Objective questions of Week 1 and 2 (LOC and IMM)

List the tissues that constitute the musculoskeletal system.

Epithelial tissue (glandular, GI, skin; where the cells have connection to the outside/lumen), Muscular tissue (skeletal, cardiac, and smooth muscle), nervous tissue (ganglion, cerebellum, sciatic), and connective tissue (tendon, bone, cartilage, locomotive).

Describe how some musculoskeletal tissues are designed and adapted for purpose.

There is a Cell to ECM ratio that plays a role in how a tissue works. Connective tissues have a low cell to ECM ratio, providing structural support and strength, while muscular tissues have a high cell density for contraction and movement.

Recognise that the extracellular matrices or musculoskeletal tissues are designed and adapted for load-bearing.

In musculoskeletal tissues, there is more ECM because it provides scaffolding to keep cells in a functional arrangement and to distribute and dissipate forces (load) imposed on the body by posture and locomotion. Connective tissue can modify their ECM to deal with load.

How are histological samples are prepared?

First, fixation must occur. The specimen will be fixed in formalin for ~ 24 hours and stored in 70% alcohol. The processing of the tissue takes place next, where the water in the tissue is removed and replaced with Histolene. The specimen is then embedded in paraffin wax. Once set, the sections are cut very thinly and then placed on a slide. Stain will finally happen and the wax has been dissolved, allowing for the structures to be seen.

Be able to identify the major tissue types in histological sections.

• Epithelia: form boundaries and barriers

• Connective tissue: contain proteins that hold everything together, cells which do particular jobs for the tissue and blood vessels, etc. which carry things in and out. The extracellular matrix is a network of proteins and ground substance to support everything.

• Muscle: three types (skeletal, cardiac, and smooth)

• Nerves: found in brain and nerve bundles, hard to see in most other tissues, and have receptors on the end of them.

Recognize the different types of epithelia.

• Comes in many different shapes and sizes

  • squamous: flattened nuclei

  • cuboidal: circular nuclei, square shaped

  • columnar: enlongated nuclei, column shape

  • stratified: layered

  • simple: single layer

Understand how the structures of tissues relate to their function.

Simple squamous epithelium can allow for gas and water to exchange between the lumen and the other cells Simple cuboidal epithelium can be for easier jobs, while simple columnar epithelium can sort through stuff and has more functions. Different sized/shaped epithelial calls come in different shapes due to different functions.

Describe the structure of a synovial joint.

A synovial joint is a joint characterized by a fluid-filled space called the joint cavity between the articulating bones. The range of motion in these joints can be defined largely by the shape of the articular surfaces. Ligaments can help support the joint and limit ROM.

Describe the structure, composition, and function of articular cartilage and synovial fluid.

The articular cartilage is the outer lining of bone in a synovial joint. The synovial fluid is a fluid that allows the joint to move freely and have nutrient provided to it. The composition of the articular cartilage and synovial fluid is water, collagen (specifically type II), proteoglycans, and chondrocytes. The function of these structures is to resist compression, provide resilience, provide support, and provide flexibility.

Describe the relationship between articular cartilage and subchondral bone.

Since articular cartilage does not have a pericardium, the cartilage has to receive nutrition through the subchondral bone. During osteoarthritis, the breakdown of one tissue affects the other tissue.

Describe where non-articular cartilage are found and discuss their functions.

Other cartilages are found in the nasal area, the ear, trachea, entheses (insertion of ligaments to bone), ribs/sternum, and growth plates. Some functions include elasticity, allowance of growth in certain places such as long bones or the ribs/sternum, or protection.

Describe the composition and arrangement of bone tissue within the bone organ.

Composition:

• Organic matrix: Mainly Type I collagen (provides tensile strength and flexibility).

• Mineral phase: Hydroxyapatite; provides rigidity and compressive strength).

Arrangement:

• Compact (cortical) bone: Dense outer layer organized into cylindrical units called osteons (Haversian systems), containing concentric lamellae around a neurovascular central canal, with osteocytes trapped in lacunae. Osteons are formed either through primary osteons or secondary osteons.

• Spongy (trabecular) bone: Porous inner network of bony struts (trabeculae) lining the marrow cavity

Describe bone modelling, remodeling, and when they occur.

Bone remodeling is bone resorption followed by formation. This allows damages to be repaired and occurs at the same location. This process occurs through the osteoclasts that resorbing bone and osteoblasts forming new bone. This is to allow the bone to adapt to changes (such as more pressure), repair, and maintain their function. Osteocytes can signal these changes to happen. Bone modelling is bone formation or resorption with a net change in bone shape. This evens out stresses and occurs at different cites.

Describe bone’s mechanical and endocrine functions.

Bones are used for many functions. Some include transmitting vibrations (the ear), space/protection for other organs, haematopoiesis (make new blood cells), mineral storage, tendon/ligament/joint capsule attachment, resistance to forces, and articulation. Bones are also affected by endocrine hormones such as sex hormones, PTH/vitamin D, FGF23, thyroid hormone, and much more.

Describe endochondral and intramembranous bone growth.

Endochondral ossification is how most of the skeleton is formed during embryonic development. It involves a cartilage template which is replaced by bone. The process is essential for bone growth and healing. MSCs differentiate into chondrocytes and secrete ECM rich in collagen II & aggrecan. Chondrocytes undergo an ordered process of proliferation, maturation, hypertrophy & cell death which defines the bone shape. Formation of primary ossification centre in diaphysis of the developing bone and invasion of blood vessels allows infiltration of osteoblasts and osteoclasts. Calcified cartilage surrounding hypertrophic chondrocytes is degraded by osteoclasts, which get replaced by bone and spreads longitudinally away from primary ossification centre. Formation of secondary ossification centres at the epiphyses. Bone replaces the cartilage and the epiphyseal plate is retained to allow further growth. When skeletally mature, the epiphyseal plates ossify.

Intramembranous ossification is found in flat bones like the skull. There is no cartilage template and MSCs differentiate directly into osteoblasts.

Describe the general organisation and functions of the nervous system.

The nervous system is split into three components; the sensory component (sensory organs/neurons), the integration component (spinal cord/brain), & response component (motor neurons and effector organs (muscles/glands)). The nervous system is also split into two systems: the peripheral nervous system (PNS; interface between CNS and the environment, including sensory and motor neurons) and the central nervous system (CNS; composed of the brain and spinal cord).

Describe the cellular composition of the nervous system and functions.

• Sensory fibres: carry sensory info from receptor organs

• Motor fibres: respond to the CNS input directly or the result of sensory input. somatic motor (voluntary system) and autonomic nerves (sympathetic and parasympathetic).

• Communication system through neurons (bipolar, unipolar, and multipolar)

• Support matrix through neuroglia types

  • Astrocytes - nourish and support neurones

  • Oligodendrocytes - increase speed of impulses during neurotransmission

  • Microglia - phagocytes that remove necrotic material

  • Ependymal cell - specialized cells of the epithelium lining CNS cavities

Describe the general structure of a nerve cell.

• Cell body (soma) - contains nucleus and other organelles

• Dendrite - Cellular extension containing microtubules and neurofilaments

• Axon - arise from the stoma or dendrite in a specialised region called the axon hillock (transport action potential)

• Schwann cell - comprise the myelin sheath

• Node of Ranvier - intervals between Schwann cells

• Axonal terminal - pre-synapse (connects with organ)

Explain how action potentials are generated and propagated.

The neuron has a phospholipid bilayer that is selective permeable to K+ (readily permeable) and Na+ (slightly permeable). K+ to continually enter the cells through electromotive forces due to negative environment. A pump moves Na+ out of the cell and move K+ into the cell. The charge distribution in the neuronal environment is not uniform having the resting membrane potential (RMP) be around -75mV. Action potentials are generated based on the different electrical charges and are split into three stages. First depolarisation occurs through stimulation which causes the permeability of Na+ to increase, raising the RMP. Critical voltage is reached (+30mV) and voltage-sensitive Na+ and K+ channels undergo conformational change and permeability to Na+ abruptly increase but K+ increase slowly. Repolarization occurs when the Na+ gates close at +35mV and K+ gates fully open removing K+ outside and transmembrane potential becomes negative. Action potential propagation dependent on myelination.

Describe the functional anatomy of a synapses and the neuromuscular junction (NJ).

A synapse is space between a neuron and a cell that allows for neurotransmitter communication. A specific type of synapse is NJ where the nerve is “connected” to a cell. An action potential causes an influx of Ca2+, causing fusion of vesicles full of neurotransmitters (NT; acetylcholine) with the presynaptic membrane, releasing them into the synaptic cleft. NT bind to the postsynaptic cleft receptors, leading to muscle contraction. NTs are removed by enzymatic breakdown (AchE) or reuptake across the presynaptic membrane for recycling.

Describe the production, release, action and degradation of the principal neurotransmitters (NT).

NTs are mainly peptides or derived from amino acids. There are three types: excitatory, inhibitory, and modulatory. NTs are synthesized in the nerve cell body and transported along the axon to the presynaptic terminal where they are stored in vesicles. The receptors in the postsynaptic membrane determine the effects of the NT.

Compare and contrast the structure and function of skeletal, smooth, and cardiac muscle.

Skeletal muscle has multiple peripheral nuclei (important for regeneration and adaptation), is voluntary, striated, and has regular parallel bundles. Cardiac muscle is also striated but have single central nuclei, involuntary, and has irregular arrangements with intercalated disks use to regulate ion movements. Smooth muscles have no striation, have single nucleus, are involuntary, and usually have longer contractions.

Describe gross and molecular skeletal muscle structure and how it is arranged in the locomotor system.

Muscles are structures made up of tiny building blocks. The muscle starts by being wrapped in epimysium and are a bundle of fascicle which are made of a bundle of fibre. Each fibre is made up of sarcolemma which are made up of myofibril, the source of contraction. The muscle cell is made up of mostly myofibril with the organelles fitting around the myofibril, including the nucleus, ER, and mitochondrial.

Describe the cellular and molecular mechanisms involved in muscle contraction.

The mechanism of muscle contraction is through the movement found in the sarcomere. The sarcomere is made up of filaments called actin and myosin. Actin is blocked by tropomyosin. Troponin controls the position of tropomyosin on the thin filament - here tropomyosin blocks the myosin binding site on the actin molecules. Calcium ions bind to troponin which changes the shape, causing tropomyosin to move away from the myosin binding site. Myosin heads bind to actin on the thin filament. Causes detachment of ADP and phosphate molecules. Myosin heads move, performing a ‘power stroke’ which drags the thin filament towards the centre of the sarcomere. ATP binds to myosin causing it lose affinity for actin and to detach from the actin binding site. ATP is hydrolysed into ADP and phosphate - this re-energizes myosin head to return to previous position. If calcium is present, the power stroke sequence happens again. If calcium is not present, actin is blocked by tropomyosin. Ca-ATPase hydrolyses ATP in order to take up Ca2+ ions back into the SR to end a muscle contraction.

Discuss the basic mechanism of synaptic communication and the events at a neuromuscular junction that lead to an action potential in a skeletal muscle fibre.

During synaptic communication, a neurotransmitter is released into the synaptic cleft and causes a cascade of molecule to enter into the other cell. A neuromuscular junction is a synapse between a nerve and a muscle fibre. Ca2+ moves into the neuron head, causing a voltage change. This voltage change causes the vesicles containing acetylcholine (Ach) to go to the synapse and diffuse into the synaptic cleft. There are receptors on the muscle side of the cleft that bind to Ach and allows Na+ to rush into the muscle fibre. This causes a voltage change, leading to an action potential.

Explain the mechanism of excitation-contraction coupling.

Excitation-contraction coupling is the process of depolarization of the postsynaptic membrane that results in a muscle contraction. First, a muscle action potential is propagated in the T-tubule. Depolarization of the t-tubule causes an opening of Ca2+ channels between the myoplasm and sarcoplasmic reticulum. Calcium is released from the SR (called calcium transient). Calcium binds to troponin, allowing actin to be open and allowing muscle contractions. After a contraction, calcium ions in the myoplasm are pumped back into the SR through Ca2+ ATPase which require ATP. Absence of Ca2+ ions in the sarcoplasm means the muscle no longer contracts.

Describe why skeletal muscle contraction requires energy, and discuss possible sources of this energy.

Energy is used in many steps of the muscle contraction. Energy is released from ATP hydrolysis for re-energizing the myosin had, ultimately providing the energy for cross bridge movement and force generation. Binding of ATP to myosin causes the release of the myosin head from actin (allowing repeated contractions). In the SR: Ca-ATPase hydrolyses ATP in order to take up calcium ions back into the SR to end a muscle contraction. ATP for muscle contactions come from metabolic processes, such as phosphorylation of ADP by creatine phosphate, oxidative phosphorylation of ADP in the mitochondria (aerobic respiration), and phosphorylation of ADP in the cytosol (anaerobic respiration).

Describe musculoskeletal “design” in mammals at the gross level and how it relates to function.

Muscles are different due to their function. Muscle architecture (i.e. arrangement of muscle fibres, muscle volume, moment arm, tendons, etc.) is a primary determinant of muscle function (force, work and power). Muscle fibre arrangement can be pennate (short fibres at an angle to internal tendon, which increase muscle physiological cross sectional area (PCSA). Muscle force is proportional to muscle PCSA (higher pcsa = higher force). Shorter fibres = shorter distance to contract = economical. Muscle fibre can also be parallel, where the fibres run with the line of pull of the muscle. More sarcomeres in series = greater total muscle fibre shortening = more potential for performing muscle work.

Describe the evolution of musculoskeletal design and locomotion in tetrapods.

Different animals with different locomotor needs will have different adaptations. Each joint has a ‘moment’ which is the potential for a joint to move. A ‘moment arm’ is the perpendicular distance from muscle insertion to joint centre of rotation. A joint moment is the muscle force times the moment arm. Large moment arms make it possible to lift large loads with smaller forces but large moment arms mean less absolute displacement (and therefore velocity) for a given force applied. There are evolutionary adaptations for cursoriality (cursor = animal that travels far/fast on land), such as leg elongation, which allow faster speed, distal segments lengthened and lightened, keeps mass proximal, reduces inertia/weight, and has some energetic implications. Rapid limb protraction can also be seen due to tendons where energy is stored slowly and released as a quick burst.

Give specific examples of how animal’s limbs are modified to accommodate specific postures and/or locomotion.

Horses limbs are modified to allow for long standing through the presents of tendons such as the reciprocal apparatus, where the flexion and extension of the stifle and hock are interdependent (linked; also known as the stifle locking mechanism).

Describe tendon structure (composition and organisation)

Tendons are specialized dense, fibrous connective tissues used for load bearing, undergoing elongation (“strain”) on the long axis. Tendons transmit tensile force from muscle to bone during locomotion. There are two distinct ends: myotendinous junction (MTJ) and osteotendinous junction (OTJ)/enthesis, with the in-between being the tendon body. The tendon is a multi-unit hierarchical structure, composed of collagenous and non-collagenous components. The whole tendon is surrounded in peritenon (made up of the epitenon (inside layer) and paratenon (outside layer)) with interfascicular matrix IFM) splitting up the fascicle bundle. The fascicular matrix (FM) and the collagen fibre make up the fascicle. The collagen fibre is made up of collagen fibril, made up of collagen microfibril, and ultimately made up of collagen. The main composition is collagen type one, water, proteoglycans, and glycoproteins. More lubrinin in the IFM allows for gliding resistance between fascicles while the more elastin enables better recoil.

Relate tendon structure to tendon mechanical properties and function.

All tendons have the same basic structure. However, energy storing tendons have several specializations, such as greater elongation and more elasticity. These adaptations allow for more energy storage, less muscular use (more energy efficient), and increase speed.

Explain how different tendon types (energy storing vs positional) are optimised for their function.

Energy storing tendons are used for energy storage from the energy from previous movement (stride), then release the elastic energy to recoil into the next stride. This increases the efficiency of high speed locomotion. They usually have a lower elastic modulus and high strain tolerated at normal and high loads. The extension mechanism is spring like fascicles with helix structure; high capacity for interfascicular sliding. The positional tendons are anatomically opposing tendons that transfer muscle force to distant bone to generate movement at the joint. The strain transfers from the muscle to the bone. They usually have higher elastic modulus to maintain position efficiently, needing minimal stain at normal load. The extension mechanisms have more interfibrillar sliding, with a low capacity for interfascicular sliding.

Describe the changes to tendon that occur during degeneration and their consequences to tendon function.

Degeneration is the loss of capacity for sliding between the fascicles, the loss of the helix structure in fascicles, decreased elastin content and organisation in the interfascicular matrix. This can increase tendon stiffness and decrease the ability to recoil/recover from loading.There is a significant decrease in loss of vasculature with aging, decreases in both vascular volume and vascular diameter, which likely has implications for healing in aged tendons.

Discuss the mechanisms leading to tendon injury.

Mechanisms of injury include:

• Overuse

  • Microdamage to extracellular matrix

    • Tendon has low rate of synthetic activity with the rate of damage may exceed rate of repair.

    • Leads to cumulative, interfascicular matrix, and collagen fibrils damage.

    • If overuse continues, damage accumulates and leads to clinical injury

    • Overuse causes cells to become rounder with an increase expression of matrix degrading enzymes and expression of inflammatory cytokines. Degradation exceeds synthesis.

  • Detrimental effect on cells

    • Direct

    • Hyperthermia-induced

      • During exercise, some energy stored in tendon is lost as heat, with the SDFT core temperature rising to 45 deg C. This can induce cell stress, damage, and death.

      • Activates degenerative pathways

• Age-related:

  • Extracellular matrix - loss of structural specialisations

  • Cells - reduced synthetic capacity and communication

  • Alterations in vascularity

• Combination of overuse and ageing

  • Higher risk of injury

Discuss the relationship between the immune system and infectious disease.

The main job of the immune system is to protect the body from infectious disease such as organisms and viruses. Pathogens are usually restricted to the epithelial surface but sometimes invades the tissues (either in they cytoplasm, tissue fluid, or in vesicles). The immune system is made up of white blood cells and lymphoid tissues. They do this through detection, destruction, and remembering infectious organisms. It is split into two categories: innate and adaptive immunity. Innate uses barriers and recognizes infections quickly through Pattern Recognition receptors (PRR). Adaptive is slower to react but more efficient and helps the innate system. The innate system can detect PAMPs on bacteria and virus structural proteins. Bacteria covered in capsules and viruses need adaptive immunity to fight these.

Explain what is meant by the term “antigen” and “epitope”.

An antigen is a structural protein found on pathogens. Lymphocyte receptors recognise the shape of a small region of the antigen called the epitope. Pathogens can have multiple antigens and each antigen can have multiple epitopes. Think about a blind man describing an elephant. Each one part of the elephant can be different. Each one is a different epitope of the elephant antigen.

Describe the strategies used by the immune system to detect and destroy foreign organisms.

The immune system can use antigen receptors to recognize a specific epitope. On the B-cell, there are B-cell receptors (surface immunoglobulin: slg) that has variable and constant regions. The variable regions have a V, D, J region that causes a lot of variability. These receptors binds to the whole antigen on the surface of the pathogen in the extracellular fluid. T-cells have a t-cell receptor (TCR). They also have a variable and constant domain which will signal the signalling molecule, allowing for more reactions to come. TCR recognize digested antigens presented on other cells from the innate immunity. The digested antigen is presented on the MHC and make a connection with the TCR called the immunological synapse.

Describe how lymphocyte selection processes and immunological memory play a key role in immunity.

Lymphocyte selection shapes the immune repertoire so the body can fight foreign invaders without destroying its own tissues. It occurs in two primary phases:

• Developmental Selection (Tolerance): Occurs in the primary lymphoid organs (bone marrow for B cells, thymus for T cells). It eliminates self-reactive lymphocytes via negative selection. Cells that bind too strongly to the body's own tissues are forced into apoptosis (cell death) to prevent autoimmune diseases.

• Clonal Selection (Activation): Occurs in secondary lymphoid organs (like lymph nodes) when a mature, naive lymphocyte encounters its specific foreign antigen. The unique match selects that individual cell, triggering clonal expansion (rapid multiplication) to create an army of identical cells to fight the active infection.

2. Immunological Memory: Long-Term Protection

Once an infection is cleared, the immune system preserves a permanent blueprint of the invader to ensure long-term defense.

• Memory Cell Formation: During clonal expansion, a fraction of the proliferating B and T cells differentiate into long-lived memory cells instead of active effector cells. These memory cells persist in the body for decades.

• The Secondary Response: If the same pathogen enters the body again, memory cells recognize it instantly. They bypass the slow, multi-day activation process required by naive cells, mounting a secondary immune response that is faster, stronger, and more prolonged. The pathogen is typically destroyed before symptoms even appear.

List the main components of blood and bone marrow.

Blood is made up of water, plasma, red blood cells, platelets, and white blood cells, each having specific jobs to help maintain homeostasis. Bone marrow is made up of different areas. One area is the Haematopoietic area which contain stem cells that differentiate into different blood cells. The vascular area is used to distribute nutrition and O2 for the stem cells but is also a way out for mature blood cells. Lastly, there are a few fat cells in the bone marrow.

Explain the main functions of blood.

Blood is used to maintain homeostasis (fluid, electrolyte, osmotic, and pH balance), is used as a transport system for nutrients, metabolites and metabolic waste, is used to facilitate endocrine signalling (hormone transport), transport gases (specifically O2/CO2 using RBCs and their hemoglobin), maintain integrity of the vascular system (through platelets), and for immunity and infection control (though WBCs).

Describe where and how blood cells are made, and how this is regulated.

Blood cells are made in bone marrow through stem cells. They are differentiated based on different signals such as hormones and cytokines sent by the body (ie. kidneys) when a specific cell is needed.

Discuss why haematology is important clinically, and how changes in blood cell numbers can be used to indicate disease and pathological processes occuring in the patient.

Haematology is clinically important as different levels in WBCs can explain what is happening internally in a patient. For example, increased neutrophils can indicate a bacterial infection. Haematology also includes blood cancers, red blood cell disorders, bleeding/clotting disorders, and bone marrow/lymphatic conditions.

Describe the function of different white blood cells in the immune response.

White blood cells have different jobs depending on what the body requires. For a bacterial infections, phagocytes such as neutrophils and macrophages (derived from monocytes) get rid of bacteria by eating them. Eosinophils, basophils, and mast cells fight against parasite, ganging up on them and release toxic and digestive enzymes. Lymphocytes (b-cells and t-cells) work to fight against viruses.

Explain the division of the immune system into primary and secondary lymphoid tissues.

• Primary lymphoid tissues: produce WBCs and train them for their specific purpose.

  • Bone marrow: produce WBCs and train b-cells

  • Thymus: train t-cells only, generating a unique antigen receptor (TCR), deciding whether to become CD4 or CD8 t-cells, teaching them to recognize MHC and to recognize self antigens

  • Bursa of fabricius: found in birds, similar function as the thymus but trains b-cells instead of t-cells

• Secondary lymphoid tissues:

  • Lymph nodes: filters tissue fluid (lymph) and traps foreign organisms. Lymphocytes enter via blood vessels to inspect the antigen present. The LN provides an environment for recognition of antigen by lymphocytes. It also provides the right conditions for lymphocyte activation and differentiation. Antigens can be swept into the LN in afferent lymph or brought to the LN paracortex through dendritic cells.

  • Spleen: Haematopoietic organ in foetal life, removal of particular material from bloodstream (foreign organisms and old RBCs), immune responses to blood-borne pathogens, and storage of RBCs and platelets.

  • Mucosal-associated lymphoid tissue (MALT; e.g. tonsils and Peyer’s patches): Initiate immune responses to organisms at mucosal surfaces.

Describe the basic structure and function of the thymus, spleen, and lymph nodes.

• Thymus

  • Located in the anterior mediastinum of the thoracic cavity. The thymus is arranged into lobules each with an outer, more densely cellular cortex and an inner, less cellular medulla. Immature t-cells leave the BM and enter the subscapular region. Here they proliferate before migrating through the cortex and medulla where they are ‘assessed’ for their suitability, before they are allowed to exit into the circulation as functional naïve t-cells.

• Spleen

  • Functions to filter blood, initiates immune response to blood-borne pathogens, remove senescent erythrocytes, and store RBCs and platelets. Located in the anterior left quadrant of the abdomen, it is surrounded by a fibrous capsule and the tissue is divided into two components. The red pulp functions as the RBCs/platelet store, the white pulp (rich in lymphocytes) is where the immune response occurs. The marginal zone (between red and white pulp) has macrophages for trapping particulate material and antigens. The white pulp is located around blood vessels forming structures called peri-arteriolar lymphatic sheaths (PALS)

• Lymph node

  • Bean-shaped structures, surrounded by a capsule, penetrated by many afferent lymphatic vessels that brings tissue fluid (lymph) into the LN and empty into a subcapsular sinus. Lymph is the filtered and leaves via an efferent lymphatic vessel located at the hilus, returning to the circulation via the tracheal and thoracic ducts. Within the paracortex, blood vessels from special structures called high endothelial venules that function to allow lymphocytes to exit the bloodstream and enter the LN to look for antigens. The interior of the lymph node is divided into a peripheral cortex and central medulla with the paracortex in between. B-cells are in the cortex and arranged into follicles. T-cells are scattered in the paracortex. The medulla contains macrophages and plasma cells. Dendritic cells can bring antigens into the LN. In healthy animals, the lymph nodes are small and contain primary follicles. When an infection happens, the LN enlarge. A central lighter region developing in the follicle called the germinal centre. Follicles contain germinal centre are called secondary follicles. Mature plasma cells migrate to the medullary cords where they secrete antibodies into the efferent lymph, which eventually reaches the blood.

Explain how lymphocyte migration via lymphatic vessels and blood results in efficient immune surveillance.

Lymphocytes spend their time visiting the various secondary lymphoid organs constantly. They travel through the lymphatic systems through lymphatic vessels and blood. They will visit various organs such as spleen, MALTs, and lymph nodes.

Recognize and classify fractures.

Fractures: break/discontinuity in a bone. Can range is size and severity. They could be located on the diaphyseal (shaft), metaphyseal, physeal (growth plate), epiphyseal, or the articular. Fractures can be open or closed (i.e. poking out of the skin or not), and can be simple or comminuted, transverse or oblique or spiral and can either be complete or incomplete.

Background of fracture healing.

Bones have a system where they will self repair themselves with bone compared to other tissues which repair with scar tissue. The bone recruits blood vessels and cells, remove devitalized or unnecessary tissue, make a mechanically competent scaffold, and re-shape the structure to form the most mechanically efficient structure. There are two types of healing: indirect and direct. These different types of healing are determined by strain/space between fractures (interfragmentary strain (IFS) theory). For indirect bone healing, the gap is >2mm. These types of fractures can be healed through external fixators (metal plates), external coaptation (casts), or plated fixation (bending plate). Indirect fracture healing tissue reduces IFS sequentially, cascade of progressively stiffer tissues. The fragment end resorption which increases the gap and decreases strain. It also increases external bone diameter (callus), increasing lever arm to resist bending. Indirect healing is faster, stronger, and long remodelling. Direct bone healing is the ‘artificial’ process of tricking the bone into performing bone turnover. The gap is <1mm. This will not cause a callus. Direct healing is usually weaker, slower, and longer remodelling phase to achieve full strength.

Awareness of different methods of fracture management.

There are external coaptation/casting which is an indirect immobilization of a limb to allow the fracture to heal. This is best for young diaphyseal simple minimally displaced fractures (below elbow/stifle, esp intact fibula/ulna) and metatarsal/metacarpal fractures. There is external fixation where there is an external rigid frame with pins that penetrate skin into bone. Best for open fractures, limbs with significant wounds, comminuted fractures, young animal fractures, and difficult bones to plate (funny shaped bones). Internal fixation pins/wires is where pins, wires and/or screws are used to repair fractures internally. Best for physeal fractures, small epiphyseal/avulsion fractures, and articular fracture repair. Internal fixation plates/screws is where metal plates are secured to bone with screws and allows for rapid return to function. Can be best for most fractures with appropriate consideration, but can not be used on Grade III open fractures or articular fractures. There is also cage rest, best for certain pelvic fractures and young animal single bone fractures (non-displaced, paired bone intact). Choosing which treatment can be based on patient factors, fracture factors, veterinarian factors, and client factors.