Pendahuluan

Hipertensi

Mata Kuliah Patofisiologi

Fakultas Farmasi
Universitas 17 Agustus 1945

HYPERTENSION SYNDROME IS MORE

THAN JUST BLOOD PRESSURE

Obesity

Decrease
Arterial
compliance

Endothelial
Dysfunction
Abnormal
Glucose
Metabolism

Abnormal lipid
Metabolism

Neurohormonal
Dysfunction

Accelerated
Atherogenesis

Renal-function
RenalChanges

LV Hypertrophy
And Dysfunction
Abnormal
Insulin
Metabolism

Blood-clotting
BloodMechanism
Change

Kannel WB. JAMA 1996, 275: 1571-1576; Weber MA et al. J Hum Hypertens 1991,
5: 417-423; Dzau VJ et al. J Cardiovasc Pharmacol 1993, 21 (Suppl 1): S1-S5

Kekerapannya bervariasi namun

diperkirakan sekitar 18%

Hipertensi tidak pernah berdiri
sendiri

Hypertension syndrome

Hipertensi adalah suatu masalah
kesehatan di masyarakat

B
L
O
O
D
P
R
E
S
S
U
R
E

Blood pressure is the force of blood

pushing from the heart against the
walls of the arteries throughout
your body.
Pressure is greatest when the heart
contracts and pumps the blood. This
is systolic pressure.
When the heart is at rest between
beats, blood pressure falls. This is
diastolic pressure.

Pengukuran Tekanan Darah

Posisi duduk > 5 minutes
Menggunakan ukuran
manset yang cukup
Manset setinggi jantung
Dengar suara korokof
untuk menentukan tekanan
darah dengan baik

TIPE TEKANAN DARAH

Short-term: HR and R
Daytime : degree of activity
Diurnal : BP fall during sleep
Seasonal : cold weather increases BP

Kenaikan TD yang palsu

Probandus : sakit, alkohol, minum kopi

Alat
: katup bocor, berisik
Pemeriksa : gangguan pendengaran
Cara pemeriksaan : manset tidak di tengah
manset terlalu pendek
dan rendah

Fisiologi
TD = cardiac output (co) x resistensi vascular (rv)

Patofisiologi hipertensi:
TD = cardiac output (co)

Regulation of BP:

x resistensi vascular (rv)

Take a look at the various factors that can

affect blood pressure.

BP = Cardiac Output x Peripheral Resistance

Endocrine Factors
Renin, Angiotensin, ADH, Aldosterone.
Neural Factors
Sympathetic & Parasympathetic
Blood Volume
Sodium, Mineralocorticoids,
Cardiac Factors
Heart rate & Contractility.

Patogenesis hipertensi
Cardiac
output
meningkat

Resistensi
perifer
meningkat

Preload meningkat
 Volume cairan meningkat krn asupan Na +++
atau retensi renal karena nefron atau GFR
Konstriksi Vena
 Stimulasi RAAS berlebihan
 Sistem saraf simpatis terlalu aktif
Konstriksi vaskular
 Stimulasi RAAS berlebihan
 Sistem saraf simpatis terlalu aktif
 Perubahan genetik membran sel
 Faktor karena endotel
Hipertropi vaskular
 Stimulasi RAAS berlebihan
 Sistem saraf simpatis terlalu aktif
 Perubahan genetik membran sel
 Faktor karena endotel
 Hiperinsulinemia karena obesitas atau metabolik sindrom.

Etiologic Classification:
Primary/Essential Hypertension (95%)
Increased peripheral resistance (sympathetic tone)
stress, hormonal, neural.
Genetic, familial, life style.
Secondary Hypertension (5-10%)
Renal : GN, RAS, Renin tumors
Endocrine : Cushing, OCP, Thyrotoxicosis Myxdema,
Pheochromocytoma, Acromegaly.
Vascular: Coarctation of Aorta, PAN, Aortic
insufficiency.
Neurogenic: Psychogenic, Intracranial pressure,
olyneuritis etc.

Patogenesis hipertensi
1.
2.
3.
4.
5.

Humoral system: malfungsi renin-angiotensinaldosteron-system (RAAS); natriuretic

hormon; insulin resisten dan hiperinsulinemia
Neuronal regulation: dan receptors
Peripheral autoregulatory
Vascular endothelial mechanism
Electrolytes and other chemicals

The renin-angiotensin-aldosterone system

Renin, a proteolytic enzyme formed in the granules of the
juxtaglomerular apparatus cells, catalyzes conversion of
the protein angiotensinogen to angiotensin I, a decapeptide.
This inactive product is cleaved by a converting enzyme,
mainly in the lung but also in the kidney and brain, to an
octapeptide, angiotensin II, which is a potent
vasoconstrictor that also stimulates release of aldosterone.
Also found in the circulation, the des-ASP heptapeptide
(angiotensin III) is as active as angiotensin II in
stimulating aldosterone release but has much less pressor
activity.

Renin-Angiotensin-Aldosterone
Plasma
volume
Detected by

&/Or

Kidney
(juxtaglomerular
apparatus)

Renin secretion is controlled by at least four mechanisms

that are not mutually exclusive:
A renal vascular receptor responds to changes in tension
in the afferent arteriolar wall;
A macula densa receptor detects changes in the delivery
rate or concentration of NaCl in the distal tubule;
Circulating angiotensin has a negative feedback effect
on renin secretion;
The sympathetic nervous system stimulates renin
secretion via the renal nerve mediated by receptors.

Renin-Angiotensin-Aldosterone
vasoconstriction

PVR

Angiotensin II
thirst

[Na+]
Via ACE
(Angiotensin
Converting
Enzyme)

Releases

Renin
Converts

ADH
(anti-diuretic
(antihormone)

Angiotensin II
Angiotensin I

Angiotensinogen

Adrenal
cortex

Fluid
volume

Releases

Aldosterone

BP!

Na+
reabsorption

Pathogenesis of Renovascular HTN:

GFR
Renin by JGA
Aldosterone

Angiotensin II

Sodium Retention
Blood Volume

Vasoconstriction
P. Resistance

Stimulasi simpatis
Stimulation of the sympathetic nervous system raises BP,
usually more in hypertensive or prehypertensive patients
than in normotensive patients.
Whether this hyperresponsiveness resides in the
sympathetic nervous system itself or in the myocardium
and vascular smooth muscle that it innervates is unknown,
but it can often be detected before sustained
hypertension develops.
A high resting pulse rate, which can be a manifestation of
increased sympathetic nervous activity

Hypertension

Defisiensi vasodilator
Deficiency of a vasodilator substance rather than excess of a
vasoconstrictor (eg, angiotensin, norepinephrine) may cause
hypertension.
The kallikrein system, which produces the potent vasodilator
bradykinin, is beginning to be studied.
Extracts of renal medulla contain vasodilators, including a neutral
lipid and a prostaglandin; absence of these
vasodilators
due to renal parenchymal disease or bilateral nephrectomy
would permit BP to rise.
Endothelial cells produce potent vasodilators (nitric oxide,
prostacyclin) and the most potent vasoconstrictor,
endothelin. Therefore, dysfunction of the endothelium could
have a profound effect on BP. The endothelium's role in
hypertension is being investigated.
Evidence that hypertensive persons have decreased activity of
nitric oxide is preliminary.

Electrolit (Na, Ca)

Abnormal Na transport across the cell wall due to a defect
in or inhibition of the Na-K pump (Na+,K+-ATPase) or due to
increased permeability to Na+.
The net result is increased intracellular Na, which makes
the cell more sensitive to sympathetic stimulation.
Because Ca follows Na, it is postulated that the
accumulation of intracellular Ca (and not Na per se) is
responsible for the increased sensitivity.
Na+,K+-ATPase may also be responsible for pumping
norepinephrine back into the sympathetic neurons to
inactivate this neurotransmitter. Thus, inhibition of this
mechanism could conceivably enhance the effect of
n o r e p i n e p h r i n e .

Changes in Preload

FAKTOR RISIKO UTAMA

- Hipertensi
- Merokok
- Obesitas (IMT 30 kg/m2)
- Kurangnya aktivitas fisik
- Dislipidemia
- Diabetes mellitus
- Mikroalbuminuria atau perkiraan LFG < 60 ml/men
- Umur > 55 tahun (laki-laki) atau > 65 tahun (wanita)
- Riwayat keluarga dengan PJK prematur (pria < 55 th, wanita <65 th)

fluid volume<
 preload<

( IMT: indeks massa tubuh, LFG: laju filtrasi glomerulus, PJK: penyakit jantung koroner)

 contractility
(Starlings Law)<

 blood pressure.

 cardiac output.

Hyperplastic Arteriolosclerosis:

KERUSAKAN ORGAN TARGET

Jantung
- hipertrofi ventrikel kiri
- angina atau pernah infark miokard
- pernah revaskularisasi koroner
- gagal jantung
Otak
- stroke atau Transient Ischemic Attack
Penyakit arteri perifer
Retinopati

Necrotizing arteriolitis:

Thrombosis
Narrow Lumen

Onion Skin Thickening

Of arterioles.

Fibrinoid Necrosis

Sistem kardiovaskular :
 Left ventricular hypertrophy,
 left atrial enlargement,
 aortic root dilatation,
 atrial and ventricular arrhythmias,
 systolic and diastolic heart failure,
 ischemic HD, dan
 congestive heart failure.

Different Cardiac
Morphologies in Heart
Failure
(a) Normal;
(b) dilated
cardiomyopathy;
(c) hypertrophic
cardiomyopathy;
(d) diastolic
dysfunction.

Left Ventricular Hypertrophy

The central nervous system

Subarachnoid Haemorrhage:

Hemorrhagic and atheroembolic stroke or encephalopathy.

BP>160/100mmHg risk of strokes & other cerebrovascular
diseases: hypertensive hemorrhage & encephalopathy,
lacunar-type infarctions, TIA, and dementia.

Cerebral Blood vessels

Special features:
Thin walled*
End arteries*
Cong. Aneurisms

Necrosis

Cerebral Infarction (Stroke)

Lacunar Infarct:

Retinopati hipertensi
Hemoraghi, eksudat, papil edem

Chronic hypertension
Arteriolosclerosis of deep
penetrating arterioles of
brain stem.
Single or multiple cavitary
infarcts lacunes.
Lenticular nucleus,
thalamus
Slit Haemorrhages.

Normal Retina - Fundoscopy

Retinopati hipertensi

Hypertensive Retinopathy:
Grade I: Thickening of
arterioles.
Grade II: Focal Arteriolar
spasms. Vein constriction.
Grade III: Hemorrhages
(Flame shape), dot-blot and
Cotton wool (ischemia) and
hard waxy exudates (lipid
deposition).
Grade IV: Papilloedema

Renal disease

Hypertensive Retinopathy:
Arteriosclerosis cause the arteriole light
reflex to become broad and dull silver wire
Generalized or focal retinal arteriolar
constriction pale.
Superficial flame-shaped hemorrhages.
Small white foci of retinal ischemia (cottonwool spots).
Yellow hard exudates, due to lipid deposition
deep in the retina.

Benign
Nephrosclerosis

Polycystic Kidney

Renal blood flow and elevated afferent glomerular arteriolar

resistance , glomerular hydrostatic pressure secondary to
efferent glomerular arteriolar constriction.
The result= glomerular hyperfiltration glomerulosclerosis
impairment of renal function.
Earlier detection hypertensive nephrosclerosis (test of
microalbuminuria)

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Renal Causes :

Renal Artery stenosis - Atrophy

Renal artery atherosclerosis

Polycystic Disease
Glomerulonephritis (A/C)
Renal artery stenosis
Renal vasculitis SLE
Renin producing tumors.

Leathery Granularity
Benign Nephrosclerosis

Polycystic Kidney ->

Kategori hipertensi
the Seventh Report of the Joint
National Committee of Prevention, Detection,
Evaluation, and Treatment of High Blood
Pressure (JNC VII), klasifikasi TD (mm Hg)

Classification of blood pressure for adults

(JNC VII)

1. Rekomendasi

untuk dewasa 18 tahun

BP
Classification
Normal

2. WHO/ ISH (International Society of

Hypertension)
Tidak seperti JNC 7, versi WHO/ISH tidak
ada klasifikasi "prehipertensi".

Pre-hypertension
Stage 1
Hypertension
Stage 2
Hypertension

SBP
mmHg

DBP
mmHg

<120

and <80

120-139
140-159

or 80-89
or 90-99

160

or 100

11

WHO Classification of Hypertension

Tekanan darah
SBP (mm Hg)

Grade 1

Grade 2

Grade 3

140-159

160-179

>/= 180

DBP (mm Hg)

90-99

100-109

>/= 110

MANIFESTASI
KLINIK
HIPERTENSI

HIPERTENSI

DIABETES

STROKE

Prognosis:
Sebagian besar individu yang terdiagnosis
hipertensi akan meningkat TDnya sebanding
dengan umur.
Hipertensi yang tidak diobati meningkatkan
risiko mortalitas sering disebut silent killer.
Hipertensi ringan sedang jika tidak diobati
dihubungkan dengan risiko atherosclerotic
disease pada 30% pasien dan organ damage
pada 50% pasien setelah hanya 8-10 tahun
onset.

Hipertensi krisis/ malignansi:

urgency dan emergency
Diastolik >120mmHg.
+ Target organ damage (kondisi emergency)
Cardiac decompensation: (C)HF, angina,
Encephalopathy: sakit kepala, kejang, gangguan
penglihatan atau gagal ginjal.
Turunkan TD dalam 1 jam/ secepat mungkin
(emergency )
vs
24 jam (urgency)

12

HEREDITER--LINGKUNGAN
HEREDITER
Umur

Normotensi

Pra--hipertensi
Pra

0 - 30 tahun

Hipertensi dini

20 - 40 tahun

Hipertensi (klinis)
Tanpa komplikasi

Hipertensi
maligna

30 - 50 tahun

Dengan komplikasi

Jantung P. Darah besar

Hipertrofi Aneurisma
Gagal
Diseksi
Infark

Otak
Ginjal
Iskemia
Sklerosis
Trombosis Gagal ginjal
Perdarahan

Faktor yang menentukan prognosis

terhadap risiko kardiovaskular
Hypertension

50% not diagnosed

50% diagnosed

50% not treated

50% treated

50% poorly controlled

50% well controlled

I. Menentukan stratifikasi

II. Faktor lain yang mempengaruhi

prognosis

Tinggi tekanan diastolik/sistolik

Laki >55 th, wanita >65 th
Kolesterol total >250 mg%
Diabetes melitus
Riwayat keluarga CVGD dini

HDL yang menurun

LDL meningkat
Mikroalbuminuria pada DM
IGT
Obesitas
Hidup malas
Fibrinogen meningkat

III. Kerusakan organ sasaran

IV. Kondisi klinik terkait

LVH (EKG, ekokardiografi, foto)

Proteinuria, kreatinin (1,2(1,2-2 mg%)
Plak aterosklerosis (foto/USG)
Penyempitan a.retina umum/lokal

CVD (strok, iskemia, perdarahan, TIA)

Penyakit jantung (IM, AP, GJK, revaskular)
Penyakit ginjal (ND, kreatinin >2 mg%)
Penyakit vaskular (diseksi, PPP)
Retinopati lanjut (perdarahan, papil edema)

13

Penurunan tekanan darah sistolik/diastolik

sebesar 10/5 mmHg menurunkan risiko
kejadian kardiovaskular

Perubahan Perilaku untuk HT

Pengobatan Hipertensi

Pengobatan untuk menurunkan tekanan
darah akan menurunkan insiden stroke
3535-40%, infark miokard 20
20--25%, gagal
jantung 50%

Penelitian epidemiologis UKPDS
melaporkan setiap penurunan 10 mmHg
rerata tekanan darah sistolik
berhubungan dengan penurunan risiko 12%
untuk segala komplikasi dengan DM, 15%
untuk kematian dengan DM, 11% untuk
infark miokard & 13% untuk komplikasi
mikrovaskular

Penurunan BB
Mengurangi garam < 2.4 gr/day
Diet kuat K, Ca and Mg
Stop alkohol
Olah Raga teratur
Mengurangi/stop merokok

Hipertensi Tanpa Terapi

Hipertensi bertambah
tinggi/berat, kematian umumnya
akibat komplikasi kardiovaskular

Secara umum yang berat serta
resisten bisa meninggal karena
stroke, yang retinopati lanjut
serta gangguan ginjal meninggal
karena GGT

Bagian terbanyak hipertensi
sedang meninggal karena PJK

Penyakit jantung masih
merupakan sebab utama kematian

14