Renal - Glomerular Pathology

Front 1

Nephrotic Syndrome

--general clinical findings(3)

Back 1

1. Marked proteinuria (>3.5g)
2. Peripheral edema
3. Lipiduria, hyperlipidemia

Hint 1

pg 16

Front 2

Acute Nephritic Syndrome

--general clinical findings(3)

Back 2

1. Hematuria (gross or micro)
2. Proteinuria (mild to moderate)
3. HTN

Hint 2

pg 16

Front 3

Acute Renal Failure

--general clinical findings(3)

Back 3

1. Anuria/oliguria
2. Azotemia (abnormal levels of nitrogen-containing compounds -- urea, creatinine)
3. Acute onset -- days to weeks

Hint 3

pg 16

Front 4

Nephrotic Syndrome

--definition

Back 4

--defined by a urinary protein loss > 3.5g/24hr, resulting in hypoalbuminemia, peripheral edema, hyperlipidemia as well as an increased propensity for infection and hypercoaguability

Hint 4

pg 16

Front 5

Nephrotic Syndrome

-differential diagnosis in children

Back 5

Primary Renal Disease (95%)
1. Minimal Change Disease (65%)
2. Focal Segmental Sclerosis (10%)
3. Membranoproliferative GN (10%)
4. Membranous GN (5%)

Secondary Renal Disease (5%)
1. Uncommon in children -- SLE

Hint 5

pg 16

Front 6

Nephrotic Syndrome

-differential diagnosis in adults

Back 6

Primary Renal Disease (60%)
1. Focal Segmental Sclerosis (60%)
2. Membranous GN (33%)
3. Minimal Change Disease (15%)
4. IgA Nephropathy (9%)
5. Membranoproliferative GN (2%)
6. Other (6%)

Secondary Renal Disease (40%)
1. DM
2. SLE
3. Amyloidosis

Hint 6

pg 16

Front 7

Minimal Change Disease

-epidemiology
-pathogenesis

Back 7

--#1 cause of nephrotic syndrome in children

--Primary podocyte injury of unknown cause; perhaps due to a circulating, non-antibody, immune related substance --> reduction of poly-anionic components of GBM with loss of fixed (-) charges --> increased loss of small (-) charged proteins in urine (albumin)

Hint 7

pg 16

Front 8

Minimal Change Disease

-LM
-IF
-EM

Back 8

LM: NORMAL
IM: Negative
EM: Diffuse podocyte foot process effacement (lose foot processes) -- no immune complexes are noted

Hint 8

pg 16

Front 9

Focal Segmental Glomerulosclerosis - primary

-epidemiology
-pathogenesis

Back 9

--most common cause of nephrotic syndrome in AA, #2 in children

--strong evidence FSGS is caused by circulating factor that is not an antibody, but someway related to the immune system

Hint 9

pg 16

Front 10

Focal Segmental Glomerulosclerosis - primary

-LM
-IF
-EM

Back 10

LM: scattered glomeruli, less than 50% in early biopsies, show collapse of loops adjacent to the vascular pole with obliteration of capillary loops of that portion of the glomerulus w/scarring or sclerosis.
IF: negative
EM: diffuse podocyte injury, as in minimal change disease, with effacement of foot processes, no immune deposition

Hint 10

pg 17

Front 11

Focal Segmental Glomerulosclerosis - secondary

-pathogenesis

Back 11

When the # of glomeruli are decreased due to developmental abnormalities or diseases, the remaining glomeruli become hypertrophic and there is an increase in glomerular blood pressureand filtration to compensate for the decreased number of nephrons --> damage to the glomerulus

Hint 11

pg 17

Front 12

Focal Segmental Glomerulosclerosis - collapsing glomerulopathy

-epidemiology

Back 12

--Classical association with HIV infection, IV drug use and AA

--virulent, rapidly progressive disorder marked by massive proteinuria and end stage renal disease w/in 13 months

Hint 12

pg 18

Front 13

Focal Segmental Glomerulosclerosis - collapsing glomerulopathy

-LM
-IF
-EM

Back 13

LM: segmental, often global, collpase of glomerular tufts with prominent hypertrophy and injury of overlying podocytes
IF: negative
EM: podocye foot process effacement

Hint 13

pg 18

Front 14

Membranous Glomerulopathy

-epidemiology
-secondary causes (4)

Back 14

--most common cause of nephrotic syndrome in adult caucasians
--most cases (85%) in adults are idiopathic, but the remaining are:
1. Chronic infection -malaria, syphilis, hep B
2. Autoimmune disease - SLE, RA
3. Cancer - colon most common
4. Medication - Au, penicillamine, captopril

Hint 14

pg 18/19

Front 15

Membranous Glomerulopathy

-pathogenesis

Back 15

--immune complex mediated disease
--auto-antibodies react with podocyte cell surface antigens and activate compliment (c5-9) injuring the podocyte and adjacent GBM --> complexes are capped and shed into the subepithelial space and can be recognized on IF and EM --> GBM reacts to deposits by "growing up" b/t the deposits and eventually incorporating them into the GBM --> thickened GBM

Hint 15

pg 19

Front 16

Membranous Glomerulopathy

-LM
-IF
-EM

Back 16

LM: Diffuse, uniform thickening of GBM without an increase in cellularity
IF: Coarse, regular, granular staining of the GBM; usually with IgM and C3
EM: Inumerable, subepithelial, immune complex type, dense deposits with overlying foot process injury and effacement

Hint 16

pg 19

Front 17

Membranoproliferative GM -- type 1

-classification
-when to suspect it

Back 17

While often listed as causing nephrotic syndrome, this disorder may be associated with asymptomatic hematuria/proteinuria, acute nephritic syndrome, or a mixed nephritic/nephrotic presentation
--suspect when patients with nephrotic range proteinuria (>3.5g) who also have large numbers of red cells in urinalysis or evidence of renal failure with an increase in creatinine

Hint 17

pg 19

Front 18

Membranoproliferative GM -- type 1

-epidemiology
-pathogenesis

Back 18

--affects primarily children and young adults

--immune complex mediated disease, complexes are deposited in the mesangium and subendothelial space --> activates compliment --> attracts inflammatory cells --> injures endothelial cells and GBM

Hint 18

pg19/20

Front 19

Membranoproliferative GM -- type 1

-secondary causes (3)

Back 19

1. Chronic infection -- Hep B, Hep C, subacute bacterial endocarditis, deep visceral abscess
2. Immune disorders -- SLE, cryoglobulinemia
3. Malignancies -- "paraneoplastic syndrome

Hint 19

pg 19

Front 20

Membranoproliferative GM -- type 1

-LM
-IF
-EM

Back 20

LM: glomeruli are hypercellular, w/mesangial hypercellularity and endocapillary proliferation. GBM is mildly to markedly thickened.
IF: peripheral capillary loop and mesangial staining for IgG and C3
EM: subendothelial electron dense immune type deposits are seen in the subendothelial space. Mesangial cell interpositioning occurs with GBM reduplication. Deposits are also seen in the mesangium

Hint 20

pg 19

Front 21

Acute Nephritic Syndrome

--characterization of syndrome
--most common cause

Back 21

--Characterized by hematuria (gross or microscopic); proteinuria (not usually in nephrotic range); HTN; and mild renal insufficiency -- mildly elevated serum Cr.

--usually caused by acute post-infectious GN; most commonly post-streptococcal GN

Hint 21

pg 20

Front 22

Acute nephritic syndrome -- Post-strep GN

-clinical factors

Back 22

1. abrupt onset, 1-3 weeks after throat infection or 3-6 weeks after skin infection
2. edema, HTN, hematuria, azotemia, mild proteinuria and oliguria
3. anti-Streptolysin O titers or titers of anti-DNAase B are helpful in diagnosing past strep pyogenes infection
4. early in the disease, complement levels (C3 and C4) are often prominently decreased

Hint 22

pg 20

Front 23

Acute nephritic syndrome -- Post-strep GN

-pathogenesis

Back 23

Immune complex mediated disease

--circulating immune complexes associated with the Streptococcal infection are deposited in the glomerulus, or circulating strep-antigens become planted in the glomerulus and antibodies bind to them

Hint 23

pg 20

Front 24

Acute nephritic syndrome -- Post-strep GN

-LM
-IF
-EM

Back 24

LM: almost all of the capillary loops appear to be occluded by inflammatory cells (PMNs and monocytes) -- referred to as diffuse endocapillary proliferation.
IF: large, "lumpy-bumpy" granular peripheral capillary loop deposits; usually of IgG, C3, C1q and C4
EM: large, randomly spaced, subepithelial humps of immune complex type dense deposits

Hint 24

pg 21

Front 25

Acute nephritic syndrome -- Lupus nephritis

-clinical manifestations (4)

Back 25

1. Nephrotic syndrome - secondary
2. Acute nephritic syndrome
3. Asymptomatic hematuria/proteinuria
4. Frank acute renal failure - due to severe glomerular damage

Renal biopsy is usually required to gauge the activity of the inflammation and to quantify any chronic changes to the kidney

Hint 25

pg 21

Front 26

Acute nephritic syndrome -- Lupus nephritis

-proliferative changes

Back 26

--Mesangial proliferation - mesangial hypercellularity and increased matrix material

--Endocapillary proliferation - subendothelial deposits results in damage to the GBM - margination of cells within the capillary loops, necrosis and even rupture of the GBM may occur

Hint 26

pg 21/22

Front 27

Acute nephritic syndrome -- Lupus nephritis

-LM
-IF
-EM

Back 27

LM: mesangial hypercellularity, subendothelial deposits
IF: deposits positive for IgG, IgA, IgM, C3, and C1q -- "full house" effect
EM: "fingerprint" substructure in the deposits

Hint 27

pg 22

Front 28

Acute nephritic syndrome -- Lupus nephritis

-membranous changes

Back 28

Patients may have antibodies against podocyte surface antigens and develop the subepithelial deposits of membranous GN -- similar to idiopathic membranous GN

Hint 28

pg 22

Front 29

Asymptomatic Hematuria/Proteinuria -- IgA nephropathy (Berger's disease)

-epidemiology

Back 29

--most commonly affects children and young adults
--high incidence in southeast asians and native americans - most common primary GN in the world
--often history of upper respiratory or GI infection, or some other inflamed mucosal surface

Hint 29

pg 22

Front 30

Asymptomatic Hematuria/Proteinuria -- IgA nephropathy (Berger's disease)

-clinical presentation

Back 30

Patients present with a history of intermittent macroscopic hematuria, or hematuria/proteinuria are noted ona routine urinalysis

Hint 30

pg 22

Front 31

Asymptomatic Hematuria/Proteinuria -- IgA nephropathy (Berger's disease)

-diagnosis

Back 31

--mesangial deposition of complexes containing IgA and C3 on IF (no classical pathway components like C1q or C4).

Hint 31

pg 23

Front 32

Asymptomatic Hematuria/Proteinuria -- Alports Disease

-clinical presentation

Back 32

Patients present with varying degrees of:
1. Hematuria: most common presenting syndrome, usually microscopic and present in early childhood
2. High frequency hearing loss
3. Various occular defects which lead to increasing myopia and other visual changes

Hint 32

pg 23

Front 33

Asymptomatic Hematuria/Proteinuria -- Alports Disease

-pathogenesis

Back 33

--hereditary defect in Type IV collagen production (a component of the GBM)

--affects structures in the glomerulus, cochlea of the ear and certain eye structures

Hint 33

pg 23

Front 34

Asymptomatic Hematuria/Proteinuria -- Alports Disease

-LM
-IF
-EM

Back 34

LM: findings are nonspecific - glomeruli may appear to be normal or undergoing scarring
IF: not an immune complex disease, so routine IF is negative -- can be detected using newer techniques involving specially obtained anti-sera to various isoform chains of type IV collagen
EM: used to be the only method of diagnosis -- GBM is often thickened, characteristic lamellation or basket weave pattern.

Hint 34

pg 23

Front 35

Asymptomatic Hematuria/Proteinuria -- Thin basement membrane disease

-characterization of disease
-diagnosis

Back 35

--inherited disease, characterized by a defect in the GBM
--patients exhibit hematuria and proteinuria that may only be picked up on a routine physical
--most specific finding is abnormally thin GBM by EM (no other glomerular disease shares this characteristic)

Hint 35

pg 23

Front 36

Rapidly Progressive Glomerulonephritis (RPGN)

-definition

Back 36

-- may be caused by a number of different diseases which cause severe injury to the glomerulus

--histopathological hallmark is the crescent; a proliferation of cells within Bowman's space with resultant collapse of the glomerulus

Hint 36

pg 24

Front 37

Rapidly Progressive Glomerulonephritis (RPGN)

-- Type I - anti-GBM disease

Back 37

--may be associated with immune attack of the pulmonary capillary basement membrane with alveolar hemorrhage (Goodpasture's syndrome)
--antibodies to the GBM develop and damage the GBM severely
--bright, linear fluorescence of GBM for IgG is diagnostic

Hint 37

pg 24/25

Front 38

Rapidly Progressive Glomerulonephritis (RPGN)

-- Type II - immune complex mediated disease

Back 38

--any number of immune complex mediated diseases may cause RPGN when especially severe (SLE, post-strep GN, membranoproliferative GN and IgA nephropathy)
--important to diagnose these entities with kidney biopsy to allow for immediate treatment

Hint 38

pg 25

Front 39

Rapidly Progressive Glomerulonephritis (RPGN)

-- Type III - Pauci-immune disease (non-immune deposit or NID)

Back 39

--defined by the lack of finding of immune complexes or anti-GBM antibodies by IF and EM
--presence of serum antibody, ANCA in >90& of patients
--patients have circulating antibodies to components of the primary granules in neutrophils (myeloperoxidase and proteinase-3)

Hint 39

pg 25