nephrotic syndrome

Question 1

what is nephrotic syndrome

Answer 1

collection of signs and symptoms indicating damage to the glomerular filtration barrier
characterised by massive protienuria >3.5g/24 hours
hypoalbuminuria and oedema

Question 2

common causes of nephrotic syndrome

Answer 2

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

Question 3

typical lab findings of nephrotic syndrome

Answer 3

hyperlipidaemia and fatty casts on urinalysis

Question 4

minimal change disease

Answer 4

most common cause of nephrotic syndrome in children
often idiopathic
responds well to prednisolone
good prognosis

Question 5

focal segmantal glomerulosclerosis

Answer 5

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

Question 6

RAAS inhibitors

Answer 6

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.

Question 7

membranous nephropathy

Answer 7

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

Question 8

dibetic nephropathy

Answer 8

usually additional signs of other organ system complications eg. retinopathy, neuropathy
stringent gycaemic control
RAAS inhibitors

Question 9

amyloid nephropathy

Answer 9

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

Question 10

membranoproliferative glomerulonephritis

Answer 10

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

Question 11

why does nephrotic syndrome happen

Answer 11

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)

Question 12

what do podocytes do

Answer 12

charge barrier
negatively charged foot processes that sit on the basement membrane and repel proteins

Question 13

what happens in minimal change disease

Answer 13

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

Question 14

why is it called minimal change disease

Answer 14

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

Question 15

will immunoflourescence show minimal change disease

Answer 15

no because the damage is due to cytokines not immune complex deposition

Question 16

treatment of minimal change disease

Answer 16

corticosteorids therapy
90% of children respond well
potential for relapse

Question 17

features of focal segmental glomerulosclerosis

Answer 17

lipiduria, hyperlipidaemia, oedema, proteinuria

Question 18

afferent arteriole

Answer 18

arteriole entering the glomerulus

Question 19

efferent arteriole

Answer 19

arteriole exiting the glomerulus

Question 20

glomeruli are physically supported by

Answer 20

mesangial cells

Question 21

how does stuff exit blood and into nephron

Answer 21

through cappilarry wall endothelium, through basement membrane, then through nephron epithelium

Question 22

pathogenesis of diabetic nephropathy

Answer 22

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

Question 23

kimmelstiel-wilson nodules

Answer 23

mesangial cells secrete more structural matrix unevenly causing nodules of expansion

Question 24

key cahnges in diabetic nephropathy

Answer 24

thickened glomerular basement membrane
mesangial expansion
kimmelstiel wilson nodules
disruption of podocytes

eventually damage causes GFR to decrease

Question 25

symptoms of diabetic nephropathy

Answer 25

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

Question 26

level of albuminuria in diabetic nephropathy

Answer 26

microalbuminuria: 30-300gm of albumin a day
macroalbuminuria: above 300mg of albumin a day

Question 27

treatment of diabetic nephropathy

Answer 27

ACEI and ARBs reduce blood pressure but also reduce constriction of the efferent arteriole which reduces pressure in the glomerulus

Question 28

membranoproliferative GN is triggered by

Answer 28

immune deposits in the walls of the glomerulus, causing inflammation and nephrotic syndrome

Question 29

type 1 of of MPGN

Answer 29

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)

Question 30

type 2 MPGN

Answer 30

dense deposit disease
IgG antibody (nepphritic factor) stabilises C3 convertase, allowing it to keep converting C3a and C3b
inflammation in the membrane

Question 31

all types of MPGN present as

Answer 31

nephrotic syndrome
may also present as nephritic syndrome

Question 32

treatment of MPGN

Answer 32

steroids
all types may progress to chronic renal failure