EXAMINATION OF SOME BIOCHEMICAL MARKERS OF NUTRITIONAL POSITION AMONG ADULT SICKLE CELL ANAEMIA PATIENTS IN STEADY STATE IN ZARIA

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EXAMINATION OF SOME BIOCHEMICAL MARKERS OF NUTRITIONAL POSITION AMONG ADULT SICKLE CELL ANAEMIA PATIENTS IN STEADY STATE IN ZARIA

ABSTRACT

Sickle cell anaemia is a chronic haemolytic state which is characterized by hypercatabolism that could predispose to malnutrition. The low socio economic backgroundof our patients may worsen their health status. The study was aimed atassessing some biochemicalmarkers of nutritional status among adult sickle cell anaemia patients in steady state in Zaria. It is a crosssectional descriptive study which was conducted in the Departments of Chemical Pathology and Haematology, Ahmadu Bello University Teaching Hospital, Shika, Zaria, Kaduna State.  Some biochemical markers of nutritional status of 60 adult SCA patients in steady state and 60 healthy non SCA controls were assessed. Mean (±SEM) serum vitamin D concentration was significantly lower in SCA patients 14.55±1.49 ug/L compared with controls 25.87.±4.29 ug/L (p<0.05). Mean (±SEM) serum calcium concentration was significantly lower in SCA patients 2.20 ±0.06 mmol/L compared with controls2.33±0.04 mmol/L (p<0.05).Mean (±SEM) serum albumin concentration was significantly lower in SCA patients 33.40±1.66 g/L compared with controls 40.13.±0.85 g/L (p<0.05).Mean (±SEM) serum inorganic phosphate concentration was significantly higher in SCA patients2.00.±0.13 mmol/L compared with controls 1.26±0.08 mmol/L (p<0.05).The mean (±SEM)BMI Kg/m2 was significantly lower in SCA patients 21.37±0.35 Kg/m2 compared with controls 23.27 Kg/m2 (p<0.05). The study also showedno correlations between BMI and the biochemical markers measured in both SCA patients and controls.

In conclusion, mean sera concentrations of vitamin D, calciumand albuminamong adult SCA patients in steady state were lowcompared with controls, so also BMI. The meanserum concentration of inorganic phosphate however, was significantly higher in SCA than in the control subjects.  There wereno correlations between BMI and biochemical markers measured in thestudy population. Therefore SCA patients in steady state are more malnourished when compared to the controls.

 

 

 

TABLE OF CONTENT

Page

Title page………….…………………………………..……….………………..…….………. i

Declaration……………………………………………………………………….………         ii

Certification …………………………………………………………..…… ……………… iii

Acknowledgements……………………………………………………………………….          iv

Abstract…………………………………………………………………………… ………v Table of contents…………………………………………………………… ………………vi

List oftables..…………………………………………………………………….……….         x

List offigures……………………………………………………………………..…..….          xi

Abbreviations/Symbols used…………………………………………..………………..           xii

1.0             CHAPTER ONE: INTRODUCTION.…………………………………………. 1

1.1            Background…………………………………………………..……………………. 1

1.2    Statement of the problem…………………………………………………………. 2

1.3    Justification……………………………………………….………………………. 3

1.4    Aim and objectives…………………………………………………………..…… 3

1.5    Research question/Hypothesis…………………………………………………….. 4

2.0             CHAPTER TWO: LITERATURE REVIEW………………………………… 5

2.1             Sickle cell anaemia………………………………………………………………. 5

2.1.1 Historyof Sickle Cell anaemia….………………………………………………………                  5

2.1.2  Epidemiology of Sickle cell disease……………………………………………..           5

2.1.3  Pathophysiology of Sickle cell anaemia…………………………………………            6

2.1.4  Clinical Features……………………………………………………………..….             9

2.1.4.1 General Features………………….……………………………………………..           9

2.1.4.2 Painful Crises……………………………………………………………………          9

2.1.4.3 Infections…………………………………………………………..……………            10

2.1.5  Effects on major organ systems…………`………………………………………           10

 

2.1.5.1 The Respiratory System………………………………………………………          10

2.1.5.2 The Cardiovascular system……………………………………………….….          11

2.1.5.3 The liver and spleen…………………………………………………………..          11

2.1.5.4 The Musculoskeletal System……..………………………………….………            11

2.1.5.5 The Nervous System………………………………………………………….          12

1.5.6 The Genito-Urinary system……………………………………………………          12

2.1.6  Sickle Cell anaemia and Nutrition……………………………………………           13

2.1.6.1 SCA and Undernutrition…….……………………………………………….            14

2.1.6.2 Effect of Infection on nutrition in SCA……………………………….         ..….     16

2.1.6.3 Implications for growth and maturation abnormality in SCA…………… …….     16

2.1.6.4 Nutritional intervention in management of SCA……………………..…..                17

2.1.7  Diagnosis of Sickle Cell Disease……………………………………………..          18

2.1.7.1 Laboratory Diagnosis…………………………………………………………          18

2.1.7.1.1Haemoglobin sickling test………………………………………     ………….… 18

2.1.7.1.2Haemoglobin solubility test…………………………………………………          18

2.1.7.1.3Haemoglobin electrophoresis………………………………………………..         19

2.1.7.1.4 Isoelectric focusing………………………………………………………..…       19

2.1.7.1.5 High Performance Liquid Chromatography………………………………..          20

2.1.7.1.6DNA analysis…………………………………………………………………        20

2.1.8 Samples used in antenatal Diagnosis…………………………………………           21

2.1.8.1 Foetal blood sampling…………………………………………………….…           21

2.1.8.2 Chorionic villi or amniotic cell DNA……………………………………….            22

2.1.9 Treatment of sickle cell anaemia……………………………………………             22

2.1.9.1 Drug treatments…………………………………………………….………             22

2.1.9.1.1Hydroxyurea………………………………………………………………..           23

2.1.9.2 Transfusion………………………………………………………………… 23

2.1.9.3 Bone Marrow or Stem Cell Transplantation…………………………………          24

2.2         Methods for assessing nutrition………………………………………………..… 25

2.2.1  Clinical observation and examination……………………………………………………….         25

2.2.2  Anthropometric measurement………………………………………………….        26

2.2.3 Dietary history…………………………………………………………………… 26

2.2.4  Biochemical methods……………………………………………………………        26

2.3       Vitamin D……………………………………………………………………….      28

2.3.1 Vitamin D metabolism…………………………………………………………         28

2.3.2 Mechanism of action…………………………………………………………..          29

2.3.3 Functions of vitamin D………………………………………………………..          30

2.3.4 Vitamin D deficiency………………………………………………………….          33

2.3.5 Risk factors for vitamin D deficiency…………………………………………..        35

2.3.6 Assessing vitamin D nutritional status in SCA………………………………            39

2.3.6.1Vitamin D assay……………………………………………………………            39

2.3.6.2 Extraction and Deproteinization……………………………………….       ……    40

2.3.6.3 Column Chromatography………………………………………………………        43

2.3.6.4Measurement of 25-Hydroxyvitamin D…………………………      ……………    43

2.3.6.5Measurement of 1,25-Dihydroxyvitamin D………………………………     …….. 43

2.3.6.6Radioreceptor Assay…………………………….……………………………….      44

2.3.6.7Radioimmunoassay………………………………………….…………………..      44

2.3.6.8 Specimen Requirements……………………………………………………..…       44

2.4Albumin………………………………………………………………………….            45

2.4.1 Synthesis of albumin……………………………………………………………         46

2.4.2 Degradation of albumin…………………………………………..…………….        47

2.4.3Role of albumin in maintaining microvascular integrity………………….… 47

2.4.4 The prognostic value of serum albumin…………………………………………      48

      3.0       CHAPTER THREE: MATERIALS AND METHODS…….……………….…. 50

3.1     Study area……………………………………………………………………..          50

3.2            Study population and Design……………………………………………..                50

3.2.1  Inclusion criteria…………………………………………………………….                   51

3.2.2   Exclusion criteria…………………………………………………………….                51

3.2.3   Informed Consent………………………………………………………….                    51

3.2.4 Ethical consideration…………………………………………………………                   51

3.2.5   Sample size determination..……………………………………….………….                 52

3.3     Sampling technique…………………………………………..………….……                  53

3.4     Blood collection and processing……………………………..……….………                 54

3.5     Chemicals……………………………………………………………….…….                 54

3.6     Equipment……………………………………………………………………                 54

3.7 Quality control………………………………………………………..………                      54

3.8    Analytical methods…………………………………………………………                    55

3.8.1 Measurement of serum Vitamin D…………………………………………                     55

3.8.2 Measurement of serum calcium……………………………………………                     56

3.8.3 Measurement of serum phosphate…………………………………………..                    57

3.8.4 Measurement of serum albumin…………………………………………..                       58

3.9            Statistical analysis…………………………………………………………….         59

4.0           CHAPTERFOUR: RESULTS…………………………………………………… 60

5.0 CHAPTER FIVE: DISCUSSION……………………………………………… 66 6.0    CHAPTER SIX:  CONCLUSION AND RECOMMENDATION…………… 69

6.1             CONCLUSION………………………………………………………………..… 69

6.2             RECOMMENDATIONS……………………………………………………….. 69

REFERENCES………………………………….……………………………………             70

APPENDICES………………………………………………………………………… 92         LIST OF TABLES

Table Page

4.1       Anthropometric characteristics ofthe study population ………………..….                61

4.2       Some biochemical markers of nutritional status in the study population…..             62

4.3       Correlationsbetween BMI and some markers of nutritional statusamong

adult SCA patientsin steady state………………………………………….              63

4.4  Correlations between BMI and some markers of nutritional status in control……   64 LIST OF FIGURES

 

FigurePage

2.1   Picture showing sickled red blood cells…………………………………..…………….…8

2.2   Diagram showing synthesis of vitamin D…………………………………………….…..41 2.3   Diagram showing calcium and phosphate regulation…………………………………….42 ABBREVIATIONS AND SYMBOLS

 

AA               Atomic Absorption
AAS               Atomic Absorption spectroscopy
ABU               Ahmadu Bello University
ABUTH                 Ahmadu Bello University Teaching Hospital
ACS Acute chest syndrome
ALB   Albumin
 ARDs   Acute Respiratory syndromes
ATP     Adenosine triphosphate
AVN     Avascular necrosis
BCG       Bromocresol Green
BMD       Bone mineral density
BMI       Body mass index
BMT       Bone marrow transplant
CA       Cellulose acetate
Ca2+       Calcium ions
cAMP       Cyclic Adenosine monophosphate
CDC       Centre for disease control
cGMP       Cyclic Guanosine monophosphate
CLSI       Clinical Laboratory and Standards Institute
cm/s       centimetre per second
CPBA       competitive protein binding assay
CPC       CresolphthaleinComplexone
DBP       Diastolic blood pressure

 

 

DNA   Deoxynucleic acid
EDTA   Ethylinediaminetetraacetic acid
eg.   Example
etc.   etcetera
EIA   Enzyme imminoabsorbant
ELISA   Enzyme-linked ImmunoSorbent assay
et al   And others
FGF   Fibroblast growth factor
Fig.   Figure
Gc-globlin   Group-specific component globulin
GFR   Glomerular filtration rate
GIT   Gastrointestinal tract
Hb     Haemoglobin
HbA     Haemoglobin A
HbF     Haemoglobin F
HbPhiladelphia     Haemoglobin Philadelphia
HbS     Haemoglobin S
HbS Lep B     Haemoglobin S Lepore
HbS O Arab     Haemoglobin S O Arab
HbSC     Haemoglobin SC
HbSD     Haemoglobin SD
HbSD Punjab     Haemoglobin SD Punjab
HbSE     HaemoglobinSE
HbSS     Haemoglobin SS
HIV     Human immune deficiency virus
HPLC     High performance liquid chromatography
ICMA     Immunochemiluminescence assay

ID-MS                                                 isotope dilution-mass spectrometry

IEF                                                      Isoelectric focusing

IL                                                        Illinois

Invitro                                                 Outside body

Invivo                                                  Inside body

ISEs                                                     Ion selective electron

IU                                                        International unit

KDa                                                     kilodalton

Kg                                                        kilogramme

Kg/m2                                                  Kilogramme per metre square

Km                                                      Kilometre

LCMS                                             liquid chromatography-mass spectrometry LDH                                       Lactate dehydrogenasem mg/dl                                          milligramme per deciltre

ml                                                         milliliter

MAPK                                                 mitogen-activated protein kinase

mmHg                                             Millimetre of mercury mmol/L                                          millimole per litre

mol                                                      mole

n                                                          Sample size

NADP                                             nicotinamide-adenine dinucleotide phosphate ng/ml                                             nanogramme per millilitre

nm     nanometre nmol     nanomole

NO                                                      Nitric oxide

NSAID                                                Non steroidal anti-inflammatory drug

NW                                                     Normal weight

0c                                                         Degree Celsius

P                                                          Probability

PCR                                                Polymerase chain reaction pH                                            -log of hydrogen ion concentration

PO32+                                                 Phosphate ions

PTH                                                     Parathyroid hormone

RANKL                                              Receptor activator of nuclear factor-kBligand,

RBC                                                    Red blood cell

RCTs                                                   Randomized controlled trials

RFLP                                                    Restriction fragment length polymorphism

RIA                                                     Radioimmunoassay

RNA                                                    Ribonucleic acid

rpm                                                             revolution per minutes RRA                                  Radioreceptor Assay

SBP                                                     Systolic blood pressure

SCA                                                    Sickle cell anaemia

SCD                                                    Sickle cell disease

SEM                                                    Standard error of mean

SNPs                                                    Single nucleotide polymorphisms

SPSS                                               Statistical Package for the Social Science TAMV                                     Time-average mean velocity u                                                       micro

ug/L                                                            microgramme per litre umol/L                                            micromol per litre

UV                                                      Ultra violet

UVB                                                    Ultra violet B

VCAM -1                                            vascular cell adhesion molecule 1

VD2     Vitamin D 2
VD3     Vitamin D 3
VDBP     Vitamin D binding protein
VDR     Vitamin D receptor
VTD     Vitamin D
VTDD       Vitamin D deficiency
WBC       White blood count
WHO       Whole Health Organization
α       Alpha
γ       Gamma
δ       Delta
α-       Alpha thalassaemia gene (minor)
α+       Alpha thalassemia gene (major)
β       Beta
β-       Beta thalassemia gene (minor)
β+       Beta thalassemia gene (major)
%       Percent
±     Plus or minus
    Equal to or less than
    Equal to greater than
<     Less than
>     Greater than
    Approximately

 

 

 

 

CHAPTER ONE

1.0 INTRODUCTION

1.1 BACKGROUND OF THE STUDY

Sickle cell anemia (SCA) is a genetic disease that results from the substitution of valine for glutamic acid in the β-globin chain of the hemoglobin molecule (Pauling and Itano, 1949). The consequence of this amino acid substitution is the formation of hemoglobin S (HbS). Under low oxygen tension and/or conditions of acidosis. HbS precipitates and forms polymerized crystals called tactoids (hemoglobin polymers), which distort the red blood cells (Nelson and Cox, 2005; Ganong, 2003). The resulting sickle-shaped red cells lose their pliability and cannot navigate the small capillaries, become sticky, and adhere to the small veins, small arteries, and other blood vessels causing vaso-occlusion (Aster, 2005; Bunn and Forget, 1977). In addition, red blood cells homozygous for HbS (HbSS) are susceptible to premature destruction, with a red blood cell life span of 8–25 days as compared to 100–120 days for normal red blood cells (Solankiet al, 1988).

In the last few decades, studies have documented the presence of micro- and macronutrient deficiency among individuals with SCA and their possible association with immunologic, nutritional and growth abnormalities (Heymanet al.,1985; Gray et al., 1992; Serjeant et al., 2001). Patients with sickle cell anemia (SCA) have low bone mass compared to healthy subjects (Lalet al, 2006). Low bone mass in these patients is apparent even after adjusting for age, height, pubertal development, and lean body mass, suggesting that the deficits cannot be fully explained by short stature, delayed puberty, or altered body composition. Chronic haemolytic anemia and the resulting erythroblastic hyperplasia may contribute to bone demineralization in SCA (Serjeant and Serjeant, 2001). Furthermore, reduced physical activity, decreased circulating growth hormone, vitamin D deficiency and poor dietary intake of bone-forming nutrients   are likely contributing factors (Buisonet al, 2004). Suboptimal peak bone mass acquisition in childhood may contribute to the development of osteoporosis in later life (Heanyet al, 2002).

Studies using direct measure of nutritional status (Enwonwu and Lu, 1991; Gray et al., 1992; Kennedy et al., 2001), indirect assessment of nutritional status (Henderson et al., 2005), and application of nutritional supplementation (Prasad and Cossack, 1984, Heymanet al., 1985), have established the association between SCA and the presence of nutritional deficiency among patients with the disease. These studies showed that although intake might be sufficient when measured against the recommended daily dietary allowance for age and sex, it is still insufficient for the individual with SCA due to the increased nutritional demand imposed by the disease. The result was the manifestation of malnutrition-like features (Prasad, 1997; Al-Saqladiet al, 2008; Hyacinth, et al, 2010).

1.2 STATEMENT OF THE PROBLEM

Nutritional deficiencies have not been given serious consideration in the assessment of SCA patients in this environment. It will be essential for physicians to adopt a nutritional approach as a part of the management modality for SCA in the light of the fact that more than two-thirds of the patients with SCA live in areas with low socioeconomic status and have little to no means of accessing the current methods of management. Therefore the present study is aimed at assessing some biochemical

markers of nutritional status in this group of patients.

                      1.3       JUSTIFICATION OF THE STUDY

The assessment of nutritional status in SCA patients could improve in the management of their conditions.  

                      1.4       AIM AND OBJECTIVES OF THE STUDY

                  Aim

To assess some biochemical markers of nutritional status among adult SCA patients in steady state in Zaria.

                  Objectives

The objectives of this study were as follows:

  1. To determine serum levels of vitamin D, calcium, phosphate and albumin in adult SCA patients in steady state in Zaria and HbAA controls.
  2. To compare the serum levels of vitamin D, calcium, phosphate and albumin obtained from adult SCA patients in steady state and apparently healthy non SCA HbAA controls.
  3. To determine the anthropometric parameters of adult SCA patients in steady state and HbAA controls.
  4. To correlate the anthropometric parameters with serum levels of vitamin D, calcium, phosphate and albumin obtained from the study population.

                      1.5       RESEARCH HYPOTHESIS

H0: Sickle cell anaemia does not affect nutritional status (Null hypothesis).

H1: Sickle cell anaemia affects nutritional status (Alternate hypothesis).

EXAMINATION OF SOME BIOCHEMICAL MARKERS OF NUTRITIONAL POSITION AMONG ADULT SICKLE CELL ANAEMIA PATIENTS IN STEADY STATE IN ZARIA

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