Alcoholic Cirrhosis and Fluid Balance

Body Fluid Composition

• Water is the most abundant component of the human body.
• Water amount is a function of adipose tissue.
• Water is 60% of adults body weight.
  • Men: 55-65%.
  • Women: 45-55% due to more adipose tissue and less muscle mass.
  • Infants: 70% body weight is water.

Total Body Water (TBW)

• TBW is distributed in two compartments:
  • Intracellular Fluid contains 2/3 of TBW, which is 40% of body weight.
  • Extracellular Fluid contains 1/3 of TBW, which is 20% of body weight.
• Plasma is 4% of body weight and inside the blood vessels.
• Interstitial fluid bathes cells and lymph and is an ultrafiltrate of plasma, accounting for 12% of body weight.
• Transcellular fluid include CSF and Intraocular Fluid.
  • Transcellular fluids are separated from blood across capillary endothelium/epithelium.

TBW in 70 Kg Male

• TBW is equal to 42 Liters given by the calculation 70 Kg x 0.6.
• ICF makes up 28 Liters calculated by 70 Kg x 0.4.
• ECF makes up 14 Liters calculated by 70 Kg x 0.2.
  • Interstitial fluid: 8 Liters (70 x 0.12).
  • Plasma: 3 Liters (70 x 0.04).

Effective Circulating Volume (ECV)

• ECV is apart of ECF effectively perfuses tissues and stimulates the receptors.
• ECV changes directly correlate to changes in ECF under normal conditions.
• ECF increases in disease states such as CHF but ECV decreases in disease states (CHF/Cirrhosis/Nephrosis/Burns).
• The body responds to changes in ECV by varying renal Na+ excretion:
  • increase in ECV leads to an increase in renal Na+ excretion.
  • decrease in ECV leads to a significant decrease in renal Na+ excretion.

Movement of Body Fluids

• Capillaries allow free movement of fluid, ions, and water.
• Hydrostatic pressure pushes fluid out.
• Colloid oncotic pressure pulls fluid in.
• Net fluid movement determined by balance between hydrostatic and colloid oncotic pressure.

Osmotic Equilibrium

• Osmolality is the ratio of solutes per Kg of solvent.
• Normal range 290 ± 10 mOsm/Kg.
• Plasma Osmolality is calculated by: 2 [SNa+] + Glucose/18 + BUN/2.8.
• Osmolality of ICF = ECF = Plasma
• Plasma has osmolality about 1 mOsm/Kg > ISF due to Plasma proteins.

Movement of Body Fluids: Osmotic Equilibrium

• Control: Osm = 280 mEq/L for Intracellular and Extracellular Fluid with water equilibrium.
• Addition of 210 mM NaCl to ECF raises Extracellular Osm to 290.
• Adding 1.5 L Water to ECF lowers ECF osm to 270, while adding 1.5 L Normal NaCl to ECF raises volume but osm remains at 280.

Fluid Balance

• Intake: water, food, beverages.
• Output: Urine, feces, insensible losses (breathing, sweat and evaporation).

Regulation of Body Water

• Regulation works through ADH (AntiDiuretic Hormone, Arginine vasopressin (AVP)).

• Increased blood osmolality.

  • Blood is too concentrated.

• Decreased circulating blood volume.

• Stimulation causes hypothalamic osmoreceptors.

• ADH is released causing a decrease in renal water excretion.

• Stimulation of thirst response causes increased drinking.

• Overall, water volume within the body increases.

AVP Regulated Water Transport

• AVP binds to VR receptor.
• Protein Kinase A synthesis occurs.
• AQP2 exists from Exocytosis and Endocytosis.

Isotonic Alterations

• Volume of fluid changes, but numbers and types of electrolytes remain at normal levels.
• Loss leads to volume depletion (hypovolemia).
  • Hemorrhage.
  • Severe wound drainage.
  • Excess sweating.
  • Burns.
  • Third spacing.

Hypovolemia

• Fluid is lost from blood vessels.
• Symptoms:
  • Decreased blood pressure.
  • Increased heart rate.

Hypervolemia

• Excess body fluid occurs.
• Excessive IV fluids
• Overproduction of aldosterone.
• Drugs like Cortisol.
• Increased ECF volume leads to
  • Weight gain (fluid weight).
  • Diluted urine.
  • Increased blood pressure.
  • Edema.

Edema

• ECF Isotonic Volume Excess is an accumulation of isotonic fluid in interstitial space (increased ISF).
• Forces that favor increased ISF also favor edema.
• Increased CHP if present in chronic hypertension, venous obstruction, and water retention.
• Decreased COP result of not enough proteins/cells in the blood.
  • Causes may be protein synthesis disorders of liver or losses (kidneys, GI).
• Increased capillary permeability may come from trauma and inflammation.
• Decreased lymph drainage may come from blocked lymph node or surgical removal of lymph vessels.
• Clinical features:
  • Pitting.
  • Weight gain (water weight).
• Treatment:
  • Treats underlying conditions.
  • Fluid restriction.
  • Increase oncotic pressure by administration of Colloids like Plasma/Albumin..
  • Use Diuretics.

Ionic Composition of Body

• Electrolytes consist of Cations and Anions.

  • Cations are positive: Sodium (Na+), Potassium (K+), Calcium (Ca+2), Magnesium (Mg+2).
  • Anions are negative: Chloride (Cl-), Bicarbonate (HCO3-), Phosphate (HPO4-).

• Extracellular Fluid (ECF):

  • Cations: Na+.
  • Anions: Cl-, HCO3-, Proteins.
  • Ionic composition of Plasma and ISF is similar.

• Intracellular Fluid (ICF):

  • Cations: K+, Mg++.
  • Anions: PO4, SO4, Proteins.

Charge and Osmolality

• Body fluids distribution of TBW between ICF and ECF is determined by the number of osmotically active particles in each compartment.
• Na+ and K+ kept in their compartment by Na+-K+ ATPase.
• Sodium salts are the principal ECF osmoles that maintain water in ECF.
• Potassium salts are the principal ICF osmoles that maintain water in ICF.

Cations

• Sodium (Na+).
• Potassium (K+).
• Calcium (Ca++).
• Magnesium (Mg++).

Renin-Angiotensin-Aldosterone

• Angiotensinogen goes from the Liver to Angiotensin I using Renin.

• Angiotensin I goes to Angiotensin II with ACE Enzyme.

• Angiotensin II leads to a decrease in UNaV and an increase in SVR and Aldo.

• Current View of Renin-Angiotensin System (RAS)

  • AGT turns to Angl with Renin.
  • Angl turns to Angll with ACE Enzyme.
  • A-(1-9) turns to A-(1-7) with ACE2.
  • Angll goes to AT1R Vasoconstriction, while A-(1-7) goes to Mas Vasodilation.

Tubular Reabsorption of Na+

• PROX: 60%.
• LOH: 25%.
• DCT: 5-7%.
• CD:3-5%.

Aldosterone

• Aldorestone on the Collecting Tubule leads to an Increase 3Na+ and Decrease 2K+.

ANP

• 28 amino acid polypeptide hormone.
• Mainly secreted by the heart atria in response to stretch.
• Leads to ↑ Renal Na+ excretion and GFR.
• Antagonizes renal vasoconstriction.
• Inhibits renin and aldosterone synthesis.

Atrial Natriuretic Peptide

• ANP leads to ↑GFR.
• ANP leads to decreased 3Na+ and decreased 2K+

Sodium

• Sodium represents about 90% of ECF cations at 60 mEq/Kg of body weight.
• Of total body Sodium, 24% is nonexchangeable in the crystalline phase of bone, with the rest exchangeable.
  • Of exchangeable Sodium, 85% is ECF and 15% is ICF.
• Normal range 135-145 mEq/L in ECF.
• Normally pairs with Cl- and HCO3- to neutralize charge.
• Low in ICF (~10 mEq/L)
• Is the most important ion in regulating water balance.

Electrolyte Imbalances: Sodium

• Hypernatremia: (hypertonic imbalance.
• Plasma Na+ > 145 mEq/L.
  • Too much Na+ or too little water.
  • Most commonly caused by water deficit.
• "Tonicity": Number of solute particles in solution.
  • Hypertonic: high amount if solute.
  • Hypotonic: dilute.
• Characteristics of hypernatremia:
  • Movement of water from ICF to ECF.
  • Cells dehydrate.
  • Overall increase in ECF, at expense of the cell volume.

Sodium Imbalances

Hypernatremia

• Administration of hypertonic IV solutions.
• Oversecretion of aldosterone.
  • Causes edema and hypertension, does not cause hypernatremia unless fluid restriction exists.
  • Aldo Escape
• Loss of pure water.
• Long term sweating with chronic fever.
• Respiratory infection causes Tachypnea/humidify air.
• Diabetes insipidus leads to polyuria.
• Insufficient water ingested.

Hypernatremia: Clinical

• Symptoms:
  • Thirst.
  • Lethargy.
  • Neurological dysfunction (dehydration of brain cells).
• Treatment:
  • Lower serum Na+.
  • Use hypotonic (salt-free (5% glucose) to replace body water; returns Na+ concentration to normal levels.
  • Slowly if chronic.
  • Rapid correction causes Cerebral edema, ICH, pulmonary edema.

Hyponatremia

• Overall Na+ decreased in ECF.
• Two types: depleteional or dilutional.
  • Depletional is too little Na+.
  • Dilutional is too much water which is the most common cause.
• Causes of depleteional hypnoatremia:
  • Diuretics.
  • Chronic vomiting.
  • Chronic diarrhea.
  • Decreased aldosterone levels or resistance.
  • Decreased Na+ intake.

Hyponatremia

• Dilutional causes:
  • Renal dysfunction with hypotonic fluid intake.
  • Excessive sweating leads to increased thirst and excessive pure water intake.
  • Syndrome of Inappropriate ADH (SIADH)
• Treatment:
  • Restrict water (Dilutional).
  • Administer Na+ (Depletional).
  • Slowly if chronic.

Potassium

• Major Intracellular cation and 42 mEq/Kg body weight.
• Almost all is in ICF and readily exchangeable.
• ICF concentration = 150-160 mEq/L.
• Lower in ECF at 3.5 - 5 mEq/L.
• Potassium concentration INSIDE cells approximates Na+ concentration OUTSIDE.
• Na+ concentration INSIDE cells approximates K+ concentration OUTSIDE.

Electrolyte Imbalances: Potassium

• Hypokalemia Characterized by Serum K < 3.5 mEq/L.
• Beware of Diabetes:
• Insulin plays a role in K into the cell.
• Ketoacidosis results in increased H in ECF if unregulated.
  • H enters cells.
  • High ECF contains K lost through urine.
  • Overall leads to Potassium deficit throughout the body.

Potassium Imbalances

Hypokalemia

• Causes:
  • Decreased K intake: Rare.
  • Increased K loss:
  • With chronic diuretics.
  • GI disturbance.
  • Renal losses from hyperaldosteronism and gitelman's.
  • Acid/base imbalance from K out of cells into ECF, then lost through urine.

Hypokalemia: Clinical

• Neuromuscular disorders.

• Cardiac arrest.

• There is maintained Na+/K+ gradient for proper action potentials in neurons/muscles so proper neuron/muscle function.

• Treatment: increase Potassium intake must gradually to avoid abrupt Na+/K+ gradient change.

• ECG changes with Potassium imbalance show:

  • The amplitude of the T waves decreased.
  • Increased amplitude of the U wave.
  • Prolongation of the Q-U interval.
  • Increase in amplitude of the P wave.
  • Prolongation of the P-R interval.
  • Widening of the QRS.

Potassium

• Hyperkalemia characterized by Serum K > 5 mEq/L.

• Renal disease leads to decreased filtration or decreased tubular secretion of K causing hyperkalemia.

• Massive Cell trauma can lead to Hyperkalemia because High intracellular K is released into ECF.

• Insulin Deficiency can result in increased K in blood because Insulin plays a role in K uptake into cells.

• Pseudohyperkalemia/ in vitro hemolysis.

• Hyperkalemia can result from altered aldosterone secretion

  • Addison disease cause deficiency of adrenal hormones. Congenital adrenal hyperplasia (adrenogenital syndrome)

• Treatment includes stabilizes the myocardium with Ca+2, promoting Shift of K into ICF with insulin, bicarbonate, and beta agonists while removing Potassium from body.

• Ca+2 counteracts K+ effects on heart making cell less excitable.

• Shift of K+ into ICF includes insulin (+ glucose), bicarbonate & Beta agonists.

• Increased Removal of K+ from body includes Kayexelate & Dialysis.

• Kayexelate is resin exchanges K+ for Na+ in intestine.

• ECG changes:

  • Increased amplitude of T wave (peaked T waves) with shortened Q-T interval.
  • Widening of the QRS complex and decreased amplitude of P wave with eventual loss of P wave.
  • Sine wave pattern as widened QRS merges with T waves.
  • This leads to ventricular fibrillation and cardiac standstill.

Calcium

• Normal serum level: 8.5 - 10.5 mg/dL.

• Total Calcium++ in serum:

  • Sum of ionized and nonionized components.

• Ionized Calcium++ is the most biological activities of Calcium.

• Nonionized Calcium++ is Ca linked to albumins.

  • Concentration increases by an increase of pH.
  • Complexes to small ligands (citrate, phosphate, sulfate).

• Parathyroid Hormone (PTH):

  • Increases bone resorption by stimulating osteoclasts.
  • Promotes 1,25VitD3 synthesis, renal Ca++ reabsorption, serum Ca++.

• 1,25 (OH)2D3 increases intestinal, renal Ca++ absorption, serum Ca++.

  • Leads to decreased in PTH sercretion.

• Calcitonin: decreases osteoclastic bone resorption and serum Ca++.

Hypercalcemia

• Causes due to Hyperparathyroidism, vitamin D excess, High PTH,
• Increased skeletal mobilization (immobility).
• Clinical symptoms: weakness, depression, cardiac arrest,
• Treatment:
  • Normal saline that increases renal calcium exertion and corrects dehydration.
• Glucocorticoids inhibits synthesis of resorbing agents.

Hypocalcemia

• Hypothyroidism or Vitamin D deficiency can cause Hypocalcemia
• Ca gluconate or CaCL can be prescribed in the form of Ca++ and vitamin D,
• If prescribed orally, 1,25 Vit D3 can be given while checking vitamin D levels.
• Reduced mobilization from bone, Osteomalacia

Magnesium

• Renal Magnesium, GI issues, Hormonal changes can result in Renal Magnesium wasting.
• < 2% of total Mg++ in ECF is 20% protein bound, cells include 31%, bone 67%.
• Endocrine
• GI losses, malabsorption, Hyperthyroidism can cause Renal Magnesium wasting
• congenital issues, mutations in DCT can result with DCT issues

Hypomagnesemia

• Cannot decipher serum Mg levels, Gl losses such as malabsorption or laxative abuse

• Hypero can cause renal Mg wasting resulting in hypo , muscle fasiculations, tremors, spasticity, can be caused by the condition resulting sudden , the use of diuretics with drug toxicity with specific meds.

• Treatment , parenteral Mg++ can be administered, diets high in Mg++ can be introduced as a form for treatment.

• Causes include GI losses, endocrine , or renal, resulting in clinical Anorexia, nausea, comiting.

Phosphate

• Extracellular Fluids and Digestive juices help with phosphate uptake, bones work with phosphate.
• Parathyroid Hormone Dietary intakes are sources.
• Cellular model in the parathyroid include lumen, HPO uptake.

Clinical Case

• Symptoms 45male, weight gain abdominal swelling, drinking whisky for 20 years, High BP, liver disease,
• Low Labs: High K+, low HCOL3 and glucose. , high water retention with renal complications from excess drinking.

Volume Status

• Liver and renal related complications from excess alcohol ,
• Renin is increases -Low hypo and renal.Volume.Hyponatremia dilutional, calculate serum as 255Hypontonic. 1.235.9:15 PM Clinical Cases , volume is increased with edema, but renal volume Clinical Cases Describe the Volume status TBW , Renal and Liver relate d complications from alc