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Title: Histology Review Lectures 1019 110205


1
Histology Review Lectures 10/19 11/02/05
  • The immune and digestive systems

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Myeloid and Lymphoid Immune Systems
Myeloid Granulocytes, monocytes, RBCs,
platelets. Lymphoid Lymphocytes and associated
organs
3
Bone Marrow
  • Blood flows between marrow cords through highly
    fenestrated blood sinuses instead of capillaries.
  • Reticular cells live between the fenestrated
    endothelium and the marrow cells, are important
    for secretion of CSFs (colony stimulating
    factors) and marrow structure (reticular
    fibers-silver stain)

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Hematopoiesis
  • Embryonic
  • 1-3 mo. (gestation) Yolk sac blood islands
  • 3-7 mo. Liver and spleen
  • 7-9 mo. Bone Marrow
  • Child Most bones
  • Adults Most in the pelvis, sternum, ribs.

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Hematopoiesis
  • One type of cell, the pluripotent hematopoietic
    stem cell, lives in the marrow and gives rise to
    all blood cells, including some phagocytes, such
    as Kupffer cells, histiocytes, osteoclasts, etc.
  • Remember! Osteoclasts arise from an early stem
    cell not a granulocyte or monocyte progenitor
    cell.
  • This pluripotent stem cell slowly differentiates
    towards other cell types depending upon the
    stimulating molecules present in the bone marrow
    (GM-CSF, erythropoietin, etc.)

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Erythropoiesis
  • Proerythroblast basophilic (ribosomes), large
    nucleus, undergoes mitosis (m)
  • Basophilic Erythroblast very basophilic
    (ribosomes), smaller, m
  • Polychromatophilic Erythroblast Hb begins, last
    cell that is m
  • Normoblast small, dark nucleus, slightly
    acidophilic due to increased Hb
    (orthochromatophilic)
  • Reticulocyte lost its nucleus, acidophilic-gray
    cytoplasm, many in bone marrow, also found in
    blood of hemorrhaging patients to compensate.
    (Polychromatophilic erythrocyte)

7
RBC
  • 1.     Erythrocyte acidophilic, anuclear,
    biconcave disc, 7-8 microns, 120d life span in
    blood.
  • 1.     Erythropoietin from kidney in response to
    hypoxia causes more mitoses in erythrocyte
    precursors to give rise to more RBCs
  • 2.     RBCs are filled with mostly hemoglobin,
    use glycolysis and pentose phosphate shunt to
    make ATP to fuel enzymatic reactions. No
    mitochondria.
  • Normal RBC count is 4-6 million/microliter blood
    (good for ECM clinicals)
  • Hereditary anemia- sickle cell, thalassemia, etc.
  • Acquired anemia- decreased iron, B12, folate
    intake!!!

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Granulopoiesis (similar for PMN, Eos, Baso)
  • 1.     Myeloblast no granules, basophilic, m
  • 2.     Promyelocyte azurophilic granules appear
    here, indented nucleus, m
  • 3.     Myelocyte Elliptical nucleus, specific
    granules appear here, last m
  • 4.     Metamyelocyte nucleus becomes more
    indented, heterochromatic
  • Band nucleus acquires a U shape, these are seen
    in blood with chronic infections.

9
Lymphopoiesis
  • T-cells- originate in the bone marrow and travel
    to the thymus in the youngster to differentiate.
  • B-cells originate in the bone marrow, MALT,
    spleen.
  • Dont really change appearance as they mature.

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Megakaryocytes
  • 1.     Megakaryoblast last m cell, huge,
    basophilic cytoplasm
  • 2.     Promegakaryocyte really huge, 45 microns
  • 3.     Megakaryocyte enormous, 50-70 microns,
    polyploid, buds off platelets at platelet
    demarcation channels in its peripheral cytoplasm.
    (proplatelet processes)

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The Lymphoid System
  • Primary Lymph Organs
  • Bone Marrow (B cells) and Thymus (T cells)
  • Cells undergo antigen-independent
    proliferation, differentiation. T and B cells
    are weeded out for their ability to recognize
    foreign antigens (without actual antigen present)
  • Secondary Lymph Organs
  • Lymph nodules, Lymph nodes, Tonsils, Spleen
  • Cells undergo antigen-dependent prolif. and
    diff.
  • Contain Lymphocytes (T and B), Macrophages,
    Mesenchymal Reticular Cells (reticular fibers)
  • T and B cells become effector lymphocytes and
    memory cells.

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Diffuse Lymphatic Tissue and Lymphatic Nodules
  • Diff. Lymph. Tissue Accumulations of
    lymphocytes, macrophages strategically placed
    along the gut and respiratory tract. Interaction
    between antigen and cells occurs here, then the B
    and T cells go to the regional lymph nodes to
    differentiate.
  • Lymph . Nodules Localized uncapsulated
    concentrations of lymphocytes. (Appendix, Peyers
    Patches, Tonsils) Reactive lymphatic tissue,
    become enlarged upon encounters with antigen.
    (Also found in lymph nodes). Have a reticular
    stroma.

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Lymph Nodes
  • Small, Encapsulated organs along the pathway of
    lymphatic vessels (filter lymph)
  • Afferent lymph vessels supply it, efferent lymph
    vessels drain it.
  • Supporting structures
  • Capsule - dense connective tissue surrounds the
    node
  • Trabeculae projections of the capsule into the
    cortex
  • Reticular tissue reticular cells and their
    fibers that form a meshwork throughout the node
  • Contain
  • Reticular cells
  • B and T cells
  • Macrophages (reticular macrophages)

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Zones of the Lymph Node
  • Cortex Outer portion of the node
  • Reticular framework, lymphocytes, macrophages,
    plasma cells, lymph sinuses, lymph channels
  • Lymph Nodules (follicles) mostly B cells
    undergoing mitosis from immunoblasts to plasma
    cells and memory cells. Secondary nodules
    contain germinal centers.
  • Deep cortex (paracortex) mostly T cells,
    helping the B cells, activating them, helping
    them recognize antigen.
  • Medulla Inner portion of the node
  • Reticular framework, medullary cords and sinuses.
  • Medullary cords mostly B lymphocytes.

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Lymphocytes enter and exit the node here
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Spleen
  • Morphologic and Immunologic blood filter
  • Encapsulated with trabeculae, Contains Red Pulp
    (Mostly RBCs) and White Pulp (Mostly
    lymphocytes, macrophages)
  • No Cortex or Medulla.
  • White Pulp contains
  • Peri-Arteriolar Lymphatic Sheath (PALS) mostly
    T cells
  • Lymphatic Nodules mostly B cells
  • Lymph nodules, when reactive, can become very
    large (Malphigian Corpuscles)

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Spleen Functions
  • Red Pulp
  • Contains Sinusoids that are highly fenestrated,
    and blood comes in direct contact with
    endothelial-associated macrophages. No
    continuous basal lamina, no pericytes or smooth
    muscle in the sinusoids. RBCs leave the sinuses
    and enter the splenic cords (of Billroth), which
    are made of reticular tissue, macrophages, some
    leukocytes. These macrophages will be filled
    with hemosiderin from the breakdown of senescent
    RBCs.
  • White Pulp
  • Contains lymphatic tissue, mostly involved in
    reactive proliferation of lymphocytes and
    secretion of humoral antibodies.

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Thymus
  • Arises from Endoderm makes a reticular stroma
    no reticular cells, only epithelioreticular
    cells.
  • The lymphocytes in the thymus come from the yolk
    sac and then the bone marrow.
  • T- lymphocytes are selected here many undergo
    apoptosis.
  • Cortex stains dark, Medulla is eosinophilic, less
    densely packed.
  • Contains Hassals Corpuscles, with keratinized
    epithelioreticular cells.

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This is Reticulous!
  • Remember which particular reticular tissue has
    which cell!
  • Epithelioreticular cells Found in thymus
  • Secrete thymosin, form blood/thymus barrier,
    Hassals Corps.
  • NO RETICULAR FIBERS
  • Reticular cells/ fibers
  • Spleen Cords of Billroth (with lymphocytes, et
    al.)
  • Lymph nodes Two kinds of Reticular Cells
    (APCs, fibroblast-like cells)
  • Bone Marrow (adventitial cells support,
    secretes cytokines)
  • Reticulocyte immature RBC (lots of ribosomes)

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The Digestive System
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Lip
  • External part Keratinized. Hair follicles,
    sebaceous glands, thin mucosa.
  • Vermillion Border Blood vessels in the dermis
    come very close to the epithelium, skin appears
    red. Keratinized. No hair follicles or sweat
    glands.
  • Parakeratinized internal part Just internal to
    the vermillion border, some surface cells have
    nuclei, some cells have keratohyalin granules.
  • Mucosa No keratohyalin granules, red connective
    tissue shines through the thick yet transparent
    epithelium.

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External Part
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Vermillion Border
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Tongue
  • Muscle- Skeletal, CN XII, random orientation.
  • Papillae- mucosal elevations on the dorsum of the
    tongue.
  • Filiform most numerous, smallest, keratinized,
    no taste buds.
  • Fungiform on dorsum of tongue, mushroom shaped,
    have taste buds.
  • Circumvallate found near the sulcus terminalis,
    have Von Ebners glands and taste buds in their
    moats
  • Foliate- found on the sides of the tongue, have
    taste buds.

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Circumvallate
Von Ebners Glands
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Taste Buds
  • Oval, pale bodies on papillae
  • Cell types-
  • Neuroepithelial cells have microvilli, connect
    to nerve fibers of CN VII, IX, X.
  • Supporting cells
  • Basal cells- differentiate into the above cells
  • Buds at the tip of the tongue taste sweet
    stimuli, back of the tongue taste bitter.

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Major Salivary Glands
  • Parotid Found deep inside the cheek in front of
    the ear. Totally serous acini. Many adipocytes
    do not confuse these with mucous acini.
  • Submandibular Contains both serous and mucous
    acini, found in the floor of the mouth near the
    mandibular ramus.
  • Sublingual Totally mucous acini, found
    underneath the tongue (surprisingly)

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Salivary Gland Ducts (ISE)
  • Intercalated- low cuboidal, have carbonic
    anhydrase (secrete bicarb), most prominent in
    serous glands.
  • Striated- simple cubo/ columnar, striations in
    the basal membrane- elongated mitos, central
    nuclei. Reabsorb Na and Cl, add K and HCO3.
    Creates Hypotonicity. Intralobular.
  • Excretory- Simple cuboidal to stratified
    columnar, depending on length. Interlobular!


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Saliva and its Ductal modifications
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Changes in electrolytes with changes in flow
rate.
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Saliva
  • Contains
  • a-amylase (1-4 glycosidic bond breaker)
  • Lysozyme (anti-bac), Immunoglobulin A
  • Hi-HCO3, K, Ca. Low Na. (always hypotonic to
    plasma)
  • Sympathetics cause viscous saliva,
    parasympathetics cause watery saliva.

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Striated Duct
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Excretory Duct
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Intercalated Duct
Striated Duct
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GI Tubing in General
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GI Tubing in General
  • Mucosa
  • Epithelium (stratified squamous or simple
    columnar) barrier, absorption, secretion
  • Lamina Propria loose connective tissue,
    contains many blood vessels, lymph vessels,
    immunologic barriers (lymphocytes, eos, mac),
    glands
  • Muscularis Mucosae boundary between muc and
    submuc, inner circular and outer longitudinal
    smooth muscle
  • Submucosa
  • Dense, irregular CT, larger BV, lymphatics, nerve
    plexuses, sensory and motor fibers, Glands in the
    duodenum and esophagus.
  • Muscularis Externa (Propria)
  • Inner circular and outer longitudinal layers of
    SM, Auerbachs nerve plexus
  • Serosa
  • Mesothelium and underlying Conn. Tissue.
    Retroperitoneal structures have adventitial
    surrounding tissue.

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Esophagus
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Esophageal Glands
  • Proper SUBMUCOSA, more concentrated in the upper
    ½ of esophagus. Mucus-secreting, slightly
    acidic.
  • Cardiac Glands LAMINA PROPRIA, found at
    extremities of the esophagus, usually next to the
    stomach. Neutral mucus-secreting (prevents
    against heartburn)

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Esophageal Muscle
  • Upper 1/3 Striated (innervated by somatic motor
    neurons)
  • Middle 1/3 a combination of upper and lower
  • Lower 1/3 Smooth muscle (innervated by vagus
    nerve (CN X)

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Stomach
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Features of the Stomach
  • Mucosa
  • Gastric Pit made up of surface mucous cells,
    stain darker than goblet cells, basal nucleus,
    secretes a thick alkaline mucus, protective.
  • Gastric Gland connects to the gastric pit,
    contains
  • Mucous Neck Cells shorter than surface cells,
    more soluble secretion
  • Parietal Cells Large, clearer cells, secrete HCl
    and Intrinsic Factor in response to gastrin
  • APUD (enteroendocrine cells) do not contact the
    mucosa, secrete gastrin and other hormones
  • Chief Cells secrete pepsinogen, which is
    converted to pepsin, a protease, in the acidic
    lumen of the stomach.

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Parietal Cell Electrolyte Transfer
Gastrin
Acetylcholine
Histamine
  • Gastrin, Ach, Histamine activate this path.
  • Somatostatin inhibits it.

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Features of the Stomach
  • Other Glands
  • Cardiac Glands found in the upper stomach,
    protects esophagus from acid. Connect to the
    gastric pits.
  • Pyloric Glands found in the pyloric antrum and
    the pylorus. Mucus secretion, located in lamina
    propria.
  • Muscularis Externa
  • Innermost oblique, middle circular, outer
    longitudinal muscle layers.
  • Rugae folds of mucosa and submucosa

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Small Intestine (Duodenum, Jejunum, Ileum)
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Small Intestine Characteristics
  • Mucosa Contains microvilli, villi (folding of
    the mucosa), and plicae circularis (folding of
    the submucosa). Three ways to increase surface
    area.
  • Cells of mucosa
  • Enterocytes (brush border, simple columnar.)
  • Goblet cells (few microvilli, huge mucus cup)
  • Paneth Cells (secrete lysozyme, found at bottom
    of intestinal crypts of Lieberkuhn)
  • APUD cells

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Duodenum
  • Submucosal glands (of Brunner)
  • Secrete HCO3, glycoproteins
  • Regulates the pH so that pancreatic enzymes work!

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Paneth Cells in Jejunum
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Paneth vs. APUD cell
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Trends in the Intestine
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Colon



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Differences Between Colon and the rest of the GI
Tract
  • The colon has a strong collagen table, a
    thickening of collagen fibers just below the
    epithelium
  • There are no villi, just crypts. No Paneth Cells
    normally.
  • The outer longitudinal layer of SM forms strong
    bands (Taenia Coli) and is very sparse between
    them, except in the rectum, where the outer layer
    is confluent.
  • There are no lacteals in the colon.
  • A pericryptal fibroblast sheath in the lamina
    propria secretes reticular fibers that line the
    epithelium.

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Vermiform Appendix
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Liver
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Liver Function
  • Detoxification of Blood
  • Kupffer cells (phagocytosis), Enzymatic
    degradation of drugs and toxins, Excretion of
    metabolites into bile or urine.
  • Carbohydrate and fat metabolism
  • Gluconeogenesis, Glycogenolysis, Release of
    glucose into blood, et al.
  • Triglyceride, Cholesterol, Ketone synthesis
  • Albumin, Plasma protein synthesis
  • Bile Synthesis, conjugation of bilirubin.

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Liver Acinus vs. Lobule
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Liver Cells
  • Hepatocytes
  • Have junctional complexes, gap junctions
  • Carry out all functions in the liver (metabolism,
    bile synthesis)
  • Have sER and rER, Microvilli, Bile canaliculi
  • Kupffer Cell
  • Liver macrophage, derives from monocyte
  • Lives in the Space of Disse and in the Blood
    Space, clears pathogens, lipoproteins, immune
    complexes
  • Stellate (Ito) Cell
  • Produces collagenase, metalloproteinase
    inhibitors, become activated during cirrhosis.
  • Endothelial Cell
  • Highly Fenestrated, takes up blood components and
    delivers them to the Space of Disse

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The Space of Disse
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Gall Bladder
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Gall Bladder Features
  • Stores and concentrates bile from the liver
  • GB cells actively transport Na out of its
    basolateral membrane, and water from bile follows
    osmotically.
  • Simple Columnar Epithelium
  • Microvilli, junctional complexes, lateral
    plications
  • No muscularis mucosae or submucosa.
  • Rokitansky-Aschoff Sinuses invaginations of the
    epithelium where bacteria can grow

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Pancreas
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Exocrine Pancreas
  • The pancreas secretes
  • Trypsinogen, Chymotrypsinogen, Proelastase,
    Procarboxypeptdase, Prophospholipase, Procolipase
    these are zymogens.
  • Trypsinogen is cleaved by intestinal enterokinase
    to trypsin, and trypsin activates the rest.
  • Also, lipase, amylase, cholesterolesterase,
    RNAse, DNAse
  • These secretions mix with a bicarbonate-rich
    fluid and enter the pancreatic duct and head for
    the duodenum through the sphincter of Oddi.
  • CCK stimulates the release of enzymes, Secretin
    stimulates the intercalated duct system to
    release more bicarb-rich fluid. Pancreatic
    Polypeptide inhibits CCK at the acinar cell

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Endocrine Pancreas
  • The Islets of Langerhans are interspersed between
    acini and are highly vascularized.
  • Alpha cells- peripheral in the Islet, secrete
    glucagon. (Raises blood sugar)
  • Beta cells- central in the Islet, secrete insulin
    (Lowers blood sugar, increases protein and fat
    synthesis, glycogenesis)
  • Delta cells- secrete somatostatin (inhibits both
    glucagon and insulin, as well as gastrin,
    secretin, CCK)
  • D1 cells- secrete VIP (like glucagon, but also
    affects the GI tract tone and secretion
  • F cells- secrete PP (inhibits bile secretion,
    stimulates gastric enzyme secretion
  • EC cells- secrete motilin, serotonin, subst. P
    (vasodilation, increased gastric emptying)

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Insulin
  • A polypeptide hormone, derived by cleavage from
    proinsulin to insulin and C-peptide.
  • GLUT-2 Receptors in the beta cells take up
    glucose, which signals the beta cell to
    manufacture and secrete insulin. Amino acids and
    GI hormones also can activate beta cells.
  • Insulin is secreted into the bloodstream, where
    it comes in contact with skeletal muscle or fat
    cells. The insulin causes the GLUT-4 receptor to
    localize to the membrane, increasing the amount
    of glucose that can enter the cell.
  • The insulin receptor is a tyrosine kinase that
    autophosphorylates upon contact with insulin.

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The cellular response to insulin
  • GLUT-4 activation

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Panc. Duct
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Islet
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Paul Langerhans
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Acinar Cells
  • ZG- zymogen granule
  • Asterisk- lumen

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