Kidney Systemic Disease II Flashcards
sickle cell nephropathy - where in the kidney does sickling happen?
inner medulla
What 3 factors of the inner medulla make it a prime area (the prefect storm) to cause polymerization of deoxygenated Hgb S and sickling of erythrocytes?
1) relative hypoxia
2) acidosis
3) hyperosmolarity
what pathologic, structural functional change does sickle cell nephropathy cause over time in the kdiney?
considerable decrease in the cortical vasculature and the vasa recta are virtually absent
pt comes in with microalbuminuria, hyposthenuria (decrease of concentrating ability) - your differential could include nephrogenic DI and what else
sickle cell -
sickle cell - what key finding do you see in early childhood into young adulthood with regards to the kidney?
How does this manifest in clinical findings?
1) increased GFR in early childhood, young adulthood - hyperfiltration
2) you will see a lower creatinine than expected (in plasma)
sickle cell - what is an impt histo feature you see on biopsy
papillary infarcts / necrosis
sickle cell - what other pathological processes will be present seen on biopsy of the later stages
interstitial inflammation, edema, tubular atrophy and fibrosis
what does sickle cell nephropathy common progress to as end stage
ESRD – FSGS w/ glomerular enlargement
sickle cell - if he has a picture of a LM kidney biopsy slide, what general things would you see
a lot of red blood cell occlusions – due to all the sickling, you will see a lot of red, gumming up the glomeruli and peritubular capillaries
glomerulomegaly and mesangial expansion; tubular epithelial hemosiderin acumulation; interstitial fibrosis and vascular sclerosis
sickle cell nephropathy
amyloidosis - misfolded proteins - what do they fold into
beta pleated sheets
amyloidosis - where do deposits get put first
blood vessel walls
amyloidosis - what causes organ failure
deposits get into the interstitium, stuff squeezes the cells to death
AL (primary) amyloid - what is the abnormal protein
immunoglobulin light chain (usually lambda)
AL amyloid - what is a feature of the disease underlying
monoclonal *** gammopathy
I think this will be on test
what do we call light chains that get into the urine
Bence Jones proteins
pt comes in with either Rheumatoid Arthritis or Inflammatory Bowel Disease - what are you thinking (amyloid)
AA - secondary reactive amyloid
RA and IBD - 2 most common systemic diseases giving rise to this reactive type amyloid
AA - secondary amyloidosis - what is the cause in general
a systemic chronic inflammatory disease
what molecule needs to be present in order to have amyloidosis formation (i.e. fibril formation)
AEF - amyloid enhancing factor
without this, will not have amyloidosis - just having circulating amyloid is not enough
amyloid kidney - what kind of glomerulopathy is seen? what will you see on urinalysis
1) nonproliferative, noninflammatory
2) proteinuria, NOT hematuria
w/ renal amyloidosis, what is the size of the kidneys
enlarged
what are the 2 pathological processes in the kidneys that are end result of amyloidosis (bad news bears)
tubular atrophy and interstitial fibrosis
what stain do you use for amyloidosis?
congo red
what is a setback with congo red ?
can get false negatives
does not always appear very red
(can look tan, peachy, salmon, some may even say taupe)
congo red can never tell you what type of amyloid is present. what test can?
immunoperoxidase stain
what is a setback of immunoperoxidase stain
false positives
do you see HTN w/ AL amyloidosis
no
note that amyloidosis AL is associated with GI symptoms
GI dysmotility, malabsorption, hemorrhage or obstruction
what is the treatment for AL? what is the prognosis?
1) melphalan and dexamethasone (if pt younger than 50, can do autologous stem cell transplant)
2) shitty - median survival 10 months
what is a third cause of AA
ankylosing spondlyitis
what abnormal protein si involved with AA amyloid?
what is it produced in response to?
1) serum amyloid A protein
2) acute phase reactant produced by liver in response to IL-1 and IL-6
what is a new treatment option for AA
eprodisate - limits deposition of amyloid A fibrils by interfering w/ their interaction w/ tissue glycosaminoglycans
what is most common cause of death in AA
death usually from infection or dialysis related complication - b/c most AA pts end up on dialysis in end
what type of amyloidosis occurs with long term hemodialysis
Amyloid beta2m
this is beta 2 microglobulin
where does amyloid beta2m prefer to deposit
synovium, joints, and tendon sheaths
this is unique and he kind of emphasized it
amyloidosis type that presents with heart failure and arrhythmia
amyloid TTR - transthyretin
what is the function of transthyretin
transporter protein for thyroxine and retinol (notice how the name “transthyretin” actually describes its function)
what is another name for light chain deposition disease
nonamyloid monoclonal immunoglobulin deposition disease (MIDD)
light chain deposition disease (MIDD) - what underlying disease
multiple myeloma
sicca syndrome
1) what is it?
2) if you see this in a question stem, what disease are you thinking?
1) dry eyes, dry mouth
2) light chain deposition disease (MIDD)
for light chain disease, what other disease does the histo resemble?
diabetic nephropathy
nodular glomerulosclerosis
expansion of mesangial matrix
what is unique about the protein assocaited with light chain disease
kappa is more common than lambda (diff from AL)
light chain disease on EM - where does it deposit and what is the buzz word for what it looks like
1) endothelial cell side (subendothelial)
2) silt
if you see the combination of “heavy proteinuria” and “minimal swelling” what are you thinking
HIV associated nephropathy (HIVAN)
HIVAN - what is the classical glomerulopathy
collapsing form of focal segmental glomerulosclerosis
what is the buzz word finding on histo for HIVAN
microcystic tubular dilatation
what is a key susceptibility allele associated with HIVAN
APOL1
palpable purpura, arthralgia, elevated serum RF in a Hep C patient - what is the diagnosis
mixed cryoglobulinemia type II
what is the pathogenesis of cryoglobulinemia
deposition of immune complexes on endothelial surface, activation of complement and eliciting vascular inflammation
what will you see on urinalysis of cryo? (think inflammation)
hematuria
cryo - what kind of disease picture of the glomerulus seen on renal biopsy
MPGN
purpura, arthralgia, and weakness - what is this and what disease is it associated with
Meltzer’s triad - associated with cryo
what kind of immunoglobulin is RF
IgM – binds IgG
what is seen on EM with amyloidosis
randomly oriented fibrils
what is a key diagnostic feature of light chain disease? (recall, it is not true amyloidosis)
congo red negative
cryo - what is contained in the immune complexes
RF, IgG, HCV RNA, and complement
