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Tissue/Organ injury and death
Terms in this set (100)
Overall process of Cell's Adaptation to Injury / Stress
Each various types of differentiated cells within our body is structurally/ physiologically unique as a result of ___________________
programmed expression or suppression of gene transcription + translation of genome
List example Etiologies of cell stress/ injury:
-chemical agents (drugs)
-Inflammatory / Immune reaction
-Genetic and epigenetic lesions
-Aging / Senescence
Overview of Cell adaptation and Injury
Normal cells try to adapt to the stress. If the injured cells are under control and the stress is not too toxic, they will reverse themselves back to normal. -->
However, if the injury/ stress stimulant is prolonged & sustained, cells become irreversibly damaged that can lead to either necrosis or apoptosis --> "Irreversible injury"
What are 5 mechanisms of Adaptation by Injured cells?
dec. in SIZE
inc. in SIZE
inc. in cell #
change of one type of epithelial cell to another type of epithelial cell
pleomorphism and losing cell uniformity
Cell atrophy occurs due to :
reductions in intracellular organelles by Autophagy
(e.g. mitochondria, smooth/rough ER, granules, cytoskeleton, etc)
Tissue and organ atrophy occurs due to:
CELL atrophy & decrease in cell numbers as a consequence of cell death by necrosis or apoptosis.
List all Initiating factors of cell ATROPHY :
-Decreases in workload
-Loss of innervation
-Diminished blood supply
-Loss of growth factor or endocrine stimulation
-Aging, senescence, death
Poliomyelitis cause Which type of cell adaptation mechanism?
Skeletal muscle atrophy
(due to loss of innervation)
-infection and destruction of anterior horn motor neurons of the spinal cord, leading to loss of innervation --> Muscle atrophy
Atherosclerosis in kidney cause which type of cell adaptation mechanism?
Atrophy of kidney
(due to chronic reduction in blood supply)
-Deposition of plaques of fatty deposits build up on the inner walls of arteries --> chronic reduction in blood supply --> Kidney ATROPHY.
atheroma= fatty deposits causing degeneration of arterial walls
Alzheimer disease cause Which type of cell adaptation mechanism?
(due to loss/death of neurons)
Are ALL cell/tissue Atrophies reversible?
No; depends on cell type.
Muscle cells atrophy is reversible, whereas Neurons atrophy is irreversible (b/c they do not undergo replication)
What causes Thymus atrophy?
Cell hypertrophy occurs due to :
Increases in intracellular organelles
(mitochondria, smooth/rough ER, cytoskeleton, etc)
Tissue and organ hypertrophy occurs due to:
CELL hypertrophy and increases in cell numbers
(Cell hypertrophy leads to tissue/organ hypertrophy)
List all causes of Cell Hypertrophy:
-increased hormonal stimulation
-Increased functional demand
-Increased functional demand
What is a Gravid?
Gravid uterus refers to a pregnant uterus that is carrying a developing egg
What are 2 example of tissues/organs that undergo both Hypertrophy and Hyperplasia at the same time?
-Gravid uterus during pregnancy (smooth muscle cells)
-Breast enlargement during pregnancy
What types of cell adaptation mechanisms can be seen in Gravid uterus?
-Hypertrophy + Hyperplasia
(due to hormonal change during pregnancy)
Before/ during pregnancy, breast undergoes ________________ in preparation for lactation
Hyperplasia + Hypertrophy
Muscle cells can undergo (Hyperplasia/ Hypertrophy/ both)
(the Muscle cell numbers remain unchanged)
List all example scenarios of Tissue/Organ Hypertrophy:
-Pregnancy, causing Endometrium& myometrium hypertrophy in Gravid uterus
-increased workload (e.g. lifting weights, increased demand for detoxification in liver)
<Pathological increase in functional demand>
-Heart ventricle hypertrophy, due to sustained HBP
What adaptation mechanism do hepatocytes undergo when there's in increase in demand for detoxification of certain drugs?
-->leading to liver hypertrophy
Which cell adaptation mechanism does Heart ventricle muscle undergo as a result of sustained BP > 140/90?
Hypertrophy of myocardial cells.
(increased thickness of ventricle wall --> difficult pumping of blood --> even more hypertrophy of walls b/c of increased function)
4 cell classifications in terms of proliferative capacity:
don't worry about def'n for this one
-Permanent cells: cannot divide
-Stable cells: In G0 (quiescent) but may enter G1
-Labile cells: continuously cycling
-Stem cells: pluripotent progenitors
***define permanent cells
***define labile cells
***define stem cells
pluripotent progenitor cells
Give examples of Permanent, non-dividing cells:
***Give examples of Labile cells:
-Squamous epithelium cells
-Bone marrow cells
***_________________ are types of cells that are normally NOT in cell cycle, but with signals (e.g. growth factors + protooncogenes) can be signaled & stimulated to enter the cell cycle.
Quiescent Stable cells
***Give an example of Quiescent stable cells:
Hepatocytes (liver cells)
Cell hyperplasia occurs due to :
-regulated, enhanced hormonal or growth factor stimulation of labile or stable cells keeping them in cell cycle
--> Enhanced cell division
What is the consequence of withdrawing hormone or growth factor in cells undergoing Hyperplasia?
-Arrest cell division
-often leads to cell death by apoptosis (in order to go back to original # cells)
What is the consequence of Excessive or prolonged cell hyperplasia ?
Development of Neoplasia
abnormal, irreversible, autonomous increase in cell division as a result of genetic or epigenetic dysregulation of cell cycle
***hyperplasia vs neoplasia
List example scenarios of Hyperplasia:
-Endometrial hyperplasia due to increased Estrogen level
-Hormonal breast hyperplasia
What cell adaptation mechanism does Endometrium undergo in response to Elevation of estrogen? inc in what specifically?
--> increased number of ducts
change of one type of epithelial cell to another type of epithelial cell
Explain how Metaplasia occurs in respiratory epithelium as a result of smoking:
Normal= ciliated columnar epithelium
--> These cells die because they're sensitive to smoking and other noxious stimulants. Basal cells try to replace these cells by differentiating, but instead of becoming ciliated columnar epithelium, it differentiates into stratified squamous epithelium --> squamous Metaplasia
Example scenarios of Metaplasia:
-Squamous metaplasia of respiratory epithelium due to cigarette smoking
-Replacement of Esophageal squamous epithelial mucosa w/ intestinal epithelial mucosa secondary to GERD.
What adaptation mechanism does Esophagus undergo in response to GERD?
Normally Esophagus is lined by stratified squamous cells that are resistant to acid, but undergoes metaplasia to be replaced by Intestinal epithelial cells (Columnar cells)
-Pleomorphism (variation in size and shape)
-Loss of cell uniformity, architecture, and orientation
(can progress to neoplasia, but not always)
Dysplasia histologic features:
-relates principally to metaplastic epithelium: skin, respiratory & GI tract.
-Hyperchromatic nuclei (darker nucleus)
-increase in mitotic figures
Describe sequence of events that occur in smoker's respiratory epithelium, leading to bronchogenic squamous cell carcinoma:
1. Normal (ciliated columnar)
2. Squamous metaplasia
4. Invasive carcinoma
--> invade normal tissue/organ
Which of the following processes are Reversible?
-Hypertrophy / Hyperplasia
ALL of them are reversible, EXCEPT Neoplasia
When does the Reversible injury become Irreversible injury?
When the stress/injury prolongs, sustains, and becomes severe.
Pathophysiology of Cell injury:
(ALL cellular processes in response to irreversible + reversible damage)
-Free radical production
-Loss of Ca/Na/K Ion homeostasis
-Hydrolytic enzyme activation (phospholipases, proteases, nucleases)
-Loss of membrane integrity
Cell is no longer needed in the body --> Fragments into very small membrane-bound apoptotic bodies --> Eaten up by professional phagocytes --> Dead cells completely removed. (nothing to promote acute/ chronic inflammation, like in necrosis) **
Breakdown of plasma membrane --> Intracellular constituents digested & leaked --> Death by necrosis (Irreversible)
Cell remnants left behind --> induce acute & chronic inflammatory process
Explain the mechanism of REVERSIBLE injury that occurs as a result of Ischemia:
No oxygen available --> decreased oxidative phosphorylation --> less ATP production (required for Na/K ATPase) --> screwed up cell physiology & ion gradient --> Alterations in cells.
Deficient ATP will make the cell undergo anaerobic glycolysis, lactic acid production --> Cell acidosis & clumping of nuclear chromatin
other effects - detachment of ribosomes, decreased protein synthesis, lipid deposition
List all Cellular processes in REVERSIBLY DAMAGED CELLS:
-Cellular swelling & Bleb formation
-Disruption of Rough ER
-Clumping of nuclear chromatin
*** why do cells go through necrosis? (List all Cellular processes in Necrosis):
-Loss of mitochondrial integrity/function
-Disruption of lysosomes
-Degradation of DNA, RNA, proteins, lipids
-Plasma membrane damage
-Loss of ion & Water homeostasis
-Disintegration and rupture of cell
-Extracellular release of cytosolic constituents
-ACUTE & CHRONIC INFLAMMATION
Reversible Cell injury
Apoptosis and Necrosis are associated with (Reversible / Irreversible) Injury
Acute and chronic inflammation with Scar and Fibrosis is associated with (Necrosis/ Apoptosis/ Both)
Explain what a Necrotic cell looks like:
-Plasma membrane destroyed
-Mitochondria irreversibly damaged
Histopathologic difference in reversibly damaged vs. Irreversibly damaged Renal proximal tubule epithelial cells:
Reversibly damaged - Nucleus still present
Irreversibly damaged - Nucleus gone (hallmark)
Mechanism of Cell Necrosis
calcium levels inc. and activate hydrolytic enzymes, tearing the cell apart => PM destroyed
ALWAYS leads to acute & chronic inflammation --> can lead to fibrosis and scarring.
What is the response of Coronary arteries to Atherosclerosis?
Lipid deposition leads to development of acute & chronic inflammation of arteries --> Proliferation of CT --> lumen size significantly decreased in size
Endothelial cells also trigger release of coagulating factors in the lumen --> Prolonged & worsened decrease in blood flow --> completely occluded vessel ("Thrombic occlusion")
***Types of Necrosis:
FL G @ HCC
FLorida Guys at Hillsborough Community College
most likely to go through ischemia?
Which cells have low vs. Intermediate vs. High susceptibility to Ischemic necrosis?
Depending on cell TYPES, there's different clinical manifestations of cell death by necrosis
-triggered by Ischemia
-Identified Microscopically: outlines of cells but NO NUCLEI anywhere
-Dead tissue (karyolysis)
e.g. Atherosclerosis, ischemia, Renal infarct
________________ necrosis is a condition of cell death that is caused by lack of blood flow
-Purulence & Pus & Abscess
-commonly caused by bacterial infection
-Severe inflammatory process which release free radicals and enzymes that kill the tissue & digest the dead tissue.
--> No tissue left in the area except pus.
Liver abscess is an example of ______________ necrosis
(Liver abscess = pus-filled mass in the liver that can develop from injury or an intra-abdominal infection)
Hallmark of Coagulation necrosis:
-Surrounding the infarct area, there's purple granulocytes everywhere (bc of chronic inflammation)
-occurs in tissues with a lot of fat
-Formation of free radicals
-Inflammation causes free radicals release --> damage fat --> Fats become epoxides --> hydroperoxides --> Free radicals
e.g. kidney, pancreas, appendix
What type of Necrosis is typical of Pancreatitis ?
-LUNG: Indicative of TB infection
-Common in lung
-Caseous "cottage cheese" as necrosed tissue
Tuberculosis undergoes _____________ Necrosis in the lung
-Common cause: complete occlusion of artery
-Shutting off complete blood supply --> Inflammatory cells cannot enter --> Tissue mummifies
-Inflammatory process that cause injury & bleeding
-tissue damage prohibits deoxygenated, or venous, blood from leaving the organ, leading to the hemorrhage
Cell atrophy occurs due to reduction intracellular organelles done by process of _______________
Tissue/organ atrophy occurs due to _________________ by a process of _______________
Cell atrophy occurs due to reduction intracellular organelles done by process of autophagy
Tissue/organ atrophy occurs due to cellular atrophy or dec. in cell # by a process of necrosis + apoptosis
What cellular process causes the Cell hypertrophy, to increase in size?
INCREASES in number of intracellular organelles
Renal infarct is an example of _____________ Necrosis
(Renal infarct = cone-shaped, "white" ischemic area due to lack of hemorrhaging and limited red blood cells accumulation)
Cellular features of Apoptosis:
-Apoptotic body formation
-Phagocytosis of Apoptotic bodies
List all Etiologies of Apoptosis:
-Morphogenesis and metamorphosis
-Normal cell aging, senescence and death
-Hormone/growth factor withdrawal
-Mitochondrial cytochrome C release
-Failed DNA repair (G1)
-Cytotoxic drugs & ionizing radiation
-Immune (CD8 T-cells), NK cells, cytokines
Enzyme Caspases are involved in (apoptosis/Necrosis) pathway.
Function of Caspase in Apoptosis:
to cleave a peptide bond between cystein and aspartate
-also referred to as cystein-aspartate protease
Initiator caspases 9- initiate the apoptosis signal (other types include 9-12)
executioner caspases 3 - carry out the mass proteolysis that leads to apoptosis (other types including 3, 6, 7)
2 main functions of Executioner caspase that contribute to apoptosis:
1. Endonuclease activation --> leads to nuclear fragmentation
2. Breakdown of cytoskeleton
In response to cell injury, Mitochondria releases ________________ that initiate Apoptotic process.
2 pathways of Apoptosis:
'Death Receptor Pathway'
--> Most common mode of Apoptosis
Death receptor Pathway of Apoptosis involves expression of many _______________ receptors on cell surface.
(expressed by CD8+ T-cells)
(tumor necrosis factor)
-expressed by activated macrophages
Examples scenarios of our body undergoing Apoptosis as an essential part of development:
Cells that have undergone Hyperplasia reduce # cells back to normal by (Apoptosis/Necrosis)
List all diseases caused by Dysregulated Apoptosis: (inc./dec.)
-cancer (p53 mutation, Bcl-2 over expression)
-Inflammatory (PMN) tissue injury
-Viral induced lymphopenia (HIV, AIDS)
Bcl-2 over-expression results in _______________ cancer.
Explain why Menopause cause women to develop osteoporosis:
Before menopause, Estrogen normally modulates Apoptosis of osteoclasts. However, when menopause hits, Estrogen level is reduced--> Apoptotic regulation of osteoclasts inhibited --> Higher concentration of osteoclasts --> More bone resorption
Intrinsic Apoptosis pathway involves Cytochrome C activating _______________ enzyme for initiation of apoptosis
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