Nephrotic syndrome Flashcards
nephrotic syndrome
4 signs
inflammation and damage of the nephron (podocytes) (loose protein)
group of symptoms without a specific underlying cause.
- peripheral oedema (frothy urine)
- proteinuria >3g/24 hours
- hypoalbuminaemia (serum albumin <256g/L)
- hypercholesterolaemia (dyslipidaemia)
+/- haematuria
+/- loss of immunoglobulins
*predisposed to thrombosis, HTN, high cholesterol
in children: minimal change disease (treat with steroids)
in adults: focal segmental glomerulosclerosis
signs and symptoms of nephrotic syndrome
dyslipidaemia:
xanthelasma
xanthoma
hypoalbuminaemia: tiredness leukonychia oedema (reduced oncotic pressure) periorbital oedema ascites peripheral oedema of the lower limb (SOB)
urine:
frothy (protein)
nephrotic syndrome investigations
diabetic nephropathy
autoimmune problems
urine dipstick
MSU
FBC, EUC, LFT, Ca2+, CRP, glucose. serum and urine immunoglobulins
autoimmune screen
hep b and c
HIV
CXR can show pleural effusoin / oedema
USS of the kidney
Renal biopsy
- light microscopy
- immunofluorescent
- electron microscopy (architecture of the glomerulus)
primary nephrotic syndrome
MMF
- minimal change disease
minimal change in light microscopy
IgM in the mesangium
effacement of podocyte foot processes.
2. membranous glomerulus nephritis nephrotic syndrome in adults renal biopsy mesangial expansion capillary wall thickening IgG and C3 GBM thickening
- focal segmental glomerulosclerosis
renal biopsy- focal segmental glomerular sclerosis
ECM: GBM thickening
secondary nephrotic syndrome
SLE
diabetic nephropathy most common cause
hep B, C, D
amyloidosis
nephrotic syndrome pathophysiology
loss of protein due to damage to the podocytes
- mass proteinuria (protein in urine)
- haematuria
- immunoglobulinaemia
loss of protein stimulates the liver to create albumin and cholesterol. reduced plasma oncotic pressure = water and electrolytes move into the interstitium
this results in peripheral oedema (swelling of the feet)
decrease volume in the circulation = less vol returned to the heart = decrease in blood volume= decrease in renal blood flow = drop in GFR
low renal blood flow stimulates RAAS= results in further oedema (retention of Na+ and H2O)
membranous glomeruonephritis
most common type of glomerulonephritis
There is a bimodal peak in age in the 20s and 60s
Histology shows “IgG and complement deposits on the basement membrane”
The majority (~70%) are idiopathic
Can be secondary to malignancy, rheumatoid disorders and drugs (e.g. NSAIDS)
nephrotic syndrome pathophysiology
affects kidney glomeruli
type of nephrotic syndrome
glomeruli damaged- more permeable- plasma proteins enter the urine (proteinuria >3.5g/day)
hypo albumianemia (lowers oncotic pressure =oedema)
increased levels of lipid in the blood (lipidaemia) (lipiduria)
- proteinura
- hypoalbuminaemia
- oedema
- hyperlipidaemia
- lipiduira
minimal change disease
endothelial cells - basement membrane - foot procesess. foot processes- negatively. charged.
T cells release cytokines which damage the podocytes (effacement -flattened out) selective proteinuria.
causes: idiopathic. associated with Hodgkin’s lymphoma (general increase in cytokine production) or drugs (NSAIDs and lithium)
diagnosis:
- light microscopy and H&E stain so ‘minimal change’
- electron microscopy shows effacement of foot processess.
- immunoflurocence is -ve
treatment: corticosteroid therapy. prednisolone 4-16 weeks.
focal segmental glomerulosclerosis
some segments of some glomeruli are affected with sclerosis.
proteins filter through to the urine- develop nephrotic syndrome.
protein plasma and lipids filter into the urine due to damage of the podocytes. build up in the glomerulus = hyalinosis (glassy appearance on histology)= develops into scar tissue.
can be the end result of lots of different pathological processess.
- sickle cell disease
- HIV- associated nephropathy
- heroin nephropathy
- kidney hyperperfusion and increased pressure in glomerular capillaries.
diagnosis:
histology- segmental sclerosis and hyalinosis
electron microscope- effacement of foot processess.
immunofluoresence
non specific focal deposits of IgM and complement
list of all nephrotic syndromes
- lupus nephritis
- minimal change disease
- focal segmental glomerulosclerosis
- diabetic nephropathy
- membrano prolfierative glomerulonephritis
- membranous glomerulonephritis
membranous glomerulonephritis
membranous nephropathy
glomerular basement membrane becomes inflamed and damage.
caused by immune complex (antigen-antibody) (auto antibodies targeting the GBM= M type phospholipase A2 receptor and neutral endopeptidase)
can form outside of the kidney and then deposited in the GBM= cationic bovine serum albumin.
- sub-epithelial deposits
- activates the complement cascade.
- damages the podocytes and mesangial cells
- damages the GBM
- GBM matrix becomes deposited= thickened on histoloy.
electron microscopy ‘spike and dome pattern’ and ephacement of the podocytes.
immunofluroscent: granular deposition of complex
tx: steroids
membranoproliferative glomerulonephritis
MPGN
a type of nephrotic syndrome
3 types
type 1: circulating immune complex (antigen released from chronic infection). bind to glomerulus= activate the complement pathway
inappropriate activation of the alternate complement pathway. thickening of GBM and mesangial cell proliferation. (mesangial interposition)
type 2:
only complement deposits (no immune complex) ‘dense deposit disease’
type 3:
deposits in subendothelial and subepithelial space.
symptoms:
protein in urine and can also present as a nephritic syndrome (inflmmation= haematuria, oligouria, azotemia, HTN)
treatment: steroids
lupus nephritis
inflammation of the kidney from having lupus
some cells DNA is badly damaged= apoptosis= exposes inside of the cells (DNA, histones, proteins) to the body. the immune system mistakes these nuclear antigens for foreign = attack.
antigen-antibody complex deposit in the kidneys and initiate an inflammatory reaction (type III hypersensitivity)
- majority of cases= nephrotic syndrome (proteinuria)
- some cases can be nephritic (blood in urine)
biopsy: crecent shaped swelling, wire loop pattern
tx: corticosteroids, meds for lupus (mycophenolate, cyclophosphamide)
diabetic nephropathy
pathophysiology
kidney damaged caused by type I and II DM
leading cause of end-stage renal disease.
- glucosuria
- (glucose sticks to protein= non enzymatic glucosation)
- glycation of the Basement membrane= thickens.
- stiffening of the efferent arteriole (hyaline arteriosclerosis causes obstruction to blood flow)
- afferent arteriole dilates
- increase in eGFR= hyperfiltration
- thickened glomerular BM
- mesangial expansion]
- kimelsteil wilson nodules
- disruption of podocytes
eGFR eventually decreases
