1. Disorders of extracellular volume
2. Disorders of water metabolism
3. Disorders of potassium metabolism
4. Disorders of Calcium and Phosphate metabolism
5. Acid-Base balance and disorders

• Cations 153 mEq/l: Na+ 144, K+ 4,5, Ca2+ 2,5, Mg2+ 2,0
• Anions 153 mEq/l: Cl- 101, HCO3- 26, Protein anions 16, other 10

• AG = Na+ – (Cl- + HCO3-)
• Normal range: <12 mEq/l
• Anions not assessed in routine practice: Protein, Organic acid, Phosphate, Sulphate

• Osmolality – a measure of the number of dissolved particles per unit of water in serum
• CALCULATED:
  Total osmolality = 2[Na+(mmol/l)] + [glucose(mmol/l)] + [urea(mmol/l)]
  Total osmolality = 2[Na+(mmol/l)] + [glucose (mg/dl)/18] – [BUN (mg/dl)/2,8]
  Estimated in pts with normal renal function and no DM: Osmolality = 2[Na+(mmol/l)] + 10
• MEASURED:
  Measured with the use of osmometer.

• Normal range: 280-295 mmol/kg H2O
• hypoosmolality – < 280 mmol/kg H2O
• hyperosmolality – > 295 mmol/kg H2O

hypernatremia hyperglicaemia, DEHYDRATION --> reales ADH--> collecting tubules to reabsorb water

• BP, HR, Jugular veins, Skin turgor, Eye bulb turgor
• Mucous membranes (dry if dehydrated)
• In hospital ward: 24 hrs fluid balance/chart, Weight, CVP (6-10 cm H2O)

• Average body sodium content = 4200 mmol
• 91% of sodium in ECF.
• Average Na concentration in ECF = 140 mmol/l
• Average Na concentration in ICF = 10-20 mmol/l
• Daily sodium intake = 2-4 g (80-160 mmol)
• Excretion: 95% urine, 4,5% digestive tract, 0,5% skin/sweat

• Urine Na concentration = 10-400 mmol/l
• Excretion regulation: GFR, Aldosterone, Natriuretic peptides: ANP, BNP

• Distribution in the Body:
  Total body K+ stores: 50-55 meq/kg body weight (3500-4000 meq K+ total)
  Extracellular fluid compartment: 2% [K+] = 3.5-5.0 meq/L (50-100 meq K+)
  Intracellular fluid compartment: 98% [K+] = 120-150 meq/L
  Large cellular K+ (and Na+) concentration gradients are maintained by the Na,K-ATPase

• Hypokalemia hyperpolarizes excitable tissues
• Hyperkalemia depolarizes excitable tissues

• External Balance: The regulation of total body potassium content through alterations in potassium intake (e.g. dietary) and excretion (e.g. renal, GI)
• Internal Balance: The regulation of the distribution of potassium between intracellular fluid (ICF) and extracellular fluid (ECF) compartments

• Dietary intake = 50-150 meq/day (3-9 grams KCl/day)
• IV KCl, hyperalimentation, drugs
• Blood products

• Proximal tubule:
  • Majority of solute and H2O transport
  • Passive processes
  • 65% filtered K+ load

• Thick ascending limb
  • 25% filtered K+ load
  • Active + passive processes
  • Na-K-2Cl cotransporter

• Cortical and medullary collecting ducts
  • Intercalated cells (Type A + Type B)
  • Active process
  • H-K-ATPase

• Insulin stimulates the cellular uptake of potassium via an increase in Na+,K+-ATPase activity
• Insulin and potassium are components of a regulatory loop
  High splanchnic K+ concentration stimulates pancreatic insulin secretion
  Insulin stimulates K+ uptake by the liver and muscle returning serum [K+] to normal

stimulate the cellular uptake of potassium via 2- adrenergic receptors by increasing Na+,K+-ATPase activity

• Changes in extracellular pH produce reciprocal shifts in H+ and K+ between extracellular and intracellular fluid compartments
  Metabolic acid-base disturbances have a greater effect than respiratory disturbances
  Metabolic acidoses due to organic acids (ketoacidosis, lactic acidosis) have smaller effects than do acidoses due to mineral acids

• Acidemia: K+ out, H+ in
• Alkalemia: K+ in, H+ out

• Increases in plasma tonicity --> fluid shifts from the intracellular to the extracellular compartments and K+ exits the intracellular compartment along with water via solvent drag

• Plasma [K+] > 5.0
• may be the result of disturbances in external balance (total body K+ excess) or in internal balance (shift of K+ from intracellular to extracellular compartments)

• Disorders of External Balance:
  Decrease Renal K+ excretion, Excessive K+ intake, Acute & chronic renal failure, Decrease Distal tubular flow, Distal tubular dysfunction, Mineralocorticoid deficiency

• Disorders of Internal Balance:
  Insulin deficiency, B2-Adrenergic blockade, Hypertonicity, Acidemia, Cell lysis

• result primarily from the depolarization of resting cell membrane potential in myocytes and neurons
• Cardiac toxicity: ECG changes, Cardiac conduction defects, Arrhythmias
• Neuromuscular changes: Ascending weakness, ileus

• Peaked T-wave, Wide QRS Complex, Shortened QT Interval, Prolonged PR Interval, Further Widening of QRS Complex Absent P-Wave, Sine-Wave Morphology (e.g. Ventricular Tachycardia)

• Multi drug treatment, i.e. Cardiology patients:
  ACEI &/OR ARB, ß blockers, Potassium sparing diuretic (Spironolactone), Potassium supplement
  

• Membrane Stabilization: IV calcium
• Internal Redistribution: IV insulin (+ glucose), ß-adrenergic agonist (albuterol inhaled)
• Enhanced Elimination: Kayexalate (sodium polystyrene sulfonate) ion exchange resin, Loop diuretic, Hemodialysis

• Glucose : insulin - 3 : 1
• 500 ml 5% glucose = 5 x 5 = 25 g glucose + 8 j short acting insulin
• 100 ml 40% glucose = 40 g glucose + 14 j short acting insulin

• Plasma [K+] < 3.5
• may result from disturbances in external balance (total body K+ deficiency) or internal balance (transmembrane K+ shifts)

• Inadequate dietary intake (Malnutrition),
• Increased extrarenal K+ losses:
  GI: Diarrhea, Enteric fistulas
  Cutaneous: Burns

• Hyperreninemia– Renin excess (renal artery stenosis, renin-secreting tumor)
• Primary hyperaldosteronism (Conn’sSyndrome) – Mineralocorticoid excess (adrenal hyperplasia, tumor)
• Cushing’s syndrome – Glucocorticoid excess (exogenous, pituitary, adrenal)
• Congenital adrenal hyperplasia – Enzymatic defects in cortisol biosynthesis (excess aldosterone precursors)

– Insulin excess
– Catecholamine excess
• Myocardial ischemia/infarction
• Delirium tremens
• Pharmacologic agents
– Alkalemia
– Cell proliferation
• Rapidly proliferating leukemia or lymphoma

Cardiac – EKG changes – Arrhythmias
Smooth muscle – Hypertension – Ileus
Skeletal muscle – Weakness – Rhabdomyolysis
Metabolic – Glucose intolerance – Growth retardation
Renal – Increased renal ammoniagenesis – Nephrogenic diabetes insipidus

• Potassium Replacement – Oral or IV (kcal)
• Potassium-sparing diuretics
  – ENaC sodium channel inhibitors • Amiloride, triamterene
  – Mineralocorticoid antagonists • Spironolactone