Kidney Diseases and Elevated Levels of Blood Urea, Uric Acid and Creatinine

There could be minimal to gross impairment of renal function during the onset and progression of a kidney disease or renal disorder. This impairment of renal function may range from subclinical to complete renal failure. Urine analysis and blood biochemistry have been of great help in the assessment of renal function. Simultaneous increase in the levels of blood urea and uric acid has been observed during a variety of renal disorders. Uric acid is an end product of purine (a component of nucleic acids and nucleoproteins) metabolism. The level of uric acid in the blood depends on its endogenous production through purine metabolism as well as from the exogenously taken purines in the food items. Normal range of uric acid in blood is 2 - 6mg/dl. Elevated level of uric acid is also observed in gout. Urea is an end product of protein metabolism and its normal range in blood is 20 - 40mg/dl.

Formation of Urea: The amino acids derived by the digestion of proteins of the food we eat are absorbed by the villi of the small intestine and brought to the liver through the portal vein. The essential amino acids required for the growth and repair of body tissues are passed on to the blood circulation by the liver and others are used to produce the blood proteins and useful proteins for the body. Useless proteins are broken down in the liver to form bioenergy composed of carbon, hydrogen and oxygen and a waste product urea. Urea is a water soluble substance and carried away buy the blood stream.

The uric acid level may increase earlier than the blood urea level during the course of renal disease. The serum uric acid could be found markedly increased from the normal level of 2 -6mg/dl to 10 - 30mg/dl with minimal impairment of renal function. The creatinine level in blood starts rising after 2 to 4 fold rise in the blood urea level. The level of urea may rise in a variety of conditions, but increased level of creatinine is considered more severe than the increased level of blood urea. The creatinine is derived from the creatine and is a waste product; on the other hand the creatine is necessary for the muscle contraction and is related to the phosphocreatine breakdown. The normal level of creatinine in the blood plasma or serum is 1 - 2mg/dl and its normal daily excretion ranges from 1 to 2 grams. The serum creatinine values of up to and even exceeding occasionally 20mg/dl have been seen in the later stages of renal failure. The major cause of increased levels of serum creatinine and blood urea is the poor clearance of these substances by the kidneys rather than excessive production. In acute glomerulonephritis values from normal to over 300mg/dl are generally observed. In conditions such as malignant hypertension, chronic pyelonephritis and heavy metal poisoning 10 to 15 fold increase in blood urea level may be detected. However, in cases of hypoadrenalism (Addison's disease) blood urea level of about 100mg/dl could be detected. Fifteen to 20 fold increase in the level of blood urea (i.e. a level of 600 - 800mg/dl) may lead to uremic coma in more than 80% cases of cases affected by severe renal disease or renal failure.

Role of Adrenal Glands in Renal Physiology

The role of adrenal glands in the control of functioning of kidneys is very well established in terms of renal physiology. Every organ of our body has an embryonal origin and relationship with other organs. This relationship helps us to establish the physiology of systems associated with each other. There exists a pair of adrenal glands in our body and their position is suprarenal. Each adrenal gland has a cortex and medulla. There exists three layers of specialized cells in the adrenal cortex and these are: (1) Zona glomerulosa, (2) Zona fasciculata and (3) Zona reticularis. The medullae of adrenal glands belong to chromaffin system. The pituitary adrenocorticotrophic hormone (ACTH) controls the activity of adrenal glands in the production of cortisol (hydrocortisone). The inner medullary portion of the adrenal glands produces adrenaline (epinephrine) and noradrenaline (norepinephrine). The adrenal glands function under the control of sympathetic nervous system. The production of adrenal hormones increases in the conditions of emotions like anger or fear and states of asphyxia (lack of oxygen) and starvation and in turn raises the blood pressure in order to overcome the shock. The adrenaline epinephrine) influences the flow of urine and helps in the water balance by kidneys. Noradrenaline norepinephrine) is known to stimulate the muscle fibres in the walls of blood vessels, causing them to contract and thus raising the blood pressure. Adrenaline (epinephrine) also accelerates the carbohydrate metabolism by increasing the output of glucose from the liver.

The cortical layers of adrenal glands produce three types of steroids: (1) Mineralocorticoids are produced by the zona glomerulosa layer of the adrenal cortex and are associated with renal control of water and electrolytes. The mineralocorticoid naturally produced by the adrenal glands is aldosterone which controls the reabsorption of salts by the renal tubules. When there is deficiency of this hormone, too much water and sodium are lost from the body in the urine and too little potassium is excreted and this may lead to toxic levels of potassium in the blood. This results in polyuria, the passage of an excessive quantity of urine. The first of the adrenal steroids isolated or synthesized was the mineralocorticoid called desoxycorticosterone (DOC), which is used in the treatment of shock and polyuria, (2) Glucocorticoids are produced by the middle layer or zona fasciculata of the adrenal cortex and are associated with the metabolism of carbohydrates, fats and proteins. Glucocorticoids promote the conversion of proteins into glucose and storage of glucose as glycogen in the liver. Mineralocorticoids and glucocorticoids complement the action of each other and (3) Androsterone or androgens (sex hormones) are produced by the innermost layer or zona reticularis of the adrenal cortex. Androgens possess 19 carbon atoms in their chemical structure, with one oxygen atom attached to the 17^th carbon atom and are also known as 17-ketosteroids and could normally be detected in the urine. Corticoids are chemically similar to cholesterol, sex hormones or corticosteroids. Our kidneys regulate the volume and composition of our body fluids in terms of water and electrolytes' balance through filtration, secretion, reabsorption and excretion. It is well established that kidneys function under the intelligent control of hormones, without which it would not be possible for the kidneys to maintain a state of homoeostasis in the body.