Robbins Chapter 20 - The Kidney - Part 2

Question 1

Destruction of glomeruli/reduction of GFR to 30-50%

Answer 1

ESRD progresses at a steady rate

Question 2

2 major characteristics of progressive renal damage

Answer 2

Principal injury- Focal segmental glomerulosclerosis

Accompaning injury - Tubulointerstitial fibrosis

Question 3

FSGS

Answer 3

Progressive fibrosis after injury
Increased proteinuria and impaired function
Initiated by adaptive change: compensatory hypertrophy of healthy areas of kidney

Reduction in renal mass -> HTN and hypertophy -> Epithelial damage -> proteinuria -> mesangial proliferation and macrophage infiltration -> accumulate ECM -> sclerosis
(vicious cycle)

Question 4

Interrupting glomerulosclerosis process

Answer 4

Renin-angiotensin inhibitors

reduce HTN and inhibit compensatory mechanisms

Question 5

Tubulointerstitial fibrosis

Answer 5

Tubular damage and interstitial inflammation

Better correlation in decline of renal function

Ischemia downstream, surrounding inflammation, or loss of peritubular capillary network

Proteinuria can directly injure and activate tubular cells

Question 6

Nephritic syndrome

Answer 6

Inflammation of glomeruli

**Hematuria, red cell casts in urine, azotemia, oliguria, mild to moderate HTN
Proteinuria and edema are common but not as severe

Question 7

Acute proliferative glomerulonephritis/ Postinfectious Glomerulonephritis

Answer 7

Diffuse proliferation of glomerular cells
Influx of leukocytes
Typically cause by immune complexes

Question 8

Poststreptococcal Glomerulonephritis

Answer 8

1-4 weeks post group A strep infection with certain M proteins (12, 4 and 1)
Usually children age 6-10
Immune complexes formed in situ

Elevated antibody titers, decreased serum complement, granular immune deposits

Question 9

SpeB

Answer 9

Principle antigenic determinant for poststrep GN

Question 10

Poststrep GN Morphology

Answer 10

Enlarged, hypercellular glomeruli
IgG, C3 and IgM deposits in mesangium and GBM - focal and sparse
Subepithelial humps
Subendothelial deposits early on

Question 11

Poststrep GN Clinical course

Answer 11

Young child with malaise, fever, nausea, oliguria, hematuria (coke colored urine) 1-2 weeks after sore throat

Mild proteinuria, periorbital edema, mild HTN
Adult more atypical with sudden HTN, edema and BUN

95% children recover with minimal therapy
60% adults recover quickly
Small numbers progress to rapid progressive GN

Question 12

Nonstrep Acute GN

Answer 12

Similar course with staph, pneumonia, meningococcemia, hep B, hep C, HIV, varicella, mono, malaria, toxo

Staph differs by sometimes creating IgA deposits

Question 13

Rapid progressive GN

Answer 13

No specific etiology
Rapid loss of function
Severe oliguria and nephritic signs
Death in weeks to months
Crescents in most glomeruli
**Immunologically mediated - 3 types

Question 14

Type 1 - anti GBM

Answer 14

Linear immune deposits in GBM

Antibodies to portion of collagen IV alpha3 chain

Question 15

Goodpasture syndrome

Answer 15

Antibodies cross react
Pulmonary hemorrhage (recurrent hemoptysis) with renal failure

Question 16

HLA-DRB1

Answer 16

Associated with type 1 (autoimmunity)

Question 17

Type 2 - immune complex deposition

Answer 17

Complication of any immune complex nephritides

Postinfectious, SLE, IgA nephropathy, and Henoch-Schonlein purpura

Question 18

Type 3 - Pauci-immune

Answer 18

Lack of detectable anti-GBM or immune complexes
Circulating antineutrophil cytoplasmia antibodies
May be associated with Wegener granulomatosis but usually idiopathic
**Manifestation of small vessel vasculitis or polyangiitis limited to peritubular capillaries

Question 19

Wegener granulomatosis

Answer 19

Granulomatosis with polyangiitis

Inflammation of blood vessels restricting blood flow to certain organs

Question 20

RPGN morphology

Answer 20

Distinctive crescents with prominent fibrin strands

May show ruptures in GBM - allows leukocytes and coagulation material through

Question 21

RPGN clinical course

Answer 21

Hematuria with blood cell casts, moderate proteinuria, variable HTN and edema
Serum analysis can be helpful (antiGBM, antinuclear, ANCAs)
Culminates in oliguria
Serum exchange may help some early on as well as steroid treatment
Many patients require chronic dialysis

Question 22

Nephrotic syndrome

Answer 22

Derangement in glomerular capillary walls resulting in increased permeability to plasma proteins

Massive proteinuria (greater than 3.5 gm)
Hypoalbuminemia (less than 3 gm)
General edema
Hyperlipidemia and lipiduria

Vulnerable to infection - loss of immunoglobulins
Thrombotic/thromboembolic complications - loss of anticoagulants -> renal vein thrombosis

Question 23

Generalized edema

Answer 23

Decreased colloid osmotic pressure or increased hydrostatic pressure (increased sodium and water retention)

Question 24

Highly selective proteinuria

Answer 24

Mostly low weight proteins (albumin)

Question 25

Poorly selective proteinuria

Answer 25

Variety of protein loss, low and high weight

Question 26

Most frequent cause of nephrotic syndrome in under 17 in NA

Answer 26

Lesion primary to the kidney

Question 27

Most frequent cause of nephrotic syndrome in adults in NA

Answer 27

Systemic disease

Question 28

Most frequent systemic cause of nephrotic syndrome

Answer 28

Diabetes, amyloidosis, SLE

Question 29

Most frequent primary lesions causing nephrotic syndrome

Answer 29

Minimal-change disease (children), membranous glomerulopathy (adults) and focal segmental glomerulosclerosis

Question 30

Less common cause of nephrotic syndrome

Answer 30

Proliferative glomerulonephritides: MPGN and IgA nephropathy

Question 31

Membranous Nephropathy

Answer 31

Diffuse thickening of glomerular capillary wall due to deposits of Ig on subepithelial side 75% primary 25% secondary/systemic problem

Question 32

Systemic causes of membranous nephropathy

Answer 32

Drugs (penicilamine, captopril, gold, NSAIDS) Malignant tumors (lung, colon, melanoma) SLE (10-15%) Infections (hep B, hep C, syphilis, schistosomiasis, malaria) Other autoimmune

Question 33

Membranous Nephropathy Pathogenesis

Answer 33

Chronic immune complex mediated Secondary - known antigens Primary - idopathic, linked to HLA-DQA1, usually antibodies to renal autoantigen (phospholipase A receptor) C5b-C9 MAC makes capillary leaky

Question 34

Membranous Nephropathy Morphology

Answer 34

Diffuse thickening of glomerular capillary wall on subepithelial side Segmental sclerosis may eventually occur

Question 35

Membranous Nephropathy clinical course

Answer 35

Usually insidious onset of nephrotic syndrome Proteinuria nonselective Does not respond well to corticosteroids Progressive sclerosis leads to increased creatinine and BUN and HTN 10% renal failure, 40% chronic disease Recurs in 40% who receive transplant for ESRD

Question 36

Minimal change disease

Answer 36

Relatively benign Diffuse effacement of foot processes, glomerulus appears normal, no deposits, lipoprotein reabsorption Peak incidence between age 2 and 6 Some form of immune dysfunction - angiopoietin-like-4

Question 37

Minimal change disease clinical course

Answer 37

Massive proteinuria, renal function remains ok without hematuria and HTN Drastically respond to corticosteroids although it may recur and individual may become steroid dependent

Question 38

Minimal change disease associated with

Answer 38

``` Hodgkin lymphoma in adults as well as other lymphomas and leukemias NSAID therapy (acute interstitial nephritis) ```

Question 39

Most common cause of nephrotic syndrome in adults in US

Answer 39

Focal Segmental Glomerulosclerosis

Question 40

Focal Segmental Glomerulosclerosis

Answer 40

Sclerosis of some glomeruli and only portion (segment) of capillary tuft is involved Higher incidence of hematuria, reduced GFR and HTN Proteinuria more nonselective Poor response to corticosteroids 50% develop ESRD

Question 41

Types of FSGS

Answer 41

``` Primary - idiopathic In association - HIV, heroin use, sickle-cell, obesity Secondary event - scarring Adaptive response to loss of tissue May be inherited ```

Question 42

Idiopathic FSGS

Answer 42

10% nephrotic syndrome in children | 35% nephrotic syndrome in adults

Question 43

FSGS Pathogenesis

Answer 43

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