Pathology Principles

Question 1

What poison can lead to acute tubular necrosis?

Answer 1

Ethylene glycol - has distinct characteristic of vacuolization and dilation

Question 2

What is a severe but uncommon complication of acute pyelonephritis which is more likely to occur in diabetics?

Answer 2

Papillary necrosis

Question 3

What are the morphologic hallmarks of chronic pyelonephritis?

Answer 3

Coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces and flattening of the papillae

Question 4

What is polyomavirus nephropathy?

Answer 4

Emerging viral pathogen that can cause pyelonpehritis is polyomavirus, specifically the BK virus. Significant in kidney transplant patients because can have reactivation of this infection due to immunosuppression. This can lead to allograft failure in 1-5% of kidney transplant recipients.

Question 5

What is the most common causative agent of acute drug-induced interstitial nephritis?

Answer 5

Methicillin. It commonly occurs with synthetic penicillins such as this. Will see symptoms of fever, eosinophilia, rash, and renal abnormalities (hematuria, proteinuria, and leukocyturia). Morphologically, see edema and infiltration of mononuclear cells (especially lymphocytes and macrophages)

Question 6

What is analgesic nephropathy?

Answer 6

Renal disease caused by excessive intake of analgesic mixture of medications with characteristics of tubulointerstitial nephritis and renal papillary necrosis. With drug withdrawal, renal function may stabilize or improve. More common in women.

Question 7

What is acute uric acid nephropathy?

Answer 7

Seen in patients with massive cell lysis aka cancer patients who are on chemotherapy - these patients have precipitation of uric acid crystals in renal tubules leading to obstruction and acute renal failure.

Question 8

What is chronic irate nephropathy?

Answer 8

Seen in gout patients due to deposition of monosodium urate crystals. These deposits form tophi on which infection can occur

Question 9

What is myeloma kidney?

Answer 9

In multiple myeloma, have an excessive amount of light chains which can lead to formation of amyloid which can deposit in kidneys. See Bence Jones proteinuria (occurs in 70% of multiple myeloma patients) as well as cast nephropathy. Light-chain cast nephropathy specifically refers to when Bence Jones proteins combine with the urinary glycoprotein (Tamm-Horsfall) to cause large tubular casts that can obstruct tubular lumen

Question 10

What’s the difference between papillary necrosis in pyelonephritis vs. analgesic nephropathy?

Answer 10

In pyelonephritis, papillary necrosis is a rare complication of disease and is usually in diabetics. In contrast, analgesic nephropathy usually has it occurring first with cortical tubulointerstitial nephritis following it. The necrosis seems to be due to a combo of toxic effects and ischemic injury.

Question 11

What is benign nephrosclerosis?

Answer 11

Can be seen in the absence of hypertension and usually morphologically see medial hypertrophy, reduplication of the elastic lamina, and increased myofibroblastic tissue in the intima. More commonly seen in blacks and characterized by hyaline deposition. Usually GFR is normal.

Question 12

What is malignant nephrosclerosis?

Answer 12

Frequently due to a malignant/accelerated phase of hypertension, it is more common in men and blacks. Kidneys have a “flea-bitten” appearance and you see fibrinoid necorsis of arterioles and intimal thickening (onion-skin). Symptoms include papilledema, retinal hemorrhages, encephalopathy, etc.

Question 13

What is unilateral renal artery stenosis?

Answer 13

Unilateral stenosis is an uncommon cause of hypertension, but when it occurs it is either due to an atheromatous plaque (more common in men and 70% of time) or fibromuscular dysplasia (more common in women). Overall, the thinning of the arteriolar lumen leads to increased renin release

Question 14

How are typical and atypical hemolytic uremic syndrome different?

Answer 14

Typical HUS is due to infection from E. coli and usually presents with sudden onset of bleeding. Renal failure is managed by dialysis and most patients recover. Trigger is Shiga toxin in E. coli.
Atypical HUS is due to an inherited deficiency in complement (most commonly factor H) and is characterized by multiple relapses and progression to ESRD. Patients do not fare as well as those with typical HUS.

Question 15

How does TTP affect the kidney?

Answer 15

TTP is due to deficient ADAMTS-13 metalloproteinase activity and is commonly caused by inhibitory autoantibodies to this disorder (most often in women). Classic symptoms are fever, acute renal failure, neurologic changes, thrombocytopenia, and microangiopathic hemolytic anemia. Renal involvement is seen in only 50% of the cases.

Question 16

Why are infarcts common in the kidneys?

Answer 16

The kidneys do not have a lot of collateral circulation present. When infarcts do occur, there is a wedge-shaped zone of coagulative necrosis due to loss of blood supply as well as resultant tissue ischemia. Can be the result of embolization of cardiac valvular vegetations or a cardiac mural thrombus.

Question 17

How does multi cystic kidney disease differ from ARPKD?

Answer 17

First, the outside of the kidneys will look more abnormal with cysts replacing the renal parenchyma. Involvement is often often unilateral (ARPKD is bilateral), but when it is bilateral, it is usually asymmetric.

Question 18

How does presentation of autosomal dominant PKD differ due to mutations in PKD-1 vs. PKD-2?

Answer 18

PKD-1 mutations usually involve and are localized to tubular epithelial cells while PKD2 disease is throughout the entire nephron/tubule.

Question 19

What is the most common mutation in autosomal recessive PKD?

Answer 19

PKHD1 gene mutation from chromosomal region 6p21-23. This encodes an abnormal fibrocystin protein - fibrocystin is normally found on renal tubular and bile duct epithelial cells and thus this is why you see renal cysts and congenital hepatic fibrosis in these patients.

Question 20

How can you tell where the point of obstruction originates in hydronephrosis?

Answer 20

If unilateral, process originates from the ureteral orifice to that of the pelvis. If bilateral, then the problem would originate in the bladder trigone or urethra

Question 21

What kind of renal stones are commonly formed after infection?

Answer 21

Magnesium ammonium phosphate stone

Question 22

What is the most significant risk factor for renal cell carcinoma?

Answer 22

Smoking

Question 23

What is the most common type of renal cell carcinoma?

Answer 23

Clear-cell carcinoma makes up 70-80% of the renal cell cases. 98% of these tumors have VHL gene mutation. Most likely from proximal tubule epithelium
Have a tendency to invade the renal vein and can even grow up the IVC into the heart.
Classic histologic appearance of neoplastic cells with clear cytoplasm arranged in nests with intervening blood vessels

Question 24

What is a Wilm’s tumor?

Answer 24

Childhood kidney tumor due to mutation in WT-1 gene. Commonly presents before the age of 10 years old. Histologically, see nests and sheets of dark blue cells which can compress normal renal parenchyma.

Question 25

What are syndromes associated with Wilm’s Tumor?

Answer 25

Denys-Drash: a syndrome in which you have gonadal dysgenesis, early-onset nephropathy, and 90% chance of Wilm’s
Beckwith-Wiedemann: see enlargement of body organs, macroglossia, hemihypertrophy, omphalocele, and abnormal adrenal cortex
WAGR: See aniridia, genetic anomalies, mental retardation and a 33% chance of developing Wilm’s

Question 26

What is the direct pathway for graft rejection?

Answer 26

When the T cells of a transplant recipient recognize donor MHC molecules on the surface of APC’s in the graft with the dendritic cells from donor organ most important for initiation response.
CD8 cells are transformed into CTL’s which attack the graft cells.

Question 27

What is the indirect pathway for graft rejection?

Answer 27

Involves T lymphocytes recognizing MHC antigens of the graft donor after they are presented by the recipient’s own APC’s - have uptake and processing of the host APC which leads to generation of CD4+ cells that enter graft and lead to delayed hypersensitivity type of reaction.

Question 28

What is the more common form of diverticula?

Answer 28

Acquired diverticular due to persistent urethral obstruction
In men, this is commonly because of prostatic enlargement which obstructs the urine flow and induces thickening of the bladder wall.
Diverticula represent potential sites of infection as well as potential metaplasia sites (i.e. carcinoma)

Question 29

What is extrosphy?

Answer 29

When there’s a developmental failure of the anterior abdominal wall and the bladder communicates directly through a large defect
May undergo colonic glandular metaplasia leading to adenocarcinoma

Question 30

What type of cystitis is commonly seen in immunocompromised patients?

Answer 30

Cystitis caused by Candida

Question 31

What is interstitial/Hunner cystitis?

Answer 31

Painful form of chronic cystitis that occurs more frequently in women and has symptoms of severe suprapubic pain with urinary frequency, urgency, hematuria, and dysuria without evidence of bacterial infection. May see features of chronic mucosal ulcers called Hunner ulcers as well as transmural fibrosis

Question 32

What is malakoplakia?

Answer 32

A form of vesical inflammatory reaction characterized by soft, yellow, and slightly raised mucosal plaques as well as large foamy macrophages with occasional multinucleate giant cells. May see concretions called Michaelis-Gutmann bodies.
Related to chronic bacterial infection (i.e. E. coli or Proteus)

Question 33

What are characteristics of urothelial carcinoma?

Answer 33

Can occur anywhere you have urothelial epithelium but most commonly in the bladder. Often multifocal when found and have a tendency to recur; when they have been found, commonly have penetrated the bladder wall and thus cannot find a precursor lesion.
Risk factors include smoking, exposure to polycyclic aromatic hydrocarbons, and family history.

Question 34

What is squamous cell carcinoma of the bladder associated with?

Answer 34

Schistosoma infections - thus it is more common in regions in which this is endogenous.

Question 35

What is a urethral caruncle?

Answer 35

An inflammatory lesion that presents as a small, red, painful mass around the external urethral meatus and is usually in older females. May be covered by an intact mucosa but is extremely sensitive to trauma and thus can ulcerate and bleed

Question 36

What is a condyloma acinatum?

Answer 36

A benign lesion that is associated with infection from HPV type 6 and 11. It is sexually transmitted and occurs on external genitalia. Tends to recur but only rarely progresses to invasive cancers.

Question 37

What is squamous cell carcinoma of the penis?

Answer 37

Uncommon malignancy in the US since circumcision is common here (circumcision offers protection usually due to promotion of better genital health)
Risk factor includes infection with HPV type 16 and smoking.

Question 38

What is bowenoid papulosis?

Answer 38

Tumor that occurs in sexually active adults with a younger age of onset. Associated with HPV 16

Question 39

What is bowen disease?

Answer 39

It can occur in the genital region of both mean and women and is usually seen over the age of 35. It appears as a solitary, thickened, gray-white opaque plaque. Essentially it is carcinoma in situ of the penis.

Question 40

What is the most common cause of prostatitis seen today?

Answer 40

Chronic abacterial prostatitis

Question 41

What can prostatic hyperplasia lead to overtime due to complications from urethral obstruction?

Answer 41

Can cause bilateral hydronephrosis, renal cortical atrophy, and eventual renal failure

Question 42

Why do you not see WBC casts in acute cystitis?

Answer 42

Because the infection involves just the bladder - it would only lead to cast formation if the infection progressed up further and involved the renal tubules.

Question 43

What will you commonly find in the urine of patients with drug-induced interstitial nephritis?

Answer 43

Eosinophils. This is essentially an allergic reaction

Question 44

What is a paraneoplastic syndrome associated with renal cell carcinomas?

Answer 44

Hypercalcemia. This is most likely due to elaboration of parathormone-related peptide by the neoplasm.

Question 45

What are signs/symptoms of a nephrotic syndrome?

Answer 45

Heavy proteinuria as well as hypoalbuminemia (albumin lost beyond the liver’s capacity to synthesize), hypogammaglobulinemia (increased risk of infection), hyper coagulable state (due to anticoagulant), hyperlipidemia and hypercholesterolemia, severe edema (especially in periorbital regions), and sodium/water retention
Urine is usually foamy due to increased proteinuria

Question 46

What are signs/symptoms of a nephritic syndrome?

Answer 46

Usually caused by disorders from glomerular inflammation and bleeding and present with limited proteinuria, oliguria, azotemia, salt retention with periorbital edema, and grossly visible hematuria (RBC casts and dysmorphic RBC’s seen)
Presentation can be acute proliferative glomerulonephritis or rapidly progressive

Question 47

What is the hallmark of acute renal failure?

Answer 47

Azotemia (increased BUN and creatinine) along with oliguria (low urine output) or anuria (no urine flow)

Question 48

What is pre renal azotemia?

Answer 48

Due to decreased blood flow to kidneys and is a common cause of acute renal failure
Decreased blood flow results in decreased GFR, azotemia, and oliguria/hypouresis
There is reabsorption of BUN out of proportion to creatinine so that the BUN:creatinine ratio is significantly elevated (greater than 20:1)

Question 49

What is post renal azotemia?

Answer 49

Caused by obstruction of urinary tract downstream from the kidney leading to decreased GFR, azotemia, and oliguria
In early stages of obstruction, have increased tubular pressure essentially “forcing” BUN into the bloodbath tubular function remaining intact, but overtime there’s decreased reabsorption of BUN and sodium

Question 50

What is acute tubular necrosis?

Answer 50

Injury and necrosis of tubular epithelial cells and is the most common cause of acute renal failure (with intrarenal azotemia)
Necrotic cells plug up tubules and obstruction causes a decreased GFR
There’s decreased reabsorption of BUN so that the BUN:creatinine ratio remains WNL; there’s also decreased reabsorption of sodium and inability to concentrate urine
Can be use to ischemic or nephrotoxic damage

Question 51

What is the most common cause of nephrotoxic acute tubular necrosis?

Answer 51

Aminoglycosides

Question 52

What is uremia?

Answer 52

INcreased amount of nitrogenous waste products in the blood that can result in nausea, anorexia, pericarditis, pneumonitis, platelet dysfunction, encephalopathy and deposition of urea crystals in the skin

Question 53

What are clinical features of chronic renal failure?

Answer 53

Uremia, salt and water retention with resultant hypertension, hyperkalemia with metabolic acidosis, anemia, hypocalcemia, and renal osteodystrophy due to secondary hyperparathyroidism
Most patients are hypertensive with dominant symptoms that are cerebral and cardiac