pathology of prostate gland

peripheral glands (peripheral zone) therefore palpable on examination

carcinomas arise from

central glands (central zone), non palpable and more likely to produce URINARY obstruction (obstructs the urethra) earlier than carcinoma

nodular hyperplasia arises

1) INNER epithelial cells --> under androgenic control and secrete prostate specific antigen (PAS)
2) OUTER/underlying basal cells --> lost in carcinoma (malignancy)

glands bilayered

- either acute (UTI: e.coli) or chronic
- chronic abacterial
- granulomatous

prostatitis causes

aka nodular hyperplasia of prostate
- ages 40 and above, a lot around 60, mainly around 80 y/o
- urinary frequency, nocturia, difficulty in starting/stopping urine, overflow dribbling and dysuria

benign prostatic hyperplasia presentation

hyperplasia of prostatic stromal/epithelial cells = nodules around periutethral region of prostate
- role of androgens (inner epithelia regulated by it)
- influence cell proliferation and apoptosis

BPH aetiopathogenesis

1. medical:
alpha blockers - A1 receptors decreasing muscle tone
or
inhibit synthesis of DHT: inhibitors of 5-alpha-reductase shrinks prostate
2. surgical
resection of prostate

BPH treatment

A. central portion separated by urethral slit = obstruction
B. nodules formation
C. dual cell population: inner columnar epithelial and outer flattened basal cells (not lost)

describe images

- occurs in same age population but detected later as the obstruciton occurs later on
- glands in peripheral zone
- symptoms are same of BPH

adenocarcinoma of prostate

- OSTEOBLASTIC metastasis especially in vertebra

adenocarcinoma of prostate metastasis

prostate specific antigen
- can occur in cancer elevated levels

PSA

prostate carcinoma has perineural invasion of malignant glands

adenocarcinoma of prostate invasion

- poor differentiated = less glands, forms sheets of malignant cells + irregular branches
- lower grade cancer = presence of crystalloids around glands

GLEASON GRADING

A. well differentiated = lower gleason score, glands contain crystalloids around
B. variably sized, moderately differentiated, still forming glands tho
C. no gland formation, high grade cancer

c

- local expansion = periprostatic tissue
- metastasis = lympatics + blood

adenocarcinoma spread besides bone

most common is UROTHELIAL (transitional) tumors
CIS (not spreading but very dangerous)

bladder neoplasms types

hematuria, irritiative symptoms, obstructive symptoms,

bladder cancer features

- smokers
- exposure to arylamines industrial arylamines
- schistosoma hematobium
- long term use of analgesics
- exposure to cyclophosphamide (immunosuppressant)
- preior exposure to bladder radiation

bladder cancer causes

1) non invasive papillary tumor of bladder
2) flat non invasive or invasive carcinoma aka carcinoma is situ CIS (basement membrane invasion = malignancy)
- invasion to lamina propria and MUSCULARIS PROPRIA = worse prognosis

precursors to invasive UROTHELIAL carcinoma

high grade papillary urothelial carcinoma (atypia)

- if non-muscle invasive cancer = treatment is prevention to MIBC so transurethral resection of blasser
- if MICB = radial cystectomy

treatment of urinary bladder cancer

- metabolic factors = obesity
- beverage consumption - caffeine/alcohol beneficial as they reduce androgen
- intake of vitamin A beta carotene is beneficial, reduce Vitamin C

modifiable risks of BPH

- CV risk
- neurologic factors (detrusor function and stability)
- diabetes - decrease bladder sensitivity, detrusor contractility, incomplete emptying, polyuria

conditions exacerbating LUTS/BPH

1) mediated by dihydrotestosterone produced by 5 alpha reductase conversion from testosterone. Inhibition of 5alpha = treat overflow incontinence
2) muscle tone prostate mediated by alpha 1 adrenergic receptors

pathophysiology of BPH

upreglated in BPH
blocks alpha1 receptors in internal sphincter --> relax smooth muscle of bladder --> increase urethral flow = helps in overflow incontinence
ends with zosins

alpha 1 adrenergic receptors antagonist

alpha 1 receptor antagonist
useful in BPH
postural hypotension/dizziness/headache (occurs in alpha blockers), sexual adverse effects
do not use with viagra (PDE-5) sildenafil/talanafil
do not use during cataract surgery

tamzulosin

e.g. tadalafin/sidalafil
used in BPH + erectile dysfunction
do not use with alpha 1 blocker or postural hypotension increases

PDE 5 inhibitors

- blocks conversion b/w testosterone to dihydrotestosterone
- effective in LUTS rather than in BPH (prevention cure)
- reduce prostate size (shrinks) - PSA used to measure prostate volume
- can be used in hair loss for men
e.g dutasteride = do not use in PREGNANCY (accidental)

5 alpha reductase inhibitors

1) anticholinergic agents = ach muscarinic atagonists - increase bladder size + decrease contraction (dry mouth, constipation...)
2) beta 3 adrenergic agonists = stimulate detrusor to promote relaxation + less side effects

overactive bladder (urge continence)

1) alpha1 antagonists + 5 alpha reductase (dutasteride + tasmulosin) = overflow incontinence improved + shrinks prostate = DUODART)
2) beta 3 agonists + alpha 1 blockers = OAB + relaxation muscles but side effects

combination therapy

acts like 5 alpha reductase inhibitors + anti inflammatory

herbal saw palmetto

herbal

hypoxis rooperi

herbal

pygeum africanum

e.g. goserelin
gonadotrophin releasing hormone analog, increase of FSH and LH to decrease testosterone
- QT prolongation effects

androgen deprivation therapy

more than 25mL

size prostate to be enlarged

- acute urinary retention
- increase UTI risk
- bladder stones
- formation of diverticuli (no epmtying so the bladder expands, more pressure, herniation)
- renal damage

complications of BPH

- urine retention
- UTI recurrency
- stones
- diverticuli

when to go for surgery in BPH

- start on alpha blockers (stop priot to surgery)
- do US KUB
- if high bladder volume
- insert catheter
- start on duodart (combination alpha 1 blocker and 5-alpha-reductase)
- if after removing catheter, still high then think surgery

steps for BPH

- stress incontinence: stress situation like lifting, squeezing, sneezing = leak (occurs in pregnancy, pelvic floor therapy needed)
- urge incontinence: patients with OAB (detrusor contracted) --> give medication (anticholingergic/beta 3) or botox to paralyze detrusor
- mix of both

types of incontinence

below 15ml/second is LOW

uro-flow study Q max value

- most common benign renal tumor
- cannot metastasize
- papillomatous structures
- do not differ from low grade papillary renal cell CARCINOMA
- both contain 7 and 17 trisomies
- treat like its cancer

renal papillary adenoma

- benign tumor composed of vessels, fat and muscle
- found in people with tuberous sclerosis (loss of function in TSC1 and 2)
- can hemorrhage

angiomyolipoma

- condition leading to angiomyolipoma (sometimes multiple lesions)
- triangular lesions in brain
- ash leaf macule on skin
- angiofibroma on skin (bumps)

tuberous sclerosis

angiomyolipoma
vessels, fat, muscle containing spindle cells

renal papillary adenoma papillary architecture

aka benign oxophilic adenoma
- encapsulated, tan, mohogany brown with central scar
- contains oncocytic cells (eosinophilic)

oncocytoma

oncocytoma

- most common malignant tumor
- arise from tubular epithelium = renal adenocarcinomas

renal cell carcinoma

- smoking, obesity, hypertension, renal failure, tuberous sclerosis
- inherited: sporadic
1. von hippellindau: hemangioblastomas, renal cysts and RCC
2. hereditary clear cell carcinoma
3. hereditary papillary carcinoma

epidemiology of RCC

if present: costovertebral pain, palpable mass and hematuria
- metastasize widely (lungs ad bones)

renal cell carcinoma diagnostic features

- common: clear cell carcinoma
- papillary carcinoma (7,17 trisomies)
- chromophobe renal - good prognosis + raisinoid nuclei
- collecting duct (bellini) carcinoma - medullary location

types of RCC

clear cell carcinoma

A. clear cell carcinoma
B. papillary
C. chromophobe = raisinoid nuclei

collecting duct (bellini) carcinoma - rare + aggressive form

usually w/ immunotherapy + tyrosine kinase inhibitors

treatment of RCC

aka wilms tumor
-affects children
- lobulated lesion can be seen
- involves both kidneys

nephroblastoma

- tumor suppressor gene in kidney and gonads
- wilms tumor can have mutation in this gene

WT 1 gene

- WAGR syndrome: aniridia, genital anomalies, retardation
- Denys drash syndrome: dysgenesis gonads, renal failure
- BWS syndrome: hemihypertrophy, omphalocele.

nephroblastoma associations

1) blastemal component (purple cells)
2) epithelial = primitive tubules
3) mesenchymal

triphasic histology of nephroblastoma

A. 3 components of nephroblastoma
B. anaplasia nephroblastoma

collecting duct, as reabsoprtion is load dependent

region where calculi most likely to form

occur in collecting duct, load dependent --> depends on saturation and pH

precipitation location

urine saturation --> supersaturation --> nucleation of crystals --> aggregation = stone formation

steps to stone formation

promoters: high urinary excretion of calcium, oxalate and urate
inhibitors: high rate of citrate excretion, potassium and magnesium as they dilute urine

promoters and inhibitors of stones

- male gender
- low fluid intake
- high salt intake (na)

general risk factors for stones

- iodiopathic
- hyperparathyroidism
- hypercalcemia
- supplements

hypercalciuria and stones

1)enteric hyperoxaluria: short bowel, fatty acids bind to calcium and oxalate is free to be reabsorbed in gut, or oxalate is not secreted through colon therefore enters urine (associated w/chrons and celiac disease)
ileum resection: malabosprtion of bile salts, increases permeability to oxalate
2) primary hyperoxaluria
genetic disorders PH1 and 2

high urinary oxalate

- hypokalemia
- chronic acidosis
- distal renal tubular acidosis - genetic loss of bicarbonate

hypocitraturia

metabolized to oxalate or uric acid
decreases pH

high animal protein intake in stones

- composed: potassium, ammonium, phosphate
- due to UTI urease +ve e.g. proteus

struvite stones

- increase fluid intake - nocturia
- decrease salt use
- decrease animal products
- decrease vit c supplement and calcium

principles of management stones

- recurrent stones: give thiazide diuretics that reduce calcium excretion in urine and promote hyperkalemia
- hypocitraturia: potassium citrate supplements
- enteric hyperoxaluria: stop eating oxalate food
- primary hyperoxaluria: pyridozine supplements

specific management stones

calcium oxalate

low pH stones

calcium phosphate

high pH stone