nephrotic syndrome Flashcards
what is nephrotic syndrome
collection of signs and symptoms indicating damage to the glomerular filtration barrier
characterised by massive protienuria >3.5g/24 hours
hypoalbuminuria and oedema
common causes of nephrotic syndrome
in adults:
- focal segmental glomerulosclerosis
- membranous nephrotpahy
in children:
- minimal change disease
can also be a manifestation of advanced disease in systemic conditions:
- diabetic nephropathy, amyloid nephropathy
typical lab findings of nephrotic syndrome
hyperlipidaemia and fatty casts on urinalysis
minimal change disease
most common cause of nephrotic syndrome in children
often idiopathic
responds well to prednisolone
good prognosis
focal segmantal glomerulosclerosis
most common cause of nephrotic syndrome in adults
can be idiopathic, or caused by herion use, HIV infection, sickle cell, massive obesity, interferon treatment, congenital malformations
shows poor response to prednisolone
add other immunosuppressants
RAAS inhibitors
usually leads to ESRD if left untreated
RAAS inhibitors
A group of drugs that inhibits the renin-angiotensin-aldosterone system (RAAS). Consists of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and direct renin inhibitors. Typically used in the management of hypertension, heart failure, chronic kidney disease, and myocardial infarction.
membranous nephropathy
primary cause: anti-PLA2R antibodies
secondary cause: infections, autoimmune diseases, tumours, medications
medications: RAAS inhibitors, prednisoline, other immunnosuppressants
usually leads to ESRD if left untreated
dibetic nephropathy
usually additional signs of other organ system complications eg. retinopathy, neuropathy
stringent gycaemic control
RAAS inhibitors
amyloid nephropathy
the kidney is the most commonly affected oragn in systemic amyloidosis
other organs may also be affected eg. the heart
melphalan, corticosteroids
treatment of underlying disease eg. bone marrow transplantation may be used for multiple myeloma
membranoproliferative glomerulonephritis
usually manifests with nephritic sediment which can indicate nephritic-nephrotic syndrome if there is nephrotic range proteinuria or pure nephritic syndrome in there is proteinuria below nephrotic range
why does nephrotic syndrome happen
glomeruli are damaged and become more permeable
plasma proteins can cross from the blood to the nephron and into the urine causing proteinuria
albumin leaves the blood causing hypoalbuminuria
hypoalbuminuria causes low osmotic pressure which drives water out of the blood and into tissues (oedema)
increased levels of lipids in the blood (hyperlipidaemia)
lipids go into the urine as well (lipiduria)
what do podocytes do
charge barrier
negatively charged foot processes that sit on the basement membrane and repel proteins
what happens in minimal change disease
damage to the negatively charged foot processes by cytokines damages the charge barrier so that albumin, but not larger molecules such as immunoglobulins, get through
causing selective proteinuria
why is it called minimal change disease
on light microscopy, the affacement of foot processes is not visible, so it looks like there is no change to the glomerulus
electronmicroscopy can be used to visualise the effacement of foot processes
will immunoflourescence show minimal change disease
no because the damage is due to cytokines not immune complex deposition
treatment of minimal change disease
corticosteorids therapy
90% of children respond well
potential for relapse
features of focal segmental glomerulosclerosis
lipiduria, hyperlipidaemia, oedema, proteinuria
afferent arteriole
arteriole entering the glomerulus
efferent arteriole
arteriole exiting the glomerulus
glomeruli are physically supported by
mesangial cells
how does stuff exit blood and into nephron
through cappilarry wall endothelium, through basement membrane, then through nephron epithelium
pathogenesis of diabetic nephropathy
excess of glucose in the blood because it cant get into cells
excess glucose spills into urine - glycosuria
non enzymatic glycation: glucose sticks to proteins in the blood
glycation of the basement membrane of small blood vessels causing them to thicken
especially effects the efferent arteriole causing it to get stiff and more narrow - obstructing making it difficult for blood to leave the glomerulus
increases pressure within the glomerulus with increases GFR
hyperfiltration
mesangial cells secrete more structural matrix to support the glomerulus
kimmelstiel-wilson nodules
mesangial cells secrete more structural matrix unevenly causing nodules of expansion
key cahnges in diabetic nephropathy
thickened glomerular basement membrane
mesangial expansion
kimmelstiel wilson nodules
disruption of podocytes
eventually damage causes GFR to decrease
symptoms of diabetic nephropathy
typically no symptoms during hyperfiltration phase (when there is increased pressure in the glomerulus increaseasing GFR)
as more nephrons are affected the GFR decreases dramatically
once the kidneys cant filter blood, patient enters end stage renal disease
level of albuminuria in diabetic nephropathy
microalbuminuria: 30-300gm of albumin a day
macroalbuminuria: above 300mg of albumin a day
treatment of diabetic nephropathy
ACEI and ARBs reduce blood pressure but also reduce constriction of the efferent arteriole which reduces pressure in the glomerulus
membranoproliferative GN is triggered by
immune deposits in the walls of the glomerulus, causing inflammation and nephrotic syndrome
type 1 of of MPGN
type 1: circulating immune complexes (maybe from some sort of infection) enter glomerulus and cause classical compliment pathway
alternative complement pathway (C3)
immune deposits recruit inflammatory cells that damage capillary wall and trigger thickening of basement membrane
mesangial cells proliferate and divide (mesangial interposition)
type 2 MPGN
dense deposit disease
IgG antibody (nepphritic factor) stabilises C3 convertase, allowing it to keep converting C3a and C3b
inflammation in the membrane
all types of MPGN present as
nephrotic syndrome
may also present as nephritic syndrome
treatment of MPGN
steroids
all types may progress to chronic renal failure
