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What is necrosis?

Necrosis is the death of tissues following bioenergetic failure and loss of plasma membrane integrity


What does necrosis do?

+ Pathological process

+ Often invokes an inflammatory response and repair

+ Often affects solid mass of tissue


What types of necrosis are there?

+ Coagulative
+ Colliquative
+ Caseous
+ Gangrene
+ Fibrinoid
+ Fat


What are features of coagulative necrosis?

+ The most common type

+ Involves coagulation of cellular proteins

+ Initially firm but later soft

+ Microscopically
-appearances develop over time
- ghost outlines of cells
- inflammatory response


What are features of colliquative necrosis?

+ In the brain

+ Liquefaction with formation of cystic spaces occurs

+ Proteolysis dominates over coagulation


What is caseous necrosis?

+ Characteristic of tuberculosis

+ There is pale yellow semi-solid material


What are features of gangrenous necrosis?

+ Necrosis with putrefaction
- wet and dry forms
- gas gangrene due to C perfringens

+ Follows vascular occlusion or certain infections

+ Black


What are features of fibrinoid necrosis?

+ Microscopic feature in arterioles

+ Most commonly associated with 'malignant' hypertension

+ Histological phenomenon


What are features of fat necrosis?

+ May occur following direct trauma and cause a mass,

+ May follow pancreatitis visible as multiple white spots (enzymatic lysis)

+ Related to death of fat cells


When does necrosis occur?

Necrosis occurs when a cell is damaged by an external force such e.g toxins, trauma, infection or ischaemia


What is apoptosis/PCD

The death of cells which occurs as a normal and controlled part of an organism's growth or development.


How does apoptosis differ from necrosis?

Necrosis is the premature death of living cells and tissues caused by factors external to the cell/tissue.

Apoptosis is programmed and a healthy, natural process:
+ removes a cell discreetly
+ takes our individual cells rather that groups of tissue
+ minimal fuss
+ preserves function as best as possible


What's the difference between apoptosis and Programmed Cell Death (PCD)?

Apoptosis is morphological; PCD is intent


Name some examples of apoptosis/PCD

+ Embryology: lumen of tubes
+ Growth signal response: menstrual cycle
+ Inflammation: resolution, death of neutrophils
+ Immune defence: T and Killer cell responses
+ Tumour prevention: prevent mutation
+ Autoimmune disease: self destruct
+ HIV/AIDS - HIV and activated T cell death


What are the types of abnormal apoptosis?

+ Reduced apoptosis

+ Increased apoptosis


Give examples of reduced apoptosis

+ Neoplasia

+ Autoimmune disease

+ Viral infection


Give examples of increased apoptosis

+ Neurodegenerative disorders

+ HIV infection of T lymphocytes


Apoptosis vs Necrosis: Induction

Apoptosis: physiological or pathological

Necrosis: pathological


Apoptosis vs Necrosis: Extent

Apoptosis: single cells

Necrosis: cell groups


Apoptosis vs Necrosis: Biochemical Events

Apoptosis: energy-dependent fragmentation of DNA

Necrosis: abnormal ion homeostasis


Apoptosis vs Necrosis: Cell Membrane Integrity

Apoptosis: maintained

Necrosis: lost


Apoptosis vs Necrosis: Morphology

Apoptosis: cell shrinkage and fragmentation

Necrosis: cell swelling and lysis


Apoptosis vs Necrosis: Inflammatory Response

Apoptosis: none

Necrosis: usual


Apoptosis vs Necrosis: Fate of dead cells

Apoptosis: phagocytosed by neighbouring cells

Necrosis: phagocytosed by inflammatory cells


What is pyroptosis?

+ Highly inflammatory form of programmed cell death

+ Occurs most frequently upon infection with intercellular pathogens

+ Likely to form part of the
antimicrobial response

+ Part apoptosis but then necrosis

+ Associated with Salmonella infection


What happens to cells after injury?

+ Death

+ Healing

+ Repair


What is healing?

The restitution with no/minimal residual defect

E.g superficial skin abrasion, incised wound healing by first intention


What is the difference between hearing and repair?

+ Healing is complete resolution

+ Repair is necessary when there is tissue loss: healing by second intention (second best option)


What three types of cell populations are there?

+ Labile

+ Stable

+ Permanent


What are features and examples of labile cells?

+ continuous regeneration

+ short lifespan

+ Skin, blood, gut


What are features and examples of stable cells?

+ Few divisions

+ Spend most of the time in the quiescent G0 phase of the cell cycle

+ Only multiply/repair when needed/ injured

+ Liver, Kidney, endocrine glands


What are features and examples of permanent cells?

+ Cannot regenerate once injured

+ Brain/neurones, skeletal muscle


What is organisation?

+ Repair of specialised tissue by formation of a scar


What does organisation involve?

+ Formation of granulation tissue

+ Removal of dead tissues by phagocytosis

+ Wound contraction and scarring


Describe the process of healing by first intention (wound with opposed edges)

1. Limited cell death
2. Basement membrane disrupted
3. Incisional space fills with blood
4. Scab forms
5. Neutrophils move towards the clot
6. Epidermis thinkers at its cut edges
7. Epidermal cells migrate among cut margins if the dermis
8. Epithelial cells fuse in midline beneath surface scan
9. Day 3 neutrophils largely replaced by macrophages
10. Day 5 granulation tissue invades incision space
11. Collagen fibres bridge the incision
12. Epidermis recovers to normal thickness


What happens during the second week of healing by first intention? (Wound with opposed edges)

+ Proliferation of fibroblasts

+ Collage accumulation

+ Leucocytes infiltrate, oedema reduced

+ Vascularity virtually disappeared


What happens by the end of the first month of healing by first intention? (Wound with opposed edges)

+ Scar consists of cellular connective tissue

+ Tensile strength now increases


Describe healing by second intention (wounds with separated edges) compared to first intention

+ Extensive cell loss
+ Common denominator is large tissue defect that must be filled
+ Large defects
- more fibrin
- more necrotic tissue
- inflammatory reaction more intense
+ Much larger amounts of granulation tissue
+ Wound contraction plays an important role in reducing size of defect


What most clearly differentiated healing by first intention and healing by second intention?

Wound contraction


What are the stages of bone healing?

+ Repair

+ Remodelling

+ Resolution


What are the steps involved in liver healing/repair?

+ Necrosis

+ Regeneration

+ Fibrous scarring

+ Architectural disruption


What is the wound strength process?

+ Sutures removed end of week 1
+ Strength 10% of unwounded skin
+ Strength increases rapidly over the following 4 weeks
+ Rate of increase slows
+ By third month strength at 70-80%
+ Full strength may not be recovered


What are the systemic factors that influence wound healing?

AGE: delayed healing in old and very young

NUTRITION: affects proteins and collagen synthesis

METABOLIC STATUS: healing delayed in diabetics

CIRCULATORY STATUS: adequate blood supply essential

HORMONES: glucocorticoids are anti-inflammatory but impair collagen synthesis


What are the local factors that influence wound healing?

INFECTION: most important cause of healing delay

MECHANICAL FACTORS: early movement of wounds delays healing

FOREIGN BODIES: e.g sutures or glass

SIZE/LOCATION/TYPE OF WOUND: wounds heal better in richly vascularised areas


What are some types of abnormal wound repair?

+ Deficient scar formation
- dehiscence
- ulceration

+ Excessive formation of repair components
- keloid scar

+ Formation of contractures
- exaggerated contraction
- deformity if the wound and surrounding tissues


What are the effects of scarring?

+ Functionally imperfect

+ Provides permanent patch

+ Allows surrounding tissue to continue to function


What sort of problems might scarring cause?

+ Cosmetic

+ Functional
- site e.g stricture
- size e.g healed myocardial infarct


Define keloid scars.

Excessive fibroblast proliferation and collagen production.


What processes are involved in sublethal injury?

+ Hydropic change/ oncosis
+ Fatty change/ steatosis
+ Reversible

Over longer time:
+ Autophagy
+ Atrophy