PP: Cell Injury Flashcards
What is Hypoxia?
deficiency in the amount of oxygen reaching the tissues
Name 4 causes of hypoxia and decribe them.
- Hypoxaemic hypoxia: low arterial content of oxygen
- Anaemic hypoxia: decreased ability of haemoglobin to carry oxygen
- Ischaemic hypoxia - interruption to blood supply
Ischaemic hypoxia: interruption to blood supply - Histiocytic hypoxia: inability to utilise oxygen in cells due to disabled
oxidative phosphorylation enzymes
What can cause Hypoxaemic hypoxia?
- Low atmospheric oxygen
- Reduced adsorption due to lung disease
What can cause Anaemic hypoxia?
- Anemia
- Carbon monoxide poisoning
What can cause Ischaemic hypoxia?
- Blockage of a vessel
- Heart failure
What can cause Histiocytic hypoxia?
- Cyanide poisoning
What can cause cell death?
- Hypoxia
- Physical agents (trauma, heat, cold, radiation)
- Chemical agents (theraputic drugs, alcohol)
- Microorganisms
- Immune mechanisms
- Dietary insufficiency and dietary excess
- Genetic abnormalities
What is Grave’s
disease of thyroid an example of?
An Autoimmune reaction - immune system fails
to distinguish self from non-self
Which 4 cell components are most susceptible to injury?
- Cell membranes
- Nucleus
- Proteins
- Mitochondria
What happens during reversible hypoxic injury?
There is not enough oxygen supplied to the cell, therefore once the remaining oxygen is used up no more ATP can be systhesised. This means the Na/K ATP pump no longer works which leads to a build up of sodium inside the cell. Hence, this causes the cell to swell, lowers the pH and disrupts protein synthesis .
What happens during irreversible hypoxic injury?
Cell membrane increases in permeability therefore there is an influx of toxic calcium. This activates destructive enzymes.
Name 4 disruptive enzymes.
- ATPase
- Phospholipase
- Protease
- Endonuclease
What are free radicals?
An atom with a single unpaired electron in an outer orbit – an
unstable configuration hence react with other
molecules, often producing further free radicals
Name the 3 free radicals that are of particular biological
significance in cells.
- OH*
- O2-
- H2O2
How are free radicals
produced?
- Metabolic reactions
- Inflammation
- Radiation
- Contact with unbound metals (mainly iron and copper)
- Drugs and chemicals
How does the body control free radicals?
- Anti-oxidant system: donate electrons to the
free radical – vitamins A, C and E - Enzymes neutralise free radicals
Name 3 enzymes which neutralise free radicals.
– Superoxide dismutase
– Catalase
– Glutathione peroxidase
What cellular structures are damaged by free radicals?
Oxidise proteins, carbohydrates and DNA become bent out of shape, broken or cross-linked resulting in them becoming Mutagenic and therefore carcinogenic
What is the role of heat shock proteins?
In cell injury heat shock response aims to ‘mend’
misfolded proteins and maintain cell viability.
What is Pyknosis?
The irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis.
What is karyolysis?
dissolution of a cell nucleus
What is Karyorrhexis?
the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm.
How does an injured cell appear under light microscopy?
Pale pink and swollen primarily, then as proteins clump it appears pinker
How does an injured cell appear under electron microscopy?
- Blebs
- Ribsomes dispersed from ER (no ATP to hold them on)
- Clumping of chromatin
- Swelling
Define Oncosis.
cell death with swelling, the spectrum of
changes that occur in injured cells prior to death
Define Necrosis.
the morphologic
changes that occur after a cell has been dead some
time
Define apoptosis.
Cell death with shrinkage, induced by a regulated intracellular program where a cell activates enzymes that degrade it’s own nuclear DNA and proteins
What are the 4 types of necrosis?
- Coagulative
- Liquefactive
- Caseous
- Fat necrosis
When does coagulative necrosis occur?
Solid organs
When does liquefactive necrosis occur?
loose tissue
What does coagultive necrosis look like?
Ghost outline as cellular architecture is somewhat preserved
What does liquefactive necrosis look like?
Enzyme degradation is substantially greater than denaturation therefore this leads to enzymatic digestion (liquefaction) of tissues.
gooey basically :///
What does caseous necrosis look like?
Contains amorphous debris
ASSOCIATED WITH TB!!!
Define Gangrene.
Necrosis visible to the naked eye
Define Infarction.
Necrosis caused by reduction in arterial blood flow
Define dry gangrene.
Necrosis modified by exposure to air
coagulative necrosis
Define wet gangrene.
Necrosis modified by infection
liquefactive necrosis
What is ischaemia-reperfusion injury?
Injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen
What are some possible causes of ischaemia-reperfusion?
- Increased production of oxygen free radicals with
reoxygenation.
– Increased number of neutrophils resulting in more
inflammation and increased tissue injury.
– Delivery of complement proteins and activation of
the complement pathway.
Name 3 molecules released by injured cells.
- Potassium
- Enzymes
- Myoglobin
Describe the difference between when physiological apoptosis occurs and when pathological apoptosis occurs.
Physiological: Hormone controlled, evident in embrogenesis of limb buds
Pathological: Cytotoxic T cell killing of virus-infected or neoplastic cells or graft versus host disease
What does apoptosis look like?
Condensation of a single cell followed by apoptic bodies.
Name the 3 stages in apoptosis.
- Initiation
- Execution
- Degradation and Phagocytosis
What 2 pathways can the Initiation and execution stages of apoptosis by triggered by?
- Intrinsic
2. Extrinsic
What does the triggering of intrinsic or extrinsic pathways of apoptosis result in?
Activation of caspases: Cause cleavage of DNA and proteins of the cytoskeleton
How is the intrinsic pathway
initiated and carried out?
- Initiating signal comes from within the cell - p53 protein is activated and this results in the outer mitochondrial membrane becoming leaky - Cytochrome C is released from the mitochondria and this causes activation of caspases
How is the extrinsic pathway
initiated and carried out?
- Initiated by extracellular signals One of the signals is TNFα – Secreted by T killer cells – Binds to cell membrane receptor (‘death receptor’) – Results in activation of caspases
Where do abnormal cellular accumulations come
from?
If a cell can’t metabolise something it will remain
within the cell
What can accumulate in
cells?
– Water and electrolytes – Lipids – Carbohydrates – Proteins – ‘Pigments’
Define dystrophic calcification of tissues.
Localised calcification of tissues
Define Metastatic calcification of tissues.
Generalised calcification of tissues
Where and why does dystrophic calcification of tissues occur?
- Occurs in an area of dying tissue
- Local change/disturbance
favours nucleation of
hydroxyapatite crystals
Why does metastatic calcification occur?
Hypercalcaemia (secondary to disturbances in
calcium metabolism)
What causes hypercalcaemia?
- Increased secretion of parathyroid hormone (PTH)
resulting in bone resorption - Destruction of bone
Can cells live forever?
Mostly no, Germ cells and stem cells contain an enzyme called
telomerase - maintains the original length of the
telomeres. In this way they can continue to replicate,
indefinitely.
