PATH: Kidney in Systemic Disease II Flashcards
How does sickle-cell disease cause nephropathy?
Vaso-occlusive crises involving glomerular and tubular capillaries. (Primarily from sickling within vasa recta which is in the hyperosmotic, acidic, and hyoxic medulla).
What is the most common manifestation of sickle-cell nephropathy?
proteinuria (microalbuminuria in 60% of patients over 40 with the homozygous hemoglobin SS)
What can sickle-cell nephropathy progress to?
ESRF in 4-15% of patients iwth homozygous hemoglobin SS
What is the early pathology of sickle-cell nephropathy?
glomerular hypertrophy
Hemosiderin deposits
Focal areas of hemorrhage/necrosis
What is the later pathology of sickle-cell nephropathy?
interstital inflammation edema tubular atrophy fibrosis RENAL PAPILLARY INFARCTS (but more commonly seen in diabetes)
What is the pathology of chronic sickle-cell nephropathy?
marked glomerular enlargement mesangial expansion segmental sclerosis abundant brown pigment in tubules Interstitial fibrosis/vascular sclerosis
What is the pathology of end-stage sickle-cell nephropathy?
focal segmental glomerulosclerosis
What all is located in an amyloid deosit?
1) disease specific fibrillogenic protein
2) Amyloid P (about 5%)
3) Proteoglycans (perlecan and heparin sulfate)
4) Apoprotein E
What are the Major types of amyloidosis that affect the kidney?
AL Amyloid
AA Amyloid
What type of amyloidosis occurs in patients on long-term dialysis?
A-Beta-2 microglobulin Amyloid
What type of amyloidosis is seen in Alzheimer disease?
A-beta amyloid (only in brain and blood vessels)
What proteins make up AL amyloid?
Ig Light Chains
What are urinated light chains called?
Bence-Jones proteins
What happens if Bence-Jones proteins get caught int he renal tubule?
renal tubular epithelial cells can form a syncytium around them that is similar to epithelial cells
What are the major s/s of AL amyloidosis?
WEakness, weight loss, nephrotic syndrome, enlarged kidney, peripheral/autonomic neuropathy (NOT hypertensive but can have GI and CV problems)
How do you treat AL amyloidosis?
Melphelan
Dexamethasone
ASCT in younger patients
What is the prognosis for AL amyloidosis?
10 months
What can be found in AA amyloid deposits?
Serum amyloid A, ApoE, basement membrane components (perlecan and laminin)
What helps to lay down AA amyloid?
amyloid enhancing factor
What makes amyloid A?
apoprotein for HDL made by hepatocytes (upregulated during inflammatory conditions with IL-1,2,6 and TNF)
How do you treat AA amyloidosis?
eprodisate
What is the prognosis for AA amyloidosis?
usually die from infection or dialysis related complication
What is light chain disease?
Non-amyloid monoclonal Ig Deposition Disease (MIDD). Precipitation of Ig chains without elongation seen in amyloidosis.
What is Light chain disease associated with ?
multiple myeloma
What are the s/s of light chain disease?
Proteinuria, renal failure with non-nephrotic range proteinuria and tubulointerstitial syndrome (rapidly declining renal function), hepatomegaly, cardiomegaly (with possible diastolic dysfunction)
What are the complication of light chain disease?
Can lead to peripheral neuropathy, GI problems, pulmonary nodules, sicca syndrome
What does light microscopy look like in light chain disese?
characteristic nodular glomeruloclerosis with expansion of mesangial matrix (do not confuse with diabetes)
What does IF look like in light chain disease?
kappa light chains in capillary loops, mesangium, tubules;
What does EM look like in light chain disease?
EM: endothelial-side deposition of silt-appearance material
What is the pathogenesis behind HIV-associated nephropathy?
Direct infection by HIV and expression of viral genes (Nef and Vpr) in renal epithelial cells that leads to collapsing FSGS
What does collapsing FSGS look like due to HIV?
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
What is deposited in the tubules in HIV-associated nephropathy?
proteinaceous material
What does Bowman’s capsule look like in HIV-associated nephropathy?
large with numerous protein droplets within
Who gets monoclonal cyoglobulinemia?
people with mutliple myeloma
What are the s/s of monoclonal cyoglobulinemia?
Hyperviscosity and Thrombosis related:
- Raynaud phenomenon
- Digital ischemia
- Purpura
- Gangrene
- Neurological problems
Who gets mixed cryoglobulinemia?
People with Hepatitis C
What is mixed cryoglobulinemia?
B-cell proliferative disorder resulting in the deposition of immune complexes with RhF, IgG, HCV RNA and complement in endothelium.
What is the pathology of cryoglobulinemia?
membranoproliferative pattern with hyaline (pseudo) thrombi projecting into capillary
