Diseases Affecting Tubules and InterstitiumAcute Tubular Necrosis:

• It is a clinicopathological entity characterized morphologically by destruction of tubular epithelium and clinically by acute renal failure.

• It can be caused by;1. Ischemia.2. Direct toxic injury of tubules (drugs, contrast dyes, myoglobin, radiation).3. hypersensitivity reaction to drugs4. DIC5. Urinary tract obstruction.

Acute Tubular Necrosis-cont

• ATN accounts for some 50% of cases of acute renal failure in hospitalized patients.

• It is a reversible renal lesion that arises in a variety of clinical settings:

1.Ischemic ATN.

2.Nephrotoxic ATN (gentamicin, contrast agents, heavy metals, and poisoning organic solvents).

Morphology

• Ischemic ATN is characterized by focal tubular epithelial necrosis at multiple points along the nephrone.

• The straight portion of the proximal tubule and the ascending limb of Henle’s loop in the medulla, are especially vulnerable.

• Eosinophilic hyaline casts as well as pigmented granular casts, are common in DCT and CD.

• Other features are interstitial edema and leukocytic infiltration.

• Toxic ATN is manifested by injury most obviously in the proximal convoluted tubules.

Clinical course• It is highly variable, but in classical cases is divided into;

1. Initiation phase, lasting for about 36 hours, is dominated by medical, surgical, or obstetric events in the ischemic form. The only indication of renal involvement is mild oliguria.

2. Maintenance phase, characterized by sustained oliguria to 40-400 ml/24 hrs, and other manifestations of uremia.

3. Recovery phase, there is steady increase in urine output that may reach 3L/24 hrs.

Tubululointerstitial Nephritis Induced By Drugs and Toxins

Toxins and drugs can produce renal injury in at least 3 ways:

1. By triggering an interstitial immunologic reaction.

2. Acute tubular necrosis.

3. Can have mild but cumulative injurious effect on tubules, resulting in chronic renal failure.

Urinary Tract Infection Pyelonephritis (PN)

• It is one of the most common diseases of the kidney.

1. Acute pyelonephritis, caused by bacterial infection.

2. Chronic PN, is more complex disorder, bacterial infection plays a dominant role, but other factors (Vesicoureteral reflux, obstruction), are involved also in the pathogenesis.

Acute Pyelonephritis ,• Is an acute suppurative inflammation of the kidney caused by

bacterial and sometimes, other microorganisms.

• In over 85% of cases, gram negative bacilli are responsible.

• By far the most common is E. coli, followed by Proteus, Klebsiella, and Enterobacter.

• There are 2 routes by which the organism can reach the kidneys;1. From the lower urinary tract (much common).2. Through the blood stream (much less common).

Pathways of Renal Infection

• Morphology, the hallmark is patchy interstitial suppurative inflammation, tubular leukocyte casts and tubular necrosis.

• Three complications are encountered:

1. Papillary necrosis, particularly in diabetics and those with urinary tract obstruction.

2. Pyonephrosis, when there is total or almost complete obstruction, especially when it is in the upper part of the urinary tract.

3. Perinephric abscess.

• The end-result is healing by scars formation, almost always associated with deformity of the underlying calyces and pelvis.

Clinical Course ,• The condition is associated with predisposing factors, which

include,1. U-T obstruction.2. Instrumetation of the urinary tract.3. Vesicoureteral reflux.4. Pregnancy.5. Patient's sex.6. Pre-existing renal lesion.7. Diabetes mellitus.8. Immunodeficiency.

• The onset is sudden with pain at the costovertebral angle and systemic evidence of infection, such as fever and malaise.

• There is also dysuria, frequency and urgency.

• Urine contains pus cells and leukocyte casts

Chronic Pyelonephritis• It is characterized by chronic tubulointerstitial inflammation

and renal scarring associated with pathologic involvement of the calyces and pelvis.

• It is an important cause of end-stage kidney disease.

• It can be divided into 2 forms:

1. Reflux nephropathy, which is the more common. It occurs early in childhood.

2. Obstructive nephropathy, which could be unilateral or bilateral.

Morphology ,

• The characteristic changes are seen grossly. The kidneys are irregularly scarred; if bilateral, the involvement is asymmetric.

• The scars overlie dilated, blunted or deformed calyces, mostly in the upper and lower poles.

• Microscopically, tubules are atrophic and dilated in others. There are varying degrees of chronic interstitial inflammation and fibrosis in the cortex and medulla.

Chronic pyelonephritis

Xanthogranulomatous Pyelonephritis

• Is relatively rare form of chronic PN, characterized by accumulation of foamy macrophages, plasma cells, lymphocytes, neutrophils and occasional giant cells.

• Often associated with Proteus infection and obstruction.

• Grossly, the lesion produces large, yellowish/orange mass that may be confused with renal cell carcinoma

Urinary Tract Obstruction (Obstructive Uropathy)

• Recognition of obstruction is important, because it increases susceptibility to infection and to stone formation, and if unrelieved, it leads to permanent renal atrophy, termed hydronephrosis.

• The obstruction may be sudden or insidious, partial or complete, unilateral or bilateral, and it may occur at any level.

• The most common causes are:

1. Congenital anomalies, posterior urethral valves and urethral strictures.

2. Urinary calculi.3. Prostatic hyperplasia.4. Tumors.5. Inflammation.6. Pregnancy.7. Functional disorders, neurogenic bladder.

• Pathogenesis, even with complete obstruction, glomerular filtration persists for sometimes.This continued filtration leads to pelvicalyceal dilation, which leads in turn to renal atrophy and hydronephrosis

Morphology,• When the obstruction is sudden and complete, there is

mild hydronephrosis, but if the obstruction is subtotal or intermittent, there is more severe hydronephrosis.

• Depending on the level of urinary block, the ureter and the bladder may be affected too.

• In advanced cases, the kidney may become transformed into a thin-walled cystic structure .

Hydronephrosis:

• Dilatation of renal pelvis and calyces associated with progressive atrophy of the renal parenchyma due to obstruction of urine out flow.

Urolithiasis:

• Stones may arise at any level of the urinary tract, but most arise in the kidney.

• Men are affected more than women.

• The peak age at onset is 20-30 years.

Cause and pathogenesis• There are 4 main types of calculi :

1. Calcium containing (70%), composed of pure calcium oxalate or mixed with calcium phosphate.

2. Triple stones (15%), composed of magnesium ammonium phosphate (MAP).

3. Uric acid stones (5-10%).

4. Cystine stones (1-2%).

• There are many factors that lead to initiation of stones:

1. Increased concentration of stone constituents.

2. Changes in urinary pH.

3. Urinary tract obstruction.

4. UT infection.

Morphology:

• stones are bilateral in about 80% of patients.

• The favored sites for their formation are within the renal calyces and pelvis, and in the bladder.

• The stones may have smooth contours or irregular external surface and on occasion they develop branches (stag-horn stones) which take a shape of the pelvicalyceal system.

Clinical course

• Stones are of importance when they

– obstruct urinary flow – produce infection, – ulceration – bleeding.