Nephrology: Nephritic and Nephrotic Syndromes Flashcards
What are the 3 components of the Glomerular Filtration Barrier?
- Fenestrated capillaries – controls blood flow
- Glomerular basement membrane – proteins that make this up are negatively charged to repel large plasma proteins such as albumin and globulins
- Podocytes – have filtration slits to allow certain molecules to permeate
What molecules does GFB block the passage of?
RBC WBC Protein
What is damaged in Nephritic syndrome?
Glomerular basement membrane damage causing a leakage of RBC, WBC and proteins (sub nephrotic range)
What is the difference in proteinuria between nephritic and nephrotic syndrome?
Proteinuria in nephritic syndrome is less than 3.5g\day while in nephrotic syndrome it is more than 3.5g\day
In Nephritic syndrome there would be no albuminuria, antithrombin 3 or immunoglobulins (antibodies)
What are the characteristics of Nephritic Syndrome?
Haematuria (cola coloured urine) (RBC casts or acanthocytes)
Hypertension (mild)
Proteinuria (<3.5g/day)
Oliguria
Sterile Pyuria
Slight edema (periorbital puffiness, would be less than nephrotic coz less protein loss?) and salt retention
JVD
What type of edema is caused by nephritic syndrome?
Mild edema, periorbital or generalise. Would be less than nephrotic
What is sterile pyuria?
Sterile pyuria is a type of pyuria with no bacteria present in urine. Typically, pyuria is WBC or pus in the urine indicating an infection
In sterile pyuria leukocyte esterase, nitrites and bacteria would be negative but there would be a lot of pyuria
What are RBC casts? What are acanthocytes?
RBC casts are formed when RBC get stuck in kidney tubules, taking on its shape becoming cylindrical and red or orange-yellow colour
Acanthocytes are irregular shaped RBC with spikes also known as spur cells
In nephritic syndrome you get a lot of WBC, proteins, and cytokines in the Bowman’s space. What is the complication of this?
These 3 types of cells promote fibrosis, sclerosis, and epithelial cell proliferation (particularly in the parietal layer. Visceral layer is the podocytes).
Proliferation of the parietal layer causes scarring and fibrosis which can lead to a crescent formation it suggests renal failure (crescent formation -> rapidly progressive glomerular nephritis -> renal failure) as GFR is decreased causing oliguria.
What are the complications of low GFR?
Oliguria, increased BUN, creatinine in blood causing azotemia and uremia.
Activates RAAS causing hypertension
Causes of Nephritic syndrome?
Review on notes its a lot
What diseases can have nephritic syndrome with nephrotic range proteinuria?
Lupus nephritis and membranoproliferative glomerulonephritis
What is the difference between type 1 and 2 membrane-proliferative glomerulonephritis?
Type 1 doesn’t have any specific antibody that is deposited while in type 2 it is specific antibody which is nephritic factor
What is the sign of MPGN on biopsy?
Tram track sign where a part of the mesangial cell process is found within the GBM
What are the findings and differential dx on biopsy and Light microscopy?
Crescent formation: anti GBM nephropathy, ANCA vasculitis, post streptococcal glomerulonephritis, IgA nephropathy, lupus nephritis.
Tram track sign: membranoproliferative glomerulonephritis
Thin and split GBM: due to absence of type 4 collagen seen in alport syndrome
What is the difference of causes of nephritic syndrome on immunofluorescence?
Linear: anti GBM
Paucii immune (no immune complex deposition): ANCA vasculitis
Granular appearance:
Lumpy bumpy (subepithelial): PSGN
Subendo and epithelial: lupus nephritis
Immune complex deposition: MPGN 1
C3 dense deposits: MPGN 2
Mesangial deposition: IgA nephropathy
Treating the complications of nephritic syndromes:
Proteinuria: decreased protein intake, ACE inhibitors and ARBS
Edema: fluid and Na restriction, diuretics
Hypertension: Ace inhibitors, ARBS
Treat cause to prevent renal failure:
steroids to improve renal function if it does not then go to plasmapheresis (anti GBM, ANCA vasculitis). If renal function becomes stable with steroids then may need to give some sort of long term immunosuppressant (cyclophosphamide + tacrolimus)
What is the difference between nephritic and nephrotic syndrome pathophysiologicaly?
Nephrotic syndrome is podocyte dysfunction and nephritic syndrome is GBM dysfunction
What is the difference between nephritic and nephrotic syndrome on urinalysis and microscopy?
Nephrotic syndrome would have heavy proteinuria and lipiduria.
Nephritic syndrome has haematuria, sterile pyuria, proteinuria (below nephrotic range, <3.5g\day. Except for lupus nephritis and membranoproliferative glomerulonephritis)
What is the difference between nephritic and nephrotic syndrome on 24hr urine?
Proteinuria is gonna be equal to or greater than 3.5g\day in nephrotic syndrome and less than 3.5g\day in nephritic syndrome except in 2 types
Where is renal dysfunction more common nephrotic or nephritic syndrome?
AKI or CKD is more common in nephritic syndromes due to rapidly progressive glomerulonephritis. There would be decreased GFR, increased BUN creatinine and BP
What differences would you see serologically to differentiate the types of nephritic syndromes?
Goodpastures: haemaptysis and anti GBM antibodies
ANCA Vasculitis: C -ANCA -> GPA
P -ANCA -> MPA and eosinophilia and asthma sx mean EPA
Hereditary nephritis: visual and auditory issues in a child (anterior lenticonus and features of sensory neural deafness)
PSGN: 1-2 wks post strep inf, anti ASO and anti DNASE B antibodies, low C3 levels
LN: ANA and anti DsDNA and low c3. Hx of SLE
MPGN: nephritic factor. Not obvious so may need biopsy to confirm
IgA: normal c3, IgA vasculitis (Henoch Schoenlein purpura leisons, GIT problems like pain or joint pain) 1-2 day post upper resp orGIT inf in history
Which diseases can have a complication of rapidly progressing glomerulonephritis leading to renal failure?
Goodpasture’s syndrome, ANCA vasculitis, post streptococcal glomerulonephritis, IgA nephropathy and Lupus nephritis.
What components of blood do we not want to pass through the GFB?
RBC
WBC
Proteins
What is injured in Nephrotic syndrome?
Podocytes injury mostly affecting protein causing massive protein loss
What is the term given to podocyte injury in Nephrotic syndrome?
Podocyte effacement
What are the characteristics of Nephrotic syndrome?
Proteinuria (equal to or more than 3.5g a day) (frothy urine)
Hypoalbuminemia (decreases in osmotic pressure resulting in oedema) (less than 25g per litre)
Lipiduria\hypercholesterolemia (low albumin causes increased liver production of albumin, LDL and VLDL which are filtered out of the GFB. Also there is a loss of lipoproteins in the proteinuria meaning more free flowing lipids)
RAAS activation: hypertension, Na/H2O retention leading to edema
Edema: peripheral pitting edema, orbital edema (due to Na+ retention or low protein fluid)
Antithrombin III loss: increased clots (increased risk of PE, DVT, renal vein thrombosis) – increased coagulability
Immunoglobulins loss (less antibodies so more likely to get infection especially from Strep Pneumoniae)
What are the primary types of Nephrotic syndromes? Why are the called primary
Minimal change disease (MCD), membranous nephropathy, Focal Segmental Glomerulosclerosis these 3 diseases account for 80% of Nephrotic syndromes
They are called primary as they have idiopathic causes. Though they can be secondary which means they are resulted from something else.
Membranous nephropathy and focal segmental glomerulosclerosis if left untreated can cause major damage resulting in chronic kidney disease.
What are the secondary types of nephrotic syndrome? Why are they secondary?
Diabetic nephropathy and Amyloid nephropathy.
they are seen as secondary as they can only be caused secondary to another disease.
What is the most common cause of nephrotic syndrome in children? In adults?
Children: minimal change disease
Adults: membranous nephropathy, focal segmental glomerulosclerosis
Cause of Nephrotic Syndrome:
read on notes
Which causes of nephrotic syndrome can progress to chronic kidney disease?
Membranous nephropathy
Focal segmental glomerulosclerosis
Diabetic nephropathy
Amyloid nephropathy
Diagnosis of nephrotic syndrome:
- Urinalysis and microscopy:
Nephrotic syndrome would have proteinuria and lipiduria (fat oval bodies)
-24 urine or spot urinalysis (UACR)
Greater than 3.5g per 24hr
Massive albumin loss
-Serum albumin and lipid panel
hypoalbuminemia
hypocholesterolaemia (VLDL LDL triglycerides)
Diagnostic hints for secondary causes of nephrotic syndrome:
Minimal change disease: children, hodgkin’s lymphoma, NSAIDs, infection or recent immunisation
Membranous nephropathy: adult Caucasian, test for HIV, hep, syphilis (rpr), medications (gold, penicillamine)
Focal Segmental glomerulosclerosis: ethnic (black or Hispanic) adult, HIV, heroin use
Diabetic nephropathy: hx of diabetes, HBA1C >7%
Amyloidosis: SPEP\UPEP, fat pad biopsy
Renal biopsy in unclear cause
What is the most common cause of chronic kidney disease?
What is the most common cause of nephrotic syndrome?
Diabetes
Diabetes
What are the characteristics of nephrotic syndrome and its causes on renal biopsy: in light microscopy, electron microscopy and immunofluorescence?
In general Light microscopy shows us general details. EM zooms into podocytes. Immunofluorescence looks for antibodies or immune complexes that have deposited in the glomerulus
MCD (minimal change disease)
LM: normal
EM: podocyte effacement
IF: normal
Membranous nephropapthy
LM: thick GBM
EM: podocyte effacement, immune complex deposition (spike and dome GBM)
IF: granular subepithelial immune complex deposits
FSGS
LM: focal hyalinosis and sclerosis
EM: podocyte effacement
Don’t usually do biopsy for Diabetic or amyloid nephropathy as can usually identify with history. If you want the extra its 1:00:41 onwards on ninjanerd
Treatment of complications of nephrotic syndrome:
PICTURE IN NOTES
Proteinuria: low protein intake, Ace inhibitors, or ARBs (these inhibit RAAS and angiotensin II) .
Hyperlipidemia: diet changes, statins
Edema: Fluid Na+ restriction, diuretics
Hypercoagulable state (antithrombin 3 loss): anticoagulation
Increased infection risk (because loss of immunoglobulins) : more susceptible to infection especially strep pneumonia so pneumococcal vaccination and decrease edema.
How is antithrombin III lost and what does that result in, in nephrotic syndrome?
AT III is an anticoagulant and inhibits factor X and thrombin which stimulate clot formation.
this means the body is in a hypercoagulable state meaning increased risk of DVT, PE and renal vein thrombosis.
Treatment of cause of nephrotic syndrome:
If it is secondary causes then treat the underlying cause eg: MN treat HIV, syphilis etc
Primary cause of nephrotic syndrome:
Start pt on steroids to recude immune response. Good response to steroids is indicative of primary minimal change disease. Poor response is likely to be primary MN and FSGS -> renal biopsy to confirm. Once confirmed give pt long term immunosuppressants such as cyclophosphamide or tacrolimus
