PATHOPHYSIOLOGY Predisposing Factors: θ Age θ Gender θ Hereditary θ Race θ Hormonal Female producing estrogen Manifestation of heightened levels of estrogen during puberty and pregnancy Unknown cause of estrogen influencing immune response of the HLA system in chromosome 6
Precipitating Factors: θ Environmental θ Drug-Induced θ Infection
UNKNOWN ETIOLOGY
First generation familial possession of influencing SLE DNA Genetic relational DNA passes down to next generation
Infectious agent’s n the body Similar activity and/or structure to our own systemic cells.
Human Leukocyte Antigen Class 1 and 2 in chromosome 6 possess multiple genes influenced in inheriting SLE. Spontaneous occurrence of SLE activation.
Human Leukocyte Antigen Class 1 and 2 in chromosome 6 possess multiple genes influenced in inheriting SLE.
Fewer or defective Tingible Body Macrophages in the body Defective clearance of early apoptotic cells Secondary Necrosis of the cells
Defect in mechanism of immune complex clearance. Release of danger signals
Release of nuclear fragments as potential autoantigens.
Endocytose of antigen material by dendritic cells
Impaired membrane integrity of dendritic cells
Presented to T-cells
Induced maturation of dendritic cells
Activation of defective T-cells Production of defective helper Tcells
Apoptotic chromatin and nuclei attach to dendrite surface. Defective B-cell activation by autoantigens
Hyper reactivity of defective B-cells Production of self and non-self antibodies and B memory cells
Various Autoantibody productions
Autoreactive cytotoxic T-cell activation
Inflammation of the affected system
Negative abnormal Bcell contribution to already deficient immune system.
Production of Anti-Nuclear Antibodies (ANA) in renal
Systemic Lupus Erythematosus
Antibodies bind with antigen
Production of ANA, anti-phospholipids, and other specific autoantibodies.
Formation of immune complexes Leukocyte Infiltration Compliment protein cascade
Proteinuria
Recruitment of inflammatory cells Alteration in the permeability and structure of the glomerular basement
Lymphocytoto xic antibody activation
Antiphospholi pid antibody activation
Formation of defective immune complex Hemolyti c Anemia
Induced Glomerular Injury Management and treatment: -Immunosuppressant agents -Mycophenolate Mofetil and intravenous Cyclophosphamide
Antierythrocyte antibody activation
If not treated: -Lupus Nephritis -Acute or chronic renal impairment -End-stage renal failure
Hemolysis Reduced RBC count
Management and treatment: -Iron and Vitamin C supplements -Blood Transfusions -Immunosuppressant agents
Direct WBC lysis Reduced WBC count
Lymphopeni a If not treated: -Hypoxemia -Chronic Pulmonary Disease
Thrombocytopenia
Platelet destruction and reduction
Platelet aggregation and clot formation
Cellular membrane component damage
Anti-phospholipids bind with vascular cells. Loss of blood supply to the bone
Bone Necrosis
Myalgias Arthritis
Management and treatment: -Analgesics -Nonsteroidal antiinflammatory drugs -lifestyle changes (including exercise and weight control)
Vascular wall inflammation
Mononuclear cell infiltration
Involved Joint collapse
If not treated: -Further deterioration of bones and joints.
Formation of immune complex Vascular Inflammation Occurrence of immunoglobulin and compliment disposition
Malar Rash Photosensitivit y Discoid Rash
Occurrence of tissue damage in the acute, subacute and chronic levels
Management and treatment: -Nonsteroidal anti-inflammatory drugs and antimalarials -Prevent exposure to light or other environmental factors.
Anti-phospholipids and other specific autoantibody activation in the cardiac linings
Anti-phospholipids and other specific autoantibody activation in the pleural linings
Formation of defective immune complex.
Noninfective inflammation of pericardium, myocardium and endocardium
Noninfective inflammation of the membrane around the lungs
If not treated: -Further obstruction of tissue. -Necrosis of the tissue. -Gangrene may occur.
Specific autoantibody activation in the neuronal tissue
Immune disposition activation
Activation of cerebral vasculature
Micro and Macro vascular thrombosis
Cerebral edema and ischemia Serositis Elevated intracranial pressure
Production of direct neuronal tissue antibodies
Altered cerebral functioning
Psychosis Lupus Headache Seizures
Management and treatment: -Immunosuppressive drugs -Non-steroidal antiinflammatory drugs.
If not treated: -Further inflammation -Infection and deterioration of myocardial and pleural linings. -Lung Collapse -Cardiac tamponade -Chronic constrictive pericarditis. -Congestive Heart Failure.
Production of specific ANA in gastric cells Antibodies bind with self-antigen. Formation of immune complexes.
Management and treatment: -Immunosuppressive drugs -Non-steroidal antiinflammatory drugs.
Inflammatory response around the liver cells Ineffective biliary cycle Increased bilirubin in the body
Upper and Lower gastrointestinal inflammation
Gastric irritability in the stomach
Peritoneal spasms
Abdominal Pain
Jaundic e
If not treated: -Progressive intracranial pressure. -Deterioration of cerebral functions -Multiple system failure.
Increased gastric acid content
Induced reflux of gastric acid
Management and treatment: -Immunosuppressive drugs -Antiemetic: metacropamide
Ineffective defecation
Nausea and Vomiting
If not treated: Stomach ulceration
Management and treatment: -Immunosuppressive drugs -Laxatives to promote effective bowel movement
If not treated: -Severe Diarrhea
NARRATIVE PATHOPHYSIOLOGY The pathophysiology of SLE has not been defined fully, although many genes that affect immune function, particularly the human leukocyte antigen (HLA), may augment susceptibility to clinical disease. Most monozygotic (identical) twins are discordant for clinical SLE, strongly suggesting that additional factors, probably environmental, trigger the widespread development of autoimmunity in susceptible individuals. Certain medications (eg, phenytoin, hydralazine, procainamide, and isoniazid) may produce drug-induced lupus, but this disorder differs from classic SLE in its autoantibody profile (eg, antihistone antibody positive) and in sparing the kidneys and central nervous system (CNS). Once triggered, SLE's autoimmune reaction affects many sites through multiple mechanisms such as deposition of immune complexes, effects of cytokines and other chemical neuromodulators, direct attack by autoantibodies or activated leukocytes, and others. Non-neurologic sites of damage include the renal glomeruli, joints, pleural or pericardial serosa, integument, cardiac or vascular endothelium, cardiac valves, and the oral and conjunctival mucosa. Multiple sites may be involved within the nervous system. One proposed mechanism for the development of autoantibodies involves a defect in apoptosis that causes increased cell death and a disturbance in immune tolerance. The redistribution of cellular antigens during apoptosis leads to a cell-surface display of plasma and nuclear antigens in the form of nucleosomes. Thus, dysregulated (intolerant) lymphocytes begin targeting normally protected intracellular antigens. Immune complexes form in the microvasculature, leading to complement activation and inflammation. Moreover, antibody-antigen complexes deposit on the basement membranes of skin and kidneys. In active SLE, this process has been confirmed based on the presence of complexes of nuclear antigens such as DNA, immunoglobulins, and complement proteins at these sites. Serum antinuclear antibodies (ANAs) are found in virtually all individuals with active SLE, and antibodies to native double-stranded DNA (dsDNA) are relatively specific for the diagnosis of SLE.
