Session 1 Flashcards
What does persistent hypoxia lead to?
Cell adaptation, cell injury or death
What is ischaemia?
Loss of blood supply due to decreased arterial supply or reduced venous drainage
What is hypoxaemic hypoxia?
Hypoxia due to a decreased arterial oxygen concentration
What is anaemia hypoxia?
Hypoxia due to reduced ability of Haemoglobin to carry oxygen
What is Ischaemic hypoxia?
Hypoxia due to interruption of the blood supply
What is histiocytic hypoxia?
Hypoxia due to an inability to utilise oxygen in cells because of disabled oxidative phosphorylation enzymes
How does a hypersensitivity reaction cause cell injury?
Host tissue is injured secondary to an overly vigorous immune response
What cell components are the principal targets of cell injury?
- Cell membranes
- Nucleus
- Proteins
- Mitochondria
What occurs within a cell in reversible hypoxic injury?
- Oxygen deprivation causes reduction in ATP production
- Na/K pump stops as it is ATP-dependent
- Intracellular [Na] rises so water enters the cell
- Calcium enters the cell and has toxic effects
- Cell switches to glycolytic pathway of ATP production
- pH of cell lowers due to lactate production so enzyme activity is affected
- Ribisomes detach from ER so protein synthesis is disrupted
What is seen in a cell with reversible hypoxic injury?
- Cell appears swollen due to oncosis
- Chromatin clumping is seen
- Intracellular accumulations of fat and denatured proteins appear
What occurs in irreversible hypoxic injury?
- Cell is injured to a point where it will eventually die
- Usually die due to oncosis or disturbances in membrane integrity
- Massive influx of calcium into the cytoplasm
- Ca influx causes more Ca to be released from stores in the cell and activates enzymes to break down the cell components
What can be seen in cells with irreversible hypoxic injury?
- Blebbing due to reduced membrane integrity
- Tissue appears necrotic
- Chromatin clumping
- Cells with contents leaking
How does ischaemia-repercussion injury occur?
- Reoxygenation causes increased oxygen free radical production and increased neutrophils
- Causes increased inflammation leading to injury
- Complement proteins are delivered to activate the complement pathway
Why is the Fenton reaction particularly important where bleeding occurs?
Iron from the blood can be used in free radical production so more damage can be caused to the bleeding area
What mechanisms does the body use to prevent free radical damage?
- Anti-oxidant system
- Enzymes can remove free radicals
- Free radical scavengers neutralise free radicals
- Storage proteins sequester transition metals to prevent free radical formation catalysis
Which enzymes can be used to remove free radicals?
- Superoxide dismutase catalyses superoxide to hydrogen peroxide
- Catalases and peroxidase a catalyse hydrogen peroxide to oxygen and water
What molecules can act as free radical scavengers?
- Vitamins A, C and E
- Glutathione
What is the function of heat shock proteins?
Protect against cell injury by recognising misfiled do proteins and repairing them or destroying them
Give an example of a heat shock protein
Ubiquitin
What happens when a cell is injured with respect to heat shock proteins?
- Cell turns down protein synthesis is and turn up HSP synthesis in response to stress
- HSP recognises misfiled proteins within the cell and repairs them
- If a misfiled protein can be repaired it is destroyed
How can dead cells be distinguished using microscopy?
- Using the dye exclusion technique
- If dye enters a cell it is dead, if it doesn’t enter it is alive
What reversible changes occur histologically in cell death?
- Reduced pink staining in the cytoplasm due to oncosis
- Chromatin clumping
- Swelling of the cell and organelles
- Cytoplasmic blebs
- Ribosome separation from the ER
What irreversible changes occur in cell injury?
- Increased pink staining in the cytoplasm due to detachment of ribosomes from the ER and accumulation of denatured proteins
- Pyknosis, karryohexis and karryolysis of the nucleus
- Swelling and rupture of lysosomes
- Membrane defects
- Appearance of myelin figures from damaged membranes
- Lysis of ER due to membrane defects
- Amorphous densities in swollen mitochondria
What is oncosis?
Cell death with swelling
What is necrosis?
Morphological changes that occur after a cell has been dead some time
What causes necrosis?
Progressive degradative action of enzymes
What is dystrophic calcification?
Calcification of necrotic tissue which isn’t removed my enzymatic degradation and phagocytosis
What is coagulative necrosis?
Necrosis where denturation of proteins dominates over the release of active proteases
How does tissue which is undergoing coagulative necrosis appear?
Solid consistency and appears white to the eye
What occurs at a cellular level in coagulative necrosis?
- Cell proteins uncoil and become less soluble
- Cell architecture is mainly preserved so cells appear as a ghost outline histologically
- After a few days cells will incite an acute inflammatory response and are infiltrated by phagocytes
What occurs in cells undergoing liquefactive necrosis?
Enzyme degredation dominates over protein degredation so tissue becomes a viscous mass
How do tissues undergoing liquefactive necrosis appear?
- Viscous mass
- May be pus present if there is acute inflammation
Where is liquefactive necrosis typically seen?
- In massive neutrophil infiltration due to protease release
- In brain tissue to to lack of support from a robust collagenous matrix
Where is coagulative necrosis typically seen?
In most solid organs
What typically causes caseous necrosis?
- Infections; mainly TB
- Granulomatous inflammation
How does caseous necrosis appear?
- Looks cheesy to the eye
- Amorphous structureless debris present
- No ghost outlines of cells
What occurs in tissues with fat necrosis?
Adipose tissue is destroyed
When does fat necrosis occur?
- As a consequence of acute pancreatitis
- Due to direct trauma to fatty tissue; especially breast tissue
How does fat necrosis occur?
- Lipases are released and act on fatty tissue
- Free fatty acids are released
- F.A react with calcium to form chalky deposits in fatty tissue
What is hypoxia?
Oxygen deprivation
Activation of which enzymes causes chromatin clumping?
Endonucleases
What effect do neutrophils have in ischaemic-reperfusion injury?
Increased inflammation in the tissue which can cause increased injury
