PHYSIOLOGY OF RENAL SYSTEM

URINE FORMATION

Kidneys excrete the unwanted substances including metabolic end products and those substances, which are present in excess quantities in the body, through urine. Normally, about 1 to 1.5 liters of urine is formed everyday. The mechanism of urine formation includes various processes.

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The urine formation includes three processes: I. Glomerular filtration II. Tubular reabsorption III. Tubular secretion.

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GLOMERULAR FILTRATION RATE (GFR) Glomerular filtration rate (GFR) is the total quantity of filtrate formed in all the nephrons of both the kidneys in the given unit of time. The normal GFR is 125 ml per minute or about 180 liters per day.

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MECHANISM OF REABSORPTION

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The basic transport mechanisms involved in tubular reabsorption are of two types; Active reabsorption Passive reabsorption

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Active Reabsorption. Active reasbsorption is the movement of molecules against the electrochemical (up hill) gradient. It needs liberation of energy which is derived from ATP. The substances reabsorbed actively from the renal tubule are sodium, calcium, potassium, phosphates, sulfates, bicarbonates, glucose, amino acids, ascorbic acid, uric acid and ketone bodies

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Passive Reabsorption In this, the molecules move along the electrochemical (down hill) gradient. This process does not need energy. The substances reabsorbed by passive transport area chloride, urea and water.

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SITE OF REABSORPTION
Substances Reabsorbed from proximal convoluted Tubule Glucose, amino acids, sodium, potassium, calcium, bicarbonates, chlorides, phosphates, uric acid and water are reabsorbed from proximal convoluted tubule. Substances Reabsorbed from Loop of Henle The substances reabsorbed from loop of Henle are sodium and chloride. Substances Reabsorbed from Distal Convolued Tubule Sodium, bicarbonate and water are reabsorbed from www.similima.com 8 distal convoluted tubule.

REABSORPTION OF IMPORTANT SUBSTANCES Reabsorption of Sodium
Sodium reabsorption occurs in three steps:

Transport from lumen of renal tubules into the tubular epithelial cells. Transport from tubular cells into the interstitial fluid Transport from interstitial fluid to the blood.

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Reabsorption of Glucose

Glucose is completely reabsorbed in the proximal convoluted tubule. It is transported by sodium co-transport mechamism. Glucose and sodium bind to a common carrier protein in the luminal membrane of tubular epithelium and enter the cell. The carrier protein is called sodium-dependant glucose transporter 2 (SGLT2). From tubular cell glucose is transported into medulalry interstitium by another carrier protein called glucose transporter 2 (Glutwww.similima.com 2) 10

Reabsorption of Amino Acids

Amino acids are also reabsorbed completely in proximal convoluted tubule. Amino acids are reabsorbed actively by the secondary active transport mechanism along with sodium.

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Reabsorpion of Bicarbonates

Bicarbonate is mostly present as sodium bicarbonate in the filtrate. Sodium bicarbonate dissociates into sodium and bicarbonate ions in the tubular lumen. Sodium diffuses into tubular cell in exchange of hydrogen. Bicarbonate combines with hydrogen to form carbonic acid. Carbonic acid dissociates into carbon dioxide and water in the presence of carbonic anhydrase. Carbon dioxide and water enter the tubular cell. www.similima.com 12

Hormone

Action

Aldosterone Increases sodium reabsorpion in ascending limb, distal convoluted tubule and collecting duct. Angiotension II Increases sodium reabsorption in proximal tubule, thick ascending limb, distal tubule and collecting duct (mainly in proximal convoluted tubule)Antidiuretic hormone Increases water reabsorpion in distal convoluted tubule and collecting ductAtrial natriuretic factor Decreases sodium reabsorptionBrain natriuretic factor Decreases sodium reabsorptionParathormone Increases reabsorpion of calcium, magnesium and Hydrogen. Decreases phosphate reabsorpionCalcitonin Decreases calcium reabsorpion
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In the tubular cells, carbon dioxide combines with water to form carbonic acid. It immediately dissociates into hydrogen and bicarbonate. Bicarbonate from the tubular cell enters the interstitium. There it combines with sodium to form sodium bicarbonate.

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Tm Value

for every actively reabsorbed substance, there is a maximum rate at which it could be reabsorbed. The maximum rate at which a substance is reabsorbed from the renal tubule is called tubular transport maximum or Tm. For example, the transport maximum for glucose (TmG) is 380 mg/minute.

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TUBULAR SECRETION

In addition to reabsorption from renal tubules, some substances are also secreted into the lumen from the peritubular capillaries through the tubular epithelial cells. It is known as tubular secretion or tubular excretion

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Thus, urine, is formed in the nephron by the processes of glomerular filtration, selective reabsoption and tubular secrtion.

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CONCENTRATION OF URINE

Osmolarity of glomerular filtrate is same as that of plasma and it is 300 mOsm/L. But, normally urine is concentrated and is osmolarity is four times more than that of plasma, i.e. 1200 mOsm/L. Osmalarity of urine depends upon two factors:
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Water content in the body Antidiuretic hornone.
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FORMATION OF DILUTE URINE

When the water content in body increases, kidney excretes dilute urine. It is achieved by the inhibition of ADH secretion

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FORMATION OF CONCENTRATED URINE

WHEN THE WATER CONTENT IN THE BODY DECREASES, KIDNEY EXCRETES CONCENTRATED URINE IT INVOLVES TWO IMPORTANT PROCESSES 1. Medullary gradient which is developed and maintained by counter current system 2. Secretion of ADH
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MEDULLARY GRADIENT MEDULLARY HYPEROSMOLARITY The osmolarity of the interstitial fluid in the renal cortex is similar to that of plasma and it is 300mOsm/ L. The osmolarity of the interstitial fluid in the renal medulla near the cortex also is 300 mOsm/L.But in the inner part of the medulla it reaches maximum.This type of gradual increase in the osmolarity is called medullary gradient.
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DEVELOPMENT AND MAINTENANCE OF MEDULLARY GRADIENT Kidneys unique anatomical arrangements called countercurrent system is responsible for this.

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COUNTERCURRENT MECHANISM COUNTERCURRENT FLOW In kidney,the structures,that forms the countercurrent systems are the loop of Henle and the vasa recta.In both ,the direction of flow of fluid in the descending limb is just opposite to that in in the ascending limb.The loop of Henle forms the countercurrent multiplier and the vasa recta forms the countercurrent exchanger.
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ROLE OF ADH The final concentration of urine is achieved by ADH. Normally, the distal convoluted tubule and the collecting duct are not permeable to water. In the presence of ADH, they become permeable to water resulting in water reabsorption. The water reabsorption induced by ADH is called facultative reabsorption of water. A large quantity of water is removed from the fluid while passing through distal convoluted tubule and collecting duct. So, the urine becomes hypertonic with an osmolarity of 1200mOsm/L.

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APPLIED PHYSIOLOGY
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Kidneys fail to concentrate or dilute the urine in some pathological conditions Osmotic Diuresis – Generally, loss of large quantity of water through rine is called diuresis. Excretion of large amont of water through urine due to the osmotic effects of solutes like glucose is called osmotic diuresis. It is common in diabetes mellitus. Polyuria – Increased urinary output with increased frequency of voiding is called polyuria. It is common in diabetes insipidus. In this disorder the renal tubules fail to reabsorb because of ADH deficiency

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Syndrome of Inappropriate Hypersecretion of ADH – It is a pituitary disorder characterised by hypersecretion of ADH. Excess ADH causes water retension which decreases osmolarity of ECF. Nephrogenic Diabetes Insipidus – Sometimes, ADH secretion is normal but the renal tubules fail to give response to ADH resulting in polyria. This condition is called nephrogenic diabetes insipidus. BARTTER’S SYNDROME – It is a genetic disorder characterised by defect in the thick ascending segment resulting in loss of sodium and water through urine.

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ACIDIFICATION OF URINE AND ROLE OF KIDNEY IN ACID BASE BALANCE

kidney plays an important role in maintenanace of acid base balance by excreting hydrogen ions and retaining bicarbonate ions. Normally, urine is acidic in naure with a pH of 4.5 to 6. the metabolic activities in the body produce lots of acids which threaten to push the body towards acidosis. But kidneys prevent this by excreting hydrogen ions and conserving bicarbonate ions.
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SECRETION OF HYDROGEN IONS

Secretion of H+ into the renal tubules occurs by the formation of carbonic acid. CO2 formed in the tubular cells combines with water to form carbonic acid. CO2 enters the cells from tubular fluid also. Carbonic anhydrase is essential for the formation of carbonic acid. This enzyme is available in large quantities in epithelial cells of the renal tubules. The carbonic acid immediately dissociates into H+ and HCO3-. There are two mechanisms for the secretion of H+. Sodium-Hydrogen antiport pump ATP driven proton pump
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REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF URINE BICARBONATE MECHANISMS All the filtered HCO3- into the renal tubules is reabsorbed. The reabsorption of HCO3- utilises the H+ present in renal tubules. The H+ secreted into the renal tubule, combines with filtered HCO3- forming carbonic acid. Carbonic acid dissociates into CO2 and H2O in the presence of carbonic anhydrase. Both enters the tubular cell. In the tubular cell CO2 combines with water to form carbonic acid.
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It immediately dissociates into H+ andHCO3-. HCO3- from the tubular cell enters the interstitium. There it combines with Na+ to form NaHCO3. now, the H+ is secreted into the tubular lumen from the cell in exchange for Na+. thus for every H+ secreted into lumen of tubule, oneHCO3- is reabsorbed from the tubule. In this way kidneys conserve the HCO3-. The reabsorption of filtered HCO3- is an important factor in maintaining pH of the body fluids
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PHOSPHATE MECHANISMS

In the tubular cells CO2 combines with water to form carbonic acid. It immediately dissociates into H+ and HCO3-. HCO3- from the tubular cells enters the interstitium. Simultaneously, Na+ is reabsorbed from renal tubule under the influence of aldosterone. Na+ eners the interstitium and combines with HCO3-

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The H+ is secreted into tubular lumen from the cell in exchange for Na+. the H+ which is secreted into the renal tubules, reacts with phosphate buffer system. It combines with sodium hydrogen phosphate to form sodium dihydrogen phosphate. This is excreted in urine. The H+ which is added to urine in the form of dihydrogen makes the urine acidic.it occurs in distal tubule and collecting duct.
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AMMONIA MECHANISMS

This is the most important mechanisms by which kidneys excrete H+ and make the urine acidic. In the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into glutamic acid in the presence of the enzyme glutaminase. Ammonia is also formed by the deamination of some of the amino acids such as glycine and alanine. The ammonia formed in tubular cells is secreted into tubular lumen in exchange for sodium ion. Here it combines with H+ to form ammonium
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The tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and combines with sodium acetoacetate to form ammonium acetoacetate. It is excreted through urine. Thus, H+ is added to urine in the form of ammonium compounds resulting in acidification of urine. This occurs mostly in the proximal convoluted tubule because glutamine is converted into ammonia in the cells of this segment. Thus by excreting H+ and conserving HCO3-, kidneys produce acidic urine and help to maintain the acid base balance of body fluis.

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APPLIED PHYSIOLOGY

In renal disease, kidney fails to excrete metabolic acids resulting in metabolic acidosis. When kidney excretes large number of H+, metabolic alkalosis occurs

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