Renal - Path Flashcards
1
Q
1) What pt population is anti-GBM significantly more common in (men vs women, old vs young, race),
2) and why
A
1) young white males
2) men have a thicker GBM than women
2
Q
what percentage of the capillary surface may correspond to fenestrations?
A
50%
3
Q
w/ regards to the glomerular capillaries, what does this lack of a continuous cytoplasmic barrier facilitate? essentially, what do the fenestrations allow through and the significance?
A
fenestrations allow filtration and accessibility of macromolecules (including antibodies**) to GBM
antibodies - in diseases
4
Q
Describe the arrangement of the cell process (pedicels) of the podocytes wrapping around the glomerular capillary
A
interdigitating - the key is that each adjacent pedicel belongs to a different cell
5
Q
nephrotic syndrome –> “effacement” of foot processes of podocytes –> what is nichols’ “in reality” description of effacement
A
retraction of foot processes and loss of slit pore diaphragm
6
Q
what is the result of effacement of the foot processes? (on a functional mico anatomy level, not the pathology)
A
long segments of capillary that are invested by the cytoplasm of a single podocyte
7
Q
what else happens in addition to effacement of podocyte foot processes that actually allows the plasma proteins to leak?
A
there is detachment of foot processes from the basement membrane –> allowing the leak
8
Q
what is the structure of the glomerular basement membrane, i.e. how it differs from most basement membranes? what does it consist of?
A
1) trilaminar structure
2) a) lamina lucida (or rara) (closer to endothelium)
b) lamina densa - double the usual thickness, double the thickness of lamina rara
c) lamina rara externa (closer to epithelial cells)
9
Q
what does the structure of the glomerular basement membrane represent?
A
embyological fusion, at the level of the lamina densa, of 2 basement membranes - endothelial and epithelial
10
Q
1) what constitutes the slit pore diaphragm?
2) their functions
A
1) proteins secreted by podocytes
2) a) cadherin and FAT - serve to bind adjacent pedicels
b) nephrin and podocin - play role in filtration
11
Q
mutations in what slit pore diaphragm proteins result in congenital nephrotic syndromes? and why?
A
1) mutations in nephrin and podocin genes
2) loss of large amounts of protein in urine from defective slit pore diaphragm
12
Q
major component of GBM
A
type IV collagen
13
Q
3 other major components of GBM and their functions
A
1) perlecan - highly charged proteoglycan containing heparan sulfate –> imparts most of the charge properties of basement membranes (like blocking albumin)
2) entactin - glycoprotein w/ Ca binding properties
3) laminin - family of complex glycoproteins formed by 3 diff chains - impt in maintaining structure of GBM
14
Q
what constitutes a collagen molecule (type IV)
A
3 alpha chains form a collagen molecule – there are 6 numbered alpha chains of type IV collagen - variability in composition of individual molecules - variability in basement membranes
15
Q
most of the alpha chains are in the characteristic helical conformation, except for what part of a collagen molecule
A
the non-collagenous domain - a non-helical globular domain
16
Q
Goodpasture syndrome
1) antibodies against what inciting antigen?
2) clinical signs/symptoms
A
1) antibodies against an epitope in the NC1 domain of the alpha3 (IV) chain
2) causes glomerulpnephritis w/ hematuria and pulmonary hemorrhage w/ hemoptysis
(Goodpasture is when they have both)
17
Q
Mesangial cells (the mesenchymal cells of the kidney) have what properties
A
phagocytic and contractile properties
they phagocytose antibodies and Ag-Ab complexes
18
Q
the 2 most comon types of glomerular diseases are
A
1) diabetic
2) immune-mediated
a) antibodies
b) immune complexes
19
Q
immune complexes leading to glomerular disease can get there and cause problems by what 2 ways
A
1) deposited from circulation
2) immune complex formation in situ (ie forms in the glomerulus)
20
Q
in situ antibodies causing glomerular disease can be against what 2 types of antigens (broad categories)
A
1) intrinsic (fixed) antigens
2) “planted” antigens originally from the bloodstream
21
Q
large circulating immune complexes typically deposit where and why
A
1) subendothelial
2) can pass through fenestrations, but cannt pass through GBM, get stuck there
22
Q
circulating antibodies against the GBM
1) deposit where
2) in what pattern
3) what disease do you see this in
A
1) subendothelial
2) linear pattern all along the GBM
3) Goodpasture syndrome
23
Q
what is the treatment for anti-GBM antibodies? i.e. how do you remove them
A
plasmapheresis - anti-GBM antibodies typically circulate before being deposited - tx for Goodpasture
24
Q
circulating antibodies against antigens in the cell membrane of podocytes
1) deposit where
2) what pathology do you see this in
A
1) deposit outside the GBM (at the level of the podocytes)
2) membranous nephropathy
25
post-streptococcal glomerulonephritis is an immune complex disease w/ antibodies against what?
streptococcal pyogenic exotoxin B
26
post-streptococcal glomerulonephritis - how do the immune complexes form?
immune complexes form partly in situ with antigens "planted" in the GBM from the circulation
27
post-streptococcal glomerulonephritis - what do you see on EM
subepithelial "humps"
28
post-streptococcal glomerulonephritis - what do you see on immunofluorescence
granular deposits - more granular than the subendothelial deposits of lupus
29
there is 1 metabolic disease of the glomerulus
1) what is it
2) what percentage of glomerular injury does it account for
1) diabetic glomerular injury
| 2) 50%
30
what is the first step in the etiology of diabetic glomerular injury
hyperglycemia causes non-enzymatic glycosylation of proteins in blood and in GBM
31
after glycosylation of plasma proteins and GBM proteins, what is the next step in the etiology of diabetic glomerular injury
some of the glycosylated plasma proteins get trapped in the GBM along w/ the glycosylated native proteins --> stims the production of new GBM protein
32
what is the eventual result of diabetic glomerular injury
thickened GBM - distorted by glycosylated proteins
33
diabetic glom injury - what is AGE (it is an acronym)
advanced glycation end-products - some of the glycosylated proteins are further metabolized, forming AGE
34
In addition to AGE what other bad fuckers are involved in fucking up your glomeruli in diabetic glomerular injury (3)
1) advanced oxidation protein products [AOPP],
2) the RAAS,
3) TGF-beta
35
diabetic glomerular injury - AOPP, RAAS, TGF-beta, AGE - what do they activate
activate/induce NADPH oxidase - produces ROS
36
diabetic glomerular injury - AOPP, RAAS, TGF-beta, AGE - activate/induce NADPH oxidase producing ROS - what does this cause (3)
1) mesangial matrix production
2) podocyte injury and apoptois
3) proteinuria
37
hemodynamic glomerular injury
1) what is the cause
2) etiology
1) HTN- hydrostatic pressure higher in glomerular capillaries than normal
2) instead of just driving filtration, it injures the glomerulus? (his notes literally say "injures them") fucking good wording
38
hypertensive nephropathy - hemodynamic glomerular injury - the supranormal glomerular capillary pressure causes what pathologic results in the glomerulus
1) GBM thickening
2) mesnagial cell hypertrophy and hyperplasia
3) mesangial matrix production
39
HTN causes
1) what pathologic process
2) where (site selectivity)
1) hyaline sclerosis of arterioles
| 2) afferent arterioles but not efferent arterioles
40
HTN --> hyaline arteriolosclerosis of afferent arteriole --> causes what disease process in the glomerulus
gradual narrowing of the afferent arteriole lumen --> ischemic atrophy of the glomerulus
41
HTN - eventually causes what (along lines of hyaline sclerosis) and what is this term for end-stage hypertensive nephropathy
1) globally sclerotic glomeruli
| 2) ARTERIONEPHROSCLEROSIS
42
what population is arterionephrosclerosis more common in and why
1) African Americans - 8x more common
2) trypanosoma brucei rhodesiinse - (african sleeping sickness) - mutations in the gene for apolipoprotein L1 - does some shit that confers resistance to this disease
43
Malignant HTN - what population is it more common in and what is the typical epidemiology
african americans - BP > 200/120, causes HA, vomiting, proteinuria, hematuria, scotomas ("spots before the eyes") and renal failure --> youngish black males around age 40
44
Malignant HTN produces what disease process of the arterioles and what does this lead to in the glomeruli
fibrinoid necrosis of the arterioles --> leads to necrosis of glomeruli
45
what other buzz word process does malignant HTN cause in small arteries
"onion skinning" - proliferation of intimal cells in small arteris - hyperplastic arterosclerosis
46
how specific are hyperplastic arteriosclerosis and arterial fibrinoid necrosis for malignant HTN
not very
47
small arteries and arerioles damaged by malignant HTN can do what, causing what appearance of the kidney
burst - cause "flea-bitten" kidney
48
Malignant HTN is what (big red slide, do not miss dx)
MEDICAL EMERGENCY - it can be fatal - 5 yr survival is only 50%
49
what is the most common cause of death in malignant HTN
renal disease - 90%
50
it is unique to kidney biopsies to require what 3 types of microscopy
1) light
2) immunofluorescence
3) electron
51
Diffuse
involving all or most of the glomeruli
52
focal
involving some but not most of the glomeruli
53
Global
involving the whole glomerulus
54
Segmental
involving only part of the glomerulus
55
Proliferative
increased cells - proliferating native cells, but also infiltrating inflammatory cells
56
membranous
increased GBM - w/out increased cells
57
MPGN
membranoproliferative (glomerulonephritis) combination
58
crescentric (glomerulonephritis)
disease involving Bowman space with proliferating parietal cells and infiltrating macrophages
59
necrotizing w/ organizing
has some repair processes going on
60
"pauci-immune"
ANCA antibodies involved in crescentic glomerulonephritis but these antibodies are not visible on immunofluorescnce or electron microscopy of glomeruli
61
glomerulosclerois
fibrous scar replacing glomerulus
62
"acute necrotizing crescentic glomerulonephritis"
infiltration of immune cells, mostly macrophages, less commonly neutrophils, causing cell death quickly. Crescentic = Bowman's space - inflammation of - parietal epithelial cells proliferate into the open space
63
crescentic is...
literally. the worst
64
"focal segmental glomerulosclerosis"
scarring of parts of a few of the glomeruli - more advanced than acute
65
prognosis of crescentic glomerulonephritis
bad
66
Post-infectious glomerulonephritis (PIGN) - location of deposits
1) early in the disease
2) later in the disease
3) the significance
1) sub-endothelial
2) sub-epithelial
3) most pts don't get biopsied until later in the disease course - when deposits are sub-epithelial
67
for immune complex deposition diseases of glomerulus, what other site of deposition is usually associated with subendothelial deposition
mesangium
68
what 2 diseases are characterized by subepithelial deposits
1) post-infectious GN
| 2) membranous nephropathy
69
what is a characteristic feature of the antigen associated with post infectious GN
it is planted there - immune complex forms in situ
70
what is a characteristic feature of the antigen associated with membranous nephropathy? what pattern of deposition does it lead to?
1) antigen is intrinsic to the podocytes
| 2) deposits are continuous along the subepithelial space
71
anti-GBM disease
Goodpasture
72
mesangial deposits typical of which pathology
IgA nephropathy
73
what is the pattern associated with Anti-GBM ab binding
Abs bind in a linear fashion
74
(in general, as a clinician) when you see a pt come in w/ edema, what 3 pathologies should you think of?
1) CHF
2) cirrhosis
3) proteinuria = nephrotic syndrome
75
what are the 3 purposes/ indications for kidney biopsy
1) Dx
2) prognosis
3) Guide therapy
"guiding therapy or elucidating a failure to respond to therapy is an indication for biopsy"
76
recall the 3 slide preparations that are unique to kidney biopsy (no other tissue sample requires all three of these)
1) light microscopy
2) immunofluorescence
3) electron microscopy
77
what are some of the requirements of all kidney biopsies
1) each slide prep requires a different tissue processing
2) all require rapid placement into appropriate preservative
3) all require planning and coordination to have the right reagents on hand and the right transport carried out
i.e. do not do them at 5 PM on a Friday afternoon
78
what are the absolute and relative contraindications to kidney biopsy? (5)
```
absolute
1) bleeding diathesis
2) uncontrolled HTN
relative
3) single kidney
4) high pressure hydronephrosis
5) adult polycystic kidney disease
```
79
buzz word "foot process effacement"
| seen on EM
minimal change disease (MCD)
80
buzz word "spike and dome"
| seen on EM
membranous nephropathy
81
buzz word "subepithelial humps"
| seen on EM
post-infectious glomerulonephritis
82
what is Larry's new, favorite word instead of "effacement"
"fusion" - fusion of foot processes
83
buzz word "tram tracks"
membranoproliferative glomerulonephritis
84
buzz word "basketweave"
alport syndrome
85
buzz word "wire loops"
lupus nephritis
86
buzz word "onion-skin"
HTN nephropathy or scleroderma
87
what particles are the most easily filtered through the glomerular barrier?
small size, cationic particles
88
what is the size barrier? (2)
lamina densa of GBM and the slit diaphragms
89
what is the charge barrier?
lamina rara interna, and apparently the fenestrated capillary endothelium
90
dysfunction of alpha-Actinin 4 causes what
AD FSGS
91
dysfunction of podocin
AR steroid resistant FSGS
92
dysfunction of TRPC6
gain of fxn mutation --> AD FSGS
93
dysfunction of NEPH1
AR Finnish type, resembles MCD
94
what example of a low molecular weight protein did we mention as one that has almost completely unrestricted filtration through GBM
beta2 microglobulin
95
what happens to the protein that does get filtered and arrives in the tubular lumen?
almost all gets reabsorbed in the PCT, only a small amt gets excreted in urine
96
what is the mechanism of protein reabsorption in the PT
endocytosis - by the epithelial cells in the PT
97
amount of protein that reaches Bowman's space is a direct function of what? and what clinical significance does this have?
1) intraglomerular pressure
| 2) this is a target for anti-HTN meds --> a means to reduce proteinuria
98
compare the filtration of both small and large size proteins in normal kidney function and NS
1) large proteins are filtered more easily in NS
2) small proteins are filtered more easily in nml GBM function, decreased filtration in NS - result of less surface area available for filtration w/ NS
99
what is the lowest amount of albumin that can be picked up by a urine dipstick? what is the sensitivity of the dipstick?
300 mg/day
100
what is the normal amt of albumin excreted daily
30 mg/day
101
how do you measure albumin levels of between 30-300 mg/day
spot ratio test - find the ratio of urine albumin/creatinine OR can use the microalbuminuria
102
which test is preferred between the spot ratio albumin/creatinine or the microalbuminuria for detecting albumin in urine 30-300 mg/day
the spot ratio test - corresponds fairly accurately to the proteins collected in a 24 hr urine collection - means we don't have to run 24 hr collections much anymore
103
what is a normal 24-hr urine collection level of albumin
less than 150 mg
104
what is the normal spot urine creatinine ratio
less than 0.15
105
what is the nephrotic range of 24-hr urine collection
greater than 3.5 grams
106
what is the nephrotic range for spot urine protein creatinine ratio
greater than 3.5
107
For minimal change disease, what is the pathological appearance on light microscopy?
normal
108
Minimal Change Disease, what 2 main pathologic appearances are we looking for on Electron Microscopy?
1) effacement/fusion of foot processes
| 2) detachment of foot processes
109
Why is it relatively easy to miss the Dx of FSGS? and if so, what will you think/treat it as/ what will you see?
1) if biopsy misses an area of scarring (b/c it is focal and segmental) then will miss dx
2) MCD - will see poor response to steroid therapy
110
What percentage of pts w/ FSGS develop end stage kidney disease? what is the time frame?
50% of pts w. FSGS develop end-stage kidney disease w/in 10 yrs of diagnosis
111
what is the novel discovery in primary FSGS?
suPAR - soluble urokinase-type plasminogen activator receptor - associated w/ FSGS, permeability facotr released by T cells
112
what does suPAR bind and where?
in the glomerulus, suPAR binds w/ integrin - leads to dysfunction of podocytes
113
what chromosome is the apolipoprotein L1 gene (APOL1) located on?
22
114
what is the most common cause of nephrotic syndrome in african American adults?
FSGS
115
the most common cause of nephrotic syndrome in white adults
membranous nephropathy
116
adhesion of involved segment to Bowman capsule is an important feature of what disease
FSGS
117
which subtype of FSGS has the worst renal survival?
collapsing
118
which subtype of FSGS is more likely to obtain remission (best prognosis)?
Tip
119
What did Larry make a point to say about the Tip variant of FSGS?
it is very focalized and it is on the opposite pole
120
What was Larry's epidemiology example of collapsing FSGS
HIV autopsies from LA county in the 80s (he likes it - probably on test)
121
what is the most common tx for FSGS (initially?)
corticosteroids
122
If a FSGS pt is non responsive to corticosteroids, what is the 2nd line treatment option? What was Larry's point about this tx option?
calcineurin inhibitors (cyclosporine, tacrolimus) - they themselves are nephrotoxic
123
if a pt is 50 yr or older, present w/ membranous nephropathy, what do you need to immediately check them for?
look for tumor as a cause of secondary MN
124
what % of MN spontaneously resolves?
30%
125
what % of MN progresses to renal failure?
40%
126
Since 30% of MN spontaneously resolves, how does this guide our tx?
Rx for MN is selective - only provided for pts who are at high risk for progression to ESRD -i.e. you don't need to treat everyone w/ MN w/ cytotoxic agents
127
for MN, what are the 6 risk factors for loss of renal function?
1) male
2) 10 g/24 h proteinuria
3) HTN
4) Azotemia
5) Tubulointerstital fibrosis
6) glomerulosclerosis
128
for MN - what is our deciding factor for whether to tx w/ supportive measures or w/ disease modifying?
proteinuria
less than 4 gm - supportive
more than 4 gm - disease modifying
129
membranoproliferative glomerulpnephritis can be associated with which type of gammopathy, monoclonal or polyclonal? what will you see on immunofluorsecence
monoclonal gammopathy
immunofluorescence - the Ig will be exclusively kappa or lambda - only one will light up
130
what is the classic appearance of dense deposit disease on EM
dense dark continuous ribbons
131
what is the most common primary glomerulonephritis world wide?
IgA nephropathy
132
what is the tx like for Goodpasture?
aggressive - "kitchen sink" - corticosteroids, plasmapheresis, and cytotoxic agents
133
from Larry - in Anti-GBM disease, in addition to cresecents, what will you see on EM
breaks in the basement membrane
134
young male p/w hematuria and a fmaily hx of renal problems - what is most likely
Alport
135
what is another associated symptom w/ alport
sensorineural hearing loss
136
Alport - "basket weave" - what does this refer to?
the splitting of the lamina densa
137
medium vessel disease - renal infarcts; is this associated with glomerular inflammation and RBC casts? ANCA status?
1) not associated w. glomerular inflammation w/ RBC casts
| 2) ANCA negative (Think PAN)
138
small vessel disease - crescent formation; what do we see in UA? progression of kidney failure? ANCA?
1) active urinary sediment
2) rapid progression of kidney failure
3) ANCA positive
139
pt comes in, mid 60s, ANCA negative, maybe Hep B or C, fatigue, wt loss, weakness, fever, arthralgias - what you thinking?
Polyarteritis nodosa
140
PAN w/ Hep B - what else are you likely to see w/ regards to the kidney
membranous nephropathy
141
PAN w/ Hep C - what are you likely to see w/ the kidney
MPGN
142
PAN - characteristics of vasculitis
segmental transmural necrotizing
143
PAN - what will you see in histo for
1) early in the disease
2) later
1) early = neutrophils
| 2) fibrinoid change, necrosis of vessel wall
144
what is a key physical exam finding for PAN that is also a way to remember the pathology?
palpable subcutaneous nodules - they are thrombosed or severely inflammed aneurysms = "nodosa"
145
What are 2 pathologic processes that can be seen w/ PAN
1) renal infarcts
| 2) arterial aneurysms
146
what is a bad, silent complication of PAN
if an aneurysm in the kidney bursts - retroperitoneal hemorrhage, pt p/w hypotension and syncope
147
Binding of ANCAs to neutrophils results in PMN activation - what does this lead to
increased contact and adhesion w/ ednothelial cells and vascular structures
148
Binding of ANCAs to neutrophils results in PMN activation - adhesion to endothelial cells and vascular structures - what moderates the adhesion (3)
1) Beta-2 integrin
2) Mac-1
3) Fc gamma
149
what is significant about ANCAs in small vessel vasculitis, and how does this relate to treatment
ANCAs are pathogenic - we can treat by plasmapheresis
150
Granulomatosis w/ polyangiitis - what kind of syndrome is it (think about where it all affects)
sinopulmonary renal syndrome
151
Granulomatosis w/ polyangiitis - in addition to the sinus/pharynx and lower respiratory tract symptoms, what else may be seen
fever, wt loss, arthralgias/arthritis mononeuritis multiplex, skin lesions (papules, vesicles, purpura)
152
histo slide - multinucleated giant cells (subtle), pathergic necrosis, blue haze
granulomatosis w/ polyangiitis
| blue haze = nuclear dust from breakdown of polys
153
granulomatosis w/ polyangiitis - what kind of GN
crescentic
154
hemolytic anemia (schistocytes on blood smear), renal dysfunction, thrombocytopenia (due to platelet consumption)
Hemolytic uremic syndrome
| classic clinical triad
155
hemolytic anemia, thrombocytopenia, renal dysfunction + fever and neurologic dysfunction
Thrombotic thrombocytopenic purpura
156
what is the first step of pathogensis of thrombotic microangiopathy
loss of thromboresistance by the endothelial cell
157
what is the subsequent pathogenesis of thrombotic microangipathy
platelet activation - deposition of platelet and fibrin thrombi in lumen of affected vessels
158
where else may fibrin deposit in thrombotic microangiopathy
subintima and media of vessels
159
classic, but nonspecific appearance of vessel on biopsy of thrombotic microangiopathy
onion skinning (can also be HTN, etc)
160
thrombotic microangiopathy - what 3 things can cause endothelial damage
1) verotoxin producing E coli H7:O157 - may cause cytotoxic antiendothelial antibodies
2) chemo agents (cyclosporine, gemcitabine, bleomycin, cisplatin)
3) radiation - bone marrow transplant
161
TTP - ADAMTS13 - if this is acquired
1) what is pathogenesis
2) what is tx
1) autoantibodies to ADAMTS13
| 2) plasmapheresis
162
TMA vs DIC -
1) PT and PTT
2) diathesis (bleeding or thrombotic)
TMA
1) PT and PTT nml
2) thrombotic diathesis
DIC
1) PT and PTT elevated
2) bleeding diathesis
163
what renal disorder is seen w/ lupus
1) proteinuria
| 2) or - cellular casts - RBC, Hgb, granular, tubular, or mixed
164
Class I Lupus nephritis - pathogensis
minimal mesangial
165
Class II Lupus
mesangial proliferative - 15% - mild
166
Class III Lupus
Focal proliferative - 25% - moderate
167
Class IV Lupus
diffuse proliferative - 50% - severe
168
Class V Lupus
Membranous - 10%
169
Class VI Lupus
Advanced sclerosing
170
Lupus Class IV - histo features
lost of excess cells - inflammatory cells, mesangial cells, cpaillary endothelial cells - wireloop lesions, hyaline thrombus, crescent formation
171
Lupus V - rare, but what is a defining feature
nephrotic
172
Lupus - immunofluorescence - what all is present in deposits
Full house - IgG, IgM, IgA, C3 and C4
173
what tx of Lupus do you worry about adherence w/ (oral) and why
1) Mycophenolate mofetil
| 2) GI side effects
174
Mycophenolate Mofetil MOA
inhibition of Toll-like receptor
175
what are the 2 subtypes of scleroderma and which one are you more worried about for renal involvement
1) Diffuse cutaneous - more of a concern for renal involvement
2) limited cutaneous
176
scleroderma renal involvement - what is the manifestation
renal dysfunction, proteinuria, HTN
177
what is the tx of scleroderma renal crisis and what is unique about it
1) ACE I - highest tolerable level
2) scleroderma renal crisis is the one scenario where you will raise the ACE I as high as possible in the setting of renal dysfunction
178
what are the 4 risk factors for scleroderma renal crisis
1) early diffuse systemic sclerosis
2) rapidly progressive skin disease
3) anti-RNA polymerase antibdies
4) corticosteroid therapy
179
what renal arteries are affected in scleroderma and what is the manifestation
1) arcuate arteries
| 2) intimal and medial proliferation w/ luminal narrowing
180
scleroderma -
1) what arteries (besides arcuate) are affected
2) manifestation, what is the common slang
1) interlobar arteries
2) concentric sclerosing intimal thickening - "onion skinning" - of bigger arteries (150-200 microns d) than other diseases we have talked about
181
what is the definition of scleroderma renal crisis
new onset of accelerated arterial HTN and/or rapidly progressive oliguric renal failure
182
what subset of AKI is the worst cases
ATN
183
what % of ATN does ischemic ATN comprise
iscehmic ATN is around 75% of all the cases of ATN
184
3 gross pathologic features of ATN
1) size of kidney
2) cortex
3) medulla
1) enlarged - up to 30% over nml
2) pale cortex
3) congested medulla - especially at corticomedullary junction
185
for ischemic ATN, what is the most common cause for the ischemia?
shock, especially septic shock
186
what is a common gross kidney feature of ATN and what is the cause
1) cortical hemorrhages
| 2) septic emobli - somehow - something that unevenly affects the kidney
187
ATN - what are 2 features seen on histo associated with early ischemic changes
1) blebbing on the luminal side of the tubular epithelial cells - replace the brush border
2) vacuolization of cytoplasm - diffuse edema of tubular cells
188
ATN - what are 4 microscopic patho findings that are not the early 2
1) flattening of epithelium
2) necrosis
3) sloughing of epithelial cells into lumen
4) cells mixing into proteinaceous casts in lumen ("muddy brown")
189
ATN - what is another, very rare, feature seen on histo in addition to / opposed to necrosis
apoptosis of few tubular epithelial cells
190
ATN - histo - what can show up as dense, acellular, darkly eosinophilic casts in tubules
myoglobin -
191
ATN - what / how does myoglobin fit into the patho picture
crush injury or trauma - rhabdo - release of myoglobin
| the crush injury or trauma can also lead to shock which leads to ATN
192
ATN - see prominent cytoplasmic vacuolization and formation of oxalate crystals in tubular lumen - what is etiology
ethylene glycol poisoning
193
ATN - what is seen in recovery phase
mitosis
194
when does ATN become a medical emergency? what is the number?
hyperkalemia - K over 7 mmol/L
195
what is the tx of hyperkalemia
1) IV calcium gluconate - antagonizes membrane depolarization - guards against cardiac arrhythmias
2) IV insulin + glucose - drives potassium back into cells
196
Acute pyelonephritis - gross patho - dark red congestion and areas of light tan suppurative inflammation - what feature can be present in addition to necrosis
coalescing into abscesses
| know that acute pyelonephritis is abscessing (liquefactive necrosis)
197
pyonephrosis
pus replacing the kidney
198
perinephric abscess
abscess extending into adjacent tissue
199
pyelonephritis can extend out to capsule - causes necrosis - then what does it cause? what is characteristic feature of this?
1) cortical scar, depressed inwards
| 2) blunted calyx
200
what are 2 routes of cause of pyelonephritis and which is more common
1) ascending infection from the bladder (E coli) - most common
2) hematogenous spread (staph aureus)
201
what is the pattern of pyelonephritis associated w/ ascending
large area pyelonephritis - almost wedge shaped
202
pattern of pyelonephritis associated w/ hematogenous
foci of pyelonephritis - usually infection of individual glomeruli
203
chronic pyelonephritis - what inflammatory cells present and where do they land
1) lymphocytes and plasma cells
| 2) primarily interstitial
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chronic pyelonephritis - buzzword
| and cause
1) thyroidization
| 2) fibrosis and tubules distended w/ inspissated urine - make them look like thyroid follicles
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most common cause and % of acute interstitial nephritis (AIN)
drug reactions
| 75%
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AIN - in addition to usual inflammatory cell infiltrate (macs, lymphos, neutros) what else is characteristic of histo
edema
| eosinophils (least common, most specific)
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Analgesic nephropathy - what is the pathophys leading to papillary necrosis
chronic interstitial nephritis - corticomedullary junction - restricts blood flow to medulla - some liquefactive necrosis takes place - leads to ischemic necrosis of papillary tip - then sloughing off
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ADPKD - mutation in what protein is most common cause
polycystin - 1
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ADPKD - pathogensis
ciliopathy (due to defective polycystin) - defective mechnosensing of urine flow, dysregulation of cell adhesion
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ARPKD - (children) - mutation in what protein
fibrocystin
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what is sequalae of ARPKD
immediate untreatable respiratory failure at birth - pulmonary hypoplasia - b/c fetal kidneys do not produce enough amniotic fluid
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ARPKD - where do cysts form initially
down in collecting duct
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what is the most common genetic cause of ESRD in children?
nephronophthisis - medullary cystic disease complex
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what is nephronophthisis
small kidneys w/ numerous small cysts at corticomedullary junction and chronic tubulointerstital nephritis and fibrosis
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nephronophthisis - what are the mutations
9+ genes for cilia components
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medullary sponge kidney
"relatively common and usually innocuous condition" - nothing, compared to medullary cystic disease complex
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recall: what biochem feature causes sickle cell disease
substitution of a valine for glutamic acid as the 6h amino acid of the beta globin chain - Hgb tetramer is poorly soluble when deoxygenated
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Clinical manifestations of sickle cell
PAINFUL EPISODES due to hemolysis, symptomatic anemia, infetions, stroke, etc
(priapism)
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PBS of Sickle Cell
sickle cells, polychromasia (inc retics), Howell-Jolly bodies - hyposplenia, possible target cells
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impt lab findings for Sickle Cell
inc retic, hyperbilirubinemia, elevated serum LDH, low serum haptoglobin
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what will you see in sickle cell pt that indicates renal involvement
microalbuminuria - 60% of patients w/ hgb SS disease those over 45 years
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what percentage of pts w/ Hgb SS disease will develop end stage renal disease
4-12%
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What 3 features of (blank) part of the kidney cause a perfect storm for formation of sickles
(blank) = inner medulla
1) hypoxia - partial pressur of O2 10-35 mm Hg
2) acidosis
3) hyperosmolarity
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what happens to renal vasculature in sickle cell trait
the cortical vasculature is decreased; vasa recta attenuated
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what happens to renal vasculature in sickel cell disease
considerable decrease in cortical vasculature and vasa recta completely obliterated
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What are the two main clinical findings of sickle cell kidney problems?
1) hematuria
| 2) hyposthenuria (loss of concentrating ability of nephron)
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what is the clinical finding in early course of sickle cell renal problems
initially increased GFR
| manifest as lower creatinine than expected
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sickle cell renal involvement - what are the other features of shit going on in nephron
1) microalbuminuria - proteinuria
2) supranormal PT function - hyperphosphatemia and inc Cr secretion
3) impairment of distal hydrogen ion and K secretion
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early stages of sickle cell npehropathy - what will you see on histo
glomerular hypertorphy
hemosiderin deposits
focal areas of hemorrhage or necrosis
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later stages of sickle cell nephropathy - what will you see on histo
edema, fibrosis, tubular atrophy (bad news bears) and papillary infarcts -- papillary necrosis (impt)
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end stage of sickle cell nephroapthy
FSGS w/ glomerular enlargement (more hypertrophy than MPGN)
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AL amyloid - aka primary type - key feature of the immunoglobulins that are present
monoclonal
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AL (primary) - when circulate through the kidney what makes it to urine
free light chain - Bence Jones Proteins
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2 most common disease in US that lead to secondary (reactive - AA) type amyloidosis
1) Rheumatoid Arthritis
| 2) inflammatory bowel disease
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what has to present in the extracellular environment to allow for amyloidosis to occur
extracellular fibrillogenic environment w/ amyloid enhancing factor secreted by macrophages
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amyloidosis - what is key shape of the proteins and what is the importance of this
beta pleated sheets
| macrophages cannot clear the proteins in this conformation
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amyloidosis in the kidney - what are the 2 results of amyloid deposits that lead to poor kidney function
1) tubular atrophy
| 2) interstitial fibrosis
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what is a setback of the congo red stain
false negatives - looks peachy in color or more salmon (some might say it almost looks taupe)
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what is immunoperoxidase stain used for and what is a potential setback
1) diff type of amyloid
| 2) often false positives
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what is a key associaiton with Amyloid L (i.e. cause)
monoclonal gammopathy - b/c immunoglobulin light chains are usually monoclonal (although multiple myeloma can cause, less frequently)
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AL associated w/ diffuse symptoms overall -
1) BP
2) heart
3) GI
4) blood
1) not HTN
2) restrictive cardiomyopathy, sick sinus syndrome
3) GI dysmotility, malabsorption, hemorrhage or obstruction
4) bleeding diathesis
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what can happen when Bence Jones proteins preceipitate in th tubules and what does this look like
1) tubular epithelial cells coalesce into a syncytium around the BJ proteins
2) looks like a multinucleated giant cell
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what is the tx for AL
1) low dose melphalan and dexamethasone
| 2) high dose melphalan and autologous stem cell transplant in patients
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AA (reactive systemic) amyloidosis - what is third cause, in addition of RA and IBD
ankylosing spondlyitis
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AA produced in liver in response to what
IL-1 and IL-6
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AA kidney is the main target organ - what is the most common COD
pts end up on dialysis - most common COD is infection from dialysis related thing
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what is treatment for AA
eprodisate - limits deposition of amyloid A fibrils by interfering w/ their interaction w/ tissue glycosaminoglycans
slows renal decline but not risk of death
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what is cause of amyloid Beta2m
long-term hemodialysis
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where does amyloid Beta2m commonly deposit (this is impt)
synovium, joints, tendon sheaths
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amyloid TTR - what is function of transthyretin
transports thyroxine and retinol
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amyloid TTR - what are presenting complications
heart failure or arrhythmia
| commonly heart block - deposits in conducting system, blocking a bundle branch or something
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what disease is commonly associated w/ multiple myeloma
light chain deposition disease
253
light chain deposition disease - what doe we call it
a nonamyloid monoclonal immunoglobulin deposition disease (MIDD)
254
light chain dis (MIDD) - obviously congo red negative, what else are features (microscopic) of this
no fibrillar organization - precipitation of immunoglobulin chains without elongation seen in amyloid
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sicca syndrome - what are thinking
light chain deposition disease
| sicca - dry eyes, dry mouth
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general symptoms fo light chain deposition disease
proteinuria w/ renal failure, hepatomegaly, cardiomegaly, CHF, conduction disturbances, peripheral neuropathy, GI distrubances, pulmonary nodules, arthropathy, (similar to amyloidosis)
257
features of light chain disease on histo slide 3)
1) nodular glomerulosclerosis
2) expansion of mesangial matrix
3) deposits may be seen along the outer part of tubular basement membrane
strongly resembles diabetic nephropathy
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Light chain disease on IF - features
| and kappa or lambda more common
1) light up on capillary loops, mesangium and noted tubule involvemnt
2) kappa
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light chain disease - EM
endothelial cell side, looks like silk
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pt p/w nephrotic or RPGN, cardiac diastolic dysfunction, and monoclonal Ig in urine or serum
Light Chain disease - will see proteinuria, will need to identify (chemical analysis) the protein to determine monoclonal Ig
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MIDD - renal and patient survival better w/ what?
if no cast nephropathy, better survival
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pt has heavy proteinuria w/ minimal swelling and progressive azotemia - what are thinking
HIVAN
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HIVAN - buzz word of what you will see on light microscope histo
microcystic tubular dilatation
264
HIVAN - what else seen on histo (3)
1) collapsing form of FSGS,
2) intersitial inflammation and fibrosis
3) podocyte dedifferentiation and proliferation
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HIVAN - what is a key susceptibility allele and what pt population is this in
APOL1
| African Americans - show increased susceptiblity to HIVAN and other renal disease
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what tx can be used in HIVAN w/ only mild renal dysfunction
ACEI or ARB (should not be used in pts w/ advanced severe renal dysfunction)
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again, what are 2 features we see on histo for HIVAN
1) collapsing FSGS
| 2) microcystic tubular dilation w/ interstitial inflammation and fibrosis
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what is the patho of mixed cryoglobulinemia type II
B-cell lymphoproliferative disorder characterized by the deposition of immune ocmplexes
269
mixed cryoglobulinemia type II - what do the immune complexes contain (4)
rheumatoid factor (RF), IgG, HCV RNA, and complement
270
mixed cryoglobulinemia type II - where do immune complexes deposit and what does it cause
endothelial surfaces - elicits vascular inflammation (hematuria)
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what kind of renal disease picture does cryoglobulinemia lead to
MPGN (type 1?)
272
Meltzer's triad of purpura, arthralgia, and weakness - what disease
cryoglobulinemia
273
most common symptoms of cryo
cutaneous manifestations - erythematoous macules to purpuric papules
274
what type of Ig is RF
IgM - binds IgG
275
what type of glomerulopathy is amyloidosis
nonproliferative, noninflammatory
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what do we see on EM for amyloidosis
randomly oriented fibrils
