PATH: Kidney in Systemic Disease II

Question 1

How does sickle-cell disease cause nephropathy?

Answer 1

Vaso-occlusive crises involving glomerular and tubular capillaries. (Primarily from sickling within vasa recta which is in the hyperosmotic, acidic, and hyoxic medulla).

Question 2

What is the most common manifestation of sickle-cell nephropathy?

Answer 2

proteinuria (microalbuminuria in 60% of patients over 40 with the homozygous hemoglobin SS)

Question 3

What can sickle-cell nephropathy progress to?

Answer 3

ESRF in 4-15% of patients iwth homozygous hemoglobin SS

Question 4

What is the early pathology of sickle-cell nephropathy?

Answer 4

glomerular hypertrophy
Hemosiderin deposits
Focal areas of hemorrhage/necrosis

Question 5

What is the later pathology of sickle-cell nephropathy?

Answer 5

interstital inflammation
edema
tubular atrophy
fibrosis
RENAL PAPILLARY INFARCTS (but more commonly seen in diabetes)

Question 6

What is the pathology of chronic sickle-cell nephropathy?

Answer 6

marked glomerular enlargement
mesangial expansion
segmental sclerosis
abundant brown pigment in tubules
Interstitial fibrosis/vascular sclerosis

Question 7

What is the pathology of end-stage sickle-cell nephropathy?

Answer 7

focal segmental glomerulosclerosis

Question 8

What all is located in an amyloid deosit?

Answer 8

1) disease specific fibrillogenic protein
2) Amyloid P (about 5%)
3) Proteoglycans (perlecan and heparin sulfate)
4) Apoprotein E

Question 9

What are the Major types of amyloidosis that affect the kidney?

Answer 9

AL Amyloid

AA Amyloid

Question 10

What type of amyloidosis occurs in patients on long-term dialysis?

Answer 10

A-Beta-2 microglobulin Amyloid

Question 11

What type of amyloidosis is seen in Alzheimer disease?

Answer 11

A-beta amyloid (only in brain and blood vessels)

Question 12

What proteins make up AL amyloid?

Answer 12

Ig Light Chains

Question 13

What are urinated light chains called?

Answer 13

Bence-Jones proteins

Question 14

What happens if Bence-Jones proteins get caught int he renal tubule?

Answer 14

renal tubular epithelial cells can form a syncytium around them that is similar to epithelial cells

Question 15

What are the major s/s of AL amyloidosis?

Answer 15

WEakness, weight loss, nephrotic syndrome, enlarged kidney, peripheral/autonomic neuropathy (NOT hypertensive but can have GI and CV problems)

Question 16

How do you treat AL amyloidosis?

Answer 16

Melphelan
Dexamethasone
ASCT in younger patients

Question 17

What is the prognosis for AL amyloidosis?

Answer 17

10 months

Question 18

What can be found in AA amyloid deposits?

Answer 18

Serum amyloid A, ApoE, basement membrane components (perlecan and laminin)

Question 19

What helps to lay down AA amyloid?

Answer 19

amyloid enhancing factor

Question 20

What makes amyloid A?

Answer 20

apoprotein for HDL made by hepatocytes (upregulated during inflammatory conditions with IL-1,2,6 and TNF)

Question 21

How do you treat AA amyloidosis?

Answer 21

eprodisate

Question 22

What is the prognosis for AA amyloidosis?

Answer 22

usually die from infection or dialysis related complication

Question 23

What is light chain disease?

Answer 23

Non-amyloid monoclonal Ig Deposition Disease (MIDD). Precipitation of Ig chains without elongation seen in amyloidosis.

Question 24

What is Light chain disease associated with ?

Answer 24

multiple myeloma

Question 25

What are the s/s of light chain disease?

Answer 25

Proteinuria, renal failure with non-nephrotic range proteinuria and tubulointerstitial syndrome (rapidly declining renal function), hepatomegaly, cardiomegaly (with possible diastolic dysfunction)

Question 26

What are the complication of light chain disease?

Answer 26

Can lead to peripheral neuropathy, GI problems, pulmonary nodules, sicca syndrome

Question 27

What does light microscopy look like in light chain disese?

Answer 27

characteristic nodular glomeruloclerosis with expansion of mesangial matrix (do not confuse with diabetes)

Question 28

What does IF look like in light chain disease?

Answer 28

kappa light chains in capillary loops, mesangium, tubules;

Question 29

What does EM look like in light chain disease?

Answer 29

EM: endothelial-side deposition of silt-appearance material

Question 30

What is the pathogenesis behind HIV-associated nephropathy?

Answer 30

Direct infection by HIV and expression of viral genes (Nef and Vpr) in renal epithelial cells that leads to collapsing FSGS

Question 31

What does collapsing FSGS look like due to HIV?

Answer 31

prominent microcystic tubular dilation and interstitial inflammation and fibrosis with podocyte de-differentiation and proliferation due to retraction of each of the individual lobules of the glomerulus

Question 32

What is deposited in the tubules in HIV-associated nephropathy?

Answer 32

proteinaceous material

Question 33

What does Bowman's capsule look like in HIV-associated nephropathy?

Answer 33

large with numerous protein droplets within

Question 34

Who gets monoclonal cyoglobulinemia?

Answer 34

people with mutliple myeloma

Question 35

What are the s/s of monoclonal cyoglobulinemia?

Answer 35

Hyperviscosity and Thrombosis related: - Raynaud phenomenon - Digital ischemia - Purpura - Gangrene - Neurological problems

Question 36

Who gets mixed cryoglobulinemia?

Answer 36

People with Hepatitis C

Question 37

What is mixed cryoglobulinemia?

Answer 37

B-cell proliferative disorder resulting in the deposition of immune complexes with RhF, IgG, HCV RNA and complement in endothelium.

Question 38

What is the pathology of cryoglobulinemia?

Answer 38

membranoproliferative pattern with hyaline (pseudo) thrombi projecting into capillary