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Gastrointestinal Physiology 2 :poop: (Secretion (Types of GI Secretions…

- - - - Prevent bacterial colonisations
      - activate some specific enzymes that initiate protein digestion (e.g. pepsinogen)
      - Brief review on pH and acid/base reactions
        
        Secretions that contain H+ will decrease pH (more acidic)
        
        Secretions that increase HCO3- will increase pH (less acidic)
  - - - 4 main functions
        
        Cleanse the mouth
        
        Initiation of food breakdown (chemicals) so they can be tasted
        
        Moistens and compact food into a bolus
        
        Starts enzymatic breakdown of food
      - Secreted by specialised secretory glands
        
        Submandibular (below the mandible)
        
        Parotid (near the ear)
        
        Sublingual (below the tongue)
        
        :one: Secretion involves highly specialised
        cells that produce what is needed
        
        made up of functional units described as tubuloalveolar structures
        
        Acinar cells
        
        Serous cells
        
        secrete water + enzymes
        
        Mucous cells
        
        secrete mucous
        
        :two: Secretion is a 2-stage process
        
        Primary secretion
        
        Amylase-containing, water + Na+, K+, Cl-, HCO3- same as in plasma
        Occurs in the acinar part
        
        Secondary secretion
        
        Na+ is reabsorbed, HCO3- is released
        Occurs in the ducts
      - Final saliva is hypotonic (means lower osmolarity than plasma) and slightly alkaline because of HCO3-.
        Presence of HCO3- thought to be a protection system against possible refluxes of acidic gastric juices.
        Total saliva output: 1-1.5 liters/day
        
        Mucins
        
        constituents of mucous
        
        Lysozyme
        
        inhibits bacterial growth
        
        Salivary amylase
        
        enzyme that starts chemical digestion of carbohydrates
        
        Metabolic wastes (urea)
        
        Water (~97-99%)
        
        Electrolytes
      - Control of salivary secretion is EXCLUSIVELY neural
  - - - Secretion by epithelial cells
      - Secretion by gastric glands
    - - 4 different cell types
        
        Surface epithelial cells
        
        HCO3-
        
        Buffer acidity near gastric wall
        gastric mucosal protection system
        
        Mucous neck cells
        
        Mucus
        ~0.2mm
        
        Protect gastric wall
        
        Parietal cells
        
        H+
        
        Lower pH
        
        HCl --> H+ + Cl-
        
        Production of H+ starts when CO2 from the bloodstream combines with water to create carbonic acid (H2CO3) with an activator (carbonic anhydrase).
        
        H2CO3 splits to form H+ and HCO3-.
        
        H+ pumped into the lumen by hydrogen-potassium exchanger/"proton pump", which pumps out H+ and in K+ by using energy from ATP
        
        HCO3- goes back into the bloodstream by another membrane exchanger which brings in Cl-
        
        Results: H+ + Cl-
        
        Intrinsic factor*
        
        Absorb vitamin B12
        
        Features
        
        Vast network of canaliculi
        
        upon cell activation, fuse with the membrane to allow the content (HCl) to go into the lumen
        
        Abundance of mitochondria
        
        power plant of the cell and produce the ATP, which is necessary to make the proton pumps function
        
        Chief cells
        
        Pepsinogen
        
        converted to Pepsin at low pH
        
        Lipase*
        not related to acid balance
        
        Digestion of lipids
  - - - Liver
        
        Receives 'first-hand' blood from small intestine (gate-keeper). Metabolizes/De-toxifies everything that gets absorbed into the bloodstream
        
        Contributes to fatty acids metabolism
        
        Contributes to digestion by secreting bile
        
        Liver produces bile continuously
        
        Bile is stored and concentrated in the gallbladder (water is absorbed)
        
        Bile
        
        Enzymes
        
        Salts
        
        When the acidic food from stomach reaches the small intestine (duodenum), the cells in duodenal epithelium release a hormone, called cholecystokinin (CCK).
        
        This triggers the Oddi sphincter to open, and at the same time, contraction of the muscles around the gallbladder so that the bile stored is released into the small intestine. Production of pancreatic juice is also stimulated
      - Pancreas
        
        Pancreatic juice
        
        similar to saliva
        
        secreted by acinar cells
        
        cells lining the pancreatic duct secrete HCO3-
        
        makes the solution alkaline to neutralise the acid chyme in the duodenum from the stomach
        
        Water
        
        Enzymes (inactive form)
        to prevent self-digestion of the pancreas
        
        With names:
        pro-X
        X-ogen
        
        Secretes pancreatic juice
        
        Produces insulin that is generated by islets of Langherans
- - - - Principle of protein digestion: enzymatic reduction to amino acids (or short peptides)
        
        Amino acids that are not synthesised by human body:
        
        Lys
        
        Val
        
        Leu
        
        Ile
        
        Phe
        
        Tyr
        
        Thr
        
        Met
        
        Amino acids that are synthesised by human body:
        
        Glu
        
        Gln
        
        Asp
        
        Asn
        
        Pro
        
        Hydroxypro
        
        HOW are proteins digested
        
        Proteins
        -- (Pepsin and H+ in gastric lumen) -->
        Large peptide chains
        -- (Pancreatic juice in intestinal lumen) -->
        Oligo-peptides
        -- (Oligo-peptidase at brush border) -->
        single amino acids or di-/tri-peptides
        
        General idea: luminal surface is not smooth
        Protruding structures called microvilli are observed. The objective is to increase available surface area for absorption, but also for digestion
        CONCEPT OF BRUSH BORDER
    - - 3 classes of lipids
        
        Cholesterol (dietary and in bile)
        found in food and bile
        
        Phospholipids
        used to make cell membranes
        
        Triglycerides
        found in vegetable oils and animal fats
        
        3 long fatty acid chains held together
        by glycerol backbone via 3 ester links
        
        lipases break the ester links
      - Lipid digestion
        
        First phase: Stomach
        
        Gastric lipase secreted by chief cells is only able to break 2/3 ester links
        
        Second phase: Small intestine
        
        Pancreatic lipase is able to break all 3 ester links
        
        Pancreatic juice also contains cholesterol esterase for cholesterol breakdown and phospholipase A2 for phospholipids breakdown
        
        Problem: Immiscible lipds and water form separate layers, small surface area for digestion by enzymes
        
        Solution: Emulsification
        break down fat layer into small droplets to be dispersed throughout the watery layer and "attacked" by the lipase enzymes
        
        :key: Key player
        
        Bile contains bile salts that will coat fat droplets and prevent them from re-aggregating into a big fatty layer
        Process facilitated by intestinal motility that help mix bile salts and fat gobules
      - Lipid absorption
        
        Products of lipid digestion (fatty acids and monoglycerides) -->
        easy entry into enterocyte (lipophilic)/cell by diffusion -->
        Re-esterification in endoplasmic reticulum -->
        "New" lipids + specialised proteins = chylomicron -->
        chylomicron taken up by the lymphatic system
        
        Chylomicron serves as a carrier for lipids around the body
    - - Principle of carbohydrates absorption: co-transport with Na+ ions for glucose and galactose
        facilitated diffusion by GLUT5 transporter for fructose
        
        transported inside the cell
        
        Fructose is taken up by a specific membrane transporter belonging to the GLUT family
        
        Na+/glucose transporters (SGLTI) co-transports glucose and Na+
        Note: the Na+ that came into the cell is eliminated by the energy-consuming Na+-K+ pump
        
        on the side facing the interstitial space near the blood vessel
        
        glucose and fructose are actively transported into the bloodstream by similar active processes
      - Principle of carbohydrates digestion: enzymatic reduction to monosaccharides
        e.g. glucose and fructose
      - 3 categories
        
        Starch (a mixture of straight (amylose) and branch (amylopectin) chain molecules)
        
        Vegetable fibers
        not digested by any enzyme in human body but by a flora of exogenous bacteria
        digestion happens in the colon
        
        Disaccharides (Sucrose and Lactose)
- - - - Secretion of enzymes through a duct into a surface covered by epithelium (e.g. pancreas secretes pancreatic juice into the duodenum)
    - - Secretion of hormones with effects only in the vicinity (e.g. a cell secretes a hormone to signal a neighbouring cell)
    - - Secretion of hormones directly into bloodstream (e.g. pancreas secrete insulin and glucagon)
  - - - Glucose released by liver cells to raise blood glucose level to normal
  - - - Blood glucose level falls
  - - - Pancreas does not produce insulin
    - - A. Insulin resistance
        B. Impaired insulin production
        C. Increased rate of glucose production
    - - Long term consequences:
        
        Retinopathy
        
        Neuropathy
        
        Cardiovascular disease
        
        Gastroparesis
        
        Kidney disease