Nephritic Syndrome - Nichols Flashcards
What are the three basic components of nephritic syndrome?
Hematuria
Renal Insufficiency
Hypertension
What are the distinct set of symptoms common to all nephritic syndromes?
Oliguria
Hematuria
Hypertension
Is nephritic syndrome typically acute or chronic?
acute with onset of days, not weeks
In nephritic syndrome, where are the immune complexes frequently deposited?
subendothelial locations,
except for post-infectious glomerulonephritis which tends to be subepithelial
What, in a general pathology sense, can immune complex deposition in subendothelium lead to?
complement activation which leads to cell damage, which can lead to thrombus formation in glomerular capillaries (a complication of nephritic syndromes)
How does the immune complex deposition lead to leukocyte infiltration?
the immune complexes trigger cellular destruction, which releases cytokine and autocoids. This attracts the leukocytes, which enhances inflammation and can cause glomerular capillary rupture, releasing blood into the urinary space
What usually causes post-infectious glomerulonephritis?
an initial case of group A beta-hemolytic streptococci infection, 1-6 weeks after infxn
How does pts present with post-strep glom.?
proteinuria, edema, azotemia, htn, gross hematuria, with smoky urine, oliguria in some cases
What complement pathway does post-strep glom use/
c4 because c3 levels are low. suggesting an alternative pathway
What titers are usually present in post-strep glom/
anti-streptolysin 0 titers, used for dx
What does immunoflu show?
diffuse granular deposits of IgG and C3 in glomerular capillary walls and mesangium. HAve dome-shaped subepithelial deposits reffered to as HUMPS
How do you treat post-strep glom?
mgmt of htn, loop diuretics, and renal replacement therapy when severe
What will you see upon light microscopy of membranoproliferative glomerulonephritis?
increased thickening of the GBM with a proliferation of glomerular cells and infiltration of inflamm cells.
Which of the types of membranoproliferative glom. isn’t actually part of the category?
type II, more details later
What is the characteristic appearance of the gbm in membranoproliferative cells upon silver staining?
tram tracks, because the two gbm membrane (a new one formed in reparative phase)
What percentage of MPGN type I ?
80%
What conditions can lead to mpgn?
hepatitis c and many others, usually secondary in adults and primary in children
Where is mpgn more common now?
south america, africa and middle east
Explain the patho of type 1 mpgn?
mediated by immune complexes causing compl activation by classical pathway. Injury phase with influx of leukocytes leading to proliferative phase, with damage to capillary walls from cytokines and proteases. Endothelial cells lose fenestrations and effacement of podocytes occurs.
reparative changes follow with new basement membrane formation and entrapment of immune complexces and etc leading to the tram track appearance along the capillary walls.
What are the clinical presentations of mpgn 1
hemature (macro or micro)
proteinuria
usually follows an upper respiratory tract infxn
What is the tx and prognosis of mpgn1?
no consensus tx usually leads to esrd
who typically presents with mpgn?
older children and younger adults 7-30
What is dense deposit disease aka?
type II mpgn
What is the typically person with dense deposit disease?
older children and younger adults 7-30
what causes dense deposit disease?
NOT immune-complex mediated but dysregulation of complement activation due to congenital mutations
What abs develop in dense deposit disease
anti- factor h factor I factor B and c3 convertase
what does immunofluo show in dense deposit disease
granual deposits of c3 along gbm and in mesangium. however they are dense and visible, as opposed to mpgn1.
what is the characteristic description of deposits seen in ddd?
ribbon like
Where else can you see ddd?
HOw do you distinguish between ddd and type i mpgn?
in the bruch membrane of the eye, leading to decreased vision. lipodystrophy with loss of subcu fat in upper half of body. abs to c3 convertase
What is IgA nephropathy also known as?
Berger’s disease
What is the characteristic feature of IgA nephropathy?
depositino of polymeric IgA1 in the mesangial matrix.
What are things that lead to secondary IgA nephropathy?
celiac disease, chronic liver disease who have reduced hepatobiliary clearance, also IBS, psoriasis, dermatitis,
what is the typical person with iga neph?
children and young males
What typically triggers iga nephr?
upper respiratory or gi tract infxn
what do you see upon light microscopy in iga neph?
mesangial widening
what does immunofl show in iga neph/
mesangial iga deposits with c3 and properdin
what is the clinical presentation of iga neph?
microscopic hematuria, gross hematuria at times, proteinuria in nephrotic range, acute glomerulonephritis, htn
what do you use to treat iga neph?
steroids, acei, arb
what is considered the systemic form of iga nephropathy?
henoch-schonlein purpura
how often do people with iga “relapse”
every few months
What type of collagen is targeted in Anti-GBM disease?
alpha3, compared to alpha v in alport syndrome
Where is the expression of the antigen that is targeted in Anti-GBM limited to?
the non-collagenous domain of the alpha3 chain of collagen type IV is only expressed in the pulmonary alveolar basement membrane and the gbm
What can trigger the formation of the autoantibodies for alpha3 collagen?
exposure to hydrocarbons, drugs, viruses tumor or (most commonly) smoking
what is the typically person with anti-gbm?
young white males
What can be seen in histology of anti-gbm disease?
crescentic necrotizing gn with linear deposits of IgG along gbm, but not visible by electron microscopy
what do pts with anti-gbm prseent with?
nephritic syndrome, prominent hematuria and quickly ensuing renal failure, azotemia, arthritis and arthralgia
what are signs and symptoms of anti-gbm that involve pulmonary?
dyspnea, cough hemoptysis and crackles, anemia due to pulmonary hemorrhage
what is a subset but really just another name for anti-gbm disease?
goodpasture’s syndrome
how can you treat goodpastures/anti-gbm
plasmapheresis and steroids and immunosuppressive therapy
Is rapidly progressive glomerulonephritis a disease or something that can result from many different disease?
something can result from many different diseases
What are the characteristics of rapidly progressive glomn?
nephritic syndrome, rapid loss of renal fxn, oliguria and if untreated, death in weeks to months.
What is seen histologically in rapidly progressive glmni?
the presence of crescents in bowman’s capsule, composed of proliferating parietal epithelial cells, macrophages, fibrin, and areas of necrosis
Why is the fact that there is proliferation in the bowman’s capsule significant?
to be there, it has spread through the endotherlium, gbm, and through the visceral epithelium
is rapidly progressive glmni ab-mediated or cell-mediated/
can be both
what is the consequence of the crescents?
they visibly compress the tuft of capillaries, impairing or obliterating blood flod into the tuft.
What are examples of linear rapidly progressive glmni?
anti-gbm disease/goodpastures
what are examples of granular (immune complexes) rapidly prog glmni?
primary or secondary renal disease
what are exmaples of rapidly progressie glmni that don’t involve any deposition of immune complexes
anca-associated, drug-induced, idiopathic
What is significant in immunoflu in type II rapidly prog glmni?
lumpy bumpy deposits of IgG in the GBM and mesangium
What diseases show Type II rapi progr glmni?
post-infxs glomermni
iga nephropathy
When do you seen type III pauci rapi prog glmni?
in people with ANCA
p-anca with skin, kidneys, others, aka microscopic polyangiitis
c-anca in wegeners granulomatosis, kidneys lung and upper respiratory tract
What causes alport syndrome?
the result of mutations in genes for one of the alpha chains of the collagen type IV (alpha5).
what do mutations in the alpha5 chain of type iv collagen result in
a defective heterotrime assembly and defective BMs.
where is the collagen heterotrimer in alports syndrome used in the body?
lens, cochlea, and glomeruli
Pts with alport syndrome have problems with what?
nerve deafness, lens disorders and nephritis
How does the gbm appear on light microscopy in alport syndrome?
thin or attenuated. may show several alternating thing lyaers of lamina rara and lamina densa resembling a basket weave
What does the mutation in alpha 5 chain prevent?
the normal fusion of basement membranes, resulting in “basket weave” pattern
how is alports syndrome passed on
x-linked, so males are much more affected than the women with the trait
how are males affected by alport syndrome
persistent hematuria (compared to mild for women), progressive proteinuria and esrd
what is defective in thin basement membrane disease?
alpha3 chain or alpha4 chain in type iv collagen causing uniform reduction in gbm to about half or normal thickness, presenting with persistent microscopic hematuria
what is the typical pt with alport syndrome
5-20 yo
