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In this article we will discuss about the kidneys:- 1. Introduction to Kidney 2. Functions of Kidney 3. Urine Formation 4. Mechanism of Action of Diuretics 5. Renal Function Tests 6. Congenital Tubular Function Defects 7. Uremia 8. The Artificial Kidney 9. Hormones.
Contents:
- Essay on the Introduction to Kidney
- Essay on the Functions of Kidney
- Essay on the Urine Formation in Kidney
- Essay on the Mechanism of Action of Diuretics
- Essay on the Renal Function Tests
- Essay on the Congenital Tubular Function Defects in Kidney
- Essay on the Uremia –Clinical Kidney Condition
- Essay on the Artificial Kidney
- Essay on the Hormones of the Kidney
Essay # 1. Introduction to Kidney:
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A large number of waste products are produced in the body as a result of metabolic activities. The main waste products are carbon dioxide, water, and nitrogenous compounds. The retention of these products produces a harmful effect on the normal health.
Therefore, the removal of these products from the body is a must. Carbon dioxide is removed mainly through lungs and water as well as nitrogenous compounds are removed through urogenital system. The kidneys are the most important component of this system.
The kidneys are two in number, usually bean shaped, and exist behind the peritoneum on either side of the vertebral column extending from the 12th thoracic to the 3rd lumbar vertebra. Each kidney weighs about 120-170 grams and is about 11-13 cms. long, the left being larger than the right one.
Each kidney is found to consist of two main parts by section. The outer part is called cortex and the inner one is medulla. The cortex consists of a large number of glomeruli and convoluted tubules. The medulla is composed of renal tubules projecting into a cavity towards the inner region of the kidney called the pelvis, the region where the renal artery and vein enters and leaves the kidney respectively.
Nephron –Basic Unit od Kidney:
It is a functional basic unit of kidney. Each kidney is provided with about one million nephrons containing the glomerulus and the tubule. The glomerulus is a network of afferent and efferent capillaries.
Each glomerulus is surrounded by a double-walled epithelial sac known as Bowman ‘s Capsule which leads to the tubule which is divided into three parts—proximal convoluted tubule, loop of Henle, and the distal convoluted tubule.
The Proximal Convoluted Tubule (PCT) is about 45 mm long and 50 mm in diameter. This lies in the cortex along with glomerulus. Its lumen is continuous with that of the Bowman’s Capsule. It consists of cells with scalloped outline and brush border. The brush border is formed by numerous microvilli which increases the surface enormously for absorption.
The loop of Henle consists of three parts—the descending limb, a thin segment, and an ascending limb. The proximal convoluted tubule opens into the descending limb which is continued into the thin segment from where the ascending limb arises. The whole loop of Henle is lined by a single layer of flattened epithelial cells.
The ascending limb of the loop of Henle continues into the distal convoluted tubule (DCT) which finally opens into a collecting tubule or duct which carries the urine to the renal pelvis from where it is carried to the bladder by the ureter.
The distal convoluted tubule commences near the pole of the glomerulus and establishes a close proximity to the afferent arteriole of its parent glomerulus. The DCT contains cuboidal epithelium.
Nephrons are mainly of two types—cortical and juxtamedullary. The loop of Henle of the juxtamedullary is long and dips deep into the substance of the medulla. But the loop of Henle of cortical is short and only a very small part of it dips into the medullary tissue and the greater part remains embedded in the cortical substances.
Moreover, the glomeruli of the juxtamedullary lie very close to the medulla while those of cortical lie close to the surface of the kidney. The juxtamedullary nephrons constitute 20 per cent of nephrons, while the cortical nephrons constitute 80 per cent of the total nephrons. These two types of nephrons have the same common function.
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Blood Supply of the Kidneys:
The short renal artery arising from the abdominal aorta supplies the blood to the kidney. The renal artery after entering the kidney divides into a number of arterioles—the afferent arterioles which further branch into capillaries and enter into each glomerulus.
The capillaries then join to form another arteriole—the efferent arteriole which opens into another set of capillaries called peritubular capillaries surrounding the proximal tubule, the loop of Henle, and the distal tubule. Ultimately, the capillary set opens into a venule which joins with other venules to form the renal vein. The renal vein then opens into the inferior vena cava.
Blood Flow to Kidney through the Nephron:
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The blood flows through both the kidneys of an adult weighing 70 kg at the rate of about 1200 ml/mt. The portion of the total cardiac output (about 560 ml/ mt.) which passes through the kidneys is called the renal fraction. This is about 560/1200 ml per minute, i.e., about 21 per cent.
There are two sets of capillaries—the glomerulus and the peritubular. These two capillaries are separated from each other by the efferent arteriole which contributes sufficient resistance to blood flow. The glomerular capillary bed provides a high pressure of about 70 mm Hg, while the peritubular bed provides a low pressure about 13 mm Hg.
The pressures in the artery and vein are 100 mm of Hg. and 8 mm of Hg respectively. The high pressure in the glomerulus exerts the filtering of fluids continually into the Bowman’s Capsule. The low pressure in the peritubular capillary system, on the other hand, functions in the same way as the usual venous ends of the tissue capillaries with the fluid being absorbed continually into the capillaries.
Essay # 2. Functions of Kidney:
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a. Kidney eliminates excess of certain nutrients such as sugar and amino acids when their concentration increases in the blood.
b. It removes certain non-volatile waste products such as urea, uric acid, creatinine, and sulphates, etc. from the body.
c. It eliminates certain foreign or toxic substances such as iodides, pigments, drugs, and bacteria, etc. from the blood.
d. It regulates hydrogen ion concentration of the blood by removing excess of nonvolatile acids and bases.
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e. It maintains the osmotic pressure of the blood by regulating the excretion of water and inorganic salts and thus preserves the constant volume of the circulating blood.
f. It regulates the arterial blood pressure by causing the secretion of the hormone renin.
g. It maintains the erythrocyte production by excreting the secretion of the hormone erythropoietin.
Essay # 3. Urine Formation in Kidney:
The regulatory activities of kidneys form urine as a by-product. Urine formation involves three main steps—the glomerular filtration, the tubular reabsorption, and the tubular secretion.
a. Glomerular Filtration (Ultrafiltration):
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Glomerulus filters out substances of low molecular weight from the blood with the retention of substances of high molecular weight, especially the proteins. Therefore, proteins are retained in the glomeruli and are not normally found in urine. If protein is detected in the urine, it indicates the kidney damage or other disease which effect the glomerular membrane.
In normal adult, two million nephrons filter one litre of blood each minute to give about 1200 ml of glomerular filtrate (primary urine) at Bowman’s Capsule. Therefore, the Glomerular Filtration Rate (GFR) in adult is about 120 ml per minute. The hydrostatic pressure of the blood in the glomerular capillaires (Pg) is the main force for driving the fluid (Water and solute) out of the glomerulus.
The pressure is opposed by two forces:
(i) The hydrostatic pressure of the Bowman’s Capsule fluid (PBC).
(ii) The osmotic pressure of the plasma proteins (Ppp).
Therefore, the effective filtration pressure (Pef) is calculated by the following relation:
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Pef = Pg – (PPP + PBC)
... Pef = 74 – (30 + 20) mm of Hg
... Pef = 24 mm of Hg.
Thus, by substituting the normal values of the various forces, it has been found that the calculated effective (net) filtration pressure (Pef) is 24 mm Hg.
A fall in blood pressure may reduce the Pef which results in less amount of urine. When the aortic systolic pressure is reduced to 70 mm Hg, the hydrostatic pressure of the blood in glomerular capillaries is reduced to 50 mm. Hg. This reduces the Pef to Zero [50 – 50] and thus filtration will be ceased. Under such circumstances, urine will not be formed (anuria) until the blood pressure is maintained.
b. Tubular Reabsorption:
The rate of formation of the primary urine is 120 ml/minute, while the rate of urine passing to the bladder under the same condition is 1-2 ml/ minute. Therefore, it indicates that about 99 per cent of the glomerular filtrate is reabsorbed during its passage through the different segments of the renal tubule.
Although, the glomerular filtrate contains nearly the same concentration of glucose as in plasma, the urine contains nil or very little glucose. Hence, glucose is also practically completely reabsorbed in the tubules when the blood sugar level is normal. The capacity of reabsorption depends on the renal threshold of that substance.
The reabsorption of different solids takes place at different sites in the renal tubules. Amino acids, glucose, and small amounts of protein that pass through the glomerulus are reabsorbed in the first part of the proximal tubule.
Sodium, chloride, and bicarbonate are reabsorbed uniformly along the entire length of the proximal tubule and also in the distal tubule. Potassium is reabsorbed in the proximal and secreted in the distal tubule.
The glomerular filtrate produces about 170 litres in a day; whereas the tubules reabsorb about 168.5 litres of water, 170 gm of glucose, 100 gm of NaCl, 360 gm of NaHCO3, and small amounts of phosphate, sulphate, amino acids, urea, uric acid, etc. and excrete about 60 gm of NaCl, urea and other waste products in about 1.5 litres of urine. Most of these solids are reabsorbed by active transport mechanism, while some (e.g., urea) are reabsorbed by passive transport mechanism.
In diseases, the reabsorption mechanism is altered developing glycosuria, phosphaturia, and amino aciduria.
c. Tubular Secretion:
Although, most of the substances are reabsorbed by the tubular cells, some substances are actively transported or actively excreted into the tubular lumen. The secreted substance by the tubular epithelium in man are creatinine and potassium. The tubular epithelium also removes a number of foreign substances that are introduced into the body for therapeutic and diagnostic purposes.
These foreign substances are penicillin, p-Aminosalicylic acid, phenosulphonphthalein (PSP), p-Aminohippuric acid, and diodrast. The hydrogen ions and ammonia formed in the distal tubular cells are also actively excreted into tubular lumen and thus pass to urine.
Hormonal regulation:
The function of kidney is regulated by three important hormones. These hormones are aldosterone (from adrenal cortex), parathormone (from parathyroid), and vasopressin (from hypophyseal posterior lobe).
Aldosterone restricts the excretion of Na+ and stimulates the excretion of K+. Parathormone stimulates excretion of phosphate. Vasopressin, the antidiuretic hormone, is held responsible mainly for the reabsorption of water. In the absence of this hormone, a large amount of very dilute urine is excreted.
Essay # 4. Mechanism of Action of Diuretics:
a. Diuretics, the drugs, enhance losses of water and salt via the urine through interference with normal reabsorptive mechanisms.
b. Osmotic diuretics are nonreabsorbable substances which increase tubular osmolarity. The osmotic substances which limit the amount of water. Osmotic diuresis is responsible for the serious dehydration which accompanies diabetic ketoacidosis.
c. Diamox is the inhibitor of carbonic anhydrase. It blocks both HCO3− reabsorption in the proximal tubule and regeneration in the distal tubule.
d. Thiazide diuretics, furosemide, ethacrynic acid and mercurials all inhibit chloride reabsorption in the ascending limb.
Essay # 5. Renal Function Tests:
Clearance is measured to assess quantitatively the rate of excretion of a given substance by the kidney. This is a volume of blood or plasma which contains the amount of the substance which is excreted in the urine in one minute.
A. Inulin Clearance:
a. Inulin is a polysaccharide which is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Therefore, it is a measure of glomerular filtration rate. Mannitol can also be used for the same purpose.
b. These clearances vary with the body size. The clearance is calculated on the basis of ml/1.73 m2.
c. To measure inulin clearance it is wise to maintain a constant plasma level of the test substance during the period of urine collections.
The clearance is measured according to the following formula:
Cin = U x V/P
where Cin = Clearance of inulin (ml/min)
U = Urinary inulin (mg/100 ml)
V = Volume of urine (ml/min)
P = Plasma inulin (mg/100 ml)
B. Endogenous Creatinine Clearance:
a. Creatinine is filtered at the glomerulus but not secreted or reabsorbed by the tubule. Its clearance is measured to get the GFR.
b. This method is convenient for the estimation of the GFR because it does not require the intravenous administration of a test substance.
c. Normal values for creatinine clearance are in males: 130 ± 20 ml/mt and females: 120 ± 15 ml/mt.
C. The Phenolsulphonephthalein (PSP) Test:
a. The dye is almost completely eliminated within 2 hours.
b. If less than 25 per cent of the dye is not excreted in 15 minutes, it is an indication of impairment of renal function.
D. Other Functional Tests:
a. Dilution test (water excretion test)
b. Urine concentration test (specific gravity test)
c. Vasopressin (ADH) test
d. Urine acidification test
e. Blood NPN, urea and creatinine
f. Urea clearance test.
a. Dilution test:
(i) After emptying the bladder of the individual after overnight fast, he is advised to drink 1200 ml water in 30 minutes.
(ii) During four hours after drinking, the urine is collected at hourly intervals.
(iii) In normal individuals in cold climates, 1200 ml of urine is excreted in four hours.
(iv) This test is not applicable to warm climates since the greater part of the ingested water is lost in perspiration during summer.
(v) In case of impaired renal function, the amount of water eliminated in four hours will be less than 1200 ml depending on the degree of impairment and specific gravity of urine is often 1.010 or higher in conditions of oliguria.
b. Urine concentration test (specific gravity test):
(i) The bladder is emptied on the day of the test at 7 a.m. and the urine is discarded.
(ii) The urine is collected at 8 a.m. and the specific gravity is measured. If the sp. gr. is 1.022, the test may be rejected.
(iii) If the sp. gr, is below 1.022, another urine specimen should be collected at 9 a.m. and the sp. gr. is determined.
(iv) In case, the urine does not have a sp. gr. of 1.022, it is sure that the renal concentrating power is impaired either due to tubular defects or decreased secretion of ADH (diabetes insipidus). If the urine volume is large and the sp. gr. is below 1.022, the ADH test must be carried out. 3.
c. Vasopressin (ADH) test:
(i) The individual is not allowed any food or water after 6 p.m. on the night before the test. Vasopressin (5 units) is injected intramuscularly at 7 p.m. in the night.
(ii) The urine is collected at 7 a.m. and 8 a.m. and the sp. gr. is determined. If the sp. gr. is 1.022, it is quite confident that the individual suffers from diabetes insipidus and ADH injection is effective in controlling it.
d. Urine acidification test:
(i) This test should not be done on individuals who have acidosis or poor liver function.
(ii) No dietary or other restrictions are involved in carrying out this test. The bladder is emptied at 8 a.m. Thereafter, hourly specimens of urine are collected until 6 p.m. At 10 a.m., ammonium chloride in a dose of 0.1 gram/kg body weight is given. A portion of each specimen is transferred to stoppered bottles and sent immediately to the laboratory for pH determination.
(iii) In normal individuals, all urine specimens collected after 2 hours from the time of administration of ammonium chloride should have a pH between 4.6 and 5.0 but in patients with renal tubular acidosis, the pH does not fall below 5.3.
v. Blood non-protein nitrogen:
(i) In acute nephritis, the NPN values are increased and range from a slight increase (NPN-45 mg, urea N-25 mg, creatinine-2 mg per 100 ml) to very high values (NPN- 200 mg, urea N-160 mg creatinine-25 mg per 100 ml).
(ii) NPN increase and retention are due to impaired renal function and excessive protein catabolism.
Essay # 6. Congenital Tubular Function Defects in Kidney:
a. Diabetes Insipidus:
(i) This disease is developed due to the non- production of ADHr. The individual passes large volume of urine (5-20 litres in 24 hours). The individual has to drink large amount of water to make up the loss.
(ii) The reabsorption of water in the distal tubules does not take place in the absence of ADH.
b. Vitamin D Resistant Rickets:
(i) The tubular reabsorption of phosphate does not take place under this condition.
(ii) Excessive loss of phosphate in urine leads to the development of a type of rickets which does not respond to usual doses of Vitamin D.
c. Renal Glycosuria:
In this condition, the tubular reabsorption of glucose is affected. Although the blood sugar is within normal level but glucose is excreted in urine due to defective reabsorption by the tubules.
d. Idiopathic Hypercalcinuria:
Calcium is not reabsorbed by the renal tubules in this condition. Hence, large amounts of calcium are excreted in the urine. Renal calculi may be developed owing to the presence of large amounts of calcium in urine.
e. Salt losing Nephritis:
(i) Large amounts of sodium and chloride ions are excreted in urine in this condition due to the defect in the tubular reabsorption of these ions resulting in severe dehydration, hyponatremia and hypo-chloremia.
(ii) Blood urea is increased due to the reduced glomerular filtration rate.
(iii) This condition does not respond to aldosterone administration but responds to parenteral administration of sodium chloride solution.
f. Renal Tubular Acidosis:
(i) In this condition, the urine becomes alkaline or neutral due to the defect in the sodium and hydrogen ion exchange mechanism in the distal tubules. There is a loss of sodium in the urine.
(ii) The acidosis is accompanied by excessive mobilization and urinary excretion of calcium and potassium.
(iii) These abnormalities led to clinical manifestation of dehydration, hypokalemia, defective mineralisation of bones and nephrocalcinosis.
g. Fanconi Syndrome:
(i) A number of defects in tubular reabsorption exist in this condition. The defects are renal amino acid in renal glycosuria, hyperphosphaturia, metabolic aciduria, with increased urinary excretion of Na, Ca and K.
(ii) In some individuals, cystinosis prevails due to the abnormality of cystine metabolism in which cystine crystals are deposited in macrophages in the liver, kidney, spleen, bone marrow, lymph nodes and cornea.
h. Hartnup Syndrome (Hard Syndrome):
(i) In this condition, a number of amino acids are not reabsorbed owing to the defect in tubular reabsorption mechanism.
(ii) Disturbances in tryptophan metabolism is suggested by the presence of increased amounts of tryptophan, indican and indole acetic acid in urine.
(iii) The clinical symptoms are of niacin deficiency—a pellagra like skin lesions and mental deficiency.
i. Nephrogenic Diabetes Insipidus (Water-Losing Nephritis):
This condition is due to congenital defect in water reabsorption in the distal tubules and may, therefore, resemble true diabetes insipidus.
Essay # 7. Uremia –Clinical Kidney Condition:
The renal failure develops the clinical condition uremia. This condition occurs both in the chronic renal failure and acute failure. The concentration of urea and other NPN constituents in plasma are increased depending on the severity of this condition.
In chronic renal disease, excretion of acid (hydrogen ion) and also of phosphate ion is impaired. This results in the steady development of acidosis in uremia.
In acute renal failure, the urine output is very low (300 ml or less in 24 hours). This leads to a steady increase in urea and NPN constituents and electrolytes (K+ and Na+) in plasma. There is rapid development of acidosis too.
The important findings of severe chronic uremia or acute uremia are:
a. High concentration of urea and other NPN constituents.
b. High serum potassium concentration.
c. – Water retention leading to generalised edema.
d. Acidosis.
Uremic coma occurs in serious cases:
i. Urea and NPN:
The concentration of urea and other NPN constituents of blood are very much increased (i.e., 10 times the normal level) in severe renal failure.
ii. Potassium:
The potassium ion level may be slightly increased in chronic uremia. But in acute uremia, the concentration in serum is very much increased. Potassium is released from the cells due to the breakdown of cellular proteins. This released potassium passes into the blood and interstitial fluid.
When the concentration of potassium ion increases to 8 m. Eq/litre, it exerts a cardiotoxic effect resulting in the dilatation of the heart and when potassium ion concentration reaches at 12 to 15 mEq/ litre, the heart is likely to be stopped. This happens in severe uremia.
iii. Water Retention and Edema:
If the uremic patient drinks water and consumes other fluids, the water is retained in the body. If salt is not consumed, water retention increases in both the intracellular and extracellular fluid resulting in extracellular edema.
iv. Acidosis:
The metabolic processes in the body produce daily 50 to 100 m mol of more metabolic acid than alkali. This extra metabolic acid is excreted mainly through the kidneys. Acidosis develops rapidly in acute uremia. The patient faces ‘Coma’ due to severe acidosis.
Essay # 8. The Artificial Kidney:
During recent years, the artificial kidney has been developed to such an extent that several thousand patients with permanent renal insufficiency or even total kidney removal are being maintained in health for years.
The artificial kidney passes blood through very minute channels bounded by thin membranes. There is a dialyzing fluid on the other side of the membrane into which unwanted substances present in the blood pass by diffusion. The blood is pumped continually between two thin sheets of cellophane; the dialyzing fluid is on the outside of the sheets.
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The cellophane is porous enough to allow all constituents of the plasma except the plasma proteins to diffuse freely in both directions—from plasma into the dialyzing fluid and from the dialyzing fluid into the plasma.
The rate of flow of blood through the artificial kidney is several hundred ml per minute. Heparin is infused into the blood as it enters the kidney to prevent clotting of blood. To prevent bleeding as a result of heparin, an anti-heparin substance, such as protamine, is infused into the blood as it is returned to the patient.
The Dialyzing Fluid:
Sodium, potassium and chloride concentrations in the dialyzing fluid and in normal plasma are identical; but in uremic plasma, the potassium and chloride concentrations are considerably greater. These two ions diffuse through the dialyzing membrane so rapidly that their concentrations fall to equal those in the dialyzing fluid within three to four hours, exposure to the dialyzing fluid.
On the other hand, there is no phosphate, urea, urate or creatinine in the dialyzing fluid.
When the uremic patient is dialyzed, these substances are lost in large quantities into the dialyzing fluid, thereby removing major proportions of them from the plasma. Thus, the constituents of the dialyzing fluid are such that those substances in excess in the extracellular fluid in uremia be removed at rapid rates, while the essential electrolytes remain quite normal.
Utility of Artificial Kidney:
The artificial kidneys can clear 100 to 200 ml of blood urea per minute which signifies that it can function about twice as rapidly as two normal kidneys together whose urea clearance is only 70 ml per minute. However, the artificial kidney can be used for not more than 12 hours once in three to four days because of danger from excess heparin and infection to the subject.
Essay # 9. Hormones of the Kidney:
a. Not only the kidney performs excretory functions but it acts as an endocrine organ. It liberates many hormones which affect other organs and tissues and some hormones which locally act within the kidney itself. It also destroys several hormones which are liberated from other endocrine organs.
b. The juxtaglomerular cells of the renal cortex produce the proteolytic enzyme rennin and secrete it into the blood. Rennin acts on a2-globulin which is normally present in blood plasma, although it is produced in the liver.
Rennin splits off a polypeptide fragment called angiotensin I which is decapeptide containing 10 amino acids. Another enzyme of the lung acts on angiotensin I to split off 2 amino acids and thus form the octapeptide angiotensin II.
Angiotensin increases the force of the heartbeat and constricts the arterioles. It raises blood pressure and causes contraction of smooth muscle. It is destroyed by the enzyme angiotensinases present in normal kidneys, plasma and other tissues. Recent studies suggest that rennin angiotensin system is important in the maintenance of normal blood pressure.
c. Prostaglandins are the other hormones of the kidney. They cause relaxation of smooth muscles. They cause vasodilatation and a decrease in blood pressure. They also increase renal blood flow. Kininogen which is produced by the kidney has an antihypertensive effect.
d. The two hormones erythropoietin and erythrogenin have an effect on bone marrow to stimulate production of red cells. Kidney plays an important role in the release of erythropoietin and thus in control of red cell production. Hypoxia stimulates production of erythropoietin.
