Glomerular Diseases Flashcards
What is Glomerulonephritis?
What are the different types?
inflammation of the glomerulus
- Types:
- diffuse (involves all the glomeruli in the kidney)
- focal (only some of the glomeruli - ie. region)
- global (of the golmeruli involved, the entire glomerulus is effected)
- segmental (will only involve a segment of the golmerulus)
How is glomerulonephritis different from glomerulopathy?
both are damage to the glomerulus
glomerulopathy does not have an inflammatory component
Identify the indicated aspects of the normal glomerular lobe
What is shown in the provided image?
Electro micrograph of a normal renal glomerulus
What are the 3 methods for evaluating kidney biopsies?
- Electron micrographs
- Immunofluorescence
- Light microscopy
Identify the components of the glomerular filter
- Filtration slits (arrows) and diaphragm are situated between the foot processes
- Basement membrane consists of central lamina densa sandwitched between lamina rara interna and lamina rare externa
What are the ways that the glomerulus respond to injury?
-
Hypercellularity
- proliferation of the mesangial cells or endothelial cells
- infiltration of leukocytes (neutorphils, monocytes, macrophages, lymphocytes)
-
proliferation of crescents (proliferation of epithelial cells) & infiltration of leukocytes
- due to damage of the capillary walls (ie. vasculitis, immune mechanisms, infections, toxins, etc. )
-
Basement membrane thickening
- best seen in the PAS (stain) sections b/c basement membrane stains pink & so it shows up nicely
- deposits of different types of cryoglobulins (something else extrinsic) & could be on endothelial or epithelial side
- can get increase in the components of the protein membrane itself - (typically Diabetes Mellitus)
-
Hyalinosis
- accumulation amorphous pink material
- can also be seen as a result of endothelial capillary cell wall injury (also seen in hypertension)
-
Sclerosis
- extracellular collagen matrix that is put down in the mesangium, capillary loops, or both
- Antibody-Mediated
Describe the process of antibody-mediated glomerular injury
- Can have immune complexes formed elsewhere that are found in the circulation, get deposited on the renal glomerulus
- due to physical/chemical charcteristics of the glomerulus
- directed against antigens that get planted in the glomerulus from elsewhere or intrinsic antigens
- Deposition
- basement membrane
- sub-endothelial deposits (inflammation)
- sub-epithelial
- can be deposited
- basemenet membrane protects them somewhat from inflammtory mediators
Identify the different types of deposits indicated by the numbers:
1, 2, 3 & 4
What i the difference between the two images provided
- image on right has more of a granular pattern due to the deposition of discrete antigen/antibody complex
- on right, there is a “linear pattern” that is seen with anti-glomerular basement membrane disease
Describe how the inflammatory response in the golmerulus affects chronic vs. acute problems
- Inflammatory infiltrate
- mostly neutrophils, (some macrophages/monocytes)
- Purpose of the inflammatory response is to break down the immune complexes & get rid of them
- can eventually have resolution of the disease if it is a one-time event (ie. infection)
- Chronic (ie. chronic Hep C or B, systemic lupus erythematosus) w/ ongoing immune complex deposition
- do not have the resolution, it is a chronic, progressive, disease that can lead to end-stage renal disease
What happens in glomerular epithelial cell injury?
- Types of injury in glomerular disease
- Epitheial cell injury - may be the only thing you see
- won’t have significant inflammatory process, no thickening of the basement membrane, just have effacement of foot processes (may only be seen w/ electron microscopy
- toxin or immune reaction can cause damage to the epithelial cell or podocytes
- effacement: flattenign out of the epithelial foot proceses/abnormal morphology & will comporomise the funtion
- can retract & detach & lead to damage of the basement membrane
- Epitheial cell injury - may be the only thing you see
What is shown in the provided images? These features are indicative of what problem?
Major histological features of progressive renal damage
- Focal segmental glomerulosclerosis
- progressive fibrosis involving portions of some glomeruli
- portion that is hyalinized
- Tubulointerstitial Fibrosis
- tubular damage & interstitial inflammation
- worsening fibrosis in this interstitium
Describe the differences in clinical presentation for nephritic & nephrotic syndrom
- Nephritic (left)
- inflammation in glomeruli (can be a result of the immune reaction to an infection)
- Presentation: hematuria, urine RBC casts (left), azotemia, oliguria, and mild/moderate hypertension
- proteinuria is commonm–not in nephrotic range
- Nephrotic (right)
- derangement in glomerular capillary walls, which leads to increased permeability to plasma protei
- protein uria > 3.5 g/day
- hypoalbuminemia –> edema
- hyperlipidemia
- vulnerable to infections and thrombosis
- Lipiduria (cholesterola crystals (L) & refractile bodies (R) in urine
What pathology is shown in the provided image?
What demographics are most commonly affected?
Acute Proliferative Glomerulonephritis
What causes Acute Proliferative Glomerulonephritis?
What demographics are most affected?
Presenting symptoms?
Recovery?
- Cause
- with previous skin infection or pharyngitis (strep)
- sterile lesions due to immune reaction
- Demographics
- mainly a disease in children-
- Symptoms
- abrupt onset fever, malaise, hematuria, & dark urine
- 1-4 weeks after Strep infection
- diffuse & global
- Recovery
- 95% kids will recover quickly
- < 1% will develop progressive renal disease / renal failure
- 60% adults will recover quickly
- 95% kids will recover quickly
What pathology is shown in the provided image?
Acute Proliferative Glomerularnephritis IF stain
- discrete, coursely granular deposits of complememtn C3 corresponding to subepithelial “humps”
- Electron dense supepithelial “hump” (right) appears as dark gray sphere
What pathology is shown in the provided image?
** High yield
Rapidly Progressive Glomerulonephritis Crescents
PAS stain
- Severe glomerular injury that we see with a variety of diseases - typically presens with nephritic syndrom where you have rapid decline in renal function
What pathology is shown in the provided image?
**not as high yield
- Electron microscopy showing characteristic wrinkling of glomerular basement membrane, with focal disruptions (arrows)
What pathology is shown by the provided images?
Minimal Change Disease
- by light microscopy, it looks perfectly normal
- but with electron microscopy, you can see effacment of foot processes (arrows)
- absence of deposits- no antigen/antibody complexes
- no sub-epithelial humps
What comparison is being depicted by the provided images?
Notice the effacement of the foot processes in the Minimal Change Disease
What is Membranous Glomerulonephropathy?
What demographic is most commonly affected?
Symptoms?
- Common cause of nephrotic syndrome in adults
- Most are idiopathic
- Capillary leakiness from compliment activation leads to release of proteases & oxidases
- leads to massive loss of protein
- Symptoms
- insidious onset; indolent (causing little to no pain) course
- thickening of the basement membrane
What pathology is shown in the provided image?
Membranous Nephropathy
- Left
- silver stain showing spike formation along the thickened basement membrane
- b/c spikes with immune-complex deposition
- Right
- Subepithelial deposits are separated by projections of the basement membrane
- deposits are darker & membrane is lighter
How will membranous nephropathy appear via immunoflouresence?
granular appearance
of immune-complex deposits
What pathology is shown in the provided images?
Focal Sclerosing Segmental Glomerulonephritis (FSGS)
Whta is Membranoproliferative Glomerularnephritis?
Cause?
Types?
- Nephrotic syndrome (20% of nephrotic syndromes)
- Cause
- primary- idiopathic
- secondary- autoimmune, cancer, infections (hepB, C, or malaria)
- Types
- I: source of antigens is usually unknown
- subendothelial deposits
- II: dense deposit disease; activation of alternate complement pathway
- C3 nephritic factor present in blood
- intramembranous deposits
- In both, the basement membranes appear split (double-contous) on light microscopy because of interpositionof mainly mesangial cell processes into the basement membrane
- I: source of antigens is usually unknown
What pathology is shown in the provided images?
Membranoproliferative Glomerulonephritis (MPGN)
- Left (notice they are more cellular than they shoudl be)
- Right- regular glomerulus
The provided image is a high power view of the glomerulus.
What pathology is depicted by the image?
Membranoproliferative Glomerulonephritis (MPGN)
Type I
Marked increas in mesangial matrix with peripheral extension of mesangial cells, producing a “tram tack” double contour appearance (capillary walls)
What pathology is shown in the provided images?
** do not have to differentiate on the test
What pathology is shown in the provided image?
Trichrome stain showing complete replacement of almost all glomeruli by collagen (blue)
What pathology is shown in the provided image?
- in ligh microscopy, you can note some proliferation in the mesangium & an increase in the matrix
- Right- stain specifically for IgA in the mesangium
What pathology is shown in the provided image?
Diabetes Mellitus – Diabetic Nephropathy
- Left (also common with hypertension)
- PAS positive deposition in vascular wall; markedly thickened & eosinophilic
- amorphous - does not have normal arteriolar structure
- ** could be confused with amyloidosis (would do a congo red stain to differentiate)
- PAS
- shows thickened renal tubular basement membranes
What pathology is shown in the provided image?
Diabetic Nephropathy
- Left
- thickened basement membrane as shown by electron microscopy
- Right
- diffuse & nodular diabetic glomerulosclerosis
- deposition mesangial matrix & nodular depositions (kimmelstiel wilson nodules)
