Pathophysiology_perihilar Cholangiocarcinoma

Predisposing Factors: • Age • Gender • Race

• • •

Etiology: UNKNOWN

Precipitating Factors: Toxins Exposure Parasitic Infection Chronic Inflammation in the Bile Ducts

Mutations in the oncogenes k-ras, c-myc, c-neu, eerb-b2, and c-met, and in the tumor suppressor genes p53 and bcl-2

Affects the transcription of the Fas-gene

Proliferation of genetically unstable cells in the bile duct

Malignant transformation of unstable cells in the bile duct

Obstruction in the bile duct

• • • • •

If unmanaged

•

Management: Surgery

•

Diagnostic Tests: Abdominal USD CT scan ERCP PTC PET MR – cholangiography Tumor markers

A

41

A

• •

Mgt.: Chemotheraphy Radiation therapy Mgt.: PTBD

Continuous proliferation of unstable cells and obstruction in the flow of bile

Diminish host antibacterial defenses in the bile duct • • •

Bile builds up in the liver and seeps out into the bloodstream

• • If unmanaged

Damage to the liver cells

Scarring of the liver

S/Sx: Jaundice Pruritus Clay-colored stools Dark urine Abdominal pain

Diagnostic Tests: • Liver enzymes (ALT & AST) • Prothrombin time

Mgt.: antibiotics

Bacterial colonization in the bile duct and small bowel

•

Sx: fever

If unmanaged

Sepsis

DEATH

Liver failure

Disorders of synthesis and storage functions

B

Disorders of metabolic and excretory functions

C 42

B

Hepatocytes unable to synthesize clotting factors

Hepatic cells unable to take up and store glucose • Hypoglycemic events

If unmanaged

Unconsciousness

Permanent brain damage

• • • •

S/Sx: Visual disturbance s Heart palpitations Tremors Anxiety Sweating

Hepatocytes unable to synthesize transporter proteins

Bleeding

• •

If unmanaged

Hypovolemic shock

Management: • Glucose tablets or candy • IV infusion of dextrose

•

•

Signs: Bruising Spontaneous bleeding Blood in the urine or stool

Management: Infusion with clotting factors

B4

Hypoalbuminemia

Fluid shifting

If unmanaged

•

Sign: edema

Management: • Albumin transfusion

Skin breakdown (ulceration)

Management: • Antibiotics

Localized Infection

Sx: • fever

If unmanaged

Overwhelming infection/sepsis

DEATH

43

B4

C

Hepatocytes unable to synthesize bile components such as bile salts

J Impaired fat absorption

•

Deficiency of fat-soluble vitamins

•

Malnutrition

• •

•

Sx: Fatty stool S/Sx: Dry, scaly skin Bruising Hair loss

Liver unable to convert Kto urea ammonia

Hepatic encephalopathy

Coma

C2

• • •

C3 S/Sx: Asterixis Fetor hepaticus Lack of mental alertness

Cold intolerance

Lower resistance to infection

Infection Sepsis

DEATH

44

C2

C3

Liver unable to modify the hormones

Increased aldosterone

Liver unable to metabolize the drugs

•

Increased androgen/estrogen

• Sodium and water retention If unmanaged

•

Sign: edema

S/Sx: Gynecomas tia Testicular atrophy

Drug toxicity

Management: • Diuretics

Skin breakdown (ulceration)

Localized Infection If unmanaged

•

Sx: fever

Management: • Antibiotics

Overwhelming infection/sepsis

DEATH

45

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