Term
| what important factors to take into account when considering renal pathology? |
|
Definition
| clinical symptoms, a particular group of dominance and comorbidities |
|
|
Term
| what are the different levels of renal pathology in terms of etiology? |
|
Definition
| primary (disease originates in glomerulus), secondary (ex: lupus/diabetes), hereditary (5 major glomerular syndromes) |
|
|
Term
| what are some of the more common histologic changes seen in renal disease? |
|
Definition
| basement membrane thickening, hyalinization/sclerosis, and hypercellularity |
|
|
Term
| how does basement membrane thickening occur in the kidney? |
|
Definition
| deposition of amorphous *electron-dense material such as immune complexes on the endothelial or epithelial side of the BM/within the BM itself can lead to a thickening of the BM proper |
|
|
Term
| how does hyalinization and sclerosis occur in the kidney? |
|
Definition
| homogeneous eosinophilic material accumulates, appearing on electron microscopy as an *extracellular hyalin made of *plasma proteins that have extruded from circulating plasma - causing obliteration of the capillary lumina. many forms of glomerular damage may be the end result due to hardening. |
|
|
Term
| how does hypercellularity occur in the kidney? |
|
Definition
| this may appear as "cell packing" on EM due to cellular proliferation of mesangial or endothelial cells may occur, leukocyte (neutrophils, monocytes, and lymphocytes) infiltration may occur, and formation of crescents (*parietal epithelial cells and leukocytes - most likely initiated by *fibrin leakage into the bowman's space) may occur. the more crescents you have - the poorer the prognosis. |
|
|
Term
| what is a common way of classifying various forms of glomerulonephritis? why? |
|
Definition
| many forms of glomerulonephritis have no known cause and are classified based on their histology |
|
|
Term
| what does diffuse glomerular disease usually involve? |
|
Definition
|
|
Term
| what does global glomerular disease usually involve? |
|
Definition
|
|
Term
| what does focal glomerular disease usually involve? |
|
Definition
| only some of the glomeruli |
|
|
Term
| what does segmental glomerular disease usually involve? |
|
Definition
| a part of each glomerulus |
|
|
Term
| what does mesangial glomerular disease usually involve? |
|
Definition
| predominately the mesangial region |
|
|
Term
| what is underlying most forms of primary glomerulonephritis as well as many secondary forms? |
|
Definition
| immune mechanisms - a majority of pts w/glomerular deposits of Ig (often mixed with complement) |
|
|
Term
| can cell-mediated immune reactions play a role in concert with antibody-mediated events? |
|
Definition
|
|
Term
| what are some common kinds/patterns of immune complex deposition? |
|
Definition
| 1) antibodies react directly with intrinsic tissue antigen/antigens planted in the glomerulus from the circulation 2) anti-glomerular BM antibody induced nephritis 3) heyman nephritis |
|
|
Term
| how does anti-glomerular basement membrane (GBM) induced nephritis occur? |
|
Definition
| in this in situ nephritis, antibodies are directed against intrinsic fixed antigens (which are normal components of the GBM and are components of non-collagenous domain (NC1) of collagen type IV), they bind along the *entire length of the GBM - causing a diffuse linear pattern of staining for the antibodies (as opposed to "lumpy bumpy") |
|
|
Term
| what is heymann nephritis? |
|
Definition
| in this in situ nephritis, immune reactants produce numerous *electron dense deposits along the subepithelial aspect of the BM, creating granular immune deposition (lumpy-bumpy) resulting from the reaction of antibody w/antigen complexes on the visceral epithelial cells |
|
|
Term
| what is circulating immune complex nephritis? |
|
Definition
| in this kind of nephritis, complexes of antigen and antibody are formed in circulation and are trapped in the glomeruli (either subepithelial or subendothelially). these antibodies are not specific for glomerular elements, but their trapping nonetheless causes damage |
|
|
Term
| why do complexes localize in the glomerulus in circulating immune complex nephritis? |
|
Definition
| due to physiochemical properties and hemodynamic forces |
|
|
Term
| what kinds of antigens are found in circulating immune complex nephritis? |
|
Definition
| there can be endogenous antigens as in SLE or exogenous ones, like those in streptococcus or hepatitis infections |
|
|
Term
| what do glomerular lesions in circulating immune complex nephritis consist of? |
|
Definition
| leukocytic infiltration (particularly with exogenous infections) along with proliferation of both mesangial and endothelial cells |
|
|
Term
| are molecular charge and size of the reactants important in circulating immune complex nephritis? |
|
Definition
|
|
Term
| how do highly cationic immunogens tend to behave in circulating immune complex nephritis? |
|
Definition
| highly cationic immunogens tend to cross the GBM and are found in the *subepithelial position |
|
|
Term
| how do molecules with a neutral charge tend to behave in circulating immune complex nephritis? |
|
Definition
| molecules with a more neutral charge tend to accumulate in the *mesangium |
|
|
Term
| how do highly anionic immunogens tend to behave in circulating immune complex nephritis? |
|
Definition
| highly anionic immunogens tend to be excluded from the GBM and are trapped subendothelially. they may not be nephritogenic at all. |
|
|
Term
| how might antibodies to glomerular cell antigens cause nephritis? |
|
Definition
| antibodies to glomerular cell antigens may react w/cellular components and cause injury by cytotoxic or other mechanisms |
|
|
Term
| how might antibodies to mesangial cells cause nephritis? |
|
Definition
| antibodies to mesangial cells lead to mesangiolysis and mesangial cell proliferation |
|
|
Term
| how might antibodies to endothelial cell antigens cause nephritis? |
|
Definition
| antibodies to endothelial cell antigens cause endothelial cell injury and thrombosis |
|
|
Term
| how might antibodies to visceral epithelial cells cause nephritis and more commonly nephrotic syndrome? |
|
Definition
|
|
Term
| what is the pattern of immune deposition in most glomerular antibody mediated injury? is it usually clear by what mechanism the deposition occured? |
|
Definition
| in most glomerulonephritis, the pattern of immune deposition is granular and along the GBM or mesangium. it may be difficult to determine if the deposition occured in situ, by circulating complexes - or both |
|
|
Term
| what contributes to the morphologic diversity found in glomerulonephritis? |
|
Definition
| in situ immune reactions, trapping of circulating complexes, and interactions of these two events along with the local hemodynamic and structural elements in the glomerulus |
|
|
Term
| can sensitized T cells cause some forms of glomerular injury? |
|
Definition
| yes, activated macrophages and T cells can be found in the glomerulus and cause injury |
|
|
Term
| how can epithelial cell injury manifest itself in glomerulonephritis? |
|
Definition
| antibodies may be induced to visceral cell antigens, toxins and certain cytokines may all lead to effactment of foot processes, vacuolization, retraction and detachment of cells from the GBM - ultimately causing leakage and subsequent *proteinuria |
|
|
Term
| what are some mediators of glomerular injury? |
|
Definition
| neutrophils, monocytes, macrophages, T cells, NK cells, platelets and resident glomerular cells |
|
|
Term
| how do neutrophils and monocytes cause cell injury in the glomerulus? |
|
Definition
| neutrophils and monocytes can both generate chemotactic agents (C5a), proteases (degrade GBM), oxygen derived free radicals and arachidonic acid metabolites |
|
|
Term
| how do macrophages, T cells and NK cells cause cell injury in the glomerulus? |
|
Definition
| they can release a large number of biologically active molecules |
|
|
Term
| how do platelets cause cell injury in the glomerulus? |
|
Definition
| platelets can aggregate in the glomerulus and release eicosanoids and growth factors |
|
|
Term
| can resident glomerular cells cause injury? |
|
Definition
| yes, they can be stimulated to produce multiple inflammatory mediators |
|
|
Term
| what are the two major histologic characteristics of progressive renal damage? |
|
Definition
| focal segmental glomerulosclerosis (not all glomeruli and not all the parts of the affected glomeruli are affected) and tubulointerstitial fibrosis (often the endpoint) |
|
|
Term
| what usually initiates focal segmental glomerular sclerosis? |
|
Definition
| glomerulosclerosis is initiated by an adaptive change in unaffected glomeruli - such as compensatory hypertrophy |
|
|
Term
| what happens with glomeruli that undergo compensatory hypertropy in focal segmental glomerular sclerosis? |
|
Definition
| they maintain renal function, but proteinuria and glomerulosclerosis soon develop -> leading to uremia |
|
|
Term
| what hemodynamic changes accompany glomeruli that undergo compensatory hypertropy in focal segmental glomerular sclerosis? |
|
Definition
| increased blood flow, filtration and transcapillary pressure |
|
|
Term
| what are the overall consequences of focal segmental glomerular sclerosis? |
|
Definition
| endothelial and epithelial cell injury, proliferation of mesangial cells, increased protein permeability (eventually proteinuria develops - even if the primary disease was nonglomerular), and accumulation in the matrix - all leading to macrophage infiltration, ECM accumulation, significant sclerosis (with a *significant reduction in renal mass* over time) = widespread kidney disease |
|
|
Term
| does focal glomerulosclerosis exacerbate or result from reductions in renal mass? |
|
Definition
| it can do both - cyclical problem, common end product to many pathologies |
|
|
Term
| other than focal segmental glomerular sclerosis, what is the other broad categorization of renal damage? |
|
Definition
| tubulointerstitial fibrosis - affecting the tubules rather than the glomeruli, duh |
|
|
Term
| what is tubulointerstitial fibrosis a component of? |
|
Definition
| this form of tubular damage and interstitial inflammation is a component of acute and chronic glomerulonephritis - and contributes to the progression of immune and nonimmune glomerular diseases |
|
|
Term
| what are factors that contribute to tubulointerstitial fibrosis? |
|
Definition
| *ischemia of tubule segments downstream from sclerotic glomeruli, acute/chronic *inflammation in the interstitium, damage/loss of *peritubular capillary blood supply, *direct damage from proteinuria, and *activated tubular cells elaborating proinflammatory cytokines/chemokines/growth factors (contribute to fibrosis) |
|
|
Term
| which cytokines are illiciting the inflammation associated with tubulointerstitial fibrosis? what about the actual fibrosis? |
|
Definition
| inflammation: IL-1, TNF-alpha, and INF gamma. fibrosis: PDGF, TGF beta1, ET-1 |
|
|
Term
| what are the primary glomerular diseases? |
|
Definition
| acute diffuse proliferative glomerulonephritis (poststreptococcal/non-poststreptococcal), rapidly progressive glomerulonephritis (cresentric), membranous glomerulonephropathy, minimal change disease, FSGS, membranoproliferative glomerulonephritis, IgA nephropathy, and chronic glomerulonephritis |
|
|
Term
| what are systemic diseases with secondary glomerular diseases? |
|
Definition
| SLE, DM, amyloidosis, goodpasture syndrome, microscopic polyarteritis/polyangitis, wegener granulomatosis, henoch-schonlein purpura, and bacterial endocarditis (many vascular diseases - kidneys are vascular organs) |
|
|
Term
| what are some inherited glomerular disorders? |
|
Definition
| *alport syndrome, fabry disease, and thin basement membrane disease |
|
|
Term
| what are the primary forms of pathology in the nephritic syndromes? |
|
Definition
| acute postinfectious glomerulonephritis (what will give you a primarily nephritic picture), rapidly progressive glomerulonephritis (anti-GBM nephritis), and IgA nephropathy |
|
|
Term
| what is the most common cause of acute postinfectious glomerulonephritis? are there regional differences? |
|
Definition
| beta hemolytic streptococci. in northern latitudes, acute postinfectious glomerulonephritis is commonly associated with respiratory strep infections, in southern latitudes, acute postinfectious glomerulonephritis is commonly associated with skin infections |
|
|
Term
| who is acute postinfectious glomerulonephritis usually seen in? when does it occur? |
|
Definition
| usually children, but not always. acute postinfectious glomerulonephritis usually will occur a few weeks (1-4) after recovery from the strep infection |
|
|
Term
| what needs to be taken into account taking the hx of a pt you suspect may have acute postinfectious glomerulonephritis? |
|
Definition
| blood/protein in the urine, periorbital edema, recent hx of strep throat or skin infection, and HTN or renal insufficiency |
|
|
Term
| is acute postinfectious glomerulonephritis usually nephritic or nephrotic in terms of its clinical picture? |
|
Definition
| nephritic, characterized by hematuria. this can be accompanied by some proteinuria, edema, HTN and renal insuffciency |
|
|
Term
| what are lab findings associated with acute postinfectious glomerulonephritis? |
|
Definition
| serum complement *C3 levels are *low and anti-streptolysin O titers are usually elevated |
|
|
Term
| what mediates acute postinfectious glomerulonephritis? |
|
Definition
| acute postinfectious glomerulonephritis is an antibody mediated disease with circulating or planted antigens |
|
|
Term
| what is observed in acute postinfectious glomerulonephritis via light microscopy? |
|
Definition
| hypercellularity with prominent *neutrophilic infiltration (not a common finding in other glomerulonephritis - makes sense w/bacterial aspect). there may be some partial *obliteration of the lumen due to proliferation of endocapillary cells and crescent formation is rare. |
|
|
Term
| what is seen with acute postinfectious glomerulonephritis using immunoflorescence? |
|
Definition
| *IgG and *C3 are deposited (serum C3 is decreased, but it is still deposited in the peripheral and mesangial portions of the glomerulus) |
|
|
Term
| what is seen in acute postinfectious glomerulonephritis via EM? |
|
Definition
| immune deposits are typically found in subepithelial locations - lumpy bumpy |
|
|
Term
| what is taken in to account when considering the prognosis for acute postinfectious glomerulonephritis? |
|
Definition
| the age of the pt and whether the infection is sporadic or epidemic -children with epidemic cases tend to have complete recovery (few children develop RPGN or chronic renal failure). adults however in 15-50% of cases progress to irreversible renal damage (greater likelihood than kids) |
|
|
Term
| what is rapidly progressive glomerulonephritis? |
|
Definition
| RPGN is a rapid progressive loss of renal function w/severe oliguria and death from renal failure w/in weeks to months |
|
|
Term
| is RPGN nephritic or nephrotic? |
|
Definition
| mainly nephritic, characterized by proteinuria, hematuria, azotemia, and anemia (nephrotic also seen, but less common) |
|
|
Term
| are crescents seen with RPGN? |
|
Definition
| yes, crescents or accumulation of fibrin and cells in bowman's spaces are present, and the higher their level - the worse the prognosis |
|
|
Term
| what is RPGN type I associated with? |
|
Definition
| RPGN type I is associated with *anti-GBM antibodies (includes *goodpasture syndrome - lungs may also be involved, definitely consider if pts present with hemoptysis and hematuria) and idiopathic RPGN |
|
|
Term
| what is RPGN type II associated with? |
|
Definition
| RPGN type II is associated with *secondary glomerular immune complex pathology that includes idiopathic, postinfectious, SLE, and henoch-schonlein purpura |
|
|
Term
| what is RPGN type III associated with? |
|
Definition
| pauci immune and ANCA-associated |
|
|
Term
| what is the distribution of anti-GBM glomerulonephritis? |
|
Definition
| bi-modal, it can peak at 2 different age groups: middle aged and elderly |
|
|
Term
| what is a common presentation associated with anti-GBM glomerulonephritis? how does it present clinically, on LM? |
|
Definition
| goodpasture syndrome (autoimmune disease triggered when the patient’s immune system attacks goodpasture antigen (type II hypersensitivity), which is found in the kidney and lung). with goodpastures, glomerulonephritis is seen, along with pulmonary hemorrhage, and hemoptysis. on *LM, necrotizing glomerulonephritis is seen w/*crescents (often in over 50% of glomeruli - compressing and impairing function) |
|
|
Term
| what is seen on immunoflourescence w/anti-GBM glomerulonephritis? |
|
Definition
| generalized diffuse depositis of IgG and C3 - which may be *linear granular |
|
|
Term
| what is seen on EM w/anti-GBM glomerulonephritis? where are the antibodies seen to bind specifically w/goodpastures? |
|
Definition
| *sub-endothelial deposits (lumpy bumpy). in goodpastures, the auto-antibodies bind to the non-collagenous domain of collagen IV found in the basement membrane (specifically the *alpha 3 chain) |
|
|
Term
|
Definition
| IgA nephropathy, aka berger's disease is recurrent gross or microscopic hematuria with or without proteinuria |
|
|
Term
| who is IgA nephropathy most common in? when? |
|
Definition
| young adult males, often following a URI, UTI, or GI tract infection |
|
|
Term
| is serum IgA increased in IgA nephropathy? what about serum complement levels? |
|
Definition
| yes - in about 50% of cases. serum complement levels are typically minimal (as opposed to post-infectious type) |
|
|
Term
| what is the most common primary glomerulonephropathy *worldwide? |
|
Definition
| IgA nephropathy (aka berger's disease - not beUrger's or thromboangiitis obliterans, associated with smoking) - not necessarily the most common in the US |
|
|
Term
| what is the specific presentation associated with henoch-schonlein purpura? |
|
Definition
| skin rashes, abdominal manifestations, arthralgias, *palpable purpura in the lower extremities*, and renal abnormalities - leading to gross and microscopif hematuria (appears as coke or pepsi) and proteinuria |
|
|
Term
| what might henoch-schonlein purpura progress to? is there a type of Ig associated with it? |
|
Definition
| henoch-schonlein purpura may progress to RPGN (end result) and is associated with IgA - however is different from IgA nephropathy in that it presents with *systemic manifestations* |
|
|
Term
| who is henoch-schonlein purpura seen in commonly? does it often follow another disease? |
|
Definition
| children 3-8 yrs old - usually following a URI (upper resp infection) |
|
|
Term
| is henoch-schonlein purpura more associated with nephritic or nephrotic sydromes? |
|
Definition
| henoch-schonlein purpura can be associated with both nephritic and nephrotic syndrome or some combination thereof |
|
|
Term
| what is the pathology of IgA (bergers - which affects only the kidney) and henoch-schonlein purpura (systemic as well as kidney affected) in terms of LM, immunofluorescence and EM views? |
|
Definition
| via LM: there is *widening of the mesangial area and either *diffuse cellularity or *crescents. immunofluorescence: mesangial deposits of IgA and C3 (occasionally IgG/IgM). EM: electron dense deposits in the *mesangium, *subepithelial and *subendothelial deposits can occur |
|
|
Term
| what is the rate of progression for IgA in terms of eventual renal failure? |
|
Definition
| IgA progresses slowly, about 50% develop end-stage renal failure within 25 years of dx |
|
|
Term
| what is the prognosis for children with henoch-schonlein purpura? |
|
Definition
| most children with henoch-schonlein purpura recover completely, while some adults develop progressive renal failure |
|
|
Term
| what kind of renal disease does SLE result in? |
|
Definition
|
|
Term
| who does SLE most commonly affect? what systems does it affect? how are common presentations? |
|
Definition
| young women and african americans. it affects multiple systems. pts can present with skin rashes (butterfly shape on face), arthralgias, arthritis, inflamed serosal surfaces, renal and CNS involvement |
|
|
Term
| what is the pathogenesis of SLE in the kidneys? what is characteristic of its affects on the kidney? |
|
Definition
| SLE results from deposition of anti-DNA complexes in the glomeruli, characteristically as diffuse proliferative *subendothelial deposits during the acute stages of SLE. 50% of cases have granular deposits of Ig and complement, which may lead to diffuse interstitial fibrosis around the tubules with release of inflammatory cytokines/reactions. |
|
|
Term
| what characterizes the WHO SLE class I? |
|
Definition
| no proteinuria, glomeruli are typically normal, there are no signficant changes seen via LM/EM/immunoflourescence (IF), and renal function tests are good |
|
|
Term
| what characterizes the WHO SLE class II? |
|
Definition
| this is known as mesangial glomerulonephritis. there are no clinical renal abnormalities or minimal proteinura/hematuria. LM: mild/absent mesangial widening or hypercellularity IF: IgC, C3, sometimes IgA/IgM staining in mesangial regions (full house IF) EM: electron dense deposits in *mesangial regions |
|
|
Term
| what characterizes the WHO SLE class III? |
|
Definition
| this is referred to as focal and segmental glomerulonephritis (more severe clinically). 20% of pts are azotemic, most have proteinuria, 20% present with nephrotic syndrome, and 50% have hematuria |
|
|
Term
| how does WHO SLE class III/focal and segmental glomerulonephritis appear on EM, LM, and IF? |
|
Definition
| LM: *segmental proliferation of some glomerular tufts, some necrosis, *karyorrhexis (nuclei begin to break up in large clumps of chromatin), and *focal interstitial inflammation/*tubular atrophy can occur. IF: granular deposition, IgG/C3. EM: subepithelial and subendothelial electron dense deposits |
|
|
Term
| what characterizes the WHO SLE class IV? |
|
Definition
| this is referred to as diffuse proliferative glomerulonephritis and is accompanied by increased impairment of renal function, most pts will be azotemic and hematuria and almost all will have proteinuria - and the majority of these pts will have enough proteinuria to be considered int the nephrotic syndrome range |
|
|
Term
| how does WHO SLE class IV/diffuse proliferative glomerulonephritis appear on LM, IF, and EM? |
|
Definition
| LM: 50% of the glomeruli are involved, crescents are often present, as are tubular changes and necrotizing vasculitis. IF: diffuse granular staining, IgM, IgG, and C3. EM: deposits in all areas of the glomerulus |
|
|
Term
| what characterizes the WHO SLE class V? |
|
Definition
| this is known as membranous glomerulonephritis. most have proteinuria and nephrotic syndrome as well as possibly hematuria and HTN. |
|
|
Term
| how does WHO class V SLE/membranous glomerulonephritis appear via IF, and EM? |
|
Definition
| EM: diffuse and uniform thickening of the glomerular capillary wall by numerous subepithelial deposits (DOMES) with protrusions of GBM material (SPIKES) between subepithelial deposits. mesangial deposits are present, there are *no crescents, there are subendothelial deposits referred to as "wire loop lesions". IF: IgG, C3, sometimes IgM in fine granular deposits outlining capillary walls |
|
|
Term
| what is the prognosis for pts w/SLE-induced renal lesions? what is the tx? |
|
Definition
| the incidence of severe life-threatening renal disease has declined. pts w/classes II and V have excellent prognosis. pts with classes III and IV have a more guarded prognosis. tx is corticosteroids and immunosuppressive agents |
|
|
Term
| what is alport's syndrome? who is more commonly affected? |
|
Definition
| a hereditary nephritis associated with nerve deafness, lens dislocation, cataracts, and corneal dystrophy. males are more commonly affected and are more likely to progress to renal failure. |
|
|
Term
| how does alport's present clinically in terms of the renal effects? |
|
Definition
| gross and microscopic hematuria as well as RBC casts |
|
|
Term
| when do symptoms of alports start? |
|
Definition
|
|
Term
| what are the genetics of alport's? |
|
Definition
|
|
Term
| what is the pathogenesis of alport's syndrome? |
|
Definition
| defective GBM synthesis, COL4A3, COL4A4, COL4A5 mutations which are components of type IV collagen, and in pts with the X linked disease, there is a mutation in the gene encoding the alpha 5 chain of collagen IV |
|
|
Term
| how does alport's syndrome appear via LM? |
|
Definition
| the glomeruli are always involved, there is thinning of GBM, focal proliferation/sclerosis or both, an increase in the mesangial matrix and infiltration of tubular epithelial cells with *neutral fat and *polysaccaride, glomerulosclerosis, vascular narrowing, tubular atrophy and interstitial fibrosis |
|
|
Term
| in alport's, does the GBM stain with anti-GBM antibodeis via IF? |
|
Definition
|
|
Term
| how does alport's syndrome appear via EM? |
|
Definition
| the basement membrane has irregular foci of thickening or attenuation w/splitting of the GBM |
|
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