Kidney Systemic Disease II

Question 1

sickle cell nephropathy - where in the kidney does sickling happen?

Answer 1

inner medulla

Question 2

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?

Answer 2

1) relative hypoxia
2) acidosis
3) hyperosmolarity

Question 3

what pathologic, structural functional change does sickle cell nephropathy cause over time in the kdiney?

Answer 3

considerable decrease in the cortical vasculature and the vasa recta are virtually absent

Question 4

pt comes in with microalbuminuria, hyposthenuria (decrease of concentrating ability) - your differential could include nephrogenic DI and what else

Answer 4

sickle cell -

Question 5

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?

Answer 5

1) increased GFR in early childhood, young adulthood - hyperfiltration
2) you will see a lower creatinine than expected (in plasma)

Question 6

sickle cell - what is an impt histo feature you see on biopsy

Answer 6

papillary infarcts / necrosis

Question 7

sickle cell - what other pathological processes will be present seen on biopsy of the later stages

Answer 7

interstitial inflammation, edema, tubular atrophy and fibrosis

Question 8

what does sickle cell nephropathy common progress to as end stage

Answer 8

ESRD – FSGS w/ glomerular enlargement

Question 9

sickle cell - if he has a picture of a LM kidney biopsy slide, what general things would you see

Answer 9

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

Question 10

glomerulomegaly and mesangial expansion; tubular epithelial hemosiderin acumulation; interstitial fibrosis and vascular sclerosis

Answer 10

sickle cell nephropathy

Question 11

amyloidosis - misfolded proteins - what do they fold into

Answer 11

beta pleated sheets

Question 12

amyloidosis - where do deposits get put first

Answer 12

blood vessel walls

Question 13

amyloidosis - what causes organ failure

Answer 13

deposits get into the interstitium, stuff squeezes the cells to death

Question 14

AL (primary) amyloid - what is the abnormal protein

Answer 14

immunoglobulin light chain (usually lambda)

Question 15

AL amyloid - what is a feature of the disease underlying

Answer 15

monoclonal *** gammopathy

I think this will be on test

Question 16

what do we call light chains that get into the urine

Answer 16

Bence Jones proteins

Question 17

pt comes in with either Rheumatoid Arthritis or Inflammatory Bowel Disease - what are you thinking (amyloid)

Answer 17

AA - secondary reactive amyloid

RA and IBD - 2 most common systemic diseases giving rise to this reactive type amyloid

Question 18

AA - secondary amyloidosis - what is the cause in general

Answer 18

a systemic chronic inflammatory disease

Question 19

what molecule needs to be present in order to have amyloidosis formation (i.e. fibril formation)

Answer 19

AEF - amyloid enhancing factor

without this, will not have amyloidosis - just having circulating amyloid is not enough

Question 20

amyloid kidney - what kind of glomerulopathy is seen? what will you see on urinalysis

Answer 20

1) nonproliferative, noninflammatory

2) proteinuria, NOT hematuria

Question 21

w/ renal amyloidosis, what is the size of the kidneys

Answer 21

enlarged

Question 22

what are the 2 pathological processes in the kidneys that are end result of amyloidosis (bad news bears)

Answer 22

tubular atrophy and interstitial fibrosis

Question 23

what stain do you use for amyloidosis?

Answer 23

congo red

Question 24

what is a setback with congo red ?

Answer 24

can get false negatives
does not always appear very red
(can look tan, peachy, salmon, some may even say taupe)

Question 25

congo red can never tell you what type of amyloid is present. what test can?

Answer 25

immunoperoxidase stain

Question 26

what is a setback of immunoperoxidase stain

Answer 26

false positives

Question 27

do you see HTN w/ AL amyloidosis

Answer 27

no

Question 28

note that amyloidosis AL is associated with GI symptoms

Answer 28

GI dysmotility, malabsorption, hemorrhage or obstruction

Question 29

what is the treatment for AL? what is the prognosis?

Answer 29

1) melphalan and dexamethasone (if pt younger than 50, can do autologous stem cell transplant) 2) shitty - median survival 10 months

Question 30

what is a third cause of AA

Answer 30

ankylosing spondlyitis

Question 31

what abnormal protein si involved with AA amyloid? | what is it produced in response to?

Answer 31

1) serum amyloid A protein | 2) acute phase reactant produced by liver in response to IL-1 and IL-6

Question 32

what is a new treatment option for AA

Answer 32

eprodisate - limits deposition of amyloid A fibrils by interfering w/ their interaction w/ tissue glycosaminoglycans

Question 33

what is most common cause of death in AA

Answer 33

death usually from infection or dialysis related complication - b/c most AA pts end up on dialysis in end

Question 34

what type of amyloidosis occurs with long term hemodialysis

Answer 34

Amyloid beta2m | this is beta 2 microglobulin

Question 35

where does amyloid beta2m prefer to deposit

Answer 35

synovium, joints, and tendon sheaths | this is unique and he kind of emphasized it

Question 36

amyloidosis type that presents with heart failure and arrhythmia

Answer 36

amyloid TTR - transthyretin

Question 37

what is the function of transthyretin

Answer 37

transporter protein for thyroxine and retinol (notice how the name "transthyretin" actually describes its function)

Question 38

what is another name for light chain deposition disease

Answer 38

nonamyloid monoclonal immunoglobulin deposition disease (MIDD)

Question 39

light chain deposition disease (MIDD) - what underlying disease

Answer 39

multiple myeloma

Question 40

sicca syndrome 1) what is it? 2) if you see this in a question stem, what disease are you thinking?

Answer 40

1) dry eyes, dry mouth | 2) light chain deposition disease (MIDD)

Question 41

for light chain disease, what other disease does the histo resemble?

Answer 41

diabetic nephropathy nodular glomerulosclerosis expansion of mesangial matrix

Question 42

what is unique about the protein assocaited with light chain disease

Answer 42

kappa is more common than lambda (diff from AL)

Question 43

light chain disease on EM - where does it deposit and what is the buzz word for what it looks like

Answer 43

1) endothelial cell side (subendothelial) | 2) silt

Question 44

if you see the combination of "heavy proteinuria" and "minimal swelling" what are you thinking

Answer 44

HIV associated nephropathy (HIVAN)

Question 45

HIVAN - what is the classical glomerulopathy

Answer 45

collapsing form of focal segmental glomerulosclerosis

Question 46

what is the buzz word finding on histo for HIVAN

Answer 46

microcystic tubular dilatation

Question 47

what is a key susceptibility allele associated with HIVAN

Answer 47

APOL1

Question 48

palpable purpura, arthralgia, elevated serum RF in a Hep C patient - what is the diagnosis

Answer 48

mixed cryoglobulinemia type II

Question 49

what is the pathogenesis of cryoglobulinemia

Answer 49

deposition of immune complexes on endothelial surface, activation of complement and eliciting vascular inflammation

Question 50

what will you see on urinalysis of cryo? (think inflammation)

Answer 50

hematuria

Question 51

cryo - what kind of disease picture of the glomerulus seen on renal biopsy

Answer 51

MPGN

Question 52

purpura, arthralgia, and weakness - what is this and what disease is it associated with

Answer 52

Meltzer's triad - associated with cryo

Question 53

what kind of immunoglobulin is RF

Answer 53

IgM -- binds IgG

Question 54

what is seen on EM with amyloidosis

Answer 54

randomly oriented fibrils

Question 55

what is a key diagnostic feature of light chain disease? (recall, it is not true amyloidosis)

Answer 55

congo red negative

Question 56

cryo - what is contained in the immune complexes

Answer 56

RF, IgG, HCV RNA, and complement