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CPR Exam 2 > Chapter 20.1: Glomerulonephropathies > Flashcards

Chapter 20.1: Glomerulonephropathies Flashcards

1
Q

Nephritic Syndrome

Process and Sx

A
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2
Q

Nephritic Syndrome

Glomerular diseases presenting with nephritic syndrome are often characterized by ________________ => nephritis, damaging the filtration barrier to __________

  • Features: _______, ___________ (<3.5 grams/day), ______, ____; usually sicker/less sick than nephrotic
A

Glomerular diseases presenting with nephritic syndrome are often characterized by inflammation in the glomeruli => nephritis, damaging the filtration barrier to RBC and proteins.

  • Features: Hematuria, mild proteinuria (<3.5 grams/day), azotemia, HTN; usually sicker than nephrotic
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3
Q

Major causes of Nephritic Syndrome

A
  1. Acute/Diffuse proliferative (post-streptococcal) glomerulonephritis
  2. RPGN
  3. Berger’s IgA nephropathy
  4. Alport Syndrome
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4
Q

Acute (Diffuse) Proliferative Glomerulonephritis is a _______ syndrome and is a __________ hypersensitivity reaction.

A

Nephritic

Type 3 (Immune complex)

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5
Q

Acute (Diffuse) Proliferative Glomerulonephritis is what, that typically occurs when, in who?

A
  • Inflammation of the glomeruli after group A B-hemolytic strep infection in children and young adults, but may occur after infection with many other organisms. Usually FTER,
    • Impetigo (skin)
    • Pharyngitis (strep)
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6
Q

Strep can lead to rheumatic fever and post-strep GN.

Can patients develop both?

A

No.

  • Certain strep bacteria are nephritogenic strains, which are specific types of M protein virulence factor.
    • Subtype: lancefield group A.
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7
Q

What is the pathology of Acute (Diffuse) Proliferative Glomerulonephritis?

Group A B-Hemolytic Strep causes?

How do lesions form?

A
  • 1-4 weeks AFTER Group A B-hemolytic strep => causes diffuse proliferation of glomerular cells and influx of leukocytes in all glomeruli
  • Lesions formed when:
    • [IgG/M Ab] against [step pyogenic exotoxin B (SpeB)] antigen =>
    • in-situ formation of immune-complexes in the subepithelium (with many neutrophils).
      • => inflammatory reaction, which involves + compliment (C3) and attracts PMNs, which damage podocytes
      • Leads to hypocomplementemia, because it degrades the body of compliment proteins.
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8
Q

In acute proliferative glomerulonephritis, in-situ immune complexes that form in _________ spaces will do what?

A
  • Subepithelial
  • => inflammation => + compliment & attract PMNS =>
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9
Q

Acute (Diffuse) Proliferative Glomerulonephritis

  • Light microscopy:
  • Electron microscopy:
  • IF:
A
  • Light Microscopy: Hypercellular & enlarged glomeruli (d/t proliferation of endothelial/mesangial cells) and many leukocytes (d/t inflammation)
    • Not specific
  • Electron Microscopy: Subepithelial humps of immune complexes
    • DIAGNOSTIC of POST-STREP GN
  • Immuno-Fluorescence: “starry sky”; granular deposits of IgG, IgM and C3 in mesangium and along GBM
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10
Q

Acute (Diffuse) Proliferative Glomerulonephritis is most common in who?

A

Children (6-10); more atypical and aggressive in adults

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11
Q

How is acute proliferative GN different in children and adults

A
  • More atypical and aggressive in adults => causes sudden HTN, edema, high BUN
  • Recovery
    • 95% recovery in children; 60% recovery in adults
  • Takes adults longer to heal
  • More progress to chronic glomerulonephritis or RPGN type 2(10%)
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12
Q

Acute/diffuse proliferative GN is most likely to occur in children (6-10) ___________ after a strep throat/skin infection (impetigo) due to ab to ________.

A
  • 1-4 weeks (thus, pt will have no sx)
  • SpeB (streptococcal pyogenic exotoxin B)
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13
Q
  • How does Acute Proliferative (Poststreptococcal) Glomerulonephritis typically present (signs/sx’s and findings)?
  • Urine?
A
  • 1-4 weeks AFTER infection, child (6-10 YO) will have fatigue + fever + nasuea + oliguria + hematuria and sx of nephritic syndrome
  • Urine: red cell casts, dysmorphic RBCs
    *
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14
Q

Blood tests of patient with acute proliferative (post-strep) glomerulonephritis will have what findings?

A
  • + ASO titers for Strep (Antistreptolyosin O Ab), anti-DNaseB
  • low compliment levels
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15
Q

What is the outcome of children with Acute (Diffuse) Proliferative Glomerulonephritis d/t strep?

A
  • 95% recover w/ conservative therapy (water and salt restriction) (<1% progress to RPGN Type II)
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16
Q
  • Acute proliferative GN does not have to occur d/t strep => Acute proliferative glomerulonephritis (post-infectious and non-streptococcal) can occur d/t what else?
A
  • 1. Bacteria
  • 2. Viral
  • 3. Parasites (toxoplasmosis and malaria)
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17
Q

How do the immune deposits found in postinfectious GN due to staphylococcal infection differ from that of strep?

A
  • immune deposits have IgA, not IgG
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18
Q
  • NOTE: Distractor! if there is a current complaint of sore throat and dry cough it is what can we exclude
A

PSGN: happens 1-4 weeks after an untreated case

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19
Q

Rapidly Progressive Glomerulonephritis (RPGN) is a _______ syndrome and a __________ hypersensitivity reaction.

A

Nephritic

Type 2 (immune complex)

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20
Q

What is Rapidly Progressive Glomerulonephritis (RPGN)?

A
  • A severe form of glomerulonephritis where inflammation can lead to renal failure in weeks - months
  • Caused by:
    • Cell-mediated immune response and MO cause BM to tear
      • RBC, inflammatory mediatorys (=> inflammation) plasma proteins, fibrin, monocyte/MO & parietal epithelial cells leak out into Bowmans space =>
      • Parietal epithelial cells, MO/monocytes, fibrin & thrombin** => formation of **crescents in Bowmans space (causing normally thin epithlial layer to thicken and necrosis.
        *
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21
Q

What makes up crescents in RPGN?

How do we view them?

A
  • Proliferation of parietal epithelial cells that line Bowman’s capsule, monocytes, MO, and fibrin
  • PAS stain on LM
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22
Q

What occurs due to the damage induced in RPGN?

A
    1. Rapid obliteration of urinary space => rapid and progressive loss of renal function,
    1. Severe oligaria
    1. Tears in BM => cause RBCs to squeeze throuhh and NTR urinary space => hematuria
    1. Renal failure in weeks to months
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23
Q

What symptoms can we see in a patient that we suspect has RPGN before conducting a renal biopsy?

A

1. Nephritic urine (RBC in urine)

2. Fatigue and anorexia

3. Acute renal failure

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24
Q

Causes of RPGN are distinguished based on what?

A

IMMUNOFLUORESCNCE​

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25
Q

What do we see on LM, EM in a patient with RPGN?

A
  • Light microscopy: Crescents & MO/leukocyte infiltration
  • Electron microscopy: wrinkling/tearing of GBM and RBC can often be seen scooting into urinary space
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26
Q

Causes of RPGN are distinguished based on immunofluorescence.

How do we do so?

A
  1. RPGN Type 1: Linear IF
  2. RPGN Type 2: Granular IF
  3. RPGN Type 3: Negative IF
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27
Q

RPGN Type 1 (______)

RPGN Type 2 (______)

RPGN Type 3 (______)

A

RPGN Type 1 (anti-GBM)

RPGN Type 2 (Immune complex)

RPGN Type 3 (Pausi-immune)

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28
Q

Type I RPGN (anti-GMB Ab) disease is characterized by what kind of deposits?

Why this pattern?

A
  • Linear deposits of anti-GM antibodies (IgG and C3) in the GBM of kidney and lung.
    • Linear bc binds to intrinsic Ag along ENTIRE length of GBM
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29
Q
  • RPGN Type I (Anti-GBM Antibody) occurs when…
A
  • anti-GBM antibodies against GBM antigens deposit in the BM
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30
Q

_______ is an example of a disorder than can cause RPGN Type I (anti-GBM Ab).

A

Goodpastures

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31
Q

Goodpastures syndrome can cause RPGM Type 1 (anti-GBM Abs).

What antigen will the anti-GBM Abs attack?

A
  • [non-collagen portion of a-3 chain of type 4 collagen] in the GBM and alveoli
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32
Q

RPGN Type 1 that occurs in Goodpastures syndrome causes what symptoms?

A
  1. Hemoptysis due to pulmonary hemorrhage
  2. Hematuria
  3. Nephritic syndrome
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33
Q

Which HLA subtype is associated an increased liklihood of getting RPGN (i.e., Goodpasture Syndrome)?

A

HLA-DRB1

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34
Q

What is used in the treatment for Type I RPGN (anti-GBM Ab disease)?

How effective?

A
  • Plasmapheresis + immunosupressive therapy
  • Can reverse pulmonary hemoorhage and renal failure
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35
Q
  • Type 2 RPGN (immune complex mediated) disease is characterized what pattern of IF?
  • Where do the immune complexes deposit?
A

Subendothelial Granular due to deposition of immune complex

& cell proliferation

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36
Q

Major causes of Type II (immune complex) RPGN?

A

Occurs due to the progression of

  1. Post-infection GN (post-strep acute proliferative GN)
  2. SLE
  3. IgA Nephropathy
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37
Q

RPGN Type 2 (Immune complex) is a type ____ hypersensitivity reaction.

ignore until further notice.

A

3

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38
Q

Can Type II RPGN be treated by plasmapheresis?

A

No; treat underlying disease

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39
Q

Type 3 RPGN disease is characterized by what kind of deposits?

A
  • NO [anti-GBM Ab & immune complexes] because of a pausi-immune response.
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40
Q

Presence of what in the serum is virtually diagnostic of Type III (Pauci-Immune) RPGN?

A

p/c-ANCA (anti-neutrophil cytoplasmic Ab)

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41
Q

Type III (Pauci-Immune) RPGN may occur due to underlying disorders?

A
  • Vasculitis syndromes, such as
      1. Wegener (c-ANCA)
      1. Microscopic Polyangiitis and Churg Strauss (pANCA)
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42
Q

In RPGN what is commonly seen in prominent amounts between the cellular layers in crescents?

A

Fibrin

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43
Q

Rapidly progressive glomerulonephritis can evolve into _________ or lead to what?

A
  • Chronic glomerulosclerosis**
  • Renal failure in weeks => months
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44
Q

In nephrotic syndrome, what barrier is lost?

A

Barrier to proteins (podocytes/epithlielial cells); RBC filtration barrier (endothelium) is intact.

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45
Q
  • Most causes of nephrotic syndrome are related to damage of what?
A
  • Podocytes (epithelial cells) => protein loss only
  • Endothelial cells (RBC barrier) are intact
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46
Q

Does inflammation occur in nephrotic syndromes?

A

NO

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47
Q

What causes nephrotic syndrome, resulting in proteinuria?

And if indicated, what are they due to?

A
  1. Primary
    1. Minimal change disease: cytokines
    2. Focal segmental glomerulosclerosis (FSGS): podocyte damage
    3. Membranous nephropathy: immune complexes
      1. Diabetic: glucose
  2. Systemic causes
      1. Membranoproliferative glomerulonephritis
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48
Q

Nephrotic syndrome in US kids less than 17YO is due to what?

A

To primary lesion of the kidney

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49
Q

What primary lesion is most common in children?

A

Minimal change disease (75% of cases in children)

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50
Q

How does the cause of nephrotic syndrome in children <17 yo differ from adults?

A
    • Children = almost always caused by a lesion primary to the kidney
    • Adults = often associated with a systemic disease
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51
Q

What are the 3 most common primary glomerular lesions responsible for the development of nephrotic syndrome?

Which is most common in children and which in adults?

A
  1. Minimal change disease = most common in children (75%)
  2. Membranous glomerulopathy = most common in older adults
  3. Focal segmental glomerulosclerosis = occurs at all ages
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52
Q

What are the most frequent systemic causes of nephrotic syndrome?

A
  1. - Diabetes
  2. - Amyloidosis
  3. - SLE
    • Drugs
    • Infections
    • Malignant dz (carcinoma, lymphoma)
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53
Q

How should we treat nephrotic syndrome in children?

A
  • Nephrotic syndrome in children is minimal change disease** until proven otherwise; **don’t biopsy – tx with steroids and see if condition improves because MCD responds to steroids.
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54
Q

In one word, what is the cause of

  • 1. Minimal Change Disease
  • 2. Focal Segmental Glomerulosclerosis
  • 3. Membranous Nephropathy
A
    1. Minimal Change Disease
      * ​Cytokines
    1. Focal Segmental Glomerulosclerosis
      * Podocyte damage
    1. Membranous Nephropathy
      * Immune complexes
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55
Q

What does the term “nephrotic range proteinuria” refer to?

A

Loss of 3 grams or more/day in the urine

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56
Q
  • ___________ is the 2nd most common cause of nephrotic syndrome in adults (30%)
A

Membranous Glomerulopathy (nephropathy)

FSGS (35%) is most common.

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57
Q

What is membranous nephropathy?

A
  • Chronic immune-complex mediated disease that causes diffuse thickening of the glomerular BM (without hypercellarity) due to deposits of IgG on subepithelial side of the BM.
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58
Q

Most causes of membranous glomerulopathy are primary/secondary

A

Primary (75% of cases)

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59
Q

Primary membranous glomerulopathy is now considered an autoimmune disease and linked to which HLA allele?

A

HLA-DQA1

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60
Q

Primary membranous glomerulopathy is a diffuse thickening of the glomerular BM (without hypercellarity). How does this happen?

A
  • IMMUNE COMPLEXES:
    1. autoAB to phospholipase A2 receptor (PLA2R) antigens (or neutral endopeptidase in secondary) on the podocytes => form subepithelial immune complex deposits (primarily IgG4)
    2. => Leukocyte infiltration and activate compliment =>
      1. MAC causes capillary wall to become leaky => proteins leave
      2. Damage to podocytes and mesengial cells => effacement
    3. Overtime, podocytes lay extra BM => thickening of BM (but no hypercellularity) between immune complexes=> creating a spike and dome appearance
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61
Q

How is Membranous Glomerulopathy different from Minimal Change Disease?

A
  • Membranous Glomerulopathy does NOT respond to steroid therapy.
  • MCD does.
62
Q

What appearance does membranous glomeruleropathy create?

A
  • Spike and dome appearance due to thickening of glomerular BM (but no hypercellularity).
63
Q

If thickening of the BM occured + hypercellularity, what nephropathy would this be?

A

Membranoproliferative glomerulonephritis

64
Q

Membranous glomerulonephropathy

    1. LM
    1. EM
    1. Immunoflourescence
A
  1. LM: Uniform, diffuse thickening (no hypercellularity) of BM on PAS stain
  2. EM:
  • [Spike and dome pattern]: subepithelial deposits of IgG4 on silver stain
  • [Effaced (Flattened) foot processes]
  1. IF: “Lumpy bumpy” IgG4 granular deposits
65
Q

What are some of the secondary causes of Membranous Nephropathy?

A

“TUMOR, HEPATITIS, RHEUMATOID ARTHRITIS”

  • 1. Drugs used to tx RA
  • 2. Malignancies
  • 3. Infections (hepB/C)
  • 4. SLE, Autoimmine disorders
66
Q

Secondary membranous glomerulonephritis is more likely to experience _______.

A

Hematuria

67
Q

Describe the proteinuria experienced in membranous glomerulopathy

A

Non-selective

68
Q

Recurrence of Membranous Nephropathy is a common feature in which patients?

A

1. Transplant pts for end-stage renal disease

  1. Women have spontaneous remissions and more benign outcome
69
Q

What is the prognosis of membranous glomerulonephropathy in children?

What can MGN result in?

A
  • Good prognosis in children
  • 60% of pts => proteinuria persists
  • 40% => renal insufficiency
  • 10% => ESRD
70
Q

How is minimal change disease different from membranous glomerulonephropathy in regards to the proteins that leak out?

A
  • Minimal change disease: selective proteinuria (only albumin)
  • Membranous glomerulonephropathy: non-selective proteinuria (albumin AND Ig)
71
Q

Minimal change disease is also called _________.

A

Nil disease.

72
Q

What is minimal change disease?

How does it occur?

A

Nephrotic syndrome where foot processes of the podocytes are damaged, allowing albumin to leak out of the capillary => urinary space.

  • MOA:
      1. T-cells release cytokines,
      1. Damage
        * damage the (-) charge on podocytes
        * effacement (flatten & fusion of) foot processes
      1. Selective proteinuria
      1. (-) charged albumin leaks out => ↑ albumin in the urine => nephrotic syndrome
73
Q

Minimal Change Disease

  1. LM
  2. EM
  3. Immunoflourescence
A

FINDING ONLY ON EM!

    1. LM: NL
    1. Immunofluorescence: NL bc damage is d/t cytokines
    1. EM: Effacement (flatten and fusion) of foot processes, but glomeruli is NL.
74
Q

Minimal Change Disease is most offten seen in who?

What condition is it often a cause of?

A
  • Children 2-6
  • Hodgkins Lymphoma and lymphoreticular disorders, which release MASSIVE amounts of cytokines.
75
Q

What is main presenting sign in MCD?

What sx RARELY develops?

A
  1. Edema
  2. Rarely develop HTN
76
Q

Minimal change disease often has a __________, which causes the release of cytokines.

A

Immunological trigger

  1. Viral infection (URI)
  2. Allergic reaction
  3. Recent immunization
77
Q

How do we treat MCD?

A
  • Corticosteroids and immunosuppressants – very responsive (90% of children)
78
Q

What are 5 features of minimal-change disease which point to an immunologic basis for its development?

Increased incidence in pts with what conditions and cancer?

A
  1. Occur after: URI and immunizations
  2. Responds to corticosteroids

3. Assoc. w/ atopic disorders (i.e., eczema, rhinitis)

  1. Increased prevalence of certain HLA haplotypes
  2. Increased incidence in pts w/ Hodgkin lymphoma
79
Q

What is the SEVERE version of minimal change disease?

A

Focal Segmental Glomerulosclerosis (FSGS)***

80
Q

What is the most common cause of nephrotic syndrome in adults U.S. AND WESTERN SOCIETY (35%)?

A

_Focal Segmental Glomerulosclerosis (FSGS)***_

81
Q

FSGS is usually primary/secondary, but there are many ______ causes.

Often, it is a adaptive response to what?

A

FSGS is usually primary (idiopathic) but there are many secondary causes.

Often, a response to a loss of renal mass

82
Q

What are the secondary causes of FSGS?

A
  • 1. HIV (collapsing variant of FSGS):
    • African Americans > Caucasians
  • 2. SS (Sickle Cell)
  • 3. Heroin
  • 4. Massive obesity
83
Q

What is FSGS and how does it occur?

A
  1. Unknown causes (idiopathic) damage podocyte => proteinuria.
  2. Overtime, proteins and lipids get trapped & build-up in the glomerulus => resulting in hyalinosis => sclerosis
  3. Sclerosis => collapse of the BM in a segment of some glomeruli (focal) in the kidney
84
Q

Where does the damasge occur in FSGS?

A

Segments of SOME glomeruli, not all are affected.

85
Q

FSGS

  1. LM
  2. EM
  3. Immunoflourescence
A
  1. LM: Hylanosis and sclerosis of a segment of a glomeruli in SOME glomeruli
  2. EM: Effacement of foot processes; sclerosis
  3. Immunoflourescence: sometimes focal deposits of IgM and compliment
86
Q

What is the ONLY way to dx FSGS?

A

BIOPSY

87
Q

Which populations have a higher incidence of primary Focal Segmental Glomerulosclerosis (FSGS)?

A

1. African Americans

2. Hispanics

88
Q

The clinical signs of FSGS differ from Minimal Change disease in what 4 ways?

A
  1. Higher incidence of hematuria, reduced GFR and HTN
  2. Proteinuria is often nonselective
  3. Doesn’t respond well to steroids
  4. Poor prognosis: can progress to CKD ==> 50% developing ESRD within 10 years
89
Q

What is the most characteristic lesion (i.e, morphological variant of FSGS) seen in HIV-associated nephropathy, a type of FSGS.

A

Collapsing glomerulopathy = severe form of FSGS

90
Q

What is the prognosis of FSGS in children vs. adults?

A
  • Children generally have better prognosis than adults
91
Q

FSGS is nephritic/nephrotic?

A

Can be considered MIXED; nephrotic sydrome w nephritic characteristics

92
Q

The collapsing variant of FSGS in HIV patients is most common in what population?

A

African American

93
Q

Is Membranoproliferative Glomerulonephritis (MPGN) a disease?

A

No, it is a type of injury d/t immunity.

94
Q
  • Membranoproliferative glomerulonephritis (MPGN) is a group of rare glomerular disorders that can cause _________ syndrome. What occurs?
A

Nephritic or nephrotic syndrome

  1. Infiltration of acute inflamm cells (neutrophils)
  2. Thickening of BM
  3. Hypercellularity: mainly mesangial, but can also be capillary
    • Capillary loops
      mesangial: mesangial interposition occurs, where mesangial cells proliferate & ​extend into the thickened BM => splits BM (producing “double countour”), forming a “tram track appearance” on LM
    • Increases mesangial matrix
95
Q

MPGN causes varying degrees of renal dysfunction, such as:

A
  • 1. Renal failure (high BUN and creatinine)
  • 2. Proteinuria
  • 3. Hematuria
  • 4. Thick BM, hyperceullarity
96
Q

In MPGN, how will the architecture of the lobules change?

A

They will become more accentuated.

97
Q

Membranoproliferative Glomerulonephritis (MPGN) is also called ___________ glomerulonephritis.

A

Mesangiocapillary

98
Q

What is the difference in the pathology of MPGN Type 1 and MPGN Type 2?

A
  • MPGN Type 1: subendothelial immune complexes deposits that contain IgG and compliment
  • MPGN Type 2: electron dense deposits of C3 (compliment) in the BM, not subendothelium
99
Q

What are the differences between Type 1 and Type 2 Membranoproliferative Glomerulonephritis?

A
  • Only difference (in terms of pathology) is where deposits are:
    • MPGN Type 1 (most common): Deposition of IgG/compliment immune complexes in the subendothelium
      • ​tram-track appearance
    • MPGN Type 2 (Dense Deposit Disease): deposition of C3a/C3b deposits in the BM (not subendothelium) and decreases levels of C3
100
Q

What causes the C3 deposits in the BM in MPGN Type 2 (dense deposit disease)?

A
  1. C3 nephritic factor (C3NeF, an IgG autoAb)) inapprop activates the alternative compliment pathway
    1. Binds to C3 convertase => stabilizes => prolong activation => increase C3a and C3b
    2. => deposit in BM
    3. => inflammation in BM and low levels of C3
101
Q

Which causes tram track appearance MPGN Type 1 or Type 2?

A

Both

102
Q

When do most cases of primary MPGN Type I present?

How do they present?

A
  • MC in children or young adults mostly, but can affect all ages
  • Nephrotic syndrome & nephritic component manifested by:
  • Proteinuria, microscopic hematuria, HTN (~30), oliguria, some edema, and renal insufficiency
103
Q

About 50% of patients with MPGN Type I will develop what?

Response to immunosuppressant therapy?

A
  • Chronic renal failure in 10 years
  • Not proven to be beneficial
104
Q

Who does secondary MPGN Type I present in?

Arises in which settings and with what associated disorders?

A
  • Almost exclusively in adults
  • Arises d/t chronic antigenemia (from infection, autoimmune dz or neoplasia), which causes immune complex deposition
    • SLE, HBV, HCV (w/ cryoglobulinemia), endocarditis, HIV, and schistosomiasis
  2. - α1- antitrypsin deficiency
    • Malignancies (CLL, lymphomas, melanomas)
105
Q

Most patients w/ dense deposit disease (aka type II MPGN) have abnormalities reulting in excessive activation of?

A

Alternative complement pathway

106
Q

Dense deposit dz (MPGN type II) primarily affects whom?

Only occurs as what kind of disease?

A
  • Children
  • Only occurs as a primary renal disease; no secondary form
107
Q

What is the dominant clinical finding in Dense Deposit disease vs. MPGN type I?

Prognosis of MPGN II vs. MPGN I?

A
  • MPGN type 1: proteinuria
  • MPGN type 2: hematuria
    • 50% of patients will also have nephritic syndrome and 50% will get ESRD in 10 years
    • Poorer prognosis than MGPN I due to most pts having severe renal dz.
108
Q

High incidence of recurrence of MPGN II in which patients?

A

Transplant patients, indicating importance of a circulating factor

109
Q

In MPGN 1 & 2, on LM we see (hypercellularity, GBM splitting, leukocyte infiltration and tram-track appearance)

What do we see on EM and IF for each?

A

Type 1

  • EM: subendothelial deposits of immune complexes
  • IF: IgG, C3; C1q and C4

Type 2

  • EM: electron dense deposits in BM that look like ribons (seen in pic)
  • IF: C3 and properidin (no IgG, C1q or C4)
    *
110
Q

What is the most common type of glomerulonephritis worldwide?

What about in the US?

A
  • IgA nephropathy: worldwide
  • FSGS: USA
111
Q

What is IgA nephropathy (Berger Disease)?

A
  • a overactive immune system that causes an ↑ IgA production, forming of IgA-IgG immune complexes in response to triggers such as:
    • Respiratory infection
    • GI infection
112
Q

IgA nephropathy is an overactive immune system that produces excessive IgA, due to what?

A

Viral (MC) infections

  • Respiratory infection
  • GI infection
113
Q

IgA-IgG immune complexes cause pathology and inflammation where?

A

Where they deposit (mesangium)

114
Q

IgA-IgG immune complexes form in the mesangium. What happens next?

A
  1. => Light + of compliment pathway via alternative and lectin pathway (no hypocomplementemia)
  2. => Inflammation due to release pro-inflammatory cytokines and MO => damage of glomerulus
115
Q

Will a person with IgA nephropathy develop hypocomplantemia? Why

A

No because compliment is LIGHLTY activated

116
Q

IgA nephropathy is primarily a disease seen in whom?

Which ethnicities more affected?

Which sex?

A
  • Older children and young adults (20s-30s)
  • White ppl and Asians > African Americans
  • Male predominance: 2:1 or higher (N. America and Europe)
117
Q

What are the MAIN pattern of of IgA nephropathy (Berger disease)?

A

IgA1-IgG immune complex deposition in mesangium (GLOBAL) with only recurrent microscropic/gross hematuria for a long time (20 years), before developing into chronic renal failure.

118
Q

IgA Nephropathy (Berger Disease)

  • LM
  • EM
  • IF
A
  • LM: Focal proliferation and widening of the mesangium
  • EM: Mesangial and paramasangial dense deposits
  • IF: Granular IgA-IgG immune complexes, IgM and C3 in the mesangium
    • ​No C1q or C4 bc altenrative path was +
119
Q

Due to increased synthesis of abnormal IgA, there is an increased incidence of IgA nephropathy seen in which 2 conditions?

A
  1. Celiac disease (gluten enteropahty)
  2. Liver disease (defective hepatobiliary clearance of IgA) –> secondary IgA nephropathy
120
Q

Pts with IgA nephropathy commonly present with hematuria following what?

How long does it last?

A
  • Respiratory infection or, less commonly the GI/GU tracts
  • Hematuria lasts several days, then subsides, only to return every few months since childhood
121
Q

What clinical outcome occurs in a majority of patients with IgA nephropathy?

A
  • Recurrent episodes of hematuria w/o progression of renal disease
122
Q

What are the clinical outcomes of IgA nephropathy progressing to a renal disease?

A
  • 5-10% of patients will progress to acute nephritic syndrome w/ HTN
  • 15-40% will progress to chronic renal failure over 20 year period
123
Q
  • Post-strep GN: occurs _____ after infection
  • Minimal change: occurs:
  • IgA Nephropathy: occurs:
A
  • weeks
  • nephrotic syndrome after URI
  • recurrent episodes of gross/microscopic hematuria since childhood, URI, diarrhea
124
Q

IgA nephropathy without extra renal involvement is called __________.

What about if there is extra-renal involvement?

A
  1. Berger Disease
  2. Henoch-Scholein Purpra (HSP
125
Q

What is Henoch-Schonlein purpura (HSP)?

Typical clinical presentation?

A
  • IgA nephropathy associated w/ systemic disease –> onset following URI
  • Presents w/ cramping & pain + hematuria and proteinuria
126
Q

What is an isolated glomerular abnormality?

A

IgA Nephropathy, because patient can be asymx for a LONG TIME

127
Q

If a pt presents with glomerulonephritis syndrome with hypocomplimentemia, what is the most common dx?

A
  1. Membranoproliferative GN Type 2
128
Q

MPGN Type 1 and 2: which is more a nepritic/nephrotic syndrome

A
  • Type 1: nephrotic syndrome w nephritic findings
  • Type 2: nephritic
129
Q

Is Chronic Glomerulonephritis a diagnosis?

A

Yes

130
Q

Chronic Glomerulonephritis causes what?

A
  • Chronic renal failure/ chronic kidney disease
131
Q

What stain is used to view Chronic Glomerulonephritis and what is seen?

A

_Trichome stain (_stains blue) shows obliteration and replacement of all glomeruli with acellular eosinophillic masses.

132
Q

Do we always know what causes chronic glomerulonephritis?

A

NO. Many cases arise mysteriosly due to the end-result of relatively asymptomatic forms of glomerulonephritis that progress to uremia.

133
Q

What PRIMARY glomerular disease most commonly become chronic glomerulonephritis (CGN)?

A
  1. 90% of Cresenteric GN
  2. 50-80% of FSGS
  3. 50% of membranoproliferative
  4. 30-50% of IgAN and membranous nephropathy
  5. 1-2% of post-strep GN
134
Q

What are the 2 hereditary nephritis?

A
  1. Alport syndrome
  2. Thin Basement Membrane Disease (Benign Familial Hematuria)
135
Q

80% of patients with a family history of hematuria or recurrent hematuria during childhood have either

A
  1. Alport
  2. Thin Basement Membrane Disease (more likely).
136
Q

Alport & Thin Basement Membrane Disease are both isolated glomerular abnormalities and associated with mutations in in what gene?

Where in the kidney do we see the problem?

A
  • Collagen gene that effect collagen
  • Reflected by abnormalities of the BM.
137
Q

What is Alport syndrome?

A
  • A multi-system disease that produces a nephritic syndrome: hematuria that progresses into chronic renal failure.
138
Q

What symptoms are associated with Alport?

A
  • Triad (cant pee, cant see, cant hear a bee)
    • 1. Hematuria that progresses into chronic renal failure.
      1. Hearing loss
      1. Eye disturbance
139
Q

What is the major inheritance pattern of Alport Syndrome?

How does this effect the presentation in men and women?

A

X-linked (more common in Males)

140
Q

Alport Disease is due to mutations in genes encoding subunits of which molecule?

A

COL4A5 (type 4 collagen, alpha5 chain)

141
Q

Alport Syndrome

  • LM
  • EM:
  • Immunohistochemistry:
A
  • LM: NL (until late in the disease)
  • EM: Basket weave appearance
    • Irregular thickening of BM with alternating attenuation (thinning)
    • Splitting/lamination of the lamina densa, and foci of rarefaction
  • IF: absence of a3, a4, and a5 staining
142
Q

Symptoms of Alport Syndrome typically manifest btw what ages?

Frequent presentation?

A

- 5-20 yo w/ onset of overt renal failure btw ages 20-50

  • Present w/ hematuria with red cell casts
143
Q

What is Thin Basement Membrane Disease?

A

Hereditary disorder that causes asymptomatic microscopic hematuria due to a thin BM (150-250 nm, compared to 300-400 nm) and rarely leads end-stage disease

144
Q

What is renal function like and the prognosis for TBM Disease?

A

NL kidney function and excellent prognosis

145
Q

Which is more likely to lead to chronic renal failure/ESRD: Alport or TBMD?

A
  • Alport.
  • TBMD rarely leads to ESRD.
146
Q

The thin BM’s in Thinned BM Disease is due to mutations in genes encoding what?

Most patients are what type of carriers?

A
  • Type IV Collagen – a3 or a4 chain gene mutations
  • Heterozygous carriers
147
Q

Homozygotes with Thinned BM Disease resemble what other hereditary nephritis?

A

AR Alport

148
Q

Which stain is used to view Chronic Glomerulonephritis?

What’s seen?

A
  • Trichrome stain
  • Shows:
    • replacement of almost all glomeruli w collagen
    • obliteration of glomeruli with acellular masses of eosinophils
      *
149
Q

As glomeruli progressively become obliterated in chronic GN, what happens to GFR and protein loss?

A

- GFR decreases

  • Protein loss in urine diminshes
150
Q
A

CPR Exam 2 (29 decks)

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