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.