Cell Injury and cell death Flashcards
Fancy name for cause of disease
Aetiology
Three main causes of disease
- Genetic
- Acquired
- Multifactorial
complete the boxes
Mechanisms of cell injury:
1. Mechanical _____ of cells
2. Insufficient ______
3. Blockage of _______ _____
4. Failure of membrane ___________
5. generation of _____ _____
6. Damage to _______
7. Release of _________ contents
- disruption
- energy
- metabolic pathways
- pumps
- free radicals
- DNA
- lysosomal
What are three mains sites of cellular damage?
- Mitochondria
- Lysosome
- Plasma Membrane
Neurones and cardiac muscle use ________ _______ and not glycolysis to make ATP. So, they need a lot of ______ and during ATP depletion, they can get hurt more easily than other cells = __________ ___________
oxidative phosphorylation
energy
selective vulnerability
cystolic free ________ levels are 10 fold lower than extracellular fluid and maintained by _________ dependent pumps. _______ and some ______ cause early release of calcium into cytosol.
calcium
ATP
Ischaemia
toxins
_______ _________ ________ (free radicals) accumulate when production of cells exceed the antioxidant defenses leading to _________ ________.
Reactive oxygen species
oxidative stress
Loss of capacity of _______ _________ to maintain ionic balance between compartments occurs as a consequence of cell injury. This especially affects the ________
plasma membrane
mitochondria
2 Main examples of reversible cell injury:
1. Reduced _______ __________ resulting in depletion of _________ energy _____
2. Cellular ____ caused by changes in ________ concentrations and water __________ = __________ __________
- oxidative phosphorylation, ATP, stores
- swelling, ion, influx, hydropic degeneration
What are the three main steps in the degeneration / necrosis of kidney?
- Acute hydropic change
- vacuolar degeneration in kidney tubules
- acute tubular necrosis
What are the three main morphologies of these in order?
- Acute hydropic change
- vacuolar degeneration in kidney tubules
- acute tubular necrosis
what is the common cause of non alcoholic fatty liver disease? NAFLD
Obesity
Name the three main boxes in this liver cell
What are two main examples of irreversible cell injury?
Necrosis and apoptosis
Classify necrosis and apoptosis
i) Catastrophic / programmed
ii) pathological / physiological
iii) Passive/ active
- Necrosis: Catastrophic + pathological + passive
- apoptosis: programmed + pathological and physiological + active
Fill the boxes
When large numbers of cells die, the tissue is __________
necrotic
What are the 5 main patterns of necrosis?
- Coagulative
- Liquefactive
- Caseous
- Fat Necrosis
- Fibrinoic Necrosis
Fill the boxes
Complete the renal infarction analysis
Complete the boxes on the differences in myocardial infarction
Complete the blanks
Fill in the blanks
Fill in the boxes
Fill
In apoptosis:
i) An energy dependent active process in which cells activate ______ ________
ii) These degrade the cells own _______ and nuclear and cytoplasmic proteins.
iii) Fragments of cells break off and cleared by ____________ without inciting an acute ________ response.
- intracellular enzymes
- DNA
- phagocytosis, inflammatory
Process of apoptosis:
1. Cell _________ and _______ condensation
2. Membrane _________
3. Nuclear ________
4. ___________ body formation
5. __________ of apoptotic bodies
- shrinkage, chromatin
- blebbing
- collapse
- apoptotic
- lysis
Fill the topic on physiological apoptosis
5 pathological causes of apoptosis
- cancer
- autoimmune
- neurodegenerative
- viral infections
- atherosclerosis
What does “Physiological” mean?
relates to normal functions and processes in living organisms
What does “pathological” mean?
Pertains to disease or abnormal conditions
Apoptosis and cancer:
Mechanism; In cancer, cells evade _______ allowing them to survive longer leading to unchecked _________ and formation of _________.
- _________ mutations: in many cancers, the tumor suppressor gene ____ that promotes apoptosis in response to DNA damage is mutated. Without this functional gene, damaged cells do not undergo apoptosis leading to tumour progression.
- ________- ___ _________: In certain _________ (eg; follicular ________), the ______ protein that inhibits apoptosis is overexpressed leading to survival of abnormal cells.
apoptosis, growth, tumours
1. p53, p53
2. Bcl-2 overexpression, lymphomas, lymphoma, Bcl-2
Apoptosis and neurodegenerative disease
Mechanism; Excessive apoptosis of ________ leads to neurodegenerative diseases. Neurones are non-_______ cells, so their loss is detrimental.
Examples:
1. Alzeimer’s disease: Abnormal accumulation of __- __________ plaques and tau protein tangles triggers apoptotic pathways in neurons contributing to cognitive decline.
- Parkinson’s disease: The loss of ________ neurons in ______ ________ is linked to increased apoptosis driven by mitochondrial _______ and ________ stress.
neurones, dividing
- Beta - amyloid,
- dopaminergic, substantia nigra, dysfunction, oxidative
autoimmune diseases and immune reactions:
Defective apoptosis of immune cells leads to _____ ________ ________ contributing to autoimmune diseases.
Examples include:
1. _________ ________ __________ (SLE) ; inadequate clearance of apoptotic cells can result in presentation of nucleur antigens to immune system leading to ____________ production.
- Type 1 diabetes: Apoptosis of insulin producing _____ cells in the __________ induced by autoimmune respnses leads to insulin deficiency.
- __________ versus ___________ disease: immune reaction following ______ ________ transplantation; increased apoptosis in skin + GI tract.
self reactive lymphocytes
- systemic lupus erythematosus, autoantibody
- beta, pancreas
- graft, host, bone marrow
Apoptosis and viral infections
Some viruses manipulate the host’s apoptotic machinary to evade the immune system or promote their own replication.
- HIV: HIV infects _______ cells and induces apoptosis in both infected and uninfected cells leading to immune system depletion.
- ______: integrates into host _________ and through expression of vira genes (E6) inhibits ____________ transcription inhibiting apoptosis and promoting malignant transformation.
- T ,
- HPV, genome, p53 ,
What is this a biopsy of?
Apoptosis in a colonic biopsy from a graft versus host disease
Apoptosis results from activation of intracellular proteases called _________.
There are two ways of activation for this; ________ and ________
caspases, extrinsic, intrinsic
Intrinsic pathway of apoptotic activation:
This is _______ pathway such as ________ damage. This is responsible for apoptosis in most situations.
mitochondrial, DNA
Extrinsic pathway of apoptotic activation
- This is a _________ _______ pathway and signals are from outside the cell.
- the Type 1 _______ receptor and _______ and the extrinsic death receptor pathway are important in elimination of self reactive lymphocytes and in killing target cells by __________ ___ cells.
death receptor, TNF, FAS, cytotoxic T
Fill in the differences between apoptosis and necrosis
Fill this table
Autophagy
Start of necrosis
three steps of autophagy
- formation of autophagic vacuole
- fusion of vacuole with lysosomes
- enzymatic digestion of contents
