Exam I Flashcards
Physio: These cells are in the muscularis mucosa, and secrete pepsinogen, lipase and leptin.
Secretion is activated by HCl and Ach (inc. pepsinogen)
Chief cells
*pepsinogen – cleaved; protein metabolism
Physio: These cells are located in the body of the stomach and secrete HCl and IF.
Secretion is stimulated by histamine, gastrin and Ach (PNS).
Parietal cells
Physio: These cells are located in the antrum of the stomach. They secrete gastrin which stimulate parietal cells to secrete HCl
G-cells
Physio: These cells secrete trefoil factors (protective coating for the stomach) and are located in the antrum
Mucous cells
Physio: Histamine and Somatostatin are paracrines. Where do they originate and what are their functions?
- Somatostatin
- -D cells
- -inhibit gastric acid secretion
stimulus: pH < 3 - Histamine
- -increase gastric acid secretion
Physio: CCK is a hormone that is secreted from I cells. It is stimulated by fats, peptides, and amino acids.
What are its functions?
a. Inc. gallbladder activity (bile secretion)
b. Increase pancreas activity (HCO3-)
c. Increase growth of the pancreas
d. Decrease gastric motility/secretions and emptying
All of the above
Physio: A hormone secreted by S-cells. It is stimulated by fat and acid, and functions to increase HCO3- from the pancreas.
Secretin
- nature’s antacid
- dec. gastric acid
Physio: A hormone that is stimulated by all 3 food groups (lipids, proteins, and glucose). It functions to increase insulin and decrease gastric acid
GIP
Physio: A candidate hormone from the M-cells of the upper duodenum that stimulates the migrating (myoelectric) motor complex.
Motilin
- fasting state
- erythromycin stimulates
Physio: Alpha cells of the pancreas produce
glucagon
Physio: Beta cells of the pancreas produce
Insulin
Physio: F-cells secrete _______, a candidate hormone which functions to ______
Pancreatic polypeptide
Fxn: Decrease pancreatic enzyme secretion; dec. HCO3-
Stimulus: Cho, protein, lipid ingestion
Physio: Acid secretion occurs in 3 phases:
- The cephalic phase: mediated by the ______ nerve. It is triggered by taste, sight, smell and thought of food.
- The _____ phase: food enters the stomach, causing release of gastrin and stimulation of Histamine and Hcl
- Intestinal phase: protein enters the duodenum. Overall effect reduces acid secretion. _____ is released which acts on enterochromaffin-like cells (inhibits histamine).
- vagus
- gastric
- Peptide YY
Physio: _____ factilitates HCO3- and mucous production
prostaglandin E
Physio: The exocrine pancreas secretes electrolytes and inactive ensymes (zymogens) which are activated upon entering the duodenum.
Pancreatic secretions are normally ___ with plasma
Isotonic
- HCO3- neutralize
- Enzymes involved in digestion of fat, carbs protein
Physio: Colipase is a cofactor that is secreted by the pancreas. What is its function?
Inc. efficiency of lipase
Physio: Large dietary lipids are primarily digested in the duodenum by pancreatic enzymes such as
- cholesterol esterase
- lipase
- phospholipase A2
Physio: _______ aid in lipid metabolism by emulsifying the fatty acids and monoglycerides into micelles
bile salts
*fa’s can then diffuse into enterocytes where they are packaged into chylomicrons and delivered to lymph.
Physio: Lipid absorption occurs primarily in the
jejunum
Physio: The main function of pepsin is
proteolysis
*other proteases activated by trypsin
Physio: Iron is absorbed in the duodenum as
Fe2+
*in alkaline env. = Fe3+
Physio: A candidate hormone that arises from Intestinal cells in response to fat and hypOglycemia. It increases hepatic glycogenolysis and gluconeogenesis.
Enteroglucagon
*inc. glucose production in reponse to low glucose
Physio: A candidate hormone that arises from intestinal L cells. It is secreted in response to HypERglycemia. It stimulates glucose-dependent insulin (B-cells) secretion, decreases glucagon and decreases gastric emptying
a. GLP-1
b. Pepsin
c. Enteroglucagon
d. Ghrelin
Glucagon-like peptide 1
I = inhibit
**Incretin
Physio: Which of the following decreases anorexigenic neurons, increases orexigenic neurons and promotes appetite?
a. Ghrelin
b. Peptide YY
c. GLP-1
d. Insulin
e. Leptin
Ghrelin
**Hypothalamus:
Satiety center: ventromedial nucleus of hypothalamus
Feeding center: LHA (lateral nucleus of hypothalamus)
Physio: Which of the following substances promotes appetite by inhibiting anorexigenic neurons, and stimulating orexigenic neurons?
a. Ghrelin
b. Peptide YY
c. GLP-1
d. Insulin
e. Leptin
Ghrelin
**Hypothalamus: VPN, LHA
Physio: Which of the following Neurotransmitters is responsible for smooth muscle contraction and relaxation of sphincters?
a. acetylcholine
b. NE
c. VIP
d. GRP
Ach
- inc. salivary secretion
- inc. gastric secretion
- inc. pancreatic secretion
*PNS
Physio: Norepinephrine, Neuropeptide Y and VIP all play a role in relaxing the smooth muscle of the GI tract.
- _________ constricts sphincters and increases saliva.
- _______ inc. intestinal and pancreatic secretion.
- _______ decreases intestinal secretions.
- NE
- -contract spincters
- -salivary secretion - VIP
- -inc. intestinal and pancreatic secretion - Neuropeptide Y
- -dec. intestinal secretions
Physio: Substance P is secreted with Acetylcholine. What is its role?
SM contraction
*inc. salivary secretion
Physio: Enkephalins are neutrotransmitters that play a role in _______ GI motility and decreasing intestinal secretions.
Decrease GI motility
Physio: Leptin is a substance that is secreted by fat cells in response to body fat levels. What is the function of this substance?
Decrease appetite
inc. anorexigenic, dec. orexigenic
Physio: The 3 phases of swallowing are:
- _____ phase: Tongue forces bolus back to pharynx
- _____ phase: The soft palate is pulled upward, the epiglottis covers the larynx, and the UES relaxes.
- _____ phase: The UES closes, and the primary peristaltic wave propels food. Receptive relaxation occurs here.
- ORal
- Pharyngeal
- -peristalsis propels bolus through UES - Esophageal
- -UES closes
- -primary and secondary peristatltic waves
- -Receptive relaxation (LES opens)
- -LES closes
Physio: Gastric motility is inhibited by the SNS and stimulated by the PNS. What other factors influence gastric motility?
- Liquids > CHO, > protein > fat
- Isotonic contents empty faster
- Fat and H+ SLOW emptying
Physio: In the small intestine, the peristaltic reflex acts to allow movement of the bolus down the tube. Describe the peristaltic reflex
- enterochrommafin-like cells
- -secrete 5HT - Ach, P, Y
- -contract circular muscle (CM)
- -longitudinal (LM) relaxes - VIP, NO
- -CM relaxes
- -LM contracts
Physio: A vomiting center in the medulla coordinates the vomiting reflex. Afferent info comes to the vomiting center from the vestibular system, back of the throat, Gi tract, and chemoreceptors.
The vomiting reflex involves reverse peristalsis. Explain
- Simultaneous contraction of thoracic diaphragm, ab muscles against glottis
- -relax LES and diaphragm - High intraabdominal pressure moves contents into esophagus
- Breathing muscles contract
- -inc. thoracic pressure - Expulsion of vomit from mouth
NOTE: The UES remains closed with retching; contents return to stomach
*cannabinoid receptors inhibits vomiting center
Physio: Salivary secretions are regulated by both the PNS and SNS.
- The primary NT for the sympathetic nervous system is _______ and it induces secretion of a glycoprotein rich mucous.
- The primary NT for the parasympathetic nervous system is _______ and it induces secretion of a serous, enzyme rich mucous.
- Sympathetic:
- -NE
* glycoprotein rich mucous - Parasympathetic:
- -Ach
- -inc. serous, enzyme rich
*dry mouth = dec. parasympathetic
NOTE: salivary secretions inhibited by sleep, dehydration, atropine
Physio: Bile functions to emulsify lipids facilitating digestion. It also plays a role in producing micelles that are essential for absorption.
What is the difference between primary bile acids and secondary bile acids?
Primary:
- -cholic/chenodoeoxycholic acid
- -synthesized in liver (from cholesterol)
Secondary:
- -deoxycholic/lithocholic
- -produced via intestinal bacteria
Physio: Digested products include FFA, 2-monoglyceride, cholesterol and lysophospholipid. These lipophilic products are absorbed into the cell, re-esterified, and formed into _______ that can leave the cell (exocytosed) and enter lymphatics
chylomicrons
Physio:
- Na and Cl are absorbed in the _____ GI tract
- K+ is absorbed in the _____ and secreted in the colon
- HCO3- is absorbed in the ______ and secreted in the ileum
- Vit. D must be activated in the liver and kidney. Vit. D induces synthesis of ______ protein
- Lipids are absorbed in the ____
- Iron absorbed in the
- Entire GI tract
- Small intestine
- Jejunum
- calbindin protein
- Jejunum
- Duodenum
Physio: Iron is absorbed as heme or Free iron. It binds to _______ in the cell and is transported in the blood, where it binds to transferrin.
apoferritin
*Fe2+ deficiency MC cause of anemia
NOTE: transferrin (major iron transport protein in circulation - binds Fe3+ form); Ferroportin transports Fe2+
Physio: B12 binds to proteins in ingested food. It then binds to ______ protein (haptocorrin) in the stomach, and subsequently binds IF in the SI. It is finally absorbed in the terminal ileum.
R protein (haptocorrin)
*gastrectomy/ilectom =
Physio: I cells secrete CCK and S cells secrete secretin.
- _________ is potentiated by Ach and is associated with acinar cells (IP3, Ca2+). It results in inc. glandular enzymes.
- _______is potentiated by Ach and #1. It is associated with ductal cells (inc. cAMP) and results in aqueous secretions (HCO3, Na). Stimulated by H+.
- CCK
- -I cells
- -Ach potentiates
- -Acinar cells: IP3, Ca2+
- -glands (inc. enzymes)
*Trp, Met, peptides, fa’s
- Secretin
- -S cells
- -Ach and CCK potentiate
- -Ductal cells: cAMP
* aqueous secretions (HCO3-, Na)
*H+ stimulates
Oral: Orofacial clefts (cleft lip/palate) most often occur in mothers >35 years, alcoholic mothers, and have an increased risk in siblings. What are complications of these clefts?
a. difficulty feeding
b. malocclusion
c. eustachian tube dysfunction
d. speech difficulties
all of the above
*psychosocial
Tx: surgical repair
NOTE: Cleft lip/palate - 50%; alone - 25%
Oral: In normal orofacial development, the maxillary processes grow medially, causing the medial nasal processes to be displaced toward the midline. These nasal processes then fuse at the midline. Simultaneously, the palatal shelves fuse in the midline.
What happens in the case of clef lip? cleft palate?
Cleft lip:
–failure of maxillary and medial nasal processes to fuse
Cleft palate:
–failure of palatal shelves to fuse
Oral: A 24 year old male presents to the clinic with a mass on his lateral neck. Upon examination, you note a well circumscribed cyst containing clear watery to mucoid debris. The cyst is measured to be 3cm in diameter.
Histology reveals:
1. fibrous walls lined by strat. squ. or pseudostratified epithelium; contains lymph tissue
It is most likely
Branchial cleft cyst
- lateral neck (along sternocleidomastoid)
- remnant of 2nd branchial arch
- ~2-5 cm diameter
Oral: A patient presents with a sore throat. She complains she has had a cough and runny nose for the past 2 days. Upon examination, you note erythema and edema of the pharynx with exudate. You also note conjunctivitis.
What is the most common cause for her pharyngitis?
Viral infection
- rhinovirus, adenovirus
- sore throat, runny nose, cough, erythema and edema
Oral: A patient presents with white plaques on the lateral tongue. He claims that it is painless, but he cannot scrape it off.
What do you suspect?
Hairy leukoplakia
*EBV reactivation
(immunocompromised)
*confluent, white area on lateral tongue; no pain
Oral: Herpes Simplex Virus (1 and 2) can cause oral (and genital) lesions. These viruses initially infect the contacted area, and then travel to the sensory root ganglia where they remain dormant.
True/False: Recurrence occurs when the dormant virus in the ganglia travels back down the nerve to the skin or oral mucosa.
True
- Present as group of vesicles on mucous membranes of lips (herpes labialis) and mouth
- latent: trigeminal ganglia
Oral: HSV-1 and HSV-2 infections can have extensive intra-oral mucous membrane involvement.
Cold sores (fever blisters) are a manifestation of recurrent HSV infection that often affects the corners of the mouth. They tend to be less severe, more localized, and of shorter duration than the primary episode. What are triggers for cold sores?
Triggers: Stress, pregnancy, menses, fever, UV light
Oral: A 31 year old female presents to the clinic with oral lesions. They appear vesicular that ulcerate. Lab confirms viral infection.
You suspect
Cold sores
*vesicles that ulcerate
Oral: A 15 month old presents with a low grade fever, sore throat, and a rash characterized by mildly painful, shallow yellow ulcers surrounded by red halos.
The rash is found on the mucosa of the mouth, palms, feet, and buttocks. What do you suspect?
Hand, Foot and Mouth Disease (Coxsackie)
- shallow, yellow ulcers surrounded by red halos
- labial or buccal mucosa (tongue, soft palate, uvula)
- palmar, plantar, interdigital surfaces of hands and feet; buttocks (maybe)
Oral: A 12 month old presents to the clinic with acute onset of high fever (102o) and painful vesicles on the posterior oropharynx (soft palate, tonsils, and uvula). Based on your experience, you know these papular lesions will become fluid-filled vesicles that will eventually rupture forming shallow, painless yellow-gray ulcers.
What is the child presenting with? How is it treated?
Herpangina (Coxsackie)
Tx: Spontaneous resolution
- papules – 1-2mm fluid filled vesicles – rupture to form shallow, yellow gray ulcers
- acute onset high fever (102-104F)
Oral: A patient presents with the following:
- abrupt onset sore throat
- tonsillar exudate
- cervical adenopathy
- fever
- palatal petechiae
You note her pharyngitis is bacterial. What do you suspect?
Strep pyogenes
(Group A)
Tx: Antibiotics
Oral: What are complications of group A strep?
a. acute rheumatic fever
b. peritonsillar abscess
c. cleft palate/lip
d. ludwig’s angina
A and B
- acute rheumatic fever (antibiotics during initial infection)
- peritonsillar abscess (GAS + fusobacterium necrophorum (anerobic))
Oral: A patient presents with thrombophlebitis (clotting) of the internal jugular vein. He states he had strep throat when he was younger, but did not receive treatment for it.
Labs indicate an anaerobic bacterium. What do you suspect? What is the outcome?
Lemierre’s syndrome (fusobacterium necrophorum)
Features:
- thrombophlebitis of IJV
- -rare
- -potentially fatal
Oral: A patient presents with fever, chills, malaise, drooling, mouth pain and dysphagia.
PMH significant for recent infection of his upper molar (dental).
You suspect Ludwig’s angina, an infection of the submandibular space by the flora of the oral cavity (polymicrobial; viridans). What is a major concern?
Airway obstruction
*monitor and prevent asphyxia
- -aggressive, spread rapidly
- -muffled voice or can’t speak
Oral: Cervicofacial actinomycosis involves oral colonization by Actinomyces. It is often introduced into the mucosa by mucosal breach (from infection or trauma). Infection then ensues, forming abscesses and draining sinus tracts.
What are risk factors? Who are most at risk?
RIsk factors:
- -diabetes mellitus
- -immunosuppressed
- -malnutrition
Most at risk: poor oral hygiene
Clinical: slowly progressive mass in the neck/face (mandible region) w/ purulent discharge (sulfurous granules).
Oral: A patient presents with a slow growing mandibular mass with purulent discharge containing “sulfur granules”. These granules are yellow aggregates of pus + gram (+) filamentous, anaerobic bacteria.
This best describes?
Cervicofacial actinomycosis
(“sulfur granules”) actinomyces + pus
Oral: ______ refers to the localized destruction of teeth by acid-producing plaque bacteria.
This can be prevented by flouridation of water sources.
Dental caries
*flouride incorporated into the enamel = resists degradation
Oral: True/False - Although the mechanism is unclear, excess fluoride consumption early in life can cause hypomineralization of the dental enamel.
This can lead to white to brown tooth discoloration
True
**fluoride may directly impair rate of mineral formation
Oral: Oral candidiasis is a common local infection known as “thrush”. It is caused by candida albicans (MC). What are the risk factors associated with oral candidiasis?
- wearing dentures
- antibiotics
- immune suppression
- cellular immune deficiency (AIDS)
- inhaled corticosteroids
Oral: A patient presents with white, curd-like discharge on their tongue (red background). The discharge can be scraped off, leaving a red, raw surface.
Associated symptoms include dysphagia and mouth soreness. What do you suspect?
Thrush (oral candidiasis)
- scrape off = bleeding
- budding yeast and pseudohyphae
Oral: _______ refers to one or more small (mm) painful ulcers that are usually on the inner lip or tongue. They are typically seen in kids and adolescents.
*localized, shallow, round - oval ulcers with a gray base.
Recurrent aphthous stomatitis (“Canker sores”)
- recurrences less frequent in childhood
- spontaneous resolution 1-2 wks
Oral: The cause for recurrent apthous stomatitis (canker sores) is unknown, however, it is believed to be dysregulation in local cell-mediated immunity.
What are common associations with the development of canker sores? How are they treated?
Associations:
- stress
- trauma
- hormones
- familial
Tx:
- -symptoms (topical corticosteroid/analgesic)
- -avoid salty or acidic foods/juices
Oral: Peutz Jeghers syndrome is an autosomal dominant disorder that is characterized by multiple hmartomatous (different tissues) polyps in the GI tract. It is also associated with mucocutaneous pigmentation (hyperpigmented macules) in the mouth, lips and genitalia and poses increased risk of cancers (GI and non-GI).
It is due to a mutation in what gene?
tumor suppressor STK-11
- hamartomatous polyps
- mucocutaneous pigmentation
- cancers (breast, ovarian, other GI cancers)
- Intussusception (telescoping of bowel; currant jelly stools)
Oral: Gray-blue lines that form along the junction of the teeth and gums due to lead poisoning
Lead lines
Oral: A patient presents with a history of adrenocortical insufficiency. This insufficiency leads to increased production of pro-opiomelanocortin (a prohormone that is cleaved into ACTH, MSH and others).
Elevated levels of MSH stimulate melanin synthesis, leading to hyper-pigmentation. What do you suspect?
Addison’s disease
Oral: A patient presents with an enlarged tongue, drooling, and difficulty eating. You note he has difficulty with his speech, and has stridor due to airway obstruction. You suspect
Macroglossia
-drool, speech impairment, airway obstruction
Oral: What are common associations with macroglossia?
a. congenital hypothyroidism
b. amyloidosis
c. acromegaly
d. Addison’s disease
A-C
Tx: based on severity (speech therapy; surgical reduction)
Physio: What are the features of salivary secretions (compared to plasma)
–alkaline, high K+, hypotonic
Contain: alpha amylase, lingual lipase, mucous, glycoproteins, Igs
Physio: Salivary secretions are stimulated by? Inhibited by?
Stimulated: PNS and SNS
Inhibited by: SLeep, dehydration, atropine
Physio: Gastric secretions are viscous fluids composed of mucin and HCO3-. What molecules control acid secretion?
Ach, histamine gastrin
Somatostatin = inhibitory
Physio: The stomach is composed of Oxyntic glands and pyloric glands. The oxyntic glands have what cells?
Parietal: HCL, IF
Chief: pepsinogen
Physio: Venous blood that moves away from the stomach towards the pancreas is known as the
alkaline tide
Physio: The pancreas secretes high volumes of bicarb and enzymes, creating an isotonic solution.
What stimulates pancreatic secretions?
- Secretin – inc. HCO3-
- CCK – stimulates enzymes
- Ach – vago-vagal
NOTE: Acinar cells - CL-; Ductal cells - HCO3-
“secret ducts” = secretin/ductal cells
Physio: Crypt cells of the Small Intestine are responsible for secreting Chloride via NKCC in the basolateral membrane. Na entry drives the K+ and Cl- entry. Cl- is then secreted by CFTR into the lumen.
True/False - Luminal Cl- pulls Na and H2O, creating isotonic secretions
True
**cAMP opens Chloride channel (via G alpha protein)
Imaging: Achalasia is a disorder characterized by failure of the LES to relax during swallowing. It often presents with dysphagia (hard to swallow) for solids and liquids, regurgitation of food, retrosternal chest pain, and weight loss.
What is a characteristic finding on imagin?
“bird’s beak” sign
- proximal esophageal dilation; narrowing at gastro-esophageal junction
- degeneration of inhibitory neurons
NOTE: Chagas can cause secondary achalasia
Imaging:
- The fundus of the stomach is supplied by ____
- The lesser curvature is supplied by _____
- The greater curvature is supplied by
- This region of the SI has the thickest plicae circulares
- short gastric arteries
- left and right gastric
- L and R gastro-omental
- jejunum
Imaging: There are 4 anatomical parts of the duodenum:
- Superior
- Descending
- Inferior
- Ascending
What are their features?
- Superior
- -L1
- -mobile, intraperitoneal - Descending
- -L1-L3
- -pancreatic and common bile empty here (Vater) - Inferior
- -horizontal
- -L3 - Ascending
- -L2 (superiorly)
- -terminates at duodenal-jejnual flexure
Imaging: What happens when there is a mass in the pancreatic head (closeley associated with the duodenum)?
Jaundice
–due to obstruction of distal pancreatic and distal common bile ducts. No bile will enter the duodenum
Imaging: Repeated injuty to the pancreas (e.g. alcohol abuse) can cause chronic pancreatitis. This results in destruction of the exocrine cells, and thus, loss of pancreatic enzymes. What is the significance of this?
- malabsorption (enzymes aren’t available to digest fat)
clinical: steatorrhea (greasy stool), secondary diabetes
Imaging: A small bowel obstruction can be indicated by the presence of
- plicae circularis on imaging
- SI more centrally located
* *dilated, air filled loops of bowel arranged in a step-wise fashion
*large bowel: haustra do not span the entire bowel; peripherally located
Imaging: You receive imaging of a patient.
Imaging reveals circumferential tumor growth with focal constriction and dilation of the colon proximal to the constriction. “Apple core” sign is present.
What does this indicate?
- colorectal cancer
- circumferential tumor growth = focal constriction and dilation of the colon proximal to the constriction
NOTE: must be done with barium
Imaging: Diverticulosis is caused by small outpouchings (diverticula) of the colonic wall due to increased intraluminal pressure.
Although usually asymptomatic, what are 2 major complications associated with diverticulosis?
- Diverticulitis
- -infection/inflammation
- -pain L lower quadrant, fever, nausea, vomiting, diarrhea or constipation - Bleeding
- -MC cause of massive lower GI bleeding
Imaging: A patient presents with periumbilical pain. You perform several tests, and note rebound tenderness.
Clinical examination reveals pain over McBurney’s point (2/3 b/t umbilicus and ASIS) and a positive Rovsing’s sign (pain in right iliac fossa during palpation of left). You suspect appendicitis. What imaging would you perform? What do you look for?
Imaging: MRI, CT, US
Features: dilated tubular structure, thickened wall, fat standing
Imaging: The thoracic aorta exits the aortic hiatus at T12 to become the abdominal aorta. The abdominal aorta gives off multiple branches including
- celiac (T12)
- superior mesenteric (L1)
- inferior mesenteric (L3)
- renal artery
- common iliac arteries (L4)
Imaging: List the 5 major veins that contribute to the IVC
- Common iliac (L5)
- Lumbar (L1-L5)
- Right gonadal (L2)
- Renal (L1)
- Hepatic (T8)
Imaging: It is common to do a full CT exam on patients who experience trauma. What is the first thing that should be assessed?
Integrity of the aorta
Imaging: The branches of the celiac artery (T12) include:
- Left gastric
- Common hepatic
- Splenic
What do they supply?
- Left gastric: stomach, esophagus
- Common hepatic: liver, stomach, duodenum
- Splenic: spleen, pancreas, short gastric arteries
Imaging: The branches of the Superior Mesenteric Artery include:
- Inferior pancreaticoduodenal artery
- Intestinal arteries
- Ileocolic arteries
- Right colic artery
- Middle colic artery
What do they supply?
- Inferior pancreaticoduodenal: head of pancreas, duodenum
- Intestinal arteries: Ileum, jejunum
- Ileocolic: terminal ileum, cecum, appendix
- Right colic: ascending colon
- Middle colic: transverse colon
Imaging: The branches of the Inferior Mesenteric artery include:
- Left colic
- Sigmoid
- Superior rectal
What do they supply?
- Left colic: descending colon
- Sigmoid: sigmoid colon
- Superior rectal: terminal branch of IMA
Imaging: The GI tract is embryologically divided into
- foregut
- midgut
- hindgut
What is the blood supply/boundaries of these divisions?
- FOregut
- -celiac
- -lower esophagus to major duodenal papilla - Midgut
- -SMA
- -duodenal papilla – 2/3 transverse colon - Hindgut
- -IMA
- -2/3 transverse to upper anal canal
Imaging: The spleen is deep to ribs 9, 10 and 11.
True/False - the spleen has a very thin capsule. This is prone to rupture due to trauma such as a rib fracture
True
*splenic artery supplies spleen - rapid blood loss into peritoneal cavity
Imaging: A patient presents with LUQ pain and tenderness. You note bruising on ribs 9 and 10, confusion and dizziness. The patient is hypotensive due to extensive blood loss. What do you suspect?
Splenic rupture
Imaging: A patient presents complaining of shoulder pain and pleuritic chest pain. You notice she is breathing deeply. She states that she eats less than normal because she always feels full. On palpation, you note the spleen can be felt. What do you suspect?
Splenomegaly
- fullness, referred shoulder pain, difficulty breathing
- Risk factors: Mono (EBV), Hematological malignancy, portal HTN, malaria
Imaging: True/False - A spleen is not palpable until it is 3x its normal size
False
2x its normal size
Imaging: The tail of the pancreas lies in close proximity to the splenic hilum and is supplied by branches of the splenic artery.
True/False - the pancreatic tail is prone to iatrogenic injury during splenectomy when the hilum and vessels are clamped
true
Imaging: The gallbladder stores and concentrates bile before it is released into the SI. When components of bile become concentrated beyond the point of solubility, the precipitate to form gallstones.
What are the types of gallstones? which is most common?
- Cholesterol (80%)
- Bilirubin (chronic hemolysis)
- Pigment (bilirubin stones via oxidation)
Imaging: Blood flow from the spleen and GI tract is delivered to the liver through the portal vein (superior mesenteric + splenic veins).
What are the consequences of portal HTN?
- ascites (fluid in peritoneal cavity)
- Splenomegaly (lead to thrombocytopenia)
- Esophageal varices (dilated veins – hematamesis)
- Caput medusae (dilated peri-umbilical collateral veins)
Imaging: True/False - repeated injury to the liver (alcohol, chornic viral hepatitis) can cause irreversible damage (cirrhosis)
true
Oral: Inflammatory disorder of the tongue that leads to atrophy of the filiform papilla. The tongue will appear smooth, glossy and erythematous. MC due to nutritional deficits (Fe, B12, folate).
Atrophic glossitis
due to: nutritional deficiencies (Fe, B12, folate); Sjogren; oral candidiasis, protein-calories malnutrition elderly
Oral: A patient presents complaining of burning sensation in her mouth along with increased sensitivity when she eats acidic and/or salty foods. You note that her tongue appears smooth, glossy and erythematous. You suspect? How would you treat?
atrophic glossitis
Tx: correct underlying condition
Oral: Drug induced-gingival overgrowth is believed to be due to a direct effect of a drug combined with inflammatory changes induced by bacteria. With which drugs is it most often associated?
a. phenytoin
b. Isoniazid
c. cyclosporine
d. Ca2+ channel blockers
Answer: Phenytoin (anti-epileptic), Cyclosporine, Ca2+ blockers
- severity/distribution: dose and case specific
- may interfere with hygiene and impair chewing
Oral: A clinical term used to describe an asymptomatic “white plaque” that CANNOT be scraped off. It has low risk of dysplasia/malignancy.
Leukoplakia
Dx: must biopsy
Note: multifactorial (tobacco MC);
–inner lip, floor of mouth
Oral: A clinical term for “red plaque”. It is more likely to represent a dysplastic or malignant process.
Risk factors include: Tobacco (MCC), OH, and HPV.
Erythroplakia
- -red color due to subepithelial vascular dilation
- *Tobacco
Dx: Must biopsy to rule out squamous dysplasia/cancer
Oral: _______ is a benign tumor located in the mandible. It arises from teeth-forming (odontogenic) epithelium.
Imaging reveals radiolucency of the bone (“soap bubble”).
a. pyogenic granuloma
b. ameloblastoma
c. squamous cell carcinoma of the mouth
d. papillary adenoma
Ameloblastoma
- arises from teeth-forming (odontogenic) epithelium
- locally invasive; does NOT metastasize
Oral: Squamous cell carcinoma is the MC malignancy of the oral cavity. Risk factors include:
- tobacco
- alcohol
- HPV (16)
- sunlight (lower lip)
What are the MC sites?
- lower lip (vermillion border)
- floor of mouth
- lateral tongue
Oral: A 9 year old presents to the clinic with a benign tumor of the oral cavity.
On PE you note the tumor is present on the gingiva.
Histology reveals:
1. lobules of capillary-sized vessels (lobular capillary hemangioma)
You suspect
a. choriocarcinoma
b. nevus simplex
c. pyogenic granuloma
d. hemangioma
Pyogenic granuloma (benign prolif. of small vessels)
- MC kids and young adults
- MC gingiva, maybe lips, buccal mucosa, tongue
Oral: Kaposi sarcoma is a malignant neoplasm of endothelial cells. It is most often associated with HHV-8. It involves the mucous membranes, skin and viscera of the GI tract.
What are the 4 epidemiologic forms?
- AIDS associated
- -AIDS defining
- -MC AIDS malignancy - Transplant - associated
- -T-cell immunosuppression (solid organ) - Classic (sporadic)
- -elderly males; Mediterranean descent - Endemic African
- -HIV seronegative
Oral: __________ is caused by autoimmune destruction of the exocrine glands (including lacrimal and salivary glands). It is most often seen in middle aged females.
Sjogren syndrome
-lymphocytic inflammation/destruction of exocrine glands that results in fibrosis
Oral: A 45 year old female presents with complaints of dry eyes and dry mouth. She reports gritty, sand-like feeling in her eyes. Patient admits to difficulty swallowing dry foods such as crackers.
On PE you note enlargement of the salivary glands (sialadenitis).
Labs reveal:
- Anti-SSA (+)
- Anti-SSB (+)
You suspect
Sjogren syndrome
- Dry eyes
–keratoconjunctivitis sicca, xeropthalmia
(gritty feeling/sand in eyes) - Dry mouth
- -xerostomia (difficulty swallowing dry food; crackers) - Salivary gland enlargement
- -sialadenitis (inflammation)
Oral: Sjogren syndrome is caused by autoimmune destruction fo the exocrine glands (including lacrimal and salivary glands). It is most often seen in middle aged females.
Describe associated complications. How is it diagnosed?
Complications:
–inc. risk dental caries, lymphoma
Dx: Anti-Ro (SSA) and anti-La (SSB-autoabs)
Oral: A patient presents with complaints of oral pain and swelling.
On PE you note the presence of a stone in the salivary duct (Wharton’s duct - MC). Skin tenting present.
You suspect
Sialolithiasis
MC - Wharton’s duct (drains submandibular gland)
RIsk factors:
-dehydration (e.g. Sjogren), meds that dec. salivary production (anti-cholinergics)
Oral: Sialadenitis is characterized by inflammation of the salivary glands. Associated symptoms are firmness, pain and swelling.
It most often involves either the parotid or submandibular gland. What are common causes?
- Sjogren’s
- Mumps (bilateral)
- Duct obstruction (unilateral)
- -Staph aureus
- -dehydration
Oral: A pseudocyst of the minor salivary gland. It is formed when the salivary gland duct is blocked or ruptured (secondary to trauma – biting lip or cheek).
Mucocele
- secretions will dissect into the soft tissues (around the gland)
- pooling of mucous
Oral: A patient presents with painless swelling of the lower lip/buccal mucosa. You note a translucent/bluish “cyst” < 1cm on her inner lip.
What do you suspect? How do you treat?
Mucocele
- painless swelling
- translucent or bluish
Tx: resolves spontaneously or excise
Oral: Salivary gland neoplasms that occur in the parotid gland (MC) are rare and mostly benign. They will often present as a painless mass.
What features could indicate malignancy?
- tumors in the other salivary glands
- **neurologic signs (facial nerve paralysis) **
- radiation exposure (inc. risk)
Oral: Parotid tumors drain into ____ lymph nodes first, then to the upper cervical nodes
intra-parotid lymph nodes
Oral: A patient presents with a painless, slow growing, mobile mass at jaw angle
Biopsy reveals a “benign mixed tumor” that exhibits epithelial and mesenchymal differentiation.
pleomorphic adenoma
RF’S:
- MC females
- Radiation exposure (15-20 yrs. later)
- Recurrence (if incompletely excised)
- low risk of malignant transformation
- MC parotid gland
Oral: A patient presents to the clinic with a mass on his face along the parotid gland. He states that it is painless, but it seems to be growing larger.
- Social history: Smoker for 20 years
- Histology: double layer of palisading neoplastic columnar and cuboidal epithelial cells resting on a dense lymphoiod stroma (w/ germinal centers)
What do you suspect?
Warthin tumor
- MC males
- MC smoking
- Parotid ONLY
- no malignant change
Oral: ________ is the MC primary malignant tumor of salivary glands. It is composed of an admixture of 3 cell types:
- mucocytes
- epidermoid cells
- intermediate cells
It most often occurs in the parotid gland and can be low, intermediate or high grade depending on the degree of anaplasia.
Mucoepidermoid carcinoma
Clinical course and prognosis depend on the grade.
Oral: Adenoid cystic carcinoma is a relatively uncommon and slow growing salivary gland tumor. It is aggressive and has a propensity for ____ invasion.
Typically, prognosis is poor (risk of distant metastasis years later).
perineural
PUD drugs: _________ primarily act to neutralize acid secreted in the stomach. They provide subsequent mucosa protection
Antacids
PUD drugs: _____ protect any area of the GI system from further damage and/or promote recovery
Mucosa protectants
PUD drugs: _____ block/reduce gastric acid secretion
H2 antagonists and protein pump inhibitors
*H2 antags = first line Tx for peptic ulcers
PUD drugs: Treat H. pylori
Antibiotics
PUD: Antacids act to:
- Neutralize the acid secreted in the stomach.
- -formulations include Na, Ca, Al or Mg ions. - Decrease tissue injury by maintaining the pH at ~5 (reducing pepsin activity).
- Decrease acidity and aid with headache
- -buffered antacid (alka-seltzer) - aspirin + NaHCO3 + citric acid
What do antacids NOT do?
- do not prevent acid production
- do not coat the lining of peptic ulcers or GI mucosa
PUD: What are the adverse effects of the following antacids?
- NAHCO3 (high neutralizing capacity)
- CaCO3 (moderate)
- Al(OH3) (high)
- Mg(OH2) (high)
- NaHCO3
- -short, fast effects
- -systemic alkalosis - CaCO3
- -moderate
- -hypercalcemia; inc. gastrin; acid rebound - AlOH3
- -Constipation - Mg
- -diarrhea
- –hyperMg (renal insufficiency)
PUD: Which of the following is a drug interaction of Antacids?
a. decrease absorption of acidic drugs (e.g. phenytoin)
b. form insolbule chelate complexes w/ antibiotics
c. decrease cimetidine bioavailability
All of the above
- decrease absorption of acidic drugs
- –digoxin, phenytoin, chlorpromazine) = decrease their efficacy. - chelate complexes
- -tetracyclines and fluouroquinolones
- -take 4 hours before (or 2 hrs. after antibiotic) - decrease cimetidine bioavailability
- -take drugs apart
PUD: What is a contraindication for antacids?
renal failure (hypermagnasemia, AI toxicity)
PUD: Mucosal protectants are used to treat stomach, duodenal, and esophageal ulcers (less efficiently than H2 antagonists and PPI’s).
Examples of these drugs include:
- Bismuth salicylate
- Sucralfate
- Misoprostol
_____relieves heartburn, nausea and diarrhea. It limits acid secretion in the GIT, and inhibits H. pylori.
Bismuth
*anti-inflammatory effect (salicylic acid)
NOTE:
-poorly absorbed
Adverse: black stools
Cx: bleeding with ulcers
PUD: Mucosal protectants are used to treat stomach, duodenal, and esophageal ulcers (less efficiently than H2 antagonists and PPI’s).
Examples of these drugs include:
- Bismuth salicylate
- Sucralfate
- Misoprostol
_____ prevents ulcers produced by NSAIDS.
Sucralfate
NOTE:
- -local effect
- -Adverse: Constipation, dry mouth
- -Cx: hypophasphatemia; renal dysfxn
PUD: Which of the following are mechanisms of action of sucralfate?
a. interacts with proteins at the ulcer site to form a protective layer
b. prevents acid exposure and promotes faster healing
c. inhibits pepsin = dec. tissue injury
d. binds bile salts to protect the stomach lining (from bile acid)
All of the above
Also:
-Inc. PG secretion: restitution and preservation of gastric mucosa
-Suppress H. pylor infection
PUD: Mucosal protectants are used to treat stomach, duodenal, and esophageal ulcers (less efficiently than H2 antagonists and PPI’s).
Examples of these drugs include:
- Bismuth salicylate
- Sucralfate
- Misoprostol
____ is a PGE1 analog that is used (rarely) for the prevention and treatment of ulcers produced by NSAIDS. It acts to protect the mucosa by increasing HCO3- and mucous secretion.
Misoprostol
Adverse: Diarrhea
Cx: Pregnancy (miscarriages; birth defects)
PUD: List the drug interactions of mucosa protectants
- Bismuth salicylate
- Mg antacids and misoprostol
- Sucralfate
- Bismuth
- -dec. absorption of tetracyclines - Mg antacids and misoprostol
- -inc. diarrhea (Mg) - Sucralfate
a. decreases efficacy of azole anti-fungals, cimetidine, digoxin
b. if px takes Lansoprazole, administer 30 min apart (it inhibits sucralfate absorption)
PUD: H2 antgonists act to inhibit gastric acid secretion and stimulate mucous synthesis/secretion. They are more often used when other treatments fail.
What is their mechanism of action?
–inhibit H2 receptors (dec. HCl production)
- inhibit both meal and basal acid secretions
- Clinical use: Zollinger, GERD, H. pylori
PUD: H2 antagonists include Cimetidine, Famotidine and Nizatidine. Of the 3, Famotidine has the longest duration and is the most potent.
What are side effects of these drugs?
- Common
- -diarrhea, headache, constipation, nausea - Long term (high dose)
a. cimetidine: inhbits DHT = gynecomastia (men); galactorrhea (women)
PUD: List the drug interactions associated with H2 antagonists
- Prevent PPI activity
- -take 4 hrs apart - Dec. absorption of azoles, iron, cyclosporine
- Cimitedine inhibits CYP450 (dec. drug metabolism; inc. side effects)
- -warfarin, tricyclic anti-depressants, anti-convulsants
PUD: Proton Pump Inhibitors (PPI’s) are most effective for the treatment of GERD. Their efficacy is similar to H2 antagaonists (for PUD).
They can be used to treat Zollinger-Ellison at higher doses, and can be used in combo with clarithromycin for H. pylor infections. What is the MOA of PPI’s?
- prodrug – reactive agent (in parietal cell lumen)
- -covalently attach to the H+/K+ ATPase
PUD: Omeprazole (Prilosec) and Esomeprazole are types of PPI’s. Omeprazole is the racemic mix (inactive R+ isomer) that gets converted in the liver to esomeprazole (enantiomer) by CYP2C19.
It has lower efficacy in “poor metabolizers”. How does this differ from Esomeprazole (Nexium)?
Esomeprazole = same conc. for normal and poor metabolizers
PUD: To be effective, PPI’s should be taken 30 minutes before eating. Which PPI has the highest, fastest activity? Which has the highest bioavailability?
- Fastest activity
- -Rabeprazole
* 5 minutes to inhibit - Greatest bioavailability
- -Lansoprazole
PUD: PPI’s are normally well tolerated, however, the longer the exposure, the greater the risk of adverse effects.
Which of the following is a common adverse effect of PPI’s?
a. Headache, diarrhea, abdominal pain, nausea and vomiting
b. Inc. gastrin secretion – mucosal hyperplasia
c. Increased risk of bone fractures (dec. Mg)
All of the above
PUD: True/False - PPI’s have pH dependent drug interactions. The decreased acidity in the stomach (long term) can cause decreased absorption of ketoconazole, aspirin, and atazanivir. Furthermore, they can cause decreased absorption of ions including Ca2+, Magnesium and Vit. B12.
True
PUD: PPI’s can have pH- independent interactions. For example, Omeprazole/esomeprazole inhibit the metabolism (2C19, 2D6, and 3A4) of warfarin, diazepam and phenytoin, increasing drug activity and side effects.
What effects do they have with anti-platelet drugs?
Dec. anti-platelet activity of clopidogrel
PUD: True/False - PPI’s Pantoprazole/Rabeprazole have less inhibitory effects on CYP enzymes, and thus have no significant drug interactions.
True
PUD: 80-95% of patients with ulcers have an H. pylor infection. Typically treatment involves a multi-drug therapy:
- Begin Tx with acid reducing agent (H2 or PPI for 6wks)
- Next Tx with 2 or ore antibiotics or bismuth (2wks)
12-month remission rates are higher after successful eradication. What are combined drugs used to Tx H. pylori?
- Lansoprazole (omeprazole) + amoxicillin and clarithromycin
- Omeprazole + amoxicillin + rifabutin
- -if H. pylori is resistant to clarythromycin and metronidazole
- -higher eradication
PUD: For the following antibiotics, list the side effects, drug interactions and contraindications
- Clarithromycin
- Amoxicillin
- Metronidazole
- Tetracycline
- Omeprazole + Amox + Rifambu
See table in Notes
Esophageal: A mother presents to the clinic with her 3 week old infant. She reports he has been drooling, choking and spitting up after feeding.
On PE you note polyhydramnios.
Catheter placement fails (cannot pass further than ~10-15cm).
A-P CXR reveals catheter curls in the upper esophageal pouch.
You suspect
Tracheoesophageal fistula
- MC congenital abrnomality of the esophagus
- abnormal connection b/t trachea and esophagus
NOTE: associated with VACTERL: vertebral anomaly, anal atresia, CV defects, TE fistula, renal issues, limb issues
NOTE 2: MC fistula b/t distal trachea and esophagus
Esophageal: A ring of mucosal prominence in the upper esophagus. It is Idiopathic and often asymptomatic.
Clinical include dysphagia for solid food.
Esphageal web
MC - women > 40
NOTE: Seen in Plummer Vinson syndrome (web, Fe anemia, beefy red tongue)
Esophageal: How does esophageal web differ from Schatzki’s ring?
Schatzki’s is in the lower esophagus
*circumferential and symptomatic
Esophageal: Refers to herniation of abdominal tissues through the esophageal hiatus of the diaphragm. It is usually asymptomatic, but can increase the risk of reflux (GERD).
Hiatal hernia
- unknown etiology - inc. abdominal pressure (pregnancy, obesity, ascites)
- usually acquired
NOTE: may present with epigastric pain, early satiety, GERD/retching
Esophageal: With regard to hiatal hernias, most are asymptomatic. However, larger ones can increase the risk of GERD.
True/False: Surgical repair is usually reserved for symptomatic patients and for management of complications (obstruction, strangulation, perforation)
True
- NOTE: sliding hiatal hernia (defect in diaphragm - stomach slides up into chest)
- NOTE 2: parasophageal hiatal hernia (proximal stomach – adjacent to esophagus = strangulation)
Esophageal: The esophagus functions as a pump, the LES as a valve and the stomach as a reservoir.
Gastroesophageal reflux may occur as a result of:
a. absent esophageal peristalsis (e.g. achalasia, scleroderma)
b. dysfunctional LES
c. delayed gastric emptying
All of the above
a. absent esophageal peristalsis
- –achalasia, scleroderma (dec. clearance of acidic material)
b. dysfunctional LES
- -hiatal hernia, anti-cholinergic, fatty food, nicotine (reflux of gastric contents)
c. delayed gastric emptying
- -gastroparesis (inc. gastric volume and pressure overwhelms LES –GERD)
Esophageal: Gastroesophageal reflux disease can be due to decreased LES pressure, and increased intra-abdominal pressure. This leads to backflow of gastric contents (acid and bile) into the lower esophagus.
What are common etiologies leading to decreased LES pressure?
- progesterone (pregnancy)
- coffee
- alcohol
- smoking (nicotine)
- chocolate
- fatty foods
- medications (Ca2+ channel blockers, anti-Achs)
NOTE: stomach contents flow back into the esophagus causing irritation of the mucosa. Due to innappropriate, transient relaxation of the LES.
Esophageal: Gastroesophageal reflux disease can be due to decreased LES pressure, and increased intra-abdominal pressure. This leads to backflow of gastric contents (acid and bile) into the lower esophagus.
What are common etiologies leading to intra-abdominal pressure?
- coughing
- straining (valsalva)
- bending
Esophageal: A 32 year old female presents complaining of heartburn (retrosternal burning sensation), chest pain and regurgitation.
What do you suspect?
GERD
Esophageal: Complications of GERD include
- Reflux esophagitis
- bleeding
- stricture
- Barrett esophagus – CA
______ occurs when refluxed gastric acid and pepsin cause necrosiss of the esophageal mucosa that presents with erosions/ulcers
Reflux esophagitis
Esophageal: Treatment for gastroesophageal reflux disease includes:
- lifestyle changes
- medications
- surgical
List examples of lifestyle changes
- elevate head with blocks
- reduce meal size
- don’t eat immediately before bedtime
- weight loss (if overweight)
- if smoker: quit smoking
- avoid aggravating food, drinks, meds
Esophageal: Treatment for gastroesophageal reflux disease includes:
- lifestyle changes
- medications
- surgical
List examples of Medications and Surgical
Meds:
–H2 antagonists, antacids, PPI’s (omeprazole)
Surgical:
–Nissen fundoplication
(proximal stomach wrapped around distal esophagus to create anti-reflux barrier
Esophageal: Barrett’s esophagus results from chronic irritation of the distal esophagus that leads to intestinal metaplasia.
Describe this histological change
- Squamous epithelium to columnar w/ goblet cells
- Salmon colored mucosa
- predominantly white males
- inc. risk dysplasia/malignancy
Esophageal: A 38 year old HIV (+) male presents with complaints of odynophagia (pain with swallowing), dsyphagia, and chest pain. He has a CD 4 < 100 .
You suspect
Infectious esophagitis
*immunocomp, transplant px
NOTE: odynophagia - uncommon in reflux
Esophageal: A patient presents to the clinic with odynophagia (pain swallowing) and dysphagia (difficulty swallowing). You note white plaques with friability that bleed when scraped.
Labs indicate a budding yeast with pseudohyphae. What do you suspect? In what patients is this MC?
Candida esophagitis
- -odyno and dysphagia
- -friable white plaques
Patients: AIDS (AiDS defining), chemo/radiation, transplant, esophageal stasis (achalasia, strictures, scleroderma)
Esophageal: HSV 1 and 2 can cause HSV esophagitis. It typically presents in patients who are immunocompromised.
Signs and Symptoms include vesicles on their lips, odynophagia and dysphagia.
Describe their clinical appearance
Multiple, discreet “punched out” ulcers
*viral cytopathic effect: nuclear inclusions
Esophageal: CMV esophagitis presents with “serpiginous ulcers” in otherwise normal mucosa.
It most often occurs in what patients?
- immunocompromised
- organ transplant on immunosuppressive therapy
*viral cytopathic effect = nuclear and cytoplasmic inclusions
Esophageal: Increased intra-epithelial eosinophils in the absence of other known causes + dysphagia and food impaction describes
eosinophilic esophagitis
- young, white males
- Hx: food allergy, asthma, eczema, allergic rhinitis
Esophageal: What are characteristic histologic and clinical features of eosinophilic esophagitis?
- concentric mucosal rings (endoscopy)
2. innumerable eosinophils (biopsy)
Esophageal: Pill esophagitis refers to the development of erosions and or ulcers at the site where medication lodges (in esophageal lumen). Symptoms include chest pain and odynophagia. It may heal with scarring causing stricture.
What are pre-disposing factors?
Features:
–discrete ulcer with normal appearaing background mucosa
Pre-disposing:
- -inadequate liquid intake w/ pill (dry swallow)
- -recumbent position soon after ingestion
Esophageal: What are the MC medications associated with pill esophagitis?
a. NSAIDs, Bisphosphonates, Tetracyclines, Supplements
b. Anticholinergics, Bisphosphonates, Fluoroquinolones, Tetracyclines
c. ACE inhibitors, tetracyclines, NSAIDs, B-blockers
A
NSAIDs (ASA)
Bisphosphonates
Tetracylines
K+ and Fe2+ supplements
Esophageal: Achalasia is an uncommon disorder with unknown etiology. Evidence suggests an autoimmune response triggered by HSV-1.
It occurs equally in males and females between the ages of 25-60. Regardless of the underlying cause, there tends to be a lack of what within the esophagus?
lack inhibitory ganglion cells within the esophagus
Esophageal: A patient presents with difficulty swallowing (dysphagia) both liquids and solid foods.
You perform a barium swallow and esophageal manometry. Results reveal a dilated esophagus with air fluid level. “Bird beak” sign is noted.
You are concerned of his risk of aspiration because you suspect
Achalasia
- lack of esophageal peristalsis
- failure of the LES to relax during swallowing.
Esophageal: Chagas disease is an acquired cause of achalasia. It is due to infection by Trypanosoma cruzi. Although infection is lifelong, only a small minority develop serious problems.
What is the pathogenesis of Chagas?
–chronic low levels of parasites in tissues = chronic inflammation = pathologic changes
Esophageal: Chronic infection by T. cruzi is most likely to cause myocarditis. It may also involve the esophagus and colon, causing a loss of ganglion cells (leading to dilation).
What are the clinical manifestations?
–similar to achalasia (dysphagia initially to solids, eventually liquids)
-Romana’s sign: unilateral swelling of eyelid
(inflammation at inoculation site)
*megaesophagus, megacolon
Esophageal: Esophageal strictures are most often caused by
- Reflux esophagitis (MC)
- corrosive esophagitis - alkali or acid
- Iatrogenic, Pill esophagitis, Radiation esophagitis, Malignancy
Esophageal: Esophageal strictures most commonly present with dysphagia (solids). This may be progressive, but is not intermittent.
How is it treated? What are potential complications?
Tx:
-esophageal dilatation (may have to be repeated)
Complications:
- -chronic relapsing course
- -inc. risk of food impaction, aspiration
- -inc. risk of perforation
- -dilatation may need to be repeated
Esophageal: A diverticulum describes outpouching of the wall of a tubular organ.
- _______: indicates presence at birth
- ______: indicates development later in life
- ______: incolves all layers of the wall
- ______: herniation of mucosa and submucosa (through a defect in the muscular wall)
- Congenital diverticula
- Acquired diverticula
- True diverticula
- False diverticula
Esophageal: A diverticulum describes outpouching of the wall of a tubular organ.
- _____: high intra-luminal pressure pushing out against an area of weakness
- _____: pulling forces (e.g. traction) on the outside of the esophagus from an adjacent inflammatory process
- Pulsion diverticula
2. Traction diverticula
Esophageal:________ describes an uncommon, false diverticulum that arises immediately above the upper esophageal sphincter.
It is an acquired defect due to stenosis of the cricopharyngus muscle (UES) that leads to obstruction and increased intra-luminal pressure proximally.
Zenker diverticulum
- patients > 60y/o
- can enlarge – accumulate food (regurgitation, halitosis)
Complications: Aspiration pneumonia
Tx: Surgery
Esophageal: Midesophageal diverticulum is formed as a result of what?
Traction
- -adjacent inflammatory process
- -asymptomatic but can enlarge and cause issues
Esophageal: Describe venous drainage that causes varices
- Blood flow through the _____ is obstructed (e.g. cirrhosis)
- Blood flow diverts thorugh the _______ into the esophageal veins
- Results in abnormally dilated veins of the distal esophagus (a.k.a. varices)
- portal vein obstruction
- diverted through the left gastric to esophageal veins
- dilated distal esophageal veins (varices)
Esophageal: Esophageal varices are due to increased pressure or blood flow that results in dilated, tortuous vessels.
What is a complication?
–rupture with massive hematemesis (painless)
- high mortality
- major cause of cirrhosis-related morbidity and mortality
Esophageal: A linear mucosal laceration (tear) in the distal esophagus/proximal stomach. It is due to a rapid, large increase in gastric pressure.
It presents with severe vomiting/retching episode followed by hematamesis.
Mallory Weiss tear
- excessive OH or bulemia
- inc. gastric pressure = inc. pressure gradient across GE junction
Esophageal: ______ describes spontaneous perforation of the esophagus. It MC occurs from a sudden increase in intra-esophageal pressure caused by vomiting.
Boerhaave syndrome
Iatrogenic: endoscopic perforation MC
Esophageal: A patient presents with sudden onset of severe retrosternal (chest) pain and upper abdominal pain that radiates to the back. Patient admits pain is worse when he swallows.
On PE you note crepitus in the suprasternal notch and neck region + crunching sound on chest auscultation (Hamman). NO hematamesis.
You suspect
Boerhaave syndrome
What: Esophageal perforation (MC distally)
Due to: OH, Repetitive Vomiting (complication of esophageal….)
- crepitus: subcutaenous/mediastinal emphysema
- *NO hematemesis
Esophageal: A patient who is a chronic alcoholic presents with repeated episodes of vomiting and severe retrosternal pain that radiates to the back.
On PE you note crepitus in the suprasternal notch (subcutaneous/mediastinal emphysema) and crunching sounds on chest auscultation (Hamman).
What is a potential complication of this syndrome?
a. pneumomediastinum
b. mediastinitis
c. sepsis and shock
d. death
All of the above
Boerhaave syndrome
- transmural perforation of esophageal wall, distal 1/3 (left dorsolateral)
- high mortality with esophageal rupture
Esophageal: A crunching, rasping sound that is synchronous with a person’t heart beat. It is heard over the precordium.
Hamman’s sign
- due to the heart beating against air filled tissue (mediastinal air)
- *Boerhaave syndrome -pneumomediastinum
Esophageal: Bening neoplasms of the esophagus include
- ______: tumor of SM
- Lipma: tumor of fat
Leiomyoma
Esophageal: Malignant neoplasms include
- Adenocarcinoma
- Squamous cell carcinoma
____ occurs most often in black males. It is usually the proximal 2/3 of the esophagus. It is often associated with smoking and alcohol (synergistic effect)
Squamous Cell carcinoma
- high mortality
- progressive dysphagia
- weight loss (late)
- early lymph node metastasis
Esophageal: Malignant neoplasms include
- Adenocarcinoma
- Squamous cell carcinoma
_____ is the MC 1o esophageal cancer in U.S. It most often affects white males (>60 y.o) and is common in the distal 1/3 of the esophagus. It is often associated with Barrett’s esophagus, which induces intestinal metaplasia.
Adenocarcinoma
- high mortality
- progressive dysphagia
- weight loss (late)
- early lymph node metastasis
Esophageal: True/False - lack of serosa and extensive lymphatics allows esophageal cancer to spread early in the disease course
True
Esophageal: Because it arises in Barrett’s mucosa, adenocarcinoma occurs in the distal esophagus. Which of the following accurately describes the progression to cancer?
a. gastroesophageal reflux – metaplasia – low grade dysplasia – high grade dysplasia – adenocarcinoma
b. gastroesophageal reflux – low grade dysplasia – metaplasia – high grade dysplasia – adenocarcinoma
A
–reflux – meta – low grade – high grade – carcinoma
Esophageal: Contrast risk factors for adenocarcinoma and squamous cell carcinoma
Adenocarcinoma:
–smoking
Squamous cell:
- -smoking, alcohol
- -diet w/ few fruits/veg.
- -caustic ingestion
- -achalasia
Esophageal: True/False - Squamous cell carcinoma often occurs in the mid-esophageus causing strictures. It most commonly occurs in black males
True
Histo: THe major salivary glands are the parotid, submandibular and sublingual.
- The ____ gland (serous) empties into the oral cavity opposite the 2nd upper molar. Secretion is stimulated by PNS (CN 9)
- The ___ gland (mixed; mostly serous) empties into the oral cavity lateral to the frenulum of the tongue. Innervation is CN7 (facial; PNS).
- The ___ gland (mixed; mostly mucous) empties into the submandibular duct and directly onto the floor of the oral cavity. Innervation is CN7 (facial; PNS)
- parotid
- submandibular
- sublingual
Histo:
- Parasympathetic stimulation (Ach) stimulates secretion of what acinar cells?
- Sympathetic stimulation (NE) stimulates secretion of what acinar cells?
- _______ cells propel the product toward the excretory duct
- Serous
- Mucous
*myoepithelial cells = propel product toward excretory duct (actin filaments)
Histo:
- _____ ducts have low, cuboidal cells. They secrete HCO3- and absorb Cl-
- _____ ducts have cuboidal to columnar cells. They reabsorb Na and secrete K+/HCO3-. *hypotonic secretion
- Intercalated
2. Striated
Histo: The function of the mucosa is to protect, secrete (mucous, digestive enzymes) and absorb). It consists of 3 layers:
- Epithelium (changes depending on function)
- Lamina propria (CT; glands)
- Muscularis mucosa (SM)
What are the layers of the muscularis mucosa? What is its function?
2 layers: circular and longitudinal
fxn: localize movement of mucosa; absorption and secretion
Histo: The submucosa lies below the muscularis mucosa. It is a layer of dense irregular CT with blood vessels and lymphatics. It also contains nerve plexi (ganglions whose nerve cell body is outside of the CNS). Describe signalling of these plexi
*Meissner’s
- Visceral sympathetic sneosry
- PNS terminal ganglia
- Enteric (pre and post-PNS)
Histo: The muscularis externa is composed of 2 layers of SM (inner circular and outer long.). Enlargements of this layer forms sphincters, and it contraction of the circular muscle helps mix contents of the lumen.
It also contains blood, lymph vessels and nerves. Describe the signalling
Myenteric plexus (Auerbach)
- ganglions of post-ganglionic PNS
- enteric
NOTE: circular: compress/mixing; long. muscle shortens tube and propels contents
Histo: True/False - Enlargement of the inner circular muscle forms the sphincters and valves. These sphincters include:
- pharyngoesophageal (UES)
- Inferior (LES))
- pyloric
- ileocecal
- internal anal sphincter
True
Histo: The adventitia/serosa is the outermost layer of the gut. It is composed of dense, irregular CT.
- _______ is found on organs that are suspended. It is simple squamous (mesothelial) and is equivalent to visceral peritoneum.
- _____ covers regions of the tract not lined by serosa. It is found on organs that are attached to the body wall.
- Serosa
2. Adventitia
Histo: As the gut progresses caudally, we see a widened lumen, increased surface area, increased invaginations and evaginations (pits, crypts, villi) and which of the following?
a. goblet cells
b. basophilia
c. lymphoid tissue
all of the above
Histo: The esophagus is a fixed muscular tube connecting the pharynx and stomach. It starts at the level of the cricoid cartilage and descends post. to the trachea.
The UES is striated (sk muscle) and functions to what?
block movement of air into the esophagus
NOTE:
- thoracic esophagus: adventitia;
- part of abdominal esophagus: serosa
Histo: Describe the transition (histologically) from the esophagus to the stomach
Strat. squamous wet to simple columnar w/ pits and glands (invagination)
Histo: The gastric epithelium contains surface mucous cells. It also invaginates forming gastric pits (openings) and gastric glands (bottom of pits).
What do the glands secrete?
Mucous (appear cloudy)
- protection
- HCO3-
Histo: The following are cells of the fundic stomach. List their functions
- Surface mucous cells (line surface and gastric pits; simple columnar)
- Neck mucous cells (line neck; cuboidal)
- Chief cells
- Parietal cells
- Enteroendocrine cells
*Pyloric stomach = loss of parietal and chief (mucous only)
- Neck mucous
- -alkaline mucous
- -vagal stimulation - Parietal cells
- -apex directed toward lumen
- -HCL (protein digestion; converts pepsinogen to pepsin)
- -IF (binds B12 — absorption) - Chief cells
- -base of fundic glands (near muscularis mucosa)
- -basophilic
- -pepsinogen (activated pH < 5)
- -bactericide
PUD drugs: True/False - Mix of AlOH/MgOH antacids with or without simethicone can relieve symptoms of extra gas with fewer adverse effects (less diarrhea and constipation) than the respective Mg and Al only preparations
True
Histo: List the cells of the Small Intestines and their secretions
- Enterocytes
- Enteroendocrine cells
- Goblet cells
- Paneth cells
- Enterocytes
- - - Enteroendocrine cells
- Goblet cells
- - - Paneth cells
- -antibacterial (phagocytose gram - bacteria)
- -lysozyme (degrades bacterial cell wall; form pores in plasma membrane)
Histo: The transition from the esophagus to the stomach involves a change in epithelium. Describe the transition
Esophagus: stratified sq. wet
Stomach: simple columnar with pits and glands
–invagination
Histo: Paneth cells are located at the base of the glands of the small intestines. Describe their features and their secretions.
Features:
- -basophilic cytoplasm
- -acidphilic, apical secretory granules
Secrete:
- -lysozyme
- -defensins (anti-microbial)
- -phospholipase A2
- -TNF-Alpha
Histo: Enteroendocrine cells are found in both the stomach and the SI. They resemble neurosecretory cells of the CNS. They secrete basally, rather than into the lumen.
What are their secretions?
- somatostatin (inhibit gastrin)
- gastrin (inc. HCl)
- ghrelin (inc. GH; appetite; inhibits lipid metabolism and fat utilization)
- CCK – gallbaldder contraction; pancreatic enzyme secretion
- GIP – inc. insulin; dec. gastric acid
- VIP – inc. heart contractility; vasodilation
- motilin – inc. motility
Histology: HCl production is stimulated by gastrin (major path for stimulation), Histamine (H2 receptor) and Ach. Formation of HCl involves the movement of K+ into the cell — to the canaliculus lumen, back into the cell and out of the cell.
What are the steps in HCl production?
- Formation of carbonic acid
- -CO2 enters cell – H2CO3 – H+ + HCO3 - Cl- enters the cell (exchanged for HCO3)
- -anion exchange (basal surface)
- -Cl- enters canaliculus
- HCO3- enters capillaries (lamina propria) and mucus lining - Exchange K+ for H+
- -via H+/K+ ATPAse
- -H+ out of cell to lumen (canaliculus) - HCl formation
- -in canaliculus
Histo: What is the distinguishing feature of the pyloroduodenal junction?
Goblet cells scattered in gastric glands
Histo: The small intestine acts as the principal site of digestion and absorption. It is composed of the duodenum, jejunum and the ileum.
The duodenum wraps around the head of the pancreas. Bile and pancreatic enzymes enter the ______ of the descending duodenum.
posteromedial wall
NOTE: duodenum is retroperitoneal (serosa - anterior; adventitia - posterior)
Histo: Transverse, circular folds with a core of submucosa. They are found in the small intestine (primarily the duodenum) and aid in nutrient absorption.
*also known as finger-like projections with villi
Plicae circulares (valves of Kerckring)
- extend 1/2 to 1/3 around the circumference of the lumen
- most numerous in distal duodenum
NOTE: *villi contain lamina propria core and lacteals (blind ended lymphatic vessels)
Histo: Intestinal glands (crypts of Lieberkuhn) of the small intestine span the width of the lamina propria. They open onto the luminal surface at the base of the villi. They contain several different cells including:
- Enterocytes
- Goblet Cells
- Paneth Cells
- Enteroendocrine cells
_______ are small, columnar cells with microvilli that function mainly in absorption. They are joined to neighboring cells by tight junctions and act to move water across the cell.
Enterocytes
a. Water movement: via lateral Na/K+ ATPase
- -intercellular bridges (Na moves in apically; out laterally)
- -water follows
b. enzymes localized to apical membrane (microvilli)
- -enteriokinase (trypsinogen to trypsin)
- -trypsin cleaves/activates other enzymes
Histo: Intestinal glands (crypts of Lieberkuhn) of the small intestine span the width of the lamina propria. They open onto the luminal surface at the base of the villi. They contain several different cells including:
- Enterocytes
- Goblet Cells
- Paneth Cells
- Enteroendocrine cells
Enteroendocrine cells secrete hormones basally into the bloodstream (similar to those in the stomach, while Goblet cells (unicellular glands) contain large mucinogen granules apical to the nucleus. What do they secrete?
Mucin
(gets hydrated – protective gel coat – protects epithelial lining from abrasion and inhibits bacterial invasion
Histo: Histo: Intestinal glands (crypts of Lieberkuhn) of the small intestine span the width of the lamina propria. They open onto the luminal surface at the base of the villi. They contain several different cells including:
- Enterocytes
- Goblet Cells
- Paneth Cells
- Enteroendocrine cells
Paneth cells are unique to the glands of the small intestine (though can appear in large intestine for pathologies). They are found at the base of the intestinal gland and secrete apically into the lumen. What do they secrete?
- TNF alpha
- Lysozyme: degrades bacterial cell wall and forms pores in plasma membrane
- Defensins: + charge aa’s and hydrophobic aa’s to insert into membrane – pore – kills
- Receptors (on plasma membrane): endocytosis of macromolecules and gram - bacteria
- *antimicrobial cells
- acidophilic/eosinophilic granules
Histo: Histo: Intestinal glands (crypts of Lieberkuhn) of the small intestine span the width of the lamina propria. They open onto the luminal surface at the base of the villi.
They contain several different cells including Microfold (M) cells. M cells are located over lymphatic nodules (especially Peyer’s patches of the Ileum). They lack microvilli, but have apical membrane infoldings.
What is the function of M cells?
Transcytose antigens to underlying CT – deliver antigen to APC’s
Histo: What is a distingyishing feature of the duodenum?
Brunner’s glands
- -secrete alkaline (pH 8.8-9.3) mucous and HCO3-
- neutralizes acidic chyme (stomach)
- -provides correct pH for activation of digestive enzymes from the pancreas
Histo: The ileum and the jejunum have no submucosal glands. The jejunum has some lymphatic nodules, while the Ileum contains lymphatic nodules in the form of
Peyer’s patches
Small Intestine disorders: The function of the small intestine is to increase the surface area for absorption. It is composed of the following:
- Duodenum (Fe absorption)
- Jejunum (Folate absorption)
- Terminal ileum (B12 absorption)
Which part of the small intestine do you suspect to be affected in a patient with Down Syndrome (Trisomy 21) who presents with polyhydramnios, bilious vomiting, delayed passage of meconium and “double bubble” sign on radiograph?
Duodenal Atresia
- failure of canalization of the small bowel (a.k.a. complete occlusion or absence of a duodenal lumen)
- complete obstruction
- no gas distally, foaming at the mouth
- non-bilious vomiting if proximal to major duodenal papilla
NOTE: triple bubble sign = jejunal atresia (apple peel)
Small intestine disorders: ___ refers to incomplete obstruction of the small bowel that is caused by narrowing of the segment. It is less common than atresia
Stenosis
Small intestine disorders: ____ is characterized by persistence of the Vitelline (omphalomesenteric) duct. It follows the rule of 2’s:
- ~2 inches long
- 2 feet proximal to ileocecal valve
- 2 % of the population
- < 2 years old
Often presents asymptomatic, OR with painless hematochezia (lower GI bleed) with no signs of abnormalities on workup. It is considered a TRUE diverticulum.
Meckel’s diverticulum
*MC congenital malformation of the GI tract
*May contain heterotropic mucosa
(gastric MC – inc. risk of hemorrhage 2ndary to gastric acid)
NOTE: may present with RLQ pain; tarry stool
Small intestine disorders: A 15 month old female presents with grossly bloody diarrhea for 2 days. She has had a few episodes of blood tinged stools over the past 2 weeks. Her mother denies pain, nausea or vomiting. You note conjunctival pallor. Abdomen is soft and nontender. A small amount of dark red blood is present in her diaper.
You suspect
Meckel diverticulum
*Bleeding associated with heterotopic gastric mucose (inc. gastric acid = ulcers); Inc. risk Fe deficiency
NOTE: incomplete obliteration of omphalomesenteric duct.
Classic symptoms: Painless lower GI bleeding (hematochezia) in kids < 2 years; labs usually normal
Small Intestine disorders: A complication of Meckel’s diverticulum is intestinal obstruction. It can occur via attachment of the intestine to the abdominal wall by a fibrous band. A portion of the small bowel can then get wrapped around the band leading to volvulus. What can this lead to?
intussuception
Small Intestine disorders: A 2 year old male is brought to the clinic for dark stools. His parents report 2 days of black, jelly like stool in his diaper. He has not been irritable or shown any signs of distress or pain.
The abdomen is soft and nontender with normal bowel sounds. You suspect Meckel’s diverticulum. How do you diagnose Meckel’s diverticulum?
Laparoscopy/Laparotomy
*Technetium scan (injected IV – accumulation in the gastric mucosa over time)
Small Intestine disorders: There are different causes of bowel obstruction including:
- herniation
- adhesions
- volvulus
- intussusception (intestine telescopes into itself)
What are radiographic findings indicative of bowel obstruction?
- bowel distension
- air/fluid levels with step ladder appearance
- -absence of air distal to obstruction
Small intestine disorders: What are signs/symptoms of bowel obstruction?
a. abdominal pain
b. bilious vomiting
c. constipation
d. no rebound tenderness (no peritonitis)
all of the above
- abdominal distension
- *non-bilious emesis if PROXIMAL to ampulla of Vater
Small Intestine Disorders: A patient presents with colicky abdominal pain, constipation and vomiting. You note abdominal distension.
PMH Abdominal Surgery
You suspect the development of
Adhesions
- fibrous bands between loops of bowel.
- MCC small bowel obstruction
- secondary to peritoneal inflammation (previous surgery)
Small Intestine disorders: A protrusion, bulge or projection of an organ or a part of an organ through the body wall that normally contains said organ.
Clinically you see:
- swelling or fullness at site
- heavy, aching sensation (radiates to area)
- no true pain or tenderness on PE
- enlarges w/ increasing pressure (cough, lifting)
Hernia
Small Intestine disorders: Distinguish between an indirect and a direct hernia. How do these differ from a femoral hernia?
- Indirect
- -strikes distal tip of finger
- -superolateral to inferomedial
- Indirect Lateral to Inferior Epigastric
- processus vaginalis - Direct
- -strikes pad of finger (deep to superficial)
- Medial to Inferior Epigastric
- weakened transvers fascialis?
- regresses when reclined - Femoral hernia
- -bulge felt below inguinal ligament
Small Intestine disorders: Indirect inguinal hernias can form as a result of increased intra-abdominal pressure (e.g. coughing, lifting heavy weights) or from abdominal wall weakness.
It is MC associated with obesity, the male gender, and weight lifting. How does it differ in pathogenesis b/t adults and kids?
- Kids
–peritoneal connection persists
(inguinal canal and tunica vaginalis) - Adults
- -weak peritoneum
- -small bowel passes through internal inguinal ring —through ext. inguinal ring – scrotal sac
Small Intestine disorders: The triangle of Hesselbach is composed of:
- Medial: rectus abdominis
- Lateral: Inf. epigastric artery
- Inferior: Inguinal (puopart’s ligament)
Indirect Inguinal Hernias occur outside of Hesselbach’s triangle. They ENTER the inguinal canal lateral to the ______ and EXIT the inguinal canal inferior to the ______.
- ENTER - lateral to inf. epigastric
2. EXIT - inferior to inguinal lig.
Small Intestine disorders: The triangle of Hesselbach is composed of:
- Medial: rectus abdominis
- Lateral: Inf. epigastric artery
- Inferior: Inguinal (puopart’s ligament)
Direct Inguinal Hernias occur within Hesselbach’s triangle. They tend to breach the posterior inguinal wall and pass medial to the _________ vessels.
pass medial to inf. epigastric vessels
Clinical:
- -bulges in proximity to ext. inguinal ring
- disappears when patient reclines
- rarely incarcerates
Small intestine disorders: A 31 year old female presents with peritoneal outpouching that extends into the femoral canal (medial to the femoral vein).
On PE you note absent scrotum involvement. It is not felt by the finger in the inguinal canal.
You suspect
Femoral hernia
- MC females
- highest rate of incarceration of the small bowel
- due to: narrow femoral ring
NOTE:
- never involves scrotum
- not felt by finger in inguinal canal
Small intestine disorders: _____ in children occurs from an opening in the linea alba, which develops when the umbilical scar fails to heal at birth. It is MC in African American children. Most will close in the 1st 12-13 mos of life.
Umbiical hernia
kids: opening in linea alba
adults: acquired; inc. intra-ab pressure (pregnancy, obesity); MC females
Small Intestine disorders: _____ describes a hernia in the area of previous surgical incision (a.k.a. incisional hernia).
Risk factors include anything that inhibits natural wound healing (e.g. infection, excessive wound tension, poor technique and obesity)
Ventral hernia
*obesity - creates tension on abdominal muscles
Small Intestine disorders: ____ describes loops of bowel caught between adhesions that result in compromise of blood supply and subsequent infarction.
Internal hernia
Small intestine disorders: complications of hernias include incarceration and strangulation.
- ______ is due to compromise of blood flow to the herniated bowel. (leads to hemorrhagic infarction/ischemic bowel).
- _____ is a hernia that cannot be reduced (spont. or mannually) thorugh the defect in the fascia. Associated with nausea, vomiting, bowl obstruction symptoms.
- Strangulation
2. Incarceration
Small Intestine: _______ occurs in elderly females. It is due to inflamed gallbladder that adheres to the small bowel and develops a fistula.
It can present with intermittent small bowel obstruction, presence of gallstones in the iliac fossa, and pneumobilia (gas in biliary tract).
Gallstone ileus
*gallstones pass through fistula
Small intestine: ________ occurs when a segment of bowel becomes twisted on itself. It occurs in areas with redundant mesentery (small bowel, sigmoid or cecum).
Patients present with abdominal pain, distension, bilious vomiting or ischemia (gnagrene, tachycardia, hypotension and hematochezia).
Labs reveal:
- Whirl sign or coffee bean sign and dilated loop of bowel (adults)
- Cork-screw duodenum kids
- Malpositioned duodenojejunal junction
Volvulus
- restricts blood supply – abdominal pain (infarction)
- bowel obstruction - bilious emesis
- Sigmoid MC adults, Midgut and Malrotation MC kids
Small intestine: _______ is a proximal segment of bowel (intussusceptum) that invaginates into the distal segment (intussusipiens). Peristalsis tends to pull the mesentery with it.
Intussusception
complications: obstruction and infarction
due to: Meckel, peutz-jegher, Peyer’s patches
Small intestine: What is believed to be the nidus for intususception in kids (MC < 5 y/o)?
a. polyp
b. cancer
c. lymphoid hyperplasia of Peyer’s patch
d. weight lifting
C - lymphoid hyperplasia of Peyer’s patch
*2ndary to viral infection (rotavirus vaccine)
Adults:
–polyp or cancer
Small Intestine: A 4 year old child presents to the clinic with his concerned mother. She states that her son has been vomiting, and has been “colicky” with severe and intermittent abdominal pain. She confirms that he has had dark red, gelatinous “currant jelly” stools. She reports the “attacks” have been occurring every 15-30 minutes.
You note emptiness/retraction in the RLQ “Dance sign” on PE.
You suspect
Intussusception
*MCC Meckel diverticulum, Enlarged Peyer’s patches (rotavirus, adenorus, IgA vasculitis), Puetz Jegher
Clinical Triad: abdominal pain, palpable sausage-shaped mass and “currant jelly stools” (mucous + sloughed mucosa + shed blood)
Dx: Ultrasound
Intestinal disorders: Disaccharide enzymes are located in the brush border of the SI villi. These enzymes aid in digestion of disaccharides into sugars.
Lactase deficiency (disaccharidase deficiency) is a malabsorption syndrome characterized by inability to digest lactose. This results in abdominal pain, flatus, and osmotic diarrhea upon ingestion of dairy products. Distinguish b/t primary and secondary deficiencies.
Primary:
- -genetic loss of lactase
- -MC non-white
Secondary:
- -viral infections of SI (damage villi – self-limited deficiency)
- -celiac disease
Intestinal disorders: Pancreatic insufficiency occurs when > 90% of pancreatic exocrine function is lost. Loss of pancreatic enzymes (amylase and lipase) can lead to fat malabsorption.
What are clinical features of pancreatic insufficiency? What are common etiologies?
Clinical:
- -steatorrhea (loose, greasy, fould smelling stools)
- -deficiencies of fat-soluble vit. (ADEK)
- -loss of proteases (protein malabsorption)
Etiologies: CF, Chronic pancreatitis, Pancreatic duct obstruction (cancer)
Intestinal disorders: ________ (sprue; gluten sensitive enteropathy) is due to an autoimmune reaction triggered by environmental agent (gliadin component of gluten) in genetically pre-disposed individuals.
It is common and is associated with IgA antibodies to gliadin, endomysium and tissue transglutaminase.
Celiac disease
- IgA to gliadin, endomysium, tissue transglutaminase
- HLA-DQ2 and/or HLA-DQ8 +
Intestinal disorders: In genetically susceptible individuals with celiac disease, ingestion of food containing gluten (wheat, barley, or rye) induces an immune reaction.
deamidated Gliadin and tissue transglutaminases are presented to helper T-cells by APC’s. These T-helper cells mediate inflammation by releasing IFN and triggering B-cells to make autoantibodies.
What is the net result?
-destroyed villi – dec. surface area – malabsorption
- gliadin presented to HLA DQ2 or HLA DQ8 on APC
- Stimulate CD 8 T-cells (IL-15)
- B cells and cytokines = tissue production
Intestinal disorders: Patients with celiac disease typically present with manifestations due to malabsorption, including:
- nutritional deficiencies (B12, iron, folate, Ca2+)
- weight loss
- diarrhea
- flatulence
- weakness/fatigue (2ndary to nutritional deficiency/anemia
- -osteoporosis
What are histological features of celiac?
- Loss of villi (villous atrophy) crypt hyperplasia
- increase intra-epithelial T-cells
*villi may be flattened (less surface area for absorption)
Small intestine disorders: Which of the following is an association of celiac disease?
a. dermatitis herpetiformis
b. Down syndrome
c. selective IgA deficiency
d. autoimmune disorders (type 1 diabetes mellitus, thyroiditis)
all of the above
- derm. herpetiformis
- -autoimmune
- -blisters
Small intestine disorders: _______ is associated with celiac disease. It is an autoimmune blistering disorder that results from an immunologic response to chronic stimulation of the gut mucosa by dietary gluten.
It presents as grouped vesicles (analagous to herpes; “herpetiformis”).
Dermatitis herpetiformis
*IF - IgA autoabs at tips of dermal papillae
Small intestine disorders: Which of the following is true about celiac disease?
a. increased incidence in 1st degree relatives
b. high incidence in whites, low in blacks and asians
c. increased risk for adenocarcinoma and lymphoma
d. may have antibody testing or biopsy for confirmation
e. histology reverts to normal if started on gluten-free diet
All of the above
Dx:
- Ab testing
- -IgA anti-tissue transglutaminase ab (IgA tTG) **screen
- -anti-endomysial ab - Biopsy
- -confirm
- -distal duodenum/proximal jejunum (**highest conc. of gluten)
* crypt hyperplasia, villous atrophy
Small intesting disorders: True/False - All patients express the HLA-DQ2 or HLA-DQ8 allele, however, only minority of people who express DQ2/DQ8 have celiac disease. Absence of these alleles excludes the diagnosis of celiac disease
True
Small intestine disorders: Treatment for celiac disease includes starting the patient on a gluten-free diet and correcting the nutritional deficiencies.
If a patient who was previously doing well on gluten restriction is no longer responsive to the gluten restriction, what must be considered?
malignancy
*small intestinal lymphoma
Histo: The large intestine joins the small intestine at the ileocecal junction. It functions to resorp H2O and electrolytes as well as eliminate waste. Two of the distinguishing features include taniae coli (colon and cecum) and NO villi (surface amplification).
What are other features of the large intestine?
a. absence of plicae circulares
b. absence of paneth cells in glands
c. absence of digestive enzymes
d. increased goblet cells
e. microfold cells
all of the above
4:1 enterocyte to goblet cell
(absorption, lubrication - mucous, NO digestion)
- muscularis externa w/ taenia coli (longitudinal muscle; 3 bands)
- haustra - localized sacs (contraction) of the taenia coli
Histo: True/False - The outer longitudinal layer of muscularis externa of the large intestine is composed of taenia coli, 3 thickened, equally spaced bands of smooth muscle. Contraction of this smooth muscle forms haustra.
Taenia coli are NOT found in the rectum, anal canal or appendix.
True
- contractions of inner circular: segmentation (local)
- contractions of circular and longitudinal: peristalsis (distal mass movements)
Histo:
- ____ small blind pouch of large intestine that is histologically identical to the colon.
- ____ slender, blind diverticulum of the cecum. It is small with an irregular lumen. It contains cellular debris.
- Cecum
- -ileocecal junction - Appendix
- -uniform outer long. layer
- -lots of lymphatic nodules (Peyer’s) in submucosa
- -lymphocytes!
*intestinal glands, enterocytes, goblet cells
Histo: The ______ is the dilated distal portion of the alimentary canal. It has transverse rectal folds that help to distinguish the upper region from the rest of the distal colon.
The mucosa of the rectum is similar to the distal colon with straight tubular glands and lots of goblet cells (1:1 enterocyte to goblet).
Rectum
Histo: The anal canal is the most distal region of the alimentary canal. It is composed of longitudinal folds of mucosa in the upper region known as ____1___. It also contains depressions between these columns known as ___2___.
Mucus anal glands open into the anal sinuses. When compressed by fecal material, these sinuses exude mucous.
- anal columns
2. anal sinuses
Histo:
- Zone of the anal canal that is composed of simple columnar with goblet cells
- Zone of the anal canal that transitions from columnar – strat squamous wet epithelium.
- Zone of the anal canal that is composed of stratified squamous dry epithelium
- Colorectal zone (upper 1/3)
- Anal transitional zone (pectinate line)
- Squamous zone (lower 1/3)
- superior to pectinate line - derived from embryonic hindgut (endoderm)
- inferior to pectinate line - derived from embryonic proctodeum (ectoderm)
NOTE: above - superior rectal artery, portal system, internal iliac LNs
NOTE 2: Below - middle and inferior rectal, caval system, superficial inguinal, pudendal nerve (sensitive to pain)
Histo: The submucosa of the large intestine contains thin-walled branches of the superior rectal artery and rectal venous plexusa.
Explain the clinical types of bleeding in association with the pectinate line
- Superior to line:
- -internal hemorrhoids
- -intact musc. mucosa - Inferior to pectinate
- -external hemorrhoids
Histo: The internal anal sphincter is formed by the _____ layer of the muscularis externa of the large intestine
inner circular SM
- inner circu. thickens at the pectinate line
- SNS = inc. contraction
- PNS = inhibit contraction; inc. distension (movement of feces)
Histo: The external anal sphincter is formed by _____ of the muscularis externa. It is under voluntary control and is the inferior 2/3 of the anal canal.
Skeletal muscle
*inf. to pectinate line
Histo: The entire anal canal is embedded in surrounding CT (Adventitia). Blood supply and innervation is based upon association with pectinate line.
- Describe blood supply/innervation superior to pectinate
- Describe blood supply/innervation inferior to pectinate
- Superior
Nerve: visceral motor = stretch sensitive
Lymph: internal iliac nodes
Supply: IMA and exits hepatic portal - Inferior
Nerve: somatic motor and sensory (parietal; pain, touch, temp)
Lympy: superficial inguinal nodes
Supply: Internal Iliac to IVC
NOTE: SNS: maintains tonus (contraction); PNS inhibits tonus
Histo: True/False - Portal hypertension induces internal hemorrhoids
True
Small intestine disorders: ______ is only found in certain (tropical areas of the world). Manifestations of this disorder are similar to those of celiac disease: chronic diarrhea, steatorrhea, weight loss and nutritional deficiencies.
Biopsy findings include:
- villous damage/inflammation
- NOT confined to proximal small bowel (unlike celiac)
- damage to jejunum (folate deficiency)
- damage to ileum (B12 deficiency)
It is thought to occur from infection (b/c it is responsive to antibiotics).
Tropical sprue
Dx:
- -abnormal SI biopsy in an individual with chronic diarrhea and evidence of malabsorption
- *reside in tropical country
Small intestinal disorders: Growth of colonic type bacteria (E. coli, Bacteroides) within the small intestine.
It most often occurs from impaired peristalsis (scleroderma) or changes in intestinal anatomy (Crohn’s w/ fistula formation b/w small and large bowel)
Bacterial overgrowth
Clinical:
- -B12 def (bacteria use)
- -Steatorrhea (deconjugate bile acids – more quickly absorbed and not digestable)
- -diearrhea (due to steatorrhea and inc. fluid secretion from bacterial enterotoxins)
Small intestine disorders: A rare, multi-system disorder with insidious onset of diarrhea, steatorrhea and weight loss.
It is MC due to SI involvement of Tropheryma whippelii, which causes malabsorption of fat. Lacteals get compressed by foamy macrophages containing the organisms.
Whipple disease
MC middle aged white men
*can involve other tissues (synovial tissues; arthralgia or CNS; dementia)
**Cardiac, Arthralgias, Neurologic, PAS (+) macrophages (foamy)
SMall intestine disorders: Whipple disease can be ID’d based on the presence of bacteria, and the irregular fold patterns and thickened walls of the SI. Describe treatment and prognosis of whipple disease
Treatment:
–DS TMP-SMX 1x year
Prognosis: death within one year without treatment
Small intestine disorders: Most of the SI is supplied by the SMA. Infarctions may occur leading to ischemia.
Types include:
- ____: a full-thickness infarct that affects the entire wall. It is usudally due to embolism or thrombosis of the SMA.
- ____: usually occurs 2o to hypoperfusion (shock)
- transmural
2. superficial
Small intestine disorders: Most of the SI is supplied by the SMA. Infarctions may occur leading to ischemia. Causes of acute ischemia include
- Acute vascular obstruction
- Non-occlusive ischemia
- Mesenteric vein thrombosis
What are examples of each?
- Acute vascular obstruction
- embolism from heart (a-fib),
- -aorta (atherosclerotic plaque), aortic aneurysm, SMA thrombosis - Non-occlusive ischemia
- -shock - Mesenteric vein thrombosis
- -hypercoagulable state, tumors
Small intestine disorders: A patient presents with sudden onset severe abdominal pain and bloody diarrhea.
On PE you note absent bowel sounds (ileus) with NO rebound tenderness (peritonitis).
Labs reveal:
- Profound neutrophilic leukocytosis
- Positive stool guaiac
- “thumbprint” sign on CT
What do you suspect?
Small bowel infarction
Dx: Abdominal CT **
- -“thumbprint sign” (edema in bowel wall)
- -bowel distension w/ air or fluid levels similar to obstruction
Small intestine disorders: Diverticular disease is uncommon in the small bowel, but if it occurs, it is MC in the duodenum.
It is associated with systemic sclerosis, and can result in _____ due to bacterial overgrowth.
B12 deficiency
Small intestine disorders: A 2 week old, low birth weight infant is brought into the ER due to bloody stool.
On PE you note abdominal distension and presence of gas in the intestinal wall (pneumatosis intestinalis).
You admit the patient and refer to surgery for resection because you suspect
Necrotizing enterocolitis
- ischemic necrosis of small/large intestine
- premature, low birth weight infants
COmplications:
- -transmural necrosis w/ perforation and peritonitis
- -strictures from healing
Treatment:
–resect damaged segment
Prognosis:
–high mortality
Small intestine: The MC malignancy of the small bowel is metastatic disease. Primary malignant tumors of the small bowel include:
a. carcinoid tumor within the terminal ileum
b. adenocarcinoma in the duodenum or proximal jejunum
c. malignant lymphoma in the terminal ileum
d. duodenal carcinoma
A-C
- Carcinoid:
- -ileum or more proximal
- -MC 1o malignancy of SI - Adenocarcinoma
- -rare
- -MC ampulla of Vater
- -inc. risk with FAP - Malignant lymphoma
- -B cell origin (extra-nodal marginal zone; MALT)
- -T cell if secondary to celiac
Small Intestine disorders: Tumor of neuroendocrine origins that can be potentially malignant (depends on presence of metastasis).
It is characterized by monotonous sheets and nests of small round cells with uniform nuclei and absent to rare mitotic figures.
Carcinoid tumor
- -immunohistochemical stain: chromogranin
- -more likely malignant wit inc. size (>2cm)
*small bowel carcinoids = more likely to metastasize than stomach/rectum
Small intestine disorders: Carcinoid syndrome is possible when a carcinoid tumor has metastasized to the liver. Normally, serotonin (5HT) from the tumor travels to the liver through the portal circulation, where it is metabolized to 5-HIAA.
What occurs in the case of metastatic tumor nodules?
5HT is directly secreted into hepatic vein tributaries (systemic circulation)
Small intestine disorders: A 41 year old female presents to the clinic with intermittent wheezing, episodic facial flushing, abdominal cramps and secretory (watery) diarrhea.
Past medical history includes cardiac valvular abnormalities (tricuspid insufficiency or pulmonary stenosis) and heart disease (mainly R. sided heart fibrosis).
Imaging reveals a mass in the small bowel (MC ileum). Histology reveals prominent rosettes composed of numerous small monomorphic cells with salt and pepper chromatin. Cells stain positive for synaptophysin, chromogranin A and neuron specific enolase (NSE).
What do you suspect?
Carcinoid tumor
–5HT (Inc. 5HIAA)
- flushing of the skin (2ndary to vasodilation)
- -warmth
- -stress, OH, exercise, cheese
- -5HT inc. bowel secretions/motility
NOTE: Neuroendocrine tumor (enterochromaffin cells of GI, B-cells of pancreas)
Small intestine disorders: Carcinoid heart disease is a common complication of carcinoid syndrome. It is caused by fibrotic plaques of the R. sided heart valves (not L. sided because MAO in the lung metabolizes 5HT to inactive 5HIAA).
Carcinoid heart disease primarily results in what?
- tricuspid regurg.
- -high pitched, holosystolic murmur at left lower sternal border) - pulmonary stenosis
Small intestine disorders: True/False - Adenomatous polyps that are dysplastic (pre-cancerous) can be a risk of transformation into adenocarcinoma
True
Inflammatory Bowel: IBD encompasses Ulcerative colitis and Crohn disease.
Under physiologic conditions, homeostasis normally exists b/t the commensal microbiota, intestinal epithelial cells and the immune system. In the case of UC and Crohn, disruption of these relationships via genetic factors or environmental factors has occurred.
True
*disrupt homeostasis – inflammation (IBD)
IBD: Inlammatory bowel disease affects a wide age rang, but peak incidence occurs in the 2nd to 4th decades. It affects males and females equally, but is most prominent in white urban populations (esp. Jewish).
Manifestations depend on the area of the tract involved, but MC include cramping, abdominal pain, diarrhea +/- passage of mucous or blood. What is unique about these symptoms?
Wax and wane in intensity
- symptomatic: active stage
- asymptomatic: Inactive stage
IBD: Ulcerative colitis always involves the rectum (usually starting point) and progresses in a continuous fashion.
What are the major symptoms of ulcerative colitis?
a. rectal bleeding
b. tenesmus
c. passage of mucous
d. cramping/abdominal pain
All of the above
- rectal bleeds
- -fresh blood/blood stained mucous
- -may be mixed with stool or streaked onto the surface of the stool - Tenesmus
- -urgency with a feeling of incomplete evacuation
NOTE: severity of symptoms correlates with extent of disease. May present acutely, but MC chronic symptoms.
IBD: On imaging, ________ can appear with erythematous finely granular inflamed mucosa. It may bleed depending on severity of inflammation.
Lead pipe sign (loss of haustra) also key finding
ulcerative colitis
IBD:
- Ulcerative colitis is limited to what structure?
- Describe the inflammation
- What is the cancer risk?
- Limited to colon/rectum
- -starts at anal verge (involves rectum)
- -may remain confined there, or proximal contiguous extension
* NO skip lesions - Superficial, NO granulomas
- -ulceration = bleeding, fluid/electro loss
- -activity waxes and wanes (trigger = psychological stress) - After 8-10 years, substantial inc. risk of colon cancer
* colonoscopy and surveillance biopsy every few years
IBD: True/False - With ulcerative colitis, intestinal manifestations are surgically curable. However, extra-intestinal manifestations persist.
True
*Perinuclear anti-neutrophil cyoplasmic antibody (pANCA) may be elevated
IBD: Complications of Ulcerative colitis include
a. massive hemorrhage with severe attacks
b. toxic megacolon
c. perforation leading to peritonitis
d. strictures due to scarring
e. colon cancer
all of the above
- massive hemorrhage
- may require colectomy - megacolon - massive dilatation;
- -half resolve with therapy
- -if doesn’t resolve = urgent colectomy - perforation - associated with toxiic megacolon
- -inc. mortality - Colon cancer
- -esp. long standing (> 10 years) and extensive disease (>50% colon involvement)
IBD: A patient presents complaining of abdominal pain and cramping. He states he has bloody stool.
Gross findings reveal “inflamed colonic mucosa with “pseudopolyps”
Labs reveal elevated P-ANCA
You suspect
Ulcerative colitis
- areas of regenerating mucosa projecting into the lumen
- continuous involvement - no skip areas
Unlike UC, which only involves the colon/rectum, Crohn disease can onvolve any region of the GI tract (mouth to anus - MC terminal ileum and ascending colon).
The site of the disease influences the clinical presentation (more variable manifestations than in UC).. However, Crohn’s commonly presents with diarrhea and inflammation. Describe the inflammation compared to UC
full-thickness (transmural)
*inc. risk fibrosis (strictures, obstruction), fistulae and perianal obstruction
IBD: Although Crohn’s can involve any region of the GI tract, the most common sites affected are
Terminal ileum +/- ascending colon
*iliocolitis: chronic Hx of recurrent R. lower quad pain and diarrhea (may mimic acute appendicitis)
IBD: Crohn’s disease is most common in what populations?
Whites (eastern European) or Ashkenazi Jews
- 2 peaks of incidence: teens - 20s; 60-70
- slightly more common in males
IBD: Which of the following does NOT describe Crohn’s disease?
a. Only involves the rectum
b. Skip lesions
c. transmural
d. granulomas are characteristic
A - only involves rectum
- any segment of GI (often spares rectum)
- perianal complications (pain, abscesses, drainage)
- skip lesions (periodic remissions/exacerbations; inflammation)
*granulomas (macrophages)
IBD: Granulomas are characteristic of Crohn’s disease. They are not surgically curable, and recurrences are common.
How are they detected? What is their significance?
*inc. risk of colon cancer (less than UC)
detection:
–Anti-saccharomyces cerevisiae antibody (+
ASCA +)
IBD: What are (characteristic) gross/lab findings of Crohn’s?
Gross:
- cobblestoning (disease tissue below normal mucosa)
- creeping fat (narrowed lumen – fat pulled with it around bowel wall)
Endoscopy:
- -stricture
- -“string sign”
- healing w/ fibrosis = thickened bowel wall w/ narrowed lumen
Histology:
–granulomatous inflammation (non-caseating/non-necrotic)
IBD: True/False - True/False - The transmural nature of the inflammation in Crohn’s disease usually leads to Increased risk of obstruction and fistula formation. Obstruction occurs from decreased luminal diameter due to fibrosis, whereas fistulae formation occurs from ulcers extending into deeper tissue.
True
*segmental nature results in gaps of normal or dilated bowel b/t involved segments
IBD: Common complications of Crohn’s disease are malabsorption of bile salts and vitamin B12.
Bile salts are normally absorbed in the distal ileu. Depletion of the bile salt pool can lead to risk of fat malabsorption and ultimately the development of ____
steatorrhea
- contributes to other issues:
- -malnutrition, weight loss
- -hypocalcemia, clotting, osteomalacia
- -pigment gallstones (reduced bile acid:cholesterol ratio = lithogenic bile)
IBD: Toxic megacolon is due to acute, severe colitis with markedly dilated colon (non-obstructive colonic dilatation >6cm).
It is a medical emergency, and has a high risk of perforation (lethal). It is most commonly associated (but not specific to) which bowel disorder?
Ulcerative colitis
IBD: True/False - Both IBD syndromes can occur with extra-intestinal manifestations. Arthritis is more common in patients suffering from Crohn’s disease, whereas primary sclerosing cholangitis is most often seen in ulcerative colitis patients.
True
Gastric disorders: Protective factors of the stomach include:
- mucin (secreted by surface foveolar cells) which forms a barrierr
- HCO3- (neutralizes pH)
- Gastric epithelial cells (replaced every few days; form barrier and limit back diffusion)
- Blood lfow (O2, nutrients and washes away back-diffused acid)
Prostaglandins also play a major role in protection of the stomach. They do so by regulating what?
HCO3- secretion, mucosal blood flow and epithelial regeneration
NOTE: NSAIDs act by inhibiting COX-1 – dec. prostaglandins – degrade protective ability of stomach
Gastric disorders:
- ____ describes vomiting of blood. The MC causes are Gastric and/or duodenal ulcers (PUD). Gastritis, esophagitis, Mallory Weiss can also contribute.
- ____: black tarry stool. Presence indicates an upper GI bleed
- Hematemesis
- Melena
- -proximal to duodeno-jejunal jxn (ligament of Treitz)
- -Hb converted to hematin (black pigment) by acid
Gastric disorders: Gastric acid can be analyzed using Basal acid output (BAO) and Maximal acid output (MAO). BAO is output of gastric fluid that is collected via NG tube over a 1 hour period on an empty stomach, whereas, MAO describes fluid collected over 1hr following pentagastrin administration.
What would you expect these values to look like in a patient with gastric ulcers? duodenal ulcers?
- Gastric
- -normal or decreased BAO, MAO - Duodenal
- -increased BAO and MAO
Gastric disorders: Progressive hypertrophy of the circular muscles of the pyloric sphincter is characteristic of ________. It is not present at birth, but occurs over the ensuing 3-5 weeks. It is believed to be due to genetic dysfunction.
Clinical presentation includes:
- non-bilious, projectile vomiting
- palapable “olive” abdominal mass (thickened pylorus)
- visible hyperperistalsis
Infantile Hypertrophic Pyloric stenosis
- MC males and siblings
- hungry eater
Dx: Abdominal ultrasound
Tx: pyloromyotomy – split muscle layer to relieve obstruction
NOTE: stenosis can be acquired secondary to scarring from PUD
Gastric disorders: Delayed gastric emptying of food that results in early satiety, nausea and vomiting of undigested food after eating.
It is commonly idiopathic, but may be due to autonomic neuropathy, post-vagotomy, or Ach medications.
Gastroparesis
Gastric disorders: Damage to the gastric mucosa with erosion and subsequent hemorrhage.
It is caused by direct toxicity and/or mucosal ischemia that leads to mucosal injury enabling entry of gastric acid or pepsin to penetrate the mucosa.
Acute hemorrhagic erosive gastropathy
- acid penetrates mucosa
- MC alcoholics (direct toxic effect)
Other etiologic agents: cancer chemo; caustic ingestions (acid or alkali); iron pills (mucosal necrosis, erosions, ulcers); cocaine (vasoconstriction of mesenteric vasculature - ischemia)
Gastric disorders: Stress ulcers are associated with severe physiologic stress (e.g. trauma, burns, major surgery).
There are two main Pathogenesis:
- Ischemia secondary to decreased mucosal blood flow
- Increased vagal stimulation
Explain
- Ischemic injury
- -systemic hypoperfusion (shock)
- -hypovolemia due to severe burns (Curlings ulcer) - Vagal stimulation
–CNS injury or disease (inc. intra-cranial pressure) – inc. vagal outflow – parietal cell activity – inc. acid
(Cushing’s ulcer)
Gastric disorders: Peptic ulcer disease (PUD) describes a defect in the gastric or duodenal mucosa that extends through the muscularis mucosa into the deeper layers of the wall.
Many present without symptoms, or present following the onset of complications (hemorrhage or perforation). Some present with upper abdominal (epigastric pain).
What are common etiologies of ulcers? What is MCC?
- H. pylori ***
- -declining prevalence of infection
- -eradication reduces recurrence
* smoking - NSAIDS
- Severe stress (life-threatening illness)
- Excess gastric acid (Zollinger Ellison)
NOTE: duodenal ulcers MC than gastric; avoid smoking and OH
Gastric disorders: A 41 year old patient presents complaining of burning “gnawing” epigastric pain. He states it improves when he eats, but is worse about 2-5 hours after meals. He also complains the pain is worse at night. The previous describes what type of ulcer?
Duodenal
- Worse – when acid is secreted in absence of food to buffer
- worse at night - max circadian acid secretion
Gastric disorders: A 36 year old female presents to the clinic complaining of epigastric pain that worsens when she eats. She complains of weight loss and nausea. This describes what type of ulcer?
Gastric ulcer
Gastric disorders: The following gross and microscopic findings describe what disorder?
Gross: Well circumscribed with slight elevation around the edges “punched out lesions”
Microscopic:
- necrotic debris with neutrophils
- heals with scarring (fibrosis)
Peptic ulcer disease
Scarring = inc. risk gastric outlet obstruction
NOTE:
- Gastric ulcers = Biopsy ** (due to risk of ulcer being caused by gastric cancer)
- Duodenal ulcers = no biopsy needed; not malignant
Gastric disorders: Complications of PUD include:
- Hemorrhage (MC)
- Perforation
- Gastric outlet obstruction
____ is the MC complication. It may be significant/lethal. Increased risk is in older adults. It presents with melena, hematamesis and “coffee ground” emesis.
Hemorrhage
- coffee grounds
- Inc. BUN (absorption of proteins; pre-renal azotemia)
NOTE: gastric bleeds - left gastric artery; duodenal bleed – gastroduodenal artery
Gastric disorders: Complications of PUD include:
- Hemorrhage (MC)
- Perforation
- Gastric outlet obstruction
____ is the 2nd MC complication. It presents with sudden onset of severe, sharp, abdominal pain (generalized) with “acute abdomen”. Free air is seen on imaging.
Perforation
- acute abdomen: rigidity, guarding, rebound tenderness)
- free air
*can lead to: peritonitis, sepsis, hypotension, pancreatitis (if duodenal)
Gastric disorders: Complications of PUD include:
- Hemorrhage (MC)
- Perforation
- Gastric outlet obstruction
____ narrowing of the outflow tract due to edema/inflammation of the pylorus. It presents with early satiety, vomiting and weight loss.
Gastric outlet obstruction
*complications: dehydration, metabolic alkalosis
Gastric disorders: _____ is a gram (-) curved rod that lives within the gastric mucosa (antrum).
It is transmitted by fecal-oral or oral-oral routes (organisms in stool or vomit). It acts by disrupting the mucous layer and liberating enzymes and toxins, making the mucosa more vulnerable to acid injury.
H. pylori. (MCC PUD)
may cause:
- asymptomatic
- -PUD
- -gastric atrophy (intestinal metaplasia/gastric carcinoma)
- -persistent stimulation of MALT (inc. risk gastric lymphoma)
Gastric disorders: True/False - Chronic H. pylori gastritis is usually asymptomatic, however, in some cases, altered gastric secretion + tissue injury leads to PUD.
It may occasionally lead to gastric atrophy, intestinal metaplasia, and eventually gastric carcinoma.
True
*OR persistent stimulation of lymph may lead to gastric lymphoma
Gastric disorders: True/False - Host immune response further perpetuates tissue injury in H. pylori infections.
The chronic inflammation induced by H. pylor upsets gastric acid secretory physiology to varying degrees.
True
Gastric disorders: Which of the following is a mechanism that enables H. pylori to survive in the stomach?
a. flagella
b. urease
c. adhesins
d. exotoxins
A-C
flagella: swim to less acidic deep mucosa
ureas: urea – ammonia (inc. mucous pH)
adhesins: bind surface of gastric epithelial cells
Gastric disorders: H. pylori uses urease to form ammonia which raises the pH, buffering the gastric tissue. The resulting host immune response (inflammation; gastritis) leads to injury. The bacterial enzymes also contribute to mucosal injury.
Finally, H. pylor stimulate the G-cells. How does this contribute to injury?
- stimulate G cells in antrum
- -infections predominate in antrum
- -inc. gastrin release - gastrin stimulates parietal cells to secrete HCl
- excess acid load injures duodenal mucosa (forming ulcers)
Gastric disorders: There are 2 virulence factos present in some strains of H. pylori that are believed to contribute to inc. risk of complications (e.g. gastric carcinoma).
- Cytotoxin-associated gene A (CagA)
- Vacuolating cytotoxin A (Vac A)
Describe these virulence factors
- CagA
- -organisms injects into host cell
- -interferes with cell processes (prolif. and diff. ) - VacA
- -secreted by organism
- -interferes w/ cell pathways (inc. inflammation, intracell. vacuoles)
Gastric disorders: True/False - In most patients, infection is limited to the antrum (inc. gastrin secretion and HCl production which increases duodenal ulcers).
However, in others, the entire stomach (pangastritis) may be involved. Over time, this results in destruction of gastric glands (gastric atrophy) which leads to hypochlorhydria (loss of parietal cells) and intestinal metaplasia.
True
*Gastric ulcers and carcinoma are associated with pangastritis pattern of infection
Gastric disorders: H. pylori si present in nearly all patients with duodenal ulcers and most with gastric ulcers/chronic gastritis.
Treatment of H. pylori requires multiple drugs and confirmation of cure. Explain
- Confirmation
- -stool antigen test
* if negative after 8 wks therapy, infection cured) - Treatment
- -amox + clinda + PPI
Gastric disorders: The choice of test used to Dx H. pylori depends on whether the patient requires an upper endoscopy.
Serologic detection of IgG abs is not often performed due to concerns over accuracy. Also, it does not distinguish b/t active and past infection. List tests used for H. pylori.
- Biopsy for Histology
- Biopsy urease test
- -alkaline pH and color change if + - Urea breath test
- -hydrolysis of urea by H. pylori – CO2 and NH3
- -(+) = CO2 detected in breath samples - Stool antigen test
- -(+) bacterial antigen = ongoing infection
- -use to establish initial Dx and confirm eradication
Motility drugs: Prokinetic drugs act to stimulate cholinergic neurons (and SM) thereby increasing contraction and propulsion.
There are 5 types/mechanisms:
- M3 agonists
- Ach inhibitors
- Dopamine (D2) agonists
- Motilin antagonists
- Serotonin ….
List examples of each.
- M3
- -Bethenecal - Ach inhibitor
- -Neostigmine - D2
- -metoclopramide
- -I.V.
- -excreted unchanged by kidney - Motilin agonist
- -erythromycin
Motility drugs: The clinical uses for prokinetic drugs are to increase gastric tone and constrict sphincters/SM.
What are the adverse effects/contraindications associate with prokinetic drugs?
Administration:
- -oral
- -Metoclopromide: IV
Metabolism:
–hepatic (except metaclopromide)
Adverse:
- cholinergic: parasympathomimetic
- Dopamin: EPS/hyperprolactinemia
Motlity drugs: Laxatives are drugs that are designed NOT to leave the intestine. They help to increase movement of fecal material. The following are the different kinds:
- Emollient (mineral oil)
- Saline (milk of Mg)
- Castor oil
- Psyllium (bulk forming)
- Natural compounds (Senna, Frangula, Aloe, Rhubarb)
List their features
- Emollient
- -non-absorbed
- -lubricates bowel - Saline
- -inorganic salt
- -inc. H2O into intestine (osmosis)
* *fast, but explosive!! - Castor oil
- -opens Cl- channels
- -H20/electyolytes into intestine - Psyllium
- -non-absorbable
- -forms hydrophilic mass (dec. transit time; inc. H2O)
* *safest, preferred - Natural
- -contain antrhraquinone glycosides
- -move H2o/electros into intestine; inc. fluid volume
Motility drugs: What are the adverse effects of laxatives?
- Secretory/stimulant agents
- Saline
- Mineral oil
- Secretory
- -electrolyte imbalance - Saline
- -Mg absorption
- -rectal epithelial sloughing - Mineral oil
- -dec. absorption of fat-soluble vitamins
- *pulmonary aspiration
Motility drugs: Anti-diarrheal drugs are effective for “non-specific” diarrhea that is NOT attributed to bacterial infection. They are most effective for management of acute diarrhea.
The following are classes of anti-diarrheals:
- opiates
- anti-secretory agents
- anti-cholinergics
- gel-forming
- ion exchanges resins
List examples of each and their functions.
NOTE: Most anti-diarrheal drugs act in the intestines (thus pharmacokinetics is not a factor.
- opiates
- -inc. flow resistance; dec. propulsion
ex: loperamide (piperadine); diphenoxylate/atropine (phenylpiperadine) - anti-secretory
- -dec. net fluid
ex: bismuth salicylate - anti-cholinergics
- -reduce contractile activity
ex: dicyclomine - gel forming
- -inc. flow resistance; inc. formed stools
ex: hydrated silum silicate, pectin, kaolin - ion exchange resins
- -bind bile water and salts
ex: cholesteryramine
Motility drugs: Opiate Anti-diarrheal agents (loperamide and Diphnoxylate) are given orally and are systemically-acting.
Descirbe absorption and metabolism of these agents
Absorption:
- Loperamide: poor
- Diphenoxylate: 90%
Metabolism:
- Loperamide: primarily biliary
- Diphenoxylate: hepatic
Motlity drugs: Side effects of opiates Loperamide and Diphenoxylate is based on their abilities to diffuse across the Blood Brain Barrier.
Loperamide has minimal diffusion, and low abuse potential. What amount that does enter the brain is pumped out by P-gp. How does this compare to diphenoxylate?
–sufficient diffusion
Side effects:
- -Euphoria (atropine added to reduce abuse)
- -Respiratory depression (high doses) - naloxone reverses
- -if metabolized difenoxin (active metabolite - 200x more potent)
Motility drugs: General points to treat poisoning include:
- maintain vital functions
- prevent further exposure
- combat toxic effects
- induce emesis
Syrup of Ipecac is an OTC emesis-inducing drug that can be used. It can cause local irritation and central CTZ stimulation. What are its contraindications?
- Corrosive acid or base = may aspirate
- CNS stimulants - inc. seizures
- Hydrocarbon = aspiration and chemical pneumonitis
- Activated charcoal = Ipecac (bind charcoal and neutralize both compounds)
Motlity drugs: Ondansetron and Granisetron are anti-emetic drugs that act as _____ antagonists that are used to treat chemotherapy-induced emesis. Odensetron is also used for post-operative emesis.
They help to relieve nausea and vomiting due to anti-neoplastic therapy, and can be given by I.V. (1st pass).
5-HT3 antagonists
-P450 metabolism
Adverse:
–few (some anaphylactic w/ odensetron)
Motility drugs: Metoclopramide and prochlorperazine are D2 Antagonists (anti-emetics) that are used in chemotherapy-induced emesis.
Their uses have declined with the development of 5HT3 antagonists, but are still used for less severe emesis. What are their side effects?
EPS and hyperprolactinemia
Motility drugs: Other anti-emetics include
- Dronabinol
- Dimenhydrinate
- Scopolamine
_____ is a chemotherapy-oinduced emesis when other drugs have failed. It has also been approved as an appetite stimulant in AIDS.
Dronabinol
Motility drugs: Other anti-emetics include
- Dronabinol
- Dimenhydrinate and meclizine
- Scopolamine
____ are H1 antagonists used for motion sickness
Demenhydrinate (dramamine) and meclizine (bonine)
Motility drugs: Other anti-emetics include
- Dronabinol
- Dimenhydrinate
- Scopolamine
Is an atropine-like muscarinic antagonist used to treat motion sickness
Scopolamine
Gastric disorders: NSAIDS impair mucosal defense mechanisms by inhibiting cycloxegenase and thus decreasing prostaglandin production.
True/False - Decreased prostaglandin leads to direct mucosal injury due to decreased mucin and HCO3- secretion as well as decreased epithelial regeneration.
True
Gastric disorders: Other factors that can lead to gastric injury include:
a. cigarette smoke
b. genetic predisoposition
c. blood group O
all of the above
- cigarettes
- -inc. PUD in smokers
- -dec. healing rate (inc. free radicals and dec. duodenal HCO3-) - Genetic
- -1st degree relative inc. risk (similar env. exposure) - Blood group O
- -enhance binding of H. pylor
Gastric disorders: H. pylor begins and often remains in the antrum. Over many years, the inflammation may extend and involve the more proximal stomach.
The associated injjury can cause patchy, atrophy (multi-focal atrophic gastritis) and lead to increased risk of metaplasia. It also lead to increased risk of malignant transformation to ________
adenocarcinoma
Gastric disorders: Long standing H. pylori infection can spread to the fundus/body of the stomach (from the antrum) and cause autoimmune gastritis. This occurs by diffuse T-cell mediated destruction.
It leads to loss of ______cells, which results in achlorhydria (hypergastrinemia) and loss of IF (pernicious anemia).
loss of parietal cells
*Dx using antibodies to parietal cells and IF
not directly responsible for injury, but Dx
Gastric disorders: Autoimmune T-cell mediated destruction of parietal cells due to long-standing H. pylori infection of the fundus and body (stomach).
Autoantibodies form against the parietal cell antigens and intrinsic factor. These autoabs are not pathogenic themselves, but are useful diagnostically.
Autoimmune gastritis
Complications:
- destroy parietal cells
- -loss of gastric acid
- -inc. gastrin (negative feedback) = G-cell hyperplasia and inc. risk carcinoid tumors
- -loss of IF = impaired B12 absorption = pernicious anemia - Long standing injury = intestinal metaplasia = adenocarcinoma
Gastric disorders: A gastrin-secreting neuroendocrine tumor (gastrinoma) that is usually located in the duodenum or pancreas.
It increases gastrin secretion (inc. acid production). It is sporadic and often malignant.
Zollinger Ellison syndrome
Gastric disorders: When should you suspect Zollinger ELlison?
a. multiple ulcers
b. ulcer resistant to therapy
c. family Hx of parathyroid or pituitary tumors
d. PUD + diarrhea (common)
all of the above
- Single ulcers in unusual locations (prox. duodenum)
- Multiple ulcers: distal duodenum or jejunum
- Ulcers resistant to therapy
- PUD + diarrhea
- Family Hx or parathyroid or pituitary tumors
- PUD without H. pylor or Hx of NSAIDS
Gastric disorders: In patients with Zollinger Ellison syndrome, PUD may be multiple and more distal than the typical locations.
Alongside PUD, what other clinical associations may be found?
- GERD
- malabsorption
- -inc. acid load in duodenum (inactivates pancreatic enzymes) - Liver = common site for metastasis from gastrinoma
*diarrhea, steatorrhea, weight loss
Gastric disorders: Serum gastrin is used to diagnose Zollinger Ellison. Normal serum gastrin is <150 pg/ml.
- Serum gastrin > 150: must measure gastric pH ratio to hyperchlorhydria. pH < 3 implies ______
- If serum gastrin is equivocal (150-1000) do secretin stimulation test. Elevated levels of gastrin indicate ___.
- Serum gastrin >1000 is diagnostic of _______.
- hyperchlorhydria
- -MC cause of elevated gastrin - possible gastrinoma
- diagnostic of gastrinoma
- must take patients off H2 blockers and PPI’s to Dx
- Secretin test: Patients fast overnight – bolus of secretin next morning (IV) – measure gastrin
Gastric disorders: A 45 year old male presents to the clinic compllaining of diarrhea and weight loss. You note ascites on PE.
Lab findings:
- enlarged gastric rugae (cerebriform)
- diffuse foveolar hyperplasia
What do you suspect?
Menetrier disease (hypertrophic gastropathy)
Gastric disorders: Menetrier disease presents with weight loss, peripheral edema, and diarrhea.
It is due to excessive secretion of transforming growth factor A. Explain the MOA
- Inc. TGFa
- Overstimulate EGFR
- mucous cells proliferate = fobeolar hyperplasia/excess mucous
- loss of protein
- –due to hypersecretion of gastric mucous - Edema
**possible increased risk for gastric cancer
Gastric disorders: Gastric polyps include
- ________: benign polyps that occur w/ gastritis, adjacent to ulcers and erosions.
- _______: sporadic polyps that are commonly produced from proton pump inhibitors (omeprazole). Inhibiting acid production – hypergastrinemia and stimulation of fundic glands.
- _______: Dysplastic with potential for malignant transformation (especially w/ increased size > 2cm). Increased incidence in familial adenomatous polyposis.
- Hyperplastic polyp
- Fundic gland polyp
- -familial adenomatous polyposis - Gastric adenoma
Gastric disorders: A benign SM tumor that most often occurs in the stomach.
It may ulcerate or bleed, but has NO malignant potential
Leiomyoma
MC benign soft tissue tumor in the stomach
Gastric disorders: Most gastric malignancies are gastric adenocarcinoma.
Risk factors include:
a. H. pylor
b. autoimmune gastritis
c. blood group A
d. high intake of salt-preserved foods and smoked meats
all of the above
*familial pre-disposition (hereditary diffuse gastric cancer - CDH1 gene mut.)
NOTE: dec. incidence in U.S. due to refrigeration
Gastric disorders: The “Intestinal” type of gastric adenocarcinoma is decreasing in incidence (due to dec. prevalence of H. pylori and dec. ingestion of dietary carcinogens due to refrigeration).
It is causally related to H. pylor in that, over time, inflammatory infiltrate leads to loss of original gastric glands (atrophic gastritis). Thus multi-focal atrophy may be followed by intestinal metaplasia. What does this lead to?
Hyperchlorhydria
—atrophic and metaplastic glands replace original glands and inc. acid production
*unstable epithelium = inc. risk dysplasia and malignancy
Gastric disorders: A patient you know has gastric adenocarcinoma.
This type arises from intestinal metaplasa, forms an exophytic mass, and resembles intestinal cancer (forms glands).
Intestinal type
Gastric disorders: This type of gastric adenocarcinoma is NOT associated with H. pylori. It is associated with diffuse thickining of the gastric wall (w/ no distinct mass).
On histology, you note diffuse infiltration of the wall and “signet ring” cells.
Diffuse type
- signet ring = mucin vacuole that displaces nucleus to the side
- pathogenesis: inactivation of CDH1 (encodes cadherin) = inc. tumor growth and invasion
Gastric disorders: The diffuse type of gastric adenocarcinoma is caused by loss of CDH1 gene that encodes E-cadherin.
E-cadherin is a cell surface protein that is involved with intercellular connections. Loss of this protein leads to loss of adhesion molecules and permits growth and invasion of tumor cells. What are clinical features of the diffuse type?
- high incidence of metastasis
- rapid disease progression
- poor prognosis
Gastric disorders: Weight loss and abdominal pain are the MC symptoms of gastric cancer at diagnosis.
Dysphagia is common in those with tumors arising in the _________.
Patients may also present with signs/symptoms of distant metastasis in the liver, peritoneal surfaces, and lymph nodes
dysphagia: proximal stomach and esophagogastric jxn
Gastric disorders: True/Fase - Common metastasis sites of gastric adenocarcinoma include
- Virchow node (left supraclavicular)
- Periumbilical subcutaneous tissue (Sister Mary Joseph nodule)
- Bilateral ovaries (Krukenberg tumor; signet ring type)
True
Gastric disorders: Velvety dark plaques on the axilla, and posterior neck. They are commonly associated with gastric adenocarcinoma.
Acanthosis nigrans
*not specific for malignancy, but if malignancy is present, it is MC gastric cancer
Gastric disorders: True/Fasle - Multiple seborrheic keratosis (sign of Leser trelat) is a paraneoplastic manifestation associated with gastric adenocarcinoma
True
Gastric disorders: Treatment of gastric adenocarcinoma involves surgical resection.
Prognosis depends on stage (depth of invasion, extend of nodal and/or distant metastasis).
True/False - stage of tumor increases with increasing depth of invasion into the gastric wall
true
Gastric disorders: Gastric lymphoma is the MC extranodal site of lymphoma. Most are extranodal marginal zone B-cell lymphoma (MALToma). However, less commonly, we see diffuse large B cell lymphoma.
MALToma is a type of low grade B cell lymhoma that is related to chronic stimulation of MALT by ______.
H. pylori
- Tx infection = lymphoma resolves
- non-specific clinical features
Histo: dense, lymphocytic infiltrate w/ lymphoepithelial lesions
IBS drugs: _______ can be used to Tx traveller’s diarrhea. It is similar to rifamycin. Little absorption, so most of the drug remains in the intestine (site of action
Rifaximin (XIFAXAN)
IBS drugs: Drugs to treat inflammatory bowel include:
- Aminosalicylates (5-ASA)
- Steroids (Glucocorticoids; anti-inflammatory)
- Immune modifiers (Azathioprine, 6-MP, methotrexate)
- Biologic therapy (Infliximab)
- Antibiotics (metronidazole, ampicillin, cipro)
- Non-drug treatment therapy (surgery; MC Crohn’s)
How do you treat an IBS patient with unknown causes?
Tx symptoms
- dietary changes, stress manamegment
- pharm varies patient to patient – can be difficult
IBS: The current (standard) approach is to treat “bottom up” according to severity of the illness. The bottom up approach involves:
- mild: antibiotics, salicylates
- moderate: immunomods and corticosterods
- biologics
Hows does this compare with the newer “top down” approach?
Treat early to late stages
- Early
- -immunomodulators/biologics - Middle
- -immunomods + corticosteroids + aminosalicylates - Late
- -immunomods
- -surgery or antibiotics or aminosalicylates
IBS: Aminosalicylates include: Sulfasalazine (5 ASA), Olsalazine balsalazine (and forms of mesalamine). These drugs form AZO bonds with other molecules to prevent absorption of the 5 ASA parent compound in the small intestine, thus allowing the drug to enter the large intestine and enabling remission in UC.
True
- Sulfasalazine
- -Sulfapyridine linked to 5 ASA (mesalamine) by AZO bond
- -sulfapyridine (rapid absorption in colon - no therapy) - Balsalazide
- -5 ASA + 4 aminobensoyl-B alanine - Olsalazine (diaminosalicylate)
- -2 5 ASA molecules together
- -broken down by intestinal bactera to form 2 5-ASA’s
IBS: What is the Mechanisms of action of Salicylates (sulfsalazine, olsalazine)?
a. inhibit prostaglandin synthesis via inhibition of COX-1
b. inhibit cell function of NK cells, lymphocytes and macrophages
c. scavenge free radicals and prevent oxidative damage
d. inhibit NF-KB
All
- inhibit COX (PG biosynthesis),
- -tf for pro-inflamma cytokines
- -inhibit IL-1 and TNF-a
- -inhibit NFK-B
- -inhibit cell fxn of NK cells, lymphocytes, macros
- -scavenge free radicals/prevent ox damage
IBS: Mesalamine (5ASA) is the active metabolite of salycilates. Mesalamine-only formulations include:
- Pentasa
- Asacol
- Enema or Suppository
How do they work?
- Pentase
- -time release micro-granules (throughout SI) - Asacol
- -coated 5 ASA
- -dissolves at pH 7 (ileum and colon) - Enema
- -5 ASA may be delivered in high conc. (sigmoid colon)
IBS: Salicylates are used to maintain remission in UC. Efficacy is unknown in Crohn’s disease (more efficacious in UC). Efficacy in Crohn’s is dependent upon the site of inflammation (SI vs. LI) and confined to use of the suppository.
If the disease extends to the proximal colon (UC or Crohn’s) what formulations can be used?
AZO and meslamine
IBS: What are the side effects of salicylates?
- Sulfasalazine (releases sulfapyridine)
- -nasua, bone marrow suppression, GI uupset
- -ulfonamides – hemalytic anemia or hepatitis - Osalazine
- -secretory diarrhea - Mesalamine (high doses)
- -interstitial nephritis
IBS: Glucocorticoids act to:
- inhibit formation of inflammatory cytokine (TNF alpha, IL-1) and chemokine (IL-8)
- reduce the expression of inflammatory cell adhesion molecules,
- inhibit gene transcription of NO synthase, phospholipase A2, COX-2, NF-Kb
They are NOT useful at maintaining remission. What are their clinical uses?
- Prednisone/Prednisolone
- -intermediate
- -orally - Hydrocortisone
- -fast acting steroid
- -enema, foam suppository
- -minimize systemic glucocorticoid effect - Budesonide
- -time release (distal ileum/colon)
- -Tx moderate to severe inflammatory bowel
IBD: What are the side effects of glucocorticoids with respect to:
- bone
- gut
- glucose
- CNS
- Inc. bone absorption
- -alter Ca2+ handling
* *children; post-menopause - Inc. peptic ulcer
- -inc. acid production
- -dec. mucopolysaccharides - Hyperglycemia (DM)
- -a. inc. gluconeogenesis and secretion by liver; sensitivity to glucagon; substrate for gluconeogenesis
- -b. dec. glucose uptake by peripheral tissues - Inc. arousal and euphoria
- -prolonged = depression/sleep issues/psychosis
IBD: Purine analogs include purine anti-metabolites (Azathiopurine and 6-mercaptopurine).
They are immunosuppressive drugs that are believed to act by enhancing apoptosis of T-lymphocytes and inhibiting cell division and proliferation (by inhibiting nucleotide metabolism).
Describe these drugs
- Azathopurine
- -bioavailability better than mercaap.
- -converted non-enzymatically to 6-MP - 6MP
- -metabolized by xanthine oxidase and thiopurine methyltransferase to: thioguanine or inactive metabs.
* *long half life (delays azathoprine effect to 17 weeks)
IBD: Purine analogs are used for induction and maintenance of remission (UC and Crohn’s after 3-6 mos Tx). They maintain remission in ~80% of patients.
When administered for long durations, steroid doses must be reduced. What are their adverse effects?
- nausea, vomiting bone marrow suppression
- -leukopenia, anemia thrombocytopenia
- -leukopenia responds to dose reduction or GSF
* must monitor Thioguanine levels (TMT defciency inc. bone marrow suppression) - Hypersensitivity reactions
- -pancreatitis, hepatitis, fever
IBD: Purine analogs can have drug interactions with Allopurinol.
Allopurinol reduces the activity of xanthine oxidase, decreasing the metabolism of purine analogs. What is the net result?
High thioguanine = leukopenia
Fix by reducing dose of azathioprine (when taking allopurinol)
*~50% of normal dose
IBD: Methotrexate is an anti-metabolite used to treat chronic inflammatory diseases (Crohn’s, RA, Cancer).
It inhibits dihydrofolate reductase (DHF reductase) which is essential for synthesis of thymidine and purines.
How is it used clinically?
- Cancer - high doses
- -inhibit cell prolifer. - Interferes with inflammation
- -via IL-1 - Stimulates relase of adenosine
- -anti-inflamm - may induce death of T-cells
IBD: Methotrexate is used to induce and maintain remission in Crohn’s. It’s efficacy in UC is unknown.
What are adverse effects associated with methotrexate?
- Low incidence:
- -bone marrow suppression, alopecia, mucositis, megaloblastic anemia
*uncommon
IF side effects occur - reduce dose and give folic acid
Biochem: A kid who presents with decreased eye contact, exaggerated startle response, hyperreflexia and maculae with a cherry red spot.
Labs reveal onion skin lysosomes (labs)
most likely has a deficiency in
B hexosaminidase
*Tay sachs (accumulate G2 ganglioside)
- -**regression of achieved milestones
- -neurodegeneration (macroencephaly, difficulty moving), developmental delay,
Biochem: A kid who presents with recurrent pneumonia, hepatosplenomegaly, cherry red maculae.
Foam cells prsent in bone marrow, spleen and liver. Zebra bodies (myelinated membranes (parallel palisading laminae)
Niemann Pick
*sphingomyelin accumulation (def. sphingomyelinase)
Biochem: A patient presents with glomerulonephritis, hematuria and sensorineural hearing loss.
Ocular findings include anterior lenticonus.
Labs reveal:
- Microhematuria
- Splitting of the glomerular BM (basketweave) on biopsy
*can’t pee, can’t see, can’t hear a bee
Alport Syndrome
- Mutation in type IV collagen
- end stage renal disease
Biochem: A kid who presents with osteoporosis, pancytopenia, bone crises, avascular necrosis and hepatosplenomegaly.
Labs reveal lipid-laden macrophages that look like tissue paper
Gaucher disease
def. B-glucocerebroside
* glucocerebroside accumulation
* Gaucher cells
Tx: recombinant glucocerebroside
Biochem: A patient who presents with black pigmented tissues
Alkaptonuria
*dec. B-homogentisate oxidase
Pixorize: “Owl captain” uria
Biochem: A patient who presents with a protuberant abdomen, puffy cheeks, rounded face…
Labs reveal severe hypoglycemia, lactic acidosis and hyperuricemia (gout).
Von Gierke
*dec. gluc 6-phos translocase
Biochem: A patient presents with developmental delay, delayed language development, long facies, large ears, macrochordism (testicular enlargement) and mitral valve prolapse.
Joints are hypermobile and pes planus.
Fragile X
- X-linked dominant
- trinucleotide repeat FMR1 gene
- inc. methylation
Biochem: A patient presents with maple syrup/burnt sugar smelling urine
Maple syrup urine disease
*Leucin
Biochem: patient presents with almond shaped eyes, turned down mouth, and increased appetite
15q11q13
*mutation of paternal (microdeletion)
Biochem: Patient presents with thin upper lip, receding chin and smooth philtrum
fetal alcohol syndrome
Biochem: Patient presents with hypotonia, abnormal facial grimacing, hepatomegaly
Zellweger syndrome
*absence of peroxisomes
Biochem: A child (6-18 mos) presents with regression of motor skills, speech and cognition.
On PE you note vocal grunting and hand wringing
a. Rett
b. Krabbe
c. Puetz Jegher
d. Williams
Rett syndrome
- X-linked dominant
- microdeletion of methyl CPG binding protein 2
- progressive loss of intelligence, cognition (language, motor)
- females
Biochem: A patient presents with neuropathies, limb stiffness and optic atrophy
Lab reveals globoid cells
Krabbe disease
*def. galactocerebrosidase
Biochem: A patient present with angiokeratomas, burning pains in his hands and feet and foamy urine
a. Fabry
b. Rett
c. Cri-du Chat
d. Gaucher
Fabry
X-linked recessive
*def. a-galactosidase A
