Regulation of Potassium Balance Flashcards
Potassium:
• where is it located?
• How is it eliminated?
Location:
• INTRACELLULAR Fluid
Elimination:
• Almost completely excreted through the Kidney
Given the storage location and elimination of K, what are 3 important ways its concentration could be increased in the extracellular Fluid or Blood?
- K can simply be released from ICF storage pool into ECF and blood
- Cell Damage can release large amounts of K from the ICF and blood
- Impairment of Renal Excretion can also raise levels
What does potassium balance refer to?
• External vs. Internal Balance.
K+ levels in the ECF
External:
• Intake throught the Diet and Excretion through GI tract and Kidney
Internal:
• Distribution between intracellular and Extracellular Compartments
In what parts of the kidney is most K reabsorbed in the kidney?
• most important areas for reabsorption?
• Area that becomes significant in Hypokalemia?
• PCT, TDLH, TALH, DCT, CCD (basically everywhere except the thin limbs)
2 most important areas of Absorption.
• Proximal Convoluted Tubules
• Thick Ascending LOH
Hypokalemia:
• K collected in the collecting duct becomes important
What Channels are important for potassium transport in the Thick Ascending Loop of Henle?
• describe the co-dependence.
APICAL SIDE:
NK2C channel:
• Electroneutral Channel that Brings K+ into the cell
ROMK:
• renal outer medullary potassium channel
NK2C is dependent on ROMK for recycling of some K+ into the TALH lumen
BASOLATERAL SIDE:
NKA:
• Imports K+ into the back side of the celll
Where does Furosemide act?
Furosemide:
• works by binding the Cl- channel on NK2C and preventing K+ and Na+ reabsorption
What Channels are important in Principal Cells found in the Cortical and Medullary Collecting tubules (ducts). How do they related to K+ Balance?
• How do they work together?
• hormonal Influence?
*ALDOSTERONE - major hormonal influence in the Collecting Tubules (ducts)
Increases expression of the 3 major pumps in the PRINCPAL cells:
Apical: Na+ channel and K+ channel
Basolateral: NKA
How it works:
Basolateral Side: NKA maintains gradient of Low intracellular Na+ and High intracellular K+
Apical:
• Na+ Channel (ENaC)- pumps Na+ INTO principal cells Down its gradient
- K+ Channel (ROMK)- pumps K+ into LUMEN from principal cells DOWN its gradient
- Cl- Channel pumps Cl- OUT to interstitium via PARACELLULAR pathway
Where does potassium absorption mostly occur?
• Excretion?
Absorption:
• Proximal Convoluted Tubule
Excretion:
• Cortical and Medullary Convoluted Tubules
What are 3 factors that affect K+ secretion in principal cells of the Collecting Tubule (duct)?
• What are these factors dependent on?
- Serum Potassium Concentration - affects concentration gradient of K across the basolateral membrane
- Electrochemical Gradient Across the Luminal Membrane - depends on Na+ concentration
- K Permeability of Luminal Membrane - controlled by aldosterone
What would be a consequence on Potassium reabsorption if Na+ was not properly reabsorbed in the Proximal Convoluted Tubule or Loop of Henle?
- More Na will be delivered to the Collecting Duct
- More Na+ will be Pumped into Principal cells through ENaC => therefore more K+ will be EXCRETED by ROMK
Overall effect = excessive K+ excretion
What affect does excess aldosterone have on K+ metabolism in kidney?
• where is this function seen?
Aldosterone - upregulates ENaC, ROMK, and NKA
• Excess aldosterone will lead to an overall INCREASED secretion of K+ so that Na+ can be reabsorbed down its concentration gradient
How does the body adjust K+ uptake and secretion in the collecting duct (tubule) to account for changes in Dietary K+ intake?
Ex. HIGH K+ diet:
- Increases K concentration gradient
- Increased Serum Aldosterone to increase K+ secretion
T or F: Collecting tubule dysfunction of whole kidney dysfunction can lead to HYPERkalemia.
True, this is because K+ is no longer excreted in the Collecting Tubule (duct)
What are 3 general factors that will lead to Decreased Renal Postassium Secretion?
• what is the effect on serum levels of potassium with impaired secretion?
- Renal Failure
- Decreased Distal Tubular Flow
- Hypoaldosteronism
Impaired secretion will lead to HYPERkalemia
What are two general causes of Increased Renal Potassium Secretion?
• overall effect on serum potassium?
- INCREASED Na+ DELIVERY to COLLECTING Tubule
- INCREASED Aldosterone
**HYPOkalemia will result from these processes
What are some cases in which the amount of Na+ delivered to the Collecting Tubule is increased?
Diuretic Use - LOOP diuretics and Thiazide Diruetics that don’t work on ENaC prevent Na+ reabsorption
• by the time the Na+ travels down the ENaC you will have a huge Na+ gradient and K+ will get rapidly shuttled to lumen via ROMK
- Bartter’s Syndrome
- Gitelman’s Syndrome
What are some cases in which aldosterone may be increased causing hypokalemia?
Secondary:
• Prolonged Vomitting
• Nasogastric Suction
Primary:
• Hyperaldosteronism
What pump is important in maintaining internal balance?
NKA - almost all factors that affect internal K balance work through the NKA pump
*note: K+ is constantly exiting through K+ Channels
What are 3 factors that are important in changing K+ concentration inside of Cells?
- Plasma K concentration
- Insulin
- Epinephrine
How does insulin work to Change K+ balance?
indirectly INCREASES intracellular K+
MOA:
• stimulates NaH exchanger which moves Na+ inside the cells which eases the gradient that NKA must work against
How does Epinephrine work to Change K+ balance?
Acts on Beta receptors to INCREASE intracellular K+
MOA:
• Stimulates NKA
What would a Beta Blocker do to Intracellular and Extracellular Potassium?
• albuterol?
Beta Blocker:
• Prevents E binding and thus reduces NKA stimulation leading to a REDUCTION in INTRACELLULAR K+
• While less K+ is influxing there is still a good amout EFFLUXING to ECF of the cell so BETA BLOCKER RAISE EXTRACELLULAR K+ concentration
Albuterol:
• Has essentially the same effect as epinephrine
What effect does low serum K+ have on K+ influx and efflux from cells?
Low Serum K+ will tend to PULL K+ OUT OF CELLs down its gradient
Other Factors that Affect Internal Potassium Balance
• Acid-Base Disturbance
• Plasma Tonicity
• Cell Lysis and Cell Proliferation
Other Factors that Affect Internal Potassium Balance
• Acid-Base Disturbance
• Plasma Tonicity
• Cell Lysis and Cell Proliferation
What affect do Acid Base disturbances have on K+ levels inside of cells?
• which are more disruptive of the H/K balance; metabolic or respiratory defects?
• K+ and H+ shift Reciprocally
ACIDOSIS:
• Metabolic Defects cause more of a disturbance than Respiratory Disturbances
• causes HYPERKALEMIA because H+ is flowing into cells and K+ then flows out
ALKALOSIS:
• leads to HYPOKALEMIA
Which will have more of a hyperkalemia associated with it:
• metabolic acidosis due to Mineral Acid or due to Organic Acid
Mineral Acids tend to have a greater effect on K+ levels
What is the effect of Hypertonicity on K+ levels in the ECF?
ECF = Hypertonic
Result is HYPERKALEMIA** (more K+ in the ECF)
- H2O diffuses out of the cell as a result
- Some K+ comes with the H2O
Overall:
• Loss of Intracellular H2O increases intracellular K+ concentration
• Increases K+ gradient and some K+ diffuses through the potassium channel
What are some common causes of Hypertonicity?
• Diabetic Ketoacidosis or Diabetic Hyperosmolar state (caused by inc. Extracellular Glucose concentration)
What are some pathogenic causes of cell lysis and cellular proliferation that often cause disruption in K+ balance?
Cell Lysis => HYPERkalemia:
• Rhabdomyolysis
• Red Cell Lysis
Cell Proliferation => HYPOkalemia
• Cancer
When is a person considered to be Hyperkalemic?
• 3 general causes of hyperkalemia?
Serum Potassium greater than 5.5
3 causes:
- Excessive Potassium Intake
- Decreased Renal Excretion
- Internal Redistribution
What are some causes of Decreased Renal Excretion of K+?
• common condition that these lead to?
All lead to HYPERKALEMIA
- Acute and Chronic Renal Failure
- Distal Tubular Dysfunction
- Decreased Distal Tubular Flow
- Hypoaldosteronism
What are some causes of Defective Potassium Distribution that cause HYPERKALEMIA?
- Insulin Deficiency
- ß2-adrenergic Blockade
- Hypertonicity
- Acidemia
- Cell Lysis - Rhabdomyolysis
What are the EKG manifestations of Hyperkalemia as the disease progresses?
- Tall Peaked T wave (from influx of K1, ATP, and Ach potassium channels)
- Widened QRS
- Prolonged PR
- Loss of P-wave
- Further QRS widening
- Ultimately V-tach
What are the two reasons that we want to treat hyperkalemia?
- Prevent Cardiac Arrythmias by Stabilization of Cardiac Muscle Cells
- Lower serum K by moving it either inside cells or outside of the body
What treatment do we use to stabilize Cardiac muscle cells in Hyperkalemia?
• Intravenous Calcium
What are two methods to lowing Serum K+?
• what treatments do we give to achieve this?
Moving K+ inside of Cells and OUT of ECF
• Insulin
• ß Agonists
• Bicarbonate
Moving K+ outside of the Body
• Diuretics
• Cation Exchange Resins
• Dialysis
What drugs should be given first to someone that comes in hyperkalemic?
• 2nd?
• 3rd?
How long will it take each of these treatments to kick in and how long will they last?
1st:
• CALCIUM: Onset 1-3min; Duration 30-60 min
2nd:
• INSULIN: Onset 30 min; Duration 4-6 hours
• BICARB: Onset 15 min; Duration 1-2hrs
• ALBUTEROL: Onset 30 min; Duration 2-4 hrs
3rd:
• FUROSEMIDE: Onset 5 min; Duration 2 hrs
• K-EXCHANGE RESIN: Onset 2-3 hrs; Duration 4-6 hrs
What are the 3 general Causes of Hypokalemia?
- Reduced Potassium Intake (via diet)
- Internal Redistribution
- Increased Renal or GI Excretion
What are some causes of External Potassium loss (aka potassium that’s actually leaving the body, not just moving compartements)?
- Gastrointestinal Losses
- Cutaneous Losses
- Renal Losses
What are some causes of Internal Redistribution of potassium leading to Hypokalemia?
- Insulin Excess
- Catecholamine Excess
- Alkalemia
- Cell Proliferation
What are two causes of NORMOTENSIVE Hypokalemia?
- Hypokalemia with METABOLIC acidosis
2. Hypokalemia with METABOLIC Alkalosis
What are some causes of Hypokalemia with Metabolic Alkalosis?
- Diuretics - LOOP and THIAZIDE
- Prolonged Vomiting
- Nasogastric Suction
- Bartter’s Syndrome
- Gitelman’s Syndrome
What are some causes of Hypokalemia with Metabolic Acidosis?
- Renal Tubular Acidosis (RTA) - Type 1 or 2
* Ureteral Diversion - Into ileum or to Sigmoid
Differentiate the causes of Hypokalemia with Metabolic Acidosis on the basis of where the problem arises.
Proximal Convoluted Tubule:
• RTA2 (renal tubular acidosis) - K+ and HCO3- can be reabsorbed in PT
Thick Ascending Loop of Henle:
• Furosemide - Block NK2C
• Bartter’s - ineffective NK2C
Extra sodium in carried to CD where it gets exchanged for K+ (via ENaC and SOMK)
Distal Tubule:
• Thiazide Diuretics - blockage of Na-Cl transporter
• Gitleman’s Syndrome - Blockage of Na-CL transporter
Extra sodium in carried to CD where it gets exchanged for K+ (via ENaC and SOMK)
Collecting Duct Dysfunction:
• RTA type 1 hypokalemia
What are the 3 outcomes that result from excess H+ and Cl- loss from vomitting?
• how do they come about?
Elevated Serum Aldosterone:
• causes increase Na+ reabsorption
***Result: Increases Electronegativity of Lumen
Loss of Cl- from HCl in vomit:
• Less Cl- delivered to distal tubule
• MORE non-absorbable HCO3- to distal tubule (because it can’t be absorbed in the LOH like Cl)
***Result: Increased Electronegativity of Lumen
Elevated Levels of HCO3- in BLOOD:
• due to loss of H+ (LeChatelier’s pushes equn. to the right)
ELECTRONEGATIVITY in Tubular Lumen causes:
• Increased SECRETION of K+ and H+
3 ULTIMATE OUTCOMES:
• Hypokalemia
• Metabolic Alkalosis
• PARADOXICAL Aciduria
What are some causes of HYPERTENSIVE hypokalemia?
Diseases are caused by TOO MUCH ALDOSTERONE - either directly or through too much renin
Hyperreninemia:
• Renal Artery Stenosis
• Renin-Secreting Tumor
Primary Hyperaldosteronism (Conn’s Syndrome):
• Adrenal Hyperplasia
• Adrenal Tumor
*OR can be caused by too much Glucocorticoid that can weakly bind aldosterone receptor
Cushing’s Syndrome
• Exogenous, Adrenal, Pituitary
Congenital Adrenal Hyperplasia
• Enzymatic Defects in Cortisol Biosynthesis
What is the most common cause of excess glucocorticoid that caueses Hypokalemia with Hypertension?
• why are Hypokalemia and HTN seen?
EXOGENOUSLY induced CUSHING’s Syndrome
• ppl. w/ transplants, COPD, Autoimmune disease etc. that require long term steriod
Hypokalemia:
• Caused by increased Na+ absorption (via more ENaC, ROMK, NKA production)
• Na+ is indirectly exchanged for K in the lumen as it travels down its gradient
Hypertension:
• Na+ retention increases Blood Volume
What EKG changes are associated with Hypokalemia?
- Flat - T wave
- Prominent- U wave
- Depressed - ST Segment
**U-wave is Pathopneumonic for Hypokalemia
Contrast the Arrhythmia created by hyperkalemia and hypokalemia.
Hyperkalemia:
• BRADYARRYTHMIA
Hypokalemia:
• TACHYARRYTHMIA
T or F: severe symptoms are often associated with chronic hypokalemia.
FALSE, chronic hypokalemia is usually asymptomatic
What symptoms are seen in the following systems when someone gets hypokalemic? • Cardiac • Smooth Muscle • Skeletal Muscle • Renal
Cardiac:
• EKG changes
• (tachy) Arrhythmias
Smooth Muscle:
• Hypertension
• Intestinal ileus
Skeletal Muscle:
• Weakness
• Rhabdomyolysis
Renal:
• Nephrogenic Diabetes Insipidus
What are two general treatments administered for hypokalemia?
- Potassium Replacement
2. Potassium Sparing Diuretics
Why determining someone’s potassium deficit so difficult?
We can only measure Serum Potassium as an estimate of INTRACELLULAR potassium, which is where the actual deficiency is.
What is the problem with rapid infusion of potassium for someone with Potassium Deficiency?
Rapid K+ infusion can cause Cardiac Arrest
What specific compound would you give someone who was Hypokalemic?
• how would you do this?
KCl or KPO4 can be given ONLY if there is an accompanying phosphate deficiency
SLOW IV infusion over a period of 2 hours
You can also give ORAL KCl
What is the typical treatment for CHRONIC hypokalemia?
POTASSIUM SPARING DIURETICS:
Aldosterone Receptor Blockers/Mineralcorticoid antagonists
• Spironolactone
• Eplernone
ENaC sodium Channel Inhibitors
• Amioride
• Triamterene
These work because they act on the source in the Collecting tubule that typically creates the hypokalemia
