Cystitis, Pyelonephritis and Interstitial Nephritis Flashcards
(57 cards)
1
Q
Cystitis
A
- Inflammation of urinary bladder, most often due to bacterial infection. The upper urinary tract is usually not involved.
- Especially important as antecedent to pyelonephritis
2
Q
Pyelonephritis
A
- Inflammation of upper urinary tract: renal pelvis, tubules, and interstitium, most frequently due to bacterial infection.
- Glomeruli are usually not involved.
3
Q
Bacteriuria
A
- Bacteria in the urine.
- May be associated with clinical urinary tract Infection (UTI) or may be asymptomatic.
4
Q
Interstitial Nephritis
A
•Inflammation of renal interstitium, and to a lesser degree the tubules, with no or minimal involvement of glomeruli.
5
Q
Vesicouretral Reflex (VUR)
A
•Retrograde urine flow from bladder into uterus + kidney
6
Q
Reflux Nephropathy
A
•Functional and pathologic changes in kidney resulting from VUR.
7
Q
Cystitis - Symptoms
A
• Triad of symptoms:
– Frequency of urination
– Lower abdominal pain
– Dysuria
• Usually does not give rise to constitutional symptoms
– Occasionally: Fever, chills, malaise
8
Q
Cystitis - Organisms
A
Causative organisms:
• Most common:
-E. coli >> Proteus, Klebsiella, Enterobacter
• Rare:
– M. tuberculosis
– Candida
– Viruses
– Chlamydia
– Schistosoma - parasite
*Important as a risk factor for squamous cell carcinoma
*Highest incidence in Africa, South America, Middle East, Egyp
9
Q
Cystitis - Predisposing Factors
A
- Bladder calculi
- Urinary obstruction
- Diabetes mellitus
- Instrumentation
- Immune deficiency
- Cytotoxic drugs (cyclophosphamide)
– Hemorrhagic cystitis
• Radiation
10
Q
Acute Cystitis - Pathological Findings (Gross)
A
• Gross
– Hyperemia (reddening) of mucosa
– Exudate
– If large amounts of hemorrhage = Hemorrhagic cystitis
– If large areas of ulceration = Ulcerative cystitis
11
Q
Acute Cystitis - Pathological Findings (Microscopic)
A
• Microscopic
– Neutrophilic infiltrate, hemorrhage, ulceration of mucosa
12
Q
A
Hemorrhagic Cystitis
13
Q
Chronic Cystitis
A
• Persistence of infection
– Longer duration
• Pathologic findings:
– Chronic infiltrate, mostly lymphocytes, plasma cells
– Heaped up and reactive urothelium
– Fibrous thickening of muscularis propria
• Leads to decreased contractility
14
Q
Chronic Cystitis - Special Histologic Forms
A
- Follicular cystitis
- Eosinophilic cystitis
- Interstitial cystitis
- Malacoplakia
- Polypoid cystitis
- Emphysematous cystitis
- Cystitis cystica
15
Q
A
- Chronic Follicular Cystitis
- Aggregation of lymphocytes with lymphoid follicles
16
Q
A
- Eosinophilic Cystitis
- Submucosal eosinophils, fibrosis and occasional giant cells
- Rarely part of a systemic allergic disorder
17
Q
Interstitial Cystitis
A
- Most frequent in women
- Inflammation and fibrosis in all layers of the bladder wall, often with ulceration
– Can mimic gross appearance of carcinoma in situ (CIS)
- Highly incapacitating and difficult to treat
- Symptoms:
- Intermittent and severe suprapubic pain
- frequency
- urgency
- hematuria
- dysuria
18
Q
A
- Malakoplakia - cystitis
- Unique form of chronic cystitis; caused by chronic E. coli infection
- Immunosuppressed patients (esp. transplant recipients)
- Similar inflammatory process can occur in kidney, colon, lungs, and prostate
- Pathologic features:
– Gross: Multiple yellowish plaques in mucosa and submucosa
19
Q
A
- Malakoplakia - cystitis
- Microscopic Pathologic features:
- Large foamy macrophages, multinucleate giant cells, lymphocytes
- Michaelis-Gutmann bodies
– Round, concentric intracytoplasmic concretions within macrophages and between cells – Thought to represent defects in phagocytosis
20
Q
Polypoid Cystitis
A
• Results from mucosal irritation
- Common in patients with indwelling bladder catheter
• Mucosal appearance:
- Broad polypoid projections due to submucosal edema
• Can be confused with urothelial carcinoma
21
Q
Emphysematous Cystitis
A
•Inflammation associated with formation of air-filled spaces
22
Q
Cystitis Cystica
A
- Nests of transitional epithelium gown downward into lamina propria; may have central cystic spaces
- Can be seen in normal bladders, but also in the setting of inflammation and metaplasia
23
Q
Pyelonephritis
A
•Acute
-Most resolve
•Chronic
- Persistent/recurrent infections
- Due to abnormalities of the urinary tract
•Majority (>95%) are ascending infections from the bladder
– Hematogenous spread also occurs
• Most are bacterial infections:
– > 85% due to gram negative rods from the intestinal tract
– Most common: E.coli
– Others: Klebsiella species Proteus mirabilis Enterobacter species
– Less common: Staphylococci, Enterococcus
• Rare – Viral infections, mycobacteria, fungi
24
Q
Pyelonephritis - Nosocomial Infections
A
- Indwelling bladder catheters, patients on multiple antibiotics
- Most are due to E.coli
- Other organisms: Pseudomonas, Serratia, Staphylococcus epidermis, Candida albicans
25
Pyelonephritis -Hematogenous spread
* Associated with virulent organisms (Staphylococcus aureus, Salmonella)
* Predisposing factors:
- Ureteral obstruction
- debilitated patients
- immunosuppression
26
Pyelonephritis Predisposing factors to infection
* Urinary tract obstruction
* Instrumentation (catheters)
* Vesicoureteral reflux
* Pregnancy
– Incidence of bacteriuria doubles
– 20-40% patients with bacteriuria will develop symptomatic UTI
– 25% patients with UTI will develop pyelonephritis if untreated
* Pre-existing renal disease
* Diabetes Mellitus
– Instrumentation
– Generalized immunosuppression
– Damage to nerves can cause bladder dysfunction
– neurogenic bladder
• Immunosuppression, immunodeficiency
27
Pyelonephritis Pathophysiology
• Colonization of urethra then bladder
– Usually by intestinal flora (patient’s own fecal flora)
– Bacterial adhesion molecules (P-fimbriae) interact with receptors on urothelium
* Can promote migration to kidney, persistent infection or enhanced inflammatory response
* Females
– shorter urethra = increased incidence
* Multiplication of organisms in bladder – Outflow obstruction, bladder dysfunction --\> STASIS --\> bacterial growth
* Bacteria gain access to upper tract
– Instrumentation/catheterization
– Vesicoureteral reflux
– Valves fail to close tightly during micturition, allowing urine and bacteria to flow back into ureters
• Intrarenal reflux
– Urine (plus bacteria) refluxes from the renal pelvis back into the medulla
– Occurs at tips of compound (concave) papillae
– Upper and lower poles of the kidney
28
Pyelonephritis Factors preventing infection
* Active unidirectional peristalsis of ureters
* Ureterovesical valves
* Complete voiding of bladder
* Turbulent flow of urine exiting urethra
29
Acute Pyelonephritis
Clinical Presentation
• Fever, chills
– Present in about 2/3 cases
* Flank pain / CVA tenderness
* Constitutional symptoms
– Malaise, anorexia, vomiting, diarrhea, headache
• Symptoms of cystitis (bladder inflammation)
– Urgency, frequency, dysuria
• Note: Symptoms may be atypical in children, elderly and diabetics
30
Differential Diagnosis - Non-Renal
– Pneumonia
– Appendicitis
– Perforated intestine
– Splenic infarct
– Aortic dissection
– Acute pelvic inflammatory disease
31
Differential Diagnosis - Renal
– Infarct
– Renal vein thrombosis
– Obstructive uropathy
– Acute glomerulonephritis
– Stones
32
Acute Pyelonephritis Laboratory Findings
• Leukocytosis
– Increased WBC count, with “left shift”
• Urinalysis
– Pyuria (\>5 WBC’s/HPF in urine sediment)
– WBC casts
– Diagnostic of kidney disease
• Urine culture
– Usually \> 105 colony forming units per ml
• Positive blood culture
– 15-30% cases
– Increased risk in elderly, diabetics, immunosuppressed
– Usually represents spread from kidney to blood
33
Acute Pyelonephritis Pathologic findings (Gross)
– Focal abscesses, confluent wedge-shaped areas of suppuration, hemorrhage
– Late: May heal with a broad-based shallow scar
34
Acute Pyelonephritis Pathologic findings (Microscopic)
– Early: Patchy neutrophilic infiltrate in interstitium and within tubules (“neutrophil casts”), abscess formation, destruction of tubules
– Later: Mixed inflammatory infiltrate with neutrophils, lymphocytes, plasma cells – Glomeruli usually not involved
35
Acute Pyelonephritis Natural history
• Most cases follow a benign course
– Most recover with antibiotics and supportive care
• Adults with normal urinary tract
- almost never results in progressive disease
– Children with urinary tract abnormalities must be treated early to prevent progressive injury
• Bacteriuria may persist after therapy
– Follow up urinalysis and culture
36
Acute Pyelonephritis Complications
* Bacteremia/sepsis – 15-30%
* Papillary necrosis
– Necrosis of distal tips of medullary pyramids
– Usually seen in diabetics
• Pyonephrosis
– Exudate fills renal pelvis and ureters
– Seen in severe obstruction
• Perinephric abscess
– Extension of suppurative inflammation through renal capsule into the perinephric fat
37
Perinephritic Abscess - Acute Pyelonephritis
38
BK Polyomavirus
* Cause of acute viral pyelonephritis in renal allografts
* Cause of graft failure in 5% transplants
* Immunosuppression leads to activation of latent virus and inflammation of tubules and interstitium
* Renal biopsy gold standard for diagnosis:
a. Inflammation of tubules and interstitium, mostly composed of lymphocytes and plasma cells (unlike bacterial pyelonephritis)
b. Intranuclear viral inclusions visible in tubular epithelial cells
c. Virus can be detected by immunohistochemistry (SV-40 stain)
• Treatment: Reduce immunosuppression
39
Chronic Pyelonephritis
* Chronic disorder characterized by chronic tubulointerstitial inflammation and progressive scarring
* Causes:
– Chronic reflux (reflux nephropathy)
– Usually occurs in childhood
– Infection superimposed on congenital reflux
– Chronic obstruction
– Recurrent infection superimposed on obstruction
– May be unilateral or bilateral based on location of obstruction
• Abnormal urinary tract predisposes to repeated infections --\> progressive injury
40
Chronic Pyelonephritis Clinical Presentation
• Varied signs and symptoms, often vague or nonspecific
– Vague abdominal/flank discomfort, low-grade fever
– May have history of repeated UTI’s
– May present with ESRD without prior history
• Common cause of hypertension in children
– Due to chronic kidney disease
• Nocturia, polyuria
– Represents tubular dysfunction, loss of ability to concentrate urine
• May develop secondary focal segmental glomerulosclerosis (FSGS)
41
Chronic Pyelonephritis Pathologic Findings (Gross)
– Coarse, broad-based corticomedullary scar overlying blunted or deformed calyxes
– Scars irregularly distributed, most severe in upper and lower poles
– May be unilateral or bilateral; if bilateral usually asymmetric
42
Chronic Pyelonephritis
43
Chronic Pyelonephritis Pathologic Findings (Microscopic)
– Chronic interstitial inflammation with fibrosis
– Tubular atrophy and dilation with hyaline casts
– Glomeruli vary from normal to ischemic to obsolescent (secondary changes)
44
Xanthogranulomatous Pyelonephritis
* Special form of chronic pyelonephritis
* Associated with Proteus infections, obstruction
* Mixed inflammation with large amounts of foamy macrophages
* Can produce a mass lesion
– Can be mistaken for neoplasm
45
Staghorn Calculi
• Associated with chronic infections due to ureasplitting bacteria:
– Proteus
– Klebsiella
– Ureaplasma
• Struvite crystals --\> stones
– Large calculi fill pelvis, branch into collecting ducts
• Difficult to treat
46
Chronic Pyelonephritis Natural History
• If detected early
– Surgical correction of abnormal urinary tract allows normal function, prevents progressive scarring
• If detected at end stage
– No effective therapy to restore function
– Treat all infections to slow/prevent further injury
47
Allergic Interstitial Nephritis (AIN)
• Inflammatory disorder involving the interstitium and tubules
– Non-infectious
– Hypersensitivity reaction
• Associated with wide variety of drugs:
- Penicillins
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Other antibiotics
- cephalosporins, sulfonamides
- Diuretics
- thiazides
- Acetaminophen (rare cases)
48
Allergic Interstitial Nephritis Clinical Presentation
* Fever
* Skin rash
* Eosinophilia
* Acute kidney injury
* Abnormal liver chemistries
* Eosinophiluria
– Helpful when present, not very sensitive
• Onset of symptoms
- Usually after two weeks on drug (wide range)
• Not dose dependent!
49
Allergic Interstitial Nephritis Pathologic Features (Gross)
– Enlarged, swollen kidneys (due to edema)
50
Allergic Interstitial Nephritis Pathologic Features (Microscopic)
•Mixed inflammation within interstitium
-Eosinophils (especially in clusters), lymphocytes, PMN’s, plasma cells
* Tubular inflammation, tubular injury
* Early: Interstitial edema
* Late: Interstitial fibrosis, tubular atrophy
51
Allergic Interstitial Nephritis: Chronicity with Interstitial Fibrosis
52
Allergic Interstitial Nephritis Treatment
• Most important: Discontinue offending drug ASAP!!
– Continuing drug may lead to permanent injury due to scarring of interstitium and tubules
– Recovery of function may be delayed (weeks to months)
* Corticosteroids (Prednisone)
* Supportive care
53
Multiple Myeloma
* Multiple Myeloma (MM) – neoplastic disease of plasma cells
* Results in unchecked formation of monoclonal light chain immunoglobulins • These light chains detected in serum and urine
* 50% of patients with MM develop renal insufficiency
* Clinical presentations:
* Acute kidney injury
* Slow progressive rise in serum creatinine
* Glomerular dysfunction – proteinuria, hematuria
54
Multiple Myeloma Kidney Diseases
• Myeloma Cast nephropathy
– destructive tubulointerstitial disease
– Huge light chain burden, toxic to tubular epithelium
– Light chains complex to intratubular Tamm-Horsfall protein and form obstructive casts
– May have crystalline or “fractured” appearance
– Reactive inflammatory response --\>fibrosis/tubular atrophy
– Requires rapid treatment to lower light chain burden
* Others:
* Amyloidosis (AL type)
* Light chain deposition disease
* Acute tubular necrosis
55
Myeloma Cast Nephropathy
56
Myeloma Cast Nephropathy
57
Myeloma Cast Nephropathy
