BSc Biomedical Sciences (VU Amsterdam) Pathology Active Recall
Not your usual “Notes” - How to use this to REWIRE your BRAIN:
▪ Bullet-point Question/Answer format
▪ Based on Chapters from Robbins “Basic Pathology”, 11th Edition (Chap 1, 2, 3, 5,
6, 8, 9, 10, 11, 13, 17, 21 and 22)
▪ Colour the questions RED until you perfect them. Colour them GREEN once you’ve
mastered them. Then, ONLY practice the red question, until they’re all green.
▪ Follow the chapters from the book to view images and visuals corresponding to the
notes.
Chapter 1: Cell injury, cell death and adaptations
● What is pathology? Study of causes of diseases and associated changes to cells,
tissues and organs.
● What is Etiology? Origin of a disease - underlying causes.
● What is Pathogenesis? Steps in development of a disease from etiologic trigger to
cellular changes that give rise to abnormalities.
● When does cell injury occur? Usually the cell can adapt to changing conditions and
maintain homeostasis. But when adaptive capability is exceeded or external stress is
harmful, cell injury occurs. Cell injury is reversible.
● When does cell death occur? Persistent stress causes cell death.
● What are the example causes of cell injury? Hypoxia (less O2 to cells), toxins,
infectious agents (viruses, bacteria, fungi), autoimmune reactions, genetic
abnormalities, nutritional imbalances, and physical agents (temperature, radiation,
electric shock)
● What are the features of reversible cell injury? Can recover if damaging stimulus is
removed. 1) Cellular swelling: Organelles in the cell become swollen as they take in
water. 2) Some cells also have some lipid vacuoles accumulate in them.
● What can cell injury depend on? Cell type (for example skeletal muscle survives
ischemia longer than cardiac muscle)
● What are the 2 ways in which cell death can occur? Necrosis and Apoptosis.
● What is Necrosis? “Accidental cell death” caused by severe circumstances beyond
salvage.
● What is Apoptosis? Relies on defined genes and biochemical pathways - very
controlled and “regulated” cell death. Unlike necrosis, it also occurs in healthy tissues
and not necessarily related to pathological cell injury.
● Cell death often happens long after the cell has actually stopped working.
Necrosis
● What are some key features of necrosis? Cell membranes break down, Cell contents
leak out, Enzymes digest the cell and Inflammation always happens
,● Why does inflammation happen in necrosis? Dead cells release substances that trigger
the host response called inflammation. Inflammation removes dead debris, recruits
leukocytes and begins tissue repair
● Where do enzymes digesting necrotic cells come from? From Leukocytes recruited
during inflammation, and also from Lysosomes inside the dying cell itself
● What are some of the morphological changes you see in necrosis?
○ Cytoplasmic changes
○ Nuclear changes
● What are the cytoplasmic changes in necrotic cells?
Increased eosinophilia (pink staining) —> necrotic cells look more pink because
proteins get denatured and bind eosin dye more. Also, RNA is lost, so less basophilia
(blue staining)
Glassy homogenous appearance → due to loss of glycogen particles
Vacuolated “moth eaten” cytoplasm → organelles are digested so holes appear
● What are nuclear changes in necrotic cells? All due to DNA/chromatin breakdown
○ Pyknosis → nucleus shrinks, chromatin condenses, very dark nucleus
○ Karyorrhexis → nucleus fragments
○ Karyolysis → nucleus fades away, DNA digested by DNases
○ Within 1 - 2 days, the nucleus completely disappears.
● What are morphological patterns of tissue necrosis?
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
● What is coagulative necrosis? Tissue architecture preserved for days, firm texture,
proteolysis slowed - often due to ischemia and in all solid organs except the brain
● What is liquefactive necrosis? Tissue completely digested → liquid mass, common in
infections since leukocytes release enzymes. Seen in bacterial/fungal infections, or
ischemic necrosis in brain. Often pus seen → Abscess (localised pus collection)
● What is gangrenous necrosis? Can be dry or wet. Dry gangrene: limb ischemia →
coagulative necrosis. Wet gangrene: infection added → liquefactive destruction
● What is caseous necrosis? Classic for TBC. Yellow-white cheese like area. Is
granulomatous
● What is fat necrosis? Caused by trauma or acute pancreatitis. Pancreatic enzymes
digest fat → fatty acids released. Fatty acids + calcium → chalky white deposits
(saponification)
● What is fibrinoid necrosis? Immune-mediated disease. Visible only microscopically.
Immune complexes + plasma proteins leak into vessel wall → bright pink fibrin-like
appearance.
● What are clinical markers of necrosis?
Troponin → myocardial infarction
, AST/ALT → hepatocyte injury
Alk phosphatase → bile duct damage
Apoptosis
● What are the key differences of apoptosis from necrosis? membrane remains intact,
cell fragments into apoptotic bodies, phagocytosed quickly, and no inflammation
● What are the two kinds of apoptosis? Physiological apoptosis and Pathologic
apoptosis
● What is physiological apoptosis? Normal and beneficial. Embryonic development,
removal of excess immune cells, deletion of self-reactive lymphocytes, etc.
● What is pathologic apoptosis? Triggered when damage is beyond repair. For example,
severe DNA damage (radiation, chemo), misfolded protein accumulation (ER stress),
viral infections
● What are the mechanisms of apoptosis? Intrinsic pathway and extrinsic pathway.
● What is the intrinsic (miropchondrial) pathway for apoptosis? Its the most common
pathway. Triggered from inside the cell by; growth factor withdrawal, DNA damage
and misfolded proteins → explain the pathway
● How does the intrinsic apoptosis pathway work? Stress activates BH3-only proteins.
BH3 inhibits BCL-2 proteins (which normally are anti-apoptotic). BAX and BAK get
activated and dimerise to make pores in mitochondria. Mitochondria leaks out
cytochrome c → activates caspase-9
● What is the extrinsic apoptosis pathway? Triggered from outside the cell, key
receptors are Fas (CD95) and TNF receptor.
● How does the extrinsic (death receptor) pathway work?
Fas ligand binds Fas receptor - “time to die”. Proteins recruited and caspase 8 is
activated.
● What is the terminal phase of apoptosis? Caspases degrade proteins, cytoskeleton and
nucleus. Cell breaks into apoptotic bodies (nuclear fragmentation)
● What is the final clearance phase of apoptosis? Apoptotic cells display “eat-me”
signals. phosphatidylserine flips outward, macrophages engulf fragments rapidly, no
inflammation remains
● What happens in lymphoma? Overactive BCL-2 gene, meaning less apoptosis in the
cancer.
Autophagy
● What is autophagy? “Self-eating” → lysosomal digestion of cell components.
● What is the purpose of autophagy? Survival during starvation.
● How does autophagy work? organelles enclosed in double membrane
(autophagosome), fuses with lysosome → autophagolysosomal, contents digested +
recycled
● Where is autophagy seen? Ischemia, myopathies, infections (kills microbes)
● If stress continues → autophagy may lead to apoptosis.
● Cancer cells often survive stress without autophagy.
Major mechanisms of cell injury
● What are the main mechanisms of cell injury?
Mitochondrial dysfunction
, ROS injury (Oxidative stress)
Membrane damage
Calcium influx
ER stress
DNA damage and p53
● Why does mitochondrial dysfunction cause cell injury? Main consequence: ↓ ATP
ATP depletion causes:
Na/K pump failure → Na + water influx → swelling
anaerobic glycolysis → lactic acidosis → ↓ pH
ribosome detachment → ↓ protein synthesis
membrane rupture → necrosis
Mitochondrial permeability transition pore opens → collapse of function.
Cytochrome c release → apoptosis.
● Why does ROS cause cell injury?
Reactive oxygen species damage cells.
Produced by: mitochondria during respiration and leukocytes during respiratory burst
Main ROS: superoxide (O2•–), hydrogen peroxide (H2O2), hydroxyl radical (•OH)
Radiation increases ROS via water hydrolysis.
● Why does membrane damage lead to cell injury and cell necrosis? Causes:
ROS
↓ phospholipid synthesis
↑ phospholipid breakdown (Ca activation)
cytoskeletal disruption
Key sites:
mitochondria
plasma membrane
lysosomes → enzyme leakage → autodigestion
● How does calcium influx cause cell injury? Normal cytosolic Ca is very low.
Ischemia/toxins → Ca rises due to:
ER/mitochondria release
plasma membrane leak
Excess Ca activates: proteases, phospholipases, endonucleases → cell destruction
● How does ER stress cause cell injury? Misfolded proteins accumulate → UPR
activated. Adaptive response:
↑ chaperones
↓ protein translation
If too much stress → apoptosis (intrinsic pathway)
Seen in: aging, viral infections, ischemia, cystic fibrosis
● How does DNA damage and p53 cause cell injury? DNA damage triggers
accumulation of p53: which can arrest the cell or lead to apoptosis.
arrests cell cycle at G1 → repair.
if damage severe → apoptosis
If p53 mutated → damaged cells survive → cancer transformation
Not your usual “Notes” - How to use this to REWIRE your BRAIN:
▪ Bullet-point Question/Answer format
▪ Based on Chapters from Robbins “Basic Pathology”, 11th Edition (Chap 1, 2, 3, 5,
6, 8, 9, 10, 11, 13, 17, 21 and 22)
▪ Colour the questions RED until you perfect them. Colour them GREEN once you’ve
mastered them. Then, ONLY practice the red question, until they’re all green.
▪ Follow the chapters from the book to view images and visuals corresponding to the
notes.
Chapter 1: Cell injury, cell death and adaptations
● What is pathology? Study of causes of diseases and associated changes to cells,
tissues and organs.
● What is Etiology? Origin of a disease - underlying causes.
● What is Pathogenesis? Steps in development of a disease from etiologic trigger to
cellular changes that give rise to abnormalities.
● When does cell injury occur? Usually the cell can adapt to changing conditions and
maintain homeostasis. But when adaptive capability is exceeded or external stress is
harmful, cell injury occurs. Cell injury is reversible.
● When does cell death occur? Persistent stress causes cell death.
● What are the example causes of cell injury? Hypoxia (less O2 to cells), toxins,
infectious agents (viruses, bacteria, fungi), autoimmune reactions, genetic
abnormalities, nutritional imbalances, and physical agents (temperature, radiation,
electric shock)
● What are the features of reversible cell injury? Can recover if damaging stimulus is
removed. 1) Cellular swelling: Organelles in the cell become swollen as they take in
water. 2) Some cells also have some lipid vacuoles accumulate in them.
● What can cell injury depend on? Cell type (for example skeletal muscle survives
ischemia longer than cardiac muscle)
● What are the 2 ways in which cell death can occur? Necrosis and Apoptosis.
● What is Necrosis? “Accidental cell death” caused by severe circumstances beyond
salvage.
● What is Apoptosis? Relies on defined genes and biochemical pathways - very
controlled and “regulated” cell death. Unlike necrosis, it also occurs in healthy tissues
and not necessarily related to pathological cell injury.
● Cell death often happens long after the cell has actually stopped working.
Necrosis
● What are some key features of necrosis? Cell membranes break down, Cell contents
leak out, Enzymes digest the cell and Inflammation always happens
,● Why does inflammation happen in necrosis? Dead cells release substances that trigger
the host response called inflammation. Inflammation removes dead debris, recruits
leukocytes and begins tissue repair
● Where do enzymes digesting necrotic cells come from? From Leukocytes recruited
during inflammation, and also from Lysosomes inside the dying cell itself
● What are some of the morphological changes you see in necrosis?
○ Cytoplasmic changes
○ Nuclear changes
● What are the cytoplasmic changes in necrotic cells?
Increased eosinophilia (pink staining) —> necrotic cells look more pink because
proteins get denatured and bind eosin dye more. Also, RNA is lost, so less basophilia
(blue staining)
Glassy homogenous appearance → due to loss of glycogen particles
Vacuolated “moth eaten” cytoplasm → organelles are digested so holes appear
● What are nuclear changes in necrotic cells? All due to DNA/chromatin breakdown
○ Pyknosis → nucleus shrinks, chromatin condenses, very dark nucleus
○ Karyorrhexis → nucleus fragments
○ Karyolysis → nucleus fades away, DNA digested by DNases
○ Within 1 - 2 days, the nucleus completely disappears.
● What are morphological patterns of tissue necrosis?
Coagulative necrosis
Liquefactive necrosis
Gangrenous necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
● What is coagulative necrosis? Tissue architecture preserved for days, firm texture,
proteolysis slowed - often due to ischemia and in all solid organs except the brain
● What is liquefactive necrosis? Tissue completely digested → liquid mass, common in
infections since leukocytes release enzymes. Seen in bacterial/fungal infections, or
ischemic necrosis in brain. Often pus seen → Abscess (localised pus collection)
● What is gangrenous necrosis? Can be dry or wet. Dry gangrene: limb ischemia →
coagulative necrosis. Wet gangrene: infection added → liquefactive destruction
● What is caseous necrosis? Classic for TBC. Yellow-white cheese like area. Is
granulomatous
● What is fat necrosis? Caused by trauma or acute pancreatitis. Pancreatic enzymes
digest fat → fatty acids released. Fatty acids + calcium → chalky white deposits
(saponification)
● What is fibrinoid necrosis? Immune-mediated disease. Visible only microscopically.
Immune complexes + plasma proteins leak into vessel wall → bright pink fibrin-like
appearance.
● What are clinical markers of necrosis?
Troponin → myocardial infarction
, AST/ALT → hepatocyte injury
Alk phosphatase → bile duct damage
Apoptosis
● What are the key differences of apoptosis from necrosis? membrane remains intact,
cell fragments into apoptotic bodies, phagocytosed quickly, and no inflammation
● What are the two kinds of apoptosis? Physiological apoptosis and Pathologic
apoptosis
● What is physiological apoptosis? Normal and beneficial. Embryonic development,
removal of excess immune cells, deletion of self-reactive lymphocytes, etc.
● What is pathologic apoptosis? Triggered when damage is beyond repair. For example,
severe DNA damage (radiation, chemo), misfolded protein accumulation (ER stress),
viral infections
● What are the mechanisms of apoptosis? Intrinsic pathway and extrinsic pathway.
● What is the intrinsic (miropchondrial) pathway for apoptosis? Its the most common
pathway. Triggered from inside the cell by; growth factor withdrawal, DNA damage
and misfolded proteins → explain the pathway
● How does the intrinsic apoptosis pathway work? Stress activates BH3-only proteins.
BH3 inhibits BCL-2 proteins (which normally are anti-apoptotic). BAX and BAK get
activated and dimerise to make pores in mitochondria. Mitochondria leaks out
cytochrome c → activates caspase-9
● What is the extrinsic apoptosis pathway? Triggered from outside the cell, key
receptors are Fas (CD95) and TNF receptor.
● How does the extrinsic (death receptor) pathway work?
Fas ligand binds Fas receptor - “time to die”. Proteins recruited and caspase 8 is
activated.
● What is the terminal phase of apoptosis? Caspases degrade proteins, cytoskeleton and
nucleus. Cell breaks into apoptotic bodies (nuclear fragmentation)
● What is the final clearance phase of apoptosis? Apoptotic cells display “eat-me”
signals. phosphatidylserine flips outward, macrophages engulf fragments rapidly, no
inflammation remains
● What happens in lymphoma? Overactive BCL-2 gene, meaning less apoptosis in the
cancer.
Autophagy
● What is autophagy? “Self-eating” → lysosomal digestion of cell components.
● What is the purpose of autophagy? Survival during starvation.
● How does autophagy work? organelles enclosed in double membrane
(autophagosome), fuses with lysosome → autophagolysosomal, contents digested +
recycled
● Where is autophagy seen? Ischemia, myopathies, infections (kills microbes)
● If stress continues → autophagy may lead to apoptosis.
● Cancer cells often survive stress without autophagy.
Major mechanisms of cell injury
● What are the main mechanisms of cell injury?
Mitochondrial dysfunction
, ROS injury (Oxidative stress)
Membrane damage
Calcium influx
ER stress
DNA damage and p53
● Why does mitochondrial dysfunction cause cell injury? Main consequence: ↓ ATP
ATP depletion causes:
Na/K pump failure → Na + water influx → swelling
anaerobic glycolysis → lactic acidosis → ↓ pH
ribosome detachment → ↓ protein synthesis
membrane rupture → necrosis
Mitochondrial permeability transition pore opens → collapse of function.
Cytochrome c release → apoptosis.
● Why does ROS cause cell injury?
Reactive oxygen species damage cells.
Produced by: mitochondria during respiration and leukocytes during respiratory burst
Main ROS: superoxide (O2•–), hydrogen peroxide (H2O2), hydroxyl radical (•OH)
Radiation increases ROS via water hydrolysis.
● Why does membrane damage lead to cell injury and cell necrosis? Causes:
ROS
↓ phospholipid synthesis
↑ phospholipid breakdown (Ca activation)
cytoskeletal disruption
Key sites:
mitochondria
plasma membrane
lysosomes → enzyme leakage → autodigestion
● How does calcium influx cause cell injury? Normal cytosolic Ca is very low.
Ischemia/toxins → Ca rises due to:
ER/mitochondria release
plasma membrane leak
Excess Ca activates: proteases, phospholipases, endonucleases → cell destruction
● How does ER stress cause cell injury? Misfolded proteins accumulate → UPR
activated. Adaptive response:
↑ chaperones
↓ protein translation
If too much stress → apoptosis (intrinsic pathway)
Seen in: aging, viral infections, ischemia, cystic fibrosis
● How does DNA damage and p53 cause cell injury? DNA damage triggers
accumulation of p53: which can arrest the cell or lead to apoptosis.
arrests cell cycle at G1 → repair.
if damage severe → apoptosis
If p53 mutated → damaged cells survive → cancer transformation
