Renal Pathology Flashcards
collecting duct RCC
desmoplasia
kill in months
most aggressive
membranous gn
spikes and holes
•This basement membrane will light up in silver stain and look like a spike in between the immune complex.
Light micrograph showing a glomerulus with segmental sclerosis and collapsed capillaries. A small hyaline deposit is present (H&E stain, original magnification x400).
Hyalinosis
- [Lower right picture.] This is the hyalinosis that can occur [circled].
- These are sort of a glassy appearance to a segment of the glomerulus, and it’s plasma proteins that would normally get bounced back from the podocyte that are going to now accumulate in this area where podocytes are no longer.
- That’s hyalinosis.
cycle of FSGS
- reductions in renal mass
- hypertension and glomerular hypertrophy
- hyperplasia and injury
- FSGS continues
cycle
arteries in bening nephrosclerosis
small and medium thicken in intima nad narrow
mdeial thickening due to smooth muscle hyperplasia
The GMS stain is showing you the fibrosis. What you see is that normally this would be one thin layer of the endothelium(black arrow). The endothelium [in this picture] is extraordinarily thickened (yellow bracket). It is a reactive phenomenon to the high pressures that are constantly pulsating through this artery. It builds up this thick fibrotic endothelium. Obviously that is not good at perfusing the kidney. So the downstream effect is loss of renal mass.
patho features of drug induced interstitial nephritis
interstitial edema
inflammatory infiltrate
typical of hypersensitivity
maybe granulomatous
myeloma cast nephropathy
light chain proteins are toxic to tubules
bence jones protien compine with urinary glycoprotein (tamm horsfall) and tubular casts obstruct the lumen
can result in inflammatory response
malignant nephrosclerosis
from malignant hypeertension
associated with retinal heorrhages, exudates, papilledema
blow out cap due to P@
reatment for high grade papillary tumors
local resection and topical immunotherapy (with BCG)
neothrophilic tubulitis
acute pyelonephritis
global lesion
the entire glomerular tuft of a lesion is effected
unilateral obstruction
may remain silent for long period - 3 weeks for irreversible damage if complete
What does PAS stain
glycoproteins
mucin
tubular injury in medulla
mostly hypoxic
myeloma cast nephropathy
obstruction of tubules by cast material with monoclonal light chains and subsequent injury to the epithelial cells and inflammation due to excretion of normal proteins in the form of Ig components
staging of bladder cancer
crescents
•Cellular crescent are comprised mainly of proliferated epithelial cells and macrophages, fibrin and necrotic debris; this collection of cells is adherent to Bowman’s capsule and in some cases may assume the shape of a crescent (hence the name), but may also extend around the entire circumference of the glomerulus.
drug induced acute interstitial nephritis
consequence of allergic immuno reactions to drugs
drugs may be filtered and reabsorbed via the renal tubules or may arrive via peritubular cappilaries
if drug binds to intestitial protein and form a complex which is presented to T cells to initate an immune response - amplified by cytokines
days to weeks after exposure
chromobobe rcc
areas of clear and of granularity
goodpasture’s syndrome
anti-GBM GN
acute nephritic syndrome w rapid progression
auto abs for non collagenous domain of type IV collagen - linear IgG deposits along capillary loops - activate compliment and inflammatory cells
crescents
molecular basis of low grade urothelial carcinoma
FGFR3
grading of urothelial tumors
urothelial papilloma
urothelial neoplasm of low malignant potential
papillary urothelial carcinoma - low grade
papillary urothelial carcinoma - high grade
interstitial cystitis
persistent painful chronic cystitis in women
chronic ulcers
eitology unknown
histo of MGN
characterized by IgG and C3 granular deposits in the subepithelial region
thick GMB and subepithelal electron dense deposits
idiopathic (phospholipase A2 receptor Abs) or secondary
spikes and holes
arteries and arterioles in malignant HTN
fibironid necrosis or mucoid intimal hyperplasia/onion skinning
We will see fibrinoid necrosis of the large vessels and mucoid onion skinning of the smaller vessels. So this is the reaction of the capillary and arterioles to the high pressures. They try to become very edematous and they get this fibrobastic proliferation. If they can’t handle it, they’ll rupture and you’ll get the petechiae. But we really don’t see the glomerulosclerosis with the malignant hypertension if it happens in a patient without preexisting kidney disease.
xanthogranulomatous pyelonephritis
mass forming inflammatory condition
foamy histiocytes - yellow grey tissue around calyces and pelvis
occaisional multinucleated giant cells and inflammatory cells
secondary hypertension
due to specific causes
renal parenchymal disease
renal artery stenosis
tumors secreting catecholamines
certain drugs
definition of chronic renal failure
azotemia –> uremia progressing for months to years
usually from tubulo-interstital damage
morphology of bladder cancer
80% are sueperficial and non invasive
20% are more invasive
Light micrograph showing a glomerulus with segmental sclerosis and collapsed capillaries (H&E stain, original magnification x400).
segmental lesion
a portion of a glomerulus is effected
acute tubular necrosis
loss of tubular epithelial function and integrigtydue to either ischemic or toxic insult
acute renal failure
oliguria/polyuria
nausea and vomiting
flank pain
cresecents
not specific for a given disease but tend to indicate severe glomerular injury and rupture of GBM
suggest disease is severe - will progress quickly to irreversible scarring fast (Rapidly Progressive Glomerulonephritis - RPGN)
renal cell carcinoma
4 types: clear cell, papillary, chromophone, collecting duct
glomeruli in benign nephrosclerosis
increase in globally sclerotic glomeruli (mostly superficial)
normal have more cellularity but also some foolding and collapse of capillaries (periglomerular fibrosis)
- Basically you lose glomeruli
- Your glomerulus becomes fibrotic.
- Its associated tubules becomes fibrotic.
- Eventually, you just step wise lose glomeruli.
low grade urothelial carcinoma - not mitotic activity
layers
lupus histology
can be any:
focal prolif gn (part)
diffuse prolif gn (all expand to fill bowmans)
membranous gn
sclerosing gn
**all proliferative are subENDO and subEPI deposits and WIRE LOOP - looks like thick bending wire, hypercellular, mesangial deposits
hypercellularity
proliferation of mesangium
infiltration of inflammatory cells or crescents (fibrin)
papillary RCC - lined by small cuboidal cells
- Here is a glomerulus (black circle), tubule (black arrow)
- You start to see a widening of the interstitium (point around area of blue arrow)
- These tubules are not organized very well (tubules around black arrow). There is a widening between the tubules.
- Inflammatory cells sit in interstitial space (cell blue arrow is on).
If there is information in the interstitium, It can easily spill into the tubules or vice versa
risk factors for bladder cancer
male, age
cigarettes
chem exposure
analgesic
schistosomiasis
drugs
minimal change
foot process effacement
condensation of the actin-based cytoskeleton against the sole of the foot process
acute pyelonephritis
inflammation of the interstitium and tubules secondary to an infectious process (usually ascending from the lower urinary tract)
infection and inflammation involves the pelvis and calyces of the kidney with secondary involvement of the cortex
infection of the kidney can lead to interstitial nephritis
lab findings in acute pyelonephritis
white cells and bacteria in the urine
elevated WWBC count
increase in creatinine and BUN
increased kidney size
what does trichrome stain
fibrosis (collagen)
ischemic tubular injury
disruption of arterial supply or decrease in effective circulating volume (hemmorrhage, shock, sepsis)
reoxygenation may lead to reperfusion injury
nephrotoxic acute tubular injury path
renal tubular epithelium may show greater structural injury with frant necrosis of the epithelial cells
glomerulonephritis - diabetic
•Some of these exudated proteins can actually deposit in the capsule itself. [green arrow] It is another clue that the patient is diabetic.
4 types of kidney stones
- Ca
- Mg
- uric acid
- cystine
chromophone RCC
stain more darkly than cells in clear cells RCC
numerous chromosomal deletions
good prognosis
mech of toxic tubular injury
interference with oxidative metabolism gen of free radicals and cell damage
malignant hyptertension
aggressive
scarring of kidneys with rapid and irreversible loss of renal function
like rapid progressive glomerulonephritis
malignant hypertension can be lethal!
visual disturbances,headache, nausea, vomiting, neuro symptoms
treatment for low grade papillary tumors
local resection
cytology to detect recurrence
histo features of post-infectious GN
diffuse glomerular hypercellularity - due to proliferation of endothelial and mesangial cells and infiltration of neutrophils and monocytes –> occlusion of capillaries
too ceppular - can’t make out loops
breakdown BM
Light micrograph of a glomerulus with rather extensive sclerosis involving the majority of the glomerular lobules. Note adhesion of involved lobules to Bowman’s capsule (PAS stain, original magnification x400).
- So what we see here is glomerular capillary loops [arrow], endothelial cells, a podocyte.
- This half [black circled] of the glomerulus actually looks pretty good.
- This half [uncircled] does not.
- The capillary loops, you can’t really make them out, and it seems that there might be some expansion of the mesangium here.
- This is a segmental sclerotic portion of the glomerulus.
- It’s focal because I’ll tell you that less than 50% of the glomeruli are affected, and it’s segmental because only a portion of this entire glomerulus is affected.
- This is what a crescent looks like.
- So this is the glomerulus right now (1)
- This is the capsule (2)
- And here’s the crescent (3)
- Basically it’s not really in contact with the podocyte, but what you can see is that there’s fibroblasts (sort of spindly and roundish cells), there’s some karyorrhectic debris- what does that mean? Karyorrhectic debris just means that cells are being destroyed and blown apart, and there’s little dots of debris in there.
- There may be also some neutrophils
- And it forms exactly that (a crescent); it sort of envelops the glomerulus in the fashion of a crescent.
- This picture is one of rapidly progressive glomerulonephritis- extremely severe glomerulonephritis. These are the patients that do very very poorly.
diabetic glomerulonephritis
- What we see on staining is you have this exudation of proteins and abnormal glycosylation of proteins that get trapped in the mesangium. The mesangium becomes sclerotic and we demonstrate that with a PAS stain.
- These are called Kimmelsteil Wilson nodules. The capillary loops actually look pretty good [green arrows].
- This is the mesangium [blue oval] and you have this nodular accumulation of exudated proteins within the mesangium that form these nodules.
low grade papillary urotehlial carcinoma
papilloma
hyaline arteriosclerisis
characteristic change in benign nephrosclerosis
arterioles thicken and narrow
comprised of hyaline - acellular, glassy eosinophic materia
plasma proteins leak across damaged endothelium and ECM proteins made by smooth muscle cells
papillary RCC
tubular and interstitium changes in benign nephrosclerosis
varying degrees of tubular atrophy and accompanying interstitial fibrosis
inflammatory infiltrates (non specific)
atrophic tubules look small and flat
The interstitium becomes fibrotic. What will happen is, let’s just say taken in isolation you have one sclerotic glomerulus. You have no capillary loops there. Its downstream tubules will be lost. Initially you get an inflammatory infiltrate as a sort of reaction to the dying process of the glomerulus. Over time that inflammation goes away.
podocyte injury in minimal change
altered phenotype - no change in number
renal ademonas
small papillary tumors - BENIGN
foudn often in autopsy - incidental finding (small)
definiton of FSGS
focal segemental glomerulosclerosis
segmental solidifcation of the tuft
hyalinosis and foam cells
proteins sit in the scar tissue
drug induced interstitial nephritis
- This is what it looks like under the microscope.
- The tubule here (blue circle)
- The interstitium (everything else) is widened by lymphocytes and eosinophil
- The combination of lymphocytes and eosinophils would suggest that it is drug induced
- And that is what that looks like here
- If you compare it to the normal kidney (left)
- Has polarity: nucleus is on the bottom
- Has basement membrane
- ATN kidney (right)
- These cells almost look squamoid (black arrow above acute tubular injury). They look really flat. They are progenitor cells trying to re-epithelialize the tubule.
- This is the recovery phase of ATN
- In that process you still get interstitial edema.
- Interstitial edema is not going to help with areas of countercurrent mechanism or something like that.
- You have these big large spaces and water in a place where it is not suppose to be. That will also make it more difficult for these patients to recover
- So at all phases of ATN you can have significant renal injury and it can be difficult to recover.
- This tubule is recovering better (T). You can see the brush border is coming back.
malakoplakia
plaque like deposits in mucosa of bladder due to deposits of overloaded macrophages
loss of degradative funciton of macrophages
benign mass forming lesions - defective macrophage function that bllocks lysosomal degradation of engulfed bacteria - fillin up cytoplasm w undigested debris
foamy macrooages (yellow color)
chronic pyelonephritis
scarring
renall scarring with depormed calyx
thyroidization of tubules in cortex - filled w scars
post infectious GN - HUMPS
- The curious part about post-streptococcal is that the IC being produced seem to be cationic and they give you these electron dense deposits in the subepithelial space, but only rare deposits in the subepithelial space. So you don’t get full-on nephrotic syndrome.
- You have both a subepithelial process and a subendothelial process. So these patients can have a nephritic-nephrotic picture. You see nephritic b/c a lot of these endothelial space is trapping all those IC being produced and you have some other cationic IC that are then going across to the podocytes and we are leaking some protein in those IC. So it’s both that’s happening.
- The complement being produced at the subendothelial level and the protein being put in the urine at the subepithelial level. So it is both.
- The curious thing about this is that they are just rare deposits – so they are called humps in the subepithelial space. See the cartoon in the upper right.
ATN under microscope
- So this is a vessel (V)
- These are capillaries (black arrow)
- This is a tubule that looks okay (T).
- The nuclei is still close to the basement membrane.
- Cells still have polarity.
- Still see nuclei in the cells
- This cell is undergoing apoptosis (green arrow):
- Nucleus is condensing
- Cytoplasm turning very dark
- Cells undergoing necrosis (blue arrow)
- Just have a ghost outline of the nucleus
- It is detached from the basement membrane and sitting in the tubule. So all of these cells just snuff off into the tubule
- This is the classic picture of ATN. You lose that nice brush border that you typically have (black circle). It can get bubbly and disorganized.
- This is obviously a spectrum. It may start off looking like this (black circle). And end up looking like this (blue arrow) or this (yellow arrow). This (blue circle) is maybe before this picture (black circle). You still have a little bit of a brush border here and the cells are still polarized but the cytoplasm is starting to get really vacuolated.
- And these are dead (red circle)
You can re-epithelialize the tubules (red arrow) or else none of this would be reversible
proliferative GN (lupus)
- The first one is focal, proliferative glomerulonephritis.
- Let’s just say this person as anti-double stranded DNA circulating antibodies, and had this clinical picture that I showed you in the beginning, and they do a kidney biopsy and let’s say 50% of the glomeruli are affected, and what we see under the microscope is a segmentally hypercellular glomerulus.
- So this portion of the glomerulus doesn’t look all that bad (1), whereas in this portion (2), what we see is this karyorrhectic debris, pieces of cells, fibrin- this pink stuff (3)- in the bowman’s space, we see here’s maybe a podocyte (4), a macrophage (5) here, and a loop of a capillary that’s got a neutrophil in it (6).
- We can’t really follow the normal contour of the basement membrane on this side; it just looks like a mess. There’s just too many cells here (7).
So this is a focal proliferative glomerulonephritis. Something is happening at the level of the endothelium; that’s why we’re spilling all these cells into the urine
high grade papillary urothelial carcinoma cells
cells that shed into urine
nuceii variation
Goodpasture’s IF
•This is probably the only picture that you would see on your USMLE; it almost looks like, at night, one of those neon signs like at a diner or something like that. It has that appearance to it due to those anti-GBM antibodies lining up along that basement membrane and tracing it pretty much exactly, so it has this very nice, linear immunofluorescent pattern.
membranous GN
diffusely thick GBM
spikes and holes on silver stain
•This basement membrane will light up in silver stain and look like a spike in between the immune complex.
chronic interstitial nephritis
- This is a PAS stain. Know this is PAS because basement membrane which is hypercollagen is staining pink (where arrows above “tubular” is pointing).
- I have lots of this light pink in the interstitium when I shouldn’t have anything (where arrows above “intersitial fibrosis” is pointing). This light pink indicates that there is collagen deposition.
histology of collapsing glomerulopathy
HIV!! reactive
- For whatever reason, when the HIV virus infects components of the mesangial cells and the glomerulus, it gives this pattern of injury.
- What will happen is either a segment or the entire glomerular capillary tufts will just close off and collapse down.
- This basement membrane stain [top right] is showing you that. There’s no holes like we saw before in the normal glomerulus, those nice capillary loops. There’s nothing here, just sort of this blacked-out charcoal look.
- The whole glomerular tuft is collapsed and you have this proliferation of podocytes all along the top of it.
- This is a reactive phenomenon seen in HIV patients, thought to be due to the infection of these cells by the virus.
- [Left picture] Once the glomerulus is dead [lower right of left pic] the tubules will atrophy and in this atrophic process they’ll dilate out, and you’ll see this cystic-like spaces associated with the glomerulus that’s serving these tubules. [red globs]
- This is a consistent association with HIV and AIDS. These patients tend to get FSGS and/or collapsing glomerulopathy if they have involvement of their kidneys.
•
podocyte injury in FSGS
engagement of apoptotic pathways –> podocytopenia
podocyte injury in CG
de-differentiation –> high proliferation
fibrumuscular dysplasia of the renal artery
heterogeneous group of lesions characterized by fibrous or fibromuscular thickening of the vessel walls and thickening of the lumen *usually media!!!)
The fibromuscular dysplasia would look like this. It is sort of like a mucoid thickening of the media.
The intima is not normal looking either. You can have these pouches and cyst like space that develop. It just looks very abnormal and dysplastic. These things can be stenotic. If they are stenotic, they will impede blood flow.
Or a person could be born with a very small renal artery that looks normal under the microscope but the caliber of the size is just very small.
