Physiology for Engineers

1. Michael Chappell & Stephen Payne Physiology for Engineers www.physiologyforengineers.org

2. Overview • We are interested in: • Structure - how it is built. • Function - how it works. • Not a classic course in physiology. • We want to be quantitative: • Describe with mathematical models. • Take measurements. • We ultimately want to see what physiological questions we can answer with your core engineering knowledge.

3. Overview • Chapters 1-4: Cellular Physiology • Cell structure and biochemical reactions • Cellular homeostasis and membrane potential • The action potential • Cellular transport and communication • Chapters 5-10: Systems Physiology • Pharmacokinetics • Tissue Mechanics • Cardiovascular system I: The heart • Cardiovascular system II: The vasculature • The respiratory system • The central nervous system

4. Chapter 1 Cell structure and biochemical reactions

5. Introduction Objective: To introduce the ‘cell’ and start to assemble the maths needed to describe what is going on inside • The cell • Structure • Contents • Function • Biochemical Reactions • Units • Mass action kinetics • Enzymes

6. Cell Structure • The cell is classified as the smallest, independently viable morphological unit of a living organism, that is equipped with all functions of life • Self-contained • Self-maintaining • Four main parts: • Cell membrane (outer shell). • Nucleus (control centre / DNA). • Organelles (small internal structures). • Cytoplasm (liquid filling rest of cell). Figure taken, without changes, from OpenStax College under license: http://creativecommons.org/licenses/by/3.0/

7. Cell Functions • Huge variety of cells • brain (astrocytes, glia...), heart, liver, blood ... • All cells have several common abilities: • Reproduction by cell division (binary fission/mitosis or meiosis). • Metabolism, including taking in raw materials, building cell components, converting energy, molecules and releasing by-products • Use of enzymes and other proteins coded for by DNA genes and made via messenger RNA intermediates and ribosomes. • Response to external and internal stimuli (temperature, pH, nutrients)

8. Cell Contents • Cells are composed of a restricted set of elements • Carbon (C), Hydrogen (H), Nitrogen (N) and Oxygen (O): 99% of cell weight • Most abundant substance is water, H2O: 70% Inorganic Organic

9. Cell Contents • Small molecules act as intermediates for the synthesis of larger molecules. • Sugars —> Saccharides (di, oligo, poly) • Fatty acids —> Lipids (e.g. phospholipids) • Nucleotides —> DNA, RNA • Amino acids —> Peptides, Proteins Organic

10. Proteins • Proteins are built from small subunits: amino acids • ~20 common amino acids Primary Structure Secondary Structure Polypeptide Protein Figure taken, without changes, from OpenStax College under license: http://creativecommons.org/licenses/by/3.0/

11. Proteins • Proteins have a range of roles: • Structural, e.g. support. • Regulatory, e.g. hormones, insulin, control of metabolism. • Contractile, e.g. myosin in muscles. • Immunological, e.g. antibodies, immune system. • Transport, e.g. movement of materials, haemoglobin for oxygen. • Catalytic, e.g. enzymes.

12. ATP • Energy source for cells. • Energy is released by removing phosphate groups adenosine Phosphate chain Ribose ATP ADP AMP Energy Energy

13. Contents • The cell • Structure • Contents • Function • Biochemical Reactions • Units • Mass action kinetics • Enzymes

14. Units • Basic unit for substance is the mole. • Formally defined as number of atoms found in 12 grams of 12C (6.022 x 1023 atoms). • Most substances in the body are found in solution (normally water). • Concept of molarity. • Defined as number of moles of the solute per litre of the solution. • Units are mol/l, normally written as M (mM = milli-mol).

15. Mass action kinetics • A simple reaction: • k is the rate constant for this reaction, which simply converts A and B (the reactants) to C (the product). • ‘Law’ of mass action states: • More generally: [A] is the concentration of A

16. Mass action kinetics • Elementary reactions • In essence a collision between the elements A and B. • Rate depends on: • Collision rate. • Activation Energy - hence temperature. • Shape of A and B. • This model is not very good if either [A] or [B] is very low.

17. Mass action kinetics • ‘Law’ of mass action is actually a model. • Only applies when concentrations are not very high or low. • Is appropriate for elementary reactions • Many reactions occur in multiple steps • Mass action might still be a good first approximation. • Many reactions have a ‘rate-limiting’ step.

18. Mass action kinetics • All reactions proceed both forward and backward: • Can write rate equations for each substance:

19. Mass action kinetics

20. Mass action kinetics • More generally: • We can define the equilibrium constant: • Indicates how far the reaction proceeds toward either side in equilibrium.

21. Enzymes • Enzymes are biological catalysts: • Unchanged by the reaction. • Help the reaction to occur by making it more favourable: • Increase probability of collision by brining species together. • Reduce activation energy, e.g., make bonds easier to break. • Very common in cellular reactions. Figure taken, without changes, from OpenStax College under license: http://creativecommons.org/licenses/by/3.0/

22. Enzymes • ‘Enzyme’ example - bringing species together • The enzyme has locations where the species can ‘dock’ next to each other. Figure taken, without changes, from OpenStax College under license: http://creativecommons.org/licenses/by/3.0/

23. Enzyme kinetics • Michaelis-Menten model: • Enzyme converts substrate into complex • Complex breaks down into products • Assumptions: • Second reaction is uni-directional • S is in equilibrium with complex (ES) - equilibrium approximation. • OR rate formation and breakdown of complex are equal - Quasi steady state approx.

24. Enzyme kinetics • Michaelis-Menten equation • V is the reaction ‘velocity’ • Vmax = k2[E]0 - related to amount of available enzyme. • linear at low concentration • saturates at high concentration

25. Enzyme co-operativity • Enzymes might bind more than one substrate molecule. • Binding of first might affect binding of further substrate. • Hill equation: • n = number of substrates bound by single enzyme molecule • in practice n is determined by best fit to data.

26. Enzyme co-operativity • Example: Oxygen transport • Haemoglobin in the blood binds oxygen to increase the amount carried: • Expect n = 4 • In practice n = 2.5 is better fit • Hill equation is also a good general purpose model for more complex reactions, e.g. multi-step reactions

27. Enzyme inhibition • Competitive - inhibitor binds to same site as the substrate, making it harder for the product to form. Mainly affects the linear behaviour - when [S] is small

28. Enzyme inhibition • Allosteric - inhibitor binds to another site on the enzyme affecting the binding of the substrate. • Allosteric inhibitor that does not compete with S (uncompetitive). Mainly affects the saturation behaviour - when [S] is large In this model I binds to ES preventing formation of P

29. Enzyme inhibition • Allosteric (uncompetitive) • Competitive

30. Enzyme inhibition • Inhibitor could be competitive at the same time:

31. Enzyme kinetics • More complex enzyme schemes are possible

32. Michael Chappell & Stephen Payne Physiology for Engineers www.physiologyforengineers.org