Physiology Flashcards
Internal respiration
The intracellular mechanisms which consumes O2 and produces CO2
External respiration
The sequence of events that lead to the exchange of O2 and CO2 between the external environment and the cells of the body
What are the 4 steps of external respiration?
- Ventilation
* The mechanical process of moving gas in and out of the lungs
- Ventilation
- Gas exchange between alveoli and blood
* The exchange of O2 and CO2 between the air in the alveoli and the blood in the pulmonary capillaries
- Gas exchange between alveoli and blood
- Gas transport in the blood
* The binding and transport of O2 and CO2 in the circulating blood
- Gas transport in the blood
- Gas exchange at the tissue level
* The exchange of O2 and CO2 between the blood in the systemic capillaries and the body cells
- Gas exchange at the tissue level

Boyle’s Law
As the volume of a gas increases the pressure exerted by the gas decreases
What must occur to the intra-alveolar pressure for air to flow into the lungs during inspiration?
It must become less than atmospheric pressure
How does the intra-alveolar become less than the atmospheric pressure during inspiration?
During inspiration the thorax and lungs expand as a result of contraction of inspiratory muscles. This creates a greater volume within the lungs, and therefore a decrease in pressure.
How does the movement of the chest wall expand the lungs without a physical connection?
-
1) The intrapleural fluid cohesiveness
- The water molecules in the intrapleural fluid (between the visceral and parietal pleura) are attracted to each other and resist being pulled apart
-
2) The negative intrapleural pressure
- The sub-atmospheric intrapleural pressure creates a transmural pressure gradient across the lung wall and across the chest wall (Pressure inside the lung is grearter than pleural cavity, so lungs push out and a tmopsheric pressure is higher than pleural cavity, so chest wall pushes in)

What is the most important respiratory muscle?
Diaphragm
True or False: Inspiration is an active process
True, it is dependent on muscle contraction which lowers the idntraalveolar pressure to fall pulling the air in down a pressure gradient

True or False: Expiration is an active process
False, it is a passive process brought about by relaxation of inspiratory muscles and elastic recoil which causes the intra-alveolar pressure to rise and force the air out

What happens in a pneumothorax in terms of ventilation?
It abolishes the transmural pressure gradient as puncture allows air to move air from the atmosphere into the pleural cavity. When the transmural pressure gradient is abolished, the lung collapses as there is nothing holding it to the pleural cavity anymore
Surface tension
In the alveoli attraction between water molecules at liquid air interface produces a force which resists the stretching of the lungs as the water molecules around the alveoli are attracted to each other so this tends to make the bubble smaller
Law of LaPlace
The smaller alveoli (with smaller radius - r) have a higher tendency to collapse
Surfactant
Complex mixture of lipids and proteins secreted by type II alveoli. It lowers alveolar surface tension by interspersing between the water molecules lining the alveoli. This prevents the alveoli from collapsing.
Respiratory distress syndrome of the new born
Developing fetal lungs are unable to synthesize surfactant until late in pregnancy, therefore premature babies may not have enough pulmonary surfactant. The baby makes very strenuous inspiratory efforts in an attempt to overcome the high surface tension and inflate the lungs.
Alveolar interdependence
If an alveolus starts to collapse then the surrounding alveoli are stretched and then recoil exerting expanding forces in the collapsing alveolus to open it again.

What are the overall forces acting on the alveoli?
.

What are the 3 main groups of muscles of exernal ventilation?
- Major muscles of inspiration
- Accessory muscles of inspiration
- Muscles of active expiration
Tidal Volume
Volume of air entering or leaving lungs during a single breath (500ml)

Inspiratory reserve volume (IRV)
Volume of air you can take in after you have already taken a normal breath (~3L)

Expiratory reserve volume (ERV)
Volume of air you can force out after already breathing out normally (~1L)

Vital Capacity (VC)
Maximum amount of air a person can expel from the lungs after a maximum inhalation (~4.5L)
( = Inspiratroy reserve volume +Tidal volume + expiratory reserve volume)

Residual Volume (RV)
Minimum volume of air remaining in the lungs even after a maximal expiration (~1200ml)

Functional Residual Capacity
The amount of air that is normally within your lungs at all timea after normal expiration (`~2.2L)
(Residual volume + expiratory reserve volume)

Total lung capacity
Total volume that the lungs can hold (~5.7L)
(This means that function residual capacity, is about half of the total capacity, so our lungs are half full at all times)

Forced vital capacity (FVC)
Maximum volume that can be forcibly expelled from the lungs following a maximum inspiration
FEV1
Forced Expiratory volume in one second
FEV1% = FEV1/FVC ratio
This is the percentage of the vital capacity which is expired in the first second of maximal expiration.
(In healthy patients the FEV1/FVC is usually around 70%)
What happens in obstructive diseases in terms of spirometry?
The FEV1 and FEV1/FVC% is lowered, FVC is low or normal

What happens in restrictive diseases in terms of spirometry?
With restrictive disease, the airways remain patent and are normal, however the issue is in the lung parenchyma so the FVC and FEV1 is reduced, but the FEV1/FVC% is normal

What is the equation for airway resistance?
Flow (F) = change in pressure (P)/Resistance (R)
Dynamic airway compression during expiration in normal people
The rising pleural pressure during active expiration compresses the alveoli and airway. Pressure applied to alveolus helps pushes air out of lungs, Pressure applied to airway is not desirable - tends to compress it. In nromal people the increased airway resistance causes an increase in airway pressure upstream. This helps open the airways by increasing the driving pressure between the alveolus and airway (i.e. the pressure downstream)

Dynamic airway compression in people with obstructuve disease
If there is an obstruction (e.g. asthma or COPD), the driving pressure between the alveolus and airway is lost over the obstructed segment. This causes a fall in airway pressure along the airway downstream, resulting in airway compression by the rising pleural pressure during active expiration. Therefore, diseased airways are more likely to collapse

Compliance
Measure of effort that has to go into stretching or distending the lungs during inspiration
What kind of conditons decrease pulmonary compliance and what are the consequences of it?
Pulmonary fibrosis, pulmonary oedema, lung collapse, pneumonia, absence of surfactant.
Decreased pulmonary compliance means greater change in pressure is needed to produce a given change in volume (i.e. lungs are stiffer). This causes shortness of breath especially on exertion.
Decrease pulmonary compliance may cause a restrictive pattern of lung volumes in spirometry
What kind of conditions cause increased pulmonary compliance and what are the consequences?
Compliance may become abnormally increased if the elastic recoil of the lungs is lost such as in emphysema.
Patients have to work harder to get the air out of the lungs – hyperinflation of lungs. Dynamic airway obstruction will also be aggravated in patients with obstructed airway and emphysema caused by COPD.
Pulmonary ventilation (L) =
= the volume of air breathed in and out per minute
= tidal volume (L/breath) x Respiratory Rate (breath/min)
(usually 6L/min)

True or False: Alveolar ventilation is less than pulmonaru ventilation
True, due to anatomical dead space (150ml)

Alveolar ventilation =
= the volume of air exchanged between the atmosphere and alveoli per minute
(= (tidal volume – dead space volume) x Respiratory Rate)
(usually around 4.2L/min)

Ventilation =
the rate at which gas is passing through the lungs.
Perfusion
the rate at which blood is passing through the lungs
Alveolar dead space
Ventilated alveoli which are not adequately perfused with blood
Physiological dead space =
the anatomical dead space + the alveolar dead space
How is ventilation matched to perfusion?
- Accumulation of CO2 in alveoli as a result of increased perfusion, decreases airway resistance leading to increased airflow (to then be able to shift the CO2)
- Increase in alveolar O2 concentration as a result of increased ventilation causes pulmonary vasodilation which increases blood flow to match larger airflow (to then get this O2 to the tissues)

What happens to pulmonary arterioles in areas of decreased O2?
The vasoconstrict, as you want the greatest bloody supply to be in areas of good ventilation
What 4 things influence the rate of gas exchange across alveolar membranes?
- Partial pressure gradient of O2 and CO2
- Dalton’s Law of Partial Pressures
- Diffusion coefficient for O2 and CO2
- Surface area of alveolar membrane
- Fick’s law of diffusion
- Thickness of alveolar membrane

Dalton’s Law of Partial Pressures
The Total Pressure exerted by a gaseous mixture = the sum of the partial pressures of each individual component in the gas mixture
(Thus if the total pressure of the gas mixture is 100 kPa; and 50% of the mixture is gas (1): the partial pressure for gas (1) is 50 kPa)
Alveolar gas equation
PaO2 = PiO2 - [PaCO2/0.8]
- PAO2 = Partial Pressure of O2 in alveolar air
- PiO2 = Partial pressure of O2 in inspired air
- atmospheric pressure – water vapour pressure = 760 – 47 mmHg = 713 mmHg at sea level
- PiO2 would then = 713 x 0.21 = 150 mmHg (as 21% of inspired air is O2)
- PaCO2 = Partial pressure of CO2 in arterial blood
- Normally 40mmHg
-
0.8 is the Respiratory Exchange Ratio (RER)
- (i.e. ratio of CO2 produced/O2 consumed for someone eating a mixed diet)
- PaO2 is therefore normally 100mmHg
How do you convert from mmHg (used in US) to kPa (used in UK)?
Divide mmHg by 7.5
True or False: Gases move from a low to high partial pressure gradient
False, they move from high to low. This is why oxygen moves from alveoli to blood and then blood to tissue, and CO2 moves from tissue to blood to alveoli

Diffusion coefficient of a gas
The solubility of gas in membranes
Which has a higher diffusion coefficient: CO2 or O2?
CO2 coefficient is 20x higher than that of O2, which is why there are equal levels of CO2 and O2 even though the partial pressure of O2 is much higher
What would a big gradient betweeb PAO2 and PaO2 indicate?
problems with gas exchange in the lungs or a right to left shunt in the heart
Fick’s Law of Diffusion
The amount of gas that moves across a sheet of tissue in unit time is proportional to the area of the sheet but inversely proportional to its thickness
How many times does the respiratory tree bifurcate in order to maximise surface area?
23 times

Conducting zone =
Area that moves air in and out with no respiration.
Bronchi > Terminal bronchioles
Respiratory zone
Area of the lungs that has active gas exchange
Respiratory bronchioles > Alveoli
What kind of cells make up the walls of the alveoli?
a single layer of flattened Type I alveolar cells
(responsible for gas exchange, Type II are involved in production of surfactant)
What are some of the non-respiratory functions of the respiratory system?
- Route for water loss and heat elimination
- Enhances venous return
- Helps maintain normal acid-base balance
- Enables speech, singing, and other vocalizations
- Defends against inhaled foreign matter
- Removes, modifies, activates, or inactivates various materials passing through the pulmonary circulation
- Nose serves as the organ of smell
How do you determine atmospheric oxygen partial pressure?
multiplying total/atmospheric pressure x % oxygen in atmosphere (then divide by 7.5 to get to kPa)
Henry’s law
The amount of a given gas dissolved in a given type and volume of liquid (e.g. blood) at a constant temperature is proportional to the partial pressure of the gas in equilibrium with the liquid.
This means that if the partial pressure in the gas phase is increased the concentration of the gas in the liquid phase would increase proportionally
What are the 2 main methods of oxygen transport?
- Dissolved oxygen (1.5%)
- Bound to haemoglobin (98.5%)
How much oxygen is dissolved in the blood in both resting and strenuous conditions?
- 3ml O2 per litre of blood at a PO2 of 13.3 kPa
- Under Resting conditions (cardiac output 5L/min): 15 ml/min of O2 is taken to tissues as dissolved O2
- At strenuous exercise (cardiac output of 30 L/min): 90 ml/min would be taken to tissues as dissolved O2
How much oxygen is bound to haemoglobin?
About 20 ml/100 ml (200 ml per litre) at a normal arterial PO2 of 13.3 kPa and a normal haemoglobin concentration of 15 grams/100 ml
What is the primary factor in determining the percentage saturation of haemoglobin with O2, and when is Hb nearly fully saturated?
PO2, and Hb is nearly fully saturated at a PO2 of 13.3kPa

Oxygen Delivery Index (DO2I) =
= Volume of gaseous oxygen pumped from the ventricle per minute per metre2
= CaO2 x CI
(ml/min/metre2)
- CaO2 = Oxygen content of arterial blood (ml/L)
- CI = Cardiac index (L/min/metre2)
- Cardiac output to the body surface area
Oxygen Content of Arterial Blood (CAO2) =
= 1.34 x [Hb] x SaO2
- One gram of Hb carry 1.34 ml of O2 when fully saturated
- [Hb] = haemoglobin concentration (gram/L)
- SaO2 = %Hb saturated with O2
What 4 things can impair the oxygen delivery to tissues?
- Decreased partial pressure of inspired oxygen
- Can be affected by altitude where the total pressure (atmospheric pressure) decreases
- Respiratory disease
- These can decrease arterial PO2 and hence decrease Hb saturation with O2 and O2 content of the blood
- Anaemia
- This decreases Hb concentration and hence decreases O2 content of the blood
- Heart Failure
- This decreases cardiac output
Co-operative binding
Binding of one O2 to Hb increases the affinity of Hb for O2
(This is why the oxygen saturation curve is sigmoid)
What shape is the oxygen dissociation curve?
Sigmoid
What is the significant of the oxygen dissociation curve being sigmoid?
- Flat upper portions means that moderate fall in alveolar PO2 will not much affect oxygen loading
- Therefore the upper parts are very protective
- Steep lower part means that the peripheral tissues get a lot of oxygen for a small drop in capillary PO2
What is the Bohr Effect and what conditions cause it?
Basically a shift to the right on the O2 Dissociation Curve means more O2 for the tissues. This shift can occur due to:
- Increased PCO2
- Increased [H+]
- Increased temperature
- Increased 2,3-biphosphiglycate

How does feotal haemoglobin structure differ from adult haemoglobin and what are the implications of this?
HbF has 2 alpha and 2 gamma subunits and HbF interact less with 2,3- Biphosphoglycerate in red blood cells.
Hence, HbF has a higher affinity for O2 compared to adult haemoglobin (HbA) means O2-Hb dissociation curve for HbF is shifted to the left compared to HbA.
Hb gives up the O2 less easily, this would allow O2 to transfer from mother to foetus even if the PO2 is low
Where is myoglobin present?
skeletal and cardiac muscles, not in the blood
How does myoglobin differ from haemoglobin?
- Only one haem group can bind to myoglobin, as opposed to 4 in Hb
- No cooperative binding of O2 (no increase in affinity for next O2 as O2 binds)
- Dissociation curve hyperbolic, rather than sigmoid
- Myoglobin only releases O2 at very low PO2
- Provides a short-term storage of O2 for anaerobic conditions

What are the 3 methods of Carbon Dioxide transport?
- Dissolved in solution (10%)
- As Bicarbonate (60%)
- As Carbamino compounds (bound to Hb) (30%)
Why is more carbon dioxide transported dissolved in the blood compared to oxygen?
Because CO2 is 20x more soluble than O2
How is CO2 formed into bicarbonate to be transported?
Carbon dioxide enters the RBCs when it enters the capillaries, where it forms bicarbonate
Bicarbonate is formed in the blood by:
- Dissolved CO2 reacts with water to form carbonic acid (H2CO3)
- Dissolved CO2 concentration is around 1000x greater than that of carbonic acid
- Then small amount ionises to bicarbonate and H+ ions

Which enzyme catalyses the conversion of CO2 to bicarbonate?
Carbonic anhydrase (CA)
What role does Hb play in the conversion of CO2 into bicarbonate for transport?
The hydrogen ions, formed from the dissociated carbonic acid, combine with the haemoglobin in the red blood cell. Here the haemoglobin acts as a buffer, as the histidine proteins of haemoglobin accept a proton.
By Le Chatelier’s principle, anything that stabilizes the proton produced will cause the reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for protons enhances synthesis of bicarbonate and accordingly increases capacity of deoxygenated blood for carbon dioxide.
How is CO2 bound to Hb for transport?
Carbamino compounds formed by combination of CO2 with terminal globin of haemoglobin to give carbamino-haemoglobin.
Haldane Effect
Removing O2 from Hb increases the ability of Hb to pick-up CO2 and CO2 generated H+.
Vice versa, increased O2 concentration reduces Hb affinity for CO2
Opposite to Bohr effect: increase in PCO2 causes a reduction in the affinity for O2 due to an increase in proton concentration
How do the Bohr and Haldane effects work together?
Bohr effect and the haldane effect work in synchrony to facilitate: O2 liberation and uptake of CO2 & CO2 generated H+ at tissues
Basically, the Bohr effect means that at the tissues, the higher CO2 concentration means that Hb loses its affinity for oxygen and drops it, making it available for tissues.
Whereas in the lungs, the Haldane effect means that the high O2 concentration means that it doesn’t pick up CO2 of H+, so they are expired instead
What is the major rhyhtm generator of respiration?
Network of neurons called the Pre-Botzinger complex in the respiratory centre of the medulla
What process gives rise to inspiration?
- Rhythm generated by Pre-Botzinger complex
- Excites Dorsal respiratory group neurons (inspiratory)
- Fire in bursts
- Firing leads to contraction of inspiratory muscles, leading to inspiration
- When firing stops, passive expiration occurs
What process gives rise to active expiration?
- Increased firing of dorsal neurones excites a second group: Ventral respiratory group neurones
- These excite internal intercostals, abdominals etc.
- Resulting in forceful expiration
What areas in the pons can modify the rhythm generated in the medulla and what effect do they have?
- Pneumotaxic Centre (PC)
- Apneustic Centre
Stimulation of the PC terminates inspiration, without it there is prolonged inspiration. Stimulation of the apneustic centre prolongs inspiration
Respiratory centres are influenced by stimuli from which areas?
- Higher brain centres e.g. cerebral cortex, limbic system, hypothalamus
- Stretch receptors in the walls of bronchi and bronchioles
-
Juxtapulmonary (J) receptors
- stimulated by pulmonary capillary congestion and pulmonary oedema (caused by e.g. left heart failure)
-
Joint receptors
- stimulated by joint movement
-
Baroreceptors
- increased ventilatory rate in response to decreased blood pressure
- Central chemoreceptors
-
Peripheral chemoreceptors
- These relate to chemical control of respiration
Hering-Breuer reflex
Pulmonary stretch receptors are activated during inspiration, and their afferent discharge inhibits inspiration to prevent hyperinflation
Only activated at large >1L tidal volumes
Where are the chemoreceptors of the body and what do they respond to?
- Peripheral chemoreceptors
- Carotid and aortic bodies
- Sense tension of oxygen and carbon dioxide; and [H+] in the blood
- Central chemoreceptors
- Situated near the surface of the medulla of the brainstem
- Respond to the [H+] of the cerebrospinal fluid (CSF)
What are the acute and chronic adaptations to high altitudes?
- Acute: hyperventilation & increased cardiac output
Chronic:
- RBC production (polycythaemia)
- increasesO2 carrying capacity of blood
- Increased 2,3 BPG produced within RBC
- O2 offloaded more easily into tissues
- Increased number of capillaries
- Blood diffuses more easily
- Increased number of mitochondria
- O2 can be used more efficiently
- Kidneys conserve acid
- arterial pH decreases