Renal Pathology

Question 1

Renal Cell Carcinoma

Answer 1

• Presentation: Hematuria, paraneoplastic syndrome, metastasis
• Triad of flank pain, palpable mass, and hematuria
• metastasize hematogenously with pronounced tendency to grow into the renal vein and inferior vena cava.
• clear cell feature characteristic
• orange-yellow, often with areas of hemorrhage, necrosis and cystic change
• clear cell from cytoplasm rich in glycogen and lipids
• Papillary: the cuboidal neoplastic cells rest on elongated fibrovascular stalks.
  
  • This tumor arises from proximal tubular epithelium cells.
• Chromophobe: consists of a mixture of granular cells and pale, transparent cells with distinct cell borders.
  
  • May arise from the intercalated cells of renal collecting ducts.
• Paraneoplastic syndrome: PTH producing hypercalcemia
  
  • HTN from excess renin
  • Erythropoietin: Polycytemia
• Genetic considerations:
  
  • Gene deletion on chromosome 3
  • Von Hippel Lindau disease

Question 2

Autosomal Dominant Polycystic Kidney Disease

Answer 2

• dominant pattern much more common than the infantile form of polycystic kidney disease (autosomal recessive).
• may not appear until adulthood, even though cystic changes are present early in life.
• Possible presentations of ADPKD include hematuria, flank mass, hypertension and renal failure. Some asymptomatic
• cysts are lined by a flattened epitheliu
• association w/ berry aneurysm of cerebral arteries (15% cases)

Question 3

Autosomal Recessive Polycystic Kidney Disease

Answer 3

• Infantile form
• Multiple cysts evident at birth
• Severe cases may present with fetal demise and Potter facies.
• Less severe cases may be diagnosed in infancy w/ renal failure
• Cylindrical dilatation of collecting tubules, resulting in elongate channels at right angles to cortical surface
  
  • radial or “sunburst” pattern of cysts
• Cysts lined by cuboidal to flattened epithelium reminiscent of collecting duct epithelium.
• Normal fetal-appearing glomeruli just beneath renal capsule
• Potter sequence, secondary to oligohydramnios
  
  • decreased amount of amniotic fluid
  • characterized by abnormal facies, bowing of legs, broad spade-like hands, abundant loose skin, growth retardation and pulmonary hypoplasia.
  • ARPKD is a cause of decreased urine production leading to oligohydramnios.

Question 4

Urinary Tract Obstructions

Answer 4

• Obstruction may occur anywhere
  
  • tubules (e.g., myeloma)
  • pelvis (e.g., staghorn calculus)
  • ureters to the bladder to the urethra (e.g., prostate).
• Obstruction may be intrinsic (stones, clots, tumor) or extrinsic causing compression (tumors, fibrosis).
• Acute ureteral obstruction by a stone is intensely painful.
  
  • 70% of stones are calcium oxalate and visible on plain x-ray.
  • Predisposing: hypercalcemia, idiopathic hypercalciuria, high vitamin C intake and hyperoxaluria.
• Renal function is usually not impaired unless the condition is chronic, the obstruction is at the level of the urethra affecting both kidneys or the patient has only one kidney.
• Elevated creatinines will decrease once the obstruction is relieved in cases of prostate hyperplasia.
• Interstitial infiltrates composed of mononuclear cells
• glomerulosclerosis
• “thyroidization” of the tubules.
• Bilateral hydronephrosis.
• Renal colic

Question 5

Renal Failure

Answer 5

• etiology may be prerenal, postrenal or renal.
• Acute tubular necrosis is an example of renal azotemia.
• may be oliguria with urine output <100 cc in 24 hours.
• In ATN, proteinuria, granular casts and low urine osmolality
• kidneys swollen w/ congestion of the medulla & pallor of cortex
• The glomeruli may be normal, congested or contain a few fibrin thrombi.
• More often, bloodless & collapsed making Bowman’s space appear larger.
• Interstitium increased by edema but few inflammatory cells are found.
• The cells lining the proximal tubules become flattened and lose the surface microvilli.
• Individual cell death occurs with cells sloughed into the lumen forming casts.
• The tubules appear dilated and are difficult to distinguish from distal tubules.
• In the resolving phase, replicating cells line the tubules and mitoses can be seen.

Question 6

Chronic Pyelonephritis

Answer 6

• CPN one of the entities leading to end-stage renal disease
  
  • Others: nephrosclerosis and glomerulosclerosis.
• nephrosclerosis is secondary to hypertension
  
  • kidneys diffusely shrunken with an irregular granular surface.
• Glomerulosclerosis (sclerotic, nonfunctional glomeruli)
  
  • progression of the different types of glomerulonephritis
  • secondary to diabetes.
• Causes: chronic urinary tract obstruction and repeated bouts of acute inflammation
• Histology:
  1. Interstitial and periglomerular fibrosis.
  2. Interstitial chronic inflammatory infiltrate.
  3. Thyroidization of tubules.
  4. Glomerulosclerosis.
  5. Hyaline arteriolosclerosis

Question 7

post-streptococcal glomerulonephritis

Answer 7

• GAS induced hypersensitivity
• Acute proliferative glomerulonephritis (nephritis)
• All glomeruli are hypercellular to the same degree. (bloodless)
• hypercellularity due to mesangial cells, endothelial cell proliferation and to infiltration of WBCs.
• Many WBCs present in the glomerular capillary loops.
• WBCs in urinary space w/ RBCs and proteinaceous material.
• Many RBC and RBC casts are present in the tubules.
• Interstitial edema is apparent.
• Azotemia
• Subepithelial electron dense humps
• Lumpy bumpy Immunofluorescence
• Granular deposits of IgM, IgG, and C3 along the BM
• Lab findings: RBC/WBC casts, azotemia, decreased serum C3, increased antistreptococcal antibodies

Question 8

Goodpasture Syndrome

Answer 8

• Caused by antiglomerular basement membrane antibodies
• glomerular crescents of cells derived from the parietal epithelium, that compress the glomerular tufts.
• Some fibrous crescents
• Variable leukocytic infiltrates and RBCs are present in the Bowman’s space and tubules.
• Characteristic wrinkling of glomerular basement membrane with focal disruptions in its continuity
• No electron-dense deposits are seen.
• Diffuse linear staining of the basement membrane along the capillary walls with IgG antibody is characteristic.
  
  • From antiglomerular basement membrane antibodies
• Presentation: nephritic syndrome
  
  • Pneumonitis with hemoptysis
  • RPGN crescentic morphology w. linear Immunofluorescence
• Peak incidence in men in mid 20s
• Treat w/ plasmapheresis combined with corticosteroids and cytotoxic agents

Question 9

Minimal Change Disease

Answer 9

-glomeruli are essentially normal by light microscopic
-some granularity in the cells of the proximal convoluted tubules due to lipid resorption droplets in the cytoplasm.
*reabsorption of lipoproteins leaking through diseased glomeruli
-visceral epithelial cell foot processes are completely effaced
*due to retraction into the cell bodies
*replaced by a rim of cytoplasm.
-surface microvilli are present on the surface of the epithelial cells.
*There are often large cytoplasmic lipid vacuoles.
-Edema, hypercholesterolemia, proteinuria,
-Genetic problem w/ protein nephrin
-

Question 10

Membranous Glomerulonephritis

Answer 10

• Immune complex disease of unknown etiology
• Major cause of nephrotic syndrome
• Incidence highest in teens and young adults
• Should be suspected if nephrotic syndrome w/ azotemia
• glomeruli enlarged w/ mesangial matrix increase & normal cellularity.
• peripheral capillary walls are diffusely thickened,
  
  • stiffness to the appearance of the glomerular capillary loops
• Silver methenamine stain (stains BM black)
  
  • reveals a “spike and dome” appearance in the capillary loops.
  • due to projection of thickened glomerular BM b/t large deposits
• Irregular deposits found on the subepithelial aspects of the BM of the capillary wall.
  
  • B/t the deposits are extensions of the BM (“spikes”)
• Foot process effacement in relation to the presence of deposits
• Granular deposits of IgG and usually C3 along the glomerular capillary basement membrane are characteristic.
• Seen in 10% of patients w/ SLE
• Associated w. HepB, Syphilis, malaria, drugs, and malignancy

Question 11

IgA Nephropathy: Berger Disease

Answer 11

• Presents w/ benign recurrent hematuria following infection
• Extremely Common entity; Male predominant
• Component of Henoch-Schonlein Disease
• Defined by IgA depositions in the mesangium
• Mild expansion of mesangial areas
  
  • increase in mesangial matrix and mesangial cells
• Some glomeruli have increase in matrix and cellularity.
• Mesangial droplets seen w/ periodic acid-Schiff or Masson’s trichrome stain.
• Deposition of IgA often with C3 in the mesangium and less frequently in the perimesangial- subendothelial areas.
• up to 25-50% of patients actually progress to end- stage renal failure.

Question 12

Diabetic glomerulosclerosis

Answer 12

• Glomeruli are normo-cellular.
• Diffuse thickening of the glomerular capillary wall and increase in mesangial matrix are characteristic of diffuse type
• glomeruli w/ acellular sclerotic nodules in mesangial regions consisting of mesangial matrix characteristic of nodular type
• arterioles show marked hyaline arteriosclerosis
  
  • Both afferent and efferent arterioles are involved.
• thickening of the basement membrane
• sclerotic appear as matrix compressing the mesangial cells.
• Immunofluorescence: delicate diffuse linear staining
  
  • mimicking that of anti-GBM disease
  • antibodies to IgG or albumin.
  • Complement is usually absent.
• nonenzymatic glycosylation of basement membrane proteins
  
  • results in increased albumin binding and protease-resistant cross- linking of collagen may be partially responsible