Hepatic Pathology and Respiratory SystemTopics in Human Pathophysiology Fall 2011Gilead Drug Safety and Public Health

Outline Hepatic Pathophysiology

Digestive System Overview Placement and role of liver Liver microstructure Pathologies of liver

Respiratory Structure and Function

Digestive system

The LiverPart of digestive system

Located in upper right abdominal quadrant

Is served by two blood vessels: the hepatic portal vein, the hepatic artery

Has one duct that carries bile away from it to the gall bladder for storage

Composed of lobules that contain hepatocytes

Blood moves easily from the external vessels, in porous capillaries past the hepatocytes to a central vein

Hepatocytes do the work of the liver

Figure 14.11

Hepatic Portal System

Liver Functions

Secretes bile – which emulsifies fats within small intestine

Metabolizes bilirubin - a breakdown product of hemoglobin

Produces albumin, and clotting factors

Metabolizes fats, proteins, carbohydrates, stores glycogen, makes HDLs and LDLs

Inactivates many biologically active chemicals including alcohol, medicinal and recreational drugs, hormones, poisons

Stores fat soluble vitamins and iron

Converts ammonia (NH3) into soluble urea to be excreted by kidneys

Hepatitis• Inflammation of the liver• Causes include:

• Viruses and other pathogens

• Drug and alcohol toxicity

• Environmental toxins• Obesity, autoimmune

disorders

Viral HepatitisHepatitis A (HAV)

Hepatitis B (HBV) Hepatitis C (HCV)

Etiology Causes mild acute illness- hepatocyte injury

Causes acute illness and chronic liver disease, can lead to liver cancer

May cause acute illness, acts long term leading to chronic liver disease and risk of liver cancer

Mode of transmission

Fecal-oralprimarily in children, young adults

Contact with infected body fluids – blood, semen; contaminated needles, mother to newborn

Contact with infected blood, mostly through contaminated needles

Vaccination Hep A vaccine Hep B vaccine No vaccineFrom http://www.cdc.gov/hepatitis/index.htm

Figure 9.20

Reverse transcriptase required

Pathophysiology of Hepatitis Destruction of hepatocytes (necrosis) by

inflammation Altered blood flow through and to liver Edema – both peripherally and in portal vessel area Blockage of bile ducts leading to reduced bile in

small intestine and problems with fat absorption Reduction of ability to make blood proteins including

albumin, clotting factors, complement Buildup of blood toxins including urea and ammonia

Symptoms of Hepatic Damage Jaundice Dark amber colored urine Nausea/vomiting Abdominal pain - R upper

quad Fatigue Also- ascites, hepatic

encephalopathy, coma, death

Cirrhosis Long term

result of liver damage

Liver Tests – Liver Panel AST– liver enzyme, elevated with damage to cells ALT - liver enzyme, elevated with damage to cells ALP – enzyme related to bile ducts, levels elevate

if there is a blockage total bilirubin (blood)– may be elevated with liver

damage or excessive RBC destruction Albumin (blood) – checks on synthetic ability of

liver cells prothrombin time - decreased synthesis of

clotting factors by liverSee labtestsonline for more information

CT Scan of the Liver

17

Nodular cirrhotic liver with ascitesNormal liver

www.integris-health.com

Drug Induced Hepatotoxicity More than 900 drugs, toxins

and herbs cause drug induced hepatotoxicity,

20-40% of all fulminant liver failure cases are caused by drug induced hepatotoxicity

It is the most common reason a drug is withdrawn from approval

Damage to liver can be hepatocellular or cholestatic

Drug-Induced Hepatotoxicity from http://www.emedicine.com/Med/topic3718.htm

Figure 10.1 Respiratory System

Gas exchange Protection Speech Compression of abdomen and spine

stiffening Acid-Base balance

Respiratory Functions

Figure 10.8

Respiratory Interface

Alveolar wall

Capillary wall

Surfactant

Gas Exchange occurs by diffusion