Cell Injury & Necrosis Flashcards
What is Pathology?
Pathology is the study of disease, which can have either a cellular or a tissue basis. The symptoms and signs of a disease are caused by changes in the structure and function of cells and tissues.
A pathological disease description requires…?
- definition
- clinical presentation
- aetiology (cause of disease)
- pathogenesis (mechanisms of cell and tissue injury)
- morphology (structure which can be macroscopic or histologic)
What are the two type of cell injury?
- Necrosis
2. Apoptosis
Explain the Pathological process of Necrosis?
Definition: accidental cell death. There are different structual patterns, but the essential cellular processes are similar in all types.
Aetiology: There are many causes: -Hypoxia/anoxia: lack of oxygen impairing cellular metaboloism (↓ ATP generation from oxidative phosphorylation in mitochondria) - Microbial infection -Drug/toxin induced injury -Physical trauma: burns, radiation
Clinincal Presentation: necrosis induces an inflammatory reaction and can compromise organ function especially in the context of ischaemia and infarction.
Pathogenesis: Not all cell injury leads to necrosis; up to a certain point, injury can be reversible however as the mitochondrial production of ATP becomes more and more depleted, the likelihood of reversal decreases.
Morphology: The ‘naked eye’ appearance is important in pathology. For necrosis, infarctions are often very well demarcated in terms of tissue damage. In solid organs, necrosis looks yellow in colour and it is reffered to as coagulative necrosis.
Histological morphology is also crucially important. dissolution of the nucleus is an important change in necrosis. The nuclear changes from breakdown of DNA and proteins can either show nuclear shrinkage (Pyknosis) or nuclear fragmentation (karyorrhexis) or complete dissolution of the nucleus giving just a ‘ghost cell’ outline in histological images. Furthermore, the tissue becomes more eosinophilic which means that they will stain more pink in a H&E stain.
What is Infarction?
death of tissue due to loss of blood supply, most often as a result of arterial occlusion.
Evidence of infarction may not be present until some time after the cell death.
What is Ischaemia?
most common cause of cell injury in clinical medicine. It can be caused by a reduced blood flow due to mechanical arterial obstruction. It is very dangerous as it can lead to death of cells in 20-30 minutes.
Example: Ischaemic heart disease: AMI
Explain Liquefactive necrosis?
The brain typically undergoes liquefactive necrosis during cerebral infarctions or stroke. This type of necrosis is characterised by digestion of dead cells resulting in transformation of the tissue into a viscous liquid mass or cavity.
Explain Caseous Necrosis?
Caseous necrosis is seen almost characteristically in the lung as a consequence of necrotising granulomatous inflammation due to tuberculosis giving a ‘cheese-like’ appearance. It has no distinct borders and occurs when tissue dissolution by enzymes is more advances than in coagulative necrosis but not enough to liquefy the tissue.
Explain some Mechanisms of cell injury involving mitochondrial damage?
Mitochondrial damage is the central event during cell injury as it causes a failure in energy production.
This causes calcium to move into the cells without regulation. Usually Ca influx in heavily regulated because it is dangerous in large levels in the cells.
This leads to membrane damage and cell death.
Mitochondrial Damage can: - decrease ATP - Increase ROS >> -Influx of calcium >> -membrane damage >> - Protein misfolding and damage
What is Reperfusion Injury?
If the oxygen is reperfused to the hypoxic area too quickly the reactive oxygen species can be produced which can damage proteins, membranes and cause mutations.
Explain the Pathological process of Apoptosis?
Definition: regulated cell death that eliminates unwanted and unrepairable cells with minimal host inflammatory response. There are two pathways of apoptosis: the intrinsic (mitochondrial pathway) and extrinsic (death receptor pathway). It occurs in response to both physiological and pathological stimuli.
Features: Energy dependent process in which the cell membranes remain intact and functional. It involves single cells or small groups of cells rather than large areas of tissue as seen in an infarct.
Pathological Aetiology: Apoptosis is caused by: - DNA damage - Accumulation of misfolded proteins - Viral infections - Immunological reactions
Morphology: cell shrinkage, condesation of nuclear chromatin as well as the formation of cytoplasmic ‘blebs’ and then apoptotic bodies (which are membrane bound structures packed with cell organelles and possible nuclear fragments); phagocytosis of apoptotic bodies by macrophages.
