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


Primary HypertensionH. without primary organic cause


Pathophysiology of HypertensionMean SBP

age

ageMean DBP

Normal courseof blood pressure over age

FemaleMale

male

female


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 factorswithin 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!



cardiac output x Peripheral resistance = Blood pressure

Basic equation according toLaw of OHM:

Current I Resistance R Voltage Ux =

Heart Rate Stroke volumex


Neuro-humoral Regulation of Hypertension

Heart rate x stroke volume x Peripheral resistance = Blood pressure

*RAAS or RAS: renine angiotensine aldosterone system

Nervous system

Norepinephrine

alpha1beta1

Humoral RAAS*

Angiotensin II



The role of endotheliumand the RAAS cascade



Angiotensinogene

Angiotensin I

Angiotensin II

receptor

Renin

ACE

AT1 AT2

prorenine, katecholamines

Pathway of RAAS in theOrganism (kidney, heart,Vessels) to maintain Fluid volume control,Adjustment of CO and Resistance.If regulation fails, high blood pressure occurs

Pathway of RAAS in theTissues: e.g.

Vessel wall

Competition of receptors:AT1 vasoconstriction AT2 vasodilatation


Hypophysis Adrenal gland

Kidney

Ang II*

Hormone release

Pathophysiology of Hypertension:Angiotensin II Stimulation

Sodium, renine

Aldosterone, katecholamines


*Ang II effects mediated by AT1

vessels

Uterus

Heart

Brain

Ang II

Pathophysiology of Hypertension: Angiotensin II Effects

AT1 mediated effects of Angiotensin II

synaptic conduction

hypertrophy

contraction

constriction

vasoconstriction



ContentsSmooth muscle cells SMCCollagenesThrombocytesOx-LDLNOKininesEnzymescoagulation factorsplatelet activation factorsthromboxaneprostacycline

intima

media

Outer layer

basic structure and contents of the vessel intima

endothelium

SMC



NE

NE

NE

ACh

NE

NE

NE

ACh

Vessel dilatation; endothelium intact

no dilatation; endothelium removed

Furchgott‘s basic experiment (1980): key role of endothelium

NE=NorepinephineAch=Acetylcholine


Vasoconstriction Vasodilatation


platelets

growth factors

Endothelial dysfunction causing atherosclerosis and vasoconstriction, infarctionApril 2013 ghennersdorf SES FESC DGK

ATAT11 ATAT22

ATAT11 stimulation stimulation

leads to:leads to:

growth+growth+

vasoconstrictionvasoconstriction

ATAT2 2 stimulation stimulation

leads to:leads to:

differentiationdifferentiation

vasodilatationvasodilatation vasoactivityvasoactivity

Smooth muscle cell Smooth muscle cell growthgrowth

Angiotensin II Actions Angiotensin II Actions on endothelium and on endothelium and

NO =nitric oxideNO =nitric oxide

modified acc. to Unger T et al 1996

NONO inhibition



Endothelial dysfunction causing hypertension

constriction

vascular resistance


Genetic/Familial


n.sympathicus RAAS*


Stress Vasoconstriction

*renine angiotensine aldosterone system

socialfamilial

ethnicHereditarysalt sensitivity

Endothelialdysfunction



Conclusion:Primary Hypertension

is a target disease mainlyof the RAAS - intima - endothelium system!

Conclusion:Primary Hypertension

is a target disease mainlyof the RAAS - intima - endothelium system!

the endothelium is the major player



time course of hypertension development

Onset,Trigger Chronic stage

Nonspecific Symptoms:Head ache,Palpitation,Exertional dyspnea target organ damage death

3 4 5 6 6+(x10th years)

accelerated courseApril 2013 ghennersdorf SES FESC DGK

no symptoms


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

Hypertension

Metabolic syndrome (X)




Sympathicus

Norepinephrine

alpha1

beta1

RAAS

Angiotensin II

AT1 +

AT2 -

Hyperinsulinemia

+ (NO )



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


LV hypertrophy

CAD

Peripheral artery disease:necrosis, gangrene

stroke


Main target lesions

Heart failure(prevalence ~50%)

Brain: Stroke(prevalence ~20%)

Wall damageCerebral Atherosclerosis

Left ventricularhypertrophyCoronary Atherosclerosis

Renovascular damage



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


remodeling

u

Heart failure and hypertension

Diastolic Heart failure: stiffness and relaxation disturbances

normal Early stage Late stage


Ultrasound appearance of mitral flow patterns (EA relation)


Survival rate% Alb. < median

Alb. > median

Median 7,52 µg/minP=0,0078

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



Secondary HypertensionH. with primary organic cause


Pathophysiology of Hypertension: 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)


*WHO 2000

Definition of arterial Hypertension AH*systolic blood pressure

diastolic blood pressure

Normal(diabetic

<140<130

<90<80)

mild AHborderline AH

140-179140-159

90-10490-94

intermediate severe AH

>=180 >=105

isolated systolic AH (ISH)

>=160140-159

<90

and

and/or

and/or

and


Pathophysiology of Hypertension: Systolic Hypertension.


Pathophysiology of Hypertension: Systolic Hypertension.


http://www.hypertensiononline.org/slides2/slide01.cfm?q=isolated+systolic+hypertension&pg=2

Pathophysiology of 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 rateResistanceCardiac outputRenal function


Stroke /2h

Infarction /1 h

Morning BP rise

6 pm 0:00 12 am6 am


Increased cardiovascular morning riskIncreased cardiovascular morning risk

Pathophysiology of Hypertension: diastolic blood pressure DBP

Prognosis

1,0

4,0

76 84 91 98 105

Stroke risk and DBP

1,0

4,0

76 84 91 98 105

CAD risk and DBP

2,0



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Cardiovascular DiseasesHypertension Management

part I

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Hypertension 2013 Pathophysiology

Health & Medicine

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