Lower Digestive System

Pancreas → anatomy and function

• Retroperitoneal

• Head, body, and tail

• Endocrine and exocrine function

  • Endocrine: release of insulin, glucagon, and somatostatin into blood stream

  • Exocrine: release of pancreatic juice (alkaline mixture - digestive enzymes, waters, buffers, ions) into duodenum via pancreatic duct

Histology of the pancreas → for endocrine and exocrine

• Endocrine: Islets of Langerhans (pancreatic islet): subtypes of endocrine cells

  • Alpha: glucagon, 18-20% of cells

  • Beta: insulin, 73-75% cells

  • Delta: somatostatin (GHIH), 4-6% of cells

    • D cells also make somatostatin

    • Inhibit release of glucagon and insulin and slows rate of digestion

• Exocrine:

  • Pancreatic acini: pockets of simple cuboidal cells that produce pancreatic juice

    • Empty into series of epithelial lined ducts leading to pancreatic duct

Insulin and glucagon maintain…

• Glucose homeostasis and have antagonistic effects

Beta cells respond to…

• INCREASED blood glucose (hyperglycemia) to release insulin

• Other influences: SNS decreases release, PNS increases release

What is insulin

• Circulates in what form

• Half life

• Degraded by

• Peptide hormone (cannot go through plasma membrane)

• Circulates in free form; half life 3-8 minutes, degraded by liver and kidney

Receptor activity of insulin

• Where are there insulin receptors and what are the exceptions

• Structure

• Steps involved

• Most cells of the body contain insulin receptors (exceptions: portions of brain, kidney, RBC, lining of GI)

  • Tetramer with kinase activity on Beta subunits

    • Beta subunits phosphorylate each other

  • Increase absorption of glucose into cells

  • Promote energy storage

    • In glycogen - liver and skeletal muscle

• Essentially, putting glucose transporters on cell membrane (GLUT4)

• Receptor for insulin is tyrosine kinase

• When insulin binds to alpha subunits → phosphorylates Beta subunits

Overall effect of insulin on target organs

• ANABOLIC

• Stimulates glucose uptake by target cells, and promote synthesis of carbohydrates, fats, and proteins

What is diabetes Mellitus

• Impaired entry glucose into cells and elevation of glucose in blood

• Type I and II

Type I DM

• Around 5% of cases of DM

• Beta cell destruction, due to autoimmune dysfunction

Type II DM

• Around 95% of cases of DM (growing)

• Associated with obesity

• Loss of regulation of:

  • Insulin secretion: beta cells can still make insulin but dysfunctional response to glucose levels

  • Insulin resistance: decreased tissue responsiveness to insulin

Clinical features of DM

• Hyperglycemia

• Glycosuria

• Thirst/urination

• Muscle fatigue

• Bruising

• Nerve tingling/numbness

• Confusion/dizziness

• Cardiovascular disease

• Kidney disease

• Loss of vision

• Diabetic ketoacidosis

  • Excess production of ketone bodies → acid-base imbalance

  • Life threatening if untreated

Pancreatic juice → primary effects and how much

• Neutralize acidic chyme (aqueous component → buffer acidic chyme)

• Enzymatic digestion → vast majority of chemical digestion from enzymes from pancreas

• Pancreatic secretions: approximately 1 liter/day

Aqueous component

• H2O, HCO3- (bicarb), PO4- (phosphate buffering system)

Enzymatic components

• Pancreatic alpha amylase → amylase also in saliva

  • Breaks down carbs

• Pancreatic lipase

  • Breakdown of lipids

• Nucleases

  • Breakdown of nucleic acids

• Pancreatic proteases and peptidases

  • Breakdown of proteins

  • Released in an inactive form; activated when then come in contact with brush border enzymes

Hormonal regulation of pancreatic juice - aqueous component

• Secretin → responsive to pH change

  • Stimulus for release of secretin: decrease pH of duodenal content because we need to buffer chyme

Hormonal regulation of pancreatic juice - enzymatic component

• Cholecystokinin (CCK)

  • Stimulus for release of CCK: breakdown products of fats and proteins in duodenum

  • Additional functions: contraction of gall bladder and relaxation of sphincters

Both of these hormones (secretin and CCK) are released from…

• Enteroendocrine cells in the duodenal mucosa

Function of the liver

• More than 200 functions

• Metabolic regulation

• Hematological regulation

• Production of bile

Metabolic regulation → Liver function

• Extract nutrients from GI system blood before it returns to systemic circulation. Stores nutrients and corrects deficiencies

  • Maintains homeostasis of blood carbohydrate, lipid, and amino acid levels [glycogen storage]

  • Removal of wastes, ie. drugs/toxins to be degraded and conversion of ammonia into urea

  • Storage of vitamins and minerals

Hematological regulation → Liver function

• Immune: macrophages destroy old RBCs cells and antigen presentation

• Synthesis of clotting factors

• Synthesis of plasma proteins

• Synthesis of angiontensinogen

• Removal of hormones

Liver anatomy

• Approximately 3.3 lbs, Reddish brown, located mostly in right upper abdominal cavity

• 4 lobes of liver: Right lobe, left lobe, caudate lobe, quadrate lobe

• Porta hepatis: blood delivered to liver via hepatic portal vein (venous blood from stomach and intestines) and from hepatic artery

Liver histology

• Lobule: functional unit of the liver, hepatocytes arranged in plates around a central vein. Sinusoids allow hepatocytes to ‘filter’ fluid as it moves towards central vein

• Portal triads: found at each corner; branch of hepatic artery, portal vein, bile duct

  • Blood from portal vein and hepatic artery (bringing oxygenated blood to liver) enter hepatic sinusoids which ultimately empty into central hepatic veins (drains into inferior vena cava)

• Hepatocytes synthesize bile which is emptied into small ductules which converge into small bile ducts (carried opposite direction from central vein)

Where is bile produced and then stored/concentrated

• It is produced in the liver; stored and concentrated in the gallbladder

Function of bile

• Break apart large lipid droplets within chyme of the duodenum

Composition of bile

• Bile salts: synthesized from cholesterol

  • Amphipathic: solubilize lipids in an aqueous environment

• Bile pigments: bilirubin (yellow); byproduct of heme degradation

• Ions: buffer the acidity of chyme

• Water: bulk of bile; dilute chyme

How much bile formed and what happens to it

• Around 1 Liter of bile formed/day

• Most of the bile salts are “recycled”

• Bile salts are absorbed in the ileum and returned to the liver via the hepatic portal vein

What does the bile duct system consist of

• All bile produced by hepatocytes ultimately drains into the common hepatic duct

• Bile enters/exits gallbladder via the cystic duct

• Cystic duct and hepatic duct converge to form the common bile duct

Gallbladder

• Hollow pear shaped organ; storage of bile, concentrating of bile (via fluid reabsorption)

Parts of bile duct system

• Hepatopancreatic ampulla: Site of convergence of bile duct and pancreatic duct

• Hepatopancreatic (Oddi) Sphincter: allows bile and pancreatic juice into duodenum

• CCK: hormone, contracts gall bladder, relaxes hepatopancreatic sphincter

Function of the small intestine

• Majority of chemical digestion:

  • Enzymes secreted from small intestinal epithelium (small fraction of digestion)

  • Pancreatic juice

  • Bile from the gallbladder

• Absorption of breakdown products of carbohydrates, lipids, proteins

  • Also vitamins and minerals (90% of nutrient absorption)

• Absorption of fluids:

  • Secretions from accessory glands and GI organs

  • Fluids from food

• Recycling of bile salts

Anatomy of the small intestine

• Duodenum:

  • 10 inch section following stomach; mixing bowl - entry of pancreatic and bile duct - duodenal glands (mucus and bicarbonate); few plicae, small villi

• Jejunum:

  • 8 ft segment following duodenum; majority of chemical digestion and absorption; abundant plicae and large villi

• Ileum:

  • 11.5 ft final segment; remainder of absorption (vit. B12, bile salts); reduction in plicae and villi; abundant lymph tissue; ends at ileocecal valve

Histology of small intestine - what is used to maximize surface are

• Plicae circulars: series of (permanent) transverse folds

• Villi: finger like projections covering entire surface, each villi covered in simple columnar epithelium

• Microvilli (brush border): hair like projections off each epithelial cell

Each villus absorbs productions of digestion into…(small intestine histology)

• Lamina propria: connective tissue

  • Capillaries: carry absorbed material to hepatic portal

  • Central lacteal: lymphatic vessel (transport large materials)

Cell types of small intestine

• Simple columnar epithelium (brush border)

• Goblet cell: produce mucus

• Intestinal crypts (glands) found at the base of the villi

  • Brush boarder stem cells

  • Paneth cells: immune cells; release antibacterial chemicals

  • Endocrine cells: release CCK, secretin, and others

Motility of small intestine

• Duodenum moves chyme toward jejunum

  • ENS: weak peristaltic contractions, regulated by pacesetter cells

• Gastroenteric and gastroileal reflexes: generate majority of peristalsis in remaining intestine

  • Stimulated by stretch in stomach

  • Gastroenteric: increases movement and secretion across entire small intestine

  • Gastroileal: relaxation of the ileocecal valve

• PNS

  • Increase speed and force of ENS

• Intestinal hormones (CCK, motilin)

  • Can enhance or suppress reflexes

Function of the large intestine

• Absorption of fluid and ions:

  • Around 1500 mL chyme/day enters (mostly water) only 200 mL/day exits

  • Efficient absorption of remaining bile salts

• Bacterial synthesis of vitamins: Notably Vitamin K, Biotin (B7), and vitamin B5

  • Then absorbed by large intestine

• Storage and elimination of feces

Composition of feces

• 75% water

• 4% bacteria

• Indigestible materials

• Dead epithelial cells

• Pigments: urobilins and stercobilins (breakdown of heme)

• Nitrogenous wastes: e.g. ammonia (bacterial break down of amino acids)

• Other bacterial metabolites: e.g. hydrogen sulfide

Anatomy of the large intestine

• Divided into three parts (around 5 ft long):

  • Cecum: small pouch, begins compaction

    • Appendix: lymphatic organ

  • Colon: haustra, series of pouches

    • Ascending, transverse, descending, sigmoid segments

  • Rectum: terminal portion

    • Leads to anal canal and anus (opening)

Histology of the large intestine

• Surface of the colon:

  • Smooth: no plicae, no villi

  • Simple columnar epithelium (non micro villiated)

  • Deep intestinal glands (crypts)

    • Numerous goblet cells: mucus

• Arranged into haustra (sacs)

• Muscle layer reduced to think bands called taenia coli

Motility of the large intestine

• Gastroileal reflex: opening of ileocecal valve in response to gastric stretch, moves chyme into cecum

• Movement from cecum to transverse colon:

  • Very slow, hours to allow for water reabsorption

  • ENS

    • Peristaltic waves

    • Segmentation contractions: haustral churning

• Mass movements:

  • Powerful peristaltic contractions

  • Move material from transverse colon through rest of large intestine

  • Stimulated by dissension of stomach and duodenum

  • Occur around 1-3 times a day

Defecation reflex

• Mass movement: push feces into rectum → stimulate stretch receptors

  • Activates ENS defection response:

    • Increased peristalsis in sigmoid colon and rectum

  • Activates PNS defecation response:

    • Increased mass movement in descending and sigmoidal colon

    • Relaxation of internal anal sphincter

• Relaxation of external sphincter: voluntary