Systemic Lupus Erythematosus Pathophysiology
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Transcript of Systemic Lupus Erythematosus Pathophysiology
PATHOPHYSIOLOGY
UNKNOWNETIOLOGY
Predisposing Factors: Age Gender Hereditary Race Hormonal
Precipitating Factors: Environmental Drug-Induced Infection
Female producing estrogen
Manifestation of heightened levels of estrogen during puberty and
pregnancy
First generation familial possession of influencing SLE DNA
Genetic relational DNA passes down to next generation
Human Leukocyte Antigen Class 1 and 2 in chromosome 6 possess multiple genes
influenced in inheriting SLE.
Infectious agent’s n the body
Similar activity and/or structure to our own systemic cells.
Unknown cause of estrogen influencing immune response of the
HLA system in chromosome 6
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
Release of nuclear fragments as potential autoantigens.
Impaired membrane integrity of dendritic cells
Induced maturation of dendritic cells
Release of danger signals
Endocytose of antigen material by dendritic cells
Presented to T-cells
Activation of defective T-cells
Production of defective helper T-cells
Defect in mechanism of immune complex clearance.
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
Negative abnormal B-cell contribution to already deficient immune system.
Autoreactive cytotoxic T-cell activationVarious
Autoantibody productions
Inflammation of the affected system
Systemic Lupus Erythematosus
Production of ANA, anti-phospholipids, and other specific autoantibodies.
Production of Anti-Nuclear Antibodies (ANA) in renal
Antibodies bind with antigen
Formation of immune complexes
Leukocyte Infiltration
Compliment protein cascade
Recruitment of inflammatory cells
Alteration in the permeability and structure of the glomerular basement
Induced Glomerular Injury
Management and treatment:-Immunosuppressant agents-Mycophenolate Mofetil and intravenous Cyclophosphamide
If not treated:-Lupus Nephritis-Acute or chronic renal impairment-End-stage renal failure
Proteinuria
Anti-erythrocyte antibody activation
Lymphocytotoxic antibody activation
Antiphospholipid antibody activation
Formation of defective immune complex
Hemolysis
Reduced RBC count
Direct WBC lysis
Reduced WBC count
Hemolytic Anemia
Lymphopenia
If not treated:-Hypoxemia-Chronic Pulmonary Disease
Management and treatment:-Iron and Vitamin C supplements-Blood Transfusions-Immunosuppressant agents
Anti-phospholipids bind with vascular cells.
Cellular membrane component damage
Platelet destruction and reduction
Platelet aggregation and clot formation
Thrombocytopenia
Formation of immune complex
Vascular Inflammation
Occurrence of immunoglobulin and
compliment disposition
Vascular wall inflammation
Mononuclear cell infiltration
Loss of blood supply to the bone
Bone Necrosis
Involved Joint collapse
MyalgiasArthritis
Occurrence of tissue damage in the acute, subacute and
chronic levels
Malar RashPhotosensitivit
yDiscoid Rash
Management and treatment:-Analgesics-Nonsteroidal anti-inflammatory drugs-lifestyle changes (including exercise and weight control)
If not treated:-Further deterioration of bones and joints.
Management and treatment:-Nonsteroidal anti-inflammatory drugs and antimalarials-Prevent exposure to light or other environmental factors.
If not treated:-Further obstruction of tissue.-Necrosis of the tissue.-Gangrene may occur.
Production of direct neuronal tissue
antibodies
Anti-phospholipids and other specific autoantibody activation in the cardiac linings
Anti-phospholipids and other specific autoantibody activation in the pleural linings
Specific autoantibody activation in the neuronal tissue
Formation of defective immune complex. Immune disposition activation
Activation of cerebral vasculature
Noninfective inflammation of pericardium, myocardium and endocardium
Noninfective inflammation of the membrane around the lungs
Micro and Macro vascular thrombosis
Cerebral edema and ischemia
Elevated intracranial pressure
Altered cerebral functioning
Serositis
PsychosisLupus
HeadacheSeizures
If not treated:-Further inflammation-Infection and deterioration of myocardial and pleural linings.-Lung Collapse-Cardiac tamponade-Chronic constrictive pericarditis.-Congestive Heart Failure.
Management and treatment:-Immunosuppressive drugs-Non-steroidal anti-inflammatory drugs.
Management and treatment:-Immunosuppressive drugs-Non-steroidal anti-inflammatory drugs.
If not treated:-Progressive intracranial pressure.-Deterioration of cerebral functions-Multiple system failure.
Production of specific ANA in gastric cells
Antibodies bind with self-antigen.
Formation of immune complexes.
Upper and Lower gastrointestinal inflammation
Inflammatory response around the liver cells
Ineffective biliary cycle
Increased bilirubin in the body Jaundice
Gastric irritability in the stomach
Peritoneal spasms
Abdominal Pain
Increased gastric acid content
Ineffective defecation
Induced reflux of gastric acid
Nausea and Vomiting
Management and treatment:-Immunosuppressive drugs-Antiemetic: metacropamide
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.