Pathology of Nephritic Syndrome Flashcards
True or False: in the cortical region of the kidney, by mass, 70% is made up of tubules.
True. The proximal and distal convoluted tubules.
Anything that happens to a glomerulus that impedes blood flow through it (e.g. glomerulonephritis) causes to the tubules downstream. Why?
Because, blood doesn’t properly get to the efferent arteriole to go to supply blood at the peritubular blood supply and vasa recta (ischemia). This is why there can be tubular functional deficits with glomerular disease.
Whats the mesangial matrix?
The extracellular fluid around the mesangium
Albumin is small enough to fit through the foot processes of the podocytes. Why doesn’t it pass?
Albumin is negatively charged and so is the whole podocyte structure. So, the albumin are repelled and cannot pass.
What 2 lab findings go up in azotemia?
BUN and Creatinine
What is the general difference between acute and chronic renal failure?
Acute renal failure has to do with nephrons all being effected by the same disease at the same time while chronic renal failure is usually the loss of single or small groups of nephrons over time until it reaches a critical limit.
What are the 4 morphologic patterns of glomerular disease?
- Cell proliferation
- Mesangial
- Endocapillary
- Epithelial (podocyte) - crescents
- Leukocyte proliferation
- Basement membrane thickening/changes (sometimes only seen in EM)
- Sclerosis (segmental or global)
What is thin basement membrane disease also known as?
benign familial hematuria
Whats the prognosis for thin basement membrane disease aka benign familial hematuria?
Excellent prognosis
It doesn’t lead to anything long term. No ESRD. No death
How common is thin basement membrane disease aka benign familial hematuria?
Occurs in 1% of the population
What causes thin basement membrane disease aka benign familial hematuria?
Mutations in genes encoding collagen IV
What is the issue with thin basement membrane disease?
Nothing serious, really. It just causes hematuria. It often mimicks a disease process and requires biopsy. When it is diagnosed, the patient doesn’t need to be followed or rebiopsied or anything.
What’s Alport’s Disease?
Alport’s disease is a X-linked genetic condition that causes nephritis, deafness, and ocular lesions. It is due to a mutation in the alpha-5 chain of collagen IV which causes a problem in forming basement membranes.
How do you diagnose Alport’s disease?
Basket-weave pattern basement membrane seen on EM
What’s the prognosis for alport’s disease?
Poor. It typically progresses to ESRD
What are the 2 hereditary disorders that mimic true glomerulonephritis?
- Thin Basement Membrane Disease (aka Benign Familial Hematuria)
- Alport’s Disease
What is the hallmark of endocapillary hypercellularity?
Occlusion of capillary loops
What is the hallmark of epithelial (podocyte) hypercellularity?
Crescents (a reaction to severe injury to glomerular capillaries)
What is this?
Mesangial proliferative glomerulonephritis
You can see that the mesangium is hypercellular. There is increased mesangium and increased nuclei. However, the glomeruli are intact.
What’s this?
IgA deposits in the mesangial region for Mesangial proliferative glomerulonephritis
How does IgA nephropathy typically present?
Usually asymptomatic hematuria although there can be nephritic or nephrotic presentation. It often coincides with URI or GI infection and liver disease.
What is treatment and prognosis for IgA nephropathy?
You can try to treat with steroids although response isn’t certain. Some IgA nephropathy progresses to ESRD.
What is Henoch-Schonlein Purpura?
It is a systemic IgA vasculitis due to systemic deposition of IgA immune complexes. It may involve the kidneys, skin, joints, and GI tract. The renal biopsies look like IgA nephropathy.
Henoch-Schonlein Purpura is more likely to occur in what age group?
Kids less than 10 years of age, although it can occur in elderly
True or False: Henoch-Schonlein Purpura often occurs after upper respiratory infections, especially streptococcus, so it can be often confused with post-strep nephropathy.
True
What’s this?
12y/o boy
Sick for 3 weeks w/ strep
Got better then worse.
Lethargic, flu symptoms, no appetite but gained weight
Creatinine 2.5
1+ protein dipstick
RBCs and RBC casts
Acute nephritic syndrome from postinfectious glomerulonephritis.
Hypercellular and no open capillary loops means this is endocapillary proliferation. On the right side is the silver stain which clearly shows the basement membrane and the PMNs.
What is postinfectious glomerulonephritis?
Usually poststreptococcal infections (or other bacterial etiologies are possible) with acute nephritic syndrome.
It is an exogenous immune complex mediated process in strep with an antigen called SpeB which is cationic (or other cationic exotoxins). This makes sense because the glomerulus has a negative overall charge so cationic proteins stick to it.
What does postinfectious glomerulonephritis look like on EM?
Subepithelial hump-like deposits
What does postinfectious glomerulonephritis look like on IF?
Granular GBM (“Starry Sky”)
How do you treat postinfectious glomerulonephritis? What’s the prognosis?
Only supportive therapy.
99% of children recover completely while about 60% of adults recover.
What is the serology finding in postinfectious glomerulonephritis?
Elevated Antistreptolysin O or “ASO” (if it’s from strep)
What’s going on here?
Patient has a rapidly progressive nephritic syndrome
These are crescents in the process of forming. You see cells filling in the bowman’s space with necrosis and fibrinogen.
What is crescentic glomerulonephritis?
It is not a specific disease process–it’s a histologic picture. We see crescents and know there has been severe injury and have to figure out why. The etiology is diverse.
It tends to present as rapidly progressing glomerulonephritis (RPGN) and the number of glomeruli effected correlates with overall prognosis.
What’s the most important step for finding out what is causing crescentic glomerulonephritis?
Immunofluorescence
- Linear staining (BM itself is the antigen)
- Goodpasture’s syndrome
- Anti-GBM
- Granular staining (immune-complex mediated)
- IgA
- SLE
- Endocarditis
- Idiopathic
- No staining “pauci-immune”
- Wegener’s
- Microscopic PAN
- Churg-Strauss
- Idiopathic
What is anti-GBM disease?
It is a rare autoimmune disease where Nephrotoxic IgG antibodies are directed against the alpha-3 chain of collagen IV in the basement membrane of tissues.
If it is renal-limited, it’s called anti-GBM disease.
If it’s renal and lung, it’s called Goodpasture’s syndrome.
What is the classical presentation of anti-GBM disease?
RPGN and hemoptysis
How does Anti-GBM disease appear in immunofluorescence?
Linear
How do you treat crescentic glomerulonephritis?
Steroids, cytotoxics, plasmaphoresis
What is lupus nephritis?
Lupus nephritis is the renal component of the systemic disease prosess (SLE) that happens in about 2/3 of SLE patients. It is an immune complex mediated process w/ ANA and anti-dsDNA
What disease typically shows a “full house” on IF?
Lupus nephritis.
It shows everything. It’s a granular immune-complex pattern with positive IgG, IgA, IgM, C1q, and C3
How does lupus nephritis present?
Unfortunately, it presents however it wants to.
Asymptomatic, nephritic, nephrotic, mixed nephritic-nephrotic, RPGN, whatever.
How is renal lupus classified?
WHO Classification
Class I: No or minimal changes by light microscopy
Class II: Mesangial glomerulitis
Class III: focal, segmental glomerulonephritis
Class IV: diffuse glomerulonephritis *most severe
Class V: membranous nephropathy (class V would be expected to be the most severe because it’s the highest number but it’s not.. it’s just completely different)
What is therapy for lupus nephritis?
Steroids and cytotoxics
What’s the prognosis for lupus nephritis?
Usually good with treatment
