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Chemical Pathology Of Kidney Diseases(0).pptx
1.
2.
3. Renal failure
• Renal failure is defined as a significant loss of renal function in
both kidneys to the point where less than 10 to 20% of normal
GFR remains.
• Renal failure may occur as an acute and rapidly progressing
process or may present as a chronic form in which there is a
progressive loss of renal function over a number of years.
• Acute renal failure has an abrupt onset and is potentially
reversible.
• Chronic failure progresses slowly over at least three months
and can lead to permanent renal failure.
4. Pathophysiology of Renal Failure
• In renal failure there is either glomerular or tubular dysfunction
e.g.
– glomerulonephritis primarily causes of glomerular damage
– aminoglycoside nephrotoxicity is mainly in tubular
• Glomerular dysfunction- As the main function of glomeruli is
filtration, glomerular dysfunction leads to fall in GFR with retention of
those substances usually cleared by filtration, including water.
• Tubular Dysfunction- As the main function of tubules is reabsorption
tubular failure results in the voiding of large volumes of dilute urine
(polyuria) of low specific gravity, along with electrolytes and
nutrients.
5. Acute renal failure
• Sudden decrease in renal function.
• Acute renal failure may be pre-renal, intra-renal or post-
renal in nature. Acute renal failure is often reversible so
long as permanent injury to the kidney has not
occurred.
• Manifestations
– Oliguria (reduced urine output)
– Possible edema and fluid retention
– Elevated blood urea nitrogen levels (BUN) and serum
creatinine
– Alterations in serum electrolytes
6. Causes of Acute Renal Failure
Common causes of acute renal failure are:
Glomerulonephritis, Myocardial infarction,
rhabdomyolysis, flow obstruction, hemolytic uremic
syndrome, decrease blood volume
Acute Renal Failure classified as pre-renal failure,
intra-renal failure and post-renal failure
• Pre-renal failure
– Results from impaired or reduced blood flow to the
kidney
– Possible causes: shock, hypotension, anaphylaxis,
ischemic formation
7. Causes of Acute Renal Failure
• Intra-renal failure
– Results from acute damage to renal structures
– Possible causes:
• acute glomerulonephritis, pyelonephritis
• May also result from acute tubular necrosis (ATN)
• damage of kidney structure from exposure to
toxins, solvents, drugs and heavy metals; ATN is the
most common cause of acute renal failure
• Post-renal failure
– Results from conditions block of urine outflow
– Possible causes: obstruction of urine outflow by
calculi, tumors, prostatic hypertrophy
8. Symptoms of acute renal Failure
• Decreased kidney function (electrolyte imbalance)
• Obstruction in the urinary tract
• Blood in urine
• Reduced urine output
• Dehydration
• Detectable abnormal mass
• Pale skin
• Poor appetite
9. Treatment of acute renal failure
• Treatment
– Prevention of acute renal failure through support
of blood pressure and blood volume
– Correction of fluid and electrolyte imbalances
– Dialysis, which may be employed while the
kidneys are in the recovery phase
– Low protein, high carbohydrate diet to
minimize the formation of nitrogenous
wastes
10. Chronic renal failure
• Chronic renal failure is the end result of progressive kidney
damage and loss of function. Chronic renal failure is often
classified into four progressive stages based on the loss of GFR.
• Normal GFR = 90 - 120 ml/min/1.72m2 (women)
• 100 - 130 ml/min/1.73m2 (men)
Stages of Chronic Renal Failure
Diminished renal reserve —GFR decreased to 35 to 50% of normal
Renal insufficiency —GFR decreased to 20 to 35% of normal
Renal failure —GFR reduced to less than 20% of normal
End-Stage Renal Disease —GFR is less than 5% of normal
11. Causes of chronic renal failure
– Chronic glomerulonephritis
– Chronic infections
– Renal obstruction (prolonged)
– Exposure to toxic chemicals, toxins or
(aminoglycoside antibiotics and nephrotoxicity)
– Diabetes Mellitus
– Hypertension
– Nephrosclerosis (atherosclerosis of the renal artery)
– Diabetic nephropathy
– Alport syndrome (inherited disorder causes progressive
kidney damage and eye defects)
– Polycystic kidney disease
– Interstitial nephritis or pyelonephritis
12. Symptoms of chronic renal failure
– Until every kidney function remains, chronic renal
failure may not developed
– Anemia, increasedlevels of phosphates(in blood)
are complications of kidney failure
– Malaise
– Dry skin
– Poor appetite
– Vomiting
– Bone pain
– metallic taste in mouth
– detectable abdominal mass
13. Manifestations of chronic renal failure
– Renal failure is a multisystem disease
System Effect Cause
Body fluids Polyuria Metabolic acidosis
Metabolic acidosis Reduced H+ excretion
Abnormal levels of Na+, K+,
Ca2+, PO4-
Loss of tubular function
Hematologic Anemia, excess bleeding Impaired erythropoietin
Cardiovascular Hypertension, edema Activation of renin–
angiotensin system
Gastrointestinal tract Anorexia, nausea Accumulation of metabolic
wastes
Neurologic Uremic encephalopathy Accumulation of ammonia
and nitrogenous waste
Musculoskeletal Muscle and bone weakness
(“Renal Osteodystrophy”)
Loss of calcium and
minerals
14. Treatment of chronic renal failure
• Careful management of fluids and
electrolytes
• Prudent use of diuretics
• Careful dietary management;
restriction of dietary protein intake
• Recombinant erythropoietin to treat
anemia
• Renal dialysis
• Renal transplantation
15. Disorders of the bladder and urethera
–Urine reflux: abnormal movement of
urine fromthe bladder into ureters or
kidneys.
–Neurogenic bladder: disease of the
central nervous system or peripheral
nerves involved in the control of
micturition.
–overactive bladder: chronic condition of
the bladder in the urinary tract that
causes sudden urges to urinate.
16. Aminoglycoside antibiotics and
nephrotoxicity
• Aminoglycoside (streptomycin,
gentamicin and kanamycin) toxicity is
most likely to occur in elderly people,
those with renal insufficiency or with
chronic use.
• Concurrent use of loop diuretics may also
compound the adverse renal effects of
the aminoglycosides.
18. KIDNEY STONES
A kidney stone is a hard solid mass of
material that forms in the kidney from the
substances in the urine.
Kidney stones or calculi develop as a result of
various metabloic disorders which affect the
fate of calcium and other mineral elements in
the body.
Stones may be formed in the kidney, urinary
bladder,ureter and urethra
19. Meaning:-
A kidney stone, also known as a renal
calculus or nephrolith, is a solid piece of
material which is formed in the kidneys from
minerals in urine
22. Type of renal stone:-
There are mainly 5 types:-
1.
2.
3.
4.
5.
Calcium oxalate stone (Is the most common 80% )
Calcium phosphate stone
Struvite stone (Triple stone)
Uric acid stone
Cystic stone
23. 1.Calcium oxalate stone (Is the most common 80% )-
Caused by super -saturation of urine with calcium & oxalate
Calcium oxalate stone tend to form in alkaline chemistry
( Avoid food high in oxalate(beer, wheat germ, spinach)
2. Calcium phosphate stone (5-10%):- Caused by
super -saturation of urine with calcium phasphate.
Calcium phosphpate stone tend to form in alkaline chemistry
(Avoid food high in calcium (Milk & dairy product)
3. Struvite stone (Triple phosphate stone):-
Caused by urea splitting bacteria (Proteus, Pseudomonas, Klebsiella,
Staphylococcus) –more common women then the man because of UTI
Struvite stone stone tend to form in alkaline chemistry
24. 4. Cystic stone (10-15%):- Caused by cystine crystal
formation
Cystic stone stone tend to form in Acidic urine
( cystine source Avoid meat milk ,cheese, Egg)
5. Uric acid stone (5-10%):-Caused by excessive
dietary purine or gout
Uric acid stone tend to form in Acidic urine
(Avoid purine sources eg. Meats, gravies, red wine)
26. Clinical manifestation:-
Severe pain in the side and back, below the
ribs
Pain that spreads to the lower abdomen and
groin
Pain that comes in waves and fluctuates in
intensity
Pain on urination
Cloudy or foul-smelling urine
Nausea and vomiting
Fever and chills if an infection is present
Urinating small amounts of urine
46. Functions of Kidney
• Formation of Urine as the waste product
• Excretion of substances – Urea,
Creatinine and Uric acid
• Regulation of water, electrolytes & acid-base
balance
• Production of hormones – Erythropoitin,
renin & calcitriol
47. Assessment of Renal Function
• Assessment of the extent of renal damage
• Monitoring the progression of renal disease
• Monitoring & adjusting the dose of renal toxic
drugs
Renal Function Test (RFT) is devised to give
information regarding following parameters
Renal tubular function
Renal Glomeruli Function
• Renal blood flow
• Glomerular Filtration Rate
• Urine output
48. RFT
• a) those which measure GFR
• b ) those which study tubular function
49. RFT Classification
1. Urine analysis
- Physical examination
- Chemical examination
- Microscopic examination
2. Assessment of Glomerular function
- Renal Clearance tests
- Blood analaysis of Urea &
Creatinine
- Proteinuria
- Hematuria
50. RFT Classification
3. Tests to measure renal plasma flow
- Para-aminohippurate test
4. Tests for assessment of tubular function
- Urine concentration test
- Urine dilution test
- Specific proteinuria or
tubular proteinuria
- aminoaciduria
- Phenolsulfonphthalein test (PSP)
5. Renal Biopsy
- to confirm the diagnosis &
renal diseases
51. RFT - Tests for Glomerular Function
Renal Clearance Tests
To assess the rate of glomerular filtration &
renal blood flow.
“The renal clearance of a on substance is defined as
the volume of plasma from which the substance is
completely cleared by the kidneys per minute.”
This
- plasma conc. Of the substance & it’s
excretary rate
Depend
On
- GFR
- Renal plasma flow
52. Renal Clearance Tests
• The GFR (Normal = 120 ml/minute )
• Usually equal to clearance of that substance and is
calculated by the following equation
C = U x V
P
where,
C = clearance of the substance (ml/mt)
U = Conc.of substance in urine (mg/L)
P = Conc.of substance in plasma(mg/L)
V = Vol.of the urine passed per sminute
53. Renal Clearance Tests
• GFR – Normal 120 ml/minute
• Lower than normal GFR indicate
- Acute tubular necrosis
- Glomerulonephritis
- Shock
- Acute Nephrotic syndrome
- Ac. & Ch. Renal failure
• In order to determine the GFR, the substance should be
selected in such a way that it:
- freely filtered by glomerulus
- should not be reabsorbed or secreted
- should not be metabolized in the kidney
- should not be toxic
- should not be affected by dietary intake
54. • The substances which are used for Clearance tests
include :
Endogenous - Creatinine
- Urea
- Inulin
Exogenous
55. Creatinine Clearance Test
• Based on the rate of excretion by the kidneys of
metabolocally produced creatinine
• Creatinine freely filtered in the glomerulus
• Not reabsorbed by the tubules
(a small amount of creatinine is produced by the
tubules)
56. Creatinine Clearance Test
• Creatinine clearance is determined by
- collecting urine over 24hrs. Period
- a sample of blood is drawn
during the urine collection
period.
Creatinine Clearance = U x V
P
U = Urinary creatinine(mg/L)
P = Plasma creatinine (mg/L)
V = Volume of urine per minute
57. Creatinine Clearance Test
• Creatinine Clearance Normal range 90-120 ml/mt
• ↓ Creat. Clearance is very sensitive indicator of
decreased GFR
• ↓ GFR may be caused by
Acute or Chronic damage to glomerulus or any of
its components
• ↓ Blood flow to glomerulus may also produce
decreased creat.clearance
58. Urea Clearance Test
• The sensitivity of urea clearance is much less than
the creatinine clearance because—
-plasma conc. Of urea is affected by number of
factors
e.g : dietary protein
fluid intake
infection
surgery, etc…
- Approximately 40 % of filtered urea is normally
reabsorbed by the tubules.
• Normal value of Urea clearance : 75 ml/mt.
59. Inulin Clearance Test
• Method of choice when accurate determination of
GFR is required.
• Inulin is polysacharide of Fructose.
freely filtered by glomerulus
not reabsorbed
not secreted or metabolically altered by the renal
tubule.
• Normal value : 120 ml/mt.
Disadvantages : need for its IV adminstration
technically difficulty of analysis
60. Blood analysis of Urea & Creatinine
• Impairment of renal function results in elevation of
Blood Urea ( normal : 20 – 40 mg/dl )
Creatinine ( normal : 0.5 – 1.5 mg/dl )
• Plasma urea is less reliable than creatinine because
it is affected by dietary protein & liver function
• So, Creatinine is more sensitive Renal Function Test.
61. • Uremia :
• Pre-renal uremia :
- Dehydration
diarrhea,
severe vomiting
- Diabetic coma.
- severe burns
- intestinal obstruction ,
- Fever and severe infections
