Lec 7 Musculoskeletal Neoplasia and DM PDF

Lec. 7: Metabolic &rheumatic disorders of skeletal system, Neoplasia and Diabetes Mellitus Saturday, 15-11- 2024 Objectives: 1- Studying of different disorders affecting Musculoskeletal Function. 2- Definition, pa...

Lec. 7: Metabolic &rheumatic disorders of skeletal system, Neoplasia and Diabetes Mellitus Saturday, 15-11- 2024 Objectives: 1- Studying of different disorders affecting Musculoskeletal Function. 2- Definition, pathogenesis and types of Neoplasia. 3- Studying of diabetes and its related complications. 1- Metabolic &rheumatic disorders of skeletal system.  For your knowledge During childhood, skeletal structures grow in length and diameter and sustain a large increase in bone mass. Skeletal disorders may develop as a result of abnormal growth and developmental processes due to hereditary or congenital influences. Other skeletal disorders can occur later in life as a result of  Metabolic disorders  Hormonal influences  Aging process  Nutritional deficiencies 3  Osteoporosis and Osteomalacia Osteoporosis is a metabolic bone disease characterized by a loss ofmineralized bone mass causing increased porosity andcauses Osteomalacia susceptibility to fractures soft bones. due to inadequate mineralization of bone (a lack of vitamin D). Osteomalaci Osteoporosis (silent disease) a Osteomalacia (painful disease) Osteoporosi  Etiology of osteoporosis Imbalance between bone resorption and formation. Hormonal factors play a significant role in the development of osteoporosis. E.g. : Postmenopausal osteoporosis, which is caused by an estrogen deficiency. Other risk factors: Age. Gender. Genetic predisposition. Activity level. Nutritional status. Etiology of osteomalacia Vitamin D deficiency is caused Causes of osteomalacia:most commonly by reduced  Calcium deficiency. vitamin D absorption as a result  Phosphate deficiency. of biliary tract or intestinal  Vitamin D deficiency. diseases that impair fat and fat- soluble vitamin absorption and kidney failure.  Diagnosis Diagnostic methods include x-ray studies, laboratory tests, bone scan, and bone biopsy. Osteomalaci Osteoporosi 6  Rickets Rickets is the softening and weakening of bones in children, usually because of vitamin D deficiency. Etiology As with osteomalacia in the adult, rickets can result from kidney failure or malabsorptive syndromes.  Rheumatoid Arthritis  Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease. RA mainly attacks the joints, usually many joints at once.  Women are affected approximately three times more frequently than men. Etiology and Pathogenesis It has been suggested that the disease is initiated in a genetically predisposed person by the activation of a T cell–mediated response to an immunologic trigger, such as a microbial agent. Disease process in rheumatoid arthritis. (1) A virus or some trigger stimulates the synovial cells to proliferate. (2) The lymphocytes, plasma cells, and mast cells, along with neovascularization and edema, leads hyperplasia of the synovium. (3)Lymphoid nodules are present. (4) Proliferating synovium extends into the joint space, burrows into the bone beneath the articular cartilage, and covers the cartilage as a pannus. The articular cartilage is eventually destroyed by direct resorption or 9  Diagnosis and Treatment The diagnosis of RA is based on findings of the history, physical examination, and laboratory tests. Treatment The treatment goals for a person with RA are to 1. prevent and/or reduce the pain 2. Decrease stiffness and swelling 3. Maximize mobility 4. Possibly halt the pathological process Drug treatment: Methotrexate. Steroids. NSAIDs.  Osteoarthritis (OA) OA is a slowly progressive destruction of articular cartilage of weight-bearing joints and fingers of older adults and the joints of younger people who have experienced trauma. Formerly OA called degenerative joint disease, is the most prevalent form of arthritis and is a leading cause of disability and pain in older adults. OA is considered to have an inflammatory component along with the degenerative aspect. 1 1  Epidemiology and Risk Factors of Osteoarthritis  Primary OA affects 4% of people between 18 and 24 years of age; 85% of people with OA are in their seventies. Clinical Manifestations of Osteoarthritis  The manifestations of OA may arise suddenly or insidiously. Initially, pain may be described as aching and may be somewhat difficult to localize. Diagnosis and Treatment of Osteoarthritis  The diagnosis of OA usually is determined by history and physical examination, x-ray studies, and laboratory findings that exclude other diseases. Medications: NSAIDs. Treatment Intermittent hot and cold packs. Physical and exercise therapy. Weight loss. 2 4  Ankylosing Spondylitis Ankylosing spondylitis (AS) is a chronic, systemic inflammatory disease of the joints and ligaments of the vertebral column (spine) manifested by pain and progressive stiffening of the spine. The disease usually evolves more slowly and is less severe in women.  Clinical Manifestations (S/S) of Ankylosing Spondylitis The person with AS typically complains of lower back pain, which may be persistent or intermittent. The pain, which becomes worse when resting, particularly when lying in bed, initially may be attributed to muscle strain or spasm from physical activity. Loss of motion in the spinal column is characteristic of the disease.  GOUT Gout is a group of disorders characterized by increased serum uric acid and urate crystal deposits in kidneys and joints. The majority of people with high serum uric acid are older men. All people diagnosed with a gout disorder have a high uric acid level greater than 6.8 mg/dL, but fewer than 15% of people with high serum uric acid have a gout disorder.  GOUT The pathogenesis of gout resides in an elevation of serum uric acid levels. Uric acid is the end product of purines (adenine and guanine from DNA and RNA) metabolism.  Clinical Manifestations of Gout Gout is categorized into four phases: 1.The asymptomatic hyperuricemia. 2.Acute gout arthritis. 3.Intercritical gout. 4.Chronic tophaceous gout (Advanced gout). Diagnosis Gout can only be diagnosed during a flare when a joint is hot, swollen, and painful and when a lab test finds hyperuricemia and uric acid crystals in the affected joint.  Systemic Lupus Erythematosus SLE is a chronic inflammatory disease that can affect virtually any organ system, including the musculoskeletal system. Etiology and Pathogenesis The cause of SLE is unknown. It is characterized by the formation of autoantibodies and immune complexes. Treatment The medications most commonly used to control lupus include: Nonsteroidal anti-inflammatory drugs. Antimalarial drugs.... Corticosteroids.... Immunosuppressants. 2- Neoplasia  Hyperplasia vs Dysplasia vs Before cancer Metaplasia cells are formed in body's tissues, they go through abnormal changes called hyperplasia and dysplasia.  Cell Proliferation (For your Cell knoledge) proliferation is the process of increasing cell numbers by mitotic cell division. In normal tissue, cell proliferation is regulated so that the number of cells actively dividing is equivalent to the number dying or being shed. The gametes (ovum and sperm) are haploid, having only one set of chromosomes from one parent, and are designed specifi cally for sexual fusion. After fusion, a diploid cell containing both sets of chromosomes is formed. This cell is the somatic cell that goes on to form the rest of the body. Physiology of Cell Proliferation (For your knoledge) In terms of cell proliferation, the 200 various cell types of the body can be divided into three large groups: (1) The well diff erentiated neurons and cells of skeletal and cardiac muscle cells that rarely divide and reproduce. (2)The progenitor or parent cells that continue to divide and reproduce, such as blood cells, skin cells, and liver cells. (3)The undiff erentiated stem cells that can be triggered to enter the cell cycle and produce large numbers of progenitor cells if needed.  Benign  Benign tumors are Neoplasms composed of well-diff erentiated cells that resemble the cells of the tissues of origin and are characterized by a slow progressive rate of growth that may come to a standstill or regress.  They remain localized to their site of origin, lacking the capacity to invade distant sites.  Because they expand slowly, they develop a surrounding rim of compressed connective tissue called a fi brous capsule.  The capsule is responsible for a sharp line of demarcation between thebenign tumor and the a d jacent tissues, a factor that facilitates surgical removal.  Malignant  Malignant Neoplasms neoplasms, which invade and destroy nearby tissue, tend to grow rapidly and spread widely and have the potential to cause death.  Malignant tumors may compress blood vessels and outgrow their blood supply, causing ischemia and tissue injury.  Malignancies secrete hormones or cytokines, liberate enzymes and toxins, or induce an infl ammatory response that injures normal tissue as well as the tumor itself.  Types of malignant There are neoplasms two categories of malignant neoplasms: 1. Solid tumors. 2. Hematologic cancers. Solid tumors initially are confi ned to a specifi c tissue or organ. As the growth of the primary solid tumor progresses, cells detach from the original tumor mass, invade the surrounding tissue, and enter the blood and lymph systems to spread to distant sites, a process termed metastasis. Metasta sis Solid tumors  Hematologic Cancers Also called blood cancer. Cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Examples of hematologic cancer are leukemia, lymphoma, and multiple myeloma. Lymphom Leukemi a a Multiple myeloma  Metastatic cancer. The mesentery attached to a part of the small bowel has small nodules of metastatic ovarian carcinoma attach8 ed.  Cancer Cell Characteristics Cancer cells are characterized by two main features: abnormal and rapid proliferation and loss of differentiation. Loss of differentiation means that they do not exhibit normal features and properties of differentiated cells and hence are more similar to embryonic cells. The term anaplasia describes the loss of cell diff erentiation in cancerous tissue.  Host and Among the Environmental Factors traditional risk factors that have been linked to cancer are:  Heredity  Hormonal factors  Immunologic mechanisms  Environmental agents such as chemicals  Radiation  Cancer-causing viruses. More recently, there has been interest in obesity as a risk factor for cancer.  Alcohol and Smoking Alcohol is associated with a variety of cancers. The fi rst and most toxic metabolite of ethanol is acetaldehyde that can cause point mutations in some cells. The carcinogenic eff ect of cigarette smoke can be enhanced by concomitant consumption of alcohol; people who smoke and drink considerable amounts of alcohol are at increased risk for development of cancer of the oral cavity, larynx, and esophagus.  Anemia Anemia is common in people with various types of cancers. It may be related to:  Blood loss  Hemolysis  Impaired red blood cell production  Treatment eff ects. For example, drugs used in treatment of cancer are cytotoxic and can decrease red blood cell production. Also, there are many mechanisms through which erythrocyte production can be impaired in people with malignancies, including nutritional defi ciencies.  Cancer Treatment The goals of cancer treatment methods fall into three categories:  Curative  Control  Palliative The most common modalities are:  Surgery  Radiation therapy  Chemotherapy  Hormonal therapy  Biotherapy  Adenocarcinoma It develops in the glands that line organs. Common forms of adenocarcinoma include breast, stomach, prostate, lung, pancreatic and colorectal cancers. 5 7  Other Common Cancer Types (For your knowledge) Bladder Cancer Breast Cancer Cervical Cancer Colorectal Cancer Kidney Cancer Liver Cancer Lung C ancer Lymphoma Ovarian Cancer Prostate Cancer Skin Cancer Th yroid Cancer Uterine Cancer Vaginal and Vul var Cancers 5 9  Physiology Introduction (For your Knowledge) Glucose-Regulating Hormones The hormonal control of blood glucose resides largely with the endocrine pancreas. The pancreas is made up of two major tissue types—the acini and the The islets of Langerhans. acini secrete digestive juices into the duodenum, whereas the islets of Langerhans secrete hormones into the blood. Each islet is composed of beta cells that secrete insulin and amylin, alpha cells that secrete glucagon, and a small number of delta cells that Islet of Langerhans in the secrete somatostatin. pancreas 3- Diabetes Mellitus and the Metabolic Syndrome  Insulin Insulin is the only hormone known to have a direct effect in lowering blood glucose levels. The actions of insulin are threefold: 1. It promotes glucose uptake by target cells and provides for glucose storage as glycogen. 2.It prevents fat and glycogen breakdown. 3.It inhibits gluconeogenesis and increases protein synthesis.  Classification of Diabetes Although DM clearly is a disorder of insulin availability, it is not a single disease. Two broad categories of DM are 1- Type 1. 2- Type 2. 3- Gestational diabetes mellitus (GDM) (i.e., diabetes that develops during pregnancy).  Stages of Diabetes The revised classification system also includes a system for diagnosing diabetes according to stages of glucose intolerance.  Type 1 Diabetes Mellitus Type 1 DM is characterized by destruction of the pancreatic beta cells. It is a catabolic disorder characterized by an absolute lack of insulin, an elevation in blood glucose, and a breakdown of body fats and proteins. Type 1 diabetes can be subdivided into two types: Type 1A immune mediated diabetes Type 1B idiopathic (non–immune-related) diabetes. The onset of type 1B is less common and does not seem to have an autoimmune component.  Type 1A Immune-Mediated Diabetes Commonly referred to simply as type 1 diabetes, is characterized by immune- mediated destruction of beta cells.  Type 2 Diabetes Mellitus and the Metabolic Syndrome  Type 2 DM accounts for the majority of cases of diabetes, approximately 90% to 95%.  It is a heterogeneous condition that describes the presence of hyperglycemia in association with relative insulin deficiency.  Autoimmune destruction of the beta cells does not occur.  Although many people with type 2 diabetes are adults and overweight, recent trends indicate type 2 diabetes has become a more common occurrence in obese adolescents and children.  Type 2 Diabetes Mellitus and the Metabolic Syndrome Type 2 diabetes has a strong genetic component. The metabolic abnormalities that lead to type 2 diabetes include: 1.Insulin resistance. 2.Decreased secretion of insulin by the pancreatic beta cells. 3.Increased glucose production by the liver.  Insulin Resistance and the Metabolic Syndrome Metabolic syndrome is a group of five risk factors that can increase the chance of developing heart disease, diabetes, and stroke. The five risk factors include: 1- increased blood pressure (greater than 130/85) 2- high blood sugar levels (insulin resistance) 3- excess fat around the waist 4- high triglyceride levels (Triglycerides >150 mg/dl) 5- low levels of good cholesterol, or HDL Men