Lecture 4&5: Major subcellular responses to injury, patterns of necrosis, events following death, an physical injuries

Pathological Calcification - Dys (bad) trophic Calcification

1. Focal deposition of calcium at sites of cell injury and necrosis

ex: scars, caseous nodules, degenerated foci in leiomyomas

2. Rxn to tissue damage from medical device implantation

• Sequestration of erythrocytes in implant site

From cell injury/damage

Pathological Calcification - Metastatic Calcification

Deposition of calcium in normal tissue

• Renal failure

• Increased parathyroid hormone secretion

• Ca has a predication for the internal elastic lamina of arteries

Cellular Aging

1. Accumulation of mutations (DNA damage)

2. Replicative Sequence (telomere shortening)

3. Damage to proteins & organelles (free radicals)

Time course of cellular response

1. Acute: Rapid (seconds to minutes to hours)

• Edema & Neutrophils

2. Subacute: Intermediate (hours to a few days)

• Monocytes/Macrophages

3. Chronic: Slow (days)

• Monocytes/Macrophages

Reversible Injury - Swelling

First manifestation of cellular injury

Hydropic change or vacuolar change or cloudy swelling

Transudate vs Exudate

Transudate - Increase hydrostatic pressure

• Clear, watery, low protein pushed out of blood vessels

• System issues

• Pressure changes

Exudate - Decreased colloid osmotic pressure

• Cloudy, thick, high protein

• Local inflammation → widens gaps between cells in blood vessels

Reversible Injury - Fatty Change

• Fat is broken down for energy (ketone bodies)

Major patterns of tissue necrosis

Coagulation

Gangrenous

Liquefactive

Caseous

Aging signs

Lipofuscin pigment (cellular debris) and neurofibrillary tangles

• In heart & neurons → they don’t divide (non-mitotic)

Coagulation Necrosis

Architecture of tissue is preserved (first few days after death)

Firm tissue

Injury denatures structural proteins & enzymes → blocks proteolysis of dead cells

Leukocytes are recruited to digest dead cells (phagocytosis clears up debris)

Characteristic of infarcts (necrosis caused by ischemia) in all solid organs except brain

Gangrenous Necrosis

Limb that has lost blood supply & has undergone coagulative necrosis involving multiple tissue layers

• Changes to liquefactive necrosis when bacterial infection is introduced

Liquefactive Necrosis

Focal bacteria

Microbes stimulate rapid accumulation of inflammatory cells → enzymes of leukocytes liquefy the tissue

• Pus

• Hypoxic death of cells within CNS

Caseous Necrosis

Cheeselike

Tuberculosis infection

Tissue architecture is obliterated & cellular outlines are indiscernible

Often surrounded by macrophages & inflammatory cells

3 Cardinal body changes following death

1. Algor mortis

2. Rigor mortis

3. Livor mortis

Algor mortis

Decreased body temp

-1^oC/hour @ ambient temp (20^oC)

Rigor Mortis

Rigidity of body

Several hours after death

Caused by hydrolysis of muscle ATP → without ATP myosin molecules adhere to actin filaments → rigid muscles

Livor Mortis (AKA postmortem hypostasis)

Blood settles in the lower portion of the body → purplish/red discoloration of skin

• areas corresponding to where the body was at the time of death may appear dark red/purple with whiteish areas

• blood vessels become compressed and prevent hypostasis in those areas

Oxyhaemoglobin forms at the expense of reduced haemoglobin

Post Mortem Events - Autolysis

Spontaneous destruction of tissues by intracellular enzymes

Occurs in body after death

Post Mortem Events - Autolysis Putrefaction

Decomposition of organic matter (like proteins) by microorganisms → foul smell

Post Mortem Events - Postmortem Blood Clots

Clots formed in heart/large vessels after death

4 general types of PHYSICAL injuries

1. Abrasion

2. Contusion

3. Incision

4. Penetration

7 Head Injury Types

1. Skull trauma

2. Concussion

3. Edema

4. Cerebral contusion

5. Epidural hemorrhage

6. Subdural hemorrhage

7. Subarachnoid hemorrhage