Pathology Flashcards
What are the 3 types of nephropathy in persons with hyperuricemic disorders?
- Acute uric acid nephropathy
- Chronic urate nephropathy (gouty nephropathy)
- Nephrolithiasis
What kind of crystal precipitate and where in acute uric acid nephropathy?
Uric acid crystals in renal tubules (collecting ducts)
*These can be seen on biopsy as bifiringent crystals that glow
WHat can the precipitation of uric acid crystals in acute uric acid nephropathy lead to?
Obstruction of nephrons and the development of acute renal failure
What patietns are more likely to get acute uric acid nephropathy?
People with leukemia or lymphoma undergoing chemo
-Chemo increases death of tumor cells and uric acid is produced as released nucleic acids are broken down
What kind of crystals are deposited in chronic urate nephropathy and where?
Monosodium urate crystals in distal tubules, collecting ducts and intersitium
What are chronic urate nephropathy crysals like?
They are variably birefringent (long and straight) needle-like crystals in the tubular lumens or interstitium (need to polarize them to see them)
What is a tophus and when do you see this?
- Foreign-body giant cells, other mononuclear cells and a fibrotic reaction (contain foreign elements to wall them off)
- Chronic urate nephropathy
What does tubular obstruction by urates cause?
Cortical atrophy and scarring
What % of individuals with gout have uric acid stones?
22%
What % of individuals with secondary hyperuricemia have uric acid stones?
42%
What disorders are associated with hypercalcemia?
- Hyperparathyroidism
- Multiple myeloma
- Vitamin D intoxication
- Metastatic cancer
- Excess calcium intake (milk-alkali syndrome) -Induce formation of calcium stones and deposition in the kidney
In hypercalcemia and nephrocalcinossi what is the earliest damage?
- Tubular epithelial cells: Mitochondrial distortion and other signs of cell injury (reverisible then irreversible)
- Calcium deposits: Mitochondria, cytoplasm, and basement membrane (purple, amorhpous)
- Calcified cellular debris: Obstruct tubular lumens (get actual stone formation), Obstructive atrophy of nephrons, secondary interstitial fibrosis, and inflammation (due to blockage)
What is the earliest functional defect in hypercalcemia and nephrocalcinosis?
Inability to concentrate the urine (this can be seen with many things though)
What are other tubular defects seen in hypercalcemia and nephrocalcinosis?
Tubular acidosis and salt-losing nephritis
What can further damage lead to in hypercalcemia and nephrocalcinosis?
Slowly progressive renal insufficiency (secondary to neprocalcinosis) if not taken care of
What do you see in acute phoshpate nephropathy?
Extensive accumulations of calcium phosphate crystals in tubules
What can cause acute phosphate nephropathy?
High doses of oral phosphate solutions in preparation for colonoscopy…patients aren’t hypercalcemic!!!
-This can crystalize without increase Ca levels, especially if there is poor renal function
What does acute phosphate nephropathy do?
Presents as renal insufficiency several weeks after exposure (renal function only partially recovers)
What is another name for light chain cast nephropathy?
Myeloma kidney
What is seen in light chain cast nephropathy?
Overt renal insufficiency
Who do you see light chain cast nephropathy in?
Half of those with multiple myeloma and related lymphoplasmacytic disorders
What are 4 contributing factors to renal damage in light- chain nepropathy?
- Bence Jones (light-chain) proteinuria and cast nephropathy
- Amyloidosis, of AL type formed from free light chains
- Light-chain deposition disease
- Hypercalcemia and hyperuricenia
Why do Bence Jones (light-chain) proteins contribute to renal damage in light chain nepropathy?
They are directly toxic to epithelial cells and combine with the urinary glycoprotein (Tamm-Horsfall protein) under acidic conditions forming large, histologically distinct tubular casts that obstruct the tubular lumens and induce a characteristic imflammatory reaction around the casts –> Light-chain cast nephropathy
What can be done to see Bence Jones (light-chain) proteinuria and cast nephropathy?
Serum or urine** electrophoresis
What is light-chain deposition disease
- Deposition of light chains (usually kappa) in GBMs and mesangium (glomerupathy)
- Tubular BM (tubulointerstitial nephritis)
Describe Bence-Jones Tubular Casts
- Pink to blue amorphous masses: Concentrically laminated, Fill and distend the tubular lumens
- No nuclei
- Surrounded by multinucleate giant cells
- Nonspecific inflammatory response and fibrosis: Adjacent interstitial tissue
What does obstruction increase the susceptibility to?
Infection and stone formation
What can unrelieved obstruction lead to?
Permanent renal atrophy… hydronephrosis (kidney swells) or obstructive uropathy (NEED TO DEAL WITH THIS)
How can unrelieved obstructions be death with?
Surgery (stents, lithotripsy, antibiotics) or medically treatable
What is hydronephrosis?
Dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine
In complete obstruction does glomerular filtration continue?
Yes, filtrate subsequently diffuses back into the renal interstitium and perirenal spaces ultimately returning to the lympthatic and venous systems… the affected calyces and pelvis become dilated
What are the initial functional alterations in the tubule in hydronephrosis?
Impaired concentrating ability (GFR falls later)
What 3 things are seen with sudden and complete obstruction?
- Glomerular filtration is reduced
- Mild dilation of the pelvis and calyces
- Atrophy of the renal parenchyma (not frequent–> tissue will still function…it won’t die off)
What 2 things are seen with subtotal or intermittent obstruction?
- Glomerular filtration is not suppressed (no total blockage…stuff is still getting out)
- Progressive dilation ensues
What is the morphology of the kidneys in hydronephrosis?
They are slightly to massively enlarged (dilated) and this depends on the degree and duration of the obstruction (how long and where it is)
What are early features seen in the kidney during hydronephrosis?
- Simple dilation of the pelvis and calyces
- Significant intersitial inflammation
What is seen in chronic cases of hydronephrosis?
- Cortical tubular atrophy
- Marked diffuse interstitial fibrosis (due to irritation and inflammation)
- Progressive blunting of the apices of the pyramids
What happens to the kidneys in advanced cases of hydronephrosis?
- The kidney becomes a thin-walled cystic structure with a diameter of up to 15-20cm
- There is parenchymal atrophy, total obliteration of the pyramids, and thinning of the cortex (it reduces to nothing)
Are men or women more commonly affected by urolithiasis?
Men
What is he peak age of onset for urolithiasis?
20-30 years
Is there a familial and hereditary predisposition to stone formation?
Yes
What are examples of hereditary disease that can lead to excessive production and excretion of stone-forming substances?
Inborn errors of metabolism: Gout, cystinuria, and primary hyperoxaluria
What is primary hyperoxaluria?
The liver makes calcium oxalate so there is lots of stone production (this requires a liver and kidney transplant
What are the 4 main types of calculi?
- Calcium stones (70%)
- Triple stones or struvite stones (15%)
- Uric acid stones (5%-10%)
- Cystine stones (1%-2%)
What is the most important determinant of stone formation?
Increased urinary concentration of the stones’ constituents…this exceeds their solubility (supersaturation)
What else can favor supersaturation in some metabolically normal patients?
Low urine volume
What are calcium stones make of?
Calcium oxalate or calcium oxalate mixed with calcium phosphate
Are calcium stones radiopaque?
Yes
What % of patients with calcium stones have hypercalcemia and hypercalciuria?
5%
What conditions are associated with hypercalcemia and hypercalciuria?
- Hyperparathyroidism
- Diffuse bone disease
- Sarcoidosis
What % of patients with calcium stones have hypercalciuria without hypercalcemia?
55%
WHat things can cause hypercalciuria without hypercalcemia?
- Hyperabsorption of calcium from intestine (absorptive hypercalciuria)
- Intrinsic impairment in renal tubular reabsorption of calcium (renal hypercalciuria)
- Idiopathic fasting hypercalciuria with normal parathyroid function
What are triple stones also called?
Struvite stones
What are triple stones made of?
Magnesium ammonium phosphate
What are the largest triple stones called and where are they found?
Staghorn calculi and they occupy the large portions of the renal pelvis
What are triple stones caused by?
Bacteria: Proteus and some staphlyococci
-They convert urea to ammonia and the resultant alkaline urine causes the precipitation
What 2 conditions are uric acid stones common in?
Hyperuricemia (gout) and diseases with rapid cell turnover (leukemias)
What will more than 50% of patients with uric acid stones have?
Neither hyperuricemia nor increased urinary excretion of uric acid
Are uric acid stones radiopaque?
No, they are radiolucent
What are cystine stones from?
Cystinuria:
- Inherited genetic disorder of the transport of an AA
- Excess cystine in the urine (cystinuria) and the formation of cystine stones
Where are casts found?
In the urinary sediment (need to look at them under a microscope)
What can casts do?
Localize disease to a specific location in the GU tract (the can’t diagnose anything themselves, but can be combined with other clinical clues for diagnosis)
What are casts?
Coagulum of Tamm-Horsfall mucoprotein and the trapped contents with the tubular lumen
Where do casts originate from?
The DCT or collecting ducts
When do casts form?
In periods of urinary concentration or stasis or when the urine pH is very low
What does the cylindrical shape of the cast reflect?
The tubule in which they were formed
What are some prominent cellular elements that determine the type of cast?
Hyaline, erythrocyte, leukocyte, epithelial, granular, waxy, fatty, broad
What are hyaline casts made of?
Mucoprotein (Tamm-Horsfall protein) secreted by tubule cells
Where are hyaline casts formed?
The collecting duct
What produces a RBC cast?
Glomerular inflammation with leakage of RBCs (usually extravasation of RBC in glomerular area)
*RBC casts are formed in the distal convoluted tubule
What are WBC casts most typical for?
Acute pyelonephritis*
-Can also be seen in glomerulonephritis or with inflammation of the kidney
Where are cellular casts from?
Within the nepron
How might a waxy cast be ultimately formed?
Before being flushed into the bladder urine, cells may degenerate to become a coarsely granular cast, later a finely granular cast, and ultimately, a waxy cast
Where do granular and waxy casts arise from?
Renal tubular cell casts
What lines the renal pelvis, ureters, bladder, and urethra?
A special form of transitional epithelium (urothelium)
Describe the surface layer of the renal pelvis, ureters, bladder, and urethra?
Large, flattened “umbrella cells” with abundant cytoplasm that horizontally covers several underlying cells
Do the renal pelvis, ureters, bladder, and urethra have a well developed BM?
Yes
What is a feature of the lamina propria in the renal pelvis, ureters, bladder, and urethra?
Wisps of smooth muscle that form a discontinuous muscularis mucosae
Why is it important to differentiate muscularis mucosae from deeper muscle bundles of the detrusor muscle (muscularis propria)?
Bladder cancers are staged on the basis of invasion of the muscularis propria (need to know the invasion of tumors)
What % of autopsies contain congential anomalies in the ureters?
2%-3%
What does ureteropelvic junction (UPJ) obstruction result in?
Hydroneprosis
Who does UPJ obstruction present in?
Infants or children, more common in boys
What % of cases is UPJ obstruction bilateral?
20%
What is commonly seen in UPJ obstruction?
Other congential anomalies
What is the most common cause of hydronephrosis in infants and children?
UPJ obstruction
What 2 congential anomalies can lead to infection, chronic infection, fibrosis, and other problems?
UPJ obstruction or vesicouretral reflux
In adults, who is UPJ obstruction more common in?
Women and unilateral
What is inflammation of the ureters?
Ureteritis
If ureteritis associated with infection?
No
Does ureteritis have significant clinical consequence?
No
What is the morphology of ureteritis?
Accumulation or aggregation of lymphocytes (because no infection) that form germinal centers in the subepithelial region (little bumps that can be cyst-like), causing slight elevations of the mucosa and producing a fine granular mucosal surface (ureteritis folicularis)
In ureterits, what might the mucosa contain?
Scattered fine cysts (1-5mm) what are lined by flattened urothelium (ureteritis cystica)
Are primary tumors of the ureter common?
No, they are rare
Where do small benign tumors of the ureter originate?
Mesenchyme
What are fibroepithelial polyps?
- Like a skin-tag in the lumen of the ureter
- Tumor-like lesion
- Grossly presents as small mass projecting into the lumen
- Often in children
- Loose, vascularized connective tissue mass lying beneath the mucosa
What do primary malignant tumors of the ureter resemble?
Those arising the the renal pelvic, calyces, and bladder
What are the majority of primary malignant tumors of the ureter?
Urothelial carcinomas
When are primary malignant tumors of the ureter found most frequently?
During the 6th and 7th decades of life
What can primary malignant tumors of the ureter cause?
Obstruction of the ureteral lumen
Can tehre be multipl primary malignant tumors of the ureter?
Yes
What is a diverticula?
A pouchlike-evagination of the bladder wall
What are the 2 ways diverticula of the bladder arise?
- As congential defects
2. As acquired lesions
What causes congenital bladder diverticula?
- Focal failure of development of the normal musculature
- Urinary tract obstruction during fetal development
Are most diverticula of the bladder acquired or congenital?
Most are acquired
What causes acquired bladder diverticula?
Persistent urethral obstruction
- Prostatic enlargement: Hyperplasia or neoplasia
- Holding bladder to long, too often
What is the morphology of bladder diverticula?
- Multiple
- Round to ovoid, saclike pouch
- Varies from less than 1cm to 5-10cm in diameter
Why are bladder diverticula clinically significant?
- They constitute sites of urinary stasis
2. They predispose to infection and the formation of bladder calculi
What causes bladder extrophy?
Developmental failure in the anterior wall of the abdomen and bladder
What happens in bladder extrophy?
They bladder either communicates directly through a large defect with the surface of the body or it lies as an opened sac
What can happen to the exposed bladder mucosa in bladder extrophy?
- It might undergo colonic glandular metaplasia
2. It is subject to infections that often spread to upper levels of the urinary system
What else is the patient at risk for with bladder extrophy?
Increased risk of adenocarcinoma arising in the bladder remnant (Not the bladder itself)
-Because the mucosa is exposed, it can undergo metaplasia
What coliforms are common etiologic agents of cystitis?
- E. Coli
- Proteus
- Klebsiella
- Enterobacter
Who is more likely to develop cystitis?
Women (again, they have shorter urethras)
What is tuberculous cystitis?
The sequelae to renal tuberculosis
In patients who are immunosuppressed or those receiving long-term antibiotics, what types of this cause cystitis?
- Candida albicans
2. Cryptococcal agents
What can cause cystitis if you have been traveling?
Schistosomiasis (Schistosoma haematobium)
What are predisposing factors to cystitis?
- Bladder calculi
- Urinary obstruction
- DM
- Intrumentation: Procedures can cause inflammation and irritation
- Immune deficiency
What is a treatment that can cause cystitis?
Radiation: Can cause inflammation and fibrosis if you get irradiation of the bladder region
What is the gross appearance in nonspecific acute or chronic inflammation of the bladder?
Hyperemia of the mucosa with possible exudate
What kind of infilatrate is seen in acute cystitis?
Acute inflammatory infiltrate with neutrophils
-This will be boggy, edematous, red, hot/bothered, maybe even exudate
What kind of infilatrate is seen in chronic cystitis?
Chronic inflammatory infiltrate with leukocytes/lymphocytes
What happens in follicular cystitis?
Aggregation of lymphocytes into lymphoid follicles in the bladder mucosa and underlying wall
-Looks like lymphoid tissue with collections of ink dots everywehere
What is eosinophilic cystitis caused by and manifested by?
It is caused by parasites (maybe schistosomiasis) and is manifested by infiltration with submucosal eosinophils
What is interstitial cystitis (chronic pelvic pain syndrome)
Persistent, painful form of chronic cystitis (lymphocyte infiltration)
Who do you see interstitial cystitis more commonly in?
Women
What are symptoms of interstisial cystitis?
Intermittent, severe suprapubic pain, urinary frequency, urgency, hematuria, dysuria…. feels like a UTI but no infection (pain, urinary issues, pelvic dysfunction)
Is there evidence of bacterial infection in interstitial cystitis?
No
What are some cystoscopic findings in intersitial cystitis?
- Fissures (breaks in the mucosa)
- Punctate hemorrhages (glomerulations)
What can be seen in the late phase of interstitial cystitis?
Chronic mucosal ulcers (Hunner ulcers) which are seen in the late (classic, ulcerative) phase of cystitis
What is malacoplakia?
- Peculiar pattern of vesical inflammatory reaction
- Soft, yellow, slightly raised mucosal plaques, 3-4cm in diameter
- Infiltration with large, foamy macrophages, mixed with occasional multinucleated giant cells and interspersed lymphocytes (like ink dots)
What are Michaelis-Gutmann bodies?
Laminated mineralized concentrations within macrophages seen in Malacoplakia (they are random dark dots that are too big to be a lymphocyte)
What is malacoplakia related to?
Chronic bacterial infection:
- E. COLI***
- Proteus (occassionally)
- Increased frequency in immunosuppressed transplant recipients
What is associated with malacoplakia in terms of macrophages?
Defects in phagocytic or degradative function of macrophages… the phagosomes become overloaded with undigested bacterial products
-These patients might always be sick since their macrophages are dysfunctional
What is polypoid cystitis?
An inflammatory condition/irritation to the bladder mucosa
What is the most common culprit of polypoid cystitis?
Indwelling catheters are the most common culprits (ICU, nursing home), but any injurious agent may give rise to this lesion
What is seen in the urothelium of polypoid cystitis?
Broad bulbous polypoid projections secondary to submucosal edema (due to the edema/inflammation)
What can polypoid cysitis be confused with?
Papillary urothelial carinoma (clinically and histologically)
What is cystitis cystica and cystitis glandularis?
Common lesions of the urinary bladder that are nests of urothelium (Brunn nests) that grow downward into the lamina propria (these can also be confused with urothelial CA)
What do central epithelial cells transform into in cystitis glandularis?
Cuboidal or columnar epithelium lining
GLANDS ..it can become more glandular like goblet cells)
What do central epithelial cells transform into in cystitis cystica?
Cystic spaces filled with clear fluid lined by flatten urothelium (Dilations
Do cystitis cystica and cystitis glandularis often coexist?
Yes… this is reffered to as cystitis et glandularis
Is cystitis et glandularis and incidental finding in normal bladders?
Yes, there’s nothing to do about it
If you see cystic spaces in the bladder do you instantly think cancer?
NOPE… could be cystitic cystica or other things
What does nephrogenic ademona result from?
Shed renal tubular cells that implant in sites of injured urothelium
What does neprogenic ademona resemble histologicall?
Renal tubules
What can happen to the overlying urothelium in nephrogenic adenoma?
It might be focally replaced by cuboidal epithelium and assume a papillary growth pattern
How big are nephrogenic adenomas?
Typically less than a cm, but lesions may be sizeable and may resemble cancewr clinically
(You have to biopsy it because is may be small and can look like CA)
What % of cancers are bladder cancer?
7%
What % of cancer mortality in the US is due to bladder cancer?
3%
What % of bladder tumors are of epithelial origin?
95%
Bladder tumors of epithelial origin are composed of what and also called what?
- Composed of urothelial (transitional cell) type
- Interchangeable called urothelial or transitional tumors
What other types of tumors may occur?
Squamous and glandular carcinomas as well as mesenchymal
What % of bladder tumors are urothelial tumors?
90%
What are 2 distinct precursor lesions to invasive urothelial carincoma?
- Non-invasive papillary tumors
2. Flat non-invasive urothelial carcinoma
What is the most common precursor lesion?
Non-invasive papillary tumors
Where do non-invasive papillary tumors originate from
Papillary urothelial hyperplasia (these are graded on biological behavior
What is another name for flat non-invasive urothelial carcinoma?
Carcinoma in situ (CIS)
Describe carcinoma in situ
- Epithelial lesions for cytologic changes of malignancy
- Confined to the epithelium, without BM invasion
- High grade
What are 3 features seen in patient with invasive bladder cancer?
- The tumor has already invaded the bladder wall
- No precursor lesions may be detected (the precursor lesion has been destroyed by the high-grade invasive component…large, ulcerated mass)
- Invasion into the lamina propria worsens the prognosis: Major decrease in survival is associated with invasion of the muscularis propria (detrusor muscle)
WHat is the mortality rate with invasion of the muscularis propria?
30% 5 year mortality rate
What are gross patterns of urothelial tumors?
Purepapillary to nodular or flat
Describe papillary lesions
Red, elevated excrescences, exophytic papillomas, true papillary structure has a fibrovascular core
Are the majority of papillary tumors low grade?
YES
Where do most papillary tumors arise from?
Lateral or posterior walls at bladder base
What patients get papillar lesions?
Younger patients
What are papillary urothelial neoplasma of low malignant potential (PUNLMPs)?
They are similar to papilloma, but have thicker urothelium and diffuse nuclear enlargement
Are PUNMLPs associated with invasion?
No
Do PUNLMPs recur as higer grade tumors associated with invasion and progression?
No, this rarely happens
What do low-grade papillary urothelial carcinomas look like?
- Orderly appearance: Architecturally and cytologically
- Cells are evenly spaced and cohesive
- Few atypical nuclei
- Infrequent mitotic figures
- Mild variation in nuclear size and shape
Can low-grade papillary urothelial carcinomas recur and invade?
YES…although this is rare
What to high-grade papillary urothelial cancers look like?
- Contain discohesive cells
- Large hyperchromatic nuclei
- Frank anaplasia
- Frequent mitotic figures
- Disarray and loss of polarity
Do high-grade papillary urothelial cancers have a higher incidence of invasion into the muscular layer?
Yes…they have a higher risk of progression than low-grade lesions
When invasion is present in high-grade papillary urothelial cancers, is there a significant metastatic potential?
Yes
What % of bladder cancers in the US are caused by squamous cell carcinoma?
3-7%
What are squamous cell carcinomas caused by?
Chronic bladder irritation and infection
What are the tumors like in squamous cell carcinomas?
Invasive, fungating, infiltrative, ulcerative
What are adenocarcinomas of the bladder like?
Histologically identical to those seen in the GI tract (these are rare though)
What are small-cell carcinomas that arise in the bladder associated with?
Urothelial, squamous, or adenocarcinoma
What are clinical features of urothelial CA?
- Classically produce a painless hematuria: Dominant and sometimes only clinical manifestation
- Frequency, urgency, and dysuria occasionally accompany the hematuria (but the 1st 3 can be due to other things)
If you have hmeaturia, what should you do?
Get worried and do a cystoscopy…when you see the lesion go from there
What does progsosis of urothelial CA depend on?
- Histological grade of the papillary tumor
- Stage at diagnosis
What are some causes of urothelial carcinoma?
- Cigarette smoking*: Most important influence and Increases risk threefold to sevenfold
- Cigars, pipes, and smokeless tobacco are associated with a smaller risk
- Industrial exposure to arylamines—particularly 2-naphthylamine: Cancers appear 15 to 40 years after* the first exposure
- Schistosoma haematobium infections in endemic areas (Egypt, Sudan)
- Long-term use of analgesics is implicated, as it is in analgesic nephropathy (chronic pain patient)
- Heavy long-term exposure to cyclophosphamide-I
- Prior exposure of the bladder to irradiation
What do schistosoma haematobium infections do in the bladder?
- Ova are deposited in the bladder wall and incite a brisk chronic inflammatory response
- This induces progressive mucosal squamous metaplasia and dysplasia
What is cyclophosphamide?
An immunosuppressive agent that causes hemorrhagic cystitis
What are the 3 genetic alterations seen in urothelial CA?
- Chromosome 9 monosomy
- Deletions of 9p and 9q
- Deletions of 17p, 13q, 11p, and 14q
What can cause obstruction in the renal pelvis?
Calculi, tumors, uteropelvic stricture (fibrosis/inflammation)
What can cause intrinsic obstruction in the ureter?
Calculi, tumors, clots, sloughed papillae inflammation (Necrotic: Analgesic nephropathy)
What can cause extrinsic obstruction in the ureter?
Pregnancy, tumors (cervic or ovarian), retroperitoneal fibrosis…infection surgery, ect.
What can cause obstruction in the bladder?
Calculi, tumors, functional (neurogenic)
What can cause obstruction in the prostate?
Hyperplasia, carcinoma, prostatitis
What can cause obstrction in the urethra?
Posterior valve stricture, tumors
