Unit I, week 1 Flashcards
Smooth muscle contraction review
Actin = thin filament, myosin = thick filaments with cross bridges extending to contact thin filaments
Thin:thick filaments = 10:1 (skeletal muscle is 2:1)
Ca2+ entry into cell → Ca2+ + calmodulin → activate myosin light chain kinase → phosphorylates myosin → allows cross-bridge formation (cycling) to occur → smooth muscle contraction
Myosin light chain phosphatase breaks down this process and stops contraction
Types of motility in GI tract
Segmentation
Peristalsis
Segmentation
MIXING
Contraction is isolated, not coordinated with movement above and below, propel contents in both directions
When contracting area relaxes, contents flow back into original segment → mixing without net propulsion
Peristalsis
propulsive movement
Contractions of adjacent segments coordinated in proximal and distal manner → net propulsion of contents
Describe the general mechanism of peristalsis
Bolus of food distends intestinal wall → formation of contractile ring just proximal to bolus that pushes bolus distally
Longitudinal muscle contracts compacting bolus
At same time, intestine distal to bolus relaxes = Receptive Relaxation
Coordination requires nerves of myenteric plexus
In the stomach, peristalsis requires _______ coordinated by ________
BERs
vagal input
Smooth muscle in GI tract
Unitary (single unit) cell type:
- Held together by adherens junctions
- Communicate electrically via gap junctions
- Pacemaker cells with spontaneous activity
- Intrinsically produces BER and muscle tone without tension (myogenic properties)
- Tension comes from NTs acting on muscle → role of ANS
Innervation of intestinal smooth muscle (3)
Sympathetic: epinephrine inhibits digestive function
Parasympathetic: rest-digest, sit-shit
ENS: bidirectional signalling between gut wall and ANS innervation
Basic electrical rhythm (BER)
cyclical changes in membrane polarization
Intrinsic property of smooth muscle cells in a given location (no external stimulus required) = MYOGENIC
Each depolarization does NOT cause contraction - contraction only occurs when depolarization exceeds specific membrane potential
–> Require NT input (ACh)
When membrane potential reached, muscle contracts at BER frequency
Force of contraction proportional to number of APs
BERs as you move along the GI tract
Different as you move along GI tract:
Stomach BER = 3 cycles per minute
Duodenum BER = 12 cycles per minute
Want things moving faster in the front so there isn’t backing up
Swallowing (deglutition)
swallowing initiated voluntarily but then sensory receptors in pharynx send impulses to swallowing center in brainstem → coordinate subsequent involuntary events
Phases of swallowing (3)
1) Voluntary
2) Pharyngeal
3) Esophageal
Voluntary swallowing phase
-what two steps of swallowing happen in this phase?
oral cavity bolus pushed by tongue to oropharynx
1) Tongue separates portion of food, moves it back into pharynx
2) Food pushes soft palate upward → constrictor muscle contracts, closing off nasopharynx → SWALLOWING NOW A REFLEX FROM HERE (involuntary)
Pharyngeal swallowing phase
-what two steps of swallowing happen in this phase?
directs food into esophagus, keeps it out of trachea
3) Respiration inhibited for 1-2 seconds centrally → larynx rises and glottis closes to prevent bolus from entering trachea
4) Upper esophageal sphincter (UES) relaxes
Esophageal swallowing phase
What step happens in this phase
5) Coordinated contraction (peristaltic wave) of middle and lower constrictor muscles propel bolus down esophagus
Esophageal peristalsis
Peristalsis propels bolus down esophagus in 5 seconds, and LES relaxes to allow bolus into stomach
LES prevents reflux of acid gastric contents into esophagus, but NOT a valve - just a thickening of muscle wall
What nerve controls esophageal peristalsis, what happens if it is damaged?
Controlled by vagus nerve (receives signals from swallowing center)
If vagus nerve severed, local myenteric complex can maintain swallowing
Function of stomach
storage, mixing, and slow controlled emptying
HCl disinfects food, denature, and digests proteins and produces IF
Receptive relaxation
vagally mediated inhibition of fundic body tone which permits volume expansion of stomach and storage of food without a concomitant rise in intragastric pressure
Gastric motility (3 steps)
1) After eating, contractions start in mid stomach, slow wave frequency → push bolus toward antrum
2) Contractions become stronger and faster in antrum, outrun bolus → contents forced backward = Retropulsion (breaks up food into smaller particles and mix with digestive juices (chyme))
3) Transient opening of pylorus allows small particles and chyme to leave stomach and enter duodenum
Gastric emptying
things that effect gastric emptying
controlled by pyloric sphincter, normally under high tone
1) Distension
2) Type of food
3) Gastrin
4) Detection of food in duodenum
5) Cholecystokinin
How does distention of the stomach effect rate of emptying?
Rate of emptying increased by distension: increased stretch → increased peristalsis through vagal/myenteric reflexes → decreased pyloric tone
How does type of food effect rate of emptying?
Carbs leave stomach in a few hours, protein rich food leaves more slowly, and fat leaves the slowest
How does gastrin effect rate of emptying?
Gastrin: hormone secreted in presence of food in stomach
Stimulates peristaltic contraction and decreases pyloric tone
How does detection of food in the duodenum effect rate of emptying?
Detection of food in duodenum → reflex inhibition of gastric peristalsis and increase in pyloric tone
How does cholecystokinin effect rate of emptying?
Cholecystokinin: secreted by enteric endocrine cells in response to arrival of fats in duodenum → inhibit gastric motility
Vomiting
4 steps involved
Centrally regulated by vomiting center in brain
Steps involved:
1) Salivation (HCO3-) and sensation of nausea
2) Reverse peristalsis from upper small intestine to stomach
3) Abdominal muscles contract and UES and LES relax
4) Gastric contents are ejected
Migrating motility complex
sweep down gastric antrum and along small intestines between meals (every 90 minutes)
Housekeeping role = remove bacteria and indigestible material
Peristaltic wave begins in stomach → ileocecal sphincter → repeat
Wave initiated by motilin hormone released from small intestine
Eating terminates MMC
DO NOT HAPPEN IN LARGE INTESTINE
Phases of migrating motility complex (MMC) (3)
Phase I: quiescence, occurs 40-60% of 90 min duration
Phase II: motility increases but contractions are irregular
- Fails to propel luminal content
- Lasts 20-30% of MMC duration
Phase III: 5-10 minutes of intense contractions
-From body off stomach to pylorus to duodenum to ileocecal valve - (pylorus fully opens)
Small intestine motility
Segmentation: chyme mixed with digestive enzymes and continually exposes surface to new contents for absorption
Peristalsis: propels chyme 1 cm/min
Gastroileal reflex
stomach activity stimulates movement of chyme through the ileocecal sphincter
Ileocecal sphincter
normal?
opened by?
closed by?
normally closed (to prevent reflux of bacteria from colon into ileum)
Opened by distention of end of ileum (local reflex)
Closed by distension of proximal colon (local reflex)
Gastrocolic reflex
food in stomach stimulates mass movement in colon
Distension in ileum → ?
Distension in ileum → relaxation of ileocecal sphincter → contents pass into cecum of large intestine
Types of motility in the colon
Haustration
Mass movement
Haustrations
muscles of colon wall contracted intermittently to divide colon into functional segments known as haustra
Mass Movement
giant migrating contraction 1-3X/day
does forward propulsion
Intense and prolonged peristaltic contraction that strips an area of large intestine clear of contents
Segmental activity temporarily ceases, loss of haustration
Defecation
1) Mass movements push feces into rectum which is usually empty
* *Gastrocolic reflex stimulates this
2) Feces enter rectum → distension of rectum → stimulate defecation reflex
* *Spinal mediated via pelvic nerves
- Reflex relaxation of internal anal sphincter and voluntary relaxation of external anal sphincter → defecation
Acid secretion
HCl
Kills bacteria (disinfects food at pH 1.0)
Begins protein digestion - denatures proteins and activates pepsinogen → pepsin
Acid producing parietal cells also secrete IF when secreting acid
Mucosal Defenses in Stomach
mucus layer and alkaline (HCO3-) layer at cell surface (surface mucus cells) protects stomach lining
Prostaglandins can increase mucus production
Tight junctions between cells prevent acid from infiltrating layers of wall
Rapid turnover maintains surface integrity
Phases of gastric acid secretion (4)
1) Basal interdigestive phase
2) Cephalic phase
3) Gastric phase
4) Intestinal phase
Basal (interdigestive) phase of gastric acid secretion
follows circadian rhythm
Rate of acid secretion lowest in morning before awakening, highest in evening
Cephalic phase of gastric acid secretion
initiated by smell, sight, taste, and swallowing of food
Mediated by vagus nerve
Accounts for 30% of total acid secretion
Gastric phase of gastric acid secretion
stimulated by entry of food into stomach
Food distends gastric mucosa → activate vagovagal reflex and local ENS reflex
Partially digested proteins stimulate antral gastrin G-cell→release gastrin
Responsible for 50-60% of total acid secretion
Intestinal phase of gastric acid secretion
presence of amino acid and partially digested peptides in proximal portion of small intestine stimulates acid secretion
Stimulate duodenal gastrin G-cells → secrete gastrin
Accounts for 5-10% of total acid secretion
Stimulation of vagus nerve results in what effects on the cephalic phase of acid secretion (4)
1) ACh release
2) Histamine release from ECL cells
3) Release of gastrin-releasing peptide from vagal enteric neurons
4) Inhibition of somatostatin release from delta cells in stomach
Parietal cells
secrete HCl and Intrinsic Factor into stomach
Stimulation of parietal cells causes them to significantly increase their secreting surface area → prodigious HCl output
→ Luminal pH of 2
Have lots of mitochondria: use lots of ATP to pump H+ against big gradient
Acid secretion stimulation
acid secretion stimulated by ACh, Gastrin hormone, and pancreas substance histamine → increase in Ca2+ and cAMP in cell → activation of distinct protein kinases that phosphorylate and increase activity of H+/K+ ATPase
Effect of ACh on gastric acid secretion
from vagus nerve stimulation, binds muscarinic receptors on basolateral membrane → activate G-protein → increase [Ca2+] in cell
–> increase activity of H+/K+ ATPase in parietal cells
Effect of Gastrin on gastric acid secretion
bind gastrin receptors, also increases intracellular Ca2+
–> increase activity of H+/K+ ATPase in parietal cells
Effect of Histamine on gastric acid secretion
binds H2 receptors → activate G-protein → turn on AC → increase cAMP in cell
–> increase activity of H+/K+ ATPase in parietal cells
Direct pathway of acid secretion stimulation
ACh, gastrin, and histamine directly stimulate parietal cell, triggering secretion of H+ into lumen
Indirect pathway of acid secretion stimulation
ACh and gastrin stimulate histamine release from enterochromaffin-like cells (ECL) → histamine acts on parietal cell
H+/K+ ATPase and gastric acid secretion
H+ transported across apical membrane via H+/K+ ATPase
Primary active transport
Also drives Cl- and H2O movement into cell
Cl-/HCO3- anion exchanger and gastric acid secretion
HCO3- transported across basolateral membrane in exchange for Cl- via Cl-/HCO3- anion exchanger
Downhill movement of HCO3- drives Cl- into cell against gradient
When H+ transported out of cell → increase [HCO3-] in cell via CARBONIC ANHYDRASE activity
Secondary active transport
Cl- facilitated diffusion and gastric acid secretion
Cl- accumulation in cell due to Cl-/HCO3- exchanger, transported across apical membrane by Cl- facilitated diffusion = passive transport, CFTR channel
Cholera toxin → constitutively activate this channel
How does water travel in the stomach?
H2O follow HCl from blood into lumen via transcellular pathway
Alkaline tide
high pH of venous blood leaving stomach due to HCO3- transport
Protective barrier of gastric surface
Epithelial cells, mucous, and bicarbonate provide barrier to dissipation of massive pH gradient and harmful effect of acid
Mucous secreted by Goblet Cells and Mucous Neck Cells of the gland
- Mucous forms an unstirred gel layer in which H2O is trapped
- Serves as neutralization zone, so acid is neutralized
Carbohydrate absorption and digestion general rules
Only simple monomeric sugars can be absorbed!
Amylase is the major enzyme in saliva and pancreatic secretions
Other dietary sugars like sucrose and lactose can be digested at the surface of enterocyte
Plant starch amylopectin is largest single source of carbs in our diet
what types of nutrients are transported in the venules vs. lacteal vessel?
Venule → other nutrients (not fat) enter venule and portal vein
Central lymphatic lacteal vessel → products of fat digestion enter lacteal and blood stream at thoracic duct
Proteolytic enzymes from pancreas first secreted as what? why?
First secreted as inactive precursors (zymogens, proenzymes)
→ Prevent enzymes from digesting pancreatic membranes and each other before they are needed
In stomach: pepsinogen –> ?
In duodenum: trypsinogen –> ?
–> then goes on to do what?
In stomach: pepsinogen (proenzyme) → pepsin by stomach acid
In duodenum: trypsinogen → trypsin by brush border (microvillar) enzyme called enteropeptidase/enterokinase
*Trypsin → more active trypsin produced from trypsinogen and converts all other zymogens to active enzymes
Amylase
catalyzes hydrolysis of internal a-1,4 linkages, converts amylose and amylopectin → maltose, maltotriose, and a-limit dextrin
Free glucose is NEVER the product of amylase digestion
Cellulose = B-1,4 linked polymer → cannot be digested = “fiber”
Mucosal Sucrase-Isomaltase (SI)
last stage of small intestinal digestion of branch points of starch to glucose, breaks 1,6 linkages
Convert a-limit dextran → glucose
Mucosal Maltase-Glucoamylase (MGA)
inal step in small intestinal digestion of linear forms of starch to glucose
Convert maltotriose → glucose
Sucrase
converts sucrose → glucose and fructose
Trehalase
converts trehalose → glucose
Lactase enzyme deficiency
lactose intolerance due to deficiency of lactase enzyme that converts lactose to glucose and galactose
Absence of brush border enzyme lactase
Unabsorbed lactose draws water into intestinal lumen → osmotic diarrhea
Gut bacteria flora metabolize unabsorbed lactose → gases
Carbohydrate uptake
intestinal sugar transportes transport monosaccharides (glucose, galactose, and fructose) from intestinal lumen to blood
Na+-Dependent Glucose Transporter (SGLT1)
brush border/apical membrane of enterocytes, transports glucose and galactose with Na+ from lumen → cytosol
Requires sodium as a co-transporter
Genetic absence of SGLT1 → ?
glucose-galactose malabsorption → diarrhea upon sugar ingestion due to reduced small intestine Na+ fluid absorption and fluid secretion secondary to osmotic effect of non-absorbed monosaccharide
Potentially fatal
Na+-Independent Fructose Transporter (GLUT5)
apical transporter, transports fructose from lumen into cytosol
Na+-Independent Fructose Transporter (GLU2)
basolateral and transports all three monosaccharides from cytosol to blood
Protein digestion: begins in ______ where what happens?
ends where?
begins in stomach - Pepsin breaks down 15% of proteins to small peptides
ends in small intestine
Small intestine in digestion of proteins
pancreatic proteases like trypsin, chymotrypsin, carboxypeptidase and elastase break down proteins to oligopeptides di/tri peptides and amino acids
Endopeptidases vs. Exopeptidases
Endopeptidases: secreted, hydrolyze interior peptide bonds
Exopeptidases: secreted, hydrolyze one AA at a time from carboxy (C)-terminus of proteins and peptides
Endopeptidases include…(3 examples)
Trypsin
Chymotrypsin
Elastase
*all secreted as zymogens
Exopeptidases (2 examples)
Carboxypeptidases A and B (secreted as zymogen, Pro-Carboxypeptidase A and B)
Brush border proteases (3)
function?
peptidases break down oligopeptides into amino acids, dipeptides, and tripeptides
1) Aminopeptidase
2) Dipeptidyl aminopeptidase
3) Dipeptidase
Intracellular peptidases
peptidases in enterocyte can break down di/tri peptides into amino acids
Steps of small intestine protein digestion (5)
1) Activation of trypsinogen→ trypsin by brush border enterokinase
2) Activation of all other precursors by trypsin
3) Trypsin, chymotrypsin, elastase, carboxypeptidase A and B, all hydrolyze protein to amino acids and di-, tri-, and oligopeptides
4) Brush border proteases hydrolyze oligopeptides to amino acids
5) Pancreatic proteases digest themselves and each other
four mechanisms of protein uptake
1) Na+-dependent cotransport
2) Sodium independent transporters of amino acids
3) Specific carriers for small peptides (di/tri) linked to H+ uptake (cotransporter)
4) Pinocytosis of small peptides by enterocytes (infants)
Na+-dependent cotransport
di and tripeptides are absorbed intact
Cotransporters utilize the N+/K+ ATPase gradient are major route for different classes of amino acids, water follows
Broken down into AAs by cytoplasmic peptidases in the enterocyte
AAs exit basolateral membrane of enterocyte by facilitated diffusion and enter blood capillaries
Bile acids
Primary bile acids are produced in the liver from cholesterol
Secondary bile acids are formed by bacteria in the intestine and colon
Bile acids are complexed with glycine or taurine to make bile salts
Bile is recycled during a meal by uptake in distal ileum = enterohepatic circulation
Pancreatic lipase
Converts triglyceride (unabsorbable) into a 2-monoglyceride and two free fatty acids (absorbable)
Fat droplets emulsified by bile salts and lecithin to form 1 um particles → increase surface area for digestion by lipase and colipase
Pancreatic colipase
protein that anchors lipase to surface of droplets
Pancreatic Micelles
products of lipase digestion (2’-monoglycerides and fatty acids) are solubilized in bile-salt micelles
Cylindrical structure, hydrophilic groups pointing out, hydrophobic part inward
Required to transport products of fat digestion through “unstirred” water layer near surface of enterocytes
Steps of lipid movement across enterocyte into lacteal
7 steps
1) products of lipase digestion (2’ monoglycerides and fatty acids) solubilized in bile salt micelles
2) Bile salt micelles allow transport through “unstirred water”
3) When lipids strike cell surface → diffuse passively into enterocyte
4) → packaged into chylomicrons (triglycerides, phospholipids, cholesterol, apolipoproteins)
5) → incorporated into secretory vesicles in golgi
6) → vesicles migrate to basolateral membrane and released into interstitial space by exocytosis
7) → enter lacteals (too large for capillaries)
Fat soluble vitamin absorption
(A, D, E, K): absorbed same as fat and cholesterol
Steatorrhea
excessive loss of fat in stool as well as lipid soluble vitamins
Absorption of water-soluble vitamins
B vitamins, C vitamins, Niacin, Folic acid, Pantothenic acid, and Biotin
Absorbed by cotransport with Na+ or by passive diffusion
Absorption complete in upper small intestine except for B12
Absorption of B12 (cobalamin)
4 steps
B12 absorption in distal ileum in complex with IF
Dietary proteins contain B12 (cobalamin) - important for RBC production
1) B12 binds salivary R protein in stomach
2) Pancreatic proteases remove R protein in duodenum
3) IF from stomach then binds B12 in duodenum
4) IF/B12 complex binds specific B12-IF receptor in terminal ileum enterocyte membrane
Impairment of B12 absorption → pernicious anemia
Water absorption in jejunum
absorption of sugars and amino acids in cotransport with Na+ causes Cl- to follow, and H2O to follow for osmotic reasons = PARACELLULAR pathway
Osmotic gradient due to solute deposition in confined regions between cells → driving force for H2O absorption
Crypts vs. Villi with water reabsorption:
Crypts = net fluid secretion from cells
Villi: net fluid absorption, vill surface area > crypt surface area
Ileum and water absorption
most nutrients already absorbed → continues to absorb H2O
Cl- absorbed by TRANSCELLULAR pathway involving Cl-/HCO3- exchange in apical membrane and facilitated diffusion across basolateral membrane
Colon and water reabsorption
Na absorption via apical Na+ channels (epithelial sodium channel, ENaC)
Aldosterone promotes ENaC water reabsorption and K+ secretion
Potassium Absorption
passive process
Paracellular movement in jejunum (due to low [K+] in intercellular space from Na+/K+ ATPase) but transcellular in colon
In severe diarrhea, when fluid loss is substantial, can cause hypokalemia
-Give K+ with oral rehydration fluids
Calcium and Magnesium absorption
Ca2+ and Mg2+ compete for uptake by cells - ONE OR THE OTHER
Ca2+ enters enterocyte passively down its electrochemical gradient in proximal intestines
Uptake of Ca2+ in intracellular calcium stores maintains the gradient
Ca2+ ATPase pumps calcium out to the blood
Vitamin D absorption
And effect on Calcium absorption
- synthesized in skin, or absorbed by intestine
- 25-hydroxylated in liver
- 25-OH VitD is 1-hydroxylated in kidney in presence of PTH
- VitD binds to cytoplasmic receptor, activating transcription/translation
**VitD stimulates uptake if Ca2+ by increasing Ca2+ binding proteins and Ca2+ ATPase molecules
Iron absorption
regulated absorption in proximal intestines
Transported across apical membranes as either heme or Fe2+ (Receptor mediated)
Two possible fates:
1) Binds apoferritin → ferritin stays in cell and is lost when cell dies
2) Binds transferrin (carrier protein) → leaves cell and goes into blood
Osmotic diarrhea
caused by impaired digestion or defects in absorption
Causes: Lactase deficiency, ileal resection (bile salts not absorbed), Celiac disease (gluten sensitivity with gliadin-induced destruction of villi)
Secretory diarrhea
may be caused by vibrio cholerae
Increases cAMP levels in cells and activates CFTR chloride channel → water into lumen
What effect will Loperamide have on secretory diarrhea caused by cholera?
Loperamide will have NO impact on someone who has cholera induced diarrhea
Oral rehydration
antibiotics plus KHCO3 to prevent hypokalemia and metabolic acidosis, glucose or amino acids with NaCl to facilitate the absorption of electrolytes and water
Oropharynx function:
Teeth + lips → ?
Mastication, saliva → ?
Tongue → ?
Pharynx →
Teeth + lips → biting and grinding
Mastication, saliva → conversion of bite into small, soft, lubricated bolus
Tongue → push bolus into pharynx
Pharynx → move bolus from mouth to upper esophagus
Function of esophagus (3)
Transport: conduit for food and water from oropharynx to stomach
Barrier: protection of mediastinum and lungs from ingested food/water
1-way system → prevent reflux of gastric contents into pharynx or airway
Esophageal Motility disorders
typical presenting symptoms (2)
diagnosis (2)
Symptoms:
**dysphagia to BOTH solids/liquids
chest pain
DX:
Exclude structural lesion (upper endoscopy, barium esophagram)
Esophageal manometry
Structural Esophageal disorders
typical presenting symptoms (3)
luminal narrowing/obstruction
Symptoms: Dysphagia to solids → liquids much later, Weight loss, heartburn
Diseases of esophageal motility (3)
1) Achalasia: abnormal peristalsis, failure of LES relaxation
2) Spastic disorders of esophagus
3) Scleroderma (weak peristalsis)
Diseases of esophageal structure (4)
1) Esophageal strictures
2) Extrinsic compression
3) Eosinophilic Esophagitis (EoE)
4) Esophageal rings
Gastroesophageal reflux disease (GERD)
Pathophysiology
pathologic reflux of gastric juice (acid) into esophagus due to reduced LES tone
Acid in esophagus or airway → symptoms and/or esophageal damage
Esophagus lacks defenses (mucous secretion, alkalinity) against acid
Causes and risk factors of GERD
Inappropriate LES relaxation
**hiatal hernia
Risk factors: alcohol, tobacco, pregnancy, obesity, fat-rich diet
Rare: Zollinger-Ellison, Sjogren’s, Scleroderma
Symptoms of GERD (4)
- *Heartburn: burning sensation, substernal or epigastric, rises in chest
- May be positional (lying down)
- Often postprandial (After meals)
**Regurgitation with acidic taste
Cough, throat clearing, hoarseness
Damage to enamel of teeth
Treatment of GERD (2)
antacids, anti-secretory medications (PPI)
Complications of GERD (2)
Barrett’s esophagus, ulceration with stricture
Diagnosis of GERD (4)
usually by symptoms
response to acid suppressive therapy (PPIs)
Endoscopy: usually for refractory symptoms
**Vast majority normal
-Ambulatory pH testing
Transnasal catheter or wireless capsule
Achalasia
cardinal motility disorder of esophagus
Causes of Achalasia (5)
damage to myenteric plexus ganglion cells (between inner circular and outer longitudinal muscle of the muscularis propria layer)
1) Idiopathic - affects both genders, all races, adults - VAST MAJORITY
2) Pseudoachalasia (secondary achalasia)
- Direct mechanical obstruction of LES
- Infiltrative submucosal invasion
- Paraneoplastic → ab to myenteric plexus
* *Chagas disease
Pathophysiology of Achalasia
1) Impaired relaxation of lower esophageal sphincter
- Due to selective loss of inhibitory neurons in myenteric plexus → unopposed excitatory (ACh) neurons → hypertensive, non relaxed esophageal sphincter
2) Absence of normal peristalsis in distal esophagus
Symptoms of achalasia (7)
**Dysphagia to solids AND liquids
Weight loss Regurgitation Chest pain Difficulty belching Heartburn Hiccups
Diagnostic testing for achalasia
Esophageal manometry
Barium swallow study (“bird beak sign” due to buildup and distention of esophagus)
Treatment of achalasia
Medical therapy (3) Endoscopic therapy (3) Surgical therapy (1)
Medical therapy:
1) Nitrates (stimulate intracellular Ca2+ → SMC relaxation)
2) Ca2+ channel blockers
3) Sildenafil
Endoscopic therapy:
1) GE junction botulinum toxin injections → inhibit ACh release from nerve endings
2) Pneumatic balloon dilation → tear LES muscle fibers
3) POEM: Per-Oral Endoscopic myotomy
Surgical: Surgical Myotomy
Barrett’s Esophagus - what is the histological change?
metaplasia of lower esophageal mucosa from stratified squamous epithelium → nonciliated columnar epithelium with goblet cells
Barrett’s Esophagus
Consequence of GERD, response of lower esophageal stem cells to acidic stress
Significant risk of developing dysplasia to esophageal adenocarcinoma
Endoscopy with biopsies every 3-5 years to assess for dysplasia
Dysplasia → much greater risk for esophageal cancer development
Treatment of Barrett’s Esophagus (2)
Esophagectomy
Endoscopic treatment for HGD and early esophageal adenocarcinomas
- Ablation of Barrett’s tissue
- Endoscopic resection of lesions
Esophageal Adenocarcinoma
- malignant proliferation of what?
- Risk factors? (7)
- Most common where?
malignant proliferation of glands in LOWER ⅓ of esophagus
Risk factors: old age, smoking, obesity, GERD, BARRETT’S ESOPHAGUS, radiation exposure
-More common in men
Rising incidence in US and Europe - most common type in West
Squamous cell esophageal cancer
- malignant proliferation of what?
- Risk factors? (8)
- Most common where?
squamous cell epithelial malignancy in UPPER or MIDDLE third of esophagus
Risk factors = IRRITATION:
- Old age, alcohol/tobacco use, hot tea, achalasia (rotting food in esophagus), esophageal web (traps rotting food), esophageal injury (e.g. lye ingestion)
- More common in men and african americans
Declining incidence in US/Europe, more common worldwide
Symptoms of esophageal cancer
weight loss, hemoptysis, chest pain, anemia
Progressive dysphagia to solids → liquids
Does not cause sx until advanced
Esophageal strictures
cardinal symptoms
benign or malignant
Cardinal symptom = dysphagia to solids
-Painless, symptoms on regular/daily basis, progressive, weight loss
Causes of
Benign esophageal strictures
Malignant esophageal strictures
GERD, radiation, caustic ingestion, congenital
*Rule out cancer with biopsy during EGD
Malignant: squamous cell carcinoma, adenocarcinoma
Eosinophilic Esophagitis (EoE)
Chronic immune/antigen mediated esophageal disease
Diagnosis:
- Symptoms of esophageal dysfunction and dysphagia
- Vomiting, pain, dyspepsia, progressing to odynophagia and stenosis
- Eosinophilic infiltrate in esophagus
- Absence of other potential causes of esophageal eosinophilia
- Can cause esophageal strictures → ringed appearance
Demographics of Eosinophilic Esophagitis (EoE)
Most common less than 40 years of age
White males classic
Commonly associated with other allergic diseases (asthma, atopic dermatitis, seasonal allergies, food allergies)
Treatment of Eosinophilic Esophagitis (3)
3 D’s
Drugs: steroids (topical»_space;> systemic), swallowed topical steroids
Diet: elemental diet (allergen-free)
Dilation
Diagnosis of oropharyngeal disease
History, physical exam = MOST helpful
Barium swallow
Barium swallow
xray video of mouth and throat under direct observation while patient chews and swallows various consistencies of radio-opaque barium
Causes of esophagitis
inflammation and injury to esophageal mucosa
1) Chemical injury:
- Reflux of gastric contents** most common
- Acids, alkalis, alcohol, tobacco
2) Medications
3) Infection:
- Fungal (Candida) → white plaques
- Viral (HSV, CMV, adenovirus) → punched out ulcers, viral inclusions
4) Immune related:
- Eosinophilic esophagitis
- Dermatologic diseases (lichen planus)
5) Radiation, trauma
6) Graft-versus-host disease
Reflux esophagitis
2 clinical features
what happens if left untreated?
Clinical features: heartburn and regurgitation
If left untreated → severe ulcerations, strictures, Barrett’s esophagus, and adenocarcinoma may develop
Causes of reflux esophagitis
transient LES relaxation decreased LES tone hiatal hernia increased intraabdominal pressure delayed gastric emptying
Sequence following GERD all the way to cancer
GERD-Barrett Esophagus (metaplasia)-Dysplasia-Esophageal Adenocarcinoma
Zenker’s diverticulum
outpouching of pharyngeal mucosa through an acquired defect in muscular wall (false diverticulum)
Uppermost esophagus, above esophageal sphincter
Regurgitation, halitosis, and aspiration
Associated with reduced UES compliance
Esophageal webs
protrusion of esophageal mucosa
Often in UPPER esophagus
Presents with dysphagia for poorly chewed food
Increased risk for esophageal squamous cell carcinoma
Esophageal Varices
Dilated submucosal veins in LOWER esophagus
Due to PORTAL HTN and shunting of blood from portal to system venous system
Left gastric vein backs up into esophageal vein
Presentation: PAINLESS hematemesis
Associated with cirrhosis - most common cause of death in cirrhosis
Mallory-Weiss Syndrome
Longitudinal laceration of mucosa at gastroesophageal junction
Caused by vomiting usually due to alcoholism of bulimia
Presents with PAINFUL hematemesis
Tracheoesophageal Fistula
most common variant
presentation
congenital defect resulting in a connection between the esophagus and trachea
Most common variant = proximal esophageal atresia with distal esophagus arising from trachea
Presents with vomiting, polyhydramnios (baby can’t swallow amniotic fluid), abdominal distension (breathing into stomach), and aspiration
Congenital esophageal stenosis
Anomaly demonstrates significant narrowing of mid-esophagus
→ Esophageal web/rings, muscular hypertrophy, inflammation
Cardia contains what cell type and secretes what?
Gastric pits contain mucous cells that secrete mucus and small amount of pepsinogen
Fundus contains what gland type? (cells in this gland?)
Contain gastric pits with OXYNTIC glands = mucous cells, parietal cells, chief cells, endocrine cells, and enterochromaffin cells
Antrum contains what gland type? (cells in this gland?)
Contains PYLORIC glands = mucous cells, endocrine cells, G cells (produce gastrin), and D cells (produce somatostatin)
Stomach function
1) Receptive relaxation
2) Digestion/mixing
3) Slow release of chyme into duodenum
4) Parietal cells secrete HCl to disinfect food, and IF for B12 absorption
Movement of liquids and solids in stomach
Liquids rapidly emptied from proximal stomach to duodenum
Solids initially stored in proximal stomach and then move to antrum
- -> Vagally mediated segmented contractions originating in mid-body of greater curve mix food
- -> When food particles 1 mm or less, it empties into pylorus
Inhibitory mechanisms in small intestine prevent it from being overwhelmed by rapid entry of nutrients from stomach
-CCK, secretin, GIP, pH receptors, osmoreceptors, etc. in duodenum reflexively inhibit gastric emptying
Mucosal protective factors that prevent self-destruction
Prostaglandin E2 and Prostacyclin → stimulate bicarb secretion, mucus, and mucosal blood flow
H. Pylori Gastritis:
Epidemiology
most common cause of gastritis, typically in ANTRUM
- adult prevalence of H. pylori correlates with crowded living conditions and socioeconomic status during childhood
- Transmission occurs person-to-person, especially among children - fecal-oral and environmental spread
H. pylori bacteria
gram-negative spiral
produces abundant urease which produces ammonia and raises local pH
→ escape acidic gastric juice and burrow through mucus layer to colonize surface epithelium of gastric mucosa
Elicits robust inflammatory response → active/chronic gastritis
Virulence factors of H. Pylori (6)
1) Flagella to maneuver through gastric mucous
2) Adhesion molecules bind to gastric foveolar cells
3) Acid resistance with urease
4) CagA protein: decreased cell adhesion-associated with both gastric and duodenal ulcers and cancer
5) VacA: exotoxin → pores in membrane
6) Minimization and evasion of immune response
H. Pylori mucosal biopsy reveals what?
Mucosal biopsies indicate presence of urease (CLO) - use pH sensitive test medium
Shows infiltration of gastric mucosa with neutrophils (active gastritis) or lymphocytes (chronic gastritis)
diagnosis of H. pyloris infection
1) Mucosal biopsy
2) Culture (least sensitive)
3) Blood antibody test
4) Urea breath test
5) Stool antigen test
Blood antibody test for H. Pylori
H. pylori produces circulating antibody that can be detected on ELISA - BUT can’t be used acutely to determine effect of abx
Urea breath test
urea radiolabeled ingested with liquid meal, if urease present, can be detected by analysis of expired breath
Virtually 100% PPV and 95% NPV
PPI can result in false negative test
Stool antigen test
similar performance characteristics of UBT, most commonly used test in outpatient setting to confirm eradication
Spectrum of disease with an H. Pylori gastritis infection
Asymptomatic
Gastritis
Peptic ulcer disease - both duodenal and gastric ulcers
Neoplasia (gastric cancer, lymphoma)
Treatment of H. pylori Infection
course for 7-14 days
Triple therapy: Proton pump inhibitor + Amoxicillin + Clarithromycin
Quadruple therapy = PPI + bismuth + tetracycline + metronidazole
Confirm eradication (stool antigen)
Diseases associated with H. Pylori
Gastritis, gastritic and duodenal ulcers, gastric adenocarcinoma, gastric lymphoma
Eosinophilic gastritis
- infiltration of gastric wall with eosinophils
- Allergic disease (e.g. cow’s milk) and parasitic infection
Symptoms: delayed gastric emptying, associated peripheral eosinophilia
TX: corticosteroids, surgery
Granulomatous gastropathy
Associated with Crohn’s, sarcoidosis, and infection
Autoimmune Gastritis
**CD4+ T cells against parietal cells
Anti-parietal cell and anti-Intrinsic Factor antibodies
+/- pernicious anemia
Most common in scandinavian / N. Euro descent
Can develop intestinal metaplasia → higher risk of gastric cancer
Histology: lymphocyte and plasma cell infiltrate in the body of stomach and glandular atrophy
Gastropathy
gastroduodenal injury with little or no inflammation associated with lesion
NSAID-Induced Injury:
cause
risk factors
treatment
Gastropathy
Cause: prostaglandin depletion
Increased risk: elderly, prior ulcer disease
Treatment: PPIs - healing usually occurs even if NSAID is continued
Ulceration vs. erosion
Ulceration = > 5mm in diameter, depth breaches muscularis mucosa
- Often gastric ulcers but can also be in duodenum
- Increased risk for GI bleed
Erosion = not below mucosa
Ethanol-Induced Injury
lesion similar to NSAID induced lesions, can occasionally cause serious bleeding, but rare
Stress related mucosal injury
hemorrhages and erosions of stomach and duodenum in patients under “physiologic stress”
Morphologically resembles acute gastritis
Patients with CNS injury, prolonged mechanical ventilation, coagulopathy, and burns - NOT pts in coronary care units
What kind of ulcers?
Trauma, shock, sepsis → ?
Burns → ?
Intracranial disease → ?
Trauma, shock, sepsis → stress ulcers
Burns → Curling’s ulcers
-Due to hypovolemia and decreased blood supply
Intracranial disease → Cushing ulcers
-Increased ICP → increased vagal stimulation → increase ACh → increased acid production by parietal cell
Pathogenesis of stress related mucosal injury
most patients not acid hypersecreters but due to mucosal ischemia/vasoconstriction
Peptic ulcer disease
acid mediated ulceration of distal stomach or proximal duodenum
Pathogenesis of peptic ulcer disease
gastroduodenal mucosal defenses unable to protect epithelium from corrosive effects of acid and proteases (pepsin)
Primarily disease of failed mucosal integrity, NOT excess acid/pepsin secretion
Predisposing factors for gastric ulcer vs. duodenal ulcer
gastric ulcer: H pylori infection, NSAID use
duodenal ulcer: H. pylori and ZE syndrome
Symptoms of peptic ulcer disease
Asymptomatic, or burning epigastric pain relieved by food or antacids, may awaken patient from sleep
“Nocturnal pain relieved with antacids” = most specific sxs
Complications of peptic ulcer disease (3)
Bleeding (15%)
Perforations/Penetration (5%) → acute development of peritonitis
Obstruction (2%) → nausea, vomiting, early satiety
Due to repeated ulceration and formation of scar tissue
Treatment of peptic ulcer disease
PPI and H.pylori eradication are cornerstones of therapy
Severe acute bleeds → PPI drips used in ICU to tightly control pH
Systemic presentation of gastric carcinoma (5)
1) Acanthosis nigricans
2) Leser-Trelat sign (seborrheic keratoses)
3) Spread to left supraclavicular node (Virchow’s node)
Distant mets:
4) Sister Mary Joseph nodule: periumbilical region (intestinal type)
5) Bilateral ovary mets = Krukenberg tumor (diffuse type)
Gastric Adenocarcinoma types (2)
1) diffuse type
2) intestinal type
Diffuse type
signet ring cells, diffusely infiltrate gastric wall
Can cause desmoplasia = thickening of stomach wall (linitis plastica)
Intestinal type
large, irregular ulcer with heaped up margins
Most common in lesser curvature of antrum
Associated with H. pylori, autoimmune gastritis, nitrosamines (smoked food, Japan), blood type A
Epidemiology of gastric adenocarcinoma
90% of all malignant gastric tumors
2nd most common malignancy in the world (but not USE)
Prognosis of gastric adenocarcinoma
related to depth of invasion (worse if in muscular layer)
High mortality unless disease detected early
5-year survival = 30% (90% for early cancer)
Symptoms of gastric adenocarcinoma
early vs. late
Early: dyspepsia, dysphagia, nausea
Late: weight loss, anorexia, early satiety, anemia
Genetics in gastric adenocarcinoma (3)
1) Wnt signalling pathway activation (can occur with loss of APC as in FAP)
2) Loss of CDH1 (mutation or methylation)
- Common in diffuse type cancers
3) Amplification of Her2/neu
→ TX with trastuzumab (TKI)
3 gastric polyp types
1) Hyperplastic polyps
2) Gastric adenomas
3) Fundic gland polyps
Hyperplastic polyps
proliferation of gastric foveolar cells (mucus producing)
Arise from chronic inflammation
Found in gastric body autoimmune gastritis and H. pylori infection with chronic atrophic gastritis
*Rare malignant potential
> 1 cm → increased risk of dysplasia or adenocarcinoma
Histology of hyperplastic polyps
Histology: inflammation and edema, cystically dilated foveolae
typically in antrum of stomach
Gastric adenomas
arise from dysplastic epithelial cells, risk progression to adenocarcinoma
Premalignant - Should be removed endoscopically
Familial adenomatous polyposis (FAP) → multiple polyps and adenomas
Histology of gastric adenomas
dark, atypical cells
Fundic gland polyps
dilated oxyntic glands lined by flattened parietal and mucous cells (most common type of gastric polyp)
Unrelated to H. pylori infection
Typically due to PPI use
Benign - No malignant potential
Increased incidence with FAP
Histology of fundic gland polyps
cystically dilated oxyntic gland
Stromal Tumors
benign gastric tumors arising from supporting tissues
Leiomyomas and Lipomas → malignant leiomyosarcoma, liposarcoma
Usually asymptomatic, but larger ones can present with abdominal pain and GI bleeding
TX = surgical resection
Gastrointestinal stromal tumors (GISTS)
subtype of stromal tumor
Express c-KIT (CD117) transmembrane receptor tyrosine kinase → TX with imatinib (receptor tyrosine kinase inhibitor) and surgical resection
Mesenchymal neoplasms derived from interstitial cells of Cajal (pacemaker cells)
Neuroendocrine Tumors: Carcinoid tumors
arise from enterochromaffin or enterochromaffin-like cells in intestinal tract
Well-differentiated endocrine neoplasm
Can be associated with MEN1
Histology: Nests and trabeculae of monomorphic cells
Sporadic type → higher rate of malignant behavior
Atrophy associated → typically indolent
Gastric Lymphoma
Strong association between H. pylori infection and primary gastric B-cell lymphoma
Low grade clonal proliferation of B-cells in H. pylori induced gastric MALT → lesion may progress to high-grade lymphoma → require surgical resection and chemo/radiation
Hypertrophic Pyloric Stenosis
hyperplasia of pyloric muscularis propria → obstructs gastric outflow
Presents in 2-3rd week of life with regurgitation and persistent projectile, nonbilious vomiting (DEVELOPS AFTER YOU ARE BORN)
More common in boys
Presents as firm ovoid abdominal mass
TX: surgical splitting of muscularis propria (“myotomy”)
Menetrier disease
very rare
Mucous cell hyperplasia
Gastric acid secretion low-normal
Signs/symptoms: abdominal pain, weight loss, N/V, hypoalbuminemia
Zollinger-Ellison Syndrome
neuroendocrine tumor in pancreas or duodenum
Gastrin secreted leading to hyperplasia of parietal cells
Signs/symptoms: chronic diarrhea, abdominal pain, peptic ulcers
4 Layers of GI tract
- mucosa
- submucods
- muscularis externa
- Serosa adventitia
Mucosa
epithelial layer + lamina propria (underlying loose, vascularized CT) + muscularis mucosae (thin layer of smooth muscle underlying this)
Cells in Epithelial layer
contains enteroendocrine cells (secrete into blood) and M cells (immune sampling cells)
Contain IgA receptor that are ingested and transported into lumen → first defense layer
Basal lamina
underlying epithelial cells, specialized to allow molecules across epithelium of gut
Lamina propria
contains capillaries and WBCs (including MALT)
Lymphocytes, plasma cells, and macrophages scattered throughout lamina propria
Submucosa
connective tissue (more dense than mucosa), larger blood vessels, nerve plexes, glands, lymphatic nodules
Nerve plexus within submucosa
Meissner’s nerve plexus
2 divisions of muscularis externa
inner circular and outer longitudinal smooth muscle layers
Function of muscularis externa
Peristalsis and churning of lumenal contents
Nerve plexus within muscularis externa
Auerbach’s plexus between inner circular and outer longitudinal smooth muscle
Layers of stomach
- inner circular
- outer longitudinal
- oblique smooth muscle (churning)
Serosa/adventitia
outer covering of squamous epithelial cells separated from underlying muscular layer by thin CT layer
- Adventitia = above diaphragm (esophagus), no outer squamous layer
- Contains large blood vessels and nerves
How do we avoid digesting ourselves?
- Mucosae lining the tube creates a microenvironment at surface of the tube that is resistant to proteolytic digestion
- Mucin = heavily glycosylated, heavily hydrated, resistant to proteolysis → prevent digestion and protective layer from bacteria
Prevention of bacterial infection along the GI tract
Lymphoid tissue present as scattered individual cells and as lymphatic nodules
Peyer’s patch: group of lymphatic nodules
M-cells: specialized epithelial cells, function in antigen-uptake
- Phagocytose luminal contents and present antigens to underlying lymphocytes and macrophages
Plasma cells in nodules release IgA immunoglobulins that bind to receptors on epithelial cells and are transcytosed to lumenal surface → antibacterial agents
Prevents pathogenic colonization and adherence
Neural control of GI tract (2)
1) Enteric neurons: lie outside CNS, produce local gut motility
2) Parasympathetic and sympathetic fibers: directed by CNS, enables coordinated input → coordinated peristalsis and effects on blood vessels (PS) and glands (S)
Function of esophagus
convey ingested material from pharynx to stomach (no digestion)
Location of pancreas
posterior to stomach, anterior to thoracic spine/ribs in retroperitoneum
Blood supply of pancreas
superior pancreaticoduodenal and splenic arteries (branch off celiac axis) and inferior pancreaticoduodenal artery (branch off the SMA)
Exocrine function of the pancreas
made up primarily of what two types of cells?
3 major functions
made up of epithelial cells with acinar glands (Acinar cells)
1) Secrete digestive enzymes as pro-enzymes/zymogens and amylase/lipase as active enzymes in response to cholecystokinin
2) Produce large amounts of bicarb and water in response to secretin→ maintain flow throughout ducts, keep zymogens inactive with low pH, protect pancreas and duodenum/ileum from low pH
3) Trypsin inhibitor in pancreas deactivates any trypsin prematurely activated
Pathway of pancreatic excretions
enzymes secreted across apical cell membrane into tiny ductule at center of each acinus
→ ductules coalesce into larger exocrine duct system of pancreas
→ main (ventral) duct and ampulla of Vater
Endocrine function of the pancreas
pancreatic islet cells produce insulin, somatostatin, VIP, glucagon, and others
Acute pancreatitis
when pancreatic enzymes are inappropriately and prematurely activated resulting in autolysis of the gland → severe inflammation and necrosis of pancreatic tissue
Labs used for diagnosis of acute pancreatitis
serum amylase and lipase elevated > 3x upper limit of normal
Lipase more specific for pancreatitis - rises within 1-2 hrs, remains high for 1 week
Amylase - rises and falls within 24-48 hrs - can be high due to other etiologies (mumps, Sjogrens, penetrating peptic ulcer, ectopic pregnancy, intestinal ischemia/trauma, etc.)
Imaging used for diagnosis of acute pancreatitis (what are the benefits of each?)
contrast CT or ultrasound
US: best for gallbladder stones
CT: detects edema, calcifications, fluid collections (complications of acute pancreatitis)
Pathophysiology of acute pancreatitis
caused by obstruction of pancreatic duct → stagnation of pancreas enzymes within duct lumen and activation of enzyme cascade
Lipase released from dying acinar cells → break down fats → fatty acids precipitate with calcium and form insoluble soaps
→ Coagulation necrosis of gland and hemorrhage into retroperitoneum
→ Intense infiltrates of neutrophils and apoptosis of epithelial cells
Main causes of acute pancreatitis
1) Gallstone: most common cause of pancreatitis in US**
2) Ethanol
3) Other causes: tumors, surgical, congenital ductal abnormalities, Sphincter of Oddi dysfunction types 2 and 3, hyperlipidemia, blunt/penetrating trauma, drugs, hypercalcemia, infection, CF
How does ethanol cause acute pancreatitis?
direct toxic effect on pancreatic acinar cells and ductal epithelium → premature release/activation of trypsinogen and stagnant flow of pancreas juice
How do gallstones cause acute pancreatitis?
Stone lodges in distal common bile and/or ampulla → obstructing ventral duct and causing bile reflux into pancreas → zymogen activation
Symptoms of acute pancreatitis
1) sudden onset severe pain in upper abdomen, radiating to back
2) Nausea/vomiting
3) Low grade fevers
* Self-limited
Elevated pancreatic enzymes in serum
Treatment of acute pancreatitis (4)
1) admission, NPO, IV pain meds, IV fluids, time - supportive only usually
2) Consider ERCP for bile duct stone removal
- If persistent bile duct stone → requires extraction
3) Cholecystectomy to remove source of stones in some cases
4) Avoidance of alcohol is KEY
Complications of acute pancreatitis (5)
1) Ileus (paralysis of gut)
2) Intra-abdominal hemorrhage (digestion through artery)
3) Pseudocyst formation
4) Severe pancreatitis → bowel/bile duct obstruction, shock, respiratory distress/failure/renal failure, death
5) Pancreatic necrosis → increases mortality significantly
Chronic Pancreatitis
develops after repeated bouts of acute pancreatitis, permanent destruction of pancreatic parenchyma with replacement by fibrosis
Main features of chronic pancreatitis (4)
1) Ductal strictures/stones → pain, exocrine failure
- NOT seen in acute pancreatitis **
2) Pancreatic pseudocysts → pain, nausea, vomiting
3) Acinar destruction → exocrine failure
4) Diabetes → endocrine failure (late)
Diagnosis of chronic pancreatitis (7)
1) History and physical
2) Plan abd xray
3) CT
4) Endoscopic US
5) Rapid fat stool stain
6) 72 hour quantitative stool collection
7) Secretin stimulation test
What does a CT of chronic pancreatitis show?
CT → dilated duct, atrophy, calcifications, pseudocysts
Mainstay of diagnosis
What is the secretin stimulation test?
what is required for diagnosis of chronic pancreatitis?
tube in stomach and duodenum - duodenal bicarb response to secretin [HCO3-] less that 80 mEq/L after 2 hours = diagnostic of pancreatic exocrine failure
-Secretin should stimulate bicarb and water secretion from pancreas in normal patient
Causes of chronic pancreatitis
typically chronic alcohol abuse +/- smoking
ALCOHOL = most common cause
Genetic conditions: CF, mutations in trypsinogen (PRSS), or trypsin inhibitor genes (SPINK), familial hypertriglyceridemia
Pathophysiology of chronic pancreatitis
Replacement of healthy pancreatic tissue by hard, fibrous tissue, and possible atrophy of the gland
Pancreas juice becomes viscous and calcifications develop within duct
Fibrous tissue → strictures of duct
Microscopic appearance of chronic pancreatitis
broad bands of scar tissue replace lost tubular tissue
Moderate numbers of lymphocytes/plasma cells present
Relative sparing of islet cells
Symptoms of chronic pancreatitis (3)
1) Malabsorption
2) Pain (chronic, waxes/wanes, never disappears) - epigastric, radiates to back, worse after meals
3) Malnutrition
What are the malabsorption problems seen commonly in patients with chronic pancreatitis? (4)
1) Dominant malabsorbed nutrient is lipid = steatorrhea
2 )B12 malabsorption (pancreatic enzymes cleage R-bond)
3) Can eventually get diabetes due to glucagon/insulin secretion
4) Vitamin K malabsorption → bleeding
Steatorrhea in chronic pancreatitis
Dominant malabsorbed nutrient is lipid = steatorrhea (oily, foul smelling, and/or buoyant stools), flatulence, weight loss
Due to decreased lipase and colipase in duodenum and decreased duodenal pH
Malabsorption occurs in later stages since only 10-20% of acinar cells required for maintaining lipase reserve
Complications of chronic pancreatitis (2)
1) Pseudocyst
2) **Ductal obstruction due to strictures or stones (NOT in acute pancreatitis)
Pseudocyst
fluid collection of liquefied/auto-digested pancreatic parenchyma containing a mixture of pancreas juice and clumps of semi-solid, necrotic tissue surrounded by granulation tissue
Resolve as pancreatitis improves, but if they persist, may grow/push on adjacent structures and require drainage
Treatment of chronic pancreatitis (5)
1) ETOH avoidance ** = Mainstay of treatment
2) Pancreas enzyme replacement for steatorrhea
3) ERCP and dilation, stent placement, or stone removal for duct obstruction
4) Celiac nerve block for pain
5) Surgical resection if refractory and severe
What is ERCP?
endoscopic retrograde cholangiopancreatography= visusalization and palliative stent placement across bile duct stricture to relieve cholestasis symptoms
When to use ERCP? (3)
Adenocarcinoma → Refer in patients to ERCP with stent if they have metastases, recurrent disease, or high surgical risk
Autoimmune pancreatitis → ERCP with placement of biliary stent effective in patients with jaundice or pruritus
Acute pancreatitis → consider ERCP for bile duct stone removal if it doesn’t pass on its own
Pathophysiology of autoimmune pancreatitis
IgG-4 + Plasma cells and lymphocytes infiltrate pancreas and its vessels → localized or diffuse enlargement of pancreatic parenchyma and narrowing of pancreatic duct and/or bile duct
Glandular atrophy, ductal dilation
**calcifications and steatorrhea are NOT features of AIP (features of chronic pancreatitis)
Symptoms of autoimmune pancreatitis?
- chronic epigastric or diffuse abdominal pain +/- cholestasis (jaundice, dark urine, itching)
- Typically males in ages 40-70
**Can masquerade as pancreatic cancer
Diagnosis of autoimmune pancreatitis (3)
Elevated serum IgG-4
Elevated total IgG, ANA, and RF
CT, US, or MRI → focally or diffusely enlarged pancreas with decreased enhancement and loss of lobular contour
Treatment of autoimmune pancreatitis (2)
6-week corticosteroid course (MUCH more treatable than cancer)
ERCP with placement of biliary stent effective in patients with jaundice or pruritus
Neuroendocrine tumors of the pancreas
Histology
Presentation (3)
aka carcinoids
Histology: arise from enterochromaffin cells of lung, GI tract, or pancreatic islets
Presentation:
1) Most are clinically silent and detected on routine imaging
2) Larger ones cause pain
3) Symptoms of hormone excess (insulin, glucagon, gastrin, VIP, somatostatin)
Diagnosis and treatment of neuroendocrine tumors of the pancreas
Diagnosis: imaging studies, FNA
Treatment: surgical resection or close observation in high surgical risk patients
Adenocarcinoma of the pancreas epidemiology
4th leading cause of cancer mortality in men and women in US
5-year survival only 5%
Adenocarcinoma of the pancreas histology
typically arise from ductal epithelial cells (acinar cells 5-10% of time)
Form primitive mucin-positive gland-like structures
Elicit strong fibrotic reaction (desmoplasia) → hard to penetrate with chemo
Adenocarcinoma of the pancreas risk factors
family history, tobacco use, chronic pancreatitis, obesity, genetic syndromes (VHL, Peutz-Jeghers)
Adenocarcinoma of the pancreas symptoms
usually present late, with locally advanced/metastatic disease
1) Weight loss, abdominal/back pain (late symptom)
2) **Symptoms of bile duct obstruction → jaundice, dark urine, pruritus
- Due to bile duct obstruction at head of pancreas
3) Hypercoagulable state (Trousseau’s syndrome)
Adenocarcinoma of the pancreas diagnosis and treatment
Diagnosis: contrast abdominal CT, fine needle aspiration (FNA), biopsy
-Endoscopic ultrasound is test of choice to stage pancreatic cancer
Treatment: surgical resection
4 names of proton pump inhibitors
Lansoprazole, Omeprazole, Esomeprazole, Lansoprazole
How do PPIs get into cells and act?
prodrug → systemic circulation → diffuses into parietal cells → activated in canaliculi to sulfenamide → then “trapped”
Mechanism of action of PPIs
Irreversibly inactivates H+-K+-ATPase
ONLY inactivates ACTIVE pumps
→ 2-5 days for steady state effect
Must take PPI before a meal so Cp max coincides with maximal pump secretion
Inactive pumps stored inside cell, put on membrane when active
Acid suppression for > 18 hours
Uses of PPIs (5)
1) GERD (#1 agent)
2) Peptic ulcer disease
- Used in triple therapy in order to increase gastric pH and promote healing with H. pylori associated PUD
3) NSAID induced ulcers (prevention and treatment)
4) Prevention of stress gastritis (IV infusion)
5) Zollinger-Ellison Syndrome
Side effects of PPIs
dosage reduction for who?
chronic use results in what?
Dosage reduction required for HEPATIC disease (not renal)
Remarkably safe drug, minimal side effects (headache, GI pain, nausea, diarrhea, constipation)
Acid rebound upon discontinuation (taper dose)
-Gastrin levels are increased due to decreased acidity, but proton pump is blocked so pH stays high → remove PPI → rebound acidity
Chronic use → increased fracture risk (decreased Ca2+ absorption), decreased Mg2+ absorption
Misoprostol
mechanism of action
indication
Prostaglandin analog → acts on epithelial cells to decrease H+ secretion and increase mucus bicarbonate
Indicated for NSAID induced ulcers - not first line (PPIs are)
Misoprostol
side effects (2)
diarrhea
uterine cramping, contraindicated in pregnancy
Sucralfate
mechanism of action
side effects
Sulfated disaccharide Al+++ salt → binds necrotic tissue forming protective barrier
Activated by acidic pH → give on empty stomach
Not absorbed → few side effects (constipation)
H2 antagonist drug names (3)
Cimetidine, Famotidine, Ranitidine
H2 antagonists mechanism of action
competitive reversible block of H2 receptors on basolateral membrane
H2 antagonists uses (3)
GERD
PUD (usually PPIs used instead)
Stress related gastritis (IV H2 antagonist)
PPI vs. H2 antagonist (3)
Less efficacious than PPIs
More rapid onset of action than PPIs → better for acute gastritis
Better at blocking nocturnal H2 than meal stimulated (ACh-gastrin) acid secretion, but PPIs are still more effective
Side effects of H2 antagonists (4)
Generally well tolerated
1) CNS dysfunction (mental status change) in elderly or renally impaired
2) Gynecomastia (chronic high dose cimetidine)
3) Tolerance possible with continued use
DDIs and dosage reduction in who?
DDIs: Cimetidine inhibition of CYP450 metabolism**
Renal excretion - dosage reduction with renal dysfunction
Antibiotic ulcer therapy
purpose?
used to eradicate H. pylori infection that damages epithelial cells and increases susceptibility to ulceration (associated with 85% of duodenal ulcers)
**Confirm eradication (stool antigen test)
Triple therapy (ulcer therapy)
Clarithromycin-Amoxicillin/Metronidazole-PPI
Quadruple therapy (ulcer therapy)
bismuth subsalicylate-Metronidazole-Tetracycline-PPI (or H2 Antagonist)
Sequential therapy (ulcer therapy)
amoxicillin-PPI x 5 days, THEN clarithromycin-Tinidazole / Metronidazole-PPI x 5 days
Ideal antacid has what properties? (5)
rapidly raise pH (to pH=4)
nonabsorbable
long acting,
no adverse effects
no drug-drug interactions
Calcium carbonate (Tums)
Rapid, prolonged neutralization → rebound secretion
Safe, but NOT for chronic use (except when used as Ca2+ supplement)
Side effects: Constipation, hypercalcemia, renal calculi
Aluminum hydroxide/Aluminum carbonate
Widely used
Binds phosphate in gut (used in CKD)
Side effect: constipation, CNS toxicity with chronic intake
Magnesium hydroxide (milk of magnesia)
side effects
osmotic diarrhea
Prokinetic agents (3)
Metoclopramide (Reglan)
Tegaserod, Cisapride
Metoclopramide (Reglan)
Mechanism of action
dopamine antagonist → block presynaptic inhibition of ACh release → increase in coordinated contractions → enhance transit
Weak 5-HT antagonist at chemoreceptor trigger zone → relieve n/v
Metoclopramide (Reglan)
side effects
somnolence, dystonic reactions, tardive dyskinesias (EPSEs)
Tegaserod, Cisapride
Mechanism of action
5HT4 receptor agonists → direct stimulation of ACh release → increase coordinated contractions and transit in esophagus and stomach
Tegaserod, Cisapride
use
reduces bloating of irritable bowel syndrome (IBS)
Tegaserod, Cisapride
side effects
Cisapride → LIFE THREATENING ARRHYTHMIAS (increase QT)
Tegaserod → linked to strokes, MI, angina
Epithelium in esophagus
non-cornified squamous epithelium
Muscle within the esophagus
Upper portion → skeletal muscle, midway → mix skeletal/smooth, lower ⅓ → solely smooth muscle
Mucus glands in esophagus
present in dermis → lubrication, assist in swallowing
Esophageal gastric junction
contains small incomplete sphincter with maintained muscular contraction to prevent reflux of stomach contents
Does the esophagus contain a mucous covering?
NO
Cardia
small area with mucus secreting glands around entry of esophagus
Fundus
main body of stomach, secretes acid, peptic digestive products, and mucus
Pylorus
secretes mucous, contains endocrine cells that secrete gastrin hormone
Surface mucous secreting cells
- face cavity of stomach, arranged in folds along underlying lamina propria
- Contain large vesicles with mucins and bicarbonate → local discharge onto surface to provide viscous protective layer
- Shelter epithelial cells against stomach acid and abrasion from churning chime - Have short microvilli on surface with glycoprotein/glycolax covering
Gastric pits
spaces between epithelial folds, continue deep into mucosa as one or more tubular gastric glands
Gastric glands
- contain differentiated epithelial cells crucial for function of stomach (digestion of food at acidic pH)
- Stomach lumen extends to very body of gastric glands
Stem cells of the stomach
Enable constant renewal of gastric epithelium (every 3-5 days)
- Deep in glands, turn over every 6-12 months
- Located in upper neck region, undifferentiated
→ downward to specialized cells on gastric glands
→ upward mucous-secreting cells
Chief cells
protein secretors with apical granules and elaborate basal RER
- Secrete pepsinogen → converted to pepsin in presence of acid
- Pepsin: protease, optimal function at low pH
- Derived directly from stem cells
Parietal cells (5)
unique acid producing cells
- H+/K+ ATPase pumps H+ ions into lumen of gastric glands against high concentration gradient
pH of gastric juice = 1-1.5 - Extensive microvilli bordering canaliculi → enormous surface area for pumping H+ into lumen
- Lots of mitochondria
- Stimulated to produce acid by gastrin and histamine
- Secrete intrinsic factor
Zollinger-Ellison Syndrome
excessive secretion of gastrin → overproduction of HCl by parietal cells → duodenal ulcers
Enteroendocrine cells
APUD cells (amine precursor uptake decarboxylation), typically oriented toward vascular side to release into bloodstream
4 types of enteroendocrine cells
- G-cells: secrete gastrin, located in pylorus
- A-cells: secrete glucagon
- EC-cells: secrete serotonin (serotonin also taken up and stored by platelets)
- D-Cells: secrete somatostatin, widely distributed in middle portion of stomach
Rugae
Stomach
- longitudinal folds in stomach wall
- Disappear upon distension
Plicae circularis
(small intestine)
- permanent transverse-oriented folds covered with villi
- Increase surface area of small intestine 8x
Duodenum
- low pH chyme from stomach enters duodenum upon relaxation of pyloric sphincter
- Digestion continues in duodenum at higher pH and with enzymes released from pancreas and present at surface of intestinal mucosa
- Absorption also occurs due to high surface area here
Brunner’s glands:
Duodenum:
Jejunum:
Ileum:
Duodenum: Present
Jejunum: Absent
Ileum: Absent
Goblet cells:
Duodenum:
Jejunum:
Ileum:
Duodenum: +
Jejunum: ++
Ileum: +++
Lymphatic tissue:
Duodenum:
Jejunum:
Ileum:
Duodenum: +
Jejunum: ++
Ileum: ++++
Plicae Circularis:
Duodenum:
Jejunum:
Ileum:
Duodenum: +
Jejunum: Best developed
Ileum: +
Number of Villi:
Duodenum:
Jejunum:
Ileum:
Duodenum: Most numerous
Jejunum: decreased distally
Ileum: least abundant
Parts of the intestine (5)
- Enterocytes
- Goblet mucous cells
- Enteroendocrine cells
- Intestinal glands
- Intestinal villi
Enterocytes of the small intestine
- epithelial cells, also contain microvilli on their surface,
- increase surface area 30x
- Glycolax and glycoproteins cover microvilli → digestive processes within glycolax due to digestive enzymes found in matrix
Goblet mucous cells of small intestine
scattered between absorptive/digestive cells
- Produce mucus for protection/lubrication
- Least abundant in duodenum
Enteroendocrine cells
also in SI, secrete different stuff than stomach ones
Intestinal glands (3)
- Crypts of lieberkuhn
- Paneth cells
- Brunner’s glands
Crypts of Lieberkuhn
simple tubular glands, penetrate from base of villi deeper into mucosa
- Continuous with surface epithelium
- Stem cells most abundant in lower third of crypts → give rise to other cells (mucous cells, enterocytes, Paneth cells)
Paneth cells
contain large eosinophilic granules with lysozyme, phospholipase, and antibacterial peptides called defensins
Brunner’s glands
only in duodenum, release contents into crypts
- Secrete large amounts of mucins and bicarb to neutralize acid arriving in pyloric sphincter
Intestinal villi
highly structured
- Loose lamina propria core containing small blood vessels, lymphocytes, and lymphatic spaces that joint at the lacteal
- Contains lacteals: larger lymphatic vessel in center of intestinal villa-> larger lymphatics and proceed to bloodstream via thoracic duct
Function of lacteal (2)
- Passage for fluid entering lumen of intestine
2. Transport for lipoprotein droplets (chylomicrons) exocytosed by enterocytes on side facing lamina propria
Enterocytes and fatty acids
take up fatty acids and monoglycerides form lumen of gut, and resynthesize them to di- and triglycerides → release them by exocytosis on opposite side
Nutrient taken up by capillaries via hepatic portal system of liver
Digestion in the small intestine
- Chyme neutralized → enzymes produced by pancreas and enterocytes digest proteins to AAs, complex carbs to single monomers (glucose, galactose), and lipids to fatty acids and monoglycerides
- Muscularis externa: inner circular and outer longitudinal layers in intestine → movement of luminal contents by peristalsis
- Segmented movement with alternate contraction and relaxation of segments → back and forth movements that agitates luminal contents
Main pancreatic duct
Main pancreatic duct joins common bile duct near its entry to duodenum
- Sphincter of Oddi (hepatopancreatic sphincter)
Organization of pancreatic cells
Organized into cluster of pancreatic acinar cells arranged at end of common duct
Basal side of acinar cells
full of RER, synthesis of proteins for secretion
Apical side of acinar cells
secretory granules (zymogen granules) with packaged product that gets secreted into ducts
- Most secreted enzymes initially inactive (zymogens)
- Prevents autodigestion of proteins/lipids of pancreas en route via ducts to duodenum
Inactivated enzymes secreted by pancreas (5)
trypsin, chymotrypsin, elastase, carboxypeptidase, triacylglycerol lipase
Trypsinogen activated by ____
enterokinase
Not secreted by pancreas, membrane anchored enzyme in apical plasma membrane of duodenal digestive/absorptive cells (epithelial enterocytes)
Trypsin
Activates other zymogens by proteolysis
Amylase
degrades starch to glucose and maltose
Synthesized in active form in pancreas
Ribonuclease
cleaves RNA
Synthesized in active form in pancreas
Centroacinar cells
cells in acini, represent beginning of duct system
Secrete much of the volume of pancreatic juice (water, bicarb)
- Help Brunner’s glands neutralize acid
- Secretion under control of secretin and cholecystokinin
Enterocytes of intestine
have complex glycolax at their surface
Some of final digestive processes occur in this layer just outside cell
Digestion of starches
amylase (from pancreas) digestion → maltose and isomaltose → broken down by maltase and isomaltase (membrane-anchored enzymes in apical plasma membrane of enterocytes) → glucose
Glucose absorbed via nearby glucose transporters = most effective absorption instead of being consumed by bacteria
Digestion of lactose
Lactase → on enterocyte surface, cleaves lactose → glucose + galactose
Absence of lactase → lactose intolerance because bacteria utilizes undigested lactose
Three types of fluids secreted by salivary glands
- serous
- Mucous
- Mixed
3 types of salivary glands
- submandibular
- sublingual
- parotid
Type of fluid secreted by submandibular glands
mixed
Type of fluid secreted by sublingual glands
mucous (lubricative and protective)
Type of fluid secreted by parotid glands
serous (watery, contain enxymes- amylase, RNAse, DNAse)
Serous epithelial cells also transport IgA class Ig that together with lysozyme and peroxidase provide antibacterial action
Organization of salivary glands
Organized in acinar design:
Contraction of myoepithelial cells propel salivary secretions form acini
Large intestine
cecum, appendix, transverse colon, descending colon, and rectum
- Smooth, lacks plicae and villi
- Contains numerous straight tubular glands/crypts
- Epithelial layer: abundant mucous-producing cells and absorptive cells
Function of large intestine
recovery of water and salt during concentration of fecal material
Columns of morgagni
longitudinal structural folds of mucosa located near distal portion of rectum
Lamina propria and submucosa of LI contain numerous _______
Lymphocytes
___ of the wall of the colon is muscular
2/3
Muscle in the colon
- Large band of circular smooth muscle
- Muscular specializations in longitudinal layer:
- Taeniae: bands in this layer - segmented contraction → sacculation of bowel which compresses and segments fecal material
- Anus: where circular layer is thickened to form internal anal sphincter
- External anal sphincter is circular striated muscle
Main distinguishing features of stomach: 3
- Thick mucosa, glands that branch deep into mucosa with acini at end of branches
- Acinar/Chief cells at end running down to muscularis mucosa
- pH = 1-2 → kill bacteria, and denature proteins
Main distinguishing features of small intestine (2)
- Villi on surface specialized for absorption, lined by epithelium
- Small crypts at end of folded epithelium
Main distinguishing features of colon (1)
thick mucosa with linear, highly regular crypts filled with mucous secreting cells
General features of normal GI motility
Requires complicated coordination between CNS (SNS and PNS) and enteric nervous system with the gastric musculature
Gastric pacemaker cells: drive baseline motility of stomach (not well understood) - Interstitial cell of cajal
GI motility in the proximal stomach (cardia, fundus, body)
area relaxes upon ingestion of food = Receptive relaxation
Main role of proximal stomach is storage with minimal pressure increase
GI motility in distal stomach (antrum)
controls mechanical (grinding) and enzymatic digestion and processing → liquid chyme sent in small amounts to SI
Contraction of distal stomach → gastric emptying into duodenum
Physiology of gastric emptying (4)
- Receptive relaxation (vagally mediated inhibition of body tone)
- Swallowing induced vagal response
- Gastric Accommodation: smooth muscle relaxation elicited by mechanical distention of stomach (gastric mechanoreceptors)
- -Vasovagal response - Liquid emptying by tonic pressure gradient
- Solid emptying by vagally-mediated contractions
- Residual solids emptied during non-fed state by MMC (migrating motor complex) every 90-120 minutes
What can cause motility disorders? (4)
- chemical substances (inside and outside body) = NEUROPATHIC
- Diseased GI muscles: genetic defect (muscular dystrophy) or acquired (progressive systemic sclerosis) = MYOPATHIC
- Abnormalities of interstitial cells of Cajal - pacemaker cells
- CNS disorders (input for SNS and PNS)
Function of colon
transport, store, and expel stool after absorbing majority of luminal fluid
Two types of colonic motor activity
- Low amplitude tonic and phasic contractions for mixing luminal contents (Haustra)
- High amplitude propagated contractions (HAPCs) for propelling
What increases colonic motility?
Colonic motility increases after meal (gastrocolonic response) and on awakening
Causes of constipation (7)
- Drugs, mechanical
- Metabolic: DM, hypoK, hyperCa, hypoMg, hypothyroid
- Myopathy: amyloid, scleroderma
- Neurogenic: Parkinson’s spinal cord injury, MS, autonomic neuropathy, Hirschsprung’s
- Other: pregnancy, immobility
- IBS-C
- Normal transit, slow transit, dyssynergic defecation
Achalasia
esophageal motility disorder due to inflammatory destruction of neurons in myenteric plexus of esophagus
- Predominant destruction of inhibitory neurons that affect relaxation of esophageal smooth muscle → failure of appropriate LES relaxation after swallowing → esophagogastric junction outflow obstruction
- Spares cholinergic neurons that contribute to LES tone
- Absence of peristalsis
Symptoms of achalasia
dysphagia to solids and liquids, regurgitation of undigested food
Diagnosis of achalasia
esophageal manometry → incomplete relaxation of LES, aperistalsis in smooth muscle esophagus
Scleroderma
multi-system disorder, skin and GI involvement mostly
Small vessel vasculitis → vascular derangement and resultant smooth muscle atrophy and fibrosis of multiple organs
Esophageal involvement in scleroderma (3)
Myopathic process
- Atrophy of smooth muscle → weak peristalsis → dysphagia
- Atrophy of smooth muscle → weak LES → GERD
- Unrepentant GERD → esophagitis → stricture
Stomach involvement in scleroderma
delayed gastric emptying
Diagnosis of esophageal involvement in scleroderma
esophageal manometry → weak/absent esophageal body peristalsis
Differentiate from achalasia due to weakened LES pressure
Spastic disorders of esophagus
conditions of uncertain etiology, peristalsis preserved
Symptoms of spastic disorders of esophagus
chest pain and dysphagia
Pathophysiology of spastic disorders of esophagus
related to overactivity of excitatory nerves, and impairment of inhibitory innervation or overreactivity of smooth muscle response
EX) Jackhammer esophagus = lots of red on esophageal manometry, with high pressure and long contraction time
Gastroparesis
“Stomach paralysis”, delayed gastric emptying in absence of mechanical obstruction
Impaired transit of food from stomach to duodenum
Symptoms of gastroparesis
nausea, vomiting, bloating, early satiety, postprandial abdominal distension and pai
Causes of gastroparesis (4)
- Idiopathic, post-infection
- Post-surgical (vagal nerve injury) or myenteric plexus injury
COMMON with thoracic surgical procedures (lung transplant) - Diabetic (autonomic neuropathy), medication related (opiates)
- Others: paraneoplastic, rheumatologic, neurologic, myopathic (scleroderma)
Diagnosis of gastroparesis
scintigraphic gastric emptying (gastric emptying study)
Management of gastroparesis (4)
- Lifestyle and dietary measures: small and infrequent meals, low-fat and low-residue diet, glucose control in diabetics
- Medications: prokinetic agents, antiemetics
- Gastric electric stimulation
- Surgery (removal of stomach) - last resort
Chronic intestinal pseudo-obstruction (CIPO)
Signs and symptoms of mechanical obstruction of small bowel without a lesion obstructing flow of intestinal contents
- Characterized by presence of dilation of bowel on imaging
- Major manifestation of small intestinal dysmotility
Complication of CIPO
small intestinal bacterial overgrowth: stasis → bacterial overgrowth → fermentation and malabsorption
Causes of CIPO (4)
- Underlying neuropathic disorder involving enteric nervous system or extrinsic nervous system (Parkinson’s Shy-Drager syndrome, Diabetes)
- Infectious (Chagas)
- Myopathic disorder (involving smooth muscle)
EX) Scleroderma, amyloidosis, eosinophilic gastroenteririts - Or abnormality in interstitial cells of Cajal
CIPO in children
mostly congenital, mostly primar conditions, absent MMC predicts need for IV nutrition, ⅓ of infants born die in 1st year of life
Hirschsprung’s disease (2)
Congenital absence of myenteric neurons of distal colon (neuropathic motility disorder)
No reflex inhibition of the IAS following rectal distention (No Recto-anal inhibitory reflex)
Dyssynergic defection
Disorder in coordination of pelvic floor musculature - paradoxical contraction of pelvic floor and external anal sphincter with attempts at defecation
Diagnosis of dyssynergic defaction
anorectal manometry
Treatment of dyssynergic defaction
Biofeedback therapy is effective
Esophageal manometry
assessment of esophageal body peristalsis and upper and lower esophageal sphincter function
- Transnasal, intraluminal manometry catheter containing pressure sensors → from nares into stomach, assess esophageal motility as patient swallows repeated small boluses of water
- UES relaxation (red color) → esophageal peristalsis from top to bottom (proximal peristalsis of striated muscle and distal peristalsis of smooth muscle) → post-deglutitive LES relaxation
Gastric emptying studies
Aka gastric scintigraphy
Low fat EggBeaters radiolabeled with 1 mCi Technetium 99, measure percentage remaining after certain amount of time
Abnormal gastric emptying study
retention >60% at 2hr or >10% at 4hrs
Wireless motility capsule (WMC)
used to assess for gastroparesis and motility disorders of small intestine and colon
- Measures pressure, temperature, and pH as it traverses GI tract
Antroduodenal manometry
- Measure motility of SI with pressure sensors
- Measure pressure waves that result from phasic contractions of circular muscle layer
- Neuropathic process: discoordinated infrequent contractions
- Myopathic process: nothing happening even though nerves stimulating SI tract intact
Sitz marker study
Colonic transit study
Swallow 24 capsules containing radiopaque markers on Day 1 → plain abdominal xray on Day 5
- Less than 5 markers = normal
- > 5 markers in recto-sigmoid suggests defecatory disorder
- > 5 markers scattered throughout colon = slow transit
Anorectal manometry
- Primary means of assessing defecation disorders
- Catheter with pressure sensors placed in anus and rectum
- Resting pressure, stimulated defecation, rectal sensation testing, and recto-anal inhibitory reflex testing are all tested
Esophageal peristalsis is altered in (2)
achalasia, scleroderma
LES relaxation is altered in
achalasia
LES tonic contraction is altered in
scleroderma
Gastric emptying is altered in (2)
gastroparesis, functional dyspepsia
Small bowel peristalsis is altered in
CIPO
Colonic transit is altered in
slow transit constipation (scleroderma)
Sphincter dysfunction is altered in (2)
Hirschsprung’s, dyssynergic defecation
