Lecture 15; Arterial pressure, long term regulation

Question 1

Describe the flow diagram for hormone release in hypertension (refer to notes and draw it id need be)

Answer 1

Hypertension
= Increase wall tension (law of leplace)
= increased ANG2, VGF, Endothelin, oxidative stress etc
= cardiac remodelling (hypertrophy), pressure overload, thicker stiff ventricles, smaller lumen

Question 2

Describe the interlationship between blood pressure and other disease

Answer 2

Higher blood pressure =

• increased MI, Stroke
• Small decreases in blood pressure represent huge decrease in risk

Question 3

Describe the law of leplace in cardiac hypertrophy;

Answer 3

T = (P . r) / 2h (thickeness)

Question 4

For real learn the diagram in the start of your notes

Answer 4

when you have spare time

Question 5

Describe the equation of BP

Answer 5

BP = CO x TPR

Question 6

Describe the factors that influence TPR;

Answer 6

SNS
= Vasoconstriction, A1
= Vasodilation, B2

Local autoregulation

Humoral
Vasodilation
= prostaglandins, kinins
Vasoconstriction
= ANG, ADH, Catecholamines

Question 7

Describe the factors that influence CO

Answer 7

Cardiac

• HR
• Inotropic state, afterload, preload
• Neural
• Hormonal

Renal fluid volume control

• Renin, ANG2
• Pressure natriuresis
• Aldosterone
• Atrial Natriuretic factor

Question 8

What is the first fundamental feature of BP control?

Answer 8

Blood pressure regulation is integrated into CV and renal function to serve total body homeostasis

Question 9

What is the second fundamental feature of BP control?

Answer 9

Different mechanisms dominate in BP control over different time scales

Question 10

What is the third fundamental feature of BP control?

Answer 10

BP control comprises of multiple mechanisms and a high amount of redundancy i.e backups to cope with change in environmental factors

i.e loss of baroreceptors doesnt mean loss of BP

Question 11

Describe how good the body is at controlling blood pressure with changing environmental factors

Answer 11

Haemorrhage = 1L loss, no change in BP therefore dont measure BP if suspect internal bleeding

2L loss = change in BP
40% blood loss = irreversible shock
40+% loss BV = even with blood given tissue has already being damaged and organ damage is irreversible.

Question 12

What are the short term neural reflexes?

Answer 12

Baroreceptor reflex
Chemoreceptor reflex
CNS isheamic response

Question 13

Describe the CNS ischeamic response;

Answer 13

Responds to high CO2 or low pH as a response to decreased brain blood flow to increased TPR

Question 14

Describe the local mechanisms of arterial pressure regulation;

Answer 14

• Autoregulation by local factors and myogenic response

- Capillary fluid shift

Question 15

Describe the hormonal responses in atrial pressure regulation

Answer 15

• RAA system
• ADH
• ANP
  (All of which influences the kidney function, also stimulation of EPO)

Question 16

Describe volume regulation in the kidney via pressure natriuresis;

Answer 16

Long term regulation of blood pressure
- Intrinsic mechanism whereby increased arterial pressure results in increased renal output of H2O (pressure diuresis) and salt (pressure natriuresis)

Question 17

Describe blood pressure regulation over time;

Answer 17

There are multiple pathways for regulating blood pressure that dominant control over different time scales

• Baroreflex occurs first
• chemoreceptor reflex (Small) and CNS ischemic response (large) occur around the same time)
• Renal body flow is long term control

high amount of redundancy

Question 18

How is the CV system integrative?

Answer 18

Brain and kidney are integrated for control of the CV system

Question 19

What provides short term control of BP?

Answer 19

The baroreflex

Question 20

What are the inputs of the baroreflex?

Answer 20

Arterial baroreflex = High BP = Aortic arch + carotid sinus

Cardiopulmonary baroreflex = Low BP =receptors = atrium and lungs

Question 21

Describe the integration of the baroreflex;

Answer 21

Afferent fibres; 
to medulla
- NTS, the project to;
- NA
- CVLM, RVLM

Question 22

What are the outputs of the baroreflex?

Answer 22

Reciprocal changes in vagal and sympathetic nerve activity to influence CO and peripheral resistance

i.e

AS MAPB increases , renal SNA decreases but HR increases

Question 23

What is the first point in arguing against the baroreflex being a part of long term BP control;

Answer 23

1) Baroreflex reset; That is the operating point is not static but may shift in the direction of a maintained change in pressure

Question 24

What is the evidence supporting the baroreflex reset;

Answer 24

Baroreflex resetting with age and exercise

Summery data demonstrating the modelled carotid baroreflex stimulus response curve from rest to moderate intensity cycling in young and old people

• Sustained increased in arterial pressure (age) shifts the curve to the right
• Exercise increases this up and to the right, mostly due to central command

i.e baroreflex is sustained but at a heightened BP

Question 25

What is the second point in arguing against the baroreflex being a part of long term BP control;

Answer 25

Removal of the baroreceptors does not later MABP, more variable but not chornically altered (multiple blood pressure mechanisms in play over time)

Question 26

What is the third point in arguing against the baroreflex being a part of long term BP control;

Answer 26

The gain of the barorelfex is not sufficient to maintain a constant pressure

Question 27

Describe blood flow to the kidney;

Answer 27

180L per day
1.4L urine
20-25% CO at rest

Question 28

Describe some evidence that the kidneys play a role in long term BP regualtion

Answer 28

Spontaneously hypertensive rat receives a third kidney = blood pressure decreases

But But only if the third kidney has come from a rat without hypertension thus why we dont give kidneys from hypertensive patients

Question 29

What did athur guyton demonstrate?

Answer 29

Lots…..

Demonstrated that mostly the need of the body tissues for o2 determined CO rather than the pumping availability of the heat itself

Fluid intake determines BP thus fluid excretion balances BP

Question 30

Describe how BP is determined by BV

Answer 30

Increased fluid = increased BV = increased venous return = increased CO
= increased BP

Question 31

In the absence of hormones what does increased blood pressure result in?

Answer 31

Increased diuresis and natriuresis

Question 32

What is the equation for excretion?

Answer 32

Excretion = filtration + secretion - reabsorption

Question 33

Describe what happens in the kidneys when BP increases

Answer 33

Increased blood pressure =

• Small increase in filtration (autoregulation mainly keeps this constant)
• Decrease in tubular re-absoprtion (tubular feedback)
  
  • -> Reduced number of Na-H antiporter and reduced Na-K ATPase activity in proximal tubule
  • -> Reduction in sodium resorption in proximal tubule
  • -> Reduction in water resorption in proximal tubule
•  Increased urine output

Question 34

Describe autoregulation in the kidney;

Answer 34

• Blood flow to the kidney is tightly regulated, thus glomerular filtration rate is relatively constant
• BUT Urine output is directly proportional to renal pressure (even though filtration remains constant)

Question 35

describe the summery of the Guyton model of long-term blood pressure control

Answer 35

Long-term control of blood pressure is a question of blood volume/body fluid regulation

An increase in arterial pressure increases urine output by way of pressure diuresis.

Any disturbance which alters peripheral vascular resistance or cardiac function without influencing pressure natriuresis will have no long term effect of arterial pressure! (as blood volume is increased)

Question 36

What does a shift in renal output curve mean?

Answer 36

Hypertension right shifts the curve

Question 37

Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;

point 1

Answer 37

1. All experimental “secondary forms” of hypertension require some maneuver that alters the kidneys ability to excrete sodium and water

Question 38

Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;

point 2

Answer 38

2. In human essential hypertension and genetic rat models of hypertension kidney function is altered

Question 39

Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;

point 3

Answer 39

3. All effective anti-hypertensive agents studied to date have actions that promote sodium and water excretion

Question 40

Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;

point 4

Answer 40

4. Transplantation of a hypertensive kidney into a normotensive rat raises arterial pressure and vice versa.

Question 41

What are the two main causes of renovascular hypertension

Answer 41

The two main causes:
•atherosclerosis- deposits of plaques in the arteries
•fibromuscular dysplasia- muscle and fibrous tissues of the renal artery wall thicken and harden into rings.

Question 42

What are the experimental models of hyperntesion?

Answer 42

Surgical:
- Goldblatt model
- 2K-1C Pharmacological
- Angiotensin II infusion - DOCA salt
- NO blockade
Genetic
- Dahl Salt senstitive
- SSH
ALL have impaired renal function

Question 43

How are pressure diuresis curves formed?

Answer 43

Perfusing a kidney in isolation i.e no nerves of hormones

Question 44

Describe the pressure diuresis curve;

Answer 44

Exponential curve
- no hormones or nerves (these can make it straight up and down)

Must be able to reproduce this curve
x axis = Arterial pressure mmHg
Y axis = Urinary sodium or water output (times normal)

(Y) 1 = normal, (X) ~100mmHg = equilibrium point

Question 45

Go through the slides and learn all points with an exclamation mark!

Answer 45

now

Question 46

What happens to CO if you lose an arm?

Answer 46

It reduces as CO depends on oxygen needed by tissues, and now less tissue

Question 47

Describe the pressure natriuresis curve comparing chronic and acute homeostasis;

Answer 47

Acute curve - exponential curve that covers a lot of pressures (not under hormone or neural response)
Chronic - curve is nearly vertical (hormones and nerve inputs) thus little change in pressure = huge change in Na output (this is known as infinite gain as can change pressure dramatically as baroreflex can only do 7mmHg)