Cell Injury Flashcards
What is reversible cell injury?
- Cells adapt to changes in the environment
- Once change has gone wrong the cell returns to normal once the stimulus is removed as cells live in a state of equilibrium - many factors can affect this
What is irreversible cell injury?
- Even if factor is removed cannot return back to original state
- Permanent
- Cell death as a consequence
What determines whether cell injury is reversible or irreversible?
- Depends on type, duration and severity of injury
- AND on the susceptibility/adaptability of the cell: nutritional status, metabolic needs (cardiac vs skeletal muscle)
What are the possible causes of cell injury?
- Hypoxia
- Physical agents (radiation)
- Chemicals/drugs
- Infections (bacterial toxins, viruses)
- Immunological reactions
- Nutritional imbalance
- Genetic defects
- Heat and cold
What is hypoxia and what does it cause?
- Deficiency of oxygen
- Causes: anaemia, respiratory failure
- Disrupts oxidative respiratory processes in cell - decreased ATP
- Cells can still release energy via anaerobic mechanisms (only for a limited amount of time)
What is ischaemia and what does it cause?
- Reduction to blood supply to tissue (so reduction in nutrients and oxygen)
- Caused by blockage of arterial supply or venous drainage, e.g. atherosclerosis
- More rapid/severe damage than hypoxia - anaerobic energy release will also stop
What are examples of physical agents and what do they cause?
- Mechanical trauma: affects structure and cell membranes
- Extremes of temperature: affect proteins, chemical reactions
- Ionising radiation: causes DNA damage
- Electric shock - burns
What are examples of infectious agents and what do they cause?
- Bacteria
- Viruses
- Fungi
- Parasites
- Prions
All associated with inflammation and produce various degrees of injury by different mechanisms
What are examples of chemicals and drugs and what do they do?
- Simple chemical (glucose), in excess cause osmotic disturbance
- Poisons (cyanide blocks oxidative phosphorylation), environmental (insecticides)
- Occupational hazards (asbestos) causes inflammation in the lungs
- Alcohol, smoking and recreational drugs
- Causes disruption of cell membranes and proteins
What are examples of immunological reactions and what do they cause?
- Anaphylaxis (type 1 hypersensitivity, IgE mediated)
- Auto-immune reactions (type 2, antibodies directed towards host antigens, type 3 - antigen-antibody complexes)
- Cause damage as a result of inflammation (complement, clotting, neutrophil products etc)
What are the 4 different types of hypersensitivity reaction?
Type 1 - Anaphylaxis - severe reaction - swelling of the face and lips
Type 2 - Basis behind autoimmunity - treats self-cells as if they were something foreign
Type 3 - Antigen/antibody complex - can cause damage
Type 4 - cell mediated
All of these will bring about damage to the cell
What are the specific and generalised conditions cause by an inadequate intake of nutrients?
Specific - Scurvy, Rickets
Generalised - anorexia
What are the specific and generalised conditions caused by an excessive intake of nutrients?
Specific - Hypervitaminosis A/D
Generalized - Obesity
What are examples of genetic defects and what do they cause?
- Sickle cell anaemia (haemoglobin chain)
- Inborn error of metabolism (lack of enzyme causes build up of enzyme substrate)
- Also more subtle variations in genetic makeup determine susceptibility to cell injury from all of the pervious causes
- Cancer
What happens to cells during mechanisms of reversible injury?
Disruption to:
- Aerobic respiration/ ATP synthesis (mitochondrial damage)
- Plasma membrane integrity
- Enzyme and structural protein synthesis
- DNA maintenance
- Some affects ion channels
What is the morphology of the cell during the mechanism of reversible injury?
- Cloudy swelling
- Fatty change
What is the morphology of cloudy swelling in cells and what causes this?
- Mainly due to hypoxia
- Cells are incapable of maintaining ionic and fluid homeostasis
- Failure of energy dependent ion pumps in the cell membrane due to loss of ATP –> energy dependent Na pump leads to influx of Na and water
- There is a build up of intracellular metabolites
What is the morphology of fatty change in cells and what causes this?
- Accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism so that triglycerides cannot be released from the cell, especially in liver
- Occurs with toxic and hypoxic injury (alcohol abuse, diabetes, obesity)
- Macroscopically liver enlarged and pale
What is the ‘point of no return’?
Does not matter if factor is or isn’t there, cell cannot return back to normal
What is necrosis and what is it usually caused by?
- Cell death
- Usually due to pathology
What is the process of necrosis?
- Intracellular protein denaturation and lysosomal digestion of cell
- Cell membrane is disrupted leading to leakage of cell contents
- Inflammatory response in surrounding tissues
- Cell remains are removed by phagocytosis
- Histopathological changes may take some time to appear
What is a useful histological sign that a cell is necrotic?
The loss of a blue staining nucleus
How can you identify coagulative necrosis
- No proteolysis of the dead cells due to denaturation of enzymes
- Architecture of tissues is preserved for some days
- No nucleus; eosinophilic cells
- Grossly firm in texture
- Cells digested by lysosomes of leukocytes
What is a localised area of coagulative necrosis called?
An infarct
How can you identify liquefactive necrosis?
- Digestion of dead tissues so tissues is in liquid viscous state
- Focal bacterial or fungal infections (abscess)
- Grossly, necrotic material is thick, pale in colour
- CNS necrosis as a result of hypoxia often manifested as liquefactive necrosis
How can you identify caseous necrosis?
- Grossly, friable white appearance
- Mostly seen in TB
- Microscopically; granuloma-fragmented cells and granular debris (mass apoptosis) surrounded by inflammatory cells
What is gangrenous necrosis?
Coagulative necrosis with superimposed bacterial infection - liquefactive necrosis
What is fat necrosis?
Focal areas of fat destruction. Fat cells may be liquefied by activated pancreatic enzymes
What is fibrinoid necrosis?
Special type of necrosis seen in immune reactions in blood vessels
How can you identify fibrinoid necrosis?
- Immune (antigen-antibody) complexes are deposited in artery walls together with fibrin that leaks out of the vessels
- Bright pink and amorphous substance in H&E
What are the possible effects of necrosis?
- Functional depends on organ/tissue
- Inflammation
- Release of cell contents activates inflammation
- Cell remains are then phagocytosed
- Finally the necrotic area is replaced by a scar
- If remains are not removed then calcium salts may be deposited in necrotic tissue
What is apoptosis?
- Genetically programmed cell death
- Orderly elimination of unwanted cells
- Important physiological role
- Can occur in pathological situations
- Requires energy
- Distinct pathways involved
- Does NOT cause inflammation
- Different morphology from necrosis
What are the pathological triggers of apoptosis?
- Hypoxia/ischaemia (protein misfolding)
- Viral infection
- DNA damage - if unrepairable p53 triggers apoptosis
- Caspases are activated enzymes that trigger apoptosis
- Cell contents are degraded by enzymes activated by the cell
What are a few physiological roles of apoptosis?
- Deletion of inflammatory cells after an inflammatory response
- Deletion of self-reactive lymphocytes in the thymus
What can result from too little apoptosis?
Cancer
What can result from too much apoptosis?
Degenerative diseases
What is the morphology of apoptosis?
- Cell shrinkage
- Packaging up of nucleus
- Cell membrane remains intact
- Phagocytosed but no widespread inflammation
What is pyknosis?
Nucleus shrinks; darker staining
What is karyorrhexis?
Nucleus fragments
What is karyolysis?
The blue staining DNA in nucleus is digested by endonucleases and the blue staining fades away
What are examples of excessive normal cellular constituents in the accumulation of abnormal substances in cells?
- Water
- Lipid
- Glycogen
What are examples of abnormal endogenous/exogenous material in the accumulation of abnormal substances in cells?
- Carbon
- Silica
- Metabolites
- Cholesterol
What is atherosclerosis?
Accumulation of cholesterol in macrophages and smooth muscle cells in blood vessel walls
- Also found at sites of haemorrhage and necrosis
What are foam cells?
Macrophages ingested lipid
What is amyloid?
A fibrillar protein material that is deposited as a result of pathologic processes leading to an increased production of these proteins
- Deposited in extracellular location in various tissues and organs
What are the 3 different types of amyloid?
- AL (amyloid light chain) - derived from light chain immunoglobins from plasma cells
- AA (amyloid associated) - Derived from proteins synthesised in the liver
- A-beta - Alzheimer’s disease
What causes amyloid?
Chronic inflammation, multiple myeloma, aging and drug abuse
What is the microscopical appearance of amyloid?
- Pink hyaline appearance
- Difficult to identify with H&E
- Special stain: Congo red (easier to identify)
What 2 types of pathological pigmentation are there?
- Endogenous
- Exogenous
What is endogenous pigmentation?
- Lipofuscin-cellular lipid breakdown products
- Melanin
- Haemosiderin-localised bruising - breakdown of RBC
- Bilirubin
ALL APPEAR BROWN
What is exogenous pigmentation?
- CARBON deposition commonest
- In macrophages in alveoli of lungs
- Black pigment = anthracosis
- Inhaled soot/smoke
- In coal workers can be severe and lead to fibrosis = pneumoconiosis
- Tattoos
- Heavy metal salts e.g. lead
- Pigmentation associated with intravascular drug use
What is pneumoconiosis?
Excessive amounts of carbon deposited in the lungs - clotting up and closing of the alveoli
What is dystrophic pathologic calcification?
- Deposits of calcium phosphate in necrotic tissue. Serum calcium is normal - no relation to level of calcium in the body
What is metastatic pathologic calcification?
- Deposits of calcium salts in normal, vital tissue with raised serum calcium levels
- Often seen in connective tissue of blood vessels
- Can compromise function of tissue
What are the 4 causes of raised serum calcium (hypercalcemia)
- Increased levels of parathyroid hormone (hyperparathyroidism) parathyroid gland tumour
- Destruction of bone tissue - leukaemia, metastasis of bone, immobilization
- Excess vitamin D
- Renal failure - causes secondary hyperparathyroidism
