HY Gastrointestinal Disorders PDF

MEHLMANMEDICAL HY GASTRO  MEHLMANMEDICAL.COM YouTube @mehlmanmedical Instagram @mehlman_medical MEHLMANMEDICAL.COM 2  MEHLMANMEDICAL.COM HY Gastro – by Dr Mike Mehlman...

MEHLMANMEDICAL HY GASTRO  MEHLMANMEDICAL.COM YouTube @mehlmanmedical Instagram @mehlman_medical MEHLMANMEDICAL.COM 2  MEHLMANMEDICAL.COM HY Gastro – by Dr Mike Mehlman Disorders affecting lips/oral cavity for USMLE - Combination of perioral melanosis (fancy word for hyperpigmentation around the lips/mouth) + hamartomatous colonic polyps. Peutz-Jeghers syndrome - USMLE will show image of lips pretty much always, and then they’ll ask for what kind of polyps are seen in the colon (i.e., hyperplastic, tubulovillous, etc.), and the answer is just “hamartomatous.” - Aka hereditary hemorrhagic telangiectasia; autosomal dominant. - NBME loves showing a mouth or fingernail picture of telangiectasias. Osler-Weber-Rendu - Q will give nosebleeds + show you the above pic. There can be high-output cardiac failure due to pulmonary AV fistulae. - GI bleeding can occur leading to anemia. - Triad of iron deficiency anemia + esophageal webs (dysphagia) + angular cheilitis (cracked corners of mouth). Plummer-Vinson syndrome - NBME Q can also mention pica (iron deficiency sign where patient eats clay, starch, or ice), or they can show spoon-shaped nails (koilonychia), which are a sign of severe iron deficiency. MEHLMANMEDICAL.COM 3  MEHLMANMEDICAL.COM - Just know it’s possible. USMLE can mention it on upper lip or forehead, and this somehow confuses students, where they think it has to be on extensors only. Lip psoriasis - Aka canker sore. - Usually appears as very painful lesion, self-resolving lesion on labial mucosa. - Not infective; idiopathic; thought to have very mild autoimmune association; sometimes associated with certain triggers like spicy food. Aphthous ulcer - Vasculitis that causes 5+ days of fever + injected (red) eyes and/or lips/tongue + cervical lymphadenopathy + edema of dorsa of the hands + desquamation of palms/soles (often mentioned as palms/soles “rash,” but not true rash). Kawasaki disease - Students obsess over coronary artery aneurysms as though they’re so HY. They’re not. USMLE basically never mentions them. - Often confused with herpes. Perioral impetigo MEHLMANMEDICAL.COM 4  MEHLMANMEDICAL.COM - If they show you image of young kid in particular with lip lesions, it’s usually impetigo caused by S. aureus or Group A Strep (S. pyogenes). - Can lead to PSGN (if caused by Strep), as discussed in the HY Renal PDF. - Caused by HSV1 or 2. USMLE doesn’t give a fuck about HSV1 being the lips and HSV2 being the genitals. Bunch of nonsense perpetuated by other resources. Herpes labialis - Primary infection presents with fever and regional lymphadenopathy. Recurrences aren’t as severe. - HSV goes latent in sensory nerves. - USMLE will show you above pic and then the answer is “DNA, enveloped, linear.” Sounds nitpicky and low-yield, but it’s one of the viral structures they like asking. Don’t confuse with HepB, which is “DNA, enveloped, circular.” I’ve made lots of YouTube clips on that stuff. - Treat with acyclovir à DNA polymerase inhibitor causing chain termination. HSV resistance to it will be due to altered thymidine kinase. - Caused by Group A Strep. - Causes strawberry tongue / red lips + salmon-pink maculopapular body rash. Scarlet fever - Treatment is penicillin to prevent rheumatic fever (type II HS); can also lead to PSGN (type III HS). I discussed this stuff in the HY Cardio and Renal PDFs. - Caused by Coxsackie A (an RNA virus under picornaviridae). - Causes benign, but contagious, lesions on, you guessed it LOL! – the hands, feet, and mouth. - Usually pediatric, but can present in adults (i.e., daycare workers, parents). Hand-foot-mouth - Don’t confuse with coxsackie B, which can cause dilated cardiomyopathy, diabetes type I, and pleurodynia (latter I discussed in HY Pulm PDF). MEHLMANMEDICAL.COM 5  MEHLMANMEDICAL.COM - Also caused by coxsackie A. - Presents as oropharyngeal vesicles or sores. Herpangina - Can occur with or without hand-foot-mouth. - Caused by measles. - White/blue-ish spots on buccal mucosa. Koplik spots - One of the ways to distinguish measles (rubeola) from rubella (German measles). - The same way you can memorize Koplik spots as unique to measles, you should memorize sub-occipital and post-auricular lymphadenophaty as unique to rubella. - Both measles and rubella have a head-to-toe masculopapular body rash. - Both can present with fever, cough, coryza, conjunctivitis. These findings are non-specific for viral infection; it’s been erroneously attributed to only measles over the years, but I’ve it show up in numerous NBME Qs for a variety of viruses). - Stones within the ducts of the salivary glands. - Stensen duct is the opening of the parotid duct (from parotid gland) into the oral cavity, which is located near the 2nd upper molar bilaterally. Sialolithiaisis - Sometimes a Q can say a patient has pain or inflammation on the buccal mucosa across from the second upper molar, and sialadenitis (inflammation) or sialolithiasis can be an answer. - White-ish, painless, rough patch on lateral tongue. Leukoplakia MEHLMANMEDICAL.COM 6  MEHLMANMEDICAL.COM - Precursor to squamous cell carcinoma of tongue. - Biggest risk factor is smoking / chewing tobacco. - Looks like leukoplakia, but caused by EBV. Oral hairy leukoplakia - Not considered premalignant (no dysplasia on biopsy). - Painless white plaque on palate or tongue that bleeds when scraped. Oropharyngeal candidiasis - Seen in immunocompromised patients, such as AIDS or organ transplant recipients on immunosuppressant agents. - Can be seen in patients with asthma who use inhaled corticosteroids. Patients need to rinse their mouths with water after use to ¯ candida risk. - Tx with nystatin mouthwash. - Odynophagia (painful swallowing) in an immunocompromised patient is Candidal esophagitis until proven otherwise. Salivary gland neoplasia - The answer on USMLE for benign salivary gland tumor that has variability in cell size and shape. Pleomorphic adenoma - Most common salivary gland tumor; benign. - Pleomorphic = cells and nuclei have variability in size and shape. - The answer on USMLE for a salivary gland tumor that invades / has spread / if the patient has B-symptoms (fever, night sweats, weight loss). Mucoepidermoid carcinoma - Most common malignant salivary gland tumor. - Malignant means capable of invading, whereas pleomorphic adenoma will not invade. - The answer on USMLE for salivary gland tumor where they say anything about it resembling lymphatic tissue. Warthin tumor - Salivary gland tumor that has lymphoid stroma (i.e., looks like lymphatic tissue). MEHLMANMEDICAL.COM 7  MEHLMANMEDICAL.COM HY Esophageal conditions for USMLE - Herniation of the stomach upward through the diaphragm. - 95% of the time, hiatal hernia is known as “sliding,” where the cardia of the stomach rises upward through the esophageal hiatus (opening in diaphragm where esophagus passes). - “Abnormal relation of the cardia to the lower end of the diaphragm” is answer on NBME. - 5% of the time, it is paraesophageal, where the fundus of the stomach herniates upward through a hole in the diaphragm adjacent the esophagus. - “Protrusion of the fundus into the chest above the level of T10” = answer for paraesophageal hernia on NBME. Hiatal hernia - Often associated with gastroesophageal reflux disease (GERD). - Surgery usually not indicated. - Diagnose with upper endoscopy (asked on 2CK Surg). - Irritation of esophageal mucosa by gastric acid; usually caused by ¯ lower esophageal sphincter (LES) tone. - USMLE wants you to know obesity is a risk factor for GERD, likely due to ­ stretching and pressure applied to the LES. - As mentioned above, hiatal hernia is also a risk factor. - Classic presentation is burning in the throat/chest after eating a meal. - Can present with nocturnal cough or recurrent pneumonitis. These are HY findings in patients who don’t have classic esophageal irritation symptoms. - Can lead to Barrett esophagus (discussed below), which leads to esophageal Gastroesophageal reflux adenocarcinoma. disease (GERD) - First step in diagnosis is 2-week trial of proton pump inhibitor (PPI), such as omeprazole, which will ¯ symptoms. - PPIs are more efficacious than H2-blockers (e.g., cimetidine). If you see both a PPI and H2-blocker as answers for a GERD Q, choose the PPI. - One 2CK Surg form has “2-week trial of H2-blocker” as an answer, but PPI isn’t listed, so just know the Q is out there. - If trial of PPI doesn’t work, 24-hour esophageal pH monitoring is the answer. - Nissen fundoplication is used last resort, but is asked on NBMEs. MEHLMANMEDICAL.COM 8  MEHLMANMEDICAL.COM - Answer can be written as “fundoplication” alone in patient with severe GERD. This also shows up on Peds, where they say infant with severe GERD and fundoplication is answer. - Pediatric GERD will present as coughing up milk 2-3x daily. It will not be described as high-energy or forceful (i.e., pyloric stenosis); it will not be bilious (i.e., duodenal atresia; annular pancreas); it will not occur as choking or spitting up during the first feed (i.e., tracheoesophageal fistula). - Answer to pediatric GERD Q is “immature lower esophageal sphincter”. It’s not complicated, but I’ve seen students say, “Wait, you can get GERD in kids?” - Tx for Peds GERD is thickened feeds (addition of dry rice to formula) and positional change prior to any use of PPIs. - Metaplasia of distal esophagus characterized by conversion of non- keratinized stratified squamous epithelium into columnar epithelium with goblet cells (which secrete mucous). - You’ll sometimes here the latter described as “intestinal columnar epithelium.” This is because the stomach doesn’t have goblet cells; it has mucous neck (foveolar) cells. - Major risk factor for esophageal adenocarcinoma. Barrett esophagus MEHLMANMEDICAL.COM 9  MEHLMANMEDICAL.COM - Can appear grossly red on upper endoscopy. Once visualized, the next best step is biopsy to confirm the presence of Barrett metaplasia. - Affects lower 1/3 of esophagus. - HY pathogenesis is: GERD à Barrett esophagus à adenocarcinoma. - Will present in patient over 50 who has Hx of GERD with either 1) new-onset dysphagia to solids, or 2) dysphagia to solids that progresses to solids and liquids. - The “new-onset dysphagia” can refer to 3-6-month Hx in patient with, e.g., Adenocarcinoma 10-20-year Hx of GERD. - 2CK wants immediate endoscopy in either of the above situations (i.e., don’t choose barium first). - Sometimes rather than making you choose endoscopy straight up, they’ll tell you in the last line an endoscopy was performed and shows a stricture, then they’ll ask for next best step à answer = biopsy of the stricture. - Affects upper 2/3 of esophagus. - Biggest risk factors for USMLE are heavy smoking/alcohol use. - Other risk factors like burns, chemicals, achalasia, etc., are nonsense. - Will present in patient over 50 who is heavy smoker/drinker who has 1) new- Squamous cell carcinoma onset dysphagia to solids, or 2) dysphagia to solids that progresses to solids and liquids. - Same as with adenocarcinoma, USMLE wants immediate endoscopy as the answer, followed by biopsy of a stricture or lesion if present. - Outpouching of esophagus above the cricopharyngeus muscle (just above the upper esophageal sphincter). Zenker diverticulum - Mechanisms on USMLE are numerous and include, “cricopharyngeal muscle spasm” (Surg form 5), “uncoordinated swallowing,” “dysphagia,” and “increased oropharyngeal pressure.” MEHLMANMEDICAL.COM 10  MEHLMANMEDICAL.COM - False diverticulum (contains only mucosa + submucosa; true diverticula, in contrast, such as Meckel, include the muscular layer as well). - Often presents as overweight male over 40-50 with gurgling sounds when swallowing, or regurgitation of undigested food. - Halitosis (bad breath) is buzzy but only mentioned in maybe 1/3 of Qs. - Diagnosis is made with barium swallow. - Treatment on 2CK NBME is “diverticulectomy.” - Tightening (i.e., ­ tone) of the LES due to loss of NO-secreting neurons in the Auerbach (myenteric) plexus. - New NBME wants “enteric ganglia” as the answer for site of problem. - Can be described on NBME as “dilated esophagus with constriction of the gastroesophageal junction.” - Presents usually as dysphagia to both solids and liquids from the start. This is in contrast to cancer, which will be new-onset dysphagia to just solids, or progression from solids only to solids + liquids. The HY point is that neurogenic causes of dysphagia (i.e., achalasia) lead to solids + liquids dysphagia. - Almost always idiopathic; can rarely be caused by Chagas disease. - New 2CK NBME has “South American trypanosomiasis” as the answer for achalasia, which is aka Chagas disease. - First step in diagnosis is barium swallow, which shows a classic “bird’s beak” appearance. Achalasia - After the barium is performed, esophageal manometry (a pressure study) is confirmatory. Biopsy is not traditionally performed. - Treatment is pneumatic (balloon) dilation, followed by myotomy (cutting of muscle fibers of the LES). - As discussed in detail in the HY Pulm PDF, this is an idiopathic autoimmune disease characterized by multi-organ system fibrosis and hardening of tissues (i.e., sclerosis). Systemic Sclerosis - Can lead to GERD. An offline Step 1 NBME wants ¯ LES sphincter tone and ¯ (aka scleroderma) esophageal peristalsis as an answer. This refers to the esophageal dysmotility component of CREST (Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasias). - Can either be iatrogenic (i.e., from endoscopy) or Boerhaave syndrome (from increased pressure due to retching, vomiting, or straining). - USMLE likes to say water-soluble contrast swallow shows accumulation in the mediastinum. If they don’t mention this, they’ll give either recent endoscopy or straining + acutely low BP and high HR, where you have to eliminate the other answers out of reasoning. Esophageal perforation - Water-soluble contrast (Gastrografin) is used in suspected perforation because the contrast will leak into the mediastinum and barium can cause mediastinitis. - In contrast (no pun intended), if patient has aspiration risk, we use barium and not Gastrografin because the latter can cause pneumonitis. - “Esophageal repair” is the Tx on NBME. Pretty straightforward. MEHLMANMEDICAL.COM 11  MEHLMANMEDICAL.COM - Classically retching/vomiting in an alcoholic that causes stretching and tearing of the gastroesophageal junction leading to small amounts of blood in vomitus. Mallory-Weiss tear - Can also occur in patients with eating disorders or hyperemesis gravidarum. - It’s to my observation on NBME material that the highest yield point about MW tear is that it does not cause high-volume hematemesis. If the vignette mentions high-volume blood, that is ruptured varix instead (discussed below). - Enlarged and tortuous superficial esophageal veins due to portal hypertension in patient with cirrhosis or splenic vein thrombosis. Esophageal varices - The mechanism in the setting of cirrhosis: the left gastric vein connects the esophageal veins to the portal vein. In the setting of ­ portal pressure, this pressure backs up to the left gastric vein, which backs up to the esophageal veins. Many USMLE Qs want “left gastric vein” as the answer for the vessel responsible for the varices. - In splenic vein thrombosis, the ­ splenic venous pressure causes formation of collaterals to circumvent the thrombosis. This means nearby veins will form small tributaries/branches from the splenic vein. The left gastric vein is one of them à ­ esophageal venous pressure. - It is to my observation on NBME Qs that 4/5 varices Qs will give a patient with high-volume hematemesis. In contrast, MW tear is ‘just a little blood.” - Ruptured varices are lethal ~50% of the time. The patient will vomit high volumes of blood. - 1/5 Qs might say “just a little blood” if the varix is friable but not overtly ruptured, but the vignette will be obvious (i.e., cirrhosis) + they might just ask for “left gastric vein” as the answer. - Propranolol is prophylaxis, not for acute treatment. - Treatment is endoscopy + banding. - Octreotide can also be used for acute bleeding, but endoscopy + banding is best answer on USMLE if you are forced to choose. - There is a 2CK Q where patient has ¯¯ BP due to ruptured varix and the answer is “IV fluids,” where endoscopy is the wrong answer. I’ve had a student say, “Wait but I thought you said endoscopy and banding is what we MEHLMANMEDICAL.COM 12  MEHLMANMEDICAL.COM do first.” And my response is, yeah, but you always have to address ABCs first on 2CK. They could by all means say patient has O2 sats of 50% and the answer would be give oxygen before fluids. - Idiopathic spasm of the esophagus. - All you need to know is that this that causes pain that can mimic angina pectoris, but patient will be negative for cardiac findings/disease. Diffuse esophageal spasm - Barium shows a corkscrew appearance. - “Nutcracker esophagus” is a similar condition that is due to idiopathic hyperperistalsis and causes pain similar to DES. - Idiopathic allergic condition of the esophagus that presents with difficulty swallowing. - Biopsy shows eosinophils in epithelium (it’s like no shit). Eosinophilic esophagitis - Endoscopy shows “trachealization” of the esophagus with concentric rings. - Patient might have history of asthma or atopy. - Garbage diagnosis for USMLE. Doesn’t exist. Mentioning it here as a negative for USMLE giving a fuck cuz otherwise someone will be like, “Mike u didn’t mention Schatzki ring.” Schatzki ring - Technically a narrowing of the distal esophagus that could be considered as a differential alongside achalasia. Once again, never seen this assessed as a correct answer on any NBME material. Maybe just once as a distractor. Garbage diagnosis. MEHLMANMEDICAL.COM 13  MEHLMANMEDICAL.COM HY GI exocrine hormones quick review - Exocrine means secreted across epithelium into the GI tract. In contrast, endocrine means into the blood. - Produced by “neuroendocrine cells of the small bowel.” - Does 3 things: 1) Causes gall bladder contraction; 2) Causes relaxation of sphincter of Oddi; 3) ­ exocrine pancreas secretion of proteases and lipases into the duodenum. - Impetus for secretion is macronutrients (i.e., fat, protein, carbs) entering the duodenum from the pylorus, although fats are classically the major stimulator. - Even though in theory acid can lead to ­ secretion of CCK, this is wrong on Cholecystokinin (CCK) USMLE. It is macronutrients that cause ­ CCK release on USMLE. - Answer on USMLE for the hormone that is responsible for pain in biliary colic (gallbladder pain from cholelithiasis, where a stone transiently obstructs entrance into the cystic duct during gallbladder contraction). - Step 1 NBME Q will give you pain from biliary colic after patient eats a fatty meal, and then they’ll ask for where the hormone responsible is secreted à answer = “neuroendocrine cells of small bowel.” - Produced by S cells of the duodenum, but USMLE doesn’t give a fuck. - What they care about is that secretin causes ­ bicarb release from the exocrine pancreas into the duodenum, and that stomach acid entering the Secretin duodenum from the pylorus is the impetus for secretion. - What USMLE will do is show you a line graph representing pancreatic secretions, where you can see there’s ­ bicarb release but no ­ in proteases and lipases, and the answer is just “secretin.” - Produced by enterochromaffin-like cells of the GI tract. Weird name, but just deal with it. “Regular enterochromaffin” cells secrete serotonin in the GI tract. - Binds to H2 receptors on parietal cells, stimulating acid secretion. - Enterochromaffin-like cell hyperplasia occurs in chronic gastritis (on NBME); Histamine this makes sense, since we have atrophy or destruction of parietal cells in chronic gastritis, meaning histamine production goes ­ to compensate. - Cimetidine is HY H2-blocker that ¯ stomach acid secretion; can cause gynecomastia. It also inhibits P-450 (­ serum levels of other drugs). Ranitidine does not inhibit P-450. - Secreted by G cells. - ­ acid via two main mechanisms: 1) directly agonizes gastrin receptors on parietal cells; 2) stimulates enterochromaffin-like cells to secrete histamine, Gastrin which in turn ­ stomach acid. - Gastrin levels rise in chronic gastritis and H. pylori infections. - Gastrinoma (aka Zollinger-Ellison syndrome) causes recurrent duodenal ulcers and sometimes jejunal or ileal ulcers; can be part of MEN 1. - Causes ­ water content / volume of pancreatic secretions. - I’d say VIP is the highest yield GI hormone on 2CK Surg forms. VIPoma shows up everywhere. - ~2/3 of Qs will be WDHA syndrome à Watery Diarrhea, Hypokalemia, Vasoactive intestinal Achlorhydria (­ serum pH + low serum Cl-). peptide (VIP) - ~1/3 of Qs will be nothing about diarrhea, but will mention ­ serum pH + low K+ + facial flushing. A 2CK NBME Q gives pH of 7.56 and potassium in the 2s + facial flushing. - USMLE will show graph of a hormone that causes ­ volume of pancreatic secretions but pH and enzyme concentrations don’t ­ à answer = VIP. - Stimulates peristalsis in the absence of food. - Responsible for borborygmi (GI sounds). Motilin - Erythromycin (yes, the antibiotic) can agonize motilin receptors in patients with gastroparesis. Glucose-dependent - Aka gastric inhibitory peptide (GIP). USMLE loves this hormone. insulinotropic peptide - Causes ­ insulin release in response to oral macronutrients (not just carbs). MEHLMANMEDICAL.COM 14  MEHLMANMEDICAL.COM - What you need to know is that it is GIP that is responsible for oral glucse being utilized faster than IV glucose, since we get ­ insulin spike if oral. USMLE will ask this two ways: 1) Two people both get 50g of glucose. One gets it orally. One gets it IV. The one who gets it orally utilizes it faster. Why? à answer = “glucose-dependent insulinotropic peptide.” 2) Two people get 50g IV glucose. One also gets a small amount of oral fatty acids at the same time. The latter person utilizes the IV glucose faster. Why? à answer = “glucose-dependent insulinotropic peptide.” HY GI enzymes quick review - Secreted by both salivary glands and the pancreas to digest starch into monosaccharides. - Pancreatic amylase is ­ in acute pancreatitis. The weird detail I can communicate is Amylase that even though it’s not as reliable or specific as lipase for pancreatitis, various 2CK NBME Qs will give only isolated ­ amylase in some Qs, without even listing lipase. So if you get a Q where amylase is high and lipase isn’t listed, don’t be confused. It’s still pancreatitis. - Secreted by both salivary glands (lingual lipase) and pancreas to break down fats. Lipase - ­ in pancreatitis. - Secreted by chief cells of gastric mucosa. Pepsin - Secreted as pepsinogen, which is a zymogen (means pro-enzyme that is inactive). - Converted into active pepsin by stomach acid, which then breaks down protein. - Secreted by parietal cells (in addition to acid). Intrinsic factor - Binds vitamin B12 and enables its absorption at the terminal ileum. - ¯ in gastrectomy and pernicious anemia (discussed later). - Secreted by exocrine pancreatic acinar cells as the zymogen trypsinogen. - Converted by enterokinase at the brush border into trypsin. - Trypsin is a protease that breaks down protein. - Once active trypsin is formed, it activates other zymogens (e.g., chymotrypsinogen) Trypsin into active proteases. - USMLE will ask about enterokinase, followed by wanting you to know that once we’ve got active trypsin, it is the latter that now activates other things. Enterokinase merely gets things started. Enterokinase - Brush border enzyme that converts trypsinogen from the pancreas into trypsin. - 90% of serotonin is made in the GI tract by enterochromaffin cells. - Metoclopramide is an anti-emetic + prokinetic agent (means ­ peristalsis). It is a D2 antagonist but also an antagonist of serotonin 5HT3 and agonist of 5HT4 receptors. The effects on serotonin receptors ­ gut peristalsis. - Serotonin is also produced by carcinoid tumors, which are neuroendocrine tumors of small bowel or appendix that are S-100 (+) and consist of small blue cells. Serotonin - Carcinoid syndrome will present as flushing, tachycardia, diaphoresis, and diarrhea. Tricuspid regurg can also be seen. - Diagnose with urinary 5-hydroxyindole acetic acid (5-HIAA). - Don’t confuse with serotonin syndrome, which is a drug interaction (e.g., starting a monoamine oxidase inhibitor too soon after discontinuing an SSRI, or if a patient takes St John wort with an SSRI). - Glucagon-like peptide 1. GLP-1 - Stimulates insulin secretion. - Exenatide + liraglutide are GLP-1 receptor agonists for type II diabetes. - Dipeptidyl-peptidase 4. DPP-4 - Breaks down GLP-1. - Therefore, DPP-4 inhibitors ­ GLP-1 and ­ insulin release. MEHLMANMEDICAL.COM 15  MEHLMANMEDICAL.COM - NBME asks which drug listed ­ insulin release (i.e., is an insulin secretagogue); answer = linagliptin (DPP-4 inhibitor). HY GI endocrine hormones quick review - Produced by b-islet cells in the tail of pancreas. - ¯ blood glucose by two main mechanisms: 1) ­ GLUT-4 on skeletal muscle and adipose tissue; 2) ­ glucokinase activity in the liver (hexokinase equivalent at liver), which pulls glucose out of the blood to be stored as glycogen. - ­ Fatty acid and protein synthesis. Also ­ lipoprotein lipase activity (fat storage). - Causes dephosphorylation of enzymes (I talk about this in detail in my HY Biochem pdf). - Insulin secretion is HY: glucose enters b-islet cells via GLUT-2 à ­ ATP production within b-islet cell à closure of ATP-gated K+ channel on membrane of b-islet cell à K+ builds up inside the cell à more positive charge in cell à depolarization of cell à causes Ca2+ to move into cell à triggers insulin vesicle efflux from cell. - Insulin is normally produced as pro-peptide that must have C-peptide cleaved off as part of the process. C-peptide and insulin are co-secreted, meaning their serum levels should match one another. If patient has ­ insulin but ¯ C-peptide, answer = exogenous injection. Insulin If C-peptide is normal/high, insulin production is endogenous. First step is checking serum hypoglycemic levels (“serum hypoglycemic” = type II diabetes med that ¯ glucose, such as sulfonylureas and meglitinides). If serum hypoglycemics are negative, then do CT of abdomen to check for insulinoma. - Insulinoma (and ­ insulin in general) cause Whipple triad: 1) hypoglycemia; 2) symptoms of hypoglycemia (tachycardia, tremulousness); 3) improves with a meal / gets worse between meals. - Insulin is absent in type I diabetes and ­­ in early type-II diabetes (i.e., hyperinsulinemia). - Insulin inhibits ketone formation, so we have ¯ ketones in type II, but ­ ketones in type I. - Hyperinsulinemia causes anovulation / polycystic ovarian syndrome (see my Repro PDF). - USMLE can show you pic of acanthosis nigricans, which is almost always due to insulin resistance. - Patients with chronic pancreatitis and pancreatectomy can have diabetes (loss of pancreatic tail). - Secreted by a-cells of the pancreatic tail. - Causes ­ serum glucose and phosphorylation of enzymes. - Glucagonoma will present as ­ serum glucose and a body rash called necrolytic migratory erythema. Don’t confuse with the facial flushing seen with VIPoma; in addition, VIPoma doesn’t ­ glucose levels. - Patients who receive insulin for diabetes can sometimes have prolonged or exaggerated hypoglycemic effects. If this occurs, an answer for why this occurs on USMLE is “lack of Glucagon counter-regulatory glucagon.” Sounds weird, but it shows up more than once on NBMEs. Essentially, patients with diabetes, or chronic pancreatitis, or pancreatectomy and not just prone to losing the b-islet cells, but they can also lose the a-cells. When glucose goes ¯, glucagon should go ­ to compensate, but if this can’t happen, glucose stays low. - Question on NBME with chronic pancreatitis (chronic burnout from repeated acute pancreatitis; discussed more later) wants you to know that the arrows are: ¯ insulin production, ¯ glucagon production, no-change peripheral response to insulin. - Secreted by delta-cells of pancreatic tail. - ¯ secretion of most GI hormones, as well as growth hormone. Somatostatin - Somatostatinoma presents as steatorrhea (probably due to ¯ pancreatic lipase secretion). - Octreotide is a somatostatin analogue that can be used in addition to endoscopic banding for esophageal varices Tx à leads to ¯ portal blood flow/pressure. - Produced by enteroendocrine cells of GI tract. Ghrelin - All you need to know is that this hormone makes you feel hungry. MEHLMANMEDICAL.COM 16  MEHLMANMEDICAL.COM - Blood levels are highest just at the start of the meal. USMLE will show you a graph of ghrelin levels, and they ask where on the graph corresponds to the start of a meal, and the answer is at the peak. Not complicated. But I’ve seen innumerable students get this wrong. - Produced mostly by adipocytes. - Makes you feel full (i.e., opposite of ghrelin). Leptin - Also plays important role in hypothalamic/anterior pituitary secretion of gonadotropins. - Leptin is ¯ in those with low BMI/anorexia à ¯ GnRH à ¯ LH + ¯ FSH à amenorrhea. Intestinal monosaccharide transport - GLUT transporters allow for movement via facilitated diffusion, where the sugars move down their concentration gradients (i.e., from high to low). - SGLT-1 functions via secondary active transport, where a Na/K ATP-ase on the basolateral membrane pumps Na out of the enterocyte into the blood. This lowers Na within the enterocyte, creating a favorable high-to-low gradient for Na from the intestinal lumen into the cell. This gradient then drives the movement of glucose and galactose against their concentration gradients into the cell, allowing for more efficient absorption. Peptic ulcers HY causes - “Peptic ulcer” is an umbrella term that refers to both duodenal and gastric ulcers. - Gastric ulcers cause pain immediately with meals (due to ­ acid secretion). Patients can sometimes lose weight due to aversion to pain from eating. - Duodenal ulcers cause pain 1-2 hours after meals (due to ­ acid entering duodenum). With meals, the pylorus tightens, thereby relieving any residual discomfort. Patients may gain weight since eating ¯ pain. - Responsible for almost all duodenal ulcers (>95%), whereas it causes a lower % (only >60%) of gastric ulcers. This is merely because the latter are caused by many other things as well, so we simply have ¯ fraction caused by H. pylori. In other words, there’s no special tropism of H. pylori toward duodenal over gastric mucosa. Helicobacter pylori - Mechanism for ulcers that shows up on USMLE is: “secretes proteinaceous substrates that damage mucosal lining.” This is correct over “­ gastric acid secretion” if both are listed side-by-side, even though H. pylori does ­ gastrin levels, which ­ acid secretion. MEHLMANMEDICAL.COM 17  MEHLMANMEDICAL.COM - Produces urease, which causes ­ ammonia production around the organism, allowing it to survive in the ¯ pH of the stomach. - Antral/pyloric ulcers can lead to gastric outlet obstruction. They will mention this in a Surg Q as a “succussion splash.” - ­ risk of MALT lymphoma, a type of B-cell lymphoma. - Diagnose H. pylori with urease breath test or stool antigen. - Treat H. pylori with CAP à clarithromycin, amoxicillin, PPI (e.g., omeprazole). - USMLE really doesn’t give a fuck about the treatment, but CAP is safe to know. Metronidazole, tetracycline, bismuth, and PPI tetrad is used if CAP fails (students ask about those other drugs). - Perforated duodenal ulcer will present as sudden-onset rigid abdomen (involuntary guarding). Patient will often have SIRS, with abnormal vitals due to sympathetic activation. USMLE wants “X-rays of the chest and abdomen” to look for air under the diaphragm (HY finding that indicates ruptured viscus). - Zollinger-Ellison syndrome causes recurrent duodenal ulcers and sometimes jejunal or ileal ulcers. - Can be part of MEN1 or idiopathic. - H. pylori is more common than gastrinoma. As mentioned above, >95% of duodenal ulcers are due to H. pylori. There is an NBME Q where they give older male with a Gastrinoma duodenal ulcer + no other information + they ask for most likely cause à answer = testing for H. pylori; gastrinoma is wrong. - Vignettes can be tricky with gastrinoma and tell you the patient has 8-10 watery stools daily, where you say, “That sounds like VIPoma.” But they’ll also tell you the patient has history of abdo pain after meals. Q on IM form 8 does this as example. - Cause gastric ulcers. I haven’t seen these cause duodenal ulcers on USMLE. - Prostaglandins are necessary for stimulation of gastric alkaline mucous production and maintenance of the gastric lining. NSAIDs à ¯ prostaglandin production à NSAIDs disruption of gastric lining. This can lead to both ulcers and irritation (gastritis). - USMLE wants you to know that PPIs are first-line for ulcer treatment in general, but that misoprostol is a PGE1 analogue that is used in NSAID-induced ulcers (i.e., we’re replenishing the ¯ prostaglandin from NSAIDs). - Rare, but just know they exist. - Called Curling ulcers (think: curling irons are hot). Burns - Loss of fluid post-burns from evaporation à ¯ blood flow to stomach à ischemic ulcers. - Rare, but just know they exist. - Head trauma or brain tumor à ­ intracranial pressure à ­ parasympathetic outflow to stomach à ­ ACh binding to muscarinic receptors at parietal cells à ­ acid production. Head trauma - Don’t forget that the 3 synergistic mechanism for acid production are 1) gastrin binding directly to gastrin receptors on parietal cells; 2) gastrin stimulating enterochromaffin-like cells to secrete histamine, which then binds to H2 receptors on parietal cells; and 3) direct parasympathetic activity, where ACh binds to muscarinic receptors on parietal cells. - Not tested as overt causes of ulcers on USMLE. But you should know that smoking Smoking/Alcohol and alcohol are believed to decrease healing of pre-existing ulcers. MEHLMANMEDICAL.COM 18  MEHLMANMEDICAL.COM Gastritis causes + HY points - Acute gastritis will present as irritation leading to bleeding of gastric mucosa (e.g., from NSAIDs). - Chronic gastritis will be an atrophy or autoimmune destruction of the mucosa associated with ¯ mucosal thickness, ¯ HCl production (achlorhydria), ­ gastrin production, and enterchromaffin-like cell hyperplasia (­ histamine production to compensate for ¯ acid). NBME will give you this constellation of findings and then just simply have “chronic gastritis” as the answer, with acute gastritis not even listed. It’s not hard, but I’ve seen students miss this a lot. - Causes what is referred to as “Type B gastritis,” which is inflammation tending to affect the antrum of the stomach. H. pylori - Can lead to pyloric channel ulcers + gastric outlet obstruction. This will present on 2CK Surg forms as a “succussion splash.” - Causes what’s referred to as type A gastritis,” which affects mostly the fundus/body of the stomach. - Autoimmune antibody-mediated destruction of parietal cells. - Sometimes antibodies can be against intrinsic factor. - Ultra-HY cause of B12 deficiency (­ MCV + hypersegmented neutrophils +/- neuropathy) on USMLE. - Associated with other autoimmune diseases, e.g., vitiligo. So if they give you ­ MCV in patient with, e.g., type I diabetes, you should think, “Autoimmune diseases go together, so if the patient has one AA disease, he/she has ­ propensity for others.” Don’t worry about strict HLA associations here. Pernicious anemia - There is Q on an NBME exam where they ask you to identify the parietal cell. Histo overall is LY for Step 1, but they want you to know that parietal cells are the “midway” cells between the gastric surface superficially and the deeper, basophilic chief cells. Notice how the parietal cells are slightly lighter/more eosinophilic (pink) in comparison to the chief cells, which are darker/more basophilic (purple). - Answer on USMLE for GI bleeding in someone taking, e.g., indomethacin or naproxen. - Causes type A gastritis, affecting the fundus/body. USMLE doesn’t specifically give a fuck, but you should basically be like, “H. pylori causes antral gastritis, whereas other causes like NSAIDs and pernicious anemia are fundus/body of stomach.” NSAIDs - Prostaglandins are necessary for stimulation of gastric alkaline mucous production and maintenance of the gastric lining. NSAIDs à ¯ prostaglandin production à disruption of gastric lining. This can lead to both gastritis (inflammation) and ulcers. - As mentioned above for ulcers, misoprostol can be used in these patients following PPI. MEHLMANMEDICAL.COM 19  MEHLMANMEDICAL.COM Gastric cancer points - Perpetuated over the years as “intestinal vs diffuse” types. USMLE doesn’t care. What you need to know is that histo will show signet-ring cells that contain mucin. And you don’t need to know the histo for this either. - Grossly, can cause a linitis plastica, which is a leather bottle appearance to the stomach. - Gastric metastases can spread hematogenously to the ovaries. These will show up as bilateral ovarian lesions that show, you guessed it, signet-ring cells that contain mucin. - ­ incidence of gastric cancer in Japan due to ­ nitrosamines/smoked foods. - MALT lymphoma is a B cell lymphoma that can be caused by H. pylori. This does not have signet ring cells. - Acanthosis nigricans can be associated with gastric cancer (even though most of the time, it just means insulin resistance). - Virchow node (Troisier sign) à palpable supraclavicular lymph node that can reflect visceral malignancy, especially gastric cancer. Hyperbilirubinemia - Bilirubin is produced from breakdown of heme from RBCs at the spleen. It will initially be “unconjugated” in this form, where it merely leaves the spleen non-covalently bound to albumin and is not water-soluble – i.e., it won’t show up in the urine. Unconjugated bilirubin is aka indirect bilirubin. - In the setting of hemolysis or ­ RBC turnover (i.e., sickle cell, hereditary spherocytosis, blood given during surgery), where we have ­ RBC breakdown, we get ­ indirect bilirubin. - Once it arrives at the liver, it is taken up by the liver and conjugated to glucuronide, making it water-soluble. Conjugated bilirubin is aka direct bilirubin. - If the there’s a problem with uptake at the liver (i.e., acute hepatitis), or there is deficient Unconjugated conjugation enzyme (Gilbert syndrome, Crigler-Najjar), indirect bilirubin also goes ­. (indirect) - Hemolysis or ­ RBC turnover can cause direct bilirubin to go ­ sometimes as well, but the shift will be more toward indirect being ­. I point this out because students often get confused by this, but if we have ­ indirect bilirubin going into the liver, then this means ­ direct bilirubin going out. A 2CK NBME Q gives 9 packs of RBCs given during surgery à days later, total bilirubin is 5.0 and direct bilirubin 2.3 à answer = “overproduction of bilirubin.” - In regard to neonatal labs (i.e., first month of life), I should note that hematocrit % can be in the 50s (NR 45-61; in adults, NR is 40-50). 2CK, for instance, will often show Hct as 56% in a newborn and the student is like “Wow that’s high!” where they think there’s neonatal polycythemia or some other pathology, but it’s actually normal. Unconjugated jaundice can occur in neonates because of ­ RBC turnover where HbF is replaced with HbA. - Direct bilirubin, since it is water-soluble, shows up in the urine. It will also be secreted into bile. Therefore, if we have a bile duct obstruction, we get ­ direct bilirubin. ALP also goes ­ in bile duct obstruction because it is secreted by bile duct epithelium. This means “­ ALP + ­ direct bilirubin” is very buzzy for bile duct obstruction. If ALP is high but direct bilirubin not ­, this can be due to things like bone fractures or Paget disease. - GGT will also go up with bile duct obstruction, since it is also secreted by bile duct epithelium, but USMLE actually rarely mentions this one. What they want you to know is Conjugated GGT spikes with acute alcohol consumption / binge drinking. (direct) - In the event of bile duct obstruction, not only will ALP and direct bilirubin go ­, but the urine becomes darker from ­ direct bilirubin in it (and urobilin, which comes from direct bilirubin, but USMLE doesn’t assess this). In addition, stools become lighter/pale (aka “acholic stools”), since there is ¯ direct bilirubin making it to the intestines, which means ¯ stercobilin production (pigmentation in stool). In other words, “dark urine + pale stools” is buzzy for bile duct obstruction the same way “­ ALP and ­ direct bilirubin” is. - Acute hepatitis can also cause ­ direct bilirubin due to ¯ secretion into bile, in addition to ­ indirect. But this makes sense, since it is literally an intra-hepatic pathology. MEHLMANMEDICAL.COM 20  MEHLMANMEDICAL.COM - Highest yield cause of ­­ direct bilirubin on USMLE is biliary atresia in neonates (discussed later). This is all over the place, whereas Crigler-Najjar (­­ indirect bilirubin in neonates) is nonexistent. - Dubin-Johnson and Rotor syndromes are virtually nonexistent on USMLE but cause ­ direct bilirubin in adults due to ¯ bile excretory pumps at the liver. Students get hysterical about these because they sound weird, but they’re LY. Dubin-Johnson is asked once on a new 2CK NBME form. But apart from that, LY. - Cholangitis (inflammation of bile ducts), choledocholithiasis (stone in biliary tree), choledochal cyst, head of pancreas cancer (impingement on common bile duct), and cholangiocarcinoma (bile duct cancer) are all HY causes of bile duct obstruction. I discuss all of these conditions in detail below. Bilirubin uptake/secretion diseases - Pronounced “Jeel-BEAR, not “GILL-burt.” Gastroenterologist I met once tripped out over med students pronouncing this wrong. - Partial deficiency of bilirubin uptake enzyme at the liver (UDP glucuronosyltransferase). Gilbert - Presents as isolated ­ indirect bilirubin with yellow eyes in young adult with stress factor, such as studying for exams, or recent surgery/trauma. The patient will otherwise be completely healthy. - No treatment necessary. - Near-absence of UDP-glucuronosyltransferase causing ­­ indirect bilirubin in neonate. Crigler-Najjar - Nonexistent yieldness but students ask about this. - ¯ excretion of bilirubin into bile at the liver due to ¯ secretory pumps. - Causes ­ direct bilirubin in otherwise healthy adult. Dubin-Johnson - Can cause black liver in theory. - Asked once on new 2CK NBME. Apart from that, nonexistent on USMLE material. - Same as Dubin-Johnson but no black liver. - Nonexistent diagnosis on USMLE. Students get maniacal over this supposedly not Rotor having a black liver, whereas Dubin-Johnson has a black liver – “Rotor! That’s the one that has no black liver but Dubin-Johnson does!” Relax. Take two steps back, chill the fuck out for two seconds. USMLE doesn’t give a fuck. - One of the highest yield Peds diagnoses. Answer on USMLE for ­­ direct bilirubin in a kid under the age of 6 weeks. Biliary atresia - Caused by lack of development of the intrahepatic bile ductules and biliary tree. - Ultrasound will be done first, but USMLE wants liver biopsy to confirm the diagnosis. - Kasai procedure is done to treat, followed by liver transplant if unsuccessful. Autoimmune liver conditions - Inflammation of bile ducts within the liver, leading to their destruction. - Answer in a woman 20s-50s who has generalized pruritis, ­ serum cholesterol, ­ ALP, ­ direct bilirubin. - USMLE loves to mention Hx of autoimmune disease in the patient or family member (because autoimmune diseases go together). So they’ll say she has type I diabetes mellitus, SLE, or vitiligo; or her brother has RA, etc. Primary biliary cirrhosis - They can mention a stone is present in the gallbladder on ultrasound, which gets some students real emotional / confused, but it makes sense since patient has ­ cholesterol. It’s just a distractor point and doesn’t relate to the actual diagnosis at hand. - Diagnose with anti-mitochondrial antibodies as first step, followed by liver biopsy to confirm. MEHLMANMEDICAL.COM 21  MEHLMANMEDICAL.COM - Initial Tx = ursodeoxycholic acid (ursodiol). - New NBME material for Step 1 asks a couple Qs on fat-soluble vitamin malabsorption for PBC (deficiency of A and D on NBME for each Q, respectively, with no info supporting those presentations; they just ask for hypothetical vitamin deficiency). In theory, would be due to biliary obstruction, where ¯ bile entering small bowel merely means ¯ fat absorption. This is nothing special to PBC, but I mention it because it’s asked twice. Autoimmune hepatitis - Young adult with ­ LFTs who has (+) anti-smooth muscle antibodies. HY Hepatobiliary conditions - Head of pancreas cancer impinges on common bile duct, resulting in obstructive jaundice (­ ALP + ­ direct bilirubin) in smoker with weight loss, or in patient who had gallbladder taken out years ago (so it clearly can’t be due to a stone in common bile duct). - Patient will not be febrile; can have dull abdominal pain. - Courvoisier sign is a painless, palpable gallbladder in an afebrile patient who’s jaundiced. This is pancreatic cancer until proven otherwise and is Pancreatic cancer pass-level. - Pancreatic enzymes are normal in pancreatic cancer. - USMLE wants CT of the abdomen to diagnose. - Whipple procedure is done to remove head of pancreas. If the cancer is isolated to the tail, distal pancreatectomy is the answer. - Patients with pancreatectomy need pancreatic enzyme supplementation. The exam can write this as “pancrelipase.” - Bile duct cancer. Answer on USMLE if the vignette sounds like pancreatic cancer but they tell you in the last line CT is negative. Cholangiocarcinoma - Answer is ERCP as next best step. - Smoking is risk factor, same as pancreatic cancer. - Can be caused by Clonorchis sinensis (trematode). - Stones in the gallbladder. - Presents with biliary colic, which is acute-onset waxing/waning spasm- like pain in the epigastrium or RUQ. - Pain is due to cholecystokinin causing gall bladder contractions, where a stone within the gallbladder transiently obstructs flow of bile into cystic duct. They ask this on 2CK as well, where patient will biliary colic and answer is "obstruction of cystic duct opening by stone." Not dramatic. - Classic demographic is 4Fs = Fat, Forties, Female, Fertile for cholesterol stones. This is because estrogen upregulates HMG-CoA reductase, causing ­ cholesterol synthesis and secretion into bile. NBME will give you standard vignette of 4Fs, and then the answer will just be “increased Cholelithiasis secretion of cholesterol into bile.” - Another NBME Q gives vignette of cholelithiasis, and then rather than asking for the diagnosis, they ask what the patient most likely has à answer = “lithogenic bile.” Slightly awkward, but means promoting the formation of stones. - ­ cholesterol stones in pregnancy not just due to estrogen effect but also because progesterone slows biliary peristalsis (biliary sludging). Tangentially, progesterone also slows ureteral peristalsis, which is why there’s ­ risk of pyelonephritis (as discussed in the HY Renal PDF). - Cholesterol stones most common, but pigment (calcium bilirubinate) stones are exceedingly HY for hereditary spherocytosis and sickle cell, due to ­ RBC turnover. MEHLMANMEDICAL.COM 22  MEHLMANMEDICAL.COM - USMLE wants you to know that splenectomy is Tx for hereditary spherocytosis to ¯ incidence of cholelithiasis. Sometimes the vignette wants “cholecystectomy + splenectomy” as combined Tx. Or if they say this was in a parent’s Hx in patient with low Hb, you know the Dx is hereditary spherocytosis (autosomal dominant). - Infections can also sometimes cause pigment stones, but LY. - Diagnose with abdominal ultrasound. - Ursodeoxycholic acid (ursodiol) ¯ secretion of cholesterol into bile. USMLE just wants you to know this MOA + that it can be used in patients with asymptomatic cholelithiasis, those declining cholecystectomy, and in pregnancy. - Cholelithiasis + fever. - Vignette will sound exactly like cholelithiasis, but if we add a fever on top of it, we now just call it cholecystitis. - Virtually always due to obstruction by a stone + infection as a result. - Diagnose with abdominal ultrasound, showing the stones. - If ultrasound is negative, do a HIDA scan. - Tx is cholecystectomy. - Emphysematous cholecystitis is air visualized within the biliary wall. USMLE wants Clostridium perfringens as the organism (can cause gas gangrene anywhere) in this case. Cholecystitis - Chronic cholecystitis is calcification of the gallbladder (aka chronic calculous cholecystitis, or “porcelain gallbladder”). It is due to repeated bouts of acute cholecystitis. - ALP and bilirubin will not be increased 19/20 questions. This is because inflammation of the gallbladder doesn’t mean we have any form of common bile duct obstruction. However there is one nonsense Q on a 2CK NBME where 4 of the answers are wildly wrong, with correct answer being cholecystitis in setting of high ALP + direct bilirubin. Since cholecystitis is caused by stones virtually always, the implication is patients can occasionally have concurrent choledocholithiasis. - Stone anywhere within the biliary tree. Don’t confuse with cholelithiasis. - Obstructive jaundice (­ ALP + ­ direct bilirubin) in patient who has Hx of cholelithiasis or Hx of cholecystectomy performed within the past week. - Regarding the latter, the Q can say patient had cholecystectomy performed a week ago + “intra-operative cholangiography was not performed.” The implication is bile duct patency is supposed to be visualized during cholecystectomy to ensure there isn’t a stone retained within the biliary tree. However, the Q need not say “intra-operative cholangiography was not performed.” This makes the Q pass-level. Choledocholithiasis - USMLE wants abdominal ultrasound followed by ERCP as the answer. ERCP tends to show up as what they want, but there is a Q floating around somewhere that asks for ultrasound first, so know that sequence. - As I talked about earlier, I’ve never seen MRCP as a correct answer. - Being able to discern choledocholithiasis from pancreatic cancer is vital for USMLE. If they give you obstructive jaundice but say the patient is a heavy smoker with weight loss, or hasn’t had a gallbladder for 25 years, you know it’s head of pancreas cancer, not choledocholithiasis. And then, once again, if it sounds like pancreatic cancer but the CT is negative, that’s cholangiocarcinoma and we do ERCP. - Gallstone pancreatitis is a type of choledocholithiasis in which the stone has descended distally enough in the common bile duct that it now obstructs the hepatopancreatic ampulla. This results in a backflow of Gallstone pancreatitis pancreatic enzymes to the pancreas causing damage à acute pancreatitis. - USMLE wants “hepatopancreatic ampulla” as correct over “common bile duct” if they ask you to choose location of the obstruction. Slightly odd, MEHLMANMEDICAL.COM 23  MEHLMANMEDICAL.COM since the stone is still in the common bile duct, but hepatopancreatic ampulla blockage is why we have the pancreatitis. - Vignette will give obstructive jaundice but also high pancreatic enzymes. - In other words, the Q will give ­ ALP, ­ direct bilirubin, and ­ amylase / lipase. - I repeat that pancreatic cancer will never have elevated enzymes on USMLE, so this is a pass-level means to distinguish. - New 2CK NBME has CT of the abdomen as done first, prior to ERCP. This is because even though we have a stone requiring removal from the biliary tree, CT of the abdomen first looks for pancreatic fluid collection. - Inflammation of the bile ducts. You must know Charcot triad for cholangitis: 1) fever, 2) jaundice, 3) abdominal pain. We classically learn this as “RUQ/epigastric pain,” but I can tell you USMLE doesn’t give a fuck and will just say “abdominal pain.” I’ve had students get cholangitis Qs wrong because they’re like, “I thought it had to be RUQ pain though.” And I’m like, yeah, I agree, but USMLE doesn’t give a fuck. - Will present 3 ways on USMLE: - 2/5 Qs will be ascending cholangitis, which is infection from ascension of bowel flora (E. coli, Bacteroides) up the common bile duct. - 2/5 Qs will be primary sclerosing cholangitis, which is inflammation of the bile ducts in the setting of IBD (always due to ulcerative colitis on USMLE, Cholangitis but can rarely be due to Crohn in real life). p-ANCA can be positive, and there can be a beaded appearance of the common bile duct on cholangiogram. On 2CK NBME 10, there is a Q on primary sclerosing cholangitis where the patient is afebrile (rare; i.e., we don’t have full Charcot triad), but they say patient has UC + obstructive jaundice + ERCP shows “narrowing of the bile ducts,” so the answer is evidently PSC. - 1/5 Qs will just give you a patient with history of cholelithiasis, where the implication is a stone has descended causing choledocholithiasis, which in turn led to obstruction + inflammation of the common bile duct. - USMLE wants antibiotics + ERCP to diagnose and treat. Biliary drainage by ERCP ¯ morbidity and mortality. - ­ amylase and/or lipase in patient who has abdominal pain. - Pain need not radiate to the back. - Alcoholism and stones are two biggest risk factors. - Hyperlipidemia and hypercalcemia can also occasionally be causes. - Can be caused by drugs (didanosine is HIV NRTI; exenatide is a GLP-1 analogue for diabetes). - Scorpion sting and mumps as causes are nonexistent on USMLE. - Can be caused by choledocholithiasis (gallstone pancreatitis; ­ pancreatic enzymes in setting of ­ ALP and ­ direct bilirubin). - Results in enzymatic fat necrosis. - You don’t need to memorize Ranson criteria (elaborate criteria for Surg to determine prognosis in pancreatitis). What you need to know are two Acute pancreatitis main points: 1) ¯ Serum calcium and ­ glucose are bad prognostic indicators. In fact, I’d say low calcium is quite possibly the highest yield variable on USMLE for pancreatitis. There are many long/vague pancreatitis Qs out there, where they’ll mention ¯ calcium in the stem, and you’re like “Boom pancreatitis.” 2) The degree of lipase and/or amylase elevation doesn’t correlate with prognosis. In other words, if amylase is 1200 versus 10,000, that’s not important for patient outcome. 3) The rest of the Ranson criteria is more Surg rotation masturbation info and otherwise nonsense for USMLE. MEHLMANMEDICAL.COM 24  MEHLMANMEDICAL.COM - It’s to my observation NBME Qs will sometimes list high amylase without mentioning lipase for whatever reason. Lipase is more specific for pancreatitis, but it’s what NBME sometimes does, so don’t be confused. - HY initial management for 2CK is a triad: 1) NPO (nil per os; or nothing by mouth; this can be written as simply bowel rest as NBME answer); 2) NG tube decompression; 3) IV fluids with normal saline. This triad is not specific for pancreatitis, and can be done for a number of GI-related conditions, including cholangitis and stones. But it just tends to get tested a lot for pancreatitis. - After this initial triad, “CT scan of the abdomen” is answer on NBME as next best step to look for any degree of fluid collection. If a pancreatic pseudocyst is present, NBME answer is to drain this by ERCP. - It’s to my observation USMLE doesn’t assess antibiotics as part of pancreatitis Tx, but apparently the carbapenems (like imipenem) have fantastic penetration of pancreatic tissue. - A 2CK NBME Q gives pancreatitis + similar image as above, and the answer is just ERCP (for drainage of the pseudocyst within black circle). - A necrosectomy is removal of pancreatic tissue in the setting of high fraction of necrosis. Patients with pancreatectomy require enzyme replacement (pancrelipase). - Acute pancreatitis is HY cause of ARDS. - Steatorrhea in alcoholic or patient with recurrent acute pancreatitis episodes à results in pancreatic burnout with ¯ production of pancreatic enzymes à ¯ proteases/lipases à malabsorption. - In other words, we have normal pancreatic enzymes – i.e., they are not elevated. - Question can say alcoholic has ­ fat and protein seen in stool. - D-xylose test is normal. This is a monosaccharide that is readily absorbed Chronic pancreatitis by the small bowel insofar as the intestinal lining is intact. So if we get steatorrhea + normal D-xylose, this can be due to pancreatic insufficiency or lactose intolerance. If D-xylose test is abnormal, we know the malabsorption is due to an intestinal lining issue, such as Celiac or Crohn. - If the USMLE gives you a CT for chronic pancreatitis, they will show you calcification within the pancreas. MEHLMANMEDICAL.COM 25  MEHLMANMEDICAL.COM - Tx = pancreatic enzyme supplementation (pancrelipase). - The answer on 2CK Surg if they give you patient with cholecystectomy within the past week who now has fever, abdominal pain, and ­ direct bilirubin. Bile duct leak - During the surgical anastomoses created during cholecystectomy, sometimes there can be a post-op bile leak, literally. Weird diagnosis but it shows up on occasion. - The answer on USMLE if the Q sounds like gallstone pancreatitis (i.e., ­ Sphincter of Oddi dysfunction ALP, ­ direct bilirubin, ­ pancreatic enzymes) but the patient hasn’t had a gallbladder for many years (so it can’t be a stone causing the obstruction). - Gallstone enters small bowel and causes an intestinal obstruction. - The answer on USMLE if they say “air in the biliary tree” (pneumobilia). - Can be caused by cholecystoduodenal fistula, which is when a patient with cholelithiasis can develop a conduit between the gallbladder and Gallstone ileus small bowel. - What the USMLE will do is give you a long, rambling paragraph where they say “air in the biliary tree” in the last line. The answer will then just be “gallstone ileus” straight up, or it will be “cholecystoduodenal fistula.” - Asked on 2CK Surg. What they’re going to do is give you a long, nonsense paragraph with ­ ALP and ­ direct bilirubin + they say “CT shows a cystic Choledochal cyst structure within the biliary tree.” Answer = “simple excision of the cyst.” Students are huh, what’s going on here? à choledochal cyst. You have to just excise it. Bullshit/dumb diagnosis. Take it up with NBME not me. - As mentioned earlier, this will be a woman 20s-50s who has generalized pruritis, ­ cholesterol, ­ ALP, ­ direct bilirubin, and Hx of autoimmune disease in her or a relative. Primary biliary cirrhosis - Diagnose with anti-mitochondrial antibodies as first step, followed by liver biopsy to confirm. - Initial Tx = ursodeoxycholic acid (ursodiol). - One of the highest yield diagnoses on 2CK. - Bacterial infection of peritoneal fluid by mixed enteric flora. - The answer on USMLE when they give you diffuse abdominal pain and fever in one of the three following scenarios: 1) cirrhosis; 2) recent peritoneal dialysis; 3) nephrotic syndrome. - Shifting dullness” or a “fluid wave” are buzzy for ascites, but questions Spontaneous bacterial will often omit these descriptors from stems. What they care about is you peritonitis (SBP) identifying when a patient either has a major risk factor for ascites, or are aware of a peritoneal intervention as the cause for the presentation. - In other words, they can tell you a patient has cirrhosis + abdo pain + fever, where they don’t have to mention a fluid wave, but you just have to infer, “Well he/she clearly has major risk factor for ascites, so this sounds like SBP.” MEHLMANMEDICAL.COM 26  MEHLMANMEDICAL.COM - There is a 2CK Peds Q where they say kid with minimal change disease (nephrotic syndrome) has abdo pain + fever à answer = spontaneous bacterial peritonitis. - Next best step in diagnosis is abdominal paracentesis. This refers to aspiration of fluid from the peritoneal cavity. Do not confuse this with pericardiocentesis. “Paracentesis” as an answer shows up everywhere, and I’ve seen students avoid it because they’re like, “What? I thought that meant pericardiocentesis.” - After the paracentesis is done, USMLE wants a very specific order for what to do next. Choose “white cell count and differential” first if it’s listed, followed by “gram stain and culture of the fluid.” - This order is important because “gram stain and culture of the fluid” is a correct answer in one Q but wrong answer in another Q, where “white cell count and differential” is correct to do first. - The reason white cell count and differential is done first is because SBP is diagnosed when paracentesis shows >250 WBCs/µL. - There is a new 2CK Q where they give ascites in patient with cirrhosis, but do not mention fever or abdominal pain. However, they say paracentesis shows 900 WBC//µL à answer = “antibiotic therapy.” It should be made clear though that ~6/7 SBP Qs will give abdo pain and fever. - Treatment is ceftriaxone. - Obscure diagnosis where they tell you adult has an abdominal CT for unrelated reason and has a 1-2-cm hepatic lesion with a central scar. There will be zero mention of trauma or infection. Every student says WTF. Focal nodular hyperplasia - This is a lesion of hepatocellular hyperplasia that does not require treatment. This is the answer on NBME, where they tell you CT shows hepatic lesion with central scar. Answer = “no further diagnostic studies indicated.” HY cirrhosis points - Cirrhosis is a small, shrunken, burnt out liver due to chronic disease. - HY causes are alcoholism, HepB/C, Wilson disease, hemochromatosis, NASH, a1-antitrypsin deficiency etc. - “Burned out” means LFTs are normal or low – i.e., there is not transaminitis as with acute hepatitis. - USMLE likes ­ PT and ¯ clotting factor synthesis in cirrhotic patients. - Hyperammonemia occurs due to ¯ urea cycle activity (normally occurs in liver). This can cause hepatic encephalopathy (confusion) and asterixis (“hepatic flap” of the hands). - USMLE likes acute exacerbations of hyperammonemia caused by GI bleeds à ­ ammonia absorption. - Spontaneous bacterial peritonitis (SBP) is ­­ HY on 2CK, as discussed above. - Esophageal varices from ­ portal pressure that backs up to left gastric vein (discussed earlier). - Caput medusae are visible periumbilical veins (superior epigastric veins). Systemic inflammatory response syndrome (SIRS) - Knowing this short table is vital for understanding many IM and Surg Qs on 2CK. If you’re studying for Step 1, I’d say it’s still worth knowing this. - In the setting of stress (i.e., due to trauma, surgery, autoimmune flare, infection), catecholamines and ­ sympathetic activity might shift the patient’s vitals out of the normal range. - The reason knowing SIRS is important is because the patient can have abnormal vitals without having an infection. - 2 or more of the following: SIRS - Temperature 38 (100.4). - HR >90. MEHLMANMEDICAL.COM 27  MEHLMANMEDICAL.COM - RR >20. - WBCs 12,000. Sepsis - SIRS + source of infection. Septic shock - Sepsis + low BP. - Sometimes you will see a patient’s vitals slightly out of the normal range in the setting of trauma, surgery, or autoimmune flares, and you have to be able to say, “There’s no infection. That’s just SIRS from sympathetic activation.” - Knowing if a patient is septic is important for management of patients on 2CK, where sometimes antibiotic regimens are stepped up. For example, when treating PID, if the patient is septic, intravenous ceftriaxone and azithromycin is correct on one of the 2CK NBMEs; IM ceftriaxone and oral azithromycin is wrong. This is because the latter is for most patients who have PID but aren’t septic. - Ceftriaxone is frequently an answer on 2CK for in-hospital patients who are septic from a variety of community-acquired conditions, e.g., pneumonia, pyelonephritis, prostatitis. For instance, community- acquired pneumonia is empirically treated with azithromycin (on 2CK NBME 8), but if patient is septic, we can go straight to ceftriaxone (have seen this more than once on 2CK NBMEs). - For hospital-acquired infections in which patients are septic, NBME goes hard-hitting with vancomycin PLUS ceftazidime or cefepime. This regimen covers MRSA and Pseudomonas. Miscellaneous 2CK Surgery intestinal diagnoses - One of the highest yield causes of small bowel obstruction (SBO) on USMLE. - Occur as a result of major abdominal surgery – i.e., hysterectomy, laparotomy, appendectomy. - Prior surgery results in inflammation that yields fibrin deposition within the peritoneal cavity. This causes “fibrous adhesions” over time that the small bowel can get caught in. - Vignette will say, e.g., 50-year-old who had laparotomy 10 years ago for gunshot wound now has obstipation (failure to pass flatus in addition to stool) for 2 days + SIRS. This is pass-level and answer is just “adhesions.” - New 2CK NBME has “mechanical obstruction of small intestine” as the answer in patient with Hx of appendectomy. Pass-level, but that’s another way they can write the answer. Adhesions - As mentioned earlier, for many abdo conditions – i.e., SBO, pancreatitis, cholangitis, etc., a general “triad” of NPO, IV fluids, and NG tube is done first. In other words, you might get a simple adhesions Q, and then the answer is just “0.9% saline” as the first step, where bowel rest and NG tube aren’t listed. - If the patient is stable, do abdominal X-ray if SBO is suspected to look for gas / obstruction. If the patient is unstable (i.e., low BP), go straight to laparotomy. Never do a CT scan in an unstable patient on USMLE (this includes patients with normal BP after IV fluids given to restore low BP – i.e., the fluids are just acting as a temporizing measure and you need to find source of problem asap). - Crohn disease can cause intraluminal fibrotic strictures, not adhesions. There is a 2CK Q that lists both as answer choices. Strictures due to Crohn are internal / within the lumen; adhesions are external fibrotic bands. - Surgery is a stressor / form of trauma. Especially post-abdominal surgery in which the bowel has been touched/manipulated, there can be acute diminution of peristalsis resulting in pseudo-obstruction (i.e., the patient is obstipated but there’s no physical obstruction). Post-op ileus - Opioids can ¯ peristalsis / cause constipation. These should be considered as a contributing factor to ileus. An important rule for USMLE is that we always treat pain fully, even if patient has Hx of drug abuse or ileus. There is a 2CK Q where a patient has ileus post-major surgery; answer is “maintain dose of opioids + add stool softeners.” MEHLMANMEDICAL.COM 28  MEHLMANMEDICAL.COM - If the Q gives you Bristol 7 stool (watery diarrhea; no solid pieces) with laxatives but Bristol 1 (severe constipation; pellet-like stools) when on nothing, answer on NBME is “add fiber,” with the aim being Bristol 3-4. - Large bowel pseudo-obstruction. - Classically follows hip surgery for whatever reason. - Think of this as ileus but of the large, not small, bowel. “Ileus” sounds like ileum, Ogilvie syndrome which is part of small bowel. So ileus isn’t used to refer to large bowel pseudo- obstruction. - Abdominal x-ray is what we do first in stable patients when we are looking for suspected obstruction. If patient is unstable, always go straight to laparotomy. - Shows up on 2CK NBME. You just need to know this is the answer for someone who has ¯ hemoglobin + bilious vomiting. Duodenal hematoma - The ¯ Hb is because the patient is bleeding internally. - Bilious vomiting implies obstruction (almost always duodenal). - Ultra-HY on 2CK; caused by Hx of duodenal ulcers. - Highest-yield point is that this is diagnosed with chest and abdominal x-rays showing air under the diaphragm. Presents two ways: 1) Q will give patient who has Hx of abdo pain after meals (implying Hx of duodenal ulcer) + now has SIRS + acutely worse abdo pain + rigid abdomen à answer = “x- Duodenal perforation rays of the chest and abdomen.” 2) Q will say acute-onset epigastric pain as though the patient was kicked in abdomen + board-like rigidity + x-rays show air under the diaphragm à answer = “immediate surgical exploration of upper abdomen.” - Not a hard presentation or management, but it shows up all over the place + students get this wrong all the time. Easy points. - Complication of splenectomy. Shows up on 2CK Surg. Subphrenic abscess - Patient will have fever + abdo pain + leukocytosis post-splenectomy + they’ll ask for diagnosis à answer = subphrenic abscess. Tx = drain. - Answer on 2CK in patient who has diarrhea + hypoglycemia post-major surgery of the stomach/small bowel. Dumping syndrome - Post-gastrectomy, for instance, “rapid transit of hyperosmolar chyme” is an answer on NBME for the mechanism. This triggers a ­­ spike in insulin due to glucose-dependent insulinotropic peptide. - Answer on 2CK in a patient who has diarrhea post-major surgery of the stomach/small bowel without hypoglycemia. The vignettes can otherwise sound pretty similar. Blind loop syndrome - This is when a part of the proximal small bowel forms a crevice or nook in which peristalsis bypasses this “blind” segment, thereby creating stasis within it. This can lead to small intestinal bacterial overgrowth (SIBO) and diarrhea. HY Referred pain Spleen - Splenic laceration à ULQ pain +/- can refer to left shoulder (Kehr sign). - Diaphragmatic irritation can cause pain going to left shoulder (asked on NBME); spleen is Diaphragm wrong answer. The key here is they ask “irritation.” Gallbladder - RUQ or epigastric pain +/- can refer to right shoulder. - Epigastric pain initially (visceral peritoneal inflammation) that migrates to RLQ (parietal Appendix peritoneal inflammation). MEHLMANMEDICAL.COM 29  MEHLMANMEDICAL.COM GI Surgeries for 2CK - There are countless fancy GI surgeries that could be discussed just for the sake of it, but it’s a vehement waste of time. I’m going to comment on just stuff I think is HY for USMLE, without the nonsense. - The Billroth II, or gastrojejunostomy, is a partial gastrectomy that shows up sometimes on Surg forms as causing dumping or blind loop syndromes. - In other words, they’ll say a patient has diarrhea following a Billroth II gastrojejunostomy and then ask for diagnosis à answer = blind loop syndrome. - Or they’ll give diarrhea + hypoglycemia (dumping syndrome), and the answer is just “rapid transit of hyperosmolar chyme.” Gastrectomy - Can cause B12 deficiency due to removal of parietal cells. Can also cause B1 deficiency (asked twice on new 2CK NBMEs) à confusion/nystagmus (i.e., Wernicke findings; B12 deficiency doesn’t present with these); can have (+) Romberg sign in both B1 and B12 deficiency Qs (for B1, this is part of dry beriberi; for B12, this is part of subacute combined degeneration). - Done for gastric cancer and perforations. - In contrast to gastrectomy, no part of the stomach is removed here. A pouch is made where part of the stomach is merely walled off from food passage. - Answer on Family Med forms weirdly enough for the most effective way to manage weight in someone who is morbidly obese, albeit last resort. Not sure why this is on FM forms but they ask it. Gastric bypass - Sequelae same as for gastrectomy. B12 deficiency can occur due to disruption of parietal cells, even though stomach is not removed. - Another name for gastric bypass is roux-en-Y, which will show up tons on 2CK Surg forms as a wrong/distractor answer. I’ve only seen “gastric bypass surgery” as correct on FM forms, but never “roux-en-Y” on Surg forms. - Aka pancreaticoduodenectomy. - Used for head of pancreas cancer. - Because of interconnected blood supply, removal of head of pancreas requires removal of the gall bladder, duodenum, and proximal jejunum. Whipple procedure - As I said, just know that this is done for head of pancreas cancer. Distal pancreatectomy - Answer on Surg form for tail of pancreas cancer. Not complicated, but it’s asked. - Even though segme