Digestive System Overview

Gastrointestinal Pathophysiology

• The GI tract has 4 layers: serosa (outermost), muscularis (longitudinal and circular layers with myenteric and submucosal plexus), submucosa, and mucosa (innermost).
• The enteric plexus is made up of the myenteric and submucosal plexus. The submucosal plexus is also called Meissner's plexus, and the myenteric plexus is also called Auerbach's plexus.
• Peyer's patches in the mucosa are key players in immune surveillance for the GI tract.
• The small intestine has 3 layers (duodenum, jejunum, ileum).
• Duodenum has a tall layer of mucosa, many villi to increase surface area for nutrient absorption, and does the most nutrient absorption.
• Jejunum has tall villi but less than in duodenum.
• Ileum has short, tightly packed villi.
• Stomach has 3 muscle layers (longitudinal, circular, oblique).
• The LES (lower esophageal sphincter) prevents gastric contents from refluxing into the esophagus.
• The pyloric sphincter prevents movement of food into the duodenum until it's churned and mixed with stomach acid.
• Stomach lining includes gastric pits with gastric glands containing different cell types (mucous neck cells, chief cells, parietal cells, G cells, and endocrine cells).
• Chief cells produce pepsinogen, which is cleaved into pepsin, an enzyme that breaks down proteins.
• Parietal cells produce hydrochloric acid and intrinsic factor.
• G cells produce gastrin, which stimulates acid secretion and contraction of the intestines.
• Endocrine cells produce somatostatin and histamine.
• Oxygenated blood circulates to GI organs via branches of the abdominal aorta (hepatic artery to liver, celiac artery to stomach, spleen, and pancreas, superior mesenteric artery to pancreas, small intestine, proximal colon, inferior mesenteric artery to distal colon, rectum).
• Deoxygenated blood drains into the portal vein, processed by the liver, and then carried to the inferior vena cava. The liver is the major glycogen storage organ.

Stomach Lining

• Gastric pits are small depressions in the epithelial lining of the stomach.
• Each pit has a gastric gland at the bottom, which contains different cell types.

GI Tract Circulation

• Oxygenated blood circulates to the GI organs from the abdominal aorta.
• Hepatic artery supplies blood to the liver,
• Celiac artery supplies blood to the stomach, spleen, and pancreas.
• Superior mesenteric artery supplies blood to the pancreas, small intestine, and proximal colon.
• Inferior mesenteric artery supplies blood to the distal colon and rectum.
• Deoxygenated blood from all GI organs drains into the portal vein.

Process of Acid Secretion

• Gastric acid secretion is stimulated by vagal nerve stimulation (acetylcholine), gastrin (from G cells), and histamine.
• H2 antihistamines inhibit gastric acid secretion.
• The rate of gastric acid secretion is different when fasting versus eating.
• Fasting: very little acid secretion, low Cl- and H+, higher amounts of Na+ and K+, gastric pH 5-5.5.
• Eating: lots of HCL secretion, low amounts of Na+ and K+, more H+ and Cl-, gastric pH around 1.5.

Process of HCI Production

• HCI is made by parietal cells.
• CO2 in the blood diffuses into parietal cells and combines with H2O to form carbonic acid (H2CO3).
• Carbonic anhydrase cleaves carbonic acid into bicarbonate (HCO3-) and a proton (H+).
• Bicarbonate is secreted back into the blood in exchange for chloride (Cl-).
• A proton is secreted into the stomach lumen by the H+-K+-ATPase pump.
• In the stomach lumen, H+ and Cl- combine to form HCI.

Peptic Ulcers

• Peptic ulcers occur when there is an imbalance between damaging (acid) and protective (mucosal) forces.
• Duodenal ulcers are most commonly found in the first portion of the duodenum, often caused by hypersecretion of acid and sometimes by H. pylori.
• Patients with duodenal ulcers often feel better after eating because food neutralizes the acidity.
• Gastric ulcers are caused by a deficiency in mucin production to protect the stomach lining, sometimes due to NSAID use or other factors.
• Patients with gastric ulcers often feel worse with eating because food stimulates acid secretion.

Digestion and Absorption of Carbs

• Digestion of carbohydrates begins in the mouth with salivary amylase, breaking polysaccharides into smaller units.
• Pancreatic amylases further break down carbohydrates in the duodenum.
• Enzymes in the brush border of the small intestine (lactase, maltase, sucrase) complete the breakdown into monosaccharides.
• Absorbed monosaccharides (e.g., glucose, fructose, galactose) enter the bloodstream via a sodium-glucose cotransporter.

Digestion and Absorption of Proteins

• Pepsin and HCI in the stomach break down proteins into proteoses and peptones.
• Pancreatic enzymes further break down proteoses and peptones.
• Enzymes in the brush border of the small intestine digest these further into amino acids.
• Amino acids are absorbed via proton amino acid antiporter and sodium-amino acid symporter into the villi and transported to the liver.

Digestion and Absorption of Fats

• Fats are emulsified by bile salts, then broken down by pancreatic lipase into monoglycerides and glycerol.
• Monoglycerides are absorbed through lacteals and transported to the liver through lymphatic circulation.
• Glycerol and short-chain fatty acids are absorbed by capillaries in the villi and transported via the portal vein to the liver.

Absorption and Secretion

• Each section of the GI tract has specific nutrients it absorbs.
• Stomach: absorbs alcohol.
• Duodenum: absorbs most nutrients due to its tightly packed villi.
• Ileum: absorbs vitamin B12.
• Electrolyte transport occurs in the duodenum and jejunum through various transporters like sodium-proton exchanger, sodium-chloride transporter, and sodium-glucose cotransporter.
• Ileum and colon have specific electrolyte transporters (chloride bicarbonate exchanger, sodium-chloride cotransporter) to regulate electrolyte absorption / secretion.
• Diarrhea causes loss of bicarbonate in the feces.

Diarrhea

• Diarrhea is defined as an increase in stool mass, fluidity, or frequency, usually > 200 grams per day.
• Four types: secretory, osmotic, malabsorptive, exudative.

Bacterial Causes of Diarrhea

• Important factors of bacterial diarrhea include transmission modes, and symptoms.

Cholera

• Cholera toxin stimulates adenylate cyclase, which converts ATP to cAMP.
• This opens chloride channels in the intestinal lumen, leading to chloride secretion and water following.

Celiac Disease

• Celiac disease is an autoimmune disease triggered by ingested gluten.
• Gluten is metabolized into gliadin.
• Gliadin is deamidated by tTG and taken up by APCs presenting it to T cells.
• T cells stimulate B cells to produce anti-gliadin antibodies leading to villi thinning and loss of intestinal epithelium.

Inflammatory Bowel Disease

• Causes are not completely known but likely familial.
• Certain bacteria permeate through the epithelium more readily than others, taken up by dendritic cells, degraded and antigens presented to CD4 and CD8 cells.
• TH1 and TH17 lead to humoral B cells
• TH1 upregulates macrophages and cytotoxic T cells, causing damage to the epithelial cells.
• Immunosuppressants may reduce T cell response and reduce the inflammatory response.
• TNF alpha is the major component in this process

Crohn's Disease vs Ulcerative Colitis

• Crohn's disease: skip lesions, transmural inflammation, granulomas, fistulas, "cobblestone" appearance, affects any part of the GI tract from mouth-anus.
• Ulcerative colitis: continuous inflammation, affects distal colon and rectum, "lead pipe" appearance due to loss of haustra, high risk of colon cancer.

GI Motility

• Swallowing: involves the UES contracting, epiglottis tipping over the glottis, and peristalsis to move food down the pharynx.
• Gastric motility: accommodation (fundus of the stomach and proximal 1/3 of corpus allows food entry), emptying (remaining corpus, antrum, pylorus allow food digestion and passage into duodenum).
• Small intestine motility: duodenum serves 3 purposes (absorb enzymes from pancreas and gallbladder, form chyme, propagate remnant along tract), propagation, segmentation, pendular.
• Colonic motility: the colon contracts to make stool through mixing and propagating stool forward.

Motility Disorders

• Esophageal dysmotility (GERD, achalasia, dysphagia, strictures).
• Stomach dysmotility (gastroparesis).
• Colonic dysmotility (constipation, diarrhea).

Colon Cancer

• Colon cancer development involves a progressive series of mutations in key genes.
• Early stages are generally described as adenomas, and the later stage is the carcinoma.
• Multiple gene mutations lead to gross chromosomal alterations which lead to the disease.

Liver, Bile, and Bilirubin Metabolism

• Liver functions include bile production (albumin, cholesterol), storage (glycogen), detoxification, and regulating clotting. The liver converts unconjugated bilirubin to conjugated bilirubin for excretion.
• Bile consists of bile salts, bilirubin, water, electrolytes, and phospholipids.
• Bile salts emulsify fats, help with lipids absorption, and facilitate cholesterol excretion.
• Bilirubin metabolism involves the breakdown of heme from RBCs into bilirubin.

Splanchnic Circulation

• Splanchnic circulation is the blood supply to GI organs (celiac artery, SMA, IMA).
• Blood drains from the GI organs into the portal vein, which carries it to the liver for processing.
• The liver then drains processed blood into the inferior vena cava through hepatic veins.

Cirrhosis

• Liver disease where healthy liver tissue is replaced by scar tissue called fibrosis.
• Inflammation and cytokines (II-1, TNF, TGFB) stimulate stellate cells to differentiate into myofibroblasts.
• Myofibroblasts produce collagen causing progressive fibrosis.
• Kupffer cells also release cytokines to promote hepatocyte death.

Gallstones and Cholecystitis

• Gallstones (cholelithiasis): cholesterol stones, pigment stones (black=alcohol excess, brown=parasite infections), form when there is too much fat in bile or bile stasis.
• Acute cholecystitis: inflammation of gallbladder—often caused by gallstones blocking the cystic duct.
• Chronic cholecystitis: chronic inflammation of gallbladder; often caused by gallstones, clinical presentation is usually minimally symptomatic, however porcelain gallbladder is of concern.

Pancreas

• The pancreas has endocrine and exocrine functions.
• Islet cells produce insulin(lowers blood sugar) and glucagon(raises blood sugar).
• Acinar cells produce enzymes for protein and fat digestion.

Leptin and Ghrelin

• Leptin, ghrelin, and adiponectin help the body balance caloric intake and expenditure.
• Leptin increases energy expenditure.
• Ghrelin increases energy expenditure and stimulates fat buildup (anabolism).
• Adiponectin inhibits aging and increases energy expenditure.

Endocrinology

• Hormones act on distant cells through delivery in the bloodstream.
• Two types of feedback loops exist: positive and negative.
• The Hypothalamic/Pituitary Axis coordinates endocrine and nervous system messages.

Pituitary Mass Effect

• Bitemporal hemianopia, headaches, and increased ICP are associated with pituitary mass effect.

Prolactinoma

• Clinical features include galactorrhea, amenorrhea, and infertility in females and testicular atrophy and sexual dysfunction in males.
• Diagnosis involves measurement of prolactin levels and imaging (MRI).
• Treatment involves use of dopaminergic agents or surgery.

Growth Hormone Abnormalities

• Clinical features include gigantism or acromegaly in overproduction and energy loss, malaise, and depression with underproduction.
• Diagnosis involves measuring GH levels and imaging techniques.
• Treatment includes surgery, radiation, and/or octreotide in overproduction cases while underproduction cases require GH supplementation.

Adrenal Pathophysiology

• Adrenal cortex has 3 layers: zona glomerulosa (aldosterone), zona fasciculata (cortisol), and zona reticularis (estrogens and androgens).
• ACTH stimulates the adrenal gland, which mainly regulates glucocorticoid production.
• ACTH does not affect mineralocorticoids or other sex steroid hormone production in the adrenal gland.

Cushing's Disease

• Excess cortisol production usually caused by ACTH tumor or other diseases, leading to increase of glucocorticoid hormone production, which have systemic effects.
• Symptoms include central obesity, proximal muscle weakness, and skin striae.
• Diagnosis involves measuring AM and PM cortisol levels after a dexamethasone suppression test.
• Treatment includes surgery, radiation therapy, or medications.

Cushing's Syndrome

• Excess cortisol production caused by other sources than ACTH tumor.
• Clinical features can be similar to Cushing's disease.
• Diagnosis is similar to Cushing's disease.
• Treatment is similar to Cushing's disease.

Addison's Disease

• Causes include autoimmune destruction of the adrenal cortex resulting in deficiencies in mineralocorticoids and glucocorticoid hormones.
• Symptoms include weight loss, hypotension, and potentially Addisonian crisis.
• Diagnosis often involves measuring low cortisol and high ACTH levels along with a cortrosyn test.
• Treatment involves replacement of glucocorticoids and mineralocorticoids.

ACTH Abnormalities

• Clinical features include Cushing's Syndrome (central obesity, proximal muscle weakness, etc) or Addison's Disease (weight loss, malaise, etc).
• Diagnosis involves measuring AM and PM cortisol and performing a cortrosyn test, metyrapone stimulation test, etc.
• Treatment includes surgery, radiation, cortisol and mineralocorticoid replacement.

Thyroid Pathophysiology

• The thyroid produces thyroid hormones T3 and T4.
• Iodine is required for thyroid hormone synthesis.
• TSH regulates the production of T3 and T4.

TSH Abnormalities

• TSH abnormalities can lead to either hyperthyroidism or hypothyroidism.
• Hyperthyroidism is characterized by increased thyroid hormone production and increased metabolic rate.
• Symptoms include intolerance to heat, bulging eyes, tachycardia, and weight loss.
• Hypothyroidism results from decreased thyroid hormone production and decreased metabolic rate.
• Symptoms include intolerance to cold, weight gain, decreased mental attentiveness/memory, and lethargy.

Hyperthyroidism - Grave's Disease

• Grave's Disease is a type of hyperthyroidism—characterized by autoimmune antibodies that bind to TSH receptors.
• Elevated levels of circulating thyroid hormone T3 and T4. Thyroid stimulating hormone (TSH) is low due to negative feedback.
• Symptoms and signs of hyperthyroidism (intolerance to heat, nervousness, bulging eyes, etc).
• Diagnosis confirmed by imaging techniques (thyroid uptake with iodine scans) and blood tests (anti-TSH receptor antibodies).
• Treatment may involve medication or surgery.

Hypothyroidism

• Hypothyroidism is a condition with lowered levels of thyroid hormone T3 and T4, often resulting in slowed metabolic rate/function.
• Symptoms include loss of energy, weight gain, cold intolerance, and constipation.
• Signs include delayed return phase of DTRs, non-pitting edema, coarse skin, bradycardia, and hypothermia.
• Diagnosis involves measuring high TSH and low level of T3 and T4.
• Treatment generally includes thyroid hormone replacement (levothyroxine).

Pancreatic Endocrine Function

• Pancreas has both endocrine (e.g., producing insulin and glucagon) and exocrine (e.g., producing digestive enzymes) functions.
• The main endocrine function of the pancreas is to regulate blood glucose levels through the production and release of insulin and glucagon.

Glucose Uptake in the Cells

• Different types of glucose transporters (GLUTs) exist in various cells (e.g., GLUT-1 in RBCs, GLUT-3 in the brain).
• GLUTs are involved in facilitating glucose uptake.
• Glucose sensitivity to insulin varies throughout the body. Different cells have different energy needs and different capabilities to provide energy.

A Closer Look at Insulin Secretion

• Glucose entering beta cells increases ATP levels.
• High ATP inhibits K+ channels, depolarizes the cell, and triggers Ca2+ channels to open.
• Ca2+ influx stimulates insulin release into the bloodstream.

A Closer Look at How Insulin Works

• Insulin binding to its receptor activates a cascade of downstream signaling pathways, particularly involving tyrosine kinase activation.
• These pathways regulate numerous cellular processes such as transcription, translation initiation, translation elongation, and lipid synthesis.
• Important enzymes in these pathways regulate glucose metabolism.

Pathways of Carbohydrate Metabolism

• Gluconeogenesis: creates glucose from non-carbohydrate sources (liver, kidneys).
• Glycolysis: breaks down glucose for energy (cytoplasm).
• Glycogenesis: stores glucose as glycogen (liver, muscle).
• Glycogenolysis: breaks down glycogen to release glucose (liver, muscle).

Diagnostic Criteria for Diabetes

• Prediabetes (fasting blood glucose 100-125 mg/dL, postprandial 140-199 mg/dL, and/or HbA1c 5.7-6.4%).
• Diabetes (fasting blood glucose > 125 mg/dL, postprandial > 200 mg/dL, and/or HbA1c > 6.4%).

Type I Diabetes Mellitus

• Insulin deficiency due to autoimmune destruction of islet cells.
• Due to insufficient insulin, glucose cannot get into cells efficiently, resulting in elevated blood glucose and ketoacidosis.

Type II Diabetes Mellitus

• Insulin resistance—the body produces insulin, but the cells do not respond to it properly.
• Genetic mutations, obesity (decreased adiponectin, leptin), and other factors can contribute to insulin resistance.

Diabetic Complications

• Macrovascular diseases (e.g., atherosclerosis).
• Microvascular diseases (e.g., retinopathy, neuropathy, nephropathy). Infections and skin changes are also associated with diabetes.
• Age-related glucose end products (AGEs) can damage proteins in blood vessels, causing complications like atherosclerosis.

Infectious Disease Overview

• Encounter: Adherence to host cells, evasion of innate and adaptive immune system.
• Spread/Multiplication: production of toxins and enzymes.
• Evasion: inhibiting chemotaxis, killing phagocytes, or preventing host immune response.
• Survival within host phagocytes (evasion of killing mechanisms)

Infection Sources

• Endogenous: infections from inside the body (skin, colon, nose/oropharynx).
• Exogenous: infections from outside the body (fomites, vectors, humans, airborne).

This quiz covers essential aspects of the digestive system, including distinguishing features of Crohn's Disease versus Ulcerative Colitis, functions of the duodenum, swallowing mechanics, stool formation in the colon, and esophageal dysmotility. Test your knowledge on these critical processes and conditions of the human digestive system.