4 factors which must be controlled in the human body to maintain homeostasis
- Water balance b/w fluid compartments
- Electrolyte balance
- pH: 7.40
- Temperature: 37°C
All water w/in cell membranes; the medium through which CHEMICAL RXNS OF CELLULAR METABOLISM OCCUR
Intracellular fluid
Major ions/constituents in intracellular fluid
- Cations: K+ and Mg2+
- Anions: protein, organic phosphates, sulfates
- Low concentrations of: Na+, Cl-, HCO3-
All water outside of cell membranes; the medium through which all METABOLIC CHANGES occur
Extracellular fluid
Major ions/constituents in extracellular fluid
Interstitial fluid and plasma
The directly measureable plasma is known as what?
Intravascular fluid (plasma)
Major ions/constituents in intravascular fluid
- Large amount of protein
- High concentrations: Na+, Cl-
- Moderate concentrations: HCO3-
- Low concentrations: Ca2+, Mg2+, phosphate, sulfate, K+, organic acids
Fluid that directly bathes the cells of body includes pericardial, pleural, peritoneal, and synovial body fluids; cannot be sampled for direct measurement
Interstitial fluid
Major ions/constituents in interstitial fluid
- High: Na+, Cl-
- Medium: HCO3-
- Low: NO proteins
The force that tends to move water from dilute solutions to concentrated solutions
Osmotic pressure
How do osmotic pressure differences maintain the composition of extracellular and intracellular fluids?
Predominance of K+ in the intracellular fluid and Na+ in the extracellular fluid PLUS plasma proteins that are the major contributors to the osmotic pressure b/w these compartments
What maintains electroneutrality b/w compartments?
Gibbs-Donnan Equilibrium
How does the Gibbs-Donnan equilibrium maintain the composition of extracellular and intracellular fluids
It maintains the electroneutrality b/w compartments by keeping the anion total equaling the total cations (the use of non-diffusable anions is important)
3 chemical constituents that contribute to osmotic pressure differences b/w EXTRACELLULAR and INTRACELLULAR fluid compartments
- K+
- Na+
- Plasma proteins
3 means by which water balance is maintained b/w INTERSTITIAL and INTRACELLULAR fluid compartments
- Membrane characteristics
- Colloid osmotic pressure (COP)
- NaK- ATPase pump
How do passive transport differences maintain an equilibrium b/w intravascular and interstitial fluids, including importance of maintaining normal plasma protein concentrations in homeostasis?
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How do colloid osmotic pressure differences maintain an equilibrium between intravascular and interstitial fluids, including importance of maintaining normal plasma protein concentrations in homeostasis?
Protein in the plasma causes water to move into the plasma from the interstitial fluid b/c there is no protein in the ISF. This movement is from colloid osmotic pressure
How do hydrostatic pressure differences maintain an equilibrium between intravascular and interstitial fluids, including importance of maintaining normal plasma protein concentrations in homeostasis
Hydrostatic pressure from the heart causes fluid to move from the plasma into the interstitial fluid
How do colloid osmotic pressure differences maintain an equilibrium between interstitial and intracellular fluids
Because there is protein in the cells and not in the interstitial fluid, water flows from the interstitial fluid to the cells due to osmotic pressure
How do membrane characteristics (lipid solubility, size of solute, water permeability, and charge) maintain an equilibrium between interstitial and intracellular fluids
Permeability is directly related to lipid solubility and size and inversely related to the water solubility of the solute
How does the NA-K-ATPase pump maintain an equilibrium between interstitial and intracellular fluids
The pump actively pumps sodium out of cells and pumps in K+ maintaining equilibrium
Why is the NaK-ATPase pump necessary for water balance?
Keeps the water balanced b/w the interstitial and intercellular fluids
NaK-ATPase pump movement of substances IN and OUT of the cell
- Water?
- Na+?
- K+?
- Water: out (follows Na+)
- Na+: out
- K+: in
How does the hypothalamus regulate water balance?
Neurons shrink and hypothalamus signals need for water
Four stimuli for both the water-intake and water-output areas of the hypothalamus
- ↑ extracellular water osmolarity
- Angiotensin II
- ↓ in intravascular volume (leading to ↓ distension receptor activity)
The effect of stimulation of both the water intake and water output areas of the hypothalamus
- Water input: ↑ thirst
- Water output: ↑ ADH secretion from posterior pituitary
The net effect of hypothalamic stimulation on water balance
- Water input: ↑ free water intake
- Water output: ↓ free water output by kidney
Primary stimulus for antidiuretic hormone (ADH) release
Increase in ECW osmolality
Natriuretic peptides
- Two conditions that result in the release and increase in the blood
Secreted in response to intravascular volume expansion and defend against salt-induced CHF
Natriuretic peptides
- Source and three physiological effects of atrial natriuetic peptide (ANP)
- Source: cardiac atria
- Effects: reduce the increase in venous pressure, increases vascular permeability and promotes natriuresis and diuresis
Natriuretic peptides
- Source and three physiological effects of brain natriuetic peptide (BNP)
- Source: produced in cardiac ventricles
- Effects: cardiovascular, natriuretic, and diuretic effects similar to ANPq
Natriuretic Peptides
- Three sources and one physiological effect of C-type natriuretic peptide (CNP)
- Source: brain, vascular endothelial cells, renal tubules
- Effect: venous dilator
What is the effect ADH has on the renal collecting ducts?
Stimulation of water output area of the hypothalamus causes pores of the collecting ducts to become more permeable to water (↑ water reabsorption)
Causes of extracellular fluid loss
- Trauma (and other causes of acute blood loss)
- Burns
- Pancreatitis, peritonitis
- Vomiting, diarrhea, diuretics
- Renal or adrenal disease taht causes salt wasting
Causes for hypernatremic dehydration
- Water and food deprivation
- Diabetes insipidus
- Excessive sweating
- Osmotic diuresis association w/ glucosuria
- Diuretic therapy
Causes of extracellular fluid gain
- Heart failure
- Hepatic cirrhosis
- Nephrotic syndrome
- Intravenous fluid overload
The most common cause of water intoxication
Extracellular fluid gain caused by syndrome of inappropriate ADH secretion (SIADH)
Sodium reference range
136-145 mEq/L
Four functions of sodium
- Maintain normal H2O distribution
- Maintain normal osmotic pressure
- Neuromuscular processes
- Acid-base balance
Contrast diabetes and the syndrome of inappropriate ADH (SIADH) secretion according to ADH and sodium levels
Diabetes inspidus - High urinary output - Low levels ADH - Hypernatremia - Dehydrated - Loss of too much fluid SIADH - Low urinary output - High leevls of ADH - Hyponatremia - Overhydrated - Retains too much fluid
Sodium is a major ____ cation
Extracellular
Three renal processes by which normal levels of sodium are maintained in the body
- Kidneys-filtered in the glomeruli; reabsorption in the PCT, loops of Henle, and DCT
- Aldosterone controls Na+ in DCT
- BNP gets rid of Na+
Depletional hyponatremia causes ____ hyponatremia
Absolute
Two general causes of depletional hyponatremia
- Renal loss
- Non-renal loss
Two general causes of renal losses in depletional hyponatremia
- Diuretic loss
- Hypoaldosteronism
Two general causes of non-renal losses in depletional hyponatremia
- GI loss
- Skin loss
3 general causes of hyponatremia
- Depletional
- Dilutional
- Pseudohyponatremia
Dilutional hyponatremia is a ____ hyponatremia
Relative
Two general causes of dilutional hyponatremia
- SIADH
- Hyperglycemia
Why does SIADH and hyperglycemia lead to increased water volume in dilutional hyponatremia?
- ADH is secreted all the time, which causes use to retain H2O diluting Na+
- Increased glucose in urine causes it to be diluted w/ H2O
Two general causes of pseudohyponatremia
- Hyperlipidemia
- Hyperproteinemia
Why does hyperlipidemia and hyperproteinemia cause low sodium results in pseudohyponatremia?
Displaces some H2O, picks up more lipids or protein than plasma H2O
Three general causes of hypernatremia due to water loss
- GI losses
- Excessive sweating
- Diabetes insipidus
Three general causes of hypernatremia due to sodium gain
- Ingestion or infusion of Na+
- Primary hyperaldosteronism (tumor)
- Secondary hyperaldosteronism
Two general causes of hypernatremia
- Water loss
- Sodium gain
Reference range of potassium
3.5-5.0 mEq/L
Two functions of potassium
- Regulation of many cellular processes
- Neuromuscular excitation (heart)
Three general causes of hypokalemia
- Increased cellular uptake
- Increased renal loss
- Excessive GI loss
Why does excess insulin cause hypokalemia?
Too much glucose and potassium
Why does alkalosis compensation cause hypokalemia?
Need more acid in bloodstream so RBCs push H+ ions into blood and take up more K+
Four general causes of hypokalemia due to renal loss
- Hyperaldosteronism
- Diuretic theory
- Licorice ingestion
- Renal tubular acdiosis
Three general causes of hypokalemia due to excessive gastrointestinal loss
- Vomiting
- Diarrhea
- Laxative abuse
Five general causes of hyperkalemia
- Increased intake
- Increased cell lysis
- Altered cellular uptake
- Impaired renal excretion
- Pseudohyperkalemia
Three causes of hyperkalemia due to increased intake
- Txn of aged blood
- Supplements
- Bananas
Three general causes of hyperkalemia due to increased in vivo cell lysis
- Cellular trauma
- Cellular injury
- In vivo hemolysis
Two general causes of hyperkalemia due to altered cellular uptake
- Compensation for acidosis (H+ taken into cell, K+ pushed out = electroneutrality)
- Insulin deficiency
Two general causes of hyperkalemia due to impaired renal excretion
- Renal insufficiency or failure
- Hypoaldosteronism
Reference range of chloride
99-109 mEq/L
Chloride is a major ____ anion
Extracellular
Three functions of chloride
- Maintains H2O balance
- Maintains osmotic pressure
- Acid-base balance w/ “chloride shift”
Three general causes of hypochloremia and associated conditions
- GI losses → prolonged vomiting, nasogastric suctioning
- Burns → tissue trauma
- Renal losses → diuretic therapy, compensation for metabolic acidosis
Two general causes of hyperchloremia and associated conditions
- Dehydration
- Renal tubular acidosis → Na+ gain
- Compensation for metabolic alkalosis
REMEMBER: Cl- levels altered in same direction as Na+ = ____ ____
Water imbalance
REMEMBER: Cl- levels not proportional to Na+ = ____ ____ ____
Acid-base imbalance
Clinical usefulness of sweat chloride measurements
Sweat induced by pilocarpine iontophoresis; cystic fibrosis detected if >60 mEq/L and normal if <40 mEq/L
Reference range of bicarbonate
22-28 mEq/L
Function of bicarbonate
- Levels regulated by the kidney
- Decrease in metabolic acidosis
- Increase in metabolic alkalosis
Bicarbonate is the 2nd most important ____ anion
Extracellular
Not all ions measured when electrolytes are performed so a gap exists because of contribution of unmeasured anions: protein, sulfate, phosphate, and organic acids
Anion gap
Why is the anion gap an expected occurrence?
- The body exists in a state of electroneutrality, but not all ions are “measured” when electrolytes are performed
- The “gap” exists b/c of the contribution of unmeasured anions: protein, sulfate, phosphate, and organic acids
Clinical purpose of anion gap calculation
To estimate unmeasured anions
Laboratory purpose of anion gap calculation
Instrument error determines acceptability of results
Expected range of anion gap using [(Na+K)-(Cl+HCO3)]
12-20 mEq/L
Expected range of anion gap using [(Na)-(Cl+HCO3)]
8-16 mEq/L
Three general causes of an increased anion gap and two conditions associated w/ each
- Increased unmeasured anions → Lactic acidosis, ketoacidosis, toxic ingestion
- Decreased unmeasured cations → decreased Ca2+ and Mg2+
- Lab error → overestimation of Na+ or underestimation of Cl- or HCO3-
Three general causes of a decreased anion gap and one condition associated w/ each
- Decreased unmeasured anions → hypoalbuminemia
- Increased unmeasured cations → K+, Ca2+, Mg2+, paraproteins
- Lab error → underestimation of Na+, overestimation of Cl- or HCO3-
Reference range of calcium
8.5-10.5 mg/dL
Four functions of calcium
- Decreases in neuromuscular excitability
- Blood coagulation
- Activator in enzymatic reactions
- Transfer inorganic ions across cell membranes
Three forms of Ca2+ in the blood
- Bound
- Filterable: ionized
- Filterable: complexed
Physiologically active form of Ca2+ in the blood
Filterable ionized
Five factors that control serum Ca2+ levels
- Absorbed in GI tract; alkali and presence of fat interferes w/ absorption
- Parathyroid hormone (PTH) (↑ Ca2+)
- Calcitonin (↓ Ca2+)
- Vitamin D (↑ Ca2+)
- Protein (ALB) levels
Seven causes of hypocalcemia
- Decreased serum protein (most common)
- Hypoparathyroidism
- Steatorrhea
- Nephrosis
- Pancreatitis
- Vitamin D deficiency
- Heparin during surgery
Three causes of hypercalcemia
- Metastatic bone disease (most common)
- Multiple myeloma
- Hyperparathyroidism
List the most common cause of hypercalcemia
Metastatic bone disease (secondary to cancer of breast, lung, and kidney)
Two reasons why profoundly decreased ionized Ca2+ levels may be fatal
- Causes tetany, seizures, hypotension, ↓ cardiac function
- Enhances hyperkalemia = fibrillation and cardiac standstill
Reference range of Mg2+
1.9-2.5 mg/dL
Three functions of magnesium
- Activator in enzymatic reactions (transfer/storage)
- Crucial in cellular physiology
- CHO, lipid, protein, and nucleic acid metabolism
Two general causes of hypomagnesemia and two specific conditions associated w/ each
- Impaired intake → malabsorption, malnutrition, diarrhea, alcoholism
- Excessive renal loss → diuretics, hyperaldosteronism, and primary hyperparathyroidism
Three general causes of hypermagnesemia
- Renal failure
- Magnesium intoxication
- Treatment of toxemia of pregnancy (MgSO4 excess)
Reference range of phosphorus
2.5-4.5 mg/dL
Five functions of phosphorus
- Major intracellular anion
- Metabolism closely related to Ca2+
- Intermediary metabolism
- Component of phospholipids, nucleic acids, and ATP
- Bone mineralization
- Minor plasma buffer
Five general causes of hypophosphatemia
- RIckets
- Hyperparathyroidism
- Fanconi’s syndrome
- Hemolytic anemia
- Diabetes mellitus
Four general causes of hyperphosphatemia
- Glomerular renal failure
- Hypervitaminosis D
- Hypoparathyroidism
- Bone repair
of moles of solute particles dissolved/kg H2O (w/w soln)
Osmolality
Reporting units for osmolality
mOsmol/kg H2O (w/w)
Reporting units for osmolarity
mOsmol/L H2O (w/v)
Three substances that have the greatest effect on serum osmolality
Na+, glucose, urea
Clinical use of serum osmolality measruement
Determine the presence of “unmeasured substances” in blood
Reference range for serum osmolality
280-300 mOsm/kg
Seven conditions in which serum osmolality may be increased
- Severe dehydration
- Renal failure
- Alcohols
- Ethylene glycol
- Ketone bodies
- Lactic acid
- Mannitol adminstration
Clinical use of urine osmolality measurement
Assess renal concentrating and diluting ability
Reference range of urine osmolality
300-1000 mOsm/kg
Three specific conditions in which the urine osmolality is decreased
- Diabetes insipidus
- Polydipsia
- Renal failure
One specific condition in which the urine osmolality is increased
Syndrome of Inappropriate ADH Secretion (SIADH)
Calculation for serum osmolality
(1.86 x Na+) + (BUN/2.8) + (Glucose/18)
Calculation for osmolality gap
Measured serum osmolality minus calculated serum osmolality
Three methods by which Na+ and K+ may be quantitated
- Atomic absorption spectroscopy (reference method)
- Flame photometry (old method)
- Ion-selective electrodes (most common)
Chloride Method Principle
- Chloride is able to displace thiocyanate from mercuric thiocyanate. The reacts w/ ferric iron to form a red complex
Colorimetric (mercuric thiocyanate and ferric nitrate)
Chloride Method Principle
- Titration that is the reference method for chloride
Coulometric/amperometric
Chloride Method Principle
- Most common today; uses a silver/silver chloride reference electrode
Ion-selective electrode
Chloride Method Principle
- Based on determination of chloride-dependent alpha-amylase activity
Enzymatic (chloride method)
Chloride Method Principle
- Pilocarpine iontophoresis
Sweat chloride (iontophoresis)
Chloride Method Principle
- Purpose of reagents in the sweat chloride test
????
What is the historical calcium precipitation method and two specific dyes used in the spectrophotometric method for measuring calcium
- Historical method: was precipitation with oxalate (Clark and Collip method)
- Spectrophotometric: o-cresolphthalein or arsenazo III
Three reagents used in photometric magnesium methods
- CalMAGite
- Formazan
- Methylthymol blue
Reagent used in the most common phosphorus method
Photometric method
- Reaction of phosphate ions with ammonium molybdate, measured by UV absorption or reduction to the colored compound molybdenum blue
Specimen and anticoagulant interferences for sodium method
- Can analyze serum, plasma, whole blood, urine, or other
- No Na+ in anticoagulant
- Separate serum/plasma from cells w/in 3 hours
Specimen and anticoagulant interferences for potassium method
- Can analyze serum, plasma, whole blood, urine, or other
- No K+ salt in anticoagulant
- No hemolysis for K+
- Separate serum/plasma from cells within 3 hours to prevent K+ leakage
Specimen and anticoagulant interferences for chloride method
- Serum or heparinized plasma
- Sweat chloride by pilocarpine iontophoresis
Specimen and anticoagulant interferences for bicarbonate/total carbon dioxide method
- Serum, heparinized plasma, or whole blood (usually blood gas specimen)
- Handled anaerobically b/c loss of CO2
Specimen and anticoagulant interferences for magnesium method
- Serum or heparinized plasma
- NO HEMOLYSIS
Specimen and anticoagulant interferences for calcium method
- Serum or heparinized plasma
- Promptly separate from cells to prevent uptake of Ca2+ by RBCs
- CANNOT use anticoagulants such as EDTA, oxalate, or fluoride that chelates or precipitate calcium
Specimen and anticoagulant interferences for phosphorus method
- Serum or heparinized plasma
- No EDTA or citrate or oxalate anticoagulatns as they interfere w/ formation of phosphomolybdate complex
- NO HEMOLYSIS
- Separate from cells promptly
Electrolytes for which a hemolyzed specimen is NOT acceptable
- K+
- Mg2+
- Phosphorus
Intracellular cations/anions
- Rank in order of importance
- K+
- Magnesium
- Phosphorus
Extracellular cations/anions
- Rank in order of importance
- Na+
- Bicarbonate
- Cl-
When total body water is increased; serum sodium is decreased
ECF gain (overhydration, water intoxication)
Symptoms of extracellular fluid gain
- Weight gain
- Edema
- Dyspnea
- Tachycardia
- Jugular venous distension
- Portal hypertension
- Esophageal varices
