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1

What are aphtous ulcers?

- painful superficial ulceration of oral mucosa
- stress induced, resolves spontaneously, often recurrs

2

How can one ID an aphtous ulcer

grayish base surrounded by erythema. the gray base represents granulation tissue

3

what is behcet's syndrome?

recurrent aphtous/genital ulcers, uveitis
- immune complex vasculitis : small vessels
- can be seen after viral infxn

4

What do oral herpes look like?

shallow, painful, red ulcers
- HSV 1 associated

5

When is the primary oral herpes infxn usually?

- childhood
Virus stays dormant in ganglia of trigeminal nerve
- stress/ sunlight cause reactivation of virus
- vesicles often arise on lips (cold sores

6

What are the risk factors for SCC of mouth?

tobacco and EtOH
- floor of mouth is a common location

7

What are precursor lesions for SCC of mouth?

Leukoplakia or erythoplakia

8

What is leukoplakia?

white plaque

9

What is hairy leukoplakia due to?

EBV
hairy, shaggy on lateral tongue
- ICPs
only hyperplasia

10

What is erythroplakia

Red plaque due to angiogenesis
- more suggestive of squamous dysplasia

11

What is the primitive gut tube made up of?

- incorporates yolk sac during development
- endoderm: epithelial lining of mucosa
- mesdoerm - all other layers

12

What are the divisions of the GI tract?

1. foregut = pharynx to duodenum
2. Midgut - duodenum to transverse colon
3. Hindgut = distal transverse colon to rectum

13

What are some development defects of anterior abdominal wall due to failure of...
a) rostral fold closure
b) lateral fold closure
c) caudal fold closure

a) sternal defects
b) omphalocele, gastroschisis
c) bladder exstrophy

14

What is gastroschisis?

extrusion of abdominal contents through lateral abdominal folds; not covered by peritoneum. hernia is right to umbilicus

15

What is omphalocele?

persistence of herniation of abdominal contents into umbilical cord, covered by peritoneum and amnion of umbilical cord

16

What are other things than an omphalocele associated w/?

Beckwith Wiedemann syndrome
Chromosomal abnormaliity
congenital heart dz

17

What are jejunal, ileal, and colonic atresia due to?

vascular accident (apple peel atresia)
- bilious vomiting

18

What is seen on x-ray for the small and large bowel atresias?

1. distended bowl proximal to atresia
2. absence of air distal to atresia

19

What are the steps for midgut development?

6th wk = midgut herniates thru umbilical range
10th wk = returns to abdominal cavity and rotates around SMA

20

What is the most common esophagus anomaly?

esophageal atresia w/ distal tracheoesophageal fistula due to malformation of trachesophageal septum

21

What is the clinical presentation of trachesophageal fistula?

drooling, choking, and vomiting w/ first feeding
- allows air to enter stomach (visible on CXR)
- cyanosis is secondary to larngospasm (to avoid reflux related aspiration)
- polyhydraminos b/c can't digest amniotic fluid

22

What is the clinical test to dx trachesophageal fistula?

failure to pass NG tube into stomach

23

What is a H type esophagus anomaly?

fistula alone

24

What is seen on CXR of a pure esophageal atresia?

gasless abdomen

25

What is congenital pyloric stenosis?

- hypertrophy of pylorus causes obstruction
- palpable olive mass in epigastric region and nonbilious projectile vomiting at 2 wks of age

26

What is Rx for congenital pyloric stenosis?

surgical incision

27

who is congenital pyloric stenosis common in?

first born males

28

What is the pancreas derived from?

foregut

29

What makes up the components of the pancreas?

Ventral pancreatic bud and dorsal pancreatic bud

30

What does the ventral pancreatic bud form?

pancreatic head and main pancreatic duct
uncinate process

31

What does the dorsal pancreatic bud form?

body, tail, isthmus, and accessory pancreatic bud

32

What is annular pancreas?

ventral pancreatic bud abnormally encircles 2nd part of duodenum
- forms a ring of pancreatic tissue that may causes duodenal narrowing
2/3 pts usually Asx

33

What is associated a/ infantile annular pancreas?

polyhrdraminos, Down's, esophageal and duodenal atresia, imperforate anus, Meckel's diverticulum

34

What is associated w/ adult annular pancreas?

ab pain, postprandial fullness, nausea, peptic ulceration, pancreatitis

35

What is pancreas divisum?

ventral and dorsal parts fail to fuse at 8 wks
- MC pancreatic congenital anomaly
- usually Asx
- drainage is preserved via major/minor papillae

36

What are signs/symptoms of pancreas divisum?

occurs when orifice of minor papillae inadequately drains the accessory ducts
- recurrent pancreatitis

37

What does the spleen arise from?

arises in mesentery of stomach (mesodermal) but is supplied by foregut (celiac artery)

38

What are the retriperitoneal structures?

- include GI structures that lack a mesentery and non GI structures.
SAD PUCKER
Suprarenal glands
Aorta and IVC
Duodenum (2nd and 3rd part)
Pancreas (except tail)
Ureters
Colon (descending and ascending)
Kidneys
Esophagus (lower 2/3)
Rectum (lower 2/3)

39

What is the parietal peritoneum innervated by?

intercostal, ilioinguinal, and iliohypogastric nerves
- sensitive and somatic pain = focal region of pain

40

What communicates w/ the lesser and greater sac in the GI tract?

omental foramen aka epiploic foramen of Winslow

41

What does the falciform ligament connect?

liver to anterior abdominal wall
- divides liver into 2 lobes

42

What is contained in the falciform ligament?

ligamentum teres hepatis (derivative of fetal umbilical vein)

43

What does the hepatoduodenal ligament connect?

liver to duodenum

44

What does the hepatoduodenal ligament contain?

portal triad thus ligament can be compressed b/w thumb and index finger to control bleeding.

45

What does the gastrohepatic ligament connect?

liver to lesser curvature of stomach
- may be cut during surgery to access lesser sac
- separates greater and less sac on the right

46

What does the gastrophepatic ligament contain?

gastric arteries

47

What does the gastrocolic ligament connect and contain?

- greater curvature to transverse colon
- gastroepiploic arteries
- parter of greater omentum

48

What does the gastrosplenic ligament connect and contain?

- greater curvature to spleen
- contains short gastric, left gastroepiploic vessels
- separates greater and lesser sac on left

49

What does the splenorenal ligament connect and contain?

spleen to posterior abdominal wall
- contains splenic artery and vein, tail of pancreas

50

What happens during the early development of the GI tract?

1. dorsal embryonic mesentery - suspends all guts from dorsal body wall
2. ventral embryonic mesentery - suspends foregut from ventral body wall
3. visceral developement: spleen, pancreas, liver and biliary structures develop w/in mesentery

51

What are the layers of the digestive tract?

MSMS
1. Mucosa
2. Submucosa
3. Muscularis externa
4. Serosa

52

What makes up the mucosa of the GIT?

epithelium (absorption)
lamina propria (support) - loose CT
muscularis mucosa (motility) - thin SM

53

What makes up the submucosa of the GIT?

submucosal nerve plexus (meissner's) - loose CT, mucus secreting glands

54

What makes up the muscularis externa of the GIT?

includes myenteris nerve plexus (Auerbach"s) - peristalsis
- inner circular and outer longitudinal muscle layer

55

What makes up the serosa of the GIT?

when intraperitoneal called serosa
- when retroperitoneal called adventitia

56

How deep do ulcers extend? and erosions?

Ulcers- into submucosa, inner or outer muscular layer
Erosions - mucosa layer only

57

What are the frequencies of basal electric rhythm in the GIT?

1. stomach - 3 waves/min
2. Duodenum - 12 waves/ min
3. Ileum - 8-9 waves/min

58

What is the histology of the esophagus?

nonkeratinzed stratified squamous epithelium and mucous glands

59

What is the histology of the stomach?

gastric glands and pits, mucous glands, chief, parietal, and EE cells

60

What is the histology of the duodenum?

villi and microvilli increase absorptive surface, Brunner's glands in submucosa, crypts of Lierberkuhn, goblet, paneth and EE cells
- simple columnar epithelium

61

What is the histology of the jejunum?

villi, microvilli, goblet, paneth, and EE cells
- plicae circularies and crypts of Lieberkuhn
- simple columnar epithelium

62

What is the histology of the ileum?

- M cells
- Peyer's patches (lamina propria, submucosa)
- Plicae circulares (proximal ileum) and crypts of Lieberkuhn
- largest number of goblet cells in the small intestine to secrete Bicarb
- simple columnar epithelium

63

What is the histology of the colon?

crypts but NO villi
numerous goblet cells
absorptive cells, EE cells, lymphoid follicles
- Na/H20 reabsorption
K/ Bicarb secretion

64

What is the function of the GIT immune function?

- produce Vit K
- Assists digestion
- protect against overgrowth of pathogenic bacteria

65

What is the location of the esophagus?

mediastinum
behind trachea and left atrium
- enters abdominal cavity through esophageal hiatus of diaphragm at T10 level

66

What are the 4 narrow points of the esophagus?

1. at origin - pharynx
2. arch of aorta
3. left primary bronchiole
4. esophageal hiatus

67

Compare the muscles found in the esophagus?

upper 1/3 - skeletal muscle
lower 1/3 - smooth muscle
- middle 1/3 = mixed

68

What is the blood supply of the esophagus?

1. upper 1/3 = inferior thyroid artery branches
2. middle 1/3 = bronchial artery and aorta
3. lower 1/3 = inferior phrenic and left gastric artery branches

69

What is the venous drainage of the esophagus?

1. upper 1/3 = inferior thyroid veins
2. middle 1/3 = bronchial, azygos, and hemiazygos
3. portal venous system

70

What are the abdominal aorta branches?

1. Celia artery at T 12
2. Left inferior phrenic artery
3. SMA at L1
4. left middle suprarenral artery
5. renal arteries at L1
6. Gonadal arteries
7. IMA at L 3
8. Bifurcation of abdominal aorta at L4

71

What is SMA syndrome?

when transverse portion of duodenum is entrapped b/w SMA and aorta causing intestinal obstruction

72

What does the celiac artery supply?

foregut --> stomach to proximal duodenum, liver, gallbladder, pancreas, spleen (mesoderm)

73

What does the SMA supply?

midgut --> distal duodenum to proximal 2/3 of transverse colon

74

What does the IMA supply?

hindgut --> distal 1/3 of transverse colon to upper portion of rectum (above pectinate line)

75

How is the GIT innervated?

1. foregut - vagus and T12/L1 vertebral level
2. midgut - vagus and L1 vertebral level
3. hindgut - pelvic and L3 vertebral level

76

What is the referred pain for the GIT?

1 foregut - epigastric
2. midgut - umbilical
3. hindgut - hypogastric

77

What is the role of Paneth cells?

produce lysozymes/defensins to protect from pathogenic microorganisms, found at the base of crypts

78

What are the branches of celiac trunk?

common hepatic, splenic, left gastric

79

What are the branches of the common hepatic artery?

1. right gastric artery
2. hepatic artery proper
3. gastroduodenal artery ==> anterior superior pancreaticoduodenal and right gastroepiploic artery

80

What are some collateral circulations in the GIT?

1. superior epigastric (internal thoracic/mammary) and inferior epigastric (external iliac)
2. superior pancreaticoduodenal (celiac trunk) and inferior (SMA)
3. middle colic (SMA) and left colic (IMA)
4. superior rectal (IMA) and middle/inferior rectal (internal iliac)

81

What are the sites for the portosystemic anastomoses?

1. esophagus - esophageal varices
2. umbilicus - caput medusae
3. Rectum - internal hemorrhoids

82

What makes up the liver's dual blood supply?

1. 75% due to portal vein
2. 25% due to hepatic arteryy

83

What veins are involved in esophageal varices?

left gastric and esophageal veins

84

What veins are involved in caput medusae?

1. paraumbilical and superficial/inferior epigastric below the umbilicus
2. paraumbilical and superior epigastric/lateral thoracic above the umbilicus

85

What veins are involved in internal hemorrhoids?

superior rectal and middle/inferior rectal

86

What is TIPS ( transjugular intrahepatic portosystemic shunt)?

shunt exists b/w portal vein and hepatic vein percutaneously relieves portal HTN by shunting blood to systemic circulation

87

How does the liver develop?

- it's an outgrowth of foregut endoderm
- hepatic diverticulum enters vental mesentery

88

What does the embryonic liver differentiate into?

1. distally into liver and gall bladder
2. proximally into biliary duct system

89

What are hepatocytes?

- functionally polarized liver cells
- has multiple apical/basal surfaces
1. Apical surface is faces bile canaliculi
2. Basal surface is next to sinusoids

90

What is the space of Disse?

b/w capillary endothelial cells and hepatocytes

91

What is a kuffer cell?

specialized monocytes

92

What is an Ito cell (stellate cell)?

mesenchymal cells - store fat soluble vitamins

93

What are the different zones in the liver anatomy?

Zone 1 - periportal zone
Zone 2 - intermediate zone
Zone 3 - pericentral vein (centrilobular)

94

What zone in the liver is affected by viral hepatitis?

zone 1

95

What is the function of zone 1 in the liver?

oxidative functions and synthesis of proteins/cholesterol

96

What zone in the liver plays a role in glycolysis, lipogenesis, alcohol detoxification?

zone 3

97

What zone is affected 1st by ischemia?

zone 3

98

What zone is the site of alcoholic injury?

zone 3

99

what zone is most sensitive to toxic injury

zone 3

100

what zone contains the P450 system?

zone 3

101

What is a portal lobule in the liver?

- triangular structure
central vein at each corner
portal tract in center
bile flows from periphery to center

102

How do blood and bile flow in the liver?

1. blood flows from portal triad to central vein
2. bile flows from central vein to portal triad

103

What makes up the portal triad?

1. biel ductule
2. hepatic artery
3. portal vein

104

What is the function of the gall bladder?

- stores bile

105

What artery supplies the gall bladder?

cystic artery (branch of right hepatic artery)

106

What are the different parts of the pancreas bordered by?

1. uccinate process - crossed by SMA
2. neck - anterior to hepatic portal vein
3. body = left and anteriorly to aorta

107

What makes up the biliary tree?

1. The left and right hepatic duct connect to form the common hepatic duct
2. Common hepatic duct combines w/ the cystic duct to form the common bile duct
3. Common bile duct combines w/ main pancreatic duct to expel their contents at the ampulla of vater

108

What can cause obstruction of the common bile duct

gallstones at ampulla of Vater and in the common bile duct
- tumors that arise in head of pancreas

109

What does the femoral triangle contain?

femoral vein, artery, and nerve

110

what is the order of contents in the femoral region?

NAVEL from lateral to medial
- Nerve, artery, vein, empty, lymphatics

111

What is the femoral sheath?

fascial tube 3/4 cm below the inguinal ligament
- contains the femoral vein, artery, and canal (deep inguinal lymph nodes) but NOT femoral nerve

112

What are the border of the femoral triangle?

1. superior - inguinal ligament
2. laterally - sartorius muscle
3. medially - adductor longus muscle

113

What does the inguinal canal contain?

1. in women = found ligament of uterus
2. men = spermatic cord and contents

114

What is a diaphragmatic hernia?

abdominal structures enters the thorax
- may often occur in infants as a result of defective development of pleuroperitoneal membrane; complicated by lung hypoplasia
- most commonly a hiatal hernia

115

What is a hiatal hernia?

- stomach herniates upward through the esophageal hiatus of the diaphragm

116

What is a sliding hiatal hernia?

GE junction is displaced upward
- hourglass stomach

117

What is paraesophageal hernia?

- GE junction is normal
- fundus protrudes into the thorax

118

What is indirect inguinal hernia?

- goes thru the interal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum
- enters internal inguinal ring lateral to inferior epigastric artery

119

What does an indirect inguinal hernia take place in infants?

- due to failure of processus vaginalis to close ( can form hydrocele); much more in common in males

120

What does an indirect inguinal hernia follow?

the path of descent of testes
- covered by all 3 layers of the spermatic fascia

121

What is a direct inguinal hernia?

- goes thru Hesselbach's triangle
- bulges directly through the abdominal wall medial to inferior epigastric artery
- goes thru external inguinal ring only
- covered by external spermatic fascia

122

Who does a direct inguinal hernia occur in?

older men

123

How to remember the indirect and direct inguinal hernias?

MD's dont LIe:
Meidal to inferior epigastric artery = Direct
Lateral to inferior epigastric artery = Indirect

124

What is a femoral hernia?

- protrudes below inguinal ligament thru the femoral canal below and lateral to pubic tubercle
- more common in women

125

What is the leading cause of bowel incarceration?

femoral hernia

126

What is in the Hesselbach's triangle?

=inferior epigastric vessels
- lateral border of rectum abdominis
- inguinal ligament

127

Where is gastrin made?

G cells in antrum of stomach

128

What is the role of gastrin?

- increase gastric acid secretion
- increases growth of gastric mucosa
- increases gastric motility
- increases pepsinogen secretion

129

How is gastrin regulated?

1. increased by stomach distention/alkalinization, amino acids, peptides, vagal stimulation
2. decreased by stomach pH < 1.5

130

What AA are potent stimulators of gastrin?

Phe and Trp

131

Where is CCK made?

I cells in duodenum and jejunum

132

What is the role of CCK?

1. increase pancreatic secretion
2. Increases gallbladder contraction
3. decrease gastric emptying
4. increase sphinter of Oddi relaxation

133

How is CCK regulated?

increased by fatty acids and amino acids

134

What does CCK act on to play it's role in the GIT?

muscarinic pathways to cause pancreatic secretion

135

Where is secretin made?

S cells of duodenum

136

What is the role of secretin?

1. increase pancreatic bicarb secretion
2. decrease gastric acid secretion
3. increase bile secretion

137

How is secretin regulated?

1. increased by acid, fatty acids in lumen of duodenum

138

Where is somatostatin made?

D cells of pancreatic islets and GI mucosa

139

What is the role of somatostatin?

1. decrease gastric acid and pepsinogen secretion
2. decrease pancreatic and small intestine fluid secretion
3. decrease gall bladder contraction
4. decreased insulin and glucagon release

140

How is somatostatin regulated?

- increased by acid entering duodenum
- decreased by vagal stimulation

141

Where is glucose-dependent insulinotropic peptide made? GIP

K cells of duodenum and jejunum

142

What is the role of GIP?

Exocrine - decrease gastric H secretion
Endocrine - increase insulin release

143

How is GIP regulated?

increased by fatty acids, amino acids, and oral glucose

144

Where is vasoactive intestinal peptide made (VIP)?

parasympathetic ganglia in sphincters, gall bladders, small intestine

145

What is the role of VIP?

1. increase intestinal water and electrolyte secretion
2. increase relaxation of intestinal smooth muscle and sphincters

146

How is VIP regulated?

- increased by distention and vagal stimulation
- decreased by adrenergic input

147

What is a VIPoma?

non-alpha, non-beta islet cell pancreatic tumor that secretes VIP

148

What are the symptoms of VIPoma?

- copious watery diarrhea
- hypokalemia
- achlorhydria

149

What is the role of NO?

increase SM relaxation, including LES

150

What is the role of motilin?

produces migrating motor complexes by initiating myenteric motor complexes

151

Where is intrinsic factor made?

parietal cells in stomach

152

What is the role of intrinsic factor?

vitamin B12 binding protein (required for B12 uptake in terminal ileum)

153

What happens w/ autoimmune destruction of parietal cells?

chronic gastritis and pernicious anemia

154

Where is gastric acid made?

parietal cells in stomach

155

What is the role of gastric acid?

1. decreases stomach pH
2. protects against bacteria
3. activates pepsinogen

156

How is gastric acid regulated?

1. increased by histamine, Ach, and gastrin
2. decreased by somatostatin, GIP, low pH, PGs, secretin

157

Where is pepsin made?

chief cells in stomach for protein digestion

158

How is pepsin regulated?

- increased by vagal stimulation, local acid, and gastrin

159

Where is bicarb made in the GIT?

- mucosal cells in stomach, duodenum, salivary glands, pancreas, and Brunner glands in duodenum

160

How is bicarb regulated?

- increased by pancreatic and biliary secretion w/ secretin and by vagal stimulation

161

How is saliva production regulated?

by both SNS and PNS in the salivary glands
1. parotid gland - 25% of saliva volume; serous
2. submandibular - 70% of volume; mucinous and serous
3. sublinguinal - 5% of volume; mixed as well

162

What are the contents of saliva?

- amylase - digests starch
- bicard - neutralized bacterial acids
- mucins - lubricate fod
- lipase, lysozyme, defensins, lactoferrin, IgA, growth factors

163

What is the concentration of saliva normally?

hypotonic b/c of absorption of Na and Cl at low flow rates
- isotonic w/ higher flow rates

164

Where is the parotid gland located?

- surface of masseter muscle
- anterior to external auditory meatus
- cranial nerve 7 runs thru it but is innervated by V3

165

What is the content of gastric secretions?

- high in H, K and Cl, low in Na

166

How does vagal stimulation activate gastric acid release from parietal cells?

1. GRP stimulates G cells to release gastrin
2. acts on M3 receptor of parietal cell for Gq to increase Ca and activate HKATPase --> This can be blocked by Atropine

167

How does gastrin activate gastric acid release from parietal cells?

1. binds to CCKB receptor on and Gq to increase Ca and activated HKATPase
2. activates histamine release from ECL cells

168

How does histamine activate gastric acid release from parietal cells?

released from ECL cells and bind to H2 receptors via Gs to increase cAMP to activate HKATPase

169

How do PGs, misoprostol, and somatostatin inhibit release of gastric acid from parietal cells?

- they activate Gi and decrease cAMP levels

170

What is the main enzyme needed to set up the H and Cl secretion from parietal cell?

- Carbonic anhydrase
exchanged Bicarb fro Cl and causes alkaline tide in venous blood
- H is secreted by HKATPase

171

What happens to Brunner glands in PUD?

hypertrophy

172

What is the tonicity of pancreatic secretions?

isotonic
1. low flow - high in Cl
2. high flow - high in Bicarb

173

What pancreatic enzyme is going to do the following digestions?
1. starch
2. fat
3. protein

1. alpha-amylase
2. lipase, PLA2, colipase
3. proteases - trypsin, chymotrypsin, elastase, carboxypeptidases. secreted as proenzymes

174

What does trypsinogen do?

- converted to active trypsin and then activates teh other zymogens and creates more trypsinogen (positive feedback loop)

175

How is trypsinogen activated?

by enterokinase/enteropeptidase

176

What enzymes are involved in carbohydrate digestion?

1. salivary amylase
2. pancreatic amylase
3. oligosaccharide hydrolases

177

What is the role of salivary amylase?

hydrolyzes alpha 1,4 linkages to yield disaccharides (maltose and alpha-limit dextrins)

178

What is the role of pancreatic amylase

hydrolyzes starch to oligosaccharides and disaccharides. highest concentration in duodenal lumen

179

What is the role of oligosaccharides hydrolases?

- at brush border
- rate limiting step in carb digestion
- producces monosaccharides from olio/disaccharides
- lactases, sucrases, alpha-dextrinases, etc

180

How are carbs absorbed in the GIT?

1. only monosaccharides are absorbed by enterocytes (glu, gal, fru)
2. glucose and galactose taken up by SGLT1 (Na dependent)
3. Fructose taken up by facilitated diffusion by GLUT-5
- all transported to blood by GLUT-2

181

Where is Fe absorbed in the GIT?

- as Fe2+ in duodenum via ATPases

182

Where is folate absorbed in GIT?

- jejunum

183

Where is B12 absorbed in GIT?

- terminal ileum along w/ bile acids, requires IF

184

Where are TGs absorbed in GIT?

- small intestine as CM via pancreatic lipase then goes thru lacteals

185

Where does the net absorption of water take place in the GIT?

jejenum

186

What are Peyer's patches?

- unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum
- contain specialized M cells that take up Ag

187

What happens to B cells stimulated in germinal centers of Peyer's patches?

- differentiate into IgA secreting plasma cells, which ultimately reside in lamina propria
- IgA receives protective secretory component and is then transported across the epithelium to the gut to deal w/ intraluminal Ag

188

What is bile made up of?

bile salt (bile acids conjugated to glycine or taurine, making them water soluble); phospholipids, cholesterol, bilirubin, water, and ions

189

What is the E involved in the rate limiting step to make bile?

Cholesterol 7 alpha hydroxylase

190

What is the function of bile?

1. digestion/absorption of lipids and fat soluble vitamins
2. cholesterol excretion (body's only means of eliminating cholesterol)
3. antimicrobial activity via membrane disruption

191

What is the product of heme metabolism?

bilirubin - removed from blood by liver and conjugated w/ glucornate and excreted in bile

192

What are the steps of heme metabolism?

1. heme degraded to unconjugated bilirubin ( water insolube)
2. UCB binds to albumin and goes to liver
3. UDP glucuronosyltransferase conjugates the UCB so now water soluble
4. CB travels to gut and processed by bacteria to become urobilinogen
5. 80% of urobilinogen excreted in feces as stercobilin
6. 20% of urobilinogen undergoes enterohepatic cirulation and some excreted in urine as urobilin

193

What is the most common salivary gland tumor?

pleomorphic adenoma (benign mixed tumor)

194

How does a pleomorphic adenoma usually present?

- painless, mobile mass, circumscribed, recurs frequently b/c of irregular margins

195

What is a pleomorphic adenoma composed of?

cartilage and epithelium

196

What is a Warthin's tumor?

papillary cystadenoma lymphomatosum
- benign cystic tumor w/ germinal centers.
- 2nd MC tumor in salivary gland

197

What is the MC malignant tumor of salivary glands?

- mucoepidermoid carcinoma

198

What are the components of mucoepidermoid carcinoma?

- mucinous and squamous components

199

How does mucoepidermoid carcinoma present?

as a painful mass b/c of common involvement of the facial nerve

200

What is achalasia?

failure of relaxation of LES due to loss of myenteric plexus
- HIgh LES opening pressure and uncoordinated peristalsis --> progressive dysphagia to solids and liquids

201

How can one Dx achalasia?

- barium swallow shows dilated esophagus w/ an area of distal stenosis
Bird's beak

202

When are some causes of secondary achalasia?

Chagas dz, Scelroderma (CREST syndrome)

203

What else is achalasia associated w/?

increased risk of esophageal SCC

204

What are risk factors for GERD?

EtOH, tobacco, obesity, fat rich diet, caffeine, hiatal hernia,

205

What are the common clinical findings of GERD?

heartburn and regurgitation due to decrease in LES tone upon lying down
- may also present w/ nocturnal cough and dyspnea, adult onset asthma,

206

What is esophageal varices?

painless bleeding of dilated submucosal veins in lower 1/3 of esophagus secondary to portal HTn
- MCC of death in cirrhois

207

What is esophagitis?

- associated w/ reflux, infxn, or chemical ingestion

208

What are the infxn related to esophagitis?

1. Candida - white psuedomembrane
2. HSV 1- punched out ulcers
3. CMV - linear ulcers

209

What is Mallory Weiss syndrome?

- mucosal lacerations at GEJ due to severe vomiting
- leads to painful hematemesis
- usually found in alcoholics and bulimics

210

What is BoerHaave Syndrome?

transmural esophageal rupture due to violent retching
- related to pneumothorax

211

What is esophageal strictures?

associated w/ lye ingestion and acid reflux

212

What is Plummer-Vinson syndrome?

1. Dysphagia due to esophageal webs
2. glossitis
3. Iron deficiency anemia

213

What are esophageal webs?

- thin protrusion of esophageal mucosa often in upper esophagus
- increase risk of SCC

214

What infxn is known to infame parotid gland?

- Mumps ; also causes orchitis, pancreatitis, aseptic meningitis, serum amylase increased

215

What are causes of sialadenitis?

MCC is obstructing stone leading to S. Aureus and Strep Viridans infxn
- usually unilateral

216

What is Barrett's esophagus?

- Glandular metaplasia: replacement of nonkeratinized stratified squamous epithelium w/ intestinal epithelium in the distal esophagus
- due to chronic GERD

217

what can Barrett's esophagus be associated w?

esophagitis, esophageal ulcers, and increased risk of esophageal adenocarcinoma

218

What cancers arise in the esophagus?

1. upper 2/3 = squamous
2. lower 1/3 = adenocarcinoma

219

What are the risk factors for esophageal SCC?

achalasia, alcohol, tobacco, Zenker's diverticula, esophageal webs, hot liquids (china and iran)

220

What are the risk factors for adenocarcinoma SCC?

Barrett's esophagus, tobacco, fat (obesity), GERD

221

What is the lymph node drainage of the esophagus?

1. upper 1/3 = cervical
2. middle 1/3 = mediastinal or tracheobroncial
3. lower 1/3 = celiac and gastric

222

What are the symptoms of malabsorption syndromes?

- diarrhea, steatorrhea, wt loss, weakness, vitamin and mineral deficiencies

223

What is tropical sprue?

- unknown cause but responds to antibiotics
- can affect entire small bowel
- arises after infectious diseases

224

What is Whipple's Disease?

- infxn w/ Tropheryma whipplei (gram posiitve) - PAS stain

225

What are the symptoms of Whipple's Dz?

- cardiac symptoms
- arthralgias
- neurologic symptoms are common

226

What is the histology of Whipple's Dz?

PAS positive foamy macrophages in intestinal lamina propria

227

What is the treatment for Whipple's Dz?

- IV Abx for 1 day
TMP-SMX for 1 year

228

What Abs are found in Celiac dz?

AutoAbs to gliadin, endomysial, transglutaminase

229

What is the histology of Celiac dz?

- blunting of villi
- lymphocytes in lamina propria (intraepithelially)
- crypt hyperplasia

230

What area of the GIT is commonly affected in Celiac dz?

distal duodenum

231

What are the HLA associations of Celiac dz?

DQ2 and DQ8

232

What is associated w/ Celiac sprue?

1. Dermatits Herpetiforms - due to IgA deposition at tip of dermal papillae
- resolves w/ gluten free diet
2. moderately increased risk of malignancy - T cell lymphoma

233

What is the pathogenesis of celiac dz?

- deamidated gliadin is presented by APCs via MHC II
-helped T cells mediate tissue damage

234

What is the most common disaccharidase deficiency?

lactase deficiency --> milk intolerance
- osmotic diarrhea
- abdominal distention

235

What does acquired disaccharidase deficiency arise from?

aging and GI infxn

236

How do you dx lactose tolerance test?

positive for lactase deficiency if
1. admin of lactose produces symptoms
2. glucose rises < 20 mg/dl

237

Histology of disaccharidase deficiency?

- normal appearing villi

238

What is abetalipoproteinemia?

- decreased synthesis of apolipoprotein B --> inability to generate CM --> decreased secretions of cholesterol, VLDL into bloodstream --> fat accumulation in enterocytes

239

When does abetalipoproteinemia present?

in childhood w/ malabsorption and neurologic manifestations

240

What are causes of pancreatic insufficiency?

- CF, obstructing cancer, chronic pancreatitis

241

What are malabsorption syndromes?

1. tropical sprue
2. Whipple's Dz
3. Celiac sprue
4. Disaccharidase deficiency
5. Abetalipoproteinemia
6. Pancreatic insufficiency

242

What cancer is found above the pectinate line? below?

above- adenocarcinoma
below - SCC

243

What type of hemorrhoids are found above the pectinate line? below?

above - internal
below - external

244

What is the arterial supply above the pectinate line? below?

above - superior rectal artery (branch of IMA)
below- inferior rectal artery (branch of internal pudendal artery)

245

What is the venous drainage above the pectinate line? below?

above - superior rectal vein --> IM vein --> portal system
below - inferior rectal vein --> internal pudendal vein --> internal iliac vein --> IVC

246

What is the embryologic germ layer above the pectinate line? below?

above - mesoderm
below - ectoderm

247

Why are internal hemorrhoids not painful?

b/c of visceral innervation and are therefore not painful

248

Why are external hemorrhoid painful?

b/c of somatic innervation from the inferior rectal branch of pudendal nerve

249

What is the lymphatic drainage above and below the pectinate line?

- above - deep nodes
below - superficial inguinal nodes

250

What are common causes of acute gastritis (erosive)?

- NSAIDS (decrease PGE1 = decreased gastric mucosa protection)
- Alcohol
- Uremia
- Burns (Curling's ulcer - decreased plasma volume --> sloughing of gastric mucosa)
- brain injury due to increased intracranial pressure (Cushing's Ulcer --> increased vagal stimulation --> increased Ach --> increased H production)

251

What are causes of chronic gastritis?

1. Type A - autoimmune mediated (10%)
2. Type B - H. Pylori meidated (90%)

252

Where is type A and type B chronic gastritis found in the GIT?

1. Type A = fundus/body
2. Type B = antrum

253

What is the MCC of vitamin B12 deficiency?

Type A chronic gastritis due to autoAbs to parietal cells - lack of IF

254

What findings are associated w/ Abs to parietal cells?

- Pernicious anemia and Achlorhydria

255

What is the consequence of achlorhydria in pernicious anemia?

- low acid production leads to increased gastrin levels and antral G cell hyperplasia

256

How does H. pylori cause chronic gastritis?

- urease and proteases weaken mucosal defenses b/c of virulence factors that penetrate through mucus layer and cause damage

257

What cancer is at increased risk due to H. pylori?

MALT lymphoma and gastric adenocarcinoma

258

What dz is associated w/ gastric hypertrophy w/ protein loss, parietal cell atrophy, and increased mucus cells?

Menetrier's dz - precancerous. Rugae of stomach are so hypertrophied that they look like brain gyri

259

What is the most common stomach cancer?

adenocarcinoma - early aggressive local spread and node/liver mets. often presents w/ acanthosis nigricans

260

What is intestinal adenocarcinoma causative agents?

- H pylori
- dietary nitrosamines (smoked foods)
- achlorhydria
- chronic gastritis
- type A blood

261

What is the location of intestinal adenocarcinoma on the stomach?

lesser curvature, looks like an ulcer w/ heaped up margins and non-radiating rugal folds

262

What is diffuse type stomach cancer?

- not assoicated w/ H pylori
- signet ring cells
- stomach wall grossly thickened and leathery (linitis plastica)

263

What are the lymph nodes mets associated w/ stomach cancer?

- Virhchow's node
- Sister Mary Joseph's nodule

264

What is Virchow's node?

- left supraclavicular node by metastasis from stomach

265

What is Sister Mary Joseph's nodule?

- subcutaneous periumbilical metastasis

266

Name this finding: bilateral metastases to ovaries w/ abundant mucus and signet ring cells?

Krukenberg's tumor

267

Where are ulcers seen in PUD?

1. gastric - 10%, distal
2. Duodenal - 90%

268

What are the characteristics of gastric ulcers?

1. pain greater w/ meals= wt loss
2. 70% due to H pylori infxn
3. caused by decreased mucosal protection against gastric acid and NSAIDS
4. increased risk of carcinoma
5. often occurs in older pts

269

What are the characteristics of duodenal ulcers?

1. pain decreases w/ meal = wt gain
2. 100% due to H pylori
3. caused by decreased mucosal protection or increased gastric acid secretion (ZE syndrome)
4. generally benign and no increase in cancer
5. Hypertrophy of brunner glands

270

What are the characteristics of a benign ulcer?

- small, punched out, flar margins

271

What are the characteristics of a malignant ulcer?

- irregular, larger, piling up of mucosa

272

What are complications of PUD?

1. Hemorrhage - gastric, duodenal (posterior > anterior): on lesser curvature bleeding from left gastric. Posterior bleeding from gastroduodenal artery
2. perforation - duodenal (anterior> posterior)

273

What is the classic presentation of IBD?

young female w/ recurrent bloody diarrhea and ab pain
- more prevalent in west especially whites and E. european jews

274

What is the location of Crohn's dz in the GIT?

- any portion of the GIT usually the terminal ileum and colon. Skips lesions and rectal sparring

275

What is the location of ulcerative colitis in the GIT?

- colon inflammation that starts at rectum and is continuous so no skip lesions

276

What is the gross morphology of Crohn's Dz?

- transmural inflammation
Cobblestone mucosa, creeping fat, bowel wall thickening (string sign on barium swallow x-ray), linear ulcers, fissures, fistulas

277

What is the gross morphology of ulcerative colitis?

mucosal and submucosal inflammation only.
- friable mucosal pseudopolps w/ freely hanging mesentery
- loss of haustra - lead pipe appearance

278

What is the microscopic morphology of Crohn's dz?

- noncaseating granuloma
- lymphoid aggregates (Th1 mediated)

279

What is the microscopic morphology of ulcerative colitis?

- crypt abscesses and ulcers, bleeding, no granulomas (Th2 mediated)

280

What are complications of Crohn's dz?

- strictures, fistulas, perianal dz, malabsorption, nutritional depletion, CRC, oxalate stones

281

What are complications of Ulcerative colitis?

- malnutrition, sclerosing cholagnitis, toxic megacolon, CRC (wrose w/ right sided colitis and pancolitis)

282

What are the intestinal manifestations of Crohn's and ulcerative colitis?

- Crohn's: diarrhea that may/may not be bloody
- UC: bloody diarrhea

283

What are the extraintestinal manifestations of Crohn's dz?

- migratory polyarthritis, erythema nodosum, ankylosing spondylitis, uveitis, kidney stones

284

What are the extraintestinal manifestations of Ulcerative colitis?

- pyoderma gangrenosum, primary sclerosing cholangitis, ankylosing spondylitis, uveitis, P-ANCA

285

What is the treatment for Crohn's dz?

Steroids, azathioprine, MTX, infliximab, adalimumab, S-ASA agents for mild dz

286

What is the treatment for ulcerative colitis?

ASA preparations (sulfasalazine) , 6MP, infliximab, colectomy can be curative

287

What are the smoking associations of Crohn's and UC?

- Crohn's: smoking increases risk
- UC: smoking is protective

288

What are the symptoms of Irritable bowel syndrome?

- recurrent abdominal pain associated w/ at least 2 of the following symptoms
1. pain improves w/ defecation
2. change in stool frequency
3. change in appearance of stool
4. bloating, flatulence, and change in bowel habits
5. diarrhea, constipation or alternating symptoms.

289

How do you dx irritable bowel syndrome?

- dx of exclusion: check TSH, CBC, ESR, stool leukocytes
- everything will be normal: no structural abnormality, chronic symptoms

290

What is the goal of Rx w/ irritable bowel syndrome?

treat symptoms

291

What is the cause of appendicitis?

- acute inflammation of appendix due to obstruction by fecalith (in adults) or lymphoid hyperplasia in kids

292

What are the findings for appendicitis?

- initial diffuse periumbilical pain that migrates to McBurney's point.
- Nausea, fever, may perforate and cause peritonitis
- guarding and rebound tenderness

293

What is the location of McBurney's point?

1/2 the distance from anterior superior iliac spine to umbilicus

294

What is a diverticulum?

a blind pouch protruding from the alimentary tract that communicates w/ lumen of the gut
- most are acquired and false in taht they lack or have an attenuated muscularis externa.

295

What is the MC location of diverticulum?

sigmoid colon

296

What is the difference btw and true and a false diverticulum?

True - all 3 gut layers outpouch
False - only mucosa and submucosa outpouch, occur especially where vasa recta perforate muscularis externa

297

What age group is diverticulosis common in?

- 60 yo and older

298

What is a diverticulosis caused by?

increased intraluminal pressure and focal weakness in colonic wall. Associated w/ low fiber diets.
- they are many false diverticula

299

What are the symptoms of diverticulosis?

- often asx or associated w/ vague discomfort
- common cause of hematochezia
- complications include diverticulitis and fistulas

300

What is diverticulitis?

- inflammation of diverticular classically causing LLQ pain, fever, leukocytosis
- may perforate to cause peritonitis, abscess formation, or bowel stenosis
- Give Abx

301

What has diverticulitis also been called?

left sided appendicitis due to overlapping clinical presentation

302

What is the treatment for diverticulitis?

- metronidazole, TMP-SMX, ciprofloxacin

303

What is Zenker's diverticulum?

- False diverticulum above the UES
- herniation of mucosal tissue at Killian's triangle b/w the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor

304

What are the presenting symptoms of Zenker's diverticulum?

- halitosis (due to trapped food particles), dysphagia, and obstruction

305

What is a traction diverticulum?

false outpouching near midpoint of esophagus

306

What is epiphrenic diverticulum?

false outpouching immediately above the LES

307

What is a Meckel's diverticulum?

- failure of vitelline duct to obliterate wk 5-6 of embryogenesis
- connection of gut lumen and umbilicius
- meconium drainage from umbilicus

308

What is associated w/ Meckels diverticulum?

- ectopic acid-secreting gastric mucosa and/or pancreatic tissue
- Melena, RLQ pain, intussuception, volvulus, or obstruction near the terminal ileum

309

What is the most common congential anomaly of the GIT?

- Meckel's diverticulum

310

How can you dx Meckel's diverticulum?

- pertechnetate study

311

What are the five 2's of Meckel's diverticulum?

- 2 inches long
- 2 ft from ileocecal valve
- 2% of population
- commonly presents in first 2 yrs of life
- many have 2 type of epithelia (gastric and pancreatic)

312

What causes telescoping of 1 bowel segment into distal segment commonly at the ileocecal junction?

- intussusception

313

What is seen w/ intussusception?

- currant jelly stools
compromise blood supply
- unusual in adults (associated w/ intraluminal mass or tumor)
- majority of cases w/ kids usually idiopathic, may be viral adenovirus

314

What is volvulus?

- twisting portion of bowel around its mesentery
- can lead to obstruction and infarction
- may occur at cecum - young adults
- at sigmoid - elderly
- USUALLY in elderly so think SIGMOID

315

What is a transmural small bowel infarction do to?

- embolism/thrombosis of SMA of thrombosis of mesenteric vein
- can be due to polycythemia vera, Atrial fibrillation, or vasculitis

316

What is a mucosal small bowel infarction do to?

- marked hypotension b/c furthest away from blood supply

317

What are clinical features of small bowel infarction?

ab pain, bloody diarrhea, deceased bowel sounds

318

What causes Hirschsprung's dz?

- congenital megacolon due to lack of ganglino cells/enteric nervous plexuses
- due to failure of neural crest cell migration

319

How does Hirschsprung's dz present?

- chronic constipation early in life
- dilated portion of colon proximal to the aganglionic segment (megacolon) resulting in transition zone
- involves rectum
- usually failure to pass meconium
- associated w/ Down's

320

What is ileus?

high pitched bowel sounds

321

What are symptoms of duodenal atresia?

- early bilious vomiting w/ proximal stomach distention
- shows up as double bubble on X-ray b/c of failure of recanalization of small bowel
- associated w/ Down's

322

What is meconium ileus found in?

- CF b/c meconium plug obstructs intestine preventing stool passage at birth
- Hirschsprung's dz

323

What is necrotizing enterocolitis?

- necrosis of intestinal mucosa and possible perforation
- colon is usually involved but can involved entire GI tract

324

In whom is necrotizing enterocolitis more common in?

preemies due to decreased immunity

325

What is ischemic colitis?

- reduction in intestinal blood flow causes ischemia
- Pain out of proportion w/ physical findings
- pain after eating = wt loss
- commonly seen as splenic flexure and distal colon
- typically affect elderly

326

What is the MCC cause of small bowel obstruction?

Adhesions - fibrous band of scar tissue; commonly forms after surgery

327

What is angiodysplasia?

- tortuous dilation of vessels causing hematochezia
- most often found in cecum, terminal ileum and ascending colon
- more common in old people

328

What are colonic polyps?

masses protruding into gut lumen
- 90% are non-neoplastic
- often found in rectosigmoid
- can be tubular or villous

329

What are precancerous colon polyps?

- adenomatous especially sessile and villous

330

Malignant risk of colon polyps are associated w/ what?

- increased size, villous histology, increased epithelial dysplasia

331

What are colon polyp symtpoms?

often Asx, lower GI bleed, partial obstruction, secretory diarrhea

332

What are hyperplastic colon polyps?

- MC non-neoplastic polyp
- serrated/stellate appearance

333

What are juvenile colon polyps?

- mostly sporadic lesions in kids less than 5
- 80% in rectum
- if single then no malignant potential
- when multiple then increased risk of adenocarcinoma

334

What is Peutz-Jegher syndrome?

- AD syndrome featuring multiple nonmalignant hamartomas thru-out GIT along w/ hyperpigmented mouth, lips, hands, gentalia
- associated w/ increased risk of CRC and other visceral malignancies such as breast, GYN, and other GI
- single polyps are not malignant

335

What mutation is Familial adenomatous polyposis associated w/?

- AD mutation of APC gene on chromosome 5q
- 2 hit hypothesis and 100% progress to CRC

336

Where are the polyps in FAP?

always involves rectum, thousands of polyps, pancolonic

337

What condition is known as FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium?

Gardner's syndrome

338

What condition is known as FAP + malignant CNS tumor?

Turcot syndrome

339

What CRC is associated w/ AD mutation of DNA mismatch repair genes?

- Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome)
- 80% progress to CRC and proximal colon is always involved

340

What other cancers are associated w/ HNPCC and Lynch syndrome?

- increased risk of ovarian and endometrial cancer

341

What are additional risk factor besides the genetics for CRC?

- IBD, tobacco use, large villous adenomas, juvenile polyposis syndrome, Peutz-Jeghers syndrome

342

What area of the colon is affected w/ CRC?

- rectosigmoid > ascending > descending

343

What type of lesion are seen w/ CRC in the ascending colon?

- Raised lesions usually = exophytic masses that cause Fe deficiency anemia and wt loss - usually a vague pain

344

What type of lesion are seen w/ CRC in the descending colon?

- Napkin-Ring lesion = infiltrating mass, partial obstruction, colicky pain, hematochezia

345

What bacteremia is associated w/ CRC?

Strep bovis

346

How can one Dx CRC?

1. Fe deficiency anemia in males (> 50) and postmenopausal females raises suspicion
2. Screen pts > 50 w/ colonscopy or stool occult blood test
3. Apple core lesions on barium enema x-ray
4. CEA tumor marker, good for monitoring recurrence, not useful for screening

347

What are the 2 molecular pathways that lead to CRC?

1. Microsatellite instability pathway (15%)
2. APC/Beta Catenin pathway (85%)

348

What is involved in the microsatellite instability pathway for CRC?

- DNA mismatch repair gene mutations --> sporadic and HNPCC symptoms.
- mutations accumulate but no defined morphologic correlates

349

What is involved in the adenoma- carcinoma sequence of CRC?

1. Normal colon initially but then a loss of APC gene = decreased intercellular adhesion and increased proliferation
2. Colon at risk then get KRAS mutation = unregulated intracellular signal transduction
3. Adenomas forms then acquires loss of P53 = increased tumorigenesis

350

What is the most common small bowel tumor?

- carcinoid tumor of neuroendocrine cells

351

What is the immunostain for carcinoid tumors?

- synaptophysin and chromogranin

352

What are the most common sites for carcinoid tumors?

- appendix, ileum, and rectum

353

What is seen on EM for carcinoid tumor?

dense core bodies on EM

354

What leads to carcinoid syndrome?

When the cancer has metastasized to the liver where it can no longer efficiently metabolize the 5HT w/ MAO.
- there are high levels of 5HT

355

What are the symptoms for carcinoid syndrome?

1. flushing
2. right side heart valve disease
3. wheezing due to bronchospasm
4. diarrhea

356

What is the treatment for carcinoid tumor?

1. resection
2. octreotide
3. somatostatin

357

What are the clinical effects of portal HTN?

1. esophageal varices
2. hematemesis
3. peptic ulcers
4. melena
5. splenomegaly
6. caput medusae, ascites
7. portal hypertensive gastropathy
8. hemorrhoids

358

What are the effects of liver cell failure?

1. coma, scleral icterus, fetor hepaticus (musty breath)
2. spider nevi
3. gynecomastia, jaundice, testicular atrophy
4. liver flap = asterixis (coarse hand tremor)
5. bleeding tendency (decreased clotting factors and increased PT time)
6. anemia and ankle edema

359

What is cirrhosis?

diffuse fibrosis and nodular regeneration destroys normal architecture of liver
- increased risk for HCC

360

what are the common causes of liver cirrhosis?

1. viral hepatitis
2. alcohol
3. biliary dz
4. hemochromatosis

361

What type of heart disease is associated w/ carcinoid tumor?

- right sided valvular fibrosis
- tricupsid regurg and pulmonary valve stenosis

362

What are the serum markers of liver pathology?

1. ALT and AST
2. ALP
3. GGT

363

What conditions are associated w/ increased ALT and AST?

1. Viral hepatitis - ALT > AST
2. Alcoholic hepatitis AST > ALT

364

What conditions are associated w/ increased ALP?

- obstructive liver disease (HCC), bone disease, and bile duct disease

365

What conditions are associated w/ increased GGT?

- increased in various liver and biliary dz like ALP but not in bone disease

366

What are serum markers for the pancreas?

- amlyase : increased in acute pancreatitis and mumps
- lipase : increased in acute pancreatitis

367

What is Reye's syndrome?

- rare, often fatal childhood hepatoencephalopathy
- due to giving kids ASA after a viral infxn

368

When is the only time to give ASA to kids?

Kawasaki's disease

369

What are the pathologic findings for Reye's syndrome?

1. mitochondrial abnormalities
2. fatty liver w/ microvesicular fatty change
3. hypoglycemia
4. vomiting
5. hepatomegaly
6. coma

370

What is the mechanism of damage for Reye's syndrome?

- aspirin metabolits decrease beta- oxidation by reversible inhibition of mitochondrial enzyme

371

What are initial signs of alcoholic liver disease?

hepatic steatosis - short term change w/ moderate alcohol intake
- macrovesicular fatty changes that may be reversible w/ alcohol cessation

372

What happens w/ sustained, long term consumption of alcoholic liver dz?

- alcoholic hepatitis - swollen and necrotic hepatocytes w/ neutrophilic infiltration
- mallory bodies (intracytoplasmic eosinophilic inclusions) are present

373

What is the irreversible form of alcoholic liver dz?

- alcoholic cirrhosis

374

What is seen w/ alcoholic cirrhosis?

- micronodular, irregularly shrunken liver w/ hobnail appearance.
- sclerosis around central vein (zone III)
- has manifestations of chronic liver disease (jaundice and hypoalbuminemia)

375

What is the fibrosis in liver cirrhosis mediated by?

- stellate cells via TGF-beta
- stellate cells are beneath endothelial cells that line the sinusoids

376

What are the symptoms of alcoholic cirrhosis?

1. portal HTN
2. decreased detoxification of metabolites - mental states changes, asterixis, coma all due to increased ammonia
3. decreased protein synthesis - monitor w/ PT

377

What are the symptoms of Acute viral hepatitis?

- jaundice (mixed CB and UCB) w/ dark urine, fever, malaise, and nausea

378

What happens to liver enzymes during acute viral hepatitis?

- ALT >> AST

379

What is seen in microscopic pathology of acute viral hepatitis?

- inflammation w/in portal tracts and w/in lobules of liver

380

What is the most common primary tumor of the liver?

HCC

381

What are risk factors for HCC?

1. Hep B and C
2. Wislon's dz
3. hemochromatosis
4. alpha1 antitrypsin deficiency
5. alcoholic cirrhosis
6. carcinogens such as aflatoxin from Aspergillus

382

What are the clinical findings for HCC?

1. jaundice
2. hepatomegaly
3. ascites
4. polycythemia
5. hypoglycemia

383

How does HCC commonly spread?

- hematogenous dissemination

384

What are some other liver tumors?

1. carvenous hemangioma
2. hepatic adenoma
3. angiosarcoma

385

What tumor is most common for the liver?

mets from stomach, pancreas, lung, colon, and breast
- they are multiple nodules in liver. Detected as hepatomegaly w/ nodules on free edge of liver

386

What is cavernous hemangioma?

- common, benign liver tumor
- typically occurs 30-50 yrs of age
- biopsy is contraindicated b/c of risk of hemorrhage

387

What is a hepatic adenoma?

- benign liver tumor associated w/ OCPS or steroid use
- can regress spontaneously
- there is a risk of rupture and intraperitoneal hemorrhage especially during pregnancy

388

What is an angiosarcoma?

- malignant tumor of endothelial origin; associated w/ exposure to arsenic and PVC

389

What happens to the liver when there is passive congestion of blood due to right sided heart failure and Budd- Chiari syndrome?

Nutmeg liver

390

What happens if a nutmeg liver's conditions persists?

- centrilobular congestion and necrosis can result in cardiac cirrhosis

391

What is Budd- Chiara syndrome?

- occlusion of IVC or hepatic vein w/ centrilobular congestion and necrosis, leading to congestive liver dz (hepatomegaly, ascites, abdominal pain, and eventual liver failure)

392

What is Budd- Chiari syndrome associated w/?

- hypercoaguable state, polycythemia vera, pregnancy, and HCC

393

What can develop w/ Budd-Chiari syndrome?

- varices and visible abdomina/back veins
- absence of JVD

394

What happens to the liver w/ alpha1 antitrypsin deficiency?

- misfolded gene products aggregate in hepatocellular ER leading to cirrhosis w/ PAS positive globules in liver

395

What happens to the lungs w/ alpha 1 antitrpsin deficiency?

- lack of functioning enzyme = decreased elastic tissue = panacinar emphysema

396

What is the basic cause of jaundice?

- yellow skin and/or sclera due to elevated bilirubin caused by direct hepatocellular injury, obstruction of bile flow, and hemolysis (extravascular) or ineffective erythopoiesis

397

What is associated w/ obstructed bile flow?

- gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites
- HLD, xanthomas, steatorrhea w/ malabsorption

398

What kind of bilirubin is elevated w/ hepatocellular damaged type jaundice?

- direct and indirect elevated
- increased urine bilirubin
- normal/decreased urine urobilinogen

399

What kind of of bilirubin is elevated w/ obstructive type of jaundice?

- direct
- increased urine bilirubin = dark urine
- decreased urine urobilinogen

400

What kind of bilirubin is elevated w/ hemolytic type of jaundice?

- indirect
- no urine bilirubin
- increased urine urobilinogen = dark urine b/c the UCB is converted to urobilinogen

401

What is the pathogenesis of physiologic neonatal jaundice?

- at birth, there are immature UDP-glucuronyl transferase --> UCB --> jaundice/kernicterus

402

Why does kernicterus happen w/ physiologic neonatal jaundice?

- b/c UCB is fat soluble and can deposit in teh basal ganglia leading to neurologic deficits and even death

403

What are the hereditary hyperbilirubinemia disorders?

1. Gilbert- UCB
2. Crigler Najjar - UCB
3. Dubin- Johnson - CB
- all are AR

404

What is Gilbert's syndrome?

- mildly decreased UDP-glucuronyl transferase or decreased bilirubin uptake
- elevated UCB w/ overt hemolysis, fasting, and stress
- Asx

405

What is Crigler-Najjar syndrome type I?

- absent UDP-glucuronyl transferase
- presents early in life and pts die w/in a few years

406

What are the findings of Crigler-Najjar syndrome type I?

- jaundice, kerniterus, increased UCB

407

What are the findings of Crigler-Najjar syndrome type II?

- less severe and responds to phenobarbital which increases liver enzyme synthesis

408

What is the treatment for Crigler-Najjar syndrome type I?

plasmaphereis and phototheraphy

409

What is Dubin-Jonhnson syndrome?

- CB b/c of defective liver excretion = grossly black liver
- benign

410

What is Rotor's syndrome?

- similiar to Dubin-JOhnson but even milder and does not cause black liver

411

What is the pathogenesis of Wilson's dz?

inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmis
- due to defect in copper transporting ATPase (ATP7B gene)
- AR (Ch13)

412

Where do copper accumulate in Wilson's dz?

- liver, brain, cornea, kidneys, and joints

413

What is Wilson's disease characterized by?

1. decreased ceruloplasmin, cirrhosis, corneal deposits leading to Kayser-Fleischer rings
2. HCC
3. hemolytic anemia
4. Basal ganglia degenerations (Parkinsonian symptoms)
5. Asterixis
6. Dementia, Dyskinesia, Dysarthria

414

What is the treament for Wilson's dz?

- pencillamine chelate coppers

415

What is the classic triad of hemochromatosis?

1. micronodular cirrhosis
2. DM - brittle
3. Skin pigmentation - bronzed

416

What is the pathogenesis of hemochromatosis?

- deposition of hemosidern (Fe)
- excess Fe deposition due to C282Y gene or H63D mutation on HFE gene
- associated a/ HLA-A3

417

What are other associations of hemochromatosis?

- CHF
testicular atrophy in males and increased risk of HCC

418

What are the primary and secondary causes of hemochromatosis?

Primary - AR - loss of HFE gene; loss of enterocyte mediated Fe absorption dependent on body demand
Secondary - chronic transfusion therapy

419

What are the lab findings for hemochromatosis?

increased ferritin, Fe, and increased saturation
- decreased TIBC

420

What is the treatment for hemochromatosis?

- phlebotomy, deferasirox, and deferoxamine

421

What is the pathogenesis for Primary biliary cirrhosis?

- autoimmune destruction of intraheptaic bile ducts ,lymphocytic infiltrate and granulomas
- think WOMEN aged 40

422

What is the pathogenesis of primary scleosing cholangitis?

- unknown cause of concentric onion skin bile duct fibrosis --> alternating strictures and dilations w/ beading of intra and extra hepatic bile ducts on ERCP
- think MEN

423

What is the patogenesis of secondary biliary cirrhosis?

- extrahepatic biliary obstruction (gallstones, biliary stricture, chronic pancreatitis, carcinoma of pancreatic head) --> increased pressure in intrahepatic ducts --> injury/fibrosis and bile stassis

424

What presents as pruritus, jaundice, dark urine, light stools, hepatosplenomegaly?

Secondary biliary cirrhosis
Primary biliary cirrhosis
Primary scleorsing cholangitis

425

What are the labs associated w/ PBC and PSC?

- increased CB
- increased cholesterol
- increased ALP

426

What antibodies is associated w/ Primary biliary cirrhosis?

- increased serum mitochondrial Abs including IgM
- associated w/ other autoimmune conditions (eg CREST, RA, and Celiac dz)

427

What is associated w/ Primary sclerosing cholangitis?

- Hypergammaglobulinemia (IgM)
- Associated w/ ulcerative colitis
- can lead to secondary biliary cirrhosis
- P-ANCA can be positive and there is an increased risk of cholangiocarcinoma

428

What is biliary atresia?

- failure to form extrahepatic biliary tree lumen
- leads to biliary obstruction w/in 1st months of life
- presents w/ Jaundice and progresses to cirrhosis due to CB
- icterus, clay colored stools, dark colored urine

429

What is ascending cholangitis?

- bacterial infxn of bile ducts
- usually due to ascending infxn w/ enteric gram negative bacteria
- presents as sepsis, jaundice, and abdominal pain
- increased incidence of choledocholithiasis

430

What are causes of gallstones?

- increased cholesterol and/or bilirubin
- decreased bile salts
- gall bladder stasis

431

What are the types of stones?

1. cholesterol - radiolucent w/ some califications
2. Pigment - radiopaque. Black = hemolysis. Brown = infxn

432

What diseases are associated w/ cholesterol stones?

- obesity, Crohn's, CF, advance age, cirrhosis, clofibrate, estrogens, multiparity, rapid wt loss, and Native American origin

433

What diseases are associated w/ pigment stones?

- chronic hemolysis, alcoholic cirrhosis, advanced age, and biliary infxn

434

What is biliary colic?

- neurohormonal activation triggers contraction of gallbladder, forcing a stone into cystic duct. may present w/out pain= waxing and waning RUQ pain

435

What are complications of gallstones?

- fistulas btw gallbladder and small intestine leading to air in the biliary tree
- can obstruct ileocecal valve

436

How do you dx gallstones?

- USG, radiouclide biliary scan (HIDA), cholescystectomy

437

What are the risk factors for gallstones?

1. Female
2. Forty
3. Fertile (pregnancy)
4. Fat

438

What is Charcot's traid of cholangitis?

- jaundice
- fever
- RUQ pain

439

What is a positive Murphy's sign?

- inspiratory arrest on deep RUQ palpation due to pain

440

What is cholecystitis?

- inflammation of gall bladder
- usually from gallstones, rarely ischemia of infxns (CMV)
- increased ALP if bile duct becomes involved

441

What is acute cholecystitis?

- RUQ pain that radiates to right scapula
- Fever w/ increased WBC, N/V
- risk of rupture if left untreated

442

What is chronic cholecystitis?

- due to chemical irriation from longstanding cholethiasis
- porcelain gallbladder = late complication
- dystrophic calcifications
- Rokitansky Aschoff sinus formation

443

What is the pathogenesis of acute pancreatitis?

- autodigestion of pancreas by pancreatic enzymes

444

What are causes of acute pancreatitis?

- gall stones, EtOH = main causes
- trauma, steroids, mumps, autoimmune dz, scorpion sting, hypercalcemia, Hyper TGs (>1000), ERCP, drugs

445

What are the labs for acute pancreatitis?

- elevated amylase, lipase
- hypocalcemia due to fat saponification

446

What are complications of acute pancreatitis?

- DIC, ARDS
- diffuse fat necrosis
- pseudocyst formation
- hemorrhage
- infxn
- multiorgan failure

447

What is the pathology of chronic pancreatitis?

- chronic inflammation, atrophy, calcification of pancreas, fibrosis of pancreas parenchyma
- islet damage

448

What are causes of chronic pancreatitis?

- Alcohol abuse and idiopathic
CF in kids

449

What can chronic pancreatitis lead to?

- pancreatic insufficiency --> steartorrhea, fat soluble vitamin deficiency, DM and increased risk of pancreatic adenocarcinoma

450

What are risk factors for pancreatic adenocarcinoma?

- tobacco use
- chronic pancreatitis
age >50
- Jewish and African American males

451

Tell me about pancreatic adenocarcinoma?

- prognosis averages 6 months of less
- very aggressive tumor arising from pancreatic duct
- usually already metastasized at presentation
- tumors are common in pancreatic head
- associated w/ CA19-9 and CEA

452

What does pancreatic adenocarcinoma usually present w/?

- abdominal pain radiating to back
- wt loss (due to malabsorption and anorexia)
- migratory thrombophlebitis - redness and tenderness on palpation of extremities (Trousseau's syndrome)
- obstructive jaundice w/ palpable, nontender gallbladder (courvoisier's sign)

453

What is the treatment for pancreatic adenocarcinoma?

Whipple procedure, chemotherapy, radiation therapy

454

What are the H2 blockers?

cimetidine, ranitidine, famotidine, nizatidine

455

what is the mechanism of the H2 blockers?

- reversible block of histamine H2 receptors --> decreased H secretion by parietal cells

456

What is the clinical use of H2 blockers?

- peptic ulcer, gastritis, mild esophageal reflux

457

What is the toxicity of H2 blockers?

1. Cimetidine - potent inhibitor of CYP450, decreases renal excretion of Creatinine, antiandrogenic effects (prolactin release, gynecomastia, impotence, decreased libido in males, can cross BBB (confusion, dizziness, headaches) and placenta
2. Ranitidine - decreases renal excretion of creatinine

458

What are the proton pump inhibitors?

Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole

459

MOA of PPIs?

irreversibly inhibits HKATPase in stomah parietal cells

460

Clinical use of PPIs

- peptic ulcer, gastritis, esophageal reflux, ZE syndrome

461

ADE of PPIs

- increased risk of C difficile infxns, pneumonia, hip fractures, decreased serum Mg w/ long term use

462

MOA of bismuth and sucralfate

- binds to ulcer base, providing physical protection and allowing Bicarb secretion to reestablish pH gradient in the mucous layer
- sucralfate needs acidic pH to function

463

clinical use of bismuth and sucralfate

increases ulcer healing, traveler's diarrhea

464

MOA of MIsoprostol

- PGE analog, increased production and secretion of gastric mucous barrier, decreased acid production

465

Clinical use of misoprostol

- prevention of NSAID induced peptic ulcers; maintenance of a patent ductus arteriosus
- also used to induce labor (ripens cervix)

466

ADE of Misoprostol

- diarrhea
- contraindicated in women of childbearing potential (abortifacient)

467

MOA of octreotide

- long acting somatostatin analog

468

clinical use of octreotide

- acute variceal bleeding, acromegaly, VIPoma, carcinoid tumor

469

ADE of octreotide

- nausea, cramps, steatorrhea

470

What are antacids used for?

- can affect absortion, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying
- all cause hypokalemia

471

What are the antacids?

- Al OH
- MgOH
- Ca carbonate

472

ADE of AlOH

- constipation and hypophosphatemia, proximal muscle weakness, osteodystrophy, seizures

473

ADE of MgOH

- diarrhea, hyporeflexia, hypotension, cardiac arrest

474

ADE of Ca carbonate

- hypercalcemia, rebound acid increase
- can chelate and decrease effectiveness of other drugs

475

What are some osmotic laxative?

- MgOH
- Mg citrate
- PEG
- lactulose

476

MOA of osmotic laxatives

- provide osmotic load to draw water out

477

what is the cinical use for osmotic laxatives

- constipation

478

clinical use for lactulose

- treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretions as Nh4

479

ADE of osmotic laxatives

- diarrhea, dehyrdation, may be abused by bulimics

480

MOA Infliximab

- TNF alpha mab

481

Clinical use for infliximab

- Crohn's disease, ulcerative colitis, RA

482

ADE infliximab

- infection (including reactivation of latent TB)
- fever
- hypotension

483

MOA of sulfasalazine

- combo of sulfapyridine (antibacterial) and 5 aminosalicylic acid (anti-inflammatory)
activated by colonic bacteria

484

clinical use of sulfazalazine

- ulcerative colitis and Crohns

485

ADE of sulfasalazine

- malaise, nausea, sulfonamide toxicity, reversible oligospermia

486

MOA of ondansetron

5HT antagonist, powerful centralacting antiemetic

487

Clinical use of ondansetron

- control vomiting postoperatively and in pts undergoing cancer chemotherapy

488

ADE of ONdansetron

headache, constipation

489

MOA of Metoclopramide

- D2 receptor antagonist, increase resting tone, contractility, LES tone, motilits
- does not influence colon transport time

490

clinical use of metoclopramide

- diabetic and post-surgery gastroparesis, antiemetic

491

ADE of metoclopramide

1. increase parkinsonian effect
2. restlessness, drowsiness, fatigue, depression, nausea, diarrhea
3. drug interaction w/ Digoxin and diabetic agents
4. contraindicated in pts w/ small bowel obstruction of Parkinson's disease

492

MOA of prokinetic agents of GIT

- increase Ach, increase 5HT, decrease D2

493

What are prokinetic agents?

1. Cholinergic agonists
2. AchE inhibitors
3. Domperidone - inhibits D2
4. Cisapride = 5HT agonist
5. Macrolide = stimulate 5HT motilin receptors