Structural Renal Pathology Flashcards
1
Q
Name 4 general types of Glomerular Disease
A
- Podocyte
- Immune Complex
- GBM Disease
- Vascular Injury
2
Q
Name 2 specific podocyte glomerular diseases
A
- Minimal change disease
2. Focal Segmental Glomerulosclerosis
3
Q
Name 4 specific Immune Complex glomerular diseases
A
- APSGN (subepithelia)
- Membranous Nephropathy (subepithelia)
- MPGN (subendothelial)
- IgA Nephropathy (Mesangial)
4
Q
Name 4 specific GBM diseases
A
- Anti-GBM Disease
- Goodpastures
- Alport’s Syndrome
- Thin Basement Membrane
5
Q
Name 6 specific Vascular Injury glomerular diseases
A
- ANCA-associated glomerulonephritis
- Pauci-Immune glomerulonephritis
- Hemolytic Uremic Syndrome/TTP (TMA)
- Wegener’s Granulomatous
- SLE
- Scleroderma/Systemic Sclerosis
6
Q
What is the etiology of Focal Segmental Glomerulosclerosis?
A
Primary: Idiopathic
Secondary: Reduced nephron mass
7
Q
What are some of the causes of reduced nephron mass in Focal Segmental Glomerulosclerosis?
A
- Familial Sporadic Mutations
- HIV, Parvovirus
- Heroin, lithium, IFN-alpha
- Chronic kidney disease
- suPAR
8
Q
What is the mechanism of the suPAR subtype of FSGS?
A
suPAR - circulating factor from WBCs that activate B3 integrin (anchor for podocytes to GBM), high activity of B3 integrin»_space; podocyte dysfunction
9
Q
Name and describe the 5 sub-types of Focal Segmental Glomerulosclerosis
A
- Collapsing
- Cellular
- Tip
- Perihilar
- Not otherwise specified
10
Q
Which subtypes of FSGS presents with heavy proteinuria?
A
Collapsing & Tip
11
Q
Which subtype of FSGS has the best prognosis?
A
Tip: more likely to achieve remission
12
Q
Which FSGS has the worst prognosis and what causes it?
A
Collapsing: heavy proteinuria, worst renal survival
—- HIV (glomerular tuft collapse)
13
Q
What Familial Sporadic Mutations cause Focal Segmental Glomerulosclerosis?
A
Mutations in:
- podocin
- nephrin
- alpha-actinin-4
- transient receptor channel 6
14
Q
What is the clinical presentation of Focal Segmental Glomerulosclerosis?
A
- Nephrotic syndrome (second most common in adults)
- Non-specific loss of proteins (albumin AND globins)
- HIV patient (FSGS is most common cause of glomerular disease in HIV patients)
15
Q
What are the Light Microscopy characteristics of FSGS?
A
- scarring
- Obliterated capillary lumen (hyalinosis)
- Areas of adhesion to Bowman’s capsule
- Expansion of mesangial matrix
16
Q
What is the immunohistochemistry of FSGS?
A
Normal; easy to confuse w/ MCD
+/- non-specific Ig+
17
Q
What is the EM of FSGS?
A
Effacement / fusion of foot processes
18
Q
How do you treat FSGS?
A
- Corticosteroids (less likely to remit)
- Calcinuerin inhibitors
- Mycophenolate Mofetil
- Sirolimus
19
Q
What is the etiology of Acute Post-infections Glomerulonephritis
A
Post-immune response to nephritogenic Group A streptococcal strains
20
Q
Which bacteria, viruses and parasites cause Acute Post-infections Glomerulonephritis?
A
Bacterial: Group A beta-hemolytic streptococci - nephritogenic
Virus: HBV, EBV, mumps
Parasites: malaria, toxoplasmosis
21
Q
Acute Post-Infections Glomerulonephritis follows the “Filtered Cationic Antigen” theory. Explain this theory.
A
cation filters through endothelial but charge restricted sub-podocyte. Antibodies localize and target.
22
Q
What is the clinical presentation of Acute Post-infections Glomerulonephritis?
A
- Nephritic
- Gross hematuria (tea/cola colored)
- 1-3 weeks after URI
- throat, skin, strep infections
- school children
- edema
- hypertension
- pulm/GI symptoms
- Ascites 2:1 males to females
23
Q
Light microscopy of Acute Post-infections Glomerulonephritis?
A
- Proliferation
- Inflammation = membranoproliferative disease
24
Q
Immunohistochemistry of Acute Post-infections Glomerulonephritis?
A
C3+
IgG+
25
EM of Acute Post-infections Glomerulonephritis?
Subepithelial Humps (immune complexes)
26
Lab profile of Acute Post-infections Glomerulonephritis?
- Hypocomplementemia (low C3, but normal C4 = alternate pathway activation)
- Low cryoglobulinemia
- Anti-streptolysin O titers elevated (throat)
- Anti-DNAase/hyaluronidase titers elevated (skin)
27
What is the treatment of Acute Post-infections Glomerulonephritis?
- Treat underlying infection
- Hypertension: loop diuretics
- Renal replacement therapy if severe dysfunction
- may resolve spontaneously
28
What is Membraneous Nephropathy?
Autoimmune disease w/ Ab directed at podocyte protein
29
What is the Primary/Idiopathic etiology of Membranous Nephropathy?
In-situ immune complex formation
30
What is the Primary/Idiopathic pathogenesis of Membranous Nephropathy?
In-situ immune complex formation
- podocyte damage from MAC (complement)
- Autoantibody to M Type Phospholipase A2 receptor (PLA2R)
- --- receptor expressed by podocytes in normal glomeruli
- --- colocalizes with IgG4
- locally generated antigen + filtered antibody
31
What is the secondary etiology of Membranous Nephropathy?
- SLE, hepB, occult carcinoma
| - Rx: gold preparations, penicillamine
32
What is the secondary pathogenesis of Membranous Nephropathy?
- in-situ formation in sub-podocyte epithelial space
- Recruits complement, but NOT nephritic because sheds complement into urine and also is sub epithelium -- no contact w/ inflammatory cells
33
What is the clinical presentation of Membranous Nephropathy?
- Most common cause of nephrotic syndrome in caucasians, males
- No serological abnormalities
- Hypertension
- Azotemia
- Thromboembolic complications
34
What is the light microscopy characteristics of Membranous Nephropathy?
- Thickening of capillaries
- Thickening of mesangial matrix
- Subepithelial deposits (thick GBM)
35
What is the immuno profile of Membranous Nephropathy?
- IgG+
- C3+
- C4+ (not nephritic)
- lumpy, bumpy fluorescence
36
What is the EM profile of Membranous Nephropathy?
- layer of subepithelial deposits
- Retraction and effacement of foot processes
- Spikes of GBM on capillary walls
37
How do you treat Membranous Nephropathy?
- Give ACE inhibitor for BP & proteinuria
| - Cytotoxic + steroids
38
What is the prognosis for Membranous Nephropathy?
- Spontaneous remission (40%)
- Progressive renal failure (30%)
- Persistent proteinuria +/- renal failure
39
What are the buzz words for Membranous nephropathy?
Diffuse thickening of capillary walls
40
What disease does "diffuse thickening of capillary walls" describe?
Membranous nephropathy
41
What glomerular disease is associated with subendothelial deposits?
Membranoproliferative Glomerulonephritis
42
What are the 2 types of Membranoproliferative Glomerulonephritis?
Type 1 - Most common
| Type 2 - Dense Deposit disease
43
What is the etiology of Membranoproliferative Glomerulonephritis Type I?
- Idiopathic
- Secondary to hepC > hepB infections
- Damage occurs from activation of both complement pathways
44
What is the pathogenesis of Membranoproliferative Glomerulonephritis?
Damage = cytokines/autocoids released w/ complement >> increase endothelial adhesion to circulating immune complexes >> inflammation
45
Type I Membranoproliferative Glomerulonephritis is characterized by subendothelial deposits caused by endothelial injury. What are three causes of endothelial injury in general?
- Deposition of immune complexes in subendothelial space
- Thrombotic microangiopathies
- Entrapment of paraproteins (myeloma, plasma cell)
46
What is the clinical presentation of Type I Membranoproliferative Glomerulonephritis?
- Nephritic syndrome + Nephrotic syndrome
- rapidly progressing glomerulonephritis
- anti-hepC antibody
- low C3 complement levels
47
What is the immunohistochemistry profile of Type I Membranoproliferative Glomerulonephritis?
C3 + Ig
48
What is the EM profile of Type I Membranoproliferative Glomerulonephritis?
- Thickened BM
| - Hypercellular: expansion of capillaries and mesangial matrix, thickening of capillary loops
49
What is the LM profile of Type I Membranoproliferative Glomerulonephritis?
Capillary wall >> tram track appearance
| --- duplicated basement membrane b/c of immune complex deposits and infiltrating mesangial cells
50
What is the treatment for Membranoproliferative Glomerulonephritis?
No concensus on treatment
51
What is the prognosis for Membranoproliferative Glomerulonephritis?
- Spontaneous remission may occur
| - Usually slow progression to end stage renal disease
52
What autoantibody is associated with Type 2 Membranoproliferative Glomerulonephritis?
C3NeF - C3 Nephritic Factor
53
What is another name for Type 2 Membranoproliferative Glomerulonephritis?
Dense Deposit Disease
54
What is the mechanism of Type 2 Membranoproliferative Glomerulonephritis?
C3NeF autoantibody binds to C3 convertase (C3Bb) preventing degradation of C3 convertase >> constant, low level complement activation
55
Type 1 vs. Type 2 Membranoproliferative Glomerulonephritis. Which has a worst prognosis?
Type 2 has a worst prognosis than Type I
56
What is the clinical presentation of Membranoproliferative Glomerulonephritis Type II?
- Similar to Type I
- Macular deposits in eye
- partial lipodystrophy (loss of upper body cutaneous fat)
- common in transplant patients
57
What is the immuno profile of type 2 Membranoproliferative Glomerulonephritis?
C3 deposition "lining" caps
| NO Ig
58
What is the LM characteristics of type 2 Membranoproliferative Glomerulonephritis?
Same as Type I >> tram track appearance
59
What is the EM profile of Type 2 Membranoproliferative Glomerulonephritis?
- Splitting of capillary BM from deposits
| - "Split" = dense deposits + mesangial cytoplasm
60
What is the buzz word for Type 2 Membranoproliferative Glomerulonephritis?
Ribbon-like appearance
61
What disease is associated with the buzz word "ribbon like appearance"?
Type 2 Membranoproliferative Glomerulonephritis
62
What disease is associated with mesangial deposits of Galactose deficient IgA1?
IgA Nephropathy (Berger's Disease)
63
What is the etiology of IgA Nephropathy?
1-2 days post URI or GI infection
- -- The exact etiology is unknown
- -- We do know that IgA is the main immunoglobin of MUCOSAL SURFACES
- -- both pharyngeal & GI have large mucosal surfaces
64
What is the pathogenesis of IgA Nephropathy?
URI or GI infection >> underglycosylation of O-linked glycans of IgA1 >> N-linked glycan recognized by circulating immune complexes >> mesangial deposits of Galactose deficient IgA1
65
What is Secondary IgA Nephropathy called?
Henoch-Schonlein Purpura
66
What diseases are associated with Henoch-Schonlein Purpura?
GI gastroenteritis + Liver disease
- Cirrhosis
- Irritable bowel disease
- Celiac disease
67
What is the clinical presentation of IgA Nephropathy?
- Most common primary glomerulonephritis
- 1-2 days post URI
- hypertension
- macroscopic hematuria
- Nephritic > Nephrotic presentation
68
What are the risk factors for IgA Nephropathy?
- Proteinuria/edema
- decreased GFR
- older age
- HPTN
- crescent (rapidly progressive glomerulonephritis)
69
What is the LM profile of IgA Nephropathy?
- Mesangioproliferative
| - May be crescent formation
70
What is the immuno profile of IgA Nephropathy?
IgA+ (only in 50% of patients)
71
What is the EM profile of IgA Nephropathy?
Mesangial deposits
72
What's the name for systemic Anti-glomerular basement membrane disease?
Goodpasture's Syndrome
73
What's the etiology of Goodpasture's Syndrome?
Autoantibodies against alpha-3 subunit of Type 4 collagen (non-collagenous portion)
74
What are the diseases associated with Goodpasture's Syndrome?
- Pulmonary hemorrhage
- Renal failure
- Disproportional anemia
- Arthritis
- HPTN
75
What is the prognosis of Goodpasture's Syndrome?
- rapid development of kidney failure
- glomerulosclerosis
- Crescent formation (rapid progresive glomerulonephritis)
76
What is the clinical presentation of Goodpasture's syndrome?
- Nephritic syndrome
- no correlation between titers and disease activity
- might confuse with Wegener's but more azotemia in goodpasture's
- Goodpasture's is seen in smokers or in cases where there is already some damage to lung--- this is because the antibodies have to be able to access the collagen in that tissue
77
What is the LM profile of Goodpasture's syndrome?
necrotizing
crescenting
--- crescenting is proliferation of BC parietal cells into urinary space
78
What are seen in the lungs of patients with Goodpasture's syndrome?
Full of hemosiderin and fluid accumulation from hemorrhage
79
What is the immunohistochemistry profile of Goodpasture's syndrome?
Linear anti-GBM IgG appearance
80
What is the treatment for Goodpasture's Syndrome?
Corticosteroids
Plasma exchange
Cytotoxic drugs
81
What what is the pathogenesis of Rapidly Progressive Glomerulonephritis (crescentic)?
Accumulation and proliferation of parietal cells >> compress glomerular tuft >> renal failure
82
How does Rapidly Progressive Glomerulonephritis (crescentic) cause renal failure?
Allows RBC, WBC, Fibrinogen and other plasma components to enter the urinary space >> increase proliferation of mononuclear cells and parietal cells
83
How is Rapidly Progressive Glomerulonephritis (crescentic) initially characterized?
Initially characterized as segmental proliferative necrotizing lesions >> cellular crescent >> fibrocellular crescents >> fibrous crescents
84
What diseases are most commonly associated with Rapidly Progressive Glomerulonephritis (crescentic)?
Goodpasture's
Wgener's
Other ANCA+ disease
85
What is the clinical presentation of Rapidly Progressive Glomerulonephritis (crescentic)?
Nephritic
Rapid loss of renal function
Oliguria
Death with no treatment
86
What are the 3 types of Rapidly Progressive Glomerulonephritis (crescentic)?
Type I - Linear
Type II - Granular
Type III - Pauci-Immune
87
What are the differences between the 3 types of Rapidly Progressive Glomerulonephritis (crescentic)?
Type I - Linear
--- Usually anti-GBM diseases
Type II - Granular
- -- Usually immune complex disease
- -- Lumpy, bumpy w/necrosis & mesangial proliferation
Type III - Pauci-Immune
- -- little immune deposition: negative immune
- -- Wegener's and ANCA-associated vasculitis
88
What are the LM/EM profile of Rapidly Progressive Glomerulonephritis (crescentic)?
Look for polys and fibrin
89
What's another name for Hereditary Nephritis?
Alport's Syndrome
90
What is the genetics of Hereditary Nephritis (Alport's Syndrome)?
```
Defective Alpha-5 collagen Type 4
- X-linked (alpha-5)
Can also be AR, AD
- Ch 13: alpha 1,2
- Ch 2: alpha 3,4
```
91
What is the pathogenesis of Hereditary Nephritis (Alport's Syndrome)?
Collagen 4A5 mutation prevents collagen heterotrimer formation
92
Where is collagen Type 4 - Alpha 5 located?
GBM, lens of the eye & cochlea
93
What other disease can Hereditary Nephritis (Alport's Syndrome) protect you against?
Cool fact: Patients with Ch 2 (alpha 3 mutation of Collagen Type 4) are protected from Goodpasture's Disease!
94
What is the clinical presentation of Hereditary Nephritis (Alport's Syndrome)?
Males have persistent hematuria, proteinuria, end stage renal disease, sensoneural hearing loss, lens abnormalities, platelet defects, esophageal defects
95
What does the SEEK pneumonic stand for in Hereditary Nephritis (Alport's Syndrome)?
Skin
Eyes
Ears
Kidney
96
How are heterozygous females with Hereditary Nephritis (Alport's Syndrome) affected?
may have hematuria and thin basement membranes
97
What is the EM profile of Hereditary Nephritis (Alport's Syndrome)?
- Splitting of lamina densa
- Basket weave appearance
- -- split basement membrane
- -- can also do skin biopsy to see same collagen
98
What is the etiology of Thin Basement Membrane Disease?
Defect in alpha 3,4 Type 4 collagen
99
What is the pathogenesis of Thin Basement Membrane Disease?
GBM thickness is reduced about 1/2 normal size
100
What is the inheritance pattern of Thin Basement Membrane Disease?
Autosomal dominant
101
What is the clinical presentation of Thin Basement Membrane Disease?
Usually diagnosed at routine checkup, benign as long as heterozygous
102
What is another name for Thin Basement Membrane Disease?
Benign Familial Hematuria
103
What is the prognosis for Thin Basement Membrane Disease patients?
If compound or homozygous = bad prognosis
104
What is the general pathogenesis of vascular disorders?
- Inflammation of blood vessels (vasculitis) >> loss of thromboresistance (pro-clot formation seen in thrombotic microangiopathies)
105
What is the pathogenesis of Poalyarteritis nodosa?
MEDIUM VESSEL disease >> ANCA negative >> fibrinoid necrosis of vasculature >> glomerular ischemia
106
What are the important facts distinguishing Pauci immune Glomerulonephritis?
Crescent glomerulonephritis w/negative immunofluorescence
| --- often ANCA-positive with extrarenal findings
107
What is the pathogenesis of ANCA-Associated Glomerulonephritis?
Pathogeneic contact & adhesion to vascular endothelium >> creates target for inflammatory cells
108
What causes the loss of thromboresistance in ANCA-Associated Glomerulonephritis?
ANCA can bind to PMN toxic component (PR3) preventing inactivating proteins (alpha-1-antitrypsin) from inactivating
--- deposition of ANCA-PR3 on endothelium causes loss of thromboresistance
109
What are the 2 types of ANCA-Associated Glomerulonephritis?
cANCA = cytoplasmic; proteinase 3 target
----- WEGENER'S!
pANCA = perinuclear; lysosomal MPO target
110
What is the immuno profile of ANCA-Associated Glomerulonephritis?
cANCA - fine cytoplasmic staining
| pANCA - perinuclear staining
111
What are the similarities and differences between Goodpasture's and Wegner's Gramulomatous?
- Both have lung involvement
| - Wegener's has fewer presentations of azotemia
112
What is the etiology of Wegner's Gramulomatous?
cANCA positive
| - anti-nuclear cytoplasmic antibodies for Proteinase 3
113
What is the prognosis of Wegner's Gramulomatous?
80-90% mortality if untreated
114
What is the clinical presentation of Wegner's Gramulomatous?
URI, rhinnorrhea, sinusitis, nasopharyngeal irritation, LUNG INVOLVEMENT, nephritic symptoms, granulomas in lungs, nose, and sinus, MULTIPLE SKIN LESIONS
=== sinopulmonary renal syndrome
+ arthritis, arthralgia, myalgia, fatigue
115
What is the LM profile of Wegner's Gramulomatous?
Granulomatous vasculitis; renal may show segmental issue >> crescent
116
What is the IF profile of Wegner's Gramulomatous?
Pauci-immune glomulonephritis (crescent) Type 3
117
What is the treatment for Wegner's Gramulomatous?
Oral cyclophhosphamide
steroids
plasma exchange
118
What is the pathogenesis of Thrombotic Microangiopathy?
endothelial cell damage >> Loss of thromboresistance of endothelial cells >> widespread microvascular thrombosis >> deposition of platelet and fibrin thrombi in lumen
119
What is the etiology of Thrombotic Microangiopathy?
Endothelial cell damage from:
- verotoxin from Ecoli H7
- auto-antibodies
- chemotherapy
- radiation
120
What diseases are associated with Thrombotic Microangiopathy?
- TTP - vWF disease
- Childhood hemolytic uremic syndrome
- --- Shiga toxin
121
What is clinical presentation of Thrombotic Microangiopathy?
```
Bleeding
MAHA
Thrombocytopenia
Children for HUS
--- McDonald's >> kids (HUS) like hamburgers (Shiga/Ecoli) and onion rings (light microscopy) but don't want thrombi (TTP/DIC)
```
122
What is the endothelial appearance of Thrombotic Microangiopathy?
Onion skin appearance
Swelling
Microthrombi
123
What is the DDx of TTP vs. DIC?
- - TTP = normal PT and PTT because this ia a platelet disorder, not clotting disorder
- - DIC has prolonged PT/PTT
124
What is the treatment for Thrombotic Microangiopathy?
- Dialysis for HUS
| - Plasmapheresis for TTP
125
What is the etiology of Lupus Nephritis?
SLE is a system disease caused by autoimmune antibodies (ANCA, Anti-dsDNA)
126
Name and distinguish the 4 types of Lupus Nephriits?
```
Lupus Nephriits Type I
Lupus Nephriits Type II
---- mesangial proliferative
---- increased mesangial matrix & cells
Lupus Nephriits Type III
---- focal proliferative
---- often w/ crescent (rapid prog. GN)
Lupus Nephriits Type IV
---- diffuse proliferative
---- worst prognosis
```
127
What is the clinical presentation of Lupus Nephriits?
Systemic disease sparing no organ system, begins with arthritis, rash on face, renal failure; Brazil
128
What is the immuno profile of Lupus Nephriits?
- Subendothelial deposits
- Full House / Kitchen sink
- -- contains positive signals for C3, C4, IgA, IgG, IgM
- -- has eerything
129
What is the treatment for Lupus Nephriits?
FDA approved: aspirin, glucocorticoids, hydroxychloroquine
| Immunosuppressive: Cyclophosphomide mycophenolate mofetil
130
What is the etiology of Scleroderma systemic sclerosis?
unknown
131
What is the pathogenesis of Scleroderma systemic sclerosis?
Connective tissue fibrosis
| Vascular occlusion of microvasculature
132
What are the 2 types of Scleroderma systemic sclerosis?
```
(LC) Limited cutaneous
- few constitutional symptoms
- severe Raynaud's finding
(DC) Diffuse cutaneous
- present at 5 years
- many constitutional symptoms (heart, lungs, kidneys)
- Mild Raynaud
```
133
What is the clinical presentation of Scleroderma systemic sclerosis?
Females, AA, mild renal involvement, HPTN, proteinuria
134
What is the risk factors for Scleroderma systemic sclerosis?
Scleroderma renal crisis
Arterial HPTN
Oliguric renal failure
Luminal narrowing of arcuate arteries
135
What is the LM profile for Scleroderma systemic sclerosis?
Luminal occlusion
systemic changes in blood vessels
- onion skin appearance
136
What does the glomerulus look like in a patient with Scleroderma systemic sclerosis?
No inflammation
Ischemia
Increased glomerular hydrostatic pressure from increased resistance
137
What is the treatment for Scleroderma systemic sclerosis?
ACE inhibitors for renal crisis
138
What is cause of sickling in Sickle Cell Nephropathy?
RBC prone to sickling in hypoxic, hypertonic, acidic medulla
139
What is the mechanism of RBC sickling's effect on medullary function in Sickle Cell Nephropathy?
Medulla becomes hypoxic as it descends >> deoxygenated HbS sickles >> increase polymerization of RBC >> vasa recta become attenuated (trait) or absent (SCD) >> loss of medullary funciton >> loss of ability to dilute and concentrate urine
140
What is the mechanism of Sickle Cell Nephropathy?
increased GFR + increased RPF = hyperfiltration >> proximal tubule increases function >> hyperfiltration persists from birth till 40s when disease presents w/ low GFR
141
Why would some patients with no other associated renal dysfunction have milder form of Sickle Cell Nephropathy if both are homozygous?
Disease affects mainly juxtamedullary nephrons; cortical nephrons tubular system barely enters hypoxic medulla
142
What is the incidence of Sickle Cell Nephropathy?
- decline in 40s-50s when low GFR
- 4-12% of patients >> ESRD
- other complications can kill before (CVD)
143
What is the clinical presentation of Sickle Cell Nephropathy?
60% microalbuminuria
20% proteinuria
Hematuria
Hyperphosphatemia
144
What is the histopathology of Sickle Cell Nephropathy?
Due to increased GFR (hemodynamic)
- Early
- --- glomerular hypertrophy, hemosiderin (transfusions), focal damage
- Later
- --- interstitial inflammation + tubular atrophy
- End stage
- --- Glomerular enlargement, FSGS
- Renal artery thrombosis
- Microthrombi of glomerulus an dvasa recta
- Glomerulosclerosis, mesangial expansion
- papillary necrosis - less blood flow down medulla -- also seen in DM, chronic pyelonephritis, and NSAID abuse TIN
145
What are the 4 types of Amyloidosis?
1. AL Amyloidosis (Primary)
2. AA Amyloidosis (Secondary- systemic)
3. Abeta2M Amyloidosis
4. Hereditary Amyloidosis
146
What is the classification of the 4 types of Amyloidosis?
Primary: idiopathic, B-cell abnormality, AL
Secondary: chronic inflammatory disease (RA), AA (inflammatory amyloid protein)
Familial: inherited mutation, AA, ATTR, Acys, Abeta (Alzheimer protein)
Isolated (focal) Amyloidosis: deposits in single tissue/organ, Abeta, AiAPP (diabetes), ATTR
147
What is the mechanism of all Amyloidosis types?
Interstitial deposits of insoluble B-pleated fibrils
| --- disease specific fragment w/ B-pleated conformation
148
How are pathogenic proteins misfolded in Amyloidosis?
- Intrinsic pathogenic property of protein
- single amino acid replacement (familial)
- proteolytic remodeling of a protein precursor
149
What is the consequence of misfolded pathogenic proteins in amyloidosis?
Enlarged kidney from deposits
Vascular involvement
Interstitial deposits >> fibrosis >> tubular damage (think nephrogenic diabetes, ion imbalance)
150
How do you diagnose Amyloidosis?
SPEP/IF or Serum Light Chain Assay
151
How do you treat Amyloidosis?
Eprodisate - limits interaction btw GAG + Amyloid
| Low dose melphalan/dexamethasone OR transplant
152
What is the overall morphology of Amyloidosis?
- Homogenous + glassy appearance
- Congo red >> apple green bifringence
- Major components:
- --- Fibrillogenic protein (B-pleat) + Amyloid P (donut) + PG (Heparan Sulfate) + Apoprotein E
153
Is Amyloidosis nephritic or nephrotic?
NEPHROTIC - non-inflammatory
154
What is primary Amyloidosis called?
AL Amyloidosis
155
What is the etiology of AL Amyloidosis?
Secondary to multiple myeloma, B-cell lymphoma, plasma cell diseases
156
What is the mechanism of AL Amyloidosis?
Plasma cell light chain (lambda >>>kappa)
157
What is the clinical presentation of AL Amyloidosis?
64 y/o
Weakness, weight loss, nephrotic syndrome
Renal insufficiency, Bence Jones (proteinuria)
Enlarged kidneys
Myocardial dysfunction, sick sinus syndrome
Bleeding diathesis
158
What is secondary Amyloidosis called?
AA Amyloidosis (systemic)
159
What is the etiology of AA Amyloidosis?
Secondary to chronic inflammatory disease (RA, Familial Mediterranean Fever)
160
What are the affected organs in Amyloidosis?
Kidney + GI malabsorption
161
What is the pathogenesis of AA Amyloidosis?
Serum amyloid A (SAA) increased w/ inflammation >> Amyloid Enhancing Factor (AEF) changes SAA processing by macrophages and endothelial cells >> BM disturbances are required so SAA can bind >> apoE + SAA + AEF + BM >> amyloid AA
162
What is the clinical presentation of AA Amyloidosis?
```
Chronic inflammatory condition
Renal insufficiency
GI insufficiency
+Kidney biopsy
Vascular (coronary artery, renal)
```
163
What is the name of the Amyloidosis associated with diabetes?
Abeta2M Amyloidosis
| --- will use B for beta from now on
164
What is the precursor for AB2M Amyloidosis called?
B2 Microglobulin
165
Which patients have elevated B2 Microglobulin?
Patients with chronic dialysis
166
What is the clinical presentation of patients with AB2M Amyloidosis?
Deposits in bones and joints
167
What is the inherited form of Amyloidosis called?
Hereditary Amyloidosis
168
What are the test results for Hereditary Amyloidosis?
Negative for heavy/light chains
| Positive for fibrinogen, transthyretin, apolipo, lysozyme
169
How do you treat patients with Hereditary Amyloidosis?
Liver transplant
170
What is another name for light chain disease?
Non-amyloid monoclonal Ig deposition disease (MIDD)
171
What makes the etiology of light chain disease (MIDD) different from Amyloidosis?
Not just the B-pleated sheet, entire Ig
| -- Kappa >> lambda
172
What makes the diagnosis of light chain disease (MIDD) different from Amyloidosis?
Light chain disease
- neg Congo red (B-sheet is still in Ig; no fibrils)
- No fibrillar organization
- precipitation of light chains
173
What is the clinical presentation of Light Chain disease, nephritic or nephrotic?
Nephrotic
174
What is the clinical presentation of Light Chain disease?
```
Proteinuria + renal failure (nephrotic-like)
HEpatomegaly
CVD (CHF, conduction disturbance)
Peripheral neuropathy
GI disturbances
Pulmonary nodules
Sicca (Sjogren's) syndrome
```
175
What is the morphology of light chain disease?
Nodular glomerulosclerosis (classic)
Expansion of mesangial matrix
Light chain deposits in glomerulus, tubules and mesangial matrix
176
What are the 2 types of virus associated kidney diseases?
HIV-associated Nephropathy
| Cryoglobulinemia
177
What is the pathogenesis of HIV-associated Nephropathy?
direct infection from HIV-1 of renal epithelial cells
178
What are the risk factors for HIV-associated Nephropathy?
The infection must occur in a genetically susceptible host
- Common in African Americans w/o ApoL1 (Ch.22) allele
- Mutation in ApoL1 protects against Trypanosoma brucie rhodesiese (African sleeping sickness)
179
What is the clinical presentation of HIV-associated Nephropathy?
Late stage HIV with rapid onset of proteinuria
| - no edema, no HPTN
180
What is the morphology of HIV-associated Nephropathy?
```
Collapsing FSGS
Tubular dilation (full of protein-like material)
Podocyte de-differentiation and proliferation
```
181
Name diseases associated with proximal tubule defects
Hereditary Renal Glucosuria
Cystinuria
Hypophosphatemia
Hypo/Hyperuricemia
182
What is the etiology of Hereditary Renal Glucosuria?
Autosomal recessive; 1/20,000
| Mutation in SGLT2 glucose transporter
183
What is the pathogenesis of Hereditary Renal Glucosuria?
Defective glucose reabsorption >> glucose concentration overcomes threshold >> renal glucosuria
184
What are the 2 renal glucose transporters?
SGTL1 - found on enterocytes, unaffected
| SGTL2
185
People with what disease would benefit from having Hereditary Renal Glucosuria?
We would want SGLT2 mutation in diabetics - we give SGTL2 inhibitors to diabetic patients
186
What is the etiology of Cystinuria?
Mutation in brush border transporter of CYSTINE, ORNITHINE, LYSINE, ARGININE
187
What is the mechanism of Cystinuria
Defective amino acid reabsorption
188
What is found in the urine of patients with Cystinuria?
cystine stones, cystine crystals (hexagonal)
189
What is the mechanism of Hypophosphatemia?
Defective phosphate reabsorption
190
What are the inherited causes of Hypophosphatemia?
1. X-linked Hypophosphatemia (PHEX mutation)
- --- Rickets in kids; osteomalacia in adults
2. Autosomal Dominant Rickets (FGF-23 mutation)
3. Autosomal Recessive Hypophosphatemic Rickets (FGF-23 OR Na/Pi IIc transporter)
191
What are the acquired causes of Hypophosphatemia?
1. Oncogenic Hypophosphatemic Osteomalacia (increased FGF-23 production)
192
What is the pathogenesis of Hypophosphatemia?
- PHEX mutation decreases FGF-23 degradation
- increased FGF-23 down regulates phosphate transporter activity (not a mutation in transporter) >> FGF lowers calcitrol = increases PTH >> lowers P = hpophosphatemia >> also inhibits activation of vit. D
193
What are the two diseases characterized by defective uric acid handling in the kidney?
Hypouricemia
| Hyperuricemia
194
What is the mechanisms of hypo and hyperuricemia?
--- Uric acid ---
Decreased reabsorption = hypouricemia
Defective secretion = hyperuricemia
195
What is the generalized PT dysfunction in Faconi's syndrome, acquired vs. inherited?
acquired > inherited
196
What are the possible mechanisms of Faconi's syndrome?
- Defecting binding of Na to transport proteins
- defecting inserting of carriers
- Leaky membrane tight junctions
- inhibit Na/K ATPase
- impaired mitochondria energy generation
197
What are the metabolic abnormalities associated with Faconi's syndrome?
1. aminoaciduria
2. glucosuria (normal serum glucose)
3. Hypophosphatemia (multifactorial: decreased Na/P carrier, decreased Vit D)
4. Increased bicarb excretion = metabolic acidosis
5. Hypokalemia (more delivery to distal tubule)
6. Uricosuria
198
What is the clinical presentation of Faconi's syndrome?
```
Polyuria/polydipsia form osmotic diuresis
Volume depletion
Cardiac issues (K+)
Proteinuria
Rickets
Renal stones
Growth retardation
```
199
What are the drug-induced etiologies of Faconi's Syndrome?
Tenofovir (anti-HIV)
Lead
Toluene (toxin)
Aristolochic Acid (weight loss)
200
What types of diseases are associated with loop of Henle and distal tubule defects?
Sodium disorders
Hypokalemia
Hyperkalemia
Renal tubular acidosis
201
Name the 3 Sodium disorders?
Bartter's Syndrome
Gittelman's Syndrome
Liddle's syndrome
202
What is the etiology of Bartter's Syndrome?
Mutation in Na, k, 2Cl in TALH
| - Autosomal recessive
203
What is Neonatal Bartter's Syndrome?
Polyhydraminous: high PGE2, give COX-1
| -- volume depletion >> excess fetal urine >> failure to thrive
204
What is the clinical presentation of Bartter's syndrome?
- Low blood Ca, Mg, Cl, K - metabolic alkalosis
- Na wasting disorder
Increased K+ and H+ secretion
----- due to increased luminal negative transepithelial potential downstream due to increased Na delivery and increased ENaC from aldosterone
- High renin, aldosterone - volume depletion
- crave pickle juice
205
How do you treat Bartter's syndrome?
K+ supplements
Mg supplements
high salt intake
206
What is the etiology of Gittelman's Syndrome?
Mutation in thiazide sensitive NCCT in DCT
- - autosomal recessive
- - Na wasting disorder
207
Bartter's vs. Gittelman's, which is more severe?
Patients have more normal growth with Gittelman's compared to Bartter's because less sodium in wasted with this mutation
208
What are the findings in Gittelman's syndrome?
- Hypochloremic, hypokalemia metabolic alkalosis
- Low Mg
- Hypercalcemia (b/c PTH effect)
- High renin, aldosterone
209
What is the etiology of Liddle's Syndrome?
ENaC channel beta/gamma mutations
| Autosomal dominant
210
What is the pathogenesis of Liddle's Syndrome?
ENaC channel is always open
- gain of function mutation
- low renin and aldosterone
- high Na will increase lumen negative transepithelial charge >> low K+ retention >> hypokalemia
- high K+ in lumen will provide substrate to alpha-intercalated K/H+ATPase >> increase H+ excretion >> metabolic alkalosis
211
What is the clinical presentation of Liddle's Syndrome?
- Hypertension
| - Mirror image of Pseudohypoaldosternism Type I
212
Name the three diseases that are associated with Hypokalemia
1. Primary and Secondary Hyperaldosteronism
2. Glucocorticoid Remediable Aldosteronism (GRA)
3. Apparent Mineralcorticoid Excess (AME)
213
What is the etiology of primary Hyperaldosteronism?
Adrenal tumors
214
What is the etiology of secondary Hyperaldosteronism?
dehydration, pyloric stenosis (Barfer's), Bartter's/Gittelman
215
What are the clinical findings in dehydration and pyloric stenosis Hyperaldosteronism??
- Pyloric stenosis is common in first born males with increase vomit >> dehydration >> increase aldosterone
216
What are the clinical findings in Bartter's/Gittelman Hyperaldosteronism?
- increase urinary chloride because this is a genetic defect in Cl- transport
- important for differentiating between these secondary causes for hyperaldosteronism
217
What is the pathogenesis of Glucocorticoid Remediable Aldosteronism (GRA)?
Recombination of aldosterone synthase and 11-Beta-hydroxy-dehydrogenase >> increase aldosterone in response to stress
218
What are the clinical findings in Glucocorticoid Remediable Aldosteronism (GRA)?
- low renin -- aldosterone not created by RAAS
- increase Na >> increase lumen negative transepithelial charge >> low K+ retention >> increase hypokalemia
- increase K+ in lumen will provide substrate to alpha-intercalated K+/H+ATPase >> increase H+ excretion >> metabolic acidosis
219
What is the treatment for Glucocorticoid Remediable Aldosteronism (GRA)?
Glucocorticoids
220
What is the pathogenesis of Apparent Mineralcorticoid Excess (AME)?
Mutated enzyme 11BHD2 >> increased activation of aldosterone receptor >> increase ENaC
221
What is the function of the enzyme 11BHD2?
Enzyme 11-Beta-hydroxy-dehydrogenase 2 exists to prevent glucocorticoids from binding to aldosterone receptors
222
What happens to the mutated enzyme 11BHD2 in Cushing's Syndrome?
In cases of excess glucocorticoids (Cushing's Syndrome), 11BHD2 is overwhelmed
223
What is the clinical findings in Apparent Mineralcorticoid Excess (AME)?
- low renin, aldosterone
- increase Na will increase lumen negative transepithelial charge >> low K+ retention >> increase hypokalemia
- increase K+ in lumen will provide substrate to alpha-intercalated K+/H+ATPase >> increase H+ excretion >> metabolic alkalosis
224
What is the treatment for - increase K+ in lumen will provide substrate to alpha-intercalated K+/H+ATPase >> increase H+ excretion >> metabolic acidosis?
Glucocorticoids
225
What are the 3 diseases associated with hyperkalemia?
1. Hypoaldosteronism
2. Pseudohypoaldosteronism Type I
3. Pseudohypoaldosteronism Type II
226
What are the 3 diseases that cause Hypoaldosteronism?
- congenital adrenal hypoplasia
- congenital adrenal hyperplasia
- autoimmune disease
227
What diseases are associated with hypoaldosteronism and adrenal insufficiency?
- Congenital adrenal hypoplasia
| - Addison's disease
228
What is the main problem in both congenital adrenal hypoplasia and Addison's disease?
no aldosterone
229
What is congenital adrenal hyperplasia and how is it related to Cushing's syndrome?
- disorder of steroid synthesis pathway (21 hydroxylase most common)
- also could create excess cortisol activation of aldosterone receptor as in cushing's syndrome
230
What are 3 autoimmune diseases associated with Hypoaldosteronism?
IDD
Hypothyroidism
Addison's Disease
231
What is the pathogenesis of hypoaldosteronism?
- low aldosterone and decreased activation of ENaC >> decrease lumen negative transepithelial charge >> increased K+ retention >> hyperkalemic metabolic acidosis
232
What is the etiology of Pseudohypoaldosteronism Type I?
- AD mutation in mineralcorticoid receptor OR
| - AR ENaC mutation (loss of function > stuck closed > opposite of Liddle)
233
What is the dysfunction in Pseudohypoaldosteronism Type I?
Tubular disorder - have aldosterone, but doesn't work right
234
What are the clinical findings in Pseudohypoaldosteronism Type I?
- high renin to high Na retention
- Hyperkalemia, hyponatremia (aldosterone dysfunction)
- prone to volume depletion
235
What are 2 other names for Pseudohypoaldosteronism Type II?
Gordon's syndrome
| Chloride shunt syndrome
236
What is the etiology of Pseudohypoaldosteronism Type II?
Mutation in WNK 4 (regulator of NCCT) or WNK1 (regulator of WNK 4) of NCCT
237
What is the pathogenesis of Pseudohypoaldosteronism Type II?
- high Na reabsorption in DCT
- This is proximal compared to other hyperkalemic diseases, which means you have less delivery of Na to the CD, so no extra excretion of K+
- hyperkalemia
238
What are the clinical findings in Pseudohypoaldosteronism Type II?
- low RAAS b/c increased Na reabsorption
- hyperkalemic
- hyperchloremic
- metabolic acidosis
- mirror image of Gittelman syndrome
239
What is the treatment for Pseudohypoaldosteronism Type II??
thiazide diuretics
240
What are the 3 types of Renal Tubular Acidosis? (stones, bones, aldosterone)
1. Type I RTA - Classical distal RTA
2. Type 2 RTA - Proximal Tubule defect
3. Type 4 RTA - Secondary to hypoaldosteronism
241
What is the major dysfunction in Type I RTA - Classical distal RTA?
Inability of distal tubule to secrete H+
242
What diseases are associated with Type I RTA - Classical distal RTA?
Nephrolithiasis (stones) and amphotercin
| Failure to thrive
243
Is the K+ high or low in Type I RTA - Classical distal RTA?
Hypokalemia - no H+ secretion, no K+ reabsorption
244
What is the major dysfunction in Type 2 RTA - Proximal Tubule defect?
Inability of PT to resorb HCO3-
245
What diseases are associated with Type 2 RTA - Proximal Tubule defect?
Faconi's Syndrome
| Ricket's and multiple myeloma (bones)
246
Is the K+ high or low in Type 2 RTA - Proximal Tubule defect?
Hypokalemia
247
What is the pathogenesis of Type 4 RTA - Secondary to hypoaldosteronism?
low aldosterone >> low Na reabsorption >> high K+ retention >> hyperkalemia
248
What is the primary defect in Type 4 RTA - Secondary to hypoaldosteronism?
considered a distal tubule issue, but actually has to do with NH3 secretion proximally
249
How does hyperkalemia lead to low NH4 formation in Type 4 RTA - Secondary to hypoaldosteronism?
hyperkalemia >> increased K+ movement intracellularly >> increase H+ movement out of cell >> increase pH in cell >> decrease NH3 production to restore pH >> decrease NH4 formation
250
For all RTA types, are the plasma and urinary anion gaps normal?
All RTA types are NORMAL plasma anion gap & positive urinary anion gap acidosis
251
What are the 4 tests for distinguishing RTA types?
1. Fractional Excretion of Bicarb
2. Urine pH
3. Urine anion Gap (UNa + UK+ - UCI-)
4. U-B PCO2
252
For the Fractional Excretion of Bicarb test, which RTA type can you identify?
- high HCO3 excretion in Type 2
| - normal in other types
253
For the urine pH test, which RTA type can you identify?
pH < 5.5 in type 2
- - because defect is proximal before acidification
- - pH > 5.5 in other types
254
Is the urine ion gap test + or - in RTA? Why?
Positive
- in RTA, low H+ secretion >> no NH4+
- therefore, Na + K > Cl = positive
255
What are the results for a normal urine ion gap test and why?
Normally: high H+ secretion >> high NH4+
- because NH4+ is not measured in urine anion gap, and elevated NH4+ will require that Cl- increases to maintain neutrality, thus Cl > Na + K
256
How do you perform the U-B PCO2 test and what does it measure?
- Give HCO3- + acetozolamide
- HCO3- cannot be absorbed in PT
- In DT/CD it will rect with H+ >> H2O+CO2 >> measure the CO2
257
For the U-B PCO2 test, which RTA type can you identify and why?
- Normal in Type 2
| - Low in Type 1 & 4 because no H+ to react
258
What is the etiology of Papillary Necrosis?
Focal ischemia + infection
259
How does infection cause Papillary Necrosis?
Increased metabolic needs from infection / toxicity >> inflammation w/ metabolic demands >> micro/macro angiopathy induced ischemia
260
What diseases are associated with Papillary Necrosis?
UTI, diabetes, UT obstruction, analgesic nephropathy
261
What is the difference between ATN and Papillary Necrosis?
Focal ischemia in Papillary Necrosis vs. diffuse ischemia in ATN
262
What is the clinical presentation of Papillary Necrosis?
- Azotemia
- fever
- renal pain
263
What will the urinalysis show in Papillary Necrosis?
- macroscopic hematuria
| - passage of tissue shreds
264
what is another name for Pseudohyperaldosteronism?
Liddle's Syndrome
265
What is the etiology of Liddle's Syndrome (Pseudohyperaldosteronism)?
ENaC channel is always open due to beta/gamma mutations
| - autosomal dominant
266
What is the pathogenesis of Liddle's Syndrome (Pseudohyperaldosteronism)?
- low renin & aldosterone
>> high Na will increase lumen negative transepithelial charge >> low K+ retention >> high hypokalemia
>> high K+ in lumen will provide substrate to alpha-intercalated K/H+ATPase >> high H+ excretion >> metabolic acidosis
267
How do you treat Liddle's Syndrome (Pseudohyperaldosteronism)?
Triamterene or amiloride (K+ sparing ENaC inhibitors)
268
What are 3 water and salt balance disorders that are associated with edema?
1. CHF
2. Liver cirrhosis
3. Nephrotic syndrome
269
In congestive heart failure (CHF), how does low CO lead to edema?
Low CO >> low EABV >> RAAS + SNS + AVP/ADH >> increased Na + water reabsorption >> increase plasma volume >> increase vascular hydrostatic pressure >> edema
270
What is the clinical presentation of CHF?
```
Edema
bibasilar rales
Cardiac enlargement
Neck vein distention
Pulmonary edema
```
271
What is the basic 3 steps in the pathogenesis of edema in CHF?
increased plasma volume >> increased hydrostatic pressure >> edema
272
How does liver cirrhosis lead to edema?
1. increased hydrostatic pressure >> increased PV
| 2. liver failure >> low albumin >> decreased capillary oncotic pressure
273
What is the pathogenesis of liver cirrhosis?
Splanchnic vasodilation >> low EABV >> RAAS + SNS + AVP/ADH >> increased Na + water reabsorption >> increase plasma volume >> increase vascular hydrostatic pressure >> edema
274
What is the clinical presentation of liver cirrhosis?
```
liver failure
hepatosplenomegaly
concurrent persistent liver infection
hypoalbuminemia
edema
```
275
What is the pathogenesis of Nephrotic syndrome?
leaky glomerulus >> increased loss of albumin through excretion >> decreased capillary oncotic pressure
276
What is the clinical presentation of Nephrotic syndrome?
signs of kidney failure
| edema
277
What hormone directly stimulates ADH/AVP?
Angiotensin II
278
What medications stimulate ADH/AVP despite low osmolarity?
Pain & nausea meds
279
What is the pathogenesis of Hypovolemic Hyponatremia?
decrease in TBNa that exceeds decrease in TBW
280
What is the clinical presentation of Hypovolemic Hyponatremia?
Low BP
poor skin turgor
absence of dependent edema (no skin recoil)
prerenal azotemia (disproportionate increase in BUN relative to serum creatinine)
281
What are the renal causes of Hypovolemic Hyponatremia?
diuretics, aldosterone deficit
282
What are the GI causes of Hypovolemic Hyponatremia?
diarrhea, vomiting, bleeding
283
What are the skin causes of Hypovolemic Hyponatremia?
burns, sweating
284
How do you differentiate renal vs. extra-renal sodium loss?
Renal Na loss: urine Na > 20
| Extra-renal Na loss: urine Na < 20
285
Why is urine Na higher in renal vs. extra-renal causes of Na loss?
If hyponatremic, kidneys should be reabsorbing as much Na as possible, not excreting it... unless renal damage is the cause
286
What are the 2 types of hyponatremia?
Euvolemic Hyponatremia
| Hypervolemic Hyponatremia
287
In Euvolemic Hyponatremia, what is the relationship between TBW and TBNa?
- increase in TBW
| - no change in TBNa
288
What is the clinical presentation of Euvolemic Hyponatremia?
- decreased serum osmolality
- inappropriate urinary concentration
- high urinary Na
- anti-psychotic drugs
- glucocorticoid deficiency
289
What is the treatment for Euvolemic Hyponatremia?
Loop diuretics
290
How do you distinguish Euvolemic Hyponatremia and SIADH?
If there is no change in TBNa, but TBW increases >> this means that there is something released that only increases TBW = ADH/AVP
291
In Hypervolemic Hyponatremia, what is the relationship between TBW and TBNa?
increase in TBW that exceeds decrease in TBNa
| - increase in TBNa < increase in TBW
292
What is the clinical presentation of Hypervolemic Hyponatremia?
- EDEMA
- heart failure
- liver failure
- kidney failure
Diseases: CHF, liver cirrhosis, nephrotic syndrome
293
Regarding clinical symptoms, how do you differentiate acute vs. chronic hyponatremia?
Acute: has constitutional symptoms
---- nausea, malaise, headache, seizures, coma
Chronic: has few symptoms
---- cerebral edema
294
In chronic hyponatremia, how does too much water affect the brain?
too much water >> cerebral edema >> brain responds by losing intra/extra cellular solutes to make room for H2O
- -- brain adapts to chronic hyponatremia
- -- avoid demylination syndrome by altering treatment (.5 mEq/L/hr)
295
What are the 3 types of Hypernatremia?
Hypovolemic Hypernatremia
Euvolemic Hypernatremia
Hypervolemic Hypernatremia
296
What is the relationship between TBW and TBNa in Hypovolemic Hypernatremia? Use very high, high, low, very low for each and compare the two.
very low TBW > low TBNa
297
Describe the amount of TBW in Euvolemic Hypernatremia? Use very high, high, low, very low for each and compare the two.
very low TBW
298
What is the relationship between TBW and TBNa in Hypervolemic Hypernatremia? Use very high, high, low, very low for each and compare the two.
very high TBNa > high TBW
299
What is the clinical presentation of Hypovolemic Hypernatremia?
lethargy, weakness, irritable, seizure, coma
300
What is the main problem and how do you treat Hypovolemic Hypernatremia?
-- very low TBW > low TBNa
Give isotonic saline
--- volume loss (Na) is more important
301
What is the main problem and treatment for Euvolemic hypernatremia?
-- very low TBW
treat underlying cause
replace with water
302
What is the main problem and treatment for hypervolemic hypernatremia?
-- very high TBNa > high TBW
Get Na out of the body
- furosemide
- dialysis
303
What are the 2 types of diabetes insipidus?
Central diabetes insipidus
| Nephrogenic diabetes insipidus
304
What is the problem with ADH in Central diabetes insipidus compared to Nephrogenic diabetes insipidus?
Central diabetes insipidus
---- No ADH
Nephrogenic diabetes insipidus
---- ADH resistance
305
What is the etiology of Central diabetes insipidus?
trauma, tumor, congenital
306
What is the treatment for Central diabetes insipidus?
DDAVP (exogenous vasopressin)
307
What is the etiology of Nephrogenic diabetes insipidus?
V2 receptor mutation, cAMP defect
308
How do the V2 receptor mutation, and cAMP defect in Nephrogenic diabetes insipidus affect ADH?
causes ADH resistance
309
What is the clinical presentation of Nephrogenic diabetes insipidus?
```
CKD
hypokalemia
lithium
demeclocycline
sickle cell disease
PREGNANCY (VASOPRESSINASE)
```
310
How do you treat Nephrogenic diabetes insipidus?
thiazides
311
What is the method used to differentiate diabetes insipidus and primary polydipsia?
withhold water source and watch the urine osmolarity increase
312
What is the method used to differentiate central DI vs. nephrogenic DI?
give DDAVP and look for change (no change will occur in nephrogenic)
313
What molecules are low in metabolic acidosis?
very low HCO3-
| also, low CO2 by hyperventilation as compensatory mechanism
314
What anion gap do you always measure in metabolic acidosis?
Plasma anion gap
315
In metabolic acidosis, what does a high anion gap indicate?
```
unmeasured anion (MUDPILES)
Methanol
Uremia
Diabetic ketoacidosis
Propylene glycol
Inborn errors of metabolism
Lactic acidosis
Ethylene glycol
Salicyates
```
316
If the plasma anion gap is normal in metabolic acidosis, what do you measure next?
Urinary anion gap
317
What cause does a (+) urinary ion gap indicate in metabolic acidosis?
RTA
318
What cause does a (-) urinary ion gap indicate in metabolic acidosis?
diarrhea, etc.
319
In metabolic acidosis, what are the causes of decreased renal acid secretion?
- renal function impairment
- impaired NH4+ formation
- RTA Type 1 and 4 (high urinary anion gap)
320
What are the 3 general etiologies for metabolic acidosis?
1. Decreased renal acid secretion
2. Direct bicarbonate loss
3. Acid generation
321
What are 2 examples of direct bicarbonate loss in metabolic acidosis?
GI loss
| Type 2 RTA
322
What are 5 examples of acid generation in metabolic acidosis?
```
Shock
Lactic acidosis
Ketoacidosis
Aspirin
Methanol, ethylene glycol
```
323
What do you measure to determine respiratory acidosis?
pCO2
324
Is pCO2 high or low in respiratory acidosis?
very high pCO2
325
Why do you have elevated HCO3- in respiratory acidosis?
high HCO3- as compensatory kidney mechanism
326
In respiratory acidosis you have a compensatory kidney mechanism. Is this a fast or slow response?
slow process because kidney takes time to respond
327
What is an important question to ask with respiratory acidosis?
acute or chronic?
328
What causes acute respiratory acidosis?
- anything that decreases breathing = increased CO2 retention
- anesthesia
- cardiac arrest
- pneumothorax
329
What causes chronic respiratory acidosis?
- prolonged decreased breathing = high CO2 retention
- obstructive pulmonary disease
- Myopathy (chest fall dysfunction)
- barbituates, opioids, benzodiazapenes
330
Compare and contrast the changes in pH and HCO3 in acute vs. chronic respiratory acidosis?
```
Acute = high pH change & low HCO3 change
Chronic = low pH change & high HCO3 change
```
331
What is the mechanism of respiratory alkalosis?
low pCO2
| - also, low HCO3 as compensatory kidney mechanism, slow process
332
What is the most common cause of respiratory alkalosis?
anxiety (hyperventilation)
333
What causes respiratory alkalosis?
Anything that causes increased breathing = low CO2 retention
- Gram(-) bacteria (endotoxin)
- Pregnancy
- Trauma
- hypoxia
- Aspirin
334
How does pregnancy cause respiratory alkalosis?
progesterone and estrogen overstimulate the respirator center >> more CO2 is expelled per breath
335
Why do people breathe into paper bags during anxiety attacks?
Breathing into a bag gets all the expelled CO2 back in
336
What is the relationship between CO2, carbonic anhydrase reactions and HCO3- in the proximal tubule?
Think about the role of CO2 in the carbonic anhydrase related reactions in the PT.
-- More CO2 (which can diffuse into epithelial cell from basolateral side) means more substrate for that reaction >> more HCO3-
337
What is the mechanism of metabolic alkalosis?
elevated HCO3-
| - also high CO2 by hypoventilation
338
What 2 things should you always check in metabolic alkalosis?
plasma & urine ion gap
339
What is main cause of metabolic alkalosis?
Mainly loss of acid
| -- GI tract loss = vomiting/diarrhea - loss of H+
340
What are other causes of metabolic alkalosis?
- excessive urinary acid excretion
- Hyperaldosteronism
- movement of acid into cells
341
How do you determine if metabolic alkalosis is Cl responsive or Cl resistant?
Urine [Cl-] < 20 = Cl responsive
Urine [Cl-] > 20 = Cl resistant
--same concept as checking if renal vs. extra-renal
342
Name 6 causes of dehydration
- water deprivation
- extensive perspiration
- severe diarrhea
- comatose patient
- infants
- random rare "trapped in earthquake"
343
How do you treat dehydration?
Water + glucose
344
What is the mechanism of dehydration?
decrease volume in both compartments >> increase in osmolarity of both compartments, ECF, ICF
345
Outline the movement of water and changes in osmolarity in ECF/ICF when there is a loss of water from ECF.
loss of water from ECF >> relative increase of solutes in ECF >> increase in ECF osmolarity >> ICF volume moves to ECF due to osmotic gradient >> relative increase in solutes in ICF >> increase in ICF osmolarity
346
When would you give a patient an infusion of isotonic salt solution (saline infusion)?
If a patient is hypovolemic
--- may have similar findings to dehydration
Trauma patients
Bleeding
347
What is the purpose of giving a patient an infusion of isotonic salt solution (saline infusion)?
Increase ECF volume
| - no increase in osmolarity is because isotonic solutions will not change the number of osmotically active particles
348
What causes gain of water?
1. drinking large amounts of water
| 2. infusion of fluid for nutritive purposes (glucose solution)
349
In gain of water, how does addition of volume to ECF lead to decrease in ICF osmolarity?
Addition of volume to ECF >> decrease in ECF osmolarity >> while initially in ECF, it moves quickly to ICF b/c permeable cell membrane >> decrease in ICF osmolarity
350
What is Gain of Salt and what does it cause?
Excessive salt consumption >> hypernatremia (elevated plasma sodium)
351
In Gain of Water, what happens to the volume and osmolarity of ECF and ICF?
increase in volume of ECF and ICF
| decrease osmolarity
352
What is the specific steps in gain of salt that starts with excess NaCl and leads to increased ICF osmolarity
Excess NaCl remains in the ECF >> ECF osmolarity increases >> water moves from ICF to ECF >> ECF volume increases & ICF volume decreases >> ICF osmolarity increases
353
In Gain of Salt, what happens to the volume and osmolarity of ECF and ICF?
Increases ECF volume and osmolarity
Decrease ICF volume
Increase ICF osmolarity
354
What is Loss of salt and what causes it?
Hyponatremia (low plasma sodium)
| Excess water consumption after sweating
355
What is the specific steps in loss of salt that starts with low NaCl and leads to decreased ICF osmolarity
Low NaCl >> decrease ECF osmolarity >> water moves from ECF to ICF (to balance osmotic pressure) >> decrease ECF volume >> increase ICF volume >> decreased ICF osmolarity
356
In Loss of Salt, what happens to the volume and osmolarity of ECF and ICF?
osmolarity decreases overall
357
What is the cause of infusion of isotonic urea?
intentional infusion
358
What is the specific steps in infusion of isotonic urea that starts with added urea and leads to no change in osmolarity
isotonic urea infusion >> increase urea in ECF >> readily diffuses in ICF >> ICF and ECF volumes increase >> isotonic, no change in osmolarity
359
In infusion of isotonic urea, what happens to the volume and osmolarity of ECF and ICF?
increase in volume in all compartments
360
Sickle Cell Nephropathy - what 3 conditions in the medulla cause RBCs to sickle?
```
RBC are prone to sickling in
- hypoxic
- hypertonic
- acidic
Medulla
```
361
What is the mechanism of Sickle Cell Nephropathy?
medulla become increasingly hypoxic as it descends >> deoxygenated HbS sickles >> increase polymerization of RBC >> vasa recta become attenuated (trait) or absent (SCD) >> loss of medullary function >> loss of ability to dilute & concentrate urine
362
Primary tumors in the ureter are rare or common?
rare
363
What is the cellular origin of benign ureter tumors?
mesenchymal origin
364
What are 2 examples of benign primary tumors in the ureter?
Fibroepithelial polyps
| Leiomyoma
365
What are the malignant ureter tumors called?
transitional cell carcinoma (urothelial)
366
Name 2 other places transitional cell carcinoma (urothelial) can be found.
renal pelvis
| bladder
367
Malignant transitional cell carcinoma rarely appears alone in the ureter. Where do concurrent neoplasms usually exist?
bladder
renal calyx
(field effect)
368
What is the greatest risk factor for ureter cancer?
smoking
369
What are the odds that a smoker will get urothelial/transitional cell carcinoma?
~100% chance, 70s-80s
370
Is the ureter more like an artery or intestines?
the ureter is a muscular tube
| - active peristaltic contraction
371
What are the 3 cellular layers of the ureter?
- mucosa
- muscularis (smooth)
- adventitia
372
What kind of cells line the ureter?
transitional epithelium
373
What are intrinsic obstructive lesions of the ureter?
- calculi
- strictures
- neoplasms
- blood clots
- neurogenic bladder
- vesiculoureteral reflux
374
What are extrinsic obstructive lesions of the ureter?
- pregnancy
- preureteral inflammation
- sclerosing retroperitoneal fibrosis (Rx-induced)
- endometriosis
- neoplasm
375
What are the 4 types of cells in transitional epithelium?
Basal cells
Intermediate cells
Umbrella cells
basement membrane
376
What are the "replacement" cells in transitional epithelium?
Basal cells + intermediate cells
377
What do Umbrella cells do?
flatten with bladder filling, contract with emptying
378
What are 7 urinary bladder diseases?
- obstruction of bladder neck
- diverticula
- exstrophy
- urachus
- cystoceie
- vesicoureteral reflux
- neoplasm
379
What do you call a decrease in ureteral lumen?
stricture
380
What are 3 causes of ureteral strictures?
- congenital
- chronic inflammation
- retroperitoneal fibrosis
381
What can obstructive lesions of the bladder lead to?
Hydronephrosis
382
What is the mechanism of hydronephrosis?
obstruction >> increased pressure upwards toward kidney >> dilation of renal pelvis
383
If there is acute obstruction, why is there no change in BUN/creatinine?
obstruction causes increase pressure in medulla
| -- glomeruli are in the cortex
384
What are the lab values in hydronephrosis?
normal labs
385
What is neurogenic ureter?
interruption of neural pathways to the bladder
386
How does neurogenic ureter disrupt normal urine flow?
- loss of peristaltic function - easier back flow
| - lack of force propelling urine to bladder
387
What is the infection associated with virus-associated kidney disease?
Hep C
388
What is the Ig associated with virus-associated kidney disease?
RF: Ig that binds IgG (most commonly IgM)
389
What is the blood condition associated with virus-associated kidney disease?
cyoglobulinemia
390
What are the 3 types of complexes/deposits in virus-associated kidney disease?
- IgM RF (nephrotic)
- IgG binds HepC particle (nephrotic)
- IgM RF binds IgG bound to Hep C particle (larger complex too big >> nephritic)
391
What's the clinical presentation of virus-associated kidney disease?
- nephrotic + nephritic = mixed
- palpable purpura
- arthralgia
- asthenia (weak)
- organ involvement: renal + neuropathy
392
What's the morphology of virus-associated kidney disease?
- membranoproliferative glomerulonephritis
- expanded mesangium
- increased cellularity
- increase capillary thickness
- subendothelial deposits
393
What is the etiologies of Chronic TIN?
- NSAIDS, anti-inflammatory
- infection (vesicoureteral efflux)
- SLE/Sjogren's disease
- secondary to light chain, myeloma, amyloidosis, sarcoidosis
394
What is the progression of chronic TIN?
slow onset, gradual decrease in GFR + interstitial fibrosis
395
What are the morphological features of chronic TIN?
- large increase in interstitial fibrosis w/ few inflammatory cells
- decrease vascularity because decrease volume of capillaries
- tubular atrophy
- secondary glomerulosclerosis
396
What does the fibrosis lead to in chronic TIN?
increase fibrosis = decrease capillaries = decreased renal function
397
How is UTI and pyelonephritis related?
Bacterial infection in the urinary tract >> move up >> tubular interstitial nephritis
398
What are some common causes of UTI and Pyelonephritis?
- pregnancy (uterus pushes on bladder)
- instrumentation
- vesicoureteral reflux
- female shorter urethra
- diabetes mellitus
- immunodeficiency
399
What is the most common cause of UTI and Pyelonephritis?
- bacteria from rectum
400
What is a rare cause of UTI and Pyelonephritis?
hematogenous (from blood)
401
If left untreated, what are the complications of UTI and Pyelonephritis?
- pyonephrosis (pus in renal pelvis)
- perinephric abscess (infection spreads)
- scar formation (thyroidisation)
- acute papillary necrosis
402
Which bacteria are associated with UTI and Pyelonephritis, and why?
Ecoli, proteus, kelbesiela, enterocacter
| -- all depends on bacterial adhesion and migration
403
What is the clinical presentation of UTI and Pyelonephritis?
< 50 = females, short urethra
> 50 = males, BPH (decrease prostatic fluid)
- bladder is commonly infected (urethritis + cystitis)
- flank pain
- azotemia
404
Compare and contrast the clinical presentation of acute vs. chronic UTI and Pyelonephritis.
Acute: suppurative infllammation of pelvic/calyx + parenchyma
- Chronic: scarring, more associated w/ obstructive type; loss of nephrons
405
What is the macro profile of UTI and Pyelonephritis?
- swollen kidneys
- abscesses common
- U shaped scarrine
- hydronephrosis
406
What is the micro profile of UTI and Pyelonephritis?
- interstitial edema
- increased cells between tubules
- fibrous tissue and tubules
- granulomas
407
Name the 4 types of drugs that cause Drug-induced TIN.
- B-Lactams
- NSAIDSs/Analgesics
- Aminoglycosides
- Chinese herb
408
Name the 5 types of Drug-induced TIN.
- B-Lactams: Immunogenic interstitial nephritis from B-lactams (penicillin)
- NSAIDSs/Analgesics: prolonged administration >>phenacetic/acetaminophen toxicity
- Aminoglycosides: direct cytotoxic effect on IS (rifampin)
- Balken Endemic Nephropathy (slow) Aristolochic Acid toxicity
- Chinese Herb nephropathy: (FAST) Aristolochic Acid toxicity
409
Aristolochic Acid toxicity: Balken Endemic Nephropathy vs. Chinese Herb nephropathy. Fast or slow onset?
Balken - slow onset, slowly progressive
| Chinese - fast onset
410
Aristolochic Acid toxicity: Balken Endemic Nephropathy vs. Chinese Herb nephropathy. Which one is found in weight-reducing diets?
Chinese herb nephropathy
411
What are the renal complications associated with Balken Endemic Nephropathy (slow) Aristolochic Acid toxicity?
- renal tubular dysfunction >> ESKD
| - interstitial inflammation + carcinoma risk
412
What are the clinical manifestations of Aristolochic acid toxicity?
- mild proteinuria (< 1.0 g)
- hypertension
- gross hematuria (may be uroepithelial carcinoma)
- normal urine sediment
413
What causes the reaction in Immunogenic interstitial nephritis from B-lactams (penicillin)?
- not dose dependent
- Hapten-mediated
- neoantigen mediated
414
What is the clinical presentation of Immunogenic interstitial nephritis from B-lactams (penicillin)?
- fever, rash, +/- eosinophilia
- oliguric/non-oliguric renal failure
- UA: hematuria, pyruria, sub-nephrotic proteinuria, eosinophiluria
- enlarged kidney + interstitial inflammation
415
What is the micro profile of Immunogenic interstitial nephritis from B-lactams (penicillin)?
- Interstitial edema
- increased cells between tubules
- fibrous tissue and tubules
- granulomas
416
How does NSAIDSs/Analgesics: prolonged administration >>phenacetic/acetaminophen toxicity target the kidney?
- Drug accumulates and is highly concentrated in the renal medullary interstitium
417
What is the pathogenesis of NSAIDSs/Analgesics: prolonged administration >>phenacetic/acetaminophen toxicity?
NSAIDS >> direct cellular damage to endothelium
Analgesics >> tubular cell damage by oxidative stress
Both >> hypoxia >> lower PG >> increase metabolic need >> inflammation + hypoxia
418
What are the clinical presentation for NSAIDSs: prolonged administration >>phenacetic/acetaminophen toxicity?
NSAIDS:
- acute impairment of renal function
- non-nephrotic proteinuria or nephrotic range proteinuria
- hyperkalemia (tubular dysfunction)
- can become full nephrotic syndrome (resembles minimal change disease)
419
What are the manifestations of analgesic abuse?
- slow progressive impairment of renal function
- tubular dysfunction -- RTA, hyperkalemia
- nephrogenic diabetes
- papillary necrosis
- uro-epithelia cancer
420
What is the mechanism of Aminoglycosides: direct cytotoxic effect on IS (rifampin)?
direct tubular injury >> necrosis
421
What is the clinical presention of Aminoglycosides: direct cytotoxic effect on IS (rifampin)?
- increase serum creatinine
- hypokalemia (unique to this drug associated TIN)
- renal glucoria
422
Name 2 types of acquired cystic renal diseases.
- simple cyst
| - acquired cyst (chronic kidney disease)
423
What is the incidence of simple cysts and is it serious?
- common
| - no clinical consequence
424
How do you distinguish cancer from a simple cyst?
- radiographs
425
What are the radiographic features of a simple cyst?
- smooth contours
- avascular
- fluid signal (not solid tissue signal)
426
What is the etiology of acquired cysts of the kidney?
- acquired with chronic renal disease >> scarring of the kidneys
427
What do you call multiple acquired cysts in the kidney?
multicystic
428
multicystic vs. polycystic: distinguishes which origins?
- acquired vs. congenital
429
Name the disease and treatment asociated with acquired cysts.
- end stage renal disease (ESRD)
| - chronic dialysis
430
What are the imaging features of acquired cysts?
- hydronephrosis
| - shrunken end-stage looking kidney with multiple cysts
431
What is the chromosome affected in autosomal dominant polycystic kidney disease (ADPKD)?
ch. 16
432
What are the 2 ch. 16 mutations that cause autosomal dominant polycystic kidney disease (ADPKD)?
- Type 1 = polycystin 1 mutation
- Type 2 = polycystin 2 mutation
disease may follow the 2 hit hypothesis
433
Of Type 1 and Type 2 autosomal dominant polycystic kidney disease (ADPKD), which one is more common and which has an earlier presentation?
Type 1 is more common, & has an earlier presentation
434
What is the mechanism of autosomal dominant polycystic kidney disease (ADPKD)? What is the function of polycystin?
polycystin regulates tubular & vascular develpment in kidney, brain, lung, heart and pancreas
- after second hit, tubular cells proliferate as benign neoplasm and form their cyst
- worse w/ AVP (cAMP stimulation)
435
What is the incidence of autosomal dominant polycystic kidney disease (ADPKD)?
- most common form of PKD
- 1 in 800 = 500,000 cases
- 10% of dialysis its
- called Adult PKD b/c presents 30-40s
436
What is the presentation of autosomal dominant polycystic kidney disease (ADPKD)?
- hypertension, hematuria, flank pain, recurrent UTI
- also affects liver, pancreas, and intestine (compression/mutation)
- heart valve defect
- circle of willis aneurysms
437
What is the etiology of autosomal recessive polycystic kidney disease (ARPKD)?
PKHD1 gene mutation
438
What is the mechanism of autosomal recessive polycystic kidney disease (ARPKD)?
PKHD1 gene mutation >> dilation of tubules + proliferation >> dilation of tubules >> cyst formation
439
What is the epidemiology of autosomal recessive polycystic kidney disease (ARPKD)?
- BABIES die at birth due to giant kidneys compression of lungs
- 1/20,000
440
Name 3 types of congenital cystic renal diseases.
1. autosomal recessive polycystic kidney disease (ARPKD)
2. Medullary Cystic Disease
3. Nephronophthisis-Medullary Cystic Disease
441
What is the etiology of Medullary cystic disease?
- Type 1 = MCKD1 mutation
- Type 2 = MCKD2 mutation
Autosomal dominant
442
What is the mechanism of Medullary cystic disease?
cysts restricted to medulla
443
What is the presentation of Medullary cystic disease?
- salt wasting
- polyuria
- both types are milder than ADPKD
- seen in children
444
What is the etiology of Nephronophthisis-Medullary Cystic Disease?
- mutation in NPHP 1-5 genes
445
What does the NPHP 1-5 genes do?
- code for nephrocystins = proteins in epithelial cell cilia
446
What is the mechanism of Nephronophthisis-Medullary Cystic Disease?
mutated nephrocystins >> dysfunctional epithelial cell cilia >> ciliary dysfunction
447
What are the four groups/types of Nephronophthisis-Medullary Cystic Disease?
- infantile
- juvenile (most common)
- adolescent
- adult
448
What is the presentation of Nephronophthisis-Medullary Cystic Disease?
extra-renal manifestation
- retinitis pigmentosa
- interstitial fibrosis
- mental retardation
- cerebellar abnormalities
449
What is the histology of Nephronophthisis-Medullary Cystic Disease?
- small kidneys
- cysts at cortico-medullary junction
- TIN
- interstitial fibrosis
450
What are the 4 types/causes of secondary hypertension?
1. Aldosterone excess
2. Glucocorticoid excess/cushing's syndrome
3. Pseudohyperaldosteronism
4. Gordon's syndrome
451
What is the basic mechanism of aldosterone excess leading to secondary hypertension?
increase aldosterone >> increase Na retention >> increase vasoconstriction >> increase SNS activation >> increase BP
452
What is the detailed mechanism of aldosterone excess leading to secondary hypertension?
1. aldosterone acts on renal tubular collecting duct cell
2. increases ENaC translocation to luminal surface
3. increase Renin & aldosterone (exception)
4. high Na will increase lumen negative transepithelial charge >> low K+ retention >> increased hypokalemia
5. high K in lumen will provide substrate to alpha-intercalated K/H+ ATPase >> high H+ excretion >> metabolic alkalosis
453
What is the mechanism of glucocorticoid excess & Cushing's syndrome?
high glucocorticoids >> increase activation of aldosterone receptor >> high ENaC
454
What is the pathophysiology of glucocorticoid excess & Cushing's syndrome?
1. Enzyme 11-beta-hydroxy-dehydrogenase 2 exists to prevent glucocorticoids from binding to aldosterone receptors
2. In cases of excess glucocorticoids (Cushing's Syndrome), 11-BHD2 is overwhelmed
- low renin & aldosterone
- high Na will increase lumen negative transepithelial charge >> low K+ retention >> hypokalemia
- high K in lumen will provide substrate to alpha-intercalated K/H+ ATPase >> high H+ excretion >> metabolic alkalosis
455
What causes 11-beta hydroxy dehydrogenase 2 deficiency?
chronic licorice ingestion inhibits 11-BHD2
456
What is the mechanism of 11-beta hydroxy dehydrogenase 2 deficiency?
low 11-BHD2 >> high glucocorticoid activation of aldosterone receptor >> high ENaC >> high Na reabsorption
457
In 11-beta hydroxy dehydrogenase 2 deficiency, what is the status of:
- renin
- aldosterone
- Na+
- K+
- H+
- low renin and aldosterone
- high Na will increase lumen negative transepithelial charge >> low K+ retention >> high hypokalemia
- high K+ in lumen will provide substrate to alpha-intercalated K/H+ ATPase >> high H+ excretion >> metabolic alkalosis
458
What is the genetic mutation that causes Gordon's syndrome?
Mutation in WNK 4 (regulator of NCCT) or WNK1 (regulator of WNK 4) of NCCT
459
What is the mechanism of Gordon's Syndrome?
- high Na reabsorption in DCT
- This is proximal compared to other hyperkalemic diseases, which means you have less delivery of Na to the CD, so no extra excretion of K+
- hyperkalemia
460
What are the 3 types of acute kidney injury (AKI)?
1. Post-renal
2. Pre-renal
3. Intra-renal
461
What are 3 causes of Post-renal AKI?
Obstruction of urine flow
- prostate disease
- bilateral ureter occlusion from retroperitoneal malignancies
462
What is the presentation of Post-renal AKI?
- voiding complaints
| - PE shows distended bladder
463
What do the labs show in Post-renal AKI?
- normal urinalysis
| - diagnosed w/ ultrasound (look for dilated calyx)
464
What is the main problem in pre-renal AKI?
kidneys are normal, but not enough perfusion
465
What are the common causes of pre-renal AKI?
```
volume depletion
diuretics
3rd space (burns)
CHF
shock/sepsis
```
466
What lab values suggest a pre-renal cause of AKI?
- FeNa
- Urine Na
- Urine Osm
- FeNa < 1% = pre-renal
- Urine Na < 25 = body is compensating for decreased perfusion by inceased Na reabsorption
- Urine Osm > 500 = compensatory mechanism includes high AVD/ADH >> high urine osmolarity
467
What are 3 types/causes of pre-renal AKI?
- Hepatorenal syndrome
- Bilateral RAS w/ATII and ACE-I
- NSAID use
468
What condition most commonly leads to hepatorenal syndrome?
cirrhosis
469
What is the pathophysiology of hepatorenal syndrome?
Portal hypertension >> splanchnic vasodilation >> low ECFV >> increase RAAS >> high Na reabsorption + high renal vasoconstriction >> hepatorenal syndrome
470
What is the presentation of hepatorenal syndrome?
decreased BP despite increased extracellular fluid volume
471
What are the labs for hepatorenal syndrome?
- low urine sodium (<10)
- volume infusion trial to determine pre-renal
- rule out other causes (NSAIDS, contrast)
472
What is the basic mechanism of AKI in bilateral RAS w/ATII and ACE-I?
bilateral RAS >> no autoregulation >> collapse of GFR >> AKI
473
In bilateral RAS w/ATII and ACE-I, what is the relationship and function of:
- ACE
- ATII
- ACE-1
- ACE allows formation of ATII
- ATII >> vasoconstriction of efferent arteriole to maintain GFR >> autoregulation
- ACE-I inhibits autoregulation
474
What is the mechanism of AKI caused by NSAIDS?
- NSAID use >> inhibits autoregulation
| - NSAIDS >> COX inhibitor >> lowers PG production >> PG dilates afferent arteriole, so low RPF >> AKI
475
What is the presentation of NSAID induced AKI?
leads to AKI in patients with volume depletion, CHF, cirrhosis
476
What are the 3 types of intra-renal diseases leading to AKI?
- Acute tubular necrosis
- AKI from therapeutic agents
- Acute interstitial nephritis
477
What causes acute interstitial nephritis?
- allergic reaction to penicillins, cephalosporins, sulfonamides, NSAIDS
478
What is the presentation of acute interstitial nephritis?
fever, rash, joint pain, increased eosinophils on CBC
479
What does the urine labs show in acute interstitial nephritis?
pyuria +/- eosinophils + granulocytes
480
What are the 2 therapeutic agents that cause AKI in AKI from Therapeutic Agents?
- aminoglycosides
| - contrast agents
481
What is the mechanism of aminoglycosides causing AKI in AKI from Therapeutic Agents?
Aminoglycosides accumulate in proximal tubule cells and inhibit lysosomal function
482
What is the mechanism of Contrast agents causing AKI in AKI from Therapeutic Agents?
contrast nephropathy caused by contrast's direct vasoconstrictive effects and tubular toxicity
483
How do you prevent AKI from Therapeutic Agents?
- aminoglycosides: once daily dosing + monitor
- contrast: lower amount, avoid closely spaced studies, IV for volume depletion, acetylcysteine
- Both: avoid other nephrotoxins
484
What are the 2 main types of injury that cause acute tubular necrosis (ATN)?
Diffuse ischemia
| Toxic injury
485
What 2 main types of injury that causes diffuse ischemia leading to ATN?
- chronic pathological condition
- ---- leading to severe tubular damage and acute renal failure
- Ischemic injury
- ---- secondary to prolonged pre-renal disease (ischemia)
486
What are 5 examples of injury that causes diffuse ischemia in ATN?
- shock (septemia)
- hypotension (inadequate RPF)
- Hypovolemia
- severe burns
- pancreatitis
487
What are 8 causes of toxic injury in ATN?
- hemoglobinuria (hemolysis)
- myoglobinuria
- heavy metals: mercury, lead
- organic solvents: chloroform, ethylene glycol
- drugs: clyclosporine, antibiotics
- pesticides: paraquat, phenol
- fungal toxins
- contrast agents
488
Describe the different parts of the renal tubule affected by ischemia and toxic substances.
- ischemia affects short segments (ATP requiring)
| - Toxic substances affect long limbs
489
Is ATN reversible or irreversible, and why or how?
ATN is reversible with dialysis and supportive care
| - tubular cells will be replaced, but most will be immature and cannot function normally (polyuric)
490
What are the 3 phases of presentation of ATN?
```
Oliguric phase = severe tubular damage >> less reabsorption >> decreased GFR >> decreased urinary output (prevent hyperkalemia and fluid overload)
Polyuric Phase (1-3 wks later) = tubular cells are replaced w/ immature cells >> cannot reabsorb water >> hypotonic urine (give fluids)
Recovery Phase = tubular cells become differentiated; normal
```
491
What are the lab values of Urine Na and FeNa in ATN?
- urine Na > 20 -- intra-renal dysfunction
| - FeNa > 1%
492
What is the macro profile of ATN?
- pale and swollen kidneys
| - cortex is paler than medulla
493
What are the urinalysis results for ATN?
- muddy brown granular casts
- --- 100% indicative of intra-renal cause
- --- These are renal tubular epithelial cells that have sloughed off post-ischemic damage and combined with TH proteins >> casts
494
TIN vs ATN: what is the difference in urine casts?
- TIN = white blood cell casts
| - ATN = muddy brown casts
495
What is the treatment of ATN?
- restore perfusion
- avoid nephrotoxins (NSAIDS, contrast, ACE-I)
- Supportive care
496
How does PTH affect Ca levels? P levels?
PTH = increases Ca, decreases P
497
How does Calcitriol/Vit.D affect Ca levels? PTH levels?
increases Ca, decreases PTH
498
So how does P affect PTH levels?
high P >> inhibits calcitriol synthesis >> inhibiting the inhibitor of PTH >> high PTH
499
How does FGF-23 affect calcitriol/Vit.D levels?
FGF-23 increases P excretion >> lowers calcitriol/Vit.D synthesis
500
How does chronic kidney disease lead to secondary hyperparathyroidism?
In CKD, kidney or PTH cannot compensate for excess phosphate >> hyperphosphatemia >> increased PTH (secondary hyperparathyroidism)
501
How does increased PTH in CKD affect the bones and blood vessels?
- high PTH >> high bone turnover = osteogenesis
| - Calciphylaxis = calcification of blood vessels and/or ulceration
502
What is the treatment of Ca/P levels in CKD?
- Phosphate binders
- --- Ca based (carbonate, acetate; cause calcification
- --- Sevelamer HCL - great but pricey
- Lanthanum carbonate
- --- binds P as it is digested out of food
- --- 99.99% excretion
503
What are 3 types of benign renal tumors?
Renal adenoma
Angiomylolipoma
Oncocytoma
504
What are the major characteristics of a renal adenoma?
- is it benign or metastatic?
- what does the adenoma look like?
- low metastatic potential
- commonly associated with papillary structures
- finger-like projections with fibrous core
505
What is another name for angiomylolipoma?
benign harmatoma
506
Why are benign harmatomas called angiomyolipoma?
it is composed of smooth muscle, adipose tissue and vessels
- angio = vessels
- myo = muscle
- lipoma = fat
507
What are the major characteristics of benighn harmatomas (angiomyolipoma)?
- is it benign or metastatic?
- what does the harmatoma look like?
- nearly 100% benign
- can be pre or post-renal
- harmatoma: tissue growth of cells that are normally there, just disorganized
508
Where in the body are Oncocytomas found?
Benign tumor of kidney, thyroid, URI
509
What kind of cells are oncocytomas composed of?
large epithelial cells with abundant mitochondria
510
Is oncocytoma benign or malignant?
90% benign
- 3 histological grades
- grade III = malignant carcinoma
511
Name 5 malignant renal tumors
- Clear cell carcinoma
- chromophobe renal carcinoma
- papillary renal cell carcinoma
- Wilm's tumor (nephroblastoma)
- Transitional cell carcinoma
512
What is the basic cause of clear cell carcinoma?
Abnormal von Hippel-Lindau (VHL) gene
513
What are the genetic mutations associated with sporadic causes of clear cell carcinoma?
- del(3)
| - t(3;6), t(3;8), t(3;11)
514
Describe what happens to VHL in the hereditary form of clear cell carcinoma.
- loss of VHL
| - mutated + inactivated + methylated VHL
515
In the hereditary form of renal clear cell carcinoma, where are masses found?
familial cases have multiple masses bilaterally
516
How common is clear cell carcinoma?
- 80% of all renal cancers
| - 2% of all adult cancers
517
What is the prognosis of clear cell carcinoma?
- High mortality (hematuria seen too late)
| - not an aggressive cancer
518
What is the presentation of renal clear cell carcinoma?
```
60-70 y/o, smoking, obesity, HTN, high Ca, hematuria, flank pain
- May have paraneoplastic syndromes
Hypercalcemia
Hypertension
Polycythemia (EPO)
Cushing's syndrome (glucocorticoids)
```
519
What is the macroscopic profile of clear cell carcinoma?
necrosis
hemorrhage
pseudocapsule
520
What is the microscopic profile of clear cell carcinoma?
cells are not anaplastic
| Oil-red O stain reveals lipid vesicles
521
What is the etiology of Chromophobe Renal carcinoma?
Hypodiploidy - loss of multiple chromosomes
| - chromosomes lost: 1,2,6,10,13,17,21
522
How common is Chromophobe Renal carcinoma?
Rare (5% of all renal cancers)
523
What is the prognosis of Chromophobe Renal carcinoma?
it has a better prognosis than clear cell carcinoma
524
What is the histology of Chromophobe Renal carcinoma?
- cells have eosinophilic cytoplasm (not clear)
- variability in size
- cells have distinct membranes
525
What is the basic etiology of Papillary Renal Cell Carcinoma?
activated or mutated MET oncogene
526
What are the genetic mutations that cause sporadic Papillary Renal Cell Carcinoma?
- Trisomy 7, 16, 17 (mutated/activated MET)
- Loss of Y
- t(X;1) >> PRCC oncogenes
527
What is the genetic profile of Papillary Renal Cell Carcinoma?
- Trisomy 7
| - familial cases have multiple masses bilaterally
528
What is the prevalence of Papillary Renal Cell Carcinoma?
10-15% if all cancers
529
What is the presentation of Papillary Renal Cell Carcinoma?
hematuria
tobacco use
cystic renal disease
analgesic nephropathy
530
What is the macro characteristics of Papillary Renal Cell Carcinoma?
- pseudocapsule indicating slow growth
- Hemorrhage and necrosis
- --- these occur because tumor outgrows vascular size
531
What is the micro characteristics of Papillary Renal Cell Carcinoma?
- Finger-like projections w/ fibrous core
- fibrovascular core
- eosinophilic cytoplasm
- overlap with benign papillary tumors
- vimentin and cytokeritin +
532
What gene is mutated in Wilm's tumor (nephroblastoma)?
mutated WT1 (tumor suppressor gene - Ch.11)
533
How common is Wilm's tumor (nephroblastoma)?
3rd most common cancer in children
534
What is the prognosis of Wilm's tumor (nephroblastoma)?
90% cure rate with proper St. Jude therapy
535
What cell makes up Wilm's tumor (nephroblastoma)?
Arises from pluripotent metanephric cells
- kidney comes from mesenchymal cells
- many cell types are found in Wilm's tumor
536
What is the clinical presentation of Wilm's tumor (nephroblastoma)?
abdominal mass +/- hematuria, neonatal colic, < 4 yo
537
What is the macro profile of Wilm's tumor (nephroblastoma)?
typically large, round, fleshy white appearance
538
What is the micro profile of Wilm's tumor (nephroblastoma)?
many cell types b/c pluripotent origin
- primitive cells = metanephric blastema
- immature glomerular structures
- epithelial tubules
- spindle stromal/striated muscle
- +/- cartilage, osteoid, neural tissues, sq. epith.
539
Where in the urinary tract is transitional cell carcinoma found?
neoplasm of urothelium lining renal pelvis and lower tract
| - may spread down the urinary tract by seeding
540
How do stones/calculi affect transitional cells?
transitional cell >> squamous cell (metaplasia) in the presence of stones/calculi
541
What is the clinical presentation of Transitional cell carcinoma?
hematuria is seen early
| smokers
542
What is the mechanism of Acute TIN?
rapid onset; rapid decrease in GFR + interstitial edema >> decrease ccn of urine >> medullary/ papillary damage
543
What care the 2 types of injury in Acute TIN?
proximal tubule injury
| distal tubule injury
544
What are 3 causes of proximal tubule injury in acute TIN?
- antibiotics
- multiple myeloma
- analgesics/NSAIDs
545
What does Acute TIN cause in the proximal tubule?
decrease reabsorption of Na, AA, glucose, etc.
546
What are the 3 causes of Acute TIN affecting the distal tubule?
Antibiotics
immunologic disorders
analgesics/NSAIDs
547
What does Acute TIN cause in the distal tubule?
decrease reabsorption of Na
| decrease secretion of K+/H+
548
What are the morphological features of Acute TIN?
- increase interstitial volume from inflammatory mononuclear cell infiltration (lymphocytes, plasma, macrophages, +/- eosinophils)
- epithelial BM disrupted, epithelial cell necrosis
549
What are 4 important drugs/poisons to associate with Acute TIN and how would you detect each?
- Indinavir (anti-HIV) - calcium oxalate crystals
- Phenoytin - ppt in urine
- Rifampin - HPTN, flank pain
- Lead - anemia
