Flashcards in Pathology 2 - Cell Injury Deck (55)
What are the three phases of apoptosis?
- degradation and phagocytosis
What are caspases?
Enzymes that control and mediate apoptosis and cause cleavage of DNA and proteins of the cytoskeleton
Give some triggers of the intrinsic pathway of apoptosis
- irreparable DNA damage
- withdrawal of growth factors/hormones
How is the intrinsic pathway of apoptosis carried out?
- p53 protein is activated which results in outer mitochondrial membrane becoming leaky
- cytochrome C is released from the mitochondria which causes activation of caspases
How is the extrinsic pathway of apoptosis carried out?
- triggered by cells that are a danger eg tumour or virus-infected cells
- initiated by extracellular signals eg TNF alpha
- TNP alpha is secreted by T killer cells and binds to the cell membrane receptor, resulting in the activation of caspases
How are apoptotic bodies disposed of?
They express proteins on their surface, so they can be recognised by phagocytes which engulf and degrade them
What is the difference between budding and blebbing?
Budding is when small parts of the cell break off in apoptosis. Blebbing is when parts of the cell swell out of a disruption in the cell membrane in necrosis.
What are the five main groups of intracellular accumulations?
1) water and electrolytes
Why is hydropic swelling a particular problem in the brain?
If the brain swells, there is nowhere for the pressure to go
What is steatosis?
A accumulation of triglycerides in cells (often in liver) due to alcohol/diabetes mellitus/obesity/toxins
How do lipids accumulate in cells?
- Cholesterol cannot be broken down and is insoluble so must be eliminated via the liver.
- Excess is stored in cell in vesicles.
- Also accumulates in smooth muscle and macrophages in atherosclerotic plaques.
- Present in macrophages in skin and tendons of people with hereditary hyperlipidaemias
How does alpha-1 antitrypsin deficiency lead to accumulation of proteins in the cells?
- liver produces incorrectly folded alpha-1 antitrypsin protein
- cannot be packaged by ER, accumulates within ER and is not secreted
- in systemic deficiency, proteases act unchecked in the lung resulting in emphysema
Give examples of exogenous pigments which could accumulate in the skin
- carbon, coal, dust or soot (urban air pollutants)
What is haemosiderin?
Iron storage molecule derived from haemoglobin. It is deposited in organs with a systemic overload of iron
What is hereditary haemochromatosis?
Genetically inherited disorder which results in increased intestinal absorption of dietary iron. It is deposited in skin, liver, pancreas, heart and endocrine organs, with symptoms of liver damage, heart dysfunction and multiple endocrine failures.
How is hereditary haemochromatosis treated?
What causes the yellow colour of jaundice?
Accumulation of yellow bilirubin
How is bilirubin usually removed from the body?
It is conjugated in liver and excreted in bile
What are the four mechanisms of intracellular accumulations?
- abnormal metabolism
- alterations in protein folding and transport
- deficiency of critical enzymes
- inability to degrade phagocytosed particles
What is calcification of tissues?
Abnormal deposition of calcium salts within tissues. Can be localised (dystrophic) or generalised (metastatic).
Why does dystrophic calcification occur?
Local change/disturbance favours nucleation of hydroxyapatite crystals
Why does metastatic calcification occur?
Due to hypercalcaemia secondary to disturbances in calcium metabolism
What causes hypercalcaemia?
- increased secretion of parathyroid hormone resulting in bone resorption
- destruction of bone tissue
Give some causes of destruction of bone tissue
- primary tumours of bone marrow
- diffuse skeletal metastases
- Paget's disease of bone