GI Deck 2 Flashcards
1
Q
What is the target of Ghrelin?
A
Hypothalamus
2
Q
Where is ghrelin produced?
A
Stomach/ proximal small bowel
3
Q
What ist he action of ghrelin?
A
Increases food intake
4
Q
Where is GLP1 produced?
A
Distal small bowel
5
Q
What is the target of GLP 1?
A
Stomach, pancreas
6
Q
What is the funciton of GLP 1?
A
Decrease gastric emptying, decrease food intake
7
Q
What is the target of PYY?
A
Stomach, Pancreas, CNS
8
Q
Where is PYY produced?
A
Distal small bowel
9
Q
What is the action of PYY?
A
Decrease gastric emptying
Decrease food intake
10
Q
What is the target of CCK?
A
Stomach, CNS
11
Q
WHere is CCK produced?
A
Proximal small bowel
12
Q
What is teh action of CCK?
A
Decreases gastric emptying
13
Q
What peptide correlates with fat/energy stores and is important in obesity?
A
Leptin - obese humans have high leptin levels so obesity is a state of leptin resistance
Leptin deficient mice are morbidly obese
14
Q
What are risk stratification measures for obesity (i.e. what defines Metabolic Syndrome)?
A
3 or more abnormal:
Central obesity
Blood pressure
Triglycerides
HDL cholesterol
Fasting Blood Glucose
15
Q
What diabetes medications promote weight gain?
A
Insulin
Sulfonylureas
Pioglitazone
16
Q
What depression medications increase weight?
A
Paroxetine
Amitriptyline
17
Q
What psychosis medicatiosn increase weight?
A
Olanzapine
Quietapine
18
Q
What antihypertensives increase weight?
A
β-blockers
19
Q
What contraceptives increase weight?
A
Depo-Provera
20
Q
What migraine medications increase weight?
A
Amitriptyline
21
Q
What Diabetic medicaitons are weight neutral?
A
Metformin
Exenatide
Liraglutide
Pramlintide
Canagliflozin
22
Q
What antidepressants are weight neutral?
A
Buproprion
Fluoxetine
23
Q
What antipsychotics are weight neutral?
A
Ziprasidone
24
Q
What antihypertensives are weight neutral?
A
Thiazide diuretics
ACE inhibitors
25
What contraceptives are weight neutral?
Ortho Evra
Ortho Tri Cyclen
26
What antimigraine meds are weight neutral?
Nortriptyline
Topiramate
27
Which patients do we recommend bariatric surgery?
BMI \>35 with comorbid conditions OR BMI \> 40
28
For which patients is medication recommended to treat obesity?
BMI \>27.5 with comorbid conditions OR \>30
29
What are tips for successful weight loss?
Exercise, modify caloric intake
(Watch less TV, weigh yourself, eat breakfast)
30
What is a very low calorie diet defined as?
400-800 calories per day
31
What is a low calorie die defined as?
800-1500 calories per day
32
What is a balanced diet defined as?
\>1500 calories per day
33
What defines starvation diet?
0-400 calories per day
34
Does exercise cause weight loss?
Not in and of itself, unless you exercise 2.5+ hours per day
Energy expenditure of physical activity is only 20%, remember
35
What is orlistat?
Lipase inhibitor that prevents lipid digestion - causes steatorrhea
Obesity treatment
36
What are phentermine and diethylpropion used for in nutrition?
For obesity/weight loss
37
Are bariatric surgeries effective?
YES, very much so
And weight loss is maintained
38
What factors regulate GI motility?
CNS and ANS
ANS - Sympathetic, Parasympathetic, and Enteric NS
39
What ANS factors regulate GI motility?
Sympathetic - fight or flight - inhibit digestion
Parasympathetic - stimulate digestion via vagus nerve
Enteric Nervous System
40
What are voluntary responses iof the Brain-Gut axis (CNS)?
Control of swallowing
Contraction of the external anal sphincter
(skeletal muscle based)
41
What are involuntary muscle responses of the Brain-Gut axis (CNS)?
Emotion
Stress associations
Conditioned responses
(Smooth muscle mediated)
42
What are parasympathetic inputs to the GI?
Vagus up until distal 2/3 of colon (via ACh)
Sacral plexus for the last 1/3 of colon
43
What are sympathetic inputs ot the GI?
Superior cervical gangion
Thoracolumbar - Prevertebral ganglion
44
Where is Myenteric Plexus (Auerbach's) located?
Between longitudinal and circular muscle layers
45
Where is the Mucosal (Meissner's) Plexus located?
Between circular muscle layer and submucosa
46
Where is skeletal muscle located in the GI?
Pharynx
Upper esophageal sphincter
Upper 1/3 of esophageal body
External anal sphincter
47
Where is smooth muscle located in the GI tract?
Lower 2/3 of esophagus
Stomach
Small and large intestine
Internal Anal sphincter
48
What can go wrong in the GI system that can cause defects in motility?
Muscle
Nerve
Brain-gut axis
Structural vs functional issues
49
What are symptoms of problems with GI motility?
Nausea/Vomiting
Pain
Early satiety
Diarrhea
Constipation
Diarrhea alternating with constipation
Gas
50
What is the origin of the motility of the GI tract?
Electrical activity - Slow waves with spike activity
Slow waves provide constant background rhythm that is propagated down GI tract and control phasic contractions (each organ has characteristic slow wave frequency)
Spike activity occurs when threshold for action potential is reached, causing rapid depolarization that results in contractions
51
What are the pacemaker cells of the gut?
Interstitial cells of Cajal (ICC)
52
What are GISTs?
GI stromal tumors - tumors of the interstitial cells of Cajal - may lead ot GI motility issues
53
What are interstitial cells of Cajal (ICC) cells?
Pacemakers of the gut
54
Which part of the gut has the highest frequency of electircal activity?
Small intestine - more going on
55
Which segmetn of the GI tract has the slowest frequency electrical activity?
Stomach
56
What are the two major type of contractions in the small intestine?
Peristalsis - slow proximal to distal movement
Segmentation - major contractile acitivity - contraction of circular smooth muscle
57
What is segmentation?
Major contractile activity of the small intestine - circular smooth muscle contraction
58
What is the major contractile activity of the small intestine?
Segmentation
59
What controls Peristalsis?
5HT, Substance P, Nitric oxide, ACh
Controled by a switch or gate that commands neurons
60
How do the motor functions of the stomach differ between fundus/body and antrum?
Fundus/body is more receptive relaxation and acts as a reservoir
The antrum mixes and grinds food which is vagally mediated
61
What area of the stomach regulates the emptying of liquids?
Fundus and body
62
What area of the stomach regulates the emptying of solids?
Antrum
63
What are some causes of gastroparesis (slow gastric emptying)?
Diabetes
Thyroid disease
Connective tissue disorders
Pregnancy
64
What is a motility issue commonly seen in diabetes?
Gastroparesis (slow gastric emptying)
Exacerbated by elevated blood sugar
65
What causes accelerated gastric emptying?
Dumping syndrome
66
How does the small bowel motility change between fed and fasting states?
Fed - segmental, promotes mixing and absorption of food
Fasting - cyclic, keeps intestine swept clean of bacteria and other tissue - Migrating Motor Complex (MMC)
67
What is the migrating motor complex?
"Housekeeper of the GI tract)
Turned off during a meal - so that segmentation can occur
68
What are neurologic factors that can cause small bowel dysmotility?
Parkinson's
Post-viral
69
What are smooth muscle issues that can cause small bowel dysmotility?
Collagen vascular disease
Systemic sclerosis
Polymyositis
Amyloidosis
70
What are endocrine issues that can cause small bowel dysmotility?
Diabetes
Hypothyroidism
71
What are drugs that can cause small bowel dysmotility?
Opiates
Anticholinergics
72
What are myenteric plexus disorders that can cause small bowel dysmotility?
Visceral neuropathies
73
What is chronic intestinal pseudoobstruction (CIIP)?
Diffuse problem that can affect the small bowel in its entirety
Myopathy (familial, collagen vascular, amyloid) or enteric neuropathy (Hirschsprungs, Chagas, Paraneoplastic, Idiopathic)
Abdominal pain, N/V, anorexia, diarrhea, malnutrition, weight loss
74
What are the two patterns of motor activity of the colon?
HAPC (High amplitude propagating contraction)
LAPC (Low amplitude propagating contraction)
75
What are LAPCs?
Low amplitude propagating contractions
Amplitude \< 50 mmHg
Occur frequently to transport fluid contents of the large intestine
Associated with distension and flatus
76
What are HAPCs?
High amplitude propagating contractions
Amplitude \> 100 mmHg
Occur infrequently and function to move masses
Strongly associated with defecation
77
When can you see constipation/
Normal
Irritable Bowel Syndrome
Metabolic
Colonic inertia
Pelvic floor dysfunction (megarectum, structural/funcitonal, dyssynergia/anismus)
78
What is functional constipation?
Chronic constipation that includes at least 2 of :
Straining for \>25% of defecations
Lumpy/hard stools
Incomplete evacuation
Anorectal obstruction/blockage
Manual maneuvers needed
\< 3 defecations per week
Rarely include loos stools
79
What is Ogilvie's Syndrome?
Acute pseudoobstruction
Non-obstructive colonic dilatation due to drugs, post-op state, immobility, electrolyte imbalances
Treat the underlying condition, and perhaps decompress the colon if necessary
Neostigmine can be used to stimulate parasympathetics
80
What is irritable bowel syndrome?
Recurrent abdominal **pain** or discomfort at least 3 days/month associated with 2+ of:
Improvement with defecation
Change in stool frequency
Change in stool appearance/form
81
What is the difference between irritable bowel syndrome and functional constipation?
**Pain** = IBS
82
What causes the pain in Irritable bowel syndrome?
Visceral hyperalgesia
Increased motor reactivity, altered visceral sensation, involves small and large intestine, CNS-ENS dysregulation
83
What is the pathophysiology of irritable bowel syndrome?
Hyperalgesia of the bowels - increased sensitivity to pain
84
How do enterochromaffin cells help motility?
Stimulate interneurons (increased transit) and epithelium cells (secretion)
85
How is serotonin involved in dysmotility?
5-HT is important in motility and in secretions
86
How do you approach irritable bowel syndrome patients?
Reassurance and education
Dietary and behavior modification
Pharm = laxatives, antidiarrheals, antidepressants, 5-HT receptor agents
Psychological treatments
87
What is defecation?
Propagation of intraluminal contents to rectum followed by sensation of fullness
Internal anal sphincter relaxation and external anal sphincter contraction
Anorectal angle straightens, with straining, puborectalis muscle and EAS relax, pelvic floor descends and anorectal angle straightens further
After elimination, tonic activity returns
88
During defacation does the internal anal sphincter relax or contract? What about external anal sphincter?
Internal = relax
External = contract
89
What muscles maintain continence?
Internal anal sphincter (70%) - continuation of colon
External anal sphincter (30%)
Levator ani muscles
Rectal curvature and transverse rectal folds
90
Does the internal anal sphincter contain smooth or striated muscle?
Smooth
91
Does the external anal sphincter contain smooth or striated muscle?
Both
92
What is fecal incontinence?
Release of rectal contents against one's wishes (7.9% of population)
More common in women, elderly and institutionalized individuals
Not often volunteered
93
What are things that can factor into incontinence?
Functional abnormalities
Structural abnormalities
Other
94
How do you treat fecal incontinence?
Anti-diarrheals
Bowel training/biofeedback
Surgery (last resort)
Depends on cause
95
How do you evaluate motility disorders?
Contrast radiography
Scintigraphy
Electrogastropathy
Hydrogen Breath Test
Sitz Marker Studies
Manometry
Defecography
MR Defecography
96
How does visceral abdominal pain present?
Vague, poorly localized
Dull, aching, burning, gnawing
97
What type of pain is vague, poorly localized and can be identified as dull, aching, burning, gnawing?
Visceral
98
How does somatic or parietal pain present?
Pinpoint, well localized
Sharp or stabbing pain
99
What type of pain presents as pinpoint, well localized, with sharp or stabbing quality?
Somatic or parietal pain
100
Why is visceral pain dull and poorly localized?
Visceral afferent nerves are few in number and are bilaterally represented
They diverge over several (up to 8) spinal segments when they enter the spine
They converge in dorsal roots with afferents from different locations
101
What can stimulate visceral nerves?
Distention
Traction
Pressure
Smooth muscle contraction
Ischemia
102
What can lower the pain threshold in visceral and somatic afferents?
Local ischemia and inflammation
103
What is the effect of local ischemia and inflammation on the pain threshold in visceral and somatic afferents?
Lowers the threshold
104
Why is somatic pain well-localized and sharp in nature?
There are numerous afferents that are unilaterally represented
They are highly segmental (travel at somatic levels)
Present in abdomina lwall, diaphragm, mesenteric roots, and superior hepatic ligaments
105
What can epigastric pain be indicative of?
Somtach, duodenum, gallbladder, pancreas
106
What does right upper quadrant pain indicate?
Duodenum, gallbladder, pancreas, right kidney
107
What does left upper quadrant pain indicate?
Pancreas, left kidney, stomach
108
What does central abdominal pain indicate?
Pancreas, small bowel, appendix
109
What does lower right quadrant pain indicate?
Right colon, appendix, terminal ileum, right ureter
110
What does left lower quadrant pain indicate?
Left colon, ureter
111
What does lower abdominal pain indicate?
Colon, bladder, uterus
112
What does left shoulder pain indicate?
Central left diaphragm
113
What does right back shoulder pain indicate?
Liver, hepatic ligaments, central right diaphragm
114
What does middle back pain indicate?
Pancreas
115
What does mid/upper right back pain indicate?
Gall bladder
116
What does lower back pain indicate?
rectal pain
117
What is the visceral pain reflex phenomena?
Visceral pain by peripheral and autonomic nerves at the level of entry into the spinal cord that leads to:
Decreased bowel motility (reflex sympathetic ileus)
Reflex contraction of skeletal muscle and adjacent spinal segments (involuntary guarding)
Changes in local blood flow and sweating
Lowering of cutaneous nerve endings' pain threshould (cutaneous hyperesthesia)
118
What does appendicitis feel like at first?
Periumbilical diffuse pain
Can also feel generally sick, or not well (poorly described)
119
What is the pathophysiological cause of appendicitis?
Luminal obstruction (fecalith may be present) causes increased intraluminal pressure that causes increased wall tension and distension (visceral pain and local inflammatory response)
Venous pressure is then exceeded, which causes a vicious cycle of increasing pressure -\> distension -\> ...
This leads to ulceration of mucosa, bacterial translocation, peritoneal inflammation with ischemia, followed by gangrene and/or perforation
120
What is the most common site of diverticulosis?
Colon - not small bowel
121
What are causes of diverticular disease?
Low fiber "western" diet
"western" sedentary lifestyle
Leads to slow colonic transit and increased intraluminal pressures
This combination leads to hard, dry stools that requires increased work to propel feces
122
What happens to the colon in the pathophysiology of diverticular disease?
Muscular hypertrophy (chicken or egg?)
Segmentation of the sigmoid colon
Increased intraluminal pressure that is transmitted to the colonic wall
Resulting in herniation of the mucosa and submucosa at points of weakness (pseudo-diverticula)
123
Where are weak points in the colon that are susceptible to diverticula?
The places where the blood vessel invades the muscularis
124
What are sequellae of diverticular disease?
Similar to appendicitis (can engorge, swell, perforate, infect, etc)
Can ulcerate, bleed, etc.
125
What are symptoms of diverticular disease?
Majority are asymptomatic, but:
Crampy abdominal pain
Left lower quadrant pain (commonly in sigmoid colon)
Constipation
126
What area of the colon is diverticulosis more common?
Sigmoid colon
127
What are some symptoms of diverticular disease?
Pain, fever, leukocytosis
128
What is needed for a diagnosis of diverticulosis?
History, physical, CT scan
129
What are treatment options for diverticulosis (diverticular disease)?
Antibiotics
Increased fiber in diet
Avoid constipation
Surgery for multiple recurrences or fistulae
130
What is diverticular bleeding?
Erosion of arteriole at the mouth of the diverticulum
Painless, but typically presents with brisk rectal bleeding (not occult)
131
How do you diagnose diverticular bleeding?
Colonoscopy or CT/MRI Angiography (may be hard to localize which diverticulum is bleeding)
132
How do you treat diverticular bleedign?
Most will stop on their own (caution against aspirin or anti-platelet agents)
Colonoscopic cauterization
Angiographic embolization
Surgery if refractory
133
What is the goal of the history and physical exam in GI bleeds?
To distinguish upper vs lower bleeds
134
What does hematemesis indicate?
Upper GI bleed
135
What does coffee-ground emesis indicate?
Upper GI bleed
136
What does melena indicate?
Upper more often than lower GI bleed
137
What is hematochezia indicative of?
Lower or massive upper GI bleed
138
What are vital sign abnormalities in GI bleed patients?
Hypotension, tachycardia - hypovolemia from blood loss
139
What do you see on CBC in acute bleeds?
May have delay in hematocrit drop (since you lose whole blood
INitial hematocrit may not reflect degree of blood loss
140
Why do you get elevated BUN in GI bleeds?
From hypovolemia and absorbed blood protein
141
What does an elevated BUN indicate?
Upper GI bleed - absorbed blood protein
142
Why is NG tube lavage not reliable?
False negatives - tube coiled in stomach, but bleed is from duodenum
False positives - blood from trauma of passing the tube
143
What are some hints for the source of an Upper GI Bleed?
Aspirin or NSAID use
Hx of peptic ulcer disease
Presence of liver disease (varices, gastropathy)
Preceding retching (Mallory-Weiss tear)
GERD symptoms (esophagitis)
Prior Aortic aneurysm surgery (aorto-enteric fistula)
Weight loss (neoplasm)
144
What is hematochezia?
Red/maroon blood, sometimes with clots, usually associated with frequen BM or passage of pure blood
145
What is overt bleedign?
Actually see blood in stool
146
What is occult bleedign?
Microscopic blood in stool over weeks to months produces anemia and iron deficiency
147
What anatomical structure differentiates upper from lower GI bleed?
Upper - proximal to ligament of Trietz
Lower - Ileocolonic
148
Why do you perform endoscopy for GI bleeds?
Locate the bleed
Endoscopially treat the bleed
Prognostically evaluate patient
149
What is the most commoon source of upper GI bleeds?
Peptic ulcer disease (gastric or duodenal)
Majority due to H pylori and/or NSAIDs/aspirin
150
How many GI bleeds do not spontaneously stop?
20%
151
What are some danger signs of upper GI bleeds?
Shock
Number of units of packed RBCs transfused
age \> 60
Comorbidities
Melena and hematochezia (big vessel)
Active bleeding or large ulcer seen on EGD
152
How do you treat GI bleeds due to peptic ulcer disease?
Fluid resuscitation, IV PPI, urgent/emergent endoscopy
Surgery is reserved for failure of medical therapy
Stop NSAIDs, look for H. Pylori
153
What is this?
Erosive Gastritis
154
What is this?
Hemorrhagic Gastritis
155
What type of GI bleed do neoplasias typically cause?
Chronic bleeds - less comonly present with melena or hematemesis
Therapy is surgical, Chemo/RT
156
What is a Mallory-Weiss tear?
Retching leads to mucosal tear at E-G junction.
Usually self-limited
157
Why do bleeding varices carry high mortality rate?
Lots of blood, also, you have the underlying causes that led to them too
158
What is this? 
Mallory-Weiss Tear
159
What is this?
Esophageal Varices
160
What is a Dieulafoy lesion?
Large caliber artery, usually present with significant bleeding that can start and stop
161
What is GAVE?
Gastric Antral Vascular Ectasia (Watermelon stomach)
Dilated mucosal vessals, more commonly seen in renal patients, elderly
162
What is Aorto-Enteric fistula?
Massive bleedign in patient with prior aortic graft (aneurysm, etc) that erodes into duodenum
Can have Herald bleed
163
What is a herald bleed?
Initial significant bleed that stops, only to recur massively
164
What are Cameron Lesions?
Erosions or ulcerations that occur within a hiatal hernia
Can lead to iron deficiency anemia
Rare cause of hematemasis or melena
165
What is this? 
Watermelon stomach (GAVE)
166
What are endoscopic therapies for GI bleeds?
Injection therapy (epinephrine, sclerosing agents)
Hemostatic therapy (cauterizing shut the bleed)
Band ligation
Clips
167
How does Lower GI bleed present?
Usually with hematochezia, frequently stops spontaneously or bleeds intermittently
168
What are most common causes of lower GI bleeds?
Chronic:
Hemorrhoid - painless blood on tissue or in bowl
Fissure - tearing/ripping as BM passes anal canal
Colitis - urgency, tenesmus, diarrhea, mucus
Polyp - blood mixed with stool
Acute:
Diverticulosis
Arteriovenous malformations (AVMs)
169
Are hemorrhoids or anal fissures more painful?
Anal fissures - hemorrhoids are typically painless
170
How do you diagnose anal fissure?
Physical exam - spread buttocks, valsalva makes dentate line visible
171
What is the first line diagnostic evaluation of lower GI bleeds?
Colonoscopy
172
How do nuclear scans work for diagnosing lower GI bleeds?
Technetium labeled RBC scan
20 mL of blood drawn, tagged with Tc-99m, reinjected and scanned at intervals
Can be repeated within 24 hours if the patient rebleeds
Can detect bleeding at low levels
173
What is the difference between angiography and nuclear scans?
Angiography requires greater blood volume bleeds to be seen
174
What is a benefit of angiography?
Can allow for intervention
175
What are drawbacks of angiography?
Require high bleeds
Has up to 10% rate of complications
176
What is "Obscure" GI bleedign?
Not upper or lower endoscopically visualized
Typically Small Intestinal:
Vascular (AVM)
Neoplastic
Inflammatory
Meckel's Diverticulum
Biliary
Pancreatic
177
What is significant about Meckel's diverticulum wrt bleeds?
Most common cause of bleeds in patients \< 3 years old and in small bowel bleed cases in men \< 30 years old
178
What is a Meckel's Scan?
Tc-99m injected, accumulates in gastric mucosa
Can be considered early in workup of obscure GI bleed in younge otherwise healthy patients
179
How do you visualize the small bowel?
Push enteroscopy - can't visualize most of it
Intra-operative endoscopy - high rate of complications
Capsule endoscopy - camera in a pill
Double-balloon method
180
What are TLESRs?
Transient lower esophageal sphincter relaxations - major cause of GERD
181
What is the effect of cholinergic/anticholinergic drugs on the LES pressure?
Cholinergics increase LESp, Anti-cholinergics decrease LESp
182
What is the effect of progesterone on the LES pressure?
Decreases LESp
Significant in pregnancy
183
What is the role of gastrin on parietal cell acid secretion?
184
What is the role of histmaine on parietal cell acid secretion?
185
What is the role of acetylcholine on parietal cell acid secretion?
186
What is the role of somatostatin on parietal cell acid secretion?
Feedback inhibition
187
What is the primary acid producing cell in the stomach?
Parietal cell
188
What is the basal stomach pH?
2-Jan
189
What is post-prandial stomach pH?
4-5 (around 1 hour after eating)
190
What are defense mechanisms that allow the stomach to not eat itself?
Tight junctions b/w gastric epithelial cells
Mucin layer overlying cells
Bicarb ions secreted into mucin layer
Prostaglandins (stimulate mucus production, epithelial cell repair, bicarb, and mucosal blood flow
191
What are drugs that control gastric acidity?
Antacids
Cytoprotectants
H2 receptor antagonists
PPIs
192
How do antacids work?
Local neutralization of acid
Aluminum hydroxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate
193
What is aluminum hydroxide?
Antacid
194
What is magnesium hydroxide?
antacid
195
What is calcium carbonate?
antacid
196
What is sodium bicarbonate?
Antacid
197
What are the cytoprotectants?
Sucralfate
Misoprostol
Bismuth compounds
198
How do cytoprotectants work?
Bind to base of ulcer
Promote mucin and bicarbonate production
Has some antibacterial effects
May produce melena - tell patients its ok
199
What is misoprostol?
Prostaglandin E analog
Stimulates secretion of mucin and bicarb
Increases mucosal blood flow
Can have diarrhea nad abdominal cramps due to smooth muscle contraction; increased uterine contraction (contraindic. in pregnancy); used in combination for medical termination with MTX or mifepristone
200
What is a non-indicated use of misoprostol?
Abortion, when used in combination with methotrexate or mifepristone
201
How do H2 receptor antagonists work?
Competes with histmaine for receptors on parietal cells
(Cimetidine, Ranitidine, Famotidine, Nizatidine)
202
What is cimetidine?
H2 receptor antagonist
203
What is ranitidine?
H2 receptor antagonist
204
What is famotidine?
H2 receptor antagonist
205
What is Nizatidine?
H2 receptor antagonist
206
When are H2 receptor antagonists indicated?
Gastric and duodenal ulcers
Uncomplicated GERD
Stress ulcer prophylaxis
207
What are drug interactions of H2 receptor antagonists?
Interfere with absorption of drugs that require acidic environment
Cimetidine inhibits CYP450
208
What is omeprazole?
PPI
209
What is lansoprazole?
PPI
210
What is rabeprazole?
PPI
211
What is pantoprazole?
PPI
212
What is esomeprazole?
PPI
213
What are drugs that end in -prazole?
PPIs
214
How do PPIs work?
Pro-drug that requires protonation in acidic environment
Must be enteric coated since parent compound is unstable
Irreversibly binds to and inactivates H/K ATPase in parietal cell (doesn't "kill" parietal cell)
IF release not affected
215
Do PPIs affect Intrinsic Factor release?
NO
216
What conditions are PPIs used for?
Gastric and Duodenal ulcers
GERD
Zollinger-Ellison Syndrome
IV for upepr GI bleeding
217
What are adverse effects of PPIs?
Hypergastrinemia - ECL hyperplasia - rare risk of gastric carcinoid
Increase C diff and other infections
Interaction with clopidogrel via CYP450
Increased risk of osteopnia and osteoporosis
218
What is Celecoxib used for in GI ?
COX1 is predominant in gastric cells leading to produciton of PGs that enhacne mucous production
COX 2 is important in mediating systemic inflammation
COX2 is less likely to cause gastro-duodenal injury
Celecoxib is COX 2 selective inhibitor
219
What is the location of the panreas?
Retroperitoneal, 4-5th lumbar spine
220
Wqhat ist he arterial supply of the pancreas?
Gastroduodenal
SMA
Splenic artery
221
What is the venous drainage of the pancreas?
Portal Vein
Splenic Vein
222
What are the nerves that innervagte the pancrease?
Vagal (stimulatory)
Sympathetic (inhibitory)
223
How does the pancreas devlelop?
5 weeks - two buds
6-7 weeks, twisting
8 weeks - joining of buds
224
Where does the main pancreatic duct drain?
Major papilla
225
Where does the accessory pancreatic duct drain?
minor papilla
226
What structures join at the major papilla?
Bile duct, pancreatic duct
Each has sphincter. Sphincter of Oddi does both
Papilla of Vater is another name for this area
227
What percentage of the function of the pancreas is endocrine vs exocrine?
Endocrine 2%
Exocrine = rest
228
How is pancreatic bicarb secretion regulated?
Acid to S cells in duodenum release secretin which activates pancreatic duct cells to produce bicarb
229
How does CCK regulate pancreatic enzyme release?
Amino acids and peptides activate endocrien cells of duodenum which release CCK
These act on the acinar cells of pancreas, which release enzymes
230
What pancreatic cells does CCK act on?
Acinar cells
231
What pancreatic cells does secretin act on?
Ductal cells
232
What is the major enzyme output of the pancreas
Proteases
To lesser degree lipases, glycosidases, nucleases
233
How do pancreatic zymogens get activated?
Enterokinases activate trypsinogen to trypsin, which can in turn catalyze reactions from other zymogens to active enzymes
Enterokinase only in duodenal brush border
234
What are mechanisms by which the pancreas protects itself from its own degradation?
Synthesis of enzymes as zymogens
Trypsin inhibitor packaged into zymogen granule
Segregation of enzymes in membrane-boudn compartments
Enterokinase restricted to small intestine
235
What are mechanisms of acute pancreatitis?
Insult causes ischemia whcih causes inflammation, zymogen activation, systemic inflammation, death. etc..
236
What is teh pathologic activation cascade?
When you get trypsinogens converted to trypsin not in the duodenum... This causes cascade of zymogen activation that can be disastrous
237
What causes pancreatitis?
Gallstones (45%) - older patients, more common in females
Alcohol (35%) - younger patients, more common in men
238
What are etiologies of acute pancreatitis?
Drugs
Trauma
Metabolic
Obstruction (stones, etc.)
Pregnancy
Infection
ESRD
Scorpion bite
Idiopathic
Miscellaneous (autoimmune, other)
239
How can gallstones cause acute pancreatitis?
Common bile duct stone that obstructs both ducts
240
How can alcohol cause acute pancreatitis?
Intracellular accumulation of pancreatic enzymes
Increased permeability of ductules
Increased tendency to form protein plugs causing obstruction
241
What is a condition where you have a mismatch between pancreatic duct and the papilla that is supposed to drain it?
Divisum - ducts are not fused; man pancreatic duct drains through minor papilla
Can cause pancreatitis
242
What is ERCP?
Endoscopic Retrograde Cholangio-pancreatography
Scope that gives you view of papilla. Can inject dye and see how it drains
243
What are clinical features of acute pancreatitis?
Pain is ALWAYS present; may radiate to back
N/V common, fever
Peritoneal signs are generally absent (not really guarding)
Ileus may arise due to extenison into small intestinal and colonic mesentery
244
What are lab values that you can see in pancreatitis?
Leukocytosis
Hyperamylasemia
Hyperlipasemia
245
What are things on the differential for pancreatitis?
Choledocholithiasis
Perforated ulcer
Mesenteric ischemia
Intestinal obstruction
Ectopic pregnancy
246
What forms of pancreatitis are more likely to cause organ failure?
Necrotizing pancreatitis (54%)
247
What is systemic inflammatory response syndrome?
SIRS
2+ of:
Pulse \> 90
RR \> 20 or PCO2 \<32 mmHg
Rectal Temp \<36 or \>38
WBC \< 4000 or \>12000
248
How do you diagnose acute pancreatitis?
Clinical picture + lab values +/- imaging
Increased amylase and lipase 3x normal
Lipase is more specific
Check renal clearnace
249
How do you predict who does well vs poorly in pancreatitis?
Ranson's criteria
APACHE II score
Serum hematocrit
and others
Gold standard = Ranson's
250
What imaging modalities are useful for pancreatitis?
CT w/ contrast (edema and stranding)
Ultrasound for detection of stones
MRCP - MRI equivalent of ERCP - non-invasive
ERCP - invasive - sedated
251
What do you see here?
Gallstone pancreatitis
252
What can you look for to ensure gallstone pancreatitis diagnosis?
Transient elevation in liver chemistries
Ultrasound
Bile aspiration analysis - check for crystals
MRCP
ERCP
253
How do you treat interstitial pancreatitis?
Resuscitate fluids (lots of fluids)
Rest the pancreas (NPO)
Pain control
Maintain nutrition
Address underlying cause (stones, drinking, offending agent if drug)
254
What is short-term treatment for stone disease as root of pancreatitis?
ERCP
255
What is a long-term treatment for stone releated pancreatitis?
Cholecystectomy
ERCP is for short term
256
What is a concern with necrotizing pancreatitis?
Organ failure
Infection - do gram stain, etc
257
What are local complications of pancreatitis?
Pseudocyst - no epithelial lining so not a true cyst; mostly asymptomatic, causes early satiety if it compresses stomach/duodenum. Drain it by endoscopy
Abscess
HEmorrhage
258
How do you identify/treat pseudocyst as a result of pancreatitis?
\>4 weeks after actue pancreatitis
Mostly asymptomatic
But can have early satiety if it infringes on duodenum or stomach
Drain it by endoscopy interventional radiology or surgery
259
What are systemic complications of acute pancreatitis?
ARDS - Acute Respiratory Distress Syndrome
DIC
Renal Failure (part of multi-organ failure)
Treat with broad spectrum Abx
Intubate
Supportive care
260
What is chronic pancreatitis?
Chronic inflammation with irreversible morphologic changes that can lead to lsos of exocrine and endocrine function
261
What is the #1 cause of chronic pancreatitis?
Alcohol
262
What are causes of chronic pancreatitis?
#1 - alcohol
Otehrs: Tropical; pancreas divisum; autoimmuen; neoplastic; etc.
263
What is the abnormal secretion theory for the pathogenesis of alcoholic pancreatitis?
Protein plugs cause decreased lithostatine (pancreatic stone protein), leads to progressive blockage of ducts
264
What ist he necrosis-fibrosis theory of alcoholic pancreatitis pathogenesis?
Acute attacks of pancreatitis lead to necrosis -fibrosis of the duts results with obstruction
265
How do you diagnose chronic pnacreatitis?
Severe pain radiating to back - daily pain with exacerbations or painfree intervals between exacerbations
Steatorrhea and weight loss and FLAT PLATE X-RAY to check for calcifications
MRCP/ERCP and ultrasound can help
Secretin stimulation test - rarely done
266
What do you see here?
Chronic pancreatitis
Calcifications
267
How do you treat pain in chronic pancreatitis?
Stop alcohol!
Analgesics (non narcotics or narcotics)
Pancreatic enzymes to reduce CCK secretion (non-enteric coated - give w/ PPI)
Invasive procedures (nerve block, endoscopic decompression, surgical drainage)
268
How do you treat malabsorption of chronic pancreatitis?
Pancreatic enzyme
Decrease dietary fat
Substitute medium chain triglycerides
269
What are complications of chronic pancreatitis?
Pseuydocyst
Diabetes
Steatorrhea
Obstruciton of bile duct
Duodenal obstruction
Pancreatic ascites or adenocarcinoma
270
What is the most common pancreatic neoplasm?
Adenocarcinoma
271
Who gets pancreatic neoplasms?
Men in 60s, smokers
272
Where in the pancreas do neoplasmsm typically present?
2/3 of head of gland
1/3 body/tail of it
273
What are clinical features of pancreatic neoplasms?
Painless jaundice
Nonspecific symptoms (abdominal pain, anorexia, N/V, depression, new onset diabetes)
Phys exam - jaudnice - Courvoisier's sign (palpable gallbladder)
274
How do you diagnose pancreatic carcinoma?
CT/MRI
275
How do you treat pancreatic carcinoma?
Surgery, chemotherapy
ERCP with stent to palliate pruritus
276
What are nonpancreatic carcinoma pancreatic neoplasms?
Pancreatic Neuroendocrine tumors (PNETs)
Functioning - gastrinoma, insulinoma, glucagonoma, VIPoma
Diagnosis with EUS, octreotide scan
Treat with octreotide, surgical resection, chemoembolization
277
What are unique features of the biliary tract?
Tri-section of hepatic, pancreatic, and intestinal tracts
Repercussions of all three systems
Biliary tract - except for gallbladder, it is essential for life
278
What are components of bile?
Mostly water
Bile salts, phospholipids, cholesterol and other components make up the rest
279
Where is bile made?
Liver
280
What does bile do?
Secretory - carries stuff body needs to function - micelle-forming bile acids, phospholipids, IgA
Excretory - produces stuff body gets rid of - cholesterol, bile pigments, trance minerals, plant sterols, etc etc
281
What factors affect bile flow?
Liver function
Concentration of bile acids in bile
Other ATP dependent pumps
The gall-bladder (can sequester bile in fasting state)
Biliary tree patency, sphincters, motility
Small intestinal patency and motility
282
What is the effect of bile acids on bile flow?
Induces further flow of bile - greater concentraiton of bile acids, greater flow of bile
283
What is the role of bile acids in the liver?
Induces bile flow (bile acid-dependent role)
Transports cholesterol and phospholipids - micelles
284
What is the role of Bile acids in the intestines?
Fat digestion
Catharsis - move bowels
285
What is the chemical feature of bile salts that is important in its funciton?
Ampiphilic - works as detergent (polar and non-polar portions)
286
What is an important precursor in the formation of bile salts?
Cholesterol
287
What are the primary bile acids?
Chenodeoxycholic acid and Cholic acid
288
What are the secondary bile acids?
Deoxycholic
Lithocholic
289
What is the enterohepatic circulation of bile salts?
Secreted into bowels, reabsorbed
Only \<5% is made again, so need to absorb 95% of it
290
Where are bile salts absorbed?
Predominantly in ileum - some in jejunum and colon
291
What is the function of hepatocyte canaliculus in biliary tract?
bile formation
292
What is the funciton of ductules and ducts in the biliary tract?
Modificaiton of bile (absorption and secretion
293
What is the fucntion of the gallbladder in the biliary tract?
Concentration
Storage
Controlled delivery (CCK)
294
What is the funciton of the sphincter of Oddi in the bililary tract?
Regulated delivery of bile to duodenum
Prevention of reflux
295
What is the role of CCK in biliary tract?
Causes gallbladder to contract
296
What is cholelithiasis?
Gallstones - obstruciton of gall bladder
297
What is cholecystitis?
Gall bladder infection
298
What are abnormalities of bile acid metabolism?
Defective bile acid synthesis
Abnormalities of delivery to intestine
Interruption of enterohepatic circulation
Bile acid malabsorption
Bacterial overgrowth syndrome
Cholestasis - stand still in tree
Liver disease
299
What is cholestasis?
Decerased bile flow
300
What can cause cholestasis?
Cholestatic drugs, pregnancy and other processes that affect canaliculus, biliary ductules, that can be detected by lab tests and liver biopsy
Congenital biliary atresia - affects intrahepatic bile ducts that can be detected by imaging, ERCP, PTC
Common duct stone, cancer of pancreas or bile duct - that affects extrahepatic bile ducts, can be diagnosed by imaging, ultrasound, ERCP, PTC
301
What are consequences of cholestasis?
Hepatic retention of biliary solutes and intestinal deficiency of digestive detergents (bile acids)
Retain bile acids, bilirubin, cholesterol
Malabsorption of fats, vitamins, etc
302
What are causes of interruption of the enterohepatic circulation of bile acids?
External biliary fistula
Ileojejunal exclusion for obesity
Binding exchange resins
Small bowel disease
303
What is the effect of bile acids on GI organs?
Esophagus - damage, esophagitis
Stomach - damage, gastritis
Pancreas - pancreatitis
Colon
304
What is choledocholithiasis?
Stones in the bile ducts
305
What do we see here via laproscopy?
Gall stones (cholelithiasis)
306
What are two types of gall stones?
Cholesterol stones
Pigmented stones
307
What are mixed stones of the gall bladder?
Both cholesterol and pigment stones
308
What are cholesterol stones?
Crystals of cholesterol
309
What are pigment stones?
Precipitates - not crystals
310
What are pigmented gallstones?
Composed of bilirubin and/or calcium precipitates (not crystals)
Can form whenever there are high concentrations of unconjugated iblirubin in bile
Can arise in either gallbladder or bile ducts
Can be seen in liver disease, hemolysis, ifnected bile, prolonged starvation or total perenteral nutrition
311
What is the basis for pigmented gallstones?
High concentrations of unconjugated bilirubin in bile
312
Where do you find pigmetned gallsotnes?
Gallbladder and biliary ducts
313
What is the relationship between bile acidity and ability to form precipitates?
More acidic - more solubility - less acidic = more chance to form precipitates
314
What are cholesterol gallstones?
Most common form
Crystallization form lithogenic bile
Arises in gallbladder, NOT DUCTS
Female, fat, fertile, forty
315
Where do cholesterol gallstones form?
Gallbladder, NOT ducts
316
What type of gallstones can form in the bile ducts?
Pigmented; cholesterol only form in gallbladder (pigmented can too)
317
What are causes of cholesterol gallstone fomration/
Too much cholesterol or too few bile salts
318
What is the relationship between bile salt secretion rate (flow) and the risk of developing precipitates?
Slower teh secretory rate, the more likely you are to be in the supersaturated state (more likely to form precipitates)
319
What is the natural history of gallstones?
Typically asymptomatic - just because they exist, doesn't mean they are making the patient sick
320
How can gallstones make you sick?
Biliary colic - stone temporarily stuck in cystic duct
Acute cholecystitis - cystic duct obstruction and infectoin
Bile duct obstruction - cholestasis + cholangitis? (cholangitis - inflammation of biliary tree)
Acute pancreatitis
321
How do you get rid of gallstones?
Surgically - cholecystetomy = typically laprascopically
Non-surgical - lithotripsy (shock waves); gallstone dissolution (ursodeoxycholic acid)
322
Does cholecystectomy prevent patients from developing gallstones?
NO - cholecystectomy does not prevent bile from being supersaturated still (might have had crystals in gallbladder before removal that stayed behind)
323
what is the effect of ursodeoxycholic acid?
Secondary bile acid - decreases cholesterol secretion and cholesterol/phospholipid raito in bile
Main constituent of bear bile
ONly modestly effective and must be taken for a long time/indefinitely
Side effects include diarrhea, cost; but can be used to liquefy bile in other diseases
324
How do you diagnose gallstones?
Sonography (radar)
X-rays (plain or contrast)
Nuclear scan (HIDA scan)
Bile analysis (for cholesterol crystals)
Endscopy (ERCP)
325
What gallstones can be seen on x-ray without contrast?
Pigmented
326
What gallstones can be seen on xray with contrast?
cholesterol
327
What are diseases of the gallbladder?
Colic
Acute/chronic cholecystitis
Cancer
328
What are diseases of the biliary ducts?
Acute cholangitis
Sclerosing cholangitis
Biliary cirrhosis
Cancer
Dysmotility
329
Identify the Islets of Langerhancs, Acinar cells, and ductal epithelium
330
Which pancreatic cells are exocrine and which are endocrine?
Exocrine - acinar
Endocrine - Islet cells (α, β, etc )
331
What is the malformation of pancreas divisum?
Dorsal and Ventral pancreatic ducts fail to fuse together
Common bile duct and pancreatic duct do not drain together
Main duct goes to minor papilla
332
Where can you often find heterotopic/ectopic pancreas?
Stomach, duodenum
333
When do you typically find congenital/developmental anomalies of the pancreas?
Asypmtomatic, and can cause problems during surgery/endoscopy
Maybe secondarily involved by pancreas pathology
334
What are causes of acute pancreatitis?
Duct obstruction, acinar cell injury, defective intracellular transport
335
What do you see here?
Interstitial edema
Fat necrosis
**Acute interstitial pancreatitis**
336
What do you see here?
**Acute necrotizing pancreatitis**
337
What do you see here?
**Acute hemorrhagic pancreatitis**
338
Is acute panreatitis reversible?
YES
339
What is the main cause of acute pancreatitis in men?
Alcohol
340
What is the main cause of acute pancreatitis in females?
Gallstones
341
What are signs/symptoms of acute pancreatitis in acute pancreatitis?
Pain (radiating to the back), anorexia/nausea, increased serum amylase (later lipase)
Complications include infection, abscess, pseudocyst
342
What is the difference between acute and chronic pancreatitis?
Risk factors are the same
Acute - acinar cell injury followed by inflammation
Oxidative stress injury causes growth factor and pro-inflammatory molecule production
Production of stellate cells and resulting pancreatic fibrosis
343
What do you see here?
Chronic pancreatitis - duct dilation, fibrosis, and atrophy
344
Is chronic pancreatitis reversible?
NO - Irreversible destruction with fibrosis
345
What are histological findings of chronic pancreatitis?
Fibrosis
Atrophy of acini (reduced number/size)
Relative sparing of islet cells (initially)
Duct dilation with protein concretions
346
What are the most common cystic lesions of the pancreas?
Pancreatic pseudocyst
347
What are pancreatic pseudocysts?
Walled off hemorrhagic/necrotic debris
Lined by capsule/granulation tissue, NOT epithelium (diagnostic)
348
Why are pseudocysts not true cysts?
Lined by granulation tissue, notably NOT epithelium
349
What is the most common malignancy of the pancreas?
Pancreatic ductal adenocarcinoma
350
What are the most common gene mutations in pancreatic ductal adenocarcinoma?
KRAS
p16/CDKN2A
TP53
SMAD4/DPC4
351
What is a hereditary disease that associated with pancreatic ductal adenocarcinoma?
Hereditary pancreatitis
Peutz-Jeghers Syndrome
352
What do we see here?
Pancreatic ductal adenocarcinoma
353
What are physical exam findings of pancreatic ductal carcinoma?
Migratory thrombophlebitis (Trousseau sign)
Acute, painless jaundice and dilated gallbladder (Courvoisier sign/law)
Nontender firm, fixed, left supraclavicular lymph node (Virchow's or Troisier's node)
354
What is Trousseau sign?
Migratory thrombophlebitis
Seen in pancreatic ductal adenocarcinoma
355
What is Courvoisier sign/law?
Acute, painless jaundice and dilated gallbladder
Seen in pancreatic ductal adenocarcinoma
356
What is Virchow's node?
Nontender, firm, fixed, left supraclavicular lymph node
Seen in Pancreatic ductal adenocarcinoma and gastric adenocarcinoma
357
What do you see here?
Pancreatic neuroendocrine tumor
358
How are pancreatic neuroendocrine tumors classified?
Functional - insuloma, gastrinoma, glucagonoma, somatostatinoma, VIPoma
Nonfunctional - typically malignant
359
What is the most common functional pancreatic neuroendocrine tumor?
insuloma - causes hyperinsulinism (mild hypoglycemia)
360
What is the most common cause of acute cholecystitis?
Stones - Acute calculous cholecystitis
361
What do you find histologically in acute cholecystitis?
Lumen - fibrin, blood, neutrophils=empyema
Wall - edematous, thick, necrosis=gangrenous
Serosa - exudate, gas bacteria=emphysematous
362
What do you see histologically in chronic cholecystitis?
Fibrosis, Rokitansky-Aschoff sinuses
calcification (porcelain), atrophy (hydrops)
363
What do you see here?
Adenocarcinoma of the Gallbladder
364
What do you typically see with adenocarcinoma of the gallbladder?
Stones
More commonly seen in females
365
What are broad funcitons of the liver?
Synthesis of protein (albumin, clotting factors)
Substrate metabolism, storage (Carbs, lipids, vitamins, metals)
Metabolizes drugs, biotransformation
Excretes (bilirubin, bile acids, drugs)
Immune funciton
Growth Factor, hormone production
Hematopoiesis
366
What are broad types of liver disease?
Injury (acute/chronic: viral, toxic, metabolic)
Genetic (overload of metabolites, defective protein funciton or secretion)
Developmental (biliary atresia, cysts)
Neoplastic (benign tumors, adenmoas, pre-malignant and malignant tumors)
367
What liver dysfunction does a coagulopathy indicate?
Loss of clotting factor production
368
What liver function is impaired when you see jaundice, scleral icterus?
Bilirubin clearance
369
What liver function is dysfunctional when you see hypoglycemia?
Glucose mobilization
370
What liver function is dysfunctional when you see encephalopathy?
Metabolite clearance and drug detoxification
371
What liver function is dysfunctional when you see renal failure?
Blood flow regulation
372
What liver function is dysfunctional when you see sepsis and bacterial peritonitis?
Clearance of bacteria from portal blood
Immune function
373
What liver function is dysfunctional when you see anemia and reduced oncotic pressure leading to edema
Production of growth factors and albumin
374
What liver function is dysfunctional when you see feminization with gynecomastia in men?
Metabolism of hormones
375
What liver function is dysfunctional when you see portal HTN wiht varices and ascites?
Blood flow (can be obstructed due to increased scarring)
376
What cell type of the liver mediates the liver's immune system?
Kupffer cells - macrophages
377
What is unique about the blood supply of the liver?
Dual blood supply - portal vein and hepatic artery
378
What is unique about the endothelium of the liver?
Fenestrated
379
What organs drain into the liver?
Gut and spleen
380
What are features of the blood flow of the liver?
Low pressure
High capacitance
381
What is a unique feature of the organ important for transplantation?
Ability to regenerate
382
What are acute sources of liver injury?
Tylenol or toxins (alcohol)
Viral infection
Unknown (idiopathic)
May require transplant when severe, but if it resolves it can return to normal
383
What are chronic sources of liver injury?
Viral infection
Alcohol
Obesity-related
Autoimmune
Metabolic overload
Biliary obstruction
Can be progressive over decades but relatively asymptomatic
384
How does the liver respond to chronic injury?
Scarring (fibrosis) - acutely will typically regenerate, so it requires a chronic insult before it will scar
385
What is the endstage result of chronic liver disease?
Cirrhosis
386
What is seen on the right?
Cirrhosis
387
What do you see on the right?
Cirrhosis (normal on left)
388
What are complications of cirrhosis?
Hepatic encephalopathy
Ascities/Spontaneous Bacterial Peritonitis
Portal hypertension (varices)
Hepatorenal syndrome
389
What happens during cirrhotic liver blood flow?
Blood clogs up - see splenomegaly, varices, ascites, etc
390
What are histories of risk fators or exposures for liver disease?
Needle use, transfusions, prescribed or illicit drugs
391
What are signs/symptoms of liver disease?
Enlarged liver - acute injury or tumor
"Stigmata of chronic liver disease" - possible cirrhosis
392
What do elevated AST, ALT, bilirubin suggest?
Injury to **hepatocytes**
393
What do increased alkaline phosphatase γGT, bilirubin indicate?
Injury to bile ducts
394
What are diagnostic tests for liver disease?
Enzymes - AST, ALT, Alkaline Phosphatase, bilirubin
Function - albumin, prothrombin time, platelets
Systemic - CBC, renal function
Imaging
395
What do you see here?
Scleral icterus
Spider angioma
Glossitis
Liver disease possible
396
What do you see here?
Spider angioma
Seen in chronic liver disease and in pregnancy
397
What do you see here?
Palmar erythema
Can be sign of chronic liver disease
398
What do you see here?
Digital clubbing
Sign of chronic liver disease (not usually this severe)
399
What do you see here?
Signs of gynecomastia in a man
Can be a sign of liver disease
400
What do you see here?
Excoriations can indicate biliary obstuction (itchiness)
401
What do you see here?
Xanthelasma in cholestatic liver disease
Especially primary biliary cirrhosis
402
What do you see here?
Massive ascites
Large umbilical hernia
Collateral vessels on abdominal wall
Sign of chronic liver disease
403
How do you typically treat liver disease?
treat underlyign disease - antivirals, remove metabolites, reduce inflammation
Treat complications of liver disease (antibiotics, diuretics, reduce encephalopathy
Transplant
404
How many hepatits viruses are there?
5 - A-E
405
What is hepatitis?
Indicates biochemical hepatic dysfunction, not necessarily due to virus
406
What is acute viral hepatitis?
Can be any of 5 major viruses
Malaise, nausea, abdominal discomfort, jaundice are typical but not necessary
Recovery is usual
407
What is chronic hepatitis?
Persistence of hepatitis \> 6 months
Occurs with B, C, D
Risk of cirrhosis and hepatocellular carcinoma
Not in Hep. A
408
Which hepatitis viruses can cause chronic hepatitis?
B, C, D, maybe E
409
How do you diagnose viral hepatitis?
Serologically
Biopsy doesn't differentiate
ALT, and AST reflect hepatic necrosis
410
What is the incubation period of hepatitis A?
4 weeks
411
How do you diagnose hepatitis A?
IgM anti HAV during acute phase
IgG anti HAV persists indefinitely
412
How is hepatitis A transmitted?
Fecal-oral
Commonly affects children
413
How do you manage hepatitis A patients?
Self-limited
Follow older patients carefully because of risk of liver failure
No role for antiviral therapy - immune globulin post exposure
(there is vaccine)
414
How do you prevent hepatitis A?
Active immunization (inactivated/killed virus)
Recommended for travel to endemic areas, military, employees of daycare, people handling hep A specimens, people with chronic disease
415
What is the incubation period of hepatitis B?
60-90 days (2-3 months)
416
What is unique about the virus of hepatitis B virus?
Only DNA virus
417
What is a marker of hepatitis B replication?
HBV DNA
418
What is a marker of HBV replication **and infectivity**?
Hepatitis B E antigen
419
What is the first detectable virologic marker of Hep B infection?
HBsAg
Precedes rise in AST/ALT nad symptoms
Antibody appears after, and is detectable indefinitely
420
What is the only antibody detectable upon receiving HBV vaccination?
Anti-HBs (surface) antibody
Protective
421
422
How is Hepatitis B acquired?
Percutaneous (blood transfusion, needle stick)
Perinatal
Sexual
Most common cause of chronic hepatitis in Asia and Africa
(any age)
423
What are differences between childhood and adult hepatitis B infection?
Childhood = perinatal or preschool; infection is typically subclinical
Adult = sexual contact, IV drug use, exposure to blood; infection is typically sypmtomatic
424
Who are populations at risk of Hep B?
Hemodialysis
IV drug use
Spouses of acutely infected individuals
Promiscuous people (MSM)
Healthcare workers
Transfusion pts
Nursing home residents/staff
Prisoners
425
How many people progress to chronic hepatitis?
1-10% of patients - risk of developing cirrhosis, HCC
Fulminant (acute) liver failure is rare (0.1-0.5%)
426
What is the natural history of Hepatitis B?
427
What are forms of prophylaxis for Hepatitis B?
Active: plasma or recombinant vaccines
Passive: Hepatitis B immune globulin (HBIG) - not proven
428
What are clinical features of chronic Hep B?
Range of no symptoms to end stage liver disease
(ALT, Jaundice, hypoalbuminemia, coagulopathy, etc.)
429
What are goals of Hep B treatment?
Prevent cirrhosis and HCC
430
What are first-line agents for Hep B infection?
Lamivudine
Adefovir
Entecavir
Peg-IFNα2a
Telbivudine
Tenofovir +/- emtricitabine
431
What is the most common cause of chronic viral hepatitis in Asia and Africa?
Hepatitis B
432
What can diagonse Hepatitis B infection?
HBsAg
433
What is the incubation period of hepatitis C?
50 days (1-2 months)
434
What is the most sensitive indicator of Hepatitis C infection?
HCV RNA
435
Where does Hepatitis C replicate?
Hepatocytes
436
What is the most common genotype of hepatitis C in the US?
genotype 1
437
How is hepatitis C acquired?
percutaneous (perinatal and sexual
Transfusions
438
What is the most common cause of chronic viral hepatitis in the USA and Europe?
Hepatitis C
439
What is more effective at establishing infection, IV drug use with Hepatitis C or HIV?
Hepatitis C - it is highly efficient (1:75 vs 1:300 of HIV)
440
What is the natural history of hepatitis C?
441
What are clinical features of chronic hepatitis C?
Similar to hepatitis B
Extrahepatic manifestations are seen more in hepatitis C - cryoglobulinemia, non-immune mediated
Antibody is present once exposure occurs (doesn't always mean chronic infection though = look at RNA level for that)
442
What laboratory value can help evaluate the presence of chronic hepatitis C infection and of response to treatment?
HCV RNA level
443
What is treatment for Chronic Hepatitis C?
Interferon monotherapy
Combination interferon + ribavirin (or pegylated interferon)
Protease inhibitors (telaprevir, boceprivir, simeprivir)
Polymerase inhibitors ( sofosubuvir)
444
What avenues of prophylaxis exist for hepatitis C?
No vaccine
Immune globulins aren't useful
(nothing, essentially)
445
What is the incubation period of hepatitis D?
60-90 days (2-3 months)
446
What is a requirement of hepatitis D virus for replication and expression?
Presence of Hepatitis B Virus
447
How can you be infected with hepatitis D?
Co-infeciton (simultaneously wiht HBV acutely)
Superinfectino (acute HDV in chronic HBV)
448
What is a serological marker of acute HDV infection?
IgM anti-HDV
449
What prophylaxis measures are available for hepatitis D?
Immunization against HBV
No known prophylaxis for those already with HBsAg
450
How do you treat Hepatitis D?
Interferon
451
What is the incubation period of hepatitis E?
40 days (~1 month)
452
What serologic markers do you see in acute hepatitis E infection?
IgM anti-HEV
(not routinely available though)
453
How is hepatitis E transmitted?
Fecal-oral
In india, asia, africa, central america - after contamination of water supply
Mostly in young adults
454
What are clinical sequellae of hepatitis E?
Fulminant hepatitis particularly in pregnant women
455
What population is particularly susceptible to negative consequences of Hepatitis E?
Pregnant women
456
When do you see chronic hepatitis E infection?
In immunosuppressed patients (post organ transplant, HIV, chemo)
457
How do you treat chronic hepatitis E?
Reduce immunosuppressive agent (remember, it is typically only seen in immunosuppressed)
Pegylated interferon, ribavirin
458
How do you manage hepatitis E?
good higene
459
How do you prevent hepatitis E spread?
No antiviral therapy available, vaccines are recently tested, but nothing yet
460
What is jaundice?
Physical sign noted when bilirubin level is elevated (\>2.5 mg/dL)
461
What can cause jaundice?
Increased bilirubin production
Impaired hepatic handling
Benign laboratory finding
462
What is bilirubin?
End-product of metabolic degradation of heme
463
What are sources of bilirubin?
70-90% comes from erythrocytes (senescent, injured, ineffective erythropoiesis, hematomas)
Remainder comes from turnover of non hemoglobin hemoproteins (myoglobin, cytochromes, catalases)
464
How is bilirubin found in plasma?
bound to albumin - unconjugated is insoluble in plasma
Total bilirubin - 1-1.5 mg/dl (90% unconjugated, 10% conjugated)
465
What are the four steps of bilirubin transfer from blood to bile?
Hepatocellular uptake
Intracelular binding
Conjugation
Excretion of conjugates into bile canaliculus
466
What happens to bilirubin in the intestines?
No absorption in gallbladder/intestine
Terminal ileum/colon - hydrolysis to unconjugated bilirubin and reduction to complex tetarpyrroles (urobilinogen) by colonic bacteria; this is either excreted in feces (most), or re-enters enterohepatic circulation; small amount is excreted in urine
467
How is bilirubin processed in the kidneys?
Unconjugated bilirubin is not excreted into urine
Conjugated bilirubin is filtered at glomerulus
Bilirubinuria indicates presence of conjugated bilirubin in plasma, thus hepatobiliary dysfunction
468
What is dark urine a sign of?
Conjugated bilirubinuria (bilirubinemia)
469
What is direct bilirubin?
Conjugated
470
What is indirect bilirubin?
Unconjugated
471
What are causes of unconjugated hyperbilirubinemias?
Increased production
Reduced hepatic clearance
Inherited disroders of metabolism
472
What can cause an increase of production of bilirubin?
hemolysis, hematomas, ineffective erythropoiesis
473
What are causes of reduced hepatic clearance?
Neonatal jaundice
Breast milk jaundice
Drugs (rifampicin, chloramphenicol, gentamicin)
474
What are common inherited disorders of bilirubin conjugation?
Gilbert's syndrome
Crigler Najjar syndrome (type I and type II)
475
What is Gibert's syndrome?
MOst common hereditary hyperbilirubinemia
UGT1A1 Mutation - 10-33% of normal enzyme activity
Males\>females
Mild chronic or recurrent **unconjugated** hyperbilirubinemia
Typically can be benign
476
What is Crigler-Najjar Syndrome Type I?
Mutation in common exon of UGT1 complex
no functional enzyme activity
Appears neonatally, with severe neurological impairment - often fatal
(Rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of red blood cells. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants.)
477
What is Crigler-Najjar Syndroem Type II?
Mutations of UGT1A1
Markedly reduced but detectable enzyme activity
treated with phenobarbital to induce UGT enzyme activity
478
What differentiates Crigler-Najjar Type I and type II?
No enzyme UGT activity = Type I; Some activity = Type II
479
What is kernicterus?
Bilirubin staining of basal ganglia, pons, and cerebellum resulting in neuronal toxicity
480
What is Dubin-Johnson syndrome?
Mutations in gene encoding for canalicular transporter - have global defect in organic anion transport
Chronic intermittent jaundice with grossly pigmented liver
See scleral icterus, moderately enlarged/tender liver
Plasma bilirubin is 2-5 mg/dl (normal liver enzymes)
CONJUGATED hyperbilirubinemia
481
What is Rotor's Syndrome?
Unknown mutation
total bilirubin \< 10 mg/dl
Benign course with normal life expectancy
Only difference from Dubin-Johnson is the lack of pigmented liver that is seen in Dubin-Johnson
482
How does chronic liver injury result in hyperbilirubinemia?
Injury causes less efficient capacity to tranpsort bilirubin
End up with conjugated hyperbilirubinemia
483
How does intrahepatic cholestasis of pregnancy cause conjugated hyperbilirubinemia?
Occurs during 2nd or 3rd trimester
Elevated ALT in addition to bilirubin, as well as bile acids
Disappears after delivery, but may recur with subsequent pregnancies and with oral contraceptives
Unclear mechanism of action
484
What type of hyperbilirubinemia does biliary obstruction cause?
Conjugated
Choledocholithiasis
Neoplasms
Extrinsic compression
Inflammation/infection
485
How do you approach hyperbilirubinemia?
486
What lab tests are markers of hepatocyte integrity?
AST- Aspartate aminotransferase
ALT - Alanine aminotransferase
487
What are lab test markers for cholestasis?
Bilirubin
Alkaline phosphatase
Gamma glutamyl transpetidase (GGT)
5' Nucleotidase (not used anymore)
488
what are tru markers of liver function?
Albumin
prothrombin time or INR
489
What does acute hepatocellular injury look like on labs?
Elevated ALT/AST
Normal-to-elevated alkaline phosphatase, GGTP
Elevated total bilirubin
Normal PT and Albumin
490
What lab tests are useful for diagnosis cirrhosis?
Elevated prothormbin time
Decreased albumin
491
What is the classic lab finding in alcoholic hepatitis?
2 to 1 ratio of AST over ALT
