Cell Injury And Death Flashcards
What 4 things does the degree of injury depend on
- Type of injury
- Severity of injury
- Duration of injury
- Type of tissue
What 7 things can cause cell injury
Hypoxia Chemical agents Physical agents Micro-organisms Immune mechanisms Dietary deficiencies/ excesses Genetic abnormalities
Name 5 physical agents that can cause cell injury
Direct trauma Extreme temperatures Pressure changes Electric currents Radiation
Compare Hypoxia and Ischaemia
Hypoxia- Low O2
Ischaemia- Low O2 AND other substances
Compare the 4 types of Hypoxia
Give one example of each
Hypoaxemic Hypoxia: Low O2 in arteries
High altitude
Anaemic Hypoxia: Decreased ability of Hb to carry O2
Anaemia or CO poisoning
Ischaemic Hypoxia: Interruption to blood supply
Vessel blockage
Histiocytic Hypoxia: Unable to use O2, due to disabled Oxidative phosphorylation enzymes
Cyanide poisoning
Explain 2 ways in which immune system can damage the body
- Hypersensitivity reactions: Overly vigorous immune reaction damages tissue
- Autoimmune reactions: Immune system fails to distinguish self from non-self
Which 4 cell components are most susceptible to injury
- Membranes (Plasma + Organellar)
- Nucleus (DNA)
- Proteins (Structural)
- Mitochondria (Oxidative phosphorylation)
In reversible Hypoxia, explain;
- Cellular swelling
- Decreased pH
- Decreased protein synthesis
Reduced Oxidative phosphorylation-> Reduced ATP
- Reduced ATP= Reduced Na Pump activity-> Influx of Ca, H2O, Na-> Swelling of cell
- Reduced ATP= Increased anaerobic glycolysis-> Increased [lactic acid]—> Reduced pH
- Reduced ATP= Ribosomes detachment-> Reduced protein synthesis
In irreversible hypoxia,
- How does cytosolic Ca increase
- Which 4 enzymes are stimulated and what is their effect
- Enters from Extracellular space, mitochondria, ER
- ATPase- Reduced ATP
Phospholipase- Less Phospholipids
Protease- Disrupted membrane
Endonuclease- Damages chromatin
Give 5 ways free radicals can be made in the body
- Normal metabolic reactions
- Inflammation
- Radiation
- Reaction with unbound metals
- Drugs/ chemicals
How do heat shock proteins protect the cell
Give on example of one of these
When damaged, these proteins ‘mend’ mis-folded proteins and maintain cell viability
Ubiquitin
What is Ischaemia-Reperfusion injury
Explain 3 causes
If blood flow is returned to a damaged, but not necrotic, damage can be worse than if blood flow wasn’t retuned
Possible causes;
- Increased production of free radicals with reoxygenation
- Increased neutrophil number-> More inflammation and tissue injury
- Delivery of complement proteins
In injured/ dying cells appear under a light microscope in hypoxia, explain the visible changes
- Cytoplasm swells, becomes more pink and watery
2. Nucleus shrinks ( Pyknosis) Nucleus fragments (Karyorrhexis) Nucleus dissolves (Karyolysis)
In hypoxia, what are the 3 cellular changes in order
- Cytoplasmic changes
- Nuclear changes
- Abnormal cellular accumulations
When looking through an electron microscope, Compare Reversible and Irreversible injury in terms of;
- Cell membrane
- ER
- Ribosomes
- Mitochondria
- Nucleus
- Reversible-Blebs. Irreversible- Myelin figures, defects
- Reversible- ER Swells. Irreversible- ER Lysis
- Reversible- Dispersion. Irreversible- Rupture
- Reversible- Swelling, small densities. Irreversible- Swelling, Large densities
- Reversible- Chromatin clumping. Irreversible- Shrinking, Fragmenting, Dissolving
Define Oncosis
Define Necrosis
When is necrosis seen
Oncosis: Cell death with swelling, changes prior to death
Necrosis: Morphologic changes in a living organism, after a cell has been dead some tome
- seen after 12 to 24 hours
Name the 4 types of Necrosis
Where do the main 2 types occur, Give 2 examples
Coagulative Necrosis: In solid organs (Heart, Liver)
Liquefactive/ colliquitive Necrosis: In loose tissues (Brain, lungs)
Caseous Necrosis
Fat Necrosis
Define Liquefaction
Compare Coagulative and Liquefactive
Liquefaction= enzymatic digestion
Coagulative: Protein denaturation, Ghost outline of cells remains
Liquefactive: Tissue digestion by enzymes
In caseous necrosis,
- What is seen under a microscope
- What it is associated with
- Appearance by the eye
- Amorphous debris
- Infections, especially TB
- Cheesy
In fat necrosis;
- Describe the appearance
- When and how does it occur
- Melted candle-like
2. Often, acute pancreatitis causes pancreatic lipase release
Define Apoptosis
Does it use ATP
What are the 2 types
Cell death with shrinkage, induced by a regulated intracellular program
Yes
Pathological and Physiological
When does Physiological Apoptosis occur
Give 3 examples
- To maintain a steady-state
- Hormone controlled involution
- Embryogenesis
when does pathological Apoptosis occur
- Graft VS Host disease
- Damaged cells (Especially DNA)
- Virus-infected OR Neoplastic cells
Name the 4 visible stages in apoptosis
Normal cell
Shrinkage, chromatin Condensation
Fragmentation/ budding
Apoptic bodies
Name the 3 PHASES in apoptosis
Initiation
Execution
Degradation and Phagocytosis
Compare the 2 mechanisms for apoptosis and which phases they trigger
What do they both result in
Intrinsic- Initiating signal from within cell
Extrinisc- Extracellular initiating signals
Initiation and execution
Activation of caspases (enzymes than mediate apoptosis)
Define Gangrene
Compare Dry and Wet gangrene
What type of necrosis are these
What is Gas gangrene
Necrosis visible to the naked eye
Dry: Necrosis modified by exposure to air- Coagulative Necrosis
Wet: Necrosis modified by infection- Liquefactive Necrosis
Gas: Wet gangrene where the infection is with anaerobic bacteria that produce gas
Define an Infarction
Define Infarct
Infarction: Necrosis caused by reduction in arterial blood flow
Infarct: An area of necrotic tissue which is the result of loss of an arterial blood supply
What are the 2 most common causes of infarction
Thrombosis
Embolism
What is a white Infarct called
Where does it happen
What shape are they
Anaemic Infarct
In solid organs, at end artery
Wedge shaped
What is a red Infarct called
Where does one occur
Haemorrhagic Infarct
Loose tissue
What is the range of consequences of an infarction
What 4 factors does this depend on?
None to death
Alternative blood supply
Ischaemia speed
Tissue involved
Oxygen content of blood
What 3 molecules are released by injured cells
Potassium
Myoglobin
Enzymes
What 5 types of molecules can accumulate in injured cells
- Water and electrolytes
- Lipids
- Carbs
- Proteins
- Pigments
When fluid accumulates in cells,
- What the type of swelling
- When does it occur
- What enters cell
- Hydropic swelling
- When Energy supplies cut off
- Na and H2O flood into cell
What is triglyceride accumulation called, where is it most often
What are 4 causes of lipid accumulation in cells
If mild, what are the symptoms
Hepatic Steatosis
Alcohol (Reversible)
Diabetes Mellitus
Obesity
Toxins
None
In what 2 conditions do proteins accumulate in a cell
Explain these
- Alcoholic liver disease, Mallory’s hyaline accumulates
- Alpha1 anitrypsin deficiency. Incorrectly folded “” protein (A protease inhibitor)
Name 2 exogenous pigments that accumulate in cells
How do phagocytes play a role
Carbon/ coal dust/ soot- Phagocytosed by alveolar macrophages
Tattoos- Phagocytosed by macrophages in dermis and remains
Inhalation of carbon leads to which 2 conditions
Anthracosis
Pneumoconiosis
Name 2 endogenous pigments that accumulate in cells
Haemosiderin (Iron storage molecule)
Bilirubin (breakdown product of heme)
When does Haemosiderin accumulate in a cell
Give one way this can occur
What is Haemosiderosis
When there is systemic or local excess of Iron
Bruising
Systemic Iron overload, so Fe deposited in organs
What is hereditary Haemochromatosis
Name 2 organs other than endocrine organs where Fe is deposited
Name 3 symptoms
A genetic disorder caused increased Fe absorption in intestine
Skin, Heart
Liver damage, Heart dysfunction, endocrine failures
Compare Dystrophic/ Metastatic calcification
Which is more common
Dystrophic: Abnormal localised deposition of Ca salts in tissues
Metastatic: Abormal systemic deposition of Ca salts in tissues
More common- Dystrophic
Where does Dystrophic calcification occur, give 3 examples?
Area of dying tissue, aging/ damaged valves, TB Lymph nodes
Why does Dystrophic calcification occur
No abnormality in Ca metabolism
Local change favours nucleation of hydroxyapatite crystals
Why does Metastatic calcification occur
Compare normal symptoms and lethality
Due to hypercalcaemia, secondary to disturbances In Ca metabolism
usually no symptoms, can be lethal
What are 2 causes of hypercalcaemia
- Increased secretion of PTH causing Bon resporption
- Destruction of bone tissue
Why can cells not keep diving forever
Telomere is shortened each division
When telomere is at critical length, cell can’t divide anymore
How do germ cells have the capability to keep dividing
Name 2 other cell types which can do this
Contain telomerase, which maintains original length of telomeres
Stem cells, Cancer cells
