Cell Injury And Death 2 Flashcards
Apoptosis charcateristics
Programmed cell death
Shrinkage
Regulated intracellular program (activates enzymes that degrade DNA and proteins)
DNA breakdown (cleavage, non random)
Apoptosis steps
Condensation
Fragmentation
Apoptic bodies
Physiological apoptosis
Maintain steady state
Hormone controlled
Embryogenesis - develop hands structure by cell death in webbed section
Pathological apoptosis
Cytotoxic T cell
Virus infected/neoplastic
Damaged with damaged DNA (very pink)
Stages of apoptosis
Initiation - intrinsic/extrinsic pathway
Execution - cleave DNA and compartmentalise
Degradation (phagocytosis)
appear eosinphillic
Intrinsic pathway apoptosis
Signal comes from within cell
Triggers:
- DNA damage
- Withdrawal of growth factors/hormones
P53 protein activated = leaky Mitochondrial membrane
Cytochrome C released - activates CASPASES
Extrinsic pathway apoptosis
Extracellular signals Triggers: - tumour cells, virus infected cells TNFa - tumour necrosis factor alpha - binds to cell membrane (death receptor) Activates CASPASES
What do intrinsic and extrinsic pathways result in
Shrinkage
Formation of apototic bodies
Antigens recognised by phagocytes
Ingested and degraded
Apoptosis vs Necrosis/oncosis
Apoptosis
- single cells
- Shrinkage
- nucleus fragmentation into clumps
- intact plasma membrane & cellular contents
- no inflammation
- eliminate unwanted cells
Oncosis/Necrosis
- groups of cells
- swelling
- pyknosis, karryorrhexis, karyolysis of nucleus
- enzymatic digestion, cell leaks out of cell
- membrane disrupted
- INFLAMMATION
- pathological
Gangrene (wet/gas and dry)
Necrosis visible to naked eye
Wet - infection, liquefactive
Dry - exposure to air, coagulative
Gas - infected with anaerobic bacteria (crash/crush injury, bubbles of bacteria)
Infarction
Necrosis caused by reduction in arterial blood flow
-can result in gangrene
Infarct
Area of necrotic tissue
Loss of arterial blood supply
Causes of infarction and where
Reduction of arterial blood supply
- atherosclerosis
- occlusion (thrombus/thromboembolism)
- twisting (testes/bowel)
- compression
Heart, lungs, brain, kidneys, limbs, GI, testes
Types of infarct
White (usually Coagulative) - solid organs
Red (usually Liquefactive) - cerebral
White infarct
Solid organs - heart, spleen, kidney
Occlusion of end artery
Wedge shaped
Coagulative
Red infarct
Haemorrhagic
Loose tissue - lung/bowel
Dual blood supply
Re-perfusion
Complications of infarction
None
Death
Depends on:
- alternative blood supply
- speed (could another route be made)
- tissue involved
- oxygen content of blood (if already anaemic = BAD)
Ischaemia-reperfusion injury
If blood flow is returned to damaged (not yet necrotic) tissue, damage sustained can be worse
- production of free radicals
- lots of neutrophils = more inflammation and more tissue injury
- complement proteins activate complement pathway
Abnormal cellular accumulations examples
caused by: Deranged metabolism Examples: Normal cell components Abnormal cell components: - endogenous from dysfunctional metabolism/synthesis - exogenous (infections/minerals) Pigment
Why can cellular accumulations occur
Abnormal metabolism
Alterations in protein folding and trasnport
Deficient in critical enzymes
Inability to degrade/phagocytoses particles
Accumulation of water - oncosis
Cellular distress eg hypoxia
Sodium and water enter cell
Droplets
Hydropic swellings
Brain - sulci (grooves) not visible, gyri (raised ridges) enlarged
Fatty liver/steatosis
Macrovesicular - large lipid droplets
Microvesicular - within hepatocytes
Cholesterol accumulation
Insoluble
Eliminated via liver
Stored in vesicles
LDL- R abnormality
=
- atheroslclerosis (LDL oxidised, engulfed by macrophages, foam cells —> plaque)
- Xanthoma - cholesterol macrophages within tendons
- Inflammation and necrosis
- cholesterolosis - cholesterol macrophages in gall badder
Accumulation of proteins
Eosinophilic in cytoplasm
Extracellular space sometimes (amyloidosis)
Diseases:
- alcoholic liver disease (mallorys hyaline damaged keratin)
- a1 antitrypsin deficiency
= liver produces incorrect folded a1 antitrypsin protein (protease inhibitor)
Cannot be packaged, accumulates within ER
Proteases in lungs unchecked = emphysema
Accumulation of pigment exogenous
- carbon/soot/dust
Phagocytosed
Black pigment Within lungs (anthracosis) and surface of lungs
Drained into lymph nodes - tattooing
Phagocytosis in dermis
Some pigment reach lymph nodes
Accumulation of pigment endogenous
Haemosiderin - Iron storage - Haemoglobin derived - yellow/brown - local excess = bruise Hereditary haemochromotatosis/haemolytic anaemia
Billirubin - haem broken down Billiverdin —> billirubin (travels bound to albumin) Conjugated in liver and excreted in bile GUT: stercobillingogen = brown faeces BLOOD STREAM: urobillogen = yellow urine
What accumulates as a result of leaky permeable membrane
Potassium
Enzymes
Myoglobin
= local inflammation, general toxic effects, aid diagnosis
Key enzymes leaked
Troponin
AST
CK
Indicate cardiac/liver damage (ALT)
Myoglobin leak
Dead myocardium and striated muscle
Excessive amounts = rhabdomyolysis
Damages kidneys, blocks renal tubes
Renal failure/injury
Pathological accumulation of calcium (localised and generalised)
Localised (dystrophic)
- common
- not to do with calcium metabolism
- atherosclerotic plaques, heart valves, ,malignancy)
Generalised (metastatic)
- due to Hypercalcaemia
- dysfunction in calcium metabolism
Why can metastatic calcification occur
Hypercalcaemia
Increased PTH = increase bone resorption
- primary adenoma/tumour (MOST COMMON)
- secondary renal failure
- tertiary ectopic production (squamous cell lung)
Destruction of bone tissue
- primary tumour of bone marrow
- skeletal metastases
- Paget’s disease - accelerated bone turnover
- Immoblilsation
Hypercalcaemia effects
BONES, STONES, MOANS, GROANS
- bone disease
- renal stones
- confusion/drowsiness
- thirst/Polyuria
- nausea, vomiting, abdominal pain
