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Hipertensi

Prof. Dr. HM.Bambang Purwanto, dr. SpPD-KGH, FINASIM


Nephrology Hypertension Division of
Internal Medicine Medical Faculty
Sebelas Maret University of Surakarta

PENDAHULUAN

Faktor risiko mayor :


Coronary Heart Disease (CHD)
Myocard Infarct (MI)
Cerebrovascular Accidents (CVA)
Chronic Kidney Diseases (CKD)
Congestive Heart Failure (CHF)

Risiko menjadi hipertensi > 90%


Reappraisal of European Guidelines on Hypertension Management:
A European Society of Hypertension Task Force Document,
Blood Pressure. 2009; 18: 308347

KLASIFIKASI
JNC 7 Report 2003

WHO/ISH Statement on Management of Hypertension 200

ESH/ESC Guidelines for the Management of Arterial Hypertensio

ETIOLOGI
Primer:
Belum diketahui
(mis:genetik)
Sekunder :
Renal
Adrenal
Faktor Biologi lain
Eksogen

Hypertension and Chronic Renal Disease:


Hemodynamic Abnormalities
Cardiac

Mean BP = Output

Increased Cardiac Output


Intravascular Volume
Glomerular filtration
Sodium excretion
Extracellular Fluid
Renal Nerve Activity
Myocardial Performance
Adrenergic Activity

Total Systemic
Vascular Resistance

Increased
Vasoconstriction
Adrenergic Stimuli
Angiotensin II
Endothelin
Endothelium-derived
Contracting Factors
Thromboxane

*Endothelium-derived
Hyperpolarizing Factors
Textor SC. Atlas of Diseases of the Kidney, 2001.

Decreased
Vasodilation
Prostacyclin
Nitric oxide
EDHF*

Hypertension ; basic mechanism..

Gangguan pada Jantung


Serangan StrokeGangguang Fungsi Ginja

Penyakit Arteri

Patogenesis
Patogenesis Komplikasi
Komplikasi Hipertensi
Hipertensi pada
pada Ginjal
Ginjal
Hipertensi kronis
Merusak autoregulasi ginjal
Permeabilitas kapiler
Proteinuri (mikroalbuminuri)
Hukum Homeostasis
Reabsorbsi protein
oleh sel tubulus berlebihan
(stressor)
Ekspresi sitokin :
Robbin, 2005

TNF Apoptosis, nekrosis


IL1 Plag Ateroskleroris
TGF1Fibrosis

Hypertension
Hypertension Complication
Complication Pathogenesis
Pathogenesis
Chronic hypertension
Endothelial Stressor
Expression
TNF
Apoptosis

Necrosis

IL1

IL6

TGF1

Plaque

HCRP

Fibrosis

Atherosclerosis

Robbin, 2008

Renal
Failure

Coronary
Heart Disease

Cerebral

- Stroke
- Dementia
- Parkinson

Appetite

KAKHEKTIN

Hypotalamus

CHACECTIC (THIN)

PG2

FEVER

+ ILI
Aspirin

(Endogenic Pyrogen)

Serum Amyloid

Hepatosit

Fibrinogen

Syntase
ILI
IL6

CRP

Vasopressor receptors
Proteolitic

TNF

Chachexia

Fat Cells
Endhotel
Tissue Factor

Contraction
Vascular smooth muscle cells
Heart
Vasodilatation
Shock

Strong Activation

Trombo Modulin
Shringking

Permeability

Coagulation

Exudation
Inflammation cells
Congestion

Protealitic
Membrane Receptor Disruption
(Brata Widjaya, 2009; Bambang P, 2010)

Eritropoietin Receptor Disruption

Anemia

RISIKO KARDIOVASKULER DAN


DISFUNGSI ENDOTHEL
TNF- Hipertensi Angiotensin II Merokok
Endothelin

Homosistein

PDGF

Diabetes
Natrium

oxLDL
ENZIM NADPH OKSIDASE

Stres Oksidatif
Anti Oksidan

Bradikinin

Disfungsi Endothel
Aterosklerosis
(Bambang P; Prevent Vascular Damage 2013)

Result of All Risk Factors in Kidney Disease


Uremia-related

10 20 x Morbiditas / Mortalitas

Age
Family History
Gender Diabetes

Hypertensio
Dyslipidemia
Anemia
PTH
PO4
GFR
ADMA

LVH
CHF

Smoking
Inflamation

Non-modifiable

High oxidant stress


Modifiable

ET
CRP
ROS

Uremia-related

- AGEP
- AOPP
- Homosistein

PVD

CAD

MI
(Bambang P; Prevent Vascular Damage 2013)

NO Synthase

NO + Citrulline

L-Arginine

Oxidative
stress
ADMA
Asymetric Dimethyl
Arginine

Citrulline

DDAH
Dimethylamino
hydrolase

Renal excretion
JASN 15:S77, 2007

(Weiss et al., 2013; Obasi et al., 2012)

SKEMA PENGARUH STRES OKSIDATIF (ROS) PADA PGK


YANG BERAKIBAT PROGRESIFITAS ATEROSKLEROSIS

PGK
ROS
Agep
AOPP
Homosistein

Makrofag
Merusak
Gliko Protein & Nephrin

APOPTOSIS
ENDOTEL

Merusak IKB
NFKB

Albuminuri

Sitokin Pro Inflamasi


(TNF-, IL-1, IL-6)

ATEROSKLEROSIS
STROKE

KORONER

PGK

(Bambang P, 2012)

Angiotensin II
Endotelin
Vasokonstriksi
Iskemi
Defisiensi Aerob Metabolik
Gangguan pompa Na
Retensi Na
Retensi Air Intra Sel
Udem Intra Sel
Sel pecah / Onkosis
Robbin, 2007

The renin system plays a central role in


regulation of BP
Renin is released
into the vasculature
Juxtaglomerular cells

Glomerulus

Renin secretion is regulated by 4 mechanisms


Distal tubule

1
Pressure in the
afferent arteriole

Renin secretion is regulated by 4 mechanisms


3

Distal tubule
Na+ at the macula densa

Renin secretion is regulated by 4 mechanisms


Negative feedback by Ang II

Distal tubule

Renin Angiotensin
System (1)
Classical "circulating" system (RAS):

Angiotensin II

glomerular zone adrenal


glands

Aldosterone

ACE
Angiotensin I

Na+-retention
K+-loss
Renin

Angiotensinogen
Adapt. from Dominiak & Unger (eds.) in Ang IIAT1-Receptor Antagonists, Steinkopff (1997)

Renin
macula
densa

Blood
pressure

Na+

Sympathetic
system

Renin Angiotensin
System (2)
Local "tissue-bound" system (RAS):
Angiotensinogen
Renin

inactive fragments

Angiotensin I

ACE
Bradykinin

B1

B2

t-PA
Cathepsin G
Tonin
Chymases
Cathepsin G
CAGE

Angiotensin II

AT1

AT2

t-PA = tissue plasminogen activa


CAGE = chymostatin-sensitive
angiotensin generating enzyme

specific cellular response specific cellular response


Adapt. from Dominiak & Unger (eds.) in Ang II-AT1-Receptor Antagonists, Steinkopff (1997)

Renin Angiotensin
System (3)
Distribution of ACE:

10%

RAS

90%

Circulating (Plasma)

Local (Tissue)

Acute and short-term effects

PROTECTION
Long-term effects

cardiovascular/
renal homeostasis
Mod. from Dzau V, Arch Intern Med 153 (1993)

local "organ adaptation"

Pengelolaan Hipertensi
1.

Monitoring tekanan darah & faktor resiko

2.

Managemen pola hidup

3.

Farmakologi

Monitoring tekanan darah & faktor


Baseline tekanan darah diukur periodik pada semua
dewasa muda, lebih intensif pada pasien dengan :

1.Sudah/baru terdeteksi hipertensi


2.Punya kerusakan target kardiovaskular
3.Punya faktor resiko lainnya
4.Dalam terapi hipertensi

Managemen Pola Hidup


1. Tidak Merokok sama sekali, hindari secondhand
smoke

2. Aktivitas Fisik 4-7x/mg, 30-60mnt, skala sedang,


dinamik

3. Pengurangan Berat Badan BMI normal, LP <90cm


/ 80cm

4. Rekomendasi Diet tinggi serat/sayuran, rendah


lemak/kolest

Target Terapi
KONDISI

TEKANAN
DARAH

Hipertensi Sistolik/Diastolik

140/90

Diabetes

130/90

CKD

130/90

Proteinuria > 1gram/24jam

125/75

The Canadian Hypertension Education Program (CHEP) Guidelines, 2009

Diuretik
Short acting
Furosemid (lasix)2
chlorothiazide(Diuril)3

Intermediate
Hidroclrotiazide(Apo-Hydro, AquazideH,Dichlotride, Hydrodiuril, HydroSaluric, Hydrochlorot, Microzide,
Esidrex, and Oretic)4

Benzthiazide (Aquatag, Dihydrex, Diucen, Edemax, Exna, Foven ) 4

Long Acting
Chlorthalidone(Hygroton, Tenoretic)3
Hidroflumetazid (Saluron)4
Bendrofluazide(aprinox)4
Clopamide (aquex)4
Polythiazide(Renese)4
Spironolacton (Aldactone, Novo-Spiroton, Aldactazide, Spiractin, Spirotone, Verospiron or Berlactone) 5
Acetazolamide (Diamox)6

Obat-Obat Beta Blocker1


3. ISA(Intrinsic Sympatomimetic Activity) dan Non ISA

1. Selektif dan Non Selektif


a. Selektif:

b. Non Selektif

(Non Intrinsic Sympatomimetic Activity)

- Asebutolol

- Propanolol

- ISA:

- Metoprolol

- Timolol

- Pindolol

- Atenolol

- Nadolol

- Oksprenolol

- Bisoprolol

- Sotalol

- Alprenolol

- Pindolol
- Oksprenolol
- Alprenolol
- Labetalol*

c. Hidrofilik dan LIpofilik

- Sotalol

- Oksprenolol

- Nadolol

- Labetalol*

- Atenolol

- Metoprolol

b. Lipofilik

- Labetalol**
- Non ISA:
- Metoprolol

2. Hidrofilik dan Lipofilik


a. Hidrofilik

- Asebutolol

- Timolol

- Propanolol

- Bisoprolol

- Alprenolol

- Asebutolol
- Pindolol

- Atenolol
- Bisoprolol
- Propanolol
- Timolol
- Nadolol
- Sotalol

Caantagonis1
1. Long Acting:
Amlodipin(Norvasc)

Felodipin(Plendil)
Short Acting:
Dehidropiridin:

Nifedipin (Adalat)
Non Dehidroperidin

Diltiazem(Cardizem)
Verapamil(Calan, Isoptin)

KESIMPULAN
1. Pencegahan hipertensi harus sedini mungkin (pre-hipertensi)
2. Pengelolaan hipertensi harus diwaspadai faktor resiko yg lain
3.
4.
a.
b.
c.
5.
6.

(sindrom metabolik)
Program non-drug treatment wajib dijalankan penderita
Patogenesis hipertensi harus dipelajari dengan baik dalam rangka :
Memilih obat yang tepat
Memilih kombinasi obat
Meminimalkan efek samping
Target penurunan tensi sedapat mungkin mendekati ideal (harus
bertahap)
Pengelolaan krisis hipertensi harus memilih obat yg tepat, target
penurunan tensi sesuai protokol (supaya reversibel)

Terima kasih