8-Renal Pa Tho Physiology (8)

8/2/2019 8-Renal Pa Tho Physiology (8)

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Functions of the kidneysFunctions of the kidneysA. 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 glomeruliFiltration 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 andwater, electrolytes, glucose and

amino acids. Also secretion of amino acids. Also secretion of certaincertain

substances.substances.

-- Excretion of urine with wasteExcretion 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 ApparatusFrom juxtglomerular Apparatus Generates Angiotensin II.Generates Angiotensin II.

ii. Erythropoietin:ii. Erythropoietin:From interstitial Peritubular cellsFrom interstitial Peritubular cells Stimulate RBCs formation.Stimulate RBCs formation.

2.2. Vitamin D metabolism hydroxylationVitamin D metabolism hydroxylationof 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 filtrationGlomerular filtration rate depends on filtrationpressure at the glomerulus which is regulated by:pressure at the glomerulus which is regulated by:A- Efferent arteriole constriction byA- Efferent arteriole constriction by angiotensin II.angiotensin II.B- Afferent arteriole dilatation byB- 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 the*Proteins above MW 65’000 can NOT pass through thebarrier.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 hoursNormally 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. Drugs4. Drugs diureticsdiuretics

ToxinsToxins lithiumlithium



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. Cyst

iii. Tumor iii. Tumor iv. Glumerular diseaseiv. Glumerular diseasev. Interstitial diseasev. Interstitial diseasevi. Infarctionvi. Infarction

B. Ureter:B. Ureter:

i. Cancer i. Cancer ii. 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 Bleeding

b. 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 detectDipstick test can detect microscopicalmicroscopicalbleeding.bleeding.** +ve Dipstick test is positive during+ve Dipstick test is positive duringmenstruationmenstruation..Examination of urine is helpful inExamination of urine is helpful inestablishing the cause of hematuria:establishing the cause of hematuria:1.1. Presence of WBCs and micro-organismsPresence of WBCs and micro-organisms

suggests infection.suggests infection.

2.2. Presence of RBC casts suggestsPresence of RBC casts suggests

glomerular bleeding.glomerular bleeding.



HaematuriaHaematuriaGlomerular bleeding suggests fractureGlomerular bleeding suggests fracture

in the glomerular basement membranein the glomerular basement membrane(GBM).(GBM).

Glomerular bleeding may develop after Glomerular bleeding may develop after

strenuous exercise.strenuous exercise.Recurrent episodes of grossRecurrent episodes of gross

haematuria associated with respiratoryhaematuria associated with respiratory

tract infection indicates IgAtract infection indicates IgAnephropathy:nephropathy:

Glomerulonephrits with deposition of Glomerulonephrits with deposition of

IgA in mesangial cells.IgA in mesangial cells.



HaematuriaHaematuriaRed urine due to haematuria must beRed urine due to haematuria must bedifferentiated from other causes of red or blackdifferentiated from other causes of red or black

urine:urine: 1. Hemoglobinuria: red urine1. Hemoglobinuria: red urineMyoglobinuria: 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 dye2. Food dye beetrootbeetroot

3. Porphyria3. Porphyria urine darkens on standingurine darkens on standing

4. ALKAPTONURIA4. ALKAPTONURIA Dark brown or darkDark brown or 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 thePresence of abnormal concentration of proteins in theurine .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 atNormally 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 urineLess than 150 mg/day should appear in the urine

** Appearance of more than 150mg of low MWAppearance of more than 150mg of low MWproteins in the urine 24 hours means failure of proteins in the urine 24 hours means failure of

reabsorption by tubular cells and indicatesreabsorption by tubular cells and indicatestubular cell damage.tubular cell damage.

** Proteinuria of low MW proteins more than 2g/dayProteinuria of low MW proteins more than 2g/dayindicates significant glomerular disease.indicates significant glomerular disease.



ProteinuriaProteinuria2. Albuminuria2. Albuminuria

** Normally albumin is not filtered atNormally albumin is not filtered atglomeruli.glomeruli.

** Presence of albumin in the urine is aPresence of albumin in the urine is a

positive sign of positive sign of glomerular diseaseglomerular disease..

-- Albuminuria is seen in early stagesAlbuminuria is seen in early stages of of

glomerular disease of diabetesglomerular disease of diabetes mellitusmellitus

"diabetic nephropathy"diabetic nephropathy“.“.

** Minor leakage of albumin intoMinor leakage of albumin intoglomerular filtrate may occur glomerular filtrate may occur temporarilytemporarily

after after vigorousvigorousexercise,exercise, fever and heartfever and heart

disease.disease.



proteinuriaproteinuria

Orthostatic proteinuria:Orthostatic proteinuria:

Proteinuria occurs only during the day.Proteinuria occurs only during the day.

First morning urine sample contains noFirst morning urine sample contains no

protein.protein.

Is usually benign in the absence of Is usually benign in the absence of

renal disease.renal disease.



Abnormal proteins in the urineAbnormal pr oteins in the urineIn myeloma (malignant proliferation of In myeloma (malignant proliferation of

plasma cells) immunoglobulin lightplasma cells) immunoglobulin lightchains (MWchains (MW ~~ 25 KDa) appear in the25 KDa) appear in theurine. This is called “Bence Jonesurine. This is called “Bence Jonesproteinuria” .proteinuria” .

This proteinuria is poorly detected byThis proteinuria is poorly detected bydipstick test and needs specialdipstick test and needs specialprocedure.procedure.

The protein precipitates when urine isThe protein precipitates when urine isheated to 60heated to 60oo , and disappears when, and disappears whenurine is boiled and reappears when theurine is boiled and reappears when theurine 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 isThe signs and symptoms start to appear when proteinuria isabout 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 theThe diseases causing nephrotic syndrome always affect theglomeruli.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 lower Starts in lower limbs and extending to genitalia and lower abdomen (in severe case).abdomen (in severe case).

-- Ascites occurs early in childrenAscites occurs early in children

** In the morning the edema is seen in upper limbs and face.In the morning the edema is seen in upper limbs and face.

2.2. HypercoagulabilityHypercoagulability

** tendency for clottendency 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. InfectionInfection

** Is due to hypogammaglobulinemiaIs due to hypogammaglobulinemia

4.4. HypercholesterolemiaHypercholesterolemia

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



GlomerulonephritisGlomerulonephr itis (GN)(GN)Inflammation of glomeruliInflammation of glomeruli

It is mostlyIt is mostly immunologicallyimmunologically mediatedmediatedevidence for this:evidence for this:

1.1. Deposition of anti-glomerular basementDeposition of anti-glomerular basementmembrane antibodiesmembrane antibodies

2.2. Response of several types of GN toResponse of several types of GN toimmunosuppresive drugs.immunosuppresive drugs.

** The antibody - Antigen complexesThe antibody - Antigen complexes arearedeposited in the glomeruli.deposited in the glomeruli.

These complexes are formed fromThese complexes are formed fromreaction of the antibodies againstreaction of the antibodies againstglomerular antigens or with antigensglomerular antigens or with antigensdeposited in the glomeruli.deposited in the glomeruli.



GlomerulonephritisGlomerulonephritis (GN)(GN)

Acute post - infection glomerulonephritisAcute post - infection glomerulonephritis

*Mostly seen after streptococcal infection*Mostly seen after streptococcal infection

Signs and symptoms:Signs and symptoms:-- NaNa++ retentionretention

-- EdemaEdema

-- HypertensionHypertension

-- ProteinuriaProteinuria-- HematuriaHematuria

-- 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 renalIt is the most common cause of acute renalfailure.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 drugsii. 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 O

22

delivery to tubular cells specially to cells of thickdelivery 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 cellsDeath of the cells Shedding of the cells into theShedding of the cells into thelumen 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 todelivery to tubular cells leads tobreaks in tubular basement membrane causingbreaks in tubular basement membrane causingleakage 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.



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

Primarily failure of excretory functionPrimarily failure of excretory function Leads to retention of nitrogenousLeads to retention of nitrogenous wastewaste

products that produced byproducts that produced by bodybody

metabolism.metabolism.

Also other functions of the kidneys mayAlso other functions of the kidneys may Fail:Fail:1. Regulation of fluid and electrolytes1. Regulation of fluid and electrolytes

balancebalance

2. Regulation of acid - base balance2. Regulation of acid - base balance3. Endocrine function3. Endocrine function

Renal failure is either Acute renal failureRenal 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 kidneysSudden entire or almost entire loss of kidneysfunction 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 thanmore than

200 µmol/liter is used as a200 µmol/liter is used as a biochemical definitionbiochemical definitionof ARF.of ARF.

Also KAlso K++ and urea concentrations in the blood are alsoand urea concentrations in the blood are alsoincreased in acute renal failure.increased in acute renal failure.

** Normal creatinine level isNormal creatinine level is between 55-120between 55-120µmol/Lµmol/L** Normal ureaNormal 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 rapidlyIf renal function is not restored rapidly

in ARF, a temporary renal replacementin ARF, a temporary renal replacement

therapy may be required.therapy may be required.Causes of ARF:Causes of ARF:

1. Pre - renal1. Pre - renal

2. Intrinsic renal disease2. Intrinsic renal disease3. Post - renal3. Post - renal



acute renal failure:acute renal failure: Causes of Causes 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 or *Circulatory shock due to hemorrhage 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 affectingrenal 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→ Glomerulidiseases affecting→ Glomeruli

→→ Blood vesselsBlood vessels→→ Renal tubulesRenal tubules



Acute renal failureAcute renal failure3. Post-renal causes of ARF are due to3. 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 renalBilateral obstruction of ureters or renalpelvices.pelvices.

b. bladder obstructionb. bladder obstructionc. uretheral obstructionc. uretheral obstruction

*Causes of obstruction could be*Causes of obstruction could be

1. stones 2. tumor 3. inflammation1. stones 2. tumor 3. inflammation→→ Obstruction of urine flow leads slowlyObstruction of urine flow leads slowlyprogressive destruction of renal tissues. Alsoprogressive destruction of renal tissues. Also

leads to infection which results in rapidleads 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 fluidThis may be due to blood loss or loss of intravascular fluid

into tissues as in cases of burns, crush injuries, sepsis →into tissues as in cases of burns, crush injuries, 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 GFRblood 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 bodywater and electrolytes. A decrease in blood flow leads to awater and electrolytes. A decrease in blood flow leads to a

decrease in GFR and thus decreasing the ability of thedecrease in GFR and thus decreasing the ability of thekidneys to excrete excess water and electrolyteskidneys to excrete excess water and electrolytes



Reversible pre-renal ARFReversible pre-renal ARF** Normally the kidneys can regulate their blood flow andNormally 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 liberationof prostaglandins.of prostaglandins.

b. A decrease in stretching of renal blood vesselsb. 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 byc. A vasoconstriction of efferent arteriols by

Angiotensin II: Ang iotensin II:

This effect is mediated through the release of renin fromThis effect is mediated through the release of renin from juxtaglomerular apparatus. juxtaglomerular apparatus.

When the above mechanisms fail to maintain bloodWhen the above mechanisms fail to maintain blood

Flow, then GFR decreased and this leads to formationFlow, 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. prolongedprolonged kidneys under perfusion (i.e. prolongedischemia of renal tubules which follows circulatoryischemia of renal tubules which follows circulatoryshock). 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 necrosisoxygen to them and this causes acute tubular necrosis

and shedding of tubular cells into tubular lumensand shedding of tubular cells into tubular lumensobstructing them.obstructing them.

2.2. Toxic effects of drugs and chemicalsToxic effects of drugs and chemicals

3.3. Conditions affecting intra-renal arteries and arteriolsConditions affecting intra-renal arteries and arteriols

like vasculitis, hypertension and disseminatedlike vasculitis, hypertension and disseminatedintravascular 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 failureunderlying condition that caused the renal failureand 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 urinarytract 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 lowGFR and poor tubular absorption and does notGFR and poor tubular absorption and does notmean normal kidney excretory function.mean normal kidney excretory function.




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 onThe rate of the increase of these substances depends oncatabolic 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 massiveis common specially if there massivebreak down of tissues, hemolysis and acidosis.break down of tissues, hemolysis and acidosis.

*Hyperkalemia*Hyperkalemia must be corrected because of its effectmust 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, cardiacconcentration is more 7 mmol/l, cardiacarrest may occur.arrest may occur.

*Dilutional hyponatremia (reduced plasma Na*Dilutional hyponatremia (reduced plasma Na++))

occurs if water intake is free or inappropriate amountoccurs if water intake is free or inappropriate amount

of intravascular water is given.of intravascular water is given.




2. blood chemistry abnormalities (Cont.)2. blood chemistry abnormalities (Cont.)*Hypocalcaemia*Hypocalcaemia: is due to less: is due to less

1,25-dihydroxycholicalciferol which is formed in the1,25-dihydroxycholicalciferol which is formed in thekidney.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 metabolicacidosis)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 erythropoietinproduction).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 from An irreversible deterioration in renal function resulted fromirreversible loss of large number of functioning nephrons.irreversible loss of large number of functioning nephrons.

CRF occurs over a period of years.CRF occurs over a period of years.In CR, there is loss of excretory, metabolic and endocrineIn CR, there is loss of excretory, metabolic and endocrinefunctions of the kidney.functions of the kidney.

The clinical signs and symptoms of CRF are sometimesThe clinical signs and symptoms of CRF are sometimes

referred to asreferred to as

UREMIA.UREMIA.

Causes:Causes: Any factor or condition which destroys the normal function Any factor or condition which destroys the normal functionand structure of the kidneysand 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 belowuntil 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 mellitus2. Immunological disorder → glomerulonephritis2. Immunological disorder → glomerulonephritis

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

4. primary tubular disorder → nephrotoxins like4. primary tubular disorder → nephrotoxins likeanalgesics andanalgesics andheavy metalheavy 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

Cli i l F f CRFCli i l F t f CRF



Clinical Features of CRFClinical Features of CRF**Early stageEarly stage::CRF is often asymptomatic. Biochemical examinationCRF is often asymptomatic. Biochemical examination

shows an elevated blood urea and creatinineshows an elevated blood urea and creatinineconcentration.concentration.NocturiaNocturia may be an early symptom and it is due o loss of may be an early symptom and it is due o loss of concentration ability of the kidneys.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 likecomplaints which are not renal in origin likebreathlessness 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. Therespiration 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 amongmuscle twitching drowsiness and coma are amonglate signslate signs and symptoms of CRF.and symptoms of CRF. Actually, in late stage of CRF almost every body system is Actually, in late stage of CRF almost every body system isaffected.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 metabolic2. 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 capillary3. 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 and4. 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 theseverity of renal failure and anemia contributes to manyseverity of renal failure and anemia contributes to many

non-specific symptoms of CRF.non-specific symptoms of CRF.

B b liti f CRF (B b liti f CRF (

ll



Bone abnormalities of CRF (Bone abnormalities of CRF (renalrenalosteodystrophyosteodystrophy))

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 intestinefrom intestine hypocalcaemia, this causes:hypocalcaemia, this causes:A. Reduction in bone calcification.A. Reduction in bone calcification.B. HyperparathyroidismB. Hyperparathyroidism Increased boneIncreased bone

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

toto hyperphosphotaemiahyperphosphotaemia which stimulates thewhich 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 andhyperthyroidism, vitamin D deficiency andelectrolytes disturbances.electrolytes disturbances.

Neuropathy of CRFNeuropathy of CRFIs due to demyelination of nerve fibers (theIs due to demyelination of nerve fibers (thelonger 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

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Chronic Renal FailureChronic Renal FailureEndocrine disorders of CRFEndocrine disorders of CRF

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

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

hyperphosphotaemiahyperphosphotaemia

Amenorrhea Amenorrhea ( 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 inHowever a decreased renal metabolism of insulin in

CRF may reduce the daily requirements of insulin inCRF may reduce the daily requirements of insulin in

Diabetics.Diabetics.

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Chronic Renal FailureChronic Renal FailureMetabolic acidosisMetabolic acidosis

The increased HThe increased H++ leads to exchange of Hleads to exchange of H++ instead of Cainstead of Ca2+2+ in the bone and thisin the bone and thisaggravating the metabolic disease of theaggravating the metabolic disease of the

bone of CRF.bone of CRF.The respiration is strongly stimulated byThe respiration is strongly stimulated bymetabolic acidosis. The increasedmetabolic acidosis. The increasedrespiratory activity is an attempt to reducerespiratory activity is an attempt to reduceHH++ concentration by blowing of COconcentration by blowing of CO22..

PlasmaPlasma PPH less than 6.8 leads to comaH 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 develop80% 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++ andandfluid.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 speciallyThese hormones are increased in CRF speciallyif there is under-perfusion of renal tissues due toif there is under-perfusion of renal tissues due tovascular diseases.vascular diseases.

** Atherosclerosis Atherosclerosis is common and it is acceleratedis common and it is acceleratedby the hypertension.by the hypertension.

** Vascular calcificationVascular calcification may also occur in CRFmay also occur in CRF

** PericarditisPericarditis 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, theIf water and food are not restricted in complete CRF, thefollowing may occur:following may occur:

1. Generalized edema.1. Generalized edema.

2. High urea and creatinine plasma2. High urea and creatinine plasmaconcentration.concentration.3. High K3. High K++ and POand 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, theDue to decreased cellular and humoral immunity, theCRF patients are susceptible to infection.CRF patients are susceptible to infection.

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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 theWhen hypertension develops, it will increase theseverity of renal failure because hypertensionseverity of renal failure because hypertensioncauses further damage to glomeruli and renalcauses further damage to glomeruli and renal

blood vessels.blood vessels.

*Conditions like renal artery stenosis reduce*Conditions like renal artery stenosis reducerenal blood flow and therefore reducing GFR andrenal blood flow and therefore reducing GFR andthis leads to retention of water and developmentthis leads to retention of water and development

of hypertension.of hypertension.*Chronic glomerulonephrirtis causes thickening*Chronic glomerulonephrirtis causes thickeningof glomerular capillary membrane and thereforeof glomerular capillary membrane and thereforedecreasing GFR and subsequently developmentdecreasing 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 retentionabsorption which leads to water retentionand subsequently development of and subsequently development of hypertension.hypertension.

* Conditions that increase* Conditions that increase reninrenin secretionsecretion

leads to formation of angiotensin II, whichleads to formation of angiotensin II, whichcauses retention of Nacauses retention of Na++ and water andand water andvasoconstriction and this will lead tovasoconstriction and this will lead tohypertension.hypertension.



Replacement of renal function in renalReplacement 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 whichIt is essential to get rid of these toxic substances whichworsen the condition and affect other body systems. It isworsen the condition and affect other body systems. It isalso important to replace the endocrine function of thealso important to replace the endocrine function of thefailing kidneys.failing kidneys.

**It is possible to replace the excretory function of the**It is possible to replace the excretory function of thefailed kidneys byfailed 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 acuterenal 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 metabolicfunctions of the kidney. These function could be resumedfunctions of the kidney. These function could be resumedby kidney transplant.by kidney transplant.



Basic principle of dialysisBasic principle of dialysis

Please see Textbook of medical physiologyPlease see Textbook of medical physiology

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

Documents

8-Renal Pa Tho Physiology (8)