Summary Class notes - Pathology

- Pathology
- dr. S. Amor
- 2021 - 2022
- Vrije Universiteit Amsterdam
- Gezondheid en Leven
635 Flashcards & Notes
1 Students
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Summary - Class notes - Pathology

  • 1612220401 Lecture 1 - Ch2: Cell injury, cell death and adaptations

  • Definition disease
    Dysfunction of an organ or tissue, because of damage to the cells
  • Definition etiology
    The underlying causes and modifying factors that are responsible for the initiation and progression of disease. For example the damaging agent.
  • Definition pathogenesis
    The mechanisms of development and progression of disease, which account for the cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize any particular disease
  • Definition adaptation
    The cell/organ reacts to minimize impact of damage. It achieves a new steady state and preserving viabilty and function.
  • What are the consequence of damage?
    1. It can be reversible
    2. Lead to adaption
    3. Lead to death of the cell 
  • Definition hypertrophy
    Increase in the size of cells, NO increase in number of cells.
  • What happens with myocardial hypertrophy?
    1. Mechanical stretch. Induction of embryonic genes. It increases the mechanical performance and decreases the work load. 
    2. Agonist. It increases the synthesis of contractile proteins and thereby increase the mechanical performance.
    3. Growth factors.  It increase the production of growth factors. 
  • Definition hyperplasia
    Hyperplasia is an increase in the number of cells in an organ that stems from increased proliferation, either of differentiated cells or, in some instances, less differentiated progenitor cells.
  • Definition atrophy
    Decrease of tissue by decrease of cell size and/or number
  • In which ways atrophy can occur?
    1. Autophagy
    2. Proteosomal degradation
    3. Apoptosis 
  • Definition metaplasia
    Metaplasia is a change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type
  • What happens where there is oxygen shortage?
    The cell swells because of failure of Na/K ATPase
  • Describe necrosis
    Progressive injury. First ER and mitochondria swell. Then there is breakdown of plasma membrane, organelles, and leakage. Necrosis occurs.
  • Describe apoptosis
    First there is condensation of chromatin and membrane blebs arise. Here cellular fragmentation arise and become apoptotic bodies. Then there is phagocytosis of the apoptic cells.
  • Which form of cell death is pro-inflammatory?
  • Which form of cell death is anti-inflammatory?
  • Definition coagulative necrosis
    Underlying tissue is preserved for several days after death of cells. The injury denatures proteins and enzymes, therefore blocking proteolysis of the dead cells.
  • Definition liquefactive necrosis
    Dead cells are completely digested and turned into liquid (pus).
  • Definition gangrenous necrosis
    Refers to the condition of a limb that has lost its blood supply and has undergone coagulative necrosis. This can turn into “wet gangrenous” with a bacterial infection (form of liquefactive necrosis)
  • Definition caseous necrosis
    “Cheese like” yellow-white appearance formed by a collection of fragmented or lysed cells. Mostly surrounded by macrophages
  • Definition fat necrosis
    Focal areas of fat destruction, resulting from the release of activated pancreatic lipases into the pancreas or peritoneal cavity.
  • Definition fibrinoid necrosis
    Complexes of antigens and antibodies are deposited in the walls of blood vessels, which occurs in immune reactions or hypertension.
  • When apoptosis occurs?
    • Embryonal development
    • Normal tissue homeostasis
    • Selection
    • Involution 
    • Termination of inflammatory response 
    • Elimination of virus-infected cells 
    • Elimination of stressed cells 
    • Elimination of damaged cells 
  • Triggers extrinsic apoptosis-induction
    A lethal signal from outside the cell (FasL, TNF) triggers through receptor activation a cascade that leads to apoptosis.
  • Describe the extrinsic apoptosis pathway
    1. Ligand binds
    2. Adaptor proteins bind via death domain and recruit and activate caspase-8
  • Triggers mitochondrial (intrinsic) pathway of apoptosis-induction
    • Lack of survival signals
    • Damage
    • Stress of cell 
  • Describe intrinsic pathway
    1. BH3 sensors the triggers
    2. It inactivates the Bcl-2 family 
    3. Activation of BAX/BAK channels
    4. Cytochrome C and other pro-apoptotic proteins leak out the mitochondria
    5. They activate caspase 9 
    6. Apoptosis 
  • What is the cause of follicular lymphoma?
    Loss op apoptosis-response by overexepression of BCL2-gen
  • What are the functions of cytochrome C?
    1. Electron transport in oxidative phosphorylation
    2. Induction apoptosis 
  • Function apoptosome
    It activate caspase-9.

    1. Cytochrome C binds to Apaf-1.
    2. The thus formed heptamere complex binds procaspase-9 and ATP
    3. Procaspase-9 is activated  and the cascade of caspase-activations ensues 
  • Describe the adaptive unfolded protein response
    Misfolded proteins leads to mild ER stress. IRE1 sensors this. This leads to: 

    1. Increased synthesis of chaperones
    2. Reduced protein synthesis
    3. Increased protein degradation

    In this way misfolded proteins are reduced 
  • Describe terminal unfolded protein response
    To much misfolded proteins lead to activation of BH3 proteins. This leads to apoptosis.
  • Definition euchromatin
  • Definition heterochromatin
    Silent DNa
  • Function phosphatidylserine (PS)
    It flops the external side of the cell membrane during apoptosis. Annexin V can bind to PS
  • Definition necroptosis
    A form of cell death initiated by engagement of TNF receptors. However, these receptors activate kinases called receptor-interacting protein (RIP), which results in dissolution of the cell, much like necrosis.
  • What are the mechanisms of intracellulair accumulations?
    1. Abnormal metabolism leads to fatty liver
    2. A mutation leads to defect in protein folding, and transport. This leads to accumulation of abnormal proteins.
    3. A deficiency of critical enzymes responsible for breaking down certain compounds, causing substrates to accumulate in lysosomes, as in lysosomal storage disease. 
    4. An inability to ingest indigestible materials. This leads to accumulation of exogenous materials. 
  • Function short telomere regions
    They induce a DNA damage response, that leads to an irreversible proliferation stop: cellular senescence.
  • What are the consequences of short telomeres?
    Forced proliferation. This leas to:

    • End-to-end joining of chromosomes
    • Chromosome breaks
    • Anueploïdie
    • Tumorigenese   
  • When cell injury develops?
    When the adaptive capability is exceeded or the external stress is inherently harmful or excessive.
  • What are the step in evolution of disease?
    1. Etiology 
    2. Pathogenesis
    3. Molecular, functional and morphological abnormalities. 
    4. Signs and symptoms of disease 
  • What are the causes of cell injury?
    1. Hypoxia 
    2. Toxins
    3. Infectious agents
    4. Immunological reactions 
    5. Genetic abnormalities 
    6. Nutritional imbalance
    7. Physical agents 
    8. Aging 
  • Definition reversible cell injury
    The stage of cell injury at which the deranged function and morphology of the injured cells can return to normal if the damaging stimulus is removed
  • What are the 3 characteristics of irreversible damage?
    1. Inability to restore mitochondrial function
    2. Loss of structure and functions of the plasma and intracellulair membrane
    3. Loss of DNA an chromatin structural integrity. 
  • Definition pyroptosis
    This form of cell death is associated with activation of a cytosolic danger-sensing protein complex called the inflammasome
  • Definition autophagy
    Refers to lysosomal digestion of the cells own components
  • What are reversible cell injuries?
    1. Cell swelling
    2. Fatty change
    3. Plasma membrane blebbing
    4. Loss of microvilli
    5. Mitochondrial swelling
    6. Dilation of the ER
    7. Eosinophila 
  • Where depends the cellular response on?
    Type, duration and severity of injury
  • Where depends the consequences of an injurious stimulus on?
    Type, status, adaptability and genetic make up of injured cell.
  • What is cell injury a result of?
    Functional and biochemical abnormalities in one or more of a limited number of essential cellular components.
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Summary - Class notes - Pathology

  • 1580684400 Lecture 1

  • What is a sign? What is an example?
    What you can see (e.g. Imbalance).
  • What is a symptom? What is an example?
    What you can't see (e.g. Nausea).
  • What are morphological manifestations?
    How the disease changes the tissue and organ that is affected.
  • What are functional manifestations?
    The consequences of the morphological manifestations.
  • What is relevant information about a disease?
    • Diagnosis
    • Prognosis
    • Prediction
  • 1580770800 Lecture 2

  • What is the difference between etiology and pathogenesis?
    Etiology is what causes the disease. Pathogenesis is what maintains the disease (= mechanism of disease).
  • What is the disadvantage of multicellular individuals?
    The internal milieu is optimized for functioning and thus attractive for intruders. Therefore, you need an effective defence.
    Organisation and clear division of tasks in mandatory and thus the replenishing of cells is needed (cell proliferation).
  • What is the difference between adaptation and cell death?
    Adaptation means that the cell adapts to a new situation. When a cell can no longer adapt it will die.
  • What is hypertrophy?
    The increase in size of cells.
  • What is hyperplasia?
    The increase in number of cells.
  • What is atrophy?
    The decrease of tissue by decrease of cell size and/or number
  • What is autophagy?
    Cells under poor conditions eat itself, they are taken up by lysosomes.
  • What is needed for proteasomal degradation?
  • What is apoptosis?
    Programmed cell death
  • What happens to apoptotic bodies?
    They are taken up by macrophages.
  • What is metaplasia?
    The replacement of one tissue by a (normal) other one.
  • What is Barret's metaplasia?
    Esophagus becomes more resistant to acid (refluxes). Stratified squamous epithelium changes into single columnar epithelium.
  • What happens if a cell swells? Why does this happen?
    If a cell swells this is because the Na-K-ATPase pump fails. Na will accumulate in the cell and this attracts water so the cell swells up.
  • What is coagulation necrosis?
    Necrosis in which the structure remains but cells are dead, there is no nucleus anymore.
  • What is colliquative necrosis? Where does this mainly happen?
    Necrosis in which the tissue dissolves, it becomes liquid. This mainly happens in the brain.
  • What is caseous necrosis? In which disease does this happen?
    Necrosis in which the tissue looks like cheese. This happens in tuberculosis.
  • What is fat necrosis? Where does this happen?
    Necrosis in which lipase releases fatty acids. This happens in the pancreas (pancreatitis).
  • What is fibrinoid necrosis?
    Necrosis that results in the formation of fibrous tissue.
  • What is the difference between necrosis and apoptosis?
    Necrosis means that the cell swells up and breaks down completely, with an inflammatory response.
    Apoptosis means that proteins are not released but taken up by macrophages, there is no inflammatory response.
  • What is the difference between the intrinsic and extrinsic pathway of apoptosis?
    The mitochondria (Bcl-2 family) is involved in the intrinsic pathway. The signal comes from inside the cell.
    The extrinsic pathway has a signal from outside the cell (FasL, TNF). The signal activates a receptor and a cascade leads to apoptosis.
  • What type of signals activate the intrinsic pathway of apoptosis?
    • Lack of survival genes
    • Damage
    • Stress
  • What is the apoptosome?
    The apoptosome activates caspase-9 which leads to apoptosis.
  • What is meant with ER stress? In which disease is this involved?
    Misfolded proteins accumulate in the ER. This can have different effects:
    • Trigger the caspase system, leading to apoptosis
    • Trigger degradation of the misfolded protein
    • Decrease protein synthesis 

    This process is involved in neurogenerative diseases, such as dementia.
  • What happens to a cell when it gets older?
    A cell undergoes telomere-shortening and this means that the cell is no longer able to divide.
  • How can telomerase be made?
    By telomerase
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What is the most dominant type of tumor that metastasize into the nervous system?
With what increasing tumor malignancy is associated?
It is associated with more cytologic anaplasia, increased cell density, necrosis, and mitotic activity
From where CNS tumors arise?
Tumors of the CNS may arise from the cells of the coverings (meningiomas), the brain (gliomas, neuronal tumors, choroid plexus tumors), or other CNS cell populations (primary CNS lymphoma, germ cell tumors), or they may originate elsewhere in the body (metastases)
In which groups astrocytomas as grouped?
diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV), with increasingly grim prognosis as the grade increases.
Definition MS
MS is an autoimmune demyelinating disorder characterized by episodes of disease activity, separated in time, that produce white matter lesions that are separated in space
In what infectious meningtis can be grouped?
  • Acute pyogenic
  • Aseptic
  • Chronic 
Definition meningitis
Meningitis is an inflammatory process involving the leptomeninges within the subarachnoid space;
Which infections occur mostly in epidural en subdural spaces?
Bacterial and fungal infections. Usually as a consequences of direct local spread.
What are the major injuries that occur in perinatal period?
Hemorrhages and infarcts
What leads to malformations?
Partial failure or reversal of neural tube closure may lead to several malformations, each characterized by abnormalities involving neural tissue, meninges, and overlying bone or soft tissues