Transcript Hypertensive Disorders in Pregnancy (I) Williams Obstetrics 22nd Edition Chapter 34 부산백병원 산부인과 조인호 Index        Diagnosis Etiology Pathogenesis Pathophysiology Prediction and Prevention Management Long-term consequences.

Hypertensive Disorders in
Pregnancy (I)
Williams Obstetrics 22nd Edition
Chapter 34
부산백병원 산부인과
조인호
1
Index







Diagnosis
Etiology
Pathogenesis
Pathophysiology
Prediction and Prevention
Management
Long-term consequences
2

Gestational Hypertension – 3.7% in 150,000
(National Center for Health Statics, 2001)

Pregnancy-related hypertension :

Pregnancy-related deaths(3201명 in US, 19911997)의 16% 차지

Black women are 3.1 times to die as white
women

Hypertensive disorders remain among the
most significant and intriguing unsolved
problems in obstetrics
3
Diagnosis

Gestational hypertension

Preeclamsia

Eclamsia

Superimposed preeclamsia (on chronic
hypertension)

Chronic hypertension
4
Gestational hypertension

BP≥ 140/90mmHg for first time during pregnancy

No proteinuria

BP returns to normal < 12 weeks’ postpartum

Final diagnosis made only postpartum

May have other signs or symptoms of
preeclampsia, for example, epigastric discomfort
or thrombocytopenia
5
Preeclampsia
￭ Minimum Criteria
- BP≥140/90mmHg after 20weeks' gestation
- Proteinuria ≥300mg/24hrs or ≥1+dipstick
￭ Increased certainty of preeclampsia
- BP≥160/110mmHg
- Proteinuria 2.0g/24hrs or ≥2+dipstick
- Serum creatinine >1.2mg/dl unless known to be previously
elevated
- Platelets <100000/mm3
- Microangiopathic hemolysis (Increased LDH)
- Elevated ALT or AST
- Persistent headache or other cerebral or visual disturbance
- Persistent epigastric pain
6
Preeclampsia

Diastolic hypertension ≥95mmHg


Worsening proteinuria



preterm labor 증가
Neonatal survival 변화없음
Epigastric or RUQ pain




Fetal death rate : 3배이상 증가
Hepatocellur necrosis, ischemia, edema that
stretches the Glisson capsure
AST/ALT상승 : 임신종결의 sign
Hepatic rupture : rare
Thrombocytopenia

severe vasospasm -> microangiopathic hemolysis ->
Platelet activation, aggregation
7
Severity of Preeclampsia
 Differentiation between mild & severe
preeclampsia can be misleading
-because apparently mild disease may
progress rapidly to severe disease

Rapid increase in BP followed by
convulsions is usually preceded by
unrelenting severe headache or visual
disturbances.
8
9
Eclampsia

preeclampsia+convulsion

Seizures that cannot be attributed to other
causes in woman with preeclampsia

Seizures are generalized and may appear
before, during, of after labor
10
Chronic hypertension


BP ≥140/90 mmHg before pregnancy or
diagnosed before 20weeks’ gestation (not
attributable to gestational trophoblastic
disease)
or
Hypertension first diagnosed after
20weeks’ gestation and persistent after
12weeks’ postpartum
11
Chronic Hypertension

Chronic hypertension은 임신후반기까지 진
단하기 어려움.


이유: BP decreases during the second and
early third trimesters in both normotensive and
chronically hypertensive women
Underlying hypertension의 원인

Essential familial hypertension (90%)
12

Underlying Causes of Chronic hypertensive
Disorder
Essential familial hypertension (hypertensive vascular disease)
Obesity
Atrterial abnormalities
Renovascular hypertension
Coarctation of the aorta
Endocrine diorders
Diabetes mellitus
Cushing syndrome
Primary aldosteronism
Pheochromocytoma
Thyrotoxicosis
Glomerulonephritis (acute and chronic)
Renoprival hypertension
Chronic glomerulonephritis
Chronic renal insufficiency
Diabetic nephropathy
Connetive tissue disease
Lupus erythematosus
Systemic sclorosis
Periarteritis nodosa
Polycystic kidney disease
Acute renal failure
13
Chronic Hypertension

Chronic HT

→ ventricular hypertrophy, cardiac
decompensation, cerebrovascular accidents,
renal damage

임신 때 superimposed preeclampsia가 생기
는 경우(최고 25%까지 보고됨, 1998, Sibai)
위의 합병증들이 더욱 호발함.
14
Preeclampsia superimposed on
Chronic Hypertension

New-onset proteinuria≥ 300mg/24hours in
hypertensive women but no proteinuria
before 20 weeks’ gestation

A sudden increase in proteinuria or blood
pressure or platelet count <100,000/mm3 in
women with hypertension and proteinuria
before 20weeks’ gestation
15
Superimposed preeclampsia

Placental abruption, growth restriction,
preterm delivery, death 의 위험성이 증가

일반적으로 “Pure” preeclampsia에 비해
증상이 훨씬 severe하고 종종 fetal growth
restriction이 동반된다.
16
Incidence and Risk Factor



Nulliparous women에게 흔함.
Incidence : 5% (wide variation)
Influence by


Nulliparous


Parity, race, ethnicity, genetic predisposition
Total :7.6% / severe : 3.3% (Hauth, 2000)
Risk factor

Chronic hypertension, multifetal gestation,
maternal old age(>35 yrs), obesity, AfricanAmerican ethnicity
17
Incidence and Risk Factor



Maternal weight and the risk of preeclampsia is
progressive.
BMI (Kg/m2)
<19.8
Morbidity (%)
4.3
>35
Gestation
twin
single
13.3
13
5
(Sibai, 2000)
Smoking during pregnancy reduced risk of hypertension
during pregnancy (Bainbridge,2005 ; Zhang, 1999)
Placenta previa also reduced the risk of hypertension
18
Incidence and Risk Factor
(Eclampsia)

Eclampsia

Somewhat preventable


1976 (williams Obstetrics 15th edition)


1/1750 deliveries
2000, National Vital Statistics Report, in US


1/1150 deliveries
1999


1/700 deliveries (Parkland Hospitial)
1983-1986


Receive adquate prenatal care
1/3250
1994, Douglas and Redman in UK

1/2000
19
Etiology

Basic concepts

Exposed to chorionic villi for the first time

Exposed to a superabundance of chorionic
villi, as with twins or hydatidiform mole

Have preexisting vascular disease

Genetically predisposed to hypertension
developing during pregnancy
20

Vascular endothelial damage with vasospasm,
transudation of plasma, and ischemic and
thrombotic sequelae.

Currently plausible potential cause (2003, Sibai)





Abnormal trophoblastic invasion of Uterine vessels
Immunological intolerance between maternal and
fetoplacental tissues
Maternal maladaptation to cardiovascular or
inflammatory changes of normal pregnancy
Diatary deficiencies
Genetic influences
21
Abnormal Trophoblastic
Invasion

In normal implantation, endovascular
trophoblasts invade the uterine spiral
arteries
22
23
Abnormal Trophoblastic
Invasion

In preeclampsia



Incomplete trophoblastic invasion
The magnitude of defective trophoblastic invasion of
the spiral arteries correlated with the severity of the
hypertensive disorder (2000, Madazli)
Using electron micorscopy





Endothelial damage
Insudation of plasma constituents into vessel walls
Proliferation of myointimal cells
Medial necrosis
Lipid and macrophage accumulates in myointimal
cells
24

Lipid-laden cells -> atherosis (Hertig, 1945)

Obstruction of the spiral arteriolar lumen by
atherosis may impair placental blood flow

Placental perfusion -> diminished
25
Immunological Factors

Theory




Formation of blocking antibodies of placental
antigenic sites might be impaired.
Number of antigenic sites provided by the placenta is
unusually great compared with the amount of
antibody, as with multiple fetuses. (Beer, 1978)
Effective immunization by a previous pregnancy is
lacking, as in first pregnancies.
The immunization concept was supported by

their observations that preeclampsia developed less
often in multiparas who had a prior term pregnancy
(Mostello, 2002; Trupin, 1996)
26
Immunological Factors

Early second timester - Develop
preeclampsia women



Lower proportion of helper T cells (Th1)
Th2 dominance, mediated by adenosine,
which is found in higher serum level in
preeclamptic compared with normotensive
women (Yoneyama, 2002)
These helper T lymphocytes secrete specific
cytokines that promote implantation, and
their dysfunction may favor preeclampsia
(Hayashi, 2004; Whitecar, 2001)
27
The Vasculopathy and the
Inflammatory Changes

The decidua contains an abundance of cells
that, when activated, can release noxious
agents. (Staff, 1999) -> mediators to provoke
endothelial cell injury

Preeclamsia due to an extreme state of
activated leukocytes in the maternal circulation
(Faas, 2000)


Cytokines : TNF-a, interleukin → oxidative stress
(highly toxic radicals)
Potential benefit of antioxidants to prevent
preeclampsia (Chappell, 1999; Zhang, 2002)
28
Nutritional Factors

Dietary deficiencies and Excesses over the
centuries have been blamed as the cause of
eclampsia.

Supplementation with various elements such as
zinc, calcium, and magnesium to prevent
preeclampsia (John, 2002)

Obesity, is a potent risk factor for preeclampsia

C-reactive protein, an inflammatory marker, was
shown to be increase in obesity, which in turn
was associated with preeclampsia (Wolf, 2001)
29
Genetic Factors

Hereditary hypertension is linked to
preeclampsia (Ness, 2003)

Preeclampsia- eclampsia is highly heritable in
sisters, daughters, granddaughters, and
daughters-in-law. (Chesley and Cooper, 1986)

60% concordance in monozygotic female twin
pairs (Nilsson, 2004)

HLA-DR4와 preeclampsia와의 연관성
(kilpatrick,1989)
30
Pathogenesis
Vasospasm

Vascular constriction →resistance and
subsequent hypertension

Maldistribution, ischemia of the
surrounding tissues → blood flow 의 감소
→ necrosis, hemorrhage, and other endorgan disturbances
31
Pathogenesis
Endothelial cell activation

Unknown factors (from placenta) are secreted
into the maternal circulation
→ activation and dysfunction of the vascular
endothelium.

Damaged or activated endothelial cells secrete
substances
→ promote coagulation and increase the sensitivity to
vasopressors
→changes in glomerular capillary endothelial
morphology
→increasd capillary permeability
→elevated blood concentrations
32
33
Increased Pressor Responses

Normally, pregnant women develop
refractoriness to infused vasopressors
(Abdul-Karim an Assali, 1961)

But, early preeclampsia women have
increased vascular reactivity to infused
norepinephrine and angiotensin II (Raab,
1956)
34
35
Increased Pressor Responses
Prostaglandins
Membrane phospholipid

In preeclampsia

Phospholipase
A2
Arachidonic acid

COX1,2
TXA2
Platelet
PGI2, PGE2
Endothelial
prostacyclin (PGI2)
production is
decreased
Thromboxane A2
(TXA2) secretion
by platelets is
increased
→ Increased
sensitivity to
infused
angiotensin II
→ vasoconstriction
36
Increased Pressor Responses
Nitric oxide

Synthesized from L-arginine by endothelial cells.
(potent vasodilator)

Nitric oxide maintains the normal low-pressure
vasodilated state characteristic of fetoplacental
perfusion (Myatt, 1992)

Preeclampsia is associated with decreased
endothelial nitric oxide synthase expression,
which increases cell permeability (Wang, 2004)
37
Increased Pressor Responses
Endothelins

Endothelin-1 (ET-1) :



potent vasoconstrictors
Produced by human endothelium
Plasma ET-1 is increased in normotensive
pregnant women, but women with
preeclampsia have even higher levels
(Ajne, 2003 ; Clark, 1992)
38
Increased Pressor Responses
Angiogenic factors

Vascular endothelial growth factor (VEGF),
Placental growth factor (PIGF),





which secretion increases in normal pregnancy
Promote angiogenesis
Induce nitric oxide
Vasodilatory prostaglandins
Paradoxically, VEGF is increased in serum from
women with preeclampsia, but its bioavailability
is decreased (Baker, 1995 ; Simmons, 2000)
39
Pathophysiology
Cardiovascular System

Increased cardiac afterload caused by
hypertension

Cardiac preload in preeclampsia



Pathologically diminished hypervolemia of
pregnancy
Iatrogenically increased by iv crystalloid or oncotic
solution
Extravasion into the extracellular space,
especially the lung
40
Cardiovascular System
Hemodynamic Changes

Preeclampsia


With clinical onset of preeclampsia



Cardiac output elevated before hypertension
developed than normal pregnancy.
Marked reduction in cardiac output.
Increased peripheral resistance.
By contrast, Gestational hypertension

Elevated cardiac outputs with development of
hypertension.
41
42
(Hankin, 1984)
43
Cardiovascular System
Blood volume

Blood volume in term




Normal pregnancy : 5000ml
Not pregnancy : 3500ml
Eclampsia : 3500ml
Hemoconcentration in preeclampsia



Vasoconstriction and Endothelial dysfunction with
vascular permeability.
Sevirity 와 연관되어 있지 않음.
Whereas, gestational hypertension have a normal
blood volume (Silver, 1998)
44
45
Cardiovascular System
Blood volume

With severe hemoconcentration, an acute fall in
hematocrit suggested resolution of preeclampsia

Intravascular compartment in eclamptic women is
usually not underfilled.
→ vasospasm and endothelial leakage of plasma has contracted
the space to be filled.
→ It persist some time after delivery when the vascular
endothelium repairs.

Sensitive to vigorous fluid therapy to expand the
contracted blood volume to normal pregnancy levels.

Sensitive to even normal blood loss at delivery.
46
Blood and Coagulation
Platelet



Thrombocytopenia → life threatening
Severe disease : < 100,000/uL
Platelet count 감소 -> indication of delivery -> 분만 후 35 days, 정상수준으로 회복

Platelet activation, aggregation, consumption ->
“exhausion” -> thrombocytopenia (Harlow, 2002)

HELLP syndrome : hemolysis (H) , elevated liver
enzymes (EL), and low platelets (LP) (Weinstein, 982)
Neonatal thrombocytopenia


Maternal thrombocytopenia와 연관이 없음. (Prichard, 1987)
47
Blood and Coagulation
Coagulation



PT, aPTT, fibrinogen level (routine lab
assessment of coagulation) -> preeclampsia 의
management에 필요하지 않음.
FDP의 증가 : unknown (but, hepatic
derangements 때문일 것으로 추정(Leduc, 1992) )
Thrombophilias :



clotting factor deficiencies -> early onset
preeclampsia
Antithrombin 을 투약하면 대조군에 비해
preeclampsia의 발생빈도를 낮출 수 있음(Chang, 1992)
Fibronectin


Glycoprotein-vascular endothelial cell basement
membrane
Preeclampsia의 예측인자로 활용
48
Blood and Coagulation
Fragmentation Hemolysis


Severe preeclampsia 때 LDH의 증가 –
hemolysis의 증거
Peripheral blood change :

Schizocytosis, spherocytosis, reticulocytosis
49
Volume Homeostasis
Endocrine changes

Renin, angiotensin, aldosterone


정상 임신에서는 증가
But, preeclampsia에서는 비임신의 정상 level
로 감소

기전 : Na + retension, hypertension 에 의해




Juxtaglomerular apparatus에서 renin분비가 감소
Angiotensinogen이 angiotensin I 으로 conversion (renin
의 작용) 이 감소
Angiotensin II의 감소 -> aldosterone의 감소
이런 상황에도 불구하고 preeclampsia 산모에서
Na retension이 계속 된다. (Brown, 1988)
50
Volume Homeostasis
Endocrine changes

Deoxycorticosterone (DOC)


Another potent mineralocorticoid
3rd trimester에 매우 증가



Maternal adrenal gland에서 분비가 증가된 것이
아니라 plasma progesterone의 전환임.
그러므로 Na retension이나 hypertension이 있어
도 감소하지 않음
-> preeclampsia의 발병과 지속에 중요한 역할을
담당할 것으로 기대.
51
Volume Homeostasis
Endocrine changes

Atrial Natriuretic peptide (ANP)



Blood vol. expansion에 의한 atrial wall
streching에 의해서 분비됨
Vasoactive한 물질, aldosterone, renin activity,
angiotension II, vasopressin의 action을 억제
하여 sodium과 water excretion을 조장함.
정상 임신에서도 증가하지만 preeclampsia때
는 더욱 증가
52
Volume Homeostasis
Fluid and Electrolyte Changes

Preclampsia산모

ECF vol. 이 정상산모보다 더욱 많이 증가.



Electrolyte concentration do not differ.
Electrolyte unbalance가 생기는 경우




Pathologic retension : endothelial injury
Vigorous diuretic therapy
Sodium restriction
Administration of water with sufficient oxytocin to
produce antidiuretisis.
Following eclamptic convertion -> lower HCO3
53
Kidney

Renal perfusion and glomerular filtration
감소 (in preeclampsia)



Due to vasospasm
But, Cr. Level의 감소는 일반적으로 심하지 않
음 -> severe한 경우는 2-3배 올라가기도 함.
(Pritchard, 1984)
Oligouria가 있는 preeclampsia산모에게서
intensive iv fluid therapy는 indication이 아님.
54
Kidney

Proteinuria




Preeclampsia-eclampsia 진단에 중요
Late하게 발생.
24hr UA가 중요
Anatomical changes


Glomeruli : 20%까지 증가
Glomerular capillary endotheliosis


Capillary endothelial swelling with subendothelial deposits
of protein materials
Acute renal failure


Tubular necrosis, cortical necrosis -> oligouria, anuria,
rapidly develped azotemia
원인 : HELLP synd. , placental abruption, postpartum
hemorrhage
55
Liver

Periportal hemorrhagic necrosis in the periphery
of the liver lobule


Serum liver enzyme 상승의 원인
Nonfatal case에서는 잘 보이지 않음



Hepatic rupture(more rare), subcapsular
hematoma(more common)을 일으킬 수 있음.
Treatment




Autopsy에서 주로 확인
Surgical intervention이 기본, life saving가능
Blood T/F이 도움.
Liver transplantation도 시행가능
Spontaneous hepatic rupture 의 mortality :30%
56
57
Liver

HELLP syndrome




Hemolysis, Elevated Liver enzyme and Low
Platelet
20% of severe preeclampsia and eclampsia
Adverse outcome : 40%
Other complication


Eclampsia (6%), Placental abruption (10%), ARF
(5%), pulmonary edema (10%), subcapsular liver
hematoma (1.6%)
Steroid Tx. - controversial
58
Brain

Common Sx.


Headache, visual disturbance – associated
convulsion (eclampsia)
Anatomical pathology

Gross hemorrhage – severe hypertension


Chronic hypertension이 있는 경우 더욱 흔함
Postmortem cerebral lesion

Edema, hyperemia, focal anemia, thrombosis,
hemorrhage
59
Brain

Neuroimaging study

CT



50%에서 abnormal finding
Hypodense cotical area – petechial hemorrhage
and infarction site에 해당 (at autopsy)
MRI



주로 post. Cerebral artery area에서 remarkable
change가 발견됨.
Convulsion과 직접적인 연관
Convulsion 의 25%는 cerebral infarction area가
있음.
60
61
Brain

Cerebral Blood Flow

Eclampsia : loss of autoregulation of cerebral
blood flow (Apollon, 2000)



Hyperperfusion – similar in hypertensive
encephalopathy.
Increased cerebral perfusion –> headache유
발
Cerebral vasospasm을 밝혀내지 못함.
62
Brain

Blindness



Rare
4hr to 8days 정도까지 지속되지만 결국 완전히 회복된다.
Visual disturbance


More common
Retinal detachement




Total loss를 초래 하지는 않음
주로 one side를 involve
수술적치료는 필요없음.
일반적으로 prognosis는 good, 1주일이내에 정상으로 돌아옴
63
Brain

Cerebral Edema

Sx



Mental change정도와 brain involvement정도는 어느정
도 비례한다. (CT, MRI상 변화)
Sudden severe blood pressure elevatoin



Letharge, confusion, blurred vision, coma
광범위한 vasogenic edema로 급격하게 악화
Blood pressure control이 중요함.
Electroencephalopgraphy


Eclampsia환자의 75%에서 abnormal finding이 나타남.
(48hr 이내)
50%이상은 1주일이상 지속하지만 , 3개월 이내에 대부
분 좋아진다.
64
Uteroplacental perfusion

Vasospasm ->


placental perfusion저하 -> perinatal mortality
and morbidity 증가의 중요한 요소
Measurement


Spiral a. : 500μm (정상), 200 μm (preeclampsia)
Placental blood flow


Inaccesibility, complexity, unsuitablity
DHAS sulfate-> estradiol-17B (in placenta)의
clearance rate로 간접측정 (Everett, 1980)
65
Uteroplacental perfusion

Doppler
Doppler measurement of blood velocity through
uterine artery.
-> estimate uteroplacental blood flow
 S/D ratio in preeclampsia : 증가
 Abnormal wave form -> fetal indication으로 c/sec필
요함.
 HELLP synd.의 18-36% : abnormal wave form을 보
임.
 Preeclampsia 산모는 정상산모에 비해 mean
resistance가 높음.

66
Prediction and Prevention

Prediction

Lots of attemption to predict preeclampsia in
early pregnancy -> poor sensitivity, poor
positive predictive value
67

Roll over test


28-32wks
Lt. lat. Recumbent position -> supine position



Hypertension유발되면 abnormal
이 경우, angiotension II infusion에도 abnormal반
응을 보임.
Positive predictive value (true positive) : 33%
(Dekker, 1990 ; Friedman and Lindhemier, 1999)
68

Uric acid


Decreased renal uric acid excretion -> elevated
serum uric acid level
Jacobson (1990)


Uric acid level > 5.9mg/dL at 24wks ; positive predictive
value : 33%
Weerasekera and Peiris (2003)

Serum uric acid levels did not vary significantly before
the detection of hypertension
69

Fibronectin


Endothelial cell activation -> elevated serum
cellular fibronectin level (Brubaker, 1992)
Clinical study, Paarlberg (1998)



Low sensitivity : 69%
Positive predictive value :12%
Clinical study, Chavarria (2003)



16wks-20wks, 378 low-risk nulliparas
Positive predictive value : 29%
Negative predictive value : 98%
70

Oxidative Stress


Lipid peroxides level증가 – antioxidants의 activity감
소 -> preeclampsia의 prediction가능 (Walsh, 1994)
Marker



Lipid peroxides: malondialdehyde
Pro-oxidants : iron, transferrin, ferritin, blood lipids, TG, free
fatty acid, lipoproteins, Vit C & E
Hyperhomocysteinemia


Atherosclerosis의 risk factor (non pregnant)
But, midpregnancy때 level이 높으면 preeclampsia의 risk가
정상보다 3-4배 증가함. (D’Anna, 2004; Hietala, 2001)
71

Cytokines


Released by vascular endothelium and
leukocytes
50개 이상의 cytokine이 preeclampsia때 증가



Interleukin, TNF – a
CRP증가
Not sufficiently predictive (Savvidou, 2002)
72

Placental peptides

Corticotropin releasing hormone, chorionic
gonadotropin, activin A, inhibin A


But, variation이 심해 investigator마다 결과가 다양
하게 나타남.
Angiogenic factor :VEGF, PlGF


First trimester때 PlGF, sFlt1 의 serum level증가
임상적으로 유용하나 의견이 분분.
73

Fetal DNA


Identification of Fetal DNA in marternal
serum -> prediction of preeclampsia (Zhong,
2001)
이유: endothelial activation and inflammation
이 발생하면 fetal cells and cellular material이
maternal circulation에 분비됨.
74

Uterine Artery Doppler Velocimetry


Second trimester – uteroplacental vacular
resistance측정 (by doppler of uterine artery)
Basic concepts


Impaired trophoblastic invasion of the spiral
arteries -> uteroplacental blood flow의 감소
Bower (1993)


Sensitivity : 78%
Positive predictive value :28%
75
Prevention

Dietary Manipulation



Salt restriction -> ineffective (Knuist, 1998)
Prenatal Ca supplementation -> significant
reduction in BP and incidence of preeclampsia
(Brucher, 1996)
But, Levin, (1997) 4600 nulliparas -> calcium
and placebo섭취 -> preeclampsia와
gestational hypertension의 incidence는 두 그
룹간의 차이가 없음.
76

Low dose aspirin


60mg aspirin -> reduce the incidence of
preeclampsia ; selective TXA2억제,
dominence of endothelial prostacyclin (Hauth,
1998, Wallenburg, 1986)
Caritis, 1998; CLASP Collaborative Group,
1994; Hauth, 1993, 1998; Rotchell, 1998;
Sibai, 1993a

Low-dose aspirin was ineffective in preventing
preeclampsia
77

Antioxidants

Davidge, 1992


Markedly reduced antioxidant activity in
preeclampsia women.
Chappel, 1999



283 high risk women
18-22wks , vit C & E versus placebo
Significant reduction in preeclampsia (11% / 17%)
78
진단 양성
질병
양성
음성
a
c
음성
b
d
Sensitivity : a/ a+c
Specificity : d/b+d
Positive predictive value : a/a+b
Negative predictive value : d/c+d
79