Biochemical Aids to Clinical Diagnosis

PREM PRAKASH KUSHWAHA,1 P. SESHU VARDHAN,2 K. VISHNUPRIYA,3 SHARMISTHA SINGH,4 and SHASHANK KUMAR1

School of Basic and Applied Sciences, Department of Biochemistry, Central University of Punjab, Bathinda, Punjab-151001, India,

Tel.: +91 9335647413,

E-mail: This email address is being protected from spam bots, you need Javascript enabled to view it (S. Kumar)

  • 2School of Biotechnology, jawaharlal Nehru Technological University, Kakinada-500085, Telangana, India
  • 3 Protein Bioinformatics Lab, Department of Biotechnology,

Indian Institute of Technology, Madras - 600036, Tamil Nadu, India 4Department of Biochemistry, University of Allahabad, Allahabad, India

ABSTRACT

Microorganism is typically responsible for the several human diseases. This disease can be identified by various assays using different biological sample. Numerous enzymes and their levels present in the different biological sample reveals the condition of the patients. Substances present in the serum such as urea and creatinine explores the condition of the kidney health. Enzymes, ions, and hormones like alkaline phosphatase (ALP), lactate dehydrogenase (LD), neuron-specific enolase, cathepsins, calcitonin, calcium, phosphorus, blood urea nitrogen (BUN) and electrolytes demonstrates several organs function and their health.

INTRODUCTION: CARDIOVASCULAR DISEASES (CV)

Cardiovascular disease (CV) is the major cause of enervation as well as hasty death worldwide. Atherosclerosis is an underlined pathology of CV;

require an extensive time to grow. One can have its symptoms generally in middle age. In CV, sudden and frequent occurrence of acute coronary proceedings occurs and is often fatal. CV might diagnose by different laboratory tests and imaging techniques. Some of the common tests for CV diagnosis are as follows:

  • • Tests for heart disease risk factors include cholesterol, lipid (LDL, HDL, Triglycerides) and fats levels in the blood.
  • • Glycosylated Hb in blood is used to diagnose diabetes. For inflammation (that might lead to heart disease), different protein tests such as C-reactive protein (CRP) test, and apolipoprotein Al/B are used.
  • • During heart attack, myocardial cells release some protein and factors into the bloodstream. These factors are important signature of a recent heart attack. Cardiac Troponin-T, increased homocysteine level and asymmetric dimethylarginine, brain natriuretic peptide (BNP), fibrinogen, and PAI-1, are some important marker of heart attack.

FUNCTION AND DISEASES RELATED TO KIDNEY

In our body evacuation of water-soluble waste products is the key role of kidney. Besides filtration and secretion is also the major responsibility of kidney. Deregulation of these functions results in the decreased excretion and accumulation of waste products in the body. Assessment of various proteins and molecules in urine might be used for kidney function:

  • • Urine examination;
  • • Urea clearance;
  • • Serum urea;
  • • Serum electrolyte levels;
  • • Serum creatinine;
  • • Blood urea nitrogen (BUN);
  • • Calcium;
  • • Concentration-dilution test;
  • • Protein;
  • • Albumin;
  • • Creatinine clearance;
  • • Phosphorus;
  • • Inulin clearance.

URINE EXAMINATION

A qualitative examination of urine provides an idea about nature and site of damage in the renal system. Color, odor, quantity, specific gravity of the urine is some parameter for qualitative assessment of urine. Pus cells, RBC casts, and crystals are some microscopic inspection of the urine sample.

SERUM UREA

Amino acid metabolism and protein catabolism pathways are related to the production of urea in the body. Urea production occurs in the liver by urea cycle which later on undergoes filtration in glomerulus secretion and tubular level re-absorption. Enhancement in serum urea levels indicates renal/ glomerular dysfunction. The normal concentration of serum urea is 20-45 mg/dl and is affected by diet and some non-kidney associated ailment also.

BLOOD UREA NITROGEN (BUN)

BUN generally expressed in terms of serum urea. Urea is a 60 mw molecule has two nitrogen atoms and has collective atomic weight of 28. Thus, in serum, nitrogen contribution to the total weight of urea is 28/60 and corresponds to 0.47. Serum urea level can be simply transformed into a BUN by multiplying it level by 0.47.

CALCIUM

Calcium test for the renal disturbance measures Ca in blood only, not in our bones. This test gives an idea about parathyroid glands, kidney, cancer, and bone problems. The standard range of Ca2+ in blood is 8.5 to 10.2 mg/dl.

PHOSPHORUS

Phosphorus is an important constituent of bones and teeth, support nerve function and muscle contraction. Extra quantity of phosphate in the blood is decanted by the kidneys and flow away in the urine. Elevated levels of phosphorus have been in the patients of severe kidney disease.

PROTEIN

Protein level estimation in urine is a very sensitive and wide-range screening test for renal ailment. It is strikingly augmented in renal disease. The highest degree of proteinuria was found in nephrotic syndrome (>3-4 g/day). The renal disease having nephrotic syndrome, urinaiy protein flow rate is typically about 1-2 g/day.

SERUM CREATININE

Creatine (Cr) is a trivial tripeptide mostly occurs in muscles and is nontoxic. It liberates from the muscles and gets converted into Cr. Cr is not a noxious product and is applied as a symbol of renal function. Normal serum Cr level is 0.6-1.5 mg/dl. It is a preferable pointer of renal and glomerular function. Cr is mostly calorimetrically measured by Jaffe's method in clinical laboratories.

UREA CLEARANCE

Urea clearance stands for the excretion of blood urea with the help of kidney within one minute. Urea clearance measured by urea level in the blood, urine, and quantity of urine expelled over a break of one hour.

CREATININE CLEARANCE RATE

Creatinine filtration at glomerulus and reabsorption at tubular level is irrelevant. Due to this creatinine, clearance may be used to quantify glomerular filtration rate (GFR).

INULIN CLEARANCE

Inulin is a trivial polysaccharide made up of fructose and is a veiy low molecular weight compound. It is utilized for the measurement of GFR.

GFR is the quantity of blood that passes and sieved through glomerulus per minute.

CONCENTRATION TEST

Kidney has ability to concentrate lodged water and urine by increasing its reabsorption from the glomerular filtrate at the tubular level. This function of kidney is a measure of tubular function. The conspicuous gravity of as minimum as one sample should be 1.025 or above, in a normal person. Specific gravity below the 1.025 is an indication of tubular dysfunction.

ELECTROLYTES

Kidney balances the water content and its excretion which leads into the maintenance of electrolyte balance in the body. It actively reabsorb/excrete electrolytes and thereby maintains the electrolyte balance.

Filtration and reabsoiption of electrolytes occurred at the glomerulus and tubular level respectively. Problem at tubular level results in non-absorptive and excessive loss of electrolytes in the urine. Important serum electrolytes to explore the tubular level problem are sodium (135-145 mmol/liter), potassium (3.5-5 mmol/liter), and chloride ions (95-105 mmol/liter).

LIVER DISEASE

The adult liver weighs approximately 1.2-1.5 kg, positioned underneath the diaphragm in the right upper part of abdomen, protected by the ribs. It carries out a number of excretory, synthetic, and metabolic functions. Endogenous and exogenous organic anions are removed from sinusoidal blood, bio-transformed, and expelled into the bile or urine. Excretory function evaluation delivers appreciated clinical information. Measurement of plasma concentrations of endogenous products such as bilirubin and bile acids, and the assessment of clearance rate of exogenous products (aminopyrine, lidocaine, and caffeine) are the most recurrently used examinations for the diagnosis of liver delinquent. A number of circumstances are symptomatic of liver problem such as jaundice, portal hypertension, obnoxious hemostasis, and enzyme secretion into body fluids. Jaundice is characterized by the appearance of mucous membrane, yellowish skin, and bilirubin deposition (sclera).

Jaundice is frequently ostensible when plasma bilirubin concentration reaches up to 34 to 51 pmol/L (2-3 mg/dL). Ascites is the outpouring and gathering of fluid inside the abdominal cavity. It is uncomfortable and compromise respiration but not a life-threatening state. Portal hypertension is an increase in the difference between plasma and ascitic fluid albumin concentration. A gradient >1.1 g/dL is symptomatic of ascites triggered by portal hypertension. Ascites predisposes to spontaneous bacterial peritonitis is defined as bacteremia (i.e., presence of bacteria in the blood) in the absence of power-driven disruption of bowel. The diagnosis can be achieved by ascitic fluid examination; >250 neutrophils per microliter, or >500 in the death of a positive blood culture, is considered as positive diagnostic. Sometimes patients having liver disease showed normal hepatic function tests. In liver disease increased levels of plasma, activity of many cytosolic, mitochondrial, as well as membrane- associated enzymes has been reported.

Several factors administrate the potential of liver enzymes capability to support diagnosis, including their tissue specificity, subcellular distribution, comparative degree of enzyme commotion in liver and plasma, pattern of release, and clearance from the plasma. Although jaundice is a crucial clinical event tending leading to recognition of acute hepatitis, is often absent. AST activity more than 200 IU/L, or ALT activity more than 300 IU/L, has clinical specificity and sensitivity of more than 90% for acute hepatitis (Burtis and Bruns. 2014).

THYROID DISORDER

Thyroid gland has butterfly-like appearance, situated in the opposite of neck impartial upstahs the trachea in mature human being. Thyroid gland of a mature human weighs about 15-20 g and comprise two lobes linked by isthmus. Thyroid follicles are the secretory unit of thyroid gland. Epithelial cells form an exterior layer on individual follicle encompassing an amorphous material called colloid. Colloid is principally composed of thyroglobulin (Tg) has trivial extents of iodinated thyroid-albumin. The thyroid gland similarly has additional type of cell known as parafollicular or C cells. These cells produce the polypeptide hormone called calcitonin. These cells are restricted within the follicular basement lamina or occur in clusters in the inter-follicular area. The two hormones secreted by thyroid gland (thyroxine and triiodothyronine) are commonly known as T4 and T3 respectively. Thyroid hormones have much important biological effect. A major function of these hormones is to regulate BMR and calorigenesis via augmented oxygen feasting in tissue through the possessions of thyroid hormone on membrane transportation (cycling of Nai/K+-adenosine triphosphatase (ATPase) with increased synthesis and consumption of adenosine triphosphate) and enhanced mitochondrial metabolism (stimulation of mitochondrial respiration and also oxidative phosphorylation). Almost all laboratory tests for thyroid function are commercially available in kit form for on automated immunoassay instruments. High sensitivity assays for TSH are available for various signal detection such as chemiluminescence and assays with low end detection limits in the range of 0.01 to 0.05 mlU/L. Secretion of TSH occurs in a circadian fashion: highest concentrations prevail at night (between 200-400) and lowest concentrations occur in the range of 1700-1800. Low amplitude oscillations also occur throughout the day. Increase in TSH in vespertine is lost in critical illness and after surgeiy. TSH flows immediately after birth, peaking at 30 minutes at 25 to 160 mlU/L; then values drop down to cord blood concentration in three days and reach at adult values in the first weeks of life. Immunoassays of total T4 measures both free and protein-bound thyroxine. Accurate measurement of total endogenous hormone therefore requires alienation of T4 horn its serum transport proteins because 99.97% of the T4 circulates tightly bound to albumin, TBG, and TBPA. Hypothyroidism and hyperthyroidism are the two principal pathological circumstances related to thyroid gland. Patients with hyperthyroidism characteristically have serum TSH concentrations <0.05 mlU/L (Burtis and Bruns, 2014).

 
Source
< Prev   CONTENTS   Source   Next >