HIPERTENSI = TEKANAN DARAH TINGGI

Dr.B Rudy Utantio, Sp.JP Konsultan Kardiologi

12/3/2013

Perjalanan penyakit kardiovaskuler

Sindrom Koroner Akut Trombosis koroner Aktivitas Iskemia miokard neurohor monal PJK Aterosklerosis

Aritmia & berkurangnya sel miokard

Remodeling

Mati menda dak

Pembesaran ventrikel

12/3/2013

GJ Faktor-2 risiko Dislipidemia HTN Kematian Diabetes Merokok, dll

Dzau V. Braunwald E. Am Heart J. 1991:121:1244-163

PENDAHULUAN

PERUBAHAN POLA MAKAN

Kadar lemak tinggi, protein tinggi, garam tinggi dan kandungan serat pangan (dietery fiber) yang rendah menyebabkan penyakit degeneratif yang meningkat : - penyakit jantung - diabetes mellitus - kanker - osteoporosis - hipertensi
12/3/2013 3

PREVALENSI HIPERTENSI

Di Dunia : 5-18% Di Indonesia : Hasil SKRT (1995) 83/1000 anggota RT: * Perempuan > pria * Di luar Jawa & Bali prevalensinya > Ungaran : 1.8% Silungkang : 19.4 % Lembah Balim : 0,6 %
12/3/2013 4

HIPERTENSI ~ TEKANAN DARAH TINGGI

Masih merupakan masalah kesehatan Silent Killer Pembunuh terselubung !!!! * Tidak ada keluhan * Tidak memberikan gejala - stroke - peny J Koroner - gagal ginjal, dll

12/3/2013

Fenomena gunung es

COMMUNITY STUDIES :
* POORLY CONTROLLED * THE RULE OF HALVES

Penderita Hipertensi Penderita HTN

Tidak terdignosa= 50% 50 % Tidak terdiagnosa

Terdiagnosa = 50 50 % % Terdiagnosa

Tidak berobat = 50 %50 % Tidak berobat

Berobat = 50 %% Berobat 50

Tidak teratur Tidak teratur = 5050 % %

Teratur 50 % % Teratur 50

12/3/2013

Hukum 50% kelompok penderita hipertensi

Tahu punya HTN Tidak minum obat Tidak kontrol Tahu punya HTN Sudah minum obat Tidak kontrol

25%

12.5%

12.5%
50%
Tidak tahu Tidak terdiagnosa

Tahu punya HTN Tetap minum obat Kontrol teratur

12/3/2013 Source

: Joffres et al. (1997) Am. J. Hypertension 10: 1097-1102

APAKAH TEKANAN DARAH ?

Tekanan dari jantung memompa darah mengalir ke seluruh pembuluh darah (+ oksigen ) mempertahankan kehidupan Jantung : Pompa bekerja non stop Pembuluh darah : Saluran untuk aliran darah Mengukur tekanan darah mengukur kekuatan darah pada saat menekan dinding pembuluh darah
8

12/3/2013

SPIGMOMANOMETER TENSI METER

Tekanan darah sistolik : * Nilai atas * Tekanan pada saat jantung memompa Tekanan darah diastolik : * Nilai bawah * Tekanan pada saat jantung istirahat

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TERMINOLOGI
1. Hipertensi Esensial = HT. Primer = HT. Idiopatik Kausa ? 95% 2. Hipertensi Sekunder Kausa (+) 5 % 3. Penyakit Jantung Hipertensi = Hypertensive Heart Disease ( HHD ) HT + Hipertrofi Ventrikel Kiri ( L.V.H )
12/3/2013 10

4. Hypertensive Heart Failure = H.H.F HT + Decompensatio cordis 5. Hipertensi Labil Tekanan darah kadang-kadang 6. Krisis Hipertensi : peningkatan TD mendadak (180/120) * HT. Gawat : kerusakan organ target yang progresif * HT Darurat : tidak disertai kerusakan organ target 7. White Coat Hypertension = Stress Hypertension = Office Hypertension = Responsive Hypertension 8. Hipertensi Sistolik TDS 140 mmHg 9. Hipertensi Diastolik TDD 90 mmHg 12/3/2013

11

WHITE COATHYPERTENSION
= Stress Hypertension = Office Hypertension = Responsive Hypertension 20 % - TD di Klinik - Perlu Pemeriksaan 24 jam - Pemeriksaan TD di rumah = ~ Pre Hipertensi !! ( T = 120/80 139/89)

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12

DEFINISI HIPERTENSI
T.D. Sistolik 140 mmHg dan atau T.D. Diastolik 90 mmHg

Perubahan tekanan darah : TDD : Selalu sama sepanjang waktu TDS : - Sering berubah-ubah

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13

Blood Pressure Classification ( JNC VII 2003)

BP Classification Normal Prehypertension Stage 1 Hypertension Stage 2 Hypertension SBP-mmHg < 120 120-139 140-159 160 and or or or DBP-mmHg < 80 80-90 90-99 100

Klasifikasi lain dari WHO-ISH 1999

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Classification of BP
JNC VI (1997)
Category Optimal Normal High-normal Hypertension Stage 1 140-159 90-99 SBP <120 <130 130-139 DBP <80 <85 85-89 Category Normal

JNC 7 (2003)
SBP <120 DBP <80 80-89

Prehypertension 120-139

Treat < 130/80 : DM, CKD Hypertension Stage 1 140-159 90-99

Stage 2
Stage 3

160-179
180

100-109
110

Stage 2

160

100

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15

MENGAPA T.D TINGGI ??

PATOFISIOLOGI HIPERTENSI
MEKANISME HIPERTENSI Tidak dapat dijelaskan dengan satu penyebab spesifik HT Essensial : Akibat Interaksi Dinamis : - faktor genetik - faktor lingkungan - faktor lain RUMUS TD = C.O X TAHANAN PERIFER
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CARDIAC OUTPUT = CO
= Curah Jantung = Darah yang dipompa oleh jantung = HR x SV

TD = HR x SV x Periferal resistance

TAHANAN PERIFER
* Ditentukan oleh diameter pembuluh darah arteri
12/3/2013 17

FAKTOR LAIN :

Retensi sodium Turunnya filtrasi ginjal Me saraf simpatis Me aktifitas RAA Perubahan membran sel Hiperinsulinemia Disfungsi endotel
18

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PATHOPHYSIOLOGY

(reduced nephron number)

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19

Peningkatan asupan sodium

Volume cairan meningkat (retensi cairan ) preload meningkat stroke volume meningkat cardiac output meningkat Hipertensi

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20

Penurunan filtrasi ginjal

Retensi sodium di ginjal Volume cairan meningkat Preload meningkat Stroke volume meningkat Cardiac output meningkat Hipertensi

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21

Regulasi Sistem Saraf Simpatik pada TD (Review)

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22

Disfungsi Endotel

Sintesis nitric oxide (NO) dari ginjal menurun (NO = primary endogen vasodilator) Hypertension

12/3/2013

23

Peningkatan Aktivitas Sistem Renin Angiotensin Aldosteron (RAA)

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24

RAAS

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25

The Renin-Angiotensin System

Circulating ( Liver ) Alternate Pathway Angiotensinogen Renin Inhibitors Renin Non Renin Pathway * t-PA * Cathepsin G * Tonin Local ( Tissue )

Angiotensin 1 Ace Inhibitors Converting enzyme Angiotensin 2 A-II12/3/2013 receptor blockers

Angiotensin Receptors

Non ACE Pathway * Chymase * CAGE * Cathepsin G

26

Renin mempunyai peran sentral pada regulasi tekanan darah Renin is released
into the vasculature Juxtaglomerular cells

Glomerulus
12/3/2013 27

Sekresi renin : 4 mekanisme

Distal tubule

1
Tekanan didalam Arteriol aferen

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28

Sekresi Renin : 4 mekanisme

2
Stimulasi saraf simpatik pada beta1 receptor didalam JGA Distal tubule

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29

Sekresi Renin : 4 mekanisme

3
Distal tubule Na+ didalam macula densa

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30

Sekresi Renin : 4 mekanisme

Negative feedback oleh Ang II
Distal tubule

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31

Renin-Angiotensin Cascade dan bradikinin

Angiotensinogen
Non-renin (e.g. tPA)

Renin Bradykinin

Angiotensin I
Non-ACE (e.g. chymase)

ACE
Inactive peptides
32

Angiotensin II
AT1
12/3/2013

AT2

ATn

Ang II & bradikinin Efek yang bertentangan : proatherogenic >< vasculoprotective Bradykinin
ACEI Ang I

ACE

+ Ang II AT1R Inactive peptides B2R ACEI

Vasoconstriction Aldosterone secretion Fibrosis Proliferation Oxidative stress Matrix formation Inflammation
12/3/2013

Vasodilation NO Prostaglandins EDHF tPA

Adapted from Ferrario CM, Strawn WB. Am J Cardiol. 2006;98:121-8. Adapted from Murphey L et al. Eur Heart J Suppl. 2003;5(A):A37-41. 33

PEMBAGIAN HIPERTENSI ( ETIOLOGI )

I.
II.

HT. Essensial / Primer ( 95 % ) HT. Sekunder ( 5 % )

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34

HIPERTENSI ESSENTIAL

Hipertensi Primer 95 % dari semua HT Etiologi tidak diketahui Merupakan : Complex Disease Multifaceted Disease Meliputi : - Disfungsi sistim saraf simpatis - Gangguan transport sodium - Hiperaktivitas sistim RAA - Defisiensi Renal Vasodilator Subtances - Kelebihan hormon Mineralokortikoid - Sodium Sensitivity - Obesitas
35

12/3/2013

KAUSA HT SEKUNDER
Renal * Polycystic Kidneys * Renovascular Disease B. Coarctatio Aortae C. Endrocrine : * Pheochromocytoma * Cushings Syndrome D. Pregnancy Induced HT (Pre/Eclampsia) E. Drugs / Substances
A.
12/3/2013 36

Hipertensi Renovaskuler

Stenosis arteri renalis menyebakan jaringan ginjal mengalami iskemia yang akan meningkatkan produksi renin. Akibatnya produksi angiotensin II bertambah (vasokonstriktor) dan meningkatkan produksi aldosteron

Penebalan fibromuskuler dinding arteri

Wanita muda < 40 th Faktor risiko ateroslerosis (+)

Atherosclerotic plaque

Abdominal bruit (+)

37

12/3/2013

PROSEDUR DIAGNOSIS HT
I. II.

III.
IV.

Anamnesis Pemeriksaan Fisik dan Evaluasi Klinik Pemeriksaan Laboraturium Pemeriksaan Lanjutan

12/3/2013

38

I. ANAMNESIS

12/3/2013

Tanpa keluhan Sakit kepala bagian belakang Berdebar, dada berat Sukar konsentrasi Sulit tidur Riwayat penyakit dahulu - HT + obat ? - Kehamilan ? DM ? - Penyakit ginjal Faktor resiko HT - Merokok - Makanan asin - Stress - Obat Kontrasepsi

39

II. Pemeriksaan Fisik dan Evaluasi Klinik

SPHYGMOMANOMETER

TIDAK

APAKAH TD 140/90

YA

HT
12/3/2013 40

III. PEMERIKSAAN LABORATURIUM

1. FOTO THORAX menilai bentuk dan ukuran jantung 2. Elektrokardiografi ( EKG ) menilai : * Hipertrofi V.ki ( LVH) * Abnormalitas Atrium ki * Iskemia / infark miokard 3. Laboratorium * Hemoglobin dan hematokrit (DL) * Urinalisis (dengan tes mikroalbuminuria dipstick dan pemeriksaan mikroskopik) * Kreatinin serum * Asam urat serum * Gula plasma puasa * Profil lipid 12/3/2013 * Elektrolit : NA, K, Cl

41

IV. PEMERIKSAAN LANJUTAN

OVERALL GUIDES FOR EVALUATION

DIAGNOSTIC PROCEDURE

Diagnosis
Chronic Kidney Disease (CKD) Renovascular Disease

Initial
Urinalysis, BUN or Creatinine, sonografy (USG) Bruit, PRA and renography before and one hour after 50 mg captopril Blood pressure in legs (ABI) Plasma Pottasium; plasma aldosterone; renin ratio AM plasma cortisol after 1 mg dexamethasone at bed time

Additional
Plasma Renin Assay ( PRA) , renal biopsy, IVP Arteriogram, renal vein resins

Coarctatio Primary Aldosteronism Cushings syndrome Pheochromocytoma

Aortogram, carotid USG Urinary pottasium, plasma aldosterone after saline infusion Urinary cortisol after variable doses of dexamethasone Urinary metanephirine and catechols; plasma catechols, basal and after 0,3 mg clonidine

Untuk Mencari penyebab hipertensi 12/3/2013 ( HT sekunder )

42

Renal Angiogram

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43

MANIFESTASI KERUSAKAN ORGAN SUBKLINIK

1. Cardiac * CAD ( Coronary Artery Dis ) * LVH ( Left Ventr. Hypertrophy ) * Left Ventr. Dysfunction * Cardiac Failure 2. Cerebrovascular * Transient Ischaemic Attack (TIA) * Stroke 3. Peripheral Vascular * Intermitten Claudication * Aneurysm * Epistaxis 4. Renal * S. Creatinin 1,5 mg/dl * Proteinuria : 1+ 5. Retinophaty 12/3/2013 * Papilledema / Exudates / Hemorhages

44

Otot jantung bilik kiri yang sangat tebal, tetapi bagian lain dari jantung tidak membesar.Keadaan ini khas pada Penyakit Jantung Hipertensi (HHD).

12/3/2013

45

Otot jantung bilik kiri yang sangat tebal Pada penderita HTN yang tidak berobat selama bertahun-tahun.
12/3/2013 46

Funduskopi
Untuk mencari adanya Retinopati HT. ( Keith Wagner I-IV )

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47

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48

12/3/2013

49

TUJUAN PENGOBATAN HTN

1.
2.

3.

Menurunkan TD Mencegah / mengurangi kerusakan organ target Mengurangi morbiditas dan mortalitas penyakit kardiovaskuler

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50

PENATALAKSANAAN
INDIVIDUALIZED TREATMENT Jika modifikasi gaya hidup tidak menurunkan tekanan darah yang diinginkan, terapi farmakologis harus diberikan !

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51

PENGELOLAAN HIPERTENSI
I. II.

Non Farmakologik Farmakologik = Obat

Terapi Non Farmakologik = Lifestyle Modifications S Stop Merokok E Exercise Teratur H Hindari stress ---- Kelola stress A Awasi minum alkohol / konsumsi sodium T Turunkan berat badan O.A. H : - Efek samping obat - Kwalitas hidup - Biaya 12/3/2013

52

Algorithm for Treatment of Hypertension

Lifestyle Changes

LIFESTYLE CHANGES !!!

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Weight reduction
Without Compelling Indications

Dietary sodium reduction Stage 2 Hypertension DASH eating plan

ACEI, or ARB, or BB, or CCB)

With Compelling Indications

Stage 1 Hypertension
(SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.

(SBP >160 or DBP >100 mmHg) Stage 2 Hypertension 2-drug combination for most (SBP >160 or DBP >100 mmHg) (usually thiazide-type diuretic and 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Physical activity
Not at Goal Blood Pressure
12/3/2013

Moderation of alcohol consumption

Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.
53

12/3/2013

54

Tatalaksana Hipertensi
Merubah gaya hidup merupakan tatalaksana yang paling penting !!! Olah raga yang teratur secara langsung dapat menurunkan TD dan BB Setiap penurunan BB 1,8 kg dapat menurunkan TD sebesar 1 mmHg (Groer, 2001)
12/3/2013 55

12/3/2013

56

Algorithm for Treatment of Hypertension

Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

(SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.

(SBP >160Stage or 2DBP >100 mmHg) Hypertension (SBP >160 or DBP >100 mmHg) Drug(s) for the compelling Stage 2 Hypertension Stage 1 Hypertension 2-drug combination for most 2-drug combination for most (usually indications (usually thiazide-type diuretic and ACEI, or ARB, ordiuretic BB, or CCB) thiazide-type and ACEI, or ARB, or BB, or CCB)
(SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Without Compelling Indications

Stage 2 Hypertension

With Compelling Indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.

Not at Goal Blood Pressure

12/3/2013

Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist.

57

1999 WHO-ISH Guidelines Obat Anti Hipertensi Lini Pertama

Diuretics Beta-Blockers ( BB ) ACE inhibitor ( ACEI ) Calcium antagonists ( CCB ) Alpha-Blockers Angiotensin II Receptor Blockers ( ARB )

Guidelines Subcommitee.1999.WHO-Intl Society of Hypertension. 12/3/2013 Guidelines for Management of Hypertension. J Hypertens 1999;17:151-83.

58

Guidelines for Initiation of AntiHypertensive Treatment (Compendium of ESC Guidelines 07)

Thiazide diuretics Beta-Blockers ( BB ) ACE inhibitor ( ACEI ) Calcium antagonists ( CCB ) Angiotensin II Receptor Blockers ( ARB )

Choice of antihypertensive drugs ESC12/3/2013 Guidelines Desk Reference 2007

59

JNC VI NEW BP GOALS <140/<90 and lower if tolerated <130/<85 in diabetics (types 1 & 2 ) <130/<85 in cardiac failure <130/<85 in renal failure <125/<75 in renal failure with proteinuria > 1.0 gm/24 hr
12/3/2013

WHO ISH NEW BP GOALS <140/90 In Elderly < 130/85 in young, middle-aged <130/85 in diabetic

60

ESHESC Recommendations for Combining BP-lowering Drugs Diuretics

b-blockers Angiotensin receptor blockers (ARBs)

a-blockers

Calcium channel blockers (CCBs)

Angiotensin-converting enzyme (ACE) inhibitors

Preferred combination 12/3/2013 Less frequently used/ combination used as necessary
Task Force of ESHESC. J Hypertens 2007;25:110587 Copyright 2007, with permission from Lippincott Williams and Wilkins
61

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Adverse Effects of Commonly Used Antihypertensive Agents

Diuretics
Muscle cramps Impotence Gout Glucose Intolerance Hypokalemia Hyperuricemia Hypomagnesemia Hypercalcemia

BBs
Depression Sleep disorders Exercise Intolerance Dysiplidemia Glucose Intolerance Impotence

CCBs
Edema Flushing Headache Dizziness GI disorders Changes in heart rate

ACEIs
Cough Rash Hyperkalemia Angioedema

ARBs
Hyperkalemia Angioedema ( rare )

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65

PROGNOSIS
Tergantung : 1. Stratifikasi Risiko Kardiovaskuler : * Rendah * Sedang * Tinggi * Sangat tinggi 2. Kerusakan organ target 3. Kondisi Klinik yang berhubungan 4. Respon ke pengobatan 5. Kepatuhan penderita
12/3/2013 66

TIGA PEDOMAN UNTUK PENDERITA TEKANAN DARAH TINGGI

1.

2.

3.

Periksakan tekanan darah secara teratur Minum obat seperti yang dianjurkan dokter Patuhi dengan baik segala nasehat dokter
67

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Aetiology of Hypertension

Primary 90-95% of cases also termed essential of idiopathic Secondary about 5% of cases Renal or renovascular disease Endocrine disease

Phaeochomocytoma Cusings syndrome Conns syndrome Acromegaly and hypothyroidism

Coarctation of the aorta Iatrogenic

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Hormonal / oral contraceptive NSAIDs

71

This left ventricle is very thickened (slightly over 2 cm in thickness), but the rest of the heart is not greatly enlarged. This is typical for hypertensive heart disease. The hypertension creates a greater pressure load on the heart to induce the hypertrophy.
12/3/2013 72

The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many years. The myocardial fibers have undergone hypertrophy.
12/3/2013 73

Logical Combinations

Diuretic

Diuretic
b-blocker CCB ACE inhibitor

bblocker * -

CCB

ACE inhibitor -

ablocker -

a-blocker * Verapamil + beta-blocker = absolute contra-indication

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74

ACE Inhibitor Side Effects

Cough (15% of patients. Is reversible) Taste disturbance (reversible) Angiodema First-dose hypotension Hyperkalaemia ( esp. in patients with type II diabetes and renal dysfunction)

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75

Follow-up

For patients with BP stabilised by management, follow up should normally be three monthly (interval should not exceed 6 months), at which the following should be assessed by a trained nurse:

* * * *

Measurement of BP and weight Reinforcement of non-pharmacological advice General health and drug side-effects Test urine for proteinuria (annually)

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76

ECG

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77

A Muscular Pump

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78

Left Coronary System

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79

Diuretics

Thiazides
Work by sodium and water excretion Side effects include hypokalemia, hyperuricemia and glucose intolerance Less effective in severe renal dysfunction

Potassium sparing diuretics

Aldosterone antagonists

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80

ACE (angiotensin converting enzyme) Inhibitors Method of action

Block the enzyme that converts angiotensin I to angiotensin II ( a vasoconstrictor) Promote vasodilatation Lowers aldosterone secretion Cough Rash Angioneurotic edema Taste disturbance Hyperkalemia especially with renal impairment

Side effects

Especially useful

HTN with CHF or DM

Pregnancy Bilateral renal artery stenosis
81

Contraindications

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FDA-Approved Indications for ACE Inhibitors

Left Prevention of Myocardial Congestive Ventricular Infarction, Stroke, and Hypertension Heart Failure Dysfunction Cardiovascular Death

All ACE Inhibitors

Captopril Captopril Enalapril Enalapril

Fosinopril Lisinopril

Ramipril

Lisinopril
Quinapril
12/3/2013

Ramipril

Ramipril

82

Angiotensin II receptor blockers

Method of action

Block the AT1 receptor causing a fall in peripheral resistance

Very similar to ACE inhibitors but does not cause a cough

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83

Beta Blockers

Decrease BP by reducing cardiac output and inhibiting sympathetically mediated renin release from the kidney Relative contraindications

Asthma/COPD Decompensated CHF Raynauds phenomenon Peripheral vascular disease Depression Tiredness Cold hands and feet Impotence and sexual dysfunction May mask the effect of hypoglycemia in DM
84

Side effects

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Beta Blockers

Decrease BP by reducing cardiac output and inhibiting sympathetically mediated renin release from the kidney Relative contraindications

Asthma/COPD Decompensated CHF Raynauds phenomenon Peripheral vascular disease Depression Tiredness Cold hands and feet Impotence and sexual dysfunction May mask the effect of hypoglycemia in DM
85

Side effects

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Secondary HTN who to evaluate?

Accounts for <5% of all cases of elevated BP Recent or sudden onset Young people with no family history Patients resistant to treatment

Uncontrolled

HTN on adequate doses of three medicines one of which is a diuretic

Patients who have

Physical

12/3/2013

findings (abdominal bruits) Biochemical abnormalities (unprovoked hypokalemia)

86

Most common causes of secondary HTN

Renovascular HTN Catecholamine excess states Mineralocorticoid excess states

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87

Renovascular HTN

Stenosis of a renal artery increases renin production from the ischemic kidney which causes increased production of angiotensin II (vasoconstrictor) and increased production of aldosterone

Fibromuscular thickening of the arterial wall

Women younger than 40

Atherosclerotic plaque

Older people with risk factors for atherosclerosis

Listen for an abdominal bruit

88

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Renal Angiogram

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89

Angioplasty

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90

Right Stent in-situ

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91

Coronary Stents

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92

Endocrine Abnormalities
Hypokalemia (low potassium) in the absence of diuretic therapy may indicate a state of mineralocorticoid excess Excess aldosterone production (Conns) Excess glucocorticoid production (Cushings) Hyperthyroidism

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Cushings Syndrome Hypercortisolism

Aetiologies

Iatrogenic excess corticosteroid administration ACTH hypersecretion by the pituitary Bilateral adrenal hyperplasia

Signs/symptoms hypertension, central obesity, abdominal striae, buffalo hump, moon facies, hirsuitism, easy bruising, hyperglycemia, hypokalemia Evaluation elevated free urinary cortisol, lowdose dexamethasone suppression test Treatment resection +/- irradiation
94

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Primary Hyperaldosteronism
Due to excess aldosterone production (Conns) Usually due to an adrenal adenoma Features include hypertension, hypokalemia (tetany), polyuria, elevated urinary potassium, elevated plasma/urine aldosterone, low plasma renin Treatment

12/3/2013

Adrenalectomy for Conns Spironolactone for bilateral hyperplasia

95

Pheochromocytoma
Catecholamine secreting neoplasms of the adrenal glands (medulla) or extra-adrenal chromaffin tissue Headache, diaphoresis and tachycardia Severe HTN with the induction of anesthesia The diagnosis depends on the demonstration of increased excretion of catecholamines or their major metabolites in the urine

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96

Hypertension Defined
Hypertension (HTN) is defined as sustained abnormal elevation of the arterial blood pressure (Brashers, 2006, p.1).

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Physiology of Blood Pressure I Blood Pressure =

Cardiac Output (CO) X Peripheral Vascular Resistance
Components of Blood Pressure Systolic Pressure Diastolic Pressure Pulse Pressure Mean Arterial Pressure

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98

Physiology of Blood Pressure II Mechanisms of Blood Pressure

Short-term regulation

Neural Mechanisms
Humoral Mechanisms

Long-term regulation
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Guidelines
The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) uses the following guidelines to define HTN in adults: (Brashers, 2006, p.1) Category
Normal Pre-hypertension Stage 1 hypertension Stage 2 hypertension
12/3/2013

Systolic

Diastolic

<120 120-139

and or

<80 85-89

140-159
>160

or
or

90-99
>100
100

Epidemiology I

Epidemiology
The most common primary diagnosis in the United States, 50 million American affected. Only 70% are aware they have HTN Of those aware of their HTN, only 50% are being treated. Only 25% of all hypertensive patients have their BP under control HTN is a risk factor for coronary artery disease (CAD), congestive heart failure (CHF), stroke, and renal failure 12/3/2013 101

Epidemiology II
Epidemiology (cont) Cardiovascular risk increases two-fold for each 20mm/Hg rise in systolic pressure or each 10mm/Hg rise in diastolic pressure

Risk factors in all populations include age, obesity, sedentary life-style, family history, smoking, alcohol, high sodium intake, low potassium or magnesium intake, and the use of NSAIDS

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102

Pathophysiology I

Primary Hypertension
Genetics

Environment

Neurohormonal

mediators
12/3/2013 103

Pathophysiology II
Contributing factors for Primary HTN:

Increased activity of:

sympathetic nervous system (SNS) Renin-angiotensin-aldosterone system (RAA)

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Defects in natriuretic hormone function Inflammation Obesity Endothelial dysfunction Insulin resistance
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Pathophysiology III
Secondary Hypertension Causes Complications Treatment

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Pathophysiology IV
Other forms of HTN Complicated HTN Malignant HTN Hypertensive Crisis

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Differential Diagnosis
1.

2.

Rule out isolated incident of increased blood pressure. Rule out secondary hypertension related to: Renal disease Cushing's disease Pheochromocytoma Hyperthyroidism Hyperparathyroidism
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Clinical Manifestations I
Physical exam: Abdomen Funduscopic Vascular Cardiac Pulmonary Neurological Lab tests: Urinalysis Blood Chemistry ECG Renal ultrasound Echocardiogram Vascular studies

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Management
Primary goal is to reduce cardiovascular and renal morbidity and mortality. Other keys to management are: Prevention Patient education Life-style modification Medication
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Management
Medications Diuretics- Thiazides (HCTZ), Loop (Furosemide), Potassium-sparing (Spironolactone) Beta-Blockers- Atenolol, Nadolol, Propranolol

ACE Inhibitors- Benezapril, Captopril, Cilizapril

Ca+ Channel Blockers- Nifedipine, Verapamil Alpha blockers- Prazosin, Terazosin ARBs- Losartan, Valsartan Vasodilators- Apresoline
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Outcome
Follow up Frequent monitoring is necessary until BP is under control. Once under control office visits can be decreases, with limited laboratory tests. Lipids should be checked yearly. ECG every 2-4 years, as indicated by initial ECG
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Complications
Complications as a result of HTN include:
Stroke Dementia Myocardial Infarction Congestive Heart Failure Retinal Vasculopathy Aortic Dissection
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Renal Disease or Failure

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Referral
A patient should be referred when: BP remains uncontrolled after three concurrent medications

Uncontrolled BP and signs and symptoms of endorgan damage

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Hospitalization
Hospitalization should be considered if:
Very high BP
Severe headache Chest pain Neurologic symptoms Altered mental status Acutely worsening renal failure S & S of hypertensive emergency
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Conclusion
Use 24 hour ambulatory BP monitors to properly evaluate HTN Treat very aggressively Treat other cardiovascular risk factors Watch for secondary causes of HTN

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Essential hypertension
Sites of regulation of blood pressure
BP
Cardiac output

Peripheral resistance

Blood volume

Renal perfusion

Baroreceptors

Vasoconstriction Na and H2O excretion Aldosterone Angiotensin II Renin Urinary output

+

Urinary output

Renin Angiotensin II Aldosterone Na+ and H 2O excretion

Parasympathetic Sympathetic

Heart rate contractility

Heart rate contractility

Sympathetic Parasympathetic

Vasoconstriction

Baroreceptors

Renal perfusion

Blood volume

Peripheral resistance

Cardiac output

BP
Site of action of anti-hypertensive drugs Angiotensin II Antagonists 12/3/2013 Methyldopa Beta-blockers Vasodilators Ca Channel Blockers a-blockers Ace inhibitors Diurectics 117

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RATIONALE OF DUAL RAS BLOCKADE WITH ACE-l & AT1 RECEPTOR BLOCKADE (INHIBITION OF CONSECUTIVE RAS STEPS)

1. Minimizing ESCAPE (Incomplete blockade) occurring with single site RAS blockers
Suggested mechanisms for ESCAPE:
a. Progressive clearance from the body of the drug at the end of dosing interval

b. Counter-regulatory reactive rise in plasma active renin that increases ATl & ATll proportionally to the suppression of the ATII negative feedback on renin release (this mechanism contributes to the flat dose response curve of BP measured at trough reported for RAS blockers) c. ATll generation by pathways other than Renin & ACE (CAGE-Chymotrypsin-like Angiotensin Generating Enzyme and Chymase)

2. Additional BP lowering
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Modified from AZIZI M. and MENARD J; Circulation 1/6/2004 109; 2492-2499

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Figure 14-1

BION 3202
Lecture 2. Contraction of Heart Tissue

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Sodium Channel Gating

Na+ Na+

Na+

Extracellular

+++

Intracellular

Activation gate Inactivation gate

Closed

Open

Inactive

Holding potential (-80mV)

0mV

INa+
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Activation phase

Inactivation phase

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Na

Na Na Na

Na Na

Na

Ionic Current
Na Na Na Na Na Ca Ca Ca Ca

Ca Ca Ca Ca Ca

IK1

Cell membrane

NCX

NKP

INa

IL,Ca
K K K K K K

IKr
K K K K K K

IKS
K

SR ATPase
Ca Ca Ca Ca

RyR Sarcoplasmic Reticulum

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Ca

Ca Ca Ca Ca

Ca

Ca

Ionic Currents: A few more

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Figure 14-10b

Early Morning Surge Can Trigger Events

Early morning BP surge
BP rise Plaque fissure Catecholamine surge Increased heart rate Arterial thrombosis Shear stress

Early morning hypercoagulable state

CV EVENTS
Weber MA. Am J Cardiol. 2002;89(suppl)27A33A.
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Aliskiren : Hits the Target

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Endocrine Abnormalities
Hypokalemia (low potassium) in the absence of diuretic therapy may indicate a state of mineralocorticoid excess Excess aldosterone production (Conns) Excess glucocorticoid production (Cushings) Hyperthyroidism

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Cushings Syndrome Hypercortisolism

Aetiologies

Iatrogenic excess corticosteroid administration ACTH hypersecretion by the pituitary Bilateral adrenal hyperplasia

Signs/symptoms hypertension, central obesity, abdominal striae, buffalo hump, moon facies, hirsuitism, easy bruising, hyperglycemia, hypokalemia Evaluation elevated free urinary cortisol, lowdose dexamethasone suppression test Treatment resection +/- irradiation
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Primary Hyperaldosteronism
Due to excess aldosterone production (Conns) Usually due to an adrenal adenoma Features include hypertension, hypokalemia (tetany), polyuria, elevated urinary potassium, elevated plasma/urine aldosterone, low plasma renin Treatment

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Adrenalectomy for Conns Spironolactone for bilateral hyperplasia

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Pheochromocytoma
Catecholamine secreting neoplasms of the adrenal glands (medulla) or extra-adrenal chromaffin tissue Headache, diaphoresis and tachycardia Severe HTN with the induction of anesthesia The diagnosis depends on the demonstration of increased excretion of catecholamines or their major metabolites in the urine

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Hypertensive Crises

HTN with clinical features of

Hypertensive encephalopathy Intracranial hemorrhage Unstable angina and acute myocardial infarction Aortic dissection Papilledema

Use IV agents to reduce the BP by no more than 25% in the 2 hours and to no less than 160/100mmHg during the next 6 hours Extreme care must be taken not to cause renal, coronary or cerebral ischemia by dropping the BP too quickly
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