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Disorders of metabolism of proteins,
lipids, carbohydrates, nucleid acid.
Impaired metabolism of water.
Impaired metabolism of calcium, iron and
copper
Crystals, concrements, pigments.
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Disorders of metabolism of proteins
• Dystrophy – derrangement of cell metabolism
• Accumulation of metabolite (low-molecular – vacuolisation;
high-molecular – hyaline droplets)
• In some cases – no accumulation of metabolite and only
discrete changes of cell
• Reversible in majority of cases
• Structural changes: (a) enlargement of mitochondria, (b)
vacuolar dystrophy, (c) hyalinne droplets,(d) mucousdystrophy, (e) fibrinoid dystrophy, (f) hyalinosis, (g)
amyloidosis
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• Enlargement of mitochondria: liver, kidney, myocardium,skeletal muscle; microscopicaly – enlargement of cells,
granular cytoplasm (due to enlargement of mitochondria - seeELMI)
• Vacuolar dystrophy (hydropic degeneration): accumulation ofelectrolytes and water, vacuolisation of cytoplasm, oedema
• Hyalinne droplets (hyaline – astructural pink material in
hematoxylin-eosin staining): hepatocytes in viral hepatitis(Councilmann bodies), renal tubuli in albuminuria,plasmocytes in chronic inflammation (Russell bodies)
• Mucous dystrophy: accumulation of mucopolysacharides(mucoviscidosis, alopecia mucinosa, mucopolysacharidoses –
Hurler, Hunter, Sanfilippo, Morqui, Maroteaux-Lamy, beta-glukuronidase deficit , ganglion, myxedema, atherosclerosis,cystic medionecrosis
• Fibrinoid dystrophy/hyalinosis: colagen fibril changes (vesselwall), reticuline fibril changes (endocardium, joints, vessels,
colagenoses, hyalinosis (polyserositis)
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Mallory hyalin
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Mallory hyalin
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Amyloidosis
Clinical classification Amyloid protein Localisation
Primary
(myeloma associated)
AL (Ig light chains) Kidney, spleen, heart, liver,
tongue
Secondary
(reactive – RA, chronic
infections, IBD, tumors)
AA (amyloid associated) Tongue, heart, liver, kidney,
spleen
Senile AS (prealbumin) Heart
Hemodialysis associated AH (
2 mikroglobulin) Kidney
Alzheimer associated A4 (
amyloid) Brain
Endocrine
(medulary thyroid carcinoma)
AE Thyroid
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Disorders of metabolism of lipids
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Sphingolipidosis - ELMI
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Lysozomal storage diseases
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Disorders of metabolism of carbohydrates
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Glycogenoses
• Hepatic type (von.-Gierke)• Myopathic type (McArdle)
• others (Pompe – myocardial)
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Impaired metabolism of water.
• Related to distribution of electrolytes (K+phospates –
intracellulary; Na +Cl+bicarbonates +Mg+sulphates –
extracellulary)
• Intracellular accumulation of water - vacuolar dystrophy
(sponge-like cytoplasm).• Causes: hypoxia, starving, osmotic effects (osmotic
nephrosis), hyperaldosteronism, viroses (herpes).
• Extracellular changes:
a) dehydratation
b) hyperhydratation
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Dehydratation
• Loss of water (hypertonic dehydratation) – diabetes
insipidus
• Loss of water and Na (isotonic dehydratation) –
vomiting, diarrhoea, burns
• Loss of Na (hypotonic dehydratation) – impaired
resorbtion of Na in kidney, hypoaldosteronism
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Hyperhydratation
Hypotonic
Isotonic
Accumulation of fluid:
• Oedema
• Hydrops
• Anasarka
• Transsudation (hydrothorax, hydropericardium, ascites).
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Oedema
• Venostatic (venous thrombosis, gravitation)
• Cardial (left/right ventricle failure)
• Hypoalbuminotic (low oncotic pressure)
• Lymphostatic (elephantiasis)
• Inflammatory (increased capillary permeability -
exsudate)
• Angioneurotic (Quincke)
• Hormonal
• Others (intoxication, hypoxia, etc)
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Impaired metabolism of calcium.
Level of Ca (9-11mg%) is in balance with phosphate iontsand is regulated by parathormone, calcitonin and vitaminD.
Impaired metabolism:
• Dystrophic calcification
• Metastatic calcification (hyperparathyroidism,hypovitaminosis D).
• Calcinosis –
(skin, muscles = myositis ossificansprogressiva, nerves; normal level of Ca).
• Calcifylaxis
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Impaired metabolism of iron
• Fe presented in haemoglobin (73%), myoglobin (11%),
feritin,enzymes and transferin.
• Absorption in small intestine regulated by apoferitin,
efflux of Fe very limited
• Improper acculumation of Fe leads to:
Haemochromatosis – geneticaly related impaired
absorption of Fe (50-times increase). Deposition of
haemosiderin in skin and pancreas (bronze diabetes),
liver (pigmented cirrhosis), heart (failure), salivaryglands, kidney, smooth muscle
Haemosiderosis – hemolysis, increased intake of Fe
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Haemochromatosis
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Haemochromatosis
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Impaired metabolism of copper
Accumulation of copper due to insufficient production of
ceruloplasmin : hepatolenticular degeneration - liver
cirrhosis; destruction of cells in basal ganglia, damage of
proximal tubuli in kidney, Kaiser-Fleischer ring in cornea.
2 clinical variants:
Wilson disease – damage of liver, extrapyramid
symptoms, dementia, start since childhood.
Westfal-Strümpell pseudosclerosis – small neurological
symptoms after puberty
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Crystals
• Uric acid – arthritis uratica (gout) – impaired metabolism
of purines
• Oxalates – colourless crystals in renal tubuli or
myocardium in oxalosis
• Cholesterol – atherosclerosis, postinflammatory
• Paraprotein – renal tubuli in plasmocytoma
• Cystine – cystinosis (Lignac-Fanconi disease) – spleen,
lymph nodes, kidnely, cornea• Charcot-Leyden crystals – destruction of eosinophils
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Gout
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Concrements
Various tissues :Gallbladder, bile ducts, uropoietic system, salivary glands,
pancreas, prostate
Three main factors modulating concrement development:• Increases concentration of substance
• Changes in colloid millieu (inflammation)
• Changes of pH (urine)
• Clinical consequences: obstruction of duct
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Pigments
Autogeneous
• melanin (Addison disease, freckle, naevus, malignant melanoma /albinisms, vitiligo, leukoderma)
• lipofuscin
• haemosiderin
• bilirubin
Exogeneous
• pigmentation by respiratory tract, trauma, gastrointestinal tract,blood
• pneumokoniosis, koniofibrosis
• argyrosis – Ag
• chrysocyanosis – Au