Section 5: Respiratory System Flashcards
What 2 things are essential for efficient exchange
Diffusion distance between air and blood must be small
Surface area over which exchange takes place must be large
Both are achieved in human lungs
Diffusion distance ~0.5µm
Internal SA of lungs ~100m^2
Respiration
The transfer of gas (O2 / CO2) across a boundary
External respiration
The process in the lungs by which oxygen is absorbed from the atmosphere into blood within the pulmonary capillaries, and CO2 is excreted
i.e. air –> blood
Internal / tissue respiration
The exchange of gases between blood in systemic capillaries and the tissue fluid and cells which surround them
i.e. blood - tissues
Cellular respiration
The process within individual cells through which they gain energy by breaking down molecules (e.g. glucose)
Pulmonary ventilation
AKA breathing
The bulk movement of air into and out of the lungs
What is the ventilatory pump comprised of
Rib cage with its associated muscles and the diaphragm
Functional classification of respiratory system
Conducting part/zone
Respiratory part/zone
Structural classification of respiratory system
Upper respiratory tract
Lower respiratory tract
Conducting zone of respiratory system
A series of cavities and thick-walled tubes which conduct air between the nose and deepest recesses of lungs
Warms, humidifies, and cleans air
No gas exchange
Conducting airways
Nasal cavities Pharynx Larynx Trachea Bronchi Some bronchioles
Respiratory zone of respiratory system
Comprises the tiny, thin-walled airways where gases are exchanged between air and blood
Undergoes gas exchange
Respiratory zone - airways
Respiratory bronchioles
Alveolar ducts and sacs
Alveoli
Upper respiratory tract
Nose –> larynx
Less extreme infections
Lower respiratory tract
Trachea –> alveoli
Closer to blood supply –> more extreme infections
Pathway of gases during respiration
O2: Ventilatory pump (air) —external respiration—> left cardiac pump —internal respiration—> cells / cellular respiration
CO2: Cells —internal respiration—> right cardiac pump —external respiration—> ventilatory pump
Purpose of upper respiratory tract
Prepare air for gas exchange:
- Warm –> 37°C
- Clean –> filter
- Wet –> humidify –> 100% saturate with H2O
Nasal cavity - turbinates
Increases surface area of nasal cavity
Turbulence - mixes the air and slows it down
Nasal cavity - vibrissae
Coarse hair filter
Nasal cavity - respiratory epithelium
Pseudostratified columnar ciliated epithelium (filters and humidifies) + goblet cells (source of mucous)
Nasal cavity - seromucous gland
Underneath epithelium
Mucous filter
Water humidification
Nasal cavity
A tall, narrow chamber lined with mucous membrane
Nasal cavity - purpose of wet membrane
Humidifies and warms inspired air
Nasal cavity - surfaces
Medial surface is flat
Lateral surface carries conchae (3 sloping shelves) that increase SA of mucous membrane
Nasal cavity - paranasal sinuses
Air-filled sinuses that open into the cavity
Lighten the face and add resonance to voice
Nasal cavity - olfactory epithelium
Found on roof of cavity
Turbulence caused by sniffing carries air up to epithelium
Axons of olfactory receptor cells lead towards the brain through cribriform plate (perforations in the overlying bone)
Parts of the pharynx
Nasopharynx
Oropharynx - part of digestive system
Laryngopharynx
Pharynx
A vertical passage with three parts, each having an anterior opening
An airway and a foodway - primarily part of the GI system
Epiglottis
An elastic cartilage
Branching: Conducting zone - structures and (generations)
Trachea (0) 1° / Main stem bronchi (1) 2° / Lobar bronchi (2) 3° / Segmental bronchi (3) Smaller bronchi (4-9) Bronchioles (10-15) Terminal bronchioles (16-19)
Branching: Respiratory zone - structures and (generations)
Respiratory bronchioles (20-23) Alveolar ducts (24-27) Alveolar sacs (28)
Branching of airways
One tube will only branch into 2, and it narrows
Branching: 20th generation
~20th generation is where the air should be clean
Infection beyond the 20th generation might become more serious
Windpipe
A tube ~12cm long and as thick as your thumb
Supported by incomplete C-shaped rings of cartilage
Lined with pseudostratified ciliated columnar epithelium
Windpipe - Trachealis muscle
Smooth
Connects the free ends of the cartilage
Contraction narrows the diameter of the trachea
Windpipe - cilia
Transport a mucous sheet upwards to the nasopharynx (mucociliary escalator)
Mucociliary escalator
100-300 cilia per cell
Don’t all move at the same time
‘Mexican wave’
Oesophagus
Sits immediately posterior to trachea
Lies in shallow groove formed by the trachealis muscle
Smoking - mucous
Smoking overstimulates mucous production –> smoker’s cough with lots of mucous by generating huge pressures to move the mucous
Sinuses
Big spaces within our face which are connected
Pathway of respiratory system
Nose –> nasal cavity –> pharynx –> larynx –> trachea –> bronchi –> lungs
Sources of mucous in trachea and bronchus
Goblet cells
Glands
Bronchi - branching and size of cells
As they branch, the epithelia height gets smaller
Goes from pseudostratified columnar to cuboidal to flat squamous cells because need thin layer for gas to diffuse efficiently
Bronchioles
Tubes can keep themselves open
Most air is conditioned - don’t need that much mucous anymore, just need to keep the lining wet
Wall of a bronchiole: Club cells
AKA Clara cells
Not ciliated
Watery secretion –> H2O
Anti-microbial enzymes
Wall of a bronchus: Goblet cells - cilia
Not ciliated
Wall of a bronchiole: Smooth muscle
Controls diameter of tube
Wall of a bronchiole: Thickness
Much thinner than bronchus because we lose structures we don’t need anymore
Bronchodilation and bronchoconstriction
Controls tone of airways
Acute asthma attack
Rapid bronchoconstriction
Treat with bronchodilater (salbutamol / ventolin) - relaxes smooth muscle
Cell types present in alveolus
- Squamous pneumocyte (type I alveolar cells)
- Surfactant cells (type II alveolar cells)
- Alveolar macrophage
Alveolus: Surfactant cells
Prevent collapse of alveoli on expiration –> decreases work of breathing
Repel each other constantly
Work of breathing
Amount of energy required to inspire
Alveolus: Premature babies
< 30 weeks
Have low no of surfactants, so every time they exhale, their alveoli collapse
Can lead to neonatal respiratory distress
The diffusion barrier
AKA blood-air barrier
External respiration
Diffusion barrier: Fibrosis
An increased amount of CT leads to increased distance
Individual becomes hypoxic
Airway: Cartilage
Supports the large airways during inspiration
Doesn’t continue beyond the smallest bronchi
Mucous glands also stop here
Airway: Thickness of epithelium and diameter
Thickness of epithelium decreases as airway diameter decreases
Airway: Goblet cells vs Club cells
Goblet cells secrete mucous in the large airways
Club cells release a serous (watery) secretion in bronchioles
Small airways: Smooth muscle
Have more smooth muscle (in spiral orientation) in relation to their size than large ones
But muscle coat doesn’t continue beyond the smallest bronchioles
Subdivisions of the lung
Primary bronchi: right and left main stem bronchi supplying each lung
Secondary bronchi: lobar bronchi supplying lobes (2 on left, 3 on right)
Tertiary bronchi: segmental bronchi supplying segments of lung (8 on left, 10 on right)
Segment of lung
Each segment has its own air and blood supply
Tumours in lungs
When a localised tumour occurs in the lung, can remove one or more segments containing the tumour without excessive leakage of air or blood from neighbouring segments
Each segment is encased in…
CT
Each segment of the lung is being supplied by…
A segmental (tertiary) bronchus
Pleurae
A smooth membrane that covers each lung
Also lines thoracic cavity in which the lung sits
The 2 membranes are continuous at the hilum
Hilum
The root of the lung
Where the main stem bronchus enters the lung
What separates the pleurae
A thin film of fluid
Allows pleurae to slide past each other without friction
Prevents them from being separated - when thoracic wall moves inward, outward, upward, or downward, lungs must follow
Quiet breathing - ribcage
Movement of ribcage is responsible for ~25% of air movement into and out of lungs
Quiet breathing - inspiration and expiration
Inspiration is active - requires contraction of external intercostal muscles
Expiration is passive - ribcage returns to its resting position without requiring muscular action
External intercostal muscles
Run obliquely between ribs
During exercise, the contraction of them has the effect of lifting the ribs
Breathing during exercise - intercostal muscles
Both sets of intercostal muscles are now active
Externals for inspiration
Internals for expiration
Ribs - structure
Pivot around their joints with the vertebral column
Internal intercostal muscles - structure
Run at right angles to the externals
Internal intercostal muscles - function
When they contract, they drag the ribs downwards
Active contraction only occurs during forceful exhalation
Diaphragm - structure
A dome-shaped platform that forms the floor of the thorax and roof of the abdomen
Lateral margins are muscular - fast-acting skeletal muscle, innervated by the phrenic nerve
Central tendon
Central part of the diaphragm
A thin sheet of CT (aponeurosis)
Diaphragmatic muscle - contraction
Flattens the diaphragm, pulling its central dome downwards
Increases V of thorax –> inspiration
Diaphragmatic muscle - passive relaxation
Allows diaphragm to lift back towards thorax
Reduces thoracic V –> expiration
Diaphragm - quiet breathing
Movement of diaphragm is responsible for 75% of bulk flow of air during quiet breathing (smaller proportion during exercise)
Definition of respiration
To extract oxygen from the air and tgt with the cardiovascular system transport it to respiring tissues
Remove CO2 from respiring tissues and exhaust into atmosphere
Respiratory and cardiovascular system
Works tgt / coupled tgt
If exercising and CO2 doesn’t increase blood flow through lungs, there’s no point as nothing to supply the O2
Evolution of respiration
Increase in:
Size
Distance
Metabolic rate
Respiratory motor nerves
Phrenic motor neurons (C3-C5)
Intercostal motor neurons (T1-L1)
Abdominal motor neurons (T7-L1)
Evolution of respiration - mammals
Mammals are warm-blooded, so need more O2 - require efficiency
Contraction of muscles involved in inspiration / expiration
Must contract them in an ordered sequence - have a sophisticated neural mechanism to do this
Central pattern generator / neural oscillator
Drives neural impulses that descend down the spinal cord to innervate the diff groups of motor neurons
Respiratory motor nerves: Phrenic motor nerves
Branches feed the phrenic nerve (which innervates the diaphragm)
What is the main respiratory muscle
Diaphragm
~70% of inspiration
Respiratory motor nerves: Intercostal motor neurons
Innervate internal and external intercostal muscles
Exist between ribs
Internal vs external intercostal muscles - contraction
Internal - contract during expiration
External - contract during inspiration
Never contract simultaneously
Respiratory motor nerves: Abdominal motor neurons
Innervate the abdominal nerve; rectus abdominus
Resting = little activity
Exercise = abdominal muscles start to contract during expiration - forces expiration –> increase respiratory rate
Rectus abdominus
Expiratory muscle
Only active during active expiration, e.g. cough, retch, laugh
Respiratory motor neurons: Respiratory rhythm
LMNs don’t generate respiratory rhythm - in isolation from the brain, can’t produce the breathing needed
Generated in UMNs in brainstem
High cervical lesion in spinal cord
Breathing stops because generator for synchronisation for inspiration and expiration is generated in the brainstem
Diaphragm - structure
Shaped like a parachute
70% of inspiratory effort is produced by…
Diaphragm contraction
Diaphragm and ribs - contraction
Diaphragm contracts downwards (flattens) and moves outwards. Doms back up when expiring
Ribs move upwards and outwards
Thoracic cavity - inspire
Thoracic cavity of chest gets bigger in 3 dimensions when you inhale
What does expiration rely on
Elasticity of thorax and lungs to bring diaphragm back to resting state
At rest, this is passive - no energy required
Inspiration is always ___
Active
Respiratory cycle
The inspiratory and expiratory parts we undergo when we’re breathing
From one period of inspiration to the next period of inspiration
Parts of a respiratory cycle
2 parts:
Inspiration (active)
Expiration (passive)
How much air will an average person at rest breathe in
Half a litre of air
Over the course of the day, an average person breathes in how much air
~8,500 litres
Breathing - voluntary?
Kind of voluntary - can control, but is also automatic
Tidal volume AKA
Tidal breath
Pleura membranes
Parietal pleura - runs along outside of chest wall
Visceral pleura - runs around lungs
What is found between the pleura membranes
A pleural cavity filled with fluid
Ppul
Pulmonary pressure
Pressure within airways of lungs
Ppl
Pleural pressure
Pressure from pleural cavity
Why does air move into lungs
Before its moving from an area of higher (atmosphere) to lower (lungs) pressure
Inspiration - pressure
During inspiration, you create an area of lower pressure relative to atmosphere within airways of lungs so air is drawn in
Respiratory cycle - atmospheric pressure
Taken as zero
Respiratory cycle - steps
Before you take your next breath, it’s always -3cm of water relative to atmospheric P - means you have -ve pressure around your lungs
-ve pressure –> lung adheres to inside of chest - if chest wall moves, lung follows –> lung inflates in 3D
When you inspire, Ppl becomes more -ve –> pulmonary P also becomes -ve relative to atmosphere
When you expire, Ppl becomes less -ve –> P within airways become +ve relative to atmospheric –> air moves from lungs to atmosphere
Respiratory cycle: What causes air to move from an area of higher to lower pressure into lungs
The -ve pulmonary pressure within airways relative to the atmosphere
Respiratory cycle: Why is Ppl important
Initial -ve value of Ppl essential to prevent lungs from collapsing
So, Ppl either becomes more -ve or less -ve, never becomes +ve
Pneumothorax
Wounded rib cage by a thoracic puncture wound –> lung moves away from wall and deflates
Air rushes into chest
Loss of -ve pleural pressure
Pneumothorax - treatment
Reinflate the lung by repairing the puncture wound and reinstating the -ve pressure around the lungs
Spirometer - structure
External floating drum (upside down) sits in an inner cylinder of water
Inner cylinder is supported by pulleys, a small wire, and a counterbalancing weight. Also has a tube that allows you to access the air in the floating drum
Spirometer - mouthpiece
Attached to tube of inner cylinder
When you breathe through the mouthpiece, can push the floating drum up and down - can measure respiratory V and capacity
Respiratory volume vs respiratory capacity
Respiratory V is measured
Respiratory capacity is calculated (often combining 2 or more Vs)
Inspiratory reserve volume (IRV)
The amount of extra inspiration you can do above a normal tidal breath
Expiratory reserve volume (ERV)
The max amount of air you can blow out of your lungs after a normal expiration
May need these reserve Vs during exercise
Functional residual capacity (FRC)
Resting point of lung
After expiration just before you take your next breath in
Residual volume (RV)
The V of air in your lungs that you can’t blow out because small airways in lungs will collapse due to expiratory exhalation force around lungs - left with a pocket of air in alveoli
Total lung capacity = ?
VC (can measure) + RV (can’t measure)
Average number of breaths per min for an adult
~12 breaths per min and 500mL per breath
Respiratory volume: What is V(T)
Tidal breath
Respiratory volume: f
Respiratory frequency
Respiratory volume: V(E) with dot on top of V
Minute ventilation
= V(T) x f
= 0.5 x 12 = 6 L/min
Also = V(A) + V(D)
Respiratory volume: What does the dot above the V on V(E) indicate
Indicates it is a time derivative
Hyperventilation vs hypoventilation
Hyper is > 6L/min
Hypo is < 6 L/min
Respiratory volume: V(A) with dot on top of V
Alveolar ventilation
= V(E) - V(D)
= (0.5 - 0.15) x 12 = 4.2 L/min
Respiratory volume: V(D) with dot on top
Dead space ventilation
Anatomical dead space
Approx 150mL - doesn’t go to alveoli, so doesn’t contribute to ventilation
~2.2 mL/kg
Alveolar ventilation allows you to understand…
Gas exchange
Anatomical dead space is found where
In conducting space/zone - full of air not being used for gas exchange
Calculating total lung capacity - process
Connect spirometer to subject and fill it with enough gas that doesn’t go into bloodstream (stays within lungs, e.g. He)
Open valve and let equilibration occur - will be more dilute because now have V of both spirometer and lungs
Calculating total lung capacity - V2
We know conc and V of spirometer, so can calculate V2 (total lung capacity)
Calculating total lung capacity - calculation steps
V2 = V1(C1-C2) / C2
V1: initial volume in spirometer
C1: initial conc of helium in spirometer
C2: helium conc after equilibration
Residual V = TLC (or V2) - vital capacity
Testing lung health - types of values
FEV1: Forced expiratory volume in 1 sec
FVC: Forced vital capacity, usually less than during a slower exhalation. Total amount of air you can blow out
Testing lung health - normal values
FEV1 = 4.0L FVC = 5.0L
FEV1/FVC = 80%
Testing lung health - ratios
Tells physician what type of respiratory problem someone has
Testing lung health - asthma
Both FEV1 will be smaller than normal
FVC may be normal
Recoil force consists of…
Elasticity of the lungs
Surface tension in the lungs
What is recoil force
The combined forces that allow the lungs to deflate and push air out of airways into the atmosphere
Elasticity
Ability to recover original size and shape after deformation
Allows for lungs to change their volume dramatically
Parenchyma
A matrix in the lungs full of tubes, e.g. airways, vessels, alveoli
Holds the lung together by natural elastic fibres and collagen
Lungs - elastin
Allows lung to inflate and deflate
Lungs - collagen
Provides structure
Elastin and collagen - inspiration and expiration
As you go from expiration to inspiration, the intrinsic fibres of elastin and collagen get stretched and pull the tubes open
Radial traction
An important mechanism through which the lungs can deflate - a force that keeps the lungs open
To do with parenchyma - as inspiration takes place, traction increases
Compliance = ?
1/elasticity
or
change in V / change in P
What is compliance
How easy it is to blow the lungs up and how far they stretch
What is a compliant lung
Easy to inflate and needs little pressure
What is surface tension
The enhancement of intermolecular attractive forces at the surface
Due to the surface (at a liquid-gas interface) having no neighbouring atoms above –> exhibit stronger attractive forces upon their nearest neighbours on the surface
Where is the liquid-gas interface found in the lung
In each alveolus
Gas comes into the alveoli, and membrane of alveoli has a thin film of liquid
We have ______ alveoli
~300 million
Laplace’s law - equation
P = 2T / R
Laplace’s law - alveoli
Alveolus has greater pressure than atmosphere, i.e. a +ve pressure that’s trying to collapse the alveolus, known as collapsing pressure
What does surface tension contribute
Contributes a force for deflating the lungs
Alveoli radius and pressure
Alveoli of diff radii will affect the collapsing pressure that is generated
Why does the lung have cells that secrete surfactant
Collapsing pressure generated would oppose the force required to inflate the lung quite dramatically, so lung secretes surfactant
Surfactant
Like a soap - reduces intermolecular forces and surface tension so lungs become more complacent
Must be moderated because it’s quite a strong force
Compliance relationship of the lung
Compliance (P-V curve) has a fairly linear relationship
But there are some diseases that can affect this relationship –> detrimental effect on how they breathe
Chronic obstructive pulmonary disease (COPD) - compliance
Lungs become more compliant because need less pressure change to produce the same V
Chronic obstructive pulmonary disease (COPD) - individuals
Typically found in someone who smokes cigarettes
Chronic obstructive pulmonary disease (COPD) - lungs
Hyperinflated lungs - don’t properly deflate
Flattened diaphragm
If too hyperinflated, have little ability to inflate their lungs since already somewhat inflated –> rapid and shallower breaths to compensate
Degrades elastin
Fibrosis - compliance
Decreased compliance so need more energy to inflate lungs
Fibrosis - risk factors
Can occur due to air pollutants
Fibrosis - lungs
Caused by an increase in collagen in lungs --> stiff lung Deflated lungs Mid-sternal space wide Fluffy areas with fibrotic tissue Speckled; white splotches
The last air you breathe in is…
The first air you breathe out, so O2 of air you breathe out will be similar to atmospheric O2
The last air you breathe out (at end of your exhale)… (O2)
It will have a significantly lower amount of O2 (~17%) because it originates further down your airway
Highest point of resistance in respiratory zone
Upper airway (trachea) because X-sectional area of one trachea is less than that of ~300 million alveolar ducts
Airflow at higher vs lower points of resistance
High R = less air flow = turbulent
Low R = high air flow = slow and laminar, unidirectional = good for gas exchange
Physical factors controlling airflow
If start by blowing out all the air in our lungs, the airways are quite narrow / high R
As you begin to inhale maximally, the radial traction starts to pull open the airways until TLC
Smooth muscles of bronchioles are covered in…
Receptors sensitive to nerves and hormones which are constantly modulating the diameter of the bronchioles
ANS control of airway smooth muscle
Parasympathetic nerves: Originate from brainstem Contained within the vagus nerve Bronchoconstriction ACh acts on muscarinic receptor
Sympathetic nerves:
Originate from levels of the spinal cord
Bronchodilater
NE acts on beta-adrenoceptors
Asthma: What is salbutamol
A beta-adrenoceptor agonist
Asthma: Inhaler
Contains salbutamol which mimics sympathetic NS activity
Acts on beta-adrenoreceptors on the smooth muscle in bronchioles to make them relax
Instant relief because drug goes directly where you want it to go
Targeting drugs in lungs
Can target your drug directly where you want it to go
Control of airway diameter and resistance - bronchioles - nerve fibres
Each bronchiole has nerve fibres that are stretch-sensitive
When bronchioles dilate during inhalation, it stretches mechanoreceptors –> send signals into brain
Hering-Breuer Inflation reflex - Mechanoreceptors
Nerve fibres mechanically sensitive to distortion/inflation through the vagus nerve into the brainstem, which connect to the sympathetic NS (dilation)
Also terminates inspiration
Pulmonary system - arteries
Blue
Feed alveoli
_______ are wrapped around the alveoli
Capillaries
Pulmonary system - veins
Bright red
Full of oxygenated blood to carry back to the heart
Pulmonary vs systemic pressure
Pulmonary: 22/10 mmHg (mean 16 mmHg)
Systemic: 120/80 mmHg (mean 93 mmHg)
Mean pressure = ?
SA of bottom third of triangle
DP + (1/3 x PP)
Where PP = SP - DP
PP = pulse pressure SP = systolic pressure DP = diastolic pressure
Pulmonary circuit - high or low pressure
Low pressure, so blood from right ventricle comes here
Complete circulation - time
~25s
Where does blood to the pulmonary vascular bed originate from
The right ventricle
Tracheobronchial circulation - contamination
Pulmonary vein carries oxygenated blood, but is contaminated by blood from the tracheobronchial circulation that bypasses the lung (‘anatomical shunt’)
Two pulmonary circulations
One goes to alveoli
Other goes to tracheobronchial tree
Tracheobronchial tree - origin
Comes off aorta
What does the tracheobronchial tree receive blood from
Systemic circulation / aorta
What does the tracheobronchial tree innervate
Trachea, bronchus and bronchioles
Mean pulmonary artery pressure
16 mmHg
Pulmonary artery, pulmonary capillaries and left atrium pressure
As pulmonary artery divides into smaller arteries and arterioles, the pulses become smaller - reduced R
Eventually the pulses fade at the pulmonary capillaries where blood flow is continuous/constant (not pulsatile)
Sheet blood flow around alveoli
Capillaries are so dense that their walls touch each other, most of which vanish
Results in a sheet flow of blood interspersed by an interstitial tissue that pulls the capillaries tgt
Sheet blood flow around alveoli - side walls
Erode away to form a flatter texture –> allows blood to be in more contact with the alveolar membrane
Flow of blood in alveoli
Laminar (smooth)
Pulmonary artery pressure and resistance
Increase in pulmonary artery pressure = decrease in pulmonary vascular resistance
Due to distension and recruitment
Opposite of systemic circuit
Factors controlling blood flow in lungs
Physical
Hypoxia
Factors controlling blood flow in lungs: Physical
Since blood vessels are attached to lung parenchyma, physical or passive mechanisms related to lung V alter size of vessel diameter
Factors controlling blood flow in lungs: Hypoxia
A decreased O2 causes vasoconstriction via a direct effect
Limits blood flow to poorly ventilated alveoli
Hypercapnia also does this
Hypoxemia
Decreased oxygen level
Distension and recruitment
Distension: compliance / wider arterioles
Recruitment: more vessels (that were closed) now open –> resistance falls
Pulmonary oedema
Where P in lungs gets too high –> fluid from capillaries is pushed out –> starts to fill up alveoli with interstitial fluid –> increases distance of diffusion of gases between blood and air
Prevented by keeping P low, and if it does increase, resistance decreases through distension and recruitment
When does hypoxic vasoconstriction occur
If there is an inflammatory response
What does hypoxic vasoconstriction result in
Increased R to airflow due to build up of mucous and fluid
Air follows pathway of least R, so will go into alveoli with wider duct
Hypoxic vasoconstriction: Constricted alveoli
Partial pressure of constricted alveoli reduces –> hypoxic
Causes constriction of local arterioles feeding this alveolus because would not be optimal to send blood to alveoli with low oxygen - known as a physiological shunt as its redirected to alveoli with lots of oxygen
There is better ______ at the base of the lung
Perfusion
What is the regional variation in blood flow due to
Gravity - restricts the height blood can be pumped (i.e. hydrostatic pressure)
What does hypoxic vasoconstriction increase
Increases dead space because the alveolus can no longer undergo gas exchange
Does hypoxia always cause vasoconstriction
Only in the lungs - in other parts of the body it causes vasodilation
Which part of the lung has highest blood flow
Bottom of lung has more blood flow than top
At top, there’s hardly any blood flow when you’re upright and at rest - due to gravity
HP
Hydrostatic pressure
P(v)
Venous pressure
Driving force for blood flow
P(a)
Pulmonary blood arterial pressure
P(A)
Alveolar pressure
Lung - zones
Zone 1: Top of lung where HP is lowest so is poorly perfused P(A) > P(a) > P(v)
Zone 2: Middle of lung, pressure sufficient to open capillaries through the alveoli P(a) > P(A) > P(v)
Zone 3: Base of lung where HP is greatest so is best perfused P(a) > P(v) > P(A)
Form a continuum
Gravity and lung size
Gravity is only a problem in animals and humans that are upright because gravity has a greater effect if you have larger lungs
What does a high alveolar pressure cause
Alveolar pressure squashes down the vessel and prevents blood from flowing, e.g. in zone 1
Parts of the lung - ventilation
Much better air ventilation at lower part than upper part of lung
The bottom of the lung is better…
Perfused and ventilated
Oxygen levels in lung just before inspiration
Lots of well-oxygenated blood at top of lung
Low levels of oxygen at bottom of lung because lots of blood flow which takes up the oxygen
Ideal vs actual ventilation-perfusion ratio (VA/Q)
1; perfectly matches perfusion with ventilation
i.e. alveolar ventilation divided by CO
In reality, this ratio is 0.8
Perfusion = ?
Q = CO = HR x SV = 5 L/min
Disease states: Pulmonary hypertension
Right heart failure
Hypoxia = vasoconstriction
Causes oedema
Causes increase in hydrostatic P of pul cap - known as pulmonary oedema
Diffusion distance for O2 increases –> reduces efficiency of gas exchange –> breathlessness
Disease states: Pulmonary oedema
Left heart failure - blood remains in left ventricle –> congestion –> increases pulmonary artery P –> oedema –> breathlessness - dyspnoea, particularly on exhaustion
Systemic hypoxia
Factors regulating movement of gas across the respiratory surface
Area Thickness of tissue Partial pressure differential across tissue Solubility of gas in blood Molecular weight of gas
Factors regulating movement of gas across the respiratory surface: Area
Each alveoli ~0.3mm in diameter
In spherical, SA = 50-100 m^2 and V = ~4L
Factors regulating movement of gas across the respiratory surface: Thickness of tissue
Only ~0.5µ alveolar membrane that separates blood from outside world
Contains surfactant, epithelial layer, interstitial layer, BM, endothelial cell
Factors regulating movement of gas across the respiratory surface: Partial pressure differential across tissue
O2 from outside to inside: 60 mmHg
CO2 from inside to outside: 6 mmHg
Important for movement of gases from higher to lower areas of conc
Factors regulating movement of gas across the respiratory surface: Solubility and molecular weight of gas
Solubility more important than MWt of gas
CO2 25x more soluble in blood than O2 and diffuses 0.86x faster than O2
But release time of CO2 from haemoglobin slower than O2, so balanced overall
Factors controlling rate of rise of partial pressure of a gas in blood
Diffusion limited:
Includes rxn time for bonding with haemoglobin
e.g. CO
Perfusion limited:
Limit is the blood flow
e.g. N2O and O2
Factors controlling rate of rise of partial pressure of a gas in blood: Increasing uptake for a perfusion limited gas
Can increase uptake if blood flow is greater
If you start exercising and need more O2, can increase blood flow to lungs and pick up oxygen
Amount of time spent by RBC through the alveolus
Only spends 3/4 of a second through the alveolus
How long does it take for blood to be saturated with oxygen and N2O
Within 1/4 of a second because diffusion is v quick
CO rate of uptake
Very slow - if breathing it for a long time, will accumulate lots of CO
Diffusion limited - doesn’t bind v quickly to blood and takes a long time to cross the alveolar membrane
CO poisoning
Takes a long time to get the CO off the haemoglobin molecule that it’s taken up - binding is slow
Haemoglobin preference
Has a preference for CO over O2, so CO bounces the O off the haemoglobin –> extremely hypoxic
How is oxygen transported in blood
Binds with haemoglobin (major pathway)
Dissolves in solution
Haemoglobin (Hb) molecule - haem moiety
Each α and β polypeptide chain contain a binding site called a haem moiety - 4 within a Hb molecule, each of which can bind to a single oxygen
Haemoglobin (Hb) molecule - allosteric effect
When first molecule of O2 binds onto a haem moiety, it twists the molecule to expose the next haem moiety etc.
This process is called cooperative binding
Where is Hb contained within
Erythrocytes (RBCs)
Why are RBCs important
Concentrates Hb Concentrates enzymes (e.g. carbonic anhydrase)
What would happen if we didn’t have RBCs
Blood would be really think and difficult to pump around the body
RBCs - structure
No nucleus
Biconcave - allows it to squeeze through capillaries at branch points
Haemoglobin (Hb) molecule - binding of oxygen molecule
First molecule of O2 that binds to Hb molecule takes longer than second, which takes longer than third, then fourth
Oxygen dissociation curve: Relationship
Sigmoidal relationship
Due to cooperative binding
Oxygen dissociation curve: Systemic veins
Lower affinity for O2 at lower P(O2)s
Encourages O2 release at tissues
Oxygen dissociation curve: Systemic arteries
Higher affinity for O2 at higher P(O2)s
Encourages O2 uptake at lungs
Oxygen dissociation curve: Percent of O2 unloaded by haemoglobin to tissues
~25% saturation
i.e. as you move form higher to lower P(O2), there’s an unloading O2; the Hb can’t be saturated as much because it loses some of its affinity to bind oxygen at lower pressure
Oxygen dissociation curve: Affinity at alveoli
Affinity must be strong when it goes back to alveoli to pick up oxygen - want maximal affinity in lung
Deoxyhaemoglobin and oxyhaemoglobin
Form of Hb without oxygen Hb4 + O2 --> Hb4O2 Hb4O2 + O2 --> Hb4O4 Hb4O4 + O2 --> Hb4O6 Hb4O6 + O2 --> Hb4O8 - oxyhaemoglobin (fully saturated)
CO2 from tissues
CO2 + H2O H2CO3 H+ + HCO3-
This H+ then goes into this reaction:
Hb4O8 + H+ Hb4 + 4O2 –> to tissues
Hb affinity - acidity
In an acidic environment, Hb has less affinity for O2
Tissues vs lungs - oxygen
At tissues, more CO2, lower pH –> O2 is released
At lungs, less CO2, higher pH –> O2 is taken up
What is one of the main reasons haemoglobin loses its affinity for oxygen
The acidity produced from H+ (reduction in pH) at level of tissues
Total oxygen conc in blood = ?
Oxygen bound to Hb + oxygen dissolved in plasma
Amount of oxygen dissolved in plasma
~0.5 mL / 100mL of blood
Amount of oxygen dissolved in plasma at 100% oxygen
Increases oxygen in plasma up to ~2mL / 100mL because you increase the diffusion gradient between the alveoli and the blood
Anaemia
If individual lost half their blood, it reduces the amount of oxygen content in blood by half (both arterial and venous)
But if look at blood saturation, remains at 100% because Hb that remains can still fully load up with O2
Oxygen dissociation curve: Bohr shift
For a given PO2, more oxygen is given up
Due to increased CO2, H+, temp, DPG –> lower affinity of Hb for O2 in venous blood
e.g. at tissues
Oxygen dissociation curve: Leftward shift
For a given PO2, oxygen sat is increased
Due to reduced CO2, H+, temp, DPG —> increases affinity of Hb for O2 in venous blood
e.g. at lungs
Oxygen dissociation curve: Fetal haemoglobin
Higher affinity for oxygen at a given level of PO2
Helps movement of oxygen across placenta to fetus
Oxygen dissociation curve: What happens if fetal Hb doesn’t have higher affinity for oxygen
It wouldn’t be able to draw the oxygen from the mother’s blood into its own
Oxygen dissociation curve: Myoglobin
Large affinity for oxygen
Stores O2 in body, particularly in skeletal muscle, where it can be used under conditions of low O2 –> releases this O2
How is CO2 transported in blood
Dissolves in solution (CO2 aq)
Chemical in form of HCO3-
Combines to amine groups (NH2)
As H2CO3 and CO3- ions
CO2 vs O2 solubility
CO2 solubility in blood is 20x higher than O2
CO2 transport in blood - %
Plasma 70%, RBCs 30%
CO2 transport in blood: Slowly vs rapidly formed bicarbonate
Slowly formed occurs without an enzyme in plasma (5%)
Rapidly formed occurs with an enzyme in RBCs (20%)
Most bicarbonate in the plasma is formed by…
An enzyme called carbonic anhydrase
CO2 transport in blood: Chemical in form of HCO3- - equation
CO2 + H2O H2CO3 H+ + HCO3-
Where is carbonic anhydrase found
In RBCs
CO2 transport in blood: Amine groups - equation
CO2 + R-NH2 R-NHCOO- (carbamino protein) + H+
where R can be Hb
__x more Hb than any other plasma protein
4
What does Hb have greatest affinity for
Greater affinity for CO2 than other plasma proteins
Hb - buffer
Acts as a buffer to maintain pH
Essential for optimal running of enzymes, e.g. carbonic anhydrase
CO2 dissociation curve: what does it depend on
P(CO2)
CO2 dissociation curve: shape
Linear over physiological range of P(CO2)
Very steep - highly sensitive
CO2 dissociation curve: saturation
No saturation as CO2 is v soluble in plasma
CO2 dissociation curve: Greater affinity for CO2 when pH is _____
Lower
CO2 dissociation curve: _____ blood has greater affinity for CO2
Venous
CO2 dissociation curve: Haldane effect
The difference between venous-arterial blood
Enhances unloading of CO2 from tissues into blood
CO2 dissociation curve: Haldane effect - PO2
Lower PO2 –> greater affinity for CO2 (tissues)
Higher PO2 –> reduced affinity for CO2 (lungs)
Hypoxia
Low levels of oxygen
Anoxia
No oxygen
Asphyxia
Deprived of oxygen
Hypercapnia
High CO2
Hypocapnia
Low CO2
Hyperventilate
Excessive breathing
Decreases PCO2, increases PO2
Hypoventilate
Shallow breathing (inadequate) Increases PCO2
Ischaemia
Inadequate blood supply to an organ
Apnoea
No breathing
Dyspnoea
Sensation of breathlessness
Fainting
An important mechanism because it puts your brain at the same level as your heart –> less effect of gravity
What are chemoreceptors
Blood gas detects that control breathing
Types of chemoreceptors
Peripheral chemoreceptors - located near major blood vessels
Central chemoreceptors - located within medulla
Main peripheral chemoreceptor
Carotid body chemoreceptors
Location of carotid chemoreceptors
Located at bifurcation of common carotid artery in neck
Sits in the crux where internal and external carotid arteries originate
Close to baroreceptors (but not the same)
Carotid chemoreceptors - sinus nerve
Joins the glossopharyngeal nerve, then to medulla (brainstem)
Location of central chemoreceptors
3 ‘chemo-sensitive’ regions on the ventral surface of the medulla oblongata
What stimulates peripheral chemoreceptors
Hypoxia (reduced PO2) Hypercapnia (increased PCO2) Haemorrhage (low O2) Acidosis Increased sympathetic activity Sodium cyanide (experimental tool)
Acidosis
Decreased blood ph
Peripheral chemoreceptors - response time
Fast - within a breath
What stimulates peripheral chemoreceptors - sodium cyanide
Temporarily switches off ETC
Similar to low O2
Central chemoreceptors - response time
Slow
~30s
Because there is limited carbonic anhydrase in CSF
Central chemoreceptors: CO2
Can cross blood-brain barrier
Central chemoreceptors: Blood-brain barrier
Effectively the endothelial cells that line the capillaries
Central chemoreceptors: CSF
Within the CSF there is some carbonic anhydrase
Central chemoreceptors: Neural cells
Very close to CSF, so if you apply acid, they become v activated and stimulate breathing
Central chemoreceptors: Brain is intrinsically sensitive to ___
H+
What predominantly simulates central chemoreceptors
H+ ions
Central chemoreceptors: H+
Can’t cross blood-brain barrier since charged
Central chemoreceptors: CO2 vs O2
Only respond to CO2 (H+) - don’t respond to low oxygen
Ventilatory response to hypoxia involves what chemoreceptors
Peripheral chemoreceptors only
Ventilatory response to hypoxia
As PO2 is reduced, minute ventilation increases (slowly then dramatically) until peak
Ventilation starts to slow due to central depressant effect within brainstem
Cells within brainstem that are depressed eventually stop functioning –> depresses breathing –> apnoea
Ventilatory response to hypoxia - gasping
Individual gasps a number of times
The last attempt to auto-resuscitate
Ventilatory response to hypercapnia involves..
Mediated by:
Central chemoreceptors 80%
Peripheral chemoreceptors 20%
Ventilatory response to hypercapnia - slope
Steep slope - exquisitely sensitive to CO2
Increased PCO2 = steep increase in minute ventilation
Ondine’s curse
No central chemoreceptors means you can die in your sleep
Very important for breathing
What allergens are associated with asthma
Pollen
Dust
