Session 1 Flashcards
What are the different causes of hypoxia?
Hypoxaemic - arterial content of O2 is low (eg altitude)
Anaemic
Ischaemic - interruption of blood supply
Histiocytic- inability to utilise O2 (eg cyanide poisoning)
What are common methods of cell injury?
Hypoxia
Physical agents (trauma, heat, cold, radiation)
Chemical agents (poisons, alcohol, drugs)
Microorganisms
Immune mechanisms (autoimmune/hypersensitivity)
Dietary insufficiencies/excesses
Genetic abnormalities
What are the targets for cell injury?
Cell membranes, nucleus, proteins, mitochondria
Describe the reversible cell changes due to hypoxia
Production of ATP decreases. Activity of Na/K ATPase decreases, Na in the cell increases leading to swelling (oncosis).
Increased amount of glycolysis for ATP, decreasing pH through the production of lactic acid. Enzyme activity is affected and chromatin clumping is seen.
Ribosomes detach from the ER (usually requiring energy) and protein synthesis is depleted. Leads to accumulation of denatured proteins.
Describe the irreversible changes due to hypoxia
Cells die by oncosis and tissues will appear necrotic.
There is an increase in membrane permeability leading to a massive increase in cytosolic Ca2+. Several enzymes are thus activated (ATPase, endonucleases, proteases, phospholipases).
Lysosomal membranes are damaged which leak enzymes and further damage cell.
What is ischaemia reperfusion injury?
If blood flow is returned to an ischaemic tissue that is not yet necrotic the damage could be worse than if it wasn’t restored (eg more ROS produced)
What is the function of heat shock proteins?
They are concerned with protein repair in injured cells. They either correct misfolded proteins or destroy them using ubiquitin.
What are the structural changes of an injured cell seen under an electron microscope?
Reversible:
-swelling of cell and organelles due to Na/K pump failure
-Cytoplasmic blebs (bumps on membrane surface where cytoskeleton has detached)
-clumped chromatin due to reduced pH
-ribosome separation from ER
Irreversible:
-nuclear changes
-membrane defects
-appearance of myelin figures (damaged membranes)
-amorphous densities in swollen mitochondria
What is oncosis?
Cell death with swelling. Commonly seen in hypoxia.
What is apoptosis?
Cell death with shrinkage, self regulated
What is necrosis?
The morphological changes that occur after a cell has died. Follows oncosis.
What are the two morphological appearances a cell can take when dying?
Oncosis - Cell swells while nucleus fades away by karryolysis (dissolution). Plasma membrane rupture. Passive.
Apoptosis - cell shrinks while nucleus become very dense and breaks up. Membrane integrity preserved. Active.
What are the different types of necrosis?
Coagulative and liquefactive (main) and caseous and fat.
What is Coagulative necrosis and where is it seen?
Protein denaturation is the dominant feature over release of active enzymes. Denatured proteins then coagulate (solid white consistency). Cellular outline somewhat preserved. Seen in solid organs where there has been an infarct (eg heart).
What is liquefactive necrosis and where is it seen?
Release of active enzymes is the dominant feature over protein denaturation. Tissue is lysed and disappears (liquifies). Seen in infarct of the brain and infections.
What is caseous necrosis and where is it seen?
Characterised by amorphous (structure less) debris - “half way” between liquefactive and Coagulative. Particularly associated with infections - especially TB.
What is fat necrosis and where is it seen?
Occurs when there is a destruction of adipose tissue, such as in acute pancreatitis where there is a realise of lipases and in direct trauma to fatty tissue (eg breast).
What is gangrene and what are the different types?
Clinical term for grossly visible necrosis.
Dry gangrene - necrotic tissue modified by air, Coagulative, eg umbilical cord after birth.
Wet gangrene - infected necrotic tissue, can lead to septicaemia, liquefactive
Gas gangrene - wet gangrene that has become infected by clostridium perfringens, producing visible bubbles of gas
What are the two different types of infarct and where are they found?
White - occurs in solid organs after occlusion to an end artery (e.g. Heart, spleen and kidneys). Most are wedge shaped and appear as Coagulative necrosis.
Red - occurs when there is extensive haemorrhage into dead tissue (e.g. Gut, lung). Due to a dual blood supply, numerous anastomoses or venous insufficiency.
What can cause an infarct?
Thrombus/embolism (most) or external compression or twisting of vessels.
What does the consequences of an infarct depend on?
Alternative blood supply
How quickly the ischaemia occurred
How vulnerable the tissue is to hypoxia
The oxygen content of the blood
What are the principal molecules released by an injured cell?
Potassium - stops heart in high concentrations
Enzymes - indicates the organ involved and extent of injury
Myoglobin - from dead myocardium/striated muscle
What are the methods of hydroxyl production?
Radiation, Fenton and Haber-Weiss reactions
What happens to DNA during apoptosis?
Characteristic, non random cleavage
