What’s being “measured” or sensed in osmoregulation? And in volume regulation?
Osmoregulation: plasma osmolality
V reg: effective circulating volume
What are the sensors for osmoregulation? And for volume regulation?
Osmoregulation: hypothalamic osmoreceptors
V reg: Carotid sinus, JG cells (afferent arteriole), atria
What are the effectors for osmoregulation? And for volume regulation?
Osmo: ADH
V reg: RAAS, SNS, ADH, natriuretic peptides
In osmoregulation, (X) intake/excretion is affected. And in volume regulation?
X = water
V reg: Na
Hypovolemia is loss of (X) from which compartments? Serum osmolality (increases/decreases/same).
X = Na and water
ECF
No change (reduced TBW and TBNa)
Dehydration is loss of (X) from which compartments? Serum osmolality (increases/decreases/same).
X = water
ECF and ICF
Increases (reduction in TBW, so hypernatremia)
Total body sodium content is proportional to (X) volume.
X = ECF (circulating volume)
T/F: normally, nearly all Na excretion is in the urine.
True
Excessive vomiting/diarrhea will result in (Na/H2O) loss.
Both, but moreso water (hypo-osmotic fluids lost)
How many days of deficient Na intake will result in salt depletion?
Deficient intake alone won’t result in Na depletion! Urine Na excretion will drop
Salt depletion occurs by one of which two mechanisms?
- Extra-renal (GI, sweat)
2. Renal/adrenal (tubular disease, adrenal insufficiency)
Measuring (X) can help distinguish between renal and extra-renal Na depletion.
X = urine Na conc
Will be less than 10 mEq/L if extra-renal
List some clinical findings that suggest Na depletion.
- Low turgor
- Postural hypotension
- Decreased BW
- Increased HCT
T/F: In edematous state, all body volumes are high.
False - low effective circulating V
Hyponatremia: (X) is decreased by definition. You should ask yourself “why doesn’t the patient (Y)?”
X = serum Na conc (imbalance with excess water relative to Na)
Y = secrete water normally
List 5 causes for hyponatremia
- ECF depletion
- ECF excess
- Euvolemia
- Endocrine
- Drug
Edema and low urine Na are clinical hallmarks of (hyper/hypo)-natremia, secondary to (X) syndrome/cause.
Hyponatremia;
X = ECF excess (CHF, cirrhosis)
Measuring (X) will be valuable in determining if cause of (hyper/hypo)-natremia is due to Diabetes Insipidus. What do you expect (X) to be in DI?
X = urine Osm
Hypernatremia
Lower than serum Osm
Decreased effective circulating volume (ECV) occurs in (hypo/hyper)-volemic states.
Both
(X) is an indirect measure of ADH
X = urine Osm
Key concepts: (X) reflects TBW and (Y) reflects TBNa
X = serum Na Y = volume status
Normal serum Osm
280-310 mOsm/kg
Hyponatremia is serum (X) lower than which value?
X = Na conc
135 mM
(Note: under 120 mM is danger zone)
How do you treat patient who is hyponatremic with isotonic serum Osm?
Do nothing - treat underlying cause
normal serum Osm means body likely producing molecule like Ig that is interfering with measurement
Why might patient with uncontrolled diabetes mellitus present with hyponatremia?
Hypertonic hyponatremia (hyperglycemia may be causing water exit from cells, thereby diluting serum Na)
Patient with mineralocorticoid deficiency will likely present with (hyper/hypo/eh)-volemic hyponatremia and should be treated with (X).
Hypovolemic
IV saline (isotonic)
List some causes of hypovolemic hyponatremia.
Renal: diuretics, Na wasting nephropathy, mineralocorticoid deficiency
Extra-renal: GI/skin losses
List two main classes of drugs that can cause SIADH and (hyper/hypo/eh)-volemic hyponatremia.
Euvolemic
Antidepressants and antipsychotics
SIADH: Urine Osm (higher/lower/same) compared to serum Osm.
Higher (over 300) - water can’t get out of body!
Tea and toast diet leads to (hyper/hypo/eu)-volemic hyponatremia because there is too (much/little) (X) in diet.
Euvolemic hyponatremia
Too little
X = solute
How would you treat patient with hyponatremia secondary to SIADH?
Euvolemic hyponatremia; restrict water and liberalize dietary Na
Consider hypertonic saline
T/F: Hypernatremia is always a hyperosmolar state (high serum Osm).
True
Rate of Na correction in hyponatremic state: under (X) over first 24 hours and under (Y) over first 48 hours.
X = 6-10 mEq/L Y = 18 mEq/L
List the three mechanisms the kidneys use to handle an acid load.
- Recycle H+ to reabsorb bicarb
- Titratable acid secretion (to bind H+)
- Excrete NH4+
List the locations along the nephron that NH4+ is secreted
Proximal tubule, ALOH, and collecting ducts
You would expect VBG to have higher (pH/pCO2/HCO3/O2) relative to ABG. Which value(s) should not be estimated from VBG (difference is too big).
pCO2 and HCO3
Don’t estimate O2 from VBG
Anion gap must be corrected for if patient has too (high/low) (X) in blood. Why and how is this accounted for?
Low
X = albumin
It’s a major unmeasured anion that constitutes the Gap, so must be accounted for if low levels
Every 1g/dL drop in albumin decreases anion gap by 2.5
List differential for metabolic acidosis with anion gap
MUDPILES
- Methanol
- Uremia
- DKA
- Pyroglutamic acidosis, propylene glycol
- INH overdose
- Lactic acidosis
- Ethanol, ethylene glycol
- Salicylates, starvation ketoacidosis
Anion gap over 20 is red flag to calculate (X). What’s the formula?
X = Osm gap
Expected serum Osm - measured serum Osm
Normal Osm gap is:
10-15
Serum Osm calculated with which equation?
2(Na) + (Glucose/18) + (BUN/2.8) + (EtOH/4.6)
Anion gap is 25 so you calculate (X) and it’s also 25. You have high suspicion for (Y) as the cause for metabolic acidosis.
X = Osm gap Y = intoxication by ethylene glycol, methanol, or propylene glycol
Patient with metabolic acidosis has anion gap of 18. How do you figure out if another metabolic disorder is present?
Delta gap calculation:
= 24 means just AGMA
Under 24 means AGMA + non-gap acidosis
Over 24 means AGMA + metabolic alkalosis
Patient with metabolic acidosis has anion gap of 18. How do you figure out if there is additional respiratory disorder present?
Winter’s formula:
Expected pCO2 = (1.5)(HCO3) + 8
Range is plus/minus value calculated
Differential for non-gap metabolic acidosis
RUN-DIC
- RTA
- Uremia
- NaCl (large V of isotonic saline)
- Diarrhea
- Intestinal-bladder fistula
- Carbonic Anhydrase Inhibitors
What’s the problem in proximal RTA (Renal Tubular Acidosis) Type 2?
Decreased ability for proximal tubule to reabsorb HCO3
What’s the problem in distal RTA (Renal Tubular Acidosis) Type 1?
Unable to acidify urine
Unknown but likely decrease in H+ secretion or diffusion back into cell
What’s the problem in distal RTA (Renal Tubular Acidosis) Type 4?
Hyporeninemia, hypoaldosteronemia, OR aldosterone insensitivity
DKA: patients are volume (overloaded/depleted) as a result of (X). Despite their (low/high) total body K, their serum K concentration is (low/high).
Depleted
X = hyperglycemia (glucose in urine acts as diuretic)
Super low TBK, but high extracellular conc (acidemia pulls K out of cells in exchange for H)
Treatment of DKA
Insulin and saline (replace K, Na, and water)
Note: if pH super low, bicarbonate admin too
What’s your differential for patient presenting with DKA symptoms but normal blood glucose?
Starvation or alcoholic ketoacidosis
Patient with (gap/nongap) metabolic acidosis has oxylate crystals in urine, so you know the cause is:
Gap
Ethylene glycol ingestion
Distal RTAs (Type 1 and 4) can be distinguished by serum measurement of (X).
X = K
Type 1 (hypokalemic) Type 4 (hyperkalemic - aldosterone issues)
T/F: Proximal RTA (Type 2) has normal serum K.
True (or on the low side)
A serum bicarbonate under 10 would make you suspect which RTA?
Type 1 (distal, hypokalemic)
A serum bicarbonate over 15 would make you suspect which RTA?
Could be Type 2 (proximal) or Type 4 (distal hyperkalemic)
A serum bicarbonate over 20 would make you suspect which RTA?
Type 4 (distal hyperkalemic)
List some causes for acquired Type 1 (distal hypokalemic) RTA
- Sjogren’s
- Hyperparathyroidism
- Amphotericin B
List some causes for acquired Type 2 (proximal) RTA
- Multiple myeloma
- Acetazolamide
- Heavy metals
Urine anion gap equation:
(Na+K) - (Cl)
Patient has non-gap MA and you decide to calculate (X) to figure out if RTA is the cause.
X = urine anion gap
If positive, tubules not working (too little NH4Cl around)
List examples of Cl-sensitive metabolic alkalosis etiologies
- Vomit/Gastric drainage
- Diuretics
- Relief of chronic hypercapnia
List examples of Cl-insensitive metabolic alkalosis etiologies
- Cushing
- Conn’s (1o aldosteronism)
- Bartter’s
In order to “maintain” metabolic alkalosis, (X) becomes a key player in stimulating kidney to detrimentally continue bicarbonate reabsorption.
X = aldosterone
V depletion stimulates RAAS and aldosterone stimulates Na reabsorption (along with anions such as bicarb)
Chronic metabolic alkalosis will present with (hyper/hypo)-kalemia.
Hypokalemia (remember aldosterone key player in maintaining this alkalosis)
Chronic metabolic alkalosis: urine pH (low/high), and what about Na, K, Cl values?
Low (paradoxically);
K is high; Na and Cl at minimum values
How do diuretics cause Cl-sensitive metabolic alkalosis?
Similar to vomiting, secreting of H+ in excess amounts in urine Leads to volume depletion and aldosterone secretion
T/F: in Cl insensitive metabolic alkalosis, patients are V overloaded.
True (may be hypertensive)
Key corrective maneuvers that should be taken to correct acute metabolic alkalosis
- Restore IV volume
- Replete K (to upper limit of normal)
Also monitor pCO2 and pO2 carefully
T/F: Urine is hypotonic to your blood.
True
Post-obstructive renal failure patients produce liters of urine once catheter is in. What are the main driving forces for all this urine production?
- Lots of urine build up from obstruction
2. Urea (build up in blood) acts as diuretic
Carpal spasm occurs in the setting of (X) acid-base disorder. What’s the mechanism behind this?
X = respiratory alkalosis
Increase pH decreases ionized Ca and induces muscle spasm
T/F: Serum Ca falls during respiratory alkalosis, leading to carpal spasm.
False - serum levels unchanged
Management of acute respiratory alkalosis.
Breathe into closed system and manage underlying disorder (if any)
Your patient with stage 4 CKD likely has (gap/non-gap) metabolic acidosis.
High anion Gap (retention of phosphates, sulfates, and organic acids that make up anion gap)
Your patient with stage 3 CKD likely has (gap/non-gap) metabolic acidosis.
Non-gap (reduced ability to generate ammonia)