Flashcards in Cell Injury 1 Deck (19)
CELL MEMBRANE COMPONENTS?
Proteins- Pores/channels, transport, receptors, cell to cell and cell to matrix adhesion complexes.
TRANSMEMBRANE PROTIEN FUNCTIONS?
Cell surface receptor.
Attachment of cytoskeleton.
ROUGH ENDOPLASMIC RETICULUM
Critical site of protein synthesis.
Transport vesicles take newly synthesised proteins from the RER to the Golgi body apparatus, where they are packaged for secretion- Structural maturation and refinement.
Secretory vesicles then take the protein, now in it's final structural form, and transfer it from the cytoplasm to the cell membrane.
If a normal cell is put under stress, what happens?
An inability to adapt will result in cell injury.
If a normal cell is acted on by an injurious stimulus, what happens?
-If the stimulus is mild/transient, the injury will be REVERSIBLE, and the cell can reverse back to it's normal state.
-If the stimulus is sever/progressive, IRREVERSIBLE INJURY will occur.
This leads to cell death, either by apoptosis (programmed cell death) or necrosis.
CAUSES OF CELL INJURY
Oxygen deprivation (ischaemia, hypoxia)
Chemicals, toxins and drugs
CELL RESPONSE AND ADAPTATION VARIES FOR DIFFERENT CELL POPULATIONS
1. Labile cells
2. Quiescent cells- are capable of dividing if stimulated to do so.
3. Permanent cells- Non dividing, cannot be induced to divide.
Increased cell size.
Occurs in all three cell populations.
In cells that can replicate, hyperplasia will also contribute to increased size of organ.
Can be physiologic or pathologic:
PHYSIOLOGIC- Normal. Muscle hypertrophy due to increased workload eg. Larger muscles in draft horses.
Hormonal stimulation causes hypertrophy of reproductive organs eg. Uterine enlargement in pregnancy, mammary gland enlargement & activity in lactation.
INDUCTIONS OF HYPERTROPHY
1. Mechanical stretch (increased workload)
2. Agonists (eg. alpha-adrenergic hormones, angiotensin)
3. Growth factors (eg. IGF-1)
These cause signal transduction reulting in production of transcription factors. These factors then cause various effects:
1. Induction of embryonic/foetal genes (eg. cardiac alpha-actin, Atrial Natriuretic Peptide ANF/ANP)
2. Increased synthesis of contractile proteins
3. Increased production of growth factors.
These then cause INCREASED MECHANICAL PERFORMANCE.
Increase in cell number. In response to HORMONES and GROWTH FACTORS.
COMPENSATORY hyperplasia- Seen subsequent to tissue injury and loss. eg. Liver regeneration after damage.
MECHANISMS OF LIVER COMPENSATORY HYPERPLASIA
Response to liver loss:
INCREASED TRANSCRIPTION FACTORS, ANTIAPOPTOTIC FACTORS, DNA REPLICATION, CELLULAR PROLIFERATION.
CYSTIC ENDOMETRIAL HYPERPLASIA
Hormone induced. Caused by:
-Excessive and/or persistent oestrogenic stimulation.
-Persistent corpus luteum in the ovary- This produces progesterone, which in turn causes hyperplasia.
Cystic Endometrial Hyperplasia is a predisposing factor for pyometra.
Hormone induced, precise mechanisms unknown. Common in older intact dogs.
NOT seen in castrated dogs- removal of testes causes androgen removal -> prostate atrophy.
"Administration of oestrogens causes prostatic enlargement due to synergistic action of oestrogen and testosterone.
OESTROGEN causes MUSCULAR HYPERPLASIA
TESTOSTERONE causes EPITHELIAL HYPERPLASIA.
Thyroid gland hyperplasia, seen in foetuses due to maternal dietary iodine insufficiency.
Decreased organ/tissue size due to decreased cell size and number.
Can be PHYSIOLOGICAL or PATHOLOGICAL:
-PHYSIOLOGICAL- Common during normal development, aging and upon decrease of functional demand (possibly mediated by withdrawal of hormone situation)
eg. Embryological structures (notochord, thyroglossal duct), thymus, uterus, mammary gland.
PATHOLOGICAL- Depends on an underlying cause, can be localised or generalised.
-Decreased nutrient supply/starvation- Protein/energy malnutrition. Skeletal muscle is used as a source of energy, causing atrophy.
-Deficient blood supply, leading to tissue hypoxia.
-Decreased workload- Disuse atrophy. Seen in muscles if immobilised limbs eg. fractures.
-Denervation atrophy- Damage to motor neurones or axons causes rapid atrophy of muscle fibres.
-Pressure atrophy- An expansive lesion puts pressure on a tissue, impairing blood supply -> hypoxia/ischaemia -> atrophy.
eg. Tumour, fluid accumulation in brain ventricles.
-Loss of endocrine stimulation- eg. Prolonged corticosteroid therapy causes negative feedback on the HPA axis, decreasing ACTH production.
This decreases trophic stimulation of the adrenal glands, leading to adrenocortical atrophy.
A reversible change, where one DIFFERENTIATED cell type (epithelial or mesenchymal) is replaced with another cell type.
May be seen in cells that are sensitive to stress; they replace themselves with cells that are better adapted to deal with stress. ADAPTIVE SUBSTITUTION.
MOST COMMON EPITHELIAL METAPLASIA?
Columnar changes to squamous.
EXAMPLES/CAUSES OF METAPLASIA
1. CHRONIC IRRITATION- Particles and chemicals in lungs eg. smoke and other irritants, cause squamous metaplasia of cuboidal-columnar airway epithelium.
2. VITAMIN A DEFICIENCY- Causes squamous metaplasia of cuboidal/columnar epithelium in salivary gland ducts and of mucous glands in oesophageal mucosa.
3. OESTROGEN- Causes squamous metaplasia of urinary tract transitional epithelium and prostate epithelium.
4. CALCULI/STONES- In the lumen of salivary gland, biliary and pancreatic ducts. Mechanical injury from stones moving around causes chronic injury to epithelium, causing squamous metaplasia.
5. OSSEOUS METAPLASIA- In chronically injured soft tissues; turns to bone.
6. MYELOID METAPLASIA (EXTRAMEDULLARY HAEMATOPOEISIS)- Spleen and liver produce red blood cells, subsequent to bone marrow injury compromising haematopoeitic activity.