FLUID AND ELECTROLYTE BALANCE

Fluid Balance

• Water Content in Body:
    - average adult weight: 70 kg
    - total body water: 42 L
      - Intracellular Fluid (ICF): 28 L
      - Extracellular Fluid (ECF): 14 L
        - Plasma: 3.5 L
        - Interstitial Fluid: 10.5 L

Electrolytes

• Primary Electrolytes:
    - Na+ (Sodium): Principal ECF cation
    - K+ (Potassium): Principal ICF cation
    - ICF Main Anions: Proteins and phosphates
    - ECF Main Anions: Cl- (Chloride) and HCO3- (Bicarbonate)

• Biochemical Profile Measurements:
    - Serum levels of Na+, K+, urea, creatinine, Cl-, and HCO3- are frequently tested to assess fluid and electrolyte status and renal function.

Water and Sodium Balance

• Water Loss Mechanisms:
    - primarily as urine
    - Obligatory "insensible" losses: losses via skin and lungs

• Control Mechanism:
    - Arg the relationship between water retention and osmolarity is tightly regulated by Arginine Vasopressin (AVP), also known as Anti-Diuretic Hormone (ADH).
      - AVP secretion:
        - Increases with rising osmolality leading to water retention.
        - Decreases with declining osmolality stopping the secretion of AVP.
   

Sodium Regulation

• Sodium in the Body:
    - Concentration range: 135-145 mmol/L
    - Major contributor to serum osmolality (normal plasma osmolality: 275-295 mmol/kg, with approx. 50% attributed to Na+ ions).
    - Sodium intake in western societies: 100-300 mmol/day
    - Sodium excretion primarily through the kidneys, with minor losses through sweat and feces.

Hormonal Regulation of Sodium

• Regulated by two hormones:
    - Aldosterone:
      - Promotes sodium retention in kidneys.
    - Atrial Natriuretic Peptide (ANP):
      - Secreted by cardiocytes in the right atrium.
      - Increases sodium excretion (natriuresis).

Renin-Angiotensin-Aldosterone System (RAAS)

• Components and Mechanism:
    - Renin: Enzyme secreted by kidneys, initiates the RAAS pathway.
    - Angiotensinogen: Secreted from the liver, converted to Angiotensin I by renin.
    - Angiotensin I: Converted to Angiotensin II by Angiotensin-Converting Enzyme (ACE) in lungs.
    - Angiotensin II Effects:
      - Arteriolar vasoconstriction increases blood pressure.
      - Stimulates aldosterone secretion.
      - Increases sympathetic activity and ADH secretion, leading to sodium reabsorption and water retention.
      - Results in increased circulating volume and renal perfusion.
     

Disorders of Sodium Balance

Hyponatremia

• Definition: Measured as sodium concentration.

• Causes:
    - Loss of sodium (e.g., vomiting, diarrhea, burns, Addison’s disease).
    - Water retention from inappropriate ADH secretion (e.g., SIADH following trauma).

• Metabolic Aspects:
    - ECF sodium decrease leads to decreased osmotic pressure.
    - Water shifts from ECF to ICF causing cellular swelling.

• Clinical Symptoms:
    - Nausea, malaise, headache, lethargy, altered consciousness.
    - Severe symptoms (seizures/coma) usually below Na+ concentration < 110-115 mmol/L.

• Signs of Volume Depletion:
    - Hypotension, decreased urine output, decreased skin turgor, dry mucous membranes, increased pulse.

Hypernatremia

• Causes:
    - Water Depletion:
      - Decreased intake (post-op, dysphagia) or excessive losses (diabetes insipidus, sweating).
    - Sodium Retention:
      - Excessive intake (saline infusion), excessive adrenocortical hormones (e.g., Conn’s syndrome).

• Metabolic Aspects:
    - Results in increased Na+, osmotic pressure, and urine concentration.
    - Clinical symptoms: Thirst, oral dryness, loss of skin turgor, weakness, oliguria with concentrated urine.

Potassium Regulation

Potassium Physiology

• K+ Function in Body:
    - Major ICF cation with 2% in ECF.
    - Serum level: 3.5-5 mmol/L.
    - Intake: 30-100 mmol/day (UK).
    - Mostly excreted by kidneys (20-100 mmol/day) with minor fecal losses (~5 mmol/day).

• Regulation of Potassium Levels:
    - Serum K+ remains stable, but shifts in intracellular potassium can cause significant changes in ECF K+ concentration.
    - Insulin Influence: Stimulates K+ uptake into cells.
    - H+ Ion Relation:
      - In acidosis: increased H+ displaces K+ into ECF.
      - In alkalosis: K+ shifts back into cells.

• Function of K+: Essential for excitability of neuromuscular tissues.

Hyperkalemia

• Causes:
    - Renal failure, mineralocorticoid deficiency (Addison’s disease), acidosis, high tissue damage, excessive K+ sparing diuretics/supplements.

• Management and Effects:
    - Cardiac and skeletal muscle impact, primarily causing cardiac effects.
    - Clinical signs: Arrhythmias, tachycardia, ventricular fibrillation, asystole, leading to cardiac arrest.

Hypokalemia

• Causes:
    - Gastrointestinal losses (vomiting/diarrhea), renal losses due to kidney failure, alkaline conditions causing K+ shift to ICF, drug-induced losses (diuretics, corticosteroids).

• Symptoms: Severe muscle weakness, hyporeflexia, arrhythmias.

Calcium Regulation

Calcium Homeostasis

• Abundance: Calcium is the most abundant mineral in the body, with dietary intake averaging 1g/day (25-50% absorption).

• Serum Levels: Normal corrected serum calcium: 2.2-2.6 mmol/L.

• Regulation:
    - Driven by Vitamin D (Cholecalciferol) and PTH.
    - PTH Role: Secreted in response to low calcium, it increases bone resorption, renal reabsorption, and intestinal absorption of calcium.

Vitamin D Metabolism

• Sources:
    - Skin (exposed to sunlight), diet

• Functions:
    - Increases gut calcium absorption, promotes bone health.

Calcium Functions

• Body Functions:
    - 99% found in bone; essential for cellular excitability, muscle contractility, enzyme co-factor.

• Correction Calculation: Total calcium measurement may be affected by serum albumin levels; corrected calcium can be calculated if albumin is low:
    - Corrected Calcium (mmol/L):
      $ext{Total Measured Calcium} + 0.02 imes (40 - ext{Albumin})$

Hypocalcemia

• Causes:
    - Hypoparathyroidism, vitamin D deficiency, renal disease affecting synthesis of active vitamin D.

• Clinical Features: Neuromuscular disturbances (tetany), psychiatric symptoms (depression), management includes calcium and vitamin D supplementation.

Hypercalcemia

• Causes:
    - Hyperparathyroidism, vitamin D overdose, neoplasms, bone diseases.

• Symptoms: Neurological issues (lethargy, confusion), gastrointestinal problems (anorexia, constipation), renal effects (polydipsia, renal stones); try to limit calcium levels below 3.75 mmol/L to prevent cardiac arrest.

Functions of the Kidney

• Key Roles:
    - Regulation of water, electrolyte, and acid-base balance.
    - Excretion of metabolic waste products (urea, creatinine, uric acid).
    - Endocrine functions (secretion of hormones such as renin and erythropoietin).

Assessment of Renal Function

Glomerular Filtration Rate (GFR)

• Estimation Importance:
    - Assessment is critical, especially in drug therapy where renal clearance is vital.
    - GFR measured as plasma clearance of a marker.

• Ideal Markers:
    - Endogenous (creatinine, urea) or exogenous substances (inulin).
    - Inulin is the gold standard for estimating GFR.

Markers and Their Functions

• Urea:
    - End product of protein metabolism, filtered at glomeruli, indicating renal function.
    - Levels can increase due to catabolism, high protein intake, or GI bleeding.

• Creatinine:
    - Byproduct of muscle metabolism, primarily filtered by glomeruli, with constant production based on muscle mass.
    - Reference range: 40-130 µmol/L, varies between individuals, especially by body size.
    - Rising serum creatinine typically indicates decreasing GFR.

GFR Calculations

• Several formulas exist for estimating GFR based on serum creatinine and urine creatinine concentrations.

• Calculation Formula:
    $ext{GFR (ml/min)} = rac{ ext{Curine} imes ext{Vurine}}{ ext{Cserum}}$
    - where Curine = urine creatinine concentration, Vurine = volume of urine collected, Cserum = serum creatinine concentration.

• Cockcroft and Gault Equation:
    $ext{GFR} = A imes (140 - ext{age (years)}) imes ext{weight (kg)} ext{ / Serum Creatinine (µmol/L)}$
    - where A = 1.23 for males, 1.04 for females.

Limitations of Creatinine Clearance

• Influences on creatinine production lead to overestimation of GFR in malnourished, elderly, or amputee patients.

• Best practice: use urine collection for improved accuracy in atypical populations.

Grades of Renal Impairment

Definitions and Classifications

• 
  
  

• eGFR and CrCl:
    - CrCl serves as a surrogate for GFR.
    - eGFR normalized to body surface area.
    - Use of CKD-EPI or MDRD formulas for estimation.

• 
  
  

• CKD Classification Based on GFR:
  
  

  
  

  Degree of Impairment	eGFR (mL/min)	Categorization
  Stage 1	>90	Normal
  Stage 2	60-89	Mild increase
  Stage 3	30-59	Moderate-to-severe
  Stage 4	15-29	Severe decrease
  Stage 5	<15	Established renal failure
  Questions for Review

  1. List TWO conditions causing hypernatremia with mechanisms.

  2. Name TWO emergency medications for severe hyperkalemia.

  3. Estimate creatinine clearance for a 60 kg, 80-year-old male with serum creatinine of 220 µmol/L.

  4. Calculate renal function for Mr. X (56, 70kg, 5ft 3in, creatinine 200µmol/L).

  5. Apply GFR calculation using:
        - GFR = A x (140 - age) x weight / Serum Creatinine where:
          - A = 1.23 for males, 1.04 for females.
          - Ideal Body Weight calculations provided.

  References

  • Clinical Biochemistry – Allan Caw et al.

  • Saunder’s Pocket Essentials of Clinical Medicine – Allan Ballinger and Stephen Patchett

  • Clinical Pharmacokinetics – Soraya Dhillon and Andrzej Kostrzewski

  • BNF – latest edition