Pathology of Nephritic Syndrome

Question 1

Asymptomatic proteinuria/hematuria

1) symptoms
2) Urinalysis shows…

Answer 1

1) asymptomatic
2) proteinuria (> 150 mg/24 hr)

hematuria = dark or normal color urine + RBCs + red cell casts

Question 2

Etiologies of asymptomatic proteinuria/hematuria

Answer 2

Proteinuria = leakage of protein thru glomerular basement membrane (glomerular disease) NOT TUBULAR

Hematuria = red cell casts = glomerular bleeding

Question 3

Causes of leakage in basement membrane and what leaks thru

Answer 3

1) loss of electrostatic neg charge barrier so albumin leak thru
2) loss of size barrier so albumin, globulin and protein leak thru

Question 4

Acute nephritic syndrome

1) signs and due to?
2) how does GFR change
3) effects of change in GFR
4) time frame

Answer 4

1) hematuria and proteinuria due to incr glomerular capillary permeability
2) decr GFR
3) Na+/H2O retention –> edema, CHF, HTN

azotemia (incr creatinine and BUN)

hyperkalemia

4) hours to days

Question 5

Rapidly progressive nephritic syndrome

1) signs and due to?
2) how does GFR change
3) effects of change in GFR
4) time frame

Answer 5

1) hematuria and proteinuria due to incr glomerular capillary permeability
2) VERY DECR GFR
3) more fluid retention, more azotemia, oliguria
4) longer version of acute nephritic

Question 6

Nephrotic syndrome

1) signs and due to?
2) effect on plasma oncotic pressure
3) effects of change in oncotic

Answer 6

1) massive proteinuria (> 3.5 g/24 hrs) not compensated by hepatic albumin syntheiss
2) decr plasma oncotic pressure
3) Na+ and H2O retention, edema, hypercholesterolemia

Question 7

Chronic renal failure

1) due to
2) how does it affect GFR
3) assoc with
4) etiologies

Answer 7

1) nephron loss
2) decr GFR
3) uremia
4) glomerular disease, vascular disease/HTN (MOST COMMON), infection, drugs/toxins, UTI

Question 8

Morphologic pattern of glomerular disease

Answer 8

1) mesangial, endocapillary, epithelial (podocyte) = crescent proliferation
2) leukocyte infiltration = PMN’s or leukocytes
3) basement membrane thickening/changes
4) sclerosis (segmental or global)

Question 9

1) mesangial, endocapillary, epithelial (podocyte) = crescent proliferation
2) leukocyte infiltration = PMN’s or leukocytes
3) basement membrane thickening/changes
4) sclerosis (segmental or global)

indicative of…

Answer 9

glomerular disease

Question 10

Distinguish between focal/diffuse sclerosis

Answer 10

Of all total glomeruli

focal = some normal, some abnormal

diffuse = affects all glomeruli

Question 11

Distinguish between segmental/global sclerosis

Answer 11

within individual glomerulus

segmental = only portion of one

global = entire glomerulus

Question 12

Things to identify on immunofluorescence

Answer 12

1) Ig’s/complement
2) distribution (mesangial/capillary)
3) pattern (linear/granular)

Question 13

Things to identify on electron microscopy

Answer 13

1) deposits of Ag-Ab complexes
2) GBM changes

Question 14

Things to identify on serum

Answer 14

1) complement levels (decr in some acute GN’s)
2) ANA- SLE
3) ASO (anti-strep O) = post-strep GN
4) ANCA = Wegener’s, PAN

Question 15

IF you see ASO on serum what could that indicate?

If you see ANCA on serum what could that indicate?

Answer 15

1) post-strep GN
2) Wegener’s, PAN

Question 16

Thin Basement Membrane Disease

1) also known as
2) prognosis
3) mutations in…
4) diagnsois based on …

Answer 16

1) benign familial hematuria
2) excellent
3) alpha chains of collagen IV (thin basement membrane)
4) electron microscopy)

Question 17

Alport’s disease

1) triad of …
2) due to mutation in…
3) inheritance
4) can’t form …
5) definitive diagnosis based on what?
6) progress to…

Answer 17

1) nephritis, deafness, ocular lesions
2) alpha-5 chain of collagen IV
3) X-linked
4) normal basement membrane
5) basket-weave pattern on EM (abnormal lamina densa)
6) ESRD

Question 18

Signs of non-inflamm pathogenesis DUE TO OXIDATIVE

1) mediated by…
2) immune complexes activ …
3) damages …

Answer 18

1) circulating factors or Ig’s that bind to membranes of glomerular epithelial cells
2) activ GEC to release reactive oxidants/proteases that damage diaphragms btwn podocytes
3) cause GEC to detach from basement membrane –> leak

Question 19

Signs of non-inflamm pathogenesis DUE TO COMPLEMENT

1) mediated by…
2) antibodies bind…
3) damages …

Answer 19

1) complement-fixing anti-GEC antibodies
2) antibody bind GEC –> activ complement membrane attack complex
3) poke hole in glomerular basement membrane, incr permeability

Question 20

Inflammatory pathogenesis of glomerular disease usually involves (4)

Answer 20

1) PMN’s
2) macrophages
3) mesangial cells
4) T cells

Question 21

how are PMn’s involved in leading to inflamm pathogenesis

Answer 21

1) Ig antibody deposits within capillaries
2) activ complement
3) infiltrate of PMN’s
4) PMN’s burst –> release ROS –> damage glomerular basement membrane and endo cells
5) fibrin deposit in Bowman’s space –> form CRESCENTS

Question 22

if crescents form what does that indicate

Answer 22

fibrin in bowman’s space –> severe inflammation

Question 23

If Ig bind to endogenous antigens, what diseases

If Ig bind to EXOGENOUS antigen, what disease

Answer 23

1) SLE, good pasture’s
2) infection or toxin

Question 24

macrophage role in inflamm disease

Answer 24

1) macrophage activ by cytokine
2) release oxidants and proteases that damage glomerular basement membrane
3) macrophage release cytokines that stim sclerosis

Question 25

mesangial cell role in inflamm disease

Answer 25

1) immune complex, complement, cytokine activ mesangial cell
2) release oxidants, proteases, growth factors, ECM

Question 26

T cell role in inflamm disease

Answer 26

1) T cells activate macrophage and mesangial cells

Question 27

What is endocapillary hypercellualrity mean?

What is the marker of mesangial hypercellularity

what are crescents a reaction to?

Answer 27

both mesangial and endothelial cells in vascular compartment

> 2-3 mesangial nuclei per island

severe injury to glomerular capillaries –> fibrosis in Bowman’s space

Question 28

Describe cellularity, segmental vs.global, capillary loops

Answer 28

Hypercellular? yes, mesangial hypercellularity

Segmental or global? segmental

Capillary loops still open

Question 29

Answer 29

Left = immune complexes deposited in mesangial region

podocytes intact

basement membrane intact

Right = IgA deposited in mesangial regions

Question 30

IgA neuropathy

1) usually presents as …
2) often coincides with …
3) morphology on stain
4) on EM, on IF
5) therapy
6) prognosis

Answer 30

1) asymptoamtic hematuria
2) nephritic or nephrotic; with URI or GI infection, or liver disease
3) mesangial, focal (can be MPGN)

4)

EM = mesangial deposits

IF = mesangial IgA

5) ? steroids
6) ESRD

Question 31

Henoch-Schonlein Purpura

1) also known as
2) due to …
3) may involve
4) renal biopsies look like …
5) patient population

Answer 31

1) systemic IgA vasculitis
2) systemic deposition of IgA immune complex
3) kidney, skin, joint, GI
4) IgA nephropathy but more endocapillary prolif or crescents
5) < 10 yrs post URI esp strep

Question 32

Answer 32

Left = hypercellular, no open capillary, inflamm cells (PMN’s)

creatinine = 2.5, RBC and RBC casts in urine = nephritic

Right = diffuse global endocapillary proliferative GN

Question 33

Answer 33

Subendothelial Hump-like depositis

left: red = humps

right = fenestrated endothelium too many cells inside

Question 34

Answer 34

left = hypercellularity in capillary loop

subepithelial deposits

right = starry sky pattern = granular with IgG/C3 immune complexes

Question 35

Postinfectious GN

1) usually due to
2) acute nephritic or nephrotic
3) morphology
4) on EM, IF, serology
5) therapy
6) __% of children recover, __ % OF ADULTS recover

Answer 35

1) post strep infection
2) acute nephritic
3) diffuse prolif, exudative GN
4) EM = subepithelial hump-like deposits

IF = granular GBM = starry sky

serology = elev ASO

5) supportive
6) 99, 60

Question 36

Answer 36

left = necrotizing and crescent glomerulonephritis

karyolectic debris

right = proliferation = crescents in bowman’s space

Question 37

Answer 37

left = ruptured capillary loop

Question 38

Crescentic glomerulonephritis

1) crescents = sign of ___
2) caused by ___
3) present as ___
4) more crescents correl with ___
5) glomeruli will usually ___

Answer 38

1) severe acute glomerular disease
2) fibrinoid necrosis of capillaries
3) RPGN
4) serum creatinine levels and prognosis
5) heal with scar

Question 39

FSGN and Crescentic glomerulonephritis

If you see linear staining on IF …

IF you see granular staining …

If you see no staining …

Answer 39

1) goodpasture’s, anti-GBM
2) IgA, SLE, endocarditis, Idiopathic
3) wegener’s, microscopic PAN, churg-strauss, idioapthic

Question 40

Answer 40

left = linear staining for IgG

right = starry sky = postinfectious GN presents as rapidly prolif

Question 41

FSGN, crescentic GN

Serum/blood studies

1) if you see anti-GBM antbodies…
2) ANA, anti-dsDNA, complement depletion (C3, C4)
3) ANCA (MPO- cationic protein fixing complement)
4) blood cultures

Answer 41

1) goodpasture
2) lupus
3) vasculitis
4) endocarditis

Question 42

Anti-gbm disease

1) ___ IgG antibody
2) antibodies directed against ___
3) if renal limited, ___
4) if renal + lung, ___
5) classic presentation =
6) on IF?

Answer 42

1) nephrotoxic
2) alpha chain of collagen IV in basement membrane
3) anti-GBM
4) goodpasture
5) RPGN + hemoptysis
6) linear

Question 43

Crescentic GN

1) usually __
2) therapy
3) prognosis

Answer 43

1) RPGN
2) steroids, cytotoxics, plasmaphoresis
3) poor

Question 44

lupus nephritis

1) part of ___
2) IF shows…
3) present as …
4) prognosis

Answer 44

1) SLE
2) full house = granular with positive IgG, IgA, IgM, C1q, C3

3) nephritic syndrome, RPGN, nephrotic syndorme, or mixed nephritic-nephrotic
4) usually good with treatment

Question 45

Answer 45

anti-gbm disease

Question 46

Answer 46

left = diffuse glomerulonephritis, hypercelllular, endocapillary prolif, PMN’s thick peripheral capillary loop

right = wire loop lesions= very red and huge deposits

Question 47

Question 48

Normal glomerulus is 70% ___

Largely contains ___

Features of mesangial cells

Answer 48

1) space
2) largely mesangial cells
3) derived from monocytes; produce matrix that surrounds self and interdigitates with capillary loops; phagocytose; intravascular

Question 49

what is the most selective barrier for filtration

made of?

what is the largest filterer of proteins

Answer 49

slit diaphragm = podocytes connected by thin line slits

made of nephrin (2 nephrins holding hands + adhesion molec holding podocytes to basement membrane

basement membrane = leaky so podocytes are most stringent

Question 50

nephrotic syndrome

1) presents with ___
2) due to ___
3) leads to…

Answer 50

1) massive proteinuria (> 3.5 g/24 hr)
2) decr plasma oncotic pressure
3) severe edema, hypercholesterolemia, lipiduria

Question 51

Hyperfiltration causing glomerular disease seen in ..

Answer 51

diabetics

segmental glomerulosclerosis

Question 52

loss of glomerular polyanions

how cause glomerular disease

Answer 52

incr permeability of glomerular capillary wall –> lose albumin in urine –> decr plasma oncotic pressure –> fluid into extravascular