renal pathology tutorial

Histopath Tutorial 2: Renal PathologyChristiane Riedinger 6/3/14

Today’s Contents● organising renal pathology● major symptoms of renal pathology● kidney failure (acute kidney INJURY, chronic renal DISEASE)

○ acute vs. chronic○ causes, clinical phases

● sites of renal pathology○ glomeruli○ tubules○ interstitium○ collecting system

● biochemical abnormalities

Today’s Contents● organising renal pathology● major symptoms of renal pathology● kidney failure




Overview of Renal Pathology

● many different ways of organising this topic

● mnemonic

● hereditary vs. acquired

● structure/anatomy

● outcome: acute vs. chronic

Overview of Renal Pathology ctnd.

● mnemonic - surgical sieve: (e.g. A vitamin CDE)● Acquired: Diabetic kidney disease● Vascular: Particularly susceptible, renal artery stenosis, arterionephrosclerosis,

hypertension● Infectious: nephritis (glomeruli vs. tubules, potentially post-infectious), TB,

abscesses● Trauma: shock● Autoimmune: Particularly susceptible, SLE, vasculitides, amyloidosis● Malignant: benign tumours, tubular or transitional cell carcinoma, nephroblastoma● Idiopathic: many glomerulonephritides, e.g. minimal change● Neoplastic: renal carcinoma, Wilm’s tumour, multiple myeloma● Congenital: PKD, Alport’s, Fabry’s, von Hippel-Lindau● Drugs: toxicity


http://www.baileybio.com/plogger/?level=picture&id=1486

http://www.sclerodermasociety.co.uk/Theheartandscleroderma1.php

● structure/anatomy

macroscopicglomerulus

tubule

vessels

tubulo-interstitial

collecting system

systemic


● outcome:

acutevs.

chronickidney failure

1* Symptoms of Renal Pathology● haematuria

○ with or without symptoms○ microscopic or macroscopic

● proteinuria○ via leakage - glomerular damage○ defective reabsorption in tubules

■ heavy metal damage■ Fanconi syndrome■ Hartnup disease AA absorption disease

○ overflow■ haemolysis■ intravascular haemolysis

● NEPHRITIC (both) vs NEPHROTIC syndrome (prOtein Only)● oligo/anuria● renal pain● endocrine changes

1* Symptoms of Renal Pathology ctnd.

● always also think about what is happening in the blood, not just the urine!● nephritic syndrome

○ haematuria○ proteinuria○ in blood: azotemia○ oedema, hypertension

● nephrotic syndrome○ proteinuria○ lipiduria○ in blood: hypoalbuminuria, hyperlipidaemia○ oedema○ increased clotting○ risk of infection

Kidney Failure: DefinitionsAcute deterioration in kidney function (over <48h) with increase in creatinine (>0.3mg/dL) and decrease in urine output (<0.5mL/kg/h).

Long-term degeneration of kidney function defined by persistently low or decreasing GFR or abnormal structural or functional findings.

Kidney Failure: Causes (acute)● pre-renal

○ all vascular + contents of vessels○ low blood volume○ low BP○ CHF○ renal artery stenosis○ ischaemia○ renal vein thrombosis

● renal○ glomerulonephritis (deposition, vasculitis)○ acute tubular necrosis (toxins, antibiotics, contrast)○ acute interstitial nephritis (distal obstruction)

Kidney Failure: Causes (acute) ctnd.

● post-renal: think OBSTRUCTION!○ again many ways to organise e.g. extrinsic vs intrinsic, here: structural○ parenchyma

■ clot■ mass■ papillary necrosis

○ ureters■ kidney stones■ AAA■ retroperitoneal fibrosis

○ bladder■ bladder stone, tumour, clot■ neurogenic bladder

○ prostate■ BPH■ prostate carcinoma

○ urethra■ stone■ stricture

Kidney Failure: Causes (acute) ctnd.

● summary:

80% pre-renal and tubular necrosis

(other statistics: 85% ATN, 10% interstitial nephritis, 5% GN)

Kidney Failure: Causes (chronic)● diabetes mellitus 30%● hypertension 15%● glomerulonephritis 25%

● together 75%!!!!!● vascular: renal artery stenosis, vasculitis, HUS● infectious: HIV nephropathy, parasites● toxins● congenital: Alport’s syndrome, Fabry’s disease, Polycyst. kidney d. (5%)● systemic (see earlier slide)● post-renal obstruction (see earlier slide)

Kidney Failure: Causes (chronic) ctnd.

● summary:

75% diabetes, hypertension, GN

Kidney Failure: Acute v. chronic summary

Sites of Renal Pathology

The Glomeruli:Glomerulonephritis

Glomerular Pathogenesis

Think DEPOSITION and VASCULAR!

Glomerular Pathogenesis: DEPOSITION ● immune complexes

● glycoprotein deposition, glycation

● amyloid deposition

● paraprotein deposition (MM)

Glomerular Pathogenesis: IMMUNE COMPLEXES ● whole immune complexes get trapped

○ 3 locations: ■ mesangium■ between endothelium and GBM■ between GBM and podocytes

○ (GRANULAR PATTERN)

● in situ reaction○ ABs attack “planted’ non-glomerular antigens

■ SLE nucleosomal complexes, bact. products, protein aggregates

○ ABs attack glomerular AGs (LINEAR PATTERN)■ anti-GBM, anti-podocyte

Glomerular Pathogenesis: IMMUNE COMPLEXES

Glomerulonephritis: DISTINGUISH

● global vs. segmental (entire glomerulus or part)

● diffuse vs. focal (all glomeruli or patches)

● proliferative vs. non-proliferative (proliferation of endothelial and/or

mesangial cells, often a result of inflammation, but does not have to be. I

don’t think BM thickening counts as proliferative)

● nephrotic, nephritic syndrome or both? (how big are the holes?)

● pathological entity vs. clinical syndrome!

Glomerulonephritis

The following slide is the way I have organised GNs to memorise them more easily - it may not be the best/most

correct way as different books group them differently. For resources used see my Histopath notes.

(post-)infectious GN

global, diffuse!

Histology of Glomerulonephritis● note: For an excellent overview, also see Wheater’s Basic Pathology Chapter 15 page 180ff

post-infectious GN membranous GN membranoprolif. GN crescenteric GN

note: GN can cause ischaemia which then causes tubular injury!


The Tubules:(Acute) Tubular Necrosis

Pathogenesis of Tubular Necrosis

f


The Interstitium

Tubulointerstitial Pathology


The Collecting System:Kidney Stones

Path. of the Collecting System: STONES!

● 80% Calcium oxalate - absorptive hypercalcinuria● 10% Magnesium/Ammonium phosphate - alkaline urine from UTIs● <10% uric acid or cystine - urate from gout

- cystine from defect in transport● all stones contain 2.5% mucoprotein

● stone formation around nidus, e.g. bacterial debris or desquamated epithelium

● blockage of urine flow => hydronephrosis:compression => tubules affected => can’t concentrate urine => even more urine!!Therefore polyuria if partial obstructionAnuria if complete and bilateral (80% of stones unilateral)

Biochemistry of Renal Disease

● think about what kidney does and then derive it!● In general potential abnormalities in the following tests

○ urine■ output■ urinalysis■ electrolytes■ creatinine■ osmolality■ Bence-Jones■ culture

○ special■ GFR■ tubular function

○ imaging■ US, CT, MRI■ radioisotope scan

○ pathology■ biopsy

○ immunology○ ECG!

○ blood■ FBC ■ U&E ■ BUN ■ LFTs

■ ESR/CRP■ clotting screen■ CK

Biochemistry of Renal Disease: prerenal

INADEQUATE PERFUSION = ACCUMULATION/RETENTION

● urea => uraemia => U&E’s● creatinine => U&E’s+● H+ => acidosis => U&E’s, ABG?● compounds containing N => azothemia => BUN, BUN/Cr● anuria/oliguria/polyuria => urine output● changes in GFR => GFR● activation of RAAS => Na+ retention => U&E’s, urine

blood: hi Na+,also hi K+?urine: low Na+

Biochemistry of Renal Disease: renal

REDUCED FUNCTION => ELECTROLYTE IMBALANCE AND LEAKAGE

● opposite of RAAS => Hyponatraemia => U&E’s(Na+ loss) hyperkalaemia

● retention of H+ => metabolic acidosis => ABGretention of phosphate => hyperphosphataemia => U&E’s

● retention of Mg2+ => hypermagnesaemia => U&E’s● proteinuria => urinalysis● haematuria => urinalysis● anuria/oliguria/polyuria => urine output

Biochemical abnormalities: chronic kidney d.

● initially compensated ● one nephron hypothesis of Bricker 1960:

○ as nr of nephrons decrease, remaining nephrons must perform greater fraction of total renal excretion

● disturbances we mentioned in previous slides● starts with polyuria● endocrine effects

○ hyperphosphataemia/hypocalcaemia => renal osteodystrophy ○ decreased calcitriol cynthesis○ decreased T, Oe○ thyroid abnormalities○ disorders of glu metabolism○ anaemia○ dyslipidaemia

The end.

renal pathology tutorial

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