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PATHO FINAL DISODERS DISEASES STUDY NOTES
Chapter 2 ● HPV HPV types 16 and 18 are strongly associated with cervical cancer, and to a lesser extent, types 31, 33, 35, and 51, with an incident rate of approximately 85%. Additionally, at least 20% of oropharyngeal cancers are associated with high-risk HPV. Cervical cancer can be viewed as a sexually transmitted disease, caused by the transmission of HPV. As such, vaccines were developed and are now offered to protect against these specific subtypes in both young men and women. ● EBV herpesvirus that primarily targets B cells , has been noted to play a role in the pathogenesis of four human cancers: Burkitt lymphoma, nasopharyngeal cancer, B-cell lymphomas in immunosuppressed people, and in some cases of Hodgkin lymphoma. Under normal, healthy circumstances EBV-driven B cell proliferation is quickly controlled. Although an infected individual may experience infectious mononucleosis (mono), they will usually recover without any further complications. However, in regions of the world where Burkitt lymphoma (impairments in B cells) is pervasive, having malaria or another infection simultaneously can cause further impaired immune function, and sustained B-lymphocyte proliferation. ● HHV-8 is associated with Kaposi sarcoma (KS) and is in the same family of viruses as EBV. Kaposi sarcoma is a malignancy that
develops from the endothelial cells that line small blood vessels throughout the body, causing small patches of abnormal skin to develop. KS most frequently occurs in people who are immunosuppressed. In fact, KS was one of the first opportunistic cancers associated with AIDS and is still the most frequent malignancy related to HIV infection. ● HBV is the causative agent in the development of hepatitis B, whereby ~15-25% of infected individuals progress into chronic liver damage, cirrhosis, and ultimately liver cancer (hepatocellular carcinoma). Roughly 70-85% of hepatocellular cancers worldwide are due to infection with HBV or by the closely-related variant hepatitis C (HCV). While the exact mechanism is unknown, the occurrence of cancer is likely the result of prolonged HBV-induced liver damage and regeneration. ● Benign neoplasms are well-differentiated cells, resemble the cells of tissues of origin, and have a slow, progressive rate of growth. They grow by expansion and remain localized to their site of origin, not capable of metastasizing. They develop a rim of connective tissue around the tumor called a fibrous capsule, which aids in surgical removal. Benign tumors are less of a threat unless they interfere with vital functions. ● Malignant neoplasms invade and destroy tissue. They grow rapidly, spread to other parts of the body, often via the circulatory or
○ Adenoma is a benign tumor of glandular epithelial tissues. ○ Osteoma is a benign tumor of bone tissue. ○ Papilloma is a benign finger-like projection that grows on any surface. ○ Carcinoma is a malignant tumor of epithelial tissue origin. ○ Adenocarcinoma is a malignant tumor of glandular epithelial tissues ○ Sarcoma is a malignant tumor of mesenchymal (multipotent) origin. Tissue Type Benign Tumors Malignant Tumors Epithelial: Surface Papilloma Squamous cell carcinoma Epithelial: Glandular Adenoma Adenocarcinoma Connective: Fibrous Fibroma Fibrosarcoma Connective: Adipose Lipoma Liposarcoma Muscle: Smooth Leiomyoma Leiomyosarcoma Neural: Nerve cell Neuroma Neuroblastoma Neural: Glial cell Glioma Glioblastoma/ astrocytoma Hematologic: Granulocytic Myelocytic leukemia Hematologic: Lymphocytic Lymphocytic leukemia/ lymphoma Endothelial: Blood vessels Hemangioma Hemangiosarcoma
CHAPTER 3: IMMUNE SYSTEM DISORDERS
● Type I hypersensitivity reactions are IgE-mediated reactions that develop quickly upon exposure to an antigen. As this is the classic allergic response, the antigens are known as allergens. Common allergens include pollen proteins, foods, house dust mites, animal dander, household chemicals, and even pharmaceutical agents, like penicillin. Exposure can be through inhalation, ingestion, injection, or skin contact and can cause a localized or systemic reaction. Type I reactions include seasonal rhinitis, asthma, and in severe cases, anaphylaxis. ● Anaphylaxis is a systemic life-threatening IgE-mediated hypersensitivity reaction. It is caused by the wide spread release of histamine that produces vasodilation, hypotension, arterial hypoxia, and airway edema. The presence of any amount of allergen introduced into the airway, skin, blood, or GI mucosa can trigger it. ○ Grade I reactions occur in the cutaneous and mucosal tissues with erythema and urticaria, with or without angioedema. ○ Grade II reactions have multisystem involvement with hypotension, tachycardia, dyspnea, and GI manifestations such as nausea, vomiting, diarrhea, and abdominal cramping from mucosal edema. ○ Grade III reactions are life threatening due to bronchospasm,
● Autoimmune diseases occur when the body’s immune system fails to differentiate self from non-self and mounts an immunologic response against host tissues.The detection of autoantibodies can be done by three methods, each relying on the specificity of the antibodies directed towards a specific antigen: indirect fluorescent antibody assay (IFA), enzyme-linked immunosorbent assay (ELISA), or particle agglutination of some kind. Treatment of autoimmune disorders depends on the presenting symptoms and disease process. However, as the exact underlying mechanism is not always known, treatment may be based heavily on addressing the most prevalent symptoms. Corticosteroids and immunosuppressive drugs are the main therapies aimed to stop or reverse cellular damage. In severe cases, plasmapheresis is used to remove autoreactive cells from the circulation. ○ Systemic: Mixed connective tissue disease, Polymyositis-dermatomyositis, Rheumatoid arthritis, Scleroderma, Sjogren syndrome, Systemic lupus erythematosus ○ Blood: Autoimmune hemolytic anemia, Autoimmune neutropenia and lymphopenia, Idiopathic thrombocytopenic purpura ○ Other Organs: Acute idiopathic polyneuritis, Atrophic gastritis and pernicious anemia, Autoimmune adrenalitis, Goodpasture syndrome, Hashimoto thyroiditis, Type 1 diabetes mellitus, Myasthenia gravis, Premature gonadal (ovarian) failure, Primary biliary cirrhosis, Sympathetic ophthalmia, Temporal arteritis, Thyrotoxicosis (Graves disease), Crohn disease, ulcerative colitis ● Systemic lupus erythematosus (SLE) is a chronic inflammatory disease
termed the great imitator because it can affect almost any organ system. It affects predominantly women during their childbearing years. There are four types of lupus, but the most common is SLE. Currently, the precise cause is unknown. It is characterized by the presence of antinuclear antibodies (autoantibodies) and non-self- antigens. The development of autoantibodies can result from a combination of genetic, environmental, hormonal, and immunologic factors. Possible environmental triggers include UV light, chemicals (drugs, hair dyes), some foods, and infectious agents. SLE can affect a multitude of areas both large and small, and includes the musculoskeletal and cardiovascular systems, skin, kidneys, lungs, CNS, red blood cells, and platelets. Clinical symptoms include arthralgias and arthritis, a classic “butterfly” rash, renal disease, pleural effusions or pleuritis, pericarditis, and hematologic problems among others. Diagnosis is made using the criteria from the American College of Rheumatology. The most common laboratory tests are ANA levels (nonspecific, but results will be elevated) and anti-DNA antibody test (more specific). Treatment is geared toward managing the acute and chronic symptoms of the disease, as well as preventing organ damage and long-term complications. NSAIDS control fever and arthritis while antimalarial drugs treat cutaneous and musculoskeletal manifestations. Corticosteroids treat more significant symptoms, such as renal and CNS disorders and immunosuppressive drugs may even be used in more severe cases.
purulent exudate that may be surrounded by a neutrophil layer. Since antibiotics cannot penetrate the abscess wall, surgical incision and drainage may be necessary to cure. ○ ulceration is an epithelial surface that has become necrotic and eroded. It may be caused by traumatic injury to the epithelium (peptic ulcer) or because of vascular compromise (diabetic foot ulcer). ○ vascular phase causes changes in the arterioles, capillaries, and venules at the site of injury. ○ cellular phase delivers leukocytes, predominately neutrophils, to the site of injury to initiate their immune response. ● chronic inflammation lasts from days to years and is often associated with tissue necrosis, the proliferation of blood vessels, the presence of lymphocytes and macrophages, and fibrosis. may result from recurrent or progressive acute inflammatory processes or from low- grade responses that fail to evoke an acute response.This can result in scarring and deformity. ○ Nonspecific chronic inflammation includes an accumulation of macrophages and lymphocytes at the site of injury. They accumulate due to ongoing chemotaxis. This leads to fibroblast proliferation and subsequent scar formation. ○ granulomatous lesion is termed a granuloma , which is typically a 1-2 mm lesion. It consists of macrophages encompassed by
lymphocytes, and is often associated with foreign bodies such as splinters, asbestos, sutures, and silica. It is also seen with microorganisms that cause tuberculosis, deep fungal infections, sarcoidosis, syphilis, and brucellosis. As these agents are poorly digested, they are not easily controlled by other inflammatory mechanisms. ● Keloids are tumor-like masses caused by excess production of scar tissue.abnormality in healing by scar tissue. ● Acquired immunodeficiency syndrome (AIDS) is a disease caused by infection with the human immunodeficiency virus (HIV). It is characterized by extreme immunosuppression associated with opportunistic infections, malignancies, wasting, and central nervous system (CNS) degeneration. HIV carries its genetic information in RNA, and is therefore classified as a retrovirus. A retrovirus must first convert its RNA into DNA before it can be inserted into the host cells genome. AIDS illness, occurs when the CD4+ cell count falls to less than 200 cells/μL or when an individual exhibits an AIDS-defining illness. The best diagnostic method to detect HIV is the HIV antibody test, known as the enzyme immunoassay (EIA) , or the enzyme-linked immunosorbent assay (ELISA). If this test is positive, it is followed by the confirmatory test, the Western blot assay. Polymerase chain reaction (PCR) is used to amplify and detect the presence of trace amounts of viral DNA in infected cells. As such it is especially helpful in diagnosing
severity of the anemia It can be caused by the following: (1) Excessive loss - blood loss anemia(2) Increased destruction – hemolytic anemia(3) Impaired production of red blood cells – iron deficiency, megaloblastic, and aplastic anemias ○ characterized as normochromic (normal color) or hypochromic (decreased color). Red cells can also vary in size: normocytic (normal size), microcytic (small cells), and macrocytic (large cells). ○ Blood loss anemia may be internal or external, as well as either chronic or acute. Acute blood loss and decreased intravascular volume can lead to cardiovascular collapse and shock. Chronic blood loss does not affect blood volume but rather leads to depleted iron stores and iron deficiency anemia. In fact, up to 50% of red blood cells may be lost before any signs or symptoms occur. GI bleeding and menstrual disorders are a common cause of chronic blood loss anemia. The new red cells that are produced have less hemoglobin, which results in microcytic hypochromic anemia. ○ Hemolytic anemias have the following characteristics:Premature destruction of red cells, Retention of iron and other products of hemoglobin, and Increased erythropoiesis. red blood cell has a shortened life span, so the bone marrow is hyperactive, increasing the number of reticulocytes.also be inherited and can
vary in the degree of its severity. Two types of inherited hemolytic anemias are sickle cell disease and thalassemias. ■ Sickle cell disease characterized by chronic hemolytic anemia, pain, and organ failure caused by abnormal hemoglobin S (HbS). result of a single mutation in the hemoglobin molecule. Under conditions of decreased oxygen levels, the cell becomes sickled as the abnormal hemoglobin (HbS) begins to aggregate (stick
hypochromic, microcytic anemia due to decreased synthesis of the affected chain coupled with continued production and accumulation of the unaffected globin chain.impairs bone growth and leads to osteoporosis or osteopeniaIron overload from repeated transfusions is a major complication of treatment. The extra iron can be deposited in the myocardium, liver, and endocrine organs and are common causes of morbidity and mortality.Regular blood transfusions are necessary to keep hemoglobin levels at 9 to 10 g/dL. Iron chelation therapy is a way to reduce the iron overload and increase life expectancy. ○ Iron deficiency anemia (IDA) is common worldwide and is usually a result of dietary deficiencies, a loss of iron through bleeding, or increased demands. Iron is a component of heme, and a decrease in levels leads to impaired oxygen delivery.Chronic blood loss is the most common reason for IDA in the developed world. Menstrual bleeding, gastrointestinal bleeding, vascular lesions, intestinal polyps, hemorrhoids, or cancer are all potential causes of IDA.manifestations of IDA are related to decreased hemoglobin and impaired oxygen transport. Fatigue, palpitations, dyspnea, angina, and tachycardia may occur. Brittle hair and nails, spoon-shaped deformity of the fingernails, sores in the corners of the mouth can also occur. Some patients may
even have pica, the compulsive eating of ice, dirt, or other abnormal (non-food) substances.IDA presents with a low hemoglobin and hematocrit, decreased iron stores, low serum iron and ferritin levels, and increased total iron-binding capacity (TIBC). Low ferritin is the most specific (but not sensitive) test to diagnose IDA.For infants younger than 1 year of age, avoiding cow’s milk, and the use of iron-fortified formulas and cereals are recommended. After the first year, a diet
anemia caused by atrophic gastritis and failure to produce intrinsic factor leading to a decreased absorption of vitamin B 12. It is possibly caused by an autoimmune destruction of the gastric mucosa. Other causes include gastrectomy, ileal resection, inflammation or neoplasms, and malabsorption syndromes. The characteristics of the cells include flimsy membranes, oval rather than biconcave shape, and a shorter life span. ■ Folic Acid Deficiency produces an anemia with increased MCV and normal MCHC. Symptoms are similar, but without the neurologic changes.Folic acid is found in vegetables, fruits, cereals, and meats. It is rapidly absorbed from the intestine; however, much of the vitamin is lost in cooking. The most common causes of folic acid deficiency are malnutrition or lack of dietary intake, especially in older adults or alcoholics. The body requires 50 μg daily, and the body can store 2000- μg. Certain medications, and tumor cells, can block absorption. ○ Aplastic anemia occurs when the bone marrow fails to produce blood cells. ○ Anemia of chronic inflammation describes exactly what it is – an anemia that occurs due to chronic inflammation from a disease.
It can be caused by chronic infections like AIDS, cancers, or autoimmune disorders, like RA, SLE, or chronic kidney disease. Laboratory tests show a normocytic and normochromic mild anemia with high serum ferritin, low reticulocytes, low TIBC, and low transferrin saturation. Treatment focuses
