Cell Injury and Death Flashcards
List 4 factors which contribute to the maintenance of a cellular steady state
- Preservation of genetic integrity 2. Normal enzyme content 3. Intact membranes and transmembrane proteins Adequate supply of substrates and oxygen
Define ‘Cell Injury’
A biochemical and/or morphological change which occurs when the steady state is perturbed by adverse influences
What do each of these prefixes or suffixes mean? Ana- Dys- Hyper- Hypo-
Ana- = ‘without’ Dys- = ‘disordered’ Hyper- = ‘extreme or beyond normal’ Hypo - = ‘Below normal’
What do each of these prefixes or suffixes mean? Meta- -itis -oma -osis
Meta- = ‘change’ -itis = ‘inflamed’ -oma = ‘tumour’ -osis = ‘ condition, disease or increase’
What do these suffixes mean? -oid -penia -cytosis -ectasis -plasia -opathy
-oid = ‘resemblance’ -penia = ‘deficiency’ -cytosis = ‘increase in cell number’ -ectasis = ‘dilatation’ -plasia = ‘formation’ -opathy = ‘denoting disease or disorder’ (governed by the prefix i.e. ‘neuropathy’ - a disease of the peripheral nerves
List 4 common causes of cell injury
Oxygen availability Physical Trauma Chemical Agents Infectious organisms Irradiation Immunological Genetics Ageing
What is the difference between hypoxia and anoxia and what is the common cause of both?
Hypoxia is a reduction in the availability of oxygen Anoxia is the complete loss of oxygen delivered to cells Common cause is ischaemia
What is the danger with radical re-oxygenation of tissues?
Reperfusing tissues can generate oxygen free radicals and further cause damage
Explain the mechanism of cyanide poisoning
Primary effect of cyanide poisoning is impairment of oxidative phosphorylation. This is catalysed by the cytochrome oxidase enzyme system in the mitochondria, and the impairment arises from the inhibition by cyanide of cytochrome oxidase
What are the consequences of mechanical trauma?
Disruption of cell structure Thrombosis leading to ischaemia
Which product is toxic in the breakdown of paracetamol?
NAPQI N-Acetyl-P-Benzo-Quinone Imine
What is the treatment for paracetamol poisoning?
Administer activated charcoal (AC) if the patient is alert and presents, ideally, within 1 hour post ingestion. The IV formulation of NAC (Acetate) is commonly used in many institutions for the treatment of acetaminophen ingestion in more severe cases
What are the two secretions from bacteria which are toxic?
Endo- and Exo- toxins
Briefly describe the mechanism of ionisation to the tissue
Generation of free radicals causing direct damage to macro molecules following exposure to a source such as UV light
Give 3 examples of tissues which have a high sensitivity to ionising radiation
Bone marrow Gonads Intestines
Give 3 examples of tissues which have a low sensitivity to ionising radiation
Uterus Pancreas Adrenal
What makes certain cells more sensitive to ionising radiation than others?
The most sensitive cells are those that are undifferentiated, well nourished, dividing quickly and highly active metabolically.
List the targets of cell injury
Mitochondrial function Membrane integrity and function Protein synthesis Cytoskeleton Genetic apparatus
Describe this flow chart
Diminished oxidative phosphorylation and reduced ATP levels
- Activity of plasma membrane ATP-driven “sodium pump” is reduced, with consequent influx of sodium and calcium, leading to isosmotic gain of water and acute cellular swelling
- Anaerobic glycolysis increases to generate ATP from glycogen, which depletes glycogen stores and results in accumulation of lactic acid thus lowering the intracellular pH
- Decreasing pH and ATP levels cause ribosomes to detach from rough endoplasmic reticulum and reduction in protein synthesis
- Note that all these effects are potentially reversible, and the restoration of blood flow eventually allows the cell to recover normal function.
- Cellular swelling or acute cellular oedema is usually associated with hypoxia, but may also occur with fever or damage due to toxins
What is the treatment for free radical toxicity?
Detoxification by superoxide dismutase and antioxidants like vitamins A, C and E
Name 3 factors can cause membrane defects?
Bacterial toxins
Viral proteins
Complement
Cytolytic Lymphocytes
Various physical and chemical agents
What can an iincrease in calcium into the cell cause?
Activates a number of enzymes with potential deleterious cellular effects:
ATPases
Phospholipases
Proteases
Endonucleases
What is the function of an ATPase enzyme?
ATPases transport a variety of different compounds, like ions and phospholipids, across a membrane using ATP hydrolysis for energy. An increased activation of ATPase would hesten ATP depletion
What is the function of a phospholipase enzyme?
Hydrolyses phospholipds into fatty acids. Increased activation of these enzymes will lead to membrane damage
What is the function of a protease enzyme?
Breaks down proteins into amino acids. Increased amounts of proteases will break down membrane and cytoskeletal proteins
What is the function of an endonuclease?
Recognize and ‘cut’ at specific points in DNA
When does cell death occur?
When cells are unable to achieve a new steady state following environmental insults
What is the general reason for cell death?
Due to irreversible breakdown of energy dependant organised interactions between DNA, membranes and enzymes
What are the two types of cell death and what is the key difference between the two?
Necrosis and Apoptosis
Key difference: Apoptosis is active and programmed. Necrosis is passive and unprogrammed
Which type of necrosis is the most common?
Coagulative Necrosis
Name the 4 main types of necrosis
Coagulative
Caseous
Colliquative
Gangrene
What is coagulative necrosis and what are its characteristics?
Denaturation of intracytoplasmic protein
The dead tissue becomes firm and swollen
Tissue shows retention of microscopic architecture
Typical of ischaemic injury (except in the brain)
Cellular proteins may leak into the blood
What is colliquartive necrosis and what are its characteristics?
Necrosis of brain tissue
Total liquefaction and the site is eventually marked by a cyst
The brain unergoes this type of liquefaction because it does not have a collagenous framework
What is caseous necrosis and what are its characteristics?
Form of cell death in which the tissue maintains a cheese-like appearance
Characteristic of TB
Cheese like
Cellular detail in the area of necrosis is destroyed and surrounded by granulamtous inflammation
What is gangrenous necrosis and what are its characteristics?
A type of necrosis caused by a critically insufficient blood supply
Can be dry, wet, gaseous or other
Name 3 physiological examples of apoptosis
Embryogenesis
Involution
Elimination of self reacting lymphocytes
Give 3 examples of pathological apoptosis
DNA/Protein damage
Viral infections
Cell killing by cyto T cells
What does this diagram represent?
The mechanisms of Apoptosis
Which factors required for Apoptosis are sequestered in the mitochondria and what do these molecules activate when released into the
Apoptosis Initiating Factor (AIF) and CytoC
Activate caspases in the cytosol
What are the effector molecules of apoptosis and what are they activated by?
Caspases
Activated by the presence of CytoC and AIF in the cytosol
What is the colloqueal name for P53?
‘The Gaurdian of the Genome’
What is P53 activated by and what does it cause upon activation?
DNA damage
Causes the elimation of damaged cells by apoptosis
When are mutations of P53 very common?
In malignant tumours
How does BCL2 inhibit apoptosis
Sequesters CytoC
Which of necrosis or apoptosis is physiologic and which is pathologic?
Necrosis = Patho
Apoptosis = Physio
Is the plasma membrane intact or disrupted during apoptosis?
Intact in apoptosis
Disrupted in necrosis
What is the staging of the nucleus in apoptosis?
Fragmentation to Apoptotic Bodies
What is the staging of the nucleus in Necrosis?
Pyknosis to Karyorrhexis to Karyolysis
Does necrosus feature adjacent inflammation?
Yes, frequently
It is not present in apoptosis
What is the state of the cell size in necrosis and apoptosis?
Enlarged in necrosis
Reduced in apoptosis
