K+ metabolism Flashcards
Normal American diet contain approximately ___ meq of K
100 meq
What is the intracell conc on K+?
120-140 meg
What is the extracell conc of K+?
4-5 meq
Where is the majority of K+ stored?
muscle
*other significant storage include liver, RBC, and bone
If the kidney is functioning normally, ____% of dietary K+ is excreted through the kidney
almost 100
What is internal K+ balance?
regulation of the distribution of K+ between the ICF and ECF
What is K+ external balance?
regulation of TBk+ thru alterations in K+ intake and excretion (GI, renal)
Where does most of the K+ reabs occur?
PT and TALH
Where is the only place K+ is secreted?
principal cells in cortical and outer medullary CD
How much K+ is reabs in the PT?
65%
How much K+ is reabs in the TALH?
35%
Describe the movement of K+ in cells at TALH
Basolateral:
-NaK-ATPase antiport brings K+ into the cell
Apical:
- NaKCl co transporter brings K+ into cell
- K+ channel brings K+ out of cell and into lumen (moves here bc the Na reabsorption creates a - charge in lume)
-paracellular diffusion from lumen to blood thru tight junction
What happens to the K+ that flows into the lumen thru the apical K+ channel?
Not excreted!
- “re-used” for NaKCl co-transporter
- creates a + charge in lumen to repel other cations (Na, K, Ca, Mg) to be transported/diffuse paracellularly
Is K+ normally excreted?
no, its almost 100% reabs
WHat effect does also have on the principal cells in the CD?
goes into the nucleus to bind a nuclear receptor to inc the expression of
- Na-K pump
- Na epithelial channel (apical side)
- K+ channel (apical side)
What are the factors that effect K+ secretion?
- conc gradient (high serum K+ –> inc secretion)
- electrical gradient (Na needs to have been reabs in PT to create a - charge in lumen)
- K+ permeability (# open K+ channels on luminal side <-aldo)
graph slide
9
What are causes of decreased renal potassium secretion (4)?
- renal failure
- DT dysfunction (part of the kidney that secreted K+)
- decreased distal tubular flow = decrease in distal delivery of Na
- hypoaldosteronism or inhib of aldo
What are causes of hyperkalemia?
same as those that decrease K+ secretion
- renal failure
- DT dysfunction (part of the kidney that secreted K+)
- decreased distal tubular flow = decrease in distal delivery of Na
- hypoaldosteronism or inhib of aldo
Slides
11
slide
12
What can cause increased reanl potassium secretion?
- diurretics (loops and thiazide)
- prolonged vomiting
- nasogastric suction
- Bartter’s syndrome
- Gitelman’s syndrome
- hyperadosteronism
*inc secretion caused hypokalemia
How do diurectic, vomiting, and Bartter’s and Gitelman’s cause hypokalemia?
increase distal Na deliver –> increase K secretion
How is internal K balance maintained?
adjusting K transport across the cell membrane
The concentration gradient of K (ICF > ECF) is responsible for passive transport of ____ through _____.
K+ thru K+ channels
T or F: the concentration gradient of K between intracellular and extracellular fluid is maintained by transporting K from extracellular fluid to cells against the concentration gradient.
true
What is the main pathway to transport if K into cells?
NaK-ATPase
The NaK ATPase pump transports ___ Na out of the cells and ___ k into the cells
3 Na out and 2 K in
T or F: all the factors that affect the internal K balance works through the NaK ATPase pump
T
What are 7 factors that affect the internal balance of K+?
plasma K conc insulin Epi Acid base disturbance plasma tonicity cell lysis cell proliferation
How does an inc in plasma K+ affect the internal balance of K+?
inc in plasma [K+] decreases K+ movement outside of the cell
How does insulin affect the internal balance of K+?
insulin moves K+ inside cells by
- stimulates NaH exchanger to move Na inside the cell. T
- this activates NaK ATPase pump
- K+ is moved inside cells
How does epinephrine affect the internal balance of K+?
Stimulates Beta2 receptor which activates the NaK ATPase –> K+ goes into cells
WHat effect does activation of the alpha 2 receptor have on K+ internal balance?
activation of alpha 2 inhibits the NaK ATPase and will inc plasma K+
How can diabetes effect the K+ plasma levels?
they have defcicint insulin = dec activity of NaK ATPase = more K+ in ECF
*the K+ channel will not not be affected by hormones and will continue to move K+ from the ICF–> ECF
What affect does albuterol have on a plasma K+ levels?
it binds Beta2 receptor to stimulate the NaK-ATPase (moves K+ from ECF to ICF)
*Tx for hyperkalemia
How will an acid base disturbance affect internal balance of K+?
dec in pH –> hyperkalemia
inc pJ –> hypokalemia
T or F: respritory acid-base distrubances have a greater effect than metabolic acid-base disturbances
F: metabolic disturbances have a greater effect and respiratory
T or F: Metabolic acidosis due to organic acids (ketoacidosis, lactic acidosis) have smaller effects than do acidosis due to mineral acids
T
How does tonicity affect the internal balance of K+?
hypertonicity (i.e. hypernatremia or hyperglycemia) or hyperosmolar in the ECF will cause water to flow from ICF to ECF. The water that flows from the ICF will drag K+ with it as it moves (solvent drag)
Also, as water moves out it of the ICF, the intracellular concentration increases –> increases the conc gradient –> more K+ moves into ECF thru the K+ cannel
–> hyperkalemia
What effect does a state of diabetic ketoacidosis have on the K+ internal balance?
in diabetic ketoacidosis, there is a hyperosmolar/hypertonic state in the ECF (hyperglycemia) that cuases water to flow into ECF, dragging K+ with it and inc intracell cocn of K+ –> K+ moves with the conc/into ECF thru K+ channels
Acidosis also contributes to hyperkalemia
How does cell lysis affect the internal balance of K+?
when a cell lysis it releases the K+ that was stored in the cell into the extracell space
*ex: rhabdomyolysis, RBC injury/hemolysis
How does cell proliferation affect the internal balance of K+?
K+ is rapidly taken up by proliferating cells, causing extracell K+ to decrese = hypokalemia
Leukemia will cause a (hyper- or hypo-) kalemic state.
hypo (cell proliferation rapidly takes up extracell K+)
Hyperkalemia is considered to be > ____ meq/L of potassium.
> 5.5 meq/L
What are 3 general cuases of hyperkalemia? (think like Dr. Nace)
- too much intake
- decrease excretion
- internal redistribution
Hyperkalemia can be caused by decreased renal excretion, what specifically can cause that?
acute or chronic renal failure
dec distal tubular flow
distal tubular dysfunction (where is it secreted
hypo-aldosteronism
What can cause an internal redistribution of K+ leading to hyperkalemia?
insulin deficiency Beta2 adrenergenic blockade hypertonicity acidemia cell lysis
Describe the EKG manifestations of hyperkalemia.
plasma K+ mEq/L –> EKH changes
4 –> normal
6 –> peaked T waves
8 –> wide QRS complex, shortened QT interval, prolonged PR interval
10 –> further widening of QRS complex, absent P wave
12 –> sine wave morphology (ventricular tachycardia)
What are the sigs and symptoms of hyperkalemia?
Cardiac:
- EKG changes
- cardiac conduction defects
- arrhythmias (bradyarrythmia)
Neuromuscular:
- asceending weakness
- ileus
What are the treatment options for hyperkalemia?
- Sblz cardiac muscle cells
- lower serum K+ by moving K+ inside cells
- insulin, Beta agonists, Bicarbonate
- lower serum K+ by moving K+ outside the body
- diuretics, cation exchange resins, dialysis
Where does insulin act to treat hyperkalemia?
inc activity of Na:H ion exchanger
Where does bivarbonate act to treat hyperkalemia?
inc activity of Na:H exhanger
Will insulin cause acidosis?
no, but it needs to be given with glc to prevent hypoglycemia
*apparently, it doesn’t inc extracell [H+] enough to cause acidosis
What treatment option for hyperkalemia is the quickest?
Calcium
How does calcium admin treat hyperkalemia?
antagonizes membrane depolarization from in extracell K+
What is the root cause of most of the signs and symptoms assc with hyperkalemia?
from the depolarization of resting cell membrane potential in myocytes and neurons
*Prolonged depolarization decreases membrane Na+ permeability through the inactivation of voltage-sensitive Na+ channels producing a reduction in membrane excitability
Hypokalemia is considered to be < ____ meq/L of potassium.
< 2.5 mEq/L
What are the 3 general causes of hypokalemia? (think like Dr. Nace)
decreased intake
increased renal excretion
internal redistribution
How is K+ lost externally?
GI, skin, renal
What causes K+ to be redistributed internally leading to hyokalemia?
insulin excess
catecholamine excess
alkalemia
cell proliferation
What can be a cause of hypokalemia with normal BP and metabolic alkalosis?
loop and thiazide diuretics prolonged vomiting nasogastric suction Bartter's syndrome Gitleman's syndrome
What can be a cause of hypokalemia with normal BP and metabolic acidosis?
RTA uretral diversion (uretero-ileostomy, utereo-sigmoidostomy)
How does RTA II cause hypokalemia?
prevents reabs if K+ in PT
How does Girleman’s cause hypokalemia?
blocks NaCl transporter
How can thiazides cause hypokalemia?
blocks NaCl transporter
How does RTA I cause hypokalemia?
defect in CD that increases K+ excretion in the urine
How cam furosemides cause hypokalemia?
blocks NaKCl channel and delivers more K to CD
How does Bartter’s cause hypokalemia?
blocks NaKCl channel and delivers more K to CD
What are hypertensive disorders assc with hypokalemia?
hyperreninemia
Conn’s syndrome (primary hyperaldosteronism)
Cushing’s syndrome (glucocorticoid excess)
congenital adrenal hyperplasia
What can cause hyperrninemia leading to hypokalemia?
renal artery senosis (inc RBF and signals for renin production)
renin-secreting tumor
What can cause conn’s syndrome leading to hypokalemia?
adrenal hyperplasia and adrenal tumors
*inc aldo which inc NaK ATPase activity and the number of luminal K channels
What can cause cushing’s syndrome leading to hypokalemia?
exogenous, pituitary, or adrenal production of excess glucocorticoids
*works just like also to nc NaK ATPase activity and the number of luminal K channels
How does congenical adrenal hyperplasia lead to hypokalemia?
there are enzymatic defects in cortisol biosynthesis –> excess aldo precursor –> inc aldo –> inc NaK ATPase activity and the number of luminal K channels
What are the clinical manifestations of acute hypokalemia?
Cardiac:
- EKG changes
- arrhythmias-tachyarrythmias
Smooth muscle:
- hypertension
- ileus
Skeletal musle:
- weakness
- rhabdomyolysis
Renal:
-nephrogenic diabetes insidius
Describe the EKG manifestations of hypokalemia.
normal –>
Flat T wave –>
prominant U wave –>
Depressed ST segment
What are the clinical manifestations of chronic hypokalemia?
asymptomatic
What is the treatment for hypokalemia?
K+ replacement (give large amounts slowly)
- given usually as KCL, KPO4
- oral or IV
K+ sparing diuretics
- eNaC inhib (amiloride, triamterene)
- mineralcorticoid antagonists (spironalactone, eplerenone)
What are the 2 most important determinants of K+ secretion?
aldo levels
distal Na delivery
T or F: both high and low serum K+ levels can result in serious cardiac rhythm abnormalities
T
