2, 3.1, 3.2. Cell adaptations, Acute inflammation, chronic inflammation

2. Cell adaptations
1. Cell adaptations
1. Hypertrophy – Increase in cell size (Muscle in athletes, prostate)
2. Hyperplasia – Increase in cell number (Bone marrow in high altitudes, psoriasis)
3. Atrophy – Decrease in cell size/number (post-menstrual uterus, immobile limb/no blood supply)
4. Metaplasia – Transformation one mature cell type to another (Smokers trachea – Pseudostratified columnar -> stratified squamous, barrett’s oesophagus – reflux squamous -> columnar)
2. Causes & targets of cell injury
Causes 1. Chemical, 2. Biological, 3. Glucose/oxygen deprivation
Targets 1. Cell/organelle membrane, 2. Metabolic processes, 3. DNA/proteins
3. Mechanisms of cell injury
1. Ischemia – Reduced blood flow
2. Hypoxia – Reduced oxygen supply
3. ROS
4. Ionising radiation
4. Reversible injury
-Hydropic degeneration – swelling, more eosinophilic
-Fatty change – presence of triglyceride-containing vacuoles
5. Autophagy – Digestion of cell’s own components as a survival mechanism e.g. starvation
6. Apoptosis vs necrosis
1. Cell shrinkage, cell swelling
2. Plasma membrane intact, plasma membrane disrupted
3. Cell contents intact, cell contents digested, may spill out
4. No adjacent inflammation, frequent adjacent inflammation
5. Often physiological, sometimes pathologic vs invariably pathologic
Apoptosis causes
1. Physiologic – Embryogenesis, turnover of highly proliferative cells, left over leukocytes after immune response
2. Pathologic – UV damage, infections
Apoptosis mechanisms
1. Intrinsic (mitochondrial)
-Pro-apoptotic genes (BAK/BAX)
-mitochondrial cell membrane permeable
-Cytochrome c leaks into cytoplasm
-Caspase activation
-Apoptotic enzyme activation
2. Extrinsic (Death receptor)
-When T-cells recognise the death receptor (Fas/TNF)
-Caspase activation
Macroscopic patterns of necrosis
1. Coagulative
-In most solid organs
-Tissue is initially preserved
-Characteristic of infarction
2. Liquefactive
-Brain infection & infarction
-Site replaced by cyst
3. Caseous necrosis
-Characteristic of tuberculosis infection
4. Fat necrosis
-Released fat & calcium results in soapy white chalks

3.1 Acute inflammation
1. 5 signs of inflammation
1. Dolor (pain)
2. Calor (Heat)
3. Rubor (redness)
4. Tumor (swelling)
5. Loss of function
2. 5 causes of acute inflammation
1. Microbes
2. Hypersensitivity
3. Physical agents
4. Chemical
5. Tissue necrosis
3. Acute inflammation process
1. Change in vessel calibre – Arteriolar walls form pre-capillary sphincters + Vasodilation
2. Increased vascular permeability – Capillary hydrostatic pressure increase + Escape of plasma proteins into extravascular space
3. Formation of cellular exudate
a. Margination of neutrophils (flow closer to vessel periphery)
b. Adhesion of neutrophils to endothelium
c. Emigration (neutrophils migrate between gaps in endothelial cells)
d. Migrate into adventitia
4. Chemotaxis of neutrophils to site of injury

Role of macrophages in acute – Secrete il-1, TNF alpha
Role of lymphatics – Drain edema, antigens carried to nodes for recognition
Role of neutrophils – Phagocytosis & intracellular killing
4. Chemical mediators in acute inflammation
1. Histamine
2. Chemokines
3. Prostaglandins
4. Leukotriens
3 Plasma derived mediators
1. Proteases
2. Kinins
3. Complements
5. Effects of acute inflammation
Good
1. Delivery of nutrients & oxygen
2. Fibrin formation
3. Stimulation of immune response
4. Toxin dilution
5. Transport of drugs
Bad
1. Digestioin of normal tissues
2. Swelling e.g. airway
3. Inappropriate immune response e.g type 1
6. Appearance of acute inflammation
-Serous, fibrinous, suppurative
7. Acute inflammation sequelae
1. Resolution (Phagocytosis of bacteria, fibrinolysis, phagocytosis of debris, disappearance of vascular dilation)
2. Suppuration
3. Repair & organisation
4. Fibrosis
5. Chronic inflammation
Factors leading to resolution
1. Minimal cell death & tissue damage
2. Organ/tissue has regenerative capacity
3. Rapid destruction of casual agent
4. Good vascular drainage
8. Systemic effects of both acute & chronic
1. Pyrexia
2. Weight loss
3. Haematological changes
4. Amyloidosis
5. Malaise, nausea

3.2 Chronic inflammation
1. 4 causes of chronic inflammation
1. Resistance of pathogen to phagocytosis e.g. Tuberculosis
2. Exogenous materials e.g. implanted prostheses
3. Autoimmune disease e.g. Rheumatoid arthritis
4.Granulomatous disease e.g. Crohn’s
2. Macroscopic appearances of chronic inflammation
1. Chronic ulcer
2. Chronic abscess
3. Thickening of hollow viscus wall
4. Granulomatous inflammation
5. Fibrosis
3. Microscopic appearance of chronic
1. lymphocytes, macrophages (because they live longer than neutrophils), plasma cells
2. Granuloma (collection of epitheloid histiocytes)
4. Causes of granulomatous disease
1. Bacteria, fungi, parasites
2. Materials that resist digestion
3. Drugs
4. Beryllium
5. Unknown e.g. Crohn’s

Leave a Reply

Your email address will not be published. Required fields are marked *