Potassium homeostasis Flashcards
1
Q
normal range of K+ in ECF plasma:
A
3.8-5mM
2
Q
[K+] cell conc:
A
~140mM
3
Q
resting potential of nn and mm cell determined by:
A
ratio of ECF and cellular K conc
- when cells at rest (btw APs) cell membrane has greater permeability to K than any ion
4
Q
[K] ECF: 3 mM
A
- hypokalemia (-103 mV Nernst potential (Ek))
- membrane potential (Em) hyperpolarised
5
Q
[K] ECF: 4 mM
A
- normal (Ek= -94 mV)
- membrane potential (Em) normal
6
Q
[K] ECF: 7 mM
A
- hyperkalemia (Ek= -80mV)
- membrane potential (Em) depolarised
7
Q
[K] ECF: if below 3 mM or above 7 mM chances increase of
A
- potentially fatal arrhythmias
- when [K] ECF outside normal range, heart produces abnormal ECG traces
8
Q
symptoms: hypokalaemia
A
- skipped heart beats/ palpitations
- fatigue
- mm weakness
- spasms, tingling, numbness
9
Q
symptoms: hyperkalaemia
A
- nausea
- slow/ weak irreg pulse
- sudden colapse due to arrhythmias
- esp dangerous
10
Q
K: overview
A
- K from food moves rapidly from GIT to ECF
- exercise releases K into ECF during repolarisation phase of AP in skeletal mm
- K ECF is low, addition of K in meal during whole body exercise/ meal dangerous changes to mem potential
11
Q
K: meal rich in fruits/ veggies
A
- K in ECF ~65-70 mM
- rich meal may 2x this
- need rapid mechanism to combat
- shift K into cells as soon as enter GIT
12
Q
K: sink for K
A
- most of body K in skeletal mm
- liver also important site for K buffering
- K conc inside cells v high, K entering from ECF will make lil diff to mem potential
13
Q
K: btw meals
A
- K released from cells, excreted by kidneys
14
Q
K: kidneys sig
A
- control body content of K, is too slow to stop rapid entry of K into mm
- rapid moving K into cells + slower excretion by kidneys = K homeostasis
15
Q
K: fasting/ v low K diet
A
- all K entering in kidney will be reabsorbed
- but K still lost in stools and sweat
- then skeletal mm will donate K to ECF to maintain [K]ECF
16
Q
translocation of K: btw ECF and cells
A
- Na/K exchange pumps on all cells
- move 3x Na out/ 2 K into cell
- both ions moving up electrochemical gradient = ATP needed
- pump protein also acts as ATPase, energy from 1x ATP is used to power each exchange cycle
- exchange is highly regulated to maintain constant [K]ECF
17
Q
translocation of K: feedback/foward sys?
A
- feedback relied on error signal to change controlled variable
= feedforward as don’t need error, fast effect as dangerous is change in [K] ECF
18
Q
translocation of K: during a meal, insulin
A
- special nutrients (esp glucose) and electrolytes
- detected by GIT ‘taste receptors’ release incretins (GLP-1: glucose dependent insulin tropic hormone) signal for insulin release before glucose enters blood
- insulin: uptake of glucose into cells, stimulated Na/K pump
- feedforward activates translocation of K into cells before bulk of K from meal enters ECF
- insulin release when glucose rises in plasma further increases K uptake
- high plasma K conc will directly stimulate insulin release: depolarisation of membrane of pancreatic ß cells
19
Q
translocation of K: short term K deprivation
A
- inhibits ability of insulin to promote cellular K uptake by pump
- good for preventing hypokalaemia after carb rich, K poor meal
20
Q
translocation of K: high [K]ECF and aldosterone
A
- also stimulate Na/K pump
- only in extreme conditions when normal feedforward sys failed to maintain normal lvls of K conc in ECF
21
Q
translocation of K: whole body exercise
A
- at high work rate
- K conc ECF increases, stimulates Na/K exchange pump
- increased plasma Ad conc during exercise also stimulate pump
- counteract loss of K from contracting mm cells
22
Q
control whole body K: by kidney
A
- input: diet
- output: digestive tract, sweat, kidneys
- ## only renal excretion of K is controlled, kidneys ensure K output = input so whole body K constant
23
Q
control whole body K: rate of excretion equation and wat is reg?
A
excretion rate = filtration rate - reabsorption rate + secretion rate
- reabsorption, secretion reg
24
Q
control whole body K: why controlled secretion vital
A
- K filtered at low rate
- due to low conc in plasma
- normal-high K diets, lrg amounts must be excreted
25
control whole body K: K depletion of filtered load where, un/reg? and excretion
~85% of load absorbed into proximal tubule, LOH, process largely unreg
- almost all rest absorbed by distal tubule, collecting duct so ~1% of K in filtered load excreted
26
control whole body K: reabsorption of K
- highly reg, by intercalated cells
- make up wall of nephron w Na/K pumps on BASOlateral mem
- K transported into cells
27
control whole body K: K into cells
- from tubular fluid by K/H antiport (2º active transport) on LUMINAL mem
- K moves DOWN electrochemical grad through channel into ECF
28
control whole body K: when is secretion not present
- when K conc in body lower than normal
29
control whole body K: normal/high K intake
- 85% filtered load still reabsorbed in proximal tubule and LOH
- reabsorption greatly reduced
- amount of K =15-80% in glomerular filtrate secreted into distal tubule, collecting duct and excreted
30
control whole body K: principal cells have, secretion
- of collecting duct have K channels (ROMK) on LUMINAL mem
- secretion from active transportation via ROMK channels in principal DOWN electrochemical grad via ROMK channels
- K shifted from ECF to tubular fluid for excretion
31
control whole body K: aldosterone
- stimulates K secretion into tubular fluid by principal cells of distal tubule, collecting duct
- high [K]ECF depolarises plasma mem of aldosterone prod cells in adrenal cortex
- opens voltage gated Ca channels
- Ca activates Ca-calmodulin-dependant protein kinases that stimulate aldosterone prod
- is steroid hormone, can't be stored in cell
- release directly related to rate of prod
32
control whole body K: membrane transport in distal tubule, collecting duct reg by
- aldosterone
- travels in blood bound to carrier protein
- crosses basolateral mem of cell: distal tubule, collecting duct
- hormone bind to receptor within cell of distal tubule, collecting duct
33
control whole body K: when aldosterone binds in cell
- hormone binds to receptor in cell, moved into nucleus to bind to HRE of several genes
- rate of transcription of RNA of many proteins increased (eg. Na/Cl cotransport (NCC) of distal tubule, Na (ENaC) and K (ROMK) channels on LUMINAL mem of principal cells of collecting tubule, collecting duct)
- prod of Na/K exchange pumps, proteins involved in ATP prod within mitochondria also upreg
34
control whole body K: result of aldosterone changes
- changes to increase reab of Na and secretion of K
- these processes not directly linked entry of Na into cells of collecting duct produces electrical grad facilitating exit of K so effective secretion of K required reab of Na in region of nephron
- aldosterone inhibits K reab by intercalated cells of collecting duct
35
regulation of K secretion, reabsorption: when [K]ECF is increased
- aldosterone lvls rise
- causing changes in transport processes in connecting tubule, collecting duct
- would promote both K secretion through ROMK channels, Na reab through ENaC
36
regulation of K secretion, reabsorption: problem w K secretion and Na reabsorption
- when K is secreted, body Na and ECF vol would be altered (aldosterone paradox)
- but if upstream (distal tubule) NCC was inhibited, less Na would be reab in distal tubule, balancing increased reab through ENaC in collecting duct
- Na reab, water follows (osmosis) slowing Na reab through NCC would increase flow rate in collecting duct
- favouring K secretion through ROMK
37
regulation of K secretion, reabsorption: for K secretion but no excess Na reab
- NCC needs to be inhibited
- but aldosterone stimulated NCC vs inhibiting it
- but studies: effect of aldosterone on NCC overriden by high [K]ECF acting via WNK protein kinases within cells of distal tubule
38
regulation of K secretion, reabsorption: low K diet
- aldosterone lvls drop
- K secretion stopped
- aldosterone inhibits reab of K by intercalated cels (collecting duct) so falling lvls aldosterone allow cells resume function of reab K, so virtually all K filtered into nephron reab
39
combined reg of ECF vol and whole body K by kidney: total body Na determines?
- plasma vol
| - bP
40
combined reg of ECF vol and whole body K by kidney: low plasma vol activates and effect
- RAAS sys
- prod of angiotensin II -> cause release of aldosterone
- both these hormones affect Na, K transport in distal nephron
- angiotensin II and aldosterone stim reab of Na through NCC
- angiotensin II overrides activation of ROMK by aldosterone
- despite elevated aldosterone lvls, lack of open ROMK channels reduce flow of water, Na in collecting duct = ensure K secretion not increased while Na reab by NCC
- opposes fall in plasma vol
41
combined reg of ECF vol and whole body K by kidney: plasma vol low, [K]ECF increased
- both changes reinforce to cause lrg release of aldosterone
- aldosterone overrides inhibitory effect of angiotensin II on ROMK and NCC inhibited directly by high [K]ECF and increased secretion of K through ROMK
42
combined reg of ECF vol and whole body K by kidney: constant values of total body Na, K maintained by, which transporters
- aldosterone
- angiotensin II
```
direct effect of [K]ECF on:
- NCC
- ENaC
- ROMK
in distal nephron
```
43
diuretics: most common, effective class to treat hypertension
- thiazides
44
diuretics: thiazides features
- promote diuresis (decrease ECF vol) by inhibiting NCC in distal tubules =less Na reab
- water remains in tubular fluid w Na -> excreted
45
diuretics: increased flow in tubules result
- to ENaC, ROMK in collecting duct
- reduction in ECF vol, increase release of aldosterone
- secretion of K through ROMK stimulated potentially leading to hypokalaemia
46
diuretics: prevent loss of K?
- thiazides diuretics often used in combo w K sparing agents that block ENaC and/or Na/K pump
- mineralocorticoid receptor antagonist prevent aldosterone promoting K secretion in collecting duct
- aldosterone is mineralocorticoid
47
nernst potential for K:
-94 mV
48
Em for cardiac mm cells:
-90 mV
