nephrotic proteinuria + haematuria … the worst prognosis
Nephrotic syndrome = c linical complex consisting of:
Proteinuria of > 3.5g / 1.73m 2 / 24 hours
Patophysiology of the nephrotic syndrome . Primary insult- increased glomerular permeability, causing plasma protein leakage into urine. Hypoalbuminemia is the cause of the main clinical features.
Metabolic albumin turnover in healthy subjects vs. subjects with nephrotic syndrome .
?? The “ underfill ” mechanism of edema formation. In this theory, hypovol e mi a ( caused b y hypoalbuminemia and decreased oncotic plasma pressure) is the main cause of renal Na + a H 2 0 retention.
?? The “ overfill ” mechanism of edema formation. In this theor y , a bnorm a l renal Na + a nd H 2 0 retention is the main cause of Starling forces alteration at local tissue level.
(Possible) consequences of proteinuria and lipid spectrum abnormalities.
Diagram showing pathogenetic factors leading to hypercoagulability , tromboembolism and renal vein thrombosis.
Causes of nephrotic syndrome
Treatment of nephrotic syndrome
NaCl, H 2 0 restriction
Specific (depending on the causative disease)
in amyloidosis, treatment of the causative process
Treatment and prevention of complications
lipid metabolism disturbances
Ineffective: high protein diets, albumin supplementation.
Glomerular inflammatory changes leading to
h a ematuria (red cell casts).
Typical example: Poststreptococcal glomerulonephritis in children
Differences between nephrotic and nephritic syndromes normal/low normal glomerular filtration normal/slightly decreased low serum albumin present not present red cell casts +++ present/not present hematuria ++ ++++ proteinuria increased normal/low central venous pressure increased normal arterial blood pressure ++ ++++ swelling acute slow onset Nephritic syndrome Nephrotic syndrome Typical features
Histology (light micros c opy) of acute poststreptococcal GN (marked invasion of polymorphonuclear cells)
Histology of acute poststreptococcal GN (subepithelial hump-like deposits (strait arrows), sube ndothelial (arched arrows) and mesangial deposits) . E ndocapillary hypercellularity caused by neutrophil infiltration, endothelial and mesangial proliferation .
Immunological findings in poststreptococcal GN
1. The serial estimation of complement -
Early in the acute phase, the levels of hemolytic complement activity (CH50 and C3) reduced .
Within 8 weeks return to normal
2. Serial ASO titer measurements - twofold or greater rise in titer are highly indicative of a recent infection.
C ontinu ous alterations of structural changes caused by glomerular inflammation (upper part), clinical syndromes (middle part) and specific nosologic units (lower part).
Rapidly progressive GN (RPGN)
Severe glomerular disorder -> ↓ glomerular filtration in days or weeks.
Clinical features: acute uremic or nephritic syndrome with renal insufficiency rapidly -> renal failure
Histology: negative IF (pauci-immune), crescentic GN (crescent = half-moon-shaped lesion in Bowman ’s space composed of proliferating parietal epithelial cells and infiltrating monoc ytes). Crescentic GN: > 70% glomeruli are involved.
Toxic Sequelae of Metabolic Acidosis Organ Mechanism -> Sequelae Muscle Proteolysis -> Loss of lean body mass Bone Inhibition of osteoblasts -> Dissolution of bone matrix Stimulation of osteoclasts -> Dissolution of bone mineral Hormonal PTH level -> Osteopenia Vitamin D3 -> Osteomalacia Cortisol -> Activation of catabolism Thyroxine -> Hypometabolism Growth hormone -> Stunted growth ↑ Insulin resistance -> Activation of catabolism