Specific Glomerular Diseases

Question 1

Good definition of Nephritic Syndrome?

Answer 1

Glomerular diseases characterized by glomerular inflammation and bleeding.

Question 2

5 common clinical presentations of nephritic syndrome?

Answer 2

Hematuria, red cell casts in urine, azotemia, oliguria, and mild to moderate hypertension.

Question 3

Define acute proliferative glomerulonephritis and what is the main cause?

Answer 3

Group of diseases characterized by diffuse proliferation of of glomerular cells with infiltration of leukocytes. Typically caused by immune complexes

Question 4

What is the most common exogenous antigen induced complex causing acute proliferative glomerulonephritis?

Answer 4

Post-infection. Most common infection is streptococcal.

Question 5

What type of strep infection and what age group of patient is most common on post infection glomerulonephritis?

Answer 5

Strep of the skin or pharynx. Children 6-10 most common.

Question 6

What is the MOA for post-streptococcal GN?

Answer 6

Immune complexes of strep antigens and antibodies being formed In Situ

Question 7

What are the 3 strains of A-Beta hemolytic Streptococcal that are nephritogenic?

Answer 7

1,4, and 12

Question 8

What do they think is the principal antigen in most post strep GN?

Answer 8

SpeB

Question 9

What is the classic histologic picture of post strep GN and what is the cause of it?

Answer 9

Enlarged, hyper cellular glomeruli because of infiltrating leukocytes and proliferation of the glomerular cells.

Question 10

What two things are shown on immunofluorescence as far as being deposited?

Answer 10

IgG and C3

Question 11

What is the hallmark electron microscopic finding for post strep GN?

Answer 11

Humps, which are the antigen antibody complex at the sub-epithelial surface.

Question 12

What 4 clinical signs do patients present with when they have post strep GN?

Answer 12

Hematuria (coca cola colored urine), mild hypertension, oliguria, and periorbital edema.

Question 13

What is rapidly progressive glomerulonephritis and what is its histological hallmark?

Answer 13

Severe glomerular injury but does not have a specific cause. Histo feature is crescents.

Question 14

What are the three pathogenic mechanisms of RPGN and what is the common demonization in all types?

Answer 14

Antibodies against the GMB, immune complex deposition, and neither, which is usually associated with ANCAs.

Question 15

What syndrome is an example of the Anti GBM mediated pathway and what are the 2 features of the syndrome?

Answer 15

Goodpasture Syndrome. Antibodies attack the basement membrane in the lungs and kidneys leading to bleeding of the lungs and renal failure.

Question 16

Besides the crescents, what are two other common histological features of severe glomerular injury in RPGN?

Answer 16

Fibrin strands between the cell layers in the crescents and ruptures in the GBM.

Question 17

3 clinical presenting symptoms of RPGN?

Answer 17

Severe and fast loss of renal function, severe oliguria, and nephritic syndrome.

Question 18

What is the big picture problem going on in Nephrotic Syndrome?

Answer 18

Problems with glomerular capillary walls resulting in increased permeability to plasma proteins.

Question 19

6 main clinical manifestations of nephrotic syndrome?

Answer 19

Massive protein in the urine, hypoalbumin, generalized edema, hyperlipidemia and lipiduria, hypercoagulable state (due to loss of AT3), and hypoimmunoglobulins (so infections).

Question 20

In children younger than 17 and adults, nephrotic syndrome is caused by what kind of disease/condition?

Answer 20

In children it is cause by a lesion primary to the kidney and in adults it is usually caused by a systemic disease.

Question 21

What are the 3 most common systemic conditions causing nephrotic syndrome?

Answer 21

Diabetes, amyloidosis and SLE.

Question 22

What are the 3 most common/important primary glomerular lesions and what ages do they present in and what races if applicable?

Answer 22

1. Minimal change disease - kids
2. Membranous glomerulopathy - Caucasian adults
3. Focal segmental glomerulosclerosis - Hispanics and African Americans of all ages.

Question 23

How do we characterize Minimal Change Disease?

Answer 23

Effacement of foot processes of visceral epithelial cells and is only detectable by electron microscopy.

Question 24

What are the 3 reasons Minimal Change Disease points to an immunological basis and what is the one thing that this disease does not present with?

Answer 24

1. Associated with respiratory infections
2. Great response to corticosteroids
3. T cell mediated attack
   NO immune complex deposition.

Question 25

What are two clinical features of Minimal change disease?

Answer 25

Selective Proteinuria (mostly albumin) and dramatic response to corticosteroids.

Question 26

How do we characterize membranous nephropathy?

Answer 26

Thickening of the glomerular capillary wall because of deposits containing Ig on the subepithelial side of the basement membrane.

Question 27

What is the primary cause of Membranous nephropathy and when identifiable, what is the cause of it associated with, 4 things?

Answer 27

Usually idiopathic. Drugs (NSAIDS and penicillin), SLE, Malignant tumors (lung and colon), and infections (Hep B and C).

Question 28

What is the hallmark histo feature of Membranous Nephropathy?

Answer 28

Uniform, diffuse Thickening of the glomerular cap wall.

Question 29

What is the hallmark electron Microgram feature of Membranous Nephropathy?

Answer 29

Irregular spikes protruding from the GBM.

Question 30

What do they think is the antigen that antibodies are attacking in MN?

Answer 30

PLA2

Question 31

Primary focal segmental glomerulosclerosis is the most common cause of what?

Answer 31

Nephrotic syndrome in adults in the US

Question 32

What is the primary cause of FSG and what are 3 other conditions it can be associated with outside of its primary cause?

Answer 32

Idiopathic. HIV, heroin use and sickle cell anemia.

Question 33

4 characteristic features of FSG that are different from MCD?

Answer 33

1. Higher incidence of hematuria, reduced GFR and hypertension.
2. Protein in the urine is less selective
3. Poor response to corticosteroid
4. Progression to chronic kidney disease

Question 34

What is the epithelial damage in FSG that is the hallmark damage of the disease?

Answer 34

Damage the visceral epithelium resulting in effacement of the podocytes.

Question 35

Mutations leading to FSG and really any nephrotic syndrome are causing what problems? Think big picture here.

Answer 35

They are screwing up the slit diaphragm and the associated podocytes/foot processes.

Question 36

What are the two most common mutations associated with FSG and probably also with nephrotic syndrome in general? What are the proteins these mutations affect?

Answer 36

NPHS1 (nephron protein) and NPHS2 (podocin protein).

Question 37

2 important morph features of FSG?

Answer 37

Focal and segmental sclerosis of glomeruli. Effacement of foot processes.

Question 38

What is a morphological variant of FSGD the book mentions. Explain what it looks like?

Answer 38

Collapsing glomerulopathy. Collapsing of the glomerular network so the cap lumens are super narrow.

Question 39

This type of lesion, the collapsing of the glomerular network, is the most characteristic lesion of what associated nephropathy?

Answer 39

HIV

Question 40

What is MPGN? What are the two types of MPGN?

Answer 40

MPGN is more a immune mediated injury rather than a disease.
Type 1: immune complexes of IgG and complement depositing
Type 2: more complement depositing than anything.