2 - Cell Injury Flashcards
What happens to cells when their homeostasis is interrupted by injury
Cellular adaptation (reversible) –> Cellular Injury –> Death
What things can cause cell injury?
1. Hypoxia
2. Toxins
3. Radiation
4. Microorganisms
5. Immune mechanisms (hypersensitivity and autoimmune)
6. Dietary insufficiency and excess
7. Physical agents (temp, pressure, electric currents, direct trauma)
What are the different casues of hypoxia?
1. Ischaemic - interruption to blood supply, enough o2 in blood but cannot perfuse
2. Anaemic - Decreased ability of Hb to carry O2, e.g CO poisoning and anaemia
3. Hypoxaemic - Arterial content of oxygen is low, e.g high altitudes and secondary to lung disease
4. Histotoxic - Inability to utilise oxygen in cells due to disabled oxi phos, e.g CN poisoning
What is the tolerance of hypoxia in different tissues?
What cell components are most susceptible to injury?
Summarise hypoxic cell injury.
What is an ischemia repurfusion injury?
When blood supply is returned to ischaemic tissue that is not necrotic sometimes injury is worse than if not restored
- Increase production of oxygen free radicals
- Increased number of neutrophils with blood supply so more inflammation
- Delivery of complement proteins and activation of complement pathway so more inflammation and cell membrane damage
What is haemachromatosis and Wilson’s disease?
H = Excess iron
W = Excess copper
Leads to unbound metals in the body that can form free radicals via Fenton reaction
How does the body control free radicals?
- Antioxidant scavengers (vitamin A,C and E)
- Metal carrier and storage proteins for Fe and Cu (transferrin)
- Enzymes, e.g superoxide mutase, GSH, catalase
What are heat shock proteins?
Protection by cell against effects of injury. Trauma leads to more synthesis of heat shock proteins, e.g ubiquitin. Try to mend misfolded proteins
What do injured cells look like with light microscopy?
- Cytoplasm changes
- Nuclear canges
- Abnormal cell accumulations
What happens to the nucleus of cells that die from oncosis?
- Pyknosis (shrinkage)
- Karyorrhexis (fragmentation)
- Karyolysis
What do reversibly injured cells look like under the electron microscope?
- Swelling of cell and organelles as no Na/K pump
- Blebs
- Detachment of ribosomes from ER
- Clumped chromatin due to lowered pH
What do irreversibly injured cells look like under an electron microscop?
Same as reversible injury plus:
- Myelin figures (damaged membranes)
- Lysis of ER
- Large densities in mitochondria
- Nuclear changes
How can you diagnose cell death looking at EM microscope?
Dye exclusion therapy, those that don’t take up the dye are still alive as they have good membrane integrity
What is
- oncosis?
- necrosis?
- apoptosis?
Oncosis - Cell death with swelling, spectrum of changes that occur prior to cell death in cells injured by hypoxia
Necrosis - In a living organism, the morphological changes that occur some time after death. It is an appearance, not a type of cell death
Apoptosis - Cell death with shrinkage. Induced by intracellular program that activates enzymes that degrade itself
What are the different types of necrosis?
Main:
- Liquefactive (colliquitive)
- Coagulative
Special:
- Fat
- Caseous
Why are there two main types of necrosis?
What does coagulative necrosis look like under the microscope?
- Solid clump of dead tissue
- Ghost outline of cells
Accute inflammatory response
PROTEIN DENATURATION GREATER THAN PROTEIN DEGRADATION
What does liquefactive necrosis look like?
- Lots of dead neutrophils
- Degradation greater than denaturation
- No clear visible structure
What does caseous necrosis look like?
- Amorphus debris
- Associated with infections like TB
- Cheese like
What does fat necrosis look like?
- Release of free FA that react with calcium forming chalky deposit. Mostly seen in pancreatitis as lipases are released that will break down adipose tissue in pancreas
- Can occur in breast due to trauma and can be misdiagnosed as breast cancer by patient
What is gangrene, and what does it mean to be wet, dry and gas?
Gangrene = Necrosis visible to naked eye
Dry = necrosis modified by exposure to air and drying, coagulative
Wet = necrosis modified by infection, liquefactive
Gas = wet gangrene with anaerobic bacteria that produce palpable bubbles of gas
What is an infarction and an infarct?
Infarction = necrosis caused by reduction in arterial blood flow, can lead to gangrene. Cause of necrosis
Infarct = area of necrotic tissue due to loss of arterial blood supply. Ischemic necrosis. Lesion due to infarction
Why are some infarcts white?
- Mainly in solid organs that have good stromal support
- Occlusion of end artery that is sole source of blood
- Little haemorrhage from adjacent tissue, death of all downstream tissue
- Heart, spleen and kidney, wedge shaped
Why are some infarcts red?
- Mainly in loose tissue, poor stromal support allowing bleeding
- Mainly due to dual blood supply, e.g lung
- Not enough blood for reperfusion and save with dual blood supply but bleeds onto dead tissue
- Can be due to reperfusion, e.g after stroke, in area too far gone
What is tumour lysis syndrome?
Complication with cancer treatment where a lot of cancer cells lyse at once and release large amounts of toxic molecules, e.g increase in K levels quickly
What does apoptosis look like under the microscope?
What does accumulated cholesterol look like under the microscope?
Cholesterol clefts, needle spaces
What is the process of apoptosis?
Initiation: intrinsic or extrinsic that activates caspases that cleave DNA and proteins of cytoskeleton
Execution
Degradation and Phagocytosis: Apoptic bodies express proteins on surface so recognised by phagocytes
How is the intrinsic pathway of apoptosis carried out?
- Integrating signal comes from within the cell, e.g DNA damage, removal of growth hormone.
- P53 protein is activated and this results in mitochondrial membrane being leaky
- cytochrome C is released from mitochondria, activating caspases
How is the extrinsic process of apoptosis carried out?
- Initiated by extracellular signals.
- One signal is TNFalpha released by T killer cells.
- Binds to death receptor on cell membrane, activating caspases and downstream degradation
What are the differences between apoptosis and oncosis?
- Budding in apoptosis but blebbing in oncosis
- Inflammation in oncosis but not in apoptosis
When does fluid accumulate in cells?
Hydropic swelling when energy supplies cut off. Na floods into cell and so does water. Can cause coning in brain
When do lipids accumulate in cells? (steatosis)
In liver
- Alcohol
- Diabetes Mellitus
- Obesity
- Toxins
What do accumulated proteins look like?
Eosinophilic droplets or aggregations in cytoplasm.
When do exogenous pigments accumulate in cells?
Carbon/Coal Dust/Soot: phagocytosed by macrophages leading to anthracosis and blackened peribronchial lymph nodes. Harmless till leads to fibrosis and pneumoconiosis
Tattoos: phagocytosed in dermis and left there
What is haemosiderosis?
- Haemosiderin stores iron in cells and is brown as derived from Hb
- Forms when local excess of iron e.g bruise
- When systemic overload of iron, haemosiderin deposited in lots of organs
- Seen in haemolytic anaemia, hereditary haemochromatosis and blood transfusions
NO TISSUE DAMAGE
What does jaundice look like and what is it caused by?
- Accumulation of bilirubin, bright yellow
- If bile flow is obstructed or overwhelmed, bilirubin in blood rises and jaundice results
- Deposited in tissues extracellularly or in macrophages
Why does dystrophic calcification occur?
- Localised, more common in area of dying tissue, aging heart valves, atherosclerotic plaques, tuberculus lymph nodes and malignancies
- No abnormality in metabolism or serum calcium concentrations. Local change favours nucleation of hydroxyapatite crystals
What causes hypercalcaemia?
- Increase secretion of PTH
- Destruction of bone tissue
