Kidney pathology 2010.1

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

• E coli, Proteus, Enterobacter, Klebsiella …

• Abscesses in cortex, 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)• Bacterial adhesins, colonisation, ascending

infection• Cystitis• Vesico-Ureteric Reflux & Intrarenal Reflux,

congenital or acquired– VUR: Urine, bacteria -> ureter– Inrarenal reflux: Urine enters kidney papillae

Predisposing factors

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

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

– If no reflux, infection only in bladder

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 often negative 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