Nephrology: Nephritic and Nephrotic Syndromes

Question 1

What are the 3 components of the Glomerular Filtration Barrier?

Answer 1

1. Fenestrated capillaries – controls blood flow
2. Glomerular basement membrane – proteins that make this up are negatively charged to repel large plasma proteins such as albumin and globulins
3. Podocytes – have filtration slits to allow certain molecules to permeate

Question 2

What molecules does GFB block the passage of?

Answer 2

RBC WBC Protein

Question 3

What is damaged in Nephritic syndrome?

Answer 3

Glomerular basement membrane damage causing a leakage of RBC, WBC and proteins (sub nephrotic range)

Question 4

What is the difference in proteinuria between nephritic and nephrotic syndrome?

Answer 4

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)

Question 5

What are the characteristics of Nephritic Syndrome?

Answer 5

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

Question 6

What type of edema is caused by nephritic syndrome?

Answer 6

Mild edema, periorbital or generalise. Would be less than nephrotic

Question 7

What is sterile pyuria?

Answer 7

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

Question 8

What are RBC casts? What are acanthocytes?

Answer 8

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

Question 9

In nephritic syndrome you get a lot of WBC, proteins, and cytokines in the Bowman’s space. What is the complication of this?

Answer 9

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.

Question 10

What are the complications of low GFR?

Answer 10

Oliguria, increased BUN, creatinine in blood causing azotemia and uremia.

Activates RAAS causing hypertension

Question 11

Causes of Nephritic syndrome?

Answer 11

Review on notes its a lot

Question 12

What diseases can have nephritic syndrome with nephrotic range proteinuria?

Answer 12

Lupus nephritis and membranoproliferative glomerulonephritis

Question 13

What is the difference between type 1 and 2 membrane-proliferative glomerulonephritis?

Answer 13

Type 1 doesn’t have any specific antibody that is deposited while in type 2 it is specific antibody which is nephritic factor

Question 14

What is the sign of MPGN on biopsy?

Answer 14

Tram track sign where a part of the mesangial cell process is found within the GBM

Question 15

What are the findings and differential dx on biopsy and Light microscopy?

Answer 15

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

Question 16

What is the difference of causes of nephritic syndrome on immunofluorescence?

Answer 16

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

Question 17

Treating the complications of nephritic syndromes:

Answer 17

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)

Question 18

What is the difference between nephritic and nephrotic syndrome pathophysiologicaly?

Answer 18

Nephrotic syndrome is podocyte dysfunction and nephritic syndrome is GBM dysfunction

Question 19

What is the difference between nephritic and nephrotic syndrome on urinalysis and microscopy?

Answer 19

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)

Question 20

What is the difference between nephritic and nephrotic syndrome on 24hr urine?

Answer 20

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

Question 21

Where is renal dysfunction more common nephrotic or nephritic syndrome?

Answer 21

AKI or CKD is more common in nephritic syndromes due to rapidly progressive glomerulonephritis. There would be decreased GFR, increased BUN creatinine and BP

Question 22

What differences would you see serologically to differentiate the types of nephritic syndromes?

Answer 22

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

Question 23

Which diseases can have a complication of rapidly progressing glomerulonephritis leading to renal failure?

Answer 23

Goodpasture’s syndrome, ANCA vasculitis, post streptococcal glomerulonephritis, IgA nephropathy and Lupus nephritis.

Question 24

What components of blood do we not want to pass through the GFB?

Answer 24

RBC
WBC
Proteins

Question 25

What is injured in Nephrotic syndrome?

Answer 25

Podocytes injury mostly affecting protein causing massive protein loss

Question 26

What is the term given to podocyte injury in Nephrotic syndrome?

Answer 26

Podocyte effacement

Question 27

What are the characteristics of Nephrotic syndrome?

Answer 27

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)

Question 28

What are the primary types of Nephrotic syndromes? Why are the called primary

Answer 28

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.

Question 29

What are the secondary types of nephrotic syndrome? Why are they secondary?

Answer 29

Diabetic nephropathy and Amyloid nephropathy. they are seen as secondary as they can only be caused secondary to another disease.

Question 30

What is the most common cause of nephrotic syndrome in children? In adults?

Answer 30

Children: minimal change disease Adults: membranous nephropathy, focal segmental glomerulosclerosis

Question 31

Cause of Nephrotic Syndrome:

Answer 31

read on notes

Question 32

Which causes of nephrotic syndrome can progress to chronic kidney disease?

Answer 32

Membranous nephropathy Focal segmental glomerulosclerosis Diabetic nephropathy Amyloid nephropathy

Question 33

Diagnosis of nephrotic syndrome:

Answer 33

- 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)

Question 34

Diagnostic hints for secondary causes of nephrotic syndrome:

Answer 34

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

Question 35

What is the most common cause of chronic kidney disease? What is the most common cause of nephrotic syndrome?

Answer 35

Diabetes Diabetes

Question 36

What are the characteristics of nephrotic syndrome and its causes on renal biopsy: in light microscopy, electron microscopy and immunofluorescence?

Answer 36

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

Question 37

Treatment of complications of nephrotic syndrome:

Answer 37

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.

Question 38

How is antithrombin III lost and what does that result in, in nephrotic syndrome?

Answer 38

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.

Question 39

Treatment of cause of nephrotic syndrome:

Answer 39

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