Urine Formation and Kidney Functions

Urea Formation

Occur ill liver through the Ornithine cycle or Kreb's Henseleit cycle.

For the synthesis of one molecule of urea 3 ATP are consumed.

One molecule of urea is formed by the 2 mole of ammonia and 1 mole of CO₂. 1 mol of ammonia come from deamination of fat and other mol of ammonia comes from aspartic-acid.

Formation of citrulline occurs in mitochondria. 

Urine Formation

Urine formation involves three main processes namely, glomerular filtration, reabsorption and secretion.

The first step in urine formation is the filtration of blood, which is carried out by the glomerulus and is called glemerular filtration.

On an average, 1100-1200 ml of blood is filtered by the kidneys per minute which constitute roughly 1/5th of the blood pumped out by each ventricle of the heart in a minute.

The glomerular capillary blood pressure causes filtration of blood through 3 layers, i.e., the endothelium of glomerular blood vessels, the epithelium of Bowman's capsule and a basement membrane between these two layers. The epithelial cells of Bowman's capsule called podocytes are arranged in an intricate manner so as to leave some minute spaces called filtration slits or slit pores. Blood is filtered so finely through these membranes, that almost all the constituents of the plasma except the proteins pass onto the lumen of the Bowman's capsule. Therefore, it is considered as a process of ultra filtration.

The amount of the filtrate formed by the kidneys per minute is called glomerular filtration rate (GFR). GFR in a healthy individual is approximately 125 ml/minute, i.e., 180 litres per day.

The kidneys have built-in mechanisms for the regulation of glomerular filtration rate. One such efficient mechanism is carried out by juxta glomerular apparatus GGA). JGA is a special sensitive region formed by cellular modifications in the distal convoluted tubule and the afferent arteriole at the location of their contact. A fall in GFR can activate the JG cells to release renin which can stimulate the glomerular blood flow and thereby the CPR back to normal. 

A comparison of the volume of the filtrate formed per' day (180 litres per day) with that of the urine released (1.5litres), suggest that nearly 99 per cent of the filtrate has to be reabsorbed by the renal tubules. This process is called reabsorption. The tubular epithelial cells in different segments of nephron perform this either by active or passive mechanisms.

Substances like glucose; amino adds, Na⁺, etc, in the filtrate are reabsorbed actively whereas the nitrogenous wastes are absorbed by passive transport. Reabsorption of water also occurs passively in the initial segments of the nephron.

During urine formation, the tabular cells secrete substances like H⁺, K⁺ and ammonia into the filtrate. Tubular secretion is also an important step in urine formation as it helps in the maintenance of ionic 'and acid base balance or body fluids.

Proximal Convoluted Tubule (PCT): PCT is lined by simple cuboidal brush border epithelium which increases the surface area for reabsorption. Nearly all of the essential nutrients, and 70-80 per cent of eletrolytes and water are reabsorbed by this segment. PCT also helps to maintain the pH and ionic balance of the body fluids by selective secretion of hydrogen ions. Ammonia and potassium ions into the filtrate and by absorption of HCO₃^- from it.

Henle's Loop: Reabsorption in this segment is minimum, However, this region plays a significant role in the maintenance of high osmolarity of medullary interstitial fluid. The descending limb of loop of Henle is permeable to water but almost. impermeable to electrolytes. This concentrates the filtrate as it moves' down.

Distal Convoluted Tubule (OCT): Conditional reabsorption of Na⁺ and water takes place in this segment. OCT is also capable of reabsorption of HCO₃^- and selective secretion of hydrogen and potassium ions and NH₃ to maintain the pH and sodium-potassium balance in blood.

Collecting Duct: This long duct extends from the cortex of the kidney to the inner parts of the medulla. Large amounts of water could be reabsorbed from this region to produce a concentrated urine. This segment allows passage of small amounts of urea into the medullary interstitium to keep up the osmolarity. It also plays a role in the maintenance of pH and ionic balance of blood by the selective secretion of H⁺ and K⁺ ions. 
 

Mechanism of Concerntration of the Filtrate

A counter current mechanism operates between the two limbs of the loop of Henle and those of vasa recta (capillary parallel to Henle's loop). The filtrate gets concentrated as it moves down the descending limb but is diluted by the ascending limb. Electrolytes and urea are retained in the interstitium by this arrangement. 

DCT and collecting duct concentrate the filtrate about four times, i.e., from 300 mOsmol L^-1 to 1200 mOsmol L^-1, an excellent mechanism of conservation of water.
 

Regulation of Kidney Function

The functioning of the kidneys is efficiently monitored and regulated by hormonal feedback mechanisms involving the hypothalamus, JGA and to a certain extent, the heart.

Osmoreceptors in the body are activated by changes in blood volume, body fluid volume and ionic concentration. An excessive loss of fluid from the body can activate these receptors which stimulate the hypothalamus to release antidiuretic hormone (ADH) or vasopressin from the neurohypophysis. ADH facilitates water reabsorption from latter parts of the tubule, thereby preventing diuresis. An increase in body fluid volume can switch off the osmoreceptors and suppress the ADH release to complete the feedback. ADH can also affect the kidney function by its constrictory effects on blood vessels. This causes an increase in blood pressure. An increase in blood pressure can increase the glomerular blood flow and thereby the GFR.

The JGA plays a complex regulatory role. A fall in glomerular blood flow I glomerular blood pressure/GFR can activate the JG cells to release renin which converts angiotensinogen in blood to angiotensin I and further to angiotensin II. Angiotensin II, being a powerful vasoconstrictor, increases the glomerular blood pressure and thereby GFR. Angiotensin II also activates the adrenal cortex to release Aldosterone. Aldosterone causes reabsorption of Na⁺ and water from the distal parts of the tubule. This also leads to an increase in blood pressure and GFR. This complex mechanism is generally known as the Renin Angiotensin mechanism.

An increase in blood flow to the atria of the heart can cause the release of Atrial Natriuretic Factor (ANF). ANF can cause vasodilation (dilation of blood vessels) and thereby decrease the blood pressure. ANF mechanism, therefore, acts as a check on the renin-angiotensin mechanism.

Disorders of the Excretory System

Malfunctioning of kidneys can lead to accumulation of urea in blood, a condition called uremia, which is highly harmful and may lead to kidney failure. In such patients, urea can be removed by a process called hemodialysis.

Kidney transplantation is the ultimate method in the correction of acute renal failures (kidney failure).

Renal calculi: Stone or insoluble mass of crystallised salts (oxalates, etc.) formed within the kidney.

Glomerulonephritis: Inflammation of glomeruli of kidney.

Pyelonephritis: It is an inflammation of renal pelvis, calyces and interstitial tissue (G.pyelos = trough, tub; nephros = kidney; itis = inflammation). It is due to local bacterial infection. Bacteria reach here via urethra and ureter. Inflammation affects the countercurrent mechanism, and the victim fails to concentrate urine. Symptoms of the disease include pain in the back, and frequent and painful urination.

Cystitis: It is the inflammation of urinary bladder (G.kystis = bladder, -itis = inflammation). It is caused by bacterial infection. Patient has frequent, painful urination, often with burning sensation.

Uremia: Uremia is the presence of an excessive amount of urea in the blood. It results from the decreased excretion of urea in the kidney tubules due to bacterial infection (nephritis) or some mechanical obstruction. Urea poisons the cells at high concentration

Artificial kidney: Artificial kidney, called haemodialyser, is a machine that is used to filter the blood of a person whose kidneys are damaged. The process is called haemodialysis. It may be defined as the separation of small molecules (crytalloids) from large molecules (colloids) in a solution by interposing a semipermeable membrane between the solution and water (dialyzing solution). It works on the principle of dialysis, i.e. diffusion of small solute molecules through a semipermeable membrane (G. din = through, lyo = separate). Haemodialyser is a cellophane tube suspended in a salt-water solution of the same composition as the normal blood plasma, except that no urea is present. Blood of the patient is pumped from one of the arteries into the cellophane tube after cooling it to 0°C and mixing with an anticoagulant (heparin). Pores 'of the cellophane tube allow urea, uric acid, creatinine, excess salts and excess H⁺ ions to diffuse from the blood into the surrounding solution. The blood, thus purified, is warmed to body temperature, checked to ensure that it is isotonic to the patient's blood, and mixed with an anti-heparin to restore its normal clotting power. It is then pumped into a vein of the patient. Plasma proteins remain in the blood and the pores of cellophane are too small to permit the passage of their large molecules. The use of artificial kidney involves a good deal of discomfort and a risk of the formation of blood clots. It may cause fever, anaphylaxis, cardiovascular problems and haemorrhage. Kidney transplant is an alternative treatment. 

Note:
Human kidneys can produce urine nearly four times concentrated than the initial filtrate formed.

The process of release of urine is called micturition and the neural mechanisms causing it is called the micturition reflex.

An adult human excretes, on an average, 1 to 1.5 litres of urine per day.

The urine is a light yellow coloured watery fluid which is slightly acidic (pH-6.0) and has a characterestic odour.

On an average, 25-30 gm of urea is excreted out per day.

Presence of glucose (Glycosuria) and ketone bodies. (Ketonuria) in urine are indicative of diabetes mellitus.

Our lungs remove large amounts of CO₂ (18 litres/ day) and also significant quantities of water every day.

Liver, the largest gland in our body, secretes bile- containing substances like bilirubin, biliverdin, cholesterol, degraded steroid hormones, vitamins and drugs. Most of these substances ultimately pass out along with digestive wastes.

Sebaceous glands eliminate certain substances like sterols, hydrocarbons and waxes through sebum. This secretion provides a protective oily covering for the skin.

Gout: It is hereditary condition which is associated with high level of uric acid in blood.'

Ptosis: Displacement of kidney.

Urease

Urea NH₃ + CO₂

Abnormal constituent of urine - (i.e. Not present in normal condition)

Protein - If protein is present in urine it may be due to infection or injury in kidney. (Mainly albumin is filtered)

Blood -Due to infection and injury of kidney blood may appear in urine.

Sugar - In diabetes mellitus sugar appear in urine.

Bile or bile pigment - In jaundice bile pigment appear in urine.

Ketone bodies - In starvation and diabetes, ketone bodies appear in urine.

Glomerular blood hydrostatic pressure (G.B.H.P.):  

Hydrostatic pressure is force that a fluid under pressure exerts against the walls of its container.

Blood colloidal osmotic pressure (B.CO.P): The B.C.O.P. is the osmotic pressure created in the blood of glomerular capillaries due to plasma proteins albumin, globulin, and fibrinogen. It resists the filtration of fluid from the capillaries.

Capsular hydrostatic pressure (C.H.P): C.H.P. is the pressure caused by fluid (filtrate) that reaches into Bowman's capsule and resists filtration.

Effective filtration' pressure (E.F.P.)/Net filtration pressure (N.F.P.): E.F.P. is glomerular blood hydrostatic pressure minus the colloidal osmotic pressure of blood and capsular hydrostatic pressure.

Glomerular filtrate: The plasma fluid that filters out from glomerular capillaries into Bowman's capsule of nephrons is called glomerular filtrate. It is a non colloidal part and possess urea, water, glucose, amino acid, vitamins, fatty acid, uric acid, creatin, creatinine, toxins, salts etc.

R.B.Cs, W.B.Cs, platelets and plasma proteins are the colloidal part of the blood and 'do not filtered out from glomerulus. Glomerular filtrate is isotonic to blood plasma.       

Glomerular filtration rate (G.F.R.): G.F.R. is the amount of filtrate formed per minute in all nephrons of the paired kidney. There is a sexual difference. In male the rate is 120 - 125 ml/min, in female it is 110 ml/min. G.F.R. is affected by volume of circulating blood, neural activity, stretch response to pressure of the wall of the arteriole.

180 litre of filtrate is formed per day, out of It only 1.5 litre of-urine is produced per day which is 0.8% of the total filtrate.

Renal plasma flow: About 1250 ml (25% of cardiac output or total blood) blood circulates through kidneys each minute and of this blood, about 670 ml is the plasma. The latter is called the renal plasma flow (RP.F.)

Filtration fraction: This is the ratio of G.F.R to RP.F., and it is called filtration fraction.

Filtration fraction = G.F.R/R.P.F = 120/670=0.17
 

Summary of Events Occurring in a Nephron

Differences between Male and Female Urethra

Excretory Organs of Different Organisms

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