CHAPTER ONE

INTRODUCTION AND LITERATURE REVIEW

1.1 BACKGROUND OF THE STUDY

Hypertension, commonly known as high blood pressure, is a global health concern

affecting millions of individuals worldwide. Hypertension can be primary, which may
develop as a result of environmental or genetic causes, or secondary, which has
multiple etiologies, including renal, vascular, and endocrine causes. Primary or
essential hypertension accounts for 90-95% of adult cases, and a small percentage of
patients (2-10%) have a secondary cause. Hypertensive emergencies are most often
precipitated by inadequate medication or poor adherence. Hypertension develops
secondary to environmental factors, as well as multiple genes, whose inheritance
appears to be complex. Obesity, diabetes, and heart disease also have genetic
components and contribute to hypertension. Epidemiologic studies using twin data
and data from Framingham Heart Study families reveal that blood pressure (BP) has a
substantial heritable component, ranging from 33% to 57%. In an attempt to elucidate
the genetic components of hypertension, multiple genome wide association studies
(GWAS) have been conducted, revealing multiple gene loci in known pathways of
hypertension as well as some novel genes with no known link to hypertension as of
yet. The biochemical estimation of sodium (Na+) and chloride (Cl-) levels in
hypertensive subjects plays a crucial role in understanding the underlying mechanisms
contributing to hypertension and guiding appropriate treatment strategies (Brown et
al., 2015).

Sodium is a vital electrolyte that plays a key role in maintaining fluid balance, nerve
function, and muscle contraction in the body. However, excessive sodium intake can
lead to fluid retention, increased blood volume, and elevated blood pressure, thereby
contributing to the development and progression of hypertension. By accurately
measuring Na+ levels in hypertensive individuals, healthcare providers can assess
their sodium status, monitor electrolyte imbalances, and tailor dietary
recommendations to help manage hypertension effectively.
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Chloride is an essential electrolyte that works in tandem with sodium to regulate fluid
balance and acid-base equilibrium in the body. Abnormal Cl- levels have been
associated with various health conditions, including hypertension. By evaluating Cl-
concentrations in hypertensive subjects, clinicians can gain insights into their
electrolyte status, assess renal function, and identify potential risk factors contributing
to elevated blood pressure.

Biochemical estimation of Na+ and Cl- levels in hypertensive subjects provides

valuable information for healthcare professionals to optimize treatment approaches,
monitor disease progression, and mitigate cardiovascular complications associated
with hypertension. By elucidating the intricate interplay between these electrolytes
and hypertension, researchers can advance our understanding of the pathophysiology
of high blood pressure and contribute to the development of targeted therapies to
improve patient outcomes and overall cardiovascular health.

1.2 JUSTIFICATION OF STUDIES

The study on the biochemical estimation of sodium (Na+) and chloride (Cl-) levels in
hypertensive subjects in justification explains that sodium and chloride are key
electrolytes that play essential roles in maintaining normal physiological functions in
the body, including fluid balance, nerve conduction, and muscle function.
Dysregulation of these electrolytes, particularly in the context of hypertension, can
have significant implications for cardiovascular health and overall well-being.
Hypertension is a prevalent and serious medical condition that affects a large portion
of the global population. By investigating the levels of Na+ and Cl- in hypertensive
individuals, researchers can uncover potential mechanisms underlying the
development and progression of high blood pressure. Studying this can help guide the
development of more targeted treatment approaches and interventions to better
manage hypertension and its associated complications (Brown et al., 2018)

Biochemical estimation of Na+ and Cl- in hypertensive subjects can provide valuable

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insights into the impact of dietary habits, fluid intake, and medication regimens on
electrolyte balance and blood pressure control. By understanding the relationship
between these electrolytes and hypertension, healthcare professionals can tailor more
personalized and effective management strategies for individuals with high blood
pressure. In conclusion, the study of Na+ and Cl- levels in hypertensive subjects is not
only scientifically justified but also holds significant clinical relevance for improving
patient care and outcomes in the management of hypertension (Castejon et al., 2021)

1.3 AIMS AND OBJECTIVES:

Aim

The aims of studying the biochemical estimation of Na+ and Cl- in hypertensive
subjects include understanding electrolyte balance in hypertension, identifying
potential mechanisms of high blood pressure development, and informing
personalized treatment strategies for better management of hypertension and its
complications.

Objectives

1. To determine the levels of sodium (Na+) and chloride (Cl-) in hypertensive

individuals.

2. To assess the correlation between Na+ and Cl- levels and blood pressure in
hypertensive patients.

3. To investigate any potential imbalances in Na+ and Cl- in hypertensive

subjects.

4. To identify any associations between Na+ and Cl- levels and hypertensive
complications.

5. To explore the impact of Na+ and Cl- regulation on hypertension

management.

6. To determine the effectiveness of controlling Na+ and Cl- levels in managing

hypertension.
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 7. To contribute to the development of personalized treatment approaches based
on Na+ and Cl- levels in hypertensive individuals.

1.4 STATEMENT OF PROBLEM

Here are the challenges faced in studying the Biochemical estimation of Na+and Cl in
hypertensive subject

Sample Contamination: Contamination can occur during sample collection,

handling, or processing, leading to inaccurate results. This could skew the findings
and compromise the integrity of the study.

Inconsistent Sample Collection: Obtaining consistent and reliable samples from

hypertensive individuals was a challenge. Factors such as variations in sample
collection techniques, timing of sample collection, and individual variability can
impact the accuracy and reliability of the results. Standardizing sample collection
procedures to minimize variability is crucial.

Confounding Variables: This confounding variables affects the biochemical

estimation of Na+ and Cl- in hypertensive subjects. Factors such as medications, diet,
hydration status, and underlying health conditions can all influence Na+ and Cl-
levels. Controlling for these variables is essential to draw accurate conclusions from
the study.

Analytical Variability: Analyzing Na+ and Cl- levels in biological samples involves
complex laboratory techniques that can introduce analytical variability. Issues such as
calibration errors, equipment malfunction, and assay variability impacted the accuracy
and reliability of the results. Implementing quality control measures and ensuring
standardized laboratory protocols are essential to minimize analytical variability.

Data Interpretation: Interpreting the biochemical estimation data of Na+ and Cl- in
hypertensive subjects was also challenging, especially when considering the intricate
interplay between these electrolytes and hypertension. Understanding the significance
of the findings, interpreting the results in the context of other biochemical parameters,
and drawing meaningful conclusions require specialized knowledge and expertise.
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Ethical Considerations: Conducting studies on hypertensive subjects for biochemical
estimation of Na+ and Cl- raises ethical considerations related to subject safety,
informed consent, and data privacy. Ensuring that the study adheres to ethical
guidelines, obtaining informed consent from participants, and protecting their
confidentiality are critical aspects that need to be addressed throughout the research
process.

1.5 LITERATURE REVIEW

Hypertension, a prevalent cardiovascular risk factor worldwide, has been extensively

studied in relation to electrolyte imbalances, particularly sodium (Na+) and chloride
(Cl-). The biochemical estimation of Na+ and Cl- in hypertensive subjects plays a
crucial role in understanding the pathophysiology and management of this condition.
Numerous studies have shed light on the intricate relationship between electrolyte
levels and hypertension. Research has shown that hypertensive individuals often
exhibit dysregulation of Na+ and Cl- homeostasis, which can contribute to the
development and progression of hypertension. High Na+ intake has been associated
with increased blood pressure, while low dietary Cl- intake has been linked to elevated
renin levels and hypertension. These findings underscore the importance of
monitoring Na+ and Cl- levels in hypertensive patients to optimize treatment
strategies. Electrolyte imbalances, particularly Na+ and Cl-, have been implicated in
the pathogenesis of hypertensive complications such as cardiovascular diseases, renal
dysfunction, and electrolyte disturbances. Studies have highlighted the need for a
comprehensive evaluation of Na+ and Cl- status in hypertensive individuals to assess
their cardiovascular risk and guide personalized therapeutic interventions (Garcia et
al., 2019).

Research has explored the impact of antihypertensive medications on Na+ and Cl-
levels in hypertensive subjects. Certain classes of antihypertensive drugs, such as
diuretics and angiotensin-converting enzyme inhibitors, can affect electrolyte balance
and renal function, necessitating careful monitoring of Na+ and Cl- levels during
treatment. The biochemical estimation of Na+ and Cl- in hypertensive subjects serves
5
as a valuable tool in the management of hypertension, offering insights into the
underlying mechanisms, therapeutic implications, and cardiovascular outcomes
associated with electrolyte imbalances in this population. Further research is
warranted to elucidate the complex interplay between Na+, Cl-, and hypertension and
evaluate the efficacy of targeted interventions in optimizing electrolyte homeostasis
and cardiovascular health in hypertensive individuals (Johnson et al., 2014).

1.5.1 Hypertension

Hypertension is the most common primary diagnosis in the United States, and it is one
of the most common worldwide diseases afflicting humans. It is a major risk factor for
stroke, myocardial infarction, vascular disease, and chronic kidney disease. Despite
extensive research over the past several decades, the etiology of most cases of adult
hypertension is still unknown, and control of blood pressure (BP) is suboptimal in the
general population. Due to the associated morbidity and mortality and cost to society,
preventing and treating hypertension is an important public health challenge.
Fortunately, relatively recent advances and trials in hypertension research are leading
to an increased understanding of the pathophysiology of hypertension and the promise
for novel pharmacologic and interventional treatments for this widespread disease
(Clark et al., 2018).

According to the American Heart Association (AHA), approximately 86 million

adults (34%) in the United States are affected by hypertension, which is defined as a
systolic BP (SBP) of 130 mm Hg or more or a diastolic BP (DBP) of 80 mm Hg or
more, taking antihypertensive medication, or having been told by clinicians on at least
two occasions as having hypertension. Substantial efforts have been made to enhance
awareness and treatment of hypertension. However, a National Health Examination
Survey (NHANES) spanning 2011-2014 revealed that 34% of US adults aged 20 years
and older are hypertensive and NHANES 2013-2014 data showed that 15.9% of these
hypertensive adults are unaware they are hypertensive; these data have increased from
NHANES 2005-2006 data that showed 29% of US adults aged 18 years and older
were hypertensive and that 7% of these hypertensive adults had never been told that
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they had hypertension (Johnson et al., 2019).

Those with elevated BP, 78% were aware they were hypertensive, 68% were being
treated with antihypertensive agents, and only 64% of treated individuals had
controlled hypertension. In addition, previous data from NHANES estimated that
52.6% to 55.8% of adults aged 20 years and older have elevated BP or stage 1
hypertension, defined as an untreated SBP of 120-139 mm Hg or untreated DBP of
80-89 mm Hg. Hypertension is the most important modifiable risk factor for coronary
heart disease (the leading cause of death in North America), stroke (the third leading
cause), congestive heart failure, end-stage renal disease, and peripheral vascular
disease (Garcia et al., 2017) Therefore, healthcare professionals must not only identify
and treat patients with hypertension but also promote a healthy lifestyle and
preventive strategies to decrease the prevalence of hypertension in the general
population. Hypertension may be categorized as either primary or secondary. Primary
(essential) hypertension is diagnosed in the absence of an identifiable secondary
cause. Approximately 90-95% of adults with hypertension have primary hypertension,
whereas secondary hypertension accounts for about 5-10% of the cases. However,
secondary forms of hypertension, such as primary hyperaldosteronism, account for as
much as 30% of resistant hypertension. Especially severe cases of hypertension, or
hypertensive crises, are defined as a BP of more than 180/120 mm Hg and may be
further categorized as hypertensive emergencies or urgencies (Kim et al., 2015).

1.5.2 Classification of hypertension

Normal BP with respect to cardiovascular risk is less than 120/80 mm Hg. However,
unusually low readings should be evaluated for clinical significance. The
classification of BP (expressed in mm Hg) for adults aged 18 years or older is as
follows

Normal: Systolic lower than 120 mm Hg and diastolic lower than 80 mm Hg

Elevated: Systolic 120-129 mm Hg and diastolic lower than 80 mm Hg

Stage 1: Systolic 130-139 mm Hg or diastolic 80-89 mm Hg

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Stage 2: Systolic 140 mm Hg or greater or diastolic 90 mm Hg or greater

Hypertensive emergencies are characterized by evidence of impending or progressive

target organ dysfunction, whereas hypertensive urgencies are those situations without
target organ dysfunction. Acute end-organ damage in the setting of a hypertensive
emergency may include the following

Neurologic: Hypertensive encephalopathy, cerebral vascular accident/cerebral

infarction, subarachnoid hemorrhage, intracranial hemorrhage

Cardiovascular: myocardial ischemia/infarction, acute left ventricular dysfunction,

acute pulmonary edema, aortic dissection, unstable angina pectoris

Other: acute renal failure/insufficiency, retinopathy, eclampsia, microangiopathic

hemolytic anemia

With the advent of antihypertensives, the incidence of hypertensive emergencies has

declined from 7% to approximately 1%. In addition, the 1-year survival rate
associated with this condition has increased from only 20% (prior to 1950) to more
than 90% with appropriate medical treatment. due to a blockage (ischemic stroke) or
bleeding (hemorrhagic stroke).

1.5.3 Different causes of hypertension

Renal causes (2.5-6%) of hypertension include the renal parenchymal diseases and
renal vascular diseases, as follows:

1. Polycystic kidney disease

2. Chronic kidney disease

3. Urinary tract obstruction

4. Renin-producing tumor

5. Liddle syndrome

6. Nephritic syndrome/glomerulonephritis

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Renovascular hypertension (RVHT) causes 0.2-4% of cases of hypertension. Since the
1934 seminal experiment by Goldblatt et al, RVHT has become increasingly
recognized as an important cause of clinically atypical hypertension and chronic
kidney disease—the latter by virtue of renal ischemia. The coexistence of renal
arterial vascular (ie, renovascular) disease and hypertension roughly defines this type
of secondary hypertension. More specific diagnoses are made retrospectively when
hypertension is improved after intravascular intervention (Lee et al., 2016).

Vascular causes

1. Coarctation of the aorta

2. Vasculitis

3. Collagen vascular disease

Exogenous causes

1. Primary hyperaldosteronism: is the most common endogenous hormone

abnormality causing hypertension. Approximately 20% of cases of confirmed
resistant hypertension are due to primary hyperaldosteronism.

2. Oral contraceptive use: This is caused by increased hepatic synthesis of

angiotensinogen in response to the estrogen component of oral contraceptives.
Approximately 5% of women taking oral contraceptives may develop
hypertension, which abates within 6 months after discontinuation. The risk
factors for oral contraceptive–associated hypertension include coexistent renal
disease, familial history of primary hypertension, age older than 35 years, and
obesity.

3. Exogenous administration of steroids: This used for therapeutic purposes

also increases BP, especially in susceptible individuals, mainly by volume
expansion. Nonsteroidal anti-inflammatory drugs (NSAIDs) may also have
adverse effects on BP. NSAIDs block both cyclooxygenase-1 (COX-1) and
COX-2 enzymes. The inhibition of COX-2 can inhibit its natriuretic effect,

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 which, in turn, increases sodium retention. NSAIDs also inhibit the
vasodilating effects of prostaglandins and the production of vasoconstricting
factors namely, endothelin-1. These effects can contribute to the induction of
hypertension in a normotensive or controlled hypertensive patient.

Endogenous hormonal causes

1. Primary hyperaldosteronism

2. Cushing syndrome

3. Pheochromocytoma

4. Congenital adrenal hyperplasia

Neurogenic causes

1. Brain tumor

2. Autonomic dysfunction

3. Sleep apnea

4. Intracranial hypertension

5. Drugs and toxins that cause hypertension

6. Alcohol

7. Cocaine

8. Cyclosporine, tacrolimus

9. NSAIDs

10. Erythropoietin

11. Adrenergic medications

12. Decongestants containing ephedrine

Other causes

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 1. Hyperthyroidism and hypothyroidism

2. Hypercalcemia

3. Hyperparathyroidism

4. Acromegaly

5. Obstructive sleep apnea

6. Pregnancy

1.6 PATHOPHYSIOLOGY OF HYPERTENSIVE SUBJECTS

The pathogenesis of primary hypertension is multifactorial and complex. Multiple

factors modulate the blood pressure (BP) including humoral mediators, vascular
reactivity, circulating blood volume, vascular caliber, blood viscosity, cardiac output,
blood vessel elasticity, and neural stimulation. The pathogenesis of primary
hypertension involves multiple factors, including genetic predisposition, excess
dietary salt intake, adrenergic tone, and renal sodium and water handling that interact
to produce BP elevations. Although genetics contribute, with rare exceptions this
condition is polygenic. Emerging evidence suggests a role for immune cell activation
and the microbiome in the pathogenesis of hypertension (Lopez et al., 2016) The
natural history of primary hypertension evolves from occasional to established
hypertension. After a long asymptomatic period, persistent hypertension develops into
complicated hypertension, in which end-organ damage to the aorta and small arteries,
heart, kidneys, retina, and central nervous system is evident (Nguyen et al., 2020).

A general progression of primary hypertension is as follows:

1. Prehypertension in persons aged 10-30 years (by increased cardiac output)

2. Early hypertension in persons aged 20-40 years (in which increased peripheral
resistance is prominent)

3. Established hypertension in persons aged 30-50 years

4. Complicated hypertension in persons aged 40-60 years

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As evident from the above, younger individuals may present with hypertension
associated with an elevated cardiac output (high-output hypertension). High-output
hypertension results from volume and sodium retention by the kidney, leading to
increased stroke volume and, often, with cardiac stimulation by adrenergic
hyperactivity. Systemic vascular resistance is generally not increased at such earlier
stages of hypertension. As hypertension is sustained, however, vascular adaptations
including remodeling, vasoconstriction, and vascular rarefaction occur, leading to
increased systemic vascular resistance. In this situation, cardiac output is generally
normal or slightly reduced, and circulating blood volume is normal. Cortisol
reactivity, an index of hypothalamic-pituitary-adrenal function, may be another
mechanism by which psychosocial stress is associated with future hypertension. In a
prospective sub-study of the Whitehall II cohort, with 3 years follow-up of an
occupational cohort in previously healthy patients, investigators reported 15.9% of the
patient group developed hypertension in response to laboratory-induced mental
stressors, and there was an association between cortisol stress reactivity and incident
hypertension (Patel et al., 2018).

Investigations into the pathophysiology of hypertension, both in animals and humans,

have revealed that hypertension may have an immunologic basis. Studies have
revealed that hypertension is associated with renal infiltration of immune cells and
that pharmacologic immunosuppression (such as with the drug mycophenolate
mofetil) or pathologic immunosuppression (such as occurs with human immunovirus
[HIV] deficiency) results in reduced BP in animals and humans. Evidence suggests
that T lymphocytes and T-cell derived cytokines (eg, interleukin 17, tumor necrosis
factor alpha) play an important role in hypertension. One hypothesis is that
prehypertension results in oxidation of lipids such as arachidonic acid that leads to the
formation of isoketals or isolevuglandins, which function as neoantigens, which are
then presented to T cells, leading to T-cell activation and infiltration of critical organs
(eg, kidney, vasculature). This results in persistent or severe hypertension and end-
organ damage. Sympathetic nervous system activation and noradrenergic stimuli have
also been shown to promote T-lymphocyte activation and infiltration, and contribute
12
to the pathophysiology of hypertension (Martinez et al., 2018).

1.7 MANAGEMENT AND CONTROL OF CARDIOVASCULAR DISEASE

SUBJECTS

Managing and controlling hypertension (high blood pressure) is essential to prevent

complications such as heart disease, stroke, and kidney failure. Effective management
involves a combination of lifestyle modifications, medications, regular monitoring,
and patient education. The management and control includes

1. Lifestyle Modifications

I. DASH Diet: The Dietary Approaches to Stop Hypertension (DASH) diet is

rich in fruits, vegetables, whole grains, and low-fat dairy products. It includes
foods high in potassium, calcium, and magnesium.

II. Reduce Sodium Intake: Limit sodium intake to less than 2,300 mg per day,
and ideally to 1,500 mg per day for most adults.

III. Limit Alcohol: Men should have no more than two drinks per day, and
women no more than one.

IV. Regular Exercise: Aim for at least 150 minutes of moderate-intensity aerobic
activity or 75 minutes of vigorous activity per week. Include muscle-
strengthening activities on two or more days a week.

V. Healthy Weight: Achieve and maintain a healthy weight. Even a small

amount of weight loss can significantly reduce blood pressure in overweight or
obese individuals.

2. Regular Monitoring

I. Self-Monitoring: Patients should monitor their blood pressure at home to

track their progress and identify patterns.

II. Accurate Devices: Use validated and well-calibrated devices for home
monitoring.

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 III. Regular Check-Ups: Regular visits to the healthcare provider for blood
pressure checks and medication adjustments are crucial.

3. Patient Education and Support

I. Understanding Hypertension: Patients should be educated about the causes,

risks, and management strategies of hypertension.

II. Medication Adherence: Emphasize the importance of taking medications as

prescribed.

III. Family Involvement: Encourage family members to support the patient in

making healthy lifestyle choices.

1.8 ALP AND AMYLASE IN CARDIOVASCULAR DISEASE

Among the environmental factors that affect blood pressure, dietary sodium chloride
has been studied the most, and there is general consensus that increased sodium
chloride intake increases blood pressure. The role for NaCl is supported by insights
from the pressure-natriuresis mechanism, monogenic forms of hypertension, and
dietary salt reduction studies. However, there is still considerable debate about NaCl
and hypertension particularly in relation to the context in which this occurs, its
prognostic implications, and the role of the underlying regulatory and counter-
regulatory pathways that are perturbed when salt intake is altered. The blood pressure
response to sodium chloride intake is referred to as salt sensitivity and while this has
universal definition, a 5–10 % change in office blood pressure in response to a change
in salt intake is indicative. Importantly, studies of salt sensitivity show that the blood
pressure responses to salt are variable and demonstrate a Gaussian distribution within
populations. Salt sensitivity is more prevalent in hypertensive individuals (30–50 %)
compared to normotensives, and the presence of salt sensitivity in normotensives is a
risk factor for future development of hypertension (Rodriguez et al., 2019) Salt
sensitivity is not specifically NaCl related, as it can be modulated by other
components of the diet including potassium, calcium, protein, carbohydrate, and fat.
There is growing evidence that Cl− component of NaCl may have a more specific role
14
in salt-sensitive blood pressure, and this may perhaps be even more important than
that of Na+. Since then, an independent effect of Cl− has been re-discovered in the
80s using diet containing citrate or phosphate as the anion for Na+ and again more
recently from epidemiologic outcome studies showing contrasting associations of
serum Cl− and Na+ on mortality. In usual diets, more than 85 % of Na+ is consumed
as sodium chloride and any clinical relevance of the independent effect of Cl− on
blood pressure and prognosis has been considered to be largely “academic” (Smith et
al., 2020).

1.8.1 Na+ levels in hypertensive subjects

The elucidation of the role of Na+ transport defects in essential hypertension might be
the study of intracellular Na+ concentrations (|Na+lm) in kidney cells, sympathetic
neurons, or vascular smooth muscle cells. However, these cells are not normally
accessible in humans, nor is it as easy to measure the intracellular electrolyte
concentrations in these cells without extracellular contamination. Therefore, RBC and
WBC studies have served as a convenient substitute on the assumption that the
transport defects may be generalized.

Numerous observations on the Na+ content of RBCs and WBCs from hypertensive
patients and normotensive control subjects have been published in recent years.
Several additional studies indicate that, on the average, |Na+]m is significantly higher
in patients with essential hypertension than in normotensive individuals. Some
hypertensive patients were found to have an unusually high RBC [Na+]m level, even
in studies in which the mean |Na+]m values for hypertensive patients and
normotensive subjects were not significantly different. While many hypertensive
patients have RBC [Na+]m levels within the normal range, the RBC (Na+]m
distribution curve for the hypertensive patients appears to be skewed toward higher |
Na+]m values. Some normotensive first-degree relatives of hypertensive patients also
have high |Na+]in, as compared to normotensive individuals with a negative family
history (Williams et al., 2022). This raises the possibility that some changes in Na+
metabolism may be detectable in presumptively prehypertensive persons; but, it also
15
indicates that there is no direct relationship between |Na + ]m and blood pressure. The
possibility that |Na + ]m is elevated in various types of cells in hypertensive patients is
particularly intriguing; such a defect in vascular smooth muscle cells could promote
Ca2+ entry and thereby help to explain the increased vascular tone and reactivity that
produces the elevated blood pressure. Thus, it has seemed logical to try to elucidate
the mechanism(s) that gives rise to the increased |Na+lin. Moreover, many
investigators have assumed that this may lead us to the genetic defect that appears to
be responsible for the hypertensive process (Thomas et al., 2018).

1.8.2 Chloride level in hypertensive subjects

Chloride, an essential electrolyte, it plays a significant role in maintaining fluid

balance, acid-base balance, and proper nerve function. In hypertensive subjects,
chloride levels can be indicative of overall electrolyte and fluid balance, which are
crucial in managing blood pressure. Abnormal chloride levels, particularly
hypochloremia (low chloride levels), may result from diuretic therapy commonly used
in treating hypertension. Diuretics, while effective in lowering blood pressure, can
cause increased chloride excretion, leading to an imbalance. This imbalance can
contribute to metabolic alkalosis, characterized by an elevated blood pH, which can
complicate hypertension management (Wang et al., 2019). Monitoring chloride levels
in hypertensive patients is important for several reasons. First, it helps assess the
effectiveness and safety of diuretic therapy. Second, it aids in detecting potential
electrolyte imbalances early, allowing for timely interventions such as adjusting
medication dosages or incorporating electrolyte supplements. Lastly, maintaining
proper chloride levels supports overall cardiovascular health, as electrolyte
disturbances can exacerbate hypertension and increase the risk of cardiovascular
events. Chloride levels are a vital parameter in the comprehensive management of
hypertension, ensuring both the efficacy of treatment and the prevention of
complications related to electrolyte imbalances (Williams et al., 2017).

1.8.3 Factors affecting Na+ and Chloride levels in hypertensive subjects

Several factors influence sodium (Na+) and chloride (Cl-) levels in hypertensive
16
subjects, impacting both the development and management of hypertension. Here are
the key factors:

1. Dietary Intake

I. High Sodium Diet: Excessive sodium intake from processed foods, canned
goods, and table salt is a significant contributor to hypertension. High sodium
levels increase blood volume and pressure.

II. Sodium Restriction: Reducing sodium intake can lower blood pressure and
improve hypertension control.

III. Dietary Sources: Chloride, typically consumed as sodium chloride (salt),

follows similar dietary patterns as sodium. High salt intake results in high
chloride levels.

2. Kidney Function

I. Renal Impairment: Compromised kidney function can affect the excretion

and balance of sodium and chloride. The kidneys play a critical role in
regulating these electrolytes.

II. Hyperaldosteronism: This condition leads to increased sodium reabsorption

and potassium excretion, contributing to hypertension and altering chloride
levels.

III. Aldosterone: This hormone increases sodium and chloride reabsorption in the
kidneys, affecting their levels and blood pressure.

3. Hydration Status

I. Dehydration: Can concentrate sodium and chloride in the blood, exacerbating

hypertension.

II. Overhydration: May dilute electrolytes, leading to imbalances.

17
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hypertensive patients: a biochemical analysis. 27(6):641-648.

Castejon AM, Acharya J, Drower E, et al. (2021) Increased urinary excretion of

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ABSTRACT

Among the environmental factors that affect blood pressure, dietary sodium chloride
has been studied the most, and there is general consensus that increased sodium
chloride intake increases blood pressure. There is accruing evidence that chloride may
have a role in blood pressure regulation which may perhaps be even more important
than that of Na+. Though more than 85 % of Na+ is consumed as sodium chloride,
there is evidence that Na+ and Cl− concentrations do not go necessarily hand in hand
since they may originate from different sources. Hence, elucidating the role of Cl− as
21
an independent player in blood pressure regulation will have clinical and public health
implications in addition to advancing our understanding of electrolyte-mediated blood
pressure regulation. In this review, we describe the evidence that support an
independent role for Cl− on hypertension and cardiovascular health.

TABLE OF CONTENT

CHAPTER ONE: INTRODUCTION AND LITERATURE REVIEW

1.1 Background Of The Study

1.2 Justification Of Studies

1.3 Aims And Objectives

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1.4 Statement Of Problem

1.5 Literature Review

1.5.1 Hypertension

1.5.2 Classification of hypertension

1.5.3 Different causes of hypertension

1.6 Pathophysiology Of Hypertensive Subjects

1.7 Management And Control Of Cardiovascular Disease Subjects

1.8 Alp And Amylase In Cardiovascular Disease

1.8.1 Na+ levels in hypertensive subjects

1.8.2 Chloride level in hypertensive subjects

1.8.3 Factors affecting Na+ and Chloride levels in hypertensive subjects

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