RENAL BIOCHEMICAL CHANGES OF PREGNANCY-INDUCED HYPERTENSION IN PREGNANT WOMEN ATTENDING TERTIARY HOSPITALS IN ENUGU STATE

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ABSTRACT
Pregnancy induced hypertensive disorders have become very common medical complication in Nigeria with its attendant morbidity and mortality. The morbidity and mortality may be associated with its possible effect on the kidneys which was studied. Results of the electrolyte changes from this study showed that there was non-significant difference (p>0.05) in sodium ion concentration of subjects with pregnancy induced hypertension in second and third trimesters (groups 4 and 5 respectively) compared with the control groups (groups 1,2,and 3) who are non-hypertensives in first, second and third trimesters respectively. Similarly, the potassium ion (K+) concentration showed non-significant difference (p>0.05) between the groups 4 and 5 and the control groups even though the highest concentration of potassium ion was seen in the group 4 subjects. From the study, chloride ion (Cl-) and bicarbonate ion (HCO3-) were found to have no significant difference (p>0.05) in concentration between groups 4 and 5 and the control groups. From the estimation of urea and creatinine, it was found that there was no significant difference (p>0.05) in the urea and creatinine concentration between the hypertensives and normotensives in different trimesters however it was found that both urea and creatinine increased in the third trimesters in the hypertensive. The total protein, albumin and globulin level of the subjects in groups 4 and 5 were found to decrease significantly (p<0.05) compared to the control subjects in the corresponding trimesters.

TABLE OF CONTENTS

Title Page … … … … … … … … … … i
Certification … … … … … … … … … … ii
Dedication … … … … … … … … … … iii
Acknowledgements … … … … … … … … … iv
Abstract … … … … … … … … … … v
Table of Contents … … … … … … … … … vi
List of Figures … … … … … … … … … … xii
List of Tables … … … … … … … … … … xiv
List of Abbreviations … … … … … … … … … xv

CHAPTER ONE: INTRODUCTION
1.1 Hypertension………………………………………………………………………………………………….2
1.1.1 Primary(essential) hypertension………………………………………………………………………..2
1.1.1.1 Classification of primary hypertension………………………………………………………………3
1.1.1.2 Risk factors for primary hypertension………………………………………………………………. 4
1.1.2 Secondary hypertension …………………………………………………………………………………. 7
1.1.2.1 Risk factors for secondary hypertension …………………………………………………………… 7
1.1.3 Pathophysiology of hypertension …………………………………………………………………….11
1.1.4 Abnormalities of the sympathetic nervous system ……………………………………………..12
1.1.5 Diagnosis of hypertension ………………………………………………………………………………13
1.1.6 Epidemiology of hypertension ……………………………………………………………………….. 14
1.1.7 Complications of hypertension ……………………………………………………………………….. 14
1.2 Pregnancy ……………………………………………………………………………………………………. 15
1.2.1 Fertilisation …………………………………………………………………………………………………. 16
1.2.2 Diagnosis of pregnancy ………………………………………………………………………………….18
1.2.3 Signs of pregnancy………………………………………………………………………………………….19
1.2.4 Physiology of pregnancy …………………………………………………………………………………19
1.2.5 Hypertension in pregnancy …………………………………………………………………………….. 21
1.2.5.1 Pregnancy-induced hypertension………………………………………………………………………21
1.2.5.2 Gestational hypertension …………………………………………………………………………………21
1.2.5.3 Preeclampsia …………………………………………………………………………………………………21
1.2.5.4 Eclampsia ……………………………………………………………………………………………………..22
1.2.6 Risk factors associated with hypertension in pregnancy ………………………………………22
1.2.7 Aetiopathological factors for preeclampsia ………………………………………………………..22
1.2.7.1 Placental ischaemia/hypoxia and the aetiology of preeclampsia ………………………….. 22
1.2.8 Complication of pregnancy-induced hypertension ………………………………………………24
1.2.9 Justification for the research …………………………………………………………………………….25
1.2.10 Aim and objectives of the study ………………………………………………………………………..25
1.2.10.1 Aim of the study ……………………………………………………………………………………………. 25
1.2.10.2 Specific objectives of the study ……………………………………………………………………….. 25

CHAPTER TWO: MATERIALS AND METHODS
2.1 Materials ………………………………………………………………………………………………………26
2.1.1 Instruments and Equipments ……………………………………………………………………………26
2.1.2 Chemicals/Reagents ……………………………………………………………………………………….26
2.1.3 Samples ………………………………………………………………………………………………………..26
2.2 Methods … …………………………………………………………………………………………………… 27
2.2.1 Experimental Design …………………………………………………………………………………….. 27
2.2.2 Determination of sodium ion concentration ………………………………………………………27
2.2.3 Determination of potassium ion concentration …………………………………………………..28
2.2.4 Determination of chloride ion concentration ……………………………………………………..29
2.2.5 Determination of bicarbonate ion concentration ………………………………………………..30
2.2.6 Determination of creatinine concentration ………………………………………………………..30
2.2.7 Determination of urea concentration ………………………………………………………………..32
2.2.8 Determination of total protein concentration ……………………………………………………. 33
2.2.9 Determination of albumin concentration …………………………………………………………..34
2.3 Statistical analysis …………………………………………………………………………………………35

CHAPTER THREE: RESULTS
3.1 Sodium ion concentration of normotensive and hypertensive subjects
in different trimesters in Enugu metropolis………………………………………………………..36
3.2 Potassium ion concentration of normotensive and hypertensive subjects
in different trimesters in Enugu metropolis ……………………………………………………….38
3.3 Chloride ion concentration of normotensive and hypertensive subjects
in different trimesters in Enugu metropolis ……………………………………………………….40
3.4 Bicarbonate ion concentration of normotensive and hypertensive subjects
in different trimesters in Enugu metropolis ……………………………………………………….42
3.5 Urea concentration of normotensive and hypertensive subjects in different
trimesters in Enugu metropolis ………………………………………………………………………..44
3.6 Creatinine concentration of normotensive and hypertensive subjects in
different trimesters in Enugu metropolis …………………………………………………………..46
3.7 Total protein concentration of normotensive and hypertensive subjects in
different trimesters in Enugu metropolis …………………………………………………………..48
3.8 Albumin concentration of normotensive and hypertensive subjects in different
trimesters in Enugu metropolis ………………………………………………………………………..50
3.9 Globulin concentration of normotensive and hypertensive subjects in
different trimesters in Enugu metropolis …………………………………………………………..52

CHAPTER FOUR: DISCUSSION ….. …. ….. …. … … 54
4.1 Discussion … … … … … … … … … 54
4.2 Conclusion … … … … … … … … … 56
REFERENCES … … … … … … … … … 58
APPENDICES … … … … … … … … … 63

LIST OF FIGURES

Fig. 1: Pathophysiology of hypertension … … … … … … 11

Fig. 2: Complications of hypertension … … … … … … 14

Fig. 3: Stages of human embryogenesis … … … … … … 15

Fig. 4: Fertilization and implantation in humans … … … … … 16

Fig. 5: Pathways by which reduced uterine perfusion pressure and placenta ischaemia
may lead to endothelial and cardiovascular dysfunction … … … 22

Fig. 6: Sodium concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 36

Fig. 7: Potassium concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 38

Fig. 8: Chloride ion concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 40

Fig. 9: Bicarbonate concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 42

Fig. 10 Urea concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 44

Fig. 11: Creatinine concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 46

Fig. 12: Total protein concentration of normotensive and hypertensive
pregnant subjects in different trimesters in Enugu metropolis … … 48

Fig. 13: Albumin concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 50

Fig.14: Globulin concentration of normotensive and hypertensive pregnant
subjects in different trimesters in Enugu metropolis … … … 52

LIST OF TABLES

Table 1: Classification of primary hypertension … … … … … 3

Table 2: Reagent concentrations for determination of total protein concentration … 33

Table 3: Reagent mixture and order of addition for the determination
of albumin concentration … … … … … … … 34

LIST OF ABBREVIATIONS
LNMP Last normal menstrual period
PIH Pregnancy induced hypertension
RAS Renin-angiotensin system
ADH Antidiuretic hormone
ACTH Adrenocorticotrophic hormone
ACE Angiotensin converting enzyme
ARBS Angiotensin receptor blockers
CT SCAN Computer tomography scan
MRI Medical resonance imaging
NSAID Nonsteroidal anti-inflammatory drug
MDRD Modification of diet in renal disease
GFR Glomerular filtration rate
ECG/EKG Electrocardiogram
HCG Human chorionic gonadotrophin
SFIT-1 Soluble fms-like tyrosine kinase-1
ANG II Angiotensin 2
RUPP Reduced uterine perfusion pressure
TX Thromboxane
ROS Reactive oxygen species
NO Nitric oxide
ET-1 Endothelin-1
TPR Total peripheral resistance
VEGF Vascular endothelial growth factor
PIGF Placental growth factor
CVA Cerebrovascular accident
DIC Disseminated intravascular coagulation
CI- Chloride ion
HCO3- Bicarbonate ion
Na+ Sodium ion
K+ Potassium ion

CHAPTER ONE
INTRODUCTION

Hypertension is a multi-factorial process prevalent in both developed and developing countries with a common end result of elevated blood pressure (Wu et al., 2009). Hypertension affects 25% of adults in resource-rich countries (Pierdomenico et al., 2009). If untreated, it carries a high mortality rate. Risk factors for hypertension include family history, race (most common in blacks), stress, obesity, a diet high in saturated fats or sodium, tobacco use, sedentary lifestyle, and aging (Pierdomenico et al., 2009). Hypertension is more prevalent among adults between 35 – 60 years of age and could lead to cardiovascular disease (Pierdomenico et al, 2009).
Human pregnancy is the carrying of one or more offsprings, known as fetus or embryo, in the womb of a woman. In pregnancy, there can be multiple gestations, as in the case of twins or triplets. Childbirth usually occurs about 38 weeks after conception; in women who have a menstrual cycle length of four weeks, this is approximately 40 weeks from the last normal menstrual period (LNMP).
Pregnancy induced hypertension is the most common medical complication of pregnancy ( Hjartardottir et al., 2004). Pregnancy-induced hypertension (PIH) is defined as a rise in blood pressure above 140/90mmHg on two or more occasions, at least 6 hours apart during pregnancy. It occurs in the second half of pregnancy (usually after 20 weeks of gestation) in a woman who previously had normal blood pressure (Zhang, 2007). Pregnancy-induced hypertension affects 10% of pregnancies, and pre-eclampsia complicates 2–8% of pregnancies. Eclampsia occurs in about 1/2000 deliveries in resource-rich countries. In resource-poor countries, estimates of the incidence of eclampsia vary from 1/100–1/1700 . Pregnancy induced hypertension is associated with high blood pressure, oedema and proteinuria (Vintch et al., 2008)

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