Renal Path 2 Flashcards
80% of pts with a family hx of hematuria or recurrent hematuria during childhood have a hereditary form of nephritis. What are the 2 main conditions?
Alport syndrome
Thin basement membrane disease (benign familial hematuria)
Inheritance and Manifestations of Alport syndrome
X-linked inheritance in 85% of cases
Hematuria with progression to chronic renal failure; accompanied by nerve deafness, and various eye disorders including lens dislocation, posterior cataracts, and corneal dystrophy
Electron microscopy findings of alport syndrome
Irregular thickening of basement membrane
Delamination of lamina dense and foci of rarefaction … “moth-eaten” and “frayed” appearance
Clinical characteristics of thin basement membrane disease; what causes the thin membrane?
Characterized by microscopic, asymptomatic hematuria
Renal function is unremarkable and progression to end stage disease is uncommon
Anomaly of thin basement membranes is d/t mutations in genes encoding a3 or a4 chains of type IV collagen
Most pts are heterozygous for the defective gene (carriers); Homozygotes resemble AR Alport syndrome
Does SLE more commonly present as nephritic syndrome or nephrotic syndrome?
60-70% present as Nephritic syndrome
Secondary renal diseases that present as nephrotic syndrome (proteinuria)
Diabetic nephropathy
SLE (15% of pts)
Hepatitis C —Cryoglobulinemia (MPGN type I)
HIV nephropathy (FSGS)
Secondary renal diseases that present as nephritic syndrome (hematuria)
SLE (60-70% of pts)
Bacterial endocarditis (acute proliferative glomerulonephritis)
Goodpasture (RPGN)
Henoch-Schonlein Purpura (IgA nephropathy)
Compared to non-Hispanic whites, what ethnic groups are 1.5-2x more likely to develop diabetes in their lifetimes?
Native Americans
African Americans
Hispanics
In the US, _____ is the leading cause of ESRD, adult-onset blindness, and non-traumatic lower extremity amputation d/t atherosclerosis of arteries?
Diabetes mellitus
Differentiate type 1 from type 2 DM
Type 1 = autoimmune; characterized by pancreatic beta cell destruction + absolute deficiency of insulin. Abs may include anti-insulin, anti-GAD, anti-ICA512
Type 2 = combo of peripheral resistance to insulin action + inadequate secretory response by pancreatic beta cells
NOTE that the long term complications affecting multiple organs are the same for both types
What 2 major processes play key pathophysiologic roles as diabetic glomerular lesions develop?
A metabolic defect linked to hyperglycemia and advanced glycosylation end products produces thickened GBM and increased mesangial matrix
Hemodynamic effects associated with glomerular hypertrophy also contribute to the development of glomerulosclerosis
Describe histologic features of diabetic nephropathy
Markedly thickened tubular and glomerular basement membranes
Diffuse mesangial sclerosis (increased mesangial matrix — leads to narrowing of capillary lumen)
Nodular glomerulosclerosis — nodular appearance is prototypic/characteristic of diabetic glomerulosclerosis!!
Histologic features of advanced renal hyaline arteriolosclerosis
Markedly thickened, tortuous afferent arteriole
Amorphous (thickened) vascular wall
Gross appearance of end-stage diabetic kidneys
Overall shrunked kidneys with diffusely granular pitted surface
Marked thinning of renal cortex
May see irregular cortical depressions secondary to pyelonephritis
3 renal system lesions prototypical of diabetic nephropathy
- Glomerular lesions
- Vascular lesions (principally arteriolosclerosis)
- Pyelonephritis (including necrotizing papillitis)
T/F: DM starts as a macrovascular disease and progresses to affect smaller and smaller vessels at which point it is classified as a microvascular disease
False!
Starts out as a microvascular disease leading to issues like arteriolar nephrosclerosis
Over time and with poor control it becomes a macrovascular disease, affecting larger vessels and leading to complications such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents (most common causes of mortality in long-standing DM)
What disease is characterized by renal glomerular capillary basement membrane with subendothelial dense deposits (“wire loops”) and deposits present in mesangium?
SLE
Clinical features + Histologic changes in diffuse proliferative lupus nephritis
Clinically: pts are usually symptomatic with hematuria as well as proteinuria. HTN and mild to severe renal insufficiency are also common
Histology:
Hypercellularity
Glomerulus greatly enlarged, appearing “stuffed” into Bowman’s capsule with resultant decrease in urinary space
Appears almost identical to diffuse proliferative glomerulonephritis seen in post-strep cases — so must correlate biopsy with patient history!
Diffuse proliferative lupus nephritis would show mesangial and subendothelial capillary wall ____ localization
IgG
What are the 6 patterns of glomerular disease seen in SLE pts? Which one is most vs. least common?
Class I: Minimal mesangial lupus nephritis (LEAST common)
Class II: Mesangial proliferative lupus nephritis
Class III: Focal lupus nephritis
Class IV: Diffuse lupus nephritis (MOST common)
Class V: Membranous lupus nephritis
Class VI: Advanced sclerosing lupus nephritis
Most common cause of acute renal failure
Acute tubular injury/necrosis
2 most common etiologies of acute tubular injury
Ischemia — either d/t decreased ECV (hypotension, shock) or diffuse involvement of intrarenal blood vessels in conditions such as malignant HTN; microangiopathies and systemic conditions associated with thrombosis (HUS, TTP, DIC)
Direct toxic injury (drugs, toxins like ethylene glycol/antifreeze)
[uncommon causes include acute tubulointerstitial nephritis or urinary obstruction]
Primary clinical manifestation of reduced GFR d/t acute tubular injury
Oliguria
Patterns of tubular damage in acute tubular injury d/t ischemia vs. toxicity
Ischemic damage:
Patchy necrosis of PCT, PST, and TAL
Toxic damage:
Continuous necrosis of PCT and PST, patchy necrosis of TAL
