OS 206: Abdomen and Pelvis - Common GI Tests PDF

OS 206: ABDOMEN AND PELVIS GI SECRETION AND BILIARY SECRETION / COMMON GI TESTS UPCM 2029 | Dr. Carlos R. G. Cuaño | LU3 A.Y. 2024-2025 ○​ Parasympathetic: Increase...

OS 206: ABDOMEN AND PELVIS GI SECRETION AND BILIARY SECRETION / COMMON GI TESTS UPCM 2029 | Dr. Carlos R. G. Cuaño | LU3 A.Y. 2024-2025 ○​ Parasympathetic: Increase OUTLINE ○​ Sympathetic: Increase/Decrease I.​ Overview of GI Secretion IX.​ Liver Disease ​ Hormonal stimulation A.​ Gastrointestinal Tract Classifications And B.​ GASTROINTESTINAL TRACT SECRETIONS (GIT) Glands Markers ​ The pH of the secretions is fine-tuned to the optimal pH where the B.​ Gastrointestinal Tract A.​ Hepatocellular secretion is released Secretions B.​ Cholestatic II.​ Salivary Secretion C.​ Mixed ○​ e.g. gastric secretions require an acidic environment for A.​ General Information D.​ Infiltrative pepsinogen to be cleaved into pepsin B.​ The Salivon X.​ Markers of Liver Table 1. VOLUME AND PH OF GIT SECRETIONS C.​ Salivary Glands Function & Protein TYPE OF SECRETION DAILY VOLUME (mL) pH D.​ Salivary Secretion Synthesis III.​ Esophageal Secretion A.​ Serum Albumin Saliva 1000 6.0-7.0 IV.​ Gastric Secretion B.​ Prothrombin Times Gastric Secretion 1500 1.0-3.5 A.​ General Information C.​ Serum Bilirubin B.​ Secretions of the XI.​ Clinical Correlates Pancreatic Secretion 1000 8.0-8.3 Stomach A.​ Determining What is Bile 1000 7.8 C.​ Gastric Parietal Cells Predominant Small Intestine Secretion 1800 7.5-8.0 D.​ Phases of Gastric B.​ R-Value Secretion C.​ Summary of Liver Brunner’s Gland Secretion 200 8.0-8.9 E.​ Gastric Acid Negative Function Tests Large Intestinal Secretion 200 7.5-8.0 Feedback D.​ Nonhepatic Sources F.​ Mucous Neck Cells for Lab Tests Total 6700 G.​ Gastric Secretion E.​ Labs for Acute ​ Glands associated with the GIT release water and substances into Summary Pancreatitis the gastrointestinal tract lumen V.​ Pancreatic Secretion F.​ Tumor Markers ○​ Must be coordinated with motility; otherwise, mixing and A.​ Pancreatic Duct XII.​ Imaging digestion will not happen Morphology A.​ Abdominal B.​ Pancreatic Secretions Ultrasound II.​ SALIVARY SECRETION VI.​ Intestinal Secretion B.​ CT Scan & MRI A.​ Small Intestine C.​ Endoscopic A.​ GENERAL INFORMATION Secretion Procedures ​ Salivary secretions are the first secretions in the GIT B.​ Large Intestine D.​ Esophageal pH & ​ 3 pairs of major salivary glands Secretion Manometry ○​ Produce 1,000-1,500 cc of saliva per day VII.​ Biliary Secretion XIII.​ Sample Cases ○​ Parotid gland A.​ Liver XIV.​ References ○​ Submandibular gland B.​ Gallbladder ○​ Sublingual gland VIII.​ Liver Tests ​ Minor salivary gland: Buccal glands I.​ OVERVIEW OF GI SECRETION ​ Role of the Gastrointestinal (GI) System ○​ Mechanically and chemically break down food into absorbable components ○​ Absorption depends on the sequential exposure of mechanically digested food to different secretions A.​ GASTROINTESTINAL TRACT (GIT) GLANDS SECRETION FROM SECRETORY GLANDS ​ Enzymes ○​ Digestion ​ Mucous secretions ○​ Lubrication and protection Figure 2. Salivary Glands SECRETIONS OF THE SALIVARY GLAND ​ Organic ○​ Digestive enzymes: Amylase, Lingual Lipase ○​ Mucin, IgA, Lysozyme, Lactoferrin ​ Inorganic: Electrolytes ○​ Salivary flow will affect salivary secretion ​ Low rates: ​High K+ ​Low Na+, Cl-, HCO3- ​ High rates: ​Low K+ ​High Na+, Cl-, HCO3- Figure 1. Gland Secretion in the GIT ​ Functions TYPES OF GI GLANDS ○​ Initiate digestion ​ Carbohydrate digestion is initiated in the mouth by amylase; ​ Single Cell Mucous Glands fat digestion by lingual lipase ○​ Simplest ○​ Lubricate bolus ○​ e.g. Goblet cells, Mucous cells ​ Mucins, glycoproteins ​ Pits ​Organic secretions ○​ e.g. Crypts of Lieberkuhn ○​ Buffering ​ Deep tubular glands ​ HCO3-, ○​ e.g. Gastric Oxyntic Glands ​ Amphoteric protein ​ Complex glands ​ Basic pH (pH7) is needed in the mouth for enzymes to work ○​ e.g. Salivary glands, Pancreas, Liver ○​ Solvent for taste buds BASIC STIMULATION OF GIT GLANDS ○​ Speech ​ Local Epithelial ○​ Antibacterial ​ Enteric Nervous System (ENS) ​ Immunoglobulin A (IgA): Surface antibody against viruses and ○​ Tactile bacteria ○​ Chemical ​ Lysozyme: Breaks down bacterial cell wall ○​ Distension ​ Lactoferrin: Chelates iron ​ Autonomic Nervous System (ANS) ○​ Tooth integrity Trans 03 TG02: Alfaro, Alog, Ambil, Amigable, Andonaque, Ang, Aningga TH: Kiunisala 1 of 15  ○​ Farther from the initial composition of the primary secretion Note: This section was directly lifted from 2028 Trans. ○​ High K+ B.​ THE SALIVON ○​ Low Na+, Cl-, HCO3- Figure 3. Salivon Figure 6. Electrolyte Concentration vs. Salivary Flow ​ Salivon: Functional unit of the salivary duct system ○​ Acinar cells: Release primary secretion REGULATION OF SALIVARY SECRETION ○​ Ductal cells: Modify secretions ​ Almost exclusively nervous ○​ Myoepithelial cells ​ Sympathetic (i.e. high stress) ○​ Scanty, thick, viscid C.​ SALIVARY GLANDS ​ Parasympathetic ○​ Large volume, watery, decreased enzymes ​ Parotid ​ Unconditioned and conditioned reflex ○​ Serous or watery ○​ e.g. Pavlov’s dog experiment ​ Submandibular ○​ Mixed ​ Sublingual ○​ Mucous Figure 7. Regulation of Salivary Secretion by the Parasympathetic Nervous System Table 2. STIMULI FOR SALIVARY SECRETION Figure 4. Salivary Gland and Its Secretory Cells D.​ SALIVARY SECRETION INCREASED DECREASED PRIMARY AND SECONDARY SECRETION ​ Chewing ​ Sleep ​ Thinking of food ​ Dehydration ​ Isotonic → Hypotonic ​ Primary secretion ​ Ingestion of sour/spicy food ​ Fear, anxiety ○​ Secreted by Acinar cells ​ Mumps ​ Secrete a nearly isotonic salivary solution similar to plasma ○​ Infects salivary glands ○​ Amylase mucous ECF ○​ Eating sour food will stimulate salivary glands and cause pain ​ Tubular modification → Secondary (2°) secretion ​ Sense of taste will be decreased by fear or anxiety through a ○​ Duct cells modify the isotonic solution decrease in saliva ​ Na+ active absorption (removal) ​ Cl- passive absorption (removal) III.​ ESOPHAGEAL SECRETION ​ K+ active absorption (addition) ​ Glands: mainly mucous cells ​ HCO3- secretion (addition) ​ Secretion: Mucus ​ For buffering towards pH7 ​ Control: Local Reflexes ​ End product: hypotonic, alkaline secretion ​ Esophagus ○​ Alkaline secretion is needed to inhibit bacterial growth and ○​ Transit tube between mouth and stomach neutralize the reflux of gastric acid ​ To lubricate the bolus as it passes through the esophagus IV.​ GASTRIC SECRETION A.​ GENERAL INFORMATION ​ 1.5 Liters a day ​ pH: fasting 1.0 – 2.0 ​ Acid secretion ○​ Initiates protein breakdown ○​ Optimal pH for pepsin ○​ Antibacterial properties ​ Intrinsic Factor ○​ Used for DNA synthesis ○​ Vitamin B12 absorption in the terminal ileum of the small intestines ​ Vit. B12 deficiency causes pernicious anemia ○​ Most indispensable secretion of the stomach Figure 5. Primary Secretion in Salivary Glands ​ You can survive without a stomach, but you cannot survive ​ Fast rate of secretion without the intrinsic factor ○​ Ductal cells will not have enough time to modify the primary ​ If without stomach: must be supplemented with parenteral secretion vitamin B12 administration ○​ Closer to the composition of primary secretion ​ Mucus ​ Low K+ ○​ Lubrication protection ​ High Na+, Cl-, HCO3- ​ Pepsinogen ○​ HCO3- remains high ○​ Precursor of pepsin ​ The secretion from duct cells and acinar cells is stimulated ○​ Produced in proenzyme form even if the flow is faster ​ Pepsin is the main protein-digesting secretion of the stomach, ​ Slow rate of secretion but it cannot digest proteins completely OS 206 GI Secretion and Biliary Secretion / Common GI Tests 2 of 15  B.​ SECRETIONS OF THE STOMACH ​ Stimulates all key players in the stomach ​ All the cells are stimulated by acetylcholine (ACh) ​ Different parts of the stomach have different secretions ○​ EXCEPT gastrin-releasing cells (G Cells) that are stimulated by ○​ Cardia and Pylorus gastrin-releasing peptide (GRP) ​ Mucus-secreting glands (mucus neck cells) ○​ Body GASTRIC SECRETION PROTON PUMP ​ Mucus ​ Pepsinogen ​ HCl → maintains acidic environment for the digestion of foodstuff ○​ Antrum ​ Mucus ​ Pepsinogen ​ Gastrin → released as an endocrine hormone Figure 11. Gastric secretion proton pump ​ This is the mechanism of H+ and Cl- secretion by an activated parietal cell in the gastric mucosa ○​ Takes place in the parietal cells of the stomach ○​ Carbonic anhydrase ​ H2CO3 → H+ + HCO3– ​ Source of hydrogen protons for the proton pumps Figure 8. Gastric Regions Showing Different Secretions ○​ Proton Pump or H+-K+ ATPase pump (luminal side of the gastric FUNDIC GASTRIC GLANDS cell membrane) ​ H+ ions are secreted across the luminal membrane ​ Primary active transport ​ Inhibited by proton pump inhibitor drugs ​Such as omeprazole ○​ Cl–/HCO3– exchanger (basolateral side of the membrane) ​ Transports bicarbonate in exchange for chloride ions ​ Maintains intracellular pH ​To counter the basic environment caused by the proton pump ​ Alkaline Tide ​Temporary increase in blood pH after a meal ​Release of bicarbonate (HCO3–) in the bloodstream ○​ Results in a relative loss of protons (H+) ​Aims to maintain intracellular pH to counteract the increase in pH brought about by the secretion of H+ by the proton pump (H+-K+ pump) Figure 9. Gastric Pit Showing The Secretory Cells Of The Stomach ​ Fundic or Oxyntic Gland (Fundus and Body) ○​ Parietal Cells ​ Acid ​Sterilize ​Begin hydrolysis of proteins ​ Intrinsic factors for Vitamin B12 production ○​ Chief Cells ​ Pepsinogen ​Turns into protein for protein digestion ​Mnemonic: PepsiChief ​ Gastric lipase Figure 12. Effect of the Gastric Secretion Rate on the Composition of the Gastric Juice ​Fat digestion ​ NOT sufficient to fully digest triglycerides C.​ GASTRIC PARIETAL CELLS ○​ Enterochromaffin Cells ​ Contains the proton pumps ​ Histamine ​ Very specialized with different components: ○​ Surface Mucous Cells ○​ Intracellular canaliculi (C) ​ Mucus, bicarbonate ○​ Tubulovesicular structures (TV) ​Protects stomach from digesting itself ​ Store H+-K+ ATPase pump or proton pumps when at rest ​ Trefoil peptide ​ When active, these vesicular structures fuse with the ​Stabilize mucus bicarbonate layer canaliculi (which are invaginations of the apical membrane) → ​ Important for protecting the lining of the stomach to ensure that the proton pumps are in position MECHANISM OF GASTRIC SECRETION ○​ Mitochondrion (M) ​ Many mitochondria to power proton pumps → H+ out of parietal cell against concentration gradient ○​ Golgi Apparatus (G) ​ For packaging of protein production Figure 10. Vagal Activation Stimulates Multiple Cell Responses via Neurotransmitters Figure 13. Resting (A) and Active (B) Parietal Cells OS 206 GI Secretion and Biliary Secretion / Common GI Tests 3 of 15  ​ Prostaglandin synthesis STIMULATION ○​ Synthesized by the gastric mucosa ​ Receptors on the basolateral membrane ○​ Inhibits gastric secretion ○​ Gastrin and Acetylcholine ○​ Stimulates mucus and HCO3– secretion ​ Increase cytosolic free Ca2+ ○​ Side effects of medications such as pain medications inhibit ○​ Histamine prostaglandin thus causing ulcers ​ Increase intracellular cyclic adenosine monophosphate (cAMP) ​ ex. NSAID-induced gastritis ○​ Net effect = proton pumps from tubulovesicular structures (TV) ​ Gastric mucosal flow to canaliculi ○​ Better vasculature = better healing ​ Proton pumps are under the influence of Gastrin, Histamine, and ​ Epithelial regeneration Acetylcholine ○​ Healing from ulcers ○​ Histamine: strongest agonist ○​ Synergistic action, more than additive ​ High rates of secretion at relatively small changes ​ Markedly inhibited by blocking 1 trigger (H2 blockers that inhibit histamine) Figure 14. Parietal Cells and their Receptors for ACh, Histamine, and Gastrin ​ Proton pumps secrete acid when they are attached to the canaliculi Figure 17. Stomach’s Mucus Mechanism ​ Antral G cell agonists interact with the parietal cell ○​ Antral G cells are stimulated by vagal stimulation (enteric F.​ PHASES OF GASTRIC SECRETION stimulation) by Gastrin-Releasing Peptide (GRP), releasing Table 3. PHASES OF GASTRIC SECRETION Gastrin (G) ​ Gastrin acts on the parietal cell of the stomach to secrete HCl PHASE DESCRIPTION PORTION ​ Gastrin (and acetylcholine) acts on the enterochromaffin-like cell (ECL) to release histamine Cephalic ​ HCl 30% ​Histamine acts on the parietal cell to secrete HCl ​ Intrinsic factor (essential) ​ Acetylcholine from the neuron also reacts with the parietal cell to release HCl Gastric ​ Most important 60% ​ Local nervous secretory reflexes ​ Gastric distention → vagovagal reflex (stomach to brain, brain to stomach) ​ Gastrin-histamine stimulation ​ Presence of food in the stomach would further increase gastric secretion Intestinal ​ Chyme in the duodenum 10% ​ Duodenal gastrin ​ Nervous and hormonal mechanisms increase gastric secretion Figure 15. ACh, Gastrin, and Histamine Stimulate the Parietal Cell D.​ GASTRIC ACID NEGATIVE FEEDBACK ​ Acid can be damaging if NOT controlled ​ When antral pH < 3 (acid too high) → somatostatin is released from D cells in the antral mucosa ○​ Note that the pancreas also has D cell ○​ Somatostatin inhibits gastrin release ​ Negative feedback ​ Somatostatin = killjoy ○​ Can also be seen in other organ systems such as the anterior pituitary of the endocrine system ​ If there is no gastrin → no enterochromaffin cell (ECL) and parietal cell stimulation ○​ No release of HCl Figure 18. Phases of Gastric Secretion G.​ GASTRIC SECRETION SUMMARY Table 4. CELLS OF GASTRIC SECRETION PART OF SECRETION STIMULUS FOR CELL TYPE STOMACH PRODUCTS SECRETION Parietal Body ​ HCl ​ Gastrin Figure 16. Acid in the Antrum Stimulates Somatostatin Release to Inhibit cells (fundus) ​ Intrinsic factor ​ Vagal stimulation Meal-stimulated Gastrin Secretion (essential) (ACh) ​ Histamine E.​ MUCOUS NECK CELLS ​ Produce mucus = stomach’s protection mechanism Chief cells Body ​ Pepsinogen ​ Vagal stimulation ​ Gastric mucus: alkaline mucus layer (fundus) (converted to (ACh) ○​ Lubricant pepsin at low ○​ Protectant against abrasion pH) ○​ Protectant against acids and enzymes ​ Secretes bicarbonate ions (HCO3–) OS 206 GI Secretion and Biliary Secretion / Common GI Tests 4 of 15  G cells Antrum ​ Gastrin ​ Vagal stimulation (via GRP) ​ Small Peptides Inhibitors ​ Somatostatin ​ H+/Low pH of the stomach (via stimulation of somatostatin release) Mucus Antrum ​ Mucus ​ Vagal stimulation cells ​ Pepsinogen (ACh) V.​ PANCREATIC SECRETION ​ Endocrine pancreas ○​ Synthesize hormones ​ Exocrine pancreas ○​ Clear, colorless, alkaline, isotonic secretions ○​ Osmolality constant with flow rate ​ As opposed to salivary secretions which changes ○​ Composition: ​ Organic Figure 21. Pancreatic acinus duct morphology. Enlarged in Appendix. ​Digestive enzymes are usually inactive except amylase, B.​ PANCREATIC SECRETIONS lipase, DNAse, and RNAse ​Trypsin inhibitor - deactivates activated trypsin within the ​ Enzymes pre-formed in the pancreas → exocytosed into pancreatic pancreas duct lumen → pancreatic duct of Wirsung → joins common bile duct ​Colipase - important for bile salt function → Ampulla of Vater → major duodenal papilla ​Other proteins: (e.g., alkaline phosphatase) ​ The sphincter of Oddi (a muscular valve) encircles the duodenal ​ Inorganic papilla which is usually closed ​Cations: Na+, K+, Ca2+, Mg2+ ○​ When stimulated in response to meals, it opens ​Anions: HCO3-, Cl-, SO4- ○​ Enzymes from the pancreas are then secreted into the 2nd ​ Aqueous or HCO3- component (descending) part of the duodenum ​Neutralization of pH PANCREAS AS AN ACINUS AND DRAINING DUCT ​Prevents duodenal mucosal damage by acid ​ Pancreatic cells ​Sets optimal pH for the enzymes to work ○​ Acinar cells ○​ Pancreatic enzyme activity - operates on a higher pH than ​ Synthesize, store, and secrete digestive enzymes stomach ○​ Centroacinar cells ○​ Solubilization of bile salts ​ Electrolyte transport ○​ Micelle formation ​ Contain carbonic anhydrase ​ Enzymatic or protein component ​ Transition between acinar and ductal cells ​Low volume secretion ○​ Ductal cells ​Digestion ​ Secrete bicarbonate ○​ Protein - trypsin, chymotrypsin, carboxypolypeptidase ​ Contain carbonic anhydrase ○​ Carbohydrate - amylase ​ Secretions made in the acinar cells (predominantly enzymes) are ○​ Fat - pancreatic lipase, cholesterol esterase, modified as they pass through the duct (refer to Figure 22) phospholipase ○​ Secreted into the duct: Na+, K+, HCO3-, Cl- ○​ Absorbed: Cl- Figure 19. Pancreas Figure 22. Pancreatic acinus and draining duct CONCENTRATIONS IN PANCREATIC SECRETIONS COMPARED WITH PLASMA ​ Concentration is pretty much constant regardless of the flow ​ Sodium and potassium concentrations are equal to the plasma ​ Bicarbonate concentration is greater than the plasma HCO3- ○​ To neutralize the acid of the stomach ​ Chloride concentration is less than the plasma Figure 20. Pancreas histology - Islet of Langerhans ○​ As bicarbonate increases, chloride decreases A.​ PANCREATIC DUCT MORPHOLOGY ○​ Because Cl- is being absorbed ​ From Doc. Cuaño (Refer to Figure 23) ​ Pancreas → main pancreatic duct → lobules (secretory unit) → ○​ Equal sodium to plasma (red), more bicarbonate than plasma interlobular ducts → intralobular ducts → pancreatic acinar and (orange), less chloride than plasma (green), equal concentration ductal cells (zooming in) of potassium with plasma (dark red) ​ Similar to salivary glands ​ OS 206 GI Secretion and Biliary Secretion / Common GI Tests 5 of 15  - Acts on pancreatic duct cells to produce more HCO3-, neutralizing the stomach acid ​ CCK and secretin are the hormones that dictate what type of hormone secretion should come out of the pancreas Pancreatic Duct Cells ​ Secretin ○​ Stimulated by acid ​ Released if the pH < 4.5 and release bicarbonate to neutralize stomach acid ○​ Opens cystic fibrosis transmembrane conductance regulator (CFTR) ○​ Cl- drives HCO3--Cl- antiporter ​ Favorable gradient for chloride to go in and bicarbonate to go out into the pancreatic duct ○​ Cl out through an active process ​ Result: Concentration gradient becomes favorable for Cl to go back into the duct ○​ Cl- goes back into the duct Figure 23. Pancreatic secretion vs. plasma ​ Results in: ​High concentration in the lumen Note: This section was directly lifted from 2028 Trans. ​Low concentration in the duct cell Sodium bicarbonate secretion [Guyton] ○​ HCO3- excreted into the duct ​ Carbon dioxide (CO2) from metabolism joins water to form ​ Increases pH of the ductal secretion to: carbonic acid (H2CO3) in the pancreatic duct cell, which ​Increase pH of duodenum dissociates to form bicarbonate (HCO3-) and hydrogen (H+) ​Neutralize pH of gastric secretion ○​ In the presence of carbonic anhydrase (CA) ​ The H+ formed by dissociation of carbonic acid inside the cell is exchanged for Na+ through the basolateral membrane of the cell by secondary active transport ○​ Sodium ions also enter the cell by cotransport with bicarbonate across the basolateral membrane ​ Sodium ions are then transported across the luminal border into the pancreatic duct lumen ○​ The negative voltage of the lumen also pulls the positively charged Na+ across the tight junctions between the cells ​ The overall movement of Na+ and bicarbonate ions from the blood into the duct lumen creates and osmotic pressure gradient that causes osmosis of water also into the pancreatic duct ○​ Forms an almost completely isosmotic bicarbonate solution PHASES OF PANCREATIC SECRETION Table 5. PHASES OF PANCREATIC SECRETION PHASE DESCRIPTION PORTION Cephalic Sight and scent of food; vagus and 20% muscarinic cholinergic receptors Gastric Food in the stomach; vagovagal and 5 - 10% gastrin release Figure 25. Pancreatic duct cells (left side: lumen; right side: interstitial space) HCO3- sources Intestinal Food is in the intestines; most 80% ​ You can’t get bicarbonate out of nothing important for pancreatic secretions ​ HCO3- from alkaline tide through NBC-1 ○​ Alkaline tide ​ Food initially in the stomach is acidic, proteins and fat are partially ​ Transient increase in blood pH due to HCO3- digested → goes to the duodenum (food is still a little acidic) ​Parietal cell secretes HCl into the gastric lumen →​Acid stimulates the secretion of secretin by the duodenal S cells ​Since it is losing proton, it has to secrete HCO3- into the →​Protein and fat stimulate the secretion of cholecystokinin from bloodstream the duodenal I cells ○​ To maintain intracellular pH ○​ NBC-1 = sodium-carbonate cotransporter ​ HCO3- goes in ​Supplies the HCO3- needs of the ductal cells ​ Intracellularly from carbonic anhydrase ○​ Products of metabolism cause an increase in CO2 ​ Becomes carbonic acid (H2CO3) when mixed with water ○​ Carbonic anhydrase ​ Breaks down carbonic acid (H2CO3) into bicarbonate (HCO3) Pancreatic Acinar Cells ​ Cholecystokinin (CCK) ○​ Stimulated by high protein and high fat content ​ Leads to the exocytosis of pancreatic enzymes to digest protein and fat ​ End result: CCK acts on acinar cells ​Causes the release of enzymes into the duodenum ​ Direct Action of CCK on receptor ○​ Causes an increase in calcium ions ​ Leads to the exocytosis of the enzymes, digestion of fat and protein Figure 24. Pancreatic secretions ​Preformed granules that contain enzymes attach to the Table 6. Cholecystokinin vs secretin apical membrane and are released to the pancreatic duct ​ Indirect Action of CCK Cholecystokinin (CCK) Secretin ○​ Vagovagal stimulation leading to release of VIP, GRP, ACh ​ Acts on vagal receptors Secreted by I cells Secreted by S cells ​ Release of neurotransmitters ​ VIP = Vasoactive intestinal polypeptide Low output pancreatic High volume H2O, Weak protein ​ GRP = Gastrin-releasing peptide secretion, High Protein secretion ​ ACh = Acetylcholine ○​ Leads to exocytosis of preformed enzymes into the pancreatic duct Low HCO3- High HCO3 OS 206 GI Secretion and Biliary Secretion / Common GI Tests 6 of 15 ​ VIP increases cAMP and GRP, ACh, and CCK increase in calcium ○​ Protect the duodenal wall from digestion by gastric acid = increased in calcium inside the cell ​ Secretes enterokinase ○​ Causing the fusion of the preformed granules to the apical ○​ Found in the small intestine membrane and the release of the enzyme into the ducts ○​ Activates pancreatic enzymes ​ Secretin also acts on acinar cells but NOT as significantly as its ​ Trypsinogen into trypsin action on ductal cells ○​ How can the pancreas NOT destroy itself despite containing digestive enzymes? ​ Stores enzymes as proenzymes ​ Proenzymes must be exposed to enterokinase in the small intestine to be activated Figure 26. Pancreatic acinar cells REMEMBER [2027 Trans] Secretin: Duct Cells = CCK: Acinar Cells Pancreatic Duct Cells ○​ Secretin opens CFTR → Cl out → Cl in → HCO3- out Integrated Action of Gastric and Pancreatic Secretions ​ Food in the stomach ○​ Causes gastrin secretion ○​ From Doc: Nakikita mo pa lang yung food may secretions na agad ​ Gastrin ○​ Acts on parietal cells and enterochromaffin-like cells Figure 28. Brunner’s Glands ○​ Increase acid secretion and motility SECRETION OF THE CRYPTS OF LIEBERKUHN ​ Enterochromaffin-like cells ○​ Produce histamine ​ Succus entericus (intestinal juice) ​ Histamine ○​ water, mucus, electrolytes, enzymes ​Acts on parietal cells ​ Serves as the vehicle of the absorption of the substances that ​Result: increase in acid secretion come into contact with the villi ​ From the stomach, food and acid go into the duodenum ​ Produced by epithelial cells in the crypt ​ CCK and secretin secretion ​ Secrete 1L per day, pH 7.5-8.0 (alkaline) ○​ CCK ​ Rapidly absorbed in the villi ​ Stimulated by protein and fat ​ Helps in digestion ​ Cause release of enzymes ​ Active transport of Cl- and HCO3- drags Na+ and H2O [2026 Trans] ○​ Secretin ​ Crypt cells mature into villar cells near the lumen [2026 Trans] ​ Stimulated by acid ○​ Crypt cells are for secretion ​ Cause release of bicarbonate ○​ Villar cells are for absorption ​ Both CCK and secretin secretion cause pancreatic and biliary secretions resulting in the intestinal digestion of food Figure 29. Crypts of Lieberkuhn SECRETION REGULATION ​ Stimulated by: ○​ Vagal stimulation (parasympathetic) ○​ Tactile or irritating stimuli ○​ Local stimuli ○​ Chyme in the intestine ○​ Hormonal regulation (CCK and Secretin) ​ Inhibited by: ○​ Sympathetic stimulation ​ Patients with diarrhea are sometimes given sympathetic agents to control defecation B.​ LARGE INTESTINE SECRETION ​ Mucus secretion ○​ Stimuli: ​ Tactile stimulation ​ Presence of food ​ Parasympathetic stimulation ○​ Stimulate secretion of large intestine Figure 27. Gastric and pancreatic secretions ○​ Protect against excoriation ○​ Hold fecal matter together VI.​ INTESTINAL SECRETION ○​ Protect against bacterial activity and acid formed in the feces ​ Water and electrolytes A.​ SMALL INTESTINE SECRETION ○​ Produce a lot of water and electrolytes to dilute the irritating SECRETION OF THE BRUNNER’S GLAND factors of the bacteria, e.g. enterocolitis ​ Antidiarrheals are not given to evacuate colonic contents ​ Submucosal mucous glands in the duodenal bulb (alkaline) ​ Manual extraction is sometimes performed in case of impaction ○​ Secretions must be alkaline because the duodenal bulb is the first to be exposed to acidic gastric secretions ​ Function OS 206 GI Secretion and Biliary Secretion / Common GI Tests 7 of 15  VII.​ BILIARY SECRETION ZONE 1 ZONE 3 A.​ LIVER Periportal - closest to blood Pericentral or source Centrilobularclosest HEPATIC BLOOD FLOW to central vein ​ Steps for hepatic blood flow: ○​ Oxygenated blood from the hepatic artery + Nutrient-rich 1st to receive O2, nutrients, Last to change in bile duct deoxygenated blood from the portal vein toxins because it is closest to obstruction and exposure ○​ Liver sinusoids (spaces between the liver lobules) vasculature to toxins, because it is far ○​ Central vein from the vasculature ○​ Hepatic Vein ○​ Inferior Vena Cava Sensitive to Oxidative injury Sensitive to Ischemia ○​ Right Atrium of the Heart Because closest to Because it is far from the vasculature vasculature Most active in detoxification Most active in bile acid synthesis 1st to take excess glucose 1st in fat accumulation to glycogen & vice versa LIVER FUNCTION Table 8. LIVER FUNCTION CATEGORIES AND ACTIONS FUNCTIONAL ACTION CATEGORY Detoxification Phagocytosis by Kupffer cells of Blood Chemical alteration of biologically active molecules (hormones and drugs) Production of urea, uric acid, and other molecules that are less toxic than parent compounds Excretion of molecules in bile Carbohydrate Conversion of blood glucose to glycogen and Metabolism fat Production of glucose from liver glycogen and from other molecules (amino acids, lactic acid) by gluconeogenesis Secretion of glucose into the blood Figure 30. Hepatic Blood Flow Lipid Synthesis of triglyceride and cholesterol Metabolism Excretion of cholesterol in bile LIVER LOBULE Production of ketone bodies from fatty acids ​ Branch of portal vein + hepatic vein → Drains into the liver sinusoids → Drains into the central vein Protein Production of albumin ​ Contents of the sinusoidal lumen: Synthesis Production of plasma transport proteins ○​ Stellate cells (Ito cells) Production of clotting factors (fibrinogen, ○​ Endothelium prothrombin, and others) ○​ Kupffer cells ○​ Space of Disse Secretion of Synthesis of bile salts ​ A layer of loose connective tissue where stellate cells are Bile Conjugation and excretion of bile pigment located. (bilirubin) ​ Hepatocytes ○​ Cells that produce bile ​ Contents of the Hepatocyte *Our focus is on the secretion of bile only. ○​ Bile canaliculi BILIARY SECRETION ​ The channel between opposed apical membranes ​ Hepatocytes synthesize bile. ​ Drains bile from the liver to the bile ducts ​ 600 to 1000 ml/day ○​ Bile duct ​ 2 important functions: ​ Attached through the sinusoids ○​ Fat digestion and absorption: Bile Acids (digestion) ​ Emulsify fat particles into minute particles ​ Absorption of the digested fat end products through the intestinal mucosal membrane ​ Bile Acids are for digestion ○​ Excretion of waste products from the blood: Bilirubin (excretion) ​ End product of HgB destruction ​ Cholesterol ​ Bilirubin is for excretion ​ Bile acids are both: ○​ Synthesized by hepatocytes ○​ Extracted from incoming blood ○​ Eventually, pass into the bile duct and is stored/concentrated in the gall bladder Figure 31. Liver Lobule LIVER PARENCHYMA ARCHITECTURE ​ Liver Lobule ○​ Anatomic Unit of the Liver ​ Acinus ○​ Functional Unit of the Liver ○​ Related to the portal triad ​ The liver lobule is divided into three zones ○​ The location of the zones would impact how they respond to stimuli ○​ Arranged in proximity to the portal and hepatic vein Table 7. DIFFERENCES BETWEEN ZONE 1 AND ZONE 3 Figure 32. Functional Unit of the Liver OS 206 GI Secretion and Biliary Secretion / Common GI Tests 8 of 15  BILE ACID PRODUCTION ​ “Cholecystokinin” = moves the gallbladder ​ Cholesterol Diffuses into hepatocytes →​Cholecystokinin: gallbladder ​ Cholesterol is catabolized into Cholic Acid or Chenodeoxycholic acid →​Kinin: movement ○​ Primary bile acids because hepatocytes synthesize them →​For Gallbladder contraction and Sphincter of Oddi ○​ Acted by 7α hydroxylase (a rate-limiting step) relaxation ​ Conjugated with Glycine or Taurine (Hepatocyte) ​ Bile flows toward duodenum ○​ Forms Bile Salts →​Causes pancreatic acinar cells to produce enzymes and ​ Converted into Secondary bile acids by colonic bacteria proteins ○​ Occurs in the colon →​Has vagal stimulation ​ Conjugated bile acids are secreted into the biliary tree ▪​ Further contributes to gallbladder contraction; thus, bile → ○​ Becomes ionized once conjugated → Cannot diffuse through duodenum the membranes ​ Secretin ○​ Negative charge by glycine and taurine will increase the solubility →​Increase bicarbonate by stimulating pancreatic of BA in water and cannot diffuse to the phospholipid bilayer duct cells/ ductal secretion (locking it in) BA itself also impacts biliary secretion ○​ Have to be uptaken at the terminal ileum by Apical Sodium Dependent Bile Salt Transporter Figure 35. Regulation of Biliary Secretion ​ Passive Diffusion ○​ Tight Junctions are Leaky ○​ Driven by osmotically active substances (Bile Acids, Phosphatidylcholine, conjugated bilirubin, Xenobiotics) ○​ Concentrations approximate plasma Figure 33. Mechanism of Bile Acid Production Nice to Know ​ Doc Cuaño said that Bile Acid Production will not be included in the exam. BILE ACIDS VS. BILE SALTS ​ Bile Salts = Bile acids conjugated with Glycine or Taurine ​ Conjugation ○​ Bile acids are water-soluble ○​ Important because digestion takes place in the Aqueous environment ○​ Cannot passively diffuse through the intestinal epithelium Figure 36. Passive Diffusion in Hepatocytes BILIARY SECRETION CONTROL ​ Canalicular Bile secretion ○​ Bile Acid Dependent ​ ↑ Bile Acids in Blood ​(↑) Bile acid secretion : (↑) Ileal Bile Acid Transporters ​(↓) Bile acid synthesis ○​ Bile Acid Independent ​ Ductural Bile Secretion Figure 34. Conjugation of Bile Acids. Enlarged in Appendix. ○​ Secretin ​ (↑) H20 : (↑) HCO-3 BILIARY SECRETION ○​ Somatostatin ​ Bile acids via blood stimulate parenchymal secretion ​ (↓) H20 : (↓)HCO-3 ○​ It occurs if we have a lot of bile acid in the blood, causing ​ Total bile flow = ductular secretion + canalicular bile secretion hepatocytes to secrete bile acids. ​ Canalicular bile secretion comes from the hepatocytes ​ Secretin via the bloodstream stimulates the liver ductal secretion ○​ Two types: bile-acid-dependent and independent ○​ This causes bile acids to be secreted into the bile duct ○​ Bile-acid independent flow and ductular secretion are fixed ​ Bile is stored and concentrated up to 15 times in the gallbladder ○​ Bile-acid dependent flow is NOT fixed ​ Cholecystokinin via the bloodstream causes: ​ Depend on the amount of bile acid that your body has ○​ Gallbladder contraction ​ Inc BA in blood ​ Bile acids/salts will then go down the biliary tree ​Inc BA secretion → inc BA transporters ○​ Relaxation of the sphincter of Oddi ​Dec BA synthesis ​ Bile acids/salts will enter the first part of the duodenum ​ Ductular secretion comes from the cholangiocytes ○​ Modified by: ​ Secretin: increase H2O and HCO3 ​ Somatostatin: decrease H2O and HCO3- (inhibitor) ​ Modification by gallbladder (GB): concentrates, acidifies, stores (when fasting), and discharges bile (when eating) via CCK Remember ​ Somatostatin is the ultimate KJ (killjoy). B.​ GALLBLADDER OS 206 GI Secretion and Biliary Secretion / Common GI Tests 9 of 15  FUNCTIONS OF THE GALLBLADDER ○​ Stimulated: By fatty acids and hydrolyzed proteins ○​ Effect ​ Storage: In between meals (25-50 cc) ​ Gall Bladder Contraction ​ Concentration: Through reabsorption of water (5-20x) ​ Sphincter of Oddi (SO) Relaxation ​ Release: By contraction in response to: ​ Vagal Afferents ○​ CCK: Considered to be the most potent stimuli ○​ Action of CCK (direct VS indirect) ​ Stimuli: Include proteins and fats in the small intestine ○​ Cephalic and Gastric Phases ○​ Vagal Stimulation ​ Through cephalic and gastric phases ENTEROHEPATIC CIRCULATION BILIARY SECRETION CONTROL ​ Bile Salts and Acids: ○​ Difficult to produce so the body can recycle them through ​ Composition of Bile enterohepatic circulation ○​ Gallbladder bile contents such as bile salts, bilirubin, cholesterol, ○​ Recycling of bile after each meal fatty acids, and lecithin increased compared to the bile ​ Process: produced by the liver 1.​ Starts with bile salts being produced by the liver (from the ○​ On the other hand, electrolytes such as sodium, chloride, and gallbladder) bicarbonate were observed to have decreased compared to liver 2.​ Concentrated in the gallbladder bile 3.​ Secreted into the 2nd part of the duodenum where they help with Table 9. SUMMARY OF BILE COMPOSITION emulsification of fat (making fat more soluble and through micelle formation) LOWER HIGHER (CONCENTRATED) ○​ Duodenum: Can partially absorb bile acid ​ Water ​ Bile Salts ○​ Ileum (Terminal): Absorbs MOST of the bile acid →​Water was reabsorbed →​Since water was ​ By the time they reach this part, intestinal bacteria →​Osmosis: Where sodium reabsorbed deconjugate and dehydroxylate the bile acids to produce goes (going outside), ​ Bilirubin secondary bile acids water follows ​ Fatty Acids ​Deoxycholic Acid: Eventually reabsorbed in the ileum and →​It passes through ​ Lecithin goes back to the liver through portal circulation (recycling) aquaporins ​Lithocolic Acid ​ Sodium ​ursodeoxycholic acid →​Due to Na-H exchanger ​ The only bile acids we have to produce are the bile acids that are ▪​ In: Hydrogen lost (5%) ▪​ Out: Sodium ○​ Hepatic Synthesis: Makes up for the lost bile acids ​ Chloride →​Due to a transporter ​ Bicarbonate Table 10. COMPOSITION OF BILE SUBSTANCE LIVER BILE GALLBLADDER Water 97.5 g/dl *92 g/dl *Bile Salts 1.1 g/dl 6 g/dl Bilirubin 0.04 g/dl 0.3 g/dl Cholesterol 0.1 g/dl 0.3 to 0.9 g/dl Fatty Acids 0.12 g/dl 0.3 to 1.2 g/dl Lecithin 0.04 g/dl 0.3 g/dl Sodium (Na+) 145 mEq/L *130 mEq/L Potassium (K+) 5 mEq/L 12 mEq/L Calcium (Ca2+) 5 mEq/L 23 mEq/L Chloride (Cl-) 100 mEq/L *25 mEq/L Figure 38. Movement of bile through different organs Bicarbonate (HCO3-) 28 mEq/L *10 mEq/L BILIRUBIN ​ Waste Product: From old/senescent RBC taken up by *Emphasized by Doc Cuaño. reticuloendothelial system ​ Process of Bilirubin Flow ○​ Old RBC are taken up by Kupffer cells and cells from the reticuloendothelial system ​ Hemoglobin is broken down into heme and globin ​Iron: Recycled ​Heme: Eliminated ​ Heme is converted to bilirubin by the reticuloendothelia cells ○​ Since bilirubin is hydrophobic, it cannot be bound freely in the bloodstream so it is bound to albumin ○​ Bilirubin is transported to liver ​ Since it is hydrophobic, it can freely diffuse into the liver ​Hepatocytes take up the bilirubin ○​ Liver conjugates the bilirubin with glucoronic acid using glucuronosyltransferase ​ End Product: Conjugated Bilirubin (hydrophilic) ​ Unconjugated VS Conjugated ○​ Unconjugated Bilirubin: Lipid-soluble, needs to be bound to albumin ○​ Conjugated Bilirubin: Water-soluble, bound to glucuronic acid, charged Figure 37. Cholangiocytes BILE FLOW ​ CCK (Cholecystokinin) ○​ Released by Duodenal I cells Figure 39. Flow of Bilirubin. Enlarged in Appendix. OS 206 GI Secretion and Biliary Secretion / Common GI Tests 10 of 15  BILIRUBIN METABOLISM ○​ 10:3:1 Ratio: Proper proportions of bile acids, lecithin, and cholesterol that prevent cholesterol precipitation and gallstone ​ Fragile RBCs are taken up by the reticuloendothelial system formation ​ Heme converted biliverdin ​ If you have too much cholesterol, it could affect the ratio ○​ By heme oxygenase needed to maintain the liquid state of bile and promote ​ Biliverdin converted to unconjugated bilirubin gallstone formation ○​ By biliverdin reductase ○​ Cholesterol VS Pigment Gallstone ○​ Recall: Unconjugated = Hydrophobic (water-insoluble) ​ Pigment Gallstone: Found in Asian countries that do NOT ​ Unconjugated bilirubin is bound to albumin follow the Western diet ○​ Then goes to the liver where it is taken up ​ Cholesterol Gallstone: Found in diet with high cholesterol ​ Unconjugated bilirubin conjugated to glucuronic acid to form ​Even though the Filipinos are Asian, they follow a Western bilirubin glucuronide (by UGT or UDP-Glucuorosyltransferase) diet ○​ Recall: Conjugated = Hydrophilic (water-soluble) ○​ Even a single stone can impinge the common hepatic or bile duct ​ Goes into the duodenum upon which some bacteria act on it, producing urobilinogen and stercobilinogen can cause hyperbilirubinemia and thus, cause jaundice (conjugated ○​ Urobilinogen: Can go to the bloodstream and kidneys and be type) secreted by the urine ​ Hyperbilirubinemia ○​ Stercobilinogen: Oxidized into stercobilin and went to the ○​ Recall: Increase in bilirubin is NOT just caused by obstruction of stomach, eventually ending up in the feces (giving the feces its biliary tree characteristic color) ○​ Hemolytic Anemia: Indirect Hyperbilirubinemia ​ Results in a lot of heme since the RBCs keep on lysing, causing an increase in unconjugated bilirubin ​The liver has difficulty conjugating all of the unconjugated bilirubin, causing jaundice ○​ Hepatitis ​ Results in damaged liver, causing it to have difficulty in conjugating bilirubin and excreting bile into canaliculi in the ducts ​Causes an increase in BOTH conjugated and unconjugated bilirubin ○​ Biliary Duct Stone ​ The liver still has normal function and conjugates bile properly BUT there is an obstruction in the biliary tree, preventing the exit of bile ​Results in an increase of conjugated bilirubin ​ Jaundice in Newborns ○​ During the first week of life, production of UDP-glucuronosyltransferase is delayed, causing an increase in unconjugated bilirubin Figure 40. Bilirubin formation and excretion ​ Treatment: Exposure to Sunlight ​Unconjugated bilirubin is photosensitive, so it is irradiated Simpler Process of Bilirubin Metabolism with blue light, to lyse it ​ Starts with heme → biliverdin → bilirubin-albumin complex (unconjugated) → conjugated in liver → becomes bilirubin glucuronide → secreted into bile ducts → acted on by colonic bacteria and unconjugated in the colon → becomes urobilinogen and stercobilin in the stool and urine Figure 42. Pigment gallstones (L) VS Cholesterol gallstones (R) Figure 41. Bilirubin metabolism BILIRUBIN IN BLOOD AND URINE Figure 43. Cholesterol gallstones Table 12. SUMMARY OF HYPERBILIRUBINEMIA Table 11. UNCONJUGATED VS. CONJUGATED BILIRUBIN HEMOLYTIC BILIARY DUCT PRESENT HEPATITIS FRACTION IN SERUM AS MEASURED AS ANEMIA STONE IN URINE Unconjugated Indirect-reacting ↑↑↑ ↑ Unconjugated Albumin-bound Never Bilirubin bilirubin Conjugated Yes, when ↑ ↑↑↑ serum Bilirubin Direct-reacting Conjugated Unbound bilirubin bilirubin level > 3-4 CASE EXERCISES mg/dl 1.​ Hyperbilirubinemia can be accompanied by bilirubinuria, resulting in tea-colored urine. In which of the following CLINICAL APPLICATION conditions is bilirubinuria NOT likely to occur? ​ Gallstones A.​ Blood transfusion reaction (will not get ○​ Appears pale in color bilirubinuria because this is a hemolytic reaction ○​ Causes so it increases the pool of unconjugated bilirubin) ​ Too much absorption of water from bile B.​ Choledocholithiasis (obstructive to bile duct, increase ​ Too much absorption of bile acids from bile in conjugated) ​ Too much cholesterol in bile C.​ Hepatitis B infection (increase in both) ​ Inflammation of epithelium OS 206 GI Secretion and Biliary Secretion / Common GI Tests 11 of 15  ​ Its primary function is to remove phosphate groups from the D.​ Pancreatic CA (obstructive to bile duct, increase in nucleotides, proteins, and alkaloids conjugated) ​ 80% is found in the liver, however, 20% is also found in the bone 2.​ If bile flow into the duodenum is obstructed, which of the ○​ It is also present in placenta, kidneys, leukocytes, bile duct following is expected to occur? epithelia A.​ Increased gastrin secretion ○​ Found to be higher in children and pregnant women B.​ Decreased motility of colon ​ If you have cholestatic injury, this will cause an accumulation of C.​ Increased conjugated bilirubin bile acids, resulting in elevation of the ALP D.​ Decreased intestinal absorption of glucose ○​ Common causes: ​ defect in bile formation by hepatocytes VIII.​ LIVER TESTS ​ impairment in bile secretion and flow ​ Performed for the following reasons: ○​ Overall result: ○​ Detect hepatic dysfunction ​ increase in ALP synthesis ○​ Assess severity ​ Levels of ALP are abnormal in the following: ○​ Monitor liver diseases in response to treatment ○​ e.g. choledocholithiasis, pancreatic CA, cholangio CA, Paget’s ○​ Refine the diagnosis disease of the bone (osteoblast activity) Table 13. COMMON LIVER TESTS ​ Remember that ALP is also found in the bone, and as such, elevated levels of ALP are not only liver-related and can be Hepatocellular indicative of bone-related disease Alanine aminotransferase (ALT/SGPT) ​ This makes it less specific than GGT tests Aspartate aminotransferase (AST/SGOT) GAMMA GLUTAMYL TRANSFERASE (GGT/GGTP) Cholestatic ​ Aka gamma-glutamyl transpeptidase (GGTP) ​ Metabolizes glutathione Alkaline Phosphatase (ALP) ○​ Transfers a gamma-glutamyl group from glutathione (a tripeptide Gamma glutamyl transferase (GGT/GGTP) antioxidant) and other gamma-glutamyl peptides to other amino Serum Bilirubin acids or peptides Other Common Tests ​ It is a more specific indicator: ○​ found in hepatocytes, biliary epithelial cells, renal tubules, Direct and Indirect Bilirubin pancreas, and intestines Protein: Albumin and Globulin Prothrombin Time Example Case: A patient presents with the following: IX.​ LIVER DISEASE CLASSIFICATION AND MARKERS ​ Elevated ALP A.​ HEPATOCELLULAR ​ Clear liver, normal ultrasound ​ Normal ALT and AST ​ Affects the hepatocytes ○​ There is liver inflammation, necrosis A GGT test is done to be sure of the cause: ​ Related to entities that attack the liver hepatocytes ​ Bone-related disease will present with high ALP but low GGT ○​ e.g. Viral hepatitis, alcoholic liver disease, ischemic hepatitis, drug-induced liver damage ​ GGT is also elevated in people with the following: ​ You expect elevated levels of ALT and AST ○​ alcohol liver disease, COPD, renal failure, acute MI, cholestasis ○​ these are enzymes in the liver that leak out into the blood when ​ The isolated elevation of GGT is a marker of chronic alcohol there is liver damage consumption with or without underlying liver disease ○​ results of GGT levels are correlated with ALP levels to confirm Information for Understanding: liver origin ​ Alanine aminotransferase (ALT) is also known as serum glutamic ​ Serum Bilirubin is also tested pyruvic transaminase (SGPT) C.​ MIXED ○​ It’s main function is to facilitate the transfer of an α-amino group from alanine to ketoglutaric acid to form pyruvate or ​ A mixture of both hepatocellular and cholestatic injury glutamate ○​ e.g. Cholestatic form of viral hepatitis, DILI ​ Aspartate aminotransferase (AST) is also known as serum ​ Elevated AP, ALT, AST glutamic oxaloacetic transaminase (SGOT) D.​ INFILTRATIVE ○​ It’s primary function is similar to ALT: to catalyze the transfer of ​ Related to diseases such as malignancy (lymphoma), an α-amino group from aspartate to alpha-ketoglutarate to amyloidosis, and sarcoidosis form oxaloacetate and glutamate ​ Findings: ○​ Oxaloacetate and oxaloacetic acid are essentially the same ○​ Elevated alkaline phosphatase more than transaminases molecule but differ in their protonation state: ○​ Near-normal AST, ALT ​ Oxaloacetic acid is the protonated (neutral) form ○​ Total and direct bilirubin not very high ​ Oxaloacetate is the anionic form X.​ MARKERS OF LIVER FUNCTION & PROTEIN SYNTHESIS ​ De Ritis ratio ○​ Given by the following equation: AST/ALT A.​ SERUM ALBUMIN ​ Provides more information on what kind of hepatocellular ​ Most abundant protein in the plasma, which is synthesized condition is present exclusively by the liver Table 14. INDICATION OF DE RITIS RATIO VALUES ​ Hepatocytes synthesize: ○​ Albumin globulin (except gamma) and; Value Indication ○​ Clotting factors (except Factor 8) Most liver conditions (e.g. viral hepatitis, ​ Normal range: Albumin is 3.5-5.5 g/dL Ratio < 1 ​ Decreased albumin → chronic liver disease Non-Alcoholic Steatohepatitis (NASH)*)