Anatomy: Digestive & Endocrine

Mouth (oral cavity) → Pharynx → Esophagus → Stomach → Small intestine (duodenum → jejunum → ileum) → Large intestine (cecum → ascending colon → transverse colon → descending colon → sigmoid colon → rectum → anal canal). Total length ~9 meters (30 ft). Transit time: ~24-72 hours.

Teeth (mechanical digestion), Tongue (manipulation, taste), Salivary glands (parotid, submandibular, sublingual — secrete saliva with amylase), Liver (produces bile, detoxification, protein synthesis), Gallbladder (stores and concentrates bile), Pancreas (produces digestive enzymes and bicarbonate). Accessory organs are not part of the alimentary canal but aid digestion.

Mechanical digestion: physical breakdown of food into smaller pieces without changing chemical composition. Examples: mastication (chewing), churning in stomach, segmentation in small intestine. Increases surface area for enzymes. Chemical digestion: breakdown of food molecules by enzymes and acids into absorbable nutrients. Examples: amylase breaks starch → maltose, pepsin breaks proteins → peptides, lipase breaks fats → fatty acids + monoglycerides.

Mechanical: mastication (chewing) by teeth breaks food into smaller pieces; tongue manipulates food and forms bolus. Chemical: salivary amylase (ptyalin) begins starch digestion (starch → maltose). Salivary lipase begins minor fat digestion. Saliva also contains mucus (lubrication), lysozyme (antibacterial), IgA (immune defense), and bicarbonate (buffers pH ~6.8-7.0). Parotid gland = serous (amylase-rich); submandibular and sublingual = mixed.

Muscular tube (~25 cm) connecting pharynx to stomach. Passes through diaphragm at esophageal hiatus. Upper 1/3 = skeletal muscle, middle 1/3 = mixed, lower 1/3 = smooth muscle. Peristalsis propels bolus. Upper esophageal sphincter (UES) prevents air entry. Lower esophageal sphincter (LES/cardiac sphincter) prevents gastric reflux. No digestive enzymes produced here. GERD: LES dysfunction → acid reflux → heartburn.

1) Mucosa (innermost): epithelium (absorption/secretion), lamina propria (CT with blood/lymph, MALT), muscularis mucosae (local movement of mucosa). 2) Submucosa: dense CT with blood vessels, lymphatics, submucosal (Meissner's) plexus. 3) Muscularis externa: inner circular + outer longitudinal smooth muscle; myenteric (Auerbach's) plexus between layers; responsible for peristalsis. 4) Serosa/Adventitia (outermost): serosa (visceral peritoneum) in peritoneal organs; adventitia (CT) in retroperitoneal organs.

J-shaped organ. Regions: cardia (near LES), fundus (dome above cardia), body (largest portion), pylorus (antrum + canal + pyloric sphincter → duodenum). Lined with rugae (folds for expansion). Greater and lesser curvature. Gastric glands contain: parietal cells (HCl and intrinsic factor), chief cells (pepsinogen), G cells (gastrin), mucous neck cells (mucus), D cells (somatostatin). pH ~1.5-3.5. Capacity ~1-1.5 L.

Parietal cells: HCl (activates pepsinogen → pepsin, denatures proteins, kills microbes, creates acidic pH) and Intrinsic factor (essential for vitamin B12 absorption in the ileum; deficiency → pernicious anemia). Chief cells: Pepsinogen (inactive zymogen, activated to pepsin by HCl) — pepsin is a protease that digests proteins into polypeptides; also secrete gastric lipase.

Duodenum (~25 cm): receives chyme, bile, and pancreatic juice; most chemical digestion occurs here; Brunner's glands secrete alkaline mucus. Jejunum (~2.5 m): primary site of nutrient absorption; thick walls, many circular folds (plicae circulares) and long villi. Ileum (~3.5 m): absorbs bile salts and vitamin B12 (with intrinsic factor); Peyer's patches (lymphoid tissue); ileocecal valve controls entry into large intestine.

1) Plicae circulares (circular folds): permanent folds of mucosa and submucosa; slow chyme flow and increase surface area. 2) Villi: finger-like projections of mucosa; each contains a capillary network and a lacteal (lymphatic vessel for fat absorption). 3) Microvilli: tiny projections on apical surface of enterocytes forming the brush border; contain brush border enzymes (maltase, sucrase, lactase, peptidases). Together increase surface area greatly increased (historically cited as ~200 m², more recent estimates suggest ~32 m²).

Mouth: salivary amylase (starch → maltose). Stomach: pepsin (proteins → peptides), gastric lipase (minor fat digestion). Pancreas → duodenum: pancreatic amylase (starch), trypsin/chymotrypsin/carboxypeptidase (proteins), pancreatic lipase (fats → fatty acids + monoglycerides), nucleases (nucleic acids). Brush border: maltase, sucrase, lactase (disaccharides → monosaccharides), peptidases (dipeptides → amino acids).

Bile is produced by hepatocytes in the liver, stored and concentrated in the gallbladder, and released into the duodenum via the common bile duct. Bile salts (conjugated bile acids) EMULSIFY fats — breaking large fat globules into smaller droplets (increases surface area for pancreatic lipase). Bile is NOT an enzyme; it does not chemically digest fat. Bile also helps absorb fat-soluble vitamins (A, D, E, K) and eliminates bilirubin and cholesterol.

Cecum receives ileal contents at ileocecal valve; appendix (lymphoid tissue) attaches to cecum. Ascending → transverse → descending → sigmoid colon → rectum → anal canal. Functions: absorbs water and electrolytes (Na⁺, K⁺, Cl⁻), compacts feces, absorbs vitamins produced by bacteria (vitamin K, B vitamins), houses gut microbiota (fermentation of fiber → short-chain fatty acids). Haustral contractions and mass movements propel contents. Defecation reflex via rectum and internal/external anal sphincters.

1) Produces bile (500-1000 mL/day). 2) Detoxification of drugs, alcohol, and toxins (cytochrome P450 enzymes). 3) Protein synthesis: albumin, clotting factors (I, II, V, VII, IX, X), complement proteins. 4) Glycogen storage and gluconeogenesis (blood glucose regulation). 5) Lipid metabolism (cholesterol, lipoproteins). 6) Stores fat-soluble vitamins (A, D, E, K) and iron/copper. 7) Converts ammonia to urea (urea cycle). 8) Bilirubin metabolism (conjugation for excretion in bile). 9) Phagocytosis by Kupffer cells.

Exocrine (~99%): acinar cells secrete digestive enzymes (trypsinogen, chymotrypsinogen, procarboxypeptidase, pancreatic lipase, amylase, nucleases) and duct cells secrete bicarbonate (NaHCO₃) to neutralize acidic chyme. Secreted into duodenum via pancreatic duct. Endocrine (~1%): Islets of Langerhans — alpha cells (glucagon, raises blood glucose), beta cells (insulin, lowers blood glucose), delta cells (somatostatin, inhibits both), PP cells (pancreatic polypeptide).

Unique venous system that carries nutrient-rich, deoxygenated blood from the GI tract (stomach, intestines, spleen, pancreas) directly to the liver via the hepatic portal vein BEFORE it enters general circulation. This allows the liver to process absorbed nutrients, detoxify harmful substances, and regulate blood glucose levels. Blood then exits the liver via hepatic veins → IVC. A portal system connects two capillary beds in series.

Gastrin is produced by G cells in the pyloric antrum of the stomach. Released in response to: stomach distension, peptides in stomach, vagal stimulation (parasympathetic). Effects: stimulates parietal cells to secrete HCl, stimulates chief cells (pepsinogen), promotes gastric motility, stimulates growth of gastric mucosa. Inhibited by low pH (<2) via somatostatin release from D cells (negative feedback). Zollinger-Ellison syndrome: gastrin-secreting tumor → excess acid → ulcers.

Both produced by enteroendocrine cells in the duodenal mucosa. Secretin: released in response to acidic chyme entering duodenum. Stimulates pancreatic bicarbonate secretion (neutralizes acid), bile secretion by liver, inhibits gastric acid secretion and motility. CCK (cholecystokinin): released in response to fats and proteins in duodenum. Stimulates gallbladder contraction (bile release), pancreatic enzyme secretion, inhibits gastric emptying, promotes satiety. Both inhibit gastrin.

Produced by K cells in the duodenum and jejunum. Released in response to glucose and fats in the small intestine. Primary function: stimulates insulin release from pancreatic beta cells (incretin effect — oral glucose triggers more insulin than IV glucose). Also mildly inhibits gastric acid secretion and motility. GIP and GLP-1 are the two main incretins. Incretin effect is reduced in Type 2 diabetes. GLP-1 receptor agonists (e.g., semaglutide) are used for diabetes and weight loss.

Hypothalamus, Pituitary (anterior + posterior), Pineal, Thyroid, Parathyroid (4), Thymus, Adrenal (cortex + medulla) (2), Pancreatic islets, Ovaries (2)/Testes (2). Other tissues with endocrine function: heart (ANP/BNP), kidneys (EPO, renin, calcitriol), adipose tissue (leptin), GI tract (gastrin, secretin, CCK, GIP, GLP-1), placenta (hCG, progesterone, estrogen).

Releasing and inhibiting hormones that control the anterior pituitary: GnRH (gonadotropin-releasing), TRH (thyrotropin-releasing), CRH (corticotropin-releasing), GHRH (growth hormone-releasing), Somatostatin (GH-inhibiting), Dopamine/PIH (prolactin-inhibiting). Also synthesizes ADH (antidiuretic hormone/vasopressin) and Oxytocin — these are made in hypothalamic neurons but stored and released from the posterior pituitary.

GH (growth hormone): liver, bone, muscle (growth, metabolism). TSH (thyroid-stimulating): thyroid (T3/T4 release). ACTH (adrenocorticotropic): adrenal cortex (cortisol release). FSH (follicle-stimulating): ovaries (follicle development), testes (spermatogenesis). LH (luteinizing): ovaries (ovulation, corpus luteum), testes (testosterone from Leydig cells). Prolactin (PRL): mammary glands (milk production). Mnemonic: FLAT PiG (FSH, LH, ACTH, TSH, Prolactin, GH).

ADH (Antidiuretic Hormone/Vasopressin): produced by supraoptic nucleus of hypothalamus. Acts on collecting ducts of kidney (inserts aquaporin-2 channels → water reabsorption). Also causes vasoconstriction at high concentrations. Released in response to increased plasma osmolarity or decreased blood volume. Deficiency → diabetes insipidus (dilute urine, excessive thirst). Oxytocin: produced by paraventricular nucleus. Stimulates uterine contractions during labor and milk letdown during breastfeeding. Involved in bonding and trust. Both use positive feedback.

T4 (thyroxine, ~90%) and T3 (triiodothyronine, ~10% but more active): produced by follicular cells. Require iodine for synthesis. Functions: increase basal metabolic rate (BMR), increase O₂ consumption and heat production (calorigenic effect), essential for normal growth and development (especially CNS in infants). Calcitonin: produced by parafollicular (C) cells. Lowers blood calcium by inhibiting osteoclasts and promoting Ca²⁺ deposition in bone. Minor role in adults.

Hypothalamus releases TRH → Anterior pituitary releases TSH → Thyroid releases T3/T4. T3/T4 exert negative feedback on both hypothalamus (↓ TRH) and anterior pituitary (↓ TSH). Most T4 is converted to active T3 in peripheral tissues by deiodinases. Thyroid hormones are lipid-soluble (bound to thyroid-binding globulin in blood) and act on nuclear receptors to alter gene expression.

4 small glands on the posterior thyroid. Chief cells secrete PTH (parathyroid hormone) in response to LOW blood Ca²⁺. PTH actions (raises blood Ca²⁺): 1) Stimulates osteoclast activity → Ca²⁺ released from bone. 2) Increases Ca²⁺ reabsorption in kidneys. 3) Stimulates kidneys to activate vitamin D (calcitriol) → increases intestinal Ca²⁺ absorption. 4) Increases phosphate excretion by kidneys. PTH is the most important regulator of blood calcium.

Three zones, three hormone types (mnemonic: GFR — Salt, Sugar, Sex): Zona Glomerulosa → Mineralocorticoids (aldosterone): regulates Na⁺/K⁺ balance, blood pressure (Na⁺ reabsorption, K⁺ excretion in kidneys; part of RAAS). Zona Fasciculata → Glucocorticoids (cortisol): stress response, increases blood glucose (gluconeogenesis), anti-inflammatory, immunosuppressive. Zona Reticularis → Androgens (DHEA): weak androgens converted to testosterone/estrogen peripherally.

The adrenal medulla is modified sympathetic ganglion (neural crest origin). Chromaffin cells secrete catecholamines: Epinephrine (~80%) and Norepinephrine (~20%) into the blood. Functions ('fight or flight'): increase HR, BP, bronchodilation, glycogenolysis, lipolysis, pupil dilation, redirect blood to skeletal muscles. Released in response to sympathetic stimulation (preganglionic ACh). Pheochromocytoma: tumor of adrenal medulla → episodic hypertension, tachycardia, headache, sweating.

Primary glucocorticoid from zona fasciculata. HPA axis: Hypothalamus (CRH) → Anterior pituitary (ACTH) → Adrenal cortex (cortisol). Negative feedback on both hypothalamus and pituitary. Functions: raises blood glucose (gluconeogenesis, glycogenolysis), anti-inflammatory (inhibits prostaglandins, leukotrienes), immunosuppressive (decreases WBCs, cytokines), mobilizes fatty acids and amino acids, helps cope with stress. Diurnal rhythm: peaks in early morning. Chronic excess → Cushing's syndrome.

Produced by beta cells of pancreatic islets (Islets of Langerhans). Released when blood glucose rises (after a meal). Actions (anabolic — lowers blood glucose): 1) Increases glucose uptake by cells (inserts GLUT4 transporters in muscle and adipose). 2) Stimulates glycogenesis (glucose → glycogen in liver/muscle). 3) Promotes lipogenesis (fatty acid synthesis). 4) Stimulates protein synthesis. 5) Inhibits gluconeogenesis and glycogenolysis. Only hormone that lowers blood glucose.

Produced by alpha cells of pancreatic islets. Released when blood glucose drops (fasting, between meals, exercise). Actions (catabolic — raises blood glucose): 1) Stimulates glycogenolysis (glycogen → glucose in liver). 2) Stimulates gluconeogenesis (amino acids/glycerol → glucose in liver). 3) Stimulates lipolysis (fat → fatty acids + glycerol). Glucagon and insulin are antagonistic and work together to maintain blood glucose homeostasis (~70-100 mg/dL fasting).

Water-soluble (proteins, peptides, amines except thyroid): cannot cross plasma membrane. Bind to extracellular receptors → activate intracellular second messenger systems (e.g., cAMP, IP3/DAG). Fast onset, short duration. Examples: insulin, epinephrine, GH, ADH. Lipid-soluble (steroids, thyroid hormones): cross plasma membrane. Bind intracellular/nuclear receptors → act as transcription factors → alter gene expression → new protein synthesis. Slow onset, long duration. Examples: cortisol, estrogen, T3/T4, aldosterone.

Negative feedback: the product of a pathway inhibits earlier steps in the pathway, maintaining homeostasis. Example: Low T3/T4 → hypothalamus releases TRH → anterior pituitary releases TSH → thyroid produces T3/T4 → rising T3/T4 levels inhibit TRH and TSH release → thyroid hormone production decreases. If T3/T4 drops, inhibition is removed, and the cycle restarts. This maintains hormone levels within a narrow range.

Positive feedback: the product amplifies the stimulus, driving the process to completion. Examples: 1) Oxytocin during labor: uterine contractions stretch cervix → oxytocin release → stronger contractions → more oxytocin → continues until delivery. 2) LH surge: rising estrogen from maturing follicle eventually triggers massive LH release from anterior pituitary (instead of inhibiting it) → triggers ovulation. 3) Blood clotting cascade (platelet plug formation amplifies clotting factors). Positive feedback loops always have an endpoint.

Deficient thyroid hormone production. Causes: Hashimoto's thyroiditis (most common — autoimmune destruction), iodine deficiency (endemic goiter), thyroid surgery, radioiodine therapy, pituitary failure (secondary). Symptoms: fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, bradycardia, myxedema (facial puffiness), mental sluggishness, increased cholesterol. In infants: cretinism (intellectual disability, growth failure). Treated with levothyroxine (synthetic T4).

Excess thyroid hormone. Most common cause: Graves' disease (autoimmune — TSI antibodies stimulate TSH receptors → thyroid overactivity). Other causes: toxic multinodular goiter, toxic adenoma. Symptoms: weight loss despite increased appetite, heat intolerance, sweating, tachycardia, palpitations, tremor, anxiety, diarrhea, exophthalmos (bulging eyes, Graves' specific), goiter. Treatment: antithyroid drugs (methimazole, PTU), radioactive iodine ablation, surgery.

Chronic excess of cortisol (glucocorticoid). Most common cause: exogenous (iatrogenic — long-term corticosteroid medication). Endogenous: ACTH-secreting pituitary adenoma (Cushing's disease, ~70%), adrenal tumor, ectopic ACTH (e.g., small cell lung cancer). Signs: central obesity (trunk), moon face, buffalo hump (dorsocervical fat pad), thin skin with purple striae, easy bruising, hyperglycemia, hypertension, osteoporosis, immunosuppression, muscle weakness (proximal).

Primary adrenal insufficiency — destruction of adrenal cortex → deficiency of cortisol AND aldosterone (and adrenal androgens). Most common cause: autoimmune adrenalitis. Also: TB, adrenal hemorrhage, metastatic cancer. Symptoms: fatigue, weight loss, hypotension (orthostatic), hyperpigmentation (elevated ACTH stimulates melanocytes), salt craving (hyponatremia from low aldosterone), hyperkalemia, hypoglycemia. Adrenal crisis: life-threatening hypotension and shock. Treatment: lifelong glucocorticoid + mineralocorticoid replacement.

Type 1 (~5-10%): autoimmune destruction of beta cells → absolute insulin deficiency. Usually childhood/adolescent onset. Requires insulin therapy. Risk of DKA (diabetic ketoacidosis — lipolysis → ketones → metabolic acidosis). Type 2 (~90-95%): insulin resistance ± relative insulin deficiency. Usually adult onset (increasingly in youth). Associated with obesity, sedentary lifestyle, genetics. Treated with lifestyle changes, oral hypoglycemics (metformin first-line), GLP-1 agonists, and eventually insulin if needed. Risk of hyperosmolar hyperglycemic state (HHS). Both → chronic complications: retinopathy, nephropathy, neuropathy, cardiovascular disease.

Both caused by excess growth hormone (GH). Gigantism: GH excess BEFORE epiphyseal plate closure (childhood) → proportional excessive height. Acromegaly: GH excess AFTER epiphyseal plate closure (adulthood) → enlargement of hands, feet, jaw (mandible), brow ridge, soft tissue thickening, organ enlargement (cardiomegaly), coarsened facial features. Usually caused by GH-secreting pituitary adenoma. Diagnosed by elevated IGF-1 and failure to suppress GH with oral glucose. Treatment: surgery (transsphenoidal), somatostatin analogs (octreotide), GH receptor antagonist (pegvisomant).

Ovaries: Estrogen (estradiol — primary): develops/maintains female secondary sex characteristics, endometrial growth, bone density, lipid profile. Progesterone: maintains endometrium for pregnancy, inhibits uterine contractions, raises body temperature. Inhibin: negative feedback on FSH. Testes: Testosterone (from Leydig cells): develops/maintains male secondary sex characteristics, spermatogenesis (with FSH), muscle/bone mass, libido. Inhibin (from Sertoli cells): negative feedback on FSH.

Pineal gland: melatonin (derived from serotonin/tryptophan). Regulates circadian rhythms (sleep-wake cycle). Secretion increases in darkness, decreases in light. Involved in seasonal rhythms. May play role in puberty timing. Thymus: thymosin and thymopoietin. Essential for T lymphocyte maturation (T-cell education — positive and negative selection). Most active in childhood; involutes (shrinks and replaced by adipose) after puberty. Removal in adults has minimal immune effect.

Leptin: produced by adipose tissue (fat cells). Signals satiety — higher body fat → more leptin → decreases appetite and increases energy expenditure (acts on hypothalamus). Obesity often involves leptin resistance (high leptin but reduced response). Ghrelin: produced by stomach (fundus). 'Hunger hormone' — levels rise before meals, stimulates appetite and GH release. Levels decrease after eating. Gastric bypass surgery reduces ghrelin-producing tissue → reduced appetite.

Peristalsis: coordinated waves of smooth muscle contraction and relaxation that propel contents in one direction (orad to caudal). Occurs throughout GI tract. Circular muscle contracts behind bolus, longitudinal muscle contracts ahead, pushing contents forward. Segmentation: localized contractions of circular muscle that mix and churn chyme WITHOUT significant forward movement. Primary motility pattern in the small intestine. Increases contact with absorptive surfaces and digestive enzymes.

Stores and concentrates bile (5-10x) produced by the liver. Located on the inferior surface of the liver. When fats enter the duodenum → CCK released → gallbladder contracts and sphincter of Oddi relaxes → bile flows through cystic duct → common bile duct → into duodenum at the hepatopancreatic ampulla (ampulla of Vater). Gallstones (cholelithiasis): precipitated cholesterol or bilirubin; can block cystic/common bile duct → biliary colic, cholecystitis, obstructive jaundice, pancreatitis.

Bile salts secreted into duodenum emulsify fats → absorbed in the ileum (95% recycled) → return to liver via hepatic portal vein → re-secreted into bile. This cycle occurs 6-8 times per day. Loss of ileum (Crohn's disease, surgical resection) disrupts bile salt reabsorption → fat malabsorption (steatorrhea) and fat-soluble vitamin deficiency. Bile acid sequestrants (cholestyramine) interrupt this cycle to lower cholesterol.

The vagus nerve (CN X) is the main parasympathetic nerve to the GI tract (from esophagus to splenic flexure of colon). Stimulates: gastric acid secretion (via ACh on parietal cells and gastrin release from G cells), pancreatic enzyme and bicarbonate secretion, gallbladder contraction, increased GI motility and peristalsis, relaxation of sphincters. The cephalic phase of digestion (sight, smell, thought of food) is mediated by vagal stimulation. Vagotomy was historically used to treat peptic ulcers.