Week 7 Flashcards
What are the 6 categories of causes of cell damage?
ATP depletion/ Reduced synthesis
Mitochondria damage
Intracellular calcium
Free radical damage
Defective membrane permeability
Protein misfolding
What does hypoxia interfere with?
Aerobic oxidative respiration
What occurs in hypoxic injury?
Reduced ATP generation
Isosmotic water gain and cellular swelling
Increase in anaerobic glycolysis
Ribosomes detach from RER
Polysomes dissociate into monosomes
At what point in hypoxia does it become irreversible?
After cytoskeleton breaks down and there is a loss of ultrastructural features
What is a reperfusion injury?
Exacerbates tissue damage through paradoxical further injury
What is a free radical?
An atom, molecule or ion with one or more unpaired valence electron
What are ROS?
Reactive Oxygen Species: Free radicals by product of O2 metabolism
What can result in high ROS levels?
Membrane damage and promoted mitochondrial transition
What are the 3 methods of mechanical cell injury?
Direct mechanical damage
Freezing
Osmotic imbalance
What occurs during freezing?
Intracellular and cell membranes perforated by ice crystals
What is atrophy?
Shrinkage in the size of a cell by the loss of cell substance
What is hypertrophy?
Increase in the size of cells and consequently an increase in the size of the organ
What is hyperplasia?
Increase in number of cells in an organ or tissue
What is metaplasia?
Reversible change in which one adult cell is replaced by another adult cell type
Describe some differences between apoptosis and necrosis
Cell size swollen in necrosis and shrunken in apoptosis.
Membrane disrupted in necrosis and intact in apoptosis.
Inflammation nearby in necrosis not in apoptosis.
Rarely pathological in apoptosis.
What are the types of necrosis?
Coagulative necrosis
Colliquative necrosis
Caseous necrosis
Gangrenous necrosis
Fat necrosis
What causes coagulative necrosis?
Ischaemia
What occurs in caseous necrosis?
Coagulated tissue no longer resembles the cells but is in chunks of unrecognisable debris
Where is colliquative necrosis normally seen?
Brain
What occurs in colliquative necrosis?
Enzymes in neutrophils dissolve tissues nearby causing accumulation of pus effectively liquefying the tissue
What are the 2 types of gangrenous necrosis?
Wet
Dry
What occurs in fat necrosis?
Enzymes (lipases) release free fatty acids, which with calcium produce soapy deposits in tissues
What is autolysis?
Lysis of tissues by their own enzymes following the death of the organism
What are the 3 classifications of cell regeneration?
Labile
Stable
Permanent
What regeneration capacity do labile cells have?
Good capacity to regenerate
What regeneration capacity do stable cells have?
Divide slowly but can regenerate if needed
What regeneration capacity do permanent cells have?
No means of effective regeneration
What can cause inflammation?
Microbial infections
Hypersensitivity reactions
Physical agents
Chemicals
Tissue necrosis
How does microbial infection cause inflammation?
Bacterial exotoxins
Bacterial endotoxins
Viral intracellular multiplication leading to cell death
May cause hypersensitivity reactions
What are the cardinal signs of acute inflammation?
Rubor
Calor
Tumor
Dolor
Loss of function
What are the 6 stages of inflammation?
Release of chemical mediators
Vasodilation
Increased vascular permeability
Fluid accumulation
Cellular recruitment
Phagocytosis
What is exudation?
The process of increased vascular permeability and net flow of fluid out of vessels in acute inflammation
What cells are found commonly in cellular exudate?
Neutrophils
How do neutrophils move?
Contraction of cytoplasmic microtubules
Chemotaxis in response to inflammatory chemicals
What are the stages of neutrophil migration out the vessel?
Margination
Pavementing
Passage between endothelial cells
Pass through basal lamina and migrate into adventitia
What causes adhesion of neutrophils?
Interaction of paired adhesion molecules
What chemicals are released by the original inflammatory stimulus to up regulate P-selectin and PAF?
Histamine
Thrombin
What is PAF?
Platelet Activating Factor
What does histamine do?
Causes vascular dilation and permeability
What is histamine mainly released by?
Mast cells
What cells release lysosomal compounds?
Neutrophils
What do leukotrienes do?
Have vasoactive properties
What can prostaglandins do?
Some cause increased vascular permeability
Some cause platelet aggregation
What is the effect of serotonin in acute inflammation?
Vasoconstriction
What are chemokines?
Family of chemicals which attract more white blood cells to the site of inflammation
What are the four enzyme cascade systems in plasma?
Coagulation system
Kinins
Fibrinolytic system
Complement system
What do C3a and C5a do in acute inflammation?
Chemotaxis of neutrophils
Histamine release from mast cells
Increased vascular permeability
What does C567 do in acute inflammation?
Chemotaxis of neutrophils
What do C4b, 2a and 3b do in acute inflammation?
Opsonisation of bacteria
What are the benefits of inflammation?
Dilution of toxins
Entry of antibodies
Transport of drugs
Fibrin formation
Delivery of nutrients and oxygen
Stimulation of immune response
What are the 4 possible outcomes of acute inflammation?
Resolution
Suppuration
Scarring or fibrosis
Chronic inflammation
What is suppuration?
Formation of pus, a mix of neutrophils, debris, bacteria etc.
What is primary intention?
2 edges of wound can be brought together, fibrin joins them initially and over time epidermal regrowth and collagen synthesis strengthen the join
What occurs in secondary intention?
Tissue defect filled by granulation tissue, epithelial regrowth over the surface, fibrous scar forms and contracts over time
When can complete healing occur in the liver?
Loss of hepatocytes but no damage to architecture
What type of damage leads to scarring/impaired function in the kidneys?
Destruction of glomerulus or damage to interstitium
What kind of smooth muscle cells regenerate?
Vascular smooth muscle
What kind of neural tissue can regrow?
Peripheral nerves depending on alignment and continuity
What occurs in cellular exudate when inflammation progresses to chronic?
Neutrophils are replaced with lymphocytes, plasma cells, macrophages
Give some examples of primary chronic inflammation?
TB
Leprosy
RA
Chronic inflammatory bowel
Crohn’s
What is the most common type of acute inflammation to progress to chronic?
Suppurative
What can be provoked by presence of foreign material?
Granulomatous inflammation, foreign body giant cells
What are the macroscopic signs of chronic inflammation?
Chronic ulcer
Chronic abscess cavity
Fibrosis/thickening of tissue
How do lymphocytes, plasma cells, macrophages and eosinophils appear microscopically?
Lymphocytes - Small purple dots
Plasma cells - Fried eggs
Macrophages - Large blobs
Eosinophils - Tomatoes with sunglasses
What do lymphocytes do in chronic inflammation?
B - Meet antigens, turn into plasma cells
T - CD8+ cytotoxic function and recruiting other immune cells
CD4+ Activate killer T and plasma cells
What are cytokines?
Small proteins that enhance cell mediated immunity and enhance the antibody response
What is a granuloma?
A collection of histocytes
What is granulomatous inflammation associated with?
Foreign body reactions
Infections (e.g. TB)
Sarcoidosis
Crohn’s
How are giant cells formed?
Macrophages collide, potentially when trying to eat the same particle
What are the 3 giant cell types?
Foreign body type
Langhans
Touton
Does apoptosis or necrosis require energy?
Apoptosis
What are the 2 mechanisms of inducing apoptosis?
Extrinsic
Intrinsic
What receptors initiate the extrinsic pathway of apoptosis?
Death receptors (Fas and TNF)
Where is the intrinsic pathway of apoptosis initiated?
Mitochondria
What is the function of P53?
Assesses for cell damage halting division and if repair of DNA not possible stimulates caspases and initiates apoptosis
What happens if too little apoptosis occurs?
Cancers
Autoimmune diseases
What happens if too much apoptosis occurs?
Neurodegenerative diseases
What is pyknosis?
Cell shrinkage
