The Urinary Tract - Kidney Diseases PDF

The Urinary Tract Kidney: Diseases Affecting Tubules and Interstitium Dr. Mohammed I. Malki Assistant Professor of Pathology College of Medicine, Qatar University Annex Building, Office 8 [email protected] Content Most forms of tubular injury also involve the interstitium: 1. Inflammatory disease...

The Urinary Tract Kidney: Diseases Affecting Tubules and Interstitium Dr. Mohammed I. Malki Assistant Professor of Pathology College of Medicine, Qatar University Annex Building, Office 8 [email protected] Content Most forms of tubular injury also involve the interstitium: 1. Inflammatory diseases • Tubulointestitial nephritis (pyelonephritis) 2. Acute tubular (kidney) injury • Toxic • Ischemic Normal Histology Tubulointerstitial Nephritis (TIN)  Inflammatory diseases of the kidneys affecting the interstitium and tubules  Late in the course: the glomeruli may be affected  Causes:  Mostly by bacterial infection with pelvis involvement: pyelonephritis (from pyelo, “pelvis”)  The term interstitial nephritis is typically used for non‐bacterial origin • Drugs • Metabolic disorders (hypokalemia) • Physical injury (irradiation) • Viral infections • Immune reactions  Both can be acute and chronic (regardless of the etiologic agent) Acute Pyelonephritis  Suppurative inflammation of the kidney and the pelvis  Usually caused by bacteria (E. Coli (common) , Klebsiella, Proteus, Enterobacter, Pseudomonas (associated with recurrent infections))  Typical manifestation of urinary tract infection (UTI) • Associated with lower UTI (cystitis, prostatitis, uretheritis) • Less common with upper UTI (pyelonephritis)  Pathogenesis:  Route of infection: • Lower urinary tract (ascending infection) • Through the bloodstream (hematogenous infection) Acute Pyelonephritis Seeding of the kidneys by bacteria ‐ Septicemia ‐ Infective endocarditis Pelvis: Pyelonephritis Ureters: Incompetence of the vesicoureteral orifice, resulting in vesicoureteral reflux (VUR). This will allows bacteria to ascend the ureter into the pelvis From the contaminated bladder urine, the bacteria ascend along the ureters Bladder: Expansive growth of the colonies & Moving against the flow of urine (obstruction, diabetes) Distal Urethra: Adhesion of bacteria to mucosal surfaces is followed by colonization Fimbriae (Instruments, Females) Congenital defect that results in incompetence of the ureterovesical valve Acquired in persons with a flaccid bladder resulting from spinal cord injury or with neurogenic bladder dysfunction secondary to diabetes Acute Pyelonephritis – Predisposing Factors  Urinary obstruction It results in stasis, which facilitate bacterial growth  Instrumentation of the urinary tract (catheterization)  Vesicoureteral reflux  Pregnancy  Female gender  Male gender and age • As s result of the development of prostatic hyperplasia, which causes urinary outflow obstruction  Preexisting renal lesions • Causing intrarenal scarring and obstruction  Diabetes mellitus • Infection and bladder dysfunction  Immunosuppression and immunodeficiency Acute Pyelonephritis – Morphology Gross Features:  One or both kidneys may be involved  The affected kidney may be normal in size or enlarged  Characteristically, discrete, yellowish, raised abscesses are grossly apparent on the renal surface Histological Features: First Form of AP:  Patchy interstitial purulent inflammation  Tubular destruction in the involved area  Neutrophilic casts in collecting ducts pyuria Acute pyelonephritis. The cortical surface is studded with focal pale abscesses. Between the abscesses there is dark congestion of the renal surface Ascending bacterial infection leading to acute pyelonephritis. Numerous PMN's are seen filling renal tubules These leukocytes may form into a cast within the tubule. Casts appearing in the urine originate in the distal renal tubules and collecting ducts. Acute Pyelonephritis – Morphology Second form of AP:  Necrosis of the renal papillae (papillary necrosis)  Three predisposing conditions: • Diabetes • Urinary tract obstruction • Sickle cell anemia  Gross Features: • Gray‐white to yellow necrosis of the apical two thirds of the pyramids • One papilla or several or all papillae may be affected  Microscopically: • The papillary tips show characteristic coagulative necrosis, with surrounding neutrophilic infiltrate The he pale white areas involving some or all of many renal papillae are areas of papillary necrosis Coagulative necrosis rimmed by acute inflammation Acute Pyelonephritis – Clinical Course  Sudden with pain at the costovertebral angle  Systemic evidence of infection • Chills • Fever • Malaise  Localizing urinary tract signs of • Dysuria, frequency, and urgency  The urine appears turbid due to the contained pus (pyuria)  Predisposing factors present • The disease may become recurrent or chronic • The development of papillary necrosis (poor prognosis) Chronic Pyelonephritis  Interstitial inflammation and scarring of renal parenchyma followed by the deformity of the pelvicalyceal system in patient with history of UTI  Important cause of chronic renal failure  Two Forms: Chronic obstructive pyelonephritis • Obstruction predisposes the kidney to infection • Recurrent infection is superimposed on obstructive lesion leading to recurrent bouts of renal inflammation and scarring, which eventually cause chronic pyelonephritis • The disease may be Bilateral (posterior urethral valves) or Unilateral (calculi in ureter) Chronic reflux‐associated pyelonephritis (reflux nephropathy) • Superimposition of a UTI on congenital vesicoureteral reflux • It may be Unilateral or Bilateral involve one or both kidneys (scarring & atrophy) lead to chronic renal insufficiency Chronic Pyelonephritis – Morphology Gross Features:  Scarring involving the pelvis or calyces, or both, leading to • Papillary blunting • Marked calyceal deformities  In bilateral involvement: • Kidneys are not equally contracted with • Uneven scarring Microscopically: (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 (Pink‐thyroidization(resemble thyroid)) • Glomeruli is usually normal except late when glomerulosclerosis occur (nephron loss) Typical coarse scars of chronic pyelonephritis associated with vesicoureteral reflux. The scars are usually located at the upper or lower poles of the kidney and are associated with underlying blunted calyces. Chronic Pyelonephritis – Morphology Chronic Obstructive Pyelonephritis – Morphology 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. The severity of disease depends upon the amount of remaining functional renal parenchyma. Both lymphocytes and plasma cells are seen in this case of chronic pyelonephritis. The plasma cells are most characteristic for chronic pyelonephritis. Chronic Pyelonephritis – Morphology ??? Drug‐Induced Interstitial Nephritis  Important cause of renal injury  Acute drug‐induced tubulointerstitial nephritis (TIN)  Occurs due to adverse reaction to many drugs (2 to 40 days after exposures) • Penicillins (methicillin, ampicillin & rifampin) • Diuretics (thiazides) • Nonsteroidal anti‐inflammatory agents (NSAID) • Other drugs (phenindione, cimetidine) Drug‐Induced Interstitial Nephritis – Pathogenesis  Both type I (IgE mediated) and type IV (T‐cell mediated) hypersensitivity reactions  Analgesic Nephropathy  Phenacetin injuries cells by oxidative damage  Aspirin Inhibit PG (prostaglandins )production Inhibits its vasodilatory effects Predispose Interstitial nephritis associated with papillary necrosis Drug‐Induced Interstitial Nephritis – Morphology Microscopically Characterized by:  Interstitial inflammation  Lymphocyte & Macrophage (common)  Eosinophils and neutrophils (may present in large number )  Glomeruli are normal except NSAID  Foot process effacement & Nephrotic syndrome Analgesic Nephropathy  The Papilla characterized:  Coagulative necrosis Drug-induced interstitial nephritis, there are some scattered eosinophils, along with neutrophils and mononuclear cells in the inflamed interstitium TIN – Summary Acute Kidney Injury (AKI)  AKI is defined clinically an acute rise in serum creatinine  Classified as:  Prerenal if caused by reduced blood flow to the kidneys  Intrarenal if due to injury to the renal parenchyma  Postrenal if caused by urinary tract obstruction  Intrarenal AKI is further categorized by the portion of the kidney that is mainly injured:     Glomeruli (e.g., acute glomerulonephritis) Vessels (e.g., thrombotic microangiopathy) Tubules (e.g., ischemic acute tubular injury) Interstitium (acute tubulointerstitial nephritis)  The most common cause of intrarenal AKI is ischemic acute tubular injury Acute Tubular Injury (ATI) Clinicopathologic entity characterized by:  Morphologically: damaged tubular epithelial cells  Clinical: acute decline of renal function, with granular casts and tubular cells observed in the urine  Usually reduced GFR ‐ oliguria (less than 400 mL/daily) with concurrent elevation of serum creatinine followed by electrolyte disturbances and uremia Other Causes: 1. Severe glomerular diseases (RPGN) 2. Acute tubular injury caused by diffuse renal vascular diseases (microscopic polyangiitis & thrombotic microangiopathies) 3. Acute drug‐induced allergic interstitial nephritis Two forms: a. Toxic (variety of poisons, organic solvents & drugs) b. Ischemic (generalized or localized reduction in blood flow) Acute Tubular Injury (ATI) ATI – Pathogenesis ATI – Morphology Ischemic ATI Lesions in the straight portions of the proximal tubule and the ascending thick limbs Tubular injuries:  Attenuation of proximal tubular brush borders  Blebbing and sloughing of brush borders  Vacuolization of cells  Detachment of tubular cells from their underlying basement membranes with sloughing of cells into the urine  Presence of proteinaceous casts (distal tubules and collecting ducts) • Tamm‐Horsfall protein • Hemoglobin  Casts also contain myoglobin (crush injuries) Segmental Diffuse proximal tubular injury ATI – Morphology The interstitium  Generalized edema  Mild inflammatory infiltrate • Polymorphonuclear leukocytes • Lymphocytes • Plasma cells Toxic ATI  Similar to ischemic but: • Overt necrosis is most prominent in the proximal tubule & • The tubular basement membranes generally are spared  Epithelial regeneration (If patient survives for a week) Ischemic acute tubular necrosis: Necrosis of individual tubular epithelial cells is evident both from focal denudation of the tubular basement membrane (thick arrows) and from individual necrotic epithelial cells (thin arrows) in some tubular lumens. Casts, the debris of dead tubular epithelium, fill many tubules (C). Some enlarged, regenerative‐appearing epithelial cells are also present (arrowheads). Note the lack of significant glomerular or interstitial inflammation. Toxic acute tubular necrosis due to mercury poisoning. There is widespread necrosis of proximal tubular (P) epithelial cells, with sparing of distal and collecting tubules (D). Interstitial inflammation is minimal. ATI – Clinical Features  Rapidly rising serum creatinine, usually with decreased urine output (oliguria)  Electrolyte abnormalities, acidosis, and the signs and symptoms of uremia and fluid overload  Urinalysis may help differentiate among the three major intrinsic renal diseases that cause acute renal fail ATI – Summary ATI – Question Blue arrows: Patchy or diffuse denudation of the renal tubular cells with loss of brush border Orange arrows: flattening of the renal tubular cells due to tubular dilation Yellow arrows: intratubular cast formation Red arrow: sloughing of cells, which is responsible for the formation of granular casts Green arrow: intratubular obstruction due to the denuded epithelium and cellular debris is evident Recommended Resource  Robbin Basic Pathology (10th edition)  Chapter 14, pages 564 – 569.  Essential of Rubins Pathology (8th edition)  Chapter 22, pager 955 ‐ 963.  Robbins Atlas of Pathology Thank You