1
Q
Hep B
A
• General: most well known virus of the hepadnavirus, its a DNA virus (blues and greens), enveloped virus
◦unique: replicates inside AND outside the nucleus (intranuclear and cytoplasmic); circular genome thats partially dbl stranded (becomes fully dbl
during replication) double stranded (single stranded: parvo)…kumbaya circle
◦Progression of replication: from partially dbl-stranded DNA -> intermediate single-stranded RNA -> dbl progeny DNA
• Transmission (similar to Hep C): through sex, sharing blood products, sharing needles, vertical transmission (mother->child, blood in childbirth; it doesnt
cross placenta, would only get transferred isblood mixes during delivery); healthcare workers at risk via needle sticks (transmission level is low)
• Symptoms: hepatitis (inflammation of the liver), in addition to RUQ pain, jaundice, etc…some acute (go away with time), some chronic (less likely than C;
only 5-10% of adult, younger kids and newborn more likely (90-95% of newborn)
• Extra-hepatic manifestations: prodromal serum-sickness type illness with purpuric rash (non blanching dark macules) and arthralgias, glomerular
nephritis, or polyarthritis nodosa (PAN)-systemic vasculitis of medium/small arteries-small aneurysms that form are said to have a beads on a strong
◦PAN can affect blood vessels leading to the kidney, manifest as: reduced GFR and HTN
◦Other renal dz: membranous glomerulernephritis (thickened glomerular membrane) and membranoproliferative GN (deposits in the mesangium
expanding into the glomerular BM causing a tram-track appearance)
• Liver enzymes and serologies
◦viral hepatitis: elevationin liver enzymes and so does hepatitis form alcohol
◦Alcoholic hepatitis: AST>ALT, viral (acute): ALT>AST…ALT will fall after symptomatic stage is over (may not go back to nml)
◦Serum ALT is nml early in neonatal hepatitis
• Serologies: we’re all one SPECIES
◦red: Hep B surface antigen: HBSAg (marker of active infection [acute or chronic], first one that is clinically measurable)
◦Orange: HBeAg (hep B envelope antigen)-highly correlates with infectivity, if its high, person is usually highly infectious
◦Red S, and orange E are both Ag, havent had enough time to make Ab; timeframe for symptoms
◦Yellow C: Anti-HBc (Hep b core Ab) is positive during the window period-when pt has started to develop anti-Hep B surface Ab so they Ab
have started to bind the Hep B surface Ag and neither of them may be detectable=window pd/false reassurance that person is NOT infected
(BUT: Anti-HBcore Ab will be positive, aka they still have an infection)…recovered ppl will have Anti-HBe or anti-HBcore Ab in addition to Anti-
HBsAb
◦ green E: Anti-HBe=low infectivity
◦Second S, blue: Anti-HBsAb indicates recovery and end of infection (acute and chronic); this is the value checked for anyone who has been
immunized, they will check positive for this)
• Tx: acute cases clear up by themselves, pregnant women and ppl who have progressed to chronic infxn need tx (minimizes dz by preventing
replication…ANTI-virals (LAMIVUDINE) and other nucleoside RTI, interferon alfa
◦Pregnant women prior to delivery if Hep B positive give newborn baby Anti-Hep B immunoglobulin along with Hep B vaccination for both active
and passive immunity
‣ uses reverse transcriptase (like HIV), though NOT technically a retrovirus-doesnt integrate into the host chromosome
susceptible/natural/immunization/acute/chronic/? CHART
2
Q
What are the causes of SBO (small bowel obstruction) <4>
A
- bilious vomiting
- abdominal distention
- air fluid levels
- small bowel dilatation
3
Q
Vitamin Deficiencies
- Thiamine
- Retinoic acid
- Riboflavin
- Pyridoxine
- Niacin
- Abscorbic acid
- Cobalamin
A
1.Thiamine (Vitamin B1) deficiency (this one is mine)
>associated with infantile and adult beriberi and Wernicke-Korsakoff syndrome in alcoholics
>infantile beriberi: age 2-3 mo, include fulminant cardiac syndrome with cardiomegaly, tachycardia, cyanosis, dyspnea, and vomiting
>>Adult:
dry: symmetrical peripheral neuropathy accompanied by sensory and motor impairments, especially distal extremities
wet: dry neuropathy and cardiac involvement (cardiomegaly, cardiomyopathy, CHF, peripheral edema, tachycardia)
>>CP: high output congestive HF and neuro symptoms
- Retinoic acid/Vit A deficiency: (Ret is an A student)
>>CP: night blindness, xerophthalmia, and vulnerability to infection (especially measles)
3. Vit B2 (Riboflavin) deficiency: (flava, peace out)
>>CP: cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization, and ariboflavinosis
- Pyridoxine (Vit B6) deficiency: (pyramid at 6)
>>CP: cheilosis, glossitis, dermatitis, peripheral neuropathy
- Niacin (Vit B3) deficiency: (n-i-i-i-ce)
>>CP: pellagra (dementia, dermatitis, and diarrhea)
- Absorbic acid (Vit C): (A-B-C)
>>CP: scurvy (hemorrahge, bleeding into joint spaces, gingival swelling, impaired wound healing, weakened immune response to local infections)
- Cobalamin (Vit B12) deficiency:
>>frequently associated with pernicious anemia
>>CP (of pernicious anemia): older, mentally slow woman of N. European descent who is “lemon colored” (anemic and icteric), has a smooth, shiny tongue indicative of atrophic glossitis, and demonstrates a shuffling broad-based gait
4
Q
Hemochromatosis
A
- mutation: HFE prot most common
- HFE inactivation= decrease in hepcidin synthesis by hepatocytes and increase in DMT1 expression by enterocytes =iron overload
- at increased risk for liver cirrhosis and HCC (hepatocellular carcinoma)
- in women progression is slowed by physiologic iron loss through menstruation and pregnancy
- late stage: bronze diabetes
- Triad: skin hyperpigmentation, DM, pigment cirrhosis with hepatomegaly
5
Q
Carcinoid tumors
A
- confined to the intestine
- dont cause carcinoid syndrome because secretory products are metabolized by liver before entering systemic circulation
- VERSUS
- intestinal carcinoids: metabolize to the liver and extraintestinal (bronchial)
- carcinoids release vasoactive substances that AVOID first-pass metabolism
- avoidance of first pass leads to carcinoid syndrome
- composed of islands/sheets of uniform cells with eosinophilic cytoplasm and oval-to-round stippled nuclei
- derived from neuroendocrine cells inthe GI tract
- most appendiceal carcinoids are enign
- may cause appendicitis
- rarely: carcinoid syndrome with liver metastasis
- CP: flushing, diarrhea, bronchospasm
6
Q
Schilling Test
A
- help differentiate between dietary deficiencyof vit B12, pernicious anemia, and malabsorption syndromes
- low absorption of cobalamin not correctableby IF=malabsorption due to
- ileal disease
- pancreatic insufficiency
- bacterial overgrowth
7
Q
Hepatic angiosarcoma
A
- associated with exposure to carcinogens:
- arsenic
- polyvinyl chloride
- thorotrast
- tumor cells express CD31, an endothelial cell marker
8
Q
What is one of the most common causes of folate deficiency anemia?
A
- Alcoholism!
- can develop in weeks
- peripheral smear: macrocytosis, ovalocytosis, neutrophils with hypersegmented nuclei
9
Q
Colorectal adenocarcinoma
A
- prognosis directly related to STAGE of tumor (NOT to the grade!!)
- stage=extent of tumor expansion
- grade=degree of tumor differentiation
- well-differentiated–to–anaplastic
10
Q
Barrett’s esophagus
A
- metaplastic condition; nml squamous epithelium of distal esophagus is replaced by intestinal-type columnar cell
- gross enoscopy: tongues of beefy red mucosa extending above the lower esophageal sphincter into areas of nml pale pink squamous mucosa
- can occur in trachea of chronic smokers
- complication of long-standing GERD
- increased risk of esophageal adenocarcinoma
11
Q
Dubin-Johnson syndrome
A
- benign D/O
- defective excretion of bilirubin gluco across canalicular mebrane=direct HYPERbilirubinemia and jaunduce
- gross: black liver due to impaired excretion of epi metabolites
- histo: dense pigments within lysosomes
12
Q
tenia coli
A
3 seperate smooth muscle ribbons that travel longitudinally on outside of colon, converge at root of vermiform appendix (help find appendix)
13
Q
acute appendicitis
A
- cause: obstruction of lumen of the appendix
- most common obstructors: fecaliths (can also be: hyperplastic lymphoid follicles, foreign bodies, nematodes, carcinoids)
- retained mucus causes appendicular wall to distend which impairs venous outflow
- resulting hypoxia causes ischemia and associated bacterial invasion
- inflamm fluid and bacterial contents can spill into the peritoneal cavity, causing peritonitis
- CP: RLQ abdo pain, N/V/D, fever
14
Q
adenoma to carcinoma sequence
A
- nml colon-APC INactivation
- HYPERproliferative epithelium-methylation abnormalities COX2 OVER-expression
- Adenoma
- K-ras activation
- DCC INactivation
- p53 INactivation
- further accumulation of genetic abnormalities leads to CARCINOMA
15
Q
Pringle manuever
A
- occlusion of portal triad to get source of RUQ bleed
- if hepatic bleeding persists afterocclusion of the portal triad, the IVC or hepatic veins are likely to be injured
16
Q
chronic alchoholic pancreatitis
A
- hx: epigastric calcification and hx of alcohol abuse
- alcohol inducted secretion of protein rich fluid
- protein secretions precipitate within pancreatic dicts and leads to ductal plugs which calcify and obstruct
- leads to exocrine insufficiency
- impedes secretion of -ases and thus get malabsorption (diarrhea/steatorrhea)
- CP: weight loss, bulk frothy stools
17
Q
Nutrient deficiencies associated with malabsorption
A
- anemia-Fe, folate, B12
- muscle wasting and edema-protein
- petechiae and easy bruising-Vit K
- bone pain, muscle weakness, tetany-Vit D, Ca2+
- hyperkeratosis + night blindness-Vit A
18
Q
Polyethylene glycol
A
- osmotic laxative
- diarrhea associated with lactase deficiency
19
Q
Gilbert syndrome
A
- common familial disorder to bilirubin glucuronidation with reduced production of UDP glucuronyl transferases
- pts with no apparent liver dz who have mild unconjugated HYPERbilirubinemia that appears provoked by one of the classic triggers:
- hemolysis, fasting, physical exertion, febrile illness, stress, fatigue
20
Q
hepatic metab of bili
A
- uptake from bloodstream
- storage within hepatocyte
- conjugation with glucoronic acid
- biliary excretion
21
Q
Gallstone ileus
A
- mechanical bowel obstruction caused when a large gallstone erodes into the intestinal lumen through a cholecystoenteric fistula
- pneumobilia (air in the biliary tract) is common finding (abdo x-ray)
- may come to rest in the ileum, which has the smallest lumen of the intestinal tract
22
Q
pernicious anemia
A
- vitamin B12 deficiency
- caused by autoimmune destruction of parietal cells (chronic atrophic gastritis)
- parietal cells secrete HCl and IF and are found primarily in the superficial regions of the gastric glands
23
Q
Cirrhosis
A
- end stage of many chronic liver diseases
- characterized by:
- diffuse hepatic fibrosis with replacement of the nml lobular architecture by fibrous-lined regenerative parenchymal nodules
- most common causes:
- chronic viral hepatitis (Hep B and C)
- alcohol
- hemochromatosis
- non-alcoholic fatty liver dz
- in advanced cirrhosis get portal HTN from increased resistance to hepatic blood flow which can lead to developement of gastroesophageal varices
- untx varices are prone to rupture and can result in a massive GI hemorrhage and possbily death
24
Q
Leptin
A
- protein hormone produced by adipocytes in proportion to the quantity of fat stored
- tells the body: “IM FULL, STOP EATING”
- acts on the arcuate nucleus of the hypothalamus to inhibit production of <pomc> <em>neuropeptide Y</em> (decreasing appetite) and stim production of alpha-MSH (increasing satiety)</pomc>
- mutations in the leptin gene or receptor result in hyperphagia and profound obesity
- sustained elevation in leptin levels from the enlarged fat stores results in leptin desensitization
25
Intussusception
* invagination of a portion of the intestine into the lumen of the adjacent intestinal segment (*collapsed telescope*)
* CP: intermittent, severe, colicky abdo pain, "**currant jelly**" stools (contain blood and mucus), sometimes, a palpable mass in the RLQ
* typical location: ileocolic jxn
* **most common in kids\<2 yo**
* in kids \>2yo seek out a lead pt:
* Meckel diverticulum
* foreign body
* intestinal tumort
* *barium enema* is diagnostic, may be therapeutic
* if doesnt resolve things, sx intervention is mandated
26
Primary biliary (BARBARA is an ALIEN) cirrhosis
* chronic liver disease charac. by **_autoimmune_ destruction** of the intrahepatic bile ducts and **cholestasis** (jaundice, pale stool, dark urine) by *granulomatous inflamm*
* epid: **middle-aged WOMEN**, insidious onset
* first CP: **pruritis** (severe at night) + fatigue
* physical findings: **hepatosplenomegaly** and **xanthomatous** (hypercholesterolemia) lesions in the eyelids or in the skin and tendons
* as dz progresses: jaundice, steatorrhea, portal HTN, and osteopenia
* lab: elevated alk.phos + cholesterol, elevated serum IgM
* Diagnosis confirmation: demo of anti-mitochondrial Ab in serum
* associated conditions (yayyy, ai dz for dayz): Sjögren's syndrome, Raynaud's syndrome, scleroderma, a.i. thyroid dz, hypothyroidism, celiac dz
27
Most common intra-abdo infections
* usually **polymicrobial**
* ***B. fragilis & E coli***=most prominent organisms isolated
28
H pylori
* found in greatest concentration in the prepyloric area of gastric antrum
* biopsy of prepyloric area will hav egreatest yield of the organism
* noninvasively detected with urease breath test
* pt consumes 13C-labeled urea and breath monitored
* HP produces urease
* false negs from AB or PPI during the 2-4 wks prior to the test
29
gastric acid secretion
* cephalic and gastric phases stim GAS, intestinal influences reduce GAS
30
Metastasis of gastric cancer
* **Virchow's node**-mets to the **L. supraclavicular** sentinel node (first clinical manifestation of occult gastric ca)
* **(intestinal) Sister Mary Joseph**-mets to **periumbilical** region, get subq mass
* **(diffuse) Krukenburg** tumor:
* in women met spread of adenocarcinoma to one or both ovaries in association with primary ca of stomach, breast, pancreas, gallbladder
* mucin-producing, **signet-ring** neoplastic cells in the ovarian stroma
* one of the most common types of metastatic ovarian ca
31
Malabsorption
* syndrome of impaired intestinal digestion and absorption
* fats are typically most severely affected
* test for stool fat: Sudan 3 stain=most sensitive to screen for malabsorptive d/o
* CP for significant malab: diarrhea, steatorrhea (bulky, foul-smelling; visible oil droplets, greasy toilet ring)
* most often: nonspecific s/s: weight loss, fatigue, vague abdo discomfort
* general malsb is common due to defects in:
* pancreatic secreetion (chronic pancreatitis, CF)
* mucosal d/o (celiac dz, inflamm bowel dz)
* bacterial overgrowth (surgical alteration in GI tract anatomy, abnml motility)
* parasitic dz (Giardia)
32
Chronic alcoholic pancreatitis (booze and ca.butt.plugs)
* CP: epigastric calcification and hx of alcohol use
* develops in pt due to alcohol-induced secretion of **protein-rich fluid**
* proteinaceous secretions can precipitate within the pancreatic ducts forming **ductal plugs** that may **calcify** and be detectable on abdo imaging
33
CCK (EYE)
* hormone responsible for:
* **GB contraction**
* DEC gastric emptying...slowww downnn
* INC pancreatic enzyme secretion (by acinar cells)
* made by **I cells** in duodenum + jejunum in response to FA + AA when fat/protein-rich chyme enter the duodenum
* 3 well known RF for gallbladder dz: **forty, fat, female**
34
Dietary Lipids
* TG, phospholipids, cholesterol esters-primarily digested in duodenum via action of pancreatic enzymes (lipase, phospholipase A2, cholesterol esterase)
35
CREST syndrome
* **calcinosis**
* **raynaud** phenomenon
* **esophageal** dysmotility
* result of atrophy and fibrous replacement of the muscularis in the lower esophagus
* esophageal body and LES become atonic and dilated=s/s of gastroesophageal reflux (heartburn, regurgitation, dysphagia)
* increased risk of barrett's esophagus and fibrous stricture formation
* **sclerodactyly**
* **telangiectasia**
* [limited variant of systemic sclerosis with skin dz that primarily affects the *face, forearms, fingers*]
36
Statins
* first line for pts with hypercholesterolemia
* competitively inhibit HMG CoA reductase (enzyme responsible for conversion of HMG CoA to mevalonate)--rate-limiting step in hepatic cholesterol synthesisi
* inhibition decrease hepatic cholesterol synthess
* resulting upregulation of LDL receptors causes increased uptake of LDL from circulation
37
Bile acid-binding resins
* work by binding bile aceids in the GI tract and thus interfere with the enterohepatic circulation of bile acids and causing increased bile acid excretion
* result: hepatic synthesis of new bile acids-consumes liver cholesterol stores
* combo therapy with statins=increased hepatic cholesterol and bile acid synthesis
38
Hepatic Abscess
* CP: fluid-filled cavity inthe liver in conjunction with fevers, chills, and RU abdo pain
* in LSEC high incidence, usually caused by parasitic infections
* in HSEC uncommon, caused by bacterial infection (80% of cases)
* pyogenic bacteria gain access to liver through:
* biliary tract infection (ascending cholangitis)
* portal vein pyemia (bowel or peritoneal sources)
* hepatic artery (ystemic hematogenous seeding)
* direct invasion from adjacent source (peritonitis, cholecystitis)
* penetrating trauma or injury
39
Hep B infection
* one of the most common causes of hepatic injury in the US, frequently sexually transmitted or via percutaneous inoculation (IVDU)
* accumulation of hep B surface Ag within infected hepatocytes
* histo: finely granular, homogeneous, dull eosinophilic inclusions that fill the cytoplasm (ground glass hepatocytes)
* other nonspecific morphologic changes: hepatocyte necrosis (ballooning degeneration) and apoptosis, steatosis, portal inflamm with mononuclear inclusions (lymphocytes, macrophages)
40
Traveler's diarrhea
* most frequently related to enterotoxigenic E. coli (gram neg motile enteric rods) that produces heat labile and heat stable enterotoxins
* LT enterotoxin (similar to cholera toxin) activated adenylate cyclase leading to increased intracellular cAMP
* ST enterotoxin (heat stable) activates guanylate cyclase leading to increased intracellular cGMP
* both cause water and electrolyte loss and watery diarrhea
41
Crigler-Najjar syndrome
* AR d/o of bilirubin metabolism caused by genetic lack of UGT enzyme needed to catalyze bile glucuronidation
* unconjugated hyperbilirubinemia develops in these infants, causing kernicterus and often death
42
Inhaled anesthetics-Halothane
* can be associated with a highly lethal fulminant hepatitis that cannot be distinguised histoogically from acute viral hepatitis
* CP: fever, anorexia, nausea, myalgias, arthralgias, rash
* PE: tender hepatomegaly (reflecting widespread liver inflamm) and jaundice
* pts have significantly elevated aminotransferease levels due to massive hepatocellular injury and prolonged prothrombin time due to failure of hepatic synthetic function
* deficiency of factor 7 (shortest t1/2 of all the procoagulant factors)
43
Acute Hep A infection
* liver biopsy findings and recent travel to an endemic region
* histo: spotty necrosis with ballooning degeneration (hepatocyte swelling with wispy/clear cytoplasm), councilman bodies (eosinophilic apoptotic hepatocytes) and mononuclear cel infiltrates
* CP: acute: prodrome of fever, malaise, anorexia, N/V, RUQ abdo pain
* several days (approx 1 wk): less prodromal; signs of cholestasis--jaundice, pruritus, dark-colored urine (due to increased conjugated bilirubin levels) and alcoholic stool (lacks bilirubin pigment)
* prog: self-limited, does NOT progress to chronic hep, cirrhosis, or hepatocellular carcinoma
44
Trypsin and hereditary pancreatitis
* trypsin can activate all the proteolytic pancreatic enxymes, including its own zymogenic form
* premature activatio of trypsinogen before it reaches the duodenal lumen can result in auto-digestion of the pancreatic tissues
* multiple inhibitory mechanisms exist to reduce the premature activation including cleavage inactivation of trypsin by trypsin itself
* gene muts that render trypsin insensitive to cleavage INactivation cause hereitary pancreatitis
* mut involving the trypsinogen or SPINK1 gene
45
Crohn's dz
* PP:
* assoc with mut in NOD2 resulting in decreased activity of the NFKB protein with reduced cytokine production=impaired innate barrier fxn of intestinal mucosa-allows intestinal microbes to induce exaggerated response by adaptive immune system=chornic GI inflamm
* increased activity of TH1 helper cells increases production of IL-2, interferon-gamma, and TNF, causing subsequent intestinal injury
* **noncaseating granulomas** seen on light microscopy of the intestine--resemble sarcoid granulomas
* causes transmural inflammation of any area of the GI tract
* most common complication: strictures and fistula formation
* granulomas NOT seen in UC
* other classic crohns findings:
* linear or serpingenous ulcerations
* cobblestone appearance of the mucosa
* transmural inflamm infiltrate (ENTIRE thickness)
* associated with oxalate kidney stones
* impaired bile acid absorption in the terminal ileus leads to loss of bile acids in feces with subsequent fat malabsorption
* lipids then bind calcium ions, resulting soap complex is excreted
* free oxalate (nmly bound by calcium to form an unabsorbable complex) is absorbed and forms urinary calculi (enteric oxaluria)
* perianal dz (skin tags, fissures) are also common
46
ulcers and gastroduodenal artery
* gastroduodenal artery lies slong posterior wall of the duodenal bulb and is likely ot be eroded by posterior duodenal ulcers
* uleration into the gastroduodenal artery can be a source of life-threatening hemorrhage
47
extrahepatic biliary atresia
* occurs due to complete obstruction of extrahepatic bile ducts
* pts develop persistent jaundice around 3rd or 4th wk of life accompanied by: dark urine, alcoholic stools and a conjugated hyperbilrubinemia
* liver biopsy: marked intrahepatic bile ductular proliferation portal tract edema and fibrosis, and parenchymal cholestasis
48
C diff tx
* Tx:
* oral metronidazole for mild to moderate cases
* vancomycin for severe cases
* also: fidaxomicin-macrolytic AB (related to macrolides) inhibits sigma subunit of RNA polymerase=inhibition of protein synthesis and cel death
* bacterocidal, minimal systemic absorption, narrow spectrum
* in the absence of nml intestinal microbial flora (ex: after a course of AB), C diff can overgrow and produce enterotoxin (toxin A) and cytotoxin (toxin B)
* Clinical dz from c diff: transient diarrheas to severe pseudomembranous colitis
* white/ylw membrane-like plaques on colonoscopy=pathognomonic
49
chronic non-atrophic gastritis
* most often due to H pylori infection whic primarily affects the antrum and in time spreads to gastric body
* acute phase: inflamm infiltrate has neutrophils; chronic: lymphocytes, lymphoid follicles, and plasma cells
* involvement of the gastric body in longstanding infection is associated with n increased risk of gastric adenocarcinom and mucosa-associated lymphoid tissue (MALT) lymphoma
50
Cholestatic liver disease
* can cause malabsorption and nutritional deficiencies of fat-soluble vitamins
* intrahepatic auses of cholestasis:
* drug induced (erythromycin, contraceptives)
* primary biliary cholangitis
* cholestasis of pregnancy
* primary sclerosing cholangitis
* extraheptaic:
* cholendocholithiasis
* malignancy (eg pancreatic, gallbladder)
* end up with deposition of bile pigment within the hepatic parenchyma, with green-brown plugs in the dilated bile canaliculi
* when prolonged, reduction in bile flow causes intestinal malabsorption of fats and fat-soluble vitamins (ADEK) which require bile salts for digestion
51
Celiac dz
* IgA anti-tissue transglutaminase and IgA endomysial Ab are very sn and sp for diag of celiac
* small intestinal biopsy is confirmatory
* strophy of villi, flattening of mucosa, chronic inflam of lamina propria
* histo: severe atrophy and blunting of the villi along with a chronic inflammatory infiltrate of the lamina propria
* CP: diarrhea, steatorrhea, nutritional deficiencies
* tx: gluten-free diet
52
Niacin
* decreases hepatic synthesis of triglycerides and VLDL and reduces clearance of HDL
* Niacin can decrease renal excretion of uric acid, precipitating acute gouty arthritis
53
colonic diverticular
* often involve the sigmoid and develop due to increased intraluminal pressure (PULSION) created during strained bowel movements (due to chronic constipation) causing outpouching of the mucosa and submucosa through the muscularis (false diverticula)
* cp: \>60yo, may be asymptomatic or present with hematochezia or diverticulitis
54
Diphenoxylate
* opioid anti-diarrheal drug
* binds mu opiate receptors in the gut to **slow motility**
* overuse can lead to euphoria and physical dependence
* to discourage abuse, is combined with **atropine** which induces adverse effects if taken in high doses
55
Stress-related mucosal dz
* usually caused by local ischemia in the setting of severe physiologic stress (shock, extensive burns, sepsis, severe trauma)
* ulcers arising in the setting of severe trauma/burns =Curling's ulcers (curling iron)
* ulcers from intracranial ulcers caused by direct vagal stimulation=Cushing's ulcers (brain cushioning)
56
Zenker "false" diverticulum
* CP: elderly pts with oropharyngeal dysphagia, halitosis, regurgitation, and recurrent aspiration
* PP:
* diminished relaxation of cicopharyngeal muscles during swallowing results in increased intraluminal pressure in the oropharynx
* may eventually cause the mucosa to herniate through a zone of muscle weakness in the posterior hypopharynx forming a Z-d
57
SMA syndrome
* when the transverse portion of the duodenum is entrapped between the SMA and aorta
* CP: s/s of partial intestina obstruction
* PP: when the aortomesenteric angle critically decreases, secondary to diminished mesenteric fat, pronounced lordosis, or surgical correction of scoliosis (lengthens the spine)
* also occurs with low body weight, recent weight loss, severe burns or other inducers of catabolism, and prolonged be drest
58
External hemorrhoids
* originate below the dentate line
* covered by modified squamous epithelium and have cutaneous (somatic) nervous innervation from the inferior rectal nerve (branch of the pudendal nerve)
* branches of pudendal supply the perineum and external genitalia in males and females and are very sensitive to touch, temperature, and pain
* CP: generally asymptomatic, can become painful if they thrombose
59
Internal hemorrhoids
* originate above the dentate line
* covered by columnar epithelium
* autonomic innervation from th einferior hypogastric plexus-which is only sensitive to stretch and not pain, temp, or touch
60
D-xylose
* monosaccharide whose absorption is not affected by exocrine pancreatic insufficiency, can be used to differentiate between pancreatic vs. mucosal causes of malabsorption
61
organisms that can cause diarrhea with only a small inoculum
* Campylobacter jejuni (500 cells)
* E. histolytica (1-10 organisms)
* G. lamblia (1-10 organisms)
* Shigella (10-500 cells)
62
Shigellosis
* infectious dz that can be causes by variety of Shigella species
* in industrialized, S. sonnei is most commont causes
* shigella incades the GI mucosa by gaining access to microfold cells in ileal Peyer pathches through endocytosis
* Shig then lyses the endosome and spreads laterally into other epithelial cells, causing cell death and ulceration with hemorrhage and diarrhea
63
CV dysphagia
* can result from pressure on the esophagus by a dilated LA
* LA commonly enlarged in pts with mitral stenosis and LV failure
64
Diffuse esophageal spasm
* CP: periodic, simultaneous and non-peristaltic contractions of the esophagus due to impaired inhibitory innervation within the esophageal myenteric plexus
* Cp: liquid/solid dysphagia and CP due to inefficient propulsion of food into the stomach, heartburn, and food regurg
65
Gastric varices
* dilated submucosal veins that can cause life-threatening bleeding in the upper GI tract
* PP: portal HTN (which can be a complication of cirrhosis)
* also seen with: splenic vein thrombosis due to: chronic pancreatitis, pancreatic ca, and abdominal tumors
* splenic vein runs along the posterior surface of the pancreas and can develop a blood clot from pancreatic inflammation
* short gastric veins drain the fundus of the stomach into the splenic vein
* splenic vein thrombosis can increase pressure in the short gastric vein and cause gastric varices only in the fundus
* rest of the stomach and esophagus are usually unaffected
66
Acute interstitial pancreatitis
* pancreas is grossly edematous
* light microscopy: focal areas of fat necrosis, calciu deposition, interstitial edema
* in necrotizing (hemorrhagic) pancreatitis, chalky-white areas of fat necrosis interspersed with hemorrhage are seen on macroscopic examination
67
gallstone formation
* elevated cholesterol concentrations increase the likelihood of cholesterol precipitation and gallstone formation
* decreased cholecystokinin release due to lack of enteral stimulation (in pts receiving total parenteral utrition) contribs to development of gallstones
* resection of ileum can also contrib, due to disruption of nml enterohepatic circulation of bile acids
* high levels of bile salts and phosphatidylcholine increase cholesterol solubility and decrease the risk of gallstones
68
Primary lactase deficiency
* congenital or acquired
* congenital: rare AR
* acquired: more common, typically arises from decreased or ceased production of lactase by mid childhood (lactase nonpersistence) or inflamm d/o affecting the intestinal brush border
* common in pts of Asian or African acnestry (and hispanic and Native Americans)
* small bowel mucosa is nml on histo
* pp: undigested lactose causes osmotic diarrhea and acidification of the stool
69
Esophageal SCC
* histopath: solid nests of neoplastic squamous cells with abundant eosinophilic cytoplasm and distinct borders
* also: aread of keratinization and presence of intercellular bridges
* CP: progressive solid and eventually liquid dysphagia and weight loss; retrosternal discomfort/burning and significant weight loss
70
Hep C
* CP: fever, jaundice, anorexia in an IVDU
* acute viral hepatitis causes hepatocyte apoptosis and necrosis
* apoptotic hepatocytes shrink, undergo nuclear fragmentation and become intensely eosinophilic
* may be referred to as acidophilic bodies, councilman bodies, and apoptotic bodies
71
Abetalipoproteinemia
* inherited inability to synthesize apolipoprotein B (important component of chylomicrons and VLDL)
* lipids absorbed by the small intestine cannot be transported into the blood and accumulate in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm
* AR loss of function mutation in the MTP gene
* CP: in first yr of life-s/s/ malabsorption (abdo distention, foul-smelling stool)
* lab studies: very low TG and cholesterol; chylomicrons, VLDL, apoB absent
* causes RBC with abnml membranes and thorny projections=acanthocytes and multiple neuro abnormalities
72
Right-sided Colon CA
* usually grow as exophytic masses
* grow as large bulky masses that protrude into colonic lumen due to the relatively large caliber of ascending colon
* CP: occult bleeding and symptoms of iron deficiency anemia (fatigue, pallor)
* non-specific s/s: anorexia, malaise, unintentional weight loss
* PP: infiltrate intestinal wall, encircle lumen, cause constipation and symptoms of intestinal obstruction
* rectosigmoid involvement often causes hematochezia
* \*\*ascending colon
* livers and lung=common site of metast
* [left sided tumors (rectosigmoid colon) tend to be smaller]
73
Pancreatic ca RF
* age-highest 65-75yo
* smoking=most important environmental RF, DOUBLES the risk
* DM: higher pan ca risk with duration of DM
* chronic pancreatitis-risk is highest after 20yr of chronic pan
* genetic predisposition: hereditary pancreatitis, MEN syndromes, hereditary nonpolyposis colon ca, familial adenomatous polyposis sundromes
* adenocarcinoma at the head of the pan compression common bile duct
* CP: palpable, but nontender GB (Courvoisier sign), weight loss, obstructive jaundice (assoc with pruritus, sark urine, pale stools)
* ca of body and tail dont obstruct CBD, no s/s till they invade the splanchnic plexus and cause midepigastric abdo pain
74
Anal fissures
* longitudinal tears in the mucosa
* usually due to the passage of hard stool in pts with chronic constiation
* most occur at the posterior idline, likely due to decreased blood flow in this area
75
GB hypomotility
* GB fxn: actively absorb water from bile
* GB hypOmotility (biliary stasis) causes bile concentration which promotes bile precipitation and accumulation of viscous biliary sludge that predisposed to gallstone formation (espec cholesterol stones) and bile duct obstruction
76
Primary biliary cholangitis
* chronic autoimmune liver dz
* Charac: lymphocytic infiltrates and destruction of small and mid-sized intrahepatic bile ducts
* similar findings in GvHdz
* donor T cells migrate to host tissue, recog host MHC Ag as foreign
* slin, liver, GI tract-most commonly affected areas
77
VIPomas
* pancreatic islet cell tumors
* hypersecrete vascoactive intestinal peptide (VIP) which increases intestinal chloride loss into the stool and causes excess losses of the accompanying water, sodium, potassium (secretory watery diarrhea, often \>3L/day)
* CP: watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome (pancreatic cholera)
* VIP also inhibits gastric acid secretion
* Somatostatin inhibits the secretion of VIP and is used to tx the symptoms of VIPoma
78
Secretin
* hormone produced by duodenal S-cells and releasedin response to increased duodenal H+ concentrations
* stimulates pancreatic ductal cells to increase bicarb secretion in order to neutralized the acidity of the gastric contents entering the duodenum
79
Gastrojejunostomies and Iron
* *DJ pumps IRON in the gym*
* iron absorption occurs predominantly in the duodenum and proximal jejunum
* bypass of this segment of small bowel by gastrojejunostomy results in iron deficiency anemia
* malabsorption of vit b12, folate, ADEK (especially Vit D), and Calcium may also be observed followin gastric bypass procedures
80
Gastroesophageal reflux dz (GERD)
* cause: gastroesophageal jxn incompetence and can be associated with extraesophageal symptoms (eg nocturnal cough) in the absence of heart burn
* acidic gastric contents irritate the esophageal mucosa leading to characteristic histologic findings that include:
* basal zone hyperplasia
* elongation of the lamina propria papillae
* scattered eosinophils and neutrophils
81
UC
* long standing UC is associated with an increased risk of colorectal ca
* duration and extent of colitis are the most significant RF
* unlike sporadic colorectal ca, colitis-associated carcinomas are more likely to arise from non-polypoid dysplastic lesions, be multifocal in nature, develop early p53 muts and late APC gene muts, and be of higher histological grade
82
How should you follow-up a moderately elevated alk phos of unclear etiology?
* gamma-glutamyl transpeptidase
* -enzyme predominantly present in hepatocytes and biliary epithelia
* -GGTP is not significantly present in the bone
83
Vit E deficiency
* can occur in indivs with fat malabsorption
* deficiency is associated with increased susceptibility of the nuronal and erythrocyte membranes to oxidative stress
* CP: ataxia, impaired proprioception, vibratory sensation, hemolytic anemia and neuromuscular dz (skeletal myopathy, spinocerebellar ataxia, polyneuropathy)
84
lactase deficiency
* can be due to:
* an inherited AR d/o
* progressive non-persistence of lactase expression in adulthood
* inflamm d/o affectng the intestinal brush border
* undigested lactose causes osmotic diarrhea and acidification of the stool
85
Hep B and Hep D ship
* Hep B surface Ag of hep B virus must coat the hep D antigen of hep D virus before it can infect hepatocytes and multiple
* HDAg is replication defective
* HDV infection can arise either as an acute coinfection with HBV or as a superinfection of a chronic HBV
86
Watershed areas
* primarily:
* left colon at the splenic flexure (border between SMA and IMA supply)
* rectrosigmoid jxn (border betwen sigmoid artery and superior rectal artery)
* susceptible to ischemic damage during hypotensive states (espec in pts with underlying arterial insufficiency)
* impaired infusion to bowel leads to ischemia and necrosis of intestinal wall
* complications: acidosis, sepsis, gangrene, perforation
* colonoscopy: pale mucosa and petechial hemorrhages
87
Acute acalculous cholecystitis
* acute inflamm of the GB in the absence of gallstones
* typically occurs in critically ill pts (those with sepsis, severe burns, trauma, immunosuppression) due to GB stasis and ischemia
* CP: subtle, include: fever, RUQ pain, leukocytosis, mid elevations in LFTs
* PE: jaundice, palpable RUQ mass
* diagnostic: ultrasound
88
GI ulcers
* peptic ulcers-chronic lesions in areas exposed to acid/peptic juices, most common:
* proximl duodenum, antral stomach, GEJ
* CP: epigastric discomfort, early satiety, positive fecal occult blood test
* almost all due to either HP infection or use of NSAIDS
* duodenal ulers-rarely malignant, dont need biopsy
* not associated with increased risk of carcinoma in the same location
* gastric ulcers-can be malignant, need biopsy
* ones caused by HP are associated with increased risk of gastric ca
89
Reye syndrome
* in kids with febrile illness treated with salicylates (aspirin)
* CP: hepatic failure and encephalopathy
* Hep dysfxn: vomiting and hepatomegaly; increased ALT, AST, ammonia, biliruin, prolonged PT and PTT
* light microscopy: miscrovesicular steatosis sans inflamm and cerebral edema
* enceph: due to hepatic dysfxn and toxic effect of hyperammonemia
* !!to avoud inducing RS, aspiring should NOT be admin to children \<16yo except for very specific circumstances: Kawasaki dz
90
POLYPS
* neoplastic:
* serrated
* adenomatous (tubular, vilous, tubulovillous)
* villain, can undego malignant transformation
* villous (sessile, larger) more likely than tubular
* villous adenomas can cause bleeding, secretory diarrhea, partial intestinal obstruction
* NON-neoplastic-usually dont progress in to adenocarcinoma of the colon
* nyperplastic
* submucosal
* inflammatory
* mucosal
91
Zollinger-Ellison syndrome
* PP: gastrin hypersecretion (gastrin-secreting tumors-gastrinomas) induces parietal cell hyperplasia causing visibile enlargment of gastric folds on endoscopy
* involves the small int or pancreas
* increased gastric acid secretion induced by excess gastrin also causes:
* peptic ulcer dz, heartburn, abdo pain/acid reflux, diarrhea
* frequently assoc with multiple endocrine neoplasia type 1
* respond poorly to therapy
* multiple peptic ulcers that may involve the distal duodenum
92
Fibrates
* inhibit cholesterol 7-alpha hydroxylase (which catalyzed the rate-limiting step in the synthesis of bile acids)
* reduced bile acid production results in decreased cholesterol solubility in bile and favors the formation of cholesterol gallstones
93
Acute cholecystitis
* CP:
* recurring abdo pain
* positive ultrasoic Murphy sign
* multiple cholesterol gallstones
* PP: gallstones obstructing the cystic duct
* diag: identifying signs of GB inflamm (wall thickening, pericholecystic fluid) on ultrasonography
* when US is inconclusvie, nuclear med hepatobiliary screening (cholescintigraphy) can be used to assess cystic duct patency and make diag
94
Gastric adenocarcinoma
* 2 morphilogical variants
* **intestinal type**-forms a (well demarcated) bulky/solid mass that projects into the stomach lumen and is composed of glandular-forming cuboidal or columnar cells
* **diffuse** carcinoma (linitis plastica)-infiltrates stomach wall and displays signet-ring cells (cells with abundant mucin droplets that push nucleus to one side) on light microscopy; gross stomach wall thickening
95
Familial hypercholesterolemia
* one of the most common AD d/o
* result of heterozygous or homozygous LDL receptor gene muts which cause hepatocyte under-expression of fxnl LDL receptors
* can lead to accelerated atherosclerosis and early-onset coronary artery dz
96
Hirschsprung dz
* submucosal (meissner) and myenteric (auerbach) autonomic plexi are absent in the affected segment of the bowel (neural crest cells dont migrate to the intestinal wall)
* submucosa of the narrowed area is the most superficial layer where the absence of ganglion cells can be seen
* diag: need rectal biopsy
* neural crest cells **migrate caudally**, so **rectum is always affected**
97
Alcohol-induced hepatic steatosis
* related to decrease in free fatty acid oxidation secondary to excess NADH production by the 2 major alcohol metabolism enzymes: alcohol dehydrogenase and aldehyde dehydrogenase
98
Trypanosoma cruzi
* endemic in rural areas of central and south america
* causes Chagas dz
* parasite can destroy the myenteric plexus in the esophagus, intestines, and ureters, causing secondar achalasia, megacolon, and magaureter (respectively)
99
Necrotizing enterocolitis
* one of the most common GI emergencies affecting newborns
* PP: bacterial invasion and ischemic necrosis of the bowel wall
* assoc with: prematurity and initiation of enteral feeding
* diag-abdo x-ray: pneumatosis intestinalis (air in bowel wall)
* prog: 30% of affected neonates die, espec when dz complicated by intestinal perforation
100
Porcelain GB
* potential manifestation of chronic cholecystitis
* often found in association with multiple gallstones
* PP: dystrophic intramural deposition of calcium salts in the setting of chronic inflamm
* assoc with increased risk of adenocarcinoma of the GB
101
CMV esophagitis
* can occur in transplant pts and usually presents with odynophagia or dysphagia that can be accompanied by fever or burning CP
* endoscopy: linear and shallow ulcerations in the lower esophagus
* histo: enlarged cells with intranuclear inclusion bodies
102
Acute pancreatitis
* number one cause: gallstones, folowed by alcohol abuse (2nd)--80%
* 20%: less common causes:
* ERCP prodcedure
* drugs (azathioprine, sulfasalazine, furosemide, VPA)
* infections (mumps, coxsackie, M. pneumo)
* HYPERtriglyceridemia (inherited or acquired, TG\>1000mg/dL)
* structural abnml of pancreatic duct
* sx
* HYPERcalcemia
* macrocytosis and AST:ALT ratio\>2 are indirect indicators of chronic alcohol consumption
* alcohol related macrocytosis can occur independently of folate deficiency
* common complication: pancreatic pseudocyst
* collection of fluid ich enzymes and inflamm debris
* walls consist o granulation tissue and fibrosis
* NOT lined by epithelium
103
Tropheryma whippelii
* gram positive actinomycete with glycoprotein in the cell walls
* glycoprotein colors magenta with PAS and is diastase-resistant
* Whipple dz=rare systemic illness that involves small intestine, jts, CNS
* Histo: small intestine mucosa containing enlarged, foamy macrophages packed with rod-shaped bacilli and PAS-positive, diastase-resistant granules
104
Infant and Adult botulism
* infant: frequently due to honey consumption
* \>12% honey samples have low numbers o C. botulinum spores
* s/s: constipation, mild weakness, lethargy, poor feeding
* baby may look "floppy"
* adult: form consuming preformed toxin, typically canned food
105
Important fxns of the stomach
* protein digestions
* gastric parietal produce HCl and chief cells produce pepsinogen
* HCl denatures dietary protein and converts pepsinogen to active form, pepsin
* pepsin cleaves polypeptides at aromatic AA locations
* IF secretion-parietal cells in the body and fundus of stomach secrete IF
* IF=glycoprotein the nmly binds to vit B12
* B12-IF absorbed by enterocytes in terminal ileum
* in pt with total gastrectomy, no IF is produced, vit B12 cant be absorbed
* thus, need v. high dose oral or parenteral vitB12
* Gastric reservoir
* reservoir for ingested food
* after total gastrectomy, accelerated emptying of HYPERosmolar food boluses into small bowel results in dumping syndrome (colicky abdo pain, nausea, diarrhea)
106
Portal vein thrombosis
* causes portal HTN, splenomegaly, and varicosities at portocaval anastomoses
* does not cause histo changes to the hepatic parenchyma
* ascites is uncommon as the obstruction is perisinusoidal
107
Giardia lamblia
* iodine-stained stool smear-search for O&P
* ellipsoidal cysts with smooth, well-defined walls
* most common enteric parasite in US and Canada
* common cause of diarrhea in campers/hikers
* tx: Metronidazole
108
Kaposi's sarcoma
* usually involves the skin and GI tract
* common in HIV pts not on ARV tx
* endoscopy: characteristic lesions
* range from reddish/violet flat maculopapular lesions to raised hemorrhagic nodules or polypoid masses
* Biopsy: spindle cells, neovascularization, extravasated RBC
109
Congenital pyloric stenosis
* relatively common d/o in male infants
* Charac: multifactorial pattern of inheritance
* CP: infants with recurrent projectile nonbilious vomiting
* PE: visible peristalsis and olive-sized mass in distal stomach or pyloric region
* develops secondary to hypertrophy of pyloric muscularis mucosae
* narrowing of pyloric channel is exacerbated by localized edema and inflamm
* stenosis relieved by surgical splitting of the muscle
110
Toxic megacolon
* complication of UC
* CP: abdominal pain/distention, bloody diarhhea, fever, signs of shock
* plain abdo xray=preferred diagnostic imaging study
* will show colonic dilation with multiple air-fluid levels
* Barium contrast studies and colonoscopy and contraindicted due to risk of perforation
111
What is the most common malignant hepatic lesion?
* metastasis from another primary site (eg breast, lung, colon) NOT hepatocellular carcinoma
* liver is second most common site of metastatic spread (large size, dual blood supply, high perfusion rate, filtration function of Kupffer cells)
112
Unique Characteristics of UC
1. rectum always involved
2. inflamm in mucosa and SUBmucosa only
3. mucosal damage is continuous (no areas of nml between the affected)
4. bloody diarrhea (with or without abdo pain)
113
Unique characteristics of Crohns
* transmural inflammation
* perianal fistula
* non-caseating granulomas
114
Hepatic encephalopathy
* neurologic complication of cirrhosis due in pt to liver's inability to convert ammonia (a neurotoxin) to urea
* excess ammonia is shunted past the liver and crosses the BBB leading to altered mental dtatus
* asterixis, rhythmic flapping of dorsifleed hands=common manifestation of HE
* GI bleeding can precipitate HE as hemoglobin breakdown leads to increased nitrogen products in the gut
* excess dietary protein intake (large steak meal)=another common trigger
* others: infection, sedatives, metabolic derangements (hypokalemia)
* Tx: lactulose (increase conversion of ammonia to ammonium) and Rifaximin (decreases intraluminal ammonia production)
115
acute calculous cholecystitis
* acute inflamm of GB initiated by gallstone obstruction of the cystic duct
* CP: persistent RUQ pain, fever, leukocytosis
* exam: murphy sign (inspiratory pause elicited by pain during deep palpation of RUQ)
* subsequent steps in path: mucosal disruption by lysolecithins, bile salt irritation of the luminal epithelium, PG release with transmural inflamm, GB hypomotility, increased intraluminal pressure causing ischemia, and bacterial invasion
116
Carcinoembryonic antigen (CEA)
* increased levels in colon ca and other malignancies and certain benign dz
* CEA cannot be used to diag colon ca, BUT is helpful for detecting residual dz and recurrence
117
Cavernous hemangioma
* most common benign liver tumor
* in adults 30-50yo
* congenital malformations that enlarge by ectasia
* micro: cavernous, blood-filled vascular spaces of variable size lined by a single epithelial layer
* biopsy: NOT advisable, procedure has been known to cause fatal hemorrhage and is low diagnostic yield
* prog: surgical resection for symptomatic pts or those with compression of adjacent structures
118
Major RF for esophageal ca
* SCC
* alcohol use
* tobacco smoking
* consumption of N-nitroso-containing foods
* Adenocarcinoma
* Barrett's esophagus
* GERD
* obesity
* tobacco use
119
SCC
* histo: flattened polyhedral or ovoid epithelial cells with eosinophilic cytoplasm, keratin nests "pearls" within or between cells, intercellular bridging
* also: large hyperchromatic cells with bizarre nuclei and atypical mitoses
* Qui? Middle aged/older african and asian heritage
* in asia: chewing of betel nuts
* CP: progressive solid food dysphagia and eventually liquid dysphagia that may be accompanied by weight loss
* also: chronic GI blood loss, may result in iron deficiency anemia
120
Wilson's disease
* AR d/o; charac: toxic accumulation of copper within organ tissues (especially liver, brain, eye)
* absorbed copper is used to form ceruloplasmin, which accounts for 90-95% of circulating copper
* senescent ceruloplasmin and unabsorbed copper are secreted into bile and excreted in stool=primary route of copper elimination
121
Opioid analgesics
* can cause contraction of smooth muscles int he sphincter of Oddi
* leads to increased pressure in the common bile duct and the GB
122
Chronic mesenteric ischemia
* charac: atherosclerosis of the mesenteric arteries, resulting in diminshed blood flow to the intestine after meals
* causes postprandial epigastric pain ("intestinal angina") with associated food aversion.weight loss
* path: similar to angina pectoris
* diag: duplex US or angiogaphy showing high-grade stenosis in the celiac and mesenteric arteries
123
omphalomesenteric (vitelline) duct
* connects the midgut lumen with the yolk sac cavity early in embryonic life
* nmly obliterates during 7th wk of embryonic development
* if obliteration incomplete.abnml, following abnormalities:
* persistent vitelline duct (vitelline fistula)
* meconium discharge
* Meckel diverticulum
* most common
* rule of 2's: 2% of pop, 2 ft from ileocecal valve, 2 inches in length, 2% symptomatic, males 2x more likely to be affected
* lower GI bleed=common CP
* often contains ectopic gastric mucosa which prouces acid causing possible ulceration and bleeding
* 99mmTc-pertechnetate scan identifies gastric epithelium and helps diag Meckdiv
* vitelline sinus
* vitelline duct cyst (enterocyst)
124
pigment gallstones
* composed of calcium salts of unconjugated bilirubin
* typically arise secondary to bacterial or helminthic infection of the biliary tract
* beta-glucuronidase released by injured hepatocytes and bacteria hydrolyzes bilirubin glucuronides to unconjugated bilirubin
* liver fluke: *Clonorchis sinensis* has a high prevalence in **east Asian** countries and is a *common cause of pigment stones*
125
Secretory form of IgA
* consists of 2 Ig monomers: J-chain and secretory component
* this Ig is abundant in tears, saliva, mucosa, and colostrum
* particularly important as a component of colostrum, first breast milk fed to an infant after birth, where it functions to provide the infant with passive mucosal immunity
126
Campylobacter jejuni
* campy infection is a common causes of inflamm gastroenteritis
* can be acquired rom domestic animals (cattle, sheep, dogs, chickens)
* common in farm and lab workers
* can be acquired from contaminated food, eg undercooked poultry and unpasteurized milk
* diarrhea is inflammatory (initially watery, later bloody) and accompanied by fever, abdo pain (may mimic appendicitis), and tenesmus
* infection is assoc with Guillain-Barré syndrome
127
hindgut
* encompasses distal 1/3 of the transverse colon, descending colon, sigmoid colon, and rectum
* structures receive their main arterial blood supply from the inferior mesenteric artery
128
Systemic mastocytosis
* Charac: abnml proliferation of clonal mast cells and increased histamine release
* occurs in BM, skin, and other organs
* mast cell prolif is assoc with mut in KIT receptor tyrosine kinase
* histamine causes hypersecretion of gastric acid by parietal cells in the stomach as well as a variety of other s/s (hypotension, syncope, flushing, urticaria, pruritus)
129
Mallory-Weiss syndrome
* longitudinal mucosal tears at the esophagogastric-squamocolumnar jxn
* secondary to rapid increase of intraabdo and intraluminal gastric pressure (during vomiting)
* other causes: coughing, hiccupping, abdo straining, abdo trauma
* hiatal hernias in 50% of pts with M-W, also are strong predisposing factor
* commonly associated with alcoholism
* account for 10% of cases of upper GI hemorrhage
130
secondary lactase deficiency
* can occur after viral gastroenteritis or other diseases that damage the intestinal epithelium (microvilli)
* inflamm: celiac dz
* infectious: giardiasis
* CP (after lactose ingestion):
* abdo distention
* cramping
* flatulence
* diarrhea
131
Personality D/O
132
Key Defense Mechanisms
133
Gastric bypass sx
* can cause small int bacterial overgrowth (SIBO) due to xs bacerial proliferation in blind-ended gastroduodenal segment
* SIBO results in deficiency of most vitamins (B12, A, D, E) and iron BUT, increased production of folic acid and vit K
134
chronic gastritis (with antral sparing)
* characteristic of autoimmune gastritis
* CD4+ T-cell mediated parietal cell destruction causes impaired gastric acid (...achlorhydria) and IF secretion (...pernicious anemia)
135
granulomatous gastritis
* often idiopathic BUT can be assoc w/:
* Crohn dz
* sarcoidosis
* mycobacterial infection
* characterized by: intramucosal epitheliod granulomas that cause narrowing of the antrum secondary to transmural inflammation
136
RF for gastric adenocarcinoma
* chronic gastritis
* cigarette smoking
* H pylori infection
* diet high in salt/nitrosamines -or- lacking fruits/veggies
137
Biliary Tract markers
alk phos (ALP) and GGTP
138
Liver (*cirrhosis* prognosis) markers--\<*SECRETED* by..3+1 associates\>
* PTT
* bilirubin
* cholesterol
* albumin
139
Hepatic injury markers
AST (toast to booze) and ALT (salty about hep)
140
structural integrity and cellular intactness markers
transaminases
141
How are dietary lipids digested
* 1. bile is released into the **duodenum** where bile salts **emulsify** and form **water-soluble micelles**
* 2. **jejunum**: micelles come into close contact w/ gut epithelium--facilitates passive absorption of FA, MG, and cholesterol across the brush border into the **enterocyte**
* 3. TG, phos, chol esters are reconstructed + combined w/ apoproteins --\>form chylomicrons which are released into **intestinal lymphatics**
* [most cholecystectomy pts can tolerate fatty foods because *bile is constantly being released into duodenum*]
142
CREST Path
* chronic **a.i. inflamm**
* *vascular endothelial injury* resulting in:
* chronic ischemic tissue damage
* excessive activation of **fibroblasts**--\>leading to progressive **tissue fibrosis**
143
what are the branches of the celiac trunk?
* common hepatic
* splenic
* left gastric
*
144
what are the three types of intestinal atresias
* duodenal
* jejunum/ileum
* colonic
145
duodenal atresia
* pathophys
* failure of recanalization at 8-10wks gestation
* clinical findings
* bilious or NON-bilious emesis
* **DOUBLE BUBBLE** sign on x-ray
* associations
* **DOWN SYNDROME**
146
jejunum.ileum atresia
* pathophys
* vascular injury/occlusions=ischemia of a segment of bowel--\>narrowing/stenosis or obliteration/atresia
* distal segment of ileum: spiral configuration around an ileocolic vessel=apple-peel/Christmass tree deformity
* clinical findings
* BILIOUS emesis
* abdominal distension
* associations
* gastroschisis
147
colonic atresia
* pathophys
* unknown
* clinical findings
* constipation
* abdominal distension
* associations
* Hirschsprung disease
148
hepatic steatosis
* characterized by the accumulation of large and small vesicles of fat within hepatocytes
* mc cause: excessive alcohol ingestion (alcoholic steatohepatitis)
* can also be caused by obesity (NON-alcoholic steatohepatitis/NASH)
149
chronic Hep B infection
* Hep B infection causes the hepatocellular cytoplasm to fill with hep B surface antigen
* inclusions are highly specific for hepB infection and have the following features:
* finely granular
* dull eosinophilic
* "ground glass" appearance
* (vs. hep C with lymphoid aggregtes within the portal tracts and focal areas of macrovesicular steatosis)
150
arsenic poisoning: mechanism and sources
* Mechanisms:
* bind to sulfhydryl groups
* disrupts **cellular respiration** and gluconeogenesis
* sources:
* pesticides/insecticides
* contaminated water (often from wells)
* pressure-treated wood
151
arsenic poisoning manifestattions: acute and chronic
* acute:
* GARLIC breath
* vomiting
* watery diarrhea
* QTc prolongation...torsades de pointes
* Chronic:
* hypo/HYPER-pigmentation
* HYPER-keratosis
* stocking-glove neuropathy
152
arsenic poisoning: tx
* DIMERCAPROL (British anti-Lewisite)
* increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates
* v. nary therapeutic window
* serious SE: nephrotoxicity, HTN, fever
* DMSA
153
tx for lead poisoning
* CaNa2-EDTA
* forms non-ionizing salts to INC urinary lead excretion
154
tx for iron overdoses or overload d/t multiple blood transfusions
* DEFEROXAMINE
* inds circulating iron and facilitates its urinary excretion
155
tx for methemoglobinemia
* CP of methemoglobinemia:
* gray- or blue-colored skin
* SOB
* chocolate-colored blood
* METHYLENE BLUE=tx
* artificial electron transporter for reduction of methemoglobin through the NADPH pathway
156
Galactosemia and Cataract
* lenticular accumulation of galactitol in lenses of pts with galactosemia can cause osmotic damage and development of cataracts
* cataracts may be the only manifestation of galactokinase deficiency
157
aldolase B deficiency
* hereditary fructose intolerance
* cannot metab fructose
* CP:
* hypoglycemia
* hypophosphatemia
* FTT
* reducing substances can be positive in urine
158
alpha-galactosidase A deficiency (X-linked recessive)
* Fabry dz
* CP:
* cataracts
* neuro findings:
* numbness
* tingling
* burning pain in hands and feet
* angiokeratomas
159
glucose-6-phosphatase deficiency
* converts glucose-6-phosphate to glucose
* GSD1 (von Gierke dz)
* CP:
* hypoglycemia
* LA
* hepatomegaly
* hyper-TG
160
hexosaminidase A deficiency
Tay-Sachs
CP: affected infants have retinal cherry-red spots and loss of motor skills
161
Sphingomyelinase deficiency
* Niemann-Pick dz
* CP:
* hepatosplenomegaly
* motor neuropathy
* anemia
* macular cherry-red spots
162
which non-glucose monosaccharide's metabolites can bypass phosphofructokinase
* FRUCTOSE
* result being: it is metabolized by the liver faster than the eother monosaccharides *and* is rapidly cleared form the bloodstream following dietary absorption
163
retroperitoneal organs
* SADPUCKER
* suprarenal (adrenal) glands
* aorta and IVC
* duodenum (except 1st pt)
* pancreas (head and body)
* ureters and bladder
* colon (ascending and descending)
* Kidneys
* Esophagus
* Rectum (mid-distal)
164
SADPUCKER and abdo/pelvic trauma
* retroperitoneal hematoma=common complication of abdominal and pelvic trauma
165
uncomplicated umbilical hernia
* path:
* defect at linea alba covered by skin=incomplete closure of the umbilical ring
* clinical features:
* reducible bulge at umbilicus
* notably w. INC abdo pressure (crying, pooping)
* most of them: reducible, asymptomatic, resolve spontaneously
* Associated conditions:
* Down syndrome
* hypo-thyroidism
* Beckwith-Wiedemann syndrome
166
IgA and Giardiasis
* G. lamblia causes injury to duodenal and jejunal mucosa by adhering to the intestinal brush border and releasing molecules that induce a mucosal inflamm response
* secretory IgA (which impairs adherence) is the major component of adaptive immunity vs. G. Lamblia infection
* conditions causing IgA deficiency predispose pts to chronic giardiasis
167
Hydrophilic bile acids (ursodeoxycholic acid)
* DEC biliary cholesterol secretion and INC biliary bile acid concentration=improve cholesterol solubility
* promotes gallstone dissolution
* high rate of gallstone recurrence
168
vaccines and mucosal immunity
* live attenuated oral (Sabin) poliovirus vaccine produces a stronger mucosal secretory IgA immune response than inactivated poliovirus (Salk) vaccine
* increase in mucosal IgA offers immune protection at the site of viral entry by inhibiting attachment to intestinal epithelial cells
169
riboflavin
* precursor of the coenzymes FMN and FAD
* FAD participates in the tricarboxylic acid cycle and ETC by acting as an electron acceptor for succinate dehydrogenase (complex 2)
* sucDH converts succinate into fumarate
* s/s of riblofavin deficiency:
* angular stomatitis
* cheilitis
* glossitis
* seborrheic dermatitis
* eye changes (keratitis, corneal neovascularization)
170
Hep C tx
* interferon alpha and ribavirin
* Ribavirin MOA:
* lethal HYPERmutation
* inhibits RNA polymerase and inosine monophosphate dehydrogenase (depleting GTP)=defective 5'-cap formation on viral mRNA transcripts=modulate a more effective immune response
171
RIBAVIRIN
* nucleoside antimetabolite dx, intereferes with duplication of viral genetic material
* MOA is multifactorial:
* phosphorylated intracellularly, is incorporated into RNA, causes hypermutation during RNA-dependent RNA replication=lethal to RNA viruses
* direct inhibition of HCV RNA polymerase by ribavirin triphosphate
* rib mono-P inhibits iosine monophosphate dehydrogenase=depletes intracellular pools of GTP
* inhibits viral RNA guanylytransferase and methyltransferase=fucked 5'-cap and cnat translate efficiently
* enahnces TH1 cell mediated immunity
172
lymphatic drainage--above and below pectinate lines
* internal hemorrhoids
* visceral innervation=NOT PAINFUL
* lymphatic drainage to internal iliac LN
* external hemorrhoids (below pectinate line)
* somatic innervation (inferior rectal branch of pudendal nerve)=PAINFUL if thrombosed
* lymphatic drainage to superficial inguinal nodes
173
provide an example of polycistronic mRNA
* bacterial lac operon-codes for the proteins necess for lactose metabolism by E. coli
* transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements
174
components of the lac operon
* regulatory gene
* promoter region
* operator region
* z gene-codes for beta galactosidase
* responsible for hydrolysis of lactose to glucose and galactose
* y gene-codes for permease=transmembrane enzyme that INC the permeability of the cell to lactose
* a gene encodes a beta-galactoside transacetylase--transfers acetyl groups to beta-galactosides and is unnecess for lactose metab by E. coli
175
what is the rate-limiting step in the synthesis of bile acids
cholesterol 7-alpha hydroxylase
176
IL-10
* anti-inflamm properties
* reduces production of:
* pro-inflamm TH1 cytokines (IL-2 and interferon gamma)
* MHC2 expression
* inhibits activated DC and macrophages
* causes attenutation of cellular-mediated immunity with some enhancement of humoral resp=protective effect of Crohns
177
spleen
* mesodermal origin (dorsal mesentery)
* supplied by splenic artery (branch of major foregut vessel, the celiac trunk)
* NOT a foregut deriv
* intraperitoneal organ
* mc intra-abdo organ injured d/r blunt trauma
178
Where does iron absorption predominantly occur
* duodenum and proximal jejunum
* bypass of this by gastrojejunostomy=iron deficiency anemia
179
where is abscorbic acid (vit c) absorbed?
* distal small bowel through an active process
180
where is pyroxidine (vit B6) absorbed
J and I by passive diffusion
181
Where are B7 (biotin) and B5 (pantothenic acid) absorbed
small and large intestine via the sodium-dependent multivitamin transporter
182
interferon gamma business
* inherited defects involving interferon gamma signaling pathway=disseminated mycobacterial dz in infany or early childhood
* pts require lifelong tx with anti-mycobacterial agents
183
Portocaval anastomoses!!!
* esophageal varices (clinical manifestation)
* portal circulation: left gastric vein
* systemic circulation: esophageal vein
* hemorrhoids
* superior rectal vein
* middle an dinferior rectal veins
* caput medusae
* paraumbilical veins
* superficial and inferior epigastric veins
184
what is the most severe and mc form of galactosemia
* GALT (galactose-1-phosphate uridyl transferase) deficiency
* symptoms within first few days of life after initiation of breastfeeding or formula:
* vomiting
* jaundice
* hepatomegaly
* lethargy
* xs galactose is converted to galactitol by aldose reductase-cataract from xs galactitol deposition in the lens
* (Galactokinase deficiency-less common type of galactosemia=only cataract formation)
185
annular pancreas
* pancreatic tissue encircling descending duodenum
* pathophys: failure of ventral pancreatic bud to properly migrate and fuse with the dorsal bud during the seventh and eighth wk of fetal development
* usually asymptomatic but may present with duodenal obstruction or pancreatitis
186
what are the two mc causes of SCID
* 1: X-linked
* 2: ADA (adenosine deaminase deficiency)
* deaminates adenosine to inosine in first step of elimination of xs adenosine from the cell
* adenosine accumulation is toxic to lymphocytes, leads to widespread death of T and B lymphocytes
* SCID: vulnerable to INC infections by bacteria, virus, fungi
* tx: BM transplantation
187
TEF + esophageal atresia CP
* excessive drooling
* occasional coughing
* cardiac, resp, abdo exam nml
* with attempted breast-feeding: several bouts of coughing and peri-oral **cyanosis** w/ o2 sat of 85% on rm air
* d/t reflux of breastmilk/formula and aspiration into the trachea/lungs
* PP: failure of primitive foregut to separate from the AW
188
Kehr sign
* any **abdo process** (ruptured spleen, peritonitis, hemoperitoneum) irritating the phrenic nerve sensory fibers a/r the diaphragm can cause referred pain to the C3-C5 **shoulder region**
189
Which drugs are most effective for motion sickness prevention
* anti-muscarinic agents and anti-histamines with anti-muscarinic action
* anti-cholinergic SE are common:
* blurry vision
* dry mouth
* urinary retention
* constipation
190
Lynch Syndrome and Mismatch repair
* Lynch syndrome=AD dz caused by abnml nucleotide mismatch repair
* mismatch repair system involves several genes: MSH2 and MLH1--code for components of human MutS and MutL homologs
* muts in these TWO genes accounts for approx 90% of cases of Lynch syndrome
BOARDS!
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