Pathoma - Section 4 - Fundamentals Of Pathology

Front 1

Free radicals are chemical species with an _____________ in their __________.

Back 1

unpaired electron; outer orbit

Front 2

Physiologic generation of ___________ occur during oxidative phosphorylation. How does it occur?

Back 2

free radicals

Partial reduction of yields superoxide (O2*-, hydrogen peroxide (H202), and hydroxyl radicals (*OH).

Front 3

Complex IV in the ETC is the enzyme ___________.

Back 3

cytochrome c oxidase

Front 4

Cytochrome c transfers _________ to ___________.

Back 4

electrons; oxygen

Front 5

Oxygen accepts ___ electrons before becoming water.

Back 5

4

Front 6

What ROS are made when oxygen is partially reduced by 1, 2, 3 and 4 electrons respectively?

Back 6

O2 --> O2*- --> H2O2 --> OH* --> H2O

Front 7

Free radicals can be generated pathologically. How? What ROSes are produced in each case?

Back 7

(1) Ionizing radiation (e.g. X-ray and gamma radiation). Hydroxyl ion (radiation hits water within tissues and knocks off an electron)
(2) Inflammation (respiratory burst)
(3) By interaction with metals (e.g., copper and iron) via the fenton reaction.
(4) Drugs and chemicals (e.g., acetaminophen is metabolized in liver causing free radicals in the process, causes massive liver necrosis, a chemical is CCl4)

Front 8

This free radical is the most damaging one. What vitamin is the best neutralizer of this free radical?

Back 8

Hydroxyl ion.

Vitamin C

Front 9

In the first step of oxidative burst in neutrophils, the enzyme ___________ converts oxygen to _________.

Back 9

NADPH oxidase; superoxide

Front 10

The second step of oxidative burst in neutrophils is mediated by _______________, producing ___________.

Back 10

superoxide dismutase; hydrogen peroxide

Front 11

____________ is a copper-transport plasma protein.

Back 11

Ceruloplasmin

Front 12

Ceruloplasmin contains ____ atoms of copper in its structure.

Back 12

6

Front 13

Ceruloplasmin represents ____ to ____ & of the total serum copper concentration.

Back 13

90%; 95%

Front 14

The inheritance pattern of Wilson's disease is ________.

Back 14

AR

Front 15

What is Wilson's disease?

Back 15

An autosomal recessive disease associated with a defect in secreting copper into bile and in incorporating copper into ceruloplasmin.

Front 16

Provide three examples of enzymes that require copper to function.

Back 16

(1) SOD
(2) Cytochrome c oxidase
(3) Tyrosinase

Front 17

__________, a soluble iron-protein complex, is the storage form of iron in the ____________, ______, _______, and ________.

Back 17

ferritin; intestinal mucosa; liver; spleen; marrow

Front 18

Ferritin is synthesized (in/by) ________.

Back 18

macrophages

Front 19

Serum ferritin levels reflect ____________ in the bone marrow.

Back 19

iron stores

Front 20

What is the best screening test for iron deficiency and iron overload disorders?

Back 20

Serum ferritin is the best screening test for iron deficiency and iron overload disorders (e.g., hemochromatosis).

Front 21

Hemosiderin is a ___________ degradation product.

Back 21

ferritin

Front 22

Patients who require ongoing transfusions are at risk for ____________.

Back 22

hemosiderosis

Front 23

___________ is the primary binding protein for iron (transport).

Back 23

Transferrin

Front 24

When iron stores in the bone marrow macrophages are decreased (e.g., iron deficiency), liver synthesis of transferrin __________ (increases/decreases), which increases ___________.

Back 24

increases; total iron-binding capacity (TIBC)

Front 25

What is the most common AR disorder?

Back 25

Hemochromatosis

Front 26

Alcohol __________ (increases/decreases) ________ absorption.

Back 26

increases; iron

Front 27

What's the real problem with free radicals? What do they do?

Back 27

(1) Peroxidation of lipids
(2) Oxidation of DNA and proteins
• ROS are implicated in oncogenesis.

Front 28

How do antioxidants prevent FR damage?

Back 28

They neutralize them by DONATING one of their own electrons, thereby preventing the "electron stealing" of FRs. Antioxidants remain stable and do not become and FR.

Front 29

Vitamin C neutralizes FRs produced by ___________ and ___________.

Back 29

pollutants; cigarette smoke

Front 30

Smokers have decreased levels of ____________ because they are used up in neutralizing FRs derived from cigarette smoke.

Back 30

vitamin C

Front 31

Vitamin E prevents ____________

Back 31

lipid peroxidation in cell membranes.

Front 32

Vitamin E neutralizes what lipoprotein?

Back 32

Oxidized LDL

Front 33

In what cell compartment do selenium neutralize FRs?

Back 33

cytosol

Front 34

Glutathione is located in the __________________ pathway.

Back 34

pentose phosphate

Front 35

Catalase, present within ________ degrades _________ into water and oxygen.

Back 35

peroxisomes; peroxide

Front 36

One treatment of acetaminophen FR injury?

Back 36

N-acetylcysteine. It increases synthesis of glutathione for neutralization of drug FRs.

Front 37

Acetaminophen may cause _______________.

Back 37

diffuse chemical hepatitis (liver cell necrosis initially occurring around the central veins (zone III)

Front 38

Acetaminophen induced liver cell necrosis can occur at nontoxic levels in _________.

Back 38

alcoholics

Front 39

In the cytosol, retinol is irreversibly _________ to ____________, in a similar fashion to __________ and __________.

Back 39

oxidized; retinoic acid; steroids; vitamin D

Front 40

What three major enzymes are important in elimination of FRs?

Back 40

(1) SOD
(2) Glutathione peroxidase
(3) Catalase

Fit them in here:
O2 --> O2*- --> H2O2 --> OH* --> H2O

Front 41

CCl4 might show up in a clinical vignette as a person in the ____________ industry.

Back 41

dry cleaning

Front 42

What happens when CCl4 gets into your body?

Back 42

It gets into the blood, gets converted into CCl3 (P-450 system of the liver). CCl3 is now a free radical. Reversible injury occurs, with cellular swelling. RER ribosomes detach, protein synthesis is reduced. This diminishes apolipoprotein synthesis. Fat can then enter the liver but not go out. Fatty change in the liver is seen.

Front 43

What is reperfusion injury?

Back 43

Restoration of blood flow has consequences:
(1) Hypoxic endothelium increases adhesion molecules, recruiting circulating neutrophils
(2) Superoxide FRs are generated
(3) Calcium influx irreversibly damages injured cells

Front 44

A patient has an MI. The cardiac enzymes are increasing. After the artery is relieved of stenosis, the cardiac enzymes continue to rise. What is happening?

Back 44

Reperfusion injury

Front 45

A baby is treated for RDS with 60% oxygen. What may happen?

Back 45

Retinopathy of prematurity. Blindness may occur in the treatment of RDS with an O2 concentration > 50%.