Digestion and Metabolism Flashcards
Cells that secrete gastric acid
parietal cells
Cells that secrete intrinsic factor. What is the role of intrinsic factor?
Parietal cells.
Intrinsic factor allows for the absorption of vitamin B12 (cobalamin) by the ielum. Pernicious anemia (type II hypersensitivity) production of autoantibodies that dec intrinsic factor
Gastrin
Released by G cells of the stomach antrum
Increases H+ secretion, inc growth of gastric mucosa, inc gastric motility
What causes gallbladder contraction?
Release of CCK by I cells of the duodenum – allows for secretion of bile into the duodenum
Stimulated by fatty foods
What increases secretion of pancreatic HCO3-?
Secretin: released by S cells of the duodenum in response to acidic chyme
Allows for functioning of pancreatic enzymes
Chief cells of the stomach
Release pepsinogen
Pepsinogen –> pepsin in acidic environment
What activates trypsinogen (into trypsin)? What happens if there is a deficiency in this?
Enterokinase/enteropeptidase (from intestinal cells)?
Deficiency leads to malabsorption and steatorrhea
Deficiency in which pancreatic enzyme will cause steatorrhea?
Pancreatic lipase
Pancreatic lipase is normally inhibited by bile acids, but colipase helps overcome this – anchors lipase to triacylglycerol and stabilizes the active conformation
Kupffer cells
specialized macrophages of the liver that form the lining of sinusoids
Lab values in alcoholic hepatitis
AST>ALT
make a toAST with alcohol
Lab values in nonalcoholic hepatitis
ALT>AST
Patient presents with cirrhosis, diabetes mellitus, and skin pigmentation
Hemochromatosis
Iron overload leading to deposition in organs (AR mutation in HFE gene)
What can hemochromatosis do to the heart?
Reversible dialted cardiomypathy
Histology of the liver shows finely granular inclusions that are pale and eosinophilic
Characteristic of Hep B infection
Histology of the liver shows lymphoid aggregates within the portal tracts and focal areas of macrovesicular steatosis
Characteristic of Hep C infection
Meckel diverticulum
Partial closure of the vitelline duct, with the patent portion attached to the ileum – may be asymptomatic or present with rectal bleeding or obstruction
Ingestion of wild toxic mushrooms has what effect?
Binds to and inhibits RNA pol II – halts mRNA synthesis, resulting in apoptosis
What are people with Celiac disease intolerant to?
Gliadin (a component of gluten)
What are the lab findings in a patient with Celiac disease?
IgA anti-tissue transglutaminase, anti endomysial, and anti-deamidated gliadin peptide antibodies
What parts of the small intestine are affected by Celiac disease? What does histology show?
Distal duodenum and/or proximal jejunum
Will see villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis
VIP (Vasoactive intestinal polypeptide)
Secreted by the pancreas
Causes increased water and electrolyte secretion
Patient presents with watery diarrhea, hypokalemia, and achlorhydria (no HCl in gastric secretions)
WDHA syndrome = VIPoma
A pancreatic islet cell tumor that secretes VIP
1 g protein = ? calories
1 g carbs = ? calories
1 g fat = ? calories
1 g protein = 4 calories
1 g carbs = 4 calories
1 g fat = 9 calories
Hirschsprung disease
congenital megacolon caused by absence of ganglion cells in the colonic wall – affected area is narrowed and there is compensatory dilation of proximal areas
Due to failure of neural crest cell migration
Mutation in Lynch syndrome leading to colorectal carcinoma?
What else is this associated with?
Mutation of DNA mismatch repair genes (MSH2 and MLH1)
Also associated with ovarian, endometrial, and skin cancers
Where are dietary lipids absorbed?
Jejunum
Risk factors for gallbladder disease
Four F’s
Fat
Female
Forty
Fertile (pregnant)
What do brown gallstones suggest?
Infection
Patient presents with fever, jaundice, and RUQ pain
Charcot’s triad – cholangitis
Wilson disease
An AR mutation that results in impaired cellular transport of copper – causes copper accumulation in the liver, brain, and eye
Present with hepatitis, depression, impulsivity, basal ganglia injury (ataxia, parkinsonism, tremor), Kayser Fleischer rings seen on ophthalmalogic exam
What happens if you give Aspirin to a child with a viral infection?
Reye syndrome: mitochondrial dysfunction (decrease in B oxidation by reversible inhibition of mitochondrial enzymes) leading to hepatic encephalopathy –> death
Direct hernia
Medial to inferior epigastric
Tears through abdominal fascia and passes through the superficial inguinal ring
Most common in adult men
Indirect hernia
Lateral to inferior epigastric
Passes through deep inguinal ring and superficial inguinal ring –> scrotum
Covered by all three layers of spermatic fascia
Most common in male infants – Due to failure of processus vaginalis to close (can lead to hydrocele formation)
Femoral hernia
Protrudes below the inguinal ligament and lateral to the pubic tubercle – enters the femoral ring (where the lymphatics run through)
Most common in females
What bug causes chronic otitis media in diabetics
Pseudomonas
Round, pearly mass behind the TM in the middle ear (abnormal finding)
Cholesteatoma: collection of squamous cell debris
What lies within the hepatoduodenal ligament?
The portal triad: hepatic artery, portal vein, and common bile duct
Plummer Vinson Syndrome
Dysphagia
Iron deficiency anemia (microcytic)
Esophageal webs
Boerhaave Syndrome
Transmural rupture of the esophagus due to violent retching
Seen in bulimia
Punched out ulcers in esophagus
HSV1 infection
Linear ulcers in esophagus
CMV infection
White pseudomembrane covering esophagus
Candidiasis
Where is iron absorbed?
Duodenum
Where is folate absorbed?
Jejunum
Where is cobalamin (B12) absorbed?
Ileum
Needs intrinsic factor (from parietal cells)
Fates of short, medium, and long chain fatty acids?
Short and medium chain FFA are absorbed by enterocytes and pass directly into capillaries without modification –> Reach liver directly via portal blood
Long chain FFA enter the enterocytes and are made into chylomicrons which enter lymphatics –> capillaries
fat soluble vitamins
A, D, E, K
Role of apoE in chylomicrons
Allows for uptake of chylomicron remnants by the liver
Role of apoCII in chylomicrons
Activates lipoprotein lipase (found on vascular endothelium by non hepatic tissues) which allows for the release of FFA from chylomicrons
What do nascent chylomicrons have on them?
apoB48
they become mature chylomicrons by acquiring apoE and apoCII from HDL
Absorption of:
glucose
galactose
fructose
Glucose and galactose are absorbed by SGLT1 (Na dependent)
Fructose is absorbed by GLUT-5
Treatment of portal HTN
Transjugular intrahepatic portosystemic shunt (TIPS) between the portal vein and hepatic vein shunts blood to the systemic circulation and bypasses the liver
Enzyme in cholesterol stone formation
due to reduced 7a hydroxylase activity (decreased bile acid production and increased excretion of cholesterol → stones)
Enzyme in pigmented stone formation
Beta glucuronidase – after infection, beta glucuronidase released by injured hepatocytes and bacteria hydrolyzes bilirubin glucronides to unconjugated bilirubin
Medical management of cholesterol stones
administration of hydrophilic bile acids to reduce biliary cholesterol secretion and increase biliary bile acid concentration – promotes gallstone dissolution by improving cholesterol solubility
Patient with a known history of liver disease prevents with a hand flapping tremor. What has accumulated and what has decreased in this patient?
Excess NH3 causes a depletion of a-ketoglutarate, which leads to inhibition of the TCA cycle
(The liver disease makes the pt unable to metabolize waste products)
Which hereditary hyperbilirubinemia is most severe and leads to death within a few years of life?
Crigler-Najjar syndrome: absent UDP-glucuronosyltransferase (liver is unable to conjugate bilirubin)
Patient presents with conjugated hyperbilirubinemia and a grossly black liver
Dubin Johnson syndrome: unable to excrete conjugated bilirubin from the liver
4 year old child presents with numerous hamartomatous polyps in the GI tract
Juvenile polyposis syndrome
AD
Associated with inc risk of colorectal carcinoma
Teenager presents with hyperpigmented oral mucosa and lips, and has numerous hamartomas throughout the GI tract
Peutz-Jeghers syndrome
AD
Inc risk of breast and GI cancers at a young age
Your patient hits puberty and develops thousands of colonic polyps that also involve the rectum. What is the mutation and what is the treatment?
Familial adenomatous polyposis
AD mutation of APC tumor suppressor gene on chromosome 5 (5 letters in “polyp”)
Prophylactic colectomy or else 100% progress to colorectal carcinoma
Inc alpha fetoprotein
HCC
Positive anti-mitochondrial antibodies
Primary biliary cirrhosis
Positive anti-smooth muscle antibodies
Primary sclerosing cholangitis
Why are some babies yellow when they are born? what is the treatment?
They have an immature UDP-glucuronosyltransferase enzyme so there is a buildup of unconjugated bilirubin
Phototherapy isomerizes unconjugated bilirubin to water soluble form
In patients with a1 antitrypsin deficiency, where does the misfolded protein aggregate?
In the ER of hepatocytes –> leads to cirrhosis
What causes hemochromatosis?
Mutation in HFE- causes increased intestinal absorption of iron leading to iron overload
Immune cells involved in Crohn vs Ulcerative Colitis
Crohn: Th1
Ulcerative colitis: Th2
Patient injured her knee and was given a medication for the pain. She soon developed colicky RUQ abdominal pain. What medication was she given that caused these symptoms?
Opioid (morphine)
Can cause contraction of the sphincter of Oddi – leading to inc common bile duct pressures and biliary colic
How does malabsorption contribute to gallstone formation? (eg Crohns disease)
Decreased absorption of bile acids (inc bile acid wasting) from the ileum means that there are less bile acids available for bile formation and the ratio of cholesterol to bile acids increases – causes cholesterol to precipitate and form stones
Esophageal cancer differences
Squamous cell: upper 2/3 – due to alcohol, smoking, and hot liquids
Adenocarcinoma: lower 1/3 – due to GERD, barrett esophagus, obesity
Effect of phosphatidylcholine on cholesterol and gallstones
Increase solubility of cholesterol and decrease the risk of gallstones
Noncaseating granulomas seen in colonoscopy of a patient with bloody diarrhea
Crohns disease
Histo shows microvesicular steatosis without inflammation in a recently sick child
Reye Syndrome - given ASA
Histamine effects on GI
Causes increased gastric acid release from parietal cells that can lead to gastric ulceration
The excess acid inactivated pancreatic and intestinal enzymes, leading to diarrhea
Ondansetron: mechanism and toxic effects
Anti emetic that blocks serotonin (5HT receptors and causes dec vagal stimulation)
Can cause constipation, headache, dizziness, long QT, and serotonin syndrome
Patient presents with several months of pain after eating which has caused him to decrease his food intake and has led to weight loss
Chronic Mesenteric Ischemia: atherosclerosis of the celiac a., SMA, or IMA that leads to intestinal hypoperfusion (GI angina)
Mallory Weiss Syndrome
Longitudinal mucosal tears at the gastroesophageal junction that occur due to rapid increase in intra-abdominal pressure, usually due to vomiting (seen in alcoholics and bulimia)
Retroperitoneal organs
SADPUCKER
- Suprarenal glands
- Aorta and IVC
- Duodenum (except 1st part)
- Pancreas (head and body)
- Ureters and bladder
- Colon (ascending and descending)
- Kidneys
- Esophagus
- Rectum
Sequelae of anterior vs posterior duodenal ulcers
Anterior: cause perforation
Posterior: cause hemorrhage (gastroduodenal artery)
Sudan III stain
Identifies unabsorbed fat and confirms malaborption
Colonoscopy shows Flask shaped ulcerative lesions
Entamoeba histolytica
Colonoscopy shows Spindle shaped tumor cells with small vessel proliferation
Kaposi’s sarcoma
Zollinger Ellison Syndrome
What is it associated with?
Gastrin secreting tumor of the pancreas or duodenum that causes ulcers in duodenum and jejunum
Associated with MEN1
Diagnosis of Zollinger Ellison Syndrome
Patient presents with diarrhea and abdominal pain
Positive secretin stimulation test: gastrin levels stay high after administration of secretin, which normally inhibits gastrin release
Treatment of carcinoid syndrome
Octreotide: synthetic analog of somatostatin
When does carcinoid syndrome occur?
When a carcinoid tumor of the GI tract metastasizes to the liver
Patient presents with flushing, watery diarrhea, and telangiectasias
Carcinoid syndrome: release of vasoactive substances (serotonin, bradykinin, and prostaglandins)
Neonate presents with drooling, choking, and vomiting with first feeding. XR shows gasless abdomen and the doctor is unable to pass NG tube into stomach
Tracheoesophageal abnormality
Aflatoxins
Produced by Aspergillus – cause a p53 mutation (classically G;C –> T;A) which can lead to hepatocellular carcinoma
Porcelain gallbladder
calcified gallbladder seen on imaging with a thickened gallbladder wall – need to perform prophylactic cholecystectomy because of high rates of gallbladder cancer
Progression of mutations in colon cancer
AK-53
APC
KRAS
p53
Treatment of hepatic encephalopathy
Lactulose – dec the pH of the intestinal lumen which then causes ammonia to be changed into ammonium, which is excreted
Rifaximin – a non absorbable antibiotic that kills the intestinal bacteria that produce ammonia
Elderly patient presents with oropharyngeal dysphagia, halitosis, regurgitation, and recurrent aspiration. What is this and what causes it?
Zenker diverticulum
Diminished relaxation of cricopharyngeal muscles during swallowing results in increased intraluminal pressure of the oropharynx –> causes a zone of muscle weakness in the posterior hypopharynx forming a false diverticulum.
Gallstone ileus
when a large gallstone causes formation of a cholecystenteric fistula between the gallbladder and adjoining gut → usually the duodenum. It then travels to the ileocecal valve, which is the narrowest portion of the intestine causing obstruction
Internal vs external anal sphincter
o Internal sphincter: involuntary, parasympathetic pelvic splanchnic nerves (relaxes in response to pressure – gas or feces- descending the rectal ampulla)
o External sphincter: voluntary, inferior rectal nerve
Mallory bodies
Intacytoplasmic eosinophilic inclusions of damaged keratin filaments
Seen in alcoholic hepatitis (AST>ALT)
Wilson disease vs Hemochromatosis
Mechanism:
Inheritance:
Parts affected:
Treatment:
Wilson disease:
- accumulation of copper due to impaired excretion
- autosomal recessive
- Liver, eyes, brain, kidney, joints
- chelation with penicillamine
Hemochromatosis:
- accumulation of iron due to inc intestinal absorption
- autosomal recessive
- liver, heart, joints, skin, pancreas
- repeated phlebotomy, chelation with deferasirox
What drugs should not be taken with antacids like calcium carbonate?
Tetracylines or Fluoroquinolones – can lead to chelation of the drug and decreased effectiveness
Bilious vs nonbilious vomiting in a neonate?
What causes these?
Nonbilious = pyloric stenosis
Due to exposure to macrolides
Bilious = intestinal atresia
Duodenal is a failure to recanalize
Jejunum/Ileum is due to vascular injury
Bilious = annular pancreas
Due to abnormal migration of the ventral pancreatic bud
What is the hepatic portal vein made up of?
The splenic vein and the superior mesenteric vein
*the inferior mesenteric vein joins either the splenic or the superior mesenteric vein or the junction of these two veins
Large intestine blood supply: Cecum Ascending colon Transverse colon Descending colon Sigmoid colon
Cecum = ileocolic artery (SMA)
Ascending colon = right colic artery (SMA)
Transverse colon = middle colic artery (SMA)
Descending colon = Left colic artery (IMA)
Sigmoid colon = sigmoid arteries (IMA)
Pancreatic tumors that arise in the head of the pancreas cause obstruction of what?
Common bile duct
Superior Mesenteric Artery Syndrome
What is this?
What is it associated with?
when the transverse duodenum is compressed between the SMA and aorta.
S/S: postprandial pain
Typically associated with conditions with diminished mesenteric fat (low body weight/malnutrition)
Arterial and nervous supply above vs below pectinate
Above:
- Superior rectal artery (IMA)
- Visceral innervation (no pain!)
Below:
- Inferior rectal artery (internal pudendal artery)
- Inferior rectal branch of pudendal nerve – (painful!!)
Where are peyers patches?
Ileum
Angiodysplasia
tortuous dilation of vessels → hematochezia
Most often found in cecum, terminal ileum, ascending colon
More common in older patients
Colorectal cancer presentation in ascending colon vs descending colon
Where is the most common area of colorectal cancer?
Rectosigmoid>ascending>descending
Ascending- exophytic mass, iron deficiency anemia, weight loss
Descending- infiltrating mass, partial obstruction, colicky pain, hematochezia
What can exposure to arsenic or vinyl chloride cause?
Angiosarcoma of the liver
Arsenic can also cause skin SCC
What zone of the liver does yellow fever affect?
Zone II
yellow = II
What zone of the liver does ingested toxins affect?
Zone I: periportal zone
What zone of the liver is affected first by ischemia?
Zone III: centrilobular zone
What zone of the liver contains cytochrome P450 system?
Zone III: centrilobular zone
What zone of the liver is damaged by ingested toxins?
Zone 1: periportal zone
What causes umbilical hernia and what is this associated with?
defect at the linea alba covered by skin – caused by incomplete closure of the umbilical ring, which allows protrusion of the bowel through the abdominal musculature
Associated with Down Syndrome and congenital hypothyroidism
Patient presents with abdominal pain and diarrhea for several weeks. He now has a skin lesion over the abdomen and bowel contents appear to be draining to the surface of the skin in the RLQ of the abdomen. What condition does he likely have?
Crohn Disease
Fistula formed between the bowel and the skin of the abdominal wall (enterocutaneous fistula)
What section of the GI system is always involved in Hirschsprung’s disease? Why?
Neural crest cells mmove caudally, so the rectum is ALWAYS involved
In hepatic encephalopathy, what accumulates in the astrocytes of the CNS?
Accumulation of glutamine in the CNS astrocytes: when excess ammonia is in the blood, it crosses the BBB and is taken up by astrocytes, increasing glutamine production → causes astrocyte swelling and impaired glutamine release.
Hyperammonemia consequently decreases the amount of glutamine available for conversion to glutamate in neurons, resulting in disruption of excitatory neurotransmission
Mechanism of chronic vs acute mesenteric ischemia?
Chronic: atherosclerosis
Acute: embolism
Histo of liver shows spotty necrosis with ballooning degeneration (haptocyte swelling), Councilman bodies (eosinophilic apoptotic hepatocytes), and mononuclear cell infiltrates
Hepatitis A
Abetalipoproteinemia
Impaired formation of apoB-containing lipoproteins (chylomicrons and VLDLs)
o Lipids absorbed by the small intestine cannot be transported into the blood and accumulate in the intestinal epithelium
o Histo: normal intestinal mucosal architecture but the enterocytes contain clear or foamy cytoplasm which is more prominent at the tips of the villi
o RBCs show acanthocytes (spur cells
How can Aspirin reduce risk of colon cancer?
Increased activity of COX2 has been found in many forms of colon adenocarcinoma and in inherited polyposis syndromes.
Pancreatic pseudocyst
Complication of acute pancreatitis
Lined by granulation tissue
Stomach wall is grossly thickened and leathery
Diffuse signet cell carcinoma of the stomach – Often infiltrate large areas of the stomach walls causing a “leather-bottle stomach” (linitis plastic)
consist of cells that do not form glands – cells often contain abundant mucin droplets that push the nucleus to one side and lead to the characteristic appearance of a signet ring
Metoclopramide
antagonizes D2 receptors in the area postrema to prevent chemotherapy induced vomiting
o Upper GI prokinetic effects: inc resting tone, contractility, LES tone, and motility – useful in treatment of delayed gastric emptying due to post surgical disorders and diabetic gastroparesis
o Due to D2 blockade, can cause extrapyramidal effects – dystonia, parkinsonian features, tardive dyskinesia
Lactase deficiency testing
Deficiency: stool will have dec pH and breath will have inc hydrogen content
Bacterial fermentation of lactose produces short chain fatty acids (acetate, butyrate, and propionate) which lower stool pH and produces hydrogen gas → flatulance
Acalculus cholecystitis
What is this?
Who is this most often seen in?
acute inflammation of the glallbladder in the absence of gallstones. – Thought to arise from gallbladder stasis and ischemia, which cause inflammation of and injury to the gallbladder wall
Most commonly occurs in critically ill patients (those with sepsis, severe, burns, trauma, immunosuppression) and is associated with high mortality
Patient presents with 2 year hx of abdominal discomfort, greasy stool and weight loss. He has also been experiencing joint pain. An intestinal biopsy reveals multiple macrophages loaded with PAS positive granules in the lamina propria. What is this and how should the patient be treated?
Whipple disease: infection with Tropheryma whipplei (intracellular gram positive) causes malabsorption, cardiac symptoms, arthralgias, and neurologic symptoms – treat with antibiotics
Proliferate only within macrophages – Foamy macrophages in intestinal lamina propria that are PAS positive (presence of glycoprotein) and contain the rod shaped bacilli
Decreased lipid transport across enterocyte – lymphatics become blocked with fat
What is the pathogenesis of Reye syndrome?
Mitochondrial dysfunction: Aspirin causes uncoupling of the electron transport chain
Most common causes of acute pancreatitis?
- Alcohol
- gallstones
- hypertriglyceridemia
