Crr Week 8: Glomerular Disease (Kern)

Front 1

Structural abnormalities in the kidney can involve which 4 compartments?

Back 1

1. Glomeruli
2. Tubules
3. Interstitium
4. Blood vessels

*Disease of one compartment frequently effect the other compartments

Front 2

What are the 3 classifications of renal disease based on location?

Back 2

1. Pre-renal (decreased renal perfusion-- volume depletion, CHF)
2. Renal (diseases of the kidney itself)
3. Post-renal (obstruction of urinary tract)

*Clinical approach to acute renal insufficiency

Front 3

What is the most common cause of acute renal insufficiency?

Back 3

Pre-renal azotemia

*Usually not associated with structural damage, but if left untreated, can progress to Acute tubular necrosis

Front 4

What is the difference between primary and secondary renal disease?

Which is more common?

Back 4

Primary --> restricted to the kidney
Secondary --> systemic disease

*Secondary renal disease is more common

Front 5

Give 2 examples of congenital diseases that result in primary renal disease

Back 5

1. Alport syndrome (mutation in collagen Type IV)
2. Congenital nephrotic syndromes (mutations in nephrin and podocin)

Front 6

Which inherited syndrome results in tubular abnormalities (primary renal disease)?

Back 6

Fanconi's syndrome

Front 7

Do primary and secondary renal diseases have similar or different clinical presentations?

Back 7

Similar clinical presentations

Front 8

Do primary and secondary renal diseases have similar or different pathologic appearances?

Back 8

Same pathologic appearance

Front 9

What is the definition of azotemia?

By itself, is azotemia associated with any clinical conditions?

Back 9

Elevated urea nitrogen and creatinine

No. Azotemia is predominantly a biochemical abnormality. By itself, azotemia is NOT associated with any clinical symptoms

Front 10

What is the definition of uremia?

What are some symptoms involved?

Back 10

Symptom complex associated with impaired renal function

1. Altered mental status
2. Nausea and vomitting
3. Pericardial effusion (uremic pericarditis)

Front 11

What is uremia usually caused by?

Back 11

Significant, sustained renal impairment

Front 12

Which type of glomerulonephritis may present with the nephritic syndrome, nephrotic syndrome, or a mixture of both?

Back 12

Membranoproliferative glomerulonephritis (MPGN)

Front 13

List the 5 major clinical renal syndromes

Back 13

1. Acute glomerulonephritis (acute nephritic syndrome)
2. Proteinuria/nephrotic syndrome
3. Aysmptomatic hematuria
4. Acute renal failure
5. Chronic renal failure

Front 14

What is acute nephritic syndrome caused by?

Back 14

Acute glomerulonephritis-- inflammation in the glomerulus

Front 15

Which type of renal syndrome has active urine sediment, and what is the sediment composed of?

Back 15

Nephritic syndrome

1. Hematuria with dysmorphic RBCs
2. RBC casts
3. Proteinuria (mild to moderate)

Front 16

In Rapidly progress glomerulonephritis, how quickly does renal function decline?

Back 16

>50% decrease in GFR within 3 months

Front 17

Which type of glomerulonephritis is usually associated with crescents on renal biopsy?

Back 17

Rapidly progressive glomerulonephritis (RPGN)

*Goodpasture's syndrome

Front 18

What is the main difference between acute nephritis and RPGN?

Back 18

RAPID DECLINE in renal function seen in RPGN

Front 19

Which renal syndrome has relatively inactive urine sediment?

Back 19

Nephrotic syndrome

Front 20

What are some clinical manifestations of the nephritic syndrome?

Back 20

1. Mild-moderate proteinuria
2. Hypertension
3. Periorbital puffiness
4. Hematuria
5. RBC casts
6. Azotemia

Front 21

What are some clinical manifestations of the nephrotic syndrome?

Back 21

1. Severe proteinuria (>3.5 g/ 24 hours)
2. Generalized, pitting edema
3. Hypoalbuminemia
4. Hypercholesterolemia
5. Hypercoagulable state
6. Lipiduria with fatty casts

Front 22

Marked proteinuria seen in the nephrotic syndrome is usually of what origin?

Back 22

Glomerular in origin

Front 23

In the nephrotic syndrome, how is GFR changed?

Back 23

GFR is usually NORMAL in the nephrotic syndrome
(do not present with hypertension or azotemia)

*This differs from the nephritic syndrome, in which GFR is decreased from inflamed glomeruli

Front 24

List some renal diseases which present with the nephrotic syndrome.

Back 24

1. Minimal change disease
2. Focal segmental glomerulosclerosis
3. Membranous nephropathy
4. Membranoproliferative glomerulonephritis (MPGN)
5. Diabetic nephropahty
6. Amyloidosis

Front 25

List some renal diseases which present with the nephritic syndrome.

Back 25

1. IgA glomerulopathy (Berger's disease)
2. Post-streptococcal glomerulonephritis
3. Diffuse proliferative glomerulonephritis (SLE)
4. Rapidly progressive glomerulonephritis

Front 26

How does asymptomatic hematuria affect the GFR?

Back 26

GFR is usually not affected.
(not associated with edema or hypertension)

Front 27

What is the most common type of tubular disease that causes acute renal insufficiency?

Back 27

Acute tubular necrosis

Front 28

Which tubular change is most commonly associated with chronic renal failure?

Back 28

Tubular atrophy

Front 29

What are the 2 classes of Acute tubular necrosis?

Back 29

1. Ischemic
2. Toxic

Front 30

What usually causes acute pyelonephritis?

Back 30

Acute infection, usually caused by bacteria in the bladder ascending up the ureter into the kidney

Front 31

List 3 tubular diseases.

Back 31

1. Acute tubular necrosis
2. Tubular atrophy/scarring
3. Pyelonephritis

Front 32

List 3 interstitial diseases of the kidney.

Back 32

1. Acute interstitial nephritis
2. Chronic interstitial nephritis
3. Interstitial fibrosis

Front 33

List 4 vascular diseases that result in renal injury

Back 33

1. Vasculitis
2. Embolization
3. Hypertension
4. Vascular sclerosis

Front 34

The glomerular capillaries are surrounded by which layer of bowman's capsule?

Back 34

Visceral epithelium (podocytes)

Front 35

What are the glomerular capillaries held together by?

Back 35

Mesangium
(composed of mesangial cells and mesangial matrix)

Front 36

Which layer of bowman's capsule forms the inner-lining of the capsule?

Back 36

Parietal epithelial cells

(Visceral epithelial cells directly surround the glomerular capillaries)

Front 37

List 3 lab methods of studying glomerular diseases.

Which method is always critical?

Back 37

1. Light microscopy (H&E and special stains) <--CRITICAL
2. Immunofluorescence
3. Electron microscopy

Front 38

What is the difference between focal and diffuse glomerular disease?

Back 38

Focal --> only some glomeruli affected
Diffuse --> most or ALL glomeruli affected

*Relates to NUMBER of glomeruli

Front 39

What is the difference between segmental and global glomerular diseae?

Back 39

Segmental --> just PART of the glomerulus is involved
Global --> ENTIRE glomerulus involved

*Relates to how much of each glomeruli is involved

Front 40

What is the difference between intracapillary and extracapillary proliferation?

Back 40

Intracapillary --> accumulation of cells WITHIN glomerular capillary tuft
Extracapillary --> accumulation of cells in urinary (Bowman's) space. Typically called "crescents"

Front 41

What kind of capillary proliferation results in "crescents"?

Back 41

Extracapillary proliferation

Front 42

What type of capillary proliferation is a marker of SEVERE glomerular injury?

What causes this?

Back 42

Extracapillary proliferation

*Ruptures in glomerular capillary basement membrane allows fibrin to leak into Bowman's space--> stimulates proliferation of the parietal epithelial cells--> recuirtment of monocytes

Front 43

Extracapillary proliferation often results in which renal disease?

Back 43

Rapidly progressive glomerulonephritis (RPGN)

Front 44

List 4 mechanisms of glomerular injury

Back 44

1. Immune-mediated (Ab, complement, leukocytes)
2. Metabolic
3. Hemodynamic (hyperperfusion)
4. Vascular (vasculitis, thrombosis, embolism)

Front 45

How does glomerular injury caused by hyperperfusion manifest pathologically?

Back 45

Manifests as Focal segmental sclerosis

Front 46

What are the various etiologies of glomerular diseases?

Back 46

1. Infectious
2. Ab against tissue antigens (DNA, proteins)
3. Autoimmune diseases
4. Intravascular coagulation/thrombosis
5. Metabolic factors
6. Neoplasms
7. Drugs/chemical agents
8. Physical/mechanical factors
9. Genetic factors

Front 47

Which infections most commonly cause glomerular disease?

Back 47

1. Bacteria (S. pyogenes, S. aureus)
2. Viruses (Hep B, C)

Front 48

Mutations in intrinsic glomerular proteins (nephrin, podocin), results in which genetic syndrome?

Back 48

Congenital nephrotic syndrome

Front 49

Are most cases of hematuria causes by glomerular disease or extra-renal diseases?

Back 49

Extra-renal
(usually diseases of the ureters or bladder)

Front 50

The finding of dysmorphic RBCs or RBC casts in the urine is proof of what?

Back 50

Glomerular hematuria (as opposed to hematuria from other sites of the urinary tract)

*RBC casts are characteristic of the nephritic syndrome

Front 51

List 2 types of fixed tissue antigens that are involved in Ab-mediated glomerular injury

Back 51

1. Goodpasture's antigen: Anti-GBM nephritis
2. Podocyte antigens: Membranous GN

*Fixed tissue antigens are antigens that are intrinsic to the glomerulus

Front 52

Give 2 examples of planted antigens involved with Ab-mediated glomerular injury

Back 52

1. Endogenous antigens (DNA, tumor)
2. Exogenous antigens (microbial, drugs)

*Planted antigens are things that were in the circulation and deposits in the kidney. THEN the antibody reacted with the antigen.

Front 53

Where are the 4 main locations in glomeruli that Ab or Ab-antigen complexes can deposit?

Back 53

1. Along GBM itself
2. Subepithelial (B/w GBM and foot processes)
3. Subendothelial (b/w GBM and endothelial cells)
4. Mesangium

Front 54

Which type of Ab deposit in the subepithelial space?

Back 54

(area between GBM and foot processes)

1. Ab w/ intrinsic podocyte antigens
2. Antigens that have crossed the GBM and deposited in the subepithelial space

Front 55

In which space do circulating immune complexes tend to deposit, if they can cross the GBM?

Back 55

Subepithelial space

Front 56

Where do immune complexes tend to deposit if they are too large to cross the GBM?

Back 56

Mesangium

Front 57

Which type of deposits are associated with significant inflammation, intracapillary proliferation, and tend to be more damaging to the glomerulus?

Does this cause the nephritic or nephrotic syndrome?

Back 57

Subendothelial deposits
*Nephritic syndrome with hematuria

Front 58

Do subepithelial deposits usually cause significant inflammation?

Back 58

No.
(they usually manifest clinically as proteinuria)

Front 59

Which type of deposits tend to cause hematuria, but usually not with marked acute decrease in renal function?

Back 59

Mesangial deposits

Front 60

Which type of deposits are associated with severe glomerular injury with crescents in Bowman's space?

Back 60

GBM

Front 61

Which glomerular disease results in subepithelial "humps"?

Back 61

Post-streptococcus glomerulonephritis

Front 62

Which glomerular disease results in subepithelial epimembranous deposits?

Back 62

Membranous nephropathy

Front 63

Which glomerular diseases result in subendothelial granular deposits?

Back 63

1. Diffuse proliferative glomerulonephritis (SLE)
2. MPGN I

Front 64

Which glomerular disease results in mesangial deposition?

Back 64

Focal Segmental Glomerulosclerosis

Front 65

In rapidly progressive glomerulonephritis, where would antibody deposits be found?

Back 65

Along the glomerular basement membrane
(linear pattern)

Front 66

Which disease is often associated with pulmonary hemorrhage?

Back 66

Anti-GBM disease
(Goodpasture's diseae)

Front 67

Which 2 glomerular diseases result in deposits between podocytes and GBM?

Back 67

(subepithelial)

1. Post-infectious GN
2. Membranous GN

Front 68

Which 2 glomerular diseases result in deposits between GBM and endothelium?

Back 68

(subendothelial)

1. SLE
2. MPGN

Front 69

Which glomerular disease results in mesangial deposits?

Back 69

IgA nephropathy

Front 70

Which type of deposits cause injury to foot processes?

Back 70

Subepithelial deposits

Front 71

Which type of deposits result in an inflammatory response-- subendothelial or supepithelial?

Back 71

Subendothelial
(exposed to circulation)

*Inflammation, hematuria (nephritic syndrome)

Front 72

Which type of deposits result in greater proteinuria-- subendothelial or subepithelial?

Back 72

Subepithelial

Front 73

List 3 acute nephritic syndromes

Back 73

1. Post-infectious GN
2. MPGN
3. Lupus nephritis
4. IgA nephropathy (sometimes)

Front 74

List 3 rapidly progressive GN diseases

Back 74

1. Anti-GBM disease (Goodpasture's)
2. ANCA-associated GN (Microscopic polyangiitis or Wegener's granulomatosis)
3. Immune complex GN (severe)

Front 75

List 3 types of asymptomatic hematuria diseases

Back 75

1. IgA nephropathy
2. Alport syndrome
3. Thin GBM nephropathy

Front 76

Post-streptococcal GN usually occurs in which individuals?

Back 76

Children and young adults

Front 77

When does post-streptococcal GN usually occur following pharyngitis?

Back 77

1-2 weeks following pharyngitis

Front 78

Describe the clinical picture of post-streptococcal GN.

Back 78

Abrupt onset of:
1. "smoky" urine
2. Edema
3. Hypertension
4. +/- oliguria
5. Hematuria, RBC casts
6. Low serum complement levels

Front 79

Which antibodies will be elevated in post-streptococcal GN?

Back 79

Ab against streptolysin O (ASO), and DNase-B

Front 80

What is the classical appearance of post-streptococcal GN, viewed by light microscopy?

Back 80

Diffuse, global, proliferative intracapillary GN.
*Often with neutrophils present

Front 81

Are crescents seen in post-streptococcal GN?

Back 81

Only in the more severe cases

Front 82

Which Ab and complement proteins compose the deposits resulting from post-infectious GN?

Back 82

IgG and C3

Front 83

What are the 2 types of MPGN?

Back 83

1. Type I (most common)
2. Type II (dense deposit disease)

Front 84

Adult cases of Type I MPGN are usually caused by?

Back 84

1. Hep C virus
2. Cryoglobulinemia

Front 85

Pediatric cases of Type I MPGN are usually caused by?

Back 85

???
Idiopathic

Front 86

What are some causes of Type I MPGN?

Back 86

1. *Idiopathic
2. *Hepatitis C (often with cryoglobulins)
3. Other infections
4. Autoimmune diseases

Front 87

Reduplication of GBM ("track track") is a key feature of which glomerular disease?

Where is this new layer located?

Back 87

MPGN

*Located inside the original basement membrane

Front 88

What is the clinical course of Type I MPGN?

Back 88

1/3: Remission
1/3: Slow progression to chronic renal insufficiency
1/3: Waxes and wanes, but never disappears

Front 89

What is the treatment for MPGN?

Back 89

MPGN secondary to other diseases --> treat the underlying disease

Idiopathic MPGN--> immunosuppressants

Front 90

Activation of _________ is critical in the pathogenesis of MPGN.

Back 90

Complement system

Front 91

Which disease involves the activation of the alternative pathway of complement activation?

Which autoantibody is involved?

Back 91

Dense deposit disease (MPGN Type II)
*C3 nephritic factor antibody (bind to and prevents inactivation of C3 convertase)

*Results in prolonged activation of alternate pathway of complement

Front 92

Dense linear deposits WITHIN thickened GMB is a characteristic feature of which glomerular disease?

Which type of microscopy is used to see this feature?

Back 92

Dense deposit disease (MPGN Type II)

*Electron microscopy

Front 93

How are the locations of deposits different in Type I and Type II MPGN?

Back 93

Type I --> deposits are BENEATH the GBM (subendothelial)
Type II --> deposits are WITHIN the GBM

Front 94

What is the cause of Dense deposit disease?

What is the clinical course?

Back 94

Cause is unknown

Majority of cases progress to CRF

Front 95

In RPGN >____% of glomeruli have crescents.

Back 95

>50%

Front 96

List 3 main pathophysiologic causes of RPGN (crescentic GN).

Back 96

1. Anti-GBM diseases
2. ANCA-associated GN
3. Immune complex type (usually infectious-- severe cases of post-strep GN)

Front 97

Which individuals are typically affected by Goodpasture's syndrome?

Back 97

Bimodal age distribution--> 20s and 50s
(slight male predominance)

Front 98

In Goodpasture's syndrome, which part of the GBM is attacked by Ab?

Back 98

Usually part of collagen IV

Front 99

What is the treatment for Anti-GBM disease?

Back 99

1. Plasmapheresis
2. Corticosteroids
3. Cyclophosphamide

*Majority of patients recover with this treatment

Front 100

What is the usual cause of death in the acute phase of Anti-GBM disease?

Back 100

Pulmonary hemorrhage

Front 101

What is the most common cause of RPGN?

Back 101

ANCA-associated GN

Front 102

Which type of glomerulonephritis is usually "pauci-immune"?

Back 102

ANCA-associated RPGN

*Very characteristic! Immunofluorescence is NEGATIVE; no Igs or complement are detected

Front 103

List 2 antibodies associated with RPGN.

Back 103

1. PR3-ANCA (c-ANCA) --> Wegener's granulomatosis
2. MPO-ANCA (P-ANCA) --> Microscopitc polyangiitis

Front 104

Does ANCA-associated RPGN result in segmental or global glomerular necrosis?

Back 104

Segmental

Front 105

RPGN Associated with immune complexes can result from which infections?

Back 105

1. Endocarditis
2. Deep visceral abscesses
3. Shunt infection
(others)

Front 106

Does diabetic nephropathy usually present as the nephritic or nephrotic syndrome?

Back 106

Nephrotic syndrome

*Diabetes is probably the most common cause of the nephrotic syndrome overall

Front 107

Does amyloidosis usually present as the nephritic or nephrotic syndrome?

Back 107

Nephrotic syndrome

Front 108

What are the 2 most common nephrotic syndrome diseases seen in children?

Back 108

1. Minimal change disease
2. Focal segmental glomerulosclerosis

Front 109

What are the 2 most common nephrotic syndrome diseases seen in adults?

Back 109

1. FSGS
2. Membranous nephropathy

Front 110

What is the most common cause of nephrotic syndrome in African Americans?

Back 110

FSGS

Front 111

What is the peak age of onset for minimal change disease?

Back 111

3 - 4 years
(in children, there is a strong male predominance)

Front 112

What is the cause of most cases of minimal change disease?

Back 112

UNKNOWN

*But some cases are secondary to Hodgkin lymphoma or medications (NSAIDs)

Front 113

Describe the laboratory picture of Minimal change disease (light microscopy, IF, and electron microscopy findings).

Back 113

Light microscopy--> Essentially normal glomeruli
Immunofluorescence --> Negative
Electron microscopy --> Diffuse effacement of visceral epithelial cell foot processes

Front 114

Diffuse "effacement" of visceral epithelial cell foot processes seen on electron microscopy is indicative of which glomerular disease?

Back 114

Minimal change disease

Front 115

What is the primary treatment for minimal change disease?

What is the prognosis in children and adults?

Back 115

Corticosteroids

Prognosis in children is good
Response in adults is less favorable

*Response to corticosteroids is part of clinical diagnostic criteria for idiopathic minimal change disease in children

Front 116

HIV is associated with which glomerular disease?

Back 116

FSGS
*"collapsing glomerulonephropathy"

Front 117

Are immune complex deposits present in FSGS?

Back 117

No

Front 118

What is the treatment for FSGS?

Back 118

1. Corticosteroids (some response-- only 15-30%)
2. Cyclophosphamide
3. Cyclosporine

Front 119

What is the most common PRIMARY renal cause of nephrotic syndrome in adults?

Back 119

Membranous nephropathy

*GOLJAN says FSGS is 1st, and membranous nephropathy is 2nd

Front 120

Which nephrotic syndrome disease is often associated with carcinomas?

Back 120

Membranous nephropathy
(lung, colon, breast, and kidney carcinomas)

Front 121

Thickening of the GBM with GBM "spikes" is characteristic of what glomerular disease?

Back 121

Membranous nephropathy

Front 122

What is the difference between the deposits that form in membranous nephropathy and post-infectious GN?

Back 122

(Both form subepithelial deposits)

Membranous nephropathy --> deposits are numerous, relatively small, and distributed more or less evenly over the entire glomerular capillary

Post-infectious GN --> deposits are much larger ("humps"), relatively rare, and irregularly distributed.

Front 123

What is the treatment for membranous nephropathy?

Back 123

(Treatment is not well established)
1. Corticosteroids +/- cylcophosphamide
2. ACEI, ARBs to reduce proteinuria

Front 124

Which 3 glomerular diseases present with asymptomatic hematuria?

Back 124

1. IgA nephropathy (Berger's disease)
2. Alport syndrome
3. Thin basement membrane nephropathy

Front 125

What is the most common type of primary glomerulonephritis worldwide?

Back 125

IgA nephropathy (Berger's disease)

Front 126

Which glomerular disease has the same IF features as those seen with Henoch-Schonlein purpura (HSP)?

Back 126

IgA nephropathy

*IgA deposits in mesangium

Front 127

Describe the Henoch-Schonlein purpura (HSP) clinical syndrome.

Back 127

Systemic vasculitis effecting GI tract, skin, and joints

1. Abdominal pain
2. Arthritis
3. Glomerulonpehritis
4. Skin rash

Front 128

Why might there be defective clearance of IgA molecules from circulation in IgA nephropathy?

Back 128

Abnormality in hinge region of IgA may result in defective clearance

Front 129

Does IgA nepropathy result in focal or diffuse proliferation? Segmental or global?

Back 129

Focal segmental

Front 130

What is the typical presentation of IgA nephropathy?

Back 130

Hematuria
(maybe occurring a few days after an upper respiratory tract infection)

Front 131

Which glomerular disease results in episodic bouts of hematuria (gross of microscopic), usually following an upper respiratory tract infection?

Back 131

IgA nephropathy

Front 132

Which glomerular disease can be associated with HBV or malaria?

Back 132

Membranous glomerulonephropathy

Front 133

What is the clinical course of IgA nephropathy?

Back 133

Variable

1. Some go into remission
2. Some have persistent microscopic hematuria and proteinuria, but preserved renal function
3. Some progressively decline to CRF

Front 134

What is the treatment for IgA nephropathy?

Back 134

No specific therapy

1. Supportive care (control BP and reduce proteinuria with ACEI and ARBs)
2. Immunosuppressives in patients with acute course
3. Fish oil

Front 135

What is the most important difference between Henoch-Schonlein Purpura and IgA nephropathy?

Back 135

HSP is a systemic disease (vasculitis)
IgA nephropathy is limited to the kidney

Front 136

Henoch-Schonlein purpura is most common in which age group?

Back 136

Children (3 - 8 years)

*HSP is more common in young children, IgA nephropathy is more common in older children and adults

Front 137

Does Henoch-Schonlein Purpura usually have a good prognosis or a poor one?

Back 137

Very good prognosis
(especially in children; however, it is less favorable in adults)

Front 138

Alport syndrome involves a mutation in which molecule?

Back 138

alpha-5 chain of Type IV collagen (important component of the GBM)

*GBM develops a "basket wave" appearance

Front 139

At what age does the onset of Alport syndrome typically occur?

What is the clinical presentation?

Back 139

Onset: ~5 - 20 yo

Presents as hematuria +/- proteinuria

Front 140

Alport syndrome is also associated with which 2 types of disorders?

Back 140

Hearing loss and eye disorders

Front 141

What is the inheritance pattern of Alport syndrome?

How are males and females affected?

Back 141

Majority are X-linked
(some are autosomal recessive, and rarely autosomal dominant)

For x-linked inheritance:
*Males have progression to renal insufficiency
*Female carriers have hematuria, and usually do not progress to renal insufficiency

Front 142

What is the inheritance pattern of thin basement membrane nephropathy?

What is the mutation?

Back 142

Autosomal dominant

*Mutation in type IV collagen subunit (different part than in Alport's)

Front 143

What is the morphology of chronic glomerulonephritis?

Back 143

Global glomerulosclerosis, involving majority of glomeruli