Electrolytes Flashcards
Describe the appearance of magnesium
Vial of clear colourless solution fo magnesium sulfate containing 2mmol/ml of ionic magnesium (50%)
How can magnesium be adminsitered
Orally, nebulised, IV
What salts can magnesium be prepared with?
Sulfate, chloride, hydroxide and aspartate
How does magnesium act in the heart?
It increased uptake of intracellular calcium into the sarcoplasmic reticulum leading to relaxation and a lower RMP stabilising the membrane, reducing spontaneous depolarisations and slowing rate in conducting tissue
What is magnesiums MOA
- Essential for the production of ATP, DNA, RNA and over 300 enzyme systems
- Dose dependent pre-synaptic inhibitino of ACh release at the NMJ leading to skeletal muscle relaxation
- It increased uptake of intracellular calcium into the sarcoplasmic reticulum leading to relaxation and a lower RMP stabilising the membrane, reducing spontaneous depolarisations and slowing rate in conducting tissue
- CNS depressant effects vai post synaptic inhibitino of NMDA receptors (non competitive)
- Cofactor in electrolyte homeostasis through its role in Na/K ATPase function
Effect of IV magnesium cardiovascularly
Peripherla vasodilation, bradycardia with slowed sinus node impulse formation, prolonged conduction time in AV node and through conductive tissue, prolonged refractory periods and attentuates vasoconstriction and arrhythmogenesis from adrenaline
What effect does magnesium have on the lung
Bronchodilator
Attenuates hypoxic pulmonary vasoconstriction
In toxic dopses causes respriatory failure
What effects does magnesium have outside the lung and heart
- CNS
CNS depressant - enhances other CNS depressant action
Anticonvulsant propoerties
High concentration inhibit catecholamine release from adrenergic nerve termianls
Prolongs NMB - Renal - vasodilation and diuretic
- Gut - osmotic laxative
- Obstetric - decreased uterine tone and contracitlity, increased placental perfusion
- Haem - prolongs clotting time and decreases thromboxane A2 synthesis inhibiting thrombin iinduced platelet aggregation
Magnesium affects the action of what other drugs
Neuromuscular blockade prolonged
Enhances the action of other sedatives
Magnesium half life IV
4 hours
Magnesium absorption orally
25-65% varying depending on systemic Mg levels
Magnesium protein binding
30%
Magnesium Vd
0.3L/kg
Magnesium excretion?
50% of exogenous magneisum load excreted in the urine even in deficiency
Reabsorption mainly via thick ascending limb and DCT
What is total body sodium content
50mmol/kg
* 60mmol/kg Na –> 70kg male has 4200mmol or 92g of which 70% is exchangeable and 50% of total body sodium is in ECF (5% in ICF), 45% in boneW
Where is sodium kept in the body? How much is accessable
- 60mmol/kg Na –> 70kg male has 4200mmol or 92g of which 70% is exchangeable and 50% of total body sodium is in ECF (5% in ICF), 45% in bone
What % of sodium content is in the ECF?
50%
What % of sodium content is in bone
45%
Is serum or plasma sodium higher?
- When plasma sodium is measured it is similar to intersitital fluid but by measuring it without plasma solids (protein) you remove the gibbs donnan effect (Na in total volume 140mmol/L, but in WATER volume is 147mmmol/L, while 140mmol in interstitial fluid and 12mmol/L in cells)
◦ Low in cells due to Na/K pump and low permeability - Can be measured using Na isotope
How does plasma sodium compare to intersitial fluid sodium
- When plasma sodium is measured it is similar to intersitital fluid but by measuring it without plasma solids (protein) you remove the gibbs donnan effect (Na in total volume 140mmol/L, but in WATER volume is 147mmmol/L, while 140mmol in interstitial fluid and 12mmol/L in cells)
◦ Low in cells due to Na/K pump and low permeability - Can be measured using Na isotope
What is the concentration of Na in cells?
12mmol/L
Daily intake of Na
50-100mmol/day
Absorption of sodium occurs via?
◦ Glucose-coupled - nutrient coupled absorption - especially in jejenum (AT2 upregulates)
◦ Na+/H+ exchange accounts for most of the intestinal absorption in the ileum (AT2 upregulates)
‣ H+ is then used to drive CL/HCO3 exchange to absorb chloride
◦ ENaC in the colon apical membrane - Aldosterone regulates colonic absorption to some minor extent`
How much sodium ends up in the stool per day?
- Total stool content 30 mmol/L, = only 3mmol/day is excreted in this way (i.e. almost 100% of dietary sodium is absorbed)
How is the extracellular vs intracellular sodium balance maintained?
- Cellular membranes have very poor sodium permeability and therefore no avenue to adjust extracellular sodium by movement in and out fo cells, only by elinination of Na and intake of H20
- Na+/K+ ATPase maintains high extracellular (135-145 mmol/L) and low intracellular concentration (10-15 mmol/L)
Where can sodium be sequestered
Sodium sequestration in skin and connective tissue
* Bound to negatively charged residues on glycosaminoglycans
* Not osomotically active
* Serves as a buffer to prevent haemodynamic changes from dietary sodium fluctuations
What is the main mechanism of sodium regulation?
Renal
Mainly distal nephron
What happens to sodium in the proximal neprhon
◦ Sodium is freely filtered
◦ 65% reabsorbed in PCT
‣ Driven by concentration gradient perpetuated by basolateral Na/K ATPase, with most of the Na reabsorbed by antiport with hydrogen and cotransport with glucose/amino acids
◦ None is reabsorbed in thin descending, and minimal in thin ascending
◦ 25% reabsorbed in thick ascending limb - furosemide sensitive NKCC2 cotransporter
What happens to sodium in the distal tubule?
◦ 5-10% by thiazide sensitive NCC cotransporter - load sensitive - reasborption increases when increased Na delivered
◦ 2% in collecting duct - passive and amiloride sensitive ENaC channel
What 5 factors specifically alter sodium reabsorption
◦ GFR manipulation by adrenaline/SNS input and Angiotensin 2 reduces GFR and reduces Na filtration and therefore potential loss
◦ Angiotensin II (increases reabsorption by increasing Na+/K+ ATPase activity in the proximal tubule, and increases NHE3 activity)
◦ Aldosterone (increases ENaC activation in the collecting duct and Na+/K+ ATPase activity in the thick ascending limb)
◦ Vasopressin (increases expression of ENaC in the collecting duct and NKCC2 in the thick ascending limb) - also regulating its concentration through water reabsorption
◦ Catecholamines by increasing NKCC2 expression in the thick ascending limb
What 4 reasons might sodium losses be increased in the ICU
- Sweat (in the unacclimatised, sweat contains up to 60mmol/L of sodium) with theoretical sweating of up to 12L per day (720mmol/day Na loss)
- NG drainage (erratic, 10-120 mmol/L)
- Ileostomy output (~120 mmol/L)
- Wound drain, pleural drain, burns (same as normal ECF, 135-145 mmol/L)
What is the plasma solids effect?
- Na in plasma 140 –> Na in interstitial fluid 140mmol/L
- Plasma water 93%, plasma solids 7% (proteins) –> Na content in plasma WATER is higher than interstitial fluid by 6-7mmol/L BUT if measured as though in the whole plasma the same
- i.e. measured concentration of Na is lower than actual plasma water concentration
- Then why if Na rises 6-7mmols/L does this only contribute 0.4mmols/L to oncotic pressure?
◦ Other electrolytes balance this out –> Cl concentration lower
◦ This means that the apparent protein concentration goes from 0.9mosm/L to 1.3mosmol/L
How much K is there in the body?
- 40mmol/kg of this 90% intracellulalr- extracelllularly is 2% and 8% in bone
◦ Intracellular concentration varies depending on cell type 120-150mmol/L, intravascular and intersitial 3.5-5 mmol/L equilibrating freely between these leaving 50-75mmol in extracellular fluid
Where is total body K distributed between?
- 40mmol/kg of this 90% intracellulalr- extracelllularly is 2% and 8% in bone
◦ Intracellular concentration varies depending on cell type 120-150mmol/L, intravascular and intersitial 3.5-5 mmol/L equilibrating freely between these leaving 50-75mmol in extracellular fluid
What is the intracellualr concentration of K
- 40mmol/kg of this 90% intracellulalr- extracelllularly is 2% and 8% in bone
◦ Intracellular concentration varies depending on cell type 120-150mmol/L, intravascular and intersitial 3.5-5 mmol/L equilibrating freely between these leaving 50-75mmol in extracellular fluid
How is K content measured?
- K content can be measured using K44 isotope which is of fixed proportion in the body - exchangeable K can be measured using radioactive K42 isotope
What is the role of K
- Maintenance of intracellular fluid tonicity / regulation of cell volume
- Maintenenance of resting membrane potential
◦ Responsible for the excitability of excitable tissues, action potentials etc - Structural function (incorporated into bone, ribosomes, DNA and RNA)
- Intracellular and extracellular messenger function (mediator of nociception, inflammation, vasodilation)
What is the daily intake of K? How is it absorbed?
- Intake is not regulated (passive paracellular gut absorption) - although 75mmol/L lost in faeces (of100ml). Passive paracellular diffusion via concentration gradient
◦ Daily intake 70mmol/day
How is K eliminated?
- Renal elimination is 95% of the total daily potassium excretion.
◦ 50-60% passively reabsorbed in proximal tubule, 30% reabsorbed in thick ascending tubule NKCC2 cotransporter and K is secreted in the distal tubular lumen
◦ Minimum urinary potassium is 5mmol/LK
How is potassium increased oral K regulated?
- Oral potassium intake
◦ Produces immediate kaliuresis; intestinal K+sensor is implicated - High potassium intake: leads to the increased expression of ROMK channels - takes time to develop
What happens to potassium with increased renal sodium delivery?
- High distal sodium delivery: compensatory increase in potassium secretion to maintain electroneutrality.
What is the effect of aldosterone on K
- Aldosterone
◦ Increases renal elimination by increasing the activity of ENaC channels in the nephron
◦ Increases GI elimination in colon (5% of total)◦ Aldosterone increases the activity of Na+/K+ ATPase pumps in skeletal muscle and its activity in the distal tubule/collecting duct promotes potassium excretion (it is released in response to hyperkalaemia)
What effect does plasma acid base have on potassium?
- Acid-base disturbances: metabolic acidosis causes distal potassium secretion to decrease with increased K/H exchange in intercalated cells
What effect does hydration have on potassium?
- hydration - systemic release of vasopressin, increasing ROMK channels on principal cels and NKCC2 transporter in thick ascending limb
How does insulin affect plasma K
◦ Insulin by the insertion of extra Na+/K+ ATPase pumps into the membrane, thus increased cellular potassium uptake
‣ Increases phosphorulation of insulin receptor substrate protein activating protein kinase C
How do catecholamine affect potassium
◦ Catecholamines increase the activity Na+/K+ ATPase pumps - specifically beta agonists (Beta 2)
Why does plasma pottasium rise more in some instances of Succinylcholnie use and not others?
◦ NMJ –> Nonspecific cation channels eg. acetylcholine-gated sodium channels in the neuromuscular junction are capable of leaking potassium out of the cell
‣ become more numerous in stroke, spinal injury, denervation so depolarisation muscle relaxants cause large rise in K
Why does K move in acid base?
◦ Acid-base changes effectively produce H+/K+ exchange across the membrane, i.e. metabolic acidosis produces a movement of potassium into the ECF
‣ Mediated by H+/Na exchanger in skeletal muscle decreasing activity in acidosis, resulting in reduced action of Na/K ATPase; and K leaky channels still present
What effect does energy availability have on potassium movement across cell membranes and therefore systemic K?
◦ ATP sensitive K channels - nucleotide sensitive cation channels in smooth muscle, cardiac muscle, skeletal muscle, pancreas
‣ Open in the absence of ATP, decreasing RMP –> K increased into extracellular fluid
‣ Closure promoted by high glucose, and opened by glucagon
‣ Nicorandil opens these channels, and sulfonylureas close them
What are the ECG changes of hyperkalaemia?
ECG changes of hyperkalemia: - Hyperexcitability initiailly with decreased RMP –> then reduced conduction velocity with inactivation of Na channels
* Tall peaked T waves with a narrow base
* Shortened QT interval
* ST-segment depression
* P wave widening/flattening, PR prolongation
* Sinus bradycardia, high-grade AV block
* Conduction blocks (bundle branch block, fascicular blocks)
* QRS widening with bizarre QRS morphology
How does rehydration affect plasma potassium?
- Rehydration (i.e. IV fluids)
◦ Dosing: 1000-2000ml
◦ Mechanism: dilution; support of diuresis
◦ Time to onset: minutes
◦ Duration of action: hours
How does bicarbonate affect plasma K
- Intracellular movement (temporary) Bicarbonate (esp. isotonic bicarbonate)
◦ Dosing: 100-200mmol
◦ Mechanism: H+/K+ exchange, using the Na+/K+ ATPase. Restores transmembrane gradient
◦ Time to onset: minutes
◦ Duration of action: 1-2hours
How do beta agonists affect plasma K
◦ Mechanism: increase the activity Na+/K+ ATPase pumps
◦ Dosing: 5mg nebulised salbutamol
◦ Time to onset: minutes
◦ Duration of action: hours
How does insulin affect plasma K
◦ Dosing: 10-50 units, administered with dextrose
◦ Mechanism: the insertion of extra Na+/K+ ATPase pumps into cell membranes, thus increased cellular potassium uptake
◦ Time to onset: seconds/minutes - max effect at 30 minutes
◦ Duration of action: 2-3 hours
◦ Removal via the urine
How does furosemide affect plasma K
◦ Mechanism: increased sodium delivery to the distal nephron; exchange of sodium for potassium, and thus kaliuresis
◦ Dosing: 40-80mg
◦ Time to onset: 20-40 minutes
◦ Duration of action: hours
How does resonium affect plasma K
◦ Cation exchange resin - resonium
◦ Mechanism: binding of potassium into the resin in exchange for another cation (eg. calcium or sodium) –> 1mmol of K for 1mmol of Na for every g of resin
◦ Dosing: 10-50g
◦ Time to onset: hours - oral slower than rectal as exchange in colon.
◦ Duration of action: hours
What is the baselien amount of magnesium in the body?
- 15mmol/kg in the body ~1000mmol in 70kg body
◦ 60% in bone
◦ 39% intracelluarly (10mmol/L) - bound to ATP, cell wall lipids (membrane stabiliser) and enzymes
◦ 1% extracellular. 10mmol total in ECF
‣ Intracellular magnesium enters cells freely and bound to ATP, cell wall lipids and enzymes
‣ Mangesium equilibrates freely between ECF
‣ 0.7-1mmol/L
Where is magnesium distributed in the body?
- 15mmol/kg in the body ~1000mmol in 70kg body
◦ 60% in bone
◦ 39% intracelluarly (10mmol/L) - bound to ATP, cell wall lipids (membrane stabiliser) and enzymes
◦ 1% extracellular. 10mmol total in ECF
‣ Intracellular magnesium enters cells freely and bound to ATP, cell wall lipids and enzymes
‣ Mangesium equilibrates freely between ECF
‣ 0.7-1mmol/L
What % of magnesium is extraceullar?
- 15mmol/kg in the body ~1000mmol in 70kg body
◦ 60% in bone
◦ 39% intracelluarly (10mmol/L) - bound to ATP, cell wall lipids (membrane stabiliser) and enzymes
◦ 1% extracellular. 10mmol total in ECF
‣ Intracellular magnesium enters cells freely and bound to ATP, cell wall lipids and enzymes
‣ Mangesium equilibrates freely between ECF
‣ 0.7-1mmol/L
In what state is serum magnesium?
◦ 40% protein bound
◦ 5-10% is complexed with phosphate lactate citrate, just like calcium
◦ 50-55% is available as free biologically active ion.
Describe the fate of dietary magnesium?
◦ 30% of dietary magnesium is absorbed in the intestine
◦ 90% passive concentration dependent paracellular absorption; 10% saturable active transport in jejenum/ileum
◦ More is absorbed in states of magnesium depletion
What is the response to 60mmol of KCL being given
Response to 60mmol of KCl – 60mmol of each. 60ml of water redistributed between all sites. Cl extracellular, K intracellular depending on preinfusion (in K excess more K from infusion remains outside cell proportionally 35%, vice versa down to 7%). K uptake intracellularly over minutes. If K spread evenly then 60mmol into 42L (Vd 70-70% of total body mass)
During infusion K leaves extracellular fluid up until it reaches a plateau of rate of ECF exit. Subsequently at infusion end K continues to be lost but more slowly into ICF. Worse by vol. than saline for ^Cl
Illustrate the change in potassium that occurs with administration
During infusion K leaves extracellular fluid up until it reaches a plateau of rate of ECF exit. Subsequently at infusion end K continues to be lost but more slowly into ICF.
