Gastrointestinal Tract Layers

Gastrointestinal Tract Layers

• Mucosa is the innermost layer.
  • Epithelium: A single layer of specialized cells involved in hormone secretion and release.
  • Lamina propria: Connective tissue layer containing glands, hormone-containing cells, lymph nodes, and capillaries.
  • Muscularis mucosa: Thin muscle layer responsible for folding and creating ridges in the mucosal layers.
• Submucosa contains glands, large blood vessels, and lymphatics.
  • Submucosal plexus (Meissner’s plexus) is a nerve net within the submucosa and part of the enteric nervous system, involved in secretory activity.
• Muscularis externa is composed of an inner layer of circular muscle and an outer layer of longitudinal muscle.
  • Myenteric nerve plexus is located between the muscle layers and involved in motor activity.
• Serosa is the outermost layer consisting of connective tissue and a layer of epithelial cells.
  • Autonomic nerve fibers run within the serosa, eventually synapsing on target cells and the enteric nerve plexus.

Nervous Control of the GI Tract

• The enteric nervous system is a vast neural network within the GI tract, which controls normal GI function.
• Innervation of the enteric nervous system is provided by the autonomic nervous systems, serving as the final mediator for neurally mediated changes.
• Sympathetic activity increase slows processes, using Norepinephrine (NE).
• Parasympathetic activity increase promotes digestive and absorptive processes.
  • This involves acetylcholine (ACH), vasoactive intestinal peptide (VIP), and gastric-releasing peptide (GRP), which stimulates gastrin release from G cells.

Characteristics of Smooth Muscle

• Resting membrane potential of smooth muscle cells is -40 to -65mV, close to depolarization.
• Interstitial cells of Cajal generate the oscillation of membrane potential, acting as pacemakers and creating slow waves, also known as basic electrical rhythm, which trigger action potentials when a threshold is reached.
• Action potentials in smooth muscle are generated by opening slow sodium and calcium channels.
• The duodenum contracts most frequently.

Motor Activity in Smooth Muscle

• Stretching smooth muscle induces a contractile response.
• Gap junctions create an electrical syncytium, allowing coordinated contractions.
• Slow waves lead to contractions, and action potentials strengthen these contractions.
• Pacemaker activity initiates intrinsic motor activity.
• Tonic contraction at sphincters functions as valves.

Swallowing

• Swallowing is a reflex controlled by the brain stem, with efferent input via the Vagus nerve.
• Events include:
  • Relaxation of the upper esophageal skeletal muscle sphincter (UES)
  • Primary peristaltic wave
  • Relaxation of lower esophageal smooth muscle sphincter (LES) via VIP, which uses NO to relax the smooth muscle
  • Relaxation of the proximal stomach, also known as receptive relaxation
• A secondary peristaltic wave is initiated by local distension of the esophagus if the primary wave does not succeed, and this process is not "conscious."

Esophageal Disorders

• Achalasia is the failure of the LES to relax, resulting in food retention in the esophagus, caused by enteric nerve abnormalities and weak peristaltic waves.
• Gastroesophageal reflux disease (GERD) occurs if the LES does not maintain tone.
• Diffuse esophageal spasm is a spasm of the esophageal muscle, with characteristics similar to a heart attack.
• Dysphagia is difficulty in swallowing.

Gastric Motility

• Stimulation:
  • Acetylcholine release is triggered by parasympathetic activation.
  • Local distension (dilation)
• Inhibition:
  • Low pH inhibits gastrin release.
  • Feedback from duodenal hormones like CCK, secretin, and GIP.
• Stomach emptying: liquids empty faster than protein, which empties faster than fat.
  • The pylorus regulates stomach emptying.
  • A contraction wave closes the sphincter, moving a small volume into the duodenum.
  • CCK, GIP, and secretin increase pyloric contraction, slowing stomach emptying.

Small Intestinal Motility

• Segmentation contractions are rhythmic contractions in adjacent sections that create mixing movements.
• Peristaltic movements are propulsive, with waves of contraction preceded by muscle relaxation.
  • The ileocecal sphincter between the small and large intestine is normally closed.
  • Ileum distention creates a muscular wave that relaxes the sphincter.
  • Colon distention triggers a nervous reflex that constricts the sphincter.

Colon Motility

• Segmentation contractions create bulges known as haustrations in the colon.
• Mass movements are propulsive and prolonged compared to peristaltic movements in the small intestine.

Migrating Motor Complex (MMC)

• MMC is a propulsive movement during fasting that starts in the stomach and moves undigested material from the stomach to the small intestine and then to the colon.
• During fasting, MMC repeats every 90-120 minutes, and when one movement reaches the distal ileum, a new one starts in the stomach.
• MMC is correlated with high motilin levels, and it removes undigested material and reduces bacterial migration from the colon into the small intestine.

Defecation

• Defecation is a CNS-controlled reflex initiated by a mass movement filling the rectum, leading to internal anal sphincter relaxation and external anal sphincter contraction.
  • Voluntary relaxation of the external sphincter, combined with propulsive contraction of the distal colon leads to the action.
  • Lack of innervation of the external sphincter results in involuntary defecation when the rectum fills.

Salivary Secretions

• Parotid gland secretions are serous (lacking mucin).
• Submandibular and sublingual gland secretions are mixed mucus and serous and are primarily controlled by the parasympathetic system.
• Composition:
  • Low in Na+ and Cl- due to reabsorption.
  • High in K+ and HCO3- with a pH of 8.
  • Low tonicity due to NaCl reabsorption.
  • Alpha-amylase (ptyalin) is secreted in active form to begin carbohydrate digestion.
  • Contains mucus, glycoprotein, immunoglobulins, and lysozymes.

Gastric Secretions

• Epithelial cells covering the gastric mucosa secrete a viscous alkaline fluid of mucin and bicarbonate to protect the stomach lining from HCl.
  • Nonsteroidal anti-inflammatory drugs like aspirin reduce mucin and bicarbonate secretion.
  • The mucosa surface is studded with the openings of the gastric glands.
  • Glands in the upper cardiac and lower pyloric regions secrete primarily mucoidal fluid, while gastric glands can secrete fluid with a pH as low as 1.0.

Main Cells Composing Gastric Glands

• Parietal cells:
  • Secrete HCl.
  • Secrete intrinsic factor, which combines with vitamin B12 and is reabsorbed in the distal ileum
• Chief cells:
  • Secrete pepsinogen, which is converted to pepsin in the presence of acid.
  • Secrete gastric lipase
• Mucous neck cells secrete protective mucus and HCO3.

Pancreatic Secretions

• Food in the stomach stimulates stretch receptors and vasovagal reflexes, resulting in a small secretory volume, and sympathetic inhibition has only a minor influence.
• Major control is via secretin and CCK.
• Pancreatic Enzymes:
  • Trypsin inhibitor prevents protease activation within the pancreas.
  • Ribonucleases and deoxyribonucleases, high in the diet of certain food types.
  • Pancreatic amylases hydrolyze 1,4-glucoside linkages in complex carbohydrates.
  • Pancreatic lipase attaches to and digests lipid droplets.
  • Cholesterol esterase hydrolyzes cholesterol esters, yielding cholesterol and fatty acids.

Control of Pancreatic Secretions

• Secretin, is released when acid enters the duodenum. The release of HCO3- rich fluid neutralizes stomach acid.
• CCK (cholecystokinin) released when partially digested material (fat, amino acids, peptides) enters the duodenum. Release of amylases, lipases, and proteases.
• Bile Salts- actively secreted by the liver, forming micelles for lipid-soluble material transport within the small intestine, vital for digestion, transport, and absorption from the duodenum to the distal ileum.

Bile Pigments

• Bilirubin is a lipid-soluble metabolite of hemoglobin.
• Stercobilin is the product of bilirubin metabolism by intestinal bacteria that gives stool its brown color.

Control of Bile Secretion

• Secretin stimulates fluid secretion into bile canalicular ducts.
• CCK stimulates gallbladder contraction and relaxation of the sphincter of Oddi.

Enterohepatic Circulation

• Bile acids/salts enter the portal vein and travel to the liver, which secretes them into the cystic duct, re-entering the duodenum; this recycling is significant in fat digestion.
• Elevated plasma bilirubin levels result in jaundice; severe accumulation in the brain causes neurological disturbances known as kernicterus.

Small Intestinal Secretions

• Villi surface epithelial cells with microvilli
  • Water and electrolyte reabsorption is highest at the top of the villus.
  • Water and electrolyte secretion is highest at the bottom.

Digestion

• Triglycerides and proteins begin their digestive process in the stomach and continue in the small intestine.
• Carbohydrates begin digestion in the mouth and continue in the small intestine.

Absorption

• Carbohydrates and proteins are absorbed via facilitated transport across the luminal and basal membranes.
• Lipids are diffused to the brush border via micelles and bile salts are actively transported in the distal ileum.
• Celiac disease is an immune response to gluten that damages intestinal cells, decreasing the absorptive capacity of the small intestine.

Electrolytes Absorption

• Duodenum: water-soluble vitamin absorption begins here and continues through the small intestine, which also absorbs iron and calcium.
• Jejunum: absorption of water and electrolytes happens here.
• Ileum: net reabsorption of water, sodium, chloride, and potassium take place. Distal ileum absorbs the reabsorption of bile salts and intrinsic factor with B12.
• Colon: there is net reabsorption of water and sodium chloride, most of the water and electrolytes get absorbed and have mainly a storage function, along with minor absorption of lipid-soluble substances.

Diarrhea Effects

• Net secretion of bicarbonate and potassium results in diarrhea, producing metabolic acidosis and hypokalemia, except in infants, where it can be hypotonic, causing losses of isotonic fluid rich in bicarbonate and potassium.

Respiratory System & PFT

• Pulmonary function test (PFT) consists of 3 individual tests:
  • Measurements of static lung compartments like lung volumes.
  • Airflow, used with a spirometer to evaluate dynamic compliance.
  • Alveolar membrane permeability is tested with carbon monoxide as a marker of diffusion.

Measurements of Lung Volumes and Capacities:

• Tidal volume (Vt): the air entering or leaving the lungs per respiratory cycle (500mL).
• Functional residual capacity (FRC): the amount of gas in the lungs at the end of passive expiration (2700mL), a marker for lung compliance.
• Inspiratory capacity (IC): is the maximum volume of gas inspired from FRC (4000mL).
• Inspiratory reserve volume (IRV): the additional air inhaled after normal inspiration (3500mL).
• Expiratory reserve volume (ERV): the additional volume expired after passive expiration (1500mL).
• Residual volume (RV): the air remaining in the lung after maximal expiration (1200mL).
• Vital capacity (VC): the maximum volume expired after maximal inspiration (5500mL).
• Total lung capacity (TLC): the amount of air in the lung after maximal inspiration (6700mL).

Ventilation

• Total ventilation (TV) or minute ventilation is the total amount of air moved in or out of the lungs per minute.
• Dead space: the air present in the lungs that do not exchange O2 and CO2 with blood.
  • Anatomic dead space: the conducting zone ending at the terminal bronchioles with the amount in mL equal to a person's weight in pounds. (Anatomic dead space of 150mL in a 150 lb individual).
  • Alveolar dead space: the alveoli with air but no blood flow in the surrounding capillaries.
  • Physiologic dead space: the total of dead space in the lung system, alveolar and anatomic dead space.
  • Total ventilation = VT x (f) =500 (15) =7500 mL/min
• Minute ventilation (V): the total amount of air entering the lungs per minute.
• Alveolar ventilation (Va): the amount of room air delivered to the respiratory zone per breath.
  • The first 150 mL of each inspiration does not contribute to alveolar ventilation as it remains in the anatomic dead space.
  • Va = (VT-VD) f = (500mL-150mL) 15 = 5250 mL/min
• Alveolar volume inspiration is 350mL.

Lung Mechanics

• Inspiration contraction of the diaphragm increases the vertical axis of the chest. Contraction of the external intercostal muscles causes the ribs to rise, increasing the anterior-posterior dimensions of the chest.
• Expiration is normally passive under resting conditions due to the relaxation of inspiratory muscles and elastic recoil. For forced expiration, the internal intercostals and muscles of the abdominal wall contract, compressing the chest wall and forcing the diaphragm upwards, including external oblique, rectus abdominis, external oblique and transverse adbominus muscles.

Ventilation

• Inspiration: Increased, negative intrapleural pressure leads to an increased pressure gradient across the vasculature which causes the expansion of the great veins and right atrium, decreasing intravascular pressure while increasing the pressure gradient to the right heart.
  • Systemic venous return and right ventricular output increase -Venous return to the left heart and output of the left ventricle decreases, reducing systemic arterial pressure.
• Expiration: More positive Intrapleural pressure decreases VR pressure gradient
• Systemic venous return and output of the right ventricle are decreased.
• Pulmonary vessels compress reducing blood volume in pulmonary circuit
• Increase in blood volume and output of left ventricle increases arterial pressure

Pneumothorax

• Traumatic (chest wall perforation) and spontaneous (ruptured alveolus).
  • Simple pneumothorax leads to an increase in intrapleural pressure from -5cm H2O to atmospheric pressure.
  • With pneumothorax lung recoil decreases to zero which causes lung collapse.
  • Transpulmonary pressure becomes negative as a result.
• Tension develops if opening of lung to the pleural space allows entry but prevents exit.
  • Results in positive intrathecal pressure.
  • Strong Inspiratory efforts promote the entry of air into the pleural space, but during expiration, the valve closes, and positive pressures are created in the chest cavity.
  • Ventilation decreases but positive pressures also decrease venous return and cardiac output.
  • It develops in patients on positive-pressure ventilators.

Tension Pneumothorax

• Common signs
  • Respiratory distress
  • Asymmetry of breath sounds
  • Deviation of trachea to the side opposite pneumothorax -Markedly depressed cardiac output

Respiratory Distress Syndrome (RDS)

• Infant, or hyaline membrane disease, caused by a surfactant deficiency.
• Adult - acute lung injury from infection:
  • Injury resulting in capillary endothelial damage and interstitial edema that increases flow that increases alveolar permeability and resulting edema.

Alveolar-Blood Gas Exchange

Normal Lung

• Partial Pressure of a Gas in Ambient Air Dalton’s law - the total pressure exerted by a gas mixture is the sum of the pressures exerted independently by each gas in the mixture, represented by: Pgas = Fgas (concentration of gas) x Patm (atmospheric pressure) By convention gas partial pressure is expressed in terms of its dry gas concentration. For air PO2 = 0.21x760 = 160 mmHg
• Inspired air (at 37* C)is warmed and humidified but is not engaged in gas exchange. It is the fresh air in the anatVD that is about to enter the respiratory zone.

Partial Pressure

• PH2O is temperature dependent. At 37* C, PH2O is 47 mmHg
• Humidifying air reduces partial pressure of all other gases present.
• Plgas(partial pressure of inspired gas) = Fgas (Patm-PH2O), Ex. PO2 of inspired air = 0.21(760-47) = 150mmHg
• Normal PO2 and PCO2 are same in alveolar compartment and pulmonary end capillary blood.

Alveolar Ventilation

• Inverse relationship between PACO2 and alveolar ventilation.
• Elevated alveolar ventilation leads to hyperventilation which depresses PACO2
• Depressed alveolar ventilation leads to Hypoventilation which elevates PACO2

Metabolic Rate

• A direct correlation between alveolar PCO2 and body metabolism where changes in body metabolism has equivalent changes in ventilation that keeps PACO2 constant.
  • Decrease in body temp without the change in ventilation decreases PaCO2 resulting hyperventilation.

Factors That Affect Alveolar O2

• Increase in atmospheric pressure (hyperbaric chamber) increases alveolar PO2, and high altitude decreases alveolar PO2 - Increase in inspired oxygen concentration increases alveolar PO2 - Increase in alveolar PCO2 decreases alveolar PO2, and decrease in alveolar PCO2 increases alveolar PO2.

Neural Regulation of Alveolar Ventilation

• Occurs thru chemoreceptors input to the central nervous system. Stronger this stimulation is the greater is alveolar ventilation.
• Two groups of receptors help control ventilation:
  • Central Chemoreceptors: in CNS near the medulla surface that when stimulated, increases ventilation. These directly monitor and get stimulated by cerebrospinal fluid (H+) and CO2, which is possible because the blood-brain barrier freely allows CO2 to pass so the receptors can change with PCO2 arterial change in systemic. Very sensitive and the main driver of ventilation during normal resting conditions at sea.
    • Main drive for ventilation is CO2 (H+) on the central chemoreceptors.

Peripheral Chemoreceptors

• Are within bodies at 2 locations that are bathed in arterial blood. -Near carotid sinus that provide afferents to CNS in nerve IX(glossopharyngeal ) -Near aortic arch that has afferents to CNS in nerve X(vagus).
• Bodies contain 2 receptors:
  • H+/CO2 receptors less sensitive than central chemoreceptors but still contribute to ventilation. Under normal resting sea conditions drive for ventilation is CO2.
  • PO2 receptors monitor content of PO2 and not oxygen.
• They respond to PO2 and monitor dissolved oxygen not oxygen on Hg, however if systemic arterial PO2 is ~100mmHg or above normal, there is little receptors stimulation
• Only stimulated by a remarkable decline in systemic arterial PO2.
• Adaptations increases to hypoxia with CO2 retention but these receptors do not adapt.

Clinical Correlate

• In anemia, oxygen is reduced, PaO2 is normal. It does not stimulate ventilation however, deficiency is caused by lactic acid build up with stimulates periphreal receptors.

Central Respiratory Centers

• inherent rhythm for respiration - location
  • Inspiratory Center
  • Expiratory Center Spontaneous breathing only only occurs when an intact Medulla is connected to the diaphragm,(phrenic nerve).

Abnormal Breathing

• Apneustic: In prolonged inspirations this alternating with short expirations- Vagul balance in the medulla Ponds is disrupted from lesions.
• Cheyne-Stokes: cycles of higher rates with lower rates with mid brain damage/CHF

Respiratory Stress - Environmental

High Altitude: Pressure reduced due to altitude. Therefore, PAO2/PaO2 is <100, Low arterial stimulates peripheral receptors and increases alveolar ventilation. At altitude ventilation changes from a sea pressure stimulus to PO2 stimulus and hyperventilation results. Hypoxia: Can result, Circulating levels of erythropoietin and higher red cell concentration because erythropoietin = more red blood.

High Pressure Environment

• 21% O2 & 79% N2 when breathed is hyperbaric. 02 and N2 will increase in systemic and arterial blood, nitrogen will also increase in body compartments.

Oxygen

• Oxygen - Oxygen toxicity created by free oxygen
• Clinical uses include - Poisoning-Monoxide, Grafts and gangrene.

Nitrogen

• Feeling euphoria at higher levels
• Bends: Caused by pressure from environment - rapid pressure after higher exposures that can result in joints or bloodstream, or air to emboli in the vasculature.