L4 - Water and Electrolytes Flashcards
Estimate of the water content in the human body?
- ~60% total body mass ~ 42 L
- 2/3 ICF ~ 28 L
- 1/3 ECF:
- 75% interstitial (water that baste cells) ~10.5 L
- 25% plasma (in blood vessels, intravascular compartments) ~ 3.5 L
Routine Biochemical Testing assesses
Plasma (ECF)
Imbalance in Total Body Water content initially reflected in…
ECF
Adults: Water intake and Urine output daily?
Intake of 1.5 – 3.0 L of water daily to maintain fluid balance
Urine Output 0.8 – 2.0 L of water daily
Primary organ for regulating body water?
Kidney
How is compartmentalization maintained?
- ICF and ECF: separation by selectively permeable cellular plasma membrane
- Intravascular fluid and ISF: separation by capillary endothelium cells
Electrolyte Distribution?
- Plasma and interstitial fluid are somewhat similar
- ICF concentrations of electrolytes differ from ECF
Major ECF (plasma and interstitial) ions?
- Na+
- Cl-
- HCO3-
(Salty outside cells)
Major ICF ions?
- K+
- Mg2+
- Protein-
- Minor components not listed (e.g. Mg2+ ,HPO4^2-, SO4^2-, etc)
Electroneutrality?
[cations] = [anions]
Osmolytes?
Electrolytes contribute to osmotic pressure
What is Osmotic Pressure?
Pressure exerted on either side of a membrane due to differences in the total molar concentrations of solutes dissolved in solutions
• Governs the movement of water
• Dependent on the [Osmolytes]
Oncotic Pressure
Osmotic pressure induced by Albumin that cannot easily move out of capillary vessel
Albumin attracts ions and electrolytes => water tries to enter blood vessel => pressure from ECF exerted on the vessel
What maintains the high water content in tissue?
The osmotic force created by the high [Na+] (remember high Na+ outside vs. inside cells)
- allowing tissue to withstand pressures that can exceed 20,000 mm Hg during exercise
Osmolality?
Concentration of solutes expressed per mass of solvent
• Thermodynamically more appropriate term as mass, unlike volume, is independent of the temperature;
• unit = Osmol/Kg
Hyperosmolality
hyperglycemia, uremia, hypernatremia (e.g. dehydration, diabetes insipidus, uncontrolled diabetes mellitus, renal failure)
Osmolarity?
Concentration of solutes expressed per volume of solvent
• Unit = Osmol/L
How to measure Osmolality?
Measured by Osmometer: Freezing point depression (colligative property)
- Principle behind using salt to melt ice (lowers freezing point to <0°C)
- 1 mole of solute depresses freezing point of H2O by 1.86 °C
Estimated Osmolarity?
≈ 2 × [Na+] in mM + [Glucose] in mM + [Urea] in mM
Serum Measured Osmolality (mOsmol/ kg H2O)
Measured osmolality is looking at other number of metabolites that is not factored into the calculation
Serum Calculated Osmolality (mOsmol/kg H2O)
Simply examines: Sodium, Glucose and Urea
Serum Osmolality Gap?
Serum Osmolal Gap = Measured Osmolality – Calculated Osmolarity
* assume osmolality ~ osmolarity
• Determines osmotically active solutes that maybe unaccounted by estimation
e.g., Methanol or Anti-freeze (ethylene glycol) ingestion (poisoning)
• Gold standard test: gas chromatography (not routinely available)
Large O.G. = concern
How useful is the Osmol Gap calculation?
O.G > 10 to 14 mmol/kg maybe useful to suggest presence of toxic alcohol or other osmolyte that is accumulating.
Toxic Alcohols that elevates OG
Ethylene Glycol
Isopropanol
Methanol
Propylene Glycol
Other Scenarios where OG is elevated
Ethanol-related
Renal Failure –uremic acid
Shock –lactic acid
Diabetic Ketoacidosis –Beta hydroxybutyric acids
Other
Volemias…
…are assessments based on observation of the patient, not based on any laboratory measurements
Hypervolemia?
increased fluid
• Edema
Hypovolemia?
decreased fluid
• Dry mucous membranes
• Decreased skin turgor (skin tents up upon pinching)
Euvolemia?
normal fluid status (appearance on physical exam)
What are the 2 Disorders of Sodium Homeostasis?
Hyponatremia (low sodium state) vs Hypernatremia (high sodium state):
• Excessive loss, gain, or retention of Na+
• Excessive loss, gain, or retention of H2O
• Symptoms are due to changes in osmolality
What is Hyponatremia?
(low sodium state) decreased plasma Na+, < 135 mmol/L
• Nausea/headache
• Generalized weakness
• Mental confusion (<120 mmol/L)
• Seizures
Symptoms are due to changes in osmolality
Hyponatremic Classification; What are the 2 classes of Hyponatremia (include sub-types)?
Decreased Plasma Osmolality (Hypo-osmotic)
- Hypovolemic hyponatremia (Depletion) - low water volume
- Hypervolemic hyponatremia (Dilution) - high water volume / fluid gain → dilute Na+
- Euvolemic hyponatremia
Increased Plasma Osmolality
1.Hyperosmotic Hyponatremia
What are the 3 Etiologies of Hyponatremia? (Decreased Plasma Osmolality)
- *1. Hypovolemic hyponatremia** – fluid loss → Na+ goes away with the fluid loss
- Renal loss
- Extrarenal loss
- *2. Hypervolemic hyponatremia** – fluid gain → evidence of swelling and high blood pressure
- Cirrhosis
- Heart failure
- Nephrotic Syndrome
- *3. Euvolemic hyponatremia** - can’t tell; have to base on biochemical measurement
- Polydipsia
- SIADH
- Adrenal Insufficiency
- Hypothyroidism
What are 2 underlying causes of Euvolemic Hyponatremia?
Primary polydipsia: Excess water consumption
• Seen in patients with hypothalamic lesions
• Psychogenic polydipsia: excessive drinking in psychiatric patients
• Polyuria (large volumes of urine production) -> maintain euvolemic state
Syndrome of inappropriate anti-diuretic hormone (SIADH)
What is SIADH (contributes to Euvolemic Hyponatremia) and what causes it?
Syndrome of inappropriate anti-diuretic hormone
Causes: Sustained ADH release
- CNS Based: Brain Tumor, Infection (e.g.meningitis)
- Drugs: anticonvulsants, antiparkinsonian, antipsychotics, antipyretics, antidepressants, ACE Inhibitors
How does ADH (Arginine Vasopressin) contributes to the Regulation of Water (osmolality)?
In the Hypothalamus: Osmoreceptors detect changes in serum osmolality
• When plasma osmolality > 280 mOsm/kg (too high) ⇒ threshold for ADH release
Main regulator of ADH release by stimulation of Pituitary Gland (elevated plasma osmolality activates osmoreceptors)
→ Posterior Pituitary: secretes ADH (AVP)
→ Kidney: ADH acts on collecting ducts (Vasopressin-2 receptors)
→ leading to increased water reabsorption and decreased water excretion
What is Hypervolemic Hyponatremia (Decreased Plasma Osmolality) and what are the possible causes?
Dilutional Hyponatremia – fluid overload
• Excess water retention → Edema
• Nephrotic Syndrome → hypoalbuminemia (Albuminuria, hyperlipidemia)
• Cirrhosis
• Advanced Kidney Failure: Excess water retention > Sodium retention (decreased filtration & excretion)
• CHF - Congenitive Heart Failure: Increased ECF, Decreased (effective circulating) Blood Volume
• Summary: ECF is increased ⇒ circulating blood volume decreased
Why is the Renin-Angiotensin-Aldosterone System – Important in Heart-Failure? (Think what effect does it have on blood flow)
Kidneys sense decreased perfusion (not enough blood circulating) & try to increase blood volume
How?
Renin → Angiotensin I → Angiotensin II → has 2 effects:
1) Vasoconstriction – narrowing of blood vessel
2) Aldosterone release
• Increases Na+ reabsorption in kidneys → Increase blood volume
• Decrease in osmolality sensed by baroreceptors triggers ADH release
- Increased vasoconstriction + increased blood volume raises the blood pressure
- Rx: Help with ACE inhibitors or ARBs (Angiosstensin Receptor blockers)
What is Hypovolemic Hyponatremia (Decreased Plasma Osmolality) and what are the underlying causes?
- State of Low osmolality, Low sodium
- Depletional Hyponatremia
- Excessive loss of Na+, often accompanied by loss of ECF water
- Renal Causes: when [urine Na+] > 20mmol/L (caused by Diuretics, Nephropathies or Polycystic Kidney Disease)
- Extrarenal causes of volume loss (e.g. sweating, vomiting, diarrhea; if [urine Na+] < 20mmol/L)
Intravenous (IV) Solutions for Hypovolemic patients
**Check image in lecture**
What is Hyperosmotic Hyponatremia (Increased Plasma Osmolality)?
Increased osmolyte (glucose, urea) in plasma
• Extracellular shift of water (out of cells into ECF) or Intracellular shift of Na+ to maintain osmotic balance
• E.g., severe hyperglycemia (Na+ decreased ~1.6 -2.4 mmol/L for every 5.6 mmol/L increase in glucose above 5.6 mmol/L) - (Hyperglycemic Hyperosmolar State → can lead to coma or death)
• Patients maybe asymptomatic (until [Na+] < 120 mmol/L)
What are the 2 classes of Hypernatremia?
Hypervolemic Hypernatremia and Hypovolemic Hypernatremia
Hypervolemic Hypernatremia
Increase in water volume and Na+
• Typically, from administering hypertonic solutions (saltier than physiological - IV during operations)
• Primary hyperaldosteronism (Conn’s syndrome) from tumor or hyperplasia
- Aldosterone > increased Na+ absorption > water follows Na+ > retain water AND Na+
What is Hypovolemic Hypernatremia?
More water loss than Na+ sodium loss
- Renal losses: renal disease or diuretics (Urine [Na+] > 20 mmol/L)
- Extrarenal losses: Sweat, stool, fluid shifts after burns or surgery
Euvolemic Hypernatremia?
- Hypodipsia: decreased water intake (e.g. hypothalamic lesion)
- Diabetes Insipidus
ADH deficiency – Diabetes Insipidus (DI)
Decreased ADH (secretion or loss)
- Decreased water reabsorption
- Increased and dilute urine output
- Concentrated serum (increased osmolality, hypernatremic)
Central DI?
Intracranial (tumor, post-neurosurgery, head trauma)
Nephrogenic DI?
Originates in the kidneys (sensitivity to ADH is lost) - loss of receptors
• E.g. polycystic kidney disease, nephrotoxicity from drugs
K+ :major ICF cation?
- Neuro-muscular excitability
- Heart rhythm and contraction
- Acid – Base Status
*Check figure on slide 33*
Potassium Excretion Peaks at Noon
Multiple patients receiving four identical meals every 6 hours
- Normal K+ diet (100 mmol/day) first 2 days
- High K+ diet(400 mmol/day) next 6 days
- Normal K+ diet (100 mmol/day) next 2 days
Rapid K+ adaptation by Kidney occurs in response to either an increase or a decrease in K+ intake.
- circadian rhythm occurs despite evenly spaced meals every 6 hours during a 24-hour period.
Normal interval of plasma for Potassium (K+)
[K+] = 3.5 – 5.0 mmol/L
• Tight regulation
Remember K+ is abundant in ICF; should not have high concentration in plasma (ECF)
Hyperkalemia and Decreased Urinary Excretion?
High K+ in blood
plasma [K+] > 5.0 mmol/L
Decreased urinary excretion due to:
- Renal failure - decreased filtration (sodium NOT reabsorbed > secreted)
- Hypoaldosteronism - Decrease [aldosterone] or decreased response to aldosterone
(Aldosterone increases Na+ reabsorption by stimulation of epithelial sodium channels in exchange for K+ and H+ i.e. Na+ into blood and K+ and H+ from blood out to kidney lumen)
- Without aldosterone Na+ is not reabsorbed and K+ remains in blood
*slide 37*
Hypokalemia
Low K+ in blood
plasma [K+] < 3.5 mmol/L
- Increased urinary (renal) or GI loss
- Vomiting resulting in acid loss from stomach → alkalosis
- Renal loss: hyperaldosteronism (e.g.adrenal adenomas) - too much aldosterone → increased Na+ reabsorption → too much K+ exchanged/leaving blood - Shift of K+ from ECF to ICF
- Insulin excess (excess treatment with insulin or insulinoma) - Decreased Intake (rare)
Anion GAP
= [Na+] – [HCO3-] – [Cl-] ≈ 3 – 12 mmol/L
Abnormally high value of Anion GAP
MUDPILES
• Methanol ingestion
• Uremia of renal failure
• Diabetic Ketoacidosis
• Paracetamol (Acetaminophen) Toxicity
• Isoniazid, iron toxicity, ischemia
• Lactic acidosis
• Ethylene glycol poisoning
• Salicylates intoxication
What stimulates ADH (Arginine Vasopressin) Release?
thirst → + water intake → elevated plasma osmolality (above 280 mOsm/kg)
→ activates Osmoreptor in the Hypothalamus
Where is ADH secreted?
Posterior Pituitary Gland
What organ does ADH act on to regulate water balance? Name the receptors and downstream pathway.
Kidney: ADH acts on collecting ducts (Vasopressin-2 receptors)
ADH (Arginine Vasopressin) binds Vasopressin-2 receptor
→ activates G-alpha subunit of AC6
→ increased cAMP production (ATP-dependant)
→ activates protein kinase → activate transcription factors (nucleus) → Increased aquaporin 2 (AQP2) transcription
→ activated protein kinase → AQP2 phosphorylation → exocytic insertion to luminal membrane → increased water reaborption
What is the net effect of ADH (Arginine Vasopressin) presence in the principal cell of Kidney’s Collecting Duct?
- increased transcription of AQP2
- redistribution of aquaporin-2 to the luminal membrane
In the presence of vasopressin, water enters the principal cell from the lumen through aquaporin-2 (inside of the CD) and exits to the interstitium through aquaporin-3 and aquaporin-4 (into interstitial space)
→ increased water reabsorption
What happens when we have SIADH and how does lab test help?
Excessive free water retention
- How does lab test help?
- Diagnosed when hyponatremia (<135 mmol/L) and hypo-osmolality(<275-280 mOsm/kg) present with concentrated urine
- [Urine sodium] > 40 mmol/L (thisisabnormal)
- THG: Volume expansion decreases Na+ reabsorption by kidney
Describe how Renin is converted into Aldosterone?
Renin (kidney detects decreased perfusion) → converts Angiotensinogen (from liver) → Angiotensin I → Angiotensin II (detected by adrenal glands) → Aldosterone (from adrenal glands)
Hyperkalemia – Increased movement of K+from ICF to blood stream
Increased movement of K+from ICF to blood stream
• Cellular breakdown (Pseudohyperkalemia–RBC lysis during blood draw)
> due to Tumor lysis after chemotherapy; Crush injuries/trauma
- Metabolic Acidosis
- Insulin deficiency/resistance (Insulin promotes dietary K+ into cells)
- Beta-blockers (medications to reduce blood pressure)
