Week 1: Potassium homeostasis

Question 1

What is the function of the Na+ K+ ATPase?

Answer 1

3Na+ out and 2K+ into the cytoplasm
K+ generally higher in the cytoplasm so diffuses out down a conc gradient, cell membrane relatively permeable to k+ through open channels
Na+ higher in ECF but cell relatively impermeable to Na+ so no movement
This maintains the potential difference across the membrane (more negative inside) essential to function of excitable cells.

Question 2

What is the normal range of plasma potassium?

Answer 2

3.5 - 5.0 millimoles per Litre

Question 3

What is the normal regulated level of potassium in the ECF?

Answer 3

4.2 mmol per litre

Question 4

What is the distribution of potassium across the body stores?

Answer 4

98% in the ICF
2% in the ECF

Question 5

What are the average intakes of K+ into the human body?

Answer 5

About 50-200 mmol/L
Around 100 mmol per meal

Question 6

Why is it difficult to regulate K+ levels in the body?

Answer 6

Failure to rapidly remove potassium from blood stream after a meal results in hyperkalemia

Small decrease in potassium in the blood stream results in hypokalemia

Question 7

What are some consequences of hyperkalemia?

Answer 7

Cardiac arrhytmias
Cardiac arrest
Fibrillation

Question 8

What structure is mainly responsible for regulating K+ levels?

Answer 8

The kidney - match urine output (90-95% of K+ excretion) to input

Question 9

What is the role of cells in potassium regulation?

Answer 9

Contain 98% of K+ so can act as a source in hypokalemia or a store in hyperkalemia

Question 10

What happens to potassium when it is consumed in a meal in order to regulate its levels?

Answer 10

Rapidly transferred into cells to prevent hyperkalemia
Then excreted by the kidneys when approproate

Question 11

What is meant by internal K+ balance?

Answer 11

The regulation of K+ distribution between the ECF and the ICF.

Question 12

What factors are the mainplayers causing cells to intake Potassium ions?

Answer 12

Insulin
Catecholamines (adrenaline)

Question 13

How does insulin increase K+ absorption into the cell?

Answer 13

Insulin is released after a meal
Binds to IRS1 resulting in the activation of P13-K then PDPK1, this stimulates the GLUT4 transporter.
Also activates aPKC resulting in activation of the Na+/K+ ATPase
Causing K+ influx

Question 14

How do catecholamines increase K+ absoprtion into the cell?

Answer 14

Adrenaline binds to Beta 2 adrenergic receptors on skeletal muscle.
This activates cAMP then PKA.
This results in activation of the Na+/K+ pump resulting in K+ absoprtion

Question 15

What condition in relation to K+ levels are diabetics at risk of?

Answer 15

Hyperkalemia - unresponsive to insulin after a meal leading to decreased influx of K+ into cells

Question 16

What is the physiological role of aldosterone in regulating K+ levels?

Answer 16

Inc K+ intake causes secretion of aldosterone
Aldosterone causes K+ intake into cells and K+ excretion

Question 17

What conditions associated with aldosterone levels can have pathological K+ levels?

Answer 17

Conns syndrome - excess aldosterone leads to hypokalemia
Addisons disease - deficient aldoesterone leads to hyperkalemia

Question 18

How can acid base abnormalities affect K+ distribution?

Answer 18

Metabolic alkalosis - decreased ECF K+ concentration
Metabolic acidosis - increased ECF K+ concentration

Question 19

What factors increase K+ shift into cells?

Answer 19

Insulin
Catecholamines (adrenaline)
Aldosterone
Metabolic alkalosis

Question 20

What factors decrease K+ shift into cells? Hyperkalemia causing

Answer 20

Diabetes mellitus (untreated)
Addison disease
Beta-adrenergic blockers
Metabolic acidosis
Cell lysis

Question 21

How does the Na+ H+ exchanger affect the activity of the Na+ K+ ATPase?

Answer 21

Increased activity of Na+ H+exchanger results in H+ out and Na+ in.
This increases the activity of Na+ K+ ATPase
Leading to increased K+ influx into cells

Question 22

What is the difference between acidosis and acedmia?

Answer 22

Acidosis - increase in H+ conc
Acedmia - decrease in pH

Question 23

How does the Na+ HCO3- cotransporter effect the level of K+ in the ECF?

Answer 23

Increased activity of Na+ HCO3- leads to more Na+ and HCO3- in the cell.
INcrease activity of Na+ K+ pump to remove Na+
Leads to increased influx of K+ into ICF

Question 24

Describe how the activity of the chloride bicarbonate antiporter affect K+ influx into the ICF?

Answer 24

Increased activity of chloride bicarbonate antiporter results in more Cl- in ICF and more HCO3- in ECF
Increases activity of Cl- K+ symporter to remove Cl- from the ICF in doing so moves K+ from the ICF to the ECF

Question 25

What is the effect of cell lysis on ECF K+ levels?

Answer 25

Can result in hyperkalemia Large K+ stores are released from the cytoplasm as the cell is destroyed Common in severe muscle injury or red blood cell lysis

Question 26

How does strenuous exercise affect ECF K+ levels?

Answer 26

Can result in hyperkalemia (mild) Releases K+ from skeletal muscle (cause fatigue from impaired membrane excitability)

Question 27

What is osmolarity?

Answer 27

The concentration of solutes in a solvent

Question 28

How does an increase in ECF osmolarity affect K+ levels?

Answer 28

Increased ECF osmolarity (increased solutes and lower water potential) Water moves into ECF by osmosis from the cells This increases the conc K+ in cells, more likely to diffuse out increasing ECF K+ levels

Question 29

What three processes determine renal K+ excretion?

Answer 29

1. Rate of K+ filtration 2. Rate of K+ reabsorption 3. Rate of K+ secretion by the tubules

Question 30

How do you calcuate the ranel rate of K+ filtration?

Answer 30

Glomerular filtration rate x plasma K+ concentration

Question 31

What is the normal renal rate of K+ filtration?

Answer 31

756 mEq per day

Question 32

In the nephron where is K+ mainly reabsorbed or secreted?

Answer 32

Reabsorbed - 65% in PCT, 27% in Thick AL, 4% in collecting duct Secreted - 8% in collecting tubule and duct (and DCT) Overall 12% of K+ filtration is excreted in urine

Question 33

How does potassium excretion / reabsorption in the nephron vary dependent on the body needs?

Answer 33

Stable reabsorption in PCT and LOH Variation in excretion occurs due to changes in the amount secreted into the urine in the DCT, CT and CD.

Question 34

Describe how potassium is handled in the proximal tubule cell?

Answer 34

1. Active sodium reabsoprtion (SGLT2 and Na+k+ATPase) drives net fluid reabsorption from the lumen into the blood 2. K+ is reabsorbed paracellularly with H2O be solvent drag 3. Increased luminal voltage providing a stronger drive for K+ movement by paracellular diffusion 4. K+ uptake by the Na+K+ ATPase can exit the basolateral membrane by K+ channels or co-transport with Cl-, (small amount may go back into lumen by K+ channels)

Question 35

What is the handling of K+ like in the thick ascending limb cells?

Answer 35

1. Na+ K+ pump on basoloateral membrane creates conc gradient for NKCC2 2. NKCC2 (Na+ K+ and 2Cl-)from lumen into cytoplasm 3. K+ may enter lumen again by ROMPK channel down conc to ensure plenty supplied for NKCC2 4. ROMK creates a lumen positive voltage allows some K+ reaborption by paracellular diffusion 5. Alternativly K+ in the cytoplasm exts basolateral membrane by a voltage gated channel along with Cl-

Question 36

How is potassium secreted in the principle cells of the Late DCT and CT?

Answer 36

1. Na+ K+ ATPase - on basolateral membrane increases K+ in the cytoplasm 2. Creates a concentration gradient for K+ to diffuse out by BK and ROMK channels into renal lumen 3. The permeability of the membrane by these channels increases during high K+ intake 4. Na+ enters by ENaC channels on the luminal side to continue fuelling Na+K+ ATPase

Question 37

What are the different cell types with different roles in regards to K+ in the CT?

Answer 37

Principle cell - majority - secrete into lumen Intercalated cells - type A reabsorbed K and type B can secrete K+

Question 38

How do type A intercalated cells in the CT handle K+ reabsoprtion?

Answer 38

Active in severe hypokalaemia Action of principle cells decreases and intercalated cell activity increases CO2 diffuses from blood/ITF into cytoplasm, dissociates to HCO3- and H+ H+ leaves the lumen side by H+ K+ ATPase antiporter, increasing K+ cytoplasm concentration Then leaves the basolateral side by co transport with cli- maintained by cl- hco3- antiporter

Question 39

How do intercalated cells in the CT of nephron secrete K+?

Answer 39

Type B intercalated cells Activated in hyperkalemia CO2 diffuse in from blood and dissociates into H+ and HCO3- H+ K+ antiporter on basolateral membrane (H+ out into intersitial and soidum in to cytoplasm) Leaves cytoplasm down a conc gradient into renal lumen through K+ channels Co with. Cl- maintained by cl- hco3- antiporter

Question 40

What factors increase K+ secretion by principal cells in the CT/CD?

Answer 40

1. Hyperkalemia (ECF) 2. Increased tubular flow rate 3. Increased aldosterone These all affect the concentration gradient for K+ across the luminal membrane

Question 41

Descriibe how increased ECF K+ increases potassium secretion in the CD/CT?

Answer 41

More pronounced effect when ECF is above 4.2mmol?L K+ 1. Increases supply for Na+K+ ATPase on basolateral membrane leading to increase conc gradient for diffusion into the renal lumen 2. Increased conc in Interstitial fluid prevents backleakage from cytoplasm into ISF 3. Causes synthesis of BK and ROMK channels in luminal membrane 4. Stimulates aldosterone secretion

Question 42

How does a high tubular flow rate increase K+ secretion?

Answer 42

1.Rapidly clears lumen of high K+ conc filtrate - replaced by low conc - this maintains the conc gradient for K+ diffusion into lumen 2. Increases number of ROMK and BK channels in luminal membrane 3. Increases Na+ absorption so luminal voltage becomes more negative increasing K+ secretion

Question 43

How does aldosterone lead to increase K+ secretion in the collecting ducts?

Answer 43

1. Increases activity of Na+ K+ pump leading to increased cytoplasm concentration of K+ 2. Stimulates absorption of Na+ by ENaC channels, creating more negative luminal voltage encouraging K+ secretion 3. Increases the number of K+ channels on the luminal membrane

Question 44

What is the relationship between aldosterone and EC K+ conc?

Answer 44

Negative feedback mechanism High plasma K+ cause aldosterone production Aldosterone increases renal K+ secretion Decreases plasma K+, leads to decreased aldosterone production

Question 45

How does sodium intake affect K+ secretion when soidum levels are high?

Answer 45

1. High sodium and high renal perfusion decrease aldosterone release - decrease K+ secretion in CD 2. High Sodium - high BP - increased tubular flow rate - increased K+ secretion 3. Overall leads to unchanged K= secretion

Question 46

How does chronic vomitting effect K+ electrolyte levels?

Answer 46

Chronic vomiting - loss of electrolytes (particularly sodium = hypovolemia = RAAS activation = aldosterone release) leading to increased secretion of potassium

Question 47

How does diuretic use effect K+ levels?

Answer 47

Diuretics - increase GFR and tubular flow rate leading to increased K+ secretion Leads to hypokalemia

Question 48

How do potassium levels affect cardiac function?

Answer 48

Cause arryhtmias by direct effects of K+ and changing effects on Na+K+ pump and Na+/Ca2+ exhcnager

Question 49

How does hypokalemia cause cardiac complications?

Answer 49

QT prolongation and prominent U waves QT prolongation - due to slower rate of ventricular repolarisation Due to 1. Faster inactivation of K+ channels (to preserve K+ store) 2. Enhanced Na+ dependent inhibition (K+ channels are slower to open) 3. Downregulation of the expression of the K+ channel in acute maintained hypokalaemia

Question 50

How can hypokalemia lead to ventricular fibrillation?

Answer 50

1. Leads to delayed ventricular repolarisation 2. Increased membrane potential can cause inappropriate reactivation of L-type Voltage gasted Ca2+ ion channels in model cells, creates a secondary action potential in the repolarisation phase 3. Can cause abnormal re-excitation of ventricular myocytes resulting in ventricular fibrillation independent of the SAN

Question 51

Why does luminal voltage increase in the PCT?

Answer 51

Some K+ is passivly absorbed by solvent drag. K+ are secreted due to conc gradient established by Na+K+ATPase. More K+ secreted than reabsrobed in early PCT, combined with the voltage increases allowing more K+ to be reabsorbed later in the PCT by paracellular diffusion down an electrochemical gradient/