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Lecturer: Dr. R. Ahangari
Institution: University of Central Florida, Orlando
References: Human Physiology by S.I. Fox and Human Anatomy by Marieb & Mallat

In most individuals, approximately 67% of total body weight is water, distributed as:
- Intracellular Compartment: 67% of total body water
- Extracellular Compartment: 33% of total body water
- Contains about 20% in the cardiovascular system (blood plasma)
- Remaining 80% in the form of tissue fluid, also called interstitial fluid

The extracellular environment consists of:
- Interstitial Fluid: Nutrient and regulatory molecule transport medium
- Matrix Components: Relative to glycoproteins and proteoglycans, supports by:
- Collagen (provides tensile strength)
- Elastin (provides elasticity)
Integrins: Glycoproteins that extend from cytoskeleton through plasma membrane into extracellular matrix, aiding cell adhesion.

Mechanisms for transport across the cell membrane divided into:
1. Carrier-Mediated Transport
- Further subcategorized into:
  a. Facilitated Diffusion
  b. Active Transport
1. Non-Carrier Mediated Transport
- Involves simple diffusion of ions, lipid-soluble molecules, and water.
Osmosis: Defined as the net diffusion of solvent (water) through a membrane.

Passive Transport:
- Movement from higher to lower concentration (downhill) without metabolic energy. Includes:
- Simple diffusion
- Osmosis
- Facilitated diffusion
Active Transport:
- Movement against a concentration gradient (uphill) requiring metabolic energy (ATP) and involves specific carrier proteins.

Characteristics:
- Only form that is not carrier-mediated
- Occurs down an electrochemical gradient (downhill)
- Does not require metabolic energy (passive)
Flux Equation: $J = -PA (C<em>1 - C</em>2)$ Where:
- J = flux (flow in mmol/sec)
- P = permeability (cm/sec)
- A = area (cm²)
- C1 = concentration1 (mmol/L)
- C2 = concentration2 (mmol/L)
Permeability (P):
- Describes solute diffusion ease through a membrane
- Dependent on solute and membrane characteristics.
Factors that increase permeability:
- High oil/water partition coefficient of a solute increases solubility in membrane lipid
- Decrease in solute size increases speed of diffusion
- Decrease in membrane thickness decreases diffusion distance.
Solute Types:
- Small hydrophobic solutes have highest permeabilities
- Hydrophilic solutes cross via water-filled channels or pores.

Characteristics:
- Applies to facilitated diffusion, primary and secondary active transport.
- Stereospecificity: Example: D-glucose vs. L-glucose, where only D-glucose is transported.
- Saturation: Transport rate increases till carriers are saturated (analogous to V max in enzyme kinetics)
- Competition: Similar solutes may compete for transport sites; e.g., galactose inhibits glucose transport.

Characteristics:
- Occurs downhill (passive, carrier-mediated)
- More rapid than simple diffusion
- Exhibits stereospecificity, saturation, and competition.
Example:
- Glucose transport in muscle/adipose cells; facilitated diffusion inhibited by galactose. Insulin required for glucose uptake in diabetes mellitus.

Characteristics:
- Occurs uphill (against gradient)
- Requires ATP (active)
- Carrier-mediated, with stereospecificity, saturation, and competition.
Examples:
- Na+/K+ Pump: Transports Na+ out and K+ into cells (3 Na+/2 K+ stoichiometry).
  - Specific inhibitors include ouabain and digitals.
- Ca2+ ATPase: Calcium transport against gradient in SR/cell membrane.
- H+/K+ ATPase: Proton transport in gastric parietal cells against gradient; inhibited by omeprazole.

Osmolarity:
- Concentration of osmotically active particles in solution, measured via:
  - Freezing point depression.
- Osmolarity Equation:
  $\text{Osmolarity} = g \times c$
  Where:
- g = number of particles in solution (osm/mol)
- c = concentration (mol/L)
Isosmotic Solutions:
- Same osmolarity; hyperosmotic (higher) vs. hyposmotic (lower).
Osmosis Flow:
- Water moves from low to high solute concentration across semipermeable membrane.
Osmotic Pressure Calculation (van’t Hoff’s Law): $OP = g \times C \times RT$ Where:
- OP = osmotic pressure (mmHg or atm)
- R = gas constant (0.082 L-atm/mol)
- T = absolute temperature (K)
Increased osmotic pressure correlates with increased solute concentration.

Defined as:
- A number (0 to 1) measuring ease of solute membrane permeability.
- RC = 1: Solute is impermeable. E.g., Serum albumin (osmotic pressure generator).
- RC = 0: Solute is permeable without osmotic effect. E.g., Urea (ineffective osmole).
Effective osmotic pressure = Osmotic Pressure x Reflection Coefficient.

CF results from genetic defect affecting NaCl and water transport across epithelial membranes, causing thick mucus in pancreatic ductules and respiratory airways.
CFTR Protein: Affected due to improper processing in the Golgi, linked to CFTR gene mutation affecting chloride channels in epithelial cells.

CFTR gene mutation results in dysfunctional chloride transport, entrapping chloride outside host cells, yielding pathological conditions.

Increased blood osmolality triggers:
1. Stimulation of hypothalamic osmoreceptors
2. Increased thirst response; drinking water
3. Decreased urine volume; increased concentration
Normal plasma osmolality: 280 - 303 milli-osmoles/kg.

Fluid return from tissue to blood is osmotically driven by plasma protein concentration.
Low plasma protein levels lead to tissue fluid accumulation (edema), observed in conditions like liver cirrhosis, which diminishes albumin production.