Renal Pathology: Cystic & Vascular Disorders, Urinary Tract Obstruction PDF

Pathology RENAL CYSTIC DISORDERS RENAL VASCULAR DISORDERS URINARY TRACT OBSTRUCTION  RENAL CYSTIC DISORDERS RENAL VASCULAR DISORDERS URINARY TRACT OBSTRUCTION Axel Baez-Torres M.D., FCAP Associate Professor Pathology Department Ponce Health Sciences University CYSTIC...

Pathology RENAL CYSTIC DISORDERS RENAL VASCULAR DISORDERS URINARY TRACT OBSTRUCTION  RENAL CYSTIC DISORDERS RENAL VASCULAR DISORDERS URINARY TRACT OBSTRUCTION Axel Baez-Torres M.D., FCAP Associate Professor Pathology Department Ponce Health Sciences University CYSTIC DISEASES OF THE KIDNEY CYSTIC DISEASES OF THE KIDNEY Heterogeneous group comprising hereditary, developmental but not hereditary and acquired disorders: Common disorders that often represent diagnostic problems Some forms may cause chronic renal failure They can occasionally be confused with malignant tumors RENAL DYSPLASIA Renal dysplasia is a sporadic disorder that can be unilateral, bilateral and is often cystic. Unilateral multicystic renal dysplasia is the most common cause of a renal mass in childhood Bilateral lesions may present in utero or shortly after birth with oligohydramnios and Potter’s syndrome RENAL DYSPLASIA Macroscopic: Dysplastic kidneys may be unilateral or bilateral, large or small, reniform or irregular, and solid or cystic RENAL DYSPLASIA Microscopic: Disorganized overall architecture. Presence of primitive ducts, aberrant glomeruli, cysts and immature cartilage and mesenchymal tissue RENAL DYSPLASIA The clinical outlook depends on the extent of dysplasia if bilateral, and the function of the contralateral kidney if unilateral AUTOSOMAL DOMINANT POLYCYSTIC DISEASE (ADPKD) The most common cystic renal disease with an estimated frequency between 1:500 and 1:1,000 and a nearly complete penetrance by the 5th decade There is some genetic heterogeneity but nearly 85% of cases in Caucasians are associated with a defect in chromosome 16p causing a mutation of the PKD-1 gene which encodes a protein named polycistin-1. The remaining 15% have mutations in PKD-2 gene (chr. 4q) which encodes polycystin-2 ADPKD Most patients present in the third to fourth decade with dull abdominal pain and bilaterally palpable kidneys. Hypertension may be the initial manifestation. Flank pain may be due to cyst hemorrhage, cyst infection, and renal stones. ADPKD Extrarenal manifestations include polycystic liver disease (75%), mitral valve prolapse (25%), pancreatic cysts (10%) and intracraneal berry aneurysms (10-20%) ADPKD Renal failure occurs in 50% of patients an average of 10 years after clinical detection Patients with ADPKD account for 10% of patients in the U.S. on dialysis and 6% of renal transplants ADPKD Macroscopic: The kidneys are large, ranging from 250-4000 gms and usually maintain a somewhat reniform shape Variable numbers of spherical, unilocular cysts are present within the cortex and medulla The calyces, pelvis and papillae are often greatly distorted ADPKD Microscopic: The cysts arise from the tubules throughout the nephron and therefore have variable lining epithelia AUTOSOMAL RECESSIVE POLYCYSTIC DISEASE (ARPKD) Occurs in1:6,000 to 1:14,000 live births and has a 2:1 female predominance Genetically homogeneous disease associated with a defect in chromosome 6p causing mutations of the PKHD-1 gene which encodes a protein named fibrocystin which probably acts as a cell surface receptor with a role in collecting duct and biliary differentiation ARPKD Many affected newborns have severe disease with a grossly enlarged abdomen, kidneys and signs of oligohydrammnios. In the first days of life, these neonates develop fatal respiratory distress and congestive heat failure ARPKD Older children and adults show a variable course with approximately 30% developing chronic renal failure Those who survive infancy may develop congenital hepatic fibrosis with associated portal hypertension and splenomegaly ARPKD Macroscopic: The renal capsule is smooth with numerous small cysts On section the cysts extends radially through the cortex ARPKD Microscopic: The cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting tubules NEPHRONOPHTISIS (MEDULLARY CYSTIC DISEASE) Usually presents as an autosomal recessive hereditary disease in which cysts arise at the corticomedullary junction Various genotypic forms exist, associated to mutations in proteins, such as nephrocystin, that are present in the primary cilia or basal bodies. Nephronopthisis Familial juvenile nephronopthisis is the most common variant accounting for 40-50% of cases. The NPHP1-NPH11 genes are mutated in the different forms of this variant. The disease present as a renal tubular defect with impaired renal concentrating capacity, polyuria and polydipsia. In addition, extrarenal abnormalities such as hepatic fibrosis and retinal degeneration are occasionally present in syndromic variants. Nephronopthisis As a group, this complex is now thought to be the most common genetic cause of end-stage renal disease in children and young adults. NEPHRONOPTHISIS Macroscopic: Symmetrically small kidneys with numerous cysts near the corticomedullary junction NEPHRONOPTHISIS Microscopic: Severe, widespread tubular atrophy and interstitial fibrosis Cysts lined by cuboidal to flattened epithelium MEDULLARY SPONGE KIDNEY Characterized by dilatation of collecting ducts in the renal pyramids, usually without significant compromise of renal function The majority of cases appear to be sporadic Occasional cases are detected as a result of complications which can include hematuria, infections and nephrolithiasis ACQUIRED RENAL CYSTIC DISEASE Most common in patients undergoing long-term dialysis The majority of cases are asymptomatic Painful cyst hemorrhage, retroperitoneal hemorrhage or infection can occur The most serious complication of acquired renal cystic disease is the development of renal cell carcinoma over the years (100-fold increased risk). SIMPLE CYSTS Common incidental findings at autopsy or on CT scans of the abdomen May be solitary or multiple, unilateral or bilateral Cysts may be found anywhere in the kidney, including the cortex and medulla SIMPLE CYSTS The majority of cysts are asymptomatic and not associated with significant complications The major significance of the discovery of simple renal cysts in the need to exclude a renal neoplasm RENAL VASCULAR DISORDERS  VASCULAR DISEASES OF KIDNEY The kidneys receive approximately 25% of the cardiac output Therefore, they are greatly affected by diseases of the blood vessels  VACULAR DISEASES OF KIDNEY Ischemic renal disease: significant reduction in glomerular filtration rate because of hemodynamically significant renovascular occlusive disease affecting the entire functioning renal parenchyma  VASCULAR DISEASES OF KIDNEY Diseases involving the larger arteries include atherosclerosis, thrombosis and thromboembolism Smaller arteries and arterioles are most often affected by hypertension and thromboembolism  VASCULAR DISEASES OF KIDNEY Arteries of the kidneys are usually considered to be end- organ type, with no effective collateral circulation Thus, sudden occlusion of arteries usually results in infarction  VASCULAR DISEASES OF KIDNEY Renal ischemia caused by stenosis of main renal arteries or narrowing of intrarenal arteries activates the renin- angiotensin – aldosterone system resulting in a pathologic increase in blood pressure  ESSENTIAL HYPERTENSION The most common cause of systemic hypertension Divided in mild to moderate (benign) hypertension and severe (malignant) hypertension  ESSENTIAL HYPERTENSION Benign hypertension is major risk factor for cerebrovascular accidents, coronary artery disease, myocardial infarction and renal disease Malignant hypertension usually presents with pressure over 190/120 but is best defined by associated clinical conditions including papilledema, congestive heart failure, stroke, encephalopathy and renal insufficiency  BENIGN HYPERTENSION Normal or moderately reduced in size and weight kidneys Granular capsular surface Thin cortex Ischemic nephropathy changes may be present Arteries demonstrate intimal fibroplasia and reduplication of internal elastic lamina Hyaline arteriolosclerosis characterized by homogeneous eosinophilic material replacing the media of arterioles  MALIGNANT HYPERTENSION Cortical surface petechial hemorrhages Ischemic nephropathy changes may be present Arterial intimal fibroplasia Fibrinoid necrosis of arterioles with or without necrotizing arteriolitis Hyperplastic arteriolitis (onion-skin lesion) of interlobular arterioles and larger arterioles  RENAL ARTERY STENOSIS Significant cause of secondary hypertension Atherosclerosis is the most common cause of occlusion of large renal arteries. The most affected group are older men. Occlusion usually involve the proximal renal arteries. 50% of cases origin from the aorta. Bilateral disease is present in up to 60% of cases  RENAL ARTERY STENOSIS Less common causes include thromboembolic disease, thrombosis of main renal arteries, vasculitis and fibromuscular dysplasia  FIBROMUSCULAR DYSPLASIA Occurs more commonly in young women Usually causes concentric narrowing of the artery Alternating constrictions and aneurysmal dilatations may be present Medial fibroplasia is the most common variant; is most often bilateral and seldom causes total arterial occlusion  RENAL ARTERY STENOSIS Clinical course Consequences of occlusion depends on the size and number of vessels involved, rate of closure, presence or absence of collateral circulation and whether occlusion is unilateral or bilateral  RENAL ARTERY STENOSIS Clinical course Sudden occlusion usually results in infarction Gradual narrowing result in ischemic nephropathy. Once ischemic disease has developed it tends to progress rapidly, approximately half of patients have evidence of progression within two years  RENAL ARTERY STENOSIS Treatment Renal artery stenosis, if detected early, may potentially be reversed by angioplasty or bypass graft In long-standing unilateral renal artery stenosis, correction of the stenosis may not relieve the hypertension  TROMBOTIC MICROANGIOPATHIES Hemolytic uremic syndrome (HUS) and Thrombotic thrombocytopenic purpura (TTP) Closely related entities with virtually identical renal pathology It may not always be possible to distinguish the two conditions  THROMBOTIC MICROANGIOPATHIES Characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure Disease is related to endothelial injury and the subsequent activation of the coagulation system  HEMOLYTIC UREMIC SYNDROME Classic form occurs mainly in young children and is associated with prodromal diarrhea Most classic form cases are associated with infection from verotoxin- producing strains of E. coli (especially 0157:H7 and more recently associated with 0104.H4)  HEMOLYTIC UREMIC SYNDROME Diarrhea-negative disease can be further classified as sporadic or familial The sporadic form can be associated with diverse acquired causes of endotelial injury and other conditions such as complications of pregnancy, SLE, HIV and a variety of drugs The familial form has been linked to mutations in complement regulatory protein factor H  THROMBOTIC THROMBOCYTOPENIC PURPURA Disease occur most commonly in women in the fourth and fifth decades Most patients presents with neurologic symptoms (seizures, aphasia, altered levels of consciousness) Severe renal damage is uncommon  THROMBOTIC THROMBOCYTOPENIC PURPURA The disease has been linked to inherited or acquired deficiencies of the metalloprotease ADAMTS-13, which is responsible for the breakdown of large Von Willebrand factor multimers The absence of ADAMTS-13 results in an excess of VWF multimers, which are prothrombotic as they promote spontaneous activation of platelets.  THROMBOTIC MICROANGIOPATHIES Treatment and clinical course In most of classic HUS cases, the renal function is recovered if renal failure is treated adequately with dialysis. Plasma exchange is the single most important treatment for TTP, providing a survival rate of over 80%  CHOLESTEROL EMBOLI The kidneys are the most common organs involved by cholesterol embolization Usually occur in older people with atherosclerosis of the thoracic or upper abdominal aorta Onset frequently occur one to several weeks after angiography, cardiovascular surgery or another precipitating event  CHOLESTEROL EMBOLI The emboli affects the smaller arteries and arterioles Renal manifestations include increased serum BUN and creatinine Renal involvement is variable in severity but may be progressive and result is severe renal failure requiring dialysis  RENAL CORTICAL NECROSIS Uncommon cause of renal failure which occur in the setting of severe circulatory failure The condition is frequently bilateral The most common causes are obstetric complications such as placental abruption or eclampsia  RENAL CORTICAL NECROSIS The usual clinical finding is acute renal failure The general histologic appearance resemble those of renal infarction With hemodialysis a significant number of patients survive but are left with considerable residual renal insufficiency  RENAL INFARCTION Major cause is related to embolism, usually from left side of heart Many renal infarcts are clinically silent The severity of disease depends on the size of the vessel affected and the resulting amount of renal tissue that is infarcted URINARY TRACT OBSTRUCTION UROLITHIASIS  URINARY TRACT OBSTRUCTION The causes of urinary tract obstruction are multiple Among intrinsic causes nephrolithiasis, sloughed renal papilla, strictures and cancer are the most common Among extrinsic causes carcinoma of the uterine cervix or endometrium, prostatic hyperplasia, retroperitoneal fibrosis and retroperitoneal tumors are the most common  URINARY TRACT OBSTRUCTION Urinary tract obstruction is more common in males than females in childhood; the most common causes include ureteropelvic or vesicoureteral obstruction Between childhood and age 60 is more common in females; the most common cause is a gynecologic tumor After age 60 is again higher in men, primarily because of prostatic disease  URINARY TRACT OBSTRUCTION Pathophysiology The pathophysiologic mechanisms by which urinary tract obstruction damages the kidney include increased pressure into the medulla, intrarenal reflux of urine and direct pressure on blood vessels within the medulla  URINARY TRACT OBSTRUCTION Clinical features The clinical picture of urinary tract obstruction is highly variable; bilateral partial obstruction may present with loss of ability to concentrate urine whereas sudden complete obstruction presents with acute renal failure  URINARY TRACT OBSTRUCTION Treatment and clinical course Treatment depends on the primary condition causing the obstruction The most important factor in determining the degree of recovery is the duration of obstruction  UROLITHIASIS The formation of renal calculi depends on a balance of factors: 1. Concentration of the specific component (supersaturation) 2. Presence of nucleating factors such as epithelial cells, debris or casts 3. Deficiency of stone inhibitors such as nephrocalcin, the Tamm-Horsfal protein or citrate  RENAL CALCULI Type Proportion Calcium oxalate 75% Struvite 10-15% Uric acid 5-6% Cystine 1% Other 15%  UROLITHIASIS Calcium oxalate stones Vast majority of renal calculi Over half calculi are associated with hypercalciuria without hypercalcemia Approximately one fifth are associated with hyperuricosuria  UROLITHIASIS Struvite stones Magnesium ammonium phosphate stones Strongly associated with infection with urea-splitting bacteria, most often Proteus species The resultant alkaline urine causes the precipitation of magnesium ammonium phosphate salts. Large staghorn calculi are almost always associated with this type of stone  UROLITHIASIS Uric acid stones Majority of patients have neither hyperuricemia or hyperuricosuria, but commonly seen in individuals with hyperuricemia (gout, diseases involving rapid cell turnover such as the leukemias). Stone formation in this patients is believed to be due to a tendency to excrete urine with pH below 5.5 as uric acid is insoluble in acidic urine  UROLITHIASIS Clinical features Renal colic syndrome manifested by flank/groin excruciating pain; nausea and vomiting are frequent Calculi may be painless if they remain in the pelvis Hematuria is a frequent manifestation  UROLITHIASIS Clinical course Smaller stones are more likely to cause complications because they are free to pass into the ureter Calculi predispose to infection due to obstruction and trauma  UROLITHIASIS Treatment Stones less than 5mm are likely to pass spontaneously Stones less than 2cm can often be treated with lithotripsy Larger stones may require nephrolithotomy Figures and tables in this presentations are from Robbins Pathology 10th edition.