Understanding Diseases of the Blood Vessels and Kidneys

1. Diseases involving blood vessels • Renal artery stenosis: - elderly (ARTS), younger patients fibromuscular hyperplasia (dysplasia) = hypertension Long term stenosis = atrophy • Kidney infarction: trombotic embolism (from heart), atheroma plaque material from aorta, trombosis (PAN) • Arteriosclerotic nefrosclerosis: ARTS aorta = branches ren. artery in parenchyma = „V“ shaped scars • Benign nefrosclerosis: benign hypertension Grossly: symmetrical atrophy, finely granulated surface Histology: hyalinne thickening of small arteries, arterioles = hyalinne arteriolosclerosis(insudation of plasma proteins into the wall = production of hyalinne matrix)

2. thickening = stenosis = ischemia = atrophy (collapse and obliteration G) = granulated surface, tubular atrophy, intersticial fibrosis Clinical course:: slight functional impairment, NO uremia • Malignant nefrosclerosis: malignant hypertension (TK 120) fibrinogen into the wall = endoth. injury = fibrinoid necrosis intimal hyperplasia = stenosis (ischemia) Ischemia (renin-ang.-aldos) = elev BP= mal. hypertension Grossly: petechial hemorrhages, granulated K, shrunken K Histol: - larger aa - concentric proliferation of intimal smooth m. cells (onion skin app.) = hyperplastic arteriolosclerosis - arterioles - fibrinoid necrosis (inflammation= arteriolitis) - glomeruli - segmental necrosis, crescents, obsolete G

3. Clinical course: - diastolic BP greater than 120 mm - papilledema (visual impairments) - encephalopathy (headaches, nausea, vomiting) - renal failure (inc. proteinuria, hematuria)

4. Systemic vasculitis • Polyarteritis nodosa: aa interlobulares, aa. arcuatae - fibrinoid necrosis, inflammation, trombosis = infarctions Glomeruli are not affected • Polyangiitis microscopica: interlobular arteries, affer. art., glomerular capilaries - necrosis, ANCA + Focal segmental necrotizing glomerulonephritis (crescents) • Wegener granulomatosis: morfology - see above periglomerular granulomas in addition, ANCA + • Alergic granulomatosis (Churg-Strauss syndrome) • focal segm. necrotizing glomerulonephritis + eosinophils

5. Renal stones • Urolithiasis: calculus in urinary coll. syst. (nephro-, ….) 75 % calcium oxalate (calcium phosphate) - hard, dark 15 % magnesium ammonium phosphate - white 10 % uric acid or cystine - round, smooth-surfaced, brown • Causes: often unclear, most important (calcium stones) --- 1. increased urineconcentrat. of the stone´s constituents = exceeding their solubility in urine (hypersaturation) (e.g.. idiopatic hypercalciuria, hypercalcemia...). 2. Persistent alkaline urine due to UTI (Proteus vulgaris) - magnesium ammonium phosphate stones 3. High uric acid level in urine (gout, cell break up...) or excretion of acid urine (pH under 5,5) - uric acid stones - defective renal transport of cystine - cystine stones

6. Renal stones • Supporting effects of stones formation:dehydratation,bacteriacolonies, epithelialdesquamation,calcification = nidi for stones formation • Morphology: - 80 % unilateral (r. pelves, calyces, bladder) - 20 % bilateral Number, shape and size varies (solitary x multiple), mm - cm, smooth, jagged, „staghorn“ • Clinical course: - large stones often asymptomatic or disordered outflow of urine - small stones into the ureter = hydronephrosis (dilation and infection), = renal/ureteral colic = hematuria

7. Hydronephrosis • Hydronephrosis = dilation of renal pelvis and calyces + atrophy of the renal parenchyma due to obstruction to the outflow of urine (obs. insidious x sudden, complete x incom) Obstruction at any level of the UT (renal pelvis - urethra) - obstruction below pelvis = hydroureter (dilation of the ureter) • C:Congenital - atresia of the uretra, - valve formations in either urethra or ureter, aberrant r.art. compressing ureter, renal ptosis with torsion or kinking of the ureter Acquired- „foreign bodies“ (stones, necrotic papila, blood coagulum), - tumors (prostate, bladder, ureter, uter.cervix, retroperit, rectum), - inflammation (prostate, retroperitoneal fibrosis, postinflammatory stricture of the ureter)

8. -neurogenic (bladder paralysis,), - pregnancy (mild, rev.) • Bilateral HN (obstruction below the level of the ureters) • Unilateral HN (obstruction at the ureter or above) Clinical c.: - sudden bilateral obstr = ARF without dilation - rapid unilateral obs = GF declined (in aff. K), fce normal - incomplete (intermitent) obs = dilation After obstruction GF persists some time = urine increases pressure in pelvis Grossly: long term obstr. = dilation of pelvis +(ureter), flat papilae, atrophied K parenchyma Micro: tubular dilation, interstitial edema, later atrophy of tubular epithelia, interstitial fibrosis, glomerulosclerosis HN incr. disposition to kidney infection = pyelonephritis !!!

9. Renal failure (uremia) • Azotemia:elevation of blood urea nitrogen and creatininelevels (related to decr. GFR, but not only…) - these metabolits either don not get into the kidneys (prerenal A) or Ks. can not clear them (renal, postrenal A) • Causes of A:prerenal(hypoperfusion - shock), renal (parenchymal disorders), postrenal (obstruction of the urine flow below the level of the kidneys) • When azotemia becomes associated with a constellation of clinical signs and symptoms and biochemical abnormalities = uremic syndrome (uremia)

10. Manifestations of the uremia - hyperkalemia (incr. kalium) = arytmia - fibrinous pericarditis - fibrinous pleuritis (incr. permeability of vessels) - gastroenteritis (hemorhagic gastritis, Treitz‘s pseudomembranous colitis) - lung edema (uremic lung = hyalinne membranes) - brain edema (uremic encephalopathy) = apatia, somnolence, convulsions - face edema (retention of Na+ and water) - peripheral neuropathy (disordered tendon reflexes) - anemia (hypoproduction of the erytropoetin)

11. - gray skin (anemia, deposition of the urine pigment) - renal tubules (deposition of the oxalate crystals) - renal osteopathy (damaged metabolism of the vitamin D, hyperphosphat, hypocalcemia = sec. hyperparathyreoidism = demineralisation and resorption of bone tissue - incr. disposition to bleeding (fragility of the capillaries) - metabolic acidosis (decreased excrecion of H+, decr. resorbtion of bicarbonate) - pancreatitis (uremic dehydratation and inspissation of secretion)

12. Tumors • BENIGNadenoma - in cortex, white nodules, solitary or multiple (acc. with nefroscler.), a few mm tubular, papilar angiomyolipoma - tuberous sclerosis (fat, vessels, sm. m.) oncocytoma - elderly p., centimeters, brown, centr. scar • MALIGNANT carcinoma (85% of mal. tumors of kidney) • clear cell carcinoma (70-80% of Ca kidney), 5.-7. decade, spheric, in cortex, a few cm, sometimes huge (> 10 cm) Grossly: yellow, hemorrhages, necrosis, cysts. Invasion of perirenal tissues, adrenal gl., pelvis and renal vein , vena c., right side of the heart („tumor trombus“)

13. Histology: from prox. tubules, clear cells (lipids, glykogen) Metastases: lung, brain, bone (patol. fracture), lymf nodes, thyroid gland, skin... Clinical course: symptoms vary (size, localization) - smaller tumors often incidentally (ultrasound, CT scan) - larger tumors: hematuria, flank pain, fever paraneoplastic syndrome: Cushing syndrome, polycytemia, hypercalcemia Metastasis is sometimes the first manifestation of tumor ! Prognosis: stage, nuclear grade, generally unfavourable • papillary ca (10-15%) (papilla formation, better prognosis) • chromophobe carcinoma (5%) favourable prognosis

14. Wilms tumor: children 2.- 4. year, from embryonal tissues Grossly: gray -white, necrosis, pseudocysts Histology: triphasic combination of nefrogenic blastema, epithelial structures and stromal str. (cartilage, muscle…) 5% foci of anaplasia (pleomorphic nuclei, atypical mitoses) Clinical course: pain, hematuria, palpable abdominal mass Very good prognosis ( 90 %), Anapl. tumors - meta (lung) • Renal pelvis carcinoma(urothelial) 5-10 % malignancies K Grossly: flat (usually invasive) or gray-white cauliflower -like (exofytic) - invasive/noninvasive (obstruction = HN) Histology: tumor papilli (papillocarcinoma) Clinical course: painless hematuria, meta to lymf nodes

15. Tumors of the ureter and urinary bladder Similar histological type like in pelvis (urothelial Ca) • Ureter = hematuria, obstruction (HN) • Bladder: 6.-7. decade, increased risk = exposure to beta-naphtylamine, smoking, chronic cystitis… • Grossly: flat or papillary(exophytic growth), later invasion into the wall of the bladder • Clinical course: hematuria, later obstruction of the ureters, metastases Prognosis depends on histologic grade and depth of invasion !!!