Regulation of Potassium Balance Flashcards

1
Q

Potassium:
• where is it located?
• How is it eliminated?

A

Location:
• INTRACELLULAR Fluid

Elimination:
• Almost completely excreted through the Kidney

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2
Q

Given the storage location and elimination of K, what are 3 important ways its concentration could be increased in the extracellular Fluid or Blood?

A
  1. K can simply be released from ICF storage pool into ECF and blood
  2. Cell Damage can release large amounts of K from the ICF and blood
  3. Impairment of Renal Excretion can also raise levels
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3
Q

What does potassium balance refer to?

• External vs. Internal Balance.

A

K+ levels in the ECF

External:
• Intake throught the Diet and Excretion through GI tract and Kidney

Internal:
• Distribution between intracellular and Extracellular Compartments

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4
Q

In what parts of the kidney is most K reabsorbed in the kidney?
• most important areas for reabsorption?
• Area that becomes significant in Hypokalemia?

A

• 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

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5
Q

What Channels are important for potassium transport in the Thick Ascending Loop of Henle?
• describe the co-dependence.

A

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

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6
Q

Where does Furosemide act?

A

Furosemide:

• works by binding the Cl- channel on NK2C and preventing K+ and Na+ reabsorption

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7
Q

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?

A

*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
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8
Q

Where does potassium absorption mostly occur?

• Excretion?

A

Absorption:
• Proximal Convoluted Tubule

Excretion:
• Cortical and Medullary Convoluted Tubules

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9
Q

What are 3 factors that affect K+ secretion in principal cells of the Collecting Tubule (duct)?
• What are these factors dependent on?

A
  1. Serum Potassium Concentration - affects concentration gradient of K across the basolateral membrane
  2. Electrochemical Gradient Across the Luminal Membrane - depends on Na+ concentration
  3. K Permeability of Luminal Membrane - controlled by aldosterone
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10
Q

What would be a consequence on Potassium reabsorption if Na+ was not properly reabsorbed in the Proximal Convoluted Tubule or Loop of Henle?

A
  • 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

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11
Q

What affect does excess aldosterone have on K+ metabolism in kidney?
• where is this function seen?

A

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

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12
Q

How does the body adjust K+ uptake and secretion in the collecting duct (tubule) to account for changes in Dietary K+ intake?

A

Ex. HIGH K+ diet:

  1. Increases K concentration gradient
  2. Increased Serum Aldosterone to increase K+ secretion
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13
Q

T or F: Collecting tubule dysfunction of whole kidney dysfunction can lead to HYPERkalemia.

A

True, this is because K+ is no longer excreted in the Collecting Tubule (duct)

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14
Q

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?

A
  1. Renal Failure
  2. Decreased Distal Tubular Flow
  3. Hypoaldosteronism

Impaired secretion will lead to HYPERkalemia

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15
Q

What are two general causes of Increased Renal Potassium Secretion?
• overall effect on serum potassium?

A
  1. INCREASED Na+ DELIVERY to COLLECTING Tubule
  2. INCREASED Aldosterone

**HYPOkalemia will result from these processes

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16
Q

What are some cases in which the amount of Na+ delivered to the Collecting Tubule is increased?

A

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
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17
Q

What are some cases in which aldosterone may be increased causing hypokalemia?

A

Secondary:
• Prolonged Vomitting
• Nasogastric Suction

Primary:
• Hyperaldosteronism

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18
Q

What pump is important in maintaining internal balance?

A

NKA - almost all factors that affect internal K balance work through the NKA pump

*note: K+ is constantly exiting through K+ Channels

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19
Q

What are 3 factors that are important in changing K+ concentration inside of Cells?

A
  1. Plasma K concentration
  2. Insulin
  3. Epinephrine
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20
Q

How does insulin work to Change K+ balance?

A

indirectly INCREASES intracellular K+

MOA:
• stimulates NaH exchanger which moves Na+ inside the cells which eases the gradient that NKA must work against

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21
Q

How does Epinephrine work to Change K+ balance?

A

Acts on Beta receptors to INCREASE intracellular K+

MOA:
• Stimulates NKA

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22
Q

What would a Beta Blocker do to Intracellular and Extracellular Potassium?
• albuterol?

A

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

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23
Q

What effect does low serum K+ have on K+ influx and efflux from cells?

A

Low Serum K+ will tend to PULL K+ OUT OF CELLs down its gradient

24
Q

Other Factors that Affect Internal Potassium Balance
• Acid-Base Disturbance
• Plasma Tonicity
• Cell Lysis and Cell Proliferation

A

Other Factors that Affect Internal Potassium Balance
• Acid-Base Disturbance
• Plasma Tonicity
• Cell Lysis and Cell Proliferation

25
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
26
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
27
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
28
What are some common causes of Hypertonicity?
• Diabetic Ketoacidosis or Diabetic Hyperosmolar state (caused by inc. Extracellular Glucose concentration)
29
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
30
When is a person considered to be Hyperkalemic? | • 3 general causes of hyperkalemia?
Serum Potassium greater than 5.5 3 causes: 1. Excessive Potassium Intake 2. Decreased Renal Excretion 3. Internal Redistribution
31
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
32
What are some causes of Defective Potassium Distribution that cause HYPERKALEMIA?
* Insulin Deficiency * ß2-adrenergic Blockade * Hypertonicity * Acidemia * Cell Lysis - Rhabdomyolysis
33
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
34
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
35
What treatment do we use to stabilize Cardiac muscle cells in Hyperkalemia?
• Intravenous Calcium
36
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
37
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
38
What are the 3 general Causes of Hypokalemia?
1. Reduced Potassium Intake (via diet) 2. Internal Redistribution 3. Increased Renal or GI Excretion
39
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
40
What are some causes of Internal Redistribution of potassium leading to Hypokalemia?
* Insulin Excess * Catecholamine Excess * Alkalemia * Cell Proliferation
41
What are two causes of NORMOTENSIVE Hypokalemia?
1. Hypokalemia with METABOLIC acidosis | 2. Hypokalemia with METABOLIC Alkalosis
42
What are some causes of Hypokalemia with Metabolic Alkalosis?
* Diuretics - LOOP and THIAZIDE * Prolonged Vomiting * Nasogastric Suction * Bartter's Syndrome * Gitelman's Syndrome
43
What are some causes of Hypokalemia with Metabolic Acidosis?
* Renal Tubular Acidosis (RTA) - Type 1 or 2 | * Ureteral Diversion - Into ileum or to Sigmoid
44
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
45
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
46
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
47
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
48
What EKG changes are associated with Hypokalemia?
* Flat - T wave * Prominent- U wave * Depressed - ST Segment **U-wave is Pathopneumonic for Hypokalemia
49
Contrast the Arrhythmia created by hyperkalemia and hypokalemia.
Hyperkalemia: • BRADYARRYTHMIA Hypokalemia: • TACHYARRYTHMIA
50
T or F: severe symptoms are often associated with chronic hypokalemia.
FALSE, chronic hypokalemia is usually asymptomatic
51
``` 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
52
What are two general treatments administered for hypokalemia?
1. Potassium Replacement | 2. Potassium Sparing Diuretics
53
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.
54
What is the problem with rapid infusion of potassium for someone with Potassium Deficiency?
Rapid K+ infusion can cause Cardiac Arrest
55
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
56
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***