Respiration Flashcards
1
Q
what are the two types of respiration?
A
- Internal respiration
- within the cell
- CO2 is produced: glycolysis, Krebs cycle
- O2 is consumed: oxidative phosphorylation - External respiration:
- Ventilation
- exchange and transport of gases around the body
2
Q
what does respiration depend on?
A
diffusion:
- equilibrium is related to distance
- movement of ventilation provides maintenance of diffusion gradients
- mitochondria inside a cell, based in a solution with dissolved gases:
- solution outside: high O2, low CO2
- solution inside: low O2, high CO2
- this simple diffusion cannot work for longer distances: multicellular organisms
3
Q
what is the overview of the respiratory system?
A
- lungs: gets gases into/out of the body
- CVS: distributes gases to working tissues via capillaries, and takes waste products to lungs
- heart: equibriliates oxygen in blood
- deoxy blood enters left side to pulmonary circulation to be oxygenated
- oxy blood enters right side to systemic circulation to be distributed to body
- blood deposits O2 and takes up CO2 to return to lungs for exit
4
Q
what are the 2 sections of the lungs?
A
- conducting zone
2. respiratory zone
5
Q
what is the conducting zone of the lungs?
A
- transports gases to and from the respiratory zone
- contains mouth, nose, thoat and upper airways
- 23 sets of continually branching airways
- trachea enter lungs (branch 0)
- trachea form bronchi which divide to bronchioles (15-16 branch sets)
- bronchi supported with cartilage
- bronchioles are narrower and lack cartilage support, so depend on elastic tissue to prevent collapse
6
Q
what is the respiratory zone?
A
- respiratory bronchioles are lined in alveoli sacs (branch 23)
- many alveoli ducts and sacs with large SA for gas exchange
7
Q
what structures are in the conducting zone?
A
- nose
- nasopharynx
- mouth
- pharynx
- larynx
- trachea
- bronchial trees
8
Q
what is the function of the conducting zone?
A
- to condition the air for the respiratory zone
air must be:
- filtered: hairs trap particles to form turbulent condition
- warm: warmed up to body temp to decrease solubility of gases (cold gases cannot enter a warm blood supply as they form bubbles)
- humidify: becomes equilibrated and saturated with water vaper to prevent desecration of lower airways
9
Q
what is the structure of the bronchial wall?
A
- upper airways are reinforced with cartilage rings to prevent collapse and maintain diameter
- smooth muscle lines bronchi, under control of parasympathetic innervation for contraction/relaxation
- mucous glands: secretes mucus onto surface of bronchi to trap particles
- mucus lines lumen
- elastic tissue supports airways to prevent collapse`
10
Q
what makes up the respiratory epithelium?
A
Ciliated epithelia: lines lumen of airways
- beating of cilia helps direct mucus out of lungs to the throat and move particles with them
Goblet cells: secrete mucus and form mucus layer
Sensory nerve endings: between epithelial cells to detect noxious chemicals in airways
11
Q
what is the structure of the bronchioles?
A
- less than 1mm in diameter
- lacks cartilage support so is more subject to collapsing
- lined by respiratory epithelium
- tethering of elastic tissue keeps bronchioles open
- proportionally more smooth muscle than bronchi for control of airway diameter
12
Q
how do bronchioles collapse in emphysema?
A
- elastic tissue is broken down
- bronchioles are less stable and can collapse
13
Q
what is the structure of alveoli?
A
- large SA: 100m2
- fed from terminal bronchiole
- thin walled epithelial layer: short diffusion distance and large SA
- 3 million alveoli in the lungs
- lined by type 1 and type 2 pneumocytes
14
Q
what is the air-blood barrier?
A
- a sandwich created by flattened cytoplasm of type 1 pneumocyte and the capillary wall
- for gas exchange, 5 membranes must be crossed, including the apical-basal membranes and the epithelial membranes
- large SA for gas exchange: 50-100m2
- capillary network closely surrounds the alveoli to squeeze rbc close and minimise the diffusion distance
15
Q
what are the two processes of ventilation?
A
- inspiration
- expiration
both can be quiet (at rest) or forced (active e.g. during exercise)
16
Q
at what pressures does inspiration occur?
A
- when atmospheric pressure is greater than the pressure inside the alveoli
- allows air to move into the lungs down a pressure gradient
17
Q
at what pressures does expiration occur?
A
- when the pressure inside the alveoli is greater than the atmospheric pressure
- enables air to be forced out of the lungs down the pressure gradient
18
Q
what are the primary muscles of quiet inspiration?
A
- diaphragm: contracts and flattens
2. external intercostal muscles: contracts to move ribcage up and out
19
Q
what is the mechanism of quiet inspiration?
A
- primary muscles contract: diaphram flattens, external intercostals pull ribcage up and out
- this increases the thoracic and lung volume
- air movement follows the principles of Boyle’s law
- there is a reduction in pressure in the lungs, so air moves in, down the pressure gradient
20
Q
what are the muscles involved in forced inspiration? what are the actions of those muscles?
A
Primary muscles:
- diaphragm contracts and flattens
- external intercostals contract and move ribcage up and out
- overall increase in volume of thoracic cavity
accessory muscles:
- scalenes: attach to top of ribcage and contracts to lift ribs up and out
- sternocleidomastoids: attach to sternum and lift it muscles: move pelvic gurgle to expand ribcage
- upper respiratory tract muscles: reduce resistance to air flow
21
Q
what is the mechanism of quiet expiration?
A
- passive process using elastic recoil to pull inwards
- there are no primary muscles of expiration
- relaxation of external intercostals and diaphragm
- recoil of the lungs via elastic forces
- overall reduces lung volume, increases lung pressure
- gas is moved out of the lungs down the pressure gradient
22
Q
what are the accessory muscles of forced expiration?
A
Internal intercostals – contract to pull ribcage down and in
Abdominal muscles – push diaphragm up
Neck and back muscles – decrease ribcage lifting
23
Q
what is the pleural membrane? what is its role?
A
- lines chest walls and outside of lungs
- the pleural cavity is filled with secretions: fluid-filled space
- prevents lungs from sticking to chest wall and can slide past each other
- enables free expansion and collapse of lungs
- keeps lungs and chest walls in close connection but can move separately
24
Q
what happens to the elastic forces in the lungs and chest at rest?
A
they balance:
- the inward movement of the lungs and outward movement of the chest balance
- the pressure in the intrapleural space is less than atmospheric pressure
- allows air to flow in down a pressure gradient
- vacuum forms the negative pressure to allow lungs to maintain a normal resting volume
25
what is pneumothorax?
collapsed lung:
- trauma creates a breach in the chest wall
- this breaks the pleural membrane
- intrapleural space becomes in equilibrium with atmospheric pressure
- there is a loss of force that keeps the lungs inflated
- elastic forces of the lungs takes over, causing it to collapse
26
what is compliance?
a measure of elasticity/distensibility
- the ease with which lungs and thorax expand during pressure changes between intrapleural space and alveoli
low compliance = more work required to inspire
- e.g. pulmonary fibrosis means lung parenchyma is more rigid
high compliance = more difficulty in expiring (loss of elastic recoil)
- small change in pressure causes a big change in lung volume
- emphysema: loss in elastic recoil so harder to expire
27
how is compliance calculated?
C = change in volume / change in pressure
28
what are the effects of disease states on compliance?
pulmonary fibrosis:
- flatter curve as the lung volume doesn't increase as pressure increases in the lung
emphysema:
- steeper curve as a small change in pressure causes a large change in volume
29
what are the 2 major components of elastic recoil in the lung?
1. anatomical component
- elastic nature of the cells and ECM
2. elastic recoil
- due to the surface tension at the air-fluid interface
30
what are the effects of surface tension on lung compliance?
- when lungs are inflated with air, there is a small change in volume, and then a linear increase in volume
- lots of small airways at the start are closed
- before movement of air into the lung, the airways must overcome surface tension
- once they do this, they become more compliant and start opening
31
what is surface tension?
- it is caused by the difference in the forces on water molecules at the air-fluid interface
- the pressure in larger alveoli sacs is lower than the pressure in smaller sacs
- alveoli have different starting volumes:
- small alveoli have high pressure, large have low pressure
- air will flow from smaller alveoli to larger alveoli (high to low pressure)
- this leads to the collapse of smaller alveoli
32
what is laplace's equation and what does it describe?
the pressure inside a container (alveoli) is inversely proportional to the radius of the container:
pressure = 2 x Tension / radius
if the radius of the small bubble is half the radius of the big bubble, then the pressure needed to keep the small bubble inflated is 2x than that needed to keep open the large bubble
33
how is the problem of small alveoli collapsing due to surface tension overcame?
by surfactant lipoprotein
34
what is surfactant lipoprotein?
- produced by type 2 pneumocytes
- composed of lipids and proteins
- lipids partition into the air-fluid interface to reduce surface tension on smaller alveoli
35
what is the role of surfactant lipoprotein?
- prevents alveolar collapse by reducing surface tension
- regulates alveolar size as spread of surfactant shows the rate of inflation
- increases compliance and allows lungs to inflate ore easily
- prevents oedema: reduces fluid entering alveoli
36
what happens if production of surfactant decreases?
- lungs become harder to inflate
| - pneumonia
37
why do smaller alveoli have a higher density of surfactant than large alveoli?
- to balance pressures and surface tensions across all alveoli
- prevent collapsing
- prevent overinflation
38
what is the vital capacity?
- maximal volume of air that can be inhaled and exhaled
39
what is residual volume?
- volume of air in the lungs after maximal exhalation
40
what is total lung capacity?
- vital capacity + residual volume
41
what is the forced expiratory volume?
- maximal exhalation volume in 1 second
42
what is expiratory reserve volume?
- after expiration, how much air is left in the lungs down to residual volume
43
what is tidal volume?
- volume of air breathed in and out in a single breath
| - 500 ml at rest
44
what is inspiratory reserve volume?
- volume of air between tidal volume and vital capacity after inspiration
45
what is an equation for vital capacity?
VC = IRV + ERV + TV
46
what is functional residual capacity?
- total air left in the lungs after exhalation
| - ERV + RV
47
what is inspiratory capacity?
- after expiration, volume left in lungs up to total capacity
48
which lung volume cannot be measured by a spirometer?
residual volume
49
what is anatomical dead space?
- volume of the conducting airways
- at rest, approx 30% of inspired air volume (150ml)
- tidal volume 500ml at rest
50
what is physiological deadspace?
- volume of lungs not participating in gas exchange
- conducting zone + non-functional areas of respiratory zone
- normally the two values are almost identical
51
how do IRV and ERV change during exercise?
as tidal volume increases, ERV and IRV decrease
52
how is residual volume calculated?
helium dilution technique:
(Volume 1 x conc 1) + (volume 2 x conc 2) = RV
- known concentration of helium is in a container
- subject breathes and helium conc is measured
- helium conc is decreased as it has been diluted by being distributed in the lungs
53
what is the flow of air into/out of the lung proportional to?
- directly proportional to the pressure gradient
- indirectly proportional to resistance
Volume = (Palv - Patm)/R
54
what is Poiseuille's law?
determines the impact of resistance on flow:
- airway resistace is proportional to gas viscosity and the length of the tube
- airway resistance is inversely proportional to the 4th power of the radius
R = (8 x viscosity x length) / (pi x radius)^4
55
what can small changes in airway diameter cause?
- big impact on resistance and hence flow rate
| e. g. 10% reduction in radius increases resistance by 50%
56
what contributes to airway resistance in the lung?
- pharynx-larynx: 40%
- airways >2mm diameter = 40% (resistances in series RT=R1+R2+R3+….)
- airways <2mm diameter = 20% (resistances in series 1/RT= 1/R1+1/R2+1/R3...)
57
what is the airway resistance in a normal individual?
1.5cm H20 .s.litres-1
58
what factors impact airway resistance?
airway diameter:
- increased mucus secretion reduces airway diameter and increases resistance
- oedema: increased fluid retention in the lung tissue causes swelling and narrowing of airways, so increases resistance
- airway collapse: airway narrows and increases resistance
59
what are the 2 ways in which bronchial smooth muscle is controlled?
1. ANS
- parasympathetic: ACh is released from vagus, acts on mAChRs and causes CONSTRICTION
- sympathetic: NA is released from adrenergic
postganglionic neurons and leads to DILATION
2. Humoral factors:
- epinephrine circulating in blood: agonist leading to DILATION
- histamine: leads to CONSTRICTION
60
what is the composition of air?
- dry (atmospheric) and wet (trachea) at standard atmospheric pressure of 760mmHg
- as we breathe in, hair becomes humidified and saturated with water vapour
- mixtures of gases change as they become humidified
61
what is Dalton's Law?
- the total pressure of a mixture of gases is the sum of their individual partial pressures
- in the atmosphere, the components of air make up 760mmHg
- in the trachea, the components still make up 760mmHg, but they are saturated with water, so the pressures and nitrogen and oxygen are diluted/humidified
62
how can the amount of gases dissolved in solution be calculated?
Henry's Law:
- [Gas]dis = s x Pgas
- where s is the solubility coefficient (mM/mmHg) and P is the partial pressure of the gas
63
what is the amount oxygen that is dossolved in arterial blood and venous blood?
[Gas]dis = s x Pgas, where s is 0.0013mM/mmHg
- In arterial blood, PO2 is approx 100mmHg so [O2]dis = 0.13mM
- In mixed venous blood, PO2 is approx 40mmHg so [O2]dis = 0.05mM
64
what is the issue with oxygen being transported just by plasma?
- O2 has low solubility in saline: 0.003ml O2 per 100ml blood per mmHg
- under conditions where partial pressure of O2 is 100mmHg, plasma can carry 0.3ml O2 per 100ml
- at rest, with a cardiac output of 5000ml/s, plasma can provide at most 15ml O2/min
- the body requires 250ml O2/min, so plasma cannot deliver enough O2 alone
65
what solves this issue with limited O2 delivery by plasma?
haemoglobin
66
what is the structure of haemoglobin?
- tetrameric protein with 4 subunits and molecular weight of 68kDa
- each unit contains a haem unit and an a-globin chain
- dependent on Hb type there are different combinations of globin chains
- in adult Hb there are 2 alpha chains and 2 beta chains
- haem unit is a polyphyrin ring containing a single iron atom
- for O2 to bind to the iron it must be in the Fe2+ state
- enzyme methaemoglobin reductase converts Fe3+ back to Fe2+
67
what are the 2 states of haemoglobin?
1. Tense
- low affinity for O2, hard to bind to O2
2. relaxed state
- high affinity for O2, easy to bind to O2
68
what is the state of haemoglobin in the absence of O2?
- all 4 units are in a tense state
69
what is the state of haemoglobin in the presence of O2?
- if O2 binds to one of the units, all 4 units become relaxed via a conformational change
- this binding makes it easier for subsequent O2 molecules to bind to haemoglobin
70
what is the oxygen-haemoglobin dissociation curve?
- sigmoidal shaped curve: linked to change between tense and relaxed states
- at low partial pressure of O2, haemoglobin is in tense state, so 0% saturation of Hb
- as partial pressure of O2 increases, some Hb binds to O2 and flips to relaxed state
- this causes a rapid increase in saturation of Hb for O2
- Hb becomes saturated with O2 (97.5% saturated in arterial blood)
- in arterial blood, O2 content is 20ml pr 100ml blood
71
what is the saturation range of haemoglobin?
- 40mmHg in venous blood
| - 100mmHg in arterial blood
72
how does temperature affect the dissociation curve?
1. Warm blood (41C): curve shifts to the right
- haemoglobin, at any partial pressure, isn't able to carry as much O2
- saturation decreases, haemoglobin has a lowered affinity for O2 so unloads O2 at tissues easily
2. Cold blood (33C): curve shifts to the left
- Haemoglobin associates to O2 more tightly so can carry more O2
- harder to dissociate from O2
- to get the normal release of O2, partial pressure must drop in cooler blood conditions
73
what are the effects of pH and CO2 on the dissociation curve?
1. increase in partial pressure of CO2 causes acidification: curve shifts to the right (Bohr)
- haemoglobin is less efficient in carrying O2, so O2 dissociates easily to the tissues
2. decrease in partial pressure of CO2 causes alkalisation: curve shifts to the left
- haemoglobin readily associates with O2
74
what is the effect of 2,3 Diphosphoglycerate (2,3 DPG) on dissociation curve?
2,3 DPG = side product of glucose metabolism
1. increase in 2,3 DPG: curve shifts to the right
- 2,3 DPG binds to beta-globin chain and decreases association of O2 to haemoglobin
2. decrease in 2,3 DPG: curve shifts to the left
75
what are the implications of shifts in the dissociation curves?
In tissues undergoing active respiration:
- tissues generate heat: increased temperature
- increase in metabolism: increased CO2 production so decrease in pH
- production of lactic acid
all these factors cause a right shift of the curve
- causes decreased Hb affinity for O2, so more O2 is released to the tissues for respiration
76
what is the structure of foetal haemoglobin?
- in foetal Hb, the beta-globin chains are replaced by gamma-globin chains
- causes curve to shift to the left due to the lack of 2,3 DPG binding site
- higher affinity for O2 at any partial pressure
- helps foetal-Hb scavenge O2 from maternal circulation
- efficient uptake from mother circulation to foetal circulation
77
how is CO2 transported in blood?
- CO2 combines with water to form carbonic acid, catalysed by carbonic anhydrase
- carbonic acid then splits into bicarbonate and proton
- depending on the conditions, this reaction can move to the right further to produce carbonate and another proton
Blood carries CO2 as: dissolved CO2 -> carbonic acid -> bicarbonate -> carbonate -> carbamino compounds
- known as Total CO2
- critical for setting plasma pH 7.4
78
what is the transport process in blood of CO2?
1. CO2 crosses endothelial membrane of capillary and enters blood
2. 10% of that CO2 remains in the plasma: 6% is dissolved CO2, 3% is converted to bicarbonate by carbonic anhydrase, and 1% is bound to plasma proteins
3. 90% CO2 crosses the rbc membrane: small portion remains dissolved in cytoplasm, 24% binds to Hb to form carbamino compounds
4. when CO2 binds to Hb, it binds to other residues (not haem group)
5. this causes release of protons in rbc, making blood more acidic and cause Bohr shift
6. this causes unloading of O2 into the tissues
7. majority of CO2 in the rbc is converted to bicarbonate by type II carbonic anhydrase
8. bicarbonate is transported out of rbc by anion exchanger (Cl- enters, bicarbonate leaes)
9. bicarbonate is dissolved into the plasma
79
what is the majority of CO2 carried in the blood as?
bicarbonate
80
what happens to the transport process of CO2 at the lungs?
it is reversed:
- anion exchanger switches direction so that bicarbonate enters rbc and Cl- leaves
- bicarbonate is converted back to CO2
- CO2 leaves and moves across capillary endothelium into the alveoli
81
what are the two categories of lung disease?
1. obstructive: reduction in flow through the airways
2. restrictive: reduction in lung expansion
both reduce ventilation, and there can be a mixture of the two
82
what way can volume of air expired in a certain time be measured?
- lungs are inflated as much as possible, and vital capacity (VC) is exhaled
- measure forced expiratory volume (FEV)
- FEV is taken as a ratio of VC
- quoted as FEV1%: the % of VC that can be expired in 1 second
83
what are flow loops?
- Y-axis = air flow (how quickly air moves out of lungs)
- X-axis = volume in litres
- exhalation is at the top (FEV): rapid increase in flow out of lungs to reach peak expiratory flow, then gradual drop in flow rate as lungs empty
- inhalation is at the bottom, decrease in flow as air moves in
84
what are obstructive lung diseases?
- the result of the narrowing of airways
- narrowing could be due to:
- excess secretions of mucus
- bronchoconstriction: asthma (smooth muscle
contracts to reduce diameter and increase
resistance)
- inflammation: oedema causes swelling and
reduces diameter
- in all cases there is an increased resistance to air flow
85
what is the spirometry of an obstructive disease?
in normal cases:
- people can breathe out 90-100% of VC in 1 second
- FEV1:VC = 90%
in obstructive disease:
- reduction of FEV1 to below 80% of VC
- FEV1 < 80% VC
86
what do volume-time curves display about obstructive diseases?
- total VC is unchanged, it just takes longer for that volume of air for that volume ti be exhaled
- volume exhaled after 1 second is reduced
- FEV1:VC is reduced
87
what do flow-time curves display about obstructive diseases?
in normal cases:
- there is a linear decline in flow after peak expiration
in obstructive disease:
- there is a sharp fall in flow-rate to create a concave shape to the curve
the initial flow and peak flow is similar in normal and obstructive cases
88
what are examples of obstructive diseases?
Chronic Bronchitis: persistent cough and excessive mucus secretion
- 3 consecutive months in last 2 years
asthma: inflammatory disease
Chronic Obstructive Pulmonary Disease (COPD)
- structural changes
Emphysema: lost of elastin
- subtype of COPD
89
what is asthma?
- sufferer has hyperactive airways
- triggers can be atopic/extrinsic (allergies) or non-atopic/intrinsic (respiratory infections, cold air, stress, exercise, inhaled irritants, drugs)
- caused by movement of inflammatory cells to the airways and releasing inflammatory mediators such as histamine, which causes bronchoconstriction of smooth muscle
90
what are asthma treatments?
short-term: short-acting beta-adrenoreceptor agonists
- salbutamol -> causes dilation of airways by acting on smooth muscle
long-term: inhaled steroids
- glucocorticoids such as beclomethasone act to reduce inflammatory responses
- long-acting beta-adrenoreceptor agonists
91
what are restrictive lung diseases?
- reduced chest expansion due to chest wall abnormalities or muscle contraction deficiencies
- loss of compliance (fibrosis): increased collagen (fibrous tissue)
- occurs due to aging and exposure to environmental factors
92
what is the spirometry of a restrictive lung disease?
- large reduction in VC compared to predicted VC
93
what do volume-time curves display about restrictive diseases?
- there is a reduction in forced VC (FVC)
- the curve is shifted down/compressed
- reduction FVC
- FEV1% remains unaltered, or can even increase
- FEV1%:VC remains high
94
what is asbestosis?
- slow build-up of fibrous tissue leading to a loss of compliance
- body recognises asbestos particles as foreign, and macrophages attack but cannot breakdown asbestos
- leads to build-up of fibrous tissue around asbestos particles
95
how is the pattern of breathing regulated?
- the basic respiratory rhythm is generated by the pre-Botzinger complex centre in the medulla
- breathing is an involuntary mechanism but can be altered consciously by hyperventilation or breath-holding
- these temporary controls can be overriden if required
96
will a lesion to the pons and medulla halt the breathing pattern?
no, an individual will still produce a basic breathing pattern
if the lesion is below the medulla, the pattern will be lost and breathing will halt
97
what are the 3 medullary centres involved in respiration?
1. pre-botzinger complex
2. dorsal respiratory group
3. ventral respiratory group
all send signals down the phrenic nerve to the diaphragm to generate the breathing pattern
98
what is the role of the pre-botzinger complex?
- generates the breathing pattern
| - next to the VRG
99
what is the role of the DRG in respiration?
- controls quiet respiration by sending signals to inspiratory muscles
- receives signals from pre-Botzinger complex
- spontaneously active
- controls the diaphragm
100
what is the role of the VRG in respiration?
- controls forced inspiration and forced expiration
101
what is the role of the Pons in the breathing?
2 centres in the Pons send stimuli to the medulla to regulate rate and depth of breathing:
1. Pneumotaxic centre: increases rate by shortening inspirations
- inhibitory effect on inspiratory centre
2. Apneustic centre: increases depth and reduces rate by prolonging inspiration
- stimulates respiratory centre
102
what is the Hering-Breuer reflex?
negative feedback loop:
1. stretch receptors in lung send signals to medulla to limit inspiration and prevent over-inflation of the lungs
2. inspiratory centre generates pattern, sending signal down phrenic nerve
3. signal causes contraction of diaphram
4. this causes expansion of lungs which activates stretch receptors
5. stretch receptors send signal via vagus to inspiratory centre
6. if signal is too high, inspiration is inhibited and expiration is promoted
103
how do chemoreceptors monitor breathing?
1. central chemoreceptors: monitor conditions in cerebrospinal fluid and sense CO2 and pH
- indirect response to a rise in CO2
- stimulation leads to increase in ventilation to remove CO2 and rebalance pH
2. Peripheral chemoreceptors: respond to increase in CO2, decrease in pH and decrease in O2
- located in aortic arch
- mainly respond to hypoxic conditions e.g. high altitude
- stimulation leads to an increase in ventilation
104
what is the overall control of the breathing pattern by the medulla and pons?
1. In medulla is the pre-Botzinger complex, the central pattern generator, which sends out signals through DRG and VRG to control inspiration and expiration via diaphragm, intercostals and abdominals.
2. Input from pons modify the pattern generated from pre-Botzinger complex due to emotions, stress, pH and CO2 and O2 sensed by chemoreceptors.
