Injury + adaptations

Causes of physiological + pathogical atrophy

Physiological	Pathological
Embryonic development	Ischaemia ( reduced blood flow )
Hormone withdrawal	Endocrine disorders
Ageing	Nerve damage
Lack of exercise	Lack of nutrition

How to cells adapt to an injury

Adaptation	Meaning
Hypertrophy	Increased cell + tissue size
Hyperplasia	Increased cell numbers
Atrophy	Decrease in cell + tissue size + numbers
Metaplasia	Change in cell differentiation  → equipped for environmental stress
Dysplasia	Distorted growth pattern  → pre-neoplastic → increased mitosis

What are the factors impacting disease development? 

Factor
Nature of injury	Cause  Duration  Severity
Nature of cell	Cell type  Labile: continuous proliferation ( e.g. skin/ gut/ bone marrow ) → susceptible to cancer  Stable: can proliferate but normally doesn’t ( e.g. liver/ kidney )  Permanent: little capacity to divide ( e.g. neurons/ heart cells )  Cell adaptability  Stage of cell cycle

What is the process of cell death ( necrosis ) ?

1. Cell injured 

2. Endoplasmic reticulum + mitochondria swelling 

3. Clumping of chromatin 

4. More severe versions of 2 + 3 

5. Membrane blebs 

6. Nuclear condensation 

7. Necrosis 

8. Cell membrane bursts

What are the different causes of cell death + injuries ?

Exogenous	Endogenous
Trauma	Anoxia
Infection	Antigen
Chemicals	Body chemicals
Radiation	Metabolic products e.g. urate crystals in joints → pain + loss of function

What are the patterns of cell death ?

Pattern	Mechanism	Cause	Bodily reaction
Apoptosis	Cells pump water out of themselves → cell shrinks → membrane bound apoptotic bodies	Programmed by body	No chemotactic/ inflammatory response
Necrosis	Cell swells → bursts + releases cell contents into extracellular space	Injury	Inflammatory response

What are the signs of inflammation? 

Siigns	Cause	Mechanism
Heat	Local vascular reaction	CHanges in blood vessels  Increased fluid from vessels  Increased leucocytes  → vascular + cellular response
Redness	Vessels dilate → redness of blood shown
Swelling	Fluids leak from vessels → dilute chemicals involved in injury
Pain + loss of function
Leukocytosis	Vessels become more permeable + chemical signals attract leukocytes to the injury site → increased no of leukocytes

What is the purpose of chemotaxis + cause ? 

	Detail
Purpose	Initiate vessel + cellular changes for acute inflammation
Cause	Chemokines + cytokines released at injury site
Result	Chemical gradient established → movement of inflammatory cells → highest conc of chemoattractant: injury site

What is the difference bwt acute + chronic inflammation + examples of harmful consequences ? 

	Length	Cause	Consequence
Acute	Short term	Immediate repair response to injury	Meningitis
Chronic	Long term	Ongoing tissue repair + destruction	Arthritis

How does wound healing happen on a cellular level ?

 

1. Blood clumping + clotting → prevent further blood loss 

2. Platelets form scabs with blood cells clotted + fibrin 

3. Inflammation + dilation of blood vessels to bring O2 + nutrients + leukocytes

How does minimal / extensive scarring occur ?  

	Process	Scarring
Healing by first intention	Scab development  Acute inflammatory response w/ neutrophil  Angiogenesis  → proliferation of new blood vessels  Granulation tissue( new connective tissue + blood vessels formed in wound healing )  fills wounds  (macrophages + activated fibroblasts put down collagen fibres ) Resolution/ organisation	Resolution  → no scarring
Healing by 2nd intention		Organisation  → scarring  → distortion of scar + white in colour → avascular ( blood vessels produced in angiogenesis is removed )

What is the role of macrophage in wound healing?

 

1. Ingests + kill microbes 

2. Digest cell debris 

3. Produce pro-fibrotic messenger molecules → stimulate fibrosis 

What is chronic fibrosis + examples ?

 

Chronic fibrosis happens when: 

1. Cause of injury persists 

2. Success in repair is not recognised 

3. Chronic inflammatory cell populations persist 

→ functioning tissue is replaced by fibrosis + scar tissue 

Liver cirhosis/ COPD ( chronic obstructive pulmonary disease ) —> chronic bronchitis/ emphysema/ pneumoconiosis