Electrolytes

Question 1

What does the sodium potassium pump do?

Answer 1

3 Na+ out of cell and 2 K+ into cell

Question 2

What is the ECF concentration of potassium?

Answer 2

s normally at 4.2mmol/L, ranges from 3.5-5

Question 3

What regulates potassium under normal conditions?

Answer 3

• Insulin - postprandial release of insulin also shifts dietary K+ into cells until the kidney excretes the K+ load
• Catecholamines

Question 4

What factors affect potassium distribution?

Answer 4

Question 5

What is conn’s syndrome?

Answer 5

excess aldosterone secretion is associated with hypokalaemia due to movement of extracellular K+ into cells

Question 6

What are acid-base transport pathways?

Answer 6

A- Na+-H+ exchange - Na+ that enters by this route must be removed by the Na+/K+-ATPase =

• K+ uptake will be greater when Na+-H+ exchange activity is stimulated
• K+ uptake will be diminished when the rate of Na+-H+ exchange is reduced

B- e.g. in Acidosis with acidemia

• decrease in extracellular
  HC03
• = inhibition of the inward rate of Na+-HCO3 cotransport
• = fall in intracellular Na+ and reduced Na+/K+ATPase activity

C- e.g. Acidosis with acidemia

• CI-HCO3 exchange also may contribute to apparent K+-H+ exchange
• = decrease in extracellular HCO3 = increase the inward movement of CI- by CH- HCO3 exchange = rise in intracellular CI-= K+ efflux by K+-CI- cotransport

Question 7

What is renal potassium excretion determined by?

Answer 7

1. the rate of K+ filtration (= glomerular filtration rate x plasma K+ concentration). The normal rate of K+ filtration by the glomerular capillaries is about 756 mEq/day. E.g. 180 L/day (GFR) × 4.2 mEg/L (plasma K+ concentration)
2. the rate of K+ reabsorption by the tubules
3. the rate of K+ secretion by the tubules

Question 8

What is the tubular handling of potassium under normal conditions?

Answer 8

Question 9

What is the role of intercalated cells?

Answer 9

Question 10

What are the factors the regulate potassium secretion?

Answer 10

• increased ECF potassium concentration
• increased tubular flow rate
• increased aldosterone

Question 11

How does increased ECF potassium concentration regulate potassium secretion?

Answer 11

Increased dietary K+ intake and increased ECF K+ concentration stimulate K+ secretion by 4 mechanisms:

• Increased ECF K+ concentration stimulates the Na+/ K+ ATPase pump = increasing K+ uptake across the basolateral membrane. This increased K+ uptake increases intracellular K+ concentration -> K+ to diffuse across the luminal membrane into the tubule
• Increased extracellular K+ concentration increases the K+ gradient from the renal interstitial fluid to the interior of the epithelial cell. Reduces backleakage of K+ ions from inside the cells through the basolateral membrane
• Increased K+ intake stimulates synthesis of K+ channels and their translocation from the cytosol to the luminal membrane -> increases the ease of K+ diffusion through the membrane
• Increased K+ concentration stimulates aldosterone secretion by the adrenal cortex -> further stimulates K+ secretion

Question 12

How does increased tubular rate regulate potassium secretion?

Answer 12

There are 2 effects of high-volume rate that increase K+ secretion:

• When K+ is secreted into the tubular fluid - the luminal concentration of K+ increases = reducing the driving force for K+ diffusion across the luminal membrane. With increased tubular flow rate = the secreted K+ is continuously flushed down the tubule. The rise in tubular K+ concentration becomes minimised and net K+ secretion is increased
• A high tubular flow rate also increases the number of high conductance BK channels in the luminal membrane -> increasing conductance of K+ across the luminal membrane

Question 13

How does increased aldosterone regulate potassium secretion?

Answer 13

• increases intracellular K+ concentration by stimulating the activity of the Nat/K+-ATPase in the basolateral membrane
• stimulates Na+ reabsortion across the luminal membrane = increases the electronegativity of the lumen = increasing the electrical gradient favoring K+ secretion
• increases the number of K+ channels in the luminal membrane and therefore its permeability for K+

Question 14

What are the effects of high sodium?

Answer 14

Question 15

What are the electrolyte levels associated with purging?

Answer 15

Question 16

What happens in hypokalemia?

Answer 16

• The hypokalaemia observed in purging individuals is not a direct consequence of K+ loss from vomiting but due to its effect on triggering the activation of the RAAS in response to blood volume depletion
• Increase aldosterone secretion = increases K+ excretion through increasing expression K+ channels and Na+/K+ ATPase in the principal cells of the collecting duct = increased urinary K+ losses
• QT prolongation is seen in patients with bulimia nervosa. QT prolongation is due to a slower rate of repolarisation of ventricular myocytes. Hypokalaemia is thought to inhibit the conductance of the slow delayed-rectifier voltage-gated K+ channel that is responsible for speeding up the repolarisation of the ventricular myocytes There are a number of suggested mechanisms for this including:
• faster inactivation
• enhanced Na+-dependent inhibition
• downregulation of the expression of the K+ channel in acute-maintained hypokalaemia

Question 17

Glomerular filtration rate (GFR)=

Answer 17

Kf is the filtration coefficient (how permeable the capillary is to water). This is high in glomerular capillaries as they need to be very leaky to do their
job.

σ (sigma) is the reflection coefficient (how permeable the capillary is to protein). This can change if the patient loses the negative charge of the basement membrane (eg in nephrotic syndrome)

P= hydrostatic pressure
Pi= oncotic pressure

Question 18

Flow=

Answer 18

change in pressure/resistance of arterioles

Question 19

Afferent vs efferent arteriolar constriction effect of GFR

Answer 19

Puf= Pressure of urine filtration

Question 20

How does the sympathetic nervous system affect renal blood flow?

Answer 20

Question 21

How does angiotensin II affect renal blood flow?

Answer 21

Question 22

How does atrial and brain natriuretic peptide (ANP and BNP) affect renal blood flow?

Answer 22

Question 23

How does prostaglandins affect renal blood flow?

Answer 23

Question 24

How does dopamine affect renal blood flow?

Answer 24

Shifts blood flow from skin and muscle to vital organs, can be used to treat haemorrhage

Question 25

How does nitric oxide affect renal blood flow?

Answer 25

Question 26

Vasoconstrictors vs vasodilators in regulation of renal blood flow

Answer 26

Question 27

What are the 2 mechanisms that auto regulate renal blood flow and GFR?

Answer 27

1. **Myogenic –** afferent arteriole responds to changes in blood flow due to changes in pressure (stretch) 2. **Tubuloglomerular feedback –** afferent (and efferent) arteriole responds to changes in tubular flow

Question 28

What is the myogenic response?

Answer 28

Question 29

What is tubuloglomerular feedback?

Answer 29

Question 30

When can autoregulation be overridden?

Answer 30

Autoregulation can be overridden in certain circumstances (eg following haemorrhage you want GFR to decrease so you can hang on to more water to restore blood volume) by the renal sympathetic nerve

Question 31

Filtered load=

Answer 31

the amount of a substance filtered into Bowman’s space per unit time. = GFR X P[x] (plasma concentration of substance)

Question 32

What is Na+ balance? What happens if it is unbalanced?

Answer 32

Na+ excretion exactly equals Na+ intake • If Na+ excretion is less than Na + intake, then the person is in positive Na+ balance → ECF volume expansion → increased PB → Oedema • If Na+ excretion is greater than Na+ intake, then a person is in negative Na+ balance → ECF volume contraction → decreased PB

Question 33

How is Na+ gained and lost?

Answer 33

Na+ gain • Food • Average diet contains far more Na+ than needed • 1.5 – 2.3 g/day vs ~8 g/day • Low Na+ diet triggers salt cravings Na+ loss • Small amount in faeces • Small amount in sweat (unless prolonged and profuse) • Urinary excretion balances the amount ingested • 100% of filtered load can be reabsorbed when Na+ intake is limited

Question 34

Where is Na+ reabsorbed across the nephron?

Answer 34

Question 35

What is effective arterial blood volume EABV?

Answer 35

is that portion of the ECF volume contained in the arteries and is the volume “effectively” perfusing the tissues. Changes in ECF volume lead to changes in EABV in the same direction. Oedema is an exception- the increase in ECF volume is associated with a decrease in EABV (due to excessive filtration of fluid out of the capillaries into the interstitial fluid)

Question 36

What is ANP secreted by?

Answer 36

ANP is secreted by the atria in response to an increase in ECF volume. urodilatin, which is secreted by the kidney, and brain natriuretic peptide (BNP), which is secreted by cardiac ventricular cells and the brain have the same effect as ANP

Question 37

Response to increased vs decreased Na+ intake?

Answer 37

Question 38

How is phosphate distributed around the body?

Answer 38

• Localised primarily in bone matrix (85%) • The rest is in ICF (15%) and ECF (<0.5%) • In ICF, phosphate is a component of nucleotides (DNA and RNA), high-energy molecules (e.g., ATP), and metabolic intermediates. • In ECF, phosphate is present in its inorganic form and serves as a buffer for H+ . • 10% of the phosphate in plasma is protein bound

Question 39

How is phosphate renally handled?

Answer 39

Question 40

How is calcium distributed around the body?

Answer 40

• Most of the body’s calcium (Ca2+) is contained in bone (99%) • The remaining 1% is present in ICF (mostly in bound form) and in ECF • The total Ca2+ concentration in plasma is 5 mEq/L or 10 mg/dL. • Of the total plasma Ca2+ , 40% is bound to plasma proteins, 10% is bound to other anions such as phosphate and citrate, and 50% is in the free, ionised form. • The plasma Ca2+ concentration is regulated by PTH

Question 41

How is calcium renally handled?

Answer 41

Question 42

How is magnesium renally handled?

Answer 42

Question 43

What is the timeline of the response to a haemorrhage?

Answer 43