What is the focus of Medical Pathology?
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The study of diseases and their effects on the body.
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What is the focus of Medical Pathology?
The study of diseases and their effects on the body.
What happens to necrotic cells and their contents in a living patient?
They disappear due to enzymatic digestion and phagocytosis by leukocytes.
What happens to cells immediately after the onset of injury?
They become rapidly nonfunctional, although they may still be viable.
Who is the professor for the Introduction to Medical Pathology course?
Prof. Dr. Aptullah HAHOLU.
What activates caspase-8 in the extrinsic pathway of apoptosis?
FasL binding to Fas.
What occurs if necrotic cells and debris are not promptly destroyed?
They provide a nidus for the deposition of calcium salts and other minerals.
What can potentially occur if the duration of injury is prolonged?
Irreversible injury and cell death.
What is a key feature of reversible cell injury observed under the light microscope?
Cellular swelling.
What initiates the cascade of caspase activation in apoptosis?
The two initiating pathways converge.
What is apoptosis?
A pathway of cell death induced by a tightly regulated suicide program.
What are the three patterns of nuclear changes due to nonspecific breakdown of DNA?
Karyolysis, Pyknosis, and Karyorrhexis.
What defines a normal cell?
A narrow range of function and structure, including its state of metabolism, differentiation, and specialization.
What is the role of FasL on T cells?
It binds to Fas on the same or neighboring lymphocytes to induce apoptosis.
What do the subsequent events after caspase-8 activation lead to?
Activation of multiple executioner caspases.
What is the term for the calcification that occurs in necrotic tissue?
Dystrophic calcification.
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 triggers apoptosis in hormone-sensitive cells deprived of hormones?
The intrinsic (mitochondrial) pathway.
What characterizes the early stage of cell injury?
Cells may exhibit potentially reversible damage.
What is coagulative necrosis?
A type of tissue necrosis where the architecture of dead tissues is preserved for some days.
What is apoptosis?
A physiological event that removes unwanted, aged, or potentially harmful cells.
What initiates the series of events leading to necroptosis?
Cross-linking of TNFR1 by TNF.
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.
Which caspase is activated by the mitochondrial pathway?
Caspase-9.
What is the definition of pathology?
The study of disease, focusing on structural, biochemical, and functional changes in cells, tissues, and organs.
What occurs during Karyolysis?
The basophilia of the chromatin fades and there is a loss of DNA due to enzymatic degradation by endonucleases.
What do intrinsic enzymes do during apoptosis?
They degrade the cell's own nuclear DNA and nuclear and cytoplasmic proteins.
What is homeostasis?
The process of maintaining a steady state within the cell.
What are the three main cellular responses to stress and toxic insults?
Adaptation, injury, and death.
What is the significance of eliminating lymphocytes that recognize self antigens?
It helps prevent autoimmune diseases.
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.
What are the features of cell shrinkage during apoptosis?
Formation of apoptotic bodies.
What happens to lymphocytes that are not stimulated by antigens and cytokines?
Apoptosis is triggered.
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.
What texture do affected tissues exhibit in coagulative necrosis?
A firm texture due to denaturation of structural proteins and enzymes.
What is a cytology specimen?
A sample of cells used for diagnostic purposes.
When does apoptosis occur?
During development and throughout adulthood.
What is the outcome of the molecular mechanism of TNF-mediated necroptosis?
Plasma membrane disruption, cell death, and inflammation.
What is the first aspect of a disease process?
Etiology; the cause of the disease.
What is another feature of reversible cell injury?
Fatty change.
What are the two main categories of etiology for diseases?
Genetic and acquired.
Which caspases are activated by the death receptor pathway?
Caspases-8 and -10.
What is a common trigger for apoptosis related to cellular environment?
Growth factor deprivation.
What does pathology aim to explain?
The signs and symptoms of diseases.
What are apoptotic bodies?
Fragments that apoptotic cells break up into.
What is characterized by nuclear shrinkage and increased basophilia?
Pyknosis.
What are adaptations in cellular responses?
Reversible functional and structural responses to changes in physiologic states and some pathologic stimuli.
What can result from mutations affecting Fas or FasL?
Autoimmune diseases in humans and mice.
What does cellular adaptation refer to?
The process by which cells adjust to changes in their environment to maintain function.
What process occurs to the fragments of apoptotic cells?
Phagocytosis of fragments.
What is the effect of deprivation of nerve growth factor on neurons?
It triggers apoptosis.
What is fibrinoid necrosis?
A special form of necrosis occurring in immune reactions involving blood vessels.
What is histopathology?
The study of tissue changes caused by disease.
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.
How long may eosinophilic, anucleate cells persist in coagulative necrosis?
For days or weeks.
What is a pathological cause of apoptosis?
Elimination of damaged cells beyond repair.
What is fine needle aspiration?
A minimally invasive procedure to obtain a sample of tissue or fluid.
What factors influence the cellular response to injurious stimuli?
The nature of the injury, its duration, and its severity.
What role does TNF play in necroptosis?
It cross-links TNFR1, triggering downstream events.
What does pathogenesis refer to in a disease process?
The biochemical and molecular mechanisms of disease development.
What do cytotoxic T lymphocytes (CTLs) recognize?
Foreign antigens on the surface of infected host cells.
What is apoptosis?
A normal phenomenon to eliminate no longer needed cells and maintain a steady number of various cell populations.
What can cause fatty change in cells?
Hypoxic injury, various forms of toxic or metabolic injury.
What are the anti-apoptotic proteins mentioned?
BCL2, BCL-XL, and MCL1.
What are executioner caspases responsible for?
They act on many cellular components, including cleaving an inhibitor of a cytoplasmic DNase.
What are examples of genetic causes of disease?
Inherited mutations and disease-associated gene variants or polymorphisms.
What type of cellular damage can lead to apoptosis?
DNA damage.
What techniques are used in pathology?
Molecular, microbiologic, immunologic, and morphologic techniques.
What happens during Karyorrhexis?
The pyknotic nucleus undergoes fragmentation.
What happens to the plasma membrane of apoptotic cells?
It remains intact but its structure is altered, making it a target for phagocytes.
What do adaptations allow a cell to do?
Survive and continue to function by establishing new but altered steady states.
What can result from severe or prolonged stress on cells?
Cellular injury or death.
How does apoptosis affect inflammation?
It does not elicit inflammation, making it more difficult to detect histologically.
Which proteins are decreased in synthesis during the intrinsic pathway of apoptosis?
BCL2 and BCL-XL.
What causes the deposition in fibrinoid necrosis?
Complexes of antigens and antibodies in the walls of arteries.
How does histopathology contribute to understanding diseases?
By examining tissue samples under a microscope to identify abnormalities.
What does fat necrosis involve?
Areas of white chalky deposits representing foci of fat necrosis.
What can defective apoptosis result in?
Failure to eliminate potentially harmful cells, leading to autoimmune disorders.
What role does apoptosis play in the body?
It serves to remove unwanted and potentially harmful cells.
What is a PAP smear?
A test used to screen for cervical cancer by examining cells from the cervix.
How are necrotic cells ultimately removed in coagulative necrosis?
By phagocytosis and digestion by lysosomal enzymes.
What is pyroptosis?
A form of programmed cell death accompanied by the release of fever-inducing cytokine IL-1.
What determines the consequences of cell injury?
The type, state, and adaptability of the injured cell.
What are morphologic changes in the context of disease?
The structural alterations in the cells and organs.
What do CTLs secrete upon activation?
Perforin.
What are some physiological situations where apoptosis occurs during embryogenesis?
Destruction of cells during implantation, organogenesis, developmental involution, and metamorphosis.
In which types of cells can lipid vacuoles appear during fatty change?
Hepatocytes and myocardial cells.
Where do anti-apoptotic proteins reside?
In the outer mitochondrial membranes, cytosol, and ER membranes.
What is caseous necrosis most commonly associated with?
Foci of tuberculous infection.
What are examples of acquired causes of disease?
Infectious, nutritional, chemical, and physical factors.
What is the effect of the DNase being activated by executioner caspases?
It induces cleavage of DNA.
What is a consequence of protein misfolding in cells?
Induction of apoptosis.
How does pathology relate to clinical care?
It provides the basis for clinical care and therapy.
What happens to the nucleus in a necrotic cell over time?
It totally disappears within a day or two.
What are the ultrastructural changes of reversible cell injury?
Plasma membrane alterations, mitochondrial changes, dilation of the ER, and nuclear alterations.
How are dead cells and their fragments handled during apoptosis?
They are rapidly devoured by phagocytes before leaking contents, preventing inflammation.
What is the ultimate consequence of cellular stress if adaptation fails?
Cell death.
What is activated in response to growth factor deprivation that promotes apoptosis?
BIM and other pro-apoptotic members of the BCL2 family.
What types of samples are commonly analyzed in histopathology?
Biopsy specimens and surgical resections.
What is the appearance of fibrinoid necrosis in H&E stains?
A bright pink and amorphous appearance.
What is cytopathology?
A branch of pathology that studies and diagnoses diseases at the cellular level.
What is formed at sites of lipid breakdown during fat necrosis?
Calcium soap (saponification).
What are some conditions associated with increased apoptosis?
Neurodegenerative diseases, ischemic injury (myocardial infarction and stroke), and death of virus-infected cells.
What causes coagulative necrosis in tissues?
Ischemia caused by obstruction in a vessel.
What activates the inflammasome in pyroptosis?
Microbial products.
What type of tissue is epithelium?
A type of tissue that covers body surfaces and lines cavities.
What aspects of a cell can affect its response to injury?
Nutritional and hormonal status, metabolic needs, and vulnerability.
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 happens to hormone-dependent tissues upon hormone withdrawal?
Involution occurs, leading to cell breakdown, such as endometrial cell breakdown during the menstrual cycle.
What are clinical manifestations?
The functional consequences of the changes caused by the disease.
What is the role of perforin in CTL-mediated apoptosis?
It promotes the entry of granzymes into target cells.
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.
What does multifactorial etiology imply?
It arises from the effects of various external triggers on a genetically susceptible individual.
What does the term 'caseous' refer to in caseous necrosis?
Cheese-like appearance.
Which immune cells are involved in mediating apoptosis?
Cytotoxic T lymphocytes.
How do caspases contribute to nuclear fragmentation?
By degrading structural components of the nuclear matrix.
What is the purpose of an excisional biopsy?
For histopathological examination using Hematoxylin-Eosin staining.
What is necrosis?
An 'accidental' and unregulated form of cell death characterized by damage to cell membranes and loss of ion homeostasis.
What is the first manifestation of almost all forms of injury to cells?
Cellular swelling.
What role does pathology play between basic sciences and clinical medicine?
Pathology acts as a bridge between the basic sciences and clinical medicine.
What are the plasma membrane alterations observed in reversible cell injury?
Blebbing, blunting, and loss of microvilli.
What are caspases?
Cysteine proteases that cleave proteins after aspartic residues.
What is necrosis?
Denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell.
What does the term 'apoptosis' mean in Greek?
It refers to 'falling off.'
What is liquefactive necrosis?
It is the digestion of dead cells and the transformation of tissue into a liquid viscous mass.
What is the major mechanism of apoptosis?
The Intrinsic (Mitochondrial) Pathway.
What does cytopathology primarily focus on?
The examination of cells to identify abnormalities and diseases.
What stains are often used in histopathology?
Hematoxylin and eosin (H&E) stains.
What is the significance of understanding cellular responses to stress?
It helps in diagnosing and treating diseases related to cell injury and death.
What is apoptosis?
A regulated mechanism of cell death.
What contributes to the appearance of fibrinoid necrosis?
Deposits of immune complexes and fibrin that has leaked out of vessels.
How does apoptosis relate to neurodegenerative diseases?
Apoptosis is caused by mutations and misfolded proteins.
What are the first alterations in cell injury?
Molecular or biochemical level changes.
Where do the foci of fat necrosis typically occur?
In the mesentery.
What is a localized area of coagulative necrosis called?
An infarct.
What is general pathology focused on?
The common reactions of cells and tissues to injurious stimuli.
What are resection specimens?
Tissues or organs removed during surgery for diagnostic or treatment purposes.
What is the role of caspase-1 in pyroptosis?
It cleaves a precursor form of IL-1 and releases its biologically active form.
What are apoptotic bodies?
Fragments formed from the breakdown of apoptotic cells, making them edible for phagocytes.
What is bone classified as?
A type of connective tissue that provides structural support.
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 an example of cell loss in proliferating cell populations?
Loss of immature lymphocytes in the bone marrow and thymus.
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 do granzymes activate?
A variety of cellular caspases.
What maintains cell viability in the intrinsic pathway of apoptosis?
Induction of anti-apoptotic proteins such as BCL2 by survival signals.
What characterizes cell injury?
The cell is no longer able to adapt.
What are the pro-apoptotic proteins mentioned?
BAX and BAK.
What is the appearance of the area of necrosis in caseous necrosis?
Friable white appearance.
What type of biopsy involves removing a portion of a lesion?
Incisional biopsy.
What are the morphological changes associated with necrosis?
Damage to cell membranes, loss of ion homeostasis, and lysosomal enzymes digesting the cell.
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 changes occur in mitochondria during reversible cell injury?
Swelling and the appearance of small amorphous densities.
What happens to membrane integrity during necrosis?
There is no membrane integrity; contents often leak out, causing inflammation in the surrounding tissue.
What are proenzymes or zymogens?
Inactive forms of enzymes that undergo cleavage to become active.
In which conditions is liquefactive necrosis commonly seen?
In focal bacterial or fungal infections.
What is a characteristic feature of cell shrinkage in apoptosis?
The cell is smaller in size, and the cytoplasm is dense.
What is the significance of identifying cell types in histopathology?
It helps in diagnosing diseases and determining treatment options.
What causes the initiation of apoptosis in the intrinsic pathway?
Increased permeability of the mitochondrial outer membrane.
How are samples typically obtained for cytopathology?
Through fine needle aspiration, exfoliative cytology, or other sampling methods.
What is the purpose of apoptosis?
To eliminate unwanted and irreparably damaged cells.
What is necrosis?
A form of cell injury that results in the premature death of cells in living tissue.
What role does apoptosis play in autoimmune disorders?
Defective apoptosis leads to the survival of lymphocytes that can react against self antigens.
In which organs does coagulative necrosis occur due to ischemia?
In all organs except the brain.
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.
What effects does IL-1 have in the body?
Induces leukocyte recruitment and fever.
What change occurs to phosphatidylserine in apoptotic cells?
It flips from the inner leaflet to the outer layer of the membrane.
Why are resection specimens important?
They provide critical information for diagnosis, treatment planning, and understanding disease progression.
What does systemic pathology examine?
The alterations and underlying mechanisms in organ-specific diseases.
What is cartilage?
A flexible connective tissue found in various parts of the body.
Why is it important to eliminate potentially harmful self-reactive lymphocytes?
To prevent reactions against one’s own tissues.
What happens if the injurious stimulus abates in reversible cell injury?
The cell can repair the derangements and return to normalcy.
What detects misfolded proteins in the endoplasmic reticulum (ER)?
Sensors in the ER membrane, such as the kinase IRE1.
What role do genetic polymorphisms play in cellular responses to injury?
They influence the responses of different individuals to various injurious agents.
What is the role of anti-apoptotic proteins like BCL2?
They maintain the integrity of mitochondrial membranes and prevent leakage of mitochondrial proteins.
What triggers ferroptosis?
Excessive intracellular levels of iron or reactive oxygen species.
What may happen to cell injury over time?
It may progress through a reversible stage and culminate in cell death.
How do CTLs kill target cells?
By directly inducing the effector phase of apoptosis.
What do pro-apoptotic proteins promote?
Mitochondrial outer membrane permeability.
What is observed on microscopic examination of caseous necrosis?
Structureless collection of fragmented or lysed cells and amorphous granular debris.
What leads to cell injury?
A sequence of events including exceeded adaptive responses, exposure to injurious agents or stress, and deprivation of essential nutrients.
What are the visible signs of cellular swelling at the organ level?
Pallor, increased turgor, and increase in weight of the organ.
What triggers necrosis?
Ischemia, exposure to toxins, various infections, and trauma.
What type of tissue sample is used for cytopathology?
Aspiration materials and exfoliative cytology (smear).
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 initiates the Extrinsic (Death Receptor-Initiated) Pathway of Apoptosis?
Engagement of plasma membrane death receptors on various cells.
What enzymes contribute to the digestion of cellular contents during necrosis?
Enzymes from the lysosomes of dying cells and from leukocytes.
What causes the accumulation of leukocytes in liquefactive necrosis?
The liberation of enzymes.
What are the two phases of apoptosis?
The initiation phase and the execution phase.
What happens to chromatin during apoptosis?
Chromatin condenses and aggregates peripherally under the nuclear membrane into dense masses.
What types of diseases can cytopathology help diagnose?
Cancer, infections, and inflammatory diseases.
What is a key characteristic of apoptosis in terms of host reaction?
It results in the least possible host reaction.
What is increased eosinophilia in necrosis associated with?
The loss of cytoplasmic RNA and denatured cytoplasmic proteins.
What is apoptosis?
A programmed cell death process that occurs in a regulated manner.
What is released from the mitochondrial intermembrane space during apoptosis?
Death-inducing molecules such as cytochrome c.
How quickly can reversible morphologic changes, like cell swelling, occur?
In a matter of minutes.
Which caspase is closely related to caspase-1 and also induces cell death?
Caspase-11.
What role do soluble factors secreted by apoptotic cells play?
They recruit phagocytes to the site of cell death.
What types of conditions might require the examination of resection specimens?
Cancer, inflammatory diseases, and other pathological conditions.
What is the primary function of connective tissue?
To support, bind together, and protect tissues and organs.
What area of pathology studies diseases of the cardiovascular system?
Cardiovascular system pathology.
What characterizes irreversible injury and cell death?
Persistent or excessive injury, leading to a 'point of no return.'
