MSS Flashcards

Question

# MSS Joint disease and arthritis Skin changes in arthritis

Answer 1

* Atrophic (thin, wrinkled) skin, which is fragile and easy to bruise * Pale, translucent skin on the backs of the hands * Dry skin (xerosis) * Palmar erythema (red palms) * Raynaud phenomenon * Nail changes – brittle nails, onycholysis, nail ridging and splitting, clubbing, ventral pterygium. * Rheumatoid arthritis-related skin diseases

Answer 2

reactive arthritis, Behçet's disease, and systemic lupus erythematosus are associated with mouth sores, too

Answer 3

Inflammation -> **Sclera** -> Red eyes, pain, light sensitivity Inflammation -> **Uvea** -> (middle layer incl IRIS) -> Red cornea, vision loss (55% Macula damage) **uveitis can cause vision loss** **OTHER** Keratoconjunctivitis sicca **Episcleritis** (Conjunctiva) **Scleromalacia** (non-inflammatory form of anterior necrotising scleritis, Rare bilateral) **Scleromalacia perforans** a rare, severe eye disorder developing an autoimmune damage of episcleral and scleral performing vessels. *Type 3 Hypersensitivity*

Answer 4

Inflammatory Pain: worse at rest and better on movement Stiffness: Especially in the morning. Prolonged (>30 minutes) Swelling: Erythema Warmth Systemic symptoms

Answer 5

Non-inflammatory Pain: worse on movement/ weightbearing and relieved by rest Stiffness: <30 minutes

Answer 6

**Inflammatory** Rheumatoid arthritis Psoriatic arthritis Spondyloarthropathies Crystal arthritis Connective tissue diseases Septic **Non-inflammatory** Degenerative: osteoarthritis Trauma induced Chronic pain syndromes

Answer 7

* Can occur in infectious arthritis, gout, or trauma (not typical for RA or OA). * * Infections should be excluded * Trauma * Crystals: such as calcium pyrophosphate (pseudogout) and monosodium urate (gout) * Hemarthrosis

Answer 8

Osteoarthritis Infections: TB Tumours Monoarthritis refers to inflammation that affects a single joint instead of multiple joints. It may manifest in joint pain, swelling, and stiffness. Acute causes include infections, Lyme disease, crystal-induced arthritis, and trauma. Chronic causes include osteoarthritis, rheumatoid arthritis, and spondyloarthritis

Answer 9

* can be seen in reactive arthritis * Crystals: such as calcium pyrophosphate (pseudogout) and monosodium urate (gout) * Infections should be excluded

Answer 10

* arthritis of unkown origin * **osteoarthritis** * Can be seen in both RA (early stages) and OA. * oligoarthritis affects fewer than five joints * most often the large joints like the knees, ankles and elbows * the most common type of juvenile idiopathic arthritis (JIA).

Answer 11

* Autoimmune: JIA, SpA, Psoriatic, RA, CTD * Crystals: such as calcium pyrophosphate (pseudogout) and monosodium urate (gout) * polyarthritis affect five joints or more, and more often smaller joints in the hands and feet. * Infections (especially viral infections) should be excluded * Can be seen in infectious causes, or early RA but not typical for OA.

Answer 12

* polyarthritis affect five joints or more, and more often smaller joints in the hands and feet. * Autoimmune: JIA, SpA, Psoriatic, RA * Typical of RA.

Answer 13

**Rheumatoid Arthritis (RA):** Chronic Polyarthritis Chronic Oligoarthritis (less common) **Osteoarthritis (OA):** Chronic Monoarthritis Chronic Oligoarthritis **Less Common in RA and OA:** Acute Monoarthritis (rare in both) Acute Oligoarthritis (rare in both) Acute Polyarthritis (rare in both, but can occur in early RA)

Answer 14

Juvenile idiopathic arthritis (JIA) is a form of arthritis in children.

Answer 15

Spondyloarthritis (SpA), a family of inflammatory back diseases including ankylosing spondylitis

Answer 16

Reactive Arthritis

Answer 17

**FHx**: 3 fold increase in 1' & 2 fold increase in 2' relatives **Genes:** HLA-DRB1(the strongest). (MHC GENE) Others: CTLA4, PTPN22, STAT4, TRAF1-C5 (TNF family), PADI4 **DEMO** Age sex ethnicity **SHx** smoking, EtOH, obesity, infections and occupation (sillica)

Answer 18

**Background** * Epigenetic mod + susceptible gene * Self-protein citrullination * Loss of tolerance * Autoantibodies **Arthritis** * Triggers incl infection, microvasculature, neuroimmune, biomechanic (injury) * Synovitis * Sturctural damage * Applified by co-existing disease like osteroporosis and vascular disease * RECRUIT AUTOANTIBODIES TO SITE

Answer 19

* DAMPS PAMPs and Proteases * Circulating white cells include: Dedrite (CD80/8), Th1 and Th17, B Cell, **Plasmablast CD20 (Rheumatoid Factor),** Neutrophils (prostaglandins, ROS), Mφ (TLR, TNFα, CXC, IL-6), Chondrocytes and Osteoclasts * **Fibroblast-like synoviocyte (IL6, IL1, TNFα TGFΒ PDGF CXC)**

Answer 20

Insidious polyarthritis 70% Acute polyarthritis 20% Acute oligo or monoarthritis (not common) Palindromic rheumatism 10% Polymyalgic

Answer 21

MCPs, PIPs and MTPs, wrists, ankles and Knees 80%-90% Hip, elbow 50% Atlantoaxial joint 10% **Psoriatic Arthritishits DIPS, Rheumatoid hits PIPS and spares DIPS**

Answer 22

Boutonniere deformity Swan neck deformity Ulnar deviation of the fingers Z-shaped deformity of the thumb (Hitchhiker’s thumb) Claw toe deformity

Answer 23

* 75% of patients develop one or more extra-articular manifestations within 5 years of the onset of RA * Fatigue and weight loss (early on) * Rheumatoid Nodules (20%) at pressure sites * Normochromic, normocytic anaemia (Iron utilisation is impaired) * Thrombocytosis * Felty’s: RA, splenomegaly, neutropenia, inc infection risk * Pleural effusion: common, usually subclinical * Interstitial lung disease * Pulmonary nodules: rare * Pericarditis is most common cardiac manifestation * Cardiovascular disease * Ocular * Cervical cord compression * Carpal tunnel * peripheral neuropathy * Vasculitis incl nailfold splinter haemmorhages

Answer 24

* FBC * ESR, CRP * U&E, LFTs * Rheumatoid factor * IgM antibody directed against patients IgG immunoglobulin * High titre in extra-articular disease, nodules and in severe disease * Anti-CCP antibody Anti–cyclic citrullinated peptide (anti-CCP) * Image for joint changes and synovial fluid loss *

Answer 25

Psoriatic arthritis Reactive arthritis Arthritis of inflammatory bowel disease Crystal induced arthritis Osteoarthritis Viral polyarthritis: HBV, HCV, or human parvovirus B19 .. etc Connective tissue diseases: systemic lupus erythematosus (SLE), Sjögren's syndrome, dermatomyositis .. etc Polymyalgia rheumatica

Answer 26

Psoriatic arthritis Personal or family history of psoriasis (>90%) Seronegative Mono and oligoarthritis Asymmetric Large joints DIP affected Lower limbs Sacroiliitis and axial SpA Enthesitis are common Dactylitis 50% Uveitis

Answer 27

Rheumatoid arthritis Seropositive 80% Polyarthritis Symmetric Small joints DIP spared Cervical spine Enthesitis are not common Dactylitis 5% Sicca, episcleritis (5%) and scleritis (2%)

Answer 28

Seronegative High uric acid Initially monoarthritic – can become polyarticular Tophi on physical examination urate crystals in synovial fluids

Answer 29

Corticosteroids Conventional synthetic (nonbiologic) disease-modifying antirheumatic drug (sDMARD) therapies: methotrexate, sulfasalazine, hydroxychloroquine, leflunomide Biologic therapies (bDMARD): TNF inhibitors, interleukin (IL) 6 inhibitors, B-cell depletion therapy, T-cell costimulation blocker, and JAK inhibitors

Answer 30

Calcium pyrophosphate crystals in synovial fluids Neutrophils phagocytose Pro-inflammatory Chondrocalcinosis on radiographs Pc acute monoarthritis Risk: Trauma, Age, Metabolism, Genetic

Answer 31

**Acute** Monoarticular (1 joint) Polyarticular (> 1 joint) Causes Infection Injury **Chronic** Monoarticular (1 joint) Polyarticular (> 1 joint) Causes Immune-mediated e.g. RA Cartilage degeneration e.g. OA Other

Answer 32

1. Normal 2. Early fibrillation Chondrocyte loss 3. Deep fissuring Chondrocyte death Matrix loss

Answer 33

**Pain sensitivity** Neurochemical function Descending modulatory system **Joint Damage** Cartilage quality Joint laxity Geometry Inflamation **Psychosocial** Stress Emotion Exercise

Answer 34

**Pain sensitivity** Neurochemical function Descending modulatory system **Joint Damage** Cartilage quality Joint laxity Geometry Inflamation **Psychosocial** Stress Emotion Exercise

Answer 35

two families of metalloproteases – **MMPs** and the **ADAMTSs** – are responsible for the degradation of the major components of this tissue.

Answer 36

IL-1 IL-17 IL-18 Oncostatin M TNF

Answer 37

Activin CTGF FGF-2 IGF-1 TGF BMP-2,-4,-6,-7,-9,-13 | Remember B for build and G for Growth

Answer 38

IL-1ra IL-4 IL-10 IL-13

Answer 39

IL-4 IL-6 LIF

Answer 40

Injury, Aging, ROS, Mechanical stress,Degraded ECM Abnormal ECM synthesis, Inflammatory cytokines LPS, Genetics, Obesity Fragments of Aggrecan and Collagen activate DDR2 receptors Fragments of Fibronectin and hyalyronan activate TLR4 Fragments of fibromodulin activate complement ProMMP can activate for matric breakdown ADAMTS4,5 release activates for matrix breakdown

Answer 41

specific areas in joint cartilage and bone

Answer 42

Joint space narrows subchondral cysts cartliage loss Sclerosis

Answer 43

Doppler to show inflamation Lesions Ossification

Answer 44

Lining cell hyperplasia (border cells thicken) Increased vascularity (vascular structures/ cells) Subintimal fibrosis (fibrosis in layers) Mononuclear cell aggregates (white cells infiltrate)

Answer 45

Education, strengthening, lifestyle changes, fitness, weight management, pain killers, insoles, tens, support and brace, heat and cold

Answer 46

paracetamol topical nsaids Capsaicin oral nsaids inc COX2 inhibitor Inter aticular corticosteroid injections Opiods steroids

Answer 47

arthroscopy, cartilage repair, osteotomy, and knee arthroplasty.

Answer 48

Central pain processing ie) duloxetine, amitrityline Dorsal root ie) cannabidoids and opiates OA joint ie) effusion, hyaluronic acid, NSAIDs

Answer 49

Growth factor to replace cartilage Invossa gene therapy Joint distraction Steroids to control flares Capsaicin NSAIDS ?long term effects Monoclonal Ab against NGF Autologous chondrocyte implantation for Knee Chondral Defects

Answer 50

Integument, or integumentary system: refers to the skin, hair and nails. Largest and heaviest organ of the body – ~15% of adult weight.

Answer 51

**Barrier (protection), against:** Dehydration Infection Injury / abrasion Solar radiation **Thermoregulation** **Sensation Repair Vitamin D production**

Answer 52

Epidermis Dermis Hypodermis

Answer 53

Epidermis Dermis Hypodermis Hairs Glands Nails Sense organs

Answer 54

Outer epithelial layer With 4 sublayers 1. Basal layer(Stratum basale) 2. Stratum spinosum (spiny layer) 3. Stratum granulosum (Granular layer) 4. Stratum corneum (cornified layer)

Answer 55

**Single layer** containing stem cells (constantly proliferate) attached to dermis via basement membrane Main cell type **keratinocytes** Dynamic - Daughter cells constantly move “up” (*distally*) through the epidermis, differentiating as they go, until they are shed from the outer surface. This takes ~20-50 days.

Answer 56

2nd layer Thickest of living layers Lots of Desmosomes (juntions) Differentiating and moving distally; not dividing. Cells have many desmosomes (junctions), visible at high magnification as “spines” between the cells. Strong bonds holding the epidermis together.

Answer 57

1-4 layers of cells with granules of keratohyalin (pre-keratin) Lamellar bodies contain lipids (for waterproofing)

Answer 58

Outer protective layer Thicker depending on body site such as palmar thicker Squamous cells w/o nuclei Cornified with keratin protein Tough injury resistance Non polar lipids between layers | Cornified from Keras - horn (rhino horn)

Answer 59

Dendritic shape DOPA stain shows their form skin ***pigment*** No melanin – albino mammals Synthesises melanosomes and transfers melanosomes (pigment granules) to the basal keratinocytes via dendrites Do not cross to upper layers of skin They do not break the basal cell layer

Answer 60

the basal layer Capped for UV protection

Answer 61

Mφ like APC Dendritic shape, form network Stain pale.

Answer 62

Basal cells (somewhat stratum spinosum) Requires UV (higher in darker skin) NOT ACTIVE FORM Converted to active form in liver UK deficiency high.

Answer 63

Dense irregular connx. tissue w/ collagen Tensile strength Protection against abrasion Fibroblasts make collagen. Upreg in wound healing (revise) Elastin protein for elasticity (loss in UV/age) Blood and nerve supply Blood flow reg for thermoreg ***dermis fibroblasts fill gaps w new collagen. *** ## Footnote EPITHELIA NEVER HAVE BLOOD VESSELS

Answer 64

Wavy, resistant to shear forces Such as hands, feet Rete (*ree-tee*) Ridges in epidermis Dermal papillae (finger-like) in dermis

Answer 65

*aka fascia or subcutis* Fat cells- adipocytes (not seen on H&E as fat removed, cell border visible) containing glands, hair follicles, nerves, blood vessels. Often the thickest layer of skin. Thickness varies with age, body site, nutrition etc. Function: provides insulation, cushioning and energy storage.

Answer 66

Eccrine sweat glands Sebaceous glands Apocrine sweat glands

Answer 67

normal sweat glands. Watery secretion on to skin surface, cools body by evaporation.

Answer 68

secrete oily sebum (“lanolin”) into hair follicle. Conditioner for hair and skin, prevents dryness and flaking. Only from around puberty.

Answer 69

secrete into hair follicles. Found only in armpits and anogenital region. Oily fluid in humans, function unclear (contains pheromones in some mammals). Source of body odour after bacterial action. (Less odour in Asian people – enzyme difference.) Only after puberty.

Answer 70

Note much bigger diameter of apocrine than eccrine sweat glands. Both are coiled tubes, showing a cluster of circles or ovals of cuboidal epithelium in cross-section.

Answer 71

rudimentary in humans over much of body. (Unlike most mammals.) But keeps the head warm when present Hair follicles site of acne

Answer 72

Nail bed is skin under nail Nail plate is hard keratin Nail matrix where nail is formed The space under nail is hyponychium 3mm growth pmonth

Answer 73

* Thermoreceptors- dermis * Meissners corpuscle- dermis- touch and vibration * Merkel Cells- light touch- basal epidermis * Nocicpetor free nerve endings- mainly dermis, reach epidermis * Pacinian copuscle- pressure- hypodermis

Answer 74

* **Dehydration**- epidermis (keratin holds water) * **Infection**- epidermis impervious barrier, immune cells * **Injury**- All layers * **UV**- epiermis strat corneum and melanin * **Thermoreg**-hypodermis w fat and blood flow reg. * **Sensation**- nerves in layers * **Repair**- epidermis via proliferation but dermis fibroblasts fill gaps w new collagen. * **Vit D**- epidermis

Answer 75

Skin as a vital organ Normal effects of environment on skin Adaptations to temperature, friction, sun exposure **Abnormal effects:** failure of skin protective functions (introduction) Irritants, allergies and dermatitis Cutaneous infections Ultraviolet damage; burns, ageing and skin lesions including cancer **Skin will die if** Dehydration and shock Infection Heat loss and hypothermia (or sometimes hyperthermia due to impaired thermoregulation) Others: protein loss; electrolyte imbalance; high-output cardiac failure; renal failure.

Answer 76

Sweating & vasodilatation in heat; vasoconstriction in cold.Quite fast (minutes) Hyperkeratosis (callus): thickening of stratum corneum with rubbing or pressure (e.g. feet, guitarist fingers), or (slightly) after ultraviolet exposure. Slow (weeks) Tanning (melanocyte response) after ultraviolet exposure. Quite slow (days)

Answer 77

Drying: Waterproof epidermis + oil from sebaceous glands Friction, impact: Thick, regenerating epidermis; tough keratin Wavy epidermal-dermal border against shear forces Strong collagen fibre network in dermis Nails Cold: Subcutaneous fat, hair (head) Radiation/sunlight: Thick, regenerating epidermis; melanin Infections: Impervious epidermis; resident immune-system cells

Answer 78

Vessel walls **relax to increase arterial blood** flow and heat loss (when hot) **contract to decrease** blood flow (when cold) to the superficial (subpapillary) plexus just below epidermis. Hence skin goes redder or bluer. Hairless (glabrous) skin, e.g. palms, also has arteriovenous (AV) shunts or anastomoses between arteries. Shunts likewise open (hot) for additional heat loss, or close (cold).

Answer 79

The colour of human skin is due mainly to **melanin** (dark skin) and **haemoglobin** (light skin) Much** normal genetic variation** in the amount of melanin (many genes known) **Melanin** protects against DNA damage and thus skin cancer, especially in dark (black & Asiatic) skin: skin cancer incidence only 8-10% that of white people.

Answer 80

* UV radiation causes DNA breaks in keratinocyte * DNA breaks stimulate MSH: melanocyte-stimulating hormone * MSH leaves the cell to stimulate neighbouring melanocyte * MSH binds with receptor MC1R: melanocortin 1 receptor * The melanocyte via CAMP upreg ↑melanin synthesis & transfer and↑Cell division * Melanocytes then produce melanosomes whcih travel to basal keratinocytes * *Additional protection by epidermal thickening in response to UV. * MC1R gene – often mutated in humans with red or fair hair

Answer 81

More extreme form of hyperkeratosis. Reaction to excessive rubbing or scratching/ skin conditions

Answer 82

Occurs when too much exposure to a substance. Can still use it, but reduce amount. People vary in sensitivity Any of: Redness, itching, swelling, blistering and/or scaling NOT ALLERGY

Answer 83

Allergy to something that contacts skin - immune system involved Tiny amount may be sufficient Varies greatly between people May develop after long or short exposure Any of: Redness, itching, swelling, blistering and/or weeping Avoid allergen in future IS AN ALLERGEN

Answer 84

Washing powder Bleach White spirit SODA crystals Polish Chalk Hydrogen peroxide

Answer 85

metals leather shoe polish Latex

Answer 86

(nail fold infection-fungal or bacterial)

Answer 87

Fungal example: Tinea capitis (scalp ringworm)

Answer 88

Bacterial (children and elderky with thin skin)

Answer 89

Streptococcus

Answer 90

Virus example: Human papilloma virus (HPV) (warts)

Answer 91

Is a radiation burn Inflammation. Can include blisters, = epidermal cell death (severe DNA damage), or peeling (less severe DNA damage) “Ever sunburnt” associates with increased risk of skin cancer So does “ever used a UV sunbed below age 35” – by 75%

Answer 92

Sun allergy

Answer 93

Wrinkles - solar elastosis (loss of elasticity)

Answer 94

Benign proliferation of melanocytes Many or large naevi: risk factor for melanoma skin cancer

Answer 95

Involve a genetic component. Also linked to red/fair hair. Often MC1R gene variants Sun-exposed areas

Answer 96

liver spots, age spots

Answer 97

Dysplastic growth of keratinocytes

Answer 98

Open question: Ask patient to describe their skin problem Location/Distribution Onset/duration Associated symptoms: Itch, bleeding Changes/Progression Triggering factors Treatments they have tried Family history Impact on patient’s life

Answer 99

Expose all affected skin areas Inspect and palpate Size/Shape/Symmetry Type of rash/lesion (macular/papular/discoid/plaque) Colour Excoriated Distribution Palpation- texture, raised/ flat Nails/Scalp Dermatoscope (light and magnify)

Answer 100

Size/Shape/Symmetry Type of rash/lesion (macular/papular/discoid/plaque) Colour Excoriated Distribution Palpation- texture, raised/ flat | NEVER SAY RASH

Answer 101

* An inflammatory process affecting the skin and due to various factors, both internal and external * Interchangeable with the term ‘dermatitis’ * Itchy skin condition

Answer 102

* The most common form – affects 15% of population * In children – majority onset <5yrs, about 60% will clear by adolescence * Defect in skin barrier function causing skin to become more susceptible to irritation by soap and contact irritants, weather, temperature, etc * Chronic or acute flares * Usually associated with: * allergic rhinitis (hay fever) * Asthma * i.e. atopic tendency * ## Footnote Light skin- red patch. Dark skin- violaceous. (violet)

Answer 103

**Infantile atopic eczema:** Widespread dry scaly skin Can be weeping Often cheeks are first area affected Nappy area spared – moisture-effect **Toddlers/school-age children** More localised (flexural) and thickened, leathery (lichenified) lesions Scratch marks Elbows, knees, eyelids, ear creases, neck, scalp

Answer 104

Adults Commonly persistent localised eczema Recurrent secondary staphylococcal infection Major factor for irritant contact dermatitis, particularly hands

Answer 105

Topical steroid: mild moderate potent very potent Other – topical calcineurin inhibitors (Tacrolimus), oral antibiotics, antihistamines

Answer 106

Topical steroid: mild, moderate, potent, very potent Other – topical calcineurin inhibitors (Tacrolimus), oral antibiotics, antihistamines Phototherapy Systemic agents: Azathioprine, Methotrexate, Ciclosporin Biologics – Dupilumab Must meet specific criteria based on disease severity/quality of life Must have trialed other systemic(s) **A referral to a Dermatologist should be made in cases of:** Diagnostic uncertainty Severe eczema or poor response to topical therapy

Answer 107

Complications: Bacterial co-infection – impetiginisation Viral co-infection – eczema herpeticum Post-inflammatory hypopigmentation/hyperpigmentation Scarring Striae/skin atrophy from steroid use Depression/psychosocial impact

Answer 108

A chronic inflammatory disorder Common (1-2% of population) Focal, well-demarcated, inflamed, oedematous plaques covered with silvery-white scale Can affect any age No significant male/female difference Scaly skin condition **Distribution**: Variety of size and shapes Symmetrical Extensor surfaces Sacrum, scalp, ears, palms, soles Nails Environmental, genetic, immunologic factors

Answer 109

Disordered maturation of keratinocytes and reduced epidermal transit time from 30 days to 6 days Leads to hyperproliferation and thickening of the epidermis

Answer 110

Topical: Emollients Topical steroids Coal tar Salicylic acid Vitamin D analogues (Calcipotriol) Combination of above Dithranol Phototherapy Systemics: ciclosporin, methotrexate, acitretin Biologics: Monoclonal antibodies against TNF/IL Must meet specific criteria based on disease severity/quality of life Must have trialed other systemic(s) **Refer to Dermatologist if: ** Diagnostic uncertainty Severe psoriasis or poor response to topical therapy

Answer 111

EM Acne lesions Oily skin (seborrhoea) Open and closed comedones (blackheads and whiteheads) – arise when cells lining the sebaceous duct proliferate, and there is increased sebum production. A comedone is formed by the debris blocking the sebaceous duct and hair follicle **Papules** (small, tender red bumps) **Pustules** (white or yellow "squeezable" spots) **Nodules** (large painful erythematous lumps) **Pseudocysts** (cyst-like fluctuant swellings) Scarring and post inflammatory hyperpigmentation Individual acne lesions usually last less than 2 weeks but the deeper papules and nodules may persist for months.

Answer 112

Bacterial Highly Infectious Mainly children

Answer 113

. Chronic hives are welts that last for more than six weeks and return often over months or years

Answer 114

Intense and usually widespread reddening of the skin . Associated with exfoliation (skin peeling off in scales or layers.) Affecting 90% or more of the skin surface. Causes : Eczema Psoriasis Cutaneous T cell lymphoma- extensive, persistent, lympathadenopathy. Drug reaction 30% idiopathic

Answer 115

* ABCDE & MDT approach (HDU/ITU/plastics/dermatology) * * Discontinue all unnecessary medications * Monitor fluid balance – loss of fluid from skin results in electrolyte disturbance and dehydration * Maintain skin moisture and body temperature with wet wraps & greasy emollients * Antibiotics if superimposed bacterial infection * Antihistamines if itch (often severe) * Identify underlying cause and start specific treatment e.g. topical & systemic steroids/ciclosporin for atopic dermatitis or psoriasis. *

Answer 116

**HYPERSENSITIVITY** 2 types (both have classic targetoid lesions) 1. Major mucosal erosions and blisters, target lesions, bullae Cause: medications 2. Minor No erosions/blisters Targetoid lesions on extremities Cause: infections Management: Stop offending drug Treat underlying cause Supportive/symptomatic

Answer 117

Medical emergency! Variants of same condition with sheet like skin and mucosal involvement Nearly always caused by medication: 80% started 1-3 weeks before presentation Anyone on medication can develop SJS/TEN unpredictably - 40% caused by antibiotics. Development a while Skin pattern nasal vridge to epicanthal folds, under eye.

Answer 118

Investigations **SEPSIS 6** Skin biopsy Management – general measures ABCDE **Stop the drug** ITU, dermatology, plastics MDT management Sterile handling of patient – reduce infections Pain management Temperature regulation - warm room Nutrition (NG) & IV fluid management Non-adherent dressings Eye, mouth and genital care due to mucosal involvement Physiotherapy and psychiatric support

Answer 119

Autoimmune blistering skin condition Painful blisters and erosions on the skin and mucous membranes, most commonly inside the mouth IgG binds to Desmoglein 3 in the epidermis  keratinocytes separate from eachother and replaced by fluid Diagnosis: skin biopsy for direct immunofluorescence IgG antibodies on the surface of keratinocytes in epidermis Management: Symptom control + topicals + Systemic immunosuppression

Answer 120

Subepidermal autoimmune disease Risk factors: neurological conditions, psoriasis, medications Attack on collagen (BP180) in the basement membrane of the epidermis by IgG +/- IgE immunoglobulins Diagnosis: Direct immunofluorescence of a skin biopsy  linear deposition of IgG antibodies along the basement membrane (between the epidermis and dermis) Management: emollients, potent topical steroids+ systemic steroids/ doxycycline/ immunosuppressants

Answer 121

Ibuprofen is a common ‘over the counter’ NSAID. Usual dose 200-400mg tds PO. Standard group of NSAIDs. **Inhibit enzyme cyclo-oxygenase (COX).**

Answer 122

2 main types of COX enzymes: COX-1 and COX-2 COX-1 produces prostaglandins which maintain gastric mucosa, platelet-initiated blood clotting COX-2 generates prostaglandins which promote pain with inflammation.

Answer 123

Naproxen, Diclofenac, Indomethacin, Piroxicam, Celecoxib and Etoricoxib.

Answer 124

Side effects- headaches, dizziness, abdominal pain, diarrhoea, nausea and indigestion, bleeding, swollen ankles, chest pains, difficulty breathing, rash/sunlight sensitivity, high BP and effects on kidney.

Answer 125

Corticosteroids/steroids are synthetic versions of hormones. Administered orally e.g. prednisolone/dexamethasone, intramuscular/intra-articular methylprednisolone injections , topical creams/gels e.g. Eumovate, intravenous methylprednisolone.

Answer 126

Ibuprofen is a common ‘over the counter’ NSAID. Usual dose 200-400mg tds PO. Standard group of NSAIDs. **Inhibit enzyme cyclo-oxygenase (COX).**

Answer 127

Steroids are used sparingly in RA, but can be very beneficial, especially during a flare or when starting a new medication.

Answer 128

Relieve pain caused by inflammation rather than reducing the pathological inflammation and the RA degredation

Answer 129

* class of drugs used in treatment of inflammatory arthritis/other autoimmune conditions * rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis. * connective tissue diseases such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjogren syndrome (SS). * inflammatory myositis, vasculitis, uveitis, inflammatory bowel disease, and psoriasis. * conventional DMARDs * biological DMARDs *

Answer 130

7.5-25mg weekly PO, SC, IM BM suppression, effects on liver, GIT upset, rashes, pneumonitis, alopecia, headaches, menstrual cycle abnormalities, mood effects, infections, neoplasia

Answer 131

1-1.5G BD PO GIT upset, dizziness, cough, joint pain, rashes, allergic reaction, DRESS syndrome

Answer 132

200-400mg od PO GIT upset, rashes, tinnitus, retinopathy

Answer 133

10-20mg od PO GIT upset, alopecia, asthenia, weight loss, hepatotoxicity, high BP peripheral neuropathy, effects on blood count

Answer 134

1-3mg/kg check thiopurine methyltransferase (TPMT) level PO BM suppression, agranulotosis, nausea, diarrhoea, alopecia, infection, skin sensitivity, rash

Answer 135

1.5mg/kg BD with an increase to 2.5mg BD after 6 weeks, if needed PO High BP, renal effects, nausea, diarrhoea, gingival hypertrophy, excess hair growth

Answer 136

**MTX inhibits the enzyme dihydrofolate reductase, thereby depleting the pool of reduced folates** Common treatment for rheumatoid arthritis/inflammatory arthritis and other autoimmune diseases. 1940s developed as a chemotherapeutic agent. 1951 first used in rheumatic disease. Research studies established the response, efficacy and safety of ‘low dose’ Methotrexate compared to cancer treatment. **Prodrug**-active after polyglutamation in cells. Take up to **27.5 weeks to achieve a steady state.** Therapeutic effect-on average 12 weeks. 80-90% eliminated via kidneys; renal impairment may lead to increased levels and toxicity effects on the bone marrow/other adverse effects. Administered via oral, SC or IM routes with dose range from 7.5mg weekly to 25mg weekly typically used. NSAIDs can reduce excretion of MTX, can be used at lower doses.

Answer 137

Blocks folate metabolism Can also bind to folate dependent enzymes reduces amount of FH4 available for purine and pyrimidine metabolism; amino acid and polyamine synthesis.

Answer 138

MTX leads to **increased extracellular concentrations of adenosine**, which has anti-inflammatory effects. extracellular dephosphorylation of adenine nucleotides via ecto-5'-nucleotidase. **diminishing leukocyte recruitment** Rodents with no adenosine receptors have no anti-inflammatory effect from MTX (Montesinos et al. Arthritis Rheum 2003) Other mechanisms: decreased production of proinflammatory by activated T cells, inhibition of methylation, suppression of IL-1β production by mononuclear cells.

Answer 139

Sulfasalazine has anti-inflammatory effects by reducing oxidative, nitrative, and nitrosative damage. Leflunomide inhibits dihydroorotate dehydrogenase with inhibition of pyrimidine synthesis and preventing lymphocyte proliferation. Hydroxychloroquine is mild agent which inhibits intracellular toll-like receptor TLR9.

Answer 140

A group of therapies produced from living cells/their components using biotechnology. They act by targeting different aspects of the immune system which promotes inflammation.

Answer 141

Anti TNF therapies e.g. Infliximab (chimeric anti-TNF monoclonal antibody), Adalimumab (humanised anti-TNF monoclonal antibody), Etanercept (TNF fusion protein) IL-17 inhibitors e.g. Secukinamab (humanized monoclonal antibody to IL-17A, Ixekizumab JAK inhibitors e.g. Tofacitinib, Updacitinib, Filgotinib Apremilast (phosphodiesterase 4 [PDE4] inhibitor)

Answer 142

It activates signalling pathways: transcription factor activation (nuclear factor-κB), proteases (caspases), and protein kinases (c-Jun N-terminal kinase, MAP kinase). This activates the target cell and releases cytokines with the initiation of the apoptotic pathway leading to inflammation.

Answer 143

Activation of other cells (macrophages, T-cells, B-cells) Proinflammatory cytokine production (IL-1, IL-6), chemokine production (IL-8, RANTES), Expression of adhesion molecule (ICAM-1, E-selectin) Inhibition of regulatory T-cells, RANK-ligand expression upregulation, matrix metalloproteinase production and induction of apoptosis.

Answer 144

Dimeric human recombinant fusion protein Fc of IgG1 Binds TNFα β with high affinity No apoptosis of TNF expressing cells.

Answer 145

CHimeric mouse human mab (70%human) Fc of IgG1k Binds TNFα with high affinity Apoptosis of TNF expressing cells.

Answer 146

Humanised IfF1k mAb anti TNF Ab Binds TNFα β with high affinity Circulating or cell bound Apoptosis of TNF expressing cells.

Answer 147

Fully humanised IgG1k mAb AntiTNF Binds TNFα with high affinity Circulating or cell bound Apoptosis of TNF expressing cells.

Answer 148

Fab fragment of recombinant fully humanised mAn Anti TNF Fused with 400kDa peg moiety Binds TNFα β with high affinity Circulating or cell bound No apoptosis of TNF expressing cells. No complement or Ab toxicity

Answer 149

* Increased risk of infection, reactivation of tuberculosis, shingles, hepatitis B. * Demyelination, drug-induced lupus, increased risk of skin cancer, headaches, rashes, allergies, mood disorders. * Blood abnormalities-leucopenia, anaemia, thrombocytopenia. * Injection site reactions, impaired healing. * Avoid in history of multiple sclerosis, stage III/IV heart failure, lung fibrosis, recent history of cancer. * *

Answer 150

* Vasculitis * Connx tissue * Inflammatory Results in Local or organ damage which progresses with morbidity and mortality

Answer 151

Psoriatic arthritis: Joint inflammation affecting various parts of the body. Skin involvement: Psoriasis lesions, which may be widespread or localized. Nail changes: Psoriatic disease can lead to nail abnormalities. Psoriatic disease is characterized by chronic inflammation. Inflammation not limited to the skin and joints but can affect multiple organs. Association with comorbidities like cardiovascular disease and metabolic syndrome. Increased risk of developing conditions such as inflammatory bowel disease. Inflammation beyond the joints, affecting organs like the eyes (uveitis) and tendons (enthesitis).

Answer 152

Relative risk in first degree relative with Psoriatic Arthritis 30x more likely for PArhritis 5x more likely for Psoriasis

Answer 153

Frozen shoulder and tennis elbow 42% Rotator Cuff tears RR5

Answer 154

Genetic Factors: 1. Familial predisposition 2. Specific genetic markers associated with rheumatic diseases 3. HLA (human leukocyte antigen) associations B. Environmental Triggers: 1. Infections (viral, bacterial) 2. Environmental toxins 3. Smoking and other lifestyle factors 4. Hormonal influences C. Immunologic Dysregulation: 1. Autoimmune response 2. Abnormal immune cell function 3. Dysregulated cytokine production 4. Loss of self-tolerance D. Inflammatory Pathways: 1. Chronic inflammation 2. Tissue damage and repair mechanisms 3. Immune complex deposition 4. Synovial inflammation

Answer 155

Musculoskeletal Involvement: 1. Arthritis 2. Joint pain and swelling 3. Osteoporosis 4. Myositis B. Cutaneous Manifestations: 1. Rash 2. Ulcers 3. Photosensitivity 4. Vasculitis C. Systemic Involvement: 1. Fever 2. Fatigue 3. Weight loss 4. Lymphadenopathy D. Organ-Specific Features: 1. Renal involvement 2. Pulmonary manifestations 3. Neurological symptoms 4. Gastrointestinal issues E. Heterogeneity in Disease Progression: 1. Fluctuating disease activity 2. Remission and relapse patterns 3. Variable response to treatment

Answer 156

A. Atherosclerosis and Inflammation: 1. Chronic inflammation contributing to atherosclerotic plaque formation 2. Increased risk of coronary artery disease B. Endothelial Dysfunction: 1. Vasculitis affecting blood vessels 2. Impaired endothelial function contributing to cardiovascular complications C. Autoimmune-Mediated Cardiomyopathy: 1. Myocardial inflammation and damage 2. Heart failure as a complication D. Accelerated Atherosclerosis: 1. Increased cardiovascular risk due to chronic inflammation 2. Premature atherosclerotic events E. Monitoring and Management: 1. Regular cardiovascular assessment in rheumatic disease patients 2. Cardiovascular risk reduction strategies 3. Collaboration between rheumatologists and cardiologists for comprehensive care.

Answer 157

**PROTEIN MATRIX (25%)** Organic osteoid Type 1 collagen Flexible with tensile strength **MINERAL (75%)** Calcium and Phosphate = Hydroxyapatite Rigid High compressional strength Brittle **CELLS** Osteoblasts Osteoclasts Osteocytes Lining cells Bone marrow cells

Answer 158

**CELLS** Osteoblasts- synthesise bone and matrix proteins Osteoclasts- resorb boe Osteocytes-mechanosensors Lining cells-quiescent Bone marrow cells- middle

Answer 159

Osteoblasts- synthesise bone and matrix proteins Lining cells Osteocytes Apoptosis

Answer 160

Production of acid Dissolution of mineral Production of proteolytic enzymes Digestion of matrix Transcellular removal calcium, phosphate, matrix

Answer 161

**Trabecular** Lower density High surface area High remodelling rate Struts and plates **Cortical** Higher density Low surface area Low remodelling rate Haversian systems

Answer 162

* Quiescent= Resting * Resoption = osteoclast break * Formation = osteoblast build * Mineralisation = Calcium and Phosphate crystalise in bone Then back to Q

Answer 163

Hormones play a crucial role in bone homeostasis. Parathyroid hormone (PTH) and calcitonin, for example, regulate calcium levels in the blood, influencing bone turnover. Vitamin D, synthesized in the skin or obtained from diet, is essential for calcium absorption in the gut and bone mineralization.

Answer 164

The nervous system indirectly influences bone health through its control of physical activity. Weight-bearing activities and mechanical loading stimulate bone formation, while a lack of activity can lead to bone loss. Neuropeptides, such as substance P, are involved in the regulation of bone remodeling and can influence bone cell activity.

Answer 165

The hypothalamus-pituitary axis plays a role in bone regulation. **Growth hormone** (GH) from the pituitary gland stimulates bone growth and maintains bone density. **Sex hormones** (estrogen and testosterone) produced by the gonads have a significant impact on bone health. **Estrogen**, for example, helps maintain bone density in both men and women. **Adrenal hormones**, such as cortisol, can influence bone turnover. Excessive cortisol, as seen in conditions like Cushing's syndrome, may lead to bone loss.

Answer 166

* Oestrogen/androgens * Growth hormone/IgF1 * Calcitonin * Vitamin D

Answer 167

* Thyroxine * Glucocorticoids * Parathyroid hormone

Answer 168

When bones become osteoporotic and fragile, **the cortical bone (the outer shell) thins** and the struts within the **trabecular bone (inner mesh) also narrow** and become less strong. as ‘fragility fractures’ Eventually the architecture within the trabecular structure breaks down, leading to loss of bone strength and an increased risk fracture.

Answer 169

Measures Bone Mineral Density BMD Bone mass and bone mineral density are synonymous Quantity not quality The scan uses low dose radiation; is painless and silent and involves lying on a bed for a few minutes.

Answer 170

Osteoporosis is a systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to a high risk of fracture. 1 Often called a ‘silent disease’: people may not be aware that they have it until they break a bone

Answer 171

Normal T score does not exclude OP Artefacts falsely elevate BMD – eg spine OA or fracture Bone fragility can be due to poor bone architecture Low T score is not always due to osteoporosis Osteomalacia (undermineralised bone) also causes low BMD

Answer 172

* Age: The risk of osteoporosis increases with age, as bone density tends to decrease over time. * Gender: Women are at a higher risk of osteoporosis than men, especially after menopause when estrogen levels decline. * Family history: If you have a family history of osteoporosis, you may be more likely to develop the condition. * Race and ethnicity: Caucasian and Asian women are at a higher risk, but people of all ethnicities can develop osteoporosis. * Hormonal changes: Low estrogen levels in women, especially after menopause, and low testosterone levels in men can contribute to bone loss. * Body weight: Being underweight or having a small body frame can increase the risk of osteoporosis and fractures. * Dietary factors: A diet low in calcium and vitamin D can contribute to weaker bones. These nutrients are essential for maintaining bone health. * Physical inactivity: Lack of weight-bearing exercise or physical activity can lead to bone loss. Regular exercise helps in maintaining bone density and strength. * Smoking: Smoking has been linked to lower bone density and an increased risk of fractures. * Excessive alcohol consumption: Heavy alcohol intake can interfere with the body's ability to absorb calcium, leading to bone loss. * Certain medications: Long-term use of certain medications, such as glucocorticoids (corticosteroids), anticonvulsants, and some cancer treatments, can increase the risk of osteoporosis. * Medical conditions: Some medical conditions, such as rheumatoid arthritis, inflammatory bowel disease, and hormonal disorders, can contribute to bone loss. * Low body mass index (BMI): Having a BMI below the normal range may be associated with lower bone density and an increased risk of fractures.

Answer 173

* **Asymptomatic** Stage: Osteoporosis often progresses without symptoms until a fracture occurs. * **Fractures**: Fragility fractures, especially in the spine, hip, and wrist, are common. Spinal fractures can lead to height loss, kyphosis (curvature of the spine), and back pain. * **Pain**: Chronic back pain may occur due to vertebral compression fractures.

Answer 174

* **Bone Density Testing:** * Dual-Energy X-ray Absorptiometry (DEXA) scan measures bone mineral density (BMD) at the hip and spine. * T-scores compare BMD to that of a healthy young adult, while Z-scores compare to age-matched peers. * **Fracture Risk Assessment:** * FRAX tool assesses the 10-year probability of major osteoporotic fractures based on clinical risk factors. * **Medical History and Physical Examination:** * Evaluation of risk factors, family history, and presence of previous fractures. * **Laboratory Tests:** * Blood tests to assess calcium, vitamin D, and hormone levels. *

Answer 175

Bone metastases Myeloma screen CXR Need history and Ix 70% of vertebral fractures are not diagnosed BUT not asymptomatic Back pain is often not investigated Once diagnosed - Start osteoporosis treatment quickly to prevent further fractures occurring

Answer 176

* The T-score compares an individual's bone mineral density to that of a healthy young adult of the same gender. * It is expressed in standard deviations (SD) from the average peak bone mass. * * **Normal**: T-score above -1 SD * **Osteopenia** (Low Bone Mass): T-score between -1 and -2.5 SD * **Osteoporosis**: T-score -2.5 SD or lower * **Severe** **Osteoporosis**: T-score -2.5 SD or lower with a history of fractures

Answer 177

* The Z-score compares an individual's bone mineral density to that of an **age-matched and sex-matched** reference population. * Z-score results are used to assess bone density in the context of age. * A Z-score significantly below the expected range for age may indicate factors other than normal aging affecting bone density, such as underlying medical conditions.

Answer 178

**Present** Often asymptomatic until fractures occur Fragility fractures (fractures resulting from minor trauma or even normal activities) Common sites: spine, hip, wrist May lead to loss of height, stooped posture, back pain **Diagnosis**: Medical History and Physical Examination: Fracture history Risk factors (age, gender, family history, lifestyle, medications) Bone Density Testing: Dual-energy X-ray absorptiometry (DXA or DEXA scan) Measures bone mineral density (BMD) T-score compares patient's BMD to that of a young, healthy adult Laboratory Tests: Blood tests to rule out secondary causes (e.g., vitamin D levels, thyroid function) Imaging Studies: X-rays to detect fractures Vertebral fracture assessment (VFA) for spine evaluation Fracture Risk Assessment: FRAX tool: Calculates 10-year probability of major osteoporotic fracture or hip fracture Incorporates clinical risk factors with BMD results Additional Tests: Bone turnover markers (blood or urine tests) to assess bone metabolism Genetic testing in certain cases to identify rare genetic causes

Answer 179

**Teriparatide** daily subcut For 2 yrs **Romosozumab** mthly subcut Women only NICE approved in 2022 For 1 yr ## Footnote The most effective drugs have antifracture efficacy at all 3 sites

Answer 180

**Act on osteoclasts** Reduce bone resorption **Bisphosphonates** – inhibit farnesyl pyrophosphate synthase **Denosumab** - RANK ligand inhibitor ## Footnote The most effective drugs have antifracture efficacy at all 3 sites

Answer 181

**Osteoporosis drugs have varied half life in bone** **Bisphosphonates** Long half life in bone Concept of ‘drug pause’ after 5-10 years for mild osteoporosis **Non-bisphosphonates** have short half life in bone (quick onset, quick offset) High fracture risk if treatment stopped or paused Denosumab (risk of multiple vertebral fractures) Anabolics – teriparatide/romosozumab Don’t pause treatment when eg in hospital At end of treatment, need follow on treatment plan, no gap ## Footnote The most effective drugs have antifracture efficacy at all 3 sites

Answer 182

* Elderly – reduced dietary calcium absorption * * On steroids cause a negative calcium balance * * On parenteral antiresorptives * Reduces Osteoclastic bone resorption * Less calcium released by osteoclasts from skeleton ## Footnote The most effective drugs have antifracture efficacy at all 3 sites

Answer 183

* **Inspection** * No wasting or fasciculation * **Tone** * Hypertonia * **Power** * Weakness * **Reflexes** * Hyperreflexia * Extensor plantar responses (Babinski’s sign positive) * Clonus

Answer 184

* **Inspection** * wasting or fasciculation * **Tone** * Hyportonia * **Power** * Weakness * **Reflexes** * Hyporeflexia or areflexia * Flexor plantar responses (Babinski’s sign negative) * No clonus

Answer 185

Root Lesion Disc Herniation

Answer 186

Plexus Lesion Brachial Neuritis

Answer 187

Single nerve (median nerve palsy, facial palsy)

Answer 188

Several induvidual nevres Assymetric Vasculitis

Answer 189

umerous peripheral nerves at the same time distal symmetrical motor and sensory

Answer 190

Dorsal root ganglia Purely sensory neuropathy Paraneoplastic syndrome

Answer 191

Myelin sheeth pathology Guillian Barre syndrome

Answer 192

Axonal degeneration (diabetes)

Answer 193

1. Motor ± Sensory ± Autonomic 2. Distal pattern of weakness 3. LMN lesion (wasting, fasciculation, hypotonia, hyporeflexia, flexor planter response) 4. Gloves and stocks pattern of sensory loss 5. High-steppage gait

Answer 194

1. Motor (Normal reflexes and Normal sensory exam) 2. Proximal pattern of weakness (Difficulty in combing Hair, standing from a Chair, climbing a Stair). 3. Waddling gait. 4. Positive Gower sign.

Answer 195

1. Motor (Normal reflexes usually and normal sensory exam) 2. Proximal pattern of weakness (Difficulty in combing Hair, standing from a Chair, climbing a Stair) 3. Fatigable weakness 4. Ptosis, complex ophthalmoplegia, blurring of vision. 5. Dysarthria, dysphagia, dyspnea

Answer 196

Claw not benediction

Answer 197

wrist drop

Answer 198

Hx (alcohol, diabetes etc…) FBC, LFTs, GGT and U+E’s TFTs Glucose or HBA1C Plasma B12 and folate HIV serum protein electrophoresis and immunoelectrophoresis ESR, CRP (vasculitic screens if indicated e.g. ANA, ANCA, ENA etc…) Urinalysis CXR Nerve conduction studies and electromyography

Answer 199

Gowers SIgn present

Answer 200

Electromyography (EMG) and nerve conduction studies (NCSs) are valuable diagnostic tools that help neurologists locate and determine the causes of diseases that affect muscles and peripheral nerves While EMG and NCSs are different tests, they're often used together because the information gained from each test. * **EMG** used to diagnose myopathies * to differentiate between myopathy and neuropathy * to detect widespread denervation that would be present in motor neuronopathies such as motor neuron disease.

Answer 201

Spinal Cord Injury (SCI) Spinal Cord Compression Transverse Myelitis Cauda Equina Syndrome

Answer 202

Herniated Disc Radicular Pain (Sciatica) Foraminal Stenosis Nerve Root Avulsion

Answer 203

Brachial Plexus Injury Lumbosacral Plexopathy Thoracic Outlet Syndrome Diabetic Amyotrophy

Answer 204

Peripheral Neuropathy Carpal Tunnel Syndrome Guillain-Barré Syndrome Charcot-Marie-Tooth Disease Neuropathy due to Chemotherapy

Answer 205

Myasthenia Gravis Lambert-Eaton Myasthenic Syndrome (LEMS) Botulism Congenital Myasthenic Syndromes

Answer 206

Myasthenia Gravis Lambert-Eaton Myasthenic Syndrome (LEMS) Botulism Congenital Myasthenic Syndromes

Answer 207

**dense and solid and surrounds the marrow space** **Osteon**- fundamental functional unit of compact bone. containing concentric rings of bone matrix called **lamellae**, which surround a central canal **central canal**of blood vessels and nerve, lymphatic vessels, providing nutrients and oxygen to the bone cells (osteocytes) **Canaliculi** are tiny channels that radiate from the central canal to the lacunae (small spaces) where osteocytes are located. These channels allow for the exchange of nutrients, gases, and waste products **Lacunae** are small, fluid-filled spaces within the bone matrix that house osteocytes—mature bone cells.

Answer 208

**Fibrous Layer:** The outer layer of the periosteum is made up of dense, irregular connective tissue. This fibrous layer serves as a protective barrier, helping to shield the bone from external forces and providing structural support. It also contains blood vessels, nerves, and lymphatic vessels that supply the bone with nutrients and oxygen. **Osteogenic Layer:** The inner layer of the periosteum, known as the osteogenic layer, is rich in cells involved in bone formation and repair. These cells include **osteoblasts**, which are responsible for producing new bone tissue, and osteogenic cells, which are undifferentiated stem cells that can differentiate into osteoblasts. The osteogenic layer plays a crucial role in the growth and repair of bones. In children this is responsible for bone diameter increasing.

Answer 209

**Bone Repair and Growth**: The osteogenic layer of the periosteum is involved in bone repair and growth. **Osteoblasts** in this layer contribute to the formation of new bone tissue during processes such as bone remodeling, fracture healing, and bone development in growing individuals. **Attachment for Ligaments and Tendons:**Ligaments (connecting bone to bone) and tendons (connecting muscle to bone) often attach to the periosteum. This attachment helps stabilize the bones and facilitates movement.

Answer 210

The two main cells are: **Osteoclasts** (chew) They break down and reabsorb bone tissue by secreting enzymes and acids that dissolve the mineralized matrix. *Osteoclasts are larger, multinucleated cells with a ruffled border. The ruffled border increases the cell's surface area* **Osteoblasts** (build) They secrete organic components of the bone matrix, including collagen, and actively participate in the mineralization of bone *Osteoblasts have a cuboidal or columnar shape with abundant rough endoplasmic reticulum and Golgi apparatus. *

Answer 211

**Calcitonin**: Inhibits osteoclast, stimulates osteoblast **PTH** Stimulates osteoblasts indirectly, Directly stimulates osteoclast PTH helps regulate calcium levels **Oestrogen** Stimulates osteoblast, Inhibits osteoclast **Vitamin D** Promotes the absorption of calcium and phosphate at osteoblasts Indirectly inhibits osteoclast **Mechanical Stress (Weight-Bearing Activity):** stimulates osteoblast activity, indirectly inhibit osteoclast **Cytokines (e.g., Interleukin-1 and Tumor Necrosis Factor-alpha):** May inhibit osteoblast activity. stimulates osteoclasts

Answer 212

**Collagen**: provides flexibility and tensile strength **Osteoblasts**: bone-forming cells. produce collagen and other proteins **Osteocytes**: maintain the daily metabolism of bone tissue producing and maintaining the extracellular matrix. **Osteoid**: primarily composed of collagen fibers, glycoproteins, and proteoglycans. It provides a scaffold for mineralization and gives bones their flexibility.

Answer 213

**Hydroxyapatite:** crystalline structure composed of calcium and phosphate ions. provides bones with hardness and compressive strength. **Mineral Salts:** mineral salts, including calcium carbonate and magnesium hydroxide.

Answer 214

bONE = type ONE collagen

Answer 215

multiple components to reduce stress and increase strcutre

Answer 216

**identical structure** collagen and minerals stick identical collagen fibrils macroscopic/cellular level of organisation is different. Trabecular bone has a porous, lattice-like structure, while cortical bone is dense and compact. Trabecular bone is found at the ends of long bones, in the interior of flat bones, and in the spine, while cortical bone forms the outer layer of all bones and the diaphysis of long bones.

Answer 217

**1. haematoma and tissue destruction** vessels torn, bone at fracture end dies due to the lack of blood supply **2. inflammation** inflammatory mediators released, proliferation of cells from endosteum, growth of new capillaries **3. callus** soft woven material with immature fibroblast chondrogenic, osteogenic cells and osteoclasts. Neogenesis b/n ends, periosteum reforms **4. consolidation** continuing osteoblastic and osteoclastic activity, woven bone transformed to lamellar bone. Bony matrix appearing **5. remodelling** fracture bridged by solid bone continuous reshaping of bone haversian system restored

Answer 218

**Subcutaneous** low blood (talus, scaphoid) the healing phase is longer and remodelling is long. **Remodelling** can take up to 2 years **4-6weeks** in a small bone in a healthy child before use again. **HEAL** when the bone is structurally sound to function. (NOT ALWaYS remodelled)

Answer 219

**BONES RESPOND TO STRENGTH** Trabecular oganisation to respond to density for higher load stress Osteocytes know "up and down" They respond to direction of load.

Answer 220

1. patient survival reusucitate etc 2. limb survival vascularity compartment syndrome 3. functional survival fracture union muscle/tenson units nerve 4. infection prevention soft tissue coverage

Answer 221

*antibiotics *anti-tetanus *a splint *a photograph *a barrier dressing *an operation

Answer 222

"*raised pressure in a closed fascial compartment that exceeds capillary perfusion pressure*" * Faschia does not allow osmotic transfer * So raised pressure can only go to capillaries * If it overwhelmes capillary load (arterial bleed into comparment) * It collapses venous outflow * Arterial continues * Venous continues to collapse * INCREASE PRESSURE * PAIN PAIN PAIN * Pulse can still be present, but if pulse lost >6 hours and ischaemia. limb loss *** Passive stretch gives pain** (cramp is minor but similar mechanism of stretch)

Answer 223

*nothing *splint *plaster of paris

Answer 224

*external fixator *internal plating *intramedullary nailing *joint replacement

Answer 225

reduces infection rate

Answer 226

no wait for fracture healing

Answer 227

longest part atrophy of joints and muscle aim: normal function asap * physiotherapy when splintage is removed to enable full joint function * encourage proprioception

Answer 228

* age * co-morbidities * vascular disease * diabetes * drugs * smoking * associated injuries (iss) * surgical skill / experience * local resource

Answer 229

Rarely pt fault Smoking and alcohol Diabetes NSAIDs impair healing as stops the cascade early fear of using the limb- trabecular stimulatio

Answer 230

pathological increase of osteoblasts- rigid "petrified" bones

Answer 231

Abnormal lateral curvature of the spine.

Answer 232

Shortening or stiffness of the neck muscles, leading to limited neck movement. Brevi- short, Collis- Collar. Short Collar. Stiff Neck

Answer 233

Absence of one or more limbs.

Answer 234

Ectrodactyly refers to missing digits or portions of limbs, while polydactyly refers to extra digits.

Answer 235

Developmental anomaly characterized by a split or cleft in the hand or foot.

Answer 236

Genetic disorder resulting in dwarfism due to impaired bone growth.

Answer 237

**Keratinocytes**: Predominant cell type in the epidermis responsible for producing keratin, a structural protein. **Melanocytes**: Cells that produce melanin, responsible for skin pigmentation. **Langerhans** cells: Dendritic cells involved in immune responses. **Merkel** cells: Sensory cells associated with touch sensation.

Answer 238

* Keratinocytes originate from basal cells in the stratum basale, where they undergo mitosis. * As keratinocytes mature, they move upward through the epidermal layers: stratum spinosum, stratum granulosum, and stratum corneum. * In the stratum corneum, keratinocytes are fully keratinized and eventually shed from the skin surface.

Answer 239

**Epidermal Barrier:** The outermost layer of the skin, the stratum corneum, acts as a physical barrier, preventing the entry of pathogens and harmful substances . **Sebum Production**: Sebaceous glands secrete sebum, which helps lubricate the skin and maintains its waterproof barrier function. **Immune Response**: Langerhans cells and other immune cells in the skin mount an immune response against pathogens. **pH Regulation:** The slightly acidic pH of the skin inhibits the growth of harmful bacteria.

Answer 240

* **Spinal Cord**: Injury or compression causing sensory, motor, or autonomic dysfunction. * **Nerve Roo**t: Radiculopathy from compression, leading to pain and sensory/motor deficits. * **Plexus**: Brachial or lumbar plexopathy causing arm or leg weakness, numbness, or pain. * **Peripheral** Nerves: Neuropathy or Guillain-Barré syndrome causing limb tingling, numbness, or weakness. * **Neuromuscular** **Junction**: Myasthenia gravis or Lambert-Eaton syndrome resulting in muscle weakness. * **Muscle**: Muscular dystrophy or myositis causing progressive muscle weakness and degeneration.

Answer 241

Facial nerve (CN VII); Unilateral facial paralysis, inability to close eye, loss of forehead wrinkles, loss of taste on anterior 2/3 of tongue; Idiopathic, possibly viral (HSV), Lyme disease

Answer 242

Radial nerve; Wrist drop, loss of sensation over dorsal hand, weakness in extension of wrist and fingers; Humeral fracture, prolonged compression (e.g., 'Saturday night palsy')

Answer 243

Ulnar nerve; Claw hand deformity, loss of sensation over medial 1.5 fingers, weakness in finger abduction/adduction; Elbow injury (e.g., cubital tunnel syndrome), wrist injury

Answer 244

Median nerve; Ape hand deformity, loss of thumb opposition, weakness in flexion of lateral fingers, sensory loss over lateral 3.5 fingers; Carpal tunnel syndrome, forearm fractures

Answer 245

Common peroneal (fibular) nerve; Foot drop, loss of sensation over lateral leg and dorsum of foot, difficulty dorsiflexing and everting foot; Fibular head fracture, prolonged leg crossing

Answer 246

Sciatic nerve; Weakness in knee flexion, foot drop, sensory loss over posterior thigh, leg, and foot; Hip dislocation, herniated disc, intramuscular injection injury

Answer 247

Long thoracic nerve; Winged scapula, difficulty raising arm above head; Trauma to shoulder, surgical injury, repetitive overhead activities

Answer 248

Axillary nerve; Deltoid muscle atrophy, loss of abduction of shoulder, sensory loss over deltoid region; Shoulder dislocation, surgical neck fracture of humerus

Answer 249

Femoral nerve; Weakness in hip flexion and knee extension, sensory loss over anterior thigh and medial leg; Pelvic fracture, retroperitoneal hematoma

Answer 250

Obturator nerve; Weakness in thigh adduction, sensory loss over medial thigh; Pelvic surgery, pelvic trauma

Answer 251

Oculomotor nerve (CN III); Ptosis, 'down and out' eye position, dilated pupil, loss of pupillary reflex; Aneurysm, diabetes, trauma

Answer 252

Trochlear nerve (CN IV); Vertical diplopia, difficulty looking down and in, head tilt to compensate; Trauma, congenital, microvascular disease

Answer 253

Abducens nerve (CN VI); Horizontal diplopia, inability to abduct eye, medial deviation of eye; Increased intracranial pressure, trauma, microvascular disease

Answer 254

Lateral medulla; Ipsilateral facial pain and temperature loss, contralateral body pain and temperature loss, dysphagia, hoarseness, vertigo, ataxia; Posterior inferior cerebellar artery (PICA) stroke

Answer 255

Medial medulla; Contralateral hemiparesis, contralateral loss of proprioception and vibration, ipsilateral tongue deviation; Anterior spinal artery stroke