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)

This quiz covers the fundamentals of acid-base disorders, specifically focusing on metabolic acidosis and alkalosis. Participants will learn about the causes, compensation mechanisms, and key biochemical parameters involved. Test your understanding of these essential concepts in biochemistry and physiology.