Lecture 2 - Electrolytes

Osmolality (I):

1) What is this measurement based on?

2) What are the Colligative Properties this is related to?

3) How is Osmolarity different?

1) Based on the number of solutes per Kg of solvent → mOsm

2) Colligative Properties:

• Increased Osmotic Pressure and Boiling Point

• Lowered Vapor Pressure

• Decreased Freezing Point

3) osmolarity is measured as solutes/L of water and is less accurate in the presence of:

• Hyperlipidemia, Proteinemia

• Urine specimens

• Ethanol or mannitol

Osmolality (II):

1) What are the major ions and minor ions contributing to Osmolality?

2) What causes increased and Decreased Serum Osmo?

3) What causes increased and decreased Urine Osmo?

1) Contributors:

• Major → Na(50%), Cl, HCO3

• Minor → BUN, glucose, organic substances (ethanol, methanol)

2) Serum Osmo:

• Increased → DM, Renal Diseases, ETOH and MetOH poisoning

• Decreased → MI and shock

3) Urine Osmo:

• Increased → Fluid Restriction, DM

• Decreased → Overhydration, DI, CRF

Osmolality (III):

1) Why is this important in the plasma?

2) What ion concentration is mainly affected?

3) If any changes in plasma Osmolality occurs, what will be activated?

4) What is the Normal levels?

1) Osmolality in plasma is the parameter to which the hypothalamus responds

2) Mainly affects Na+ with related anions

3) Changes in Osmolality stimulates/inhibits thirst receptors and ADH secretions

Osmolality (IV):

1) When measuring serum or urine Osmolality samples, what are some considerations?

2) How can Osmolality be calculated?

3) What is the Osmolality Gap and its significance?

1) Samples should be:

• Free of Particulate Matter

• Centrifuged if samples are turbid or urine

2) Calculated → (1.86) x (Na) + (Glu/18) + (BUN/2.8) + (9)

3) Osmo Gap is the difference between measured and calculated

• Indirectly indicates the presence of osmotically actives substances other than Na, Glucose, or Urea such as ETOH, MetOH, IsoPropanol, Lactate, or B-hydroxybutyrate

What are the Reference Intervals for:

• Urine (24H)

• Urine/Serum Ratio

• Random Urine

• Osmolality Gap

• Urine (24H) → 300 - 900 mOsm/Kg

• Urine/Serum Ratio → 1.0 - 3.0

• Random Urine → 50 - 1200 mOsm/Kg

• Osmolal Gap → 5 - 10 mOsm/Kg

Sodium:

1) Where is this ion mainly found?

2) What is the normal ranges and Critical Values?

1) Major EC Cation found in:

• 30% in bones, 70% in fluids

• Also I’m gastric and intestinal fluids, CSF and sweat

2) RI:

• Normal

  • Serum (136-145 mmol/L)

  • Urine (40-220 mmol/24h)

• Critical (< 115 or > 160 mmol/L)

Hyponatremia (I):

What are the possible causes?

• Sodium Depletion

  • Ex. Renal Loss, GI Loss, Skin Loss, Insufficient Intakes

• Sodium Dilution in Serum

  • Ex. CHF, Cirrhosis, NS (generalized edema)

• Excess Water Intake

• SIADH

• Pseudo-Hyponatremia

• Spurious

Hyponatremia (II):

What are the Characteristics and Clinical Features of:

1) Hypertonic Hyponatremia

2) True Hypotonic

3) Normotonic Hyponatremia

1) Hypertonic Hyponatremia:

• Greater than 295 mOsm/Kg

• Marked Hyperglycemia

• Associated with Mannitol Therapy

2) True Hypotonic Hyponatremia:

• Less than 280 mOsm/Kg

• Hypovolemic → renal sodium loss or extra renal route

• Euvolemic → SIADH, psychogenic polydipsia

• Hypervolemic → CHF, NS, cirrhosis

3) Normotonic Hyponatremia:

• Increased non-sodium cations (Ex. Severe hyperkalemia, hypercalcemis, increased gamma globulins as in MM’

Hypernatremia:

What causes it?

• Increased Sodium:

  • High Diet Intake

  • IV infusion

  • Conn syndrome

• Water Depletion:

  • Excess water loss in individuals unable to respond to thirst

  • GI Loss

  • Excessive sweating

  • Renal Water Loss (diuretics, medullary renal disease)

  • DI (nephrogenic, neurogenic)

Potassium:

1) Where is this mainly found?

2) What is the RI for:

• Serum

• Urine

• Critical Values

1) Major IC Cation:

• mostly in muscle cells

• From dietary intake

• Mostly reabsorbed in PCT and secreted in DCT

• Also found in Gastric fluid, intestinal fluid, and CSF

2) Reference Intervals:

• Serum (3.5 - 5.0 mmol/L)

• Urine (25 - 150 mmol/24h)

• Critical Values (<2.5 or >6.5)

What are the main mechanisms/causes of Hypokalemia?

• Insufficient diet intake

• Renal Loss

  • Hyperaldosteronism (Urine K+ > 30 mmol/L) as in Conn Syndrome

  • Diuretics

  • Hypomagnesemia (via ROMK)

  • RTA I and II

• GI Loss

  • Urine K+ is low (< 30 mmol/L)

  • Vomiting, diarrhea

• Trans cellular shift, especially in metabolic alkalosis

What are the mechanisms/causes of Hyperkalemia?

• High dietary intake

• Increased cellular release

• Therapeutic K+ administration

• Acidosis

• Insulin deficiency

• ARF

• Hypoaldosteronism

• Pseudo-hyperkalemia

Chloride:

1) What is its main function?

2) Where is it found?

3) What is the RI:

• Serum

• Urine

• Critical Values

1) Major EC anion that helps to maintain anion-cation balance (electroneutrality) via Cl shift

2) Found in plasma, gastric fluid, intestinal fluid, and CSF, also in sweat (diagnostic for CF)

3) RI:

• Serum ( 99 - 109 mEq/L)

• Urine (110-250 mEq/L)

• Critical Values (<70 or >120)

What are main mechanisms/causes of Hypochloremia?

• Prolonged vomiting

• Diabetic ketoacidosis (DKA)

• Aldosterone deficiency

• Salt-losing renal diseases such as pylonephritis

• Compensated respiratory acidosis or metabolic alkalosis

What are the main mechanisms/causes of Hyperchloremia?

• dehydration

• RTA

• Metabolic acidosis

• High salt intake

Bicarbonate (HCO3-):

1) What is its function?

2) Where is it found?

3) What is the RI in Serum?

1) Major component of total CO2 in plasma that plays an important role in the bicarbonate-carbonic acid buffering system

2) HCO3- is the transport form of CO2:

• mostly reabsorbed in renal tubules

• Also contained in CSF

3) Serum (22-28 mEq/L)

How are Bicarbonate levels measured analytically?

Analytical method includes:

• CO2 from sample diffuses through a semipermeable membrane into an electrolyte solution

• Change in pH is measured

• Serum or plasma; specimens kept capped

Anion Gap:

1) What is it?

2) What are two ways to calculated it and the RI?

3) What can cause Large AGAP?

1) calculation of the difference between measured anions and cations

2) Calculated by:

• Na - (Cl + HCO) → 7-16

• (Na+K) - (Cl+HCO3) → 10-20

3) can be due to:

• excess unmeasured anions such as PO4 and SO4 (i.e. uremia/RF)

• Also with organic acids, lactic acid, methanol poisoning, salicylate poisoning, and instrument error

Calcium and Phosphorus (Calcium Phosphate Crystals):

1) What are the two forms of Calcium and how do they differ?

2) What is the RI:

• Ca

• Phos in adults and children

1) Forms of Ca:

• Non-Diffusible

  • Bound form (45-50% total Ca bound to Albumin)

  • In hypoalbuminemia, Total Ca is decreased

• Diffusible

  • Free (ionized)

  • Physiologically active form

  • Can cross blood-brain barrier

2) RI:

• Ca (9-11 mg/dL or 2.25-2.75 mmol/L)

• Phosphorus

  • Adults (3.0-4.5 mg/dL or 0.75-1.1 mmol/L)

  • Children (4.5-6.5 mg/dL or 1.1-1.6 mmol/L)

What are the Clinical Features associated with Hypercalcemia and Hypocalcemia?

• Hypercalcemia:

  • May present with lethargy, hyporeflexia, nausea, vomiting

  • Increased risk of pancreatitis and peptic ulcers

  • Hyperparathyroidism

  • Hypervitaminosis D

  • Multiple Myeloma (CRAB Syndrome)

• Hypocalcemia:

  • Neurologic excitability, hyper-reflexia, periorbital tingling (parasthesia) muscle spasm

  • Classic Chvostek and Trousseau signs

  • In severe cases, may lead to tetany and respiratory arrest

  • Hypoparathyroidism

  • Decreased absorption (steatorrhea)

  • Nephrosis (excess protein loss)

What are the Clinical Features associated with Hyperphosphatemia and Hypophosphatemia?

• Hyperphosohatemia:

  • Hypoparathyroidism

  • Hypervitaminosis D

  • Renal Failure

• Hypophosphatemia:

  • Hyperaparathyroidisk

  • Rickets

  • Fanconi Syndrome

  • Absorption problems (Ex. Sprue and Celiac Disease)

What are the Clinical Features of Hyperparathyroidism and Hypoparathyroidism?

• Hyperparathyroidism:

  • Primary → causes irreversible renal damage

  • Secondary → caused by renal disorders, which increases serum Phos and decreases serum Ca

• Hypoparathyroidism:

  • Iatrogenic

  • Mostly caused by thyroidectomy

  • Decreased urinary excretion of P

  • Decreased 1,25 (OH)2 or calcitrol levels

  • Lab Shows:

    • Low → serum/urine Ca, PTH

    • High → serum Phos

    • Normal ALP

    • pH alkalosis leading to Hypocalcemia

What are some important considerations for Sample Collection and Requirements for Ca and Phos?

• Serum or lithium heparin plasma collected without venous stasis

• Avoid citrate, oxalate, or EDTA

• For Calcium:

  • Keep ionized Ca capped

  • Urine specimens should be acidified before analysis

• For Phos:

  • No hemolysis

  • Circadian rhythm with highest levels in late morning and lowest in the evening

  • 24-hour urine required due to significant diurnal variation

What are the two types of Metabolically Produced Acids related to Blood Gases?

• Volatile Acid

  • Includes CO2, which can be removed by the lungs

• Non-Volatile Acids

  • Uric acid, phosphoric acid, sulfuric

  • Cannot be removed by lungs; must be excreted via kidney

  • Present mainly as conjugated salts (H+ neutralized by body buffers)

Body Buffers:

1) What happens when is acid is added to the body?

2) What happens when base is added?

3) What is the Henderson-Hasselbalch Equation?

1) H+ combines with HCO3- to form H2CO3, CO2 is eliminated through lungs and H+ as water

2) OH- combines with H2CO3 to form H20 and HCO3-, which will be taken up by the kidneys

3) pH = pK + log [HCO3-]/[H2CO3]

Blood Gases:

1) What is [H2CO3] measured as?

2) How is it calculated?

3) what is total CO2?

4) Under normal conditions, what are the characteristics of the buffer system according to the HH equation?

1) the concentration of H2CO3 is measured as dissolved CO2 → PCO2

2) PCO2 mmHg x 0.03 = H2CO3 mmol/L

3) Total CO2 = H2CO3 + HCO3-

4) Characteristics:

• Plasma PCO2 ~ 40 mmHg

• Plasma [HCO3-] ~ 24 mmol/L

• pK of bicarb buffer is 6.1

• H2CO3 = 0.03 × 40 mmHg = 1.2 mmol/L

• pH = 6.1 + log [24]/[1.2] = 7.4

What are the RI for:

• pH

• pCO2

• pO2

• HCO3-

• TCO2

• O2

• Base Excess

• pH (7.35-7.45)

• pCO2 (35-45 mmHg)

• pO2 (80-100 mmHg)

• HCO3- (22-26 mmol/L)

• TCO2 (23-27 mmol/L)

• O2 Saturation (94-100%)

• Base Excess 0 ± 2

  • Increases in metabolic alkalosis

  • Decreases in metabolic acidosis