Disorders of Metabolism of Proteins Lipids

8/20/2019 Disorders of Metabolism of Proteins Lipids

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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

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Disorders of Metabolism of Proteins Lipids