Download Pathophysiology of hypertension

Pathophysiology
of Hypertension
Tatár M.
Dept. of Pathophysiology
Jessenius Med. School
- venous return
- extracellular fluid volume
- myocardial contractility
- vasoactive substances
- thickening of arteriolar
wall
Essential Hypertension
• Hemodynamic effect of hormonal, neural and renal
dysregulation of blood pressure
• Pathogenesis is probably a slow and gradual process
• No single or specific cause
• Initiating factors may no longer be apparent when
hypertension is developed, since they have been
„normalised“ by the compensatory interactions
• Initial phase:  cardiac output
• Late phase:  peripheral arteriolar resistance,
cardiac output is normalised
INCREASED EXTRACELLULAR FLUID VOLUME
INCREASED BLOOD VOLUME
INCREASED VENOUS RETURN
INCREASED CARDIAC OUTPUT
AUTOREGULATION
INCREASED TOTAL
PERIPHERAL RESISTANCE
INCREASED BLOOD PRESSURE
Mechanisms of EH
•  activity of renin-angiotensin-aldosteron
• Hyperfunction of sympathetic system
• Vasoactive substances - endothelial dysfunction
• Insulin resistance  obesity
• Arteriolar hypertrophy
• Renal defect to excrete sodium
Increased R-A-A activity
ANGIOTENSINOGENE
J-G
RENIN
ANGIOTENSIN I
ACE
VASOCONSTRICTION
ANGIOTENSIN II
ALDOSTERON
Na+ RETENTION
negative feed back
BLOOD PRESSURE
Tissue R-A system
(Beevers et al., 2001)
- catecholamine and endothelin release
- induction of hypertrophy of smooth muscle cells,
cardiomyocytes
Hyperfunction of sympathetic system
• Primary  activity of
vasomotor neurons
• Angiotensin II and
endothelin increases
activity of vasomotor
neurons
• Norepinephrine potentiates
renin releasing
Vacoactive substances
Influence on vascular tone and sodium transport
Endothelin
Digitalis (ouabain) – like substance
Natriuretic peptides
Sodium transport across vascular smooth muscle
cell membrane
•
Sodium retention  activation
of natriuretic mechanisms
•
Digitalis - like inhibitor of
Na+,K+,ATP-ase
INSULIN
RESISTANCE
 HDL
HYPERINSULINEMIA
SYNDROME X
HYPERTENSION
OBESITY
 VLDL
GLUCOSE
INTOLERANCE
INSULIN
RESISTANCE
 SYMPATHETIC
ACTIVITY
HYPERINSULINEMIA
SODIUM
RETENTION
HYPERTENSION
ARTERIOLAR
HYPERTROPHY
(tonic
activity)
Regulatory cells
(Reaven et al., 1996)
Hypertrophy of Arteriolar Wall
OBESITY
STRESS
Na+ RETENTION
RENAL
HYPOPERFUSION
INSULIN
CATECHOLAMINES
NATRIURETIC
HORMON
ANGIOTENSIN
PRESSURE-GROWTH
EFFECTS
 INTRACELLULAR Ca2+
SMOOTH MUSCLE
CONTRACTION
 Na+/H+ EXCHANGE
VASCULAR WALL
HYPERTROPHY
 PERIPHERAL VASCULAR
RESISTANCE
(Brown, 1997)
Role of Kidneys
(Johnson et al., 2002)
Renal Lesions
1st phase
- normal kydneys and sodium excretion
- sympathetic hyperactivity, R-A stimulation

renal vasoconstriction
2nd phase
- tubular ischemia - interstitial inflammation  ultrafiltration and  Na+ reabsorbtion

increased blood pressure
3rd phase
- elimination of tubular ischemia;
sodium excretion is normal
BP is more increased after enhanced salt intake
Right shift of „pressure-natriuretic“ line
(Cowley and Roman, 1996)
Conclusions
• Interaction between increased activity of sympatihetic and RA systems and dysregulation of sodium balance and
intravascular volume
• Endothelial dysfunction – dysbalance between
vasoconstrictor and vasodilator agents
• Hyperinsulinemia – a) direct effect on sodium retention,
b) sympathetic activation through the suppression of
regulatory neurons in hypothalamus
• Hypertrophy of arteriolar wall – increased vasoconstrictor
reactivity
• Genetic factors: dysfunction of membrane mechanisms of
vascular smooth muscle cells; disorder of sodium exchange
in nephron epithelial cells
• Acquired renal injury: sodium intake is excreted only with
increased blood pressure