Cell Injury Flashcards
Define Hypoxia
A state of oxygen deprivation
What are the four causes of hypoxia?
Hypoxaemic hypoxia
Anaemic hypoxia
Ischaemic hypoxia
Histocytic hypoxia
What is Hypoxaemic Hypoxia?
Low arterial oxygen content
Possible causes:
- high altitudes
- reduced oxygen absorption due to lung disease
What is Anaemic Hypoxia?
Deceased oxygen carrying ability of oxygen
Possible causes
- Anaemia
- CO poisoning
What is Ischaemic Hypoxia?
Interruption to blood supply
Possible causes
- Blockage of a vessel
- Heart failure
What is Histocytic Hypoxia?
The inability to use oxygen due to disabled oxidative phosphorylation enzymes
Possible causes
- cyanide poisoning
Give examples of toxins that can cause cell injury
High concentration of oxygen - promotes free radical formation
Medicines - e.g. chemotherapy
Narcotic Drugs
Pollutants
Glucose and Salt in hyper-tonic solutions
How can heat injure cells?
Heat can cause proteins to unfold. Cells exposed to heat release heat shock proteins which try to mend these misfolded proteins
List some other causes of cell injury
Cold
Trauma
Radiation
Micro-organisms - e.g bacteria, viruses, fungi, parasites
Immune mechanisms - hypersensitivity, autoimmune diseases
Explain hypersensitivity
overly vigorous immune reaction results in accidental destruction of host cells
Explain Autoimmune diseases
Failure to distinguish self cells from non-self cells
What are the principal structural targets for cell damage?
Plasma Membranes Organelle Membranes - e.g. lysosomes Nucleus - specifically DNA Proteins - structural and enzymes Mitochondria
What are the features of reversible hypoxia?
Decreased ATP production which leads to:
- loss of activity of sodium potassium pump
- anaerobic respiration
- ribosomes detach from ER and protein synthesis is disrupted
Explain the effects of loss of the sodium-potassium pump
Intracellular Na+ concentration rises
Water enters cell
Cell and organelles swell
Ca2+ enters and damages the cell components
Explain the effects of anaerobic respiration
Build up of lactic acid
Decrease pH
Affects enzyme activity
Chromatin Clumping
Explain the effects of the ribosomes detaching
Intracellular accumulation of fat, denatured proteins etc.
What happens in irreversible hypoxia?
Development of profound disturbances in membrane integrity
Accumulation of cytosolic Ca2+ through entering the plasma membrane of damaged cells and by being released from intracellular stores
What are the effects of increased cytosolic Ca2+?
Activates ATPase, further decreasing ATP concentration
Activates phospholipases resulting in more damage to the membrane
Activates proteases which breakdown the membrane and cytoskeleton
Activates endonucleases which damage DNA
What is Ischaemic-Reperfusion Injury?
Blood flow returned to an ischaemic tissue that is not yet necrotic
What are the effects of Ischaemic-Reperfusion Injury?
Increased production of oxygen free radicals
Increased neutrophils leading to more inflammation so increased tissue injury
Delivery of complement proteins and activation of the complement pathway
How can free radicals cause cell injury?
Attack lipids in membrane, causing lipid peroxidation
Damage proteins and nucleic acids (i.e. mutagenic)
React with other molecules to make more free radicals
What are free radicals?
Molecules with a single, unpaired electron
Important in cell signalling
Produced by leukocytes to kill bacteria
Give three examples of free radicals
Hydroxyl (OH’)
Superoxide (O2-)
Hydrogen Peroxide (H2O2)
Describe the three ways in which hydroxyl ions can be produced
Radiation - lyses water to OH’
Fenton reaction (uses Fe3+)
Haber-Weiss Reaction (uses superoxide and hydrogen peroxide)
Define oxidative stress
Imbalance between free radical production and free radical scavenging
What are the components of the anti-oxidant system?
SOD enzyme - catalyses superoxide into hydrogen peroxide
Catalases and Peroxidases - catalyse hydrogen peroxide into oxygen and water
Free Radical Scavengers
Storage Proteins
Name some free radical scavengers
Vitamins A,C and E
Glutathione
How do storage proteins work?
They sequester transition metals that catalyse the formation of free radicals
Define oncosis
Cell death with swelling
Define Necrosis
Morphological changes that follow cell death in living tissue
Define Apoptosis
Cell death with shrinkage
What changes that occur in cell injury are visible with a light microscope?
Cytoplasmic changes
Nuclear Changes
Abnormal intracellular accumulations
What reversible changes are visible with an electron microscope?
Swelling of the cell and its organelles
Cytoplasmic blebs
Clumped Chromatin
Ribosome separation from ER
What irreversible changes are visible with an electron microscope?
Further Cell Swelling
Nuclear changes - pyknosis, karyolysis and karyorrhexis
Swelling and rupture of lysosomes
Membrane defects
Appearance of myelin figures
Lysis of ER
Amphorous densities in swollen mitochondria
