Systemic Lupus Erythematosus Pathophysiology

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.