Pathology - Cell Injury/Death Flashcards
What are the 3 Cellular Responses that can occur as a result of Cellular Stress?
Adaption
Reversible Cell Injury
Irreversible Cell Injury/Death
What is Adaption?
the cell tries to adapt to changes in the environment by adjusting its phenotype
What is hypertrophy? 2 types
no new cells, cells increase in size
occur physiologically
- body building, muscle fibre increases
occur pathologically
- cardiac hypertrophy from the increase of myocyte size
- from stress and high BP
What is Hyperplasia? 2 types.
increased numbers of cells usually from hormones or growth factors, organ size increase
occur physiologically
- hormonal e.g. breast in pregnancy
occur pathologically
- benign tumours
NOT NEOPLASIA - NOT UNCONTROLLED CELL GROWTH
What is Atrophy? 2 types.
decrease in cell size and number, organ size decreases
physiological
- post partum uterus
pathological
- decrease workload - waste away
- denervation - no nerve supply
- no blood supply
- inadequate nutrition
What is Metaplasia
one differentiated cell type is replaced by another - may be able to better withstand the environment
Give examples of Metaplasia for Adaption in the oesophagus, lungs and cervix
oesophagus
- GORD
- acid reflux
- squamous cells
- into gastric-like columnar epit. cells
= Barretts Oesophagus
lungs
- cigarettes
- usual columnar cells
- into squamous cells - more resistant
cervix
- vaginal ph drops
- usual columnar cells
- into squamous cells
basic causes of cell injury (8)
- oxygen deprivation HYPOXIA
- physical/environmental - trauma, heat, cold, radiation
- chemical agents - drugs
- infectious agents - virus, bacteria, parasite
- immunologic reactions
- genetic derangements
- nutritional imbalances - excess or deficiencies
- ageing
what does oxygen deprivation cause a decrease of?
less/no production of ATP
what can oxygen deprivation lead to?
- loss of blood supply
- ischaemia
- increase in carbon monoxide
What 6 Mechanisms are Responsible for Cell Injury?
A ROS Might Cause Modified DNA
- ATP Depletion
- Increase of ROS
- Mitochondrial Damage
- Entry of Ca2+
- Membrane Damage
- Protein Misfiling, DNA Damage
- 3 Purposes of ATP
membrane transport
maintain chemical gradient
protein, dna and rna synthesis
- how can atp production be impaired? (2)
mitochondrial damage
hypoxia
- What are the 3 Effects of ATP Depletion, expand on them.
na pump depletes
more anaerobic respiration
detachment of ribosomes
- Mitochondrial Damage can be Direct or Indirect. How?
direct - hypoxia, toxins, radiation
indirect - influx of Ca2+, oxidative stress, phospholipid breakdown
- Can mitochondrial damage be reversed?
early it can
if sustained, it becomes irreversible
- How does Mitochondrial Damage become Irreversible?
Necrosis or Apoptosis
- Describe Necrosis from Mitochondrial Damage (7)
DIRECT DAMAGE
- mitochondria gets damaged
- MPTP forms - mitochrondrial permeability transition pore
- impair oxidative phosphorylation
- ATP depletion
- increased production of ROS
- multiple cellular abnormalities
- necrosis
- Describe Apoptosis from Mitochondrial Damage/
INDIRECT DAMAGE
- increase pro-apoptotic proteins
- decrease anti-apoptotic proteins
- mitochondrial proteins leak
- apoptosis
- How do you get a Calcium Pump Failure?
from hypoxia/toxins
- lack of ATP
- should the levels of regular cystolic calcium be high or low?
low
- what happens if there is calcium pump failure?
- release of calcium from mitochondria
- increase of membrane permeability
- calcium into the systole
- why is it bad for there to be increase calcium within the cell?
activation of harmful intracellular enzymes
- give 3 harmful intracellular enzymes and 3 effects
ATPases - ATP into ADP
phospholipases - cleave ester bond within phospholipids - lipid products are generated
endonucleases - cleave phosphodiester bond within polynucleotide chain - cut DNA
LESS ATP
DISRUPT CELL MEMBRANE
DNA DAMAGE
- what are free radicals?
single unpaired radical
- what is a ROS?
Reactive Oxygen Species
- increased ROS lead to..
oxidative stress
- how is oxidative stress caused?
increased production of ROS
- how can ROS come about? (4)
- ionising radiation
- ischaemia reperfusion injury
- metals (iron/copper) or chemicals (CCl4)
- nitric oxide - leads to inflammation
- what is ischaemia reperfusion injury
the death and dysfunction of cells after blood flow is restored to previously ischaemic tissues
- what does ROS do in the cell? (3)
- damage cell membrane
- break nucleic acid
- protein oxidation and fragmentation
- which three ways can membrane be damaged?
direct - bacteria, virus, immune proteins
indirect - increase calcium, ros, decrease ATP
lysosomal membrane damage - auto-digestion
- what can protein misfolding lead to?
ER stress
- what does ER stress end in?
apoptosis
What 2 Microscopic Features do you see in REVERSIBLE CELL INJURY?
- cellular swelling
- fatty change
what does ultrastructural mean?
the biological structure not visible through ordinary microscope
What 4 Ultrastructural Features do you see in REVERSIBLE CELL INJURY?
- plasma membrane bulge
- mitochondria swells
- ER dilates
- chromatin clumps
what are the two main forms of cell death?
apoptosis
necrosis
describe apoptosis - contents and inflammation
programmed cell death
cell contents contained
no surrounding inflammation
5 Instances of Physiological Apoptosis’ and what happens
Embryogensis - removal of unwanted cells during development
Hormone Withdrawal
Cell Turnover
Harmful self-reactive lymphocytes
death of host cells after immune response
4 Instances of Pathological Apoptosis
from DNA damage - radiation/drugs/free radicals
accumulation of misfolded proteins
Infections - direct or indirect
Pathological Atrophy
Give 2 Pathways for Apoptosis.
mitochondrial intrinsic pathway
death receptor extrinsic pathway
Describe Mitochondrial Instrinsic Pathway - Apoptosis
- DNA damage
- pro-apoptotic proteins leak
- caspases activate
- fragmentation of contents
= apoptotic bodies - engulfed by phagocytes
- broken down
Describe Death Receptor Extrinsic Pathway - Apoptosis
- extrinsic ligand binds to cell surface receptor
- activates caspases
- fragmentation of contents
= apoptotic bodies - engulf by phagocytes
- break down
Under a microscope, how does apoptosis appear?
- cell shrinks
- chromatin condenses
- cytoplasm blebs - blisters
- no surrounding damage
describe necrosis - contents and inflammation
membrane breakdown
- contents leak
- inflammation
compare necrosis to apoptosis in terms of: cell size, nucleus, plasma membrane, nearby inflammation, physiological or pathological
Give 6 Types of Necrosis
CCCGFF
Coagulative
Colliquative
Caseous
Gangrene
Fat
Fibrinoid
Where does Coagulative Necrosis Occur, how does it appear?
tissues with connective tissue e.g. heart
- the shape/structure is still preserved
Where does Colliquitive Necrosis Occur, how does it appear?
tissues with minimal connective tissue e.g. brain
- the shape liquefies
Where does Caseous Necrosis Occur, how does it appear?
usually see in an abscess or granulomatous inflammation
- cheese-like necrotic debris in a defined border
Where does Gangrene Occur, what are the 3 types and how they arise?
it is coagulative necrosis but of a limb
dry gangrene - coagulative necrosis sterile
wet gangrene - with infection
gas gangrene
Where does Fat Necrosis Occur and why does it appear?
specific pattern necrosis in fat
- due to action of lipases or traumatic injury to the fat
Where does Fibrinoid Necrosis Occur, how does it appear?
specific necrosis when damage to vessel walls
- get a pink material deposited in the vessel wall
How Clinical Diagnosis’ be Reached from Necrosis or Apoptosis e.g. myocardial infarction, pancreatitis
Myocardial Infarction
- myocardial enzymes released into blood e.g. Troponin
- this then acts as a biomarker for diagnostic tests
pancreatitis
- necrosis
- enzymes released into blood
= more amylase
= more lipase
- leads to saponification = less Ca2+ in the blood
Apoptosis can be seen microscopically
