GI Final Exam Flashcards
(233 cards)
1
Q
What is the fibrous connective tissue capsule covering the liver?
A
Glisson’s capsule
2
Q
What is contained within the hilum of the liver?
A
• portal vein
• hepatic artery
• common bile duct
• lymphatic vessels
• nerves
3
Q
What is a classic liver lobule?
A
• hexagonal shape with portal canals at the corners of the hexagon and a central vein at the center
4
Q
What are the components of the portal canal?
A
• portal vein
• hepatic artery
• bile duct
5
Q
What is the space of Disse?
A
A space that lies between sinusoidal lining and surface of parenchymal cells: this is where blood can interact directly with the Enterocyte surface
6
Q
What is the appearance of liver hepatocytes?
A
• cells arranged in cords lining the sinusoids
• many Golgi and sER (eosinophilic)
• many ribosomes and rER (basophilic)
• glycogen and lipid (untrained)
• this creates the appearance of an eosinophilic cell with basophilic stippling
7
Q
Direction of blood flow in the liver
A
Portal vein —> central vein through hepatic sinusoids
8
Q
What are the bile canaliculi?
A
• located between adjacent hepatocytes, formed by their tight junctions
• contain small microvilli that extend into cannular lumen
• collect bile produced by hepatocytes
9
Q
What is the flow of bile through the liver?
A
Parenchyma (hepatocytes) —> bile canaliculi —> bile ducts (canal of Hering) —> hepatic duct —> cystic duct —> gallbladder
10
Q
What are the three perspectives for liver lobule microarchitecture?
A
- Classic lobule
- Portal lobule
- Acinus lobule
11
Q
The concepts of a classic liver lobule:
A
- blood flows from periphery of lobule to the center
- bile flows from the center of the lobule to the periphery
12
Q
The concepts of a portal liver lobule:
A
- portal Canal is the lobule center
- blood flows from the center of the lobuleto the periphery
- bile flows from the periphery of the lobule to the center
13
Q
The concepts of a liver acinus lobule:
A
- the center of the lobule is the terminal branch of the portal vein and hepatic artery
- blood flows from the center of the acinus to the periphery
- bile flows from the periphery of the acinus to the center
14
Q
What muscles make up the pelvic musculature?
A
• walls: piriformis, obturator internus
• floor: levator ani (pubococcygeus and iliococcygeus, puborectalis), coccygeus
15
Q
What muscles make up the pelvic musculature?
A
• walls: piriformis, obturator internus
• floor: levator ani, coccygeus
Levator ani= pubococcygeus and iliococcygeus
16
Q
Why does prolapse typically occur?
A
Injury to the perineal body
17
Q
What runs through the greater sciatic foramen?
A
• piriformis
• superior to piriformis: superior gluteal nerve, artery, vein
• inferior to piriformis: inferior gluteal artery, nerve, vein, sciatic nerve, pudendal nerve, internal pudendal artery/vein, posterior femoral cutaneous nerve, nerve to obturator internus and quadratus femoris
18
Q
What runs through the lesser sciatic foramen?
A
• pudendal nerve, internal pudendal artery and vein
19
Q
What runs through the obturator foramen?
A
• obturator nerve, artery, vein
20
Q
What LFTs indicate hepatocyte injury?
A
• AST, ALT, LDH
• all involved in gluconeogenesis pathway
• all increase during liver injury/disease
21
Q
Where is AST present?
A
In cytosol and mitochondria of the liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lungs, WBC and RBC
22
Q
Where is ALT present?
A
In the cytosol, mostly in the liver
23
Q
Where is LDH present?
A
In the cytosol everywhere: participates in glucogenesis in the liver and glycolysis everywhere else
24
Q
What LFTs indicate biliary damage/function?
A
• bilirubin, alkaline phosphatase, 5’-nucleotidase, and GGT (gammaglutamyl transferase)
25
Where is alkaline phosphatase located?
• microvilli of the bile canaliculus
• also present in bone, intestine, placenta, kidney, WBC (non-specific)
26
Where is 5’-nucleotidase localized?
• in the microvilli of the bile canaliculus (more specific to the liver than alk phos)
27
Where is GGT located?
• found in hepatocytes and bile duct cells
• sensitive for hepatobiliary disease, but not specific
28
What LFTs indicate hepatocyte function?
• albumin
• clotting factors (PT/PTT)
• these labs decrease in disease (albumin, clotting factors), therefore PT/PTT increase in disease
29
Mild ALT predominant elevation indicates:
• **hepatitis B
• hepatitis C
• acute viral hepatitis (A-E, EBV, CMV)**
• steatosis
• hemachromatosis/auto immune
• alpha one antitrypsin
• Wilsons disease
• celiac disease
30
Mild AST predominant elevation indicates:
• alcohol related liver injury
• cirrhosis
• steatosis
31
What are non-hepatic reasons for mild ALT/AST elevation?
Hemolysis, myopathy, thyroid disease, strenuous exercise, macro AST
32
What are the common causes of severe elevations of ALT/AST (15x the upper limit of normal)?
1. Drug induced (acetaminophen)
2. Occupational/environment (toluene, CCl4)
3. Ischemic hepatitis (Budd Chiari syndrome)
4. Viral hepatitis (A-E, herpes)
33
When do you typically see an elevated alkaline phosphatase that is physiologic and not pathologic?
In the third trimester of pregnancy (placenta), and adolescence (bone)
34
If alkaline phosphatase is chronically elevated, evaluate for:
* cholestatic liver disease
* infiltrative liver disease (cancer, sarcoidosis)
* biliary obstruction
35
When you have an elevated alkaline phosphatase, what confirms hepatic source?
Gammaglutamyl transferase (GGT) found in hepatocytes and bile duct cells
36
What drugs can cause an elevated GGT?
Carbamazepine, phenytoin, barbiturates
37
Blood from the G.I. system goes directly to the liver via what?
The portal vein
38
What are hepatic pit cells?
Liver associated lymphocytes. These natural killer cells protect against viruses and tumor cells
39
What are Kupfer cells?
Endocytic, phagocytic, macrophages
40
The liver converts excess protein and carbohydrates to what?
Blood proteins, glucose, and VLDL
41
How does the liver work to detoxify xenobiotics and metabolites?
• two phase reactions, where the first phase is to change the oxidation state to polar/reactive to induce higher solubility and then the second phase adds polar group to increase solubility
**1.) reduction, oxidation, hydroxylation, hydrolysis
2.) conjugation, sulfuration, methylation, glucuronidation**
42
What makes up phase 1 of the livers detoxifying capacity?
Cytochrome P450 enzymes using NADPH, sometimes NADH, and O2
43
What is an important class of phase 2 enzymes for liver detoxification?
Glutathione conjugation by **glutathione S transferases**
~ this is why depletion of the pool of reduced glutathione can exacerbate toxicity
44
What is the clinical presentation of acetaminophen toxicity?
1. Early: nausea, vomiting
2. 24-48 hours: ALT/AST increase, LDH increase, PTT/PT increase
3. 72-96 hours: jaundice, hepatomegaly, increased bilirubin, encephalopathy, hypotension, hypoglycemia, metabolic acidosis, death by organ failure
45
In acetaminophen poisoning, CYP2E1 converts acetaminophen to what?
**NAPQI**: this creates adducts on cell proteins and kills cells
~ maintaining a pool of reduced glutathione (N-acetyl cysteine) allows for shuttling of the pathway to create mercapturic acid and safe excretion through the kidneys
46
Which cells are most affected by NAPQI cell destruction?
Perivenal (near the central vein, zone 3)
47
What induces CYP2E1 expression, and increases the rate of NAPQI production?
**Alcohol.** This depletes NADPH, which is required to maintain the pool of reduced glutathione
48
What is the hallmark symptom of a glycogen storage disease?
Fasted hypoglycemia
49
Excess nitrogen that result from amino acid catabolism must be converted to urea for excretion. Where does urea’s nitrogen come from?
Free ammonia, and aspartate
50
The majority of excess nitrogen is transported from peripheral tissue to the liver in what form?
Amino acids: **glutamine and alanine**
51
What hepatocytes secrete Wnt?
Central vein endothelial cells
52
To avoid liver toxicity, how is glutamine handled in the liver?
• High concentrations of glutaminase and CPS1 at the periportal hepatocytes
• high concentrations of glutamine synthetase at perivenal hepatocytes
53
How does a gradient of Wnt concentration create a safe zone for a free ammonia?
It all allows free ammonia to be a substrate for the urea cycle, without free ammonia being released into the general circulation
54
What are the most common causes of acute hepatitis?
• hepatitis A, hepatitis E
• fecal-oral route, transmitted through food or water
55
What does hepatitis A look like?
ssRNA+ virus, non-envelope, icosahedral nucleocapsid, single-stranded positive genome, non-segmented (picornavirus)
~ incubation of 15 to 50 days
56
What does hepatitis look like?
RNA virus, icosahedral nucleocapsid, non-enveloped, single-stranded positive genome, non-segmented, hepeviridae
~ incubation of 15 to 60 days
57
What are the diagnostic criteria of hepatitis A?
1. Lab: Immunoglobulin M (IgM) for hepatitis A virus RNA
2. Case classification confirmed: clinical criteria for IgM anti-HAV or hepatitis A RNA detected by PCR/genotyping
~ also qualifies if clinical criteria in a person who had contact with a confirmed hepatitis A case 15-50 days prior to onset of symptoms
58
What is the treatment/post exposure prophylaxis for hepatitis A?
• treatment is symptomatic
• exposure prophylaxis is hepatitis A vaccine administered within two weeks of exposure, occasionally co-administration of GamaSTAN S/D immunoglobulin
59
Who is most at risk for hepatitis E severity?
• pregnant women, particularly in the third trimester
• undercooked pork, bear, deer meat eaters
60
What is hepatitis B?
• liver infection caused by interaction with infected body fluids that can lead to chronic viral hepatitis
• liver damage via host immune response mediated by cytotoxic T lymphocytes
• only 5% of cases become chronic
61
What is hepatitis C?
• liver infection caused by interaction with infected body fluids that can lead to chronic viral hepatitis
• liver damage via host immune response mediated by cytotoxic T lymphocytes
• 50% of cases become chronic
62
Which has a vaccine: hepatitis B or hepatitis C?
Hepatitis B. It is recommended for all children, commonly co-administered in a DTaP, or IPV
63
What does hepatitis B look like?
* dsDNA virus, Icosahedral nucleocapsid, enveloped, double-stranded partial genome (circular), hepadnaviridae
~ incubation time of 2 to 5 months
64
What does hepatitis C look like?
• RNA virus, icosahedral nucleocapsid, enveloped, linear single-stranded positive genome, flaviviridae family (just like yellow fever, dengue fever and tickborne encephalitis)
~ incubation time of 2 weeks to 6 months
65
What are the two most common routes of transmission for hepatitis B?
• percutaneous (puncture through the skin) with infectious blood/body fluid
• mucosal contact with infectious blood/body fluids
66
What makes hepatitis B so difficult to clear?
Covalently closed circular DNA (cccDNA) as the template for viral messenger RNA transcription
67
What are Dane particles?
Hepatitis B virus (HBV) virions — seen on EM
68
What are the three serological tests required for laboratory diagnosis of hepatitis B?
• hepatitis B surface antigen [HBsAg]
• hepatitis B surface antibody [anti-HBs]
• total hepatitis B core antibody [anti-HBc]
69
What indicates a chronic infection with hepatitis B?
• presence of HBsAg (surface antigen) for longer than **six months**
70
What is the treatment for hepatitis B?
* supportive, no alcohol
* antivirals: entecavir, tenofovir, iamivudine, adefovir, telbivudine
* interferons: Intron A, Peg-IFN
* liver transplant in severe cases
~ complete cure not possible, functional cure (undetectable serum antigen and HBV DNA, with residual cccDNA POSSIBLE)
71
Which hepatitis is most likely to cause hepatocellular carcinoma?
Hepatitis B— 12-300x greater risk
72
What is hepatitis D?
• only a viral genome, not virus
• ORF transcribed— encodes HDAg
• Super infection with HBV is required (replication tools from HBV needed for HDV)
73
Why is hepatitis C a “quasi species”?
It’s RNA dependent RNA polymerase (3'-5' repair inffective) is highly error prone— creating many subtypes
74
Where does hepatitis C replication occur?
All occurs in the cytosol, nucleus not required. Virus enters via pH dependent and/or clathrin-mediated endocytosis
75
What is a unique feature of hepatitis C replication?
• membranous Web: includes double membrane vesicles containing HCV nonstructural proteins, HCV RNA, ER membranes, and lipid droplets
76
What are the complications of chronic hepatitis C?
**Fibrosis, cirrhosis, liver cancer (hepatocellular carcinoma)**
**Non-hepatic complications:** diabetes, glomerulonephritis, cryoglobulinemia, porphyria cutanea tarda, non-Hodgkin’s lymphoma
77
What are the treatment options for hepatitis C?
1. Older: interference on plus the antiviral ribavirin
2. Newer: DAA therapy (90% cure rate)
78
What is direct acting antiviral (DAA) therapy?
* hepatitis C treatment targeting specific nonstructural virus proteins disrupting viral replication and infection
* PIs (protease inhibitor), NPIs (nucleoside polymerase inhibitor), NNPIs, and NS5A inhibitors
* **(sofosbuvir, velpatasvir, and voxilaprevir)**
79
What are common symptoms of yellow fever due to hepatic dysfunction?
Jaundice and councilman bodies
80
What enzyme is responsible for the conjugation of bilirubin?
UGT1A1: uridine diphosphate-glucuronyltransferase (peptide 1A) in the hepatocyte
81
Which enzymes are important for transporting conjugated bilirubin from the liver?
• MRP2: multi drug resistant protein 2
• OATP: organic anion transporting polypeptide
82
What are the causes of unconjugated (indirect) hyperbilirubinemia?
**1. Increased production:** hemolysis, ineffective erythropoiesis (folate deficiency, iron deficiency, anemia)
**2. Defects and conjugation, UGT1A1 activity:** defect (Gilbert syndrome, Crigler Najjar syndrome)
83
What is Gilbert syndrome?
* common clinically innocuous, unconjugated hyperbilirubinemia with otherwise normal liver chemistries
* polymorphism of gene encoding bilirubin UGT1A1 (unable to conjugate bilirubin)
84
What is Crigler Najjar syndrome?
• **type one:** severe UGT1A1 deficiency, fatal in neonatal period
• **type two (rare):** similar to Gilbert syndrome, milder UGT1A1 deficiency
85
What is bilirubin encephalopathy/Kernicterus?
• **hyperbilirubinemia** leading to babies who are lethargic, hypotonic/hypertonic, high-pitched cry, opisthotonos, and have seizures
• permanent neurological symptoms such as choreoathetosis, spasticity, **hearing loss,** ataxia, mental retardation may occur
86
What are the common causes of conjugated (direct) hyperbilirubinemia?
Parenchymal disease or obstruction:
• hepatitis, cirrhosis, medication/toxins
• defects in canalicular transport (MRP2, OATP)
• bile duct obstruction
87
What is the name of the disease due to decreased MRP2 activity, causing blackening of the liver?
Dubin Johnson syndrome
~ elevated conjugated bilirubin
88
What disease process results due to a decreased OATP activity?
Rotor syndrome
~ elevated conjugated bilirubin
89
What are the notable features of fulminant hepatitis?
Mental status changes, bleeding/easy bruising, ascites and edema
90
Which is more mild, acute or chronic hepatitis?
Chronic: however, it is more likely to lead to hepatic failure or hepatocellular cancer
91
(Acute/chronic) hepatitis is more likely to have cholestatic findings compared to only hepatocellular
Chronic is more likely to have cholestatic findings of elevated alkaline phosphatase, elevated GGT, and elevated bilirubin
92
What does ballooning degeneration in acute hepatitis look like?
93
When do you see ground glass cells?
Typically hepatitis B
94
What histological changes are seen in hepatitis C?
• fatty changes
• bile ducts maintained, not destroyed
95
What are the common causes of fulminant hepatitis/massive hepatic necrosis?
• acute viral hepatitis
• drug or toxin induced hepatitis (acetaminophen)
• vascular liver disease
• autoimmune hepatitis
• Wilson’s disease
96
What is the pattern of necrosis for viral hepatitis and autoimmune hepatitis?
Focal, random necrosis with inflammatory infiltration
97
What is the pattern of necrosis for drug toxicity or ischemic liver injury?
Zonal necrosis, non-inflammatory (primarily effects **zone 3, near the central vein**)
98
Ground glass hepatocytes in hepatitis B look like what?
Their appearance is due to the accumulation of HBV surface antigen within the hepatocyte
99
What are common morphological findings of hepatitis C?
* progressions to chronic hepatitis in 80 to 90%
* non-specific, variable fibrosis and cirrhosis
* **lymphoid aggregates and steatosis can be seen**
100
What does hepatitis D require in order to be infectious?
Coinfection or superinfection with hepatitis B
101
Hepatitis E has a mortality rate in 20% of what patient population?
Pregnant people
102
What are the genetic predispositions to autoimmune hepatitis?
• white: HLADR3
• Japanese: HLADR4
• South Americans: HLADRB1
~ female predominant (78%)
103
What are the autoantibodies that can be seen in autoimmune hepatitis?
**Type 1: adults, most common-**
• anti-nuclear antibodies (ANA)
• anti-smooth muscle actin antibodies (ASMA)
**Type 2: children-**
• anti-liver kidney microsome-1 (LKM-1)
104
What are the common pathological histology findings of autoimmune hepatitis?
• combination of lobular and portal/Periportal inflammation, often robust
• **plasma cells numerous**
105
How do you diagnose autoimmune hepatitis?
Clinical evidence of hepatitis +
1. Autoantibodies (ANA/ASMA or LKM)
2. Elevated serum IgG
3. Exclusion of viral/drug or toxic causes
4. Supportive histological findings
106
What’s the difference between steatosis and steatohepatitis?
**Steatosis** is only the fat deposition within hepatocytes, **steatohepatitis** is fat deposition with evidence of hepatocyte injury (biochemical and histologic)
107
What is the pattern of fatty deposits for alcoholic and non-alcoholic fatty liver disease?
Macrovesicular with some microvesicular steatosis
108
What generates a lot of NADH, leading to lipogenesis and reduced hepatocyte fatty acid oxidation?
Ethanol metabolism by alcohol dehydrogenase and acetaldehyde dehydrogenase
109
Is steatosis reversible with the cessation of alcohol consumption?
Yes
110
What are the microscopic features of alcoholic steatohepatitis?
• liver cell injury: swelling (ballooning degeneration) and necrosis
• Mallory bodies (cytokeratin aggregates)
• neutrophilic inflammation, clustered around degenerating hepatocytes
111
Progressive alcohol liver disease can lead to what?
Cirrhosis and deposition of collagen/fibrosis typically beginning in perivenular zone 3 region
~ TGF-beta responsible for collagen deposition
112
AST is typically 2x higher than ALT in what type of hepatitis?
**Alcoholic hepatitis** (every other hepatitis typically presents with a relatively higher ALT)
113
What is nonalcoholic fatty liver disease and what is it associated with?
• steatosis with little or no alcohol consumption
• associated with: obesity, DM2, hyper lipidemia, hypertension
~ currently the most common cause of chronic liver disease in the United States
114
What is cirrhosis?
• common end stage of chronic liver disease— extreme liver destruction replaced by fibrosis
• TGF-beta activates stellate cells in the space of Disse and they begin to lay down collagen
115
What is the lab evaluation of cirrhosis?
• cholestasis: elevated alkaline phosphatase, elevated bilirubin
• reduced synthetic function: low albumin and clotting factors (PT/PTT)
• AST/ALT maybe low/normal, due to loss of liver parenchyma
116
In cirrhosis, a combination of fibrosis and regeneration of hepatocytes leads to what?
Diffuse scarring and nodularity (typically irreversible, some reversibility with total cessation of alcohol consumption and eradication of hepatitis C)
117
What are the complications of cirrhosis?
• **hypoalbuminemia:** edema
• **clotting factor deficiencies:** bleeding
• **estrogen accumulation:** gynecomastia, Palmar erythema, spider angiomata
• **bilirubin accumulation:** jaundice
• **ammonia accumulation:** hepatic encephalopathy, AMS, asterixis and coma
118
What are the three portal hypertension/restrictions of blood flow through the liver, and which is the most common for cirrhosis?
• prehepatic: thrombosis/structural
• intrahepatic: cirrhosis
• posthepatic: hepatic vein obstruction, Budd-Chiari syndrome, right sided heart failure
119
What are the complications of portal hypertension?
• hepatic encephalopathy (ammonia)
• ascites
• formation of portosystemic venous shunts
• congestive splenomegaly
120
What is ascites?
• increased fluid in extravascular space with accumulation and abdominal cavity **(increased hydrostatic pressure in hepatic sinusoids due to fibrosis, decreased oncotic pressure due to loss of albumin production)**
121
What is spontaneous bacterial peritonitis?
A life-threatening bacterial infection of the ascitic fluid
122
What are the portosystemic shunts?
• esophageal varies
• hemorrhoids
• Caput medusae
123
Why does congestive splenomegaly occur in cirrhosis?
• decrease in clotting factors, increased bleeding—> massively expanded red pulp leading to sequestration of cellular blood elements
• thrombopenia can exacerbate bleeding tendencies, pancytopenia possible
124
What is Budd-Chiari syndrome?
* A hypercoagulable state (polycythemia vera) leading to obstruction of the hepatic veins
* presents with pain, hepatomegaly, and ascites
* hepatocellular pattern with transaminases up to 5x normal
125
In what condition would you see thrombi in the hepatic veins?
Budd-Chiari syndrome
126
How does right sided heart failure lead to liver failure?
• right sided heart failure causes passive congestion with dilated sinusoids and a progressive loss of centrilobular hepatocytes —> long-standing can lead to hepatic fibrosis
127
How does left sided heart failure cause liver failure?
Left sided heart failure causes hypoperfusion and ischemic and necrosis of centrilobular hepatocytes —> long-standing can lead to hepatic fibrosis (cardiac sclerosis)
128
What is the common gross finding of passive congestion/systemic circulatory compromise in the liver?
**nutmeg liver** creating a mottled appearance
129
What is the difference between right sided and left sided heart failure creating centrilobular (zone 3) congestion and necrosis?
• right sided heart failure: congestion > necrosis
• left sided heart failure: necrosis > congestion
130
What powers biosynthetic and detoxification reactions in the liver?
NADPH from the pentose phosphate pathway
131
How does glycosylation occur?
In the lumen of the endoplasmic reticulum of hepatocytes: the chain begins assembly on a molecule of **dolichol** and then transported to the Golgi for additional modification
132
What is phosphoglucomutase 1 deficiency?
• PGM1 is an enzyme essential for **glycogenolysis and glycogen** synthesis. Also important for generating **UDP-galactose, glycosylation intermediate**
• symptoms: hepatopathy, bifid uvula, dilated cardiomyopathy, hypoglycemia, myopathy, mental retardation
133
Without proper glycosylation, what happens to transferrin?
It cannot be created, iron cannot be transported. It is normally glycosylated with two identical glycol chains that terminate with two sialic acids
134
What works as treatment for PGM1 deficiency?
Dietary galactose supplementation
135
What hormone has three glycosylation sites, required for maturation of puberty in females?
**Leutinizing hormone (LH):** glycosylation stabilizes it in circulation and increases its affinity for its receptor **(without glycosylation, luteinizing hormone does not efficiently stimulate estrogen production)**
136
What hepatocytes are most susceptible to damage from acetaminophen toxicity?
Centrilobular (zone 3), where there is maximum CYP450 enzymes
137
What is a genetic variant that leads to increased susceptibility to liver toxicity when being treated for tuberculosis with isoniazid?
Variant of N-acetyltransferase (NAT2)
~ ALT > 5x normal, or ALT/alk phos ratio >5 (hepatocellular pattern)
138
What is hemachromatosis, and why does it lead to liver toxicity?
• Excessive iron absorption (or blood transfusion) leading to excess iron accumulating in the liver, pancreas, heart, joints
• **classic tetrad of: cirrhosis, hepatomegaly, abnormal skin pigmentation, diabetes, cardiac dysfunction**
139
Hemachromatosis can lead to what neurological symptoms?
Cognitive decline, gait difficulties, cerebellar ataxia, extrapyramidal dysfunction
~ all likely due to iron deposition in the **basal ganglia**
140
Iron deposition in the anterior pituitary and testicles due to hemachromatosis leads to what?
Hypogonadism; amenorrhea
in females, impotence in males
141
What are the most common genetic disorders leading to hereditary primary hemachromatosis?
Adults: **HFE, usually C282Y**
Children: **HAMP, and HJV**
142
What binds to a ferroportin (the iron influx channel at the basal surface of intestinal cells) and causes its degradation?
**Hepcidin** (produced by the HAMP gene)
143
Hemachromatosis will look like what histologically?
• iron deposits (brown cytoplasmic granules or positive Prussian blue stain)
• fibrosis with cirrhosis in advanced cases
144
What is the treatment of hemachromatosis?
Regular phlebotomy
145
What are the clinical manifestations of Wilson’s disease?
• liver hepatitis and failure
• tremors, muscle stiffness, troubles speaking, personality changes, anxiety, auditory or visual hallucinations **(psychosis)**
• Kaiser Fleischer ringed eyes
146
Mutation in what gene leads to Wilson’s disease?
**ATP7B gene** (a trans transmembrane copper transporting ATPase)
~ lab values will show a decreased serum ceruloplasmin and copper
147
What does the histology look like in a person with Wilson disease?
Similar to steatohepatitis, fatty change with focal hepatocyte necrosis, ballooning degeneration, and Mallory hyaline (**+ copper accumulation**)
148
What is the treatment of Wilson disease?
Copper chelation therapy with **penicillamine and trientine**
149
What is alpha-1 antitrypsin deficiency?
• autosomal recessive disorder caused by mutations in alpha-1 AT (typically an active protest inhibitor— inhibits neutrophil elastase)
• leads to: pulmonary disease (destruction), **liver disease (accumulation of misfolded alpha-1 AT the endoplasmic reticulum causing apoptosis of hepatocytes)**
150
Of the four genotypes for alpha-1 antitrypsin (M, S, Z, Null), which is the most pathogenic?
M is normal. Z is more pathogenic than S, however Null mutation results in no alpha1-AT expression (bad)
151
How does Alpha-1 anti-trypsin present in neonates?
• typically symptomatic with ZZ mutation
• neonatal hepatitis
• cholestasis
152
What is intrahepatic cholestasis?
• obstruction of the intrahepatic bile ducts
• caused by colon hepatitis, intra-hepatic atresia, contraceptive pills, antibiotics, pregnancy, tumors, sickle cell disease, or ductopenia
153
What is extrahepatic cholestasis?
• obstruction/stasis of the common bile duct and below
• caused by choledocolithiasis, benign bile duct structures, tumors, primary sclerosing colitis, and biliary atresia
154
Lack of bilirubin excretion (such as cholestasis), lead to what exam findings?
• icterus and jaundice
• dark urine (excess unconjugated bilirubin excreted by the kidneys)
• light colored, pale stool (pigment from conjugated bilirubin not present)
155
Lack of bile acid secretion, such cholestasis, leads to what clinical findings?
• pruritis
• fatigue and easy bruising/bleeding
156
Cholestasis sepsis
* inflammatory mediators such as LPS affect bile acid transporters leading to cholangitis
* effect is reduced bile flow, with predominant bile plugs at the portal-parenchymal interface
157
What is seen in an acute large bile duct obstruction?
• portal tract edema with neutrophil at the interface between portal tract and hepatocytes
• prolonged obstruction: ascending cholangitis and periportal fibrosis
158
What is a hallmark of ascending cholangitis?
• intestinal tract bacteria migrating up into the biliary tract due to stasis
• **neutrophils within the epithelial cell lining of the portal tract**
159
Chronic biliary obstruction (biliary cirrhosis) causes what types of nodules of the liver cells?
Puzzle piece rather than lobular
160
What is neonatal cholestasis? (non-obstructive)
• Present clinically at 1-2 months of age with prominent cholestatic signs and symptoms such as Icterus, jaundice, pale stool, dark urine, failure to thrive, hepatomegaly
• imaging studies will show normal biliary tree (distinguishing between biliary atresia)
• biopsy shows **giant cell hepatitis** pattern
161
What is extrahepatic biliary atresia (obstructive neonatal cholestasis)
• complete or partial obstruction of the extra hepatic biliary tree within the first three months of life
1.) perinatal form (80%) biliary tree develops normally, subsequently destroyed
2.) fetal form (20%) failure of normal development of the extrahepatic biliary tree
162
What is the pathology of extrahepatic biliary atresia?
• inflammation and fibrosis of the hepatic or common bile ducts
• extension to involve intrahepatic ducts is possible
• cirrhosis by 3-6 months of age
• Tx: Kasai procedure
163
What is primary biliary cholangitis (PBC)?
* autoimmune disorder with T cell mediated inflammatory destruction of **intrahepatic bile ducts**
* more common females, 40-50yo
* associated with other autoimmune disorders, risk for hepatocellular carcinoma following cirrhosis is increased
164
How is PBC diagnosed?
• LFTs: prominent cholestatic pattern
• serology: **positive AMA, positive ANA**
• florid duct lesion (chronic and granulomatous inflammation damaging bile ducts)
• **diagnosis established with elevated alkaline phosphatase for greater than six months, positive AMA, and characteristic histological findings**
165
What is the treatment of primary biliary cholangitis (PBC)?
• Ursodeoxycholic acid (UDCA)
~ stimulates biliary secretion, protects injured bile duct epithelial cells from acid, promotes detoxification, inhibits hepatocyte apoptosis, slows fibrosis
166
What is primary sclerosing cholangitis (PSC)?
• autoimmune inflammatory and fibrosing disease of large bile ducts affecting extrahepatic and large intrahepatic ducts
• more common in males
• highly associated with ulcerative colitis, increased risk of cholangiocarcinoma
167
How is PSC diagnosed?
* elevated alkaline phosphatase
* imaging: beading of large bile duct on ERCP/MRCP
* MHC association: HLA-B8
* positive at typical perinuclear anti-neutrophil cytoplasmic antibodies (AP-ANCA)
168
What is the histopathology of PSC?
* large intrahepatic bile duct and extrahepatic duct show epithelial injury and inflammation
* periductal **onion skinning**
* small intrahepatic bile ducts are spared
169
What is a choledochal cyst?
• congenital dilation of the common bile duct
• usually presents before age 10, more common in females
• presents with jaundice and abdominal pain
• complications: stones, pancreatitis, obstructive biliary liver disease, choleangiosarcoma
170
What is fibropolycystic disease?
* a variety of lesions that are due to congenital malformations of the biliary tree (ductal plate malformations)
* **Von Meyenburg** = innocuous lesion
* **congenital hepatic fibrosis** = presents in late childhood hepatosplenomegaly, portal hypertension, and NO hepatocellular dysfunction w/ increased risk for choleangiosarcoma
171
What does a von Meyenburg complex/bile duct hamartoma look like?
• irregular glands in a fibrotic stroma
172
What is Caroli disease?
Multifocal cystic dilation of the large intrahepatic bile duct seen in fibropolycystic disease.
**Combined with congenital hepatic fibrosis = Caroli syndrome**
173
What does congenital hepatic fibrosis look like histopathologically?
* portal tracts are expanded with fibrous tissue and irregular shaped bile ducts
* resembles cirrhosis, patients are at risk for portal hypertension
174
What bacteria from dental caries leads to pulmonary abscesses?
Actinomycosis (Gram + bacilli, annular and branching, yellow pigment sulfur clusters)
175
What pulmonary infectious agents are associated with alcoholism?
• Klebsiella pneumonia
• Myobacterium tuberculosis
176
What antibiotic typically causes closterioides difficile?
Clindamycin (metronidazole and vancomycin are used to treat c. Diff)
177
What is used to treat Trichinosis spiralis?
Albendazole and mebendazole
178
Determination of alcoholic hepatitis via labs includes what?
• AST: ALT ratio is 2:1
• AST is never >500
• elevated total bilirubin and PT
~ Tx: **prednisolone** reduces inflammation and improves mortality
179
What best describes the formation of ascites?
**Increased capillary hydrostatic pressure**
~ in combination with decreased capillary oncotic pressure
180
What is the most appropriate agent to treat ascites?
1. Start with spironolactone (potassium sparing diuretic)
2. Add furosemide (loop diuretic)
181
How is cirrhosis diagnosed?
Biopsy
• lab test include: elevated PT, decreased albumin. Can have normal LFTs
182
What are the physical findings of cirrhosis?
• Icterus
• palmar erythema
• muscle wasting
• spider angiomas
• portal hypertension
• dupuytren’s contracture
• gynecomastia
• parotid enlargement
• clubbing of digits
183
Portal hypertension causes what vascular change?
Increased splanchnic capillary hydrostatic pressure
184
Cirrhosis/ascites can cause what secondary problem?
Secondary hyperaldosteronism: increased RAAS activation causing volume retention and worse ascites
185
What is the pathophysiology of hepatorenal syndrome?
Decreased hepatic clearance of nitric oxide leading to kidney vasculature vasodilation (hypoperfusion)
186
What medication is given for hepatic encephalopathy (excess ammonia)?
**Lactulose:** a drug that creates an acidic environment in the intestinal lumen (osmotic laxative) NH3 is trapped as NH4 and excreted in feces
**Rifamixin:** RNA polymerase inhibitor, select gut bacteria that produces less NH3
187
What mushroom contains a chemical that inhibits RNA polymerase II?
Amanitin mushroom (produces alpha-amanitin)
188
Nausea and vomiting in children can lead to what?
Hypochloremia, hypokalemic metabolic alkalosis
189
What are the signs and symptoms of diabetic ketoacidosis and children?
• Kussmaul respirations
• weight loss
• polyuria/polydipsia
• acetone breath
• AMS and dehydration
• hyperglycemia
• metabolic acidosis
190
A patient that has bilious vomiting without abdominal distention on the first day of life typically has what GI problem?
Duodenal atresia
191
What is the primary cause of diarrhea in North America?
Viral gastroenteritis
192
What are the most common causative agents of infectious diarrhea?
* rotavirus
* norovirus
* Campylobacter
193
What can be the sole symptom of a child with COVID-19?
G.I. symptoms, diarrhea
194
What are the clinical history features that are atypical of viral gastroenteritis?
• fever
• abdominal pain
• blood/mucus in stool
• bilious/projectile vomiting
• duration >7 days
• increased your output
• altered consciousness
• international travel
• exposure to food, unsafe water, farm animals, reptiles
195
What are clinical exam features that are atypical of viral gastroenteritis?
• moderate to severe dehydration
• bulging fontanelle
• hyponatremia with hyperkalemia
• respiratory abnormalities
• abdominal distention/focal tenderness/mass
• petechiae
196
What are clinical lab values that are atypical of viral gastroenteritis?
• abnormal CBC
• elevated CRP
• fecal leukocytes
• persistent diarrhea
197
What are the organisms that cause bloody diarrhea?
**SSCCEEYAA, bloody diarrhea**
• salmonella
• Shigella
• campylobacter
• c. diff
• EIEC
• EHEC
• Yersinia enterocolitis
• amoeba
• aeromonas
198
What is an objective measure when a evaluating dehydration of children?
**percentage of weight loss**
* mild: 3-5%
* moderate: 6-9%
* severe: >10%
199
What is the typical IV treatment of diarrhea in children?
• typically in children >10% dehydrated based on weight
• **20mL/Kg of NS or D5NS**
200
What is colic in infants?
* inconsolable crying associated with drawing up the legs and gaseous distention (due to hypomotility, constipation)
* diagnosis of exclusion, no treatment
* **starts at 3 weeks, and peaks at week 6**
201
What is recurrent abdominal pain syndrome?
• two distinct peaks of frequency (first between 5-7 and second between 8-12) due to separation anxiety
• Tx: emphasize normality by remaining in school, continuing activities and resuming normal diet
202
What is the number one genetic disorder of all time?
Lactose intolerance (lactase deficiency)
203
What are the treatments of constipation in children?
* polyethylene glycol (MiraLAX)
* milk of magnesia (1-3mL/Kg/day)
* mineral oil
* sorbitol
204
What is a liver hemangioma?
• most common benign liver mass
• commonly small and subcapsular, with Caverness histology and large thin walled vessels
• incidental detection
205
What is focal nodular hyperplasia?
• common benign liver mass found an adult women age 20-50
• arterial malformation causing altered blood flow **(both hyperperfusion and hypoperfusion triggering regeneration/reactive hyperplasia of hepatocytes)**
206
What hereditary disorder has a high incidence of focal nodular hyperplasia?
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
207
What does focal nodular hyperplasia look like?
* homogenous enhancing mass with a central scar (scar contains thick walled arterial vessels without corresponding bile ducts)
* benign regenerative nodules of hepatocytes separated by thick fibrous bands that radiate from the central scar
208
What causes a hepatic abscess?
• majority are bacteria (pyogenic) can be amoebic, parasitic, fungal
• most common etiology is **biliary:** ascending infection, cholangitis usually associated with obstructive cholestasis
209
What typically causes hepatocellular adenoma (benign neoplasm more often seen in young women)?
• **oral contraceptives, anabolic steroids, obesity, metabolic syndrome**
• typically detected in incidentally- tumors >5cm have risk for hemorrhage/malignancy
210
When is hepatocellular adenoma excised?
1. > 5cm due to risk of intra-abdominal hemorrhage
2. If beta-catenin mutation due to risk of malignant transformation
Only monitored: If small, with cessation of OCP/anabolic steroids
211
What are the pathological features of hepatocellular adenoma?
• discrete mass, sometimes hemorrhagic, sometimes multiple
• Unpaired arteries are seen, **no portal triads— only artery, no bile duct or vein associated**
212
What are the variant types of hepatocellular adenoma?
1. **HNF1A:** diffuse change, **LFABP1 negative**, associated with diabetes, females, minimal risk for HCC
2. **Beta-catenin:** Similar to well differentiated HCC, Associated with males, anabolic steroids, **HCC**
3. **Inflammatory:** dilated sinusoid and inflammatory cells, **CRP stain and serum amyloid A stain**, associated with obesity, females
213
What is hepatoblastoma?
• malignant liver tumor of early childhood, less than three years old
• presents with abdominal swelling, occasionally cholestatic symptoms (jaundice, pruritus)
• activation of WNT signaling and nuclear beta-catenin expression **(fetal and embryonal hepatocytes)**
214
What are the associated syndromes with hepatoblastoma?
• familial adenomatous polyposis (FAP)
• Beckwith- Wiedeman syndrome
~ tumor can present with embryonal/fetal liver cells and mesenchymal tissue such as bone
215
What is associated with hepatocellular carcinoma?
• chronic hepatitis B
• cirrhosis
• males
• hemachromatosis
• alpha-1 anti-trypsin
• pathways: **TERT/telomerase overexpression, beta-catenin, TP53**
• increased alpha-fetoprotein (AFP)
216
What is a fibrolamellar hepatocellular carcinoma?
• adolescent and young adult tumor
• no known risk factors
• normal serum AFP
• presents as a solid tumor in otherwise normal liver, thick plates and nests of malignant hepatocytes separated by dense bands of lamellar fibrous tissue
217
What is cholangiocarcinoma, and what is it associated with?
• malignant adenocarcinoma of the bile duct epithelium
• **intrahepatic:** intrahepatic cholangiocarcinoma
• **extrahepatic:** biliary adenocarcinoma, Klatskin tumor
• **risk factors: liver flukes, primary sclerosing cholangitis, hepatolithiasis, HCC**
218
Which tumors are found sooner, intrahepatic or extrahepatic?
**Extrahepatic:** they are more likely to completely obstruct flow of bile even with a small tumor. May cause jaundice and pruritus earlier at a resectable stage
219
What causes angiosarcoma of the liver?
1. Vinyl chloride
2. Arsenic
3. Thorotrast
220
What is the most common malignancy found in the liver?
**Metastasis from somewhere else:** colon, lung, breast, pancreas. Typically multiple nodules, presents with isolated elevation of alkaline phosphatase
221
Malrotation in development of the G.I. tract leads to what?
• ligament of Treitz on the right side of the abdomen and does not cross the midline
• bilious emesis, lethargy, toxic
• Ladd’s procedure to fix
222
What is the diagnostic test of choice for pyloric stenosis?
Ultrasound: shows a 3 mm thick, 15 mm length obstruction
223
What is the triad of symptoms for intussusception?
1. Colicky abdominal pain
2. Bilious emesis
3. Currant jelly stools
224
What is the typical Management of intussusception?
Barium enema: 80% success rate, can be done twice if needed. Third time occurrence is indication for surgery
225
Why are 12 to 18–year-olds most likely to get appendicitis?
That age is associated with the greatest number of lymphoid follicles present (lymphoid hyperplasia)
226
What are common labs that can be seen with appendicitis?
• high neutrophil count
• mild elevation in WBC (High, 15k+, indicates perforation)
• urinalysis may show sterile pyuria (WBC in urine without bacteria)
227
Meckel diverticulum is associated with what type of hernia?
Littre’s hernia
228
What is a common indication of Hirschsprung disease?
Failure to pass meconium in the first 24 hours
229
Omphaloceles are associated with what karyotype abnormalities?
• Trisomy 13, 18, 21
• also associated with other malformations: cardiac, MS, G.I., GU, and with Beckwith-Wiedmann syndrome
**~bad baby, healthy bowels**
230
What is seen in Beckwith-Wiedmann syndrome?
• omphalocele
• hyperinsulinemia
• macroglossia
231
Do babies with Gastroschisis have other comorbidities?
Typically no, **bad bowel, healthy baby**
232
The lining of the G.I. tract is from what embryological layer?
Endoderm
233
Smooth muscle and connective tissue in the G.I. tract are derived from what embryological layer?
Splanchnic mesoderm
