Physiology of Excretion

Physiology of excretion

Major nitrogenous excretory substance in frog, rabbit and human is urea, i.e. these are ureotelic animals. The excretory physiology in these animals may be considered under two phases, viz urea synthesis and formation and excretion of urine.

Synthesis of urea in liver : Urea is formed in liver by two processes.

(1) Deamination      (2) Ornithine cycle

(1) Deamination : The amino acid is oxidised using oxygen. This result in removal of the amino group $\left(N{H}_2\right)$ and leaves pyruvic acid. the pyruvic acid can enter the Krebs cycle and be used as a source of energy in cell respiration. The amino group is converted to ammonia $\left(N{H}_3\right)$ during deamination. Deamination is also known as oxidative deamination.  

\mathop {{\begin{array}{*{20}{l}} #xA0{C{H_3}} \\ #xA0| \\ #xA0{CH - N{H_2} + \frac{1}{2}{O_2}} \\ #xA0| \\ #xA0{COOH} \end{array}}\xrightarrow{{}}}\limits_{\left( {{\text{Amino}}\,\,{\text{acid}}} \right)\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,} \mathop {{\begin{array}{*{20}{l}} #xA0{C{H_3}} \\ #xA0| \\ #xA0{CO + N{H_3}} \\ #xA0| \\ #xA0{COOH} \end{array}}}\limits_{\left( {{\text{Pyruvic}}\,{\text{acid}}} \right)}

With the help of a number of enzymes and energy of A.T.P. two molecules of ammonia are combined with $C{O}_2$ to form urea according to the ornithine cycle.

(2) Ornithine cycle (Kreb-Henseleit cycle) : In liver one molecule of $C{O}_2$ is activated by biotin and combines with two molecules of NH₃ in the presence of carbamyle phosphate synthatase enzyme (C.P.S.) and 2 ATP to form carbamyle phosphate and one molecule of $H_{2}O$ release. Carbamyle phosphate react with ornithine and form citrulline. Citrulin combines with another molecule of ammonia and form arginine. Arginine is broken into urea and ornithine in the presence of an enzyme arginase and water.

$2N{H}_3+C{O}_2\stackrel{\text{Arginase}}{\to }\underset{\text{(Urea)}}{N{H}_2-CO-N{H}_2+H_{2}O}$

Liver cells, thus, continuously remove ammonia and some $C{O}_2$ from blood and release urea into the blood. Kidneys continuously remove urea from the blood to excrete it in urine.

Urine formation : Urine formation occurs in the kidneys. It involves three processes glomerular filtration, reabsorption and tubular secretion.

(1) Ultra filtration (Starling’s hypothesis)

(i) It is passive process which takes place from the glomerulus into the Bowman&aposs capsule. The glomerular epithelium has various micropores (diameter = 50 – 100 nm or 0.05 – 0.1 $\mu$m) which increase the rate of filtration.

(ii) The non colloidal part of the plasma as urea, water, glucose, salts, vitamin, minerals, nitrogenous waste are forced out from the glomerular capillaries into the Bowman&aposs capsule by the high pressure of the blood in the glomerular capillaries. The pressure and resistence is high because the glomerular capillaries are narrower than the afferent renal arteries. Glomerular capillaries are about 50 times more permeable than capillaries elsewhere. Pressure highest in glomerular capillaries than in capillaries else where, produce more filtrate.    

(iii) The effective filtration pressure that causes ultrafiltration is determined by three pressures.

(a) Glomerular blood hydrostatic pressure (G.B.H.P.) : Hydrostatic pressure is force that a fluid under pressure exerts against the walls of its container.

G.B.H.P. = +70 mm Hg.

(b) Blood colloidal osmotic pressure (B.C.O.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.

B.C.O.P. = 30 mm Hg.

B.C.O.P. in other body capillaries is 25 mm Hg

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

C.H.P. = 20 mm Hg.

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.

      ਎.F.P. = G.B.H.P. – (B.C.O.P. + C.H.P.)

                 = 70 mmg – (30 mmg Hg + 20 mm Hg)

                   = 70 – 50

      ਎.F.P. = 20 mm Hg

$\bullet$ Net opposing filtration pressure

(N.O.F.P.) = B.C.O.P.+C.H.P.

                         = 50 mm Hg.

 Glomerular filtrate : The plasma fluid that filters out from glomerular capillaries into Bowman&aposs 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 filtrate or Nephric filtrate

= Blood – (Blood cells + Plasma protein)

                       or

= Blood – (R.B.Cs + W.B.Cs + platelets + plasma protein)

                       or

= Plasma – Protein

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 (R.P.F.)

R.P.F. = 670 ml.

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

Filtration fraction = $\frac{G.F.R.}{R.P.F.}$$=\frac{120}{670}=0.17$

(2) Selective reabsorption : Discovered by Richard and supporters.

Proximal convoluted tubule : P.C.T. is the pivotal site for reabsorption. Glucose, amino acid and $N{a}^{+}$, $K^{+}$ ions are reabsorbed by active transport. $C{l}^{-}$ are reabsorbed by passive transport following the positively charged ions.

Active uptake of ions reduces the concentration of the filtrate and an equivalent amount of water passes into the peritubular capillaries by osmosis. (Here 80% water is reabsorbed by passive transport. It is also known as obligatory water reabsorption). Most of the important buffer bicarbonate $\left(HC{O}_3^{-}\right)$ is also reabsorbed from the filtrate. P.C.T. absorb nearly 80�% of filtered bicarbonate. Some urea is reabsorbed by diffusion. The rest remain in the filtrate for removed in the urine.

Henle&aposs loop : See counter current mechanism.

Distal convoluted tubule : When the level of plasma water falls, the posterior pituitary lobe release the antidiuretic hormone (ADH) which increases the permeablity of the distal convoluted tubule and the collecting duct to water. Water is reabsorbed from the filtrate by osmosis and a reduced amount of concentrated urine is produced (Here 13% water is reabsorbed by facultative reabsorption)

The distal convoluted tubule and the collecting duct actively reabsorbed sodium from the filtrate under influence of the adrenal hormone aldosteron which makes their walls permeable to ions. The reabsorption of $N{a}^{+}$ brings about the uptake of an osmotically equivalent amount of water. But duct of Bellini is relatively impermeable to water. Bicarbonate ions are also reabsorbed in D.C.T.

(3) Tubular secretion : It occurs as under –

(i) Creatinine, hippuric acid and foreign substances (pigments, drugs including penicillin) are actively secreted into the filtrate in the PCT from the interstitial fluid. Hydrogen ions and ammonia $\left(N{H}_3\right)$ are also secreted into the PCT.

(ii) Potassium, hydrogen, $N{H}_4^{+}$ and $HC{O}_3^{-}$ ions are secreted by active transport, into the filtrate in the DCT.

(iii) Urea enters the filtrate by diffusion in the thin region of the ascending limb of Henle&aposs loop.

Removal of $H^{+}$ and $N{H}_4^{+}$ from the blood in the PCT and DCT helps to maintain the pH of the blood between 6 to 8. Any variation from this range is dangerous.

Tubular secretion probably plays only a minor role in the function of human kidneys, but in animals, such as marine fish and desert amphibians which lack glomeruli and Bowman&aposs capsules, tubular secretion is the only mode of excretion. When the blood pressure, and consequently the filtration pressure, drop below a certain level, filtration stops and urine is formed by tubular secretion only.

High threshold substances : Such substances are absorbed almost all. Example – Sugar, amino acids, vitamins, HCO₃^– and Na⁺ etc.

Low threshold substances : They are absorbed in low concentration. Example – Urea, phosphate, uric acid, H⁺, K⁺ .

Non threshold substances : They are not reabsorbed. Example – Creatinine and hippuric acid.

Diuretic substances : Normally, the amount of urine formed depends on the intake of water, dietary constituents, environmental temperature, mental and physiological states of the person. However, there are some substances which increase the volume of urine to be excreted, these substances are called diuretic substances. Exmaple – Tea, Coffee, alcohol etc.

Mechanism of urine concentration (Counter current mechanism of urine concentration) : Mammals form hypertonic urine. The urine is made hypertonic with the help of counter current multiplier system. This process takes place in the Henle&aposs loop and vasa recta and it involves mainly $N{a}^{+}$ and $C{l}^{-}$. In P.C.T. urine is isotonic. The descending limb of loop of Henle is permeable to water. Its surrounding tissue fluid is hypertonic. Hence, the water moves out and the $N{a}^{+}$ and $C{l}^{-}$ moves in the descending limb by passive transport. Therefore, the filtrate in the descending limb finally becomes hypertonic.

The ascending limb of the Henle&aposs loop is impermeable to the water. The $N{a}^{+}$ and $C{l}^{-}$ moves out by active transport. Hence the filtrate finally becomes hypotonic. The $N{a}^{+}$ and $C{l}^{-}$ re-enter into the descending limb of the Henle&aposs loop. The collecting duct always passes through the hypertonic tissue fluid. Hence, water comes out osmotically making the filtrate hypertonic. Now in collecting duct glomerular filtrate is known as urine. Term urine first time use in collecting duct.

Urine

The fluid and dissolved waste substances excreted by the kidneys constitute urine.

Quantity : An adult man normally passes about 1 to 1.8 litres of urine in 24 hours. The volume of urine depends upon (i) the fluid intake, (ii) level of physical activity, (iii) type of food taken and (iv) environmental temperature increase urine output. Less fluid intake and profuse sweating due to heavy physical work and high temperature reduce urine output. Certain substances, such as tea, coffee and alcohol, increase urine output. These are said to be diuretic.

Physical properties : Urine is transparent yellowish fluid, but becomes turbid (cloudy) on standing, its colour depending on its concentration. Its colour is due to a pigment urochrome derived from the breakdown of haemoglobin from the worn-out RBCs. Colour of the urine is altered by certain materials taken such as beet, vitamin B complex and some drugs diseases. It is hypertonic to blood plasma. Its specific gravity ranges between 1.001 to 1.035, being slightly higher than that of water. Its pH is 6. It depends on the diet. High protein food and fruits increase acidity whereas vegetables increase alkalinity. Urine has a characteristic unpleasant odour. If allowed to stand, urea is degraded by bacteria to ammonia which imparts a strong smell to urine.

Chemical composition : Urine consists of water and organic and inorganic substances. Water alone forms about 95% of it, other substances form only 5%. The organic substances are mainly nitrogenous organic compounds include urea, uric acid, creatinine and hippuric acid. Of these, urea is the principal component of human urine. The non nitrogenous organic compounds include vitamin C, oxalic acid, phenolic substances include ammonia, and mineral salts such as chlorides, sulphates and phosphates of sodium, potassium, calcium and magnesium. Sodium chloride is the principal mineral salt of the urine. Urine also contains some other substances, such as pigments and drugs, and some epithelial cells, leucocytes, mucin, enzymes, and hormones.

 Abnormal materials : Presence of proteins (albumins), bile salts, bile pigments, ketone bodies, blood, pus, microbes and more than a trace of glucose in the urine is pathological condition. Presence of glucose, protein, blood, ketone bodies and pus in the urine is called glucosurea, proteinuria, haematuria, ketonuria and pyuria respectively.

 Renal threshold : A negligible amount of glucose is present in the urine. The highest concentration of a substances in the blood upto which it is fully reabsorbed from the glomerular filtrate is called its threshold. If its concentration in the blood exceeds its renal threshold, some of the filtered out substance is not reasborbed and is excreted in the urine. For example, the renal threshold of glucose is 180 mg. per 100 ml. of blood. If its blood level exceeds 180 mg., some of the filtered out glucose is not reabsorbed and is passed in urine.

Conduction of urine and Micturition : Urine is produced and drained continuously by the nephrons into the renal pelvis. From here, it is carried down the ureters by peristaltic waves into trigonum vesicae and then into the body of the urinary bladder. The bladder serves to store the urine temporarily and also to pass it out at suitable intervals. The process of passing out urine from the urinary bladder is called urination or micturition, As urine collects, the muscular walls of the bladder distend to accommodate it. Distension of its walls stimulates the sensory nerve endings in the bladder wall and this sets up reflexes, which cause an urge to pass out urine. During the discharge of the urine, the bladder and urethral sphincters relax and the smooth muscles of the bladder wall gradually contract. This slowly drives the urine from the bladder through the urethra to the exterior. Reflux of the urine into the ureters is prevented because the terminal parts of the ureters pass obliquely through the bladder wall and are consequently closed when the bladder wall contracts around them. Relaxation and contraction of the urinary bladder are caused by impulses from the sympathetic and parasympathetic nerve fibres.

Micturition may be voluntarily postponed for some time until the pressure in the bladder rises too high to control. Micturition may also be voluntarily achieved even before sufficient urine has accumulated in the bladder. Normally an urge for micturition starts when the bladder is a little more than halffull of urine.

Hormonal control of renal function

Hormonal controls of the kidney function by negative feedback circuits can be identified :

(1) Control by antidiuretic hormone (ADH) : ADH, produced in the hypothalamus of the brain and released into the blood stream from the pituitary gland, enhances fluid retention by making the kidneys reabsorb more water. The release of ADH is triggered when osmoreceptors in the hypothalamus detect an increase in the osmolarity of the blood above a set point of 300 mosm L^𠄱. In this situation, the osmoreceptor cells also promote thirst. Drinking reduces the osmolarity of the blood, which inhibits the secretion of ADH, thereby completing the feedback circuit.

(2) Control by Juxtaglomerular apparatus (JGA) : (Low Blood pressure triggers the Reninangiotension pathway) JGA operates a multihormonal Renin-Angiotensin-Aldosterone System (RAAS). The JGA responds to a decrease in blood pressure or blood volume in the afferent arteriole of the glomerulus and releases an hormone, renin into the blood stream. In the blood, renin initiates chemical reactions that convert a plasma protein, called angiotensinogen, to a peptide, called angiotensin II, which works as a hormone. Angiotensin II increases blood pressure by causing arterioles to constrict. It also increases blood volume in two ways – firstly, by signaling the proximal convoluted tubules to reabsorb more NaCl and water, and secondly, by stimulating the adrenal gland to release aldosterone, a hormone that induces the distal convoluted tubule to reabsorb more Na⁺ and water. This leads to an increase in blood volume and pressure, completing the feedback circuit by supporting the release of renin.

(3) Parathormone : The hormone increases blood Ca⁺⁺ (Hypercalcium) and decreases PO₄ accordingly, it increases absorption of Ca⁺, increases excretion of PO₄.

(4) Thyrocalcitonin : It increases excretion of Ca⁺⁺ in the kidney.

(5) Prostaglandin : The renal pyramids produce fatty acids of prostaglandins (P.G.) which participates in blood pressure regulation.

(6) Erythropoeitin : It is secreted by juxtaglomerular apparatus and plays an important role in erythropoeisis (blood production).

Homeostatic regulatory functions of kidneys

By continuously eliminating metabolic wastes and other impurities, and even the surplus quantity of useful materials from blood plasma in the form of urine, kidneys play a vital role in homeostasis. Kidneys also operate certain other homeostatic regulatory mechanisms. Proper maintenance of the internal environment is knows as homeostasis. All regulatory functions of kidneys can be enumerated as follows –

(1) Osmoregulation : Being the universal solvent, water is the actual vehicle in ECF to transport materials between various parts of body. Water volume in ECF tends to vary considerably due to several reason, such as drinking, perspiration, diarrhoea, vomiting, etc. As described in previous pages, the kidneys maintain the water balance in ECF by diluting or concentrating urine.

(2) Regulation of osmotic pressure : Osmolality of cytoplasm is mainly due to proteins and potassium and phosphate ions, whereas that of the ECF is mainly due to sodium, chloride and bicarbonate ions. Inspite of marked difference in chemical composition, the two fluids – intracellular (cytoplasm) and extracellular (interstitium) – must be isotonic, because if ECF becomes hypotonic, cells will absorb water, swell retaining apropriate number, mainly of sodium and chloride ions, kidneys maintain the normal osmolality of ECF.

(3) Regulation of pH : Concentration of hydrogen ions (NaH₂ PO₄) in ECF is to be regulated at a constant value usually expressed as pH (minus log of H⁺). The normal pH of ECF is about 7.4. A low pH, i.e. a high H⁺ concentration causes acidosis, while a high pH, i.e. a low H⁺ concentration causes alkalosis. Both of these conditions severely affect cellular metabolism. Several special control systems, therefore, operate in the body to prevent acidosis and alkalosis. These system are called acid-base buffer system. Kidneys play a key role in maintenance and operation of these systems. Further, the kidneys regulate hydrogen ion concentration in ECF by excreting acidic or basic urine.

(4) Regulation of electrolyte concentrations in ECF : The kidneys regulate, not only the total concentrations of water and electrolytes in ECF, but also the concentrations of individual electrolytes separately. This regulation is complex and is accomplished by tubular reabsorption and secretion under the control of hypothalamic and adrenal hormones.

(5) Regulation of RBC-count in blood : In oxygen deficiency (hypoxia), kidneys secrete an enzyme into the blood. This enzyme reacts with plasma globulin to form erythropoietin. The latter substance stimulates bone marrow to produce more RBCs for enhancing O₂-intake in lungs.

(6) Regulation of renal blood flow : See (R.A.A.S.).

Disorders of kidneys.

(1) 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.

(2) Glomerulonephritis : It is the inflammation of glomeruli. It is caused by injury to the kidney, bacterial toxins, drug reaction, etc. Proteins and R.B.Cs pass into the filtrate.

(3) 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.

(4) 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.

(5) Kidney stone (Renal calculus) : It is formed by precipitation of uric acid or oxalate. It blocks the kidney tubule. It causes severe pain (renal colic) in the back, spreading down to thighs. The stone may pass into the ureter or urinary bladder and may grow, and cause severe pain of blackade. When in bladder, the patient experiences frequent and painful urination and may pass blood in the urine. Surgery may be needed to remove stone and relieve pain.

(6) Kidney (Renal) failure (RF) : Partial or total inability of kidneys to carry on excretory and salt-water regulatory functions is called renal or kidney failure. Result kidney failure leads to (i) uremia, i.e., an excess of urea and other nitrogenous wastes in the blood (G.ouron = urine, haima-blood) (ii) Salt-water imbalance and (iii) stoppage of erythropoietin secretion.

Causes : Many factors can cause kidney failure. Among these are tubular injury, infection, bacterial toxins, glomerulonephritis (inflammation of glomeruli) arterial or venous obstruction, fluid and electrolyte depletion, intrarenal precipitation of calcium and urates, drug reaction, heammorrhage, etc.

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. dia = = 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^oC 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&aposs blood, and mixed with an antiheparin 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.

Kidney (Renal) Transplantation

Meaning : Grafting a kidney from a compatible donor to restore kidney functions in a recipient suffering from kidney failure is called renal transplantation.

History : First kidney transplant was performed between identical twins in 1954 by Dr. Charles Hufnagel, a Washington surgeon, India&aposs first kidney transplant was done on December 1, 1971 at Christian Medical College, Vellore, Tamilnadu. The recipient was a 35 years old person Shaninughan.

Eligibility : All patients with terminal renal failure are considered eligible for kidney transplantation, except those at risk from another life-threating disease.

Donors : A living donor can be used in a kidney transplant. It may be in identical twin, a sibling, or a close relative. If the living donors are not available, a cadaveric donor may be used (cadaver is a dead body). Over half of the kidney transplants are from cadavers.

Success rate : A kidney transplant from an identical twin, called isogeneic graft or isograft, is always successful. A renal transplant from a sibling or a close relative or a cadaver, termed allogeneic graft or homograft, is usually successful with the use of an immunosupressant that prevents graft rejection by body&aposs immune response. Many renal transplant recipients are known to have retained functional grafts for over 20 years. Earlier, renal transplantation was limited to patients under 55 years. Now, however, with better techniques, kidney grafting has been done in selected patients in the 7^th decade of life.

Pretransplant preparation : It includes haemodialysis to ensure a relatively normal metabolic state, and provision of functional, infection-free lower urinary tract.

Donor selection and kidney preservation : A kidney donor should be free of hypertension, diabetes, and malignancy. A living donor is also carefully evaluated for emotional stability, normal bilateral renal function, freedom from other systematic disease, and histocompatibility. Cadaveric kidney is obtained from previously healthy person who sustained brain death but maintained stable cardiovascular and renal function. Following brain death, kidneys are removed as early as possible, flushed with special cooling solutions, such as mannitol and stored in iced solution. Preserved kidneys usually function well if transplanted within 48 hours.

Recipient-Donor Matching : Recipient and donor are tested for 3 factors :

(1) Blood groups : Recipient&aposs blood group should be compatible with donor&aposs blood group.

(2) Human leucocyte antigen (HLA) : It is a genetic marker located on the surface of leucocytes. A person inherits a set of 3 antigens from the mother and three from the father. A higher number of matching antigens increases the chances that the kidney graft will last for a long time.

(3) Antibodies : Small samples of recipient&aposs and donor&aposs blood are mixed in a tube. If no reaction occurs, the patient will be able to accept the kidney.

Transplant procedure : Transplantation is done under general anaesthesia. Operation takes 3 or 4 hours. Cut is given in the lower abdomen. Donor&aposs kidney is transplanted retroperitonealy in the iliac fossa. Artery and vein of new kidney are connected to the iliac artery and vein of the recipient. Ureter of the new kidney is connected to the urinary bladder of the recipient. Often the new kidney starts producing urine as soon as blood flows through it, but sometimes it may take a few weeks before it starts working. A week&aposs stay in the hospital is necessary to recover from surgery, and longer if there are complications.

The new kidney takes over the work of two failed kidneys. Unless they are causing infection or high blood pressure, the old kidneys are left in place.

Immunosupression : Immunosupression means to depress the immune response of the recipient to graft rejection. Prophylactic immunosuppressive therapy is started just before or at the time of renal transplantation. An ideal immunosuppressant suppress immunity against foreign tissue but maintains immunity against infection and cancer. The drug, named cyclosporin, in such an immunosupressant. Use of antiserum to human lymphocytes is equally useful. It destroys T-cell mediated immune responses, but spares humoral antibody responses.

Accessory excretory organs  

(1) Skin : Many aquatic animals, such as Hydra and starfish, excrete ammonia into the surrounding water by diffusion through the body wall. In land animals, the skin is often not permeable to water. This is an adaptation to prevent loss of body&aposs water. Mammalian skin retains a minor excretory role by way of its sudoriferous, or sweat glands and sebaceous, or oil glands.

(i) Sweat gland : Sweat glands pass out sweat. The latter consists of water containing some inorganic salts (chiefly sodium chloride) and traces of urea and lactic acid. It also contains very small amounts of amino acids and glucose.

(ii) Sebaceous glands : Oil glands pass out sebum that contains some lipids such as waxes, sterols, other hydrocarbons and fatty acids. 

(2) Lungs : Carbon dioxide and water are the waste products formed in respiration. Lungs remove the $C{O}_2$ and some water as vapour in the expired air. Lungs have access to abundant oxygen and oxidise foreign substances, thus causing detoxification and also regulate temperature.

(3) Liver : Liver changes the decomposed haemoglobin of the worn-out red blood corpuscles into bile pigments, namely, bilirubin and biliverdin. These pigments pass into the alimentary canal with the bile for elimination in the faeces. The liver also excretes cholesterol, steroid hormones, certain vitamins and drugs via bile.

(4) Large intestine : Epithelial cells of the colon transfer some inorganic ions, such as calcium, magnesium and iron, from the blood into the cavity of the colon for removal with the faeces.

(5) Saliva : Heavy metals and drugs are excreted in the saliva.

(6) Gills : Gills remove CO^­₂ in aquatic animals. They also excrete salt in many bony fish.

Osmoregulation.

The regulation of solute movement, and hence, water movement, which follows solutes by osmosis, is known as osmoregulation. Osmosis may be defined as a type of diffusion where the movement of water occurs selectively across a semipermeable membrane. It occurs whenever two solutions, separated by semipermeable membrane (the membrane that allows water molecules to pass but not the solutes) differ in total solute concentrations, or osmolarity. The total solute concentration is expressed as molarity or moles of solute per litre of solution. The unit of measurement for osmolarity is milliosmole per litre (mosm L^𠄱). If two solutions have the same osmolarity, they are said to be isotonic. When two solutions differ in osmolarity, the solution with higher concentration of solute is called hypertonic, while the more dilute solution is called hypotonic. If a semipermeable membrane separates such solutions, the flow of water (osmosis) takes place from a hypotonic solution to a hypertonic one.

Osmoconformers are the animals that do not actively control the osmotic condition of their body fluids. They rather change the osmolarity of body fluids according to the osmolarity of the ambient medium. All marine invertebrates and some freshwater invertebrates are strictly osmoconformer. Osmoconformers show an excellent ability to tolerate a wide range of cellular osmotic environments.

Osmoregulators, on the other hand, are the animlas that maintain internal osmolarity, different from the surrounding medium in which they inhabit. Many aquatic invertebrates are strict or limited osmoregulators. Most vertebrates are strict osmoregulators, i.e. they maintain the composition of the body fluids within a narrow osmotic range. The notable exception, however, are the hagfish (Myxine sp., a marine cyclostome fish) and elasmobranch fish (sharks and rays).

Osmoregulators must either eliminate excess water if they are in hypotonic medium or continuously take in water to compensate for water loss if they are in a hypertonic situation. Therefore, osmoregulators have to spent energy to move water in or out and maintain osmotic gradients by manipulating solute concentrations in their body fluids.