Cell Injury 4 Flashcards
To list the most common examples of cellular and extracellular accumulation. To explain the mechanisms underlying specific types of accumulations. To recognise the morphologic patterns of selected examples of cellular and extracellular accumulations
ACCUMULATIONS
Can be extracellular or intracellular.
Substances can be endogenous or exogenous.
eg. Glycogen, lipids, cholesterol, proteins, minerals, pigments.
INTRACELLULAR ACCUMULATIONS
These are a ‘manifestation of metabolic derangement in cells’.
Intracellular accumulation of abnormal amounts of various substances:
- Normal cellular constituents in excess eg water, lipids, proteins, CHO.
- Abnormal substances. Exogenous- Mineral or products of infectious agents
Endogenous- Product of abnormal synthesis or metabolism. - Pigments
MECHANISMS OF INTRACELLULAR ACCUMULATION
- ABNORMAL METABOLISM leads to production of a normal endogenous substance at a normal or increased rate.
Rate of metabolism is inadequate to remove the substance.
eg. Fat accumulation- Fatty liver. - DEFECT IN PROTEIN FOLDING/TRANSPORT- Leads to accumulation of normal or abnormal endogenous product, due to genetic or acquired defects in metabolism/packaging/transport/secretion.
Abnormal protein can accumulate.
eg. a1 anti-trypsin deficiency -> defects in protein folding
->enzyme accumulates in ER of hepatocytes
-> globular eosinophilic inclusions - LACK OF ENZYME- Normal or abnormal endogenous substrate accumulates due to genetic or acquired defects in protein metabolism/packaging/transport/secretion.
eg. Complex lipid/CHO substrate cannot be broken down to soluble products due to lack of enzyme, so it builds up in lysosomes -> LYSOSOMAL STORAGE DISORDERS. - INGESTION OF INDIGESTIBLE MATERIALS- An abnormal exogenous substance is deposited and accumulated because the cell lacks enzymatic machinery to degrade the substance and the ability to transport it to another site.
eg. Accumulation of carbon particles and non metabolisable particles such as silica particles.
HEPATIC LIPIDOSIS
Fatty liver.
Accumulation of triglycerides or other lipids (neutral lipids, cholesterol) within parenchymal cells.
Can occur in other organs, but liver is critical in lipid metabolism and disposition.
Clinically, manifests as altered liver function.
CAUSES/MECHANISMS OF HEPATIC LIPIDOSIS
- Excessive intake/delivery of free fatty acids from gut or adipose tissue.
- Decreased B-oxidation of fatty acids to ketones and other substances because of mitochondrial injury (due to toxins, hypoxia)
- Impaired apoprotein synthesis (due to CCl4 toxicity, aflatoxicosis)
- Impaired combination of triglycerides and protein to form lipoprotein. UNCOMMON IN DOMESTIC ANIMALS.
- Impaired release/secretion of lipoproteins from hepatocyte. UNCOMMON IN DOMESTIC ANIMALS.
HEPATIC LIPIDOSIS IN DOMESTIC ANIMALS
Most commonly caused by conditions causing increased mobilisation of body fat stores (due to increased demand for energy over a short period of time).
Seen in dairy cows in late pregnancy (pregnancy toxaemia), early lactation (ketosis).
Can be caused by nutritional disorders- Obesity, protein calorie malnutrition, starvation,
Genetically inherited disorders- Glycogen storage disease, Wilson’s disease, Endocrine- Diabetes Mellitus
Feline Fatty Liver Syndrome
Fat Cow Syndrome
GROSS APPEARANCE OF FATTY LIVER
Enlarged, rounded edges
Pale yellow discolouration (icterus)
Soft, friable
Greasy texture
MICROSCOPIC APPEARANCE OF FATTY LIVER
Hepatocytes have intracytoplasmic round, sharply demarcated VACUOLES which displace the nucleus to the periphery of the cell.
Oil red 0 stain of fresh frozen sample shows vacuoles in red.
HEPATIC GLYCOGEN ACCUMULATION
Excessive glycogen storage/overload.
Caused by- Abnormal glucose/glycogen metabolism.
- Diabetes mellitus- Glycogen accumulation in hepatocytes, renal proximal tubule epithelium, B cells of Islets of Langerhans (pancreas)
- Prolonged corticosteroid/glucocorticoid treatment- STEROID HEPATOPATHY.
STEROID HEPATOPATHY- GROSS APPEARANCE OF LIVER.
Enlarged, rounded edges, pale beige to tan, FIRM, NON GREASY (cf. fatty liver)
MICROSCOPIC APPEARANCE OF STEROID HEPATOPATHY
Hepatocytes are swollen, with vacuolated cytoplasm.
Possible peripheral displacement of nucleus.
When glycogen is overloaded in hepatocytes (in steroid hepatopathy + other accumulative conditions), it forms intracytoplasmic irregular clear spaces with INDISTINCT outlines.
OTHER RELEVANT INTRACELLULAR ACCUMULATIONS
INTRACYTOPLASMIC HYALINE PROTEIN ACCUMULATIONS- Resorption droplets in renal tubular epithelial cells (due to excess glomerular protein filtration and resorption by tubular epithelium)
Russell bodies seen in plasma cells- Inclusion bodies containing immunoglobins due to excessive production.
VIRAL INCLUSION BODIES- Can be intracytoplasmic or intranuclear.
LEAD POISONING- Irregular intranuclear inclusion bodies are seen in renal tubule epithelium.
EXTRACELLULAR ACCUMULATIONS
Eosinophilic/hyaline substances.
- Hyaline casts in lumen of renal tubules (proteinuria).
- Plasma proteins in vessel walls.
- Old scars.
- Thickened basement membranes eg. glomerulonephritis.
- Hyaline membranes of alveolar walls (in acute alveolar damage)
- Hyaline microthrombi
- Amyloid
See slides.
AMYLOIDOSIS
Amyloid is an eosinophilic amorphous hyaline substance.
If deposited extracellularly, it causes compression of adjacent parenchymal cells, causing atrophy or death from compression and/or ischaemia.
Can be primary or secondary.
PRIMARY AMYLOIDOSIS
Seen in plasma cell dyscrasias.
AL AMYLOID- Light chain; derived from immunoglobin light chains.
SECONDARY AMYLOIDOSIS
Seen secondary to chronic inflammation, due to chronic antigenic stimulation with cell breakdown.
aka. Reactive systemic amyloidosis.
AA AMYLOID.
MOST COMMON FORM IN ANIMALS.
Deposits in kidney, liver, spleen, lymph nodes.
SERUM AMYLOID ASSOCIATED (SAA)
Secondary amyloidosis is caused by excessive or prolonged production of acute phase protein by the liver, in response to IL-1, IL-6 (inflammatory mediators).
Associated with chronic inflammatory processes.
Cattle- Chronic suppurative pneumonia, hoof abscesses, traumatic reticulopericarditis, visceral abscesses.
Horse- Visceral abscesses.
Cats, birds- Idiopathic amyloidosis.
In birds, amyloid accumulates in the space of Disse in the liver.
RENAL AMYLOIDOSIS
Grossly, large, pale waxy kidneys, swollen cortex, may see pale pinpoint foci (glomeruli)
May see protein losing nephropathy.
Subcutaneous oedema, brisket oedema, bottle jaw, ascites or anasarca.
LOCALISED AMYLOIDOSIS
Involves a single organ or tissue.
HORSE- Nasal vestibule or rostral portion of nasal septum and conchae.
CAT- Pancreatic islets.
TUMOUR ASSOCIATED AMYLOIDOSIS
Associated with specific tumour types.
- AMYLOID PRODUCING ODONTOGENIC TUMOURS (APOTs)
- AL AMLYOID is associated with PLASMA CELL TUMOURS
- AMYLOID is associated with thyroid c-cell tumours.
PIGMENTS
Exogenous- Carbon particles, carotenoid pigments, tetracycline.
Endogenous- Melanin, haemoglobin/haemolgobin derived breakdown pigments, lipofuscin.
LUNG ANTHRACOSIS
Seen in aged dogs due to pollution inhalation over it’s lifetime.
Disseminated blackish visible on pleural surface of lung/in parenchyma.
Histologically, peribronchiolar aggregrates of macrophages engulfing black carbon particles.
Exogenous pigment.
CONGENITAL MELANOSIS
Seen in meninges, lungs and other organs of various animals.
Melanin is a black pigment normally present in skin melanocytes; it can build up in other cells.
Endogenous pigment.
eg. Pig lung- Ectopic aggregates of melanocytes- Multiple irregular areas of blackish discolourisation on pleural surface.
HAEMOGLOBIN
Breakdown of Hb yields various endogenous pigments. HAEMOSIDERIN HAEMATIN- ONLY PRODUCED PATHOLOGICALLY PORPHYRIN BILIRUBIN HAEMATOIDIN
Except for haematin, these are produced normally, but can accumulate excessively.
HAEMATIN
Only produced pathologically in cases of PARASITIC INFECTION.
eg. Fluke infestation can cause haematin accumulation in the bile duct.
Dark colour.
HAEMOSIDERIN
Golden yellow or brown pigment.
Contains oxidised iron (Fe3+)- Positive staining with Perl’s Prussian blue.
Produced in organs involved in RED CELL BREAKDOWN.
Local haemosiderosis can be seen- Bruising.
General haemosiderosis- Haemolytic anaemia.
LIPOFUSCIN
‘Wear and tear pigment’
Accumulates in post mitotic cells (neurons, myocytes)
Slowly dividing cells also (hepatocytes)
Is the FINAL UNDEGRADEABLE REMNANT OF AUTOPHAGOCYTOSIS.
Proteins, lipids, little carbohydrate.
Unremoveable- Accumulates in lysosomes.
Endogenous.
PATHOLOGIC MINERALISATION/CALCIFICATION
Calcium salts are deposited in dead/degenerating/dying or normal tissues.
They are usually harmless, but indicate previous injury.
White, gritty.
Stain blue (basophilic) with H&E.
DYSTROPHIC CALCIFICATION
Associated with necrosis
Most prominent in caseous, coagulative and fat necrosis.
Minimal in liquefactive necrosis
Dead/dying cells cannot regulate cytoplasmic Ca influx -> Ca accumulates in mitochondria.
METASTATIC CALCIFICATION
Occurs in normal tissues SECONDARY TO HYPERCALCAEMIA.
Basic abnormality causes entry of large amounts of Ca in to cells.
Ca ions precipitate on organelles, particularly mitochondria.
COMMON CAUSES OF METASTATIC CALCIFICATION
Renal failure
Vitamin D toxicosis
Parathyroid hormone- Hyperparathyroidism
PTH-related protein (PTH-rp)- Paraneoplastic hypercalcaemia
Destruction of bone from primary or metastatic neoplasias.
See slides.
Von Kossa stain for Ca salt deposits- Dark colour.
Basophilic on H&E- Very purple.
GOUT
Deposition of sodium urate crystals or urates in tissues, forming tophi.
Humans- Lack uricase.
Birds and reptiles- Excrete uric acid as semisolid urates which can accumulate in tissues.
Not reported in other domestic animal species.
2 forms of gout are seen in birds and reptiles- Articular and Visceral types.
ARTICULAR TYPE GOUT
Rare, seen as urate deposition in and around the joints.
VISCERAL TYPE GOUT
Caused by Vitamin A deficiency, renal damage, high protein diet.
- Visceral serosa, particularly parietal pericardium. Covered with a thin layer of grey granules- Gross appearance is diagnostic.
- Kidneys- Urate deposits in renal tubules and ureters.
FIBRINOID NECROSIS/FIBRINOID DEGENERATION
Fibrinoid change of the vascular wall.
Results from deposition of- Immunoglobins
Complement
Plasma proteins (fibrin)
in to the VESSEL WALL. Generally affects the INTIMA and MEDIA.
Commonly observed in immune mediated vasculitides (vasculitis)
Amorphous, dense, ‘smudgy’ eosiniphilic material effaces the structure of the vessel wall.
Frequently characterised by the accumulation of fine to coarse granular basophilic material resulting from karyorrhexis of inflammatory cells.
