MECHANISM OF URINE FORMATION

Mechanism of urine formation (Normal human physiologic process related to clinical chemistry)

Definitions

·         Nephron is the functional unit of the kidney

·         Filtration is the passage through filter or other materials that prevent passage of certain molecule particle, or substance.

·         Glomerular filtration is a movement of plasma filtrate across the three cellular layers (the capillary wall membrane, the basement membrane, and visceral epithelium) into the  Bowman’s capsule as results of pressure difference.

·         Tubular Reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood.

·         Tubular Secretion is the transfer of material from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport.

• Urine excretion is also known as micturition, voiding, peeing, and more rarely, emiction, is the process of disposing of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urine excretion is under voluntary control.

Other Definitions:

·         Osmorality is the concentration of solution in terms of osmoles of solute per liter of solution.

·         Renal threshold, is the amount of a substance in plasma above which appears/excreted in urine.

Introduction to production of urine

·         Nephrons are the functional units of the kidney because they are the smallest structural components capable of producing urine. The function of nephron reflect the process involved in urine production

Urine is formed in three steps:

·         Filtration

·         Reabsorption

·         Secretion

 Glomerular Filtration Process 

·         Glomerular filtration is a movement of plasma filtrate across the three cellular layers (the capillary wall membrane, the basement membrane, and visceral epithelium) into the  Bowman’s capsule as results of pressure difference.

·         The amount of filtrate produced each minute is called the glomerular filtration rate (GFR) is 125mls/minutes.  Creatinine can be measured in serum and urine to estimate glomerular filtration rate (creatinine clearance test).

·         Normally, GFR is about 180 L/day but much of the volume is reabosrbed, leaving 1.5 L/day of fluid to be excreted in the urine.

·         The formation of filtrate depend on a pressure gradient, called the filtration pressure, which forces fluid from the glomerular capillary across the filtration membrane into the lumen of Bowman’s capsule.

·         Only small molecular weight substances can be filtered out from the plasma.  Blood cells, proteins and protein-lipid complexes or other large molecules should not appear in the filtrate and only appear in urine due to diseases or disorders.

·         Refer to the figure for the glomerulus and tubules within the nephron.

http://www.nlm.nih.gov

Tubular Reabsorption 

·         Selective reabsorption takes place in the proximal convoluted tubule of the kidney. It is the process by which certain small molecular weight substances that are required by the body (such as glucose, amino acids, vitamins and water) that have been filtered out of the blood during ultrafiltration, are reabsorbed to the peritubular capillaries. These are capillaries that surround the tubules and provide blood back to circulation for the rest of the body. As only certain substances are reabsorbed, it is known as selective reabsorption.

·         In this way, many useful solutes (primarily glucose and amino acids), salts and water that have passed in the proximal tubule through the Bowman's capsule, return in the circulation by active transport and other methods.

·         Over half of the filtered sodium and water and a slightly lower percentage of filtered chloride are reabsorbed by the proximal tubule before the filtrate reaches the loops of Henle

·         The loop of Henle is highly permeable to water and moderately permeable to most solutes, including urea and sodium. About 20 per cent of the filtered water is reabsorbed in the loop of  Henle

·         Because it is essential to maintain a precise balance between tubular reabsorption and glomerular filtration, there are multiple nervous, hormonal, and local control mechanisms that regulate tubular reabsorption, just as there are for control of glomerular filtration.

 Tubular Secretion 

·         As the glomerular filtrate enters the renal tubules, it flows sequentially through the successive parts of the tubule-the proximal tubule, the loop of Henle, the distal tubule, the collecting tubule, and, finally, the collecting duct-before it is excreted as urine.

·         Along this course, some substances are selectively reabsorbed from the tubules back into the blood, whereas others are secreted from the blood into the tubular lumen.

·         Eventually, the urine that is formed and all the substances in the urine represent the sum of three basic renal processes-glomerular filtration, tubular reabsorption, and tubular secretion-as follows:

·         Some substances are removed from blood through the peritubular capillary network into the distal convoluted tubule or collecting duct, by secretion mechanism.

·         These substances are Hydrogen ions, creatinine (when it is in extreme excess in the blood), and drugs.

·         Substances which are not reabsorbed after glomerular filtration and those secreted into the tubules forms the components of Urine

·         Urine contains much more urea, uric acid and creatinine than serum or plasma due to kidney function.

·         For many substances, reabsorption plays a much more important role than does secretion in determining the final urinary excretion rate. Reabsorption is important in maintaining water, electrolyte and nutrient balance.

·         However, secretion accounts for significant amounts of potassium ions, hydrogen ions, and a few other substances that appear in the urine.  Secretion is important in regulating blood pH and makes urine pH, generally more acidic.

·         For a substance to be reabsorbed, it must first be transported across the tubular epithelial membranes into the renal interstitial fluid and then through the peritubular capillary membrane back into the blood

Composition of Urine

·         Is clear and amber in colour due to the presence of urobilin

·         The specific gravity is between 1020 and 1030, and the pH is around 6(normal range of 4.5 to 8)

·         The healthy adult passes 1000-1500mls per day

·         Composition;

o   Water 96%, urea 2% and others like Ammonia, Potassium ,Sodium etc 2%

 Urine excretion (Mechanism of Micturition) 

·         Urination, also known as micturition, voiding, peeing, and more rarely, emiction, is the process of disposing of urine from the urinary bladder through the urethra to the outside of the body. In healthy humans the process of urination is under voluntary control.

·         In infants, elderly individuals and those with neurological injury, urination may occur as an involuntary reflex. Thus they are not able to control their bladder.

·         In healthy individuals, the lower urinary tract has two discrete phases of activity: the storage  phase, when urine is stored in the bladder; and the voiding phase, when urine is released through the urethra.

·         At low bladder volumes, afferent firing is low, resulting in excitation of the outlet (the sphincter and urethra), and relaxation of the bladder. At high bladder volumes, afferent firing increases, causing a conscious sensation of urinary urge. When the individual is ready to urinate, he or she consciously initiates voiding, causing the bladder to contract and the outlet to relax. Voiding continues until the bladder empties completely, at which point the bladder relaxes and the outlet contracts to re-initiate storage.

·         The muscles controlling micturition are controlled by the autonomic and somatic nervous systems. During the storage phase the internal urethral sphincter remains tense and the detrusor muscle relaxed by sympathetic stimulation. During micturition, parasympathetic stimulation causes the detrusor muscle to contract and the internal urethral sphincter to relax. The external urethral sphincter (sphincter urethrae) is under somatic control and is consciously relaxed during micturition.

·         In the adult, the volume of urine in the bladder that normally initiates a reflex contraction is about 300-400 ml.

·         The impulses are sent to the spinal cord is modified by centres in the cerebral cortex.

·         The impulses from the brain cortex are sent back as efferent nerve impulse to the sacral region of the spinal cord and then to the external urinary sphincter muscles, which relaxes and thus urine flow from the bladder to urethra.

·         Injury to any of these leads to involuntary micturition (incontinence)

·         Polyuria is the condition of excessive urine output; oliguria is the condition of decreased urine output and anuria is the condition of nearly absent or absent urine output. Anuria is a sign of renal failure.

           

Mechanism of action of Renin 

 Renin-angiotensin-aldosterone System

·         Renin circulates in the blood stream and breaks down (hydrolyzes) angiotensinogen secreted from the liver into the peptide angiotensin I.

·         Angiotensin I is further cleaved in the lungs by an enzyme (ACE) which is found mainly in lungcapillaries) into angiotensin II, the most vasoactive peptide.

·         Angiotensin II  is the major active product of the renin-angiotensin system, binding to receptors on glomerular cells, causing these cells to contract along with the blood vessels surrounding them so is a potent constrictor of all blood vessels. The heart, trying to overcome this increase in its 'load', works more vigorously, causing the blood pressure to rise. Angiotensin II also acts on the adrenal glands and releases Aldosterone from the adrenal cortex, which stimulates the epithelial cells of the kidneys to increase re-absorption of salt and water, leading to raised blood volume and raised blood pressure. This system of hormones  also acts on the CNS to increase water intake by stimulating thirst, as well as conserving blood volume, by reducing urinary loss through the secretion of Vasopressin from the posterior pituitary gland.