Respiration Flashcards
How does the airway change as it goes deeper into the lung (3)
Becomes
Narrower
Shorter
More numerous
How is the airway divided anatomically
24 regions
Numbered 0-23
How are the 24 generations divided
The first 17 generations are the conducting zone (anatomical dead space)
Generations 17-23 are the respiratory zine
What is the role of the conducting zone (3)
To warm and humidify the air inspired
To distribute air into the depths of the lung
To serve as a bodily defence against dust and bacteria
Describe the structure of the conducting zone
How does this lead into the respiratory zone
Trachea —> main bronchus —> lobar and segmental bronchi —> terminal bronchioles
—> respiratory bronchioles —> alveolar ducts —> alveoli
What is the smallest airway that does not allow gas exchange
Terminal bronchioles
Which parts of the airway are subject to thoracic pressure
How do they not collapse from the increased intrathoracic pressure during forced expiration
First 4 regions
They have cartilage arranged in U shaped rings
How does the arrangement of cartilage change through the airway
Initially in U Shaped rings on first 4 regions
Then becomes plates of cartilage in the lobar and segmental bronchi
It disappears in the bronchioles
How are bronchiolar airways maintained
By elastic connections to the parenchyma
What is the conducting zone supplied by
The bronchial circulation
What is the volume of the respiratory zone
~2.5 to 3 litres
How fast do RBC flow through pulmonary circulation
Less than a second
How does inspired air enter the lungs
Inspired air flows down by bulk flow, but the increased area of the conducting zone reduces the forward velocity of airflow
Give an advantage of the reduced airflow velocity to the alveoli
Dust and pollutants usually settle out before the alveoli
What is the driving force of oxygen/ CO2 exchange
Pressure gradient across the alveoli/ blood interface
Give the equation for Net Flux
(C1-C2) x (area/thickness) x D
How many alveoli in an adult human
300-500 million
How close can blood come to the air in the alveoli
0.5μm
How does the body manipulate Fick’s law to maximise diffusion
Large alveolar surface area and close association to the capillaries
Give 2 equations for flow for respiratory physiology
Flow = Δpressure x K
Or
Flow = Δpressure/ resistance
Why is the equations for flow important for respiration
A pressure gradient must be produced when breathing
Describe the thoracic pleura
Visceral pleura encases the lungs and is separated from the parietal pleura by a ~10μm thick layer of fluid
What determines the volume of the thoracic cavity
What is normal intrapleural pressure
The balance of the inward elastic recoil of the lungs and the outward elastic recoil of the chest wall
-5cmH2O
How is a pressure gradient created in the lungs
Increase thoracic volume and decrease intrapleural pressure
This is done by contraction of the diaphragm and the movement of the intercostal muscles, widening the thorax and raising the sternum
What happens if the lung is punctured
Pressure within would equilibrate with the atmosphere and the lungs would collapse due to their inward elastic recoil. This is pneumothorax
What stops both lungs collapsing in a right pneumothorax
The mediastinal membrane divides the thoracic cavity into 2 airtight compartments
What is eupnea
Quiet respiration
A passive process whereby Respiratory muscles relax, allowing the elastic potential of the lungs to recoil.
Does eupnea always occur
No
During exercise other muscles are recruited, such a abdominal muscles helping to raise the diaphragm
What are trans mural pressures
Pressures across a wall
How many trans mural pressures are there In The basic thoracic cavity
How are they all worked out
Transpulmonary
Trans chest wall
Trans total system
The pressure differential of the inside minus the outside
What is trans pulmonary pressure in normal humans
The greater the trans pulmonary pressure the ____ the lungs expand
always Positive
More
How do diaphragmatic contractions and thoracic cage expansion affect pleural pressure and trans pulmonary pressure
Decrease from -5 to -8cmH2O
Trans pulmonary increases
What is distending pressure
The pressure that keeps the lungs inflated
Why does airflow at the end of inspiration stop
Alveolar pressure equals atmospheric pressure
Why does air flow into the alveoli basically
Alveolar pressure is greater than atmospheric pressure and air flows from the lungs to the mouth until alveolar pressure= atmospheric pressure
When is capacity used for the spirometer
When a lung volume can be broken down into two or more smaller volumes
Are gases collected by the spirometer at body temperature
Nope
How is water vapour an imperfect gas
It changes its state from vapour to liquid with temperature changes within the physiological range
Give the ideal gas equation for respiration And the units
PV=nRT
P=mmHg
V= litres
T=K
What is R in the respiratory ideal gas equation
Give the units
62.36mmHg x L x mol-1 x K-1
How many litres does one mole of gas occupy at STPD
22.4
What is the relationship between a constant amount of gas at 2 different sets of temperature and pressure defined by
P1 x V1. P2 x V2
———— = ———-
T1. T2
How to calculate the new volume of saturated gas using the PV=nRT equation
Use P1V2/T equation
Use Table to find PH2O at new temperature and subtract that from the original partial pressure.
Input this new value into P1V1/T1=P2V2/T2
What is BTPS
Body temperature and Pressure standard
The physiological conditions within the body
What is the partial pressure of O2 in alveolies
13.2%
What is the partial pressure of CO2 in alveolies
5.3%
What is the partial pressure of N2 in alveoli
75.4%
What is the partial pressure of Water in alveolies
6.2%
Why do PCO2 and PO2 vary around the mean
Breathing is intermittent
A small amount of air is taken into the lungs with each breath relative to the volume of gas that is not exchanged (FRC)
What is indicator dilution technique used for
To determine residual volume and functional residual capacity
What is physiologic dead space
Alveolar dead space + anatomic dead space
Give typical breathing frequency and tidal value at rest
12 breaths/ min
500ml
What is the total normal inspired ventilation rate (Vi)
How much tidal volume actually gets to the alveoli for exchange
6 L/min
350ml
Is dead space constricted to the conducting zone
No
Doen alveoli have no blood flow or may have reduced blood flow
How much dead space is there in a seated individual weighing 170lb
170ml
Dead space ~ person’s weight in pounds
What is VE
Expired minute volume
VE= Vt x breathing frequency
What assumption is VE based on
Volume inspired=volume expired
Not quite true as our western diet means less CO2 is produced than O2 consumed
What is the volume of fresh air reaching the alveoli known as
Give the equation
Alveolar ventilation
Va=(Vt-Vd) x f
What is Vd
Volume of dead space
How can alveolar ventilation be estimated
From the volume of CO2 expired ina given time and the fractional concentration of CO2 in alveolar gas. All the expired gas must have come from the alveoli
Give the equation for volume of CO2 expired per minute
Va x FACO2
(Where FA CO2 is the fractional concentration of CO2 in alveolar gas
Va=?
Volume CO2 expired/ min
————————-
Fractional concentration of CO2
How is FA CO2 obtained
Sampling end tidal volume
What does VA=
To convert to correct units
Give units of each
Va(L/min)=(VE CO2 / PA CO2) x K
VE CO2: (ml/min)
PA CO2 (mmHg)
K: (mmHgx L/min
Va is at _____ and VE CO2 is at ____
BTPS
STPD
What is the conversion constant usually for Va
0.865 mmHg xL/ml
How are Va and PACO2/ FA CO2 relates
Inversely proportional
How does PA CO2 relate to CO2 in arterial blood
In equilibrium
How does hyperventilating affect P CO2 in arteries
Halves arterial P CO2
How does hypoventilation affect arterial PO2
Doubles arterial P CO2
How is Pa CO2 monitored by an anaesthetist
Using an infrared CO2 analyser on end tidal expiration
If a patient under anaesthetic had a PA CO2 of 80mmHg what would the anaesthetist do
Why
Double ventilation
Ratio of VE CO2/ Va is twice normal ratio
How does exercise affect VE CO2 and therefore Va
If VE CO2 Increase 5x, alveolar ventilation must be increased to maintain arterial P CO2 at 40 mmHg
Respiratory regulation is designed to keep arterial P CO2 at 40 mmHg despite changes to CO2 production
What happens when arterial P CO2 increases
Alveolar PO2 must decrease as total pressure cannot exceed atmospheric pressure
Does doubling alveolar Ventilation lead to a doubling of arterial PO2?
No
Why is the quantitative relationship between alveolar ventilation and arterial PO2 complex
PO2 does not equal 0
Respiratory exchange ratio (R) is not usually 1
What does it mean to say that R does not equal 0
More oxygen is removed than CO2 added
When would R be 1
If we only ate carbs
What is the alveolar gas equation
PA O2= PIO2 - PACO2 [FIO2+(1-FIO2)/ R]
What is PIO2 and FIO2
Partial pressure of inspired oxygen
Fractional concentration of O2 in the inspired air
What is the R value in a normal resting individual
0.82
What are normal alveolar values of PO2 and PCO2 at sea level
~100 and 40mmHg respectively
Why is alveolar PN2 increased
R<1
How does total venous pressure compare to atmospheric pressure
Venous is lower as PO2 decreases more than PCO2 increased
Which 2 physical characteristics of the respiratory components affect effectiveness of alveolar ventilation
Elastic properties of the lung and chest wall
Resistance of the respiratory tree
How does lung volume at any point in deflation compare to volume in inflation
Lung volume at any given pressure during deflation is larger than during inflation
When does lung volume fall to 0 if there is no trans pulmonary pressure
NEVER
What is static compliance
The volume change per unit increase in trans pulmonary pressure when there is no air flow
What is the normal range of trans pulmonary pressure
-2 to -10 cmH2O
How compliant is the lung? Give a value
0.2L/cmH2O
At larger lung volumes the lung is _____ compliant
What kind of curve does this give
Less
Flatter slope of pressure volume curve
Specific compliance=?
Compliance
——————
FRC
What is FRC?
Functional residual capacity
How does the specific compliance compare from mice to elephants ?
It is a similar value for all mammals (0.08/cmH2O)
Is compliance uniform throughout the lung?
No the top is less compliant than the base (regional compliance)
How does regional compliance occur
The downward pull of gravity results in lower pleural pressure (more negative) at the apex than the base
What does regional compliance result in
Higher trans pulmonary pressure at the apex results in alveoli being expanded more than alveoli at the base.
This volume difference places the alveoli in the apex in a less compliant portion of the pressure volume curve relative to the base
The base of the lung undergoes a _____ change in volume for a given pressure change relative to the apex
Greater
Why can the lower lung undergo a great increase in volume
It is at a lower volume
As one takes a breath in from FRC a greater proportion of the tidal volume goes to which lung region
Base
Where does greater alveolar ventilation occur
Prove it
The base of the lung
Use Xe 133 and a radiation camera at different levels of lung
This shows lower zone has higher ventilation/ unit volume than middle and low zone
Why do lower lung zones ventilate more
As the lung approaches residual volume, intrapleural pressure> atmospheric pressure
This compresses the base of the lung
When can ventilation of the lower lung occur
Only once intrapleural pressure falls below atmospheric pressure
The apex ventilates well whenver
What is the compliance like in a distensible lung
Abnormally high
Give the consequences of reduced lung compliance
Stuff lung -> more working for same level of ventilation -> cost of breathing increases
Name some causes on reduces lung compliance
Fibrosis
Scarring of alveoli such as when respiratory system is overloaded with pollutants
Name 4 pollutants, what they cause and whose lungs are most frequently affected
Carbon particles: “black lung” in miners
Silica particles: “silicosis” in glass workers
Asbestos particles: “asbestosis” in boiler workers
Cellulose particles: “brown lung” in textile workers
What happens in emphysema?
Increased lung compliance due to alveolar damage leading to a flabby lung
There is no problem inflating the lung but they have great trouble exhaling.
This is caused by a loss of elastic recoil
When are the opposing chest wall and lung pressure equal
At FRC
How to work out trans mural pressure of the lung and chest wall together
Add their individual values
How does reduced compliance affect FRC?
FRC is reduced
What dictates chest walls compliance
Rigidity and shape
Also depends on diaphragm and abdominal structures
How does obesity affect chest wall compliance
Compliance can be decreased if chest wall is deformed
Other than obesity what else may decrease chest walk compliance
Elevation of diaphragm (eg tumour)
Spasticity or rigidity of musculature
How does surface tension occur
Arises at air-liquid interfaces
Attractive forces between water molecules are stronger than those between molecules and the air
The surface therefore because as small as possible
Give LaPlace’s Law
Pressure=4x surface tension/ r
What is LaPlace’s Law applied to alveoli?
Why is it different?
P= 2x surface tension/ radius
The alveolus has only 1 air-liquid interface
Who first appreciated the importance of lung surface tension
Von Neergaard in the late 1920s
Describe Von Neergaard’s experiments
What were the conclusions (2)?
Cat lung was inflated and deflated using air then deflated with saline
1) Saline inflation gives a steeper pressure volume relationship. (Without the air-water interface, the lungs are more compliant)
2) There is greater hysteresis between air filling and emptying curves than for saline filled lungs
How much does surface tension account for in lung elastic recoil
2/3 to 3/4
What did scientists testing noxious fumes find
What discovery resulted
Edema foam coming from the lungs had very stable air bubbles due to reduced surface tension
Pulmonary surfactant
What is pulmonary surfactant
Secreted by cells lining the alveoli (particularly alveolar type 2 cells) that lowers surface tension
It is a rich phospolipid
How does pulmonary surfactant reduce surface tension
How is it made
DPPC
Dependant upon availability of precursors (ie glucose, palmitate and choline) supplied by pulmonary circulation
How is the effect of surfactant on surface tension studied
With a surface balance/ Langmuir trough
A v stable tray containing saline
The area of the surface is expanded and compressed simulating inflation and deflation
Saline, detergent and lung washings are added separately and results of relative area(y) vs surface tension(x) are compared
What are the effects of adding saline, detergent and lung washings to a Langmuir trough
Pure saline: surface tension of 70dynes/cm, irrespective of surface area
Detergent: reduces surface tension, independent of surface area
Lung washings: reduces surface tension but dependent on area with a marked hysteresis. At very low area surface tension falls to vvv low values
What is the role of surfactant
To reduce surface tension in alveoli to increase compliance
Allows alveoli of different sizes to coexist
What would happen to differently sized alveoli without surfactant
LaPlace’s Rule means there would be greater pressure in the smaller alveoli, forcing air into the larger. Therefore at low lung volumes small alveoli would collapse (this process is called atelectasis)
Surfactant stabilises the small alveoli by reducing surface tension in smaller alveoli
How does surfactant decrease surface tension
Molecules of DPPC are hydrophobic at one end and hydrophilic at the other
When aligned on the inner alveoli surface the IMF oppose the attractive forces between surface water molecules
What is the reduction of surface tension dependant on
When is it greatest
The amount of surfactant per unit area
When the film is compressed
When is the reduction in surface tension greatest and why is this?
When the film of surfactant is compressed because at small surface areas the DPPC Molecules are crowded close together resulting in greater repulsion and thus the opposition of surface tension is increased
What happens to DPPC at low lung volumes
What happens when the lungs expand
DPPC molecules are compressed and some molecules are pushed out of alignment, off the surface layer
Alveoli inflate so amount of DPPC per unit area will be less, resulting in a decreased ability to resist surface tension. New surfactant is required to form a new film.
This redistribution of the film may account for hysteresis
Why might patients who have undergone thoracic or abdominal surgery find it hard to breathe deeply
Alveoli expand more than usual in a deep breath so more surfactant is required
These patients may have poor surfactant spreading, which leads to atelectasis due to increased surface tension
When is the foetal lung triggered to fully mature
85-90% of the gestation period
Why is the lung functionally immature before 85% of gestation period
It does not have adequate surfactant production
Which respiratory disease is a common cause of death in premature babies?
Describe
Infant Respiratory Distress Syndrome (IRDS)
JFK lost a child to IRDS
Laboured breathing due to increased surface tension and the decreased compliance
Children would “magically” get better after ~18 days. This is because Type 2 lung cells are late to develop even after birth
How is Hylem Membrane Disease/ IRDS treated
Ventilatory delivery is kept at a positive pressure head so that the pressure is always above atmospheric, keeping the alveoli open, until development of Type 2 cells
This change increased survival rate from 20% to 80%
What do some physiologists believe is the most important role of surfactant
Keeping the alveoli dry
How does surfactant keep alveoli dry
The inward contracting force that collapses alveoli also lowers interstitial pressure ( making it more negative)
This pulls fluid in from the capillaries
Surfactant reduces this by lowering the surface tension
Where does turbulent air flow occur
In large airways such as the trachea and large bronchi at high flow rates (eg during exercise)
Where does laminar flow in the respiratory tree occur
Small airways where flow is slow
What kind of airflow is most prominent in the bronchial tree
Transitional
Give the equation that defines laminar flow
Flow= ΔP/ resistance
What did Poiseuille say resistance =?
8nl/πr^4
n= viscosity L= tube length r= tube radius
What is more important for resistance of a fluid: viscosity or density
Viscosity
Why would you assume that the small airways would provide the most resistance
Where in fact is the site of real resistance
Small radius: if you decrease the radius by a half, the resistance increases 16 fold
Medium sized bronchi
Why do the v small airways not account for the largest reduction in resistance
There are many small airways in parallel. Individual resistance is high but the large number increases cross sectional surface area
What is the equation for resistance in parallel
1/R total = 1/R1 +1/R2 +…+1/Rn
What is the problem with small airways only accounting for a small % of total resistance
Diseases often start in the small airways but go undetected for a long time before the increased airway resistance is detected
What suspends small airways
Parenchyma which acts as guy wires
Discuss autonomic control of bronchial smooth muscle
Parasympathetic stimulates of cholinergic fibres causes bronchial constriction and stimulation of mucus secretion
Sympathetic stimulation of adrenergic fibres results in dilation and inhibition of glandular secretions
What drugs can cause bronchial dilation
When are they often used
Isoproterenol and adrenaline cause dilation by stimulation of the β2 adrenergic receptors in the airways
To treat asthma attacks and marked bronchial constrictions induces by environmental insults eg smoke and dust particulates
How do PCO2 levels affect airway constriction
Increased PCO2 in conducting airways induces dilation while decreased PCO2 induces airway constriction
Why is helium used in underwater breathing simulations
Helium reduces the resistance of breathing
What does the fact that both density and viscosity affect airflow suggest about airflow
Airflow is not simply laminar
Describe a flow vs volume graph for forced expiration
What is on the X axis
Flow increases to a peak but most of the flow is an effort independent decrease
Volume (from TLC to RV)
What is EPP (respiratory)
Equal pressure point
The point in the airway during forced expiration where trans airway pressure is 0
Why can’t peak flow rate be increased
Increased effort increases intrapleural pressure as well as alveolar pressure so trans airway pressure remains constant
What are maximum flow rates primarily determined by and why?
The lungs’ elastic recoil
This is what generates alveolar pressure and therefore the alveolar-intrapleural pressure
How does maximum flow rate change as lung volume decreases
What is the main reason for this
Decreases
Due to the decrease in elastic recoil
How do healthy lungs “push” the EPP up the lung
What happens in emphysema
Because of elastic recoil, the normal lung has added pressure that overcomes intrapleural pressure so EPP is pushed up airway to where the airways won’t collapse due to cartilaginous rings
Less elastic recoil therefore less added alveolar pressure and EPP is moved lower and airways can collapse
What causes wheezing in patients with emphysema
Smaller airways collapse due to lowered EPP so there is no airflow here
Airway pressure in collapsed segments rises to equal alveolar pressure and airway reopens
EPP is set by lung compliance
What is FVC and how is it measured
Forced vital capacity
Measured by forced maximal exhalation
What is FEV1 and how is it normalised
Forced expiratory volume of air in one second
Normalised for lung size by expressing it as a fraction of FVC (FEV1/FVC)
What is FEV1/FVC in normal conditions
0.8
What is FEF25-75%
Forced expiratory flow rate over the middle 50% of the FVC
What is net diffusion dependant on
Surface area
Diffusion pathway
Diffusion gradient for both O2 and CO2
Diffusion coefficient
Give Henry’s Law
Why is this useful
Concentration = partial pressure x solubility
It is more useful to talk about partial pressure of respiratory gases than concentration
Give Fick’s equation using partial pressure and solubility
Net flux=
ΔP x s x area/thickness x D
What is D
Diffusion coefficient of gas
What is d
The diffusion constant for a specific constant In a specific medium
d is proportional to solubility/ square root of Mr
Is a smaller molecule faster or slower to diffuse
Faster
Give solubility constant for CO2 and O2
Give the units
O2: 0.03
CO2: 0.7
(C)O2/ litre plasma/ mmHg
How much more soluble is CO2 than O2 in plasma?
23x
How much faster does CO2 diffuse
20x faster than O2
What is the transit time from the beginning to the end of the pulmonary capillary
<1s
What is a diffusion reserve
When gas equilibration is accomplished with room to spare
What is adequate equilibration of respiratory gases at the alveoli dependant on
Appropriate matching of alveolar ventilation with alveolar blood perfusion
How much O2 is dissolved in arterial blood at 100mmHg
Give cardiac output in heavy exercise
Therefore what is O2 delivery to the periphery
3ml/O2 litre
30L/min
3x30=90ml/min
2 ways that O2 is transported around the body
Dissolved
Bound to Haemoglobin
How many polypeptide chains in a molecule of Hb
4
2 α and 2 β
What happens to Hb type F after birth
This is foetal Hb so is replaced by Hb type A (for adult)
What is Hb Type S
Discuss its structure and how this affects its functioning
Sickle cell haemoglobin
It has a small amino acid substitution in β chain, reducing oxygen affinity and alters the Hb solubility in deoxy form. This results in crystallisation and fragile, sickle shaped RB cells
Briefly describe the oxygen binding structure of a Hb molecule
Each chain has a hydrophobic pocket containing a Fe2+ porphyrin moiety
The 4 subunits bind sequentially to O2 and each reaction improves the affinity of the remaining subunits
Name 4 things that also affect Hb’s affinity for O2
H+,
CO2,
Diphosphoglycerate
Temperature
What is the [dissolved oxygen] proportional to?
The solubility coefficient and the PO2
You have 2 sealed containers separated by a semi Permeable membrane containing 2 solutions with different PO2 levels. What will happen?
What happens if haemoglobin is added to one side (and cannot pass through membrane)?
They will equilibrate with equal PO2 on both sides
The PO2 of the Hb side will drop as dissolved O2 binds to the Hb. Only dissolved O2 counts towards PO2 so the O2 from the other side will diffuse across to equilibrate PO2. The PO2 will be equal but the side with Hb will have more O2 total
How much O2 can 1g of Hb carry
1.39ml
How much Hb does blood have per 100ml
5g of Hb/100
What is the oxygen capacity of blood given 1g of Hb can carry 1.39 ml of O2 and normal blood has 15g of Hb per 100ml
20.8 ml of O2 per 100ml of blood
What is the O2 saturation of Hb at arterial PO2 of 100mmHg
What about mixed venous blood with a PO2 of 40mmHg
97.5%
75%
Discuss the loading plateau of Hb
Hb is largely saturated at all PO2>60mmHg
Therefore quantity of O2 carried by the blood is not much affected by PO2 until it drops below 60mmHg
The quantity of O2 in arterial blood remains the same over large variations in ventilation rate
What does the loading plateau mean for barometric pressure
Fluctuations in barometric pressure have little effect on the quantity of O2 carried in the blood
What shifts the pO2 vs Hb Saturation curve to the right
Increased temperature
Decreased pH
Increased PCO2
Increased DPG
ventilation rarely affects total O2 in the blood, what does this mean
Ventilation can be changed to regulate arterial PO2 without affects oxygen supply to tissues
What happens if PO2 drops below 60
Hb saturation falls rapidly
The steepness of the curve means any right shift will result in Hb giving up O2
Describe the RBC environment in exercising muscle
Therefore…
Acidic
Hypercarbic
Warm
An increase in these factors cause O2 to be offloaded more easily
What is the Bohr Effect
The effect of CO2 and H+ (decrease pH) on affinity of Hb for O2
What is 2,3 DPG and how does it affect the dissociation curve
2,3 diphosphoglycerate
Shifts it right
Where are 2,3 DPG levels highest
In RBCs
How do RBCs make 2,3 DPG
Why would it want to do this
Shunt 1,3DPG to 2,3DPG by DPG
Dismutase
2,3DPG has a high affinity for adult Hb so displaces O2 to the tissue
How does foetal and adult Hb compare in relation to 2,3DPG
F type Hb is less sensitive to 2,3 DPG so the dissociation curve is shifted left. This increases the affinity for O2 at low PO2
Why do F type Hb have high affinity for O2
Foetal PO2= 30mmHg which would give a 55% saturation in adults but it is 75% in foetuses
What happens if the blood bank is depleted of 2,3 DPG
Offloading of O2 is impaired
Especially a problem if lots of blood is transfused
What are the 2 important factors to remember regarding the relationship between PO2, O2-Hb, and oxygen content
Arterial pO2 is related to the amount of O2 dissolved in the plasma
Oxygen content/ Hb saturation is what keeps us alive
Give equation for [blood O2]
1.39x[Hb]x %saturation) + (0.003 x PO2)
What are the 4 categories of hypoxia
Hypoxic
Anaemic
Circulatory
Histotoxic
Which hypoxia refers to a reduced O2 carrying capacity of blood
Anaemic hypoxia
What is hypoxic hypoxia
Low arterial PO2 accompanied by inadequate Hb saturation
What is circulatory hypoxia
When too little oxygenated blood is delivered to tissues
What is histotoxic hypoxia
Characterised by normal o2 delivery to tissue but the cells are unable to use the oxygen available
What does cyanide poisoning result in
Histotoxic hypoxia
What is hyperoxia
When an above normal arterial PO2 occurs
What is it called when you have excess CO2 in the blood
Hypercapnia
What is hypocapnia and how does it occur
Below normal arterial PCO2 levels
Hyperventilation
Why is carbon monoxide deadly
CO has an affinity for Hb 240x greater than that of O2 so binds to Hb instead of O2 forming COHb
If there is 0.1% CO in the air, how much of our Hb will bind to CO
How will PO2 be affected
60%
PO2 will not be changed but total O2 will be dramatically reduced
Why is CO dangerous (5)
1) High Hb affinity
2) left shift in o2 dissociation curve making it difficult to unload the little O2 that may still be bound
3) arterial PO2 is normal, impairing any feedback mechanisms
4) no physical signs of hypoxia because blood stays bright red when CO binds to Hb
5) odourless, colourless, non- irritating
What is the first sensor of CO poisoning
The brain (when the individual loses consciousness)
How can CO poisoning be treated
Pure O2 therapy to compete off CO from Hb
3 forms of transporting CO2 in the blood
Dissolved
Bicarbonate
Carbamino compounds
What does concentration =
Partial pressure x solubility
How much of the carries CO2 is dissolved in the blood
5-10%
Which form of CO2 is the largest fraction in blood
As HCO3-
90%
How is HCO3- formed
Hydration of CO2 (by the action of carbonic anhydrase) and the dissociation of carbonic acid
What is the dissociation constant for carbonic acid
What does this mean at physiological level
How fast is the hydration of CO2
6.1
pH =7.4 so many H+ generated
VERY slow
Give the equation of CO2 to HCO3-
CO2+H2O ↔️H2CO3↔️ H+ + HCO3-
How does CO2 form carbamino acids
How is plasma and Hb well suited for this
Proteins can reversibly bind CO2 to their amine groups
Plasma is 7% proteins so provides a large source
The RBC is 30% Hb
What do most carbamino compounds exist as
Why
What is the issue
RNHCOO-
The dissociation constant of RNHCOOH <6
Induces a large pH change unless adequate buffering occurs
Describe the Haldane Effect
The opposite of the Bohr effect
Deoxy-Hb is a weaker acid so at physiological pH it will bind more H+ so CO2↔️HCO3- equation shifts to the right
HCO3- increases and more is carried by the blood
Deoxy Hb also forms more carbamino compounds
Decreased PO2 increases amount of CO2 carried
How do CO2 and O2 move from blood to tissue
Down their respective partial pressure gradient
What are the H+ generated by formation of HCO3- buffered by
Imidazole groups on His amino acid residues of α and β chains of Hb
These residues have a pK of ~7 making them good buffers in the physiological range
How does HCO3- leave the RBC
What must hAppen
Down it’s concentration gradient
Charge movement is balanced by an influx of Cl- and RBCs accumulate Cl- in exchange for HCO3-
What is Hamburger’s phenomenon
Where does it occur
The influx of Cl- to compensate for the charge movement of HCO3- out of the RBC and the subsequent accumulation of Cl- in exchange for HCO3-
Capillary beds
Why is the Cl- shift so fast
High anion permeability of RBC membrane
What do the extra intracellular HCO3- and Cl- do
Increase intracellular osmolarity and osmotic pressure resulting in water influx and cell swelling
What maintains the gradient for CO2 diffusion into the RBC
Continued efflux of HCO3-
Production of carbamino compounds
H+ buffering by Hb
What does an increase in [H+] and PCO2 facilitate in RBCs
And what does this in turn facilitate
The release of O2 via the Bohr effect
Greater proton binding as a result of the Haldane effect
How is the pH resulting from the solution of CO2 in the blood worked out
Henderson Hasselbach Equation
pH= pKa + log(HCO3-)/(CO2)
What is the pH of blood
7.4
Why is the Henderson Hasselbach equation important for blood pH
pH= 6.1 + log(HCO3-)/(0.03PCO2)
Therefore it is the ratio of HCO3- : dissolved pH that determines blood pH
Thus if the ratio remains the same (20), pH will be 7.4
Why is blood a poor buffer system based on physical chemistry
The pK (6.1) is very far from the pH
Despite physical chemistry, why is the blood a good buffer?
The lungs can alter [CO2] by changing alveolar ventilation
It is an open buffer system
How much carbonic acid do the lungs excrete per day
10,000 mEq
What organ primarily controls HCO3- levels
Kidney
How well does full compensation occur
Never in real life
What are the 3 things measured when checking the CO2:HCO3- ratio
What are the 3 categories for classification
PCO2, HCO3-, pH
Acidosis/ alkalosis;
Respiratory/ metabolic;
Acute/ compensated.
How will you know if a blood shift is respiratory or metabolic
change in CO2 = respiratory
Change in HCO3- = metabolic
How can you tell if a change is acute or compensated
If both CO2 and HCO3- levels have changed
What are normal levels for:
a) pH
b) PCO2
c) HCO3-
a) 7.4
b) 40mmHg
c) 26mmol
Classify someone who has pH 7.6,
PCO2: 43mmHg
HCO3-: 34mmol
What has likely happened
Acute metabolic alkalosis
Vomiting
What are the 2 distinct circulations in the lungs
The bronchial and The pulmonary
Give the purpose of the bronchial circulation
Supplies conduction zone and supporting structures
Source of warmth and humidity
How is the pulmonary circulation associated with the respiratory zone
Intimately
Each time the airways branch, the airways also branch
Give the 3 non respiratory functions of the pulmonary circulation
Blood reservoir
Filtration
Metabolism of vasoactive hormones
Discuss the pulmonary circulation’s role as a blood reservoir
Blood volume in pulmonary capillary bed is approximately equal to stroke volume of the right heart
Contains approximately 500ml or 10% of total blood
Equal distribution between arterial and venous
Discuss the filtration function of the circulation
Protects the critical organs from circulating obstruction such as emboli (fat globules, air, blood clots)
Small pulmonary arterial vessels and capillaries trap these emboli and prevent them from entering systemic circulation and blocking coronary, cerebral, or renal blood flow
Endothelial cells release fibrinolytic agents that dissolve blood clots
Pulmonary capillaries can absorb air emboli
What can be a disadvantage of the lung’s filtration function
Emboli Can cause death if they are very numerous and/ or block a large pulmonary vessel thus impairing gas exchange
Discuss the metabolic function of the pulmonary circulation
Involved in selective metabolism of vasoactive agents
Eg Angiotensin I, which is converted to angiotensin II by angiotensin converging enzyme
Angiotensin II is a potent vasoconstrictor
Noradrenaline, bradykinin, serotonin etc are inactivated
Adrenaline, histamine, and vasopressin are unaffected by passage through the pulmonary circulation
Where is angiotensin converting enzyme found and how effective is jt
On the cell surface of pulmonary endothelial cells
Activation is v fast with 80% of angiotensin I is converted to II during a single passage through pulmonary vasculature
What is the pressure that the whole cardiac output travels through the pulmonary circulation
How is this
10mmHg (compared to 80-90mmHg in systemic circulation)
Flow=ΔP/ R
Many vessels to accommodate flow (like a dense capillary bed)
Vessels are dilated so low resistance
What primarily controls the resistance in pulmonary circulation
Local passive control (not really autonomic)
What happens to resistance when pulmonary venous pressure is increased
Resistance decreases
Why does resistance decrease in pulmonary circulation when pressure increases (2)
Capillary recruitment
Capillary distension
Discuss capillary recruitment in pulmonary circulation
When blood flow increase pressure rises and collapsed vessels are opened, lowering overall pressure
Discuss capillary distension in pulmonary circulation
Vessels have high compliance
Therefore the small increase in pressure increases the vessel diameter decreasing resistance
Discuss pulmonary vascular resistance in regional hypoxia
Localised vasoconstriction to divert blood away from hypoxic region so there is only a small change in pulmonary arterial pressure
Discuss pulmonary vascular resistance in general hypoxia
General vasoconstriction
Generalised increase in pulmonary vascular resistance
Increased arterial pressure leads to pulmonary hypertension and oedema
Low PO2 is thought to directly act on smooth muscle cells of the pulmonary vasculature
What is net fluid exchange across the capillary determined by
The hydrostatic and colloid osmotic pressure across the wall
Are their equal amounts of protein in the interstitial fluid all around the body
No
There is more in the lung as pulmonary capillaries are more permeant to proteins than capillaries in the systemic circulation
What drains the interstitial fluid
Why is this important
Lymph
Stops fluid entering alveoli
What ensures interstitial fluid doesn’t enter the capillaries (2)
Interstitial pressure is negative thus pulling water away from the alveoli
Surfactant serves to act as a barrier to fluid movement that attempts to enter the alveoli via capillary action
What happens in the pulmonary circulation if filtration exceeds removal by lymph
What can cause this (5)
Oedema
An increase in capillary pressure due to left heart failure or general hypoxia
Increased capillary permeability due to oxidative damage (eg by ozone toxicity) or endotoxins
Decrease in capillary colloid osmotic pressure
Increased surface tension which increases negative interstitial pressure
Lymph blockage
What can cause a
a) decrease capillary colloid osmotic pressure
b) increase in surface tension
a) Loss of plasma protein in starvation
b) loss/ lack of surfactant as occurs in acute respiratory distress syndrome
What happens during drowning in fresh water
Fresh water inspired
Rapid diffusion of pure water across alveolar membrane into capillaries due to high colloid osmotic pressure in capillary
This leads to RBC lysis due to hypotonicity
The dilution of extracellular Na and the release of K+ from RBCs leads to cardiac fibrillation and death
What leads to death in sea water drowning
Aspiration of salt water with an osmolarity > plasma results in net flow of water out of capillaries into interstitial space
Increases space of capillary from alveoli
RBCs do not lyse but patient dies of asphyxiation
How much of the lung’s weight is blood
~50%
1mmHg = ?cmH2O
1.36
What is the pulmonary arterial pressure in the top of the lungs compared to the middle
11mmHg less
What are the 3 zones that the lungs is divided into to represent the distinct interactions between pulmonary arterial pressure, alveolar pressure, and pulmonary venous pressure
Zone 1 (upper lung) Zone 2 (middle lung) Zone 3 (lower lung)
How do pulmonary arterial pressure, alveolar pressure, and pulmonary venous pressure vary in Zone 1 of the lungs
What does this mean for blood flow in zone 1
Alveolar > arterial > venous
Pulmonary capillaries are collapsed and there is no flow
How do pulmonary arterial pressure, alveolar pressure, and pulmonary venous pressure vary in Zone 2 of the lungs
How does this come about
What does this mean for blood flow
Arterial> alveolar > venous
There is increased hydrostatic influence due to Zone 2’s increased proximity to the heart
The blood flow in this region of the heart is determined by the difference between arterial and alveolar pressure
How do pulmonary arterial pressure, alveolar pressure, and pulmonary venous pressure vary in Zone 3 of the lungs
How is blood flow determined here?
Arterial>venous> alveolar
Using normal arterial-venous pressure difference
When does venous pressure have influenced over blood flow in the lungs
When it exceeds alveolar pressure
Are the conditions in zone 1 of the lungs normal?
No these do not usually occur in healthy people since arterial pressure in the upright lung is normally sufficient to overcome the small alveolar pressures
When may the conditions in zone 1 occur, pathologically or otherwise?
If pulmonary arterial pressure falls (eg in severe haemorrhage) or if alveolar pressure is increased (eg forced ventilation)
What are regional ventilation-perfusion ratios
Comparisons of the alveolar air flow to the flow of blood in different lung regions
What is normal alveolar ventilation
What is normal total pulmonary blood flow
4 litres per minute
5 litres per minute
What is the normal average VA/Q ratio
What’s the units
Normal ventilation perfusion ratio = 0.8
No units as it is a ratio
Where is ventilation best
Why
Where is perfusion best? Why?
At the base of the lung
The effects of gravity on intrapleural pressure and thus the compliance of the lung
At the base of the lung also due to the effect of gravity in pulmonary arterial pressure
How do airflow and blood flow change across the lung
Why
Increase down the lung
Ventilation and perfusion are gravity dependent
Where is blood flow proportional greatest
What about ventilation
Base of lung
Apex of lung
What is the difference between blood flow between the top and bottom of the lungs
5 fold difference
What is the difference between airflow between the top and bottom of the lungs
2 fold difference
How does VA/Q ratios change from the base to the apex of the lung
0.7 at the base and 3 at the top
However the VA/Q ratio does not change much over the lower 2/3 of the lung
How does the VA/Q ratio change in the bottom 2/3 of the lung?
What about in the top
the VA/Q ratio does not change much over the lower 2/3 of the lung
Over The upper 1/3 of the lung the ratio increases dramatically as a result of the fall in blood flow
Why are VA/Q ratios useful
Mismatches between ventilation and perfusion have marked effects upon alveolar gas exchange
Where does tuberculosis occur typically
Why here?
The apex of the lung
The high VA/Q ratio which is a result of over ventilation relative to blood flow provides a high PO2 environment which is favourable for the mycobacterium tuberculosis
How does the body compensate for a low VA/Q ratio
Increase overall ventilation - this is an acute response as this will result in over ventilation in normal lung units, leading to a deficiency in PCO2 in the alveoli and venous blood
Regional vasoconstriction induces by localised hypoxia will shunt blood away from poorly ventilated alveoli
How does the body compensate for high VA/Q ratios
Local arterial PCO2 will fall, increasing pH. Increased pH
Causes localised increases in airway resistance, shunting ventilation to alveoli with normal VA/Q ratios
How do venous admixtures affect systemic arterial PO2
Lower PO2 to approximately 95mmHg
What is “wasted blood” in the lungs
Any fraction of blood that does not get fully oxygenated
What is a venous admixture
The mixing of oxygenated blood with non oxygenated blood
What are the 2 main causes of venous admixtures
Shunting
Low VA/Q
What are the 2 kinds of shunt that cause venous admixtures
Right to left anatomic shunt
Alveolar shunt
What is a right to left anatomic shunt
Blood passes through an anatomic channel that does not pass the alveoli
There might be a septal defect or the fact that a portion of the venous drainage of the bronchial circulation is dumped into the pulmonary vein, which enters the left heart to be pumped round the body
Are right to left shunts normal?
All individuals have some degree of right to left anatomic shunt
How much of cardiac output is venous admixture in a normal person
1-2% due to bronchial circulation drainage into the pulmonary vein
What is alveolar shunting
When a portion of cardiac output goes past alveoli without coming into contact with alveolar air
Why might an alveolar shunt occur
Pneumonia
Pulmonary oedema
Atelectasis
Other than shunting, how may a venous admixture occur
Low VA/Q ratio - the normal regional distribution of VA/Q ratios contributes to venous admixture
In the normal lung how much of the venous admixture is due to shunting and how much is low VA/Q ratios
20% = shunting
80% is a result of low VA/Q ratios at the base of the lung
What is the name for quiet automatic breathing
What is the most important respiratory muscle here?
Eupnea
The diaphragm
What is the excitatory activity like in the diaphragm when we inhale
What is this activity responsible for
Dramatic and linear
Responsible for the increases Negative intrapleural pressure leading to the reduction in alveolar pressure, causing lung expansion
Describe the electrical activity of the diaphragm during breathing
Linear increase during inspiration
Inspiration is marked by an abrupt cessation of electrical activity which is followed by passive expiration due to the elastic recoil of the lungs
Which instrument was surprisingly vital to our understanding of the role of the brainstem structures in the generation of cyclic breathing
Who did more delicate brainstem transections than this? When?
The guillotine (invented 1789)
Lumsden (1920s)
How is breathing affected after sectioning above the pons
Breathing is unaffected when the vagus (carrying afferent information from the lungs) is intact
How is breathing affected if you cut the vagi after sectioning above the pons
Reduced breathing frequency and increased tidal volume
How is breathing affected if you cut below the medulla
Complete cessation of breathing
How is breathing affected after sectioning above the central medulla
How would a vagotomy affect this
Rhythmic but irregular breathing
Slows the irregular pattern
How is breathing affected if you cut at the level of the upper pons (below pneumotaxic and above apneustic centres)
What happens if both vagi are then cut
Slowed respiration and increases tidal volume
Either cessation of breathing at fuckk inspiration (apneusis) or inspiratory spasms interrupted by intermittent expirations (apneustic breathing)
What were the findings of Lumsden’s experiments in the 1920’s
The central pattern generator for breathing is located in the medullary centre
The apneustic centre prolongs inspiration
The pneumotaxic centre inhibits the inspiratory phase
The Vagal afferent input is important in terminating inspiration
What are the 2 key areas of the medullary respiratory centre
Dorsal respiratory group (DRG)
Ventral respiratory group (VRG)
What is the DRG of the medulla associated with
Inspiration
These neurons project to the upper level motor neurone pool inner sting inspiratory muscles
What is the VRG of the medulla associated
Both inspiratory and expiratory neurons and neuronal projections
What is one theory of the control of Central Pattern Generation
What is the evidence
Inspiratory area cells have the property of intrinsic periodic firing, underlying the basic periodicity of breathing
When all afferent stimuli are abolished, the inspiratory cells generate repetitive bursts of APs to the diaphragm and other inspiratory muscles
What is the inspiratory ramp
How is it turned off
The linear increase in electrical activity signalling from the inspiratory brainstem cells to inspiratory muscles
Turned off prematurely by inhibitory impulses from the pneumotaxic centre
What allows modulation of breathing frequency
The pneumotaxic centre inhibiting the inspiratory ramp, shortening inspiration
True or false:
The VRG and DRG are bilaterally paired and synchronised by cross communication
True
This results in the symmetry of respiratory movement
What part of the pneumotaxic centre inhibits inspiration
The pontine respiratory group (PRG)
What does the PRG in the pneumotaxic centre do
What is the experimental evidence for this
Switches off inspiration, regulating tidal volume and breathing frequency
Direct electrical stimulation of the pneumotaxic centre attenuates the inspiratory ramp
What may play a role in fine tuning the period of the respiratory rhythm
The PRG
Can a normal rhythm exist without the PRG
Yes
What does the apneustic centre do
Evidence?
Prolongs the inspiratory ramp
An intact apneustic centre results in a regular inspiratory phase of the breathing cycle
How does the apneustic centre prolong the inspiratory ramp
Impulses from the centre have an excitatory effect on the inspiratory area of the medulla, prolonging ramp action potentials
How much voluntary control do we have over breathing?
We have override the automatic control of breathing by holding our breath etc but automatic control will eventually reassert control
There is a careful coordination between voluntary and involuntary for activities such as singing and speaking
The feedback system for breathing is a negative feedback system. True or false?
True
What is the variable under closest control in respiration under normal conditions
Arterial PCO2
Name 6 things (not arterial PCO2) that are measured in the regulation of breathing
Chemical composition of peripheral blood and CSF (1 and 2)
state of lung expansion
Distortion of the king’s connective structure
Presence of irritants
Proprioceptive status of the chest wall
Input from Which sensors are overwhelming modulators of respiration
Sensors interrelated with arterial PCO2 eg [H+]
How is breathing activity related to arterial blood PO2
What about to PCO2 and [H+]
Inversely
Directly related
What is a subject’s respiratory drive
The gradient of the graph of alveolar PCO2 (x) vs pulmonary ventilation (y)
What is an effective stimulus to decrease ventilation rate
A reduction in arterial PCO2
How might we suppress the drive to breathe for a short time
By hyperventilating and thus reducing arterial PCO2
Why might an anaesthetised patient stop breathing briefly
If over ventilated by the anaesthetist
Where is the response to PCO2 Levels dominate
In the CNS
Who showed that there were CNS sites sensitive to PCO2 changes
When
Where
Mitchell
1960s
The ventral surface of the medulla (bilaterally located at the level of cranial nerve roots 8-11; additionally chemosensors have been found caudally in the area of the XII nerve root)
How deep are the sites sensitive to PCO2 in the medulla
Very superficial - 200μm below the surface
What is the area between the cranial and caudal PCO2 chemosensitive for?
It is an intermediate zone - an integrator of the 2 areas
Are the PCO2 areas in the brainstem distinct from the DRG-VRG complex
Yes
They have been physiologically identifier but their exact anatomical identification has not been achieved
How do we know the PCO2 sensitive areas are sensitive to PCO2 and affect breathing
How do we know it is neural
Direct local application of saline that is acidic or in equilibrium with high PCO2 values results in breathing
Application of cold solutions or anaesthetic depress ventilation
What are the chemoreceptors controlling breathing surrounded by
Brain ECF (composed of ECF, CSF, and local metabolites)
Which component of the brain ECF is most important for the CO2 chemoreceptors for respiration
Why
CSF
The area is close to the medulla and therefore close the the CSF
How is CSF separated from the brain
By a layer of permanent ependymal cells
What do the blood brain barrier mechanisms allow
Precise regulation of the chemical composition of CSF and brain ECF, preventing noxious agents from easily coming in contact with neural tissue
Where is CSF found in the brain
Fills the 4 ventricles of the brain and outer surfaces of the brain
How is CSF formed
Formed within the ventricles by highly vascularised tissues / the choroid plexuses
what stops CSF being simply plasma filtrate
It is separated from the cerebral circulation by the blood brain barrier so it is a selective secretion
What are the distinct characteristics of CSF
Low in: protein, HCO3-, K+, Ca2+
High in: Na+ and Cl-
What is the only form of proton buffering in the CSF
HCO3-
How permeable to H+, CO2, and HCO3- is the blood brain barrier
It relatively impermeable to H+ and HCO3-
The cerebral capillary endothelium are permeable to CO2
What are interstitial changes in pH in the brain governed by
The diffusion of CO2 across the barrier and the [HCO3-] in the CSF
What is the usual pH of CSF
7.3
How can we determine whether CO2 chemoreceptors in the brain respond to CO2 directly or the change in pH?
Superfusing the CSF with a high PCO2, which results in a drop in pH, stimulates ventilation
Suffusing the area with a solution of high PCO2 but at a constant pH (by increasing HCO3- equally) has no effect on ventilation
Therefore we can conclude the chemoreceptors are responding to [H+] which rises when CO2 diffuses into the CSF when blood PCO2 is high
How does increased ventilation stimulated by decreased PCO2 stop
Increased ventilation reduced PCO2 in the arterial blood and in the CSF and brain interstitial space
What accompanies increased arterial PCO2 to facilitate CO2 exchange between the arterial blood and the CSF
Cerebral vasodilation
Why is a greater change in pH detected in the CSF than peripheral interstitium
What happens if CSF pH is displaced over a long period of time? Why might this be dangerous?
The protein concentration is much lower in the CSF so it has a weaker ability to buffer
A compensatory increase in CSF HCO3- levels
A person with chronic lung disease (resulting in prolonged elevated PCO2) would have a normal CSF pH, leaving them with low ventilation than is required for their abnormally high arterial PCO2
Other than chronic lung disease, what might cause someone to have a normal CSF pH but high PCO2 resulting in inappropriate ventilation rate
If the individual has been breathing 3% CO2 for a period of days
Are the PCO2 chemoreceptors in the brain sensitive to O2?
No therefore changes in PO2 must be detected at a different site
Where are the carotid bodies
Where are the aortic bodies
At the bifurcation of the common carotid arteries
Above and below the arch of the aorta
What are the chemosensitive cells in the carotid bodies
What do they detect
Type 1 or glomus cells
These may also be in the aortic bodies
Changes in PO2, PCO2, and pH
What happens if the glomus cells are stimulated by an fall in PO2
What other changes would provoke a similar response
Inhibition of K+ channel activity, cell depolarisation, and Ca2+ entry leading to NT release. This results in afferent signalling to the medulla and increased ventilation
Increased PCO2, reduced pH
What is hypercapnia
Increased PCO2
How much of the ventilatory response to hypercapnia can be attributed to the peripheral chemoreceptors
What about the response to hypoxia
20-40%
Peripheral chemoreceptors are solely responsible for this response
What are the most important chemoreceptors in the body for ventilatory response to hypoxia
Carotid bodies
How can we unmask the effect of hypoxia upon ventilation without letting CO2 affect results
By controlling alveolar, and subsequently arterial, PCO2 and then testing the effects of hypoxia - CO2 is added to inspired air to keep it constant in the face of changes in ventilation
What happens to ventilation as PO2 drops below 60mmHg
Ventilation increases
When is the marked increase in ventilation as PO2 drops
Why is this value important
When PO2 drops below 60mmHg
It is ideally mated with the O2 dissociation curve - at 60mmHg, Hb is ~90% saturated with O2 under normal conditions so above 60mmHg increased ventilation would have little effect. However, below 60mmHg, Hb saturation drops rapidly, so increases ventilation is required.
What mediates the response to increased ventilation when PO2 drops below 60mmHg
How do we know
Carotid bodies
Without them, severe hypoxia depresses ventilation as a result of suppression of neural activity in the CNS. The loss of hypoxic ventilatory drive has been shown in patients with bilateral carotid body resection
At what level does increased PCO2 result in increased ventilation
Any level
If PCO2 is increased, at what level of PO2 does ventilation increase
100mmHg
What are the 6 peripheral receptors that have been proposed to contribute to the control of ventilation via neural feedback on respiratory centres
Pulmonary stretch receptors Irritant receptors C Fibre Endings Proprioreceptors Baroreceptors Pain and temperature
What is inspired PO2 on the summit of Everest
What is the issue with this
How do we overcome this
43mmHg BTPS
At a normal ventilation rate, our PA O2 is -3.8mmHg
Increasing ventilation 5 fold (hyperventilating), reducing PCO2 to 8mmHg and increasing the alveolar PO2 to 33mmHg
What is the problem with the hyperventilation response to low PO2
The trigger to hyperventilate (LoS arterial PO2) is opposed by the braking effect of the fall in PCO2 when hyperventilating, detected by the central chemoreceptors
How do we stop the brake reducing hyperventilating
Hyperventilating makes the blood alkaline which reduces central chemoreceptor stimulus to increase hyperventilation. Only when HCO3- Levels are reduced can this braking signal be inhibited - then the sustained arterial hypoxic stimulation will be dominant and ventilation rate will increase further
Other than Central chemoreceptor compensation how does continued increase of alveolar ventilation occur
New experimental evidence suggests Input from peripheral chemoreceptors further increase ventilation in response to sustained exposure to hypoxia
When can oxygen diffusion be rate limiting in respiration
At altitude under conditions of high cardiac output
How can oxygen output be increased at altitude
Polycythemia (increased RBC concentration)
Why is polycythemia useful at altitude
Give an example
Increased Hb means although CO2 and O2 saturation is diminished, O2 content is normal
Locals in Peruvian Andes (4600m): arterial blood PO2 is 45mmHg and Hb saturation is 81% but high RBC count means [Hb]= 19.8g/100ml and arterial [O2] =22.4ml/100ml blood
Compare arterial pO2 in locals of the Peruvian Andes and the normal sea level value
Andes: 22.4ml/100ml of blood
Normal: 20ml/100ml
Why might compensatory mechanisms to maintain arterial O2 content in hypoxia be deleterious
Alveolar Generalised hypoxia can lead to pulmonary vasoconstriction but all alveoli are hypoxic so all vessels construct, leading to pulmonary hypertension and eventually pulmonary oedema
How is 2,3DPG involved in the response to hypoxia
How is this response different to effect of pH, increased PCO2 and increased temperature
Increased production of 2,3DPG shifts oxygen dissociation curve to the right, allowing oxygen to be unloaded more easily at the tissues
However, this is a permanent right shift leading to impairment of oxygen loading at the lungs
2,3DPG permanently shifts oxygen dissociation curve to the right, the other effects are reserved in the lungs
How do scuba divers overcome the pressure of the water on their thorax
The air tank’s regulator’s second stage senses the surrounding pressure and provides air to the diver at a pressure approaching that of the surrounding environment
What happens to gases in the body under hyperbaric conditions
Increased pressure forces the poorly soluble gas into solution in body tissues. This occurs particularly in fat where N2 is high
What happens to N2 under hyperbaric conditions
N2 is high in fat but adipose tissue has poor blood supply and blood can carry v litter N2 anyway
Therefore equilibration of N2 between tissues and the environment is slow, taking hours
What happens to N2 as divers ascend from hyperbaric depths
What if ascension is too fast
N2 is removed from tissues
Decompression is rapid and bubbles of N2 form in the blood
Are bubbles of N2 in the blood dangerous
If they are small they can be removed from the circulation
If they are large, they can be painful, even lethal. The nitrogen emboli accumulate in the joints
What is the ‘Bends’
When nitrogen bubbles accumulate in the joints causing severe pain
It is named after patients bending over in pain
What happens in severe cases of the bends
Large numbers of bubbles can result in neurological disorders and death if they make their way to the brain or heart and occlude cerebral or coronary vessels
How might you treat the bends
How can the risk be reduced
Immediate compression then slow decompression
Use specific diving tables to know the best rate of ascent for a given time at certain depths
Use a helium-oxygen mixture
Why does a He-O2 mixture reduce your chance of getting the bends
He is half as soluble as N2 so less is dissolved in tissues under pressure and it is 1/7 the Mr of N2 so diffuses more rapidly through tissue
Other than to reduce the risk of the bends, why would you use He-O2 mixture when diving
At depths of 160ft, N2 behaves as a narcotic, producing feelings of euphoria which is obviously dangerous
He, among other gases, is used to overcome this side effect
This mixture also reduces resistance to flow that occurs as a result of increased density at depth
Which of the following is the rate limiting step in exercise:
Supplying sufficient oxygen
Removing CO2
Neither
Limitation of performance appears to lie at the level of the muscle and its ability to metabolically produce energy and external work
During grades exercise which muscle units are recruited first
What is ventilation rate like accompanying this
Slow, oxidative muscle units
A near linear increase
What happens after we run out of slow oxidative motor units during graded exercise
Give a positive and negative of this
We are forced to recruit fast glycolytic motor units
These have high energy output but use anaerobic respiration, producing large amounts of lactic acid
How does lactic acid from exercise produce CO2
Acid enters the blood, increasing [H+] so blood HCO3- buffers this, forming CO2 which is then expired
What causes ventilation to increase when anaerobic metabolism begins during exercise
Lactic acid is produced and exceeds the buffering capacity of the blood so H+ accumulates, activating peripheral chemoreceptors, which signal to increase ventilation
What is the point of inflection in the ventilation workload graph
The increase in ventilation when the peripheral chemoreceptors are activated by excess lactic acid
It is the anaerobic threshold (AT)
What is the importance of the anaerobic threshold
Important in endurance activity as it is associated with recruitment of glycolytic motor units and production of metabolic acids
Many training regiments aim to delay the onset of the AT
Formula for trans thoracic pressure
Transmural + trans pulmonary
Why can’t residual volume be measured by spirometry
Spirometry measures volumes you breathe out and You can’t breather that amount out
How would you tell if a pathology is restricting lung inflation?
Give assessments of possible results
FEV1/FVC
Should be 80%
If >90% pathology is restrictive (eg emphysema)
If <70% it’s obstructive (eg fibrosis)
A reduce in just a wall compliance will result in what
A decreased functional residual capacity
Give the features of obstructive lung disease
Eg?
Decreased FEV
Decreased FVC
Increased RV
FEV/FVC=~42%
Asthma, tumour, bronchitis, emphysema
Give the features of restrictive lung disease
Eg?
Decreased FEV
Decreased FVC
Decreased RV
FEV/FVC=0.9
Fibrosis
