Pathology - Cell Injury Flashcards
What is apoptosis and describe the stimuli and features
- programmed cell death, removes unwanted cells and stops excess growth
- cell dies by internal suicide program causing protein breakdown by caspases
- plasma membrane remains intact and does not involve inflammation, cell becomes target for phagocytosis
- 2 phases: initiation phase (intrinsic and extrinsic) and execution phase
features: cells shrink, no inflammation, chromatin condensation, fragmentation, cell blebbing, phagocytosis
stimuli: embryogenesis, hormone dependent involution, DNA damage, developmental atrophy, post inflammation
What happens at the cellular level in apoptosis
cell shrinkage chromatin condensation fragmentation formation of blebs phagocytosis by macrophages
Describe the mechanisms involved in apoptosis
1) Initiation phase
- intrinsic pathway = mitochondrial permeability increased, causes cytochrome c release, activates caspases
- extrinsic pathway = activation of death receptors (TNF family) causing activation of caspases (protease enzymes)
2) Execution phase
- caspases act on cell components causing protein degradation, removal of dead cells by phagocytosis
Describe the cellular changes in necrosis
- cellular swelling, eosinophilia, myelin figures, nuclear changes (pyknosis, karyolysis, karyorrhexis)
- organelle disruption, cell rupture, inflammation
What are the patterns of tissue necrosis
- coagulative: characterised by protein denaturation, architecture preserved, common after MI
- liquefactive: characterised by enzymatic digestion, common after CNS hypoxia
- caseous: exhibits coagulation and liquefaction, seen in Tb
- fat: characterised by lipase activation
- fibrinoid: due to antigen-antibody complex deposition in blood vessel walls
What happens inside cells when they are injured (damage that occurs after severe ischaemia)
- depletion of ATP: causes failure of ion pumps and cell swelling
- mitochondrial damage: causes leaking of cytochrome c leading to apoptosis
- increased intracellular calcium: causes activation of phospholipase which degrades membrane phospholipids
- accumulation of oxygen-derived free radicals: causes damage to DNA and RNA
- defects in membrane permeability: effects intracellular osmolarity and enzyme activity
- damage to DNA and protein: leads to activation of apoptosis
What are the morphological and chemical changes associated with early cell injury
morphological: cell swelling, membrane blebbing, chromatin clumping, ribosomes detach from ER
chemical: depletion of ATP, failure of Na+/K+ATPase, increased intracellular Ca+2, generation of free radicals
What is a free radical and what are their pathologic effects
unstable, partially reduced molecules with unpaired electrons in the outer orbit
causes necrosis or apoptosis
effects: lipid peroxidation, oxidation of proteins, DNA lesions
What are the stages of ischaemic cell injury
reversible: cells swell, membrane blebbing, nuclear chromatin clumping, ribosomes detach from ER
irreversible: nuclear pyknosis/karyolysis/karyorrhexis, lysosome rupture, mitochondrial vacuolization
Describe the sequence of events in reversible ischaemia
- initially reduced oxidative phosphorylation causing reduced ATP production
- failure of Na+/K+ pump, cause increased intracellular Na+ and decreased K+ and cellular swelling
- failure of Ca+2 pump, cause increased intracellular Ca+2 which activates phospholipase (degrades membranes)
features: cellular swelling, membrane blebbing, nuclear chromatin clumping, ribosomes detach from ER
What are the phenomena that characterise irreversible cell injury
inability to reverse mitochondrial dysfunction and development of profound disturbances in membrane function
What are the morphological features of irreversible ischaemia
nuclear destruction
lysosomal rupture
severe mitochondrial vacuolization
death by necrosis or apoptosis
What are some examples of proteins that leak across a degraded cell membrane
cardiac (creatinine kinase and troponin)
bile duct epithelium (alkaline phosphatase)
hepatocytes (transaminases)
Describe reperfusion injury
- increased injury to ischaemic cells with restoration of perfusion
- due to generation of reactive oxygen and nitrogen species and activation of inflammatory/complement cascades
What is atrophy and what are the causes and mechanisms
- decrease in cell size and number, may be physiological or pathological
causes: decreased workload, denervation, reduced blood flow, inadequate nutrition, loss of endocrine stimulation
mechanisms: decreased protein synthesis or increased protein degradation (mainly by ubiquitin-proteasome path)
examples: fracture disuse, damage to nerves causing muscle atrophy, reproductive organs from lack of estrogen
What is hyperplasia and what are the types
increase in the number of cells
physiologic: hormone (breast size in puberty), compensatory (post partial hepatectomy)
pathologic: excess hormone (BPH), viral infection (papillomavirus)
What are the cellular mechanisms of physiological hyperplasia
increased growth factor production
increased growth factor receptors
activation of intracellular signalling
What are the clinical features of BPH
increased frequency, nocturia, difficulty starting and stopping stream, dribbling, dysuria, increased infections
What are some features of diffuse toxic hyperplasia of the thyroid gland (graves disease)
tachycardia, palpitations, heart failure, eye staring, lid lag, proptosis, malabsorption, diarrhoea, tremor, anxiety
What is hypertrophy and what are the types
-increase in the size of a cell due to synthesis of structural components
- physiologic: increase in size of breast during lactation and uterus during pregnancy, skeletal muscle with exercise
- pathologic: heart in chronic hypertension
What is metaplasia and describe the mechanism, some examples and what are possible outcomes
- replacement of one normal cell type with another normal cell type, reversible and may be adaptive or pathological
mechanism: reprogramming of cells involving signals from cytokines, growth factors, genes, ect
examples: squamous to columnar in barrett esophagus, columnar to squamous in smoking (most common)
outcomes: reversibility, ongoing, malignant transformation
What are the 2 different forms of pathological calcification and give an example of each
- Dystrophic calcification = arises in non-viable tissue in presence of normal calcium levels
- example: arteries in atherosclerosis - Metastatic calcification = arises in viable tissue in setting of hypercalcaemia
- example: gastric mucosa, pulmonary calcinosis, nephrocalcinosis
What are the causes of hypercalcaemia (what are the causes of metastatic calcification)
- increased PTH secretion: hyperparathyroidism
- destruction of bone tissue: skeletal metastasis
- vitamin D related disorders: sarcoidosis
- renal failure: secondary hyperparathyroidism
What is steatosis and what are causes of hepatic steatosis
- the abnormal accumulation of TAG within parenchymal cells due to excessive entry or defective metabolism
- can occur in: heart muscle, kidney, liver, skeletal muscle
- cause of hepatic steatosis: alcohol, toxins, protein malnutrition, diabetes, obesity
