Exam 2 Glomerulonephropathys Flashcards
where is the renal angle anatomically
lower border 12th rib and lateral border of erector spine muscle
describe direction of renal colic pain
from renal angle and goes down forward to groin
what components of the kidney are affected by disease
glomeruli, tubules, interstitium and blood vessels
what component of kidneys is mostly harmed by immune mediated processes
glomeruli
what area of the kidney is most affected by toxic or infectious agents
tubules
What is azotemia
elevation of BUN and creatinine, decreased GFR
what is pre-renal azotemia? causes?
post renal?
pre is hypoperfusion of the kidneys: shock, hemorrhage, volume depletion, CHF
post is obstructed urine flow in distal calyces and pelvis
what is uremia
azotemia and a constellation of clinical signs and symptoms
What GFR level is indicative of uremia
<20
What are common imaging techniques of the kidney and associated GU organs
KUB- plain abdominal film
renal tomography
IVP
retrograde pyelography
what imaging techniques are used to evaluate ureter, bladder and urethra
cystography and voiding cytourethrography
how does Nephrotic syndrome lead to edema
proteins leaking out of plasma so lose oncotic pressure pull and fluid follows
What are your main Ddx for edema
kdiney disease, heart(CHF), liver(decreased production of proteins), GI tract (protein losing enteropathies), Lungs
do plasma proteins have neg or + charge
negative so move towards postive pol in electropheresis
Do we regularly do renal biopsies,
no because extremely hard to get to. retroperitoneal.
not worth risk
say on a serum strip patient has alot of IgG and Igkappa but not much else
multiple myeloma
What are signs of a nephritic syndrome
grossly visible hematuria, mild to moderate proteinuria, HTN
What is RPGN
rapidly progressive glomerulonephritis with a rapid decline in GFR (hours to days)
what are signs of Acute Kidney injury
rapid decline in GFR
oliguria or anuria
can result from glomerular, interstitial, vascular or acute tubular injury
can be reversible
what are signs of chronic kidney disease
milder-really not noticeable severe- uremia diminished GFR <60 ml/min for at least 3 months persistent albuminemia generally irreversible
What is criteria for ESRD
GFR <5% of normal
What syndromes are characteristic of glomerular disease
nephritic, nephrotic, asymptomatic hematuria or proteinuria, chronic renal failure, acute renal failure, renal tubular defects
what syndromes are characteristic of tubulointerstitial disease
nephrolithiasis, renal tumor, UTI, urinary tract obstrcution, renal tubular defects, acute renal failure
what is criteria for proteinuria in nephrotic syndrome
> 3.5 g/day
What are signs of nephrotic syndrome
heavy proteinuria >3.5, hypoalbuminemia <3g/dL, severe generalized edema, hyperlipidemia, lipiduria
what occurs to RAAS system with edema from proteinuria
activates renin release, so down path causes vasoconstriction of the afferent to kidney which just causes more problems.
selective proteinuria means what
albumin and transferrin, low MW proteins
what disease is pure nephrotic syndrome
minimal change disease
Why is hyperlipidemia assoc with nephrotic syndrome
the liver is trying to increase circulating proteins
why is thrombosis a risk with nephrotic syndrome
because may be losing endogenous anticoagulats
what are the systemic causes of nephrotic syndrome
DM, amyloidosis and SLE
what primary glomerular lesions lead to nephrotic syndrome
minimal change disease, membranous glomerulopathy, and focal segmental glomerulosclerosis
what is the renal corpuscle
glomerulus and bowmans capsule
what type of epithelium surround urinary space
squamous epithelium
acute kidney injury usually occurs where in the kidney
proximal tubules
What is criteria for chronic kidney disease
GFR<25%
where is the mesagium in the kidney
at the axis of the glomerulus
What are the layers of the glomerulus
capillaries have fenestrated endothelium then the BM has lamina rara interna , lamina densa, lamina rare externs then there is the visceral epithelium (podocytes)
What does the PAS stain on glomerulus
glycoproteins
What is the role of mesangial cells
contractile, phagocytic, proliferate and lay down matrix/collagen, also able to secrete some mediators
What is filtered easily in glomerulus
water and small solutes
proteins less than 3.6 nm
what is the barrier to proteins
the negative charge in BM repels proteins
also size of filtration slits
What are the slit diaphragm proteins
nephrin and podocin with actin cytoskeleton
What could cause the appearance of hypercellularity in the glomerulus
cellular proliferation, leukocyte infiltration, crescent formation
What are the 3 forms of BM thickening
- amorphous deposits like IC on either side, fibrin or amyloid, cryoglobulins etc
- increased syntehsis BM proteins (DM)
- additional BM in subendothelial locations
Hyalinosis is characteristic of what disease
focal segmental glomerulosclerosis FSGS
What is Sclerosis
extracellular collagenouse matrix ECM that builds up in mesangium (usually involves capillary loops)
results in fibrous adhesions
What is diffuse sclerosis
all glomeruli are affected
what is focal sclerosis
only some glomeruli are affected
what is segmental sclerosis
only parts of glomeruli are affected
What are the fixed intrinsic tissue Ag that cause Ab-mediated injury in glomerulus
NC1 domain of collagen IV Ag
Heymann Ag “megalin” which is a phospholipase A2R
msangial Ag like IgA nephropathy
What is Goodpasture syndrome caused by
anti GBM Ab cross react with lungs and kidney BM
what is the histo of goodpastures
linear pattern on IF
crescenteric glomerular damage
What does the histo of membranous glomerulopathy look like
subepithelial granular pattern on IF
What are the endogenous planted Ag that can lead to Ab mediated glomerular injury
DNA< nuclear proteins, Ig, IC and IgA
what are the exogenous planted Ag that can lead to Ab mediated glomerular injury
infectious agents and drugs, bacterial products
What is the staining pattern of planted Ag in glomerulopathy
granular
What can cause endogenous deposition of premade IC
DNA(SLE), tumor Ag
what can cause exogenous deposition of premade IC
infectious products, strep, hep B, C
Treponema pallidum, plasmodium falciparum
describe IC deposition based on IC charge
anionic will deposit subendothelial b/c can;t cross BM
cationic will cross and make it to the sub epithelial space
where is the subepithelial region
between outer GBM and podocytes
“humps”
subepithelial humps are characterisitic of what disease
acute glomerulonephritis
epimembranous deposits are characteristic of what diseases
membranous nephropathym, heymann glomerulonephritis
subendothelial deposits are characteristic of what diseases
SLE nephritis
membranoproliferative glomerulonephritis
mesangial deposits are characteristic of what disease
IgA nephropathy
what is unstoppable once GFR is 50% normal rate
steady rate of progression to ESRF
What is an example of a complement glomerulonephropathy
MPGN type II, dense deposit disease
What is the most common nephropathy worldwide
IgA nephropathy
Which type of deposit causes the spike and dome pattern
epimembranous
so membranous glomerulonephropathy
What usually is culprit of acute proliferative glomerulonephritis
group A beta hemolytic strep
what are the morphologicaly changes assoc with acute proliferative GN
marked hypercellularity, leukocyte infiltration, subpeithelial hump of IC
neutrophils in the lumen
granular deposits of IgG IgM and C’3 in the masangium
what is typical presentation of post strep GN
age 6-10
after pharyngitis or skin infection
malaise, fever, nausea, oliguria and hematuria 1-2 weeks after recovery from a sore throat
RBC casts, mild proteinuria, periorobital edema and mild/moderate HTN
what is adult presentation of post strep GN
more atypical and aggressive course
may exhibit sudden HTN or edema, frequently with elevated BUN
what is the prognosis of post strep GN in children?
95% recover completely with just water an salt restriction
what is the prognosis of post strep GN in adults?
60% recover with no sequellae
some progress to RPGN or prolonged time to resolution, progress to chronic glomerulonephritis
what can cause acute proliferative GN non-strep
other bacteria *staph have IgA not IgG**
viral syndromes: Hep B C, mumps, HIV, varicella
sequel to parasitic infection, malaria, toxoplasmosis
What are the 3 major types of rapidly progress GN RPGN
type I is Anti-GBM Ab
type II is IC deposition
type III is pauci-immune
what are examples of anti-GBM Ab diseases that can turn into RPGN
renal limited
Good pasture syndrome
What are examples of diseases that can lead to RPGN from IC deposition
post-strep (acute prolfierative glomerulonephritis)
lupus
henoch-schonlein purpura
IgA nephropathy
What are types of Type III RPGN
ANCA-associated, idiopathic and granulomatosis with polyangiitis
50% of primary renal diseases associated with RPGN have what type pattern
type III pauci immune
What HLA subtype is associated with goodpastures
HLA DRB1
genetic predisposition to autoimmunity
What is the main route of Tx for goodpastures
plasmapheresis to remove pathogenic circulating Ab is part of effective Tx regimen which includes immunsuppressive therapy
What is Tx method for type II RPGN? type III?
does not typically respond to plasmapheresis so Tx if focused on underlying disease
same for type III
What is ANCA and what is it assoc with
antineutrophil cytoplasmic Ab type III RPGN and may have a role in vasculitis
What is the main protein in BM that repels albumin
heparin glycoprotein
What does RPGN look like morphologically
cresenteric formation in glomeruli from proliferation of parietal epithelial cells
What is the clinical presentation of RPGN
hematuria, RBC casts in urine, moderate proteinuria, variable HTN and edema
what are signs of goodpastures
hemoptysis and pulmonary hemorrhage
What are normal protein levels in 24 urine
<150 mg
What primary glomerulopathies can cause nephrotic syndrome? state whether more common in children or adults
membranous glomerulonephropathy(adults) minimcal change disease (children!) focal segmental glomerulosclerosis(adults) membranoproliferative glomerulonephritis(children=adults) IgA nephropathy (adults)
what percent of nephrotic syndromes in children is due to primary glomerular disease in US
95%
what percent of nephrotic syndromes in adults is due to primary glomerular disease
60%
usuallydue to systemic process
What are the systemic diseases that lead to renal disease
DM, SLE, amyloidosis, drugs, infections, malignancies, allergic reactions and random hereditary causes
what 3 diseases are pure nephrotic syndromes
minimal change
membranous glomerulopathy
focal segmental glomerulosclerosis
What HLA is postulated to be linked to primary membranous glomerulopathy
HLA DQA1 which is assoc with Ab to PLA2R that has interactions with C’ and the MAC complex
what are the deposits made of in primary membranous glomerulopathy?
secondary?
IgG4
secondary is IC
is the proteinuria selective or non in membranous glomerulopathy
nonselective
What is morphology of membranous glomerulopathy
marked diffuse thickening capillary walls without increase in cellularity
5-20 fold increased thickness in BM
spikes and domes from the deposits (sub epithelial)
effaced foot processes
What are signs of membranous glomerulopathy
Sudden onset nephrotic or nonnephrotic proteinuria with microscopic hematuria and mild HTN
increased serum creatinine and HTN as it progresses
What is the prognosis of membranous glomerulopathy
60% have persistent proteinuria
40% develop renal insufficiency
10% progress to ESRD
What is the most common cause of nephrotic syndrome in children
minimal change disease
when is the peak incidence for minimal change
2-6 yrs old
after respiratory infection or immunization
What is Tx for minimal change
corticosteroid therapy
What type of cancer is minimal change assoc with
hodgkin lymphoma or other lymphoreticular disease
What are the presenting signs of minimal change
massive proteinuria–> edema!
highly selective for albumin
no HTN or hematuria
What is the differentiating characteristic of minimal change and membranous glomerulopathy since both have podocyte effacement
in minimal change still have normal glomeruli
Where do you see lipid accumulation in the kidneys in minimal change
proximal tubules
What do you see under IF in minimal change disease
nothing, there are not dense deposits of anything
glomeruli pretty normal appearing
On IF you see granular IgG and C’3 in GBM in the mesagium
primary on Ddx?
acute proliferative glomerulonephritis- nephritic
on IF you see linear IgG and C’3 with crescenteric formation
primary on Ddx?
Goodpastures- nephritic RPGN
on IF you see granular IgG and C’3 diffusely
primary on Ddx?
membranous glomerulopathy- nephrotic
on IF you see focal IgM and C’3
primary on Ddx?
focal segmental GS
nephrotic
On IF you see IgG + C’3 and C1q and C4
primary on Ddx?
MPGN type I
On IF you see IgG and C’3 but not C1q or C4
patient has hematuria and renal failure
what do you suspect?
MPGN type II
dense deposit
What is the most common cause of nephrotic syndrome in US adults
primary FSGS
what is the demographic distribution of FSGS
most common in hispanics and african american
What other diseases are assoc with FSGS
HIV, heroid addiction, sickle cell and morbid obesity
What are the renal complications assoc with HIV FSGS
acute renal failure, acute interstitial nephritis, thrombotic microangiopathies, post infectious glomerulonephritis
What is the most severe complication of HIV FSGS? describe it morphologically
collapsing FSGS
retraction or collapse of entire glomerular tuft
cystic dilation of tubule segments with inflammation and fibrosis
proliferation and hypertrophy of podocytes
can be assoc with the drug pamidronate
What genes are assoc with rare FSGS inherited forms
NPHS1 css 19q13 encodes nephrin
NPHS2 autosomal recessive css 1q25-31 encodes podocin
autosomal dominant FSGS from alpha gactinin 4 which is a podocyte actin binding protein
TRPC6 mutations in adult onset FSGS causing an increase in intracellular Ca
css 22 mutations in APOL1(protects against trypanosome infections)
who have better prognosis with FSGS children or adults
children
what is the clinical presentation of idiopathic FSGS
higher incidence hematuria, reduced GFR and HTN
proteinuria is nonselective
poor response to corticosteroids
significant progression to chronic kidney disease(atleast 50% progress to ESRD in 10 years)
what parts of glomerulus are affected in MPGN
glomerular proliferation is predominantly mesangial
what is clinical presentation of MPGN type I primary
children
nephrotic
microscopic hematuria
mild HTN
what is prognosis for primary type I MPGN patients
50% develop chronic renal failure over a 10 year span
describe clinical presentation of secondary MPGN type I
occurs in adults frequently associated with chronic antigenemia from: infection, autoimmune or neoplasia occurs with Hep B, C with cryoglobulinemia SLE, endocarditis alpha1 trypsin deficiency HIV schistosomiasis malignancies
what is clinical presentation of MPGN II
occurs in children gross hematuria with nephrotic or subnephrotic proteinuria profound hypocomplementemia frequent recurrence no IgG deposition
what causes hypocomplementemia in dense deposit disease
persistent C3 activation from C3 nephritic factor circulating around
where are the deposits seen on IF for type I MPGN
subendothelial
what type of MPGN I is most common
secondary
What is the most common cause of glomerulonephritis world wide
IgA nephropathy
What is Berger disease
Renal IgA without systemic disease
What is HSP henoch schonlein purpura
IgA nephropathy assoc with systemic disease with skin manifestaions and involvemnent of abdominal viscera
describe demographics of IgA nephropathy
primarily in older children 2nd and 3rd decades
caucasians and asians> african americans
male predominance 2:1
family history +
What is the clinical presentation of IgA nephropathy
microscopic hematuria with presence of significant infection at certain body sites and recurrence of infection at same site
What other diseases are IgA nephropathy assoc with
gluten enteropathy and liver disease
What is detected in IF of IgA nephropathy
IgA deposits, C3 and properdin but not really IgG IgM
what percent of patients with IgA nephropathy progress to chronic renal failure
15-40%
very slow process
what is the demographics of Alport Syndrome
ages 5-20
X linked form
male express full syndrome, females carriers with hematuria
what are signs of alport syndrome
chronic renal failure, hematuria, nerve deafness, various eye disorders
defects in colagen IV
What are the genetics behind alport X linked vs autosomal
X lnked is on COL4A5
autosomal on COL4A3 or COL4A4
describe morphological appearance of alport syndrome
frayed GBM so looks like basket weave or frayed
what is thte clinical presentation of alports
microscopic hematuria, red cell casts in urine
proteinuria sometimes
hearting issues age 5-20
What is the most common cause of benign familial hematuria
Thin Basement Membrane lesion
What mutations are assoc with thin basement membrane lesion
mutations in alpha 3 or 4 chains of type IV collagen
What is the inheritance pattern of thin basement membrane liesion
autosomal
What are the most common leading causes to chronic glomerulonephritis
crescenteric is 90% membranous nephropathy 30-50% MPGN 50% IgA nephropathy 30-50% FSGS 50-80%
SLE patients are more likely to present with nephritic or nephrotic syndrome?
nephritic
What are the deposits in SLE nephritis and what are they composed of
IgG and C’ in the subendothelium
what type of glomerular pattern is seen with DM
nodular glomerular sclerosis “Kimmelstiel Wilson disease”
and hyalinizing sclerosis in arteries
one of leading causes of chronic renal failure in US
DM nephropathy patients have increased risk for what renal pattern
pyelonephritis and papillary necrosis
what is clinical presentation of DM nephropathy
microalbuminuria
non nephrotic proteinuria
nephrotic syndrome
ESRD
What is presentation of Amyloidosis and stain color?
nephrotic syndrome and die of uremia
stain congo red
What is presentation of essential mixed cryoglobulinemia
systemic deposits of IgG IgM and ICs
cutaneous vasculitis, synovitis, MPGN type I
What does Multiple Myeloma present with in kidneys
proteinuria or nephrotic syndrome, HTN and progressive azotemia
What is physical signs of Henoch Schonlein purpura
skin lesions of extensor surfaces of arms lefs, butt and abdomen
What age gorup is most affected by henoch sconlein purpura
kids ages 3-8
What are the 2 major processes that lead to glomerular nephropathy
metabolic defect linked to hyperglycemia and advanced glycosylation end products that thicken the GBM and increase mesangial matrix
Hemodynamic effects associated with glomerular hypertrophy contribute to the glomerulosclerosis
What would you expect to see on CT of end stage diabetic kidneys
they are shrunken
which disease has the cahracterization of “wired looped GBM”
the subendothelial dense deposits seen with SLE
describe morphology of diffuse proliferative lupus nephritis
marked increase in cellularity
glomerulus is increased and seems stuffed into Bowmans capsule with decrease in urinary space
What are the two types of acute kidney injury
ischemic and nephrotoxic
what are common causes of ischemic acute kidney injury
decreased effective circulating volume like from hypotension and shock
diffuse involvement of intrarenal blood vessels in conditions like malignant HTN, microangiopathies and systemic conditions associated with thrombosis: HUS, TTP or DIC
what cause nephrotoxic AKI
drugs, metals, toxins
What are the less common types of Acute Kidney Injury
acute tubulointerstitial nephritis
urinary obstruction
Which area of kidney is susceptible to ischemia and why
the proximal tubular epithelial cells have high energy requirements
what causes the obstruction in ischemic AKI
the necrotic tubular epithelial cells are detached and sloughed into tubular lumen causing obstruction
What will it look like morphologically after ingestion of ethylene glycol
the proximal tubular epithelial injury is widespread with all cells exhibiting swelling and vacuolization
What are the phases of acute tubular injury
Initiation- 36 hrs oliguria
Maintenance- oliguric crisis with uremia, hyperkalemia
Recovery-large urine volumes, large loss of water Na K, hypokalemia, susceptibility to infection
HepC cryglobulinemia is assoc with what glomerulopathy
MPGN type I
majority of SLE patients present with nephrotic or nephritic syndrome?
nephritic
bacterial endocarditis is associated with what glomerulopathy
acute proliferative glomerulonephritis
kimmelstiel-wilson disease is synonymous with what
DM glomerulsclerosis
nodular
