Inflammation and cell injury Flashcards
when cells encounter stress, what do they attempt to do?
adapt in order to maintain normal function and viability.
what does cell adaptation include?
Adaptations can include changes in size (atrophy or hypertrophy), number (hyperplasia), form (metaplasia), or function (increased or decreased activity).
If the stress is too severe or persists for too long, and the adaptive capacity is exceeded, what happens to the cell?
it’s injured
as it relates to cell injury, what’s the difference between reversible and irreversible injury?
In reversible injury, the changes the cell undergoes are not permanent, and the cell can recover if the stress is removed.
When the damage is too severe or persistent, it leads to irreversible injury, resulting in cell death.
what does reversible injury involve?
This might involve swelling, loss of microvilli, mitochondrial changes, and dilation of the endoplasmic reticulum, but the cell remains alive and can potentially return to its normal state.
what does irreversible injury involve?
This can occur through two primary pathways:
Apoptosis: Programmed cell death characterized by cell shrinkage, chromatin condensation, and DNA fragmentation. Apoptosis is often a controlled process that allows the body to remove cells that are no longer needed or are a threat to the organism without causing an inflammatory response.
Necrosis: Unregulated cell death due to overwhelming damage. It is characterized by swelling, rupture of the cell membrane, and subsequent inflammation. Necrosis often results from factors such as toxins, infections, or ischemia (lack of blood supply).
what is the difference between apoptosis and necrosis?
Apoptosis: Programmed cell death characterized by cell shrinkage, chromatin condensation, and DNA fragmentation.
Necrosis: Unregulated cell death due to overwhelming damage. It is characterized by swelling, rupture of the cell membrane, and subsequent inflammation.
what are the causes of cell injury?
Hypoxia (decreased oxygen): When cells don’t receive enough oxygen, they cannot produce sufficient ATP by aerobic respiration. This energy deficit compromises essential energy-dependent functions, leading to cellular damage.
Ischemia (decreased blood flow): Ischemia not only deprives cells of oxygen but also impedes the delivery of nutrients and the removal of metabolic wastes. It’s more harmful than hypoxia alone because it affects the supply of substrates for glycolysis.
Physical and Chemical Agents:
Trauma: Physical impact can cause direct damage to cell structures.
Burns: Thermal damage can denature proteins and disrupt cell membranes.
Radiation: Can cause ionization of molecules within cells, leading to molecular damage, particularly to DNA.
Toxins: Chemicals can interfere with biochemical pathways, leading to cell dysfunction and death.
Infectious Agents: Bacteria, viruses, fungi, and parasites can all cause cell injury. They can directly damage cells, produce toxins, or induce damaging immune responses.
Metabolic Abnormalities: Both genetic disorders (such as inborn errors of metabolism) and acquired conditions (like diabetes) can lead to accumulations of toxic substances or deficiencies in critical enzymes.
Immune Dysfunction:
Hypersensitivity Reactions: Exaggerated immune responses can cause collateral tissue damage.
Autoimmune Diseases: The immune system mistakenly attacks the body’s own cells.
Nutritional Imbalances: Deficiencies or excesses of nutrients can cause cellular damage. For example, vitamin deficiencies can impair cellular functions, while excess glucose can lead to hyperglycemia and associated cellular injuries.
Aging: Over time, cells accumulate damage and lose their ability to function properly. The repair mechanisms become less efficient, and cells may enter senescence (a non-dividing state) or die.
as it relates to mechanism of cell injury, what does ATP depletion leads to?
(1) reduced Na+/K+ ATPase activity causing cellular and endoplasmic reticulum swelling.; (2) Shift to anaerobic glycolysis (to produce energy) which leads to glycogen depletion and increased lactic acid (low intracellular pH which can denature protein); (3) Reduced calcium pump activity which alters calcium homeostasis and activates enzymes like proteases etc; (4) Reduced protein synthesis due to reduced energy.
what results from hypoxia, reactive oxygen species (ROS), and ↑ intracellular calcium levels and leads to increased mitochondrial permeability which causes impaired oxidative phosphorylation resulting in production of ROS (damages lipids, proteins, and nucleic acid) and leakage of apoptotic proteins (e.g., cytochrome C and caspases) into the cellular cytoplasm?
Mitochondrial damage
DNA damage that is irreversible results in what?
apoptosis (apoptosis can also result in excess of misfolded proteins).
Apoptosis is characterized by cell shrinkage, chromatin condensation, and DNA fragmentation.
what is hyperplasia (physiologic hyperplasia)?
increase in number of cells able to undergo mitosis which often leads to increase in organ size
Terminally differentiated cells, such as cardiac muscle cells (myocytes) and neurons, do not divide in adults and therefore do not undergo hyperplasia. Instead, these cells may respond to stress through hypertrophy, where the individual cells increase in size rather than number.
what are 3 forms of physiologic hyperplasia and what do they involve?
Hormonal Hyperplasia: Such as the enlargement of the breasts during pregnancy due to hormonal changes which stimulate the mammary glands to prepare for lactation.
Compensatory Hyperplasia: Such as the regeneration of the liver following partial hepatectomy. The remaining liver tissue grows to compensate for the lost tissue, thanks to the liver’s unique ability to regenerate.
Endometrial Hyperplasia: Occurring in the menstrual cycle, where the endometrium (lining of the uterus) thickens in preparation for potential implantation of an embryo.
what is pathological hyperplasia?
hyperplasia from abnormal stimuli sometimes preceding cancerous growth
what are 2 forms of pathological hyperplasia and what do they involve?
Examples include:
Adrenal Hyperplasia: The adrenal glands may enlarge due to the excess production of adrenocorticotropic hormone (ACTH), which can be caused by a pituitary adenoma (a benign tumor of the pituitary gland).
Endometrial Hyperplasia: This can occur due to prolonged exposure to estrogen without adequate progesterone balance, leading to an overgrowth of the lining of the uterus.
which type of cells don’t undergo hyperplasia?
myocytes and neurons because they can’t undergo mitosis.
Terminally differentiated cells, such as cardiac muscle cells (myocytes) and neurons, do not divide in adults and therefore do not undergo hyperplasia. Instead, these cells may respond to stress through hypertrophy, where the individual cells increase in size rather than number.
what is hypertrophy?
Individual cells increasing in size instead of numbers and normally causing organs to enlarge.
what’s an example of physiological hypertrophy?
For example, when you exercise, your skeletal muscles undergo hypertrophy as the muscle fibers increase in size due to the enhanced demand for strength and endurance. This type of hypertrophy is generally considered healthy and reversible.
what is pathological hypertrophy?
hypertrophy as an adaptation to abnormal conditions
what’s an example of pathological hypertrophy?
Cardiac Hypertrophy: The heart muscle (myocardium) can increase in size in response to conditions like aortic stenosis (where the heart has to pump harder to push blood through a narrowed aortic valve) or chronic hypertension (high blood pressure that makes the heart work harder to circulate blood). This type of hypertrophy is often a maladaptive response and can lead to adverse cardiovascular events.
how can you distinguish between hyperplasia and hypertrophy when they both look the same with the naked eye?
to determine whether the size change is due to hypertrophy (increase in cell size) or hyperplasia (increase in cell number), microscopic examination is needed. This examination allows for the observation of individual cells and their components, providing insight into the underlying mechanisms of the increase in organ size.
how does the induction of hyperplasia begin and what does it entail?
Pathogenesis of hyperplasia: The induction of hyperplasia often begins with the upregulation of receptors on the surface of cells. This upregulation can be due to increased levels of hormones or growth factors that bind to these receptors. Once activated, these receptors initiate signaling pathways that lead to the expression of genes involved in cell division.
Induced Proteins: These genes often code for transcription factors that activate other genes necessary for cell cycle progression. Additionally, proteins that promote cellular growth and division, such as enzymes involved in DNA replication, may be upregulated.
how does the induction of hypertrophy begin and what does it entail?
Pathogenesis of Hypertrophy: It involves the induction of protein synthesis within individual cells, leading to increased cellular components. This can result from mechanical stress, as seen in muscle cells during exercise, or hormonal stimulation.
Induced Proteins: In response to such stimulation, cells increase the production of structural proteins, such as contractile proteins in muscle (e.g., actin and myosin), and enzymes that generate energy for the cells. There may also be an induction of embryonic proteins, which are proteins expressed during the growth and development of the organism but are also re-expressed during regenerative processes or in response to injury.
what are examples of induced proteins?
transcription factors, contractile proteins, and embryonic proteins.
what’s the difference between atrophy and hypoplasia?
Atrophy occurs in a once normally developed organ.
If organ did not develop normally (was never of normal size), it’s called hypoplasia [aka underdevelopment].
what type of epithelium lines the esophagus and what epithelium does it change to during metaplasia due to barretts esophagus?
from stratified squamous to columnar
what is barret’s esophagus?
Normal Condition: The normal lining of the esophagus is composed of squamous epithelium.
Abnormal Condition: With chronic reflux of stomach acid (gastroesophageal reflux disease, GERD), the squamous epithelium can be damaged.
Metaplastic Change: To protect against the acid, the squamous epithelium may change into columnar epithelium, which is better able to handle the acidic environment. This condition is known as Barrett esophagus and can increase the risk of esophageal cancer.
what epithelium does the bronchial tubes have and what does it change to during metaplasia?
Normal Condition: The normal lining of the bronchial tubes of the lungs is composed of columnar ciliated epithelial cells.
Abnormal Condition: Chronic exposure to irritants like cigarette smoke can damage these cells.
Metaplastic Change: The body may replace the normal columnar cells with squamous epithelial cells, which are more resistant to the irritants but do not function the same as the original cells, as squamous cells do not have cilia to move mucus.
what type of tissue does metaplasia lead to which can also precede cancer?
dysplasia
severe form of cellular abnormality that can precede cancer.
what is metaplasia?
a reversible change where one type of cell changes to another to better withstand an adverse environment
what will dysplasia in esophagus develop into if left untreated?
esophageal adenocarcinoma, a type of cancer.
what is liquefactive necrosis?
occurs in soft organs that lack a protein-rich matrix with high enzymatic content (pancreas) or in lipid-rich organs (brain).(allowing lysis of cells and surrounding proteins). Enzymatic breakdown more prominent than protein denaturation.
what is coagulative necrosis?
occurs in solid organs (allows preservation of shape by coagulation of proteins). Protein denaturation is more prominent than enzymatic breakdown. May occur in any organ (heart, liver, kidney). In brain is rapidly followed by liquefactive necrosis.
what is the most common type of necrosis?
coagulative necrosis
This is the most common type of necrosis, typically seen after ischemic events (like a heart attack). The architecture of dead tissues is preserved for a couple of days.
what is fat necrosis?
change in adipose tissue due to release of enzymes (lipases) from adjacent organs (pancreatitis). Released fatty acids combine with calcium to form “chalky” deposits (saponification).
what is caseous necrosis?
is a “cheesy-looking” necrosis associated with tuberculosis and other granulomatous disease processes.
what is fibrinoid?
results from fibrin leaking form blood vessels (in blood vessels or pericardium).
what type of infarct is hemorrhagic due to the re-entry of blood into the tissue following cell death.
Associated with
Loose tissues with collaterals such as liver (portal and systemic), lungs (pulmonary and bronchial), intestine (portal and systemic).
Lysis of an embolus that initially obstructed blood flow?
Red infarct
what type of infarct is due to continued inability of blood to re-enter the infarcted area.
Associated with
Solid tissues with single blood supply such as heart, kidney, spleen.
Atherosclerotic thrombi that cannot be lysed due to continued reformation at site of obstruction?
Pale infarct
which type of infarct involves Solid tissues with single blood supply such as heart, kidney, spleen? red or pale?
pale infarct
which type of infarct involves Loose tissues with collaterals such as liver (portal and systemic), lungs (pulmonary and bronchial), intestine (portal and systemic)? red or pale
red infarct
what is a product of lipid peroxidation, which accumulates in lysosomes as the cell ages. The cell cannot rid itself of these lipofuscin-laden lysosomes (aka, brown atrophy).
Affects heart and liver?
Lipofuscin
what is metastatic calcium?
hypercalcemia leads to deposition of calcium within normal or abnormal tissue.
what is dystrophic calcium?
Patients with normal calcium levels have deposition only within abnormal tissue (i.e., necrotic tissue).
Affects vasculature, kidneys, and lungs.
what is Accumulation of iron in organs with no clinical effects. The iron pigment is frequently within macrophages?
Hemosiderosis
what is Accumulation of iron in parenchymal cells resulting in side effects (congestive heart failure, diabetes mellitus, and cirrhosis).
Affects liver, skin, pancreas, and heart?
Hemochromatosis
more severe than hemosiderosis and cause tissue damage
