1.8 about 20 minDeep Learning viewL1 p.39–40, 46–48

Calcification, accumulations and amyloid

Injured and stressed tissues collect abnormal material. Ask three questions of any deposit: what accumulates, where does it go, and why.

What, where and why

L1 p.8, 40, 46

  • Intracellular accumulation

    What accumulates
    Normal substances in excess (lipid, glycogen), abnormal proteins, pigments
    Where
    Inside cells
    Why
    Overproduction, failure to process or degrade, or uptake of exogenous material

  • Pathologic calcification

    What accumulates
    Calcium salts (with phosphate)
    Where
    In damaged tissue (dystrophic) or normal tissue (metastatic)
    Why
    A local nidus of dead tissue, or high serum calcium or phosphate

  • Amyloid

    What accumulates
    Misfolded proteins in β-pleated sheet fibrils
    Where
    Outside cells
    Why
    Overproduction of a precursor protein or an abnormally folding protein

Intracellular accumulations

L1 p.1, 8

  • Lipid: triglyceride (steatosis)

    Example
    Fatty liver in alcohol use, obesity, diabetes
    Mechanism
    More fat delivered or made than the hepatocyte can package and export

  • Lipid: cholesterol

    Example
    Foam cells in atherosclerotic plaques
    Mechanism
    Macrophages take up oxidized LDL (1.5)

  • Glycogen

    Example
    Hepatocytes and renal tubules in poorly controlled diabetes; glycogen storage diseases
    Mechanism
    Excess substrate or a missing enzyme

  • Protein

    Example
    Reabsorption droplets in proximal tubules with proteinuria
    Mechanism
    Overload of a normal process

  • Lipofuscin

    Example
    Brown granules in aging and atrophic cells (heart, liver, neurons)
    Mechanism
    Undigested residue of lipid peroxidation and autophagy

  • Hemosiderin

    Example
    Iron excess; old hemorrhage
    Mechanism
    Stored iron aggregates

  • Carbon (anthracosis)

    Example
    Lungs and hilar nodes of city dwellers and smokers
    Mechanism
    Inhaled exogenous pigment taken up by macrophages

Dystrophic and metastatic calcification

L1 p.39–40

Dystrophic calcification

  • In dead or damaged tissue
  • Serum calcium normal
  • Lecture example: traumatic fat necrosis of the breast
  • Also: saponified fat in pancreatitis, caseous TB, atheromas, damaged heart valves

Metastatic calcification

  • In normal tissue
  • Serum calcium or phosphate high
  • Lecture example: hyperparathyroidism → nephrocalcinosis
  • Other causes: bone destruction (myeloma, metastases), vitamin D excess, chronic kidney disease. Favoured sites: kidney, lung, gastric mucosa, vessels
L1 p.39–40

Core activity · Almost Twins

Almost Twins

Two look-alikes side by side. Decide what they share, then pick the clue that separates them and say why it works.

Look-alike A

Dystrophic calcification

necrotic fatSerum Ca²⁺ normal
Breast after blunt trauma (schematic).
  • Basophilic calcium deposits in tissue
  • Deposits in dead or damaged tissue; serum calcium normal
  • Fat necrosis, caseous TB, atheromas, damaged valves

Step 1 · What they share

What do they share?

Select every feature that both show.

Amyloid

L1 p.46

Amyloid is misfolded protein that aggregates outside cells. Whatever the precursor, the fibrils share a β-pleated sheet structure and appear on electron microscopy as linear, nonbranching fibrils. On H&E amyloid is an amorphous, eosinophilic, glassy extracellular material. With Congo red it stains salmon-red and shows apple-green birefringence under polarized light, the confirmatory finding.

Teaching schematic

Congo red, ordinary light: salmon-red deposits
Polarized light: apple-green birefringence
Amyloid around a small vessel stained with Congo red, under ordinary and polarized light.L1 p.46

Deposits press on neighbouring cells and stiffen tissues, causing pressure atrophy and organ dysfunction. Amyloidosis is systemic when deposits form in many organs (for example kidney, heart, liver, spleen, nerves) and localized when confined to one organ or tumour.

Amyloid types: precursor to setting

L1 p.47–48

  • AL

    Precursor
    Immunoglobulin light chains (λ more often than κ)
    Setting
    Plasma cell disorders: multiple myeloma, primary amyloidosis
    Typical sites
    Heart, kidney, nerves, tongue

  • AA

    Precursor
    Serum amyloid A, an acute-phase protein from the liver
    Setting
    Chronic inflammation: rheumatoid arthritis (most common), ankylosing spondylitis, Crohn disease, ulcerative colitis, chronic infections; familial Mediterranean fever
    Typical sites
    Kidney, liver, spleen

  • Aβ₂M

    Precursor
    β₂-microglobulin, the light chain of MHC class I
    Setting
    Long-term hemodialysis (not cleared by dialysis membranes)
    Typical sites
    Joints, synovium, carpal tunnel

  • ATTR

    Precursor
    Transthyretin, carrier of thyroxine and retinol
    Setting
    Hereditary mutant forms; wild-type in old age (common after 80, often asymptomatic)
    Typical sites
    Heart: restrictive cardiomyopathy, arrhythmia; nerves

  • AIAPP

    Precursor
    Amylin (islet amyloid polypeptide), co-secreted with insulin
    Setting
    Type 2 diabetes
    Typical sites
    Pancreatic islets (localized)

  • Aβ

    Precursor
    β-amyloid cleaved from amyloid precursor protein (APP)
    Setting
    Alzheimer disease; APP gene on chromosome 21, so most adults with Down syndrome develop early Alzheimer changes
    Typical sites
    Brain plaques, cerebral vessels (localized)

  • ACal

    Precursor
    Calcitonin made by tumour cells
    Setting
    Medullary thyroid carcinoma
    Typical sites
    Within the tumour: “tumour cells in an amyloid background” (localized)

Links to later chapters

L1 p.1Syllabus

This chapter keeps one canonical explanation of amyloid. In the course's Immunopathology chapter, systemic amyloidosis returns as a disorder of the immune system (AL from plasma cells, AA from chronic inflammation); that chapter is not yet built in AL-MED, so this section is the reference. Other threads continue elsewhere:

  • Inflammation and repair: neutrophils, macrophages and scar after infarction; microglia and gliosis in the brain.
  • Hemodynamic disorders: thrombosis, embolism and infarction.
  • Neoplasia: metaplasia → dysplasia → carcinoma; BCL-2 and evasion of apoptosis.

Knowledge check · 1.8

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 5 correct
  1. Q1Metastatic calcificationL1 p.40

    A man with a parathyroid adenoma has a high serum calcium. A renal biopsy shows calcium deposits along the tubular basement membranes of otherwise intact kidney tissue.

    What type of calcification is this?

  2. Q2Amyloid stainingL1 p.46

    Which finding confirms that a tissue deposit is amyloid?

  3. Q3AA amyloidL1 p.47

    A woman with 20 years of active rheumatoid arthritis develops heavy proteinuria. A renal biopsy shows glomerular deposits that are Congo red positive.

    What is the precursor protein?

  4. Q4Localized amyloidL1 p.47–48

    A thyroid nodule contains nests of tumour cells in a background of amorphous, Congo-red-positive material, and the serum calcitonin is high.

    What is the amyloid made from?

  5. Q5Aβ amyloidL1 p.47

    Why do most adults with Down syndrome develop Alzheimer-type changes early?

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