1. Abnormal Cellular Accumulations

Question 1

Where do abnormal cellular accumulations come from?

Answer 1

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)

Question 2

What are the 5 main groups of intracellular accumulations?

Answer 2

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

Question 3

What is hydropic swelling and why does it occur?

Answer 3

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

Question 4

Where is hydropic swelling a particular problem, and why?

Answer 4

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

Question 5

What is steatosis, where and why does this occur?

Answer 5

• 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)

Question 6

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

Answer 6

• 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.

Question 7

What are xanthomas?

Answer 7

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

Question 8

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

Answer 8

• Damaged keratin filaments.

- Alcoholic liver disease.

Question 9

What is alpha1-antitrypsin deficiency?

Answer 9

• 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.

Question 10

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

Answer 10

• 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.

Question 11

Why do bruises form after trauma?

Answer 11

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

Question 12

What is haemosiderin?

Answer 12

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

Question 13

What is haemosiderosis? When does this occur?

Answer 13

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

Seen in haemolytic anaemias, blood transfusions and hereditary haemochromatosis.

Question 14

What is hereditary haemochromatosis?

Answer 14

• 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).

Question 15

What are the symptoms of hereditary haemochromatosis?

Answer 15

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

Question 16

What is the treatment for hereditary haemochromatosis?

Answer 16

Repeated bleeding

Question 17

What causes jaundice? What is this product?

Answer 17

• Accumulation of bilirubin.

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

Question 18

How is bilirubin normally eliminated?

Answer 18

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

Question 19

Why does jaundice occur?

Answer 19

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

Question 20

What are the 4 mechanisms of intracellular accumulation?

Answer 20

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

Question 21

What is tissue calcification and what are the 2 types?

Answer 21

• 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.

Question 22

Why does dystrophic calcification occur?

Answer 22

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

Question 23

Why does metastatic calcification occur?

Answer 23

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).

Question 24

What causes hypercalcaemia?

Answer 24

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