Hypertension 2013 Pathophysiology

Primary Hypertension
2. Pathophysiology

Prof. Dr. med. Günter Hennersdorf
Germany
SES consultant cardiologist

Pathophysiology of Hypertension

• Primary Hypertension 90%
– Prevalence about 60% (age 60+)
– Prevalence about 15-25% (age 25+)
– Prevalence mean 35%
• Secondary Hypertension 10%
– but: may normalize by special treatment (surgery,
hormone treatment)!

April 2013 ghennersdorf SES FESC DGK


H. without primary organic cause


Mean SBP
Female
Male

Normal course
of blood pressure over age

Mean DBP age

male
female

age

Cardiovascular risk factors
• not modifyable
– Ethnic-genetic risk (black people)
– Age
– Gender
• modifyable
– Hypertension
– Hyperlipidemia (Cholesterol, TGs)
– Smoking
– Diabetes
– Overweight
– Inactivity (physical)
– Stress


Specific hypertension risks
• not modifyable
– Ethnic-genetic risk (black people)
– Age
– Gender
• modifyable
– Diabetes
– Overweight
– Alcohol
– Salt intake
– combination


Prevalence of risk factors
within western populations
(FRAMINGHAM-Trial 1998):

Hypertension 20 %
>65 J.: 65%

Smoking 31 %

Overweight 54 %

Hyperlipidemia 50 - 60 %


Pathophysiology of Hypertension: risks

mortality risk and blood pressure

Factors inducing Hypertension
• Renin-angiotensin system RAS, RAAS
• Sympathetic nervous system
• Insuline resistance
• Overweight
• Stiff vessel walls (endothelial dysfunction)
• Vasoactive substances (NO, Endotheline)
• Kallikrein secretion
• Natriuretic peptides


Factors inducing Hypertension
• Neurohumoral system dysbalance
– Renin-angiotensin system RAS, RAAS
– Sympathetic nervous system

Most important hypertension cause!



Heart Rate x Stroke volume

cardiac output x Peripheral resistance = Blood pressure

Basic equation according to
Law of OHM:

Current I x Resistance R = Voltage U


Neuro-humoral Regulation of Hypertension

Heart rate x stroke volume x Peripheral resistance = Blood pressure

alpha1
beta1

Norepinephrine Angiotensin II

Nervous system Humoral RAAS*

*RAAS or RAS: renine angiotensine aldosterone system



The role of endothelium
and the RAAS cascade


prorenine, katecholamines

Angiotensinogene
Renin Pathway of RAAS in the
Pathway of RAAS in the
Organism (kidney, heart, Tissues: e.g.
Angiotensin I
Vessels) to maintain Vessel wall
Fluid volume control, ACE
Adjustment of CO and
Resistance. Angiotensin II Competition of receptors:
If regulation fails, high AT1 vasoconstriction
AT2 vasodilatation
blood pressure occurs

receptor

AT1 AT2

Pathophysiology of Hypertension:
Angiotensin II Stimulation
Sodium, renine

Kidney

Ang II* *Ang II effects mediated by AT1

Hypophysis Adrenal gland

Hormone release Aldosterone, katecholamines


Angiotensin II Effects

synaptic conduction
Brain

vasoconstriction

vessels Ang II Heart hypertrophy

constriction

AT1 mediated effects of Uterus contraction
Angiotensin II



basic structure and contents of the vessel intima
endothelium
Contents
Smooth muscle cells
intima SMC SMC
media Collagenes
Thrombocytes
Outer layer Ox-LDL
NO
Kinines
Enzymes
coagulation factors
platelet activation factors
thromboxane
April 2013 prostacycline
ghennersdorf SES FESC DGK

ACh
Vasoconstriction Vasodilatation

NE Vessel dilatation;
NE endothelium intact
NE

ACh

NE
NE=Norepinephine
Ach=Acetylcholine NE

NE no dilatation;
endothelium removed
Furchgott‘s basic experiment (1980): key role of endothelium


platelets

growth factors

Endothelial dysfunction causing atherosclerosis and vasoconstriction, infarction

Angiotensin II Actions
on endothelium and
NO =nitric oxide

AT1 AT2

AT1 stimulation AT2 stimulation
leads to: leads to:
growth+
vasoconstriction differentiation
vasodilatation
vasoactivity
NO inhibition NO
Smooth muscle cell
growth

April 2013 ghennersdorf SES FESC DGK modified acc. to Unger T et al 1996


constriction

vascular resistance

Endothelial dysfunction causing hypertension



n.sympathicus RAAS*

Stress Genetic/Familial Vasoconstriction
social ethnic
familial Hereditary Endothelial
salt sensitivity dysfunction
*renine angiotensine aldosterone system



Conclusion:
Conclusion:
is a target disease mainly
is a target disease mainly
of the RAAS -- intima -- endothelium system!
of the RAAS intima endothelium system!

the endothelium is the major player



time course of hypertension development
no symptoms Nonspecific Symptoms:
Head ache,
Palpitation,
Onset,Trigger Chronic stage Exertional dyspnea target organ damage death

3 4 5 6 6+ (x10th years)

accelerated course


Trigger example: Obesity, Hyperinsulinism, Type-2-
Diabetes

Hypertension

Metabolic syndrome (X)




AT2 -
beta1 + (NO )
AT1 +
alpha1
Norepinephrine Angiotensin II Hyperinsulinemia

Sympathicus RAAS



Target organ damage
followed by
arterial hypertension



• Target organ damage:
– Brain: Stroke (ischemic, hemorrhagic)
– Heart: CAD, Heart failure (mainly diastolic)
– Vessels:
• Peripheral arterial disease
• Central arterial disease: aortic dissection, aneurysm
• Renovascular disease


Typical target organ damages following arterial hypertension

CAD

stroke

LV hypertrophy

Peripheral artery disease:
necrosis, gangrene



Left ventricular
hypertrophy
Coronary Atherosclerosis
Heart failure
(prevalence ~50%)

Main target lesions

Brain: Stroke
(prevalence ~20%)
Wall damage
Cerebral Atherosclerosis

Renovascular damage



Left ventricular hypertrophy remodeling
(w. anterior wall infarction) Heart failure


Heart failure and hypertension

Diastolic Heart failure: stiffness and relaxation disturbances

u

normal Early stage Late stage
Ultrasound appearance of mitral flow patterns (EA relation)



Survival rate in relation to renal damage (by renal albuminuria)

Survival rate% Alb. < median
Alb. > median

Median 7,52 µg/min
P=0,0078



Secondary Hypertension
H. with primary organic cause


secondary H.

• Renal 5%
– Parenchymal
– Renovascular (0,3%) (corrected to normal by balloon treatment or surgery!)
– Tumors
– Little‘s disease
• Endocrine
– Thyroid dysfunction (1%)
– Adrenal (0,3%)
– Carcinoid
– hormones
• Aortic coarctation
• Pregnancy
• Neurogenic (brain tumor, lead, porphyria, sleep apnea)
• Acute stress (including surgery)
• iv. volume increase
• Alcohol abuse

Some may induce primary hypertension, so that the relationships sometimes are weak


Systolic Hypertension
(H. of the aged w. or w/o. diastolic lowering


Pathophysiology of Hypertension: Isolated
systolic Hypertension (ISH).

• Rigidity of the aorta (aged aorta)
• Increased cardiac output
– Aortic Valve regurgitation
– AV fistula
– Thyreotoxic crisis
– Paget‘s disease (bone vessel fistulas)
– Beriberi (Vit. B deficiency)
– Hyperkinetic circulation (young, unfit)


Definition of arterial Hypertension AH*
systolic blood pressure diastolic blood pressure

Normal <140 and <90
(diabetic <130 <80)
mild AH 140-179 and/or
90-104
borderline AH 140-159 90-94
intermediate >=180 and/or >=105
severe AH
isolated >=160 and <90
systolic AH 140-159
(ISH)
April 2013 ghennersdorf SES FESC DGK *WHO 2000

Systolic Hypertension.


Systolic Hypertension (SAH).

• Risk of SAH in the elderly (SHEP, SYST-EUR Trials)

– Stroke 20% Reduction)
– Heart failure 54% Reduction)
– Death 24%

These results were maintained over 5 years observation


Pathophysiology of Hypertension: Morning
Hypertension.

Blood pressure

Heart rate
Resistance
Cardiac output
Renal function


Increased cardiovascular morning risk
Increased cardiovascular morning risk
Morning BP rise
Stroke /2h
Infarction /1 h

6 pm 0:00 6 am 12 am


diastolic blood pressure DBP
Prognosis
Stroke risk and DBP CAD risk and DBP

4,0 4,0

2,0

1,0 1,0

76 84 91 98 105 76 84 91 98 105



understand
Save lives and improve life quality

diagnose

treat

control


Cardiovascular Diseases
Hypertension Management
part I
The End

Hypertension 2013 Pathophysiology

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