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186 Cards in this Set
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What 3 major glands produce saliva? Key features of each gland and general structure of the glands?
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Parotid, Submandibular, Sublingual.
Parotid: serous gland, active on stimulation, produces 25% of saliva Submandibular: mostly serous gland, active when unstimulated, produces 7% of saliva Sublingual: mostly mucous 5% of saliva production The salivary glands have an acinar end that produces fluid, ions, and amylase and a ductal system that modifies the fluid. |
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What are some of the functions of saliva? What controls the production and flow of saliva?
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Saliva is completely under control of the autonomic nervous system, no hormonal control. Parasympathetic stimulates secretion. Saliva moistens our mouth, helps digest food with amylase, acts as a buffer from acid, mineralizes enamel, is anti-bacterial.
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What happens to ions in saliva as it passes through the ducts?
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Ionic concentration is determined by the flow rate, and as flow rate increases, ion concentration also increases.
Potassium and bi-carb are in higher concentration than the plasma (they get secreted into the saliva), while Na and Cl are in lower concentration (they get reabsorbed). |
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What are the five tastes and key features of each type of taste?
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Sweet: mediated by G proteins, targets energy rich nutrients, level of sweetness dependent on temperature.
Bitter: mediated by G proteins, targets aversive foods or toxins, has the highest sensitivity of all the tastes. Sour: mediated by direct receptors, targets acids (H+) Salty: mediated by direct receptors, targets electrolyte balance with NaCl Umami: mediated by g proteins, targets amino acids |
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What are supertasters, tasters, and non-tasters?
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Different people have different reactions to taste depending on the density of receptors. Supertasters have a higher density of fungiform papillae, and are less likely to enjoy/eat certain foods because they are more sensitive to the taste.
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How does the taste receptor cell pathway function?
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Sour and salt modulate taste receptors by direct effects on ion channels, sweet/bitter/umami go through g protein signaling. In the gr protein signaling, there is a transduction cascade that leads to release of calcium and neurotransmitter release.
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What is the role of bi-carb in the GI tract? What exchangers are key?
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Bi-carb is important in preventing changes in pH, it acts as a buffer. Most of the GI tract is in the pH range of 6-8, which is needed to gastric enzymes to function. It also plays a role in bile acids and mucin solubility.
Bi-carb/chloride: pumps bicarb into lumen, chloride gets taken into cell. Major way bicarb gets secreted. CFTR: pumps chloride into lumen, when defective in CF the other bicarb exchanger loses function Bi-carb/sodium: pumps bicarb into cell from blood, co-transports sodium |
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How is intracellular pH maintained in the GI tract?
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Whatever ion is being secreted into the lumen of the GI tract, the opposite ion gets secreted into the blood on the basolateral side.
Stomach: H+ secreted into stomach, bi-carb pumped into blood Pancreas: Bi-carb secreted into lumen, H+ pumped into blood |
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What is sialadenitis? Common causes?
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Sialadenitis is the inflammation of the salivary glands. It can be traumatic, infectious, or automimmune.
Viral: Mumps, constitutional symptoms + painful swelling of parotid glands, testicles in males. Preventable by vaccine. If the sialadenitis is chronic, likely due to an inflammatory condition or a stone. |
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What is sialolithiasis? What are mucoceles?
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Salivary duct stones, due to debris or stasis of the ducts. May need surgery to remove.
Mucocele is a common swelling often found on the lower lip, usually due to trauma. Cystic space filled with mucin. Ranula if it sublingual. |
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What is Sjogren's Syndrome?
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An autoimmune disorder, characterized by the destruction of the salivary and lacrimal glands. Think dry eyes, dry mouth, maybe associated with a connective tissue disorder. Periductal lymphocytic and plasma cell infiltrates.
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What are the general features of salivary gland tumors?
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Tumor arise most commonly in the major salivary glands, but are uncommon overall. Parotid affected the most, usually older adults. In parotid, most are benign. In other major glands, most are malignant. The larger the tumor, the less likely it is to be malignant.
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What are the benign tumors of the salivary gland? Important features of each?
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Pleomorphic adenoma and Warthin Tumor.
Pleomorphic adenoma: most common tumor of the parotid, histology varies (hence pleomorphic). Painless, slow growing masses. Warthin Tumor: 2nd most common tumor of salivary glands, more common in males. Smoking is risk. Also a parotid tumor, histology shows lymphocytes and cystic spaces. Papillary structure |
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What are the malignant tumors of the salivary gland? Important features of each?
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Mucoepidermoid carcinoma and adenoid cystic carcinoma.
Mucoepidermoid carcinoma: most common primary malignant salivary tumor, #1 parotid tumor in kids. Mix of squamous and mucus cells. Low grade and high grade, very different prognosis. Adenoic cystic carcinoma: uncommon, slow growing painful mass, can be cribiform or solid. Very lethal. |
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What is head and neck squamous cell carcinoma?
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Vast majority of head and neck cancers are HNSCC, and most occur in the oral cavity. White plaquey lesion is the precursor to cancer (leukoplakia). Incidence due to HPV infection is on the rise, incidence due to alcohol/tobacco use is falling.
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What is the role of the enteric nervous system?
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The enteric nervous system is found in the wall of the GI tract. Made up of the myenteric plexus in between the muscle layers, and the submucosal plexus in between circular muscles and mucosa. Autonomic system is integrated to promote or stop digestion.
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What are the stages in swallowing?
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preparatory phase: voluntarily ingest food
transfer: reflexes in the oral cavity and pharynx push food into the esophagus transport: bolus moves from esophagus to stomach Inhibition of respiration and closure of the epiglottis are part of the reflex, peristalsis involves relaxation ahead of the bolus and contraction behind it. |
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What type of muscle is in the esophagus? What type of neurons are in the myenteric plexus here and how do they contribute to peristalsis?
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Most proximal is striated muscle, then the rest of it is smooth muscle. Parasympathetics control peristalsis through the vagus nerve, cholinergic neurons release Ach to stimulate contraction and other motor neurons release NO and VIP to relax muscles. Inhibition occurs first, lasts longer in the lower parts of the esophagus, then activation occurs.
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How does the LES contribute to gastric motility?
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The LES is normally closed and contracted. When you swallow, the sphincter relaxes. It is made up of smooth muscle and fibers from the diaphragm. Vagus release of Ach causes contraction, NO and VIP relax it.
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What types of contractions occur in the small intestine? In the large intestine?
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Small intestine: sustained contractions of the circular muscles, local events. This is important in mixing the chyme. Also have peristalsis to move it forward.
Large intestine: segmental contractions and mass movement, which happens 1-3 times a day to push everything through the colon. |
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What are the sphincters in the GI tract?
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upper esophageal, lower esophageal, pyloric, sphincter of Oodi, ileocecal, internal anal, and external anal.
UES and external anal are striated muscle, all others are smooth. |
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What are the congenital malformations of the esophagus?
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Esophageal atresia: lumen does not form a canal, becomes closed at one end. Associated with hydramnios and premature birth. More commonly seen with a tracheoesophageal fistula than pure esophageal atresia.
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What are the differences between a Mallory-Weiss tear and Boerhaave Syndrome?
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Mallory-Weiss tear is due to forceful vomiting, often seen in alcoholics. Longitudinal tear at the GE junction. Typically see hematemesis, should not cause pain.
Boerhaave Syndrome is less common and can be lethal. Here, you have chest pain, pain with swallowing, and no bleeding. Tear can lead to infection of the mediastinum. |
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What is GERD? What causes it? Clinical presentation?
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GERD = gastroesophageal reflux disease. Very common, causes heartburn, chest pain, indigestion, etc. Something is preventing the normal reflux defense from working correctly, and so the gastric contents irritate the esophagus. Disorder of motility
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What is tLESR? What are some other causes of reflux?
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tLESR = transient lower esophageal sphincter relaxation, this is the most important etiology for GERD. These relaxations occur independent of swallowing/peristalsis and last for a longer time.
Other mechanisms include hypotensive LES pressure (affected by various hormones, foods, drugs). Could also be due to increased ab pressure from pregnancy or obesity, or a hiatal hernia. |
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What is reflux esophagitis? Histological findings? What are infectious causes of esophagitis?
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Inflammation of the esophagus due to reflux from the stomach. Neutrophils and eosinophils infiltrate, hyperplasia of the basal zone, and papillary elongation.
Infectious causes include candidiasis and herpes, both more common in immunocompromised. Candida: nodular, uclerated mucosa with a colored pseudomembrane. See necrosis and fungal parts. Herpes: punched out lesions with elevated rim. |
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What is eosinophilic esophagitis? How do we treat?
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EE is non-infectious disorder, see classic symptoms of dysphagia and heartburn. Co-morbidities with asthma, atopic dermatitis, etc. See a dense infiltrate of eosinophils (>15 on high power), microabscesses, and basal zone hyperplasia. Treat with PPIs, steroids, and dilation.
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What is Barrett's esophagus?
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This is a type of metaplasia (reversible change in cell type). Squamous > columnar epithelium. Due to chronic reflux. Has a bimodal age distribution, more common in males. 10% risk for GERD pts, and those with Barrett's have increased risk of adenocarcinoma.
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What are the 2 types of esophageal malignancies?
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Esophageal adenocarcinoma: most common esophageal cancer, think older men. Almost all associated with Barrett's. Alcohol, tobacco are risk factors. Low survival because symptoms come on once disease has progressed. Begin at GE junction!
Esophageal squamous cell carcinoma: less common, vitamin deficiencies + etoh and smoking are risk factors. More common in blacks. More proximal than adeno. Both have symptoms of dysphagia, anorexia, and weight loss. |
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What are the 2 general mechanisms that lead to dysphagia? Give an example of each type.
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Dysphagia = difficulty swallowing. Problem can be mechanical or due to altered motility.
Schatzki ring/B ring: associated with hiatal hernias, found near the GE junction. Circular projection into the lumen. Very common. Achalasia: motility disorder due to dysfunction of the LES, it does not relax when it should. Due to chronic inflammation that results in loss of inhibitory motor neurons (NO). May be autoimmune. |
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What are the main functions of the stomach? What are the anatomical regions?
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Motor (mixing food, storing it, emptying, vomiting), secretory (HCl, mucus, pepsinogen, IF), regulatory (gastrin, somatostatin, histamine, Ach).
Fundus: at top Body: middle, secrete HCl, mucus, pepsinogen Antrum: bottom near duodenum, secretes gastrin, mucus, pepsinogen. |
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For each hormone, identify where it comes from and what it does.
gastrin, CCK, secretin, gastrin releasing peptide, somatostatin |
gastrin: produced by G cells in the antrum, acts on parietal cells and ECL cells to stimulate acid secretion.
CCK: made in the duodenum and jejunum after stimulation by fatty acids, acts to contract gall bladder and stimulate pancreatic enzyme secretion secretin: made in the duodenum, stimulated by low pH, FA and BA. Acts on the ducts to increase bicarb and fluid secretion. GRP: released by the vagus, acts in antrum to release gastrin somatostatin: made by D cells, acts on G/ECL/parietal cells to decrease release. |
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What is the function of the parietal cell? How is it regulated?
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Parietal cells are in the fundus and body, they secrete HCl. The proton pump spits out H+ (from water hydrolysis) and takes in K+ (this H/K ATPase gets blocked by PPIs), and a chloride co-transporter exists as well. The leftover OH- from hydrolysis leaves on the basolateral side as bicarb.
Regulation: vagus nerve delivers Ach or gastrin and histamine act to increase acid production. Peptides from food cause G cell to make gastrin, gastrin weakly hits parietal and strongly hits ECL cell to make histamine, histamine strongly hits parietal. |
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What are the 3 phases of gastric secretion?
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Cephalic (40%): happens before food is ingested, you see/smell think about food. Ach gets released from vagus, gastrin is released as a result.
Gastric: food hits the stomach, both vagus and protein digestion triggers the g cells. Intestinal: hormonally mediated in the small intestine |
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What are chief cells? What is intrinsic factor?
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Chief cells make pepsinogen, it is a precursor to pepsin. Pepsinogen release is stimulated by same things that stimulate gastrin release. Low pH allows conversion into pepsin, pepsin is only active at low pH, digests proteins.
Intrinsic factor is made by parietal cells, needed for B12 absorption. |
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What are the pre-epithelial, epithelial, and sub-epithelial defense mechanisms in the stomach?
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pre-epithelial: mucosa acts as a physical barrier, contains bi-carb to locally raise the pH, has hydrophobic phospholipids to protect from pepsin and acid.
epithelial: these cells secrete the mucus layer, tight junctions prevents disruption, and prostaglandins promote elements of the mucus layer and increase blood flow. sub-epithelial: vasodilators get released (increased activity during injury) to increase blood flow |
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What is the cause, histology, and other features of acute gastritis?
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think NSAID use, alcohol, h. pylori to a much lesser extent. See edema, congestion, inflammation. Can be hemorrhagic if severe, or have erosions and necrosis superficially.
NSAID can cause hemorrhagic or non-hemorrhagic. |
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What is the cause, histology, and other features of non-atrophic chronic gastritis?
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Non-atrophic aka Type B gastritis is the more common chronic type, due to H. pylori. Increased risk of MALT lymphoma. Antrum of the stomach is involved. These are the 15%.
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What is the cause, histology, and other features of atrophic chronic gastritis?
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Atrophic chronic gastritis is Type A, involving the fundus and gastric body. Autoimmune, antibodies hit parietal cells which leads to intestinal metaplasia, glandular destruction. Associated with pernicious anemia due to B12 deficiency (IF is also destroyed), achlorhydria (low gastric acid), risk of neuroendocrine gastric tumors.
Can also be environmental due to h pylori, risk of adenomcarcinoma. |
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What causes peptic ulcers? How is acid production changed with h pylori and how can we test for h pylori?
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Peptic ulcers either due to NSAID use (more in gastric ulcers) or h pylori (more common). H pylori is a bacteria that makes urease, can create a local alkaline environment.
In both acute infection and chronic pangastritis, there is increased SST, leading to decreased gastrin and acid. Low acid is most common. In some patients, h pylori results in high acid. These are to pts at risk for ulcers. Inflammation is concentrated to the antrum, and SST is low. Testing: serology, stool antigen, urea breath, biopsy |
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What other complications are associated with chronic h pylori infection?
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Type A/atrophic: gastric cancer, gastric ulcers
Type B/non-atrophic: MALT lymphoma antral gastritis: duodenal ulcers |
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How are duodenal ulcers different from gastric?
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duodenal: excess acid and h pylori
gastric ulcers: normal or low acid, primary mechanism is impaired mucosal defense |
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What are the topical vs systemic effects of NSAIDs?
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topical: acute. Drugs are weak acids in stomach that can diffuse into the gastric epithelial cells (unionized, lipid soluble). Once inside, they become ionized from neutral pH and can't leave. High concentration of NSAID inside kills the cell.
systemic: major cause of toxicity. COX is inhibited, can't produce prostaglandins anymore. No prostaglandins = more acid secretion, less bicarb and mucus, and less blood flow (most important). |
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What is Zollinger-Ellison syndrome?
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Rare cause of ulcer disease, due to gastrinomas (neuroendocrine tumors) that release tons of gastrin leading to high acids levels. Clinically, see ulcers in weird areas like distal dueodenum or jejunum, or see numerous ulcers. High gastrin in blood is a clue, treat with PPIs and surgery.
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What are fundic gland polyps, hyperplastic polyps, and neoplastic polyps?
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fundic gland: most common, increased with PPI use due to high levels of gastrin leading to glandular hyperplasia. Well circumscribed lesions, minimal inflammation, swiss cheese dilation on histology.
hyperplastic: small multiple elevations, incidental finding. Small risk of carcinoma. Similar to the polyps in colon. neoplastic: benign, single large lesion on a stalk. Dysplasia seen, high malignancy risk. |
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What is the most common type of gastric tumor?
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Gastric adenocarcinomas. Poor prognosis, increased in East Asians, symptoms late in disease course. Risk factors = h pylori, chronic atrophic gastritis, intestinal metaplasia
Bulky tumor with glandular like structures. Can also present as diffuse lesion with rigid, leather like structure. Cells here have a Signet ring appearance, occurs in younger males. |
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Antacids
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locally neutralize thanks to OH and bicarb, used for quick relief of stomach upset. Side effects are diarrhea (Mg), constipation (Al), motility and reflux (Ca). Can have renal or RX interactions. Don't last long.
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cytoprotectants MOA (sucralfate, bismuth compounds, misoprostol)
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physically form a barrier to protect mucosa, have no effect on pH.
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sucralfate
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given in ICU as prophylaxis for stress ulcers, can have constipation or chelation reactions like with antacids
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bismuth compounds
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pepto-bismol! Protection allows for ulcers to heal, can get dark tongue and stool, constipation. Do NOT take with aspirin allergy
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misoprostol
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a prostaglandin analouge, also given to induce pregnancy or abort. Acts by increased mucosal blood flow. Can cause diarrhea or miscarriage.
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H2 antagonists
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blocks the histamine receptors to suppress acid production, longer acting drug can produce fast effects. Use with ulcers, GERD, stress ulcer prophylaxis. Diarrhea, constipation, sedation, BM suppression side effects, must dose adjust for renal function
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Cimetidine
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an H2 antagonist, but requires more dosing, interacts with cytochrome p450, and causes gynecomastia. Think about drug interactions with this, it is an inhibitor.
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PPIs (omeprazole)
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irreversible inhibition of proton pump, has long duration of action but delyaed onset. Absorbed into bloodstream to act. Use for GERD, ulcers, or ZES. Side effects of GI upset, decreased nutrient absorption, C diff overgrowth, GI tumors.
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metoclopramide
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a prokinetic drug, this class increases release of acetyl choline to reduce symptoms. Can be Ach agonists or dopamine antagoinsts, serotonin modulators. Metoclopramide is a dopamine antagonist. Side effects are extrapyramidal, don't use if you have Parkinson's.
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What is bile? What are bile acids?
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BILE = bile acid + phospholipids + cholesterol + pigments. Needed for digestion/absorption of lipids.
Bile acids are made from cholesterol (cholic acid + derivatives) and are structurally similar. Key because of amphipathic nature, 1 side is charged and other is uncharged. |
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What is the enterohepatic circulation for bile acids?
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The gallbladder empties bile acids into the small intestine after a meal. Acids travel through tracts digesting/absorping lipids, then get taken up in the terminal ileum and sent back to the liver. Hepatocytes remove the bile acids from the blood to be used again. Both sites of absorption require energy.
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What are micelles?
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Spheres of bile acids, phospholipids, cholesterol. No pigments in a micelle. Acts as a ferry to transport these substances in the GI tract. Phospholipids that are normally crystal become soluble in a micelle, cholesterol becomes soluble too.
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What are bile acid dependent and independent secreted by the liver?
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There are 2 main components to bile secretions by the liver.
Bile acid dependent: bile acids are ionized, and when hepatocytes secrete them an osmotic gradient is formed. Water flows, along with electrolytes. Bile acid independent: as bile flows through ducts, its composition changes. |
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What pigments are in bile? How are they formed?
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Bilirubin. Formed from breakdown of RBCs (heme ring gets iron removed), transported by albumin, gets conjugated with 2-glucuronic acid in the liver, then sent to GI to get reabsorbed or secreted. Can also go to kidneys to be excreted as urobilinogen. Secretortion is the rate limiting step.
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What hormone regulates contraction of the gall bladder?
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Lipids and other products of food digestion stimulate the release of CCK from the duodenum, which stimulates gall bladder contraction.
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What are the primary bile acids? Secondary bile acids?
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Cholic + chenodeoxycholic acid = primary
deoxycholic + lithocholic acid = secondary Primary are made by hepatocytes, and amount synthesized is dependent on enterohepatic return (low return means high synthesis). Secondary are made in the intestine by microorganisms. |
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How are gallstones formed? What are the most common types of gallstones?
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Gallstones are formed when there is too much cholesterol, or not enough bile acids/phospholipids. Most common type is cholesterol gallstone, can also have bilirubin stones (often seen in chronic hemolytic states). Cholesterol is made by heptaocytes, and eliminated by bile acids. Normally cholesterol is soluble in the micelle, but if cholesterol precipitates out of bile, gallstones form.
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How does gallbladder motility and pronucleators contribute to the formation of cholesterol gallstones?
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If a gallbladder is not very motile, cholesterol crystals have a better chance of clumping together and forming larger gallstones. Mucin is normally produced to protect the gall bladder, but can act as a pronucleator that promotes crystal aggregation.
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What are the major risk factors for cholesterol gall stone formation? Explain the pathogenesis.
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Older age, females, obesity, weight loss, pregnancy, birth control, Native Americans & Scandinavians are all due to increased cholesterol secretion.
TPN is a risk due to gallbladder hypomotility. Diseases of the terminal ileum lead to reduced bile acids. |
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Describe the following clinical scenarios.
choledocholithiasis cholangitis cholecystitis gallstone pancreatitis |
choledocholithiasis: gallstones present in the bile duct. Can lead to inflammation of the gall bladder (cholecystitis), elevated LFTS, and pancreatitis, all depending on location of the stone.
cholangitis: infection of the bile ducts due to stone obstruction cholecystitis: infection of gallbladder due to cystic duct obstruction gallstone pancreatitis: if stone at at the Ampulla |
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What is the clinical presentation of gallstone disease?
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Biliary colic = RUQ pain that is dull/pressure like, associated with N/V, sweating. If there is fever, elevated LFTS and WBC count, think cholecystitis (inflammation due to blockage). US, CT, and MRI are all useful in finding gallstones. Treat with lifestyle changes (obesity), avoiding medications. Medical therapy is not great, surgery better.
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What is the structure/function of the pancreas? What do acinar vs duct cells secrete? What stimulates pancreatic secretion?
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Pancreas is a large gland that is exocrine into the duodenum, and endocrine into the portal blood. Acinar cells secrete a set of enzymes needed for digestion of most of the molecules found in our food, water and chloride. Duct cells secrete watery solution that contains bicarb and Na+. Resulting juice is alkaline, enzyme rich.
Vagal signals, CCK (enzymes), secretin (bicarb) |
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How does the secretory rate of the pancreas affect the concentration of Cl- and HCO3- in the pancreatic fluid?
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Pancreatic fluid is isotonic with plasma, and osmolality does not depend on rate of flow. This is because the concentration of Cl- and HCO3- vary inversely to one another.
At high flow, bicarb > Cl- At low flow, Cl- > bicarb |
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What are the key enzymes in pancreatic juice?
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a-amylase: digests starch, is secreted in the active form
lipase, phopholipase A, colipase: digests fats proteases: digests protein, secreted as proenzymes or zymogens, activated by trypsinogen trypsinogen: the master enzyme, converted to trypsin (enterokinase secreted from duodenal mucosa) to turn on proteases and make more trypsinogen |
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What mechanisms are in place to prevent the pancreas from digesting itself?
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The proteases that attack membranes are secreted in the inactive form. Enzymes are segregated in special compartments. There is trypsin inhibitor in case trypsinogen gets activated. Enterokinase is purposely separate from the pancreas.
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What happens to pancreatic secretion in the cephalic, gastric, and intestinal phases of digestion?
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Cephalic phase: pancreatic secretion released, rich in enzymes, low in aqueous. Due to vagal stimulation.
Gastric phase: gastrin and vagal stimulation lead to secretion Intestinal phase: This accounts for the majority of pancreatic secretion, thanks to chyme in the duodenum. CCK and secretin are released, both of which increase pancreatic secretion. |
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What are the roles of CCK and secretin?
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Secretin: this is nature's antacid, it acts to stimulate the electrolyte part of pancreatic juice (bicarb), also decreases acid and increases bile. Main stimulator is HCl, not stimulated by amino acids or peptides!! Comes from S cells in duodenum. Important in causing alkaline environment for enzymes to function in.
CCK: this is the main stimulator of pancreatic enzymes, only weakly activated by acid (unlike secretin). Also contracts gallbladder, comes from I cells in response to digested amino acids and fatty acids. |
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Why is the anatomic location of the pancreas important for pathophysiology?
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Pancreas is retroperitoneal and close to numerous digestive organs. Pancreatic duct empties through the Ampulla of Vater (with common bile duct), and common bile duct is behind/through the pancreas. Disease of bile duct or pancreas can affect close organs.
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What is acute pancreatitis? 3 most common causes?
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Inflammation from loss of protective mechanisms, enzymes are digesting tissue. Can be mild with edema, or severe with necrosis and hemorrhage. Alcohol, gallstones, and idiopathic. Alcohol can stimulate enzymes and plugs block secretion, gall stones can obstruct duct temporarily and cause activation of enzymes
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What is the pathophysiology of acute pancreatitis?
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Pancreatic enzymes get activated by trypsin, because the trypsinogen inhibitor is overwhelmed. Something has stimulated the enzymes, and also prevents the release of the enzymes from the acincar cells, so the enzymes stay in the interstitium and destroy things. Cytokines get activated, and systemic inflammation occurs.
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What are the clinical manifestations of acute pancreatitis? How can we diagnose?
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Different if mild or severe. Mild = abdom pain (crouched over, avoiding lying down on back), elevated lipase and amylase. Severe = fat necrosis (lipase is in the blood stream), hemorrhage, hypocalcemia, shock, ARDS
Diagnose: amylase and lipase (more specific), level of elevation does NOT equal severity, imaging |
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What are the potential complications of acute pancreatitis?
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Many of the complications are due to the systemic inflammatory response. Activation of bradykinin = capillary leakage/vasodilation, complement , thrombin = coagulation, phospholipases = cell membrane damage. Can cause shock, acidosis from poor perfusion, ARDS, renal failure, DIC, hyperglycemia, hypocalcemia. Later on get multiorgan failure and infection (necrosis and abscess formation). Prognosis determined by Ranson criteria.
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What are pseudocysts?
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Pockets of pancreatic secretions inside or around the pancreas, become a late stage problem. Can lead to pain, infection, etc. Develops in the setting of pancreatitis. In acute, takes weeks to develop. No epithelial lining, lined by granulation tissue/fibrous tissue.
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What is the treatment for acute pancreatitis?
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Goals are the replace fluid and electrolytes, to help control the pain, and to closely observe in ICU for any complications. Need tons of IV fluid because of leaky capillaries (bradykinin). May need surgery if necrotic tissue, abscesses, or gallstones.
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What is chronic pancreatitis? What is the causes?
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Damage to the pancreas that is permenant and irreversible, see fibrosis and destruction. Ducts become narrowed or dilated, may see stones. Alcohol abuse is #1 cause, but it is NOT due to several acute attacks, takes years for it to occur and not fully explained by alcohol alone.
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What is the pathophysiology of chronic pancreatitis?
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Several theories, probably a combo. Ductal obstruction from alcohol leads to protein plugs and obstruction of ductal cells. Toxic-metabolites from alcohol may directly damage cells leading to fibrosis. Repeated episodes of acute pancreatitis may cause a cycle of inflammation>necrosis>healing>fibrosis. Genetic mutations increase risk, CFTR causes decreased bicarb secretion which leads to chronic pancreatitis.
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What are the four clinical manifestations of chronic pancreatitis? How do we treat?
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1. Pain due to increased pressure behind obstructed ducts
2. Malabsorption due to loss of pancreatic enzymes, can compensate for protein and carbs but fat is an issue, get steatorrhea 3. Weight loss due to the fat malabsorption 4. Diabetes mellitus from loss of endocrine function Treat by stopping cigarettes and EtOH, give enzymes and pain management, insulin for diabetes, nerve blocks |
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How is chronic pancreatitis diagnosed?
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PE and labs not diagnosticl. Tests of pancreatic function are, includes measuring enzyme levels in pancreatic juice or indirectly in blood or stool. Imaging is helpful, can use plain film (calcification), US, CT, or ERCP (dilations). Problem is the tests work best when detecting severe disease.
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What is pancreatic divisum? Other congenital anomalies?
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Most common congenital anomaly of the pancreas.Dorsal and ventral bud from midgut fuse together. If they don't fuse, main duct isnt' used and drainage occurs through accessory duct. Can cause duct stenosis or chronic pancreatitis.
Annular pancreas: incorrect fusion forms a ring around duodenum Ectopic pancreas: pancreatic tissue in gastric antrum, D, J, I |
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What is the most common cause of pancreatic cancer?
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Pancreatic ductal adenocarcinoma, affects the exocrine portion (head most common). Present with painless jaundice. Common cause of death from cancer. Has a very poor prognosis. Elderly smokers, chronic pancreatitis are risk factors. Clinical manifestations seen late in disease, epigastric pain, weight loss, jaundice (bile duct obstruction), diabetes, pancreatitis, Trosseau sign (migratory phlebitis). Can do Whipple procedure .
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What are the features of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms?
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Mucinous cystic neoplasms are more common in women, have a good prognosis. Looks similar to an ovarian neoplasm. IPMN are becoming more common, varying dysplasia and better prognosis, more common in men. Secrete mucin, can progress slowly to adenocarcinoma.
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What are the features of pancreatic endocrine tumors?
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These are much less common than ductal adenocarcinomas. These can cause clinical syndromes if tumor secretes hormones. Insulinoma is most common, benign. ZES is a gastrinoma. Check for metastases to see if it is malignant, no way to tell from histology.
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What types of cancer are seen in the bile ducts and gall bladder?
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Gallbladder: very rare, adenocarcinoma most common. Not due to gallstones, but may be related to influences that led to gallstones. Poor prognosis, discovered late.
Bile ducts: almost all are adenocarcinomas, small in size, produce obstruction symptoms early on. Spread into liver, pancreas, duodenum. Association with sclerosing cholangitis. |
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What structures in the intestine allow for digestion and absorption of nutrients?
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Surface area is huge thanks to folds, villi, and microvilli. pH is neutral to allow enzymes to function and prevents damage. Enterocytes absorb nutrients, goblet cells make mucin, endocrine cells release gastrin/secretin/CCK, stem cells, and Paneth cells make lyzosomes to kill bacteria.
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How does the function of the small intestine compare to the large?
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Small intestine: has a much greater surface area, digests nutrients on the surface of the cells (enterocytes), and absorbs nutrients, Na+, and water.
Large intestine: much smaller surface area, does not digest anything and rarely absorbs nutrients, but majorly absorbs sodium and water |
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What are the major nutrients absorbed in each part of the small intestine?
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Duodenum: only site for iron absorption, major site for carbs, protein, lipids, water, sodium
jejunum: carbs, protein, lipids, etc to a lesser extent ilieum: cobalamin and bile acids |
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How is starch digested and absorbed?
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Cellulose is the only starch that can't be digested. Digestion starts in mouth with amylase, continues in duodenum with amylase which turns them into the "oses". Ends products are glucose, galactose, and fructose. Transported into cells with Na cotransporter.
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How is protein digested and absorbed?
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Protein gets broken down into small peptides, large peptides, and amino acids starting in the stomach thanks to pepsin. Small peptides and amino acids can be absorbed by carriers, large peptides must be further broken down. Na+ transporter here as well.
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How are lipids digested and absorbed?
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Micelles allow fats to become soluble. Ipase digests triglycerides into free fatty acids and monoglyceride. Glycerol can enter cell on its own, micelles enter and triglycerides get re-synthesized and packaed into chylomicrons. Chylomicrons leave through lymphatics.
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What is osmotic diarrhea? What are the common causes?
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Osmotic diarrhea is loose, watery, smells, but improves if you stop eating. Idea is that if you have too many substances that are osmotically active in the lumen, water will be retained. Electrolytes are NOT affected, should have low Na and K. Lactose intolerance is classic example.
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How do you calculate the fecal osmotic gap? How do you interpet it?
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Fecal osmotic gap is 290 - 2 X (Na+K). If it is >125, it is osmotic diarrhea because Na and K will be low in the stool. If it is < 50 it is secretory diarrhea.
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What are the features of lactose intolerance?
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Abdominal bloating and osmotic diarrhea. Missing or deficient lactase enzyme, lactose doesn't get broken down, bacteria ferment it. Acquired > congenital. Diagnose with late peak hydrogen breath test. Treat by avoiding lcatose or eating dairy with lactase added.
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What is small intestinal bacterial overgrowth syndrome? What type of diarrhea does it cause?
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Basically have too much bacteria. Can be due to intestinal stasis from surgery, structures, motility disorders; or from an abnormal connection between the proximal and distal bowel. Problem is that too much bacteria inactivate bile salts, so fats are not absorbed. Get malabsorption diarrhea. Dx with hydrogen test, early peak.
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What are the features of malabsorption diarrhea?
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Due to bile acids ending up in the colon. Bile acids irritate the colon (detergent) which causes increased sodium/water secretion, motility, and damage.Sudan stain should be positive. Also seen with bacterial overgrowth.
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What is Celiac Disease? Etiology? Symptoms? Associated conditions? Dx & Rx?
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Sensitivity to gluten, more common in Northern Europeans. Due to T-cell chronic inflammation in proximal small intestine (lamina propria). See flattened mucosa, villi loss, lymphocytes in LP. HLADQ2 or 8 association. See cramping, chronic diarrhea, bloating, weight loss, steatorrhea. May lead to osteoporosis, iron deficiency, peripheral neuropathies but severity can vary. Dermatitis herpetiformis, some cancers are associated. Dx with positive tissue transglutaminase antibodies (IgA more sensitive, can do biopsy if IgA deficient) or biopsy, treat with gluten free diet.
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What is secretory diarrhea? What are the common causes?
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Idea is ion transport is defective, so electrolytes do not get absorbed or they get secreted too much. Water follows the electrolytes. Fecal osmotic gap will be < 50. Can be due to bacterial toxins, laxatives, congenital defects, carcinoid tumors, intestinal resection, dissue mucosal disease that prevents enterocytes from absorbing electrolytes, or abnormal mediators.
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What 2 syndromes lead to secretory diarrhea because of the abnormal mediators?
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Zellinger-Ellison and Carcinoid.
ZES: too much gastrin, acid inactivates enzymes and bile acids Carcinoid Syndrome: secrete serotonin, bradykinin, prostaglandins, etc. These are gastricneuroendocrine tumors, most common in small intestine. See diarrhea, flushing, right side heart failure, bronchoconstriction in the syndrome (liver metastasis). |
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What is diarrhea due to altered motility? What are the common causes?
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Anything that changes the motor activity can lead to diarrhea, because there is less time for normal digestion to occur. Diabetics, hyperthyroidism, hypothyroidism, IBS.
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What is IBS?
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A syndrome with abdominal pain that improves with defecation, and onset is associated with change in frequency or form of the stool. Can be constipation or diarrhea. Pretty common, moreso in females. May be due to brain-gut communication issue, hyperresponsiveness.
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What 2 major disorders make up inflammatory bowel diseases? How are they similar and different?
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Ulcerative colitis and Crohn's Disease, both have equal incidence.
Similar: due to an interplay btw genetics, environmental triggers, and immune dysregulation. Different:UC is limited to the mucosal layer of the colon, Crohn's is transmural inflammation that can involve the entire GI tract. |
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How does genetics play a role in IBD? Inflammation?
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In general, IBD tends to run in families, with concordance for the same disease. Lots of genes being investigated, NOD2/CARD15 thought to increase the inflammatory response, found in 30% of Crohn's patients (especially ileum type).
TNFa and IFNy are proinflammatory, associated with IBD and dominate. |
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What are the symptoms of ulcerative colitis? How do we diagnose?
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Bloody diarrhea (almost all have this), LLQ pain, urgency to defecate, frequent small BMs. Can have mild-severe disease. PE can be normal. Diagnose with clinical history, endoscopy (continuous diffuse distribution from rectum, superficial mucosal ulcerations and erythema), p-ANCA + & ASCA -.
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How does the pathology of UC compare to the pathology of CD?
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UC: colon only, broad based ulceration, pseudopolyps, no strictures, no granulomas
CD: lesions are more focal, cobblestone appearance, granulomas (non-caseating),mesenteric fat extends around serosa, thickening of the bowel wall, transmural Both: cyrpt distortion, inflammatory infiltrates, crypt abscesses |
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What are some of the complications of ulcerative colitis?
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Toxic megacolon, hemorrhage, colon cancer (risk increases with disease duration and if pancolitis, need regular screening).
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What are the clinical symptoms of Crohns disease? What are the 3 categories of CD?
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Clinical signs are more varied than in UC. Pain in RLQ, large volume non-bloody diarrhea, cramps, vomiting, weight loss, fever, not as much urgency. p-ANCA - and ASCA +. Ileum and right colon most commonly involved.
Inflammatory: diarrhea and pain fibro-stenotic: strictures lead to obstruction, more symptoms fistula: can lead to abscess formation, perianal disease |
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What is the disease course of CD like? How do we diagnose?
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Majority of pts with CD will need surgery, recurrence is common, and it is a chronic disease with flares and remission. Dx with clinical history, barium study (string sign), MRI, CT, colonoscopy, serology (ASCA +)
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How do we treat IBD?
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5-ASA drugs, corticosteroids, antibiotics for fistulas and abscesses, 6-mercaptopurine and AZA, biologics (Infliximab). 50% of pts will need surgery, less recurrence post surgery for UC than CD.
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What are the major functions of the liver?
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The liver filters, synthesizes, metabolizes, stores and excretes substances:
Filtration: blood Synthesize: bile, proteins Metabolizes: nutrients, medications Stores: glycogen, vitamins, minerals Excretes: bile, cholesterol, hormones, drugs |
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Describe the anatomy, blood supply, and cell types of the liver.
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The liver is supplied by the portal vein and hepatic artery, drained by the central veins > hepatic veins > systemic circulation. Hepatocytes synthesize proteins and bile acids, cholangiocytes modify bile, Kupffer cells are like macrophages that help filter blood.
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Define the following terms.
glycogenesis glycogenolysis gluconeogenesis |
glycogenesis: glucose, fructose, and galactose get converted into glycogen which gets stored in the liver and muscle.
glycogenolysis: if there is a decrease in carb intake and a glucose deficit, glycogen will get broken down to maintain glucose levels in the blood gluconeogenesis: the liver creates glucose from fats or proteins like alanine +other amino acids. |
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What proteins does the liver make, and why are they important? What lipids does the liver make, and why are they important?
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Proteins: Basically all blood proteins except for antibodies are made by the liver, albumin is most important. Albumin is a major contributor to plasma oncotic pressure (keeps blood in the vessels), and acts as a transporter.
Lipids: Liver make cholesterol and lipoproteins. |
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How is ammonia handled by the liver?
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Ammonia is toxic to the CNS, but is also a byproduct of digestion. Liver is home to the urea cycle, which converts ammonia into urea for excretion in the urine. In severe liver disease, ammonia can build up in the blood.
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How does the liver deal with bilirubin, steroids, and drugs?
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Bilirubin: albumin brings unconjugated/indirect bilirubin to the liver after RBC hemolysis. The liver conjugates it with glucuronic acid, which makes bilirubin water soluble and able to be excreted in bile
Steroids: numerous mechanisms for inactivation in liver, hormones then become hydrophilic and get excreted in urine Drugs: Phase 1 is fast, polar groups added or taken away leads to activation or inactivation of the drug. Phase 2 is slow, get detoxification of the drug |
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What are the broad categories of liver disease?
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hepatocellular: the hepatocytes are primarily affected, hepatitis means there is damage and destruction of hepatocytes due to inflammation. Can also be ischemic due to hypotension or heart failure (zone 3 at greatest risk).
cholestatic: excretory and secretory function is compromised, bile formation and flow is affected. infiltrative: cells and tissue that shouldn't be there (cancer, granulomas, amyloid) cirrhotic: end stage of many chronic diseases, cell loss + scar tissue |
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What types of LFTs are there? What do they measure? What are some of the caveats about LFTs?
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Excretion and detoxification: measured by bilirubin and ammonia levels.
Synthesis: albumin and clotting factors Hepatocyte damage: ALT and AST Regurgitate from liver cells if impaired bile flow: alkaline phosphatase, GGT Can also look at Ig and antibodies for autoimmune liver diseases. Problem with LFTs is that they can be nonspecific, insensitive. Best use is to ID a pattern, and use them in conjunction with one another. |
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Describe the synthesis, and metabolism of bilirubin. How do we measure it?
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Bilirubin comes from hemoglobin metabolism, formed in the reticuloendothelial cells (heme >biliverdin>bilirubin). Albumin transports it to the liver as unconjugated BR, where it binds to a transporter and enters hepatocytes. Inside, becomes conjugated and hydrophylic, then actively transported out by MRP2 (rate limiting step). Enters bile, becomes unconjugated in distal ileum by bacteria and reduced to urobilinogen (most excreted as feces, some as urine or some reabsorbed). Can measure direct, indirect, and total.
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What are some of the causes of an elevated bilirubin?
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Increased production: anything where RBCs are destroyed, think hemolysis, thalassemias. Direct will be normal, indirect will be high.
Decreased conjugation: see normal direct, high indirect. Gilbert's Syndrome is common, gene abnormality leads to slight decrease in rate of conjugation. Crigler-Najjar syndrome is serious, UDP is defective. Decreased excretion: both are elevated, see bilirubin in urine. All types of severe liver disease. |
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What is the measurement of ammonia useful for?
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Not much. Ammonia is toxic, can be made into urea or converted into glutamine. Ammonia measurement is unreliable, can be high due to crush injury, poor circulation, etc.
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What tests are used to measure biosynthesis function of the liver?
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Albumin & Clotting Factors.
albumin: long half life, good measure for chronic not acute. Not specific for liver disease, hypoalbunemia also seen in protein malnutrition, nephrotic syndrome, chronic infections (cytokine released can inhibit albumin synthesis). Clotting factors: All factors except VII are made in liver, short half life makes this best test for acute liver function. PT/INR is most useful. |
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What are AST/ALT used for?
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Aspartate aminotransferase and alanine aminotransferase. ALT in liver, AST in a lot of places (less specific for liver disease). Good for acute hepatocellular injury. Absolute elevation is not helpful. ALT should be higher than AST, except with alcohol. If AST:ALT is >3:1 ratio, and levels are below 300, think alcohol. If AST and ALT are >1000, think major injury.
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What is the alkaline phosphatase test useful for? What other tests are associated?
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Found in or near bile membrane of hepatocytes. Tend to be elevated in childhood. If elevated, need to find the source of the problem. You can do electrophoresis for isoenzymes, but 5'NT and GGT are more commonly done.
5'NT: used to support liver as cause of AP elevation GGT: low specificity, only use to confirm liver source of AP elevation or alcohol abuse. |
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For each of the following serum proteins, ID what disease it is used to help diagnose.
gamma globulins antimitochondrial antibody ceruloplasmin alpha-1-antitrypsin ferritin |
gamma globulins: increased in chronic liver disease, if diffuse polyclonal increase in IgG think autoimmune hepatitis.
AMA: a marker for primary biliary cirrhosis ceruloplasmin: Wilson's disease, an inherited disorder of copper metabolism alpha-1-antitrypsin: protein is made by liver, low levels in alpha-1-antitrypsin deficiency ferritin: very high in hemochromatosis but non-specific for liver disease |
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What are the 3 patterns of LFT abnormalities and associated differentials?
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Hepatocellular: elevated transaminases, because there is damage to the hepatocytes. Dramatic increases in acute viral hepatitis, ischemic disease, AIH, toxin injury. Mild elevations with alcoholic disease, chronic hepatitis, fatty liver.
Cholestatic: AP elevation, 5' NT elevation. Bilirubin normal early on, increased with advanced disease. Think biliary obstruction, cancer, AIDS cholangiopathy, infiltrative disease. Mixed: both transaminases and AP are elevated, usually mild. Gallstones and drug induced injury are common causes. |
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What is the structure of an acinus? What are the zones?
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Acnius is a metabolic lobule, extends from portal triad (bile duct, hepatic artery, portal vein) to the hepatic vein. Sinusoids drain to the central vein and face basolateral side of hepatocytes, bile canaliculus drain from the apical side of the hepatocytes. Zone 1 is closest to triad, affected 1st by viral hepatitis. Zone 2 is intermediate, Zone 3 is close to the central vein and is affected 1st by ischemia, has p450 system, most sensitive to toxins and alcoholic hepatitis.
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What are the pathological features of cirrhosis?
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Cirrhosis is end stage liver damage. See bands of fibrosis and nodules of hepatocytes, smooth appearance is lost. Stellate cells release TGF-B, which leads to fibrosis. The vascular architecture changes, leading to increased resistance and portal hypertension.
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What are the pathological/important features of alcoholic liver disease?
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This is the most common cause of liver disease in the US.
1.Can see a fatty liver, will be heavy and greasy, goes away with abstinence. 2. Alcoholic hepatitis can result from binge drinking, see swollen hepatocytes with Mallory bodies (damaged intermediate filaments), necrosis, acute inflammation. Presents with hepatomegaly that is painful and AST>ALT. 3. Cirrhosis is a long term complication of alcohol use in 10-20% of pts. |
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What are the pathological/important features of nonalcoholic fatty liver disease?
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Similar pathology to alcoholic liver disease in that you see fatty liver, hepatitis, or cirrhosis. Associated with obesity/diabetes/hyperlipidemia, but unlike alcoholic liver disease the ALT>AST. Diagnosis of exclusion. This has become the most common cause of chronic liver disease in the US!
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What are the pathological/important features of hemochromatosis?
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Too much iron leads to deposition in tissues and damage from free radical formation. Can be hereditary or due to chronic transfusions. Iron freely enters blood from enterocytes due to hepcidin deficiency (hepcidin should prevent Fe release). HFE gene mutation is most common (C282Y). Symptoms usually appear later in life, triad of cirrhosis, diabetes, and bronze skin. Can also cause cardiac arrhythmia's, arthritis, hypogonadism. Pathology shows brown pigment in hepatocytes, prussian blue stain to confirm. Phlebotomy for Rx.
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What are the pathological/important features of Wilson's disease?
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Buildup of copper in the brain and liver, presents in childhood with cirrhosis, neuro manifestations, and Kayser-Fleisher rings in the cornea. The liver disease can be highly variable and non-specific on morphology. Diagnose with low ceruloplasmin, increased copper in liver and urine, and genetic testing for ATP7B mutation. Rx with D-penicillamine (chelation).
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What are the pathological/important features of primary biliary cirrhosis?
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Autoimmune disease, granulomas in intrahepatic bile ducts. Middle aged women, unknown etiology. Presents with pruritis (due to circulating bile acids), fatigue, hepatomegaly, xanthomas. Other autoimmune diseases are associated, AMA is + in most patients! Pathology shows focal and variable changes, chronic non-suppurative cholangitis. Rx is ursodeoxycholic acid.
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What are the pathological/important features of primary sclerosing cholangitis?
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Inflammation and fibrosis of intrahepatic and extrahepatic ducts. Get a beaded appearance and onion skin fibrosis. Autoimmune mediated. Middle aged males, associated with ulcerative colitis. Increased risk of cholangiocarcinoma and colon cancer.
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What are the pathological/important features of auto-immune hepatitis?
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Chronic disease, can present abruptly. Young-middle aged women, associated with other autoimmune diseases, responsive to immunosuppressants. Hepatitis pattern on histology.
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What are the pathological features of drug/toxin induced liver injury?
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Literally can result in any pattern of liver injury. Always do thorough drug/exposure history. Can lead to hepatocellular damage, vascular disease, tumors. Can be acute or insidious. Worst outcome is massive necrosis with acute liver failure.
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What are the pathological/important features of hepatic adenoma? Hemangioma?
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hepatic adenoma: Benign tumor of hepatocytes, associated with birth control pills. Risk of rupture in pregnancy. Think young women. Can progress to malignancy.
hemangioma: not cancerous, found incidentally, more common in women |
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What are the pathological/important features of hepatocellular carcinoma? Most common cancer?
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Malignant tumor of hepatocytes, common world wide, associated with HBV infection. Other risk factors include any type of cirrhosis, alatoxins from Aspergillus. Alphafetoprotein is elevated.
Most common in liver is metastasis!! |
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What is hepatitis? What are the clinical features of acute and chronic hepatitis?
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Hepatitis is inflammation of the liver, see lymphocytes in response to damage (not just viral). ALT & AST are high, may get liver failure.
Acute: long incubation period, prodrome phase of flu like symptoms, illness phase with dark urine, jaundice, RUQ pain, and then recovery. Outcome is immunity, chronic or fulminant hepatitis. Chronic: evidence of hepatitis for more than 6 months. Causes fibrosis, can lead to cirrhosis or HCC. |
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Important epidemiology & serology of hepatitis A?
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RNA virus, enteric, is endemic (nearly 100% infected by 15) in developing countries. See acute viral hepatitis with fever, jaundice, painful liver. Non-specific in kids, hard to Dx. Only 1% is fulminant, none become chronic.
anti-HAVIgM = active disease anti-HAV IgG = past infection, protective Vaccine now part of childhood immunizations, can give post-exposure prophylaxis within 2 weeks of exposure. |
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Important epidemiology of hepatitis B?
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DNA virus, parenteral. Big and Bad (very contagious). Large Dane particle with surface antigen, core antigen and HbeAg (marker of active disease). Numerous extra-hepatic complications (rash, arthritis, glomerulonephritis). Transmitted through blood, 6 disease states. Develops into chronic only 10%, more common with vertical transmission in pregnancy. Prevent with antivirals in 3rd trimester, passive IG and vaccine.
acute: most common cause of acute in US fulminant chronic: asymptomatic, persistent, active co-infection with HDV complications are cirrhosis and HCC (even in carriers). Vaccines given at birth, 1 & 6 months (get anti-HBs), treat with interferons/nucleoside analogs. |
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Describe the following serology for hepatitis B.
HbsAg Anti-HbsAg IgM anti-HBcAg IgG anti-HBcAg HBeAg Anti-HbeAg |
HbsAg: disease, live virus, can be chronic, acute or carrier
Anti-HbsAg: no active disease, immune and cured IgM anti-HBcAg: acute, new infection IgG anti-HBcAg: old infection, chronic or resolving, not protective HBeAg: highly infectious, virus is going cray Anti-HbeAg: lower infectivity |
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Important epidemiology & serology of hepatitis D?
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Transmitted by blood, needs HBV for replication. Infection in 2 ways.
1. co-infection with HBV in blood 2. super infection, infect a person with chronic HBV. More severe. Serology is not helpful here. |
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Important epidemiology & serology of hepatitis C?
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RNA virus, blood borne. #1 cause of chronic hepatitis in the US, majority of those exposed develop chronic hepatitis (leading cause for liver transplantation). 20% of chronic develop cirrhosis. Clinically mild infection. Treat with interferon and ribavirin, can screen for anti-HCV antibodies (but anti-bodies are not protective). Must screen baby boomers for HCV antibody. No vaccine.
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Important epidemiology & serology of hepatitis E?
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Similar to hep A in that it is enteric, fecal oral transmission with no chronic disease. Endemic in Asia, India, Africa, Central America. Very rare in the USA. Found in pockets of outbreak, often young adults. No vaccine is available. Reservoir in animals. Pregnant women have much greater risk of fulminant disease (20%). Serology is crap, need CDC to do it.
anti-HEV IgM = acute anti-HEV IgG = past infection |
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What is the pathophysiology of portal hypertension?
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Portal hypertension develops in patients with cirrhosis because of increased resistance and increased blood flow. Increased resistance is due to fibrosis and nodules in cirrhosis, but can be pre-hepatic/hepatic/post-hepatic in other diseases. Increased flow is due to increased vasodilators (NO), so splanchnic flow increases. Note than mean arterial pressure is low because of the vasodilators.
Change in P = Q x R |
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How do we diagnose portal hypertension?
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Need to calculate hepatic vein pressure gradient. >10 mmHg means there is portal hypertension.
HVPG = WHVP (wedge hepatic vein pressure, reflects portal pressure) - FHVP (free hepatic vein pressure). Can also look for esophageal varices. |
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What are the causes of pre-hepatic, intrahepatic, and post-hepatic portal hypertension?
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pre-hepatic: thrombosis of the portal of splenic vein, AV fistula
intrahepatic: can be pre/post or sinusoidal. Pre-sinusoidal will have a normal HVPG, due to schistosomiasis or sarcoidosis. Sinusoidal will have elevated HVPG, due to cirrhosis this is most common. Post-sinusoidal seen in Budd-Chiari, can't measure the pressure. Post-hepatic: HVPG will be normal (both FHVP and WHVP will be elevated), can be congenital web in the IVC or cardiac disease. |
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What are the common sites where collateral circulation develops in portal hypertension? How can we treat esophageal varices?
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Any vein that connects portal to systemic. Umbilical, hemorrhoidal, retroperitoneal, esophageal, and gastric.
With esophageal varices, rupture can be fatal. Treat with vasopressin and somatostatin to reduce flow to splanchnic, beta-blockers, band ligation. |
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What is the pathophysiology, Dx, and management of ascites?
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Ascites is due to increased sinusoidal pressure and decreased oncotic pressure due to low albumin levels. The liver is less able to clear vasodilators, so circulating blood volume drops. Cardiac output increases, and the RAAS is activated. Sodium is retained, and ascites + edema worsens. Diagnose with SAAG (>1.1 think a portal hypertension cause)
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What is the pathophysiology, Dx, and management of hepatic encephalopathy?
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Hepatic encephalopathy is due to metabolic abnormalities in the CNS, seen in fulminant or chronic liver disease. Graded on a scale of I to IV and asterixis. Some toxin that the liver is not clearing (ammonia, GABA, benzo-like substance) is hitting the brain. Treat by addressing underlying cause, lactulose (decreases ammonia), and protein restriction. Triggers can be GI bleed, infection, sedatives.
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What is the pathophysiology, Dx, and management of hepatorenal syndrome?
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Get azotemia (high BUN and creatinine) and oliguria (low urine) with advanced liver disease. See severe renal vasoconstriction without renal disease, but there is major vasodilation in the extra-renal circulation. May be due to some humoral agent that the liver is not clearing. Only treatment is transplantation.
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What is constipation? Common causes? How are Sitz mark studies interpreted?
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Constipation is difficulty in passing stool, symptoms may vary. Very common, especially in elderly. Causes include drugs (opiates, anti-cholinergics, anti-diarrheals, NSAIDs), hypothyroidism, hypocalcemia, luminal obstruction or abnormalities, IBS, or colonic inertia. Sitz marker study can distinguish btw colonic inertia and obstruction based on distribution of rings.
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What is diverticulosis? What complications can result, and what are the clinical manifestations?
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Diverticulosis is outpouching of the colon through the muscularis layer, more common to be left sided in US. Associated with low fiber, increased pressure, anatomy defects, aging. Mostly asymptomatic, may see bloating or pain. Bulk up stool with fiber to Rx.
Complications include bleeding and infection. Bleeding is painless, stops spontaneously. Infection is fever, LLQ pain, high WBC count. Do NOT do a colonoscopy, treat with antibiotics or surgery. Infection can lead to fistulas, abscess, etc. |
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What is appendicitis? Clinical presentation and treatment?
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Appendicitis is inflammation of the appendix, due to obstruction of the lumen. Presents with fever, pain over the appendix, nausea, vomiting. Treat with surgery, easy diagnosis.
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What are hemorrhoids? Pathogenesis? Symptoms? Treatment?
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Masses of vascular tissue that dilate and enlarge. Internal are covered by mucosa and are not painful, external are. Very common! Due to downward pressure from defecation. Pts present with painless red blood, usually with a BM. If painful, they are external. Treat with bulking agents, rubber band ligation, surgery.
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What are anal fissures, abscess, and fistulas?
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anal fissure: tear in the anal canal, most common in young people. Due to increased strain during defecation. Mostly posterior midline, if not may be due to Crohns or cancer. Treat with baths, stool bulking, topical NG.
anal abscess: infection of tissue next to anal canal, needs surgical drainage. Associated w/Crohns. anal fistula: associated with Crohns, cancer, radiation treatment. Hollow tract that drains blood, stool, pus. |
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What are the common types of ischemic bowel disease?
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Many vascular conditions can lead to ischemic bowel disease. Ischemic colitis is most common by far (elderly), see sudden onset of pain, then diarrhea, then rectal bleeding. Splenic flexure is at most risk because of watershed blood supply. Acute mesenteric ischemia is less common, more painful, bleeding is less common, and age varies, more likely due to hypercoaguable state.
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What are the phases of ischemic injury to the bowel? Types of infarction?
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First, hypoxic injury at the site of vascular compromise. Then, reperfusion injury occurs when blood flow is restored to the ischemic area. Most damage is due to reperfusion.
Infarction is first mucosal: this is mild, within 1 hr of injury. Transmural infarction later on, then chronic ischemia can mimic Crohns. |
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What are the two types of hamartomatous polyps?
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Juvenile polyps: found in young children, benign and random. If there are >5 polyps, it is Juvenile Polyposis Syndrome and there is increased risk of malignancy.
Peutz-Jeghers polyps: no malignant potential, polyps throughout the GI tract with mucocutaneous pigmentation. Increased risk of colorectal, breast, and ovarian cancer. |
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What are hyperplastic polyps? What are adenomatous polyps?
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hyperplastic: No malignant potential, show a serrated appearance on microscopy. These are the most common type of polyp, found in left colon.
adenomatous: neoplastic proliferation of glands, benign but have malignant potential. Can progress via the adenocarcinoma sequence. Tubular least risky, then tubulovillous, then villous is worst risk. |
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What is the adenocarcinoma sequence? What features increase the risk of carcinoma progression?
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This is the progression of normal mucosa/adenoma to a carcinoma.
1. APC mutation on chromosome 5 increases risk for polyp formation, can be a germline or somatic mutation. Need to knock out 2 copies of the gene. 2. k-Ras leads to polyp formation 3. p-53 and COX expression lead to carcinoma progression. Increased size, sessile growth, and villous histology. |
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What is familial adenomatous polyposis? Gardner Syndrome? Turcot Syndrome?
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AD disorder, get TONS of polyps. Due to the APC mutation. Must remove colon and rectum, otherwise major risk of malignancy before age 40.
Gardner: FAP with osteomas and fibromatosis Turcot: FAS with CNS tumors |
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What is the epidemiology of colorectal carcinoma? What are the 2 pathways? How do we stage? What is the tumor marker?
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Older adults, common cancer and deadly. Most come from the adenoma carcinoma sequencer, these are typically left sided. Can come about from microsatellite instability, less common and right sided. Need to screen and test for occult stool after 50, goal is to remove polyps before progression occurs.
T= tumor depth, T1 in submucosa T2 in muscle T3 past muscle N= lymph node spread M = metastasis CEA is marker for recurrence and treatment response, not screening. |
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What is hereditary nonpolyposis colorectal carcinoma?
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HNPCC is a genetic disease in which DNA repair enzymes are defective. Leads to instability in microsatellites and abnormal tissue growth. No transition from adeno, no polyps, just straight carcinoma. Carries increased risk of colorectal, ovarian, and endometrial cancer. Won't see protein expression on immunohistochemical stain.
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How do the bulk-forming agents work? What are they used for? Side effects?
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Add mass to the stool with fiber or by bringing water in. No systemic effects, just local bloating and pain. May bind to other medications if given at the same time.
Bismuth is also an antimicrobial |
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How do the stool softeners work? What are they used for? Side effects?
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These drugs work as emollients to soften stool, and allow fluid to enter the stool more easily. These are not acting as cathartics. Indicated for people who should avoid straining to defecate. Fat soluble agents may face impaired absorption.
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How do the osmotic agents work?
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These laxatives draw fluid into the stool. Can be saline based or sugar base, avoid the saline based in pts with electrolyte issues. Can cause abdominal distension and gas. Can be OTC or prescription.
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How do the stimulant laxatives work?
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These drugs actually promote muscle contraction in the colon. Don't use chronically because colonic inertia can result, and you can become dependent on them.
Bisacodyl & senna. Bisacodyl: different onset of action for oral vs rectal |
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How does lubiprostone work? Linaclotide?
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Lubiprostone: use for IBS w/constipation , chronic constipation, opiod induced constipation. Activates chloride channels in GI tract which increases motility and bulking of stool. Classic GI symptoms are side effects, don't use in pregnancy (PGE analouge).
Linaclotide: same indications, act on guanylate cyclase receptors to increase chloride & bicarb secretion and block pain signals. Main side effect is diarrhea |
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What is cholestyramine? How does it work?
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Bile acid binding resin, was indicated for hyperlipidemia. No systemic effects, GI issues, tooth discoloration, malabsorption of fat vitamins.
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What opiod derivatives are used to treat diarrhea?
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Loperamide (Immodium) and diphenoxylate+atropine. Mu receptor agonists that slow intestinal transit. Loperamide has no abuse potential because it doesn't get into the BBB, diphenoxylate + atropine does at high doses (prescription only agent).
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How do clonidine and alosetron act? What are they use
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Clonidine: alpha 2 agonist, reduces sympathetic output. Can cause hypotension, sedation, dry mouth. Prescription only.
Alosetron: serotonin antagonist, use in with with diarrhea IBS. Can cause constipation, possibly ischemic colitis. Need to be a registered provider to dispense. |
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Hypertrophic pyloric stenosis
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More common in males, see recurrent vomiting in first few weeks. Hypertrophy of the pylorus muscle causes obstruction, due to NO deficiency. Can cause metabolic abnormalities due to the vomiting.
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Intussusception
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Most common cause of obstruction in kids, small intestine telescopes into another part. Often due to a lead point from Meckels diverticulum, enlarged lymphoid patch. Presents with abdominal
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Hirschprungs DIsease
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Congential disorder, loss of enteric neurons. Results in dilation proximal and inability to relax the muscle distally. Mostly involves rectum and sigmoid colon. More common in males, present with constipation and abdominal distension. Rectal exam may result in forceful expulsion of stool. Treat with surgery.
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Meckel's DIverticulum
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Most common congenital anamoly of the small intestine. Vitteline duct remains, causing an outpouching. True diverticulum, contains all 3 layers.
2% of population, less than 2 years old 2% will have complications (painless bleeding most common) Males 2:1 2 inches long, within 2 feet of ileocecal valve |
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Omphalocele & Gastroschisis
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Congenital defects, F=M.
O: intestines, liver, other gastric organs in a pouch, due to defect in the abdominal wall. Associated with cardiac issues, Downs. G: lateral defect in abdominal wall, umbilicus is not in |
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Necrotizing Enterocolitis
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Common but can be fatal, seen in low weight premies. Present with feeding intolerance, ab distension, bloody stool very early on. Imaging shows portal venous gas and air in the abdomen. Treat with breast milk, feeding, and surgery.
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How can we diagnose dysphagia?
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Coughing and choking = oropharyngeal
Sticking food in throat = esophageal If solid food only, think mechanical obstruction. If progressive, think stricture or carcinoma. If intermittent think esophageal ring. If solids and liquids, think a neuromuscular problem. If progressive, think scleroderma. If respiratory symptoms, think achalasia. If chest pain, think diffuse esophageal spasm. |
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Describe the following tests used to assess diarrhea and malabsorption
D-xylose Hydrogen breath test Secretin stimulation Fecal elastase |
D-xylose: sugar that does not get metabolized, given orally then detect in urine or blood. Should see high dose in the urine, lower amounts means small intestine is not functioning. Measure of small intestine function. Can be low to bacteria overgrowth, or poor renal function.
Hydrogen breath test: early peak = small intestine bacterial overgrowth, late peak = lactose intolerance (in colon) Pancreatic insuffiency: secretin stimulation then measure duodenal content to check bi-carb levels, low level means chronic pancreatitis. only in special centers. Fecal elastase level, if low think chronic pancreatitis. |
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K-ras and colon cancer?
How to reduce risk? |
wild type Ras, no mutation = cetuximab
has k-ras mutation = no benefit from the drug risk reduction w/aspirin, estrogen, celcoxib (NSAID), stop smoking |
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Types of screening for colon cancer? Ages to get checkeD?
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Stool tests: cancer only
COlonoscopy: cancer and precancerous polyps 50+ average risk 45+ african american 40+ or 10 yrs younger than Dx for family history Family history = first degree relative <60 or two first degree relatives any age FAP 12 HNPCC 20-25 IBD 8 yrs post UC Dx |
