Mechanisms of Disease Flashcards
What is hypoxia?
Oxygen deprivation
What are diseases the result of?
Intrinsic/ genetic abnormalities
External/acquired factors
How tolerant are cells to hypoxia?
It depends on the cell type
Some neurones can only tolerate a few minutes
Dermal fibroblasts can tolerate a number of hours
What is ischaemia?
Loss of blood supply due to reduced arterial supply or venous drainage
What are the 4 causes of hypoxia?
Hypoxaemic: arterial content of oxygen is low, high altitude etc
Anaemic: decreased ability of Hb to carry oxygen
Ischaemic: interruption of blood supply
Histiocytic: inability to use oxygen in cells due to disabled oxidative phosphorylation enzymes
Name some physical agents which cause cell injury
Extremes of temperature, direct trauma, electrical currents, radiation, sudden changes in atmospheric pressure
What are some chemical agents and drugs which can cause cell injury?
Glucose or salt in hypertonic solution High oxygen conc Alcohol Poisons Insecticides
Give 4 causes of cell injury
Microorganisms
Hypersensitivity/ autoimmune disorders
Dietary deficiencies and excess
Genetic abnormalities
What are the four principal targets of cell injury?
Cell membranes
Nucleus
Mitochondria
Proteins
Describe the events which occur in reversible hypoxic injury
Levels of ATP drop due to reduced oxidative phosphorylation
Sodium potassium pump fails, sodium builds up inside the cell, organelles swell up. Calcium also comes in damaging cell components
Cell switches to glycolytic pathway, produces lactic acid, reducing the pH, affecting enzyme activity, causes chromatin clumping
Ribosomes detach from ER, disrupts protein synthesis, intracellular accumulations of denatured proteins and fat
How does irreversible hypoxic injury usually appear?
Necrosis
Describe the key event in irreversible hypoxic injury?
Disturbances in membrane activity, rise in cytosolic calcium, this activates ATPases, proteases, endonucleases
Lysosomal enzymes are released
Intracellular substances leak out into blood, eg transaminases
What is ischaemia reperfusion injury?
Blood flow returned to a tissue that has been subject of ischaemia but is not yet necrotic
Sometimes makes injury worse
Potentially free radicals, lots of neutrophils, complement activation
How can free radicals damage cells?
Lipid peroxidation
Damage proteins and nucleic acids
Mutagenic
How are hydroxyl radicals formed?
Radiation directly lyses water
Fenton and Haber Weiss reactions
What is the fenton reaction?
Iron and hydrogen peroxide make hydroxyl radicals
What is the Haber Weiss reaction?
H+ and superoxide and hydrogen peroxide
Oxygen, water and hydroxyl radicals
What is oxidative stress?
An imbalance between ROS production and free radical scavenging
What makes up the anti oxidant system?
Enzymes such as SOD, catalase, peroxidases
Vitamins A, C, E
Storage proteins like transferrin sequester transition metals which catalyse free radical formation
What is the role of heat shock proteins?
They refold proteins which are denatured
What are the three main alterations that can be seen under a light microscope in cell injury?
Cytoplasmic changes
Nuclear changes
Abnormal intracellular accumulations
What are the reversible changes seen under a light microscope with cell injury?
Reduced pink staining initially due to accumulation of water
Subtle clumping of chromatin
Irreversible changes seen under a light microscope with cell injury
Later more pink staining of the cell due to detached ribosomes and denatured proteins
Pyknosis (shrinkage), karryolysis (dissolution), karryohexis (fragmentation) of the nucleus
What is oncosis?
The spectrum of changes that occur in an injured cell prior to death
What is necrosis?
The morphological changes which occur after cell death in a living tissue, largely due to the progressively degradative action of enzymes
Apoptosis
Programmed cell death induced by a regulated intracellular program where a cell activates enzymes which degrades its own nuclear DNA and protein
