1
Q
What type of epithelium is the nasal epithelium?
A
Pseudostratified ciliated columnar epithelium containing numerous mucous and serous glands.
2
Q
What is the normal vital capacity per kilogram?
A
60 mL/kg
3
Q
List some techniques for measuring lung volumes.
A
- Water-sealed spirometer
- Dry spirometer
- Body plethysmograph
- Helium dilution
- Nitrogen washout
4
Q
Describe the helium dilution method for measuring lung volumes.
A
- Helium has a low solubility so is hardly absorbed into the blood.
- Subject breathes in a known concentration of helium in a closed system with a spirometer and wait for it to equilibrate.
- Then measure the expired concentration of helium to determine the total lung volume.
5
Q
What is the normal FRC in most normal subjects?
A
2500 mL
6
Q
How long does the oxygen reservoir last when breathing air vs being preoxygenated?
A
- Oxygen consumption: 250 mL/min
- Breathing air : 375 mL of oxygen = 1.5 mins
- Breathing oxygen : 2250 mL of oxygen = 9 mins
7
Q
Describe the relationship between FRC and pulmonary vascular resistance.
A
- PVR is lowest at FRC.
- At low lung volumes, large pulmonary vessel walls are less supported by traction from surrounding tissues and experience hypoxic vasoconstriction.
- At high lung volumes, capillaries are compressed by hyperexpanded alveoli.
8
Q
Define:
dead space
A
Volume of inspired air that does not take part in gas exchange.
9
Q
What are alveolar time constants?
A
The time it takes for an alveolus to fill or empty with gas. It is determined by the resistance to airflow in the airways and the compliance of the alveoli
10
Q
Describe the graph produced by Fowler’s method.
A
- Anatomical dead space
- Mixed alveolar and dead space gas
- Alveolar air
- Closing capacity
11
Q
Describe Fowler’s method.
A
Subject breathes normally, then takes a vital capacity inspiratory breath of 100% oxygen after normal expiration. Exhaled nitrogen is measured during slow maximal expiration to residual volume.
12
Q
Explain the slight rise in exhaled nitrogen at the end of expiration during Fowler’s method.
A
During normal tidal breathing, upper alveoli are better ventilated. During forced vital breath, more oxygen enters lower airways.
At closing capacity, lower airways collapse, causing exhaled gas to come mainly from upper alveoli, which have a higher nitrogen concentration, leading to a slight increase in expired nitrogen.
13
Q
Derive the Bohr equation for calculating physiological dead space.
A
FACO₂ x VA = FECO₂ x VT
VA = VT – VD
FACO₂(VT – VD) = FECO₂ x VT
(FACO₂ x VT) – (FACO₂ x VD) = FECO₂ x VT
FACO₂ x VT – FECO₂ x VT = FACO₂ x VD
VT(FACO₂ – FECO₂) = FACO₂ x VD
FACO₂ – FECO₂/FACO₂ = VD/VT
Use partial pressures; arterial pCO₂ is a surrogate for alveolar pCO₂.
14
Q
What is the normal lung compliance roughly?
A
200 mL/cm H2O
15
Q
What does hysteresis mean with regards to a pressure-volume graph for the lung?
A
The expiratory limb does not follow the same path as the inspiratory limb.
16
Q
State the equation that describes the law of Laplace.
A
- For Spherical bubble (2 surfaces): P = 4T/r
- For One surface: P = 2T/r
17
Q
Define:
dynamic airway compression
A
Compression of the airways by intrathoracic pressure (occurs on forced expiration).
18
Q
Where are the central chemoreceptors located?
A
On the ventral surface of the medulla, where the glossopharyngeal and vagus nerves originate.
19
Q
Describe the structure and function of the dorsal respiratory group.
A
Located at the floor of the 4th ventricle, where sensory afferents for glossopharyngeal and vagus nerves terminate.
- Predominantly inspiratory neurons (phrenic and intercostal)
- Involved in timing of the respiratory cycle.
20
Q
What four nuclei make up the ventral respiratory group?
A
- Botzinger Complex (expiratory)
- Nucleus Para-ambigualis (inspiratory)
- Nucleus Ambiguus (dilator function of larynx/pharynx/tongue)
- Nucleus Retro-Ambigualis (expiratory)
21
Q
What is the function of the pneumotaxic centre?
A
Acts as an off-switch for inspiration, causing earlier termination of inspiration, which increases respiratory rate (RR) and decreases tidal volume (VT).
Part of the pontine respiratory group involved in fine control of respiratory rhythm.
22
Q
What is the function of the apneustic centre?
A
Prolongs inspiration.
Part of the pontine respiratory group involved in fine control of respiratory rhythm.
23
Q
What do central chemoreceptors respond to?
A
Arterial pCO₂ via changes in hydrogen ion concentration in the CSF.
24
Q
What do peripheral chemoreceptors respond to?
A
- Carotid: pO₂, pCO₂, pH
- Aortic: pO₂, pCO₂
25
Describe how **central chemoreceptors** function.
The BBB is **permeable to CO₂** but not to H⁺ or bicarbonate. CO₂ diffuses into the CSF, where it hydrates to form H⁺ and HCO₃⁻, detected by pH-sensitive enzymes.
26
What types of cells make up the **carotid body**?
* **Type 1 (Chief) Cells**: chemoreceptive cells in contact with afferent nerve endings of the sinus nerve (branch of glossopharyngeal)
* **Type 2 (Sheath) Cells**: supporting cells
27
How does **blood flow** affect the carotid body and aortic arch chemoreceptors?
**Aortic Arch**: lower blood flow leads to higher arterio-venous oxygen difference; responds to oxygen content (e.g., hemoglobin) and arterial oxygen tension.
**Carotid Bodies**: higher blood flow means it primarily responds to dissolved oxygen (pO₂) and is more sensitive to ventilation changes.
28
What is the **Hering-Breuer** reflex?
Inhibition of inspiration due to **large airway distension**. Afferent signals travel via the vagus nerve.
29
What is the **normal partial pressure** of oxygen in the atmosphere, alveolar gas, arterial blood and mixed venous blood?
* **Atmosphere**: 21.2 kPa
* **Alveolus**: 14 kPa
* **Arterial**: 13.3 kPa
* **Mixed Venous**: 5.3 kPa
30
What are the two zones of the **airways**?
**Conducting Zone**
- No alveoli
- Generations 1-16 (trachea to terminal bronchioles)
- Volume: 150 mL
- Bulk flow during inspiration and expiration
- Warming and humidifying inspired air
**Respiratory Zone**
- Has alveoli
- Generations 17-23 (bronchioles to alveoli)
- Volume: 3000 mL
- NO bulk flow, gases move by diffusion
- Function: gas exchange
31
State the **equation** for alveolar minute ventilation.
Alveolar Minute Ventilation = (Tidal Volume – Dead Space) x Respiratory Rate
32
What are the two different types of **dead space**?
* **Anatomical**: upper airways and conducting zone
* **Alveolar**: proportion of minute ventilation that does NOT take part in gas exchange due to entering unperfused or underperfused alveoli
33
What factors determine the **diffusion capacity of oxygen** in the lungs?
* Surface area of the lungs
* Diffusion constant for oxygen
* Thickness of the alveolar and capillary membrane
* Difference between the partial pressure of oxygen in the alveoli and the blood
34
State **Fick's** Law of Diffusion.
Flow of Gas is directly proportional to: (A/T) x D(P1 - P2)
## Footnote
A: surface area
T: thickness of interface
D: diffusion constant for oxygen
P1: partial pressure in alveolus
P2: partial pressure in capillary
35
What is the **rate of oxygen diffusion** across the gas exchange interface at rest?
250 mL/min
36
How long does **gas equilibration** across the exchange interface take?
0.25 seconds.
## Footnote
Red cell transit time through capillaries is 0.75 seconds.
37
Define **shunt** in the respiratory system.
Proportion of circulation entering the **LEFT** heart that has **bypassed** lung oxygenation.
38
What is the normal **physiological shunt**?
Includes **bronchial circulation** and **Thebesian drainage** (venous drainage from heart muscle into the left ventricle).
39
Why are the **bases** of the lungs better ventilated than the **apices**?
The weight of the lungs **compresses** the bases, making intrapleural pressure less negative. This results in **lower resting volume** and greater compliance at the bases.
40
What are the **West zones** in respiratory physiology?
* **Zone 1**: Alveolar pressure > arterial pressure; no flow (does not exist normally).
* **Zone 2**: Arterial > alveolar > venous; flow depends on arterial-alveolar pressure gradient.
* **Zone 3**: Arterial > venous > alveolar; flow determined by arterio-venous gradient.
41
How do **shunt** and **dead space** vary between the apex and base of the lung?
Shunt fraction is **higher** at the **bases**; dead space is **greater** at the **apices**.
42
Why is there a **difference** between alveolar and arterial partial pressures of oxygen?
PO₂ at the apex is about 40 mm Hg higher than at the base due to **V/Q differences**.
Ventilation varies less than perfusion.
**Most blood comes from the bases**, which have lower pO₂ and higher pCO₂, lowering arterial pO₂ and raising pCO₂ compared to alveolar gas.
## Footnote
NOTE: Normal alveolar-arterial oxygen difference is 4 mm Hg.
43
What causes an **increase in A-a oxygen** difference?
* **Low V/Q Ratio**: Ventilation significantly reduced relative to perfusion, causing a drop in PAO₂ and a greater drop in PaO₂; can be partially corrected by increasing FiO₂.
* **High V/Q Ratio**: PAO₂ remains stable, but PaO₂ decreases due to reduced perfusion.
44
State the **shunt equation**.
Qt x CaO₂ = (Qs x CvO₂) + ((Qt - Qs) x CcO₂)
Qs/Qt = (CcO₂ - CaO₂)/(CcO₂ - CvO₂)
## Footnote
Qs = shunt blood flow
Qt = total blood flow (cardiac output)
CcO₂ = end capillary oxygen content (from alveolar gas equation)
CaO₂ = arterial oxygen content (from arterial blood gas)
CvO₂ = mixed venous oxygen content (from pulmonary artery sample)
45
State the **oxygen content equation**.
CaO₂ = (Hb x 1.39 x SaO₂) + (0.003 x PaO₂)
## Footnote
1.34 mL of oxygen is carried per gram of fully saturated hemoglobin.
Hb in grams per 100 mL
PaO₂ in mm Hg.
46
What factors increase **haemoglobin affinity** for oxygen?
* Alkalosis
* Hypothermia
* Decreased 2,3-DPG
47
How does **carbon dioxide** shift the **oxyhaemoglobin dissociation curve** in the lungs compared to the tissues?
* **Lungs**: CO₂ is eliminated, raising pH and shifting the curve left, enhancing oxygen binding to haemoglobin.
* **Tissues**: Metabolism produces CO₂ and H⁺, shifting the curve right, facilitating oxygen release.
48
Describe the action of **2,3-diphosphoglycerate**.
* Produced as a side reaction of glycolysis.
* Binds to beta-globin, reducing haemoglobin's affinity for oxygen.
* Enhances oxygen offloading in anaemia and low oxygen states.
49
What is **Hufner's constant**?
Amount of oxygen (mL) carried by **each gram** of haemoglobin: 1.39 mL/g in vitro, 1.34 mL/g in vivo due to minor haemoglobin variants like HbA2 and HbF.
50
What is the **Bohr effect**?
Refers to the **reduced affinity** of oxygen for haemoglobin when pH is low (and CO₂ is high).
## Footnote
This adaptation helps **offload oxygen** in exercising muscles.
51
How much **oxygen** is carried by 100 mL of 100% saturated blood under normal conditions?
20 mL/100 mL
52
State the **oxygen consumption (VO₂)** equation.
VO₂ = CO x (Arterial O₂ Content – Mixed Venous O₂ Content)
= CO(CaO₂ – CvO₂)
53
What is the **normal VO₂** in a healthy subject?
Normal mixed venous pO₂ is around **5.3 kPa**; at this pO₂, haemoglobin is **75%** saturated.
100% saturated blood contains 20 mL/100 mL of oxygen, so 75% saturation gives 15 mL/100 mL.
Therefore:
VO₂ = 5000 x (20 - 15)/100 = **250 mL/min**.
54
What are the four main types of **tissue hypoxia**?
* Hypoxia Hypoxia
* Anaemic Hypoxia
* Ischaemia/Stagnant Hypoxia
* Histotoxic Hypoxia
55
What is the critical intracellular pO2 requires for **aerobic metabolism** to continue?
0.3 kPa
56
What are the **anoxic thresholds** for the brain?
* **2 mins** anoxia = irreversible cell damage
* **4 mins** anoxia = cell death
57
How does **hypercapnia** affect the **ventilatory response** to hypoxia?
Presence of hypercapnia **enhances the ventilatory response to hypoxia**, increasing ventilation rates.
## Footnote
Ventilation changes little until PaO₂ falls below ~8 kPa (≈60 mmHg), after which it rises steeply due to peripheral chemoreceptor stimulation. Hypercapnia increases the ventilatory response to hypoxia, shifting the curve upward, so ventilation is higher at any given PaO₂ compared with normal PaCO₂.
58
How does **hypoxia** affect the **ventilatory response** to hypercapnia?
Hypoxia **enhances the ventilatory response** to hypercapnia.
## Footnote
Minute ventilation increases with rising PaCO₂, showing an approximately linear response between ~5–10 kPa due to central chemoreceptor stimulation. At very high PaCO₂, respiratory depression may occur. Anaesthetic agents and opioids reduce respiratory centre sensitivity to CO₂, producing a rightward shift of the curve, so higher PaCO₂ is required to achieve the same level of ventilation.
59
What mediates the **vasoconstrictive response** of the pulmonary vasculature to tissue hypoxia?
* Inhibition of nitric oxide production
* Local production of vasoconstrictors (e.g. endothelin)
* Direct effect of hypoxia on vascular smooth muscle
60
Why is end-tidal CO₂ **slightly lower** than PACO₂?
Due to mixing with expired gas from unperfused alveoli (dead space).
61
What are the four main causes of **hypercapnia**?
* Increased inspired pCO₂ (rebreathing)
* Primary respiratory depression (e.g. CNS depression)
* Increased CO₂ production (e.g. sepsis, MH)
* Compensatory (to metabolic alkalosis)
62
What are the **neurological effects** of hypercapnia?
* Increased cerebral blood flow
* Increased ICP (due to vasodilation)
* Narcosis (at pCO₂ > 12 kPa)
* Autonomic effects (due to increased circulating catecholamines)
63
Why is the ventilatory response to **respiratory acidosis** greater than to **metabolic acidosis** of the same severity?
* CO₂ crosses the BBB rapidly, dissolving in CSF to release H⁺, which can't return across the BBB, causing a drop in CSF pH.
* BBB is **more permeable to CO₂** than to H⁺.
64
What are the respiratory effects of **hypercapnia**?
* Linear increase in minute ventilation
* Pulmonary vasoconstriction (if PaCO2 > 7)
* ODC shifts to the right
65
What are the **cardiovascular effects** of hypercapnia?
* Impaired heart rate and contractility (due to acidosis)
* Systemic vasodilation and pulmonary vasoconstriction
* Arrhythmia
* Increased catecholamine release (opposes the direct myocardial impairment mentioned above)
66
State the main **physiological buffers** and their buffering **capacity**.
* Bicarbonate: 18 nmol H+ per L
* Haemoglobin: 8 nmol H+ per L
* Plasma Proteins: 1.7 nmol H+ per L
* Phosphate: 0.3 nmol H+ per L
**TOTAL: 28 nmol H+ per L**
67
What is the solubility coefficient of **carbon dioxide** at 37 degrees?
0.231 mmol/L/kPa
## Footnote
This describes the amount of CO2 dissolved in a solvent for a given partial pressure (i.e. how well does CO2 dissolve in a liquid)
68
Which mineral is **carbonic anhydrase** dependent on?
Zinc
## Footnote
Zinc hydrolyses water to form a reactive Zn–OH species. A nearby histidine removes H⁺ from the zinc-bound water and transfers it to surrounding buffer molecules. Carbon dioxide then combines with Zn–OH to form HCO₃⁻, which subsequently dissociates from the zinc atom.
69
What is **carbamino carriage**?
Amino groups of haemoglobin can combine with CO2 to form **carbamic acid**. Deoxyhaemoglobin is about 3.5 times more effective at carbamino carriage than oxyhaemoglobin.
## Footnote
NOTE: This is a major component of the Haldane effect. Oxygenation reduces its affinity for CO2.
70
# Define:
Haldane effect
Increased capacity of haemoglobin to carry **carbon dioxide (CO2)** in **deoxygenated** blood compared to oxygenated blood.
## Footnote
Essentially, when hemoglobin releases oxygen, it can then pick up more CO2, and conversely, when it binds oxygen, it releases CO2.
71
Which **amino acid** is primarily responsible for the buffering capacity of haemoglobin?
Imidazole group of histidine
## Footnote
Each Hb tetramer has 38 histidine molecules.
72
Why does the **pKa** of a buffer matter?
Buffering capacity is a measure of a solution's ability to **resist changes in pH** when acid or base is added .
## Footnote
A buffer works best when its pKa is close to physiological pH because, under these conditions, the buffer contains substantial amounts of both the weak acid and its conjugate base. This allows it to neutralise added acid or base effectively, thereby minimising changes in pH.
73
What **mechanism** explains the **Haldane effect**?
* In **deoxyhaemoglobin**, the imidazole group of histidine is more basic.
* As O₂ dissociates from haemoglobin, histidine binds more H⁺.
* Removal of H⁺ shifts the carbonic acid equilibrium towards H⁺ and HCO₃⁻ generation, 'consuming' CO₂.
* This increases CO₂ movement into red cells.
* **Deoxyhaemoglobin** also enhances carbamino carriage.
## Footnote
The Haldane effect describes how oxygen binding affects carbon dioxide transport in the blood.
74
What is the **difference** between the Haldane effect and the Bohr effect?
**Haldane effect** is what happens to pH and CO2 binding because of oxygen, while **Bohr effect** is what happens to oxygen binding because of CO2 and lower pH.
75
How are H⁺ and HCO₃⁻ generated by **carbonic anhydrase** in red cells managed?
* **Haemoglobin** buffering: H⁺ is absorbed by histidine residues.
* **Hamburger Shift**: HCO₃⁻ is exchanged for Cl⁻ via Band 3 protein.
## Footnote
NOTE: Hereditary spherocytosis is caused by an inherited defect in Band 3.
76
What is the relationship between **partial pressure of carbon dioxide (PCO₂)** and the **amount of CO₂** carried in the blood?
Higher PCO₂ **increases CO₂** transport in blood.
77
What is the **difference** between dynamic compliance and static compliance?
**Dynamic compliance** is affected by both airway resistance and elastic resistance, while **static compliance** is affected by elastic resistance alone.
78
What is **closing capacity** and how does it change with **age**?
**Closing capacity** (CC = RV + CV) is the lung volume at which **small airways close** during expiration.
With age, **CC increases and may exceed FRC**, causing airway closure during normal tidal breathing.
79
How does **hypothermia** affect blood pH?
As temperature decreases, **CO₂ solubility increases**, requiring more total CO₂ to maintain the same PCO₂.
Lower temperature **reduces** water ionization, increasing pH by about 0.016 per degree drop.
Thus, if CO₂ production and excretion remain constant, hypothermia leads to **alkalosis**.
80
What is the **alpha stat hypothesis** regarding responses to hypothermia?
As temperature decreases, the **ionization state of histidine changes**, affecting its buffering ability. This helps **counteract** the rise in blood/tissue pH.
81
List the mechanisms and possible causes of **respiratory acidosis**.
* **Increased inspired CO2**: rebreathing
* **Increased production of CO2**: hyperthermia, hyperthyroidism, laparoscopic surgery
* **Decreased excretion**: increased dead space, failure of respiratory muscle function
82
What does the **alveolar gas equation** show?
The **partial pressure of oxygen** within the alveolus once the partial pressure of oxygen delivered and the amount consumed to meet the **metabolic demands** of the body have been considered.
83
State the **alveolar gas equation**.
PAO₂ = FiO₂(Patm - Ph₂o) - (PCO₂/RQ)
84
Why is **saturated vapour pressure** important in the alveolar gas equation?
Air becomes **100% saturated** with water in the airways. The SVP of water at body temperature is **6.3 kPa**.
## Footnote
According to Dalton's law, the vapour pressure must be subtracted from the atmospheric pressure.
85
How does **FiO₂** change with altitude?
It doesn't; **FiO₂** remains constant, but total atmospheric pressure decreases, leading to lower **pO₂**.
86
What causes high altitude **pulmonary oedema**?
Caused by excessive **pulmonary vasoconstriction**
87
What are some of the consequences of rapid ascent when scuba diving?
* Barotrauma in air-filled spaces (e.g. lungs, ear)
* Arterial air embolus
* Bubbles forming in vessel-poor tissues (e.g. cartilage) with avascular necrosis
* Potentially permanent neurological damage
88
List some indications for **hyperbaric oxygen therapy**.
* Anaerobic infections
* CO poisoning
* Decompression sickness
89
What are some important considerations when **air transferring** an unwell patient?
* If hypoxic at sea level, the patient is more vulnerable to desaturation and requiring more oxygen at altitude.
* Pressurisation and depressurisation in planes occurs suddenly which can cause air filled spaces (e.g. pneumothorax, bulla) to expand rapidly.
* Boiling point of volatiles falls.
90
Why is the pressure in the **lungs** different from the pressure generated by the **ventilator**?
Energy is lost due to **airway resistance**. At end inspiration and end expiration, the pressure between the lungs and ventilator will **temporarily equilibrate** because there is no air flow meaning that there can be no resistance.
91
# Define:
compliance
Change of **volume** with respect to pressure (a measure of ease of expansion).
C = ΔV/ΔP
92
What is the **relationship** between compliance and elastance?
**Elastance** is the measure of the tendency of a structure to return to its **original shape** after deformation, while **compliance** refers to the ability of a structure to **stretch or deform** under pressure.
## Footnote
In respiratory physiology, high compliance indicates easier expansion of the lungs, while high elastance indicates a stiffer lung that requires more effort to expand.
93
What are some causes of **high lung compliance**?
Factors such as **age** and **emphysema** can lead to increased lung compliance.
## Footnote
High lung compliance indicates that the lungs can expand easily, often associated with conditions that damage lung tissue.
94
Describe the balance between **compliance** and **elastance** in **lung physiology**.
Lungs must be compliant to **expand easily** during inspiration and **elastic** to deflate during expiration without excessive effort from expiratory muscles.
95
What is the **work of one inspiration** in joules?
0.36 J
## Footnote
NOTE: For 15 breaths/min, Power = 0.36 x 15/60 = 0.09 J/s = **90 mW**.
As respiratory muscles are only 10% efficient, power for resting breathing is around **900 mW**. Total metabolic rate at rest is 80-90 W, so respiratory power is about 1% of energy consumed.
96
Why does **hyperventilation** require more power?
Rapid breathing increases flow rates, causing **more turbulence**. Turbulent flow demands **more power** than laminar flow for the same rate, leading to **higher energy consumption** by respiratory muscles. Oxygen demands may exceed supply, causing hypoxia.
97
What is the **partial pressure** at which aerobic metabolism is no longer possible?
Around **0.13 kPa**
## Footnote
This point indicates the threshold for aerobic metabolism to occur effectively.
98
Why might **venous saturations** be increased in cyanide poisoning?
Cells are unable to utilise oxygen despite an adequate supply, this leads to **reduced cellular consumption** and venous oxygen saturations may be elevated.
99
Describe how **carbon dioxide** is carried in **venous** and **arterial** blood.
* **Venous**: 10% dissolved, 60% bicarbonate, 30% carbamino
* **Arterial**: 5% dissolved, 90% bicarbonate, 5% carbamino
100
List some key characteristics of **turbulent flow**.
* Flow is proportional to the **radius squared**.
* Flow is proportional to the square root of the **pressure gradient**.
* Flow is inversely proportional to the **length and density** of the fluid.
101
State Fick's law of diffusion with regards to **renal replacement** therapy.
Area x Concentration Gradient/Thickness
102
What is the **isothermic boundary point**?
The point at which inspired air reaches **37ºC** and a relative humidity of **100%**.
## Footnote
This is normally achieved a few centimeters distal to the carina.
103
What is the **half-life of carboxyhaemoglobin** in air vs when breathing oxygen?
Air: **4-5 hours**
100% Oxygen: **1 hour**
104
State the equation for calculating **pulmonary vascular resistance** that will give the value in dyne.s-1.cm-5.
PVR = 80 x (Mean Pulmonary Artery Pressure – Left Atrial Pressure)/Cardiac output.
## Footnote
NOTE: Multiplying by 80 is the factor required to change from mmHg·min/L to dyne.s-1.cm-5.
105
How do the carotid body and aortic arch chemoreceptors **differ** in their response to oxygen?
* **Carotid bodies** have high flow so get all of their oxygen from dissolved O2 - therefore mainly responds to changes in pO2 (ventilatory).
* **Aortic arch** has lower flow and respond to changes in both oxygen tension and oxygen content.
106
Describe how beta-2 stimulation leads to **bronchodilation**.
1. Stimulation causes increased adenylate cyclase activity
1. Increased cAMP
1. Activation of PKA
1. Activation of myosin light chain phosphatase
1. Smooth muscle relaxation
107
Describe the **oxygen saturation of foetal blood** at different points in their circulatory system.
* Umbilical vein: 80-90%
* Aorta: 65-70%
* Umbilical artery: 40%
108
What is the normal range for **minute volume**?
70-110 mL/kg/min
109
What shifts the **oxy-haemoglobin** dissociation curve to the **left**?
Factors that increase **affinity**:
* Increased pH
* Decreased temperature
* Decreased 2,3-DPG
* Decreased pCO₂
* Methaemoglobinaemia
* Carbon monoxide
110
What shifts the **oxy-haemoglobin** dissociation curve to the **right**?
Factors that decrease **affinity**:
* Reduced pH
* Increased temp
* Increased 2,3-DPG
* Increased pCO2
* Anaemia
* Pregnancy
* Altitude
111
What is the hydrogen ion concentration at a **pH of 7.4**?
40 nmol/L
112
What is the estimated **functional residual capacity** in most healthy subjects?
30 mL/kg
113
List some causes of **increased** ETCO2.
* Hypoventilation
* Rebreathing
* Sepsis
* Malignant hyperthermia
* Hyperthermia
* Hypermetabolism
114
List causes of **reduced** ETCO₂.
* **Equipment**: disconnection, leak, blocked sampling line
* **Ventilation**: hyperventilation, esophageal intubation
* **Perfusion**: hypotension, PE, cardiac arrest
* **Patient**: bronchospasm, hypothermia
115
Outline the phases of **Fowler's method**.
Patient breathes air through **mouth**, then takes a maximal breath of **100% oxygen**.
* **Phase I**: No nitrogen detected. Gas comes from the conducting airways (anatomical dead space).
* **Phase II**: Rapid rise in nitrogen concentration as alveolar gas mixes with dead-space gas.
* **Phase III**: Alveolar plateau where gas originates predominantly from alveoli with relatively constant nitrogen concentration.
116
Outline how the **respiratory quotient** varies with diet.
* **Carbohydrates**: 1
* **Protein**: 0.8-0.9
* **Fat**: 0.7
117
How does Phase 4 of **Fowler's method** relate to **closing capacity**?
Phase 4 shows continued emptying of apical alveoli after basal ones close. These **apical alveoli** initially had more nitrogen due to receiving less of the 100% O₂ breath, causing the rise in nitrogen concentration.
118
State the equation for **oxygen delivery**.
Oxygen delivery (DO₂) = cardiac output x oxygen content
## Footnote
**Cardiac output** (ml/min) = heart rate (beats/min) x stroke volume (ml/beat)
**Oxygen content** = (bound oxygen) + (dissolved oxygen) = (Hb (g/dL) x 1.34 x SpO₂) + (0.0225 x PaO₂)
119
# Define:
base excess
Amount of acid or base needed to return **blood pH to 7.4** at normal PaCO₂ (5.3 kPa or 40 mmHg). Assumes set Hb and plasma protein concentration. Reflects metabolic component of acid–base balance.
120
What is the **difference** between standard and actual base excess?
**Standard base excess** is calculated assuming blood is diluted to mimic the extracellular fluid, with a lower haemoglobin concentration (50 g/L).
This reflects the body's overall buffering capacity.
It is usually higher than **actual base excess**, which reflects buffering in whole blood, because blood has more haemoglobin and better buffering capacity than extracellular fluid.
121
State the formula for **static lung compliance**.
Cstat = Vt/Pplateau-PEEP
122
What is the **resting oxygen consumption** in ml/kg/min in adults and neonates?
* **Adults**: 3.5 mL/kg/min (1 MET)
* **Neonate**: 7 mL/kg/min
123
What is the **dead space** to tidal volume ratio in healthy individuals?
0.3 irrespective of age
124
Why does **methaemoglobinaemia** impair oxygen delivery?
Methaemoglobin has iron in the **ferric state** (Fe³⁺), which can't bind oxygen. This increases the affinity of remaining Fe²⁺ for oxygen.
125
What is **1 MET**?
3.5 mL/kg/min oxygen consumption
126
What is the **normal A-a difference** in healthy adults breathing air?
< 2 kPa (15 mm Hg)
127
How does the **oxygen dissociation curve** of myoglobin compare to that of hemoglobin?
Myoglobin exhibits a **rectangular hyperbola** shape in its oxygen dissociation curve and has a very high affinity for oxygen.
## Footnote
This high affinity allows myoglobin to effectively store oxygen in muscle tissues.
128
What is the **respiratory quotient (RQ)**?
Ratio of CO₂ produced to O₂ consumed per unit time.
RQ = CO₂ produced / O₂ consumed
129
Why is the **descending** component of the **flow volume graph** remarkably similar despite varying the way in which expiration is achieved?
**Dynamic compression** limits expiratory flow and the flow rate is independent of effort.
## Footnote
I.e. during forced expiration, intrapleural pressure exceeds intraluminal pressure causing them to be compressed and limiting flow (at the equal pressure point, small airways collapse)
130
State the equation for **total compliance** of the lung and chest wall.
1/Ctotal = 1/Clung + 1/Cchest wall
131
How does **pulmonary vascular resistance** change with lung volume?
Pulmonary vascular resistance (PVR) varies with **lung volume**: it is lowest at functional residual capacity (FRC). **Above FRC**, extra-alveolar vessels are distended, **reducing resistance**, while alveolar vessels are stretched, increasing resistance. **Below FRC**, smaller alveoli reduce stretch on capillaries but overall **PVR increases due to compression** of extra-alveolar vessels.
## Footnote
Understanding these changes is crucial for assessing lung function and hemodynamics.
132
What is a **Davenport diagram**?
A graphical representation of the **Henderson-Hasselbalch equation**, illustrating the relationship between **pH**, **pCO2**, and **HCO3-**.
## Footnote
This diagram is used in physiology to understand acid-base balance in the body.
133
A decrease in which **blood test parameter** can make the interpretation of base excess and anion gap difficult?
Hypoalbuminaemia
| (albumin is a prominent anion)
134
What is the main contributor to an increase in **minute ventilation** in pregnancy?
Increase in tidal volume
135
Which part of the airways has the **greatest airway resistance**?
Medium-sized bronchi
## Footnote
NOTE: You have to consider both diameter and cross-sectional area (terminal bronchioles have a small diameter but large cross-sectional area).
136
What can stimulate a rise in **2,3-DPG**?
* Chronic hypoxia (e.g. altitude)
* Anaemia
* Exercise (intense or prolonged)
137
What is the **difference** between standard and plasma bicarbonate?
* **Plasma**: directly measured from blood and reflects current metabolic/respiratory status, affected by both metabolic and respiratory.
* **Standard**: calculated value based on theoretical average pCO2 of 5.3 kPa and normal Hb. Reflects the pure metabolic contribution.
138
What effect do **metabolic** and **respiratory acidosis** have on **hypoxic pulmonary vasoconstriction**?
* **Metabolic**: reduces HPV, causing vasodilation (helps eliminate CO₂).
* **Respiratory**: increases HPV, as high pCO₂ indicates poor ventilation, diverting blood to better-ventilated areas.
139
# Define:
elastance
A structure's tendency to **return to its original shape** after deformation.
## Footnote
It is the reciprocal of compliance.
140
What does a **volume-time graph** illustrate in relation to **obstructive and restrictive** lung disease?
A volume-time graph shows the differences in **airflow patterns** during breathing in obstructive and restrictive lung diseases.
## Footnote
Obstructive diseases typically show a prolonged expiration phase, while restrictive diseases show reduced lung volumes.
141
List some key **differences** between the **respiratory system** of a child vs an adult.
**Narrowest point of airway**
* Child: cricoid cartilage
* Adult: true vocal cords
**Minute ventilation**
* Child: higher (100–150 mL/kg/min)
* Adult: ~60 mL/kg/min
**Basal oxygen consumption**
* Child: higher (~6 mL/kg/min)
* Adult: ~3.5 mL/kg/min
**Epiglottis**
* Child: larger and more floppy
* Adult: smaller and more rigid
142
List factors that reduce transfer factor on **lung function testing**.
* Emphysema
* Primary pulmonary hypertension
* Pulmonary embolism
* Pulmonary fibrosis
143
What is a **delta ratio** with regards to blood gas analysis?
It is a ratio of the **change in anion gap** to the change in bicarbonate concentration
**< 0.4**: NAGMA (i.e. not much change in anion gap, but big change in bicarbonate)
**1-2**: HAGMA (i.e. similar changes in both anion gap and bicarbonate)
**0.4-0.8**: combination of normal and high anion gap metabolic acidosis
144
Why is **carbon monoxide** used to measure diffusion capacity?
Uptake is **limited by diffusion**, not blood flow. **CO is absent** in venous blood under normal conditions and has a higher affinity for Hb, making its partial pressure essentially **zero** in pulmonary capillaries.
145
What effect does **anaemia** have on the oxygen dissociation curve?
Shifts to the **right** to facilitate offloading (via the production of 2,3-DPG).
146
Why does carboxyhaemoglobin cause a **hyperbolic dissociation curve**?
CO binds directly to haemoglobin’s heme sites, leaving **fewer available** for O₂, and **increases the affinity** of the remaining sites. This disrupts cooperative interactions between subunits, so **O₂ binds more like a monomeric, non-cooperative protein**, producing a hyperbolic curve.
147
What is **myoglobin** and why is its dissociation curve **hyperbolic**?
**Muscle protein** that binds and stores oxygen, facilitating diffusion during high metabolic demand.
Monomeric structure means it **cannot demonstrate cooperative binding**, resulting in a hyperbolic dissociation curve.
148
What is the **pKa** of **histidine residues** on haemoglobin?
6.8
149
List some factors that **increase** FRC.
* Asthma
* Emphysema
* PEEP
* Age
150
List some factors that **decrease** FRC.
* Lying flat
* Obesity
* Pulmonary oedema/fibrosis
* Pregnancy
* Increased abdominal pressure/distension
151
What is the pKa of the **carbonic acid-bicarbonate** buffer system?
6.1
152
What is the pKa of the **phosphate buffer** system?
6.8
153
What are the arterial, venous, and P50 pO₂ levels in a **normal oxyhemoglobin dissociation curve**?
* **Arterial pO₂**: 13.3 kPa, 97% saturation
* **Venous pO₂**: 5.3 kPa, 75%
* **P50**: 3.5 kPa (50% saturation)
## Footnote
P50 is used to compare affinity.
154
What is the **double Bohr effect**?
Increase in pO₂ in maternal intervillous sinuses aids **oxygen unloading**. Decrease in pCO₂ in fetal circulation aids **oxygen loading**. Thus, the ODCs for maternal and fetal circulation **shift in opposite directions**.
155
# Define:
hypoxia
**Inadequate** oxygen supply or **inability** to utilise oxygen at the cellular level.
156
What are the four types of **hypoxia**?
* **Hypoxic**: arterial pO₂ < 12 kPa (causes: diffusion impairment, hypoventilation, V/Q mismatch, shunt)
* **Anaemic**: inadequate oxygen-carrying capacity (e.g., CO poisoning)
* **Stagnant**: reduced tissue perfusion (e.g., shock)
* **Histotoxic**: inability of tissues to use oxygen (e.g., cyanide poisoning)
157
What happens to venous pO₂ in **anaemic hypoxia**?
It decreases (to about 3.5 kPa). An **increase in oxygen extraction** occurs to compensate for reduced oxygen delivery.
158
What happens to venous pO₂ in **cyanide poisoning**?
The pO₂ **increases** (as does venous saturation), this occurs because cells can't use oxygen.
159
What does the **oxygen cascade** illustrate?
Illustrates **oxygen transport** from the **atmosphere to body tissues**, showing changes in **partial pressures** at each stage.
## Footnote
This concept is crucial for understanding how oxygen is delivered to tissues and the factors that can affect this process.
160
What are the three main causes of an **increased A-a gradient**?
* Diffusion impairment (e.g. pulmonary oedema)
* V/Q mismatch (e.g. COPD)
* Shunt (e.g. pneumonia)
## Footnote
NOTE: normally < 2 kPa
161
Why is there no **alveolar-arterial pCO₂ gradient**?
High diffusibility of CO₂ allows **rapid equilibration** across the alveolar membrane.
## Footnote
This stability occurs even with ventilation-perfusion mismatch due to CO₂'s sensitivity to changes in alveolar ventilation.
162
Why does increasing **minute ventilation** affect **pCO₂** but not **pO₂**?
**CO₂** diffuses rapidly; alveolar concentration depends on production and ventilation.
**pO₂** is less affected by ventilation changes since oxygen is mainly carried bound to hemoglobin (usually fully saturated), and alveolar pO₂ is buffered by high blood oxygen content.
## Footnote
Hyperventilating still delivers the same **FiO₂**.
163
How does water vapor pressure in the airways remain constant at **6.3 kPa** regardless of altitude?
Because the **saturated vapor pressure** (SVP) of water depends on **temperature**, not ambient pressure.
164
How does **minute ventilation** affect the levels of **pO₂ and pCO₂** in the body?
Increasing minute ventilation **lowers pCO₂** levels while having a lesser effect on pO₂ levels.
## Footnote
This occurs because **CO₂** is more sensitive to changes in ventilation compared to oxygen, which is primarily carried by hemoglobin.
165
How do **ventilation and perfusion** change across the lung?
Ventilation and perfusion vary due to **gravitational effects**, with greater ventilation and perfusion at the base of the lung compared to the apex.
## Footnote
This gradient affects gas exchange efficiency in different lung regions.
166
How does **ventilation** vary from the apex to the base of the lung?
**Intrapleural pressure** increases from apex to base (0.2 cm H₂O/cm vertical displacement).
Apex: -8 cm H₂O
Base: -1.5 cm H₂O
This means alveoli at the apex are larger; thus, **base alveoli are more compliant** and fill more for a given change in intrapleural pressure (i.e., basal alveoli are better ventilated).
167
How does **positive pressure ventilation** alter the **West zones**?
Increases alveolar pressure, potentially shifting lung areas into zone 1.
This effect worsens with hypotension.
168
How does ventilation across the lung differ in an **anaesthetised** patient compared to an upright **awake** patient?
* **Increased apical ventilation** in anaesthetised patients.
* This occurs due to decreased **FRC** from loss of muscle tone and cephalad diaphragm displacement.
* Upper alveoli are on a more compliant part of the pressure-volume curve.
* This effect is counteracted with **PEEP**.
169
What is **shunt** and what are its causes?
Blood entering the arterial system **without passing** through ventilated lung areas.
**Intrapulmonary**: bronchial veins, thebesian vessels (physiological), lung collapse.
**Extrapulmonary**: cyanotic heart disease.
170
Why is it important for the subject to breathe **100% oxygen** when calculating **shunt fraction**?
* It removes the impact of V/Q **mismatch** on PaO₂.
* At high FiO₂, poorly ventilated alveoli can reach maximum O₂ saturation, eliminating their contribution to **hypoxemia**.
* Thus, only blood that **bypasses alveoli** (i.e., shunt) remains desaturated.
171
What does the **iso-shunt diagram** illustrates?
The extent to which **increasing FiO₂ affects PaO₂** declines as the shunt fraction increases.
172
List changes that can **increase anatomical dead space**.
* Sitting up
* Neck extension
* Increasing age
* Increasing lung volume
173
List some changes that **decrease anatomical dead space**.
* Intubation
* Tracheostomy
* Hypoventilation
* General anaesthesia
174
Describe how **anatomical dead space** is measured.
**Fowler's method**: single-breath nitrogen washout using rapid nitrogen gas analyser, nose clip attached, subject breathes in and out via mouthpiece. From end of normal expiratory breath, subject takes maximal breath of **100% oxygen to vital capacity**. They then exhale at slow, constant rate while **rapid nitrogen analyser** records nitrogen concentration against volume.
175
What is the **Bohr equation**.
This refers to **physiological dead space** (anatomical + alveolar).
## Footnote
Normal dead space is around 35%.
176
List some factors that **increase alveolar ventilation**.
* Pulmonary embolus
* General anaesthesia (apparatus dead space and reduced VT)
* Positive pressure ventilation (preferentially ventilates non-dependent alveoli)
177
What lung volumes can be measured with a **spirometer**?
* Vital capacity
* Inspiratory and expiratory reserve volume
* Tidal volume
178
List average values for a healthy 70-kg man for the following parameters:
* Total lung capacity
* Vital capacity
* Tidal volume
* Inspiratory reserve volume
* Expiratory reserve volume
* Residual volume
* Functional residual capacity
* **TLC**: 6000 mL
* **VC**: 4800 mL
* **TV**: 400–600 mL
* **IRV**: 2500 mL
* **ERV**: 1200 mL
* **RV**: 1200–1500 mL
* **FRC**: ~3000 mL (upright) → ~2000–2500 mL (supine)
179
Describe the **nitrogen washout method** for measuring **RV** and **FRC**.
* Subject rebreathes from a bag with a **known volume of nitrogen-free gas**. Process starts from maximum expiration (for RV) or end of a tidal breath (for FRC).
* Amount of nitrogen at the start comes from the subject's lungs and distributes across the lung and bag.
* As the bag volume and nitrogen concentration are known, the equilibrium concentration in the bag can be measured to calculate FRC or RV.
## Footnote
NOTE: This is the same principle as the helium dilution method, except N₂ is already in the lungs (partial pressure is determined by the fractional concentration of N₂ in the air).
180
What is a **key disadvantage** of gas dilution methods compared to body plethysmography?
Only measures **communicating gas** (i.e. not trapped gas)
181
How is **body plethysmography** used to measure **FRC**?
* Subject sits in an **airtight chamber** that measures pressure, flow, and volume changes.
* While breathing, a shutter drops across the breathing tube.
* The subject makes respiratory efforts against the **closed shutter**, causing chest volume to expand.
* This increases chest volume, slightly reducing box volume and increasing box pressure.
* The change in lung volume is deduced using **Boyle's law** applied to box pressure/volume changes.
182
What determines **FRC**?
Balance between **lung recoil** and **thoracic cage** expansion.
183
What **increases** FRC?
* Standing
* COPD
* Asthma
* PEEP
184
What **reduces** FRC?
* Supine position
* General anaesthesia
* Pregnancy
* Obesity
185
What is **closing capacity**?
The volume at which the **small airways begin to collapse** and close off
If FRC is less than closing capacity, areas of the lung will be perfused but not ventilated at FRC (resulting in shunt)
186
What is **lung compliance**?
Change in **lung volume per unit** change in transpulmonary pressure.
## Footnote
Specific compliance is compliance divided by FRC (compensates for different body sizes).
187
What is a **pressure-volume curve** for the lung?
A graphical representation showing the relationship between **lung volume** and the **pressure applied to it**, indicating **lung compliance**.
## Footnote
The slope of the curve represents compliance, which is typically around 200 mL/cm H2O.
188
Why do the lungs demonstrate **hysteresis**?
**Hysteresis** is the difference in pressure-volume relationship during inflation vs. deflation. At a given lung volume, pressure is higher during inflation than deflation due to **surfactant** effects on surface tension.
## Footnote
During **inflation**, surfactant becomes more dilute, increasing surface tension and requiring higher pressures for further inflation. During **deflation**, surfactant becomes more concentrated, decreasing surface tension and needing less pressure to keep alveoli open. This dynamic change prevents small alveoli from collapsing and stabilizes pressures across different alveoli sizes.
189
What factors affect **lung compliance**?
Compliance is influenced by **lung volume** (compliance is highest at FRC), **lung elasticity** (loss of elastic tissue with ageing and emphysema increases compliance), and **surface tension** (the most important factor).
190
What does **ventilation** aim to control?
* pO2
* pCO2
* pH
191
What are the four main brainstem areas involved in the **control of respiration**?
* Dorsal respiratory group (medulla - inspiration)
* Ventral respiratory group (medulla - expiration)
* Pneumotaxic area (pons - arrest inspiration)
* Apneustic centre (prolongs inspiration)
## Footnote
NOTE: VRG contains the pre-Botzinger complex which is the pacemaker
192
Where does the **respiratory centre** receive inputs from?
* Peripheral and central chemoreceptors
* Mechanoreceptors in the lung and chest wall
* Higher CNS structures (including limbic system)
193
Describe the **actions** of the three different areas of the respiratory centre during breathing.
* **DRG** - has intrinsic automaticity responsible for basic respiratory rhythm, sends signals to diaphragm and intercostal muscles
* **Pneumotaxic centre** - can halt inspiration (fine-tuning)
* **VRG** - supports exhalation during exercise (quiet exhalation is passive)
194
How do the carotid body and aortic arch chemoreceptors **differ** in terms of what they **respond** to?
**Carotid Body**: pO2, pCO2 and pH
**Aortic Arch**: pO2 and pCO2
195
Which **nerves** transmit signals from the carotid body and aortic arch chemoreceptors?
**Carotid Body**: Glossopharyngeal Nerve
**Aortic Arch**: Vagus Nerve
196
What effect do volatile anaesthetics have on **peripheral chemoreceptors**?
Abolish their response to hypoxia.
197
What is the blood flow at the **carotid body**?
2 L per 100 g of tissue
## Footnote
NOTE: comprised of glomus cells containing dopamine.
198
Describe the functioning of **central chemoreceptors**.
* Located in the **ventral medulla**, they are surrounded by extracellular fluid.
* **pCO₂** diffuses across the blood-brain barrier, converting to H⁺ and bicarbonate in the CSF.
* As pH falls, **pH-sensitive neurons** are stimulated, increasing ventilatory drive.
199
Why does the **increase in ventilatory drive** due to hypercapnia abate after 48 hours?
**Increased bicarbonate transport** into the CSF will normalise the pH.
200
How does **pCO₂** affect ventilation?
* **Increased pCO₂** raises CSF H⁺ concentration, stimulating central chemoreceptors.
* This also activates peripheral chemoreceptors, enhancing minute ventilation.
* **Concurrent hypoxia** increases sensitivity to hypercapnia.
201
What factors can reduce the ventilatory response to **pCO₂**?
* Opiates
* Age
* Sleep
202
What are the effects of **high CO₂** on the body?
* **RESP**: increased minute ventilation
* **CVS**: vasodilation, myocardial depression, increased pulmonary vascular resistance
* **CNS**: narcosis, increased cerebral blood flow and ICP
* **RENAL**: compensation via bicarbonate retention
203
Describe the **ventilatory response** to hypoxia.
* Stimulates peripheral chemoreceptors (when PaO2 < 8 kPa)
* Hypercarbia augments the ventilatory response to hypoxia
204
At what **altitude** does atmospheric pressure halve?
5500 m (18,000 feet)
205
List the **physiological changes** that occur at altitude.
* Hyperventilation (due to hypoxic stimulation, hypocarbia leads to CSF alkalosis)
* ODC (moderate altitude shifts to right to facilitate unloading, at high altitude shifts to left to facilitate uptake)
* Polycythaemia (EPO secretion)
* CVS (increased HR and SV)
* Hypoxic pulmonary vasoconstriction
* Angiogenesis
206
How are **oxygen analysers** affected by altitude?
It assumes an atmospheric pressure of **101 kPa**.
## Footnote
For example, if the partial pressure of oxygen is 40 kPa in an atmospheric pressure of 80 kPa, it would display 40% rather than 50%.
207
Why is the output of a plenum vaporiser **not affected** by atmospheric pressure?
* Saturated vapour pressure is affected by **temperature** and not ambient pressure.
* The inspired percentage will increase but the partial pressure will remain the same.
* Clinical effect is dependent on **partial pressure**.
208
What mechanism underpins high altitude **cerebral oedema**?
Hypoxia leads to **cerebral vasodilation** which leads to **increased movement of fluid** through the blood-brain barrier.
209
By what mechanism does **acetazolamide** help manage mountain sickness?
**Increases bicarbonate excretion** via the kidneys, causing a **mild metabolic acidosis**. This boosts the ventilatory drive to breathe. Acetazolamide counteracts hypoxia-induced hyperventilation and maintains breathing drive, especially during sleep.
210
Why is **nifedipine** used in high altitude pulmonary oedema?
Inhibits hypoxic pulmonary vasoconstriction.
211
What occurs to **gas-filled cavities** during compression and decompression?
* Increasing pressure causes **compression** of gas-filled cavities during descent.
* This is manageable if there is enough time to equilibrate.
* Rapid ascent may not allow sufficient time for pressure differences to equilibrate, leading to **pneumothoraces** and **perforated** tympanic membranes.
212
Why is there a **limit** to how deep you can go with a snorkel?
**Increased dead space** means you will eventually start rebreathing
**Increased barometric pressure** will increase pulmonary vascular pressure but the alveoli are exposed to atmospheric pressure resulting in pulmonary oedema
213
Describe the pathophysiology of **decompression sickness**.
As per **Henry's law**, the solubility of a gas in solution is directly proportional to the partial pressure of the gas in equilibrium with the liquid.
At high pressures, **nitrogen becomes more soluble** in the blood. With rapid ascent, the nitrogen comes out of solution and forms bubbles which can cause microvascular complications (e.g. joint pain, visual disturbances).
214
Why is **heliox** better to use on deep dives?
**Helium is 50% less soluble than nitrogen** so dissolves less in tissues and is less likely to cause decompression sickness.
215
Why is **hyperventilating** before a breath-hold dive a bad idea?
Hyperventilating causes **hypocapnia**, reducing the drive to breathe. On descent, the subject relies on the hypoxic drive, risking profound hypoxia during rapid ascent as alveolar pO₂ decreases.
216
What are some indications for **hyperbaric oxygen therapy**?
* Gas lesions (e.g. air embolus or decompression sickness)
* Anaerobic infections
* Global hypoxia (CO poisoning)
* Inability to receive blood transfusions (at 3 atm dissolved O2 is enough to meet demands)
217
What are some ways of **assessing lung function**?
* **Bedside**: PEFR
* **Bloods**: ABG
* **Imaging/Special**: Spirometry, CXR, CT, cardiopulmonary exercise testing, CO diffusion capacity
218
What's an improvement in **bronchodilator reversibility testing** during **spirometry**?
200 mL if FEV1 < 1.5 L
15% if FEV1 ≥ 1.5 L
219
Describe obstructive and restrictive patterns on **spirometry**.
**Obstructive**
* FEV1 < 80%
* FVC reduced but less so than FEV1
* FEV1/FVC < 70%
**Restrictive**
* FEV1 < 80%
* FVC < 80%
* FEV1/FVC > 70%
220
Briefly describe **cardiopulmonary exercise testing**.
| (CPET)
* Non-invasive assessment of **cardiac** and **pulmonary** function (usually on cycle ergometer).
* Provides **breath-by-breath analysis** of gas exchange at rest and with increasing exercise.
* Provides information on airflow, O2 consumption, CO2 production and heart rate - this is used to determine **oxygen consumption** (including VO2 max) and anaerobic threshold.
221
What factors determine **DLCO**?
* Area
* Thickness
* Volume of blood in the pulmonary capillaries
222
What conditions are associated with a **raised** DLCO?
* Pulmonary haemorrhage (CO binds to this blood)
* Polycythaemia (more haemoglobin to bind to)
223
What conditions are associated with a **reduced** DLCO?
* Pulmonary hypertension
* Pulmonary embolism
* Emphysema
* Interstitial lung disease
## Footnote
NOTE: pulmonary hypertension means that vascular resistance is high and there's less capillary volume available to take up the gas.
224
What are the effects of general anaesthesia on **respiratory control**?
* BMR drops by 15% due to thalamic inhibition
* Response to hypercapnia is blunted
* Response to acidosis and hypoxia is more or less abolished
225
What are the effects of **general anaesthesia** on **lung mechanics**?
* **Decreased FRC**: reduced compliance
* **Bypassed humidifying mechanisms**: dry mucous membranes
* **Pulmonary vascular resistance**: increased West Zone 1
* **Glottis bypassed**: reduced intrinsic PEEP
226
What are the effects of **general anaesthesia** on gas exchange?
* **Atelectasis** can cause V/Q mismatch.
* **PEEP** may reduce blood flow in certain areas (more West Zone 1).
227
How does ventilation **differ** in the **lateral position** for spontaneous vs. mechanically ventilated patients?
**SPONTANEOUS**: dependent lung is better ventilated due to gravity's effect on compliance.
**MECHANICAL**: non-dependent lung is better ventilated because of lower resistance.
## Footnote
Blood flows preferentially to the dependent lung.
228
What respiratory changes occur during **exercise**?
Increase in **minute ventilation** due to afferent impulses from muscle proprioceptors.
**Oxygen consumption** rises until VO₂ max.
229
# Define:
VO₂ max
Maximum oxygen a subject can utilize to **produce ATP for exercise** (best index of cardiopulmonary fitness).
230
What is the **respiratory exchange ratio**?
| (RER)
RER = VCO₂ / VO₂
## Footnote
Represents metabolic gas exchange and depends on the fuel used (approximately 1.0 with carbohydrates, rising to 1.0 as anaerobic threshold is reached).
231
What is **standard bicarbonate**?
Represents the **metabolic component** of acid-base balance, independent of respiratory effects.
Assumes a **pCO₂ of 5.3**, **Hb of 5 g/dL**, and **temperature of 37°C**.
## Footnote
This Hb value adjusts for the lower buffering capabilities of plasma.
232
What is a **Siggaard-Andersen** diagram?
Plots **pH against bicarbonate** with lines for pCO₂, allowing quick assessment of **metabolic vs respiratory** components in acid-base disorders.
233
What compensatory mechanisms exist to **restore acid-base balance**?
* Intracellular buffering (bicarbonate, haemoglobin, phosphate)
* Respiratory compensation
* Renal compensation
234
How does **metabolic compensation** for **respiratory acidosis** occur?
Increased PaCO₂ in renal tubular cells leads to **H⁺ ion secretion** and **bicarbonate reabsorption**. This process takes 2-3 days.
## Footnote
Bicarbonate is regenerated by excreting H⁺ with ammonia and phosphate in urine.
235
What is the **anion gap**?
**Difference between measured cations and anions** (due to unmeasured anions like lactate, ketones, phosphates, and sulfates).
## Footnote
AG = (Na + K) - (HCO₃ + Cl)
Normal: 10-20 mmol/L
Unmeasured anions cause secondary bicarbonate loss, raising the anion gap.
236
List some causes of **high anion gap** metabolic acidosis.
* Ketoacidosis
* Lactic acidosis
* Uraemia
* Toxins (e.g. ethylene glycol, methanol)
237
What is a **buffer titration curve**?
* Plot of **pH vs amount of acid/base** added to a buffer solution.
* Buffering capacity is best when pH is around pKa.
238
What are the **main buffer systems** in the body?
* Bicarbonate (60%)
* Haemoglobin (imidazole groups of histidine can accept H+) 30%
* Plasma proteins (7%)
* Phosphate (3%)
* Urinary buffering
239
What's the **difference** between open and closed buffers?
**Closed**: fixed buffer components (e.g., haemoglobin), limited capacity.
**Open**: one component can be removed or replenished (e.g., bicarbonate, where CO₂ is regulated by the lungs).
240
Why is carbon dioxide **more soluble** in water than oxygen?
Carbon dioxide is a **polar gas**.
241
Explain how the **Severinghaus** electrode works.
**Modified glass electrode**
Blood flows across a CO₂-permeable membrane, allowing CO₂ to diffuse into a sodium bicarbonate buffer solution with glass and reference electrodes. CO₂ reacts with water to form H⁺ and HCO₃⁻. The H⁺ accumulates on the **pH-sensitive glass**, creating a potential difference proportional to CO₂ concentration.
242
How thick is the **alveolar-capillary barrier**?
200 nm
## Footnote
NOTE: surface area of alveoli is 70 m2 (size of badminton court)
243
Under what conditions can oxygen transfer become diffusion-limited instead of perfusion-limited?
Oxygen transfer can become diffusion-limited when the **alveolar-capillary membrane is thickened**, during **exercise** when blood transit time is reduced, or at **high altitudes** where lower atmospheric pressure decreases the partial pressure gradient for oxygen diffusion.
## Footnote
These conditions hinder the ability of oxygen to equilibrate between the alveoli and blood effectively.
244
What is the role of **PaCO₂** in the alveolar gas equation?
PaCO₂ divided by R indicates the **amount of O₂** removed by metabolism. It also reflects alveolar ventilation, accounting for hyper- or hypoventilation.
245
What are the **effects of airway devices** on the respiratory system?
* Loss of humidification
* Loss of physiological PEEP (with ETT)
* Increased work of breathing (worse with ETT than LMAs, due to radius)
* Increased dead space (requires greater minute ventilation)
* Airway irritation (laryngospasm, bronchospasm)
246
Describe the **effects of general anaesthesia** on respiratory dynamics.
* **FRC**: reduced due to positioning (supine/lithotomy) and relaxation of chest wall muscles, decreases compliance
* **ATELECTASIS**: absorption (due to high FiO2) and compression (reduced diaphragm tone and abdominal contents)
* **VQ MISMATCH**: positive pressure can generate west zone 1 in lung apices, impaired hypoxic pulmonary vasoconstriction
247
How much **carbon dioxide** can the body store?
120 L
Compared to 1.5 L for oxygen.
248
What are the components involved in the **control of ventilation**?
* **SENSORS**: Peripheral and central chemoreceptors, pulmonary stretch receptors (Hering-Breuer), irritant receptors (including J receptors), joint proprioceptors.
* **CONTROL CENTRE**: Pons and medulla.
* **EFFECTORS**: Muscles of respiration.
249
List some causes of **decreased respiratory compliance**.
* Supine
* Atelectasis
* Pulmonary oedema (increased surface tension)
* Pregnancy
* Pulmonary fibrosis
* Extremes of lung volume
* Chest wall rigidity/deformity
* Obesity
250
# Define:
hysteresis
A measurement differs depending on whether it is **rising or falling**.
251
What are the **two main forms of work** during breathing?
* **Elastic (65%)**: Overcomes elastic forces of chest wall/lung/surface tension; some stored as potential energy for expiration.
* **Resistive (35%)**: Work against friction (tissue and airflow).
## Footnote
NOTE: Usually <2% of BMR.
252
How does anaesthesia affect **airway resistance?**
* Lower lung volume (due to supine position, loss of muscle tone)
* Partial airway collapse increases resistance (if unintubated)
* Airway devices can increase resistance (ETT has smaller diameter than trachea)
* Anaesthetic circuits (e.g filter) increases resistance, turbulent flow from angle pieces
* Increased dead space requires increased minute ventilation
* Increased density and viscosity of anaesthetic vapours
253
What are the **functions** of the respiratory system?
* Gas exchange
* Acid-base balance
* Immunity (alveolar macrophages, IgA)
* Endocrine (ACE, inactivation of noradrenaline, serotonin, prostaglandins and acetylcholine)
* Inflammation (synthesis of histamine, endothelin, adenosine, prostaglandins)
* Drug metabolism (lidocaine, fentanyl, noradrenaline)
254
How is **VO₂** calculated?
VO₂ = CO x (CaO₂ - CvO₂)
## Footnote
Usually around 250 mL/min at rest, increasing to 5000 mL/min during exercise.
255
What is the normal oxygen delivery **at rest**?
~1000 mL of O2 per minute
256
Describe the **anaerobic threshold** in terms of **VO₂** and **DO₂**.
Anaerobic threshold occurs when **VO₂ exceeds DO₂**, requiring anaerobic mechanisms.
257
What are the main parts of the body affected by **oxygen toxicity**?
* **Lungs (Lorraine Smith)**: absorption atelectasis, lung inflammation, fibrosis, impaired gas exchange
* **CNS (Paul Bert)**: seizures, coma
* **Retina**: retinopathy of prematurity
## Footnote
NOTE: Caused by reactive oxygen species affecting nucleic acids and proteins.
258
What are the most important **antioxidant** systems in the body?
* Glutathione
* Catalase
* Superoxide dismutase
## Footnote
NOTE: ROS is needed for macrophage/neutrophil function, generally need pO2 > 50 kPa to cause oxygen toxicity.
259
What is the **interaction** between **bleomycin** and **oxygen therapy**?
Bleomycin can cause **pulmonary fibrosis**. Patients receiving **oxygen therapy after bleomycin** are at increased risk of life-threatening pulmonary fibrosis.
260
Outline the **oxygen stores** in the body.
* **Blood** (850 mL)
* **Myoglobin** (250 mL)
* **Lungs** (450 mL breathing room air at sea level)
261
How does pulmonary vascular resistance **compare** to systemic vascular resistance?
**PVR**: 160 dyn.s/cm-5
**SVR**: 1600 dyn.s/cm-5
262
How does an increase in mean pulmonary artery pressure cause a **decrease** in pulmonary vascular resistance?
* Recruitment: collapsed pulmonary capillaries will **re-open**.
* Distension: further **distension** of open pulmonary capillaries.
263
What are the main factors that affect **pulmonary vascular resistance**?
* Pulmonary artery pressure (distension and recruitment means PVR decreases as PAP increases)
* Lung volumes (resistance lowest at FRC)
* Hypoxic pulmonary vasoconstriction
264
How does **pulmonary vascular resistance** change with lung volume?
Pulmonary vascular resistance **decreases as lung volume increases** due to the recruitment and distension of pulmonary capillaries.
## Footnote
This relationship is important for optimizing gas exchange in the lungs.
265
What can **enhance** hypoxic pulmonary vasoconstriction?
Hypercapnia and Acidosis
266
What can **reduce** hypoxic pulmonary vasoconstriction?
* Alkalosis
* Hypocapnia
* Volatile anaesthetics
* Vasodilators (e.g. nitric oxide, nitrates)
* Bronchodilators
267
What are the two main forms of pathological shunt?
* **Intrapulmonary**: perfusion of alveoli that cannot take part in gas exchange (e.g. pneumonia, pulmonary oedema)
* **Extrapulmonary**: right to left intra-cardiac shunt (e.g. Eisenmenger), patent ductus arteriosus
268
How is **CcO₂** determined in the shunt equation?
Use the alveolar gas equation to find **PAO₂**, then apply it in the oxygen content equation, assuming 100% hemoglobin saturation to calculate **CcO₂**.
269
What is the **relationship** between the lung's tendency to recoil inwards and the chest wall's tendency to recoil outwards?
The **lung** tends to **recoil inwards** due to elastic recoil, while the **chest wall** tends to **recoil outwards** due to its structure and shape.
## Footnote
This balance creates the intrapleural pressure necessary for lung inflation during breathing.
270
What is the **flow-volume loops** for fixed and variable **extra-thoracic airway obstruction**.
* **Fixed** (e.g., tracheal stenosis): blunted inspiratory and expiratory limbs.
* **Variable** (e.g., vocal cord palsy): negative pressure pulls the lesion inwards, obstructing inspiratory flow; expiration pushes it outwards.
271
How does the **oxygen dissociation curve** change with altitude?
* **Acute**: hyperventilation leads to alkalosis, which leads to leftward shift
* **Chronic**: increased 2,3-DPG shifts curve to right
272
What are some **hazards** of high altitude?
* Hypoxia
* Increased risk of thrombotic events
* Hypothermia (increased evaporative losses due to low humidity)
* Increased solar radiation (sun burn)
273
When does surfactant start production in utero, and when are the lungs fully mature?
Surfactant production starts at **24 weeks**; lungs are fully mature by **35 weeks**.
274
Describe how the **oxygen dissociation curve** shifts at altitude.
* **Initially LEFT**: hyperventilation causes low pCO₂ and high pH.
* **Then RIGHT**: red cells increase 2,3-DPG production.
275
What stimulates **2,3-DPG** production in red cells?
Low oxygen availability (e.g., hypoxia, anemia) increases glycolysis.
Other triggers: pyrexia, thyrotoxicosis.
276
What is **transpulmonary** pressure?
The pressure difference between the **alveolus** and the **pleura**.
277
How does **respiratory compliance** compare to lung compliance?
Respiratory compliance is the compliance of the lung-chest wall system, which is lower than lung compliance (around 100 mL/cm H₂O).
**1/RC = 1/LC + 1/TCC**
278
What are the consequences of a **lack of surfactant** in the alveolus?
Increased surface tension leads to **higher pressures** needed to inflate smaller alveoli (lower compliance).
## Footnote
Smaller alveoli empty into larger ones.
Transudation of interstitial fluid into the alveolus.
279
How is **static compliance** measured?
Measured during inspiratory hold (no airflow):
**Compliance** = Tidal Volume / (Pplat - PEEP)
## Footnote
NOTE: Dynamic compliance is lower than static compliance due to airway resistance.
280
What is the **difference** between static and dynamic hysteresis?
* **Static**: due to viscous resistance of surfactant and lung parenchyma.
* **Dynamic**: related to airway resistance; compliance is lowest at the start and end of inspiration due to increased airflow and turbulence.
281
What are the key components of the **lung's immune function**?
* Mucociliary escalator
* Alveolar macrophages
* IgA
282
What can impair **mucociliary** function?
* **Patient**: smoking, cystic fibrosis, Kartagener syndrome
* **Anaesthetic**: volatile agents, dry inspired gases
283
What does the **Stewart acid-base** model state about acid-base balance?
Acid-base balance is determined by three variables: **pCO2, strong ion difference, and total weak acids** (e.g., plasma proteins).
## Footnote
Bicarbonate is considered a dependent variable in this model.
284
What is the usual **difference** between ETCO₂ and PaCO₂, and what causes it?
Typical difference is about **0.5 kPa**, mainly due to ventilation-perfusion (V/Q) mismatch.
## Footnote
This difference can indicate issues with gas exchange in the lungs.
285
By how much does a **tracheostomy** reduce dead space in an adult?
75-100 mL
286
What is each **heme molecule** composed of?
**Protoporphyrin** ring (four pyrrole rings) and iron in its ferrous (Fe²⁺) state.
287
List three forms of **haemoglobin**.
1. **Haemoglobin A**: 2 alpha and 2 beta
2. **Haemoglobin A2**: 2 alpha and 2 delta
3. **Haemoglobin F**: 2 alpha and 2 gamma
288
Describe the effect of **carbon monoxide** binding to **haemoglobin** on oxygen affinity.
Binding changes the conformation of haemoglobin making it **less likely to release oxygen** that is already bound (i.e. the oxygen dissociation curve is **shifted to the left** meaning that the affinity is increased).
289
What is the **critical temperature** of oxygen?
-118 degrees
290
Briefly explain how a **pulse oximeter** works.
* Red (660nm) and infrared (940nm) LEDs blink on and off 30 times per second from one end of the pulse oximeter.
* A photoreceptor on the other end will detect light that passes through the tissue in between.
* Oxygenated Hb absorbs infrared light to a greater extent than deoxygenated Hb. The degree of absorption of these two frequencies is used to compute the oxyhaemoglobin saturation.
291
What is the **saturated vapour pressure** of water at 37 degrees?
6.3 kPa
292
What is **surface tension** and what causes it?
A physical property of liquids that describes the **elastic-like force** at the surface, which allows it to **resist external force**.
## Footnote
This phenomenon occurs due to cohesive forces between liquid molecules, particularly in water, where hydrogen bonds play a significant role.
293
Derive how the work done by a ventilator is equal to **pressure x volume**.
* Work Done = Force x Distance
* Force = Pressure x Area
* Work Done = Pressure x Area x Distance
* Volume = Area x Distance
* Work Done = Pressure x Volume
294
What are the **five classes** of **pulmonary hypertension**?
1. Idiopathic
2. Secondary to left-sided heart disease
3. Secondary to chronic hypoxia or lung disease
4. Secondary to chronic thromboembolism
5. Rarer causes.
295
What changes occur in **stored blood**?
* Increased K+ (from cell death)
* Fall in pH (from cell death)
* Fall in 2,3-DPG leads to left shift in oxyhaemoglobin curve
296
Which nerve roots provide **sympathetic innervation** to the bronchi?
T2-T4
## Footnote
There are also parasympathetic fibres from the vagus nerve that form a posterior pulmonary plexus.
297
What is the **pKa** of the carbonic acid-bicarbonate and phosphate buffer systems?
* Carbonic Acid: **6.1**
* Phosphate: **6.8**
298
How is the **diffusion capacity** of the lung measured using the **carbon monoxide breath hold method**?
* **DLCO** quantifies CO transfer from alveoli to blood per minute per mmHg of mean alveolar CO partial pressure.
* The patient inhales a gas mix with ~0.3% CO and 10% helium to total lung capacity, holds breath for 10 seconds, then exhales.
* Helium dilution estimates alveolar volume, while the fall in CO over time calculates CO uptake (**V̇CO**).
* Mean alveolar CO pressure (**P̄ACO**) is estimated from remaining CO concentration, and:
* **DLCO** = **V̇CO** / **P̄ACO**
299
What is **West Zone 4**?
Interstitial pressure is higher than alveolar and venous pressure (but lower than arterial pressure).
300
List types of **reactive oxygen** species in the body.
* Superoxide anion (O₂⁻)
* Hydrogen peroxide (H₂O₂)
* Hydroxyl radical (OH)
301
What are barotrauma, volutrauma and atelectrauma?
* **Barotrauma** is lung injury caused by excessive airway pressure, leading to **alveolar rupture** and air leak (e.g., pneumothorax).
* **Volutrauma** is injury caused by over-distension from excessive tidal volumes, triggering **inflammatory** damage and **increased alveolar permeability** without necessarily high pressures.
* **Atelectrauma** is lung injury caused by **repeated collapse and reopening** of alveoli, leading to **shear stress and inflammation** at the alveolar interface.
302
What does the **Henderson-Hasselbalch** equation show?
It relates pH to the **ratio of a weak acid to its conjugate base**, indicating acid-base balance.
303
What is the **difference** between aerobic threshold, anaerobic threshold and VO2 max?
* **Aerobic Threshold**: The exercise intensity where lactate first begins to rise above baseline but is still cleared easily.
* **Anaerobic Threshold**: Aerobic metabolism is no longer sufficient so anaerobic processes rapidly increase, leading to accumulation of lactate.
* **VO₂ max**: The maximum oxygen consumption at peak exercise, where further effort cannot increase VO₂.
Primary FRCA
flashcards
Decks in class (17)
# Cards
-
Anatomy for Anaesthesia223
-
Physiology: Respiratory303
-
Physiology: Cardiovascular179
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Physiology: Renal, Hepatic & GI63
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Physiology: Neuro, Endo, & Haem237
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Pharmacokinetics and Pharmacodynamics213
-
Pharmacology: Inhalational & Intravenous Agents232
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Pharmacology: Analgesics & Muscle Relaxants160
-
Pharmacology: Emergency & Miscellaneous Drugs251
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Part 1: Physics & Equipment242
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Part 2: Physics & Equipment227
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Part 3: Physics & Equipment232
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Part 4: Physics & Equipment217
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Statistics & Evidence-Based Practice36
-
Part 1: Applied Clinical Anaesthesia165
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Part 2: Applied Clinical Anaesthesia169
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Part 3: Applied Clinical Anaesthesia157
