Cell and Tissue Injury

Question 1

1. Discuss major causes (etiologies) of cell injury.
2. Describe how cell injury contributes to the pathogenesis of disease.
3. Identify major mechanisms of cell injury.
4. Identify how the study of morphologic change caused by cell injury explains the whys and wherefores of signs and symptoms of disease.
5. Identify free radicals, how they arise, how they produce cell injury and how the body gets rid of them.
6. Describe how ischemia/hypoxia creates a setting where free radical damage becomes an important cause of cell injury.
7. Compare and contrast necrosis and apoptosis.
8. Describe the adaptations associated with chronic injury.
9. Identify the major alterations in the cell membrane, mitochondrion and nucleus that occur during cell injury.
10. Describe the four major types of necrosis seen in human disease.
11. Identify the reversible and irreversible morphologic and biochemical alterations during hypoxic injury.

Answer 1

x

Question 2

_____ is the most common tissue type injured in human disease.

Answer 2

Epithelium (vs muscle, nerve, connective)

Question 3

Chronic vs acute injury can be differentiated by viewing what in a histological section?

Answer 3

The nature (cell types) of the exudate.

Acute - PMN
Chronic - lymphocytes/macrophages

Question 4

What four cellular structures are easily injured?

Answer 4

1. Plasma membrane
2. Mitochondria
3. ER
4. Nucleus

Question 5

3 classic examples of reversible cell injury

Answer 5

1. cell swelling (results from inc. h20 permeability)
2. increase in extracellular metabolite (eg diabetes)
3. Fatty change (accum. of fat due to many types of injury)

Question 6

4 examples of cellular adaptation

Answer 6

1. hypertrophy
2. atrophy
3. metaplasia
4. hyperplasia

Question 7

Causes of cell atrophy (4)

Answer 7

1. loss of blood supply
2. loss of endocrine factors (eg TSH)
3. Decrease in workload
4. aging, chronic illness

Question 8

Coagulative necrosis is seen where? What is the appearance?

Answer 8

Classically seen in heart attack. Dead cell still retains shape. Looks like a “ghost like remnant” of its former self. Will often see pyknosis -

Question 9

What two pathologic signs indicade cell death?

Answer 9

Pyknosis - nucleus is shrunken, and intensely dark staining (can be seen in apoptosis as well).
Karyorrhexis -
Karyolysis - hydrolysis of nucleus

Question 10

Liquefactive Necrosis

Answer 10

Lysosomal hydrolases from neutrophils? m

Question 11

Caseous necrosis (Case-ee-ous)

Answer 11

Tuberculosis. Tissues become soft, whitish grey (resembles milk protein casein, hence the name)

Question 12

Fat necrosis

Answer 12

Typically occurs in the pancreas during acute injury. LIpases from dead cells degrade nearby free fatty acids.

Question 13

What is metaplasia?

Answer 13

Replacement of one cell type with another. Example: chronic acid reflux changes stratified squamous epithelium into a columnar.

Question 14

What is hyperplasia?

Answer 14

an increase in the number of cells of a tissue in response to a stimulus or injury. Example: increase in the number of adrenal cortical cells secondary to a tumor that produces an ACTH- like polypeptide.

Question 15

Hypoxia vs ischemia

Answer 15

Hypoxia - tissue receiving inadequate oxygen

Ischemia - related to inadequate blood supply

Question 16

Hypoxic injury induces what? (Step 1 favorite)

Answer 16

HIF1alpha which upregulates EPO, VEGF, glucose transporters, gycolytic enzymes

Question 17

Ischemia will first affect the mitochondria. Within 1 minute of O2 deprivation, the ATP levels will fall to 10% of normal. The switch to glycolysis decreases pH within the cell. Lack of ATP causes increased sodium leakage. Protein synthesis decreases. Are these changes reversible?

Answer 17

Yes.

Question 18

After continued O2 deprivation, hypoxic injury becomes irreversible. What are three examples?

Answer 18

1. MPTP (mitochondrial permeability transition pore). If unable to close this, cell death via necrosis may be unavoidable.
2. Activation of lysosomal enzymes
3. Degradation of DNA and protein
4. Influx of Ca++ (remember ECF/ICF conc. of Ca) causes activation of all manner of enzyme pathways via signaling pathways–> curtains for the cell

Question 19

Hypoxic patients are given O2. What is the problem with this treatment?

Answer 19

High O2 actually damages cells (particularly alveolar cells) because higher levels of ROS are created. Electrons in outer orbital of O are easily lost, creating an Oxygen radical.

Question 20

What are two ways ROS are introduced into cells?

Answer 20

PMNs, reperfusion…..see slide.

Question 21

SOD

Answer 21

Superoxide dismutase (sp?) Make H2O2 (peroxide).

Question 22

H2O2 can cause problems in what ways

Answer 22

1. formation of OH radical (3 unpaired electrons very bad)
2. Fenton rxn (Fe++ –> Fe+++ plus OH radical)
3. Haber weiss rxn (H2O2 + O2 –> OH radical)

Question 23

Cell injury/repair resulting from burns depends on what factors?

Answer 23

1. Total surface area of burn
2. Depth of burn
3. Damage to lungs
4. Timeliness of treatment

Question 24

What is the importance of hair follicles regarding burns?

Answer 24

Preservation of hair follicles in a partial thickness burn preserves stem cells present in the hair follicles, which allows repair. Full thickness burn requires a skin graft.

Question 25

What are some complications of burns?

Answer 25

Neurogenic shock
infection
hypermetabolic state (must increase calorie intake dramatically)
fluid loss
anemia (bone marrow stops producing)

Question 26

Exertional heat stroke

Answer 26

Hot, dry skin
Lactic acidosis
May lead to acute kidney injury, Disseminated Intravascular Coagulation (DIC), organ failure, death

Question 27

Classic Heat stroke

Answer 27

Hot dry skin
No lactic acidosis, but respiratory alkalosis due to hyperventilation
DIC/ATN uncommon
Hypotension, coma

Question 28

Hypothermic injury

Answer 28

Brain metabolism inadequate
Poor perfusion of tissues (digits) b/c increased viscosity of blood, vasoconstriction
Freezing of cells can increase local salt concentrations