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Incoming links: Amyloid
Historical “amyloid disease” denotes the waxy or lardaceous visceral change, especially in the spleen, liver and kidneys; modern amyloidosis denotes deposition of misfolded protein fibrils. The old descriptive appearance and the modern chemical explanation must be kept distinct.
In nineteenth-century usage the affected organs could be enlarged, firm and unusually translucent or wax-like on section. The name amyloid means starch-like. The historical chemical argument relied on colour reactions with iodine and sulfuric acid, suggesting affinity with starch or cellulose. Such a reaction was a clue to recognition, not a modern identification of the deposited substance. Rudolf Virchow's 1856 account explicitly discusses the waxy change of the spleen, liver and kidneys, and its occurrence with longstanding destructive disease.[ref]
On the Course of the Amyloid Degeneration by Rudolf Virchow. 1856 English abstract, pp. 380–383, opening account of visceral sites and chronic disease
The three principal visceral examples can be described more precisely:
- In the spleen, deposits in the splenic white pulp may produce translucent granules, the so-called sago spleen. More diffuse involvement gives a widespread lardaceous appearance.
- In the liver, deposits along the hepatic sinusoids can compress adjacent hepatocytes; extensive deposition may produce a large firm liver.[ref]Hepatic amyloidosis: morphologic differences between systemic AL and AA types. Abstract, autopsy examination of 286 livers; sinusoidal and portal patterns
- In the kidney, deposits in glomeruli, blood vessels and sometimes the interstitium interfere with function. Involvement of the glomeruli explains the albuminuria of Question 1; it may progress to nephrotic syndrome and kidney failure.
The distribution is not confined to those three organs. Amyloidosis can also affect the gastrointestinal tract, heart, blood vessels and other sites; the pattern depends on the precursor protein. Modern examples include AA amyloidosis associated with sustained inflammation, AL amyloidosis involving immunoglobulin light chains, and transthyretin amyloidosis. This classification is a present-day explanation, not a list of molecular diagnoses asserted for unnamed 1867 patients.[ref]
Amyloidosis by Merck Manual Professional Edition. Introduction; Etiology, systemic types and common sites of deposition
Modern confirmation uses histology with Congo red and examination with a polarizing microscope, followed by identification of the deposited protein, for example with mass spectrometry. The characteristic birefringence supports identification of amyloid; typing distinguishes biologically different diseases. These are later laboratory methods, not apparatus available to the candidate in 1867.[ref]
Modern hypertrophy means enlargement of individual biological cells; hyperplasia means an increase in their number. Both can enlarge an organ, and both can occur together. The historical question requires care because nineteenth-century authors sometimes included “numerical hypertrophy” within the broader discussion of growth. Rudolf Virchow's 1860 English edition explicitly distinguishes enlargement of existing elements from multiplication of elements, using simple and numerical hypertrophy for these different processes.[ref]
Cellular Pathology by Rudolf Virchow (1860). Lecture III, pp. 93–95, Hypertrophy and Hyperplasy and Degenerative New Formations
At the minute structural level, true hypertrophy entails increased cellular substance and, in a contractile biological cell, more contractile apparatus. Enlarged cell nuclei can accompany it, but a large cell nucleus alone does not prove a proportional increase in functional tissue. Increased cell number belongs to hyperplasia. Apparent organ enlargement from oedema, fatty infiltration, amyloid or a tumour must be distinguished from a coordinated increase of the organ's working tissue.[ref]
Cellular Pathology in Pathology: The Big Picture. Hypertrophy and Hyperplasia; morphological distinction and increased contractile protein in pressure-loaded myocardium
The clearest early-to-late examples compare adaptation with the possible effects of continued overload:
- In the heart, sustained hypertension or aortic stenosis makes the left ventricle work against greater resistance. Initially its cardiomyocytes enlarge and the wall thickens, with enlarged cell nuclei and increased contractile proteins. With prolonged pathological stress there may be fibrosis, loss of cardiomyocytes, ventricular dilatation and heart failure. The late enlarged failing heart need not have a uniformly thick wall; hypertrophy and dilatation describe different structural changes.[ref]Stress Kinase Signaling in Cardiac Myocytes. Cardiac hypertrophy, physiological adaptation versus pathological hypertrophy and progression to heart failure
- In the urinary bladder, persistent outflow obstruction increases the work of the detrusor muscle. Enlargement of smooth muscle bundles thickens the wall and can produce bladder trabeculation. With prolonged obstruction, fibrosis, dilatation and incomplete emptying can coexist with the initial growth. This is a progression possible under sustained pathological load. Human studies describe early hypertrophy and subsequent compensation or decompensation; progression is not an inevitable fate of all enlarged smooth muscle.[ref]Progressive bladder remodeling due to bladder outlet obstruction. Results; Discussion, proposed three-stage model and its evidential limits
- In skeletal muscle, increased use enlarges existing fibres through additional contractile material. Later development of this physiological response produces larger, stronger fibres; it does not inherently require fatty degeneration. If an apparent muscular enlargement is mainly fat or connective tissue, that is pseudohypertrophy.
These illustrations compare different outcomes rather than proposing a universal stage in which every enlarged organ degenerates.[ref]
Hypertrophy and hyperplasia in Underwood's Pathology: a Clinical Approach. Adaptive responses to increased demand; physiological hypertrophy and hyperplasia
[ref]Cellular Pathology in Pathology: The Big Picture. Hypertrophy, physiological and pathological examples
A second set illustrates growth in organs whose biological cells can also divide. The pregnant uterus combines marked enlargement of smooth muscle biological cells with an increase in their number; after delivery it undergoes involution. An enlarged remaining kidney after loss of its partner exemplifies compensatory growth. In a modern rat experiment comparing neonatal, weanling and adult animals after removal of one kidney, the younger groups showed greater compensatory growth; that experimental comparison does not make an age-independent prediction for every human kidney.[ref]
Age-dependent characteristics of compensatory renal growth. Abstract, comparison of neonatal, weanling and young adult rats
Thus organ size alone cannot distinguish the cellular processes: compare cell dimensions, numbers and tissue composition by histology.[ref]Hypertrophy and hyperplasia in Underwood's Pathology: a Clinical Approach. Physiological hypertrophy and hyperplasia, uterine growth; compensatory growth