Week 7: BMP (not done) Flashcards
1) What is BMP also called? How many tests?
2) List the tests
3) What is the test that’s freq. included?
1) AKA BMP, chem 7, or chemistry panel
7 tests
2) Sodium, potassium, chloride, bicarb(onate), BUN, creatinine, glucose
3) Also frequently has eighth test: calcium
Creatinine:
1) Where does it come from?
2) What excretes it? What are levels directly proportional to?
3) Where is it found? Are levels stable?
1) Byproduct of skeletal muscle activity
2) Excreted primarily by the kidneys
Levels directly proportional to renal excretory function
3) Abundant in the body and stable
Skeletal volume and dietary patterns are relatively stable
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Therefore, it is a useful filtration marker to estimate GFR
Doubling of serum creatinine suggests 50% reduction in GFR
Urea formed in the liver as a metabolic byproduct
Ingested proteins broken down into amino acids
Amino acids catabolized to form ammonia
Ammonia converted into urea
BUN is excreted by the kidneys
Levels reflect metabolic health of the liver and excretory health of the kidneys
Glucose
Regulated via insulin and glucagon
Must be evaluated in relation to mealtime
Example: 135 is high in fasted state but not abnormal 1 hour post-prandial (PP)
Follow up testing with glycosylated hemoglobin (HbA1c)
Glucose
Increased
DM, Cushing’s, pancreatitis, steroids, physiologic stress (CVA, MI, shock)
Decreased
Starvation, hypothyroidism, excess insulin administration
Bicarbonate
AKA CO2 or total CO2 (different from pCO2)
Most of the body’s CO2 is in the form of bicarbonate (HCO3-)
CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-
CO2 itself is a metabolic byproduct
Bicarbonate
Used in the evaluation of pH status
Technically bicarb can act as an acid or a base but in acid-base/blood gas analysis it acts as a base
Normal range of HCO3: 22-26 mEq/L
1) List the extracellular electrolytes
2) List the intracellular ones
1) Sodium
Calcium
Chloride
Bicarbonate
2) Potassium
Magnesium
Phosphate
Electrolytes:
1) What are they?
2) What are they important from?
3) What regulates their concentration throughout the body?
Minerals with electric charges that dissociate in a solution into + or – ions
Maintenance of physiologic body fx, cellular metabolism, neuromuscular fx, osmotic equilibrium.
3) Homeostatic mechanisms
Electrolytes
Serum electrolytes are maintained within a narrow range by the kidneys
May not correlate with total body levels due to shifting of water or electrolytes in and out of cells
Urine concentration of an electrolyte is helpful when compared to serum levels
Can determine if kidneys are excreting/retaining electrolyte in response to high/low serum levels
Gold-standard – 24-hour urine collection to monitor electrolyte excretion
Can be cumbersome and challenging
Fractional excretion (FE) of an electrolyte is more convenient
Fractional excretion (FEx)
Compares a substance in a spot urine sample to the serum levels and also to creatinine
Low fractional excretion indicates ________
High fractional excretion indicates ________
Can be used to determine if kidneys are responding appropriately to a specific electrolyte disorder
True or false: osmolarity and osmolality are used interchangeably in clinical med
True
Osmolality of all solutes (electrolytes and others) in plasma is 280-295 mmol/kg
Water moves from region of low osmolality to high osmolal
What are the major fluid compartments?
Intracellular (ICF): inside cell
Extracellular (ECF):
Interstitial (surrounding cells)
Plasma (intravascular)
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Water is balanced between the intracellular compartment and extracellular compartment (including serum)
Water will move (towards compartment with higher solute concentration) to balance the concentrations until there is equilibrium
Sodium
The main extracellular cation
Main determinant of extracellular osmolality (affects fluid shifts)
Balanced between dietary intake and renal excretion
Hyponatremia is the most common electrolyte abnormality
Describe what ADH does
Actions: Kidney reabsorbs water (concentrates urine)
Consequently dilutes serum Na+ (lowering concentration)
-Main stimulators are increased plasma osmolality and decreased blood volume
Describe what aldosterone does and what causes it to be released
Actions: Increases tubular reabsorption of Na+ (excretes K+ and H+); water is also reabsorbed (follows Na+)
Stimulators of Release:
Most powerful stimulator is angiotensin II (e.g., renin-angiotensin-aldosterone [RAAS] system)
Natriuretic peptide hormones
Actions: Increase Na+ excretion (sodium lost in urine); water is also excreted (follows Na+)
Stimulators of Release: Myocardial stretch
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Closely related to body’s fluid status
Disorders of sodium are (generally) disorders of water (see following slides)
Hyponatremia (low serum Na+):
1) What does it represent?
2) What is it usually due to? Give an example
1) Represents an excess of water relative to sodium in the serum
Usually due to an excess of total body water diluting serum Na+, rather than a deficiency in total body Na+
Example: increased PO or IV water
Hyponatremia (low serum Na+):
1)
Serum osmolality: Usually low (hypotonic), but sometimes normal (pseudohyponatremia) or increased (hypertonic)
Water moves to compartment with greater solute concentration (cells)
Cells will swell (can cause cerebral edema, seizures, brain herniation)
Hypernatremia (high serum Na+)
Usually due to water loss > intake
(i.e. rarely due to too much Na+ except when too much hypertonic fluid is given)
Too little water relative to Na+ in the serum (concentrating serum Na+)
Hypernatremia (high serum Na+)
Water moves to compartment with greater solute concentration (the blood)
Cells shrink
Serum osmolality: always high (unlike hyponatremia, which can be variable)
Hyponatremia:
1) Describe the acute Sx
2) Describe the chronic Sx
3) When may the chronic Sx be different?
1) headache, difficulty concentrating, disorientation, nausea (early) progressing to vomiting, LOC, seizure, brainstem herniation, death
2) usually asymptomatic (brain cells adapt to hypotonicity); may be found on routine testing
-May have subtle sxs like mild concentration deficit, nausea, gait issues
Quickly reversing chronic hyponatremia can lead to neurologic complications (osmotic demyelination syndrome)
Hypernatremia
1) What are the clinical features?
2) When are there going to be acute features? List them
1) Signs of volume depletion (e.g., dry mouth and mucous membranes, lack of tears, tachycardia, hypotension, oliguria/anuria)
2) Acute and severe symptoms with Na+ >160:
lethargy, irritability, weakness, hyperreflexia progressing to hyperthermia, delirium, seizures, coma (irreversible neurologic damage if untreated)
Overhydration status (oral or IV)
More water is ingested than the kidney can excrete (often due to ADH)
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: (Measure serum osmolality)
Pseudohyponatremia (normal serum osmolality) – rarer as lab technology improves
Severe hypertriglyceridemia or hypergammaglobulinemia throws off sodium reading
Hypertonic (hyperosmolar) hyponatremia
Hyperglycemia and (less common) mannitol infusion
Increase osmolality of ECF which pulls fluid from cells
Hypertonicity will still stimulate thirst and ADH secretion, contributing to water retention
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Calculate “corrected” sodium if hyperglycemia:
Increase sodium by 1.6 for every 100mg/dL rise in plasma glucose above normal (100 mg/dL)
(See example on later slide)
What is the most common hyponatremia? What are its 2 categories?
Hypotonic (hypo-osmolar) hyponatremia most common (water intake exceeds kidney’s excretional capacity)
Further divided into ADH independent and ADH dependent (measure urine osmolality)
slide 26 chart
slide 26 chart
ADH independent causes – ADH is appropriately suppressed; kidney’s ability to excrete water is intact (urine osm <100, dilute urine)*
i.e. The problem is not due to ADH causing water retention. Pt cannot excrete enough of the excess water for another reason.
List Hyponatremia: Etiologies (con.)Hypotonic – ADH Independent
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slide 28
) ADH dependent causes: most common category of hypotonic hyponatremias (urine osm >100, concentrated urine)
involve failure to suppress ADH; water is retained
This is the appropriate response to hypovolemia or reduced effective arterial volume (e.g., hypervolemic states like cirrhosis or heart failure)
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Can be inappropriate in the absence of hypovolemia or edematous states
Aka syndrome of inappropriate ADH secretion (SIADH)
Categorized by pt volume status (hypo-, eu-, or hypervolemic)
(also evaluate urine sodium)
Hyponatremia: Etiologies (con.)Hypotonic – ADH Dependent - Hypovolemic
1) When does it occur?
Occurs with renal or extrarenal volume loss (various causes) and subsequent hypotonic fluid replacement
Fluid loss happens (water and sodium is lost)
Then pituitary secretes ADH to limit water excretion to maintain blood pressure (sacrifices serum osmolality to preserve intravascular volume)
Water retained, remaining sodium diluted
Then hypotonic fluids are given, further diluting the sodium
Hyponatremia: Etiologies (con.)Hypotonic – ADH Dependent - Hypervolemic
Usually occurs in the setting of edematous states (cirrhosis, heart failure, rarely nephrotic syndrome)
Cirrhosis – systemic vasodilation (primary cause; multifactorial)
Heart failure – reduced cardiac output
Nephrotic syndrome – urinary loss of albumin leads to third spacing of fluid outside of vessels
Decreased effective circulating volume (e.g., to kidneys) triggers ADH secretion and RAAS activation, even though there is already excess extracellular fluid (edema)
Because of RAAS activation and increased aldosterone, urine sodium is low
Hyponatremia: Etiologies (con.)Hypotonic – ADH Dependent - Euvolemic SIADH – syndrome of inappropriate ADH secretion
ADH secreted in the absence of appropriate physiologic stimuli (e.g., decreased effective circulating volume, hyperosmolality)
Other issue (e.g., CNS or lung disorders [cancer/infections], medications) leads to ADH secretion
Hyponatremia: Etiologies (con.)Hypotonic – ADH Dependent - Euvolemic SIADH – syndrome of inappropriate ADH secretion
Diagnosis of exclusion after ruling out other causes of hyponatremia
Hyponatremia with decreased plasma osmolality, high urine sodium; no heart/kidney/liver disease, normal thyroid and adrenal function
Reset osmostat:
Rare condition in which pts regulate ADH release around a lower (hypotonic) set point (mild form occurs in pregnancy)
Adrenal insufficiency and severe hypothyroidism:
Cortisol normally inhibits ADH release (negative feedback)
Deficiency of cortisol means more ADH is released (disruption of ADH “off-switch”) can lead to hyponatremia
Adrenal insufficiency and severe hypothyroidism:
Myxedema coma (in hypothyroidism) may cause hyponatremia
May be due to reduced cardiac output and concurrent adrenal insufficiency increasing ADH activity
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Lab considerations
Serum and urine electrolytes (specifically Na+)
Serum and urine osmolality
Urine osmolality is used as a surrogate for ADH activity
(ADH is typically not directly measured in hyponatremia)
Others as indicated (renal function, thyroid function, etc.)
Hypernatremia: oliguria
(urine flow <0.5 mL/minute, low)*
Reduced water intake – patients with inability to communicate or access water for themselves
Nonrenal water loss – sweat, vomiting/diarrhea, respiratory losses (ventilator)
Water shifted into cells due to gain of intracellular osmole – rare, seizures or rhabdomyolysis
Hypernatremia: nonoliguria
Assess urine osmolality
Low (<250 mOsm/kg) [dilute urine]
Diabetes insipidus central (not producing enough ADH) or nephrogenic (not responding to ADH) or release of a vasopressinase
High (>300 mOsm/kg) [concentrated urine]
Hypernatremia with high urine volume and osmolality have osmotic diuresis
likely too much glucose or urea spilling into urine, pulling water with it
slide 41
Urine osmolality will generally be high for the causes listed here
“Third spacing”
1) What is it? What can cause it?
2) What are some S/Sx?
3)
Outdated term
Can be caused by hyponatremia (solute concentration in intravascular space < interstitial space)
Fluid moves out of intravascular spaces to interstitial fluid
Fluid is unavailable for circulatory system
S/sx
Weight gain
Edema
Hypotension
Tachycardia
Decreased Urine output (Uo)
Example: ascites
Factors affecting serum K+ concentration include:
Aldosterone: tends to increase renal losses of K+ (while retaining Na+ and water in blood)
Sodium resorption: as sodium is resorbed, K+ is lost
Acid–base balance:
Alkalotic states/ Metabolic acidosis
Alkalotic states (less H+ in serum) tend to lower serum K+ levels by causing a shift of K+ into the cell (as H+ is shifted out of cell); a similar shift also occurs in renal tubules
Metabolic acidosis (except for organic acidoses) tends to raise serum K+ levels (reverse the H+/K+ shift)
Hypokalemia: Etiologies
Insufficient intake (diet)
Usually not the issue as kidneys can lower excretion to very low levels
Certain diet patterns that are extremely low in K+ (e.g., anorexia nervosa, alcoholism) can deplete stores
Hypokalemia: Etiologies
Potassium shifted into cells
Insulin, beta-adrenergic agonists (e.g., albuterol), alkalosis
GI losses/wasting
Diarrhea, vomiting
Hypokalemia: What are 4 etiologies of renal losses/wasting?
1) Loop diuretics: Can cause substantial potassium and magnesium excretion
-Most common cause of potassium wasting
2) Increased aldosterone
3) Hypomagnesemia
(Magnesium is important in regulating potassium excretion)
4) Others (renal tubulopathies/tubular acidosis, etc.)
Assessing urine potassium can help distinguish renal from non-renal causes of hypokalemia:
1) What is ideal?
2) What is convenient?
Ideal: 24-hour urine collection
Convenient: urine potassium to creatinine ratio (Uk/UCr)
Convenient: urine potassium to creatinine ratio (Uk/UCr)
Comparing the potassium in spot urine sample to the creatinine
Low (kidneys are appropriately preserving K+ in blood) likely nonrenal cause
Evaluate for GI losses (e.g., diarrhea), intracellular K+ shifts, inadequate dietary intake
High (more K+ in urine) likely renal cause
Renal K+ wasting (may be related to acid-base disorder, diuretics, hyperaldosteronism, low magnesium, etc.)
Hyperkalemia (Serum K+ >5.0 mEq/L): Clinical Features
Impairs neuromuscular transmission
Serious manifestations (usually when K+ ≥7.0 mEq/L if chronic or lower if acute)
Ascending muscle weakness or paralysis
Cardiac conduction abnormalities and cardiac arrhythmias (bradycardias, blocks, VT, VF, asystole, etc.) eventual cardiac arrest
Hyperkalemia (Serum K+ >5.0 mEq/L): Clinical Features
1) What are some other potential Sx?
2) What may it directly cause?
Other potential symptoms include: GI (nausea, vomiting, diarrhea), areflexia, paresthesias
May cause metabolic acidosis (interferes with renal NH4+ excretion)
Hyperkalemia: Etiologies
Increased K+ intake (not a common cause alone unless acute)
Increased net K+ release from cells (can cause transient hyperkalemia)
Reduced urinary K+ excretion (can cause persistent hyperkalemia)
Medications (multiple mechanisms)
Pseudohyperkalemia
Issues during blood collection, storage, handling (fist clenching, tourniquet, shaking the tube)
Should be suspected when there is no apparent cause in an asymptomatic patient (repeat lab test)
Tissue breakdown
Tissue damage releases intracellular K+
Trauma/crush injuries, tumor lysis syndrome, severe hemolysis, rhabdomyolysis, hypothermia
Hyperglycemia
Uncontrolled diabetes can cause hyperkalemia
Combination of insulin deficiency and hyperglycemic hyperosmolarity (pulling water and K+ into vessels)
Metabolic acidosis (other than organic acidosis [lactic/keto-acidosis])
H+ moves from blood into cells, whereas K+ moves opposite direction (from cells into blood) to maintain electroneutrality
Beta blockers, digitalis, exercise, RBC transfusion, hyperkalemic periodic paralysis can all cause what?
Increased net K+ release from cells (causing hyperkalemia)
Impaired renal elimination of K+
1) CKD: Usually able to maintain normal K+ until GFR <20-30 (unless other contributing factors)
2) Reduced aldosterone action (deficiency or lack of response)
Aldosterone increases Na+ and water reabsorption, K+ and H+ secretion
Hypoaldosteronism (e.g., Addison disease), meds (e.g., potassium-sparing diuretics), etc.
Impaired renal elimination of K+
1) AKI
Especially in oliguric AKI
2) Low effective circulating volume
E.g., hypovolemia, heart failure, cirrhosis
Reduced Na+ and water delivery to the distal nephron tubule
For K+ to be effectively secreted, there needs to be sufficient Na+ and water in the tubule that can be reabsorbed (exchanged for K+)
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Medications
It is vital to carefully review the pt’s med list
Many potential drug causes of hyperkalemia
Some of the more common ones:
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Consider repeat testing to confirm hyperkalemia (do not delay emergent treatment though)
Especially in patients without kidney disease or medications that cause hyperkalemia
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Make sure to assess renal function (e.g, Creatinine, BUN), acid-base status (e.g, ABG), glucose (e.g., hyperglycemia)
Labs for work-up include BMP (electrolytes, renal function), Mg2+, Ca2+, CBC (e.g., hemolysis), +/- serum osmolality and urine studies (pH, osmolality, creatinine, electrolytes). Others as directed at suspected etiology.
Chloride:
1) What is it?
1) Major extracellular anion
Neuron action potentials and extracellular fluid tonicity
Not useful by itself, interpreted with other electrolytes for acid-base and hydration status
Hypo/hyperchloremia doesn’t usually occur in isolation
Involves shifts in sodium and/or bicarbonate
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Serum calcium (total) is often included on BMP (may need to order separately)
99% of the body’s calcium is in bone
Serum calcium is split between free (ionized) calcium and albumin-bound
Total serum calcium = ionized + albumin-bound
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Total serum calcium: 8.5-10.5 mg/dL (normal)
Ionized calcium
Physiologically active portion of calcium
Necessary for muscle contraction and nerve function
Low ionized Ca2+ = true hypocalcemia implies insufficient action of PTH or active vitamin D
Ionized vs. Total Calcium & Effect of Albumin
Usually measuring total serum calcium is sufficient because changes in total mirror those in ionized fraction
Exceptions (total calcium is low but ionized may be normal) include: hypoalbuminemia, certain acid-base disorders
-When serum albumin is <4 g/dL, serum Ca2+ is reduced by ~0.8 mg/dL* for every 1 g/dL of albumin below normal (4)
If albumin is low, total calcium is expected to be low measure both when evaluating calcium
(Albumin is part of the CMP)
Calcium & Phosphorus
Inversely related in the body
as one rises, the other falls (generally)
PTH causes kidneys to reabsorb calcium but excrete phosphate in urine (raising serum calcium and lowering serum phosphate)
When serum phosphate is high (hyperphosphatemia):
calcium-phosphate complexes precipitate in tissues, lowering serum calcium (hypocalcemia)
also induces PTH secretion to raise calcium and lower phosphate towards normal
Hypocalcemia: Clinical Manifestations
Signs/sxs: depend on severity and chronicity
May be asymptomatic (if not severe)
Hallmark of acute/severe hypocalcemia = tetany (due to neuromuscular irritability)
Symptoms range from mild paresthesias to carpopedal spasm to seizures
Hypocalcemia: Clinical Manifestations
Classic physical findings include:
Chvostek sign, Trousseau sign
ECG: QT prolongation predisposes to ventricular arrhythmias, though serious dysrhythmias are rare
Hypoalbuminemia is most common cause of decreased total serum Ca2+ (but ionized Ca2+ may be normal)
Causes of low albumin include malnutrition, alcoholism, large volume IV infusion
Advanced CKD is most common cause of true hypocalcemia (due to decreased production of calcitriol and hyperphosphatemia)
Hypomagnesemia: reduces PTH release and tissue responsiveness to PTH
Vitamin D deficiency: low serum calcium and phosphate, +/- high PTH
1) What does primary hypoparathyroidism cause?
2) List some other causes of hypocalcemia
1) low serum calcium, high phosphate, low PTH
2) alkalosis (increased pH promotes protein binding, lowering free calcium levels, and vice versa), malabsorption, pancreatitis, diuretics…
Hypercalcemia: Clinical Manifestations
May affect GI, kidney, and neurologic function
ECG: shortened QT interval (if acute), clinically relevant arrhythmias are rare
Hypercalcemia:
1) Common Sx?
2) Complications? (3)
1) Constipation, anorexia, anxiety, cognitive changes (lethargy and stupor if severe)
2)
a) Pancreatitis (calcium deposition in pancreatic ducts)
b) Impaired renal concentrating ability: Polyuria and dehydration
c) Nephrolithiasis (due to hypercalciuria): renal colic, hematuria
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Most common causes (90%):
Asymptomatic, mild hypercalcemia: usually primary hyperparathyroidism
PTH increases GI absorption of calcium, increases urinary reabsorption, increases bone resorption
Symptomatic, severe hypercalcemia: usually malignancy-associated hypercalcemia
Myeloma, breast, lung, renal cell metastases destroy bone and release calcium into blood
Various cancers produce PTH-like substance
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Elevated serum total and ionized calcium
May have hypophosphatemia
Serum PTH levels: used to determine if hypercalcemia is PTH-mediated or not
High: primary hyperparathyroidism is the most likely cause
Low: eval for non-PTH-mediated cause (malignancy, Vit. D intoxication, etc.)
Most magnesium is stored in bones and muscles
Physiologic effects on nervous system are similar to Ca2+
Both hypo- and hypermagnesemia can decrease PTH secretion/action and provoke hypocalcemia
Hypermagnesemia
Advanced CKD (impaired excretion)
Chronic intake of Mg-containing drugs (Antacids, laxatives)
Pregnant pts receiving IV Mg for preeclampsia/ eclampsia
2) Decreased DTRs (earliest finding) weakness, somnolence, confusion, bradycardia, hypotension respiratory muscle paralysis, cardiac arrest
Hypomagnesemia
common etiologies?
GI losses (diarrhea, malabsorption, small bowel bypass surgery, pancreatitis, PPIs)
Urinary losses (loop/thiazide diuretics, alcohol abuse, hypercalcemia, uncontrolled DM)
Hypomagnesemia Clinical Manifestations Include what?
Neuromuscular and CNS hyperirritability (may be from low K+/Ca2+) tremors, cramps, Trousseau/Chvostek signs, confusion, disorientation, convulsions, coma; weakness; hypertension, tachycardia, arrhythmias (e.g., torsades de pointes)
Can cause hypokalemia and hypocalcemia that are refractory to treatment until Mg is fixed
Hypophosphatemia:
Etiologies include: Diminished absorption (e.g., antacids), refeeding syndrome, vitamin D deficiency, hyperparathyroidism
Clinical manifestations related to ATP deficiency (phosphorus is a key ingredient of ATP)
Sx - Muscle weakness, hemolysis. Severe rhabdomyolysis, paresthesia, encephalopathy
Hyperphosphatemia:
Etiologies include: advanced CKD (most common); phosphate-containing laxatives; rapid cell breakdown releasing intracellular phosphate (tumor lysis syndrome, rhabdomyolysis, hemolysis)
Can cause concurrent hypocalcemia
Sx - Usually asymptomatic (may have sxs from hypocalcemia and underlying disorder)
