Rehab 521 Lecture 28 Osteoporosis & Arthritis PDF

Bone - Soft tissue module: Osteoporosis, Arthritis, Integumentary pathophys Pathophysiology of: Osteoporosis Osteoarthritis/Degenerative joint disease Rheumatoid arthritis Juvenile idiopathic arthritis Integumentary pathophysiology of: ulcers burns Rehab 521: Pathophy...

Bone - Soft tissue module: Osteoporosis, Arthritis, Integumentary pathophys Pathophysiology of: Osteoporosis Osteoarthritis/Degenerative joint disease Rheumatoid arthritis Juvenile idiopathic arthritis Integumentary pathophysiology of: ulcers burns Rehab 521: Pathophysiology Mary Beth Brown, PT, PhD  Remember Metabolic bone disease this slide from previous bone 3 most common endocrine disorder, after diabetes andlecture? rd thyroid disorders Refers to a large spectrum of bone disorders, usually with mineral abnormalities (e.g. calcium, phosphorus, magnesium or vitamin D) The more common ones include – osteoporosis – rickets/osteomalacia – fluorosis – primary hyperparathyroidism (PHPT) The rarer ones include – Paget disease – tumor-induced osteomalacia – fibrous dysplasia – osteogenesis imperfecta  Osteoporosis What is it? A metabolic bone disease characterized by: 1. Excessive osteoclast-mediated bone resorption 2. Compromised bone strength 3. Increased risk of fracture at all skeletal sites 4. Fractures Normal bone from Osteoporotic 22-year old male female in her 80’s  Osteoporosis Loss of height with no significant bone pain is a common presentation – Greater than 2” loss is a predictor of osteoporosis and risk for fracture, with vertebral fracture largely underlying the height loss  Osteoporosis Types 1. Primary – Post-menopausal – Senile 2. Secondary: caused by other conditions Normal bone from Osteoporotic 22-year old male female in her 80’s  Types of osteoporosis Primary – Postmenopausal osteoporosis Associated with ↓estrogen which accelerates the rate of bone remodeling, leading to an increase in the amount of bone being resorbed, with less being replaced Low estrogen levels in males can also ↑ their risk for osteoporosis  Types of osteoporosis Typical pattern of age-related changes in bone mass, which is primarily accrued during the pre- pubertal and adolescent stages, reaches a lifetime peak at approximately 18 years of age, and declines sharply during perimenopause From: Exercise Early and Often: Effects of Physical Activity and Exercise on Women’s and steadily BoneRes. Int. J. Environ. Health Public Health 2018, 15(5), 878;  Types of osteoporosis Primary – Senile osteoporosis Less precursor cells (BMSC) differentiate into bone remodeling cells Process of bone resorption exceeds bone formation, so more bone is being broken down than is being replaced resulting in a net loss  Types of osteoporosis Secondary (caused by other conditions): Hormonal imbalances unrelated to menopause – ↓Estrogen/testosterone due to endocrine disorder As a consequence of other diseases Medications (especially corticosteroids) Eating disorders* (or more broadly, RED-S) For example, renal Spinal cord injuries disease Chronic kidney disease–related Depression osteoporosis is associated with incident frailty among patients with diabetic kidney disease: a propensity score–matched cohort study. Osteoporos Int 31, (2020). https://doi.org/10.1007/s00198-020-05353-9  Types of osteoporosis Secondary (caused by other conditions): Hormonal imbalances unrelated to menopause – ↓Estrogen/testosterone due to endocrine disorder As a consequence of other diseases Medications (especially corticosteroids) Eating disorders* (or more broadly, RED-S) Spinal cord injuries Depression Fracture of an osteoporotic humerus in a patient with SCI From: Osteoporosis and Spinal Cord Injury https://emedicine.medscape.com/article/322204-overvie  Remember this from last module? RED-S: Pathophysiology Results in decreased sports performance due to: Endocrine-derived physiological consequences leading to: increased cortisol, decreased T3, LH and hypoestrogenism Low Energy Availability leads to: increased bone stress injury and impaired training and competition availability Decreased neuromuscular performance associated with lower fat-free mass in the leg, glucose, estrogen, T3, elevated cortisol Thought that there may be some biomarker relationship especially with consistently low blood glucose leading to increased cortisol and reduced T3 with lower muscle mass long term. Low estrogen/testosterone can lead to increased bone resorption and bone loss.  Types of osteoporosis These mechanisms are just FYI, not on exam Secondary (caused by other conditions): Hormonal imbalances unrelated to menopause – ↓Estrogen/testosterone due to endocrine disorder Certain diseases Medications (corticosteroids, glucocorticoids) Eating disorders Spinal cord injuries ‘Depression as a risk factor for osteoporosis’ Trends in Endocrinology and Metabolism 2009  Clinical assessment of bone mass Dual-energy x-ray absorptiometry (DXA) scan: provides a T-score which is the patient’s bone density compared to a healthy young adult (~30 years old)  Example of DXA scan You will NOT be expected on results exam to know how to read a DXA report Normal bone: T-score higher than - 1 Osteopenia: T-score between -1 Risk factors for osteoporosis Age: >50 years – Peak bone mass ~30 years of age Biological sex: Females > males Non- Race: Caucasian, Asian modifiab Body habitus: Thin le risk Family history: Osteoporosis and factors fracture Lifestyle: Long periods of inactivity or Modifiab immobilization, cigarette smoking, alcohol intake, medications such as le risk corticosteroids factors Diet: Lack of calcium and vitamin D  Pathophysiology of osteoporosis Early Inadequat menopausal e peak Low bone loss bone bone mass mass/ impaired Calcium/ Decrease bone in bone quality Fractures vitamin D deficiency mass/bon e quality Other Trauma factors  Pathogenesis of bone loss due to calcium and vitamin D deficiency Impaired renal Estrogen function deficiency Decreased calcium absorption Decreased Low dietary vitamin D Secondary Calcium intake synthesis hyperparathyroidis m Remember that PTH increases osteoclast Decreased sunlight activity to increase exposure bone resorption Bone Loss  Factors associated with fractures Risks for Fracture in a Fall Failure to break a fall Falling to the side/from height Low bone mass Unfavorable bone geometry High bone turnover, resorption pits  Skeletal response to disuse Bone loss occurs during disuse – Examples: spaceflight, prolonged immobilization/bed rest, casting, spinal cord injury  Skeletal response to disuse Bone loss occurs during disuse – Examples: spaceflight, prolonged immobilization/bed rest, casting, spinal cord injury Astronauts lose an average of more than 1% bone mass per month spent in space Bone adaptation to exercise Unilateral Humeral Hypertrophy in Elite Tennis Players  Osteocyte network Recall this slide from Mechanical bone intro loading lecture? applied at the whole bone level is transmitted through the bone tissue to the cellular level and causes movement of the interstitial The osteocytes are fluid distributed throughout surrounding bone tissue and connect to osteocytes in each other and to bone- the lining cells and osteoblasts mineralized on the bone surfaces. matrix. Figure adapted from Rubin  Bone adaptation to exercise Exercise evokes You don’t need to a multifaceted memorize this signaling signaling pathway, end result is altered osteoclast/blast activity to favor ↑ bone formation and 2019 remodeling https://doi.org/10.11 55/2019/8171897 The Effect of Exercise on the Prevention of Osteoporosi s and Bone Angiogenesi  Osteoporosis prevention Currently no cure, prevention is #1 priority to prevent fractures Strategies to maximize bone mass to reduce fractures: – Maximize peak bone mass – Weight-bearing physical activity To increase bone mass and reduce falls – Adequate Be as high as of calcium and vitamin amounts – Normal possible on that cycles menstrual – rollercoaster Adequate bodyride weight – May up,require beforedrug the therapy (example: PTH, bisphosphonates) inevitable plummet down!  Osteoporosis prevention Currently no cure, prevention is #1 priority to prevent fractures Strategies to maximize bone mass to reduce fractures: – Maximize peak bone mass – Weight-bearing physical activity To increase bone mass and reduce falls – Adequate amounts of calcium and vitamin D – Normal menstrual cycles – Adequate body weight – May require drug therapy (example: PTH, bisphosphonates)  Osteoporosis prevention – May require drug therapy (example: PTH, bisphosphonates) Bisphosphonates MOA: bind to hydroxyapatite crystals on bony surfaces, and inhibit osteoclast-mediated bone resorption https://www.researchgate.net/publication/44643481_Risks_and_benefits_of_long-term_bisphospho nate_therapy  This is just FYI, if How is risk for osteoporosis for transgender interested individuals? The gist of this figure in terms of clinical significance is that careful managing of exogenous hormones is critically important in medical management of cisgender- transgender transition for reasons related to bone health, too. This is because, as the figure indicates, the relative role of the sex hormoneshttps://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30353-5 in maintaining bone t  Bone - Soft tissue module: Osteoporosis, Arthritis, Integumentary pathophys Pathophysiology of: Osteoporosis Osteoarthritis/Degenerative joint disease Rheumatoid arthritis Juvenile idiopathic arthritis Integumentary pathophysiology of: ulcers burns Rehab 521: Pathophysiology Mary Beth Brown, PT, PhD Osteoarthritis (OA)  Osteoarthritis (OA) Articular disease that originates in cartilage – OA is also referred to as ‘wear and tear arthritis’, degenerative joint disease (DJD), degenerative arthritis – OA impacts bone, soft tissues and synovial fluid  Osteoarthritis: Tissue Changes Healthy Joint Tissue Osteoarthritic Joint Tissue Loss of articular cartilage, smooth Smooth articular surface of femoral is rough with nodular overgrowth condyle. Smooth surface minimize of bone. There is less cartilage to friction between the bone ends of a attenuate mechanical loads, with joint joint pain increasing with disease progression  Incidence of Osteoarthritis Most common form of joint disease in the US – Number of new cases continue to increase as the population ages Prevalence in the elderly is comparable to heart disease Typically >45 yrs of age, with females > males Joints most affected: hands, low back, and weight-bearing joints of the hip and knee  Osteoarthritis (OA) Classifications – Primary Unknown cause – Intrinsic defect in the articular cartilage – Secondary Known underlying cause – Possible causes: trauma, infection, hemarthrosis, osteonecrosis – May arise from congenital or acquired defects  Etiology and Risk Factors of OA Multifactorial with Smoking both Estrogen Genetics genetic/physiologi cal and environmental factors OA Mechanic Nutritio al factors n Note: included in this is Immun Immobilization- it can e also place the articular Obesity respon cartilage at risk of se degeneration  Exercise and risk for OA Walking and moderate intensity running have been associated with only minimal risk of OA Activities associated with abnormal movements patterns, twisting, high-impact loading, and impact with contact sports increase the risk of OA Limb morphology and abnormal joint biomechanics is an important consideration, particularly when a limb is mechanically loaded Single (acute impact event) or repetitive (cumulative contact stress) Adequate muscle function to prevent joint damage  Contribution of inflammation to OA Inflammation has been implicated in the early progression of OA Higher levels of C- e.g. CRP, TNF-a reactive protein are associated with disease progression, and provide information on the likelihood that a patient’s OA will progress Contribution of inflammation to OA Plasma marker levels and body composition measurements in individuals with knee osteoarthritis (KOA) compared with control subjects. ‘Pro-Inflammatory Biomarkers Combined with Body Composition Display a Strong Association with Knee Osteoarthritis in a Community-Based Biomolecules. Study’ 2023 SeptPMID: 37759715  Contribution of inflammation to OA Synovium of joints from patients with OA stain positive for the inflammatory cytokines like TNF-alpha, markers of inflammation Nitric oxide (NO), released with inflammation, stimulates chondrocyte apoptosis, resulting in degradation of cartilage  Remember this from earlier this quarter? Causes and consequences of low- grade systemic chronic inflammation Nature Medicine vol 25 (2019) https://www.na ture.com/articl es/s41591-019 -0675-0 Common Systemic consequenc chronic es inflammati Commo on n triggers Osteoarthr itis should be included here too!  Osteoarthritis: Pathophysiology 1. Loss of proteoglycans from articular surface, chondrocyte cell death At this point, osteoarthritis progression may stop for a long period of time 2. Fibrillation: the development of surface cracks parallel to the long axis of articular surface 3. Propagation of surface cracks that will allow synovial fluid to move in to the defects (cracks) Refer to handout  Osteoarthritis: Pathophysiology 4. As cracks continue to propagate, neovascularization from epiphysis and subchondral bone will extend into area of crack – This is a problem b/c it allows subchondral osteoclastic bone resorption to occur See – Osteoblastic activity will also imag increase, causes subchondral bone to es thicken in the region where cracks next develop – Normal articular hyaline cartilage is slide replaced with formation of fibrocartilage the fibrocartilage plug is not a permanent fix, it can be worn away, is not mechanically stable Refer to handout  Osteoarthritis: Pathophysiology  Osteoarthritis: Pathophysiology 5. Subchondral bone becomes exposed- now opposite joint surfaces can come into contact with each other Exposed subchondral bone is called: Eburnated bone 6. When eburnated bone tissue cracks, See synovial fluid extends into the imag subchondral bone marrow to form es cysts next slide 7. Osteophytes (bone spurs) will develop, bone nodules on periphery of joint surface These nodules may have different names depending on location (example- interphanlangeal joint ones) Refer to handout  Osteoarthritis: Pathophysiology  Osteoarthritis: Histological Changes * ** Femoral head with osteoarthritis Section through the articular surface shows fibrocartilaginous plugs of an osteoarthritic joint shows focal extending from the marrow onto the absence of articular cartilage, joint surface. Eburnated bone is thickening of subchondral bone*, present over the remaining surface and subchondral bone cyst**  Osteoarthritis: Radiological findings Cartilage loss with narrowing of interphalangeal joints B: Bouchard nodes (osteophytes proximal interphalangeal joints) H: Heberden nodes (osteophytes distal  Osteoarthritis: Diagnosis Common features: – narrowing of joint spaces from loss of articular cartilage – subchondral sclerosis (thickening of subchondral bone) – cyst formation – osteophytes Not all patients that have joint damage will complain of pain – Cartilage itself is not innervated  Osteoarthritis: Diagnosis A diagnosis is based on the following: – Imaging – Health history – Lab work – Physical examination Radiographic findings – Joint space widening (early) – Subchondral bone sclerosis – Subchondral bone cysts – Osteophytes – Joint space narrowing Osteoarthritis: Radiological Findings Osteophyt es Narrow joint space Sclerosis  Osteoarthritis: Osteophytes of the knee Black arrows point to subchondral sclerosis White arrow points to osteophytes Black arrowheads point to joint narrowing Medial compartment  Osteonecrosis and Osteoarthritis Osteonecrosis is also referred to as avascular necrosis, aseptic necrosis It is death of bone and marrow in the absence of infection Case of spontaneous osteonecrosis Osteonecrosis secondary to osteoarthrit Kellgren and Lawrence Grading System for OA Grade 1 – Possible osteophytes; no joint space narrowing Grade 2 – Definite osteophytes; possible narrowing of joint space Grade 3 – Moderate multiple osteophytes; definite joint space narrowing; some sclerosis and possible deformity of bone end. Grade 4 – Large osteophytes; marked joint space narrowing; sever sclerosis and definite deforming of bone ends. You don’t need to memorize this, just know that it is presence and size of osteophytes and extent of joint space narrowing that largely determines OA severity Kellgren and Lawrence Grading System for OA You don’t need to memorize this, just know that it is presence and size of osteophytes and extent of joint space narrowing that largely determines OA severity  Osteoarthritis: Diagnosis Hard tissue enlargement- as disease advances this is more apparent Tissue swelling- during periods of acute exacerbations – The swelling is typically minimal and confined to the joint  Osteoarthritis: Clinical presentation Often deep, achy joint pain that can intensify with activity and use of the involved joint – Pain is more likely to be associated with mechanical loading Periods of stiffness, esp in the am’s and during periods where joint not being actively used In advanced OA, joint motion may become limited Poor correlation between radiographic changes and symptoms/pain – Don’t assume a patient with minimal evidence of joint damage is not in pain  Osteoarthritis: Clinical presentation Crepitus (audible crackling or grating sensation produced when roughened articular or extraarticular surfaces rub together during movement) Enlarged joint surfaces Osteophytes may be palpable Often occurs again in lifetime another joint Arthroplasty ‘frequent flyers’  Rheumatoid Arthritis Rheumatoid Arthritis: 2nd most common form of arthritis after OA Important to be able to distinguish between osteoarthritis and rheumatoid arthritis Rheumatoid Arthritis  Rheumatoid Arthritis Systemic autoimmune disorder that affects the joints and connective tissues throughout the body – Can impact multiple systems inc. blood vessels, heart, lungs Increased risk of C-V morbidity and mortality Disease involves both remissions & exacerbations Individuals with RA have a higher risk of severe infection Articular (this is the joint capsule) and extra- articular (elsewhere throughout the body) presentation ~80% of patients with RA are positive for rheumatoid factor Population most impacted: young - middle age females Joints most impacted: small joints of hands & feet  Rheumatoid Arthritis: Risk Factors Exact cause unknown, definitely a combination of genetic and Chronic inflammation in the etiology of disease across environmental factors the life span – Not all patients with RA present with known genetic markers Any chronic inflammatory condition that increases circulating cytokines Exposure to infectious agents Thyroid disease: Patients with Nature Medicine vol 25 Graves disease or Hashimoto (2019) thyroiditis often have RA Smoking  Rheumatoid Arthritis: Pathophysiology Big picture: RA involves several inflammatory cascades, all lead towards a final common pathway of persistent synovial inflammation and associated damage to articular cartilage and underlying bone RA starts by attacking the joint in the synovium – Healthy synovial membrane contains loose connective tissue, blood vessels and is covered by a layer of synovial lining that consists of macrophages and synoviocytes which a limited number of lymphocytes – In RA, cells of the synovial membrane start to multiply, there is an increase in inflammatory cells and the synovium becomes edematous The synovial lining becomes thicker: clinical synovitis  Rheumatoid Arthritis: Pathophysiology Signaling evoked by auto- antibodie s activates macropha ges to produce pro- inflammat ory products The Lancet, SEMINAR- VOL 376, 2010 Rheumatoid arthritis Anti-cyclic citrullinated peptide or DOI: https://doi.org/10.1016/S0140-6736(10)608 antigen (ACPA) is an antibody present in  Rheumatoid Arthritis: Pathophysiology Signaling evoked by auto- antibodie s activates macropha ges to produce pro- inflammat ory products The Lancet, SEMINAR- VOL 376, 2010 Rheumatoid arthritis Anti-cyclic citrullinated peptide or DOI: https://doi.org/10.1016/S0140-6736(10)608 antigen (ACPA) is an antibody present in  Rheumatoid Arthritis: Pathophysiology Don’t need to memorize criteria, just know that they exist Conventional classification criteria for RA  Rheumatoid Arthritis: Pathophysiology Hypervascularity, ↑ fibrin into the joint space – small fibrin nodules can form in the joint (aka A pannus is rice bodies) formed: destructive vascular granulation tissue – inflammation of the synovium that contains mast cells – covers articular cartilage and isolates it from synovial fluid – invades subchondral bone, sometimes tendons/ligaments  Rheumatoid Arthritis: Pathophysiology Inflammatory cytokines play a https://www.youtube.com/watch?v=Lzp key role in RA 7TIcxuI8 progression – TNF-alpha and IL-6 (responsible for stimulating inflammatory response, factors that can degrade joint) – TNF-alpha also responsible for altering process of bone formation and resorption  Rheumatoid Arthritis: Imaging Disease will progress to significant joint damage – Fibrous fusion of the joint, ‘ankylosis’ – When a bony bridge is formed across a joint ‘bony ankylosis’ – ↓joint ROM  Rheumatoid Arthritis: Progressive Changes in a Metacarpophalangeal Joint (A) soft-tissue swelling, but with intact underlying cortex and no erosions. This is followed by (B) thinning of the radial side of the cortex with minimal disturbance of underlying trabeculae and minimal joint space narrowing. A marginal erosion (C) appears on the radial aspect of the metacarpal head. There is loss of bone substance and joint space Rheumatoid Arthritis: Progressive Joint Changes Serial radiographs taken at four-year intervals show progressive joint damage in this woman with rheumatoid arthritis. Note worsening carpal bone ankylosis, joint space loss and metacarpophalangeal erosions.  RA: Systemic Complications RA is not just limited to joints Rheumatoid nodules: found in extra-articular locations – This are formed of fibrin and degraded collagen – This are movable, firm, rubbery and may be tender to the tough – Can be removed by surgery, but typically will re-appear – Location: areas of pressure, trauma – Have the potential to ulcerate  RA: Systemic complications Rheumatoid nodules have the potential to ulcerate, increasing chance of infection (and increased pain)  RA: Clinical Presentation RA can be difficult to diagnose—particularly early on – Symptoms may come and go – May be mistaken for other diagnoses Characteristics: – Multiple joints involved – Rheumatoid nodules – RF (rheumatoid factor)—autoantibodies that react with immunoglobulin antibodies found in the blood – Anti-cyclic citrullinated peptide (ACPA) is an antibody present in most rheumatoid arthritis patients – Radiographic features of the disease  RA: Clinical Presentation Pain and swelling at joint— the pannus prevents the synovium from performing its 2 main functions: lubricating joint and providing nutrients to the avascular articular cartilage Stiffness with less ability to grip Overall fatigue, sometimes flu-like symptoms Wide spectrum of severity  Rheumatoid Arthritis: Lab Values Synovial fluid has high white blood cell count and low viscosity (can be assessed with arthrocentesis) Erythrocyte sedimentation rate (ESR) is increased in the presence of an inflammatory process (does not specifically indicate RA) Rheumatoid factor (RF) is usually present, but not specific or diagnostic for RA C-reactive protein: indicator of inflammation and a strong predictor of disease outcome in RA Anti-citrullinated protein antibodies (ACPA) is usually present in RA Juvenile Idiopathic Arthritis (JIA)  Juvenile Idiopathic Arthritis (formerly called juvenile RA) Group of arthritides of unknown cause that begin before the age of 16 years ~30,000 to 50,000 children in US are affected The etiology is largely unknown: environmental triggers, viral or bacterial infections, genetic predisposition Fun fact #1: the plural of arthritis is ‘arthritides’ Fun fact #2: the plural of Lego is  Juvenile Idiopathic Arthritis (formerly called juvenile RA) Types: – Pauciarticular JIA – Polyarthritis JIA – Systemic-onset JIA – Psoriatic JIA – Enthesitis-related JIA Type is based on number of joints involved and systemic signs and symptoms  Pauciarticular JIA (Most common) Impacts few (boys, ages of 1-5 yrs Mild presentation with few extra-articular features May have swollen joint, limp, or abnormal gait May have limb length  Diagnosing JIA Family hx, number of joints involved Imaging Lab tests: ESR, anti-nuclear antibody test, CBC, RF, anti-cyclic citrullinated peptide antibodies Arthrocentesis: testing synovial fluid Synovial biopsy: removal of synovial tissue to determine cause of inflammation and synovial damage Pain may be mistaken for growing pain (often found at night) – Pain is typically dull and aching with pain more in the morning/early part of day…ask patient when they notice the pain  Clinical Features of JIA Joint paint, stiffness and swelling More severe in the morning and following naps Loss of joint function Limp, due to pain in lower extremities May have skin rash Myalgia Weight loss Growth problems of the affected limb/joint Secondary complication: low bone mass  Clinical features for JIA 48-year-old woman with polyarticular- onset JRA at age two developed severe hand deformities. These included overgrowth of the epiphyses of the distal radius and ulna; fusion and underdevelopment of the carpal bones; epiphyseal overgrowth at the metacarpophalangeal and interphalangeal joints; resorption at the second to fifth metacarpophalangeal joints bilaterally; and fusion of multiple  Bone - Soft tissue module: Osteoporosis, Arthritis, Integumentary pathophys Pathophysiology of: Osteoporosis Osteoarthritis/Degenerative joint disease Rheumatoid arthritis Juvenile idiopathic arthritis Integumentary pathophysiology of: ulcers burns Rehab 521: Pathophysiology Mary Beth Brown, PT, PhD  Integumentary pathologies Burns Ulcers  Burns Published: 13 Feb 2020 ‘Burn injury’ Nature Reviews Disease Primers, vol 6, Article number: 11 https://www.nature.com/a rticles/s41572-020-0145- (2020) 5 deep partial- thickness burn full-thickness burn  Burns Note the similarly- describe d phases of healing as we have already learned https://www.nature.com/article Published: 13 February 2020 ‘Burn injury’ s/s41572-020-0145-5 Nature Reviews Disease Primers, vol 6, Article number:  Burn pathology Burn size is determined by one of two techniques: the rule of nines (Fig. 10-24) and the Lund-Browder method (Figs. 10- 25 and 10-26)  Burn pathology Burn size is determined by one of two techniques: the rule of nines (Fig. 10-24) and the Lund-Browder method (Figs. 10- 25 and 10-26)  Burn pathology Pain often severe, related to burn size/depth – full-thickness: nerve endings have been destroyed – superficial and partial-thickness: intact and exposed nerve endings – excised eschar (dead tissue) and donor sites expose nerve fibers causing pain – regeneration of periph nerves causes pain – burn injuries are often a combination of above  Burn pathology Recovery phases depend in large part on what is happening with capillary permeability in injured tissue and resultant fluid shifts Fluid is lost from the circulation into burned tissue mainly due to increase in capillary permeability to fluid and macromolecules - “capillary leak”- can lead to serious hemodynamic and  Burn pathology Infection- a common and life- threatening complication Multiple organ system response to burn injury may result in the multiple organ dysfunction syndrome and death (see next slide) Published: 13 February 2020 ‘Burn injury’ Nature Reviews Disease Primers, vol 6, Article https://www.nature.com/article s/s41572-020-0145-5 number: 11 (2020)  Burn pathology You don’t need to memorize this, it is provided as a nice overview of the multiorgan system response to burns that can lead to multiorgan dysfunction, Published: sepsis and 13 February 2020 death ‘Burn injury’ Nature Reviews Disease Primers, vol 6, Article https://www.nature.com/article s/s41572-020-0145-5 number: 11 (2020)  Burn pathology Hypertrophic scarring- complication associated with morbidity and potential lifelong disfigurement – Children and African Americans at greatest risk due to ↑ collagen abundance ‘Hypertrophic scarring: the greatest unmet challenge after burn injury’ October 2016 The Lancet 388(10052):1427-1436 Hypertrophic scar (a) and Keloid (b) that developed following severe burn injuries  Ulcer pathology Pressure ulcers- caused by unrelieved pressure, damaging skin, muscle, and underlying tissue, usually over bony prominences Common risk factors – (1) friction (rubbing/mechanical stress of the skin against another surface) – (2) maceration (softening caused by excessive moisture) – (3) decreased skin resilience (e.g., dehydration) – (4) malnutrition – (5) decreased circulation  Ulcer pathology Pathogenesis: Ischemia and tissue necrosis due to compression & shearing – Compression of capillaries- occludes blood flow in soft tissues between bony prominences and hard or unyielding surfaces - reduces blood supply and lymphatic drainage – Shearing (when the skin layers move in opposite directions)- contributes to ripping/tearing of blood vessels, further damaging tissue  Ulcer pathology Pathogenesis: Ischemia and tissue necrosis due to compression & shearing – If pressure relieved, reactive hyperemia occurs: a brief period of rebound capillary dilation which helps prevent tissue damage PORH: Post occlusion reactive  Ulcer pathology Pathogenesis: Ischemia and tissue necrosis due to compression & shearing – If pressure not relieved, endothelial cells lining capillaries get disrupted by platelet aggregation, microthrombi form that occlude blood flow and cause anoxic necrosis of surrounding tissues  Ulcer pathology Pathogenesis: Ischemia and tissue necrosis due to compression & shearing – Necrotic tissue predisposes to bacterial invasion and subsequent infection, preventing healthy granulation Fig 10-34 necrotic trochanteric pressure ulcer  Ulcer pathology Muscle and tendon tissue can’t tolerate as much pressure loading Tendon and muscle before suffer ischemic incurring damage first that might not be obvious ischemic at the skin surface! damage Fig. 10-33:  Ulcer pathology Repeated application of pressure at pressure- prone regions evoke tissue changes that make them even more susceptible to ulceration  Ulcer pathology Staging of pressure ulcers Skin intact (I) to partial thickness skin loss (II) to full thickness skin loss (III) to necrotic tissue (IV)  Ulcer pathology Pressure can contribute to other types of ulcers (e.g., arterial, venous, neuropathic) Underlying causes of the other types of ulcers can contribute to pressure ulcers developing (see Table 12-20) Example: neuropathic ulcers in diabetes: primary pathogenesis is the absence of protective sensation combined with high pressure… Absence of protective sensation indicates a high risk for pressure ulcers on the feet and heels; diabetic ulcers are typically  Ulcer pathology Necrotic tissue itself is not painful, but surrounding tissue can be painful if intact sensation Tissue trauma can produce an acute inflammatory response with hyperemia, fever, and increased white blood cell count Management can be complicated: Many individuals do not initiate a significant acute inflammatory response – If heavy bioburden from large amounts of necrotic tissue – If immunosuppressed or with diabetes mellitus – Consequence: can’t initiate good healing cascade, are at greater risk for infection – Can instead develop an unresolved chronic inflammation