Week 15 Pathology

Acute renal failure:

Pre renal causes

Hypovolaemia, hypotension, CCF –> poor renal perfusion–> decreased renal clearance of toxins and ischaemia of tubular cells

Intra renal causes

Systemic Diseases with Glomerular Involvement
- HTN –> focal segmental glomerulosclerosis
- DM –> tubulointerstitial fibrosis, hyalinizing arteriolar sclerosis, papilary necrosis.
- immunological – SLE, good pastures, wegners, HSP (rapidly progressive, crescents), microscopic polyangitis
- Amyloidosis

Hereditary Disorders
- Alport, Fabry
Nephritic syndrome – haematuria, uremia, variable proteinuria, oliguria, oedema and HTN
Nephrotic syndrome – Proteinuria(>3.5g), hypoalbuminaemia, hyperlipidaemia, lipiduria.

Major Changes observed in Glomerular diseases
- Histological changes – hypercellularity, BM thickening, Hyalinisation/sclerosis,
- Ab-Ag complex deposit mainly subendothelially
- antiGBM deposit in GBM
- Heymann – antibody to ag in epithelial cell.
- Ab –> cytotoxic injury and complement mediated injury –> epithelial cell foot process effacement and detachment–> increased leakage into urine of blood components.

Disease	Pathogenesis	Glomerular Pathology	Most Frequent Clinical Presentation
Post strep	Circulating or planted antigen	IgG and C3 in GBM	Acute nephritis
Good pastures	Anti GBM	Proliferation, cresents	Rapidly progressive GN
Membranous	Insitu Ab mediated	Diffuse cap wall thickening	Nephrotic syn
Minimal change	Podocyte injury	Normal, lipid in tubule	Nephrotic syn
Focal segmental	Unknown	Focal and segmental sclerosis and hyalinosis	Nephrotic syn
Membrane proliferative	Immune complex	Mesangial proliferation, BM thickening	Nephrotic syn
Ig A nephropathy	Unknown	Focal proliferative GN	Recurrent haematuria or proteinuria
Chronic GN	Variable – mainly rapidly progressive and focal glomerulosclerosis	Hyalinized glomeruli	Chronic renal failure

Post renal causes (Causes of urinary obstruction) –> back flow –> renal damage and decreased function.

From the presentation by Prof Nabil Tadros Mikhail.

Commonest cause of AKI – 50%
Destruction of tubular epithelial cells and acute renal failure
Causes
- Ischaemia, hypoperfusion
- Direct toxic injury – contrast, radiation, gentamycin
- Acute tubulointerstitial nephritis -hypersensitivity to drugs
- DIC
- Urinary obstruction
Necrosis is more in PCT and PST in toxic type and less in ischaemic type. Both have casts from DCT to CD.
Clinical course
- Initiation: 36hrs, slight decrease in UO and rise in blood urea.
- Maintanence: sustained oliguria, rising Urea and creatinine, hyper K, metabolic acidosis, uraemia – needs supportive mangement to carry pt over this
- Recovery: increasing UO, tubules still damaged so large amount of water and electrolytres lost – Hypo K, increase risk of infection, everything normalises eventually.

Causes
- Haematologenous – Staphylococcus, E Coli
- Ascending – E Coli, Proteus, enterobacter
Consequences
- Dysuria, frequency
- Pyelonephritis – flank pain, fever, acute renal failure.
Predisposing factors
- Female – short urethra
- Vescioureteric reflux – shallow angle of ureter insertion.
- Instrumentation of urinary tract
- Pregnancy
- DM
- Immunosuppression

Childhood type – associated with bloody diarrhoea caused by intestinal infection by verocytotoxin releasing bacteria
Adult
- Infection- typhoid, ecoli, shigellosis
- Antiphospholipid Abs
- Cx of preg and contraceptive
- Vascular renal disease eg HTN, scleroderma
- Chemo and immunosuppressive drugs
- Radiation
Mechanism: endothelial injury–> activation–> intravascular thrombosis–> platelet aggregation–> distal ischaemia

Fever, neurological sx, haemolytic anaemia, thrombocytopenic purpura, thrombi in glomeruli.
Gene defect in ADAMTS-13–> affect cleavage of vWF –> promotion of platelet aggregation.
Women, younger than 40
Neurological sx are dominant.