Pathology - cells (including cell death) Flashcards
Define autophagy
process for cells to remove organelles + denatures proteins
Define heterophagy
process of cell consuming material from its environment
Where is energy generated in a cell and what happens if this is damaged?
Mitochondria - ATP produced in intermembrane space by oxidative phosphorylation
Mitochondria also regulate programmed cell death (apoptosis)
If mitochondria damaged by toxins, decreased blood supply or trauma - ATP generation fails - cell dies by necrosis
What forms of mitochondrial disease are there?
X-linked = fathers cannot pass to sons Autosomal = caused by autosomal gene abnormality Maternally-inherited = mutation in mitochondrial DNA
What are growth factors?
- promote entry of cells into cell cycle
- remove block on cell cycle progression
- prevent programmed cell death (apoptosis)
- enhance synthesis of cell components (eg epiderm growth factor for skin wound healing)
Describe the cell cycle
G1 = cell preparing to divide - cell grows + copies organelles
S-phase (in interphase) = DNA replicated
G2 = cell continues to grow, centrosome replication completed
M-phase = mitotic phase = cell divides its copied DNA + cytoplasm to make 2 new cells (involves mitosis + cytokinesis)
Describe stem cells
- have capacity for self-renewal
- asymmetric division (one daughter cell can mature while other remains stem cell)
Totipotent stem cell
- embryonic
- can give rise to all types of differentiated/mature tissues
Adult/tissue stem cells
can only replace cells in tissues in which they reside
Multipotent stem cells
- in bone marrow + fat
- can give rise to cartiocytes (cartilage cells), osteocytes, adepocytes (fat cells) + myocytes (muscle cells)
What are 4 cell adaptations
Hypertrophy Hyperplasia Atrophy Metaplasia (reversible changes in size, number, phenotype, metabolic activity or functions of cells in response to changes in their environment)
Hypertrophy
- increase in size of cells (increase in size of affected organ)
- physiological or pathological
- related to increased workload
physiological = uterus in pregnancy
pathological = myocardium in hypertension
Hyperplasia
- increase in number of cells in organ/tissue in response to a stimulus
- can only occur if cells can divide
- can be physiological or pathological
- can occur alongside hypertrophy
- regresses if stimulus removed
Atrophy
- decrease in size of organ/tissue due to decreases cell size + number
- physiological or pathological
eg disuse atrophy, denervation atrophy, pressure atrophy, inadequate nutrition
Metaplasia
- reversible change in which one differentiated cell type is replaced by another cell type
- adaptive response - replacement cell type better able to withstand adverse environment
- caused by reprogramming of stem cells
What is necrosis?
- accidental/unregulated cell death
- always pathological
- damage to cell membranes - lysosomal enzyme digestion of cell
- leakage of cell contents - inflammatory reaction
Mechanisms underlying necrosis
- depletion of ATP
- mitochondrial damage
- influx of calcium
- accumulation of oxygen-derived free radicals
- membrane permeability defects
- DNA + protein damage
What is apoptosis?
- programmed cell death
- no inflammatory reaction
- many normal functions
- physiological (eg destruction of cells during embryogenesis) + pathological (eg viral infections)
What are the 2 types of pathological calcification?
dystrophic = normal serum calcium, calcium deposited in dead/damaged tissue Metastatic = hypercalcemia, increased PTH, increased bone turnover, vitamin D excess, sarcoidosis
How are apoptotic cells removed?
- phosphatidylserine flips from inner to outer aspect of cell membrane
- recognised by macrophage receptors
- apoptotic cells secrete soluble factors which recruit macrophages
- apoptotic bodies get coated with thrombospondin or C1q which attracts macrophages
- dead cells disappear within minutes
