Exam 3 Flashcards
1
Q
arteries from the start to the end of kidneys (6)
A
- renal arteries
- interlobar arteries
- arcuate arteries at corticomedullary junction
- interlobular arteries
- afferent arterioles branch to supply glomerulus in cortex
- efferent arterioles form peritubular vascualr beds and vasa recta drain glomerulus
2
Q
where is epo made?
A
epithelial cells of peritubular capillaries
3
Q
nephron includes which structures (4)
A
- bowman capsule
- PCT
- loop of henle
- DCT
collecting tubule and duct are not part of nephron
4
Q
what is a renal corpuscle
A
bowman + glomerulus
5
Q
what are the renal medullary structures (3)
A
- lower part of collecting duct
- loops of henle
- vasa recta
6
Q
histological characteristics of proximal convoluted tubules (4)
A
- lots of mitochondria - acidophilic
- apical microvillous brush border
- cuboidal “puzzle piece” epithelium with junctional complexes
- basal striations infoldings - increasing surface area
7
Q
what is the area cribosa?
A
the apex of the renal pyramid where the collecting ducts drain urine through papillary ducts into the minor calyx
8
Q
what lines the visceral and parietal layers of bowman’s capsule
A
visceral = podocytes (with pedicels)
parietal = SS epithelium (continuous with PCT)
9
Q
blood-urine barrier (4)
A
- podocytes of visceral bowman
- diaphragms betwee foot processes of podocytes
- podocyte BM + cap BM = GBM
- fenestrated capillary endothelium
10
Q
low, medium and high MW proteins through blood-urine barrier
A
low can pass directly through
intermediate are blocked by slit diaphragms
high are blocked by endothelial BM
11
Q
what does a mutation in neprhin cause
A
neprhin is a protein that links the podocytes together via the slit diaphragm. mutations in neprhin will cause CONGENITAL NEPHROTIC SYNDROME- massive proteinuria
12
Q
components of the juxtaglomerular apparatus (3) and where they’re located
A
- juxtaglomerular cells (modified SM in wall of afferent arteriole that secrete renin)
- macula densa in the wall of the DCT
- extraglomerular mesangial cells (AKA lacis cells)
13
Q
what do macula densa cells look like and what do they contain
A
columnar, compared to cuboidal DCT cells
chemoreceptors - monitor chemical contents
14
Q
what are JG cells and what do they do
A
intracellular granules of renin
the JG cells are modfified SM cells with mechanoreceptors that release renin when BP falls
15
Q
(extra)glomerular mesangial cells - location and function
A
hold capilaries together in glomerulus
outside pole, make direct contact between JG and MD cells with gap junctions - coordinate activities
16
Q
ureter histological characteristics - muscle (2) and epithelium (1)
A
- upper part by kidney = inner long and outer circular
- lower = inner long, middle circ, outer long
- has stratified transitional epithelium
17
Q
urinary bladder histological characteristics (4)
A
1- poorly defined SM layers
2- luminal transitional epithelium
3- upper part covered by serosa, rest covered by adventitia
4- empty = many layers of round, full = few layers of flat (contain fusiform vesicles)
18
Q
female urethra characteristics (2)
A
3-5cm long
- transitional epithelium near bladder
- stratefied squanous unkeratinized epithelium in vestibule of vagina (maybe some stratefied columnar in the middle)
19
Q
male urethra characteristics (5)
A
10-15 cm long
1. intramural urethra surrounding neck, just below bladder and above prostate, very short
2. prostatic urethra -
transitional near bladder and through prostate gland
3. membranous urehtra with stratefied columnar epitehlium (thinnest part of urethra)
4. spongy/penile urethra with pseudostratefied columnar
5. stratified squamous unkeratinized in fossa navicularis at tip of penis
20
Q
renal stone characteristics (3)
A
- 75% are calcium salts (oxalate and phosphate)
- more in men than women, around 20-30 years
- 10% incidence over lifetime
21
Q
renal stone PAIN characteristics (2)
A
- presents with sudden onset of intense, unilateral, colicky pain with hematuria and vomiting
- painfel with ureteral peristalsis causes movement of stone
22
Q
anatomical landmarks for kidneys
A
- SUPERIOR POLE deep to the 11th (left) and 12th (right) ribs and opposite the T12 (left) to L1 (right) vertebrae
- HILUM is at L1 (left) and L2 (right)
- superior border is diaphragm
- inferior border is quadratus lumborum
23
Q
areas of normal ureteric constriction (3)
A
- renal pelvis - uretopelvic junction
- pelvic brim
- entrance into bladder - uretovesicle junction
24
Q
ureteric calculi pain location
A
pain along T11 to L2 nerve fibers (loin to groin pain)
25
during surgery, where can you damage the ureter
1. crossing the pelvic brim
| 2. passing under the uterine vessels "water under the bridge"
26
muscles in bladder/urethra
1. detrusor smooth muscle in bladder
2. internal urethral spinchter - smooth muscle just under neck of bladder
3. external urethral sphincter - skeletal muscle located in perineum
27
isothenuria
specific gravity of 1.010 approximates plasma (less is dilute, more is concentrated)
28
normal urine pH range
4.5 - 6.0
29
what kinds of proteins does the dipstick pick up
negatively charged proteins, like albumin, but not at low levels
will also not catch immunoglobulins
30
what is the most common protein in normal proteinuria
Tamm-Horsfall protein made in the thick ascending limb of the loop of Henle
up to 150mg is normal
31
what are the kinds of pathologic proteinuria (3)
1- Glomerular proteinuria (albumin)
2- tubular proteinuria (low MW proteins)
3- overflow proteinuria (Ig, light chains)
32
what do you see in urine with nephritic syndrome (3)
1. proteinuria 1-3 grams
2. hematuria (dysmorphic red cells)
3. casts (cellular)
33
what do you see systemically with nephritic syndrome (4)
1. hyptertension
2. renal insufficiency
3. edema
4. decreased urine output (oliguria)
34
what do you see in urine for nephrotic syndrome (2)
1. more than 3.5 grams of protein/day
| 2. lipiduria and oval fat bodies
35
what do you see systemically with nephrotic syndrome (3)
1. edema (anasarca)
2. hypoalbuminemia
3. hyperlipidemia
36
origin of kidneys
intermediate mesoderm - from the urogenital ridge
but the lining is endodermally derived - from cloaca
37
neural control of voiding
1. sympathetic = "storing" T10-L2 relax bladder body and contract bladder base and urethra
2. parasympathetic = "pee" S2-S4 contract bladder and relax urethra
3. somatic - pudendal contracts external sphincter
38
control over detrusor muscle and receptors
sympathetic inhibition - B3 adrenergic receptors
parasympathetic stimulation - muscarinic M2/M3 receptors
39
control over bladder neck and receptors
sympathetic stimulation - alpha1 adrenergic
parasympathetic inhibition - no meds to target these receptors
40
examples of conditions in (+) bladder (4)
cause too much peeing
1. poor bladder wall compliance (amyloid, radation)
2. overactive bladder
3. inflammatory conditions (UTI, IBD)
4. Drugs (caffeine, diuretics etc.)
41
examples of conditions in (-) bladder (3)
cause too little peeing
1. diabetes
2. drugs (anesthesia)
3. bladder diverticulum
42
examples of conditions in (+) outlet (4)
cause too little peeing
1. BPH
2. urethral stricture
3. DSD/pseudo DSD
4. Drugs (adrenergics)
43
examples of conditions in (-) outlet (4)
cause too much peeing
1. prolapse
2. urethral hypermobility
3. surgery - prostatectomy
4. radiation
44
medical treatments for (+) outlet conditions (2)
1. alpha-blocker tamsulosin (symp antagonist)
2. 5 alpha reductase inhibitor finasteride (blocks conversion of testosterone to dihydrotestosterone -
shrinks prostate growth)
45
medical treatments for (+) bladder conditions (3)
1. adrenergic agonist (sympathetic agonist)
2. anticholinergic agonist (parasympathetic antagonist)
3. botox
46
remnants of mesonephros (2)
- male excurrent ducts
| - uroteric bud = outbranch from mesonephric duct (forms ureters and collecting ducts)
47
rudiements of definative kidney
1. uroteric bud (ureter and collecting ducts)
| 2. metanephric blastema (renal corpuscle, PCT, loop fo Henle, DCT)
48
potter syndrome
bilateral renal agenisis causes oligohydramnios - small for date, reduced amnionic fluid.
babies have wrinkled skin, creases below eyes, ear defects, limb defects (limited space)
49
horseshoe kidney
fusion of caudal poles before ascent - gets stuck at level of inferior mesentetric artery (hindgut blood supply)
50
development of urniary bladder
septum in cloaca separates bladder from rectal precursor. urogenital sinus has tip that projects into umbillicus called allantois - most of the time becomes urachus and degenerates, but things can not degenerate properly (have fistula, cyst, or sinus)
51
bladder exstrophy
urachus is open, can get everted bladder and hemi genitalia
52
cystic renal dysplasia cause and clinical presentation
disordered development of kidney maybe due to obstruction of ureter,
clinically similar to agenesis
53
adult polycystic kidney disease cause
- hereditary AD mutation in PKD1 gene on chrom 16 or PKD2 gene on chrom 4 (altered Ca flux or cilia)
54
childhood polycystic kidney disease cause
AR inheritence of mutation of PKHD1 gene on chrom 6p21-23 which encodes fibrocystin, which is essential for collecting duct and biliary differentiation
55
childhood polycystic kidney disease clinical
most commonly presents with neonatal renal failure. may be similar to renal agnesis but with enlarged and palpable kidneys
sometimes hepatic fibrosis with minimal kidney disease
56
childhood polycystic kidney disease gross and histo presentation
enlarged, only involves collecting ducts - outer surface is smooth. only involves medulla.
57
adult polycystic kidney disease gross and histo presentation
grossly, cysts everywhere
histo, fibrosis, flattened tubules, inflammatory infiltrate, hypertensive hyaline tubules, sometimes hemosiderin laden macrophages
58
adult polycystic kidney disease clinical presentation
clinical presentation in older patients - hematuria, hypertension, ab pain, renal infection, berry aneurysms, mitral valve prolapse, hepatic cysts, colonic diverticula
patients can survive for a while - low incidence high prevalence
59
cystic renal dysplasia gross and histo findings
grossly large and multicystic
micro have primative glomerular structures and cartilage
60
medullary sponge kidney cause and clinical
unknown pathogenesis, causes multiple cystic dilation of collecting ducts
asymtomatic usually, discovered in adults incidentally or due to complications such as infection hematuria and kidney stones
61
variants of nephronophthisis
1. sporadic, non-familial
2. familial juvenile (most common) adult medullary cystic disease
3. renal-retinal dysplasia
62
genetic causes of nephronophthisis
most common - familial juvenile - AR mutation of NPHP1-11, JBTS2, JBTS3, JBTS9, JBTS11
or AD mutation of MCKD1 and MCKD2 in adult medullary cystic disease
63
nephronophthisis gross and histo presentation
kidneys normal or small in size
cysts along corticomedullary junction
involve distal tubules with tubular basement membrane with fibrosis, inflammation and edema
64
simple cortical cyst cause and findings
incidental findings, asymptomatic, 1-5cm cysts with flattened or cuboidal epithelium
65
dialysis associated cystic disease findings
multiple corticomedullary cysts, fibrosis, oxylate crystals, increased risk for renal cell carcinoma
66
tubular reabsorption
transfer of substances OUT of tubular lumen INTO peritubular capillaries (for goodies like AAs and glucose)
67
tubular secretion
transfer of substances FROM peritubular capillaries INTO tubular lumen (for metabolic products)
68
excretion rate equation
excretion rate = filtration rate - reabsorption rate + secretion rate
ER = FR - RR + SR
69
ohm's law
Q = deltaP / R
70
driving pressure in the kidney (delta P) and glomerulus
kidney deltaP = renal artery P - renal vein P
glomerulus deltaP = afferentP - efferentP
71
what area of kidney is the most perfused
the cortex ~95% of blood flow
72
what cells regulate the surface area of the glomerulus
intraglomerular mesangial cells
73
what is the interstitium around the vasa recta like
hyperosmolar (need gradient for water reabsorption)
in the peritubular capillaries its about equal to plasma
74
cortical nephrons - characteristics and purpose (4)
- 80-85% of tubules
- short LoHs with little/no thin ascending
- purpose is secretion and reabsorption
- no vasa recta
75
juxtamedullary nephrons - characteristics and purpose (4)
- 15-20% of tubules
- very long LoHs
- have vasa recta
- purpose is to generate very concentrated urine - generates osmotic gradient
76
which passes through the glomerulus easier, positively charged, negatively charged, or neutral particles?
best is positive, then neutral, then negative
| - larger molecuels that are postiively charged go through much much easier than negative (proteins, like albumin or Ig)
77
what causes this difference in charge preference in glomerular filtration?
fenestrae, BM and slits have negative charge
78
what physiological changes happen in diabetic nephropathy
thickekning of BM and mesangial matrix, reducing ability of molecules to get into filtrate, reducing GFR
79
starling equation/ glomerular filtration rate equation
Jv = Lp x A ((net hydrostatic out) - (net oncotic in))
```
Jv = fluid moving across capillary
Lp = permeability
A = surface area
```
rest is net filtration force AKA ultra filtration pressure = what kidney regulates
80
what happens to pressure over the length of the glomerulus
net hydrostatic pressure stays the same
increasing concentration of protein within capillary, so cap oncotic pressure increases (but this value stays below the net hydrostatic pressure to keep flow unidirectional)
81
what is the main starling force that determines ultrafiltration?
Pgc = hydrostatic pressure in the glomerular capillary
82
renal plasma flow equation
= renal blood flow x (1-hematocrit)
= 1200 mL x 50%
= 600mL/min
83
how much of the plasma that gets into the kidney gets filtered through the glomerulus
20%
84
so what's an estimate of GFR
0.2 x renal plasma flow
= 0.2 x 600
= 120mL/min
normal is 120-140
85
how do mesangial cells affect GFR
can affect surface area A - if they contract, they reduce surface area and decrease GFR
86
how do you change hydrostatic glomerular cap pressure?
target:
1. renal arterial BP
2. afferent arteriolar resistance
3. efferent arteriolar resistance
87
what is glomerular pressure in relation to systemic pressure under normal conditions
half. because you have two arterioles (afferent and efferent) at the same resistance
88
what happens to GFR if you constrict afferent arteriole
decrease Pgc, decrease GFR
89
how can you constrict afferent arterioles
with adrenergic agonists - increased sympathetic activity and increased circulating catecholamiines
90
what happens to GFR if you constrict efferent arterioles
increase upstream Pgc and increase GFR
91
how can you constrict efferent arterioles
low levels of Ang2 (because at high levels, afferent would also be constricted)
92
when do you have myogenic response
during an acute change in BP - responds in 1-2 seconds
93
what is the myogenic response
High BP:
afferent senses the stretch due to increased systemic BP and clamps down in response
Low BP:
afferent will dilate
94
how does the juxtaglomerular apparatus regulate GFR in response to high BP (2)
juxtaglomerular apparatus includes macula densa and juxtaglomerular ccells
1. macula densa are specialized epithelial cells that senses sodium chloride and releases ATP -> adenosine -> constriction of afferent, reducing Pgc
2. juxtaglomerular cells are specialized SM that have renin granules. release is inhibited by the adenosine released by macula densa during HTN, leading to decreased ang2, which causes dilation of efferent arterioles, reducing Pgc
95
when do you have how does the juxtaglomerular apparatus regulation of GFR
during long term changes in BP
96
how does the juxtaglomerular apparatus regulate GFR in response to low BP (2)
1. decreased NaCl causes macula densa to release NO and prostaglandins to dilate the afferent arterioles to increase Pgc
2. prostaglandins cause juxtaglomerular cells to release renin granules which results in high Ang 2, which constricts efferent arterioles to increase Pgc
97
what mechanisms does the kidney use to regulate GFR and why does it do it
1. myogenic (afferent constriction/dilation short term)
2. juxtaglomerular apparatus
to maintain normal GFR for kidney function
98
what mechanisms does the body (Extra-renal) use to regulate GFR and what does it do it
1. neural
2. hormonal
to maintain normal volume and perfusion throughout the body
99
what are the neuronal extra-renal responses on GFR to big drop in BP (i.e. in hemorrhage) (2)
1. baroreceptors increase symp activity which stimulate B1 receptors on juxtaglomerular cells which increase renin release (at high Ang2, afferent is constricted too) and also
2. stimulation of alpha 1 receptors in afferent arteriole to promote constriction
causes reduced kidney perfusion
100
what is the hormonal extra-renal response to GFR in response to high BP (6)
1. stretch in ventricle causes release of brain naturetic peptide, stretch in atria causes release of atrial naturetic peptide
natiuretic peptides dilate afferent arteriole cells
2. ANP and BNP also relax mesangial cells, increasing surface area, causing increased GFR, resulting in greater excretion of sodium and water
3. ANP and BNP constrict efferent arterioles
4. increased blood flow in vasa recta - to was away osmotic gradient - allowing for dilute urine and decreased fluid retention
5. decreased sodium reabsorption in DCT and cortical collecting ducts via phosphorylation of sodium channels
6. inhibit renin and aldosterone secretion
101
theoretically, how do you get 100% clearance
free filtration (20%) + 100% secretion (rest of the 80%)
clearance/excretion is MORE than GFR - clearance is equal to RPF (renal plasma flow) like with PAH
102
theoretically how do you get 0% clearance
filtration (20%) - reabsorption (same 20%)
clearance/excretion is LESS than GFR - basically 0 clearance, like with GLUCOSE
103
when does GFR = clearance/excretion?
when there is just filtration
like with inulin or ~creatinine
104
clearance equation
Cx = mass in the urine / plasma concentration
Cx = Ux x V / Px
```
Ux = conc in the urine
V = urine flow rate
Px = conc in plasma
```
105
excretion equation
= V x Ux
| = urine flow rate x urine conc
106
how to measure GFR by measuring substances in urine
inulin = substance that is freely filtered and NOT reabsorbed, secreted or metabolized = JUST filtered
creatinine from muscle, freely filtered and slightly secreted but also overestimated, so equals out. so clearance = GFR
= mass of creatinine/ plasma creatinine
= (Ucreat x flow rate)/ Pcreat
107
what's the theoretical relationship between GFR and plasma creatinine
inverse --> theoretically if GFR falls to 25% of normal, Pcr should increase 4x
108
whats the minimum normal value for GFR
60
| that's 50% of normal (120)
109
filtered load equation
for a free filtered substance
| FL = GFR x Px
110
fractional excretion equation
= amount excreted/amount filtered
= mass in urine/ filtered load
= Ux x V/Px x GFR
= 100 x Una/Sna x Scr/Ucr
111
primary causes of nephrotic syndrome (3)
1. minimal change glomerulopathy
2. membranous glomerulopathy
3. focal segmental glomerulosclerosis
112
primary causes of nephritic syndrome (3)
1. proliferative glomerulonephritis
2. acute diffuse proliferative glomerulonephritis
3. crescentic glomerulonephritis (worst, can become rapidly progressive glomerulonephritis)
113
what's the most common nephrotic syndrome in kids
minimal change disease (80%)
114
what would you do for someone with minimal change disease
predisone - have to give steroids to immunosuppress
115
what do you see on histo (2) and TEM (1) for minimal change disease (3)
almost normal at low power:
1- no increased cellularity
2- no interstitial inflammation
3- on TEM you see effacement of podocytes - fusion, continuous lining
116
african americans are more likely to have what kind of nephrotic syndrome
FSGS - focal segmental glomerulosclerosis because of APO mutation that protects against african sleeping sickness - trypanosomiasis
117
what histo changes do you see in FSGS (3)
1- some (not all) glomerular collapse, shrinking in bowmans space (higher power see only PART of the glomeruli are affected) i.e. focal segmental
2- dilation of tubules with casts
3- sclerosis of capillary in some parts and adhesion to bowman's capsule in those parts
118
what do you see on IF in FSGS
IF is non-specific positive only in areas of sclerosis - no immune complex deposition
119
which is more favorable, minimal change, membranous nephropathy or FSGS
minimal is best -
responds better to steroids and tend not to progress.
membranous is in the middle - 1/3 progress, 1/3 remission, 1/3 stable
FSGS the worst - progression is more likely
120
what are other associated conditions with FSGS (4)
1. HIV (sit and replicate inside podocytes)
2. sickle cell (hyperfiltration and secondary form of FSGS)
3. morbid obesity (hyperfiltration and sclerosis of glomer cap bed)
4. pamidronate (bisphosphonate for osteoperosis)
121
what do you see in histology for membranous nephropathy (4)
1. diffuse involvement
2. cap walls are thickened - BM thick
3. no increase in cellularity
4. no inflammation
122
what do you see on GMS stain for membranous nephropathy
diffuse thickening of BM with "spikes" of GMS pos BM surrounding pale sites of epimembranous subethithelial deposit (indicating immune complex deposition)
123
what do you see on IF for membranous nephropathy
diffuse granular deposit along whole BM
124
what do you see on histology for diabetic nephropathy (5)
1. nodular slcerosis in mesangium and afferent and efferent
2. arterial hyalinzation
3. lymphocytic infiltrate
4. diffuse thickening of BM without immune deposition
5. iscemic necrosis of papillae
125
do you give predinsone for diabetic nephropathy?
no because it raises blood sugar
126
what do you see in histology (2) and EM (1) for post-infectious glomerulonephritis
1. diffuse global increase in cellularity within glomeruli (polys)
2. proliferation of cell types (epithelial and mesangial)
3. TEM humps on subepithelial
127
what do you see on IF for post-infectious glomeruloneprhtis
global chunky "starry sky" appearance caused by complex deposits at the subeptithelial aspect of BM
128
what is C3 level for post infectious glomerulonephritis
low - because of immune complex
129
what do you see in histo for lupus nephritis (5) and EM (1)
1. diffuse involvement of glomeruli
2. some have focal sclerosis, some are totally scarred over
3. thickened capillary walls
4. slight increase in mesangial cells, no infiltrate
5. large subendothelial deposits on GMS and PAS- immune complex deposition
6. effacement of podocytes on EM
130
what do you see on IF for lupus nephritis
"full house" staining (IgG, IgM, IgA, C3, C1q) in capillary loops and mesangium
131
what do you see on histology for goodpasture's symdrome (3)
1. diffuse glomerular involvement, some completely sclerosed
2. increased cellularity beneath bowman's capsule (macrophages and epithelial cells) in crescent shape with fibrinoid necrosis
3. RBCs in urinary space and tubules
132
what do you see on IF for goodpasture's syndrome
linear staining of BM positive for IgG and C3 - not granular (no immune complex depositions)
133
what are clinical clues for goodpasture's syndrome
both renal and pulm involvement with rapidly progressing glomerulonephritis (can have crescents)
134
what serologic test would be helpful in diagnosis for goodpasture
Anti-GBM titer
135
what do you see on histology for microscopic polyangiitis (2)
1. vascular space with destruction of wall by inflammatory cells - vasculitis - seen in both renal and skin biopsy
2. focal segmenting glomerulonephritis with crescents
136
what do you see on renal IF and skin for microscopic polyangiitis
nothing in renal, skin has C3, IgM and fibrin
137
clinical clue with microscopic polyangiitis
purpura - skin involvement
138
what serology test would you ask for if you suspect microscopic polyangiitis
antineutrophil cytoplasmic antibody (ANCA) titer
139
what do you give for goodpastures and ANCA vasculitis
combination of steroids and cyclophospholides or ritoximab or plasmophoresis
140
paracellular pathway
movement across tubular epithelium across TIGHT JUNCTIONS depending on electrochemical gradient and permeability properties of the TJ
141
transcellular route
includes trans-apical, trans-basal and trans-lateral
| depending on electrochemical driving force and active energy transport with channels and transporters
142
difference between simple and facilitated diffusion
simple is through the membrane itself, facilitated is using carriers BOTH are WITH the electrochemical gradient
143
difference between primary and secondary active transport
BOTH require energy and are AGAINST the electrochemical gradient.
primary uses an ATPase
secondary uses the downhill movement of one substance to provide energy required to move the other substance against the gradient (cotransport/symport = 2 molecules go in the same direction, countertransport/antiport = opposite)
144
endocytosis vs transcytosis
endo is outside into the cell, trans is outside all the way through to the other side
145
how does sodium get from tubular lumen to capillary
there's a high sodium concentration in the tubular lumen and lower concentration in the tubular epithelial cell, so the sodium passively diffuses into the cell.
then, the sodium gets pumped into the interstitium via a sodium potassium ATPase that pumps 3 molecultes of sodium out for ever 2 molecules of potassium in.
then the sodium will get into the BV via oncotic pressure, which also pulls other solutes via solvent drag (2/3rd get reabsorbed this way in proximal tubule)
146
what is solvent drag
movement of solutes with water that's moved by osmosis
147
how do glucose and amino acides get from tubular lumen into BV
transcellular via sodium/glucose cotransport/symport (sodium linked glucose tranpsorters - or AA transporters) in apical membrane, and then gets into interstitium passively along gradient
148
what happens if you have too high a concentration in the tubular lumen
the transporters are saturable, so there's a limit and you'll get glucose and AAs in urine
glucoseria via diabetes mellitus, for example
149
what is type A renal glucosuria?
there is defect that causes a reduced affinity of SGLT2 (the sodium/glucose transporter) so you get less reabsorption of glucose and you get benign mild-severe glucoseria
150
what happens to organic anions and cations? what is used?
```
want them to be secreted.
secretion happens via 3 protein types in proximal tubule:
1. organic cation transporters
2. organic anion transporters
3. multidrug resistance proteins (p-
glycoprotein --> cyp3a4 associated)
```
151
how do we get rid of cations?
OCT sits on basolateral surface, which gets cation into cell, export of cation into tubular lumen is driven by exchange of protons with cation at apical surface via acid gradient (which is maintained by sodium/proton exchanger)
THUS this is all maintained by SODIUM/POTASSIUM ATPase so that intracellular sodium remains low, so that protons can pump out for exchange of sodium in with its gradient, creating acid gradient to bring proton back in in exchange for cation out
152
how do we get rid of anions?
have OAT on basolateral surface. OAT brings anion into cell via the establishment of a gradient with sodium and alpha KG transporters. MDR (p-glycoprotein) allows anion to go into tubular lumen via ATPase. this is also driven by SODIUM/POTASSIUM ATPase, but also MDR ATPase
153
is creatinine an anion or a cation
cation
154
what are anions are secreted in proximal tubule (7)
endogenous:
1- oxylate
2- urate
exogenous:
3,4,5,6- FACE diuretics (furosemide, acetazolamide, chlorothiazide, ethacrynate)
7- PAH
155
PAH characteristics
freely filtered AND avidly secreted - can get complete clearance of this molecule --> this can tell us what RENAL PLASMA FLOW is
156
how do you calculate for renal blood flow from renal plasma flow
RBF = RPF / (1-Hct)
since plasma is only a part of total blood flow
157
what happens to clearance of glucose and PAH as you keep increasing plasma concentration
eventually, they both reach around GFR - PAH can't be fully secreted and glucose can't be fully reabsorbed
158
what happens to clearance of glucose and PAH as you keep increasing the flow through the tubular lumen
same thing with increased concentration - eventually both get clearance that's equal to GFR
159
how do smaller peptides get into tubular epithelium
peptidases on the tubular surface break them down and abosrb AAs via AA/Na+ cotransporters, then get dumped into interstitial space and back into circulation
160
how do larger peptides get into tubular epithelium
two options:
1. intact - can be trancytosed
2. if not recognized as intact, can get endocytosed, degraded and get then get into interstitial space
161
what happens to ions in thin descending loop of Henle
nothing, thin descending loop is impermeable to ions. only thing that's permeable is water
162
what happens to sodium ions in the thick ascending loop of Henle
about 25% of sodium is reabsorbed via the sodium/potassium/2 chloride cotransporter
furosemide inhibits this cotransporter - strong effect
163
what happens to sodium ions in distal convoluded tubule
4% of sodium is reabsorbed via sodium/chloride cotransporter
164
what happens to sodium ions in collecting duct
3% of sodium reabsorbed via luminal membrane aldosterone-sensitive sodium channel (ENaC)
165
what are the main sodium transporters in proximal tubular epithelium (4)
basolaterally =
1- sodium/potassium ATPase
apically =
2- cotransproters (AA, glucose, phosphate)
3- countertransport (protons)
4-some paracellularly with chloride and water in solvent drag
166
what are the main sodium transporters in the thick ascending loop of Henle
apically =
1. sodium/potassium/2 choride contransporter (inhibited by LOOP DIURETICS - furosemide) which creates backleak of potssium, driving paracellular flow into interstitium
2. paracellular: flow of cations (Na+ K+ Ca++) out of tubular lumen into interstitium because of gradient set up by potassium leak channels (more positive in lumen)
167
is thick ascending limb permeable or impermeable to water?
impermeable
168
is thin descending loop of Henle permeable or impermeable to water?
permeable ONLY to water, nothing else
169
is early distal convoluted tubule permeable or impermeable to water?
impermeable
170
how does sodium get transported in the early distal convoluted tubule
via sodium/chloride cotransporter (inhibited by THIAZIDE diuretics)
171
is the late distal convoluted tubule/ collecting duct permeable or impermeable to water?
it's variable - under control of ADH
172
how does sodium get transported in the late distal convoluted tubule/ collecting duct?
1. luminal epithelial sodium ENaC channels
2. basolateral sodium potassium ATPase
BOTH are stimulated by aldosterone (increased expression and activity)
173
what does increased sodium fractional excretion value tell you
that there's an intrinsic renal problem - less sodium reabsorption, more sodium excretion
174
what happens with chloride reabsorption in proximal convoluted tubule (what percentage and how)
60% reabosrbed paracellulary predominately via solvent drag
175
what happens with chloride reabsorption in thick ascending limb (what percentage and how)
30% reabsorbed via sodium/potassium/2 chloride cotransporter
176
what happens with chloride reabsorption in early distal convoluted tubule (what percentage and how)
7% via transcellular Na+/Cl- cotransport
177
what happens with chloride reabsorption in late distal convoluted tubule/collecting duct (what percentage and how)
3% via transcellular countertransport with bicarb with beta-intercalated cells
178
fanconi's syndrome
generalized dysfunction in PCT cotransporters
this impairs kidney function and production of vitamin D - get bone disease
179
hyperkalemia causes what to resting membrane potential
depolarization
180
hypokalemia causes what to resting membrane potential
hyperpolarization
181
relationship between potassium and acid-base balance
too much acid in plasma triggers potassium proton antiporter - get potassium leaving cell, have risk for becoming hyperkalemic acidosis
too little acid causes increase movement of potassium into cell and you get hypokalemic alkalosis (also often see hypochlorinic)
182
relationship between insulin and potassium
insulin and epinephrine stimulate sodium/potassium ATPase, so you can help patient with hyperkalemia by administering insulin
183
how much and how is potassium transported in PCT
67% via paracellular solvent drag
184
how much and how is potassium transported in thick ascending limb
20% via na+/K+/ 2Cl-
| and ROMK2 backleak channel
185
how much and how is potassium transported in distal convoluted tubule and collecting duct?
variable (10-50%) depending on what your potassium load is.
if you're hyperkalemic, secretion will occur via PRINCIPAL cells in an aldosterone-sensitive fasion, also affected by luminal sodium levels (distal sodium delivery = potassium wasting)
if you're hypokalemic, reabsorption will happen via apical H+/K+ ATPase in alpha-intercalated cells (only activated in low intracellular potassium)
186
Bartter and Bartter-like Syndrome
- defects in ROMK2 and NA+/K+/2Cl- channels lead to electrolyte disturbances, bone disorders, growth and cognitive disorders
187
inorganic phosphate and Ca2+ together are soluble or insoluble?
insoluble - they make bone
188
phosphate transport in proximal convoluted tubule - how much and how?
variable - 30-80% via sodium/phosphate cotransporters - can regulated by parathyroid hormone (in response to low calcium, PTH decreases phosphate levels to prevent formation of crystals in blood)
189
phosphate transport in proximal straight tubule - how much and how?
varaible, ~ 5% paracellular solvent drag AND transporters that can be expressed when you need to recover phosphate
190
phosphate transport in distal convoluted tubule - how much and how?
variable 10-15% paracellular solvent drag AND transporters that can be expressed when you need to recover phosphate
191
how and how much calcium is transported in PCT?
70% via paracellular solvent drag
192
how and how much calcium is transported in the thick ascending limb?
20% driven by potassium positive charge and paracellular flow
193
how and how much calcium is transported in the distal convoluted tubule
9% via luminal calcium channels under the control of PTH - upregulated by PTH
194
chronic kidney disease and vitamin d
kidney is where vitamin D is activated, so you get loss of bone and low plasma calcium and high PTH -- severe bone defects
195
where do you get most of your magnesium reabsorption
in the thick ascending limb (50-60%) paracellularly due to positive lumen charge with potassium backflow
reaborption in low in PCT (20-30%) because it doesn't work as well with solvent drag
196
what happens to urea in PCT
50% via passive reabsorption paracellularly through tight juctions (NO TRANSPORTERS IN PCT)
197
what happens to urea in the loop of Henle
that same 50% is secreted via urea transporters
198
what happens to urea in collecting duct
50% reabsorbed again via urea transporters
199
in a general sense, are the ascending tubules permeable or impermeable to water?
impermeable. the descending tubules (PCT, DLH, CD) are impermeable
200
what regulates the acquaporin vessicle docking?
ADH - ADH stimulates apical membrane channels to increase water reabsorption in the COLLECTING DUCT
in nephrogenic diabetes, there's an ADH receptor defect, so you don't get water reabsorbtion
201
what is lithium associated nephropathy
lithium looks like sodium, accumlates in collecting duct via the ENaC channels which in turn downregulates ADH regulated aquaporins
202
iondine-rich contrast induced neprhopathy
contrast is cytotoxic to PCT
203
calcineurin inhibitor nephrotoxicity
get tubular resistance to aldosterone and resulting hyperkalemia
204
heavy metal (Pb, Cd) nephropathy
PCT dysfunction leading to hyperuricemia, gout and HTN
205
aldosterone has an effect on what channels? (3)
K channels,
ENaC
Na+/K+ ATPase
206
what's the gradient from cortical side to papillary side
300 mOsm/L
| 1200 mOsm/L
207
in "Active transport" region of medulla (upper portion with thick ascending) which area has highest and lowest sodium concentration
interstitium is higher than both thick descending and thin ascending
208
in "passive transport" region of medulla (lower portion with thin ascending) which area has highest and lowest sodium concentration
thin ascending > interstitium > thin descending
209
what is the net flow in the descending vasa recta
sodium in
210
what is the net flow in the ascending vasa recta
water in
211
what is the [NaCl] difference at any level through the vasa recta and interstitum
ascending > interstitium > descending
212
What transporters does ADH control (3)
urea transporters
Na/K/2Cl
aquaporins
213
regulators of ADH release (3)
1. plasma osmolality (major) - increased plasma osmolality increased ADH release (very sensitive, causes small changes)
2. blood volume, sensed by stretch receptors, less sensitive but more potent
3. systemic arterial BP - sensed by stretch receptors, less sensitive but more potent
214
free water clearance
positive if urine has lower concentration than plasma (low ADH)
negative if urine has higher concentration than plasma (high ADH)
215
central diabetes insipidus, cause and treatment
caused by too little ADH release from posterior pituitary (caused by brain trauma, infection or neoplasms), treated by exogenous ADH
216
nephrogenic diabete insipidus cause and treatment
caused by lack of response of kidney collecting duct cells to ADH (may be caused by lithium) cannot be treated by exogenous ADH
217
Syndrome of inappropriate ADH secretion (SIADH) cause and treatment
elevated plasma ADH relative to plasma osmolarity and have very concentrated water(can accumulate excess water if not restrained) - caused by brain infections, neoplasms, anti-tumor drugs and lung cancer
218
what does the active form of vitamin D do systemically (3)
gets activated by PTH in the proximal tubules in response to low plasma calcium levels
1. increases gut Calcium uptake
2. decreases calcium loss in kidney
3. decreased bone reabsorption
219
chronic low vitamin D would cause what effect on phosphate levels
because your vitamin D is low, your parathyroid hormone is high which leads to increased plasma levels of calcium and phosphate. in order to avoid crystals being formed in the blood, phosphate reabsorption is decreased
220
which diuretics are potassium wasting? (3)
those that work early in the nephron delivering high sodium load to distal nephron
Loop diuretics AKA Na/K/2Cl blockers (TALH):
1. furosemide
2. ethacrynic acid
Thiazide diuretics AKA Na/Cl blockers (DCT):
1. hydrochlorothiazide
221
which diuretics are potassium sparing? (3)
those that act at collecting duct (late)
inhibitors of ENaC (CD):
1. amiloride
aldosterone antagonists (CD):
2. spironolactone
3. eplerenone
222
what are examples of diseases that lead to "edematous states" (4)
1. CHF
2. pulm edema
3. nephrotic syndrome
4. hepatic cirrhosis
223
what are the reflex compensatory mechanisms when first starting a diuretic
- sensed as low blood pressure,
1. actvates symp activity
2. RAAS pathway
3. increased ADH
4. decreased ANP
results in diuretic "braking" - establishing a new set point
224
what's an example of an osmotic diuretic? where does it work
mannitol - througout but starts in PCT
225
what's an example of a carbonic anhydrase inhibitor and where does it work?
in PCT - acetazolamide
226
what's an example of ADH antagonist and where does it work
tolvaptan - CD
227
What does carbonic anhydrase do? what happens if you inhibit it (2)
converts bicarb and CO2 into water
1. less resorbtion of bicarb anion, which leads to less sodium leaving because you are pumping less protons into the lumen via Na/H antiporter. this INCREASED LUMINAL SODIUM is sensed by the MACULA DENSA which releases ATP, increasing adensoine, leading to afferent arteriolar contraction, decreased renin, increased efferent relaxation (reduces GFR because it senses high Na as high blood pressure) -- DIURETIC BRAKING
2. also, at the collecting duct, you have high bicarb, increasing negative charge of lumen, causing K+ loss and Cl retention (HYPOKALEMIC, HYPERCHLORINIC)
228
uses for acetazolamide (3)
1. metabolic alkalosis (to correct the alkalosis caused by other loops/thiazides, decreasing bicarb in plasma)
2. decrease intraocular pressure topically
3. acute mountain sickness (in anticipation of resp alkalosis)
229
adverse effects of acetazolamide (2)
1. renal stones (calcium salts are less soluble at alkaline urine pH)
2. cross-hypersensitivity with other sulfonamides
230
what are loop diuretics the best for?
reducing blood volume
231
loop diuretic effect on ions
inhibiting the resporption of potassium into the cell (inhibits the Na/K/Cl transporter). thus you have less backleak back into the lumen. this decreases the reabsorption of calcium and magnesium which used this backleak channel for a charge gradient for paracellular transport. thus, causes HYPOCALCEMIA and HYPOMAGNESEMIA
232
what are the overall effects of loop diuretics (3)
1. get increased luminal Na, Cl and K due to inhibition of the rock channel (also leads to hypocalcemia and hypomagnesemia because no more potassium back leak)
2. the macula densa uses the Na/K/2Cl to sense sodium and chloride, so loop diuretics inhibit their ability to sense the increases in sodium and chloride in the DCT. thinks you're not filtering enough, so works to INCREASE GFR through prostaglandins and NO, increasing renin release and increased aldosterone -- diuretic braking
3. also get potassium WASTING and ALKALOSIS downstream in the collecting duct because of negative charge from chloride.
233
what happens when you first take furosemide?
in large doses, abolishes osmotic gradient, and thus you get very dilute urine - high diuresis
but once compesnatory mechanisms kick in (renin, increased RBF) you reesablish baseline and improve osmotic gradient
234
what is first line approach for patient with hypertension and congestive heart failure
furosemide
235
adverse effects of loop diuretics (5)
1. low ion levels (K, H, Mg, Cl etc.)
2. cardiac arrhythmias (toursades)
3. hypotension due to hypovolemia (esp in elderly)
4. ototoxicity
5. hyperuricemia (gout)
236
what do thiazide diuretics cause? (3)
1. thiazides inhibit the Na/Cl symporter in the DCT - resulting in higher Na and Cl levels in the urine
2. this sodium gradient drives a basolateral sodium calcium exchanger, causing more resorbtion of calcium (HYPERCALCEMIA)
3. increased sodium delivery to collecting duct, leading to potassium wasting and proton secretion (HYPOKALEMIA, ALKALOSIS)
237
what do you use in conjunction with thiazide diuretics?
ACE inhibitors to combat hypokalemia
238
uses for loop diuretics (2)
1. edema
| 2. hypertension (with heart failure esp)
239
uses for thiazides (4)
1. hypertension - first choice for simple essential HTN
2. CHF (reduces morbitidy)
3. Hypercalcinuria - prevent renal stones
4. nephrogenic diabetes insipidus
240
adverse effects for thiazides (4)
1. electrolyte imbalance (HYPOKALEMIA, HYPERCALCEMIA, HYPERURICEMIA)
2. hypotension
3. hyperglycemia in patients with diabetes
4. hyperlipidemia
241
ENaC blocker effects (2)
1. amiloride inhibits sodium ENaC channels, indepedent of aldosterone
2. get decreased excretion of K and H (HYPERKALEMIA, ACIDOSIS)
242
uses for ENaC blockers (1)
1. in conjunction with thiazides or loops to spare potassium
243
adverse effects for ENaC blockers
1. hyperkalemia (esp in renal disease)
244
does amiloride decrease morbidity?
yes, for elderly patients in conjunction with HCTX
245
effect of aldosterone inhibitors (3)
most effective when aldosterone is high
1. inhibits potassium channel (less potassium secretion - HYPERKALEMIA)
2. inhibits ENac expression (less sodium reabsorption)
3. inhibits Na/K ATPase
246
adverse effects of aldosterone antagonists
1. hyperkalemia
| 2. gynecomastia esp spironolactone (and menstural irregularities in women)
247
do aldosterone antagonists decrease mortality?
yes, in heart failure patients when given in combo with loop or thiazide
248
osmotic diuretic effects (3)
(mannitol)
1. freely filtered, increasing osmomtic suction to keep water in the lumen - remain in the tubule the whole way. thus, they work at sites where water is permeable (tDLH for example)
2. increase plasma osmolality, increasing RBF, due to increased vascular volume
3. increased magnesium excretion for unkonwn reason
249
therapeutic use for mannitol (1)
reduce intracranial or intraoccular pressure before and after sx
250
adverse effects for mannitol (1)
hyperkalemia, shrinks cells, increasing intracellular [K], causing passive diffusion out
251
vasopression antagonists effect (1)
(tolvaptan)
| block ADH signalling, block production and docking of aquaporins in CD
252
use for vasopressin antagonists (1)
SIADH
253
can you add a loop to a thiazide?
yes, you get synergism for sodium excretion, however, be careful because you can get severe postural hypotension
254
what is effective vascular volume?
part of the ECF that is in the vascular space AND effectively perfusing the tissues
determined by ECF fluid volume, CO and vascular tone. related to BP
255
ECF volume is related to sodium or water?
sodium
256
TBF Osmolality is related to sodium or water?
water
257
where are the osmoreceptors
hypothalmus
258
what are the clinical signs of volume depletion (5)
1. orthostatic decrease in PB and increase in pulse rate
2. decreased pulse volume
3. loss of axillary sweating
4. decreased skin turgor
5. dry mucous membranes
259
what are clinical signs of volume expansion (6)
1. edema
2. pulm crackles
3. ascites
4. JVP distension
5. hepatojugular reflex
6. hypertension
260
volume depleted state causes what physiological effects? (3)
1. increased symp activity (leads to Na reabsorption in kidneys)
2. RAAS (leads to Na reabsorption via Ang2 and aldosterone)
3. ADH (water retention)
261
where does Ang2 work in the kidney
PCT to reabsorb Na
262
what 3 things go into osmolarity and what is the equation?
2Na + BUN/2.8 + Glucose/18
263
acute tubular necrosis presents with
muddy brown casts - injured tubules. most common in hospital setting
264
prerenal azetemia is most common in what setting (hospital, outside etc.) and what are some causes (3)
outside the hospital
- hypovolemia
- heart failure
- cirrhosis
265
definition and classifications of AKI (3)
fast deterioration of ability to excrete nitrogenous waste products
1. prerenal
2. acute parenchymal renal disease (vascular, glomerulo, interstitial or tubular)
3. postrenal - obstruction
266
Stage 1 AKIN classification requirements
greater than 1.3 serum creat or less than 0.5 urine output
267
pigmented casts are indicative of
acute tubular necrosis
268
if urine osmolarity and specific gravity are the same as plasma, what does that indicate?
acute tubular necrosis, or some intrinsic renal disease
269
common drugs that cause prerenal syndrome (2)
NSAIDs
| ACE inhibitors/ ARBs
270
causes of ATN (3)
- ischemia
- toxin
- sepsis
271
phases of ATN (3)
1. initiation
2. maintenance
3. recovery (noto all fully recover)
272
definition of oliguria
less than 400mL over 24 hours - indicates a bad prognosis
273
definition of polyuria
over 3000mL over 24
| can be from diabetes insipidus
274
what does BUN/creat ratio over 20 indicate
dehydration, hypovolemia, prerenal issue
275
what causes SIADH (4)
1. hypothalmic increase in ADH production (CNS issue, drugs, pulmonary disease, post op and nausea)
2. increased ectopic production of ADH (oat cell, bronchogenic)
3. potentiation of ADH effect (drugs)
4. exogenous administration
276
what causes euvolemic hypernatremia (2)
BOTH always have to be coupled with low water intake
1. nephrogenic diabetes insipidus (no RESPONSE to ADH)
2. neurogenic diabetes insipidus (no ADH)
277
what are some acquired causes of nephrogenic DI? (3)
1. severe hypercalcemia
2. severe hypokalemia
3. lithium
278
free water deficit equation
= [serum Na+ measured - 1] / [serum Na+ desired] x weight(kg) x 0.6
279
desmopressin
synthetic form of ADH - is antidiuretic but has no vasopressor activity
280
what's the range of urine osmolality?
50-1200 mOsm/kg
281
at what change in EBV does ADH start ramping up
6-8% change in EBV
282
what do you fix first, volulme or water
volume AKA salt
283
3 phases of ATN
1. initiation phase - cloudy swelling
2. oliguric phase - back diffusion and obstructed dilated tubules
3. diuretic phase (regenerated) - inability to concentrate urine as GFR increases
284
in what part of the kidney (medulla or cortex) do you see acute tubulointerstitial nephritis
medulla
| glomeruli are normal
285
bacterial organisms you would expect in ascending pyelonephritis
gram neg:
| E coli, staph saprophyticus, klebsiella, proteus pseudomonas
286
bacterial organisms you would expect in hematogenous pyelonephritis
staph aureaus, salmonella, pseudomonas
more likely to see abcesses
287
what is thyroidization and what is it indicative of
when you have dilated tubules filled with proteinaceous materials and pink hyaline casts - indicative of chronic renal damage
288
what congenital defect is associated with acute pyelonephritis?
vesicoureteral reflux (retrograde flow or urine)
289
what do you see with acute interstitial nephritis? in urine, histo, clinical and gross (4)
- renal failure 1-2 weeks after exposure to drugs (sometimes with fever, skin rash and eosinophilia)
- WBC casts in urine
- enlarged edematous kidneys
- diffuse or patchy infiltrate that spares glomeruli
290
what is acute insterstiital nephrintis caused by? (2)
sometimes due to systemic infection, mostly due to drug-induced hypersensitivity reaction (antibiotics, NSAIDS, diuretics, allopurinol etc.)
291
when do you decide to give someone predisone with nephritis?
if the creatinine doesn't improve after 3-7 days after stopping offending agents, and after you do biopsy
292
when do you see cast nephropathy?
multiple myeloma
293
how do light chains cause acute kidney injury? (2)
direct tubular toxicity and intratubular cast formation
294
what are risk factors for myeloma cast formation and acute kidney injury? (3)
1. hypercalcemia
2. volume depletion
3. IV contrast
295
where do light chains cause problems in the kidney?
light chains are freely filtered, absorbed by endocytosis in PCT usually, but with a monoclonal gammopathy they overwhelm the PCT and end up getting to the DCT and casts form, causing backflow causing increased GFR or rupture of tubule into interstitial and nephritis
296
what is the treatment for adult polycistic kidney disease?
blood pressure control
| tolvaptan(?) bad side effects
297
when do you see muddy brown casts?
acute tubular necrosis
298
what is the urine sodium concetration in prerenal
less than 20
299
SV, HR, SVR, CVP/wedge for hypovolemic shock
SV: low
HR: high
SVR: high
CVP/wedge: low
300
SV, HR, SVR, CVP/wedge for cardiogenic shock
SV: low
HR: high
SVR: high
CVP/wedge: high
301
SV, HR, SVR, CVP/wedge for obstructive shock
SV: low
HR: high
SVR: high
CVP/wedge: low/high (depending on where the obstruction is)
302
SV, HR, SVR, CVP/wedge for neurogenic distributive shock
SV: low
HR: low
SVR: low
CVP/wedge: low
303
SV, HR, SVR, CVP/wedge for anaphylactic distributive shock
SV: high
HR: high
SVR: low
CVP/wedge: low
304
SV, HR, SVR, CVP/wedge for septic distributive shock
SV: depends on if infection is in heart too
HR: high
SVR: low
CVP/wedge: low
305
does hypernatremia cause hypokalemia
no
306
does hypomagnesemia contribute to hypokalemia
yes
307
3 overall categories of causes of hypokalemia
1. transcellular shifts
2. GI losses
3. increases in urinary potassium excretion
308
does metabolic alkalosis lead to hypokalemia
yes
309
4 things that cause potassium shifts into the cell and lead to hypokalemia
most stimulate sodium/potassium ATPase
1. insulin
2. B2 agonists
3. alpha antagonists
4. metabolic alkalosis
310
6 things that cause potassium shifts out of cell and lead to hyperkalemia
1. hyperglycemia
2. B2 antagonists
3. alpha agonists
4. metabolic acidosis
5. increases in osmolality (solute drag with water)
6. exercise
311
does vomiting lead to hypo or hyperkalemia
hypo - vomitting leads to an increase in plasma bicarbonate (because you're losing H+ ions in gastric fluid), which leads to bicarb wasting --> increased distal Na delivery
ALSO volume depletion causes aldosterone increase --> enhanced potassium secretion from distal nephron
312
does hypomagnesemia cause hyper or hypokalemia
hypo - magnesium acts as plug on ROMK backleak channel
313
which genetic defect is similar to giving someone furosemide?
Bartter's syndrome (thick ascending limb transporter defects)
314
which genetic defect is similar to giving someone a thiazide?
Gitelman's syndrome (Na-Cl co transproter in DCT)
315
how can you tell the difference in urine labs between Gitelman's and Bartter's?
G has hypOcalciuria (because knocking out NaCl co transporter stimulates calcium reabsorbtion)
B and hypERcalciuria (stimulates calcium wasting into urine)
316
when do you see U waves on EKG
Hypokalemia
317
what does a ratio of >20 of aldosterone/renin mean
primary hyperaldosteronism
318
what test would you do to diagnose primary hyperaldosteronism
CT abdomen and adrenal vein sampling - look for unilateral adrenal adenoma in CT and look for lateralization of cortisol and aldosterone from one side over the other (both being high would be bilateral adrenal hyperplasia)
319
do thiazides produce hypo or hyperkalemia
hypokalemia
320
do beta blockers cause hypo or hyperkalemia
hyperkalemia
321
3 overall categories of causes of hyperkalemia
1. impaired cell entry
2. increased cell release (rhabdo, hemolysis)
3. reduce urinary potassium excretion
322
does renal failure cause hypo or hyperkalemia
hyper - limited number of nephrons to get rid of potassium
urine output declines, thus distal sodium and water delivery declines
323
what do you see on EKG for hyperkalemia (4)
1. K of 6-7: peaked T waves around
2. K of 7-8: increased PR interval
3. K of 8-9: lose the P wave, widened QRS
4. >9 sine wave pattern
324
what do you give someone with hyperkalemia (4)
1. calcium (stabilize cardiac membrane)
2. D50/insulin (stimulate sodium/potassium ATPase)
3. sodium bicarb (shift into cell via buffering - don't give on dialysis)
4. kayexalate (cation exchanger - enhances K excretion in the gut in exchange for sodium)
325
what syndrome is associated with familial renal cell carcinoma?
Von Hipple Lindau
326
what is the most common subtype of renal cell carcinoma?
clear cell renal cell carcinoma
327
what is the most common grading system for renal cell carcinoma?
Fuhrman- 4 tiered based on:
1. nuclear size
2. pleomorphism
3. nucleolar size
staging using TMN
(tumor size and invasion, nodal, metastesis)
328
what is the most significant risk factor for pladder urothelial carcinoma
tobacco
329
what diagnostic technique do you use to evaluate bladder tumors
CT urogram with contrast or cytoscopy
330
what are the most common bladder cancers
epithelial transitional
331
shistosoma causes what
squamous bladder cancer
332
what is it, if you see fat in a kidney tumor
indicates angiomyolipoma - benign tumor
333
what is the von hippel lindau mutation
AD mutation of gene on 3p25 (upregulate angiogenesis veg-f gene)
retinal tumors, pheo an kidney clear cell = multifocal and recurent
334
what is tuberous sclerosis mutation and presentation (3)
AD mutation on chromosome 9 (hamartin) or 16 (tuberin)
triad:
metnal retardation,
adenoma sebaceum
seizures
335
how to treat kidney tumors
surgery - chemo and radiation are not effective
336
what does clear cell carcinoma look like grossly (3)
1. gold yellow - due to glycogen and fat particles
2. areas of necrosis and hemorrage
3. clear demarcations
337
what does clear cell carcinoma look like on histology
nests of cells with chickenwire capillary network and clear cells
338
collecting duct carcinoma findings
1. highly aggressive
2. malignmant cells form glands
3. prominent fibrotic stroma
339
if you have a kid with abdominal mass and aniridia (messed up iris) what do you think
wilms tumor
340
what does a wilms tumor look like grossly
white grey well circumsribed
341
pathologic characteristics of of wilms tumor
primative looking triphasic:
1. blastemal
2. epithelial
3. stroma
342
what is WAGR syndrome? genetics?
1. Wilms
2. Aniridia
3. Genital anomalies
4. mental Retardation
associated with germline deletion of 11p13 WT1 gene
343
two kinds of bladder tumor architecure
1. papillary (most common) cauliflower like finger-like projections (low or high grade)
2. flat
344
treatment for non-muscle invasive tumors (3)
1. resection
2. BCG (TB vaccine)
3. mitomycin (chemo)
recurrence is common
345
treatment for muscle invasive (2)
1. remove bladder,
| 2. neoadjuvent chemo
346
what foods have a lot of oxalate in them
spinach, dark chocolate, tea
347
what is struvite made from
magnesium-ammonium-phosphate
348
do phosphates for in alkaline or acidic urine
alkaline
349
what stone cannot be seen on xray
uric acid
350
what causes uric acid stones
leukemia, lymphoma and chemo
351
someone who has stones for a long time and is young, what do you think
cysteinuria (can't reabsorb "cola" - cystein ornithine, lysine, arginine)
352
5 categorical causes of secondary htn
1. renal (renal parenchymal, obstruction)
2. renovascular (renovasc htn, athero, aortic coarctation)
3. endocrine (pheo, aldoste, cushing, thyroid, parathyroid)
4. OSA (obstructive sleep apnea)
5. Drugs (NSAIDs, birth control, steroids, sympathomimetics, cyclosporines, EPO, cocaine, alcohol)
353
whats the gold standard for evaluating renovascular secondary HTN
renal angiogram
354
what issue is seen with fibromuscular disease
renovascular hypertension in young women
355
why does nephritic syndrome cause secondary htn
increased sodium retention
356
apparent mineralocorticoid excess cause
glycyrrhizic is an inhibitor of 11 B HSD2 enzyme which converts active cortisol to cortisone
357
pheochromocytoma cause, presentation and test
tumors arise from chromaffin cells of neural crest
present with
headache, weight loss, sweating, palpiitations, pallor, orthostatic hypotension
plasma free metanephrines and catecholamines in plasma, MIBG for extrarenal
358
definition of htn emergency vs urgency
```
emergency = signs of ACUTE end organ damage
urgency = NOT acute end organ damage
```
359
cushing syndrome cause and findings
sustained glucocorticoid excess from ACTH production from pituitary adenoma or lung cancer or adrenal adenoma
see insulin resistance, muscle wasting, purple striae
360
azathioprine mechanism
CYTOTOXIC ANTIMETABOLITE inhibit clonal expansion of lymphocyte population by inhibiting DNA replication
liver cleaves azathioprine to 6-MP, which is converted by lymphocytes to 6-thio-GTP and 6-thio-dGTP via purine salvage pathway --> GTP gets incorporated into RNA, dGTP gets incorporated into DNA, inhibiting lymphocyte function and proliferation
361
azathioprine use (2)
1. high doses prevent organ rejection
| 2. low doses treat autoimmune disorders like rheum arthritis
362
azathioprine adverse effects (4)
older version. is toxic to all rapidly dividing cells:
1. GI tox and
2. bone marrow suppression
3. potentiated adverse with methotrexate
4. potentiated adverse with ACE inhibitor
363
cotisol/glucocorticoid mechanism (2)
inhibit the transcription of pro-inflammatory cytokines
1. bind to receptor, dimerization, binds to promotor region GRE have trancriptional repression of TNF-alpha, IL-1,2,4, and 6.
2. also inhibit mobilization of arachydonic acid and prostaglandin transcription
364
cortisol/glucocorticoid use (2)
1. to prevent tissue allograft rejection
| 2. blocks first-dose cytokine storm cause by Muromonab-CD3 in transplant recipients
365
cortisol/glucocorticoid adverse effects (6)
1. growth suppression
2. osteopenia
3. infection
4. inhibited wound healing
5. hypertension
6. hyperglycemia (esp when combined with calcineurin inhibitors)
366
cyclosporine mechanism
CALCINEURIN INHIBITOR - inhibit clonal expansion and activation by inhibiting intracellular lymphocyte signalling
inhibit IL-2 production by binding to cyclophilin which then binds and inhibits calcineurin -- can't dephosphorylate NFAT to induce IL-2 expression
367
cyclosporine use (2)
1. prevent transplant rejection (dosing requires monitoring signs of rejection = low cyclosporine, or tox = high cyclosporine)
2. autoimmune disorders
368
cyclosporine adverse effects (4)
1. metabolized by Cyp3A (inhibitors like CC blockers, HIV protease inhibitors, allopurinol cause increased cyclosporine levels, inducers like phenytoin, rifampin, phenobarbital lead to decreased cyclosporine levels)
2. renal dysfunction/ nephrotoxicity (dose limiting)
3. hypertension
4. diabetogenic when used with glucocorticoids
369
mycophenolate mofetil mechanism
CYTOTOXIC ANTIMETABOLITE inhibit clonal expansion of lymphocyte population by inhibiting DNA replication - more selective in suppressing immune cells over azathriopirne
hydrolized to active mycophenolic acid in liver, which inhibits enzyme (inositil monophosphate dehydrogenase type 2 IMPDH) in denovo purine pathway, inhibiting DNA syth
370
mycophenolate mofetil use
1. prophylaxis for organ transplant rejection
| 2. autoimmune disorders
371
mycophenolate mofetil adverse effects (3)
1. fewer tox (less GI or bone marrow suppression) because it's selective for B and T lymphocytes, but still present
2. decrease dosage of mycophenolate when using tacrolimus
3. congenital abnormailties - pregnancy loss
372
tacrolimus mechanism
CYCLOSPORINE INHIBITOR - inhibit clonal expansion and activation by inhibiting intracellular lymphocyte signalling
inhibit IL-2 production by binding to FKBP-12 which then binds and inhibits calcineurin -- can't dephosphorylate NFAT to induce IL-2 expression
373
tacrolimus use (1)
1. prevent trasnplant rejection by decreasing IL-2 production
374
tacrolimus adverse effects (5)
1. renal dysfunction/nephro
2. hypertension
3. diabetogenic esp when used with glucocorticoids
4. neurotoxic - tremors, headaches, seizures
5. metabolized by Cyp3A (inhibitors like CC blockers, HIV protease inhibitors, allopurinol cause increased tacrolimus levels, inducers like phenytoin, rifampin, phenobarbital lead to decreased tacrolimus levels)
375
sirolimus mechanism
AKA rapamycin
mTOR inhibitor - prevents T-cell activation and proliferation by inhibiting protein synthesis
binds to FKBP-12 which then binds to mTOR which regularly progresses from G1-S phases -- so you can't activate and proliferate T cells
376
sirolimus use
1. prevent trasnplant rejection
| 2. targeted therapeutic agent for certain solid tumors
377
sirolimus adverse effects (5)
1. metabolized by Cyp3A (inhibitors like CC blockers, HIV protease inhibitors, allopurinol cause increased sirolimus levels, inducers like phenytoin, rifampin, phenobarbital lead to decreased sirolimus levels)
2. dose dependent hylerlipidemia
3. dose dependent hypertension
4. myelosuppression
5. lymphocoele around renal transplantation
378
how does 6-MP get metabolized/inactivated? (2)
1. xanthine oxidase (which is decreased by gout drug allipurinol)
2. TPMT - polymorphic gene - WT works properly, inactive allele doesn't
379
what's the most common induction agent for kidney transplant immunosuppression
thymoglobuin
380
what's the most common maintenenece agent for kidney transplant immunosuppression
tacrolimus
381
thymoglobulin mechanism, use and side effects
rabid derived polyclonal antibody which depletes lymphocytes
used as induction agent and in severe acute rejections
side effects: fever, arhtralgias, aseptic menngitis, marrow suppression, CMV, EBV infections
382
common infections in solid organ transplant patients at <1mo, 1-6mo and >6mo
<1mo = common infections like mRSA
1-6mo = viral infections like CMV
>6mo = less common infections like aspergillus and mucor
383
top 3 reasons people get lung trasnplants
COPD, CF, IPF
384
ABSOLUTE contraindications for lung transplants (8)
1. cancer in the last 2 years (excluding BCC and SCC)
2. dysfunction of another system (heart, liver, kidney)
3. chronic infection (hep C, HIV)
4. chest wall/spinal deformity
5. non-adherence
6. psych condition
7. no social support
8. substance abuse within 6 months
385
lung allocation score goals (3)
1. reduce mortality among patients on waiting list
2. urgency-based prioritization
3. deemphasize the role of waiting time and geography
386
what are the types of lung transplants (3)
1. bilateral (best for suppurative diseases like CF and bronchiectasis)
2. single lung transplant
3. heart-lung transplant (if you have eisenmenger with uncorrectable cardiac anomaly)
387
what do you see with primary graft dysfunction, what do you do
within first 72 hours, reperfusion injury - alveolar damage and hypoxemia - most patients recover, but monitor
388
what do you see with acute rejection, what do you do
within first 3 months
see inflammatory infiltration, decline in FEV and FVC
give steroids
389
what do you see with chronic rejection, what do you do
within first 5 years
bronchiolitis obliterans. irreversible decline in FEV1, don't do well, no treatment - major cause of mortality and morbidity
390
post-transplant lymphoproliferative disorder cause, clinical, treatment
B cell lymphoma that's EBV related
see CXR nodular density within first year after transplant
treat by REDUCING immune suppression
391
mortality is better or worse for lung vs kidney trasnplant
worst for lung
392
amygdala and aging
amygdala enhance positive emotional memory and allow older adults to disengage from experiences of regret - dependent on exercise, social interaction and environmental enrichment
393
frailty components (5)
1. reduced 2. walking speed
3. longer time to perform ADL
4. weight loss (more than 10% in the last 6 months)
5. muscle wasting
394
cardiac aging and cardiac output factors (3)
1. left ventricular stiffness (decreases preload and ejection fraction)
2. decreased aortic compliance (increased afterload, decreased ejection fraction)
3. altered calcium (decreases myocardial contraction and HR, decreased ejection fraction) and decreased CO
395
normal renal aging (4)
1. sclerosis
2. atrophy
3. loss of glomeruli and total mass
4. reduction of functional reserve
396
what do you need to do as a physician for decreasing changes of renal failure in older adults (2)
1. encourage fluids to avoid infection - beware of decreased fluid intake
2. be careful what you prescribe
397
pulmonary homeostenosis and aging (6)
1. FEV1 declines
2. decreased vital capacity
3. enlargment of alveolar ducts due to loss of elastic tissue
4. calcified constrochondral cartilage - less chest expansion
5. abdominal muscles used in respiration - only effective while standing
6. coughs less vigorous
7. cilia is less effective
398
what do K antigens do
make bacteria more virulent in urinary tract
399
what do fimbrae do
make bacgeria more adherent to vaginal/uroepithelial cells (T type, type 1)
400
what is aerobactin
iron scavenging protein in bacteria
401
where is antibody response in urinary tract?
upper tract - pre-existing, but not protective
402
epidermidis vs saprophyticus patients
sapro is more female, more young, more common, more symptomatic, more outpatient, rarely relapse and are often antibacterial sensitive
403
candiduria
endoegnous flora
can be associated with cystitis -associated with DM and foley
can get hematogenous
if symptomatic treat with fluconazole (some are resistant to fluconazole though - cruzii and fibrata)
404
what is the definition of chronic kidney disease (2)
kidney damage for >3 months with structural/functional abnormalities with/without decreased GFR
OR
GFR <60mL/min per 1.73m for >3mo with or without kidney damage
405
populations at risk for CKD (2)
older age
african americans 4x more likely (have APOL-1 and MYH-9 loci)
406
cystatin c
to measure AKD and somewhat CKD
407
CKD staging - axes
A1-3 = albuminuria categoies (<30 to >300)
G1-G5 = GFR (>90 to <15)
408
how may people >20 years have CKD
20 million
409
how to get patients to inhibit RAAS to reduce GFR (3)
1. low protein dient
2. ACE/ARB
3. aldosterone antagonist
410
how to reduce proteinuria (2)
1. ACE/ARB
| 2. statin
411
what medicines should you avoid in chronic kidney disease
1. metformin (causes lactic acidosis)
2. IV contrast
3. NSAIDs
4. herbal medications
5. aminoglycoside antibiotics (-mycins)
412
calcium, phosphate and magnesium in CKD
hypocalcemia
hyperphosphatemia
hypermagnesemia
413
two broad categories of health disparities
health (differences in morbidity and mortality across all disease categories)
and
health care (access, utilization, quality and outcomes)
414
disparity = difference?
disparities are differences that should not happen -that would not occur through normal physiology
415
RTA type 1
most severe phenotype = defect in distal tubule, impaired proton excretion, urine pH >5.3 (no room for nephron to kick out protons)
416
RTA type 2
less severe phenotype = defect in proximal tubule, HCO3 wasting, variable pH depnding on level of HCO3 wasting
417
RTA type 4
issue with aldosterone deficiency or resistance
418
anion gap metabolic acidosis
C- citrate
U- uremia
T- toluene
E- ethanol
```
D- diabetic ketoacidosis
I- iron
M- methanol
P- paraldehyde
L- lactate
E- ethylene glycol
S- salicylate
```
ALL are ingestions except:
- uremia
- ketoacidosis
- lactic acidosis
419
what equation to use to see if there's more than one metabolic distrubance
delta gap = change in AG/change in bicarb
every time anion gap goes up by1, your bicarb should go down by 1 --> normal delta gap is between 1 and 2
>2 coexisting metabolic alkalosis (bicarb is higher than it should be)
<1 coexisting non-gap metabolic acidosis - diarrhea and lactic acidosis for example (bicarb is lower than it should be)
420
how to tell if metabolic acidosis is due to diarrhea or renal tubular acidosis
urine AG = urine (Na + K) - Cl
if diarrhea and kidenyes are functioning, urine AG should be negative
if RTA, urine AG is positive - can't get rid of enough Cl in urine
421
anion gap equation
= Na - (Cl + bicarb)
422
how can you tell if there's appropriate compensation for a metabolic acidosis?
pCO2 = 1.5 (bicarb) + 8 +/- 2
(winter's formula)
too high much means you also have a respiratory acidosis
423
how can you tell if there's appropriate compensation for a metabolic alkalosis?
pCO2 = 0.7 + (change in bicarb) + 40
424
for acute respiratory acidosis, what happens to bicarb when CO2 changes
every change in CO2 by 10 causes a change in bicarb by 1
425
metabolic alkalosis is usually seen with what chlorine and potassium levels
hypochloremia and hypokalemia
426
what things generate a metabolic alkalosis (3 categories, 10 total)
GI proton losses:
1. vomitting
2. nasogastric suction
3. villous adenoma
4. congenital chloridorrhea
Renal proton losses:
5. diuretics (loop and thiazide)
6. transport defects
7. mineralocorticoid excess
8. posthypercapnia
addition of bicarb:
9. hypercalcemia
10. blood transfusion
427
what things maintain a metabolic alkalosis (4)
1. hypovolemia
2. hypochloremia
3. hypokalemia
4. mineralocortiocoid excess
428
normal compensation for metabolic alkalosis
respiratory acidosis - hypoventilation
429
what ion do you look for in urine in metabolic alkalosis
Cl
if urine Cl is low, give them Cl (sodium chloride or potassium chloride if hypokalemic)
(they're usually volume depleted)
if urine Cl is high, probably volume exapnded so you have to treat underlying issue
430
if urine clhoride is low in metabolic alkalosis and blood pressure is HIGH what do you do next
look at RENIN
```
if renin is high, and cortisol is high:
- cushings
if cortisol is low:
- renal artery stensosi
- malignant htn
, renin secreting tumor
- accellerated htn
```
if renin is low, could be
1. primary aldosteronism
2. licorice abuse,
3. liddle's syndrome
431
if urin chloride is low in metabolic alkalosis and blood pressure is LOW or NORMAL, what do you think
1. bartter's syndrome
2. gitelman's syndrome
3. diuretic use
432
if urien chloride is low with metabolic alkalsosi, what could it be
1. gastric fluid loss (vommitting)
2. non-reabsorbable anion delivery
3. post diuretic use
4. post hypercapnea
5. villous adenoma
6. congenital chloridorrhea
433
what does pregnancy cause (acid-base)
chronic respiratory alkalosis
434
the two ways you can lose bicarbonate
- big tubule (diarrhea = same number of unmeasured anions, higher Cl)
- small tubule (tubular disfunction RTA2, normal anion gap)
435
mechanisms of developing metabolic acidosis
1. acid overload (increased acid production or addition - HCl or NH4Cl)
2. decreased acid excretion (renal failure or RTA1)
3. loss of bicarb ions (diarrhea or RTA2)
436
causes of normal anion gap metabolic acidosis
renal issues:
1. proximal RTA
2. distal RTA
3. hyperkalemic distal RTA
4. early renal failure
GI issues:
5. diarrhea
6. small bowel losses
7. ureteral diversions
8. anion exchange resins
9. ingestion of CaCl2
acid infusion:
10. HCl
11. Ariginine HCl
12. Lysine HCl
437
what is the relationship between insulin and potassium secretion?
insulin deficiency causes loss of potassium
438
effectiveness vs efficacy
```
efficacy = in study
effectiveness = in real world
```
