HumanBiology

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This section covers the structural and functional organisation of the body, the structure and function of cells and tissues, the biomolecules, cell growth, division and death, transport across membranes, cell signalling, and the basics of immunology.

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Levels of Organisation The body is organised in ascending levels: chemical (atoms and molecules) → organelle → cell → tissue → organ → organ system → organism.

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The cell is the basic structural and functional unit of life, and the whole design serves homeostasis — the maintenance of a relatively constant internal environment despite external change. • Homeostasis is maintained by negative feedback, in which a receptor detects a deviation, a control centre (usually the hypothalamus or brain stem) compares it with a set point, and an effector reverses the change: body temperature, blood glucose, blood pressure, pH and osmolarity are all regulated this way.

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Positive feedback amplifies a change and is rare — childbirth (oxytocin), blood clotting and the upstroke of the action potential. • Control and regulation of body function is shared by the nervous system (fast, electrical, short-lived, precisely targeted) and the endocrine system (slower, chemical via hormones in the blood, longer-lasting, widespread). • The eleven organ systems: integumentary, skeletal, muscular, nervous, endocrine, cardiovascular, lymphatic/immune, respiratory, digestive, urinary and reproductive. • Body fluid compartments: total body water is about 60 % of body weight, divided into intracellular fluid (~2/3, 40 % of body weight) and extracellular fluid (~1/3, 20 %), the latter being interstitial fluid (~15 %) plus plasma (~5 %).

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The Cell and its Organelles Organelle Function Plasma membrane Fluid-mosaic lipid bilayer with proteins; selective permeability, transport, receptors, cell recognition Nucleus Contains DNA as chromatin; site of replication and transcription; nucleolus makes ribosomal RNA Mitochondrion Powerhouse — oxidative phosphorylation producing ATP; has its own circular DNA, maternally inherited Rough ER Studded with ribosomes; synthesis and folding of proteins for export and membranes Smooth ER Lipid and steroid synthesis, detoxification, calcium storage (sarcoplasmic reticulum in muscle) Golgi apparatus Modifies, sorts and packages proteins into vesicles Lysosome Acid hydrolases for intracellular digestion — the 'suicide bag' Peroxisome Oxidation of fatty acids; breaks down hydrogen peroxide by catalase Ribosome Site of translation (protein synthesis); free or bound to ER Cytoskeleton Microfilaments (actin), intermediate filaments, microtubules (tubulin) — shape, movement, transport, mitotic spindle Tissues Tissue type Features and examples Epithelial Covers surfaces and lines cavities; avascular, rests on a basement membrane; simple/stratified, squamous/cuboidal/columnar; functions: protection, absorption, secretion, filtration Connective Cells sparse in an abundant extracellular matrix of fibres (collagen, elastin, reticular) and ground substance; includes loose and dense connective tissue, adipose, cartilage, bone and blood Muscle Skeletal (striated, voluntary, multinucleate), cardiac (striated, involuntary, branched, intercalated discs, functional syncytium) and smooth (non-striated, involuntary) Nervous Neurons (excitable, conduct impulses) and neuroglia (support, insulation, immune defence) Biomolecules Class Building block and key points Carbohydrates Monosaccharides (glucose, fructose) → disaccharides (sucrose, lactose) → polysaccharides (glycogen = animal storage, starch, cellulose).

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Chief immediate energy source, 4 kcal/g; glycocalyx for cell recognition Lipids Fatty acids and glycerol; triglycerides (storage, 9 kcal/g), phospholipids (amphipathic — the basis of every membrane), steroids (cholesterol, membrane fluidity and precursor of steroid hormones), eicosanoids Proteins 20 amino acids joined by peptide bonds; primary → secondary (α-helix, β-sheet) → tertiary → quaternary structure; functions: enzymes, structure, transport, hormones, antibodies, contraction;

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4 kcal/g; denaturation by heat or pH destroys function Nucleic acids Nucleotides = pentose sugar + phosphate + nitrogenous base.

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DNA: deoxyribose, double helix, bases A-T and G-C, stores information.

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RNA: ribose, single strand, U replaces T; mRNA, tRNA, rRNA.

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ATP is the energy currency Cell Growth, Division, Apoptosis and Oncogenic Transformation • Cell cycle: interphase (G₁ → S → G₂) followed by M phase.

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DNA is replicated in S phase.

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Cells that leave the cycle enter G₀.

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Progress is driven by cyclins and cyclin-dependent kinases and policed at checkpoints (G₁/S, G₂/M and the spindle checkpoint), with p53 the best-known guardian. • Mitosis (prophase, metaphase, anaphase, telophase + cytokinesis) gives two genetically identical diploid (2n) daughter cells and serves growth and repair.

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Meiosis occurs only in the gonads, involves two divisions with crossing over, and gives four genetically distinct haploid (n) gametes. • Apoptosis is programmed cell death — an orderly, energy-requiring, genetically controlled process in which the cell shrinks, the chromatin condenses, the DNA is cleaved into a characteristic ladder, and apoptotic bodies are phagocytosed without inflammation.

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It is executed by caspases via an intrinsic (mitochondrial, cytochrome c, Bcl-2/Bax) and an extrinsic (death-receptor, Fas/TNF) pathway.

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Necrosis, by contrast, is uncontrolled death from injury, with swelling, membrane rupture and inflammation. • Oncogenic transformation: cancer arises from the accumulation of mutations that activate proto-oncogenes into oncogenes (gain of function — RAS, MYC, HER2), inactivate tumour suppressor genes (loss of function — p53, RB, BRCA) and impair DNA repair.

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The hallmarks of cancer include sustained proliferative signalling, evasion of growth suppressors, resistance to apoptosis, replicative immortality (telomerase), angiogenesis, and invasion and metastasis.

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Carcinogens may be chemical, physical (ionising radiation, UV) or biological (HPV, hepatitis B, H. pylori).

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Cell-to-Cell Transport Mechanisms Mechanism Description Simple diffusion Passive movement down the concentration gradient; no carrier, no energy — O₂, CO₂, lipid-soluble molecules Facilitated diffusion Down the gradient through a channel or carrier protein; no ATP but saturable and specific — glucose via GLUT Osmosis Diffusion of water across a semipermeable membrane down its water potential, often via aquaporins Primary active transport Against the gradient using ATP directly — the Na⁺/K⁺-ATPase pumps 3 Na⁺ out for 2 K⁺ in, which is electrogenic and maintains the resting potential; also Ca²⁺-ATPase and H⁺/K⁺-ATPase Secondary active transport Uses the gradient established by a primary pump — symport (Na⁺-glucose, SGLT) or antiport (Na⁺/Ca²⁺ exchange) Endocytosis / exocytosis Bulk transport in vesicles — phagocytosis (solids), pinocytosis (fluid), receptor-mediated endocytosis (LDL); exocytosis releases secretory products Gap junctions Connexon channels that allow ions and small molecules to pass directly between adjacent cells — electrical coupling in cardiac and smooth muscle Cell Signalling • Modes: endocrine (hormone via blood to distant targets), paracrine (local diffusion to neighbouring cells), autocrine (acts on the secreting cell itself), juxtacrine/contact-dependent, and synaptic (neurotransmitter across a synapse). • Receptor types: ion-channel-linked (ionotropic) — fast, milliseconds, e.g. the nicotinic acetylcholine receptor;

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G-protein-coupled (GPCR, metabotropic) — seven transmembrane domains acting through second messengers; enzyme-linked — receptor tyrosine kinases for insulin and growth factors; and intracellular/nuclear receptors for lipid-soluble steroid and thyroid hormones, which act as transcription factors and are therefore slow but long-lasting. • Second messengers: cyclic AMP (adenylyl cyclase → protein kinase A), cyclic GMP, IP₃ and DAG (phospholipase C → Ca²⁺ release and protein kinase C) and Ca²⁺ itself.

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The cascade gives enormous signal amplification. • Signalling ends by degradation of the ligand, receptor internalisation and desensitisation, and hydrolysis of the second messenger (phosphodiesterase).

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Immunology • Innate (non-specific) immunity is present from birth, acts immediately, and has no memory: physical and chemical barriers (skin, mucus, lysozyme, acid), phagocytes (neutrophils, macrophages), natural killer cells, complement, interferons, inflammation and fever. • Adaptive (specific) immunity is acquired, slower on first exposure, antigen-specific and has memory.

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It is humoral — B lymphocytes maturing in the bone marrow into plasma cells that secrete antibodies against extracellular pathogens — and cell-mediated — T lymphocytes maturing in the thymus, comprising helper T (CD4), cytotoxic T (CD8), regulatory and memory T cells, acting against intracellular pathogens, tumour and transplanted cells. • Active immunity is produced by the person's own immune response (natural infection or vaccination) — slow to develop but long-lasting with memory; passive immunity is the transfer of ready-made antibodies (maternal IgG across the placenta, IgA in milk, antisera and immunoglobulin injections) — immediate but temporary and without memory. • Antigen: any substance that can be recognised by the immune system and provoke a response; the small part actually recognised is the epitope (antigenic determinant).

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A hapten is too small to be immunogenic alone and must be coupled to a carrier protein. • Antibody (immunoglobulin): a Y-shaped glycoprotein of two heavy and two light chains with variable regions forming two antigen-binding sites (Fab) and a constant Fc region.

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The five classes are IgG (most abundant, ~75-80 %, the only one crossing the placenta, secondary response), IgM (pentamer, largest, first produced in the primary response, best complement activator), IgA (dimer in secretions, milk, saliva, tears), IgE (allergy and parasites, binds mast cells) and IgD (B-cell receptor). • Antigen-antibody reactions: precipitation (soluble antigen — the basis of immunodiffusion and immunoelectrophoresis), agglutination (particulate antigen — blood grouping, latex tests), neutralisation of toxins and viruses, opsonisation and complement fixation, and labelled assays — ELISA, RIA, immunofluorescence and the lateral-flow immunoassay, which are the working principles of most biomedical diagnostic instruments.

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The reaction is specific, reversible and non-covalent, and requires the correct antigen-to-antibody ratio (the zone of equivalence) for visible precipitation.

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This section covers the composition and functions of blood, the formed elements, haematopoiesis, haemostasis and the coagulation cascade, DNA, RNA and protein synthesis, and the techniques of genetic engineering.

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Composition of Blood • Blood is a fluid connective tissue of about 5-6 litres in an adult (7-8 % of body weight), consisting of plasma (~55 %) and formed elements (~45 %).

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The packed cell volume is the haematocrit — about 45 % in men and 40 % in women.

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Blood pH is 7.35-7.45 and its viscosity is about 3-5 times that of water. • Plasma is about 91-92 % water with 7-8 % plasma proteins — albumin (most abundant; maintains colloid osmotic (oncotic) pressure and transports substances), globulins (α and β transport, γ = antibodies) and fibrinogen (clotting) — plus electrolytes, nutrients, wastes, gases and hormones.

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Serum is plasma without fibrinogen and the clotting factors, i.e. what remains after clotting. • Functions of blood: transport of O₂, CO₂, nutrients, wastes and hormones; regulation of pH, temperature and fluid balance; and protection through clotting and immunity.

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Formed element Normal count and features Function Erythrocyte (RBC) 4.5-5.5 million/μL; biconcave disc ~7.5 μm, no nucleus or mitochondria in mammals, life span 120 days, contains haemoglobin (13-18 g/dL) Transport of O₂ (and some CO₂); the biconcave shape maximises surface area and deformability Leukocyte (WBC) 4,000-11,000/μL; nucleated Defence — see the differential below Platelet (thrombocyte) 150,000-400,000/μL; cell fragments of megakaryocytes, life span 8-10 days Haemostasis — adhesion, aggregation and release of clotting mediators • Leukocyte differential (remember 'Never Let Monkeys Eat Bananas' in order of decreasing frequency):

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Neutrophils 60-70 % (first responders, phagocytosis of bacteria), Lymphocytes 20-30 % (B and T cells, specific immunity), Monocytes 2-8 % (become tissue macrophages), Eosinophils 2-4 % (parasites and allergy) and Basophils 0.5-1 % (release histamine and heparin).

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The first three plus eosinophils and basophils divide into granulocytes (neutrophil, eosinophil, basophil) and agranulocytes (lymphocyte, monocyte). • Haemoglobin is a tetramer of four globin chains (2α + 2β in HbA), each with a haem group containing Fe²⁺, so one haemoglobin molecule carries four O₂ molecules.

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Carbon monoxide binds with about 200-250 times the affinity of oxygen, which is the basis of CO poisoning and of pulse-oximeter error. • Blood groups: the ABO system (antigen on the RBC, naturally occurring antibody in the plasma — group O is the universal donor of red cells and AB the universal recipient) and the Rh system (D antigen; an Rh-negative mother carrying an Rh-positive fetus may be sensitised, causing haemolytic disease of the newborn, prevented by anti-D immunoglobulin).

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Haematopoiesis • Haematopoiesis is the formation of blood cells.

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Sites change with age: yolk sac in the early embryo → liver and spleen in the fetus → red bone marrow after birth; in the adult it is confined to the flat bones (sternum, ribs, pelvis, vertebrae, skull) and the proximal ends of the femur and humerus. • All blood cells derive from a single pluripotent haematopoietic stem cell (HSC), which is self-renewing and multipotent and carries the marker CD34.

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It gives rise to a myeloid progenitor (erythrocytes, platelets via megakaryocytes, granulocytes and monocytes) and a lymphoid progenitor (B, T and NK cells). • Regulation is by growth factors: erythropoietin (EPO) from the kidney in response to hypoxia drives erythropoiesis; thrombopoietin from the liver drives platelet production;

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G-CSF and GM-CSF drive granulocyte and monocyte production.

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Iron, vitamin B₁₂ and folate are essential raw materials. • Erythrocyte destruction: after about 120 days, macrophages of the spleen and liver break down haemoglobin — globin to amino acids, iron recycled, and haem to biliverdin then bilirubin, which is conjugated in the liver and excreted in bile; excess gives jaundice. • Clinical/engineering relevance:

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HSC transplantation (bone marrow transplant), stem-cell processing and cryopreservation, cell counters and flow cytometry, and the manufacture of recombinant EPO and G-CSF.

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Haemostasis and the Coagulation Cascade • Haemostasis — the arrest of bleeding — proceeds in three steps:

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(1) vascular spasm (vasoconstriction);

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(2) formation of the platelet plug — platelets adhere to exposed collagen via von Willebrand factor, become activated, change shape and release ADP and thromboxane A₂, and aggregate (primary haemostasis); and (3) coagulation — formation of a fibrin mesh that stabilises the plug (secondary haemostasis).

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Afterwards come clot retraction and fibrinolysis. • Clotting factors are numbered I to XIII (there is no factor VI):

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I fibrinogen, II prothrombin, III tissue factor/thromboplastin, IV calcium ions, V labile factor, VII stable factor, VIII antihaemophilic factor, IX Christmas factor, X Stuart-Prower factor, XI plasma thromboplastin antecedent, XII Hageman (contact) factor, XIII fibrin-stabilising factor.

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Most are made in the liver, and factors II, VII, IX and X are vitamin K dependent — the target of warfarin. • Extrinsic pathway: triggered by tissue factor (III) released from damaged tissue, which with factor VII and Ca²⁺ activates factor X.

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It is fast (seconds) and is assessed by the prothrombin time (PT/INR). • Intrinsic pathway: triggered by contact activation of factor XII on a damaged surface (or on glass or a foreign biomaterial), proceeding XII → XI → IX, which with VIII, Ca²⁺ and platelet phospholipid activates factor X.

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It is slower (minutes) and is assessed by the activated partial thromboplastin time (APTT). • Common pathway: both converge on factor X → Xa, which with factor V, Ca²⁺ and phospholipid forms prothrombinase; this converts prothrombin (II) → thrombin (IIa), which converts fibrinogen (I) → fibrin, and factor XIII cross-links the fibrin into a stable clot.

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Thrombin also amplifies the cascade by activating factors V, VIII, XI and platelets — a positive feedback loop. • Anticoagulation and fibrinolysis: natural inhibitors are antithrombin III (potentiated by heparin), protein C and S, and tissue factor pathway inhibitor; the intact endothelium itself is antithrombotic (prostacyclin, nitric oxide, thrombomodulin).

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Plasminogen → plasmin (by tPA) digests fibrin, producing D-dimer.

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In vitro, blood is anticoagulated by EDTA and citrate (which chelate Ca²⁺) or heparin. • Biomedical engineering relevance: every blood-contacting device — catheter, stent, dialysis membrane, oxygenator, heart valve, vascular graft — activates the intrinsic pathway on its surface, which is why surface engineering, heparin coating and systemic anticoagulation are central to device design (taken further in Chapter 2).

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DNA, RNA and Protein Synthesis • DNA structure (Watson and Crick, 1953): a right-handed double helix of two antiparallel strands with a sugar-phosphate backbone and complementary base pairing — adenine with thymine (2 hydrogen bonds), guanine with cytosine (3 hydrogen bonds).

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One full turn is 3.4 nm over 10 base pairs.

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Humans have 46 chromosomes (23 pairs) and about 3 billion base pairs with roughly 20,000-25,000 protein-coding genes. • The central dogma:

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DNA → (replication) → DNA → (transcription) → RNA → (translation) → protein, with reverse transcription (RNA → DNA, by reverse transcriptase in retroviruses) as the exception. • Replication is semi-conservative: helicase unwinds, primase lays an RNA primer, DNA polymerase extends only 5′ → 3′, giving a continuous leading strand and a discontinuous lagging strand of Okazaki fragments joined by ligase. • Transcription (in the nucleus):

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RNA polymerase reads the template strand and builds pre-mRNA; processing adds a 5′ cap and a poly-A tail and removes introns, splicing the exons together — alternative splicing lets one gene make several proteins. • Translation (on ribosomes): the genetic code is read in triplet codons; it is degenerate (several codons per amino acid), non-overlapping and almost universal.

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AUG (methionine) is the start codon and UAA, UAG and UGA are stop codons. tRNA carries the amino acid and pairs its anticodon with the mRNA codon; peptide bonds are formed as the ribosome moves along, and the chain then folds, often assisted by chaperones. • Mutations: point mutations may be silent, missense (sickle cell anaemia — a single base change giving valine for glutamate in β-globin) or nonsense; insertions and deletions that are not multiples of three cause a frameshift.

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Chromosomal disorders include trisomy 21 (Down syndrome); inheritance patterns are autosomal dominant, autosomal recessive (cystic fibrosis, thalassaemia) and X-linked recessive (haemophilia A, colour blindness).

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Techniques of Genetic Engineering Technique Principle and use Restriction enzymes Bacterial endonucleases cutting DNA at specific palindromic sites, giving sticky or blunt ends;

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DNA ligase joins fragments — the basis of recombinant DNA Vectors and cloning Plasmids, bacteriophages, cosmids and viral vectors carry the insert into a host (usually E. coli) which is then cultured; used to make recombinant insulin, human growth hormone, EPO, factor VIII and vaccines PCR Polymerase chain reaction — exponential amplification of a target sequence by repeated cycles of denaturation (~95 °C), annealing of primers (~55 °C) and extension by Taq polymerase (~72 °C); qPCR/real-time PCR quantifies, and RT-PCR starts from RNA (the basis of many diagnostic tests) Gel electrophoresis Separates nucleic acids (or proteins) by size in an electric field — DNA is negatively charged and migrates to the anode; smaller fragments travel further Blotting Southern = DNA, Northern = RNA, Western = protein (remember S-D, N-R, W-P) DNA sequencing Sanger chain-termination with dideoxynucleotides; next-generation sequencing for massively parallel, low-cost genomes Hybridisation and microarrays Labelled probes bind complementary sequences;

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DNA microarrays measure the expression of thousands of genes at once Gene editing CRISPR-Cas9 uses a guide RNA to direct a nuclease to a chosen sequence, allowing knockout or correction; earlier tools were ZFNs and TALENs Gene therapy and other Delivery of a functional gene by viral or non-viral vector; also transgenic animals, stem-cell engineering, DNA fingerprinting (STR analysis) and the Human Genome Project

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This section covers the microanatomy and types of neurons, impulse generation and conduction, neuromuscular transmission, the structure of the central nervous system, and the structure and physiology of the ear and the eye.

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The Neuron • A neuron is the structural and functional unit of the nervous system: excitable, conducting and, in humans, largely incapable of division.

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Its parts are the cell body (soma/perikaryon) containing the nucleus and Nissl granules (rough ER); dendrites, short branched processes that receive and carry impulses towards the cell body; and a single axon that carries impulses away, arising at the axon hillock (the trigger zone with the lowest threshold) and ending in synaptic terminals containing neurotransmitter vesicles. • Myelin is a lipid sheath formed by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system, interrupted at the nodes of Ranvier.

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It acts as an electrical insulator, giving saltatory conduction in which the impulse jumps from node to node — far faster and more energy-efficient than continuous conduction in unmyelinated fibres.

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Conduction velocity increases with fibre diameter and with myelination (about 0.5-2 m/s unmyelinated, up to 120 m/s in large myelinated fibres). • Neuroglia: astrocytes (support, blood-brain barrier, ion homeostasis), oligodendrocytes (CNS myelin), microglia (immune/phagocytic), ependymal cells (line the ventricles, make cerebrospinal fluid) and Schwann and satellite cells in the PNS.

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Glia outnumber neurons but are not excitable.

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Classification Types By structure (processes) Unipolar/pseudounipolar (sensory ganglia), bipolar (retina, olfactory, cochlear), multipolar (the commonest — motor neurons and most CNS neurons), anaxonic By function Sensory (afferent) — towards the CNS; motor (efferent) — away from the CNS to effectors; interneurons (association) — between the two, over 90 % of CNS neurons Arrangement Nucleus/ganglion = a collection of cell bodies in the CNS/PNS; tract/nerve = a bundle of axons in the CNS/PNS; grey matter = cell bodies, white matter = myelinated axons Impulse Generation and Conduction • Resting membrane potential ≈ −70 mV (inside negative), produced by the Na⁺/K⁺-ATPase, the much greater resting permeability to K⁺ than to Na⁺, and trapped intracellular anions.

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The equilibrium potential of a single ion is given by the Nernst equation, E = (RT/zF)·ln([out]/[in]), and the overall potential by the Goldman-Hodgkin-Katz equation. • Action potential: a stimulus depolarises the membrane; on reaching the threshold of about −55 mV, voltage-gated Na⁺ channels open and Na⁺ rushes in, giving rapid depolarisation to about +30 to +40 mV.

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The Na⁺ channels then inactivate and voltage-gated K⁺ channels open, giving repolarisation, usually with a brief hyperpolarisation (undershoot) before the pump restores the resting state.

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The whole event lasts about 1 ms in a nerve fibre. • Principles: the impulse is all-or-none — below threshold nothing happens, above it the amplitude is constant; stimulus strength is coded by frequency, not amplitude.

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During the absolute refractory period no second impulse is possible (which sets the maximum firing rate and makes conduction one-way), and during the relative refractory period a stronger-than-normal stimulus is needed. • Synaptic transmission: the impulse reaches the terminal → voltage-gated Ca²⁺ channels open → vesicles fuse and release neurotransmitter by exocytosis → it diffuses across the synaptic cleft (~20 nm) and binds post-synaptic receptors → an EPSP (excitatory, depolarising — glutamate, acetylcholine) or an IPSP (inhibitory, hyperpolarising — GABA, glycine) is produced, and these are summed spatially and temporally at the axon hillock.

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Transmission is unidirectional and subject to delay, fatigue and drug action.

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Major transmitters: acetylcholine, noradrenaline, dopamine, serotonin, glutamate, GABA, glycine and the endorphins.

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Neuromuscular Transmission • The neuromuscular junction (motor end plate) is the synapse between a motor neuron and a skeletal muscle fibre; the neuron plus all the fibres it supplies is a motor unit. • Sequence: action potential reaches the terminal → Ca²⁺ influx → release of acetylcholine → binding to nicotinic ACh receptors on the junctional folds → a large end-plate potential → muscle action potential spreading along the sarcolemma and down the T-tubules → Ca²⁺ release from the sarcoplasmic reticulum → Ca²⁺ binds troponin C, tropomyosin moves, and the sliding-filament cross-bridge cycle between actin and myosin (powered by ATP) shortens the sarcomere.

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Relaxation follows when Ca²⁺ is pumped back and acetylcholinesterase hydrolyses the transmitter. • Pharmacology and pathology: curare blocks the receptor competitively, succinylcholine causes depolarising block, organophosphates and neostigmine inhibit acetylcholinesterase, botulinum toxin prevents ACh release, and myasthenia gravis is an autoimmune attack on the ACh receptor.

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This junction is the target of muscle relaxants in anaesthesia and the physiological basis of EMG recording and functional electrical stimulation.

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Structure of the Central Nervous System • The nervous system divides into the CNS (brain and spinal cord) and the PNS (cranial and spinal nerves and ganglia); functionally the PNS is somatic (voluntary) and autonomic (involuntary), the latter comprising the sympathetic ('fight or flight', thoracolumbar, noradrenaline) and parasympathetic ('rest and digest', craniosacral, acetylcholine) divisions. • Brain: the cerebrum, with two hemispheres of folded cortex (gyri and sulci) joined by the corpus callosum and divided into frontal (motor, personality, Broca's speech area), parietal (somatosensory), temporal (hearing, Wernicke's area, memory) and occipital (vision) lobes; the diencephalon — thalamus (relay for all sensation except smell) and hypothalamus (homeostasis, temperature, hunger, thirst, autonomic and endocrine control); the cerebellum (balance, coordination, muscle tone); and the brain stem — midbrain, pons and medulla oblongata, which contains the cardiac, vasomotor and respiratory centres and is therefore vital. • Spinal cord: runs from the medulla to about L1-L2, with 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal).

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In cross-section the grey matter is central and H-shaped with the white matter outside — the reverse of the cerebrum.

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The dorsal root is sensory and the ventral root motor (the Bell-Magendie law).

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It conducts ascending and descending tracts and mediates reflexes. • Protection: the skull and vertebrae, the three meninges (dura, arachnoid, pia mater), cerebrospinal fluid (about 150 mL, made by the choroid plexus, cushioning and nourishing the CNS) and the blood-brain barrier.

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Cerebral electrical activity recorded from the scalp gives the EEG, with the delta, theta, alpha and beta rhythms.

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The Ear and the Physiology of Hearing • External ear: the pinna (auricle) collects sound and the external auditory canal conducts it to the tympanic membrane (eardrum), which vibrates. • Middle ear: an air-filled cavity containing the three ossicles — malleus, incus and stapes — which transmit and amplify vibration from the eardrum to the oval window.

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The gain comes from the area ratio of the tympanic membrane to the oval window (about 17:1) and the lever action of the ossicles (about 1.3:1), together roughly 22-25 times, which matches the low impedance of air to the high impedance of cochlear fluid — impedance matching.

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The Eustachian (pharyngotympanic) tube equalises pressure with the pharynx. • Inner ear: the bony and membranous labyrinth — the cochlea for hearing and the vestibular apparatus (three semicircular canals, utricle and saccule) for balance and acceleration.

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The cochlea is a spiral of about 2.75 turns with three ducts: scala vestibuli and scala tympani (containing perilymph) and the scala media (cochlear duct, containing endolymph), which holds the organ of Corti on the basilar membrane, with inner and outer hair cells under the tectorial membrane. • Mechanism: stapes movement at the oval window sets up a travelling wave in the cochlear fluid; the basilar membrane is narrow and stiff at the base (responding to high frequencies) and wide and floppy at the apex (low frequencies), so each frequency peaks at a particular place — the place theory of tonotopic coding.

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Deflection of the stereocilia opens mechanically gated channels, depolarising the hair cell, releasing transmitter and firing the cochlear (VIII) nerve; the round window relieves the pressure. • Range and engineering relevance: human hearing spans about 20 Hz to 20 kHz, with greatest sensitivity at 1-4 kHz and a threshold of 0 dB SPL = 20 μPa.

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Conductive deafness (external or middle ear) is distinguished from sensorineural deafness (cochlea or nerve) by tuning-fork and audiometric tests.

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This physiology underlies pure-tone audiometry, tympanometry, otoacoustic emissions, hearing aids and the cochlear implant, which stimulates the auditory nerve electrode-by-electrode according to the tonotopic map.

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The Eye and the Physiology of Vision • Three coats: the fibrous outer coat — the opaque protective sclera and the transparent cornea, which provides about two-thirds of the eye's total refractive power (~40 of ~60 dioptres); the vascular middle coat (uvea) — choroid, ciliary body and iris, the last controlling pupil size; and the retina, the nervous inner coat. • Refractive media: cornea → aqueous humour (secreted by the ciliary body, draining through the trabecular meshwork and canal of Schlemm — obstruction raises intraocular pressure and causes glaucoma; normal IOP is about 10-21 mmHg) → lens → vitreous humour. • Retina: the photoreceptors are rods (about 120 million, highly sensitive, used in dim light, no colour, contain rhodopsin, concentrated peripherally) and cones (about 6 million, need bright light, give colour and high acuity, three types for red, green and blue, packed at the fovea centralis in the macula, the point of sharpest vision).

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The optic disc, where the optic nerve leaves, has no receptors and is the blind spot.

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Signals pass photoreceptor → bipolar cell → ganglion cell → optic nerve (II) → optic chiasma (nasal fibres cross) → lateral geniculate body → occipital visual cortex. • Accommodation: to focus on a near object the ciliary muscle contracts, the suspensory ligaments (zonules) slacken and the lens becomes more convex, increasing its power; the pupil constricts and the eyes converge.

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With age the lens stiffens, giving presbyopia. • Refractive errors: myopia (short sight — image focused in front of the retina, corrected by a concave/diverging lens), hypermetropia (long sight — corrected by a convex/converging lens), astigmatism (unequal curvature — cylindrical lens) and presbyopia.

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Cataract is opacity of the lens. • Engineering relevance: visual acuity charts, tonometry, slit lamp, ophthalmoscopy, fundus photography, optical coherence tomography (OCT), perimetry, electroretinography (ERG) and the visual evoked potential, and prosthetic work on retinal implants — all of which appear again in the instrumentation chapters.

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This section covers the anatomy of the heart and blood vessels, coronary and systemic circulation, the cardiac cycle, cardiac output and blood pressure, the conduction system of the heart, the respiratory tract and lungs, the mechanism and control of breathing, lung volumes, and gas transfer.

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Anatomy of the Heart and Blood Vessels • The heart is a four-chambered muscular pump of about 300 g in the mediastinum.

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The right atrium and ventricle handle deoxygenated blood and the left atrium and ventricle oxygenated blood; the left ventricular wall is about three times thicker because it pumps against the high resistance of the systemic circulation. • Valves: the atrioventricular valves — tricuspid (right) and mitral/bicuspid (left), anchored by chordae tendineae to papillary muscles to prevent prolapse; and the semilunar valves — pulmonary and aortic.

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All valves ensure one-way flow, and their closure produces the heart sounds:

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S1 ('lub') = closure of the AV valves at the start of systole and S2 ('dub') = closure of the semilunar valves at the start of diastole. • Wall layers: endocardium, myocardium and epicardium, enclosed in the pericardium with a little fluid in the pericardial cavity. • Circulations: the pulmonary circuit — right ventricle → pulmonary artery (the only artery carrying deoxygenated blood) → lungs → pulmonary veins → left atrium; and the systemic circuit — left ventricle → aorta → body → venae cavae → right atrium.

6

Blood flows in series through both, so their outputs must be equal. • Vessels: arteries (thick elastic and muscular walls, carry blood away from the heart, act as a pressure reservoir — the Windkessel effect that smooths pulsatile flow), arterioles (the chief site of peripheral resistance and hence of blood-pressure control), capillaries (one endothelial cell thick, the site of exchange, with the greatest total cross-sectional area and therefore the slowest flow), venules and veins (thin-walled, valved, the capacitance vessels holding about 60-70 % of the blood volume). • Coronary circulation: the right and left coronary arteries are the first branches of the aorta, arising just above the aortic valve; the left divides into the left anterior descending and circumflex branches.

7

Venous return is by the coronary sinus into the right atrium.

8

Coronary flow occurs mainly during diastole, because during systole the contracting myocardium compresses its own vessels — which is why tachycardia, by shortening diastole, reduces coronary perfusion.

9

The coronary arteries are functional end arteries, so occlusion causes myocardial infarction.

10

Conduction System of the Heart • Order:

11

SA node → internodal pathways → AV node → bundle of His → right and left bundle branches → Purkinje fibres → ventricular myocardium. • The sino-atrial (SA) node, in the right atrial wall near the opening of the superior vena cava, is the natural pacemaker at 60-100 impulses/min, simply because it has the fastest rate of spontaneous depolarisation.

12

Latent pacemakers are the AV node (40-60/min) and the Purkinje system (20-40/min). • The AV node introduces a deliberate delay of about 0.1 s, allowing the atria to finish emptying before the ventricles contract, and it is the only normal electrical connection between atria and ventricles (the fibrous skeleton insulating them elsewhere). • Cardiac muscle is a functional syncytium coupled by gap junctions in the intercalated discs, has a long action potential (~200-300 ms) with a plateau phase due to slow Ca²⁺ influx, and therefore a long refractory period that prevents tetanus — the property that makes rhythmic pumping possible.

13

Its contraction is myogenic: the heart beats without nerve supply, the autonomic nerves only modulating rate and force (sympathetic increases both, vagal parasympathetic slows the rate). • The ECG is the body-surface record of this activity: the P wave = atrial depolarisation, the QRS complex = ventricular depolarisation (atrial repolarisation is hidden within it) and the T wave = ventricular repolarisation.

14

The PR interval (0.12-0.20 s) measures AV conduction, the QRS duration (< 0.12 s) ventricular conduction, and the QT interval the total ventricular electrical event.

15

This is the foundation of Chapter 3's instrumentation, and of pacemakers and defibrillators.

16

The Cardiac Cycle • One cardiac cycle at a heart rate of 75/min lasts 0.8 s, made up of atrial systole (0.1 s), ventricular systole (0.3 s) and diastole (0.4 s) — so the heart rests longer than it works, and diastole shortens disproportionately as rate rises. • Phases: atrial systole (tops up the ventricle with the final 20-30 % of its filling) → isovolumetric contraction (all valves shut, pressure rises steeply, no change in volume, S1 heard) → ejection (aortic/pulmonary valves open, blood is expelled) → isovolumetric relaxation (all valves shut again, S2 heard, the dicrotic notch appears on the aortic pressure trace) → rapid and then slow ventricular filling (diastasis) once the AV valves open. • Volumes: end-diastolic volume (EDV) ≈ 120-130 mL, end-systolic volume (ESV) ≈ 50-60 mL, stroke volume SV = EDV − ESV ≈ 70 mL, and ejection fraction EF = SV/EDV ≈ 55-70 % (a key clinical index of ventricular function).

17

Cardiac Output and Blood Pressure • Cardiac output CO = heart rate × stroke volume ≈ 75 × 70 mL ≈ 5-5.5 L/min at rest, rising to 20-25 L/min in exercise.

18

Cardiac index is CO divided by body surface area (about 3 L/min/m²). • Determinants of stroke volume: preload (end-diastolic stretch — by the Frank-Starling law, the greater the initial fibre length, the more forceful the contraction, which automatically matches the outputs of the two ventricles), afterload (the resistance against which the ventricle must eject) and contractility (the intrinsic inotropic state, increased by sympathetic stimulation and by drugs such as digoxin). • Blood pressure: normal adult 120/80 mmHg.

19

Pulse pressure = systolic − diastolic (≈ 40 mmHg), and the mean arterial pressure MAP = diastolic + ⅓(pulse pressure) ≈ 93 mmHg (the ⅓ weighting because diastole occupies two-thirds of the cycle).

20

The governing relation is MAP = CO × total peripheral resistance, the haemodynamic form of Ohm's law; resistance follows Poiseuille's law, R = 8ηL/(πr⁴), so resistance varies inversely with the fourth power of the radius — halving the radius multiplies the resistance sixteen-fold, which is why arteriolar tone dominates blood-pressure control. • Regulation: short-term by the baroreceptors of the carotid sinus and aortic arch acting through the vasomotor centre, and by chemoreceptors; long-term by the kidney through blood volume and the renin-angiotensin-aldosterone system, with ADH and ANP.

21

Measurement is by the auscultatory (Korotkoff sound) method with a sphygmomanometer, by oscillometry in automatic monitors, and invasively by an arterial line.

22

The Respiratory Tract and Lungs • Upper respiratory tract: nose and nasal cavity (filtering, warming and humidifying the air), pharynx (naso-, oro- and laryngopharynx) and larynx (voice box, with the vocal cords and the epiglottis, which closes the airway during swallowing). • Lower tract: trachea (held open by C-shaped cartilage rings, dividing at the carina at about T4-T5) → main bronchi (the right is wider, shorter and more vertical, so inhaled foreign bodies usually enter it) → lobar and segmental bronchi → bronchioles → terminal bronchioles (the end of the conducting zone, the anatomical dead space of about 150 mL) → respiratory bronchioles, alveolar ducts and alveoli (the respiratory zone where exchange occurs). • Lungs: the right lung has three lobes and two fissures, the left has two lobes and one fissure plus the cardiac notch; there are about 300 million alveoli giving a gas-exchange surface of 70-100 m².

23

The respiratory membrane is only about 0.5 μm thick — alveolar epithelium, fused basement membranes and capillary endothelium.

24

Type I pneumocytes form the thin exchange surface and type II pneumocytes secrete surfactant, which lowers surface tension, prevents alveolar collapse and reduces the work of breathing (its deficiency causes respiratory distress syndrome in the newborn). • Pleura and pleural cavity: the visceral pleura covers the lung and the parietal pleura lines the thoracic wall, with a thin film of fluid between them.

25

The intrapleural pressure is negative (about −4 mmHg at rest, −8 mmHg at full inspiration), which is what keeps the lungs expanded against their elastic recoil; loss of this negative pressure by air entering the cavity is a pneumothorax, in which the lung collapses.

26

Mechanism, Volumes and Control of Breathing • Mechanism: inspiration is active — the diaphragm (the principal muscle, supplied by the phrenic nerve, C3-C5) descends and the external intercostals raise the ribs, enlarging the thorax, lowering intrapulmonary pressure below atmospheric, so air flows in.

27

Quiet expiration is passive, by elastic recoil of the lungs and chest wall; forced expiration uses the abdominal muscles and internal intercostals.

28

Types of breathing: abdominal/diaphragmatic (predominant in men and in quiet breathing), thoracic/costal (predominant in women) and forced or accessory breathing. • Compliance (ΔV/ΔP) measures the distensibility of the lung, reduced in fibrosis and increased in emphysema; airway resistance follows the same fourth-power law as blood vessels and rises in asthma and COPD. • Lung volumes (typical adult male): tidal volume TV = 500 mL, inspiratory reserve volume IRV ≈ 3,000 mL, expiratory reserve volume ERV ≈ 1,100 mL, residual volume RV ≈ 1,200 mL.

29

IC = TV + IRV ≈ 3,500;

30

FRC = ERV + RV ≈ 2,300;

31

VC = TV + IRV + ERV ≈ 4,600;

32

TLC = VC + RV ≈ 5,800 mL.

33

Residual volume, FRC and TLC cannot be measured by spirometry and require helium dilution, nitrogen washout or body plethysmography. • Ventilation: minute ventilation = TV × respiratory rate ≈ 500 × 12 = 6 L/min; alveolar ventilation = (TV − dead space) × rate ≈ (500 − 150) × 12 = 4.2 L/min — the physiologically useful figure, which is why slow deep breathing ventilates far better than rapid shallow breathing.

34

FEV₁/FVC > 0.7 is normal; a low ratio indicates an obstructive defect and a proportionate reduction of both an restrictive defect. • Control: the respiratory centres in the medulla (dorsal and ventral groups) and pons (pneumotaxic and apneustic centres) set the rhythm automatically.

35

The strongest normal stimulus is a rise in arterial PCO₂ (and the consequent fall in CSF pH), acting on the central chemoreceptors of the medulla; the peripheral chemoreceptors of the carotid and aortic bodies respond mainly to a fall in PO₂ below about 60 mmHg, which becomes the driving stimulus in chronic CO₂ retention.

36

The Hering-Breuer reflex limits over-inflation. • Gas transfer and diffusion: exchange is by passive diffusion down partial-pressure gradients, governed by Fick's law — rate ∝ area × diffusion coefficient × pressure difference / thickness.

37

Typical values: alveolar PO₂ 100 mmHg and PCO₂ 40 mmHg; venous blood arriving at PO₂ 40 and PCO₂ 46 mmHg.

38

CO₂ diffuses about 20 times faster than O₂ because of its much greater solubility, so hypercapnia is a later sign than hypoxia in diffusion defects. • Transport: oxygen is carried ~98 % bound to haemoglobin as oxyhaemoglobin and ~2 % dissolved; the oxygen-haemoglobin dissociation curve is sigmoid, and it shifts right (releasing more O₂ to the tissues) with a rise in temperature, CO₂, H⁺ (fall in pH — the Bohr effect) and 2,3-DPG.

39

Carbon dioxide is carried ~70 % as bicarbonate (formed by carbonic anhydrase in the red cell, with the chloride shift), ~23 % as carbamino compounds and ~7 % dissolved.

40

This sigmoid curve is exactly why pulse oximetry saturation falls slowly at first and then precipitously.

1

This section covers the metabolic functions of the urinary system, the topography and microanatomy of the kidney, the structure-function relationship of the ureter, bladder and urethra, and the control of bladder function.

2

Functions of the Urinary System • The urinary system consists of two kidneys, two ureters, the urinary bladder and the urethra.

3

Its functions are: • Excretion of metabolic wastes — urea (from protein), creatinine (from muscle), uric acid (from nucleic acids), drugs and toxins. • Regulation of water and electrolyte balance and hence of blood volume and blood pressure (with ADH, aldosterone and ANP). • Acid-base regulation — excretion of H⁺ and reabsorption/generation of bicarbonate; together with the lungs, the kidney holds arterial pH at 7.35-7.45. • Endocrine functions — secretion of erythropoietin (red-cell production), renin (the renin-angiotensin-aldosterone system) and activation of vitamin D to calcitriol (calcium metabolism). • Metabolic functions — gluconeogenesis during prolonged fasting, and catabolism of peptide hormones such as insulin.

4

Topography of the Kidneys • The kidneys are paired, bean-shaped, retroperitoneal organs lying against the posterior abdominal wall at about the level of T12 to L3; the right kidney sits slightly lower than the left because of the liver.

5

Each is about 11 × 6 × 3 cm and weighs 130-150 g, and is surrounded by a fibrous capsule, perirenal fat and the renal fascia.

6

The hilum on the medial (concave) side transmits, from front to back, the renal vein, renal artery and renal pelvis (VAP).

7

The adrenal gland caps the upper pole. • In section the kidney shows an outer cortex and an inner medulla containing 8-18 renal pyramids, whose apices (papillae) open into minor calyces → major calyces → renal pelvis → ureter.

8

Columns of cortex run between the pyramids. • Blood supply: renal artery → segmental → interlobar → arcuate → interlobular → afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries and vasa recta → veins.

9

The kidneys receive about 20-25 % of the resting cardiac output (about 1.2 L/min) for their weight of only 0.5 % of the body — an extraordinary perfusion that exists for filtration, not for their own metabolism.

10

The presence of two capillary beds in series is what makes filtration followed by reabsorption possible.

11

Microanatomy: the Nephron • The nephron is the structural and functional unit of the kidney; there are about 1 to 1.3 million per kidney.

12

Cortical nephrons (~85 %) have short loops; juxtamedullary nephrons (~15 %) have long loops of Henle descending deep into the medulla and are responsible for concentrating the urine. • Parts: the renal corpuscle — a glomerulus (a tuft of fenestrated capillaries) inside Bowman's capsule, whose visceral layer of podocytes with their filtration slits forms, with the fused basement membrane, the three-layered filtration barrier — followed by the proximal convoluted tubule, the loop of Henle (descending and ascending limbs), the distal convoluted tubule and the collecting duct. • The three renal processes: glomerular filtration, tubular reabsorption and tubular secretion; urine = filtered − reabsorbed + secreted. • Glomerular filtration is driven by the net filtration pressure = glomerular capillary hydrostatic pressure (~55 mmHg) − capsular hydrostatic pressure (~15) − blood colloid osmotic pressure (~30) ≈ 10 mmHg.

13

The glomerular filtration rate (GFR) is about 125 mL/min, i.e.

14

180 L/day, of which over 99 % is reabsorbed, leaving about 1.5 L of urine.

15

The barrier is size- and charge-selective: water, ions, glucose, amino acids and urea pass freely, while cells and plasma proteins (especially albumin, which is negatively charged) do not — their appearance in urine signals glomerular disease.

16

GFR is held steady over a wide range of blood pressure by autoregulation (myogenic response and tubuloglomerular feedback via the juxtaglomerular apparatus, which combines the macula densa of the distal tubule with the renin-secreting juxtaglomerular cells of the afferent arteriole). • Tubular function by segment: the proximal convoluted tubule reabsorbs about 65-70 % of the filtrate and essentially all the glucose and amino acids (by Na⁺-coupled secondary active transport — glucose appears in urine only when the plasma level exceeds the renal threshold of about 180 mg/dL, as in diabetes); the descending limb is permeable to water only and the thick ascending limb to salt only (the Na⁺-K⁺-2Cl⁻ symporter, blocked by loop diuretics), which together with the vasa recta create the counter-current multiplier and exchanger that make the medulla hyperosmotic; the distal tubule and collecting duct perform the fine, hormonally controlled adjustment — aldosterone promoting Na⁺ reabsorption and K⁺ secretion, and ADH (vasopressin) inserting aquaporins to reabsorb water and concentrate the urine. • Clearance and its engineering relevance: renal clearance C = (U × V)/P; inulin clearance equals GFR exactly, and creatinine clearance is its practical clinical approximation.

17

This whole physiology is the basis of haemodialysis and peritoneal dialysis, the artificial kidney being a counter-current device relying on diffusion, ultrafiltration and convection across a semipermeable membrane.

18

Ureter, Bladder and Urethra Structure Form and function Ureter A muscular tube 25-30 cm long from renal pelvis to bladder, retroperitoneal, with a transitional epithelium lining and smooth muscle that propels urine by peristalsis — flow is therefore active, not gravity-dependent.

19

It has three normal constrictions (pelvi-ureteric junction, crossing of the pelvic brim/iliac vessels, and the vesico-ureteric junction) where stones commonly lodge.

20

Its oblique passage through the bladder wall acts as a valve preventing reflux when the bladder fills Urinary bladder A distensible pelvic reservoir of 400-500 mL functional capacity, lined by transitional epithelium (urothelium) whose umbrella cells flatten on filling; its wall is the detrusor muscle of interlacing smooth muscle.

21

The trigone, between the two ureteric orifices and the internal urethral orifice, is smooth and fixed.

22

The bladder is remarkably compliant — pressure stays low (< 10-15 cmH₂O) until it is nearly full Urethra Conveys urine out.

23

3-4 cm, straight, opening in the vestibule — the shortness explains the far higher incidence of urinary tract infection.

24

18-20 cm, with prostatic, membranous and spongy (penile) parts, and it carries both urine and semen.

25

Two sphincters: the internal urethral sphincter of smooth muscle (involuntary, sympathetic) and the external urethral sphincter of skeletal muscle (voluntary, pudendal nerve) Control of Bladder Function (Micturition) • Storage (filling) phase: as the bladder fills, sympathetic outflow (T11-L2, the hypogastric nerve) relaxes the detrusor and contracts the internal sphincter, and the somatic pudendal nerve (S2-S4) keeps the external sphincter closed.

26

Compliance keeps intravesical pressure low. • Micturition reflex: stretch receptors in the detrusor discharge at a volume of about 300-400 mL, giving the sensation of fullness; afferents travel to the sacral micturition centre (S2-S4), and parasympathetic (pelvic nerve) outflow contracts the detrusor while the sphincters relax.

27

It is a spinal reflex under higher control from the pontine micturition centre and the frontal cortex, which allows voluntary postponement or initiation — the basis of continence, which is learned in childhood. • Disorders and engineering relevance: a spinal cord lesion above the sacral centre produces an automatic (reflex/neurogenic) bladder that empties without voluntary control, while a lesion of the sacral centre or its nerves gives an atonic bladder with overflow incontinence; prostatic enlargement causes outflow obstruction and retention.

28

Clinical measurement is by urodynamics — cystometry (pressure-volume), uroflowmetry and electromyography of the sphincter — and the relevant devices include catheters, urinary stents, artificial sphincters and sacral neuromodulation.

1

This section covers the classification of human joints and the forces acting in them, the mechanics of hard tissue including bone growth and fracture mechanics, the mechanical properties of muscle, ligament and tendon, and the basics of blood rheology.

2

Classification of Human Joints Basis Types Structural Fibrous (sutures of the skull, syndesmosis, gomphosis — immovable or nearly so), cartilaginous (symphysis pubis, intervertebral discs — slightly movable) and synovial (freely movable, with a capsule, synovial membrane, synovial fluid and hyaline articular cartilage) Functional Synarthrosis (immovable), amphiarthrosis (slightly movable) and diarthrosis (freely movable) Synovial sub-types Ball and socket (shoulder, hip — 3 degrees of freedom), hinge (elbow, knee, ankle — 1 DOF), pivot (atlanto-axial, radio-ulnar), condyloid/ellipsoid (wrist — 2 DOF), saddle (thumb carpometacarpal) and plane/gliding (intercarpal, facet joints) • Articular cartilage is avascular, aneural and biphasic (a solid collagen-proteoglycan matrix saturated with fluid).

3

Its coefficient of friction against cartilage, lubricated by synovial fluid (rich in hyaluronic acid, a shear-thinning lubricant), is about 0.002-0.02 — lower than ice on ice, a figure no engineered bearing matches.

4

Lubrication is a combination of boundary, hydrodynamic, squeeze-film and weeping mechanisms. • Degrees of freedom and stability trade off: the shoulder has the greatest range and the least bony stability (hence dislocation), while the hip sacrifices range for a deep, stable socket.

5

Forces in Joints • Most human joints work as third-class levers, in which the muscle force (effort) is applied between the joint (fulcrum) and the load.

6

The muscle's moment arm is short and the load's moment arm long, so the mechanical advantage is less than one: the muscle must generate a force several times the load, and the joint reaction force is correspondingly large.

7

The compensating gain is speed and range of movement at the end of the limb. • Method of analysis: draw a free-body diagram of the segment, then apply ΣF = 0 and ΣM = 0 (static equilibrium) about the joint centre — a two-dimensional static analysis is usually enough for the examination. • Typical results to remember: holding a weight in the hand with the elbow flexed at 90°, the biceps force is roughly 7-10 times the weight held because its insertion is only about 5 cm from the joint while the hand is about 35 cm away.

8

In the shoulder, the deltoid acts at a very small angle, so abduction of the arm produces a joint force of about 1 body weight, rising sharply with a load in the hand.

9

In the hip, single-leg stance requires the abductors to balance the body weight about the femoral head, giving a joint reaction force of about 2.5-3 times body weight in walking and 4-5 times in running or stair climbing — which is why a walking stick in the opposite hand is so effective, and why hip prostheses are designed and tested to those loads.

10

In the knee, the patella acts as a pulley that increases the quadriceps moment arm, and the tibiofemoral force reaches about 3-4 times body weight in walking and much more in squatting.

11

The lumbar spine at L5-S1 carries about 2-3 times body weight in standing and can exceed 5-6 times when lifting incorrectly with a flexed back and extended arms, because the erector spinae have a moment arm of only about 5 cm. • Ankle and wrist: the ankle transmits about 3-5 times body weight during gait because of the small contact area and the calf muscle force; the wrist is a low-load but high-precision joint, the complexity of its carpal mechanics being a common source of implant failure.

12

Mechanics of Hard Tissue:

13

Bone • Composition: about 60-70 % mineral (hydroxyapatite, which gives stiffness and compressive strength), 20-25 % organic matrix (chiefly type I collagen, giving toughness and tensile strength) and 5-10 % water.

14

It is therefore a natural ceramic-polymer composite — and the classic exam point is that bone is strongest in compression, weaker in tension and weakest in shear. • Types: cortical (compact) bone — dense, about 5-10 % porosity, forming the shafts of long bones, built of osteons (Haversian systems); and cancellous (trabecular, spongy) bone — a porous lattice of trabeculae, 50-90 % porosity, in the ends of long bones and the vertebrae, where it absorbs energy and distributes load. • Cells: osteoblasts (form bone), osteocytes (mature cells in lacunae, the mechanosensors), osteoclasts (resorb bone) and osteoprogenitor cells. • Growth and development: bone forms by intramembranous ossification (flat bones of the skull, directly from mesenchyme) and endochondral ossification (long bones, from a hyaline cartilage model).

15

Long bones lengthen at the epiphyseal (growth) plate until it fuses, and grow in girth by appositional growth beneath the periosteum.

16

Bone is continuously remodelled throughout life. • Wolff's law: bone adapts its mass and architecture to the loads habitually placed on it — trabeculae align with the principal stress trajectories.

17

Hence disuse (bed rest, spaceflight) and stress shielding by an over-stiff implant cause bone loss, and this is the reason implant stiffness should approach that of bone.

18

Property Cortical bone Cancellous bone Density (apparent) About 1.8-2.0 g/cm³ 0.1-1.0 g/cm³ Porosity 5-10 % 50-90 % Young's modulus 15-20 GPa (longitudinal); about 10 GPa transverse 0.05-0.5 GPa Compressive strength ~150-200 MPa 2-12 MPa Tensile strength ~100-130 MPa Low Failure strain 1-3 % (relatively brittle) Up to 50 % by crushing — a good energy absorber Behaviour Anisotropic (stronger along the osteon axis) and viscoelastic (stiffer and stronger at higher strain rate) Anisotropic, strongly dependent on apparent density (E roughly proportional to density squared or cubed) • For comparison, stainless steel is about 200 GPa, titanium alloy 110 GPa, cobalt-chromium 210 GPa and PMMA bone cement 3 GPa — every metal implant is far stiffer than bone, which is the root of the stress-shielding problem taken up in Chapter 2.

19

Fracture Mechanics of Bone • Bone fails when the applied stress exceeds its strength, and the pattern of the fracture reveals the loading mode: transverse (bending or direct blow), oblique (compression combined with bending), spiral (torsion — the classic twisting injury), comminuted (high energy), avulsion (tension from a tendon or ligament), compression/crush (vertebral body) and greenstick (incomplete, in the more compliant bone of children). • Fracture-mechanics concepts: bone is a flaw-sensitive, quasi-brittle material.

20

Failure is governed by stress concentration at defects (a screw hole or a lytic lesion can reduce torsional strength by more than half) and by the stress intensity factor K reaching the fracture toughness KIC (about 2-12 MPa·m½ for cortical bone).

21

Toughening comes from crack deflection at cement lines, collagen fibre bridging and microcracking.

22

Fatigue from repeated sub-threshold loading produces stress fractures when microdamage outpaces remodelling, and osteoporosis (loss of bone mass with thinning and loss of connectivity of trabeculae) raises fracture risk far more than the loss of mass alone would suggest. • Healing: haematoma → inflammation → soft callus (fibrocartilage) → hard callus (woven bone) → remodelling into lamellar bone.

23

Primary (direct) healing without callus requires rigid compression fixation with almost no interfragmentary strain, while secondary healing with callus needs controlled micromotion — the principle behind modern flexible fixation and the reason fixation stiffness is a design decision, not simply a matter of making the plate as strong as possible.

24

Mechanics of Soft Tissue • Soft tissues are non-linear, anisotropic, viscoelastic and nearly incompressible.

25

Their tensile stress-strain curve has a characteristic toe region, in which the crimped collagen fibres straighten at low stress, followed by a stiff linear region, then yield and rupture.

26

Viscoelastic behaviour appears as creep (increasing strain under constant load), stress relaxation (falling stress at constant strain), hysteresis (energy loss in a loading-unloading cycle) and strain-rate dependence — they are stiffer and stronger when loaded rapidly. • Tendon connects muscle to bone; it is nearly parallel type I collagen, strong and stiff, with tensile strength about 50-100 MPa and a modulus of 1-2 GPa, failing at about 8-10 % strain.

27

Ligament connects bone to bone, has a less regular fibre arrangement with more elastin, and is therefore more extensible and slightly weaker — it must permit joint motion while restraining it at the limits and also contributes proprioception.

28

Both heal slowly because they are poorly vascularised. • Muscle: skeletal muscle generates active force by cross-bridge cycling and carries passive elastic force when stretched, the total being their sum.

29

Key relations are the length-tension curve — maximal active tension at the optimal sarcomere length where actin-myosin overlap is greatest, falling on either side — and the force-velocity curve — concentric force falls as shortening velocity rises (maximum force at zero velocity, i.e. isometric), while eccentric (lengthening) contraction develops the greatest force of all, which is why eccentric loading causes most muscle injury.

30

Maximum tetanic stress is about 20-40 N/cm² of physiological cross-sectional area.

31

Contraction types are isometric (no length change), isotonic (constant load) and isokinetic (constant velocity). • Other soft tissues worth knowing: articular cartilage (biphasic, creeps under sustained load as fluid exudes), the intervertebral disc (nucleus pulposus pressurised inside the annulus fibrosus, behaving hydrostatically), skin (highly non-linear, pre-stressed along Langer's lines) and the arterial wall (elastin at low strain, collagen at high strain, giving the characteristic J-shaped curve).

32

Blood Rheology • Rheology is the study of the deformation and flow of matter.

33

A Newtonian fluid has a constant viscosity independent of shear rate (water, plasma); blood is non-Newtonian. • Blood is a shear-thinning (pseudoplastic) suspension: its apparent viscosity falls as the shear rate rises, because at low shear rates red cells aggregate into rouleaux and at high shear rates they disaggregate, deform and align with the flow.

34

It also shows a small yield stress (the Casson model) and is thixotropic.

35

At high shear rates its viscosity approaches a constant, so blood may be treated as Newtonian in large arteries, but not in the microcirculation or in low-shear regions such as the venous system and recirculation zones of a device. • Determinants of viscosity: chiefly the haematocrit (the dominant factor — viscosity rises steeply above about 45 %, which is why polycythaemia causes sluggish flow and thrombosis), plus plasma protein concentration (especially fibrinogen, which promotes rouleaux), temperature (viscosity falls as temperature rises), red-cell deformability (lost in sickle-cell disease) and vessel diameter.

36

Whole-blood viscosity is about 3-4 mPa·s at high shear against about 1.2 mPa·s for plasma and 1 mPa·s for water at 37 °C. • Special effects in small vessels: the Fåhraeus-Lindqvist effect — apparent viscosity decreases in vessels below about 300 μm because red cells migrate to the axis leaving a cell-free plasma layer at the wall — reversing below about 5-7 μm, when cells must deform to pass.

37

The Fåhraeus effect is the accompanying fall in tube haematocrit. • Flow regimes: flow is normally laminar and pulsatile, with a roughly parabolic velocity profile in steady laminar flow and Womersley profiles when pulsatility matters.

38

Reynolds number Re = ρvD/η, with turbulence appearing above about 2,000-2,300 — reached in the ascending aorta at peak systole, at a stenosis, and downstream of a prosthetic heart valve, where it is audible as a murmur or bruit.

39

Poiseuille's law Q = ΔP·πr⁴/(8ηL) and the Bernoulli relation underpin the estimation of pressure gradients from Doppler velocities. • Wall shear stress is central to device and vascular design: low and oscillatory wall shear stress promotes atherosclerosis and thrombus formation (which is why plaques form at bifurcations and the carotid bulb), while excessively high shear damages red cells (haemolysis) and activates platelets — the fundamental design constraint for heart valves, blood pumps, ventricular assist devices, oxygenators and dialysers.