Functions of the kidneys Functions of the kidneys A. Main functionA. Main function::regulation of volume & composition of regulation of volume & composition of body fluids, done by :body fluids, done by :-- Filtration of plasma at the glomeruli Filtration of plasma at the glomeruli

at rate of 120 ml/minute (170 L/day)at rate of 120 ml/minute (170 L/day)GFR.GFR.

-- Absorption of selected amounts of Absorption of selected amounts of water, electrolytes, glucose and water, electrolytes, glucose and

amino acids. Also secretion of amino acids. Also secretion of certain certain substances.substances.-- Excretion of urine with waste Excretion of urine with waste products (1 - 1.5 liters/day)products (1 - 1.5 liters/day)

Functions of the kidneysFunctions of the kidneysB. Endocrine (hormonal) function:B. Endocrine (hormonal) function:1. Production of:1. Production of: i. Renin: i. Renin:

From juxtglomerular Apparatus From juxtglomerular Apparatus Generates Angiotensin II.Generates Angiotensin II. ii. Erythropoietin: ii. Erythropoietin:

From interstitial Peritubular cells From interstitial Peritubular cells

Stimulate RBCs formation.Stimulate RBCs formation.2. 2. Vitamin D metabolism hydroxylation Vitamin D metabolism hydroxylation of 25-hydroxycholecalciferol intoof 25-hydroxycholecalciferol into1,25-dihydroxycholecalciferol1,25-dihydroxycholecalciferol"Active form of Vitamin D.”"Active form of Vitamin D.”

Function of the kidneyFunction of the kidneyThe basic functional unit is the nephron.The basic functional unit is the nephron.Each kidney contains ~10Each kidney contains ~1066 nephrons. nephrons.The kidneys receive 20-25% of the cardiac output.The kidneys receive 20-25% of the cardiac output.Glomerular filtration rate depends on filtration Glomerular filtration rate depends on filtration pressure at the glomerulus which is regulated by:pressure at the glomerulus which is regulated by:A- Efferent arteriole constriction by A- Efferent arteriole constriction by angiotensin II.angiotensin II.B- Afferent arteriole dilatation by B- Afferent arteriole dilatation by Prostaglandin.Prostaglandin.C- Mechanical “autoregulation”.C- Mechanical “autoregulation”.The epithelial cells are not dividing cells.The epithelial cells are not dividing cells.The filtration barrier allows water, electrolytes, The filtration barrier allows water, electrolytes, glucose, amino acids to pass.glucose, amino acids to pass.*Proteins below MW 20’000 can freely pass.*Proteins below MW 20’000 can freely pass.*Proteins above MW 65’000 can NOT pass through *Proteins above MW 65’000 can NOT pass through the barrier.the barrier.

- Afferent arteriole = Pre-glomerular- Afferent arteriole = Pre-glomerular- Efferent arteriole = Post-glomerular- Efferent arteriole = Post-glomerular

Disorders of urine volumeDisorders of urine volume Normally urine volume/24 hours Normally urine volume/24 hours ~~ 1-1.5 liter 1-1.5 liter Anuria (no urine excretion) is due to either: Anuria (no urine excretion) is due to either:

a. Total urinary obstruction.a. Total urinary obstruction.b. Vascular occlusion. b. Vascular occlusion.

Oliguria - urine output / 24 hours is below 500 ml. Oliguria - urine output / 24 hours is below 500 ml. Polyuria - urine output / 24 hours is above 3 liters. Polyuria - urine output / 24 hours is above 3 liters.

Causes:Causes:1. Excess fluid intake.1. Excess fluid intake.2. Hyperglycemia. 2. Hyperglycemia. 3. Diabetes inspidus3. Diabetes inspidus(decreased or absence of (decreased or absence of antidiuretic hormone)antidiuretic hormone)4. Drugs 4. Drugs diuretics diuretics Toxins Toxins lithium lithium

HaematuriaHaematuria Means urine contains blood or RBCs.Means urine contains blood or RBCs.CausesCauses -Bleeding from anywhere in renal tract:-Bleeding from anywhere in renal tract:

A. Kidneys:A. Kidneys:i. Clotting disordersi. Clotting disordersii. Cystii. Cystiii. Tumoriii. Tumoriv. Glumerular diseaseiv. Glumerular diseasev. Interstitial diseasev. Interstitial diseasevi. Infarctionvi. Infarction

B. Ureter:B. Ureter:i. Canceri. Cancerii. Stoneii. Stone

C. Urinary Bladder:C. Urinary Bladder:InfectionInfection

D. Urethra:D. Urethra:Trauma in urethra.Trauma in urethra.

HaematuriaHaematuriaHaematuria:Haematuria:

a. Frank Bleedinga. Frank Bleedingb. Microscopical bleedingb. Microscopical bleeding“RBCs detected in urine by microscope”“RBCs detected in urine by microscope”Normally:Normally:Few RBCs are detected by microscope.Few RBCs are detected by microscope. ** Dipstick test can detect Dipstick test can detect microscopical bleeding.microscopical bleeding.** +ve Dipstick test is positive during +ve Dipstick test is positive during menstruationmenstruation..Examination of urine is helpful in Examination of urine is helpful in establishing the cause of hematuria:establishing the cause of hematuria:1.1. Presence of WBCs and micro-Presence of WBCs and micro-organisms organisms suggests infection. suggests infection. 2.2. Presence of RBC casts suggests Presence of RBC casts suggests glomerular bleeding.glomerular bleeding.

HaematuriaHaematuriaGlomerular bleeding suggests fracture Glomerular bleeding suggests fracture in the glomerular basement membrane in the glomerular basement membrane (GBM).(GBM).

Glomerular bleeding may develop after Glomerular bleeding may develop after strenuous exercise.strenuous exercise.

Recurrent episodes of gross Recurrent episodes of gross haematuria associated with respiratory haematuria associated with respiratory tract infection indicates IgA tract infection indicates IgA nephropathy:nephropathy:

Glomerulonephrits with deposition of Glomerulonephrits with deposition of IgA in mesangial cells.IgA in mesangial cells.

HaematuriaHaematuriaRed urine due to haematuria must be Red urine due to haematuria must be differentiated from other causes of red or black differentiated from other causes of red or black urine:urine: 1. Hemoglobinuria: red urine 1. Hemoglobinuria: red urine

Myoglobinuria: very dark or black urineMyoglobinuria: very dark or black urine

*Both show positive dipstick test but no*Both show positive dipstick test but no RBCs on microscopy. RBCs on microscopy.

2. Food dye 2. Food dye beetroot beetroot 3. Porphyria 3. Porphyria urine darkens on standing urine darkens on standing4. ALKAPTONURIA 4. ALKAPTONURIA Dark brown or Dark brown or dark dark urineurine5. Drugs :5. Drugs :* Senna (orange urine)* Senna (orange urine)* Rifampicin (orange urine)* Rifampicin (orange urine)* L. Dopa (the urine darkens on standing)* L. Dopa (the urine darkens on standing)

ProteinuriaProteinuria Presence of abnormal concentration of proteins in Presence of abnormal concentration of proteins in the urine .the urine .*Proteinuria makes urine froth easily!*Proteinuria makes urine froth easily!

1. Low molecular weight Proteins:1. Low molecular weight Proteins: ** Normally low MW proteins are filtered at Normally low MW proteins are filtered at glomeruli, but are absorbed by tubular cellsglomeruli, but are absorbed by tubular cells** Less than 150 mg/day should appear in the Less than 150 mg/day should appear in the urine urine ** Appearance of more than 150mg of low MW Appearance of more than 150mg of low MW

proteins in the urine 24 hours means failure of proteins in the urine 24 hours means failure of reabsorption by tubular cells and indicates reabsorption by tubular cells and indicates

tubular cell damage.tubular cell damage.** Proteinuria of low MW proteins more than Proteinuria of low MW proteins more than 2g/day 2g/day indicates significant glomerular indicates significant glomerular disease.disease.

ProteinuriaProteinuria2. Albuminuria2. Albuminuria

** Normally albumin is not filtered at Normally albumin is not filtered at glomeruli.glomeruli.

** Presence of albumin in the urine is a Presence of albumin in the urine is a positive sign of positive sign of glomerular diseaseglomerular disease. .

-- Albuminuria is seen in early stages Albuminuria is seen in early stages of of glomerular disease of diabetes glomerular disease of diabetes

mellitus mellitus "diabetic nephropathy"diabetic nephropathy“.“.

** Minor leakage of albumin into Minor leakage of albumin into glomerular filtrate may occur glomerular filtrate may occur temporarily temporarily after after vigorousvigorous exercise, exercise, fever and heart fever and heart disease. disease.

Abnormal proteins in the urineAbnormal proteins in the urineIn myeloma (malignant proliferation of In myeloma (malignant proliferation of plasma cells) immunoglobulin light plasma cells) immunoglobulin light chains (MW chains (MW ~~ 25 KDa) appear in the 25 KDa) appear in the urine. This is called “Bence Jones urine. This is called “Bence Jones proteinuria” . proteinuria” . This proteinuria is poorly detected by This proteinuria is poorly detected by dipstick test and needs special dipstick test and needs special procedure. procedure. The protein precipitates when urine is The protein precipitates when urine is heated to 60heated to 60oo , and disappears when , and disappears when urine is boiled and reappears when the urine is boiled and reappears when the urine coolsurine cools..

NEPHROTIC SYNDROMENEPHROTIC SYNDROME

Is due to loss large quantities of protein in the urine. Is due to loss large quantities of protein in the urine. The signs and symptoms start to appear when proteinuria is The signs and symptoms start to appear when proteinuria is about 3.5 grams/day. about 3.5 grams/day. Characteristics of nephrotic syndrome:Characteristics of nephrotic syndrome:1.1. Serum albumin is less than 3 grams/100 ml.Serum albumin is less than 3 grams/100 ml.2.2. Signs of fluid retention or edema.Signs of fluid retention or edema.3.3. Proteinuria of more than 3.5 g/24 hours. Proteinuria of more than 3.5 g/24 hours. Causes of nephrotic syndrome: Causes of nephrotic syndrome: The diseases causing nephrotic syndrome always affect the The diseases causing nephrotic syndrome always affect the glomeruli.glomeruli.1. Glomerulonephritis. 1. Glomerulonephritis. 2. Systemic diseases: 2. Systemic diseases:

"Diabetic nephropathy, amyloidosis""Diabetic nephropathy, amyloidosis"

Clinical features of nephrotic syndromeClinical features of nephrotic syndrome1.1. EdemaEdema

** Is due to hypoalbuminemia and NaIs due to hypoalbuminemia and Na++ retention. retention. ** Starts in lower limbs and extending to genitalia and Starts in lower limbs and extending to genitalia and lower lower abdomen (in severe case).abdomen (in severe case).-- Ascites occurs early in children Ascites occurs early in children ** In the morning the edema is seen in upper limbs and In the morning the edema is seen in upper limbs and face. face.

2.2. Hypercoagulability Hypercoagulability ** tendency for clot tendency for clot formation .formation .** Is due to loss of anticoagulants.Is due to loss of anticoagulants.** It may lead to venous thrombosis and emboli formation. It may lead to venous thrombosis and emboli formation.

3.3. Infection Infection ** Is due to hypogammaglobulinemia Is due to hypogammaglobulinemia

4.4. Hypercholesterolemia Hypercholesterolemia ** Leads to arterial occlusion Leads to arterial occlusion (Enzymes involved in cholesterol metabolism are lost in urine).(Enzymes involved in cholesterol metabolism are lost in urine).

GlomerulonephritisGlomerulonephritis (GN) (GN)Inflammation of glomeruli Inflammation of glomeruli It is mostly It is mostly immunologicallyimmunologically mediated mediated evidence for this:evidence for this:1.1. Deposition of anti-glomerular basement Deposition of anti-glomerular basement

membrane antibodies membrane antibodies 2.2. Response of several types of GN to Response of several types of GN to immunosuppresive drugs.immunosuppresive drugs.** The antibody - Antigen complexes The antibody - Antigen complexes are are

deposited in the glomeruli.deposited in the glomeruli.These complexes are formed from These complexes are formed from

reaction of the antibodies against reaction of the antibodies against glomerular antigens or with antigens glomerular antigens or with antigens deposited in the glomeruli.deposited in the glomeruli.

GlomerulonephritisGlomerulonephritis (GN) (GN)

Acute post - infection glomerulonephritis Acute post - infection glomerulonephritis *Mostly seen after streptococcal infection*Mostly seen after streptococcal infection

Signs and symptoms:Signs and symptoms:-- NaNa++ retention retention -- EdemaEdema-- Hypertension Hypertension -- Proteinuria Proteinuria -- Hematuria Hematuria -- Reduced renal volumeReduced renal volume

Acute tubular necrosis (ATN)Acute tubular necrosis (ATN)

** Necrosis of cells of kidney tubules. Necrosis of cells of kidney tubules. ** It is the most common cause of acute renal It is the most common cause of acute renal

failure.failure.• Tubular cell death is Caused by:Tubular cell death is Caused by:

aa. Reduce renal blood flow. Reduce renal blood flowb. Toxinsb. Toxins

i. Chemical “Drugs”:i. Chemical “Drugs”:- Gentamycin- Gentamycin- Cytotoxic drugs- Cytotoxic drugs- Amphotericin B- Amphotericin B

ii. Bacterial Toxinsii. Bacterial Toxins

Acute tubular necrosis (ATN)Acute tubular necrosis (ATN)Reduce blood flow to tubular cells leads to less OReduce blood flow to tubular cells leads to less O22 delivery to tubular cells specially to cells of thick delivery to tubular cells specially to cells of thick ascending loop of Henleascending loop of Henle(they are very active metabolically) (they are very active metabolically) Death of the cells Death of the cells Shedding of the cells into the Shedding of the cells into the lumen of the tubules leading to occlusion .lumen of the tubules leading to occlusion .

Also reduction in OAlso reduction in O22 delivery to tubular cells leads to delivery to tubular cells leads to breaks in tubular basement membrane causing breaks in tubular basement membrane causing leakage of tubular content into interstitial tissues of leakage of tubular content into interstitial tissues of the kidney.the kidney.Note:Note:Tubular cells can regenerate function. Tubular cells can regenerate function. *In ATN there is period of diuresis*In ATN there is period of diuresis( ( Increased urine output).Increased urine output).This is due to loss of concentration gradient of This is due to loss of concentration gradient of kidney medullakidney medulla..

Renal failureRenal failure Failure of kidneys functions.Failure of kidneys functions.

Primarily failure of excretory function Primarily failure of excretory function Leads to retention of nitrogenous Leads to retention of nitrogenous waste waste products that produced by products that produced by body body metabolism.metabolism.

Also other functions of the kidneys may Also other functions of the kidneys may Fail:Fail:1. Regulation of fluid and electrolytes 1. Regulation of fluid and electrolytes balance balance

2. Regulation of acid - base balance 2. Regulation of acid - base balance

3. Endocrine function3. Endocrine function

Renal failure is either Acute renal failure Renal failure is either Acute renal failure (ARF) (ARF) Or chronic renal failure (CRF) Or chronic renal failure (CRF)

Acute renal failureAcute renal failure

Sudden entire or almost entire loss of kidneys Sudden entire or almost entire loss of kidneys function which develops over a period of function which develops over a period of days or days or weeks. weeks. ** A plasma creatinine concentration of A plasma creatinine concentration of more more than than 200 µmol/liter is used as a 200 µmol/liter is used as a biochemical biochemical definition of ARF.definition of ARF.Also KAlso K++ and urea concentrations in the blood are and urea concentrations in the blood are also increased in acute renal failure. also increased in acute renal failure. ** Normal creatinine level is Normal creatinine level is between 55-120 between 55-120 µmol/Lµmol/L** Normal urea Normal urea concentration 2.5-6.5 mmol/L.concentration 2.5-6.5 mmol/L.

[K+] = 3.5-5 mmol/L[K+] = 3.5-5 mmol/L

Acute renal failureAcute renal failureARF is usually reversibleARF is usually reversible(the renal function usually returns)(the renal function usually returns)

If renal function is not restored rapidly If renal function is not restored rapidly in ARF, a temporary renal replacement in ARF, a temporary renal replacement therapy may be required.therapy may be required.

Causes of ARF:Causes of ARF:1. Pre - renal 1. Pre - renal

2. Intrinsic renal disease 2. Intrinsic renal disease

3. Post - renal3. Post - renal

acute renal failure:acute renal failure: Causes ofCauses of

Acute renal failureAcute renal failure1. Pre - renal causes of ARF:1. Pre - renal causes of ARF:

Result in a decrease in renal blood flow.Result in a decrease in renal blood flow.

Causes: Causes:

1. Systemic Causes1. Systemic Causes

*Circulatory shock due to hemorrhage *Circulatory shock due to hemorrhage or or excessive water loss as vomiting, excessive water loss as vomiting, diarrhea and burns.diarrhea and burns.

*Heart failure *Heart failure

2. Local causes like renal artery stenosis, 2. Local causes like renal artery stenosis, renal artery occlusion and disease affecting renal artery occlusion and disease affecting renal arterioles.renal arterioles.

Acute renal failureAcute renal failure2. Intrinsic renal causes2. Intrinsic renal causes(abnormalities within the kidney itself):(abnormalities within the kidney itself):

could lead to ARF, these include:could lead to ARF, these include:

diseases affecting→ Glomeruli diseases affecting→ Glomeruli

→ → Blood vesselsBlood vessels

→ → Renal tubulesRenal tubules

Acute renal failureAcute renal failure*Acute glomerulonephritis:*Acute glomerulonephritis:This is caused by immune reactions that damage This is caused by immune reactions that damage glomeruli.glomeruli.It develops after streptococcal infection else where in the It develops after streptococcal infection else where in the body (for ex. Tonsillitis or sore throat). body (for ex. Tonsillitis or sore throat).

Antibodies against streptococcal antigensAntibodies against streptococcal antigens ↓ ↓Formation of antibodies-antigens complexFormation of antibodies-antigens complex ↓ ↓Depositions of these complexes in glomeruliDepositions of these complexes in glomeruli ↓ ↓Destruction of the glomeruli from these immune Destruction of the glomeruli from these immune

reactions. reactions.Another mechanism for development of Another mechanism for development of glomerulonephritis is the reaction of certain antibodies glomerulonephritis is the reaction of certain antibodies with glomerular antigens. This reaction causes damage with glomerular antigens. This reaction causes damage of the glomeruli leading to ARF.of the glomeruli leading to ARF.

Acute renal failureAcute renal failure*Diseases affecting tubules (85% of ARF due to *Diseases affecting tubules (85% of ARF due to intrinsic renal diseases are of this type)intrinsic renal diseases are of this type)

→ → Either severe ischemia of renal tubulesEither severe ischemia of renal tubules

→ → Or toxic chemical substances and bacterial Or toxic chemical substances and bacterial toxins affecting tubulestoxins affecting tubules

↓ ↓ lead tolead to

Death of renal tubules epithelial cells Death of renal tubules epithelial cells ↓↓

Tubular cells slough off Tubular cells slough off

↓↓

blockage of renal tubulesblockage of renal tubules

Acute renal failureAcute renal failure3. Post-renal causes of ARF are due to 3. Post-renal causes of ARF are due to obstruction of renal flow. obstruction of renal flow. *Sites of obstruction:*Sites of obstruction:a. a. Bilateral obstruction of ureters or renal Bilateral obstruction of ureters or renal pelvices.pelvices.b. bladder obstructionb. bladder obstructionc. uretheral obstructionc. uretheral obstruction

*Causes of obstruction could be*Causes of obstruction could be1. stones 2. tumor 3. inflammation1. stones 2. tumor 3. inflammation→→ Obstruction of urine flow leads slowly Obstruction of urine flow leads slowly progressive destruction of renal tissues. Also progressive destruction of renal tissues. Also leads to infection which results in rapid leads to infection which results in rapid decrease in renal function.decrease in renal function.

Reversible pre-renal ARFReversible pre-renal ARFCauses → Systemic (shock, hypotension)Causes → Systemic (shock, hypotension)

This may be due to blood loss or loss of intravascular This may be due to blood loss or loss of intravascular fluid into tissues as in cases of burns, crush injuries, fluid into tissues as in cases of burns, crush injuries, sepsis →sepsis →Local ( renal artery stenosis or occlusionLocal ( renal artery stenosis or occlusion

and renal arteriols abnormalities)and renal arteriols abnormalities)

** Renal blood flow is ≈1200 ml/min. This highRenal blood flow is ≈1200 ml/min. This high

blood flow is essential to keep high GFR blood flow is essential to keep high GFR (120ml/min).(120ml/min).

*High GFR is needed for effective regulation of body *High GFR is needed for effective regulation of body water and electrolytes. A decrease in blood flow leads to water and electrolytes. A decrease in blood flow leads to a decrease in GFR and thus decreasing the ability of the a decrease in GFR and thus decreasing the ability of the kidneys to excrete excess water and electrolytes kidneys to excrete excess water and electrolytes

Reversible pre-renal ARFReversible pre-renal ARF** Normally the kidneys can regulate their blood flow and Normally the kidneys can regulate their blood flow and

GFR over wide range variation in blood pressure.GFR over wide range variation in blood pressure.The mechanisms of this regulation are:The mechanisms of this regulation are:a. Vasodilatation of afferent arteriols through liberationa. Vasodilatation of afferent arteriols through liberation

of prostaglandins.of prostaglandins.b. A decrease in stretching of renal blood vessels b. A decrease in stretching of renal blood vessels

(in case of a decrease in BP) leads to vasodilatation.(in case of a decrease in BP) leads to vasodilatation.This is called auto-regulation of renal blood flow.This is called auto-regulation of renal blood flow.

c. A vasoconstriction of efferent arteriols by c. A vasoconstriction of efferent arteriols by Angiotensin II:Angiotensin II:

This effect is mediated through the release of renin from This effect is mediated through the release of renin from juxtaglomerular apparatus.juxtaglomerular apparatus.When the above mechanisms fail to maintain blood When the above mechanisms fail to maintain blood Flow, then GFR decreased and this leads to formation Flow, then GFR decreased and this leads to formation of a low urine volume (oliguria).of a low urine volume (oliguria).

Established acute renal failure:Established acute renal failure:Causes : Causes :

1.1. prolonged kidneys under perfusion (i.e. prolonged prolonged kidneys under perfusion (i.e. prolonged ischemia of renal tubules which follows circulatory ischemia of renal tubules which follows circulatory shock). Because of high metabolic activity of tubular shock). Because of high metabolic activity of tubular cells, a decrease in blood flow reduces delivery of cells, a decrease in blood flow reduces delivery of oxygen to them and this causes acute tubular necrosis oxygen to them and this causes acute tubular necrosis and shedding of tubular cells into tubular lumens and shedding of tubular cells into tubular lumens obstructing them.obstructing them.

2.2. Toxic effects of drugs and chemicalsToxic effects of drugs and chemicals3.3. Conditions affecting intra-renal arteries and arteriolsConditions affecting intra-renal arteries and arteriols

like vasculitis, hypertension and disseminated like vasculitis, hypertension and disseminated intravascular coagulation.intravascular coagulation.

4.4. prolonged obstruction of urine flow.prolonged obstruction of urine flow.

Clinical features of established ARF:Clinical features of established ARF:The signs and symptoms are combination of The signs and symptoms are combination of underlying condition that caused the renal failure underlying condition that caused the renal failure and those of renal failure itself.and those of renal failure itself.

1. abnormalities of urine volume1. abnormalities of urine volume

*Oliguria*Oliguria

*Anuria→ it is rare and indicates acute urinary *Anuria→ it is rare and indicates acute urinary tract obstruction or vascular occlusion.tract obstruction or vascular occlusion.

*Sometimes urine volume is normal or increased *Sometimes urine volume is normal or increased (seen in 20% of patients). This is due to low (seen in 20% of patients). This is due to low GFR and poor tubular absorption and does not GFR and poor tubular absorption and does not mean normal kidney excretory function.mean normal kidney excretory function.

Clinical features of established ARF:Clinical features of established ARF:2. blood chemistry abnormalities2. blood chemistry abnormalities

* High plasma urea and creatinine concentrations. * High plasma urea and creatinine concentrations. The rate of the increase of these substances depends on The rate of the increase of these substances depends on catabolic state of the body.catabolic state of the body.for ex. If there is severe infection, trauma and surgery, for ex. If there is severe infection, trauma and surgery, then the rate of increase is high.then the rate of increase is high.* Hyperkalemia* Hyperkalemia is common specially if there massive is common specially if there massive break down of tissues, hemolysis and acidosis.break down of tissues, hemolysis and acidosis.*Hyperkalemia*Hyperkalemia must be corrected because of its effect must be corrected because of its effect on heart function (causes ventricular arrhythmia). on heart function (causes ventricular arrhythmia). *If plasma K*If plasma K++ concentration is more 7 mmol/l, cardiac concentration is more 7 mmol/l, cardiac arrest may occur.arrest may occur.*Dilutional hyponatremia (reduced plasma Na*Dilutional hyponatremia (reduced plasma Na++))occurs if water intake is free or inappropriate amount occurs if water intake is free or inappropriate amount of intravascular water is given.of intravascular water is given.

Clinical features of established ARF:Clinical features of established ARF:2. blood chemistry abnormalities (Cont.)2. blood chemistry abnormalities (Cont.)*Hypocalcaemia*Hypocalcaemia: is due to less: is due to less1,25-dihydroxycholicalciferol which is formed in the kidney.1,25-dihydroxycholicalciferol which is formed in the kidney.* Acid-base disturbances→ Metabolic acidosis.* Acid-base disturbances→ Metabolic acidosis.* Signs and symptoms of waste products retention. * Signs and symptoms of waste products retention. These include anorexia, vomiting, nausea, drowsiness, These include anorexia, vomiting, nausea, drowsiness, apathy, confusion, muscle twitching and coma.apathy, confusion, muscle twitching and coma.* Respiratory rate is increased (due to metabolic * Respiratory rate is increased (due to metabolic acidosis)acidosis)* Pulmonary edema may develop (due to retention of * Pulmonary edema may develop (due to retention of

fluid or inappropriate administration of excess fluid).fluid or inappropriate administration of excess fluid).* Anemia (due to blood loss and less erythropoietin * Anemia (due to blood loss and less erythropoietin

production).production).* Bleeding tendency* Bleeding tendency* Immunity depression and infection.* Immunity depression and infection.

Chronic Renal failure (CRF)Chronic Renal failure (CRF)An irreversible deterioration in renal function resulted An irreversible deterioration in renal function resulted from irreversible loss of large number of functioning from irreversible loss of large number of functioning nephrons. CRF occurs over a period of years.nephrons. CRF occurs over a period of years.In CR, there is loss of excretory, metabolic and In CR, there is loss of excretory, metabolic and endocrine functions of the kidney.endocrine functions of the kidney.The clinical signs and symptoms of CRF are sometimes The clinical signs and symptoms of CRF are sometimes referred to as referred to as UREMIA.UREMIA.Causes:Causes:Any factor or condition which destroys the normal Any factor or condition which destroys the normal function and structure of the kidneysfunction and structure of the kidneys(i.e. decreasing the no. of functional nephrons) may lead (i.e. decreasing the no. of functional nephrons) may lead to CRF. to CRF. In most cases, serious symptoms do not occur In most cases, serious symptoms do not occur until the no. functioning nephrons decreased below until the no. functioning nephrons decreased below 20-30% of normal20-30% of normal. .

Chronic Renal failure (CRF)Chronic Renal failure (CRF)Among conditions that lead to CRF are:Among conditions that lead to CRF are:

1. Metabolic disorders → Diabetes mellitus1. Metabolic disorders → Diabetes mellitus

2. Immunological disorder → glomerulonephritis2. Immunological disorder → glomerulonephritis

3. Renal vascular disorder → atherosclerosis3. Renal vascular disorder → atherosclerosis

4. primary tubular disorder → nephrotoxins like 4. primary tubular disorder → nephrotoxins like

analgesics and analgesics and heavy metal heavy metal

5. Infection → pyelonephritis5. Infection → pyelonephritis

6. Urinary tract obstruction6. Urinary tract obstruction

7. congenital disorders → polycystic kidneys7. congenital disorders → polycystic kidneys

8. Hypertension8. Hypertension

Clinical Features of CRFClinical Features of CRF**Early stageEarly stage: : CRF is often asymptomatic. Biochemical examination CRF is often asymptomatic. Biochemical examination shows an elevated blood urea and creatinine shows an elevated blood urea and creatinine concentration.concentration.Nocturia Nocturia may be an early symptom and it is due o loss may be an early symptom and it is due o loss of concentration ability of the kidneys.of concentration ability of the kidneys.**Sometimes, patient with CRF may present with **Sometimes, patient with CRF may present with complaints which are not renal in origin like complaints which are not renal in origin like breathlessness or tiredness.breathlessness or tiredness.* In late stage of CRF, the patient looks * In late stage of CRF, the patient looks ill, anemicill, anemic. The . The respiration is deep (Kussmaul’s breathing).respiration is deep (Kussmaul’s breathing).Anorexia, nausea, hiccough, pruritis, vomiting, Anorexia, nausea, hiccough, pruritis, vomiting, muscle twitching drowsiness and coma are among muscle twitching drowsiness and coma are among late signslate signs and symptoms of CRF. and symptoms of CRF.Actually, in late stage of CRF almost every body system Actually, in late stage of CRF almost every body system is affected.is affected.

Physical signs in CRFPhysical signs in CRF

Anemia of CRFAnemia of CRF: : This anemia may be caused by: This anemia may be caused by: 1. decrease in erythropoietin production1. decrease in erythropoietin production2. Inhibition in erythropoiesis by toxic effect of metabolic 2. Inhibition in erythropoiesis by toxic effect of metabolic

waste products on bone marrow.waste products on bone marrow.3. An increase in blood loss due to increased capillary 3. An increase in blood loss due to increased capillary

fragility and poor platelets function.fragility and poor platelets function.4. Reduction in dietary intake and absorption of iron and 4. Reduction in dietary intake and absorption of iron and

other substances needed for erythropoiesis.other substances needed for erythropoiesis.5. Shortening of RBC life span5. Shortening of RBC life span

*The severity of anemia in CRF is proportional to the *The severity of anemia in CRF is proportional to the severity of renal failure and anemia contributes to many severity of renal failure and anemia contributes to many non-specific symptoms of CRF.non-specific symptoms of CRF.

Bone abnormalities of CRF (Bone abnormalities of CRF (renal renal osteodystrophyosteodystrophy))

These abnormalities are mixture of:These abnormalities are mixture of:*Osteomalacia (failure of bone mineralization)*Osteomalacia (failure of bone mineralization)*Osteoporosis (reduction in bone mass)*Osteoporosis (reduction in bone mass)*Osteosclerosis (increased bone density)*Osteosclerosis (increased bone density)*In CRF there is less*In CRF there is less

1,25-dihydroxycholecalciferol(active form of vitamin D) 1,25-dihydroxycholecalciferol(active form of vitamin D) decrease absorption of Cadecrease absorption of Ca+2+2 from intestine from intestine hypocalcaemia, this causes:hypocalcaemia, this causes:A. Reduction in bone calcification.A. Reduction in bone calcification.B. Hyperparathyroidism B. Hyperparathyroidism Increased bone Increased bone

resorption resorption..* Excretion of phosphate is decreased in CRF leading * Excretion of phosphate is decreased in CRF leading

to to hyperphosphotaemiahyperphosphotaemia which stimulates the which stimulates the parathyroid glands.parathyroid glands.

* Osteoporosis of CRF is probably due to malnutrition.* Osteoporosis of CRF is probably due to malnutrition.

Chronic Renal FailureChronic Renal FailureMyopathy of CRFMyopathy of CRF

is due to a combination of poor nutrition, is due to a combination of poor nutrition,

hyperthyroidism, vitamin D deficiency and hyperthyroidism, vitamin D deficiency and electrolytes disturbances.electrolytes disturbances.

Neuropathy of CRFNeuropathy of CRF

Is due to demyelination of nerve fibers (the Is due to demyelination of nerve fibers (the longer fibers being involved at earlier stage).longer fibers being involved at earlier stage).

*parasthesia → sensory impairment*parasthesia → sensory impairment

*foot drop → motor neuropathy*foot drop → motor neuropathy

*delayed gastric*delayed gastric emptying}emptying}

diarrhea } diarrhea } Autonomic Autonomic

postural hypotension } neuropathypostural hypotension } neuropathy

Chronic Renal FailureChronic Renal FailureEndocrine disorders of CRFEndocrine disorders of CRF

HyperprolactinaemiaHyperprolactinaemia → causes a decrease in libido and → causes a decrease in libido and sexual function in ♀ and ♂sexual function in ♀ and ♂

HyperparathyroidismHyperparathyroidism → is due to hypocalcaemia and → is due to hypocalcaemia and hyperphosphotaemia hyperphosphotaemia

AmenorrheaAmenorrhea ( means absence of menstrual cycle in ♀) ( means absence of menstrual cycle in ♀)

There is also relative insulin resistance in CRF. There is also relative insulin resistance in CRF. However a decreased renal metabolism of insulin in However a decreased renal metabolism of insulin in CRF may reduce the daily requirements of insulin inCRF may reduce the daily requirements of insulin inDiabetics.Diabetics.

Chronic Renal FailureChronic Renal FailureMetabolic acidosisMetabolic acidosis

The increased HThe increased H++ leads to exchange of H leads to exchange of H++ instead of Cainstead of Ca2+2+ in the bone and this in the bone and this aggravating the metabolic disease of the aggravating the metabolic disease of the bone of CRF.bone of CRF.The respiration is strongly stimulated by The respiration is strongly stimulated by metabolic acidosis. The increased metabolic acidosis. The increased respiratory activity is an attempt to reduce respiratory activity is an attempt to reduce HH++ concentration by blowing of CO concentration by blowing of CO22. .

Plasma Plasma PPH less than 6.8 leads to coma H less than 6.8 leads to coma

and death.and death.

Chronic Renal FailureChronic Renal FailureCardiovascular disorder of CRF:Cardiovascular disorder of CRF:

80% of patients with CRF develop 80% of patients with CRF develop hypertensionhypertension. . The increase in BP is due to retention of NaThe increase in BP is due to retention of Na++ and and fluid. fluid. It is also due to production of renin,It is also due to production of renin,angiotensin II and aldosterone.angiotensin II and aldosterone.These hormones are increased in CRF specially These hormones are increased in CRF specially if there is under-perfusion of renal tissues due to if there is under-perfusion of renal tissues due to vascular diseases.vascular diseases.

* * AtherosclerosisAtherosclerosis is common and it is accelerated is common and it is accelerated by the hypertension.by the hypertension.

* * Vascular calcificationVascular calcification may also occur in CRF may also occur in CRF** Pericarditis Pericarditis is seen in end-stage renal failure. is seen in end-stage renal failure.

Chronic Renal FailureChronic Renal Failure

CRF and body fluidCRF and body fluidIf water and food are not restricted in complete CRF, the If water and food are not restricted in complete CRF, the following may occur:following may occur:

1. Generalized edema.1. Generalized edema.2. High urea and creatinine plasma 2. High urea and creatinine plasma

concentration. concentration. 3. High K3. High K++ and PO and PO44

3-3- plasma concentration. plasma concentration.4. Acidosis.4. Acidosis.5. Low HCO5. Low HCO33 plasma concentration. plasma concentration.

Infection and CRFInfection and CRFDue to decreased cellular and humoral immunity, the Due to decreased cellular and humoral immunity, the CRF patients are susceptible to infection. CRF patients are susceptible to infection.

Chronic Renal FailureChronic Renal FailureHypertension and CRFHypertension and CRF

* hypertension is seen in 80% of CRF patients. * hypertension is seen in 80% of CRF patients. When hypertension develops, it will increase the When hypertension develops, it will increase the severity of renal failure because hypertension severity of renal failure because hypertension causes further damage to glomeruli and renal causes further damage to glomeruli and renal blood vessels.blood vessels.*Conditions like renal artery stenosis reduce *Conditions like renal artery stenosis reduce renal blood flow and therefore reducing GFR renal blood flow and therefore reducing GFR and this leads to retention of water and and this leads to retention of water and development of hypertension.development of hypertension.*Chronic glomerulonephrirtis causes thickening *Chronic glomerulonephrirtis causes thickening of glomerular capillary membrane and therefore of glomerular capillary membrane and therefore decreasing GFR and subsequently development decreasing GFR and subsequently development of hypertension. of hypertension.

Chronic Renal FailureChronic Renal Failure

Hypertension and CRF (Cont.)Hypertension and CRF (Cont.)

* Conditions that increase * Conditions that increase aldosteronealdosterone secretion will lead to increased tubular Nasecretion will lead to increased tubular Na++ absorption which leads to water retention absorption which leads to water retention and subsequently development of and subsequently development of hypertension.hypertension.* Conditions that increase * Conditions that increase reninrenin secretion secretion leads to formation of angiotensin II, which leads to formation of angiotensin II, which causes retention of Nacauses retention of Na++ and water and and water and vasoconstriction and this will lead to vasoconstriction and this will lead to hypertension.hypertension.

Replacement of renal function in renal Replacement of renal function in renal failurefailure

**When kidneys stop working temporarily or permanently, **When kidneys stop working temporarily or permanently, metabolic waste products accumulate in the blood.metabolic waste products accumulate in the blood.It is essential to get rid of these toxic substances which It is essential to get rid of these toxic substances which worsen the condition and affect other body systems. It is worsen the condition and affect other body systems. It is also important to replace the endocrine function of the also important to replace the endocrine function of the failing kidneys.failing kidneys.

**It is possible to replace the excretory function of the **It is possible to replace the excretory function of the failed kidneys by failed kidneys by hemodialysis or peritoneal dialysishemodialysis or peritoneal dialysis..

**Dialysis is used to replace kidney function in acute **Dialysis is used to replace kidney function in acute renal function until the kidneys resume their function. renal function until the kidneys resume their function.

**In chronic renal failure, **In chronic renal failure, dialysis is used permanentlydialysis is used permanently until successful kidney transplant is done.until successful kidney transplant is done.

**Dialysis can not replace the endocrine and metabolic **Dialysis can not replace the endocrine and metabolic functions of the kidney. These function could be functions of the kidney. These function could be resumed by kidney transplant.resumed by kidney transplant.

Basic principle of dialysisBasic principle of dialysis

Please see Textbook of medical physiology Please see Textbook of medical physiology

by Guyton and Hall 10th edition page 378by Guyton and Hall 10th edition page 378