2.6 - Crr - Week 10

Front 1

___ plays a key role in generation of the resting membrane potential, which influences many biologic functions.

Back 1

Potassium

Front 2

Describe (in order) the EKG abnormalities we see in a hyperkalemic state, starting with a normal EKG and normal potassium concentration.

Back 2

1 - Normal EKG
2 - "Take your right hand and 'pinch' the T wave" (a T wave with a peak like a mountain)
3 - "Now take your left hand and smoosh the P wave flat." (flattened P wave)
4 - "Now move them apart" (QRS complex gets wider and wider from this point on as [K+] increases)

Front 3

Surpluses or deficits of K+ predispose to ____ _______.

Back 3

cardiac arrhythmias

Front 4

Immediate/Short-Term/Quick changes in [K+] takes place via...

Back 4

exchange with the intracellular fluid (translocation into cells)

Front 5

Factors promoting K+ uptake into cells

Back 5

- [K+]p
- insulin*** (usually give some glucose with it)
- epinepherine***
- metabolic alkalosis
- aldosterone

Front 6

The major way [K+] gets into the cell is via...

Back 6

Na+/K+ ATPase

Front 7

With INORGANIC metabolic acidosis (HCO3- loss or HCl gain), H+ moves ___ of cells and K+ moves ___ cells.

Back 7

H+ moves INTO; K+ moves OUT

Note: There is little shift in organic acidosis

Front 8

In metabolic alkalosis, K+ moves ____ cells, and H+ moves ____ of cells.

Back 8

K+ moves INTO; H+ moves OUT

Note: There is little shift in respiratory alkalosis

Front 9

_______ are in charge of long-term potassium balance.

Back 9

Kidneys (through increase/decrease of excretion)

Front 10

Factors promoting K+ excretion

Back 10

- Aldosterone***
- Distal flow of Na and water (providing Na for exchangers)
- Plasma potassium concentration

Front 11

Virtually all regulation of K+ occurs in the _____.

Back 11

CCD (Cortical collecting duct)

Front 12

Events controlling K+ excretion have the greatest impact in the _____.

Back 12

CCD (Cortical collecting duct)

Front 13

hyper-_____ and hypo-_____ are two major stimuli for aldosterone release.

Back 13

Hyperkalemia; Hypovolemia

Front 14

Factors contributing to ACUTE hyperkalemia

Back 14

- Increased load
- Impaired excretion
- Release from cells (metabolic acidosis, cell lysis, rhabdomyolysis, beta blockade, insulin deficiency, exercise)

Front 15

Factors contributing to CHRONIC hyperkalemia

Back 15

- Severe renal failure
- Hypoaldosteronism
- Decreased distal flow and subsequent Na delivery
- Drugs (K-sparing diuretics, NSAIDs, ACE inhibitors, trimethoprim)

Front 16

T or F: A hyperkalemic patient usually has more than one reason for hyperkalemia

Back 16

TRUE

Front 17

Key questions in assessing the cause of a non-obvious case of hyper-/hypokalemia:

Back 17

1*** - Urine [K+] . . . (Normal is 80. If healthy kidney, hypokalemia excretion will be around 20, and hyperkalemia will be around 200)

2 - Is the problem in cortical
collecting duct volume or [K+]?

3*** - Is aldosterone acting? (TTKG = ((U/P) for K+) / ((U/P) for Osm) . . . TTKG > 7 means aldo is acting and TTKG < 2 means aldo is NOT acting.)

Front 18

Mechanism of K+ loss during vomiting

Back 18

K+ is lost via the URINE due to alkalosis, and increase aldosterone stimulation from hypovolemia.

Front 19

Correcting severe hypokalemia may need several hundred mmol of ___ given in the form of _____ unless the patient is acidemic.

Back 19

K+; KCl

Front 20

Licorice can cause an excess of ________ through the inhibition of _______.

Back 20

aldosterone; 11-Beta Hydroxysteroid Dehydrogenase

Front 21

Define primary hyperaldosteronism

Back 21

problems with the adrenal glands themselves producing too much aldosterone - either from a tumor, or some idiopathic etiology.

Front 22

Liddle syndrome

Back 22

aldosterone gain of function through a mutation, causing HTN, hypokalemia, and metabolic alkalosis. Treat with amiloride.

Front 23

Bartter and Gitelman Syndrome

Back 23

- Bartter: mimics loop diuretics, HYPERcalciuria ("Barter with my parents to go on the loop-de-loop roller coaster")

- Gitelman: mimics thiazide diuretics, HYPOcalciuria

- Bartter occurs earlier in life ("Bartters in babies"), and Gitelman is more common overall.

Front 24

All diuretics (except apironolactone) act on the ____-side of the nephron.

Back 24

LUMINAL-side

Front 25

All diuretics (except mannitol) get into the lumen via...

Back 25

SECRETION into the proximal tubule.

Front 26

Pharm: Mannitol

(MOA, Pharmacokinetics, Toxicity, Indications,Contraindications)

Back 26

1) Mechanism of action
-osmotic diuretic, acts as an osmole, pulling fluid into the tubule.

2) Pharmacokinetics
-only given intravenously, t1/2 ~1 hr

3) Toxicity
-from increased plasma osmolality

4)Indications
-decrease CNS pressure

5)Contraindications
-CHF, renal failure

Front 27

Pharm: Acetazolamide

(MOA, Pharmacokinetics, Toxicity, Indications,Contraindications)

Back 27

1) MOA
- increase urinary bicarb, K+, and water excretion. (Won't work unless there's adequate biarb in the plamsa.)

2) Pharmacokinetics
- weak diuretic, t1/2 ~ 13 hrs

3) Toxicity
- metabolic acidosis from losing bibarb and hypokalemia

4) Indications
- Glaucoma, CNS pressure, altitude sickness, urine alkalinization

5) contraindications
- liver failure

Front 28

Pharm: Loop diuretics (MOA)

Back 28

Mechanism of action: Inhibition of Na/K/2Cl co-transporters (AKA "furosemide-sensitive transporters")

Front 29

Pharm: Loop diuretics (Pharmacokinetics)

Back 29

Fast - acts in 20 minutes. Most potent of the diuretics. t1/2 ~ 1-2 hrs.

Front 30

Pharm: Loop diuretics (Toxicity)

Back 30

- hypokalemia
- volume contraction
- Ca and Mg depletion

Front 31

Pharm: Loop diuretics (Indications/Contraindications)

Back 31

Indication: HTN, acute diuresis needed, need more potent diuretic, hypercalcemia

Contraindication: susceptible to vomune depletion (i.e. the elderly), susceptible to hypokalemia (digitalis, hepatic cirrhosis)

Front 32

Pharm: Thiazide diuretics (MOA)

Back 32

Mechanism of action: inhibits NaCl transport in the cortical thick ascending loop and distal tubule

Front 33

Pharm: Thiazide diuretics (Pharmakokinetics)

Back 33

well absorbed from gut, acts within 1 hr, lasts 6-48 HOURS

Note: these last longer than loop diuretics, thus, they're more likely to cause hypokalemia

Front 34

Pharm: Thiazide diuretics (toxicity)

Back 34

hypokalemia, hyponatremia, hyperuricemia, and hypercalcemia

Front 35

Pharm: Metolazone

Back 35

same MOA as thiazides; given in addition to loop diuretics sometimes for extra "punch"; often given in more advanced renal insufficiency

Front 36

Pharm: K-Sparing Diuretics (MOA)

e.g. Spironolactone and Eplerenone

Back 36

MOA: competitive aldosterone antagonist. Inhibits the reabsorption of Na as well as K+/H+ secretion in the late distal tubule and collecting duct.

Front 37

Pharm: K-Sparing Diuretics (Pharmakokinetics)

e.g. Spironolactone and Eplerenone

Back 37

Takes up to 2 days to start working; spironolactone is the only diuretic to work on the "blood" side of the tubule; relatively weak diuretic

Front 38

Pharm: K-Sparing Diuretics (Toxicity)

e.g. Spironolactone and Eplerenone

Back 38

- Hyperkalemia
- Gynecomastia, and amenorrhea (spironolactone)

Front 39

Pharm: K-Sparing Diuretics (Indications/Contraindications)

e.g. Spironolactone and Eplerenone

Back 39

Indications: Primary hyperaldosteronism, Secondary hyperaldosteronism (cirrhosis), Chronic heart failure (reduces mortality)

Contraindications: hyperkalemia

Front 40

Pharm: amiloride (MOA)

Back 40

K+ sparing diuretic (so don't give to a hyperkalemic patient), inhibits the Na+ channels in the late tubule and collecting duct, and since the positively-charge Na isn't reabsorbed, the positively-charge K+ doesn't move out into the lumen to take its place, thus, it's potassium-sparing.

Front 41

Why don't diuretics work?

Back 41

- failure to treat the underlying/primary disorder
- high Na intake
- noncompliance
- volume depletion
- NSAIDs (reducing renal blood flow)
- metabolic acidosis (lowers efficacy of carbonic anhydrase inhibitors)

Front 42

The two main substances the kidney uses to "deal with" (excrete) acids

Back 42

Ammonia (binds a H+ to turn into ammonium), Phosphate

Front 43

How to use urinary Cl- to treat metabolic alkalosis

Back 43

Urinary Cl- is < 10 = chloride RESPONSIVE = non-renal problem . . . give NaCl

Urinary Cl- is > 10 = chloride UNresponsive = kidney's fault . . . stop diuretics, and treat the problem.

Front 44

Most important test to help you determine the cause of non-anion gap metabolic acidosis is:

Back 44

Urinary anion gap
= urinary (Na + K) - Cl