Pathology
Table of Contents
HC 2: Cell injury, cell death and adaptations ...................................................................... 1
HC 3: Neoplasia ................................................................................................................ 7
HC 3: Inflammation and repair ........................................................................................ 13
HC 4: Hemodynamic disorders, Thromboembolism and shock ......................................... 22
HC 5: Diseases of the immune system + skin .................................................................... 29
HC 2: Cell injury, cell death and adaptations
Causes of cell injury:
- Hypoxia and ischemia
- Toxins
- Infections
- Abnormal immune reactions
- Genetic abnormalities
o Missense mutation
o Eg. Sickle cell disease
- Nutritional imbalances
- Physical agents
Reversible cell injury:
- When it occurs (bcs of ischemia) the cells start swelling
but also organelles
Irreversible cell injury:
- Inability to restore mitochondrial function
- Altered structure and loss of function of the plasma and intracellular membranes.
- Loss of structural integrity if DNA and chromatin
Cell death:
,- Necrosis
o Due to severe disturbances > such as loss of oxygen,
nutrient supply and the actions of toxins
o Fall apart of cell membrane → leakage of enzymes →
inflammatory reaction.
o 5 Morphologic patterns:
1. Coagulative necrosis
a. Usually secondary to ischemia
b. Injury of structural proteins, but also of
enzymes
c. Wedge shape yellow discoloration, firm
texture
d. Tissue architecture is preserved for at least
days after the injury
e. Over time: recruited leukocytes digest dead
cells
2. Liquefactive necrosis
a. At sites of bacterial: puss, abscess
b. Ischemic necrosis in CNS
c. Finally, removed by phagocytes
d. Microbes stimulate the accumulation of inflammatory cells, and
the enzymes of these leukocytes digest (‘liquefy’) the tissue
e. Loss of architecture
f. Finally, loss of tissue (hole in the brain)
3. Caseous necrosis
a. Tuberculous infections
b. Granulomatous inflammation (A granuloma is an aggregation
of macrophages (along with other cells) that forms in response to
chronic inflammation. This occurs when the immune
system attempts to isolate foreign substances that it is otherwise
unable to eliminate)
i. Obliteration of tissue architecture, cellular outlines
ii. Granular, amorphous, pink cellular debris
iii. Rimmed by macrophages → granuloma formation
c. Looks like French cheese
4. Fat necrosis (saponification)
a. Acute pancreatitis
b. Abdominal trauma
c. Histology: fat cell necrosis, granular basophilic calcium deposits
, 5. Fibrinoid necrosis
a. Immune mediated diseases
b. Deposition of immune complexes
- Apoptosis (programmed cell death)
o Cells activate enzymes that degrade the cells
own nuclear DNA and nuclear cytoplasmic
proteins.
o Causes:
▪ Physiologic conditions
• Area between fingers
▪ Pathologic conditions
• DNA damage
• Viral infections
o 2 pathways
1. Mitochondrial (intrinsic) pathway
a. When mitochondrial membranes
become permeable, cytochrome c
leaks into the cytoplasm, triggering
caspase activation and apoptotic death
b. Permeability of mitochondria is
controlled by a family of more than 20
proteins, of which the prototype is
BCL2
c. BCL2 (and other anti-apoptotic
moleclules) are produced in response
to growth factors and other stimuli
that keep cells viable
d. These antiapoptotic proteins maintain
the integrity of mitochondrial
membranes
e. BH3 is sensor activated upon (A, B, C, D), and shift the balance in
favor of BAX and BAK
2. Death receptor (extrinsic) pathway
a. Death receptors (surface molecules) trigger apoptosis
b. Type 1 TNF receptor (Fas)
o Execution phase
▪ Phagocyte recognizes apoptotic cells
, - Autophagy
Necrosis vs apoptosis
Table of Contents
HC 2: Cell injury, cell death and adaptations ...................................................................... 1
HC 3: Neoplasia ................................................................................................................ 7
HC 3: Inflammation and repair ........................................................................................ 13
HC 4: Hemodynamic disorders, Thromboembolism and shock ......................................... 22
HC 5: Diseases of the immune system + skin .................................................................... 29
HC 2: Cell injury, cell death and adaptations
Causes of cell injury:
- Hypoxia and ischemia
- Toxins
- Infections
- Abnormal immune reactions
- Genetic abnormalities
o Missense mutation
o Eg. Sickle cell disease
- Nutritional imbalances
- Physical agents
Reversible cell injury:
- When it occurs (bcs of ischemia) the cells start swelling
but also organelles
Irreversible cell injury:
- Inability to restore mitochondrial function
- Altered structure and loss of function of the plasma and intracellular membranes.
- Loss of structural integrity if DNA and chromatin
Cell death:
,- Necrosis
o Due to severe disturbances > such as loss of oxygen,
nutrient supply and the actions of toxins
o Fall apart of cell membrane → leakage of enzymes →
inflammatory reaction.
o 5 Morphologic patterns:
1. Coagulative necrosis
a. Usually secondary to ischemia
b. Injury of structural proteins, but also of
enzymes
c. Wedge shape yellow discoloration, firm
texture
d. Tissue architecture is preserved for at least
days after the injury
e. Over time: recruited leukocytes digest dead
cells
2. Liquefactive necrosis
a. At sites of bacterial: puss, abscess
b. Ischemic necrosis in CNS
c. Finally, removed by phagocytes
d. Microbes stimulate the accumulation of inflammatory cells, and
the enzymes of these leukocytes digest (‘liquefy’) the tissue
e. Loss of architecture
f. Finally, loss of tissue (hole in the brain)
3. Caseous necrosis
a. Tuberculous infections
b. Granulomatous inflammation (A granuloma is an aggregation
of macrophages (along with other cells) that forms in response to
chronic inflammation. This occurs when the immune
system attempts to isolate foreign substances that it is otherwise
unable to eliminate)
i. Obliteration of tissue architecture, cellular outlines
ii. Granular, amorphous, pink cellular debris
iii. Rimmed by macrophages → granuloma formation
c. Looks like French cheese
4. Fat necrosis (saponification)
a. Acute pancreatitis
b. Abdominal trauma
c. Histology: fat cell necrosis, granular basophilic calcium deposits
, 5. Fibrinoid necrosis
a. Immune mediated diseases
b. Deposition of immune complexes
- Apoptosis (programmed cell death)
o Cells activate enzymes that degrade the cells
own nuclear DNA and nuclear cytoplasmic
proteins.
o Causes:
▪ Physiologic conditions
• Area between fingers
▪ Pathologic conditions
• DNA damage
• Viral infections
o 2 pathways
1. Mitochondrial (intrinsic) pathway
a. When mitochondrial membranes
become permeable, cytochrome c
leaks into the cytoplasm, triggering
caspase activation and apoptotic death
b. Permeability of mitochondria is
controlled by a family of more than 20
proteins, of which the prototype is
BCL2
c. BCL2 (and other anti-apoptotic
moleclules) are produced in response
to growth factors and other stimuli
that keep cells viable
d. These antiapoptotic proteins maintain
the integrity of mitochondrial
membranes
e. BH3 is sensor activated upon (A, B, C, D), and shift the balance in
favor of BAX and BAK
2. Death receptor (extrinsic) pathway
a. Death receptors (surface molecules) trigger apoptosis
b. Type 1 TNF receptor (Fas)
o Execution phase
▪ Phagocyte recognizes apoptotic cells
, - Autophagy
Necrosis vs apoptosis
