PATHOGENESIS & PATHOPHYSIOLOGY

Predisposing Factors: Precipitating Factors:

 Age  Environmental
UNKNOWN
 Gender ETIOLOGY  Drug-Induced
 Hereditary  Infection
 Race
 Hormonal

Female producing estrogen First generation familial possession of Infectious agent’s n the body
influencing SLE DNA

Manifestation of heightened levels Similar activity and/or structure to

of estrogen during puberty and Genetic relational DNA passes down to our own systemic cells.
pregnancy next generation

Unknown cause of estrogen

influencing immune response of the Human Leukocyte Antigen Class 1 and 2
HLA system in chromosome 6 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 Defect in mechanism of immune

complex clearance.
Secondary Necrosis of the cells Release of danger signals
Apoptotic chromatin
and nuclei attach to
Release of nuclear fragments as potential Endocytose of antigen material dendrite surface.
autoantigens. by dendritic cells

Defective B-cell
Impaired membrane integrity of dendritic Presented to T-cells activation by
cells autoantigens

Induced maturation of dendritic cells Activation of defective T-cells

Hyper reactivity of
defective B-cells
Production of defective helper T-
cells
Production of self and
non-self antibodies and
B memory cells

Various
Autoantibody Autoreactive cytotoxic T-cell activation Negative abnormal B-
cell contribution to
productions
already deficient
immune system.
Inflammation of the affected system
Production of Anti-Nuclear Systemic Lupus Erythematosus
Antibodies (ANA) in renal
cells
Antibodies bind with antigen
Production of ANA, anti-phospholipids, and other specific
autoantibodies.
Formation of immune
complexes
Anti- Lymphocytoto Antiphosphol
Leukocyte Infiltration erythrocyte xic antibody ipid antibody
antibody activation activation
Proteinuria activation
Compliment protein cascade

Recruitment of inflammatory Formation of defective immune complex

cells

Alteration in the permeability Hemolytic Hemolysis Direct WBC lysis

and structure of the Anemia
glomerular basement
Reduced RBC Reduced WBC
count count
Induced Glomerular Injury

Management and If not treated: Management and Lymphopenia

treatment: -Lupus Nephritis treatment:
-Immunosuppressant -Acute or chronic -Iron and Vitamin C
agents renal impairment supplements If not treated:
-Mycophenolate -End-stage renal -Blood Transfusions -Hypoxemia
Mofetil and failure -Immunosuppressant -Chronic Pulmonary
intravenous agents Disease
Cyclophosphamide
 Thrombocytopenia Platelet destruction
and reduction Cellular
membrane
component
damage
Platelet aggregation
and clot formation

Anti-phospholipids bind with

vascular cells.
Loss of blood Vascular wall
supply to the bone inflammation
Formation of immune
complex
Bone Necrosis Mononuclear cell
infiltration
Vascular Inflammation
Myalgias Involved Joint
Arthritis collapse
Occurrence of
immunoglobulin and
compliment disposition

Management and If not treated:

treatment: -Further Occurrence of tissue damage
Malar Rash
-Analgesics deterioration of Photosensitivity in the acute, subacute and
-Nonsteroidal anti- bones and joints. Discoid Rash chronic levels
inflammatory drugs
-lifestyle changes
(including exercise and
weight control)
 Management and treatment: If not treated:
-Nonsteroidal anti- -Further obstruction of
inflammatory drugs and tissue.
antimalarials -Necrosis of the tissue.
-Prevent exposure to light or -Gangrene may occur.
other environmental factors.

Anti-phospholipids and Anti-phospholipids and Specific autoantibody Production of direct

other specific other specific activation in the neuronal tissue
autoantibody activation autoantibody activation neuronal tissue antibodies
in the cardiac linings in the pleural linings

Formation of defective immune complex. Immune Activation of Altered cerebral

disposition cerebral functioning
activation vasculature
Noninfective Noninfective
inflammation of inflammation of the Psychosis
pericardium, membrane around the Micro and Macro vascular Lupus
Headache
myocardium and lungs thrombosis Seizures
endocardium

Cerebral edema and ischemia

Serositis
Elevated intracranial pressure
 Management and
treatment:
-Immunosuppressive
drugs
-Non-steroidal anti-
inflammatory drugs.
If not treated: Management and If not treated:
-Further inflammation treatment: -Progressive
-Infection and -Immunosuppressive intracranial
deterioration of drugs pressure.
myocardial and -Non-steroidal anti- -Deterioration of
pleural linings. inflammatory drugs. cerebral functions
-Lung Collapse -Multiple system
-Cardiac tamponade failure.
-Chronic constrictive
pericarditis.
-Congestive Heart
Failure.

Production of specific ANA in gastric cells Inflammatory response around the liver cells

Antibodies bind with self-antigen. Ineffective biliary cycle

Formation of immune complexes. Increased bilirubin in the body Jaundice

Upper and Lower gastrointestinal

inflammation

Gastric irritability in Peritoneal Abdominal

the stomach spasms Pain
Increased gastric acid Ineffective defecation
content

Induced reflux of Nausea and Management and If not treated:

gastric acid treatment: -Severe Diarrhea
Vomiting
-Immunosuppressive
drugs
-Laxatives to
promote effective
Management and If not treated: bowel movement
treatment: Stomach ulceration
-Immunosuppressive
drugs
-Antiemetic:
metacropamide
 Patofisiologi SLE belum didefinisikan sepenuhnya, meskipun banyak gen yang
mempengaruhi fungsi kekebalan tubuh, terutama human leukocyte antigen (HLA), dapat
meningkatkan kerentanan terhadap penyakit klinis. Kebanyakan kembar monozigot (identik)
tidak sama di SLE klinis, perlu diinvestigasi bahwa faktor-faktor tambahan, mungkin
lingkungan, memicu perkembangan luas autoimunitas pada individu yang rentan.

Obat-obatan tertentu (misalnya, fenitoin) dapat menghasilkan lupus yang diinduksi oleh
obat, tetapi kelainan ini berbeda dari SLE klasik dalam autoantibodinya (misalnya, antibodi
antihiston positif) dan pada sebagian wilayah ginjal serta central nervous system (CNS). Setelah
dipicu, reaksi autoimun SLE mempengaruhi banyak situs melalui berbagai mekanisme seperti
pengendapan kompleks imun, efek sitokin dan neuromodulator kimia lainnya, serangan langsung
oleh autoantibodi atau leukosit yang diaktifkan, dan lain-lain.

Bagian yang tidak termasuk system saraf yang mengalami kerusakan antara lain
glomeruli ginjal, sendi, serosa pleura atau perikardial, integumen, endotelium jantung atau
pembuluh darah, katup jantung, dan mukosa oral dan konjungtiva. Beberapa tempat yang telah
disebutkan mungkin terlibat dalam sistem saraf.

Satu mekanisme yang diusulkan untuk pembuatan dan perkembangan autoantibodi

melibatkan kelainan pada apoptosis yang menyebabkan peningkatan kematian sel dan gangguan
toleransi imun. Redistribusi antigen seluler selama apoptosis mengarah ke tampilan permukaan
sel plasma dan antigen inti dalam bentuk nukleosom. Dengan demikian, limfosit yang tidak
diregulasi (tidak toleran) mulai menargetkan antigen intraseluler yang dilindungi secara normal.

Kompleks imun terbentuk dalam mikrovaskatur, yang mengarah pada aktivasi

komplemen dan peradangan. Selain itu, kompleks antibodi-antigen menempel pada membran
basal kulit dan ginjal. Pada SLE aktif, proses ini telah dikonfirmasi berdasarkan keberadaan
kompleks antigen inti seperti DNA, imunoglobulin, dan protein pelengkap di situs ini. Serum
antinuclear antibodies (ANAs) ditemukan pada hampir semua individu dengan SLE aktif, dan
antibodi terhadap native double-stranded DNA (dsDNA) relatif spesifik untuk diagnosis SLE.