Download Pathology – Lecture 44: Prostatitis and BPH 11/29/12 Prostatitis

Pathology – Lecture 44: Prostatitis and BPH
11/29/12
Prostatitis
 Definition – infection or inflammation of the prostate
 Epidemiology
o Most common urological diagnosis in men < 50 yo
 Pathology
o 2 histological patterns
 Acute inflammation
 Characterized by the presence of neutrophils w/in the lumen of acini,
glandular epithelium, and in the stroma
 Chronic inflammation
 Characterized by a lymphocytic infiltrate in the stroma
 Classification
o NIH – 4 categories
 Category I or “acute bacterial prostatitis”
 (acute infection of the prostatic gland);
 Category II or “chronic bacterial prostatitis”
 (chronic infection of the prostate gland);
 Category III or “chronic pelvic pain syndrome” (CPPS)
 (genitourinary pain in the absence of pathogenic bacteria localized to the
prostate gland);
 Categories IIIA and IIIB (chronic nonbacterial prostatitis and prodtadynia) are
the most frequent of prostatitis syndromes
 Category IV or “asymptomatic inflammatory prostatitis”
 (presence of inflammatory reaction in the prostate but with no clinical
manifestations)
 Lab Evaluation of the Lower Urinary Tract
o Meares-Stamey test
 Method to distinguish urethral, bladder, and prostate infections
 4 specimens
 Voided bladder 1 (VB1) – first 10 mL of urine
o = urethritis
 VB2 – midstream specimen
o = expressed prostatic secretion (EPS)
 VB3 – first 10 mL or urine after massaging the prostate
o Includes any EPS trapped in prostatic urethra
o Culture and microscopy of this sediment
 Interpretation
 Acute bacterial prostatitis
o Prostatic fluid is clinically purulent, w/ systemic signs of infection, and
bacterial are cultured from fluid
 Chronic bacterial prostatitis
o Pathogenic bacteria are recovered in large numbers from a purulent
prostatic fluid in absence of UTI or significant systemic signs
 Nonbacterial prostatitis
o Significant numbers of bacteria cannon be cultured; fluid consistenctly
reveals microscopic purulence
 Prostadynia
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o Diagnosed in the remaining pts who had persistent pain and voiding
complaints, but no significant bacteria or purulence in the prostatic
fluid
Cat 1: Acute Bacterial Prostatits
o Definition
 Severe systemic infection
 Arise spontaneously (90%) or after UG tract manipulations
o Etiology
 Enterobacteriaceae family of gram-negatives
 E. coli – 65-80%
 P. aeruginosa, Serratia spp., Klebsiella spp., and Enterobacter aerogenes
o Pathogenesis
 Infected urine refluxes into the ejaculatory and prostatic ducts
 Ascending urethral infection
 In younger men, may occur following sex
 Instrumentation and prolonged catheterization
 Direct invasion or lymphogenous spread from the rectum
 Direct hematogenous infection
o Pathology
 Grossly
 Prostate is enlarged and soft
 Micro
 Neutrophils
 ed prostatic secretions
o Clinical Presentation
 Acute illness w/ moderate to severe fever, chills, LBP and GU pain
 Pain in the perineum, and maybe at the tip of the penis or testes
 Possible painful ejaculation
 Other Sxs: urinary frequency and urgency, nocturia, dysuria, and malaise; arthralgia
and myalgia
 Obstructive voiding
 Rectal palpation – enlarged, tender, swollen prostate
o Labs
 Urinalysis
 Pyuria (> 10 leukocytes/hpf)
 Culture reveals bacteria
 Prostatic secretions
 Exam of EPS  large #s of WBCs and bacteria
 Blood cultures
 Serum PSA levels – significantly elevated
o Diagnosis
 Based mainly on clinical findings, in assoc. w/ positive UA and urine culture
o Complications
 Prostatic abscess (needs surgery)
Cat 2: Chronic Bacterial Prostatitis
o Definition
 Bacterial growth in culture of the EPS, semen, or postmassage urine specimen
o Clinical Presentation
 Most important diagnostic clue is hx of relapsing UTIs + genital Sxs
 Pelvic pain, dysuria, dribbling
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 Rectal exam can be normal
o Labs
 Numerous leukocytes and pathogenic bacteria in EPS and VB3
 > 10 WBCs/hpf
  PSA
o Pathology
 Localized process involving a small # of ducts or acini
 Stroma infiltrated in mix of lymphocytes, plasma cells, and histiocytes
 Glands are distended, filled w/ secretion & mixed inflammatory cells (neutrophils)
o Causes
 Usu. a single pathogene; E. coli or gram-negatives (Klebsiella spp.)
o Diagnosis
 Standard is the 4-glass test bacterial localization study
 Biopsy is contraindicated (may  urosepsis)
o Pathogenesis
 A sequela of acute bacterial prostatitis
Cat 3: Chronic Pelvic Pain Syndrome
o Definition
 Unexplained GU pain in men
 Assoc. w/ irritative voiding Sxs in the absence of pyuria and bacteriuria
o Subcategories IIIA and IIIB
 IIIA – nonbacterial prostatitis
 GY pain/discomfort combined w/ the presence of inflammation (leukocytes)
in EPS and VB3 compared w/ VB1 and VB2, but w/ negative cultures
 Presentation
o No history of recurrent UTIs; absence of pathogenic bacteria
o Pain/discomfort for at least 3 months in pelvic region
o Back pain and pain w/ ejaculation
o Voiding Sxs
o Excessive leukocytosis in EPS and VB3
 IIIB – prostatodynia
 Isolated GU discomfort
 No inflammation and negative cultures
o Labs
 Repetitive cultures are negative
o Pathogenesis
 Unknown definitive etiology
 PCR shows presence of bacterial rRNA genes
 Immune-mediated
 Chemically-triggered infection
 Neuropathic pain
o Diagnosis – 4-glass test
o Treatment
 Broad-spectrum ABX
Cat 4: Asymptomatic Inflammatory Prostatitis
o Definition
 Doesn’t cause Sxs
 Presence of inflammation and/or infection in prostate specific specimens
o Diagnosis is made incidentally
o Epidemiology
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Common findings in pts w/ BPH w/ no Sxs of prostatitis
Benign Prostatic Hyperplasia
 Definition
o Characterized by hyperplasia of prostate stromal and glandular epithelial cells  formation
of large discrete nodules in the periurethral region of the prostate
o  enlargement of the prostate
  nodules compress and narrow the urethral canal to cause urethral obstruction
o Currently considered a normal part of aging in men
o Hormonally dependent on testosterone and DHT production
 Pathology
o Normal Prostate
 Compound tubuloalveolar gland w/ exocrine fxn that secretes fluid that is 15% of
the ejaculate (secretion serves as a volume expanding vehicle for sperm)
 Adult gland has 4 regions
 Peripheral zone
o Most prostate carcinomas
 Central zone
 Transitional zone
o Most BPH
 Periurethral gland region
 BPH
o A hyperplastic process that originates in the transition zone
 Early nodules of stromal cells and later mainly epithelial nodules
o Gross findings
 Fibromuscular nodules are small, pale gray, tough and solid
 Glandular nodules are large, yellow-pink, microcystic and soft
 Lined by two layers of epithelial cells
o Phases of natural history
 Growth of each new nodules is generally slow
o Prostate size
 Doesn’t correlate w/ degree of obstruction
 Sometimes, mainly growth of periurethral
nodules at the bladder neck gives rise to the “middle lobe enlargement”
 The bladder’s response to obstruction
o Adaptive obstruction-induced changes in bladder function
o A/b 1/3rd of men have significant voiding dysfunction after surgical relief of obstruction
o Changes
 Range from detrusor hypertrophy to ed detrusor contractility, and terminating in
bladder failure
 Detrusor hypertrophy
 Partial outflow obstruction initially results in ed intravesical pressure
 Trabeculation of the bladder inner wall
o Thick strings of intertwined muscle fibers
 Detrusor muscle instability
 Hypertrophic muscle becomes hyperactive and contracts inappropriately during
the filling stage  frequency and urgency
 ed detrusor contractility
 Chronic retention of urine  ed detrusor contractility and a thin-walled, flaccid
bladder
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o Significant residual urine
o  force of urine stream, hesitancy
 Acute urinary retention
 Upper urinary tract functional and anatomic damage occurs
 Renal failure, UTI, and renal calculi are complications
Pathophysiology
o 2 factors in bladder outlet obstruction
  intrinsic prostate tension due to contracting prostate stromal muscle cells and/or
extrinsic tension on the BPH prostate mass by a contracting prostate capsule
o -adrenergic receptor blockers (i.e. terazosin) alleviate Sxs and improves peak urine flow rate
in men w/ BPH
Clinical Presentation
o Bladder outlet obstruction (BOO)
o Lower urinary tract symptoms (LUTS) or prostatism
 Clinical manifestations
 Constricts flow of urine 
o Urinary frequency
o Urgency
o Hesitancy
o Incomplete bladder emptying
o Straining
o Decreased force of stream
o Dribbling
 Complex is nonspecific and can be caused by neurogenic bladder, bladder cancer,
cystitis, bladder stones, prostatitis, prostate cancer, and urethral stricture
o Physical Examination
 Digital rectal examination (DRE)
 Transrectal U/S
 Percussion and palpation of suprapubic area reveals bladder distension
Natural History
o Becomes much more clinically noticeable as the man ages
o Not all the nodules are in the same phase of development
o Usu. progressive once it’s developed
Etiology
o ed proliferation assoc. w/ ed apoptotic rate
 Proliferation is higher and apoptosis is lower in BPH tissues
  ornithine decarboxylase (ODC) activity
  p38 mitogen-activated protein kinase (MAPK) – a marker of proliferation
  anti-apoptotic factor bcl-2
o Dihydrotestosterone (DHT)
 Hyperplasia seems to be in response to androgens, mainly DHT
 Formed in the prostate by conversion from testosterone via 5-reductase
 Located in stromal cells
 DHT has a higher affinity for AR than testosterone and mediates production of growth
factors, including FGF-7
Treatment
o Alpha blockers
o 5-reductase inhibitors
Complications
o Acute urinary retention, recurrent UITs, gross hematuria, bladder calculi, and hydronephrosis
and renal failure or uremia (rare)