Rohit Ramchandra

Question 1

What determines the HR?

Answer 1

SA node and ANS

Question 2

What determines SV?

Answer 2

Input to the heart

Frank starlings law - stretch = greater force

Question 3

Where is sympathetic input of the vasculature strongest?

Answer 3

Arterioles and precapillary vessels.

Little in the capillaries, slightly more post capillary.

Postcapillary vessels also have a smaller proportion of smooth muscle

Question 4

How does autoregulation work?

Answer 4

Partly by the myogenic hypothesis. Changes in perfusion pressure cause stretch of the vessel which leads to contraction.

You with initially get changes in flow but this then adjusts to maintain the initial flow. It does this by changing the diameter of those vessels.

40 to 140 mmHg

This happens in muscles

Question 5

What is an example of autoregulation?

Answer 5

Reactive hyperaemia.

This is when a blood vessel is occluded for a short period. When that occlusion is released blood flow rises above the re-occlusion level and this hyperaemia is maintained for the duration that the vessel was occluded.

Question 6

How is blood flow controlled locally?

Answer 6

Autoregulation

The myogenic hypothesis:
Increased perfusion increases the vascular pressure throughout the circulation. Increased transmural pressure leads to vascular distension. Th stretch elicits smooth muscle contraction.

Metabolic hypothesis:
Skeletal and cardiac muscle. Exercise cause the release of metabolites by that exercising muscle that causes vasodilation to increase blood supply. Supply and demand.
These metabolites are lactic acid, which increase H+ ions, K+, and adenosinde and adenine nucleotides. Osmolarity also has a role.
The metabolites have the greatest effect in the precapillary vessels. Increased flow -> increased precapillary pressure -> more blood flow into tissue.

Endothelium releases NO, which acts as a vasodilator. Increased blood flow increases shear stresses acting on the endothelium, which leads to the release of NO. This counteracts the myogenic hypothesis.
NO synthetase converts L-argenine into NO, which stimulates the production of cGMP.

ATP released from cells with low O2 causes vasodilation.

In addition, the sympathetic nerves take a global view of the situation and redistribute blood. Change the diameter of blood entering organs. A decrease in sympathtic drive to muscle causes vasodilation and increase sympathetic supply to other areas that don’t need blood.

Question 7

What happens to blood flow in someone who has a car accident and looses blood? Exam question

Answer 7

Baroreflex and cardiopulmonary reflex.

As blood pressure falls what happens to peripheral reflex and blood flow to organs.

If the patient is immobile then the metabolite hypothesis will explain why the vital organs will retain blood flow because they will still be functioning, creating metabolites and inducing vasodilation. The decrease in stretch due to the decrease in the blood volume will also cause vasodilation by the myogenic hypothesis. The endothelium will have reduced shear stress and therefore will produce less NO and promote vasoconstriction.

Increased sympathetic drive to he organs and tissues that need less blood.

There is no metabolism induced vasodilation to the skin because the flow is already much higher than demand. So Blood flow to the skin is reduced in blood loss because of sympathetic stimulation.

Ang II produced increase the vasoconstriction induced.

Question 8

What happens if you have noepinephrine bind to an alpha 1 or an alpha 2 receptor?

Answer 8

Alpha 1 receptor: the alpha one receptor is found in the postjunctional membrane and bindingactivates a G protein which activates phospholipase C. This then causes IP3 release which increases the intracellular Ca2+ concentration and allows contraction of the smooth muscle surrounding blood vessels

Binding to alpha 2 receptors on the post-junctional membrane causes the activation of a G protein that inhibits adenylate cyclase causing decreased levels of cAMP. This decreases PKA and its ability to store Ca2+ thus causing vasoconstriction. Beta 2 receptors do the opposite

Binding of alpha 2 receptors on the presynaptic membrane causes closure of the Ca2+ channels inhibiting the release of noreadrenaline and therefore causing vasodilation. Other inhibitory molecules can do this.

Whether you get contraction or dilation depends on the amount and ratio of the receptors available.

Question 9

What can increase or decrease the function of norepinephine in adrenergic nurotransmission?

Answer 9

Inhibitory products around the neuron decrease it's function. This includes:
Acetylcholine
Adenosine
Dopamine
Histamine
Prostaglandins E1 and E2

Excitatory:
Angiotensin II
Adrenaline

Question 10

What can alter sympathetic drive?

Answer 10

The amount of inhibitory or excitatory molecules or the number of receptors present.

Question 11

What is cholinergic innervation?

Answer 11

Nerves where acetylchonine is the neurotransmitter.
For blood vessels, this is largely parasympathetic.

Leads to an increace in ACh in the blood. ACh in the blood binds to M3 muscarinic receptors in the endothelium stimulating the release of NO and causing vasodilation.
If the endothelium is absent then ACh acts directly on the smooth muscle and causes vasoconstriction.

Question 12

What does circulating levels of noradrenaline do to the blood flow to various organs?

Answer 12

Noradrenaline decreases blood flow to the skeletal muscle, skin, kidney and splanchnic.

Question 13

What does circulating levels of adrenaline do to the blood flow to various organs?

Answer 13

Increased flow to skeletal muscle and splanchnic tissues.

Decrease flow to the skin and kidneys
The different effects are caused by the different receptors.

Question 14

What are the different adrenergic receptors affinity for catecholamines?

Answer 14

Alpha: adrenaline > noradrenaline > isoprenaline

Beta2/alpha 2: isoprenaline > adrenaline > noradrenaline.

Question 15

During exercise, what has a greater effect, the sympathetic drive or the metabolic hypothesis?

Answer 15

Sympathetic system cause vasoconstriction, therefore the metabolic hypothesis must have a stronger effect.

This is not true for the skin, which is more sensitive to sympathetic stimulation.

It is overridden by increases of the adrenergic neurotransmitter inhibitors (aacetylcholine, adenosine, histamine etc.)

Question 16

What controls blood flow to the skin?

Answer 16

Very little metabolic hypothesis induced change because the blood supply to the skin is in excess of the metabolic requirement. Therefore, blood low to the skin is determined by the sympathetic innervation.

When your temperature decreases then you vasoconstriction to the skin to reduce blood flow.
Affinity of alpha receptor for noradrenaline increases as local temperature decreases and vice versa. This causes vasoconstriction.

Question 17

What is autoregulation in cerebral circulation?

Answer 17

Autoregulation of perfusion between 60 and 180 mmHg. Controlled by local factors.
Perivascular pH and pCO2 and K+ important vasodilator molecules.

This is controlled locally by PaCO2 levels and pH, which drives vasodilation

Question 18

What is the cause of low haemoglobin in someone with GI bleeding?

Answer 18

Loss of iron

Question 19

What drives increased CO in someone with a cronic bleed?

Answer 19

Central chemoreceptors (CNS)
Peripheral chemoreceptor (aortic and carotid bodies)

Question 20

What happens to the CO and peripheral resistance in someone with GI bleeding?

Answer 20

CO increases and total peripheral resistance decreases.

The decreased TPR is caused by vasodilation (metabolic hypothesis is trying to vasodialte to increase blood volume).

These is increased sympathetic drive to the heart to increase heart rate but in periphery this is overcome by the metabolic hypothesis.

TPR has to be reduced because the MAP is the same and MAP = TPR x CO and CO is elevated.

Question 21

What causes systolic murmur in a patient with increased CO?

Answer 21

Because they have changes in the blood resulting in turbulent flow.

Question 22

Why is someone with blood loss pale and cold?

Answer 22

Because they are anemic. They have reduced blood flow to the skin, which cause the skin to be pale and cold.

She is listless because of the effort required to increase CO or reduced oxygen to the brain.

Question 23

Why can you have a pulse with compartment syndrome but not blood getting to the fingers?

Answer 23

Because the pressure within the tissue has increased due to the bleeding or swelling. The pressure is sufficient to stop fluid from leaving the vessel and entering the tissues to oxygenate but is not sufficient to completely block blood flow in the vessels (it would need to be as high as systolic bp to completely block).

Question 24

How do you differentiate between cardiogenic pulmonay odema and noncardiogenic pulmonary odema?

Answer 24

The fluid will be protein rich in non-cardio.

Brain natriuretic peptide (BNP) and Troponin T levels in the blood indicate cardiac damage.

Chest X-ray

Blood cultures. WBC count.

History of MI.

Question 25

Why does heart rate increase with excessive bleeding?

Answer 25

Cardiopulmonary receptors in the atria, ventricles and pulmonary arteries sense low pressure.

Baroreflex in the aortic arch and carotid sinus senses decreased MAP and increases heart rate

Question 26

Why does the haemocrit change with excessive bleeding?

Answer 26

Because of the vasoconstriction in the precapillaries. This causes an increased absorption of fluids in the capillary which dilutes the haemocrit.

Question 27

What is circulatory shock?

Answer 27

It is when ischaemia caused by reduced blood causes loss of perfusion of the walls of blood vessels and so they can’t maintain the vasoconstriction that happens with blood loss.
The sympathetic drive that causes the release of NA to cause vasoconstriction happens so much that the nerves run out of NA. Thus, the sympathetic function is reduced.
All the metabolites released also induces vasodilation. Together this causes a sharp decrease in blood pressure.

Give hypertonic saline to draw fluid back into the capillaries

Question 28

What stimulates the alpha 1 receptor and what does it do?

Answer 28

Sympathetic release of norepinephrine stimulates the alpha 1 receptor. This leads to activation of the G protein Gq, which activates phospholipase C. This leads to the release of DAG and IP3, which increase intracellular Ca -> contraction.

Question 29

What stimulates the alpha 2 receptor and what does it do?

Answer 29

Sympathetic release of norepinephrine stimulates the alpha 2 receptor. This inhibits the activation of adenylate cyclase.

Decreased cyclic AMP -> decreased protein kinase A -> decreases efflux and storage of Ca (reduced relaxation) -> constriction.

Alpha 2 receptors are also on the presynaptic membrane.

Question 30

What receptors does actylcholine bind in vessels?

Answer 30

M3 receptors in the endothelium inducing NO release and vasodilation.

Question 31

What happens to CO and TPR in severe blood loss?

Answer 31

Sympathetic drive increases HR, which increases CO.

TPR is decreased because of the metabolic hypothesis.

There is an increased sympathetic drive but the metabolic hypothesis wins out.

Question 32

Where are the systemic arterial baroreceptors?

Answer 32

In the carotid sinus and aortic arch

Question 33

What does having a baroreceptor reflex that doesnt work very well indicate?

Answer 33

That you are more likely to have a higher rate or mortality.

Question 34

What stimulates baroreceptors?

Answer 34

Stretch sensitive ion channels - stretch causes their activation.

They sense the stretch and the difference in pressure inside and outside the vessel.

They maintain blood pressure around a specific set point. The baroreceptors do not control that set point. Cardiac receptors do.

Question 35

As blood pressure elevates, what does this do to carotid sinus stimulation and vagus and sympathetic firing?

Answer 35

Incerease pressure -> increased baroreceptor firing -> vagus increased -> sympathetic decreased through an inhibitory neuron pathway -> decreased HR.

Cardiac receptors control the mean arterial pressure set point more than the baroreceptors.

Question 36

What happens when that stimuli to the carotid sinus is pulsatile?

Answer 36

It increases the firing from the sinus

Question 37

What does stimulation of the systemic baroreceptors cause when BP decreases?

Answer 37

Increased HR
Increased ionotropy
Venoconstriction
Constriction of precapillary vessels
Increased circulating levels of ADH, Ang II (increases thirst), aldosterone
Increase sympathetic stimulation of the kidney.

Question 38

What causes cardiac receptors to fire?

Answer 38

They sense volume. Send info to the brain about volume status.

Are in the heart.

Question 39

What happens when cardiac receptors fire?

Answer 39

Reduced renal sympathetic stimulation - increased urine output.

Question 40

What do the osmoreceptors do and where are they?

Answer 40

In the hypothalamus.

Neurons that sense osmolarity. Are stretch sensitive neurons. When the blood osmalarity is high then the fluid leaves the neruon causing itto shrink andvise versa.
This modulares the synthesis and release of ADH.

Question 41

What does a peripheral chemocreceptor do?

Answer 41

In carotid arteries.

Stimulated in response to low pH and PaO2.
Sensing the O2 going to the brain.
It stimulates increased sympathethic drive to the heart and vessels.
Stimulates breathing.

If this is stimulated abnormally then it will cause hypertension that is unresponsive to drugs.

Question 42

What is the biggest difference between the ECF in the plasma and in the interstitial fluid?

Answer 42

In the plasma there are proteins, this creates the colloid pressure gradient. Osmotic pressure gradient that pulls fluid into the plasma.

Albumin is the main protein.

Question 43

What drives movement of water into or out of the cells?

Answer 43

Osmotic pressure. Primary by the osmotic pressure in the ECF.

Question 44

When blood pressure decreases, why does ESF move into the vessels?

Answer 44

Because the sympathetic tone in the precapillary vessels, combined with the lower BP means that the pressure in the capillary is low and therefore more water is absorbed. This occurs until the proteins in the plasma are diluted.

Question 45

What happens in blood loss of less than 10%?

Answer 45

Mean arterial pressure is maintained (no baroreceptor firing) although pulse pressure is reduced. This is called nonhypotensive haemorrhage.

There is a response from the cardiopulmonary receptor.

Question 46

What happens with blood loss of >10%

Answer 46

There is a graded fall in systemic arterial pressure. Called hypotensive haemorrhage.

Associated with sympathetic activation.

Question 47

What might happen when there is extreme blood loss (>30%) for long periods?

Answer 47

May get haemorrhagic shock. When restoring the volume may not help.

Question 48

What is more sensitive, the baroreceptor or the cardiacreceptors?

Answer 48

The cardiac receptors.

Less than 10% change in volume does not cause a change in pressure.

Question 49

What happens when you go from lying down to standing?

Answer 49

Increased pressure in veins causes blood to leave the vessels. This decreases SV and causes a decrease in CO. TPR increases and the HR increases to accomidate.

Question 50

What happens to baroreceptor firing when you are chronically hypertensive?

Answer 50

The baroreceptors reset and adapt to the new normal high blood pressure.