Potassium balance Flashcards
Potassium Intake
Why shouldn’t potassium intake be restricted? when should it be?
• A typical daily intake in the UK is 50-125mmol.
• Potassium is found particularly in leafy vegetables and most fruit and fruit juice, and in potatoes, especially if they are fried* or baked.
*high salt content
Unlike sodium, potassium intake should not be restricted routinely – only in cases of renal impairment with a low GFR. This is because potassium-containing foods include many healthy foods.
Potassium Homeostasis
Concentration of K inside the cell and outside the cell? rough estimates?
How is this difference maintained?
How is the internal balance maintained?
How is the external balance maintained? How can this go wrong?
WHat are the components of the intracellular and extracellular stores?
Internal K homeostasis in 70kg person:
The concentration of K is high within cells (~150mmol/L) and low outside of cells (~4.5mmol/L).
This difference is maintained by Na-K-ATPase.
Maintenance of this low ECF [K] is crucial.
From moment to moment the low ECF [K] is maintained mainly by internal balance, which shifts K+ between ECF & ICF compartments.
The major factors that affect this balance are insulin, aldosterone, pH and adrenaline.
External balance refers to the entire body & is the balance between what is taken in via the diet and what is excreted out.
In a healthy person external balance is maintained almost entirely by the kidney.
*increased losses due to intense heat (sweat) or diarrhoea/vomiting (i.e skin/GI)
‡with renal K balance can get both increased loss OR increased retention
Intracellular stores are muscle, liver, bone, RBC and other cells.
Extracellular stores are ECF and Plasma.
Importance of K+ homeostasis
two different forms of regulation? what do they regulate?
3 functions of potassium
What effect can changes in extraceullar conc of K+ have?
Regulation of K+ homeostasis implies:
• Acute regulation:
o Distribution of K+ through ICF and ECF compartments
• Chronic regulation:
o Achieved by the kidney adjusting K+ excretion & reabsorption
Potassium functions:
1. Determines ICF osmolality → cell volume
2. Determines resting membrane potential (RMP) → very important for normal functioning of excitable cells
o i.e. repolarisation of cell myocardial, skeletal muscle & nerve cells
3. Affects vascular resistance
However, although intracellular concentrations of the ions don’t change commonly, the extracellular concentration can and does change in certain clinical situations. These changes can change the resting membrane potential and have serious effects on the patient particularly on the cardiac muscle.
Na+-K+ ATPase Pump
What does this pump maintain?
where does the energy come from?
Why is a accumlation of Na+ outside of the cell beneficial?
Why is the gradient potential beneficial?
Relatively how much K+ intracellulary and extracellularly?
The pump in the membrane maintains high intracellular [K] & low [Na] along with many K+ and Cl- channels
A lot of these vital functions depend on the functioning of Na/K ATPase pump, which uses the energy from hydrolysis of ATP to do following:
It helps establish a net charge across the plasma membrane with the interior of the cell being negatively charged with respect to the exterior. This resting potential prepares nerve and muscle cells for the propagation of action potentials leading to nerve impulses and muscle contraction.
The accumulation of sodium ions outside of the cell draws water out of the cell and thus enables it to maintain osmotic balance (otherwise it would swell and burst from the inward diffusion of water).
The gradient of sodium ions is harnessed to provide the energy to run several types of indirect pumps.
> 90% body K located intracellularly and only 2.5% is found in ECF Na+-K+-ATPase pump maintains HIGH [K+]i and LOW [Na+]i
Internal Balance/Acute regulation
How does increase in ICF compartment come about?
what is the shift mainly subject to?
give the 4 different controls
What value is hyper and hypokalaemia? what value shouldn’t K+ rise above?
- ECF pool will change more dramatically with changes in body K distribution e.g. after a meal, get slight increase in plasma [K+], which is shifted into ICF compartment
- Shift mainly subject to hormonal control:
» Insulin
» Adrenaline
» Aldosterone
» pH changes
• VERY IMPORTANT that plasma [K+] does not rise beyond 6.5mmol.
- Hyperkalaemia = plasma [K+] > 5.5mM
- Hypokalaemia = plasma [K+] < 3.5mM
Resting Membrane Potential
What balance of ions determine RMP?
What can nernst equation be used to calculate?
Why is the actual value of RMP not the same as the calculated value?
Membrane potential formed by creation of ionic gradients (i.e. combination of chemical & electrical gradients)
Dynamic balance between membrane conductance to Na+ and K+ determines RMP normally
Nernst derived an equation that allows us to determine at what point the two forces (chemical and electrical gradients) balance each other - in other words, at what point we have an ionic equilibrium. Because the cell membrane is much more permeable to potassium than sodium at rest, the resting membrane potential is much closer to EK than it is to ENa.
The reason that the resting membrane potential and the EK are not identical is that the membrane is not completely permeable to potassium. One other ion that has substantial resting membrane permeability is Chloride.
Altering Potassium and RMP
What happens to Ek value with hyper and hypokalemia?
What can these changes in value severely affect? VERY DANGEROUS
Normal: [K]o=3.5mM and [K]i=140mM ⇒ EK = -98.5
Hyperkalemia: [K]o=7mM and [K]i=140mM ⇒ EK = -80
Hypokalemia: [K]o=1.5mM and [K]i=140mM ⇒ EK = -121.5
Can severely affect the heart - cardiac cell membrane potential (depolarisations and hyperpolarisations) producing characteristic changes in ECG.
[K+] & Action Potentials
low?
high?
Cell membrane hyperpolarization – increased negativity of voltage across membrane, hence decreased excitability of neurones & muscle cells (Low K+)
Cell membrane depolarization – decreased negativity of voltage, hence threshold approached quicker, increased excitability & muscle contractions (high K+)
ECG changes (examples don't need to learn)
Hypokalaemia: ↓amplitude T-wave, prolong Q-U interval, prolong P-wave
Hyperkalaemia: ↑QRS complex, ↑amplitude T-wave, eventual loss P-wave
Hypokalaemia
WHat is it caused by?
Give 4 examples of why this may come about?
consequences of hypokalaemia?
- Hypokalaemia caused by renal or extra-renal loss of K+ or by restricted intake e.g.
o Long-standing use of diuretics w/out KCl compensation
o Hyperaldosteronism/Conn’s Syndrome
-> INCREASED aldosterone secretion
o Prolonged vomiting Na+ loss - aldosterone secretion K+ excretion in kidneys
o Profuse diarrhoea (diarrhoea fluid contains 50mM K+)
Hypokalaemia results in ↓release of adrenaline, aldosterone & insulin
Hyperkalaemia
When is acute hyperkalemia normal?
4 disease states of hyperkalemia?
what value shouldn’t K+ rise above? Why?
How is insulin and glucose used in hyperkalemia?
Aldosterone and adrenaline use?
Effect on prolonged excercise on K+?
• Acute hyperkalaemia normal following prolonged exercise → normal kidneys excrete K+ easily
• Disease states:
o Insufficient renal excretion
o Increased release from damaged body cells e.g. during chemotherapy, long-lasting hunger, prolonged exercise or severe burns
o Long-term use of Potassium-sparing diuretics
o Addison’s disease (adrenal insufficiency)
• Plasma [K+] > 7mM life-threatening → asystolic cardiac arrest
• Insulin/Glucose infusion used to drive K+ back into cells
o Insulin extremely important – mechanism unclear, may stimulate Na-K-ATPase. Glucose is given with it to prevent hypoglycaemia
• Other hormones (aldosterone, adrenaline) stimulate Na+-K+ pump -> increased cellular K+ influx
During prolonged exercise, K is released from skeletal muscle into ECF. Rise in plasma K stimulates insulin – this enhances cellular K uptake returning plasma K towards normal – this is due to ability of insulin to stimulate activity of Na-K-ATPase pump. This shift inwards by K after admin of various drugs occurs very quickly i.e. 5-15mins after administration.
External Balance/Chronic Regulation
How is external balance maintained in a normal person?
Why is maintenance of noraml K+ in CVD important and a limit factor?
• In a healthy person, external balance is maintained almost entirely by the kidney
• Maintenance of normal K homeostasis increasingly important limiting factor in therapy of CVD
o Drugs like β-blockers, ACE inhibitors etc raise serum [K] →risk of hyperkalaemia
o Conversely loop diuretics, used to treat heart failure, enhance risk of hypokalaemia
• K+ excretion in the stools is not under regulatory control ⇒large amounts can be lost by extra-renal routes
Renal handling Na+ & K+
What are kidneys designed to do wth Na+ and K+? How is it filtered in GF?
• Human kidneys designed to conserve Na & excrete K
• Na+ & K+ filtered freely at glomeruli • Plasma & GF have same [Na+] & [K+] • In 24h, entire glomerular filtrate (~180 litres) contains: o 25 moles Na+ (=1.5 kg NaCl) o 0.7 moles K+ (= 50 g KCl) * *depends on dietary intake
Na+/K+ in the PCT
How much is reabsorbed? %
is it the same each time?
~60-70% Na+ and K+ reabsorbed in PCT
Fraction that is reabsorbed in PCT is ~ constant
Although absolute amount reabsorbed varies with GFR
K+ movement in PCT
Is it passive or an active process? Type of movement?
How does K+ move from lumen to ECF?
what happens to glucose and phosphate?
What happens to na+?
How does Na/K pump and k+ and cl- leaky channels come to play?
What inhibits Na/K pump? what happens if this pump is inhibited?
In PCT K+ reabsorption is passive & paracellular through tight junctions. Na+/K+ pump in cell membranes maintain HIGH intracellular [K+] and LOW intracellular Na. Also, many K & Cl channels through which ions leak out.
• By the end of the early proximal tubule essentially all the glucose, and much of the bicarbonate has been reabsorbed.
This establishes a Cl- & K+ conc. gradient from lumen to peritubular fluid and Na+ & K+ move passively along this gradient with Cl- in a paracellular route. Gradient for Na+ entry across the luminal membrane is maintained by the Na/K ATPase pump.
If this is inhibited (e.g. dopamine, digitalis) then the Na gradient is dissipated, eventually loose primary Na transport and the associated secondary active solute transport and also NO osmotic gradient for water transport.
