Role of the Kidney in Long Term Regulation of Arterial Pressure

M. Rasjad Indra Lab. of Physiology University of Brawijaya

Renal-Body Fluid System for Arterial Pressure Control

Too much extracellular fluid The blood volume & arterial pressure rise

The kidneys excrete thr excess extracellular fluid

The arterial pressure back toward normal

Pressure diuresis: An increase in arterial pressure only a few mm Hg can double the renal output of water
Pressure natriuresis: An increase in arterial pressure only a few mm Hg can double the renal output of salt

Two Determinants of Long-Term Arterial Pressure Level

8 Renal output of water & salt Intake or Output ( x Normal ) Water and salt intake

6
Elevated Pressure 4

Normal

Elevated Pressure

0 0 50 100 150 200 250 Arterial Pressure ( mm Hg )

How Does Increased Fluid Volume Elevate the Arterial Pressure?

Extracellular fluid volume Blood Volume Mean circulatory Filling pressure Venous return Cardiac output Auto-regulation Total peripheral resistance Arterial pressure

Importance of Salt in the Renal-Body Fluid Schema for Arterial Pressure Regulation
Excess salt in the body The osmolality of the body fluid increases Stimulate the thirst center Drink extra amounts of water Increases the extra-cellular fluid volume The increase in osmolality in the extracellular fluid Stimulate hypothalamus to secrete ADH The kidney reabsorb water from the renal tubular fluid Increasing the extracellular fluid volume. Increasing extracellular volume Elevation of the arterial pressure.

Hypertension
Its often caused by excess extra-cellular fluid volume MAP is greater than the upper range of the accepted normal measure (> 110 mm Hg).
Diastolic pressure > 90 mm Hg Systolic pressure > 135 mm Hg

Severe hypertension: MAP 150 170 mm Hg

Diastolic pressure : 130 mm Hg Systolic pressure : 250 mm Hg

The lethal effects of hypertension

1. Excess workload on the heart Early heart failure Coronary heart disease 2. Ruptures a major blood vessel in the

brain (stroke)
Paralysis Dementia Blindness

3. Multiple hemorrhages in the kidneys Kidney failue Uremia

Volume-Loading Hypertension Caused by Reduced Renal Mass Along with Simultaneous Increase in Salt Intake
70 % of renal tissue removed Mean arterial pressure (per cent of control)
150 140 130 120
0.9% NaCl Tap water 0.9% NaCl

110 100 90 0 10 20 30 40 50 60 70 80

Days

Two separate sequential stages of volume-loading hypertension

1. First stage: Fluid volume Cardiac output High blood pressure 2. Second stage: High blood pressure Total peripheral resistance the cardiac output so near to normal

Renin-Angiotensin System
Renin:
Small protein Enzyme Synthesized in the JG cells Stored in an inactive form: Prorenin This secretion is stimulated by fall blood pressure Catalyze reaction: Angiotensinogen Angiotensin I. It persists in the blood for 30 60 minutes.

Angiotensinogen Kidney Renin Angiotensin I Decreased arterial pressure

Liver

Lungs Converting enzyme

Angiotensin II

Blood vessels

Aldosteron secre.

ADH secretion

Vasoconstriction

Sodium reabsorption

H2O & Na reabsorption

Renal retension H2O & Na

Normal effective arterial blood volume

Goldblatt Hypertension
Hypertension caused by renal artery constriction The early rise in arterial pressure is caused by the Renin-Angiotensin vasoconstrictor mechanism. The second rise in arterial pressure is caused by retention of salt and water by constricted kidney

200

Renal artery constricted

Constriction released

Pressure (mm Hg)

150

Systemic arterial pressure

100

Distal renal artery pressure

50

Times normal

Renin secretion
1 0 0 4 8 12

Days

Other Types of Hypertension

1. Hypertension caused by Coarctation Aorta Blockage proximal to the kidney branches The arterial pressure in the lower body usually normal & in the upper body is far higher than normal 2. Hypertension in Toxemia Gravidarum Thickening of the kidney glomerular membrane (autoimmune process?) 3. Neurogenic Hypertension Strong stimulation of the sympathetic nervous system
Excited Anxiety

Essential Hypertension
About 90-95 % of hypertension cases Unknown origin & strong hereditary tendency Characteristics of severe essential hypertension:
1. MAP is increased 40 60 %. 2. In the late & more severe stages: RBF decreased 50 % 3. The resistance to blood flow through the kidneys is increased twofold to fourfold. 4. But, GFR is often near normal. 5. The cardiac output is about normal. 6. The TPR is increased about 40 60 % ~ elevation of arterial pressure. 7. The kidney will not excrete adequate amount of salt and water unless the arterial pressure is high.

Nonsalt-sensitive
Salt intake and output (times normal) Salt-sensitive
6

High intake

B1

Normal

Essential hypertension

Normal intake
1

D C

50

100 Arterial pressure (mm Hg)

150

Treatment of Essential Hypertension

Two types of drugs:
1. Increase renal blood flow (vasodilator drug):
1. Inhibiting sympathetic nervous signal to the

kidneys or blocking the action of the sympathetic transmitter substance on the renal vasculature 2. Directly paralyzing the smooth muscle of the renal vasculature 3. Blocking the action of the renin-angiotensin system on the renal vasculature or renal tubules.

2. Decrease tubular reabsorption of salt and water:

Natriuretic Diuretic

CNS ischemic response

11 10 9 8 7 6 5 4 3 2 1 0 0 Detik 30 1 2 4 Menit 8 16 32 1 2 4 Jam 8 16 Stress relaxation Kemoreseptor Renin-angiotensin Baroreseptor

Renal-blood volume pressure control

Capillary fluid shift

Aldosterone

4 Hari

16