Fundamentals of Anaesthesia - Cellular Physiology

Question 1

Define cytoplasm.

Answer 1

‘Cytoplasm’ is used to describe all intracellular contents outside the nucleus. It consists of the organelles and the cytosol.

Question 2

Define cytosol

Answer 2

Cytosol refers to the intracelluar fluid containing proteins and electrolytes.

Question 3

What is the role of the cytoskeleton?
What are its main components (from largest to smallest)?
Which mechanisms underlies cellular motion and shape changes?

Answer 3

This system of microscopic fibres maintains the cell structure and enables cell movement to occur. Its main components are:

Microtubules – 25 nm diameter structures with 5 nm thick walls.
Muscle thick filaments – composed of myosin 15 nm in diameter
Intermediate filaments – solid fibres about 10 nm in diameter
Microfilaments – solid fibres about 5 nm in diameter made of polymerised actin

Cellular motion, shape changes and ciliary or flagellar movement all involve molecularmotor mechanisms based on the action of ATPases.

Question 4

What is the main role of mitochondia?
Describe their inner membrane.
What does the matrix contain?

Answer 4

Their main function is to produce chemical energy in the form of ATP by oxidative phosphorylation.
The inner membrane is folded to form cristae, which are studded with units containing the oxidative phosphorylating and ATP-synthesising enzymes.

The matrix contains enzymes required to drive the citric acid cycle, which in turn provides the substrate for oxidative phosphorylation.

Question 5

What are the roles of the rough and smooth endoplasmic reticula?

Answer 5

This membranous structure is composed of complex folds and tubules. In its granular form, ribosomes are attached to the cytoplasmic surfaces and are the primary site for protein synthesis in the cell. Agranular ER is free from ribosomes and is the site of steroid synthesis and detoxification.

Question 6

Composition of ribosomes? What is their role?

Answer 6

Ribosomes are about 32 nm in diameter with large and small subunits. They are composed of 65% RNA and 35% protein, and are the sites of protein synthesis.

Question 7

What is the structure of the Golgi apparatus? What is its role?

Answer 7

This consists of flattened membranous sacs or cisterns that are stacked together to form a polarised structure with cis and trans ends, separated by a middle region. The Golgi apparatus prepares proteins for secretion (via exocytosis) by receiving the proteins from the ER at the cis side, coding them for destination and finally producing secretory granules or vesicles at the trans side.

Question 8

What are the three basic types of cellular junction?

Answer 8

Desmosomes – disc-shaped junctions that provide
mechanical bonding between cells subject to stress
(e.g. epithelium, skin)

Tight junctions – circumferential junctions that seal
the extracellular space between epithelial cells,
preventing the passage of molecules between cells

Gap junctions – small channels (diameter 1.5 nm) that
allow transfer of small ions and molecules between
cells

Question 9

What are the main families of cell adhesion molecules and their properties (4)?

Answer 9

Integrins - Platelet adhesion, expressed on leujocytes and binds to IgSF, leukocyte motility, cell-matrix adhesion

Selectins - Expressed on circulating leukoytes, stored in endothelial cells and allow rolling of leukocytes, stored in platelets.

Cadherins - morphogenesis of tissues, metasis of tumours, embryological development

Immunoglobulin superfamily (IgSF) - endothelium (bind to integrins), gut mucosa (bind to selectins)

Question 10

Structure of G-proteins?
How are they activated?
What does activation enable?
How are they deactivated?

How does G(αs) function? Examples(6)
How does G(αi) function? Examples (2)
How does G(αq/11) function? (

Answer 10

Heterotrimeric G proteins, sometimes referred to as the “large” G proteins, are activated by G protein-coupled receptors and are made up of alpha (α), beta (β), and gamma (γ) subunits.

They are activated in response to a conformational change in the G-protein coupled receptor (due to ligand binding), exchanging GDP for GTP, and dissociating in order to activate other proteins in a particular signal transduction pathway.

The activated G protein then deactivates itself by intrinsic GTPase activity. This reduces the GTP to GDP, thus deactivating the G protein.

G(αs) -activates adenylate cyclase, creating cAMP, activating PKA. E.g. - ADH, adrenaline, ADH, Glucagon, FSH/LH, TSH.

Gαi inhibits the production of cAMP from ATP. e.g. somatostatin, prostaglandins.

Gαq/11 stimulates the membrane-bound phospholipase C beta, which then cleaves PIP2 (a minor membrane phosphoinositol) into two second messengers, IP3 and diacylglycerol (DAG). ADH, TSH, Angiotensin II

Question 11

What is diffusion?

Which equation describes rate of diffusion (Q)?

Answer 11

Diffusion describes the resultant movement of solute molecules due to their random thermal motion. It is a passive process, and net movement of the solute occurs when a concentration gradient is present (from a high to a low concentration).

Q = kp x A(C1 − C2)/D
The permeability constant, kp, depends on the local temperature and the characteristics of the membrane; molecular properties also affect it.

Question 12

The phospholipid bilayer is relatively permeable to (2)? And relatively impermeable to (2)?

Which factors increase (4) and decrease (3) rate of diffusion across a cell membrane?

Answer 12

The phospholipid bilayers are relatively impermeable to ions and large polar (hydrophilic) molecules, but permeable to small polar molecules and lipophilic substances.

Increases with concentration gradient
Increases with surface area
Increases with temperature
Increases with lipid solubility
Decreases with membrane thickness
Decreases with molecular weight
Decreases with electrical charge of particle

Question 13

What is osmosis?
What is the molar concentration of pure water?
How does addition of solute affect the concentration of water?
What is the concentration of water in a 1M NaCl solution?

Answer 13

This term describes the net movement of water molecules due to diffusion between areas of different concentration.

Pure water has a molar concentration of 55.5M. In a solution, the addition of solute reduces the water concentration by replacing some water molecules with a solute molecule (or ion).

Each molecule of NaCl produces two particles, a sodium ion and a chloride ion. The 1M solution of NaCl then has a water concentration of 55.5 – 2 = 53.5 M.

Question 14

What is osmolarity? How would the osmolarity of a 1M glucose solution and 1M NaCl solution differ?

Answer 14

The concentration of a solution can be expressed in terms of its osmolarity, reflecting the osmotic effect of the solute particles. The osmolarity of the 1 M glucose solution is thus 1 Osm (osmol l−1) while the 1 M NaCl solution has an osmolarity of 2 Osm.

Question 15

What is osmotic pressure?

Answer 15

A concentration gradient of water can be produced between two compartments separated by a semipermeable membrane. Water diffuses across from the compartment with high concentration of water to that with low concentration (low to high concentration of solute) increasing the volume/pressure of that compartment. The pressure required to resist that movement of water is osmotic pressure.

Question 16

What are hypo- and hyper-tonic solutions? How do they affect cells?

What is the osmolarity of normal ECF? How does it compare to that of intracellular fluid?

Answer 16

Net movement of water into the cell occurs when the cell is placed in a solution of lower osmolarity (hypotonic), giving rise to swelling and ultimately cell disruption or haemolysis. Placing a cell in a solution of higher osmolarity than the intracellular contents (hypertonic) causes shrinking.

Normal extracellular fluid has an osmolarity of 300 mOsm, which is equal to (isotonic) that of the intracellular fluid.

Question 17

How do tonicity and osmolarity differ?

How does normal saline compare with 5% glucose solution?

Answer 17

Osmolarity is expressed in units of solute/volume. It can be measured on a machine called an osmometer, and it has units, usually osmoles or milliosmoles per litre.

Tonicity is a behavioral term. It describes what a
solution would do to a cell’s volume at equilibrium if the cell was placed in the solution.

Tonicity depends on osmolarity and whether the solute can enter the cell (i.e. are they penetrating?).

Both are isoosmotic but NaCl is isotonic (as ions do not easily cross the cell membrane) whilst glucose is hypotonic.

Question 18

What is active transport?

What is the difference between uniport, symport and antiport?

Answer 18

Active transport is mediated by integral membrane proteins or carriers that bind a substance on one side of the membrane, undergo a conformational change and then release the substance on the opposite side of the membrane.

Carriers may be specific for a given substance (uniport), or they may transport a combination of substances (symport), or finally, they may exchange one substance for another (antiport).

Question 19

Why does active transport require energy expenditure?

How does primary active transport work? Where is the energy obtained from?

How does secondary active transport work? Where is the energy obtained?

Answer 19

Active transport equires energy as usually moves against concentration/electrochemical gradient.

In primary active transport, energy is obtained directly from the hydrolysis of ATPand then catalysed by the carrier, which binds the released phosphate. Phosphorylation of the carrier produces covalent modulation of its structure. Na+K+ATPase is an antiport carrier responsible for maintaining transmembrane ion gradients of Na+ and K+.

In secondary active transport, a symport carrier transports a substance and an ion (usually sodium), with binding of the ion causing the conformational change. Energy is derived from the energy put in to maintaining the concentration gradient.

Question 20

What is facilitated diffusion?

Answer 20

Facilitated diffusion describes the transport of a substance from a high to low concentration via a carrier. No energy coupling is required for this process, since movement occurs down the concentration gradient. However, diffusion is not involved, and thus the transport kinetics are characteristic of carrier-mediated transport and carrier saturation occurs.

Question 21

How do exo/endocytosis work?

Answer 21

This mode of transport does not require substances to
pass through the membrane structure, but transports substances contained in membrane-covered vesicles. In endocytosis, extracellular material is absorbed by being packaged into vesicles at the cell membrane. The vesicles are formed by invagination of the membrane. An equivalent process in reverse is exocytosis, which allows the cell to export intracellular substances or debris.

Question 22

What are the three types of RNA?

Which is the most abundant?

Answer 22

Three types of RNA are recognised: messenger (mRNA), transfer (tRNA) and ribosomal (rRNA). They are all synthesised in the nucleus using DNA as a template, but differ from each other in molecular size and function. The bulk of cellular RNA is rRNA, which together with specific proteins forms the ribosomal subunits; however, its function remains uncertain.