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59 Cards in this Set
- Front
- Back
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Def: General Pathology
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basic reactions of cells/tissues to stimuli underlying diseases
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Def: Etiology
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What is the cause of disease
Is it intrinsic (genetics) or acquired (infection) |
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Def: Pathogenesis
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mechanism underlying a disease
i.e. sequence of events in response to etiological agent |
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Adaptation
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Molecular pathogenesis that returns the cell to a new homeostasis
Includes: Hyperplasia Hypertrophy Atrophy Metaplasia Dysplasia Inability to adapt leads to cell injury |
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What are the mechanisms of cell death?
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Necrosis
Apoptosis Autophagy |
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Hyperplasia
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Increase in cell number often increasing organ size
Often linked to hypertrophy Due to hormonal, compensatory changes, persistent cell injury, or increased functional demand May lead to cancerous lesions |
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Cyclosporin A
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Immunosuppresent drug that causes gingival hyperplasia
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Hormonal changes causing Hyperplasia
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Pathologic hyperplasia due to excessive hormones or growth factors
i.e. Increase in estrogen causes increase in number of endometrial cells |
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Compensatory changes causing Hyperplasia
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Increase in mass of organ after damage/resection
Stem cells likely contribute i.e.Liver regeneration |
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Secondary polycythemia
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Type of Hyperplasia due to increased functional demand
Ability to exchange gases in lungs is challenged and oxygen carrying capacity is reduced So body increases the number of red blood cells to increase oxygen carrying capacity |
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What can cause Hyperplasia
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Hormonal changes
Compensatory changes Increased functional demand Persistent cell injury |
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Hypertrophy
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Reversible Increase in the cell size in stressed cells with low proliferative potential, such as nerves and muscles
often helps functional capacity Results in increased size of organ or tissue Often tied to hyperplasia Caused by physiological, hormonal or pathological changes |
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What is the cellular adaptation to hypertension?
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Hypertrophy
There is enlargement of the cardiac myocyte cells to increase mechanical effort (cardiac output) At some point, it becomes pathological when the cells become too large and block the ventricles |
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Hormonal hypertrophy
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Normal hypertrophy occurs during production of sex hormones during puberty
Exogenous hypertrophy occurs through the use of anabolic steroids Endogenous hypertrophy occurs through overproduction of TSH creating goiter |
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Atrophy
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Adaptive response to stress in which there is a decrease in cell size and function due to activation of autophagy and ubiquitin/proteasome pathway
Caused by decreased work load, diminished blood or nutritional supply, or chronic injury |
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Metaplasia
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Conversion of one differentiated cell type to another
Usually reversible Most common is conversion of columnar epi by squamous epi Caused by persistent injury or reprogramming of stem cells in adult tissue |
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What occurs to esophageal epi in GERD
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Barrett's Metaplasia
Esophageal epi undergoes metaplasia normal squamous epi lining of the esophagus is replaced by metaplastic columnar epi. |
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Epithelial Dysplasia
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Alter size, shape and organization of the cellular components of the tissue creating random cells
Causes by pre-neoplastic lesions or persistent injuries such as smoking or sunlight Often seen multiple nuclei |
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If you have increased demand or increased trophic stimulation by hormones, what type of cellular response would you expect
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Hyperplasia
Hypertrophy |
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If you have decreased nutrients or stimulation, what type of cellular response would you expect
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Atrophy
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If you have chronic irritation, either chemical or physical, what type of cellular response would you expect
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Metaplasia
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If you have acute reduced oxygen supply, what type cell injury would you expect
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Acute reversible injury
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If you have progressive and severe injury to the cell, including DNA damage, what do you expect the cell to undergo
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Irreversible injury leads to cell eath through Necrosis or Apoptosis
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What does a cell's response to injury depend on?
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On the type, duration and severity of the injury
Small amount of toxins or brief ischemia is not bad |
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What does the consequences of cell injury depend on?
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The type, state, and adaptability of the injured cells
Depending on cell type, the same stress can cause a different response |
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What occurs to the cell as the duration of injury increases?
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It goes from reversible cell injury to irreversible cell injury where there is biochemical alterations of the cells, then ultrastructural changes, than light microscopic changes and ultimately gross morphological changes to the cell.
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Hydropic Swelling
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Indication that the cells are stressed
It is an increase in cell volume characterized by large, pale cytoplasm and normal nucleus Cell is exposed to acute, reversible cell injury Due to lack of ATP which prevents Na/K ATPase from functioning, leading to accumulation of Na in the cell leading to increased water content Organ is heavier and firm |
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Ischemia
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Restriction of blood supply to the cells
Because of lack of oxygen, oxidative phosphorylation ends and glycolysis begins. There is decrease in ATP and increase in lactic acid production Na/K ATPase pumps stop and there is influx of Ca Leads to blebbing because of cellular swelling Clumping of nuclear chromatin because of decreased pH from lactic acid Decreased ATP causes cell injury but are reversible. Further depletion of ATP results in cell death by necrosis |
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Hypoxia
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Deficiency of oxygen
Causes cell injury by reducing aerobic oxidative respiration |
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Ischemia-reperfusion
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After loss of blood supply, restoration of blood flow induces additional cell death because of ROS generation, activation of complement by IgM antibodies and cytokines that induce inflammatory response
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What are the mechanisms of cell injury
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Mitochondria damage
decreased ATP production Entry of Ca2+ Increased ROS Membrane damage Protein misfolding, DNA damage These can all lead to cell death |
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What are some morphological patterns of necrotic pathology
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Coagulative necrosis
Liquifactive necrosis Caseous necrosis Fat necrosis Fibrinoid necrosis |
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Coagulative necrosis
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outline of the dead cells and architecture are maintained
tissue is somewhat firm Protein denaturation (low pH) is the primary pattern. Example: myocardial infarction |
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Liquifactive necrosis
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dead cells undergo disintegration and affected tissue is liquefied.
Due to bacterial or fungal infection Enzyme digestion of dead cells by leukocyte hydrolases Abscess if formed when cells are killed leaving a cavity filled with leukocytes called PUS Example: cerebral infarction or bacterial infection. |
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Caseous necrosis
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Form of coagulative necrosis in which the tissue maintains a cheese-like appearance
dead tissue appears as a soft and white proteinaceous dead cell mass. Example: tuberculosis lesions. |
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Fat necrosis
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enzymatic digestion of fat.
Example: necrosis of fat by pancreatic enzymes. Occurs when activated pancreatic lipases are released into pancreas. Causes white chalky deposits of calcium soap formation at sites of lipid breakdown |
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Fibrinoid necrosis
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Form of necrosis in which there is accumulation of amorphous, basic, proteinaceous material in the tissue matrix with a staining pattern reminiscent of fibrin
Occurs in blood vessel walls where the wall of the artery shows a circumferential bright pink area of necrosis with inflammation seen as neutrophils with dark nuclei |
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PUS
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Abscess formed when cells are killed and digested faster than the repair process, leaving a cavity filled with leukocytes
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Programmed Cell Death I
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AKA Apoptosis
Cell is Induced to commit suicide |
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Programmed Cell Death II
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AKA Autophagy
Cell is Starved to death |
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Programmed Cell Death III
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AKA Necrosis
Cell is Killed by injurious agents |
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Programmed Cell Death
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Three mechanisms through which the cells can die
Apoptosis, autophagy and necrosis There is cross-talk between the three mechanisms |
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Autophagy
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Relies on Ubiquitin-proteasome system to label proteins to be degraded
Form vacuoles which fuse with lysosomes to turn over mitochondria and proteins Lose differentiated function Linked to BCL-2 family of proteins |
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Necrosis
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The normal cell, in response to injury beings to swell.
Progressive injury causes the cell to continue to swell and the membrane blebs off causing the cell to pop There is leakage of the cells contents which triggers an immune response The process is not well controlled by the cell Due to trauma/poison/infection Loss of plasma membrane integrity is the first event |
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Apoptosis
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The normal cell, in response to injury begins to shrink.
The cell decreases in volume and the membrane begins to bleb off. Progressive injury leads to cellular fragmentation and release of apoptotic bodies which are eaten by macrophages No immune response is triggered Well controlled cell suicide Regulated by BCL-2 family of proteins and P53 Loss of plasma membrane integrity is the last event |
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What type of cell death is it when the loss of plasma membrane integrity is the first event?
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Necrosis
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What type of cell death is it when the loss of plasma membrane integrity is the last event?
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Apoptosis
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P53
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Guardian of the genome
If there is DNA damage, P53 detects it and tells the cell go into apoptosis Regulates BCL-2 family of proteins |
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What are the general characteristics of apoptosis
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Loss of lipid bilayer asymmetry
Nuclear shinrkage and DNA laddering Membrane blebbing Cell rounds up Loss of plasma membrane integrity |
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What are the key players in apoptosis
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Caspases (protease)
Endonucleases Mitochondria and BCL-2 family proteins (Intrinsic apoptosis) Death receptors in plasma membrane like Fas ligand and Tumor Necrosis Factor (extrinsic apoptosis) |
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Caspases
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Central executioners of apoptosis
Zymogen They are cystein proteases that cleave asp-xxx Approx 14 different kinds that recognize different things Cleaves other proteins like: CAD (Caspase-activated DNAase) triggers DNA laddering Gelsolin causes cytoplasm liquification PARP causes nuclear shrinkage PAK2 causes membrane blebbing |
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Endonucleases
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Activated by caspases to degrade DNA in apoptosis
Cleaves DNA and forms ladders on agarose gells DNA exists as perals ona string and endonucleases clip between the pearls (nucleosomes) Very orderly cleavage |
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What are the major players of intrinsic apoptosis?
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Caspases are cleaved to form active cysteine proteases
BCL-2 proteins regulate commitment to die Mitochondria compartmentalize pro and anti-apoptotic materia Endonucleases degrade DNA cleaving at nucleosomes |
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BCL-2
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Isolated from B cell Lymphoma
They govern mitochondrial outer membrane permeabilization Classified into 3 functional groups: I: Anti-apoptotic (Bcl-2, Bcl-xl) II: Pro-apoptotic (Bax) III: BH3 proteins that monitor DNA and signal when cell should die |
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Group II Bcl-2 proteins
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Pro-apoptotic proteins
Responsible for cytochrome C release Ex: Bax |
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What are the major players of extrinsic apoptosis?
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Death receptors that are activated by external stimuli
Ex: tumor necrosis factor and Fas ligand Cause cleavage of intrinsic procaspases |
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How do cells kill other cells by inducing apoptosis?
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Fas ligand generating cells kill cells that have Fas receptor by extrinsic pathway
Tumor necrosis factor is secreted by macrophages and binds to TNF receptors to induce extrinsic apoptosis Killer lymphocytes inject granzyme through perforin |
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What stimuli can trigger apoptosis?
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Differentiation of CD4 and CD8 T-cells
DNA damage ROS Growth factor withdrawal Lack of survival signals Viral infection |
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What features of apoptosis are essential to immune response?
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Cells autodigest including intracellular pathogens
Loss of plasma membrane integrity is the last step, so intracellular pathogens are destroyed before integrity is lost |
