Gilead -Topics in
Human Pathophysiology
Fall 2010
Drug Safety and Public Health
Phagocytosis
Inflammation
Complement
Interferon
Figure 21.5

B lymphocytes
◦ Mature in bone marrow, responsible for antibody
mediated immunity
◦ When they recognize a pathogen (antigen) and are
activated, develop into plasma cells and memory
cells
◦ Plasma cells produce 1000s of antibodies
(immunoglobulins) per second
B lymphocytes –
•Recognition
•Activation
•Attack (cloning
and antibody
production)
Antibody functions
Figure 21.14

T lymphocytes
◦ 3 types: helper T cells, cytotoxic T cells, suppressor
T cells
◦ When recognize a pathogen and are activated, these
attack the pathogen and create a cadre of memory
cells




Recognize pathogen presented by other WBCs
Are activated by cytokines by other WBCs
“Clone”themselves to form active cells and
memory cells
Release cytokines to activate and stimulate
other WBCs, including B cells and phagocytes
Macrophages
act as antigen
presenting
cells
•Helper T cells
are presented
with antigen by
specialized
WBCs
•When
activated these
helper T cells
clone
themselves
into memory
Figure 21.17





AKA killer T cells
Recognize pathogen (antigens) in virally
infected cell or cancer cells
Activated by cytokines from helper T cells
“Clone” themselves into attack cells and
memory cells
Attack by producing proteins that open holes
in infected cells
Figure 21.19


Memory cells circulate, sometimes for a
lifetime, scanning for that pathogen they
recognize
A second infection by the same pathogen will
yield a stronger, faster immune response that
prevents illness
Figure 21.12




A retrovirus that infects host cells
macrophages and helper T cells
Its RNA is reverse transcribed into DNA, then
inserted into host chromosomes
Protein synthesis of viral DNA makes
components of new HIV
The components are assembled into new
virus and released from host
Reverse
transcriptase
required
Protease
required
Reverse
transcriptase
Inhibitors work
here
Protease
inhibitor
s work
here
Gilead -Topics in
Human Pathophysiology
Fall 2010
Drug Safety and Public Health
Digestive system
The Liver
Part 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
Liver Functions
Secretes bile
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
Figure 26.19b
Hepatitis
•Inflammation of the liver
•Causes include:
• Viruses
• Drug toxicity
• Wild mushroom
poisoning
Viral Hepatitis
Hepatitis A (HAV)
Hepatitis B (HBV)
Hepatitis C (HCV)
Etiology
Causes mild acute Causes acute illness and
illnesschronic liver disease, can
hepatocyte injury 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-oral
primarily 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 vaccine
From http://www.cdc.gov/hepatitis/index.htm
Figure 9.20
Reverse transcriptase
required
Pathophysiology of Hepatitis
• Destruction of hepatocytes by inflammation
with edema and altered blood flow
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 kidneys
See labtestsonline for more information
Additional Liver Tests
• Diagnostic tests for viral hepatitis – either
serum tests for viral antigens, or serum tests
for antibodies to the virus(indicating
exposure)
• Imaging – CT scan, ultrasound, MRI
• Biopsy
CT Scan of the Liver
Normal liver
Nodular cirrhotic liver with ascites
www.integris-health.com
40
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
Viral Hepatitis Treatment
• Symptomatic support – diuretics,
meds to decrease N load, Vit. K
• Antivirals:
• Interferons
• Ribavirin
• Surgery