Cell Injury, Adaptation And Death

Front 1

Differentiate between hypertrophy, atrophy and hyperplasia and metaplasia

Back 1

Hyperplasia--> increase in number of cells (ex. Cushing's disease = adrenal cortex hyperplasia)

Hypertrophy-->

*CNS and muscle cannot undergo hyperplasia because they are stuck in G0 phase

Atrophy-->decrease in cell size (reversible) and or cell # (cell death)

Metaplasia--> Change in the cell type in response to different cellular stress (ex 1. GERD--> Esophageal cells replaced by goblet cells.

Ex 2. smoking--> replacement of pseduostrat columnar with squamous epithelium

Dysplasia--> Prolonged metaplasia (--> Cancer)

Front 2

What are the consequences of ATP depletion secondary to cell damage?

Back 2

Reduction in ATP-dependent Sodium pump:

Anaerobic glycolysis:

Altered metabolism:

Calcium influx:

Front 3

Reduction in ATP-dependent Sodium pump:

Back 3

Reduction in ATP-dependent Sodium pump: Na+/K+ ATPase pumps 3 NA+ out and brings 2 K+ in (Net loss of 1 ion) If pump work is reduced. There is a net increase of solute within the cell, which leads to cellular swelling.

Front 4

Anaerobic glycolysis:

Back 4

Anaerobic glycolysis: There is a compensatory increase in anaerobic metabolism in an attempt to maintain the cell’s energy sources.

As a consequence, intracellular glycogen stores depletion and lactic acid accumulation

Leads to decreased intracellular pH and decreased activity of many cellular enzymes. And will eventually cause chromatin clumping

Front 5

Altered metabolism:

Back 5

Can occur due to hypoxia (resulting in an increase in anaerobic metabolism) which eventually leads to chromatin clumping.

Can also occur due to toxic injury. Ex. Fatty change (steatosis): An abnormal accumulation of triglycerides within parenchymal cells (mostly in liver). You will start seeing lipid vacuoles developing in the cell.

Front 6

Calcium influx:

Back 6

Intracellular calcium is usually maintained at a much lower concentration than extracellular calcium by ATP-dependent calcium transporters.ATP depletion ---> Ca pump can’t maintain low concentration inside cell -----> Ca increase activate a number of proteins that can damage the cell (which may lead to apoptosis).

Front 7

Mitochondrial damage:

Back 7

Mitochondria are sensitive to many types of injurious stimuli, including hypoxia, chemical toxins, and radiation. Damage results in several biochemical abnormalities including failure of oxidative phosphorylation and progressive ATP depletion, activation of apoptosis.

Front 8

Image of Fatty change

Back 8

Front 9

What are the predictors of reversible vs. Irreversible cellular damage/change?

Back 9

Cell swelling and fatty change is commonly seen as first steps in cell injury and are considered as the main morphologic correlation to reversible cell injury

Prolonged cell injury that initially cause reversible cell injury can eventually progress to irreversible cell injury.

Indications that help us to identify irreversible injuries are: Nuclear changes, disruptions of cellular membranes and fragmentations.

Front 10

What are the key histological changes in irreversible cell death?

Back 10

Necrotic cells may have a more glassy homogeneous appearance due to loss of glycogen (allegedly visible on the above image according to Robbins)

Necrotic cells may be replaced by myelin figures, which are large, spiral-looking phospholipid masses-

Nuclear changes: (1) pyknosis means nuclear shrinkage and increased basophilia (also seen in apoptosis)

(2) karyoorhexis means the pyknotic nucleus undergoes fragmentation (over time, nucleus disappears)

(3) karyolysis means fading of chromatin basophilia (less blue) due to degradation of DNA by endonucleases

Front 11

What are the different types of necrosis and with what are they associated?

Back 11

Infarcts in CNS are often liquefactive necrosis!

Front 12

Back 12

Coagulative Necrosis

Front 13

Back 13

Liquefactive Necrosis

Front 14

Back 14

Fat necrosis

Front 15

Back 15

Fibrinoid necrosis

Front 16

Back 16

Casesous necrosis

Front 17

What are the key features of apoptosis?

Back 17

Apoptosis is not associated with ATP depletio

Apoptosis is the result of unresolved autophagy

Apoptosis is a normal way of clearing old or unnecessary cells;

No inflammatory reaction-if DNA or proteins are damaged, pathogenesis may result in apoptosis

Front 18

Distinguish apoptosis from necrosis.

Back 18

Front 19

Draw the flowchart of possible events that can occur as a result of increased or changes in cell stress

Back 19

Front 20

Back 20

Abcess liquifactive necrosis around it with lots of immune cells

Front 21

Back 21

Fat necrosis in pancreas.

Front 22

Back 22

Caseating granulomatous necrosis

Front 23

Back 23

Enough said

Front 24

Back 24

Enough said

Front 25

What are the consequences of ATP deprivation in cells?

Back 25

Front 26

Back 26

Intimal hypertrophy

Front 27

Back 27

Metaplasia response to smoking

Front 28

Describe the process of Necrosis

Back 28

Front 29

Contrast the process of apoptosis and necrosis

Back 29

Front 30

Overall flowchart of how cells respond to stress or injury

Back 30