Lecture 15; Arterial pressure, long term regulation Flashcards
Describe the flow diagram for hormone release in hypertension (refer to notes and draw it id need be)
Hypertension
= Increase wall tension (law of leplace)
= increased ANG2, VGF, Endothelin, oxidative stress etc
= cardiac remodelling (hypertrophy), pressure overload, thicker stiff ventricles, smaller lumen
Describe the interlationship between blood pressure and other disease
Higher blood pressure =
- increased MI, Stroke
- Small decreases in blood pressure represent huge decrease in risk
Describe the law of leplace in cardiac hypertrophy;
T = (P . r) / 2h (thickeness)
For real learn the diagram in the start of your notes
when you have spare time
Describe the equation of BP
BP = CO x TPR
Describe the factors that influence TPR;
SNS
= Vasoconstriction, A1
= Vasodilation, B2
Local autoregulation
Humoral Vasodilation = prostaglandins, kinins Vasoconstriction = ANG, ADH, Catecholamines
Describe the factors that influence CO
Cardiac
- HR
- Inotropic state, afterload, preload
- Neural
- Hormonal
Renal fluid volume control
- Renin, ANG2
- Pressure natriuresis
- Aldosterone
- Atrial Natriuretic factor
What is the first fundamental feature of BP control?
Blood pressure regulation is integrated into CV and renal function to serve total body homeostasis
What is the second fundamental feature of BP control?
Different mechanisms dominate in BP control over different time scales
What is the third fundamental feature of BP control?
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
Describe how good the body is at controlling blood pressure with changing environmental factors
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.
What are the short term neural reflexes?
Baroreceptor reflex
Chemoreceptor reflex
CNS isheamic response
Describe the CNS ischeamic response;
Responds to high CO2 or low pH as a response to decreased brain blood flow to increased TPR
Describe the local mechanisms of arterial pressure regulation;
- Autoregulation by local factors and myogenic response
- Capillary fluid shift
Describe the hormonal responses in atrial pressure regulation
- RAA system
- ADH
- ANP
(All of which influences the kidney function, also stimulation of EPO)
Describe volume regulation in the kidney via pressure natriuresis;
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)
Describe blood pressure regulation over time;
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
How is the CV system integrative?
Brain and kidney are integrated for control of the CV system
What provides short term control of BP?
The baroreflex
What are the inputs of the baroreflex?
Arterial baroreflex = High BP = Aortic arch + carotid sinus
Cardiopulmonary baroreflex = Low BP =receptors = atrium and lungs
Describe the integration of the baroreflex;
Afferent fibres; to medulla - NTS, the project to; - NA - CVLM, RVLM
What are the outputs of the baroreflex?
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
What is the first point in arguing against the baroreflex being a part of long term BP control;
1) Baroreflex reset; That is the operating point is not static but may shift in the direction of a maintained change in pressure
What is the evidence supporting the baroreflex reset;
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
What is the second point in arguing against the baroreflex being a part of long term BP control;
Removal of the baroreceptors does not later MABP, more variable but not chornically altered (multiple blood pressure mechanisms in play over time)
What is the third point in arguing against the baroreflex being a part of long term BP control;
The gain of the barorelfex is not sufficient to maintain a constant pressure
Describe blood flow to the kidney;
180L per day
1.4L urine
20-25% CO at rest
Describe some evidence that the kidneys play a role in long term BP regualtion
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
What did athur guyton demonstrate?
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
Describe how BP is determined by BV
Increased fluid = increased BV = increased venous return = increased CO
= increased BP
In the absence of hormones what does increased blood pressure result in?
Increased diuresis and natriuresis
What is the equation for excretion?
Excretion = filtration + secretion - reabsorption
Describe what happens in the kidneys when BP increases
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
Describe autoregulation in the kidney;
- 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)
describe the summery of the Guyton model of long-term blood pressure control
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)
What does a shift in renal output curve mean?
Hypertension right shifts the curve
Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;
point 1
- All experimental “secondary forms” of hypertension require some maneuver that alters the kidneys ability to excrete sodium and water
Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;
point 2
- In human essential hypertension and genetic rat models of hypertension kidney function is altered
Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;
point 3
- All effective anti-hypertensive agents studied to date have actions that promote sodium and water excretion
Describe the Evidence for kidney is indeed the long- term controller of arterial pressure control;
point 4
- Transplantation of a hypertensive kidney into a normotensive rat raises arterial pressure and vice versa.
What are the two main causes of renovascular hypertension
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.
What are the experimental models of hyperntesion?
Surgical: - Goldblatt model - 2K-1C Pharmacological - Angiotensin II infusion - DOCA salt - NO blockade Genetic - Dahl Salt senstitive - SSH ALL have impaired renal function
How are pressure diuresis curves formed?
Perfusing a kidney in isolation i.e no nerves of hormones
Describe the pressure diuresis curve;
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
Go through the slides and learn all points with an exclamation mark!
now
What happens to CO if you lose an arm?
It reduces as CO depends on oxygen needed by tissues, and now less tissue
Describe the pressure natriuresis curve comparing chronic and acute homeostasis;
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)
