Disease affecting tubules and interstitium

Disease Affecting Disease Affecting Tubules & InterstitiumTubules & Interstitium

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

Most of tubular injurytubular injury also involve the interstitium.

It could be Inflammatory as interstitial nephritis Ischemic as acute tubular necrosis

Portal circulation of the kidney 2 arterial capillaries

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Ares of collecting tubules and loops of Henley's

I- I- Tubulo-Interstitial Nephritis (TIN)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.

I- I- Tubulo-Interstitial Nephritis (TIN)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,..)

11--Acute pyelonephritisAcute pyelonephritis

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, ..

Acute pyelonephritisAcute pyelonephritis

Routes of infectionRoutes 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.

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.

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.

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.


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 .

Abscess formation within renal parenchyma

Large masses of neutrophils extend within the nephron into collecting tubules


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)


A second infrequent form of pyelonephritis is necrotizing papillitis.

In which there is necrosis of renal papillae (at the tip of renal pyramids).

Necrotizing papillitis


Necrotizing Papillitis. There is sharp grey white to yellow necrosis

of papillae. It is seen more commonly in diabetes

mellitus who develop acute pyelonephritis.

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

At high magnification, many neutrophils are seen in the tubules and interstitium in a case of acute pyelonephritis

Clinical Picture

Onset is sudden with pain at costo-renal angle.

Fever, rigors and malaise. Urine analysis :

Pyuria,. WBCs casts, Positive urine culture.

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.

Chronic PyelonephritisChronic 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:

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).

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.

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

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.

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

Both lymphocytes and plasma cells are seen at high magnification in

this case of chronic pyelonephritis

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

Drug-Induced Interstitial Nephritis

1- Acute drug induced interstitial nephritis;

It occur due to adverse reaction to many drugs as

Penicillin, Rifampicin, Phenylbutazone and others,..

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.

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.

Acute drug induced…

Morphology: the interstitium is infiltrated by

eosinophils in large amount and also other mononuclear cells.

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The interstitium is infiltrated by eosinophils in large amount And also other mononuclear cells.

2-Analgesic nephropathy

Patients who consume large amount of analgesics may develop interstitial nephritis associated with papillary necrosis.

These analgesic include Phenacetin , Acetaminophin, Aspirin, …

2-Analgesic nephropathy

Pathogenesis: Phenacetin injures the cells by oxidative

damage. Aspirin inhibit PG production and thus

inhibit its vasodilatory effects and predispose to papilla to ischemia.

Analgesic nephropathy

Morphology: Papillary necrosis is the characteristic

finding. The papillae appear yellowish brown due

to accumulation of drug products.


Microscopically

The papilla show:- Coagulative necrosis With loss of cellular details and Preservation of tubular outline.


Clinically,

It may present with CRF and hypertension . Cessation of analgesic intake may improve

renal function.

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).


Other causes of ARF include

1. Severe glomerular diseases,

2. Acute papillary necrosis,

3. and others.

ATN

ATN is a reversible renal lesion.

Its reversibility adds to its clinical importance because proper treatment can safe patient life.

ATN

ATN can results either from reduction of blood flow and shock

(Ischemic ATN) due to toxins as carbon tetrachloride

(Nephrotoxic ATN)

Nephrotoxic ATN

ATN pathogenesis

Two events occur in ATN:1- Tubular injury2- Intra renal vasoconstriction

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.

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.

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

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.

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) .

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

Casts in distal & collecting tubules

The tubular vacuolization and dilation . This is representative of acute tubular necrosis (ATN)

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.

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 %

Causes of obstructionCauses of obstruction

Disease affecting tubules and interstitium

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