RAD 240 PathologyRadiological Sciences, Department of Health Sciences

Week of November 17, 2013

Dr Shai

Lecture 7

Pathology of the

Kidney & Urinary

Tract

overview

Kidney structural abnormalities

Diseases of the glomerulus

Systemic diseases

Diseases of tubules, vessels, & interstitium

Neoplasms

Pathologies of renal tract

Renal anatomy

Structural – congenital kidney disorders

1. AGENESIS of the kidneyUNILATERAL in 1/1000 births

Solitary kidney undergoes hypertrophy

Susceptible to infections

Males 2:1 females, left kidney usually absent

BILATERAL in 1/3000 births, part of Potter’s syndrome

Abnormal face, urinary tract and nervous system

Oligohydramnios* 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) kidney

1/500 people, asymptomatic as collecting systems are normal

2 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 disorders

Important: 1. appropriate patient management to delay onset of renal failure

2. 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 years

Incidence: 1/250 live births

Associated 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 papillae

Incidence: 1/20,000

Renal function not impaired, but calculi (renal stones) develop and predispose* individual to renal colic & infection

CT - KIDNEY

GLOMERULUS ANATOMY & HISTOLOGY

Glomerular Diseases

Typically caused by structural abnormalities

4 significant components may be damaged:i) endothelial cells lining the capillary

Ii) glomerular basement membrane (BM)

Iii) mesangium: supporting mesentery to the capillary comprised of mesangial cells (phagocytic cells) & associated matric

Epithelial cells or podoctyes, coat outer layer of BM

Patterns of glomerular disease

Most diseases affect different glomeruli to varying degrees

Global: affecting entire glomerulus uniformly

Segmental: affecting one glomerular segment, sparing others

Diffuse: affecting all glomeruli in both kidneys

Focal: affecting proportion of glomeruli, sparing others

Eg. “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 injury

Percutaneous* needle biopsy

Immunological 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 glomerulus

TypesDiffuse proliferative

Rapidly progressive

Focal proliferative

Membranoproliferative

* these are patterns of reactions, not diagnoses

Diffuse proliferative glomerulonephropathie

sDiffuse, global, acute inflammation

From deposition of immune complexes in glomeruli

Stimulated by infection

Aetiology: 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 space

Often post streptococcal

Crescent 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 syndrome

Secondary: systemic endocarditis, vasculitis, connective tissue disease

Membranoproliferative glomerulonephritis

MPGN

Diffuse, global pattern of glomerulonephritis with thickening of membrane

Primary: idiopathic

Secondary: associated with SLE, endocarditis, cerebral shunts

Minimal change disease

LIPOID NEPHROSIS

No significant abnormality can be detected by light microscopy*

Children, under age 6 years, males more than females

Aetiology: unknown

Pathogenesis: thought to be immunological

Morphological features: on electron microscopy* diagnostic loss of epithelial foot processes, tubules show accumulation of lipid in cells

Prognosis: good, no permanent renal damage

Minimal change disease – electron microscopy

Hereditary glomerulonephritis

1. Alport’s SyndromeClinical triad: deafness, glomerulonephritis, ocular lesionsX linked inherited*, mutatin of COLIValpha5 gene

Clinical features: glomerulonephritis (microscopic haematuria & proteinuria in childhood, later nephrotic syndrome), ocular disease & deafness to high pitched sounds

2. Fabry’s syndromeRare, X linked recessive syndrome

Glycosphingolipid metabolism, resulting in painful extermities, red hyperkeratotic papules on skin*, proteinura, renal failure

Congenital Nephrotic Syndrome: rare, mesangial proliferation or glomerulosclerosis

Chronic Glomerulonephritis

Chronic 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 hyalinization

Microscopically: hyalinization of glomeruli

Systemic diseases

Systemic lupus erythematosusRenal 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 vasculitis

Affects small arteries in skin, joints, gut, kidneys

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

Diabetic Glomerulosclerosis

Diabetic glomerular damage causes increased permeability of capillaries in the BM, leading to proteinuris and nephrotic syndrome

Pathogenesis: not fully understood, involves deficiency in proteoglycans, glomerular hypertrophy, BM thickening, mesangial cell hypertrophy

Histologically

1) capillary wall thickening – mild proteinuria

2) diffuse glomerulosclerosis

3) nodular glomerulosclerosis

AmyloidosisAmyloid, an extra cellular fibrillar protein* is deposited in tissues, including kidney

Amyloid fibrils deposited in BM, and mesangium

Proteinuria & 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 arteries

Necrosis 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 outcome

It 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 clearance

Prognosis: <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 dysplasia

OutcomesChronic 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 epithelium

Macroscopically: discreet nodules < 20mm diameter in cortex

Microscopically: well differentiated large clear cells

Renal hamartoma: commonest benign tumour of kidney, made of spindle cells

Macroscopically: firm white nodules in medulla, 3-10mm size

Microscopically: spindle cells

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

Renal hamartoma

Malignant tumours of kidney

Renal cell carcinomaAdenocarcinoma made of renal tubular epithelium, in adults

3% of all carcinomas, 90% of primary malignant renal tumours

Males 3:1 females

Associated 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 & necrosis

Microscopically: clear of granular cell types (referring to cytoplasm of cells)

Symptoms: haematuria, loin pain, loin mass

Prognosis: 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 age

3 types identifiedCommonest : 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 mesentery

Microscopically: 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 obstruction

Obstruction of urine drainage from kidney at ANY level within urinary tract

Intrinsic 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, tumours

Pelviureteric junction: strictures, calculi, ext compression

Ureter: calculi, ext compression (pregnancy, fibrosis, tumour)

Bladder neck: tumour, calculi

Urethra: 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> females

Can form anywhere in urinary tract, usually in renal pelvisComposition of stones

Calcium oxalate (80%)

Triple phosphates (15%) magnesium ammonium phosphate stones

Uric 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 calyces

If calcium deposition occurs, nephrocalcinosis

Symptoms:Renal colic* with nausesa & vomitting caused by passage of small stones along ureter

Dull 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

CYSTITIS

Inflammation of bladder

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

AetiologyInfection 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 mucosa

Microscopically: 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 mellitus

Pregnancy

Trauama (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 analysis

Treatment: anit bacterial, antibiotics, flluid therapy

Sequelae:Resolution

Chronicity

Pyelonephritis*

Bladder metaplasia

GLANDULAR 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 TUMOURS

TRANSITIONAL CELL CARCINOMA

Incidence: 1/5000 in UK, 3% of all cancer deaths

Males 3: 1 females, 60-70 years

Aetiology

Chemical: eposure to environmental agents (cigarette smoking, aniline dyes, rubber industry)

Leucoplakia: keratinizing metaplsia, white plaques and calculi

Bladder diverticuli*

Most occur at base of trigone*

Transitional cell CT and histology

MORPHOLOGYPapillary (commonest) warty masses, projecting into lumen with little invasion of bladder wall

Solid: tumours grow directly into bladder wall, often ulcerated

Mixed papillary and solid

Flat in situ carcinoma: reddened mucosa

GRADINGTCC grades I-III

I: well differentiated, no invasion

II: moderately well differentiated, papillary ,atypical cells

III: poorly differentaited, pleomorphic* cells, invasive

Bladder cancer staging

TNM

Tumour-node-metastasis Staging

T1: tumour confined to mucosa or submucosa

T2: superficial muscle involved

T3: deep muscle involved

T4: invasion beyond the bladder

Spread: local to pelvic structures, lymph or haematogenous

Treatment: stage dependeant, diathermy +- radiotheapy, cystectomy or palliative* radiotherapy

Prognosis: 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 PATHOLGIES

MULTIPLE CHOICE AND SHORT ANSWERS

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