Disorders of Fluid and Plasma K Flashcards
What is the typical level of total body K?
What is the distribution among body cavities?
50mEq/kg so roughly 3500mEq
It is 98% intracellular and 2% extracellular
What are the 2 major modes of excretion of K from the body? Which is more important?
- Renal - excretes 90%
2. GI- excretes 10%
Describe the normal filtration/reabsorption/secretion of K through the nephron.
K+ is freely filtered by the glomerulus
- extensive reabsorption in the proximal tubule
- distal nephron secretes K into tubular fluid (which determines how much K is excreted by the kidney)
What is the pathophysiology of the CCD that determines how much K will be secreted?
Describe the transcellular and paracellular pathways
Transcellular:
Na/K pump on the basolateral membrane increases K concentration intracellularly.
This creates a large gradient for K between the cell and tubular lumen.
There is a ROMK channel on the apical membrane that allows K to enter the lumen.
Electropotential of the lumen is slightly + compare to the cell so it inhibits passive movement of K across the luminal membrane, but the concentration gradient is large enough to overcome
Paracellular:
The lumen is 50mV negative compared to the blood so it drives K
What are the 4 cellular determinants for K secretion?
- Cell K concentration
- luminal K concentration
- Potential difference across luminal membrane
- permeability of luminal membrane for K
What are the 2 main physiological determinants for K secretion?
- Mineralocorticoids
2. Distal delivery of Na and nonreabsorbable anions
What is the major mineralocorticoid involved in regulation of K?
What are the 2 things that cause its release?
Aldosterone is secreted from the zona glomerulosa of the adrenal gland in response to:
- hyperkalemia
- Ang II (dependent on renin release)
What are the 2 main effects of aldosterone on the CCD?
- increase Na reabsorption through the luminal channel
- increases the excretion of K because it increases intracellular K and increases the gradient (in addition to making lumen more negative)
What is the effect of aldosterone on acid base balance?
It increases the excretion of H+ from intercalated cells in the CCD
This acidifies the urine, and makes the ECF more basic
How does distal Na delivery regulate K?
Increased distal delivery of Na stimulates distal Na reabsorption which makes the lumen more negative, increasing K secretion.
How does flow rate effect K secretion?
High flow rates, the same amount of K secretion is diluted by a larger volume so the rise in K concentration is smaller. This allows more K to be secreted
How do nonreasborbable anions affect K secretion?
What are examples of nonreabsorbable anions?
Since non-reabsorbable anions are not reabsorbed in the proximal tubule, they increase distal delivery of Na and increased volume
They also increase the lumen’s negative potential .
This secondary increases excretion of K .
Ex. sulfate, phosphate, carbenicillin, HCO3
Why is K excretion independent of volume status?
If volume is contracted, there will be decreased distal delivery, but increased aldosterone.
If volume is increased, there will be increased distal delivery, but decreased aldo, so they keep each other in check
If there is primary mineralocorticoid excess, what happens to:
- level of mineralocorticoid
- distal delivery
- UkV
- increased
- increased
- increased
If there is a primary increase in distal delivery, what happens to:
- level of mineralocorticoid
- distal delivery
- UkV
- increased
- increased
- increased
What are the 4 main conditions that cause abnormalities in K secretion?
Give one example of a cause for each.
Which cause hypo and which cause hyperkalemia?
Hypokalemia:
- primary mineralocorticoid excess - aldosterone secreting tumor
- primary increase of distal delivery- diuretic
Hyperkalemia:
- primary mineralocorticoid decrease- Addison’s/adrenal gland destruction
- primary decrease in distal delivery- acute oliguric renal failure (decreased urine output)
What are the 4 physiologic determinants of K untake by cells?
- insulin - prevents hyperkalemia after a meal
- B-agonists -prevent hyperkalemia in exercise
- plasma K
What are the 5 pathologic causes that determine K uptake into cells?
- alkalosis
- cell death
- hyperosmolarity
- succinylcholine
- periodic paralysis
How many mEq K classifies hypokalemia?
> 200 mEq
What are the 4 categories of hypokalemia?
- decreased K intake - unlikely
- GI loss- diarrhea OR vomiting
- Renal loss
- cellular redistribution
What are the 3 major ways by which renal loss can lead to hypokalemia?
- Primary mineralocorticoid excess
- Primary increased distal delivery
- Primary increase in distal non-reabsorbable anions
What are the 4 major types of primary mineralocorticoid excess? Give examples for each?
- Primary hyperaldosteronism
- Conn’s
- BAH - Primary hyperreninism
- renin secreting tumor
- renovascular hypertension, accelerated hypertension - Non-aldosterone Mineralocorticoids
- Cushing’s syndrome - Hypokalemia and hypertension
- Liddle syndrome (ENaC mutation)
What are 5 potential causes for increased distal delivery that can lead to renal loss of K?
- Diuretics
- Osmotic diuretics (glucose, mannitol, etc)
- Bartter’s syndrome
- Gitelman’s syndrome
- Mg deficiency
What are the 5 major causes for increased distal delivery of non-reabsorbable anions?
- penicillin
- Ketoacids
- Metabolic alkalosis (vomiting)
- proximal RTA
- Acetazolamide
If a patient comes to see you and they have hypokalemia, but their urinary K is <20mEq/day, what is the most likely cause?
Diarrhea
A patient has hypokalemia and the urinary K is >20mEq/day. They have normal BP/EABV, What is the likely problem?
A primary problem with aldosterone or renin,
If R and A are increased, there may be a renin secreting tumor, or renal artery stenosis
If R is low and A is high, they may have Conn’s syndrome of BAH or GC suppressible hyperaldosteronism
If R and A are both low, they may have Liddle syndrome (a mutation of ENaC) or Cushings (non-aldosterone mineralocorticoid that can still activate MR in the CCD)
A patient has hypokalemia and urinary K is >20mEq/day. They have low BP/EABV. You check the serum HCO3 and note that is is low. What is the likely cause of the problem?
RTA
A patient has hypokalemia and urinary K is >20. They have low BP/EABV. They have high serum HCO3, so you check the urine Cl. It is low. What is the likely problem?
The low Cl- means that is is still being reasborbed, however, the K is still low which indicates that the increased distal delivery is due to non-reabsorbable anions from:
- vomiting (increased HCO3)
- penicillin (carbenicillin)
- ketoacidosis (alcohol, diabetes, starvation)
- acetazolamide (CA inhibitor)
A patient presents with hypokalemia and urinary K is >20. They have low BP/EABV. The serum HCO3 is high. Urine Cl is also high.
What is the likely problem?
All the signs point to increased distal delivery so the likely causes are:
- diuretics
- Bartter’s
- Gittelman’s
- Mg deficiency
- osmotic diuretics
If a patient stops eating Na, the fecal and renal loss will drop to almost zero.
For K, the renal excretion cannot drop below ____ and fecal cannot drop below ______.
This means if a person gets less than _______ of K a day, they may become hypokalemic.
renal cannot drop below 5mEq/day
GI cannot drop below 5-10mEq/day
People need 10-15mEq a day
What is the mechanism by which vomiting can cause hypokalemia?
If the vomit itself caused hypokalemia, that would mean the patient would have to vomit 20L .
The actual mechanism is that vomiting leads to metabolic alkalosis (increased HCO3) which is a non-reabsorbable anion. This leads to renal K wasting.
Also, alkalosis drives K into cells in exchange for H which furthers the hypokalemia
Why does diarrhea cause hypokalemia that does not accurately reflect the severity of the K loss?
The diarrhea leads to marked fecal K wasting.
It also causes acidosis.
The acidosis causes K to exchange for H where H goes into cells and K comes out. This makes the hypokalemia seem less severe
A defect in what enzyme can lead to cortisol excess and subsequent hypertension/ hypokalemia/metabolic alkalosis?
11B-OSHDH2
There are genetic mutations in this enzyme, but also licorice can inactivate it
What is the mechanism by which Bartter’s syndrome causes hypokalemia?
It is a genetic disorder that affects Na/K/2Cl cotransporter in the loop of Henle. This decreases salt absorption by the same mechanism of a loop diuretic and leads to hypokalemia.
What is the mechanism by which Gitelman’s syndrome cause hypokalemia?
It acts in the DCT and blocks NaCl reabsorption which increased distal delivery of Na to the CCD and leads to K wasting in a similar mechanism to Thiazide.
The two most common causes of hypokalemia are GI and renal loss. What question in the history can you ask to determine which is occurring?
What can be done if you do not trust the patients answer?
Have you been vomiting or having diarrhea?
If the patient is a laxative abuser, they might not give a truthful answer. In this instance, order a 24 hour urine for K.
If K is
What is the order of tests that should be performed to determine the cause of hypokalemia?
- History
- Urine K (and if above 20mEq continue)
- BP/EABV
- if low, suggestive of primary increase of distal delivery
- if normal/high, suggestive of mineralocorticoid excess - If suspected mineralocorticoid problem, test renin/aldosterone levels
What are the 4 major causes of hyperkalemia?
- pseudohyperkalemia (trauma on venopuncture, or increased WBC/platelets)
- excessive intake
- decreased renal excretion
- cellular redistribution
What is pseudohyperkalemia?
If there is:
- trauma/cell injury to cause K leak
- increased platelet or WBC
- clotting prior to centrifuge
It can give a false reading of hyperkalemia.
Confirm by re-measuring serum K in a blood sample collected with heparin
Decreased renal K excretion falls into what 3 categories?
- decreased distal delivery
- primary mineralocorticoid deficiency
- distal tubular defect
What are the 2 major causes of decreased distal delivery leading to hyperkalemia?
- acute oliguric renal failure (decreased GFR which decreased distal delivery)
- chonic renal failure
What are the 4 major causes of decreased mineralocorticoid that leads to decreased renal K excretion?
.1. Addison’s
- hyporeninemic hypoaldosteronism
- ACEI
- adrenal biosynthetic defects
What are the 2 major distal tubular defects that can lead to hyperkalemia?
- spironolactone, triamterene, amiloride
2. intrinsic renal disease
How does CKD cause hyperkalemia?
What are 2 defenses people with CKD have against hyperkalemia?
- decreased distal delivery because of the reduced GFR (hyperkalemia doesnt present until GFR <5)
- nephron drop-out so less CCD to secrete K
Defenses:
- take K into cells faster than most people
- increased K excretion in stool
A patient has a GFR of 11. Their bloodwork shows decreased renin and aldosterone. They have hyperkalemia. What is the likely problem?
Hyporeninemic hypoaldosteronism due to CKD, specifically:
- diabetic nephropathy
- interstitial renal disease
How do amiloride and triamterene differ from spironolactone?
A and T inhibit the Na channel in CCD making the lumen more positive and decreasing K excretion.
S blocks the MR via competitive antagonism to aldosterone
What is the most important cause of hyperkalemia due to redistribution of K out of the cell?
Tissue injury - rhabdo, trauma, burns, tumor lysis, massive IVC
Why are diabetics more prone to hyperkalemia?
If they have a sudden increase in plasma glucose, the increase in osmolarity will move K out of the cell as a result of solute drag with the water
How does succinylcholine cause K to leave the cell?
It depolarizes the cell membrane and causes K to leave
Organic acids themselves are not sufficient to shift K out of cells to cause hyperkalemia, so why is it that they are sometimes associated with hyperkalemia?
Diabetic ketoacidosis has an insulin insufficiency (insulin usually shifts K into cells)
Lactic acidosis is associated with cell injury and the release of K out of muscle cells
They both increase osmolarity which can shift K
What are the two main causes of ICU hyperkalemia?
What are the 2 main causes of office hyperkalemia<
ICU-
- cell shift
- acute renal failure
Office-
- decreased mineralocorticoids
- abnormal CCD
What is the clinical presentation of someone with hypokalemia?
(muscular, cardiac, renal, other)
- neuromuscular
- weakness
- rhabdomyolysis - cardiac arrythmia
- renal
- concentration defects
- metabolic alkalosis - glucose intolerance
What does the EKG show for someone with hypokalemia?
ST depression
T wave flattening
increased U wave
What are the effects of hypokalemia on the kidneys?
- it decreases the medullary gradient and causes resistance of CCD to ADH –> concentrating defect and polyuria, polydypsia
- metabolic alkalosis
What are the effects of hyperkalemia on the heart?
What does the EKG show for mild, moderate, severe, and fatal hyperkalemia?
It leads to depolarization resetting the threshold and causing depolarization block
Mild: peaked T
Moderate : peaked T and QRS,PR widens
Severe: sine waves
Fatal- flat line
What is treatment of hyperkalemia based on?
What are the 5 steps of treatment?
The EKG appearance NOT the total K level
- CaCl IV
- NaHCO3
- glucose/insulin
- albuterol
- dialysis/ K binding resin
