Week 2 - Prostate, Renal, Urinary Tract Flashcards
Outline urinary tract infections (UTIs).
• Urethritis, cystitis, prostatitis, pyelonephritis,
• 90% by Escherichia coli*, recurrence (40%).
- Recurrent UTIs common.
• Uropathogenic strains (UPEC). P fimbriae or pili - bind to urothelium.
- Caused by uropathogenic strains of E. coli - P fimbriae or pili specialised in these bacteria bind to urothelium - grow in urinary tract.
• Colonise colon spread to urinary tract.
- Due to close anatomic location.
• Staph., Saprophyticus, Proteus, Klebs., Enterococci, Ureaplasma - Rare.
- Staph, Saprophyticus ~5%.
- Other bacteria ~5%.
• Commonest entry point through urethra but can also enter through blood supply (systemic spread - less common).
Identify the clinical features of UTIs.
• Females, anatomy, sexual activity, urinary tract abnormality/obstructions e.g. stones, tumours - all predispose to infections.
- Females more common due to short urethra and closer proximity to colon.
• Clinically presents as dysuria, low grade fever (or no fever), frequency, urgency.
• Flank pain, high fever - pyelonephritis.
- When present with high fever and flank pain - more typical of pyelonephritis.
• Complications - E. coli septicaemia* endotoxins → DIC*, prostatitis, prostatic abscess.
- E. coli septicaemia common.
- Endotoxin raised causing DIC.
Outline the diagnosis of UTIs.
• Blood - leukocytosis - neutrophilia.
• Midstream clean catch urine specimen*
- Urine usually cloudy and see RBCs after centrifugation.
• Dipstick - leukocyte esterase and nitrite +ve - suggestive of infection.
- Leukocyte esterase only present in neutrophils so if the patient has lymphocytes, it won’t show up on the dipstick.
• Urine - pyuria, neutrophils, bacteria.
- Urine dipstick and MCS.
• MacConkey agar* selective, indicator media.
- 24h, 37˚C, aerobic environment, pink colony (lactose ferment → acid → pH indicator).
• Lactose in agar plate with pH indicators.
• E. coli forms pink colonies - ferment the lactose and release acid → pH indicators in the medium turn bright pink.
- Beta-haemolytic on blood agar.
Microscopy gram stain:
• Gram negative (pink) Bacilli, lactose fermenting.
• Also Enterococci.. and Klebsiella ferment lactose.
- Difficult to distinguish between bacteria - many tests to confirm/differentiate bacteria.
• Further tests to confirm - E. coli → urease -ve (unlike Klebsiella and Proteus +ve).
- E. coli urease negative and Klebsiella and Proteus urease positive.
Describe the structure and function of the prostate.
• Periurethral, Fibromuscular gland.
• Function - semen, acid phosphatase. Sperm nutrition.
- Delivering semen and protecting the sperm with its nutrition. Important substance is acid phosphatase and prostate specific antigen.
• Hormone response - androgens, testosterone.
- Prostate responds to hormones - proliferative hormones.
• Prostatitis (infection/inflammation), BPH and cancer (most important clinically).
- Major disorders.
• Central zone - BPH.
- Central zone of prostate involved in BPH. Peripheral zone in cancer.
• Peripheral zone - cancer.
- Transitional zone in periuretheral area is the commonest site of BPH.
- Cancer usually located in peripheral zone - importance of DRE - can palpate hard gritty stoney swelling of cancer.
- BPH smooth firm enlargement.
Describe the normal prostate histology.
- Fibromuscular stroma.
• Muscles. - Glands double layer epithelium.
• Basal layer - flattened epithelium.
• Columnar epithelium - secretory epithelium - secrete major component of semen. - Secretions (corpora amylaceae).
• Protein aggregates - part of semen secretions.
Identify the disorders of the prostate.
- Inflammations - infections - prostatitis.
- Benign Prostatic Hyperplasia*
• Starts in central periuretheral area, benign tumour, smooth, encapsulated - enlarges into the bladder because this is the only place that the gland can easily break through (the rest of the area is fibromuscular - hard). Grows into bladder obstructing urinary opening (internal meatus). - Neoplasms - prostatic carcinoma*
• Peripheral zone posteriorly - hard gritty tumours → DRE.
Outline the 4 types of prostatitis.
• Inflammation, oedema, rectal pain, obstruction/dysuria.
- Pain and discomfort in prostatic area/rectum, obstruction to urinary flow - patient tries to pass urine but causes pain due to inflammation.
4 major types:
• Acute suppurative prostatitis 5%
- E. coli, rarely Staph or N. gonorrhoeae.
- 5% of cases (not common) commonly due to E. coli.
• Chronic non bacterial AKA chronic pelvic pain sy.
- 90% chronic inflammation, symptoms, no pathogens.
- Most common.
• Asymptomatic inflammatory prostatitis.
- Only WBC, no symptoms, no pathogens.
- Rare - not very common.
• Granulomatous prostatitis.
- BPH, infarction, post TURP, idiopathic, TB or allergic (eosinophilic).
- Usually post surgery or idiopathic, TB, allergic - rare.
Describe the diagnosis and morphology of prostatitis.
Diagnosis:
• Fluid examination after prostatic massage.
• Needle aspiration study of prostatic tissue (fine needle aspiration biopsy).
Morphology:
• Microscopy - oedema and plenty of inflammatory cells in between the gland.
Outline benign prostatic hypertrophy (BPH).
• Non-neoplastic, androgen → hyperplasia. Castration → no BPH.
- Non-neoplastic, androgen induced hyperplasia (excess hormones or excess response to the hormones) - hyperplasia following androgen stimulation.
- Prostatic cancer and prostatic hyperplasia in old age where complete therapy is contraindicated → patients undergo castration - reduces BPH symptoms.
• Testosterone → DHT → hyperplasia.
- Testosterone gets converted to DHT (through the enzyme 5α reductase) → acts on nucleus to release growth factors → growth factors stimulate cells to divide → hyperplasia.
- Common, 75% of men 70-80 years. Only few symptomatic.
- Involves periurethral transitional zone.
Morphology:
• Nodular hyperplasia of glands and stroma (like in breast, thyroid etc.)
- Hormone induced hyperplasia.
• Stromal and gland hyperplasia. Cystic glands, secretions, double layer maintained.
- Glands are cystic with secretions and maintaining the normal double layer epithelium.
• BPH is NOT a precursor to carcinoma.
- Patients may have BPH and prostatic cancer but BPH is not a known precursor of carcinoma.
Describe the morphology of BPH.
Gross: grey white, nodular hyperplasia, periuretheral zone.
Microscopy: hyperplastic cystic glands, normal double layer epithelium.
Gross:
• Periuretheral zone markedly enlarged with nodules.
• Cut section - white nodules compressing urethra.
• Well demarcated.
• Enlarges into the bladder - explains all the clinical features. When patients try to force urine → blocks more.
Microscopy:
• Nodules of hyperplastic glands that are cystic and with secretions.
• Hyperview - plenty of glands, stroma outside, double layer epithelium.
• Double layer important microscopically because in cancer, it will be a single layer.
Identify the complications of BPH.
• Enlarged prostate.
- Enlarged prostate with the formation of the median lobe ball valve. Median lobe of prostate becomes a ball obstructing the opening.
- Marked thickening of the bladder wall.
- Prominent mucosal folds.
- Retention of urine leading to recurrent infections - inflamed mucosa, stone.
• Median lobe - ball valve*
- Urinary obstruction.
- Urine retention
- Inflammation/infections
- Hypertrophy of wall.
- Mucosal trabeculations (due to hypertrophy of bladder wall).
- Urolithiasis - stones (due to retention of urine - usually triple phosphate stones).
Outline prostate cancer.
• Adenocarcinoma, most common male cancer, elderly (>50y).
- Most common male cancer, significantly high compared to all other cancers.
- Although cases of prostate cancer are high, death due to cancer is low.
• But second common cause of cancer death in males (next to lung).
• Many prostatic carcinomas are small and clinically insignificant (or do not progress).
• If tested, seen in many elderly dying of other causes* (incidental cancer).
- Find many prostate cancers which were not identified before.
• But some are rapidly fatal, no specific test to detect early*
• Population screening of PSA - controversial - now discouraged*
- Only available test is PSA but this is controversial. Lack of specificity.
• % of free PSA to total PSA is lower in men with prostate cancer.
Describe the morphology of prostate cancer.
Gross:
- Irregular, stony hard (hard, gritty/stoney)
- Peripheral/posterior.
- Common in the posterior part/peripheral zone - near rectum → DRE. BPH grows anteriorly into bladder, cancer grows posteriorly.
- Hard gritty tumours without much haemorrhage or necrosis (unlike other cancers).
- When it spreads - starts as multiple nodules initially within capsule → later spreading out.
- Peripheral zone → invades capsule of prostate to extend beyond it to the surrounding structures such as the seminal vesicle.
Explain the aetiopathogenesis of prostate cancer.
• Aetiology - ?Androgens, genes (ETS, PTEN) and ?env/diet (Not BPH).
- Like many cancers, unknown - androgens have been implicated.
- Castration decreases swelling/tumour growth → androgen dependent.
- Recent discovery of mutations in tumour suppressor genes - ETS, PTEN → provided more understanding.
- Environmental and dietary factors have also been implicated but not proven.
- BPH is not a known precursor of cancer although both disorders occur in older age.
• Patients (54%) lacking both PTEN and ETV had ‘good prognosis’ (85.5% alive at 11 years)* - localised cancer without killing
- Significant proportion of prostatic cancers do not kill.
- Pathogenesis - dysplasia → PIN → cancer.
- Same as other epithelial malignancies.
- Initial irritation → dysplasia → mutations → transforming into cancer but localised - in situ cancer (prostatic intraepithelial neoplasia - PIN) → later progresses to cancer.
- Normal (double layered epithelium) → PIN (mutations and cancer initially remain within the gland ) → Invasion → Metastasis.
Outline prostate specific antigen (PSA).
• PSA* proteolytic enzyme, liquefies semen. Not cancer specific. Normal serum PSA <4.0ng/L. Increase in prostate damage/malignancy.
- Prostate specific antigen - most commonly used diagnostic marker.
- Proteolytic enzyme - functions as a liquefier.
- Not cancer specific - part of normal prostate. Simple prostatic massage can increase PSA levels.
• Lower in non malignant conditions but significant overlap*
- Issue of using PSA as a screening test.
Describe prostate cancer microscopy.
- Pleomorphic cells.
- Single layer glands.
- No secretions.
• Microscopic features very characteristic unlike other cancers.
• Normal - irregular gland with papillary projections, double layer (inner columnar cells and outer flat cells) with secretions.
• Cancer - more irregular looking (pleomorphic cells), single layered glands.
• Hyperview
- Normal - regular arrangement of nuclei at the base, functional.
- Cancer - irregular nuclei, clustering, single layer glands/irregular clusters, no flattened basal cells, non-functional (no vacuolations).
Outline the Gleason scoring for prostate cancer.
• Biopsy microscopy study.
• 2 prominent areas.
• Add the values (2-10 max.).
E.g. 3 + 4 = 7
- Gleason scoring based on 2 prominent areas in a microscopic slide.
- Look under microscope, check all areas and pick 2 common areas - grade each area and add the values.
- Method used to add more accuracy.
- Low grade - single layer cell, cancerous glands in one place.
- Glands more spaced, more irregular, infiltrating away.
- Unusual cells without any forming glands.
• Limitations - depends on accuracy of biopsy.
Prostate cancer summary.
• Staging: stage 1 (90% 5 year survival) to stage 4 (10% survival).
- Stage 1 - within one area in the gland.
- Stage 2 - spread out.
- Stage 3 - touching the capsule.
- Stage 4 - beyond the capsule spread (poor prognosis).
• Adenocarcinoma, commonest male cancer.
• Two clinical types - good and bad prognosis.
• Many cancers are small, non palpable (DRE can miss), asymptomatic, only discovered on needle biopsy following raised PSA level*
- Many of these cancer usually don’t progress. Controversy over whether to start invasive treatment or just monitor PSA levels.
• 20-40% of localised prostate cancer have normal PSA value.
• PSA is useful but imperfect marker*
- Not cancer specific.
• Progressive increase in PSA is more useful in monitoring.
- Unlike benign conditions, PSA rapidly increases when the cancer is spreading.
• Low grade, localised cancers best managed by wait and watch.
- As many of them do not progress.
Outline lithiasis.
Urolithiasis = stone outside kidney. Nephrolithiasis = stone within kidney.
• Calcium stones (80%): oxalate/phosphate/urate salts (alkaline urine). Stone first, obstruction later. Small, spiky, haemorrhage.
- Hypercalciuria (familial 54%), increased gut absorption. Commonest aetiology is hypercalcuria (mostly familial) where there is increased gut absorption and increased excretion in the urine. (Serum Ca2+ is normal).
- Rarely defective tubular reabsorption of Ca+ (AKA renal hypercalciuria).
- UTI, common risk factor, hyperparathyroidism rare (<10%).
• Commonest clinically are calcium stones - oxalate, phosphate or urate salts of calcium. Usually form in alkaline urine. Small (1-3mm), spiky, cause haemorrhage.
• Struvite stones (15%): magnesium ammonium phosphate (triple phosphate stones). Staghorn stone - obstruction first, stone later.
- Chronic UTI with gram negative rods (split urea) pH > 7
- Urea splitting Proteus, Klebsiella etc. (not E. coli).
• Obstruction to urine flow and secondary infection occurs first.
• Uric acid stones (6% - rare):
- pH <5.5, high protein (meats), malignancy, gout (25%) - causes.
• Cystine stones (2%): genetic - failure of reabsorption.
Outline urinary colic - calcium oxalate.
• Clinically caused by the small stones of the calcium group. Pain starts in the loin and radiates to the front.
• Unilateral, small 1-3mm, Ca oxalate stones.
• Passage causing paroxysmal, intense colicky pain in the loin, radiation to anterior (renal or ureteral ‘colic’) - ‘writhing in pain’ + haematuria (no casts).
- Stone formed in renal pelvis → pass through ureter → get stuck in the upper, middle or lower end.
- Spiky stones cause severe pain, spasmodic, intense - writhing pain.
Clinical symptoms based on level of obstruction:
1. Pelvis/ureteropelvic junction - deep flank pain, no radiation. Stretching of renal capsule.
• Rare. No radiation due to stretching of renal pelvis capsule.
2. Ureter - acute, severe, colicky pain in the flank, radiation to the testes/vulva. Nausea/vomiting. Most common clinically - ureteric obstruction.
a. Upper ureter - DDx cholecystitis.
b. Middle - DDx appendicitis.
c. Distal ureter - DDx pelvic inflammatory disease
3. Uretrovesical junction - irritative voiding/dysuria (characteristic feature).
• Pain in tip of penis/vulva.
Outline Staghorn/triple phosphate/struvite stones.
• 15% of urolithiasis. Stone forms in Alk. pH >7.
• Obstruction → urine retention → infection → stone form.
- Obstruction due to some other cause happens first → secondary infection by urea splitting organism → causes stone formation - stones usually huge and fill the spaces available as the initial obstruction causes hydronephrosis (dilation).
- Usually not with severe pain like the calcium oxalate.
• Proteus, pseudomonas etc. Urea → ammonia (alk. phos).
• Large stone molds to pelvis and calyceal system (staghorn shape).
• Triple (struvite) phos. - magnesium ammonium phosphate.
• Chronic irritation, sq metaplasia and sq ca. rarely occur.
Causes and complications:
• Ureteral stricture, infection, sepsis.
• Obstruction → hydronephrosis* → CRF.
• Pyelonephritis, abscess.
- Secondary infection spreads to kidney - pyelonephritis.
- Perirenal abscess.
Outline hydronephrosis.
Any obstruction leading to dilation of renal pelvis and calyces with atrophy of parenchyma.
• Dilation of renal pelvis and calyces with atrophy of parenchyma. Secondary to obstruction*
- Congenital - ureteric atresia, kinks, torsion etc.
- Acquired - calculi, tumours, inflammation, stricture, foreign body, neurogenic, pregnancy. (Acquired most common).
Stone can cause hydronephrosis and hydronephrosis can cause stones.
• Bilateral hydronephrosis - obstruction at or below the bladder (usually partial).
• Dilation of ureter → hydroureter.
• Bilateral partial → polyuria.
- Bilateral partial hydroureters can cause polyuria due to defective tubular function.
• Unilateral complete/partial → may be asymptomatic (one of the kidneys is still functioning).
Complications:
• Infection, lithiasis (triple phosphate).
• Atrophy, CRF (due to pressure atrophy).
Outline cystic kidney disease.
• Kidney is pack of million nephrons.
- Lots of tubules - cystic kidneys common.
• Cysts form due to misconnection.
- Any misconnection, congenital or acquired leads to cysts.
- Commonest is polycystic kidney disease - adult type. Simple cysts also common but they don’t produce many clinical symptoms.
• Genetic/Acquired.
Genetic PKD:
• Adult Polycystic Kidney (ADPKD) - autosomal dominant.
• Infantile Polycystic Kidney (ARPKD) - autosomal recessive.
• Uraemic Medullary Cysts.
• Renal Dysplasia.
• Medullary sponge kidney.
Acquired PKD: • Simple cysts* - Usually no clinical significance. • Dialysis associated cysts. - Multiple cysts in chronic kidney/renal failure.
Outline Autosomal Dominant PKD/Adult/ADPKD
• Common, Autosomal Dominant ~40y.
- 1 in 700 people. Usually present around 40 with symptoms.
• Partial lack of tubular development.
- Kidneys function partially but gradually develop chronic renal failure.
• Bilateral, large, cystic kidneys.
- Almost size of football.
Clinical features:
• Flank pain, mass, haematuria and UTI.
- Recurrent UTIs.
• Minor trauma → haematuria*
- Most commonly patients present with haematuria following a minor trauma.
• CRF ~50y, common cause of dialysis.
• PKD-1 gene (polycystin) mutation 85%. PKD-2 in 15%, PKD 3 rare.
- Commonest mutation is PKD-1 gene (polycystin) on chromosome 16.
Other associations: • Liver, splenic, pancreatic cysts (30%). - Associated with cysts in other organs. • Cerebral Berry aneurysms (20%). • Diverticulosis coli.
