RAD 240 PathologyRadiological Sciences, Department of Health SciencesWeek of November 17, 2013Dr ShaiLecture 7

Pathology of the

Kidney & Urinary

Tract

overviewKidney structural abnormalitiesDiseases of the glomerulusSystemic diseasesDiseases of tubules, vessels, & interstitiumNeoplasmsPathologies of renal tract

Renal anatomy

Structural – congenital kidney disorders

1. AGENESIS of the kidneyUNILATERAL in 1/1000 birthsSolitary kidney undergoes hypertrophySusceptible to infectionsMales 2:1 females, left kidney usually absent

BILATERAL in 1/3000 births, part of Potter’s syndromeAbnormal face, urinary tract and nervous systemOligohydramnios* in pregnancy as kidneys not present to contribute amniotic fluid (absence of fetal urine)Not compatible with post natal life (DEATH)

CONGENITAL CON’TB. HYPOPLASIA

Kidneys fail to reach normal adult size (congenitally or from shrinkage), often a result of early life chronic infection

C. ECTOPIC KIDNEYS1 or 2 kidneys in abnormal position (usually pelvis)

D. HORSESHOE KIDNEYPoles of kidneys are fused, usually inferiorly, to form a large U-shaped (horseshoe) kidney1/500 people, asymptomatic as collecting systems are normal2 to 8 times more likely to develop Wilm’s tumours in children

Horseshoe kidneys

Animated view CT abdomen – horseshoe kidney

Pathology specimen – horseshoe kidney

Ultra sound horseshoe kidney

Cystic Kidney DiseasesIncludes: Hereditary, developmental and acquired disordersImportant:

1. appropriate patient management to delay onset of renal failure2. Appropriate genetic counseling to relatives at risk

Adult Polycystic Kidney Disease (APKD)

Hereditary (Autosomal Dominant, 50% are new mutations)

Linked to alpha globin cluster on chromosome 16 Both kidneys replaced by cysts, develop over yearsIncidence: 1/250 live birthsAssociated with berry aneurysms (cerebral), liver cysts, pancreas, lung

In stillborns* or neonates with enlarged kidneys (15 times normal size) with radiating cystic pattern (SUNBURST PATTERN)Prognosis*: usually die within 2 months of life

Cystic disease of renal medulla

Medullary sponge kidney (tubular ectasia)Multiple cysts develop in renal papillaeIncidence: 1/20,000Renal function not impaired, but calculi (renal stones) develop and predispose* individual to renal colic & infection

CT - KIDNEY

GLOMERULUS ANATOMY & HISTOLOGY

Glomerular DiseasesTypically caused by structural abnormalities4 significant components may be damaged:

i) endothelial cells lining the capillaryIi) glomerular basement membrane (BM)Iii) mesangium: supporting mesentery to the capillary comprised of mesangial cells (phagocytic cells) & associated matricEpithelial cells or podoctyes, coat outer layer of BM

Patterns of glomerular disease

Most diseases affect different glomeruli to varying degreesGlobal: affecting entire glomerulus uniformlySegmental: affecting one glomerular segment, sparing othersDiffuse: affecting all glomeruli in both kidneysFocal: affecting proportion of glomeruli, sparing othersEg. “diffuse global” or “ focal segmental”

Aetiology of glomerular diseases

Primary (majority): disease begins in glomerululusTypes: proliferative*, membrnaous, glomerulosclerotic, minimal change lesions

Secondary: 2nd ary to systemic disease (immune complex mediated, metabolic, vascular)

Hereditary: Alport’s Syndrome, Fabry’s disease, congenital nephortic syndrome

Diagnosis & SymptomsHistologically

Glomerular response to injuryPercutaneous* needle biopsyImmunological comple deposition investigation

Symptoms• Aymptomatic haematuria*

• Haematuria without proteinaemia, continuous or intermittent, does not cause renal failure

• Aymptomatic proteinuria*• Proteinuria >0.3 g / 24 hours, without haematuria,

continuous, orthostatic (postural), or transient• Acute Nephritic syndrome

• Sudden haematuria, proteinuria, hypertension• Loin pain, headache, orbital oedema*

• Nephrotic syndrome• Proteinuria >3.5 g / 24 hrs, with hypoproteinaemia,

oedema, hypercholesterolaemia

• Chronic Renal failure• Irreversible deterioration in renal function caused by

the destruction of nephrons over time• Impairment of excretory, metabolic, endocrine functions

of kidney• Management: excretory function may be replaced by

dialysis, metabolic and endcrine functions need transplant to re initiate

Proliferative glomerulonephritis

Group of disorders characterized by histological degrees of proliferation in mesangial & epithelial cells in glomerulusTypes

Diffuse proliferativeRapidly progressiveFocal proliferativeMembranoproliferative* these are patterns of reactions, not diagnoses

Diffuse proliferative glomerulonephropathie

sDiffuse, global, acute inflammation

From deposition of immune complexes in glomeruliStimulated by infectionAetiology: post streptococcal infection , or less frequently viruses, protozoas and other bacterial infection

Rapdily progressive glomerulonephritis

CRESCENTIC GLOMERULONEPHRITIS (RPGN)

From severe glomerular injury characterized by formation of cellular crescent shaped masses within Bowman’s spaceOften post streptococcalCrescent shaped masses are composed of epithelial cells & macrophages, causing glomerular ischaemia

Focal proliferative glomerulonephritis

Acute inflammation within cellular proliferation in a few glomeruli (focal), affecting one segment (segmental)Better known as focal segmental proliferative glomerulonephritis

Primary: mesangial IgA disease, Goodpasteur’s syndromeSecondary: systemic endocarditis, vasculitis, connective tissue disease

Membranoproliferative glomerulonephritis

MPGN

Diffuse, global pattern of glomerulonephritis with thickening of membranePrimary: idiopathicSecondary: associated with SLE, endocarditis, cerebral shunts

Minimal change diseaseLIPOID NEPHROSIS

No significant abnormality can be detected by light microscopy*Children, under age 6 years, males more than femalesAetiology: unknownPathogenesis: thought to be immunologicalMorphological features: on electron microscopy* diagnostic loss of epithelial foot processes, tubules show accumulation of lipid in cellsPrognosis: good, no permanent renal damage

Minimal change disease – electron microscopy

Hereditary glomerulonephritis1. Alport’s Syndrome

Clinical triad: deafness, glomerulonephritis, ocular lesionsX linked inherited*, mutatin of COLIValpha5 geneClinical features: glomerulonephritis (microscopic haematuria & proteinuria in childhood, later nephrotic syndrome), ocular disease & deafness to high pitched sounds

2. Fabry’s syndromeRare, X linked recessive syndromeGlycosphingolipid metabolism, resulting in painful extermities, red hyperkeratotic papules on skin*, proteinura, renal failure

Congenital Nephrotic Syndrome: rare, mesangial proliferation or glomerulosclerosis

Chronic GlomerulonephritisChronic renal failure with small contracted kidneys,

and all glomeruli are hyalinized (end stage kidneys)Macroscopically: affected kidneys are small, granularity of external surface, scarring from nephron hyalinizationMicroscopically: hyalinization of glomeruli

Systemic diseasesSystemic lupus erythematosus

Renal involvement causes diffuse or focal glomerular disease Basis of glomerular damage is immune complex deposition in basement membrane, BM thickens

Henoch Schonlein purpuraImmune complex mediated systemic vasculitisAffects small arteries in skin, joints, gut, kidneys

Bacterial EndocarditisRenal lesions in infective endocarditis from immune complexes or embolism infarction of heart valve vegetations

Diabetic GlomerulosclerosisDiabetic glomerular damage causes increased permeability of capillaries in the BM, leading to proteinuris and nephrotic syndromePathogenesis: not fully understood, involves deficiency in proteoglycans, glomerular hypertrophy, BM thickening, mesangial cell hypertrophyHistologically

1) capillary wall thickening – mild proteinuria2) diffuse glomerulosclerosis3) nodular glomerulosclerosis

AmyloidosisAmyloid, an extra cellular fibrillar protein* is deposited in tissues, including kidneyAmyloid fibrils deposited in BM, and mesangiumProteinuria & nephrotic syndrome & chronic renal failure

Wegener’s GranulomatosisImmune complex, systemic, necrotizing vasculitis, affecting nose, respiratory and renal tracts

Polyarteritis nodosaSystemic disease, inflammatory necrosis of walls of small & mediums sized arteriesNecrosis of medium sized arteries causes infarcts in the kidney, as fibrinoid necrosis

Vascular DiseasesBenign Nephrosclerosis

Hyaline arteriosclerosis of the kidney, associated with benign hypertension*It is an important complication of long term benign hypertension, chronic renal failure being the most important outcomeIt is the commonest nephropathy, found in about 75% of autopsies over the age of 60 years

Long standing hypertension cuases reduced blood flow to glomeruli, caused by vascular changes, branches of renal artery thicken with hypertrophy of muscular media, results in ischaemia with scarring.Afferent arterioloes undergo hyalinization (arteriosclerosis)

Clinically: increase blood urea & reduction in creatinine clearancePrognosis: <5% die from renal failure, death from congestive heart failure associated with renal failure

nephrosclerosis

Malignant nephrosclerosis

Renal disease associated with malignant hypertension

Pathogenesis: in accelerated hypertension, the rise in blood pressure is rapid, large muscular vessels undergo fibroplastic proliferation, BUT NO MUSCULAR HYPERTROPHY

Afferent arterioles undergo necrosis, and necrosis of glomerular capillary network.90% of cases untreated cause death.

Renal artery stenosis

Narrowing of renal arteries, from atherosclerosis or arterial fibromuscular dysplasiaOutcomes

Chronic ischaemia of affected kidneyRenovascular hypertension

Inadequate perfusion of kidney caused by renal artery stenosis leads to hypertension, and abnormal activation of the renin-angiotensin system

Neoplasms of the kidney

Benign tumoursCortical adenoma: epithelial tumours of renal tubular epitheliumMacroscopically: discreet nodules < 20mm diameter in cortex Microscopically: well differentiated large clear cells

Renal hamartoma: commonest benign tumour of kidney, made of spindle cellsMacroscopically: firm white nodules in medulla, 3-10mm sizeMicroscopically: spindle cells

Angiomyolipoma: hamartoma* composed of smooth muscle, blood vessels, and fate.

Renal hamartoma

Malignant tumours of kidneyRenal cell carcinoma

Adenocarcinoma made of renal tubular epithelium, in adults3% of all carcinomas, 90% of primary malignant renal tumoursMales 3:1 femalesAssociated with tobacco use, and patients with von Hippel Linday syndrome, paraneoplastic syndomes (hypercalcaemia, hypertension, polycythaemia)*Macroscopically: tumours in upper pole of kidney, rounded masses, yellow surface with areas of haemorrhage & necrosisMicroscopically: clear of granular cell types (referring to cytoplasm of cells)Symptoms: haematuria, loin pain, loin massPrognosis: 70% chance 10 year survival

Renal cell carcinoma imaging

Wilm’s TumourNephroblastoma

Malignant embryonal tumour derived from primitive metanephros*Common in childhood, peak 1 to 4 yrs age3 types identified

Commonest : tumour suppresor gene WT1 located on chromosome 11

Macroscopically: large rounded masses of solid, fleshy white lesions with necrosis. Tumour is aggressive, rapidly growing, extends beyond capsules into mesenteryMicroscopically: composed of up to 4 elements {primitive blastematous tissue, immature glomerular structures, epithelial tubes, stroma of spindle cells)Presents with abdominal mass, treat with chemo and radio therapy

Wilm’s tumour

Macroscopical changes in Wilms tumour and CT imaging of Wilm’s tumour

Urinary tract obstructionObstruction of urine drainage from kidney at ANY level

within urinary tractIntrinsic lesions: within ureteric wall or lumen (eg urinary calculus*, necrotic debris*, fibrosis after trauma or infection)Extrinsic lesions: from external pressue (eg tumours of rectum or bladder, pregnancy, retroperitoneal fibrosis)

LocationsRenal pelvis: calculi, tumoursPelviureteric junction: strictures, calculi, ext compressionUreter: calculi, ext compression (pregnancy, fibrosis, tumour)Bladder neck: tumour, calculiUrethra: porstatic hyperplasia or carcinoma, stricture

Pathogenesis: obstruction at any point causes increased presure, superior to blockage, with dilatation of renal pelvis and calyces (hydronephrosis)

Obstruction ate pelviureteric junction > hydronephrosis@ ureter> hydro ureter with subsequent hydronephrosis@ bladder neck> bladder distension with hypertrophy of bladder muscle > hydroureter and hydronephrosis

Hydronephrosis effects:Fluid entering the collecting ducts cannot empty into renal pelvis, and intra renal resorption of fluid occursIf the obstruction is removed at this stage: normal renal function resumes

Urolithiasis (urinary calculi)Formation of stones in the urinary tract (U/S)

1-5% population in UK, usually after 30 years age, males> femalesCan form anywhere in urinary tract, usually in renal pelvis

Composition of stonesCalcium oxalate (80%)Triple phosphates (15%) magnesium ammonium phosphate stonesUric acid (5%)Calculi in cystinuria and oxalosis

Aetiology: acquired (urinary tract obstruction, persistent urinary tract infections, reduced urine volume from dehydration; or inherited 1ary metabolic disorders, cystinuria, etc

Mechanism of stone formation involves excess solute in urine (primary increase in metabolite or stasis) or due to reduced solubility of solute in urine (persistently low pH)

Calculi vary in size, from sand like particles to large staghorn stones which fit the whole renal pelvis and branch into calycesIf calcium deposition occurs, nephrocalcinosisSymptoms:

Renal colic* with nausesa & vomitting caused by passage of small stones along ureterDull ache in loins Strangury* desire to pass something that will not pass (stones in bladder)Recurrent urinary tract infections (UTI)Management: rest, analgesia, warmth, fluid intake to pass small stones <5mm, or ureteroscopy or lithotripsy

Urinary calculi imaging

CYSTITISInflammation of bladder

Extremely common, mostly women because of shorter urethra (less traveling distance for bacteria)Aetiology

Infection or irritants (radiation)Bacterial (E Coli, proteus, strep faecalis, staphylococcus)Viral (adenovirus), fungal (candida), parasites (schistosoma)

Macroscopically: acute inflammation with oedema, erythema & ulceration of bladder mucosaMicroscopically: infiltration of mucosa with acute inflammatory cells

Risk factors:Urinary retention (due to obstruction, bladder paralysis, calculi, foreign bodies/diverticuli, uterine prolapse)Infection of adjacent structures (prastatitis, urethritis, colon disease)Diabetes mellitusPregnancyTrauama (catherization)

Routes of infectionAscending (commonest) urethra then bladder infection (catheterization)Descending from kidney (eg renal tuberculosis)Direct spread or hameatogenous, or lymphatic

Clinical features: pyrexia*, pain in rt iliac fossa*, loin and supra pubic pain, micturition disorders (frequency, urgency, dysuria*, haematuria, incontinence*)

Examination: mid stream urine analysisTreatment: anit bacterial, antibiotics, flluid therapySequelae:

ResolutionChronicityPyelonephritis*

Bladder metaplasiaGLANDULAR METAPLASIA (CYSTITIS GLANDULARIS)

Small, rounded urothelial cells under urothelial surface (Brunn’s nests)Develop central lumen surrounded by cuboidal cells

ADENOMATOUS METAPLASIABenign, metaplsia or urothelium to cuboidal epithelium

SQUAMOUS METAPLASIAKeratinizing or non keratinizing

BLADDER TUMOURSTRANSITIONAL CELL CARCINOMA

Incidence: 1/5000 in UK, 3% of all cancer deathsMales 3: 1 females, 60-70 years

AetiologyChemical: eposure to environmental agents (cigarette smoking, aniline dyes, rubber industry)Leucoplakia: keratinizing metaplsia, white plaques and calculiBladder diverticuli*

Most occur at base of trigone*

Transitional cell CT and histology

MORPHOLOGYPapillary (commonest) warty masses, projecting into lumen with little invasion of bladder wallSolid: tumours grow directly into bladder wall, often ulceratedMixed papillary and solidFlat in situ carcinoma: reddened mucosa

GRADINGTCC grades I-IIII: well differentiated, no invasionII: moderately well differentiated, papillary ,atypical cellsIII: poorly differentaited, pleomorphic* cells, invasive

Bladder cancer staging

TNM Tumour-node-metastasis Staging

T1: tumour confined to mucosa or submucosaT2: superficial muscle involvedT3: deep muscle involvedT4: invasion beyond the bladder

Spread: local to pelvic structures, lymph or haematogenousTreatment: stage dependeant, diathermy +- radiotheapy, cystectomy or palliative* radiotherapyPrognosis: depends on histoogical type

Try…Search online and app based radiology slides and identify both normal and abnormal structures

2ND MID TERM EXAMINATION:COVER CARDIOVASCULAR, RESPIRATORY, URINARY, GASTROINTESTINAL PATHOLGIESMULTIPLE CHOICE AND SHORT ANSWERS

REVIEW CLASS BEFORE THE EXAM: please start studying, so you can optimize the review time, good luck’