P2- Injury, Healing and Repair Flashcards
Name the causes of cellular / tissue injury.
- Physical - mechanical , thermal ,electric , Barotrauma
- Chemical - drugs , metabolic , hypoxia , nutrition
- Infectious - cytolysis , toxins , immune response
- Immunological -may contribute to other categories
- Genetic -may contribute to other categories
What can. cause cellular injury?
many agents
Describe mechanics by which cell injury manifest , at a cellular level.
Mechanisms by which cell injury is manifest may be very similar for different causal agents
what are the different phases of cellular injury?
- reversible
- irreversible
what is cellular injury recognised by?
- morphological / Structural features
- biochemical features
what does severe damage in cellular injury lead to?
cell death
What are the vulnerable intracellular systems of mechanics of cellular injury?
-Cell Membrane Integrity
-Aerobic Respiration
-Protein Synthesis :
Enzymes
Structural Proteins
-Genomic Integrity
what is closely related in mechanisms of cellular injury?
structural and biochemical aspects
what are types of mechanics of cellular injury?
- deficiency of metabolite (o2)
- impaired metabolism (respiration and syntheis e.g of proteins)
- Membrane damage (structural -physical/chemical, functional- failure of ion pumps , calcium ion homeostasis )
- DNA damage or loss (radiation, drugs, free radicals)
describe disruptions to membrane integrity.
-Mechanical disruption
Physical trauma, osmotic, freezing, complement, cytotoxic proteins in Tc cells
-Functional disruption
Depletion of ATP, alterations to lipids and protein in the cell membranes e.g. cross linking induced by free radicals
-CSM and internal membranes.
Describe impaired metabolism.
Respiration: -Lack of oxygen e.g blood supply, CO -Block mitochondrial respiratory chain e.g. cyanide binding to cytochrome oxidase Protein synthesis; -Ricin blocks translation at ribosome -Decreased ATP will contribute
Describe DNA damage / loss.
-May not be immediately apparent
-Dividing cells particularly affected – or when there is a growth stimulus
-Non-lethal damage may introduce heritable abnormality that can lead to disease in daughter cells e.g. neoplasia
-Free radicals
Highly reactive and chemically unstable species
Describe metabolite deficiency.
Any essential metabolite: Oxygen: -Aerobic metabolism -Anaerobic pathways induce acidosis -Ischaemia and infarction -Reperfusion injury
Glucose
- Some cells have high requirements and sensitive to deficiency.
- Diabetes mellitus - poor utilisation - absolute or relative deficiency of insulin
Hormones
-Lack of trophic hormones leads to target cell atrophy
what does the severity of damage and the effects on the cells and tissues depend on?
- Type, magnitude and duration of injury
- The type of tissue affected
- The proportion / numbers and types of cells affected
- The effect on the connective tissue scaffold
- The effect on other tissues and structures e.g. blood vessels
what are the stages of cellular insult?
- Normal cell
- cellular insult
- adaptive response
- reversible cell injury (loops to adaptive response and normal cell)
- irreversible cell injury
- cell death
what occurs in reversible damage?
- Reduced aerobic respiration
- Increased anaerobic respiration
- Membrane pumps fail
- Cell swelling
- Accumulation of lipids
what is the recognition of cell injury?
Cell swelling (Hydropic change) :
- Cytoplasm pale and swollen
- Accumulation of fluid
- Function of membranes and membrane pumps affected
- Hypoxia and chemical poisons
Fatty change :
-Accumulate lipid droplets
-Uncoupling of lipid and protein metabolism
-Liver commonly affected
-May see many small vacuoles or one large vacuole
(Both of these events are usually reversible )
what is irreversible damage characterised by?
- Severe damage to cell membranes
- Severe damage to mitochondria
- Leakage of enzymes
- Nuclear changes
what happens in irreversible damage?
ATP Depletion
Cell Membrane Damage;
- Progressive Loss of Phospholipids (Increased Degradation, Reduced Synthesis)
- Lipid Breakdown Products
what are the 2 types of cell death?
Apoptosis : pre-programmed (decides itself)
Necrosis : pathological cell death
Describe features of apoptosis.
-Physiological or
Pathological
-Affects scattered cells: Cells shrink , Apoptotic bodies form, No inflammation
Energy dependent:
Stereotyped sequence of events , Biochemical regulation (Inducers /Inhibitors)
Describe features of necrosis.
- Always pathological
- Affects sheets of cells : Cells swell , Dissolution of organelles, Inflammation
- Not energy dependent
- Descriptive terms : Coagulative, Colliquitive Caseous , Fibrinoid
what is involved in apoptosis?
- inhibitors
- inducers
- Molecular mediators and regulators
- increased apoptosis (AIDS)
- decreased apoptosis (Neoplasia)
what is the outcome of complete repair after injury and damage?
Regeneration Restitution
