CELLULAR BIOLOGY - Cell Injury Flashcards
List the five ways cells can respond to adaptive change
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
Dysplasia
How are permanent cells repaired?
Permanent cells are repaired through replacement by connective tissue causing a loss of specialised function
What is hypertrophy?
An increase in organ/tissue size due to an increase in cell size
Which cells is hypertrophy seen in?
Stable and permanent cells
What are the physiological causes of hypertrophy?
Increased mechanical or metabolic workload
Hormone stimulation
Give an example of hypertrophy caused by increased mechanical workload?
Hypertrophy cardiomyopathy
Give an example of hypertrophy caused by hormone stimulation?
Hypertrophy secondary to hyperthyroidism
What age and sex of cat is predisposed to Feline Hypertrophic Cardiomyopathy?
Middle aged male cats
What are the pathological causes of hypertrophy?
Abnormal increase in hormone stimulation
Physical obstruction
Genetics
What are the limiting factors of hypertrophy?
Limited vascular and nutritional supplies for the enlarged cells
What is hyperplasia?
An increase in organ/tissue size due to an increase in the number cells (proliferation)
Which cells is hyperplasia seen in?
Labile and stable tissues
What are the causes of hyperplasia?
Hormonal stimulation
Growth factors
Pathological
Give an example of hormone induced hyperplasia. What is the clinical significance of this condition?
Cystic endometrial hyperplasia which can progress to a pyometra
Give an example of infection induced hyperplasia
Porcine proliferative enteropathy
What is atrophy?
A decrease in organ/tissue size due to a decreased nutrient supply and/or function leading to decreased protein synthesis and increased protein and organelle breakdown
What are the causes of physiological atrophy?
Altered/decreased hormonal stimulation
Apoptosis of individual cells
What are the causes of pathological atrophy?
Nutrient deficiency (cachexia)
Disuse
Denervation
Pressure
Loss of endocrine stimulation
What is denervation atrophy?
The atrophy of skeletal muscle fibres due to neural damage
What is indicated by post mortem serous atrophy of fat?
Suggests starving/emaciation but it can be caused by a wide range of other things
What is metaplasia?
The replacement of an adult cell type with another adult cell type
What is adaptive substitution in regards to metaplasia?
The replacement of sensitive cell types with another cell type that is able to withstand adverse environments
What are some of the causes of metaplasia?
Chronic chemical injury
Chronic mechanical injury
Chronic inflammation
Vitamin A deficiency
Hormonal stimulation
What is dysplasia?
The disordered arrangement of epithelial cells with loss of differentiation, loss of cell polarity and features of atypia (abnormalities)
What is hypoplasia?
The incomplete or underdevelopment of an organ/tissue leading to a below average number of cells
What is a common example of hypoplasia which frequently leads to reduced fertility?
Unilateral or bilateral testicular hypoplasia
What is aplasia/agenesis?
The complete lack of organ/tissue development
What are the seven causes of cell injury?
Oxygen deprivation
Physical agents
Chemical agents and drugs
Infectious agents
Immunologic dysfunction
Genetic defects
Nutritional deficiencies and imbalances
List four examples of reversible cell injury
Hydropic change
Lipidosis
Glycogen accumulation
Neuronal chromatolysis
What are the cellular characteristics of reversible cell injury?
Generalised cell swelling
Blebbing of the plasma membrane
Chromatin condensing
What is hydropic change?
Acute cellular swelling caused by a failure of energy-dependent ion transport pumps which cause an electrolyte imbalance and thus a water overload
On gross examination, how to organs with hydropic change appear?
Enlarged
Pale
Turgid
On microscopic examination, how to cells with hydropic change appear?
Pale cytoplasm
Vacuolated cytoplasm
‘ballooning degradation’ (clear cytoplasm) in severe cases
What is lipidosis?
An abnormal metabolism of lipids
What can cause lipidosis?
Increased mobilisation of lipid stores
Nutritional disorders
Endocrine diseases
In which specific cells types is lipidosis more likely to occur?
Hepatocytes
Myocardial cells
Renal tubule cells
On gross examination, how to organs with lipidosis appear?
Enlarged
Pale/yellow
Soft
Greasy
On microscopic examination, how to cells with macrovesticular lipidosis appear?
Single round vacuoles in the cytoplasm causing peripheral displacement of the nucleus
On microscopic examination, how do cells with microvesticular lipidosis appear?
Multiple small round vacuoles in the cytoplasm with no peripheral displacement of the nucleus
- indicates more severe lipidosis
What are some causes of glycogen accumulation?
- Diabetes mellitus
- Glycogen storage disease
What are some specific causes of hepatic glycogen accumulation?
“Steroid hepatopathy’ (prolonged
corticosteroid/glucocorticoid treatment)
Hyperadrenocorticism
What is the gross appearance of the liver in a glucocorticoid (steroid) hepatopathy?
Enlarged
Pale brown to tan
Firm
Non-greasy
What is neuronal chromatolysis?
The chromatolysis of neuronal ganglia caused by autonomic nervous system disorders
Give an example of a disease caused by neuronal chromatolysis?
Equine dysautonomia (equine grass sickness)
What are the cellular characteristics of irreversible cell injury?
Severe endoplasmic reticulum and mitochondrial swelling
Lysosome rupturing
Blebbing of the plasma membrane followed by membrane rupturing
Nuclear membrane rupture and chromatin fragmentation
Which ion is found in the cytoplasm of cells undergoing irreversible cell injury?
Increased cytoplasmic Ca2+
What causes oxidative stress in cells?
Free radicals/reactive oxygen species
List how free radicals/reactive oxygen species are produced in cells
Normal metabolic functions
Absorption of radiation
Activated leukocytes due to inflammation
Iron and copper catalysing the formation of free radicals
Nitrogen oxide
What are the two main mechanisms of cells death?
Apoptosis
Necrosis
What is hypoxia?
Partial oxygen deficiency to the cells/tissues
What is anoxia?
Complete oxygen deficiency to the cells/tissues
What are the possible causes of hypoxia?
Heart failure
Respiratory failure
Ischaemia
Anaemia
Blockage of cell respiratory enzymes
What is ischaemia?
Partial reduction or complete loss of blood supply caused by local impairment of blood flow
What are the possible causes of Ischaemia?
Thrombosis
Mechanical interference with blood flow
What occurs within cells affected by ischaemia?
Ischaemia leads to a lack of oxygen in the mitochondria, decreasing oxidative phosphorylation and thus there will be a lack of ATP production. This causes a decrease in the actions of the Na+/K+ ATPase pump, an increase in anaerobic glycolysis and the detachment of ribosomes from the endoplasmic reticulum
How does a decrease in the actions of the Na+/K+ ATPase pump due to ischaemia affect a cell?
Leads to cellular swelling and membrane blebbing
How does increased anaerobic glycolysis due to ischaemia affect a cell?
The production of lactic acid decreases the cellular pH causing the clumping of chromatin
How does ribosome detachment from the endoplasmic reticulum due to ischaemia affect the cell?
Results in reduced protein synthesis and increased lipid deposition
What is infarction?
Necrosis due to ischaemia
What can happen if ischaemic tissue is restored with a blood supply?
This can result in ischaemia-reperfusion injury which is the paradoxical exacerbation of cell injury due to increased reactive oxygen species, the influx of inflammatory cells and the activation of complement
List the morphological changes seen in necrotic cells
Eosinophilia
Nuclear shrinkage
Fragmentation
Dissolution
List the morphological changes seen in apoptotic cells
Chromatin condensation
Formation of apoptotic bodies
List the five different types necrosis
Coagulative necrosis
Liquifactive necrosis
Caseous necrosis
Gangrenous necrosis
Enzymatic necrosis
Where in the body is coagulative necrosis seen?
Liver
Heart
Kidney
Skeletal muscle
What does it mean when necrotic cells become ‘individualised’?
The cells lose adherence to their basement membranes and adjacent cells
What is a characteristic cytoplasmic change in cells undergoing early stage necrosis?
Increased eosinophilia due to a loss of RNA (which is responsible for cytoplasmic basophilia)
What is a characteristic cytoplasmic change in cells undergoing late stage necrosis?
Rupture of the cells membrane causes the release of cellular contents into the extracellular space
What are the four possible nuclear changes seen in cells undergoing necrosis?
Pyknosis
Karyorrhexis
Karyolysis
Absence
Describe pyknosis
Nucleus becomes sunken, dark, homogenous and round
Describe karyorrhexis
Nuclear membrane ruptures and dark nuclear remnants are released into the cytoplasm
Describe karyolysis
Nucleus becomes pale due to chromatic dissolution by DNAses
Describe absence
Nucleus is completely dissolved or lysed
What are the possible causes of coagulative necrosis?
Hypoxia
Infarction
Bacterial toxins
Chemical toxins
Give examples of nephrotoxins which can cause renal tubular degradation and coagulative necrosis
Plants differing between species
Heavy metals (mercury, lead)
Chemicals (ethylene glycol)
Therapeutic drugs (antibiotics and chemotherapeutics)
How does ingestion of ethylene glycol cause acute renal tubular coagulative necrosis?
- When ethylene glycol is ingested, it is metabolised by the liver into glycoxylate which causes renal tubular epithelial degradation
- Glycoxylate is converted into oxylate which causes oxylate crystal deposition in the renal tubules, leading to tubule obstruction, mechanical damage and necrosis
Give three examples of viral infections which can cause coagulative necrosis
Infectious bovine rhinotracheitis
Canine parvovirus enteritis
Canine infectious hepatitis
Which virus causes infectious bovine rhinotracheitis?
Bovine herpes 1
Which virus causes canine parvovirus enteritis?
Canine parvovirus 2
Which virus causes canine infectious hepatitis?
Canine adenovirus 1
What are the clinical consequences of infectious bovine rhinotracheitis?
Thick plaques of fibronecrotic exudate covering the laryngeal and tracheal mucosa contributed by secondary bacteria
What are the clinical consequences of canine parvovirus enteritis?
Segmental necrosis and haemorrhage of the intestine
What are the clinical consequences of canine infectious hepatitis?
Friable, enlarged liver with fibrin on the capsular surface
Oedema of the gallbladder
Describe the gross appearance of caseous necrosis
Dead tissue converted into a granular, friable mass (resembling cottage cheese)
Dystrophic calcification seen in the centre of the lesions
Describe the microscopic appearance of caseous necrosis
Accumulation of lysed cells
No tissue architecture
What is a classic cause of caseous necrosis?
Tuberculosis
What is an example of caseous necrosis seen in sheep and goats?
Caseous Lymphadenitis (CLA)
Which bacteria causes Caseous Lymphadenitis (CLA) in sheep and goats?
Corynebacterium Pseudotuberculosis
Describe the routes of infectious of corynebacterium pseudotuberculosis causing caseous lymphadenitis
Caused by arthropod bites or contaminated drips and bacterial spread via ruptured abscesses and oral/nasal secretions
What is the incubation time for corynebacterium pseudotuberculosis?
3 months
How does caseous lymphadenitis have a significant economic impact?
Due to carcase condemnation
Where in the body does liquefactive necrosis most commonly target?
The central nervous system
What causes liquefactive necrosis in the central nervous system?
Hypoxic or toxic neural necrosis
What occurs during liquefactive necrosis of the central nervous system?
Enzymatic dissolution of the neuropil and due to the little connective tissue in the central nervous system, the cavity is filled with fluid and debris
Give an example of a common disease which causes liquefactive necrosis
Polioencephalomalacia caused by bovine thiamine deficiency
What causes liquefactive necrosis in tissues outside the central nervous system?
Pyogenic bacteria infection causing the formation of an abscess
What are the three types of gangrenous necrosis?
Moist gangrene
Dry gangrene
Gaseous gangrene
Describe how moist gangrene occurs
Initial coagulative necrosis followed by infarction and the active action of saprophytic bacteria
Describe the gross examination of moist gangrene
Soft, moist, reddish-brown tissue with a putrid smell and sometimes gas bubbles
Describe how dry gangrene occurs
Coagulative necrosis secondary to infarction with mummification (dehydration)
Where in the body is dry gangrene most commonly seen?
In the extremities i.e. distal limbs, tail, ears, udders
List some possible causes of dry gangrene
Toxin ingestion
Frostbite
Describe the gross examination of dry gangrene
Shrivelled, dry, black/brown tissue
What is the other name used to describe gas gangrene
Malignant oedema
Describe how gas gangrene occurs
Anaerobic bacteria infiltrates the body via a penetrating wound or via ingestion, proliferates and produces toxins causing gas gangrene
Describe the gross appearance of gas gangrene
Dark red/black semi-haemorrhagic exudate tissue, gas bubbles and coagulative necrosis of the muscle
Give an example of anaerobic bacteria that can cause gas gangrene
Clostridium Chauvoei (blackleg)
What are three ways fat necrosis can occur?
Enzymatically via pancreatitis
Traumatically via crushed fat around the pelvis after dystocia or crushed sternal fat in recumbent animals
Idiopathic
What is dystocia?
A difficult birth
List three possible consequences of necrosis
Inflammatory reactions in viable tissue
Digestion and liquefaction of necrotic tissue
Regeneration of normal tissue or fibrous scarring
What are the two main causes of apoptosis?
- Physiological
- Pathological
What are the two main apoptotic pathways?
- Intracellular (mitochondrial)
- Extracellular (death receptors)
What are cellular accumulations?
Degenerative changes caused by metabolic alterations
What are some examples of intracellular accumulations?
- Excessive normal cellular components (e.g lipids, proteins, water, carbohydrates)
- Abnormal exogenous or endogenous substances
- Pigments
What are some examples of extracellular accumulations?
- Amyloid
- Calcification
- Urates
What are some of the causes of intracellular accumulations?
- Increased rate of metabolism of endogenous substances
- Genetic or acquired defects in metabolism, packaging, transport or secretion of substrates
- Failure of enzymatic machinery to degrade or transport abnormal exogenous substances
Give an example of intracellular exogenous accumulation
Lipofuscin
In which types of cell/tissues does lipofuscin occur?
- Stable cells/tissues
- Permanent cells/tissues
Give an example of intracellular endogenous accumulation
Haemosiderin
What is haemosiderin?
A form of storage iron derived from the breakdown of erythrocytes
In which organs does hemosiderin most commonly accumulate?
Organs involved in erythrocyte degradation (liver, spleen)
How is haemosiderin accumulation presented both grossly and microscopically?
Golden yellow or brown pigmentation
What is local haemosiderin accumulation associated with?
Bruising
What is generalised haemosiderin accumulation associated with?
Haemolytic anaemia and/or haemochromatosis
Which stain is used to identify haemosiderin accumulation?
Perls blue stain due to the iron content in haemosiderin
Give three examples of extracellular accumulations
- Amyloid
- Calcification/mineralisation
- Gout
What are amyloids?
Extracellular proteinaceous material consisting of a diverse group of beta sheet glycoproteins
Why can amyloids accumulate so easily?
Amyloid is resistant to normal proteolytic mechanisms so can easily accumulate and cause cell/tissue compression
List some of the clinical consequences of amyloid accumulation (amyloidosis)
- Atrophy
- Cell death (necrosis/apoptosis)
Which stain should be used to identify amyloid accumulation?
Congo red
Which kind of amyloidosis is the most common in animals?
Secondary (relative systemic) amyloidosis
Describe what causes secondary (relative systemic) amyloidosis
The sustained production of the lipoprotein, serum amyloid A (SAA), by the liver in response to chronic inflammation and/or necrosis
Where in the body is secondary (relative systemic) amyloidosis commonly seen?
- Kidneys
- Liver
- Spleen
- Lymph nodes
What can cause primary amyloidosis?
- Plasma cell tumours (VERY RARE IN ANIMALS)
- Seen in the islet cells of cats with type two diabetes mellitus
What is the gross appearance of kidneys with renal amyloidosis?
- Waxy
- Enlarged
- Pale
- Swollen cortex
What is calcification?
Calcium deposition in necrotic or normal tissue
What are the two types of calcification?
- Dystrophic
- Metastatic
What is dystrophic calcification associated with?
Necrotic tissues - most commonly in coagulative, caseous and fat necrosis
Why do necrotic cells/tissues undergo calcification?
Dead/dying cells cannot regulate cytoplasmic calcium influx so the calcium accumulates in the mitochondria
What is metastatic calcification associated with?
Normal tissues secondary to hypercalcaemia
What are the five common causes of metastatic calcification?
- Renal failure
- Vitamin D toxicosis
- Hyperparathyroidism (primary or secondary)
- Paraneoplastic hypercalcaemia
- Destruction of bone from primary or metastatic neoplasms
Which stain should be used to identify mineralisation/calcification deposits?
Von Cossa staining
What is gout?
Gout is deposition of sodium urate crystals (Tophi)
Why is gout only seen in birds and reptiles?
As birds and reptiles excrete uric acid as semi-solid urates
What are the two different types of gout?
- Articular gout
- Visceral gout
List three possible causes of visceral gout
- Vitamin A deficiency
- High protein diet
- Renal injury
Describe the gross examination of gout
Grey/white granular deposits on the visceral serosa
Describe the microscopic examination of gout
Radial deposits surrounded by inflammation and fibrosis
