Human Digestion and Metabolic Regulation

The Human Digestive System: An Introduction

The digestive system transfers organic nutrients, vitamins, minerals, and water from the foods we eat to the internal environment. Upon entering the body, food moves through the gastrointestinal (GI) tract, and the nutrients are absorbed and transported to the circulatory system where they are utilized.

Net Gain to the Body

Food and air are the primary sources of net gain to the body.

Distribution within the Body

Nutrients and substances are distributed throughout the body via the GI tract, lungs, storage deposits, and metabolism.

Net Loss from the Body

Excretion from the body occurs via the lungs, GI tract, kidneys, and skin.

Epithelial Cells

Epithelial cells separate compartments and are crucial in the digestive system.

The Human Body's Composition

The human body is composed of macromolecules (carbohydrates, lipids, proteins), vitamins, minerals, and water.

Gastrointestinal Tract Structures

Main GI Tract Pathway

• Mouth
• Pharynx
• Esophagus
• Stomach
• Small Intestine
• Large Intestine
• Anal Canal

Accessory Organs of Digestion

These organs add secretions to the GI tract to aid digestion:

• Salivary Glands
• Liver
• Gallbladder
• Pancreas

Digestive System Processes

There are four primary processes in the digestive system:

1. Digestion
2. Absorption
3. Motility
4. Elimination

Digestion

Digestion is the breakdown of whole food into absorbable pieces.

Mechanical Digestion

Physical breakdown of food.

Chemical Digestion

Enzyme-mediated breakdown of food.

Absorption

Digested molecules move from the lumen of the GI tract to epithelial cells and then to the blood or lymph vessels.

Blood Absorption

Carbohydrates (CHO), amino acids, and minerals are absorbed into the blood.

Lymph Absorption

Fats and fat-soluble vitamins are absorbed into the lymph.

Secretion

Enzymes and other chemicals are released by exocrine glands to aid in digestion.

• Salivary Glands: Saliva enzymes
• Stomach: Digestive enzymes
• Liver: Bile
• Pancreas: Digestive enzymes

Motility

Motility refers to the contractions of smooth muscle in the GI tract.

Motility Functions

Motility functions include mixing contents to aid in digestion and absorption, and moving contents through the GI tract from mouth to anus.

Structure of the GI Tract Wall

The GI tract wall consists of four main layers:

1. Mucosa Layer:
   • Epithelium: Absorptive cells, exocrine cells, endocrine cells
   • Muscularis Mucosae
2. Submucosa
3. Muscularis Externa
4. Serosa

Nervous System Innervation

The GI tract is innervated by three main components:

1. Submucosal Plexus
2. Myenteric Plexus
3. Autonomic Nervous System (ANS)

Intestinal Epithelium

Specialized intestinal epithelial structures include:

• Absorptive Cells: Primary cells for nutrient uptake.
• Circular Folds: Walls fold into finger-like projections known as villi.
• Microvilli: Individual intestinal cells make up the villi, significantly increasing the surface area for absorption and secreting digestive enzymes.

Blood & Lymph Vessels

Nutrient transport pathways include:

• Mucosal and Submucosal layers
• Microvilli
• Lacteals (for lymph absorption)
• Intestinal Capillaries (for blood absorption)

The Digestive Process: A Journey Through the Body

1. Mouth: Mechanical digestion begins, saliva is added, resulting in a bolus.
2. Pharynx & Esophagus: Transport the bolus to the stomach.
3. Stomach: Stores and partially digests macromolecules, produces gastric secretions, and regulates the entry of chyme into the small intestine.
4. Small Intestine: The primary location for the majority of nutrient absorption. It receives secretions from the liver and pancreas to aid digestion.
5. Large Intestine: Responsible for fine-tuning water and ion absorption and hosts a high concentration of bacterial colonies.

Regulation of Digestion

Luminal Stimuli

Stimuli within the lumen cause reflexes, such as the distension of the GI tract wall (indicating how much food has been consumed).

Effectors

The muscle layers in the GI tract wall act as effectors.

Enteric Nervous System (ENS)

The ENS is the local control system for the GI tract, often referred to as the "brain of the gut."

Neural Regulation

Involves short and fast reflexes, including feedforward control.

Hormonal Regulation

Enteroendocrine cells release hormones into the bloodstream to impact GI function.

Effects of GI Hormone Regulation

Four key hormones regulate GI function:

1. Gastrin
2. Cholecystokinin (CCK)
3. Secretin
4. Gastric Inhibitory Peptide (GIP)

Gastrin

Released by endocrine cells in the stomach.

Stimuli for Gastrin Release

• Stomach distension
• Peptides and amino acids in the stomach
• Increased parasympathetic nervous system (PNS) activity

Effects of Gastrin

• Increases gastric secretion
• Increases gastric motility
• Increases colonic motility

CCK & Secretin

Released by endocrine cells in the small intestine.

Stimuli for CCK & Secretin Release

• Amino acids
• Fatty acids
• Hydrogen ions (H+)

Effects of CCK & Secretin

• Increase bicarbonate (HCO3-) and pancreatic enzyme secretion
• Increase bile discharge
• Decrease gastric acid production

GIP (Gastric Inhibitory Peptide)

Secreted by epithelial cells in the small intestine, acting as a feedforward mechanism.

Stimuli for GIP Secretion

• Carbohydrates (CHO) in the small intestine
• Fats in the small intestine

Effects of GIP

• Pancreas: Increases insulin secretion
• Increases lipoprotein lipase secretion

Detailed Organ Functions in Digestion

Mouth

Digestion starts in the mouth with both mechanical and chemical digestion.

Saliva

Saliva contains:

• Water
• Mucus
• Bicarbonate (HCO3-)
• Lysozyme
• Amylase (an enzyme class that begins the digestion of carbohydrates)
• Lipase (begins the digestion of fats)

Lower Esophageal Sphincter

This sphincter acts as a barrier between the stomach and esophagus.

Stomach

The stomach mixes the bolus with gastric secretions to form chyme.

Gastric Emptying Rate

Regulates the rate at which chyme empties into the small intestine.

Anatomy of the Stomach

• Lower Esophageal Sphincter
• Body
• Antrum
• Pyloric Sphincter
• Duodenum of the Small Intestine (where chyme enters)

Stomach Secretions

The stomach secretes several substances that aid digestion:

1. Mucus Cells: Line and protect the stomach.
2. Parietal Cells: Secrete hydrochloric acid (HCl) and intrinsic factor.
3. Chief Cells: Secrete pepsinogen.

Hydrochloric Acid (HCl)

Denatures proteins and kills most bacteria.

Stimuli Controlling HCl Secretion

Two main stimuli control HCl secretion:

1. Gastrin: Increases with stomach distension and the presence of amino acids in the stomach.
2. Acetylcholine: Increases with parasympathetic nervous system activity, such as the sight and smell of food.

Pepsin

Pepsin accelerates protein digestion. Pepsinogen, a zymogen (inactive enzyme precursor), is secreted by chief cells and activated by low pH, paralleling HCl secretion.

Pepsin Function

Accelerates protein digestion.

Gastric Motility

A resting stomach is not very large, but during relaxation, it can accommodate large amounts of food via parasympathetic activity through smooth muscle.

Gastric Motility (Peristalsis)

Peristaltic waves sweep over the stomach, becoming stronger in the antrum. This action closes the pyloric sphincter, causing retropulsion, which further aids chemical digestion.

Gastric Motility (Regulation)

Gastric motility is the first control point in regulating the timing of digestion and is a primary factor influencing when substances appear in the bloodstream.

Small Intestine Overview

The small intestine is the primary site for digestion and absorption. It has three segments:

1. Duodenum
2. Jejunum
3. Ileum

Intestinal Mucosa and Submucosa Features

Key features include:

• Circular Folds
• Villi
• Microvilli
• Goblet Cells (responsible for mucus secretion)

Accessory Organs Contributing to the Small Intestine

These organs contribute to the GI tract to enhance digestion and protect the mucosa:

• Liver
• Gallbladder
• Pancreas
• Associated Ducts (e.g., bile duct, pancreatic duct)

Liver

The liver performs various metabolic functions and has a digestive exocrine function: bile production and secretion.

Bile

Bile is formed in the liver and stored in the gallbladder. During a meal, bile is ejected from the gallbladder into the duodenum. This stimulates the release of fatty acids and amino acids, which in turn cause CCK secretion.

Pancreas

The pancreas performs both endocrine and exocrine functions. Its exocrine function includes secreting digestive enzymes:

• Pancreatic Amylase: Digests carbohydrates (CHO)
• Pancreatic Lipase: Digests fats
• Trypsin: Digests proteins
• Bicarbonate: Neutralizes stomach acid

Macronutrient Digestion & Absorption

Carbohydrates

Carbohydrate digestion starts in the mouth and is completed in the small intestine.

• Polysaccharides: Broken down by amylase into disaccharides.
• Disaccharides: Broken down by sucrase and lactase into monosaccharides.

Carbohydrate absorption across the luminal membrane occurs via glucose, galactose, and fructose. GLUT transporters facilitate movement across the basolateral membrane into the bloodstream.

Protein Digestion

Protein digestion starts in the stomach and ends in the small intestine.

• Proteins: Broken down by pepsin (in stomach) and trypsin (in small intestine).

Absorption across the luminal membrane occurs via secondary active transport for small peptides and amino acids. Movement across the basolateral membrane is primarily by facilitated diffusion.

Hepatic Portal System

The hepatic portal vein transports absorbed nutrients from the small intestine to the liver, where the nutrients are processed before entering general circulation.

Fats

Bile emulsifies fats, breaking them into smaller droplets.

• Emulsion Droplets: Formed by bile salts.
• Micelles: Smaller structures formed from emulsion droplets, containing free fatty acids (FFA) and monoglycerides.
• Chylomicrons: Re-esterified triglycerides packaged into chylomicrons for transport into the lymphatic system.

Vitamins, Minerals, and Water Absorption

Vitamins and Minerals

Vitamins and minerals undergo little digestion within the GI tract and are absorbed primarily from the small intestine.

• Fat-soluble Vitamins (A, D, E, K): Absorbed via the same pathway used for fat absorption.
• Water-soluble Vitamins (B and C): Absorbed from the small intestine.
• Vitamin B12: Requires intrinsic factor for absorption.
• Minerals: Also absorbed in the small intestine.

Water

Water is absorbed through osmosis, primarily in the small intestine.

Large Intestine Overview

The ileum empties into the large intestine, which consists of the colon and rectum. The large intestine lacks circular folds and villi.

Large Intestine Function

• Stores undigested food prior to elimination.
• Continues water and salt absorption.
• Hosts gut microbiota.

Large Intestine Motility

Large intestine motility is the rate-limiting step for total gut transit time.

Gut Transit Time (Approximate)

• Mouth/Esophagus: 0 hours
• Stomach: 1-5 hours
• Small Intestine: 2-4 hours
• Large Intestine: 5-70 hours
• Rectum: 0 hours
• Total: 8-80 hours

Metabolic States

Absorptive State

Occurs 0-4 hours after eating, maximizing energy storage. Nutrients enter the bloodstream from the GI tract.

Glucose Fate #1: Cellular Energy Production

Glucose is used for energy by the body and tissues.

Glucose Fate #2: Glycogenesis

Glycogenesis is the process of converting glucose into glycogen, storing glucose within the body.

Glucose Fate #3: Triglyceride Synthesis

Leftover glucose not used in glycogenesis is converted to glycerol and fatty acids to form triglycerides.

Lipid Fates

• Triglycerides: Absorbed lipids are rebuilt into triglycerides in adipose tissue.
• Sources of Plasma Cholesterol: Cholesterol can be ingested or synthesized within the body. Plasma cholesterol is carried in various lipoproteins (Chylomicrons, VLDL, IDL, HDL).

Amino Acid Fates

• Amino Acid Fate #1: Converted to Proteins: Absorbed amino acids are converted into proteins in various tissues.
• Amino Acid Fate #2: Ketoacids: Excess amino acids are deaminated in the liver and converted into ketoacids. Urea is produced during this process. Ketoacids are carbohydrate-like intermediates used for energy; if not used for energy, they can be converted to fatty acids and stored as fat.

Regulation of Events in the Absorptive State

Insulin dominates metabolism during the absorptive state. Insulin is secreted by beta cells from the pancreas. It acts on skeletal muscle, adipose cells, and the liver to facilitate the previously mentioned events.

Insulin Mechanism of Action: Receptors

Insulin is a polar molecule, and its receptor is located on the outside of the cell membrane.

Insulin Mechanism of Action: Glucose Uptake

Insulin increases the insertion of GLUT4 transporters into the cell membrane of muscle and adipose tissue, facilitating glucose uptake.

Insulin Mechanism of Action: Enzymes

Insulin increases the activity of enzymes controlling the synthesis of glycogen, proteins, and fats. Insulin also decreases the breakdown of macromolecules and increases the activity of glycolysis.

Stimuli for Insulin Release: Blood Glucose

The major stimulus for insulin secretion is an increase in blood glucose concentration. The body detects changes in blood glucose, effectors are activated to regulate it, and the net effect is increased glucose uptake and storage.

Stimuli for Insulin Release: Other Factors

Insulin secretion can also be influenced by plasma amino acid levels, incretins, sympathetic nervous system (SNS) activity, and parasympathetic nervous system (PNS) activity.

Post-Absorptive State

In the post-absorptive state, the GI tract is empty, and energy must be supplied from the body's stored nutrients.

Euglycemia

Normal blood glucose levels.

Overview of Maintaining Euglycemia

The brain requires a constant supply of glucose (normal range: 55-99 mg/dL).

Sources of Blood Glucose: Glycogenolysis

The liver can add glucose to the blood via glycogenolysis (breakdown of glycogen).

Sources of Blood Glucose: Gluconeogenesis

The liver and kidneys can synthesize new glucose via gluconeogenesis from:

• Lactate (from muscle)
• Glycerol (from triglyceride breakdown)
• Amino acids (from protein breakdown)

Glucose Sparing

To spare glucose for the nervous system, glycolysis is decreased, and most of the body's energy comes from:

1. Fatty acids from adipose tissue lipolysis.
2. Ketone bodies produced from fatty acids in the liver.

Post-Absorptive State: Insulin's Role

The major factor leading to the events of the post-absorptive state is the decrease in plasma insulin caused by the decrease in blood glucose.

Glucagon Actions

Glucagon acts on the liver, stimulating:

1. Glycogenolysis
2. Gluconeogenesis
3. Ketone synthesis

The net effect is an increase in plasma glucose and ketone bodies that the body can use as fuel.

Stimuli for Glucagon Secretion

The primary stimulus for glucagon secretion is a decrease in plasma glucose.

Glucose Counter-Regulatory Systems: Cortisol

Cortisol has permissive effects on glucagon and epinephrine and can help block the effects of insulin.

Diabetes Mellitus

Diabetes Type 1 (T1DM)

Caused by insulin deficiency arising from the autoimmune destruction of pancreatic beta-cells, resulting in no insulin production.

Diabetes Type 2 (T2DM)

Characterized by insulin resistance, often associated with obesity.