Cell Injury: Intracellular and Extracellular accumulations Flashcards
Intracellular accumulations
Manifestation of metabolic derangement in cells
Intracellular accumulation of abnormal amounts of various substances
- normal cellular constitutents accumulating in excess (water, lipids, proteins ,CHO)
- abnormal substance, either exogenous (mineral or product of infectious agents) or endogenous (product of abnormal synthesis or metabolism)
- pigments
Mechanisms of intracellular accumulations
1) abnormal metabolism: normal endogenous substance produced at normal or increased rate, but rate of metabolism is inadequate to remove it
2) defect in protein folding, transport: normal or abnormal endogenous substance accumulates because of genetic or acquired defects in metabolism, packaging, transport or secretion.
3) lack of enzyme: normal or abnormal endogenous substance accumulates due to enzyme defects
4) ingestion of indigestible materials: abnormal exogenous substance is deposited and accumulats because the cell lacks 1) enzymatic machinery to degrade substance and/or 2) ability to transport it to other sites.
Hepatic lipidosis (fatty liver)
Lipidosis= accumulation of TGs or other lipids within parenchymal cells. May occur in multiple tissues but liver is a critical organ in lipid metabolism and disposition.
Clinical manifestation of lipidosis is generally observd as altered liver function (increased liver enzymes, icterus)
Causes/mechanisms of hepatic lipidosis
1) excessive intake/delivery of FFAs either from gut or from adipose tissue
2) decreased beta-oxidation of FAs to ketones and other substances because of mito injury (toxins, hypoxia)
3) impaired synthesis of apoprotein (CCl4 toxicity, aflatoxicosis)
4) impaired combo of TGs and protein to form lipoprotein (uncommon in domestic animals)
5) impaired release (secretion) of lipoproteins from hepatocyte (uncommon in domestic animal)
Hepatic lipidosis in domestic animals
Most commonly from conditions causing increased mobilization of body fat stores due to an increased demand for energy over a short duration.
In dairy cows: late pregnancy (toxemia) or early lactation (ketosis)
Nutritional disorders: obesity (increased dietary lipid transport or mobilization from adipose tissue); protein-calorie malnutrition (impaired apolipoprotein syntehsis); starvation (increased mobilization of TGs); genetically inherited disorders; endocrine disorders (diabetes mellitus- increased mobilization of TGs)
Gross and microscopic appearance of hepatic lipidosis
gross: liver enlarged with rounded edges, pale yellow, soft and friable with greasy texture
Microscopic: hepatocytes with inractyoplasmic round, sharply demarcated vacuoles displacing nucleus at periphery.
Hepatic glycogen accumulation
Causes of excessive glycogen storage/ overload
Abnormal glucose or glycogen metabolism
Diabetes mellitus: glycogen accumulation in hepatocytes, renale proximal tubule epithelium, beta-cells of pancreatic islets of langerhans
Prolonged corticosteroid/glucosteroid tx “steroid hepatopathy”
Gross appearance of steroid hepatopathy
in dog: enlarged, rounded edges, pale beige to tan in color, firm, non-greasy.
swollen hepatocytes with vacuolar change in cytoplasm.
Glycogen overload histopathology
glycogen forms intracytoplasmic irregular clear spaces with indistinct outlines
hepatocyte nucleus remains centrally located
With very large amounts of glycogen, i.e. in steroid hepatopathy, more prominent cytoplasmic selling and possibly periperhal displacement
Intracytoplasmic hyaline protein accumulations
resorption droplets in renal tubular epithelial cells (excess glomerular filtration and resorption by tubular epithelium)
Russel bodies in plasma cells (immunoglobulin accumulation resulting from excessive production)
Viral inclusion bodies
Intracytoplasmic: poxvirus, canine distemper (also intranuclear)
Intranuclear: herpesvirus, adenovirus, parvo, papillomavirus
Lead poisoning
Irregular intranuclear inclusion bodies in renal tubule epithelium
Extracellular accumulation
Eosinophilic/hyaline substances
Hyaline casts in the lumen of renal tubules (proteinuria)
Plasma proteins in vessel walls
Old scars: decreased cellularity of fibrous tissue- bundles of collagen fibers condense and become hyalinized
Thickened basement membranes
Hylaine membranes of the alveolar walls (acute alveolar damage)
Hyaline microthrombi in DIC, often visible in glomerular capillaries and pulmonary alveolar capillaries
AMYLOID
Amyloidosis
amyloid=eosinophilic amorphous hyaline substance
gets deposited extracellulalry and causes compression of adjacent parenchymal cells, causing atrophy or death from compression/ischemia.
Diverse group of glycoproteins–>beta-pleated sheet protein configuration, responsible for the characteristic congo red staining.
Primary amyloidosis
plasma cell dyscrasias (plasma cell tumours); AL amyloid derived from immunoglobulin light chains
Secondary amyloidosis
reactive systemic amyloidosis (AA amyloid)
Secondary to chronic inflammation- chronic antigenic stimulation with cell breakdown
-most common form in animals
deposits in kidney (proteinuria), liver, spleen and LNs.
Serum Amyloid Associated (form of secondary amyloidosis)
excessive or prolonged production of acute phase protein by liver (in response to IL-1 and IL-6) –> associated with chronic inflammatory process.
Cattle: chronic suppurative pneumonia, hoof abscesses, traumtic reticulopericarditis, visceral abscesses
Horse: visceral abscesses
Cats, birds: idiopathic amyloidosis
Birds: amyloid accumualtion in space of Disse in liver.
Renal amyloidosis
Gross appearance: large, pale, waxy kidneys with swollen cortex +/- pale pinpoint foci (glomeruli)
Functional and clinical consequences: +/- protein losing nephropathy, subcut oedema, brisket oedema, bottle jaw, generalized edema, ascites
Localized amyloidosis
involving a single organ or tissue
horse: nasal vestibule or rostral portion of nasal septum and turbinates
Cat: pancreatic islets
tumor-associated amyloidosis: association with specific tumor types
Pigments-exogenous deposits
Carbon particles–>anthracosis in lung of aged dog (disseminated black dots)
carotenoid pigments–>fat soluble pigments of plant origing (vit A precursrs)
Tetracyline (ABX)–> yellowish, pink discoloration of teeth
Pigments: endogenous deposits
Melanin: black pigment normally present in skin melanocytes–> congenital melanosis (blackish discoloration on pleural surface of lung for example) in meninges, lungs or other organs
Hb and Hb breakdown derived pigments
Lipofuscin (wear and tear pigment): accumulates in post-mitotic cells (neurons, myocytes) and slowly dividing cells (hepatocytes), final undegradable remnant of autophagocytosis, unremovable (accumulates in lysosomes)
HB breakdown derived pigments
Hemosiderin–> excessive RBCs destruction–> golden yellow or brown pigment, contains iron in oxidized state. Local hemosiderosis with bruising. Generalized hemosiderosis with hemolytic anemia
Hematin–>parasitic infections (pathological)
Porphyrin–> rare congenital conditions
Bilirubin–> excreted through liver
Hematoidin–> sites of recent hemorrhage
Pathologic mineralization/calcification
Calcium salts deposited in dead, degenerating/dying or normal tissues
Usually harmless but indicator of previous injury
Affected areas are white and gritty
Calcium salts stain blue (basophilic) with H&E
Dystrophic calcification
Associated with necrosis: most prominent in coagulative, caseous necrosis, and also in fat necrosis
Minimal with liquefactive necrosis.
Dead/dying cells can’t regulate cytoplasmic influx and calcium accumulates in mitochondria.
