Flashcards in Session 1 - Cell injury and Death Deck (75):
Give five causes of cell death
a consequence of failed homeostasis with subsequent morphological and / or functional disturbances
What three factors determine the degree of damage to a cell?
- Type of cell
- Severity of injury
- Type of injury
What happens in some cells if damage is minor?
What happens if it severe?
What is hypoxia?
Body or some tissue within the body is deprived of oxygen
What are three mechanisms by which hypoxia can occur
What is ischaemia?
Interrupted blood supply due to blockage or laceration.
Decrease in oxygen AND substrate
More rapid and severe injury than hypoxia
What is hypoxaemia?
Inadequate O2 getting into blood
Give three factors which may cause hypoxaemia
* Reduced inspired O2 e.g. at the top of a mountain
* Normal inspiration but absorption into the blood is impaired by lung disease
* Reduced carrying capacity of O2 e.g. due to anaemia
What is histocytic hypoxia?
What is Anaemic hypoxia?
Inability of the cells to use O2 due to disable oxidative phosphorylation enzymes e.g. due to cyanide poisoning.
Decreased ability of haemoglobin to carry oxygen (anaemia, CO poisioning)
What are the four main chemical types which cause damage to cells?
Over the counter drugs and prescription drugs
How can paracetamol damage cells?
If overdosed, depletes glutathione, an anti oxidant and NAPQI (Phase one metabolite) causes damage to hepatocytes, causing liver damage
What cells does alcohol affect in particular?
How do cigarettes damage cells?
* Particulates cause physical damage to epithelium
* Chemical carcinogen
Where is the impact of infection greatest in society?
Areas of poverty
What are four types of infectious organisms?
How can Helmiths cause damage?
Fillriasis - worms block lymphatic vessels
How can eukaryotes cause damage?
protozoa and fungi e.g. thrush – candida causes a superficial mucosal fungal infection
Give a disease caused by bacteria
Syphilis, among many, many others
Give a disease caused by a virus
HIV, or whatever you just thought in your head
How can cells be damaged physically?
Extremes of temperature
Give two ways cells can be damaged by the immune system, and provide examples
1. Hypersensitivity reactions: Host cells damaged in overlyreactive immune response
e.g. uticaria (hives) causes inflammation in the skin
2. Autoimmune reactions: immune system fails to distinguish self from non-self
e.g. Grave’s disease > hyperthyroidism
What are the two nutritional discrepancy's that can cause damage?
Give an example of a nutritional defiency causing cell damage
vitamin C > scurvy
Give an example of a nutritional excess causing cell damage
Lipids --> atherosclerosis
What is necrosis?
a spectrum of morphological changes that occur after cell death in living tissue
What is apotosis?
programmed, single cell death
What type or reaction is apotosis?
* Energy requiring process
When can apotosis occur?
* May be physiological e.g. aging cell destruction or pathological
What is a lethal damage stimulus?
One that cannot be recovered or adapted from, which will result in apotosis or necrosis
What determines whether a cell undergoes necrosis or apotosis?
the magnitude and type of injurious stimulus
When does a cell undergo necrosis?
After severe damage
When does a cell undergo apotosis?
lower-grade damage or immune-mediated damage
What is a key physiological determinant in how a cell dies?
how much cellular ATP is present
What if there is little ATP in a dying cell?
It will undergo necrosis
What are the primary targets for damaging stimulus?
cell membranes, mitochondria, cytoskeleton, and cellular DNA
Give four results of a depletion of cellular ATP
Failure of Na/K/ATPase pump
Failure of membrane calcium pumps (NCX)
Switch to Anaerobic Respiration
Failure of protein synthesis
What is the sequence of events leading to decreased ATP?
No O2 for oxidative phosphorylation, due to hypoxia or ischaemia
What are the four types of necrosis? Give two main and two special
* COAGULATIVE and LIQUEFACTIVE (main types)
* CASEOUS and FAT NECROSIS (special types)
What happens in coagulative necrosis?
* Protein denaturation causes proteins to clump together leading to solidity
*Tissue architecture is preserved
*commonly follows ischaemia
What is liquefactive necrosis?
* Release of active enzymes, especially proteases, by neutrophils
*causes dead tissue liquefication
* When cell death is associated with large numbers of neutrophils they release proteolytic enzymes
* Seen in brain because it is fragile
What is caseous necrosis?
Tissue appears amorphous
Associated with infection such as TB
What is fat necrosis?
* Occurs when fat cells die, most commonly as a result of pancreatitis (release of lipases) or trauma to fatty tissue
What is a significant feature of fat necrosis
* Importance: calcium deposits can occur in the dead tissue which is visible on x-ray and in surgery as chalky deposits. Calcium reacts with fatty acids.
What is gangrene?
Necrosis visible to the naked eye
What are two types of gangrene, and what can it be the result of?
Coagulative or liquefactive, often result of ischaemia
Why is liquefactive gangrene dangerous?
Individual becomes predisposed to septicaemia
What is an infarction?
2. Infarction: a CAUSE not type of necrosis. Can be coagulative (heart) or liquefactive (brain).
What do umbilical cords undergo?
What are two types of infraction?
White or red
What is white infarction?
* White: occurs with the occlusion of an “end” artery (sole source of arterial blood to a segment of an organ). If occluded, the tissue will die and appear white (due to lack of blood).
What is a red infarction?
* Red: extensive hemorrhage in dead tissue. Dual blood supply is one cause, infarct in main arterial blood supply but not in second. Insufficient resources from second blood supply, so tissues die surrounded by blood.
What is an intrinsic trigger of cell apotosis?
DNA damage > P53 induced apotosis
What is the mechanism of intrinsic cell apotosis?
o Mechanism: DNA damage causes increased mitochondrial permeability. Cytochrome C is released from mitochondria and interacts with APAF1 and capase 9 to form an apopotosome that activates various downstream capases (enzymes that mediate cellular affects of apotosis)
What are the three stages of apotosis?
Initiation, execution and degradation + phagocytosis
What is an extrinsic trigger of apotosis?
Death signals released and bind to death receptors, leading to capase activation independent of mitochondria
Give two types of death signals
TRAIL and FAS LIGAND
Give a type of death receptor
TRAIL - R
Which is Bcl-2?
* Bcl-2: prevents cytochrome C release from mitchondria and inhibits apoptosis
What are capases?
effector molecules of apotosis
What is P53?
Guardian of the genome, mediates apotosis in response to cell damage
Give some cytoplasmic microscopic changes in necrosis
Cytoplasmic: reduced pink staining due to water accumulation followed by increased staining due to detachment and loss of ribosomes and accumulation of denatured proteins.
Give some nuclear microscopic changes in necrosis
Nucleus: clumped chromatin followed by various combinations of pyknosis (small nucleus), karryohexis (fragmented) and karryolysis (absent nucleus)
Give five reversible signs of cell necrosis visible via electron microscope
* Swelling of cytoplasm and organelles due to Na+/K+ failure
* Clumped chromatin due to reduced pH
* Autophagosomes due to catabolic response from low available energy
* Ribosomes dispersion due to failure of energy dependent process of maintaining ribsomes
* Cytoplasmic blebs
Give five irreversible signs of cell necrosis visible via electron microscope
* Nuclear changes > pyknosis etc
* Lysosome rupture > reflects membrane damage
* Membrane defects
* Myeline figure due to membrane defects
* Lysis of endoplasmic reticulum due to membrane defects
What is the first step of pathogenesis of hypoxia?
1. No O2 for oxidative phosphorylation > loss of ATP > ß Na+/K+ pump > cell swelling as water doesn’t leave
What is the result of lack of oxygen on mechanism of ATP production in a cell suffering from hypoxia?
2. Anaerobic metabolism > Ý lactic acid/phosphates > ß pH > chromatin clumping
What is the result of decreased protein synthesis in a cell suffering from hypoxia?
3. ßProtein synthesis > altered metabolism > intercellular accumulations e.g. fat and denatured protein
What is the irreversible point at which cell will die?
When there is massive increase in intracellular calcium
What does calcium do in a cell?
Causing mortal injury
What do free radicals do to cells?
* Damage lipids, proteins (fragmentation and oxidation) and nucleic acids (mutagenic affect)
What are the useful roles of free radicals?
Bacterial destruction and cell signalling
What does heat shock do to a cell?
Increased transcription and translation of heat shock proteins
The repair damaged proteins and correct folding
Important as maintaining protein viability maximizes cell survival
Give 5 microscopic changes of apotosis?
- Single cells or small clusters affected
- Intensely eosinophillic and dense nuclear fragments
- Cell shrinkage
- Nuclear fragmentation
- Chromatin condensation