Human Structure and Function Full Notes PDF

Contents Foundations Osmosis and Diffusion............................................................................................................................................... 3 Physiology and Homeostasis.....................................................................................................................................4 Drugs......................................................................................................................................................................... 6 Embryology................................................................................................................................................................ 8 Membrane Potential.................................................................................................................................................12 Central Nervous System.......................................................................................................................................... 13 Peripheral Nervous System..................................................................................................................................... 16 Action Potential........................................................................................................................................................ 18 Drugs: Agonists........................................................................................................................................................20 Drugs: Antagonists...................................................................................................................................................21 Neuromuscular Neuromuscular Junction.......................................................................................................................................... 22 Sensory receptors....................................................................................................................................................24 Somatic Reflexes..................................................................................................................................................... 26 Excitation Coupling.................................................................................................................................................. 27 Force Relationship................................................................................................................................................... 30 Muscle Physiology................................................................................................................................................... 32 Autonomic Nervous System.....................................................................................................................................34 Autonomic Pharmacology........................................................................................................................................ 35 Musculoskeletal Foundations of Anatomy.......................................................................................................................................... 38 Muscular system & muscles.................................................................................................................................... 39 Skeletal system & bones..........................................................................................................................................42 Articular system & joints...........................................................................................................................................44 Vertebral Column & Back.........................................................................................................................................46 Upper Limbs.............................................................................................................................................................47 Lower Limbs.............................................................................................................................................................50 Cardiorespiratory Vascular system and vessels...................................................................................................................................54 The Heart................................................................................................................................................................. 58 Coronary and Great vessels.................................................................................................................................... 62 Cardiac Muscle Physiology......................................................................................................................................65 Blood Vessels.......................................................................................................................................................... 72 Baroreflex.................................................................................................................................................................77 Cardiovascular Pharmacology................................................................................................................................. 82 Gas Transport and Exchange.................................................................................................................................. 88 Thoracic Walls and Diaphragm................................................................................................................................ 92 Upper Respiratory Tract...........................................................................................................................................96 Lower Respiratory Tract...........................................................................................................................................98 1 Mechanics of Ventilation........................................................................................................................................ 101 Neural Control of Ventilation.................................................................................................................................. 103 Guts and Gonads Female Reproductive System................................................................................................................................105 Male Reproductive System.................................................................................................................................... 107 Reproductive Physiology....................................................................................................................................... 109 Abdominal Walls.....................................................................................................................................................119 Digestive Organs................................................................................................................................................... 123 Accessory Digestive Organs..................................................................................................................................125 Gastrointestinal Physiology....................................................................................................................................128 Urinary System...................................................................................................................................................... 136 Kidney Function & Filtration................................................................................................................................... 138 Renal Physiology................................................................................................................................................... 141 Therapeutics Drug absorption, distribution and elimination.........................................................................................................149 Acid-base regulation.............................................................................................................................................. 153 Toxicology, adverse effects & tolerability............................................................................................................... 157 Drug Discovery...................................................................................................................................................... 160 Drug development & Evaluation............................................................................................................................ 162 Drugs in Clinical Practice....................................................................................................................................... 164 Respiratory Therapeutics.......................................................................................................................................168 Gastrointestinal Therapeutics................................................................................................................................ 172 2 Osmosis and Diffusion Two fluid compartments in the body 1. Extracellular fluid; fluid outside the cell (ECF) Plasma: Fluid portion of the blood, restricted to the circulatory system, contains: dissolved proteins, and ions Interstitial Fluid: Fills the space between cells in the body, similar to plasma, very few dissolved proteins. Surrounds cells. 2. Intercellular fluid; fluid inside the cell (ICF) In the cytoplasm, very different to ECF Surrounds the cell Barriers Plasma: interstitial - capillary wall Interstitial: intracellular - cell membrane Intracellular contents - - high K+ and low Na+ Concentration gradient: Na+ wants to enter the cell & K+ wants to leave the cell Diffusion - Movement of particles dissolved in a solution to even the distribution of that particle Process where molecules move to even their concentration throughout a space Occurs when the net flow is from a region of high concentration to low concentration. Does not require extra energy; therefore is a passive process. Net movement of the substance will continue down its concentration gradient until it is distributed evenly in the space. Osmosis - Movement of water across a semipermeable membrane to even the concentration of dissolved substances on both sides ★ Diffusion cares about individual identity of the molecules, osmosis only cares about the number of molecules. Concentration describes the number of a particular molecule dissolved in a volume of solution (specific particle, molar M) Osmolarity describes the total number of dissolved particles in a volume of solution (total of particles, milliOsmolar mOsM) Tonicity describes the cell behaviour of non-penetrative solvents (can’t cross membrane) Isotonic - Balanced. Cells retain their normal size, no net movement. Hypertonic - Cells lose water and shrink in a solution of higher concentration (water leaves to make inside more concentrated) Hypotonic - Cells gain water and enlarge in a solution of lower concentration (water enters to make inside less concentrated) Diffusion across membranes Phospholipid bilayer regulates what enters and leaves the cell, and type of transport (active, facilitated diffusion, or diffusion) Easily diffuses: hydrophobic molecules, small, polar, uncharged molecules (water) Can not cross: large, uncharged, polar molecules and ions Substances carried in the blood require a transport protein. Fick’s law of diffusion determines how easily something can cross a barrier Factors that increase rate of diffusion High concentration gradient (Δ diffusion ∝ Δ concentration) High permeability (permeability ∝ lipid solubility/molecule size) Less distance to travel (Δ diffusion ∝ 1/Δ distance) Larger surface area (Δ diffusion ∝ Δ SA ) 3 Physiology and Homeostasis Homeostasis Maintenance of a relatively stable internal environment. Self-regulating. Disease occurs when oscillations go beyond optimal range. Negative feedback Closed loop, self-regulating. Always returns to homeostasis. Positive feedback Open loop, feedback amplification. Shifts back and forth between stages, e.g. childbirth contractions Negative feedback control system features 1. Variable being regulated - controlled condition 2. Sensor (or receptor) that can detect the controlled variable 3. Input system - can carry messages to the integrator (afferent) 4. Control centre (aka integrator) can compare actual value with intended value 5. Output system - carry message to response system (efferent) 6. Effector - the response system 7. Response e.g. blood glucose levels drop - Blood glucose monitor detects fall in glucose - Signals to the integrating centre via afferent pathway - Pancreas cells will release a hormone called glucagon - Hormone travels via efferent pathway to muscles to use stored glucose for ATP Positive feedback amplification Stimulus results in activation of a response Response acts as a stimulus to reinforce (amplification) - Myometric contraction - Blood clotting - Action potential - Endocrine control of ovulation Requires regulatory signals to shut off e.g childbirth - As the head pushes against the cervix, it stimulus more contractions - More contractions push the head further out - More pushing leads to more contractions 4 Control of homeostasis Neurotransmitters Chemical messengers that carry signals through neurons Synapse - the point at which two neurons meet Synaptic cleft - gap between neurons Hypothalamus Region of the brain that acts as the ‘integrator’ for many homeostatic reflexes Regulates the endocrine and autonomic nervous system Neural control of homeostasis Produces neurosecretory cells - Produce oxytocin (for birth and delivery) - Produce antidiuretic hormone called vasopressin (causes blood vessels to constrict, increasing pressure) - Releases tropic Posterior Pituitary gland Neurosecretory region Two neurosecretions; oxytocin and antidiuretic Anterior Pituitary gland Hormone secretion; releases tropic Region of hypothalamus makes constant with blood vessels, drains into anterior, releasing hormones going out to the rest of the body to release more hormones Neurosecretions of hypothalamus into the anterior pituitary RH - releasing hormone Stimulates release of tropic hormones from the anterior pituitary IF - inhibitory factor Inhibit release of tropic hormones from the anterior pituitary Tropic - A hormone that stimulates another gland to release hormones Basic regulatory patterns 1. Skeletal muscle movement 2. Antidiuretic hormone (vasopressin) 3. FSH- androgen binding protein 4. Thyroid hormone 5. FSH- oestrogen 6. Insulin 5 Drugs Drug - A medicine or other substance which has a physiological effect or a chemical substance which has a biological effect. - Drug class produces information on mechanism of action. Drug targets 4 regulatory proteins Receptors: receive and transduce responses to chemical mediators Ion channels: allow passage of ions across cell membranes when open; not a fixed number Enzymes: biological catalysts Carrier molecules: transport fixed number of substances across cell membrane Pharmacokinetics Rate and extent of movement of drugs into the body is affected by absorption and distribution. Rate and extent of movement of drugs out of the body is affected by metabolism and excretion. Signalling between cells Chemical signalling allows for communication between cells. Released molecules bind receptors on target cells Local mediators, neurotransmitters, hormones, growth factors, metabolites Bound receptors interact with effector/s which begin cellular response Enzymes, channels, transporters, transcription factors Drug molecules can disrupt or mimic cell communication Types of communication Endocrine Soluble chemical signals secreted from cells enter circulation and are transported to a distant location. Cells must express a receptor to receive a signal and elicit a cellular response; target cells. Paracrine Communication between nearby cells. Autocrine Cell signals to itself by receiving signals that bind to receptors expressed on its own surface. 6 Types of receptors Ligand-gated ion channels Open when a molecule binds to specific ligands. Allows movements of ions through the pore; chemical → electrical signal Is a receptor and effector, very rapid cellular response (milliseconds) G-protein coupled receptors Single polypeptides with 7 transmembrane domains Receptor activation elicits a conformational change and resulting interaction with a G - protein allows signals to be transduced from outside the cell to inside. Multi-step process, intermediate time for cellular response (seconds) Catalytic receptors Subunit comprises of - Extracellular ligand-binding domain - Transmembrane-spanning domain - Intracellular domain with intrinsic catalytic activity Binding of ligands to receptors leads to activation of downstream signaling pathways. Often involves changes in gene transcription and protein translation Found on cell surface; very accessible Long time for cellular response (hours) Nuclear receptors Located in the nucleus or cytoplasm Elicits effects after it has migrated into the nucleus following binding of ligands Can enhance or repress gene transcription. Long time for cellular response (hours) Receptors as amplifiers Second messengers able to amplify signals and direct signals to specific cellular locations Second messenger concentrations must therefore be tightly regulated Regulation is made possible as - Generation of second messenger occurs in response to a signal; allows it to be very rapid - Mechanisms exist in place to inactive second messengers 1. Single drug molecule binds to a G-protein coupled receptor 2. G-protein mediated actiation of a membrane bound enzyme 3. Subsequence generation of multiple second messengers 4. Each messenger can module the activity of downstream effectors 7 Embryology Fertilisation to end of 2nd week (conceptus), 3rd week - end of 8th week (embryo), 3rd month to birth (foetus) Stages 1. Ovulation - An oocyte exits the ovary into the oviduct 2. Fertilisation - The oocyte travels up the oviduct, and is penetrated by a sperm creating a zygote (fertilised egg) 3. Cleavage - Zygote undergoes numerous rounds of mitotic cell divisions 4. Morula - Solid ball of cells that form as a result of the mitotic division 5. Blastocyst - Morula enters the uterus and the cells drift apart producing a hollow ball of cells (blastocyst) 6. Implantation - Blastocyst attaches itself to the uterine lining, and inner mass begins to form primary germ layers Blastocyst two types of cells Outer epithelial layer (trophoblast); forms extraembryonic structures Inner cell mass Two germ layer stage Inner cell mass splits Cavities form Form embryonic disc Epiblast gives rise to embryo Hypoblast gives rise to extraembryonic structures Gastrulation formation of primitive streak On upper surface of bilaminar disc (epiblast), a line of thickened cells appear (primitive streak) Primitive streak invaginates to form primitive groove Cells of epiblast migrate medially into primitive groove First cells move into the hypoblast to form the embryonic endoderm. Later cells move between epiblast and endoderm, becoming embryonic mesoderm. Celle left in epiblast become embryonic ectoderm Three layer stage Raphe - Connective tissue that provides support to muscles meeting in the midline of the body. Node - Important for setting up left-right symmetry - Cilia within the node rotate creating leftward fluid flow. Situs Invertus - Organs are mirrored from normal position Formation of the notochord Cartilage-like transient structure Guides the folding of the embryo Cranial midline extension to form hollow tube Tube grows in length (cells added from primitive streak) Primitive streak regresses Mesodermal Formation of neural plate and neural tube Ectodermal cells above notochord thicken and differentiate Extension and folding of neural plate Convergence of neural folds Neural tube closure 8 Neural Plate Induced by notochord Cranial to primitive node Ectodermal cells differentiate into thick plate of pseudostratified, columnar neuroepithelial cells = neuroectoderm Neural tube Formation = neurulation; derived from ectoderm. Invagination of neural plate Develops into the spinal cord and brain (CNS). Neural crest cells give rise to: dorsal root ganglia, enteric ganglia, schwann cells, melanocytes Segmentation of neural tube Neural tube initially one layer thick and hollow Cranial end begins to swell and forms vesicles which give rise to brain Remainder of cranial cells give rise to spinal cord Body folding End of third week: embryo is flat, ovoid, trilaminar disc Fourth week: embryo grows rapidly, especially in length - Embryonic disc grows rapidly, yolk sac experiences almost no growth - Developing notochord, neural tube, and somites stiffen dorsal axis Growth of the neural tube drives embryonic folding Germ Layers Ectoderm outer layer Epidermis, sweat glands and hair cells & epithelial lining of mouth & anus Nervous system; nerves, spinal cord Mesoderm middle layer Paraxial mesoderm Forms somites which produce muscle, bones, and dermis Intermediate mesoderm Forms the urogenital system Kidneys, gonads, and respective duct systems Lateral mesoderm Divided into somatic and splanchnic mesoderm Bones, heart, vasculture, wall of gut. Mesoderm gives rise to all supporting tissue, dermis, muscle types, and blood vessels walls. Notochord. Endoderm Epithelial lining of digestive and respiratory tract (stomach and lung cells) Liver, pancreas, thymus, thyroid and parathyroid glands (in pharynx) Somitogenesis in paraxial mesoderm Formation of somites Somites - bilaterally paired blocks of paraxial mesoderm that form along the anterior-posterior axis of the developing embryo 9 Gut tube Lateral folding of the embryo completes the gut tube Mesoderm is recruited to gut wall Mesodermal layer of the gut tube from splanchnic mesoderm Somatic mesoderm lines body cavity Overview of germ layer fate Development of cardiovascular system Vasculogeneis - de novo assembly of blood vessels from mesodermally derived cells Angiogenesis - blood vessels forming from preexisting vasculature Development of stomach Distal part of foregut, around middle of fourth week Enlarges and broadens ventro-dorsally Dorsal part grows faster than ventral part: greater curvature of stomach 90 degree rotation clockwise whilst growing Ventral border (smaller curvature) moves to right, dorsal bored (greater curvature moves to left) Rotation superiorally bends duodenum into C-shape Development of other endodermal organs Endodermal thickening, cells proliferate to form bud Continuous lengthening and bifurcation/branching Development of lungs Ventral out-pocketing of endoderm= respiratory reticulum → will form trachea Grows ventro-caudally. (forward-down) #1 Bifurcation of lungs forms the bronchi. #2 Bifurcation forms secondary bronchial buds. 3 buds on the right, 2 on left. #3 Bifurcation forms tertiary bronchial buds and bronchopulmonary segments. 14 more branches until terminal bronchioles. 10 Gut and its derivatives Foregut Pharynx, oesophagus, stomach, proximal duodenum Thyroid, parathyroid, thymus, lungs, liver, gallbladder, pancreas Midgut Distal duodenum, half of colon Hindgut Other half of colon to anus Urinary bladder Pharyngeal arches Outer covering of ectoderm Mesenchymal core derived from mesoderm as well as neural crest cells Lines inside with endoderm Each arch contains: Central cartilaginous skeletal elements (Derived from neural crest) Striated muscle rudiment (Derived from head mesoderm) Arch-specific cranial nerve Aortic arch artery (endothelial cells derived from mesoderm) 11 Membrane Potential Active transport - direct expenditure of energy (via ATP hydrolysis) to pump Ca+ out of the cell against its concentration gradient. Facilitated diffusion - passive movement of ions down their concentration gradient Selective permeability of the membrane to K+ allows positive charge to leave the cell The K+ concentration gradient favours K+ efflux from the cell The efflux of K+ from the cell carries positive charge out of the cell, leaving anions behind (which can’t pass) Membrane potential - difference in charge across the cell membrane Resting membrane potential - change difference across the membrane when it is at rest. Only leak channels active. More permeable to K+, the more negative RMP will be because more K+ will leave the cell Action potential phases Depolarisation - Membrane potential increases to above 0mV. Repolarization - Membrane potential decreases back towards RMP Hyperpolarization - Membrane potential decreases to less than RMP (overshot); due to excess of K+ efflux Nernst equation predicts equilibrium potential of any ion Two sources of potential energy driving the movement of an ion; chemical concentration gradient, and electical charge Equilibrium potential - When the two driving forces (chemical and electrical) are balanced, and net ion movement is zero. Eₖ is typically more negative than the RMP. If the conductance across the membrane for K⁺ increases, K⁺ will leave the cell and the membrane will hyperpolarize. Increasing conductance for Na⁺ (potential needs to go up) will result in Na⁺ entering the cell, depolarizing the membrane. Driving force sum of all force on a particular ion pushing/pulling the movement of an ion ★ Driving force = membrane potential - nernst equation Na has greater driving force than K - Opening a Na+ selective ion channel will depolarise the membrane - Opening a K+ selective ion channel will hyperpolarise the membrane Monovalent cation channel - equally permeable to K+ and Na+ Channels Leak channel - a channel that is always open Voltage gated ion channel - An ion channel that opens or closes depending on the polarity of membrane potential. Ligand gated ion channel - Open or closed state depends on the presence or absence of a ligand (chemical) bound to receptor Mechano-gated ion channel - Mechanical stimulus opens or closes the ion channel. e.g. stretch, touch, baroreceptor At rest, the membrane is more permeable to K+, so the membrane potential is closer to that of K+. When Vm > Ek, K+ will flow out of the cell. When Vm A NA > A NA and A A >> NA Influence Direct innervation Direct innervation Direct & circulatory Circulating adrenaline Overall Stimulation Inhibition Stimulation Inhibition Effect 34 Autonomic Pharmacology Autonomic Nervous System Targeting the ANS Advantages Potential to pharmacologically alter a variety of tissue/organ functions; good way. Targeting the ANS has wide therapeutic opportunities Disadvantages Potential to pharmacologically alter a variety of tissue/organ functions; do harm. Targeting the ANS has great potential for adverse effects Responses occur when the ligand (neurotransmitter) binds to and activates its receptor. Cholinoceptors Nicotinic: ligand-gated ion channel, influx of Na+. Fast, enables ganglion transmission & skeleton muscle responses Muscarinic: G-protein coupled receptors, intermediate response time, postganglionic parasympathetic responses Adrenoreceptors α,β-adrenoceptors: GPCR, intermediate, postganglionic sympathetic responses. Modulating chemical transmission allows manipulation of autonomic & somatic tissue regulation. Steps in chemical transmission 1. Action potential propagation and depolarization of nerve terminal 2. Synthesis 3. Storage 4. Release 5. Receptor activation 6. Reuptake 7. Degradation Drugs affecting neurotransmitter release Ca2+ dependent vesicular exposure 1. Vesicle docks at active zone ACh filled synaptic vesicles have synaptobrevin (a SNARE protein) which forms a SNARE complex with target SNAREs (snap-25 & syntaxin). This brings vesicle close to plasma membrane. 2. Increase in Ca2+ sensed by synaptotagmin (protein) found on vesicle membrane 3. Ca2+ bound synaptotagmin triggers membrane fusion leading to neurotransmitter release 4. ACh binds to nicotinic receptors leading to muscle contraction Botulinum Toxin Heavy chain binds with high-affinity to specific receptors on the membrane of terminals containing ACh. Impacts cholinergic transmission. Causes light chain to cleave SNARE proteins → SNARE complex can not form → Inhibit release of Ach → neurotransmitter not released → muscle fibre paralysed. Botulinum Poisoning Caused by c.botulinum; anaerobic bacteria found in soil, plants and water - produce toxin under anaerobic conditions. Progressive motor paralysis (varying degree of muscle weakness) - Difficulty swallowing, facial weakness (droopy eyelids, hanging jaw), trouble talking, limb paralysis, may progress to respiratory paralysis Inhibition of parasympathetic-mediated effects - Dry mouth, dry eyes, urinary retention, constipation - Anti-SLUD (salivation, lacrimation, urination, defecation) 35 Transformed from poison to medicine Cosmetic use: paralyses superficial muscles that pucker the skin to smooth wrinkles (local injection) Clinical use: unwanted movement disorders, urinary incontinence associated with bladder overactivity, hyperhidrosis (excessive sweating) Drugs affecting neurotransmitter uptake Inactivation of sympathetic neurotransmission via reuptake Primary process: Neuronal uptake via high-affinity NA transporter (NET) Secondary process: Extranauronal uptake via low-affinity organic cation transporter (OCT3) - Following reuptake: NA is transported into vesicles via vesicular monoamine transporter (VMAT) for re-release If not transported, it is metabolised by monoamine oxidase (MAO) in nerve terminal Any NA taken up bt OCT3 also undergoes metabolism by COM in non-neuronal tissue. Uptake inhibitor - Cocaine 1. Cocaine inhibits NET (NA transporter) → inhibits reuptake of of noradrenaline into nerve terminal 2. Greater concentration of NA in junction and prolonged presence in junction 3. More noradrenaline to bind and activate post-junctional adrenoceptor → enhanced tissue response (sympathomimetic) Indirectly acting sympathomimetics (IAS) (mimic tissue responses of sympathetic activation indirectly) Structurally similar to NA 1. Transported into nerve terminal by NET 2. Transported into vesicles by VMAT in exchange for NA.--> NA displaced into cytosol. 3. High amount displaced cytosolic NA exits the nerve terminal via NET (Ca2+ independent) 4. NA activates post-junctional adrenoceptors thus IAS are sympathomimetic. 5. IAS an be metabolised by MAO in the cytosol e.g. pseudoephedrine Nasal decongestant. Constricts arteries in nasal mucosa with limited central effects. Inactivation of cholinergic neurotransmission via ACh metabolism → 1. Presynaptic terminal releases ACh 2. Release of ACh from synaptic vesicle binding to nicotinic receptors to elicit skeletal muscle contraction 3. ACh can be rapidly metabolised by AChE (acetylcholinesterase) → choline & acetic acid 4. Choline (precurses of ACh) can be taken back up into nerve terminal to make more ACh Drugs inhibit AChE AChE metabolises ACh Anticholinesterases or acetylcholinesterase inhibitors e.g. neostigmine for Myasthenia Gravis, or to reverse nondepolarizing skeletal muscle blockage Normal NMJ function 1. Arrival of single nerve impulse releases a package of ACh 2. ACh binds to and activates nAChRs (nicotinic receptors) to elicit end plate potential 3. Influx of sodium ions in skeletal muscle fibre → end plate potential → skeletal muscle contraction 4. ACh is rapidly hydrolysed by AChE which helps end tissue response. 36 Myasthenia Gravis 1. Auto-antibodies block and target nAChRs for degradation 2. Less nAChR available to bind to ACh 3. Most ACh released following arrival of impulse rapidly degrade before sufficient receptors are activated 4. Only a weak end plate is generated → doesn’t reach threshold 5. Muscle weakness Myasthenia Gravis: Treatment with Neostigmine Neostigmine (acetylcholinesterase inhibitor) 1. Neostigmine inhibits AChE which prevents ACh metabolism 2. Enables lateral diffusion of ACh to bind to unaffected nAChRs (not yet targeted for degradation of antibodies), and rebinding of ACh 3. Restores cholinergic transmission in NMJ (restore skeletal muscle contraction) leading to symptomatic improvement. Sympathetic nerve-mediated responses Numerous smooth muscles have different response to sympathetic activation (relatation, contraction, constriction etc) Due to differences adrenoceptors - Control different biochemical pathways, and hence different physiological responses. Therapeutic benefits of selectively targeting a receptor subtype - Elicit wanted responses and minimise adverse effects Cholinergenic receptors: Muscarinic Effects mediated by PNS: DUMBBELLS - defecation, urination, miosis, brachycardia, bronchoconstriction, emesis, lacrimation, salivation Atropine Competitive reversible muscarinic receptor antagonist Binds to the same sites as ACh on muscarinic receptors. Does not activate the receptor; it inhibits responses. - Uses: Reduce secretions during anaesthesia, and treats anticholinesterase poisoning. Cholinergic receptors: Nicotinic Ligand gated ion channels Two major subtypes N1: Neuromuscular junction N2: Autonomic ganglia Numerous functional receptor isoforms identified. Differences in subunit comparison can lead to differences in: Cation permeability Physiological function Pharmacological properties - D-tubocurarine - nAChR antagonist (NMJ) - Hexamethonium - nAChR antagonist (autonomic ganglia) d-Tubocurarine: Competitive reversible nicotinic receptor antagonist Located in NMJ but also autonomic gangle at higher concentrations Use: Neuromuscular blocking drug (muscle relaxant in anaesthesia - obsolete) Adverse effects: Hypotension due to ganglion-block. Replaced with drugs that are less effective at autonomic ganglia. E.g. pancuronium - Used as an arrow poison due to its ability to paralyse skeletal muscles by blocking the neuromuscular junction Can’t cross mucus membrane, humans can safely consume poisoned animals. 37 Foundations of Anatomy Cardinal planes and axes Coronal (frontal): divides anterior and posterior Sagittal (medial): divides left and right Transverse: divides upper and lower Comparison terms Superficial: nearer to surface Intermediate: between a superficial and deep structure Deep: furthest from the surface Hands: Palmar and dorsal (back); palmer posterior is anatomical position. Feet: Plantar and dorsal (superior) Movements Flexion: bending, or decreasing the angle between body parts or bones Extension: straightening, or increasing angle Abduction: moving away from the midline Adduction: moving towards the midline Medial rotation: rotation toward the midline Lateral rotation: rotation away from the midline Elevation: movement in a superior direction (up) Depression: movement in an inferior direction (down) Protrusion: movement anteriorly Retrusion: movement posteriorly Protraction: anterolateral movement of scapula Retraction: posterolateral movement of scapula Pronation: rotation of radius medially so that the palm faces posteriorly from anatomical position Supination: rotation of the radius laterally so the palm faces anteriorly. Dorsiflexion: flexion of the ankle joint, lifting the front of the foot and toes off the ground Plantarflexion: bending the foot and toes toward the ground (tippy toes) Eversion: movement of the sole of the foot away from the midline (abduction) Inversion: movement of the sole away from the midline (adduction) 38 Muscular system & muscles Muscle function Produce movement - Skeletal muscle for all locomotion and manipulation - Cardiac muscle pumps blood - Smooth muscle propels substances (food, water) Maintain posture and body position: Skeletal muscle maintain posture, counteract gravity Stabilise joints Generate heat: Muscles generate heat when they contract; thermogenesis. Properties of muscular tissue Electrical excitability: Ability of muscle to respond to stimulus to produce action potentials Contractibility: Contracts forcefully when stimulated by an action potential Extensibility: Ability to stretch without being damaged (determined by connective tissue in the muscle) Elasticity: Ability to return to original length and shape after contraction and extension Types of muscles Skeletal muscle Striated Voluntary Cardiac muscle Striated Visceral Smooth muscle Unstriated Increased use of muscle = minimal adipose tissue = healthy Structure of skeletal muscle Fibre: individual muscle cell wrapped in endomysium Fascicle: bundle of individual muscle fibres wrapped in perimysium Muscle: lots of fascicles wrapped in epimysium Patterns of fascicle arrangement Muscles have different shapes due to the arrangement of their fascicles Muscles generate power by contracting or shortening their fibres which generates tension Muscle fibres contract and lengthen only in the direction of their fascicles Different fascicle patterns Circular, Convergent, Parallel, Pennate Circular fascicle arrangement Fascicles arranged into concentric rings Muscles surrounding external body openings (sphincters) Opens/closes sphincters via contraction Convergent fascicle arrangement Broad origin, fascicles converge toward a single tendon Strongest contraction Triangular or fan shaped 39 Parallel fascicle arrangement Length of fascicles runs parallel to the long axis of muscle Greatest shortening during contraction Straplike (sartorius) or, Spindle shaped with an expanded belly (biceps) Pennate fascicle arrangement Short and attach obliquely Unipennate: fascicles insert only one side of the tendon Bipennate: fascicles insert onto the tendon from opposite sides Multipennate: fascicles insert onto the tendon from many directions Muscle attachment Most skeletal muscles span joints and attach to bones/structures in at least two places. Muscle contractions causes movement at the joint When skeletal muscle contracts, it moves the articulating bones: - One bone remains stationary, whilst the other bone is pulled toward the stationary bone - Insertion moves toward origin (distal to proximal) Muscle movement caused by exerting force on tendon Connective tissues associated with muscle Tendon: muscle belly to bone Aponeurosis: muscle to bone (broader, flatter, greater area than tendon) Raphe: muscle to muscle (line of fibrous tissue) Ligaments: bone to bone (composed of collagen fibres and blend with periosteum) Muscle fibres contract in response to innervation, and shorten only in the difection of their fasicle Isometric contraction: Length does not change. No movement. (plank) Concentric contraction: Muscle fibres shorten. Muscle force exceeds force of gravity. (rasing barbell) Eccentric contraction: Muscle lengthens. Gravity exceeds muscle force (lowering barbel) Arrangements of muscle permits them to work together or in opposition to produce movements Prime mover: main muscle responsible for producing a specific movement (concentric) - e.g. biceps brachii prime mover of elbow flexion Synergist: complement action of prime mover by adding extra force or removing unnecessary movement. - e.g. brachialis synergist of biceps in elbow flexion Antagonist: muscle that opposes action of another muscle (eccentric) - e.g. triceps brachii opposes biceps during elbow flexion Fixator: steadies proximal parts of a limb while movements occur in distal parts (isometric) - e.g. rotator cuff muscles stabilise shoulder during elbow flexion ★ The action of a muscle can be inferred by the position of the muscle relative to the joint it crosses. Above the knee, a muscle that crosses anteriorly produces flexion posteriorly produces extension on the lateral side produces abduction on the medial side produces adduction 40 Fascia wrap, package and insulate deep structures. Superficial fascia - loose subcutaneous tissue Deep fascia - thin, rough sheet made primarily of collagen fibres - Strong, inelastic, no fat, covers most of the body, not found where expansion is required Deep fascia structures Fascial septum: extension of dense connective tissue Retinaculum: thickening of deep fascia that holds down tendons Neurovascular supply One nerve, artery, and one or more veins serve each muscle. All enter or exit near centre of muscle. Every skeletal muscle fibre is supplied with a nerve ending that controls activity. Muscles have a rich blood supply. Lots of energy, oxygen, and nutrients required (delivered via arteries) Metabolic waste is produces (removed via veins) Receive blood supply via muscular branches from adjacent arteries; drained via veins (huge blood supply) Individual muscle fibres are in close contact with capillaries Major source artery and vein enter muscle belly via neurovascular hilum Motor nerves supplying skeletal muscle always enter the belly from a deep aspect. Skeletal muscle is voluntary. Brain sends electrical signals down to the spinal cord, through nerves that activate fibres and muscles contract. Motor unit - a motor nerve fibre and all of the muscle fibres it innervates. Motor neuron in ventral/anterior horn of spinal cord is stimulated by impulses down descending pathway All muscle fibres supplied by that neuron contract simultaneously 41 Skeletal system & bones Bone function Support Protection Movement: skeletal muscle attach to bone; contraction pulls on bone to produce movement Mineral homeostasis Blood cell production: Red bone marrow produces red blood cells, white cells, and platelets Triglyceride storage: Yellow bone marrow stores triglyceride in medullary cavity Axial skeleton consists of about 80 bones - (head, neck, trunk (ribs, vertebral column, sacrum) Appendicular skeleton consists of about 126 bones. Appendages (arms and legs)- limbs including pelvic and pectoral, clavicle, agnomical bone (hips) Bone is a form of connective tissue; contains extracellular matrix surrounding cell Contains organic compounds (collagen, water), and crystallised mineral salts (calcium phosphate, makes the bone opaque) - Deposited in collagen of extracellular matrix then hardens - calcification Bone anatomy Compact bone: Dense bone that forms outer shell. Composed of osteons. Spongy bone: Underneath the compact shell. Composed of lamellae, arranged into trabeculae. Periosteum: Dense layer of vascular connective tissue that surrounds bone (except at the surface of joints). Bone shapes Long bone: Bear a lot of weight Short bone: Wide and good for support (includes sesamoid) Flat bone: Flat, slightly served and good for protection Irregular bone: Complicated shapes. Long bone anatomy Diaphysis: forms the long axis of bone Epiphysis: proximal and distal ends Metaphysis: between epiphysis & diaphysis. Contains epiphyseal growth plate. Medullary cavity: Hollow space within diaphysis. Filled with yellow (fg at) marrow + blood vessels. Lined by endosteum. Articular cartilage (hyalin cartilage): covers the joint surface. Endosteum: thin membrane, lines medullary cavity, internal bone surfaces, trabeculae, lines canals of compact bone Vascular supply of bone Bones are vascular and non innervated. Periosteal arteries: supply periosteum and outer compact bone. Enter through small canals. Large nutrient artery: enters via nutrient foramen at centre of diaphysis through compact bone. Enters medullary cavity, courses toward epiphyses. Divides into medullary branches. - Ends of long bone supplied by epiphyseal and metaphyseal arteries. Periosteum nerves supply the periosteum. Carry small pain fibres which makes it sensitive to tearing. Bones have sparse nerve supply, broken bones don’t hurt, the periosteum does. 42 Cell types Osteoblasts: bone building cells (bone deposit) Synthesis and secrete collagen fibres, organic components to build the extracellular matrix of bone. Initiate calcification Osteoclasts: break down bone ECM (bone resorption) Releases lysosomal enzymes and acids to digest proteins and mineral components of the extracellular matrix (ECM). Bone formation (ossification) All bones are derived from mesenchyme (embryonic connective tissue) by one of 2 processes. During fetal development. 1. Intramembranous ossification: directly from mesenchyme Mesenchymal models of bone form during embryonic period. Simple process. 2. Endochondral ossification: from cartilage derived from mesenchyme Cartilage models of bones form from mesenchyme during foetal period, bone replaces cartilage Intramembranous ossification 1. development of ossification centre. Cells differentiate. 2. Calcification occurs once ECM surrounds the cell 3. Formation of trabeculae; ECM develops into spongy bone 4. Development of periosteum Flat bones of skull, facial bones, mandible, medial part of clavicle, form via intramembranous ossification. Endochondral ossification 1. Development of cartilage model 2. Cartilage model grows 3. Development of primary ossification centre in diaphysis 4. Development of medullary cavity from ossification centre 5. Development of secondary ossification centre in epiphysis 6. Formation of cartilage and epiphyseal plate Bone growth occurs in length and diameter until adolescence. Then only in diameter. Epiphyseal cartilage → epiphyseal plate. Height growth stops once epiphysis closes. Longitudinal bone growth 1. Interstitial growth of cartilage on the epiphyseal side of the epiphyseal plate 2. Replacement of cartilage on the diaphyseal side with bone via endochondral ossification Appositional bone growth Growth in width. New bone deposited on outer surface, old bone inside is destroyed. Medullary cavity enlarges as bone increases in thickness Epiphyseal plate: layer of hyland cartilage in the metaphysis Chondrocytes proliferate on epiphyseal side. New chondrocytes replace older ones which are destroyed by calcification. Epiphyseal plate → epiphyseal line. Bone remodelling - combination of bone deposit (by osteoblasts), and bone resorption (by osteoclasts). Factors: vitamins and minerals, exercise, hormones. Females undergo increased bone loss due to menopause. Bone markings types Sites of muscle and ligament attachment Tuberosity, crest, trochanter, line, tubercle, epicondyle, spine, process Projections that help to form joints; Head, facet, condyle, ramus Depressions and openings for passage of nerves and vessels; Groove, fissure, foramen, notch, meatus, sinus, fossa 43 Articular system & joints Joint is a point of articulation between two bones. Classified based on: Presence or absence of space between articulating bones (i.e. synovial cavity) Type of connective tissue that binds bones together (i.e. cartilage) Cartilage is a flexible connective tissue, good for flexibility. Nourished via diffusion, no blood vessels or nerves. Consists of a dense network of collagen and elastin fibres Types of cartilage Hyaline: Most common type, covers bony articular surfaces (epiphyseal). Found in nose, larynx, trachea bronci Elastic: Flexible, contains a bundle of elastic fibres. Found in external eat, epiglottis. Fibrocartilage: Forms specialised joints. Strongest cartilage. Fibrous tissue + hyalin cartilage, most collagen fibres. Found in anterior hip joint. Types of joints Synovial (moveable) Bones united by a joint/articular cavity. Fibrous (solid, minimal movement) Bones united by fibrous tissue Degree of movement depends on length of fibres Cartilaginous (solic, menial movement) Provide strength and shock absorption Fibrous joints Solid. No joint cavity, held together by a dense irregular connective tissue Sutures: Thin layer of connective tissue called a sutural ligament in skull Gomphosis: Short collagen fibres running between root of tooth and bony socket. Periodontal ligament. Syndesmosis: Occurs where two adjacent bones are linked by a ligament. Cartilaginous joints Immovable. No joint cavity, joined by hyalin or fibrocartilage. Synchondroses: Bar or plate of hyalin cartilage between two ossification centres of a developing bone (growth plate) Symphyses: Fibrocartilage connecting two separate bones. Permits limited movement. Synovial joints Plane joint Allow sliding or gliding movement when one bone moves across the surface of another Nonaxial Hinge joint Concave surface of one bone wraps around the convex surface of another Uniaxial Flexion/extension Pivot joint Rotation along its longitudinal axis Uniaxial Condylar joint Convex oval projection of one bone fits oval depression of another Biaxial Flexion, extension, adduction, abduction 44 Saddle joint Biaxial. Allows more movement than condylar joint. Biaxial Flexion, extension, adduction, abduction Ball-and-socket joint Allows movement around all 3 anatomical axes; multiaxial Flexion, extension, adduction, abduction, circumduction, rotation Features of synovial joints Articular cartilage Hyalin cartilage covers articulating surfaces of bones - Differs to synchondrosis joints as in that case cartilage joints to the bone. By coating it, maximal movement is enabled. Joint capsule Synovial cavity filled with fluid. Surrounded by 2 layered structure. Inner synovial membrane: highly vascular, secretes synovial fluid Outer fibrous membrane: dense connective tissue, attaches to periosteum (continuation) Synovial membrane: Inner layer of double layer articular capsule. Connective tissue, lots of elastic fibres. - Secretes synovial fluid; removes friction at joint, and is shock absorber. Supplies O2, removes waste. Fibrous capsule: Encloses the synovial joint. Structures beyond this are intracapsular. - High amount of tensile strength, lots of movement. Dense connective tissue made of collagen fibres. Accessory structures Articular discs and menisci intracapsular. Made of fibrocartilage and connective tissue. Divides synovial cavity into two. Stabilises joint, and aids shock absorption. Labrum extracapsular Fibrocartilage lip that extends from the edge of the joint socket. Depends the socket, increases contact surface area. Fat pads intracapsular, extrasynovial. Act as space fillers, helps spread synovial fluid. Bursae and tendon sheaths extracapsular Flattened fibrous sacs lined with synovial fluid, used as a lubricant to reduce friction. Factors that affect movement of synovial joints - How well the bones fit together. How strong and tight the joint is. Additional ligaments. Muscles that wrap around the joint. Joint Mobility Range of motion (ROM): the range, measured in degrees of a circle (360) through which the bones of a joint can be moved. 6 factors Structure/ shape of articulating bones Strength and tension of joint ligaments Arrangement and tension of muscles (Flexed thigh restricts hip flexion. Flexed knee increases hip flexion) Contact of soft parts (ROM restricted when skin presses against skin) Hormones Disuse 45 Vertebral Column & Back Function of vertebral column Structure, Movement, Protection First secondary curvature - Cervical Second secondary curvature - Lumbar Accentuated primary curvature = kyphotic Accentuated secondary curvature = lordotic Vertebra Intervertebral contents Spinal nerve roots Dorsal root ganglia Vessels Intervertebral Joints discs Annulus fibrosus Attaches to epiphyseal ring. Keeps vertebrae together. Concentric lamellae of collagen. Permits multiaxial movement and resists excessive rotation. Nucleus Pulposus: Surrounded by annulus fibrosis. Keeps vertebrae apart. Absorb shock. Deforms. Zygapophyseal Joints: Plane synovial joints formed between superior and inferior facets of vertebral bones. Major Ligaments Ligaments allow extra stretch Posterior longitudinal Anterior longitudinal Interspinous Supraspinous Ligamentum flavum Muscles of the back Extrinsic - primarily attach to upper limb. Intrinsic - primarily attach to and act on the back Erector spinae - primary movers Concentrically extend the trunk Eccentrically control trunk flexion 46 Upper Limbs Bones & Joints Upper limb - Attaches to anterior aspect of axial skeleton Shoulder Girdle (clavicle & scapula) Clavicle Provides only upper limb articulation between appendicular & axial skeleton Sternum and acromial ends Scapula Clavicular Joints - sternoclavicular & acromioclavicular Sternoclavicular Saddle joint Intra Articular disc Strong capsule Acromioclavicular Plane joint Strong coracoclavicular ligament, weak capsule. Humerus Ulna & Radius Elbow Joint Hinge joint Glenohumeral Joint Strong collateral ligament support Ball and socket joint Humero-ulnar contact Large humeral head + shallow glenoid fossa Supportive features Specialised fibrocartilage: glenoid labrum = ‘incongruent Muscular: rotator cuff Ligament: glenohumeral & coracohumeral Proximal & Distal radio-ulnar joints Bone groups of the wrist & hand Proximal - Pivot joint Sesamoid bones - metacarpophalangeal Radial head to radial notch on ulna Distal - Pivot joint Ular head to ulnar notch on radius Radiocarpal joints Condyloid/Ellipsoid joint Ulnar-carpel contact Joints of the hand Joints of the fingers Intercarpal joints Metacarpophalangeal joint - condyloid Caropmetacarpal joints Interphalangeal joint - hinge 1st joint - saddle (thumb) 2-5th joint - plane Opponens pollicis (thumb muscle) 47 Upper Limbs Muscles, vessels, and nerves Axio-appendicular muscles ← Anterior View Pectoralis Major Attaches to humerus Movement & internal rotation Pectoralis minor Attaches to coracoid process Helps tilt scapula over thoracic case Secondary muscles for respiration Scapulohumeral muscles ‘Rotator cuff’ muscles Supraspinatus: superior to spine Infraspinatus: inferior to spine; traverse over back Teres Minor: lateral border; traverse over back Subscapularis: anterior Collective function: blend with joint capsule & compress humeral head into glenoid fossa. Major movements Abduction (supraspinatus) External Rotation (infraspinatus and teres minor) Internal Rotation (subscapularis) Deltoid & Teres Major Attach more distally on the humerus than rotator cuff Deltoid Prime mover Produces shoulder flexion, abduction, and extension Fan from humerus to scapula and clavicle Teres Major Attaches more anteriorly to humerus (from superior back) Internal rotation at shoulder Upper limb compartments & deep fascia Muscles are separated into compartments by intermuscular septa Deep fascia can be specialised Arm Muscles Anterior Compartment Biceps brachii (crosses elbow; flexor) Coracobrachialis Bracialis (crosses elbow) All cross over in the anterior aspect of at least one joint and produce flexion) Pronation muscles Pronator teres Arm Muscles Posterior Compartment Pronator quadratus Triceps Brachii (Extensor) Flexor carpi radialis All cross over at least one joint Supination muscles to attach onto olecranon process Supinator and produce extension. Biceps brachii Long head produces extension. 48 Forearm muscles Anterior Compartment Attach to carpal/metacarpal = wrist flexor Attach to digits = finger flexor Distal attachment to radius = pronator Finger flexion: caused by muscles in anterior forearm, and palm Forearm muscles Posterior Compartment Attaches to caral/metacarpal = wrist extensor Attaches to digits = finger extensor Finger extension: Caused by muscles in posterior forearm, and dorsum of hand Lateral epicondyle of humerus provides attachment for multiple superficial muscles Hand Musculature Thenar - radial side of hand; thumb muscle Hypothenar - ulnar side; opponens digiti minimi Interosseous - between the metacarpals Brachial Plexus Organisation Complex intertwining of axons and sensory supply to distinct regions of upper limb Spinal roots: C5, C6, C7, C8, T1. Anterior Nerves Posterior Nerves Musculocutaneous Nerve Continuation of the lateral cord Anterior compartment of the arm Axillary nerve Lateral cutaneous Immediately exits out of axilla (armpit) Wraps humerus to supply deltoid & teres minor Median nerve superior lateral cutaneous Medial & lateral cord Major supply for anterior forearm Radial nerve Minor supply of hand musculature Largest branch of posterior cord Anterior interosseous nerve arises Passes anteriorly over lateral epicondyle Long posterior journey Ulnar nerve Significant supply to posterior upper limb Continuation of medial cord Arm & forearm Posterior to medial epicondyle Arises from all 3 posterior trunks Major supply of hand musculature Most cutaneous innervation Minor supply for the anterior forearm Passes superficial to metacarpal Major upper limb arteries Transverse over flexor side of joints. Anastomoses at joints. Brachial artery - occluded during blood pressure reading Ulnar artery - Larger branch. Principal supply for upper limb Radial artery anastomoses with ulnar artery via palmar arch. Palpable. Superficial Venous and Lymphatic network Superficial veins Highly variable, commonly visible Begin on posterior hand as ‘dorsal venous arch’ Easily accessible Lymphatic vessels Follow superior veins Flow into ancillary lymph nodes Deep Venous pathway Deep veins accompany major arteries Two veins present on either side of the artery. 49 Lower Limbs Bones & Joints Sacrum articulates to pelvic bone Lower Limb Significant weight bearing Bony framework position changes vital for upright posture and gait Lateral shift of ala of the ilium Line of gravity: behind hip joint, in front of knee, way in front of ankle Pelvic Girdle Interface between axial skeleton and lower limb Ring structure permits force transfer and protection of pelvic contents ‘Hemipelvis’ formed by fusion of three bones Female pelvis is less vertical, larger, weaker, wider. Ala means ‘wing’ and is the large fanned superior component of the ilium bone. Sacrospinous ligament: splits sciatic foramen into greater and lesser. Pelvic Girdle Joints Sacroiliac joint (Sacrum-iliac) Synovial joint Significant ligamentous support for weight bearing Sacroiliac ligaments - Sacrotuberous and sacrospinous Pubic symphysis (pelvic bones) Illium, ischium, and pubic articulate with femur. Secondary cartilaginous joint (symphysis) Direct articulation of pubic bones anteriorly Femur Largest bone in the body Hip joint Ball and socket joint Large femoral head + relatively deep acetabulum = congruent (deeper than shoulder socket) Least stable during full flexion Supportive features Specialised fibrocartilage: Acetabular labrum Strong fibrous capsule Ligament: iliofemoral, pubofemoral & ischiofemoral - All blend into fibrous capsule. 50 Tibia and Fibula Tibia is larger; the weight bearing bone. More medial. With significant articular surfaces at the tibial plateau and trochlear notch Knee Joint 2 synovial joints within one capsule Patellofemoral (femur to patella) Tibiofemoral (femur to tibia) Modified hinge joint Allows flexion, extension, rotation. Medial & lateral meniscus improves contact, absorbs shock, spread synovial fluid. Strong ligamentous support but highly susceptible to damage. MCL, LCL, ACL, PCl ligaments. Cruciate ligaments (ACL + PCL) ACL more prone to damage. Collateral ligament (LCL + MCL) Medial resists valgus, lateral resits varus force. Medial more prone to damage due to attachments. Tibiofibular Joints Superior Plane joint Inferior Fibrous joint (syndesmosis) Prevents tibia and fibula from separating. Good stability + low loading → dislocation rare Talocrural Joints (talus to leg) Hinge joint (complicated) Dorsiflexion & plantarflexion Trochlea of the talus is wider and more anteriorly. This contributes to increased stability when the ankle is dorsiflexed. Bones of the foot Short (tarsals) Long (metatarsal, phalanges) Sesamoid bones Joints of the foot Intertarsal Tarsometatarsal Metatarsophalangeal Interphalangeal 1st metatarsophalangeal joint (toe) vital in creating efficient loading through the lower limb in gait. Important movement of subtalar and midtarsal regions. Inversion: rolling foot medially Eversion: rolling foot laterally. 51 Lower Limbs Muscles, nerves, and vessels Pelvic girdle Anterior Iliacus + psoas major = ‘iliopsoas’ Strong hip flexor Piriformis muscle Gluteal region Lateral rotation, abduction Posterior Gluteus maximus - hip extensor Gluteus medium & minimus - hip abductors Thigh Muscles Anterior compartment Sartorius (hip flexion) Quadriceps femoris Vastus medialis, vastus lateralis, vastus intermedius, rectus femoris Quadriceps femoris cross the anterior knee via soft tissue structures and the patella (knee extension) Thigh Muscles Posterior compartment Hamstrings Semitendinosus, Semimembranosus, Biceps femoris (long and short heads) Bicep does flexion only. Cross the posterior aspect of the hip and knee joints → hip extension and knee flexion. Contribute to knee rotation. Leg Muscles Anterior Compartment Intrinsic foot muscles Dorsiflexors & Toe extensors ← Plantar view Lateral Compartment 3 major groups Eversion & Weak plantiflexer Hallucis muscles - 1st digit (big toe) Posterior Compartment Digiti minimi muscles (5th digit (small toe) Superficial Central muscles - varied attachment Strong plantar flexors Deep Dorsal view → Plantar Flexors & toe flexors Ankle tendon: Fibularis brevis & fibularis longus. Crosses the ankle posterior to lateral malleolus. 52 Fibularis Tertius tendon crosses ankle posterior to lateral malleolus and cross planter to surface of foot to attach to 1st metatarsal. Lower limb neural overview Lumbar and lumbosacral plexus supply the lower limb in addition to components of the pelvis and lower abdomen Anterior Femoral nerve Saphenous nerve Receives input from L2-L4 anterior rami Travels lateral to the psoas major Leaves the abdomen by travelling deep to inguinal ligament with major femoral vessels Innervates anterior thigh Obturator nerve Receives input from L2-L4 anterior rami Travels medial to the psoas major Leaves the pelvis via the obturator canal Splits into two branches; supplies medial thigh Sciatic nerve Main nerve Supplies all leg and foot muscles. Receives input from L4-S3 anterior rami Forms within the pelvis, leaves via greater sciatic foramen - Inferior to the piriformis Two nerves in a common sheath; tibial, common fibular. Common Fibular nerve Travels posterior to knee joint Wraps around the fibular neck and splits into two Superficial fibular nerve (supplies lateral compartment) Deep fibular nerve (supplies anterior compartment & dorsal foot) Supplies lateral & anterior leg + dorsal foot musculature Tibial nerve Travels posterior to knee joint Supplies posterior leg compartment Supplies majority of foot musculature (plantar) Travels through tarsal tunnel to enter foot. Major lower limb arteries Abdominal branching gives ride to external iliac artery External iliac artery → femoral artery when passes deep to inguinal ligament Femoral artery → popliteal artery Femoral artery passes through adductor hiatus (anterior → posterior) to enter posterior thigh. Femoral artery - initial incision and entry for embalming donors. Major lower limb veins Muscular venous pump is important for venous return Venous valves permit a unidirectional flow Lower limb lymphatics Drainage courses Planter digital vein → posterior tibial vein → popliteal vein → femoral vein Dorsal venous arch → great saphenous vein → femoral vein Drainage follows the path of the superficial veins of the lower limb Drainage progresses for both limbs to enter the cisterna chyli and thoracic duct. Superficial veins on left, deep veins on the right → 53 Vascular system and vessels Circulatory System Cardiovascular system Pulmonary circulation (O2 poor blood to lungs for oxygenation) - From pulmonary arteries System Circulation (O2 rich blood to the body for circulation) - From systemic arteries Lymphatic system Fluid in interstitial spaces Drains surplus tissue fluid, plasma proteins, removal of debris from cellular decomposition, infection Lymph plexuses; dense concentrations of lymph nodes, vessels, and extra tissues) Development of vascular and lymph system Vascular system is mesoderm derives; only present in mesoderm Avascular and non-lymph structures: Epidermis (ectoderm); surface epithelium (endoderm); articular cartilage (exception-mesoderm derived) Types of blood vessels 3 types of blood vessels: arteries, veins, capillaries All blood vessels have 3 layers (tunis) surrounding the (lumen) Final distributing vessel arterioles, deliver O2 rich blood to capillaries Arteries Oxygen-rich blood away from the heart, excluding blood leaving right ventricle which goes to lungs to be oxygenated. Blood under high pressure leaves the heart via arteries High calibre vessels → low → Capillary bed → veins Thicker tunic, smaller lumens Greater smooth muscle composition than veins Veins Deoxygenated blood back to the heart Thinner tunic, larger lumen; carries more blood than arteries (bigger) Capillies Capillary bed; nutrient and gas exchange takes place Tunics of blood vessels Tunica intima Innermost lining, flattened epithelial cells supported by delicate connective tissue Capillaries have only thus tunic basement membrane Tunica media Middle layer, mainly smooth muscle Most variable - thickness relative lumen differentiates arteries, veins, lymphatic ducts Tunia adventitia Outermost connective tissue layer of the sheath Arteries Clinical importance Arterial Bleeding - Blood flow in elastic and muscular arteries is pulsatile and at high pressure. - Reflects systole and diastole; ventricle contraction and relaxation - Blood tends to spurt and will be pulsatile blood flow when laceration to arterial vessels. Venus bleeding - Continuous low-pressure flow from capillaries, thin-walled veins. 54 - Veins have larger lumen, less elasticity and lower amounts of smooth muscle, largely held open by volume of blood. - Laceration to vein will be low pressure, and continuous seeping. Anastomoses - Links between arteries or between arterioles. - Provides potential detours for blood flow (collateral flow) if the usual pathway is obstructed. By joint position, pathology, or surgical ligation - Adjacent arteries tend to anastomose, and occur around joints, are significant only in muscle belly that crosses joint End arteries - Do not link with other arteries; no anastomose. Is not a ‘dead end’ - still branches into capillary beds drained by veins Blood passes through arteries of larger to smaller calibre. Types of arteries Large elastic arteries (conducting) Many elastic layers, resulting in the smooth flow of blood Near the heart, aorta and its major branches Medium muscular arteries (distributing) Circular smooth muscle fibres, capable of vasoconstriction + blood flow regulation Majority of named arteries Smooth muscle (autonomic) can contract vessels to reduce blood flow. Small arteries and arterioles Narrow lumina, thick smooth muscle walls Flow into capillary beds, tonus regulated arterial pressure in vascular system Can regulate blood flow and arterial pressure via vasoconstriction and vasodilation Heart pumps blood out at a high velocity and pressure. Elasticity in the large layers compensate for the spurting high velocity and smooths it out creating a continuous blood flow, rather than it being start and stop like heart beats. Principles of arteries of the limbs 1. Single stem artery (brachiocephalic) 2. Changes name according to the region it traverses 3. Travels on the flexor aspect of joints 4. Where it crosses a hinge joint artery will anastomose to avoid compression 5. Terminal branches are generated as the artery crosses the middle joint Upper limb: aorta → brachiocephalic → subclavian → axillary → brachial → radial & ulna. Veins More abundant than arteries; typically 80% of blood occupies veins Walls are thinner, but with a diameter larger than the corresponding artery (Large capacity for expansion) Usually depicted as a single vessel, but are typically double or multiple Deep arteries accompanies by venae comitantes Travel smallest to largest calibre; deep to proximal (opposite of arteries) Vascular sheath - a covering made of connective tissue contains the entire assembly of arteries and veins. 55 Types of veins Venules + small veins Venules are smallest drain capillary beds, are unnamed Small veins unite to form venous plexuses, are unnamed Small amount of smooth muscle and no elasticity Medium veins Drain venous plexuses, accompany medium arteries Often named according to artery then company Contain valves where blood flow opposed gravity Large veins Wide bundles of longitudinal smooth muscle Well-developed tunica adventitia Same tissue makeup as medium but more collagen making up adventitia, no elastic tissue, little endothelium lining lumen. Valves in veins Folds of endothelium lining veins, usually a pair of cusps Enforce one way blood flow from distal to proximal; prevent backflow of blood due to gravity. Often located distal to entry of tributary Principles of veins of the limbs 1. Superficial system of veins drains skin and superficial fascia 2. Deep system of veins drains deeper structures 3. Paired venae comitantes distally, single vessels proximally accompanying arteries 4. A set of communicating veins connects superficial and deep vein - Superficial veins outside of deep fascia, communicating veins connects through fascial layers to the deeper venus structures Capillaries Simple endothelial tubes connecting arterial and venous sides of circulation Allow exchange of materials with interstitial and extracellular fluid Arranged in beds that connect arterioles and venules Many beds according to organs and body regions Neurovascular supply Vascular smooth muscle has tone (continuous partial contraction) Modulated by visceral motor nerves - vasomotor nerves from neighbouring peripheral nerves Almost exclusively part of sympathetic nervous system Venous return flow Vascular venous pumps Venous flow returning to atria due to blood pressure, contraction of skeletal muscle, respiratory oscillation of intrathoracic pressure Vascular venous pumps result of arrangement of venae comitantes 56 Wrapped with connective tissue which resist expansion, arterial pulsation compresses blood in veins, valves direct flow proximally Musculovenous pump Main method of venous return from limbs Expansion of contracting muscles limited by fascia Muscles contraction ‘milks’ blood superiorly, squishes the blood upwards and valves prevent backflow Thoracic venous pump Double pump mechanism linked to respiration Descent of diaphragm Inspiration - diaphragm descends, IVC shortens and empties and SVC lengthens and fills Expiration diaphragm ascends, SVC shortens and empties, IVS lengthens and fills. Lymph system Runs parallel to the venous system, have valves, thinner walls, are more numerous Widely distributed, clears interstitial spaces of surplus fluid, leaked plasma proteins, and cellular debris + returns lymphocytes from lymph organs to blood Comprised of lymphatic plexuses (capillaries), vessels, major trunks (ie. thoracic duct), lymph nodes, and lymphoid organs. Organisation of the lymphatic vascular system Superficial (located under epithelium) and deep (in reticular layer of dermis) lymph capillaries Lymph capillaries drain into lymphatics - Larger tributaries with valves, one-way flow into venous system Superficial → deep nodes before emptying into venous system Lymphatic vessels Like blood vessels have 3 tunis Thinner walled than veins Lymph drainage facilitated by smooth muscle contractile waves Lymph nodes Superficial and deep lymph vessels traverse multiple lymph nodes Act as filters to trap particular in lymph and defend against foreign antigens Flow through nodes is slow, vulnerable to secondary tumours Become enlarges and tender when draining areas of infection Clusters of lymph nodes in sites of high risk for pathogen entry: surface, digestive and respiratory system Lymphatic trunks and ducts Lymph vessels become larger as they merge, large lymph vessels enter lymphatic trunks - Trunks unite to form right lymphatic duct or thoracic duct Ducts drain into the venous system at the neck; where internal jugular joins subclavian v Lymph from right head and neck, right side of upper limb, right side of thorax, right side of upper abdo drain into veins on right From all other regions drain into veins on left side Order of drainage - Superficial lymphatic capillaries → superficial lymph nodes → lymph vessels → deep lymph nodes → deep lymph vessels → lymphatic trunks. 57 The Heart Internal body cavities Closed to the outside, provide protection to the organs within them Separated from one another by bones, muscles, ligaments, and other structures Subdivided into several cavities: - Cerebral, Vertebral, Thoracic, Abdominopelvic Thoracic cavities Formed by ribs, muscles of chest, sternum & thoracic vertebral column Pleural cavity: Between layers of pleura around a lung Pericardial cavity: Between layers of pericardium around the heart Mediastinum: Central portion; contains heart, thymus, oesophagus, trachea + great vessels Pleural and pericardial cavities Lungs + heart covered by thin double-layered serous membrane Parietal serosa lines cavity walls Visceral serosa covers organs (deep) - Lubricating serous fluid between layers of serous membrane Mediastinum - Centrally located region extending from sternum to vertebral column, from 1st rib to diaphragm and between the lungs anteriorly. Extends obliquely from 12-14cm from the second rib to the 5th intercostal space Rests on the superior surface of the diaphragm Anterior to the vertebral column and posterior to sternum 2/3 lies left of the midsternal line, apex projects to the left Lungs flank heart laterally and partially obscure it Coverings of the Heart - Heart is enclosed in the pericardium; double-walled sac Outer layer Superficial part of the sac is fibrous pericardium Anchors it to surrounding structure (base attached to the central tendon of the diaphragm) Prevents overfilling of the heart with blood Inner layer Deep to fibrous pericardium is serious pericardium Thin, slippery two-layer membrane forming a closed sac around heart Parietal layer: Lines the inner surface of the fibrous pericardium Visceral layer: Adheres to the surface of the heart - Joints at the roots of great vessels. Pericardial cavity Space between parietal and visceral layers Filled with serious fluid Allows uninhibited movement of the heart 58 Orientation of the Heart Anterior surface; sternocostal surface Diaphragmatic surface; interior surface Base; posterior surface Left and right; pulmonary surfaces Anterior Surface Right ventricle Right atrium Left ventricle Posterior Surface ‘Base of the heart’ Left atrium Left ventricle Proximal components of great veins Fixed to the thoracic wall at the level of T5 to T8 Esophagus lies immediately posterior to the base. The Valves Cusps of fibrous tissue enforce one-way traffic of blood through heart. Atrioventricular valves: Separate the atria and the ventricles Prevent backflow into the atria when the ventricles contract Tricuspid & Mitral - Tricuspid; Separates the RA from RV (3 cusps) - Mitral; Separates the LA from LV (2 cusps) Semilunar valves: Between the great vessels and the ventricles Prevent backflow into the ventricles Aortic & Pulmonary - Aortic; separates LV from aorta (3 cusps) - Pulmonary; separates RV from pulmonary trunk (3 cusps) Atria and Auricles Anterior surface and each atrium has an auricle Increases capacity of each atrium to hold a greater volume of blood Little flaps upwards Right Heart Right Atrium Blood enters via three veins Superior vena cava (from regions superior to diaphragm) Inferior vena cava (inferior to diaphragm) Coronary sinus (blood from myocardium) - Smooth posterior - Anterior has ridges of muscles called pectinate muscles Left and right atria are separated by interatrial septum - Septum features fossa ovalis 59 Right Ventricle To the left of the right atria, forms the diaphragmatic surface Pumps blood into pulmonary trunk - To lungs for oxygenation Internal walls of ventricle marked by trabeculae carneae - Bulges on internal wall contribute to the papillary muscles Papillary muscles - Anterior, posterior, septal - Play a role in valve function Chordae tendineae - Chords of tendons attaching the papillary muscle to tricuspid valve Tricuspid Valve Located between the right atrium and right ventricle - Closes the right atrioventricular orifice Attached to the internal wall of the right ventricle by the chordae tendineae Contraction of papillary muscle anchors valve & prevents backflow in atrium during ventricular contraction (systole) Pulmonary Valve Fill the orifice between the right ventricle and the pulmonary trunk Three semilunar cusps with free edges - Free edges project into the pulmonary trunk - Forced open by contraction of ventricle, blood flow into pulmonary trunk - Backflow of blood after cessation of ventricular contraction fills the sinuses of valves & forces them closed Left Heart Left Atrium Forms the majority of the base/posterior surface of the heart Blood enters via four pulmonary veins - 2x left pulmonary veins - 2x right pulmonary veins Internal septum has fossa ovalis - Oval depression in the interatrial septum - Marks spot where an opening (foramen ovale) existed in fetal heart Left Ventricle Anterior to left atrium Forms the apex Longer and thicker walled than the right ventricle - Thickest walled chamber Pumps blood into aorta; Largest artery in body Like right ventricle also has: - Trabeculae carneae - Papillary muscle - Chordae tendineae Tangent: Right vs Left Ventricle Left ventricle - thicker wall, circular cavity Right ventricle - crescent shaped & wraps around LV 60 Mitral Valve Separate the left atria and ventricle 2 semilunar cusps Attached to left ventricular wall via chordae tendineae Aortic Valve Sits in between the left ventricle and the aorta 3 semilunar cusps Mechanism of action similar to pulmonary valve Small openings for left and right coronary arteries; Supply of oxygenated blood for the heart itself. Cardiac skeleton and valve - Valves are attached to heart via cardiac skeleton; 4 fibrous rings Systole - State of ventricular contraction Pulmonary and aortic valves are open allowing blood flow from ventricles out Tricuspid and Mitral valves are closed, blood stays in atrium Diastole - State of ventricular relaxation Pulmonary and aortic valves are closed, blood stays in ventricle. Tricuspid and mitral valves are open, allowing blood flow from atrium to ventricle Cardiac conduction system Initiates and coordinates contraction of atria and ventricles to pump blood - Sinu-atrial node (SA node) - junction of SVC & RA - Atrioventricular node (AV node) - interatrial septum - Atrioventricular bundle (Bundle of His) Gives off left and right branches - Subendocardial plexus (Purkinje fibres – left & right) SA and AV nodes Impulses begin at SA node (cardiac pacemaker), spread across atria, atria contract Activity in SA node stims AV node (near coronary sinus), ventricles AV bundle direct continuation of AV node – right and left bundles AV bundle and Subendocardial plexus Left AV bundle gives off branches that become continuous with subendocardial plexus; Allows for electrical impulses to spread through ventricles and muscles, causing contraction. 61 Coronary and Great vessels Pulmonary - blood flowing through the heart and lungs Systemic - Distribution of blood to the body 1. Deoxygenated blood enters RA 2. Blood passes the tricuspid valve into RV 3. RV pumps blood through the pulmonary valve into the pulmonary trunk to the left and right pulmonary arteries 4. Blood proceeds to the lungs and becomes oxygenated, losing CO2 5. Oxygenated blood enters LA via pulmonary veins 6. Blood passes the mitral valve into LV 7. LV pumps blood through the aortic valve into the aorta 8. The aorta delivers blood to the systemic circulation through a series of arteries 9. Capillaries within tissues supply blood to the body 10. Once blood reaches capil

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