Renal Path Flashcards
Syndromes of Renal Injury
1) Acute kidney injury
2) Nephrotic syndrome
3) Isolated urinary abnormality
4) Chronic kidney disease / renal failure
Definition and Causes of Acute Kidney Injury
Definition: Rapid loss of glomerular filtration and renal function manifesting as increase in serum creatinine and urea
May result in acidosis, hyperkalaemia and fluid overload (hypertension)
Pre-Renal: loss of perfusion
Can be:
Generalised –> shock
Local –> renal artery occlusion
Renal
Acute tubular injury
Acute Glomerulonephritis
Thrombotic microangiopathy
Post-Renal
Obstruction of urine outflow
/reflux
Acute Tubular Injury
Acute tubular injury is a renal cause of AKI
Commonest cause of acute renal failure
Caused by damage to tubular epithelial cells by ischaemia or toxins e.g. drugs, myoglobin
Drugs that inhibit vasodilatory protaglandins e.g. NSAIDS predispose
Tubular cells die and fall into tubules –> Granulocasts
These casts block tubules –> Leakage of fluid from tubules to interstitium reducing flow —> Secondary haemodynamic changes – feedback form each distal tubule to macula densa, when blood flow falls through the tubules this triggers reduction in filtration
Acute Glomerulonephritis
Acute glomerulonephritis is a renal cause of AKI
Acute inflammation of glomeruli –> reduction in GFR
Red and white cell casts in urine
Can present with oliguria
Glomerular crescents=infiltration of inflammatory cells into Bowman’s space
Causes of Cresenteric Glomerulonephritis
Immune Complexes
Anti-GBM disease (Goodpastures)
Pauci-immune (ANCA assoc.)
Immune Complex Associated Glomerulonephritis
Is a renal cause of AKI, of which it causes cresenteric glomerulonephritis
This is when immune complexes deposit in glomerulus (either sub-endothelial, sub-epithelial or mesangial deposits) –> inflammatory infiltration into Bowman’s Capsule
Causes
SLE
IgA nephropathy
post-infectious GN
Immune complexes can be identified by GRANULAR DEPOSITION on immunohistochemistry
Goodpasture’s (Anti-GBM)
Is a renal cause of AKI, of which it causes cresenteric glomerulonephritis
Antibody against Type IV collage in BM
Causes immune activation in lung and glomeruli –> lung haemorrhage and glomerulonephritis
IgG mediated
Immune complexes can be identified by LINEAR DEPOSITION on immunohistochemistry
Pauci-immune Glomerulonephritis
Is a renal cause of AKI, of which it causes cresenteric glomerulonephritis
Scanty deposits of of immunoglobulin and complement are present in glomeruli
ASSOCIATED WITH cytoplasmic antibodies ANCA
ANCA –> neutrophil activation leading to glomerular necrosis
ASSOCIATED with vasculitis e.g skin rash, lung haemorrhage
Thrombotic Microangiopathy
Is a renal cause of AKI
Caused by damage to endothelim within glomeruli –> thrombus formation in small arterioles
Red blood cells may become damaged by fibrin leading to haemolysis – microangiopathic haemolytic anaemia
Syndrome therefore referred to as haemolytic uraemic syndrome (HUS)
See SCHISTOCYTES on blood film
TWO forms Diarrhorrea associated Caused by GI infection with E. coli Releases toxin that targets the renal endothelium "Petting Zoo" buzzword
Non-diarhorrea
Abnormalities of proteins that control activation of the complement pathway on endothelium
May be familial
Non-diarrhoea aka atypical HUS
Monoclonal antibody against complement component C5 is very effective in treating atypical HUS
Nephrotic Syndrome
Breakdown of selectivity of the glomerular filtration barrier leading to massive protein leak
Characterised by:
Proteinuria > 3.5g/day
Hypoalbuminaemia
Oedema
Hyperlipidaemia
CAUSES SYSTEMIC Diabetes mellitus (most common) Amyloidosis (Stains with Congo red stain and looks green under polarised light) Buzzword SLE
PRIMARY glomerular disease: affects podocyte
Minimal change disease (most common in children)
Focal and segmental glomerulosclerosis
Membranous glomerulonephritis
Amyloidosis
Is a cause of nephrotic syndrome, of which it is a systemic (i.e. not a primary) cause
Extracellular protein deposition
Insoluble –> Damaged tissue
Stains with Congo red stain and looks green under polarised light = Buzzword
May be derived from many precursor proteins. Commonest forms in kidney are:
AA
derived from serum amyloid associated protein (SAA)
SAA is an acute phase protein which is increased in chronic inflammatory conditions e.g rheumatoid arthritis, chronic infections.
AL
Derived from immunoglobulin light chains
80% of patients have multiple myeloma.
L= light-chain
Minimal Change Disease
Primary glomerular cause of nephrotic syndrome
Glomeruli look normal apart from effacement of foot processes on EM
Common cause of nephrotic syndrome in children
Generally responds to immunosupprssion
Children with nephrotic syndrome get prednisolone,
If doesn’t improve –> biopsy
Focal and Segmental Glomerulosclerosis
Primary glomerular cause of nephrotic syndrome
Appears similar to minimal change disease with loss of effacement of podocyte
BUT, also develop segmental scars
Less responsive to steroids
Membranous Glomerulonephritis
Primary glomerular cause of nephrotic syndrome which itself can be categorised into primary and secondary causes
Associated with immune deposits on the outside of the glomerular basement membrane affecting podocytes
CAUSES
Primary – many associated with antibodies to phospholipase A2 receptor (phospholipase A2 receptor is present on podocyte)
Secondary SLE Infection Drugs Malignancy
Isolated urinary abnormality
Microscopic haematuria
Thin basement membranes
Hereditary defect in type IV collagen
In most cases microscopic haematuria is the only consequence
IgA nephropathy
Commonest form of glomerulonephritis worldwide
Predominant IgA deposition in glomeruli
Often presents with microscopic or macroscopic haematuria
May cause proteinuria, acute renal failure
Up to 30% progress to end stage renal failure
Asymptomatic proteinuria
May be associated with a wide range of glomerular structural abnormalities or immune complex deposition
Diagnosis often requires renal biopsy
Causes of Chronic Kidney Disease
CAUSES Diabetes (19.5%) Glomerulonephritis (15.3%) Hypertension & Vascular disease (15%) Reflux nephropathy (chronic pyelonephritis) (9.5%) Polycystic kidney disease (9.4%)
