Apoptosis, cellular accumulations and metabolic derangements
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What is apoptosis?
Apoptosis is programmed cell death. It is a highly coordinated sequence of events that requires energy.
What is the difference between physiological and pathological apoptosis?
Physiological apoptosis is the involution of tissues during embryonic development or age related involution/atrophy of the thymus. Whereas pathological apoptosis is irreversible cell injury with different underlying causes including infectious agents, ionising radiation and chemicals
Compare the steps in apoptosis with necrosis
- 1. Chromatin condenses
- 2. DNA fragments
- 3. Cytoplasm shrinks and membrane blebs
- 4. The phospholipid phosphatidylserine is exposed on the cell surface
- 6. Receptors on phagocytic cells (macrophages) then engulf the cell fragments
- 1. Chromatin clumps
- 2. Mitochondria swell and rupture
- 3. Plasma membrane ruptures
- 4. This affects neighbouring cells
- 5. Stimulates inflammatory response
What does apoptosis look like under the microscope compared to necrosis?
Where cells are undergoing apoptosis you can see a clear line around them (as they have shrunk) and can also see apoptotic bodies. Where there is necrosis there is no clear cell outlines, varying nuclear changes and a eosinophilic. homogeneous cytoplasm.
What are some examples of intracellular accumulations that are normal cellular components?
Water, lipids, proteins, carbohydrates
What are some examples of intracellular accumulations that are abnormal exogenous substances?
Minerals or products of infectious agents
What are some examples of intracellular accumulations that are abnormal endogenous substances?
Products or abnormal synthesis or metabolism
What are some examples of extracellular accumulations?
What are the causes of intracellular accumulations?
- Decreased rate of metabolism - leads to build up of normal endogenous substances e.g. build up of triglycerides leads to fatty change in the liver
- Genetic or acquired defects in metabolism, packaging, transport or secretion e.g. lysosomal storage diseases
- Failure of enzymatic machinery to degrade or transport an abnormal exogenous substance
What is lipofuscin? When does it occur?
Lipofuscin is the accumulation of the final undegradable remnants of autophagocytosis (the indigestible parts of damaged cells that accumulate within lysosomes). It occurs with age.
What colour does lipofuscin make muscle turn?
What does amyloid look like histologically?
Eosinophilic, amorphous and hyaline substance
Why is amyloidosis a problem?
Amyloid compresses tissue cells causing cell atrophy or death
What is secondary amyloidosis? When does secondary amyloidosis occur?
Secondary amyloidosis is the excessive or prolonged production of acute phase proteins by the liver. It occurs secondary to chronic inflammation.
Where does secondary amyloidosis commonly occur?
In the kidney, also the liver, pancreas, GIT and blood vessels
What is pathologic calcification?
When calcium salts are deposited in dead, dying or normal tissues
What is the difference between dystrophic and metastatic calcification?
Dystrophic calcification takes place in dead/necrotic tissues, whereas metastatic calcification takes place in animals with hypercalcaemia
What happens during dystrophic calcification?
Dead/dying cells cannot regulate their cytoplasmic calcium influx so calcium accumulates in the mitochondria
What are the most common causes of metastatic calcification?
- Renal failure - if you are retaining phosphates due to renal failure then your phosphate/calcium balance is not right. The body thinks it is losing calcium so it trigger the PTH gland to release more. This is secondary renal hyperthyroidism.
- Vitamin D toxicosis - ingestion of calcinogenic plants by herbivores leads to severe soft tissue mineralisation. This mainly involves the aorta, heart and lungs. Acute vitamin D toxicosis in dogs and cats is commonly caused by ingestion of rodenticides containing cholecalciferol.
- PTH hyperparathyroidism - overactive PTH gland
- Destruction of bone from primary or metastatic neoplasms
What is gout? What species are more commonly affected?
Gout is deposits of sodium irate crystals or urates (tophil). Birds, reptiles and humans are prone to gout.
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