2. Renal Path 1 Flashcards
Most glomerular diseases are immunologically mediated whereas tubular and what disorders are frequently caused by toxic or infectious agents?
Tubular and interestitial disorders
What is a biochemical abnormality that refers to an elevation of blood urea nitrogen (BUN) and creatining levels, and is related largely to a decreased glomerular filtratation rate (GFR)?
Azotemia
Azotemia is a typical feature of both acute and chronic kidney injury. What type of azotemia is encountered when there is hypoperfusion of the kidneys that impairs renal function in the absence of parenchymal damage?
Pre-renal azotemia
What type of azotemia is seen whenever urine flow is obstructed distal to the kidney, with the relief of obstruction correcting the azotemia?
Post-renal azotemia
Azotemia leads to what, which is characterized not only by failure of renal excretory function (azotemia) but also by metabolic and endocrine alterations resulting from renal damage with secondary involvements of GI system, peripheral nerves and the heart?
Uremia (=azotemia + clinical signs and symptoms)
What syndrome is a clinical entity caused by glomerular disease and is dominated by the acute onset of grossly visible hematuria or microscopic hematuria with dysmorphic red cells and casts on urinalysis, diminished GFR, MILD to MOD proteinuria and HTN?
Nephritic Syndrome (i)
Nephritic Syndrome is the classic presentation of acute poststreptococcal glomerulonephritis. Rapidly progressive glomerulonephritis is characterized as nephritic syndrome withrapid decline in?
GFR
What syndrome is due to glomerular disease and characerized by heavy (more than 3.5G/day) proteinuria, hypoalbuminemia, severe edema, hyperlipidemia and lipiduria?
Nephrotic Syndrome (o)
What kidney injury is chracterized by rapid decline in GFR (hours to days) with concurrent dysregulation of fluid/electrolytes and retention of metabolic waste products normally excreted by the kidney including urea and creatinine? reversible
Acute kidney injury - severe can see oliguria or anuria (no urine)
What kidney disease is defined as presence of diminished GFR that is persistently less than 60mL/min for at least 3 months from any cause, and/or persistent albuminuria, sometimes clinically silent? irreversible
Chornic kidney disease- end result of all chronic renal parenchymal diseases
What occurs when the GFR is less than 5% of normal and is the terminal stage of uremia?
End stage renal disease (ESRD)
Renal tubular defects are dominated by polyuria, nocturia, and electrolyte disorders (metabolic acidosis). They are the result of diseases that directly affect tubular structures or cause defects in?
specific tuburlar functions
What is manifested by spasms of severe pain (renal colic) and hematuria, often with reccurent stone formation?
Nephrolithiasis
11% of the US older adults have chronic kidney dz, it is usually the end result of many renal diseases but most commonly what two factors are the major cause of death from renal disease?
Hypertension
Diabetes
Disorders in which the kidney is the only or predominant organ involved constitute the various types of primary glomerulonephritis/glomerulopathy, all other causes are termed?
Secondary glomerular diseases (SLE, hypertension, diabetes, amyloidosis)
Glomerulus consists of anastomosing of capillaries that are lined by what type of endothelium invested in two layers of epithelial cells?
Fenestrated endothelium
The visceral epithelial cells aka as what, are incorporated into and become intrinsic part of the capillary wall, separated from endothelial cells by a basement membrane?
Podocytes/Foot processes
What type of epithelium sits on the bowman capsule and lines the urinary space, the cavity in which the plasma filtrate first collects?
Parietal epithelium
The average size of the kidney is between 120-150 gms, average length is 10-12 centimeters, and the width is 6cm and thickness is ?
3cm
The kidneys are located retroperitoneally, and the right is lower than the left kidney due to the liver, they sit at about T12 and what is between the lower border of the 12th rib and lateral border of the erector spinae muscle?
renal angle (renal colic pain starts from this angle down and forwards into groin)
On electrophoresis, Gamma, Beta, and Alpha globulin will not travel as far as what, which is the smallest, most negatively charged serum protein (migrates fast)?
Albumin
The entire glomerular tuft is supported by what cells inbetween the capillaries, forming a meshwork with basement membrane, they are contractile, phagocytic and capable or proliferation, laying down matrix and collagen, and secreting biologically active mediators?
Mesangial cells
What is important for the maintenance of glomerular barrier function, which has slit diaphragm presents a size selective distal diffusion barrier to the filtration of proteins and it is the cell type that is largely responsible for synthesis of GBM components (glomerular basement membrane)?
Visceral epithelial cells (podocytes/foot processes)
*NOTE: loss of these are the key event in development of proteinuria
What bridges the filtration slit between two podocyte foot processes, making a slit diaphragm?
Nephrin Molecules
Diabetes is the MCC of ESRD while HTN is the second MCC. In diabetes, primarily it is associated with glomerular disease (microvasculature manifestations = NO tubulointerstitial features), however in systemic HTN it is primarily vascular dz (arteriolar) thus including?
tubulointerstitial dz
What is the normal glomerular filtration rate which decreases with age?
about 100mL/min
All of the following are more characteristic of what renal disease? Nephritic syndrome nephrotic syndrome asymptomatic hematuria or proteinuria chronic renal failure renal tubular defects acute renal failure
Glomerular dz
All of the following are more characteristic of what renal disease? UTI urinary tract obstruction renal tumors nephrolithiasis
Tubulointerstitial dz
All of the following are more characteristic of what renal disease?
Renal tuburlar defects
acute renal failure
BOTH - have characteristics of glomerular and tubulointerstitial diseases
Some inflammatory diseases of the glomerulus are characterized by an increase in the number of cells in the glomerular tuft, known as ? (pathologic response to GM inj)
hypercellularity
Where can the macula densa be found, and what does it consist of?
Found near the afferent arteriole, and contains juxtaglomerular granular cells = make EPO/Renin
Hypercellularity can be d/t proliferation of mesangial/endothelial cells, infiltration of leukocytes, and d/t formation of what, which are accumulations of cells composed of proliferating glomerular epithelial cells and infiltrating leukocytes following an immune/ inflammatory injury involving the capillary walls?
Formation of crescents
Another pathologic response to GM injury is what, which can be seen on LM thickening of cap wall with PAS staining, and on EM you can see deposition of material, increased synthesis of protein components, and formation of additional layers?
Basement membrane thickening
Two other pathologic changes due to injury of the GM is hyalinosis which is accumulation of pink homogenous material (usually end result of glomerular damage) and what, which is characterized by deposition of ECM collagen?
Sclerosis (beyond fibrosis -scarring)
Histologic changes seen in glomerulopathies can be subdivided by distribution, define each of the following. Diffuse Global Focal Segmental
Diffuse: involves all gomeruli
Global: involves entire individual glomeruli
Focal: involves fraction of glomeruli
Segmental: involves part of an individual glomeruli
What mechanisms underlie most forms of primary glomerulopathy and many of the secondary glomerular disorders?
Immune mechanisms
There are two types of immune mechanisms causing glomerular injury, one being abs reacting in situ within the glomerulus and they other GM injury via circulation?
immune complex deposition
What type of nephropathy is associated with injury by antibodies reacting with intrinsic tissue antigen or planted antigens in the glomerulus (major cause of glomerulonephritis)?
Membranous Nephropathy (classic example - nephrotic syndrome - proteinuria)
In membranous nephropathy (in situ immune complex formation), antibody binding to PLA2R in the glomerular epithelial cell membrane forms characteristic deposits of immune complexes along the?
subepithelial aspect of the basement membrane
The pattern seen in IF of membranous nephropathy is known as what rather than being linear as seen in goodpasture anti-GBM?
granular on immunofluoresence
On light microscopy what can be seen in membranous nephropathy ?
thickened basement membrane (hence the name)
Membranous nephropathy develops in some infants fed cow’s milk, have abs to bovine albumin and lesions contain bovine milk antigens, this is a case of abs reacting in situ with what?
planted antigens (such as the milk ags)
What disease is characterized by anti-GBM antibody induced glomerulonephritis, antibodies bind to intrinsic antigens homogeneously distributed along the entire length of the GBM, resulting in a diffuse LINEAR pattern of staining for the antibodies by IF technique?
Goodpasture Syndrome (abs against normal components of GBM)
Goodpasture often occurs in lungs and kidney and is rare, and attacks the noncollagenous part of type IV collagen, causing severe necrotizing and crescentic glomerular damage presenting with?
Hemoptysis / Pulmonary hemmorrhage
Note: auto antibodies on IF show linear pattern of deposition while immune complexes show a?
granular pattern of deposition
Circulating immune complexes get trapped in the GM and cause glomerulonephritis. The antigens trigger the formation of circulating immune complexes from a endogenous origin such as SLE or in IgA nephropathy or they may be exogenous as seen in glomerulonephritis following?
certain infections (mainly viral, some strep)
Whatever the antigen may be, antigen-antibody complexes formed or deposited in the glomeruli may elicit a local?
inflammatory reaction that produces injury
Localization of immune complexes is a key determinant of the injury response and histological features. Immune complexes in the subendothelial portions of capillaries and mesangial regions are accessible to circulation and are more likely to be involved in inflammatory processes that require interaction and activation of circulating?
leukocytes
Disease with immune complexes confined to the subepithelial locations and for which the capillary basement membranes may be a barrier to interation with circulation leukocytes (such as membranous nephropathy) there is typically no?
inflammatory pahology
Note: cationic ag-ab complexes cross GBM and stay in subepithelial areas
anionic ag-ab do NOT cross GBM and are trapped subendothelially = not nephritogenic and neutral charged molecules accumulate in?
mesangium
Podocyte injury is common to many forms of primary and secondary glomerular diseases, stereotypic morphological changes in the podocytes include effacement of foot processes, vacuolization, and retraction and detachment of cells from the GBM causing?
Proteinuria
Loss of podocytes which have only a very limited capacity for replication and repair, may be a feature of multiple types of glomerular injury including focal and segmental glomerulosclerosis and?
diabetic neuropathy (causes proteinuria*)
Once any renal disease destroys functioning nephrons and reduces the GFR to 30-50% of normal, progression to what proceeds at a steady rate, independent of the originial stimulus or activity of the underlying disease?
end stage renal disease (failure) ESRD
The two major histologic characteristics of such progressive renal damage are focal segmental glomerulosclerosis FSGS and ?
tubulointerstitial fibrosis
What is a progressive fibrosis involving portions of some glomeruli developing after many types of renal injury and leads to proteinuria and increasing functional impairment? (*most common cause of nephritic syndrome in adults)
Focal segmental glomerulosclerosis (FSGS)
in Focal segmental glomerulosclerosis (FSGS) there is progressive fibrosis leading to functional impairment, causing proteinuria and hematuria, stems from loss of renal mass and is a result of what changes?
Adaptive changes
Loss of renal mass in Focal segmental glomerulosclerosis (FSGS) results in hypertrophy of the remaining glomeruli (compensation). Podocytes cannot grow in the glomeruli-losing filtration barrier and resulting ultimately in?
Glomerular HTN (assoc w systemic HTN)
This cycle mentioned above in Focal segmental glomerulosclerosis (FSGS) repeats continuously and can be treated with ?
Renin Angiotensin System Inhibitors
Proteins and cells are allowed to leak out in Focal segmental glomerulosclerosis (FSGS), resulting in macrophage induced fibrosis, causing a reduction in?
renal mass
What is tubulointerstitial injury manifested by tubular damage and interstitial inflammation, is a component of many acute and chronic glomerulonephritides?
Tubulointerstitial Fibrosis
Tubulointerstitial Fibrosis is fibroris and inflammation of the tubules and interesitium as opposed to glomerulus, with a stronger correlation between the decline of renal function and the amount of?
tubulointerstial fibrosis (than the severity of glomerular injury)
Tubulointerstitial Fibrosis results from infarction of tubules from alteration of hemodynamics (FSGS), and activation of tubule cells and DIRECT injury from proteinuria or other cytokines. Activated tubule cells express adhesion molecules and elute inflammatory cells leading to?
fibrosis (proteinuria d/t FSGS causes this!)
Glomerular diseases presenting with what type of syndrome are often characterized by inflammation in the glomeruli?
Nephritic Syndrome
Nephritic Syndrome patient usually presents with hematuria, red cell casts in urine, azotemia, oliguria and mild to moderate?
Hypertension
Typically, Nephritic Syndrome is characteristic of acute proliferative and exudative glomerulonephritis and is an important component of?
crescentic glomerulonephritis
What type of glomerulonephritis is a cluster of diseases characterized histologically by diffuse proliferation of glomerular cells (hypercellularity) associated with influx of leukocytes (exudation of), lesions typically caused by immune complexes?
Acute (diffuse) proliferative glomerulonephritis
Acute (diffuse) proliferative glomerulonephritis typically poststreptococcal/postinfectious), with the most common underlying infection being?
Group A beta hemolytic strep
Poststreptococcal gomerulonephritis (GN) is the most common Acute (diffuse) proliferative glomerulonephritis, which appears 1-4 weeks after step infection of the pharynx/skin and is most frequent in children aged?
6-10 (but children and adults may be affected too)
Poststreptococcal gomerulonephritis (GN) is caused by immune complexes containing streptococcal antigens and specific abs formed in situ. Which exotoxin of strep is the principle antigenic determinant in most poststreptococcal GN?
SpeB = streptococcal pyogenic exotoxin B
SpeB = streptococcal pyogenic exotoxin B can directly activate complement and has been localized to what type of deposits of immune complex as characteristic for the dz?
subepithelial hump like deposits
Along with subepithelial hump deposits in poststrep GN, there can also be neutrophils in the GM. Is the proliferation and leukocyte infiltration typically global or diffuse?
BOTH = involving all lobules of all glomeruli
Upon immunofluoresence of poststrep GN, one can see granular deposits of IgG, C3, and sometimes IgM in the msangium and along?
the GBM = corresponding to subepithelial humps!
The immune response to acutre proliferative GN is a nephritic syndrome. Children often present with malaise, fever, nausea, oliguria, and hematuria 1-2 weeks after a?
sore throat (nephritic) - good prognosis
periorbital edema, mild/mod HTN
Adults with poststrep GN are more atypical and aggresive course, may exhibit sudden HTN, edema and frequently have an elevated?
BUN
Child with poststrep GN clear in 6-8 weeks with no renal bx, 95% recover with conservative therapy. In adults only 60% recover completely while there is a higher percent that?
progresses to rapidly progessive GN, or chronic glomerulonephritis
PostINFECTIOUS (nonstreptococcal) acute proliferative glomerulonephritis can happen from OTHER infections than Strep A, such as bacterial, viral (Hep B/C), varicella, or even a sequel to?
parasitic infection
postinfectious acute GN due to staphylococcal infections differs by sometime producing immune deposits containing what Ig instead of IgG **?
IgA
Patients presenting with what syndrome have flomerular inflammatory manifestations leading to hematurial/decreased GFR, typically seen in postinfectious and exudative GN?
Nephritic Syndrome
What type of GN is a syndrome associated with severe glomerular injury and crescent formation in most GM but does not denote a specific etiologic form a GN?
Rapidly Progressive GN (RPGN)
Rapidly Progressive GN (RPGN) is characterized by rapid and progressive loss of renal function, severe oliguria and signs/sx of nephritic sydrome and will lead to renal failure in weeks to months if not treated. What is the most common histologic feature?
presence of crescents in most of the glomeruli (crescentic glomerulonephritis)
*produced by proliferation of parietal epithelial cells lining bowmans capsule and by infiltration of monocytes/macrophages
Rapidly Progressive GN (RPGN) causes collapsed compacted glomerular tufts, crescent shaped masses, obliteration of urinary space and infiltrates of?
monocytes and leukocytes
On EM of Rapidly Progressive GN (RPGN), one can see characteristic wrinkling/tearing of the glomerular basement membrane GBM, and what else?
fragmentation/rupture of the membrane
Rapidly Progressive GN (RPGN) is divided into 3 subdivisions all based on different immunologically mediated glomerular injury.. One is known as type 1 RPGN?
Anti-GNM antibodies that cross react with BM in lungs and renal (Goodpasture)
type 1 RPGN is characterized by linear deposits of IgG and sometimes C3 in the GBM. Goodpasture antigen is within noncollagenous regions of type IV colllagen, associated with a high prevelance of HLA subtypes such as?
HLA-DRB1
To remove pathogenic circulating antibodies associated with type 1 RPGN (goodpasture), one must perform what, which tends to be effective in conjuction with immunosuppressive therapy?
Plasmapheresis
Of the three types of RPGN, 50% of primary renal diseases associated with RPGN have which type of pattern on IF?
Type 3 (pauci immune)
Type 2 RPGN are dzs caused by immune complex deposition as postinfectious, SLE, IgA nephropathy or Henolch-Schloen. Cellular proliferation within glomerular tuft and crescent formation, and in all cases- IF will show what pattern?
Granular pattern of staining chracteristic of immune COMPLEX deposition
*no response to plasmapheresis
Type 3 RPGN are pauci immune- not associated with anti-ab or immune complexes but rather with ANCA (circulating antineutrophil cytoplasmic antibodies), seen in granulomatosis with polyangitis, or microscopic polyangitis, what is diagnostic?
ANCAs!
no pattern upon IF
In RPGN, the kidneys are pale and enlarged, often with petechial hemorrhages on the cortical surfaces. Segmental glomerular necrosis adjacent to GM segments uninvolved are most typically seen in what type?
Type 3 pauci immune
Fibrin strands along with what are prominent between the cellular layers in the crescents in RPGN, which escape into bowmans capsule?
procoagulant factors
The renal manifestions of RPGN (crescentic GN) include hematuria with red blood cell casts in urine, moderate proteinuria, HTN and edema- which are all characteristic of what syndrome?
Nephritic
Nephrotic Syndrome is a derangement of glomerular capillaries with increased permeability to protein with resultant SEVERE?
Proteinuria
Nephrotic syndrome has massive proteinuria (>3.5grams/24hrs), hypoalbuminemia (all is being lost via urine), generalized edema (periorbital initially-due to dec oncotic pressure), and what?
hyperlipidemia and lipiduria (liver compensating for loss of proteins = increasing lipoproteins and cholesterol)
The main causes of nephrotic syndrome are membranous glomerulopathy, minimal change disease, focal segmental glomerulonephritis, what is the most common in children and adults?
Children: Minimal change dz
Adults: Focal semental glomerulosclerosis
The normal urinary protein excretion in adults is less than 150mg/24hours, so 20fold increase of protein loss in nephrotic syndrome which is due to diffuse change in the majority of glomeruli, what is extremely or porous to proteins?
The basement membrane *usually doesnt allow RBC out
Nephrotic patients are vulerable to infections with staph and pneumococcal especially, due to loss of Ig in the urine.What is a common complication due to loss of endogenous anticoagulants in the urine?
thrombotic and thomboembolic complications
Is membranous nephropathy more common in children or adults?
more common in adults while minimal change dz is more common in children under 17
If you are a child under the age of 17, it is most likely a primary nephrotic syndrome, if you are an adult it is probably due to?
systemic disease (SLE, DM, amyloidosis)
What glomerulopathy/nephropathy is characterized by diffuse thickening of the flomerular capillary wall due to the accumulation of depoits containing Ig along the subepithelial side of the basement membrane?
Membranous Nephropathy/Gomerulopathy
Membranous Nephropathy is 75% primary (idiopathic) which is considered to be an autoimmune dz linked to certain HLA alleles such as HLA-DQA1 and caused in most cases by antibodies to the renal autoantigen PLA2 receptor (MC endogenous) with involvement of complement and?
IgG4***
exogenous antigens from Hep B/Treponema
Secondary causes of Membranous Nephropathy include drug classes, malignancies, SLE, infections and other autoimmune dz. Usually presents with nephrotic syndrome (hematuria and HTN in 15-35%) proteinuria is nonselective and does not respond to?
corticosteroids
in Membranous Nephropathy, nonselective means higher molecular weight porteins are found in addition to albumin, can progress to renal failure after 10-40 years and what circulation abs may be a useful biomarker of disease activity?
PLA2 antibodies
On LM one can see uniform diffuse thickening of basement membrane and capillary loops without increase in cellularity, on silver stain, one can see the BM forming what?
spikes into the deposit on the subepithelial side
in Membranous Nephropathy, there will be effaced (obliterated) foot processes, thick BMs, and subepithelial deposits with dense aggregates of?
IgG4
on immunoflueoresence IF, one can see characteristic granular what?
lumpy-bumpy IgG deposits along the glomerular basement membrane
in Membranous Nephropathy, 60% have persistent proteinuria, 40% of them develop renal insufficiency, 10% progress to?
EDSD/failure
What is a relatively benign disorder characterized by diffuse effacement of foot processes of visceral epithelial cells, detectable only be EM, in glomeruli that appear virtually normal by LM?
Minimal Change Disease (MCD)
Minimal Change Disease (MCD) presents with edema and on biopsy you can see FPF only (foot process fusion). The peak incidence is in children between 2-6, and is the MCC of NS in children and may follow a respiratory?
infection or immunization
Minimal Change Disease (MCD) has a immunologic basis, and in certain cases it has been associated with Hodgkin lymphoma, Hypertension is rare and there is proteinuria which is?
HIGHLY selective (mainly albumin)
a characteristic and even diagnostic feature of Minimal Change Disease (MCD) is what?
there is a dramatic response to corticosteroid therapy, >90% respond to therapy with cure
*very good prognosis
the principal lesion in Minimal Change Disease (MCD) is in the visceral epithlial cells which show a uniform and diffuse ?
effacement of the foot processes
Note: only when normal on LM
the cells of the proximal tubules are often laden with lipid and protein, reflecting tubular reabsorption of lipoproteins passing through diseased glomeruli aka ?
lipoid nephrosis
Antibodies against epithelial cell antigens, toxins, cyotkines, or other factors can cause injury resulting in foot process fusion which can be associated with detachment of epithelial cells and protein leakage through ?
defective GBM and filtration slits
What disease is sclerosis of some but not all glomeruli affecting only part of each affected glomeruli with nephrotic syndrome; MCC of NS in adults in the us especially Blacks/hispanics*?
Focal Segmental glomerulosclerosis FSGS
Focal Segmental glomerulosclerosis FSGS has many classifications, including primary (idiopathic), associated with HIV/heroin, as a secondary event reflecting scarring of previously active necrotizing lesions (like in IgA nephropathy), due to adaptive response to loss of renal mass, and uncommonly seen in?
inherited forms/mutations in genes that encode proteins localized to podocyte slit diaphragms
Focal Segmental glomerulosclerosis FSGS accounts for 35% primary kidney in adults and 10% in children, more common in adults in US in hispanics and AA, 20% of patients follow an unusually rapid coure with massive proteinuria and what within 2 years?
renal failure
Focal Segmental glomerulosclerosis FSGS clinical presentation differs from minimal change disease in certain aspects (4)
1. higher incidence of hematuria and HTN
2. Reduced GFR with poor response to CS*
3. significant progression to chronic kidney disease w 50% developing ESRD in 10 yrs
4.
Proteinuria tends to be nonselective (large proteins and small proteins seen in urine)
Focal Segmental glomerulosclerosis FSGS is possibly a progression from MCD with similar effacement of podocytes but with extra epithelial damage and what under LM?
focal segmental sclerosis
Focal Segmental glomerulosclerosis FSGS is associated with many mutations including nephrin (NPHS1), Podocin (NPHS2 (AR)), Alpha-actinin 4 (AD), TRP6, apolipoprotein L1, which ALL localize to the slit diaphragms and?
adjacent podocyte cytoskeletal structures
in Focal Segmental glomerulosclerosis FSGS, in the sclerotic sements, there is collapse of capillaries, and deposition causing hyalinosis, and also commonly seen on LM is.?
lipid droplets/vacuoles (foam cells)
What is a morphological variant of FSGS which is characterized by retraction or collapse of the entire glomerular tuft, with or without additional ‘normal’ FSGS lesions, seen with proliferation and hypertrophy of glomerular visceral epithelial cells?
Collapsing glomerulopathy (worse prognosis)
What is a severe form of collapsing FSGS that is commonly seen in HIV infection, which can directly or indirectly cause renal dz including acute renal failure and or acute interstitial nephritis?
HIV associated nephropathy (more AA than whites)
HIV associated nephropathy is seen in 5-10% of HIV patients and morphologically are seen with a high requency of collapsing FSGS, focal cystic dilation of tubule segments, and lots of tubuloreticular inclusions within endothelial cells that are modifications of?
the ER in the cells by circulating IFN-a
What glomerulonephritis is best considered a pattern of immmune mediated injury rather than a specific disease, with two types?
Membranoproliferative Glomerulonephritis (MPGN)
What type of Membranoproliferative Glomerulonephritis (MPGN) is characterized by the deposition of IgG and complement, tends to be MIXED nephri/otic, occurs in children?
Type 1
What type of Membranoproliferative Glomerulonephritis (MPGN) is known as dense deposit, with the most important aspect being alternative complement activation- C3?
Type 2
Membranoproliferative Glomerulonephritis (MPGN) causes 10-20% in children and its most frequent presentation is combined?
hematuria and proteinuria
Membranoproliferative Glomerulonephritis (MPGN) histologically presents with alterations in the GBM, proliferation of glomerular cells (mesangial/cap loops), leukocyte infiltration and the presence of deposits in mesangial regions and in?
glomerular capillary walls
mesangiocapillary glomerulonephritis
In type 1 MPGN there is evidence of immune complexes in the glomerulus and activation of both classical and alternative complement pathways, most cases in children with a common presentation being?
nephrotic syndrome, HTN, hematuria = MIXED
MPGN has large and hypercellular glomeruli, hypercellularity is produced by proliferation of the mesangium and endocapillary proliferation, along with an increased?
mesangial matrix
The GBM is thickened in MPGN and shows double contour or tram track appearance evident on PAS, this is caused by duplication or SPLITTING of the BM usually as the result of new?
BM synthesis in response to subendothelial deposits of immune complex
In type 1 MPGN morphology, there is characteristic discrete subendothelial electron dense deposits, on IF what can be seen deposited in a granular pattern? 2
IgG/C3
With MPGN you may also see accentuation of lobular architecture, swelling of cells lining peripheral capillaries and an influx of?
NEUTROPHILS (leukocytes)
type 1 MPGN (primary- MIXED) are mainly seen in children, dz follows a slow progressive but unremitting course, with 50% developing?
chronic renal failure in 10 years
Secondary type 1 MPGN is more common in *adults and rises in the following settings: chronic antigenemia (infxn, immune dz, neoplasia), Hep C with cryglobulinemia, Chornic immune complex disorders such as SLE endocarditis, however the outcome is the same as?
type 1 primary = 50% chronic renal failure
What is another name for Type II MPGN, which have abnormalities resulting in excessive activation of the alternative complement pathway?
Dense deposit disease
If Type II MPGN occurs it is a primary renal disease in children (no secondary form). Type 2 is not as common as type 1, Hematuria is a more dominant feature as opposed to what in type 1?
as opposed to proteinuria which is more type 1 (Type 2 is Nephritic Syndrome)
Type II MPGN have generally a severe renal disease and poorer prognosis than type 1, there is a frequent recurrence of MGPN 2 following renal transplant supportin the role of what?
circulating factors
There is a wider spectrum of histologic alterations in dense deposit such as permeation of lamina densa of GBM by ribbon like homogeneous electron dense material, with C3 and properdin seen on IF in the BM but not within?
the dense deposits *IgG absent
Dense deposit-type 2 MPGN is associated with dysregulation of the alternative complement pathway, C3NeF (nephrotic factor) takes place of properdin (binds C3 convertase), enhancing C3 activation and consumption, causing?
Hypocomplementemia
What kidney dz is characterized by the presence of prominent IgA deposits in the mesangial regions and recurrent hematuria*, is the most common type of glomerulonephritis world wide?
IgA Nephropathy (Berger disease)
IgA Nephropathy (Berger disease) is characterized by deposition of IgA in the mesangium on IF (how make dx), and on LM you can see mesangial matrix increase along with?
mesangial cellular proliferation
There are two disease associated with IgA nephropathy, berger which is renal not systemic and what disease, which is an IgA nephropathy associated with systemic dz, seen in purpuric skin lesions and abdominal viscera?
Henoch-Schonlein purpura HSP
IgA Nephropathy histologically varies, but mesangial proliferation/widening, capillary proliferation or overt crescenteric glomerulonephritis may occur. Dx based on IF stains for IgA in granular mesangial patter and will also see what? (3)
IgG
IgM
C3*
IgA Nephropathy presents mainly in older kids young adults, with GROSS hematuria following an infection of the respiratory or?
GI tract (MC)
30-40% of patients will have microscopic hematuria without proteinuria in IgA Nephropathy, but it is important to remember?
recurrent hematuria and bright red blood in urine
What dz is the end point of all nephrotic and nephritic syndromes- end stage for glomerular disease that may result from specific types of glomerulonephritis or may develop without antecedent history or any of the well recognized forms of acute glomerulonephritis?
Chronic Glomerulonephritis (CGN)
in Chronic Glomerulonephritis (CGN), the kidneys are symmetrically contracted and have granular cortical surfaces, the cortex is thinned, and eventually there is obliteration of glomeruli transforming them into acellular eosinophilic masses- presenting a combo of trapped plasma proteins, increased mesangial matrix and ?***
Collagen seen on trichrome stain (stains collagen blue)
You may also see marked atrophy of tubules, irregular interstital fibrosis and what in Chronic Glomerulonephritis (CGN)?
arterial and arteriolar sclerosis
in Chronic Glomerulonephritis (CGN) patient smay present with loss of appetite, anemia, vomiting or weakness, edema, hypertension and what?
uremia = pericarditis / secondary hyperthyroidism
There are three main antecedents to Chronic Glomerulonephritis (CGN), including crescentic RPGN (90%), focal segmental glomerulosclerosis FSGS (50-80%) and?
Membranoproliferative GN (50%)
