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Gastric Juice, Connective Tissue, Proteoglycan Roles - Coggle Diagram

- - - - Top of stommach
      - Sticks out above cardiac sphincter
    - - Body of stomach
    - - Outside exterior surface
    - - Inside exterior surface
    - - Bottom of stomach
      - Where most churning occurs
    - - Exit of stomach
    - - Start of small intestines
  - - - Outside stomach
      - Composed of connective tissue
    - - Mesenteric autonomic nerve plexus
      - Circular muscle
      - Longitudinal muscle
      - Submucosal autonomic nerve plexus
    - - Arterioles plexus
    - - Gastric glands
        
        Endocrine cells
        
        Chief peptic cells
        
        Parietal cells
        
        Mucus neck cells
      - Lamina propria
        
        Connective tissue
        
        Lymph nodes
      - Muscularis mucosa
        
        Smooth muscle
      - Epithelium
        
        Surface mucus cells
    - - Unlike rest of digestive system
      - Goblet cell presence implies disease (ie metaplasia, cancer)
  - - - Lower layer
        
        150 um thick
        
        Shear + pH resistant
      - Upper layer
        
        Variable thickness
        
        Converts into viscous liquid to assist stomach content movement
    - - Degrades mucus
      - Degradation balanced by secretion
    - - Prevents neutralisation
      - Only epithelial surface pH neutralises
    - - Genes
        
        MUC5AC/MUC6 in stomach
        
        MUC2 in small intestines
      - Structure
        
        Globular N-terminal
        
        Globular C terminal
        
        Densely-glycosylated regions between
        
        Require OH groups from STP regions
        
        Threonine
        
        Proline
        
        Serine
        
        Joined by disulphide bridges
        
        Polymerises at both ends to form long linear molecules
      - Function
        
        Cleaved by pepsin between glycosylated regions
        
        Solubilises gel
        
        Gives highly glycosylated regions resistant to proteolysis
        
        Metabolised by colonic bacteria
        
        Forms gel via polymerisation
- - - - 35%of parietal cells therefore filled with mitochondria
    - - Increases circulating gastrin
      - Once pump becomes functional, causes huge acid rebound
      - Increases pH of reflux, doesn't stop it
      - PPI binds to cysteine SH groups
- - - - Zymogen activated by low pH
      - Also secrete intrinsic factor
      - Secrete pepsin zymogen
    - - Base of gland
      - Several types
        
        Enterochromaffin-like cells
        
        Histamine-secreting
        
        Increase acid secretion
        
        Acts with gastrin
        
        D-cells
        
        Somatostatin-secreting
        
        Inhibit acid secretion
        
        Stimulates gastric emptying
        
        Enterochromaffin cells
        
        Serotonin-secreting
        
        Involved in GI homeostasis
    - - Gastrin-secreting
  - - - A
        
        Located on 11q13
        
        Pepsins 1/2/3a,b,c/4
        
        Pepsin 3 a,b,c main pepsins in human gastric juice
      - C
        
        Gastricin
        
        Located on chromosome 6
        
        Gives pepsins 5,6
    - - Autocatalytic
        
        At pH >5, His, Lys, Arg +ve, Asp, Glu -ve
        
        Form salt bridge
        
        Asp, Glu become neutral at pH <5.0
        
        Salt bridge doesn't form
        
        Substrate falls into active site
        
        Cleaved at AA 16/17
        
        Hydrophobic region
        
        Leucine/Isoleucine
        
        Forms propepsin
        
        Cleaves other propepsin molecules at AA 44/45
        
        2 more items...
      - Activated at pH <5
- - - - 2) Fibrillation
        
        3) Erosion of cartilage + exposure of subchondral bone
  - - - Inflammatory cells
      - Chondrocytes
    - - Degradation fragments diffuse out of tissue
      - Porosity of matrix increases
      - Degradative enzymes penetrate further
      - PGs leech out, collagen loses stiffness causing cartilage lesions
  - - - Much larger than enzymes
      - Difference in diffusion rates
  - - - Higher CS/KS ratio + richer in C4S than C6S
      - Immature PGs
        
        Less associated with matrix + more easily degraded
        
        Failure to repair
        
        Apoptosis + lacunae in tissue
  - - - Contains growth factors + cytokines to reduce inflammation + tissue damage
      - Prepared by double centrifugation of blood to pellet platelets which are injected into joints
      - Much better at reducing pain than steroids
      - Better than hyaluronic acid or placebo, benefit increasing over time
      - Filardo et Al (2021)
    - - Every 3 weeks
      - OA reduces size and conc of HA in synovial fluid
      - High MW as good or better than NSAIDs
      - No better than corticosteroids
      - Webner et Al (2021)
- - - - Ground substance
      - Fibres
        
        Types
        
        Collagen
        
        Elastin
        
        Parallel of crisscross meshwork
        
        Proportion of fibrillar proteins + other constituents determine tissue characteristics
- - - - Annulus fibrosus
      - Repair
    - - Elastin
      - Ear lobes
      - Epiglottis
    - - Articulating surfaces
      - Distal end of ribs
      - Cartilage plates in nasal septum, larynx, trachea, bronchi
      - Firm and flexible
        
        Flexibility from proteoglycan content
        
        Highly -ve charge
        
        Occupy 30-50x own dry weight in normal joint
        
        Large volumes of water retention
        
        Immobilised as aggregates in collagen matrix
        
        Restrained from swelling
        
        Gives cartilage firm + flexible properties
        
        Collagen removal would result in PGS expansion + gel formation
        
        Reversibly compressible via displacement of water from hydration shells
        
        When load is applied, fluid is displaced from PG domains at point of load application
        
        Fluid redistributed within tissue
        
        Slow due to PG in meshwork impeding fluid flow
        
        Sliding of bottlebrush structure causes frictional drag
        
        2 more items...
        
        Addition of LaCl3 causes PG precipitation + loss of reversible compressibility
        
        Rigidity from collagen content
        
        30% glycine. 30% proline/hydroxyproline
        
        Also contains hydroxylysine
        
        Made of aggregated tropocollagen molecules
        
        Type 2 trans helix
        
        Gly-x-x-gly-x-x-gly
        
        Insoluble
        
        Types
        
        Anchoring fibrils
        
        VII
        
        Networks
        
        VIII
        
        X
        
        IV
        
        Beaded filaments
        
        VI
        
        Anchoring basement membranes to stroma
        
        XV
        
        XVIII
        
        Fibril-forming collagens
        
        XI
        
        XXIV
        
        V
        
        III
        
        II
        
        Form heterofibril with collagen IX in articular cartilage
        
        1 more item...
        
        XXVII
        
        I
        
        Trans-membrane domain-containing
        
        XVII
        
        XXV
        
        XIII
        
        29 types
        
        Stabilised by covalent cross-links
        
        Dysfunction
        
        Ehlers-Danlos
        
        SCAD
- - - - Glycosoaminoglycan polysaccharide chains
        
        Joined by reducing terminal sugar residues to protein
        
        Bottle-brush conformation
        
        Highly negatively charged
        
        OSO3-
        
        COO-
        
        Types
        
        Galactose-derived keratan sulphate
        
        Glucuronic acid-derived chondroitin-6-sulphate
      - Low protein, high CHO
  - - - Interacts with Hyaluronan (GAG)
        
        Non-sulphated
      - Evidence for key residues
        
        Reducing disulphide bridge 5-7 abolishes aggregation
        
        Intact arginine + tryptophan residues required to provide hydrophobicity to maintain globular formation
        
        Substituting free e-amino group on lysine for bulky group abolishes charge-charge NH3+ interactions
        
        G1 region specific for HA repeating unit
        
        Does not bind to other polyelectrolytes when glucosamine replaced by galactosamine
        
        Intermediate of heparin biosynthesis almost identical to HA with alpha instead of beta groups doesn't interact
        
        4 carboxyl groups + 3 or more N-acetyl groups necessary for interaction
    - - CS2
      - CS1
    - - 100 CS chains
        
        Large, 20,000MW
        
        40 repeating disaccharides, 80 -ve charges
      - 30-60 KS chains
        
        Small, 4-8000 MW
        
        8-16 repeating disaccharides, 8-16 -ve charges
      - C2 clustered
      - C1 evenly distributed
- - - - Major soluble CS-PG in brain
      - Can be removed by PBS
  - - - Aggrecans in brain
      - Any PG with G1 + G3/lectin domain
      - Major PG:
        
        Aggrecan
        
        Neurocan
        
        Versican
        
        Interacts strongly with Tenascin R
        
        Brain matrix protein
        
        Exists as monomer, dimer, trimer
        
        Interacts in glial tissue as part of white matter
        
        Acts as buffer against pressure change
        
        Only glial cells move in matrix therefore cancers cannot metastasize into the brain
        
        Brevican
- - - - Midguts salivary glands + ovaries dissected from mosquitoes
      - GAGs extracted and precipitated
      - GAGs digested w/ Chondroitinase ABC then undergoes HPLC analysis
      - GAGs digested with hyperain lyase and prepared for surface plasmon resonance
    - - SPR
        
        1:1 binding with HS + CSP
        
        Binding has slow association/dissociation
      - Conclusions
        
        Plasmodium sporozoites use HS PGs to localise target organs
        
        Syndecan abundant in mosquito salivary glands
        
        Mosquito midgut has lower levels of chondroitin sulphate
        
        Binding may need both GAGs and CSP
  - - - Travel to liver, invading hepatocytes via HS PG binding
        
        Sporozoites become exoerythrocytic, multiply + burst from liver cells as merozoites
        
        Enter erythrocytes
        
        Mature
        
        Divide
        
        Some differentiate to gametocytes
        
        Mosquito bites infected humans, gametocytes enter mosquito gut
        
        Fertilisation occurs, producing a zygote
        
        Zygote differentiates into an ookinete
        
        1 more item...
  - - - Competes with CSP for binding site
  - - - Soluble basigin inhibits invasion
      - More expressed in Ok blood group
- - - - Sporozoite surface protein contains basic clustered amino acids (ie lysine + arginine)
      - +ve charge interacts with -ve HS GAG chains
  - - - Site directed mutagenesis of AA 222-226
      - Invasion assay involving migration through collagen gel
      - Controls
        
        Mutated syndecans expressed at surface have same HS chains as WT
        
        Western blotting shows wild type + del identical in size
        
        Immunohistochemical antibody staining shows syndecan still expressed
        
        Secondary structure analyses shows structure of core protein unaltered
      - Conclusions
        
        Syndecan-1 has anti-invasion properties
        
        Important region near cell membrane 222-226 aa
        
        222-226 mutation does not affect other syndecan properties
- - - - Microciona Prolifera
      - Halichondria Panicea
      - Cliona Celata
    - - Removal of PGS abolishes self-recognition
      - Hybrids form upon abolition of self-recognition
  - - - Other systems use MHCs (MLAs in humans)