Role of the Kidney in Long Term Role of the Kidney in Long Term Regulation of Arterial PressureRegulation of Arterial Pressure

M. Rasjad IndraM. Rasjad IndraLab. of PhysiologyLab. of Physiology

University of BrawijayaUniversity of Brawijaya

Renal-Body Fluid System for Renal-Body Fluid System for Arterial Pressure ControlArterial 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 Two Determinants of Long-Term Arterial Pressure LevelPressure Level

00

2

4

6

8

50 100 150 200 250

Normal

ElevatedPressure

ElevatedPressureIn

take

or O

utpu

t ( x

N

orm

al )

Arterial Pressure ( mm Hg )

Renal output of water & salt

Water and salt intake

How Does Increased Fluid Volume Elevate How Does Increased Fluid Volume Elevate the Arterial Pressure?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 Importance of Salt in the Renal-Body Fluid Schema for Arterial Pressure RegulationSchema for Arterial Pressure Regulation

Excess salt in the body Excess salt in the body → The osmolality of the → The osmolality of the body fluid increases → Stimulate the thirst body fluid increases → Stimulate the thirst center → Drink extra amounts of water → center → Drink extra amounts of water → Increases the extra-cellular fluid volumeIncreases the extra-cellular fluid volumeThe increase in osmolality in the extracellular The increase in osmolality in the extracellular fluid → Stimulate hypothalamus to secrete ADH fluid → Stimulate hypothalamus to secrete ADH → The kidney reabsorb water from the renal → The kidney reabsorb water from the renal tubular fluid → Increasing the extracellular fluid tubular fluid → Increasing the extracellular fluid volume.volume.Increasing extracellular volume → Elevation of Increasing extracellular volume → Elevation of the arterial pressure.the arterial pressure.

HypertensionHypertensionIt’s often caused by excess extra-cellular It’s often caused by excess extra-cellular fluid volumefluid volumeMAP is greater than the upper range of the MAP is greater than the upper range of the accepted normal measure (> 110 mm Hg).accepted normal measure (> 110 mm Hg).– Diastolic pressure > 90 mm HgDiastolic pressure > 90 mm Hg– Systolic pressure > 135 mm HgSystolic pressure > 135 mm HgSevere hypertension: MAP 150 – 170 mm Severe hypertension: MAP 150 – 170 mm HgHg– Diastolic pressure : 130 mm HgDiastolic pressure : 130 mm Hg– Systolic pressure : 250 mm HgSystolic pressure : 250 mm Hg

The lethal effects of hypertensionThe lethal effects of hypertension

1.1. Excess workload on the heartExcess workload on the heart– Early heart failureEarly heart failure– Coronary heart diseaseCoronary heart disease

2.2. Ruptures a major blood vessel in the Ruptures a major blood vessel in the brain (stroke)brain (stroke)

ParalysisParalysisDementiaDementiaBlindnessBlindness

3.3. Multiple hemorrhages in the kidneysMultiple hemorrhages in the kidneysKidney failueKidney failueUremiaUremia

Volume-Loading Hypertension Caused by Reduced Volume-Loading Hypertension Caused by Reduced Renal Mass Along with Simultaneous Increase in Salt Renal Mass Along with Simultaneous Increase in Salt

Intake Intake

090

100

110

120

130

140

150

10 20 30 40 50 60 70 80

0.9% NaCl Tap water 0.9% NaCl

70 % of renal tissue removed

Mea

n ar

teria

l pre

ssur

e (p

er c

ent o

f co

ntro

l)

Days

Two separate sequential stages of Two separate sequential stages of volume-loading hypertensionvolume-loading hypertension

1.1. First stage:First stage:Fluid volumeFluid volume↑ → Cardiac output ↑ → High ↑ → Cardiac output ↑ → High blood pressureblood pressure

2.2. Second stage:Second stage:High blood pressure → Total peripheral High blood pressure → Total peripheral resistance ↑ → the cardiac output so near to resistance ↑ → the cardiac output so near to normalnormal

Renin-Angiotensin SystemRenin-Angiotensin System

Renin:Renin:– Small protein EnzymeSmall protein Enzyme– Synthesized in the JG cellsSynthesized in the JG cells– Stored in an inactive form: Stored in an inactive form: ProreninProrenin– This secretion is stimulated by fall blood This secretion is stimulated by fall blood

pressurepressure– Catalyze reaction: Angiotensinogen Catalyze reaction: Angiotensinogen → →

Angiotensin I.Angiotensin I.– It persists in the blood for 30 – 60 minutes.It persists in the blood for 30 – 60 minutes.

Decreased arterial pressure

Kidney

Angiotensinogen

Renin

Angiotensin I

Liver

Converting enzyme

Lungs

Angiotensin II

Blood vessels

Vasoconstriction

Aldosteron secre.

Sodium reabsorption

H2O & Na reabsorption

ADH secretion

Renal retension H2O & Na

Normal effective arterial blood volume

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

0 4 8 12

0

1

7

50

100

150

200

Systemic arterial pressure

Distal renal artery pressure

Renin secretion

Renal artery constricted

Constriction releasedPr

essu

re (m

m

Hg)

Tim

es

norm

al

Days

Other Types of HypertensionOther Types of Hypertension

1.1. Hypertension caused by Coarctation AortaHypertension caused by Coarctation AortaBlockage proximal to the kidney branchesBlockage proximal to the kidney branchesThe arterial pressure in the lower body usually The arterial pressure in the lower body usually normal & in the upper body is far higher than normal & in the upper body is far higher than normalnormal

2.2. Hypertension in Toxemia GravidarumHypertension in Toxemia Gravidarum Thickening of the kidney glomerular membrane Thickening of the kidney glomerular membrane

(autoimmune process?)(autoimmune process?)3.3. Neurogenic HypertensionNeurogenic Hypertension

Strong stimulation of the sympathetic nervous Strong stimulation of the sympathetic nervous systemsystem

Excited Excited AnxietyAnxiety

Essential HypertensionEssential HypertensionAbout 90-95 % of hypertension casesAbout 90-95 % of hypertension casesUnknown origin & strong hereditary tendencyUnknown origin & strong hereditary tendencyCharacteristics of severe essential hypertension:Characteristics of severe essential hypertension:

1.1. MAP is increased 40 – 60 %.MAP is increased 40 – 60 %.2.2. In the late & more severe stages: RBF decreased 50 %In the late & more severe stages: RBF decreased 50 %3.3. The resistance to blood flow through the kidneys is The resistance to blood flow through the kidneys is

increased twofold to fourfold.increased twofold to fourfold.4.4. But, GFR is often near normal.But, GFR is often near normal.5.5. The cardiac output is about normal.The cardiac output is about normal.6.6. The TPR is increased about 40 – 60 % The TPR is increased about 40 – 60 % ~ elevation of ~ elevation of

arterial pressure.arterial pressure.7.7. The kidney will not excrete adequate amount of salt The kidney will not excrete adequate amount of salt

and water unless the arterial pressure is high.and water unless the arterial pressure is high.

00

1

2

3

4

5

6

50 100 150

Salt

inta

ke a

nd o

utpu

t (tim

es n

orm

al)

Arterial pressure (mm Hg)

Normal intake

High intake

Normal Essential hypertension

Nonsalt-sensitive

Salt-sensitive

B1E B

A

C

D

Treatment of Essential HypertensionTreatment of Essential HypertensionTwo types of drugs:Two types of drugs:

1.1. Increase renal blood flow (vasodilator drug):Increase renal blood flow (vasodilator drug):1.1. Inhibiting sympathetic nervous signal to the Inhibiting sympathetic nervous signal to the

kidneys or blocking the action of the sympathetic kidneys or blocking the action of the sympathetic transmitter substance on the renal vasculaturetransmitter substance on the renal vasculature

2.2. Directly paralyzing the smooth muscle of the Directly paralyzing the smooth muscle of the renal vasculaturerenal vasculature

3.3. Blocking the action of the renin-angiotensin Blocking the action of the renin-angiotensin system on the renal vasculature or renal tubules.system on the renal vasculature or renal tubules.

2.2. Decrease tubular reabsorption of salt and Decrease tubular reabsorption of salt and water:water:

– NatriureticNatriuretic– DiureticDiuretic

0 30 1 2 4 8 16 32 1 2 4 8 16 1 2 4 8 16

Detik Menit Jam Hari

0

1

2

3

4

5

6

7

8

9

10

11

Baroreseptor

Kemoreseptor

CNS ischemic responseRenal-blood volume pressure control

Stress relaxation

Renin-angiotensin Capillary fluid shift

Aldosterone