Tonicity and Volume

Question 1

models to explain inner medulla capacity to create osmotic gradient (3)

Answer 1

countercurrent multiplier model works for outer medulla and inner cortex (relies on active transport in TAL), but not inner medulla - for inner medulla, need a different model: either passive permeability (favored), metabolic, or physico-mechanism model; passive permeability model: urea actively tx CD -> interstitium, desc limb equilibrates by losing water to hypertonic interstitium and thus incr Na concentration in tubule, ascending limb is now hypertonic and thus loses solute to interstitium (making interstitium more concentrated), TAL adds even more solute to interstitium thru active transport; metabolic model: anaerobic glycolysis in inner medulla (due to low O2) creates lactate -> hypertonic interstitium; physico-mechanism model: medulla is like a gel, and as it is squeezed, water leaves without solute leaving -> hypertonic interstitium

Question 2

max concentrating ability: how to collect, what is normal

Answer 2

collect after 12 hrs of fasting or when pt has high plasma osmolarity; normal is Uosm > 800 mOsm/kg (max is 1200, but requires several days to reach that); we often use 500 as a cut off in hypertonic patients because they are often malnourished and may be on diuretics (but if Uosm >500, then ADH is working normally to attempt to fix hypertonicity)

Question 3

calculating free water excretion

Answer 3

urine volume = Cosm + Cwater; Cosm = UosmV/Posm; we can do the same for electrolyte-free water using Una+k and Pna

Question 4

Posm calculation vs Ptonicity calculation; estimated Posm calculation vs estimated Ptonicity equation

Answer 4

Posm = 2Na + glucose/18 + BUN/2.8; Ptonicity = 2Na + glucose/18; estimated Posm = 2Na + 10; estimated Ptonicity = 2Na + 5

Question 5

hepatic cirrhosis causes hypervolemia - theories (2), tx (3)

Answer 5

underfilling theory: splanchnic vasodilation and AV fistulas lead to decr SVR -> decr BP -> decr ECV -> RAAS -> Na retention -> ascites/edema, edema can also be due to hypoalbuminemia (decr synthetic fn); overflow hypothesis: primary Na retention occurs independent of other hemodynamic changes; tx w/ Na restriction, diuretics (spironolactone preferred due to incr RAAS in cirrhosis), poss paracentesis

Question 6

mech of edema in nephrotic syndrome - 2 theories, tx (2)

Answer 6

underfill hypothesis: proteinuria -> hypoalbuminemia -> reduced oncotic P -> ECF enters interstitium -> decr ECV -> RAAS -> Na retention -> edema; overfill hypothesis (favored): primary renal Na retention is secondary to underlying kidney disease (not due to proteinuria), poss due to selective incr in Na reabs in CD due to incr NK pump activity and resistance to ANP (due to incr PDE activity); pts respond well to diuretics and Na restriction, and thus overfill hypothesis is likely (if underfill was likely, then Na restriction would decr ECV more and worsen problem)

Question 7

hyponatremia frequency

Answer 7

15-20%

Question 8

brain compensation for hyponatremia

Answer 8

prevents swelling by acutely increasing CSF outflow, then by extruding K (takes 3-4 hrs, max in under a day) and small organic solutes like AAs (takes several days); thus if hypotonicity is corrected too quickly after the fact, brain cells will shrink due to reduced solute concentration

Question 9

general causes of hypotonicity (2)

Answer 9

kidney hypoperfusion (incr PT water reabs via renin -> if EABV is low, only 1.5 L/day delivered distally for possible excretion); high ADH (impairs CD water excretion)

Question 10

how much water can a healthy kidney clear in a day if ADH is low and EABV is normal?

Answer 10

18 L

Question 11

hyponatremia and hypernatremia vs hypotonicity vs hypertonicity

Answer 11

hyponatremia can exist w/ hypertonicity (i.e. hyperglycemia) or hypotonicity; hypernatremia only exists w/ hypertonicity

Question 12

hyponatremia patient evaluation

Answer 12

if Uosm is 100 (concentrated urine), then check V status. If hypovolemia, then due to renal or extrarenal Na loss (slightly more Na lost than water lost -> hyponatremia); if euvolemia, then due to renal loss of pure water via SIAD, thiazides, cortisol deficiency, hypothyroid; if hypervolemic, then due to CHF or cirrhosis (gain of hypotonic fluid)

Question 13

hypovolemic hypotonic hyponatremia general cause (2), diff dx (7)

Answer 13

V depletion means low TBW means low TBNa, hyponatremia means more water than Na, thus both Na and water lost but a little more Na than water (hypertonic fluid deficit); this can occur after extreme volume loss stimulates ADH despite hypotonicity; loss can be renal: diuretics, renal failure, adrenal insufficiency (hypoaldo), vomiting/NG suction (-> alkalemia -> urinary NaHCO3 loss); or loss can be extrarenal: diarrhea, profuse sweating, extensive burns, vomiting/NG suction

Question 14

euvolemic hypotonic hyponatremia general cause, diff dx (4)

Answer 14

V w/in 10% of normal therefore TBNa relatively normal and biggest problem is excess pure free water; water can be retained in kidney: SIADH (subclinically hypervolemic), thiazides (subclincially hypovolemic -> ADH release), cortisol deficiency (cortisol inhibits ADH release), hypothyroid (TH inhibits ADH and increases heart contractility -> w/ low TH, high ADH and decr EABV)

Question 15

causes of SIADH (4)

Answer 15

small cell lung carcinoma; drugs; pneumonia and other pulm processes; genetics (V2 mutation)

Question 16

differentiating euvolemic hyponatremia due to SIADH vs thiazides

Answer 16

SIADH = subclinically hypervolemic = high uric acid excretion = low uric acid in serum; thiazide = subclinically hypovolemic = low uric acid excretion = high uric acid in serum

Question 17

hypervolemic hypotonic hyponatremia diff dx (3), general cause

Answer 17

CHF (poor pump therefore poor renal perfusion), liver disease (AV shunting from estrogen, so poor renal perfusion), nephrosis (low oncotic P so edema so low BP so poor renal perfusion, also proteinuria makes generating a dilute urine difficult) -> all of these cause low EABV and thus high ADH (hypotonic fluid excess)

Question 18

sx of hyponatremic (4 sx, Na levels)

Answer 18

depends on magnitude and timeline: if acute, see sx at Na < 125 and coma/seizures < 115, if chronic, then don’t see sx until < 115; sx are mainly CNS: headache, muscle twitching, seizures, coma

Question 19

tx for hyponatremia (general tx, by type, what if dangerously low)

Answer 19

water restriction will ALWAYS improve hyponatremia (need water intake to be hyponatremic), but be careful if pt hypovolemic; if hypovolemic, give saline; if euvolemic, correct underlying disorder, restrict water intake, give vaptans to block ADH; if hypervolemic, tx underlying disorder, restrict water, give diuretics, ACEI, and vaptans; for severe sx (seizures/coma) give hypertonic Na (but be careful not to correct TOO quickly! Bring up to 120 acutely and then slowly correct to 130 mEq at <.5 mEq/hr)

Question 20

vaptans use, efficacy

Answer 20

inhibit ADH; use for pts w/ euvolemic and hypervolemic hyponatremia; fixes the numbers (Pna) but doesn’t fix sx -> maybe the hyponatremia isn’t the issue

Question 21

central pontine myelinolysis

Answer 21

aka osmotic demyelination due to rapid correction of hyponatremia (occurs 48 hrs post-insult) -> poss due to neuron shrinkage

Question 22

hypertonicity sx (2 sx classes, det by)

Answer 22

non-specific CNS: agitation, restlessness, confusion, lethargy -> seizures, coma; intracranial hemorrhage (particularly in infants due to fragile blood vessels); severity of sx det by age (v young and v old do poorly), magnitude of hypertonicity, timeline of hypertonicity dev.

Question 23

brain compensation for hypertonicity: hypernatremia vs hyperglycemia

Answer 23

hypernatremia takes brain 1 week to restore V via incr intracellular supply of idiogenic osmoles like Na and AA; hyperglycemia takes brain 4-6 hrs to restore V via incr intracellular supply of Na and possibly other unknown solutes

Question 24

euvolemic hypernatremia general cause, diff dx (3), how to differentiate

Answer 24

lose electrolyte-free water PLUS inadequate water intake; due to insensible water losses (skin or lungs), renal water losses (DI), and primary hypodipsia; differentiate by Uosm: if Uosm high (>500 or Uosm/Posm&raquo_space; 1), then kidney part of the solution (insensible water losses or hypodipsia); if Uosm low (< 1), then kidney part of the problem (DI)

Question 25

hypovolemic hypernatremia general cause, diff dx (9), how to differentiate

Answer 25

lose hypotonic fluid (dilute urine) - loss of Na leads to hypovolemia + loss of water in excess of Na leads to hypernatremia (hypotonic fluid loss) + inadequate water intake exacerbates problem; renal loss due to diuretics (esp thiazides), osmotic diuresis (glucose in DM, urea in post-obstructive diuresis and high protein tube feedings), Addisons (hypoaldo); GI loss due to diarrhea, vomiting/NG tube; cutaneous losses due to profuse sweating (marathon -> contains Na/K), extensive burns; differentiate w/ Uosm and Una: renal losses have low Uosm (20) in high V of urine, whereas extrarenal losses have high Uosm (>500) and low Una (<10) in low V of urine

Question 26

hypervolemic hypernatremia general cause, diff dx (5), complications (2)

Answer 26

gain hypertonic fluid (us. iatrogenic or in error); 5% NaHCO3 after MI, hypertonic (3-5%) NaCl to correct hyponatremia, 20% NaCl accidentally during abortion, salt poisoning in infant formula, sea water ingestion; leads to ECF expansion -> pulm edema, as well as ICF contraction -> neuro probs = life threatening emergency

Question 27

tx for hypernatremia (general tx, by type)

Answer 27

all hypernatremia can only occur w/ inadequate water intake, so giving water or D5W will fix hypernatremia (altho may want to avoid in hypervolemic hypernatremia) - give slowly to prevent cerebral edema; hypovolemic: give saline quickly to restore V, then water slowly to fix Na; euvolemic: give water/D5W slowly to prevent cerebral edema; hypervolemic: stabilize ventilation by treating pulm edema w diuretics and/or extracorpreal ultrafiltration if renal fn compromised as well as artificial ventilation, then correct Na w/ D5W after we correct V

Question 28

TBW: calculations, why it varies in diff ppl as % of weight

Answer 28

.6mass in men, .5mass in women; higher in infants and kids (65-75% weight) and decr w/ age; fat cells have less water than muscle, so more fat = lower TBW % of weight (aka women have lower TBW % of weight than men due to excess fat)

Question 29

calculating free water deficit

Answer 29

TBWnormal x Pna normal (140) = TBWpresent x Pna present; solve for TBWnormal and water deficit is TBWnormal - TBWpresent

Question 30

hyperosmolar hyperglycemic non-ketosis: pt pop (4), labs (2), phases (3), tx

Answer 30

older patients w/ prolonged polyuria and secondary polydipsia, may have no hx of diabetes, us. has precipitating factor (infx, steroids, diuretics, burns, dialysis, hyperalimentation, etc.); lab: severe hyperglycemia (>500), no ketosis b/c enough insulin present to prevent ketosis but not to prevent hyperglycemia; occurs in three phases: phase 1 = hyperglycemia = hypertonicity, ICF contraction, ECF expansion, hyponatremia (b/c ECF V incr); phase 2 = osmotic diuresis (hypotonic losses -> both ICF and ECF lose water) = hypertonicity, ICF contraction, ECF V variable, PNa variable; phase 3 = continued Na and water depletion (only ECF loses fluid) = hypertonicity, ICF contraction, ECF contraction due to Na loss, hypernatremia; DON’T TX WITH INSULIN (will drive glucose into cells and make ECF contraction worse -> glucose is the only thing maintaining the ECF volume), instead tx w/ isotonic saline to restore V (will help tx hyperglycemia itself as kidney excretes glucose) and then give low dose insulin slowly to prevent ECF contraction and edema, correct water deficits slowly to prevent cerebral edema

Question 31

estimating water deficits in hyperglycemia

Answer 31

Pna is predictably lower by hyperglycemia (Pna decreases 2.4 mEq/L for every 100 mg/dL increase in Pglucose), so use corrected Pna when calculating water deficits (hyperglycemia masks severity of V depletion b/c water is redistributed from ICF to ECF)

Question 32

relative ion concentrations in ICF and ECF (K, Na, Cl, protein, glucose, Ca, H, Pi) - main cations and anions in each compartment

Answer 32

K greater in ICF, Na greater in ECF, Cl greater in ECF, protein greater in ICF, glucose greater in ECF, Ca greater in ECF, H greater in ECF, bicarb greater in ECF, Pi greater in ICF; total osm in both still = 290; overall, ICF is mostly Na cation and protein/phosphate anion, and ECF is mostly K cation and chloride/bicarb anion