MoD 1 (Cell Injury) Flashcards
Define hypoxia:
Oxygen deficiency
What are the 4 possible causes of hypoxia?
1) Ischaemia
2) Anaemia
3) Hypoxaemia
4) Histiotoxic
Define Ischaemic Hypoxia:
Oxygen deficiency due to lack of blood
Define Anaemic Hypoxia:
Oxygen deficiency due to lack of or defective haemoglobin
Define Hypoxaemic Hypoxia:
Oxygen deficiency due to lack of available oxygen
Define Histiotoxic Hypoxia:
Oxygen deficiency due to disabled oxidative phosphorylation enzymes
Myocardial Infarction is an example of which type of hypoxia?
Ischaemic hypoxia
CO poisoning is an example of which type of hypoxia?
Anaemic hypoxia
High altitude may cause which type of hypoxia?
Hypoxaemic hypoxia
Cyanide poisoning is an example of which type of hypoxia?
Histiotoxic
What are the 7 main classes of causes of cell death?
1) Hypoxia
2) Physical agents
3) Chemical agents
4) Micro-organisms
5) Genetic
6) Dietary
7) Immune mechanisms
When intracellular ATP drops to ~5/10% of normal levels, which kind of hypoxic injury is caused?
Reversible hypoxic injury
When intracellular ATP drops to ~5/10% of normal levels, why is reversible hypoxic injury caused?
- Na+/K+ ATPase pump fails = increased intracellular Na+ = cell swells
- Increased anaerobic respiration = increased lactic acid = pH drop affects enzyme activity and causes ribosomes to detach from rER
What 4 classes of enzymes are activated by Ca2+ influx, which explains its toxicity?
1) ATPases
2) Proteases
3) Phospholipases
4) Endonucleases
Explain Ischaemia-Reperfusion injury:
The reperfusion of blood to an ischaemic tissue may cause more damage than the initial ischaemia, due to:
- Increased free radical production
- Delivery of neutrophils = inflammation
- Delivery of complement = activates complement cascade
Heat shock proteins are unregulated and triggered by what?
Any injury/shock
What is the role of intracellular heat shock proteins?
Stabilise unfolded proteins
Gives cell more time to repair/degrade
What is the role of extracellular heat shock proteins?
Can stimulate professional antigen-presenting cells
How can you test to see whether a cell is alive or not using dye?
If cell is alive - will not take up dye
If cell is dead - will take up dye
What changes can you see via light microscope in a cell undergoing reversible hypoxic injury?
- Reduced pink staining of cytoplasm (increased water uptake)
- Clumping of chromatin (pH drop)
- Abnormal intracellular accumulations
What changes can you see via light microscope in a cell which has undergone irreversible hypoxic injury?
- Increased pink staining of cytoplasm (ribosome detachment)
- Pyknosis/karryohexis/karrylysis of nucleus
- Abnormal intracellular accumulations
Define pyknosis:
Irreversible condensation of DNA = nucleus shrinks
Define karryohexis:
Irreversible fragmentation of DNA = nucleus fragments
Define karyolysis:
Irreversible dissolution of DNA = nucleus fades
What changes can you see via electron microscope in a cell undergoing reversible hypoxic injury?
- Cell swelling (failing Na+/K+ pump)
- Cytoplasmic blebs
- Clumping chromatin (pH drop)
- Ribosome detachment from rER (less ATP)
What changes can you see via electron microscope in a cell which has undergone irreversible hypoxic injury?
- Cell swelling (failed Na+/K+ pump)
- Pyknosis/Karryohexis/Karryolysis of nucleus
- Swelling/ruptured lysosomes
- Myelin figures and membrane defects
- Amorphous densities in swollen mitochondria
What is a ‘Myelin figure’?
Rolled up ‘scroll-like’ lipid bilayer within the cell, resembling a myelin sheath, due to a damaged cell membrane.
Define Oncosis:
Cell death with swelling, and the process of changes that occur in injured cells prior to death.
Name the 2 processes of cell death:
1) Oncosis
2) Apoptosis
Define Apoptosis:
Cell death with shrinkage (membrane integrity preserved), induced by a regulated intracellular program which activates enzymes to degrade the cells own DNA and proteins.
What is the only physiological apoptosis to occur in the body?
Embryo sculpting
What gene is known as the ‘Guardian of the Genome’?
p53
Describe the intrinsic initiation of apoptosis:
- DNA damage activates p53 = increases mitochondrial permeability
- Mitochondria releases cytochrome c into cytoplasm
- Cytochrome c forms apoptosome with APAF1 and caspase 9 = activates caspases
What is the goal of the intrinsic and extrinsic initiations of apoptosis?
To activate caspases
Describe the extrinsic initiation of apoptosis:
- Death ligands interact with cell, and directly activate caspases
Give an example of a death ligand and its receptor which can induce apoptosis:
TRAIL interacts with TRAIL-R
Define caspase:
Protease which cleaves proteins, breaking up the cytoskeleton and can initiate DNA degradation during apoptosis.
What are the 3 stages of apoptosis?
1) Initiation
2) Execution
3) Degradation and phagocytosis
How does Bcl-2 inhibit intrinsically activated apoptosis?
Prevents release of cytochrome-c from mitochondria
What is an ‘apoptotic body’?
Membrane-bound fragments (containing cellular contents) expressing molecules on their surface to induce phagocytosis
Define Necrosis:
The morphological changes in a living organism that occur after a cell has been dead ~ 12-24hrs
Name the 4 types of necrosis:
1) Liquefactive
2) Coagulative
3) Caseous
4) Fat
What is the most common type of necrosis?
Coagulative
Define coagulative necrosis:
Cell changes that occur after cell death in solid tissue with a collagenous support:
- ‘ghost outline’ of cells (protease release)
- increased pink staining
- nucleus karyolysis
- presence of neutrophils
Define liquefactive necrosis:
Cell changes that occur after cell death in tissue without a collagenous support:
- fluid accumulation of dead tissue degraded by proteases
Define caseous necrosis:
Cell changes that occur after cell death due to tuberculosis:
- tissue forms dry amorphous mass resembling cheese
Define fat necrosis:
Cell changes that occur after adipose cell death:
- white chalky deposits of soap (FA’s released due to lipase, complex with Ca2+ to form soaps)
Fat necrosis is closely associated with what?
Pancreatitis (as leads to lipase release)
Fat necrosis closely represents what kind of cancer?
Breast cancer
Name the 2 types of gangrene:
1) Wet
2) Dry
Define dry gangrene:
The changes visible by naked eye caused by coagulative necrosis, modified by exposure to air
Define wet gangrene:
The changes visible by naked eye caused by liquefactive necrosis, modified by infection with bacteria
Define gas gangrene:
Type of wet gangrene, in which anaerobic bacteria produce bubbles of gas within the tissue
Which type of gangrene may cause septicaemia, and why?
Wet gangrene, due to presence of bacteria
The changes to leaves in the autumn is an example of what type of gangrene?
Dry gangrene
Define infarction:
Obstruction of a blood supply to a tissue (via thrombus/embolism/compression/twisting) causing ischaemic necrosis
What are the 2 types of infarction?
1) Red
2) White
Define white infarction:
Anaemic infarct of ‘end’ artery, causing little or no bleeding into the tissue spaces, resulting in coagulative necrosis.
White infarcts are common in which organs?
Heart, Kidneys, Spleen
Define red infarction:
Haemorrhage infarct caused by:
- Dual blood supply to affected tissue
- Many anastomoses present in tissue
- Venous insufficiency (vein occlusion)
Which type of infarction is usually associated with venous occlusions?
Red haemorrhagic infarct
Which type of infarction is usually associated with arterial occlusions?
White anaemic infarct
What type of necrosis can infarction cause?
1) Coagulative
2) Liquefactive
Which 3 main molecules are released from dying striated muscle cells?
1) Potassium
2) Enzymes
3) Myoglobin
Why are small enzymes released from dying cells before larger enzymes?
Size of pores created in the cell membrane is proportional to the extent of the damage.
What is the use of measuring enzymes when assessing cell damage?
Can inform of:
- Organ/cell type involved
- Extent of damage
- Time of damage
What is Rhabdomyolysis?
Severe destruction of striated muscle cells
What is Mallory’s hyaline?
Eosinophilic intracellular accumulations of proteins due to damaged keratin filaments, associated with alcoholic liver disease.
Alpha1-antitrypsin deficiency causes which diseases in later life?
1) Emphysema
2) COPD
What type of exogenous pigment causes pneumoconiosis?
Coal dust
How does coal dust cause pneumoconiosis?
Excessive amount of coal dust in the lungs triggers an immune reaction which results in fibroblasts secreting collagen = scar tissue = emphysema
Name the endogenous pigment which accumulates due to age-related free radical injury and peroxidation?
Lipofuscin
Accumulation of which endogenous pigment is associate which haemolytic anaemia, blood transfusions, bruises, haemochromatosis etc?
Haemosiderin
Accumulation of which endogenous pigment is associated with jaundice?
Bilirubin
What is meant by ‘pathological calcification’?
Abnormal deposition of calcium salts in tissue.
What are the 2 types of pathological calcification?
1) Dystrophic
2) Metastatic
What is the most common type of pathological calcification?
Dystrophic
Where does dystrophic calcification usually occur?
Dying tissue
Atherosclerotic plaques
Damaged/ageing heart valves NEVER IN PULMONARY VALVE
Tuberculous lymph nodes
What causes metastatic calcification?
1) Increased PTH secretion i.e. tumour or renal failure
2) Bone tissue destruction i.e. leukaemia or Pagets disease
What enzyme do germ cells and cancers contain to allow indefinite replication?
Telomerase
Which part of a chromosome is shortened with every replication?
Telomere
