Cell Injury: Intracellular and Extracellular accumulations Flashcards Preview

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Flashcards in Cell Injury: Intracellular and Extracellular accumulations Deck (28):

Intracellular accumulations

Manifestation of metabolic derangement in cells 

Intracellular accumulation of abnormal amounts of various substances

1. normal cellular constitutents accumulating in excess (water, lipids, proteins ,CHO)

2. abnormal substance, either exogenous (mineral or product of infectious agents) or endogenous (product of abnormal synthesis or metabolism)

3. 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=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.



Metastatic calcification

occuring in normal tissues secondary to hypercalcemia

basic abnormality--> entry of large amounts of calcium ions in to cells. Calcium ions precipitate on organelles, particularly mitochondria


Common causes of metastatic calcification

renal failure: retention of phosphates-->secondary renal hyperparathyroidism and hypercalcemia. Calcium deposited in gastric mucosa, kidney and alveolar septa. 

Vitamin D toxicosis: ingestion of calcinogenic plants by herbivores-->severe soft tissue mineralization, chiefly involving aorta, heart and lungs. In the heart, endocardium of RA, LA and LV is often strikingly mineralized.

Acute vitamin D toxicosis in dogs and cats: ingestion of rodenticidies containing cholecalciferol: mineralization of intestinal mucosa, vessel walls, lungs and kidneys

Hyperparathyroidism, PTH related protein: Primary HyperPTH is rare. Secondary (renal) is most common. 

Hypercalcemia and high PTH related protein levels can be associated with canine malignant lymphomas and canine adenocarcinomas of apocrine glands of anal sacs. intestinal mucosa, vessel walls, lungs and kidney are mineralized

Destruction of bone from primary or metastatic neoplasms.



deposition of sodium urate crystals or urates in tissues

Humans lack uricase

birds and reptiles- excrete uric acid as semisolid urates

2 forms of bird and reptile gout: 1) articular type (rare) and 2) visceral type (vit. A deficiency, high protein diet, renal injury)- serosa covered with a thin layer of grey granules, urate deposits in renal tubules and ureters. 


Fibrinoid change of vascular wall

Fibrinoid necrosis or degeneration: resulting from deposition of immunoglobulins, complement, plasma proteins in the vessel wall (affects intima and media). Commonly observed in immune-mediated vasculitides

Deposition of amorphous, dense, smudgy eosinophilc material effacing structure of vessel wall.

Frequently characterized by accumulation of fine to coarse granular basophilic material resulting from nuclear fragmentation (karyorrhexis) of inflammatory cells.