Quiz 1 Flashcards
1
Q
How does the kidney act as an endocrine organ
A
Secreted erythropoietin, renin and prostaglandins and regulates vitamins D metabolism
2
Q
What is the mechanism of most glomerular vs tubular and interstitial diseases
A
Tubular is usually immune mediated, tubular and interstitial are usually toxic or infectious
3
Q
What is azotemia
A
Elevation of BUN and creatinine levels; related to decreased GFR; feature of acute and chronic injury
4
Q
What is prerenal azotemia
A
Hypoperfusion of kidneys that impairs renal function in absence of parenhcymal damage
5
Q
What is postrenal azotemia
A
Whenever urine flow is obstructed distal to kidney; relief of obstruction corrects the azotemia
6
Q
What is uremia
A
When azotemia becomes associated with a constellation of clinical signs and sx; frequently manifest secondary involvement of GI (uremic gastroenteritis), peripheral nerves and heart (uremic fibrinous pericarditis)
7
Q
What is nephritic syndrome
A
Caused by glomerular dz; dominated by acute onset of either grossly visible hematuria or microscopic hematuria (dysmorphic red cells and red cast cells on urinalysis), diminished GFT, proteinuria and HTN *classic presentation of poststrep glomerulonephritis
8
Q
What is rapidly progressive glomerulonephritis
A
Nephritic syndrome with rapid decline in GFR (within hours to days)
9
Q
What is nephrotic syndrome
A
Due to glomerular dz; heavy proteinuria (more than 3.5 gm/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria
10
Q
What is asymptomatic hematuria or proteinuria usually a manifestation of
A
Subtle or mild glomerular abnormalities
11
Q
What is acute kidney injury
A
Rapid decline in GFT with dysregulation of fluid and electrolyte balance and retention of met waste product (urea and creatinine); *most severe form -> oliguria or anuria (reduced or no pee); * can result from glomerular, interstitial, vascular, or acute tubular injury
12
Q
What is chronic kidney dz.
A
Presence of diminished GFR less than 60 mL/min for at least 3 months from any cause, and/or persistent albuminuria
13
Q
What is the GFR of ESRD
A
Less than 5% of normal; terminal stage of uremia
14
Q
What are the characteristics of renal tubular defects
A
Dominated by polyuria, nocturia, and electrolyte disorders; results of dz that directly affects tubular structures (nephronophthisis medullary cystic dz) or cause defects in specific tubular fxns (can be inherited - familial nephrogenic diabetes, cystinuria, renal tubular acidosis) or acquired (lead nephropathy)
15
Q
What are the clinical manifestations of urinary tract obstruction and renal tumors
A
Varied based on location; UTI -> bactetriuria and pyuria (bacteria and leukocytes in urine)
16
Q
What are secondary glomerular dz
A
Glomerular damage caused by other diseases
17
Q
What is primary glomerulonephritis or glomerulopathy
A
When kidney is only or predominant organ involved
18
Q
What are the fluid and electrolyte systemic manifestations of chronic kidney dz
A
Dehydration, edema, hyperkalemia, met acidosis
19
Q
What are the calcium phosphate and bone systemic manifestations of chronic kidney dz
A
Hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism, Renal osteodystrophy
20
Q
What are the hematologic systemic manifestations of chronic kidney dz
A
Anemia, bleeding diarrhea is
21
Q
What are the cardiopulm systemic manifestations of chronic kidney dz
A
HTN, CHF, cardiomyopathy, pulm edema, uremic pericarditis
22
Q
What are the GI systemic manifestations of chronic kidney dz
A
N/V, bleeding, esophagitis, gastritis, colitis
23
Q
What are the neuromuscular systemic manifestations of chronic kidney dz
A
Myopathy, peripheral neuropathy, encephalopathy
24
Q
What are the dermatologic systemic manifestations of chronic kidney dz
A
Sallow color, Pruritus, dermatitis
25
What are the primary glomerulopathies
Acute proliferative glomerulonephritis, rapidly progressive, membranous nephropathy, minimal change dz, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, dense deposit dz, IgA nephropathy, chronic glomerulonephritis
26
What are the systemic dz with glomerular involvement
SLE, DM, amyloidosis, goodpasture syndrome, microscopic polyarteritis/polyangiitis, wegener granulomatosis, henoch-schonlein purpura, bacterial endocarditis
27
What are the hereditary glomerular diseases
Alport syndrome, thin basement membrane dz, fabry dz
28
What does the glomerular capillary wall consist of
- fenestrated endothelial cells
- glomerular basement membrane (GBM) with a thick lamina densa and thinner (lamina rara interna/externa); NC1 domain important for assembly of collagen into BM (target of abs in anti-GBM nephritis); alpha chain defects -> hereditary nephritis
- visceral epithelial cells (podocytes)- adhere to lamina rara externa
- supported by mesangial cells between capillaries; impt in forms of glomerulonephritis
29
What is the glomerulus permeable to
Water, small solutes; impermeable to proteins the size of albumin or larger ; more cationic -> more permeable
30
What is the visceral epithelial cell important for
Maintenance of glomerular barrier function; its slit diaphragm presents a size-selective distal diffusion barrier to filtration of proteins and is responsible for synthesis of GBM components
31
What is nephrin
Transmembrane protein with a large extracellular portion made up of Ig-like domain; extend toward each other and dimerzie across the slit diaphragm; form connections with podocin, CD2-assoc protein and actin cytoskeleton of podocytes
32
What do mutations in slit diaphragm proteins lead to
Nephrotic syndrome
33
What are the glomerular syndromes
- nephritic: hematuria, azotemia, variable proteinuria, oliguria, edema, HTN
- rapidly progressive glomerulonephritis: acute nephritis, proteinuria, acute renal failure
- nephrotic syndrome: proteinuria (>3.5), hypoalbuminemia, hyperlipidemia, lipiduria
- chronic renal failure: azotemia -> uremia progressive for months to years
- isolated urinary abnormalities: glomerular hematuria and/or subnephrotic proteinuria
34
What causes hypercellularity of the glomerular tufts
- proliferation of mesangial or endothelial cells
- infiltration of leukocytes -> referred to as endocapillary proliferation
- formation of crescents: accumulations of cells composed of proliferating glomerular epithelial cells and infiltrating leukocytes; occurs following immune/inflammatory injury involving cap walls; plasma proteins leak into urinary space where exposure to procoagulants lead to fibrin deposition; activation of coagulation factors is trigger for crescent formation
35
What is hyalinosis
Accumulation of material that is homogenous and eosinophilic by light micro; hyalin is composed of plasma proteins that have insulated from circulation into glomerular structures; can obliterate cap lumens; usually a consequence of endothelial or cap wall injury and end result of glomerular damage
36
What is sclerosis
Deposition of collagenous matrix; can be confined to mesangial areas (DM) or involve cap loops; can result in obliteration of cap
37
What are the types of primary glomerulopathies
Diffuse: involving all of glomeruli
Global: involving the entirety of the individual glomeruli
Focal: involving only a fraction of glomeruli
Segmental: affecting a part of each glomerulus
Cap loop or mesangial: affecting predominantly cap or mesangial regions
38
What is the classic example of glomerular injury resulting from local formation of immune complexes (abs reacting to antigens on glomerulus)
Membraneous nephropathy
39
What antigen underlies most cases of primary human membranous nephropathy
M-type phospholipase A2 receptor (PLA2R): ab that bind to this leads to complement activation and shedding of immune aggregates from the cell surface to form characteristic deposits of immune complexes along the subepithelial aspect of the BM
40
What is the pattern of immune deposition on immunofluorescent microscopy of membranous nephropathy
Granular rather than linear; reflective of very localized antigen-ab reaction; on light microscopy, BM looks thickened
41
What are the thiazides diuretics and what are they used to treat
Hydrochlorothiazide, metolazone, chlorthalidone; HTN and edema
42
What are the K+ sparing diuretics and what are they used to treat
Na+ channel blockers: amiloride and triamterene
Aldosterone antagonist: spirinolactone and eplerenone
-edema and HTN
43
What are the carbonic anhydrase inhibitors and what are they used to treat
Acetazolamide; urinary alkalization, mountain sickness, glaucoma
44
What are the loops diuretics and what are they used to treat
Furosemide, torsemide, bumetanide, ethacrynic acid; edema and HTN
45
What are the aquaretics and what are they used to treat
Conivaptan and tolvaptan; hyponatremia
46
What is the osmotic diuretic and what is it used to treat
Mannitol; maintains urine flow
47
What is a natriuretic
Substance that promotes excretion of sodium
48
Which diuretics work on the proximal tubule
Osmotic and carbonic anhydrase inhibitors
49
Which diuretics work on the thin descending loop of Henle
Osmotic diuretics
50
Which diuretics work on the thick ascending loop of henle
Loop diuretics
51
Which diuretics work on the distal convoluted tubule
Thiazides
52
Which diuretics work on the cortical collecting duct
Sodium channel blockers and spironolactone
53
Which diuretics work on the collecting duct
Vaptans
54
What is the MOA of thiazides
Sodium chloride channel blocker
55
What is the MOA of loop diuretics
Sodium, potassium, 2 chloride blocker
56
Where do the K+ sparing drugs work
Late distal convoluted tubule and collecting duct
57
What are the effects of K on the heart
Tall t waves, prolonged PR interval, widened QRS interval, flattened P waves, bradycardia, V tach/fib; sinus arrest or nodal rhythm
58
What are the effects of hypokalemia on the heart
Flattened T waves, ST depression, prolonged QT interval, tall U waves, atrial Arrhythmias, v tach/fib
59
Which diuretics contain sulfa
Loop, thiazides
60
Which diuretics have the greatest amount of diuretic effect
Loop
61
What is the MOA of furosemide
Directly inhibits reabosorption of sodium and chloride; indirectly inhibits reabsoprtion of calcium and magnesium; causes increased excretion of water, sodium, potassium, chloride, magnesium and calcium
62
What is furosemide given to treat
Edema assoc with heart failure, hep dz, renal dz; acute pulm edema -> decreases preload; causes rapid dyspnea relief; HTN -> works in patients with low GFR
63
What toxicities are associated with furosemide
Hypokalemia, hyponatremia, hypocalcemia(kidney stones), hypomagnesemia, hypochloremic metabolic alkalosis, hyperglycemia, hyperuricemia (gout), increased chol and triglycerides (atherosclerosis), ototoxicity, hypersensitivity b/c sulfa, dangerous during pregnancy
64
What are the characteristics of torsemide, bumetanide, ethacrynic acid
Torsemide: longer 1/2 life and better oral absorption than furosemide
Bumetanide: more predictable oral absorption
Ethacrynic acid: *non-sulfonamide loop diuretic reserved for those with sulfa allergy
65
What kind of urine is produced with loop diuretics
Isotonic
66
What forms are available for loop diuretics
PO, IV, IM
67
What drug interactions do loop diuretics hav e
- digoxin
- ototoxic drugs (gentamicin)
- potassium-sparing diuretics can counterbalance potassium wasting effects
- *increases lithium toxicity
68
Which diuretics cause the greatest sodium loss
Loop
69
What are the effects of hydrochlorothiazide
Increases urinary excretion of sodium and water, potassium and magnesium
70
What are the clinical applications of HCTZ
Management of mild-moderate HTN *no effect in patients with low GFR; edema; calcium nephrolithiasis (causes decrease in excretion of calcium) and nephrogenic diabetes insipidus
71
What toxicities are assoc with HCTZ
Orthostatic hypotension, hypokalemia, hypomagnesemia, hyponatremia, hypochloremic met alkalosis, hypercalcemia, hyperglycemia, hyperuricemia, sulf drug hypersensitivity
72
What are the characteristcis of chlorothiazide, chlorthalidone, metolazone
Chlorothiazide: poor oral absorption
Chlorthalidone: longer half life
Metolazone: long acting; CHF
73
Why do thiazides cause more calcium absorption
More reabsopriton in prox tubule because of volume contraction
74
Is the loss of magnesium greater in loop or thiazides
Thiazides
75
What kind of urine does thiazides produce
Dilute
76
Which diuretic causes the greatest bicarbonate loss
Thiazides; impairs distal nephron H+ secretion
77
When should you not take thiazides diuretics (what time of day)
Bedtime
78
What drug interactions do thiazides have
Increases digoxin and lithium toxicity
79
Which thiazide is used more to reduce CV morbidity and mortality when used for tx of HTN
Chlorthalidone: more potent and longer lasting
80
What are the effects of amiloride
Small increase in sodium excretion; blocks major pathway for potassium elimination so K retained; indirectly decreases H, magnesium, and Ca excretion
81
What are the clinical applications of amiloride
Counteracts potassium loss induced by other diuretics in tx of HTN or heart failure; ascites, pediatric HTN
82
What toxicities are associated with amiloride
Hyperkalemia, hyponatremia, hypovolemia, Hyperchloremic metabolic acidosis, dizziness, N/V
83
What are the effects of spironolactone
Blunt as ability of aldosterone to promote Na K exchange in collecting duct by decreasing Na entry through luminal Na channels, decreased basolateral N/K ATPase
84
What are the clinical applications of spironolactone
Counteracts K loss by other diuretics; treatment of primary hyperaldosteronism; reduces fibrosis post MI heart failure; hirsutism; treatment of androgenic alopecia in females
85
What toxicities are associated with spironolactone
Hyperkalemia, amenorrhea, hirsutism, gynecomastia, impotence; tumorigen
86
What is eplerenone
More selective aldosterone antagonist; approved for use in post-MI heart failure
87
What is the onset of action for spironolactone
48 hrs
88
What are the aquaretics
Vaptans
89
What is the MOA of vaptans
Block ADH receptor in collecting duct *non-peptide vasopressin receptor antagonist
90
What are the clinical applications of conivaptan
Treatment of euvolemic and hypervolemic hyponatremia in patients who are hospitalized, symptomatic, not responsive to fluid restriction; *monitor sodium bc too rapid sodium correction -> osmotic demyelination; AD polyistic kidney dz
91
How is conivaptan administered
IV; *substrate of CYP3A4 so inducers and inhibitors of concern; eliminated in feces
92
What toxicities are associated with conivaptan
Orthostatic hypotension, thirst, polyuria, bedwetting
93
What are the characteristics of tolvaptan
Selective V2 receptor antagonist administered orally; *only in hospital; must use 30 days; longer use can be fatal (hepatotoxic)
94
How do carbonic anhydrase inhibitors work
Bicarbonate ion remains in early prox tubule, H+ cycling lost, inhibiting Na/H exchange -> leads to sodium bicarbonate diuretics and hyperchloremic acidosis
95
What are the uses for carbonic anhydrase inhibitors
Urinary alkalinization, metabolic alkalosis, glaucoma, acute mountain sickness
96
What are the adverse effects of carbonic anhydrase inhibitors
Hyperchloremic metabolic acidosis, nephrolithiasis, potassium wasting
97
How do you administer mannitol
IV in large amounts to raise osmolality (in grams)
98
What are the adverse effects of osmotic diuretics
ECV is acutely increased which can exacebate heart failure
99
What are the uses of osmotic diuretics
Prophylaxis of renal failure (keeps fluid in tubule), reduction in intracranial pressure,, reduction in intraocular pressure
100
How is licorice a. Diuretic
Contains glycyrrhizic acid which. Potentiates aldosterone effect
101
When do you give HCTZ to someone with cirrhosis.
If ClCr > 50 mL/min;; add to spironolactone.
102
If lithium is the. Cause of DI, what do you treat. It with
Amiloride
103
What are planted antigens
Cationic molecules that bind to an ionic components of the glomerulus, DNA, nucleosides, bacterial products, large aggregated proteins
104
What is an example of a planted antigen causing membranous nephropathy
Infants fed cow milk
105
What pattern does anti-GBM antibody induced glomerulonephritis cause on imunofluorescence
Linear
106
What is goodpasture syndrome
When anti-GBM abs cross react with lung alveoli
107
What is the GBM antigen responsible for classic anti-GBM ab induced glomerulonephritis and goodpasture syndrome
NC1 and alpha 3 chain of type IV collagen
108
What microbial antigens have beeen implicated in glomerulonephritis resulting from deposition of circulating immune complexes
Strep, surface antigen of hep B, C, and trep pallium, plasmodium falciparum
109
What do immune complex formation glomerulonephritis look like on immunofluorescence
Granular
110
What affects the glomerular localization of the antigen, ab or immune complexes
-molecular charge and size of reactants: highly cationic antigens tend to cross GBM and reside in subepithelial location; anionic -> subendothelialy and or NOT nephritogenic at all; neutral charge and immune complexes accumulate in mesangium; large immune complexes not nephritogenic because cleared by macrophages and do not enter GBM
111
What does the location of the ab, antigen, complexes usually indicate about the pathology
- in subendothelial and mesangial -> inflammatory pathology
| - subepithelial: non-inflammatory
112
What are epimembranous deposits indicative of
Membranous nephropathy and heymann nephritis
113
What conditions would you see subendothelial deposits in
SLE and membranoproliferative glomerulonephritis
114
Where would you see deposits with IgA nephropathy
Mesangial
115
When does activation of the alternative complement pathway occur
In dense-deposit dz (membranoproliferative glomerulonephritis - MPGN type II) and in C3 glomerulopathies
116
What are the activities of neutrophils in glomerular injury
Release proteases which cause GBM degradation, ROS, and arachnids is acid which contribute to reductions in GFR
117
What is the role of resident glomerular cells in inflammatory reactions
Cause be stimulated to produce ROS, cytokines, chemokines, growth factors, eicosanoids, NO, and endothelin
118
What makes up the membrane attack complex and what is its function in kidney inflammatory reaction
C5b-C9 -> cell lysis. And simulates mesangial cell to produce oxidants, proteases *even in the absence of neutrophils, C5b-9 can cause proteinuria
119
What is podocytopathy
Injury to podocytes (can be caused by HIV)
120
What diseases can cause loss of podocytes
Focal and segmental glomerulosclerosis and diabetic nephropathy
121
What is normally the key event in causing proteinuria
Injury to slit diaphragms (mediated injury or mutation in podocin or nephrin)
122
What does the GFR have to be reduced to for progression to ESRD to inevitably occur
30-50% of normal
123
What is focal segmental glomerulosclerosis
Progressive fibrosis involving portions of some glomeruli develops after many types of renal injury and leads to proteinuria and increasing impairment; can occur even when primary dz was nonglomerular; initiated by adaptive change of the glomeruli; compensatory hypertrophy of remaining glomeruli can maintain function but proteinuria an segmental glomerulosclerosis soon develops; assoc w/ hemodynamic changes (increase in blood flow, filtration and transcap pressure)
124
What is used to treat progression of glomerulosclerosis
Inhibits of renin-angiotensin system
125
What is tubulointersitial fibrosis
*better correlation with decline in renal function with extent of tubulointerstitial damage than with severity of glomerular injury ; causes of tubulointersitital injury - ischemia of tubule segments downstream from sclerotic glomeruli, damage of peritubular cap blood supply, *proteinuria can cause direct injury to and activation of tubular cells which express adhesion molecules and elaborate cytokines that lead to fibrosis
126
What is nephritic syndrome
Glomerular dz characterized by inflammation in glomeruli; *usually presents with hematuria, red cell casts in urine, azotemia, oliguria, and mild-moderate HTN (can have proteinuria and edema but more severe in nephrotic syndrome); can occur with SLE and microscopic polyangiitis but typically characteristic of acute proliferative and exudative glomerulonephritis and crescentic glomerulonephritis *
127
What is acute proliferative (postinfectious) glomerulonephritis
Cluster of dz characterized by diffuse proliferation of glomerular cells associated with influx (exudate) of leukocytes; typically caused by immune complexes
128
What is post strep glomerulonephritis
Occurs after strep infection of pharynx or skin (impetigo); only strep A (most common types 12,4,1); serum complement levels low; granular immune complexes in glomeruli; antigen responsible is SpeB (pyogenic exotoxin); *hump like deposits in subendothelial locations that can dissociate, migrate across GBM and reform on subepithelial side
129
What is the most frequent presentation of postinfectious glomerulonephritis
Nephritic syndrome
130
What does postinfectious look like on fluorescence
Granular IgG and C3 in GBM and mesangium; granular IgA in some cases
131
What is the most frequent clinical presentation of goodpasture syndrome
Rapidly progressive glomerulonephritis
132
What is the pathogenesis of goodpasture
anti-GBM COL4-A3
133
What is seen on light and fluorescent microscopy for goodpasture
Light: extracapillary proliferation with crescents; necrosis
FLuorescence: linear IgG and C3; fibrin in crescents
134
What is seen on light microscopy for chronic glomerulonephritis
Hyalinized glomeruli
135
What is the most frequent presentation of membranous nephropathy
Nephrotic syndrome
136
What is seen on light microscopy for membranous nephropathy
Diffuse cap wall thickening
137
What is the most frequent presentation of minimal change dz
Nephrotic syndrome; unknown pathogenesis - podocytes injury
138
What is seen on light microscopy of minimal change dz
Normal; lipid in tubules
139
What is the most common presentation of focal segmental glomerulosclerosis
Nephrotic syndrome nonnephrotic proteinuria
140
what does dense-deposit dz (MPGN type II) present as
Hematuria; chronic renal failure; autoab -> alternative complement pathway
141
What does dense-deposit dz look like on fluorescence micro
C3 no C1q or C4
142
What does IgA nephropathy usually present as
Recurrent hematuria or proteinuria; unknown path
143
What does IgA nephropathy look like on light micro
Focal mesangial proliferative glomerulonephritis; mesangial widening
144
What is the morphology of post strep glomerulonephritis
Enlarges hypercellular glomeruli caused by neutrophil and monocytes recruitment, proliferation of mesangial and endothelial cells and crescent formation; involves all lobes of glomeruli
145
What is the clinical presentation of post strep glomerulonephritis
Hematuria post sore throat; periorbital edema and some HTN in kids; in adults its more likely to be atypical (sudden appearance of HTN or edema with elevation in BUN)
146
What is the tx for post strep glomerulonephritis
Maintaining sodium and water balance
147
What is assoc with an unfavorable prognosis of post strep glomerulonephritis
Heavy proteinuria with ab GFR
148
What other infections cause postinfectious glomerulonephritis
Staph endocarditis (sometimes produces IgA rather than IgG immune deposits), pneumococcal pneumonia, meningococcemia, hep B and C, mumps, HIV, varicella, mono, malaria, toxoplasmosis
149
What is rapidly progressive (crescentic) glomerulonephritis
Associated with severe glomerular injury but does not denote a specific etiology form; rapid loss of renal fxn with severe oliguria and signs of nephritis syndrome; death can occur within weeks to months if untreated; histo* crescents in glomeruli (proliferation of parietal epithelial cells lining Bowman’s)
150
What causes rapidly progressive glomerulonephritis (RPGN)
Immuno mediated
151
What types is RPGN broken down into
- anti-GMB ab mediated dz; linear deposits of IgG and C3 in GBM; can cross react and cause goodpasture; plasmapheresis for tx; high prevalence of ppl affected have HLA-DRB1
- immune complex deposition: postinfectious, lupus, IgA, and henoch-schonlein purpura; granular pattern; plasmapharesis doesn’t help
- pauci-immune RPGN: lack of anti-GBM abs or immune complexes by fluorescence and EM; have circulating antineutrophil cytoplasmic ab (ANCA) and produce cytoplasmic or perinuclear staining pattern -> vasculitides; can be a part of wegener granulomatosis; most often idiopathic
152
What is the morphology of RPGN
Kidneys enlarged and pale with petechial hemorrhage; crescents; fibrin btw cellular layers in the crescents; EM: ruptures in GBM
153
What is the clinical manifestation of RPGN
Hematuria with RBC casts, moderate proteinuria, variable HTN and edema; in goodpasture, dominated by recurrent hemoptysis or pulmonary hemorrhage; many patients require dialysis or transplant over time
154
What is the path of nephrotic syndrome
Caused by derangement in glomerular cap walls resulting in increased permeability to plasma proteins -> massive proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia and lipiduria
155
What causes the edema in nephrotic syndrome
Reduced intravascualr colloid osmotic pressure; also retention of sodium and water due to compensatory secretion of aldosterone mediated by hpovolemia enhanced renin secretion and reduction in secretion of atrial peptides
156
What is a highly selective vs poorly selective proteinuria
Highly: low weight proteins (albumin, transferrin)
Poorly: higher weight globulins and albumin
157
How does the lipid appear in the urine of people with nephrotic syndrome
Free fat or oval fat bodies (lipoprotein resorted. By tubular epithelial cells and then shed along with injured tubular cells)
158
What are nephrotic patients vulnerable to
Infection especially staph and pneumococcal b/c loss of Igs in urine; thrombotic and thromboembolic complications also common (loss of anticoagulants); renal v thrombosis is consequence particularly in membranous nephropathy
159
What is nephrotic syndrome caused by in the US in diff ages
Younger than 17: primary kidney lesion
| Adults:systemic dx
160
What are the most frequent systemic causes of nephrotic syndrome
Diabetes, amyloidosis, SLE; also caused by drugs(NSAIDs, penicillamine and heroin), infections, malignancy (carcinoma, lymnphoma) and bee sting allergies, hereditary nephritis
161
What are the most common primary lesions of the kidney that cause nephrotic syndrome
Minimal change dz (most common in kids), membranous glomerulopathy(most common in older adults), and focal segmental glomerulosclerosis
162
What are the most common causes of secondary membranous nephropathy
- drugs: penicillamine, gold, NSAIDs (esp in RA patients)
- malignant tumors (carcinomas of lug and colon and melanoma)
- SLE
- infections :hep b,c, syphilis, schisto, malaria
163
What antigen is implicated in neonatal membraneous nephropathy
Endopeptidase
164
What HLA is membranous nephropathy linked to
HLA-DQA1; caused by abs to renal autoantigen mostly phospholipase A2 receptor
165
What is the main Ig deposited in membranous nephropathy
IgG4
166
What do you see on silver stain with membranous nephropathy
Spikes from GBM
167
what is the major determinant of ECF osmolality
Sodium
168
How can you estimate ECF osmolality
Doubling sodium concentration
169
Differences in what pressure cause movement of fluid btw ICF and ECF
Only osmotic
170
What is the formula for starling forces
Pc-Pi - osmotic cap - osmotic interstitial
171
What happens when you add hypotonic NaCl to ECF
Osmolities of ECF and ICF lower and volume of both increased
172
What happens when you add hypertonic NaCl to ECF
Osmolalities of ICF and ECF increase; volume of ECF increases by ICF decreases
173
How do you calculate anion gap
Sodium - (chloride + bicarbonate)
174
What is the effect of vasocontrictors (symp, angiotensin II, and endothelin on GFR)
Decreases
175
What is the effect of vasodilators on the GFR
- prostaglandins: no change/increase
- NO: increase
- bradykinin: increase
176
What is the effect of ANP/BNP on GRF
Increases it; no change on RBF
177
Where are the alpha 1 receptors in the kidney
Afferent arterioles
178
What is the effect of sympathetic stimulation on the kidney
Decreases hydrostatic pressure and GFR decreases salt excretion
179
How is renin stimulated
By beta receptor stimulation
180
What is the most effected part of the kidney by sympathetic
Proximal tubule
181
What signals do the kidneys receive in response to volume expansion
Decreases sympathetic, increased ANP BNP, inhibition of ADH, decreased renin and aldosterone
* increased excretion of sodium
182
What factors are important for renin secretion
Perfusion pressure sympathetic n activity and delivery of NaCl to macula densa
183
What are the functions of angiotensin II
Stimulation of aldosterone, arterial vasoconstriction, stimulates ADH and thirst, enhances NaCl reabsorption
184
How does aldosterone work
Reduces NaCl excretion by stimulating its reabsorption by thick ascending loop, distal tubule and collecting duct; increases number of NaCl synporters and Na channels in principle cells in late distal tubule and collecting duct and Na/k pump on basolateral side , stimulates H secretion through H ATPase in apical membrane of alpha intercalated cells
185
How is Na absorbed in first half of proximal tubule
With bicarbonate, in second half absorbed with Cl
186
Which part of the loop of henle absorbs Na
Only ascending
187
Which part of the loop of henle is impermeable to water
Ascending
188
What does th early distal tubule reabsorb
Na Cl via NCC symporter and ca , impermeable to water * thiazides
189
Does the proteinuria in membranous nephropathy respond well to corticosteroids
no
190
what is minimal change dz
relatively benign; diffuse effacement of foot processes of visceral epithelial cells *detectable only by EM in glomeruli that appear normal via light micro; *most frequent cause of nephrotic syndrome in children
191
People with what disease are at increased risk for minimal change dz
non-hodgkins lymphoma
192
does the proteinuria of minimal change dz respond to corticosteroids
yes
193
what are the clinical features of minimal change dz
renal fxn remains good; massive proteinuria; no HTN or hematuria; *characteristic is dramatic repsonse to corticosteroids
194
what is primary focal segmental glomerulosclerosis
most common cause of nephrotic syndrome in adults; HTN and hematuria with proteinuria
195
what are the classification and types of focal segmental glomerulosclerosis
- primary dz
- in association with HIV, heroin addiction, sickle cell or obesity
- as a secondary event
- component of adaptive response to loss of renal tissue (unilateral renal agensis or acquired causes)
- uncommon inherited forms; mutations in genes encoding for slit diaphragm
196
how does focal segmental glomerulosclerosis differ from minimal change disease
in FSGS - higher hematuria, reduced GFR and HTN; proteinuria is nonselective; poor response to corticosteroids; progression to kidney dz with ESRD
197
what is the hallmark of the pathogenesis of FSGS
damage of epithlial cells; hyalinosis and sclerosis occur from entrapment of plasma proteins in hyperpermeable foci and increased ECM deposition
198
what is the genetic basis for FSGS
- NPHS1 on chrom 19q13 encodes nephrin
- AR FSGS - caused by mutations in NPHS2 which encodes podocin *steroid resistant nephrotic syndrome of childhood onset
- AD caused by mutation in alpha actinin 4 (encodes podocyte binding protein)
- TRPC6 -> increases calcium influx into podocytes
199
People of african descent with what mutation are at risk for FSGS
APOL1
200
what is collapsing glomerulopathy
variant of FSGS; characterized by collapse of entire glomerular tuft with or w/o FSGS lesions; characteristic feature is proliferation and hypertrophy of glomerular visceral epithilal cells *most characteristic lesion of HIV nephropathy = poor prognosis (more common in blacks)
201
what are the morphologic features of HIV associated nephropathy
collapsing variant of FSGS; striking focal cystic dilation of tubule segments filled with proteins; tubuloreticular inclusions within endothelial cells (EM) -> modification of ER induced by circulating IFNa
202
what is membranoproliferative glomerulonephritis type I and II
type I: deposition of immune complexes containing IgG and complement
type II: dense deposit dz; activation of complement is most impt factor; belongs to group of disorders called C3 glomerulopathies
203
what are membranoproliferative glomerulonephritis also called
mesangiocapillary glomeruloneprhtiis (because proflieration is mostly in mesangium)
204
what is the morphology of MPGN
glomeruli are large and hypercellular; glomeruli have lobular appearacne due to proflierating mesangial cells and increased mesangial matrix; GBM is thickened and shows double contour or tram track appearance (in silver or PAS stains) caused by duplication of BM
*type I characterized by subendothelial electron dense deposits IgG and C3 deposited in granular pattern
205
what are the clinical features of MPGN
most present with nephrotic syndrome and a component of nephritic syndrome (hematuria); not improved by any treatment
206
how do you calculate interstitial fluid levels
ECF-plasma
207
what are normal sodium levels
136-146
208
in what type of patient would you be careful administering NSAIDS in terms of kidney
HTN, renal steonsis, patient on diuretics; NSAIDS will inhibit prostaglandin production
209
what does vasodilation of the afferent artieriole cause
increased RBF, GFR and hydrostatic pressure; caused by prostaglandins, bradykinin, NO, dopamine, ANP
210
what does vasoconstriction of the afferent arteriole cause
decrease in RBF, GFR, and hydrostatic pressure
211
what does vasodilation of the efferent arteriole cause
increase in RBF, decrease in GFR, increase in hydrostatic pressure
212
what does vasoconstriction of the efferent arteriole cause
decreased RBF, increased GFR, decreased hydrostatic pressure
213
what leads to renin secretion
symp stimulation, decreased NaCl to macula densa, vasoconstriction of afferent arteriole
214
what inhibits renin
angiotensin II and ADH
215
what does ang II do
increase thirst, increase Na reabsorption in PT; increase ADH and aldosterone
216
what do principle cells do
sodium and water reabsorption and potassium secretion
217
which hormones regulate water permeability
ADH ANP BNP in late distal tubule and collecting duct
218
what causes a decrease in ADH
ethanol
219
what causes secondary MPGN
SLE, hep B and C; endocarditis; HIV; schisto; alpha antitrypsin deficiency; malignant dz; Type I
220
what causes dense deposit dz
excess activation of alternative complement pathway; decreased C3 but normal C1 and 4; low factor B and properdin (alternative pathway); C3 and properdin deposited in glomeruli but no IgG; C3 nephritic factor (C3NeF) binds C3 convertase and protects it from inactivation
221
what is the morphology of dense deposit dz
characterstic on EM -> permeation of lamina densa of GBM by ribbon-like electron dense material; C3 not in dense deposits, but in BM and mesangium (mesangial rings)
222
what are the clinical features of dense deposit disease
primarily affects kids and young adults; mixed nephritic and nephrotic; poor prognosis; recurrence in transplant
223
what is IgA nephropathy (berger dz)
presence of promiment IgA deposits in mesangial regions; recurrent hematuria *most common type of glomerulonephritis worldwide; normally isolated dz but can present in a systemic disorder of children (henoch schnolein purpura); secondary IgA neprhopathy in liver nad intestinal dz
224
what is the pathogenesis of IgA nephropathy
defect in normal formation or attachment of galactose-containing sugar chains called O-linked glycans to the hinge region of IgA -> aberrently glycosylated IgA1 deposited in glomeruli or forms comlexes with IgG abs and deposit in mesangium; can activate complement via alternative pathway (C3 no C1q or C4)
225
what diseases are associated with an increased risk of IgA nephropathy
Celiac, liver dz (defective clearance of IgA complexes)
226
what is the classic immunofluorescent picture of IgA nephropathy
IgA in mesangium
227
what are the clinical features of IgA nephropathy
hematuria lasting for several days and then returns; slow progression to renal failure (increased risk of progression -> proteinuria, HTRN and extent of glomerulosclerosis); recurrence in transplant
228
what is hereditary nephritis
group of familial renal diseases assoc with mutations in collagen genes that manifest primarily with glomerular injury *alport syndrome and thin basement membrane lesion (benign familial hematuria)
229
what is alport syndrome
hematuria with progression to chronic renal failure accompanied by nerve deafness and various eye disorders (lens dislocation, posterior cataracts and corneal dystrophy) *X-linked (males- fully syndrome; femalse - hematuria) but also AR
230
what is the pathogenesis of alport syndrome
mutations in collagen IV; mutations in collagen IV alpha 5 chain (COL4A5) assoc with ESRD at earlier age
231
what is the morphology of alport syndrome
EM - irregular foci of thickening alternating with thinning and splitting and lamination of lamina densa = prodcues basket weave appearance
232
what are the clinical features of alport syndrome
gross or microscopic hematuria; proteinuria can develop later
233
what is thin basement membrane lesion or benign familial hematuria
common; manifested by asymptomatic hematuria; diffuse thinning of GBM; excellent prognosis; caused by mutations in alpha 3 or 4 chains of collagen IV; AD or AR
234
does chronic glomerulonephritis have to come from an acute phase
no
235
what is the morphology of chronic glomerulonephritis
kidneys are symmetrically contracted and have granular cortical surfaces; cortex is thinned and incrase in peripelvic fat
236
what is henoch schonlein purpura
childhood syndrome consisting of pupuric skin lesions (extensor surfaces and butt), ab pain and intestinal bleeding and arthralgias with renal abnormalities (hematuria, nephritic/nephrotic syndrome); onset often follows resp infection; excellent prognsosis
237
what is the pathognomoinc feature of henoch schonlein purpura
deposition of IgA and sometimes IgG and C3 in mesangial region
238
what is fibrillary glomerulonephritis
fibrillar deposits in mesangium and capillary walls that resemble amyloid but do not stain with congo red; deposition of IgG (4) C3 and Igk and Iglambda light chains; nephrotic syndrome, hematuria and progressive renal insufficiency
239
what are goodpasture, microscopic polyagiitis, and granulomatosis with polyangiitis all characterized by
foci of glomerular necrosis and crescent formation
240
what is essential mixed cryoglombulinemia
IgG-IgM complexes induce cutaneous vasculitis, synovitis adn proliferative glomerulonephrtiis (MPGN type I) (assoc with Hep C)
241
what causes acute tubular injury
ischemia (ischemic ATI) or direct toxic injury to tubules (neprhotoxic ATI) or combo - mismatched blood transfusions and other hemolytic crises causing hemoglobinuria and skeletal m injuries causing myoglobinuria
242
what are the results of tubule cell injury
increased sodium delivery to distal tubules which incites vasoconstriction via tubuloglomerular feedback; injured cells detach fromm and cause luminal obstruction, increased intratubular pressure, and decreased GFR; can also cause intersitital edema, increased intersistial pressure
243
which portions of the kidney are extremely vulnerable to ischemic and toxic injury
straight portion of proximal tubule and thick ascending limb in renal medulla
244
what is the difference in morphology of ATI caused by mercuric chloride and carbon tetrachloride and ethylene glycol
mercuric: injured cells contain acidophilic inclusions; later become necrotic, are desquamated at the lumen and undergo calcification
carbon tetrachloride: accumulation of neutral lipids in injured cells
ethylene glycol: ballooning and hydropic or vacuolar degeneration of proximal convoluted tubules; calcium oxalate crystals form in tubule lumens
245
what are that patterns of injury in ischemic and toxic ATI
ischemic: patchy necrosis with short lengths damaged; straight proximal tubule and ascending lim most vulnerable
Toxic: extensive necrosis along proximal convoluted tubules
*both types: lumens of distal convoluted tubule and collecting duct contains casts
246
what are the phases of ATI
- initiation: about 36 hrs; slight decline in urine output with rise in BUN
- Maintenance: sustained decrease in urine output, salt and water overload, rising BUN, hyperkalemia, met acidosis, can overcome it
- Recovery: increase in urine volume; hypokalemia becomes a problem; increased vulnerability to infection
247
what are tubulointerstitial nephritis
involves inflammatory injury to tubules and interstitium and manifested by azotemia
248
what are some causes of tubulointersitial nephritis
-acute/chronic bacterial pyelonephritis, acute hypersensitivity, analgesics, heavy metals, lead, cadmium, urate nephropathy, nephrocalcinosis, acute phosphate nephropathy, hypokalemic, oxalate neph, chronic UTI, mutliple myeloma, sjogren, sarcoidsosis, balkan nephropathy, nephronophthisis medullary cystic dz complex
249
what are useful markers in distinguishing acute from chronic tubulointerstitial nephritis
edema , eosinophils and neutrophils in acute form; fibrosis and tubular atrophy in chronic
250
how can tubulointerstitial diseases be distinguished from glomerular disease
-absence of nephritic or nephrotic syndrome; presence of defects in tubular function (can't concentrate urine, metabolic acidosis, etc)
251
what is pyelonephritis
inflammation affecting the tubules, interstitium, and renal pelvis; acute (usually UTI) and chronic(more complex)
252
when is hematogenous spread of infection to the kidneys more likely to occur
in presence of ureteral obstruction and in debilitated patients
253
how do microbes move from the bladder to the kidneys
- urinary tract obstruction: can't flush out microbes; ie: BPH, tumors, stones, or neurogenic gladder dysfunction caused by DM or SC injury
- vesicoureteral reflux: incompetence of vesicoureteral valve
- intrarenal reflux: most common in upper and lower poles of kidney where papillae have flattened or concave tips; demonstrated by voiding cystourethrogram
254
what is acute pyelonephritis
suppurative inflammation of the kidney caused by bacterial or viral (polyomavirus) *histo: intratubular aggregates of neutrophils, tubulitis and tubular necrosis; starts in tubules and can extend to intersititum where it produces abscesses that destroy the tubules; extensive dz can affect glomeruli (esp fungal)
255
what are the 3 complications of acute pyelonephritis
- papillary necrosis: seen mainly in diabetes, sickle cell, and urinary tract obstruction; tips of pyramids have areas of gray-white to yellow necrosis (coagulative)
- pyonephrosis: seen when there is total obstruction; suppurative exudate unable to drain and fils renal pelvis, calcyes and ureter with pus
- perinephric abscess: extension of suppurative inflammation through renal capsule into perinephric tissue
256
what does a pyelonephritic scar suggest
ascending infection and vesicoureteral reflux as the pathogenesis of the dz
257
Who are the most common people to get acute pyelonephritis
catheterized, pregnant women, first year of life (males), females, preexisting renal lesions, DM, immunosuppression
258
The presence of what on urinalysis suggests renal involement
leukocyte casts
259
what is polyomavirus nephropathy
latent infection activated upon immune suppression; chracterized by infection of tubular epithelial cells leading to nuclear enlargmenet and intranuclear inclusions composed of virions in crystalline like lattices on EM; reduce immunosuppression to treat
260
what is chronic pyelonephritis
disorder in which chronic inflammation and scarring involve the calyces and pelvis **only one that does this(**
261
What are the two forms of chronic pyelonephritis
- reflux nephropathy: more common form; occurs early in childhood as a result of superimposition of urinary infection on congenital vesicoureteral reflux and intrarenal reflux
- chronic obstructive pyelonephritis: recurrent infections on obstructive lesions lead to repeated bouts of renal inflammation and scarring
262
what is the morphology of chronic pyelonpehritis
irregularly scarred; if b/l, asymmetric (in glomerulonephritis -> symmetric); coarse discrete corticomedullary scars overlying dilated, blunted, or deformed calcyces and flattened papillae
263
what is xanthogranulomatous pyelonephritis
rare form of chronic pyelonephritis; accumulation of foamy macrophages intermingled with plasma cells, lymphocytes, PMN, and occassional giant cells; associated with proteus infections and obstruction; produce large yellowish orange nodules that can be confused with RCC
264
what is a cause of renal HTN in kids
reflux nephropathy
265
what can some people with pyelonephritic scars develop
secondary FSGS; poor prognosis
266
what drugs most commonly cause acute drug-induced interstitial nephritis
methicillin, ampicillin, rifampin, diuretics, NSAIDs and alopurinol and cimetidine
267
what are the clincial features of drug induced interstitial nephritis
fever, eosinophilia, rash, and renal abnormalities (hematuria, mild proteinuria, leukocyturia including eosinophils)
268
what is the pathogensis of drug induced nephritis
hypersensitivity; not dose related; IgE mediated or T cell mediated Type IV reaction (delayed hypersensitivity); drugs function as haptens and bind plasma membrane of tubular cells
269
how do you calculate clearance
urine concentration * urine flow rate/ plasma concentration
270
what is the affect of hypoalbuminemia on serum calcium
decreases it without affecting the ionized calcium level; if serum albumin normal, clinical decisions based on ionized calcium levels
271
what is the calculation for corrected calcium
total calcium + .08 (4 - serum albumin)
272
what are the effects of calcitonin
lowers blood calcium by inhibiting calcium absorption in intestines, inhibiting osteoclast activity, and inhibiting renal tubular cell reabsorption of caclium; also inhibits phosphate reabsorption (like PTH)
273
what are the effects of PTH on the kidney
acts in distal nephron to increase calcium reabsorption and inhibits phosphate reabsorption in proximal tubule
274
what stimulates the formation of vitamin D3 (calcitriol) in kidney
PTH
275
where is most of the calcium reabsorbed in the kidney
proximal tubule
276
what are some causes of hypercalcemia
primary hyperparathyroidism, malignancy, thiazide diuretics, milk-alkali syndrome, immobilization syndrome, granulomatous dz, familial hypocalciuric hypercalcemia; vitamin D intoxication
277
how do you manage acute hypercalcemia
- ECF volume replacement with .9% saline
- furosemide
- if does not respond to saline diuresis especially if secondary to malignancy -> *bisphosphonates
- calcitonin
- glucocorticoids
- hemodialysis
278
what is true hpocalcemia and what are some causes
only when ionized calcium reduced; hypoPTH; vit D defi; chronic kidney dz; familial hypocalcemia, pseudohypoparathyroidism; rhabdo; acute pancreaitits; septic shock
279
how do you manage hypocalcemia
- in emergency situation (seizures, tetany, hypotension, arrhythmias): IV calcium
- chronic, mild: oral calcium supplements +/- vit D
- hypoparathyroidism: calcium and vit D supplements
280
what does FGF-23 do to phosphorous
increases renal excretion
281
what effect does vit D3 have on phosphorous
increases intestinal absorption
282
what effect does insulin have on phosphorous
shifts phosphate into cells
283
where is most of the phosporous reabsorbed
proximal convoluted tubule; sodium dependent transporters; regulated by FGF-23 and PTH
284
what are the sx of hyperphosphatemia
signs of hypocalcemia; tissue ischemia or calciphylaxis (vascular calcification or necrosis); renal osteodystrophy
285
how do you manage hyperphosphatemia
acute: saline diuresis
| in ESRD: reduce dietery intake/intestinal absorption via phosphate binders
286
how do you treat renal osteodystrophy
caused by hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia; treat with calcium and vit D supplements
287
what is refeeding hypophosphatemia
cause of death in starving people/anorexics as hexokinase phosphorylates glucose taken into cells
288
how do you manage hypophosphatemia
- moderate: no therapy
- persisitent: oral phosphate
- severe (<1 mg/dL): IV phosphate
- frequently also hypokalemic and hypomagnesemic so must also be corrected
289
where is magnesium found
ICF
290
where is most of the magnesium absorbed
ascending limb driven by NK2Cl transporter
291
what kind of patients do you see hypomagnesemia in
ICU; result of: nutrition, diuretics, albumin, aminoglycosides, PPI
292
what are the sx of hypomagnesemia
weakness, tremor, seizures, vertical and horizontal nystagmus; nonspecific T wave changes; prolonged Qt interval;; premature ventricular contractions; torsade de pointes; v fib; enhanced digitialis toxicity; hypokalemia and hypocalcemia
293
how do you treat hypomagnesemia
oral or IV replacment
294
how do you get hypermagnesemia
ESRD, massive intake (epsom salt), magnesium infusion (given for pre-eclampsia/eclampsia)
295
what are the sx of hypermagnesemia
if less than 3.6 - asymptomatic
if 4.8-7.2: nausea, flushing, HA, lethargy; diminished DTR
if 7.2-12: somnolence, hypocalcemia, absent DTR, hypotension, bradycardia, ECG changes
if > 12: muscle paralysis; flacid quadriplegia, apnea, resp failure, complete heart block and cardiac arrest
296
how do you treat hypermagnesemia
- if normal renal function: stop administration and add loop or thiazide diuretic
- reduced renal function: as above but add saline infusion
- ESRD: dialysis
297
what do a small percentage of patients with analgesic nephropathy develop
urethelial carcinoma of the renal pelvis
298
what are the NSAID-associated renal syndromes
acute kidney injury (ischemia), acute hypersensitivity interstitial nephritis, acute intersitital neprhtisis and minimal change dz, membraneous nephropathy
299
what is acute uric acid nephropathy
caused by precipiation of uric acid crystals in renal tubules leading to obstruction of nephrons and acute renal failure; more likely in ppl with leukemias or lymphomas who are undergoing chemo (drugs kill tumors which produce uric acid)
300
what is chronic urate nephropathy
gouty nephropathy;occurs in patients with hyperuricemia; deposit in distal tubules and collecting ducts; form needle-like crystals; evoke a monocyte response called a tophus
301
which disorders are associated with hypercalcemia
hyperPTH, multiple myeloma, vit D intoxication, met cancer, excess calcium intake
302
what are the causes of papillary necrosis
DM, analgesic nephropathy, sickle cell, obstruction (more in males)
303
when can accumulations of calcium phosphate occur in the kidney
people prepping for colonoscopy
304
how does multiple myeloma cause kidney damage
- bence jones proteinuria and cast nephropathy: Ig light chains directly toxic to epithelial cells; also combine with urinary glycoprotein (tamm-horsfall protein) under acidic conditions to form large tubular casts that obstruct the lumen
- amyloidosis of AL type formed from free light chains (usually lambda)
- light chain deposition disease: light chains (kappa) deposit in GBM and mesangium causing glomerulopathy
- hypercalcemia and hyperuricemia
305
what is suggestive of bence jones proteinuria
light chain proteinuria
306
what is bile cast nephropathy
caused by hepatorenal syndrome; bile casts form in distal nephron; yellowish-green to pink; reversibility depends on severity of liver dz
307
what is the morphology of nephrosclerosis
kidneys are either normal or moderately reduced in size; cortical surface has granularity; loss of mass due to cortical scarring and shrinking; histo: narrowing of lumen caused by hyalinization; fibroelastic hyperplasia; patchy ischemic atrophy (foci of tubular atrophy and interstitial fibrosis and glomerular alterations)
308
what people with nephrosclerosis are at increased risk for developing renal failure
AA, severe blood pressure elevation, ppl with a second underlying dz (esp DM)
309
what is the pathogenesis of malignant nephrosclerosis
vascular injury -> fibrinoid necrosis -> activation of coagulation factors; platelets cause hyperplasia of smooth m of vessels *markedly elevated levels of plasma renin
310
What is the morphology of malignant nephrosclerosis
petechial hemorrhages (flea bitten appearance); onion skinning of interlobular arteries (also called hyperplastic arteriolitis) - correlates with renal failure
311
what are the qualifications for malignant HTN
- systolic >200 diastolic >120
- papilledema
- retinal hemorrhages
- encephalopathy
- CV abnormalities
- renal failure
312
Is fibromuscular dysplasia more common in men or women
women in younger age groups
313
what is the morphology of renal artery stenosis
reduced in size and shows diffuse ischemic atrophy; no arteriosclerosis except maybe in contralateral kidney
314
what are the thrombotic microangiopathies
thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
315
what is the outcome of thrombotic microangiopathies
excessive activation of platelets which deposit in capillaries; consumption of platelets leads to thrombocytopenia and the resulting thrombi create flow ab that shear red cells producing hemolytic anemia
316
what is typical vs atypical HUS
typical: associated with consumption of food contaminated with EHEC
atypical: inherited mutations of complement regulatory proteins; acquired causes of endothelial injury (antiphospholipid ab, complications of pregnancy or OCP, scleroderma, HTN, chemo, radiation)
317
what mutation is TTP associated with
ADAMTS13 (metalloprotease that regulates vWF)
318
what is the initiating event in HUS vs TTP
HUS: endothelial injury
TTP: platelet aggregation
319
who does atypical HUS most often affect
adults; most commonly deficient in factor H (breaks down C3 convertase); Factor I and CD46 also mutations seen;
320
what other conditions does atypical HUS arise with
- antiphospholipid ab syndrome: follows a chronic course
- pregnancy: grave prognosis
- systemic sclerosis or HTN
- chemo
- radiation
321
Is there a better outcome with typical or atypical HUS
typical
322
what are the manifestations of TTP
pentad: fever, neuro sx, microangiopathic hemolytic anemia, thrombocytopenia, renal failure; seen more in women younger than 40 *CNS involvment is dominant feature *treat with plasmapharesis
323
what do cholesterol crystals look like
rhomboid clefts
324
what are the most common abnormalities seen with sickle cell nephropathy
hematuria and diminished concentrating ability (hyposthenuria); the hyperosmolarity dehydrates red cells and increases teh concentration of sickled cells (reason why even those with sickle trait are affected)
325
what can happen as a result of ACE inhibitors
decrease in GFR which will increase serum creatinine; preserves kidney function; <30% increase ok if no hyperkalemia
326
what are sx of hypervolemia
weight gain, edema, bounding pulse
327
what can cause hypovolemia
hypoaldosteronism, adrenal insufficiency, heart failure, cirrhosis, anaphylaxis, sepsis, pregnancy, third spacing, neprhotic syndrome
328
how do you calculae plasma osmolality
2*Na plasma + glucose plasma/18 + BUN plasma /2.8
329
what is normal plasma osmolality
285-295
330
which drugs cause increase vs decrease in ADH
increase: morphine, nicotine, cyclophosphamide
decrease: alcohol, clonidine, haloperidol
331
what are the sx of hyponatremia
SALT LOSS mnemonic
| Stupor/coma, anorexia, lethargy, tendon reflexes decreased; limp mm; orthostatic hypotension, seizures, stomach cramping
332
how do you treat hyponatremia
- severe sx: hypertonic NaCl followed by fluid restirction or vaptan
- Moderate sx: vaptan or hypertonic NaCl followed by fluid restriction
- no or min sx: fluid restriction
333
what happens to the brain with hyponatremia
acute: increased water
chronic: decreased water
334
how do you calculate the amount of 3% NaCl to give to a hyponatremic patient
patient weight in kg * desired correction rate
335
what are the sx of hypernatremia
```
TRIP
Twitching, tremors, hyperreflexia
Restlessness, irritable, confusion
Intense thirst dry mouht, decreases urine output
Pulm and peripheral edema
```
336
how do you tx hypernatremia
- if hypovolemic: isotonic saline
- in other patients, use hypotonic IV solutions
* correct over 48 hrs at .5 mEq/L/hr
337
how do you calculate water deficit
.6 *body weight in kg (1-140/sodium)
338
what is the effect of hypokalemia on the heart
tachycardia
339
what is the effect of hyperkalemia on ECG
high T waves
340
what helps internalize potassium
insulin, beta 2 agonist, aldosterone deficiency, alpha blockers, alkalosis, hypoosomolarity
341
what are the causes of hypokalemia
GRAPHIC IDEA
| GI losses, renal tubular acidosis, aldosterone,paralysis, hypothermia, insulin excess, cushing
342
what are the sx of hypokalemia
skeletal m and smooth m weakness (ileus and constipation); hypotension, arrhythmias; polyuria
343
what are causes of hyperkalemia
Renal dz, excessive intake, drugs, factitious (hemolysis), addisons, tissue release, acidosis, beta antagonists, insulin def
344
what are the sx of hyperkalemia
-bradycardia, peaked T waves, flattened P wave, prolonged P-Q interval, widened QRS, sine wav; weakness
345
what drugs are given for hyperkalemia
renin blockers (NSAIDS, aliskiren), ACEI, aldosterone inhibitors (spironolactone), amiloride, triamterene, trimethroprim
346
how do you tx hyperkalemia
- antagonize cardiac affects - IV calcium
- redistribute K into cells: insulin and glucose OR beta agonist OR bicarb (but generally not recommended)
- facilitate K elimination: K losing diuretic, mineralocorticoid, cation exchange resin, dialysis
347
when does diffuse cortical necrosis usually occur
after obstetric emergency (abruptio placentae), septic shock or extensive surgery
348
what do truly hypoplastic kidneys show
no scars and reduced number of renal lobes and pyramids
349
what are the classifications of renal cysts
- polycystic kidney dz (ar and ad)
- medullary cystic dz (medullary sponge kidney and nephronophthisis)
- multicystic renal dysplasia
- acquired (dialysis) cystic dz
- localized renal cysts
- renal cysts in hereditary malformation
- glomerulocystic dz
- extraparenchymal renal cysts
350
what are the features of AD polycystic kidney dz
large multicystic kidneys, liver cysts, berry aneurysms, mitral valve prolapse; hematuria, flank pain, UTI, renal stones, HTN; renal failure at 40-60 y/o
351
what are the features of AR polycystic kidney dz
enlarged, cystic kidneys at birth; hepatic fibrosis is a complication; death in infancy or childhood
352
what are the features of medullary sponge kidney
medullary cysts on excretory urography; hematuria, UTI, recurrent renal stones; benign dz
353
what are the features of familila juvenile nephronophthisis
AR; corticomedullary cysts; shrunken kidneys; *salt wasting, polyuria, growth retardation, anemia; progressive renalfailure begining in childhood
354
what are the features of adult onset medullary cystic dz
AD; corticomedullary cysts and shrunken kidneys; salt wasting, polyuria; chronic renal failure beginning in adulthood
355
what are the features of multicystic renal dysplasia
not inherited; irregular kidneys with cysts of variable size; renal failure if b/l; curable if unilateral
356
what are teh features of acquired renal cystic dz
cystic degeneration in ESRD; hemorrhage, erythrocytosis, neoplasia are complications; dependence on dialysis
357
what are the features of simple cysts
not inhertied; single or multi cysts in normal sized kidneys; microscopic hematuria; benign
358
what is the pathogenesis of AD polycystic kidney dz
mutations in PKD1 and 2; PKD1 encodes polycystin 1 expressed in tubular epithielial cells *most common mutation; PKD2 (polycystin 2) Ca cation channel; less severe than PKD1 mutations
*thought to be defect in cilia sensing calcium which causes a defect in intracellular calcium
359
in whom is progression of polycystic kidney dz accelerated in
blacks (esp sickle cell), males, and in the presence of HTN
360
what do patients with APKD die of
coronary or HTN heart dz, infection, ruptured berry aneurysm
361
what is the pathogensis of AR polycystic KD
mutations in PKHD1 (expressed in kidney, liver and pancreas) - encodes for fibrocystin - localized to cilium of tubular cells
362
what are the types of medullary cystic dz
medullary sponge kidney, nephronophthisis and adult onset medullary cystic dz
363
what is the cause of renal insufficiency in nephronophthsis and adult onset medullary cystic dz
cortical tubulointerstitial damage
364
what are the variants of nephronophthisis
sporadic, famililal juvenile (most common), and renal-retinal dysplasia
*most common genetic cause of ESRD in children and young adults
365
what do ppl with nephronophthisis present with first
polyuria and polydipsia; tubular acidosis and sodium wasting; some syndromic forms can have extrarenal manifestations (ie: joubert syndrome)
366
what is the pathogensis of juvenile nephronophthisis
mutations in NPHP1-11; (encode nephrocystins)NPH2 encodes inversion (L-R patterning)
367
what mutations are seen in adult onset medullary cystic dz
MCKD1/2
368
what is the morphology of nephronopthsis
kidneys are small, have granular surfaces and cysts in medulla
369
what is the characteristic histo of multicystic renal dysplasia
islands of undifferentiatedd mesenchyme, often with cartilage, and immature colecting ducts
370
what is multicystic renal dysplasia often associated with
ureteropelvic obstruction, ureteral agenesis or atresia, and anomalies of lower urinar ytract
371
what are people with acquired cystic dz at risk for
RCC
372
how can you tell a cyst from a tumor
cysts are smooth, avascular, and give fluid rather than solid signals on US
373
what are the causes of urinary tract obstruction
congenital:posterior urethral valves, uretrhal strictures, meatal stenosis, bladder neck obstuction
stones, BPH, tumors, inflammation, sloughed papillae or blood clots, pregnancy, uterine prolaspe, functional disorders
374
what is hydronephrosis
dilation of renal pelvis and calyces associated with progressive atrophy of the kidney due to obsruction to outflow of urine
375
how do you dx obstructive uropathy
US
376
what occurs after relief of complete urinary tract obstruction
diuresis
377
what are the types of urolithiasis
calcium oxalate, triple stones or struvite stones (magnesium, ammonium, phosphate), uric acid stones, cystine
378
what are causes of calclium stones
hyperoxaluria, hyperuricosuria, hypocitraturia
379
what causes magnesium ammonium phosphate stones
infection by urea splitting bacteria (proteus and staph); form the largest stones *staghorn calculi
380
what are teh features of uric acid stones
ppl with hyperuricemia or acidic urine; radiolucent*
381
what population of people tend to have angiomyolipomas
patients with tuberous sclerosis; can spontaneously hemorrhage
382
what is an oncocytoma
epithelial neoplasm composed of eosinophilic cells that arise from intercalated cells of collecting ducts
383
who is RCC more prominent in
males in 6-7th decade
384
what is the most significant risk factor for RCC
smoking
385
what is hereditary leiomyomatosis and renal cell cancer syndrome
AD; mutation of FH which expresses fumarate hydratase; characterized by cutaneous and uterine leiomyomata and an aggressive type of papillary carcinoma
386
what is hereditary papillary carcinoma
AD; multi b/l tumors with papillary histo; mutations in MET
387
what is birt-hogg-dube syndrome
AD; mutations in BHD which expresses folliculin; skin (fibrofolliculomas, trichodiscomas, and acrochordons), pulmonary (cysts or blebs) and renal tumors
388
what is clear cell carcinoma
most common type; nonpapillary; loss of short arm of chrom 3 (harborbs VHL)
389
what is papillary carcinoma
trisomies 7 and 17 and loss of Y in male patients in the sporadic form; trisomy 7 in famililal form (MET - encodes RTK for hepatocyte growth factor); frequently multifocal in origin
390
what is chromophobe carcinoma
cells with prominent cell membranes and pale eosinophilic cytoplasm with a halo around the nucleus; multi chrom losses and extreme hypodiploidy; grow from intercalated cells of collecting ducts adn have excellent prognosis compared with clear cell and papillary
391
what is Xp11 translocation carcinoma
occurs in young patients and defined by translocations of TFE3 gene located at Xp11.2 with a number of partner genes -> results in overexpression of TFE3; clear cytoplasm with papillary architecture
392
what is collecting duct (bellini duct) carcinoma
arise from collecting duct cells in medular; several chrom losses; malignant cells form glands enmeshed within prominent fibrotic stromg; *medullary carcinom is similar seen in patients with sickle cell trait
393
where do clear cell carcinomas most likely arise from
proximal tubule epithelium - usually as solitary unilateral lesions; yellow color as a result of prominent lipid accumulation
394
where do papillary carcinomas arise from
distal convoluted tubules; multifocal and b/l; hemorrhagic and cystic; composed of cuboidal or columnar cells; form cells common; psammoma bodies can be present
395
what are the clinical features of RCC
costovertebral pain, palpable mass, hematuria; *polycythemia, hypercalcemia, HTN, hepatic dysfuctnion, feminization or masculinization, cushing, eosinophilia, leukemoid rxns, and amyloidosis
396
what are the most common sites of mets of RCC
lungs and bones; LN, liver, adrenal and brain
397
what syndrome is associated with increased risk of urothelial carcinomas of renal pelvis
Lynch and analgesic nephropathy
398
what is teh prognosis for urothelial carcinomas of renal pelvis
not good; infiltrate wall
399
which causes of HTN cause an icrease in volume
low-renin essential HTN; primary hyperaldosteronism
400
what is the most common cause of hydronephrosis in infants and children
ureteropelvic junction obstruction; more common in males (in adults, more common in women)
401
how do you treat HTN in someone with renal dz
ACEI or ARB
402
what does potassium do to BP
lowers it
403
what is captopril
ACEI; side effect: cough and angioedema
- enalapril: prodrug
- benazepril and lisinopril have longer half lives
404
what is losartan
nonpeptide angiotensin II receptor antagonist; side effects: hypoglycemia, hyperkalemia and cough
- valsartan: Not a prodrug
- candesartan: irreversible binding
405
what are the adverse effects of aliskiren
increase in creatine phoshokinase, increased BUN, increased serum Cr; hyerkalemia
406
what medications work well in blacks for HTN
calcium channel blockers and diuretics OR beta blockers, ACE inhibitors and ARBS added to a diuretic
407
who should you not give ACE inhibitors or ARBs to
sexually active girls
408
when should you not give drugs interfering with angiotensin II
renal failure with b/l renal stenosis
409
when is ACEI contraindicated
pregnancy
410
how are bladder cancers defined
invasion of muscularis propria
411
what is a cystocele
when uterine prolapses and brings the bladder with it and the bladder protrudes from the vagina
412
what is the most common cause of hydronephrosis in infants and children
ureteropelvic junction obstruction; more common in males (in adults, more common in women)
413
what is ormond dz
idiopathic sclerosing retroperitoneal fibrosis
414
what is the most common congenital anomaly of the bladder
vesicoureteral reflux
415
when do you see acquired diverticula of teh bladder
prostatic enlargement
416
what can bladder diverticula lead to
infection, calculi, rarely carcinoma which tend to be more advanced in stage
