Potassium Balance Flashcards
What are the most prevalent cations in the body?
Na+ and K+ are the most prevalent cations in body fluids
What is the typical daily intake of potassium in the UK?
A typical daily intake in the UK is 50-125 mmol.
How should potasium in the diet be regulated?
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.
Describe the [K] in and around the cells of the body
[K] is high within cells and low outside of cells
What maintains the [K] gradient ?
Maintained by Na-K-ATPase
Maintenance of low ECF [K] is crucial
[K] is maintained mainly by internal balance, which shifts K+ between ECF & ICF compartments
What are the outputs of Potassium?
Urine‡: 45-112 mmols - ‡increased retention /loss
Stools: 5-10 mmols
Sweat: 5 mmols
What is the effect of diarrhoea/vomiting on potassium balance?
increased losses through stools and sweat due to intense heat or diarrhoea/vomiting (i.e skin/GI)
How do the kidneys control K balance via urine?
with renal K balance can get both increased loss OR increased retention
Describe acute regulation of K+ homeostasis
Distribution of K+ through ICF and ECF compartments
What is chronic regulation of K+ homeostasis?
Achieved by the kidney adjusting K+ excretion & reabsorption
What are the functions of potassium?
- Determines ICF osmolality → cell volume
- Determines resting membrane potential→v. important
for normal functioning of excitable cells
i.e. repolarisation of cell
⇒ myocardial, skeletal muscle & nerve cells
3.Affects vascular resistance
How does Na/K/ATPase pump maintain Na/K balance?
Pumps Na+ out of cell and K+ into cell driven by energy provided by ATP
What is the role of the Na/K/ATPase pump?
Na+-K+-ATPase pump maintains HIGH [K+]i and LOW [Na+]i
What is the effec of changing the distribution of K within the body?
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
What causes shifts in K distribution around the body?
Shift mainly subject to hormonal control: Insulin Adrenaline Aldosterone pH changes
What is the maximum healthy level of [K+]?
VERY IMPORTANT that plasma [K+] does not rise beyond 6.5 mmol
What is hyperkalaemia?
Hyperkalaemia = plasma [K+] > 5.5mM
What is hypokalaemia?
Hypokalaemia = plasma [K+] < 3.5mM
How is the membrane potential formed?
Membrane potential formed by creation of ionic gradients (i.e. combination of chemical & electrical gradients)
What determines the resting membrane potential ?
Dynamic balance between membrane conductance to Na+ and K+ determines RMP normally
What are the consequences of developing hyper/hypo-kalaemia?
Can severely affect the heart - cardiac cell membrane potential (depolarisations / hyperporlarisations) producing characteristic changes in ECG
What is cell membrane hyperpolarisation?
increased negativity of voltage across membrane, hence decreased excitability of neurones & muscle cells
What is cell membrane depolarisation?
Decreased negativity of voltage, hence threshold approached quicker, increased excitability & muscle contractions
Describe what you would see on an ECG of a hyperkalemic patient
↑QRS complex, ↑amplitude T-wave, eventual loss P-wave
Describe the ECG pattern oh a hypokalaemic patient
↓amplitude T-wave, prolong Q-U interval, prolong P-wave
What causes Hypokalaemia?
caused by renal or extra-renal loss of K+ or by restricted intake
What factors contribute to hypokalaemia?
- Long-standing use of diuretics w/out KCl compensation
- Hyperaldosteronism/Conn’s Syndrome
(↑↑ aldosterone secretion) - Prolonged vomiting → Na+ loss → ↑aldosterone secretion
→ K+ excretion in kidneys - Profuse diarrhoea (diarrhoea fluid contains 50mM K+)
What effect does Hypokalaemia have on hormones?
Hypokalaemia results in ↓release of adrenaline, aldosterone & insulin
Why is it possible to get hyperkalaemia if not in disease state?
Acute hyperkalaemia normal following prolonged exercise → normal kidneys excrete K+ easily
When does hyperkalemia become a disease state?
- Insufficient renal excretion
- Increased release from damaged body cells eg. during chemotherapy, long-lasting hunger, prolonged exercise or severe burns
- Long-term K+ sparing diuretics use
- Addison’s disease (adrenal insufficiency)
How can hyperkalaemia lead to cardiac arrest?
Plasma [K+] > 7mM life-threatening → asystolic cardiac arrest
How can we treat hyperkalaemia?
Insulin/Glucose infusion used to drive K+ back into cells Insulin extremely important – mechanism unclear, may stimulate Na-K-ATPase Other hormones (aldosterone, adrenaline) stimulate Na+-K+ pump ⇒ ↑cellular K+ influx
How i sthe external balane of K+ maintained?
In a healthy person, external balance is maintained almost entirely by the kidney
Which drugs put you at risk of hyperkalaemia?
Drugs like β-blockers, ACE inhibitors etc raise serum [K] →risk of hyperkalaemia
What drugs have the risk of developing hypokalemia?
Conversely loop diuretics, used to treat heart failure, enhance risk of hypokalaemia
How do kidneys maintain a K+ balance?
Human kidneys designed to conserve Na & excrete K
Na+ & K+ filtered freely at glomeruli
So Plasma & GF have same [Na+] & [K+]
How much of the Na+/K+ is reabsorbed in PCT?
Fraction that is reabsorbed in PCT is ~ constant at 60-70%
Although absolute amount reabsorbed varies with GFR
How does K+ reabsorption occur in PCT?
In PCT K+ reabsorption is passive & paracellular through tight junctions.
Describe the balance of ions maintained by the Na/K/ATPase pump
Na+/K+ pump in cell membranes maintain HIGH intracellular [K+] and LOW intracellular Na however - many K & Cl channels which ions leak out through
By the end of the PCT, what has been reabsorbed?
By the end of the early proximal tubule essentially all glucose, aa and much of the bicarbonate has been reabsorbed
How does reabsorption of substances allow K+ balance?
Establishes a Cl- & K+ conc. gradient from lumen to peritubular fluid
Na+ & K+ move passively along gradient with Cl- in a paracellular route
Gradient for Na+ entry across luminal membrane maintained by Na/K ATPase pump
What is teh consequence of inhibiting the Cl- & K+ gradient?
Na gradient is dissipated, eventually loose primary Na transport and the associated secondary active solute transport and also NO osmotic gradient for water transport
How is an osmotic gradient created in the LoH?
LoH creates a cortico-medullary osmotic conc. gradient in medulla,
descending limb = very permeable to water but ascending limb aren’t
Why is the fluid more concentrated at the tip of the LoH?
Fluid enters descending limb
water moves out
Fluid gets more concentrated reaching 1200 mOsm at tip of LoH
How do Na and Cl move out of the ascending limb?
Ascending limb is highly permeable to solutes so Na & Cl diffuse out
How do Na and Cl move out of the thick ascending limb?
Active reabsorption/pumping of Na & Cl out of fluid, => more dilute
Via Na/2Cl/K symporter on luminal membrane
driven by the [Na] gradient from lumen-cell
What is the fate of the solutes in the surrounding tubular cells?
Entry of Na from Na-H antiporter
Na/K ATPase pump on basolateral side and co-transport of Cl & K out of cell (especially in the thick ascending limb).
Some diffusion of K back into descending limb
What are the 2 ways K+ is processed in the DCT?
- > 90% of filtered K reabsorbed in PCT & LoH
- Excretion of K into urine by overload,
controlled by secretion in principal cells of
late DCT & CD
Explain how K+ is excreted due to the chemical gradient
- Excess K enters secreting cells from blood via Na-K-
ATPase pump - Diffuses down electrochemical gradient through K
channels in luminal/apical membrane→ tubular fluid - Electrical gradient across luminal membrane normally
opposes K efflux from cell BUT gradient is reduced by
Na flux through EnaC channel in membrane -
aldosterone sensitive - Chemical gradient dominates
How does the amount of Na+ reabsorbed affect K+ secretion?
The more Na+ reabsorbed by the principle cell, the more K+ secreted
What is K+ excretion into urine via the DCT determined by?
Increased K+ intake
Changes in blood pH
How does alkalosis affect the k secretion?
Alkalosis ⇒ ↑excretion of K+ ⇒ ↓serum [K+]
What is the effect of acute acidosis on K secretion ?
Acute Acidosis ⇒ ↓excretion of K+ ⇒ ↑serum [K+]
How is acute acidosis caused?
Achieved by:
- activity of Na-K-ATPase pump
- electrochemical gradient
- permeability of luminal membrane channel
How does aldosterone affect the Na/K/ATPase pump?
↑activity of Na+/K+ pump ⇒ ↑K+ influx ⇒ ↑[K+]i ⇒ cell-lumen concentration gradient
What aeffect does aldosterone have on the ENaC channel?
↑ENaC channels ⇒ ↑Na+ reabsorption ⇒ ↓cell negativity and ↑lumen negativity ⇒ voltage gradient
Redistributes ENaC from intracellular localization to membrane
Explain the effect of aldosterone on K permeability of luminal membrane
Causes ↑permeability of luminal membrane to K+
How does increased plasma [K] increase K secretion into urine?
slows exit from basolateral membrane ⇒ ↑[K+]i ⇒ cell-lumen concentration gradient
↑activity of Na+/K+ ATPase ⇒ ↑[K+] within cell
↑Plasma [K] ⇒ stimulates aldosterone secretion
What increases the tubule flow rate of fluid?
resulting from ↑GFR or inhibition of reabsorption upstream or diuretics (K+ wasting diuretics)
What is the purpose of increasing the tubule fluid flow rate?
Sweeps away secreted K, making the tubular fluid [K] low allowing more rapid rate of net secretion & maintains [K+] gradient favourable to secretion
How does ADH effect K secretion?
stimulates K secretion by increasing the K conductance of the luminal membrane
- Effect not as great as that of aldosterone
Where does K reabsorption take place?
Occurs mainly in Intercalated cells (late DCT & CD)
under normal conditions most reabsorption occurs in PCT & LoH
Explain why reabsorption of K occurs in disease states
The DCT, connecting tubule and the cortical CD don’t secrete K+ - may even reabsorb K+
The K+ which passes through cortical CD is reabsorbed in the medullary CD and K+ excreted in urine is minimal
What disease states cause K reabsorption?
In people on a low K+ diet, or suffering from K+ loss e.g. diarrhea
Explain how the RAAS system responds to low BP and/or vomiting
- JGA detects ↓BP
Mac Den detects ↓[Na] in DCT - Renin released from renin-containing JGA
cells - Indirectly forms Angiotensin II causing
vasoconstriction and stimulation of adrenal
cortex to produce aldosterone - Aldosterone ↑Na reabsorption in DCT, by
insertion of more Na/K-ATPase pumps and
ENaC channels - Na+ brings water in via osmosis, restoring
fluid volume and pressure. - More K+(or H+) secreted in exchange ∴
aldosterone increases recovery of Na and
loss of K+(or H+)
This is important because a high plasma [K+] itself causes release of aldosterone from adrenal cortex.
What inhibits the effects of Aldosterone ?
Renin release is suppressed by direct negative feedback from Angiotensin II
How does aldosterone affect pH of body?
Aldosterone acts on intercalated cells to ↑ activity of Na+, H+ antiporter - influences acid-base status of body by increasing H+ secretion – ↑serum pH
Which factors cause K+ influx into cells?
Insulin
Aldosterone
Alkalosis
β-adrenergic stimulation
Which factors cause an efflux of K+ out of cells into ECF?
Diabetes Mellitus (Insulin deficiency) Addison's Disease (Aldosterone deficiency) Acidosis Cell lysis β-adrenergic blockade Strenuous exercise Increased ECF osmolarity
