Kidney pathology. 1

Tubular & interstitial diseases

Kidney - cut surface• Outer cortex (Co)• Inner medulla

composed of pyramids *

• Cortical columns of Bertini (B) between pyramids*

• Urine first collects in calyces, pelvis

*Co

B

Calyx

*

Pelvis

Malpighi and Malpighian “corpuscles” (glomeruli)

Glomerular structure

• Arterioles• Capillaries• Mesangium (“between

capillaries”)• Urinary space

surrounds glomerulus within Bowman’s capsule

• Urin sp -> prox tubule

Normal renal tubules

Acute pyelonephritis

• Most severe end of spectrum of UTI• Acute bacterial inflammation of kidney

including pelvis (pyelo- )• E coli, Proteus, Enterobacter, Klebsiella …• Abscesses in cortex and medulla• Polymorphs in tubules; glomeruli spared• (CMV, polyoma virus in immunocompromised)

Acute pyelonephritis

Acute pyelonephritis

Acute pyelonephritis - clinical

• M < 1yr and over 40 yrs; F 1 - 40 yrs• Sudden onset tenderness in costo-phrenic

angle• Temp, rigors, cystitis• Most resolve quickly• May recur, become chronic• Complications

Pathogenesis of acute pyelonephritis

• (Haematogenous spread)• Adhesins, colonisation, ascending infection• Short female urethra• Cystitis• Vesico-Ureteric Reflux & Intrarenal Reflux,

congenital or acquired

Predisposing factors

• Short female urethra• Obstruction (pregnancy, congenital, stones,

tumours, BPH)• Bladder dysfunction• Diabetes• Catheters, cystoscopy, other• Vesico-Ureteric Reflux & Intrarenal Reflux

Complications of Acute Pyelo

• Perinephric abscess• Pyonephrosis• *Papillary necrosis• Fibrous scars, chronic

pyelonephritis

Chronic pyelonephritis

• Scars overlying distended calyces• Chronic inflammation and fibrosis

involving tubules and interstitium• Two types

– Reflux nephropathy– Chronic obstructive pyelonephritis

Reflux nephropathy

• Commoner• VUR pressure threshold• Organisms• Refluxing papillae at

upper, lower poles• Hypertension at 15-25 yrs

Chronic pyelonephritis (reflux)

Chronic pyelonephritis - reflux type

Chronic pyelonephritis, obstructive

• Older patients• Strictures, calculi in

ureter, renal pelvis• BPH• Tumours

Chronic pyelonephritis - clinical

• Chronic renal failure, hypertension • UTI (but few positive urine cultures)• Interstitial fibrosis, tubular atrophy,

thyroidization of tubules, thick arteries, FSGS• Accounts for 10 - 20% of patients on dialysis• Other types of pyelonephritis

TB (L) & Xanthogranulomatous PN (R)

Non-bacterial inflammation of renal tubules, interstitium

• Drugs/toxins: penicillins, rifampicin, NSAIDs…..– Immune injury (types I, IV); direct, unknown– Fever, oliguria in 50%, rash– Micro; inflammatory cells, inc eosinophils

• Analgesic nephropathy - phenacetin, +/- aspirin, codeine• Assoc with glomerular disease e.g. SLE, renal vasculitis• Gout, multiple myeloma• Renal allograft rejection

Acute interstitial nephritis

Eosinophils in drug induced interstitial nephritis

Acute renal transplant rejection

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Acute renal failure

• Sudden onset of oliguria (<400ml) – Raised serum Creatinine

• Cause determines symptoms, prognosis • Overall mortality is 40%

– Drugs, toxins– Crescentic glomerulonephritis e.g. ANCA+ vasculitis– Genitourinary obstruction– Shock, ischaemia

Acute renal failure - pathology

• Most patients have a microscopic lesion - Acute Tubular Necrosis (necrosis of tubular epithelial cells is a “marker” of acute loss of renal function)

• Renal tubular epithelium sensitive to toxins, ischaemia• Vasoconstriction -> hypoxia in outer medulla• Two types of ATN: • ATN due to drugs, toxins - PCT cells (95% survival)• ATN due to ischaemia, shock or sepsis - granular casts

(20-50% survival)

Normal tubules (L) and drug-induced ATN* (R)

*

ATN, drug-induced

ATN due to toxin

ATN due to Sepsis/Ischaemia

Interstitial fibrosis and tubular atrophy in chronic renal disease correlate with progressive loss of renal function

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Chronic renal failure

• Progressive and irreversible loss of renal tissue• Chronic GN, chronic PN, hypertensive nephrosclerosis,

diabetes, adult type PCKD• Symptoms - anaemia, dehydration, nausea, metabolic bone

disease, etc• Asymptomatic renal insufficiency present prior to this

while kidneys’ intact nephrons compensate • Dialysis, transplant or death within 1 year of onset of CRF