physiology renal system

PHYSIOLOGY OF PHYSIOLOGY OF RENAL SYSTEMRENAL SYSTEM

URINE FORMATIONURINE FORMATION Kidneys excrete the unwanted substances Kidneys excrete the unwanted substances

including metabolic end products and those including metabolic end products and those substances, which are present in excess substances, which are present in excess quantities in the body, through urine. quantities in the body, through urine.

Normally, about 1 to 1.5 liters of urine is Normally, about 1 to 1.5 liters of urine is formed everyday. The mechanism of urine formed everyday. The mechanism of urine formation includes various processes.formation includes various processes.

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


GLOMERULAR FILTRATION RATE GLOMERULAR FILTRATION RATE (GFR)(GFR)

Glomerular filtration rate (GFR) is the total Glomerular filtration rate (GFR) is the total quantity of filtrate formed in all the nephrons quantity of filtrate formed in all the nephrons of both the kidneys in the given unit of time.of both the kidneys in the given unit of time.

The normal GFR is 125 ml per minute or The normal GFR is 125 ml per minute or about 180 liters per day. about 180 liters per day.


MECHANISM OF MECHANISM OF REABSORPTIONREABSORPTION

The basic transport mechanisms involved in The basic transport mechanisms involved in

tubular reabsorption are of two types; tubular reabsorption are of two types; Active reabsorptionActive reabsorption Passive reabsorptionPassive reabsorption


Active Reabsorption.Active Reabsorption. Active reasbsorption is the movement of molecules Active reasbsorption is the movement of molecules

against the electrochemical (up hill) gradient. It against the electrochemical (up hill) gradient. It needs liberation of energy which is derived from needs liberation of energy which is derived from ATP.ATP.

The substances reabsorbed actively from the renal The substances reabsorbed actively from the renal tubule are sodium, calcium, potassium, phosphates, tubule are sodium, calcium, potassium, phosphates, sulfates, bicarbonates, glucose, amino acids, sulfates, bicarbonates, glucose, amino acids, ascorbic acid, uric acid and ketone bodiesascorbic acid, uric acid and ketone bodies


Passive ReabsorptionPassive Reabsorption In this, the molecules move along the In this, the molecules move along the

electrochemical (down hill) gradient. This electrochemical (down hill) gradient. This process does not need energy.process does not need energy.

The substances reabsorbed by passive The substances reabsorbed by passive transport area chloride, urea and water.transport area chloride, urea and water.


SITE OF REABSORPTIONSITE OF REABSORPTIONSubstances Reabsorbed from proximal convoluted Substances Reabsorbed from proximal convoluted

TubuleTubule Glucose, amino acids, sodium, potassium, calcium, Glucose, amino acids, sodium, potassium, calcium,

bicarbonates, chlorides, phosphates, uric acid and bicarbonates, chlorides, phosphates, uric acid and water are reabsorbed from proximal convoluted water are reabsorbed from proximal convoluted tubule.tubule.

Substances Reabsorbed from Loop of HenleSubstances Reabsorbed from Loop of Henle The substances reabsorbed from loop of Henle are The substances reabsorbed from loop of Henle are

sodium and chloride. sodium and chloride. Substances Reabsorbed from Distal Convolued TubuleSubstances Reabsorbed from Distal Convolued Tubule Sodium, bicarbonate and water are reabsorbed from Sodium, bicarbonate and water are reabsorbed from

distal convoluted tubule.distal convoluted tubule. 88www.similima.comwww.similima.com

REABSORPTION OF IMPORTANT REABSORPTION OF IMPORTANT SUBSTANCES SUBSTANCES

Reabsorption of SodiumReabsorption 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 fluidTransport from interstitial fluid to the blood.


Reabsorption of GlucoseReabsorption of Glucose Glucose is completely reabsorbed in the Glucose is completely reabsorbed in the

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


Reabsorption of Amino AcidsReabsorption of Amino Acids

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


Reabsorpion of BicarbonatesReabsorpion of Bicarbonates

Bicarbonate is mostly present as sodium Bicarbonate is mostly present as sodium bicarbonate in the filtrate. Sodium bicarbonate bicarbonate in the filtrate. Sodium bicarbonate dissociates into sodium and bicarbonate ions in dissociates into sodium and bicarbonate ions in the tubular lumen. Sodium diffuses into the tubular lumen. Sodium diffuses into tubular cell in exchange of hydrogen. tubular cell in exchange of hydrogen. Bicarbonate combines with hydrogen to form Bicarbonate combines with hydrogen to form carbonic acid. Carbonic acid dissociates into carbonic acid. Carbonic acid dissociates into carbon dioxide and water in the presence of carbon dioxide and water in the presence of carbonic anhydrase. Carbon dioxide and water carbonic anhydrase. Carbon dioxide and water enter the tubular cell.enter the tubular cell. 1212www.similima.comwww.similima.com

Hormone Hormone ActionAction AldosteroneAldosterone Increases sodium reabsorpion in ascending Increases sodium reabsorpion in ascending

limb, distal convoluted tubule and limb, distal convoluted tubule and collecting duct. Angiotension IIcollecting duct. Angiotension II Increases sodium Increases sodium reabsorption in proximal tubule, thick reabsorption in proximal tubule, thick ascending limb, distal tubule and collecting duct (mainly ascending limb, distal tubule and collecting duct (mainly in proximal convoluted in proximal convoluted tubule)Antidiuretic hormonetubule)Antidiuretic hormone Increases water reabsorpion Increases water reabsorpion in distal convoluted tubule and in distal convoluted tubule and collecting ductAtrial natriuretic factor collecting ductAtrial natriuretic factor Decreases sodium Decreases sodium reabsorptionBrain natriuretic factorreabsorptionBrain natriuretic factor Decreases sodium Decreases sodium reabsorptionParathormonereabsorptionParathormone Increases reabsorpion of Increases reabsorpion of calcium, magnesium and calcium, magnesium and Hydrogen. Decreases phosphate reabsorpionCalcitonin Hydrogen. Decreases phosphate reabsorpionCalcitonin

Decreases calcium reabsorpion Decreases calcium reabsorpion


In the tubular cells, carbon dioxide combines In the tubular cells, carbon dioxide combines with water to form carbonic acid. It with water to form carbonic acid. It immediately dissociates into hydrogen and immediately dissociates into hydrogen and bicarbonate. Bicarbonate from the tubular cell bicarbonate. Bicarbonate from the tubular cell enters the interstitium. There it combines with enters the interstitium. There it combines with sodium to form sodium bicarbonate.sodium to form sodium bicarbonate.


Tm ValueTm Value for every actively reabsorbed substance, there for every actively reabsorbed substance, there

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


TUBULAR SECRETIONTUBULAR SECRETION

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


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


CONCENTRATION OF URINECONCENTRATION OF URINE Osmolarity of glomerular filtrate is same as Osmolarity of glomerular filtrate is same as

that of plasma and it is 300 mOsm/L. But, that of plasma and it is 300 mOsm/L. But, normally urine is concentrated and is normally urine is concentrated and is osmolarity is four times more than that of osmolarity is four times more than that of plasma, i.e. 1200 mOsm/L. Osmalarity of plasma, i.e. 1200 mOsm/L. Osmalarity of urine depends upon two factors:urine depends upon two factors: Water content in the bodyWater content in the body Antidiuretic hornone.Antidiuretic hornone.


FORMATION OF DILUTE URINEFORMATION OF DILUTE URINE

When the water content in body When the water content in body increases, kidney excretes dilute increases, kidney excretes dilute urine.urine.

It is achieved by the inhibition of It is achieved by the inhibition of ADH secretionADH secretion


FORMATION OF FORMATION OF CONCENTRATED URINECONCENTRATED URINE

WHEN THE WATER CONTENT IN THE WHEN THE WATER CONTENT IN THE BODY DECREASES, KIDNEY EXCRETES BODY DECREASES, KIDNEY EXCRETES CONCENTRATED URINECONCENTRATED URINE

IT INVOLVES TWO IMPORTANT IT INVOLVES TWO IMPORTANT PROCESSES PROCESSES

1. Medullary gradient which is developed and 1. Medullary gradient which is developed and maintained by counter current systemmaintained by counter current system

2. Secretion of ADH2. Secretion of ADH


MEDULLARY GRADIENTMEDULLARY GRADIENT MEDULLARY HYPEROSMOLARITYMEDULLARY HYPEROSMOLARITY The osmolarity of the interstitial fluid in the renal The osmolarity of the interstitial fluid in the renal

cortex is similar to that of plasma and it is 300mOsm/cortex is similar to that of plasma and it is 300mOsm/L.L.

The osmolarity of the interstitial fluid in the renal The osmolarity of the interstitial fluid in the renal medulla near the cortex also is 300 mOsm/L.But in medulla near the cortex also is 300 mOsm/L.But in the inner part of the medulla it reaches the inner part of the medulla it reaches maximum.This type of gradual increase in the maximum.This type of gradual increase in the osmolarity is called medullary gradient.osmolarity is called medullary gradient.


DEVELOPMENT AND MAINTENANCE OF DEVELOPMENT AND MAINTENANCE OF MEDULLARY GRADIENTMEDULLARY GRADIENT

Kidneys unique anatomical arrangements Kidneys unique anatomical arrangements called countercurrent system is responsible for called countercurrent system is responsible for this.this.


COUNTERCURRENT MECHANISMCOUNTERCURRENT MECHANISM COUNTERCURRENT FLOWCOUNTERCURRENT FLOW In kidney,the structures,that forms the countercurrent In kidney,the structures,that forms the countercurrent

systems are the loop of Henle and the vasa recta.In systems are the loop of Henle and the vasa recta.In both ,the direction of flow of fluid in the descending both ,the direction of flow of fluid in the descending limb is just opposite to that in in the ascending limb is just opposite to that in in the ascending limb.The loop of Henle forms the countercurrent limb.The loop of Henle forms the countercurrent multiplier and the vasa recta forms the countercurrent multiplier and the vasa recta forms the countercurrent exchanger.exchanger.


ROLE OF ADHROLE OF ADH The final concentration of urine is achieved by ADH. The final concentration of urine is achieved by ADH.

Normally, the distal convoluted tubule and the collecting duct Normally, the distal convoluted tubule and the collecting duct are not permeable to water. In the presence of ADH, they are not permeable to water. In the presence of ADH, they become permeable to water resulting in water reabsorption. become permeable to water resulting in water reabsorption. The water reabsorption induced by ADH is called facultative The water reabsorption induced by ADH is called facultative reabsorption of water. reabsorption of water.

A large quantity of water is removed from the fluid while A large quantity of water is removed from the fluid while passing through distal convoluted tubule and collecting duct. passing through distal convoluted tubule and collecting duct. So, the urine becomes hypertonic with an osmolarity of So, the urine becomes hypertonic with an osmolarity of 1200mOsm/L.1200mOsm/L.


APPLIED PHYSIOLOGYAPPLIED PHYSIOLOGY Kidneys fail to concentrate or dilute the urine in some Kidneys fail to concentrate or dilute the urine in some

pathological conditionspathological conditions Osmotic Diuresis – Generally, loss of large quantity of water Osmotic Diuresis – Generally, loss of large quantity of water

through rine is called diuresis. Excretion of large amont of through rine is called diuresis. Excretion of large amont of water through urine due to the osmotic effects of solutes like water through urine due to the osmotic effects of solutes like glucose is called osmotic diuresis. It is common in diabetes glucose is called osmotic diuresis. It is common in diabetes mellitus.mellitus.

Polyuria – Increased urinary output with increased frequency Polyuria – Increased urinary output with increased frequency of voiding is called polyuria. It is common in diabetes of voiding is called polyuria. It is common in diabetes insipidus. In this disorder the renal tubules fail to reabsorb insipidus. In this disorder the renal tubules fail to reabsorb because of ADH deficiencybecause of ADH deficiency


Syndrome of Inappropriate Hypersecretion of ADH – It is a Syndrome of Inappropriate Hypersecretion of ADH – It is a pituitary disorder characterised by hypersecretion of ADH. pituitary disorder characterised by hypersecretion of ADH. Excess ADH causes water retension which decreases Excess ADH causes water retension which decreases osmolarity of ECF.osmolarity of ECF.

Nephrogenic Diabetes Insipidus – Sometimes, ADH Nephrogenic Diabetes Insipidus – Sometimes, ADH secretion is normal but the renal tubules fail to give response secretion is normal but the renal tubules fail to give response to ADH resulting in polyria. This condition is called to ADH resulting in polyria. This condition is called nephrogenic diabetes insipidus.nephrogenic diabetes insipidus.

BARTTER’S SYNDROME – It is a genetic disorder BARTTER’S SYNDROME – It is a genetic disorder characterised by defect in the thick ascending segment characterised by defect in the thick ascending segment resulting in loss of sodium and water through urine.resulting in loss of sodium and water through urine.


ACIDIFICATION OF URINE AND ROLE ACIDIFICATION OF URINE AND ROLE OF KIDNEY IN ACID BASE BALANCEOF KIDNEY IN ACID BASE BALANCE

kidney plays an important role in maintenanace of kidney plays an important role in maintenanace of acid base balance by excreting hydrogen ions and acid base balance by excreting hydrogen ions and retaining bicarbonate ions. retaining bicarbonate ions.

Normally, urine is acidic in naure with a pH of 4.5 to Normally, urine is acidic in naure with a pH of 4.5 to 6.6.

the metabolic activities in the body produce lots of the metabolic activities in the body produce lots of acids which threaten to push the body towards acids which threaten to push the body towards acidosis.acidosis.

But kidneys prevent this by excreting hydrogen ions But kidneys prevent this by excreting hydrogen ions and conserving bicarbonate ions. and conserving bicarbonate ions.


SECRETION OF HYDROGEN IONSSECRETION OF HYDROGEN IONS

Secretion of H+ into the renal tubules occurs by the formation Secretion of H+ into the renal tubules occurs by the formation of carbonic acid. CO2 formed in the tubular cells combines of carbonic acid. CO2 formed in the tubular cells combines with water to form carbonic acid. CO2 enters the cells from with water to form carbonic acid. CO2 enters the cells from tubular fluid also. Carbonic anhydrase is essential for the tubular fluid also. Carbonic anhydrase is essential for the formation of carbonic acid. This enzyme is available in large formation of carbonic acid. This enzyme is available in large quantities in epithelial cells of the renal tubules. The carbonic quantities in epithelial cells of the renal tubules. The carbonic acid immediately dissociates into H+ and HCO3-. acid immediately dissociates into H+ and HCO3-.

There are two mechanisms for the secretion of H+. There are two mechanisms for the secretion of H+.

Sodium-Hydrogen antiport pumpSodium-Hydrogen antiport pump

ATP driven proton pumpATP driven proton pump2828www.similima.comwww.similima.com

REMOVAL OF HYDROGEN IONS AND REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF URINEACIDIFICATION OF URINE

BICARBONATE MECHANISMSBICARBONATE MECHANISMS All the filtered HCO3- into the renal tubules is All the filtered HCO3- into the renal tubules is

reabsorbed. The reabsorption of HCO3- utilises the reabsorbed. The reabsorption of HCO3- utilises the H+ present in renal tubules. The H+ secreted into the H+ present in renal tubules. The H+ secreted into the renal tubule, combines with filtered HCO3- forming renal tubule, combines with filtered HCO3- forming carbonic acid. Carbonic acid dissociates into CO2 and carbonic acid. Carbonic acid dissociates into CO2 and H2O in the presence of carbonic anhydrase. Both H2O in the presence of carbonic anhydrase. Both enters the tubular cell. In the tubular cell CO2 enters the tubular cell. In the tubular cell CO2 combines with water to form carbonic acid. combines with water to form carbonic acid.


It immediately dissociates into H+ andHCO3-. It immediately dissociates into H+ andHCO3-. HCO3- from the tubular cell enters the interstitium. HCO3- from the tubular cell enters the interstitium. There it combines with Na+ to form NaHCO3. now, There it combines with Na+ to form NaHCO3. now, the H+ is secreted into the tubular lumen from the cell the H+ is secreted into the tubular lumen from the cell in exchange for Na+. thus for every H+ secreted into in exchange for Na+. thus for every H+ secreted into lumen of tubule, oneHCO3- is reabsorbed from the lumen of tubule, oneHCO3- is reabsorbed from the tubule. In this way kidneys conserve the HCO3-. The tubule. In this way kidneys conserve the HCO3-. The reabsorption of filtered HCO3- is an important factor reabsorption of filtered HCO3- is an important factor in maintaining pH of the body fluidsin maintaining pH of the body fluids


PHOSPHATE MECHANISMSPHOSPHATE MECHANISMS

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


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


AMMONIA MECHANISMSAMMONIA MECHANISMS

This is the most important mechanisms by which This is the most important mechanisms by which kidneys excrete H+ and make the urine acidic. In kidneys excrete H+ and make the urine acidic. In the tubular epithelial cells, ammonia is formed the tubular epithelial cells, ammonia is formed when the amino acid glutamine is converted into when the amino acid glutamine is converted into glutamic acid in the presence of the enzyme glutamic acid in the presence of the enzyme glutaminase. Ammonia is also formed by the glutaminase. Ammonia is also formed by the deamination of some of the amino acids such as deamination of some of the amino acids such as glycine and alanine. The ammonia formed in glycine and alanine. The ammonia formed in tubular cells is secreted into tubular lumen in tubular cells is secreted into tubular lumen in exchange for sodium ion. Here it combines with H+ exchange for sodium ion. Here it combines with H+ to form ammoniumto form ammonium


The tubular cell membrane is not permeable to The tubular cell membrane is not permeable to ammonium. Therefore, it remains in the lumen and ammonium. Therefore, it remains in the lumen and combines with sodium acetoacetate to form combines with sodium acetoacetate to form ammonium acetoacetate. It is excreted through urine. ammonium acetoacetate. It is excreted through urine. Thus, H+ is added to urine in the form of ammonium Thus, H+ is added to urine in the form of ammonium compounds resulting in acidification of urine. This compounds resulting in acidification of urine. This occurs mostly in the proximal convoluted tubule occurs mostly in the proximal convoluted tubule because glutamine is converted into ammonia in the because glutamine is converted into ammonia in the cells of this segment. Thus by excreting H+ and cells of this segment. Thus by excreting H+ and conserving HCO3-, kidneys produce acidic urine and conserving HCO3-, kidneys produce acidic urine and help to maintain the acid base balance of body fluis.help to maintain the acid base balance of body fluis.


APPLIED PHYSIOLOGYAPPLIED PHYSIOLOGY

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


physiology renal system

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acid base balance

proximal convoluted tubule

distal convoluted tubule

glomerular filtration rate

carbonic acid dissociates

form carbonic acid

tubular epithelial cells

renal tubules fail