Renal Glomerulonephritis

Front 1

Describe the clinical presentation of the nephrotic syndrome

Back 1

-Heavy proteinuria
-Low serum albumin
-Edema
-High serum lipids

Front 2

Describe the clinical presentation of nephritis/nephritic syndrome

Back 2

-Renal failure
-Hypertension
-Hematuria
-Acute
-Chronic
-Rapidly progressive

Front 3

What are the three categories of renal parenchymal disease?

Back 3

-Nephritis syndrome
-Nephrotic syndrome
-Asymptomatic urinary abnormalities

Front 4

Describe asymptomatic urinary abnormalities

Back 4

A patient will present with isolated hematuria of glomerular origin or proteinuria

Front 5

Describe the results of urine analysis in a patient with nephritic syndrome

Back 5

-Urinary RBCs, sometimes deformed
-RBC casts
-Large amounts of albuminuria (>3g/day)

Front 6

What are RBC casts?

Back 6

RBC casts are outlines of red cells with tubules and protein matrix. If you see these you are usually dealing with a glomerular disease.

Front 7

Describe why the glomerulus is vulnerable to immune complex injury

Back 7

1. Receives 20-25% of CO
2. High glomerular capillary pressure
3. Fenestrated endothelium
4. Concentration (sieving effect)

Front 8

What are the mechanisms of immunologic injury to the glomerulus?

Back 8

1. Glomerular deposition of circulating Ag-Ab complexes. The antigen-antibody complexes can get trapped in the glomerulus because of charge interactions, size, and affinity for the capillary walls.
2. Binding of circulating Ab to fixed glomerular Ag (ie, anti-GBM Ab)
3. In situ immune complex formation. In situ immune complex formation is either due to an antigen being produced by the visceral epithelial cell or because it gets planted first and then antibody binds.

Front 9

Describe the appearance under immunofluorescence with glomerular deposition of circulating Ag-Ab complexes

Back 9

Granular appearance

Front 10

Describe the appearance under immunofluorescence with in situ immune complex formation

Back 10

Granular appearance

Front 11

Describe the appearance under immunofluorescence with binding of circulating Ab to fixed glomerular Ag (ie anti-GBM Ab)

Back 11

Linear

Front 12

How does antigen-antibody deposition lead to disease?

Back 12

-Antigen-antibody complexes form in the glomerular capillary wall
-There is activation of complement through the classical pathway
-C3a and C5a are produced which are chemotaxins and attract neutrophils and sometimes monocytes to the glomerular capillary lumen
-Leukocytes undergo respiratory burst, releasing ROS, lysosomes, and proteases
-This causes damage to the capillary wall and leads to a proliferative response
-Hagemen factors activates leading to the formation of fibrin, plasmin, and kinins
-Platelets come in to plug these areas and release factors that cause mesangial proliferation
-This can lead to glomerulonephritis and eventually glomerulosclerosis

Front 13

Describe the different types of glomerular proliferation

Back 13

-Proliferation of the mesangium (mildest form)

-Endocapillary-proliferation in the glomerular capillary lumen which occludes the lumen. These areboth mesangial and endothelial cells. The indigenous cells of glomerulus as well as infiltrating leukocytes that cause all the hypercellularity in the glomerular tuft.

-Extracapillary (cresentic)-(most severe) The proliferating cells are the cells that normally line Bowman's capsule - the parietal epithelial cells. Sometimes there are some infiltrating leukocytes. This is synonymous with the syndrome of rapidly progressing glomerulonephritis.

Front 14

Describe the different patterns of proliferation of sclerosis

Back 14

-Focal (<50% of glomeruli) vs Diffuse (>50% of glomeruli)
-Segmental (Part of the glomerulus) vs Global (The whole glomerulus)

Front 15

Describe the significance of red cell casts or deformed red cells in urine

Back 15

Indicates glomerular disease

Front 16

Describe urine in proteinemia

Back 16

Bubbly

Front 17

Describe urine in hematuria

Back 17

Coca-cola, Tea colored

Front 18

Describe the presentation of acute nephritic syndrome

Back 18

-Decreased GFR
-Oliguria
-Edema
-Hypertension
-Active urine sediment

Front 19

Describe Post-streptococcal glomerulonephritis/acute post infectious glomerulonephritis

Back 19

-Usually follows pharyngitis but can also follow impetigo
-Involves the glomuli quite uniformly (diffuse)
-Glomeruli are extremely hypercellular
-Endocapillary proliferation present
-Leukocytes infiltrate

Front 20

Describe how Post-streptococcal glomerulonephritis/acute post infectious glomerulonephritis leads to decreased GFR

Back 20

All the leukocyte infiltrate reduced GFR. The more and more capillary loops that are occluded by cell proliferation the lower the creatinine clearance

Front 21

What antigen is responsible for the humps in post-streptococcal glomerulunephritis?

Back 21

Pyrogenic exotoxin B

Front 22

Describe the disruption of the glomerular basement membrane from leukocytes

Back 22

-As the leukocytes come in they release their proteases and ROS
-These can rupture the glomerular basement membrane
-These ruptures allow RBCs to enter the urinary space
-Certain proteins such as albumin solidify blocks of RBCs in the tubuls and lead to red cell cast formation

Front 23

Describe the outcomes of Post-streptococcal glomerulonephritis/acute post infectious glomerulonephritis

Back 23

-In most patients the glomerular architecture is restored
-In some patients (<3%) the glomerular nephritis does not resolve in 6 weeks. If these patients excerise hard or develop a fever they can become symptomatic. This can eventually lead to renal failure
-In some patients (<1%) the immune response is so exuberant that they develop endocapillary and extracapillary proliferaction (crescents). These have a rapidly progressive course leading to renal failure over a period of weeks

Front 24

Describe the etiology of post-streptococcal glomerulunephritis

Back 24

-Follows infection with certain "nephritogenic" streptococcal strains (pharyngitic, dermal, etc)
-More common in children than adults
-Time lag from infection to onset of GN (~2 weeks)
-Nephritic picture common (oliguria, edema, hypertension, active urinary sediment, a rise in BUN and creatinine)
-Low complement and C3
-Positive serologic tests for recept strep infection

Front 25

Describe the prognosis of post-streptococcal GN

Back 25

-Excellent in children
-Good in adults

Front 26

In what diseases are there low levels of serum complement

Back 26

-Acute post-infectious GN
-Lupus nephritis
-Idiopathic MPGN
-Cryoglobulinemic GN

Front 27

Back 27

-Urinary sediment with normal RBCs
-Could come from anywhere - urethra, bladder, ureters, pelvis of the kidney
-Can be from stones, tumor, stricture, or urinary infection

Front 28

Back 28

-Red cell casts
-Indicative of glomerulunephritis
-Red cells are packed together in the shape of the tubule

Front 29

Back 29

-Deformed red cells
-Indicative of glomerulonephritis
-The red cells deform because they are passing through the medulla - a hypertonic and acidic environment

Front 30

Back 30

-Post streptococcal GN/acute post infectious GN
-Usually follows pharyngitis but can also follow impetigo
-Involves glomeruli diffusely
-Glomeruli are hypercellular

Front 31

Back 31

-Post-streptococcal GN/acute post infectious GN
-Usually follows pharyngitis or impetigo
-Endocapillary proliferation
-Endothelial cells and mesangial cells proliferate within the confines of the glomerular basement membrane
-Leukocyte infiltrate present due to release of C3a and C5a

Front 32

Back 32

-Post streptococcal GN/Acute post infectious GN
-Cells are responding to deposits/immune complexes
-Deposits are in red
-Some are large enough to be seen on LM

Front 33

Back 33

-EM of post streptococcal GN/acute postinfectious GN
-Classic hump shaped deposits of post infectious GN
-They are large and sit on the outer aspect of the glomerular basement membrane

Front 34

Back 34

-EM of post streptococcal GN/acute postinfectious GN
-Proteinuria occurs through here because the overlying foot processes are effaced
-Different than membranous glomerulopathy because there are no intervening spikes and these deposits tend to be larger and fewer in number

Front 35

Back 35

-Immunofluorescence of post streptococcal GN/acute postinfectious GN
-Granular pattern of IgG and C3 corresponding to the humps

Front 36

Back 36

-EM of Post streptococcal GN/acute postinfectious GN
-Rupture of glomerular basement membrane from proteases and ROS from leukocytes

Front 37

Back 37

-EM of Post streptococcal GN/acute postinfectious GN
-Ruptured glomerular basement membrane
-Through these rupture sites RBCs can enter the urinary space where they normally couldnt

Front 38

Back 38

-Flea bitten kidney
-The red dots are all red cell casts
-In acute nephritic syndrome the kidney is often swollen

Front 39

Describe the pathogenesis of post-streptococcal GN/acute postinfectious GN in the animal model

Back 39

-Foreign antigen enters
-Over a period of days antigen-antibody complexes form
-Once these reach a critical level complement activates
-Production of a critical level of antigen-antibody complex leads to deposition of circulating immune complexes within the glomerular capillary walls leading to nephritis-Usually self limited and resolves when antigen is depleted
-Response depends on immune response (too weak and not enough complexes, too strong and complexes are too big)

Front 40

Back 40

-EM of Post streptococcal GN/acute postinfectious GN
-Shows the fate of humps over time
-They become more electron lucent and begin to resolve

Front 41

Back 41

-Restoration of glomerular capillary after post streptococcal GN

Front 42

Back 42

-Rare outcome of post streptococcal GN/acute postinfectious GN
-Immune response so exuberant that there is endocapillary and extracapillary (Crescent) proliferation
-Can rapidly progress to renal failure in a matter of weeks

Front 43

Back 43

-Rare outcome of post streptococcal GN/acute postinfectious GN
-End stage renal failure in a patient that never recovered
-We can see that the glomeruli have gone onto sclerosis. They have become acellular balls of matrix material. These are functionally dead glomeruli.
-We have atrophy of the dependent portions of the nephron with tubular atrophy and interstitial fibrosis.

Front 44

Back 44

-Kidney with chronic glomerulonephritis
-Kidney is contracted
-Granular leather grain appearance

Front 45

Back 45

-Kidney with chronic glomerulonephritis
-The granular appearance is because we have many glomeruli in the areas of depression that have gone onto sclerosis.
-Those nephrons have undergone irreversible atrophy and obsolescence.
-There are a few nephrons that are still filtering and these undergo a compensatory hypertrophy. You see these large tubules.

Front 46

Back 46

-Chronic glomerulonephritis kidney cut in cross section
-The cortex is normally 1.2-1.5cm in thickness is not atrophies because so many of the nephrons have become scarred.

Front 47

Back 47

1) Flea-bitten kidney
2) Lipoid nephrosis kidney
3) End stage kidney
4) Normal kidney

Front 48

Back 48

-Heart valve in a patient with endocarditis
-Can lead to post infectious GN

Front 49

Back 49

-Post infectious GN from endocarditis
-Glomerular proliferation is more segmental in distribution
-Same pathogenesis