Cellular Adaptations and Responses Flashcards
Define humoralism.
Founded by Hippocrates in 400 BC, in which disease or disability results from an imbalance of 4 humors – blood, yellow bile, black bile and phlegm, within the body.
How does disease arise?
Diseases result from molecular or structural alterations to cells and their components:
- Cells normally react to physiological stimuli to maintain homeostasis.
- Altered steady states occur when a physiological stimulus pushes the cell to adapt beyond normal homeostatic range.
- These are pathological stimuli – which stress the cells and cause cellular adaptations that result in altered steady state.
What are the 2 types of cellular adaptation?
Changes in cell growth – size or number
Changes in cell types – differentiation
What types of pathological stimuli can cause adaptive changes?
Altered physiological stimuli, such as altered demands such as an excessive increase or decrease in workload, or a nutritional deficiency.
Chronic irritation – mild physical or chemical injury
What types of stimuli cause cellular injury?
Internal:
- Oxygen depravation
- Nutritional imbalance
- Immune system reactions
- Genetic abnormalities
- Ageing
- Workload imbalance
Environmental:
- Infectious agents
- Physical agents
- Chemicals, drugs and toxins
What may irreversible cell injury cause?
Cell injury is reversible up to a point and depends on if the stimulus is removed or persists.
Irreversible injury > cell death > may lead to pathological calcification of tissues
What 3 cellular alterations in growth can occur as an adaptation?
Atrophy
Hypertrophy
Hyperplasia
What happens in atrophy?
- Cellular or tissue and organ level
- Decreases in size of a cell
- May decrease synthesis of new cellular components or it may increase the degradation of existing cellular components
- If the cell removes or reduces the number of cellular components it has, its functional capacity will also reduce
- A reduction is mass or an organ or tissue due to a decrease in size or number of cells
- Can occur by reduction in cells size, loss of cells or both
Distinguish atrophy and hyperplasia.
Hyperplasia involves developmental failure, with partial failure to develop. Atrophy is a reduction in the mass of a previously normal sized organ or tissue.
What are the causes of atrophy?
Decreased workload – disuse atrophy
Destruction and loss of cells with a lack of replacement
Deprivation of nutrients or growth factors:
- Deficient intake or utilisation of nutrients
- Reduced blood supply to tissues
- Reduced hormone stimulation
- Loss of innervation
Describe what happens to an animal who receives prolonged corticosteroids.
- Prolonged corticosteroid administration has an excessive feedback on the hypothalamic-pituitary axis.
- Reduces the amount of ACTH produced.
- Stimulus of adrenal cortex is reduced and there is atrophy of the adrenal cortex.
- Reduced cortisol production.
- Clinically, suddenly removing corticosteroids, adrenal cortex will not be able to cope and out the animal into severe crisis.
What happens in hyperplasia?
An increase in the number of parenchymal cells in an organ or tissue.
Inappropriate persistent hyperplasia may increase the risk of development of neoplastic disease at that site.
Which cell types can undergo hyperplasia?
Fibroblasts
Lymphocytes
Stratified squamous epithelium
Sweat gland epithelium
Vascular endothelium
What happens in hypertrophy?
Increase in size of a cell due to an increase in the number and size of organelles.
- Can be at cellular or organ and tissue level
- In tissue and organs, there is an increase in the number and volume of a tissue or organ due to parenchymal cell hypertrophy and/or hyperplasia
What are the causes of hypertrophy?
- Increased workload
- Increased hormonal stimulation
- Reactive response to inflammation
- Age related change
What are the 2 types of cell differentiation?
Metaplasia
Dysplasia
What is metaplasia?
Change from the normal cell types to another type that is better able to withstand the insult/stress.
What are the potential problems with metaplasia?
Decreased normal function.
May have an increased risk for developing neoplasia.
What is dysplasia?
A reversible or partially reversible change characterised by disorderly growth.
What is problem with dysplasia?
Highest risk of the development of neoplastic disease.
What are 4 causes of injury?
- Impaired energy/ATP production
- Impaired cell membrane function
- Biological pathway derangement
- Nucleic acid/DNA damage
What causes depletion of energy in cells?
Hypoxia
Mitochondrial damage or dysfunction
What causes hyopxia?
Respiratory failure
Cardiac failure
Reduced vascular perfusion – ischaemia
Anaemia
Severe blood loss
What causes mitochondrial damage or dysfunction?
Damage to mitochondrial membranes
Increased cytosolic calcium (which also interferes with ATP production)
What are the effects of depleted ATP on the cell?
- Sodium potassium ATPase pump fail, sodium is not pumped out of the cell and so increases in intracellular concentration. Water moves in and cell swells.
- Anaerobic metabolism produces lactic acid which can decrease intracellular pH, which affects enzyme activity and metabolic processes.
- Altered protein metabolism (as a result of altered pH), which affects cell function
- Increased cytosolic calcium, as calcium ATPase pumps fail. Activates various intracellular enzymes and cause damage to internal structures, as well as mitochondria, affecting ATP production. Damage to mitochondrial membranes can cause the release of triggers into the cell that cause apoptosis and releasing free radicals.
How do free radicals injure the cell?
- Free radicals can cause lipid peroxidation of membranes.
- Free radical lipid steal electron from the lipid next to it.
- Chain reaction spread throughout membrane.
- Lipids change to peroxides
- Membrane damage
What are the consequences of membrane damage?
- Mitochondrial dysfunction – ATP depletion, triggering of apoptosis
- Plasma membrane dysfunction – loss of osmotic balance, loss of cellular contents and metabolites, influx of fluids
- Leakage of lysosomal enzymes into cytosol – enzymatic digestion of cell components: proteins, nucleic acids, glycogen
What produces free radicals?
Can be generated in physiological processes, such as oxidative phosphorylation, and in pathological processes, such as:
- Inflammation – phagocytes: neutrophils, macrophages
- Metabolism of some drugs/toxins to reactive intermediates
What is reversible cell injury?
An early or mild stage of cell injury when the functional and morphological changes can reverse if the stimulus is removed.
What types of cellular degenerative change can be seen microscopically?
Swelling (hydropic degeneration/change)
Fatty change (lipidosis)
What sort of injuries cause cell swelling?
- Hypoxia – respiratory diseases, circulatory diseases, anaemia.
- Cell membrane injury – free radical attack in lipid peroxidation
- Insertion of transmembrane complexes into the plasma membrane. Membrane attack complex in the complement system and some bacterial toxins do this.
- Cell membrane injury when something inactivates/targets ion channels and pumps. Possible mechanism of some toxins.
Describe fatty changes in lipidosis.
Fatty changes in lipidosis occurs when injuries interfere with lipid metabolism.
- Leads to accumulation of lipid in the cell.
- Most commonly in cells with levels of lipid metabolism, especially hepatocytes.
- Excessive triglyceride accumulation results from excessive delivery and uptake of lipids or reduced metabolism or exportation.
What causes excess delivery of triglycerides?
Excess delivery overwhelms ability to process fatty acids coming in. Caused by excess dietary fat and mobilisation of fat stores, such as in anorexia and metabolic disease.
What causes reduced metabolism of lipids?
Hypoxia
Toxin injury
Deficiency of apoproteins
What causes reduced export of lipids?
Deficiency of apoproteins.
What does lipid accumulation look like histologically?
Appears as vacuoles/clear spaces within cells.
What changes can occur to the liver due to fatty change?
Enlargement of the liver
Changes in texture of the liver (more friable – more likely to crumble and break) due to fat accumulation
Greasy surface sin post-mortem examination of the liver.
What is the significance of hydropic change and fatty change?
- Impaired cell function and potentially to the tissue or organ that they belong to.
- If injury is transient, may permit return to normal structure and function.
- If the cause of injury persists, persistence of degenerative changes with impaired cell function.
- Prolonged or severe injury or degenerative change may progress to irreversible cell injury and cell death.
What are the 2 main processes that cell death occurs by?
Apoptosis – regulated mechanism/ programmed cell death. Single cells affected. Avoids stimulating inflammation.
Necrosis – unregulated mechanism. Multiple cells affected. Stimulates inflammation.
What changes does necrosis make to the cell?
Cytoplasmic changes – increased cytoplasmic eosinophilia deeper pink/red cytoplasm
Nuclear changes:
- Karyolysis – nuclear fading/dissolution of nucleus in enzymatic degradation
- Pyknosis – nuclear condensation by clumping of chromatin
- Karyorrhexis – nuclear fragmentation
What do the types/patterns of necrosis depends on?
- The cell and tissue type
- The cause of the necrosis
- Involvement of other factors such as secondary infection
Name 5 types of necrosis.
Coagulative necrosis – most common. Causes include hypoxia/ischaemia (reduced tissue perfusion) and toxins
Gangrene
Fat necrosis
Caseous necrosis
Liquefactive necrosis
Describe dry gangrene.
- Limb extremities, ears, tail or udder
- Coagulative necrosis caused by ischaemic injury
- Followed by dehydration of the necrotic tissue in mummification
- Dry gangrene caused by ergot toxicity
Describe wet gangrene.
- Necrosis of tissues followed by invasion and liquefaction by saprophytic bacteria from the environment
- Gangrenous mastitis – necrosis and bacteria putrefaction
What is fat necrosis?
Necrosis of adipose tissue
What is caseous necrosis?
Caused by different infections of the body
What is liquefaction necrosis?
- Occurs in the CNS, often as a result of hypoxia-ischaemic injury.
- The necrotic tissue is digested and forms a semi-liquid.
- Softening of CNS tissue is called malacia.
- In other tissues it is associated with pus-forming (pyogenic) organisms.
When is pus formed?
- Can from when pyogenic organisms, such as some bacteria, attract many neutrophils into the site of infection.
- The neutrophils attack the bacteria.
- The neutrophils die and release lysosome enzymes that liquify the cells and surrounding necrotic tissue.
- This is pus.
- Sometimes the bacteria survive and the process continues.
Name and describe the 2 different mechanisms of pathological calcification of tissues.
Dystrophic calcification – can occur at sites of necrosis.
Metastatic calcification – associated with disturbed calcium metabolism resulting in hypercalcaemia and deposition of calcium salts in tissue.
What are the possible causes of hypercalcaemia?
- Conditions causing excessive parathyroid hormone production by the parathyroid glands
- Production of parathyroid hormone related peptide by other tissues, which occurs in some tumours
- Chronic kidney disease
- Vitamin D/poisoning with some rodenticides
Which tissues can calcification arise in?
Stomach mucosa
Lungs, pleura
Blood vessel walls
Endocardium
What is jaundice/icterus?
Excess accumulation of bilirubin in the blood and extracellular tissue fluids.
What is prehepatic/haemolytic icterus?
Excessive bilirubin production due to haemolysis.
What is hepatic icterus?
Caused by hepatocyte damage and decreased metabolism of bilirubin.
What is posthepatic/obstructive icterus?
Obstruction of bile excretion, for example, a tumour.
What is amyloidosis and amyloid deposition?
These are disorders are associated with extracellular deposition of proteins preferred to as amyloid.
Most commonly caused by chronic inflammation/infection. Less commonly associated with plasma cell disorders.
Amyloid deposition may be localised to a particular site/tissue. Or systemic where multiple tissues/sites can be affected. This may cause organ dysfunction.
What are the 5 main general pathological processes?
- Generation including cell death
- Altered growth or differentiation (non-neoplastic) (congenital or acquired)
- Inflammation and healing
- Blood flow and circulatory changes
- Neoplasia
List 5 cellular pathological changes affecting hepatocytes that might account for the changed colour of a liver.
Hepatocellular vacuolar change with water accumulation = hydropic chnage
Hepatocellular vacuolar change with lipid accumulation = fatty change
Hepatocellular vacuolar change with glycogen accumulation
Hepatcocellular necrosis
Amyloidosis and jaundice are extracellular possibilities.
How might a pituitary tumour that autonomously produces excess ACTH cause hyperadrenocorticism?
Excess stimulation of the adrenal cortical cells to produce cortisol in both adrenal glands. Bilateral hypertrophy of the adrenal cortex causes bilateral adrenal enlargement.
How might an adrenal cortical tumour that autonomously produces excess cortisol cause hyperadrenocorticism?
Excess cortisol production by the tumour (not under normal regulatory control). Negative feedback on pituitary suppresses ACTH production. Loss of ACTH stimulus of both adrenal glands results in bilateral cortical atrophy/reduced mass. But the tumour within the adrenal gland may make this gland appear enlarged.
How might prolonged corticosteroid treatment cause hyperadrenocorticism?
Corticosteroids suppresses ACTH production by the pituitary via negative feedback. Loss of ACTH stimulus of both adrenal glands results in bilateral cortical atrophy/reduced mass.
