Renal: 11-12pmScribe: Strudwick Louis Tutwiler

Friday, May 15, 2009Proof: Ryan O’Neill

Dr. HameedRenal PathologyPage1 of 7

  1. Tubulointerstitial Diseases [S51-52]
  2. Pyelonephritis – infection of the pelvis
  3. Acute
  4. Chronic
  5. Interstitial nephritis – common problem; might encounter
  6. Acute drug-induced interstitial nephritis
  7. Analgesic nephropathy – complication of analgesic administered for pain
  8. Acute tubular necrosis – major cause of acute renal failure
  9. Acute Pyelonephritis [S53-56]
  10. Bacterial infection of kidney and renal pelvis - bacterial in origin
  11. Common pathogens
  12. Enteric gram-negative rods – gives ascending infection from urethra to kidney (fecal or parasites)
  13. Escherichia coli most common
  14. Proteus, Klebsiella, Enterobacter, Pseudomonas
  15. Clinical presentation
  16. Flank (costovertebral angle) pain of sudden onset
  17. Fever, chills, malaise (feel and look very sick)
  18. Symptoms of bladder irritation (dysuria = painful urination, frequency = urination at increased intervals, urgency = strong sudden desire to urinate)
  19. Urinalysis shows bacteriuria, pyuria (pus), and WBC casts (as opposed to RBC casts in Nephritic Syndrome)
  20. Pathogenesis
  21. Two routes of infection – 2 mechanisms
  22. Ascending (most common) – from urethra to kidney; most common with gram negative from gut
  23. Hematogenous – from arterial system; systemic spread; kidney biopsy will be determined to further identify systemic diseases.
  24. Predisposing factors
  25. Instrumentation – introduction of organisms (bacteria) into urinary tract (presently few are there – urine is definitely sterile in kidney)
  26. Urinary obstruction – body clears infection by continuous flow of urine. Obstruction allows overgrowth of bacteria.
  27. Vesicoureteral reflux – once urine reaches bladder, it should not return backwards. With this reflux, urine goes back up.
  28. Female gender – have shorter urethra that predisposes them to more infections, especially Pyelonephritis. Females have shorter urethra so bacteria introduced during intercourse.
  29. Similar for VUR
  30. Pictures: Characteristic findings are suppurative necrosis and abscess formation in renal parenchyma. Can see WBC infiltrate in urine with the WBC casts will sit inside tubules.
  31. Complications
  32. Sepsis and septicemia (pts can die if left untreated)
  33. Pyonephrosis – pus within the collection system
  34. Expansion of renal pelvis, calyces, and ureter by pus
  35. Occurs with obstruction; pus compresses the kidney
  36. Papillary necrosis
  37. Ischemic and suppurative necrosis of tips of renal pyramids
  38. Common in diabetics and with interstitial nephritis from analgesic abuse
  39. Patients with significant urinary tract obstruction causing infections
  40. Treatment
  41. Antibiotics and relief of obstruction – should always relieve obstruction and drain pus
  42. depends on cause; correction of anatomic obstruction, if present
  43. Chronic Pyelonephritis [S57]
  44. Chronic interstitial inflammation with gradual scarring that can result in chronic renal failure
  45. Recurrent low grade infection due to obstruction or vesicoureteral reflux
  46. Recurrent or long-standing pyelonephritis
  47. Renal pelvis and kidney become progressively scarred
  48. Results in chronic renal failure - accounts for 20% of end-stage renal disease
  49. Gross findings
  50. Scarring and deformity of pelvis or calyces
  51. Can have shrunken kidney or with hydronephrosis (have enlarged kidney)
  1. Microscopic findings
  2. Chronic inflammation in interstitial
  3. Interstitial fibrosis with healing – increased fibrous tissue
  4. Dilatation of tubules with atrophy of epithelium (“Thyroidization”) – looks like thyroid glands
  5. Glomeruli usually normal, but can develop focal segmental glomerulosclerosis (at start, they are normal though)
  1. Ureteric reflux [S58]
  2. Normal insertion of ureter into bladder has this oblique pathway through the wall. When bladder is expanded, ureter is closed preventing backflow of urine.
  3. In reflex, it has a more perpendicular circumstance, so with increased pressure urine will backflow into kidneys. If the urine is infected, it can cause pyelonephritis.
  4. Chronic Pyelonephritis [S59-60]
  5. The blunt injury occurs at both poles of the kidney. Have blunting of calyx and overlying scaring.
  6. Right shows blunting with scarring in pyelonephritis.
  7. “Thyroidization.” This is not a normal pattern of histology of kidney. This is a low power showing fibrosis of the tubules.
  8. Acute drug-induced interstitial nephritis [S61-62]
  9. Due to
  10. NSAIDs
  11. Antibiotics such as methicillin, ampicillin, rifampin – unexpected side effect
  12. Diuretics such as thiazides
  13. Others such as cimetidine
  14. Occurs approximately 2 weeks after drug exposure – systemic illness
  15. Fever and skin rash
  16. Eosinophilia – a lot of eosinophils will be seen in peripheral blood and in kidneys
  17. Acute renal failure with oliguria in 50% of cases
  18. Urinalysis
  19. Hematuria and proteinuria with eosinophils in urine
  20. Prognosis
  21. Reversible upon removal of offending agent
  22. Pathology
  23. Chronic inflammation in interstitial and tubules
  24. Interstitial edema with infiltrate of lymphocytes, macrophages, neutrophils and eosinophils (reddish cells)
  25. Thought to represent immune-mediated response to drug
  26. If the patient quits taking the drug, everything will resolve. The problem is many of these patients come in with some form of renal failure already.
  27. Hapten=binds to some component of tubular epithelial cells and becomes immunogenic
  28. Analgesic nephropathy [S63]
  29. Interstitial nephritis associated with renal papillary necrosis
  30. Usually due to consumption of combinations of analgesics (NSAIDS and phyastitine? are most common and classic culprits)
  31. Gross
  32. Yellow-brown necrotic papillae surrounded by hyperuremic edges (similar to a myocardial infarction)
  33. May slough and drop into pelvis
  34. Patients that are more likely to develop are diabetics and patients with sickle cell disease.
  35. Microscopic
  36. Coagulative necrosis
  37. Acute Tubular Necrosis [S64-66]
  38. Clinicopathologic syndrome
  39. Acute renal failure (ARF) – most common cause of ARF
  40. Histology: destruction of tubular epithelium – hallmark for identification
  41. Most common cause of ARF and is secondary to: ischemic or toxic mechanism
  42. Ischemia
  43. Hypotension and shock – kidney will try to conserve water and electrolytes inducing vascular changes in kidney. Eventually get ischemia and necrosis of tubules.
  1. Nephrotoxic substances
  2. Heavy metals – usually accidental
  3. Organic solvents
  4. Drugs
  5. Radiographic contrast agents – why patients with Acute Tubular Necrosis cannot get a contrast enhanced CT scan (could induced ARF). This would be a contraindication for these patients.
  1. Dilated prominent tubules with eosinophils; tubules are very active in transport.
  2. Flattened, atrophic epithelium – can eventually get regeneration of epithelium with proper management of acute tubular necrosis.
  3. Interstitial inflammation
  4. After 1st week, regeneration of tubular epithelial cells
  5. Pathology
  6. Tubular injury, persistent and severe disturbances in blood flow
  7. Necrosis and sloughing of tubular epithelium
  8. Clinical course
  9. Initiating event predominates clinical picture first 36 to 48 hours. Ex. 2-3 days after patient is admitted to a hospital with acute myocardial infarction, ARF develops.
  10. Maintenance phase (2-6 days)
  11. ARF with oliguria persisting up to 3 weeks
  12. Requires dialysis and other supportive therapy to prevent uremia
  13. Recovery phase
  14. 90% to 95% recover
  15. Return of normal urine output – the first thing to return is filtration (polyuria = high urine outflow), and the last thing to return to normal is concentration abilities.
  16. Increased risk of infection, electrolyte imbalances
  1. Hypertensive Nephropathy [S67]
  2. Kidney is damaged by hypertension, as are many organs.
  3. Two main types: Benign or Malignant
  4. Benign Nephrosclerosis [S68-69]
  5. Not really benign because it can still cause kidney damage, but is it is benign in comparison to malignant nephrosclerosis.
  6. Associated with chronic hypertension resulting in slow loss of kidney function
  7. Rarely causes severe renal damage
  8. Usually some degree of functional impairment (decrease in GFR and/or mild proteinuria)
  9. Gross findings
  10. Symmetrically atrophic kidneys with finely granular surface
  11. Diffused process with the entire kidney being shrunken
  12. Histology
  13. Hyaline thickening of small arteries and arterioles (hyaline arteriolosclerosis)
  14. Eventually, loss of function and atrophy of tubules and glomeruli
  15. Associated with benign hypertension
  16. Progresses over years to decades (>95% of patients)
  17. GFR slowly decreases
  18. Patients usually die from cardiovascular lesions before renal failure ensues
  19. Left Picture: small shrunken granular surface without focal lesions
  20. Right Picture: can see hyaline arteriolosclerosis – notice marked thickening of vascular wall.
  21. Malignant Nephrosclerosis [S70-71]
  22. More significant than benign nephrosclerosis
  23. Malignant hypertension
  24. Occurs in ~5% of patients with HTN and characterized by diastolic BP > 120 mm Hg associated with headache, vomiting and other S&S. Brain function is lowered.
  25. Clinical course
  26. Medical emergency! Patients might stroke half their brain if left untreated.
  27. Requires aggressive antihypertensive therapy to prevent irreversible damage
  28. Histological findings: Either two types of changes:
  29. Fibrinoid necrosis – similar to hyaline arteriolosclerosis except it is necrotic. It is also associated with necrosis inside glomerulus because of afferent and efferent vessels.
  30. Hyperplastic arteriolosclerosis – onion skinning. Progressive thickening of arterial walls
  31. Fibrinoid Necrosis (left picture)
  32. Hyperplastic Arteriolosclerosis (right picture)
  33. <5% of patients with hypertension - rapidly progressive with an unclear etiology
  34. Cystic Diseases of Kidneys [S72]
  35. Acquired cysts with chronic renal failure, which results in a systemic change are Nonspecific
  36. Specific cystic diseases are congenital ones. There are two main types: Autosomal dominant or recessive
  37. Autosomal Dominant (Adult) Polycystic Kidney Disease (ADPKD) [S73-74]
  38. Usually occurs in adulthood
  39. Multiple bilateral (involve both kidneys) expanding cysts that destroy the intervening renal parenchyma
  40. Occurs in 1/1000 (not uncommon) and accounts for 10% of cases of CRF
  41. Inheritance
  42. APKD-1 (90%) on ch16
  43. APKD-2 (10%) on ch4
  44. Clinical course
  45. Asymptomatic until 4th decade
  46. Initial symptoms include flank pain and hematuria
  47. Associated lesions
  48. Berry aneurysms (10 to 30%) – sack dilations of blood vessels within brain vascular; might rupture causing death
  49. Liver cysts (30%)
  50. Course variable, usually slowly progressive – present with HTN and renal failure later in life
  51. ESRD usually by age 50
  52. Treated by transplantation
  53. Autosomal Recessive (Childhood) Polycystic Kidney Disease [S75]
  54. Usually occurs in childhood
  55. Relative size of the kidney is the same
  56. Numerous bilateral small “sponge-like” cysts in the cortex and medulla
  57. Associated with multiple epithelium-lined cysts in the liver and bile duct proliferation
  58. Patients surviving infancy after chronic renal failure develop congenital hepatic fibrosis
  59. This usually will led to chronic renal failure requiring transplantation.
  60. Disorders of the Collecting System [S76]
  61. Ex. Pelvis. Processes that occur are the same that occur in the bladder and urethra. Tumors that occur in pelvis are the same that occur in bladder. Same kind of structure and epithelial lining
  62. Urolithiasis [S77]
  63. “Kidney stones” – or renal stones; most common disorder; can occur anywhere from pelvis to bladder.
  64. Calculi occur most often in kidney but can arise anywhere within collecting system
  65. Common disorder
  66. Symptomatic calculi more common in males
  67. Familial tendency
  68. Presentation depends on size and location of stone; also depends on how quickly obstruction occurs.
  69. Asymptomatic = slowly developing stone
  70. Severe, paroxysmal flank pain (ureteral colic) = acute obstruction with pain in characterized as between a toothache and childbirth.
  71. Hematuria due to stone irritating the wall
  72. Infection secondary to obstruction from large calculi
  73. Etiology:
  74. Increased concentration of stone constituents in urine (supersaturation)
  75. Composition depends on underlying etiology
  76. Metabolic abnormalities
  77. Stone Composition [S78]
  78. Do not need to know all the causes listed here!
  79. Calcium oxalate / phosphate (75%) – most common type; increased Ca or phosphate in urine
  80. Idiopathic hypercalciuria
  81. Hypercalcemia
  82. Hyperuricosuria
  83. Hyperoxaluria
  84. In hyperparathyroidism, parathyroid is very active resulting in Hypercalcemia.
  85. Need a good ion balance.
  1. Magnesium ammonium phosphate (15%)
  2. Struvite stones
  3. Persistently alkaline urine due to UTI (Proteus vulgaris)– associated with frequent infections (important to remember)
  4. “Staghorn calculi” – very large and can fill up entire pelvis
  5. Uric acid (6%) - rare
  6. Gout
  7. Cystine (1-2%) - rare
  8. Genetic defect in renal transport of amino acids
  9. Idiopathic hypercalciuria may be due to increased GI absorption or decrease renal reabsorption.
  10. Hyperuricosuria and hyperoxaluria provide nidus for stone formation.
  1. Picture [S79]
  2. Staghorn calculus filling kidney
  3. Hydronephrosis [S80-81]
  4. Dilatation of renal pelvis and calyces with secondary atrophy of renal parenchyma
  5. Can have hydronephrosis with or without hydroureterosis (ureter is also dilated)
  6. Caused by obstruction of urinary flow at any level of urinary tract
  7. Causes
  8. Intrinsic (tumor within urethra) vs. extrinsic (pelvic lymph node or ovarian tumor)
  9. Congenital (structures along urethra) vs. acquired (like most causes)
  10. Unilateral vs. bilateral – main distinction
  11. Presentation:
  12. Bilateral obstruction: Anuria, bladder distension
  13. Unilateral obstruction: May remain silent, enlarged kidney on examination
  14. Back pressure on kidney
  15. Bilateral
  16. Obstruction below level of ureters (i.e. at bladder neck, prostate and urethra)
  17. Anuria if complete obstruction
  18. Leads to renal failure if not corrected
  19. Unilateral
  20. Obstruction at level of ureter or above (before bladder)
  21. May remain silent for a long time if remaining kidney functioning properly
  22. Gross Picture – pelvis is markedly dilated. You can still see the cortex and medullar junction, but this will eventually fade away.
  23. Acute Bilateral Obstruction – loss of urine with ACR; do not have time for hydronephrosis to develop. Chronic Bilateral Obstruction – can have Hydronephrosis with gradual loss of function. Acute will be painful. Audio was fading out at this time.
  24. Chronic Unilateral Obstruction – painless, hydronephrosis with loss of urine from this kidney, & asymptomatic. It is a nonfunctional kidney, but patient is okay because the other kidney has taken up the workload.
  25. Etiologies are diverse:
  26. Congenital: E.g. atresia of ureter, ureteral valves
  27. Acquired: Urolithiasis tumors of the bladder and ureters, hypertrophy or carcinoma of the prostate, prostatitis, ureteritis
  28. Neoplasms [S82]
  29. Discuss a pediatric neoplasm and an adult neoplasm. Audio wentout at 34:00.
  30. Wilms’ Tumor (Nephroblastoma) [S83-84]
  31. 4th most common pediatric malignancy in US
  32. It is the 2nd most common solid neoplasm and the 1rd most common extracranial solid neoplasm. I could not understand the 1st and 2nd most common pediatric malignancy.3rd most common are brain tumors, with Wilm’s tumor as 4th.
  33. Peak incidence is two to five years
  34. 5 to 10% are bilateral – Most bilateral Wilms' Tumor is associated with a syndrome occurrence.
  35. Clinical features at presentation
  36. Abdominal mass – most common. Audio went out at 36:00.
  37. Pain
  38. Hematuria – if it involves the pelvis of the kidney.
  39. Pulmonary metastases or metastases elsewhere
  1. Occurrence
  2. Sporadic (95%) – most
  3. Familial (1-2%)
  4. Syndrome-associated (2%) – up to 50 different syndromes described with this tumor.
  5. Histological findings
  6. Recapitulates renal tissues during varying stages of nephrogenesis (during 7-8 week old fetus)
  7. Triad of components - called “Triphasic Tumor”
  8. Blastemal – undifferentiated dark cells
  9. Stromal – immature mesenchymal stromal elements
  10. Epithelial – develop out of blastemal layer; trying to form immature tubules
  1. Wilms’ Tumor: Genes involved [S85]
  2. Most common genes associated with this tumor. All of these are tumor suppressor genes.
  3. WT1 —11p13; on chromosome 11
  4. Developmentally expressed in the kidney and gonads of the developing fetus (expressed like an oncogene during development)
  5. Mutated in ~10% of patients with sporadic tumors
  6. WT2 —11p15.5; on chromosome 11
  7. WTX — Xq11.1
  8. Seen in ~30% of sporadic cases
  9. Wilms’ Tumor: Prognosis [S86]
  10. Combined use of nephrectomy and chemotherapy gives ~90% long-term survival
  11. Patients who survive have increased risk of second primary tumors (secondary malignancy)
  12. Renal Cell Carcinoma [S87]
  13. Common neoplasm; common visceral malignancy
  14. 2% of all adult cancers
  15. 80% to 90% of renal malignancies; much more common than urothelial or transitional cell carcinoma
  16. Patients typically 40 to 70, males > females
  17. Risk factors:
  18. Cigarette smoking – risk factor any cancer
  19. Hereditary
  20. Von Hippel-Lindau disease
  21. Other familial forms
  22. Adult Polycystic Kidney Disease
  23. Von Hippel-Lindau (VHL) Syndrome [S88]
  24. Autosomal dominant condition characterized by:
  25. CNS and retinal hemangioblastomas
  26. Renal cell carcinoma
  27. Pheochromocytoma – adrenal tumor
  28. Islet cell tumor of pancreas
  29. VHL gene is tumor suppressor gene on 3p25 – lost of chromosome 3
  30. Translocations of chromosome 3 in familial RCC
  31. Mutations of chromosome 3 in sporadic cases
  32. VHL gene or closely related gene on chromosome 3 likely involved in renal carcinogenesis
  33. In VHL, have germ line loss. In sporadic tumor, have loss within the tumor itself.
  34. Renal Cell Carcinoma [S89-93]
  35. Variable presentations
  36. “Classic Triad”-10%
  37. Hematuria (most common--50%) “Classic Triad”
  38. Flank pain (40%)
  39. Fever
  40. Palpable abdominal mass (45%) – classic presentation
  41. Weight loss
  42. Can elaborate a variety of hormones - “Paraneoplastic condition”
  43. Polycythemia (erythropoietin) – increased in RBC mass
  44. Hypercalcemia (PTH-like hormone): PTH = parathyroid hormone
  45. Hypertension (renin-like substance)
  46. Asymptomatic – detected by imaging
  1. Gross findings
  2. Characteristically a yellow-orange nodule (appears yellow due to fat)
  3. Highly vascular, cystic, and hemorrhagic
  4. Histology: Adenocarcinoma thought to arise from tubular epithelium; granular or clear cells commonly (clear due to fat)
  5. It can metastasize to lungs and bone, but almost any site/organ possible. Can enter renal vein and then proceed to right atrium. A doctor would have to put a patient on bypass to remove a tumor in the right atrium.
  6. Prognosis: Overall 5 year survival 70%
  7. Histology
  8. Adenocarcinoma arising from tubular epithelium
  9. Various cell types
  10. Clear cell (most common)
  11. Papillary
  12. Chromophobe
  13. Sarcomatoid
  14. Primary metastatic sites
  15. Lungs and bones
  16. Propensity to invade the renal vein and grow as a solid core
  17. Nephrectomy is the treatment of choice
  18. Five-year survival is ~45%
  1. Other Renal Neoplasms [S94]
  2. Benign epithelial neoplasms
  3. Papillary adenoma (≤ 0.5 cm)
  4. Oncocytoma
  5. Urothelial carcinoma
  6. Non-epithelial neoplasms

[End 44:05 min]