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THE ROLE OF RENAL IN
BLOOD PRESSUREREGULATION AND
HYPERTENSION
Umar Zein
Medical Faculty
Prima Indonesia University
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Renal Function:
Excretory
Regulatory
Endocrine
Excretory Function:
Metabolic
GlomerularGlomerular Filtration Rate (GFR)
Creatinin Clearance.
UxV/P ml/min
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Retinopathy
Heart diseases
Stroke or TIA
Nephropathy,Proteinuria, CrCl
Peripheral arterial Disease(atherosclerotic plaqueiliac,carotid, femoral artery,aorta)
Sequelae of Hypertension
Complications of HTN
Cardiac
CNS
Vascular
Retinal
Renal
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Patho-physiology of Hypertension
HTN develop gradually over a long period of time.
The development of HTN requires the adjustment of
several compensatory mechanisms over time.
Several hypothesis exists for the original
pathogenesis of HTN:
Excess Na intake
Renal Na retention
Renal Angiotensin System (RAS)
Stress & sympathetic over activity
Peripheral resistance
cell membrane and endothelial dysfunction
Obesity
insulin resistance
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Regulation of aldosterone secretion
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Componentsof renin-angiotensin-aldosteronesystem
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Action of aldosterone on the renal tubule.
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Excess Na
intake
Reduced
NephronNumbers
Stress
Genetic
Alterations Obesity
Endothelium
derivedfactors
Renal Na
retention
Decreased
filtration
surface
Sympatheic
Over activity
RAS
Excess
Cell-membrane
alterations
Hyper
insulinemia
FluidVolume
Venous
constriction
Preload Contractibility Functionalconstriction
Structuralhypertrophy
Blood pressure=HTN
Cardiac Output Peripheral ResistanceXand/or
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Pathophysiology of blood pressure
changes
BLOODPRESSURE
CARDIAC
OUTPUT
PERIPHERAL
RESISTANCE
BLOOD VOLUME
CONTRACTILITY
PULSE RATESTRUCTURAL HYPERTROPHY
FUNCTIONAL
VASOCONSTRICTION
Normal Remodeling
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Pressure-natriuresis Relation in Arterial
Hypertension
Blood pressure
NatriuresisNormotensives
Hypertensives
Guyton, 1972
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Activity of the Autonomic Nervous System in
Hypertension
Heart
Vessels
Smooth muscle cells
membrane activity
Kidney
Pulse ratecontractility
Increased resistance
Sodium retention
vasoconstriction
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Renin-Angiotensin SystemThe Damaging Effects of
Angiotensin II
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Renin-Angiotensin System
Angiotensinogen
Angiotensin I
Angiotensin II
Renin
ACEChymase
tPACatepsin
AT1-R AT2-R ?
Bradykinin
Inactive quinines
B1-R
B2-R
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A-II
Vasoconstriction
Cell Growth
Cell Proliferation
Anti-Natriuresis
Vasodilation?
Inhibition of Cell Growth
Cell Differentiation
Apoptosis
Natruiresis
DIFFERENTIAL EFFECTS OF ANGIOTENSIN RECEPTORS
Production:-aldosterone, endothelin,catecholamines, PAI-1adhesion molecules,growth factors
Production :-Nitric Oxide
AT1
ANG IIAT2
ANG II
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Effects of angiotensin II
Peripheral
vasoconstriction
Vascular
proliferation
Adrenergicactivity
Renin
secretion
Aldosterone
secretion
Thirst
mechanism
Water and sodium retention
Efferent arteriole
vasoconstriction
AII
AT1-R
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Bradykinin and Endothelins
Bradykinin
B1-R B2-RETA-RTB-R
Proendothelins
ET1 ET2 ET3
Endothelial Cell
Nitric Oxide
Smooth Muscle Cell
Vasoconstrictionvasodilatation
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Nitric Oxide (NO)L-arginine
NO
O 2- Nitrogenated
Heam-proteins
cGMP
eNOS
oxidases
NO
Peripheralvasoconstriction
Renalresistance
Glomerulo-tubular
Feedback
Renin Secretion
SodiumReabsorption
Pressure-
natriuresis