Electrolytes/Acid-Base Flashcards
How does acid base affect iCa level?
Acidic pH facilitate dissociation of calcium from protein and increases the amount of iCa in the sample.
Alkaline pH favors calcium binding to protein, thus decreasing the amount of iCa
Which ion is the main intracellular anion?
Phosphate
Where is the central osmocenter?
Hypothalamus
What are the two stimuli for ADH release?
1) Increased plasma osmolarity
2) Decreased effective circulating volume (signals sent by baroreceptors)
- maintenance of effective circulating volume is always prioritized over maintenance of normal plasma osmolality
What is ADH also called?
Arginine vasopressin
Explain how ADH increased renal distal tubules and collection duct water resorption.
ADH binds to V2 receptors, which are coupled with stimulatory G proteins (Gs) → activates adenylate cyclase (AC) → stimulates formation of cyclic adenosine monophosphate (cAMP) from ATP → activates protein kinase A and phosphorylation of intracellular proteins → moving aquaporin-2 (AQP-2) to the luminal side of the cell membrane.
On the basolateral side of the cell membrane are other aquaporins, AQP-3 and AQP-4, that permit water to flow out of the cell, although these aquaporins do not appear to be regulated by AVP.
Where do most and second most Na absorption happen in the nephron? What channels do they use?
1) Proximal renal tubule (about 67%)
- Co-transport with glucose, AA, phosphate, Na-H antitransporter
2) Ascending loop of Henles (about 25%)
- Na-K-2Cl cotransporter, Na-H antitransporter
3) Distal convoluted tubule (about 5%)
- Na-Cl cotransporter
4) Collecting duct (about 3%)
- Na channel
What stimulate aldosterone and what inhibit it?
Stimulation: Angiotensin II, Hyperkalemia, ACTH
Inhibition: Dopamine, ANP
True or False: catecholamine can stimulate proximal renal tubule Na reabsorption through 𝜶1 receptor.
True
True or False: catecholamine can stimulate renin release through 𝜶1 receptor.
False
𝜷1
True or False: Angiotensin II can stimulate Na-H antiporter in the proximal tubules and facilitate Na reabsorption.
True
List 5 drugs that can stimulate ADH release.
1) Barbiturates
2) Angiotensin II
3) Beta adrenergic drugs
4) Narcotics
5) Vincristine
6) Tricyclic antidepressant
7) Cholinergic drugs
8) Carbamazepine
What are the three big categories of causes for hypernatremia. List 3 examples for each categories.
1) Pure water deficit
- Diabetes insipidus (central/nephrogenic)
- Primary hypodipsia
- No access to water
- High environmental temperature
2) Hypotonic fluid loss
- Extra-renal: GI loss (V/D), third-space loss, burn
- Renal: AKI, CKD, post-obstructive diuresis, diuretic administration
3) Impermanent solute gain
- Salt toxicity
- Hyperaldosteronism
- Hypertonic saline infusion
What is the cause of central diabetes insipidus?
Partial or lack of production of ADH (congenital, trauma, neoplasia, idiopathic)
For dogs with central DI, administration of DDAVP can improve the USG and/or osmolarity, but the initial effect may not be very significant. Why?
Because of renal medullary wash out → no concentration gradient for water to move
What is the MOA of glucocorticoid, E. coli endotoxemia, hypokalemia, hypercalcemia causing NDI?
Inhibit adenyl cyclase on the basal membrane → inhibit aquaporin 2 movement to the luminal membrane → decrease water reabsorption
- Other causes of NDI: hepatic insufficiency, hyperthyroidism, medullary interstitial amyloidosis (e.g. cats, Sharpei), pyelonephritis, polycystic kidney disease
How does thiazide help with DI management?
Thiazide cause mild volume depletion → increase water and Na reabsorption at the proximal renal tubule and decrease the flow to the distal collecting tubule where water is impermeable → decrease urine volume
How does paintballs cause hypernatremia?
They usually contain polyethylene glycol, glycerol and sorbitol, which can cause severe osmotic diarrhea
When we correct the chronic hypernatremia or hyponatremia, what is the rate that we shouldn’t exceed?
not exceed 10-12 mEq/L per 24 hours
What can cause hyponatremia with high osmolarity?
Hyperglycemia, mannitol infusion
What can cause hyponatremia with normal osmolarity (pseudohyponatremia)?
Hyperlipidemia
Severe hyperproteinemia
How to calculate osmol gap?
Osmol gap = Measured osmolarity - Calculated osmolarity
What is normal osmol gap in dogs and cats?
< 10 mOsm/L
What are the common cause of increased osmol gap?
Ethylene glycol intoxication, ethanol intoxication
List three differentials for hyponatremic patients that are hypervolemic, euvolemic or hypovolemia.
1) Hypervolemic
- CHF
- Advanced CKD
- Cirrhosis
- Nephrotic syndrome
2) Euvolemic
- Psychogenic polydipsia
- SIADH
- Anti-diuretic administration
- Hypotonic fluid
- Myxedema coma
3) Hypovolemic
- Renal: diuretic administration, hypoadrenocorticism
- Non-renal: GI loss, third space loss (guess they can do whatever they want)
Why do some dogs with chronic third space loss develop pseudo-Addison’s?
1) Volume depletion cause vasopressin release → increase water reabsorption → hyponatremia
2) Volume depletion cause decrease renal potassium excretion → hyperkalemia
What are the diagnostic criteria for syndrome of inappropriate ADH release (SIADH)?
- Hyponatremia with hypoosmolarity
- Abnormally high urine osmolarity in the presence of plasma hypoosmolarity
- In psychogenic polydipsia, urine osmolarity will be very low
- Normal renal, adrenal and thyroid function
- No evidence of hypovolemia or hypervolemia (or third space loss)
- Presence of natriuresis despite hyponatremia and plasma hypoosmolarity as a result of mild volume expansion (urine Na concentration usually > 20 mEq/L)
What happens to the brain if hyponatremia is corrected to quickly?
Osmotic demyelination
How does hyperadrenorcorticism cause PUPD?
Excessive glucocorticoid decrease ADH secretion from the posterior hypothalamus
How does hypercalcemia cause PUPD (5 causes)?
1) Affect adenyl cyclase so ADH cannot activate the cascade
2) Increased medullary blood flow
3) Impaired NaCl transport to the loop of Henle
4) Direct stimulation of thirst center
5) Hypercalcemic nephropathy
How does severe liver disease cause PUPD (3 causes)?
1) Decrease BUN → decrease medullary solute
2) Decrease metabolism of endogenous hormones (e.g. cortisol, aldosterone)
3) Hypokalemia
How does Addison’s disease cause PUPD?
Renal Na loss with medullary solute washout
What are the idiogenic osmoles made from?
inositol, glutamine, glutamate
How long does it take for the idiogenic osmoles formation in the brain to fully compensate the hypernatremia?
2-7 days
What is the recommended percentage of Na raise in the first day for the patient with symptomatic hyponatremia?
no more than 10-15% in the first day
What is the formula to calculate sodium deficit?
Sodium deficit (mEq) = (Target Na - Patient Na) x 0.6 x body weight
During the treatment of correcting hyponatremia, correcting potassium is also an important part of the therapy if the patient is hypokalemic. Why?
After giving the potassium, the potassium will enter the cell and exchange Na in order to reach electroneutrality.
- It will also allow Na-K ATPase to function normally? Maybe?
What is the limit rate for Na correction
No more than 10 mEq/L in the first 24 hours and no more than 18 mEq/L in the first 48 hours
What is the stabilization therapy for acute hypernatremia with clinical signs?
Give D5W at the rate of 7-10 ml/kg/hr to correct the Na at the rate of 2-3 mEq/kg/hr for the initial 2-3 hours or until neurological signs resolve.
What is the stabilization therapy for acute hyponatremia with clinical signs
Give 3% HTS at the rate of 1-2 ml/kg over 10-20 min to raise Na by 4-6 mEq/L
Which electrolyte is the major determent of the resting membrane potential?
Potassium!
More precisely, the ratio of intracellular K to extracellular K
Which electrolyte has higher permeability to the cell membrane, Na or K?
K (100x more permeable than Na)
What is normal resting membrane potential?
-90 mV
How does hyperkalemia affect the resting membrane potential?
It decreases the resting membrane potential (make it less negative) and make the cell membrane more excitable, but if the new resting membrane potential becomes less than the threshold potential, the cell will depolarize but cannot repolarize → no longer excitable
Draw how does potassium and calcium affecting the resting membrane potential and threshold.
How does hypocalcemia affect the threshold potential?
It increases the threshold potential (make it more negative) and make the cell more excitable.
Does acidemia increase or decrease membrane excitability?
Decrease
True or False: Aldosterone can affect colonic potassium absorption.
True
What is the MOA of using terbutaline to treat hyperkalemia?
Terbutaline is an 𝜷2 agonist. It will activate the Na-K ATPase on the cell membrane (especially muscles and liver) and increase K uptake by the cell.
How does acid base affect the potassium movement across the cell membrane?
Acidosis → K moves to ECF (in exchange of H+)
Alkalosis → K moves to ICF
- Metabolic acid-base derangement will cause more significant change of K than respiratory.
How many percentage of K is reabsorbed at proximal renal tubule and ascending loop of Henle’s respectively?
70% and 10-20%
In the proximal part of the renal tubule, is K transported mainly via transcellular route or paracellular route?
Paracellular route
Which part of the nephron/cells is responsible for K secretion?
Principle cells at the Connecting tubule and collecting duct
There are two form of intercalated cells at the kidney collecting duct - 𝜶 and 𝜷. What are their functions?
𝜶 intercalated cells - secrete acid
𝜷 intercalated cells - secrete bicarb
How does aldosterone affect the potassium secretion in the distal renal tubules
1) It stimulates ENaC at the principle cells and increases Na reabsorption → increases Na-K ATPase activity at the basal membrane → facilitates K secretion
2) Directly increase K channel at the luminal membrane
How does aldosterone affect the hydrogen secretion in the distal renal tubules
1) It stimulates ENaC at the principle cells and increases Na reabsorption → creates electronegativity → facilitates H secretion at the 𝜶 intercalated cells
2) Directly promotes H secretion by stimulating the H-ATPase at the luminal membrane
True or False: High tubular flow increases K secretion.
True
How does hypochloremic metabolic alkalosis cause hypokalemia?
Low chloride leads to relatively elevated bicarb in the filtrate in the nephron. The Na reabsorption is decreased at the proximal renal tubule due to hypovolemia from the underlying disease which cause hypochloremia (e.g. GI obstruction). The Na reabsorption at the ascending loop of Henle due to low chloride so Na-K-Cl channels don’t work that well. The Na reabsorption at the distal convoluted tubule is also decreased because of low Cl and Na-Cl channels don’t work well either. There will be increased concentration of Na reaching the connecting tubule and collecting duct. Na will be reabsorbed via ENaC and K as well as H will be exchanged and secreted into the filtrate due to electronegativity.
- If patient is also hypokalemia already, more hydrogen will be excreted (because K is not enough) and therefore worsening the metabolic alkalosis
Good Reference: https://eclinpath.com/chemistry/acid-base/compensation/renal-concentration/
Does serum or plasma contain higher K level? Why?
Serum
Because platelets release K during clotting process
What is the formula to calculate fraction excretion of potassium?
What percentage cutoff of FEk is used to differential renal and non-renal cause of hypokalemia?
FEk > 4% renal
FEk < 4% non-renal
Which breed of cat can have a inherited hypokalemic polymyopathy?
Burmese cat
What are the three big categories of causes for hypokalemia? List three differentials in each category.
1) Decreased intake
- Anorexia
- Administration of low potassium fluid
2) Move from ECF to ICF
- Alkalosis
- Insulin administration
- B2 agonist administration
- Catecholamine
3) Increased loss
- GI loss (v/d)
- CKD
- Post-obstructive diuresis
- Diuretic administration
- Primary hyperaldosteronism
How does hypokalemia cause muscle weakness?
1) hyperpolarization of the cell membrane
2) vasoconstriction and muscle ischemia (usually during exercise muscle will release K which leads to vasodilation and increase blood flow)
What is the proposed mechanism of hypokalemic nephropathy? What is its characteristics.
Characteristics: chronic tubulointerstitial nephritis
Renal vasoconstriction
Reduced medullary blood flow
Impaired renal angiogenesis
True or False: Hypokalemia increases renal ammoniogenesis.
True
*chronic metabolic acidosis also causes it
Normally, potassium supplementation shouldn’t exceed what rate?
0.5 mEq/kg/hr
What are the three big categories of causes for hyperkalemia? List three differentials in each category.
Increased intake
- Unlikely to be the sole cause of hyperkalemia
Move from ICF to ECF
- Insulin deficiency
- Acidosis (acute, mineral)
- Acute tumor lysis syndrome
- Rhabdomyolysis
- Reperfusion injury
Decrease excretion
- Anuric AKI
- Urethral obstruction
- Hypoadrenocorticism
What drugs can cause hyperkalemia?
ACEI, ARB (decreased aldosterone release)
Potassium-sparing diuretic
NSAID, heparin
Non-specific 𝜷 blocker (blocked beta adrenergic effect on Na-K ATPase)
Digoxin (inhibit Na-K ATPase)
What are the two main causes of pseudohyperkalemia?
Hemolysis
Thrombocytosis
What can we see on ECG in patients with hyperkalemia
Tall T wave
Prolonged P-R interval
Widened QRS complex
Atrial stanstill
Explain how does hyperkalemia cause changes on ECG.
1) initially, hyperkalemia cause increased resting membrane potential (less negative) → shortens the gap between resting membrane potential and threshold potential → higher cell excitability → shortens action potential duration and the tall T wave.
2) As the hyperkalemia worsens, it can decreased the available Na channels for the phase 0 → decreased Na channels cause decreased depolarization rate of phase 0 → prolonged action potential → widened QRS complex and prolonged PR interval
3) In severe hyperkalemia, resting membrane potential may increase to at the same level or above the threshold potential → unable to depolarize → atrial standstill
Reference:
1. Weiss JN, Qu Z, Shivkumar K. Electrophysiology of Hypokalemia and Hyperkalemia. Circ Arrhythm Electrophysiol. 2017 Mar;10(3):e004667. doi: 10.1161/CIRCEP.116.004667.
2. Parham WA, Mehdirad AA, Biermann KM, Fredman CS. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40-7. PMID: 16572868; PMCID: PMC1413606.
Explained the pathophysiology of osmotic demyelination syndrome.
When a patient is hyponatremic, the brain will exhibit some protective mechanism to maintain the brain cell volume. It will first increase the water excretion from the brain parenchyma to the CSF. It will also excrete some iorganic or organic osmoles out of the cells to maintain the similar osmolarity as the extracellular fluid.
When the hyponatremic is being correct, the opposite actions take place. The brain cells will take back the elextrolytes, synthesize intracellular proteins, and synthesize receptors to reuptake the previously secreted organic osmoles. This process usually takes days. So if the hyponatremic is being corrected too quickly, the ECF osmolarity will be markedly higher than the ICF osmolarity, which case net flux of water out of the cells and lead to osmotic demyelination.