MOD - Cell Injury Flashcards
What is ischaemia?
What are the effects?
Loss of blood supply to due to reduced arterial supply or reduced venous drainage.
Reduced supply of oxygen and nutrients, resultant injury more rapid and severe than hypoxia
What is a common form of cell death? And explain?
Hypoxia - oxygen deprivation, decreased aerobic respiration.
Length of time a cell can tolerate hypoxia varies, some neurones can only tolerate for a few minutes, dermal fibroblasts can tolerate for a number of hours.
What are the causes of hypoxia? (4)
Hypoxaemic - arterial content of oxygen is low
Anemic - decreased ability for Haemoglobin to carry oxygen
Ischaemia - interruption to blood supply
Histiocytic - inability to use oxygen in cells due to disabled oxidative phosphorylation enzymes
Name the other causes of cell death and describe (6)
Physical agents - Trauma, temperature extreme, electrical currents
Chemical agents and drugs - high O2 concentration, positions, insecticides, alcohol, asbestos
Microorganisms - viruses, bacteria, fungi
Immune mechanisms - hypersensitivity reactions (urticaria) and autoimmune (Graves’ disease)
Dietary insufficiency and deficiencies
Genetic abnormalities - inborn error of metabolism
What are the four components of a cell that are principal targets of cell injury?
Cell membranes- role in homeostasis
Nucleus - genetic material of the cell
Proteins - structural proteins forming cytoskeleton and enzymes involved in metabolic processes of cell
Mitcochondria - oxidative phosphorylation and production of ATP
In what ways does reversible hypoxia affect the cell? And why? (3)
Cell swelling - Cell is deprived of oxygen, so produces less ATP
Loss of activity to Na+/K+ pump. Na+ conc rises = cell swells
Reduced cell pH - accumulation of lactic acid from anaerobic respiration
Disruption of protein synthesis - ribosomes detach from ER, can cause intracellular accumulation of substances e.g. fat and denatured proteins
What ways does irreversible hypoxia effect the cell?
Increased membrane permeability
Massive influx of Ca2+ ions Into cytoplasm
Calcium ions are biologically very active and high concentrations result in the activation of an array of potent enzymes such as ATPases, phospholipases, proteases and endonucleases.
What test can be undertaken to check for irreversible cell damage, and why?
Blood test - types of substance found indicates where cell damage is
When cell membranes are irreversibly damaged intracellular substances leak about into circulation and can be found in the blood
What is Ischaemia reperfusion injury?
Blood flow returning to a tissue that has been subjected to Ischaemia and sometimes the tissue injury is worse than if blood was not restored.
What may cause Ischaemia reperfusion injury?
Increased production of oxygen free radicals
Increased number of neutrophils
Delivery of complement proteins and activation of complement pathway
How does cyanide toxicity work on a cell?
Chemical combine with cyanide which binds to mitochondrial cytochrome oxidase and blocks oxidative phosphorylation
Why do free radicals cause cell damage?
They have a single unpaired electron, giving them an unstable configuration and so they react with other molecules producing further free radicals.
What do free radicals damage?
Lipids in cell membranes
Proteins, carbohydrates and nucleic acids
Known to be mutagenic
Why are free radicals essential? (2)
Kill bacteria.
Cell signalling
Produced by leucocytes
What are the three free radicals of particular biological importance?
OH (hydroxyl) most dangerous
O2- (superoxide)
H2O2 (hydrogen peroxide)
How is the OH free radical produced?
Radiation can directly lyse H20
Fenton and Haber-Weiss reactions produce OH. Fenton reaction important in injury where bleeding occurs as when blood is around iron is available for production of free radicals
What is the bodies defence against free radicals?
Anti-oxidant system which consists of
Enzymes - superoxidse dismutase (SOD) and Catalase
Free radical scavengers - neutralise free radicals e.g. Vitamin A,C,E
Storage proteins - sequester transition metals in the ECM
By what mechanism do cell utilise heat shock proteins (HSP)
What happens to the HSP?
Down regulate usual protein synthesis and up regulate heat protein synthesis.
They stay in the cell where they are concerned with protein repair
How do heat shock proteins work?
Recognise proteins that are incorrectly folded and repair them by ensuring they are folded correctly.
If they cannot repair them, they destroy them
Why are heat shock proteins important in cell injury?
Name a heat shock protein.
Heat shock response plays a key role in maintaining protein viability and maximising cell survival.
Ubiquitin
What is the best method to diagnose cell death?
Dye exclusion technique - dye put into the cell medium, if it doesn’t take it up = cell is alive
What are the three main alterations to cells that can be seen with injury in light microscope?
Cytoplasmic changes - reduced pink staining due to accumulation of water. Increased pink staining due to detachment of ribosomes from ER and accumulation of proteins
Nuclear changes - chromatin subtly clumped (reversible)
Abnormal intracellular accumulations
Name 4 reversible cell injury changes that can be seen under an electron microscope
Swelling - cell and organelles
Cytoplasmic blebs - symptomatic of cell swelling
Clumped chromatin - due to reduced pH
Ribosome separation from ER - due to failure of energy dependent processes of maintain ribosomes in right location
Name 4 irreversible changes that can be seen under an electron microscope in cell injury
Increased cell swelling
Nuclear changes - pyknosis, karyolysis or karyorrhexis
Swelling and rupture of lysosomes - reflects membrane damage
Membrane defects
Appearance of myelin figures
Lysis of ER due to membrane defects
Define oncosis
Cell death with swelling, the spectrum of changes that occur prior to death in cells injured by hypoxia and some other agents
Define apoptosis
Cell death with shrinkage.
Cell death induced by down regulated intracellular program where a cell activates enzymes that degrade its own nuclear DNA and proteins.
Define necrosis
In a living organism the morphological changes that occur after a cell has been dead some time e.g. 4-24hours.
The changes in appearance are largely due to the progressive degradative action of enzymes on lethally injured cell.
NOT a type of cell death, describes morphological changes.
Name the four types of necrosis.
Necrosis is seen with damage to cell membrane, cell contents leak out of the cell and inflammation is often seen.
Coagulative
Liquefactive
Caseous
Fat necrosis
Describe coagulative necrosis
Denature of proteins dominates over release of active proteases, meaning that dead tissue has a solid consistency.
Cells proteins uncoil and become less soluble
‘Ghost Outline’ outline of cells
After a few days, dead tissue incites an inflammatory reaction with consequent infiltration by phagocytes.
Describe liquifactive necrosis
Active enzyme degradation greater than denaturation and this leads to enzymatic digestion of tissues.
(Proteins undergo dissolution by cells own enzymes)
It is seen in massive neutrophil infiltration because neutrophils release proteases and therefore bacterial infections.
Seen in the brain - fragile tissue without support from robust collage nous matrix
Tissue becomes a viscous mass and if there is acute inflammation pus is present.
Describe caseous and fat necrosis.
Note - These special types of necrosis only occur under limited set of circumstances.
Caseous - cheesy appearance with naked eye. Characterised by amorphous debris (NOT ghost outline). Particularly associated with infections e.g. TB.
Fat - destruction of adipose tissue typically as consequence of acute pancreatitis, during inflammation of pancreas realise of lipases which act on pancreas and fat in abdo cavity - causes release of free fatty acids which can react with calcium to form chalky deposits. Can be seen on Xrays and with naked eye - candle wax appearance.
Can occur after direct trauma e.g. Breast tissue. Heals leaving an irregular scar that can mimic a nodule of breast cancer
What is a clinical term to describe necrosis visible to the naked eye?
Describe the three types.
Gangrene - can be wet or dry depending on whether necrosis is modified by exposure to air resulting in drying (dry or by infection with mixed bacteria (wet).
Dry gangrene - dry crisp appearance of umbilical cord, gangrenous toes
Gas gangrene - (wet gangrene) that has become infected with anaerobic bacteria that produces visible and palpable bubbles of gas within the tissue.