1. Abnormal Cellular Accumulations Flashcards Preview

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Where do abnormal cellular accumulations come from?

If a cell can't metabolise something, it will remain within the cell. Products can derive from:
- cell's own metabolism
- extracellular space (e.g. Spilled blood)
- outer environment (e.g. Dust)


What are the 5 main groups of intracellular accumulations?

1. Water and electrolytes
2. Lipids (triglycerides and cholesterol)
3. Carbohydrates
4. Proteins
5. Pigments


What is hydropic swelling and why does it occur?

- Accumulation of fluid in cells.
- Occurs when energy supplies are cut off (eg hypoxia) - Na+ and water influx.
- Indicates severe cellular distress.


Where is hydropic swelling a particular problem, and why?

Brain (cerebral oedema) as swelling presses it against skull and compromises blood supply.


What is steatosis, where and why does this occur?

- Accumulation of triglycerides (lipids).
- Often seen in liver (major organ of fat metabolism).
- Causes:
1. Alcohol (reversible in ~10 days)
2. Diabetes mellitus
3. Obesity
4. Toxins (e.g. Carbon tetrachloride)


Why would cholesterol accumulate in cells and where does it often accumulate?

- Cannot be broken down and is insoluble - can only be eliminated through the liver (so accumulated if liver is compromised). Excess stored in cellular vesicles.

- Accumulates in smooth muscle cells and macrophages in atherosclerotic plaques = foam cells.


What are xanthomas?

Hereditary hyperlipidaemias - accumulation of cholesterol in macrophages of skin and tendons.


What are Mallory's hyaline and when do these occur?

- Damaged keratin filaments.
- Alcoholic liver disease.


What is alpha1-antitrypsin deficiency?

- Liver produces incorrectly folded alpha1-antitrypsin protein.
- Cannot be packaged by ER - accumulates and is not secreted. Causes liver fibrosis and cirrhosis.
- Systemic deficiency: proteases in lung act unchecked resulting in emphysema.


Give an example of the accumulation of exogenous pigments in cells. What are the consequences?

- Air pollutants (carbon/coal dust/soot) inhaled and phagocytosed by alveolar macrophages.
- Causes anthracosis and blackened peribronchial lymph nodes.
- Usually harmless unless in large amounts - fibrosis and emphysema (coal worker's pneumoconiosis)

- Tattooing: pigments phagocytosed by macrophages in dermis and remain there. Some pigments will reach draining lymph nodes.


Why do bruises form after trauma?

Leakage of blood causes local excess of iron - accumulation of haemosiderin.


What is haemosiderin?

Iron storage molecule derived from haemoglobin (yellow/brown).


What is haemosiderosis? When does this occur?

Deposition of haemosiderin in many organs due to systemic iron overload.

Seen in haemolytic anaemias, blood transfusions and hereditary haemochromatosis.


What is hereditary haemochromatosis?

- Genetically inherited disorder resulting in increased intestinal absorption of dietary iron.
- Iron is deposited in skin, liver, pancreas heart and endocrine organs - often associated with scarring in liver (cirrhosis) and pancreas (can cause pancreatic insufficiency).


What are the symptoms of hereditary haemochromatosis?

Liver damage, heart dysfunction and multiple endocrine failures (esp of pancreas).
'Bronze diabetes' as causes tanning and pancreatic destruction.


What is the treatment for hereditary haemochromatosis?

Repeated bleeding


What causes jaundice? What is this product?

- Accumulation of bilirubin.
- Breakdown product of heme (stacks of broken porphyrin rings). Formed in all cells of body (cytochromes contain heme).


How is bilirubin normally eliminated?

Transported from tissues to liver by albumin, and excreted in bile.


Why does jaundice occur?

If bile flow is obstructed or overwhelmed, blood levels of bilirubin rise (accumulate in tissues extracellularly or in macrophages) and cause jaundice.


What are the 4 mechanisms of intracellular accumulation?

1. Abnormal metabolism (e.g. Fatty liver)
2. Alterations in protein folding and transport (e.g. Alpha1-antitrypsin)
3. Deficiency of critical enzymes (e.g. Lysosomal storage disease)
4. Inability to degrade phagocytosed particles


What is tissue calcification and what are the 2 types?

- Abnormal deposition of calcium salts within tissues.

1. Dystrophic = localised. More common, occurs in dying tissue, atherosclerotic plaques, aging or damaged heart valves, tuberculous lymph nodes, some malignancies.

2. Metastatic = generalised.


Why does dystrophic calcification occur?

Local change/disturbance favours nucleation of hydroxyapatite crystals (e.g. Cavities in TB lungs). Does not involve abnormality in calcium metabolism.


Why does metastatic calcification occur?

Due to hypercalcaemia secondary to disturbances in calcium metabolism - hydroxyapatite crystals are deposited in normal tissues throughout the body (usually asymptomatic but can be lethal).


What causes hypercalcaemia?

1. Increased secretion of parathyroid hormone (PTH) resulting in bone resorption:
- primary - due to parathyroid hyperplasia or tumour
- secondary - due to renal failure and phosphate retention
- ectopic - secretion of PTH-related protein by malignant tumours (eg. Lung carcinoma)

2. Destruction of bone tissue:
- primary tumours of bone marrow (e.g. Leukaemia, multiple myeloma)
- diffuse skeletal metastases
- Paget's disease of bone - accelerated bone turnover
- immobilisation