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PRECLINEAZY Case 1 – P art 2 Presenter: Rayyan Malik Case 1 Todays Session will cover Immunology Recap/Inflammation Bones and Disease Radiology of the Lower LimbImmunology Cytokines & Chemokines Pro-Inflammatory Anti-inflammatory IL-10, TGF-B Plasma-derived Cell-derived C3a + C5a, bradykininsTNF-A, Histamine, prostaglandins, NO TNF-A, IL-1 CXCL8 ↑Prostaglandin synthesis Immune cell Recruitment ↑Vascular PermeabilityCompliment System Prostaglandins PGD2 = Bronchoconstriction, anti-platelet PGE2 = Chemotaxis, histamine, inflammation PGF2 = Bronchoconstriction, uterine contraction PGI2 = Antiplatelet aggregation, vasodilation TXA2 = Platelet aggregation, vasoconstrictionInflammationCardinal Signs of Inflammation 5 Cardinal Signs of Inflammation: 1. Heat 2. Redness 3. Pain Heat 4. Swelling (oedema) 5. Loss of function Redness Heat and redness are caused by increased blood supply to the area via vasodilation and increased metabolic activity. Pain (Caused by histamines and cytokines e.g TNF-a) Swelling is caused by increased tissue fluid in the area as well as inflammatory cells such as neutrophils and WBCs. Swelling Increased fluid can also compress nearby nociceptors, Loss of Function eliciting pain sensations in the individual. In addition, the swelling can also impair motor nerve function and this can restrict movement e.g. of a joint, causing loss of function. Question 1 Barry is revising for S1. His friend asks him a very high yield A Tight binding, rolling adhesion, diapedesis, migration question; what are the stages for neutrophils entering the tissue. Barry is upset he can’t remember and turns to you for help. B Rolling adhesion, tight binding, diapedesis, migration What are the order of the steps of cell marginalisation ? C Diapedesis, migration, tight binding, rolling adhesion Rolling adhesion, diapedesis, D migration, tight binding E Tight binding, diapedesis, rolling adhesion, migration Question 1 Barry is revising for S1. His friend asks him a very high yield A Tight binding, rolling adhesion, diapedesis, migration question; what are the stages for neutrophils entering the tissue. Barry is upset he can’t remember and turns to you for help. B Rolling adhesion, tight binding, diapedesis, migration What are the order of the steps of cell marginalisation ? C Diapedesis, migration, tight binding, rolling adhesion Rolling adhesion, diapedesis, D migration, tight binding E Tight binding, diapedesis, rolling adhesion, migration Immune cell Chemotaxis Cell Marginalisation RED TREES DANCE MONTHLY (in MAY) Inflammation Part 1 Part 2 • Pathogens have DAMPs or PAMPs • The neutrophil usually completely clears the infection. It • These are recognised by mast cells which secrete prostaglandin and will undergo apoptosis after it has phagocytosed a histamine • Prostaglandin and histamine causes increased permeability to pathogen. endothelium (Leaky blood vessels) • The macrophage will then phagocytose the apoptotic • Capillaries dilate and clotting begins. neutrophil and release anti-inflammatory cytokines. • Monocytes come into region to secrete cytokines (CXCL8 = attracts • Tissue repair will then occur. neutrophils, TNF-alpha = vasodilation) • Neutrophils carry out phagocytosisWound Healing Stages of Wound Healing (HIPR) 01 Haemostasis 02 Inflammation Primary Haemostasis • Wound Sterilisation Blood Vessel constriction and platelets form • Clearance of debris soft clot around vessel rupture. • Removal of infection and damaged tissues • Neutrophils + Macrophages Secondary Haemostasis • Vascular Permeability Fibrin formation and stabilization of clot 03 Proliferation 04 Remodeling • Repair tissue • Return tissue to normal function • Angiogenesis • Wound Closure • Granulation • Scar Maturation • Fibroblast proliferation • Reorganise new ECM • Collagen synthesis • Remove blood vessels • Early epithelialisation W ound Healing Wound Healing Stages Inflammation Proliferation Remodelling Proliferation & Remodeling Summary Proliferation Remodeling Epithelisation Stem cells in epidermis (basal cells) proliferate to replace damaged/lost cells Fibroblasts reorganise the disordered Fibroplasia Fibroblasts in the dermis proliferate and secrete collagen (fibroplasia) collagen. (ECM) Collagen -> Collagen fibrils -> collagen bundles (supports epidermis) Type 3 Collagen -> Type 1 Angiogenesis Creation of new blood vessel stimulated by collagen formation, VEGF and other Myofibroblasts -> Contraction -> growth factors. wound closure Pericyte detachment -> Tip cell migration -> Regulation of Vessel size Granulation Fibroblasts produce PG, GAG and collagen -> ground substance Granulation tissue is deposited in areas without tissue. Scars Hypertrophic Scars Keloids Rapid growth Constant growth Alpha SMA+ Myofibroblasts Extends beyond margins of tissue Collagen fibres parallel to skin surface Genetic predisposition Vertically orientated blood vessels More likely to Female African Caribbean Thick haphazardly orientated collagen bundles Factors affecting wound healing Intention of wound healing Systemic Local Primary Secondary Nutrition Infection Wound edges brough together Wound contraction Metabolic status Mechanical factors Epithelialisation Healing by granulation Circulatory Status Foreign bodies Minimal scarring Broad scar Hormones Size/Location/type of wound Risk of infectionBones and Disease Haemostasis Inflammation Granulation Bone Healing Callus Formation Consolidation & Remodeling Bone Healing Stages of Bone Healing Haemostasis Inflammation Granulation The blood vessels in the bone burst • Acute inflammation occurs due to • Angiogenesis into the area of the fracture. • Mesenchymal stem cells proliferate and which causes blood to seep out. damage and DAMPs • Inflammatory cells enter i.e differentiate into fibroblast, chondroblasts This forms a hematoma (abnormal and osteoblasts which deposit tissue. macrophages + neutrophils. collection of blood outside blood • The formation of this granulation tissue and vessels) • These inflammatory cells break cartilage is a soft callus that replaces the down red blood cells (clot) blood clot. Remodeling Consolidation Callus Formation Activity of osteoclasts and osteoblasts • Islands of cartilage appear • Excess bone is slowly reabsorbed by continuous reabsorption and replaces the woven bone into laminar • Calcium is deposited into cartilage. • Osteoblasts secrete osteoid. formation. bone. Osteoclasts: Break-down and reabsorb • This causes intramembranous ossification to • Fibres get aligned to allows for occur, and bone connects the bones. bone • Endochondral ossification occurs and bones maximum weight bearing. • Often takes years Osteoblasts: Secrete more osteoid. fully connect. The bony callus is formed. Question 2 A 85-year-old man, has recently picked up the hobby of A Rheumatoid Arthritis painting and enjoys it thoroughly but suffers from pain and stiffness in his hands. He goes to the GP and the doctors orders an X-ray of his hand; the results are shown below. B Osteoarthritis What does the patient most likely have? C Normal X ray D Broken thumb E Osteoporosis Question 2 A 85-year-old man, has recently picked up the hobby of A Rheumatoid Arthritis painting and enjoys it thoroughly but suffers from pain and stiffness in his hands. He goes to the GP and the doctors B Osteoarthritis orders an X-ray of his hand; the results are shown below. What does the patient most likely have? C Normal X ray D Scaphoid Fracture E Osteroperosis Rheumatoid Arthritis Osteoarthritis L - loss of joint space L - loss of joint space E - erosion O - osteophytes S - soft tissue swelling S - subchondral sclerosis S - soft bone (osteopenia) S - subchondral cysts Arthritis Degenerative Inflammatory Osteoarthritis Rheumatoid • Commonly has deformities (Boutonnieres, Swan neck, Ulnar • Unilateral • Affects weight bearing Joints Deviation) • Bilateral • Short morning stiffness • Improves with use • Worsens with use • More common in females • Prolonged morning stiffness Question 3 Jenny, a 75-year-old female comes to the GP for a follow up, A Secondary Osteoporosis after a closed fracture of her femur following a fall in her care home. B Ankylosing Spondylitis When the GP asked her how she has been since the injury, She has recovered well and is otherwise health, but does C Rheumatoid Arthritis mention that she feels like she has shrunk and is shorter than she used. She mentions no relevant past medical history or D Primary Osteoporosis drug history. What does the patient most likely have? E Osteoarthritis Question 3 Jenny, a 75-year-old female comes to the GP for a follow up, A Secondary Osteoporosis after a closed fracture of her femur following a fall in her care home. B Ankylosing Spondylitis When the GP asked her how she has been since the injury, She has recovered well and is otherwise health, but does C Rheumatoid Arthritis mention that she feels like she has shrunk and is shorter than she used. She mentions no relevant past medical history or D Primary Osteoporosis drug history. What does the patient most likely have? E Osteoarthritis Bone & Diseases Osteoporosis Aetiology Treatment Risk Factors Osteoporosis is caused by an imbalance between Primary Prevention → Diagnosed before fracture • Female the number osteoclasts and osteoclasts. Stop smoking and reduced alcohol intake • > 50yrs Increase calcium and vitamin D intake • No children Weight bearing exercises • Slim Osteoclasts>Osteoblasts Secondary Prevention → post-menopause or after fracture • ↑ Alcohol Primary = Post-menopausal/ age related Bisphosphonates, Strontium, SERMS, PTH. consumption Secondary = Drug related/ Co-morbidity Hormone replacement therapy • Smoking Signs & Symptoms Diagnosis “Shorter then they were before” Loss of height X-ray, Bloods, Bone profile, DEXA Scan Kyphosis Hump T score -1 > t < -2.5 = Osteopenia Unsteady/skeletal tenderness T score >-2.5 = Osteoporosis Fragility fractureRadiology of the Lower Limb Question 3/4/5 A 70-year-old woman complaining of chronic back pain comes to the GPAto asArthroplasty (Full Hip Replacement) some painkillers to relieve her pain. In the process of your consultation with her, she mentions that she feels like she was shorter than she used to be and that she has been going to A&E more often than before due to fractures from falls. You think shed Screws may have osteoporosis and send her for a DEXA scan. 2 weeks later, the results come back, and she has a t-score below -2.5 confirming your diagnosiC. ButNSAIDse you have a chance to tell her, she has another fall at home causing her to be rushed to the A&E. Due to her condition an X-ray is taken immediately. WhatDis tHemiarthroplasty treatment? E Dynamic Hip Screw Question 3/4/5 A 70-year-old woman complaining of chronic back pain comes to the GPAto asArthroplasty (Full Hip Replacement) some painkillers to relieve her pain. In the process of your consultation with her, she mentions that she feels like she was shorter than she used to be and that she has been going to A&E more often than before due to fractures from falls. You think shed Screws may have osteoporosis and send her for a DEXA scan. 2 weeks later, the results come back, and she has a t-score below -2.5 confirming your diagnosiC. ButNSAIDse you have a chance to tell her, she has another fall at home causing her to be rushed to the A&E. Due to her condition an X-ray is taken immediately. WhatDis tHemiarthroplasty treatment? E Dynamic Hip Screw Imaging Femoral Fractures Extrascapular Intrascapular Vascular supply to the Intracapsular fractures are at femoral head remains risk of avascular necrosis and therefore conservative displacement of the femoral management needed. head. The medial circumflex arteries can be damaged and Extrascapular fractures can lead to a lack of blood supply be fixed with a dynamic hip to the head. screw as the blood supply of the head is not at risk. Intrascapular fractures can be treated with either a hip screw or hemi arthroplasty (partial replacement of the hip joint) -> hemi-arthroplasty is only used if the neck has moved away from the bone. Question 1 A 54-year-old man presents to the GP with difficulty walking A Talus fracture after falling off his roof. On an X-ray of his foot, this was seen. Cuneiform fracture What can be seen? B C Normal X ray D Cuboid fracture E Navicular fracture Question 1 A 54-year-old man presents to the GP with difficulty walking A Talus fracture after falling off his roof. On an X-ray of his foot, this was seen. What can be seen? Cuneiform fracture B C Normal X ray D Cuboid fracture E Navicular fracture Question 2 On further examination, the doctors decide to conduct an X- A Communited fracture ray of his leg. Weber A fracture What can be seen? B C Weber B fracture D Weber C fracture E Tibial fracture Question 2 On further examination, the doctors decide to conduct an X- A Communited fracture ray of his leg. Weber A fracture What can be seen? B C Weber B fracture D Weber C fracture E Tibial fracture Weber A Weber B Weber C A = Inferior to syndesmosis, stable B = Level of syndesmosis, variable stability C= Above ankle joint, damage to syndesmosis ligament, unstable THANKS FOR WATCHINGPLEASE FILL OUT THE FEEDBACK FORM PLEASE TUNE IN TO OUR REMAINING SESSIONS THIS WEEK