1. Long Term Regulation of Arterial Blood Pressure and Hypertension
Balance Between Fluid Intake and Output

2. Pressure Natriuresis. Arterial pressure is a signal for regulation of NaCl excretion.
arterial pressure   NaCl reabsorbed in the proximal tubule  more NaCl to the macula densa  TGF  autoregulation RBF, GFR.
Pressure natriuresis can normalize BP by decreasing the effective circulating volume – this response connects BP and ECFV.

3. Renal-Body Fluid System for Arterial Pressure Control
When the body contains too much extracellular fluid, the blood volume and arterial pressure rise
Pressure Diuresis and Pressure Natriuresis
At high pressure, the kidneys excretes the excess volume into urine and relieves the pressure
At low pressure, the kidney excretes far less fluid than is ingested

4. Renal Urinary Output Curve
or Renal function curve

5. Pressure Control by Renal-Body Fluid Mechanism
Over the long period, water and salt output must equal intake
Equlibrium point
Return of the arterial pressure always exactly back to the equlibrium point in the “infinite feedback gain” principle

6. Two Determinants of Long-Term Arterial Pressure Level
The degree of pressure shift of the renal output curve for water and salt
The level of water and salt intake line
It is impossible to change the long-term mAP level to a new value without changing one or both of the two basic determinants of long-term AP

7. Two Determinants of Long-Term Arterial Pressure Level

8. Failure of increased TPR to elevate the long-term level of AP if fluid intake and renal function do not change
AP = Cardiac output x Total Peripheral Resistance
So, increase in TPR should elevate AP
But this acute rise in AP is not maintained if the kidneys function properly
Why?
Pressure diuresis and pressure natriuresis

9. Failure of increased TPR to elevate the long-term level of AP if fluid intake and renal function do not change

10. Increased Fluid Volume Can Elevate AP by Increasing Cardiac Output or Total Peripheral Resistance

11. Importance of salt (NaCl) in the renal-body fluid diagram for arterial pressure regulation
An increase in salt is far more likely to elevate AP than is an increase in water intake
Water can be eliminated easily, but salt not
Accummulation of salt in the body
Stimulation of thirst center in the brain
Increased osmotic pressure stimulates release of vasopressin (ADH)

12. Hypertension
“Hypertension is defined as sustained abnormal elevation of the arterial blood pressure”

13. Hypertension STROKE HEART FAILURE ATHEROSCLEROSIS
Leads to wear and tear
is a major risk factor for cardiovascular diseases such as:
STROKE
HEART FAILURE
ATHEROSCLEROSIS
30% of world’s deaths

14. Complications Complications as a result of hypertension include:
Stroke
Dementia
Myocardial Infarction
Congestive Heart Failure
Retinal Vasculopathy
Renal Disease or Failure
Slide #18:
Untreated, resistant or uncontrolled hypertension can result in these complications. Mild hypertension left untreated can progress into severe or malignant hypertension. Hypertension is usually asymptomatic until it reaches severe stages (Brashers, 2006).

15. Chronic Hypertension is Caused by Impaired Renal Function
Mean Arterial Pressure > 110 mmHg (normal is about 90 mmHg)
Systolic >140, diastolic >90 mmHg
Hypertension can be lethal
Heart failure
Damage of a large vessel in the brain (cerebral infarct or stroke)
Kidney failure
Volume-loading hypertension means hypertension caused by excess accumulation of extracellular fluid in the body

16. Volume-loading hypertension
Reduced renal mass and increased salt intake

17. Volume-loading hypertension: Two separate sequential stages
The first stage: increased fluid volume causing increased cardiac output  hypertension
The second stage: High blood pressure, high TPR but return of the cardiac output near the normal
Hypertension
Marked increase in TPR
Almost complete return of the extracellular fluid volume blood volume and cardiac output back to normal
Volume-loading hypertension in patients who have no kidneys and need for dialysis

18. Hypertension caused by primary Aldosteronism
Another type of volume-loading hypertension is caused by excess aldosterone in the body – (other steroids)
A small tumor of adrenal glands and primary aldosteronism
Aldesteron increases reabsorbtion of salt and water  increased blood volume and reduced urine output
Consequently, hypertension develops

19. The Renin-Angiotensin System Pressure control and Hypertension
Renin is an enzyme released by the kidneys when the arterial pressure falls too low
It is synthesized and stored in inactive form called prorenin in juxtaglomerular cells
JG cells are modified smooth muscle cells in the walls of afferent arterioles
Renin acts on angiotensinogen (a plasma globulin)
Half life of renin is about 30 mins
Angiotensin I, converting enzyme and Angiotensin II

20. The Renin-Angiotensin System Pressure control and Hypertension

21. Rapidity and Intensity of Vasoconstrictor Pressure Response to the Renin-Angiotensin System
Renin-angiotensin vasoconstrictor system requires about 20 mins to become fully active

22. Effect of Angiotensin in the Kidneys to Cause Renal Retention of Salt and Water
Angiotensin acts directly on the kidneys to cause salt and water retention
Makes the kidneys retain salt and water
Causes vasoconstriction in renal arteries
Angiotensin causes the adrenal gland to secrete aldosterone
- Aldosterone increases salt and water retention by the kidneys

23. Role of Renin-Angiotensin System in Maintaining a Normal Arterial Pressure Despite Wide Variations in Salt Intake
When the renin-angiotensin system functions normally, pressure rises no more than 4 to 6 mmHg in response to as much as a 50-fold increase in salt intake

25. Other Types of Hypertension Caused by Combinations of Volume-Loading and Vasoconstriction
Aort Coarctation – hypertension
High BP in the upper body, but BP is normal in the lower body
Autoregulation of hypertension

26. Coarctation of the Aorta
Coarctation usually occurs just distal to the left subclavian artery at the ligamentum arteriosum
May also occur just proximal to the left subclavian.
Causes systemic hypertension and secondary LVH with heart failure.

27. Other Types of Hypertension Caused by Combinations of Volume-Loading and Vasoconstriction
Hypertension in pre-eclampsia (toxemia of pregnancy)
Ischemia of the placenta and subsequent release of toxic factors causing hypertension
Endothelial dysfunction – reduction of Nitric Oxide
Impaired renal pressure natriuresis
Development of hypertension
Thickening of the kidney glomerular membranes (auotoimmune process)

28. Other Types of Hypertension Caused by Combinations of Volume-Loading and Vasoconstriction
Neurogenic Hypertension
Acute neurogenic hypertension can be caused by strong stimulation of the sympathetic nervous system
Excitement, anxiety induces sympathetic activity which causes peripheral vasoconstriction and acute hypertension occurs
Acute neurogenic hypertension caused by sectioning the baroreceptor nerves

29. Primary (Essential) Hypertension
90 to 95% of hypertension cases are of primary
It is of unknown origin
Genetics: there is a strong hereditary tendency
Environment: Excess weight and sedentary life style
Neurohormonal mediators

30. Some Characteristics of Primary Hypertension
Cardiac output is increased due to additional blood flow required for the extra adipose tissue and increased metabolism
Sympathetic nerve activity (especially in kidneys) is increased in OW patients (leptin – vasomotor center ?)
Angiotensin II and aldosterone are increased (sympathetic stimulation-renin-aldosterone …)
Renal-pressure natriuresis mechanism is impaired
If hypertension is not treated, there may also be vascular damage in the kidney that can reduce glomerular filtration rate

31. Graphical Analyses of AP Controling Primary Hypertension
Reason for the difference between non-salt and salt-sensitive hypertension is probably related to structural and functional differences in kidney (nephrons..)

32. Treatment of Primary Hypertension
Two general classes of drugs are used
Vasodilator drugs that increase renal blood flow
Natriuretic and diuretic drugs that decrease tubular reabsorption of Na and water
Vasodilator drugs
Inhibiting sympathetic nerve activity to kidneys
Direct relaxation of smooth muscle of renal vasculature
Blocking the action of renin-angiotensin system on renal vasculature or tubules

33. Summary for Arterial Pressure Regulation
AP is regulated not by a single pressure controlling system (several inter-related systems)
To achieve
Survival
Returning the blood volume and pressure back to normal
Mechanisms
Rapidly acting pressure control mechanisms
Intermediate mechanisms that act after several minutes – hours
Long-term arterial pressure regulation

34. Summary for Arterial Pressure Regulation

35. Intermediate mechanisms that act after several minutes – hours
Renin-Angiotensin vasoconstrictor mechanism
Stress-relaxation of the vasculature
Shift of fluid through capillary walls in and out of circulation
* These mechanisms become mostly activated within 30 mins to several hours

36. Long term mechanisms for AP regulation
Role of the kidneys
Many factors can affect pressure-regulating level of the renal-body fluid mechanism
Aldosterone
Renin-Angiotensin system
Nervous system (increased sympathetic activity)