Gastrointestinal Physiology

• -GI structures that lack a mesentery
• -non-GI structures

**injuries to retroperitoneal structures can cause blood or gas accumulation in the RP space

• "SAD PUCKER"
• Suprarenal (adrenal) gland
• Aorta and IVC
• Duodenum (2nd and 3rd parts)
• Pancreas (except tail)
• Ureters
• Colon (descending and ascending)
• Kidneys
• Esophagus (lower 2/3)
• Rectum (lower 2/3)

• Falciform
• -connects liver to abdominal wall
• -contains ligamentum teres hepatis (fetal umbilical vein)
• -derivative of ventral mesentery

• Hepatoduodenal:
• -connects liver to duodenum
• -contains portal triad
• -connects greater and lesser sacs
• **Pringle Manuever: ligament may be compressed btwn thumb and index finger placed in omental foramen to control bleeding

• Gastrohepatic:
• -connects liver to lesser curvature of stomach
• -contains gastric arteries
• -separates greater and lesser sacs on the right
• **may be cut during surgery to access lesser sac

• Gastrocolic:
• -connects greater curvature of stomach and transverse colon
• -contains gastroepiploic arteries
• -part of greater omentum

• Gastrosplenic:
• -connects greater curvature of stomach to spleen
• -contains short gastrics, left gastroepiploic vessels
• -separates greater and lesser sacs on the left

• Splenorenal:
• -connects spleen to posterior abdominal wall
• -contains splenic artery and vein, tail of pancreas

Gi tract has two surfaces: mucosal (faces lumen) and serosal

• Inside to Outside - MSMS
• 1. Mucosa
• -epithelium (absorption)
• -lamina propria (support)
• -muscularis mucosa (motility)

• 2. Submucosa
• -includes Submucosal nerve plexus (Meissner's)

• 3. Muscularis externa
• -includes Myenteric nerve plexus (Auerbach's)

• 4. Serosa
• -when intraperitoneal
• -called adventitia when retroperitoneal

• Ulcers:
• -can extend into the submucosa, inner, or outer muscular layer

• Erosions:
• -in the mucosa only

-determines the frequency of contractions

-frequency varies throughout the digestive system

• Stomach: 3 waves/min
• Duodenum: 12 waves/min
• Ileum: 8-9 waves/min

• Esophagus:
• 
• -non-keratinized stratified squamous epithelium

• Stomach:
• 
• -gastric glands

• Duodenum:
• 
• -villi and microvilli (increase absorptive surface)
• -Brunner's Glands (submucosa) (produce mucus secretions with HCO3- to neutralize stomach acid)
• -Crypts of Lieberkuhn (intestinal glands, contain paneth cells and stem cells)

• Jejunum:
• 
• -Plicae circulares
• -crypts of Lieberkuhn

• Ileum:
• 
• -Peyer's patches (lamina propria/submucosa)
• -plicae circulares (proximal)
• -crypts of Lieberkuhn
• *largest number of goblet cells in SI

• Colon:
• 
• -crypts but NO VILLI-numerous goblet cells

Arteries supplying GI structures branch ANTERIORLY

Arteries supplying non-GI structures branch LATERALLY

• Foregut:
• -Celiac Artery
• -PS Innervation: vagus
• -Vertebral level T12/L1
• -stomach to proximal duodenum, liver, gallbladder, pancreas, spleen (mesoderm)

• Midgut:
• -SMA
• -PS Innervation: Vagus
• -Vertebral level: L1
• -distal duodenum to proximal 2/3 of transverse colon

• Hindgut:
• -IMA
• -PS Innervation: pelvic
• -Vertebral level: L3
• -distal 1/3 of transverse colon to upper portion of rectum
• -splenic flexure is a watershed region

• Branches:
• -Common Hepatic
• -Splenic
• -Left Gastric
• **main blood supply to stomach

Short gastrics have poor anastamoses if splenic artery is blocked

• Strong Anastamoses:
• -L and R gastroepiploics
• -L and R gastrics

-if branches off the abdominal aorta are blocked these anastamoses can compensate:

1. Superior epigastric (internal thoracic) --> Inferior epigastric (external iliac)

2. Superior pancreaticoduodenal (celiac trunk) --> inferior pancreaticoduodenal (SMA)

3. Middle colic (SMA) --> left colic (IMA)

4. Superior rectal (IMA) --> middle and inferior rectal (internal iliac)

• 
• 1. Esophagus
• -esophageal varices
• -L Gastric (Portal) --> Esophageal (Systemic)

• 2. Umbilicus
• -Caput medusa
• -Paraumbilical (Portal) --> Superficial and inferior epigastric below umbilicus, superior gastric and lateral thoracic above the umbilicus (Systemic)

• 3. Rectum
• -internal hemorrhoids
• -superior rectal (Portal) --> Middle and inferior rectal (Systemic)

Varices of the gut, butt and caput commonly seen with portal hypertension

• Treatment:
• -TIPS between portal vein and hepatic vein --> shunts blood to systemic circulation

• 
• AKA: Dentate Line
• -formed where the endoderm (hindgut) meets ectoderm

• Above pectinate line
• -internal hemorrhoids
• -adenocarcinoma
• -superior rectal artery (IMA)
• -superior rectal vein (IMV --> portal system)
• -lymphatic drainage to deep nodes
• **Internal hemorrhoids receive visceral innervation (NOT PAINFUL)

• Below Pectinate Line
• -external hemorrhoids
• -squamous cell carcinoma
• -inferior rectal artery (internal pudendal artery)
• -inferior rectal vein (internal pudendal vein --> internal iliac vein --> IVC)
• -lymphatic drainage to superficial inguinal nodes
• **External hemorrhoids receive somatic innervation (inferior rectal branch of pudendal nerve) and are PAINFUL

• 
• -apical surface of hepatocytes faces bile canaliculi
• -basolateral surface of hepatocytes faces sinusoids

• 
• Zone I:
• -periportal zone
• -affected 1st by hepatitis virus

• Zone II:
• -intermediate zone

• Zone III:
• -pericentral vein (centrilobular) zone
• -affect 1st by ischemia
• -contains p450 system
• -most sensitive to toxic injury
• -site of alcoholic hepatitis

• 
• Gallstones that reach the common channel at the ampulla of Vater can block both the bile and pancreatic ducts

Tumors that arise in the head of the pancreas (near duodenum) can cause obstruction of the common bile duct

• "You go from lateral to medial to find your NAVEL"
• Nerve
• Artery
• Vein
• Empty space
• Lymphatics

• Femoral Triangle
• -contains femoral vein, artery nerve
• -"venous near the penis"

• Femoral Sheath:
• -fascial tube 3-4 cm below inguinal ligament
• -contains femoral vein, artery and canal (deep inguinal lymph nodes)
• -does NOT contain femoral nerve

• -produces an inherent weakness in the abdominal wall
• -due to gonadal development (ovaries and testes descend)
• -Male: testes, vessels, ducts, nerves pass through inguinal canal
• -Female: round ligament of the uterus passes through inguinal canal

• -during development a peritoneal pouching called the processus vaginalis forms
• -if the obliteration of the processus vaginalis is incomplete there is a weakness in the abdominal wall --> increased risk of hernias

-protrusion of the peritoneum through an opening, usually a site of weakness

• Types:
• 1. Diaphragmatic hernia
• 2. Indirect inguinal hernia
• 3. Direct inguinal hernia
• 4. Femoral hernia

• -abdominal structures enter the thorax
• -may occur in infants due to defective development of pleuroperitoneal membrane

• Hiatal Hernia
• -most common
• -stomach herniates upward through the esophageal hiatus of the diaphragm
• -two types: sliding and paraesophageal

• 1. Sliding Hiatal Hernia:
• -most common
• -GEJ displaced upward
• -"hour glass stomach"
• 

• 2. Paraesophageal Hernia
• -GE junction is normal
• -fundus protrudes into the thorax
• 

-goes through the internal (deep) inguinal ring, external (superficial) inguinal ring and into the scrotum

-enters the inguinal ring LATERAL to inferior epigastric artery

• -occurs in infants owing to failure of processus vaginalis to close (can form hydrocele)
• -much more common in males

-an indirect hernia follows the path of descent of the testes (covered by all three layers of spermatic fascia)

• 
• "MDs don't LIe"
• Medial to inferior epigastric artery = Direct hernia
• Lateral to inferior epigastric artery = Indirect hernia

-protrudes through the inguinal (Hesselbach's) triangle

-bulges directly through abdominal wall MEDIAL to inferior epigastric artery

-goes through the external (superficial) ring ONLY

-covered by external spermatic fascia

• -usually in older men
• 

• "MDs don't LIe"
• Medial to inferior epigastric artery = Direct hernia
• Lateral to inferior epigastric artery = Indirect hernia

-protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle

-more common in women

-leading cause of bowel incarceration

-inguinal triangle

• Borders:
• -inferior epigastric vessels
• -lateral border of rectus abdominis
• -inguinal ligament

• 1. Gastrin
• 2. Cholecystokinin (CCK)
• 3. Secretin
• 4. Somatostatin
• 5. Glucse-dependent insulinotropic peptide (GIP)
• 6. Vasoactive intestinal polypeptide (VIP)
• 7. Nitric Oxide
• 8. Motilin

• Source:
• -G cells (antrum of stomach)

• Action:
• -increase gastric H+ secretion
• -increase growth of gastric mucosa
• -increase gastric motility

• Increased by:
• -stomach distention
• -alkalinization
• -amino acids (phenylalalanine and tryptophan)
• -peptides
• -vagal stimulation

• Decreased by:
• -stomach pH <1.5

• Notes:
• -greatly increased in Zollinger-Ellison syndrome
• -increased by chronic PPI use

Mechanism: Increase acid secretion primarily through its effects on ECL cells (leading to histamine release) rather than through direct effect on parietal cells

• Source:
• -I cells (duodenum, jejunum)

• Action:
• -increase pancreatic secretion
• -increase gallbladder contraction
• -decrease gastric emptying
• -increase sphincter of Oddi relaxation

• Increased by:
• -fatty acids
• -amino acids

• Notes:
• -CCK acts on neural muscarinic pathways to cause pancreatic secretion

• Source:
• -S cells (duodenum)

• Action:
• -increase pancreatic HCO3- secretion
• -decrease gastric acid secretion
• -increased bile secretion

• Increased by:
• -acid
• -fatty acids in lumen of duodenum

• Notes:
• -HCO3- neutralizes gastric acid in deuodenum, allowing pancreatic enzymes to function

• Source:
• -D cells (pancreatic islets, GI mucosa)

• Action:
• -decrease gastric acid and pepsinogen secretion
• -decrease pancreatic and small intestine fluid secretion
• -decrease gallbladder contraction
• -decrease insulin and glucagon release

• Increased by:
• -acid

• Decreased by:
• -vagal stimulation

• Notes:
• -inhibitory hormone
• -anti-growth hormone effects (inhibits digestion and absorption of substances needed for growth)

• Source:
• -K cells (duodenum, jejunum)

• Action:
• -Exocrine: decrease gastric H+ secretion
• -Endocrine: increase insulin release

• Increased by:
• -fatty acids
• -amino acids
• -oral glucose

• Notes:
• -oral glucose load used more rapidly than the equivalent given by IV due to GIP secretion

• Source:
• -parasympathetic ganglia in sphincters, gallbladder and small intestine

• Action:
• -increase intestinal water and electrolyte secretion
• -increase relaxation of intestinal smooth muscle and sphincters

• Increased by:
• -distention
• -vagal stimulation

• Decreased by:
• -adrenergic input

• Notes:
• -VIPoma: non-α, non-β islet cell pancreatic tumor that secretes VIP
• -->"WDHA syndrome"
• Watery Diarrhea
• Hypokalemia
• Achlorhydria

• Action:
• -increase smooth muscle relaxation (including LES)

• Notes:
• -lost of NO secretion is implicated in increased lower esophageal tone of achalasia

• Source:
• -small intestine

• Action:
• -produces migrating motor complexes (MMCs: waves of activity that sweep through small intestine in regular waves during states of fasting, help move indigestible substances)

• Increased in:
• -fasting state

• Notes:
• -motilin receptor agonists (erythromycin) used to stimulate intestinal peristalsis

• 1. Intrinsic Factor
• 2. Gastric Acid
• 3. Pepsin
• 4. HCO3-

• Source:
• -parietal cells (stomach)

• Action:
• -vitamin B12 binding protein (required for B12 uptake in terminal ileum)

• Notes:
• -autoimmune destruction of parietal cells --> chronic gastritis and pernicious anemia

• Source:
• -parietal cells (stomach)

• Action:
• -decrease stomach pH

• Increased by:
• -histamine
• -ACh
• -gastrin

• Decreased by:
• -somatostatin
• -GIP
• -prostaglandin
• -secretin

• Notes:
• -Gastrinoma: gastrin secreting tumor that causes continuous high levels of acid secretion and ulcers

• Source:
• -Chief cells (stomach)

• Action:
• -protein digestion

• Increased by:
• -vagal stimulation
• -local acid

• Notes:
• -inactive pepsinogen activated to pepsin by H+

• Source:
• -mucosal cells (stomach, duodenum, salivary glands, pancreas)
• -Brunner's glands (duodenum)

• Action:
• -neutralizes acid

• Increased by:
• -pancreatic and biliary secretion with secretin

• Notes:
• -HCO3- trapped in mucus that covers the gastric epithelium

-secretion from parotid, submandibular and sublingual glands is stimulated by sympathetic and parasympathetic activity

• Amylase: digests starch
• HCO3-: neutralizes bacterial acids
• Mucins: lubricate food

-Normally hypotonic b/c of absorption but more isotonic with higher flow rates (less time for absorption)

-located in glands of fundic mucosa

• Activating Receptors
• 1. M3 (ACh) --> Gq --> Ca --> H+ secretion **ACh from vagus (also activates G cells to produce gastrin)
• 2. CCK_B (Gastrin) --> Gq --> Ca --> H+ secretion
• 3. H2 Receptor (Histamine) --> cAMP --> H+ secretion **Mechanism for ECL cells (activated by gastrin)

• Inhibitory Receptors:
• 1. Prostaglandins: Gi --> inhibits cAMP
• 2. Somatostatin: Gi --> inhibits cAMP

Acid provided by intracellular break down of CO2 and H2O (carbonic anhydrase)

HCO3- transported out of parietal cell by Cl-/HCO3- antitransporter --> alkaline tide

• Medications:
• -Atropine: inhibits M3 receptor
• -H2 blockers: inhibit H2 receptor
• -Misoprostol: activates PG inhibitory pathway
• -PPIs: inhibit H+ ATPase
• **no clinically useful inhibitory of CCK_B receptor

• -located in duodenal submucosa
• -secrete alkaline mucus
• -hypertrophy seen in PUD

• -isotonic fluid
• -low flow --> high Cl
• -high flow --> high HCO3-

• Enzymes:
• 1. α-amylase
• 2. Lipase, phospholipase A, colipase
• 3. Proteases
• 4. Trypsinogen

• Action:
• -starch digestion

• Notes:
• -secreted in active form

• Function:
• -fat digestion

• Pancreatic Lipase:
• -removes FAs from 1 and 3 position
• -requires colipase

• Pancreatic Phospholipase A2 (PLA2)
• -removes FAs from 2 position

• Trypsin
• Chymotrypsin
• Elastase
• Carboxypeptidases

Secreted as zymogens

• Function:
• -protein digestion

-Converted to active enzyme trypsin by enterokinase/enteropeptidase

-Trypsin activates other proenzymes and creates more trypsinogen (positive feedback loop)

-enterkinase/enteropeptidase secreted by duodenal mucosa

• Salivary amylase:
• -starts digestion
• -hydrolyzes α-1,4 linkages to yield disaccharides (maltose + α-limit dextrans)
• 

• Pancreatic Amylase:
• -highest concentration in duodenal lumen
• -hydrolyzes starch to oligosaccharides and disaccharides

• Oligosaccharide Hydrolases:
• -at brush border of intestine
• -rate-limiting step in carbohydrate digestion
• -produce monosaccharides from oligo- and disaccharides

-only monosaccharides can be absorbed by enterocytes (glucose, galactose, fructose)

• SGLT1:
• -uptake of glucose and galactose
• -Na+ dependent

• GLUT5:
• -uptake of fructose by faciliated diffusione

• GLUT2:
• -transports all monosaccharides into the blood

• D-xylose absorption test:
• -distinguishes GI mucosal damage from other causes of malabsorption
• -D-xylose is a simple sugar that doesn't require digestion, only requires intact GI mucosa
• -D-xylose is secreted in the urine

• Iron
• -absorbed as Fe²⁺ in the duodenum

• Folate
• -absorbed in the jejunum

• B12:
• -absorbed in the ileum along with bile acids
• -requires intrinsic factor

-unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum

• M cells:
• -antigen uptake
• 

• B cells:
• -stimulated in germinal centers of Peyer's Patches differentiate into IgA-secreting plasma cells
• -remain in lamina propria
• -IgA receives protective secretory component and is then transported across the epithelium to the gut

"IgA, the Intra-Gut Antibody"

• Composed of:
• -Bile salt (bile acids conjugated to glycine or taurine, makes them water soluble)
• -phospholipids
• -cholesterol
• -bilirubin
• -water
• -ions

Cholesterol --> bile acids catalyzed by cholesterol 7α-hydroxylase (rate limiting)

• Functions:
• 1. Digestion and absorption of lipids and fat-soluble vitamins
• 2. Cholesterol excretion (body's only means of eliminating cholesterol)
• 3. Antimicrobial activity (via membrane disruption)

• -product of heme metabolism (in reticuloendothelial system)
• -removed from blood by liver
• -conjugated to glucuronate (to make it soluble)
• -excreted in bile

• Direct bilirubin:
• -conjugated with glucoronic acid
• -water soluble

• Indirect bilirubin:
• -unconjugated
• -water insoluble

• Heme Metabolism:
• -broken down into iron and protoporphyrin
• -in reticuloendothelial macrophages (into biliverdin then bilirubin)
• -unconjugated bilirubin is released into the plasma where it is bound to albumin
• -uptake into hepatocytes

• Bilirubin Conjugation:
• -conjugated to glucuronic acid by UDP glycuronyl transferase (UGT)
• -excreted in bile into small intestine

• Bilirubin Homeostasis:
• -bacteria in the gut can metabolism bilirubin to urobilinogen
• -80% of urobilinogen is excreted in feces as stercobilin (gives stool its color)
• -20% of urobilinogen is passively reabsorbed through the colonic mucosa
• -90% of reabsorbed urobilinogen goes into the enterohepatic circulation
• -10% of reabsorbed urobilinogen is excrete in the urine as urobilin (characteristic color)