2. Causes and Mechanisms of Cell Injury and Cell Death Flashcards
What are three different types of disease?
Genetic
Acquired
Multifactorial
What is the aetiology of genetic disease?
Chromosomal disorders- abnormal numbers and abnormal structures
Prenatally acquired gene disorders - single gene disorders
What are the features associated with downs syndrome?
Increased incidence with increasing maternal age Congenital Heart Disease Predesposition to Leukaemia Early Alzheimer's Disease Learning Disability
What is CF?
Single gene mutation on chromosone 7
A disorder of ion transport in epithelial cells
What are features of CF?
Alteration in the mucus produced at epithelial surfaces
Thick mucus plugs ducts and tubules of glands
High sweat sodium and chloride concentration
Chronic Lung Disease
Pancreatic insufficiency
Malnutrition
Male Infertility
What is significant about autosomal dominant inherited single gene disorder?
the defective product of the gene is usually a structural protein, not an enzyme. Structural proteins are usually defective when one of the allelic products is nonfunctional;
What is significant about enzymes of autosomal recessive inherited single gene disorders?
enzymes usually require both allelic products to be nonfunctional to produce a mutant phenotype:
What is the aetiology of acquired disease?
Infections
Enviromental- chemical + physical
Nutritional
What is a deficiency of vitamin C?
Scurvy
What is a deficiency of vitamin D?
Rickets
What is the aetiology of multifactorial disease?
A combination of genetic factors and environmental factors
When does cell injury occur?
Occurs when cells are stressed so severely they are no longer able to adapt
What are the two types of cell injury?
Reversible (non-lethal) and irreversible (death)
What is the cellular response to stress?
Stress leads to an cell adaptation and if there is an inability to adapt this will lead to a cell injury
What is the cellular response to severe cell injury?
Causes an irreversible injury which will lead to either necrosis or apoptosis
What is the cellular response to mild cell injury?
Reversible injury where the normal cell will resume through homeostasis
Stress will lead to an adaption
An injury stimulus will cause another cell injury
What happens in the cell during injury?
Mechanical Disruption of cells Insufficient energy Blockage of metabolic pathways Failure of membrane pumps Generation of free radicals Damage to DNA Release of lysosomal contents
What does damage to ATP lead to?
Loss of energy dependent cellular fucntions
What does cell membrane damage lead to?
Mitochondrial failure -ATP
Lysosomes -required for enzymatic digestion of cellular components
Plasma membrane- loss of cellular contents
Why is ATP depletion important?
tissues with low glycolytic activity eg neurons, cardiac muscle where ATP depletion is dependent on oxidative phosphorylation
What causes early release of calcium into the cytosol?
Ischaemia and some toxins
Cytosolic free calcium levels are 10 fold lower than extracellular fluid and maintained by ATP dependent pumps
What can lead to oxidative stress?
Reactive oxygen species (free radicals) accumulate when production exceeds the cells antioxidant defences
What is the significance of the loss of the plasma membrane?
Maintain ionic balance between compartments occurs as a primary or secondary consequence of virtually all types of cell injury and particularly affects the mitochondria
What are examples of reversible cell injury?
Reduced oxidative phosphorylation resulting in depletion of ATP energy stores
Cellular swelling caused by changes in ion concentrations and water influx.
What two morphological examples of reversible cell injury?
Swelling of the cell (Hydropic change ) Fatty change (steatosis)
What is hyopic change?
Impaired function of energy- dependent ion pumps in plasma membrane
What is steatosis?
Deranged lipoprotein transport leads to accumulation of lipid in the cytoplasm of heptocytes
What are causes of steatosis?
Alcohol and obesity
Define necrosis?
Catastrophic cell death following injury accompanied by the release of potent mediators of inflammation
Define apoptosis
A defined orderly sequence of intracellular events leading to cell death
What are factors that cause necrosis?
Decreased oxygen
Infection
Toxins
Trauma
What are the distinct patterns of necrosis?
Colliquative
Coagulative
Caseous
What is the most commonest form of necrosis? and how is this viewed upon microscopy?
Coagulative
Peservation of the basic outline of the cells is seen until cells removed by phagocytosis
Where is colliquative necrosis found?
Seen only brain
What is caseous necrosis?
Cheese like
Dead tissue show no structure cell outlines not evident on microscopy
What are features of apoptosis?
Energy dependent:active process
Cells break into fragments apoptotic bodies and express vitronectin
No inflammatory reaction
What are caspases?
Intracellular proteases which play an important role
What activates caspases?
Extrinsic pathway -signals from outside the cell
Intrinsic pathway-internal pathways such as DNA damage
Why do we need apoptosis physiologically?
Eliminates cells no longer needed maintaining a steady number of various cell populations
Why do we need apoptosis pathologically?
Eliminates cells that are injured beyond repair
What are the stages of apoptosis?
Cell shrinkage Chromatin condensation Membrane Blebbing Nuclear Collapse Continued Blebbing Apoptotic Body formation Lysis of apoptotic bodies
Learn differences between apoptosis and necrosis
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