Renal - Glomerulonephritis and Tubulointerstitial Disease

1) mesangial cells
2) endothelial cells
3) visceral epithelial cells (podocytes)

true

Fenestrated endothelial cell cytoplasm

TRUE this is KEY

1) immune complex-associated glomerular lesions, that have a granular appearance
2) Anti-GMB-mediated glomeruloneprhitis that has a continuous linear staining of the GBM.

They are assembled LOCALLY (b/c an intact complex won't go thru BM) - when Ab is filtered through and binds to filtered/intrinsic antigen

- effacement of foot processes and nephrotic syndrome
- inflammatory process does not occur b/c the complement doesn't contact inflammatory cells
- underlying disease takes a while for deposits to clear and resolution of proteinuria (months/years)

- usually entrapment of circulating immune complexes, via exogenous (bacteria/virus) or endogenous (DNA, tumor) to the body.

Inflammation that tears holes in BM, inflammatory cells that plug GFR lumen and decrease GFR (lots of bad things). This is a more severe than subepithelial and more acute, BUT it does clear faster.

the alpha-3-chain of type IV collagen in the basement membrane, leading to linear (not granular) staining

1) nephrotic syndrome - >3.5g proteinuria, lipiduria, hypolabuminemia, hyperlipidemia
2) acute nephritic syndrome - hematuria, azotemia, proteinuria, oliguria, edema, HTN
3) rapidly progressive GN - acute nephritis, proteinuria, and acute renal failure
4) asymptomatic hematuria/proteinuria - glomerula hematuria, subnephrotic proteinuria
5) Chronic Renal Failure - azotemia progressing over years to uremia

acute nephritic syndrome

1) proteinuria > 3.5g/day
2) Hypoalbuminemia
3) Hyperlipidemia
4) LIpiduria
5) Edema (mostly due to sodium retention rather than hypoalbuminemia)

a structural abnormality shared by all nephrotic conditions is diffuse simplification or "fusion" of the foot processes of podocytes

sodium retention (not hypoalbuminemia)

1) injurty in glomerular capillary wall that results in leak of protein
2) serum albumin and protein depletion
3) hyperlipidemia results from synthesis of lipoporteins, triggered in part by hypoalbuminemia

1) injury glomerular epithelial cell - cytokines released by mononuclear cells may be responsible for this in FSGS
2) immuen complex formation and complement activation in subepithelial space (membranous GN)
3) deposition diseases affecting the GMB (amyloidosis or diabetes)

1) minimal change disease
2) focal segmental glomerulosclerosis
3) membranous nephropathy

minimal change disease

rapid onset of edema (overnight)
selective proteinuria (just albumin)
normal renal function (normal creatinine)
No HTN or Hematuria

minimal change disease

overproduction of angiopoietin-like 4 (ANGPTL4) inside the podocytes, which is normally expressed at low levels but is highly upregulated in MCD
- this protein will bind to GBM, causing diffuse effacement of foot processes and loss of GBM charge (due to deficieincy in sialic acid residues)

- fusion/effacement of foot processe (seen best in EM)

TRUE

- steroids have immediate affects, repases are common, and you keep giving steroids. But the course of the disease doesn't lead to chronic renal disease traditionally

false. it doesn't

FSGN

Insidious development of nephrotic syndrome and non-selective proteinuria; many patients have some hematuria, HTN, and decreased GFR (elevated creatinine)

visceral epithelial cell injury probably due to some sort of circulating factor

False. There are no immune complexes associated with it.

hyalinosis and sclerosis that represents entrapment of plasam proteins with increased extracellular matrix deposition

- Nephrin and podocin (slit diaphragm proteins) and alpha-actinin 4 (actin binding proteins) mutations that are normally found at slit diaphragm

- mature podocytes don't proliferate, and ones that are left are stretched, causing loss of support of capillaries, so segments of loop are dilated and for fibrous attachment ot bowman capsule and eventually sclerosis (scarring).

in children, but not as beneficial in adults

not that well, they are not that responsive (children are a little better).

TRUE

- plasmapheresis to remove whatever the circulating factor is.

things that decrease renal mass:
1) unilateral renal agenesis
2) reflux nephropathy (that scars glomerulus), pyelnonpehritis (chornic)
3) primary glomerulopathies
4) sickle cell
5) arteiral and arteriolar scerosis
6) renal allograft recipients

1) reduction in renal mass causes HTN in glomerulus and glmeruluar hypertorphy
2) mesangial cell hyperpalsia, ECM deposition, causing endoethieal/epitehilal injury, leading to...
3) focal glomerulosclerosis

ACEi and ARBs that lower intraglomerular capillary pressure.

In SECONDARY you don't see fusion/effacement of foot processes in other places, but in PRIMARY, in other places apart from sclerosis lesion, there is diffuses fusion of foot processes

Membranous glomerulonephritis

Antibodies against phospholipase A2 receptor on podocytes

1) Abs against phospholipase A2 on podocyte
2) tumor antigens, HBsAg, SLE
All this leads to action of complement (C5-C9) on epithelial cells

1) more matrix, w/ thicker GBM
2) IF reveals granular staining to IgG

darker deposits sitting on top of BM, eventually surrounded by "spikes" completely around deposits, forming intra-membranous deposit

True

1) MOST- idiopathic
2) OTHER - SLE
3) small other - infectious (HepB/C, syphilis, schistosomiasis, malaria)
4) tumors (lung and colon)
5) drugs (penicillamine, gold, captopril)

hep B/C
Syphilis
Schistosomiasis
Malaria

1) idiopathic
2) SLE
3) tumor (esp lung/colon)

- insidious development (swelling, foaming of urine, that's about it)
- variabable course wehre
1/3 - spontaneous remission
1/3 - have persisitent proteinuria and stable renal function
1/3 - renal failure
- steroids not beneficial

False. They aren't

minimal change

- active urine sediment containing red cells, white cells, and cellular and granular castls
- urinary abnoamrlities refelct the influx of infalmmatory cells
- type and severity of glomerular inflammation determines level of kidney dysfunction

A glomerular disease (white cell cast is not as specific)

1) immune complex formation and complement activation in mesangium or subendotheilal space
2) circulating Abs against neutrophil antigens in systemic vasculitits ANCA), neurophil activation injuries capillary walls
3) circulating abs directed against GBM

- sudden elevation in plasma creatinine
- fall in GFR due to decrease in surface area, b/c capillary lumens get clogged with inflammatory cells
-sudden reduction in GFR induces sodium retention, edema and HTN

1) acute proliferative glomerulonephritis
2) membranoproliferative glomerulonephritis

Diffuse proliferative GN

Group A B-hemolytic strep (or sometimes Hep C, staph aureus, some other bacteria)

typically 1-4 weeks after infection, the time required for antibody production and formation of immune complexes

all glomeruli involved (progresses in hours, VERY acute). No capillary lumen bc of hypercellularity, inflammatory cells (PMNs), expansion of glomerulus (swells)

"starry sky" pattern, big clumps of immune complexes that are not continuous, corresponding to large "hump" composites.

On the (subepithelial?) side of the BM, w/ no spike formaiton b/c they go away fairly quickly

membranous is more continuous granular deposits, diffuse is a little more spread out and "starry"

subepitheilal mostly (tho there is subendotheilal that attracks the inflammatory cells)

1) abrupt onset of hematuria, proteinuria, edema, HTN, and renal insufficiency
2) elevated titers to streptococcal products
3) low serum complement

1) acute postinfectious GN (a type of acute proliferative GN) b/c this is a very inflammatory disease the consume
complement
2) membranoproliferative GN

Acute/diffuse proliferative GN (a type of disease the is asscoiated with acute nephritic syndrome)

True
95% of children recover
60% of adults recover

Membranoproliferative is more chronic (associated with chronic infections, not just strep that goes away) . aka Hepatitis C

Hepatitis C and other chronic infections

1) BM thickening w/ endothelial and mesangial cell proliferation
2) nephrotic syndrome and acute nephritic syndrome together
3) hypocomplmementemia, caused by excessive consumption of C3

1) mesangial and subendothelial deposition of circulating immune complexes
2) we usually don't know antigen, something w/ infectious cause (chronic) like Hep C

Nature of dense depositis is unknown) - not immune complexes
- activation of alternative complement pathway (decreased C3 ,normal C1/4)
- Circulating IgG autoantibody called C3 nephritic factor binds to and stabilizes the C3 convertase

Well it is called Type II MPGN, so it's a TYPE of memtranoproliferative glomerulnephritis even though it's a different disease

Type II Membranoproliferative GN

The C3NeF stabilizes c3 convertase to break down more C3 to C3b, causing dense deposits to form.
The SAME disease (dense deposit disease) can happen if you have a deficieincy in I/H factor which normally degrades C3 convertase .

VERY hypercellular, difference in acute proliferatie is that MPGN has a lobular pattern b/c of thickened BM. You see double lines on a silver stain

MPGN

Fragments of mesangial cells stuck between new basement membrane essentially

1) idiopathic
2) Chronic infections - Hep B/C, endocarditis, infected ventriculo-atrial shunt, visceral abscess
3) SLE
4) Myeloproliferatie disease (esp monoclonal immunoglobulin disorder)

nephrotic OR nephritic
slowly progressing, no good treatment
50% develop chronic renal failure
High recurrence rate in transplanted kidneys, esp in Type II MPGN

1) associted w/ focal necrotizing and/or crescentic pattern of glomerular injury
2) active urine sediment present
3) takes longer to evolve than acute nephritic
4) do not have edema/HTN

1) focal necrotizing GN (less than half glomeruli ?)
2) Crescentic GN (more than half the glomeruli)

Seen in rapidly progressive GN, it's a mixture of epithelial cells and inflammatory cells that is adhreent to bowman's capsule

1) fibrous - more advanced and scarring
2) cellular - newer i think
- eveyrthing in between

Immune Complex - younger pt (lupus, severe igA)
ANCA - older
Anti-GBM - constant and rare

ANCA are abs to neutrophilic cytoplasmic antigens, and the ensuring inflammation affects small vessels, causing purpura, athralgia, myalgia, peripheral neurophaty, and pulmonary hemorrhage
- glomerulonephritis is a frequent componenet of small vessel vasculitidies

- crescentic GN
- pulmonary hemorrhage association (Goodpasture's)
- Due to Abs against type Iv collagen in the BM
- Trigger is unclear

Proteinuria, hematuria, and azotemia are ALWAYS present, and nephrotic syndrome isn't
- usually fatal if untreated

Steroids and Cytoxan results in cure in 90%, esp if caught early.

False

False. You don't see nephrotic syndrome in these

Circulating antibodies against the GBM

Patients picked up on routine exam... characterized by focal and usually segmental inflammatory lesions of the glomeruli or by basement membrane anomolies resulting incapillary fragility. Usually have normal plasam creatinine and normal bp

1) mesangilal glomerulonephritis (IgA nephropathy)
2) Glomerular basement membrane abnormalities (eg. alports and thin BM nephropathy)

IgA Nephropathy,

asymptomatic, w/ recurrent gross or microsocopic hematuria and mild proteinuira, more common in children and young adults, intitially presents following URI.

Often following a URI

1) Genetic or acquired abnormlity of immune regulation that leads to increased mucosal IgA synthesis in respones to respiraotyr or GI exposure of environmental agenst
2) IgA containing complexes are trapped in the mesangium, where they activated the alternative complement pathway.

occurs in pts w/ liver disease due to defective clearance of IgA complexes.

Hypercellular, expanded mesangial areas with normal capillary loops surrounding them. Strictly confined to mesangium

IgA nephropathy
SLE

1) 15-40% develop ESRD
2) no satisfactory treatment (fish oil?), tends to recur in transplant kidney
3) BUT, most pts are asymptomatic for the rest of their lives

treu

- classic hereditary nephritis: a sclerosing glomerular disease accompnaied by nerve DEAFNESS and various eye disorders
- most common presenting sign is gross heamturai
- X linked pattern, full blown disease most common in males (females rarely develop ESRD)

males

Defective GBM syntehsis, caused by mutations in genes encoding a5 chain of Type IV colagen (and some a3/a4 chains as well)

FSGS

intersitital foam cells of the kidney and focal segmental sclerosis

Basement membrane thinner AND, dead give away, is widening of basement membrane w/ splitting of lamina densa that makes a "basket weave pattern"

Alport's Syndrome

- presentation - persistent microscopic hematuria
- **often exacerbated by febrile illness
- minimal proteinuria, HTN, and progressive renal failure
- Mutation in A3/4 chains of collagen

- normal looking glomerulus but w/ red cells in bowman's space
- EM: thinner basement membrane

- slowly progressive renal failure
- increasing proteinuria nad variable hematuria
- structural equivalent of thi syndrome is ESRD, w/ global glomerular scerlosis, tubular atrophy, interstitial fibrosis, etc.

ESRD

1( primary forms of vascular injury
- thrombotic angiopathies
- malignant nephrosclerosis
- benign nephrosclerosis
3) various primary/secondary glomerulopathies that go to scarring
4) interstitail diseaes (talk about in next lecture)

Once a glomerular disease destorys functioning nephrons and reduces GFR by about half or so of normal (30-50%), progression to ESRD proceeds at constant rate, independent of original stimulus or activity of underlying disease :(

ACEi and ARBs

IgA Nephropathy

solutions used in colon cleansing to prep for colonscopy. These solutions aren't used as much

post-op

in acute tubular necrosis

- tubules flattens out and epithelium sloughs off
- granular debri in lumen
- tubule dilates and you can see lumen

acute tubular necrosis (over acute GN)

1) most common is ischemia - hypovolemia/shock, heart failure, vascular obstruction
2) nephrotoxic - drugs, radiographic agents, heavy metals/organic solvents

1) Tubular epithelial cells, sensitive to ischemia (most in the body), and vulnerable to toxins.
2) tubular damage may tigger vasoconstrictoin of afferent arteiroels, exacerbates problem
3) damage fluid may leak into interstitium

NOT the glomeruli, but the tubules and interstitium are invaded by inflammatory cells like crazy (these cells in tubule with halos around them)

IgA nephropathy

in allergic intersitital nephritis

occurs w/ sulfa, penicillins, diuretics, and NSADIS, and begins a couple weeks after drug exosure. Rapidly rising creatinein and they will get better if they drug is stopped