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Flashcards in Miscelania Deck (207):

Where are AAs and monosaccharides absorbed?

Duodenum and Jejunum


Where are Cobalamine (B12) and bile salts/acids absorbed?



cells of Cajal

regulate electrical signals, can influence amplitude, but not frequency. Use Ca and K


enterochromaffin cells

use 5HT to signal myenteric plexus about the gut situation


parasympathetic and sympathetic

- Parasympathetic: mostly cholinergic of vagus nerve; stimulates activity of the enteric plexuses, increases GI motility and secretory activity.

- Sympathetic: mostly adrenergic, generally inhibits activity of the enteric plexuses, decreases GI motility, contracts GI sphincters, constricts GI microvasculature



primary excitatory transmitter from sensory cells and from motoneurons to muscle, epithelium, secretory cells and at interneuronal junctions. increases intracellular Ca++


Gastrin releasing peptide

released from vagal nerve endings to stimulate G cell secretion of gastrin.


Substance P

(tachykinin) - an excitatory transmitter generally co-released with acetylcholine.


Vasoactive Intestinal Peptide

(VIP) – Promotes motility
Relaxes smooth muscle in esophagus and stomach
Stimulates fluid secretion and promotes dilation of the GI vasculature. increases cAMP


Nitric Oxide

an inhibitory transmitter co-release with VIP from inhibitory motoneurons, hydrophobic- intracellular targets.



Gastrin – G cells in antrum of stomach detect amino acids leading to pepsinogen and H+ release by parietal cells.


Cholecystokinin (CCK)

I cells in D/J detect fat and amino acids, secretion of pancreatic enzymes and bile salts involved in fat uptake



S cells primarily in D/J detect acid stimulates secretion of pancreatic juice including bicarbonate and inhibits gastric motility.


Gastric Inhibitory Peptide or Glucose-Dependent Insulinotropic Peptide (GIP)

K cells in D/J detect carbohydrates and fat to inhibit gastric acid secretion and stimulate insulin release from pancreas.



secreted by endocrine cells; released cyclically during fasting state to initiate Migrating Motor Complex


respiratory quotient

Fat has the lowest RQ, Carbs the highest


Protein metabolism

1g protein= 6L O2 and 4.8L CO2


Nerve influences on saliva

Parasympathetic (glossopharyngeal and facial): acts through VIP and acetylcholine on muscarinic receptors to increase secretion of watery saliva.

Sympathetic (cervical sympathetic chain) acts through norepinephrine on β1- and α1 adrenergic receptors to secretion of viscous saliva



subjective sensation of dryness of the oral mucosa


alpha and beta pancreatic cells

beta release insulin, alpha release glucagon (in response to high protein levels)


Intestinal epithelial cells

Convert glutamine, glutamate and aspartate from the diet to a-ketoglutarate.



Use short chain fatty acids produced by gut bacteria.


glucagon receptor binding

Ligand binding causes activation of adenylate cyclase, production of cAMP, and activation of PKA

PKA activation in hepatocyte:
Glycogen synthase is phosphorylated and inactive.
Glycogen phosphorylase kinase is phosphorylated and active.
Glycogen phosphorylase is phosphorylated and active.


gluconeogenesis chemistry

The ATP to power gluconeogenesis comes from the FAD(2H) and NADH reduced by fatty acid beta oxidation.

The acetyl CoA produced by fatty acid beta oxidation is a substrate for ketone body synthesis.


muscle and fasting

Skeletal muscle
Proteolysis produces free amino acids. Branched chain amino acids are used by the muscle as fuel. Alanine and glutamine are exported for use as gluconeogenic substrates by the liver.
As the fast prolongs, skeletal muscle can use ketone bodies for energy.

Cardiac muscle
Fatty acid beta oxidation increases; glycolysis decreases.


Hypercatabolism chemistry

Lots of catecholamines for the first day, then they decrease sharply, glucagon spikes immediately, slowly peters off, cortisol slowly increases over a day or so



Amylase activity is highest in the duodenum.
Amylase is an endoglycosidase. It cuts a-1,4 bonds in polysaccharides.



Midgut herniates at 4th week and returns approx. 10th week.
Rotates around the axis of SMA 270 degrees in counterclockwise direction
Final Position (ligament of Treitz LUQ/cecum RLQ)

Complete nonrotation is the most frequent
Forming no C-Loop, the ligament of treitz on the right side of the abdomen and does not cross midline.

First month of life
Bilious emesis
Toxic (if late)

Plain abdominal x-ray
Upper GI contrast study
Duodenum the right side of abdomen with birds beak

IV fluid resuscitation
Placement of nasogastric tube
Foley catheter placement
Ladd’s procedure

Ladd’s procedure
Evisceration and detorsion
Division of ladd’s bands (ascending colon to duodenum)
Broadening of the mesentery


Pyloric Stenosis

1st born males
Improper innervation of pyloric smooth muscle
Projectile, non-bilious vomiting
May have recent history of “formula intolerances”

Baby acts hungry

Eventually will become dehydrated
No tears when baby cries
Infrequent wet diapers

Nature of emesis:
What color is it?– the most important question to ask
Non-bilious, curdled milk/formula, could have rust tint if presentation has been delayed

Bilious… not pyloric stenosis, could be midgut volvulus
Can be catastrophic (fatal) if not recognized



Clinical Triad of Symptoms:
Colicky abdominal pain
Bilious emesis
“Currant jelly” stools

Management– Barium Enema


Meckel’s Diverticulum

Small bowel diverticulum--- TRUE diverticulum

2% of population
Within 2 feet of ileocecal valve
2 types of heterotopic tissue: gastric (50%) and pancreatic
2 inches in length
2 year old


Hirschsprung’s Disease

Absence of Ganglion cells in the myenteric and submucosal plexus
Aganglionosis always involves distal rectum
Abdominal distention
Bilious emesis
Failure to pass meconium in the first 24 HRs



abdominal contents sticking out WITH a sac



abdominal contents sticking out WITHOUT a sac


Acinar cells

secrete digestive enzymes

Gastric phase: activated by parasympathetic efferents (ACh) from vagal centers in the brain and secondary to gastrin release

Intestinal phase: activated by vago-vagal reflex and
by fat/amino acids in duodenum- I cells release CCK

Ca most important for signaling


Centroacinar cells

dilute pancreatic enzymes and make rich in sodium and bicarbonate


duct cells

dilute pancreatic enzymes and make rich in sodium and bicarbonate

H+ ions cause S cells to release secretin activating ductal cell secretion of bicarbonate


Regulation of CCK

During cephalic and gastric phases, vagal stimulation causes release of pancreatic enzymes including Monitor Peptide.
During intestinal phase, amino and fatty acids cause release of CCK-RP.
CCK-RP and Monitor Peptide causes release of CCK from I cells into the blood.
CCK increases release of Monitor peptide and pancreatic enzymes.
Pancreatic enzymes digest luminal nutrients, CCK-RP, and Monitor peptide turning off CCK secretion


Activation of Pancreatic Enzymes

Enteropeptidase from duodenal brush border membranes cleaves trypsinogen to its active forms trypsin.
Trypsin then activates lipases and endopeptidases chymotrypsin and elastase.



Cystic fibrosis
Occlusion of pancreatic duct: gallstones, malignancy
Alcohol can be metabolized into products that cause hyperstimulation of acinar cells resulting in intracellular trypsin activation and cell death.

Upper abdominal pain from autodigestion of pancreatic tissue can lead to vomiting and sympathetic activation
Enzymes spill over into circulation- elevated serum amylase and lipase levels.
Malabsorption of fat and fat-soluble vitamins (A,D,E,K) steatorrhea
Malignancy, Diabetes, and Infections



an incretin -> increased insulin and decreased  glucagon
Oral glucose leads to higher insulin than IV glucose since glucose causes a release of glucagon-like peptide-1 (GLP-1) from intestinal L cells and glucose-dependent insulinotropic peptide (GIP) from K cells


satiety signalling cytokines

GLP1, CCK, Insulin, and Leptin



a peptide hormone produced in fundus of stomach during fasting stimulates appetite (orexigenic) and decreases energy expenditure through neuropeptide Y and agouti-related peptide


Kupffer cells

type of macrophage


Stellate cells

produce collagen
and store lipids like vitamin A


gallbladder contraction

During intestinal phase, CCK and vagal efferents activate gallbladder contraction and relaxation of the sphincter of Oddi



- impaired bile secretion

Primary Biliary Cirrhosis (destruction of cholangiocytes)
Primary Sclerosing Cholangitis (inflammation of bile ducts)
Pregnancy- progesterone reduces gallbladder smooth muscle tone

Bile accumulates in liver leading to metabolic dysfunction
Itching associated with bile regurgitate into the plasma
bile salts can be excreted into the urine
Hypercholesterolemia- cholesterol aggregation “lipoprotein X”
Deficiency of fat soluble vitamins



Range from grain of sand to golf ball size (20% of population);

Symptoms: upper right quadrant abdomen pain, fever, many people lack symptoms

1. Cholesterol stones- due to increased cholesterol or decreased bile acids treat with bile acid- ursodeoxycholic acid,
Less common pigment stones (calcium salts of unconjugated bilirubin)
Hemolytic anemia, infection of biliary tract leads to deconjugation

Outcome of blockage depends on where blockage is occurring jaundice, steatorrhea, and bleeding disorders


Hartnup disease

Inherited mutations in the SLC6A9 transporter (Bo) result in Hartnup disease. This condition results in the symptoms of pellagra because tryptophan is not absorbed or resorbed and can not be used to synthesize niacin.



Activation of AMPK inhibits protein synthesis and promotes autophagy.



The mTORC1 complex activates protein synthesis and inhibits autophagy.


ApoB-48 o

ApoB-48 is the major apoprotein of chylomicrons. It is encoded by the same gene as ApoB-100, the apoprotein of VLDL.

RNA editing produces ApoB-48 in intestinal epithelial cells. The unedited transcript produces full length ApoB-100 in hepatocytes

After chylomicrons enter the blood, they receive ApoCII and ApoE from high density lipoprotein (HDL).

Fatty acids and cholesterol taken up by the liver from chylomicron remnants can be repackaged with ApoB100 as very low density lipoprotein (VLDL).

VLDL serves a similar function as chylomicrons: To deliver fatty acid fuels to the tissues of the body.


Lipoprotein lipase (LPL)

Lipoprotein lipase (LPL) is an extracellular lipase in the capillary beds of muscle and adipose tissue. It is activated by ApoCII



RNA editing produces ApoB-48 in intestinal epithelial cells. The unedited transcript produces full length ApoB-100 in hepatocytes

After chylomicrons enter the blood, they receive ApoCII and ApoE from high density lipoprotein (HDL).

Fatty acids and cholesterol taken up by the liver from chylomicron remnants can be repackaged with ApoB100 as very low density lipoprotein (VLDL).

VLDL serves a similar function as chylomicrons: To deliver fatty acid fuels to the tissues of the body.


Aphthous ulcers

(canker sores): very common, shallow, superficial mucosal ulcerations, usually painful and often recurrent. Etiology is uncertain, with a variety of causes suggested (including minor trauma, local food sensitivity, and stress), but some may be associated with celiac disease or inflammatory bowel disease. Typically spontaneously regress within several weeks.


Fibroma (irritation fibroma)

reactive proliferation of squamous mucosa and underlying subepithelial fibrous tissue, typically secondary to chronic irritation.


Pyogenic granuloma

polypoid red lesion, composed of lobular reactive proliferation of capillaries (eruptive hemangioma). Usually occurs on the gingiva in children, young adults, pregnant women.



defined as inflammation of the tongue, but also used to describe the beefy-red appearance of the tongue encountered in certain deficiency states, such as vitamin B12 deficiency. Red appearance is secondary to atrophy of the papillae of the tongue and thinning of the mucosa. Combination of iron-deficiency anemia, glossitis, and esophageal dysphagia associated with esophageal webs is known as the Plummer-Vinson syndrome.


Geographic tongue

(benign migratory glossitis): migratory “map like” appearance of the tongue, due to focal loss of the papillae with formation of smooth red patches. Microscopically, intraepithelial neutrophilic inflammation is present. Patients are usually asymptomatic, but some may experience a mild burning sensation. Etiology is unknown; however, this condition does tend to run in families so there may be a genetic component.


Bisphosphonate-related osteonecrosis of the jaw

Bisphosphonate medications (such as Fosamax) are used to treat osteoporosis. One side effect with the use of this class of medication is focal mandibular and maxillary osteonecrosis. In some cases, the osteonecrosis occurs following minor trauma (such as a dental procedure).


Odontogenic cysts and tumors

odontogenic derived epithelial lined cysts of the jaws are common. Most common cysts include dentigerous cyst (originates around the crown of an unerupted tooth), odontogenic keratocyst (typically locally aggressive with high rate of recurrence), and periapical cyst (inflammatory). Many types of odontogenic tumors exist, with the most common and significant tumors being ameloblastoma and odontoma


Hairy leukoplakia

White, confluent patches of “fluffy” hyperkeratosis on the lateral sides of the tongue. Unlike thrush (candida infection), the lesion cannot be scraped off.

Occurs in immunocompromised individuals (HIV infection, treated cancer patients, organ transplant patients) secondary to EBV infection.

May be the first presenting sign of HIV infection.


Squamous papilloma

Exophytic papillary proliferation of squamous mucosa with fibrovascular core.

Some are associated with HPV infection; others may represent reaction to trauma/irritation.

Some squamous papillomas can undergo malignant transformation to in-situ and invasive squamous cell carcinoma.


Actinic cheilitis

Leukoplakic lesion of the lower lip with loss of the distinct demarcation between the lower lip vermilion border and the skin of the lip (above right, arrows); histologic findings include disordered maturation of the epithelium with cytologic atypia, increased mitotic activity, hyperkeratosis, and connective tissue solar changes


Nasopharyngeal angiofibroma

benign neoplasm composed of admixture of vascular and fibrous tissue. Occurring almost exclusively in young adolescent males and men before the age of 25. Most common clinical complaints are persistent nasal obstruction and epistaxis.


Sinonasal (Schneiderian) papillomas

typically occuring in adults, these are benign neoplasms arising from the sinonasal (Schneiderian) mucosa and are composed of a squamous or columnar epithelial proliferation. These papillomas occur in three forms: exophytic (septal), inverted, and oncocytic (columnar). The first two types can sometimes be associated with HPV. All of these papillomas can recur if incompletely excised, but the inverted type, which arises from the lateral nasal wall, is especially prone to recurrence to due its inverted growth pattern. Malignant transformation can also occur in the inverted and oncocytic papillomas


Nasopharyngeal carcinoma

rare tumor in the USA, but common in Africa (one of the most frequent childhood cancers in that location) and common in southern China (typically adults, rare in children at that location). There are three patterns of nasopharyngeal carcinoma: keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, and undifferentiated carcinoma. The last two patterns exhibit a strong association with EBV, and components of the EBV genome can be detected in the tumor cells. These tumors are frequently occult, and the first presentation can be metastasis in the cervical lymph nodes.


Laryngeal squamous papillomas

benign papillary squamous neoplasms, often times caused by HPV.



defined as dry mouth due to decrease in the production of saliva. Causes include Sjogren’s syndrome, previous radiation therapy, and side effect of prescribed medications.



defined as inflammation of the salivary glands. Many causes, including trauma, bacterial or viral infections (e.g. mumps), and autoimmune disease (e.g. Sjogren’s syndrome). Sialolithiasis (stone in the salivary duct) can lead to obstruction and secondary bacterial infection (often Staphylococcus aureus or Streptococcus viridans).



results from either blockage (retention mucocele) or traumatic injury (extravasation mucocele) to a minor salivary gland, with leakage of contents into the surrounding connective tissue stroma. Presents as a fluid filled mucosal nodule with varying degrees of inflammation. A ranula is a mucocele that arises when the sublingual duct is damaged. Ranulas can become quite large and dissect into the neck (plunging ranula).


Lymphoepithelial sialadenitis

Autoimmune disease involving the salivary glands.

Many of the cases (50%) represent salivary gland manifestations of Sjogren’s syndrome, a systemic autoimmune disease which can have involvement of the major and minor salivary glands and the lacrimal glands (dry mouth and dry eyes (keratoconjunctivitis sicca).

Pathologic features are polyclonal lymphoid inflammation of the salivary gland, leading to gland enlargement and characteristic lymphoepithelial lesion.

Other entities can cause morphology similar to LESA, such as HIV-associated sialadenitis (benign lymphoepithelial cysts).

Pathologic findings of LESA need to be distinguished from primary lymphoma of the salivary gland, many of which have the morphology of B-cell MALT lymphoma (although other types of lymphoma can occur).


Pleomorphic Adenoma

Most common salivary gland tumor; usually found in the parotid gland.

Benign tumor consisting of a mix of proliferating epithelial (ductal and myoepithelial) cells, associated with a mesenchymal matrix of myxoid, hayline, and chondroid (cartilaginous-like) tissue. It may be that all neoplastic tissue elements in this tumor may be of ductal or myoepithelial origin, hence the term pleomorphic adenoma.

Tumors typically present as painless, discrete masses. While seemingly well circumscribed, they have small extensions or protrusions such that simple enucleation of the tumor will lead to a recurrence rate of 25%.

Rarely, a carcinoma will arise in a pleomorphic adenoma. This typically occurs in tumors of long duration, and the carcinoma is often times poorly differentiated and high grade. Such tumors are called “carcinoma ex pleomorphic adenoma” or “malignant mixed tumor.”


Warthin Tumor

Second most common salivary gland tumor, found almost always in the parotid gland.

Multifocal in 10% and 10% are bilateral. Smokers have 8 times the risk of developing this tumor than nonsmokers.

This benign tumor is well encapsulated with a distinct microscopic appearance, demonstrating a papillary, cystic lesion with a dual layer of bland, neoplastic, eosinophilic (oncocytic) epithelium, associated with reactive lymphoid stroma.


Mucoepidermoid carcinoma

Most common malignant salivary gland tumor and the most common malignant salivary gland tumor in children.

Approximately 60-70% occur in the parotid gland.

Composed of a variable mixture of squamous cells, mucus-secreting cells, and intermediate cells.

While tumors grossly appear encapsulated, they often infiltrate at the margins microscopically.

Clinical course is dependant on the grade of the tumor: low grade tumors recur in about 15% of cases, and have a 5-year survival rate of more than 90% due to low frequency of metastases; high grade tumors recur in 25-30% of cases with a 5-year survival rate of only 50%.


Vitamin A

In the body, the alcohol of trans-retinol can be converted to:
carboxylic acid
ester with fatty acid (e.g. palmitate)

Found in: Red, yellow, orange fruits and vegetables.

Retinoic acid is soluble enough to be transported in the blood associated with albumin. Retinyl-fatty acid esters are transported in chylomicrons.

Stellate cells in the liver serve as the reservoir for Vitamin A storage.

Hepatocytes mediate retinol homeostasis in the body.
Retinyl esters go in. Sources:
Dietary: Chylomicrons
Stored: Stellate cells

Retinyl esters go out to. . .
Stellate cells (storage)
VLDL (to tissues)

Retinol goes out to serum in complex with transthyretin and retinol binding protein (RBP).

Retinoic acid goes out to serum complexed to albumin.

Retinol is important for vision, and vitamin A deficiency can manifest as night blindness. Vitamin A toxicity can result in blurred vision.

cis-retinal bound to the protein opsin is the photoreceptor rhodopsin. Light causes conversion to trans-retinal. Rhodopsin bound to trans-retinal activates a heterotrimeric G protein, closure of a Na+ channel, hyperpolarization of the rod cell, and signaling to the neuron.

Retinoic acid acts as a ligand for the retinoic acid receptors (RAR), retinoic X receptors (RXR) and some peroxisome proliferator activated receptor (PPARb and PPARd).

RAR, RXR, and PPAR act as ligand activated transcription factors.

Vitamin A deficiency:
retarded growth
increased susceptibility to infections
keratinization of epithelial cells
night blindness
xeropthalmia (dry eye due to keratinization)
Bitot’s spots

Doses in vast excess of this can cause. . .
blurred vision
desquamation of skin
liver damage (from excess stellate cell growth and proliferation)
conjunctivitis, eye pain


Adenoid cystic carcinoma

Slow growing, often relentless salivary gland carcinoma with predilection for neural invasion.

While this tumor can occur in the major salivary glands, approximately 50% occur in the minor salivary glands (most common malignant tumor of the minor salivary glands).

Despite surgical resection, 50% disseminate to lungs, bone, liver, and brain, often decades after removal. While 5-year survival rate is 60-70%, survival drops to 30% at 10 years and 15% at 15 years.


Acinic cell carcinoma

Malignant salivary gland tumor composed of neoplastic epithelial cells resembling salivary gland acinic cells.

Survival at 5 years is approximately 90%, but drops to 60% at 20 years.


Salivary gland adenocarcinomas

Salivary duct carcinoma: microscopically resembles ductal breast carcinoma, typically seen in the elderly in the major salivary glands.

Polymorphous low-grade adenocarcinoma: usually seen in the minor salivary glands, often in the palate.


Esophageal mucosal webs

protusions of mucosa that can cause obstruction; usually seen in the upper esophagus; upper esophageal webs associated with chronic iron-deficiency anemia, glossitis, oral leukoplakia, and spoon nails is known as the Plummer-Vinson syndrome.


Esophageal rings (Schatzki rings)

like webs but thicker and circumferential; may contain muscularis propria; located in the lower esophagus.


Zenker’s diverticulum

Located above the upper esophageal sphincter as an outpouching of mucosa and submucosa through a weakend posterior cricopharyngeus muscle; not a true diverticulum.

This diverticulum can become large enough to accumulate food, producing a mass and symptoms of painful swallowing, halitosis, regurgitation, and diverticulitis.


Mallory-Weiss syndrome

defined by the presence of longitudinal mucosal lacerations in the distal esophagus and proximal stomach, usually associated with severe retching or vomiting. A history of heavy alcohol use leading to vomiting is seen in 40-80% of patients. Mallory-Weiss syndrome can be one cause of upper GI bleeding.


Boerhaave syndrome

refers to transmural rupture of the distal esophagus with pneumomediastinum (air in mediastinum) and can be a complication of the Mallory-Weiss syndrome.


Hiatal hernia

results from separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the defect; this can be a congenital condition, but most are acquired later in life (50% of adults over the age of 50 have hiatal hernia); in about 10% of patients, get symptoms similar to GERD with inflammation, ulceration, stricture, and hematemesis (vomiting blood). 95% of hiatal hernias are of the sliding type (Type 1).


Eosinophilic esophagitis

Esophageal biopsies show greatly increased eosinophilic inflammation (>15 eosinophils/HPF) with basal epithelial hyperplasia, in the absence of acute inflammation. Characteristic visual endoscopic findings may be present.

Adults and teenagers may present with food impaction, persistent dysphagia (difficulty swallowing), or GERD symptoms that fail to respond to medical therapy; children can present with feeding disorders, vomiting, abdominal pain, dysphagia, and food impaction.

Disorder is thought to represent some type of allergic reaction to food allergens but underlying pathogenesis is not completely understood; many patients have other allergies, such as allergic rhinitis, atopic dermatitis, or asthma. Mild eosinophilia may be seen in 40-50% of patients.


Esophageal adenocarcinoma

Adenocarcinoma most often (95%) arises in the background of Barrett’s esophagus and long-standing GERD. Those with glandular dysplasia are at increased risk.

Progression of Barrett’s esophagus to adenocarcinoma occurs through stepwise acquisition of genetic and epigenetic changes. Amplification of EGFR can be seen in some tumors.

Adenocarcinomas are usually located in the distal third of the esophagus. Patients can present with pain on swallowing, hematemesis, chest pain, and progressive weight loss.

Some advanced tumors are treated with neoadjuvant radiation and chemotherapy prior to resection. Endoscopic mucosal resection (EMR) can be used to treat tumors with no or minimal invasion.

Staging is based on tumor invasiveness, presence of lymph node metastases, and distant metastases (T, N, M).


Esophageal squamous cell carcinoma

Risk factors include alcohol and tobacco use, caustic esophageal injury, achalasia, tylosis (genetic disorder characterized by thickening (hyperkeratosis) of the palms and soles), Plummer-Vinson syndrome, and frequent consumption of very hot beverages. Rarely, HPV infection may also be implicated in some SCC.

Approximately one half of squamous cell carcinomas are located in the middle third of the esophagus. The tumors can cause a stricture, with associated symptoms of dysphagia, odynophagia (pain on swallowing), and obstruction. Some patients with advanced invasive disease present with food aspiration via a tracheo-esophageal fistula.

Staging is based on tumor invasiveness, presence of lymph node metastases, and distant metastases (T, N, M).


Vitamin E

Vitamin E includes. . .
tocopherols, with saturated 16 carbon acyl chains
tocotrienols, with polyunsaturated 16 carbon acyl chains

Abundant in plant oils, e.g. palm oil, sunflower oil, canola oil, wheat germ

Vitamin E digestion and absorption parallels fat digestion and absorption.

Vitamin E functions in lipid bilayers in intracellular and plasma membranes. The phenolic hydroxyl can distribute and stabilize singlet oxygen and free radicals as part of cellular oxidative stress defense.

Vitamin E, when oxidized, can be regenerated by ascorbate (vitamin C).

Vitamin E inhibits Vitamin K absorption and metabolism.

Deficiency is rare except in people with absorption problems, e.g. premature infants, Crohns, short bowel syndrome. Also can occur with inherited lipoprotein disorders.

hemolytic anemia
peripheral neuropathy
ataxia, loss of vibratory sense

not toxic


Vitamin K

Phylloquinone is the main form of Vitamin K in the diet. It is abundant in leafy green vegetables.

Menaquinones have variable numbers of isoprenoid subunits on the acyl chain. They are produced by fermentation. (In gut, in cheese.)

Menadione is a synthetic Vitamin K used in animal feed.

Vitamin K digestion and absorption parallels fat digestion and absorption

Vitamin K is stored in cellular membranes, especially the lung, kidney, bone marrow, and adrenal glands.

In target cells, Vitamin K acts as a cofactor for g-glutamyl carboxylase. This enzyme carboxylates glutamic acid side chains on blood clotting proteins.

Factor IX (Christmas factor), Factor VIIa, Factor X (Stuart factor), and prothrombin are dependent on Vitamin K dependent carboxylation.

Vitamin K deficiency:
Rare; most people get adequate Vitamin K.

Can occur in infants (milk is low in Vitamin K), people with absorption disorders.

Severe deficiency manifests as coagulation disorder: increased prothrombin time, increased bleeding.

not toxic


Vitamin D

Vitamin D is found primarily in food of animal origin such as liver, eggs, fatty fish. It is also present in shitake mushrooms, and is fortified in many dairy products.

Vitamin D can be synthesized de novo from cholesterol. To make the active Vitamin D3, metabolism of skin, liver, and kidney is required.

Vitamin D’s most important function is to regulate calcium homeostasis, but it may play other beneficial roles.

The dietary form of Vitamin D, cholecalciferol, is absorbed through passive diffusion with fat into intestinal epithelial cells. It is transported to tissue in chylomicrons, and taken up by the liver in chylomicron remnants

The hydroxylation to make the biologically active 1,25-dihydrocholecalciferol (1,25-OH D3) occurs in the kidney in response to parathyroid hormone (PTH).

PTH is produced by the parathyroid in response to low calcium concentrations.

The vitamin D receptor (VDR) acts as a ligand activated transcription factor.

Activated VDR increases expression of the calcium channel TRPV6 at the brush border, calbindin in the cytoplasm, and calcium ATPase pumps at the basolateral membrane.

VDR also alters tight junction permeability to calcium.

Vitamin D deficiency

Rickets, characterized by seizures, growth retardation, failure of bone mineralization (osteomalacia).

Vitamin D deficiency can be dietary, genetic, or secondary to an absorption problem such as Crohns.

Vitamin D toxicity

Vitamin D is the most likely vitamin to have toxic effects.

The TUL is 4,000 IU for age 9+

Toxic effects begin when serum 25-OHD3 > 500 ng/mL
calcification of soft tissues (kidneys, heart, lungs, blood vessels)
hyperphosphatemia, hypertension

Summary: The vitamin D receptor physically interacts with b-catenin, preventing its transactivation of genes that promote cellular proliferation.



four human enzymes require it sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase



Role in insulin sensitivity, binds chromodulin, an insulin receptor binding protein



Role in antioxidant proteins; de-iodinases in the thyroid: Selenocysteine



Thyroid hormone



Major functions:
Bone mineralization
Blood clotting
Muscle contraction
Metabolism regulator


Saturable carrier mediated transport:
TRPv6 transports Ca2+ across the brush border membrane
Calbindin chaperones Ca2+ within the cell
Ca2+ /ATPase transports Ca2+ across the basolateral membrane

Pericellular transport around tight junctions: Claudin

Increases Ca2+ absorption:
Vitamin D
sugars; sugar alcohols

Decreases Ca2+ absorption:
Phytic, oxalic acids
Other divalent cations, e.g. Mg2+ & Zn2+
Unabsorbed fatty acids

Activated VDR increases expression of the calcium channel TRPV6 at the brush border, calbindin in the cytoplasm, and calcium ATPase pumps at the basolateral membrane.
VDR also alters tight junction permeability to calcium.

The cytosolic concentration of Ca2+ is very low (100 nmol).
The extracellular concentration of Ca2+ is 10,000x higher (2.3 mmol).
Ca2+ is stored in intracellular compartments, e.g. mitchondria, ER

Export of Ca2+ from cells:

Ca2+ /3Na+ exchanger is a low affinity, high capacity transporter
Ca2+ /2H+ exchanger is a high affinity, low capacity transporter

Intracellular signaling by calcium is mediated by calmodulin, a protein whose association with other proteins is regulated by calcium binding.

When intracellular calcium increases, glycogen synthase is inactivated and glycogen phosphorylase is activated

Interactions with other dietary components:

Calcium blocks phosphorous uptake
High doses of Ca2+ used to treat hyperphosphatemia secondary to kidney failure.

Calcium transiently blocks iron uptake

Calcium can trap fatty acids and bile salts in ‘soaps’ that are not digestable.
Bile salts are not recycycled
Cholesterol is diverted to bile acid synthesis
decreased chenodeoxycholate in bile
LDL decreases

Resorption in the proximal tubule is controlled by calcitriol.
Caffeine increases urinary excretion of calcium.
Sodium and calcium share common resorption mechanism in the proximal tubule. Very high sodium inhibits calcium reuptake and increases excretion.

Acute toxicity:
constipation, bloating

Chronic toxicity:
hypercalcemia can cause calcification of soft tissue
may lead to hypercalciuria and kidney stones



Magnesium rich foods include nuts, legumes, whole grains, chlorophyll, chocolate, and ‘hard’ water.

Saturable transport across brush border: TRPM6

Basolateral transport:
2Na+/Mg2+ antiporter

Non-saturable paracellular diffusion.

70% of bone magnesium is associated with phosphorous and calcium in crystal lattice.
30% of bone magnesium is in amorphous form on the surface; this is available for exchange with serum to maintain magnesium homeostasis.

Intracellularly, >90% of magenesium is associated with ATP.
Magnesium is essential for kinases and polymerases that use nucleotide triphosphates.

Activation of vitamin D requires magnesium.

Interactions with other things in the diet:

Vitamin D

Mg2+ may mimic Ca2+ and compete for resorption in the kidney.

Mg2+ inhibits phosphorous absorption by forming Mg3(PO4)2 precipitate.

Serum is a minor store of magnesium, so concentrations are not reliable.

Erythrocyte magensium is not turned over as rapidly, and can be a better measure.

Renal Mg2+ excretion before and after a loading dose is the best measure of magnesium status.

Gitelman syndrome is an autosomal recessive mutation of SLC12A3, a thiazide sensitive Na/Cl transporter characterized by hypomagnesemia, hypokalemia, hypocalciuria.

Toxicity associated with use of epsom salts (MgSO4).
Symptoms are diarrhea, dehydration, flushing, slurred speech, muscle weakness, loss of deep tendon reflex.



Chloride is absorbed paracellularly, or through a Na+/Cl- electroneutral transporter.

Chloride is the only anion secreted by gastrointestinal cells.

Chloride enters red blood cells in exchange for bicarbonate when cells deliver oxygen to tissues.
when bicarbonate goes out, chloride goes in to balance charge

Hypochlorous acid (~ bleach) is secreted by neutrophils during phagocytosis to neutralize pathogens.

Gastric hydrochloric acid secretion by parietal cells.



In the diet: Fruit, leafy green vegetables, milk

Paracellular diffusion
K+/H+ ATPase

K+ channel

Potassium functions as the major intracellular cation.
It functions to generate and maintain electrical potential across cell membranes.
Na+/K+ ATPases consume energy to accumulate potassium within cells.
Channels then allow potassium to flow out of the cell, resulting in a loss of positive charge.

The major intracellular cation.
Muscle contractility (smooth, skeletal, cardiac)

Vasopresin and aldosterone increase urinary potassium excretion.
Opposite of sodium.

Potassium decreases calcium excretion (opposite of sodium).




Phosphorous is widely distributed in the diet: Meat, poultry, fish, eggs, dairy, cola (phosporic acid).

Inorganic (phosphates)
Organic: associated with protein, sugar, lipids, nucleic acids
Phytic acid: limited bioavailability

Saturable carrier mediated active transport is used when phosphate intake is low. It is activated by calcitriol.
Diffusion occurs in the proximal duodenum (slightly acidic and phosphate is in the H2PO4- form).

Phosphorous absorption is inhibited by:
Magnesium ( Mg3(PO4)2 is un-absorbable.)

Functions of phosphorous:

Bone mineralization:
amorphous: Ca3(PO4)2, CaHPO4-2H2O, Ca3(PO4)2-3H2O
crystalline: hydroxyapatite: Ca10(PO4)6(OH)2

calcitonin  phosphorous deposition in bone
calcitriol  phosphorous desorption from bone

Molecules with high energy bonds:
Nucleic acids: DNA, RNA
Proteins: Serine, Threonine, Tyrosine
Vitamins  cofactors
thiamin  thiamine pyrophosphate (TPP)
pryidoxine  pyridoxal phosphate (PLP)

Acid base balance: Na2HPO4 + H+  NaH2PO4 + Na+
Phosphorous is an important buffer in the kidney.

Availability of oxygen: 2,3-bisphosphoglycerate

Regulation of phosphorous is at the level of renal clearance.

Excretion of phosphorous is promoted by:
elevated dietary phosphorous
parathyroid hormone (PTH)
phosphotonins (e.g. FGF-23; secreted by osteoblasts and osteocytes)

Excretion of phosphorous if inhibited by:
low dietary phosphorous
thyroid hormone
growth hormone

Phosphorous deficiency is rare, but can occur in. . .

Extreme use of antacids containing magnesium, calcium, aluminum
Refeeding syndrome
Inherited disorders:
Dents disease: X-linked, mutation in renal chloride channel
X-linked hyphosphatemic Rickets: Mutation in PHEX gene causes elevated FGF-23
Autosomal dominant hypophosphatemic Rickets: Mutation in the gene encoding FGF-23, prevents its degradation.

Deficiency symptoms:
anorexia, reduced cardiac output, decreased diaphragmatic contractility, myopathy, death



At the brush border, a reductase reduces ferric iron to ferrous iron.
Fe2+ then is transported through the divalent metal transporter -1 (DMT1).

Within the cell, iron is stored bound to ferritin (a protein).

Iron transport in the blood requires oxidation to Fe3+ by hephaestin (HP; ceruloplasmin). This is a copper requiring enzyme.

Fe3+ then binds transferritin for transport to tissues.

Regulation of iron uptake is through hepcidin. When iron stores in the liver are high, hepcidin is produced. It binds ferroportin (FPN) and causes its degradation.

Iron-Sulfur clusters:
Electron transfer groups in, e.g. NADH dehydrogenase

Iron interactions:
Vitamin C enhances absorption and maintains iron in the reduced state.
Copper is required for export from enterocytes.
Iron inhibits zinc absorption.

Iron deficiency
Observed in
infants (low iron in diets)
adolescents (rapid growth rate)
pregnant women (rapid growth rate, blood loss at delivery)
absorption disorders
Symptoms: Microcytic hypochromic anemia, listlessness, fatigue

Iron toxicity: TUL = 45 mg / day
If intake exceeds the livers ferritin storage capacity, it can accumulate in tissues and act as a free radical, causing oxidative damage.
Chronic hemochromotosis is caused by inherited mutations in hepcidin (or other iron metabolism genes). It causes organ failure due to iron accumulation.



In the diet, copper is found in meat, shellfish, and nuts

A brush border reductase reduces Cu2+ to Cu+.
Cu+ then is transported through CTR1.
Cu+ can then enter the blood through ATP7A, a basolateral transporter, and circulate bound to proteins e.g. albumin.

Menkes kinky hair syndrome is caused by mutations in ATP7A. It is characterized by hypothermia, hypotonia, poor feeding, failure to thrive, and seizures.

Patients have normal hair at birth, but it becomes brittle and sparse as they age.

Copper functions:
Cofactor for ceruloplasmin; see iron.
Cytochrome C oxidase has 3 Cu+ per enzyme
Cofactor for lysyl oxidase (collagen synthesis; also requires ascorbate
Copper is a cofactor for superoxide dismutase, an antioxidant enzyme
Copper is a cofactor for dopamine b-hydroxylase, required for catecholamine synthesis

Copper deficiency:
May occur in people who consume a lot of zinc, or a lot of proton pump inhibitors.
Symptoms: anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism.

Copper toxicity: TUL = 10 mg/day
acute: epigastric pain, nausea, vomiting, diarrhea
chronic: hematuria, liver damage, kidney damage
Wilson disease is caused by mutation in the liver specific copper transporter ATP7B.


Wilson disease

caused by mutation in the liver specific copper transporter ATP7B.

ATP7B normally transports excess copper into the bile for excretion. When it is defective, copper accumulates and ‘leaks out’ unbound to ceruloplasmin.

Treatment is to avoid high copper foods, and chelation therapy.


Pancreas divisum

results from failure of fusion of the fetal dorsal and ventral pancreatic ducts. As a result, the bulk of the pancreas drains through the dorsal pancreatic duct and the small caliber minor papilla (see image). This is the most common congenital anomaly of the pancreas, affecting 7% of individuals. It is almost always asymptomatic, but in some cases can be associated with chronic pancreatitis, perhaps secondary to relative stenosis caused by the bulk of secretions passing through the minor papilla.


Annular pancreas

defined as a band-like ring of normal pancreatic tissue that completely encircles the second portion of the duodenum. Often associated with other congenital anomalies. May cause duodenal obstruction.



The anatomic changes of acute pancreatitis are secondary to autodigestion of the pancreatic tissue by inappropriately released, activated pancreatic enzymes.

The basic morphologic alterations are microvascular leakage causing edema, necrosis of fat by lipolytic enzymes, acute inflammation, proteolytic destruction of pancreatic parenchyma, and destruction of blood vessels and subsequent interstitial hemorrhage.

Mild forms of acute pancreatitis demonstrate interstitial edema, focal fat necrosis, and mild acute inflammation (acute edematous (interstitial) pancreatitis). In severe cases, there is also necrosis of the pancreatic parenchyma, often with hemorrhage (acute hemorrhagic necrotizing pancreatitis). Fat necrosis can also be found in extrapancreatic fat (e.g. omentum, small bowel mesentery). Calcium can precipitate in the areas of fat necrosis, resulting in hypocalcemia.


Chronic pancreatitis

is defined as inflammation of the pancreas with irreversible destruction of the exocrine parenchyma, fibrosis, and in the late stages, destruction of the endocrine parenchyma.

Repeated acinar cell injury leads to the production of fibrogenic cytokines (TGF-beta and PDGF) that result in myofibroblast proliferation, collagen secretion, and remodeling (fibrosis) of the extracellular matrix. Pancreatic insufficiency occurs due to irreversible loss of acinar tissue.

Morphologically, parenchymal fibrosis is seen, with reduced number and size of acini with (initially) relative sparing of the islets, and variable dilation of the pancreatic ducts.

Type I autoimmune pancreatitis is characterized by a lymphocytic sclerosing pancreatitis with increased IgG4 producing plasma cells. This form of pancreatitis may form a mass and mimic pancreatic cancer. It is important to recognize this entity as it is generally responsive to steroid therapy. This type of pancreatitis is now considered to be a manifestation of IgG4-related disease.


Skeletal muscle of pharynx and upper esophagus derived from

Skeletal muscle of pharynx and upper esophagus derived from branchial arch mesoderm (4th & 6th arches).


Serous (microcystic) cystadenoma

rare, benign cystic neoplasm composed of glycogen-rich cuboidal cells surrounding small (1-3 mm) cysts containing clear, thin, straw-colored fluid. Accounting for about 25% of pancreatic cystic neoplasms, this tumor typically occurs in older adults, and patients may present with abdominal pain. Surgical resection is usually curative.


Mucinous cystic neoplasm

can be benign (mucinous cystadenoma) or malignant with tissue invasion (mucinous cystadenocarcinoma). These tumors typically occur in middle aged women (95%). In contrast to microcystic cystadenoma, these tumors form large multiloculated cysts filled with mucin. The tumors arise in the tail or body of the pancreas, do not communicate with the pancreatic duct, and present as a painless slow-growing mass. Treatment is with surgical resection (often distal pancreatectomy) and careful histologic assessment to determine if an invasive, malignant component is present.


Intraductal papillary mucinous neoplasm

Defined as a papillary mucinous neoplasm arising in the pancreatic ducts.

Can affect both men and women, usually older adults. IPMNs involve the head of the pancreas more often than the tail. This neoplasm is multifocal in 10-20% of cases.

Unlike mucinous cystic neoplasms, this tumor communicates with the pancreatic duct system and lacks the “ovarian type” stroma.

IPMN can be benign, or malignant when tissue invasion is present. Benign IPMNs can demonstrate varying degrees of dysplasia. Thus benign IPMNs can be a precursor to pancreatic adenocarcinoma.

Grossly, the duct system is dilated, reminiscent of bronchiectasis. In some cases, the papillary tumor can be seen within the ducts.


Pancreatic exocrine carcinoma:

Most common pancreatic neoplasm, and the fourth leading cause of cancer deaths.

Almost all are ductal adenocarcinomas.

Most pancreatic ductal carcinomas arise from dysplastic non-invasive precursor lesions in small ducts referred to as pancreatic intraepithelial neoplasia (PanIN). There is a progression from non-neoplastic ductal epithelium to pancreatic intraepithelial neoplasia (PanINs) to invasive ductal adenocarcinoma. This progression is accompanied by chromosomal and molecular alterations, including mutations involving activation of oncogenes (e.g. KRAS), and inactivation of tumor suppressor genes (e.g. CDKN2A, SMAD4, p53). Some tumor suppressor genes are silenced by hypermethylation of the promotor regions. Genetic progression is also seen in the pancreatic adenocarcinomas that arise from IPMNs.

Risk factors for the development of pancreatic carcinoma include cigarette smoking, obesity and physical inactivity, diabetes, chronic pancreatitis, family history (5-10% of patients with pancreatic cancer have had a first degree relative with the disease), specific inherited predispositions (see chart), and hereditary pancreatitis.

Most cases of pancreatic carcinoma (80%) occur over the age of 60.

Most common location is the head of the pancreas (60%), followed by the body (15%) and tail (5%); 20% of tumors exhibit diffuse pancreatic involvement.


Dorsal mesogastrium

suspends the distal esophagus, stomach, and proximal duodenum from the dorsal wall.


Pancreatic neuroendocrine (endocrine) neoplasms

These tumors typically occur in adults, and are sometimes associated with MEN (multiple endocrine neoplasia) syndromes.

Can occur anywhere in the pancreas, but most are found in the body or tail of the pancreas. The tumors can also occur in the peripancreatic tissues.

Tumors are usually well-circumscribed, as opposed to pancreatic exocrine carcinoma (remember this!). They may be solitary or multiple. Functioning tumors are usually smaller than non-functioning tumors.

Metastases, when present, typically occur in peripancreatic lymph nodes and liver. Even with metastases, patients may have a prolonged clinical course, in contrast to pancreatic exocrine (ductal) carcinoma.

Functioning tumors can produce clinical syndromes based on hormone secretion.



Virtually always associated with cholelithiasis.

Some cases are secondary to repeated bouts of acute cholecystitis, but most are not. Supersaturated bile may lead to chronic inflammation as well as to the formation of gallstones.

Pathology: gallbladder exhibits varying degrees of chronic lymphocytic inflammation and fibrosis.

Dystrophic calcification of the gallbladder wall can occur, producing so called "porcelain gallbladder."



subepithelial accumulations of lipid-laden macrophages, which grossly appear as yellow mucosal flecks. Cholesterolosis is due to excessive accumulation of cholesterol from supersaturated bile, and has no clinical significance.



usually located at the fundus, this lesion consists of gallbladder diverticulae with focal muscular hypertrophy of the gallbladder muscle wall. This lesion is not a true neoplasm, and appears as an intramural thickening of the fundic wall of the gallbladder.



90% of patients are over the age of 50.

Typically associated with cholelithiasis (95%).

Pathogenesis may be related to irritative trauma or chronic inflammation; derivatives of bile acids may also be carcinogenic.

Some cases may be associated with a pre-existing gallbladder adenoma.

Only 1-2% of patients with gallstones develop gallbladder carcinoma. In most cases, the tumor is discovered incidentally, as a result of surgery for gallstone disease.

In most cases the tumor has spread centrifugally directly to the liver or metastasized to regional lymph nodes by the time symptoms appear (this is a “silent tumor” like pancreatic carcinoma). The 5 year survival rate is very low (10%).



Relatively uncommon tumors (3% of cancer deaths in USA).

Most cases occur over the age of 50.

Klatskin tumor refers to a cholangiocarcinoma arising at the confluence of the right
and left hepatic ducts at the liver hilus (perihilar cholangiocarcinoma).

Tumors of the ampulla of Vater include tumors arising from the duodenal mucosa,
pancreatic duct, and bile duct and are collectively referred to as periampullary

Extrahepatic cholangiocarcinomas are associated with those conditions resulting in chronic cholangitis, such as infection with liver flukes (Opisthorchis and Clonorchis), PSC, and choledochal cysts. Stone disease is present in only 35% of cases. Many cases have no disease associations.

Patients usually present with painless jaundice secondary to obstruction (very similar to pancreatic cancer presentation).

Typically see a cholestatic injury pattern with increase in alkaline phosphatase, GGT.

Diagnosis requires demonstration of obstructing lesion and tissue biopsy or cytology indicating malignancy (CT scan, endoscopy with EUS and FNA, ERCP with cytology brushings and biopsy, surgical biopsy).

Overall survival is very poor, with only rare long term survivors; survival better with ampullary tumors (25%).



Hormone gastrin is secreted from G cells in the antrum, which activates parietal cells in the fundus/corpus to secrete acid

Gastrin is polypeptide with variable length and sequence that binds to CCK2 receptors

Triggers for Gastrin release from G cells in the antrum1. Seeing food or stomach distension causes vagal stimulation causing release of Gastrin-releasing peptide2. Aromatic amino acids in the lumen

Gastrin, histamine (H2), and ACh activate acid secretion of parietal cells via cAMP or Ca++ dependent pathways

Inhibitor of gastrin release - Somatostatin is secreted from D cells in the antrum when pHDuring gastric phase, food enters the stomach raising the pH leading to a decrease in somatostatin secretion and an increase in Gastrin levels


Major stimulants of Gastric Acid Secretion

Acetylcholine, the neurotransmitter released from vagal fibers and enteric neural excitatory fibers:
Binds muscarinic receptors on parietal cells

Gastrin released into the blood by G cells
Binds to parietal cells
Activates ECL cells release of histamine

Histamine released from ECL cells binds parietal cells.


Inhibitors Gastric Acid Secretion

Somatostatin when pH


Phases of Gastric Secretion

Interdigestive Phase: Low acid secretion, D cells secrete somatostatin to maintain low levels of Gastrin

Cephalic Phase – dorsal vagal complex integrates input from higher centers (seeing and tasting food) to activate Vagus nerves. GRP activates gastrin release and Ach activates ECL and parietal cells.

Gastric Phase – distension of the stomach activates vagal afferents and the enteric nervous system. Amino acids activate gastrin secretion and food raises pH decreasing somatostatin secretion.

Intestinal Phase – introduction of the gastric contents into the small intestine activates duodenal G cell secretion of gastrin. Activation of secretin and other enterogastrones and neural reflex decreases gastric secretion.



Pepsinogen is a group of inactive proenzyme proteases.

Secreted by Chief Cells in gastric glands in response to acetylcholine and gastrin… inhibited by secretin

Activated by acidic environment of stomach to pepsin which is a potent proteolytic enzyme.

Pepsin is an endopeptidase and further activate pepsinogen by autolysis.

Chief cells also secrete gastric lipase, which releases fatty acids.


Zollinger-Ellison Syndrome

Usually caused by a Gastrin-secreting tumor in the pancreas or small intestine
Results in excess H+ secretion as well as hyperplasia and hypertrophy of parietal cells
95% of patients develop gastric ulcers

Caused by gastrin secreting tumors which are most commonly found in the pancreas and small bowel.

Elevated gastrin (diagnostic test) results in marked increase in the number of parietal cells, with increased gastric acid production. In addition, there is hyperplasia of mucus neck cells with mucin hyperproduction, and proliferation of endocrine cells in the stomach which can result in gastric carcinoid tumors.

Patients will often present with PUD or chronic diarrhea. Treatment consists of removal of the gastrinoma and administration of proton-pump inhibitors.

Gastrinomas are sporadic in 75% of patients, and the remainder are associated with MEN type I. The sporadic tumors tend to be solitary, whereas those associated with MEN type I may be multiple. Overall, 60-90% of gastrinomas exhibit malignant behavior.


Intestinal influences on gastric motility

Gastric contractions and gastric emptying are inhibited by:-

acid in the duodenum via neural (enteric and vagal) and hormonal (secretin and somatostatin) mechanisms-

fat in the duodenum via hormonal (CCK) mechanisms and via enteric neural mechanisms-

osmolality of the duodenal contents via enteric neural mechanisms and perhaps hormonal mechanisms (GIP)



reduced gastric emptying often due to diabetic neuropathy involving the vagus and enteric nerves in the stomach such that the stomach fails to generate enough force to empty the stomach. Other causes include drugs and cancer treatments. Results in nausea, vomiting, bloating, poor digestion, weight loss, malnutrition, impaired absorption of medications, and impaired glycemic control. Treat with prokinetic drugs.


Dumping Syndrome

rapid gastric emptying often resulting from gastric bypass surgery, vagotomy, and high sugar-containing meals. Rapid entry of gastric contents into the duodenum represents an osmotic challenge, water moves into the lumen resulting in hypovolemia and reduced blood pressure. Results in nausea, weakness, dizziness, sweating, shakiness, diarrhea, heart palpitations


Peptic ulcer disease

scarring and ulcers near the pylorus can delay emptying or in duodenal ulcers can lead to rapid gastric emptying due to loss of duodenal negative
feedback mechanisms.


Streptococcus mutans

Gram (+)
Cocci (beads on a string)
Catalase negative
Facultative anaerobic
Hemolytic (Viridins group)
Optochin Resistant

adhesin-like surface-associated proteins (e.g. AgI/II family) that are capable of binding to receptors in the pellicle

extracellular glucosyltransferases (Gtfs) are constituents of the pellicle and are capable of synthesizing glucans (a type of polysaccharide) in situ from sucrose. Glucans provide additional S. mutans binding sites, as it binds avidly and in large numbers to these polymers


Porphyromonas gingivalis

Gram (-)
Black-pigmented colonies on blood agar plates
Bacitracin resistant


Candida albicans

Oral Thrush
Most common in babies, elderly, immunocompromised
Grows both as a yeast and as filamentous cells, can form spores given the right conditions
Esophageal form is dangerous

Diagnosis: May diagnose entirely on symptoms, but scraping on microscope slide can be performed (look for hyphae forms)

Treatment: Must treat with prescription antifungal
Most commonly a topical treatment: clotrimazole lozenge and nystatin suspension (swish and swallow).
Unresponsive cases: a systemic antifungal such as fluconazole
Worst case: IV administration of amphotericin B (significant side effects)



Hairy leukoplakia
Fuzzy white patches on side of tongue
Unlike thrush, it cannot be wiped away



Ludwig’s angina

Skin infection on floor of the mouth, usually results from untreated dental infections.
Swelling of infected area may block the airway or prevent swallowing of saliva.

Symptoms include:
Breathing difficulty
Confusion or other mental changes
Neck pain
Neck swelling
Redness of the neck
Weakness, fatigue, excess tiredness


H. pylori

Gram (-)
Flagellated helix-shaped rod (spirilli)
Catalase and oxidase (+)
Urease (+)

VacA: Pore forming cytotoxin that allows leakage of Ca+ from epithelial cell

CagA: Type 4 secretion system (TFSS) is a needle through which CagA travels into the host cytosol and affects the proliferative activities, adhesion, and cytoskeletal organization of epithelial cells. The entire system is also highly proinflammatory.


Breath test

Detects radioactive CO2
Good for diagnosis
Good for confirming cure
Requires skilled technician


Blood test

Detects H. pylori antibodies
Useful for initial diagnosis only
Not useful for confirming cure


Stool antigen test

Good for diagnosis
Good for confirming cure


Autoimmune gastritis

Due to autoimmune CD4+ T-cell mediated destruction of parietal cells; chief cells are also lost during destruction of the gastric glands (“bystander damage”). Antibodies to parietal cells and intrinsic factor are also produced as part of the autoimmune response, but are not pathogenic (can be used as a diagnostic test).

The autoimmune damage results in:
Decreased gastric acid secretion (achlorhydria).
Compensatory hypergastrinemia and hyperplasia of antral gastrin-producing G cells, along with endocrine cell hyperplasia in the fundus and body of the stomach.
Vitamin B12 deficiency due to loss of secreted intrinsic factor (pernicous anemia with increased RBC MCV).
Reduced serum pepsinogen I concentration.
Inflammatory mucosal damage and atrophy of the gastric mucosa in the body and fundus with sparing of the antrum and cardia.

Clinical findings develop after many years and are related to vitamin B12 deficiency


Chronic reactive gastropathy

Pattern of chronic gastric injury characterized by foveolar hyperplasia, mucin depletion, vascular congestion, edema, and lamina propria fibrosis. Changes are due to chemical mucosal injury, associated with use of NSAIDs, aspirin, bile reflux, and alcohol ingestion. Patients can get gastric erosions and ulceration.

Chronic reactive gastropathy is very common, so make sure you understand the implications when a gastric biopsy is signed out as “gastritis with changes of chronic reactive gastropathy.”


Peptic ulcer disease

Chronic ulceration of the GI tract associated with exposure to gastric type acid, typically occurring in the stomach and first portion of the duodenum (duodenum most common site).

Most cases are due to either H. pylori chronic gastritis or due to chronic use of NSAIDs. H. pylori can produce hyperchlorhydric chronic gastritis which then damages the mucosa. NSAIDs cause direct chemical irritation and can suppress prostaglandin synthesis which is necessary for mucosal protection. It is estimated that 70% of patients with PUD have H. pylori infection, although only about 20% of H. pylori infected individuals will develop PUD.

Other causes of ulceration associated with exposure to gastric acid include Zollinger-Ellison syndrome, GERD (with esophageal ulceration), and heterotopic gastric mucosa in a Meckel’s diverticulum (small intestinal ulceration). Other factors implicated in ulceration include cigarette smoking, and chronic use of high dose corticosteroids.

Complications of chronic ulceration in PUD include:

Bleeding (clinical hemorrhage as well as iron deficiency anemia).


Obstruction, particularly when the ulcer is located in the pyloric channel, secondary to edema and fibrosis.

Clinically, patients present with epigastric burning or aching pain, (often occurring 1-3 hours after eating and relieved with food), GI bleed, iron deficiency anemia, or perforation.

Treatment is eradication of H. pylori if present, and neutralization of gastric acid with proton-pump inhibitors. Limiting use of offending medications such as NSAIDs is also recommended. Perforated ulcers can produce free air in the abdomen which can be seen on upright radiographs. These perforated ulcers may require surgical treatment.


Eosinophilic gastritis

defined as eosinophil rich inflammation, in the absence of a known cause for eosinophilia (e.g. reaction to drugs, parasitic infections, malignancy).

Most cases are thought secondary to some type of allergic reaction to a food allergen (e.g. cow’s milk or soy protein in children). Patients may have peripheral blood eosinophilia and elevated IgE levels.

Isolated eosinophilic gastritis is rare; most cases have involvement at multiple GI sites (e.g. esophagus, duodenum, in addition to the stomach – “eosinophilic gastroenteritis” when small bowel and stomach are involved).

Lesions may present as a mass, large ulcer, or with pyloric obstruction.


Lymphocytic gastritis

gastritis characterized by marked intraepithelial lymphocytic inflammation (CD8+ T lymphocytes). Can be seen as an isolated finding, or in patient’s with either co-existing celiac disease or in patients with co-existing lymphocytic/collagenous colitis.


Collagenous gastritis

gastritis that appears morphologically similar to collagenous colitis. It can occur in patients with co-existing collagenous colitis, and also as an isolated disease involving the stomach only


Granulomatous gastritis

defined as gastritis with granulomatous inflammation. Most cases are secondary to an underlying disorder, such as Crohn’s disease, sarcoidosis, mycobacterial or fungal infections.


Menetrier’s disease

Very rare disorder caused by excessive secretion of transforming growth factor alpha (TGF-α). This results in marked diffuse hyperplasia of the foveolar epithelium of the body and fundus of the stomach. Patients also experience protein losing enteropathy and hypoproteinemia, with diarrhea, weight loss, and peripheral edema. Some cases of Menetrier’s disease are associated with an infection (e.g. CMV in children).

Patients are also at risk for gastric adenocarcinoma.


Hyperplastic polyp

Most occur in association with chronic gastritis (H. pylori gastritis, chronic reactive gastropathy, autoimmune gastritis); 75% of all gastric polyps are of this type, and most occur in the gastric antrum, followed by the body. These polyps may represent an exaggerated mucosal response to tissue injury and inflammation. Rarely, dysplasia and adenocarcinoma can develop in hyperplastic polyps.


Cystic fundic gland polyp

Most occur in association with the use of proton pump inhibitors, secondary to increased gastrin secretion in response to decreased gastric acid. These polyps can also be seen in individuals with familial adenomatous polyposis (FAP).


Gastric adenoma

Neoplastic polyp morphologically similar to other adenomas found in the GI tract (e.g. colon). Incidence of gastric adenomas increases with age, with most occurring in patients age 50 years and older. Gastric adenomas are also increased in incidence in patients with FAP.

Since gastric adenomas often occur in association with chronic gastritis and intestinal metaplasia, some believe they represent polypoid areas of dysplasia.


Inflammatory fibroid polyp

Mesenchymal polypoid proliferation composed of a mixture of stromal spindle cells, small blood vessels, and inflammatory cells, particularly eosinophils.

Can occur anywhere in the GI tract but stomach and small intestine are the most common sites.

Usually occur in middle aged females, and are felt to represent a reactive “pseudotumor.”


Pancreatic heterotopia

ectopic pancreatic rests in the stomach can produce a polypoid lesion.


Gastric xanthoma

consist of small,
sessile, yellow mucosal nodules
composed of aggregates of
lipid laden macrophages in the
lamina propria. Most commonly
seen in chronic gastritis, and
may represent a reaction to
tissue injury.


Congenital hypertrophic pyloric stenosis

Stenosis is due to hyperplasia of the pyloric muscularis propria. Occurring in 1 of 300 to 900 live births, it is 3-4 times more common in males. Patients typically present in the second or third week of life with new-onset regurgitation and persistent, projectile, non-bilious vomiting. Physical examination may reveal a firm abdominal ovoid mass. Surgical myotomy is curative.


Dieulafoy’s lesion

Unusually large-diameter mural arteriole penetrates into the submucosa; these large vessels can erode through the mucosa and cause massive bleeding


Gastric adenocarcinoma

Most common malignancy of the stomach (90%).

Significant variation in incidence worldwide, with countries such as Japan having 4-fold higher incidence than North America. This is believed to be secondary to environmental influences.

In USA, incidence of gastric cancer has declined dramatically in the 20th century, perhaps because of reduced intake of possible dietary carcinogens as well as decreased H. pylori prevalence (see chart).

Risk factors for gastric adenocarcinoma include:
-Chronic gastritis, such as H. pylori gastritis and autoimmune gastritis (intestinal metaplasia-dysplasia-carcinoma sequence).
-Dietary carcinogens (nitrosamines, smoked foods).
-Menetrier’s disease.
-Diets lacking in fruits/vegetables (antioxidants).
-Patients with familial adenomatosis polyposis (FAP).

Patients often present with symptoms of dyspepsia, dysphagia, and nausea (like chronic gastritis). Gastric adenocarcinomas typically occur in adults. Most adenocarcinomas involving the stomach occur at the GE junction, but these tumors are usually considered to be distal esophageal adenocarcinomas if their epicenter is within 5 cm of the GE junction and there is extension into the distal esophagus (typically see Barrett’s esophagus with these). Thus, most true gastric adenocarcinomas occur in the antrum.

Morphologic types:

Intestinal type: can present as a polypoid invasive mass or invasive ulcer. Microscopically, tumor shows glandular differentiation.

Diffuse type: presents as diffuse involvement and thickening of the gastric wall (mucosa, submucosa, and muscularis propria). Microscopically, see signet-ring cells. Sometimes, this type of tumor can occur in younger adults. Diffuse involvement of the gastric wall can produce rigidity and a leather bottle appearance (linitis plastica).

Treatment is with surgery, including regional lymph node dissection. Chemotherapy is used for those with unresectable disease and/or metastases. Overall survival is poor, with 5-year survival rate of 20%.


Gastrointestinal stromal tumors (GIST)

Can arise anywhere in the GI tract, but stomach is the most common site (60% stomach, 30% jejunum and ileum, 5% duodenum,


Gastric lymphomas

Stomach can be involved by a variety of lymphomas, but the most common lymphoma is the extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma, also known as MALTomas), followed by diffuse large B-cell lymphoma (DLBCL).

MALT lymphomas can arise in virtually any mucosal site (e.g. lung, GI tract, salivary gland, with stomach the most common site) and are typically associated with chronic inflammation. In the stomach, most MALT lymphomas are associated with H. pylori infection. It is believed that persistent infection with chronic antigenic stimulation results in activation of transcription factors that promote B-cell growth and survival. In some cases this is due to specific translocations resulting in fusion genes with transcription activation. In other cases, persistent H. pylori antigenic stimulation can activate transcription and induce a MALT lymphoma without genetic translocations.

Importantly, eradication of H. pylori infection with antibiotics will cause regression of gastric MALT lymphoma in 60-90% of cases! Gastric MALT lymphomas due to translocations are associated with a lack of response to antibiotic therapy.

As with H. pylori infection, patients present with dyspepsia and epigastric pain. Diagnosis is established by findings on the biopsy.



Obstruction can also be caused by ileus, which is loss of the normal propulsive function of the bowel in the absence of mechanical obstruction (intestinal pseudo-obstruction). Ileus can be associated with a variety of conditions, such as a complication of abdominal surgery, abdominal trauma, peritonitis, mesenteric ischemia or infarction, use of medications (e.g. narcotics), intra-abdominal infection, and as a complication of gastroenteritis (not a complete list by any means).



Defect in the wall of the peritoneal cavity, permitting protusion of a serosal lined pouch of peritioneum called a hernia sac. Most common location for acquired hernias is the inguinal or femoral canal, umbilicus, or at sites of abdominal surgical scars. Visceral protusion (external herniation) of the bowel can lead to venous outflow obstruction, resulting in stasis of blood, edema, and entrapment (incarceration). This can be followed by arterial and venous insufficiency (strangulation) leading to infarction.



Fibrous bands of scar tissue between bowel segments, the abdominal wall, or operative sites. The fibrous bands can lead to obstruction, as well as the formation of closed loops through which the bowel can slide through and become entrapped (internal herniation). Fibrous adhesions are usually secondary to previous surgical procedures, abdominal infection, or other causes of peritoneal injury/inflammation such as endometriosis. Rarely, fibrous adhesions can be congenital.



Complete twisting of a loop of bowel about its mesenteric base. This can lead to obstruction and vascular compromise with the potential for bowel infarction. Volvulus most often occurs in the sigmoid colon, followed by the cecum, and can involve small bowel, stomach, and transverse colon. Developmental anomalies of embryologic gut rotation (such as malrotation) can lead to volvulus in children as well as adults.


Diaphragmatic hernia

defect allows abdominal viscera to herniate into the thoracic cavity; can lead to pulmonary hypoplasia.



closure of ventral abdominal musculature is incomplete, and abdominal viscera herniate into a ventral membranous (peritoneal) sac



similar to omphalocele, but defect involves all layers of the abdominal wall.


Meckel’s diverticulum

A true diverticulum of the small bowel, composed of all three layers (mucosa, submucosa, and muscularis propria).

Occurs as a result of failed involution of the vitelline duct, which connects the developing gut to the yolk sac.

Located on the antimesenteric side of the ileum in 2% of the population, they are usually present within 2 feet of the ileocecal valve, generally 2 inches long, twice as common in males as females, and if symptomatic, symptoms occur by age two (although only 4 % of patients with a Meckel diverticulum develop symptoms).

Complications of Meckel’s diverticulum include ulceration (may have ectopic gastric mucosa with acid production and peptic ulcers in adjacent ileum), perforation, hemorrhage, fistula formation to the bladder, and intussusception. If a Meckel diverticulum is incidentally encountered at surgery for another reason, some recommend removal.


Hirschsprung’s disease

Results when the normal migration of neural crest cells from cecum to rectum is arrested prematurely or when the ganglion cells undergo premature death.

Occurs in 1 of 5000 live births, mostly males (M:F ratio 4:1). Etiologic mechanism is unknown, but appears to be genetic. Many patients have heterozygous loss-of-function mutations of the receptor tyrosine kinase RET. Some cases are familial as opposed to sporadic and some are associated with other congenital anomalies (10% of cases occur in patients with Down’s syndrome).

The most common form (75%) involves the distal sigmoid colon and rectum (classic short-segment disease). The affected segment lacks ganglion cells in both the submucosal (Meissner) and myenteric (Auerbach) plexus. Coordinated peristaltic contractions are absent, leading to functional obstruction and dilation proximally.

Patients typically present with failure to pass meconium in the neonatal period; infants and older children present with obstructive constipation, abdominal distension, and vomiting. Diagnosis is accomplished with imaging studies, rectal manometry, and biopsy to demonstrate loss of ganglion cells. Complications include enterocolitis, perforation, and peritonitis. Treatment is removal of the aganglionic segment with anastomosis.


Celiac disease

Celiac sprue is an immune mediated enteropathy triggered by the ingestion of gluten-containing grains such as wheat, barley, or rye in genetically predisposed individuals. Incidence in European or Caucasian populations is 0.5 to 1%.

Sensitivity to gluten and the alcohol soluble fraction of gluten, gliadin, results in an immune reaction which damages the surface epithelium of the small bowel (intraepithelial lymphocytes and villous atrophy, see figure, next slide).

While it is unknown why an individual would develop the disease, host genetic factors appear to be involved, since almost all individuals with celiac disease carry HLA allele HLA-DQ2 or HLA-DQ8 (but note: not all patients who are HLA-DQ2 or HLA-DQ8 have celiac disease). There is also an association of celiac disease with other autoimmune diseases such as type I diabetes, thyroiditis, sjogrens syndrome, rheumatoid arthritis, and immune mediated liver diseases (not a complete list). Incidence of selective IgA deficiency is also increased in celiac sprue.



Rare autosomal recessive disorder caused by a mutation in the microsomal triglyceride transfer protein (MTP) that catalyzes the transport of triglycerides, cholesterol esters, and phospholipids from the enterocyte. As such, monoglycerides are not assembled into chylomicrons and triglycerides accumulate within the cytoplasm, which can be seen microscopically. Abetalipoproteinemia is an example of a disorder of transepithelial transport.

Patients typically present in infancy with failure to thrive, diarrhea, and steatorrhea. Plasma apolipoprotein B (Apo B) is absent. Failure to absorb essential fatty acids leads to deficiencies of fat soluble vitamins (e.g. vitamin E deficiency). Lipid membrane defects in RBCs produces burr cells (acanthocytes) in the peripheral blood.


Whipple disease

Systemic infection caused by a gram-positive actinomycete, Tropheryma whippelii.

Organism-laden macrophages accumulate within the lamina propria of the small bowel and within mesenteric lymph nodes, leading to lymphatic obstruction. The bacteria laden-macrophages can also accumulate in synovial membranes, cardiac valves, brain, and other organs.

Clinical presentation is usually diarrhea, weight loss, malabsorption, and abdominal pain. Extraintestinal symptoms, which can occur before malabsorption becomes evident, include arthritis, arthralgia, fever, lymphadenopathy, and neurologic, cardiac (endocarditis), or pulmonary disease.


Pancreatic insufficiency

Most often due to alcoholic induced chronic pancreatitis in adults, and cystic fibrosis in children. Decreased luminal lipase and trypsin results in undigested fats and protein in the stool. Carbohydrate absorption is not affected.


Bile salt/acid deficiency

multiple causes, including:

Inadequate synthesis of bile salts/acids from cholesterol (e.g. cirrhosis).

Blockage of bile excretion: (e.g. Primary Biliary Cirrhosis, choledocolithiasis (stone in common bile duct).

Bacterial overgrowth in small bowel with destruction of bile salts/acid: (e.g. small bowel diverticula).

Terminal ileal disease, preventing recycling of bile salts/acid (e.g. Crohns disease, terminal ileum resection).



defined as inflammation of the thin, mesothelial covered layer of tissue that lines the abdominal cavity (peritoneum) and covers most of the abdominal organs (serosa). Many possible causes, including:

Bacterial peritonitis: can be secondary to perforation of a viscus (e.g. acute appendicitis, peptic ulcer, acute cholecystitis, diverticulitis, ischemic bowel, trauma), acute salpingitis, and peritoneal dialysis. Also can occur as spontaneous bacterial peritonitis (bacterial infection occurring in the setting of ascites, without obvious source of contamination).

Bile peritonitis: leakage of bile causes chemical irritation.

Acute hemorrhagic necrotizing pancreatitis.

Foreign material, either exogenous (e.g. talc or sutures, usually local reaction), or endogenous (ruptured dermoid cyst of ovary induces foreign body reaction).

Endometriosis: localized hemorrhage.



defined as the accumulation of excess fluid in the peritoneal cavity.

Many causes, but portal hypertension associated with cirrhosis is the most common cause (see list).

Mechanisms for the development of ascites include “transudative” processes such as portal hypertension, decreased osmotic pressure (e.g. hypoalbuminemia), and “exudative” processes such as peritoneal disease resulting in extravasation of exudative fluid (e.g. peritoneal malignancy). In portal hypertension with cirrhosis, the mechanisms of fluid accumulation are multifactorial, involving splanchnic vasodilation with increased sodium and water retention, hepatic sinusoidal hypertension with increased hepatic lymph fluid (this process also augmented by hypoalbuminemia), and percolation of the hepatic lymphatic fluid into the peritoneal cavity.

In obese individuals, detecting the presence of ascites by physical exam can be problematic. Imaging studies can be used, with abdominal ultrasound preferred over CT scan.

A complication of ascites can be spontaneous bacterial peritonitis, a bacterial infection developing in the absence of a known contaminating source. An exudate of acute neutrophilic inflammation and fibrin is present on the serosal and peritoneal surfaces, and the ascitic fluid exhibits increased numbers of neutrophils. Organism is detected with gram stain and culture.



are branched polymers of phenolic subunits. They are found in the stems and seeds of fruits.

Insoluble fiber decreases intestinal transit time and increases fecal bulk.



is a branched polymer abundant in bran, whole grains, and nuts. (Hemicelluloses with acidic side chains can be soluble.)

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.

Insoluble fiber decreases intestinal transit time and increases fecal bulk.



branched polymers abundant in apples, strawberries and apples. They are almost completely degraded by gut bacteria.

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.

Viscous fibers delay gastric emptying, decrease mixing of food with digestive enzymes, decrease nutrient diffusion, and increases small intestine transit time.



hydrocolloids, are secreted by plants to close wounds. They are common food additives, and are completely fermented by gut bacteria.

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.

Viscous fibers delay gastric emptying, decrease mixing of food with digestive enzymes, decrease nutrient diffusion, and increases small intestine transit time.



found in oats, barley and mushrooms. They are fermented by gut bacteria to short chain fatty acids.

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.

Viscous fibers delay gastric emptying, decrease mixing of food with digestive enzymes, decrease nutrient diffusion, and increases small intestine transit time.



a.k.a. polyfructose, are found in asparagus, leeks, onions, garlic, tomato and banana. They are prebiotics, promoting the growth of bifidobacteria (gram positive anaerobes) in the gut.

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.



a.k.a. mucilage, has a structure similar to gums. It is quite indigestible and holds a lot of water.

Soluble fiber delays gastric emptying, increases transit time through the GI, and decreases nutrient uptake.

Viscous fibers delay gastric emptying, decrease mixing of food with digestive enzymes, decrease nutrient diffusion, and increases small intestine transit time.



is a polymer of glucose and sorbitol used as a food additive to replace sugar. It is soluble, and partially fermented by the gut.



Insoluble fiber decreases intestinal transit time and increases fecal bulk.


Beneficial effects of a diet high in fiber

Decreased lipid absorption
Fiber prevents micelle formation required for fat uptake.

Lowered serum cholesterol concentrations
Increased excretion (and reduced uptake) of bile acids

Gut microbiome
Fiber promotes the growth of lactobacilli and bifidobacteria
Fiber is used by bacteria to generate short chain fatty acids

Increased fecal bulk
Decreased intraluminal pressure decreases diverticulitis


Short chain fatty acids

transported through intestinal epithelial cells directly to the blood. They are not packaged in chylomicrons.

produced by fermentation of dietary fiber affect immune cells by acting as a ligand for GPR43, and by inhibiting histone deacetylases (HDAC).

GPR43 is also expressed on adipocytes. Activation by short chain fatty acids inhibits insulin dependent storage of fatty acids, increasing their use by other tissues.


breast milk

Lactose, a disaccharide of galactose and glucose, is the main sugar in milk. It is produced by lactase synthase, a dimer of galactosyltransferase and lactalbumin.

Human breast milk contains non-digestible oligosaccharides. Human milk oligosaccharides (HMOs) are metabolized by gut bacteria, and can also enter the blood and have immunomodulatory effects

Human milk oligosaccharides can pass through the gut epithelium and are present in infants’ blood. They can act as ‘decoy receptors’, preventing attachment of pathogens to cellular glycolipids and glycoproteins.



sodium-glucose/galactose cotransporter-1
Monosaccharide uptake occurs in duodenum and jejunum

Glucose (and galactose) are actively taken up through a Na+-monosaccharide symporter, SGLT1 (2 Na+/1 sugar) This is a secondary active transport process, critically dependent upon low intracellular Na+ generated by the Na+/K+ pump



fructose transporter
Monosaccharide uptake occurs in duodenum and jejunum
Fructose uptake is promoted by a facilitated transporter



All monosaccharides leave the basolateral membrane via Glut2 and go to the liver.


Amino acid absorption

-Occurs in villi of duodenum and jejunum.
- Digestion is aided by brush border endo- and exopeptidases generating single amino acids
- Amino acids are transported across the apical membrane by Na+ dependent symporters dependent on the basolateral Na+/K+ pump (secondary active transport).
- Many of these enyzmes and transporters are degraded and resynthesized with each meal
-Peptide transporter 1 PEPT1 cotransports peptides with protons
- Apical sodium/hydrogen exchanger (NHE) supplies the luminal H+ ion and is supported by the basolateral Na+/K+ ATPase.
- Absorbed peptides are further digested by cytosolic proteases.
- Basolateral transporters export surplus amino acids into the blood.


gastric lipase

Chief cells secrete gastric lipase- not required but facilitates 10-30% of lipolysis
Gastric lipase optimal pH is 5.4 and has a prominent role in neonates due to developmental delay of pancreatic enzyme expression and in people with pancreatic insufficiency.
Free fatty acids in the duodenum trigger the release of CCK that activates pancreatic acinar secretion of lipase and procolipase.Pancreatic lipase activity is inhibited by low pH and bile acids prevent lipase binding to fat droplets.Colipase is activated by trypsin and binds bile acids recruiting lipase to cleave fatty acids.


Cholesterol esterase

broad specificity and can hydrolyze the 2-position fatty acid left untouched by lipase

Pancreas acinar cells produce additional enzymes that contribute to lipid digestion and many become active in the duodenum which contains higher levels of calcium


Phospholipase A2

Secreted Phospholipase A2 converts phospholipids (cell membranes) into fatty acids and lysophospholipids

Pancreas acinar cells produce additional enzymes that contribute to lipid digestion and many become active in the duodenum which contains higher levels of calcium


Pancreas Autodigestion

Trypsin starts it (usually a proenzyme)
Phospholipase A – affects the pulmonary system causing ARDS (adult respiratory distress syndrome)
Elactase – causes vascular damage/ hemorrhage
Lipase - induces fat necrosis
Chymoytrypsin – causes edema/ vascular injury
Parenchymal edema and peripancreatic fat necrosis occurs first. This is called acute edematous pancreatitis. When necrosis involves the parenchyma along with hemorrhage and gland dysfunction it is described as hemorrhagic or necrotizing pancreatitis.



Mid-epigastric pain (95%)
Moderately rapid onset (~30 minutes)
Progressive & constant
Can radiate to the back (50%)
Nausea / vomiting (60-80%

ETOH (by far the most common cause)


Pancreatitis Labs

Increased Amylase/ lipase
Lipase is both more sensitive and specific than amylase
Increased WBC and left shift
Increased glucose: Catecholamine release/ decreased insulin


Pancreatitis Treatment

IV hydration
NPO (nothing oral)
Pain control
Typically improves in 3-7 days



anal sphincter dyssynergia



blood in the stool



Failure of forward movement of intestinal contents.



feeling that you need to pass stool even when bowels are empty


iron absorbtion

At the brush border, a reductase reduces ferric iron to ferrous iron.
Fe2+ then is transported through the divalent metal transporter -1 (DMT1).

Within the cell, iron is stored bound to ferritin (a protein).

Iron transport in the blood requires oxidation to Fe3+ by hephaestin (HP; ceruloplasmin). This is a copper requiring enzyme.

Fe3+ then binds transferritin for transport to tissues.

Regulation of iron uptake is through hepcidin. When iron stores in the liver are high, hepcidin is produced. It binds ferroportin (FPN) and causes its degradation.

Iron interactions:
Vitamin C enhances absorption and maintains iron in the reduced state.
Copper is required for export from enterocytes.
Iron inhibits zinc absorption.



In the diet, copper is found in meat, shellfish, and nuts

A brush border reductase reduces Cu2+ to Cu+.

Cu+ then is transported through CTR1.

Cu+ can then enter the blood through ATP7A, a basolateral transporter, and circulate bound to proteins e.g. albumin.

Copper is a cofactor for superoxide dismutase, an antioxidant enzyme.

Copper deficiency:
May occur in people who consume a lot of zinc, or a lot of proton pump inhibitors.
Symptoms: anemia, leukopenia, hypopigmentation of skin & hair, altered cholesterol metabolism.

Copper toxicity:
acute: epigastric pain, nausea, vomiting, diarrhea
chronic: hematuria, liver damage, kidney damage
Wilson disease is caused by mutation in the liver specific copper transporter ATP7B.


Menkes kinky hair syndrome

caused by mutations in ATP7A. It is characterized by hypothermia, hypotonia, poor feeding, failure to thrive, and seizures.

Patients have normal hair at birth, but it becomes brittle and sparse as they age.


Wilson disease

caused by mutation in the liver specific copper transporter ATP7B.

ATP7B normally transports excess copper into the bile for excretion. When it is defective, copper accumulates and ‘leaks out’ unbound to ceruloplasmin.

Treatment is to avoid high copper foods, and chelation therapy.


Initial upper GI bleed management

Remember ABC’s

IV access
At least 2 large bore IVs

Blood products



Presentation: Dramatic bleeding, usually hematemesis
Causes: Portal hypertension
Associated with: Liver disease/cirrhosis

Octreotide or Vasopressin
Proton Pump inhibitor
Non-selective Beta-blocker
Variceal band ligation


Responsible for tolerance

Treg cells