Block 4 - Respiratory Flashcards

Question

Draw a diagram of the carbon dioxide dissociation curve.

Answer 1

[see notes for answer]

Answer 2

o CO2 release from tissue / O2 release from Red cell: 1) CO2 dissolves into plasma & red cells along the partial pressure gradient. 2) Low tissue O2 favours CO2 carriage by blood (Haldane effect). 3) Carbamate reaction reduces HbO2 affinity (Bohr effect). 4) Carbonic anhydrase reaction generates carbonic acid which protonates. HCO3- leaves cells and maintains the inward CO2 gradient. 5) Increased red cell [H+] reduces HbO2 affinity by promoting Hb subunit interactions (Bohr effect).

Answer 3

O2 and CO2 define the ventilation-perfusion relationship in the lung (V/Q). 1) Oxygen equilibrates from alveolus to blood. 2) CO2 equilibrates from blood to alveolus. So O2 and CO2 partial pressure in the alveolus and arterial blood can be used to understand how lung ventilation is matched with perfusion of the lung. Why does this matter? - Major effect on aerobic performance - Major contribution to disease - Its adaptable -> changes in breathing and lung perfusion allow fine-tuning of O2 uptake and CO2 clearance from one environment to another.

Answer 4

Interplay between the local control of ventilation and perfusion within and between lung regions. Poor ventilation and large blood flow = need to reduce perfusion, hypoxia constricts pulmonary arterioles. Good ventilation and poor blood flow = need to reduce ventilation, low CO2 constricts bronchioles. Ventilation (V) refers to the flow of air into and out of the alveoli, while perfusion (Q) refers to the flow of blood to alveolar capillaries.

Answer 5

Carbonic anhydrase is an enzyme that facilitates the conversion between carbon dioxide (CO2) and water (H2O) to form carbonic acid (H2CO3) and its dissociative ions (HCO3− and H+). It plays a key role in regulating pH and aiding in the transport of CO2 in biological systems.

Answer 6

[see notes for answer]

Answer 7

Lung mechanics -> physical forces that influence breathing.

Answer 8

Mechanical properties of the lung that influence gas flow but which are independent of volume change. - Elasticity - Compliance - Surface tension

Answer 9

Elastance = change in pressure / change in volume The pleural sac links elastic forces in the chest wall and lung. Elastic forces link pleural pressure to alveolar pressure. Elastin in alveoli acts as an inward ‘collapsing’ force, i.e. elastic recoil. + Opposing elastic recoil of ribs acts as an outward expanding force. = Balance of forces results in a sub-atmospheric intrapleural pressure.

Answer 10

In quiet breathing, intrapleural pressure is always sub-atmospheric. Elastic retraction enables alveolar pressure to go above atmospheric pressure. [see notes for answer]

Answer 11

The forces contributing to elastic recoil is the elastin fibres, matrix elements within the lung parenchyma, surface tension and the air-liquid interface of the alveoli.

Answer 12

Is the measurement of the amount of work/effort you have to put in to breathe and expand the lung. Compliance = change in volume / change in pressure Lung with high compliance is easily distended. Lung with low compliance is difficult to distend. Static compliance is measured under conditions of no gas flow. Compliance varies with lung diseases. Idiopathic = diseases/conditions with unknown causes. Pulmonary compliance/elastic recoil is produced by elastin connective fibres and alveolar surface tension.

Answer 13

Molecules at the surface experience fewer favourable interactions than those in the bulk of the solution because the surface molecules can only interact with other molecules in 2 dimensions where as those in the bulk interact in 3 dimensions. This gives an energy cost to forming more surface with a set amount of material. Surface free energy (SFE) is the excess energy at the surface of a material compared to its bulk, arising from the imbalance of molecular forces at the surface. The relationship between SFE and surface tension is essentially equivalent as surface tension is the force per unit of length and surface free energy is the energy per unit of area. The high water/air tension explains why rain falls as drops and not sheets.

Answer 14

* Resists stretch (greater surface tension, less compliance thus higher elastance). * Tends to become smaller. * Tends to recoil after stretch -> contributes to elastic recoil pressure.

Answer 15

 Lung requires greater trans-pulmonary pressure to inflate with air in order to overcome surface tension and elastic recoil effect.  Inflating with liquid overcomes recoil effect by dissipating surface tension.

Answer 16

Small diameter bubbles have higher surface tension than large diameter ones. ↓ Variation in alveolar size/volume would cause small alveoli to collapse into larger ones. Pressure in bubble = 2 x surface tension / radius of bubble OR P = 2T / r

Answer 17

Pulmonary surfactant stabilises alveolar structure by reducing surface tension.  Surfactant reduces surface tension by decreasing density of water molecules at the air-water interface. Because the hydrophobic tail pulls the surfactant molecule upward the resultant vector in minimal.  Composed of Dipalmitoyl phosphatidyl choline (DPPC) packaged around surfactant proteins.  Secreted by type II alveolar epithelial cells.  Reduces surface tension in alveoli.  As r falls, surfactant molecules crowded together surface tension reduces and smaller alveolus stabilised.  Alveoli also stabilised by mechanical interactions between neighbouring alveoli prevent alveoli collapse.  Loss of surfactant causes alveolar collapse.

Answer 18

Elastance is the reciprocal of compliance, they are inversely related i.e. high compliance means low elastance and vice versa.

Answer 19

Dynamic Mechanical properties affecting flow of air into and out of lungs as volume changes with time. - Resistance - Flow - Turbulence

Answer 20

Resistance and Flow. In a normal airway 90% of resistance to flow is in the upper airway. The smallest tubes have the greatest airway resistance but there are loads of them so the cumulative resistance is actually lower. To calculate airway resistance we rearrange Poiseuille’s Law for resistance: i.e. Flow = change in pressure X [pi X radius^4 / 8 X the viscosity X tube length] Becomes: Flow = change in pressure /( 8 X the viscosity X tube length / pi X radius^4)

Answer 21

* Lung volume and branching * Bronchiolar smooth muscle tone * Density and viscosity of gases  Affected by altitude  Consideration in artificial environments such as space and deep sea  Laminar flow is a function of gas viscosity but turbulent flow depends on gas density

Answer 22

Lines the upper airway, alterations in tone alter the radius. ‘Tube’ radius decreases by muscular contraction. ‘Tube’ radius increased by muscular relaxation. This plays a major role in ventilation-perfusion matching and lung diseases related to resistance such as asthma.

Answer 23

[see notes for answer]

Answer 24

Allergic inflammation of the airways. → Bronchial smooth muscle thickening. ↘ ↗ Hyper-activity of airway smooth muscle contraction. Connective gas flow in the lungs is much less efficient. Gas flow slows to the molecular diffusion rate in the upper airway resulting in poor gas exchange in the respiratory acinus. Gas fails to penetrate to distal regions of the respiratory zone causing alveolar pCO2 to rise. Lung ceases to oxygenate Hb efficiently due to the reversal of proper alveolar Bohr and Haldane effects. Measurement of airway resistance by whole body plethysmography. R = (Pmouth – Palveolus) / flow

Answer 25

During inhalation airway resistance falls as gas flow and lung volume increase.  As lungs expand airways are also physically widened.  Dynamic lowering of resistance during lung expansion. During exhalation, the resistance of the upper airway helps to keep airway pressure high to maximise gas movement out of alveoli.

Answer 26

[see notes for answer]

Answer 27

- To overcome elastic and non-elastic resistances - Work = force x resistance, = pressure x volume

Answer 28

- Breathing movements are not spontaneous (unlike the cardiomyocyte). - Skeletal muscle which control breathing require neural input. - Neural input can be involuntary (tidal breathing) and voluntary (IRV, ERV, breathing frequency). - Chemo-receptive inputs monitor plasma and cerebral spinal fluid composition to maintain ventilating homeostasis (e.g. override voluntary breathing control).

Answer 29

Located in the brain stem; pons and medulla. Respiratory control centres in the brain; 2 centres 1) Pons respiratory centres - Pneumonic centre - Apneustic centre 2) Medullary respiratory centre - Pre-Botzinger complex - Dorsal respiratory group (DRG) - Ventral respiratory group (VRG)

Answer 30

* Inspiratory control * Located within the nucleus tractus solitaris and is dorsal to the VRG * Site of sensory information input * Site of central chemoreceptor input * Has some promoter neurons

Answer 31

* Spans 3 regions within the medulla 1) Rostral 2) Intermediate 3) Caudal  Rostral; expiration control (Botzinger complex).  Intermediate; inspiration control mediated through Pre-Botzinger complex – thought to be the site of Respiratory Pattern Generator.  Caudal; expiration control.

Answer 32

Hypoglossal nerve, laryngeal nerve and carotid sinus nerve = peripheral chemoreceptor feedback. Vagus nerve = breathing frequency and volume. Intercostal nerve = respiratory muscles. Phrenic nerve = diaphragm inspiration control.

Answer 33

- Diaphragm  Phrenic nerves, C3-5  Flattens on contraction  Moves 1cm in quiet breathing can move up to 10cm  Major inspiration muscle - External intercostals  Intercostal nerves at ‘rib level’ - Accessory muscles  Sternocleidomastoid, scalenus and others  Chest expands, intrapleural pressure falls

Answer 34

Mainly passive during quiet breathing (elastic recoil pressure is sufficient). - Forced expiration  Abdominal wall; transverse abdominals and rectus abdominus – push up against diaphragm.  Internal intercostals Cranial motoneurons are important for opening/closing glottis, affecting upper airway diameter, flaring nostrils etc. motoneurons controlling direct muscles of inspiration and expiration are therefore not the only ones active during breathing.

Answer 35

A network of interneurons that produce a predictable and repetitive motor pattern. In the case of breathing, inspiratory neurons must be activated before expiratory neurons.

Answer 36

- Always active even in the absence of conscious input (endogenous cyclical oscillation). - Transmit in an orderly sequence to respiratory muscles. - Respond to inputs from other parts of the brain (e.g. limbic system – emotions) as well as sensory afferents (e.g. pulmonary stretch receptors, peripheral chemoreceptors).

Answer 37

1) Inspiration 2) Post-inspiration 3) Expiration

Answer 38

1) Pre-inspiration 2) Early-inspiration 3) Inspiration 4) Late-inspiration 5) Early-expiration 6) Expiration

Answer 39

o Pre-inspiration neurons inhibit expiratory neural circuit. Effect; expiratory muscles relax. o Early-inspiration neurons inhibit the output from the entire RRG. Effect; refractory period, no breathing movements. o Inspiratory neurons ramp fire, as frequency increases more inspiratory neurons are contributing. Activates motoneuron circuit to inspiratory muscles and inhibit expiration and pre-inspiration neural circuits. Effect; inspiratory muscles contract as intensity of inspiratory firing increases, expiratory muscles ae relaxed. o Late-inspiratory neurons feedback to suppress inspiratory neuronal firing when at peak intensity. May involve stretch receptor input (from the vagus nerve). Effect; inspiratory muscles relax and lung begins to deflate due to elastic recoil. o Early-expiration neurons repress all inspiratory and expiratory neuronal firing. Creates refractory period at peak inhalation. Effect; inspiratory muscles relax and lung begins to deflate by elastic recoil. o Expiratory neurons ramp fire, activate motoneuron circuit to expiratory muscles. Major point of conscious input into breathing (e.g. during exercise). Effect; expiratory muscles contract as expiratory firing intensity increases, inspiratory muscles are relaxed.

Answer 40

* Normal -> burst firing of phrenic nerve causes diaphragm contraction and inhalation. * Increased tidal volume (VT) -> increased action potentials per burst gives stronger diaphragm contraction and deeper breathing. * Increased ventilation volume (VE) -> increased burst per minute gives increased breathing frequency. When combined with increased action potentials per burst (increased VT) then VE increases.

Answer 41

1) Central chemoreceptors – monitor pCO2 in cerebral spinal fluid (CSF). 2) Peripheral chemoreceptors – monitor pO2 and pCO2 and pH in blood and mixed lung gases. - Carotid body (blood) - Neuroepithelial bodies (airway) 3) Other receptor inputs  Stretch receptors Hering-Breuer reflex. Inhibition of lung over-inflation (>50% resting tidal). Increased breathing frequency following rapid lung deflation.  Allergens and Irritant receptors Located along the airway – feed into vagus. Cough, sneeze and bronchoconstriction reflex.

Answer 42

* Surface of the medulla * 80% contribution to normal control of breathing * Primarily detects pH changes caused by increase pACO2 in the CSF * Slow response time (minutes) * Linear response mode * Can be altered by training, is adaptive

Answer 43

* Found in arterial vasculature and airway * 20% contribution to normal control of breathing * Primarily detects decreased pAO2 in blood and airway, less responsive to increased pACO2 and decreased pH * Fast response time (seconds) * Non-linear response mode * Cannot be altered by training, is not adaptive

Answer 44

o Control system for normal breathing. o Directly responsive to CO2 driven pH changes in cerebral spinal fluid. o Response to changing alveolar pCO2 (pACO2) - Very sensitive to small changes in pACO2 - Hypoxia makes the response steeper (bigger change in VE per pACO2) - Hypoxia may bring central chemoreceptor cells closer to firing threshold o Adapt to sustained changes in pACO2 over several days, relevant to disease, high altitude, free diving, drug action. o Shallow water blackout; 1) Hyper ventilation drives pACO2 down. 2) O2 consumed during breath-hold dive. 3) Low central chemoreceptor sensitivity (caused by breath-hold training) fails to trigger breathing response in time to prevent severe hypoxaemia. 4) Loss of consciousness and drowning.

Answer 45

o Carotid body – carotid sinus. Aortic body – aortic arch. o Primary response to hypoxia, also respond to hypercapnia (increased pACO2) and acidosis (decreased pH). 1) Response to hypoxia is not linear, increases dramatically below pAO2 = 60 mmHg. 2) Response is driven by low partial pressure of O2 and not O2 concentration or HbO2 saturation. Does not occur with anaemia. 3) Hypercapnia or acidosis raises the sensitivity of chemoreceptor to pAO2.

Answer 46

1) Hypoxia The cell might sense pO2 by three mechanisms. a) O2 dissociates from haem- containing protein near K+ channel. b) Low pO2, somehow elevates [cAMP]i. c) Low pO2 inhibits NADPH-oxidase in mitochondria, raising the ratio of reduced to oxidised glutathione. Hypercapnia Elevated pCO2 leads to an influx of CO2 into the cell and production of H+. Acidosis Low extracellular pH inhibits acid-extruding transporters (e.g. Na-H exchangers) and also promoted intracellular acids loading, leading to a buildup of H+ inside the cell. 2) These mechanisms reduce the open-probability of K+ channels. 3) Inhibition of K+ channels depolarises the cells. 4) Depolarisation open voltage-gated Ca2+ channels, causing increased Ca2+ entry and increased [Ca2+]i. 5) Elevated [Ca2+]I triggers the release of neurotransmitters. 6) Neurotransmitters (probably dopamine) bind to postsynaptic membrane of afferent nerve fibres, generating action potentials that are conducted along the axon of the glossopharyngeal nerve (CN 9) which leads to the medulla.

Answer 47

A person with an extremely high fever (approaching lethality), body metabolism increases 100% above normal. In comparison, metabolism of the body during a marathon may increase to 2000% above normal. Exercise; - Initially disrupts homeostasis. - Often requires prolonged coordination among most body systems such as the muscular, skeletal, nervous, circulatory, respiratory, urinary, skin and endocrine.

Answer 48

* Heart = rest – 70 bpm, maximal exercise – 200 bpm. * Stroke volume = rest - ~70 ml, maximal exercise - ~130 ml. * Cardiac output = rest – 5 litres/min, maximal exercise – 25 litres/min. * Systolic pressure = rest – 120 mmHg, maximal exercise – 180 mmHg. * Diastolic pressure = rest – 80 mmHg, maximal exercise – 70 mmHg.

Answer 49

During exercise, cardiac output can increase to 20-25 l/min (~40 l/min in trained athletes during heavy endurance type exercise). Cardiac output increases in proportion to work load.

Answer 50

Control of heart rate is coordinated by the cardiovascular control centre in the brain stem. The immediate response to exercise; heart rate increases to deliver more oxygenated blood to the exercising muscles. Heart rate increases in proportion to work load, long-term adaptation to a regular exercise programme = increasing strength and efficiency. Max heart rate = 220 – age.

Answer 51

- Intrinsic; muscular contractions compress veins + venoconstriction. - Extrinsic ; sympathetic stimulation + adrenaline. [see notes for answer]

Answer 52

At rest (75 bpm); systole = 300 msec, diastole = 500 msec. At 180 bpm; diastole = ~125 msec.

Answer 53

Working muscles change the local chemical environment:  Local pO2 falls  Local pCO2 increases  Local [H+] rises (pH falls)  Muscle temperature rises All of the above lead to metabolic hyperaemia (localised vasodilation). Local controls override generalised sympathetic vasoconstriction e.g. blood flow to skeletal muscles in legs cf. arms during cycling. Effects are reinforced by the vasodilatory effects of adrenaline.

Answer 54

They are located in all arteriolar smooth muscle except in the brain. Chemical mediator Norepinephrine from sympathetic fibres and the adrenal medulla. Epinephrine from the adrenal medulla (but has less affinity for this receptor). Effect: Vasoconstriction.

Answer 55

Located in arteriolar smooth muscle in the heart and skeletal muscles. Chemical mediator Epinephrine from the adrenal medulla (has a greater affinity for this receptor than alpha1). Effect: Vasodilation

Answer 56

Cardiac muscle Increased metabolic activity of cardiac muscle cells (increased oxygen need) ↓ Increased adenosine. ↓ Vasodilation of coronary vessels. ↓ Increased blood flow to cardiac muscle cells. ↓ Increased oxygen available to meet increased oxygen need.

Answer 57

 Blood pressure is proportional to total peripheral resistance.  To meet the metabolic demands of the skeletal muscle there is a large drop in total peripheral resistance brought about by the vasodilation of the arterioles supplying the working muscles (40-50% of total body weight).  Diastolic blood pressure drops due to decreased total peripheral resistance.  Systolic blood pressure is increased due to the increased cardiac output.  The overall effect is a marginal increase in mean arterial blood pressure.

Answer 58

[see notes for answer]

Answer 59

o Heart rate = increases Occurs as a result of increased sympathetic and decreased parasympathetic activity to the SA node. o Venous return = increases Occurs as result of sympathetically induced venous vasoconstriction and increased activity of the skeletal muscle pump and respiratory pump. o Stroke volume = increases Occurs both as a result of increased venous return by means of the Frank-Starling mechanism (unless diastolic filling time is significantly reduced by high heart rate) and as a result of a sympathetically induced increase in myocardial contractility. o Cardiac output = increases Occurs as result of increases in both heart rate and stroke volume.

Answer 60

o Blood flow to active skeletal muscles and heart muscle = increases Occurs as a result of locally controlled arteriolar vasodilation, which is reinforced by the vasodilatory effects of epinephrine and overpowers the weaker sympathetic vasoconstrictor effect o Blood flow to the brain = unchanged Occurs because sympathetic stimulation has no effect on brain arterioles; local control mechanisms maintain constant cerebral blood flow whatever the circumstances. o Blood flow to the skin = increases Occurs because the hypothalamic temperature control centre induces vasodilation of skin arterioles; increased skin blood flow brings heat produced by exercising muscles to the body surface where the heat can be lost to external environment.

Answer 61

o Blood flow to the digestive system, kidneys, and other organs = decreases Occurs as result of generalised sympathetically induced arteriolar vasoconstriction. o Total peripheral resistance = decreases Occurs because resistance in the skeletal muscles, heart, and skin decreases to a greater extent than resistance in the other organs increases. o Mean arterial blood pressure = increases moderately Occurs because cardiac output increases more than total peripheral resistance decreases.

Answer 62

[see notes for answer]

Answer 63

[see notes for answer]

Answer 64

 In severe exercise, lactic acid production.  H+ stimulates peripheral chemoreceptors.  Ventilation excessively stimulated.  CO2 excessively blown off – VCO2 exceeds VO2.  Respiratory exchange ratio exceeds 1 (in severe exercise, RER does not reflect the predominant metabolic substrate.

Answer 65

Exercise profoundly increases ventilation but the mechanisms involved remain unclear. Alveolar ventilation can increase up to 20 fold during heavy exercise. Mechanisms remain speculative as: - Arterial pO2 does not decrease (may actually increase) - Arterial pCO2 des not increase (may actually decrease) - During mid-moderate exercise [H+] plasma does not increase (H+ - generating CO2 is held constant) - During heavy exercise elevation of H+ from lactate (lactic acid) is not enough to account for the large increase in ventilation Slight decline in arterial pCO2 during heavy exercise + ventilation increases abruptly at the onset of exercise (within seconds), long before changes in arterial blood gases can influence the respiratory centre.

Answer 66

1) Reflexes originating from body movements. 2) Increase in body temperature. 3) Adrenaline release. 4) Impulses from the cerebral cortex. None of these factors (or combinations) are fully satisfactory in explaining the abrupt and profound effect has on ventilation.

Answer 67

Predictor of a person’s work capacity is determination of maximal O2 consumption (VO2 max).  Bicycle ergometer or treadmill  Workload is progressively increased until exhaustion  Expired air is collected during the last minutes (when O2 consumption is at a maximum)  %O2 and %CO2 + volume of air measured Regular exercise can improve VO2 max; heart and respiratory system become more efficient, exercised muscles become better equipped to use O2 once it is delivered. VO2 max is measured in l/min, then converted to ml O2/kg body weight/min to allow comparison between individuals. Individuals can be classified as being low, fair, average, good or excellent in aerobic capacity for their age group. Exercise physiologists use VO2 max measurements to prescribe or adjust training programmes to help individuals achieve their optimal level or aerobic conditioning.

Answer 68

The work of breathing requires ~3% of total energy expenditure. During strenuous exercise this may increase 25 fold. However, total energy expenditure increases 15 to 20 fold during heavy exercise, the energy used for increased ventilation still represents ~5% of total energy expended. During exercise the surface area for exchange can be increased to enhance the rate of gas transfer. Increased cardiac output -> increased pulmonary blood pressure open previously closed capillaries. Alveolar membranes are stretched due to larger tidal volume (deeper breathing). VE = TV x Rf

Answer 69

[see notes for answer]

Answer 70

o CO2 release from red cell / O2 uptake by alveolus 1) O2 dissolves into plasma and red cells along the partial pressure gradient. 2) High affinity Hb for O2 reverses Hb carbamation and protonation raising availability of high affinity Hb (Bohr effect). 3) CO2 diffuses into alveolus along pressure gradient. High PO2 decreases CO2 affinity for Hb (Haldane effect). 4) Movement of CO2 out of red cells increases HCO3- uptake, Cl- moves out. 5) Proton release from Hb and an increased HCO3- drive carbonic anhydrase reaction in reverse, maintaining outward CO2 gradient and lowering plasma bicarbonate.

Block 4 - Respiratory Flashcards

(94 cards)