First Pass Miss Flashcards
What effect to catecholamines have on potassium homeostasis via the Beta-2 receptors? What would propranolol do?
B2 receptors promote entry of potassium into primarily skeletal muscle and liver cells -> activate Na/K ATPase
Propanolol would block this B2 receptor effect and may contribute to hyperkalemia
alpha2 agonists blocks insulin release and predisposes to hyperkalemia as well
How does insulin affect K+?
Insulin promotes entry of K+ into skeletal muscle directly by increasing the number of Na/K ATPases
Insulin stimulates Na/H exchanger in liver, bringing Na+ into the cell. Every 3 turns of this leads to 2 K+ brought into the liver cell via the Na/K ATPase
Insulin allows K+ entry into cells passively.
What effect does metabolic acidosis have on potassium homeostasis and why?
Causes hyperkalemia
- > decreased ability to run Na/H antiporter since ECF is already acidic
- > less Na+ inside the cell to run Na/K ATPase -> potassium stays outside of the cells
Is the hyperkalemic effect of metabolic acidosis worse with mineral or organic acids?
Worse with mineral acids, since the anions can’t enter the cell and must stay in the blood
Organic acids can be transported into the cell so the effect of hyperkalemia will be less dramatic. This is because organic acids entering the cell will reduce cellular pH, so Na/H antiporter can still be run to push H+ into ECV, bring Na+ in, and keep K+ balance normal.
What effect will hyperosmolarity have on blood potassium levels and why?
Hyperosmolarity - increased K+ levels
- > Osmotic drag = K+ leaves the cells with water
- > Decreased water inside cells also concentrates K+, passive movement out of cells
How is the majority of the potassium reabsorbed in the kidney?
Majority in proximal tubule
Early proximal tubule - due to solvent drag, from movement of water and sodium into cells, concentrating K+
Late proximal tubule - due to paracellular diffusion, as lumenal potential becomes positive
What is the general underlying problem of the aldosterone paradox?
High K+ levels stimulate aldosterone secretion, which preferentially leads to K+ excretion within minimal Na+ reabsorption
Angiotensin II also stimulates aldosterone secretion, which preferentially leads to Na+ reabsorption with minimal K+ excretion
What justifies the aldosterone paradox?
Angiotensin II - stimulates the WNK kinases and reabsorbs more Na+ via the NCC in the early DCT so less sodium load is delivered to late DCT / principle cells, preventing K+ losses
K+ stimulation of aldosterone - WNK kinases not affected, to K+ is lost more readily, and same amount of Na+ is reabsorbed
What is the function of the WNK kinases? What else are they stimulated by other than Angiotensin II?
They lead to removal of ROMK channels in the distal nephron -> Also stimulated by low blood potassium levels
-> make sense because we want to save potassium from excretion
What effect does pH have on K+ reabsorption and why?
Acidemia - increases K+ reabsorption, can quickly run H/K antiporter -> acidemia is associated with hyperkalemia
Alkalemia - decreases K+ reabsorption, cannot run H/K antiporter -> alkalosis is associated with hypokalemia
What endocrine abnormalities are induced by hypokalemia?
Decreased insulin secretion (already too much K+ in cells)
Increased renin with decreased aldosterone (aldosterone paradox)
-> aldosterone would waste K+
->also remember than WNK kinases are stimulated with hypokalemia -> reduce ROMK levels in collecting duct, preventing K+ wasting
What are the causes of renal K+ loss without HTN?
Vomiting Diuretics - increased Na+ load Bartter syndrome Gitelmans syndrome Renal tubular acidoses types I and II
What is pseudohyperkalemia?
- High K+ due to difficulty with venipuncture which causes local mechanical trauma and muscle K+ release.
- Serum H+ is always higher K+ than plasma K+ when measured in the lab because of clotting process leads to lysis. High WBC / platelet counts can make this effect greater
In what conditions will inadequate urinary excretion lead to hyperkalemia?
- Very late stage renal failure - GFR <20
- Effective circulatory volume depletion - K+ excretion limited by small urine volume
- Hypoaldosteronism - Type IV RTA
What are the clinical ECG manifestations of hyperkalemia? Are these more serious than hypokalemia?
Wide QRS with peaked T waves -> arrhythmias
QT intervals are shortened -> rapid repolarization
-> can cause bradycardia
Widened QRS with severe hyperkalemia can lead to loss of P waves and eventual Vfib
More serious than hypokalemia, more likely to cause emergent arrhythmia
What are the clinical muscle and endocrine manifestations of hyperkalemia?
Muscle weakness and paralysis
Endocrine - increased aldosterone and increased insulin secretion, while decreasing renin
aldosterone paradox
How does plasma osmolality relate to plasma Na concentration, conceptually?
Directly proportional. Thus, total body water content can be estimated by Na concentration, but ECF volume cannot be estimated by Na concentration (needs total body Na, a clinical assessment by physical exam or direct intravascular monitoring)
What is the formula for calculating plasma osmolality? Give the normal value?
2*Na + (glucose / 18) + (BUN / 2.8)
Na in mmol/L - because each Na is accompanied by an anion
Glucose in mg/dL
BUN in mg/dL
Normal value is around 290 mOsm / kg water
Plasma osmolality is inversely proportional to total body WATER CONTENT
What is the difference between water depletion and volume depletion? What is dehydration talking about?
Water depletion - depletion of total body water (increased Na concentration / osmolality) -> dehydration refers to this
Volume depletion - depletion of ECF volume / total body Na. Dehydration should not refer to this, but sometimes sloppily applied
What are the two cases when plasma osmolality is NOT proportional to plasma [Na]?
Pseudohyponatremia:
- Artifactual hyponatremia
- > elevated solid components lead to the same volume of blood having less plasma in it -> lower measured sodium per volume of blood drawn
- Hyperlipidemia
- Hypergammaglobulinemia (multiple myeloma - Hyperosmolal hyponatremia
- > caused by diabetes, sugar pulls water out of cells, diluting ECV
- > treated by insulin
- > Na will recover 1.6mM for every 100 mg/dL above 200 mg/dL blood sugar
What area of the brain regulates plasma osmolality? How do they relate to the BBB? how do they work? What are the osmoreceptors type?
Subfornical organ (beneath hippocampus) and organum vasculosum of lamina terminalis (OVLT)
Outside of BBB, have TRPV1 osmoreceptors and angiotensin II receptors
Other than angiotensin II, low BP, low blood volume, and high plasma osmolality, what other factors stimulate ADH release?
Other stress-related stimuli:
Nausea
Hypoxia
Hypercapnia
Pain (nociceptors)
-> keep these all in mind as causes of normal ECV hyponatremia
What effect does ADH have on the kidneys? What receptor does it bind?
Increases solute absorption via TALH (NKCC) and urea absorption by collecting duct to increase medullary osmotic gradient (greater concentrating power)
-> upregulates UT1/UT2 transporters
Binds V2 receptors. Increases Aquaporin 2 expression in collecting duct (cAMP mechanism). Aqp3 also has a minor effect.
Where is urea synthesized, filtered, reabsorbed, and secreted?
Synthesized - liver
Filtered - glomerulus, freely
Reabsorbed - inner medullary collecting duct, taken up by ascending vasa recta
Secreted - proximal straight tubule - after acquisition from ascending vasa recta
Some urea from ascending vasa recta is also transferred to adjacent descending vasa recta