z-Renal Flashcards
1
Q
CA Inhibitor
A
Acetazolamide
2
Q
___ may be effective in patients w/ impaired renal function when class 1 thiazides are not
A
Metolazone, Indapamide (class 2 thiazides)
3
Q
2 main conditions that cause ADH release
A
Elevation in plasma osmolarity >280; Depletion of ECV
4
Q
2 Organic Base K-Sparing Diuretics
A
Triametrene, Amiloride
5
Q
2 Types of Na Channels in IMCD
A
(1) CNG: Amiloride-sensitive, cyclic nucleotide gated cation channel; (2) Low-conductance highly-selective Na ENaC channel
6
Q
3 Clinical uses of Osmotic Diuretics
A
Intra-cranial pressure, Intra-ocular pressure, Dialysis disequilibrium syndrome
7
Q
3 Drugs classes associated with SIADH
A
Psychotropics, Sulfonylureas, Vinca Alkyloids
8
Q
3 Net Effects of Loop Diuretics
A
(1) Significant NaCl loss; (2) Increase excretion of K, H; (3) Increase excretion of Ca, Mg
9
Q
4 Clinical uses of CA inhibitors
A
Cysteinurea, Intra-ocular pressure, Seizures, Mountain sickness
10
Q
4 Therapeutic Uses of Loop Diuretics
A
(1) Edema of cardiac, hepatic, or renal origin; (2) Pulmonary edema; (3) Hypercalcemia; (4) Protect against renal failure
11
Q
A poor response to Thiazides may reflect
A
Either an overwhelming load of dietary Na, or impairted renal capacity to excrete Na
12
Q
Action of ANP
A
Binds NP receptor-A, activates GC and increases cGMP
13
Q
Action of BNP
A
Binds NP receptor-A, activates GC and increases cGMP
14
Q
Action of CNP
A
Binds NPR-B in vascular SM cells –> Relaxation
15
Q
Action of Demeclocycline
A
Antagonizes ADH at V2R’s
16
Q
Activation of V1 receptor activates
A
Gq-PLC-IP3 pathway –> Mobilizes Ca –> Vasoconstriction
17
Q
Advantages of Torsemide
A
Also lowers BP; Longer Half Life
18
Q
Best tolerated drug classes for monotherapy in HTN
A
Diuretics, ACEi’s
19
Q
Bindin of ADH to V2 receptor activates
A
Gs-cAMP, PKA –> Insertion of AP-2, p-lation of urea transporter
20
Q
Bumetanide vs Furosemide
A
Bum is 40x more potent
21
Q
Class 2 Thiazides
A
Metolazone, Indapamide
22
Q
Clinical effects of Nesiritide
A
(1) Increase Na excretion; (2) Useful in CHF
23
Q
Clinical Uses of Spironolactone
A
Diuretic in combo with HCTZ; CHF, Cirrhosis
24
Q
Clinical Uses of Triametrene, Amiloride
A
Combined with HCTZ to decrease K excretion
25
Common preventable cause of diuretic resistance
Co-administration of NSAID with Loop
26
Concentration of urine in Mannitol use
Hypoosmotic (losing free water)
27
DDAVP is also used in
Bleeding disorders, Nocturnal Enurisis
28
Desmopressin
Highly selective V2R agonist
29
Difference between Loop and Osmotic
Loop have high [Na] in urine
30
Diuretic of choice in Cirrhosis
Spironolactone
31
Diuretic to use in Chronic Renal Failure
Loop
32
Diuretic to use in Mild CHF
Thiazide, Loop
33
Diuretic to use in Moderate or Severe CHF
Loop
34
Diuretic to use in Nephrotic Syndrome
Loop
35
Do PG's increase or decrease with Loop Diuretics?
Increase
36
Drug interactions of Furosemide
Li, Indomethacin, Probenecid, Warfarin
37
Effect of ADH on urea transport
V2 --> PKA p-lates urea transporter --> inc. permeability of CD to urea
38
Effect of Furosemide on K, H, Ca, Mg
Increases secretion of all
39
Effect of Furosemide on Renal PG's and Venous capacitance
Increases both
40
Effect of Osmotic Diuretics on PCT
Osmotically inhibit Na/H2O reabsorption
41
Effect of Thiazides on Ca, Mg
Decrease excretion of Ca, Increase secretion of Mg
42
Effect of Thiazides on Na, K, Cl
Loss of all three --> Hypokalemia
43
Effect of Triametrene, Amiloride on Na, K, H
Weak excretion of Na; Inhibit secretion of K, H
44
Eplerenone vs Spironolactone
Lower affinity for AR's so less side effects
45
Found in urine, paracrine regulator of Na transport
Urodilantin
46
Furosemide vs Indomethacin
NSAIDs inhibit PG effect of Furosemide
47
Furosemide vs Probenecid
Compete for secretion by Organic Acid Transporter
48
Furosemide vs Warfarin
Compete for protein binding
49
General MOA Acetazolamide
CA Inhibitor
50
General MOA Mannitol
Osmotic Diuretic
51
General MOA of AVP, DDVAP
V2R Agonism, Collecting Duct
52
General MOA of Conivaptan, Tolvaptan
V2R Antagonism, Collecting Duct
53
Given in large doses, Osmotic Diuretics
increase osmolarity of plasma
54
Highly selective V2R agonist
Desmopressin
55
How are Loop diuretics administered
IV in hypertensive crisis or in Acute Pulmonary Edema
56
How are Thiazides unlike Loops
Thiazides decrease secretion of Ca
57
How do Load-Dependent Principal cells work
The more Na is delivered, the more is absorbed in exchange for K secretion
58
How do Loop Diuretics affect Macula Densa
MD thinks very little Na, so it secretes PG's --> Increase RBF and FF
59
How do PG's affect actions of Loops
Reduce Na re-absorption in distal nephron, antagonize ADH, distribute renal blood from cortex to JG
60
How does Furosemide reach the luminal symporter
Secreted by Organic Acid Transporter
61
How does Furosemide travel in blood
Extensively protein bound
62
How does Hypovolemia lead to Hyponatremia
Hypovolemia stimulates ADH-mediate retention of H20
63
How does Nesiritide increase Na excretion
Inhibits CNG_nonspecific cation channel in IMCD; Inhibits RAAS
64
How will V2R agonist affect Central vs Nephrogenic DI
Increase urine osmolarity in central by not nephrogenic
65
In CHF, Cirrhosis, or Nephrotic Syndrome, hypovolemia is exacerbated by
Diuretics
66
In what condition is Mannitol contraindicated
CHF
67
Indications for Vaptans
Significant Hypervolemic and Euvolemic Hyponatremia (including patients with HF, Cirrhosis, SIADH)
68
Inhibiting CA results in loss of what in urine
Bicarbonate
69
K-Sparing Diuretics are useful in what patients
At risk of K depletion; Hyperuricemia
70
Late DCT, CD Principal cells are involved in __ re-absorption and __ secretion
Na reabsorption, K secretion
71
Like Loops, Thiazides require
secretion into tubular fluid to exert effect
72
Loop Diuretics
Furosemide, Bumetanide, Torsemide
73
Loop that also lowers BP
Torsemide
74
MOA of Loop Diuretics
Inhibit Na-K-2Cl symporter in TALH
75
MOA of Thiazide Diuretics
Inhibit NaCl reabsorption in the Na-K Aldosterone-independent sement of distal tubule
76
MOA of Triametrene, Amiloride
Inhibit Na re-absorption in late distal tubule (sodium load segment)
77
MOA of Vaptans
Selective V2R antagonists
78
Most popular drug for HTN
HCTZ
79
Most potent class of diuretics in mobilizing NaCl
Loop
80
Most Thiazides are ineffective when
GFR < 30-40 mL/minute
81
Net Effect of Aldosterone Antagonists
Increase excretion of Na; Inhibit secretion of K, H
82
Net effect of Osmotic Diuretics
Significantly increase urine
83
On which part of nephron do Triametrene, Amiloride act
Late Distal Tubule, Sodium Load segment
84
On which part of nephron does Furosemide act
TALH
85
Osmolarity of urine with ADH present
1200
86
Osmolarity of urine without ADH
50
87
Osmotic Diuretic
Mannitol
88
Patients with what type of HTN show better responses to Thiazides
Volume-dependent HTN (low renin)
89
Pharmacokinetics of Furosemide
Short half-life; Extensively protein-bound
90
Pharmacokinetics of Vaptans
CYP3
91
Physiological effects of Aldosterone
NaCl transport enhanced; Increased secretion of K, H+
92
Retention phenomena of Thiazides
Hyperuricemia, Hypercalcemia
93
Role of Renin in Loop Diuretic use
Potently increased
94
Route of Acetazolamide
Oral
95
Route of HCTZ
Oral
96
Route of Mannitol
Injection
97
Selective V2R antagonists
MOA of Vaptans
98
SIADH Tx:
Water restriction, Loops, Demeclocycline, Vaptans
99
Side effects of Acetazolamide
Metabolic Acidosis, K loss (hypokalemia)
100
Side effects of Furosemide
Hypokalemia, Ototoxicity; Elevated BUN, Hyperglycemia, Hyperuricemia
101
Side effects of Mannitol
Volume overload (don't use in CHF)
102
Side effects of Nesiritide are related to
its narrow therapeutic index
103
Side effects of Spironolactone
Hyperkalemia; AR: Gynecomastia, Hirsutism, Uterine Bleeding
104
Side effects of Triametrene, Amiloride
Hyperkalemia, Megaloblastic Anemia in cirrhosis
105
Side effects of Vaptans
Hyperglycemia, GI disturbances, Clotting probs
106
Sodium loss in Thiazides results in chronic
Reduced GFR
107
Spironolactone vs Canrenone
Sp is a pro-drug that is extensively metabolized; Can is active metabolite with longer half-life
108
T/F: Diuretics only reduce mortality from HTN when used with BB's
False, effective alone or in combo
109
T/F: Nesiritide reduces mortality in CHF
FALSE
110
Therapeutic Uses of Thiazides
Edema, Hypercalciurea, Essential HTN, Osteoporosis, Nephrogenic Diabetes Insipidus
111
Thiazides are widely used to treat
Mild or Moderate HTN
112
Tx of Central DI
Selective V2R agonists
113
Tx of Nephrogenic DI
Thiazide Diuretics
114
Type A Principal cells are regulated by
Hormone: Aldosterone
115
Type B Principal cells are regulated by
Load dependent
116
Type of channel in Aldosterone Sensitive Channel
Aldosterone-Sensitive ENaC Channel: Na-K/H
117
Type of channel in Na-K Aldosterone-independent segment
Na-Cl symporter
118
Type of Channel in Sodium Load Segment
ENaC Channel: Na-K/H
119
Type of channels affected by Aldosterone in DCT
Epithelial Sodium Channels (ENaC) are increased
120
Urine with Acetazolamide use
Alkaline, bicarbonate loss into it
121
Urodilatin arises from same precursor as
ANP
122
Use of Loop Diuretics for Non-Pulmonary edema
Oral use in Cardiac, Hepatic, or renal origin edema (GFR<30)
123
Uses of V1R agonists
Post-op Ileus; Esophageal varices; Acute Hem Gastritis
124
V2R agonism
Arginine Vasopressin, Desmopressin (DDAVP)
125
V2R Ant-agonism
Conivaptan, Tolvaptan
126
What causes acidosis with CA inhibitors
Enhanced chloride reabsorption
127
What is substituted for Furosemide in patients receiving Warfarin
Bumetanide
128
When are class 1 Thiazides perferably used
When GFR >50
129
When are class 2 Thiazides used
More potent, so when GFR<50 but greater than 30
130
When are K-Sparing Diuretics contraindicated
Significant Renal Insufficiency (GFR<75); Other K-retaining conditions
131
When are Loop used over Thiazides
Severe Htn unresponsive to Thiazides, especially w/ renal insufficiency, cardiac failure, cirrhosis
132
Where do CA inhibitors mostly act
Proximal Tubule (90%), Distal (10%)
133
Where do CNP's originate
Endothelium and Kidneys
134
Where do Loop Diuretics act
Inhibit Na-K-2Cl symporter in TALH
135
Where do Vasopressin and Desmopressin act
Collecting duct, V2R agoism
136
Where is V1 receptor found
Vascular SM
137
Where is V2 receptor found
Principal Cells in Renal CD
138
Which are more potent anti-hypertensives: Thiazides or K-Sparing
Equipotent
139
Which class of drugs creates largest volume of urine
Osmotic Diuretics
140
Which is preferred: Terlipressin or 8-arg vasopressin
Terlipressin has less side effects
141
Which parts of nephron have Aquaporin-1
Proximal Convoluted Tubule, Descending Limb
142
Which parts of nephron have Aquaporin-2
Collecting Duct
143
Why are Thiazides only mild diuretics
Act on distal tubule, which only absorbs 5% of Na
144
Why is Nesiritide useful in CHF
Decreases SVR, Decreases LVP, Increases CO
145
Wide margin of safety; Dose-response curve influence by renal disease
Furosemide
146
Glomerular diseases are often ___ mediated
Immunologically
147
___ injury may account for instances of GN in which either there are no deposits of Ab's or immune complexes
T Cell-Mediated injury
148
___ mechanisms underlie most types of primary glomerular diseases
Immune
149
___ molecules from adjancent foot processes bind to each other thru disulfide bridges
Nephrin
150
2 etiologies of Dense Deposit Disease
Auto-Ab to C3 Nephritic Factor - uncontrolled cleavage of C3; Mutations or Auto-Ab's to Factor H
151
2 most prevalent primary glomerular diseases in Adults
1. Focal Segmental Glomerulosclerosis; 2. Membranous Nephropathy
152
2 Typical Features of Immune Complex Disease
(1) Hypercomplementemia; (2) Granular deposits of IgG, complement on GBM
153
3 damaging substances released by Neutrophils
Proteases, ROS, AA metabolites
154
3 most frequent systemic causes of nephrOtic syn in adults are
Diabetes, Amyloidosis, SLE
155
5 manifestations of Nephritic Syndrome
Hyper GrAPE: HTN, Gross Hematuria, Azotemia, Proteinuria, Edema
156
85% of Membranous Nephropathy is caused by
Ab's that cross-react with podocyte antigens
157
AA metabolites released by Neutrophils cause
reduction in GFR
158
Ab-mediated GN in humans results from
Formation of auto-Ab's directed against GBM
159
Ab's against what are suspected when immune complexes are not found in GN
Against Glomerular cell antigens
160
Acute Postinfectious GN is caused by
Glomerular deposition of immune complexes; Results in proliferation and damage to glomerular cells and infiltration of leukocytes
161
After "maladaptive" changes following significant Nephron loss, what happens?
Capillary obliteration, Increased deposition of mesangial matrix and plasma proteins, and ultimately sclerosis of glomeruli --> Further reductions in nephron mass
162
After significant nephron loss, remaining glomeruli tend to undergo ___? This is associated with what hemodynamic changes?
Hypertrophy to maintain overall renal fxn; Increases single-nephron GFR, BF, and transcapillary pressure
163
Age range for IgA Nephropathy
Children and Young Adults
164
Age range for Minimal Change Disease
1-7 years
165
Age range of Membranous Nephropathy
30-60, slowly progressive
166
Alport Syndrome is a mutation in
Alpha chains of Type IV Collagen
167
Alport Syndrome is a type of
Hereditary Nephritis
168
Alport Syndrome is characterized by
Nephritis, Nerve Deafness, Eye disorders
169
Anti-GBM Ab GN is characterized by what IF pattern
Linear
170
Anti-GBM Ab-mediated Crescentic GN is characterized by
Linear deposits of Ig, and often C3 on GBM
171
Anti-GBM Crescentic: Clinical presentation
Severe glomerular damage with necrosis and crescents - Rapidly progressive GN
172
Antibodies directed to what glomerular region tend NOT to elicit inflammation
Subepithelial
173
Antigen in most cases of Membranoproliferative GN
Unknown
174
Antigens in Classic Crescentic GN
Fixed antigens in GBM
175
Auto-Ab to C3 Nephritic Factor - uncontrolled cleavage of C3; Mutations or Auto-Ab's to Factor H
2 etiologies of Dense Deposit Disease
176
Azotemia, Hematuria, HTN in NephrOtic syn
Little to no Azotemia, Hematuria, HTN
177
Basketweave =
Hereditary Nephritis
178
Best-characterized Anti-GBM GN
Classical Anti-GBM Crescentic GN
179
Causes of MPGN vs DDD
MPGN is immune complex deposition vs DDD is Complement dysregulation
180
Characteristic histological findings in RPGN
Crescents
181
Characteristic IF picture of IgA Nephropathy
Mesangial deposition of IgA (often with C3, properdin, and small amounts of IgG or IgM)
182
Chronic renal disease damages what components of nephron
All 4
183
Classic presentation of Acute Post-Strep GN
Nephritic Syndrome
184
Collapse of Glomerular Tuft and Podocyte Hyperplasia
Collapsing Gnephropathy is characterized by
185
Collapsing Gnephropathy is a variant of
FSGS
186
Collapsing Gnephropathy is characterized by
Collapse of Glomerular Tuft and Podocyte Hyperplasia
187
Complexes deposited in what location tend to elicit inflammatory reaction
Endothelium or subendothelium
188
Crescents can be a complication of any
immune complex nephritides
189
Cut-offs for Proteinuria and Hypoalbuminea in NephrOtic syndrome
3.5g proteinuria, 3 g/dL Albumin
190
DDD (as opposed to Type 1 MPGN) is characterized by
Ribbon-like intramembranous deposits
191
Deposition of Auto-Ab's directed against GBM show what pattern on IF
Linear pattern
192
Deposition of circulating immune compelxes gives what IF pattern
Granular
193
Diameter of Fenestra
70-100 nm
194
Diameter of Filtration Slits
20-30 nm
195
Early and Late EM changes in Hereditary nephritis
Early: Thin GBM; Late: Basketweave
196
Elevation of BUN and Creatinine; Usually reflects decreased GFR
Azotemia
197
EM findings in Post-infectious GN
Subepithelial Humps
198
Evidence suggests that IgA Nephropathy is an abnormality in
IgA production and clearance; Ab's against abnormally glycated IgA
199
FSGS is associated with what other conditions
HIV, Heroin abuse; Secondary event in other forms of GN
200
Fundamental Abnormality in Dense Deposit Disease
Excessive complement activation
201
Glomerular lesions from immune complex disease usually consist of
Leukocyte infiltration into glomeruli; Variable proliferation of endothelial, mesangial, and parietal epithelial cells
202
Gross Hematuria, Proteinuira, Azotemia, Edema, HTN: Hyper GrAPE
Nephritic Syndrome
203
Hallmark of IgA Nephropathy
Deposition of IgA in Mesangium
204
Hemodynamic changes caused by Hypertrophy of remaining nephrons in end-stage kidney disease lead to
Further endothelial and podocyte injury, increased glomerular permeability to proteins, accumulation of proteins and lipids in mesangial matrix
205
Hereditary Nephritis is caused by
Mutations in genes encoding GBM proteins
206
Histologic features of glomeruli in FSGS
Increased MM, Obliterated capillary lumina, Deposition of hyaline masses and lipid droplets
207
Histological features shared by Type 1 MPGN and DDD
Lobular G, Proliferation of Mesangial and Endothelial cells, Thickened GBM, Tram Track
208
How do immune complexes mainly produce injury in Glomerulus
Activation of complement and recruitment of leukocytes
209
How does Membranous Nephropathy contrast to Minimal Change disease
No selectivity of proteins, No response to corticosteroids
210
How does Thromin contribute to GN
Causes leukocyte infiltration and Glomular Cell proliferation by triggering PAR's (protease-activated receptors)
211
IF findings in Post-infectious GN
Granular deposits of IgG and Complement
212
IF showing deposition principally in mesangial regions
IgA Nephropathy
213
IgA Nephropathy is often considered a local variant of
Henoch-Schonlein Purpura
214
Inheritance of Hereditary Nephritis
Most commonly X-linked
215
Interestitial diseases are more likely caused by
Toxic or infectious agents
216
Irregular foci of thickening or attenuation with pronounced splitting and lamination of lamina densa
What is basketweave appearance
217
Kidney sin Anti-GBM Ab-mediated Crescentic GN
Enlarged and pale with Petechiae
218
LM of Glomeruli in Hereditary Nephritis
Normal until late in disease course
219
Lobular G, Proliferation of Mesangial and Endothelial cells, Thickened/Split GBM (tram track)
Histological features shared by Type 1 MPGN and DDD
220
Main histologic feature of Membranous Nephropathy
Diffuse thickening of capillary wall
221
Manifestation of Hereditary Nephritis
Hematuria and slowly progressing proteinuria and declining renal function
222
Manifestation of Minimal Change Disease
Insidious nephrotic syndrome in otherwise healthy child
223
Manifestation of Rapidly Progressive GN
ProMD: Proteinuria, Microscopic Hematuria, Dysmorphic RBCS, Casts
224
Manifestations of Nephrotic besides Proteinuria, Hypoalbumin, Edema
Hyperlipidemia, Lipiduria
225
Membranous Nephropathy is a form of
Chronic Immune Complex Glomerulonephritis
226
Membranous Nephropathy is characterized by
Subepithelial Ig deposits along GBM
227
Most cases of RPGN are ___ mediated
Immune
228
Most characteristic LM change in Post-infectous GN is
Increased cellularity of tufts in nearly all glomeruli
229
Most common cause of Nephritic Syndrome worldwide
IgA Nephropathy
230
Most common glomerular disease revealed by renal bx worldwide
IgA Nephropathy
231
Most important of the primary glomerular lesions that characteristically lead to nephrotic syndrome
Focal and Segmental Glomerulosclerosis (Adults); Minimal Change Disease (Children)
232
Most planted antigens induce what pattern in IF microscopy
Granular pattern
233
Nephritic syndrome lesions are characterized by
Proliferative changes and Leukocyte infiltration
234
Nephrolithiasis is manifested by
Renal colic, hematuria, Recurrent stones
235
Normal appearance by LM, but diffuse effacement of foot process by EM
Minimal Change Disease
236
Oliguria or Anuria + Recent Onset Azotemia
Acute Kidney Injury
237
Once in end-stage renal disease, kidneys show widespread
Glomerusclerosis
238
Only visible glomerular abnormality in Minimal Change Disease
Uniform and difuse effacement of foot processes of podocytes
239
Onset of IgA Nephropathy
Episode of gross hematuria that occurs within 1-2 days of nonspecific URI
240
Onset of Post-infectious GN
Abrupt
241
Pattern of deposits on IF in Membranous Nephropathy
Granular
242
Podocytes in EM of FSGS
Effacement of Foot Processes
243
Postrenal Azotemia
When urine flow is obstructed below level of kidney
244
Prerenal Azotemia
Hypoperfusion of Kidneys; Decreases GFR in absence of parenchymal damage
245
Presentation/Age of Hereditary Nephritis
Hematuria/Proteinuria at 5-20 years; Renal failure at 20-50 years
246
Primary FSGS accounts for what percent of nephrOtic syn
20-30%
247
Probably cause of HTN in Nephritic syn
Fluid Retention and Increased Renin
248
Prognosis of Acute Post-Infectious GN in children vs adults
Most children recover; worse in adults
249
Prognosis of DDD
Poor, worse than Type 1 MPGN
250
Prognosis of FSGS
Poor, 50% develop end-stage kidney disease in 10 years
251
Prognosis of Minimal Change Disease
Good, more than 90% of children respond to short course corticosteroids
252
Prognosis of Type 1 MPGN
Poor
253
Progression of FSGS leads to what histological picture
Global Sclerosis, Pronounced Tubular Atrophy, Interstitial Fibrosis
254
Proteinuria, Microscopic Hematuria, Dysmorphic RBCS, Casts
Manifestation of Rapidly Progressive GN
255
Puzzling aspect of Membranous Nephropathy
Immune complexes cause capillary damage in absence of inflammatory cells (likely via complement instead)
256
RAAS in Nephrotic Syndrome
Activated due to decreased intravascular volume
257
Renal colic, hematuria, Recurrent stones
Nephrolithiasis is manifested by
258
Renal function in Minimal Change Disease
preserved in most children
259
RPGN is characterized by
Progressive loss of renal function, Lab findings of Nephritic Syndrome, often severe oliguria
260
Segmental distribution of necrotizing and crescentic GN is typical of
ANCA-associated crescentic GN
261
Spike and Dome =
Membranous Nephropathy
262
Subepithelial Humps =
Post-infectious GN
263
The classic case of poststrep GN develops in
a child 1-4 weeks after GAS infection
264
The major component of slit diaphragms
Nephrin
265
Timeline of Rapidly Progressive Glomerulonephritis
Fews days or weeks
266
Tissue injury in Post-Strep GN is primarily caused by
complement activation by the classical pathway
267
Tram Track =
MPGN
268
Tubular diseases are more likely caused by
Toxic or infectious agents
269
Two possible causes of Membranoproliferative GN
Circulating immune complexes, or planted antigen the in situ complex formation
270
Tx of Anti-GBM Ab-mediated Crescentic GN
Plasmapharesis
271
Tx of Minimal Change Disease
Corticosteroids
272
Type 1 MPGN (as opposed to DDD) is characterized by
Discrete subendothelial electron-dense deposits
273
Type of Collagen in GBM
Type IV
274
Types of "planted" antigens
Nucleosomal complexes, Bacterial products, Large aggregated proteins, Immune complexes
275
Uremia
When Azotemia gives rise to clinical manifestations and systemic biochemical abnormalities
276
Urine in Post-Infectious GN
Gross Hematuria (smoky brown), Some proteinuria
277
Visceral Epithelial Cells =
Podocytes
278
Well-develped Membranous Nephrophy shows
Diffuse thickening of capillary wall
279
What can reverse podocyte changes in Minimal Change Disease
Corticosteroids
280
What causes 65% of primary glomerual disease in children?
Minimal Change Disease
281
What causes the "splitting of the GBM" (tram track)?
Extension of processes of mesangial and inflammatory cells into peripheral capillary loops and deposition of mesangial matrix
282
What conformational change appears to be key to auto-Ab attack of GBM
Alpha3 subtupe of Type IV collagen
283
What does Azotemia usually reflect
Decreased GFR
284
What endogenous podocyte antigen is most recognized by causative Auto-Ab's in Membranous Nephropathy?
PLA2 receptor
285
What forms crescents in RPGN
Proliferation of Parietal Cells and Migration of Monocytes/Macrophages in Bowman's space
286
What is Azotemia?
Elevation of BUN and Creatinine; Usually reflects decreased GFR
287
What is basketweave appearance
Irregular foci of thickening or attenuation with pronounced splitting and lamination of lamina densa
288
What is more pronounced in RPGN than in Nephritic Syndrome
Oliguria and Azotemia
289
What is the Tram Track
Thickened GBM with double contour glomerular capillary wall in MPGN
290
What is thought to cause injury in neutrophil-independent GN
Complement, MAC
291
What is thought to represent initiating event in FSGS?
Injury to podocytes
292
What likely damages mesangial cells and podocytes in Membranous Nephropathy
MAC activated by Immune Complexes
293
What mutation seems to be strongly associated with increased risk of FSGS and renal fialure in AA's
APOL1
294
What percent of GFR is reduced before inexorable progression to end-stage kidney disease
30-50%
295
What predicts progression and response to intervention in IgA Nephropathy?
Bx
296
When anti-GBM Ab's cross react with BM of lungs
Goodpasture Syndrome
297
When Azotemia gives rise to clinical manifestations and systemic biochemical abnormalities
Uremia
298
Which are permeable in glomerulus: cations or anions?
Cations - More cationic, more permeable
299
Which RPGN subtype shows segmental necrosis?
All 3
300
What does Trichrome stain highlight
Collagen
301
What is becoming the most common type of Crescentic Glomerulonephritis
Pauci-immune
302
In situ immune complex formation with Ab's against podocyte cell membrane antigens causes great majority of
Membranous Glomerulonephritis
303
What does Global Glomerular Disease refer to
Involves all of a single glomerulus
304
What does Diffuse Mesangial Sclerosis mean
Sclerosis of all the mesangium in one glomerulus
305
Location of immune complex deposition in Post-Strep Glomerulonephritis
Subepithelial
306
What causes Crescentic Glomerulonephritis
Leakage of Plasma Proteins into urinary space (particularly when mixed with Ab's, Immune Complexes, Inflammatory Cytokines, Inflammaotry cells, and ROS)
307
Important Concept: ____ is a major mechanisms of glomerular injury
Antibody deposition
308
Mutations in what result in congenital nephrotic syndromes?
Nephrin and Podocin
309
Urine in Malignant HTN
Marked Proteinuria, Microscopic Hematuria
310
Features of Perlecan
Strong negative charge - prevents Albumin from entering
311
What activates the Complement pathway in IgA Nephropathy
Mesangial cells are activated in response to binding and phagocytosing immune complexes --> Proliferate and increase production of ECM proteins and cytokines
312
Features of Laminin
Binds to other components
313
Subepithelial Humps
Pattern of immune complex deposits in Post-Strep Glomerulonephritis EM
314
Leukocyte mechanisms of glomerular injury and malfunction
Leakage of lysosomal proteases and ROS, Production of AA metabolites that reduce GFR
315
Form of Glomerulonephritis w/ localization of immune complexes in the mesangium
IgA Nephropathy
316
What is the Non-Collagenous Domain
Non-helical globular domain
317
Features of Entactin
Calcium binding properties
318
Infectious diseases involve what parts of nephron
Tubules and Interstitium far more often than glomeruli
319
What mediates the accelerated aging in DM
Advanced Glycation end-products (AGE)
320
What is Arterio-Nephro-Sclerosis
(1) Narrowing of lumen from plasma leakage; (2) Gradual ischemic atrophy of glomerulus; (3) End result is global sclerosis of glomeruli
321
Result of Foot Process Effacement
Retraction and loss of SPD; Detachment from GBM and degradation of GBM --> Plasma protein linkage
322
In whom is malignant HTN more common
Black males around 40
323
What tends to have a Linear pattern on immunofluorescence and be invisible on EM
Anti-GBM Ab deposition
324
What are Thrombotic Microangiopathies
Loss of normal endothelial function needed to prevent thrombosis
325
2 diseases associated leading to Arterionephrosclerosis
HTN, DM
326
Wire Loops
Extensive confluent subendothelial deposits thickening the capillary walls
327
Crescent Glomerulonephritis is associated with
Rapid Progression of Disease
328
Nephrin and its associated protein are crucial to
Maintaining selective permeability of glomerular filtration barrier
329
What happens to GBM in DM
Glycosylated plasma proteins get trapped --> GBM gets thickened
330
Crescent-shaped area of inflammation w/ proliferation of parietal epithelial cells
Crescentic Glomerulonephritis
331
2 diseases associated with ApoL1 mutation
Arterionephrosclerosis, Focal Segmental Glomerulosclerosis
332
Strong negative charge - prevents Albumin from entering
Features of Perlecan
333
Gross appearance of kidney in malignant HTN
Flea-Bitten
334
What happens to arterioles in Malignant HTN
Fibrinoid Necrosis of Arterioles
335
What is Crescentic Glomerulonephritis
Crescent-shaped area of inflammation w/ proliferation of parietal epithelial cells
336
Diseases caused by Ab's against epitope in the NC1 domain of alpha3 chain cause
Glomerulonephritis w/ Hematuria
337
Effects if DM on nephron
Mesangial cell hypertrophy and hyperplasia; Diffuse mesangial matrix production; Podocyte injury and apoptosis; Thickening of tubular BM's
338
Most common glomerular disease
Vascular, Hypertensive Nephropathy
339
What causes the damage in IgA Nephropathy
Complement activation generates the injurious inflammation
340
Feedback loop with hypertensive kidney disease
Glomerular Disease causes HTN, and HTN causes glomerular disease
341
In whom is end-stage renal disease due to HTN more common
8x more common in blacks
342
What can cause Crescentic Glomerulonephritis
Leakage of plasma proteins into urinary space (particularly when mixed with Ab's, Immune Complexes, Inflammatory Cells, and ROS)
343
Renal neoplasms arise from
Tubular Epithelium
344
Calcium binding properties
Features of Entactin
345
Result of injury to glomerular capillary endothelium
Loss of normal endothelial function needed to prevent thrombosis
346
Pattern of immune complex deposition in immunofluorescence
Clumps, granular pattern
347
What does PAS stain highlight
Cellular cytoplasmic inclusions
348
Goodpasture Syndrome
Glomerulonephritis w Hematuria, along w/ Pulmonary Hemorrhage and Hemoptysis
349
Effect of supra-normal glomerular capillary pressure on glomerulus
GBM thickening, Mesangial Hypertrophy and Hyperplasia, Mesangial Matrix production
350
Platelet mechanisms of glomerular injury in immune-mediated disease
Release AA metabolites
351
When proliferating parietal epithelial cells and infiltrating macrophages and inflammatory exudate and leaked plasma create a visible crescent of inflammation around glomerular tuft of cpaillaries
Crescentic Glomerulonephritis
352
Most common cause of glomerular disease
Hypertension
353
Slit Pore Diaphragm proteins that serve to bind adjacent pediceles
Cadherin, FAT
354
3 most common types of glomerular disease
(1) HTN, (2) Diabetic, (3) Immune-mediated
355
Glomerular diseases that involve the capillary endothelium or subendotheial portion of glomeruli tend to cause
Hematuria
356
Site of Ab deposition in SLE
Subendothelial
357
Compensation for nephron loss requires
Increased filtration per glomerulus and increased glomerular transcapillary pressure
358
In conditions causing severe loss of protein thru slit pore diaphragms, EM frequently shows
Fusion of Foot Processes = Effacement
359
What stain highlights the GBM
Jones silver stain
360
Ab against NC1 domain + Ab's against lung basement membrane
Goodpasture Syndrome
361
Second most common glomerular disease
DM
362
Mesenchymal cells w/ phagocytic and contractile properites
Mesangial Cells
363
With what is C-ANCA associated
Granulomatosis with Polyangiitis
364
Anti-GBM Ab deposition tends to have what pattern
Linear pattern on immunofluorescence and be invisible on EM
365
Vascular clotting disorders such as HUS, TTP, and DIC involve what part of nephron
Glomerulus
366
End result of many glomerular diseases
Fibrous replacement of glomerulus = Glomerulosclerosis
367
IgA Nephropathy is due to
Production of Abnormal IgA that self-aggregates and binds IgG --> immune complex formation --> Mesangial cell activation --> Complement-mediated injurious inflammation
368
What is hypothesized to happen in Post-Strep Glomerulonephritis
Antigens and Ab's arrive in glomerulus separately and form complexes in situ
369
Features of Fibronectin
Connection and adhesion of components
370
Extensive confluent subendothelial deposits thickening the capillary walls
Wire Loops
371
Connection and adhesion of components
Fibronectin
372
Glomerular diseases that involve which side of glomerulus are worse
Capillary side
373
Treatment of Anti-GBM Ab disease
Removing them with Plasmapharesis
374
What causes the great majority of Membranous Glomerulonephritis
In situ immune complex formation with Ab's against podocyte cell membrane antigens
375
Glomerular diseases that involve only the podocytes, slit diaphragm, or subepithelial portion of the glomeruli tend to cause
Proteinuria
376
Location of In situ immune complex formation and deposition
Subepithelial
377
Presentation of Malignant HTN
Symptoms of increased intracranial pressure: Headache, Scotomas, Vomitting
378
Anti-GBM disease is associated with
Smoking, being male
379
What happens to surviving nephrons after nephron loss
Hypertrophy, with hyperplasia of glomerular and tubular cells, longer tubules
380
Hyperplastic Arteriosclerosis + Arterial Fibrinoid Necrosis
Malignant HTN
381
What causes Flea-Bitten Kidney
Small arteries/arterioles damaged by malignant HTN rupture all over kidney
382
Toxic diseases tend to involve what part of nephron
Tubules more than Glomeruli
383
Hyaline Sclerosis in HTN vs DM
In HTN, just afferent arteriole; In DM, both
384
(1) Narrowing of lumen from plasma leakage; (2) Gradual ischemic atrophy of glomerulus; (3) End result is global sclerosis of glomeruli
What is Arterio-Nephro-Sclerosis
385
Glomerulonephritis w Hematuria, along w/ Pulmonary Hemorrhage and Hemoptysis
Goodpasture Syndrome
386
Histopathologic correlate of the clinical syndrome of rapidly progressive glomerulonephritis
Crescentic Glomerulonephritis
387
What does Segmental Glomerular Disease mean
Involves only part of glomerulus
388
Membranous glomerulopathy is characterized by
Increased glomerular basement membrane, w/out an increase in cells
389
What percent of glomerular disease in children is primary? In adults?
95%; 60%
390
With what is P-ANCA associated
Microscopic Polyangiitis, Churg-Strauss
391
Cell binding of basement membrane is mediated mostly by
Integrins
392
Slit Pore Diaphragm proteins that play role in filtration
Nephrin, Podocin
393
Effect of AA metabolites on glomerulus
Reduce GFR
394
AI diseases highly favor what part of nephron
Glomeruli
395
Formula for Plasma Osmolarity
(2 x Na mM) + (Glucose mOsm) + (Urea mOsm)
396
Major cation in ICF
K+
397
What happens to normal RBC when placed in solution of Low Pna and High Glycerol
Initially shrinks, then swells
398
Probes for Total Body Water
2H2O, 3H2O, Antipyrene
399
Formula for BV
BV= PV/(1-Hct)
400
Probe for measuring ECFV
Inulin, Thiosulfate, Na+
401
Is Cl- greater in plasma or interstitial fluid
Greater in interstitial fluid (Gibbs Donnan Effect)
402
Major cation in ECF
Na+
403
Is PO4+ greater in ICV or ECV
ICV
404
How does Infusion of Isotonic Salt Solution change ECF and ICF
Increase ECF, no change in ICF
405
Formula for ICF
ICF = TBW - ECF
406
Permeability of Na, Urea, Water, Glycerol across PM
Im, Per, Per, Slowly permeable
407
Is SO4+ greater in ICV or ECV
ICV
408
What causes Gibbs Donnan Effect?
Proteins impermeable to PM - Anionic so bind Na in plasma and repel Cl- into interstitial fluid
409
Is HCO3- greater in ICV or ECV
ECV
410
How do you correct for filtration/excretion in calculating ECF
Subtract excreted value from numerator
411
Ca2+ in ICF vs ECF
None in ICF
412
Is Na greater in plasma or interstitial fluid
Plasma (Gibbs Donnan Effect)
413
Formula for ISF (interstitial)
ISF = ECF - PV
414
Is Cl greater in ICV or ECV
ECV
415
If probe is metabolized, will it over or underestimate the volume
Overestimate
416
What percent of Blood is plasma vs rbc
60% plasma, 40% rbc
417
What to look for when elevated Osmolarity Gap
Missing Osmotic particle
418
2 Major anions in ECF
Cl-, HCO3
419
3 Major anions in ICF
Protein, Bicarb, Phosphate
420
Major extracellular anion
Cl-
421
If probe is synthesized, will it overestimate or underestimate volume?
Underestimate
422
What Osmolarity gap is abnormal
>10
423
What percent of water intake is from food + drink
88%
424
Is Mg greater in ICV or ECV
ICV
425
What percent of TBW is BV
8%
426
Formula for PV with probe
PV = Q / Conc.
427
Why is Inulin good probe for ECFV
Smaller than Albumin, can diffuse across capilary wall but not PM
428
Probe for measuring PV
131 I-Albumin, Evans blue dye
429
Uin =
GFR x Pin / UF
430
What is extraction ratio
Percentage of substance removed from plasma
431
How does Pcr change after Uninephrectomy
If GFR decreases by half, Pcr doubles
432
If substance is reabsorbed it means what for Clearance
Clearance less than GFR
433
Filtration Rate =
GFR x Px
434
GFR =
Uf x Uin / Pin
435
Mass Flow =
Concentration x Volume Flow
436
If substance X is completely cleared from plasma, Cx =
Total Renal Plasma Flow
437
How does Plasma Creatinine relate to GFR
Logarithmic, Creatinine not very sensitive = takes a large decrease in GFR to get significant increase in Pcreatinine
438
Rate of Output from kidney depends on
Renal Vein + Lymphatics + Urine
439
If substance is secreted it means what for Ex Ratio
Higher
440
Clearance of what substance approximately equals Effective Renal Plasma Flow
PAH
441
If substance is secreted it means what for Clearance
Clearance is greater than GFR
442
Clearance of Inulin essentially =
GFR
443
Cin =
(UF x Uin) / Pin
444
How does Clearance of Creatinine compare to Inulin
A little higher b/c creatinine is secreted
445
Rate of Filtration or Excretion =
Solute Conc. x Volume Flow Rate
446
Extraction Ratio =
(Ax-Vx)/Ax
447
If substance is reabsorbed it means what for Ex Ratio
Lower
448
Excretion Rate =
UF x Ux
449
Water input to kidney is same as
Plasma flow into kidney
450
Cpah =
Effective Renal Plasma Flow
451
Extraction ratio of PAH
0.9 - 0.95
452
How does Ang 2 affect renal arteriolar resistance and GFR
Induces renal arteriolar constriction and reduces GFR, paradoxically opposing auto regulation
453
How does Sympathetic affect Kf
Decrease Kf by stimulating mesangial cells -> Dec GFR
454
Proteinuria can either be from barrier failure or ___
Abnormal Circulating Protein (breakdown of tissue, production of abnormal proteins)
455
How does dec Cl in DT affect Renin
Inc Renin -> Inc Ang II, etc
456
Net Filtration Pressure =
(Pg + Pibs) - (Pig + Pbs)
457
Higher NaCl at MD =
Inc Afferent Arteriolar R -> Dec GFR
458
When is Autoregulation more important vs Sympathetics
Autoregulation dominates under normal conditions; Sympathetics only under severe ECFV loss
459
How does Endothelin affect GFR
Constrict Arterioles (aff and eff) -> Dec GFR
460
How do sympathetics control renin
B1 receptors stimulate renin in JG cells
461
Mechanism of GFR Autoreg: Dec GFR ->
Dec Cl in distal tubule -> MD -> Dec Arteriolar Resistance -> Inc GFR
462
2 locations where hydrostatic pressure drops
Afferent Arteriole; Efferent Arteriole/Peritubular Capillary
463
Kf =
Filtration Coefficient = Hydraulic Conductivity x SA of Glomerular Capillaries
464
How does Uretral Obstruction affect GFR, FF?
Reduce GFR and thus FF
465
T/F: Autoregulation in kidney depends on sympathetic input?
False, isolated in kidney
466
How does Low Capillary Flow affect FF, Pig, Net filtration pressure, GFR
Inc FF -> Inc Pig -> Dec Net Filtration Press -> Dec GFR
467
GFR =
Kf x Net filtration pressure
468
Lower NaCl at MD =
Dec Afferent Arteriolar R -> Inc GFR
469
Two Theories of Autoregulation
Myogenic, Tubuloglomerular Feedback
470
Adrenaline vs Endothelin 1 on resistance
Adrenaline is perferentially for Afferent, Endothelin does both
471
How does decreased efferent resistance affect GFR, RPF
Decreased GFR, Increased RPF
472
How does Adrenaline affect GFR
Constrict Arterioles (preferentially afferent) -> Dec GFR
473
Size of Albumin
6nm or 60 angstroms
474
Normal GFR is __ mL/min, ___ L/day
130 mL/min; 180 L/day
475
How does increased efferent resistance affect GFR, RPF?
Increase GFR, Decrease RPF
476
Hydraulic Conductivity x SA of Glomerular Capillaries
Kf (Filtration Coefficienty)
477
How does Renal Artery Stenosis affect RPF, FF?
Reduces RPF, thus increases FF
478
Anions and Cations in Glomerulus vs Ultrafiltrate
4-5% more anions in ultrafiltrate and 4-5% less cations - Gibbs Donnan effect
479
What is the filtration fraction?
GFR / RPF
480
Size of glomerular pores
8nm or 80 angstroms
481
How does decreased Afferent resistance affect GFR, RPF
Increase GFR, RPF
482
How does DM affect GFR
Decreases Kf, so decreases GFR
483
How does increase Afferent resistance affect GFR, RPF?
Decrease GFR, RPF
484
When does sympathetic response act on nephron?
Overrides autoregulation in severe ECFV loss
485
How does sympathetic activation affect Resistance, RPF, GFR
Constriction of Aff and Eff -> Dec RPF and Pg -> Dec GFR
486
What does the Tubuloglomerular feedback mechanism sense
NaCl at Macula Densa
487
Alternate route that Inc GFR -> Inc Arterolar R
Inc GFR -> Inc Cl in DT -> Na-K-Cl in MD cells -> Release ATP or AA metabs -> SM contraction -> Inc Art R
488
How does NO affect GFR?
Decreased Vascular R -> Inc GFR
489
How does pressure affect renin release
Increased pressure in afferent arteriole inhibits renin release from JG cells; Vice versa
490
What effect on net filtration pressure does lower urinary tract obstruction have?
Increase Pbs --> Decrease GFR
491
How do PG's affect GFR?
Decreased Vascular R -> Inc GFR
492
The kidneys receive what percent of cardiac output?
20%
493
Source of Endothelin that affects GFR?
Damaged endothelial cells
494
Mechanism of GFR Autoreg: Inc GFR ->
Inc Cl in distal tubule -> MD -> Inc Arteriolar Resistance -> Dec GFR
495
Symptoms of Glucosuria
Thirst and Nocturia due to Osmotic Diuresis
496
Phosphate Reabsorption is coupled to what in PT
Na
497
What facilitates water reabsorption in PT
Leaky epithelium and High Hydraulic conductivity
498
What drives active transport of Na in PT
Na-K ATPase
499
Protein excretion is high in what 3 conditions
MS, Hemoblobinemia, Myoglobinemia
500
Patient without Parathyroid will excrete ___ phosphate than normal
Less
501
How is phosphate reabsoprtion regulated
Hormones: PTH decrease Tm -> More secretion, excretion
502
How is the Na-K ATPase the driving force for Na absorption
(1) Decrease in intracellular Na; (2) Decrease in membrane potential
503
How does inulin concentration change in tubular fluid of PT
Increases, no reabsorption
504
How is HCO3- pumped out to ISF in PT
HCO3/Na cotransporter
505
Anion transport in PT occurs predominantly by
Diffusion via paracellular route
506
Cl is passively reabsorbed in PT due to
Concentration gradient created by water reabsorption; Electrochemical gradient created by Na reabsorption
507
What favors Anion transport via Paracellular Space
Leaky epithelium
508
Filtration and Reabsorption of Mannitol
Freely filtered, but not reabsorbed -> Reduces water reasbsorption and increases excretion
509
When does Bicarb begin to be absorbed more rapidly
After transition from PCT to PST
510
GFR x Pin =
VL x Tfin
511
What drives water reabsorption in PT? What facilitates this?
Osmotic gradient facilitated by leaky epithelium with high hydraulic conductivity (high Kf)
512
Substances that are freely filtered, but not reabsorbed, can increase ___ and cause ___
Increase osmolarity and cause diuresis
513
Mutation in what causes Familial Renal Glucosuria
SGLT1/2
514
3 Causes of Glucosuria
(1) Pregnancy; (2) DM; (3) Familial Renal Glucosuria (SGLT mut)
515
Reabsorption of what ions follow Na to maintain electroneutrality
Chloride and Bicarb
516
Changes in Cl and Bicarb absorption from PCT to PST
Cl absorption reduced, Bicarb is absorbed more rapidly
517
Bicarb reabsorption requires
Active secretion of protons
518
Primary role of PT
Reabsorb most of the filtered water and solutes
519
What accounts for majority of O2 consumption by kidney
Sodium reabsorption
520
Poorly permeant solutes can serve as
Diuretics
521
Which segments of nephron actively secrete H+ into lumen
PT, DT, and CD
522
Glucose reabsorption across apical membrane is coupled to
Na
523
Result of Na-K ATPase activity
Driving force for Na absorption (Decrease in intracellular [Na], Decrease in membrane potential)
524
How does Glucose cross apical membrane
Sodium-Glucose Cotransport: SGLT1/2
525
What percent of Bicarb is reabsorbed in PT
95%
526
Threshold for Phosphate Reabsorption
Low, regulated by plamsa concentration and hormones
527
Only quantitatively important substance whose transport is directly coupled to metabolic energy in PT
Na
528
How does PAH concentration change in tubular fluid thru PT
Increases more than Inulin b/c not reabsorbed and actively secreted
529
How is urea reabsorbed in PT
Passively, but slow: only 50%
530
Effect of Mannitol infusion
Increases osmolarity -> Filtered -> Reduces water reabsorption and increases excretion
531
How does Bicarb concentration change in tubular fluid thru PT?
Decreases, high reabsorption
532
Where are Na-K pumps exclusively localized?
Basolateral membrane
533
How does change in UF affect Urea clearance
Increase in UF increases Urea clearance
534
Entire plasma volume is filtered __ times thru glomerulus each day
60 times (5 times for whole body fluid)
535
How does Inulin concentration change with distance from Glomerulus
Increases
536
VL =
(GFR x Pin) / Tfin
537
Leaky epithelium of PT favors
Anion transport via Paracellular Space
538
What drives Cl transport in PT
Due to rapid Na absorption, luminal fluid in PT is 5mV more negative than interstitial fluid
539
AA absorption across luminal membrane is coupled to
Na gradient
540
While 66% of fluid is reabsorbed in PT, only ___% of Cl is reabsorbed due to ___
60%, due to active transport of HCO3
541
Chloride, K, and Urea are reabsorbed by
Passive transport
542
2 important luminal Na channels in PT
Na-H exchanger, Na-Glucose cotransporter
543
How do Organic Acids cross luminal membrane
Co transport with Na
544
Transporters for Mannitol
None
545
Major solutes that contribute to isotonic reabsorption in PT
Sodium, Chloride, Bicarb
546
How do AA's cross luminal membrane
Na-AA cotransport
547
How does Cl concentration change in tubular fluid thru PT
Slight increase due to Bicarb reabsorption
548
What proportion of Glucose is reabsorbed in PT
All, until reaches threshold
549
In PT, H+ secretion is mediated by
Apical Na-H exchanger (driven by Na gradient)
550
HCO3- reabsorption is preferred over __, and driven by ___
Cl-, H+ secretion
551
How does massive solute reabsorption affect osmolarity of tubular luminal fluid and interstitial fluid
Slight decrease in osmolarity of tubular luminal fluid and increase in interstitial fluid
552
What percent of AA's are reabsorbed in PT
98-99.5
553
GFR - Reabsorption [+ Secretion] =
Rate of flow into loop of Henle
554
Rank in order of most absorbed in PT: Bicarb, Inulin, AA's, Glucose, PAH, Cl
Glucose, AA's, Bicarb, Cl-, Inulin, PAH
555
How is Na absorbed from tubular lumen in PT
Passively down apical membrane sodium channel
556
What drives Bicarb/Cl exchanger in DCT/CD
Increase in intracellular Bicarb
557
Which has bicarb channel in luminal membrane: alpha or beta intercalate
Beta
558
Under high acidosis conditions, DCT/CD cells express new
H transporter: H-K ATPase or Proton Pump
559
Why is Cl reabsorbed in DCT/CD
Na reabsorption is greater than K secretion, therefore Cl is reabsorbed
560
Liddle's Syndrome is characterized by
Increase Na reabsorption and K secretion
561
How does Aldosterone increase Na reabsorption
(1) Increases number of luminal Na channels; (2) Increases basolateral Na/K; (3) Increases ATP synthesis
562
On which parts of nephron does Aldosterone act
DCT/CD
563
How does Na reabsorption affect K secretion in DCT/CD
Decrease Na reabsorption results in higher lumen-negative transepithelial voltage = K secretion
564
% of filtered load received by DCT/CD of Water, NaCl, KCl, and Urea
10%, less than 10, less than 10, 50
565
What is Conn's Syndrome
Aldosterone secreting tumore
566
What is Addison's disease
Complete absence of Aldosterone
567
How does plasma Ang 2 affect Aldosterone secretion
Low plasma AngII Decreases Aldosterone secretion
568
Which has proton channel in luminal membrane: alpha or beta intercalated
Alpha
569
Electrical acivity of electrically conductive Na channel
Makes lumen more negative; Membrane is depolarized
570
Where is the electrically conductive Na channel present
In both DCT and CD
571
ADH stimulates what in ThickAL
Na-K-2Cl cotransporter (and thus reabsorption of Na)
572
Aldosterone increases what 3 channels
(1) Na/K ATPase; (2) Luminal K; (3) Lumina Na
573
What do Thiazide diuretics block
Na-Cl cotransporter
574
NaCl reabsorption in ThinAL
Strong: 2/3 received volume
575
What blocks Na-K-2Cl cotransporter
Loops
576
Major luminal transporter in ThickAL
Na-K-2Cl
577
Which cell type exchanges Na and K
Principal Cells
578
How does Aldosterone affect K
Increases secretion in DCT/CD
579
Epithelial cells in ThickAL
Thick, many mitochondria
580
Epithelial cells in ThinAL
Thin, few mitochondria
581
How does plasma K affect Aldosterone secretion
Increased plasma K increases Aldosterone secretion
582
Osmolarity change in ThinAL
Drops due to loss of NaCl
583
___ increases flow and Na output into distal tubule, therefore, ___
Loop diuretics, Increase K secretion
584
Which cell type exchanges H+ and Bicarb
Alpha-Intercalated
585
2 Regulatory factors of K secretion in DCT/CD
Increased flow by diuretics inc. K secretion; Decreased Na reabsorption (diuretics) results in higher lumen-negative transepithelial charge
586
Amiloride and Triamterene block
Electrically conductive Na channels
587
Maximum of 1200 mOsm is due to what components
600 mOsm Urea, 600 mOsm NaCl
588
How is switch of H-ATPase and HCO3-Cl exchanger achieved
Activation of two types of intercalated cells
589
Where do Furosemide and Bumetanide act
Cl site in N-K-2Cl cotranspoter in ThickAL
590
How do plasma ACTH levels affect Aldosterone secretion
Low plasma ACTH levels decrease Aldosterone secretion
591
Where is the Na-Cl transporter present
Only in DCT
592
What stimulates Na-K-2Cl cotransporter
ADH
593
Active transport in Thin Ascending and Thin Descending Limbs
None
594
3 other channels in ThickAL besides Na-K-2Cl and Na-K
Basolateral Cl channel (reabsorb); Basolateral K-Cl cotransporter (reabsorb); Apical K (secrete)
595
How is Bicarb reabsorbed in DCT/CD
Bicarb/Cl exchanger
596
How is H+ secreted into lumen in DCT/CD
Active transport (against high gradient)
597
Permeability of TDL to NaCl, Urea, Water
Minimal for NaCl and Urea, Highly permeable to water
598
___ prevent membrane depolarization; no increase in ___
Amilorides, K secretion
599
How does increased flow to DT/CD affect K secretion
Increases
600
2 transport mechanisms for Na reabsorption in DCT/CD
Electrically conductive Na channels; Na-Cl cotransporter
601
What is driving force for NaCl reabsorption in ThinAL
Osmotic Gradient
602
Net result of DCT/CD action if impermeable to water
Dilution of Urine
603
3 Manifestations of Conn's Syndrome
Hypokalemia, Hypernatremia, HTN
604
Under Alkalosis conditions, what channels switch directionality
H-ATPase and HCO3-Cl exchanger
605
2 differences between H+ secretion in proximal vs distal
In distal, H+ is secreted against high gradient actively; Also, distal epithelium is impermeant to diffusion
606
What does Addison's disease tell us about Na reabsorption and K secretion
Not entirely dependent on Aldosterone
607
___ block electro-neutral Na transport, without ___
Thiazides, affecting membrane depolarization
608
What generates H+ in DCT/CD
Cellular Carbonic Anhydrase
609
What blocks the Na-Cl cotransporter
Thiazide Diuretics
610
What blocks the electrically conductive Na channels
Amiloride, Triamterene
611
Reabsorption/Secretion of Na, K, Cl in DCT/CD
Na actively reabsorbed, K is secreted, Cl is reabsorbed
612
Permeability of TAL to NaCl, Urea, Water
Extremebly water impermeable, Impermeable to Urea, Permeable to NaCl
613
Driving force for Na-K-2Cl transporter
Na electrochemical gradient (set up by Na-K ATPase)
614
What increases ANP
Atrial Stretch; Plasma Pna increase
615
Renal Na excretory system responds __ to changes in Na input
Relatively slowly
616
Response to increases in arterial pressure on urinary Na excretion in Isolate Kidney scenario
2-3 fold increase in Na output by 30-50 mmHg change in arterial pressure
617
Effect of changes in pressure on Na excretion in Isolated Kidney vs Intact System
Takes very large increase in pressure in isolated kidney, but only a very small increase in pressure in intact system
618
Where are Neural Stretch Receptors
In large veins
619
Change in BW over short period indicates
Change in Na balance
620
3 Actions of ANP
(1) Dilation of Aff, Constriction of Eff - Inc GFR; (2) Inhibit Aldo secretion; (3) Inhibit Na channel phosphorylation in DT/CD
621
Primary Diabetes Insipidus is associated with low plasma
ADH level
622
ECFV is directly proportional to
Total Body Na content
623
How do ECF, Sympathetic, Renal Arterial BP affect Renin release
Decreased ECFV, Increased Sympathetic firing, Decreased Renal Arterial BP all increase Renin release from JG Cells
624
Effect of ANP on Afferent and Efferent Arterioles
NPR1 causes dilation of Afferent, but constriction of Efferent -> Inc GFR
625
Pna =
(Amount of ECF Na) / ECFV
626
At constant Pna, ECFV = ____
Amount of ECF Na+
627
How long does it take to restore water balance after drinking 1 L pure water (change in plasma osmolarity)
1-2 hours
628
How is Aldosterone release affected by K, Angiotensin, and Na
Release stimulated by plasma K and Angiotensin; Inhibited by plasma Na
629
How do changes in GFR affect Na excretion
Increase in GFR increases Filtered Load and amount of Na excreted
630
ANP has exact opposite effect of
Aldosterone
631
Change in ECFV in response to Na intake is also
Slow
632
Receptors for ANP
NPR1/2 - Guanylate Cyclase cGMP mechanism
633
3 causes of Na imbalance
Diarrhea, Excessive Sweating, Diuretics
634
How does natriuetic hormone affect Na reabsorption
Decreases reabsorption -> Promotes excetion of Na and H20
635
3 Major "Hypovolemic Hormones"
AVP, Renin, NE
636
PV determines mean circulatory filling pressure, and therefore __
CO
637
Effect of Ouabain like factor
Diuresis and Natriuresis
638
Nephrongenic Diabetes Insipidus is associated with elevated
Plasma ADH
639
Timeframe of Aldosterone effect on Na reabsorption
Slow, not likely to play a role in rapid regulation of Na excretion
640
What does the difference in effect of arterial pressure on Na excretion in Isolated vs Intact systems suggest?
Pressure natriuresis is synergized with reduced formation of renin, ang 2, and aldosterone
641
How does ANP decrease Na reabsorption
In DCT via NCC; In CD via cGMP-mediated ENaC phosphorylation
642
How do burn patients get edema
Inc Endothelial permeability -> Flux of Albumin and Fluid into ISF
643
Timeframe of balance restoration after ingestion of water vs isotonic saline
Water changes osmolarity, 1-2 hours corrected; Isotonic saline increases total Na, 2-4 days corrected
644
What ion is lost in diarrhea
HCO3
645
Is sweat isotonic?
No
646
ECFV =
(Amount of ECF Na) / Pna
647
Is vomit isotonic?
Yes
648
What percent of filtered load of Na is reabsorbed in LOF? DCT/CD?
28%, 7%
649
Change in Pna occurs only when
Gain or Loss of Na exceeds thirst mechanism and kidney's ability to correct
650
Activation of Arterial Baroreceptors -->
Pituitary --> AVP
651
Auscultation signs of edema
S3, Pulmonary Edema
652
How does Angiotensin 2 Increase Na Reabsorption
Proximal Na:H exchanger
653
Normal Blood Volume? Volume that causes Edema? Death?
15, 20-25, 10-12
654
Atrial Stretch Receptor Activation -->
Signal via Vagus -> Sympathetic to kidneys, ANP, decreased AVP?
655
Activation of Neural Stretch Receptors in Large Veins -->
Signals Pituitary to regulate AVP --> NK2C channels in ThickAL
656
2 Effects of NE
(1) Inc Aff and Eff arteriolar tone -> Dec GFR; (2) Inc Na, H20 reabsorption by proximal tubule
657
Direct effect of Angiotensin II
Inc Na, H2O reabsorption by proximal tubule
658
How long does it take to restore balance after 1 L of isotonic saline ingested
2-4 days
659
More severe increase in ECFV causes
Pulmonary Edema
660
Edema requires ECF increase of
2.3-3 L
661
Signs of ECFV depletion
Incr HR, Decr BP, Orthostatic incr in HR or Decr in BP
662
Effect of hypotonic fluid loss on TBW, ICFV, ECFV
All decrease
663
High Pressure Sensors of Decr ECV
Carotid Sinus, Aortic Arch, JGA
664
__ of TBW and __ of BW is ECFV
1/3 TBW, 0.2 BW
665
It would take __ liters of pure H2O loss to produce same change in ECFV as 2 liter loss of isotonic fluid
6 liters
666
___ determines size of ECFV
TBNa
667
Usually Hyper-Natremia is caused by ___, rather than ____
Excess water loss, rather than by Na gain
668
How is loss of water (no change in TBNa) distributed
2/3 to ICFV and 1/3 to ECFV
669
What causes disproportionate increase in BUN relative to Creatinine
Volume depletion
670
__ of TBW and __ of BW is ICFV
2/3 TBW, 0.4 BW
671
What type of Hyponatremia does Hypothyroidism cause?
Euvolemic Hypo-osmolar
672
Main solute in concentrated urine
Urea, not Na
673
Lab test to measure ECFV
None readily available
674
How is retained water (no change in TBNa) distributed
2/3 to ICFV and 1/3 to ECFV
675
Volume response depends on mechanisms that sense changes in
Effect Circulating Volume
676
What type of Hyponatremia is caused by Severe HypoKalemia
Hypo-volemic Hypo-Osmolar
677
Changes in TBNa are synomymous with changes in
ECFV
678
Na and associated anions __ are major solutes of ECF
Cl and HCO3
679
What type of Hyponatremia is caused by Acute and Chronic Renal Failure
Hyper-volemic Hypo-osmolar
680
EuvolemicHypo-osmolar Hypo-natremia is due to
Water retention due to autonomous or altered regulation of ADH release
681
What % of TBV is in arterial compartment
15%
682
Gastric losses are rich in __ and would be associated with
HCl, Metabolic Alkalosis
683
Hyper-Natremia with Uosm less than 300 mOsm/kg is
DI (central/nephrogenic), Water diuresis
684
Which is triggers homeostasis first, incr ECF osmolarity or decreased ECV
Incr in Osmolarity
685
Intestinal fluid is rich in ___ and would result in ___
HCO3-, Normal AG Metabolic Acidosis
686
___osmotic fluid is lost with diarrhea or vomitting
Iso-osmotic
687
Hyperosmolar Hyponatremia is usually caused by
Hyperglycemia, Hypertonic Mannitol
688
ICFV change in isotonic losses/volume depletion
None
689
Isotonic losses or gains change __ but not __
ECFV, but not ICFV
690
Vomitting and diarrhea are examples of loss of ___ fluid
isotonic
691
__ of ECFV and __ of BW is PV
1/4 of ECFV, 0.05 BW
692
Change in ECFV and ICFV due to ingestion of Na
Expansion of ECFV w/ little or no change in ICFV
693
__ of ECFV and __ of BW is ISFV
3/4 of ECFV, 0.15 BW
694
Low Pressure Sensors of Decr ECV
Cardiac Atria, Pulmonary Vasculature
695
Iso-Osmolar Pseudohyponatremia is caused by
Severe hyperlipidemia, Hyperproteinemia
696
Expected HCO3, pCO2 changes for Acute Respiratory Alkalosis
HCO3 decreases 2 mEq for each 10 mm decrease in pCO2
697
Type 1 (Distal) RTA is caused by __ and causes ___
Defective H-ATPase, decreased acid secretion
698
For simple acid-base disorders, pC02 and HCO3 always
change in same direction
699
Acid Base disorder caused by Hyperaldosteronism
Metabolic Alkalosis
700
2 disorders with elevated Bicarb (>30)
Metabolic Alkalosis and Chronic Respiratory Acidosis (with kidney compensation)
701
How does plasma anion gap change with respiratory disorders
Doesn't
702
__ % of Bicarb is reabsorbed in PT via __
90% via Na-H antiporter (Na is driving force)
703
If PAG is normal in Metabolic acidosis
Might be kidney not making NH4+, or Losing Bicarb by Diarrhea
704
What inhibits Na channel in principal cell of cortical collecting duct?
Amiloride, Triamterene
705
Isohydric principle
All buffers change in same direction
706
Metabolic Alkalosis is ___ Bicarb
Increased
707
What is synonymous with send a bicarb into blood
Proton pumped into urine that came from intracellular Carbonic Anhydrase
708
How does renal failure affect acid base balance
Reduced GFR - Decreased Ammonium excretion
709
What is invariably present in Simple Acid-Base disorders
Compensation
710
What must accompany NH4+ in urine
Chloride
711
Anion Gap if you lose Bicarb directly in stool
None b/c there's no unmeasured anion
712
Etiology of Metabolic Alkalosis
Loss of H+ into GI or into urine
713
When A- from HA is excreted into urine
Normal Plasma Anion gap, increased plasma chloride
714
Respiratory Acidosis is __ CO2
Increased CO2
715
When will you have lower or negative UAG
If you've lost bicarb by diarrhea, ammonium increases in urine, and chloride accompanies it
716
Major extracellular buffer
Bicarb
717
If Na concentration stays constant, but Chloride conc. changes, then
an acid base disorder is present
718
What puts bicarb back into urine
Cl/Bicarb (Pendrin) in beta-intercalated cells
719
Cl responsive in Metabolic Alkalosis means
Urine Cl
720
Patient with lower GFR develops more severe acidosis following acid load b/c
can't secrete NH4+ as well
721
Expected pH changes for Chronic Respiratory Acidosis
HCO3 increases 4 mEq for each 10 mm increase in pCO2
722
What acid base disorder can dietary protein intake cause
Acidosis
723
Timeframe of H+ excretion, Bicarb reabsorption, and Bicarb generation
Hours to days
724
Expected pH Changes for Acute Respiratory Acidosis
HCO3 increases 1 mEq for each 10 mm increase in pCO2
725
Type 4 (Hypoaldosteronism) RTA is caused by ___ and causes ___
Impaired proton and K secretion, decreased acid secretion
726
What drug inhibits sodium bicarb reabsorption in proximal tubule
Acetazolamide (CAi)
727
Speed and effectiveness of 2 buffering routes in respiratory acidosis
(1) Plasma: rapid but limited, 1-2 mEq/L increase in Bicarb; (2) Kidney excretes NH4, generating new bicarb, delayed 2-3 days
728
Bicarb transporter in beta-intercalated cells
Cl/Bicarb (Pendrin)
729
How long does it take kidney to generate new bicarb ions
2-3 days
730
Acute Respiratory acid base disorders always have __ change in pH than chronic b/c __
Greater change, b/c kidney is slow in compensating
731
Normal HCO3-
22-26 (24mEq/L)
732
Changes in HCO3 and pCO2 in Respiratory Acidosis
Both increase
733
How does CO2 in alpha-intercalated cells affect H secretion/reabsorption
CO2 binds with OH- to form bicarb that is reabsorbed instead of secreted; H+ is the secreted instead of bonding with the OH-
734
When A- from HA is reabsorbed by kidney or retained in plasma
Unmeasured Anion - Increased Plasma Anion Gap, minimal change in plasma Chloride
735
Changes in HCO3 and pCO2 in Metabolic Alkalosis
Both increase
736
HCO3 in Respiratory Alkalosis
Slightly decreased
737
If PAG increases in metabolic acidosis, it's
Lactic Acidosis or some other renally conserved acid anion
738
How does plasma Na change with acid base disorders
Doesn't
739
Where is Bicarb primarily reabsorbed
PT and LOH
740
Cl resistance in Metabolic Alkalosis means
Urine Cl >20 mEq/L (usually >50 mEq/L)
741
Urine Anion Gap =
Na + K - Cl (in urine)
742
Primary acid we produce
CO2 from metabolism of fats and carbs
743
Acid Base disorder caused by Loop or Thiazides
Metabolic Alkalosis
744
Timeframe of intracellular fluid buffer systems
2-4 hours
745
What must be present in simple acid-base disorders
Secondary physiologic compensation
746
Which RTA results from Decreased Acid Excretion?
Type 1 (Distal) and Type 4 (Hypoaldosteronism)
747
Every proton proton pumped into the urin had to come from
Intracellular Carbonic Anhydrase
748
Most common form of chronic alkalosis where the kidney compensates
Pregnancy - Alkalemic
749
2 major buffers of urine
NH4+ and Phosphate
750
Pregnant women acid base
Slightly Alkalemic
751
pH and H+ ranges
6.8-7.8; 16-160 neq/L
752
Changes in HCO3 and pCO2 in Respiratory Alkalosis
Both decrease
753
Decreased Acid excretion is synonymous with
Impaired NH4+ excretion
754
Why can you tell the difference b/t acute and chronic respiratory disorders
Takes kidneys hours to days to compensate
755
Trick for converting [H+] to pH
80 - decimal digits of pH
756
How to distinguish b/t Acute and Chronic
Look at Bicarb: Small change (1-2), then acute; Larger change (4-5) then kidney has compensated and chronic
757
Normal Urine Anion Gap
Positive, 10 mEq/L
758
pKa of Bicarb
6.1
759
Diarrhea results in loss of
Bicarb --> Metabolic Acidosis
760
Normal pCO2
36-44 (40mmHg)
761
Acid Base Disorder caused by Hypokalemia
Metabolic Alkalosis
762
Final excretion of daily aci load occurs primarily in
CD
763
Where are non-Carbonic acids eliminated?
Combined with buffers and secreted by kidneys
764
Indirect estimate of urinary NH4+ excretion
Urine Anion Gap
765
Why is NH4+ trapped in urinary lumen
Lipid soluble
766
Expected pH changes for Chronic Respiratory Alkalosis
HCO3 decreases 5 mEq for each 10 mm decrease in pCO2
767
Compensation for Respiratory disorders occurs by
Alterations in Bicarb concentration
768
Normal Plasma Bicarb
24 mEq/L
769
In simple acid-base disorders, the compensatory mechanisms
Must be present, Never fully correct pH
770
Respiratory Alkalosis is __ CO2
Decreased CO2
771
Metabolic Disorders are processes that directly alter
Bicarb Concentration
772
Urine AG becomes less positve/more negative with
Increasing urinary NH4+ --> Cl must accompany NH4+
773
How to get Bicarb from Total CO2
Subtract 1-1.5
774
Why is Citrate given in acid base
Metabolized to Bicarb
775
How does plasma Cl change with plasma HCO3
Changes equally and inversely
776
How much does Total CO2 exceed plasma bicarb?
By 1-1.5 mEq/L
777
Plasma Cl is altered in which Acid Base Disorders
All except increased Plasma AG Metabolic Acidosis
778
Urine anion gap is an indirect estimate of
Urinary NH4+ excretion
779
pH of 7.4 = what [H]
40 nEq/L
780
Action of Acetazolamide
CA inhibitor - Inhibits Na Bicarb reabsorption in PT
781
How does low pH alon drive bicarb reabsorption
More CO2 in blood freely enters tubular cell - Meaning more reactant to form H+ that goes into Na-H Antiporter
782
Changes in HCO3 and pCO2 in Metabolic Acidosis
Decrease in HCO3- and pCO2
783
[H+] =
24 x pCO2 / [HCO3]
784
HCO3 in Respiratory Acidosis
Slightly increased
785
Only caveat to Urine Chloride in Metabolic Alkalosis
If just took Loop diuretic, urine Cl can't be low b/c block reabsorption
786
Why is Isohydric principle useful
If we know what Bicarb is doing, we know what others are doing (all change in same direction)
787
Acid Base Cells in Collecting Duct
Intercalated cells
788
Where is Carbonic Acid eliminated?
Lungs
789
Which RTA results from Loss of Bicarb
Type 2 (Proximal) RTA
790
Respiratory compensation vs Metabolic Compensation
Respiratory compensations is rapid; Metabolic compensation (by kidneys) is slower over 1-2 days
791
Metabolic Acidosis is ___ Bicarb
Decreased
792
3 Etiology Categories of Metabolic Acidosis
Decreased Renal Acid Excretion; Direct Bicarb Losses; Increased Acid Generation
793
Total CO2 concentration =
Dissolved CO2 + Bicarbonate concentration in venous sample; 25-26 mEq/L
794
Normal Chloride
105
795
3 Factors Affecting K Secretion
(1) [K] across membrane - depends on serum [K]; (2) Electrical gradient deteremined by Na delivery to DT; (3) K permeability of luminal membrane determined by Aldosterone
796
3 Groups of Causes of Hyperkalemia
(1) Excessive K intake; (2) Dec Renal Excretion; (3) Internal Redistribution
797
K imbalance in Congenital Adrenal Hyperplasia
Hypokalemia
798
How is K reabsorbed in ThickALOH, and what else travels thru this route?
Paracellular Diffusion, also Na+, Ca2+, Mg+
799
5 Causes of Internal Redistribution of K leading to HyperK
Insulin Def., B2 blockade, Hypertonicity, Acidemia, Cell lysis
800
Three ways to move K outside body in Hyperkalemia Tx
Diuretics, Resins (cation exchange), Dialysis
801
What eliminates effect of DT flow rate on K secretion
Low K diet
802
Skeletal muscle clinical manifestations of Hypokalemia
Weakness, Rhabdomyolysis
803
When are diuretics usually used for hypokalemia
K sparing in cases of chronic hypokalemia
804
K imbalance in Cushing's
Hypokalemia
805
K-related channels in ThickALOH
NaK2Cl on luminal border; K channel on luminal border; Na-K ATPase on basolateral border
806
What channel does Bartter's affect?
Na-K-2Cl
807
What 3 factors promote K movement across cells
Plasma [K], Insulin, Epinephrine
808
What determines the number of K channels in luminal membrane of DT/CD
Aldosterone
809
Hypoaldosteronism will cause what K imbalance
Hyperkalemia (decreases secretion)
810
Three ways to move K inside cells in Hyperkalemia tx
Insulin, Beta agonists, Bicarb
811
K imbalance in Renal Artery Stenosis
Hyper-reninemia - Hypokalemia
812
Metabolic Acidosis causes what change in K
H+ enters cell, K exits
813
2 Actions of Aldosterone in Principal cells
(1) Adds ENaC (in) and ROMK (out) channels to luminal surface; (2) Stimulates Na-K pump -> Creates electronegativity -> Reabsorption of Na thru epithelial channel (ENaC)
814
Major site of K reabsorption
PT
815
K imblanace in Renin-Secreting Tumor
Hypokalemia
816
Onset and duration of Kayexalate in Hyper K tx
2-3 hours, 4-6 hours
817
What K imbalance is caused by decreased plasma osmolality
Hypokalemia
818
How does increase in Plasma Osmolality change K balance
(1) Fluid shifts out cell and drags K with it; (2) Loss of water causes conc. gradient, K exits down gradient passively
819
What beta agonist is used for Hyperkalemia? How does it work?
Albuterol - Activates Na-K pump via beta 2 receptor
820
At what plasma [K] will you see sine wave morphology
12 mEq/L
821
K imbalance in Bartter's, Gitelman's
Hypokalemia
822
Rapid infusion of K can cause
Cardiac Arrhythmias
823
K imbalance in Conn's Syndrome
Primary Hyper-Aldosteronism - Hypokalemia
824
How does insulin affect K movement
Causes movement into cells - Simtulates Na-H exchange - This activates Na-K ATPase
825
EKG changes in Hyperkalemia
(1) Peaked T wave; (2) Wide QRS, Short QT, Long PR; (3) Further wide QRS, absent P wave; (4) Sine Wave
826
What K imbalance is caused by renal failure
Hyperkalemia - Impaired secretion
827
4 significant locations of intracellular K
Muscle, Liver, RBC, Bone
828
Renal clinical manifestations of Hypokalemia
Nephrogenic Diabetes Insipidus
829
Onset and duration of Furosemide in HyperK tx
5 min, 2 hours
830
At what plasma [K] will you see peaked T wave
6 mEq/L
831
How does Hyperaldosteronism affect K balance
Hypokalemia due to increased Aldosterone
832
Major site of K secretion
CD
833
What potentiates the affect of DT flow rate on K secretion
High vs Low K diet
834
How does rapid cellular proliferation affect K balance?
Rapid intake -- Hypokalemia
835
Onset and duration of Ca2+ for HyperK tx
1-3 mins, 30-60 mins
836
Inhibiting this channel will inc. postive charge in lumen, prevent K secretion
ENaC
837
Onset and duration of Albuterol for HyperK tx
30 mins, 2-4 hours
838
2 classes of K-sparing diuretics used for Hypokalemia
(1) Aldosterone R Blockers; (2) ENaC inhibitors
839
How does too much Na reabsorption affect K secretion
Not enough Na enters ENaC on Principal cells, and there is a small electochemical gradient that is necessary to drive K secretion
840
At what plasma [K] will you see wide QRS, short QT, long PR?
8 mEq/L
841
Clincial manifestations of Hyperkalemia result primarily from
Depolarization of resting Vm in myocytes and neurons
842
Prolonged depolarization from Hyperkalemia decreases
Na permeability thru inactivation of V-gated Na channels - Reduction in membrane excitability
843
Causes K movement into cells - Simtulates Na-H exchange - This activates Na-K ATPase
Insulin
844
How does alpha receptor affect K movement
Inhibits Na-K ATPase, so prevents movement of K into cells
845
How do ENaC inhibitors tx Hypokalemia
Inhibiting this channel will inc. postive charge in lumen, prevent K secretion
846
Which has greater effect on K: Metabolic acidosis due to Organic Acids or Mineral Acids
Mineral Acids
847
How does High K diet affect amount of K secreted for given DT flow rate
Increases
848
How does NG suction affect K balance
Hypokalemia due to increased Aldosterone
849
How do Bartter's and Gitelman's affect K balance?
Hypokalemia due to increased distal Na delivery
850
4 Causes of Hypokalemia due to Internal Redistribution
Insulin excess, Catecholamine excess, Alkalemia, Cell proliferation
851
How do acid base disturbances affect K
Changes in extracellular pH produce reciprocal shifts in H+ and K+ across membrane
852
Smooth muscle manifestations of Hypokalemia
HTN, Ileus
853
How does vomitting affect K balance
Hypokalemia due to increased Aldosterone
854
Stimulates Na-K ATPase via B2 receptors - Move K intracellularly
Epinephrine
855
K imbalance in Prolonged Vomitting, NG suction
Hypokalemia
856
Which have greater effect on K: metabolic or respiratory acid base disturbances
Metabolic
857
Daily intake and output of K
100 mEq/d in; 90-95 out kidney, 5-10 out GI
858
Onset and duration of Insulin for HyperK tx
30 mins, 4-6 hours
859
How are diuretics used to tx Hypokalemia
K-sparing diuretics increase K reabsorption
860
Most common clinical cause of Hypokalemia
Exogenous glucocorticoid excess - Steroid Admin
861
K imblanace in Uretral diversion
Hypokalemia
862
K imbalance in Primary Hyper-Aldosteronism
Hypokalemia
863
What K imbalance is caused by increased plasma osmolality
Hyperkalemia
864
Alkalosis causes what change in K
H+ exits cell, K enters
865
EKG changes in Hypokalemia
(1) Flat T wave; (2) Prominent U wave; (3) Depressed ST segment
866
How does Epi affect K movement
Stimulates Na-K ATPase via B2 receptors - Move K intracellularly
867
How and why does distal tubular flow rate affect K secretion
Increase flow = Inc secretion Na delivery to DT
868
How do diuretics (Loop, Thiazide) affect K balance
Hypokalemia due to increased distal Na delivery
869
How is K usually given clinically
KCl, KPO4 - KCl tab or mixed with IV fluids
870
First-line tx of Hyperkalemia
Ca2+ (doesn't lower K, just counters)
871
Amount of Intracellular K
3300 mEq
872
How does Beta receptor affect K movement
Stimulates Na-K ATPase, so moves K into cells
873
How does Na reabsorption affect K Secretion
If more Na is delivered distally, it enters thru ENaC channels in Principal Cells and creates electrochemical gradient favor K secretion
874
Why and How does beta blockade affect K balance
B2 receptors activate Na-K -> Without activation, K not taken up into cell -> Hyperkalemia
875
Hyperaldosteronism will cause what K imbalance
Hypokalemia (increases secretion)
876
4 causes of decreased renal K secretion
Kindey Failure, DT dysfxn, Dec DT flow, Hypoaldosteronism
877
If there is a deficiency in insulin, what channel is impaired and what ion is dysregulated?
Na-K pump is impaired, Elevated K in ECF
878
Isolated PT dysfunctions are rare but typically result from
disorder of specific transport proteins
879
Mutation in AR Hypo-P Rickets
Several leading to increased FGF-23; or Na-Pi Iic transporter
880
2 ways ADH regulates AQP-2
Short-term: reversibly shuttles channel to luminal membrane; Long-term: inc transcription of AQP-2 gene
881
Plasma Na ~
(Total Body exchangeable Na and K) / TBW
882
What causes Vit D-dependent Rickets Type 1
Mutation of 1alpha-Hydroxylase
883
When is Normal Osmolarity Hyponatremia likely to occur
HyperTGemia, Paraproteinemia - when solid phase of plasma is greatly increased
884
To which is ADH release more senstive, Posm increase or decrease in BV
Posm increase: 1% increase in Posm triggers, but takes 7% decrease in BV to trigger
885
Hypernatremia usually develops if
Thirst is impaired or limitation in acess to free water
886
Main defence mechanism against hypernatremia
Thirst
887
Generalized PT dysfunctions are usually accompanied by
cause-specific extra-renal manifestations
888
Changes in Plasma Na are mainly determined by changes in
TBW
889
When is Dilutional Hyponatremia likely to occur?
Glucose in absence of insulin, Mannitol, Glycine
890
Polyuria is defined as
Incr in urine volume > 3L/day
891
__ is always present in True Hyponatremia
Impaired urinary dilution mechanisms
892
How does increase in peritubular capillary hydrostatic pressure affect net reabsorption of Na and water
Reduces
893
Glomerulotubular Balance is the intrinsic ability of tubules to increase reabsorption in response to
Incr tubular load
894
Normal Posm
285-290 mOsm/kg
895
Macro structure of PT epithelial cells
Microvili (brush border); Basolateral surface is thrown into folds - both extend surface area
896
In absence of ADH, urinary osmolarity can be lowered to
40-60 mOsm/kg
897
Non-osmotic stimuli that stimulate ADH release
Dec ECV, Nausea, Pain, Drugs, Corticosteroid deficiency
898
Ang 2 regulates ___ reabsorption and ___ secretion
NaCl and H20; H+ secretion
899
How is insulin taken up by PT cells
Pinocytosis
900
Water Excess =
0.6 x TBW x (1 - [Na]/140)
901
Hyponatremia with volume depletion is caused by
Renal, GI, or Skin losses; Third spacing
902
4 Acquired forms of Nephrogenic DI
(1) Defect in medullary interstitial tonicity; (2) Defect in cAMP generation; (3) AQP-2 downreg; (4) Pregancy
903
Cause of Cystinuria
Mutation of brush border transporter responsible for cysteine, and other AA's
904
Relationship of PHEX, FGF-23, and Na-Pi cotransporter
PHEX inhibits FGF-23, and FGF-23 inhibits Na-Pi cotransporter and Alpha1-Hydroxylase production
905
Proximal Straight Tubule is aka
Parse Recta
906
Osmotic threshold for thirst vs ADH
Slightly higher for thist: 290-295 vs 280-290
907
Reabsorption in PT is dependent on
Volume Status
908
Serum Glucose in Hereditary Renal Glucosuria
Normal
909
2 most important acquired causes of Fanconi Syndrome
Tenofovir, Multiple Myeloma
910
Hyperosmolar Hyponatremia is due to
Presence of other osmotically active substances that cause water movement out of cells = Dilutional Hyponatremia
911
True Hyponatremia occurs as a result of
Incr TBW, either absolute or relative
912
How does X-Linked Hypophosphatemic Rickes present clinically
Rickets in children; Osteomalacia in adults
913
Mutation in X-linked Hypophosphatemia
PHEX
914
___ is present in majority of cases of true hyponatremia
Appropriate or inappropriate increase in ADH
915
Mutation of brush border transporter responsible for cysteine, and other AA's
Cause of Cystinuria
916
Phosphate vs Na: One can be reabsorbed transcellular and para, the other only trans
Phosphate is trancellularly reabsorbed, Na can be either.
917
3 functional segments of PT
S1-initial short segment; S2-remaining PCT and cortical parse recta; S3-medullary parse recta
918
Most common inherited phosphate wasting disorder
X-Linked Hypophosphatemic Rickets
919
Severity of Cystinuria
Relatively benign, rarely causes kidney failure
920
Inc production of FGF-23 by some tumors
Oncogenic Hypo-P Osteomalacia
921
FGF-23 normally inhibits
Na-Pi cotransporter
922
Hereditary Renal Glucosuria is caused by
mutation of SGLT2 Glucose transporter
923
Classifications of PT dysfunction based on mechanism
Generalized vs Isolated Solute Transport Disorders
924
Most important inherited cause of Fanconi Syndrome
Cystinosis - Cysteine not degraded normally
925
Inheritance of Hereditary Renal Glucosuria
Autosomal recessive
926
Water Deficit =
0.6 x TBW x ([Na]/140 - 1)
927
Hyponatremia with Volume Overload is caused by
Decreased ECV: CHF, Kidney failure, Cirrhosis, Nephrotic
928
Normal function of PHEX
Downregulate FGF23
929
What causes Hartnup Disease
Defect in neutral AA transporter (SLC6A19)
930
Parathyroid hormone regulates what in PT
Pi excretion
931
Normal osmostic threshold for ADH release
280-290 mOsm/kg
932
FGF-23 inhibits
Na-Pi cotransporter and alpha-1-hydroxylase
933
Fanconi Syndrome can be __, but is most commonly ___
Inherited, but most commonly acquired
934
Mutation in PHEX results in increased
levels of circulating factor FGF-23 (PHEX normally downregulates)
935
Susceptibility of PT to ischemia
High
936
Osmotic threshold for thirst
290-295 mOsm/kg (slight higher than for ADH)
937
Patient with functional SGLT2 will have glucosuria if
[Glu] exceeds normal threshold
938
How does pregnancy cause Nephrogenic DI
Placental synthesis of Vasopresinase
939
Uosm in response to water deprivation in Primary Polydipsia
Increase
940
Congenital Nephrogenic DI results from mutations in
V2 or Aquaporin 2
941
Cwater =
V x (1 - Uosm/Posm) = V - Cosm
942
Normal Osmolarity Hyponatremia is due to
Limitation of some Na assays when Na is measure in the whole plasma while solid phase of plasma is greatly increased (eg. HyperTGemia, Paraproteinemia)
943
What is Oncogenic Hypo-P Osteomalacia
Inc. production of FGF-23 by some tumors: fibromas, angiosarcomas, hemangiopericytomas
944
3 inherited causes of Isolated Phosphate Reabsorption defect
(1) X-linked hypophosphatemia; (2) AD Hypophosphatemic Rickets; (3) AR Hypophosphatemic Rickets
945
Acquired cause of Isolated Phosphate Reabsorption defect
Oncogenic Hypophosphatemic Osteomalacia
946
Cosm =
Uosm/Posm x V
947
Most common mutation related to phosphate reabsorption
X-Linked Hypo-P
948
Why is PT highly susceptible to ischemia
ATP dependence, Polarized structure of cells
949
K moving paracellularly is an example of
Simple diffusion requiring electrochemical gradient
950
Mutation in FGF-23
AD Hypo-P Rickets
951
In PT, 33% of Na is reabsorbed via ___, the rest by
33% via transporter proteins, the rest passively by solvent drug via paracellular route
952
Hormonal Function of PT
Final pathway in synthesis of active Vit D
953
Most common electrolyte disorder
Hyponatremia
954
Where is 100% of glucose reabsorbed
PT
955
Mutation in AD Hypo-P Rickets
FGF-23
956
How quickly does ADH insert new AQP-2 channels
within minutes
957
Mitochondria in PT epithelial cells
Rich to provide sufficient energy for mass reabsorption
958
Hyponatremia with normal volume status is caused by
Too much ADH (SIADH, Glucocorticoid def., Hypothyroidism)
959
Which are more severe: Generalized or Isolated PT Dysfunctions
Generalized
960
Hypoosmolar Hyponatremia is due to
Always due to impaired urinary dilution mechanisms
961
"Generalized" PT dysfunction is usually due to
Defect in energy generation (Na-K ATPase) or dysfunction of cellular organelles affecting transport recycling
962
25% of Na in PT is reabsorbed by what exchanger
Na-H
963
mutation of SGLT2 Glucose transporter
Hereditary Renal Glucosuria is caused by
964
What percent of Phosphorus is reabsorbed in PT
80%
965
FGF23 regulates what in PT
Pi excretion
966
4 Causes of Loss of Medullary Hyperosmolarity
(1) Diuretics; (2) Excessive delivery of fluid into LOH; (3) Decreased urea production; (4) Age, renal failure
967
Ability of kidneys to dilute or concentrate urine depends on
Difference between osmolar clearance and clearance of water
968
Activation of V2 in CD results in
insertion of Aquaporins into luminal membrane
969
Actual fluid flow - Cosm =
Free water clearance
970
ADH receptor in Epithelial cells of CD
V2
971
ADH responds to both
Posm, ECFV
972
At what plasma osmolarity does AVP reach max
295 mOsm
973
At what plasma osmolarity is AVP detectable
270-285 mOsm
974
AVP increase requires what threshold of ECFV loss
10-15% decrease in ECFV
975
Cause of Osmotic Diuresis
Hyperosmotic Plasma
976
Central Diabetes Insipidus results from
Pituitary gland doesn't release AVP
977
Common symptom of decreased ability to concentrate urine
Nocturia
978
Complications of Polydipsia
Hyponatremia, Coma, Death
979
Cwater =
UF x (1 - Uosm/Posm)
980
Dec PV after GI loss causes ___, but decreased plasma osmolarity causes ____
Inc AVP, Dec AVP
981
Difference between osmolar clearance and water clearance is
Free Water Clearance
982
How does ADH affect Posm, Uosm in Osmotic Diuresis
Remains: High, High
983
How does ADH affect Posm, Uosm in Primary Polydipsia
Low to Normal, Low to High
984
How does CD help with Medullary Hyperosmolarity
Active transport of Na into ISF
985
How does GI fluid loss lead to hyponatremia
(1) AVP release in response to volume; (2) Dilution of plasma; (3) Inc ECF volume; (4) Reduced osmolarity, Hyponatremia
986
How does heart failure cause hyponatremia
Loss of pressure stimulates hypovolemic hormone release
987
How does IMCD help with Medullary Hyperosmolarity
Passive diffusion of urea into ISF
988
How does liver failure cause hyponatremia
Loss of PV stimulates hypovolemic hormone release
989
How does Thick AL help with Medullary Hyperosmolarity
Active NaCl transport, Co-transport of K and Cl into ISF
990
How does Water Deprivation affect Posm, Uosm, and ADH in Nephrogenic DI
Increase, No change, Increase
991
How does WD affect Posm, Uosm, and ADH in Osmotic Diuresis
Inc, Inc, Inc
992
How does WD affect Posm, Uosm, and ADH in Primary DI
Increase, Remain low, No change
993
How does WD affect Posm, Uosm, and ADH in Primary Polydipsia
Normalize, Normalize, Increase
994
If free water clearance is negative, it means
Urine is being concentrated and BW is retained
995
If Uosm is greater than Posm
Negative Cwater -> Concetrated Urine -> Dec Posm
996
If Uosm is less than Posm
Positive Cwater -> Dilute urine -> Inc Posm
997
In condition of sever ECFV loss, it doesn’t matter what ___, ___ will rise
Doesn’t matter what serum osmolarity is, AVP levels will rise
998
Manifestations of Hyponatremia
Lethargy, Hyporeflexia, Mental confusion
999
Mutations that can cause Nephrogenic Diabetes Insipidus
V2 receptor, Aquaporin-2 --> CD doesn't respond to AVP
1000
Na imbalance with GI fluid loss
Hyponatremia
1001
Normal Cosm
2 +- 0.5 mL/min
1002
Obligatory Urine volume
.5 L / day
1003
Osmolar Clearance =
(UF x Uosm) / Posm
1004
Osmolar clearance is elevated under condition of
Plasma Hyperosmolarity
1005
Osmolar clearance measures
kidney's ability to concentration urine
1006
Calculated Plasma Osmolarity =
2 x Na + (glu/18) + (bun/2.8)
1007
Positive free water clearance indicates
Dilution of urine and concentration of plasma
1008
Resting Posm, Uosm, and ADH in Osmotic Diuresis
High, High, Normal
1009
Substantial dec in ECFV stimulates ADH release even
under condition of hypo-osmolar plasma
1010
T/F: ADH increases linearly with decreased ECFV
False, logarithmic - Very slow increase at first until threshold met
1011
Thick Ascending Limb is permeable to
Active NaCl transport, (K, Cl)
1012
Thin Ascending Limb is permeable to
Passive NaCl, some urea
1013
Thin Descending Limb is permeable to
H20, some urea
1014
To assess efficacy of kidney to concentrate or dilute urine, must first
quantitate the rate of excretion of solute (using Osmolar Clearance)
1015
Two other conditions besides GI Fluid Loss that lead to Hyponatremia with no change in ECFV
(1) Heart Failure - Loss of pressure stimulates hypovolemic hormones; (2) Liver failure - Reduce PV stimulates hypovolemic hormones
1016
Two special features that contribute to preservation of medullary interstitial hyperosmolarity
(1) Meduallry BF is low; (2) Vasa recta serves as countercurrent exchanges
1017
Tx of Hyponatremia due to GI Fluid Loss
Infusion of Isotonic Saline, avoid quick change
1018
Under condition of severe volume loss, effect of ___ on ___ overides ___
Effect of ECFV loss on AVP overrides osmolarity effect
1019
Urea contributes what % of osmolarity in Medullary ISF
40%
1020
Water clearance is how much
water without any solute is cleared in urine
1021
Water deprivation in DI must be stopped if
BW falls >5%, Posm > 300 mOsml/kg
1022
What can override normal response to plasma osmolarity
Severe decrease in ECFV
1023
What is dilemma with severe volume loss and low serum osmolarity
Low osmolarity inhibits ADH so as to correct; But severe volume loss overrides in order to maintain volume
1024
What signals mediate V2 activity
AC -> cAMP -> PKA
1025
Where are osmoreceptors in the brain that stimulate ADH release in response to increase osmolarity
Supraoptic and Paraventricular Nuclei of Hypothalamus
1026
Where is AVP degraded
PT and Liver
1027
Where is the thirst center in the brain?
Lateral Preoptic Nucleus of the Hypothalamus
1028
Which is more efficient: Clearing water or conserving
Clearing fo sho
1029
Which part of CD is permeable to Urea
Inner Medullary
1030
When do you see Waxy Casts
CHRONIC Kindey Disease
1031
Proteinuria in Renal vs Extra-Renal origin hematuria
Renal Origin Hematuria often associated with proteinuria; absent in extra-renal origin
1032
Cast with bright white line around edges, cracks around sides, broken edges
Waxy
1033
What forms matrix of all casts
Tamm-Horsfall protein
1034
Specific gravity is determined by
Numer and weight of solutes
1035
RBC Casts is Pathognomonic for
Glomerulonephritis
1036
Negative Anion Gap means
GI losses, and kidneys are excreting as much acid as possible into urine
1037
Urinary Anion Gap is an assessment of
Hyperchloremic Metabolic Acidosis
1038
RBC Casts in Renal vs Extra-Renal origin hematuria
RBC casts are pathognomonic for renal origin/glomerulonephritis
1039
Granular Casts represent
Breakdown of cellular debris as it passes thru tubules
1040
Protein in Hyaline Casts is
Tamm-Horsfall
1041
Where is Tamm-Horsfall protein produced
Thick Ascending Limb cells - forms matrix of all casts
1042
Fatty Casts are Pathognomonic for
Nephrotic Syndrome
1043
Crenated RBC's indicate
Concentrated supernatant
1044
What should lead to Pure Nephrotic Urine
Diseases affecting only the glomerular basement membrane in a non-inflammatory manner
1045
Nephritic implies
Active inflammation with cellular infiltration (ie proliferative changes)
1046
Which Bilirubin will not be present in urine
Unconjugated (indirect) b/c not water soluble
1047
Diseases which involve active inflammation/proliferation involving both the mesangium and capillary loop should result in
Nephritic Urine
1048
How will Obstructive Uropathy typically present
Tubular Pattern of Urine
1049
Lipiduria =
Nephrotic Syndrome, Heavy Proteinuria
1050
Tubular Proteinuria
Smaller amounts: Failure to reabsorb low molecular weight proteins in proximal tubule
1051
Flat, six-sided crystals
Cystine Crystals
1052
Renal Tubular Epithelial Cells are hallmark of
Acute Tubular Necrosis (ATN)
1053
Conditions with Urinary WBC's
Commonly UTI; Also Pyelonephritis, Allergic Interstitial Nephritis, Intense Glomerulonephritis
1054
RBC morphology in Renal vs Extra-renal origin hematuria
Dysmorphic in Renal Origin (pass thru glomerulus)
1055
When is Leukocyte Esterase positive?
Increased numbers of Neutrophils in urine
1056
Waxy casts are also known as
Renal Failure Casts
1057
Alternative to measuring proteinuria over 24 hour period
Ratio of urine protein over creatinine is reliable estimate of quantitative proteinuria
1058
What leads primarily to Hematuria
Diseases which have active proliferative inflammation that involve the mesangium
1059
Specific gravity of 1.010 corresponds to what Osmolality
300 mOsm/kg
1060
Tubular Urine
No heavy proteinuria, maybe Microscopic Hematuria, maybe Renal Tubular Epithelial Cells, GRANULAR CASTS, High specific gravity
1061
Type of casts seen in chronic kidney disease
Waxy
1062
Origin of Tamm-Horsfall proteins
Secreted by Tubular Cells
1063
What do Squamous Epithelial Cells indicate in urine
Nothing, can be predominant if vaginal contamination of sample
1064
3+ and 4+ proteinuria suggests
Nephrotic Range Proteinuria
1065
When is specific gravity not a marker of concentration
When there are abnormal numbers of heavy solutes in urine (glycosuria, contrast media)
1066
In metabolic acidosis, urinary pH is below
5.3
1067
What test detects all protein in urine
Sulfosalicylic Acid Test
1068
Renal Tubular Epithelial Cells should make you think
Acute Kidney Injury, ATN
1069
Cellular infiltrate directly injuring tubules, such as Allergic Interstitial Nephritis
Inflammatory Tubulitis
1070
Injury typically caused by Ischemia (ATN)
Non-Inflammatory Tubular
1071
Larger, denser, acellular casts
Waxy
1072
Urine with high specific gravity
Tubular: damage to tubules causing inability to dilute or concentrate
1073
Hallmark of Tubular Urine
Granular Casts
1074
Urine in Nephrotic Syndrome
Proten and Lipid
1075
Clots in Renal vs Extra-Renal origin hematuria
Clots may be present in Extra-Renal origin
1076
Cellular infiltration and Pyuria in Non-Inflammatory Tubular Injury
None or little of either
1077
What is almost invariably present in Inflammatory Tubulitis
Sterile Pyuria
1078
Urinary Anion Gap helps you distinguish
Whether etiology is GI (diarrhea secretion of HCO3-) or Urinary (inability to excrete H+)
1079
Only normal cast in urine
Hyaline Cast
1080
RBC range in normal urine
0-2 rbc/hpf; Negative diptick
1081
Which is found in normal urine, Nitrite or Nitrates?
Nitrate
1082
Are ketones found in normal urine?
No
1083
Mesangial Pattern Urine
Hematuria and probably RBC casts, in absence of major proteinuria
1084
Positive Nitrite suggests
UTI with Nitrate-Reduing Bacteria (gram negative)
1085
Intense Glomerulonephritis is usually a feature of
Lupus
1086
Glycosuria in presence of normal blood glucose implies
Proximal Tubular Dysfunction
1087
Urine pH > 7.5-8.0 suggests
UTI with Urea-Splitting Bacteria (proteus)
1088
When Free Hemoglobin and Myoglobin in urine
Dipstick positive, but urinary sediment will be negative for RBC's
1089
Which Bilirubin is water soluble?
Conjugate (Direct)
1090
What is Pyelonephritis
Infected Tubules
1091
Heaviest proteinuria is found when
source is glomerulus
1092
Triple Phosphate Crystals are associated with
Infection
1093
Diseases affecting only the glomerular basement membrane in a non-inflammatory manner should lead to
Pure Nephrotic Urine
1094
Injury typically caused by Direct Tubular Toxins
Non-Inflammatory Tubular
1095
Normal range of Urinary pH
5-6.5
1096
Most common Uropathogens
Gram Negative Bac
1097
Urinar Casts represent
Precipitates of protein forming in lumen of tubules
1098
Normal range for urinary WBC's
0-4/hpf
1099
Large, plate-like cell with abundant cytoplasm and very small nucleus
Squamous Epithelial Cell
1100
Non-inflammatory Tubular Injury would be typical of
Ischemia (ATN) or Direct Tubular Toxins
1101
Urine: Varying levels of protein, almost invariable hematuria, frequently RBC casts
Nephritic Urine
1102
What is present in urine of Pyelonephritis
Pyuria and Bacteruria
1103
What should result in Nephritic Urine
Diseases which involve active inflammation/proliferation involving both the mesangium and capillary loop
1104
When do you seen Uric Acid Crystals in urine
Normal urine that's been sitting or refrigerated
1105
When are Ketones present in urine
Fasting, DKA, AKA
1106
Negative dipstick for albumin, but positive sulfosalicylic acid test indicates
Light Chain proteinuria (MM)
1107
Cystine crystals are associated with
Always pathologic, associated with very dense nephrolithiasis
1108
Any pathologic process that leads to renal injury should also lead to
Abnormal urinalysis with potential changes in GFR
1109
What does Tubular Proteinuria reflect
Promxial Tubular Dysfunction
1110
RBC Casts are Pathognomonic for
Glomerulonephritis
1111
Nephrotic Range of proteinuira
3.5 grams/24 hours
1112
Large cell with nucleus about same size as WBC
Renal Tubular Epithelial Cell
1113
"Coffin Lid" crystals
Triple Phosphate Crystals
1114
Renal Tubular Epithelial Cells are most commonly found when there is
Acute Tubular Injury
1115
Specific gravity of 1.030 corresponds to what Osmolality
1200 mOsm/kg
1116
Osmolality is determined by (as opposed to specific gravity)
Only the number of solutes
1117
Hyaline Casts are found in healthy persons in states of
Volume Depletion
1118
Diseases only involving the tubules should lead to
Tubular Pattern of Urine
1119
Diseases involving the microcirculation will lead to
Altered GFR, frequently signs of glomerular injury with proteinuria and hematuria
1120
Urine: Heavy proteinuria, Lipiduria, and signs of proliferation/inflammation with hematuria
Mixed Nephritic and Nephrotic
1121
Morphology of Urinary WBC's
Granular cytoplasm, irregular nucleus, "glitter cells"
1122
Diseases which have active proliferative inflammation that involve the mesangium only lead to
Primarily to hematuria
1123
Most common type of Renal Stone
Calcium Oxalate Crystals
1124
Nephritic changes will be manifest in urine by
Varying levels of protein and hematuria, frequently with RBC casts
1125
Elevated levels of plasma conjugated bilirubin lead to
Urinary excretion
1126
Most common cause of positive dipstick for blood is
presence of RBC's in urinary sediment
1127
Normal limit of protein excretion
Less than 150mg/day
1128
What tx do you use in both Primary and Secondary Nephrotic
Supportive measures to control HTN
1129
Most common cause of ESRD requiring dialysis
Diabetic Nephropathy
1130
3 diseases: Subendothelial space or Mesangial Immune Complex formation and complement activaiton with inflammation
Post-Infectious GN, IgA Nephropathy, Lupus Nephritis
1131
Buzzword for Alport Syndrome
Basketweave
1132
Buzzword for MPGN
Tram Tracks
1133
Most important prognostic predictor of nephrotic syndrome
Degree of Proteinuria
1134
Nephrotic patients have __ filtration SA, and ___ change in large pores
Loss of filtration surface, increased number of large pores
1135
Main site of charge hindrance
Anionic charged lamina rara interna, Fenestrate capillary endothelium
1136
Buzzword for Post-Infectious GN
Subepithelial Humps
1137
Subepithelial deposits tend to cause a ___ picture, wherease Subendothelial and Mesangial deposits tend to cause a ____ picture
Nephrotic, Nephritic
1138
Fatty casts are indicative of
Lipiduria of nephrotic syndrome
1139
Tram Tracks is buzzworf for
MPGN
1140
Subepithelial humps is buzzword for
Post-Infectious GN
1141
Foot process effacement is buzzword for
Minimal Change Disease
1142
Most common cause of rapidly progressive GN
Autoimmune Vasculitis
1143
Basketweave is buzzword for
Alport Syndrome
1144
Earliest clinical manifestation of Diabetic Nephropathy
Microabluminuria
1145
BP in Nephrotic vs Nephritic
Elevated in Nephritic
1146
If there is generalized edema, evaluate for
Proteinuria
1147
Podocyte injury occurs in what 2 diseases
Minimal Change, Focal Segmental Glomerulosclerosis
1148
A 24-hour collection of urine will have less than __
150 mg of protein
1149
Tubular disease is associated with proteinuria of ___ proteins
LMW
1150
Nephrotic patients have __ excretion of SMW dextrans, and ___ excretion of LMW dextrans
Lower, higher
1151
Subepithelial space immune complex formation and complement activation, without inflammation
Membranous Nephropathy
1152
4 features of Nephrotic Syndrome
Edema, Proteinuria, Hypoalbuminemia, Hyperlipidemia
1153
Creatinine in Nephrotic vs Nephritic
Elevated in Nephritic, Normal or mild elevation in Nephrotic
1154
Granular casts almost always indicate
significant renal disease
1155
If ___ are present, Fatty casts can have ___ pattern under polarized light
Cholesterol or cholesterol esters, Maltese cross
1156
2 absolute contraindications to renal bx
Bleeding Diathesis, Uncontrolled HTN
1157
4 features of chronic GN
HTN, Renal Insufficiency, Proteinuria, Shrunken Smooth Kidneys on US
1158
Does the dipstick detect microalbuminuria
No, Microalbuminuria is 300 mg/day
1159
Spike and Dome is buzzword for
Membranous Nephropathy
1160
Nephrotic Syndrome mechanisms without glomerular inflammation include glomerular capillary wall deposition in ___, ___, and ___
Diabetic Nephropathy, Amyloidosis, and Light Chain Deposition disease
1161
Casts that can be seen in Nephrotic Syndrome
Hyaline, Granular, Fatty, (WBC)
1162
Muddy brown casts are a type of ___ almost always seen in ____
Granular Cast, Acute Tubular Necrosis
1163
3.5 mg/day 24 hour urine corresponds with what spot urine protein/creatinine ratio
3.5
1164
A spot urine protein/creatinine ratio of less than ___ corresponds with 24 hour urine protein of 150
0.15
1165
Microalbuminuria is defined as
30-300 mg/day
1166
Normal rate of protein excretion
40-80 normal; 150 upper limit of normal
1167
Nephrotic Syndrome mechanisms without glomerular inflammation include subepithelial immune complex formation and complement activation in
Membranous Nephropathy
1168
Macromolecules > ___ nm are completely restricted
4 nm
1169
Uncharged macromolecules < ___ nm filter freely
1.8
1170
Onion skin in spleen =
Lupus
1171
WBC casts are indicative of
Inflammation
1172
Urinary sediment in Nephrotic Syndrome
Inactive - without dysmorphic RBCs or RBC casts
1173
Estimated glomerular pore radius for spherical molecules
42 angstroms
1174
How are proteins reabsorbed in PT
Endocytosis by endothelial cells --> Hydrolyzed in lysosomes into AAs --> Re-enter circulation
1175
Proportion of filtered proteins that are reabsorbed
Almost all
1176
Why do patients with nephrotic syndrome have subcutaneous lipid deposits (Xanthelasma)
Increased hepatic synthesis of cholesterol, TG's and Lipoproteins
1177
Main site of size hindrance for larger molecules
Lamina Densa and Slit diaphragm
1178
Buzzword for Membranous Nephropathy
Spike and Dome
1179
Nephrotic Syndrome mechanisms without glomerular inflammation include podocyte injury in ___ and ___
Minimal Change Disease and Focal Segmental Glomerulosclerosis
1180
Granular casts can result from
Aggregates of plasma proteins or breakdown of cellular casts
1181
Loss of more than ___ of protein per day in urine is defined as Nephrotic
3.5 mg
1182
Buzzword for Lupus Nephritis
Wire Loops
1183
Threshold for protein dipstick
300-500 mg/day
1184
2 causes of xanthelasma
Hyperlipidemia in nephrotic syndrome; Amyloidosis
1185
Upper limit of normal for spot urine protein/creatinine ratio
0.15
1186
Subepithelial deposits tend to cause a ___ picture, as seen most characteristically with
Nephrotic, Membranous Nephropathy
1187
Other than Post-infectious GN, Subepithelial humps are seen in
SLE
1188
Primary Nephrotic syndrome management includes disease modifying tx w/
Corticosteroids and Immunosuppression
1189
Major causes of Membranous Nephropathy
Idiopathic or due to Systemic Disorders: SLE, Hep B, Drugs (Gold, penicillamine)
1190
Onion-skin is buzzword for
HTN nephropathy; Scleroderma
1191
Reduce __ is associated with secondary FSGS
Reduced nephron mass
1192
ApoL1 mutation makes you susceptible to
FSGS
1193
AI w/ immune complexes formed in situ from binding of filtered auto-ab to podocyte m-type PLA2R
Probably pathogenic mechanism causing most cases of Primary Membranous Nephropathy
1194
IF in MCD and FSGS are usually both
negative
1195
Why is effacement of foot process likely mediated by MAC
Intermediary chemotactic fragments, C3a and C5a, are washed away into urinary space
1196
Demographic of Post-Strep GN
School age children, male preponderance
1197
LM of Membranous Nephropathy
Thickening of GBM
1198
If poor response to steroids in MCD, think of
Unsampled focal segmental glomerulosclerosis
1199
Most common demographic of Focal Segmental Glomerulosclerosis
Adult black males
1200
Why no inflammation in Membranous Nephropathy
Complement not activated b/c at a site that is not in contact with circulating inflammatory cells
1201
Thickened GBM w/out increased cellularity
Membranous Nephropathy
1202
Most common cause of Nephrotic Syndrome in Black Adults
64% Focal Segmental Glomerulosclerosis
1203
IF of FSGS
Normal
1204
Membranous Nephropathy vs Post-Infectious GN: Which is nephritic and which nephrotic
Membranous Nephropathy is nephrotic
1205
Diffuse endocapillary proliferation and infiltration by numerous neutrophils
Post-Strep GN
1206
IF of Membranous Nephropathy
Granular subepithelial deposits of IgG and Complement
1207
Complement changes in Post-Strep GN
Low C3, but normal C4 - Demonstrates alternative pathway activation
1208
Suggested pathogenesis of Focal Segmental Glomerulosclerosis
suPAR binds to and activates beta3-integrin, a major podocyte anchoring protein
1209
What causes Spike and Dome appearance
Subepithelial deposits with thin tracts of new GBM separating the deposits
1210
What is hyalinosis in FSGS
Accumulation of leaked plasma protiens and lipids
1211
Which subtype of Focal Segmental Glomerulosclerosis has a rapid onset of nephrotic syndrome with rapid progression to renal failure
Collapsing Glomerulopathy
1212
What causes 75% of nephrotic syndrome cases in children
Minimal Change Disease
1213
Tx of FSGS
Corticosteroids (poor response) and Calcineurin inhibitors
1214
Soluble Urokinase-type plasminogen activator receptor (suPAR) is elevated in serum of 2/3 of patients with
Focal Segmental Glomerulosclerosis
1215
Most common cause of Nephortic Syndrome in Caucasian Adults
Membranous Nephropathy
1216
LM histology of Focal Segmental Glomerulosclerosis
Scarring, Adhesions to bowman's capsule, Occluded cap lumens, Hyalinosis
1217
The Collapsing Glomerulopathy subtype of FSGS is often associated with
HIV infection or drug toxicity
1218
suPAR binds to and activates
Beta3-integrin, a major podocyte-anchoring protein
1219
Prognosis of Minimal Change Disease
Resolves with steroid tx in >90% of kids; Response slow in adults; Recurrence is common
1220
EM of Focal Segmental Glomerulosclerosis
Effacement of foot processes
1221
Minimal change disease causes about__ of nephrotic cases in children
75%
1222
What mutation in AA's confers 10.5-fold higher incidence of Focal Segmental Glomerulosclerosis
ApoL1
1223
Role of suPAR, beta3-integrin, and podocytes in Focal Segmental Glomerulosclerosis
suPAR binds to and activates beta3-integrin, a major podocyte anchoring protein
1224
5 features accompanying Nephrotic Syndrome that indicate FSGS over MCD
Older Age, Hematuria, HTN, Non-selective Proteinuria, Poor response to steroids
1225
Probably pathogenic mechanism causing most cases of Primary Membranous Nephropathy
AI w/ immune complexes formed in situ from binding of filtered auto-ab to podocyte m-type PLA2R
1226
Prognosis of Post-Strep GN
Generally good in children; 40% of adults develop chronic azotemia
1227
Ages of minimal change disease
Very young or very old
1228
Presentation of Membranous Nephropathy
Most with nephrotic syndrome, rest with asymptomatic proteinuria
1229
IF of Post-Strep GN
Diffuse granular deposts of IgG and C3
1230
Most common subtype of Focal Segmental Glomerulosclerosis
Not Otherwise Specified
1231
Demographic of Membranous Nephropathy
Caucasian Male Adults
1232
EM of Membranous Nephropathy
Effacement of FP's and Spike and Dome: Subepithelial deposits with tracks of BM separating them
1233
Top two findings in FSGS
Nephrotic Range Proteinuria, Hematuria
1234
NEP is the target antigen in
Congenital Membranous nephropathy
1235
LM of Post-Strep GN
Diffuse proliferative GN, prominent endocapillary proliferation and numerous neutrophils
1236
m-type PLA2
Immune complexes --> Most primary Membranous Nephropathy
1237
Chronic, slowly progressive disease wih GBM thickening, Subepithelial immune complex deposits, and effacement of foot processes
Membranous Nephropathy
1238
LM, IF, and EM of Minimal Change Disease
LM and IF are negative, but EM shows foot process effacement
1239
Post-Strep GN typically presents with
Nephritic Syndrome
1240
Tea or Cola Colored Urine
Post-Infectious GN
1241
suPAR
Binds Beta3-integrin --> FSGS
1242
Why is it important to differentiate FSGS from MCD
Prognosis is much worse in FSGS
1243
PLA2R is the target antigen in
Primary (idiopathic) Membranous Nephopathy
1244
EM of Post-Strep GN
Subepithelial electron-dense deposits = Humps
1245
Insidious onset of Nephrotic Syndrome in child with good response to steroid tx
Minimal Change Disease
1246
Cornerstone of tx in Minimal Change Disease
Oral Glucocorticoids
1247
What causes podocyte injury in Membranous Nephropathy
Formation of MAC due to auto-Ab binding (to m-type PLA2R)
1248
Time fram of Post-Strep GN after infection
1-6 weeks
1249
2 Podocyte Disorders
Minimal Change Disease, Focal Segmental Glomerulosclerosis
1250
3 basic components of Nephritic Sydnrome
Hematuria, Renal Insufficiency, HTN
1251
3 GBM Diseases
Anti-GBM Disease, Alport's, Thin BM Disease
1252
Ab's to ___ occur in about 80% of patients with DDD
C3 Nephritic Factor
1253
Accumulation and proliferation of cells outside the glomerular tuft which can result in compression of the tuft
Crescents
1254
Age of MPGN presentation
older children and younger adults (7-30)
1255
Anti-GBM Disease is characterized by
Auto-Ab's against epitope in non-collagenous domain of alpha 3 type 4 collagen
1256
As a general principal, MPGN is usually ___ in children, and ___ in adults
Primary in children, secondary in adults
1257
Auto-Ab's against epitope in non-collagenous domain of alpha 3 type 4 collagen
Anti-GBM Disease is characterized by
1258
Berger's Disease is aka
IgA Nephropathy
1259
BM in Alport Syndrome
Abnormally thin, with splintering of lamina densa causing basket weave appearance
1260
Buzz word for Alport Syndrome
Basket Weave
1261
C3 deposition on IF, electron-dense deposits on EM
IF and EM of DDD
1262
C3 levels in MPGN 1 vs DDD
Low in both
1263
C3 Nephritic Factor
80% of DDD cases
1264
Characeteristic feature of IgA Nephropathy
Deposition of IgA1 in MM
1265
Characteristic double contour resembling tram tracks on silver stain
MPGN
1266
Characteristic LM manifestation in glomeruli of RPGN
Crescents in Bowman's space
1267
Clinical manifestation of Endothelial Damage
Hematuria
1268
Correlation between anti-gbm titers and disease activity
None
1269
Crescentic infiltration causes proliferation of
Mononuclear cells and Parietal Epithelial Cells
1270
Crescents in RPGN are composed of
proliferating parietal epithelial cells, macrophages, fibrin; eventually areas of necrosis
1271
Crucial feature of Type 3 RPGN
Negative IF
1272
DDD is differentiated from other forms of GN
EM: Ribbons of dense, dark material deposited w/in GBM
1273
DDD is not caused by ___, but instead by dysregulation of ___
Not by immune complexes, by dysregulation of complement system
1274
Demographic of Anti-GBM disease
Young white males
1275
Demography of IgA Nephropathy
East Asian male children
1276
EM of DDD
Ribbons of dense, dark material deposited w/in GBM
1277
Endothelial cell injury in glomerular capillaries can lead to
Thrombus formation
1278
Glomerular endothelial cell injury and capillary thrombus formation can occur in absence of immune complexes and cause a syndrome called
Thrombotic Microangiopathy
1279
Heterozygous females in X-Linked Alport Syndrome
May have hematuria and thin BM
1280
Histology of Anti-GBM disease
Crescentic necrotizing GN, w/ characteristic linear deposits of IgG along GBM
1281
How are granular deposits in Type 2 RPGN visualized
EM
1282
How are linear deposits in Type 1 RPGN visualrized
IF
1283
How soon after infection will you see nephritic sediment in IgA Nephropathy
Synpharyngitic: 1-2 Days
1284
IF and EM of DDD
C3 deposition on IF, electron-dense deposits on EM
1285
IgA Nephropathy differs from post-strep GN in being
Synpharyngitic
1286
IgA Nephropathy has immune complex deposition in what location
Mesangial location
1287
IgA Nephropathy is differentiated from other forms of GN by
IF: characterstic findings of mesangial IgA deposits, often with C3 and properdin
1288
IgA Nephropathy is typcially triggered by
URTI or GI infection
1289
IgA Nephropathy results in ___ pattern of injury
Mesangioproliferative
1290
Incidence of IgA Nephropathy is increased in patients with
Celiac Disease or Chronic Liver Disease (decreased hepatobiliary clearance)
1291
Is crescent formation due to antibodies or a cell-mediated process
Can be either
1292
Is RPGN a medical emergency
No, but requires prompt dx and tx
1293
It is thought that DDD is a ___ disease, that becomes manifest when ___
Two-Hit, infection or autoimmunity gives rise to excess of immune complexes or complement activation
1294
Location of MPGN Deposits
Subendothelial
1295
Lupus nephritis immune complex deposition tends to occur in what location
Subendothelial
1296
Macular deposits in the eyes and/or acquired partial lipodystrophy
DDD
1297
Mesangial proliferation in MPGN is likely in response to
Circulating immune complexes
1298
Most common MPGN type
Type 1 (80%)
1299
Most common primary GN worldwide
IgA Nephropathy
1300
MPGN diseases have LM appearance combining
Thickened, split GBM w/ a proliferation of glomerular cells and infiltration of inflammatory cells
1301
MPGN has immune complex deposition in what location
Subendothelial
1302
Mutation in Alport Syndrome
Alpha5 chain of Type 4 collagen
1303
One of the most common diseases to have the nephritic-nephrotic phenotype
MPGN
1304
Other notable location of Dense Deposits in DDD
Bruch membrane of eye
1305
Pathogenesis of IgA Nephropathy
Aberrant Glycosylation of O-linked glycans in the hinge region of IgA1
1306
Patients with Anti-GBM disease who have pulmonary and renal involvement
Goodpasture's Syndrome
1307
Plasmapharesis in Type 2 RPGN
not helpful
1308
Post-infectious GN immune complex deposition tends to be in what location
Subepithelial
1309
Presentation of Anti-GBM
Nephritic syndrome, Heamturia, rapid renal failure
1310
Prognosis in DDD
Poor
1311
Prognosis of Anti-GBM disease
Poor - Rapid progressive GN
1312
Prognosis of Type 1 MPGN
Poor, slow progression to ESRD requiring dialysis or transplant
1313
Progression to Fibrous Crescents
Segmental proliferative and necrotizing lesions --> Cellular Crescents --> Fibrocellular crescents --> Fibrous Crescents
1314
Renal Insuff can be manifested by
Oliguria and/or Azotemia
1315
Ribbons of dense dark material within GBM on EM
DDD
1316
RPGN can be characterized by
Type of Glomerular deposits
1317
RPGN with Granular (immune complex) deposits
Primary renal disease, secondary renal disease
1318
RPGN with linear glomerular deposits
Anti-GMB disease, Goodpasture
1319
RPGN with no glomerular deposits
Drug-induced, Idiopathic, ANCA-associated (wegener's or Micrscopic Poly)
1320
Secondary MPGN can be a complication of
Hep C
1321
Single most characteristic feature of Nephritic Syndrome
Hematuria
1322
Systemic form of IgA Nephropathy
Henoch-Schonlein Purpura
1323
Triad of Alport Syndrome
Nephritis, Nerve Deafness, and Lens disorders (all need defective collagen)
1324
Tx of Anti-GBM disease
Plasmapharesis, Steroids, Immunosuppressives
1325
Tx of IgA Nephropathy
Steroids, ACEi's, ARB's
1326
Type 1 MPGN is mediated by ___, causing activation of _____
Immune complexes, activaiton of complement by classical pathway
1327
Type 2 RPGN can be seen in severe cases of
Post-Strep GN, Lupus Nephritis, and IgA Nephropathy
1328
Type 2 RPGN: in addition to crescents, there is
segmental necrosis, mesangial cell proliferation, and exudate w/ leukocytes
1329
Uniform reduction in GBM to about 1/2 of normal thickness
Thin Basement Membrane Disease
1330
What are recruited by damaged endothelial cells in MPGN
Monocytes and Macrophages
1331
What causes tram track appearance
Formation of new BM and entrapment of immune complexes, complement factors, cellular elements, and matrix material
1332
What differentiates MPGN 1 from DDD in IF
MPGN 1 has C3 and IgG, but DDD has just C3
1333
What does IF show in Type 1 MPGN
Granular deposits of C3 and IgG
1334
What frequently precedes the kidney diesease in Dense Deposit Disease
URTI
1335
What frequently precedes the kidney disease in Type 1 MPGN
URTI
1336
What glomerular disease is often associated with Hep C infection
MPGN 1
1337
What is abundantly increased in MPGN
Mesangial Matrix
1338
What is the basket weave
Alport: GBM has several alternating layers of lamina rar and lamina densa
1339
What type of immune complex deposition is injurious to endothelial cells
Subendothelial
1340
Where are IgA complexes primarily deposited in IgA Nephropathy
Mesangium
1341
Where are immunce complexes formed in MPGN? IgA Nephropathy? Lupus?
Outside, outside, outside
1342
Where is new BM formed in MPGN
At the mesangial cell - endothelial cell interface
1343
Which complement pathway is dysregulated in DDD
Alternative
1344
Demographic of SLE
Black Female of child-bearing age
1345
AI necrotizing granulomatous vasculitis of respiratory tract and cause of crescentic GN associated with C-ANCA
Wegener's
1346
Thrombotic Microangiopathy of Glomeruli in small children due to Shiga toxin from E Coli infection
Hemolytic Uremic Syndrome
1347
Most common form of Lupus Nephritis
Diffuse Proliferative (Class IV) - Severe disease
1348
Ab's in Microscopic Polyangiitis
P-ANCA (anti-mpo)
1349
What are Classes I, II, and III of Lupus Nephritis
Minimal Mesangial (rare), Mesangial Proliferative (15), Focal Proliferative (25)
1350
Sudden onset of irritability, lethargy, weakness, pallor, and oliguria 5-10 days following gastroenteritis
HUS
1351
Effect of Microscopic Polyangiitis on kidneys
Glomerulonephritis
1352
First and second most common Classes/Patterns of GN
Diffuse Proliferative (50), then Focal Proliferative (25)
1353
Manifestation of renal involvement of SS
Mild renal dysfunction, Proteinuria, HTN; or Scleroderma Renal Crisis
1354
Which arteries show onion skinning in SS of kidneys
Interlobar arteries
1355
Which Class of Lupus Nephritis has significantly worse renal survivial rate
IV
1356
Immediate consequence of PMN activation by ANCAs
Increased contact and adhesion with endothelial cells and vascular structures
1357
There are granular deposits of ___ in ___ locations in most cases of SLE
Ig and Complement, Subepithelial, Mesangial, and Subendothelial locations
1358
Typical onset of HUS
Sudden irritability, lethargy, weakness, pallor, oliguria; 5-10 days following gastroenteritis
1359
Vascular changes in Scleroderma Renal Crisis associated with poorer outcome
Mucoid Intimal thickening and thrombosis
1360
Patients with Wegener's develop necrotizing granulomatous inflammation in their ____, in addition to ____
Nose, Paranasal sinuses, and Lungs, in addition to Crescentic GN
1361
What are Classes IV, V, and VI of Lupus Nephritis
Diffuse proliferative (50), Membranous (10), Advanced Sclerosing (?)
1362
HUS + Fever and neurological dysfunction (seizures)
TTP
1363
How do you differentiate between TMA and DIC
PT and PTT are normal in TMA, but prolonged in DIC
1364
ANCA-associated GN is usually part of
syndrome with extra-renal signs and symptoms
1365
For SLE, anti-dsDNA and anti-Sm Ab's are less ___ than Anti-nuclear, but much more
Less sensitive, but more specific
1366
Most forms of vasculitis involve on
Arteries
1367
Prevalance of anti-nuclear auto-ab's in normal individuals
15%
1368
T/F: Pauci-immune GN may be ANCA-negative and can occur w/out extra-renal disease
TRUE
1369
PR3-ANCA =
Wegener's
1370
Only approved tx of Lupus by FDA
Aspirin, Glucocorticoids, Hydroxychloroquine
1371
Full House Immunofluorescence
In SLE, staining of deposits with antisera to all 3 Ig's, C3, and Cr
1372
AI small vessel vasculitis cause of pauci-immune crescentic GN associated with P-ANCA
Microscopic Poly
1373
Finding MHA and Thrombocytopenia with no other explananation besides TTP should prompt
Plasmapharesis
1374
Clincially, patients with Thrombotic Microangiopathies have what 3 things
Microangiopathic Hemolytic Anemia, Thrombocytopenia, Often renal failure
1375
Mortality for HUS
4% if treated, poor if not
1376
Which class of Lupus Nephritis is severe? Which is nephrotic?
IV is severe, 5 is nephrotic
1377
What is Onion Skinning? (in context of kidney in SS)
Concentric Sclerosing Intimal thickening of interlobar arteries
1378
Tx of HUS
Transfusions, Dialysis, Supportive measures
1379
Which is ANCA+: PAN or Microscopic Polyangiitis
Microscopic Polyangiitis
1380
A ____ event is likely necessary for endothelial injury with ANCA-associated vasculitis
Synergistic pro-inflammatory event (like exposure to TNF-alpha)
1381
HUS is usually a complication of
intestinal infection of Shiga-toxin producing E Coli
1382
New onset of accelerated arterial HTN and/or rapidly progressive oliguric renal failure
Scleroderma Renal Crisis
1383
Cause of TTP
Deficiency of ADAMTS13 - Cleaving protease of vWF
1384
Demographic of SS
Black women in their 50s
1385
3 general locations affected by Wegener's
URT, LRT, Kidney
1386
Tx of TTP
Plasmapharesis
1387
When both P-ANCA and C-ANCA are present, call it
MPO-ANCA
1388
Medium vessel arteritis (eg classic PAN) causes
renal infarcts and distal glomerular ischemia
1389
Most common and characteristic forms of lupus nephritis involve
the glomeruli
1390
Factor H mutation
Uncontrolled activation of complement with intravascular thrombosis --> HUS
1391
Negative Ab (pauci-immune) is usually in the setting of
Crescentic GN
1392
T/F: Pauci-immune means no Ab's
False, can still have ANCA's
1393
T/F: Patients with Wegener's can also have P-ANCA
True, or be ANCA negative
1394
90% of patients with ANCA-associated Crescentic GN have ___ before they develop symptoms of GN
Flu-like symptoms
1395
Which is usually ANCA positive: Medium or Small vessel vasculitis
Small
1396
2 main types of Thrombotic Microangiopathies
HUS, TTP
1397
Tx of SLE
Steroids, Immunosuppressants: Mycophenolate, Cyclo, MTX, Azathioprine
1398
Vasculitis in SLE
Acute necrotizing vasculitis of small arteries and arterioles with fibrinoid deposits
1399
Histological findings in kidney in scleroderma
Onion skinning, Intimal and Medial proliferation, Fibrinoud Necrosis
1400
Extra-renal signs and symptoms in ANCA-associated GN
Athralgias, Arthritis, Myalgias, Fatigue
1401
Fundamental pathogenesis of Thrombotic Microangiopathy
Loss of Thromboresistance by endothelial cells
1402
Urine feature present in 100% of patients with SLE
Proteinuria
1403
Type of vasculitis caused by Wegener's
Necrotizing
1404
Typical patient with TTP
Older adult - Subacute onset of malaise, faitigue, petechiae, pallor, confusion, nausea, abdominal pain, weakness
1405
Tx of Wegener's
Cyclophosphamide, Steroids, sometimes plasmapharesis
1406
What are Hyaline thrombi
Misnomer of wire loop deposits that protrude into lumen
1407
Microscopic Polyangiitis vs PAN effects on Kidney
MP causes GN, whereas PAN causes macroscopic ishcemia and infarction (thrombosis, aneurysm)
1408
Tx of Scleroderma Renal Crisis
ACEi
1409
Scleroderma Renal Crisis
New onset of accelerated HTN and/or rapidly progressive oliguric renal failure
1410
Eculizamab is used for
Block complement activation (HUS subtype)
1411
Systemic Sclerosis is characterized by
Fibrosis of CT and Vascular Occlusive Disease
1412
Hemolytic Uremic Syndrome is triad of
Microangiopathic Hemolytic Anemia, Thrombocytopenia, AKI
1413
Wegener's causes rapidly progressive
Crescentic GN
1414
Microangiopathic Hemolytic Anemia, Thrombocytopenia, AKI
Hemolytic Uremic Syndrome is triad of
1415
3 significant causes of endothelial damage
E Coli toxin (auto-Ab's), Chemo, Radiation
1416
Fibrinoid Necrosis and Thrombosis in Scleroderma
Common
1417
Causes of Thrombotic Microangiopathy includes ___ in children and ___ in adults
Hemolytic Uremic Syndrome, TTP
1418
What has prolonged PT and PTT: TMA or DIC
DIC - Consumptive coagulopathy
1419
2 features shared between TMA and DIC
Thrombocytopenia and Microangiopathic Hemolytic Anemia
1420
PR3-ANCA is specific for Granulomatosis w Polyangiitis
True, 95%
1421
Primary target in small vessel vasculitis
Endothelial cells
1422
Effect of PAN on kidneys
Not GN - Macroscopic ischemia and infarction
1423
Which arteries are affected by intimal and medial proliferatioin scleroderma renal crisis
Arcuate
1424
Small vessel vasculitis involving glomeruli usually causes
Pauci-immune Crescentic GN
1425
Who is usually affected by HUS
Small children under 5 years
1426
Small vessel vasculitis causes
Focal necrotizing lesions with crescents, active urinary sediment, Rapid progression of kidney failure
1427
4 most common inflammatory manifestations of SLE
Non-erosive Synovitis (90), Skin lesions (85), Nephritis (50), Cerebritis (50)
1428
2 major features of TTP
MHA, Thrombocytopenia
1429
Thrombotic Microangiopathy must be differentiated from
DIC
1430
Wire loop lesions are inidicative of
Active disease
1431
What do ANCA's do to their targets in granulocytes
Activate neutrophils, which then adhere to endothelial cells; Also prevent inactivation of the targeted granulocyte componens (PR3, MPO, etc)
1432
What does factor H regulate
Complement
1433
Which part of glomerulus is affected in SLE
All 3 locations
1434
ANCA cause
Endothelial Cell injury in Glomeruli and Blood Vessels
1435
Segmental Transmural Necrotizing Vasculitis
PAN
1436
In about 10% of cases, HUS in children is due to
Inherited mutation that inactivates Factor H
1437
P-ANCA may be positive in up to ___% of patients with Anti-GBM disease
30%
1438
5 features of TTP
2 major: MHA, Thrombocytopenia; Others: Neurologic dysfunction, renal dysfunction, fever
1439
What causes wire loops in SLE
Confluent circumferential Subendothelial deposits cause the glomerular capillary walls to be thickened
1440
3 Clinical Clues to ATN
(1) Muddy brown granular casts; (2) Urine Na > 20; (3) Fractional excretion of Na > 1%
1441
Urine in Acute Interstitial Nephritis
Pyuria +/- eosinophils
1442
Effect of Aminoglycosides on Kidney
Inhibits normal lysosomal function, accumulates in PT cells
1443
What can you do in suspected HRS to rule out simple pre-renal condition
Trial of volume (usually Albumin) infusion
1444
Why is urine Na high in ATN
Necrotic tubular cells can't reabsorb Na so excreted
1445
Symptoms of Acute Interstitial Nephritis in most patients now
Only renal dysfunction
1446
2 Therapeutic agents that cause Pre-Renal AKI
NSAIDs, ACEi's
1447
What does survival in Hepatorenal Syndrome depend on
Liver transplant
1448
How to avoid Contrast Nephropathy
Avoid closely spaced studies
1449
Acute Interstitial Nephritis is most commonly caused by
Beta Lactam Abx, NSAIDs
1450
Histology of ATN
Tubular necrosis with denuding of renal tubular epithelial cells; Occlusion of tubular lumens with cells/casts
1451
(1) Muddy brown granular casts; (2) Urine Na > 20; (3) Fractional excretion of Na > 1%
3 Clinical Clues to ATN
1452
Most common cause of Post-renal AKI
Prostate disease
1453
Worsening renal failure in setting of cirrhosis =
Hepatorenal syndrome
1454
Must rule out what else to conclude HRS
NSAIDs, Nephrotoxic drugs, Contrast
1455
BP and ECV in Hepatorenal Syndrome
Decrease BP despite incr ECFV (decr ECV)
1456
Why is Uosm high in Pre-Renal and Normal in ATN
High Aldo in Pre-Renal; In ATN, necrotic cells can't dilute or concentrate so same as blood
1457
BUN/Cr in Pre-Renal vs ATN
>20:1 in Pre-Renal; 10-15:1 in ATN
1458
Most common class of AKI? Second?
55% Pre-renal, 40% intrinsic
1459
Acute Kidney Injury is essentially
Impairment of GFR
1460
Calyce visible on renal US means
Obstruction of outflow
1461
2 Aminoglycosides
Gentamycin, Topomycin
1462
How do contrast agents cause AKI
Direct vasoconstrictive effects on arterioles; Also directly toxic
1463
Main 2 Causes of ATN
Ischemic injury; Toxic injury from contrast or meds
1464
Usual symptoms of AKI
Usually asymptomatic and discovered on routine labs
1465
Why do ACEi's cause Pre-Renal AKI
Inhibit Ang2 which selectively constricts efferent arterioles
1466
Oliguria is defined as
Less than 400mL / 24 hours
1467
Management of Ischemic ATN
Treat underlying cause - Restore perfusion
1468
FENa in Pre-Renal vs ATN
Less 1% in Pre-Renal; Greater than 1% in ATN
1469
Muddy Brown Casts =
ATN
1470
Timeframe of AKI
Rapid deterioration of kidney function < 1 month
1471
Hepatorenal syndrome results from what liver disease
Cirrhosis
1472
UNa+ in Pre-Renal vs ATN
Less than 20 mEq/L in Pre-Renal; Greater than 25 mEq/L in ATN
1473
How do you prevent Aminoglycoside toxicity
Once daily dosing; Minimize duration of tx
1474
___ can cause form of pre-renal AKI in patients with Bilateral RAS
ACEi's and ARB's
1475
Impairment of GFR (AKI) leads to
Elevation of BUN/Creatinine, Accumulation of substances/drugs normally excreted by kidney
1476
Inhibits normal lysosomal function in kidney
Aminoglycosides
1477
3 Specific Types of Pre-Renal AKI
(1) Hepatorenal Syndrome; (2) RAS and Ang2 blockers/ACEi's; (3) Other drugs that impair autoregulation (NSAIDs)
1478
2 causes of Post-renal AKI other than prostate
Malignancies, Neurogenic bladder
1479
ACEi's and ARB's can cause ___ in patients with Bilateral RAS
Pre-Renal AKI
1480
Decreased levels or inhibition of Ang2 impairs renal ____
Auto-Regulation (constriction of efferent arterioles in RAS)
1481
Urine [Na] and Osm in Pre-Renal AKI
Very low Na (Aldosterone overactive), Very high osmolarity (ADH overactive)
1482
Dx of Post-renal AKI
Foley catheter, US
1483
Urine Na in HRS
Very low (Aldosterone)
1484
Uosm in Pre-Renal vs ATN
>500 mOsm/kg vs 300-350 mOsm/kg
1485
As BP falls, kidneys are able to maintain BP well, unless __
Ang2 blocker interferes with Efferent Arteriole vasoconstriction (impaired autoregulation)
1486
Urine output in AKI
Sometime decr, but not always
1487
Hyaline casts are seen in what type of kidney injury
Pre-renal AKI
1488
Urinarlysis in Hepatorenal Syndrome
Usually normal
1489
Most accurate test for Pre-Renal AKI
Fractional excretion of Na - If less than 1%, suggestive of pre-renal
1490
U/A in Pre-Renal vs ATN
Hyaline Casts vs Granular Casts
1491
Creatinine change criteria for AKI
Greater than 0.5mg/dL incr or incr of 50% over baseline
1492
Most important cause of Intra-renal AKI discussed
ATN
1493
Pre-Renal AKI is due to insufficiency of
Renal perfusion
1494
Urinalysis in Post-renal AKI
Unremarkable
1495
How do NSAIDS cause Pre-Renal AKI
Block PG's that dilate the afferent arterioles
1496
How does hypocalcemia affect Vit D
Stimulates PTH --> Stimulates 1a-Hydroxylase -> Incr 1,25 production by kidneys
1497
4 Major Consequences of CKD-MBD
Renal Osteodystrophy, Fractures, Calcification, CV Disease
1498
FGF-23 directly inhibits
1a-Hydroxylase
1499
How does VDR activation affect PTH levels
Higher activation = Lower PTH
1500
Hereditary Tumoral Calcinosis is disorder of
FGF23 Deficiency
1501
Why are FGF19, 21, and 23 unique
Don't need Heparin, so can circulate and act as endocrine factors (rather than paracrine)
1502
Disorder of FGF23 excess is called
Hereditary/Acquired Hypo-Phosphatemic Rickets
1503
Change in serum calcium in CKD
Decreases
1504
Hereditary/Acquired Hypo-Phosphatemic Rickets is a disorder of
FGF23 Excess
1505
First, or one of the first, markers in CKD
FGF-23
1506
Pitfalls of Serum Ca2+ measurement
Assay measures total, but 40% of Ca is bound to albumin, and only free and ionized Ca is biologically active
1507
Bones in FGF23 excess vs deficiency
Rickets/Osteomalacia in excess; Hyperosteosis in deficiency
1508
Effect of FGF-23 on Heart
LV Hypertrophy
1509
How does bone metabolism affect FGF-23
Osteocytes and osteoblasts secrete FGF-23
1510
FGF-23 is involved in
Phosphate and Vit D homeostasis
1511
FGF-23 correlation with Phosphorus in Norma vs CKD/ESRD
in normal, higher fgf-23 = lower PO4; in ckd, higher fgf-23 = higher PO4
1512
How does 1,25(OH)2 affect FGF-23
Increase FGF-23
1513
Similar to Phosphate, extracellular pool is only ____ proportion of total body Ca
Small
1514
Consequences of Hypercalcemia
CV and Soft Tissue Calcification
1515
Diffuse calcification of tunica media causes what pathophysiology
High pulse wave velocity
1516
T/F: Tubular reabsorption of Phosphate is unsaturable
FALSE
1517
T/F: CVD mortality rates are 5 times higher in Stage 5 CKD patients than general population
False, 10-20 times higher
1518
1,25(OH)2 in Vit D Deficiency: normal kidney vs CKD
Normal or increase in normal kidney patient; Low in CKD patient
1519
Urinary Ca excretion in CKD
Marked decr in Ca excretion with advancing states of CKD
1520
Key regulator of Ca absorption
Active Vit D
1521
Clinical features of FGF23 excess
Low serum Phosphate, Aberrant Vit D, Rickets/Osteomalacia
1522
Phosphate in FGF23 excess vs deficiency
Low in excess, high in deficiency
1523
How does PTH affect Vit D
Incr 1a-hydroxylation of Vit D
1524
Main pathophysiology seen in patients on dialysis
Increased pulse wave velocity
1525
The higher the level of Ca in dialysis patients, the higher the
Mortality rate
1526
Most patients with normal kidney fxn who are vit d deficient have what levels of 1,25
Normal or increased (paradoxically, because missing precursor
1527
What is consequence of maintaining 1,25(OH)2 levels with Vit D deficiency
Hypophosphatemia (Osteomalacia)
1528
Consequence of Hypocalcemia
Increased neuromuscular excitability
1529
At what GFR will you see major changes in Phosphorus and Calcium
Not until less than 30 (GFR)
1530
Ratio of Fecal to Renal loss for Calcium
700 mg/dL to 300 mg/dL
1531
Effect of FGF-23 on RAAS, Klotho, Inflammation
Inc RAAS, Dec Klotho, Inc Inflammation
1532
How does Calcitrol aka 1,25(OH)2 Vit D affect transcription
Binds with VDR nuclear receptor in cytoplasm, dimerizes with RXR, and both bind Vit D response element
1533
Klotho is necessary for
FGF23
1534
Effect of FGF23 on PTH, 1a-Hydroxylase
Inhibits both
1535
In Vit D deficiency with CKD, PTH cannot stimulate ___, leading to def in ____
1a-Hydroxylase, deficiency in 1,25(OH)2
1536
High ___ mileu may potentiate Calcium fluxes in CKD
phosphorus
1537
Main reason hyperphosphatemia is detrimental
Phenotypically, vascular SM cells turn to bone
1538
2 factors that play a role in calcium absorption
Amount of intake, amoung of 1,25(OH)2 Vit D
1539
Does Ca2+ level affect mortality
Yes, higher Ca2+ means much higher mortality rate
1540
Clinical features of FGF23 deficiency
Hyperphosphatemia, Elevated Calcitrol, Soft tissue calcifications, Hyperosteosis
1541
Ratio of Fecal Loss vs Urine Loss of Phosphorus
500 to 900
1542
What percent of phosphorus is in ECV? Soft tissue? Bone?
1%, 14%, 85%
1543
T/F: Albumin-adjusted serum Ca levels correlate well with ionized Ca in CDK and ESRD
False, correlate poorly - don't adjust for Albumin
1544
Normal Phosp plasma conc.
3-4.5 mg/dL
1545
Serum phosphorus in stage 5 CKD
Predictably elevated
1546
Calcium in what state is actually active
Free (unbound to Albumin) and ionized
1547
With GFR > 40, TmPhosphate ___ with GFR
TmP Varies proportionately with GFR
1548
Effect of Vit D on PO4
Incr reabsorption in gut; Decr reabsorption in kidney
1549
How does primary decr of Ca affect PTH
Increases PTH
1550
Calcium balance in CKD
If diet is low in calcium, neutral balance; If diet is high in calcium, more positive balance than controls (they are more sensitive)
1551
How does Ca affect PTH
Hypocalcemia stimulates PTH production
1552
Cofactor for FGFs (except 19, 21, 23)
Heparin
1553
Effect of PTH on Bone
Increase reabsorption --> Incr Ca and PO4
1554
Vit D deficiency patients with normal kidney function
Normal 1,25(OH)2 but at expense of Hypophosphatemia (osteomalacia)
1555
PO4 in Vit D deficiency: normal kidney vs CKD
Low in normal patient, high in CKD patient
1556
How and where is Vitamin D3 converted to 25(OH)
In liver by 25-hydroxylase
1557
Change in serum phosphorus in CKD
Increases
1558
First, or one of the first, regulators when GFR lost
FGF-23
1559
Phosphate and Vit D in secondary HPT in CKD
Vitamin D deficiency --> Phosphate retention (lower capacity to secrete Phosphate in kidney)
1560
With GFR < 40, TmPhosphate ____
Further decreases, but decrease is less than decrease in GFR = Hyperphosphatemia ensues
1561
Effect of Calcitrol supplementation on longevity
Improves
1562
Calcification seen in CKD vs general population
Medial vs Intimal
1563
Vit D in FGF23 excess vs deficiency
Low in excess, high in deficiency
1564
FGF-23 levels in ESRD
Markedly elevated
1565
If you try to explain bone mineral metabolism with PTH, you run into trouble with
Phosphorus - PTH both increases and decreases PO4
1566
Effect of PTH on PO4
Incr thru bone and gut via Vit D, Decr reabsorption in kidney (opposing effects)
1567
Dialysis greatly increases deposits of what in coronary arteries
Calcium
1568
Percent of Phosph Filtered Load that is reabsorbed? What contributes to most of this reabsorption?
80-97%, 80% of this in PT
1569
Why do you get Hyperphosphatemia with low GFR
With GFR less than 40, TmPO4 further decreases, but decrease is less than decrease in GFR
1570
Hyperphosphatemia initiates a cascade of events that results in
Calcification of vascular SM cells
1571
How does PTH affect gut absorption
Enhances absorption of Ca and PO4 thru increased Vit D
1572
Association of serum phosphorus to mortality in dialysis patients
Higher mortality with higher phosphate levels (and very low levels)
1573
FGF vs PTH as marker for PTH
Both good, but FGF-23 earlier
1574
PO4, FGF-23, ALP, PTH in CKD, MBD
All increase
1575
Disorder of FGF23 deficiency is called
Hereditary Tumoral Calcinosis
1576
How and where is 25(OH) Vit D converted to 1,25(OH)2 Vit D
By 1a-Hydroxylase most in tissues but also in kidney
1577
Consequences of increased pulse wave velocity due to dialysis calcification
Inc afterload -> LVH; Decr coronary perfusion pressure; Incr Myocardial O2 demand; Incr endothelial dysfunction and atherogenesis
1578
Phosphate imbalance with low GFR
Hyperphosphatemia
1579
Gordon Syndrome is characterized by
Salt-sensitive HTN, HyperK, Metabolic Acidosis
1580
Individuals from INTERSALT had higher ___ compared to rural populations
Average systolic and Diastolic BP
1581
Tx for Genetic PseudoHypoAldosteronism
Triamterene Amiloride
1582
Activating WNK-1 and Inactivating WNK-4 both cause
Increased activity of NaCl channel and incr Na reabsoprtion (Gordon's)
1583
Gene mutation leading to Aldosterone Synthetase responsive to ACTH
Glucocorticoid Remediable Aldosteronism
1584
Dry HTN
Essential with High Renin
1585
Gordon Syndrome is due to
Constitutive activation of Thiazide-Sensitive NaCl channels in DCT
1586
% of HTN and Normotensive individuals with salt sensitivity
50 and 26
1587
Inability of kidneys to appropriately excrete Na load
Guyton's theory
1588
Pressure-Natriuresis: ___ is mediator
Changes in interstitial medullary pressure
1589
Increase in CO in Essential HTN
does not persist
1590
All forms of Secondary HTN are characterized by
Salt-sensitive HTN
1591
Ignores role of ANS: Fails to explain incr BP in pre-HTN, where CO incr is mainly driven by SNS activaiton
Cons of Guyton's Theory
1592
Mechanisms of Salt's role in HTN
Dec Na excretion, Incr SNS activity, Incr activity of Na-H exchanger, Incr Ca in vascular SM cells
1593
Tx for Liddle's
Triamterene or Amiloride
1594
Does salt-sensitivity change with age
Yes, increases
1595
Renin and Aldosterone in Secondary HTN
Low Renin and Aldosterone, except Aldosterone Excess obv
1596
Liddle's disease is due to
Activating ENaC mutation
1597
Psuedohypoaldosteronism Type 2 is aka
Gordon Syndrome
1598
Cause of Liddle's Syndrome
Constitutive activation of ENaC in DT due to mutaiton in subunit
1599
Laragh's Hypothesis
Some nephron's are ischemic and produce high renin, while others are not but will have impaired natriuresis from AT2 - Total PRA is diluted/normal
1600
Decr Na excretion leading to Incr CO is corrected by autoregulation at expense of
Incr SVR and BP
1601
Causes of PseudoHypoAldosteronism (non-Liddle's)
11B-HSD-2 Defiency of Inhibition
1602
Action of 11B-HSD-2
Breaks down Cortisol
1603
Volume and Renin in Goldblatt Model 1
Renin is high, but volume is normal b/c contralateral kidney is able to excrete excess Na
1604
Change in Pressure-Natriuresis curve with salt-sensivity
Decrease in slope
1605
Worsening condition after ACEi =
Highly suggestive of Bilteral RAS
1606
How does Pseudohypoaldosteronism cause Hypokalemia
Incr Na reabsorption in CD creates favorable gradient for K secretion
1607
Decrased NaCl delivery to MD increases ___ production
NO and PG
1608
Ouabain is activated by
Incr PV
1609
What channel is upregulated in Aldosterone excess that contributes to HTN
ENaC channel reabsorbs Na in CD
1610
Channel upregulated in Cushing's that contributes to BP increase
ENaC channel reabsorbs Na in CD
1611
Goldblatt Model 1
Unilateral RAS w/ 2 normal kidneys - Incr SVR and Right shift in pressure natriuresis - Normal volume
1612
Role of Genetics in HTN
70-80% of individuals have positive family history
1613
Inc Pre-Load can be due to
Incr Venous Tone or Incr Volume (and therefore total Na)
1614
What inhibits 11B-HSD-2
Chronic licorice ingestion (candies, chewing tobacco)
1615
ACEi's in Goldblatt Model 1
Reduce BP b/c stenotic kidney is secreting renin
1616
ACEi's in Goldblatt Model 2
Will not help - In fact, they'll reduce GFR - RAAS necessary to maintain GFR in this scenario
1617
As CKD progresses, revalance of HTN ___
rises
1618
Renin levels in Essential HTN
20% high, 30% low, 50% normal
1619
Brenner's Hypothesis
Reduction in Nephron Mass
1620
MAP = CO x SVR =
DBP + 1/3(SBP-DBP)
1621
Guyton's theory
Inability of kidneys to appropriately excrete Na load
1622
Effect of Ouabain on SVR and Venous Tone
Increases SVR and Venous Tone
1623
Pressure-Natriuresis: Changes in Na excretion occur without
changes in GFR
1624
Deficiency in 11B-HSD-2 leads to excess
Cortisol
1625
Activating ENaC mutation
Liddle's disease is due to
1626
2 mutations that cause Gordon's
Activation of WNK-1, Inactivaiton of WNK-4
1627
Volume and Renin in Goldblatt Model 2
Both high
1628
Infusion of Saline in normal kidney patient vs anephric
Small changes of BP in normal; rapid rise in anephric
1629
Goldblatt Model 2
Biltateral RAS - No off-setting pressure natriuresis
1630
Reduction in Nephron Mass --> ___ --> ___
Systemic/Glomerular HTN --> Acquired Glomerular Sclerosis
1631
Cause of Hyperkalemia in Gordon's
Reduced distal Na delivery, so decreased K secretion
1632
Ouabain acts on
Na/K ATPase
1633
No salt, no ___, even with ____
No salt, no HTN, even with aging
1634
Which activate and which inhibit Renin: B1 rec, Adenosin2 rec, Prostaglandin rec
B1 and PG activate, Adenosin2 inhibits
1635
Age of onset for primary HTN
40s and 50s
1636
Aloows for normal BV despite elevated pressure
Pros of Guyton's Theory
1637
Pressure-Natriuresis: ___ is the principal site
Outer Medulla (TALH)
1638
What is necessary to maintain GFR in Goldblatt Model 2
RAAS, so ACEi's are contraindicated
1639
Mechanism of Volume Expansion in Glucocorticoid Excess (Cushing's)
Cortisol excess activates ENaC (same as aldosterone)
1640
Most common causes of RAS
Atherosclerosis (85%), Fibromuscular Dysplasia (15%)
1641
K and Acid-Base in Secondary HTN
All associated with Hypokalemia and Metabolic Alkalosis except Gordon Sydnrome
1642
Inactivating mutations in 11B-HSD-2 gene
Apparent Mineralocorticoid Excess is due to
1643
2 factors that activate renin release from JGA in response to Renal hypoperfusion
Decr afferent artiolar stretch, Decr NaCl delivery to Macula Densa
1644
Wet HTN
Essential with Low Renin
1645
T/F: We are all salt-sensitive to some degree
FALSE
1646
SV can be increased by
Incr in Pre-Load or Contractility
1647
Pros of Guyton's Theory
Aloows for normal BV despite elevated pressure
1648
What normally degrades Cortisol
11B-HSD2
1649
Is peripheral edema common in essential HTN
No
1650
Does Adenosine vasoconstrict or dilate
Vasoconstrict
1651
Apparent Mineralocorticoid Excess is due to
Inactivating mutations in 11B-HSD-2 gene
1652
Prevalence of RAS is higher with
age, DM, PVD, DBP >125
1653
Gordon's Syndrome mimics
Gitelman's
1654
How does PseudoHypoAldosteronism cause Metabolic Alkalosis
Hypokalemia causes shift of H+ into tubular cells and then secretion into lumen; Also incr H+ secretion by H pump
1655
What is Pressure Natriuresis
When perfusion press incr., renal Na output incr and ECFV and BV contract to return MAP to baseline
1656
Increase NaCl delivery to MD increases ___ production
Adenosine
1657
Local factor autoregulation is mediated primarily by
NO
1658
Tx of Gordon's Syndrome
Thiazide Diuretics
1659
Cons of Guyton's Theory
Ignores role of ANS: Fails to explain incr BP in pre-HTN, where CO incr is mainly driven by SNS activaiton
1660
What % loss of nephron mass results in increase risk of HTN, Proteinuria
50%
1661
Stage 5 CKD
GFR <15 or Dialysis
1662
Diuretic used for BP
Thiazide
1663
Most important element to determine glomerular vs tubular disease
Urinalysis
1664
Net result of GI effects of Renal Insufficiency
Protein Calorie Malnutrition
1665
ACEi's and ARB's reduce systemic pressure and are unique in
reducing glomerular capillary pressure
1666
Nervous system changes in early to moderate renal insufficiency
Intellectual function, particularly concentrating
1667
Common manifestation of overt encephalopathy
Asterixis
1668
Pressure Natriuresis curve for Essential HTN
Shifted Right and Decreased Slope
1669
How does muscle mass affect Screatinine readings
If higher muscle mass, serum creatinine will normally be higher and will under-estimate GFR
1670
Most common cause of eosinophils in urine
Allergic Interstitial Nephritis
1671
Endocrine abnormalities with advanced renal failure
Fasting Hypoglycemia
1672
3(4) Factors suggesting Tubular etiology over Glomerular
Absence of heavy proteinuira; Inability to dilute or concentrate urine (Gsp 1.010); Hyperkalemia and Metabolic Acidosis out of proportion to degree of renal insufficiency
1673
Early changes in Diabetic Nephropathy
Hyperfiltration resulting in glomerular capillary HTN and Glomerular Hypertrophy
1674
3 Disease Dependent mechanisms of Nephron Injury
Vascular, Glomerular, Tubular
1675
HTN promotes nephron loss in which types of renal diseases
All: Tubular, Glomerular, Vascular
1676
When do you not give Epo
Iron deficient
1677
Most life threatening electrolyte abnormality
Severe Hypokalemia
1678
First abnormality in Diabetic Nephropathy
Microalbuminuria
1679
Why Anemia in advanced renal failure
Diminished EPO production
1680
While creatinine conc increases as a function of GFR, BUN increases as function of
GFR and Urine Flow Rate
1681
What has been shown to preserve renal fxn in both proteinuric and non-proteinuric renal diseases
Maintenance of normal BP with anti-hypertensives and dietary Na restriction
1682
Anemia in CKD occurs at what GFR
30% of normal
1683
Main thing to control in chronic kidney disease
BP
1684
Symptoms of chronic kidney disease
Most commonly asymptomatic
1685
Most common cause of Advanced Kidney Disease
DM
1686
What increases after 5/6 nephrectomy
SNGFR, Glomerular Pressure, Glomerular Volume, Urine Albumin --> Sclerosis
1687
Result of increased TGF-beta by RAAS activation
Fibrosis
1688
4 common symptoms of chronic kidney disease
Peripheral Neuropathy, Bone changes (high PTH), Small echogenic kidneys, Waxy casts
1689
How does protein restriction affect GFR
Protein intake normally raises it transiently
1690
Greater than 50% loss of nephron mass results in dose dependent increase in risk of
HTN, Protein (focal segmental glomerulosclerosis)
1691
CKD is best throught of as
Loss of functioning nephrons
1692
How does GFR affect 1a-Hydroxylase and 1,25(OH)2
Decr GFR -> Decr 1a-Hydroxylase -> Decr 1,25(OH)2
1693
Type of Anemia in CKD (PBS findings)
Normocytic, Normochromic with Burr Cells
1694
Can Nomograms be used for Acute Renal Failure
No, must be steady state
1695
Histology of Diabetic Nephropathy
Increased mesangial matrix, Glomerular Collapse, Glomerulosclerosis
1696
GI effects of Renal Insufficiency
Decreased appetite, Nausea (gastroparesis, happens on empty stomach), Vomitting --> Net result is protein calorie malnutrition
1697
Pressure Natriuresis curve for Loss of Renal Mass
Significantly decreased slope, not shifted right
1698
Chronic Renal Insufficiency equals a reduce
number of normally functioning nephrons
1699
Stage 2 CDK
60-89
1700
Pressure Natriuresis curve for Aldosterone-Stimulated Kidneys
Very decreased slope, not shifted right
1701
What decreases after 5/6 nephrectomy
Number of Glomerular Epithelial cells, Kf
1702
Can nomograms be used for Chronic Renal Insufficiency
Yes, not acute
1703
Prevalance of Nephropathy in DM
30-40% of type 1, unknown in type 2
1704
Why Fasting Hypoglycemia in advanced renal failure
Decreased Insulin degradation, Decreased gluconeogenesis by kidney
1705
Which GFR formula is most commonly reported in hospital labs
MDRD equation
1706
What do ACEi's and ARB's reduce that make them superior to other anti-HTN in CKD
Glomerular capillary pressure and Proteinuria
1707
Pros and Cons of Protein Restriction
Reduces workload of glomerulus, but poor adherence and promotes malnutrition
1708
Allergic Interstitial Nephritis is characterized by
Presence of Sterile Pyuria
1709
Late Chronic Renal Failure is associated with what CV changes
Marked Anemia, Volume Overload -> CHF, Pericarditis
1710
Nomograms are useful only in
Steady State Conditions - Chronic Renal Insufficiency
1711
Volume status in essential HTN in advanced CKD patients
Normal volume status until GFR becomes depressed
1712
Renal response to nephron loss
Compensatory Glomerular Hypertophy and Hyperfiltration
1713
What causes low Vit D in renal insufficiency
Decr GFR and HyperPhosphatemia -> Decr 1a-Hydroxylase -> Decr 1,25(OH)2
1714
Primary route for excretion of PO4
Kidney
1715
What is an echogenic kidney
White on US - likely chronic
1716
Will serum creatinine over or under-estimate true GFR
OVER
1717
__ in remaining nephrons may mask the presence of nephron loss
Increased filtration
1718
Term used to describe signs and symptoms associated with advanced renal failure
Uremia
1719
What percent of patients with Advanced CKD have HTN
85-90%
1720
Nervous system changes: More severe failure can lead to
Overt encephalopathy, often manifested by Asterixis; Peripheral Neuropathy
1721
In proteinuric diseases, which class of drugs has been shown to have a selective advantage over other anti-HTN
ACEi's and ARB's
1722
Last electrolyte for which homeostasis is lost
K
1723
Signs and Symptoms of Uremia
Nausea, Vomiting, Anorexia, Confusion, Encephalopathy, The Flap
1724
3 Factors suggesting Glomerular over Tubular
2+ or greater proteinuria; RBC casts; Gsp > 1.015
1725
Diuretic used for advanced kidney disease
Loop
1726
Adverse effects of Hyperphosphatemia
(1) Inhibit 1a-Hydroxylase; (2) Enhance PTH directly; (3) Metastatic Calcification
1727
Does CKD progress even if initial injuring stimulus is removed?
Yes
1728
What percent of HTN in advanced CKD patients is volume driven
80%
1729
3 Consequences in Trade-Off Hypothesis
Secondary HyperParathyroidism (Ca, PO4), Hypertension (Na), Hyperaldosteronism and HTN (K)
1730
RBC Casts =
Glomerular etiology
1731
Urine output in CDK
Still have urine until very end (surprisingly)
1732
What is Uremia
Term used to describe signs and symptoms associated with advanced renal failure
1733
Acid Base dysfunction in CKD and why
Decr ability to excrete acid -> Decr new bicarb -> Metabolic Acidosis with Normal AG
1734
Which anti-HTN drugs reduce glomerular capillary pressure
ACEi's and ARB's
1735
Renal H+ secretion into urine is synonymous with
Addition of new bicarb into blood
1736
When are creatinine clearance and nomograms useless
When Creatinine is changing
1737
Stage 3 CKD
GFR 30-59
1738
Early Chronic Renal Failure is associated with what cardiac changes
HTN --> LV Hypertrophy
1739
Maintenance of normal BP has shown to preserve renal fxn in which class of renal diseases
Both Proteinuric and Non-Proteinuric
1740
2 main signs of chronic kidney disease
Small, shrunken kidneys; Waxy casts
1741
What causes >10:1 BUN:Creatine ratio
Pre-renal Azotemia, Dehydration -> Decr urine flow rate -> Decr excretion of Urea -> Disproportionate increase in BUN
1742
Adverse effects of RAAS other than Na retention and systemic vasoconstriction
Glomerular HTN (efferent art constriction), Increased release of TGF-beta --> Fibrosis
1743
Which organ systems are affected by chronic renal insufficiency
Virtually all
1744
Stage 4 CKD
GFR 15-29
1745
Do damaged nephrons function appropriately?
Generally, yes - therefore, loss of renal homeostasis is due to decreased numer
1746
Creatinine has to be ___ to use to estimate GFR
Stable, steady state
1747
How does GFR affect Ca absorption in gut
Decr GFR -> Decr 1a-Hydroxylase -> Decr 1,25(OH)2 -> Decr Ca absorption
1748
Patients with __ should be in the highest risk group fro CVD, irrespective of ___
CDK, irrespective of traditional CVD risk factors
1749
Uremia is 100% fatal unless
Reversible factors found that can improve GFR; Renal replacement tx
1750
One of the first things that will increase in blood with renal insufficiency
Phosphorus
1751
Best Anti-HTN's to use in CKD
ACEi's and ARB's
1752
Which anti-HTN decrease proteinuria more than others
ACEi's and ARB's
1753
Primary lesions in Arist Acid nephropathy are likely centered in
vessel walls --> Ischemia and interstitial fibrosis
1754
PT dysfunction is manifested by
Decr reabsorption of Glucose, AA's, etc
1755
Urine Sediment in Pre-Renal AKI vs ATN
Hyaline casts vs Muddy Brown Coarse Granular Casts
1756
Earliest functional defect in Hypercalcemic Nephropathy is
Inability to concentrate the urine
1757
Lithium typically injures what part of nephron and thus leads to what
CD --> Nephrogenic DI
1758
Mechanism of Arist Acid Nephropathy
DNA adducts
1759
Goal of interstitial disease treatment is to
not let interstitial fibrosis occur
1760
Type of immunity that plays predominant role in Acute IN
Cell-mediated --> Sometimes form granulomas
1761
Type of immunity that plays role in Methicillin-induced AIN
Ab-mediated plays role in addition to Cell-mediated
1762
As opposed to Analgesic Abuse Nephropathy, Aristolochich Acid Nephropathy is localized to
Cortex
1763
Most common genetic kidney disease
PCKD
1764
All the heavy metals have been associated with __ injury
tubular
1765
AKI is a rise in serum creatinine of at least __ over a __ period and/or a rise of ___times baseline within previous ___ days
0.3 mg/dL over 48 hour period; >1.5 times baseline within previous 7 days
1766
__ gets lower with larger volume in PCKD
GFR
1767
Time frame of Acute Drug-Induced IN after use of drug
15 days
1768
Urinalysis of Contrast-induced Nephropathy
Renal Tubular Epithelial Cells and Coarse Granular Casts; No pyuria because non-inflammatory process (nephropathy)
1769
Most common process behind AIN after NSAIDs
Viral infections
1770
4 Causes of Papillary Necrosis
DM, Analgesic Nephropathy, Sickle-Cell, Obstruction
1771
Origin of uric acid
Breakdown of DNA
1772
Urinalysis in PCKD
Bland b/c no glomerular disease
1773
Analgesic Abuse Nephropathy initially was reported with use of
Phenacetin
1774
DT dysfunction is manfiest by
Decr reabsorption of Na, K, H
1775
Waxy casts in interstitial disease tell you what
Chronic
1776
At what age are cysts visible in PCKD
20-30 years
1777
Description of Arist Acid Nephropathy
Chornic, irreversible, scarring, non-inflammatory
1778
Clinical presentation of AIN
Sudden renal insufficiency, fever, rash, flank pain
1779
What cells get damaged in kidney in Hypercalcemia Nephropathy
Tubular epithelial cells
1780
Histology of NSAID-assoicated IN
Minimal Change Disease
1781
Prognosis of NSAID-associated IN
Usually improves with discontinuation
1782
Elevated CPK, myoglobin in urine
Rhabdomyolysis (statins, trauma)
1783
PCKD can be thought of as a
Ciliopathy (genes mutated encode proteins within primary cilia of renal tubular cells)
1784
Is Arist Acid Nephropathy acute or chronic
Chronic, irreversible, scarring, non-inflammatory
1785
2 methods of injury by contrast
Vasoconstriction, Direct nephrotoxicity
1786
Urine Osmolarity in Pre-Renal AKI vs ATN
>500 vs 300
1787
What does urine specific gravity of 1.010 mean
Can't concentrate or dilute --> urine osmolarity is same as plasma
1788
What cytokine plays a critical role in Acute IN
TGF-beta
1789
Setting in which Acute Phosphate Nephropathy usually occures
High doses of oral phosphate for colonoscopy
1790
Cause of Balkan Nephropathy
Aristolochic Acid Nephropathy
1791
Prolonged, severe Hypercalcemia leads to
Nephrogenic DI - Can't concentrate urine
1792
What indicates chronic interstitial disease? What indicates allergic?
Waxy casts if chronic. Eo's if allergic.
1793
Most sensitive indication of PT dysfunction
Glucose in urine with normal blood sugar
1794
Histology of Uric Acid Nephropathy
Uric Acid crystals in tubules
1795
Most frequent cause of Interstitial Nephritis
NSAID-associated
1796
Anemia in Glomerular disease vs Tubular
Worse in tubular because tubule produce the EPO
1797
Triad of Acute Drug-Induced Interstitial Nephritis
Fever, Eosinophilia, Rash
1798
Inflammatory infiltrate in Arist Acid Nephropathy
Minimal, more direct injury
1799
Urine Na concentration in Pre-renal AKI vs ATN
< 20 vs >40
1800
Unusual finding/symptom of NSAID-associated IN
Nephrotic Range proteinuria
1801
Causes of Hyperkalemia and RTA in Interstitial Diseas
Impaired K secretion in cortical CD, Impaired H+ secretion
1802
Timeline of clinical presentation after starting drug that causes AIN
within 3 weeks
1803
In Analgesic Abuse Nephropathy, drug accumulates in ___
Renal Medullary Interstitium
1804
Medullary dysfunction is manifested by
Impaired urine concentrating ability
1805
__ stones are not visible w/ plain radiographs
Uric Acid Stones
1806
Clinical manifestation of Aminoglycoside Nephrotoxicity
Progressive incr serum creatinine, Renal K and Mg wasting, Renal Glucosuria
1807
Proteinuria and Pyuria in Interstitial Disease
Minimal proteinuria, Sterile pyuria
1808
Papillary dysfunctin is manifested by
Impaired urine concentrating ability
1809
Aminoglycosides injure what part of nephrone
PT
1810
Hallmark in urinalysis of Interstitial Disease
Concentrating defect --> Sp Gravity of 1.010 (urine osmolarity of 300 mOsm/kg)
1811
Time course of papillary necrosis from DM
10 years
1812
Plasma BUN/Creatinine Ratio in Pre-Renal AKI vs ATN
>20 vs
1813
Signs of tubular function abnormality w/ interstitial disease
GFR, Anemia, Dehydration, HyperK, RTA
1814
Exposure to Arist Acid
Soil
1815
Analgesic Abuse Nephropathy may progress to
Papillary Necrosis
1816
Urine Specific Gravity in Pre-Renal AKI vs ATN
> 1.018 (high) vs 1.010 (low)
1817
Chinese Herb Nephropathy is due to
Rapid IN from Aristolochic Acid
1818
Heavy metals typically injure what part of nephron
Proximal Tubule
1819
What types of patients are likely to get contrast nephropathy
Preexisting renal insuff; DM; Volume depleted
1820
2 causes of free iron in urine that damages tubules
Rhabdomyolysis, Intravascular Hemolysis
1821
2 conditions with high frequency of uro-epithelial cancer
Analgesic Abuse Nephropathy, Aristocholic Acid Nephropathy
1822
Acute Interstitial Nephritis is a ___ reaction
immune-mediate hypersensitivity
1823
Papillary necrosis is mostly associated with
infection
1824
Granular casts mean that there is what in sediment
Renal tubular cells
1825
Eosinophils in pyuria indicated what
Allergic reaction
1826
Study of choice for kidney stone evaluation
CT w/out contrast
1827
Acute Phosphate Nephropathy presents with
Renal insufficiency several weeks after exposure
1828
Tx of Contrast-Induced Nephropathy
Usually reversible and can be managed with supportive care, not dialysis
1829
2 most common causes of Papillary Necrosis
DM w/ infection, Obstruction w/ infection
1830
3 Tubular Dysfunction from Analgesic Abuse Nephropathy is characterized by
Hyperkalemic, Hyperchloremic RTA (Medulla and CD injury); Nephrogenic DI (Medulla injury)
1831
PCKD is associated with what CNS finding
Intra-cranial Aneurysms
1832
Acute Uric Acid Nephropathy is due to
AKI caused by patients with cancer
1833
Tx of ATN
Dialysis, but after tx of shock and organ failure
1834
ATN with Vacuolization and Calcium Oxalate
Ethylene Glycol
1835
Common source of hematogenous infection leading to pyelonephritis
Central Venous Catheter - Staph Aureus
1836
Presence of a few renal cortical cysts is clinically significant
No, common finding in older adults with no clinical signficance
1837
Mutations in AD (Adult) PCKD
Polycystin-1 or -2
1838
Prognosis for AR PCKD
Immediate untreatable respiratory failure at birth
1839
Potassium over __ is a medical emergency
7 mMol/L
1840
T/F: Biopsy is often needed to dx etiology of AKI
False, unlike Nephrotic and Nephritic syndromes
1841
Symptoms of ATN
Anorexia progressing thru nausea to vomitting, along with pruritis and confusion
1842
When do patients with AD PCKD start getting symptoms? Is the progression of this disease rapid?
30s, no gradual
1843
Mutation in Fibrocystin
AR (Childhood) PCKD
1844
Analgesic Nephropathy causes
Chronic Interstitial Nephritis and Papillary Necrosis
1845
autosomal recessive diseases of cilia components leading to end-stage renal disease in children
Nephronopthisis-Medullary Cystic Disease Complex
1846
Which is reversible: ATN or Glomerular Necrosis
ATN
1847
4 gross complications of Acute Pyelonephritis
Pyenephrosis, Perinephric Abcess, Acute Papillary Necrosis, Scars
1848
Ascending pyelonephritis in patients >1 is associated with
Vesicoureteral Reflux
1849
Most common genetic cause of end stage renal disease in children
Nephronopthisis-Medullary Cystic Disease Complex
1850
As injury crosses line of irreversibility in ANT, the cells
undero coagulative necrosis and slough into the lumen (contributing to casts)
1851
Gross changes in ATN
Kidneys enlarged up to 30%, with pale cortex and congested medulla
1852
most common histopathologic counterpart to moderate-severe acute kidney injury
ATN
1853
Acute Pyelonephritis produces what type of necrosis
Liquefactive --> Abcessing
1854
Primary leukocyte in Acute Pyelonephritis
Neutrophils
1855
Patients with Acute Pyelonephritis may have flank pain, with corresponding physical sign of
Costovertebral Angle Tenderness
1856
Perinephric Abcess
Necrotizing pyelonephritis infection spreads thru renal capsule into surrounding fat
1857
One of the earliers LM findings of ATN
Loss of brush border and bleb formation
1858
Symptoms of ATN are the sames as symptoms of
AKI
1859
Most common cause of ischemia leading to ATN
Shock, especially septic
1860
Prognosis for AD PCKD
Avg patient needs dialysis or transplant at 50
1861
Common symptoms of AD PCKD
Flank pain or dragging sensation in the abdomen
1862
Abrupt impairment in renal fxn manifested by increased creatinine, BUN, and Oliguria
AKI
1863
Histology of ATN
Blebbing, Vacuolization, Loss of BB, Flattening, Necrosis and Sloughing
1864
Why is the percent of AKI represented by ATN not known
Rarely biopsied
1865
More diffuse gross pyelonephritis rather than foci indicates what route of infection
Vesicoureteral Reflux
1866
Depressed cortical scars indicates what about Pyelonephritis
Hematogenously spread chronic
1867
Why does AR (childhood) PCKD lead to immediate untreatable respiratory failure at birth
Pulmonary Hypoplasia
1868
Diffuse vacuolated tubular cells with no glomeruli or tubules in field
Renal Cell Carcinoma
1869
Muddy Brown Granular Casts or Tubular Epithelial Casts are a diagnostic feature of ___ in up to ___ percent of cases
ATN, 80%
1870
Most common cause of acute kidney injury
Ischemia --> ATN
1871
Renal ischemia usually spares the
Glomeruli
1872
Thyroidization
Chronic Pyelonephritis
1873
Cysts in medulla, which generally do not impair renal fxn or effect prognosis of patient as whole
Medullary Sponge Kidney is characterized by
1874
Genes mutated in Nephronopthisis-Medullary Cystic Disease Complex are __ components
Ciliary
1875
Most specific cell type for Interstitial Nephritis
Eosinophils
1876
Enlarged kidney, Pale cortex, Congested Medulla
ATN
1877
Interstitial nephritis is either rich in ___ or ___
Eosinophils and Neutrophils (Type 1), or Macrophages with Giant Cells and Granulomas (Type 4)
1878
Foci of pyelonephritis grossly means what route of infection
Hematogenous
1879
Pyelonephritis essentially means
bacterial infection of kidney
1880
Most common histopathologic counterpart of AKI
Acute Tubular Necrosis
1881
Mutation in AR PCKD
Fibrocystin
1882
Ascending Pyelonephritis in babies is associated with
Congenital malformation of valves b/t ureters and bladder
1883
Most common cause of Intersitial Nephritis
Immune-mediated reaction to medication
1884
Cortical hemorrhages
ATN
1885
Necrosis --> Liquefaction --> Abcesses
Acute Pyelonephritis
1886
Mutations in Polycystin-1 or -2
AD (Adult) PCKD
1887
Acute Pyelonephritis characteristically produces
Intense neutrophilic infiltration w/ liquefactive necrosis leading to abcess formation
1888
Second most common cause of ATN after ischemia
Nephrotoxins
1889
Small kidneys w/ numerous small cysts at corticomedullary junction and chronic tubulointerstitial nephritis and fibrosis
NMCDC
1890
What causes Myoglobin casts
Necrosis of skeletal muscle (Rhabdomyolysis)
1891
Most common cause of Acute Pyelonephritis
E Coli
1892
Why are GI hemorrhage and epistaxis common in ATN
Platelets not functioning properly
1893
What presentation suggests drug-induced acute interstitial nephritis
New-onset azotemia w/ oliguria, fever, skin rash, and especially eosinophilia
1894
Most common cause of ATN
Ischemia (75%)
1895
New-onset azotemia w/ oliguria, fever, skin rash, and especially eosinophilia suggests
Drug-induced acute interstitial nephritis
1896
Key determinant of which ATN patients need dialysis
Potassium (hyperkalemia)
1897
Baseline normal renal tubule histology
Cuboidal cells with granular eosinophilic cytoplasm
1898
Pyenephrosis
Infected pus fills and distends the renal calyces, pelvis, and ureter
1899
Presence of Small-moderate numbers of globally sclerotic glomeruli is clinicaly significant?
No, common finding in older adults with no clinical signficance
1900
What causes Thyroidization? What condition has this?
Fibrosis and tubules distended with inspissated urine, making them look like thyroid follicles; Chronic Pyelonephritis
1901
What percent of AIN is due to drug reactions
75%
1902
BP in ATN
Usually low, because usually caused by septic shock
1903
Hematogenous pyelonephritis is most commonly due to
Staph Aureus
1904
Two regions of renal tubule most vulnerable to acute ischemic necrosis
PST, Ascending Thick Limb
1905
Timeline of Intersitial Nephritis after expsoure to offending drug
15 days
1906
Good evidence that you're in recovery phase after AKI
Mitotic figures
1907
Urinalysis feature of ATN
Muddy Brown Casts
1908
Prognosis for Acute Pyelonephritis
Good
1909
With chronic pyelonephritis, there is usually ___, primarily with __ and ___, primarily involving ___
Usually inflammation, primarily involving lymphocytes and plasma cells, primarily involving the interstitium
1910
Kidney injury caused by Rhabdomyolysis
Myoglobin precipitates in renal tubules causing ATN
1911
Recurring or chronic Pyelonephritis is associated with
Scarring
1912
Region of kidney most susceptible to ischemia
Outer medulla
1913
Gross pathology of Acute Pyelonephritis
Dark red congestion; Areas of tan suppurative inflammation (some with necrosis, some becoming abcesses)
1914
What type of necrosis is seen in ATN
Coagulative
1915
Area of dark blue in microscopic path of Renal Abcesses
Nuclear debris from breakdown of dead cells (especially neutrophils)
1916
Male-Female preponderance of Pyelonephritis
Males under one, females b/t 1 and 50
1917
Electrolytes and Acid Base in ATN
Hyperkalemia and Metabolic Acidosis; Sometimes Hyponatremia
1918
Is ATN reversible?
Yes, because tubules can regenerate their epithelial cells
1919
Two options for quick tx of Hyperkalemia
IV Calcium Gluconate, IV Insulin + Glucose
1920
Medullary Sponge Kidney is characterized by
Cysts in medulla, which generally do not impair renal fxn or effect prognosis of patient as whole
1921
T/F: Most drug reactions cause interstitial nephritis
False, but most intersitial nephritis is caused by drug reactions
1922
Myoglobin Casts indicate
Rhabdomyolysis cause ATN - myoglobin precipitated in renal tubules
1923
Classic triad of Intersitial Nephritis
Fever, rash, eosinophilia
1924
Most common nephrotoxic cause of ATN
Radiologic contrast dye
1925
___ is a disease of chronic intersitial nephritis and papillary necrosis
Analgesic Nephropathy
1926
Ethylene Glycol poisoing causes ATN with what 2 features
Prominent cytoplasmic vacuolization and oxalate crystals
1927
Why does ATN cause cortical hemorrhages? Why are they triangular?
Disease of intrarenal arteries that causes ischemia and then allows reperfusion
1928
Infiltrating cells in Acute vs Chronic Pyelonephritis
Neutrophils vs Lymphocytes and Plasma Cells
1929
Fibrosis + Distended tubules w/ inspissated urine, making them look like thyroid follices
Chronic Pyelonephritis
1930
Globally sclerotic glomeruli, dilated tubules resembling thyroid follicles, interstial fibrosis
Microscopic appearance of end stage kidney in DN
1931
Stage 4 of DN
GFR < 75mL/min - HTN ubiquitous
1932
Condition that will cause Hyaline Sclerosis in both efferent and afferent arterioles
DM
1933
% of diabetics who develop nephropathy
30-40%
1934
Features of Nodular Type Diabetic Glomerulopathy
Kimmelstiel Wilson nodules and Hyaline sclerosis of both arterioles
1935
Patients taking ACEi's or ARB's should be monitored for
Hyperkalemia
1936
End Stage kidney from Diabetic Nephropathy looks just like
HTN Nephropathy
1937
Nodular Glomerulosclerosis (Kimmelstiel Wilson Disease) correlates with
Renal failure eventually requiring dialysis
1938
How do you distinguish diabetic nephropathy from most other forms of CKD
Glomeruli and kidneys are typically normal or larger in DN; in others, renal size is usually reduced
1939
Diffuse type Diabetic Glomerulopathy consists of
Capillary BM thickening; Increased MM
1940
How does Glucose lead to Glomerular Pressure increase
Glucose provides osmotic diuretic effect --> Incr renal filtration --> Glomerular hypertophy --> Glomerular pressure incr
1941
Macroalbuminuria is aka
Overt Nephropathy
1942
Macroalbuminuria is defined as
random urine albumin/creatinine over 300 mg/g
1943
Micro-Albuminuria is defined as
> 30 mg/g loss
1944
Most common type of Diabetic Glomerulopathy
Diffuse
1945
Reduction in proteinuria is associated with
Reduced risk for ESRD
1946
Where do fibrosis and scarring occur in Glomerular HTN
Both glomerular and tubular elements of nephron
1947
Kimmelstiel Wilson nodules and Hyaline sclerosis of both arterioles
Features of Nodular Type Diabetic Glomerulopathy
1948
What causes fibrosis and scarring in Glomerular HTN
Tubular inflammation and renal microvascular injury from protein leakage
1949
Which drug has been shown to slow rate of diabetic nephropathy more than others
ACEi
1950
What causes injury to tubular cells in Glomerular HTN
G HTN --> Injury to GBM --> Leaks plasma proteins --> Attempts to reabsorb these proteins injures tubular cells
1951
Fibrin caps
Crescentic deposits of condensed leaked plasma proteins
1952
Avg time to progression from stage 1 to stage 4 in DM1
17 years
1953
Microscopic appearance of end stage kidney in DN
Globally sclerotic glomeruli, dilated tubules resembling thyroid follicles, interstial fibrosis
1954
At what stage of DN is the condition essentially irreversible?
Stage 4
1955
Stage 5 of DN
GFR less than 10 (ESRD)
1956
___ is marker for increased CV risk in DN
Microalbuminuria
1957
Higher baseline Albuminuria =
Faster rate of progression
1958
Fasting blood glucose criteria for DM
126 mg/dL
1959
Anti-hypertensives to use in diabetics
ACEi's and ARB's
1960
TGF-beta has been implicated in many ___ diseases
Chronic, Scarring
1961
T/F: Patients with macroalbuminuria are more likely to die than develop ESRD
TRUE
1962
What condition has Kimmelstiel Wilson nodules
Nodular Type Diabetic Glomerulopathy
1963
Hyaline Sclerosis of Afferent and Efferent Arterioles in DM vs HTN
HTN causes hyaline sclerosis of afferent, whereas DM will affect both
1964
Diffuse type Diabetic Glomerulopathy is identical to that which occurs in
HTN and aging
1965
Microalbuminuria in DN over time leads to
Overt Proteinuria, Reduced GFR, HTN
1966
What starts the clinical phase of DN
Overt Proteinuria
1967
Tubular inflammation and injury from Glomerular HTN activates pathways that lead to
Fibrosis and Scarring
1968
Where in glomerulus do Kimmelstiel Wilson nodules occur
Periphery of Glomerular Tuft
1969
For almost all kidney disease, including DN, likelihood of dying from what is higher than reaching ESRD
CV disease
1970
Top 2 causes of ESRD
Diabetes (43%), HTN (23%)
1971
Where in glomerulus do Fibrin Caps occur?
Overlying peripheral capillaries
1972
Classic symptoms of hyperglycemia
Thirst, Polyuria, Poldipsia, Visual Blurring
1973
Which type of Diabetic Glomerulopathy is characteristic (specific) for DM
Nodular Type
1974
What occurs earlier than microalbuminuria in DN
Changes to GBM structure (collagen IV deposition)
1975
Why does RAAS play a role in diabetic nephropathy
Inefficient at shutting down RAAS production
1976
At what stage of DN do patients require dialysis or transplantation
Stage 5
1977
How is Albuminuria calculated
Albumin / Creatinine to correct for diffs in urine concentration
1978
At what stage of DN does kidney demonstrate an inability to adequately filter wastes
Stage 3 - Creatinine and BUN rise
1979
Stage 1 of DN
Hyperfiltration - Kidney incr in size
1980
How does glucose lead to Premature Glomerulosclerosis
Osmotic Diuretic Effect --> Incr filtration --> G pressure incr --> Hypertrophy --> G cell failure --> Premature Glomerulosclerosis
1981
___ lower both arterial BP and glomerular capillary pressures
ACEi's and ARBs
1982
By the time of Macroalbuminuria (over nephropathy), over 90% of patients have
HTN
1983
What causes inflammation in tubular cells in Glomerular HTN
G HTN --> Injury to GBM --> Leaks plasma proteins --> Attempts to reabsorb these proteins injures tubular cells --> Inflammation
1984
Nodular Type Diabetic Glomerulopathy occurs after how many years
10
1985
Kimmelstiel Wilson nodules eventually
squeeze capillaries shut
1986
Where in glomerulus do Capsular drops occur
Parietal layer of Bowman's Capsule protruding into urinoferous space
1987
Development of ___ heralds rapdid decline in GFR in Type2 DM
Macroalbuminuria
1988
Once in ____, patient is unlikely to regress
Overt Proteinuria (macroalbuminuria)
1989
2 types of Exudative lesions
Fibrin Caps, Capsular Drops
1990
Stage 3 of DN
Macro-Albuminuria, Creatinine and BUN levels rise, BP rises
1991
Most common cause of kidney failure
DM
1992
ACEi's have been show to lower BP and also reduce ___
Microalbuminuria (lower glomerular capillary pressure)
1993
Which is specific for diabetic glomerulopathy: Capsular Drops, Fibrin Caps
Capsular Drops
1994
Avg time to progression from stage 1 to stage 5 in DM1
23 years
1995
Capsular Drops
Deposits of partly plasma proteins, and partly basment membrane
1996
On which arteriole does Ang2 selectively act?
Efferent --> Incr intraglomerular pressure
1997
Deposits of partly plasma proteins, and partly basment membrane
Capsular Drops
1998
Diabetics Microvascular Complications are eliminated if patient obtains optimal management of glucose, BP, and lipid levels
FALSE
1999
Effects of Glomerular HTN
Injury of GMB --> Leak proteins --> Injury to tubular cells and inflammation
2000
First clinically detectable abnormality of DN
Microalbuminuria
2001
Outcome of increased glomerular pressure and subsequent hypertrophy
Premature Glomerulosclerosis
2002
Stage 2 of DN
Clinically evident: Micro-albuminuria, BP rises, glomeruli show damage
2003
How does TGF-beta get activated? What is consequence?
Ang2 --> TGF-beta --> Proliferation of fibroblasts and tubuloepithelial cells --> Hypertrophy, BM thickening, MM expansion
2004
Gross appearance of End stage kidney in Diabetic Neprhopathy
Diffuse fine granularity of cortical surface = Nephrosclerosis
2005
Crescentic deposits of condensed leaked plasma proteins
Fibrin caps
2006
3 histological features of DN
Incr MM, Glomerular Collapse, Glomerulosclerosis
2007
___ reduction determines CV outcome
Proteinuria
2008
Effect of Ang2 in DN
Selective constriction of efferent>afferent --> Incr SNGFR --> Incr intraglomerular pressure --> Glomerular HTN
2009
When to suspect Light Chain Disease
Nephrotic Syndrome or Rapidly progressive tubulointersitial nephritis, associated with cardiac diastolic dysfunction and monoclonal Ig in urine or serum
2010
What percent of patients with HgB SS will develop ESRD
4-12%
2011
Glomular histology is sickle cell patients who present with chronic renal disease and proteinuria
Glomerulomegaly, Mesangial expanion, Segmental sclerosisi
2012
AA amyloidosis is due to
Chronic inflammatory diseases such as RA, IBD, etc.
2013
Later Stages of Sickle cell nephropathy
Interstitial inflammation, edema, fibrosis, tubular atrophy, papillary infarcts
2014
In the kidney, mixed cryoglobulinemia most often causes what pattern of injury
Membranoproliferative
2015
Tubular and insterstitial deposits of amyloid may lead to
Tubular Atrophy and Interstitial fibrosis
2016
Light chain disease presents with
Proteinuria and Renal Failure
2017
Significant proteinuria but only minimal peripheral edema
HIV Nephropathy
2018
Concentrating ability in Sickle Nephropathy
Diminished
2019
Where in kidney does sickling usually occur
Vasa Recta
2020
HIV Nephropathy Histology
Collapsing FSGS, with Microcystic Tubular Dilation, Intersitial inflammaiton and fibrosis
2021
Susceptibility gene for HIV Nephropathy
APOL1
2022
GFR in sickle cell
Increased until 4th decade, then decreased
2023
Big kidneys on US
Diabetic Nephropathy, Amyloidosis
2024
Ig capable of binding IgG
RF
2025
What distinguishes HIV-associated nephropathy from idiopathic collapsing FSGS
Accompanying prominent tubular dilation and interstitial inflammation
2026
Proteins in Cryoglobulinemia
Ig's, Complement, RF
2027
Most patients with AL just have
Monoclonal Gammopathy, instead of Multiple Myeloma
2028
Question to ask with Collapsing FSGS
HIV Test?
2029
Cryoglobulins can be polyclonal Ig's produced by
Chronic Inflammation
2030
Presence of proteins in serum, which precipitate w/ cooling serum below normal body temp
Cryoglobulinemia
2031
AL amyloidosis can present with
Nephrotic syndrome, Restrictive CM, Diarrhea, and nonspecific
2032
Early stages of sickle cell nephropathy
Glomerular Hypertrophy, hemosiderin deposits, focal areas of hemorrhage and necrosis
2033
IF of Light Chain Disease
Positive in glomerular capillary loop, mesangium, and tubules
2034
Coinfection of HIV and Hep C
Mixed Cryoglobulinemia
2035
Characteristic LM appearance of Light Chain Disease in Glomerulus
Nodular glomerulosclerosis, w/ expansion of MM
2036
Sickle cell disease can cause __, although diabetes is much better known for it
Renal Papillary Infarcts
2037
Pattern of injury in Cryoglobulinemia
Membranoproliferative
2038
Cryoglobulinemia
Presence of proteins in serum, which precipitate w/ cooling serum below normal body temp
2039
Amyloidosis seen in long-term hemodialysis
Beta-2 Microglobulin
2040
AA amyloid is derived from
SAA protein
2041
Mixed Cryoglobulinemia is associated with ___ in a very high % of cases
Hep C
2042
Mixed Cryoglobulinemia most often produces what types of symptoms
Constitutional and Nonspecific
2043
End Stage of Sickle Cell Nephropathy
Glomerular Enlargement and FSGS
2044
Cryoglobulinemia can be asymptomatic or result in
Immune-complex-mediated GN or Vasculitis
2045
Median survival of AL amyloidosis
10 months
2046
Limits deposition of AA fibrils
Eprodisate
2047
Tx of AL Amyloidosis
Melphalan and Dexamethasone
2048
Protein in AL amyloidosis
Ig light chain
2049
Ages for Amyloidosis
Late middle age and older
2050
Triopathy
Retinopathy, Neuropathy, Retinopathy in Diabetes
2051
Kidney symptoms in AL amyloidosis
Nephrotic syndrome, Renal insufficiency w/ enlarged kidneys
2052
Gross appearance of advanced amyloidosis
Enlarged, pale organs with waxy texture
2053
How to distinguish Diabetic Retinopathy from Light Chain Disease
IF shows only lambda or kappa positivity in light chain disease
2054
What is necessary for amyloidosis
Extracellular Fibriloogenic Environment: GAG, serum amyloid P, laminin, Collagen IV, apo E
2055
Light Chain Disease glomerular LM strongly resembles
Diabetic Nephropathy
2056
Advanced renal amyloidosis results in what kind of glomerulopathy
non-proliferative, non-inflammatory
2057
Beta 2 Amyloid occurs with
long-term hemodilaysis
2058
Beta 2 microglobulin is a component of
MHC class 1 molecules
2059
B cell lymphoproliferative disorder characterized by deposition of immune complexes containing RF, IgG, HCV RNA, and complement on endothelial surfaces, eliciting vascular inflammation
Mixed Cryoglobulinemia
2060
Interstitial fibrosis and Vascular Sclerosis with abundant brown pigment (Hb breakdown products)
Sickle Cell Nephropathy
2061
Most common renal manifestation of AA amyloidosis
Nephrotic syndrome
2062
Presentation of HIV Nephropathy
Progressive Azotemia, Significant Proteinuria, Minimal peripheral edema
2063
How does Sickle Cell Nephropathy most commonly manifest?
Proteinuria
2064
Hereditary Amyloidosis
Replacement of single AA --> Renders protein prone to fibril formation
2065
Pseudothrombi in capillary lumens in glomerulus
Cryoglobulinemia
2066
Eprodisate
Limits deposition of AA fibrils
2067
Monoclonal cryoglobulins typically produce signs and symptoms related to
Hyperviscosity and/or thrombosis
2068
Pathology of HIV Nephropathy
Collapsing Form of FSGS
2069
Median age at dx of AL amyloidosis
64
2070
Most commonly dx type of amyloidosis
AL
2071
Main target organ of AA amyloidosis
Kidney
2072
__ proteins can precipitate in tubules where epithelial cells coalesce into a syncytium around them
Bence Jones
2073
Glomerulomegaly, Mesangial Expansion, Tubular epithelial hemosiderin accumulation, Interstitial fibrosis and vascular sclerosis
Sickle Cell Nephropathy
2074
___ is a unique feature of the collapsing FSGS associated with HIV
Microcystic Tubular Dilatation
2075
Most amyloiogenic proteins are made in
Hepatocytes or plasma cells
2076
Light chain disease vs AL amyloid
deposits are congo red negative and have no fibrillar organization
2077
Tx of AA amyloidosis
Eprodisate
2078
Beta 2 amyloid tends to deposit
Synovium, joints, and tendon sheaths
2079
Membranoproliferative pattern of injury with deposition of immune complexes containing RF, IgG, Hep C virus RNA and complement factors on endothelial surfaces and in subendothelial and mesangial locations
Mixed Cryoglobulinemia
2080
HIV-associated nephropathy results from
Direct infection of renal epithelial cells in genetically susceptible host
2081
Podocyte proliferation
HIV Nephropathy
2082
Cryoglobulins can be monoclonal Ig's produced by
Multiple Myeloma
2083
How can you tell if kidney is involved
WBC Casts
2084
Blood culture when pyelonephritis
Will be positive
2085
Fever, Chills, Flank pain, CVAT =
Upper Tract Infection
2086
Abx most effective in both Complicated and Uncomplicated UTI
Cipro
2087
Why is there an increased rate of UTI in pregnancy
Progesterone lowers motility --> Stagnate urine
2088
pH of 8 =
Urea-splitting bacteria (Struvite)
2089
How does contraception affect rate of UTI
foreign body contraceptives increase rate
2090
2 Abx for Pyelonephritis that have lowest renal concentrations
Cephalothin, Ampicillin
2091
Abx most effective in complicated but not uncomplicated
Ceftriaxone, Gentamicin
2092
What percent of UTI bactereria come from GI
95%
2093
Catheter in bladder =
colonization w/ water-loving bacteria that start with P
2094
UTI + Obstruction =
Papillary Necrosis
2095
2 main causes of Dysuria
Classic Cystitus (50%), Acute Urethral Syndrome (40%)
2096
Male vs female in elderly
Male catch up due to impaired flow (BPH)
2097
Painless hematuria =
Cancer
2098
Two most common organisms in UTI
E coli, Staph saprophyticus
2099
Receptor for bacterial fimbriae on uroepithelium
P blood group antigen
2100
WBC casts indicate
kidney involvement
2101
Antibiotic duration in men vs women
Longer use in men because there must be something structural
2102
Frequent cause of altered mental status
Infection
2103
Recurrent gonorrhea causes
Urethral stricture
2104
Male vs female in infants
Male > Female
2105
Virulence factor that impairs phagocytosis
K antigen (capsular polysaccharides)
2106
How does preganancy affect rate of pyelonephritis
Greatly increases
2107
Acute Urethral Syndrome vs Classic Cystitus
Classic is > 10^5 cfu/mL, Acute Urethral is
2108
2 frequent causes of hematogenous UTI
Bacterial endocarditis, Indwelling venous catheters
2109
Why do UTI's more frequently progress in pregnant women?
Immunosuppressive state
2110
Struvite Renal Calculi occur in patients with
some abnormality of tract
2111
Organism in young females that aren't too sick
Staph Saprophyticus
2112
T/F: Hematuria is a common feature of UTI
false, should be thinking more tubulointersitial disease
2113
Significant bacteruria is what amount
>15^5 cfu
2114
In Acute Urethral Syndrome, inflammatory response is limited to
the Urethra
2115
If multiple organisms in urine culture
Reported as contaminated (False positive)
2116
Role of Tamm-Horsfall in UTI
Thought that it may inhibit colononization and adherence
2117
2 signs of contaminated urine culture
Multiple organisms, Lots of squamous cells
2118
Though inward conductance is greater than outward, K efflux does not occur b/c
Vm is more positive than EK
2119
What provides driving force for K excretion in DT epithelial cells
Na absorption --> Depolarizes membrane
2120
Tx for hyperkalemia is required if
EKG changes
2121
What mediates reabsorption of peptide-like drugs
Peptide Transporters (PEPT1, PEPT2)
2122
NSAID use in CKD will cause
Acute reductions in renal bloodflow and GFR
2123
PGI2/PGE2 preserve GFR by antagonizing arteriolar vasoconstrictors and
blunting mesangial and podocyte contraction
2124
Drugs that antagonize ___ increase risk of AKI when NSAID is administered
Drugs that antagonize RAAS
2125
Effect of PG's on ADH
Inhibit cAMP synthesis and oppose ADH --> Water excretion
2126
Effect of PG's on RAAS
Stimulate Renin secretion --> Enhance Na retention and K secretion
2127
What provides driving force for reabsorptio of drugs and drug metabolites
Extensive reabsorption of filtered water
2128
Why doesn't K efflux thru ROMK at physiological intracellular Mg
Intracellular Mg binds ROMK and blocks K efflux
2129
Low magnesium can exacerbate ___ by ___
K wasting by incr K secretion in DT
2130
Most common cause of drug-induced hypokalemia
Anti-infective agents
2131
Acute NSAID toxicity is manifest in terms of
Tubular Epithelial Necrosis secondary to altered renal hemodynamics
2132
Anti-infective agents commonly cause what electrolyte abnormality
HypoKalemia
2133
Diureti-induced hypokalemia is associated with
Mild-Moderated Metabolic Alkalosis
2134
Effects of PG's on LOH and Distal Nephron
(1) Incr renal Na excretion, decr medullary tonicity; (2) Stimulate Renin secretion; (3) Inhibit cAMP and oppose ADH
2135
Effect of PGE2 on cellular transport of NaCl
Decreases cellular transport of NaCl --> Increase Na excretion and decr in medullary tonicity
2136
2 commonly used formulas that estimate GFR
Cockroft-Gault; MDRD
2137
Kidney PGs have their major role in
preservation of renal fxn when pathologic states supervene and compromise physiologic kidney processes
2138
3 steps in hyperkalemia tx
(1) Calcium Gluconate, (2) Shift to intracellular, (3) Removal of excess K+
2139
Effect of PGI2 and PGE2 in kidney
Vasodilation of interlobular arteries, afferent and efferent arterioles, and glomeruli
2140
Risk of NSAID-associated AKI in health persons
Low, b/c PG production is low in healthy persons
2141
Second most common cause of drug-induced hypokalemia
Diuretics
2142
What can be used to remove K+ in patients with renal failure
Dialysis
2143
Net effect of PG actions on LOH and Distal Nephron is that chronic NSAID consumption can lead to
a mild, dose-dependent increase in BP
2144
T/F: PGs are a primary regulator of renal function
False, minimal importance in kidney of health individuals with normal volume status
2145
GFR > ___ is normal
80
2146
At physiological intracellular Mg concentration, ROMK conducts K in which direction
Inward
2147
COX-2 inhibitor effects on kidneys
equivalent to other classes with respect to their nephrogenic potential
2148
NSAIDs are also associated with interstitial nephritis that is thought to be result of
Allergic reaction
2149
GFR < ___ is severe renal impairment
30
2150
Perfusion rate limited
extraction ratio is not limited to the unbound fraction of drug
2151
3 conditions with increased prevalence that are exacerbated by GFR
HTN, CHF, Renal insufficiency
2152
How does insulin lower hyperkalemia
Stimulates Na/H exchange --> Na in --> Stimulates Na/K --> Uptake of K into cell
2153
PG production is increased in ___ disease
chronic kidney disease
2154
Leading causes of drug-induced hyperkalemia
Aldosterone antagonist/k-sparing agents and ACEi/ARB
2155
Organic anion and cation transporter systems, w/ overlapping specificities, allow potential for
Drug-Drug interactions
2156
___ locally mediate effects of both systemic and locally produced vasoconstrictor hormones
Eicosanoids
2157
K secretion in DT is under regulation of
intracellular Mg
2158
Tubular secretion occurs primarily in
pT
2159
3 effects of Calcium in HyperKalemia
(1) Less neg resting Vm; (2) Shift upwards and right of Vm x Vmax curve; (3) Reverses depressed conduction
2160
Capacity rate limited
Extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in RBCs
2161
Action of Albuterol tx of Hyperkalemia
Activates Na/K --> Na leaving forces K in
2162
2 peptide-like drugs
beta-lactams, ACEi's
2163
2 "situations" when PG's play role in preserving renal fxn
True intravascular volume depletion; Effective decrease in renal blood flow
2164
Surge in catecholamines is often associated with what electrolyte change
Hypokalemia
2165
With no Mg and normal K concentrations, the chemical gradient drives K in which direction?
Outward
2166
2 drugs commonly used to tx Hyperkalemia
B2 agonist (Albuterol) and Insulin
2167
Insulin stimulates what transporter
Na/H exchange (Na in, H out)
2168
PGI2/PGE2 antagonize
local effects (vasoconstriction) of circulating Ang2, Endothelin, Vasopressin, and Catecholamines (that would normally maintain systemic pressure at expense of renal circulation)
2169
What aspect of tubular secretion allows for drug-drug interactions
Transporters with overlapping substrae specificities
2170
Coca Cola urine =
Rhabdomyolysis
2171
Toxicity of Cyclophosphamide
Meylo; Hemorrhagic Cystitis (mesna)
2172
Maculopapular rash, mucositis, anemia, fatigue
Rapamycins
2173
IFN-alpha 2b is used off label to treat
Clear Cell RCC
2174
Pharmacologic support for patients taking Aldesleukin
Abx, Dopamine for GFR, Phenylephrine for BP support, Fever and Chills, PPI for hyperacidity
2175
Destructive metastic RCC sites
Lung Liver Bone
2176
Black box warnings for Bevacizumab
Hemm, GI perforations, Wound healing complications
2177
Action of Insulin on K levels
Na/H exchanger --> Drives K from blood into cells --> Serum K drops
2178
Patients taking Aldesleukin have high potential for
Sepsis
2179
Spironolactone causes what in men
Gynecomastia (similar structure to steroids)
2180
Dactinomycin Toxicity
Myelo; Hepatic Dysfuncion, Infection
2181
Toxicity of Carboplatin
Myelo; Infection
2182
Cockroft-Gault Formula
accounts for age and sex
2183
mTOR blockers
Everolimus, Temsirolimus
2184
Mesna
Antidote to Cyclophosphamide and Ifosfamide
2185
Black box warnings for IFN-alpha 2b
Neuropsych, AI, Ischemic and Infectious disorders
2186
3 causes of Hyperkalemia mention by sweatman
Lysis, Statins, Crush injury
2187
Most common adverse effects of IFN-alpha 2b
Fatigue, fever, flu-like symptoms; Leukopenia, Neutropenia
2188
Standard chemo agents for Wilm's post nephrectomy
Vincristine, Dactinomycin, Doxorubicin (Cyclo, Etoposide)
2189
Etoposide Toxicity
Hematologic Toxicity; BP instability
2190
Sign of Rhabdomyolysis
Coca Cola urine
2191
Effect of Insulin on heart
Cardiotonic, independent of Beta1
2192
__ are contraindicated in Bilateral RAS
ACEi's and ARB's
2193
Tx of BB or CCB overdose
Insulin + Glucose
2194
Drug that causes Hypotension
Bevacizumab
2195
Bilateral sensory "stocking-glove"
Vincristine
2196
In fit patients with mets at dx and minimal symptoms, what provides the best survival strategy
Nephrectomy followed by IFN-alpha
2197
Patients with Bilateral RAS are dependent on ___ to maintain renal perfusion
RAAS
2198
How does HypoMg cause HypoK
Doesn't allow K to exit ROMK channel, just enter
2199
Only approved as follow up therapy after failure of initial drug
Axitinib
2200
Most common metastatic site for RCC
Lymph Nodes
2201
Route of Temsirolimus vs Everolimus
Weekly IV vs Daily Oral
2202
Ifosfamide Toxicity
Hemorrhagic Cystitis (mesna)
2203
At physiological Mg concentrations,
Mg occludes ROMK channel, preventing K from exiting cell
2204
2 CYP substrates
TKIs, Rapamycins
2205
Patients taking this drug have high potential for sepsis
Aldesleukin
2206
Renal fxn in men vs women
Higher in men
2207
Most drugs for adult RCC target
VEGF due to etiology from vHL mutations
2208
Axitinib
Only approved as follow tx after failur of initial drugs
2209
Cytotoxic chemo in Adult vs Pediatric RCC
Ineffective in adults
2210
Chronic NSAID tx is not good for
elderly patients, especially if taking anti-HTN
2211
Adminstration of high dose IL-2 is akin to
Induction of controlled state of septic shock
2212
Results of clinical trials with low dose intermittent pulse IL-2
Disappointing
2213
Hepatic Dysfunction Tox
Dactinomycin
2214
Admin of Aldesleukin
IV to hospitalized patients
2215
Endogenous IFN activation results in transcriptional upregulation of
Genes responsible for Anti-viral, Anti-proliferative, and Anti-tumor activities
2216
Admin of IFN-alpha 2b
SC 3 x weekly
2217
Low dose infusion of IL-2 leads to selective expansion of
A subset of NK cells that overexpress high affinity IL-2 receptor
2218
Patients with recurrent Clear Cell Sarcoma involving brain respond to
ICE: Ifosfamide, Carboplatin, Etoposide
2219
Resistance to the Rapamycins (-limus)
Second mTOR complex
2220
Sorafenib blocks
VEGFR, PDGFR, KIT, RAF
2221
Pulmonary Infiltrates
Temsirolimus and Everolimus
2222
Fatigue, Fever, Flu-Like symptoms
IFN-alpha 2b
2223
Aldesleukin (IL-2) and IFN-alpha are used in treatment of
Clear Cell RCC
2224
WAGR and Denys-Drash are both associated with abnormalities of
Wilms Tumor 1 gene
2225
2 different appearances of Papillary Carcinoma depending on angle of section
Nipples vs Papillae
2226
Does RCC spread better hematogenously or by lymph
About equal
2227
Most common type of renal cell carcinoma
Clear cell
2228
Which subtype is more prone to bilateral or multifocal tumors
Papillary
2229
loss of genetic imprinting that normally silences allele controlling ILGF2
Beckwith-Wiedemann Syndrome is associated with
2230
3 congenital malformations associated with Wilms Tumor
WAGR Syndrome, Denys-Drash, Beckwith-Wiedemann
2231
Large pale cells with prominent cell membranes
Chromophobe Carcinoma
2232
Risk factors and average age for renal cell carcinoma
Smoking, HTN, Obesity - 64 years
2233
Origin of Renal Cell Carcinoma
Renal Tubular Epithelium
2234
Behavior of Oncocytoma
Benign
2235
Chromophobe Renal Cell Carcinomas
Large pale cells with prominent membranes
2236
Chromophobe RCC is positive for
Hale's colloidal iron stain
2237
Genetic signature of Oncocytoma
None
2238
Abundant cytoplasmic little red bacteria-size dots
Mitochondria in Oncocytoma
2239
Genetics of Papillary RCC
MET mutation
2240
What is predictably common in renal cell carcinomas
Hemorrhage - tumoral blood vessels are abnormal and prone to rupture
2241
Where do Renal Cell Carcinomas spread
Perinephric Fat, Lungs, Bone, Lymph Nodes
2242
Uncommon benign epithelial neoplasms arising from intercalated cells of CD
Oncocytoma
2243
Why do CCC's appear cystic
Liquefactive necrosis
2244
MET mutation
Genetics of Papillary RCC
2245
Oncocytoma
Uncommon benign epithelial neoplasms arising from intercalated cells of CD
2246
Papillary Renal Cell Carcinoma
Short nipple-like or long finger-like projections of tumor cells in fibrovascular stalk
2247
Mahogony Brown kidney mass
Oncocytoma
2248
Wilm's tumor is composed, microscopically, of
a mixture of cellular elements: blastemal, stromal, epithelial
2249
Very common, look just like renal papillary carcinomas under microscope
Small renal cortical papillary neoplasms
2250
What causes "empty" appearance of CCC on US
Liquefaction
2251
What is helpful to radiologists in dx oncocytoma
Central Stellate Scar
2252
vHL mutations
Clear Cell Renal Carcinoma
2253
Small round blue cells, abortive tubules or glomeruli, fibroblastic stromal cells, and anaplastic cells
Wilms Tumor is composed of
2254
Which subtype of Renal Cell Carcinoma has best prognosis
Chromophobe (aneuploidy)
2255
Beckwith-Wiedemann Syndrome is associated with
loss of genetic imprinting that normally silences allele controlling ILGF2
2256
Most common presentation of Wilms tumor
Abdominal mass
2257
Clear Cell Carcinoma cells may form
Abortive Tubules
2258
Small renal cortical papillary neoplasms
Very common, look just like renal papillary carcinomas under microscope
2259
Grossly mahagony brown w/ central stellate scar
Oncocytoma
2260
Wilms Tumor is composed of
Small round blue cells, abortive tubules or glomeruli, fibroblastic stromal cells, and anaplastic cells
2261
Activating mutations in MET --> TKR for HGF
Papillary Renal Cell Carcinoma is associated with what mutations
2262
Mutations in Clear Cell Carcinoma and consequence
vHL -> excess HIFs lead to excess VEGF
2263
Clear Cell Carcinoma is composed of cells with ____ corrleated with ___ apparent grossly
Vacuolated (lipid-laden) cytoplasm, correlated with yellow color grossly
2264
Short nipple-like or long finger-like projections of tumor cells in fibrovascular stalk
Papillary Renal Cell Carcinoma
2265
Why does CCC have delicate vascular network
VEGF/vHL
2266
Second and Third Most common types of Renal Cell Carcinoma
Papillary and then Chromophobe
2267
Malignant neoplasm composed of cells with clear or eosinophilic cytoplasm w/in delicated vascular network
Clear Cell RC
2268
Central Stellate Scar
Oncocytoma
2269
Papillary Renal Cell Carcinoma is associated with what mutations
Activating mutations in MET --> TKR for HGF
2270
Acquired dialysis related renal cystic disease
60% clear/ 40% papillary
2271
Positive for Hale's colloidal iron stain
Chromophobe Carcinoma
2272
First and Second most frequent presenting symptom of RCC
Hematuria, Dull Flank Pain
