Acid-Base Disorders Overview

Acid-Base Disorders

• Metabolic Acidosis

  • ↑ Production/ingestion of H+ or loss of HCO3-
  • Causes: High anion gap metabolic acidosis (lactic acidosis, ketoacidosis, renal insufficiency, exogenous acids), normal anion gap metabolic acidosis (renal tubular acidosis, GI loss of HCO3-)
  • Compensation: Decreased pCO2
  • pH: ↓ (may be in the reference range with complete compensation)
  • pCO2: ↓
  • HCO3-: ↓

• Metabolic Alkalosis

  • Loss of H+ or ↑ Production/ingestion of HCO3-
  • Causes:
    • Chloride-responsive (normal urinary chloride): vomiting, nasogastric suction, hypovolemia, loop or thiazide diuretics
    • Chloride-resistant (elevated urinary chloride): hyperaldosteronism, Cushing syndrome
  • Compensation: ↑ pCO2
  • pH: ↑ (may be in the reference range with complete compensation)
  • pCO2: ↑
  • HCO3-: ↑

• Anion Gap: difference between primary measured cations (Na+, K+) and primary measured anions (Cl-, HCO3-) in serum

Symptoms of Acid-Base Disorders

• Metabolic Acidosis: Weakness, fatigue, headache, confusion, rapid breathing (Kussmaul breathing), coma
• Metabolic Alkalosis: Weakness, fatigue, nausea, vomiting, muscle cramps, tetany, coma

Hyperuricaemia

• Definition: Elevated blood uric acid (>6.8 mg/dL)
• Source: Uric acid is derived from purine nucleotides: AMP, GMP
• Urate Form: Mostly occurs in its ion form (urate)
• Causes:
  • Dietary: Meat, organs, fish, beans, sweetbreads, yeast, beer, sweetened soft drinks (high fructose corn syrup)
  • Medical Conditions: Chronic kidney disease, hypertension, hypothyroidism, insulin resistance
  • Medications: Diuretics (thiazides, loop diuretics)
  • Genetic:
    • Primary gout
    • Inflammatory arthritis
  • Other: Iron overload, excess alcoholic beverages, obesity

Pathophysiology of Hyperuricaemia

• Urate Precipitation: When the solubility of urate exceeds its normal threshold (>6.8 mg/dL), monosodium urate (MSU) crystals can form and lead to gout.

  • Solubility: Uric acid has a relatively low aqueous solubility, so even a modest increase in serum concentration can elevate the risk of MSU crystal formation and precipitation, especially in joints and urine.

• Body's Inability to Handle Urate Load:

  • Overproduction: Too much uric acid is produced, overwhelming the kidneys/GIT to adequately excrete it.
  • Underexcretion: Insufficient amount of uric acid is excreted or egested.

• Consequences: Heart disease, diabetes, kidney disease

Signs & Symptoms of Hyperuricaemia

• Asymptomatic: Majority of patients
• Symptomatic: Approximately 33% experience symptoms:
  • Crystals: MSU crystals form in and around joints and kidneys.
  • Inflammation & Pain: White blood cells attack the crystals, causing inflammation and pain.
  • Gout (gouty arthritis):
    • Redness and swelling (inflammation)
    • Joint stiffness
    • Severe joint pain
    • Difficulty moving affected joints
    • Mis-shapen joints
  • Tophaceous gout: Hard lumps (tophi) formed by uric acid crystals under the skin, around joints, and in the top ear curvature.

Renal (Kidney) Diseases

• Kidney Functions:

  • Urine Production & Excretion: Regulates waste excretion, acid-base balance, fluid & electrolyte balance.
  • Erythropoietin Production: Stimulates red blood cell production.

• Sepsis:

  • Imbalance in the body's response to chemicals (sepsis) can damage multiple organs.
  • Chemical & humoral mediators released during sepsis contribute to pro-inflammatory response and systemic vasodilation.
  • This causes decreased systemic pressure, stimulating the sympathetic nervous system.
  • Consequences:
    • Renal artery constriction
    • Decreased filtration
    • Decreased excretion
  • Sepsis can lead to kidney damage:
    • Obstruction: Leads to hypoperfusion of the kidneys.
    • Hypoperfusion: Leads to ischemia, hypoxemia, azotemia (excess blood nitrogenous wastes), reduced GFR, electrolyte imbalance, metabolic acidosis, and kidney damage.

Pathophysiology of Acute Renal Failure

• Intra-renal Failure: Problems within the kidneys themselves (e.g., glomerulonephritis, tubular necrosis) damage the glomerular blood vessels, tiny tubules, and affect renal blood flow.

  • Prolonged Ischemia: Can lead to kidney damage and intrinsic renal azotemia.
  • Blood/Fluid Loss: Leads to hypotension and ischemia, resulting in toxic free radical generation, swelling, injury, and necrosis.

• Post-renal Failure: Obstruction in the urinary tract (e.g., kidney stones, tumors) prevents outflow of urine.

  • Consequences: Azotemia, build-up of pressure in the kidney nephrons, damage to renal tissue, shutdown of nephrons.

Chronic Renal Failure (CRF)

• Definition: Progressive loss of nephron function.
• Damage: Irreversible damage to about 75% of nephrons.
• Current Term: Chronic Kidney Disease (CKD)
• Onset: Usually slow and asymptomatic.
  • GFR: Progressive reduction in glomerular filtration rate (GFR) to approximately 10% of normal function (12.5-20 ml/min).
  • End-Stage Renal Disease (ESRD): GFR falls below 5% (6.25-10 ml/min).

Classification of Chronic Kidney Disease

• Based on GFR and albuminuria levels.

Causes of Chronic Renal Failure

• Main Causes of End-Stage Renal Disease (ESRD):
  • Diabetes mellitus (28%)
  • Hypertension (25%)
  • Glomerulonephritis (21%)
  • Polycystic kidney disease (4%)
  • Other/unknown (22%)
• Other Causes:
  • Autoimmune diseases (e.g., lupus, IgA nephropathy)
  • Genetic diseases (e.g., hereditary nephritis - Alport syndrome)
  • Nephrotic syndrome
  • Urinary tract problems

Pathophysiology of Chronic Renal Failure

• Adaptive Physiology: Over time, the body creates compensatory mechanisms to maintain kidney function.
  • Hyperfiltration: Remaining nephrons work harder to filter blood.
  • Hypertrophy: Remaining nephrons grow larger to compensate for lost nephrons.
• Histopathologic Changes: As insult continues, histological changes occur:
  • Distortion of glomerular architecture
  • Abnormal podocyte function
  • Disruption of filtration
  • Sclerosis (scarring)