(Integrated Physiology Ii; Unit 4) Cardiovascular And Respiratory Physiology

Front 1

Describe the steps in excitation contraction coupling.

Back 1

- Ca2+ enters cell during depolarization and triggers release of Ca2+ from terminal cisternae

- Ca2+ binds to troponin-C inducing conformational change in troponin complex

- Myosin binds actin – cross bridge cycling occurs

- Ca2+ is sequestered by SR via SERCA pumps

- Ca2+ leaves troponin-C, myosin cannot bind actin

- Sarcomere returns to original relaxed length

Front 2

There are seven 'phases' that occur during the cardiac cycle. What are they?

Back 2

Atrial systole;

- Atria contract, topping up mostly filled ventricles

Isovolumetric contraction;

- Ventricles contract, but all valves are closed

Rapid ejection;

- Semilunar valves open, ventricles expel blood

Reduced ejection;

- Semilunar valves open, end of ventricular contraction

Isovolumetric relaxation;

- Ventricles relax, all valves remain closed

Rapid ventricular filling;

- AV valves open, blood begins to fill the ventricles

Diastasis;

- Ventricles fill slowly as venous pressure>ventricular pressure

Front 3

What are the functions of the lungs and respiratory tract?

Back 3

- Gas exchange of 02-C02

- Metabolism (ACE)

- Acid-Base balance

- Thermoregulation

- Immune defence

Front 4

What are the non-respiratory functions of the lung?

Back 4

Immune function and defence against infection;

- Mucociliary escalator

- Many lymph nodes

- lgA secretion

- Alveolar macrophages and neutrophils

Cardiovascular / Volume regulation;

- Conversion of angiotensin I to angiotensin Il via angiotensin converting enzyme (ACE)

- Inactivation of bradykinin, 5-HT (serotonin), prostaglandin

- Uptake of norepinephrine, histamine (by lung slice)

- Metabolism and release of arachadonic acid metabolites

- lipoxygenases >leukotrienes cyclooxygenases > prostaglandins/thromboxane A2

- Clotting — mast cells contain heparin

Front 5

What is 'Vital capacity'?

Back 5

- The maximum amount of air a person can expel from the lungs after a maximum inhalation. It is equal to the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume

- A normal adult has a vital capacity between 3 and 5 litres.

Front 6

Explain the conductive airways.

Back 6

- Airways consist of series of branching tubes

- Trachea to terminal bronchioles

- No gas exchange = Anatomic dead space

Front 7

Explain the respiratory zone.

Back 7

- Respiratory bronchioles to alveoli

- Where gas exchange occurs

- Functional unit distal to terminal bronchiole is called the acinus

Front 8

Explain the structure of the Trachea.

Back 8

- The trachea is composed of about 20 rings of tough cartilage. The back part of each ring is made of muscle and connective tissue. Moist, smooth tissue called mucosa lines the inside of the trachea. The trachea widens and lengthens slightly with each breath in, returning to its resting size with each breath out. Cilliated epithelium lines the trachea, with goblet cells amongst as well.

Front 9

Explain the structure of the bronchiole.

Back 9

- No longer contain cartilage, cilliated epithelium or goblet cells.

- Clara cells prevent collapsing

- Contains smooth muscle (can prevent air from exchanging from alveoli)

- Lots of lymph nodes

Front 10

Explain the structure of the Alveolar duct.

Back 10

- Alveoli on all sides

- Openings guarded by rings of smooth muscle, continuous with spiral smc

- Contraction allows redistribution of gas

- Calibre is much greater than respiratory bronchiole Alveolar sac

Front 11

Explain the structure of the alveolar sac.

Back 11

- Rotunda-like area at the end of the alveolar duct

- Alveoli around all its walls

Front 12

Explain the structure of Alveolus

Back 12

- Adjacent alveoli share the alveolar septum/wall Helps to protect against alveolar collapse (atelectasis)

- Pores of Kohn gaps" in the alveolar septa to enable more efficient movement of inspired air between alveoli

- These features add to the "interconnectedness' of the alveoli in the lung

- Thin part of alveolar wall allows for as exchange

- Thick part contains collagen and elastic fibres for structure

Front 13

How do the muscles of the lungs work against the physical impedance of the respiratory system?

Back 13

- Elastic resistance of lung tissue and chest wall (compliance)

- Resistance from surface forces at alveolar gas- liquid interface (surface tension)

- Frictional resistance to gas flow through the airways

- Frictional resistance from deformation of thoracic tissues (viscoelastic tissue resistance)

- Inertia associated with movement of gas and tissue

Front 14

What muscles work for inspiration?

Back 14

- As the diaphragm contracts, it increases the thoracic volume which lowers the pressure, and in turn air moves in passively

- External intercostal muscles and Scalene muscles also aid in this

Front 15

What muscles work for expiration?

Back 15

- Resting breathing is passive

- During exercise, abdominal muscles and internal intercostal muscles

Front 16

What is elastic recoil?

Back 16

- Pressure surrounding lung in chest is less than atmospheric due to "elastic recoil"

- Elastin and collagen fibres in alveolar walls and around airways and blood vessels

- Lung returns to its resting volume after distension

- Chest wall is under tension too Intercostal muscles rib cage 'spring out"

-Iintrapleural pressure is subatmospheric

Front 17

What is 'Lung compliance'?

Back 17

- Volume change per unit pressure change (the slope of the pressure volume curve)

- Dynamic and static compliance

Front 18

Explain the compliance of the lung.

Back 18

- As expanding pressure increases lung becomes stiffer and less compliant — flatter slope of curve (imagine blowing up a balloon) - Compliance depends on size — therefore we sometimes measure specific compliance

- Reduced compliance caused by pulmonary fibrosis, Alveolar oedema, atelectasis,

increased pulmonary venous pressure

- Increased compliance — pulmonary emphysema, normal ageing process

Front 19

What is surface tension?

Back 19

- The force acting n the surface of a liquid (unit = dynes)

- Laplace's Law: Pressure = 4(surface tension)/radius

- The effect of surface tension forces on the "lumen" of the soap bubble mean that the smaller the bubble the greater pressure there is within the bubble so it is more likely to burst

Front 20

What is 'Pulmonary surfactant'?

Back 20

- Increases compliance of the lung and reduces work of expanding it with each breath

- Promotes stability of each alveoli (soap bubbles analogy)

- Keeps alveoli dry

- Phospholipid containing dipalmitoyl phosphatidylcholine (DPPC) Secreted from type Il alveolar cells (type Il pneumocytes)

- Structure of DPPC: hydrophobic at one end and hydrophillic at the other

- Alignment at the surface causing intermolecular repulsive forces which oppose the normal attractive forces between the liquid molecules that are responsible for surface tension

- When surfactant is compressed it reduces surface tension further — molecules of DPPC are closer together and repel each other more

Front 21

What is 'Infant respiratory distress syndrome'?

Back 21

- Effect of lack of surfactant

- Stiff lungs with low compliance

- Atelectasis

- Alveoli filled with transudate

-Treat with synthetic surfactant

Front 22

How does regional differences effect ventilation?

Back 22

- Lower regions of lung ventilate better than upper regions

- Due to gravity acting on lungs to reduce intrapleural pressure at lung base

- Alveoli are smaller at the bottom of the lung

- Show greater change in volume during inflation - More compliant

Front 23

What is airway resistance?

Back 23

Airway resistance = pressure difference between alveoli and mouth divided by flow rate. Measure mouth pressure with manometer alveolar pressure with body plethysmograph

Front 24

What factors determine airway resistance?

Back 24

- Lung volume dynamic compression of airways

- Contraction of bronchial smooth muscle

- Density and viscosity

- Tissue resistance

- Remember that the upper respiratory tract is a very important site of resistance to airflow to the lung!

- Total resistance (pulmonary resistance) = airway + tissue resistance

Front 25

What is Fick's law?

Back 25

- Rate of transfer of gas through a sheet of tissue is proportional to the tissue area and the difference in partial pressure between the two sides, and inversely proportional to the tissue thickness

Front 26

What factors affect diffusion (Fick)?

Back 26

- Thickness of respiratory membrane

- Surface area of membrane (300 million "bubbles")

- Diffusion coefficients of gases

- Partial pressure differences of gas between two sides of membrane

- Diffusion capacity of respiratory membrane, the volume of gas that will diffuse through the membrane for each minute for a partial pressure difference of 1 mmHg

Front 27

What happens during exercise?

Back 27

- Pulmonary blood flow increases

- opening up of dominant capillaries

- better matching of ventilation and perfusion

Front 28

Describe 'Bronchial circulation'.

Back 28

Bronchial circulation

- Low volume

- High pressure input from aorta

- Arterial blood to lungs to supply metabolic needs of tissues of bronchial tree

- Blood is then returned to the left side of the heart

- i.e. small right-to-left shunt •Outer and inner blood-vascular plexuses — functional importance- peribronchial sheath

Front 29

Describe 'Pulmonary circulation'.

Back 29

- Large volume system

- Low pressure input from pulmonary trunk, carries venous blood to the lungs

Front 30

Describe 'Pulmonary blood flow'.

Back 30

- Blood to pulmonary capillaries is from right heart — deoxygenated

- Pulmonary vein — oxygenated blood contaminated with blood from bronchial circulation (anatomical shunt)

- Better perfusion at base of lung (similar to ventilation)

- Due to gravity (hydrostatic pressure)

- Dependent on animal size and posture and position of lung in relation to heart

Front 31

what factors effect perfusion?

Back 31

Alveolar oxygen: when 02 decreases below about 73mmHg blood vessels constrict. Opposite to systemic circulation Effect — to distribute blood flow to where it is most effective

- Exercise: increasing number of open capillaries distending all capillaries and increasing blood flow increasing pulmonary arterial pressure

- Left-sided heart failure > Blood collects in left atrium > increased left atrial pressure increased pulmonary arterial pressure > increased load on right heart > pulmonary edema (swelling) is likely

Front 32

What is Ventilation/Perfusion (V/Q) mismatch?

Back 32

- Presence of a degree of shunt and a degree of dead space in the same lung

- Component of most causes of respiratory failure

- Most common cause of hypoxaemia

Front 33

What is 'Alveolar dead space'?

Back 33

- Well ventilated with almost no blood flow

- V/Q = infinity

- (Imagine there is a blockage in the capillary)

- 02 level in alveolar = same as air

Front 34

What is 'Shunt'?

Back 34

- Some areas normal blood flow but little or no ventilation

- V/Q = 0

- (imagine blockage at entrance of alveolar, preventing any entrance of gas)

- 02 leveling alveolar = that of delivered blood

Front 35

Describe diffusion of oxygen from peripheral capillaries into tissue fluid.

Back 35

- Systemic arterial blood 95mmHg

- Interstitial fluid 40mmHg

- Very large pressure difference rapid diffusion of 02 into tissue

- P02 of blood leaving the capillaries drops to almost 40mmHg

- 02 readily diffuses out of capillaries and into tissue fluid

Front 36

What is 'Systolic arterial pressure'?

Back 36

- Peak pressure in the arteries when the LV isejecting blood during ventricular systole

Front 37

What is 'Diastolic arterial pressure'?

Back 37

- The residual pressure in the arteries when theLV is filling during ventricular diastole

Front 38

What is the equation to find cardiac output?

Back 38

CO = HR * SV

(HR = Heart Rate)

(SV = Volume of blood pumped out each pump)

Front 39

What is the equation to find mean arterial pressure?

Back 39

MAP = CO * TPR

(CO = cardiac output)

(TPR = Total peripheral resistance)

Front 40

What does effective regulation of MAP require?

Back 40

- Sensors

- Integrating system

- Effectors

Front 41

Which sensors regulate MAP?

Back 41

Baroreceptors;

- Non-encapsulated nerve endings in adventitia ofarteriesaortic arch and carotid sinus

- Central axons terminate in nucleus tractus solitarius

- Serve as mechanoreceptorsincreased firing in response to distension

Front 42

How does Haemoglobin transport O2?

Back 42

- O2 binds loosely and reversibly with the heme portion of Hb

- HighPO2 (eg pulmonary capillaries) O2 binds to Hb

- LowPO2 (eg peripheral capillaries) O2 is released from Hb

Front 43

How does blood PH effect oxygen-hemoglobin dissociation?

Back 43

- As PH drops and becomes more acidic, haemoglobin will have a lower affinity for oxygen and dissociate more

Front 44

What is 'Carbaminohaemoglobin'

Back 44

- CO2 reacts directly with amine radicals of Hb to formCO2Hb

- Reversible reaction with loose bond, so CO2 is easilyreleased into alveoli

- About 1.5ml CO2/100ml blood carried this way

- but the reaction is slow so only 23% CO2 transportedthis way

Front 45

What is the 'Haldane effect'?

Back 45

- Binding of O2 with Hb tends to displace CO2 from the blood

- When O2 binds Hb in the lungs the Hb becomes a stronger acid

- Causes displacement of CO2 from blood to alveoli

- less tendency to form carbaminohaemoglobin

- excess of H+ is released which bind to HCO3 leading to CO2 release

Front 46

What do the Central chemoreceptors do?

Back 46

- Respond to change in chemical composition of the bloodVentral surface of medulla near exit of 9th and 10th nerves

Respond to changes in H+;

- increase stimulates ventilation

decrease inhibits ventilation

Front 47

What do the peripheral chemoreceptors do?

Back 47

- Carotid bodies and Aortic bodies

- Arterial chemoreceptors are excited by increase in arterialPCO2 or H+OR reduction in arterialPO2

- They induce a reflex increase in breathing

Front 48

What lung receptors are there?

Back 48

Pulmonary stretch receptors;

- “slowly adapting pulmonarystretch receptors”

- “Hering-Breuer inflation reflex”

Irritant receptors;

- “rapidly adapting pulmonary stretch receptors”

J receptors;

- “juxtacapillary”, believed to be in alveolar walls close to capillaries

Bronchial C-fibres

Front 49

What parasympathetic neuronal control of airway diameter is there?

Back 49

Parasympathetic – major importance in the control ofbronchomotor tone;

- Can completely obliterate lumina of smallairways

- Afferent and efferent fibres via vagus nerve

- Efferent ganglia in walls of small bronchi; ACh release acts on M3 receptors, causing contraction of bronchial smooth muscle

- Some degree of resting tone normally present

Front 50

What sympathetic neuronal control of airway diameter is there?

Back 50

Sympathetic – not yet proven to be of majorimportance (in humans); evidence for direct sympathetic innervationof airway smooth muscle

NANC – efferent fibres via vagus;

- Neurotransmitter vasoactive intestinalpeptide (VIP)

- Promotes production of NO leading toairway SMC relaxation

- Also a bronchoconstrictor part to theNANC system)

Front 51

What hormonal control of the airway diameter is there?

Back 51

Presence of manyβ2 adrenergic receptors;

- Highly sensitive to circulating adrenaline acting viacomplex 2nd messenger pathways

- Probably of greatest importance during exerciseand sympathetic“stress”response

Cytokine production by inflammatory cells can lead torelease of broncho-active mediators;

- Mostly bronchoconstriction(histamine, prostaglandin D2, F2a etc.)

- (prostaglandin E2 and prostacyclin are bronchodilators)

Front 52

How is CVS and respiration integrated?

Back 52

Role of Peripheral Arterial Chemoreceptors during heartfailure

- Firing causes a pressor reflex response (increase BP) through actionon vascular smooth muscle

- Enables CVS to transport more O2 and remove excess CO2

These chemoreceptors also respond directly to a fall in AP below80mmHg:

Fall in AP > reduced blood flow > reduced O2 availability > increased discharge rate > reflex rise in AP

Baroreceptors;

- Rise in BP can cause hypoventilation and apnoea

- Fall in BP can cause hyperventilation

Front 53

Describe the respiratory reflex response to haemorrhage.

Back 53

Front 54

How is lung capacity affected by training?

Back 54

Respiratory system not normally limiting factor in O2 deliveryHowever;

- After training, diffusing capacity of the lung increases(even untrained 3-4x due to capillaries opening and better V/Qduring exercise)

- Oxygen consumption (VO2Max) increases(10% short training regime, up to 50% long term training)