2. Presented By
Prof. Dr.
Nabil Tadros Mikhail
MBBS, MS Pathol., PhD Pathol.
Prof. of Pathology
Alexandria University - Egypt
Consultant & Chief Pathologist
King Fahad Central Hospital
Gizan - KSA
3.
4. Most of tubular injury also involve the
interstitium.
It could be
Inflammatory as interstitial nephritis
Ischemic
as acute tubular necrosis
8. (I- Tubulo-Interstitial Nephritis (TIN
A group of inflammatory diseases
affected the interstitium and tubules.
The glomeruli may be spared
altogether or affected only late in the
course of disease.
9.
10.
11.
12. (I- Tubulo-Interstitial Nephritis (TIN
Most of TIN caused by infection
Renal pelvis is also affected and hence
the name pyelonephritis.
The term interstitial nephritis is reserved
for cases of non infectious origin as
(drugs, hypokalemia,..(
13. Acute pyelonephritis-1
It is a common suppurative inflammation
of the kidney and renal pelvis caused by
bacterial infections.
The causative organism is most
commonly E coli.
Other organisms could be involved as
proteus , klebsiella ,pseudomonas, ..
14. Acute pyelonephritis
Routes of infection:
Two routes are recognized
1- Ascending infection: this is the most
common route. Ascending infection
occur from the lower urinary tract
2- hematogenous route; infection occur
through blood stream.
15.
16. Predisposing factors
1- Urinary obstruction: It result in stasis
which facilitate bacterial growth.
2- Vesicoureteral reflux (VUR(; It can be
congenital or acquired. Incompetence of
vesicoureteral orifice allows bacteria to
ascend the ureter into pelvis.
3- Instrumentation; as catheterization.
17. Predisposing factors
4- pregnancy: 6% of pregnant has
bacteriuria during pregnancy
5- diabetes mellitus: increases the risk of
pyelonephritis
6- Sex: common in females due to short
urethra
7-Immunosuppression and deficiency.
18.
19. Morphology Of
Acute Pyelonephritis
One or both kidney may be involved.
Affected kidney may be slightly
enlarged.
Characteristically discrete yellowish
raised abscesses are apparent on
renal surface.
20.
21.
22. Morphology Of
Acute Pyelonephritis
Microscopically:
Suppurative necrosis or abscess
formation within renal parenchyma.
Large masses of neutrophils extend
within the nephron into collecting
tubules, giving rise to white cell
casts in urine .
24. Large masses of neutrophils extend within the nephron into collecting tubules
25. Morphology Of
Acute Pyelonephritis
Microscopically:
Typically the glomeruli are spared
and resist infection.
If obstruction is complete
suppurative exudate may be unable
to drain and fill renal pelvis
(pyonephrosis)
26. Morphology Of
Acute Pyelonephritis
A second infrequent form of pyelonephritis
is necrotizing papillitis.
In which there is necrosis of renal papillae
(at the tip of renal pyramids).
28. Morphology Of
Acute Pyelonephritis
Necrotizing Papillitis.
There is sharp grey white to yellow necrosis
of papillae.
It is seen more commonly in diabetes
mellitus who develop acute pyelonephritis.
29. This is an ascending bacterial infection leading to acute pyelonephritis.
Numerous PMN's are seen filling renal tubules across the center
and right of this picture
30. At high magnification, many neutrophils are seen in the tubules and interstitium
in a case of acute pyelonephritis
31. Clinical Picture
Onset is sudden with pain at costo-renal
angle.
Fever, rigors and malaise.
Urine analysis :
Pyuria,.
WBCs
casts,
Positive urine culture.
32. Clinical Picture ..
The disease tend to be benign and self
limited.
Repeated attacks may lead to chronicity
(chronic pyelonephritis).
Those with necrotizing papillitis may be
associated with acute renal failure and
poor prognosis.
33. Chronic Pyelonephritis
Chronic pyelonephritis is defined as
interstitial inflammation and scarring
of renal parenchyma with deformity
of pelvicalyceal system.
Chronic pyelonephritis is an
important cause of chronic renal
failure.
Two forms are found:
34.
35.
36.
37.
38. Chronic Pyelonephritis
1- chronic obstructive pyelonephritis:
Associated with urinary obstruction.
Recurrent infection is
superimposed on obstructive lesion
leading to chronic pyelonephritis.
The disease may be
Bilateral (urethral obstruction) or
Unilateral (calculi in ureter).
39. Chronic Pyelonephritis
2- Chronic reflux associated
pyelonephritis:
It is also called reflux nephropathy.
It result from repeated infection on those
with vesicoureteral reflux.
It may be unilateral or bilateral involve
both kidneys and lead to CRF.
40.
41. Morphology
Macroscopically:
one or both kidney may be involved.
In bilateral involvement ,the kidneys are
not equally contracted with uneven
scarring.
Scars involve renal pelvis and calyces
resulting in blunted and deformed
calyces
42. Morphology
Microscopically; is non specific.
Uneven interstitial fibrosis and inflammatory
infiltrates of lymphocytes and plasma cells.
Tubules are either contracted or dilated and
lined atrophic epithelium and contain colloid
casts (resemble thyroid).
Glomeruli is usually normal except late
when glomerulosclerosis occur.
43. The large collection of chronic inflammatory cells here is in a patient
with a history of multiple recurrent urinary tract infections.
This is chronic pyelonephritis
44. Both lymphocytes and plasma cells are seen at high magnification in
this case of chronic pyelonephritis
45. Clinical Picture
May be asymptomatic and discovered late.
Hypertension may be found.
Bacteriuria is not always found.
Bilateral disease affect tubules mainly with
loss of concentrating ability leading to
polyuria and nocturia.
Late stages glomeruli is affected and CRF
occur
46. Drug-Induced
Interstitial Nephritis
1- Acute drug induced interstitial
nephritis;
It occur due to adverse reaction to
many drugs as
Penicillin,
Rifampicin,
Phenylbutazone
others,..
and
47. Drug-induced
Interstitial Nephritis
1- Acute drug induced interstitial nephritis;
The disease begins 15 days after exposure
to drugs and characterized by
Fever,
Eosinophilia,
Rash
Hematuria.
Acute renal failure and oliguria may develop in
50% of cases.
48. …Acute drug induced
Pathogenesis:
Both type I (IgE mediated)
and type IV (cell mediated)
hypersensitivity are found.
The drug act as hapten and become
bound to extracellular components of
tubular cells and become immunogenic.
49. …Acute drug induced
Morphology:
the interstitium is infiltrated by
eosinophils in large amount and also
other mononuclear cells.
50. The interstitium is infiltrated by eosinophils in large amount
And also other mononuclear cells.
Slide 21.57
51. Analgesic nephropathy-2
Patients who consume large amount of
analgesics may develop interstitial nephritis
associated with papillary necrosis.
These analgesic include
Phenacetin ,
Acetaminophin,
Aspirin, …
52. Analgesic nephropathy-2
Pathogenesis:
Phenacetin injures the cells by oxidative
damage.
Aspirin inhibit PG production and thus
inhibit its vasodilatory effects and
predispose to papilla to ischemia.
53. Analgesic nephropathy
Morphology:
Papillary necrosis is the characteristic
finding.
The papillae appear yellowish brown due
to accumulation of drug products.
56. )Acute tubular necrosis (ATN
ATN is characterized
Morphologically by destruction of tubular
epithelium and
Clinically by ARF .
The latter signifies an acute suppression of
renal function with urine flow falling within
24 hours to less than 400 ml (oliguria).
63. ATN pathogenesis
Two events occur in ATN:
1-
Tubular injury
2- Intra renal vasoconstriction
64. ATN pathogenesis
1- Tubular injury:
Tubular cells are sensitive to ischemia
and toxins.
These result in loss of polarity which
affect Na/K ATPase and lead to increase
Na delivery to distal tubules.
65. The tubular vacuolization and dilation here is representative of acute tubular necrosis
(ATN(, which has many causes. ATN resulting from toxins as ethylene glycol, usually has
diffuse tubular involvement, while if from ischemia (as in profound hypotension from
cardiac failure( has patchy tubular involvement.
66.
67. ATN pathogenesis
The latter cause vasoconstriction.
Further damage to tubules and the
resultant tubular debris could block
urine outflow and decrease GFR and
lead to oliguria
68. ATN pathogenesis
2- Intra renal vasoconstriction;
It results from
Activation of renin angiotensin system ,
Increase endothelin production,
Decrease nitric oxide and PGI2.
This vasoconstriction will decrease GFR
and produce oliguria.
69. ATN morphology
ATN is characterized by necrosis of
renal tubules.
Most lesions are common in outer
medulla (ascending limp and proximal
tubule(.
Tubular necrosis is often accompanied
with rupture of the basement membrane
(tubulorrhexis( .
70. ATN morphology
An additional feature is the presence of casts in
distal & collecting tubules.
They are composed of Tamm-Horsfall protein
(secreted normally( by renal tubules.
When crush injuries results in ATN the casts
are composed of myoglobin
If the patient survive epithelial regeneration
become apparent
72. The tubular vacuolization and dilation .
This is representative of acute tubular necrosis (ATN(
73. ATN clinical picture
The urine output falls suddenly between
50 and 400 ml/day (oliguric phase)
There is symptom and signs of uremia.
(rise of urea and creatinine(
With good medical care survival is the
rule.
74. ATN clinical picture
The recovery is accompanied by
Increase of urine volume up to 3 litre/day
(polyuric phase), because tubular function
is still impaired and serious electrolytes
imbalance occur in this period.
Finally urine volume return to normal and the
chance of recovery is around 90-95 %