Njds Pathology - Cellular Pathology Iii: Cell Injury

Front 1

Intracellular target of injurious stimuli and their consequences

Back 1

1. Mitochondria - disruption in aerobic respiration

2. Cell membranes - disruption in ionic and osmotic hemostasis and lysosome rupture

3. RER and ribosome - disruption in protein synthesis

4. Genetic apparatus - degradation and disruption of DNA

Front 2

Effects of acute hypoxia on intracellular systems

Back 2

1. Na pump failure ⇒ ↑ intracellular Na ⇒ ↑ H2O

2. Ca pump failure ⇒ ↑ intracellular Ca ⇒ ↑ activation of degrading enzymes

3. ↑ anaerobic glycolysis ⇒ ↓ glycogen, ↑ lactic acid, ↓ pH

4. ribosome detachment ⇒ ↓ protein synthesis

Restoring O2 may reverse initial effects of acute hypoxia

Front 3

What are the morphological change of cells in acute hypoxia?

Back 3

1. Microscopically, cells appear enlarged, swollen, and vacuolated. Vacuoles represent distended/dilated RER and mitochondria

2. Grossly, organs appear swollen, tense, heavy, and pale

Front 4

Mechanisms that contribute to membrane damage include...

Back 4

1. Mitochondrial dysfunction
2. Damage to cytoskeleton
3. Loss of membrane phospholipids
4. Accumulation of phopholipid degradation products
5. Generation of reactive O2

Front 5

Mycardial infarction can be detected how?

Back 5

↑ serum levels of MB isoenzymes of creatine kinase and cardiac troponin I and T is detected from dying cells

Front 6

Reactive Oxygen Species (ROS)

Back 6

1. Attack and degrade membrane lipids, DNA, and proteins

2. Generated from electron and oygen transport systems where O2 is reduced to H2O

Front 7

Reactive oxygen species are generated under what circumstances?

Back 7

1. O2 toxicity (O2 therapy)

2. Radiation (e.g. UV rays, x-rays)

3. Chemical/drug induced tissue injury (e.g. CCL4, acetominophen)

4. Presence of xanthne in reperfused (restoration of blood flow after ischemia) hypoxic tissues which causes radicals ⇒ xanthine oxidase inhibitors prevent toxic oxygen metabolites

5. Microbial killing by neutrophils and macrophages during inflammation

Front 8

Free radical scavengers

Back 8

1. Antioxidants

2. Enzymes such as catalase, superoxide dismutase and glutathione peroxidase

Front 9

Necrosis

Back 9

1. Unintentional or accidental cell death

2. Caused by pathological injury resulting in necrosis from degradative enzymes.

3. Autolysis - degradative enzymes that come from the dead cells themselves

4. Hemolysis - degradative enzymes coming from inflammatory cells like neurotphils and macrophages

5. Degradative enzymes cause DIGESTION of cellular structures and DENATURATION of proteins

Front 10

T/F: Necrosis and apoptosis are synonomous.

Back 10

FALSE: Necrosis involves area of many dead cells whereas apoptosis includes only a single or few cells

Front 11

What do necrotic cells look like?

Back 11

Nuclear changes

1. PYKNOSIS - shrunken nucleus that becomes basophilic (due to cessation of DNA txn)

2. KARYORRHEXIS - nucleus breaks up into frgaments

3. KARYOLYSIS - nucleus undergoes dissolution and disappears.

Cytoplasmic changes

1. ↓ basophilia and ↑ eosinophilia

2. Shrinkage of cellular plasma membrane

3. Presence of MYELIN FIGURES (large whorled masses of phopholipids) that replace dead cells

Front 12

Coagulative necrosis

Back 12

1. "Cooked meat" - firm and pale

2. Appearance due to denaturation of intrinsic structural and enzymative cell proteins

3. Microscopically, cell outline and architecture is intact for a few days but later becomes anuclueate with pink cytoplasm and homogenous

4. Common pattern of necrosis in hypoxic induced cell death EXCEPT the brain

Front 13

Liquefactive necrosis

Back 13

1. "Pudding" - soft and semi-liquid

2 Due to powerful hydrolytic enzymes

3. Microscopically, cellular architecture is obliterated and is replaced by neutrophils and tissue debris

4. Develops in hypoxic brain cell death in PYGOGENIC bacterial infections (Staphylococcus aureus, neisseria gonorrrhoeae, chlamydia tracomatis)

5. Clinically referred to as pus.

Front 14

Caseous necrosis

Back 14

1. "Dry parmesan cheese" - crumbly, soft, and white

2. Combination of denaturation and cell digestion

3. Cell outline and architecture is obliterated and contains pink, granular, amorphous debris

4. Is pathognomonic (characteristic of a specific disease) for TB

Front 15

Fat Necrosis

Back 15

1. "Droplets of wax" - appears yellow or chalky white

2. Microscopically appears like smudgy shadows w/o nuclei

3. Occurs in pancreatitis where digestive enzymes (lipase) of injured acinar cells liquefy fat cells of the omentum

4. FAT SAPONIFICATION - process where fatty acids combine with calcium to form calcium soaps

Front 16

Gangrenous Necrosis (gangrene)

Back 16

1. Dry gangrene - dried and shriveled necrotic tissue that has undergone coagulative necrosis due to ischemia

2. Wet gangrene - secondary bacterial infection + associated liquefactive necrosis superimposed on dry gangrene

3. Gas gangrene - gangrene associated with anaerobic bacteria (e.g. chlostridium perfringens) that cause gas bubbles in necrotic tissue

Front 17

Liquefactive necrosis

Back 17

1. Due to powerful hydrolytic enzymes

2. Grossly appears to be soft and semi-liquid like pudding

3. Microscopically, cellular architecture is obliterated and is replaced by neutrophils and tissue debris

4. Develops in hypoxic brain cell death in PYGOGENIC bacterial infections (Staphylococcus aureus, neisseria gonorrrhoeae, chlamydia tracomatis)

5. Clinically referred to as pus.

Front 18

Apoptosis

Back 18

1. Programmed intentional cell death

2. Single or small clusters of cells shrink away from surrounding cells with loss of cell surface specialization

3. "Boils" appearance from blebs on cell surface

4. "Crescents" of condensed nuclear chromatin appear and undergo karyorrhexis

5. Cytoplasm intensely eosinophilic

6. "Apoptotic bodies" - membrane bounded fragments of apoptotic cell that are phagocytosed by neighboring cells

7. DOES NOT elicit inflammatory response like necrosis

Front 19

Physiological and pathological examples of apoptosis

Back 19

Physiological

1. Loss of digital webbing in embryogenesis

2. Thymic involution during young adulthood

3. Shedding of skin and mucosal epithelia during normal turnover

Pathological

1. Apoptosis of virally infected cells

2. Apoptosis in cardiac myocytes in mycardial infarcation and heart failure

Front 20

Apoptosis

Back 20

1. Programmed intentional cell death

2. Single or small clusters of cells shrink away from surrounding cells with loss of cell surface specialization

3. "Boils" appearance from blebs on cell surface

4. "Crescents" of condensed nuclear chromatin appear and undergo karyorrhexis

5. Cytoplasm intensely eosinophilic

6. "Apoptotic bodies" - membrane bounded fragments of apoptotic cell that are phagocytosed by neighboring cells

7. DOES NOT elicit inflammatory response like necrosis

Front 21

Signalling of apoptosis

Back 21

1. Initiation by ligand binding to TNF "death receptor" (internal pathway) or mitochondria release of cytochrome C causing activating of caspase cascade (the "execution caspases)

DEF: Caspase - proteases that mediate apoptosis

2. Regulated by BCL-2 family proteins: BAD, BAK, BAX promote apoptosis and BCL-2 and BCL-X inhibit apoptosis

3. Failure of normal apoptosis can lead to cancer (e.g. over-expression of BCL-2 in lymphoma can lead to dysregulated cell proliferation)

Front 22

T/F: Myelin figures appear in cells that have undergone apoptosis.

Back 22

FALSE: Myelin figures only appear in cells that have undergone UNINTENTIONAL cell death