Urinary System

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Chapter: Medicinal Chemistry : Urinary System

The kidneys do the major work of urinary system. The structural and functional units of kidneys are nephron.


Urinary System

INTRODUCTION

The kidneys do the major work of urinary system. The structural and functional units of kidneys are nephron. The clinical importance of urinary system includes hypertension, heart failure, renal failure, nephritic syndrome, and cirrhosis. The haemodynamics of renal system has a capability to alter the aforesaid pathological conditions.


Functions of Renal System

The functions of renal system are as follows:

Regulation of blood ionic compounds: The kidneys help to regulate the blood ions, i.e., sodium (Na+), potassium (K+), calcium (Ca2+), chloride (Cl) and phosphate ions (HPO42–)

Regulation of blood pH: The kidneys excrete a variable amount of hydrogen ions (H+) into the urine and conserve bicarbonate (HCO3) ions, which regulate pH of blood.

Regulation of fluid volume: The kidneys adjust blood volume by eliminating water in urine.

Regulation of blood pressure (BP): BP is regulated by the kidneys through an enzyme called renin secreted by ju xtra glomerular cells, which activates the renin-angiotensin-aldosterone (RAA) pathway. Increased renin causes increase in BP.

Maintenance of blood osmolarity: The kidneys produce two hormones, calcitrol and erythropoietin. Calcitrol, the active form of vitamin D helps to regulate calcitrol homeostasis and erythropoietin stimulates the production of red blood cells (RBCs).

Regulation of blood glucose level: The kidneys can use the amino acid of glutamine in gluconeogenesis and release blood to maintain sugar level.

Excretion of metabolite waste products and foreign substances: Metabolic products like ammonia, urea, bilurubin, creatinine, uric acid, and other substances, i.e., toxins of exogenous compounds and drug metabolites, etc., are excreted through urine.

Renal haemodynamics is altered by diuretics in clinical medicine. The therapeutic applications of diuretics are mainly concerned with hypertension and heart failure.

The normal renal physiological process includes glomerular filtration and tubular reabsorption.


PRINCIPLE OF GLOMERULAR FILTRATION

In glomerular capillaries, a portion of plasma water is formed through a filter, which functions due to the fenestrated capillary epithelial cells and the filtration diaphram formed by epithelial cells; solutes of small size flow with filtered water into the urinary space whereas formed elements and macromolecules are retained by the filtration barrier. The glomerular filtration depends on the hydrostatic pressure in Bowman’s capsule space. Glomerular filtration rate (GFR) averages 125 ml/min in males and 105 ml/min in females. The mechanism regulates GFR in two ways—(i) by adjusting blood flow into and out of glomerulus and (ii) by altering glomerular capillary surface area available for filtration.


PRINCIPLE OF TUBULAR REABSORPTION AND SECRETION

The volume of fluid entering the proximal convoluted tubules in half an hour is more than the total blood plasma volume—normally about 99% of filtered water is reabsorbed. Solutes that are reabsorbed by both active and passive process include glucose, amino acids, urea, and ions, i.e., Na+, K+, Ca2+, Cl, HCO3 (bicarbonates), and HPO42– (phosphates). Once the fluid passes through the proximal convoluted tubule, the cells that are located more distally, tune the reabsorption processes to maintain homeostatic balance of water and selected ions. Most of the small proteins and peptides that pass through the filter is also reabsorbed by pinocytosis. In tubular secretion, the transfer materials from the blood and tubule cells enter into tubular fluid includes hydrogen ions (H+), potassium (K+), ammonium (NH4+), creatinine, and certain drugs like penicillin. The general membrane transports are Na+-ATPase pump, in basolateral membrane, which hydrolyzes ATP resulting in transport of Na+ into intracellular and interstitial spaces. Na+ may diffuse across the luminal membrane through sodium channels into epithelial cell down through the electrochemical gradient, which is established by basolateral Na+-K+-ATPases. In addition, free enzyme available in electrochemical gradient for Na+ is trapped by integral protein of luminal membrane resulting in co-transporters of various solutes against their electrochemical gradient by symports (e.g. Na+-glucose, Na+-H2 PO4, and Na+-amino acid). Na+ exits basolateral membrane into intercellular and interstitial spaces through Na+ pump; their accumulation creates small osmotic pressure difference across the epithelial cell.

In water-permeable epithelium, water moves into the intracellular spaces driven by osmotic pressure difference. Movement of water into intracellular space concentrates other solutes in the tubular fluid, resulting in an electrochemical gradient for these substances across the epithelium. Membrane permeable solutes then move down their electrochemical gradients into the intracellular spaces through both transcellular (e.g. simple diffusion, symporters, antiporters, uniporters, and channels) and paracellular pathways. Membrane impermeable solutes that remain in the tubular lumen are excreted in the urine with an obligatory amount of water. As water and solutes accumulate in intracellular space the hydrostatic pressure increases, providing a driving force for bulk water flow.

There are other mechanisms that secrete organic acid and organic base secretions. Nine different organic acids and five different organic base transporters exists. Other regulations include cation and anion by Ca2+-ATPase, Na+-Pi (sodium inorganic phosphate) symport, Na+-Mg+ antiport, and Mg2+ ATPase.

The rate of urinary excretion can be expressed by the following equation:

Urinary output = Glomerular filtration + Tubular secretion –Tubular reabsorption


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