Fall 2011 - Gen Path - Test 1 - Cell Injury

Front 1

cell injury vs cell death

Back 1

injury = reversible

death = not

Front 2

what cellular systems are vulnerable to injury

Back 2

cell membrane

genetic apparatus

energy supply

proteins

Front 3

causes of cell membrane injury

Back 3

trauma

free radicals

weaponized pores

Front 4

sources of free radicals

Back 4

radiation injury

toxicity

inflammation
- oxidative burst
- nitric oxide

normal cell fxn

Front 5

what causes weaponized pores

Back 5

complement cascade

bacterial hemolysins

Front 6

what causes DNA injury

Back 6

free radicals

viruses

toxins

radiation

Front 7

what injures cells by affecting energy supply

Back 7

toxins
- ie aflatoxin inhibits FA oxidation

hypoxia

Front 8

what causes protein injury

Back 8

toxins

heat/life -> heat shock proteins

Front 9

heat shock proteins

Back 9

produced in response to heat or stress

act intracellularly
- recognize
- bind
- chaperone
- refold
- degrade (chaperone to lysosome)

conserved throughout evolution

some role in
- autoimmune dz
- chemotherapy
- anoxia survival

Front 10

response to injury depends on

Back 10

type of cell

nutrition

previous injury

Front 11

what are the 1st cells affected by injury?

what other tissues are intermediately sensitive? very resistant?

Back 11

extremely sensitive
- neurons

intermediate susceptibility
- myocardium
- hepatocytes
- renal tubular epithelium

slow to be injured/ die
- fibroblasts
- epidermis
- skeletal muscle

Front 12

Give an example where response to injury depends on nutrition

Back 12

white muscle dz

Vit E and Selenium deficiency
- both are antioxidants
- they are component of glutathion peroxidase

Front 13

true or false

That which does not kill us makes us stronger

Back 13

false...

just ask my poor neurons right now after looking at this stuff for so long...

Front 14

morphology of injury

Back 14

fatty change

protein accumulation

glycogen accumulation

hydropic degeneration

Front 15

____ is the most clinically significant morphology of cellular injury

Back 15

fatty change

Front 16

mechanisms of fat accumulation in hepatocytes

Back 16

excessive entry of fatty acids
- foie gras

defective oxidation of fatty acids
- anoxia
- many toxins (such as aflatoxin)

decreased apoprotein synthesis
- protein malnutrition
- less protein coming in makes fat not able to get out of cell

defective secretion of lipoproteins
- toxins such as alcohol

Front 17

hydropic degeneration

Back 17

reversible cell swelling that follows ischemia

transient change that is rarely seen (exc in epithelium)

cells enlarged with clear watery cytoplasm
- identical to glycogen accumulation

may reverse to normal fxn or progress to cell rupture & death

Front 18

what happens to free fatty acids in circulation normally

Back 18

free fatty acids

intracellular fatty acids
-> oxidation in mitochondria
or
-> lipid exports (cholesterol/ phospholipids/ triglycerides)
+ apoprotein
->lipoprotein
-> leaves cell -> circulating lipoproteins

Front 19

feline hepatic lipidosis syndrome pathogenesis

Back 19

fat cat stops eating

-> mobilization from large fat stores

-> EXCESSIVE FA ENTER LIVER

-> lipid processing is overwhelmed

-> protein availability reduced by anorexia

-> DECREASED LIPID EXPORT

-> fatty change

-> liver dysfxn

-> icterus and anorexia

-> fat yellow cat

-> still not eating

-> repeat cycle

-> dead fat yellow cat

Front 20

ruminant fatty change

Back 20

late preg or early lactation in over-conditioned animals

intake doesn't keep up with nutritional demand

large fat stores mobilized

-> fatty liver

Front 21

morphology of fatty change

Back 21

grossly
- enlarged
- tan-yellow
- may float if severe
- friable

histologically
- clear, round, discrete cytoplasmic vacuoles

feline renal tubular epithelium normally contains cytoplasmic lipid (don't confuse this with fatty change)

Front 22

fatty infiltration

Back 22

infiltration of adipose CELLS into non-adipose tissue

different from fatty change (intracellular accumulation of lipid in non-adipose cells)

most common in heart and pancreas

Front 23

define free radical

how does it cause damage

Back 23

chemical with unpaired electron in outer orbit

extremely unstable/ reactive

damages membrane lipids by lipid peroxidation

Front 24

what creates free radicals

Back 24

radiation injury
- sunlight-induced skin damage

toxicity
- many toxins converted into free radicals
- cigarette smoke
- oxygen
- carbon tetrachloride CCL4
- chemotherapeutic agents

inflammation
- killing by neutrophils and macrophages requires oxidatice burst
- nitric oxide from endothelial and inflammatory cells is a free radical

normal cell fxn produces free radicals from oxygen

Front 25

_____ is the most toxic free radical

Back 25

OH-

Front 26

what antioxidants are constantly needed to inactivate free radicals

Back 26

Vitamin E/ Selenium
- selenium is a component of glutathione peroxidase

albumin, ceruloplasmin, & transferrin
- bind copper and iron

Front 27

know the normal cell fxn and how it results in free radicals

Back 27

O2

=> oxidases in mitochondria, ER, peroxisomes, and cytoplasm

-> O2-

=> superoxide dismutase

-> H2O2

=> ferrous iron & other transitional metals

-> OH-

=> glutathione peroxidase

-> H2O

need Vit E/ selenium (selenium is part of glutathione peroxidase), and albumin/ceruloplasmin/transferrin to bind Cu and Fe

Front 28

what causes DNA injury

Back 28

free radicals
- react with thiamine to produce single strand breaks

viruses
- can insert into host cell genome

toxins
- aflatoxin binds to DNA forming adducts

radiation
- UV light forms thymine dimers

Front 29

what interferes with energy supply

Back 29

toxins
- aflatoxin inhibits FA oxidation

Hypoxia
- very impt!
- leads to cell death

Front 30

What inhibits protein synthesis/ damages proteins themselves

Back 30

toxins
- amanita mushroom toxin (inhibits RNA polymerase)
- ricin (inhibits ribosomes)

Heat (and life in general)
- denatures proteins

Front 31

what are the characteristics of heat shock proteins (3)

Back 31

produced in response to cell stress (heat/ anoxia/ viral infections/ toxins)

act intracellularly to recognize/ bind/ chaperone/ refold/ degrade proteins

conserved throughout evolution

Front 32

what is the medical relevance of heat shock proteins

Back 32

autoimmune diseases often target HSP

HSP expression linked to resistance to anti-cancer drugs

increased HSP expression related to survival of anoxia

Front 33

how does aflatoxin affect cells

Back 33

inhibits fatty acid oxidation (results in fatty change)

binds to DNA forming adducts

Front 34

what causes defective fatty acid oxidation

Back 34

anoxia

many toxins (such as aflatoxin)

Front 35

where is fatty infiltration most common

Back 35

heart and pancreas

Front 36

when do you see glycogen accumulation in dogs

Back 36

steroid hepatopathy

Front 37

pathogenesis of canine steroid hepatopathy

Back 37

excess endogenous or exogenous glucocorticoids

-> induction of glycogen synthetase enzyme

-> excess glycogen is produced and accumulates in hepatocyte cytoplasm

-> hepatocyte dysfunction and elevated liver enzymes (esp ALP)

Front 38

know normal fatty acid processing

Back 38

Front 39

Back 39

fatty change

Front 40

Back 40

cat kidney

Front 41

Back 41

dog kidney

Front 42

Back 42

fatty infiltrate

Adipocytes move from epicardium into the heart (usually in R ventricle) (not fatty change b/c it adipocytes infiltrating, not lipid in cardiac cells)

Front 43

Back 43

protein accumulation

rare

eosinophilic cytoplasmic droplets

not impt in vet med

Front 44

what does canine steroid hepatopathy look like

what is the prognosis?

Back 44

Grossly
- liver is enlarged, orange-brown, and friable

Microscopically
- midzonal hepatocytes are swollen with cleared

prognosis
- good

Front 45

causes of glycogen accumulation

Back 45

canine steroid hepatopathy

diabetes mellitus

storage diseases

neonatal animals have abundant glycogen in hepatocytes normally

Front 46

why hepatocyte change is seen in patients with diabetes mellitus

Back 46

glycogen accumulation

often see fatty change as well

Front 47

Back 47

steroid hepatopathy

Pink hepatocytes normal, white ones are the affected ones (glycogen, like fat, is lost in processing)

Zonal pattern

Hazy/ lacy palllor clearing to cytoplasm

No sinusoids b/c cells too swollen that they closed the sinusoids off

Glycogen usually doesn’t displace the nucleus whereas the lipid usually does

Prognosis good b/c injury

Front 48

Back 48

steroid hepatopathy

Pink hepatocytes normal, white ones are the affected ones (glycogen, like fat, is lost in processing)

Zonal pattern

Hazy/ lacy palllor clearing to cytoplasm

No sinusoids b/c cells too swollen that they closed the sinusoids off

Glycogen usually doesn’t displace the nucleus whereas the lipid usually does

Prognosis good b/c injury

Front 49

Back 49

glycogen storage disorder

Congenital enzyme deficiency

One of those can result in glycogen accumulation

More diffuse

Glycogen found in more cells
than just hepatocytes

Front 50

Back 50

diabetes mellitus (glycogen accumulation and fatty change)

Still polygonal cells with nucleus in center

Diabetes can produce both glycogen and fat accumulation in liver

Front 51

Back 51

Front 52

how do aflatoxins cause fatty change?

a. Excess entry
b. Defective oxidation
c. Decreased apoproteins
d. Defective lipoprotein secretion

Back 52

b. Defective oxidation

(toxins can also affect lipoprotein secretion but aflatoxin interferes with oxidation)