Faculty of Medicine
Postgraduate Medical & Health Studies Board
Department of Obstetrics & Gynecology
By
Dr. Khalid Hussein Bakheit
M.B.B.S (University of Khartoum)
Supervisor
Prof. A.S.M.A Gerais
M.D., FRCOG,
Department of Obstetrics and Gynaecology,
Faculty of Medicine, University of Khartoum
October 2002
Contents
page
Dedication
Acknowledgement i
Abstract (English).. ii
Abstract (Arabic) iii
Abbreviations . iv
List of Tables.... v
List of Figures . vi
Chapter One
Introduction1
Literature review .2
1-1 Indroduction......2
1-2 Definition ...2
1-3 Features of PE .3
1-4 Classification of HELLP syndrome6
1-5 Risk factors of abruptio placentae and eclampsia..7
1-6 Hyperuricaemia and cardiovascular disease...8
1-7 Chronic hyperuricaemia and renal disease..8
1-8 Relevance of plasma uric acid to pregnancy
induced hypertension.9
1-9 Plasma purine turn over in normal
pregnancy
Acknowledgement
I would like to thank with great pleasure my honorable supervisor; Prof. A.S.M.A
Gerais, Department of Obstetrics and Gynaecology, University of Khartoum, for
his kind guidance, meticulous supervision with his kind smile all the time during
the hot afternoons, and discussion of all aspects of the thesis. His valuable advice,
comments and criticism are highly appreciated.
Great thanks to pregnant ladies, inpatients and in the antenatal clinic who were
never reluctant to give any information and kindly donated their samples to the
purpose of this study.
Abstract
The value of serum uric acid as indicator of severity of preeclampsia among Sudanese patients was studied in the period
1st-May- to end of September 2002.
The study was carried out as a multicentre study in the Khartoum
state in different maternity units, including, Khartoum teaching
Hospital, Omdurman maternity hospital, Khartoum North teaching
hospital, and Omdurman Military hospital.
Informations were collected from the patients by taking history
through a questionnaire, examination and analysis of serum uric
acid and urine for protein. Number of patients admitted with preeclampsia was 50 as the study population compared with 50
ladies with normal pregnancy, both were selected at the third
trimester of pregnancy.
Most of the patients were primigravidae in the age group between
25 and 34 years.
The severity of hypertension was graded according to systolic
hypertension group and diastolic hypertension group.
The average value of serum uric acid among the control group
was 4.5 mg/dl compared to 6.5 mg/dl in those patients admitted
as cases of pre-eclampsia. The rising level of serum uric acid was
well correlated with the severity of hypertension. The level of
serum uric acid in between the groups (as mild, moderate and
severe pre-eclampsia) had a P value of 0.016 which is significant.
2002.
.
:
-1
.
-2
.
.
25 34.
4.5
. 6.5
.
.
Abbreviations
AMP
Adenosine Monophosphate
DBPG
DNA
FHR
HELLP
IDDM
JVP
RNA
SBPG
Ribonucleic Acid
Systolic Blood Pressure Group
List of Tables
Table 1:
24
Table 2:
25
group
Table 3:
Table 4:
Table 5:
28
List of Figures
Figure 1:
Figure 2:
29
30
Figure 3:
31
Figure 4:
32
INTRODUCTION
Uric acid is the end result of purine catabolism in man.
The degradation of purine nucleotides (Adenosine, Guanosine
and
Hypoxanthine
monophospates)
and
bases
(adenine,
LITERATURE REVIEW
1-1. Introduction
Pre-eclampsia / eclampsia is an unpredictable multi-organ disorder
unique to human pregnancy. It is associated with significant fetal and
maternal morbidity worldwide. The exact etiology of it is unknown.
Changes such as increased sensitivity to vasopressors, reduced volume,
altered proximal tubular function, and activation of coagulation system
antedate overt hypertension, and suggest that hypertension may not be
central to the pathogenesis of pre-eclampsia.
1-2. Definition
Pre- eclampsia is a syndrome (group of symptoms and signs), which
can be recognized, but not diagnosed because there is no specific
diagnostic test. The presentation is very variable, and although
hypertension and proteinuria are the two signs most easily detected,
they are not central to the pathogenesis of the disorder. No single
feature is consistently present, 20% of women with pre- eclampsia are
normotensive and 30% have no premonitory proteinuria(3).
A number of classifications for hypertensive disorders in pregnancy
have been proposed. The international society for the study of
hypertension in pregnancy (ISSHP) currently define pre- eclampsia as
the occurrence of hypertension in combination with proteinuria after
twenty weeks gestation in a previously normotensive non-proteinuric
patient. (4).
1.
P.I.H.
2.
Proteinuria .
3.
Generalized oedema.
4.
Hyperuricaemia.
5.
Increased haematocrit.
6.
Thrombocytopenia
7.
8.
9.
Hypocalciuria
10.
11.
12.
2.
3.
2.
3.
4.
Headache.
Scotomata.
Blurring of vision.
Altered consciousness.
5.
Pulmonary oedema/cyanosis.
6.
Epigastric pain.
7.
8.
9.
10.
H ELLP syndrome.
concept
of
normontensive
pre-eclampsia
is
well
concentration
<3mg/dl
and
serum
creatinine
were
similar,
plasma
creatinine
was
able
to
bases
(hypoxanthine,
xanthine
and
uric
acid)
renal
disease
patients,
and
long
interval
from
also
had
an
increased
serum
deoxycytidylate
deaminase.
With serial antenatal observations both serum urate and
deoxycytidylate deaminase increased together as early changes
in the development of pre-eclampsia (1977) (15)
1-12. Plasma urate and
hypertensive pregnancies:
In the year 1976, plasma urate measurements were used as
predictors of fetal death in hypertensive pregnancies. This
relation of plasma urate concentration and blood pressure was
studied in 332 pregnant patients with hypertension. Perinatal
mortality was markedly increased when maternal plasma urate
concentrations were raised(16). generally in association with
severe pre-eclampsia of early onset. Plasma urate was a better
indicator than blood pressure of prognosis for the fetus. Maternal
hypertension, even severe, with out hyperuricaemia, was
associated with an excellent prognosis for the fetus. Conversely
(17)
out
among
seventeen
pre-eclamptic
patients,
22
in
patients
with
chronic
hypertension
and
superimposed pre-eclampsia:
The relation ship of serum urate and plate let count changes in
patients with chronic hypertension who developed superimposed
pre-eclampsia was studied in 1978 in 131 patients. Both urate
and plate let count were measured serially during pregnancy.
(22)
count was seen in 55 women who had border line but consistent
increase in plasma urate concentrations.In 49 women whose
plasma urate concentration remained steady, the plate let count
did not change significantly before delivery. (23).
1-16. Abnormal umbilical artery Doppler ultrasound and serum uric
acid level:
In a study in October 1995, the value of doppler study of the umbilical
artery was assessed in predicting outcome in, pre-eclamptic patients.
Fetal well-being was assessed in 113 women with pre-eclampsia by
weekly performed biophysical profile score and doppler study of the
umbilical artery starting early in the third trimester till delivery.
Last
1-17.
Blood
lactate
level
and
hyperuricaemia
in
pre-
eclampsia:
The relationship of blood lactate to the hyper uricaemia
characteristic of pre-eclampsia was studied in 17 pre-eclamptic,
22 hypertensive , and 13 normal pregnant women, all in the third
trimester. Results showed that serum uric acid is elevated,
OBJECTIVES
1. To determine the average level of serum uric acid among the
study population
2. To determine the value of serum uric acid as an indicator of
severity of pre-eclampsia among the study population.
2-4. Technique:
1- Estimation of Serum Uric Acid.
Serum Uric acid was estimated using colorimetry, the test
sample was obtained as venous blood from the study and control
groups after proper explanation and consent from both groups.
2-4-1. Estimation of Uric acid in blood:Enzymatic colorimetric test: Uricase method
Principle:(26,27,28,29)Uric acid is the end product of purine
metabolism, its quantitation aids in the diagnosis of renal
dysfunction.
Uricase catalyzes the oxidation of uric acid to allantoin
and H202 in the presence of peroxidase (POD), H202 reacts
with
4-minoantipyrine
(4AA)
and
3,5
dichloro
2-4-2. PROCEDURE:
Three test tubes were prepared test, standard and blank. To
each the following were added
TEST
STANDARD
BLANK
0.02
STANDARD 8MG/DL
0.02
DISTILLED WATER
0.02
URIC ACIDREAGENT
SERUM
concentration of Standard
(A test / A STD) X 8
Reference value: male: 3.4 - 7.0 mg /dl
females: 2.4-5.7 mg/dl
4-5.Urine for Protein:Urine for protein: was estimated using sulphosalicylic acid
+,++,+++ according to the intensity of protein coagulation in,
urine following the addition of sulphosalicylic acid.
2-6. Data Collection
Data was collected from in patients and control groups (sample
size was 50 for each group). Using a questionnaire and direct
interview.
Data
include:
Personal
History,
name,
age,
residence,
RESULTS
Figure (1) Shows the distribution of parity among both control
group and study sample. The majority of patients were
primigravidae. In the control group majority of cases with more
than two previous deliveries followed by primigravidae.
Figure (2) Shows the family history of renal disease among
both groups, the majority of both had no family history of renal
diseases. Those with positive family history were 7 in the study
sample and 6 in the control group.
Figure (3) shows the family history of hypertension in both
groups. The majority in both groups had no family history of
hypertension. Those with positive family history were 17 in the
control group and 20 in the study sample.
Figure (4) shows the past history of pregnancy induced,
hypertension (PIH) between patient and control groups. In both
groups the majority had no past history of PIH. Those with
positive past history were 4 in the control group and 15 in the
study sample.
The study sample and control group were distributed according
to their age into below 25 years (18 in the control group 11 in
study sample), between 25 -34 years (27 control group, 26 study
sample), 35 years and above (5 control, 13 study sample) Table
(1).
Table (2) shows the distribution of proteinuria between the two
17
moderate,
and
17had
severe
diastolic
hypertension.
Table (4) The level of Uric acid between groups according to
severity of the blood pressure. P value was found to be
significant 0.016.
Table (5) shows systolic blood group for cross tabulation of
protein in urine.
Those with mild systolic hypertension 7 had mild proteinuria,
those with moderate systolic hypertension; 25 had mild
proteinuria and 3 of them had severe proteinuria. Those with
sever systolic hypertension; 8 had mild proteinuria and 7 had
severe proteinuria.
Table (1):
25 34
35 and
above
18
27
11
26
13
Table (2):
Mild
Severe
50
40
10
urine
Table (3):
Distribution of patients and control group according to classification of severity of hypertension
Type of subject
Control
Patient
SBP groups
DBP groups
SBP groups
DBP groups
Count
Count
Count
Count
Mild
50
50
16
Moderate
28
17
Severe
15
17
Table (4):
Shows the significance of uric acid level between groups according to blood pressure measurements
Some of
df
squares
Mean
Sig.
4.553
.016
square
Between groups
20.623
10.312
Within groups
106.457
47
2.265
Total
127.081
49
Table (5):
Distribution of protein uria between patients with mild and
severe pre-eclampsia
Protein in urine
Total
Mild
Severe
SBP mild
Groups moderate
25
28
Severe
15
Total
40
10
50
DISCUSSION
Pre-eclampsia is a disease which has a significant impact on
both fetal and maternal well being and accounts for a
considerable cause of hospital admission in current obstetric
practice. It is principally a disease of primigravidae at the
extremes of reproductive age. This age distribution is well
correlated with the number of patients in the study sample, as
most of them were primigravidae between the age of 25 -34
years.
This disease which is unique to human pregnancy is a real
dilemma as yet its aetiology is unknown as hypertensive disease
of pregnancy which has led to clinical signs such as hypertension
and protienuria, not merely diagnosing disease but defining it.
in the study sample 17cases had severe systolic hypertension 8
cases of those with severe hypertension had mild proteinuria
(<=+2) and 7 cases had severe proteinuria (>=+3) Table (3) and
in
clinical
practice;
some
cases
with
severe
Concerning the value of serum uric acid among both groups the
average level of serum uric acid among the control group was 4.5
mg/dl compared to 6.5 mg/dl among those with pre-eclampsia as
the study sample. Those with severe hypertension had elevated
levels of serum uric acid compared to those with mild and
moderate hypertension, and this is well correlated with the known
association of hyperuricaemia with pr-eclampsia (5).
CONCLUSION
RECOMMENDATIONS
Pre-eclampsia is a multiorgan disorder whose severity is better assessed
through its effect on target organs.
Assessment include renal and liver function tests and good
fetal monitoring , rather than doing a single test alone.
Estimation of serum uric acid in patients admitted with preeclampsia should be part of the tests done for renal function done
for these patients because it showed a significant value in this
study.
REFERENCES
1.
of
the
pathogenesis
and
consequences
of
24. Rocca- MM ; Said - MS ; Khamis - MY; Ghanem -IA ; Karkour TA . The value of doppler study of the umbilical artery in predicting
perinatal outcome in preeclamptic patients. J - obstet -- Gynaecol .
1995 , Oct ; 21 (5) : 427-31.
Name: . Age:..
Residence:. Occupation:..
Married for:.
G Par+.
LMP EDDGA..
BP: Pre-pregnancy 1st trimester..
Now: BP..
Symptoms:
1. Headache:
Yes..
No..
2. Epigastric pain:
Yes..
No..
3. Blurring of vision:
Yes..
No..
4. Oedema-face:
Yes..
No..
Yes..
No..
L.Limbs:
Yes..
No..
Yes..
No..
1. P.I.H
Yes..
No..
2. Eclampsia
Yes..
No..
1. Pale
Yes..
No..
2. Jaundiced
Yes..
No..
P.H. of:
O/E:
Face:
Yes..
No..
No..
Ascitis:
Yes..
No..
L. Limbs:
Yes..
No..
FL..
Investigation:
1. S. Uric acid.
2. Urine for protein + ++.. >++.