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120 Cards in this Set
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ETIOLOGY (causes) OF CELL INJURY
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Ischemia/Anoxia-hypoxia
Physical, chemical and biologic agents Immune reactions Genetic derangements Nutritional imbalance Aging |
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CELLULAR ADAPTATION
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• Atrophy: Decrease in cell size due to decrease in structural components of the cell (mitochondria, myofilaments and endoplasmic reticulum)
• Hyperplasia (increase in the number of cells) • Hypertrophy (increase in cell size) • Metaplasia (change from one adult cell type to another adult cell type as a result of reprogramming of stem cells) |
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Examples of pathologic atrophy
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Reduced functional activity and/or prolonged pressure
Loss of innervation Reduced blood supply Insufficient nutrition Loss of hormones and/or cytokines/growth factors |
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Examples of pathologic hyperplasia
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Hormone hyperactivity (Cushing’s syndrome, nodular prostatic hyperplasia)
Autoimmune mechanisms (psoriasis vulgaris, Graves’ disease) Viral infection (warts) Inflammation and wound healing (keloids) |
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Examples of pathologic hypertrophy
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Cardiac hypertrophy (systemic hypertension, restricted aortic outflow due to aortic valve stenosis)
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Examples of pathologic metaplasia
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Squamous cells in trachea of smokers
Glandular cells in stomach (Gastric ulcer) or esophagus (Barretts) Connective Tissue - fibroblasts into osteoblasts chondroblasts (surg scars) |
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Reversible Cell Injury
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Cell Swelling (Hydropic or Vacuolar Degeneration)
Fatty Change (Alcoholics) |
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Irreversible Cell Injury
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Severe trauma and/or longer duration of injury cause irreversible lesions and cell death:
• Necrosis (also defined as “accidental cell death”, cell death with swelling or “oncosis”) • Autophagy • Apoptosis (also defined as cell death with shrinkage or “programmed cell death”). |
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• A 33-year-old patient presents with nausea and jaundice, possibly caused by infection with hepatitis A virus. Serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) are much higher than reference values. Discuss the pathogenesis of the increase in serum enzyme levels.
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Prob necrosis - enzymes leaking out indicate cell death by necrosis
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• A 72-year-old patient falls down and fractures the left leg. After several weeks in a cast the diameter of the left calf decreases considerably. Define this process and explain its pathogenesis.
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Example of pathologic atrophy
(Reduced functional activity and/or prolonged pressure) |
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• Discuss the role of hypoxia-inducible factor (HIF) and possible therapeutic applications of HIF agonists.
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Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment, specifically, to decreases in oxygen, or hypoxia. Hypoxia often keeps cells from differentiating. However, hypoxia promotes the formation of blood vessels, and is important for the formation of a vascular system in embryos. The hypoxia in wounds also promotes the migration of keratinocytes and the restoration of the epithelium
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Describe one possible cause of metaplasia.
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When cells are faced with physiological or pathological stresses, they respond by adapting in several ways; one of these cellular adaptations is metaplasia. It is a benign (i.e. non-cancerous) change that occurs as a response to chronic physical or chemical irritation, such as cigarette smoke that causes the mucus-secreting ciliated simple columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium, or a stone in the bile duct that causes the replacement of the secretory columnar epithelium with stratified squamous epithelium (Squamous metaplasia)
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The removal of microorganisms and tissue debris by the inflammatory process represents a key step in the ultimate healing process by allowing repair to proceed in the form of ...
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Granulation tissue
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Is composed of leukocytes (usually macrophages and lymphocytes), new blood vessels, as well as fibroblasts..
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Granulation tissue
again |
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A parasitic disease caused by several species of tremotodes ("flukes"), a parasitic worm of the genus Schistosoma..
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Schistosomiasis
Although it has a low mortality rate, schistosomiasis often is a chronic illness that can damage internal organs and, in children, impair growth and cognitive development. The urinary form of schistosomiasis is associated with increased risks for bladder cancer in adults. Schistosomiasis is the second most socioeconomically devastating parasitic disease after malaria. |
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Hallmarks of Chronic Inflammation
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Mononuclear leukocyte
Macrophages and lymphocytes (both T and B cells), as well as macrophage-derived cells (i.e., the epithelioid and the giant cell). Although all these cells are hallmarks of chronic inflammation, not all chronic inflammatory processes will have all the cells present, nor will the proportions of the cells be similar. |
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When chronic inflammation causes complete tissue destruction within tissues it is referred to as...
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An abscess
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Lymphocytes that produce the T1 class of cytokines (e.g. Interferon, TNF, IL-12) promote...
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Macrophage activation and thus promote delayed type hypersensitivity (DTH) which increases macrophage activation, inflammation and tissue destruction.
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Alternatively lymphocytes that produce T2 cytokines (e.g. IL-10, IL-4, GMCSF etc) tend to
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suppress macrophage activation and thereby suppress inflammation and tissue destruction.
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Histologically granulation tissue is characterized by .
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presence of sparse mononuclear leukocytes, neovascularization, fibroblasts, and in some cases fibrosis (collagen deposition).
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The factors that are important in determining regeneration versus fibrosis are:
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1) the nature of the cells that are at the tissue site, the extent of the inflammatory reaction, and 2) whether or not basement membranes are destroyed as a consequence of the inflammatory process.
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Three broad types of cells:
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labile cells, stable cells and permanent cells.
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The process of fibrosis has five major steps:
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1) angiogenesis, 2) migration of fibroblasts, 3) proliferation of fibroblasts, 4) deposition of extracellular matrix, and 5) remodeling of the fibrous tissue. These five steps form the heart of fibrosis.
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Histologically granulation tissue is characterized by .
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presence of sparse mononuclear leukocytes, neovascularization, fibroblasts, and in some cases fibrosis (collagen deposition).
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factors that control the movement of fluid, as well as the vasculature that controls the fluid are called...
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vasoactive factors
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Factors controlling white blood cell movement and activation are often referred to as...
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leukoactive factors.
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Kinin System
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Kinins are small molecular weight peptides released from plasma zymogen proteins such as a bradykinin, kininogen, etc. by specific proteases present both in the plasma, as well as in leukocytes. Kinins represent extremely potent vasoactive substances and show action similar to histamine (i.e. increased vasopermeability, vasodilation, vasoconstriction and pain). Prototypic example of a kinin is bradykinin, which is extremely potent vasoactive peptide derived from high molecular weight kininogen.
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What do these the following have in common
platelet-activating factor, arachadonic acid metabolites, and prostaglandins |
Class of mediators derived from the phospholipids
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Histamine, which is present in mast cells, has the capability to act as a vasoactive substance by inducing
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1) contraction of smooth muscles, 2) arterial dilation, and 3) post-capillary leakage (increased permeability). Additionally, histamine has the capability to directly induce pain through nerve endings.
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Besides Histamine, what other substance is released from mast cells? What can it do that histamine can't?
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Serotonin or 5-hydroxytryptamine (5HT) is found primarily in platelets, and is released upon platelet aggregation. Serotonin shares the same vasoactive capabilities with histamine, but also has the capability to activate fibroblasts in fashions not seen by histamine.
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What are C3a and C5a?
How do they act differently from C3b |
Regardless of the mechanism of activation, the activation of the complement system results in the generation of a wide variety of inflammatory mediators which control the movement of both fluids and cells during inflammation, i.e. the generation of vasoactive and chemotactic factors (e.g., C3a and C5a). Additional activation of the complement system results in the appearance of opsonins (e.g., C3b) which are important in enhancing host defense by increasing leukocyte function, e.g. phagocytosis.
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What is the difference between the classic and alternative pathway of complement activation?
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Mechanistically, the complement system can be broken into two pathways, the classical pathway, which is activated by immune complexes, and the alternative pathway, which is activated non-specifically, generally by the presence of specific negatively charged surfaces such as bacterial membranes.
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Type of necrosis in MI?
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Coagulative
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Type of Necrosis in CNS
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Liquefactive
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Type of Necrosis in Lung with TB?
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Caseous
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Type of Necrosis in Acute Pancreatitis?
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Enzymatic Fat Necrosis
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What are the 5 key characteristics of necrosis?
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• A process affecting groups of cells (that die together)
• Never physiological, but caused by hypoxia, complement, toxins, etc. • Usually results in inflammation • Easy to detect in H&E-stained sections • EM: Cell membrane disruption, cellular swelling, irregular chromatin clumping and eventual lysis of chromatin (loss of nuclei) |
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Etiology of necrosis
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• Ischemia/anoxia-hypoxia
• Physical agents • Chemical agents • Biologic agents • Immune reactions • Nutritional imbalance • Genetic changes |
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Pathogenesis of necrosis
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• Loss of selective permeability of plasma membrane
• Loss of calcium homeostasis • Mitochondrial damage • Depletion of cellular ATP |
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Morphologic patterns of necrosis
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• Coagulative necrosis
• Liquefactive necrosis • Caseous necrosis • Fat necrosis |
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What is HMGB1?
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In the context of necrosis, it serves as a DAMP, a Damage Associated Molecular Pattern. Uric acid is another example.
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What makes up the inflammasome ?
What does it do? |
NOD-like receptors make it up. It a complex receptors for DAMPs An inflammasome is a caspase-1-activating multiprotein complex.
When caspase-1 (ICE) is activated, it mediates inflammation because it cleaves the pro-forms of IL-1B and IL-18, which in turn trigger other proinflammatory cytokines (IFN-gamma, TNF-A, chemokines, etc.) |
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What happens to apoptotic cells?
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Apoptotic cells are rapidly phagocytized by neighboring cells
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What are ultra structural characteristics of apoptosis?
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EM: Cell membrane intact, cellular shrinking, dense crescent-shaped chromatin aggregates, no mitochondrial alterations
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Etiology of pathologic apoptosis
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• Ischemia/Anoxia-hypoxia
• Physical agents (heat, x-rays, UV) • Chemical agents • Biologic agents (e.g., HIV) • Immune reactions (e.g., cytokines, CTL) • Nutritional imbalance (absence of growth factors) • Genetic changes |
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Pathogenesis of apoptosis
Intrinsic Pathway |
• Intrinsic pathway: Ischemia etc. permeabilization of mitochondrial outer membrane release of cytochrone c formation of apoptosome caspase cleavage apoptotic substrates
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Pathogenesis of apoptosis
Extrinsic Pathway |
• Extrinsic pathway: Fas ligand + CD95 adaptors caspase cleavage apoptotic substrates
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Give three example of disease processes that have both apoptosis and necrosis.
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Infarction of brain
Myocardial infarction Acute viral hepatitis |
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What is the pathophysiology of loss of apoptosis in cancer cells?
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Too much BCL-2 production in leukemias.
• Anoikis (“homelessness”) and metastasis |
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What are Councilman bodies
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They represent hepatocytes that are undergoing apoptosis (controlled cell death).
Councilman bodies are eosinophilic globule often found in the liver of individuals suffering from viral hepatitis, yellow fever, or other viral syndrome. They are also seen in acute viral hepatitis. |
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What is Anoikis?
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Anoikis is a form of programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix (ECM). Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, i.e. there is a loss of normal cell-matrix interactions, they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.
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Which molecules of apoptotic cells are recognized by neighboring phagocytic cells?
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Phosphatidylserine expression on apoptotic cells are important for phagocytosis by NEARBY cells – even like epithelial cells!
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Which molecules of apoptotic cells are recognized by neighboring phagocytic cells?
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Phosphatidylserine expression on apoptotic cells are important for phagocytosis by NEARBY cells – even like epithelial cells!
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Virchow's Triad
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Hypercoagulability
Endothelial Dysfunction or Injury Stasis or Turbulence |
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Rank the following venous areas in order from highest to lowest probability of thrombus formation.
calf femoral popliteal iliac veins |
1.calf
2. femoral 3. popliteal 4. iliac veins |
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What is Thrombocytopenic purpura (TTP)?
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It is an occulsive microvascular disease, caused by a defected in the ADAMTS13 gene that encodes a protein which cleaves Von Villebrand Factor.
Typical skin lesions include petechiae and purpura. |
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What is hemolytic uremic syndrome?
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A disease characterized by hemolytic anemia, acute renal failure (uremia) and a low platelet count (thrombocytopenia). It predominantly but not exclusively affects children. Most cases are preceded by an episode of diarrhea caused by E. coli O157:H7, which is acquired as a foodborne illness. It is a medical emergency and carries a 5–10% mortality; of the remainder, the majority recover without major consequences but a small proportion develop chronic kidney disease and become reliant on renal replacement therapy. HUS was first defined as a syndrome in 1955.
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What is the pathogenesis of DIC?
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Pathogenesis: release of high levels of tissue factor into the circulation and/or endothelial cell injury
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What protein is involved in organ dysfunction and what organs are affected in DIC?
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Fibrin thrombi in brain, heart, lungs, kidneys, adrenals, spleen, liver, etc (no tissue is spared)
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What complications can follow DIC?
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Obstetric complications
Malignant Neoplasia Sepsis Major Trauma |
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What is an embolism?
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• Occlusion of some part of the vascular system caused by the impaction of material brought there by the circulation.
• Emboli can be solid, liquid and gaseous. • Emboli arising within most veins (usually deep veins of the legs and deep pelvic veins) travel centrally to the lungs and stop there (pulmonary embolism). • Emboli arising within the veins of the portal system travel to the liver. • Emboli arising in arteries travel peripherally and get stuck in a narrower part of the arterial bed. • Rarely, an embolus may cross from one side of the heart to the other when there are septal defects ("paradoxical embolus"). |
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What is an embolism?
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• Occlusion of some part of the vascular system caused by the impaction of material brought there by the circulation.
• Emboli can be solid, liquid and gaseous. • Emboli arising within most veins (usually deep veins of the legs and deep pelvic veins) travel centrally to the lungs and stop there (pulmonary embolism). • Emboli arising within the veins of the portal system travel to the liver. • Emboli arising in arteries travel peripherally and get stuck in a narrower part of the arterial bed. • Rarely, an embolus may cross from one side of the heart to the other when there are septal defects ("paradoxical embolus"). |
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Define Ischemia
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• Lack of blood or insufficient flow of blood.
• The most common cause of ischemia is arterial obstruction (thrombosis, embolism, and intrinsic arterial diseases such as atherosclerosis). |
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Infarction
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• Cell death due to an impaired supply of blood and/or oxygen.
• An infarct is a localized area of necrosis (and apoptosis). • The lack of blood causes necrosis (and apoptosis) of parenchymal cells, stroma and blood vessels in the area; edema and hemorrhage. |
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Arterial vs Venous Thrombi
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Arterial thrombi are frequently occlusive and are produced by platelet and coagulation activation; they are typically a friable meshwork of platelets, fibrin, erythrocytes, and degenerating leukocytes. Although arterial thrombi are usually superimposed on an atherosclerotic plaque, other vascular injury (vasculitis, trauma) can be involved.
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Venous thrombosis (phlebothrombosis) is almost invariably occlusive, and the thrombus can create a long cast of the lumen; venous thrombosis is largely the result of activation of the coagulation cascade, and platelets play a secondary role. Because these thrombi form in the sluggish venous circulation, they also tend to contain more enmeshed erythrocytes and are therefore called red, or stasis, thrombi. The veins of the lower extremities are most commonly affected (90% of venous thromboses); however, venous thrombi can occur in the upper extremities, periprostatic plexus, or ovarian and periuterine veins; under special circumstances they may be found in the dural sinuses, portal vein, or hepatic vein.
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What are lines of Zahn?
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Thrombi can have grossly (and microscopically) apparent laminations called lines of Zahn; these represent pale platelet and fibrin layers alternating with darker erythrocyte-rich layers. Such lines are significant only in that they represent thrombosis in the setting of flowing blood; their presence can therefore potentially distinguish antemortem thrombosis from the bland nonlaminated clots that occur in the postmortem state (see also below).
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What is a mural thrombi?
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Thrombi occurring in heart chambers or in the aortic lumen are designated mural thrombi. Abnormal myocardial contraction (resulting from arrhythmias, dilated cardiomyopathy, or myocardial infarction) or endomyocardial injury (caused by myocarditis, catheter trauma) promotes cardiac mural thrombi, while ulcerated atherosclerotic plaques and aneurysmal dilation promote aortic thrombosis.
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What is the pathogenesis of liquefactive necrosis in the CNS?
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On microscopic examination the tissue reaction evolves along the following sequence: After the first 12 hours, ischemic neuronal change (red neurons; see earlier) and both cytotoxic and vasogenic edema predominate. There is loss of the usual tinctorial characteristics of white- and gray-matter structures. Endothelial and glial cells, mainly astrocytes, swell, and myelinated fibers begin to disintegrate. Up to 48 hours, neutrophilic emigration progressively increases and then falls off. Phagocytic cells, derived from circulating monocytes and activated microglia, are evident at 48 hours and become the predominant celltype in the ensuing 2 to 3 weeks. The macrophages become stuffed with the products of myelin breakdown or blood and may persist in the lesion for months to years. As the process of liquefaction and phagocytosis proceeds, astrocytes at the edges of the lesion progressively enlarge, divide, and develop a prominent network of cytoplasmic extensions.
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8. A patient with severe coronary atherosclerosis is treated with percutaneous transluminal coronary angioplasty and, a coronary stent. After a few months of treatment with clopidogrel, a powerful antiplatelet drug used to prevent thrombosis after stenting, the patient develops autoantibodies against ADAMTS13 (a rare event, with an incidence rate of 1-3 per million). What are the possible consequences of this autoimmune response?
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Von Willebrand factor-dependent platelet adhesion and aggregation
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How do glucocorticoids reduce inflammation?
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Decreased IL-1, TNF which are proinflammatory
Decreased IL-12 and interferon Y important inducers of TH-1 cell activity and cellular immunity Inhibits phospholipase A2 reducing PG and leukotrienes Reduce expression of COX-2 Decrease capillary permeability by reducing histamine |
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Give two mechanisms to block leukotriene effects..
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Inhibition of 5-lipoxygenase
Leukotriene-receptor antagonist |
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PG Synthase – 1 (COX1) is found where? What are its functions?
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Expressed in most cells
“Housekeeping Functions” Gastric cytoprotection Platelets Renal Function |
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PG Synthase – 2 is known as inducible or non inducible?
What cells can express it? How do these cells know when to produce it? COX is is the primary source of vascular ___________________. |
Inducible
Expression is stimulated in macrophages/ monocytes and tissues by mediators of inflammation Primary source of vascular prostacylin Expressed in kidney |
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What are the vascular and platlet effects of TXA2
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Vascular: Constriction
Platet: Aggregation |
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What are the vascular and platlet effects of PGI2?
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Vascular: Dilation
Platlet: Inhibits aggreation |
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Why should you be concerned about asthma patients taking NSAIDS?
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1-5% of asthma patients have experienced NSAID induced exacerbated symptoms.
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HOWEVER they CAN be desensitized to it by starting with a very low dose aspirin and albuterol therapy.
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Name the mechanisms of PGE2 cytoprotection.
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Stimulation of mucin secretion by epithelial cells
Stimulation of bicarbonate by epithelial cells Enhancement of mucosal blood flow and oxygen delivery to epithelial cells |
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How do PGE2 and PGI2 affect the kidney?
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Dilate afferent artery
Increase sodium and water excretion (almost like a diuretic) |
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What is the difference between low dose and high dose aspirin?
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Low dose 81mg COX1 inhibitor (decreased TXA2) but higher dose inhibits both COX1 and COX2
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How long does aspirin exert its effect on platlets?
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For its lifetime
It IRREVERSIBLY inhibits platelet COX1 so decreases platelet function and prolongs bleeding time |
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What are some effects of ASA toxicity?
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Anion gap metabolic acidosis
Primary respiratory alkalosis Tinnitus/hearing loss Adult respiratory distress syndrome Decreased mental status |
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Whats an alternative to NSAIDS?
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Non acetylated salicylates
Anti-inflammatory but not due to prostaglandin inhibition Possible mechanisms Inhibit chemotaxis Inhibit neutrophil aggregation/activation Decrease proinflammatory cytokines |
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What effect do non acetylated salicylates have on platlets and the GI system?
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NONE!
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What does antipyretic mean?
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Antipyretics (literally "against the fire") are drugs that reduce fever.[ They will not normally lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature. The body will then work to lower the temperature and the result is a reduction in fever.
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Do COX2 specific and Non Acetylated Salicylates irreversibly inhibit platlet aggregation?
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No, they do not irreversibly inhibit platelet aggregation.
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Name adverse cardiovascular effects of ASA.
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ALL increase risk of cardiovascular events (particularly COX2 inhibitors) due to balance between inhibition of PGI2 and TXA2
Hypertension is secondary to Na retention and loss of vasodilation from PGI2 (remember PGI2 acts as a dilator and has diuretic like effects) |
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How do NSAIDS affect peoples' kidney's and why is it especially dangerous for people who are hypovolemic?
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Loss of PGE2 vasodilating effect on afferent artery leads to unopposed vasoconstriction and decreased kidney function.
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What is papillary necrosis?
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Renal papillary necrosis is a form of nephropathy involving the necrosis of the renal papilla, which is supplied by the vasa recta.
Analgesic nephropathy is a cause of renal papillary necrosis.[2] The damage is cumulative and most patients of renal papillary necrosis would have ingested at least 20kg of analgesics in the past. The risk is higher for phenacetin and acetaminophen compared to aspirin and other NSAIDs. Combination analgesic products, such as Goody's, also have a high risk of causing papillary necrosis. |
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Interstitial nephritis
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Interstitial nephritis (or Tubulo-interstitial nephritis) is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules. This disease can be either acute, meaning it occurs suddenly, or chronic, meaning it is ongoing and eventually ends in kidney failure.
Common causes include infection, or reaction to medication (such as an analgesic or antibiotics such as methicillin). Reaction to medications causes 71% to 92% of cases. |
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Glucocorticoids effects
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Decrease extravasation and infiltration of leukocytes into affected tissue and increase bone marrow release
Decreased lymphocytes in tissues due to migration to lymphoid tissue Inhibit the function of tissue macrophages and other antigen presenting cells Decreased IL-1, TNF which are proinflammatory Decreased IL-12 and interferon Y important inducers of TH-1 cell activity and cellular immunity Inhibits phospholipase A2 reducing PG and leukotrienes Reduce expression of COX-2 Decrease capillary permeability by reducing histamine |
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Glucocorticoids side effectts
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Hyperglycemia
Myopathy Hypertension Osteoporosis Bruising Fat redistribution Cataracts Peptic ulcers Infections (mainly decreased cellular immunity) Adrenal suppression |
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Effects of Leukotrienes
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Blood cells and inflammation
Chemoattractant for PMNs, eosiniphils and monocytes Eosiniphil adherance, degranulations and oxygen radical formation Implicated in the pathogenesis of inflammation especially in asthma Airways Potent bronchoconstrictors and increased microvascular permeability, plasma exudation and mucus secretion |
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How does chronic granulomatous inflammation differ from chronic diffuse
inflammation? |
Diffuse inflammation is spread throughout the tissue; however, chronic granulomatous inflammation involves localized patches. It also only involves the Macrophages pretty much and doesn’t involve gaint cells and epitheloid cells.
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Generally, why does chronic granulomatous inflammation rather than chronic diffuse inflammation develop?
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Generally, chronic granulomatous occurs because the macrophages are unable to breakdown the material – thus the only safe way of getting rid of it is to block if off from the rest of the body. Thus, it will link up w/ other macrophages and join together; although they lose their phagocytotic effect, they induce mad cytokines and you have epitheloid cells which will go around them and block them off. Regardless of the granulomas' type, granulomas arise when the offending initiating stimulus is difficult to digest and persists. This can be because the initiator is inert such as talc, or because the microbe is hard to digest because of its biochemical make up such as the mycoplasma tuberculosis.
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Do all granulomas look the same morphologically?
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No, there are inflammatory vs foreign body granulomas which look different. In foreign body granulomas you may see the foreign body that caused the granuloma to occur?
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Give examples of foreign body granulomas?
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Starch (Maltese cross birefringence in polarized light)
Talc - birefringent Suture material - (nylon, silk, dacron)- birefringent refractile multicoloured. Wood splinter or bone fragment- Special stains for microorganisms should be performed to rule out infection due to contamination. Plant material can be identified by PAS stain Arthropod bite can cause granulomatous reaction Silica (glass or sand ), zirconium & beryllium elicit sarcoidal granulomatous reaction. Tattoo material- Extracellular pigment is identified and may induce local sarcoidal granulomas. Tetanus toxoid (aluminium-adsorbed vaccines) may induce foreign body reaction. |
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What is the histological appearance of a prototypic granulomata seen
in a patient with TB? |
Caseous – giant cells, it’s an immune granuloma. And you will see caseous necrosis. Will see T cells around the graunoluma. Will see necrosis as well.
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What is the histological appearance of a prototypic foreign body granuloma?
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The prototype for foreign body granulomas are the granulomas seen in reaction to cholesterol crystals or sutures.
In small foreign body granulomas, often the granuloma only consists of a few multinucleated giant cells. Well developed foreign body granulomas will exhibit epithelioid cells, multinucleated giant cells, a variable number of lymphoid cells and fibrosis. |
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What is a multinucleated giant cell?
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It’s a combination of macrophages that fused together to trap a particle and they don’t phagocytosize and they pool their bacterocidal shit and cytokines.
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What are some of the most common granulomatous diseases
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TB,, Sarcodosis.
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What material in the workplace/environment can lead to pulmonary/systemic granulomatous disease?
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silica, TB,
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Why do surgeons now use cornstarch rather than talc on their rubber gloves?
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Talc can cause a granoluma, corn starch can be broken down.
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Define exudate and transudate
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Transudate is a fluid with low specific gravity (< 1.015), low protein content and few cells
- Characteristic of edema resulting from heart failure or other conditions without changes in capillary permeability so basically only water comes through Exudate is a fluid with high specific gravity (> 1.020), high protein content (more than 3%) and many red and white cells. - Characteristic of edema resulting from increased capillary permeability, as observed in inflammatory processes |
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Describe “nutmeg” liver and its pathogenesis (passive hyperemia)
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The liver is again enlarged and takes a characteristic appearance. It's called nutmeg liver because it's got an exaggerated lobular pattern due to congestions of the sinusoids. In mid zone and central lobular regions you have fatty change and necrosis of hepatocytes. Nutmeg liver - cytosol is red. Engorgement of blood vessels with red cells. As a consequence of cell death and fatty change there would be fibrosis and deposits of hemosiderin (because red cells die, release hemoglobin, gets metabolized, gets into macrophage), and Kupffer cells in the liver have that function.
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What is the pathogenesis of septic shock?
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Overwhelming microbial infections (70% due to gram negative bacilli expressing endotoxin/LPS): resulting in peripheral vasodilation and pooling of blood; endothelial activation and injury; leukocyte-induced damage; disseminated intravascular coagulation; activation of cascades
- systemic vasodilation (hypotension) - decreased myocardial contractility - widespread endothelial injury and activation, with systemic leukocyte adhesion and pulmonary alveolar capillary damage - activation of the coagulation system, culminating in DIC (disseminating intravascular coagulationbleeding/hemorrhage results) The resulting hypoperfusion causes multiorgan system failure affecting the liver, kidneys, and CNS. |
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What is the cause of cardiogenic shock?
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Cardiogenic: (decreased CO) myocardial infarction, ventricular rupture, arrhythmia, cardiac tamponade, pulmonary embolism
Shock is systemic hypoperfusion resulting from reduction in either cardiac output (CO) or the effective circulating blood volume (ECV). This reduction results in hypotension, followed by impaired tissue perfusion and cellular hypoxia. |
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What is dependent edema?
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Edema distribution is typically influenced by gravity and is termed dependent. Edema of the dependent body parts of the body (eg- legs when standing, the sacrum when recumbent) is a prominent feature of CHF.
Edema Distribution Dependent Edema (fluid shift in response to gravity) Standing patient accumulates fluid in feet and ankles Bed-bound patient collects fluid posteriorly (sacrum) A detectable increase in extracellular fluid volume localized in a dependent area such as a limb, characterized by swelling or pitting. |
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Define “ecchymosis”
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Larger than 1-2 cm; subcutaneous hematoma (typically seen after trauma)
Red blue color changes to blue-green color and eventually into gold-brown color A small, flat, hemorrhagic patch, larger than a petechia, on the skin or mucous membrane. Petechiae, purpura, and ecchymosis do not blanch (become pale) with pressure, while the redness of erythema decreases and then returns when pressure is applied and released. |
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Define petechiae
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Bleeding that consists of pinpoint dots of blood is called petechiae.
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Define purpura
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Larger flat areas where blood has collected under the tissue, up to a centimeter in diameter, are called purpura. A very large area is called an ecchymosis.
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IgG and IgM antibodies directed against epitopes present on the cell surface may kill cells by:
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• promoting phagocytosis
• activating phagocytes through their Fc receptors • promoting complement-mediated lysis |
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IgG antibodies to receptors can:
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• stimulate cellular function (agonist: e.g., hyperthyroidism of Graves’ disease)
• inhibit cellular function (antagonist: e.g., decreased muscle function in myasthenia gravis) • decrease cell surface receptors (inhibit function: e.g., decreased muscle function in myasthenia gravis) |
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Type II: Specific IgG antibodies may bind to hormones, enzymes, cytokines and toxins, When bound...
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they inhibit (“neutralize” or “block”) the function of these substances
• On the other hand, some antibodies to cytokines act as protectors and may carry them to other locations distant from the site of production |
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What is the pathogenesis of pemphigus vulgaris?
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Type II Hypersensitivity
Antibodies binding to desmogleins (epitopes in desmosomes of epithelial cells): they cause splitting of epithelia and blister formation, resulting in a disease called “pemphigus vulgaris” |
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What is the pathogenesis of GoodPasture's syndrome?
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Type II Hypersensitivity
Antibodies binding to epitopes of basement membranes in kidneys and lungs (noncollagenous domain of the alpha-3-chain of collagen IV): they activate complement, resulting in inflammation and cell injury (“Goodpasture syndrome”). |
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What are the most commonly employed ways to detect circulating antibodies?
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• ELISA (enzyme linked immunosorbent assay)
• Immunoblotting (Western blotting) • Agglutination of red cells (e.g., antihuman globulin test) |
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Difference between immune complex formation at subepithelial, subendothelial and mesangial sites.
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• Immune complexes in mesangial or subendothelial sites lead to recruitment of inflammatory cells, with subsequent inflammatory changes (e.g., nephritis). In contrast, circulating inflammatory cells do not have access to subepithelial immune deposits (no inflammation). In that case, kidney damage is caused by non-inflammatory mechanisms (e.g., membranous nephropathy)
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How do we detect immune complexes in human biopsies?
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Direct immunofluorescence (DIF)
With DIF we can demonstrate immune deposits (and not immune complexes) in biopsies of patients’ kidneys, skin, etc. |
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What are three functions of LPS?
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LPS is on Gram Neg Bacterial
It has antigenic and anti-phagocytic properties Finally, it can cause tissue damage because LPS is an endotoxin. |
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What are exoproteins? Name three pathways in which they are released.
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Exoproteins are proteins that act as toxins
They can either be released directly into the target tissue, into the bloodstream or directly to host cells via pili. |
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