Cell Injury Flashcards
Define hypoxaemic hypoxia
Arterial content of oxygen is low
What could cause hypoxaemic hypoxia?
Reduced inspired partial pressure of oxygen at high altitude
Reduced absorption secondary to lung disease
Define anaemic hypoxia
Decreased ability of haemoglobin to carry oxygen
Define ischaemic hypoxia
Interruption to blood supply
Define histiocytic hypoxia
Inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes
What are the main targets in cell damage?
Cell membranes
Nucleus
Proteins
Mitochondria
What is the pathogenesis of cell injury due to hypoxia?
Decreased oxidative phosphorylation, decreased ATP
Detachment of ribosomes
Na+-K+ pump disabled
Influx of calcium, water and Na+, efflux of K+
Leads to swelling, loss of microvilli, blebbing, ER swelling and myelin figures
Increased anaerobic respiration - decreased pH, chromatin clumping
What kinds of enzymes are activated by increased intracellular calcium?
ATPases
Phospholipase S
Proteases
Endonucleases
What are the 3 ways of generating hydroxyl ions?
Directly by radiation lysis of water
Fenton reaction (Fe2+)
Haber-Weiss reaction
Oxidative phosphorylation can yield which ROS?
Superoxide
Hydrogen peroxide
Which 2 enzymes act as antioxidants?
Superoxide dismutase
Catalase
What are the causes of ischaemic reperfusion injury?
Increased production of free radicals
Increased number of neutrophils - more inflammation and injury
Delivery of complement proteins and activation of the complement pathway
What are heat shock proteins?
Proteins that aim to mend misfolded proteins and maintain cell viability
Define pyknosis
Irreversible condensation of chromatin
Define karyorrhexis
Destructive fragmentation of the nucleus
Define karyolysis
The complete dissolution of chromatin due to endonucleases
Which cell injury changes are reversible?
Blebs General swelling Chromatin clumping ER swelling Detachment of ribosomes Mitochondrial swelling
Which cell injury changes are irreversible?
Defects in cell membranes Myelin figures Lysis of ER Rupture of lysosomes Pyknosis Karyorrhexis Karyolysis
Define necrosis
The morphological changes in a living organism that occur after a cell has been dead sometime.
What are the 2 main types of necrosis?
Coagulative
Liquefactive
What are the 2 special types of necrosis?
Caseous
Fat
Describe the features of coagulative necrosis
Denaturation of proteins dominates Ghost outlines Increased pink staining Many nuclei disappear Inflammation
Describe the features of liquefactive necrosis
Enzyme lysis of proteins dominates
Lots of neutrophils - pus
Lack of collagenous matrix present
Lots of swelling and inflammation
Describe the features of caseous necrosis
Contains structureless debris
No ghost outlines
Associated with infections (especially TB)
Describe the features of fat necrosis
Usually in abdomen but also in breast
Forms chalky deposits/calcium salts with tissue
Can be seen on X-rays
Result of pancreatitis (lipase release) or direct trauma to adipose tissue
What are the 2 types of gangrene and what defines them?
Dry - exposure to air
Wet - infection forming
What is gas gangrene?
A type of wet gangrene where anaerobic bacteria get under the skin and create bubbles of gas.
What does the degree of injury depend on?
Type of injury
Severity of injury
Type of tissue
The consequences of infarcts depends on …
Alternative blood supply
Speed of ischaemia
Tissue involved
Oxygen content of blood
If muscle is damaged, what is release and how do we know?
Myoglobin
Urine will be brown
What are the 3 phases of apoptosis?
Initiation, Execution and Degradation
Describe the intrinsic pathway of apoptosis
DNA damage leads to p53 activation
Increases mitochondrial permeability
Apoptosome generated
Cascade initiated
Describe the extrinsic pathway of apoptosis
Ligands bind to receptors on the cell surface to activated a cascade in the cell.
(Eg. TRAIL activates caspase-8)
Which molecules make up the apoptosome?
Cytochrome C
APAF 1
Caspase 9
What is the function of Bcl-2?
Prevents cytochrome C release from mitochondria so prevents apoptosis.
What is haemosiderin?
An iron storage molecule that forms when there is excess iron due to haemorrhage.
What occurs in haemosiderosis?
Deposition of iron throughout many organs
What happens in hereditary haemochromatosis?
Iron deposited in endocrine organs, associated with scarring and can lead to diabetes.
Which types of hepatitis are transmitted orally?
A
E
Which types of hepatitis are transmitted in blood?
B
C
