Block 7 (GI) - L16 to L19 Flashcards
1
Q
What systems are required for digestion and absorption?
A
- Mechanical (chewing, trituration, peristalsis)
- Enzymatic/chemical (amylase, HCl, pepsin, lactase)
- Hormonal (CCK, peptide YY)
- Structural (villi, intestinal length, IC valve)
- Transport proteins and barrier functions (GLUT, desmosomes)
- Microbiome (vitamin K, fermentation)
- Lymphatic (chyle transport)
- Vascular (nutrient transport, tissue oxygenation)
- Metabolic (mitochondria, glycogen storage/glycolysis)
- Neurologic (control center)
- Electric (gastric pacemaker waves)
2
Q
Absence of brush border enzymes causes what common malabsorption disorder?
A
Lactose intolerance
3
Q
What can cause temporary lactose intolerance?
A
Infection
4
Q
What is useful in short gut syndrome and fat malabsorptive disorders and why?
A
Medium chain triglycerides (directly absorbed across the mucosa into the portal vein - no bile salts, lipase, colipase, or ileum required)
5
Q
What are the limitations of MCT oil?
A
- Doesn’t contain essential fatty acids (can cause EFA deficiency)
- Excess is metabolized to ketones (can cause metabolic acidosis)
6
Q
What is primarily absorbed in the duodenum?
A
Calcium, iron
7
Q
What is primarily absorbed in the jejunum?
A
Monosaccharides, water soluble vitamins, electrolytes, trace minerals, fat, fat soluble vitamins, protein, water, alcohol, magneisum
8
Q
What is primarily absorbed in the ileum?
A
Vitamin B12 and bile salts
9
Q
What is primarily absorbed in the colon?
A
Water, electrolytes, SCFAs
10
Q
List the components of bile. How much is secreted daily?
A
- Bile acids (cholic, chenodeoxycholic, deoxycholic, lithocholic)
- Phospholipids (lecithin)
- Cholesterol
- Pigments (bilirubin)
- Inorganic ions
250mL-1L
11
Q
List the components of pancreatic secretions. How much is secreted daily?
A
- Aqueous component: bicarbonate - neutralizes acid and activates enzymes
- Enzymatic component: amylase, lipase, protease
12
Q
Where is iron, B1, and folate absorbed?
A
Duodenum
13
Q
What are clinical signs of malabsorption?
A
- Diarrhea
- Steatorrhea
- Bloating
- Weight loss
- Dehydration
- Growth retardation/failure to thrive
- Edema
- Anemia/bleeding tendencies
- Muscle cramping
- Bone deterioration
14
Q
Watery diarrhea indicates ___ malabsorption.
A
Carbohydrate
15
Q
Anemia/bleeding tendencies indicates possible malabsorption of what 4 things?
A
B12, iron, folate, vitamin K
16
Q
Muscle cramping indicates possible malabsorption of what 4 things?
A
Ca2+, Mg2+, phosphorus, vitamin D
17
Q
Bone deterioration indicates possible malabsorption of what 2 things?
A
Vitamin D, calcium
18
Q
List 7 classic malabsorptive disorders.
A
- Celiac disease
- CF
- Chronic pancreatitis
- Lactose intolerance
- bacterial overgrowth
- Whipple’s disease
- Tropical sprue
19
Q
What is celiac disease?
A
Multifactorial autoimmune disorder in genetically susceptible individuals
20
Q
What triggers celiac disease?
A
The protein gluten, found in wheat, and proteins in rye and barley
21
Q
Describe the pathogenesis of celiac disease.
A
Infiltration of the SI by lymphocytes attacking TTG causes an inflammatory reaction leading to flattening of the SI mucosa
22
Q
What is the genetic mutation associated with celiac disease?
A
HLA DQ2/8
23
Q
Malabsorption of what things is common in celiac disease?
A
Iron, folate, calcium, vitamin D (B12 is rare)
24
Q
How is celiac disease screened and confirmed?
A
Screen with serum TTG Ab test
Confirmed with small bowel biopsy
25
What can hypoalbuminemia and/or anemia indicate RE malabsorption?
Folate or B12 deficiency (macroscopic anemia)
Iron deficiency (microscopic anemia)
26
What is the most important test for suspected malabsorption?
Sudan stain of fecal fat
27
What does a lactose hydrogen breath test indicate?
If hydrogen is elevated >20ppm in response to lactose ingestion (?)
28
Fecal elastase is low in ___.
Pancreatic insufficiency
29
Stool pH is low in ___.
Carbohydrate malabsorption
30
What is D-xylose test used for?
Differentiates malabsorption secondary to mucosal damage from malabsorption due to pancreatic sufficiency/other
31
What is seen on microscopic examination in Whipple's disease?
Foamy macrophages, positive PAS stain
32
What are three broad categories of hepatic circulatory disorders?
1. Hepatic vein outflow obstruction
2. Impaired intrahepatic blood flow
3. Impaired blood inflow
33
What are causes of hepatic vein outflow obstruction?
1. Hepatic vein thrombosis (Budd-Chiari syndrome)
| 2. Veno-occlusive disease
34
What are causes of impaired intrahepatic blood flow?
1. Cirrhosis
2. Sinusoid occlusion
3. Systemic circulatory compromise
35
What are causes of impaired blood inflow?
1. Hepatic artery compromise
2. Portal vein obstruction
3. Intra- or extra-hepatic thrombosis
36
How does hepatic vein outflow obstruction manifest?
Ascites, hepatomegaly, abdominal pain, elevated transaminases, jaundice
37
How does impaired intrahepatic blood flow manifest?
Ascites (cirrhosis), esophageal varices (cirrhosis), hepatomegaly, elevated transaminases
38
How does impaired blood inflow manifest?
Esophageal varices, splenomegaly, intestinal congestion
39
What is Budd-Chiari Syndrome and what are its symptoms?
Hepatic vein obstruction/thrombosis
Hepatomegaly, ascites, abdominal pain, hepatic dysfunction
40
What are some etiologies of Budd-Chiari Syndrome?
1. Primary myeloproliferative disorders
2. Inherited disorders of coagulation
3. Antiphospholipid syndrome
4. Paroxysmal nocturnal hemoglobinuria
5. Intra-abdominal cancers
6. Oral contraceptives
7. Pregnancy
41
What is seen histologically in Budd-Chiari syndrome?
Centrilobular congestion
42
What is sinusoidal obstruction syndrome?
Hepatic venous outflow impairment is due to occlusion of the terminal hepatic venules and hepatic sinusoids
43
Who is at risk for sinusoidal obstruction syndrome?
Bone marrow transplant patients (highest risk in first 3 weeks), chemotherapy patients, drugs (such as azathioprine)
44
What is the pathogenesis of sinusoidal obstructive syndrome?
Toxic injury to the sinusoidal endothelium with resulting fibrotic occlusion of small hepatic veins
45
What are the symptoms of sinusoidal obstructive syndrome?
1. Acute RUQ tenderness
2. Hepatomegaly
3. Ascites
4. Weight gain
5. Jaundice
46
What is seen on histology in sinusoidal obstruction syndrome?
Fibrous obliteration of the central vein
47
What is acute fatty liver of pregnancy?
Sudden catastrophic illness occurring exclusively in the 3rd trimester characterized by microvesicular fatty infiltration that can lead to acute liver failure and encephalopathy
48
What is seen histologically in acute fatty liver disease of pregnancy?
Microvesicular steatosis (fat in the hepatocyte does not push the nucleus to the side)
49
What is the most common non-malignant tumor of the liver?
Focal nodular hyperplasia (FNH)
50
What causes FNH?
Localized overgrowth of hepatocytes
51
What are the two major features of FNH?
1. Solitary
| 2. Central stellate scar
52
What age group is affected by FNH?
20-40 year olds
53
What is the malignant potential of FNH and what is the treatment?
No malignant potential
| No treatment necessary
54
What is nodular regenerative hyperplasia?
Transformation of the hepatic parenchyma into small regenerative nodules in the absence of fibrosis
55
What can nodular regenerative hyperplasia cause?
Non-cirrhotic portal hypertension
56
What are conditions associated with nodular regenerative hyperplasia?
1. Solid organ and bone marrow transplant
| 2. HIV
57
What is a hepatic adenoma?
Benign tumor of the liver
58
Hepatic adenomas are common in ___ and are associated with what two things?
Young women; pregnancy and oral contraceptive use
59
What is seen on histology in a hepatic adenoma?
Sheets and cords of normal hepatocytes with ABSENT portal tracts and prominent solitary arterial vessels
60
Does hepatic adenoma have a risk of transforming into hepatocellular caricinoma?
Yes, though it is rare
61
What is a hemangioma?
Most common benign tumor of the liver
62
What is seen histologically in hemangioma?
Benign vascular channels and fibrous tissue
63
What is the most common primary malignant liver tumor of childhood?
Hepatoblastoma
64
Hepatoblastoma affects ___ > ___.
M>F
65
What is seen on physical exam and labs in hepatoblastoma?
RUQ mass
Elevated alpha fetoprotein
66
95% of ___ cases occur in patients with cirrhosis. What is the exception to this rule?
Hepatocellular carcinoma; can occur independent of cirrhosis in hepatitis B
67
What are causes of hepatocellular carcinoma?
1. Cirrhosis of any cause (NASH, alcohol, hepatitis C, hemochromatosis)
2. Chronic hepatiti B
3. NASH
4. Food contaminants (Aflatoxin - Africa)
5. Hereditary Tyrosinemia
68
What is the pathogenesis of hepatocellular carcinoma?
Accumulation of mutations because of repeated cycles of cell death and regeneration
Also, integration of viral DNA in HBV
69
Describe the clinical presentation of HCC.
Vague symptoms
50% have elevated alpha fetoprotein
Detected on imaging studies
70
What is the fibrolamellar varient of HCC?
Rare variant the occurs in younger women and is characterized by areas of dense collagenous fibrosis and large polygonal tumor cells (better prognosis); not associated with liver disease
71
What is a cholangiocarcinoma?
Malignancy of the bile ducts (within or outside the liver)
72
10% of cholangiocarinoma are intrahepatic and arise from bile ducts within the liver. The rest are extra-hepatic. Where do these occur?
1. Perihilar (50-60%)
2. Distal bile duct (20-30%)
3. Periampullary
73
What are risk factors for cholangiocarcinoma?
1. Primary sclerosing cholangitis
2. Congenital fibropolycystic disease of the bilairy system (Caroli's disease)
3. Cirrhosis
4. Exposure to Thorotrast
5. Opisthochis sinensis (liver fluke)
74
What are the gross and clinical findings of intra-hepatic cholangiocarcinoma?
Not detected until late; massive lesion or tree-like tumor tracking along the portal system; often presents as biliary obstruction or a symptomatic mass
75
What are the gross and clinical findings of extra-hepatic cholangiocarcinoma?
Small lesions at the time of diagnosis, biliary obstruction + jaundice, cholangitis, RUQ pain
76
Intra-hepatic cholangiocarcinoma is a ___ (type), with ___ on histology, and sometimes combines with ___.
Adenocarcinoma; dense fibrous stroma; HCC
77
What is a Klatskin tumor?
Special varian of extra-hepatic cholangiocarcinoma occurring at the hilum
78
What are common causes of metastatic cancer in the liver in adults?
Breast, lung, colon, pancreas
79
What are common causes of metastatic cancer in the liver in children?
Neuroblastoma, Wilms tumor, rhabdomyosarcoma
80
Hepatocytes excrete bile into the ___, which flows ___ the central vein.
Canaliculus; away from
81
Describe the path from the bile canaliculus to the common bile duct.
1. Bile canaliculus
2. Terminal ductules
3. Interlobular bile ducts
4. L/R hepatic duct
5. Common hepatic duct
6. Cystic duct (empties into gall bladder)
7. Common bile duct
82
What are bile acids used for?
Digestion and absorption of fats and fat-soluble vitamins in the SI
83
Many waste products, including ___, are eliminated from the body by secretion into bile and elimination in feces.
Bilirubin
84
Bile acids are derivatives of ___ synthesized in the ___.
Cholesterol; hepatocyte
85
What are the two main bile acids?
Cholic and chenodeoxycholic acid
86
Describe the process of production and elimination of bilirubin.
1. RBC taken up by phagocyte and broken down into heme, globin, and iron
2. Heme is converted to biliverdin and then to bilirubin
3. Bilirubin is transported via albumin to the hepatocytes
4. Free bilirubin is conjugated to glucuronic acid to form conjugated bilirubin and secreted into the bile canaliculus and delivered to the SI
5. Bacteria metabolize bilirubin to be eliminated in feces or in urine (after reabsorption)
87
How much bilirubin is produced each day?
4 mgl/dL
88
Which form of bilirubin is excreted into aqueous bile and which remains in the blood?
Conjugated; unconjugated
89
What is jaundice?
Yellow pigmentation of the skin/sclera/mucus membranes produced by increased serum bilirubin
90
What are the two types of hyperbilirubinemia and how are they different?
Unconjugated (water insoluble) and conjugated (water soluble)
91
When is evaluation of jaundice emergent?
1. Massive hemolysis
2. Ascending cholangitis
3. Unconjugated hyperbilirubinemia in a neonate
4. Acute liver failure
92
What aspects of the clinical history are important in a patient with jaundice?
1. Medications (including drugs/herbs)
2. Alcohol
3. Hepatitis risk factors
4. History of abdominal operations/gallbladder surgery
5. History of inherited disorders (liver/hemolytic)
6. HIV status
7. Travel history
8. Toxic substance exposure
9. Fevers, anorexia, myalgias, malaise
93
What are important PE signs to look for in a patient with jaundice?
1. Courvoisier sign (palpable gallbladder)
2. Signs of portal HTN or chronic liver disease (ascites, splenomegaly, spider angiomata, gynecomastia, skin hyperpigmentation = hemochromatosis, Kayser-Fleischer rings = Wilson's, xanthomas = primary biliary cirrhosis)
94
What initial lab screenings should be done?
Determine if jaundice is hepatocellular or obstructive:
```
Measure total bilirubin and indirect fraction
Serum transaminases
Alkaline phosphatase
PT/INR
Serum albumin
Platelet count
```
95
If you suspect a hepatocellular cause, what additional lab studies should be done?
1. Serologies for viral hepatitis
2. Anti-mitochondrial antibodies (PBC)
3. Anti-smooth muscle antibodies (autoimmune hepatitis)
4. Serum iron, transferrin, ferritin (hemochromatosis)
5. Serum ceruloplasmin/alpha-1-anti-trypsin levels
96
REVIEW SLIDE 21 - L19
Do it.
97
What is a common cause of unconjugated hyperbilirubinemia?
Gilbert's syndrome
98
What is Gilbert's syndrome?
Isolated elevation of total and indirect bilirubin in the presence of normal transaminases
99
What causes Gilbert's syndrome?
Genetic defect in the UDP-glucuronyl transferase
100
What is the epidemiology of Gilbert's syndrome?
7% of the population (M>F), present in 20's and 30's, exaggerated by fasting/viral illnesses
101
What are causes of intra-hepatic cholestatic jaundice and conjugated hyperbilirubinemia?
1. Drug-induced cholestasis
2. Primary biliary cirrhosis (PBC)
3. Sepsis
4. Post-operative jaundice
5. Primary hepatocellular disease
102
What should be done if you suspect obstruction of biliary tree?
Imaging studies - transabdominal ultrasound is screening of choice
103
What is bilirubinuria?
Conjugated bilirubin in the urine (will never see unconjugated bilirubin, which is tightly bound to albumin and not filtered by the glomerulus)
104
What is the most common cause of bilirubinuria?
Hepatocellular disease
105
What are rare causes of bilirubinuria?
Dubin-Johnson and Rotor syndrome (inability of hepatocytes to secrete conjugated bilirubin into the bile)
106
What is neonatal jaundice?
Yellowing of the skin in a newborn, bilirbuin > 5mg/dL
107
What is the most common cause of neonatal jaundice?
Breakdown of fetal Hgb as it is replaced with adult Hgb in a liver with immature metabolic pathways
108
What are uncommon causes of neonatal jaundice?
Biliary atresia, progressive familial intrahepatic cholestasis, Alagille syndrome, alpha-1 antitrypsin deficiency
109
What are diseases that affect the biliary tree?
Primary biliary cirrhosis
| Primary sclerosing cholangitis
110
What is primary biliary cirrhosis (PBC)?
A progressive cholestatic liver disease common in middle-aged women, causing destruction of intrahepatic bile ducts
111
What is the cause of PBC?
Autoimmune etiology
112
What lab tests indicate PBC?
Positive anti-mitochondrial antibody (AMA)
| Elevated Alk Phos (elevated total bilirubin is a sign of advanced disease)
113
What are the two most common initial symptoms of PBC?
Fatigue and pruritis (jaundice comes later)
114
What is a key histologic finding of PBC?
Florrid duct lesion - peridcutal inflammation with granuloma formation and duct destruction
115
What are the symptoms of primary biliary cirrhosis?
Pruritis, fatigue, xanthomas, jaundice
116
What is the treatment for PBC?
Ursodeoxycholic acid, then liver transplant
117
What is primary sclerosing cholangitis?
Obliterative fibrosis of intra- and extra-hepatic bile ducts with inflammation and dilation of preserved segments
118
What is seen on ERCP in primary sclerosing cholangitis?
Beading
119
What is PSC associated with?
IBD (ulcerative colitis and Crohn's disease)
120
What is seen on histology in PSC?
Onion skin pattern around bile ducts
121
What is choedocholithiasis?
Cholesterol stones in the bile duct
122
What is cholelithiasis?
Gallstones
123
How is diarrhea defined?
1. High stool frequency (>3/day)
2. >200g of stool/day
3. Abnormally loose stool
4. Not related to incontinence
124
How is acute diarrhea differentiated from chronic diarrhea?
Acute: <4 weeks
Chronic: >4 weeks
125
Acute diarrhea is self-limited and tends to resolve within ___.
1 week
126
What is a common cause of acute diarrhea?
Viral gastroenteritis or foodborne illness
127
How is acute diarrhea evaluated and managed?
1. Medication review
2. Supportive care
3. Further evaluation if diarrhea fails to resolve in 1 week
4. Can give antibiotics (ciprofloxacin and/or flagyl)
128
What are 5 groups at high risk for developing acute diarrhea?
1. Travelers
2. Consumers of certain foods
3. Immunodeficient persons
4. Daycare attendees and family members
5. People in hospitals
129
What organisms are common causes of acute diarrhea in travelers?
1. Campylobacter
2. Shigella
3. Aeromonas
4. Coronavirus
5. Salmonella
6. Norwalk virus (cruise ships)
7. Giardia (campers, hikers, swimmers)
130
What organisms are common causes of acute diarrhea in people who ate chicken?
1. Salmonella
2. Campylobacter
3. Shigella
131
What organisms are common causes of acute diarrhea in people who ate hamburgers?
1. E. coli (O157:H7)
132
What organisms are common causes of acute diarrhea in people who ate rice?
1. B. cereus
133
What organisms are common causes of acute diarrhea in people who ate eggs/mayo?
1. Salmonella
134
What organisms are common causes of acute diarrhea in people who ate seafood?
Vibrio
135
What organisms are common causes of acute diarrhea in people who have AIDS?
1. Mycobacterium
2. CMV, adenovirus, herpes
3. Cryptosporidium, Isospora
136
What organisms are common causes of acute diarrhea in people who attend daycare?
1. Shigella
2. Giardia
3. Cryptosporidium
4. Rotavirus
137
What organisms are common causes of acute diarrhea in people who are in the hospital?
1. C. dificile
138
What organisms are common causes of acute diarrhea within hours of ingestion of food (pre-formed toxins/enterotoxin producing organisms)?
1. B. cereus
2. Vibrio
3. ETEC
139
What organisms are common causes of acute, bloody diarrhea?
1. Entamoeba histolytica
140
Reiter's syndrome may cause acute diarrhea. What are the three symptoms of this syndrome and what organisms can cause it?
Arthritis, urethritis, conjunctivitis
Salmonella, Shigella, Campylobacter, Yersinia
141
What organisms are associated with HUS?
1. EHEC
| 2. Shigella
142
What are alarm signs in people who have acute diarrhea?
1. Severe abdominal pain
2. Fevers
3. Recent hospitalization or anti-microbial use
4. Special populations (elderly, immunocompromised, IBD, pregnancy)
143
What further evaluation can be done when acute diarrhea does not improve?
Stool culture, stool ova and parasite, stool leukocytes, endoscopy
144
What are the 5 types of diarrhea?
1. Steatorrhea
2. Secretory diarrhea
3. Osmotic diarrhea
4. Inflammatory diarrea
5. Motility-related diarrhea
145
Describe the stool seen in steatorrhea.
>14g/day of fat, bulky, oily, malodorous
May also have weight loss
146
What are causes of steatorrhea?
1. SIBO
2. Celiac disease
3. Whipple's disease
4. Pancreatic insufficiency
147
How is SIBO diagnosed?
Hydrogen breath test
148
What can cause secretory diarrhea?
1. Bile acid malabsorption
2. Medications (NSAIDs, colchicine)
3. Non-invasive infections (cholera)
4. Hormone producing tumors (VIPoma, metastatic carcinoid, etc.)
149
How can secretory diarrhea be distinguished from osmotic diarrhea?
Secretory diarrhea fails to improve with fasting and the stool osmotic gap <50
150
What causes osmotic diarrhea and what are some other symptoms?
Malabsorption of carbohydrates (lactose intolerance, laxatives)
Bloating and flatulence
151
How can osmotic diarrhea be distinguished from secretory diarrhea?
Osmotic diarrhea improves with fasting and the stool osmotic gap >100
152
What are some causes of inflammatory diarrhea?
IBD, ischemic colitis, radiation colitits
153
What are the symptoms associated with inflammatory diarrhea?
Abdominal pain, bleeding, fever, weight loss
154
What are some causes of motility-related diarrhea?
1. Hyperthyroidism
2. Diabetes
3. IBS
155
What are some causes of diarrhea in children?
1. Intussuscpetion
2. HUS
3. Pseudomembranous colitis
4. Appendicitis
5. Congenital secretory diarrhea
6. Antibiotic-associated diarrhea
156
How is constipation defined?
1. Straining during defecation
2. Passage of lumpy or hard stool
3. Sensation of incomplete defecation
4. Use of manual maneuvers to facilitate a bowel ovement
5. Frequency of less than 3 bowel movements per week
157
How is chronic constipation defined?
Symptoms > 3 months
158
What are some causes of recent onset constipation?
1. Colonic obstruction (neoplasm, stricture, ischemic, diverticular, inflammatory)
2. Anal sphincter spasm (anal fissure, painful hemorrhoids)
3. Medications
159
What are some causes of chronic constipation?
1. IBS
2. Medications (calcium channel blockers, antidepressants)
3. Colonic pseudoobstruction
4. Disorders of rectal evacuation
5. Endocrinopathies (hypothyroidism, hypercalcemia, pregnancy)
6. Psychiatric disorders (depression, eating disorders)
7. Neurologic disease (Parksinson, MS, spinal cord injury)
8. Progressive systemic sclerosis
160
How is constipation evaluated and managed?
1. H&P
2. Medication review
3. Labs
4. Evaluate for secondary causes
161
What are alarm signs related to constipation?
1. Age >50
2. New onset constipation in the elderly
3. Weight loss
4. Family history of colon cancer
5. History of abdominal or pelvic cancer
6. History of abdominal or pelvic radiation
7. History of colonic resection
8. Palpable mass on exam
162
What is a bulk-forming laxative?
Psyllium
163
What are osmotic laxatives?
Milk of magnesium, magnesium citrate, lactulose, polyethylene glycol
164
What are prokinetic laxatives?
Lubiprostone, linactolide (used for severe constipation)
165
What is a secretory laxative?
Castor oil
166
What is a stimulant laxative?
Bisacodyl
167
What are the criteria for IBS?
1. Recurrent abdominal pain for 3 days/month
| 2. 2+ of the following: improvement with defecation, change in frequency of stool, change in appearance of stool
168
What are alarm symptoms related to IBS?
Anemia, weight loss, family history of colorectal cancer/IBD/celiac
169
How is IBS managed?
1. Dietary changes
2. Pharmacologic therapy based on stool pattern
3. CBT, probiotics
