PASS GI.pdf

Chapter Eighteen: Gastrointestinal Physiology Embryology • • Develops in the 1st trimester Foregut • • • • Rotate 90° Blood supply: Celiac Trunk Controlled by: o Sympathetic – T 5-9 o Parasympathetic – Vagus nerve Gives rise to the GI, from mouth to second part of duodenum, including the respira...

Chapter Eighteen: Gastrointestinal Physiology Embryology • • Develops in the 1st trimester Foregut • • • • Rotate 90° Blood supply: Celiac Trunk Controlled by: o Sympathetic – T 5-9 o Parasympathetic – Vagus nerve Gives rise to the GI, from mouth to second part of duodenum, including the respiratory tract; Lungs Clinical Correlation Clinical Correlation Duodenal Atresia: Bilious vomiting after first feeding Double Bubble sign on x-ray Associated with Downs Syndrome Organ Development: Brain (1st) Heart (2nd) Kidney (3rd) Midgut • • • • • • Rotate 270° Blood supply: Superior Mesenteric Artery Controlled by: o Sympathetic – T 9-12 o Parasympathetic – Vagus nerve Extends from the second part of duodenum to the splenic flexure Develops in the YOLK SAC Must go through a 270-degree counterclockwise rotation as it migrates from yolk sac into abdominal cavity, via ciliary motion (dynein/kinesin) 515 Gastrointestinal Physiology Midgut Volvulus: Cause: Midgut wraps around the SMA cutting off its own blood supply. Si/Sx: Presents with severe abdominal pain, abdominal distension in the first week of life Dx: Abdominal CT with contrast (Birds beak sign) Rx: Surgery Kartagener’s Syndrome: (Midgut rotation requires Cilia) Cause: Dynein defect Si/Sx: Situs Inversus, Bronchiectasis Infertility Rx: Surgery Clinical Correlation Cystic Fibrosis: Cause: CFTR gene mutation at Chr.7 (Na / Cl channel) Fat malabsorption Infertility Obstructive Lung disease Clinical Correlation Clinical Correlation Cilia made of: Dynein– retrograde movement Membrane Movement: Microtubules Calcium ATP Kinesin– anterograde movement Hindgut • • • • • Septation Blood supply: Inferior Mesenteric Artery Controlled by: o Sympathetic – L 1-2 o Parasympathetic – Splanchnic nerve From splenic flexure to the anus WATERSHED AREA: The splenic flexure (has the least blood supply) 516 Gastrointestinal Physiology Ischemic infarct (Abdominal Angina): most common in elderly Cause: blood flow to a part of the bowel due to narrowing/blockage of the vessel Si/Sx: Pain that comes and goes (angina), usually after meal Dx: Angiogram Rx: Surgery Clinical Correlation Infarcted bowel: Pain is present all the time Labs: LDH Complication: Ileus 517 Gastrointestinal Physiology Figure 18.1 Abdominal Aorta Figure 18.2 Stomach Blood 518 Gastrointestinal Physiology Amniotic Fluid Production 80% is a filtrate of mom’s plasma 20% comes directly from the fetus To SUBTRACT: The baby must swallow (Neuromuscular reflex and a patent UGI) To ADD: The baby must then urinate into the fetal sac (Renal system) Role of Amniotic Fluid 1. Shock absorption 2. Decrease atmospheric pressure effect on fetus Polyhydramnios ( in amniotic fluid) 1. Fetus cannot swallow: • Autonomic dysfunction (Riley-Day syndrome) • Neuromuscular disease (Werdnig-Hoffman syndrome) 2. Fetus cannot digest: • UGI atresia (Esophageal atresia, Duodenal Atresia) Clinical Correlation Clinical Correlation Werdnig Hoffman Syndrome: Riley- Day Syndrome: • Familial Dysautonomia • Baby cries without tears Floppy Baby with fasciculations Oligohydramnios ( in amniotic fluid) Fetus cannot pee: o Renal agenesis/bladder obstruction o Metanephros did not develop o Ureteric bud fails to make contact with metanephros o Posterior urethral valves After 24 weeks of gestation, deliver the fetus immediately by C-section 519 Gastrointestinal Physiology Clinical Correlation Renal Agenesis associated with use of ACEI in mom Potter’s Syndrome Cause: Failure of fusion of Metanephros and ureteric bud to connect Si/Sx: Pulmonary aplasia or hypoplasia, and facial deformity and flattened facial features (due to atm. pressure) Prune Belly Syndrome Cause: Absence of abdominal wall musculature Si/Sx: Fetus is unable to bear down and raise abdominal pressure for urination no urination in utero Unable to urinate due to neuromuscular weakness Rx: Teach patient/parent to self-catheterize to prevent overflow incontinence Common complication - UTI Physiologic Organization 1. 2. 3. 4. 5. 6. Cephalic (thought of food) Oral Pharyngeal Esophagus UGI LGI Neurological SENSORY INFORMATION • • Found in the cortex #1 stimulation of salivation is visual (seeing food) THINKING about food HEARING about food SMELLING food • • CN 1 does not cross thalamus TOUCHING food Goes through sensory spinothalamic tract cortex CN10 GI 520 Gastrointestinal Physiology TASTING food 1. CEPHALIC PHASE • • • ALL sensory information must stop at the thalamus to reach the cortex Response is via the CORTICOBULBAR pathway (CN10 GIT) If the patient has had a total vagotomy, the signal does not reach GIT, can lead to anorexia because patient cannot enjoy food. So now, we do a highly selective partial vagotomy if needed in treatment of PUD. Clinical Correlation Peristalsis: Small IntestinePrimary peristalsis-> Segmentation Secondary peristalsis-> Migratory Myenteric Complex (MMC) Large Intestine Primary peristalsis-> Haustration Secondary peristalsis-> Mass movement LIMBIC SYSTEM • Responsible for basic urges but the Cortex can override it PINEAL GLAND • • • • • • • • Responsible for circadian rhythms Controlled by serotonin and melatonin (made from tryptophan) Light decreases melatonin and increases serotonin Darkness increases melatonin Catabolism is greatest in the morning: Example: Take vitamins, exercise in the AM to burn most fat Anabolism is greatest in the evening Example: Heavy meals in the evening will attribute to weight gain 521 Gastrointestinal Physiology Clinical Correlation Amphetamines: Cause the release of catecholamines (DA, NE, serotonin) at the presynaptic terminal Methylphenidate Pemoline Adderall Dexedrine LSD PCP Ecstasy HYPOTHALAMUS • • • • • • • Hunger center (Lateral nucleus) Stimulated by low glucose, neurotransmitters (NE, serotonin) • Anorexia Nervosa: Loss of firing at the hunger center Soft downy hair Low BMI (<18.5) Complications: Osteoporosis, Amenorrhea Rx: SSRI’s Satiety center (Ventromedial) Stimulus: glucose; gastric stretch; neurotransmitters (NE, serotonin) Prader-Willi: Lesion of the satiety center (Ventromedial) Uniparental disomy- one parent carrying both mutations Genomic Imprinting Paternal in origin Trinucleotide repeats Chromosome 15 Very aggressive appetite (Hyperphagia) Die due to overeating Rx: Supportive (Behavioral, diet, GH therapy, androgens) Controls MENSES Progesterone stimulates, hunger system Pregnancy- due to corpus luteum Controls TEMPERATURE: ANTERIOR Hypothalamus: cools (inhibits NE) Lesion anterior- die from hyperthermia POSTERIOR Hypothalamus: warms 522 Gastrointestinal Physiology Lesion posterior- die from hypothermia Neurotransmitters: NE and 5HT (more important) 80% of time stimulates satiety center 20% of time stimulates hunger center Amphetamines: (bases) MOA: They are taken up presynaptically, causing release of catecholamines Increases DA, NE, 5HT SE: DA causes Nausea / Vomiting; Tics (Neuromuscular – Basal Ganglia); Vertical nystagmus Methylphenidate- Ritalin USE: Narcolepsy, ADHD SE: Hypnogogic hallucinations as you fall asleep Pemoline SE: Hepatic necrosis (hepatitis)-off the market 2005 Dexedrine-Dexatrim USE: Weight loss + exercise and diet; OTC Adderall MOA: Dexedrine + racemic LSD SE: Colorful Hallucinations PCP SE: Hallucinations from Serotonin (violent, aggressive) Ecstasy SE: Hallucinations from Serotonin (stimulate thirst) 523 Gastrointestinal Physiology 2. ORAL PHASE When food is present in mouth salivary glands respond SALIVARY GLANDS • Parotid found in front of ear (serous) - water - CN 9 • Lingual found on the tongue (most serous) - CN 7 • Sublingual found under the tongue (most mucus) - CN 7 • Submandibular found under the lower jaw (mucus) - CN 7 Saliva: is basic (K and HCO ) Contains: • • • • • IgA: used to coat encapsulated organisms Lipase: fat digestion (negligible) Amylase: carbohydrate digestion Lysozyme: prevents adhesion so germs cannot stick to your teeth & gums HCO acts as a buffer against acidic environment Clinical Correlation IgA Protease bugs: Strep pneumonia H. Influenza Neisseria catarrhalis Salivary Production: • • Saliva in your mouth initially starts as isotonic (primary saliva) when entering the salivary ducts. More electrolytes are moved out of the salivary glands (via 3Na/2K ATPase, Cl /HCO antiport) hypotonic (secondary saliva) All salivary ducts are impermeable to water Clinical Correlation 3 Main sources of acid Food-fruits, soft drinks Bacteria- Strep mutant Reflux 524 Gastrointestinal Physiology Stress Response Parasympathetic first (2nd messenger: cGMP) • • • • • Acetylcholine - CNS: excitatory, PNS: activates muscles Methacholine - challenge for diagnosis of asthma Pilocarpine - sweat test (> 60) for diagnosis of CF, Treatment of open angle glaucoma (chronic) Carbachol - post op urinary retention (stimulate bladder emptying) Bethanechol - post op urinary retention The result of Parasympathetic response: saliva with an osmolarity ( blood flow isotonic plasma, no time to exchange at the ducts hypertonic salty solution) Sympathetic second (2nd messenger: cAMP) • • • • • Norepinephrine - 1, 2 and 1 receptors Epinephrine - has methyl group (hormone)- 2, 1, 2 and 1 receptors Ephedrine - OTC medication, decongestant Pseudoephedrine - stress incontinence, decongestant Phenylephrine - used to treat neurogenic shock via vasoconstriction The result of Sympathetic response: vasoconstriction blood supply to the GI saliva with an osmolarity (less saliva-more salt), hence less, cold hands, etc. Muscles of Mastication Embryology: 1st brachial arch Masseter: closes Temporalis: closes, moves jaw forward and back Medial Pterygoid: closes Lateral Pterygoid: Opens lower jaw, innervated by CN V3 mandibular branch Teeth: Incisors: CUT (10-12 months)-lower incisors come first Bicuspids: CHOP (15-18 MONTHS) Molars: GRIND (18-24 months) 525 Gastrointestinal Physiology Cystic Fibrosis • Etiology: MCC of malabsorption in children, post translational modification of Cl channel folding; gene present on chromosome 7 • Inheritance: Autosomal Recessive • Pathophysiology: Defective CHLORIDE transmembrane protein transport —> traps Cl in the cell —> negative charge on Cl attracts Na —> Na-K pump works harder and causes reabsorption of water out of the duct. Secretions thicken thickening of mucus secretions in the gland • Si/Sx: failure to thrive, multiple respiratory tract infections, greasy stools, salty sweat • Diagnosis: Pilocarpine sweat test • < 40 mmol/L - Normal • 40 – 60 mmol/L – Heterozygous Clinical Correlation • > 60 mmol/L - CF Bronchiectasis • Complications: CF • Meconium Ileus Kartagener Syndrome • Obstructive Lung disease CGD (Bronchiectasis) • Pancreatitis (mucus plugs) • Infertility (sperm cannot get out of epididymis) Clinical Correlation • Obliteration of vas deferens Pseudomonas and Staph. aureus affect: • Treatment: Antibiotics (cover Staph CF Aureus with 1 antibiotic and DM Pseudomonas with 2 antibiotics) Burn patients Neutropenic Staph Aureus Pseudomonas MSSA: Nafcillin (iv) Oxacillin (iv) Cloxacillin (po) Dicloxacillin (po) Flucloxacillin (po) Ciprofloxacin Special PCN: Carbenicillin Ticarcillin Mezlocillin Azlocillin Piperacillin Cefepime, ceftazidime, cefoperazone Gentamycin Aztreonam MRSA: Vancomycin (iv) Linezolid (iv/po) Daptomycin (iv) Tigecycline (iv) 526 Gastrointestinal Physiology 3. PHARYNGEAL PHASE Swallowing • Tip of tongue rises sides of tongue rise and fold medially tip of tongue rises to hard palate food rolls towards throat epiglottis closes off glottis (when food reaches trachea) bolus rolls over the epiglottis and touches the pharynx CN IX senses upper 1/3; CN X senses lower 2/3 UES opens, relaxes bolus drops into esophagus • Abnormalities of gag reflexes ( CN X) Aspiration pneumonia (anaerobic) REMEMBER As long as gag reflex is intact, patient should always be fed through upper GI If mouth is available feed them orally If mouth is wired, then use nasal, orogastric or nasogastric feeds If the face is burned and mouth/nose cannot be used and gag reflex is intact, use a percutaneous enterogastric tube If no gag reflex, use jejunostomy 4. ESOPHAGEAL PHASE Upper esophageal sphincter • • • • • • • • • Voluntary (skeletal muscle in upper 1/3 of esophagus) Squamous epithelium Constrictors of the pharynx Develops from the 4th pharyngeal arch Innervated by CN IX (stylopharyngeus) and CN X (all others) Nucleus Ambiguus Innervates the UES efferent: Vagus (motor CN 10) Dorsal motor nucleus Innervates the rest of GI: efferent Vagus (motor CN 10) Primary peristalsis (2nd messenger cGMP/ACH) Requires Vagus nerve and Auerbach’s plexus; begins just distal to the UES Secondary peristalsis (2nd messenger Ca2+ Calmodulin) Occurs due to distension Intrinsic to smooth muscle; can begin anywhere in GI 527 Gastrointestinal Physiology Lower Esophageal Sphincter • • • • • At the junction of esophagus and stomach Not under voluntary control Has to relax for passage of food/air Impaired relaxation Achalasia relaxation Reflux, GERD Clinical Correlation Muscles of upper 1/3 esophagus Superior pharyngeal constrictorinnervated by CN X Middle pharyngeal constrictorinnervated by CN X Inferior pharyngeal constrictorinnervated by CN X Stylopharyngeus–innervated by CN IX Clinical Evaluation 24hr pH Monitor Abnormal esophageal acid exposure 4-week trial of PPI’s if still having symptoms TPN (Total Parental Nutrition) Indications: Burn patients Crohn’s disease Preemie with Necrotizing enterocolitis GI surgery If GI is non-functional Contraindication to GI feeding Side effects: Gastrografin Esophagogram Best Initial test for dysphagia Achalasia: bird’s beak Diffuse esophageal spasm: corkscrew Upper Endoscopy Patients with h/o GERD > 5years to screen for Barrett’s esophagus Rx with PPI and follow with Upper endoscopy every 23years I.V. site infection Pancreatitis Hypertriglyceridemia Gallstones Fatty liver Esophageal Manometry Dysphagia to solids and liquids Diagnostic test for Achalasia and Diffuse esophageal spasm 528 Gastrointestinal Physiology Figure 18.3 Esophageal Disorders GERD When stomach content refluxes back into esophagus Etiology: Due to estrogen, abnormal relaxation of Lower Esophageal Sphincter (LES), alcohol, smoking, hiatal hernia, medication, collagen diseases Pathophysiology: Loss of LES tone, Obesity Diagnosis: Clinical, 24hr pH monitoring Complications: Stricture Barret’s esophagus Adenocarcinoma Treatment: Initial: Lifestyle modification - Weight loss, elevate head of bed, stop smoking/alcohol/ caffeine/spicy foods Mild disease: H blockers (ranitidine, cimetidine, famotidine) 529 Gastrointestinal Physiology Moderate disease: PPI (omeprazole, pantoprazole, lansoprazole, esomeprazole) Severe disease: Nissen fundoplication Esophagitis Tissue irritation or inflammation of the esophagus Virus: CMV, Herpes Fungi: Candida Drugs: Bisphosphonates, Iron Rx: Treat the cause Barrett’s Esophagus Columnar metaplasia (squamous epithelium replaced by columnar epithelium to handle acids better) Mallory Weiss Syndrome Linear tear in the mucus membrane of LES or upper stomach Due to retching, vomiting, binge drinking, eating disorders Rx: supportive (IVF), Cauterization or injection of epinephrine to the bleeding site if bleeding persists Boerhaave’s Transmural perforation of the lower esophagus due to retching and vomiting Choanal Atresia Lack of apoptosis: membrane that connects to pharynx did not dissolve Blue when feeding due to airway obstruction from the nipple/ pink when crying (baby breathes through the mouth) Esophageal atresia with distal TE fistula Blind pouch at proximal esophagus Most common congenital esophageal problem 530 Gastrointestinal Physiology Vomit on first feeding, drooling since birth X-Ray: big gastric bubble In uterus: polyhydramnios Rx: surgical removal of membrane H type TE fistula Coughing and choking with each feeding (milk comes through the nostril) Milk drips into trachea Esophageal Webs Strips of mucosa around the esophagus because apoptosis did not take place Associated with Plummer-Vinson syndrome (bleeding Iron def. anemia) risk of squamous cell carcinoma Plummer Vinson Syndrome UES Strips of mucosal tissue; lack apoptosis risk of esophageal cancer Young woman Microcytic anemia Schatzki Rings Intermittent dysphagia Strictures around the esophagus Associated with GERD, hiatal hernia, Lye ingestion Located above LES Dx: Barium swallow (will show distal narrowing) Achalasia • • • • Lack of Auerbach's plexus (ganglia) in distal esophagus Failure of neural crest migration GI tract will contract but won’t relax Progressive dysphagia to both solids and liquids 531 Gastrointestinal Physiology • • • • • Chagas disease (Trypanosoma Cruzi) risk of adenocarcinoma Si/Sx: Will start chocking and gagging when start on cereal (but ok with milk) Dx: • Bird’s beak sign on barium swallow • EGD with biopsy Manometry: LES pressure Rx: Pneumodilatation; Benznidazole; Nifurtimox Partial Vagotomy (the nerve causes the narrowing) Myotomy (to split tightened muscle fibers) Botulinum toxin (For patients with surgical contraindications) Clinical Correlation Chagas disease Trypanosoma Cruzi (Brazil and South America) Kissing bug Dilated esophagus Dilated cardiomyopathy Heart block Dilated colon Clinical Correlation Heart Block (LSD Loves Company) Legionella Salmonella Diphtheria Lyme's disease Chagas REMEMBER Neural Crest (MOTEL PPASS) Melanocytes Odontoblast Tracheal cartilage Enterochromaffin cells Laryngeal cartilage Pseudo unipolar cells Parafollicular All ganglia (Adrenal Medulla) Schwann cells Spiral membrane 532 Gastrointestinal Physiology Diverticula Zenker’s diverticulum Traction diverticulum Congenital Above the UES False diverticulum involving only two layers: mucosa and submucosa Halitosis and coughing up undigested food Most common in elderly because they lose muscle tone Occurs in the mid esophagus Dx: Barium Avoid NGT and upper endoscopy to prevent perforation Dx: Barium Avoid NGT and upper endoscopy to prevent perforation Rx: Surgery Rx: Surgery 5. UPPER GI STOMACH Figure 18.4 Gastric Physiology 533 Gastrointestinal Physiology Gastric Glands and Secretions • • Body • Epithelial cell • Mucus cells Mucus: protects the gastric mucosa from HCL • Parietal cells HCL: reduces pH of stomach, pepsinogen pepsin Intrinsic Factor (IF): absorption of Vitamin B 12 in the distal ileum • Chief cells: Pepsinogen, converted to pepsin for digestion of proteins Antrum • Mucus cells mucus and bicarbonate (HCO -) which are protective to GIT • G-cells gastrin into circulation Clinical Correlation Ach via CN X stimulate parietal cells (M3 receptor) Atropine (anticholinergic) blocks it Mast cells (H2 receptor): use Histamine to stimulate parietal cells Clinical Correlation Birds Beak Esophageal X-ray: Achalasia Abdominal X-ray: Volvulus On appearance: Myotonic Dystrophy Clinical Correlation 3 ways to protect the stomach • • • Mucus from goblet cells protect from acid erosion of GI Prostaglandin E pro- motes mucus production HCO3 - from alkaline tide 534 Gastrointestinal Physiology Stomach Phase Receptive Relaxation: Normal stomach pH is 1-2 LES relaxes; causes food to drop into stomach peristalsis begins in the middle 1/3 of the body of stomach. When the food drops into the stomach it will absorb some of the acid pH (alkalotic) signaling of G-Cells (antrum) to produce Gastrin release of IF and HCL from parietal cells Alkaline Tide Once gastrin touches the parietal cell, they will absorb water and CO2 from plasma Produces H2CO3 with carbonic anhydrase and break it down to H and HCO3HCO3 - will leave the cell and go into the plasma in exchange for Cl going into the cell (Alkaline tide). You will then have H and Cl inside the parietal cell. H within the parietal cell (High pH) is going into the lumen of the stomach (Low pH) to maintain the acidity of the stomach. Because the H is going from a lower gradient to a higher gradient it needs an ATPase (3H out and 2K in). This creates an electrical gradient, forcing Cl into the stomach to combine with H to make HCL. Increased levels of HCL will signal Chief cells to secrete pepsinogen and activate it to pepsin (to help with digestion of protein) GASTRIC PATHOLOGY Stress ulcers Stress parasympathetic discharge HCL sympathetic output vasoconstriction blood supply sloughing of the mucosa unprotected GI lumen ULCER Cushing’s ulcer: Patient with increased intracranial pressure Curling’s ulcer: Patients with burn injuries Gastritis MCC of upper GI bleeding in older children and adults Superficial erosion due to inflammation 535 Gastrointestinal Physiology Type A Gastritis Type B Gastritis Located in the body and fundus Frequency: 10% Due to antibodies to parietal cells gastric atrophy macrocytic anemia (B12 deficiency) Associated with adenocarcinoma Located in the antrum, near the pyloric area and duodenum Frequency: 90% Due to breakdown in barrier protection H. Pylori, hot/spicy foods, alcohol, meds (ASA) Associated with MALToma Peptic Ulcers Gastric ulcer Duodenal ulcer Located in the antrum of the stomach Frequency: 25% Etiology: 70% is associated with H. Pylori Si/Sx: pain gets worse with eating Dx: EGD Rx: underlying cause Associated with 20% risk of cancer, blood type A Located in the 2nd part of duodenum Frequency: 75% Etiology: 95% associated with H. Pylori, too much gastrin, hypercalcemia (ZE syndrome, MEN1) Si/Sx: pain is worse 30-40 min after eating and at night Dx: EGD Rx: Antibiotics Associated with 1% risk of cancer, blood type O Steroids and Aspirin block Prostaglandins, causing ulcers Steroids: MOA: (“IKISS”), Inhibits PLA2, Kills T cells and eosinophils, Inhibits macrophage migration Stabilizes endothelium, Stabilizes mast cells. USE: Allergy, chronic diseases, anti-inflammatory SE: CO2, ammonia GABA Aspirin MOA: irreversibly block Cox 1 and 2 USE: Anti-inflammatory, antipyretic, analgesic, antiplatelet SE: #1 cause of loss of Gastric lining Gastritis, cinchonism (vertigo, hearing loss, tinnitus) 536 Gastrointestinal Physiology Aspirin Toxicity Stages RR pCO2 pH Initial (Early) Moderate HCO3- Diagnosis N Respiratory alkalosis /N Combined Respiratory alkalosis with Metabolic acidosis Mixed Respiratory and Metabolic acidosis Severe (Late) Clinical Correlation Cinchonism Causes: • ASA • Quinidine • Quinine NSAIDs MOA: Reversibly inhibit COX USE: Anti-inflammatory, antipyretic, analgesic SE: Gastritis For ASA or NSAID induced gastric ulcers switch to Prostaglandin (PGE) Increase stomach lining, and work on parietal cells to inhibit acid production via HCO3Misoprostol (PGE1 analog) MOA: Replace PGE1, Gastric lining, absorption USE: induces mucus production SE: Dilation of cervix, Prevents implantation, rule out pregnancy before initiating 537 Gastrointestinal Physiology Alprostadil (PGE1 analog) USE: Vasodilation to keep PDA open Dinoprostone (PGE2 analog) USE: Softens cervix, increases uterine contractions COX 2 inhibitors Celecoxib MOA: block COX 2 USE: only one left, analgesic w/o gastric SE Rofecoxib, valdecoxib USE: off the market SE: Problem if on for more than 18 months and MI Regulation of H+ secretion block prostacyclin: clots Bezoar • • • A mass formed from the ingestion of indigestible/ inanimate materials Most common: hair due to trichotillomania obstruction at the pylorus Rx: Endoscopic removal Hiatal Hernia Type Sliding Frequency 90% Etiology #1 Obesity ( intraabdominal pressure) #2 Restrictive lung disease Pathology Fundus of stomach slides into esophageal hiatus Complications Treatment Rolling 10% Incidence of GERD Trauma in MVA Defect in the diaphragm Stomach strangulation, infarction, incarceration Weight loss Surgery H2 blockers Surgery: Nissen fundoplication 538 Gastrointestinal Physiology Menetrier's Disease • • • A rare disease characterized by thick rugal folds. There is goblet cell hyperplasia due to protein leaking out from GIT CLASSIC CLUE: Low Albumin EDEMA Looks like Nephrotic syndrome but kidneys and liver are intact Clinical Correlation 4 Causes of Edema Hydrostatic pressure Oncotic pressure Lymph obstruction Endothelial damage Pyloric Stenosis • • • • • Thickening of pyloric muscle, it takes 3-4wks for the muscle to hypertrophy Si/Sx: Projectile vomiting (3-4 wks. after birth) • Olive sign: an olive size mass on palpation (not always present) • String sign: passage of barium through the restricted pylorus Labs: hypokalemia, hyponatremic, hypocalcemia, hypochloremia, Metabolic alkalosis increased precipitation of Ca2+ stone formation Diagnosis: Ultrasound Rx: #1. Replace electrolytes #2. Pyloric Myotomy (split muscle fibers) Summary of digestion Protein: digestions starts in the stomach by pepsin and then finishes in the small bowel Sugar: digestion starts in the mouth, stalls in the stomach, and finishes in the small bowel Fat: digestion is negligible in the mouth, stalls in the stomach and finishes in the small bowel (takes the longest to digest) Chyme: is the digested food exiting the stomach 539 Gastrointestinal Physiology Dumping Syndrome Etiology: after resection of stomach (Billroth I, Roux-en-Y), the undigested food enters the small bowel too quickly bypassing the stomach release of large amounts of insulin. However, by the time insulin is released, the glucose in the small bowel has absorbed water osmotic diarrhea and hypoglycemic symptoms 30 to 40 minutes after a meal Rx: Eat small frequent meals that are low in sugars, then high in fat, then high in protein Pharmacology Antacids Calcium Carbonate (TUMS) MOA: The carbonate portion buffers the acid USE: Gastritis SE: Rebound acid increase: makes ulcers worse (Ca2+ is 2nd messenger for gastrin) Aluminum – OH (Rolaids) MOA: hydroxide buffer acids SE: Constipation from aluminum Mg – OH (Milk of Magnesium) MOA: hydroxide buffer acids SE: Diarrhea Gaviscon (base that absorbs acid) MOA: Buffer salt (Mg2+, Ca2+, Na+, Cu2+) USE: GERD Sucralfate (mixes with acid; therefore, needs acid in order to work) MOA: Sucrose + Sulfa necrotic tissue Lining coats ulcer (activated by acid), bind to 540 Gastrointestinal Physiology USE: Peptic Ulcer Disease SE: Cannot be absorbed Bismuth (Pepto-Bismol) MOA: Cofactor of GI lining, coats ulcers USE: Suffocates H. pylori, Traveler’s diarrhea SE: turns stool black H2 Blockers Cimetidine, Famotidine, Nizatidine, Ranitidine MOA: Block H2, HCl production USE: mild GERD, Gastritis SE: GI discomfort, bloating, gas, nausea, vomiting Cimetidine: Inhibits CYP 450 Proton pomp Inhibitors (PPI) Omeprazole, Lansoprazole, Esomeprazole, Pantoprazole, Rabeprazoles MOA: Block 90% production of acid in the Parietal cells USE: PUD, severe GERD, H. Pylori, Take one half hour before meal SE: GI discomfort, bleeding, bloating, gas, osteoporosis Clinical Correlation Drugs that motilin activity: Erythromycin Metoclopramide DUODENUM Duodenal Hormones • Secretin: releases from S cells HCO3– in pancreas via cAMP inhibits gastrin and gastric emptying and 541 Gastrointestinal Physiology • • • • • • CCK: released from I cells increases gallbladder contraction and release of digestive enzymes in the pancreas via IP3/DAG Motilin: released from M cells stimulates peristalsis in small intestine via IP3/DAG GIP: released from K cells decrease secretion of stomach acid, enhances Insulin release VIP: released from Auerbach's plexus purely inhibitory Somatostatin: released from D cells purely inhibitory Enterokinase: activates trypsinogen to trypsin which activates all other pancreatic enzymes PANCREAS Pancreatic Enzymes • • Zymogens: are inactive enzymes Trypsin (1st) is activated by enterokinase which then activates all other enzymes • Trypsin cuts to the right of Lys, Arg (Trip to L.A) • Chymotrypsin cuts to the right of Phe, Tyr, Trp • Elastase cuts to the right of Gly, Ala, Ser (G.A.S) • Aminopeptidase cuts to the right of the amino terminal amino acid • Carboxypeptidase cuts to the left of the carboxy terminal • Lipase • Amylase breaks down alpha 1,4 bonds • Fructose is only sugar with its own transport system (fastest metabolism) Clinical Correlation All amino acids are transported via Na+ cotransport channels 542 Gastrointestinal Physiology Disaccharides Monosaccharides Enzymes Deficiency Si/Sx. Comments Lactose Glucose + Galactose Lactase Lactose Intolerance N/V/D Bloating, gas -Lactose is the 1st enzyme to disappear during gastroenteritis and last to return (48hrs) -2nd mc. disaccharide deficiency Sucrose Glucose + Fructose Sucrase Sucrase deficiency N/V/D Bloating, gas MC. Primary disaccharidase deficiency Maltose 2 Glucose Maltase Alpha Dextrins 2 Glucose Alpha dextrinase Trehalase 3 Glucose Trehalase Abdominal Pain Management: Severe Abdominal Pain: Pancreatitis: mid epigastric pain Dissecting Abd. Aortic Aneurism: ripping/ tearing pain that radiates to the lower back Ischemic Bowel: elderly patient with A.fib, throws a clot from the heart into the splenic flexure Kidney stones: flank pain radiating to the groin, hematuria 1. NPO 2. NGT: for decompression, preventing perforation from gases 3. Fluid s ( iv NS +/- antibiotics 4. Meperidine (pain control, only opioid that does not constrict Sphincter of Oddi) 5. Abdominal X-Ray, US, CT scan Acute Pancreatitis Si/Sx: severe mid-epigastric pain radiating to the back (retroperitoneal) Etiology: In children 1. 2. 3. 4. Abdominal trauma Infections (#1 Coxsackie B, #2 Mumps) Hypertriglyceridemia Hypercalcemia 543 Gastrointestinal Physiology In adults 1. 2. 3. 4. Gallstones Alcohol Hypertriglyceridemia Hypercalcemia (Multiple Myeloma) Diagnosis: Labs: Amylase (sensitive, not specific), Lipase (specific, not sensitive) Abdominal US: R/O gall stones Abdominal X-Ray, CT Treatment: 1. 2. 3. 4. NPO NGT Fluids +/- antibiotics Meperidine Complications: Hemorrhagic pancreatitis • • • • • Bleeding into the retroperitoneum - 40% mortality Grey Turner’s sign: flank bruising Cullen’s sign: periumbilical bruising Dx: CT Rx: subtotal pancreatectomy Clinical Correlation Phlegmon The inflamed pancreas will be wrapped around with intestines swelling of both pancreas and intestines severe ileus 3rd spacing. Therefore, assume severe dehydration. Rx: Keep patient well hydrated Clinical Correlation Death of fatty pancreatic cells Fat Necrosis Dying pancreatic cells calcify and deposit in fat 544 Saponification Ca2+ Gastrointestinal Physiology Malabsorption • • In diabetic patients, there is no insulin production due to damaged pancreas No pancreatic enzymes for digestion greasy stools, vitamin deficiencies Pseudocyst • • • • • Lack of epithelial lining Fluid filled bubble in abdomen High persistent amylase If infected abscess Rx: Cystenterostomy (cyst is connected to intestine and drained) Ranson’s Criteria At admission At 48 hours AGE > 55 Hematocrit fall > 10% BUN rise > 5 GLUCOSE > 200 Serum Ca2+ < 8 LDH > 350 Arterial pO2 AST > 250 Base excess > 4 Interpretation Score Mortality 0-2 2% 3-4 15% 5- 40% 7-8 100% Clinical Correlation Clinical Correlation Currently APACHE II scoring system is used Chronic Pancreatitis • Calcification and fibrosis • Can lead to splenic vein thrombosis number prognosis 545 Gastrointestinal Physiology HEPATO-BILIARY SYSTEM Figure 18.5 Hepato-Biliary Bilirubin Figure 18.6 Bilirubin Metabolism 546 Gastrointestinal Physiology • • • Total bilirubin < 1 Responsible for color of stool and urine Is a breakdown product of heme from RBC’s being broken down Unconjugated (Indirect) bilirubin • • • Fat soluble jaundice Increased in pre-hepatic dysfunction Leads to kernicterus (deposition in Basal ganglia) Conjugated (direct) bilirubin • • Water soluble, excretion into the GI or kidney Conjugated in the liver by UDP glucuronyl transferase Urobilinogen • • • • • Bilirubin that is excreted in urine Gives yellow color to urine Urobilin is an oxidized form of urobilinogen Deficiency: Tea colored urine Liver diseases (hepatitis, cirrhosis): Impaired biliary excretion bilirubin spills into urine dark urine conjugated Stercobilin • • • • • Bilirubin that is excreted in the feces Gives brown color to stool Deficiency: Clay colored stool Newborns do not have gut flora to oxidize bilirubin into stercobilin colored stool CBD stone: bilirubin cannot enter duodenum clay colored stool clay- Albumin • • • Is required for transport of unconjugated bilirubin to the liver albumin unconjugated bilirubin Diseases: Nephrotic syndrome, Menetrier’s disease, Kwashiorkor, Cirrhosis 547 Gastrointestinal Physiology UDP-Glucuronyl transferase • • Made in the liver, made from glucose (all glycogen storage diseases jaundice) Deficiency: unconjugated bilirubin jaundice Unconjugated Hyperbilirubinemia Hemolysis Intravascular Etiology: vasculitis fibrinoid necrosis, where fibrin deposition in blood vessel shears the RBC Schistocytes (helmet/burr cells) Diseases: MAHA (Micro Angiopathic Hemolytic Anemia): DIC, TTP, HUS HELLP, Prosthetic valves Labs: • • • LDH Reticulocytes (> 35%) Schistocytes Haptoglobin Extravascular Etiology: RBC membrane defects Diseases: Autoimmune hemolytic anemia, HbSS, Hereditary Spherocytosis Si/Sx: Splenomegaly Crigler Najjar Syndrome Type I • • • Autosomal recessive Complete deficiency of UDP-glucuronyl transferase Incompatible with life Crigler Najjar Type II • • Partial deficiency of UDP-glucuronyl transferase (1/2 conj. + 1/2 unconj.) Si/Sx: hypoglycemia and jaundice 548 Gastrointestinal Physiology Gilbert’s Syndrome • • • • • Mild elevation of indirect bilirubin without hemolysis Normal liver enzymes (Glucuronyl transferase/Bilirubin diglucuronide) In Stress: Glucuronyl transferase is saturated creating a slight backup of bilirubin Normal PE Rx: Fluids Budd-Chiari Syndrome • Hepatic vein thrombosis Pain, ascites, hepatomegaly Conjugated Hyperbilirubinemia Rotors Syndrome • • • Defective bilirubin transport Less severe than Dubin-Johnson Increased Purine Coproporphyrin in urine Dubin-Johnson Syndrome • • • • Autosomal Recessive Defective bilirubin transport from liver to gall bladder Black pigment in hepatocytes and gallstones MCC of Cholecystectomy in children Cholestatic Jaundice • • • • • Post hepatic obstruction leading to conjugated bilirubin Charcot’s triad: Jaundice + fever + RUQ pain Reynold’s pentad: Jaundice + fever + RUQ pain + shock + altered mental status Gallstone Ileus: The gallstone gets stuck at the ileocecal valve obstruction Pneumobilia: air in the biliary tract 549 Gastrointestinal Physiology Newborn Choledochal cyst • • • • • • • Biliary tract cyst, a bubble in the way so bilirubin cannot drain Dx: US Rx: Surgical removal Biliary atresia Absent connection between gall bladder and duodenum Dx: US Rx: Surgical reconnection of GB with duodenum • • • Children and Adults Pancreatitis Gall Stones Lecithin Virchow’s Triad • • • cholesterol: fertile, fat, 40’s, female, obese, familial, DM, pregnancy bile salts: low fat diets, vegetarians lecithin: decreased veggies in diet Types of Gallstones Cholesterol Stones White/yellow Calcium Black/Green Bilirubinate Infectious stones Brown 80% 20% Salmonella 550 Radiolucent Radiopaque Hemolytic anemia E. Coli Gastrointestinal Physiology Figure 18.7 Gallstones Primary Sclerosing Cholangitis (PSC) • • • • • • Jaundice M>F Associated with Ulcerative colitis Increased risk for cholangiocarcinoma Dx: o P-ANCA o ERCP: beading and narrowing of the biliary system o Biopsy to differentiate it from PBC Rx: Ursodeoxycholic acid decreases frequency of gallstones Primary Biliary Cirrhosis • • • • • • Jaundice, fatigue, pruritus, Alkaline Phosphate Female in her 40’s or 50’s Xanthelasma: cholesterol plaques around the eyes Anti-mitochondrial antibodies Dx: Biopsy Rx: Ursodeoxycholic Acid decreases frequency of gallstones 551 Gastrointestinal Physiology After age of 40 years Cancer of the head of the Pancreas • • • • Painless jaundice Depression Trousseau syndrome: migratory thrombophlebitis Dx: conjugated bilirubin Abdominal CT Fat absorption Lecithin: • • • Helps EMULSIFY fats Comes from phosphatidylcholine Modified to make surfactant Bile acids: Cholesterol and Taurine duodenum Liver Cholic and Chenodeoxycholic acids Conjugated to Glycine Bile salt Stored in Gallbladder until contraction by CCK to enter the Emulsification of fats Entero-Hepatic Circulation • • • • 80% of bile salts used for emulsification in the duodenum are reabsorbed in the ileum and transported back to liver 20% excreted out of the body Recycling bile salts occurs during a meal De novo circulation • • • Liver makes bile salts from scratch Time consuming Occurs after Meal Cholesterol Synthesis Micelle: made from bile salts, fat, and lecithin acids 552 Lipase digests fats into fatty Gastrointestinal Physiology Fatty Acids have 3 forms: • • • • • Short chain fatty acids: absorbed through lacteals (lymphatics for fat only) and chylomicrons Medium chain fatty acids Do not require lacteals Cross intestinal wall by binding to albumin and get transported to the liver Long chain fatty acids: absorbed through lacteals with chylomicrons • Chylomicron: Chyme + Apo B48 + short, long-chain fatty acids VLDL: Very large density lipoprotein • • • • B-100 (from liver) 95% Triglyceride, 5% Cholesterol Requires C-II (from HDL) to enter adipose tissue Made directly in the liver IDL: Intermediate density lipoprotein • • • Requires ApoE 3 45% Triglyceride, 5% cholesterol Breakdown product of VLDL LDL: Low density lipoprotein • • Requires B100, LDL Receptor Breakdown product of IDL marked by Clathrin Pits HDL: High density lipoprotein • • • • Requires ApoA Activates LCAT Made in the liver Increased by moderate alcohol consumption, exercise, and niacin 553 Gastrointestinal Physiology Problem Consequences Type I LPL Deficiency (liver), Rx: diet alone Type IIa 90% LDL receptor down regulation Obesity LPL & CII Deficiency at Adipose Tissue Type IIb MC Type III Apo E problem (HDL) Type IV LPL (at adipose tissue) deficiency Type V CII Deficiency (HDL) MC in Diabetics Cholesterol Blood Levels Does not need fasting sample Normal Total Cholesterol 240, Optimal < 200 HDL 35-45 LDL < 100 (if diabetic < 70) Triglyceride < 150 Clinical Correlation Clinical Correlation Risk factors for CAD • DM • Obesity • Family history • cholesterol • fat • Male • HDL • HTN • Type A person • Sedentary life 4 ways to HDL • Exercise + diet • Weight loss • Moderate alcohol • Estrogen Hyperlipidemias • Signs: o Xanthoma: cholesterol patch on tendons (Achilles, elbow) o Xanthelasma: triglyceride patch around eyelids 554 Gastrointestinal Physiology Cholesterol Management Criteria • • • Normal < 200 200-240 Treat with Diet/Exercise > 240 Treat everybody LDL Management Criteria • • • Normal < 130 or if there is one risk factor < 100 100-130 Diet/Exercise > 130 Treat everyone PHARMACOLOGY • • Statins Lovastatin, Pravastatin, Simvastatin, Lovastatin, Atorvastatin, Cerivastatin, Rosuvastatin MOA: Blocks HMG-CoA reductase LDL, works best after 8PM USE: Hypercholesterolemia SE: Myositis, Hepatitis ASL & ALT • • • Bile acid resins • • • • • Cholestyramine, Colestipol MOA: Bind up bile salts and pulls out cholesterol for excretion With no cholesterol around the liver must pull more out from plasma USE: Hypercholesterolemia SE: Steatorrhea ( absorption of vitamins ADEK), gallstones Niacin • • MOA: HDL, TG, inhibit VLDL production SE: • Flushing ( Prostaglandins) prevented with aspirin • Histamine (prevented with antihistamines) • insulin resistance Exacerbates gout 555 Gastrointestinal Physiology Probucol • • • MOA: Inhibit cholesterol synthesis, absorption, USE: Add to other lipid lowering drugs SE: Dizziness, irregular heartbeat LDL breakdown Fibrates • • • • Gemfibrozil, Clofibrate MOA: Increases LPL activity USE: Hypertriglyceridemia SE: Myositis Triglyceride LOWER GI Stool spends the most time in: • • Children: ileum (to allow lymphoid cells to clean up harmful germs cecum colon) Adults: sigmoid (to allow the stool to go onto the rectum) If stasis diverticula will form SMALL INTESTINE Absorption in the Small Intestine Duodenum % Jejunum % Sugars 10 90 Amino Acids 10 90 Fats 10 80 A, D, E, K, B12 + IF 90 10 All else 10 90 PATHOLOGY Volvulus • • • 10 100 2+ Fe Ileum % Twisting of the bowel Colicky abdominal pain May lead to bowel necrosis 556 Gastrointestinal Physiology • • Enema: Birds beak appearance Rx: Surgery or endoscopic decompression Intussusception • • • • • • • • • One bowel segment telescopes into another Elderly, Children (episodic pain knees to chest) Currant Jelly stool Palpation: RUQ sausage shaped mass Associated with Henoch-Schoenlein Purpura Dx: Air contrast enema: Stacked coin appearance Both diagnostic and curative Children: Look for polyps as a cause Adults: Look for underlying cancer with endoscopy Appendicitis • • • • • • • • • • • • • • Appendix is the last part of the small bowel Reestablishes the gut flora MCC: Fecalith Number one cause of acute abdomen Fever, leukocytosis with left shift Early: Visceral pain (referred pain): Begins around umbilicus because appendix and umbilicus share the same dermatome (T10) Late: Somatic Pain (RLQ pain): Inflammation of appendix McBurney’s point: pain at 1/3 distance between umbilicus and anterior superior iliac spine Rovsing’s Sign: LLQ palpation causes RLQ pain Psoas Sign: RLQ pain with extension of hip Obturator Sign: RLQ pain with internal rotation of the right thigh Dx: CT Rx: Surgery, Incidental appendectomies can be done Complication: Perforation, Abscess Celiac Sprue • • • Anti-gluten; Anti-gliadin antibodies; anti endomysial antibodies Wheat allergy, diarrhea after eating bread Calcium-oxalate stones as a complication 557 Gastrointestinal Physiology • • • • Rash: Dermatitis Herpetiformis Fe absorption Dx: Biopsy shows blunting of villi in duodenum/jejunum Rx: Avoid Gluten in diet (wheat, oats, rye, barley) Tropical Sprue • • • • • • Infection in the Ileum Blunting of the mucosal surfaces in Ileum History of travel to Islands eosinophil count SE: Megaloblastic anemia Rx: TMP/SMX., Tetracycline for 3 to 6 months Whipple’s Disease • • • • Middle-aged male with arthritis Gram negative rods in the bowel wall, causing malabsorption Dx: Biopsy will show PAS+ foamy macrophages macrophages full of fat Rx: Erythromycin, Ceftriaxone or TMP/SMX for 1 year COLON Cecum • • • • • First and largest part of colon Cecal Cancer Uncommon/Poor prognosis Iron deficiency Anemia Melena Ascending colon • • • • Last chance to reabsorb fluids and electrolytes Many Na-K pumps controlled by aldosterone Retroperitoneal Low volume state is the most common cause of constipation patient 558 hydrate the Gastrointestinal Physiology Transverse colon • • • Primary peristalsis: Haustration Secondary peristalsis: Mass movement Watershed area: o Splenic flexure o blood supply: SMA ends before it and IMA begins just past it; mc site of infarcts Descending colon • • • Primary peristalsis: Haustration Secondary peristalsis: Mass movement Retroperitoneal Sigmoid colon • • • Sits at 90° angle with the descending colon and rectum Pubococcygeus muscle forms the sling that holds the rectum at 90° angle 90% CA presents with obstruction, bright red blood per rectum, Better prognosis PATHOLOGY Diverticulosis • • • • • Pocket in the bowel wall Painless bleeding Constipation Dx: Colonoscopy Rx: Increase Fiber in diet Diverticulitis • • • • • #1 cause of fistula formation in elderly Inflammation of the pocket Constipation, LLQ pain, fever, leukocytosis Dx: CT scan Rx: Antibiotics and surgery for recurrent episodes (r/o abscess) 559 Gastrointestinal Physiology Abetalipoproteinemia (Bassen Kornzweig Syndrome) • • • Apo B48 is missing low chylomicrons Fat Absorption Neuro, Adrenal, Adipose problems Ataxia Telangiectasia • • • • • DNA breakage repair problem IgA deficiency Cerebellar problem Spider veins all over body incidence of skin cancer Selective Ig-A Deficiency • • IgA deficiency sino-pulmonary infections Anaphylaxis with any transfusion (Rx: Washed RBC’s; use filter in IV line) Heavy Chain Disease • • • Autoimmune Lymphoma IgA producing plasma cells B cells in the Ileum lymph nodes Multiple Myeloma of the bowel wall Necrotizing Enterocolitis • • • • • Preterm infant Splenic flexure of colon Necrosis of the ileum Dx: X-ray will show Pneumatosis intestinalis (gas in bowel wall) Rx: Surgery Irritable Bowel Syndrome • • • Stress induced. Parasympathetic Sympathetic Parasympathetic Diarrhea Constipation Diarrhea Constipation Sympathetic Spastic colon • A diagnosis of exclusion; diagnosed by injecting glucagon and observing spasm Toxic Megacolon • • Severe distention of the colon that may result in perforation Hirschsprung’s disease 560 Gastrointestinal Physiology • • • Chagas Disease Ulcerative Colitis Rx: Triple Abx (Vancomycin, Aminoglycoside, Clindamycin) Surgery Ischemic Bowel • • • • • • MCC is Atherosclerosis al location: splenic flexure Pain that comes and goes, after food Bloody diarrhea Dx: Angiogram Rx: Surgery Eosinophilic enteritis • From feeding a child proteins (meat) too early Inflammatory Bowel Disease Crohn’s Disease (90%) Ulcerative Colitis (10%) Women Men From mouth to anus Starts in anus moves proximally to rectum HLA B-27 Non-granulomatous Granulomatous Type IV and Macrophages T cells Transmural Mucosal Creeping fat, cobblestone app. Sclerosing cholangitis (P-ANCA) Skip lesions Continuous; Lead pipe colon Melena Hematochezia Fistulas Pseudo polyps Skin infections Toxic megacolon Rx: Steroids, 5-ASA TNF-inhibitors (etanercept) Colon cancer risk: 10% at 10 years Annual colonoscopy at 7yrs post diagnosis 561 Gastrointestinal Physiology Hirschsprung’s disease • • • • • • Loss of both Auerbach’s and Meissner's plexus Rectum will not be able to relax Associated with Down syndrome Presentation: Failure to pass meconium, Constipation Dx: Barium Rx: remove part of the rectum that is affected Order of events to defecate 1. 2. 3. 4. 5. 6. 7. Relax pubococcygeus muscle Rectum falls in line with sigmoid colon Gravity and distention start moving stool down Once stool touches internal anal sphincter, 1st urge to defecate occurs Once stool touches external anal sphincter, last urge to defecate occurs Relaxation of pelvic floor muscles relaxes both sphincters No sympathetic input to defecation Encopresis When a child refuses to defecate due to pain PHARMACOLOGY • Anti-Gas o Simethicone (Gas X) o MOA: dissolves gas o USE: Gas excess o SE: CI in Nissen fundoplication • Anti-Diarrheal o Loperamide, Diphenoxylate o MOA: Bind gut wall opioid receptors inhibiting peristalsis, increases anal sphincter tone o USE: Diarrhea, Ulcerative Colitis and Cohn’s Dz ( Mortality) o SE: Constipation 562 Gastrointestinal Physiology • Stool Softeners 1. Psyllium (Metamucil) MOA: Cellulose USE: Constipation SE: Gas 2. Sorbitol MOA: Inhibits GI absorption, draws excess water into colon and promotes evacuation Can be found in green veggies/fruits 3. Phenolphthalein (Ex. Lax) MOA: gentle irritant of mucosa, stimulates peristalsis SE: Jet black colon (melanosis coli) 4. Docusate Sodium MOA: Pulls more water USE: Stool softener 5. Mineral Oil MOA: Lubricates the bowel, used in severe constipation (encopresis) • Cisapride MOA: Serotonin agonist USE: GERD SE: Cardiac Arrhythmia (torsade de pointe) increases motility (taken of the market) Metoclopramide • • • MOA: serotonin agonist, dopamine blocker USE: GERD, vertigo, dizziness, anti-emetic SE: Parkinsonian-like symptoms, extra pyramidal side effects Sulfasalazine / Sulfinpyrazone • • MOA: Anti-Inflammatory USE: IBD (Ulcerative Colitis, Cohn’s Disease) 563 Gastrointestinal Physiology UPPER GI BLEEDING • • • Newborns: swallowed maternal blood Children: epistaxis Adults: gastritis Massive UGI bleeding Children: Meckel’s Diverticulum • • • • • Remnant of vitelline duct (Omphalomesenteric duct) Rule of 2’s o Affects 2% of pediatric population o Located 2 feet from ileocecal valve o Peaks at 2 years of age o 2 cm in size o 2 types of ectopic mucosa: Gastric & Pancreatic o 2 times more common in males Presentation: Painless rectal bleed Dx: Technetium 99m Scan (Meckel’s Scan) Rx: Surgical Removal Adults: PUD 564 Gastrointestinal Physiology Lower GI Bleeding HEMATOCHEZIA Stable Unstable Colonoscopy Source identified? YES Resuscitate Interventional radiology Surgery NO EGD when stable -UGI bleed r/o Epinephrine Ligation Surgery Self-limiting No Iron def. anemia Continuous bleed or Iron def anemia bleed -UGI bleed r/o -No continuous bleed Supportive Colonoscopy Angiogram EGD Rx. UGI bleed +/- Small bowel bleed If recurrent or fail to identify site Colonoscopy Small bowel Enteroscopy Small bowel Enteroscopy Tc 99 scan Repeat EGD Tc 99 scan Surgery Repeat EGD Surgery 565 Chapter Nineteen: Renal Physiology and Pathology Normal Renal Physiology What organ develops first in the embryo? • 1St Brain • 2nd Heart • 3rd Kidney The kidney proper develops from the metanephros. The kidney proper will develop all the kidney structures up to and including the distal convoluted tubules. Ureteric Bud will form the rest of the kidney structures including: • Collecting duct • Major and minor calyces • Papilla • Hilum • Ureters The ureteric bud must contact the metanephros or the kidney will not develop If the kidney does not develop, the patient will suffer from oligohydramnios Mesonephros • The mesonephros (aka wolffian duct, in males only) gives rise to genitalia in males (i.e., testis, seminal vesicles, vas deferens, and epididymis) • All males have internal and external genitalia; and the internal genitalia is divided into two halves Internal Male genitalia (Two halves) • The Inner half of the internal male genitalia is when Mullerian inhibiting factor (MIF) suppresses the female internal (Mullerian) structures • To develop the internal male genitalia the embryo needs a Y chromosome • MIF prevents the Mullerian ducts and, therefore, the internal female genitalia from forming Clinical Correlation Clinical Correlation Mullerian Inhibiting Factor is secreted from the Sertoli cells of the testis 566 Males need testosterone to develop inner genitalia