Lecture 5

Cells

1. Levels of organization The body is built in levels, each depending on the one below: chemical → cell → tissue → organ → organ system → organism. The lecture's example is the stomach: hydrochloric acid and enzymes (chemical level) are made by the parietal cell (cell), which sits in the gastric epithelium (tissue), which lines the stomach (organ), which belongs to the digestive system (system) that supplies the organism. Every cell carries out the basic functions common to all cells and, in addition, one specialized activity. The body has four primary tissue types:

  • Muscle — contracts to produce force and movement.

  • Nervous — rapid electrical signaling for control and communication.

  • Epithelial — covers surfaces, lines cavities, forms glands.

  • Connective — support, energy storage, connects tissues.

An organ is two or more tissue types working together — the stomach has smooth muscle for mixing, epithelium for secretion, nervous tissue for control and connective tissue for support. An organ system is a group of organs with a common purpose.

2. Homeostasis Homeostasis is the maintenance of a relatively stable internal environment despite changing external conditions. Physiological variables are held within a normal range, not at a single fixed value — temperature, pH, fluid and electrolyte balance, and blood glucose are the classic examples. Most regulation is by negative feedback, in which the response opposes the change: a rise in blood glucose triggers insulin, which lowers it; a fall triggers glucagon, which raises it. Learn the logic well enough to recognize negative feedback in any system you meet later in the course.

3. Body fluid compartments and their composition Total body water is divided into intracellular fluid (ICF), about two-thirds of the total and inside the cells, and extracellular fluid (ECF), about one-third. The ECF is further divided into plasma (in the blood vessels) and interstitial fluid (between the cells). The key principle: cells live in the ECF. It is the body's "internal environment," from which cells extract nutrients and into which they deposit wastes, and every organ system ultimately acts to keep that environment constant. The two compartments have opposite ionic compositions. ICF is high in K⁺, low in Na⁺ and high in protein. ECF is high in Na⁺, low in K⁺, and interstitial fluid is low in protein. These differences are maintained by selective barriers: the capillary wall separates plasma from interstitial fluid, and the plasma membrane separates ICF from ECF. The Na⁺/K⁺ gradient you learn here is the basis of the membrane potential in Lecture 5B.

4. The plasma membrane The plasma membrane surrounds every cell and defines the boundary between ICF and ECF. It is a thin, flexible lipid barrier with four jobs: selective transport, communication through receptors, cell adhesion, and maintenance of the ion gradients that make excitability possible. The lipid bilayer does three things: it is the structural foundation, it is a selective barrier (the hydrophobic core blocks water-soluble molecules, keeping ICF and ECF distinct), and it is fluid. The bilayer is fluid rather than rigid — more like cooking oil than solid fat — because phospholipids are not covalently linked; they rotate, vibrate and shift within their own layer millions of times a second. Membrane proteins are embedded in or attached to the bilayer and drift within it like icebergs; this is the fluid-mosaic model. The membrane proteins to know:

  • Water-filled channels and carrier (transport) molecules.

  • Receptors for circulating chemical signals, on the outer surface.

  • Cell adhesion molecules (CAMs), on both surfaces.

  • Docking markers for secretory vesicles, on the inner surface.

  • Enzymes, on both surfaces.

  • Glycoproteins (protein plus carbohydrate), on the outer surface.

5. Cell–cell adhesions Cells are held together into tissues by three mechanisms:

  • Extracellular matrix (ECM) — a scaffold of fibrous proteins in a watery, gel-like ground substance of complex carbohydrates; the interstitial fluid filling it is the route by which nutrients, wastes and water-soluble substances diffuse between blood and cells.

  • Cell adhesion molecules (CAMs) — membrane proteins that link cells to each other and to the ECM.

  • Specialized cell junctions — tight junctions, desmosomes and gap junctions.

The three specialized junctions:

  • Tight junctions seal epithelial sheets: adjacent cells are bound closely at points of contact, closing off the space between them. Abundant in epithelia lining body surfaces and cavities; relatively impermeable, preventing passage of most substances between cells, though slightly "leaky" to water and small ions.

  • Desmosomes act like spot welds that anchor two cells together without fusing them. Dense protein plaques inside each membrane are linked across the gap by cadherins, and intermediate filaments (keratin in epithelia, desmin in cardiac muscle) attach inside each cell for strength. Found in tissues subject to stretching — skin, heart, uterus.

  • Gap junctions are communicating junctions that let ions and small water-soluble molecules (Ca²⁺, cAMP) pass directly between neighboring cells, bypassing the ECF. Each channel is two connexons joined end to end across the 2–4 nm gap, each connexon made of six connexin subunits; the pore is about 1.5 nm, so ions and small molecules pass and large ones do not. Abundant in cardiac and smooth muscle, where ion flow synchronizes electrical activity so a whole muscle mass contracts together (the heartbeat); they also couple the fiber cells of the lens.

6. Selective permeability and simple diffusion To move between a cell and the ECF a substance must cross the plasma membrane. The membrane is permeable to substances that pass directly through the bilayer — O₂, CO₂ and lipid-soluble molecules — and impermeable to those that cannot — ions, glucose and other polar molecules — which need a transport protein or channel. Overall the membrane is selectively permeable. Simple diffusion needs no protein and no energy. When the concentration of a particle in area A exceeds that in area B, a concentration gradient exists; molecules move randomly in all directions, but the net movement is from high to low concentration. Net diffusion is the difference between the two opposing flows, and it stops when the concentrations are equal. Fick's law gathers the factors that set the rate of net diffusion:

  • Directly proportional to the concentration gradient, the surface area available, and the permeability of the membrane to the substance.

  • Inversely proportional to the thickness of the membrane and the molecular weight of the substance.

Use it as a checklist — anything that thickens a membrane (edema) or reduces its area (lung disease) slows diffusion.

7. Osmosis and tonicity Osmosis is the net diffusion of water across a membrane that is permeable to water but not to the solute. Three cases, in terms of nonpenetrating solute:

  • ECF solute concentration lower than ICF → water moves into the cell → cell swells.

  • ECF concentration higher than ICF → water moves out → cell shrinks.

  • Concentrations equal → no net water movement → volume constant.

Osmosis is the primary force moving water into or out of cells.

Tonicity is the clinical vocabulary for the same three cases: it describes a solution by what it does to a cell.

  • Hypotonic — ECF less than ICF; cell swells.

  • Isotonic — equal; no change.

  • Hypertonic — ECF greater; cell shrinks.

Only nonpenetrating solutes count — a solute that can cross the membrane cannot hold water on one side. Clinical note: corneal edema seen at the slit lamp is treated with a hypertonic solution — 5% NaCl drops draw water out of the stroma.

8. Ion diffusion and the electrochemical gradient Uncharged solutes are driven by a concentration gradient alone, and water by the solute it cannot follow. Ions are a third case: they carry charge, so a second force appears. A charge difference across the membrane is an electrical gradient (a voltage), and like charges repel while opposite charges attract. An ion therefore feels two forces — the concentration gradient (high to low) and the electrical gradient (toward the opposite charge) — which together form the electrochemical gradient. Ions cannot cross the lipid bilayer directly; they need a channel or transporter. This is the bridge to Lecture 5B.

9. Carrier-mediated transport: facilitated diffusion and active transport Ions, glucose and amino acids cannot cross the bilayer on their own, so the membrane provides carrier proteins. Carrier-mediated transport comes in two forms. Facilitated diffusion is passive: no cellular energy, movement down the concentration gradient, through carrier proteins such as the GLUT transporters that bring glucose into cells. Active transport requires ATP or an ion gradient and moves substances against their gradient, using pumps or transporters such as the Na⁺/K⁺-ATPase or the proton pump. Because both are carrier-mediated, both are specific, saturable and subject to competition — three properties simple diffusion does not have.

  • Primary active transport uses ATP directly. The Na⁺/K⁺ pump moves 3 Na⁺ out and 2 K⁺ in per ATP; the net export of one positive charge per cycle makes it electrogenic.

  • Secondary active transport uses no ATP directly: it uses the Na⁺ gradient created by the pump to drive another substance, either in the same direction (the Na⁺/glucose cotransporter, a symport) or the opposite direction (the Na⁺/Ca²⁺ exchanger, an antiport).

The two work together — stop the pump and secondary transport runs down as the Na⁺ gradient dissipates.

10. Vesicular transport Large molecules and bulk material cross the membrane by vesicles; the process requires ATP and the cytoskeletal machinery.

  • Endocytosis — uptake of material (LDL cholesterol).

  • Exocytosis — release of material (neurotransmitters, hormones).

11. Clinical connections Five places where membrane transport explains a clinical picture — each is a direct application of a mechanism above, and that is how to study them: pump, osmosis, tight junction, gap junction.

  • Cornea — transparency depends on relative dehydration maintained by the endothelial Na⁺/K⁺- ATPase pumping ions out of the stroma with water following; endothelial loss (Fuchs dystrophy, surgical trauma) causes stromal edema and clouding.

  • Hypertonic saline — 5% NaCl draws water osmotically out of the stroma: tonicity applied at the slit lamp.

  • Aqueous humor — secretion by the ciliary epithelium depends on Na⁺/K⁺-ATPase and carbonic anhydrase, so carbonic anhydrase inhibitors lower intraocular pressure by reducing secretion.

  • Blood–retinal barrier — the outer barrier is tight junctions between retinal pigment epithelial cells; breakdown allows fluid accumulation and macular edema.

  • Lens — fiber cells are coupled by gap junctions (connexins 46 and 50); mutations in these connexins cause inherited cataract.

Must-know table

Body water: ICF ≈ 2/3, ECF ≈ 1/3; ECF = plasma + interstitial fluid; cells live in the ECF

Ionic composition ICF: high K⁺, low Na⁺, high protein. ECF: high Na⁺, low K⁺; interstitial fluid low protein

Four tissue types: Muscle, nervous, epithelial, connective

Negative feedback Response opposes the change (glucose ↑ → insulin → glucose ↓)

Fluid-mosaic model: Fluid bilayer (no covalent links between phospholipids); proteins drift within it

Tight junction: Seals epithelia; blocks paracellular passage; slightly leaky to water and small ions

Desmosome Spot weld; cadherins + intermediate filaments; skin, heart, uterus Gap junction Two connexons (6 connexins each), ≈1.5 nm pore; cardiac & smooth muscle, lens

Passes bilayer freely O₂, CO₂, lipid-soluble molecules

Needs a protein Ions, glucose, amino acids, water in bulk (aquaporins)

Fick's law Rate gradient × area × permeability ÷ thickness

Tonicity Hypotonic → swell; isotonic → no change; hypertonic → shrink; only nonpenetrating solutes count

Electrochemical gradient Concentration gradient + electrical gradient; applies to ions only

Facilitated diffusion Passive, down gradient, carrier (GLUT); specific, saturable, competition Na⁺/K⁺-ATPase 3 Na⁺ out, 2 K⁺ in per ATP; electrogenic; primary active transport

Secondary active Uses Na⁺ gradient, no direct ATP; symport (Na⁺/glucose) or antiport (Na⁺/Ca²⁺)

Vesicular transport Endocytosis (LDL) / exocytosis (transmitters, hormones); needs ATP