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
what is the outcome of incomplete repair after injury and damage?
repair scarring
what is the outcome of cell injury affected by?
The type of cell affected:
- Adaptive capability of cell affected
- Pre-existing disease
The damaging agent:
- Duration / Severity of exposure
- Damage that affects structures required for healing eg blood vessels with radiation
Other host factors
what are the classifications of cell types?
Labile : GI Tract, Bone Marrow Stable: Hepatocytes, Endothelium Permanent: Neurones, Skeletal Muscle
what are cells that are lost replaced by?
a pool known as stem cells
where are stem cells located?
in discrete compartments
what does the integrity of stem cell compartment determine?
the regenerative capacity of the tissue
what is stem cells vulnerable to?
radiation:
- impair regenerative capacity
- transmit mutations to daughter cells
Describe complete repair.
Labile and stable cell populations :
- Proliferate to replace lost cells
- Cessation with contact inhibition
Death of permanent cell populations – return to normal is not possible.
Tissue architecture must be preserved
Examples: Hepatitis A
what does repair with scarring follow?
injury with damage to tissue architecture
what does repair with scarring require?
formation of granulation tissue
How does repair with scarring proceed through?
organisation to fibrosis ( scarring)
-fibrous scar contracts by up to 80%
what is an important precursor to repair damaged tissue?
granulation tissue
Describe formation of granulation tissue?
- Capillary endothelial cells proliferate, grow into the damaged area and form fragile vascular channels
- Admixed with other cells: neutrophils, macrophages and fibroblasts and myofibroblasts
- Collagen deposition is associated with scar formation that gradually matures and contracts (by up to 80%)
What is first intention repair with scarring?
Surgical scar
- closely apposed edges
- minimal granulation tissue
- minimal fibrosis
What is second intention repair with scarring?
Ulcerated surface
- Edges widely separated
- prominent granulation tissue
- prominent fibrosis
what is wound contraction caused by?
action of myofibroblasts
what does wound contraction minimise?
volume of wound
what is wound contraction a value of?
wound contraction
when can wound contraction cause problems?
- Stenosis or stricture eg GI tract, CBD
- Contracture may also cause cosmetic damage and impair mobility
what local factors influence wound healing?
- Type of cell / tissue
- Type of injury (comminution, compound)
- Foreign material (exogenous, interposed soft tissues)
- Infection
- Blood supply
- Nerve supply
- Local disease eg neoplasia
- Stability
what systemic factors influence wound healing?
-Age
-General health: Nutrition ( General diet, Vitamin C) Specific diseases (Diabetes mellitus, Immunodeficiency) Drugs(Steroids, Cytotoxic drugs )
Excessive scar formation.
- Hypertrophic scar
- Keloid
