Session 1 - Cell Injury Flashcards
What is hypoxaemic hypoxia?
Arterial concentration of oxygen is reduced
What is Anaemic Hypoxia?
Decreased ability of Hb to carry oxygen
What is Ischaemic Hypoxia?
Interruption of blood supply
What is Histiocytic Hypoxia?
Inability to utilise oxygen
Apart from hypoxia, what else can cause cell injury do death? (Long list)
- Physical agents
- Chemical agents
- Micro-organisms
- Immune mechanisms
- Dietary insufficiency
- Genetic abnormalities
What are the four main targets for cell injury?
- Cell membranes (both plasma and organeller)
- Nucleus
- Proteins
- Mitochondria
What is the general outline for hypoxia cell injury?
Cell is deprived of oxygen - No ATP production - Sodium potassium pump stops working - Sodium and water enter cell - Oncosis - pH decreases due to glycolysis - Calcium enters cell - Attacks on membranes, proteins, DNA and cytoplasmic comments - death
What is Ischaemia-Reperfusion injury?
Oxygen returns to Ischaemic tissue, causes damage if cells are not yet necrotic. Increase in free radicals, neutrophils and complement pathway
Name the three importance free radicals
- Superoxide
- Hydroxyl
- Hydrogen Peroxide
What are the bodies defences against free radicals?
- Enzymes - SOD, catalases and perioxidases
- Free radical scavengers - glutathione, Vit A,C and E
- Storage proteins - sequest transition metals
What are Heat shock proteins?
Proteins that recognise and repair mis-folded proteins
E.g Ubiquitin
What cytoplasmic changes can we see with light microscopy?
- decrease in pinkness = accumulation of water
- increase in pinkness = accumulation of denatured proteins and ribosomes
What nuclear changes can we see with light microscopy?
- Clumped chromatin
- Pyknosis - shrinkage
- Karryohexis - fragmentation
- Karryolysis - dissolution
What reversible changes can be seen with electron microscopy?
- Swelling
- Blebs
- Clumped chromatin
- Ribosome separation from ER
What irreversible changes can be seen with electron microscopy?
- Big cell swelling
- Nuclear changes
- Membrane defects
- swollen mitochondria
What is Oncosis?
Cell death with swelling
What is Apoptosis?
Cell death with shrinkage
What is Necrosis?
Morphological changes that occur after a cell has been dead for some time
What are the four types of necrosis?
- Coagulative
- Liquifactive
- Caseous
- Fat
What is Coagulative necrosis?
- More desaturation of proteins that release of proteases
- Solid consistency
- Appears white
- Proteins become less soluble
What is Liquifactive necrosis?
- more enzyme degradation that denaturation
- neutrophil infiltration
- seen in bacterial infections
- seen in brain
- viscous mass
When is Caseous necrosis seen?
In tuberculosis; amorphous debris with cheesy appearance
What is Fat necrosis?
- destruction of adipose
- Can be caused by acute pancreatitis = lipase release
- also from direct trauma
- in breast tissue can be confused for cancer
What are the two types of gangrene and how are they caused?
Dry - exposure to air
Wet - infection with bacteria
What is Infarction?
- Cause of necrosis, namely ischaemia
- Caused by thrombosis of embolism
- can also be through external compression of blood vessels
What is a White infarct?
- occurs in solid organs after occlusion of end artery
- Limits to amount of haemorraging that occurs
What is a red infarct?
Extensive haemorrhage into dead tissue, occurs when:
- Dual blood supply eg lungs
- Numerous anastomoses eg intestine
- loose tissue eg lung
- where previous congestion has occurred
- where there is raised venous pressure
What affects the consequences of the infarct?
- Whether tissue has an alternative blood supply
- How quickly ischaemia developed
- how vulnerable tissue is to hypoxia
What three molecules are released after cell injury?
Potassium, Enzymes and Myoglobin
What is special about DNA breakdown in apoptosis?
It is not random, it is cut in specific places
When does apoptosis occur?
- Can be a normal physiological process
- Can be hormone controllers
- cytosol T-cells killing virally infected cells
- cell damage especially if to DNA
Which organelle is the central player for intrinsic apoptosis?
The mitochondria
What is external apoptosis triggered by?
External Ligands such as TRAIL and Fas
What can we see in electron microscopy in apoptosis?
- Cytoplasmic budding
- Fragmentation
- No league of cellular contents
What can we see under a light microscope in apoptosis?
- Shrunken cells
- Chromatin condensation
- Pyknosis and Karryorrhexis
- Affects on only single cells or small clusters
Name some important apoptotic molecules (long list)
- p53; mediates response to DNA damage
- Cytochrome c, APAF 1 + cascade 9
- Bel-2 - prevents cytochrome c release
- TRAIL - death ligand
- TRAIL-R - death receptor
- Caspases
Name the 5 main groups of intra cellular accumulations
- Water and electrolytes
- Lipids
- Proteins
- Pigments
- Carbs
How can fluid accumulation appear in cells?
Either as small vacuoles or as Hydropic swelling
Where is Hydropic swelling most dangerous?
The brain; it does not have room to expand and can cause pressure on the blood vessels
What are the two types of lipid accumulation?
Steatosis and Cholesterol
What are two main types of protein accumulation?
Mallory’s Hyaline - damaged protein in hepatocytes due to alcohol liver disease
Alpha-1-antitrypsin - Mis-folded protein accumulates in ER and means no regulation of proteases in lung so can cause emphysema
Where are exogenous pigment residues found?
Lung and Lymph Nodes
Name three endogenous pigments
Lipofuscin, Haemosiderin, and Bilirubin
What is Lipofuscin?
Brown pigment found in ageing cells, found in long-living cells
What is Haemosiderin?
An iron storage molecule, most commonly found in bruising. Also very common in Hereditary Haemochromatosis where Iron absorption in the intestine is increased. (Treated with regular bleeding)
What is Bilirubin?
Bright yellow bile pigment
If levels too high = Jaundice
Transported to liver to be excreted
Name the two types of Pathological Calcification?
Dystrophic and Metastatic
What are the two main causes of Metastatic Calcification?
- Increased PTH release
- Destruction of bone
Why can cells not divide indefinitely?
- Accumulative damage of cell comments and DNA
- Shortened telomeres
What enzyme do stem cells and cancer cells have enabling them divide continually?
Telomerase
What are the three main effects on the liver as a result of chronic excess alcohol intake?
- Fatty change
- Acute alcohol hepatitis
- Cirrhosis
What is hypoxia?
Deficiency of oxygen reaching the tissues
