H+ being secreted from cells
Define Acidosis
- Any process resulting in blood becoming more acidic than normal, i.e. lower pH
- Addition of acid +/- Loss of alkali (base)
Define Alkalosis
- Any process resulting in blood becoming more basic (alkaline) i.e. Higher pH
- Addition of alkali (base) +/- Loss of acid
State the differences between Metabolic and Respiratory acid imbalance
- Metabolic acidosis/alkalosis - Primary problem affecting [HCO3-]
- Respiratory acidosis/alkalosis - Primary problem affecting CO2 excretion
- All signify underlying disease
Define Compensation in terms of Acid-Base Balance
- Ratio of [HCO3-] and [CO2] that gives pH, abnormality of one parameter can be compensated to a certain degree
- pH not normalised but minimised changes - towards normal
- In compensated disorders, both [HCO3-] and [CO2] values lie outside their normal ranges (and in same direction, both raised/lower)
Define, explain and recognise cases of Respiratory Acidosis
- Low pH due to increased [CO2], CO2 retention
- Causes: Any disorder affecting lungs; chest wall; nerves; muscles; or CNS leads to inappropriate reduction in ventilation
- Compensation - Slow (days) by kidney to increase production of bicarbonate
Define, explain and recognise cases of Respiratory Alkalosis
- Raised pH due to decreased [CO2]
- Causes: Any disorder that’s leads to increase in ventilation e.g. anxiety, hyperventilation; high altitude
- Compensation: Slowly by kidneys to decrease production of bicarbonate (days)
Define, explain and recognise cases of Metabolic Acidosis
- Low pH due to decreased [HCO3-]
- Causes: Either addition of acid - exogenous (e.g. methanol) of endogenous (e.g. lactic or keto acids) - Failure of H+ excretion or loss of HCO3- (e.g. severe prolonged diarrhoea)
- Anion gap can be used to narrow differential diagnosis
- Compensation: Rapidly by lungs to increase ventilation and thus decrease [CO2]
Define, explain and recognise cases of Metabolic Alkalosis
- Raised pH due to increased [HCO3-]
- Causes: Either addition of alkali; excess loss of H+ (e.g. severe, prolonged vomiting); excess aldosterone e.g. due to dehydration (stimulates H+ secretion in distal tubule)
- Compensation: Rapidly by lungs to decrease ventilation and increase [CO2]
Describe Treatment approach of Metabolic Acid-Base Disorders
- Treat + Correct Underlying problem where possible
- Use substances to neutralise acid/base - Controversial and Senior decision
- Sodium bicarbonate to treat acidosis
- Ammonium chloride for alkalosis (uncommon)
Describe the Approach to Acid-Base Interpretation
- Look at pH first - Normal, low (acidosis), raised (alkalosis)
- Look at [HCO3-] and pCO2 values - If due to pCO2 = primary respiratory disorder. If due to [HCO3-] = primary metabolic disorder
- Look for evidence of compensation - Has other value moved out of its normal range ( in same direction) so as to minimise pH change?
What is typically normal pH range in normal physiological conditions?
7.36 - 7.44
Which law predicts the pressure generated inside an alveolus based on its surface tension and radius?
Laplace’s Law - ‘Pressure within bubble equal to twice the surface tension divided by radius’. Smaller a bubble, the greater the internal pressure needed to keep it inflated.
In which part of the nephron is ammonia buffer produced through metabolic breakdown of glutamine?
Proximal Convoluted tubule
Pulmonary fibrosis involves increased the amount of connective tissue in the pulmonary interstitium including alveolar membrane.
What effect will pulmonary fibrosis have on pulmonary compliance compared to normal?
Decreased pulmonary Compliance
A baby is born prematurely at 28 weeks gestation. Within the first few minutes he develops respiratory distress and reduced oxygen saturations. Which of the following is a key factor in the development of his presentation?
Increased Alveolar surface tension
- As surfactant begins to be produced 24 weeks after gestation - 34 weeks. Preterm babies have immature lungs due to surfactant deficiency. Leads to reduced pulmonary compliance and increased surface tension
What is the equation linking Cross-sectional area and Radius at a given flow
At a given flow, velocity is inversely proportional to cross-sectional area (A) = πr²
What is Normal Cardiac Output at rest?
~5L/min
Outline the Factors Contributing to Turbulent Flow
- Velocity is high
- Viscosity is low
- Tube diameter is high
- Tube branching or irregular surfaces
What is Transmural Pressure
- = P(intravascular) - P(extravascular)
- Intravascular - Pressure fluid inside vessels exerts on inside of wall
- Extravascular - Pressure exerted outside e.g. interstitium
What happens if Transmural Pressure is Positive
- Vessel gets larger, Distends (If distensible)
What is Vessel Capacitance
- Distensibility gives them capacitance
- Will store blood
- The more compliant the more stored
- Veins particularly compliant - Venous system holds 70-80% circulating blood volume
what is the relationship between pH and H+
- pH is calculated used H+ conc in moles per litre
- Inverse relationship between pH and [H+]
- 1 unit pH change is equivalent to 10-fold change in [H+]
