GI Tract Flashcards

1
Q

What are aphtous ulcers?

A
  • painful superficial ulceration of oral mucosa

- stress induced, resolves spontaneously, often recurrs

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2
Q

How can one ID an aphtous ulcer

A

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

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3
Q

what is behcet’s syndrome?

A

recurrent aphtous/genital ulcers, uveitis

  • immune complex vasculitis : small vessels
  • can be seen after viral infxn
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4
Q

What do oral herpes look like?

A

shallow, painful, red ulcers

- HSV 1 associated

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5
Q

When is the primary oral herpes infxn usually?

A
  • childhood
    Virus stays dormant in ganglia of trigeminal nerve
  • stress/ sunlight cause reactivation of virus
  • vesicles often arise on lips (cold sores
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6
Q

What are the risk factors for SCC of mouth?

A

tobacco and EtOH

- floor of mouth is a common location

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7
Q

What are precursor lesions for SCC of mouth?

A

Leukoplakia or erythoplakia

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8
Q

What is leukoplakia?

A

white plaque

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9
Q

What is hairy leukoplakia due to?

A

EBV
hairy, shaggy on lateral tongue
- ICPs
only hyperplasia

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10
Q

What is erythroplakia

A

Red plaque due to angiogenesis

- more suggestive of squamous dysplasia

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11
Q

What is the primitive gut tube made up of?

A
  • incorporates yolk sac during development
  • endoderm: epithelial lining of mucosa
  • mesdoerm - all other layers
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12
Q

What are the divisions of the GI tract?

A
  1. foregut = pharynx to duodenum
  2. Midgut - duodenum to transverse colon
  3. Hindgut = distal transverse colon to rectum
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13
Q

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

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

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14
Q

What is gastroschisis?

A

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

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15
Q

What is omphalocele?

A

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

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16
Q

What are other things than an omphalocele associated w/?

A

Beckwith Wiedemann syndrome
Chromosomal abnormaliity
congenital heart dz

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17
Q

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

A
vascular accident (apple peel atresia)
- bilious vomiting
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18
Q

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

A
  1. distended bowl proximal to atresia

2. absence of air distal to atresia

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19
Q

What are the steps for midgut development?

A

6th wk = midgut herniates thru umbilical range

10th wk = returns to abdominal cavity and rotates around SMA

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20
Q

What is the most common esophagus anomaly?

A

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

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21
Q

What is the clinical presentation of trachesophageal fistula?

A

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
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22
Q

What is the clinical test to dx trachesophageal fistula?

A

failure to pass NG tube into stomach

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23
Q

What is a H type esophagus anomaly?

A

fistula alone

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24
Q

What is seen on CXR of a pure esophageal atresia?

A

gasless abdomen

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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