Week 11 Physiology - CVS Autoregulation, Special Circulations

Question 1

What types of blood vessels contain smooth muscle and receive motor fibres from from SNS?

Answer 1

All blood vessels aside from capillaries and venules

Question 2

What anatomical location of the CNS is largely responsible for sympathetic nerves controlling vasculature?

Answer 2

Rostral ventrolateral medulla

Question 3

What factors directly stimulate Rostral ventrolateral medulla?

Answer 3

CO2
Hypoxia

Question 4

Describe Cushing’s reflex and the role of the Rostral ventrolateral medulla?

Answer 4

RVLM in the setting of raised ICP will have decreased blood supply (Monroe Kelly) and therefore will have an excitatory input to increasing BP via SNS activity. This will have a feedback effect via carotid baro-receptors, causing reflex decrease in heart rate (bradycardia)

Remember, Cushing’s triad:
- Hypertension
- Bradycardia
- Decreased respiratory rate

Question 5

What are baroreceptors?

Answer 5

“Stretch” receptors that monitor pressure, located within walls of heart and blood vessels

Question 6

Where are “high pressure” baroreceptors located?

Answer 6

Carotid sinus
Aortic arch

Question 7

Where are “low pressure” baroreceptors located?

Answer 7

R+L atria
Cardiac entrance of SVC + IVC
Pulmonary veins

Question 8

Where are ‘cardiopulmonary baroreceptors’ located?

Answer 8

Endocardial surface of ventricles

Question 9

In what layer of blood vessels are baroreceptors located?

Answer 9

Adventitia

Question 10

What “stimulates” baroreceptors?

Answer 10

Blood vessel distension

Question 11

Describe the pathway of the baroreceptor reflex:

Answer 11

1. Afferent fibres of the carotid sinus = branch of glossopharyngeal nerve, aortic arch = vagus
2. These afferents pass to medulla, with most ending in nucleus of tracts solitaries
3. Results in glutamate release, stimulates excitatory projections into from the NTS to the vagal motor neurons (of various nuclei)
4. Result of baroreceptor discharge = inhibition of tonic discharge of SNS at RVLM and excites vagal stimulation of the heart

Question 12

What are the effects of discharging from baroreceptor vagal efferents?

Answer 12

vasodilation, venodilation, decreased BP, bradycardia, decreased cardiac output

Question 13

What is the Bezold-Jarisch reflex?

Answer 13

Bradycardia, hypotension, and brief apnoea, followed by rapid shallow breathing

Question 14

What is the theorised mechanism of the Bezold- Jarisch reflex?

Answer 14

Inhibitory mechanoreceptors in the left ventricle (particularly the inferoposterior wall). Stimulation of these inhibitory cardiac receptors by stretch (poorly filled ventricle), increases renin and vasopressin release and parasympathetic activity and inhibits sympathetic activity.

Question 15

How does Bezold-Jarisch reflex explain vasovagal syncope?

Answer 15

I.e. venous pooling –> drop in pressure sensed in carotid sinus –> SNS stimulation –> increased contraction of underfilled heart –> paradoxical activation of parasympathetic nervous system and transient but marked hypotension and poor perfusion to CNS –> syncope

Question 16

What is the valsalva manoeuvre?

Answer 16

Forced expiration against a closed glottis

Question 17

Describe the sequence of events in the valsalva manoeuvre and how it leads to vagal stimulation?

Answer 17

1. Increase in blood pressure at onset of straining
2. BP falls as intrathoracic pressure continues to rise and compresses veins, decreasing venous return to the heart
3. Decreased atrial and pulse pressure inhibits baroreceptors, causing tachycardia and rise in TPR
4. Glottis is opened, intrathoracic pressure returns to normal, cardiac output restored, but peripheral vessels are constricted, causing inc. in BP and strongly stimulating baroreceptors –> bradycardia (also the mechanism of how defecation syncope happens)

Question 18

What is the (simplified) components of chemoreceptor reflex arc?

Answer 18

1. Inputs
2. Integration and control centre
3. Effectors

Question 19

Where are peripheral chemoreceptors located?

Answer 19

Carotid and aortic BODIES (not sinuses)

Question 20

What is the primary and secondary factors that stimulate peripheral chemoreceptors?

Answer 20

Primary = Decreased PaO2 (stimulated by low O2 tension)
Secondary = Decreased PaCO2 (20% response of that causes by decreased PaO2)

Question 21

Where are central chemoreceptors, and how are they stimulated?

Answer 21

Located on the ventral medulla, and are stimulated by a fall in CSF pH

(Remembering that ions cannot cross BBB, but CO2 freely can, which then combines with H20 in CSF to form H2CO3 –> H+ and HCO3 - –> pH sensitive stimulation of effector arm

Question 22

Other than increased minute volume, what other effects can chemoreceptors have?

Answer 22

Vasoconstriction
Increased vagal nerve activity

Question 23

What substances are secreted by the endothelium, and what vasomotor activity do they display?

Answer 23

1. Prostacyclin –> vasodilation
2. Thromboxane A2 –> vasoconstriction
3. Nitric Oxide/Endothelium-derived relaxing factor (EDRF) –>vasodilation (inhibited by Hb)
4. Endothelins –> vasoconstrictive

Question 24

What is the mechanism by which NO causes vasodilation?

Answer 24

Produced by endothelium (activated by ACh, bradykinin) –> diffuses from endothelium to vascular smooth muscle cells –> activates guanylyl cyclase –> cGMP –> second messenger that causes decreased Ca2+ entry, hyper polarisation and de-phosphorylation of the myosin light chains –> decreased contraction

Question 25

What potent vasoconstrictor is increased in CCF?

Answer 25

Endothelin-1
(Not stored in granules)

Question 26

Describe physiological response to 1L of blood loss:

Answer 26

1L = 20% circulating blood volume

1. Baroreceptor reflex –> tachycardia
2. Sympathetic activation + catecholamine release –> vasoconstrictive effects, redistribution of circulation away from cutaneous and splanchnic circulation, sympathetic stimulation of ADH and renin
3. Vasoconstriction of arterioles –> decreased hydrostatic pressure –> increased water intravascularly, but diluted haematocrit
4. Renal fluid and electrolyte conservation and increase in erythropoiesis

Question 27

What are metabolites responsible for vasodilation?

Answer 27

CO2, Lactate, H+, low O2, histamine, adenosine, K+ (hyper polarises SM cells)

Question 28

What metabolites are responsible for vasoconstriction?

Answer 28

Serotonin from platelets after vascular injury
Decreased tissue temperature

Question 29

What is the formula for cerebral perfusion pressure?

Answer 29

CPP = Mean arterial pressure - intracranial pressure

Question 30

What is the normal flow rate of blood to the brain, and its percentage of cardiac output?

Answer 30

50ml/100mg/min (usually 750ml per brain per minute!)

Usually 15% cardiac output

Question 31

What is autoregulation of cerebral blow flow?

Answer 31

“A homeostatic process that regulates and maintains cerebral blood flow (CBF) constant and matched to cerebral metabolic demand across a range of blood pressures.”

Question 32

What is the rough range of MAP that brain can maintain constant/autoregulation of flow?

Answer 32

50-150mmHg

Question 33

What is the Monroe-Kelly doctrine?

Answer 33

Cranium is a fixed volume, and therefore remains constant.

Increases in venous pressure/CSF/tumour/mass = decreased cerebral blood flow by decreasing perfusion pressure and compression of cerebral vessels

Question 34

What metabolic mediators are responsible for changes in cerebral vascular autoregulation?

Answer 34

• Carbon dioxide concentration in the brain parenchyma
• pH of the blood
• Lactate
• Potassium
• Low oxygen

Question 35

What mechanical factors are responsible for autoregulation in cerebral vasculature?

Answer 35

Autonomic innervation (cholinergic neurons)
Vasodilatory Endothelial factors (substance P, neurokinin-A
Vasoconstrictive Endothelial factors (neuropeptide Y)
Myogenic (constriction in response to increase stretch/pressure to prevent increased flow)

Question 36

What is the percentage of cardiac output that supplies the heart?

Answer 36

5% - 50-120mL/100mg cardiac mass

Question 37

When does the majority of flow to the cardiac muscle occur?

Answer 37

Diastole - 75% flow to LV and 50% flow to RV

Flow less impaired to right side of heart during systole, and so tachycardia more effect on LV perfusion

Question 38

Why is it important that the heart can auto regulate flow?

Answer 38

Already extracts close to maximal amount of O2 at resting heart rate, therefore if increased metabolic demands, requires increased blood supply

Question 39

What factors increase flow/vasodilation through coronary arteries?

Answer 39

SNS –> B2 agonism, muscarinic agonism on vasculature
CO2, low pH, increased K+, lactate, low O2

Question 40

Briefly, describe uteroplacental blood flow:

Answer 40

1. Blood comes from anastomosis of uterine and ovarian arteries, with radial branches penetrating through myometrium to endometrial surface
2. Spiral arteries then suppy the intervillous space (a 150-500ml blood reservoir)
3. Chorionic villi project into the intervillous space, and interface with maternal blood

Question 41

Is there autoregulation of uterine/placental blood flow?

Answer 41

No! There is no means to increase or regulate flow in the low pressure system that is uteroplacental circulation - however there is significant ability to increase O2 extraction to meet increasing metabolic demands.

Also, vessels increase in size significantly, and flow over the duration of the pregnancy increases 20x