Pathology 1, 2, 3 Flashcards
(119 cards)
1
Q
What is azotemia?
A
Elevation of the blood urea nitrogen (BUN) and creatinine levels
Decreased glomerular filtration rate
2
Q
What is prerenal azotemia?
A
Hypoperfusion of the kidneys–> Impairs renal function in the absence of parenchymal damage
3
Q
What can cause prerenal azotemia?
A
Hemorrhage, shock, volume depletion, and CHF
4
Q
This is when urine flow is obstructed beyond the level of the kidney.
A
Postrenal azotemia
5
Q
What is it when you have azotemia associated with a constellation of clinical signs, symptoms, and biochemical abnormalities
A
Uremia
6
Q
Describe diminished renal reserve.
A
GFR 50% notmal
BUN creatinine normal
Patient asymptomatic
7
Q
What is seen in renal insufficiency?
A
GFR 20-50% normal
Azotemia (anemia and HTN)
Polyuria and nocturia (decreased concentrating ability)
8
Q
What is the GFR in chronic renal failure
A
Less than 20-25% normal
Kidneys cant regulate volume and solute concentration
9
Q
What symptoms are seen with chronic renal failure?
A
Edema, metabolic acidosis, and hyperkalemia
10
Q
What is it called when the GFR is less than 5% normal and the patient is in the terminal stage of uremia?
A
End-stage renal disease
11
Q
Nephritic?
A
- Hematuria (RBC casts)
- HTN
- Azotemia
- Oliguria
- Proteinuria (under 3.5g/day)
12
Q
Nephrotic?
A
- Severe proteinuria (more than 3.5/day)
- Hypoalbuminemia (less than 3g/dL)
- Generalized edema
- Hyperlipidemia
- Lipiduria
13
Q
4 types of histologic alterations?
A
- Hypercellularity
- BM Thickening
- Hyalinosis
- Sclerosis
14
Q
What diseases is hypercellularity associated with?
A
Inflammatory diseases
15
Q
What are the cellular changes seen in hypercellularity?
A
- Cellular proliferation (increased cellularity) in the mesagnial or endothelial cells
- Leukocytic infilatration (neutrophils, monocytes, lymphocytes)
- Crescent formation
16
Q
What’s a crescent?
A
Acuumulation of cells composed of proliferating parietal epithelial cells and infiltrating leukocytes
(dark proliferation of cells)
17
Q
Do the proximal convoluted tubules have a lot of cytoplasm?
A
YES
Remember, the DCT aren’t as big and puffy as the PCT
18
Q
What do you see in light mycroscopy for basement membrane thickening?
A
Thickening of the capillary walls
19
Q
What is seen deposited on EM for basement membrane thickening?
A
Amorphous electron-dense material (usually immune complexes)
20
Q
Where are the amorphous electron-dense material (immune complexes) seen in EM for basement membran thickening seen?
A
Endothelial or epithelial side of the BM or withing the GBM itself
21
Q
What else can be seen in EM for basement membreane thickening
A
Thickening of the basement membrane (due to increased synthesis of protein components (glomerulosclerosis)
22
Q
What is seen on light microscopy and electron microscope in hyalinosis
A
Light: Accumulation of homogenous, eoinsophilic material
Electron: Extracellular and amorphous material
23
Q
What hyalinosis composed of?
A
Plasma proteins insudated from circulation into glomerular structures
24
Q
What can hyalinosis cause?
A
Extensive change…it can obliterate capillary lumens of the glomerular tuft
25
What is hyalinosis a consequence of and where is it commonly seen?
Consequence of glomerular damage and is common seen in focal segmental glomerulosclerosis (also diabetes)
26
What is sclerosis?
Accumulations of extracellular collagenous matrix confined to the mesangium (diabetic glomerulosclerosis)/involving capillary loops
27
What happens to the capillary lumens in sclerosis?
They are obliterated (some or all) in affected glomeruli
28
What is formed in capillary lumens in affected glomeruli in sclerosis?
Formation of fibrous adhesions
| -Sclerotic portions of glomerulus and parietal epithelium of Bowman's capsule
29
What is seen in acute proliferative (poststreptococcal/postinfectious) glomerulonephritis?
Diffuse proliferation of glomerular cells and influx of leukocytes
30
What is the cause of acute proliferative glomerulonephritis?
Immune complexes depositing
31
When can you see acute proliferative glomerulonephritis?
1-4 weeks after streptococcal infection (pharynx or skin)
32
What ages do you see acute proliferative glomerulonephritis in?
6-10
| -Adults can be affected too
33
What is seen on light microscopy for acute proliferative glomerulonephritis?
- Enlarged, hypercellular glomeruli (infiltration by leukocytes, proliferation of endothelial and mesangial cells, and crescent formation)
- Interstitial edema and inflammation
- Tubules have red cell casts
34
What is seen on IF for acute proliferative glomerulonephritis?
Granular deposits of IgG, IgM, and C3 in the mesangium and along the GBM
35
What is seen on EM for acute proliferative glomerulonephritis?
Discrete, amorphous, electon-dense deposits on the epithelial side of the membrane (subepithelial) --> HUMPS
36
What is the clinical presentation for acute proliferative glomerulonephritis?
- Young child
- Abrupt development of malaise, fever, nausea, oliguria, and hematuria
- 1-2 weeks after recovery from a sore throat
- Red cell casts in the urine
- Mild proteinuria (usually less than 1gm/day
- Periorbital edema
- Mild-moderate HTN
37
What lab findings are seen with acute proliferative glomerulonephritis?
- Elevations of antistreptococcal antibody titers
| - Decline in serum concentrations of C3
38
3 central features of rapidly progressive glomerulonephritis (crescentic glomerulonephritis)?
1. Severe glomerular injury
2. Rapid and progressive loss of renal function
3. Severe oliguria and signs of nephritic syndrome
39
What is the most common histologic picture of rapidly progressive glomerulonephritis?
Presence of crescents
- Proliferation of parietal epithelial cells lining Bowman's capsule
- Infiltration of monocytes and macrophages
40
Does rapidly progressive glomerulonephritis cause death?
YES... death from renal failure occurs in weeks to months if untreated
41
What are the 3 groups of rapidly progressive glomerulonephritis?
- Anti-GBM antibody induced disease (Goodpasture Syndrome)
- Immune complex deposition
- Pauci-immune type
42
What is seen in anti-GBM antibody-induced disease (Goodpasture syndrome)?
Linear deposits of IgG and C3 in the GBM
43
How is anti-GBM antibody-induced diseases (Goodpasture syndrome) treated?
Plasmapheresis
44
When do you see immune complex deposition associated with crescentic glomerulonephritis?
Post-infections, LN, IgA nephropathy, HSP
45
What kind of staining is seen with immune complex deposition associated with crescentic glomerulonephritis?
Granular pattern
46
What do you do to treat immune complex deposition associated with crescentic glomerulonephritis?
Treat underlying disease
47
What 2 things are characteristic of pauci-immune type rapidly progressive glomerulonephritis?
1. Lack of anti-GMB antibodies or immune complexes by IF and EM
2. Circulating antineutrophil cytoplasmic antibodies (ANCAs)
48
What is seen on gross examination for rapidly progressive glomerulonephritis?
- Big, pale kidneys
| - Petechial hemorrhages on the cortical surfaces (flea-bitten kidneys)
49
What are 5 things seen on light microscopy in rapidly progressive glomerulonephritis?
1. Distinctive crescents (proliferation of parietal cells and by migration of monocytes and macrophages into the urinary space...+/- neutrophils and lymphocytes)
2. Fibrin strands: Between the cellular layers of the crescents
3. Possible focal necrosis of glomeruli
4. Focal or diffuse endothelial proliferation
5. Mesangial proliferation
50
What is seen on IF in anti-GBM antibody-induced disease?
Linear GBM fluorescence for Ig and complement
51
What is seen on IF in immune complex-mediated cases of rapidly progressive glomerulonephritis?
Granular immune depsorts
52
What is seen on IF in pauci-immune cases of rapidly progressive glomerulonephritis?
Litte or no deposition of immune reactants
53
What is seen on EM in rapidly progressive glomerulonephritis?
Deposits (in immune complex cases) and distinct ruptures in the GBM
54
What are the clinical symptoms in rapidly progressive glomerulonephritis?
- Hematuria with RBC casts in urine
- Moderate proteinuria: Can reach nephrotic range
- Variable HTN and edema
- With disease progression: Severe oliguria
55
What is see in the serum analysis with rapidly progressive glomerulonephritis?
Depends on which type it is:
1. Anti-GBM antibody-induced disease: Anti-GBM antibodies
2. Immune complex-mediate disease: Antinuclear antibodies
3. Pauci-immune cases: Antineutrophil cytoplasmic antibodies
56
What is the most common cause of nephrotic syndrome in adults?
Membranous nephropathy
57
What is seen in membranous nephropathy?
Diffuse thickening of the glomerular capillary wall
58
What causes the glomerular capillary wall thickening in membranous nephropathy?
Accumulation of electron-dense, Ig containing deposits along the SUPEPITHELIAL side of the BM
59
What are the associations with memranous nephropathy?
1. Malignant tumors (lung, colon, melanoma)
2. SLE
3. Infections (Hep B/C, syphillis, schistosomiasis, malaria)
4. Other autoimmune disorders (thyroiditis)
60
What is found on light microscopy for membranous glomerulonephropathy?
The glomeruli are normal in the early stages of the disease, but they can exhibit uniform, diffuse thickening of the glomerular capillar wall and SPIKES
61
What is see on EM for membranous nephropathy?
Irregular dense deposits of immune complexes between the BM and overlying epithelial cells (subepithelial)
62
What is seen on IF for membranous glomerulonephropathy?
Granular deposits of immunoglobulins and complement
63
Clinical features of membranous nephropathy?
1. Insidious onset of the nephrotic syndrome
2. Hematuria
3. Mild HTN present in 15% -35% of cases
64
What is a predictor of poor prognosis in membranous nephropathy?
Concurrent sclerosis of the glomeruli
65
What 2 conditions are spontaneous remissions/benign outcome more common in for membranous nephropathy?
1. Women
| 2. Porteinuria in the non-nephrotic range
66
What is the most frequent cause of nephrotic syndrome in children?
Minimal change disease
67
What is the age group you will see minimal change disease in?
2-6
68
When do you commonly see minimal change disease develop?
Following a respiratory tract infection or routine prophylactic immunization
69
What can be given to treat minimal change disease?
Corticosteroids
70
What is seen on light microscopy in minimal change disease?
Normal glomeruli
71
What is seen on EM for minimal change disease?
Diffuse effacement of foot processes of visceral epithelial cells (podocytes) in the glomeruli
72
What are the clinical features associated with minimal change disease?
1. Massive proteinuria
2. Good renal function (no azotemia)
3. No HTN or hematuria
73
If an adult has minimal change disease, what is the most common association with it?
Hodgkin lymphoma
74
What are 2 big characteristics of focal segmental glomerulosclerosis?
1. Sclerosis of some, but no all glomeruli (in affected glomeruli, a portion of the capillary tuft is involved (segmental)
2. Nephrotic syndrome or heavy proteinuria
75
What are the 5 types of focal segmental glomerulosclerosis?
1. Primary disease (idiopathic)
2. Association with other conditions (*HIV infection, heroin addiction, *sickle-cell disease, obesity)
3. Secondary event (IgA nephropathy)
4. Component of the adaptive response to loss of renal tissue in advanced stages of other renal disorders
5. Inherited (uncommon)
76
In focal segmental glomerulosclerosis are the lesions seen on light microscopy involving all of the glomeruli?
NO
-The focal and segmental lesions may involve only a minority of the glomeruli... you can miss this is the biopsy doesn't have enough glomeruli in it
77
What is seem on light microscopy for focal segmental glomerulosclerosis?
1. Lipid droplets and foam cells
| 2. Pronounced hyalinosis and thickening of afferent arterioles
78
What is collapsing glomerulopathy?
Retraction and/or collapse of the entire glomerular tuft seen in focal segmental glomerulosclerosis
79
What patient population do you normall see collapsing glomerulopathy in?
HIV-associated nephropathy
80
What 2 things are seen on EM for focal segmental glomerulosclerosis?
1. Diffuse effacement of foot processes
| 2. Focal detachment of the epithelial cells and denudation of the underlying GBM
81
What is seem IF for focal segmental glomerulosclerosis?
IgM and C3 (seen in scleotic areas or mesangium
82
What are 3 general characteristics of membranoproliferative glomerulonephritis?
1. Alterations in the glomerular BM
2. Proliferation of glomerular cells
3. Leukocyte infiltration
83
Is membranoproliferative glomerulonephrotis nephrotic or nephritic?
BOTH...it's a combined picture
84
What are the 2 types of membraoproliferative glomerulonephritis?
Primary: Idiopathic (split into type 1 and type 2
Secondary: Systemic disorders/known etiologic agents
85
What is used to differentiate type 1 and type 2 primary membranoproliferative glomerulonephritis?
EM and IF (looks same on light microscopy)
86
What is seen in light microscopy for membranoproliferative glomerulonephritis?
- Glomeruli are large and hypercellular
- Proliferation of cells in the mesangium
- Endocapillary proliferation involving capillary endothelium and infiltrating leukocytes
- Crescents/Lobular appearance
- Glomerular capillary wall looks double-contour or TRAIN-TRACK
87
Which is more common...type 1 or type 2 primary membranoproliferative glomerulonephritis?
Type 1
88
What is seen in Type 1 MPGN in EM, IM?
EM: Discrete subendothelial electron-dense deposits and mesangial and occasional subepithelial deposits
IM: C3 deposited in granular pattern, IgG and C1q/C4
89
What is seen in Type 2 MPGN in EM, IM?
EM: Lamina densa of the GBM transformed into an irregular, ribbon-like, extremely electron-dense structure
IM: C3 in irregular granular or linear foci in BM on either side (not within the dense deposites, C3 present in the mesangium in characteristic circular aggregates (mesagnial rings)
90
What is usually absent in IF for Type 2 MPGN that is a pertinant negative?
IgG, C1q, and C4
91
What is the most common type of glomerulonephritis worldwide?
IgA Nephropathy
92
What is characteristic for IgA Nephropathy?
Presence of prominent IgA deposits in the mesangial regions
93
What does IgA nephropathy frequently cause?
Recurrent gross or microscopic hematuria
94
What other 2 clinical findings are seen with IgA nephropathy?
1. Mild proteinuria
| 2. Nephrotic syndrome- occasionally
95
What is seen on light microscopy for IgA nephropathy?
Glomeruli may be normal, have mesangial widening and endocapillary proliferation, or leukocytes within glomerular capillaries
96
What is seen on EM for IgA nephropathy?
Presence of electron-dense deposits in the mesangium
97
What is seen on IF for IgA nephropathy?
Mesangial deposition of IgA and C3 and properdin and lesser amounts of IgG or IgM
98
What are the 4 clinical characteristics of Henoch-Schonlein Purpura?
1. Purpuric skin lesions: Extensor surfaces of arms/legs and buttocks
2. Abdominal: Pain, vomiting, GI bleeding
3. Nonmigratory arthralgia
4. Renal Abnormalities: Hematuria, Nephritic or nephrotic syndrome
99
What age groups does Henoch-Schonlein Purpura affect?
3-8 (but it can occur in adults)
100
When is Henoch-Schonlein Purpura seen
Onset often follows an URI
101
What are 3 main characteristics seen on morphology for Henoch-Schonlein Purpura?
1. Mild focal mesangial proliferation
2. Diffuse mesangial proliferation
3. Crescentic glomerulonephritis
102
What is seen on IF for Henoch-Schonlein Purpura?
Deposition of IgA (somtimes IgG and C3) in the mesangial region
103
What are the skin lesions seen in Henoch-Schonlein Purpura and what do they contain?
- Subepidermal hemorrhages
- Necrotizing vasculitis of the small vessels in the dermis
- Contain IgA deposits
104
What 3 conditions discussed affect children and what are there age ranges?
- Post-Streptococcal Glomerulonephritis: 6-10
- Minimal Change Disease: 2-6
- Henoch-Schonlein Purpura: 3-8
105
Which 2 diseases that affect children mostly occur after a URI and how could distinguish between these 2?
- Minimal change disease and Henoch-Schonlein Purpura
| - Distinguish because Henoch-Schonlein Purpura will have the skin lesion
106
What is Alport Syndrome?
Hereditary nephritis- Group of hetergenous familial renal diseases associated primarily with glomerular injury
107
What clinical features are associated with Alport syndrome?
- Hematuria with progression to chronic renal failure
- Nerve deafness
- Various eye disorders (lens disolcation, posterior cataracts, corneal dystrophy)
108
How is Alport syndrome most commonly inherited?
85% of cases are X-linked
109
In Alport syndrome inherited X-linked do males express the full syndrome, do females?
- Males express the full syndrome
| - Females are carriers and may only experience mild hematuria
110
If Alport syndrome is inherited AR or AD, are males and females equally susceptible to developing the full syndrome?
YES
111
What do the glomeruli look like morphologically in Alport Syndrome?
- Diffuse GBM thinning
- GBM show irregular foci of thickening alternating with attenuation (thinning)
- Splitting and lamination of the lamina densa (BASKET-WEAVE)
112
What is seen in the interstitium in Alport Syndrome?
Foam cells filled with neutral fats and mucopolysaccharides
113
What can Alport Syndrome progress to?
Focal segmental and global glomerulosclerosis
114
What is the most common presenting sign seen in Alport Syndrome?
- Gross or microscopic hematuria
| - Red cell casts
115
When do symptoms develop in Alport Syndrome?
5-20
116
WHen does the onset of overt renal failure occur in Alport Syndrome?
20-50 in men
117
What is chronic glomerulonephritis?
End-stage glomerular disease
118
What conditions can lead to chronic glomerulonephritis?
1. Poststreptococcal glomerulonephritis
2. Crescentic glomerulonephritis
3. Membranous nephropathy
4. MPGN
5. IgA Nephropathy
6. FSGS
119
What are the 7 morphological features seen in chronic glomerulonephritis?
1. Symmetrical contraction of the kidneys (diffusely granular cortical surfaces)
2. Cortex is thinned with an increase in peripelvic fat
3. Obliteration of glomeruli (acellular eosinophilic masses)
4. Arterial and arteriolar sclerosis
5. Marked atrophy of associated tubules
6. Irregular intersitial fibrosis
7. Mononuclear leukocytic infiltration of the interstitium
2.
