Morphology Lecture

Pathology of the kidney and urinary tract - Course

Course content RENAL DISEASES Glomerular nephropathies - GN 2. Tubulo-interstitial nephropathies (NTl) 3. Vascular NPs-vascular kidney damages in HTA 4. Renal Tumors 1.

DISEASES OF LOWER URINARY TRACT 1. Infections of lower urinary tract 2. Obstructive Uropathy (hidronephrosis) 3. Renal lithiasis (Urolitiasis) 4.Tumors of LUT 5. Malformations of the kidney and urinary tract

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Nephropathies (NP) NP=bilateral renal diseases with varied clinical picture and morphological substrate depending on the location of primarY lesions - 3 categories of NPs: - glomerular - tubular - interstitial

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Main functional unit of the kidney =nephron

GLOMERULAR NPS renal diseases that have in common the location of the primarY lesion at the level of glomerulus

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Diagnosis (biopsyPBR):

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optical microscopy (Mo) PAS-show memDranes

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0rawrng gromerurar and tubular basal membranes

immunofluorescenc

e (lF) releaves locafion of antigens, complement and

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Glomerular NPs After degree of glomerular damage ) 4 types of glomerular diseases: (a) global: entire glomerulus is affected; (b) segmental: glomerulus is partially affected (1-2 segments); (c) diffuse: all glomeruli are affected; (d) focal: only some glomeruli are affected.

Clinical picture of glomerular NPs clinical picture

renal disease

Nephritic syndrome

Nephrotic syndrome

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Sn

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SN

Hematuria, Oliguria, Azotemia, Hypertension Massive proteinuria, Hypoalbuminemia, Edema,

Hyperlipidemial-uria Mixt syndrome

Association of Sn and SN

Acute renal failure: oliguria

uremta (weeks/months)

Chronic renal failure: prolonged

uremia (years)

uremia

Glomerular NPs Clinicall!

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+ 2main tYPes:

primary GNPs or glomerulonephfritis --- initial involvement of glomerulus systemic (secondarY) GNPs or glomerulonephfritis - systemic diseases affecting secondary glomeruli

Glomerular diseases Primary GD

syndrome - Nephrotic . Minimal change disease .

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Nephritic

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Membranous nephropathy or

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glomerulonephritis-GN Crescentic GN

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Primary hematuria

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Membranoproliferative

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glomeruloneph ritis-G lgA nephropathy

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Glomerular NPs with nephritic syndrome

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diffuse proliferative glomerulonefritis

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rapidly progressive glomerulonefritis (with crescents)

Diffuse proliferative glomerulonefritis immune complication wlth diffuse involvement of olomeruli that occurs at 2-4 weeks afier an infection with B haemolytic streptococcus group A any age, most frequently in children (6-10 years) is manifested with Sn

oranular deposits of immune Eomplexes in the capillary walls

larqe electron-dense nodular deFosits of immune complexes disoosed on the external surface of GBM

Diffuse proliferative glomerulonefritis MO

. diffuse olomerular lesion: all qlomeruli are affeited simultaneously, 6ilaterally . qlomerulus is increased in volumehipercellularity . endothelial and mesangial cell oroliferation . influx of neutrophils in capillary lumen, with obliteraration of capillary lumen . renal tubules are normal ME . nodular deposits of immune comolexes arranqed - on the external surfdce of GBM Evolution (95%) completely healing at children (5o/o). recovery is reduced at adults -

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RPG

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RPG-Rapidly prog ressive glomerulonefritis (epithel ial crescents) RPG = rapid and progressive loss of renal function in several months and death by CRF different etiology and pathogenic mechanisms

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proliferation of parietal epithelial cells of Bowman with capsule obstruction of Bowman space and compressing of the glomerular capillaries

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Primary glomerular NPs with nephrotic syndrome

. Minimal change disease (llpoid nephrosis) . Membranous nephropathy

Minimal change disease (lipoid nephrosis) .

the most common cause of

nephrotic syndrome in children (1-

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etiology

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primary or idiopatic: cause is not

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orimarv lesion is qlomerular tusion bf e>,tracap-i lary epithel ial cell orocesses . eoithelial cells come into direct contact with the GBM, which becomes permeable with loss of lipoproteins, which are reabsorbed at the level of renaltubules IMF does not show the presence of complement or lgs

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Minimal change disease (lipoid nephrosis) MO

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glomeruli are normal oroximal tubular epithelial cells bre loaded with lipids ) old term of lipoid nephrosis reflects the oresence of numerous fat droos into renal tubules

MA . kidnevs are increased of volunie, the renal cortex being pale-yellow (by accumulation of lioids in the tubular epithelium) and with smooth external surface . Evolution:

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good in children unfavorable in adults

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the most common cause of nephrotic syndrome in adults Etiology . primary or idiopathic (80-90%) . secondary to systemic diseases (10-20%) EM

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early, immune complex deposits on the external surface of GBM with GBM expansion between these deposits looking as radiary spikes (aspect of wheel) late, the spikes fuse and include immune deposits resulting a lacy appearance

M.E. - thickened GBI\4 by deposition of immune cx Ag-Ac on the extemal epithelial surface of MB

Mem branous G lomeru loneph ritis .MO

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(a) early-normal appearance of glomerular capillary walls; (b) late-diffuse thickeni ng of GBM.

lmmunofluorescence granular deposits of lg G and complement on the external surface of GBM MO - metenamin - silver stain: deposition of new matrix of GBM around immune complexes

Glomerular NP with mixt sYndrome (nephritic Ai nephrotic syndromes)

memb ranoproliferative G N - is manifested with mixt syndrome (Sn and SN) - etiology

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primary or idioPathic secondary to some systemic diseases: LES and lE

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Type

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mesangial cell. proliferation with mesanglum Interposlng between the external and internal laver of GBM (appeararice of double contour)

Type ll

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marked thickening of GBM bY immune dePosits tnto GBM (immune complex dePosit disease)

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type

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mesanqial cell proliferation and increasbd mesangial matrix (Sn) lobular appearance ot

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glomerulus type ll thickening of GBM (SN)

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Secondary glomerular diseases and complications Secondary glomerular disease

- Diabetic glomerulosclerosis-GS - Renal amyloidosis Complications . Chronic glomerulonephritis-GNC

Diabetic nePhroPathY - ls manifested as:

. .

.

diabetic diffuse (Bell) or nodular (Kimmelstiel-Wilson) glomerulosclerosis papillary renal necrosis- papillary vessel thrombosis with removing ureter obstruction and ARF of papillary necrotic area into ureter '' acute suppurative pielonephritis-predisposition to bacterial interstitial infections

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Diabetic glomeru losclerosis manifestation of diabetic m

icroangioPathY: reti noPathY,

ischemic heart dtsease ano peripheral vascular insuffi ciency MO-3 types of glomerular lesions

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GBM thickening is the most earlY form of diabetiC microangioPathY = PAS (+) deposits diffuse GS (Sdr. Bell) consists of diffuse dePosits of PAS (+) material into glomerular mesanglum

nodular GS (Kimmelstiel-Wilson sdr) consists of nodular dePosits of PAS (+) material into glomerular mesangium

Evolution-deposits i ncrease with obliteration cif capillary lumen and development of CRF

Amyloid nePhropathY renal amyloidosis

- is a target organ in systemic reactive amYloidosis Clinically - nePhrotic sYndrome Kidney

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kidneys are normal or slightlY increased in size, looking as translucent, waxY structure having elastic, rubberry consistencY

Ml - amyloid dePosits occur on mesangium and GBM

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blood vessels

tubular BM ln advanced disease occurs entire obliteration of glomeruli )CRF

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Chronic g lomerulonePhritis end siage of renal disease

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end stage of glomerular-nelropathies . and is the main cause ol chronlc renal failure Morphology MA

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both kidneys are atrophied, pales with an adherent capsule and fine granular external surface On the cut section, the cortex is atrophied with hilar adipose tisuue hyperplasia

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Glomeruli are hvalinized and corresponding tirbules are replaced by connective tissue A reduced number of glomeruli and tubules are hypertrophied, (increased in volum but i/ith a riormal function) giving the appearance of cortical

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microgranulararity There is a marked interstitial fibrosis associated with chronic inflammation

Small kidney with microgranular external surface

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lar-interstitial neph ropathies

lmpairement of renal tubules and interstitium represents an imporlant cause of renal failure NTI Classification: (1) acute tubular necrosis (2) tubulo interstitial nephritis (3) pielonephritis

Acute tubular necrosis -NTA .

Morphology

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tubular epithelial necrosis

renalfailure (lRA)

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is manifested clinically by acute

etiology - 2 main groups

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lschemic Toxic

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hypovolemic shock or acute bleeding severe burns

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Endogenous: myoglobinuria exogenous: heavy metals (Pb, Hg), organic solvents (CHC|3' CCl4), drugs (Ab, NSAIDS)

ischemic tubular necrosis - insufficient kidney perfusion caused by

toxic tubular necrosis - nephrotoxic substances:

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Acute tubular necrosis -NTA MA

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kidneys are enlarg.ed,, pale,.friable (appearance ot Dolleo meal); on cut section - the renal cortex is pale, and medulla is congested.

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toxic acute tubulonecrosis the lesions are located in proximal epithelial tubules )tubular epithelial necrosls

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necrotic epithelial cells have uniform appearance, acidoPhilic, without nuclei, some are detached and fall in the lumen (epithelial cylinders or casts). tubular BM is intact, forming the support for ePithelial remaining cell regeneration normal glomeruli

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nterstitial neph ritis . .

deqenerative tubular lesions and int6rstitial inflammatory infiltrate acute and chronic tubulo-interstitial nephritis (NTIA) . 2-3 weeks after exPosure to a causative agent - cirugs ) allergic manifestations

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edema and interstitial inflam matory infiltrate with lymphocytes and eosinoPhils degenerative tubular lesions (focal tubular necrosis)

Evolution

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reversible - stoPPing drug administration rapidly progressive renal failure

Drug-induced interstitial nephritis

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Pyelonephritis

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Urinary catheter colonized by E coli or Proteus

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Macroscopy ascending PNA - SS

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Hvperaemic pielocaliceal mucosa is'covered bY a Purulent exudate Suppurative medularY lines radiatin g toward cortex Cortical large abscesses, Yellow, irregular, surrounded bY an area of hyperaemia; laroe areas of suPpuration coifluenting with'wedge shaPe

descending PNA (PYoemic abscesses)

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affected kidneYs are swelled and conqested and Presents dissbminated microabscesses on the external renal surfaces. microabscesses aPPear as Yellow nodules, 2 mm in diameter, under tension, surrounded bY an hyperaemlc area.

Acute pyelonephritis with abscesses

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Microscopy MI

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interstitial microabscesses containing occasional microbial colonies tubular damage PMNs form leucocitarY casts or cylinders in renal tubules glomeruli are normal

Evolution: (a) favorable: healing by connective

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' organization (cortical fibrosis

leaves deep scars); (b) unfavorable: renal papillary necrosis in diabetics

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perinephriticabscess PNC - recurrent infections septicemia with BGN and shock

Chronic pyelonePh ritis Cronic renal disease, that occurs after repeated renal infections followed by healing Clinically, disease is manifested through HTA and cRF Diagnosis

- affected kidneys are contracted asymmetrically - deformation of pielocaliceal system Etiology infection) specific patogens: Mycobacterium tuberculosis

- indistinctive patogens (non-specific -

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Unspecific chronic pyelonephritis Macroscopv:

-

rerial oelvis is dilated and deformed with thickened mucosa kidnev - is diminished and asvminetric (deep scars in the foim of wedge, with iregular, decreased cortex and atrophled medulla).

Microscopy chronic inflammation and interstitial fibrosis in the renal papillary atroPhY and pelvis fibrosis dilated tubules, bounded bY an atrophied epithelium, contain a prot'einaceous, eosi noPhilic inaterial giving. a histologic thyroid apperance ot me Kloney qlomeruliare hvalinized (HTA) 5nd vessel walls are marked thickened

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Specific chron ic pyelonePhritis (tuberculous PNC) Etiology-mycobacterium Pathogeny

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tuberculos is

blood dissemination from a primary pulmonary localization ascending infection from genital foci

Diagnosis

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morphology - evidence of tuberculous oranuloma iricrobiotogy - evidence of mycobacterium tuberculosis in the urine

Macroscopy-2 forms:

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Nodular: multiple cazeous nodules of 0,5-2 cm in diameter Ulcerative: destructive renal parenchyma through caseous materlal removed by urine

Complications:

-

ln the unilateral lesion the extension of

inflammation reaches the bladder with secondary affectton of the other kidney Bilateral lesions progress to the chronic renal failure and death

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RENAL TUMORS

. Primary Tumors - Benign Tumors .

.

Adenoma Fibroma

- Malignant . .

Tumors

Renal clear cell carcinoma Nephroblastoma

. Secondary

tumors (rare)

Benign tumors - are without clinical significance at postmortem examination

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in 20% - incidental aspects

hrtrallgnant tumons

. Primary - Renal adenocarcinoma (Grawitz T) - Nephroblatoma ( Wilms T)

. Secondary - multiple nodules - rare

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Renal clear cell carcinoma or renal adenocarcinoma (G rawitz Tl

the most common malignant kidney tumor in adults (50 - 60 years old) 90o/o of malignant kidney tumors most frequent in men (2 | 1) origin-renal tubular epithelium (proximal and distal contort tubules) clinically-hematuria, lumbar pain and abdominal tumor mass

Macroscopy SE-polar tumoral masses with false encapsulation, proiemining from the kidney cortex SS- characteristic appearance, yellow-g ray, with areas of necrosis and hemorrhage

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hill-ranal adenocarcinor-n& Tumoral architecture: various types of growth

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Tubular-adenocarcinoma Papillary Solid

Cytology

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tumoral parenchyma-clear polygonal cells with distinct cell membranes, central and hypercromatic nuclei and clear cytoplasm containing glycogen or fat delicate stroma very well vascularized

-

Renal clear cell carcinoma - CCR Dissemination

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hematogenous way (cords of tumor cells are present in the renal vein and inferior vena cava) lymphatic pathway direct way (to the renal Pelvis)

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Unfavorable prognosis - aggressive tumor has a tendency to be silent until it reaches large dimensions, often being metastatic at diagnosis.

The most affected organs are lung, brain, bones, liver, adrenal, lymph nodes and controlateral kidney. Prognosis - Reserved - RS at 10 Years is 20% Treatment

-

surgical resection of the tumor

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Nephroblastoma (Wilms T) .

. . .

the most common malignant tumor in childhood i*ith mlximum frequeri'cy between 1- 4 years) equal incidence at both sexes embryonic tumor derived from remaining nefroblastema in the renal Pelvis mixed neoplasm compg.sqd of metane.phric blastema dnd its epithelial and stromal Oerivitives in varyi'ng stages of differentiation clinical Picture -abdominaltumoralmass,observedin90%ofcases

- hematuria, HTA

MacroscoPY tumor clearlY defined and encaPsulated

.SS - white-graY, lobular with areas -

appearance, of necrosis and hemorrhage tumor is bounded bY a rim of normal renal parencnyma renal Pelvis is comPressed

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Microscopy =>the tumor has a triphasic structure - epithelial component (immature glomerular and tubular structures) stromal component looking as sarcomatous tumor primitive blastema composed of small cells (metanephric blastema)

-

-

Dissemination and prognosis Dissemination

-

lymphatic pathway in hilar, and para-aortic lymph nodes hematogenous way - in the lung, liver, adrenal, diaphragm, retroperitoneum and bones

Prognosis - microscopic appearance:

-

marked glomerular and tubular differentiation is associated with a good prognosis nuclear pleomorphism and presence of abnormal mitotic figures are associated with a worse prognosis

The treatment consists of surgical resection and systemic chemotherapy, associated with radiotherapy of the affected area

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Diseases of lower urinary tract - LUT 1. Infections of lower urinary tract 2. Obstructive uropathy (hidronephrosis) 3. Renal lithiasis (Urolithiasis) 4.Tumors of lower urinarY tract 5. Malformations of the kidney and urinary tract

1. Infections of lower urinary tract

. . .

are favored by obstruction of LUT and secondary urinary stasis; are caused by BGN of the the colon: E.coli, Proteus, etc. LUT infections are presenting different names after location:

-

pelvic mucosa (Pielitis) ureteral mucosa (uretheritis) bladder mucosa (cYstitis) urethral mucosa (urethritis)

Cystitis . . . .

inflammation of the bladder mucosa of bacterial cause types. acute and chronic Acute exudative cystitis: differenttypes dependi!9 o.n the type of inflammatory exudate: catharal, haemorrnagtc' suppuratlve Chronic non-sPecific cYstitis infections of UTI - recurrentinflammation and fibrosis in the bladder wall

- chronic . Chronic specific cystitis (tuberculosis) -

secondary to a tbc PNC or genital tuberculosis Macroscopy: ulcerative lessions of the mucosa Microscopy: the caseous granuloma (tuberculous granuloma)

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2. Renal lithiasis (Urolithiasis) renal disease characterized by abnormal precipitation of urinary salts with formation of solitary or multiple, uni or bilateral calculi (calcium oxalate, calcium phosphate, etc ) Causes: (a) the increased concentration of urinary salts (dehydration, stasis); (b) low solubility of salts in the urine due to a changed pH (renal diseases, metabolic diseases)

Renal lithiasis Locations (2)

-

pielo - caliceal system

. .

-

small and multiple calculi through mobilization produce lumbar oain laroe calculi cause ob5truction and urinary stasis (hidronephrosis and iecondary infections)

bladder

. .

calculi coming from ureter local calculi secondary formed by urethral obstruction

Complications

-

persistent infections: PNC, ilyonephrosis, peri nephric abscess scuamous metaplasia and LJDU

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3. Obstructive uroPathY

(hydronephrosis)

.

Hydronephrosis = renal pelvis dilation caused by chronic obstruction of the urinary tract of different causes Causes:

- nodular prostate hyPerPlasia - calculi - malignant tumors (cervical or bladder carcinoma) Consequences:

- urinary dilatation tract -

atrophy by compression of the renal parenchyma (accumulation of urine above the obstacle).

Morphology Macrosco py (2 evolutive forms): - primary hydronePhrosis

.

.

-

moderate dilatation of the renal pelvis, with a slight

wallthinning normal renal ParenchYma (without kidneY damage)

secondary

hydronephrosis

.

.

massive dilatation of the renal pelvis, with very thin wall irreversible atroPhY and fibrosis of renal parenchyma Hidronefroza - Dilatarea sistemului pelvicalicial

26

4.Tumors of UT Origin: urothelial mucosal epithelium (transitional); Location: bladder and pielo-caliceal system; Types

a a

tumors: transitional papillomas - Benign . pediculated papillary tumor (2 cm);

Macroscopy: .Microscopy:connective-vascu|araxiscoveredbytransitiona| epithelium-with normal histology and cytology . Evolution: tendencY to reccure

tumors - Malignant .

Carcinomas-transitional carcinomas

Transitional . . . . .

Oriqin: urothelial mucosal epiihel i um (transitional)

-

Ma- vegetative tumor Microscopy.

atvpical transitional epithelium ) incieased number of cell laYers

Prognosis.- histological grade and stage ot olsease

-

.

smoking cigarettes mechanical irritation by calculi chronic infection

the most common location is the region of bladder trigon

.

;

favoring factors:

differentiated - good Prognosis undifferentiated - reserved prognosis

Treatment - lesion resection (local or total cYstectomY) followed bY irradiation.

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5.

Malformations of the kidneY and urinary tract

A Malformations of the kidney 1. Horseshoe kidney 2. Ectopic kidney 3. Policystic kidney

B. Malformations of urinarY tract 1. Double ureter uni or bilateral 2. Congenital stenosis of the urether

Malformations of the kidney 1. Horseshoe kidney the fusion by connective tissue of the 2 kidrievs at the level of inferior or sup'erior poles the ureters are located on the front aspect of the kidneYs the renalfunction is not affected 2. Ectopic kidnev = lack of ascdndinq kidnev to the renal lodge) t-he kidn'ey is located in the oelvis 3. Policystic kidney the presence of cysts in the kidney 2 types: adult and infantil tYPes

.

. .

. .

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Policystic kidney Adult type Autozomal dominant disease p- abnormal cell differentiation renal tubular ePithelial secondary hyperplasia tubular obstruction; the cystic changes develoP after birth. MA-enlarged and irregular kidneys (4 kg), comPosed of various sized cysts, (5-6 cm) containing a serous or bloodY fluid, separated from normal renal parenchYma

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.

Policystic kidneys Infantil type Autozomal recessive disease; P-lack of junction between nephron and collector tubule -> fusiforne ectasia of the collector channels; the cYstic changes are Present at birth. MA-kidneys are enlarged and have a preserved shaPe; theY are spongious on the cut surface due to the Presence of cystic fusiforme dilatation that extend radiary to the cortex and medulla.

. .

.

29

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b. Malformations of the urinary tract 1

. Uni or bilateral double ureter

-

the 2 ureters can fuse to a point above the bladder junction or they may have entire separate courses with different bladder entrances

2.Congenital stenosis of the ureter - the ureter lumen is congenital narrowed

30