p.61
Mechanisms of Cell Injury
What occurs if necrotic cells and debris are not promptly destroyed?
They provide a nidus for the deposition of calcium salts and other minerals.
p.61
Pathologic Calcification
What is the term for the calcification that occurs in necrotic tissue?
Dystrophic calcification.
p.3
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the definition of pathology?
The study of disease, focusing on structural, biochemical, and functional changes in cells, tissues, and organs.
p.19
Adaptations of Cellular Growth and Differentiation
What does cellular adaptation refer to?
The process by which cells adjust to changes in their environment to maintain function.
p.5
Mechanisms of Cell Injury
What does pathogenesis refer to in a disease process?
The biochemical and molecular mechanisms of disease development.
What can potentially occur if the duration of injury is prolonged?
Irreversible injury and cell death.
What is a characteristic appearance of an apoptotic cell on histologic examination?
A round or oval mass of intensely eosinophilic cytoplasm with fragments of dense nuclear chromatin.
What occurs during Karyolysis?
The basophilia of the chromatin fades and there is a loss of DNA due to enzymatic degradation by endonucleases.
p.37
Mechanisms of Cell Injury
What is the relationship between the duration of injury and the outcome for cells?
A longer duration of injury increases the likelihood of irreversible injury and cell death.
p.80
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is a common trigger for apoptosis related to cellular environment?
Growth factor deprivation.
What happens during Karyorrhexis?
The pyknotic nucleus undergoes fragmentation.
p.100
Mechanisms of Cell Injury
What determines the consequences of cell injury?
The type, state, and adaptability of the injured cell.
What is the effect of the DNase being activated by executioner caspases?
It induces cleavage of DNA.
p.63
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
How are dead cells and their fragments handled during apoptosis?
They are rapidly devoured by phagocytes before leaking contents, preventing inflammation.
Does necroptosis involve caspase activation?
No, it is caspase-independent programmed cell death.
What happens to necrotic cells and their contents in a living patient?
They disappear due to enzymatic digestion and phagocytosis by leukocytes.
What triggers apoptosis in hormone-sensitive cells deprived of hormones?
The intrinsic (mitochondrial) pathway.
What process occurs to the fragments of apoptotic cells?
Phagocytosis of fragments.
p.100
Mechanisms of Cell Injury
What factors influence the cellular response to injurious stimuli?
The nature of the injury, its duration, and its severity.
p.42
Reversible Cell Injury
What can cause fatty change in cells?
Hypoxic injury, various forms of toxic or metabolic injury.
p.3
Overview of Cellular Responses to Stress and Noxious Stimuli
What techniques are used in pathology?
Molecular, microbiologic, immunologic, and morphologic techniques.
p.17
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
How does histopathology contribute to understanding diseases?
By examining tissue samples under a microscope to identify abnormalities.
p.7
Mechanisms of Cell Injury
What are examples of acquired causes of disease?
Infectious, nutritional, chemical, and physical factors.
p.45
Reversible Cell Injury
What are the ultrastructural changes of reversible cell injury?
Plasma membrane alterations, mitochondrial changes, dilation of the ER, and nuclear alterations.
p.59
Mechanisms of Cell Injury
What is formed at sites of lipid breakdown during fat necrosis?
Calcium soap (saponification).
p.38
Reversible Cell Injury
What are the characteristics of reversible cell injury?
Generalized swelling of the cell and organelles, blebbing of the plasma membrane, detachment of ribosomes from the ER, and clumping of nuclear chromatin.
What initiates the cascade of caspase activation in apoptosis?
The two initiating pathways converge.
p.37
Reversible Cell Injury
What characterizes the early stage of cell injury?
Cells may exhibit potentially reversible damage.
p.63
Mechanisms of Cell Injury
What do intrinsic enzymes do during apoptosis?
They degrade the cell's own nuclear DNA and nuclear and cytoplasmic proteins.
p.52
Mechanisms of Cell Injury
What texture do affected tissues exhibit in coagulative necrosis?
A firm texture due to denaturation of structural proteins and enzymes.
p.3
Overview of Cellular Responses to Stress and Noxious Stimuli
What does pathology aim to explain?
The signs and symptoms of diseases.
What is fibrinoid necrosis?
A special form of necrosis occurring in immune reactions involving blood vessels.
p.92
Mechanisms of Cell Injury
What role does TNF play in necroptosis?
It cross-links TNFR1, triggering downstream events.
What are executioner caspases responsible for?
They act on many cellular components, including cleaving an inhibitor of a cytoplasmic DNase.
What happens to the plasma membrane of apoptotic cells?
It remains intact but its structure is altered, making it a target for phagocytes.
p.59
Mechanisms of Cell Injury
What does fat necrosis involve?
Areas of white chalky deposits representing foci of fat necrosis.
p.5
Mechanisms of Cell Injury
What are morphologic changes in the context of disease?
The structural alterations in the cells and organs.
What are some conditions associated with increased apoptosis?
Neurodegenerative diseases, ischemic injury (myocardial infarction and stroke), and death of virus-infected cells.
p.76
Mechanisms of Cell Injury
What do the subsequent events after caspase-8 activation lead to?
Activation of multiple executioner caspases.
What are the features of cell shrinkage during apoptosis?
Formation of apoptotic bodies.
p.16
Overview of Cellular Responses to Stress and Noxious Stimuli
What is fine needle aspiration?
A minimally invasive procedure to obtain a sample of tissue or fluid.
What is apoptosis?
A normal phenomenon to eliminate no longer needed cells and maintain a steady number of various cell populations.
p.52
Mechanisms of Cell Injury
How are necrotic cells ultimately removed in coagulative necrosis?
By phagocytosis and digestion by lysosomal enzymes.
What is caseous necrosis most commonly associated with?
Foci of tuberculous infection.
What is the appearance of fibrinoid necrosis in H&E stains?
A bright pink and amorphous appearance.
p.7
Mechanisms of Cell Injury
What does multifactorial etiology imply?
It arises from the effects of various external triggers on a genetically susceptible individual.
p.69
Mechanisms of Cell Injury
What are caspases?
Cysteine proteases that cleave proteins after aspartic residues.
What contributes to the appearance of fibrinoid necrosis?
Deposits of immune complexes and fibrin that has leaked out of vessels.
What are apoptotic bodies?
Fragments formed from the breakdown of apoptotic cells, making them edible for phagocytes.
p.18
Overview of Cellular Responses to Stress and Noxious Stimuli
How are samples typically obtained for cytopathology?
Through fine needle aspiration, exfoliative cytology, or other sampling methods.
What change occurs to phosphatidylserine in apoptotic cells?
It flips from the inner leaflet to the outer layer of the membrane.
p.74
Mechanisms of Cell Injury
What is the role of anti-apoptotic proteins like BCL2?
They maintain the integrity of mitochondrial membranes and prevent leakage of mitochondrial proteins.
p.12
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What type of tissue sample is used for cytopathology?
Aspiration materials and exfoliative cytology (smear).
What are the three patterns of nuclear changes due to nonspecific breakdown of DNA?
Karyolysis, Pyknosis, and Karyorrhexis.
What is apoptosis?
A physiological event that removes unwanted, aged, or potentially harmful cells.
p.19
Overview of Cellular Responses to Stress and Noxious Stimuli
What are the three main cellular responses to stress and toxic insults?
Adaptation, injury, and death.
When does apoptosis occur?
During development and throughout adulthood.
What can low rates of apoptosis lead to?
Survival of abnormal cells, potentially resulting in cancer due to mutations in TP53 and defective DNA repair.
p.28
Adaptations of Cellular Growth and Differentiation
What do adaptations allow a cell to do?
Survive and continue to function by establishing new but altered steady states.
What role does apoptosis play in the body?
It serves to remove unwanted and potentially harmful cells.
What are some physiological situations where apoptosis occurs during embryogenesis?
Destruction of cells during implantation, organogenesis, developmental involution, and metamorphosis.
What is activated in response to growth factor deprivation that promotes apoptosis?
BIM and other pro-apoptotic members of the BCL2 family.
p.3
Overview of Cellular Responses to Stress and Noxious Stimuli
What role does pathology play between basic sciences and clinical medicine?
Pathology acts as a bridge between the basic sciences and clinical medicine.
p.19
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the significance of understanding cellular responses to stress?
It helps in diagnosing and treating diseases related to cell injury and death.
p.93
Mechanisms of Cell Injury
What is the role of caspase-1 in pyroptosis?
It cleaves a precursor form of IL-1 and releases its biologically active form.
p.33
Overview of Cellular Responses to Stress and Noxious Stimuli
What characterizes cell injury?
The cell is no longer able to adapt.
p.17
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the significance of identifying cell types in histopathology?
It helps in diagnosing diseases and determining treatment options.
p.36
Mechanisms of Cell Injury
What is the time lag between stress and morphologic changes in cell injury?
There is a time lag; changes may be seen in minutes to hours with histochemical techniques, and longer (hours to days) with light microscopy.
p.31
Mechanisms of Cell Injury
What leads to cell injury?
A sequence of events including exceeded adaptive responses, exposure to injurious agents or stress, and deprivation of essential nutrients.
p.1
Overview of Cellular Responses to Stress and Noxious Stimuli
Who is the professor for the Introduction to Medical Pathology course?
Prof. Dr. Aptullah HAHOLU.
What is the role of FasL on T cells?
It binds to Fas on the same or neighboring lymphocytes to induce apoptosis.
p.42
Reversible Cell Injury
What causes cellular swelling in reversible cell injury?
Incapable of maintaining ionic and fluid homeostasis due to failure of energy-dependent ion pumps in the plasma membrane.
p.76
Mechanisms of Cell Injury
What is the relationship between the extrinsic and intrinsic pathways of apoptosis?
They are interconnected and their combined activation delivers a fatal blow to the cells.
p.5
Mechanisms of Cell Injury
What is the first aspect of a disease process?
Etiology; the cause of the disease.
What can result from mutations affecting Fas or FasL?
Autoimmune diseases in humans and mice.
What is a pathological cause of apoptosis?
Elimination of damaged cells beyond repair.
What do cytotoxic T lymphocytes (CTLs) recognize?
Foreign antigens on the surface of infected host cells.
How does apoptosis affect inflammation?
It does not elicit inflammation, making it more difficult to detect histologically.
p.16
Overview of Cellular Responses to Stress and Noxious Stimuli
What is a PAP smear?
A test used to screen for cervical cancer by examining cells from the cervix.
p.72
Mechanisms of Cell Injury
Where do anti-apoptotic proteins reside?
In the outer mitochondrial membranes, cytosol, and ER membranes.
p.3
Overview of Cellular Responses to Stress and Noxious Stimuli
How does pathology relate to clinical care?
It provides the basis for clinical care and therapy.
p.17
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What types of samples are commonly analyzed in histopathology?
Biopsy specimens and surgical resections.
What is necrosis?
Denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell.
How does apoptosis relate to neurodegenerative diseases?
Apoptosis is caused by mutations and misfolded proteins.
p.38
Reversible Cell Injury
What are the consequences of reversible cell injury?
Decreased generation of ATP, loss of cell membrane integrity, defects in protein synthesis, cytoskeletal damage, and DNA damage.
What is the appearance of the area of necrosis in caseous necrosis?
Friable white appearance.
What happens to membrane integrity during necrosis?
There is no membrane integrity; contents often leak out, causing inflammation in the surrounding tissue.
p.4
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What does systemic pathology examine?
The alterations and underlying mechanisms in organ-specific diseases.
p.33
Overview of Cellular Responses to Stress and Noxious Stimuli
What may happen to cell injury over time?
It may progress through a reversible stage and culminate in cell death.
p.37
Reversible Cell Injury
What happens to cells immediately after the onset of injury?
They become rapidly nonfunctional, although they may still be viable.
What is apoptosis?
A pathway of cell death induced by a tightly regulated suicide program.
p.52
Mechanisms of Cell Injury
What is coagulative necrosis?
A type of tissue necrosis where the architecture of dead tissues is preserved for some days.
p.28
Overview of Cellular Responses to Stress and Noxious Stimuli
What is homeostasis?
The process of maintaining a steady state within the cell.
p.16
Overview of Cellular Responses to Stress and Noxious Stimuli
What is a cytology specimen?
A sample of cells used for diagnostic purposes.
What are apoptotic bodies?
Fragments that apoptotic cells break up into.
p.17
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is histopathology?
The study of tissue changes caused by disease.
What causes the deposition in fibrinoid necrosis?
Complexes of antigens and antibodies in the walls of arteries.
What is pyroptosis?
A form of programmed cell death accompanied by the release of fever-inducing cytokine IL-1.
What happens to the nucleus in a necrotic cell over time?
It totally disappears within a day or two.
p.100
Mechanisms of Cell Injury
What aspects of a cell can affect its response to injury?
Nutritional and hormonal status, metabolic needs, and vulnerability.
p.63
Overview of Cellular Responses to Stress and Noxious Stimuli
What does the term 'apoptosis' mean in Greek?
It refers to 'falling off.'
p.36
Mechanisms of Cell Injury
What are the first alterations in cell injury?
Molecular or biochemical level changes.
What is an example of cell loss in proliferating cell populations?
Loss of immature lymphocytes in the bone marrow and thymus.
p.71
Mechanisms of Cell Injury
What causes the initiation of apoptosis in the intrinsic pathway?
Increased permeability of the mitochondrial outer membrane.
Is apoptosis a controlled process?
Yes, it is a highly regulated and programmed process.
p.28
Overview of Cellular Responses to Stress and Noxious Stimuli
What defines a normal cell?
A narrow range of function and structure, including its state of metabolism, differentiation, and specialization.
p.92
Mechanisms of Cell Injury
What initiates the series of events leading to necroptosis?
Cross-linking of TNFR1 by TNF.
What is the significance of eliminating lymphocytes that recognize self antigens?
It helps prevent autoimmune diseases.
p.92
Mechanisms of Cell Injury
What is the outcome of the molecular mechanism of TNF-mediated necroptosis?
Plasma membrane disruption, cell death, and inflammation.
p.28
Adaptations of Cellular Growth and Differentiation
What are adaptations in cellular responses?
Reversible functional and structural responses to changes in physiologic states and some pathologic stimuli.
p.7
Mechanisms of Cell Injury
What are examples of genetic causes of disease?
Inherited mutations and disease-associated gene variants or polymorphisms.
What can defective apoptosis result in?
Failure to eliminate potentially harmful cells, leading to autoimmune disorders.
p.52
Mechanisms of Cell Injury
What causes coagulative necrosis in tissues?
Ischemia caused by obstruction in a vessel.
p.88
Mechanisms of Cell Injury
What is the role of perforin in CTL-mediated apoptosis?
It promotes the entry of granzymes into target cells.
p.17
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What stains are often used in histopathology?
Hematoxylin and eosin (H&E) stains.
p.15
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What are resection specimens?
Tissues or organs removed during surgery for diagnostic or treatment purposes.
p.74
Mechanisms of Cell Injury
What maintains cell viability in the intrinsic pathway of apoptosis?
Induction of anti-apoptotic proteins such as BCL2 by survival signals.
p.55
Mechanisms of Cell Injury
In which conditions is liquefactive necrosis commonly seen?
In focal bacterial or fungal infections.
What is necrosis?
A form of cell injury that results in the premature death of cells in living tissue.
p.24
Adaptations of Cellular Growth and Differentiation
What is cartilage?
A flexible connective tissue found in various parts of the body.
How do CTLs kill target cells?
By directly inducing the effector phase of apoptosis.
p.19
Mechanisms of Cell Injury
What can result from severe or prolonged stress on cells?
Cellular injury or death.
p.42
Reversible Cell Injury
In which types of cells can lipid vacuoles appear during fatty change?
Hepatocytes and myocardial cells.
p.18
Overview of Cellular Responses to Stress and Noxious Stimuli
What is cytopathology?
A branch of pathology that studies and diagnoses diseases at the cellular level.
p.24
Overview of Cellular Responses to Stress and Noxious Stimuli
What type of tissue is epithelium?
A type of tissue that covers body surfaces and lines cavities.
p.72
Mechanisms of Cell Injury
What is the function of anti-apoptotic proteins?
They keep the mitochondrial outer membrane impermeable and prevent leakage of cytochrome c and other death-inducing proteins into the cytosol.
p.45
Reversible Cell Injury
What are the plasma membrane alterations observed in reversible cell injury?
Blebbing, blunting, and loss of microvilli.
What is apoptosis?
A regulated mechanism of cell death.
p.24
Adaptations of Cellular Growth and Differentiation
What is bone classified as?
A type of connective tissue that provides structural support.
p.45
Reversible Cell Injury
What changes occur in mitochondria during reversible cell injury?
Swelling and the appearance of small amorphous densities.
What is the purpose of apoptosis?
To eliminate unwanted and irreparably damaged cells.
p.15
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
Why are resection specimens important?
They provide critical information for diagnosis, treatment planning, and understanding disease progression.
What triggers ferroptosis?
Excessive intracellular levels of iron or reactive oxygen species.
p.45
Reversible Cell Injury
What happens to the endoplasmic reticulum (ER) during reversible cell injury?
Dilation of the ER and detachment of polysomes; intracytoplasmic myelin figures may be present.
What is apoptosis?
A programmed cell death process that occurs in a regulated manner.
What induces apoptosis through DNA damage?
Radiation or chemotherapeutic agents.
p.69
Mechanisms of Cell Injury
What is critical for the regulation of apoptosis?
A balance between pro-apoptotic and anti-apoptotic proteins.
What is cell death?
The end result of progressive cell injury and a crucial event in the evolution of disease in any tissue or organ.
How do macrophages target apoptotic cells?
By producing proteins that bind specifically to apoptotic cells.
What occurs to lysosomal and plasma membranes in irreversible injury?
Rupture of lysosomal and plasma membranes.
p.48
Mechanisms of Cell Injury
What are myelin figures?
Large, whorled phospholipid masses from damaged cell membranes.
p.4
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What does GIS pathology refer to?
Gastrointestinal system pathology.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
What examination involves the visual assessment of tissues without a microscope?
Macroscopic (Gross) examination.
p.98
Autophagy in human diseases
How does mutant huntingtin affect autophagy in Huntington's disease?
Mutant huntingtin impairs autophagy.
p.41
Reversible Cell Injury
What does reversible cell injury imply?
Cellular damage that can be repaired.
p.9
Mechanisms of Cell Injury
What are some limitations of morphology?
Identical lesions may have distinct molecular mechanisms; different courses, therapeutic responses, and prognosis.
p.98
Autophagy in human diseases
What role does autophagy play in infectious diseases?
Many pathogens, like mycobacteria and Shigella spp., are degraded by autophagy.
What initiates the death receptor (extrinsic) pathway?
Engagement of death receptors by ligands on adjacent cells.
What happens to hormone-dependent tissues upon hormone withdrawal?
Involution occurs, leading to cell breakdown, such as endometrial cell breakdown during the menstrual cycle.
p.12
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the purpose of an excisional biopsy?
For histopathological examination using Hematoxylin-Eosin staining.
What is the major mechanism of apoptosis?
The Intrinsic (Mitochondrial) Pathway.
p.100
Mechanisms of Cell Injury
How does the vulnerability of different muscle cells affect their response to injury?
Striated muscle cells in the leg are more resilient compared to striated muscle cells in the heart.
What are the morphological changes associated with necrosis?
Damage to cell membranes, loss of ion homeostasis, and lysosomal enzymes digesting the cell.
What role does apoptosis play in autoimmune disorders?
Defective apoptosis leads to the survival of lymphocytes that can react against self antigens.
Why is it important to eliminate potentially harmful self-reactive lymphocytes?
To prevent reactions against one’s own tissues.
p.72
Mechanisms of Cell Injury
What do pro-apoptotic proteins promote?
Mitochondrial outer membrane permeability.
p.55
Mechanisms of Cell Injury
What causes the accumulation of leukocytes in liquefactive necrosis?
The liberation of enzymes.
p.85
Cellular Responses to Stress and Toxic Insults
What happens to IRE1 when misfolded proteins are detected?
IRE1 forms oligomers and is activated by phosphorylation.
p.43
Reversible Cell Injury
What microscopic feature indicates cellular swelling?
Small clear vacuoles in the cytoplasm, which are distended and pinched-off segments of the ER.
What is a key feature of the nucleus in apoptosis?
The nucleus may break up, producing two or more fragments.
How long may it take for morphologic manifestations of necrosis to appear compared to reversible damage?
Necrosis takes more time than reversible damage.
p.94
Mechanisms of Cell Injury
How does ferroptosis affect membrane function?
It disrupts fluidity, lipid-protein interactions, ion and nutrient transport, and signaling pathways.
p.9
Mechanisms of Cell Injury
How can morphologic changes be observed?
Through gross examination and microscopy.
p.98
Autophagy in human diseases
What role does autophagy play in neurodegenerative disorders?
Dysregulation of autophagy is involved in neurodegenerative disorders.
What are the characteristics of necroptosis that resemble necrosis?
Loss of ATP, swelling of the cell and organelles, generation of ROS, release of lysosomal enzymes, and ultimately rupture of the plasma membrane.
What are apoptotic bodies composed of?
Cytoplasm and tightly packed organelles, with or without nuclear fragments.
What occurs when the level of misfolded proteins is too high?
The mitochondrial pathway of apoptosis is induced, leading to cell death.
p.66
Mechanisms of Cell Injury
What triggers intrinsic mechanisms to induce apoptosis in cases of DNA damage?
When repair mechanisms cannot cope with the injury, such as from radiation, cytotoxic anticancer drugs, and hypoxia.
p.48
Mechanisms of Cell Injury
What can happen to myelin figures in necrotic tissue?
They can be phagocytosed by other cells or degraded into fatty acids.
What leads to apoptotic cell death due to the accumulation of misfolded proteins?
Excessive accumulation in the endoplasmic reticulum (ER) leads to ER stress and apoptotic cell death.
p.4
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What does neuropathology focus on?
Diseases of the nervous system.
What can result from DNA damage in cells lacking functional p53?
Mutations that lead to neoplastic transformation.
p.35
Mechanisms of Cell Injury
What is hypoxia and how does it affect cells?
Hypoxia is oxygen deprivation that reduces aerobic oxidative respiration.
What characterizes cell death?
Irreversible damage leading to the loss of cell function.
p.5
Mechanisms of Cell Injury
What are clinical manifestations?
The functional consequences of the changes caused by the disease.
What is necrosis?
An 'accidental' and unregulated form of cell death characterized by damage to cell membranes and loss of ion homeostasis.
p.18
Overview of Cellular Responses to Stress and Noxious Stimuli
What does cytopathology primarily focus on?
The examination of cells to identify abnormalities and diseases.
p.4
Mechanisms of Cell Injury
What is general pathology focused on?
The common reactions of cells and tissues to injurious stimuli.
What do granzymes activate?
A variety of cellular caspases.
p.43
Reversible Cell Injury
How is cellular swelling typically observed?
It is difficult to appreciate with the light microscope but may be more apparent at the organ level.
What is a characteristic feature of cell shrinkage in apoptosis?
The cell is smaller in size, and the cytoplasm is dense.
p.85
Cellular Responses to Stress and Toxic Insults
What detects misfolded proteins in the endoplasmic reticulum (ER)?
Sensors in the ER membrane, such as the kinase IRE1.
p.43
Reversible Cell Injury
What are the visible signs of cellular swelling at the organ level?
Pallor, increased turgor, and increase in weight of the organ.
p.18
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What types of diseases can cytopathology help diagnose?
Cancer, infections, and inflammatory diseases.
p.24
Adaptations of Cellular Growth and Differentiation
What is the primary function of connective tissue?
To support, bind together, and protect tissues and organs.
What surrounds the area of necrosis in caseous necrosis?
A distinctive inflammatory border.
p.10
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What are functional abnormalities in the context of disease?
The end results of genetic, biochemical, and structural changes in cells and tissues.
p.48
Mechanisms of Cell Injury
What morphological change occurs in necrotic cells due to glycogen loss?
A more glassy homogeneous appearance.
p.15
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
How are resection specimens typically processed for analysis?
They are fixed, sectioned, and stained for microscopic examination.
p.72
Mechanisms of Cell Injury
What are the sensor proteins involved in apoptosis?
BAD, BIM, BID, Puma, and Noxa.
p.55
Mechanisms of Cell Injury
How does hypoxic death of cells in the central nervous system manifest?
As liquefactive necrosis.
p.29
Adaptations of Cellular Growth and Differentiation
What does hyperplasia refer to in cellular responses?
An increase in the number of cells.
What happens to p53 protein when DNA is damaged?
It accumulates in cells and arrests the cell cycle at the G1 phase.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the first step in the daily practice of a pathology laboratory?
Specimen reception and registration.
p.98
Autophagy in human diseases
What is the effect of autophagy in Alzheimer's disease?
Accelerated neurodegeneration occurs due to impaired autophagy.
What are 'eat me' signals in the context of apoptosis?
Numerous receptors on phagocytes and ligands on apoptotic cells that facilitate binding and engulfment.
p.74
Mechanisms of Cell Injury
What is the consequence of BAX and BAK forming channels in the mitochondrial membrane?
Leakage of cytochrome c and other proteins, leading to caspase activation and apoptosis.
What characterizes the process of apoptosis?
It is a highly regulated process driven by a series of genetic pathways.
p.58
Mechanisms of Cell Injury
What does fat necrosis denote in medical terminology?
It does not denote a specific pattern of necrosis.
p.70
Mechanisms of Cell Injury
What are the two pathways that culminate in the activation of caspases?
The mitochondrial pathway and the death receptor pathway.
Is necrosis a controlled process?
No, it is uncontrolled and accidental.
p.85
Overview of Cellular Responses to Stress and Noxious Stimuli
What is IRE1 also known as?
Inositol requiring enzyme-1.
What are the signs of necrosis in epithelial cells?
Loss of nuclei, fragmentation of cells, and leakage of contents.
p.48
Mechanisms of Cell Injury
What are some electron microscopy findings in necrotic cells?
Discontinuities in membranes, dilation of mitochondria, and aggregates of denatured protein.
p.31
Pathologic Calcification
What is pathologic calcification?
Deposition of calcium at sites of cell death.
How do caspases contribute to nuclear fragmentation?
By degrading structural components of the nuclear matrix.
p.55
Mechanisms of Cell Injury
What is liquefactive necrosis?
It is the digestion of dead cells and the transformation of tissue into a liquid viscous mass.
p.69
Mechanisms of Cell Injury
What are proenzymes or zymogens?
Inactive forms of enzymes that undergo cleavage to become active.
p.52
Mechanisms of Cell Injury
In which organs does coagulative necrosis occur due to ischemia?
In all organs except the brain.
p.38
Reversible Cell Injury
What happens if the injurious stimulus abates in reversible cell injury?
The cell can repair the derangements and return to normalcy.
What is observed on microscopic examination of caseous necrosis?
Structureless collection of fragmented or lysed cells and amorphous granular debris.
p.69
Mechanisms of Cell Injury
What are the two phases of apoptosis?
The initiation phase and the execution phase.
What role do soluble factors secreted by apoptotic cells play?
They recruit phagocytes to the site of cell death.
p.94
Mechanisms of Cell Injury
What is a key result of ferroptosis?
Unchecked membrane lipid peroxidation.
p.12
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What staining method is commonly used for histopathological examination?
Hematoxylin-Eosin staining.
How long may the digestion of cellular contents and host response take to develop after necrosis?
It may take hours to develop.
p.71
Mechanisms of Cell Injury
Which family of proteins tightly controls the release of mitochondrial pro-apoptotic proteins?
The BCL2 family of proteins.
What severe damage occurs in irreversible cell injury?
Severe mitochondrial damage with depletion of ATP.
What occurs during the formation of cytoplasmic blebs in apoptosis?
The apoptotic cell shows extensive surface blebbing and fragments into membrane-bound apoptotic bodies.
p.15
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What role do pathologists play in the evaluation of resection specimens?
They analyze the specimens to provide diagnoses and inform treatment decisions.
p.85
Cellular Responses to Stress and Toxic Insults
What does the adaptive unfolded protein response do?
It protects the cell from the harmful consequences of misfolded proteins.
p.43
Reversible Cell Injury
What change occurs in staining during cellular swelling?
Increased eosinophilic staining.
p.41
Cellular Responses to Stress and Toxic Insults
What are the three main outcomes of cellular responses to stress?
Adaptation, injury, and death.
What role does cell death play in embryogenesis?
It is a normal and essential process.
p.10
Mechanisms of Cell Injury
What initiates all forms of disease?
Molecular or structural alterations in cells.
What are the three groups into which the BCL family is divided?
Pro-apoptotic, anti-apoptotic, and those with BCL2 homology (BH) domains.
p.31
Cellular Responses to Stress and Toxic Insults
What is autophagy?
An adaptive cellular response triggered by nutrient deprivation.
What happens to plasma membranes during apoptosis?
Plasma membranes are thought to remain intact until the last stages of apoptosis.
p.83
Reversible Cell Injury
What external factors can lead to protein misfolding?
Deprivation of glucose and oxygen, and stress such as heat.
p.9
Mechanisms of Cell Injury
What additional analyses can contribute to understanding disease?
Molecular analysis and next generation sequencing.
p.98
Autophagy in human diseases
What happens to tuberculosis susceptibility with macrophage-specific deletion of Atg5?
It increases susceptibility to tuberculosis.
What is the difference between reversible cell injury and cell death?
Reversible cell injury can restore normal function, while cell death is irreversible.
What role does p53 serve following genotoxic stress?
It acts as a critical 'life or death' switch.
What triggers necrosis?
Severe injury, lack of blood flow, or toxins.
p.70
Mechanisms of Cell Injury
What is formed in the death receptor pathway to activate caspases?
A death-inducing signaling complex (DISC) from adaptor proteins.
p.93
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What effects does IL-1 have in the body?
Induces leukocyte recruitment and fever.
p.100
Mechanisms of Cell Injury
What role do genetic polymorphisms play in cellular responses to injury?
They influence the responses of different individuals to various injurious agents.
What triggers necrosis?
Ischemia, exposure to toxins, various infections, and trauma.
What is a key characteristic of apoptosis in terms of host reaction?
It results in the least possible host reaction.
p.4
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What area of pathology studies diseases of the cardiovascular system?
Cardiovascular system pathology.
p.72
Mechanisms of Cell Injury
What is the role of pro-apoptotic proteins in apoptosis?
They form a channel in the outer mitochondrial membrane, allowing leakage of cytochrome c.
p.29
Adaptations of Cellular Growth and Differentiation
What is hypertrophy in cellular responses?
An increase in the size of cells and functional activity.
What is thrombospondin?
An adhesive glycoprotein that coats some apoptotic bodies, recognized by phagocytes.
What is a characteristic feature of caseous necrosis?
Formation of a granuloma.
How does apoptosis differ from necrosis?
Apoptosis involves rapid removal of cellular debris without leakage of cellular contents and no inflammatory reaction.
How does apoptosis affect surrounding tissue?
It usually does not cause inflammation and is a clean process.
p.4
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What does hematopathology study?
Diseases related to blood and bone marrow.
What are some causes of cell death?
Ischemia (reduced blood flow), infection, and toxins.
What is the role of apoptosis in pathologic conditions?
It eliminates cells that are injured beyond repair without eliciting a host reaction, limiting collateral tissue damage.
p.10
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the significance of clinicopathologic correlations?
They are very important in the study of disease.
What happens when cell injury becomes irreversible?
The cell cannot recover and dies.
How are apoptotic cells removed from the body?
They are rapidly ingested by phagocytes and degraded by lysosomal enzymes.
p.83
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
Which neurodegenerative diseases are associated with protein misfolding?
Alzheimer's, Huntington's, Parkinson's diseases, and type 2 diabetes.
p.94
Mechanisms of Cell Injury
What ultrastructural changes occur during ferroptosis?
Loss of mitochondrial cristae and ruptured outer mitochondrial membrane.
p.8
Mechanisms of Cell Injury
What is pathogenesis?
The sequence of cellular, biochemical, and molecular events from the initial cause to the manifestation of the disease.
p.29
Overview of Cellular Responses to Stress and Noxious Stimuli
What can happen to a cell after an adaptive response?
The cell can recover to its original state without any harmful consequences.
p.94
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
In which conditions is ferroptosis associated?
Cancer, neurodegenerative diseases, and stroke.
p.25
Reversible Cell Injury
What is reversible cell injury?
A type of cell injury that can be repaired if the stressor is removed.
p.9
Mechanisms of Cell Injury
How has the field of diagnostic pathology expanded?
It now includes molecular biologic and proteomic approaches for analyzing disease states.
p.62
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the focus of the introduction to pathology?
It provides foundational knowledge about disease processes.
p.30
Mechanisms of Cell Injury
What are the possible outcomes of cellular injury?
Reversible injury, irreversible injury, and cell death.
Which kinases are involved in necroptosis?
Receptor associated kinase 1 and 3 (RIP1 and RIP3).
What triggers apoptosis?
Cellular signals, such as DNA damage or developmental cues.
p.70
Mechanisms of Cell Injury
What is the end result of both the mitochondrial and death receptor pathways?
Activation of caspases leading to apoptosis.
p.46
Intracellular Accumulations
What are intracellular accumulations?
The buildup of substances within cells that can lead to dysfunction.
p.99
Mechanisms of Cell Injury
What does the unfolded protein response indicate?
Endoplasmic reticulum stress.
What initiates the Extrinsic (Death Receptor-Initiated) Pathway of Apoptosis?
Engagement of plasma membrane death receptors on various cells.
p.74
Mechanisms of Cell Injury
What triggers the intrinsic pathway of apoptosis?
Loss of survival signals, DNA damage, and other insults.
What is apoptosis?
A form of cell death characterized by nuclear dissolution and fragmentation of the cell without complete loss of membrane integrity.
What are the characteristic features of pyroptosis?
Swelling of cells, loss of plasma membrane integrity, and release of inflammatory mediators.
p.85
Cellular Responses to Stress and Toxic Insults
What is triggered by the detection of misfolded proteins in the ER?
An adaptive unfolded protein response.
What is necroptosis?
A form of cell death that shares aspects of both necrosis and apoptosis.
p.69
Mechanisms of Cell Injury
What are the two distinct pathways that converge on caspase activation?
The mitochondrial pathway and the death receptor pathway.
When can light microscopic changes of cell death be observed after ischemia?
4 to 12 hours after the onset of ischemia.
p.9
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What may morphologic changes indicate?
They may be characteristic of a disease or diagnostic of an etiologic process.
p.46
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the focus of the introduction to pathology?
An overview of the fundamental concepts in pathology.
p.83
Mechanisms of Cell Injury
What causes the intracellular accumulation of abnormally folded proteins?
Genetic mutations, aging, or unknown environmental factors.
p.44
Reversible Cell Injury
What do normal kidney tubules with viable epithelial cells look like?
They appear healthy and intact.
What are the morphological features of apoptosis?
Cell shrinkage, chromatin condensation, and formation of apoptotic bodies.
What is the terminal unfolded protein response?
It refers to the situation where irreparably damaged cells die due to excessive misfolded proteins.
p.44
Reversible Cell Injury
What are the characteristics of early (reversible) ischemic injury?
Surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells.
p.48
Mechanisms of Cell Injury
What results from the calcification of fatty acid residues in necrosis?
The generation of calcium soaps.
p.70
Mechanisms of Cell Injury
What role do BCL2 family proteins play in apoptosis?
They regulate mitochondrial permeability and influence the balance between pro-apoptotic and anti-apoptotic proteins.
p.8
Mechanisms of Cell Injury
What is essential to understand cystic fibrosis?
The defective gene, the gene product, the biochemical events, and the morphologic events.
p.58
Mechanisms of Cell Injury
What happens to fat cell membranes in the peritoneum during fat necrosis?
They are liquefied by pancreatic enzymes.
How can cell death occur in viral infections?
It may be induced by the virus itself or by the host immune response, such as in adenovirus, HIV infections, or viral hepatitis.
p.98
Autophagy in human diseases
What is the relationship between autophagy and inflammatory bowel diseases?
Autophagy is implicated in the pathology of inflammatory bowel diseases.
p.56
Mechanisms of Cell Injury
What is gangrenous necrosis commonly applied to?
A limb, generally the lower leg, that has lost its blood supply.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the purpose of staining in microscopy?
To enhance the visibility of tissue structures.
What are some other mechanisms of cell death besides necrosis and apoptosis?
Necroptosis, Pyroptosis, and Ferroptosis.
p.56
Mechanisms of Cell Injury
What happens to tissue in gangrenous necrosis?
It undergoes necrosis involving multiple tissue planes.
p.35
Mechanisms of Cell Injury
How do immunologic reactions contribute to cell injury?
Through injurious reactions to endogenous self antigens, such as in autoimmune diseases.
p.26
Intracellular Accumulations
What are intracellular accumulations?
The buildup of substances within cells that can lead to dysfunction.
p.47
Mechanisms of Cell Injury
What enzymes contribute to the digestion of cellular contents during necrosis?
Enzymes from the lysosomes of dying cells and from leukocytes.
What is released from the mitochondrial intermembrane space during apoptosis?
Death-inducing molecules such as cytochrome c.
p.100
Mechanisms of Cell Injury
Which cellular components are most frequently affected by injurious stimuli?
Mitochondria, cell membranes, protein synthesis machinery, and DNA.
p.9
Mechanisms of Cell Injury
What are morphologic changes?
Structural alterations in cells or tissues.
p.98
Autophagy in human diseases
How is autophagy related to cancer?
Dysregulation of autophagy can contribute to cancer development.
What occurs to lymphocytes at the end of an immune response?
They die due to deprivation of survival signals, such as growth factors.
p.12
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the purpose of resections in tissue sampling?
For histopathological examination.
p.10
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What do functional abnormalities lead to?
Clinical manifestations (symptoms and signs) of disease.
What occurs if the unfolded protein response cannot manage the accumulation of misfolded proteins?
The cell activates caspases and induces apoptosis, a process known as ER stress.
What is a characteristic of cell death in ferroptosis?
Loss of plasma membrane permeability, resembling necrosis.
p.29
Adaptations of Cellular Growth and Differentiation
What is atrophy in the context of cellular responses?
A decrease in the size and metabolic activity of cells.
What are the two major pathways that initiate apoptosis?
Mitochondrial (intrinsic) pathway and Death receptor (extrinsic) pathway.
What triggers necroptosis?
Genetically programmed signal transduction events that culminate in cell death.
What characterizes the mitochondrial (intrinsic) pathway of apoptosis?
Leakage of pro-apoptotic proteins from the mitochondrial membrane into the cytoplasm.
What happens to cells with mutated or absent TP53?
They fail to undergo p53-mediated apoptosis and may survive with damaged DNA.
What are some other mechanisms of cell death besides necrosis and apoptosis?
Necroptosis, Pyroptosis, and Ferroptosis.
What is cell death?
The irreversible loss of cellular function and structure.
In which diseases is the accumulation of misfolded proteins particularly relevant?
In degenerative diseases of the central nervous system and other organs.
p.10
Mechanisms of Cell Injury
What do functional abnormalities influence in a disease?
The clinical course and outcome.
p.41
Mechanisms of Cell Injury
What are mechanisms of cell injury?
Processes that lead to cellular damage and dysfunction.
What initiates necroptosis?
Ligation of the receptor TNFR1 by its ligand.
p.35
Mechanisms of Cell Injury
What are some causes of ischemia?
Reduced blood flow, inadequate oxygenation due to cardiorespiratory failure, decreased oxygen-carrying capacity (anemia, carbon monoxide poisoning), and severe blood loss.
What accompanies aging in cells?
Characteristic morphologic and functional changes.
p.35
Mechanisms of Cell Injury
What are physical agents that can cause cell injury?
Mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, radiation, and electric shock.
p.30
Reversible Cell Injury
What characterizes reversible cell injury?
Cellular function can return to normal after the removal of the stressor.
p.41
Pathologic Calcification
What is pathologic calcification?
Abnormal deposition of calcium salts in tissues.
p.25
Intracellular Accumulations
What are intracellular accumulations?
Build-up of substances within cells due to metabolic disturbances.
p.30
Adaptations of Cellular Growth and Differentiation
How do cells adapt to stress?
Through mechanisms such as hypertrophy, hyperplasia, atrophy, and metaplasia.
What is cellular aging?
The gradual decline in cellular function and viability over time.
What are BH3-only proteins responsible for?
They sense damage and are activated in response to stress.
What happens to chromatin during apoptosis?
Chromatin condenses and aggregates peripherally under the nuclear membrane into dense masses.
p.15
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What types of conditions might require the examination of resection specimens?
Cancer, inflammatory diseases, and other pathological conditions.
p.33
Reversible Cell Injury
What defines reversible cell injury?
Early stages or mild forms of injury, including reduced oxidative phosphorylation and cellular swelling.
p.45
Reversible Cell Injury
What nuclear alterations are associated with reversible cell injury?
Disaggregation of granular and fibrillar elements.
p.18
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the significance of cytopathology in medical diagnostics?
It allows for early detection and treatment of diseases at the cellular level.
p.83
Cellular Responses to Stress and Toxic Insults
What happens to unfolded or misfolded proteins in the endoplasmic reticulum (ER)?
They accumulate and trigger the unfolded protein response.
p.74
Mechanisms of Cell Injury
What do sensors activated by loss of survival signals do?
They antagonize the anti-apoptotic proteins.
p.43
Reversible Cell Injury
What is another name for the pattern of nonlethal injury characterized by cellular swelling?
Hydropic change or vacuolar degeneration.
p.48
Mechanisms of Cell Injury
What happens to the cytoplasm when enzymes digest cytoplasmic organelles in necrosis?
The cytoplasm becomes vacuolated.
p.41
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the focus of the study of pathology?
The study of disease and its effects on the body.
p.72
Mechanisms of Cell Injury
What is the function of sensor proteins in apoptosis?
They act as sensors of cellular stress and damage, regulating the balance between anti-apoptotic and pro-apoptotic proteins.
p.12
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is exfoliative cytology?
A method of obtaining cell samples via smear for cytopathology.
p.47
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
How quickly can cardiac-specific enzymes and proteins be detected in the blood after myocardial cell necrosis?
As early as 2 hours after necrosis.
What are the morphological features of necrosis?
Cell swelling, rupture, and inflammation.
p.9
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the role of morphology in diagnostic pathology?
To determine the nature of disease.
p.29
Adaptations of Cellular Growth and Differentiation
What does metaplasia mean in cellular responses?
A change in the phenotype of cells.
p.26
Causes of Cell Injury
What are the primary causes of cell injury?
Oxygen deprivation, physical agents, chemical agents and drugs, infectious agents, immunologic reactions, genetic abnormalities, and nutritional imbalances.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the purpose of sampling in a pathology lab?
To collect tissue for further analysis.
p.10
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
How do clinical manifestations appear in relation to disease?
They appear as a result of functional abnormalities.
p.26
Reversible Cell Injury
What is reversible cell injury?
A type of cell injury that can recover and restore normal function.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
Which substances are involved in tissue processing?
Formaldehyde, water, alcohol, xylene, paraffin.
What is the function of Fas ligand (FasL) in T cells?
To eliminate self-reactive lymphocytes.
p.8
Mechanisms of Cell Injury
What are the morphologic events associated with cystic fibrosis?
The formation of cysts and fibrosis in the lungs, pancreas, and other organs.
p.58
Mechanisms of Cell Injury
What do released lipases do to triglyceride esters in fat cells?
They split the triglyceride esters.
p.44
Mechanisms of Cell Injury
What is a key difference between reversible injury and necrosis?
Reversible injury can be repaired, while necrosis is irreversible.
p.58
Mechanisms of Cell Injury
What is produced when fatty acids combine with calcium in fat necrosis?
Grossly visible chalky-white areas, known as fat saponification.
In what conditions can necroptosis occur?
In both physiologic and pathologic conditions, such as during mammalian bone growth plate formation and in diseases like steatohepatitis and Parkinson's disease.
p.58
Mechanisms of Cell Injury
What is observed on histologic examination of necrotic fat cells?
Foci of shadowy outlines of necrotic fat cells with basophilic calcium deposits and surrounding inflammatory reaction.
p.46
Pathologic Calcification
What is pathologic calcification?
The abnormal deposition of calcium salts in tissues.
p.48
Mechanisms of Cell Injury
What is increased eosinophilia in necrosis associated with?
The loss of cytoplasmic RNA and denatured cytoplasmic proteins.
What characterizes irreversible injury and cell death?
Persistent or excessive injury, leading to a 'point of no return.'
p.31
Mechanisms of Cell Injury
What are the stages of cell injury?
Adaptation, reversible injury, irreversible injury, and cell death.
How does necrosis typically affect surrounding tissue?
It often causes inflammation and damage to surrounding tissues.
p.33
Reversible Cell Injury
What causes cellular swelling in reversible cell injury?
Changes in ion concentrations and water influx.
What is a key feature of the death receptors?
They contain a cytoplasmic domain involved in protein-protein interactions called the death domain.
p.71
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What happens when BCL2 is overexpressed?
It can lead to certain B cell lymphomas due to chromosomal translocations.
p.24
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the function of muscle tissue?
To facilitate movement of the body and its parts.
p.33
Reversible Cell Injury
What alterations occur in reversible cell injury?
Alterations in intracellular organelles like mitochondria and the cytoskeleton.
What is necroptosis?
A regulated form of necrosis that is also considered a type of programmed cell death.
Which are the best-known death receptors?
Type 1 TNF receptor (TNFR1) and Fas (CD95).
p.36
Reversible Cell Injury
What may happen to cell swelling within an hour or two?
It may progress to irreversibility.
What proteins can coat apoptotic bodies to aid in their recognition?
Natural antibodies and complement system proteins, notably C1q.
p.25
Overview of Cellular Responses to Stress and Noxious Stimuli
What are the three main outcomes of cellular responses to stress?
Adaptation, injury, and death.
p.58
Mechanisms of Cell Injury
What causes focal areas of fat destruction in fat necrosis?
Release of activated pancreatic lipases during acute pancreatitis.
p.31
Intracellular Accumulations
What are intracellular accumulations?
Metabolic derangements in cells leading to accumulations of proteins, lipids, and carbohydrates.
What is autophagy?
A process where cells degrade and recycle components.
p.83
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the collective response triggered by misfolded proteins in the ER?
The unfolded protein response.
p.11
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the function of a microtome in pathology?
To cut thin sections of tissue for examination.
What type of cells do some cytotoxic T lymphocytes kill?
Virus-infected and tumor cells.
p.8
Mechanisms of Cell Injury
What is the aim of linking specific molecular abnormalities to disease manifestations?
To develop new therapeutic approaches.
What does p53 trigger in the apoptosis pathway?
The distal death effector machinery, including caspases.
p.99
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the focus of the introduction to pathology?
Overview of cellular responses to stress and noxious stimuli.
What is a consequence of apoptosis in tumors?
It can occur in tumors and during cellular rejection of transplants.
What is cellular aging?
The gradual decline in cellular function and viability over time.
p.30
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the role of inflammation in cellular responses to injury?
To eliminate the initial cause of cell injury and initiate healing.
p.62
Cellular Responses to Stress and Toxic Insults
What is the relationship between stress and cellular responses?
Cells adapt, become injured, or die in response to stress and toxic insults.
p.30
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the primary focus of cellular responses to injury?
To understand how cells react to harmful stimuli and stress.
p.44
Reversible Cell Injury
What happens to the cytoplasm during early reversible ischemic injury?
It shows increased eosinophilia.
p.26
Immunologic Reactions
How do immunologic reactions contribute to cell injury?
They can cause inflammation and damage to tissues.
p.26
Nutritional Imbalances
What role does nutritional imbalance play in cell injury?
It can lead to deficiencies or excesses that disrupt normal cellular functions.
p.35
Mechanisms of Cell Injury
What types of infectious agents can cause cell injury?
Viruses, rickettsiae, bacteria, fungi, and parasites.
p.99
Mechanisms of Cell Injury
What are general mechanisms of cell injury?
Includes mitochondrial damage, membrane damage, damage to DNA, oxidative stress, disturbance in calcium homeostasis, and endoplasmic reticulum stress.
p.99
Mechanisms of Cell Injury
What is oxidative stress?
Accumulation of oxygen-derived free radicals.
What is cellular aging?
The process of gradual deterioration of cellular function over time.
What happens when cells are deprived of survival signals?
Damaged DNA and misfolded proteins induce ER stress.
p.95
Cellular Responses to Stress and Toxic Insults
How does a starved cell survive?
By cannibalizing itself and recycling the digested contents.
What is formed when cytochrome c binds to APAF-1?
A multimeric structure called the apoptosome.
p.70
Mechanisms of Cell Injury
What happens when there is an imbalance in BCL2 family proteins?
It leads to the leakage of substances from mitochondria that activate caspases.
p.46
Mechanisms of Cell Injury
What are the primary mechanisms of cell injury?
Various factors that lead to cellular damage and dysfunction.
p.41
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What do clinicopathologic correlations involve?
Relationships between clinical findings and pathological changes.
p.46
Adaptations of Cellular Growth and Differentiation
What does cellular adaptation refer to?
The process by which cells adjust to changes in their environment.
p.41
Adaptations of Cellular Growth and Differentiation
What are adaptations of cellular growth and differentiation?
Changes in cell size, number, or type in response to stimuli.
p.8
Mechanisms of Cell Injury
What initiates the pathogenesis process?
The exposure of cells or tissues to an injurious agent.
p.41
Intracellular Accumulations
What are intracellular accumulations?
Build-up of substances within cells due to various factors.
p.99
Reversible Cell Injury
What are the main types of cell injury discussed?
Reversible cell injury and cell death.
What is cellular aging?
The gradual decline in cellular function and viability over time.
p.25
Pathologic Calcification
What is pathologic calcification?
Abnormal deposition of calcium salts in tissues.
p.35
Mechanisms of Cell Injury
What nutritional imbalances can cause cell injury?
Protein-calorie deficiencies, specific vitamin deficiencies, self-imposed deficiencies (anorexia nervosa), and nutritional excesses (cholesterol leading to atherosclerosis, obesity with diabetes and cancer).
p.95
Cellular Responses to Stress and Toxic Insults
What are the three types of autophagy?
Chaperone-mediated autophagy, microautophagy, and macroautophagy.
p.26
Mechanisms of Cell Injury
What mechanisms can lead to cell injury?
Oxygen deprivation, toxic substances, and genetic factors.
What role do cytotoxic T lymphocytes play in viral infections?
They induce apoptosis specific for viral proteins.
p.25
Mechanisms of Cell Injury
What are some mechanisms of cell injury?
Hypoxia, chemical exposure, and infectious agents.
p.25
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What can clinicopathologic correlations help identify?
Specific examples of cell injury and death in clinical settings.
What leads to irreversible cell injury?
Severe damage that results in cell death.
p.56
Mechanisms of Cell Injury
What can superimpose on gangrenous necrosis?
Bacterial infection, leading to more liquefactive necrosis.
p.35
Mechanisms of Cell Injury
What are genetic derangements that can lead to cell injury?
An extra chromosome, single base pair substitutions, deficiency of functional proteins, and accumulation of damaged DNA or misfolded proteins.
p.25
Cellular Responses to Stress and Toxic Insults
What is the focus of cellular responses to stress and toxic insults?
Understanding how cells adapt, become injured, or die under stress.
p.99
Intracellular Accumulations
What are intracellular accumulations?
Build-up of substances within cells due to various stresses.
What does the apoptosome activate?
Caspase-9 (the initiator caspase).
What is the appearance of necrotic cells in coagulative necrosis?
They show preserved cellular outlines with loss of nuclei.
p.66
Adaptations of Cellular Growth and Differentiation
In what context does pathologic atrophy occur?
After duct obstruction in parenchymal organs such as the pancreas, parotid gland, and kidney.
p.35
Mechanisms of Cell Injury
What types of chemical agents can lead to cell injury?
Simple chemicals (glucose, salt, oxygen), poisons (arsenic, cyanide, mercuric salts), environmental pollutants, insecticides, herbicides, recreational drugs, and therapeutic drugs.
What is autophagy?
A process by which cells degrade and recycle components.
p.62
Intracellular Accumulations
What are intracellular accumulations?
Build-up of substances within cells that can lead to injury.
p.30
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is the significance of understanding cellular responses to injury?
It helps in diagnosing and treating various diseases.
p.99
Adaptations of Cellular Growth and Differentiation
What does adaptation in cellular growth and differentiation refer to?
The ability of cells to adjust to stressors.
What does cytochrome c bind to in the apoptosis process?
APAF-1 (apoptosis-activating factor-1).
What does caspase-9 trigger in the apoptosis process?
A cascade of caspase activation by cleaving other pro-caspases.
p.25
Adaptations of Cellular Growth and Differentiation
What are adaptations of cellular growth?
Changes in cell size, number, or type in response to stress.
p.26
Pathologic Calcification
What is pathologic calcification?
The abnormal deposition of calcium salts in tissues.
What is cellular aging?
The gradual decline in cellular function and viability over time.
p.62
Pathologic Calcification
What is pathologic calcification?
Abnormal deposition of calcium salts in tissues.
p.95
Cellular Responses to Stress and Toxic Insults
What is autophagy?
A process in which a cell eats its own contents.
p.95
Cellular Responses to Stress and Toxic Insults
What characterizes microautophagy?
Inward invagination of lysosomal membrane for delivery.
What is released into the cytoplasm as a result of BAX and BAK activation?
Proteins from the inner mitochondrial membrane, including cytochrome c.
p.99
Cellular Responses to Stress and Toxic Insults
What are cellular responses to stress and toxic insults?
Adaptation, injury, and death.
p.14
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is an incisional biopsy?
A surgical procedure where a portion of a lesion is removed for diagnostic purposes.
p.62
Adaptations of Cellular Growth and Differentiation
What is meant by cellular adaptations?
Changes in cell structure or function in response to stress.
p.56
Mechanisms of Cell Injury
What is wet gangrene?
Gangrenous necrosis with superimposed bacterial infection causing liquefactive necrosis.
p.99
Mechanisms of Cell Injury
What is the significance of calcium homeostasis in cellular injury?
Disturbance in calcium homeostasis can lead to cell injury.
What stimulates the production of anti-apoptotic proteins like BCL2?
Growth factors and other survival signals.
p.99
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What are some examples of clinicopathologic correlations?
Selected examples of cell injury and death.
p.99
Pathologic Calcification
What is pathologic calcification?
Abnormal deposition of calcium salts in tissues.
What does a wedge-shaped kidney infarct indicate?
It indicates coagulative necrosis in the kidney.
p.95
Cellular Responses to Stress and Toxic Insults
What is chaperone-mediated autophagy?
Direct translocation across the lysosomal membrane by chaperone proteins.
What does cellular aging involve?
The gradual deterioration of cellular function over time.
p.95
Cellular Responses to Stress and Toxic Insults
What are the steps involved in autophagy?
Formation of an isolation membrane from the ER, elongation of the vesicle, maturation of the autophagosome, and fusion with lysosomes.
p.14
Clinicopathologic Correlations: Selected Examples of Cell Injury and Death
What is a punch biopsy?
A technique that uses a circular blade to remove a small core of tissue for examination.
What is observed microscopically at the edge of a kidney infarct?
Normal kidney cells and necrotic cells showing preserved outlines but loss of nuclei.
What phase of apoptosis is mediated by the caspase cascade?
The execution phase of apoptosis.
p.1
Overview of Cellular Responses to Stress and Noxious Stimuli
What is the focus of Medical Pathology?
The study of diseases and their effects on the body.
