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Kidney and Male GU 2010.3

Kidney and Male GU 2010.3. Renal Vasculitis Prostatic carcinoma. Vasculitis. Inflammation and necrosis of blood vessels Capillaries -> Aorta. Examples of Vasculitis. Large blood vessels Giant cell (Temporal) Arteritis Medium sized vessels Polyarteritis Nodosa Small vessel vasculitis

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Kidney and Male GU 2010.3

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  1. Kidney and Male GU 2010.3 Renal Vasculitis Prostatic carcinoma

  2. Vasculitis • Inflammation and necrosis of blood vessels • Capillaries -> Aorta

  3. Examples of Vasculitis • Large blood vessels • Giant cell (Temporal) Arteritis • Medium sized vessels • Polyarteritis Nodosa • Small vessel vasculitis • Capillaries, venules, arterioles +/- small arteries • Systemic or one site only (skin, renal glomeruli)

  4. Vasculitis

  5. Vasculitis - artery in Polyarteritis Nodosa Inflammation of artery wall Lumen

  6. Glomerulus in vasculitis: crescents, necrosis • Crescent around glomerulus • Necrosis and small crescent Glom CRESCENT Nec Cres

  7. Typical of small vessel vasculitis in kidney Cr • Crescent: proliferation of cells inside Bowman’s capsule - blocks urinary space • Necrosis and crescent N Cr

  8. Vasculitis: Clinical, Serology • Acute renal failure, haematuria, proteinuria • Systemic signs: include rash, arthralgias, respiratory, neuromuscular symptoms • Duration of illness variable • ANCA (MPO, PR3) • (ANA, anti-GBM antibodies)

  9. Anti-neutrophil cytoplasmic antibodies (ANCA) • Serum antibodies to enzymes in neutrophil granules, monocyte lysosomes • Immunofluorescence: Cytoplasmic or Perinuclear • P-ANCA (anti-myeloperoxidase) in 80% of micro polyangiitis; more often indolent, renal limited • C-ANCA (anti-proteinase 3) in 90% of Wegener’s • Very useful in diagnosis; follow up of disease activity in Wegener’s with C-ANCA

  10. Crescentic GN, vasculitis: Immunofluorescence findings . .. ,. 65% “pauci-immune” • pauci = few or no IC • 20% immune complex • 15% anti-GBM

  11. Immunofluorescence, EM . .. ,. • Pauci-immune • (little / no immunofluorescent staining) • 90% of ANCA-assoc GN • Electron microscopy • GBM breaks, fibrin (indicate structural damage) • Crescent cells (epithelial > macrophages/lymphocytes) • No EM deposits

  12. ANCA-Mediated Glomerulonephritis • ANCA mediated, Pauci-immune Crescentic GN • Wegener’ granulomatosis • Microscopic polyangiitis • Churg-Strauss syndrome • Glomerular Pathology identical in all 3 • Pathology at other sites? Respiratory tract? • MPA may have different stage lesions, more chronic • ANCA Type PR3 or MPO • Specific diagnosis needs careful correlation • If prompt treatment: 75% 5year survival

  13. Chronic, partly healed lesions in vasculitis **Fibrocellular crescent Scar (healing) after necrosis Scar **

  14. Necrosis and/or Crescents in GN • PAUCI-IMMUNE (90% are ANCA-positive) • Microscopic polyangiitis, Wegener’s, Churg-Strauss, (drugs) • IMMUNE COMPLEX (also Electron dense deposits) • Henoch-Schlonlein purpura • Cryoglobulinemia • Lupus nephritis • Bacterial endocarditis • Drug reaction • other • ANTI-GBM DISEASE • Goodpasture’s syndrome and anti-GBM nephritis

  15. R D • 28 year old male • Acute renal failure • Pulmonary haemorrhage • N = Necrotic segment of glomerulus N

  16. R D Cres • Crescent, necrosis, fibrin • Linear staining for IgG • (EM: GBM breaks, fibrin)

  17. And Your Diagnosis is: ANCA-mediated? Immune complex? Anti-GBM disease?

  18. Prostate • Surrounds bladder neck and urethra • Normal weight = 20gm • Enlarged prostate palpable on rectal examination • CZ = Central zone • PZ = Peripheral zone

  19. Benign prostatic hyperplasia • Nodules around prostatic urethra • 70% men over 60 yrs • Growth requires dihydrotestosterone (Leydig cells), its metabolite 3-alpha-androstanediol & estrogens, which increase DHT receptor expression in prostatic tissue • DHT converted from testosterone by 5-alpha-reductase • BPH not precancerous • Clinical: • (None in most) • Obstruction - compression of urethra -> frequency, nocturia, etc • Dysuria because of UTI; acute retention

  20. Benign prostatic hyperplasia • Prostate = 40 - 200 gm • Nodules vary in size, colour and texture • Nodules consist of glands and / or fibromuscular stroma NODULE

  21. Benign prostatic hyperplasia • Treatment • None • Transurethral resection (TURP) • (Open prostatectomy for very enlarged prostates) • Medical treatment • 5 alpha-reductase inhibitor, or • Alpha adrenergic blockade

  22. Carcinoma of the prostate • Commonest cancer in males • Second leading cause of cancer deaths in men >50 • Incidence increases with age 70 >60 >50 yrs • Afro-Americans at earlier age >US whites >Asians • Endocrine, genetic & environmental factors • Androgens • Susceptibility loci on chromosomes 1 and 10 (near PTEN) • Incidence in Scandinavians > Japanese • Animal fat in diet? • Prostatic Intraepithelial Neoplasia (PIN) • in situ precursor of prostatic carcinoma

  23. Clinical presentation • Latent carcinoma - asymptomatic. Screening - PSA, PR +/- Transrectal Ultrasound, prostatic biopsies • PSA is a serine protease secreted by prostatic acinar cells, that liquifies the ejaculate. A single serum PSA test is not fully sensitive or specific. • Advanced carcinoma- obstruction or symptoms due to local extension or metastases e.g. bone pain.

  24. PSA in prostatic acini

  25. Preferential sites for prostatic lesions • Transverse section • BPH around prostatic urethra * • 70% of carcinomas are peripheral, and often posterior *

  26. Pathology • Peripheral in 70%, mostly posterior, palpable on PR • Often not easily recognised on gross examination • Invasion outside capsule; seminal vesicles, bladder • Lymphatics; bloodstream, osteoblastic mets late • Micro: Adenocarcinoma (different patterns = diff grades) • Grading: Gleason grade 1 ( virtually normal glands -> Gleason grade 5 (poorly differentiated). • Gleason score: add two predominant grades • Score = 6 predicts a good prognosis; 8-10 a poor prognosis • Immunostaining: PSA+, loss of HMW keratin staining

  27. Prostatic carcinoma - microscopic Gleason G 5 Gleason Grade 3

  28. Capsular & perineural invasion (L) and bone metastasis (R) Nerve

  29. Prostatic carcinoma stage, prognosis • Staging: clinical, PR, U/S, CT/MRI, bone scan, pathological stage in prostatectomy • T1, T2 - both treated by radical prostatectomy or radiotherapy • T3 locally invasive - radiotherapy • T4 metastatic - hormonal therapy • Prognosis: • Slow growing cancers • Stage and Gleason score • 90% 10 yr survival for T1, T2 • 10-40% for T4

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