Muster Week 2 Flashcards
1
Q
Filtered substances can be ____ or ____
A
REABSORBED or SECRETED as needed to maintian homeostasis
2
Q
Amount filtrate into nephron PT
A
125 mL/min
3
Q
SECRETION
A
peri-tubular capillary to lumen
4
Q
REABSORPTION
A
lumen to peri-tubular capillary
5
Q
proximal tubule is made of…
A
proximal tubule cell SINGLE CELL LAYER (but still cell membrane)
6
Q
____ of all the filtered solute and water are reabsorbed within the proximal tubule!
A
2/3
goes in at 300 mosmol –> leaves as 300 mosomols = ISO-OSMOTIC
“literally sucking up what just put into it”
7
Q
Mechanisms to move substances
A
- diffusion (generally down a gradient)
- channels
- transports (uniporters/multiporters) (active, 1* or 2*)
8
Q
Primary active transport requres ______
A
ATPase, energy
9
Q
Secondary active transport
A
one of solutes moves down EM/conc gradient, which drives other
“drag other along for the ride”
10
Q
stoichiometry drives _____
A
charge difference
11
Q
basolater Na/K transporter is ________ transport
A
ACTIVE transport
requires energy
ONLY ON BASOLATERAL (serosal, anti-luminal, blood side)
12
Q
luminal Na+ channel is
A
PASSIVE
13
Q
What is K+ doing?
A
RECYCLING
allows pump to keep moving/working
14
Q
Na-glucose trnasporters are also known as…
A
SGLT (sodium-glucose linked transporters) in two flavors, 1 and 2
***90% of glucose reabsorbed in PT occurs via SGLT 2 (1:1)
15
Q
2* active transport is regulated by:
A
- increased CO2
- increased angiotension II
- increased SNS drive
- decreased pH
= ACIDOSIS
16
Q
Na/H pump responds directly to ______
A
acidosis
17
Q
_____% of glucose is brought across at luminal border by _____
A
100% of glucose is brought across luinal border by SGLT 2 = NO GLUCOSE IN URINE
18
Q
___, ___, and ___ are all being pumped UP their EM gradient
A
glucose, a.a.s, phosphorus pumped UP EM gradient by 2* ACTIVE TRANSPORT
- all facilitated by Na* transport (symporters)
19
Q
High Na+ in interstitium drives _____
A
Na+ concentration gradient into peritubular capillaries
20
Q
transport maximum (Tm)
A
Na+/glucose transporter saturation point…additional glucose will NOT be able to be reabsorbed and will REMAIN IN URINE
~15mM glucose
21
Q
glucosuria
A
when Tm (or glu in urine?) reaches about 15mM = ABNORMAL
not a test for DM
22
Q
Why isn’t glucosuria test for DM?
A
Becuase Tm is transport mediated, so could have totally normal serum [glu] but glu in urine = SOMETHING IS WRONG WITH TRANSPORTER IN PT (not just high glu everywhere)
23
Q
osmotic diuresis
A
Na/glu transporter has reached Tm –> excrete rest of glu out –> H20 follows –> osmotic diuresis
24
Q
Cl- transport, think
A
Cl- recycling
formate recycling
“that’s just the way Cl- is handled” it is recycled using FORMATE = FORMATE ANTIPORTERS = formate is recycling too
and PARACELLULAR TRANSPORT through tight junctions
25
late section of PT
- formate anti-porters
- favorable concentration gradient of Cl- for transcellular movement
- EM gradient allowing some para-cellular movement of sodium as well
26
CA is present two places
1. brush border
| 2. in cell
27
HCO3- transport
1 DESTROYED: 1 RECLAIMED (put back in blood)
= BICARBONATE REABSORPTION/RECLAMATION
bicarb is created and put back into the blood stream
28
CA
CO2 + H20 --> H2CO3 --> HCO3- + H+
= makes bicarb and protons
the reaction occurs without carbonic anhydrase (CA) but CA cranks it up 100x
29
Na/HCO3- symporter
on capillary bed side --> 3 HCO3-: 1 Na+ BOTH GOING OUT
| = puts bicarbonate back in blood
30
If PT defect...
see in urine:
- BICARB (ACIDOTIC)
- PHOSPHOROUS can't be reclaimed
- VITAMIN D also
31
H20 transport in PT
1. diffusion (minor player)
2. aquaporins
3. paracellular transport
*for all solute reabsorbing, water follows --> no change in osmolality
32
ATN
ACUTE TUBULAR NECROSIS
- damage to PTs --> Na+, Cl-, bicarb, glu = everything in pee that PT isn't taking up
- see casts
33
As fluid leaves the glomerulus --> slight increase in oncotic pressure (filtration of solute and water)
slight increase in oncotic pressure (filtration of solute and water)
34
hydrostatic pressure within capillary drops due to
resistance
35
Net filtration pressure of capillary uptake
forces of filtration - forces of reabsorption
(P pc + PI i) - (P i - PI pc)
(20 + 6) - (33 + 3) = -10mmHg
NEGATIVE 10mmHg = OPPOSITE OF FILTRATION = REABSORPTION
36
____% of Na, Cl, H20, reabsorbed by end of PT
66%
37
____% glucose reabsorbed by end of PT
100%
38
____% HCO3 reabsorbed by end of PT
80%
39
Why need to filter 180L/day?
We are putting toxic waste metabolites into urine, NEED THIS COPING MECHANISM TO RID TOXINS
(otherwise would be very pointless and excessive)
40
Not all substances filtered have channels or transports, so they must either:
diffuse across cell membrane OR be excreted
41
Polar substances
have CHARGE
42
Non-polar substances
have NO charge
43
Polar substances' fate
no transporter/channel/diffusion --> trapped in lumen --> "PEE OR POOP IT OUT, THAT'S IT!"
44
Non-polar substances' fate
Non-polar CAN diffuse across cell membrane --> reabsorption
Ex: O2, steroid hormones, CO2, cholesterol
45
If given a toxic substance, would you want it to be polar or non-polar?
You would want it to be POLAR SO CAN EXCRETE IN URINE/POOP
46
Liver transformation is...
give dursg that are non-polar --> liver --> cyp450 --> polarized drug --> can excrete
47
If interaction to CYP450...have to do what to dosing?
Interaction with CYP450 --> decreased ability --> decrease dosing
48
WOA and WOB are both:
secreted AND reabsorbed
49
WOA and WOB we WANT to keep
monocarboxylic acids: pyruvate, ketone bodies, lactate
50
Keep WOA and WOB by...
adding carboxylate to them --> kidney recognizes carboxylic group --> allows to attach to transporter --> gets into cell --> pumped out
***this pump can become saturated, HAS A TM
51
OAT and OCT
organic anion transporter
organic cation transporter
*DEPENENT ON BOUND TO ALBUMIN
active transport
52
WOA and WOB transport into lumen...
facilitated diffusion
53
WOA and WOB into cell from blood...
active transport (OAT and OCT)
54
WOA and WOB (as MCA's) into cell...
Na+/MCAs symporter
55
MCA's back into capillary...
MCA transporter
56
orthostatic hypotension is a sign of ________
volume depletion
57
Key functions of Loop of Henle
1. reabsorbs 25% of filtered sodium
(add to 66% Na reabsorbed in PT)
2. Na is reabsorbed IN EXCESS of water = JUST THE SOLUTE = INCREASES [H20]
--> allows for the excretion of urine with osmolality that is DIFFERENT than plasma
58
Parts of nephron NOT permeable to H20
Thin and thick ascending limbs of Loop of Henle, distal tubule
NO AQUAPORINS
59
PT mOsms
deep medullary space mOsms
end of thick ascending limb mOsms
```
PT: 300 mOsms
Deep medullary space: 1400 mOsms
(huge draw for H20 out of the tubule)
(bottom of loop)
End of thick ascending loop: 100 mOsms
(ascending not permable to H20, but Na+/K+/CL- pump)
(top of loop)
```
60
Thick ascending limb
channels set up nice gradient
| - Na/K/2Cl carrier!
61
Important functions of Na/K/2Cl carrier:
1. reabsorbs 20% of filtered Na!
(add to 66% from PT, 25 from loop of henle!)
2. all sites MUST be occupied
3. Na+ reabsorption is NOT linked to organic solutes (glucose, phosphorous)
4. affinity for Na+ and K+ is VERY HIGH --> Cl- is RATE LIMITING
62
Na/K/2Cl blocker
Lasix (furosemide)
63
Lasix indicated for
CHF
NaCl retensive patients
-give along with low Na+ diet so can affect this 25% reabsorption and make a difference
64
Na/K/2Cl transporter mutation
Bartter syndrome
- 25% more Na, K, and 2Cl are hitting urine than should
- genetic mutation
65
Bartter syndrome
- 25% more Na, K, and 2Cl are hitting urine than should
- genetic mutation
- present EARLY IN LIFE
- growth retardation
- mental retardation
- VOLUME DEPLETION with LOW BP
- HYPOkalemia
- METABOLIC ALKALOSIS
- normal or elevated urinary calcium excretion
66
Why get elevated urinary calcium excretion in Bartter syndrome?
paracellular Ca2+ transport can only work in Na/K/2Cl pump works
67
Distal tubule key features
1. reabsorbes about 5% of filtered sodium
(add to 66% in PT, 25 in loop of henle, 20% in ascending limb!) by NA-CL PUMP
2. tubular reabosroption of Na+ varies with Na+ delivery (limited if don't have enough Na+)
3. iMPERMEABLE TO WATER so contributes to URINARY DILUTION
4. contribues to calcium reabsorption
68
NaCl transporter mutation
Gitleman syndrome
| *better than mutation in Na/K/2Cl transporter because this one only takes care of 5% more Na+ reabsorption
69
Gitleman syndrome
- genetic mutation in NaCl transporter
- normal BP
- METABOLIC ALKALOSIS
- HYPOcalciuria
- HYPOmagnesemia
- HYPOkalemia
70
Na/Cl transporter blocker
hydrocholorothiazide
| *will improve HTN but not to same degree as Lasix
71
Can manipulate kidney Na+ reabsorption for HTN tx because
Na+ = BV = BP
PIVOTAL
72
The collecting duct key features:
1. variable sodium reabsorption
* **FIRST AREA that is DIRECTLY CONTROLLED to DETERMINE URINARY ELECTROLYTE CONCENTRATION
2. principal cell: BIG KAHUNA BURGER
3. intecalated cell
73
primary role principal cell
BIG KAHUNA BURGER
- contributes to Na, Cl, and K reabsorption/excretion
- ENaC (epithelial Na+ channel)
- RMPK (renal outer medullary K+ channel)
74
primary role intercalated cell
- H+, HCO3-, and K+ reabsorption/excretion
75
Of filtered load of Na+, ____% is controlled
5%
76
If reabsorb 4.9% of controlled amount filtered load of Na+, excrete:
excrete 0.1% of filtered load = 1g Na+ (25mM)
77
If reabsorb 0% of controlled amount filtered load of Na+, excrete:
excrete 5% of filtered load = 50g Na+ (1250mM)
78
Primary mechanism of controlling salt reabsoption (that 5%) (and K+ secretion) in principal cells is via...
the hormone ALDOSTERONE
79
Primary regulator of this secretion of aldosterone is...
angiotensin I and ultimately, angiotensin II
80
RAAS SYSTEM
RENIN --> ANGIOTENSIN I --> ANGIOTENSIN II --> ALDOSTERONE
| and ADH
81
3 primary physiologic signaling pathways that stimulate renin release:
1. SNS (NE)
2. decreased stretch in afferent arteriole
3. decreased Cl- delivery to macula densa
82
Renin release stimulated by these clinical manifestations:
1. hypovolemia
2. low Na diet
3. low body NaCl
4. anything that causes high SNS
83
Primary actions of angiotensin II
1. ULTIMATELY stimulates ALDOSTERONE
2. systemic vasconstricotr
3. stimulates PT reabsorption of Na+
4. increases SNS
84
Aldosterone and principal cell key points:
1. aldosterone stimulated by angiotensin II
2. lipophilic so FREELY crosses cell membrane
3. binds to intracellular Rec --> ultimately INCREASES TX OF CELLULAR PROTEINS
4. proteins INCREASE ACTIVITY or NUMBER of both the luminal Na+channel ENAC and Kchannel ROMK and basolateral Na/K/ATPase
*renin responding to low Na+ state --> aldosterone --> more doorways --> reabsorbs as much Na+ as possible
85
aldosterone causes
- increased Na- reabsoprtion
| - K secretion
86
aldosterone stimulus for release
- low Na+ states
| - high K+ states
87
K+ sparing diuretics:
1. amiloride
| 2. triamterene
88
disease of upregulation of ENaC
Little's syndrome
- ENaC always on --> ramp up insertion when stimulated by aldo --> reabsorbing Na+ soo much --> no response to aldo any longer
- present: Na+ sensitive HTN
89
FENa
excreted / filtered x 100
90
clearance
excretion rate / plasma concentration
91
Cr cl in ____ Na+
high Na+
| = trying to clear
92
NaCl = ____
volume
| water follows
93
GFR (creatinine clearance) varies with salt intake:
high salt --> increased filtered load of Na+ --> increased Na+ excretion
94
aldosterone is stimulated by ___ salt stores
low salt stores
| high salt --> reduced aldo --> fewer ENaC channels to reabsorb Na+ --> Na+ excretion increases
95
PT, Na+/H+ antiporter is regulated by RAAS:
high salt --> reduced renin --> reduced Na+ reabsorption --> Na+ excretion increases
96
Two primary functions of K+
1. cell metabolism (protein and glycogen synthesis)
2. (ratio of intracellular/extracellar potassium) PRIMARY DETERMINANT OF RMP (ie the necessary state for generation of APs)
97
___% of K+ is stored intracellularly
98%
98
key regulators of immediate/short term extracellular K+
1. insulin (activate Na/K ATPase, promotes SKmus uptake)
| 2. catecholamines (beta-2 receptors stimulate Na/K ATPase)
99
cell and channels that facilitate renal excretion of K+
```
PRINCIPAL CELL
Na/K ATPase pump
ROMK channels (K+)
ENaC channel (Na+)
BK channel (K+)
```
100
location of K+ reabsorption and contribution of each tubular segment
PT: 55-67% via tight junctions
thick ascending limb/loop of henle: 25%
principal cell in distal tubule: 10%
alpha-intercalated cell in collecting: 10% (actively reabsorbed)
101
location of Ca++ reabsorption and contribution of each tubular segment
PT: 65% paracellular across tight junctions
thick ascending limb/loop of henle: 20-25% paracellular
distal tubule: 10% transcellular
102
actions of hormones that stimulate K and Ca secretion
ALDOSTERONE
1. increases activity of Na/K ATPase pump
2. increases presence of ROMK channel
3. occurs in normal or mildly elevated K+ (directly)
PTH
1. directly release Ca++ from bones
2. increase from kidneys
3. activates increased absorption of Ca++ in gut
***increased angiotensin II activates increase in aldo
103
clinical stimuli of hormones that stimulate K and Ca
HIGH K+ STATES/DIET: aldo secreted, also BK channels open (two channels facilitating excretion of K)
LOW K+ DIETS: limited stimulation of aldo, no activity of BK channel, limited/decreased presence ROMK
104
actions of PTH on bone
a. DIRECTLY stimulates immediate release of stored skeletal Ca++ ==> increase serum [Ca++]
b. stimulates bone reabsorption (preserve trabecular bone at expense of cortical bone)
* this DIRECTLY releases PO4- as well as Ca++
105
actions of PTH on kidney
a. increased production of ACTIVATED VIT D
* this increases gut reabsorption of Ca++
b. increases Ca++ reabsoprtion
c. DECREASES renal PO4- absorption (INCREASES EXCRETION/SECRETION PO4-) --> activates make more vit D
106
actions of PTH on intestines
a. increased activated VIT D from kidney --> ULTIMATELY increases gut reabsorption of Ca++
107
cellular mech of Ca++ reabsorption
1. activated PTH
2. stimulates more Ca channels to open (from lumen)
3. Ca++ NEEDS TO BIND TO CALBINDIN
4. Ca++ through calcium ATPASE
108
difference between ROMK and BK channels
ROMK: ALDO increases presence RMOK
*inhibited by Mg++
BK: always there, not usually open
**ONLY OPEN WHEN HAVE LOTS K+ THAT NEEDS TO GET OUT (high K+ states = diets)
109
clinical situation when ROMK channels present
volume depleted
| --> ang II --> aldo --> ROMK --> K out to lumen
110
clinical situation when BK channels present
d
***BK channels NOT present: low K+ diets
111
clinical presentations/dz when all intracell K suddenly released
- digitalis OD
- rhabdomyalisis (breaks down SK muscle, which holds K+_ --> release K
- crushed SK muscle
- femoral clot --> opened --> K+ flooded = REPERFUSION = hyperkalemia --> renal failure
112
control K by:
1. distributing between spaces (hiding it)
| 2. control excretion
113
factors that regulate the Na/K ATPase pump
1. insulin (eat --> increase insulin --> activate pump --> increase K in)
2. catecholamines
3. plasma K
4. exercise --> sudden increase K released from myocytes
5. cell breakdown
6. chronic diseases
114
other factors that regulate K in short term
1. plasma concentration: cellular uptake increased when serum K is up
2. exercise: myocytes release K during exercise
3. pH: increase in systemic H+ (metabolic acidosis) --> H+ into cells --> K+ out --> hyperkalemia
115
sequelae of active reabsorption of K+ in alpha intercalated cell
- K+ is exchanged for H+ ====> free floating H+ in lumen = ACIDIC PEE
- lots of H+ must be processed reabsorb K+
- also requires the reabsorption of bicarb!
= hard work to reclaim K+, has a price (acidic urine, increased HCO3-)
116
___% of all Ca++ bound to _____
40% of all Ca++ is bound to ALBUMIN
117
___% of Ca++ is bound to other stuff
10% (like phosphate, citrate)
118
___% of Ca++ is available as ionized Ca++ (free calcium) (unbound)
50%
- this is the amount Ca++ (free calcium) body is trying to manage
- PTH responds to free calcium, not total body calcium
119
You eat _ mM calcium a day, but only absorb ___ mM
eat 20mM a day, only absorb 4mM
120
risk factors for calcium oxalate stone formation
- high salt diet
- maybe calcium supplements
- reducing dietary calcium can increase stone formation...
121
reduced iCa++ stimulates production of...
PTH
122
primary hyperparathyroidism
```
increase in PTH = ROUGE PTH always on
(separate from sensing Ca++)
- trashes bone --> increase Ca++ release
- increased PO4- excretion --> decreased [PO4-]
- increased gut absorption
- increased vit D
- serum [Ca++] high
```
123
other reasons have increased Ca++, decreased PO4-, but normal/unchanged PTH
- cancer (mimics PTH)
| - granulomatous disease (converts + vit D --> so much calcium with elevated vit D) (eg sarcoidosis)
