Lecture 2 -- Cellular accumulation

A set of flashcards covering key concepts related to cellular adaptation, degeneration, death, and related topics discussed in the lecture.

What substances can accumulate inside cells?

1. Pigments

• Endogenous

  • Lipofuscin

  • Haemosiderin

  • Melanin (normal pigment)

• Exogenous

  • Carbon / coal dust

  • Tattoo pigments

2. Other normal intracellular substances

• Lipids

• Proteins

• Glycogen

What is lipidosis?

Accumulation of triglycerides in parenchymal cells, especially in the liver

What causes lipidosis?

1. ATP deficiency

   • ↓ lipoprotein (VLDL) synthesis → ↑ triglyceride accumulation

2. Toxic compounds

   • Inhibit fatty acid oxidation (= ↓ breakdown of chylomicron → ↑ triglyceride accumulation)

3. Protein malnutrition

   • ↓ lipoprotein (VLDL) production

4. Diabetes mellitus

   • Without insulin, lipoprotein lipase cannot be activated → Chylomicrons, which contain high level of triglyceride, cannot be broken down

What is the morphology of lipid accumulation?

• Empty, round intracytoplasmic vacuoles

• Lipid droplets push the nucleus to the side

What causes protein accumulation inside cells?

1. Defective protein folding

   • Conformational changes (Alpha helix → Beta helix) → Causes decreased of biological activity and increased toxic activity of protein

2. Excess protein presented to cells

   • Immunoglobulin accumulation in plasma cells → Russell bodies

   • Proteinuria (Holes in glomerulus, causing leakage of protein) → Reabsorption in proximal tubules → Hyaline droplets

What may cause defects in protein folding?

• Aging

• Genetic mutations

• Environmental factors

• Amyloidosis

• Alzheimer's disease

• Spongiform encephalopathies

What is the morphology of protein accumulation?

Eosinophilic (pink) appearance in cells

What causes glycogen accumulation?

• Abnormal glucose or glycogen metabolism

  • Glycogen storage diseases

  • Diabetes mellitus

  • Glucocorticoid hepatopathy
    (glucocorticoids increase glycogen synthesis)

How can we differentiate glycogen from lipids?

1. PAS stain (Periodic Acid–Schiff)

   • Glycogen → PAS positive (Dark pink)

   • Lipids → Not visible with PAS

2. Tension surface of glycogen is much less than lipid → Nucleus should not be displaced in glycogen deposition

What is lipofuscin?

• Polymers of lipid, protein, and phospholipid

• During cell turnover, about 5% of cell components cannot be reused → Once they reach a certain level, they become visible histologically

What is the morphology of lipofuscin?

Yellow-brown pigment in cells

How does carbon pigmentation occur?

Inhalation of carbon/coal dust → Alveolar macrophages phagocytose the particles

What is the morphology of melanin?

Brown black in melanocytes

How is haemosiderin formed?

1. RBC breakdown by macrophages

2. Haemoglobin → Globin + iron + haem

• Globin → Recycled

• Iron → Stored as haemosiderin

• Haem → Converted to bilirubin

What stain identifies haemosiderin?

• Normal → Brown

Perls stain

• Haemosiderin appears blue

How is haem excreted from the body?

• Haem converts to biliverdin → Unconjugated Bilirubin

• Leave the macrophages → Bind with albumin in the circulation

• Liver picks up bilirubin from albumin + add gluconic acid onto unconjugated bilirubin = Conjugated bilirubin

• Conjugated bilirubin enters the intestine via common bile duct

• With bacteria protease, conjugated bilirubin is converted to urobilinogen

• 90% urobilinogen pass out body as faeces + 10% enter the kidney and pass out body through urine

What is jaundice?

Elevated bilirubin levels in blood, causing yellow discoloration of tissues

What are the three main types of jaundice?

1. Pre-hepatic

   • Excessive haemolysis (Bilirubin production > The liver’s ability to conjugate them)

2. Hepatic

   • Liver damage affecting bilirubin metabolism

3. Post-hepatic

   • Bile duct obstruction preventing bilirubin excretion

What is amyloidosis?

• Accumulation of abnormal proteinaceous material (amyloid) deposited between cells in tissues (Extraceullar)

• Amyloid is composed of:

  • Fibril proteins (Extremely strong, highly ordered and organized fibers that can be formed by a large number of proteins and peptides)

  • P component

  • Other glycoproteins

What are the four main types of amyloid?

1. AA amyloid

   • Derived from Serum Amyloid A (Positive acute phase protein produced during inflammation by liver)

   • Often associated with chronic inflammation

2. AL amyloid

   • Derived from plasma cells

   • Contains immunoglobulin light chains

3. β-amyloid protein

   • Associated with spongiform encephalopathies

4. Islet amyloid polypeptide

   • Deposited in pancreatic islets

What is the morphology of amyloid?

Under H&E staining, amyloid appears as:

• Extracellular

• Eosinophilic

What stain is used to identify amyloid?

Congo red stain

• Amyloid stains red

What are the two types of pathological calcification?

• Dystrophic calcification

  • Occurs in non-viable or dying tissue

  • Normal serum calcium levels

• Metastatic calcification

  • Occurs in normal tissue with hypercalcaemia

  • Hypercalcaemia can be caused by

    • Increased PTH secretion

    • Vitamine D toxication

    • Destruction of bone tissue

    • Renal failure

What is the morphology of minerals, including calcium under H&E staining?

Basophilic (Purple)

What stain is used to identify calcium deposits from minerals?

Von Kossa stain

• Calcium deposits stain black