[OS 206] E03-T14-Volume and Osmotic Regulation_compressed

Nephron

• The nephron is the functional unit of the kidney
• The glomerulus contains tufts that act as trainers
• Together with the tubules, glomeruli maintain homeostasis and fluid balance
• The tubule regulates urine concentration and dilution, key parts include:
  • Proximal Convoluted Tubules
  • Loop of Henle
  • Distal Convoluted Tubules
  • Collecting duct
• The interstitium holds the glomerulus and tubules together
• The kidneys filter blood, excrete waste into urine, and return the cleaned blood to the body via the renal vein

Hydration Terminology

• Euhydration reflects normal body water content within a homeostatic range of ±2%
• Dehydration involves the dynamic loss of body water
• Rehydration is the dynamic gain of body water through fluid intake
• Hypohydration indicates a state of body water deficit
• Hyperhydration (or overhydration) represents a state of excess body water
• Total Body Water (TBW) combines sodium and water
• Euvolemia is normal body water and sodium content within a homeostatic range
• Hypovolemia is a state of body water and sodium deficit
• Hypervolemia (or overvolemia) signifies excess body water and sodium
• Hydration relates to water, while volemia relates to sodium
• Serum sodium measures both hydration and volume
• If sodium is constant but water increases, sodium lab values decrease, necessitating ion replacement rather than just water, which can cause hyponatremia

Sources of Water Loss

• Hydration status is influenced by various processes that cause body mass loss like:
  • Sweating
  • Urination
  • Insensible water loss (immeasurable water usage)
    • Respiration/breathing
    • Fuel oxidation, water vapor
  • Feces
    • Loss of 100-200 mL water

Body Mass and Water

• Processes increasing body mass involve drinking, eating, and IV fluids
• Urine output, the biggest contributor to water excretion, ranges from 0.5 to 20L daily
• Urine output is dependent on sodium and water intake
  • Water follows sodium

Fluid Compartments

• Total Body Water (TBW) makes up 50-70% of body mass
  • Man: 60%
  • Woman: 50%
  • Babies: 70-75%
• TBW is approximately 0.73 times fat-free mass
• Extracellular Fluid (ECF) is 20% of TBW
• Intracellular Fluid (ICF) is 40% of TBW
• TBW and fluid compartment values should be referenced from Dr. Anacleto’s lecture
• Given a 70kg man, ECF is about 14L
• In a 70 kg man:
  • ECF: 20% of TBW or 14 L
    • Plasma: 5% of TBW or 3L
    • Interstitial Fluid: 15% of TBW or 11 L
  • ICF: 40% of TBW or 28 L
• Fluid moves between compartments based on solute concentration if there is a semipermeable membrane
• Water (intake) goes to the plasma, then moves through the capillary membrane to the interstitial fluid, eventually reaching the intracellular fluid
  • Plasma ↔ Capillary membrane ↔ Interstitial fluid ↔ Cell membrane ↔ Intercellular fluid

Ion Concentration

• Sodium (Na+) is highest in ECF
  • ECF ≅ 140 mEq/L
  • ICF ≅ 4 mEq/L
• Potassium (K+) is highest in ICF
  • ECF ≅ 4 mEq/L
  • ICF ≅ 140 mEq/L
• Magnesium (Mg2+) and Calcium (Ca2+) are predominantly ICF
• Chloride (Cl-) and Bicarbonate (HCO3-) are higher in ECF
• PO4 and organic anions and Protein (e.g., albumin) are higher in ICF
• The Donnan Effect is a phenomenon where:
  • Plasma has a slightly higher concentration of positively charged ions (cations) with a difference of ~2%
  • Plasma proteins, which have a net negative charge, bind to cations (like Na+ and K+), retaining them in the plasma

Osmolarity and Osmolality

• Sodium (Na+) controls water movement between fluid compartments
• Water follows solute to maintain osmotic equilibrium
• Osmolality is osmoles per kilogram of water
• Osmolarity is osmoles per liter of water
• Osmolarity and osmolality are interchangeable because water density is 1 kg/L
• In nephrology, osmolarity is used
• Osmoles include sodium, proteins, and carbohydrates
• Normal Osmolarity in Humans should average 282 mOsm/L, or approximately 2x sodium
• Sodium averages approximately 141 meq/L
• Hyperosmotic solutions have higher osmolarity than normal ECF
• Water shifts out of cells and into the ECF if a hyperosmolar solution is added to the extracellular compartment

Tonicity

• Tonicity is the capability of a solution to modify cell volume by altering water content
• Solution tonicity depends on the concentration of impermeant solutes
• In an isotonic solution:
  • Water concentration is equal inside and outside the cell, and solutes cannot move in or out
  • Cells do not shrink or swell
• In a hypotonic solution:
  • Solute concentration is lower
  • Water diffuses into the cell, causing it to swell
  • Water continues to enter, diluting the ICF and concentrating the ECF until osmolarity is equal
• In a hypertonic solution:
  • Solute concentration is higher
  • Water flows out of the cell into the ECF, concentrating the ICF and diluting the ECF
  • Cells shrink until concentrations are equal
• Osmolarity is the amount of osmoles without cells, and tonicity refers to the action of the cell

Filtration

• Filtration is the net movement of water across a membrane governed by the formula:
  • Filtration = Kf × (PC – PIF –πC + πIF)
• Kf = Capillary filtration coefficient
• PC = Capillary hydrostatic pressure
• PIF = Interstitial fluid hydrostatic pressure
• πC = Capillary osmotic pressure
• πIF = Interstitial fluid osmotic pressure
• Capillary filtration involves fluid and colloid osmotic pressure, which moves fluid through membrane pores
• At the arterial end of the capillary, hydrostatic pressure is high, pushing water and solutes into the interstitial fluid (filtration)
• Filtered water and solutes are absorbed into the lymphatic system, decreasing capillary hydrostatic pressure
• At the venous end, increased plasma protein concentration causes higher oncotic pressure
• Increased oncotic pressure draws water back into the capillary from the interstitial fluid, preventing edema
• Edema accompanies excessive interstitial fluid (e.g., barrier problems, lymphatic obstructions, high hydrostatic pressure, weak Kf)

Clinical Correlates: Hypernatremia and Hyponatremia

• Plasma sodium indicates plasma osmolarity
• Other osmoles
  • Glucose: 5%
  • Amino acids
• Normal value is 140 meq/L
• Sodium stimulates thirst, helps maintain balance among fluid compartments, supports cardiovascular function, and promotes body rehydration
• Hyponatremia: Excess water and loss of sodium
• Hypernatremia: Lack of water and high sodium

Abnormalities of Body Fluid Volume Regulation

• Hyponatremia
  • Dehydration: decreased plasma Na+, decreased ECF volume, increased ICF volume
  • Overhydration: decreased plasma Na+, increased ECF volume and ICF volume
• Hypernatremia:
  • Dehydration: increased plasma Na+, decreased ECF volume, decreased ICF volume
  • Overhydration: increased plasma Na+, increased ECF volume, and decreased ICF volume

Clinical Cases of Hyponatremia

• Gastrointestinal losses due to vomiting and diarrhea result in loss of K+, Cl, Na+, and water
• Loop diuretics (e.g., Furosemide) inhibit Na+ reabsorption in the Loop of Henle, leading to significant Na+ and water loss
• Thiazide diuretics (e.g., Metolazone) act on the distal tubule, blocking Na+ reabsorption
• K+-sparing diuretics (e.g., Spironolactone) act on the collecting duct, reducing Na+ reabsorption while conserving K+
• Diuretics cause reduced Na+ reabsorption by targeting different parts of the nephron

Dehydration and Overhydration

• Dehydration cases
  • Adrenal insufficiency
    • the adrenal gland doesn't make enough adrenal hormones including aldosterone causing decreased sodium reabsorption(2028 Trans)
  • Diabetes insipidus causes too much urine production due to low ADH or kidney unresponsiveness to ADH
  • Excessive sweating
  • Overuse of diuretics
    • Inhibits the ability of the kidneys to conserve sodium and certain types of sodium-wasting kidney diseases (2028 Trans)
• Overhydration cases
  • Excess ADH (SIADH) results in water conservation, diluting blood sodium
  • Bronchogenic tumors
  • Cushing disease with mineralocorticoid activity from cortisol
  • Primary aldosteronism

Effects on the Brain and Sodium Levels

• Normonatremia: Balanced levels of Na+, K+, organic solutes, and H₂O maintaining normal brain cell volume
• Acute Hyponatremia can result from rapid sodium loss or excess water intake
• Rapidly decreasing blood sodium concentration leads to water influx into brain cells, causing cerebral edema

Acute vs Chronic Hyponatremia

• Cellular Mechanism:
  1. Water influx to balance pressure
  2. Export solutes to compensate
  3. Water efflux decreasing swelling
• Chronic Hyponatremia has adaptations such as:
  • A slow prolonged sodium loss
  • The brain gradually expels solutes to minimize swelling
  • Reducing symptoms, but making rapid correction dangerous

Syndrome of Inappropriate ADH (SIADH)

• Inappropriate ADH secretion leads to increased water levels
• Aquaporin 2 water channels on the collecting duct are essential
• Sodium falls below 140 mEq/L

Edema

• Excess fluid in body compartments
  • Extracellular edema: leakage from plasma to interstitial space or failure of lymphatics
  • Intracellular edema: hyponatremia, metabolic system depression, or malnutrition
• Edema components related to filtration equation include capillary filtration coefficient, capillary hydrostatic pressure, and plasma colloid oncotic pressure
• RAAS activation and aldosterone cause edema

Heart Failure

• Heart Failure impairs pumping, elevates venous and capillary pressures, and increases capillary filtration, causing edema
• Changes kidneys
• Reduced blood flow to kidneys stimulates renin secretion and ADH secretion
• Left-Side Heart Failure causes elevated pulmonary vascular pressures and may progress rapidly, even causing death within hours

Conditions that cause Edema

• Common causes -Immobilization, venous problems etc
• Myocardial Fibrosis case -Arterial problems with eventual water retention in the kidneys from body feeling lack of water

Decreased Plasma Proteins

• Failure to produce normal protien ammount
• Decreases plasma osmodic
• Common Causes -Failure to produce from liver damage -Loss from skin or urine

Nephrotic syndrome case

• Albumen spills to urine from kidney problems leading to low serum albumen causing the fluid to build up outside the pulls

Disruption of body water balance

-Hypohydration - body water deficit

• Hypovolemia - decreased plasma volume
• Hyperosmolality - increased plasma osmolality
• Can result in High strain, high body, fatigue

Hydration Assessment

• Measure first thing in the morning before breakfast
• Check weight, urine color, thirsty

Sweating

• Factors impacting the variability in Sweating rate include:Exercise intensity, body , environmental ,Fitness etc

Cardio-Renal Syndrome

• Abnormality in the heart kidney try to draw more fluid -Involved in the words valvular heart disease valve failure lead to regurgitate blood flood over the lungs

Changes by disease

• In urinalysis Protein ranges from negative
• If patient a +4 expect a Lot album

Minimumal diseases of the bodies

• Outer layer membrane layer are are destroyed and effects Kf. Frothy protein

Renal and Liver case

• Patient is overhydrated-Abnormality in the heart will affect the kidney
• Rheumatic heart disease valvular disease lead is more fluid excreted

Diabetes

-Failed antidiuretic hormone (ADH)-Increase urine production -Central if involves the kidneys and outcome has Urine output as high as 15 liters per day

• Water cannot be reabsorbed causes more albumen creation