Glomerular Diseases Flashcards by Katherine E Nordstrom

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)

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How is glomerulonephritis different from glomerulopathy?

both are damage to the glomerulus

glomerulopathy does not have an inflammatory component

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Identify the indicated aspects of the normal glomerular lobe

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What is shown in the provided image?

Electro micrograph of a normal renal glomerulus

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What are the 3 methods for evaluating kidney biopsies?

Electron micrographs
Immunofluorescence
Light microscopy

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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

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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

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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

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Identify the different types of deposits indicated by the numbers:

1, 2, 3 & 4

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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

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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

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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

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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

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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

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What pathology is shown in the provided image?

What demographics are most commonly affected?

Acute Proliferative Glomerulonephritis

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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

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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

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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 are the 3 types of Rapidly Progressive Glomerulonephritis?

Anti-glomerular basemsnet membrane antibody
1. linear IgG & C3 complexes on glomerular basement membrane-
2. also seen in goodpasture syndrome
Immune-mediated complexes
1. Cause: systemic lupus, some medications, chronic hepatitis etc.
Pauci-immune
1. no detectable immune complexes, so immunoflouresence will be negative
2. Will have ANCAs (anti-neutrophil cytoplasmic antibodies) associated with systemic vasculitis

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)

How quickly does Rapidly progressive glomerulonephritis develop?

Symptoms?

Treatment?

Develops over weeks
Symptoms
- server oliguria
Treatment
- intensive plasma phoresis & immunosuppressants

What causes Minimal Change disease?

Most commonly affected demographic?

Symptoms?

Treatment?

Minimal Change Disease

immune dysfunction, elaboration of cytokines that dmage podocytes, damage to peramability barier –> leakiness
- most commmon cause nephrotic syndrome in children
- most commonly occurs after an infection or an immunization, asthma, after some medications & in kids who have lymphoma or leukemia
Symptoms
- usually NO hematuria, hypertension or renal failure
- abrubpt onset nephrotic syndrome
- due to immune dysfunction & cytokines, capillaries get quite leaky (& loss of large amounts of protein)
Treatment
- Steriords- good long-term prognosis

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 is Focal Segmental Glomerulosclerosis? Symptoms? Most commonly affected demographics? Cause?

* A group of "podocytopathies" of varied etiologies share the feature of focal segmental glomerulosclerosis * Symptoms * typically moderate to heavy, nonselective proteinuria * hematuria, renal insufficiency & hypertension * Demographics * MOST common cause of nephrotic syndrome in adults * Cause * primarily idiopathic * also, IVDA, HIV, sickle cell anemia, immune disorders, etc.

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

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 is the cause of chronic glomerulonephritis?

* Results from many different kinds of glomerulonephritis, or may develop without any antecedent history of such * Morphology varies with stage of disease End Stage Renal Disease

What pathology is shown in the provided image?

Trichrome stain showing complete replacement of almost all glomeruli by collagen (blue)

What is another name for IgA Nephropathy? Cause? Demographics affected? Symptoms?

Berger Disease * Deposition of IgA in the mesangium, mesangial proliferation * Demographics * most common type of glomerulonephritis worldwide * more common- southern europe, asia, & in native americans * less common- persons of african descent * 10-29 years * M\>F * Symptoms * recurrent hematuria after respiratory infection * slowly progressive to renal failure in 20-50% * recurs in renal transplants

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 renal diseases are common in individuals with Diabetes Mellitus?

* Nephropathy * end stage renal disease in ~40% * Glomerular disease * proteinuria * Hyalinizing arteriolosclerosis * Tubular lesions * Increased susceptibility to papillary necrosis & pyelonephritis

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)

What are the 6 classes of Systemic Lupus Erythematosus Nephritis? \*\* do not have to memorize

1. **Minimal _mesangial_ lupus nephritis** * immune complex depositionin the mesangium (least common) 2. **_Mesangial_ proliferative lupus nephritis** * deposition of immunoglobulin and complement and mesangial cell proliferation 3. Focal lupus nephritis * involvement of less than 50% of all glomeruli. Segmental or global - variable presentation 4. **Diffuse lupus nephritis** * most _common_ & _severe_ form * involvement of \>50% of all glomeruli- mesangial hypercellularity and crescent formation 5. **Membranous lupus nephritis** * immune complex deposition with thickening of capillary walls (**_subepithelial_**) * morphologically similar to iodpathic membranous GN, usually with nephrotic syndrome 6. **Advanced sclerosing lupus nephritis** * sclerosis of **\>90%** glomeruli with end stage renal disease

The immune complexes involve in systemic lupus erythematosis nephritis include what components?

* IgA * IgG * IgM * C3 * C4 * Kappa & Lambda light chains

Why do patients present as differnet classes with systemic lupus erythematosis nephritis? Clinical presentation?

We do not know & they can switch between classes * Clinical presentation (variable) * hematuria * nephritic syndrome (hypertension) * nephrotic syndrome * rapidly progressing golmerular nephritis