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

Hipertensi

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

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

KLASIFIKASIJNC 7 Report 2003

WHO/ISH Statement on Management of Hypertension 2003

ESH/ESC Guidelines for the Management of Arterial Hypertension 2007

Primer: Belum diketahui (mis:genetik)

Sekunder :RenalAdrenalFaktor Biologi lainEksogen

ETIOLOGI

Hypertension and Chronic Renal Disease: Hemodynamic AbnormalitiesMean BPTotal SystemicVascular Resistance=XIncreased Cardiac Output Intravascular Volume Glomerular filtration Sodium excretion Extracellular Fluid Renal Nerve Activity Myocardial Performance Adrenergic ActivityIncreasedVasoconstriction Adrenergic Stimuli Angiotensin II Endothelin Endothelium-derived Contracting Factors ThromboxaneCardiacOutputDecreasedVasodilation Prostacyclin Nitric oxide EDHF*Textor SC. Atlas of Diseases of the Kidney, 2001.*Endothelium-derived Hyperpolarizing Factors

Hypertension ; basic mechanism..

Serangan StrokePenyakit ArteriGangguan pada Jantung

Gangguang Fungsi Ginjal

Hipertensi kronisMerusak autoregulasi ginjalPermeabilitas kapiler Proteinuri (mikroalbuminuri)Hukum HomeostasisReabsorbsi protein oleh sel tubulus berlebihan(stressor)Ekspresi sitokin :TNF Apoptosis, nekrosisIL1 Plag AterosklerorisTGF1FibrosisPatogenesis Komplikasi Hipertensi pada GinjalRobbin, 2005

Chronic hypertensionEndothelial StressorExpression TNFIL1TGF1ApoptosisPlaqueFibrosisNecrosisAtherosclerosisRenal FailureCoronary Heart DiseaseCerebralStrokeDementiaParkinson Hypertension Complication PathogenesisRobbin, 2008IL6HCRP

TNF

Hypotalamus

PG2+ ILIFEVER(Endogenic Pyrogen)Hepatosit SyntaseCoagulationStrong ActivationChachexiaSerum AmyloidFibrinogenCRP ContractionVascular smooth muscle cellsHeartVasodilatationShockFat CellsPermeabilityExudation Inflammation cellsCongestion Endhotel Tissue Factor Trombo ModulinShringkingProtealitic Membrane Receptor DisruptionEritropoietin Receptor DisruptionAnemiaVasopressor receptorsProteolitic(Brata Widjaya, 2009; Bambang P, 2010)ILIIL6KAKHEKTIN AppetiteCHACECTIC (THIN)

Disfungsi Endothel(Bambang P; Prevent Vascular Damage 2013)RESIKO KARDIOVASKULER DAN DISFUNGSI ENDOTHELNatriumENZIM NADPH OKSIDASETNF-AterosklerosisEndothelinPDGF

Result of All Risk Factors in Kidney DiseaseAge Family HistoryGender DiabetesUremia-related10 20 x Morbiditas / MortalitasHypertensioSmoking High oxidant stressDyslipidemiaInflamationNon-modifiableModifiableAnemia ETPTH CRP PO4 ROSGFR - AGEP ADMA - AOPP - Homosistein Uremia-relatedLVHCHFPVDCADMI(Bambang P; Prevent Vascular Damage 2013)

L-ArginineNO SynthaseNO + CitrullineADMAAsymetric DimethylArginineCitrullineRenal excretionDDAHDimethylaminohydrolaseOxidativestressJASN 15:S77, 2007

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

Merusak Gliko Protein & Nephrin APOPTOSISENDOTELMerusak IKBAlbuminuri Sitokin Pro Inflamasi (TNF-, IL-1, IL-6) NFKBATEROSKLEROSISSTROKEKORONERPGKPGK(Bambang P, 2012)MakrofagSKEMA PENGARUH STRES OKSIDATIF (ROS) PADA PGK YANG BERAKIBAT PROGRESIFITAS ATEROSKLEROSIS

The renin system plays a central role inregulation of BPJuxtaglomerular cellsGlomerulusRenin is released into the vasculature

Renin secretion is regulated by 4 mechanismsDistal tubulePressure in the afferent arteriole1

Renin secretion is regulated by 4 mechanismsNa+ at the macula densaDistal tubule3

Renin secretion is regulated by 4 mechanismsNegative feedback by Ang IIDistal tubule4

Renin Angiotensin System (1)

t-PA = tissue plasminogen activatorCAGE = chymostatin-sensitive angiotensin generating enzyme

Local "tissue-bound" system (RAS):AT1AT2Bradykinininactive fragmentsB2B1Angiotensin IIAngiotensin IAngiotensinogenACEReninspecific cellular responseChymasesCathepsin GCAGEt-PACathepsin GToninspecific cellular responseAdapt. from Dominiak & Unger (eds.) in Ang II-AT1-Receptor Antagonists, Steinkopff (1997)Renin Angiotensin System (2)

Mod. from Dzau V, Arch Intern Med 153 (1993)Renin Angiotensin System (3)PROTECTION

Monitoring tekanan darah & faktor resikoManagemen pola hidupFarmakologi

Pengelolaan Hipertensi

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

Sudah/baru terdeteksi hipertensiPunya kerusakan target kardiovaskular Punya faktor resiko lainnyaDalam terapi hipertensi

Monitoring tekanan darah & faktor resiko

Tidak Merokok sama sekali, hindari secondhand smokeAktivitas Fisik 4-7x/mg, 30-60mnt, skala sedang, dinamikPengurangan Berat Badan BMI normal, LP

Target TerapiThe Canadian Hypertension Education Program (CHEP) Guidelines, 2009

KONDISITEKANAN DARAHHipertensi Sistolik/Diastolik 140/90Diabetes 130/90CKD 130/90Proteinuria > 1gram/24jam 125/75

Diuretik

Short actingFurosemid (lasix)2chlorothiazide(Diuril)3

IntermediateHidroclrotiazide(Apo-Hydro, AquazideH,Dichlotride, Hydrodiuril, HydroSaluric, Hydrochlorot, Microzide, Esidrex, and Oretic)4Benzthiazide (Aquatag, Dihydrex, Diucen, Edemax, Exna, Foven )4

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

Obat-Obat Beta Blocker1

1. Selektif dan Non Selektif a. Selektif: b. Non Selektif- Asebutolol - Propanolol- Metoprolol - Timolol- Atenolol - Nadolol- Bisoprolol - Sotalol - Pindolol - Oksprenolol - Alprenolol - Labetalol*2. Hidrofilik dan Lipofilik a. Hidrofilik c. Hidrofilik dan LIpofilik- Sotalol - Oksprenolol- Nadolol - Labetalol*- Atenolol - Metoprolol b. Lipofilik - Timolol - Propanolol - Bisoprolol - Alprenolol - Asebutolol - Pindolol3. ISA(Intrinsic Sympatomimetic Activity) dan Non ISA (Non Intrinsic Sympatomimetic Activity) - ISA: - Pindolol - Oksprenolol - Alprenolol - Asebutolol - Labetalol** - Non ISA: - Metoprolol - Atenolol - Bisoprolol - Propanolol - Timolol - Nadolol - Sotalol

Caantagonis11. Long Acting: Amlodipin(Norvasc)Felodipin(Plendil) Short Acting: Dehidropiridin:Nifedipin (Adalat) Non DehidroperidinDiltiazem(Cardizem)Verapamil(Calan, Isoptin)

Pencegahan hipertensi harus sedini mungkin (pre-hipertensi)Pengelolaan hipertensi harus diwaspadai faktor resiko yg lain (sindrom metabolik)Program non-drug treatment wajib dijalankan penderitaPatogenesis hipertensi harus dipelajari dengan baik dalam rangka :Memilih obat yang tepatMemilih kombinasi obatMeminimalkan efek sampingTarget penurunan tensi sedapat mungkin mendekati ideal (harus bertahap)Pengelolaan krisis hipertensi harus memilih obat yg tepat, target penurunan tensi sesuai protokol (supaya reversibel)

KESIMPULAN

Terima kasih

*******Hypertension and Chronic Renal Disease: Hemodynamic Abnormalities In parenchymal renal disease, multiple factors can influence either cardiac output, systemic vascular resistance, or both. Blood pressure is the product of cardiac output multiplied by total peripheral vascular resistance. In most patients with chronic renal failure, studies suggest that cardiac output is normal or elevated, whereas overall extracellular fluid volume is expanded. Systemic vascular resistance is inappropriately elevated relative to cardiac output, reflecting a net shift in vascular control toward vasoconstriction. Several factors affecting vascular tone are disturbed in patients with chronic renal failure, including increased adrenergic tone and activation of the renin-angiotensin system, endothelin, and vasoactive prostaglandins. An additional feature in some disorders appears to depend on reduced vasodilation, such as in impaired production of nitric oxide.Reference: Textor SC. Renal Parenchymal Disease and Hypertension. Schrier RW (Editor). Atlas of Diseases of the Kidney, 2001;Vol3:Chapter2.4 (Figure 2.7). ISN Commission on Nephrology Informatics and NKF cyberNephrology. Internet Address - www.kidneyatlas.org/segments.htm

*Bila kita lihat di sini mekanisme dasar dari hipertensi ; ada beberapa faktor yang menyebabkan peningkatan tekanan darah, seperti peningkatan sistem simpatis,peningkatan angiotensin II, ekskresi natrium yang tidak adekuat..Dan seperti sejawat ketahui ; peningkatan tekanan darah ini menyebabkan kerusakan multi organ, seperti kerusakan ginjal maupun vaskular. Vaskular remodelling juga terjadi karena vasokonstriksi yg dihasilkan oleh angiotensin II, overactivity simpatis yang pada akhirnya menuju ke cardiac iskemia*Multi organ damage akibat hipertensi..****************************