GI Deck 3 Flashcards
1
Q
17 year old male presents to his PMD with yellow eyes. No recent sexual contact, IVDA, or ETOH. On no medications. Similar episode 2 yrs ago.
Physical exam: +Scleral icterus. No stigmata of chronic liver disease. No hepatosplenomegaly or ascites
Labs:
Normal CBC and SMA-7
AST=25 (normal)
ALT=30 (normal)
Alk phos= 50 (normal)
Total bilirubin= 5.0 (elevated) Indirect bilirubin = 4.5 (elevated)
A
Gilbert’s Syndrome
2
Q
45 year old female presents with intermittent right upper quadrant pain, nausea, vomiting for 2 days. Low grade fever. History of occasional RUQ pain in past but never so bad or associated with nausea and vomiting. Noticed that 2 days ago her stool become more pale and her urine got darker.
Physical exam: BP=150/90; HR=110; +Scleral icterus. No stigmata of chronic liver disease, normo-active bowel sounds, moderate RUQ tenderness. No rebound or guarding. No hepatosplenomegaly
Labs:
AST=50 (normal)
ALT=52 (normal)
Alk phos=290 (elevated)
Total bilirubin = 6.0 (elevated) Direct bilirubin = 5.0 (elevated)
A
Obstruction - alk phos elevated, conjugated hyperbilirubinemia
Most commonly a stone
3
Q
35 year old male presents with RUQ pain, nausea, and vomiting for 3 days. No associated diarrhea. Recent unprotected sexual contact.
Physical exam: No scleral icterus. Mild RUQ discomfort; otherwise normal.
Labs:
AST=2000 (markedly elevated)
ALT=3000 (markedly elevated)
Alk phos=99 (normal)
Total bilirubin=3.0 (slightly elevated)
A
Viral hepatitis
4
Q
40 year old male presents to the ER with fever and jaundice. He just lost his job and his wife left him.
Physical exam: +scleral icterus and jaundice, otherwise normal.
Labs:
WBC=20K (elevated)
AST=200 (elevated)
ALT=50 (slightly elevated)
Alk phos=150 (slightly elevated) GGTP=300 (elevated)
Total bilirubin=15 (elevated)
A
Alcoholic Hepatitis
5
Q
What is the blood supply of the liver?
A
Dual - portal vein (60-70%) and hepatic artery (30-40%)
6
Q
What is the outflow blood supply of the liver?
A
IVC
7
Q
What is the path of the biliary system?
A
Drain bile fromed by hepatocytes that is secreted inot bile canaliculi
Into canals of Herig
Into intrehepatic and extrahepatic bile duts
8
Q
What is the blood supply of the bile ducts?
A
Hepatic arteries via peribiliary plexus of capillaries
9
Q
What are the components of the portal tracts?
A
Bile duct, portal vein, hepatic artery
10
Q
What are the central venules (terminal hepatic venules)?
A
Drain blood from sinusoids
11
Q
What are kupffer cells?
A
Special macrophages of the liver
12
Q
What can precpitate hepatocellular injury?
A
Oxygen deprivation (hypoxic or ischemic)
Chemical or drug injury (e.g. acetaminophen)
Infection (hepatitis)
Immunoligcal (autoimmune)
Genetic misprograming (storage disorder)
Metabolic imbalance (Fatty liver disease)
13
Q
What is ballooning degeneration/
A
Hepatocyte swelling (Volume change)
The result of severe cellular injury, can cause cell death
Clumped cytoplasmic organelles and large clear spaces
14
Q
What do we see here?
A
Ballooning degeneration
15
Q
What is steatosis?
A
Accumulation of triglyceride fat droplets within hepatocytes
Microvesicular - multiple tiny droplets that don’t displace nucleus (pregnancy, valproic acid toxicity)
Macrovesicular - single large droplet that displaces the nucleus (obesity, diabetes)
16
Q
What does cholestasis look like pathologically?
A
Looks like ballooning degenration, but rather feathery
Bile flow impaired, results in jaundice
Have a foamy cytoplasm
Obstruction, bile duct disease, viral hepatitis, toxic injury
17
Q
What do we see here?
A
Cholestasis. Note hte feathery appearacne
18
Q
What are gross features of acute hepatitis?
A
Capsule is edematous and tense
Liver is swollen and red
Focal depressions due to subcapsular necrosis and collapse
Bright yellow or green
In fulmanant hepatitis, the liver is shunken and soft, and the capsule is wrinkled
19
Q
What do we see here?
A
Acidophilic bodies that are indicative of apoptosis
20
Q
What areas of the liver are most susceptile to necrosis in ischemic injury?
A
Centrilobular zones
21
Q
What do we see pathologicallyi n hepatitis?
A
INjury associated with influx of acute or chronic inflammatory cells
Apoptotic hepatocytes, scavenger macrophages, lobular and portal inflammation
22
Q
What do we see here?
A
HEpatitis
23
Q
What is the difference between fulminant and subfulminant hepatitis?
A
Fulminant - develops within 2-3 weeks and results in massive hepatic necrosis
Subfulminant - less rapid course may extend up to 3 months, submassive
most due to viral hepatitis, rest due to drug or chemical toxicity
24
Q
What is interface hepatitis?
A
Inflammatory cells extend beyond the margins of the protal tract connective tissue - spill over into adjacent limiting plate nad beyond
Portal tract with irregular borders
25
What are the two mechanisms of liver regeneration?
Adult differentiated hepatocytes unergo division and replication
Extensive hepatic necrosis stimulates proliferation of progenitor cells (canal of herig = reserve compartment). In this way, you see the ductular reaction below
26
What are key events in liver fibrosis?
Stellate cells
Extracellular matrix deposition
Alteration of the parenchymal microvasculature
In cirrhosis, excess type I and III collagents are laid down not only in portal tracts but also in the lobule, creating delacate or broad septal tracts
Generally irreversible
27
What collagents are laid down too much in cirrhosis?
Collagen I and III
28
What is this?
Cirrhosis
Excess type I and III collagen laid down
29
A 45 year old man was incidentally found to have elevated transaminases. Further work-up revealed +HCV antibodies. He reveals that he experimented with illicit drugs 25 years ago. A liver biopsy is performed.
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Chronic hepatitis C, grade 2, stage 2
Steatosis
30
What does the grade of chronic hepatitis indicate?
Degree of inflammation - foci of parenchymal necrosis and apoptotic bodies
31
What odes the stage of chronic hepatitis indicate?
Degree of fibrosis (portal fibrosis, fibrous septa, bridging fibrous septa, transition into cirrhosis, cirrhosis)
32
48 yo female with abnormla liver enzymes:
AST 350, ALT 270
 + ANA 1:320
\*Liver biopsy was performed
 
Autoimmune hepatitis
33
What is a useful menomonic for remembering hte hepatitides?
A = always acute
B = bloodborne
C = chronic
D = double (requires B)
E = epidemic
34
What is ALD?
Alcoholic Liver Disease
Most common cause of cirrhosis in western world
MOre common in men than women
35
How does alcohol consumption relate to ALD
Continued alcohol ingestion once alcohol liver injury is present (converse is true, abstinence allows improvement)
Positve correlation between average per capita consumption of alchol and frequency of cirrhosis
Amount ingested and duration of intake correlate with incidence of ALD
36
How does Gender play a role in ALD?
Gastric mucosal alcohol dehydrogenase activity is lower in women, so there is greater hepatic exposure to ingested alcohol in women
HCV or HBV infection worsens ALD
Risk of liver injury increases above a threshold level of 80 g/day for men and 20 g/day for women
37
How do you screen for alcohol problems?
CAGE questions
38
Does the type of alcohol consumed influence the likelihood of developing hepatotoxicity?
Nope!
39
What are physical signs that can be seen in ALD?
Jaundice
Spider nevi
Hepatomegaly
Splenomegaly
Spider nevi are these:
40
What is this?
Spider nevi - seen in ALD
41
What lies on the spectrum of liver disease in patients who drink alcohol?
Normal, fatty liver, alcoholic hepatitis, cirrhosis
42
What is alcoholic steatosis?
Consequence of alcohol oxidation
Excess lipid is stored in large droplets within individual hepatocytes
Generally considered a benign, reversible condition
43
What od we see here?
Alcoholic steatosis
44
What are features of alcoholic hepatitis?
COmbination of steatosis, hepatocellular necrosis, and acute inflammation
Most pronounced in zone 3 of hepatic acinus
Eosiniophilic fibrillar material (mallory's hyaline bodies) in ballooned hepatocytes
Focally intense lobular infiltration of polymorphonuclear leukocytes
45
What do we see pathologically in cirrhosis/
Deposition of collagen around terminal hepatic veina dn along sinusoids
Characteristic chicken-wire pattern of scarring
Chronic alcohol use impairs normal regenerative response resultin gin small nodules of regenerating parenchymal and micronodular cirrhosis
Abstinence is associated with development of macronodular cirrhosis
46
What do we see here?
Cirrhosis
47
What do we see here? 
Micronodular cirrhosis
48
What therapy is available for patients iwth ALD?
Discontinue alcohol use and resume nutritious diet
Enroll pt in detox proram
Hospitalize for complications of electrolyte abnormalities, cardiac dysfunction, pacnreatitis, hemorrhagic gastropathy, major alcohol withdrawal syndromes, and infection
No specific drug therapies
Perhaps liver tranplant - if compliant and abstinent
49
What is NAFLD?
Non-Alcoholic Fatty Liver Disease
Most common liver abnormality in US
mimics clinical nad histological features of ALD
Hepatic manifestation of metabolic syndrome
50
What is along the spectrum of NAFLD?
NAFL - Steatosis
+ inflammation, ballooning, fibrosis, mallory's hyaline, megamitochondria
NASH: Cirrhosis (cryptogenic, HCC)
51
What is necessary for a diagnosis of NASH?
Histology - steatosis, macro\>micro, zone 3 predominant
Lobular inflamation
Hepatocellular ballooning, usually zone 3
May see perisinusoidal fibrosis, glycogenated nuclei, acidophil bodies, Mallory's hyaline, iron, megamitochondria
52
What are outcomes of NASH?
16% improve
43% stable
41% progress
53
What are diseases that are commonly associated with NAFLD?
Diabetes - 40%
Obesity - 40-100%
hyperlipidemia - up to 80%
54
What are pathophysiological features of NAFLD?
Insulin resistance
Increased adiposity
55
How can NAFLD present?
Asymptomatic with liver enzyme elevation or fatty liver on imaging (common)
Hepatomegaly, fatigue
Decompensated cirrhosis, HCC (rarely)
56
How do you diagnose NAFLD?
History- \< 20g alchol per day
Labs - ALT\> AST, elevated triglycerides, insulin resistance
Imagin - ultrasound, CT, MRI,
57
How do you treat NAFLD?
Control risk factors (weight loss, lipid control, diabetes control, abx for bacterial overgrowth)
58
How do you distinguish ALD and NAFLD?
By history - NAFLD = \< 20g alcohol consumption per day
59
What is PBC?
Primary biliary cirrhosis
Mostly women, mean age 50 years (wide range)
All races/nationalities
Variations in prevalence
Unknown etiology
60
How do you diagnose PBC?
Elevated Alk/Phos/GGTP (cholestatic pattern)
Anti-mitochondrial antibodies (AMA) in 95%
Elevated serum IgM
Elevated cholesterol (in 75%)
Histologic confirmation - "florid duct lesion"
61
What do you see here?
Florid duct lesion
Indicative of PBC - primary biliary cirrhosis
62
How do patients with PBC present?
Abnormal liver biochemistries
Symptoms of pruritis, fatigue
Signs and symptoms of advanced liver disease
63
What physical exam findings do you see in primary biliary cirrhosis?
Hepatomegaly (50%)
Splenomegaly (30%)
Jaundice - late finding
Xanthomas
Xanthelasma
Butterfly pigmentation
64
What are diseases associated with PBC?
85% have other autoimmune diseases
65
What is PSC?
Primary sclerosing cholangitis
66
What are secondary causes of sclerosing cholangitis?
AIDS cholangiopathy
Bile duct neoplasm
BIliary tract surgery
Choledocholithiasis
Congenital
Ischemic injury of duct
Caustic injruy (chemo)
67
Who gets PSC more?
Males, 25-45 years old
68
What is the pathogenesis of PSC?
Unknown - immune mediated (HLA-B8, HLA-DR3, HLA-Drw52A)
Hypersensitivity reaction - exposure to toxic bile acids within intestines or ischemic injury
CMV or cryptosporidium infection - inflammatory response to chronic or recurrent infection inp ortal circulation
69
How do patinets with PSC present?
Asymptomatic elevation of LFTs
Pruritis
Cholangitis (fever/chills/RUQ pain/jaundice)
Signs of advanced liver disease
Cholangiocarcinoma (as a result of chronic inflammatory process)
70
How do you diagnose PSC?
Elevated Alk Phos/GGTP
No specific antibody test (pANCA, anti SMA, positive ANA) not in ALL, but in most
Cholangiogrpahy - intrahepatic and extrahepatic ducts
Liver biopsy shows onion skin fibrosis around bile ducts
71
What disease has characteristic onion skin fibrosis around the bile ducts?
PSC
72
What do you see here?
PSC - primary sclerosing cholangitis
73
What od you see here?
Onion skin fibrosis aroudn bile duts - Primary sclerosing cholangitis (PSC)
74
What diseases are associated with PSC?
IBD - in many
Other immunoligcal diseases
75
What are complicaitons of PSC?
Cholangitis
End stage liver disease
Cholangiocarcinoma
Risk of colon cancer increased 10x
76
How do you treat PSC?
Resect - avoid surgery
Dilate - dominant striture
Medication - ursodeoxycholic acid increases bile flow (Controversial)
Transplant
77
What is autoimmune hepatitis and who gets it?
More in women than in men
Early adulthood/adolescence/ perimenopausal women
What it sounds like
78
How does autoimmune hepatitis present?
Acute hepatitis (fever, chills, RUQ pain, jaundice)
Insidious - abnormal LFTs fatigue, aches
Advanced liver disease/liver failure
79
What are diagnostic criteria for autoimmune hepatitis?
Serum ALT/AST abnormalities
Serum gamma gobulin (IgG \> 1.5x nl)
ANA, SMA or LKM1 \> 1:80 in adults
Liver biopsy to rule out other lesions
Normal levels of alpha-1-antitrypsin, ceruloplasmin
Seronegativity for infectious etiologies
No parenteral blood exposure
Low ethalnol ingestion
No use of hepatotoxic drugs
80
How do you treat autoimmune hepatitis?
Long term immunosuppression (mainstay) - prednisone, azathioprine, mycophenolate mofetil (cellcept)
81
What diseases are associated with autoimmune hepatitis?
SLE, MG, ITP, Pernicious anemia, other autoimmune disease
82
What is Wilson Disease?
Rare inherited autosomal recessive disorder of copper metabolism (ATP7B Gene)
Causes absent or reduced funciton of ATPase - decreased hepatocellular excretion of copper in bile, resulting in accumulation of copper in hepatocytes
Cellular death, release into blood where it can deposit in brain, kidneys, and cornea
83
What do oyu see here?
Copper deposition associated with Wilson Disease
84
What is normal copper homeostasis?
Dietary copper is abosred by small intestine and transported to liver
Hepatocytes incorporate coppper into apoceruloplasmin to produce ceruloplasmin which gets secreted to blood
Copper also secreted to bile
85
What is copper homeostasis in wilson disease/
Mutaiton of ATP7B resutls in retention of copper in hepatocytes
Impaired incorporation of copper into ceruloplasmin so you get **low serum ceruloplasmin**
****
86
How does Wilson Dsease present?
Hepatic - 42% - Abnormal liver chemistries, Chronic hepatitis, Fulminant hepatic failure, cirrhosis
Neurologic - 34% - mild tremor, parkinson liek symptoms
Hematologic - 2% - hemolytic anemia
Psychiatric - 10% - depression, labile mood, frank psychosis
Rarely presents after 40 years old
87
What are kayser Fleisher rings?
Deposition of copper in eye
88
What do we see here?
Kayser Fleischer rings - Wilson's disease
89
How do you diagnose Wilson Disease/
Low serum ceruloplasmin
Kayser Fleisher rings
Urinary copper \> 100ug/24 hours
Hepatic copper \> 250ug/g dry weight
Genetic testing
90
How do oyu treat wilson disease?
First line - chelating agents (D penicillamine
Second line - zinc = blocks absorption
Diet - low copper
Liver transplant is curative
91
What is HFE-Hereditary hemochromatosis?
Iron overload
Genetic - autosomal recessive
Mutation is most commonly occuring genetic abnormalities in american population
92
What causes HFE hereditary hemochromatosis?
HFE gene mutaitons
93
WHat is the pathogenesis of HFE hereditary hemocrhomatosis?
Mutaiton in HFE causes altered HFE protein
Leads to impairment of iron sensing and absorption
Excess iron absorbed from GI tract
Iron deposits in liver, heart, pituitary and thyroid glands, pancreas, joints and gonads
94
What is normal iron homeostasis?
Dietary iron absorbed by duodenal enterocytes and exoprted itno blood by ferroportin
Circulates boudn to transferrin
Liver cell senses plasma iron and absorbs it via HFE/TFR2
HFE regulates synthesis of hepcidin
Hepcidin inhibits iron secretion by duodenum and release of iron by macrophages (neg feedback)
95
What is hemochromatosis iron homeostasis?
Defect in HFE results in less hepcidin produciton
MOre iron is absorbed and stored in macrophages
MOre iron gets transported and deposited by plasma tranferrin
96
What is the classic triad of HFE hereditary hemochromatisis?
Cirrhosis, bronze skin, diabetes
Cirrhosis - deposition in liver
Bronze skin - pituitary
Diabetes - pancreas
97
WHat is a serious sequella of HFC hereditary hemochromatosis?
Deposition of iron in heart - can cause CHF, arrhythmias
98
What do you see here?
Bronzed skin of HFC hemochromatosis
99
Why do women develop later onset of HFE Hereditary hemochromatosis?
Menstrual blood loss can artificailly deplete iron stores
100
How do you diagnose Hereditary hemochromatosis?
Fasting transferrin saturation \> 50% on two consecutive tests
Ferritin \> 1000 ng/ml
Genetic testing
MRI with liver iron quantification
Liver biopsy - parenchymal iron distribution, 3+ to 4+ stainable iron in liver
101
What is this a progression of?
Hemochromatosis
102
What do you see here?
Hemochromatosis
103
What is a difference between hereditary/primary and secondary hemochromatosis?
Iron deposits in reticuloendothelial cells
104
What do ou see here?
Secondary hemochromatosis - deposition of iron in reticuloendothelial cells
105
How do you treat hemochromatosis?
Screen family members
Phlebotomize blood once or twice per week to deplete iron stors
Maintenence phlebotomy to maintain low or low normal ferritin levels
106
What is the mortality associated with hereditary hemochromatosis?
Symptomatic have less survival rates
If phlebotomy is initiated before cirrhosis, can have simlar survivals
Liver transplats can help
107
What is cirrhosis?
end stage of any chronic liver diease
Characterized histologically by regenerative nodules surrounded by fibrous tissues
Clinically can be either **compensated** or **decompensated**
108
What lab results can suggest cirrhosis?
Liver insufficiency - low albumin, prlonged PT, high bilirubin
Portal hypertension (low platelet count)
AST/ALT ratio \> 1
109
What do you see on the right?
Cirrhosis
110
What is seen on the right?
Cirrhosis
111
What is hte progression/natural history of chronic liver dizease?
Chronic liver disease to compensated cirrhosis to decompensated cirrhosis to death
compensated to decompensated is characterized by development of complications (variceal hemorrhage, ascites, encephalopathy, jaundice
112
What is the most common source of complications from cirrhosis?
Portal hypertension
113
What is significant about the coronary vein wrt portal hypertension?
Feeds upper stomach and esophagus - varices
114
What, from a vascular perspective, causes portal hypertension?
Increase in resistance ot portal flow, or increase in portal venous inflow (P = RxF)
115
What occurs in cirrhosis that leads to portal HTN?
Increased intrahepatic resistance
116
What are causes of portal HTN?
Cirrhosis is most common cause
Site of increased resistance is sinusoidal
Other causes are classified acording to site of increased resistance (pre-hepatic, presinusoidal, post sinusoidal, post hepatic)
117
Where is the site of increased resistance in cirrhosis?
Sinusoids
118
What is the site of increased resistance in schistosomiasis?
Pre-sinusoidal
119
What is the site of increased resistance in portal or splenic vein thrombosis?
Pre-hepatic
120
What is the site of increased resistance in veno-occlusive disease?
Post-sinusoidal
121
What is the site of increased resistance in budd-chiari syndrome?
Post-hepatic
122
Why is portal hypertension a positive-feedback problem?
Backup causes splanchnic arterial vasodilation - this increases flow to the mesenteric veins and portal veins - causes hyperdynamic state
123
How does a hyperdynamic circulatory state arise in cirrhosis?
Splanchnic and systemic vasodilation that decreases arterial blood volume seen by kidneys - causes RAAS system to activate and increase sodium and water retention, this expands plasma volume, leading ot hyperdynamic circulation
124
What is the relationship between state of cirrhosis and prevalence of esophageal varices?
Worse = greater risk of varices
125
Which varices are more likely to rupture?
Larger ones
126
What is the treatment of medium/large varices without hemmorrhage?
β-blockers indefinitely
Endoscopic variceal ligation in patients intolerant to β-blockers
127
What is the treatment of small varices with no hemorrhage?
Surveillance
128
What is the treatment with variceal hemorrhage or recurren themorrhage?
Control hemorrhage
IV access and fluid resuscitation - don't overtransfuse
Antibiotic prophylaxis
Pharmacological threapy
Endoscopic therapy
Shunt therapy
129
What is the efficacy of endoscopic variceal band ligation?
Controls bleeding in 90%
Rebleeding in 30%
130
What is TIPS?
Transjugular Intrahepatic Portosystemic Shunt
131
What are gastric varices?
Bleedign in stomach - harder to manage, but still possible. Seen in portal hypertension
Endoscopic cyanoacrylate injection helps control bleeding (glue)
TIPS also controls bleeding
132
What is portal hypertensive gastropathy?
Endoscopic change seen in most portal HTN pts
May be mild or severe
Characterized by cobblestone appearance of mucosa
More proximal than distal
133
What is type A hepatic encephalopaty?
Associated with Acute liver failure (tylenol toxicity, etc.)
134
What is type B hepatic encephalopathy?
Associated iwth porto-systemic Bypass without intrinsic hepatocellular disease
135
What is type C hepatic encephalopathy?
Associated with Cirrhosis and portosystemic shunting
136
Why does cirrhosis cause hepatic encephalopathy?
(Type C)
Translocation of substances across bowel - protein load and bacterial products
Failure to metabolize these substances in liver - delivered directly to brain, can cause damage
Ammonia is pretty useless test, though
137
How do you diagnose Hepatic encephalopaty/
Clinical findings and history
Ammonia levels are unreliable (poor correlation) - NOT necessary
Number connection test
Slow dominant rhythm on EEG
138
What are the stages of hepatic encephalopathy?
139
What is asterixis useful for?
Finding hepatic encephalopathy
140
What physical exam maneuvers are useful for evaluating hepatic encephalopathy?
Asterixis
Number connection test,
Draw a star
Sample handwriting
141
What is minimal hepatic encephalopathy?
Occurs in 30-70% of cirrhotic patients without overt hepatic encephalopathy
Detected by psychometric and neuro-psychological testing
May improve with lactulose or synbiotics
142
How can you treat hepatic encephalopathy?
Identify and treat precipitating factor: Infection, GI hemorrhage, prerenal azotemia, sedatives,constipation
Lactulose (adjust to 2-3 bowel movements/day)
Protein restriction, short term if at all (not fully proven to be efficacious)
143
What is ascites?
Accumulation of fluid in the peritoneal cavity
144
What is the most common cause of ascites?
Cirrhosis
145
What are causes of ascites?
Cirrhosis
Peritoneal Malignancy
Heart Failure
Peritoneal TB
Pancreas, Budd Chiari, Nephrogenic
146
Where does the fluid in ascites come from?
Weeping liver - from the liver itself
147
Is portal vein obstruction enough to initiate ascites?
NO - need to have a bad liver
Portal HTN is not enough
148
Is hepatic vein obstruction enough for the initiation of ascites?
Yes, outflow block increases sinusoidal pressure which causes fluid to leak
149
How does ascites develop?
150
What is the SAAG?
Serum Ascites Albumin Gradient
151
What is a SAAG \> 1.1 indicate?
Source of ascites is hepatic sinusoids -\> Sinusoidal HTN or postsinusoidal HTN
152
What does a SAAG \< 1.1 indicate?
Peritoneal pathology (malignancy, TB)
153
How can you discern what the source of ascites is?
SAAG (\< 1.1 = peritoneum, \> 1.1 = hepatic)
154
What is a better therapeutic option for ascites, large volume paracentisis (LVP) or diuretics?
Both are equally efficacious - depends on lifestyle preferences
155
What is the most common iinfection in cirrhotic patients?
SBP - spontaneous bacterial peritonitis
156
What types of bacteria are responsible for SBP?
Gram negatives, more often than gram positives
157
Why does SBP occur?
Translocation of bacteria caused by:
Decreased immunity
Intestinal bacterial overgrowth (secondary to decreased transit time)
Increased permeability of intestinal mucosa
158
How do you diagnose SBP?
More than 250 PMN in ascitic fluid
159
How do you treat SBP?
IV cefotaxime, amoxicillin
Oral ofloxoacin (in uncomplicated)
Avoid aminoglycosides
At least 5 days
160
What does the development of renal failure indicate for the prognosis for a patient with cirrhosis?
Increased mortality rates
161
What is hepatorenal syndrome?
Renal failure in patients with cirrhosis, advanced renal disease and severe sinusoidal portal HTN in the absence of histological changes in kidney
162
What are the two types of hepatorenal syndrome?
Type 1 - rapidly progressive, doubling of creatinine to \> 2.5 or halving of creatinine clearance to \< 20ml/min
Type 2 - more slowly progressive, creatinine \> 1.5 mg/dl or clearance of creatinine \< 40 ml/min (associated iwth refractory ascites)
163
What two things are always present in patients with hepatorenal syndrome?
Ascites and hyponatremia
164
What do hyponatremia and ascites in the setting of liver disease and renal failure indicate?
Hepatorenal syndrome
165
How do you make a diagnosis of acute liver failure?
Coagulopathy (INR \> 1.5)
Encephalopathy
Jaundice \< 24 weeks duration
166
What are the two main subdivisions of acute liver failure?
Fulminant
Subfulminant
167
What are major etiologies of fulminant hepatic failure?
Viral - HAV, HBV +/- HDV, HEV, HSV, CMV EBV, VZ, Adenovirus, Hemorrhagic fever viruses
Drugs/toxins - Acetaminophen, CCl4, mushrooms, ecstasy, TB meds, ...
Vascular - Right heart failure, Budd-Chiari syndrome, shock liver, ...
Metabolic - Wilson's Disease, Pregnancy, Reye's
Misc - malignant metastases, autoimmune
Intermediate - graft non-function in transplanted
168
What ist he most common cause of liver failure in the US?
Acetaminophen
169
Why do patients iwth acute liver failure die?
Multi-organ failure - CV dysfunction, renal failure, Hypoglycemia, coagulopathy, infection/sepsis, cerebral edemam secondary to hepatic encephalopathy
170
What is the basis of hepatic encephalopahty?
Nitrogen load to gut causes increased NH3 to liver, and other metabolites
Sent up to brain, causes damage
171
What is the most dangerous sequellae of hepatic encephalopathy?
Cerebral edema - vasogenic and cytotoic
172
What is the cushing reflex?
Systemic hypertension with bradycardia - sign of cerebral edema (can be seen in acute hepatic failure)
173
What are signs of cerebral edema secondary to liver failure?
Cushing reflex
Decerebrate rigidity
Disconjugate eye movements
Loss of pupillary reflexes
174
How do you monitor cerebral edema in liver failure?
ICP
Cerebral perfusion pressure
175
What are coagulopathies seen in acute liver failure?
Decreased synthesiss of factors II, V, VII, IX, and X
Factor V has short halflife and is a good reflection of liver function
176
Why do you have infection/sepsis in acute liver failure patients?
Kupffer cell malfunction, neutrophil malfunction and cell mediated immunity dysfunction
Risk increases with time in ICU
Gram + organisms more common than gram -
Fungal infections after 2 weeks in ICU
177
What is a cardiovascular sequellae of liver failure?
Low systemic resistance and pulmonary resistance
INcrease in Cardiac outupt increases metabolic rate which causes oxygen debt and relative hypotension and tachycardia --\> lactic acidosis
178
What are metabolic symptoms seen in acute liver failure patients?
Hypoglycemia - defective gluconeogenesis and inadequate uptake of insulin
179
How do you treat acute liver failure?
Depends on etiology
180
What is the treatment for tylenol overdose?
N-Acetyl Cysteine
181
What is Hy's Law?
Aminotransferase elevation accompanied by bilirubin elevation carries a worse prognosis than aminotransferase elevation alone
LFT elevation + bilirubin elevation = worse than LFT elevation alone
182
What are predictable vs idiosyncratic hepatotoxins?
Preidctable = dose dependent, reproducible, high incidence, short latency, absent extrahepatic involvement
Idiosyncratic = not dose dependent, poorly reproducible, low incidence, variable latency, can have extrahepatic involvement
183
What are the three phases of hepatic biotransformation of drugs?
Oxidation (Phase I) - CYP
Conjugation (Phase II) - Transferases
Excretion (Phase III)
184
What are CYP inducers?
Rifampin
Phenytoin
Carbamazepine
Phenobarbital
Dexamethasone
Alcohol
185
What are CYP inibitors?
Grapefruit Juice
Erythromycin
Clarithromycin
Ketoconazole
RItonavir
186
What are three forms of alcoholic liver disease?
Hepatic steatosis
Alcoholic Hepatitis
Alcoholic cirrhosis
187
What defines hepatic steatosis?
Large, fatty liver
Microvesicular or macrovesicular
Hepatomegaly, High serum bilirubin, alk. phos
188
What is microvesicular vs macrovesicular?
Macro - one single vacule with mucus pushed to the side
Micro - nucleus stays in the center, and you see multiple vacuoles
189
What do you see here?
Hepatic steatosis
190
What are symptoms of alcoholic hepatitis?
Non-specific or cholestatic
191
what are lab findings in alcoholic hepatitis?
Hyperbilirubinemia, high alkaline phosphatase, leukocytosis
192
What does hyperbilirubinemia, high alk. phos, and leukocytosis indicate?
Alcoholic hepatitis
193
What do you find pathologically in alcoholic hepatitis?
Hepatocyte swelling adn necrosis (ballooning)
Mallory-Denk bodies - tangled skeins of cytokeratin filaments
Neutrophilic reaciton (lobular inflammation)
Fibrosis
194
What do we see here?
Mallory-Denk bodies (Mallory's hyalines)
Indicative of alcoholic hepatitis
195
What is the final and irreversible stage of alcoholic liver disease?
Alcoholic cirrhosis
196
What are findings in alcoholic cirrhosis?
Yellow-tan, fatty enlarged liver turns into a **brown, shrunken, non-fatty liver**
****
197
What are vascular disorders of the liver?
Passive congestion (acute - failing heart in agonal period; chronic - CHF)
Shock
Infarction
198
Where in the lobular architecture of the liver do you find ischemic necrosis?
Centrilobular hepatocytes
199
What is veno-occlusive disease?
Fibrous occlusion of small hepatic venules \< 1mm in diameter with secondary parenchymal congestion
200
What do you see on the left?
Veno-occlusive disease
201
What can cause veno-occlusive disease?
Pyrrolizidine alkaloids (\>150 plants) - abdominal pain, ascites, hepatomegaly; chronic w/ portal HTN, or hepatic failure
After BM transplantation
Hepatic radiation adn chemotherapeutic drugs (azathioprine)
202
What signs/symptoms will you see in a patient with veno-occlusive disease due to pyrrolizidine alkaloids?
Acutely - abdominal pain, ascites, hepatomegaly
Chronic - portal HTN, hepatic failure
203
What signs/symptoms will you see in a patient with veno-occlusive disease after bone marrow transplantation?
54% are symptomatic
3 weeks after treatment, present wtih weight gain, thrombocytopenia, jaundice, hepatic failure
204
What is on the differential diagnosis when considering veno-occlusive disease?
Constrictive pericarditis
CHF
Hepatic vein thrombosis (Budd-Chiari Syndrome)
Sickle cell disease
205
What is caudate lobe (of the liver) hypertrophy indicative of?
Budd-Chiari Syndrome
Pretty reliable
206
What can cause Budd-Chiari Syndrome?
Hypercoagulable states
Stasis or mass lesions (HCC, membranous obstruciton of IVC)
Vascular injury (trauma, vasculitis, sarcoidosis)
IBD, connective tissue disease, Multiple Myeloma, etc..
207
What are features of hepatic adenoma?
Solitary, well-demarcated mass, encapsulated
Microscopically - resemble normal hepatocytes, BUT portal tracts, central venules are ABSENT, and arteries and veins traverse the tumor
Associated with oral contraceptive use
208
What liver lesions are solitary, well-demarcated masses that are encapsulated. They also have absent portal tracts and central venules, and are associated with oral contraceptive use. More than 1 may be present?
Hepatic adenoma
Hepatic adenomatosis is if there are \> 10 lesions
209
What is focal nodular hyperplasia (FNH)?
Benign hepatocellular lesion
Can be of any size, and can be solitare or multiple
Can be associated with hemangiomas or hepatocellular adenomas
Doesn't bleed or transform into HCC
can be seen in both normal or fatty liver
210
Does FNH transform to HCC?
NO
211
What do you see here?
Focal nodular hyperplasia
212
What do you see here?
Focal Nodular Hyperplasia
213
What is nodular regenerative hyperplasia (NRH)?
Can cause non-cirrhotic portal HTN
Compression of liver cell plates in between hyperplastic nodules (crowding of reticulin fibers)
Occurs in many systemic conditions - MPD, collagen vascular disease, medications (early antiretrovirals)
214
What is a hemangioma?
Benign vascular tumor
Most common tumor in the liver
215
What is this?
Hemangioma
Benign vascular tumor
MOst common ltumor in the liver
216
What type of tumors are most common in the liver?
Secondary (mets)
217
What is the most common metamstases to the liver?
Colon cancer
218
This was taken from the liver, what do you suspect?
Metastatic colon cancer
219
What are the primary liver tumors?
HCC (hepatocellular carcinoma)
Cholangiocarcinoma
Angiosarcoma
220
What viral infection does HCC have a strong association with?
HCV
HBV
221
What are common causeso fo HCC?
HBV
HCV
Aflatoxin B
Alcohol
Rare: contraceptive and anabolic steroids; metabolic disease; storage disease; vinyl chloride; old age
222
What is this?
HCC
223
What do HCC look like grossly?
Soft, hemorrhagic, tan masses
224
What does HCC look like histologically?
Look like benign hepatocytes, but can be varying
Can produce Bile
225
What is cholangiocarcinoma?
BIle duct carcinoma
Gland-forming (adenocarcinoma)
Arises from biliary epithelium
Strong association with PSC
226
What is a klatskin tumor?
Hilar tumor of the biliary tree (cholangiocarcinoma
At the convergence of right and left hepatic ducts
Causes obstruction
227
What is an intrahepatic cholangiocarcinoma?
Cholangiocarcinoma that occurs at more distal sites (not at the common biliary tree)
228
What is an angiosarcoma?
Malignant vascular tumor
Multiple hemorrhagic nodules
229
What is htis?
Angiosarcoma of liver
230
What is this?
Bile duct cyst
231
What is the most common presentation of cystic fibrosis patients in pediatric settings?
Failure to thrive
232
Why do children typically fall off the weight curve (have poor weight gain)?
Not typically malabsorption
Typically poor caloric intake - picky eaters, parents feedign 'low fat diet'
233
When do you begin a malabsorption workup on a child?
When a child takes in more calories but still does not gain weight
234
What are routine tests for malabsorption workup?
Calorie count
72 hour fecal fat
serum d-xylose
blood for CBC, chem screen, CRP, ESR, and celiac antibodies
235
What are you thinking in a child with abnormal fecal fat and normal d xylose?
Pancreatic insufficeincy, such as cystic fibrosis
236
What are you thinkin in a child with positive fecal fat with abnormal d-xylose?
Villous damage (Crohns, Celiac, allergy, autoimmune enteropathy, short gut syndrome)
237
What is cystic fibrosis?
Autosomal recessive disease
1:2500 in caucasians
Chromosome 7
CFTR gene - transmembrane conductance regulator
238
What is the most common Cystic Fibrosis mutation?
ΔF508
2/3 of mutations
239
What is the funciton of CFTR?
Controls flow of H20 and ions in and out of cells
CFTR impaired function causes lack of ion flow
CFR is found in epithelial cells of lung, liver, pancreas, GI and reproductive
**Moves chloride out and sodium in**
240
What is the result of CFTR mutations?
Cause epithelium to produce abnormally thick, sticky mucus that can cause obstructions
241
What is a sweat test useful for?
CFTR defect identification -
CFTR mutations don't allow for reabsorption of sodium in sweat glands - get sweatty salt
242
How do most cystic fibrosis patients present?
Pancreatic insufficiency in 85%
243
What are GI issues seen in Cystic Fibrosis?
Pancreatic insufficiency
Meconium ileus
Distal intestinal obstruction syndrome
INtestinal atresia
Rectal prolapse
244
What is meconium ileus?
Bowel obstruction wihtin first 48 hours of life
Meconium obstructs the terminal ileum, resulting in abdominal distention and bilious vomiting
 
245
What is distal intestinal obstuction syndrome?
In older patients, similar to meconium ileus
Can present as abdominal pain, constipation, bloating
246
How does cystic fibrosis cause rectal prolapse?
Passage of large, bulky stools - can be due to pressing down and increased effort
Can often be presenting sign
247
What are liver conditions seen in cystic fibrosis?
Biliary fibrosis/cirrhosis
Portal Hypertension
Cholestasis
248
Why does cystic fibrosis cause liver disease?
Thickened secretions/bile blocks bile ducts leading to cholestasis
Cholestasis leads to inflammaiton, fibrosis and cirrhosis
Present with signs of portal HTN - hepatosplenomegaly, hypersplenism, variceal hemorrhage
249
What is extra-hepatic biliary atresia?
Most common structural cause for neonatal jaundice
Abnormal LFTs
Abnormal physical exam: failure to thribe, jaundice, abndominal distension, +/- hepatosplenomegaly
250
What is the most common structural cause for neonatal jaundice?
Extrahepatic biliary atresia (EHBA)
251
What is the natural history of extrahepatic biliary atresia (EHBA)?
End stage liver disease - most common cause of transplants in children (liver)
252
What casues extrahepatic biliary atresia?
Unknown - infectious? autoimmune? vascular accident?
253
How do you diagnose extrahepatic biliary atresia?
Sonogram
hepatobiliary scan (HIDA) - most sensitive
Liver biopsy
Intraoperative cholangiogram
254
What is HIDA?
Hepatobiliary scan - with technecium 99
Good to identify extrahepatic biliary atresia
255
What do you see on biopsy of a patient with extrahepatic biliary atresia?
Cholestasis - bile plugs
Fibrosis with or without cirrhosis
Bile ductular proliferation
Inflammation
256
How do you treat extrahepatic biliary atresia?
Portoenterostomy - excision of obliterated extrahepatic ducts and attachment of small bowel to porta hepatis to act as biliary conduit
A bridge to liver transplant
257
What is the most common cause of constipation in children?
Stool witholding - control, fear
258
What do you worry aobut if a pateint doesn't respond to constipation treatment?
Hirschsprung's Disease
Or if infant doesn't pass meconium within first 24-48 hours of life, you must rule out Hirschsprung's disease
259
What is Hirschsprung's Disease?
Most common cause of lower intestinal obstruciton in neonates
Males more than females
More commin in Down Syndrome
Delay of passage of meconium - constipation - abdominal distention - vomiting - perforation - enterocolitis
260
What causes Hirschsprungs disease?
Failure of craniocaudal migration of ganglion cell precursors along GI tract
Absence of Meissner's and Aurbach's plexus causes lack of parasympathetic input - lack of relaxation
Results in obstructive symptoms
261
How do you diagnose Hirshsprung's disease/
Barium enema - look for transition zone
Rectal biopsy - check for presence or absence of ganglion cells
Normal biopsy:
262
How do you treat Hirschsprung's disease/
Surgery - resection of aganglionic segment and then pull through rest of bowel to rectum
Must make diagnosis early to prevent eneterocolitis - bacterial translocation
263
What is the largest immune cell reservoir in the body?
The gut
264
How does antigen uptake occur in the GI tract?
Direct sampling by dendritic cells
Particulate antigens sampled by M cells (Peyer's patches)
Soluble antigen by transcellular (normal) or paracellular (inflammatory) mechanisms
265
How do immune cells home to the gut?
Vitamin A is metabolized by resident GI dendritic cells, which induces integrin α4β7 on T and B cells during induction
They can then home back
Vitamin A deficiency leads to mucosal infections
266
How do commensal bacteria fight off pathogenic bacteria?
Out competing
Inducing production of antimicrobial peptides
Inducing immune cell proliferation/specification
267
What is oral tolerance?
Oral presentation before skin contact for immunization (tolerance development) causes less of a hypersensitivity reaction upon second exosure
268
What is the major Ig in mucosal sites?
IgA 
269
What allelic variants are associated with Crohn's Disease?
NOD2
270
How do NOD2/ATG16L defects lead to increased inflammatory states of mucosa?
Lead to defective bacterial sensing, defective defensin production and persistent intracellular bacteria
271
What infection are gut bacteria uniquely susceptible to?
HIV-1
CCR5 expressing cells
272
What are mechanisms of GI defense against infection?
Gastric acid secretion (pH \< 4 is bacteriocidal - PPIs may be increasing risk of C. diff)
Intact small bowel motility
Mucous secretion by enterocytes
Secretion of IgA
273
What is a common feature of bacterial dysentery?
Enteroinvasion
274
What are common features of enteroinvasion?
Bloody, mucopurulent stools
Signs and symptoms of inflammation (abdominal pain, fever, fecal leukocytes, leukocytosis)
275
What are common organisms implicated in dysentery?
Shigella
Campylobacter
Yersinia
Enteroinvasive E. coli
Enteroinvasive salmonellosis
276
What are features of toxin-induced diarrhea?
NO cellular invasion
Stools not bloody, not purulent, no fecal leukocytes
Toxins released by adherent organisms or preformed toxins (vibrio cholera, enterotoxigenic e. coli)
277
What are mechanisms of action of toxin induced diarrhea?
cAMP
cGMP
Calcium channels
INterfere with Na driven absorption and stimulates chloride driven secretion
278
What are mechanisms/examples of infection induced diarrhea?
C diff, enterohemorrhagic e. coli, enterotoxic e. coli
Features include cell injury, inflammation, intestinal secretion
279
What is a difference between organisms with preformed toxins and those without, with respect to toxin-induced diarrhea?
Preformed toxins - do not require adhesion
280
How does shigella present?
Invasive organism - mostly colonic, with scattered terminal ileal ulceration
Enteroadherence with release of toxin may precede enteroinvasion - may have watery diarrhea prior to teh dysentery
Doesn't usually penetrate beyond mucosa - bacteremia is rare
281
What is this?
Infectious colitis - not specific for given organism
282
How do you get non-typhoid salmonella?
Five F's
Food, fingers, feces, flies, fomites
283
Where does salmonella typically infect?
Terminal ilieum, less likely colon
May present as gastroenteritis or dysentery
284
What are risk factors for invasive non-typhoid salmonellosis?
immunosuppression
sickle cell anemia
schistosomiasis
reduced gastric acidity
Usually in terminal ileum, less frequently in colon
Bacteremia can lead to localized infections in joints, meninges, cardiac valves, bone
285
What are features of salmonella typhi/typhoid fever?
Invades small bowel mucosa, lamina propria, lymphatics, blood stream
Minimal intestinal systems
Systemic toxicity - high fevers, headaches, toxemia, mental status changes
Then pain localizes to right lower quadrant as organisms localize to Peyer's patches of ileum, which preceds diarreha, bleeding and perhaps even perforation
286
What is campylobacter jejunii?
Most frequent cause of bacterial infections
Chicken, human and other animals are most frequent carriers
Asymptomatic, watery diarrhea, dysentery
Highest diagnostic yield is with stool cultures
287
What is yersinia enterocolitica?
Favors invasion in right lower quadrant with acute onset that may **mimic Crohn's**
Most common in children, may **mimic appendicitis**
Source - milk, ice cream, pets, animal food products
Enteroinvasive pattern, diagnosis with stool patterns
288
What are features that can distinguish yersinia enterocolitica from Crohn's, and from appendicitis?
From crohns - acute onset
From appendicitis - diarrhea
289
What are major causes of enterotoxic diarrhea?
Vibrio cholerae, enterotoxic e coli
Never invasive - watery stool, often voluminous, often dehydrating
Caused by infected water or food
Organisms adhere to enterocytes, followed by elaboration of a toxin
290
How does vibrio cholerae cause waterry diarrhea?
A and B subunits of enterotoxin
B unit Binds enterocytes - in small bowel
A unit Activates intracellular Adenylate cyclase, which stimulates secretion
Colon not involved
291
What is enterotoxigenic e coli?
Most common cause of travelers diarrhea
Non-invasive
2 toxins - heat labile - resembels cholera toxin A (actiavtes Adenylate cyclase)
heat stable - activates guanylate cyclase
292
What is enterotoxigenic e coli O1:H157
May be epidemic
Adheres to distal small bowel
Shiga-like toxin causes mucosal destruction, allowing toxin to enter circulation and bind to blood cells
Causes hemolytic uremic syndrome (HUS)
293
How does staph aureus produce GI symptoms?
Preformed toxin - usually in dairy or cream products
Inadequate heating ot kill spores
Typical presentation is very early onset of upper GI symptoms (1-4 hours)
Followed by diarrhea - whole episode resolves in 24 hours
294
What is the pathogenesis of clostridium perfingens?
May be epidemic
Almost always inadequately heated meat
Spores survive and organism proliferates rapidly, if not adquately cooled immediately
Diarrhea starts about 8-24 hours after ingestion, self limited after about 24 hours
295
What is the most common source of traveler's diarhea?
Enterotoxigenic e coli
296
What is the most common type of community acquired gastroenteritis
Viral
297
What is the most common cause of diarrhea in young children?
Viral
298
What is the main culprit of viral gastroenteritis?
Rotavirus - double stranded RNA virus
Proliferation of secretory crypt cells - secretory diarrhea
Destruciton of mature enterocytes in small bowel
BBM enzymes reduced - undigested disaccharides - osmotic component
Fecal-oral, respiratory secretions, contaminated surfaces
299
What is the most common cause of community acquired infectious diarrhea in adults?
Norovirus - norwalk virus
300
What is significant about hte pathogenicity of norovirus?
Need very small inoculum
Non-invasive
Reversible lesions in upper jejunum - loss of BBM enzynems - can lead ot osmotic diarrhea
Abrupt onset - lasts 12-60 hours
301
What are risk factors for C. diff?
Typically after exposure to antibiotics, or nosocomial exposure
Highest risk is **clindamycin**
Most commonly used in patients treated with penicillins, cephalosporins, and early generation quinolones
INcreased risk with age and PPI use
302
What antibiotic has the highest risk of c. diff?
Clindamycin
303
How does c. diff cause disease?
part of normal flora - becomes pathogenic when normal flora disturbed
304
What are presentations of c. diff?
Asymptomatic, diarrhea, pseudomembranous colitis, severe fulminant oclitis,
(Broad spectrum)
305
What do we see here?
Pseudomembranes from C. diff colitis
Volcanic eruptions
306
What is giardiasis?
More common in IgA deficient patients
Watery diarrhea
More likely to produce upper GI symptoms
307
What infeciton is common in patients with IgA deficiency?
Giardiasis
308
What are differences between IBD and IBS?
309
What are causes of colitis?
Ulcerative colitis
Crohns
Radiation, ischemia, infection, antibiotics, NSAIDS, diversion colitis, diverticular colitis
310
How do you differentiate between acute infection and IBD?
Duration of symptoms, onset of symptoms, platelets, Hgb and biopsy
311
Where is the inflammation in ulcerative colitis?
Only in colon - Mucosal only
Pan colitis
312
Where is the inflammation in crohn's disease?
Transmural inflammation that can be in the proximal colon (ileitis, ileocolitis, colitis)
313
What are environmental risk factors for IBD?
Smoking, appendectomy, high sanitation level in childhood, high intake of refined carbohydrates, perinatal infection
314
What is the role of bacteria in the pathogenesis of IBD?
Germ free models do not develop colitis
315
Which IBD affects rectum?
UC - Starts at rectum, and works its way back. May have abrupt cutoff. Continuous
CD - patchy, transmural inflammation at any part of GI tract
316
What are features of UC?
Colon only
Mucousal inflammation
Continuous distribution
Rectal involvement
317
What are potential extents of UC?
318
What are we looking at?
Spectrum of disease - UC
319
What are complications of ulcerative colitis?
Toxic colitis - megacolon
Dilatation of large bowel - gas
Prelude to perforation
320
What are features of Crohns Disease?
Transmural, patchy inflammation
Can affect any part of the GI tract
321
Where is Crohn's Disease commonly presenting?
322
What does Crohn's Disease look like on the gut wall?
Transmural inflammation
323
What is this?
Aphthae - how inflammation begins in Crohn's Disease
324
What are complications of Crohn's Disease?
Inflammation, Fistulization, Obstruction, Microperforation
325
This is an ileum, what is this?
Crohn's Ileitis - Cobblestone ulceration
326
What do we see here?
Cobblestoning, Cookie cutter ulcers, deep ulcers
Crohn's Disease
327
What is this?
Cobblestone appearance of Crohn's Disease
328
What is this? When does it occur?
Granuloma - Hallmark of Crohn's Disease, but only seen in \< 30% of pts
329
What is a hallmark of Crohn's that differentiates from Ulcerative colitis, that surgeons often see?
Creeping mesenteric fat
330
What are symptoms of strictures/obstructions that are often seen as complications of Crohn's Disease?
Post-prandial cramps
Distention
Borborygmi - loud bowel sounds
Vomiting
Weight loss
331
Where can fistulas occur in Crohn's Disease?
Enteroenteric - can be asymptomatic
Enterovesical - can present as UTIs
Retroperitoneal - abscess signs, if affets psoas
Enterocutaneous - drainage via scar
Perianal - pain, drainage
Rectovaginal - drainage
332
What are the most common fistulas seen in crohn's disease?
Perianal
333
Which IBD classically involves the rectum?
UC
CD doesn't typically
334
What are some extra-GI features of IBD (Both UC and CD)?
Aphthous stomatitis, episcleritis and uveitis, arthritis, vascular, E. nodosum, p. gangrenosum
335
How does the arthritis of IBD typically present?
Monoarticular, asymmetrical, large joints, no synovial destruction, seronegative
336
What are long term copmlications of IBD?
Neoplasms - UC and CD: colorectal cancer; CD: small bowel adenocarcinoma
Nutritional and metabolic distrubances
337
What are long term sequellae of IBD?
Gallstones, malabsorption, renal disease
338
How do children with IBD present?
Fever
Anemia
Arthritis
Failure of growth and development
339
How do you treat IBD?
Anti-inflammatory (5-aminosalicylates, corticosteroids)
Immunomodulators (azathioprine, 6-mercaptopurine, MTX)
Biologics (infliximab, adalimumab, certolizumab, golimumab)
Antibiotics (Crohn's more than UC)
Surgical therapy
340
What surgery is used for UC vs Crohn's?
UC = total proctocolectomy with end-ileostomy
Crohn's - Segmental resection with primary anastamosis
341
When you have collar-button ulcers, what are you thinking?
Entameoba hystolitica
342
What antibiotic can be used to increase gastric emptying?
Erythromycin - motilin receptor agonist
343
What is the activity of metoclopramide?
Dopamine receptor antagonist, seratonin receptor agonist
Prokinetic
344
What is domperidone?
D2- receptor antagonist (peripheral)
Not available in US - prokinetic therapy
345
How does Nausea and Vomiting occur physiologically?
346
What are classes of anti-emetics?
Central muscarinics, Dopaminergic (D2), histaminergic (H1), serotinergic (5-HT3)
347
What are phentothiazines?
D2 receptor blockers in the CTZ that are anti-emetics
Also have anithistamine and anticholinergic effects
Adverse = parkinson-like symptoms
E.g. prochlorperazine, chlorpromazine
348
What are the buytrophenones?
Haloperidol, droperidol
Dopaminergic receptor inhibitors
Used for anti-emesis
Toxicity = parkinson-like effects
349
What are the 5-HT3 antagonist anti-emetics?
the -setrons (ondansetron, tropisetron, granisetron)
Acts at 5-HT3 receptor in CTZ
Mild gastric prokinetic effects
350
What are anti-diarrheals?
Anti-motility agents used in clinical conditions of reduced absorptive surface, or diarrhea of other etiology
E.g. loperamide, diphenoxylate with atropine, codeine, opium drops
351
What is octreotide?
Synthetic analogue of somatostatin - used in inhibiting release of secretory hormones in secretory tumors
Gastrinomas, carcinoid tumors, VIPomas
352
What is clonidine used for in GI?
Adrenergic stimulation increases electrolyte absorption and inhibits fluid secretion
Use limited by hypotension, drowsiness and depression
353
What cells typically release 5-HT in the motility pathway?
enterochromaffin cells
354
What is alosetron?
5-HT3 receptor antagonist used in treatment of IBS-Diarrhea
Block serotonin efect on myenteric plexus acetylcholine release, leads to reduced chloride secretion and decreased motility
355
What do you want to do to treat a constipated patient?
Increase secretion - chloride transport is curcial in regulation of fluid secretion
Activation of apical chloride channels and arriers leads to secretion of Cl ions which is the major determinant of mucosal hydration throughout GI tract
356
What is lubiprostone?
Chloride-induced secretion stimulatnt
Prostaglandin derivative that is highly selective to type 2 Cl channel
Exerts secratoggue effects through activation of CFTR to increase Cl secretion
357
What is linactolide?
Agonist of guanylate cyclase C receptors on luminal surface of intestinal goblet and enteroendocrine cells
INcreases intracellular cGMP leading to activation fo CFTR
358
37 year old successful stock broker, entertains clients 4 nights weekly for last 6 years. Typically drinks about 5 mixed drinks each dinner. Develops 5 BMs/day, greasy and particularly foul smelling.
Treat with?
Presentation consistent with chronic alcoholism and pancreatic insufficiency: Treat with pancreatic enzymes
359
27 year old NYC diamond dealer with 6 year history of ileitis undergoes resection of 35 cm of terminal ileum .Within 2 weeks of surgery develops 6 loose BMs daily
Pt has had resection of site of bile salt reabsorption and bile salts are spilling into colon causing an irritant effect leading to watery diarrhea. Treatment: use cholestyramine or other bile salt binding agent
360
59 year old develops epigastric pain. Self treats himself with OTC omeprazole for 8 weeks without success. Endoscopy reveals 2 large gastric ulcers and multiple ulcers in duodenal bulb. He develops 8 watery bowel movements daily that do not diminish with decrease in fasting.
Symptoms are consistent with gastrinoma and a secretory diarrhea, ie. gastrinoma. Treatment: Attempt location of tumor for resection if possible, and use octreotide to reduce the gastrin- stimulated diarrhea.
361
66 year old woman has just had a colectomy for Crohn’s disease and has had 3 prior small bowel (SB) resections. She has 160 cm of residual SB. She has over 2 liters of ileostomy output daily.
She has lost her colonic water absorptive capacity. Her length of residual small bowel is adequate to avoid malabsorption as a cause of her diarrhea. Treatment: Use agents to slow intestinal motility to increase absorbtive time (e.g. loperamide, diphenoylate, codeine)
362
19 year old college freshman half marathon state champion, drinks approximately 3 liters of caffeine-free diet soda daily, often before long training runs. She has 6 watery BMs daily with near incontinence during long training runs.
In her diet soda she is ingesting large amounts of non-absorbed osmotic artificial sweeteners e.g. sorbitol
363
61 year old ER nurse, develops diarrhea consisting of up to 8 watery BMs daily. She has developed flushing that reminds her of her months of emerging menopause 8 years ago.
Combination of watery diarrhea in combination with flushing should suggest the diagnosis of carcinoid tumor. As with gastrinoma, described above, surgical management is the primary option and octreotide is used to reduce the secretory diarrhea
364
71yearold,livinginanursinghomeisfebrile to 101.0F is admitted to the hospital for treatment of pneumonia with amoxacillin-clavulinic acid. 3 days after admission she develops 8 watery BMs daily and spikes a fever to 102.9F.
New onset of diarrhea in the hospital, especially with antibiotic use strongly suggests the diagnosis of Clostridium difficile. Treatment: Metronidazole or vancomycin and try to limit antibiotic use.
365
A 29 year old is addicted to oxycontin and is admitted for in-patient detoxification. He develops, nausea, vomiting, and 8 watery BMs/day during the first 48 hours of narcotic withdrawal.
Symptoms are consistent with narcotic withdrawal syndrome. This form of diarrhea is treated with clonidine. Use is often limited by hypotension.
366
What do we see here?
Normal colon
367
What do you see here?
Ulcerative colitis - we know because:
- Affects colon and rectum only
- Continuous inflammaiton
- Retrograde spread from rectum
- partial or pancolitis
- Circumferential inflammation
368
What do we see here?
Ulcerative colitis - Mucosal inflammation only
369
Normal on left, what is on right?
Distorted crypts, dense mononuclear inflammatory cells
UC or Crohn's
370
Why do IBD have deformities of crypts?
Destruction and reconstruction, allows deformation to occur
371
What do we see here?
Crohn's disease, we can tell because:
- Any part of Gi tract
- Thickened bowel wall
- Stenosis
- Discontinuous
- Cobblestoning andulcers
- Non-circumferential
372
What do we see here?
Thick mesentery, creeping fat
Crohn's Disease
373
What is significant about hte inflammation seen in Crohn's disease vs in UC?
Transmural!
374
What do we see here?
Transmural inflammation seen in Crohn's Disease
375
What is a pathological feature of Crohn's Disease that can clinch a diagnosis?
Granulomas
376
What feature of Crohn's Disease is this?
Granulomas
377
What is a potential complication of crohn's disease shown here?
Penetrating fissures, leading to peritonitis
378
When can this occur?
Severely active Ulcerative Colitis or Crohns Disease
379
What do we see here?
Atrophic mucosa after long IBD course ("burned out IBD")
Everything becomes flat and featureless
380
What do we see here?
Inflammatory polyps
Can indicate UC or CD
381
What sequellae of IBD is characterized by massive dilation and potentially perforation of the colon?
Toxic Megacolon
382
Where does toxic megacolon typically present?
Transverse colon
383
What is a dangerous risk of IBD?
Dysplasia and then cancer
384
C. diff- associated colitis
385
What do we see here?
Pseudomembranous colitis
Likely Clostridium difficile-associated colitis
386
What do we see here?
Pseudomembranes
Surface necrosis, dilated crypts, volcano like acute inflammatory exudates
Likely from C. Difficile Colitis
387
What is clostridium difficile?
Gram positive, spore-forming rod
Endemic in healthcare settings
Easy transmission
Altered colonic microlfora due to broad spectum antibiotics and chemo
Treat with metronidazole, vancomycin, fecal transplant
388
Colonic ischemia
389
What factors can predispose a patient to colonic ischemia?
Low blodo flow relative to tissue mass
Poor collaterals
Watershed regions (SMA-IMA, IMA-hypogastric
Sensitivity to vasoconstrictors
Long vasa recta
Reduced blood flow during mechanical activity
Countercurrent blood flow
390
What are the watershed areas of blood flow of the colon?
391
What is the significance of countercurrent blood flow in the colon?
Can cause colonic ischemia - veins can draw oxygen from arteries in colon
392
Who gets colonic ischemia?
Elderly patients (heart dx, vascular dx, low-flow states)
Shock
Young patients (heavy exercise, oral contraceptives, vasoconstrictive drugs, usually limited to mucosa and resolves completely)
393
What do we see here?
Colonic ischemia
394
What occurs in colonic ischemia?
Edema of colon - engorged blood vessels followed by leakage of plasma and rbcs into tissue
395
Which disease has characteristic "thumbprinting" in the colon on barium enema?
Colonic ischemia
396
What is this?
Diverticular disease
397
What do we see here?
Diverticular disease
398
What are presentations of diverticular disease?
Painless bleeding
Inflammation (diverticulitis) - can cause perforation and peritonitis
Fever, LLQ tenderness, rope-like mass
399
Can be collagenous colitis - need biopsy to know
400
What do we see here?
Collagenous colitis
401
What do we see here?
Lymphocytic colitis
402
What are differences between collagneous and lymphocytic colitis
Both have chronic watery diarrhea, grossly normal mucosa, microscopic chronic inflammation
403
What geographic regions get colon cancer?
Well-developed countries
404
What are the strongest risk factors for developing colon cancer?
Advancing age (\>50)
Country of birth
Hereditary syndrome (FAP, Lynch)
Longstanding IBD
405
What are the strongest protective factors for colon cancer?
Physical activity
Aspirin, NSAIDs
**Colonoscopy**
406
How does colon cancer develop?
Normal -\> Adenomatous polyp -\> cancer
During 5-10 years
407
What defines stage III colon cancer?
spread to lymph nodes
408
What defines stage IV colon cancer?
Spread to other organs
409
What defines stage II colon cancer?
Breach of mucosal layers
410
What determines prognosis of colon cancer?
staging
411
What do patients present with when they have colon cancer?
Constipation/difficulty passing stool, bleeding, GI pain/discomfort
Desmoplastic reaction can casue narrowing of lumen
412
What is this?
Pedunculated tubular adenoma
413
What defines invasive vs non-invasive cancer in colon cancer?
If it passes through the muscularis mucosa
414
What is this?
Sessile serrated polyp
415
What are the molecular pathways of colon carcinogenesis?
APC, then k-ras, then DCC/18q genes, then p53
416
What is microsatelite instability?
Mutation/loss of DNA mismatch repair genes
Mutations of key target genes (TGFβRII)
e.g. Lynch Syndrome
417
What is CpG Island Methylation (CIMP)?
DNA methylation inhibits key gene expression
BRAF oncogene mutation
Mechanism of sessile serrated polyp leading to cancer
418
What are common symptoms of colon cancer?
NO SYMPTOMS
Change in nature of stool (color - red/black/tar; caliber - thinner; frequency - less often, more often)
Abdominal discomfort or cramps
Unexplained weight loss
Loss of apetite
Anemia
419
What are hte most common signs of colon cancer?
Abdominal mass, tenderness, distention
Enlarged liver (if metastatic)
Abnormal rectal exam - mass, fecal occut blood test positive
May not have signs
420
What symptoms occur when a patient has a cancer on their right side of the colon?
Occult bleedign, anemia
Left - obstructive symptoms, overt bleedign
421
What symptoms occur when a patient has a colon cancer on their left side of the colon?
Obstructive symptoms, overt bleeding
Right - occult bleedign, anemia
422
Who is at average risk of colon cancer?
Men + women older than 50 years old
423
What are high risk colon cancer groups?
Hereditary syndromes
IBD
Family history
Personal history
424
What is the gold standard of colon cancer screening?
Colonoscopy
425
What is a radiographic technique that can be used for screening for colon cancer?
Barium enema - can see the "apple core" lesion
426
How do you change colon cancer surveillance for patients with family histories?
Start screening 10 years earlier
427
What is the lifetime risk of cancer in FAP?
100%
428
What is this?
FAP
429
What is the genetics of FAP?
Autosomal dominant inherited syndrome
430
Where can lesions occur in FAP?
Anywhere in GI tract
431
What gene is mutated in FAP?
APC gene
432
Do you need a family history to have FAP?
No - up to 30% are de novo mutations
433
What is lynch syndrome?
(hereditary non-polyposis colon cancer)
Autosomal dominant Germline mutations in DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2, MSH6)
434
What are genetic features of colon cancers from lynch syndrome?
Microsatellite instability
435
What are clinical features of lynch syndrome?
Colonic neoplasms (few adenomas, proximal locaiton, multiple simultaneous cancers, typical histology - signet ring cell, mucinous)
Extraintestinal cancers (endometrium, GU, Small bowel, Brain, Stomach, OVary, pancreas)
436
What test do you do on colon cancers that would be positive in Lynch syndrome?
MSI - microsatellite instability
Done on tissue, not blood
95% of lynch syndrome tumors are MSI+, 10-15% of sporadics are MSI+
437
How do you know if a patient ahs lynch syndrome?
Family history
3,2, 1 rule
3 or more HNPCC-associated cancers - two of whom are first-degree relatives
2 or more generations
1 person affected before age 50
438
What is this?
Colorectal adenoma
Most common polyp wherever colorectal cancer is common
Usually after 40 years old
Anywehre in colon or rectum
1/2-2 cm in size, but can be smaller or larger
Benign, but potential origin of cancer
439
How does one define a colorectal adenoma?
benign neoplasm containing dysplastic colorectal epithelium
440
What do we see here?
Colorectal adenoma - benign neoplasm consisting of dysplastic colorectal epithelium
441
What are differences between dysplastic colorectal epithelium and normal epithelium?
Nuclei are elongated, darkly stained, crowded, overlapping
Cytoplasm is blurred distinction between enterocytes and goblet cells, reduced or excessive mucin
442
What is tubular adenoma vs villous adenoma?
Tubular - tubules in adenoma
Villous - Finger-like prongs
Distinction made on lower magnification
443
What do we see here? howd o you know?
Pedunculated tubular adenoma
- smooth gross appearance is characteristic of tubular adenomas
444
What do you see here?
Villous adenoma
Typically presenting as large and sessile (not pedunculated)
445
What do you see here?
villous adenoma
They are rarely huge and carpet-like
May cause watery diarrhea, hypokalemia
446
What is a difference between the sizes of villous and tubular adenomas?
Villous can be very very large - can cause watery diarrhea, hypokalemia
447
What is a hyperplastic polyp?
Tiny (\<1cm)
Clinically insignificant
Hard to distinguish from adenoma, similar to adenomas in age adn geographic distribution and may harbor genetic mutations
Taken out anyways (because you can't really tell)
448
What are these?
Hyperpastic polyps
Elongated, serrated, not dysplastic
449
What is a sessile serrated polyp?
Precuror of microsatellite unstable CRC
Can be seen with narrow band imaging
450
What are differences between hyperplastic polyps and sessile serrated polyps?
451
What do we see here?
 
Adenoma glands
Organized, tubular or villous shapes, no stromal reaction
452
What do we see here?
 
Cancer glands
Disorganized
Sharp angulations
Desmoplastic stroma
453
What is the most important prognostic indicator of colorectal cancer?
Tumor stage
454
What parameters are used in tumor staging?
Depth of tumor invasion
Lymph node metastases
455
What are prognostic indicators of CRC that arent involved in staging?
Completeness of resection
Histologic grade (differention)
Venous invasion
Distribution of nodal mets
Molecular features
456
What about differentiation of colorectal cancers is a prognostic feature?
Poor differentiatino - worse
457
Which of htese colon cancers is owrse?
On the right - worse
458
Is mucinous adenocarcinoma an important prognostic feature?
NO
459
What features do MSI cancers often have that can be identified histologically via immunostain?
Lymphocyte infiltration (CD3 immunostain)
This is a favorable prognostic finding
460
What is a common, small appendiceal tumor that occurs in the tip and is rarely malignant?
Appendiceal carcinoid
461
This is in the appendix, what is htis?
Appendiceal carcinoid - nesting tumor pattern, round nuclei, speckled chromatin
462
When you see evenly spaced, round nuclei in a histologic section of the appendix, what are you thinking?
Appendiceal carcinoid
463
What is a mucinous cystadenoma?
Benign tumor of the appendix\