Week 8

Question 1

Vasoconstriction and vasodilation of arterioles alter resistance to flow

Answer 1

Vasodilation- increases flow
Normal tone-all arterioles slightly constricted at rest
Vasoconstriction- decreases flow
Controlled by:
-endothelial factors
-local mechanisms
-central neural mechanisms
-hormonal mechanisms

Question 2

Constriction of arterioles

Answer 2

Constriction of arterioles to one organ decreases flow to that organ. Eg skin in cold conditions
Constriction of arterioles to multiple organs can increase TPR and therefore increase ABP
Useful for maintaining ABP during standing or haemorrhage

Question 3

Endothelial control

Answer 3

Dilation:
-NO synthesised continuously by nitric oxide synthase converting L arginine. Leads to fall in Ca2+ levels in SMC causing vasodilation, helps to increase coronary blood flow in exercise when cardiac activity and metabolism are increased
-prostaglandins PGE, PGI2, EDHF(endothelium derived Hyperpolarisation factor)
-lots of triggers: circulating hormones, paracrine hormones, shear stress due to increased blood flow and local hypoxia
-in coronary artery disease NO synthesis reduced, this limits increases in coronary flow in exercise and limits cardiovascular ability
Constriction:
-endothelins: Ang-II, trauma, acts via intracellular calcium release, increases levels leads to contraction. Some forms hypertension can be treated with endothelin blockers
-thromboxane
-PGF

Question 4

Local factors metabolic mechanisms

Answer 4

Adenosine, K+, CO2, H+- vasodilator
Lactate
Vasodilation, increased blood flow
Resistance vessels close by are very sensitive to these byproducts and vasodilation of arterioles occur locally in tissue. Increase oxygen and nutrient supply to tissue either by action on vascular smooth muscle or endothelium

Question 5

Active or functional hyperaemia

Answer 5

An increase in flow due to an increase in the metabolic activity
Proportional to need

Question 6

Reactive hyperaemia

Answer 6

Transient increase in flow seen after period of no flow usually due to arterial occlusion
Eg seen in muscles after isotonic contraction such as weightlifting. Thought to be due to build up of metabolites during occlusion which are then washed out in hyperaemia causing vasodilation

Question 7

Central neural mechanisms

Answer 7

Most vascular smooth muscle has tonic vasomotor tone due to ongoing sympathetic nerve activity SNA
- decreased SNA= vasodilation
-normal tone (some degree of vasoconstriction)
-increased SNA= vasoconstriction
All vessels including skeletal muscle a1 adrenoceptors
Skeletal muscle also has B2 adrenoceptors
when NA released from increased SNA binds to a1 causing vasoconstriction but binds weakly to B2 receptor
In response to increased sympathetic nerve activity the a1 receptor effect predominates in skeletal muscle
Little or no parasympathetic innervation (only in exocrine glands of head and genitalia)

Question 8

Hormonal mechanisms adrenaline

Answer 8

What if plasma adrenaline increases
The presence of a and B receptors on arterioles indicates that circulating adrenaline will also be capable of changing radius of arterioles
Although primary effect of circulating adrenaline is increasing HR and contractility it tends to cause vasodilation as it has a high affinity for B2 receptors
However as plasma adrenaline increases the dominant receptor response changes to a receptor causing vasoconstriction
In response to circulating adrenaline the B2 receptor effect predominates in skeletal muscle (fight or flight)

Question 9

Hormonal mechanisms

Answer 9

ADH (vasopressin)— vasoconstriction V1 receptor
Angiotensin II— AT1 receptor causing vasoconstriction

Question 10

Local factors

Answer 10

Myogenic mechanisms: reflex vasoconstriction in response to increase intravascular pressure, when lumen suddenly expands smooth muscle responds by contracting to restore original diameter
Autoregulation: metabolic and myogenic. Resistance vessels dilate at low pressure to maintain optimal flow and constrict at high pressure.
- cerebral vessels autoregulate between ~60-150mmHg
- kidney vessels autoregulate between ~80-200mmHg

Question 11

A-vO2 difference

Answer 11

Depends on oxygen demand in tissue
Large a-vO2 difference (eg in heart) high oxygen consumption
Smaller a-vO2 difference (eg kidney and skin) consume less oxygen

Question 12

Vascular anatomy

Answer 12

Left coronary and right coronary artery
Lines epicardial surface
Acts as distribution vessels, branches into myocardium acts as resistance vessels
Ventricles have higher supply than atria, LV higher blood supply
Coronary arteries derived from aorta just distal to aortic valve
Coronary veins adjacent to arteries, venous drainage into coronary sinus which empties into right atrium
Some drained via thesbian veins, small drop in O2 content in systemic blood

Question 13

Coronary arteries

Answer 13

Supplies the myocardium and must maintain continues flow for normal function (low capacity for anaerobic metabolism)
Receives ~5% CO at rest
Extracts almost maximum amount of O2 possible at rest
Very large a-Vo2 difference even at rest high oxygen consumption
In coronary circulation the regulation of flow is responsible for matching oxygen supply to metabolic demand
Any increased demand for O2 must be met by large flow increases
Large endothelial surface area for exchange, reduces diffusion distance will facilitate oxygen delivery to tissues. 1 capillary per myocyte

Question 14

Cardiac tissue myoglobin

Answer 14

Has 3.4g/l myoglobin
Can only bind 1 molecule oxygen much higher affinity than Hb
In capillaries coronary circulation Hb can handover oxygen to myoglobin inside cardiac muscle cells
This myoglobin transfers oxygen to next myoglobin molecule and so on, speeds up diffusion oxygen through muscle cell to mitochondria

Question 15

Control of coronary flow

Answer 15

Coronary arteries exhibit myogenic auto regulation in pressure range 50-150 mmHg
Any change in pressure met with change in resistance to maintain flow
Coronary flow reserve- difference between resting level of flow and maximum flow that could be obtained by dilating vessels, used as an indicator of the ability of flow to increase when heart is stressed, reduced in some cardiac conditions
Allows blood flow to increase 5 times above resting auto regulatory level when CO increased
Some sympathetic control but overridden by local control

Question 16

Metabolic/functional hyperaemia dominant form of regulation

Answer 16

An increase in metabolic activity fall in coronary blood flow or fall in myocardial PO2 release adenosine (breakdown product of ATP)
Adenosine is a vasodilator acts by reducing intracellular Ca2+ in vascular smooth muscle cells
Prostaglandins
Low O2, high CO2
NO
K+ (extracellular K+ levels also rise when cardiac work increases may contribute to initial increase in coronary perfusion but is unlikely to mediate sustained rises in coronary flow)
Vasodilation increases blood flow

Question 17

Flow interruption

Answer 17

Oxygen deficit myocardial hypoxia
Stenosis of left coronary artery- commonly occurs in large epicardial arteries, needs to exceed 60-70% reduction in diameter to have significant effect on flow
Coronary artery disease: such as atherosclerosis, also causes endothelial damage and dysfunction, prostacyclin, falls in NO
Cardiac tissue hypoxia—> angina—> stable angina (fixed stenosis, demand ischaemia, not normally life threatening). Unstable angina—> (thrombus) indicates danger of vessels becoming completely occluded, supply ischaemia. Interventions; balloon angioplasty, stent, coronary bypass graft surgery

Question 18

Left coronary flow

Answer 18

Most blood flows to the left myocardium during diastole (85%)
Aortic pressure (Pin) during diastole determines flow
Max during early diastole
At high HR diastole is shortened and reduces time for perfusion
Coronary perfusion pressure: aortic diastolic pressure- LVEDP

Question 19

Extravascular compression in left ventricular wall

Answer 19

Contracting myocytes collapse vessels
Arterial blood is forced back towards aorta
Reversal of blood flow through vessels supplying the left ventricular wall during systole (extra vascular compression)

Question 20

Must maintain totally secure O2 supply to brain tissue

Answer 20

Grey matter (receives 100ml/min/100g VO2 at rest~7ml O2/min/100g)- high oxidative metabolism, very sensitive to hypoxia
Low oxygen leads to: loss of consciousness>4 min leads to neuronal damage
Local flow alters according to activity (metabolic/functional hyperaemia)

Question 21

Structural adaptations

Answer 21

Circle of Willis: 2 internal carotid and 2 vertebral arteries, anastomose
Short arterioles, dense capillary network
Relatively high vascular resistance
Cerebral perfusion maintained if carotid artery obstructed

Question 22

High capillary density aids gas exchange

Answer 22

Large SA
Reduces diffusion distance
Brain capillary endothelial cell
Tight junctions: not leaky, prevents bulk flow and diffusion of water and ions that’s seen between capillary cells in systemic circulation
Cellular basis of blood-brain barrier

Question 23

Blood brain barrier

Answer 23

Lipophilic solutes (cerebral capillary permeable): such as O2, CO2, alcohol, nicotine, caffeine
Amino acids pass using transport proteins
Epithelial cells have 5-6x mitochondria as muscle epithelium
When K+ in interstitium increases due to neuronal activity K+ is pumped out by Na+/K+ ATPase regulates K+ concentrations
Cerebral capillaries form tight junctions (no bulk flow)
No vesicular transport
Protects neurones
Maintains environment

Question 24

Functional adaptations

Answer 24

High basal flow- high O2 extraction
Regulation of other organs safeguards cerebral circulation- peripheral vasoconstriction (except heart) can maintain arterial pressure therefore cerebral flow
Autoregulation well developed between 60-150mmHg
Resistance vessels dilate at low pressure to maintain optimal flow and constrict at high pressure
Below 60mmHG- mental confusion and syncope

Question 25

Cerebral vessels are very responsive to arterial CO

Answer 25

Hypercapnia (high PaCO2> 5KPa) induces vasodilation cerebral vessels Useful during asphyxia to maintain O2 delivery Endothelial NO and Fall in myocyte pH mediate vasodilation Small pial arteries dilate more than larger cerebral arteries in response to CO2 Hypocapnia (low PaCO2<5kPa) causes vasoconstriction will 1/2 cerebral flow Responsible for dizziness during hyperventilation

Question 26

Cerebral vessels are less responsive to levels of arterial O2

Answer 26

Hypoxia (low PaO2) Moderate hypoxia evokes little change in cerebral flow Severe hypoxia leads to vasodilation- adenosine, K+, NO so systemic hypoxia only has minor overall affect on cerebral flow. Will evoke hyperventilation through stimulation carotid chemoreceptors- fall in arterial CO2–cerebral vasoconstriction Systemic hypoxia evokes hyperventilation so hypoxic vasodilation often masked by hypocapnic vasoconstriction

Question 27

Neuronal activity-evoked functional hyperaemia

Answer 27

Factors important in coupling tissue metabolism to local flow: -neuronal activity increased potassium permeability membranes, increase interstitial K+ -adenosine (metabolic messenger) -neuronal nitric oxide -metabolites released from astrocytes during increased activity -CO2, increased levels can cause vasodilation Flow shifts with mental focus to keep net cerebral flow constant

Question 28

Is nervous control important in determining cerebral flow

Answer 28

Maximal sympathetic stimulation increases resistance by only 20-30% Baroreceptors have little influence on cerebral flow Sympathetic stimulation shifts autoregulatory curve to right: to protect brain from damaging effects elevated pressure, this will make individual more susceptible to reduced perfusion if BP falls below lower end of autoregulatory range Autonomic nerves have little effect on cerebral flow

Question 29

Vascular problems

Answer 29

Raised intracranial pressure ICP 3 intracranial constituents: tissue, blood, CSF ICP raised by: -intracranial bleeding -cerebral oedema -tumor Increased ICP: -collapses veins -decreased effective CPP -reduce blood flow Cerebral perfusion pressure: mean ABP-ICP (normally 0-10) Postural syncope if baroreflex/autonomic activity impaired eg ageing, neuropathy Transient ischaemic attack TIA Cerebrovascular accident (stroke) -ischaemic stroke occurs when there’s atherosclerosis or blood in extra cerebral artery -haemorrhagic stroke- weakened vessel wall ruptures causing bleeding in the brain

Question 30

Function cutaneous circulation

Answer 30

Provide skin with modest metabolic requirements Regulate body temperature Skin is major thermoregulator Receives ~10% CO Cutaneous blood flow can vary from 1-200 ml/min/100g

Question 31

Unique microvascular network

Answer 31

Most cutaneous blood volume is in venous plexus can contain up to 1.5L blood Capillary loops under epidermis and blood flows into venules Venous plexus- also receives blood directly from subcutaneous arteries through interconnecting vessels called arterio-venous anastomosis, in this way some blood flow can bypass capillaries in epidermis and flow straight into venous plexus Arterioles penetrate into dermis giving rise to capillaries AV anastomosis are particularly prominent feature in skin of nose, lips, ears, toes and fingertips

Question 32

Response to increased temperature

Answer 32

Arterioles dilate due to withdrawal sympathetic tone When temp increases decrease in SNS activity causes AV anastomosis to dilate and increases blood flow straight into venous plexus Nutritional flow through capillaries into epidermis still maintained Large area for heat exchange between blood, skin, environment AV anastomoses dont show functional hyperaemia or Autoregulation so their activity governed mainly by changes in sympathetic activity . They have thick muscular walls which are richly supplied by sympathetic nerve fibres acting on alpha adrenoceptors Removal of alpha adrenoceptors mediated sympathetic tone— dilation of cutaneous arterioles, dilations of AVAs— increase blood flow into venous plexus

Question 33

When temp rises hypothalamic stimulation of

Answer 33

Sympathetic (cholinergic) fibre innervating sweat glands Sweat contains enzyme that acts in tissue to release bradykinin Bradykinin is a polypeptide vasodilator acts locally in paracrine fashion to relax smooth muscle enhance vasodilation

Question 34

Increase temperature

Answer 34

Direct effect of temp on SAN ABP= CO x TPR Vasodilation of arterioles and AVAs Decrease TPR Decreased ABP Decrease baroreceptor afferent activity to CNS Decrease vagal activity to SAN Increase symp activity to SAN Increase HR 10beats/min/degree C Increase CO Increase ABP Inability to increase CO can lead to falls in BP being too great = syncope

Question 35

Responses to decreased temperature

Answer 35

Increase sympathetic activity to cutaneous vessels NA release Stimulation of a-adrenoceptors mediated sympathetic activity Constriction of arterioles Constriction of AVAs— decrease blood flow into venous plexus Blood diverted to interior vessels- lower resistance, minimised heat loss by keeping blood away from surface, diverted to deep veins lie beneath insulating fat

Question 36

Paradoxical cold vasodilation

Answer 36

With prolonged exposure to cold the vasoconstriction in cutaneous circulation changes to paradoxical cold vasodilation- skin red Thought to prevent cold weather injury to tissue Due to paralysis of noradrenergic transmission in response to cold and release vasodilators such as prostacyclin Redness of blood largely due to increase in affinity to Hb for O2, left shift in oxygen dissociation curve at colder temps

Question 37

Countercurrent exchange

Answer 37

Traps heat near trunk Warm blood from body core travels to peripheries in arteries Arterial blood transfers heat to cold blood returning in veins from periphery helps trap heat to body core Can occur in opposite direction if extremities exposed to heat

Question 38

Raynaud’s disease

Answer 38

Skin vessels over reactive Peripheral arterioles restrict excessively in response to cold Cold/emotional stimuli lead to vasoconstriction (ischaemic attacks) White blue lack of O2 then red Numbness, pain, burning sensation More female

Question 39

Vasodilator drugs

Answer 39

Physiological control of vascular tone -autonomic innervation -circulating hormones -local mediators

Question 40

Indirect vasodilators

Answer 40

I.e drugs which block vasoconstriction -ANS- sympathetic blockade, block a1 receptor, so block vasoconstricting action of NA -RAAS- angiotensin II is vasoconstrictor, block actions get a vasodilator effect- ATII antagonist. Endothelins tend to be vasoconstrictors, drugs that block action of naturally occurring endothelins

Question 41

Direct vasodilators

Answer 41

Influence level intracellular calcium, smooth muscle cells- released from intracellular stores and enters cells through voltage gated Ca2+ channels -> anything that impacts membrane potentials may impact these channels CGMP importance determinant smooth muscle action, affects Ca2+ channel duration can through intermediates effect actin-myosin interaction

Question 42

Clinical uses

Answer 42

Hypertension Angina pectoris: pain due to inadequate coronary blood flow for level of activity, atheromatous obstruction (difficult for a drug to release obstruction), arterial spasm. Drugs: increase coronary flow, decrease cardiac work- if cardiac myocytes working less, less O2 demand, reduced flow less effect

Question 43

Drugs- not vasodilators

Answer 43

Beta blockers- block B1 Receptor on cardiac myocytes reducing activity Ivabradine- inhibits If channel (responsible for pacemaker potential), reduce heart rate Both reduce cardiac work

Question 44

Drugs for angina Organic Nitrates

Answer 44

Glyceryl trinitrate (GTN) most common Isosorbide mono/di nitrate less common Mechanism of action: -NO (through action of guanylate cyclase) increase cGMP-> relaxation. Action on Ca2+ channels and on actin-myosin interaction. Nitrovasodilators -systemic vessels: greatest effect on venous vessels than arterial, greatly reduces venous return, reducing cardiac work, reducing preload , so coronary circulation able to maintain sufficient oxygenation of cardiomycyte -direct effect on coronary vessels, increasing coronary flow. If there’s an obstruction this might help

Question 45

Glyceryl trinitrate (nitroglycerin)

Answer 45

Unwanted effects: -excess vasodilation. Hard to titrate right level of drug -hypotension-> syncope, reflex tachycardia through the baroreceptor reflex -headache- excess vasodilation, patients taking GTN have heart with compromised coronary blood flow so not helpful with blood supply to head and brain Other smooth muscle: -eg GIT, bronchi might also be affected -GIT relaxation of smooth muscle here would result in reduction motility, constipation. Small change in diet or drug would be needed

Question 46

Glyceryl trinitrate (nitroglycerin) administration.

Answer 46

Administration: -sublingual- small tablets or spray under tongue- highly vascularised thin mucosa rapid diffusion of drug into circulatory system -oral route doesn’t work- when absorbed completely metabolised through 1st pass metabolism in liver so never reaches its target -the sublingual route avoids 1st pass metabolism -fast but short duration influences how people take drug, many people take it on a need to know basis not regularly Transdermal for prophylaxis: -patches drug constantly diffusing into body at low level to prevent angina attack -NB: isosorbide mono/di nitrate work in similar way but have different pharmacokinetics so can be given orally, longer duration of action Other therapeutic issues: -physiological tolerance- GTN only working on one factor other pathways can act to counteract effect -pharmacological tolerance- some fundamental change in way drug interacts with target with exposure target to drug system stops responding to drug

Question 47

Calcium channel blockers

Answer 47

Examples: -dihydropyridines DHPs eg amlodipine Verapamil— diltiazem- DHPs Verapamil- relative selectivity for Ca2+ channels on cardiac myocytes Diltiazem- characteristics both verapamil and DHPs action both in heart and vasculature DHPs- relative selectivity for ca2+ channels on vasculature Systemic vessels: Arterial> venous: -decrease TPR, decrease cardiac work decrease oxygen demand of cardiomyocytes. Increase coronary flow?. Overwhelming mechanism of action on systemic vessels Unwanted effects: -flushing- any part/majority of body -decreased GIT activity - affects smooth muscle

Question 48

Clinical use peripheral vascular disease

Answer 48

Raynauds syndrome: -extremely painful -spasm induced by cold weather, within extremities, vasoconstriction -Nifedipine- DHP: —not useful in all individuals- different causes?

Question 49

Clinical use impotence

Answer 49

Erection- corpora cavernosa must fill with blood, highly specialised form vasodilation -physiologically- NO and cGMP control this process Phosphodiesterases degrade cGMP: -inhibition increases cGMP- smooth muscle relaxation, drugs need localised effect. Lots types PDE- differential distribution Sildenafil- viagra: -PDE inhibitor -type 5 -found primarily in genital tissue so Sildenafil can have relatively localised effect -few unwanted effects -interactions: -nitrates: potentially fatal -individuals with problems with vasculature could be taking GTN for angina -other uses; PDE type 5 found in pulmonary vasculature so PDE type 5 inhibitors could be used for pulmonary hypertension

Question 50

Clinical use hair loss

Answer 50

Minoxidil- “regaine” -discovery hypertrichosis-increased hair growth If drug applied topically Use: topical application-> localised vasodilation might support follicles holding onto hair for longer Mechanism: -K+ channel opener will allow K+ to leave -efflux K+ from cells causes Hyperpolarisation-> Ca2+ channels voltage gated so less likely to be open less intracellular Ca2+

Question 51

Clinical use improved cerebral function

Answer 51

Stroke -post haemorrhagic vasospasm: vessels respond by vasoconstricting helpful in reducing blood loss, lasts long time so all territory downstream blood vessel not being supplied, neurones-hypoxic —> dysfunctional or die -calcium channel blockers investigated to counteract this e.g nimodipine Dementia: -vascular dementia -suggested that maintaining cerebral blood flow may hold off symptoms

Question 52

Respiratory influences on heart

Answer 52

Mechanical interaction: -inspiration -> increased venous return to RV, increase right SV (starlings law), increase left EDV and SV Neural interaction: -inspiration-> increase HR, sinus arrhythmia

Question 53

Central nervous mechanisms

Answer 53

Inspiration activates inspiratory motor neurones- phrenic nerves to diaphragm and intercostal muscles Central inspiratory neurones exert inhibitory influences on vagal activity via nucleus ambiguus to heart-> increase HR Therefore HR increases with each inspiration

Question 54

Reflex initiated by pulmonary stretch receptors

Answer 54

Pulmonary stretch receptors in respiratory airways- vagal afferents Inspiration from inspiratory motor neurones leads to widening of airways activates pulmonary stretch receptors in nucleus tractus solitarius which then inhibits nucleus ambiguus and vagal activity

Question 55

2 main mechanisms- both influence cardiac vagal activity and nucleus ambiguus

Answer 55

These 2 mechanisms explain sinus arrhythmia Also when respiration increases,expect increase in heart rate via these mechanisms Eg systemic hypoxia, exercise, stress When respiration decreases expect decrease in HR via reverse of these mechanisms

Question 56

Systemic hypoxia

Answer 56

Fall in PaO2<60mmHg (8.1kPa) Reflex responses- peripheral chemoreceptors sense the fall in PaO2 Reflex responses are superimposed on local responses to hypoxia

Question 57

Reflex effects of hypoxia

Answer 57

Peripheral chemoreceptors: Carotid body: occur bilaterally, internal carotid artery, Glossopharyngeal nerve Aortic bodies in arch of aorta, vagus nerve afferents Peripheral chemoreceptors are stimulated by: - decrease PaO2 -increase in PaCo2 -decrease pH in arterial blood Increase afferent activity to NTS (medulla) They homeostatically regulate PaO2 etc by changing respiration, but changes in respiration affect the cardiovascular system

Question 58

Reflexes from peripheral chemoreceptors

Answer 58

When respiration cannot increase: Primary cardiovascular reflex, decrease HR and vasoconstriction (except brain). O2 conserving by reducing oxygen consumption of heart, bradycardia vasoconstriction reducing blood flow to various tissue reduce oxygen consumption Stimulate inspiratory drive, stimulate NA, stimulate rostral ventral lateral medulla to stimulate sympathetic fibres excitatory effect causing vasoconstriction. When respiration can increase: -effects of increase respiration on HR dominate, ie HR increase -inhibits NA, inhibits vagal activity, increase in respiration widens airways stimulates pulmonary stretch receptors input in NTS

Question 59

Systemic hypoxia when respiration cannot be increased

Answer 59

For example: -under muscle relaxant (paralysed) — pump ventilated at constant rate and depth -after high spinal transection -long dive under water -fetus in utero -severe respiratory disease Chemoreceptors stimulated-> increased afferent activity to NTS, reflex decrease HR and reflex vasoconstriction O2 conserving reflex Superimposed on: (local effects of hypoxia) -decrease HR and depressed contractility, cerebral vasodilation, muscle vasodilation, pulmonary vasoconstriction O2 that is available is directed to brain -pulmonary vasoconstriction may lead to pulmonary oedema, eventually to right ventricular failure In respiratory disease- patient remains hypoxic- blue bloater

Question 60

Systemic hypoxia when respiration can increase:

Answer 60

For example: -hypoxic atmosphere -high altitude -less severe respiratory disease Reflex effects of peripheral chemoreceptors stimulation on heart are overcome by effects of increased respiration on Heart Rate Thus increased respiration and increased HR and generalised vasoconstriction -> as a result of increased sympathetic nerve activity Helps to restore PaO2 (homeostatic) and increased cardiac output -> brain (local vasodilation) Because PaO2 better controlled -tissues do not become as hypoxic -pulmonary vasoconstriction less severe In respiratory disease- pink puffer -arterial PO2 well maintained by increase in respiration.

Question 61

When respiration decreases, expect decreased HR

Answer 61

Eg: reflexes evoked by Trigeminal receptors, cold water on face/nose - diving reflex Stimulation of Trigeminal afferents- NTS (pathway to cardiac vagal motor neurones inhibitory effect, pathway to RVLM excitatory effect- vasoconstriction) -inhibition of central inspiratory neurones (remove influences of sinus arrhythmia pulmonary stretch receptors stimulated less) —expiratory apnoea -decreased HR (increased vagal activity ) removal influences that increase HR -vasoconstriction (increase sympathetic activity) except brain Another oxygen conserving reflex

Question 62

Similar reflex evoked by receptors in facial sinuses, larynx, pharynx

Answer 62

(Ie expiratory apnoea, bradycardia, vasoconstriction) Clinical significance: These receptors may be stimulated by: -sinus washing -irritant vapours, carriers in some aerosols -intubation, bronchoscopy, laryngoscopy etc -lumps of food caught in pharynx or touching larynx -quadraplegics -when mucous aspirated Strong response can cause expiratory apnoea and cardiac arrest even death -“ steak house death” NB: mouth to mouth respiration/ ventilating thorax can terminate apnoea etc and so reverse the reflex, restores rhythmic breathing and heart rhythm On the other hand: -ice bag on the face can be used to stop a supraventricular tachycardia —stimulates Trigeminal receptors- causes apnoea and bradycardia

Question 63

Central neural control

Answer 63

Involves reflex patterns of responses to specific stimuli Receptor-> afferent nerves-> CNS -> efferent nerves/hormones -> effectors heart and blood vessels Often involves respiratory and other systems as well Reflex responses are superimposed on local influences: -heart: (HR, SV)- intrinsic beating, starlings law Arterioles: (resistance)- endothelial, myogenic, metabolic influences Veins: (capacity)- gravity, respiratory pump, muscle pump — affect capillaries- diffusion, filtration CNS may also modulate reflex responses CNS may initiate cardiovascular and respiratory responses- emotion, previous experience, volition etc

Question 64

The baroreceptor reflex

Answer 64

Homeostatically regulates ABP -pressure in arteries Baroreceptors are stretch receptors Increase in stretch-> increase afferent activity and vice versa Afferent activity -> nucleus tractus solitarius NTS

Question 65

Effects of changes in pulsation arterial pressure on baroreceptors afferent activity

Answer 65

Individual receptors have different thresholds ~60mmHg upwards of Respond to magnitude of stretch and Rate of change

Question 66

The baroreceptors reflex response to a fall in ABP

Answer 66

decrease ABP Decrease baroreceptors activity CNS Decreases parasympathetic activity (increases HR, contractility, Increases ESV, increases SV, increases CO) Increases venous vessels constriction increases EDV increases SV Increase in sympathetic activity-> constriction of arterioles, decreases capillary hydrostatic pressure (increases filtration into capillaries increasing EDV) and increases TPR, Increase CO x increase TPR= Increase ABP

Question 67

Baroreceptor reflex pathways

Answer 67

Baroreceptor afferent fibres -> NTS NA= nucleus ambiguus (cardiac vagus neurones) RVLM: is inhibited by BR, main excitatory drive to sympathetic pre-ganglionics CVLM: excited , inhibitory input to RVLM Inhibited sympathetic activity to heart and blood vessel s Decrease in ABP-> decrease baroreceptor activity-> reduction in influences on NA and RVLM -> increase ABP towards normal

Question 68

Reflex influences on arterioles in responses to fall in ABP

Answer 68

Strongest in GIT (25% at rest). Skeletal muscle (20% TPR at rest), skin if not hot Kidney- myogenic dilation if small decrease in ABP Otherwise reflex renal vasoconstriction (20% TPR at rest) and renin release-> angiotensin Brain always shows myogenic dilation - helps to maintain CBF Coronary circulation- functional/exercise hyperaemia- response to increase cardiac work (because reflex increase HR, increase contractility)

Question 69

Pressure Autoregulation

Answer 69

Blood flow remains constant over wide range despite changes in ABP Brain 60-160mmHg Myogenic dilation in low pressure. Myogenic constriction at high pressure Kidney autoregulates over narrower pressure range than brain ~70-120mmHg

Question 70

Functional importance of the baroreceptor reflex

Answer 70

Baroreceptor reflex- topically keeps ABP down Continuously buffers changes in ABP for example: -increase ABP- coughs, sneezes — exercise, particularly static —environmental and mental stressors -decrease ABP: —standing up, dehydration, haemorrhage —redistribution of or reduction in blood volume -> decrease in EDV, decrease in SV, decrease in CO and decrease in ABP NB: sensitivity and set point (level to which ABP is regulated can be changed acutely and chronically)

Question 71

Volume receptor reflex is important in long term regulation of blood volume

Answer 71

Volume receptors and volume receptor reflex Stretch receptors in right atrium -affected by changes in CVP (filling of veins) -afferents -. Via vagus nerve to medulla - affected by real changes in blood volume -by changes in distribution of blood volume standing/sitting/lying Increase stretch increase afferent activity Decrease stretch decrease afferent activity Homeostatically regulate blood volume

Question 72

Volume receptor reflex

Answer 72

Decrease blood volume decrease receptor activity to NTS and then to paraventricular nucleus in hypothalamus -increase sympathetic activity to kidney , renal vasoconstriction decrease renal blood flow, less filtration of plasma in kidney -increase renin release, increase angiotensin II, increased reabsorption of Na+ -increase ADH release from posterior pituitary gland, increased reabsorption of water Decrease urine volume Helps to increase blood volume towards normal increase central venous pressure Increase blood volume-> opposite reflex effects on kidney

Question 73

Volume receptors

Answer 73

Continually monitor “blood volume” -distension of atrium —reflexly adjust sympathetic activity to kidney —and ADH release When used: -decrease distension of atrium- when standing (venous pooling), haemorrhage, dehydration -increase distension of atrium- when supine, large fluid intake by mouth, over transfusion

Question 74

Bringing reflexes together

Answer 74

The reflexes keep ABP and BV at rest, lower than they would otherwise be Baroreceptors and volume receptors continuously monitor and adjust ABP and CVP to individuals own set points Baroreceptor reflex effects on ABP are much faster than volume receptor reflex effects on blood volume Sensitivity and/or set point of baroreceptor reflex can be changed -acutely in exercise, mental stress -chronically in hypertension, heart failure

Question 75

Appropriate responses to naturally occurring changes in ABP require fast and maintained baroreflex adjustments

Answer 75

From sitting to standing Fall in ABP Heart rate falls when BP falls due to baroreceptor reflex Fall in SV delayed and there’s initial increase in CO and fall in TPR Skeletal muscle pump causes the initial increase in CO, more muscle more pronounced effect Venous pooling continues when standing up, SV is reduced Maintenance of ABP involves maintained baroreflex peripheral vasoconstriction (increase SNA) Maintained persistent increase in TPR due to reflex vasoconstriction, takes longer to increase than the increase in HR sympathetic effect on blood vessels slow because length of pathway is longer

Question 76

How does crouching raise ABP

Answer 76

Skeletal muscle pump, squeeze blood out venous vessels back to heart. Less venous pooling less distance from heart so effect of gravity is less. Venous vessels compressed—> reducing capacity, increase TPR contracting leg muscles