B/ 72 The Nephrosis syndrome

Question 1

Nephrosis syndrome is characterized by

Answer 1

Massive proteinuria, daily loss of over 3.5g in adults
Hypoalbuminemia
Generalized edema
Hyperlipidemia and lipiduria

Question 2

Chain of events in nephrosis syndrome

Answer 2

Derangement of the capillary wall of the glomeruli leads to an increase in permeability which allows for leakage of proteins into the glomerular filtrate leading to proteinuria.
A longstanding proteinuria leads to hypoalbuminemia which gives a decreased oncotic pressure within the capillaries and allows for generalized edema.
Due to the edema there is less plasma volume, which leads to decreased GFR - activating the renin-angiotensin-aldosterone system which worsens the edema further.
Hypoalbuminemia also leads to a compensatory reaction of the liver where it hyper synthesizes and secretes proteins such as lipoproteins leading to hyperlipidemia and lipidurea.

Question 3

Difference in children and adults

Answer 3

In Children nephrosis syndrome is almost always due to a primary lesion of the kidney, while in the adult it is almost always a secondary manifestation of a systemic disease.

Question 4

Minimal change disease (Lipoid nephrosis) - Etiology

Answer 4

Most common in children. Abnormality is seen only in the electron microscope. Here we can see thinning of the foot processes of the podocytes. Also, the cells of the proximal tubule are often filled with protein and lipids due to reabsorption of the lipoproteins passing through the disease glomeruli. This is what gives the name “Lipoid nephrosis”.

Question 5

Minimal change disease - Pathogenesis

Answer 5

An infectious disease stimulated the T-cells to produce cytokines. These cytokines can cause damage to the foot processes of the podocytes which detaches them from the basement membrane. This leads to the loss of the anionic charge of the filtration barrier, allowing for proteins to leak through.

Question 6

Minimal change disease - clinical course

Answer 6

Reversible disease, corticosteroid therapy

Question 7

Focal segmental glomerulonephritis - etiology

Answer 7

Characterized by sclerosis affection only some glomeruli (thus focal), and only a segment of each affected glomerulus (thus segmental).
The disease is associated with HIV and heroin abuse, a secondary event to other forms of GN, inherited or congenital defects in a certain component of the podocytes, primary disease (20-30% of nephrotic syndrome cases).

Question 8

Focal segmental glomerulonephritis - pathogenesis

Answer 8

Injury to the foot processes leads to increased permeability and leakage of plasma proteins - deposition of hyaline-like material.

Question 9

Focal segmental glomerulonephritis - Morphology

Answer 9

Focal-segmental deposition, initially only the juxtameduallry nephrons are affected, but later all the glomeruli are sclerosed. Global sclerosis along with tubular atrophy and interstitial fibrosis.
Specifically IgM deposits and C3 can be seen in the area of hyalinosis.
With electronmicroscope we can see thinning of the foot processes of podocytes.

Question 10

Focal segmental glomerulonephritis - Clinical course

Answer 10

50% of the individuals progress to chronic renal failure.

Poor response to corticosteroid therapy.

Question 11

Membranous nephropathy (membranous GN) - etiology

Answer 11

Slowly progressive, most common between 30-50 years. Diffuse thickening of the glomerular basement membrane as a response to precipitation and trapping of immune complexes.

Mostly idiopathic, but can occur secondarily to other disorders, such as malaria, syphillis, chronic hep B, malignant lung and colon cancer, SLE

Question 12

Membranous nephropathy - pathogenesis

Answer 12

A form of chronic immune complex nephritis. Idiopathic form is considered autoimmune to an unknown self-antigen.
The reason for the leaky capillaries is immune complexes depositing in the glomeruli. They activate the compliment system which forms MAC leading to activation of mesangial cells and podocytes. They upon stimulation release proteases and oxidants which damage the capillary wall.

Question 13

Stages of development of the thickened basement membrane in membranous nephropathy

Answer 13

1. Deposition of immune complexes - complexes are found in the subepithelial layer separated by spike-like protrusions of glomerular basement membrane ECM. This is called the “spike and dome” pattern.
2. Progression of the disease. The podocytes dislike to lie on the complexes, but rather prefer to lie on the basement membrane. The podocytes solve this by producing a new basement membrane. The immune complexed become embedded in the new GBM.
3. Eventually macrophages remove the immune complexes and thus holes remain.

Question 14

Membrano-proliferative GN -Characterized by

Answer 14

thickening of the basement membrane - even as much as doubling of it. Doubling is due to the splitting of the GBM because of the invasion of mesangial cell foot processes and inflammatory cells. Proliferation of mesangial cells and endothelial cells.

Question 15

Two types of MPGN

Answer 15

Type I MPGN: more common than the other. Caused by subendothelial, electron dense deposits, which are immune complexes.

Type II MPGN: also called “dense deposit disease”. Excessive complement activation due to autoantibodies against C3 converts - which makes it continously active and leads to uncontrolled activation of the alternative complement pathway. Lamina dense and the subendothelial space of GBM look irregular due to the deposition of an unknown material - thus “dense deposits disease”