Lecture 13 Flashcards
What causes cell degeneration
- the result of sublethal injury
- results in reversible morphologic change
What is essential to homeostasis
The cellular membranes are essential to homeostasis by
regulating what substances enter and leave the
cell and its organelles
Causes of cell injury
- Hypoxia
- Impaired blood flow – cardiac disease/ ischemia
- Impaired O2 transport – respiratory disease/ anemia/ toxins
- Physical agents
- trauma, thermal, UV radiation, ionising radiation
- Microbes
- viruses, bacteria - toxins, fungi, helminths, protozoa
- Inflammation and immunologic dysfunction
- Nutritional imbalances
- Genetic derangement
- eg. lysosomal storage diseases
- Workload imbalance
- Chemicals, drugs, toxins
- Aging
- Combination - potentiating
Hypoxia
- Impaired blood flow – cardiac disease/ ischemia
* Impaired O2 transport – respiratory disease/ anemia/ toxins
Physical agents Causes of cell injury
• trauma, thermal, UV radiation, ionising radiation
Microbes Causes of cell injury
• viruses, bacteria - toxins, fungi, helminths, protozoa
What is the cell injury mechanism activated by
different injurious stimuli • ATP depletion • Oxygen derived free radicals • Permeabilization of cell membranes • Mitochondrial damage • Disruption of biochemical pathways • DNA damage • Often overlapping mechanisms
how does ATP depletion work
Ishemia(reduce blood) causes reduction in oxidative phosphorylation, thus reduce ATP
How does Oxygen derived free radicals work
radiation toxins reperfusion
What do you see in Reversible injury
swelling of the cell Damage to membrane ion pumps swollen mitochondria, ER, lysosomes changes to plasma membrane Altered protein synthesis accumulation of metabolites Nuclear changes clumped chromatin
What happens in hypoxia
• Largely reflects ↓ATP → impaired Na+ /K+ - ATPase pumps • → influx Na+ , Ca++ accompanied by H2O • → efflux K+ , Mg++ • ↓ATP → switch to anaerobic metabolism • → ↓ glycogen in cell • → ↓ pH
Where does hydropic degeneration happen
– liver, renal tubular epithelium, pancreatic
islet cells
Where does Ballooning degeneration happen
epidermis and upper alimentary tract –
keratinocytes
Where does Cytotoxic oedema happen
astrocytes in the CNS
How does hydropic degeneration work
Due to hypoxia, sodium channel pumps in H2O and causes water to move to cytosol and cytocavitary system and all other organelles due to osmotic pressure. Which then end up having hydropic degeneration
When does ballooning degeneration develop
before vesicle formation
When might there be a chance that epithelial cells of the stratum spinosum contain intracytoplasmic eosinophilic
parapoxvirus inclusions
earlier stage
When does cytotoxic oedema occur
Accumulation of ammonia
What happens when there is an accumulation of ammonia?
- ammonia taken up by astrocytes > converted
to osmotically active glutamine, which causes cytotoxic astrocytic swelling >
rise in intracranial pressure and compromised astrocytic function
What dictates the result after acute cell swelling
- Depends upon
- number of cells affected and
- regenerative capabilities of the cell – brain and heart vs liver and kidney
What are the outcomes of injurious insult
- Recover and regain function – Back to normal after removal
- If severe, lengthy or repetitive injury see
- Impaired cell metabolism with intracellular accumulations
- Irreversible cell damage and cell death
What make cell can accumulate intracellular material via
• Disturbance/s to metabolism → accumulation of by-products • Genetic mutations → accumulation of abnormal product OR inability to process intracellular by-product • Exogenous substances
Is intracellular accumulation harmful
Can be innocuous but may be harmful
What Lipidosis/ Steatosis/ Fatty change affect
a range of tissues – liver especially
What are the possible mechanisms for Lipidosis/ Steatosis/ Fatty change
- ↑ delivery of FFAs
- ↓ utilization of FFA
- ↓ synthesis of apoprotein
- ↓ impaired lipoprotein formation
- ↓ release of lipoproteins
- and 5. most common sites – require energy and protein
What is one way to see if If lipidosis is severe
the affected
tissue may float in formalin fixative
What does diffuse lipidosis usually indicates
the increased mobilization of free fatty acids in association with
negative energy balance resulting in mobilization of fat reserves
eg periparturient cow – ketosis or pregnancy toxaemia in sheep
Where are the two major sight of glycogen storage
liver and skeletal muscle
What is the most common cause of glycogen
accumulation in hepatocytes of dogs
Hyperadrenocorticism
What causes Excess cortisol in dogs
• corticosteroid drugs • functional ACTH-producing pituitary tumour • functional cortisol- producing adrenocortical • Induces hepatocellular transcription of glycogen synthetase
What is the diagnosis for vacuolar hepatopathy
• Hydropic degeneration, glycogen accumulation, lipid accumulation,
ballooning degeneration, other
• Not possible to differentiate the cause of hepatocellular vacuolation
What is glycogen storage disease
- Inherent disorders of glycogen metabolism – Various types
- Pompe’s Disease – def lysosomal acid maltase (acidic α-glucosidase)
- Inherited – autosomal recessive - esp Brahman and Shorthorn
Is Lysosomal storage diseases inherited
- Inherited or induced defects of metabolism
- Genetic defect
- Exogenous toxin
What is Lysosomal storage diseases
Accumulation of storage material in lysosomes
• Range of storage materials - lipids and carbohydrates
What are the early clinical signs of Congenital alpha-mannosidosis
early – blindness, ataxia, head tremors, intention tremors
What causes Acquired alpha-mannosidoses
- Swainsonine intoxication
* plants such as Swainsona species (Darling pea)
What is Acquired alpha-mannosidoses
• indolizidine alkaloid (swainsonine)
• inhibits lysosomal α-mannosidase
• Induces clinical disease and lesions to
congenital α-mannosidase deficiency
What is amyloid
• Extracellular deposits of fibrillar protein
tissue damage and functional compromise
• Abnormal folding of proteins which become insoluble and aggregate
to form fibrils (amyloid)
What happen to the abnormal folding of proteins in amyloid
• Deposited in the extracellular space
What are the two forms of amyloid proteins
normal proteins with an inherent tendency to fold improperly
mutant proteins that are prone to misfolding and aggregation
What is AA amyloid
AA amyloid
• most common form in animals – reactive – associated with chronic inflammation
• formed via serum amyloid A – acute phase protein via liver/inflammation
What is AL amyloid
- most common form in humans – occasionally animals
* formed via λ or occasionally κ Ig light chains – plasma cell neoplasia
What is IAPP amyloid
- deposited in pancreatic islets of cats and primates
* formed via islet amyloid polypeptide – secreted by β cells in pancreas - ?
What is Aβ amyloid
• Cerebral plaques and cerebral blood vessels – Alzheimer’s in humans and dementia
in dogs
Where does AA amyloid in absysinnians deposit to
– renal glomeruli and medulla – renal protein loss and kidney
failure
Where does AA amyloid in siamese cats deposit to
– liver – hepatic rupture
Where does AA amyloid in shar peis deposit to
renal medulla – renal protein loss and kidney failure
How is pancreatic amyloidosis formed by
Formed by islet amyloid polypeptide
Produced by the β- cells
Deposition of amyloid in pancreatic islets (Islets of Langerhans) with loss of β- cells
What is tunica intima in the artery
- endothelium
- basement membrane
- internal elastic lamina
What is tunica media in the artery
- smooth muscle
- collagen, reticular, and elastin fibres
- external elastic lamina
What is tunica adventitia in the artery
- connevtive tissue
- vasa vasorum (microvessels)
- lymphatic vessels
- nerve fibre
- peripheral layer
What causes Fibrinoid change
Damage to endothelial cells, basement
membrane or smooth muscle of media
What happens when there is fibrincoid change
Leakage of immunoglobulin, fibrin, complement
into blood vessel wall forming fibrinoid
Deeply eosinophilic deposits = fibrinoid change
Vascular damage can reflect vasculitis arising in
association with
sepsis, viral infection, endotoxemia
What is flame figures
• Seen in association with eosinophilic inflammation
• Discharged eosinophil granules and nuclear debris
encrusted on intact collagen
• Mantle of surrounding macrophages = campfire
What are some Range of hypersensitivity reactions to agents
arthropod bites
food and environmental allergens
fungal infections
equine and canine mast cell tumors
Which animal is most common to have flame figures
Especially in the cat and horse
What is Eosinophilic granuloma complex in cats
EGC is a group of lesions – range of locations
Characterized by florid eosinophilic inflammation often with flame figures
What can intracellular accumulations be
- lipid, glycogen, protein, pigment
What is FFA
free fatty acids
what can cause a large accumulation of glycogen
Hyperadrenocorticism
What cause glycogen storage disease
The inability for lysosoman acid maltase to metabolize glycogen
is SAA protein caused by chronic inflammation
yes
