CASE 1 REVISION - MUSCULOSKELETAL

“HIGH LEVEL” LEARNING OUTCOMES ANATOMY

Relate the anatomical structure of the limbs to their The knee is a synovial hinge type
function in health and in injury joint. The femur articulates with
Relate the motor and sensory innervation of the lower the acetabulum of the pelvis, the
limb to clinical deficits patella and the tibia.
Identify the different tissues present in the limbs at a The patella is the Femoral artery
macroscopic and microscopic level largest sesamoid and vein
Outline the physiology of pain mechanisms bone in the body. It only
Outline the molecular and cellular basis of inflammation articulates with the Deep femoral
and wound healing femur. artery and vein
Describe skin structure and function with reference to
inflammation and wound healing The tibia
Outline the mechanisms of action of common analgesics articulates with Great saphenous vein
and anti-inflammatory drugs the femoral condyles, the talus
Identify the structures of the limbs from radiological and the fibula.
images The joint capsule is made up of
an outer fibrous layer and an
inner synovial
HISTOLOGY (P) Anterior tibial artery
membrane. It
Perikaryon – aka the contains the patella, ligaments,
soma; the bulbous menisci and bursae.
end of the neurone Menisci are cresent shaped
containing the cell plates of fibrocartilage. There is a
nucleus. medial and lateral meniscus;
Nissl bodies are the granular areas of the perikaryon made of theya re thicker at edges. They
RER and free ribosomes for protein synthesis. reduce friction and act as shock
absorbers.
Oligodendrocyte – the schwaan cells of the CNS Tears are often due
Glial cells - Non neuronal cells in the spinal cord that form to twisting trauma.
myelin and give support to the neurones Causes pain, swelling
Neurofibrils – are made of neurofilaments (IF) that support and knee lock.
axons.
The epineurium is the CT
surrounding each nerve. A fascicle
is a collection of nerve fibres
surrounded by the perineurium,
and each nerve fibre has a CT
surrounding called the endoneurium.
They provide support and a barrier. Bursae are fluid/synovial sacs
Motor nerve endings has many projections that surround the joint cavity. They
to bring about effect, whereas sensory are between skin/tendon or
nerve endings converge to relay signal. tendon and bone. Reduces
friction.
Some axons aren’t myelinated (.e.g. c-pain fibres) as this Suprapatellar (between femur and
allows time for the person to react before intense pain. quads femoris)
A mesaxon is the parallel plasma membrane Subcutaneous (patella and skin)
of a single schwaan cell surrounding an Subcutaneous infrapatellar
unmyelinated axon. Schwaan cells have (patella ligament and skin)
neurolemmas (cell membrane) but
oligodendrocytes don’t.
Tay-Sachs – autosomal recessive – nerve cells deteriorate and
`’mental and physical abilities, there is excessive myelination
of nerve cells which causes death by age 4.
Osium staining might be showing adipocytes which get washed
out during staining.
Tendon (dense regular connective tissue) – encased in dense
irreg C-T sheaths. Mianly collagen.Groups of fascicles are
bound by epitenon. Endotenon – fine strands of CT between
each collagen fibre, and binds them together. Epitendon
encloses fasicles. Endotendineum CT separating fascicles.

Knee – L5, S1 (flexion), L3, L4 (extension)

 CASE 1 REVISION - MUSCULOSKELETAL

DIVERSITY OF MUSCULOSKELETAL DISEASES (L) CUTANEOUS WOUND HEALING (L)

Rheumatology deals with arthritis and MS disorders incl. Regeneration is the restitiution of tissue that us the same as the stuff
inflammation, degeneration, C-T diseases, soft tissue injuries removed/destroyed.
and back pain. For a tissue to regenerated the C-T and the stem cells are required. The
Investigations: history, physical C-T is also imp for cell migration and polarity.
examination, lab tests and imaging. Healing is fibroproligerative. It is the patching of tissue.
Symptoms: pain (SOCRATES), 1) Inflamm response removing dead and damaged tissue
stiffness (morning or evening), 2) Proliferation and migration of parenchymal and C-T cells
swelling/deformity, disability, 3) Angiogenesis (incl. endothelial progenitor cells from bone
wider systemic illness, sleep marrow) and granulation tissue
disturbance/how affecting life? 4) Collagen deposition
5) Wound contracting and strengthening
Look out for: swelling, muscle E.g. a liver becomes inflamed and fatty, and then scar forms to heal it
wasting, deformity, skin changes, causing cirrhosis. Scars are made of fibrous tissue.
tenderness, crepitus, ^ warmth
and stability. Healing by first intention is wounds that have been stitched
together and are clean.
Inflammatory rheumatic diseases Healing by second intention is when the wound has separated
Rheumatoid arthritis edges (causes more intense inflamm reaction, more scar formation
Sever inflammation of bursae, and granulation tissue)
synovial lining of joints and tendon Chemokine production attracts WBCs and COX2 production
sheaths. Affects all ages and is multifactorial produces PG and NO. P selectins are upreg P selectins(?)
in origin (incl. genetic predis). Synovitis causes Myofibroblasts contract to close the wound
erosion of articular cartilage, bone and joint. Using a skin graft means that it’s healing by 1st not 2nd intention
Chronic with exacerbations. Mainly MCPs Tissue remodelling is the replacement of granulation tissue with a
affected but also PIPs. scar. Collagen is syn 3-5 days after wound and as BVs `’, fibrous
Symmetrical, whole body tissue ^.
fatigue and stiffness in the Macriphages replace neutrophils after 3 days and cause
morning. Healthy synovial angiogenesis, antimicrobial activity (via ROS and NO), collagenase
fibroblasts become B cells and elastase to remove dead tissue and deposition of ECM.
(via IL-6), Th (via CCL 2,4,5
and CAM), neutrophils/PMN
(via CXC8) and PGE2 and INFLAMMATION IN RESPONSE TO INJURY (L)
Normal synovium
proteases. Acute inflammation
Crystal arthropathies (gout) Hyperplasia (^number), hypertrophy (^size), metaplasia (change in cell
Diseased synovium
Metatarsal phalangeal joint type), atrophy (`’ size and function).
at the base of big toes
Response to stress and noxious stimuli
commonly affected,
Cell injury can be due to hypoxia/ischemia, physical
inflammation
agents/trauma, chemical/infectious agents, immunological/genetic
caused by excess uric
changes or nutritional imbalances.
acid in blood being
Inflammation and repair are linked; inflammation helps repair
deposited as crystals
Inflammation and repair can be ad e.g. chronic inflamm
in joints and tissues.
Main characteristics: fluid exudation, plasma protein exudation and
Ankylosing spondylitis
emigration of WBCs.
Appears in early 20s,
Termination of inflammation is due to the mediators being broken
A=axial spine has
down and the offending agent being eliminated.
arthritis causing fusion
Neutrophils are involved in acute inflammation, and macrophages
of the spine.
in chronic inflammation
Psoriatic arthritis
VASCULAR: When there is damage there is transient
Arthritis due to the inflammatory condition; psoriasis.
vasoconstriction to prevent blood loss, but then vasodilation
Septic arthritis
(histamine and NO) causing ^ perm of vessels and therefore protein
Arthritis due to bacterial infection of the joint – usually staph
leakage. This allows WBCs through but also causes fluid to leak
or strep.
out. RBCs concentrate and become static allowing other cells to
Cardinal signs of inflammation: redness, warmth, swelling, come to the periphery.
loss of function and pain. CELLULAR: WBCs are allowed out of BVs and migrate towards
Fracture healing – 1) haematoma forms, 2) fibrocartilaginous chemotaxic signals. Chemotaxis occurs as the result of bacterial
callus forms (internal and external), 3) bony callus of spongy products or endogenous chemoattractants. Phagocytosis occurs,
bone forms, 4) fracture is healed and bone remodelled. The WBCs also degranulation to prod histamine and secrete lysosomes.
osteoid is the granulation tissue. Also PG synthesis.
Osteoarthritis – knee, hips, hands, spinal and apophyseal Chronic inflammation
joints. Destroys articular cartilage and all tissue in joint, Weeks/months of inflammation – simultaneous inflammation,
impaired tissue repair, also hypertrophy of subchondral bone tissue damage and repair.
and narrowing of Often begins low grad and worsens, but can follow from acute Inf
joint capsule. Affects more Caused by persistent infection, prolonged exposure to damaging
women, and is seen in elderly. agent or autoimmunity.
Lower back pain Monocytes in the blood become macrophages (these are the cells
Could be mechanical, of chronic inflammation). Also lymphocytes, eosinophils and mast
inflammatory, There are a lot of WBCs and tissue destruction but also
neurological, referred angiogenesis, C-T and fibrosis.
or a bony pathology Granulomatous inflammation – clumps of macrophages
(malignancy, SIRS (systemic I response syn) – fever, sepsis, ^Bp, chills, anorexia,
infection or metabolic) leucocytosis, leucocytosis and ^ acute phase proteins.
 CASE 1 REVISION - MUSCULOSKELETAL

NSAIDS (L) FACTORS AFFECTING WOUND HEALING (L)

 FAs are good biological mediators, they can be - Tissue environment
obtained from the cell membrane (where they are - How bad/how long the stimulus is causing the wound
glycerophospholipids) - If there are foreign bodies/enough blood supply
Phospholipase A2 - Disease (e.g. diabetes/steroids)
Cleaves FAs from the cell membrane generating the FA - Systemic = nutrition, metabolism, circulatory and hormones.
precursor arachadonic acid. AA is a polyunsaturated omega- - Local = infection, mechanical, foreign bodies and type of wound
6 FA. Lots of double bonds make it [rime for reactions Complications incl. deficient scar formation, excess scar formation (keloid)
(making it a good pre-cursor). and contractures (elastic tissue is replaced by fibrous).
Lipooxygenases (LOX) Wounds need oxygen for ATP, angiogenesis, helps with epithelium and
Converts AA > eicosanoids(by adding O2) -> leukotrienes keratinisation, collagen synthesis and fibroblast proliferation.
Leukotrienes are involved in chemotaxis, bronchoconstrict Ischemia and hypovolemia cause wounds to fail.
and vasc perm. They have inflammatory roles in airways. In the foetus there is no scarring but in older people there is
PGHS (prostaglandin- H synthase) `’angiogenesis, slower epithelialisation, `’inflamm response and collagen
Has 2 active domains: synthesis. Therefore older people have ^risk of a chronic wound with
COX domain excessive scarring.
which combines Diseases affecting wound healing:
O2 and AA, and the Diabetes – the structure and function of protein is altered and so keratin
peroxidase domain collagen are more rigid and there is also peripheral vascular disease due
which is activated to hyperglycemia.
by endoperoxide and Uraemia – urea is retained in the blood. Causes decreased healing;
converts it to a prostanoid. There are 3 isoforms of PGHS `’granulation tissue, `’collagen and tensile strength.
producing diff PGs.
Toxins and enzymes spread the subcutaneous infection, cellulitis can
PGHS1 – GI tract (patho=l is chronic pain and hypertension) lead to necrotising fasciitis and superantigens/endotoxins cause toxic
PGHS2 – reproductive (patho = inflamm, chronic pain, fever, shock. Bacteraemia (bacteria in blood) can lead to joint infection.
angiogenesis, neurodegredation and tumour growth) 4 classes of infection: contamination, colonisation, local infection and
Both do platelets, vascular and CNS functions. systemic/invasive infection.
PGH2 can be converted into…. Exogenous source such as a bit has lots of flora from the mouth –
PGD2 – bronchoconstriction, anti-platelet need tetanus, cleaning and antibiotics.
PGE2 – chemotaxis, histamine, inflammation Infection due to foreign bodies cannot be treated with antibiotics as
PGF2 – bronchoconstriction, uterine contraction they have no blood supply. Causes a prolonged inflamm response and
PGI2 – antiplatelet aggreg, vasodilation the foreign body has biofilm development (film of bacteria, fibrin,
TXA2 – platelet aggregation, vasoconstriction albumen and collagen).
Some prostaglandins have receptors, they are all GPCRs. Drugs: NSAIDs (`’inflamm), corticosteroids (`’inflamm and supreses
NSAIDs the autoimmune system, increases collagen synthesis, `’macrophage),
They inhibit the COX domain and prevent endoperoxide nicorandil (for angina) causes ulcers and immunosup = inhibit cell
production (PGG2 and PGH2). The `’ local inflammation, cycle and protein synthesis.
vasc permeability and decrease vasodilation. They aren’t as Wound contraction: first collagen is laid down then fibroblast apply
effective as steroids as steroids, inhibit the synthesis of tension to the matrix and draw wound together.
arachadonic acid via phospholipase A2. Abnormal scarring: Keloid – fibrotic growth from too much fibrin and
collagen; more comment in black women. Hypertrophic = raided&d red
 PGE2 from PGHS2 sensitises Aδ and C nociceptive Interventions: hyperbaric oxygen (lots of bacteria are anerobic), also
fibres to serotonin, bradykinin and substance P. NSAIDs wound dressing with silver, debriding a wound, using leeches, manuka
inhibit this production of PGE2. honey (antibacterial). Dihisense (wound falling open)
 NSAIDs can also decrease body temp by inhibiting the
PGHS-2 in the brain which generate PGE2 in response to Phases of wound healing
pyrogens. - Haemostatic phase (blood vessels increase in permeability and
 COX-1 is produced in most tissue, but COX2 is produced WBCs leak out)
at basal level and is only elevated during inflammation - Inflamm phase (see inflammation section)
 Asprin irreversibly inhibits the COX domain of PGHS1&2 - Proliferation phase (granulation tissue (a type of CT) forms from the
(acetylates the serine residue in COX). Comes from base of the wound up. It is type 3 collagen made by fibroblasts and is
willow tree bark. As it inhibits COX 1 it also inhibits for strength and structure. Angiogeneiss occurs. Bings O2 and
platelet aggregation and clotting. Causes ulcers because nutrients and removes waste. Looks moist, soft and pink. Collagen
COX 1 prod PG that produces protective gastric mucous. changes from type 3 to type 1. Epidermis then covers the granulation
Causes renal failure as PGs are syn in the kidney and tissue. Fibroblasts contract.
inhibition of COX-2 inparticular can cause renal ischemia - Epitheliation and remodelling (cells and caps degrade, type 3 -> type
because the PGs usually vasodilate in the kidney. 1 collagen (stronger), wound contracts = producing a scar.
 Ibuprofen is the racemate of S-enantiomer. Competitive
inhibition (competes with AA for COX domain) of
PGHS1&2. Derived from propanoic acid. Parkinsons?
 Rofecoxib – selevtive inhibition of PGHS2; good for
osteoarthritis but long term => MI/stroke.
 Paracetamol is not an NSAID. It has no anti-inflamm
properties but is a better anti-pyretic and analgesic
effects. Affects peroxidase domain of PGHS2 and 3.
 WHO pain ladder – mild pain = paracetamol/NSAID,
moderate = paracetamol and weak opioid (codeine
phosphate) and strong opioid (morphine/heroin).
 Reye’s caused by asprin <16yo. Causes fever, rash,
dizziness, brain problems, fatty liver, coma and death.
Caused by damage to mitochondria in the liver.
 CASE 1 REVISION - MUSCULOSKELETAL

INFLAMMATION HEALING OF KNEE (L)

Leukocyte extravasation (occurs mainly in venules) Knee M
1) During inflammation cytokines, cehmokines, IL-1 and - Actions: flexion and extension L
TNF-alpha stim endothelial cells causing them to - Has 3 articular parts; femorotibial (lateral
express selectins and medial) and femoropatellar
2) Selectins bind to glycolipids on WBCs and slow them - 3 bones: patellar, femur and tibia
causing them to roll along the BV - Has articular cartilage and menisci (medial and lateral)
3) Integrins (expressed by leukocytes?) allow the WBCs to - Ligaments: 5 extracapsular (patellar, fibial and tibial collateral, as well
bind tightly as oblique and arcuate popliteal), 2 intracapsular (A+P cruciate)
4) Cytoskeleton of WBC causes it to flatten against - It’s a synovial joint with bursae
endothelial cell and then creep out of BV by extending With a fracture, there will be a haematoma, then new bone will form at
pseudopodia between endothelial cells. external callus, and spongy bone will form internal callus, then bone will be
This is called diapedesis and uses mainly P-selectins. remodelled and healed.
Healing by 1st intention is via epithelialisaton, and There are 2 types of cartilage; fibro
second intenton is via granulation tissue formation. (menisci) and hyaline (articular
Subchondral cysts can form if synovial fluid enters the surface of bones). There are also
subchondral bone due to cartilage destruction. chondrocytes which produce
OA is central erosion and RA is marginal erosion. Ulnar cartilage and ECM containing
styloid process is often affected, and severe RA = ulnar proteoglycans. With cartilage the common injuries are torn menisci and
deviation. If DIP joint is affected think erosive OA. degen of articular cartilage. Because there is poor blood supply it takes ages
Inflammation: to heal. Can replace hyaline cartilage with fibrocartilage.
I. Vasoconstriction is a reflex of the ANS; lasts a few Ligaments – made of dense regular CT with more elastin than in tendons.
seconds. They also have a diff collagen composition. Fibroblasts
II. Arterioles dilate; ^blood flow and causing heat and lie in rows. Tears are healed by regeneration, scar Dense reg CT
redness – heat is bad for pathogens. formation or a combination. Poor regeneration as poor
III. Bradykinin, NO (from epi cells and mast and vascular supply. Stage 1 – inflammation; clotting, plug
endothelial cells) and histamine (mast cells) cause formation and necrotic tissue removal. Stage 2 –
vasodilation and increase vasc permeability. proliferation; fibroblasts accum, angiogenesis, granulation tissue formation.
IV. Diapedesis – see above; WBCs leave BVs. Stage 3- maturation; increasing tensile strength but decreasing BVs, matrix
V. Chemotaxis: WBCs find way to infection via and fibrblasts.
Chemotaxis (signals released by pathogen). Also
Synovium – is the soft tissue lining he joint cavity, it controls the
CYTOKines and C5a from complement. WBCs act via
environment and lubricates the joint. It’s almost acellular; only 1-2 cells
Gq system and there is an increase in IP3 causing
thick; it does have fibroblasts and macrophages. Synovitis is inflammation of
^Ca2+ from the ER amd actin and myosin allowing the
synovium, often due to RA or gout.
cells to move.
VI. Chemotaxic signals activate the neutrophils.
VII. Neutrophils phygocytose bacteria. They can destroy PAIN NOTES AND PSHYCOLOGY OF PAIN (L)
the contents via oxygen dependent or oxygen
independent means. Beecher & pain = soldiers; little pain because glad alive, civilians = lots
VIII. Oxygen dependant = hydrogen peroxide (H2O2) or of pain because pain is abnormal. ^pain sensitivity if depressed.
hydroxyl radical Pain is multidimensional; sensory (where it is), affective (emotions
IX. Oxygen independent – lysosomes, hydrolases, assoc with pain) and cognitive evaluative (feelings attached to pain)
defensins. Weich showed a `’ intensity in pain if looking at religious image;
descending pathways and prefrontal cortex modulate feelings- pain
TYPES OF WOUNDS Gate control theory (Melzack and Wall)– emotions influence pain and
Serous – production of clear fluid that comes from plasma our perceptions of pain. The gating occurs in the dorsal horn of the
or mesothelial cells of serous membranes. spinal cord. There are nociceptors and normal neurones that synapse
Fibrinous – comes after serous where there is a lot of fibrin on projector cells which go up the spinothalmic tract. There are also
deposition -> high vasc permeability; fibrin passes thru BVs. inhibitory cells in the dorsal horn of the spinal cord. So when there is
Suupurative/purulent – Lots of dead tissue and WBCs = pus normal perception of pressure then the gate is closed by the inhibitory
Ulcers – if damage occurs near epithelium and goes through neurone, but when there is pain the nociceptor activates the projection
layers then this cavity is an ulcer. cells and turns off the inhibitor to send the
Chemical mediators signal to the brain. This is why when we feel
pain and rub the area we activate the
Released from secretory granules:
pressure/normal receptors & `’pain
Histamine (mast cells/basophils/platelets)
Chronic pain can produce depression;
Serotonin (platelets)
people use affective words. They may
Lysomsomes (neutrophils and macrophages)
catastrophize it or fear of movement.
Synthesised Acute pain = sensory words.
PGs (WBCs, platelets & endothelial cells) Pain coping skills training: cognitive
Platelet-activating factors (WBCs and endothelial cells) behavioural therapy that has 3 parts:
Leukotrienes (WBCs) 1) rationale for the reason behind the
NO (macrophages) pain, 2)training in coping e..g
Cytokines (Macrophages, lymphocytes, endothelial cells) relaxing 3) behavioural rehearsal
All of the newly synthesised chemical mediators work to ^ Placebo – inhibits
vasc permeability) ascending nociceptive
Liver delivered to blood via plasma pathways, causes
Factor 12 activated by damage/collagen exposure also via endogenous opioid
bradykinin, activated the coagulation cascade. release and modulates
Complemnent activation; anaphylotoxins (C3a/C5a), MAC descending
and opsonisation. antinociceptive pathways.