MOD S1&2 Cell Injury Flashcards
What is cell injury?
When the cell can no longer adapt to changes in its environment, it begins to show evidence of cell injury.
How may a cell be injured?
Hypoxia Toxins Heat Cold Trauma Radiation Microorganisms Immune mechanisms Dietary deficiency/insufficiency Genetic abnormalities
What are heat shock proteins?
Produced in response to cell injury due to heat
They refold denatured proteins correctly
Misfolded proteins are destroyed
What are the main targets of cell injury?
Cell membranes
Nucleus
Proteins
Mitochondria
What is ischaemia reperfusion injury?
When blood flow is reinstated to an area of ischaemic tissue, the damage sustained is worse that it would have been without circulation.
Define ischaemia
The interruption of blood supply
Name the types of hypoxia
Hypoxaemic
Anaemic
Ischaemic
Histeocytic
What is hypoxia?
Reduced O2
Often due to ischaemia
What are some reversible changes to cells caused by hypoxia?
Reduced oxidative phosphorylation Decreased pH Na accumulation Cell swelling Reduced protein synthesis due to ribosome detachment
Define oncosis
The spectrum of changes that occur in a injured cell prior to death
What are irreversible changes to cells brought about by hypoxia?
Accumulation of cytosolic Ca2+
Activation of certain enzymes - these result in cell death
Do all cells react the same way to ischaemia?
No
Eg nerve cells would last a few minutes in ischaemic conditions whereas fibroblasts could last for hours
What reversible structural changes may be seen in an ischaemic cell under an electron microscope?
Swelling Chromatin clumping Autophagy Ribosome dispersal Blebs
What are blebs?
Small bumps on the cell membrane where the cytoskeleton has detached
What irreversible effects may be seen with an electron microscope in an ischaemic cell?
Nuclear changes
Lysosome rupture
Membrane defects
Endoplasmic reticulum rupture
Define apoptosis
Programmed cell death
What are the stages of apoptosis?
Initiation
Execution
Degradation/phagocytosis
What are the two methods of initiation of apoptosis?
Intrinsic (mitochondrial)
Extrinsic
Name an inhibitor of apoptosis
Bcl-2
What is necrosis?
The changes which occur after cell death in living tissue
Name a death ligand and a death receptor (involved in extrinsic apoptosis)
Ligand: TRAIL
Receptor: TRAIL-R
What are caspases?
Important effector molecules of apoptosis eg caspase 3
What are the important mediators of apoptosis?
Cytochrome c, APAF, caspase 9
Give some examples of types of necrosis
Coagulative
Liquefactive
Fat
Caseous
Describe coagulative necrosis
More protein denaturation that enzyme release
Consistency of tissue remains solid
Cell structure is somewhat preserved, leaving a “ghost outline”
Tend to be due to infarcts (not in brain)
Describe liquefactive necrosis
More enzyme release than protein denaturation
Tissue becomes a viscous mass
Tissue is lysed and disappears
Tends to be due to infarction (eg in brain)
Also seen in massive neutrophil invasions
Describe caseous necrosis
Tissue appears amorphous
Halfway between coagulative and liquefactive
Describe fat necrosis
Occurs in cases of cell death in adipose tissue
The fatty acids released react with calcium to form chalky deposits (calcium soaps)
What is p53?
Very important protein in apoptosis
Mediates apoptosis in response to DNA damage
What is pathological calcification?
Abnormal deposition of calcium salts within tissues
What is gangrene? Give types.
The clinical term for grossly visible necrosis
Dry or wet
Name and briefly describe the types of pathological calcification
Dystrophic - occurs in areas of dying tissue. No abnormal serum calcium or calcium metabolism
Metastatic - occurs in normal tissues secondary to abnormal calcium metabolism
Define “dry” gangrene and give an example
Grossly visible coagulative necrosis
An example is the umbilical cord after birth
Give some examples of types of abnormal cellular accumulations
Normal cell constituents eg lipids, proteins
Abnormal substances eg minerals or abnormal metabolic bi-products
Pigments eg coal dust, bilirubin, tattoos
Describe “wet” gangrene
Clinical term for grossly visible liquefactive necrosis
What is an infarct? Name the types.
Necrosis due to ischaemia
Red or white infarct
Describe white infarcts and give an example of where one could occur
Caused by the occlusion of an end artery
There are no peripheral blood vessels
Therefore area is left completely without blood
Eg kidney
Describe red infarcts and give an example of where one could occur
Occlusion of blood vessels leads to build up of blood
All vessels haemorrhage at once
Increased pressure causes decreased blood flow
This causes ischaemia and red infarct
Eg bowel
What are the main effects of chronic excessive alcohol intake on the liver?
Fatty deposits (steatosis) - reversible, can cause hepatomegaly
Hepatitis - usually reversible, jaundice, tenderness and fever
Cirrhosis - irreversible hardening and shrinking of liver, sometimes fatal, occurs in 10-15% of alcoholics
What are the main effects of aspirin overdose?
Pulmonary alkalosis
Metabolic acidosis (caused by overcompensation to alkalosis)
Acute erosive gastritis
Describe hypoxaemic hypoxia and when it could occur
Arterial oxygen content is low eg at high altitudes reduced inspired pO2
Describe anaemic hypoxia and when it could occur
Decreased ability of haemoglobin to carry oxygen eg carbon monoxide poisoning
Describe ischaemic hypoxia and when it could occur
Interruption to blood supply eg blockage of a vessel
Describe histeocytic hypoxia and when it could occur
Inability to utilise oxygen due to disabled oxidative phosphorylation enzymes eg cyanide poisoning
How could ischaemia reperfusion injury be explained?
Oxygen free radical production
Neutrophils causing inflammation and tissue injury
Activation of the complement pathway
If there was TB in the lung, what is the most common type of necrosis?
Caseous
What could cause liquefactive necrosis?
Infection which draws neutrophils, which secrete proteolytic enzymes
What affects the colour of an infarct?
Colour depends on how much haemorrhaging occurred
Where is fat necrosis most commonly seen?
In pancreatitis when lipases are released
