Week 7 (Hepatobiliary) Flashcards

Question

Predominant manifestations of liver disease

Answer 1

**Acute hepatocellular injury** **Biliary dysfunction** **Cirrhosis** **Hepatic masses**

Answer 2

**Toxins**: dose-dependent, idiosyncratic **Infectious**: viral, bacterial, parasitic, fungal **Neoplastic**: malignant, benign, hepatic, metastatic **Metabolic**: pediatric, adult onset **Autoimmune**: hepatocyte, biliary **Vascular**: pre, intra, post-sinusoidal **Biliary**: parenchymal, obstructive **Systemic**

Answer 3

**GI** **Reproductive** **Breast** **Lung** **Lymphoma** **Melanoma**

Answer 4

**Benign**: focal nodular hyperplasia, **hepatocellular adenoma**, macroregenerative nodule **Malignant**: hepatocellular carcinoma, fibrolamellar hepatocellular, hepatoblastoma

Answer 5

**Benign**: bile duct adenoma, biliary microhamartoma, biliary papillomatosis, biliary cystadenoma **Malignant**: intrahepatic cholangiocarcinoma, biliary cystadenocarcinoma

Answer 6

Non-alcoholic **fatty** **liver** disorders (now more tx done for this than for alcoholic liver!) **Pregnancy**-related liver diseases

Answer 7

**Autoimmune hepatitis (AIH)** **Primary biliary cirrhosis (PBC)** **Primary sclerosing cholangitis (PSC)** Overlap syndromes

Answer 8

**Arterial**: ischemic necrosis (ischemia to liver usually due to heart problem/hypotension), hepatic infarction **Sinusoidal**: peliosis hepatis **Venous**: Budd-Chiari syndrome, sinusoidal obstruction syndrome (VOD), congestive hepatopathy (NRH) **Portal**: portal vein thrombosis, splenic vein thrombosis

Answer 9

**Obstructive**: stones, neoplasm, trauma, cystic fibrosis **Hepatocellular**: acute injury, cirrhosis, hereditary **Biliary epithelium**: PBC, PSC, ascending cholangitis

Answer 10

Sarcoidosis Amyloidosis Sickle cell anemia Sepsis Post-operative cholestasis Rheumatoid arthritis Lupus

Answer 11

Acute and self-limited condition resulting from **acute hepatocyte necrosis** or **malfunction** Clinical presentation ranges from **asymptomatic** lab test abnormalities to life-threatening **fulminant hepatic failure** Etiology: **medications, toxins, viruses, autoimmune, metabolic, vascular**

Answer 12

**Irreversible** condition of diffuse destruction and **regeneration** of hepatocytes in which **scar tissue** (fibrosis??) has resulted in derangement of lobular and vascular architecture Clinical presentation ranges from **asymptomatic** **histopathologic** cirrhosis to **decompensated** cirrhosis with life-threatening complications

Answer 13

Any of a variety of disorders exhibiting **jaundice** as the predominant abnormality Clinical presentation includes **asymptomatic** (as benign bile transport abnormalities) to **acute obstructive jaundice** (with colangitis) to chronic **irreversible** **PBC** or **PSC** Etiologies: **obstruction**, **hepatocellular** or **biliary** **injury** or malfunction

Answer 14

Any of a variety of processes which manifest as a discrete hepatic **lesion** on imaging or histopathological studies Clinical presentations range from **transient** **pseudotumors** caused by focal fat to benign **hemangiomas** to **hepatocellular carcinoma**

Answer 15

**Hep B, Hep C**, HHC, cirrhosis --\> HCC **PSC** --\> cholangiocarcinoma **Estrogens** --\> hepatic adenomas Common **bacteria**, ameba --\> abscesses **Rheumatoid arthritis** --\> non-cirrhotic nodules **Steatosis** --\> pseudotumors **Polycystic disease, ecchinococcus** --\> hepatic cysts

Answer 16

**Symptoms**: jaundice, dark urine, clay colored stool, abdominal pain, itching, GI bleeding, increased abdominal girth, changes in mental status **Physical exam**: oral lesions, JVD, ascites, palpable liver or spleen, hepatic bruit, Cruveilhier-Baumgarten murmur, shifting dullness **Lab tests**: CBC, liver panel, renal tests, serologies, iron studies, uric acid **Imaging**: ultrasound, CT scan, MRI, nuclear medicine scan, PET scan **Biopsy**

Answer 17

**PMH**: diabetes, heart disease, lung disease, neurologic diseases, autoimmune diseases **PSH**: CCY, biliary or abdominal surgeries **FH**: hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency, DM, viral hepatitis **SH**: alcohol abuse, IVDA, recreational drugs, tattoos, blood transfusions, acupuncture, recent travel, sexual behavior **Meds**: acetaminophen, amiodarone, INH, herbs, alternative meds

Answer 18

Tests of **hepatocyte** **damage**: AST (SGOT) and ALT (SGPT) Tests of **cholestasis**: alkaline phosphatase, GGT, bilirubin Tests of liver **synthetic function**: prothrombin time, albumin

Answer 19

Cell injury results in **aminotransferase leakage** Aspartate aminotransferase (**AST**): cytosolic and mitochondrial enzyme found in **liver, muscle, kidney and pancreas** Alanine aminotransferase (**ALT**): cytosolic enzyme found in **liver**

Answer 20

**Alkaline phosphatase** (AP): reflects increased **synthesis** and **release** into serum; found in small bile ducts, bone, placenta and intestine Gamma-glutamyl transferase (**GGT**): inducible microsomal enzyme, little found in bone or placenta **Bilirubin**: produced as a breakdown product of hemoglobin; **conjugated** and **excreted** by the liver

Answer 21

Prothrombin time (**PT**): liver synthesizes major **coagulation** **factors**, except 8; PT is dependent on vitamin K dependent factors; coag factors have short half-life (6 hours for factor 7) **Albumin** (Alb): synthesized by liver but dependent on nutrition and pathological losses; 3 week half-life

Answer 22

**Hepatocellular** injury **Canalicular** injury **Microscopic duct** injury **Macroscopic duct** injury (intrahepatic or extrahepatic)

Answer 23

**Bile canaliculus**: hepatocellular injury (viral, alcoholic hepatitis), drugs, pregnancy **Bile ductule**: drugs (cholangiolitis) **Portal tract bile ductule**: primary biliary cirrhosis, intrahepatic biliary atresia **Medium** and **large interlobular bile ducts**: sclerosing cholangitis, cholangiocarcinoma

Answer 24

Numerous **drugs** **Acute alcoholic** injury **Ischemia** **Postoperative**

Answer 25

**Obstruction** and/or **injury** of bile ducts of any size may result in cholestasis Distinction between various types of bile duct injury often requires combination of histologic radiographic and serologic studies

Answer 26

**Primary biliary cirrhosis** (**PBC**)/**autoimmune cholangitis**: immune mediated destruction of small (interlobular) bile ducts **Drugs**

Answer 27

**Autoimmune** disease that results in **destruction** of **small bile ducts** (within the liver!) Mononuclear inflammatory lesions **centered on small bile ducts** **Granulomas** often present (histiocytes surrounded by lymphocytes); interface with surrounding parenchyma is pretty smooth which means is biliary disease Bile flow interrupted --\> **upstream** portal areas expand/become inflamed **Proliferating** ductules/ductal reaction **Portal tract scarring** leads to bridging **fibrosis** and ultimately **cirrhosis**

Answer 28

**Cholangiocarcinoma** (obstructs the duct and prevents bile from getting out) **Caroli's disease** (congenital cystic dilation of large bile ducts) Primary sclerosing cholangitis (**PSC**)

Answer 29

Primary sclerosing cholangitis (**PSC**): autoimmune mediated destruction of large (extrahepatic or intra (?) bile ducts), frequent association with UC, severity of 2 diseases is unrelated **Cholangiocarcinoma** **Pancreatic carcinoma** **Gallstones**

Answer 30

A progressive **inflammatory** disease: **fibrosis** of **LARGE** **intra and extrahepatic bile ducts** **Cholangiogram** demonstrates **strictures** in large duct(s) (**beads** on a string)--liver biopsy/histology doesn't always tell you diff between PSC and PBC (need cholangiogram) Increased risk of **cholangiocarcinoma** Histology: **nonspecific** (cannot be used to distinguish from other causes of large duct obstruction); large portal areas and ducts (early on, **concentric periductal edema** and **mononuclear inflammation**; later on **concentric fibrosis** (onion skin fibrosis) and ultimately fibrous **obliteration of bile duct**); portal tract scarring leads to bridging fibrosis and ultimately cirrhosis Elevated p-ANCA

Answer 31

**Elimination** of waste products: insufficiently water soluble substances that cannot be excreted in urine (**bilirubin**, **cholesterol**, others) Bile salts/acids augment **absorption of dietary fat** (reabsorbed in terminal ileum)

Answer 32

Causes: alteration in **composition** of bile, **stasis** (reduced contractility of gallbladder), **infection** Composed of **cholesterol, bilirubin, bile salts (Ca2+)** Types of gallstones: **cholesterol** stones contain \<50% crystalline cholesterol; **pigment** stones contain \<50% cholesterol (**black** vs. **brown** pigment stones) Formation of **cholesterol** stones: **supersaturation**, **hypomotility** of gall bladder, **nucleation** into cholesterol crystals, **mucous hypersecretion**

Answer 33

Cholesterol is solubilized by bile salts and phospholipids (lecithins) When the concentration of cholesterol **exceeds the solubilizing capacity of the bile**, supersaturation occurs and **crystals** form **Hypersecretion** of cholesterol is most common condition associated with gall stones **Decreased production of bile salts** or phospholipid **Decreased reabsorption of bile salts** in terminal ileum

Answer 34

High cholesterol concentration is toxic to the gall bladder: **Decreases wall motility** and promotes crystal formation Causes **mucous hypersecretion** and enhances agglomeration of cholesterol crystals into stones

Answer 35

**Industrial society 25%** **Native Americans** of first migration (Pima, Navajo, Hopi) 75% **Increasing age** **Obesity** **Female gender**

Answer 36

**Estrogen** increases **LDL uptake** (increased cholesterol **uptake** by liver) **Estrogen** increases **HMG CoA reductase** activity (increased cholesterol **production**) **Progesterone** **decreases** **gallbladder contractility**

Answer 37

Bile salts **reabsorbed** in **terminal ileum** Normally negative feedback causes decreased bile salt production by the liver **Abnormally increased negative feedback** results in decreased concentration of bile salts in bile (**supersaturation**)

Answer 38

Increased concentration of **unconjugated** **bilirubin** in bile Black: excess unconjugated bilirubin; derived from **increased RBC breakdown** (hemolytic anemia, G6PD, hemoglobinopathies, prosthetic heart valves), congenital defects in UDPGT, inflammatory conditions of terminal ileum

Answer 39

Increased concentration of **unconjugated** bilirubin in bile Brown: **bacterial** and **parasitic** infestation of **biliary tree** (organisms elaborate **hydrolases** which **deconjugate** bile)

Answer 40

**90%** of patients with **cholecystitis** have **gall stones** Only **20-30%** of patients with **stones** develop clinically evident **cholecystitis**

Answer 41

**Calculous**: **90%** of cholecystitis; stone obstructing **cystic duct**; can happen in **anyone** **Acalculous** probably **ischemic** (deprive GB of blood, get disease in GB wall): postoperative (nonbiliary), trauma, burns, multisystem organ failure, sepsis; no stone or structural obstruction; usually happens in hospital, as the **result of something else**

Answer 42

Most cases is **no prior history of acute cholecystitis** Biliary colic, **RUQ pain** Low grade inflammation; fibrotic, thickened wall **Rokitansky-Aschoff sinuses**: chronically inflamed mucosa proliferates in the form of outpouchings

Answer 43

This happens because **blood** **can't get out** of the liver: Thrombosis of hepatic artery Cardiac tamponade Tumor compressing hepatic vein Drug injury of central vein endothelium that causes thrombosis

Answer 44

**Acute** hepatitis has inflammation in **lobular** areas **Chronic** hepatitis has inflammation in **portal** areas

Answer 45

Means that inflammatory cells have **left the portal tract** by breaking through/**exiting** the **limiting plate**

Answer 46

**Steatohepatitis** **Alpha1 antitrypsin disease** **Hemochromatosis** **Wilson disease**

Answer 47

Porphyrin Carbohydrate (glycogen storage diseases, hereditary fructose intolerance, galactosemia) Glycoprotein (mucopolysacharidoses, mucolipidoses) Bilirubin metabolism Note: we won't talk about these diseases though

Answer 48

**Alcoholic** steatohepatitis **Non-alcoholic** steatohepatitis (NASH) Note: these cannot be reliably distinguished by histology

Answer 49

**NASH** is linked to **metabolic syndrome**, a variably defined syndrome characterized by: **Insulin resistance** **Type 2 DM** **Obesity** **Hyperlipidemia** Drugs?

Answer 50

**Steatosis**: reversible accumulation of **lipid** within cytoplasm of hepatocytes **Inflammation**: primarly **lobular**, less portal than in chronic viral hepatitis; lymphocytes and neutrophils **Ballooning** hepatocytes: **lysis** of cells **Mallory** **bodies**: Mallory's hyaline/alcoholic hyaline; **cytoplasmic** **inclusions** composed of cytokeratins, ubiquitin, others (not as well formed in NASH, but not best way to distinguish) **Pericellular fibrosis**: fibrosis around cells (not bridging)

Answer 51

**Macrovesicular** **steatosis**: droplets are generally larger than the nucleus, often pushing it to the **side** of the cell; **common** to have macro or mixed macro/microsteatosis **Microvesicular** **steatosis**: cells appear **foamy** due to much smaller size of vacuoles; **rare** to have a condition that has only microvesicular steatosis (associated with necrosis and steatohepatitis)

Answer 52

Most of the fibrosis (and damage in general) is lobular/**pericentral** (around central vein, **zone 3**) Relatively less portal fibrosis than in chronic viral hepatitis **Central to central bridging**

Answer 53

Disease activity including amount of fat can wax and wane **Steatosis** + some manifestation of **progressive injury**: steatosis alone is reversible; **Mallory bodies**, **ballooning** cells and **pericellular**/lobular **fibrosis** are the best indicators of progressive disease

Answer 54

Conditions that cause **pure microvesicular** steatosis are **rare** and indicative of severe **mitochondrial dysfunction** Frequently associated with **necrosis** and therefore steatohepatitis Results from impairment of mitochondrial beta oxidation which causes **buildup in fatty acids** Syndromes with primarily microvesicular steatosis: **Reye's** syndrome, fatty liver of **pregnancy**, foamy degeneration/a particularly aggressive variant of **alcoholic** liver disease, **drugs** (valproic acid toxicity, IV tetracycline), **mitochondrial** **cytopathies**

Answer 55

Alpha 1 antitrypsin is a **protease inhibitor** **Enzyme deficiency** (in lungs) and a **storage disease** (in liver) Variable clinical presentation (**neonatal** cholestasis, "cryptogenic cirrhosis" as an **adult**) Histology: **eosinophilic** cytoplasmic globules in **hepatocytes** Genetics: more than 75 alleles identified; M is normal/most common allele; **Z is allele in disease** (**lysine** to **glutamine** sub at **342**) **ZZ have 15% enzyme activity** compared to normal, resulting in an **enzyme deficiency** Abnormal alpha 1 antitrypsin protein cannot be properly processed by cells and **accumulates** in **hepatocytes** resulting in a storage disease **Null** **alleles**: no protein made, results in enzyme deficiency but **no storage disease**

Answer 56

**Lung**: ZZ phenotype has **pulmonary** **emphysema** because decreased enzyme activity allows an **elastase** made by neutrophils to go **"unchecked"** causing **tissue damage** resulting in emphysema **Liver**: only a **minority** of ZZ adults have clinically evident liver disease (cholestasis; prob have **biochemical** evidence of liver disease though), but **abnormal** **protein** **accumulates** in ER and can be seen on tissue sections as eosinophilic globules in cytoplasm of hepatocytes; only 10% develop cirrhosis Note: **"second hit"** hypothesized to be necessary for clinical liver disease

Answer 57

Neonatal (giant cell) **hepatitis** **Cholestasis** due to biliary disease (w/**jaundice**) **Hepatomegaly** **Acholic (pale) stools** Most **spontaneously** **regress** within 6 months Small percent go on to **liver failure**

Answer 58

Present with clinical features of **chronic liver disease** Most have **no history** of neonatal or pediatric disease Most are in **liver failure** within **2 years** of presentation

Answer 59

**Cytoplasmic** **globules**: accumulation of abnormal protein **Chronic** **hepatitis** with **interface** and **lobular** **activity**, **periportal fibrosis** of varying severity (can mimic viral hepatitis) **Cirrhosis** frequently seen at presentation

Answer 60

Pathologic **accumulation** of **iron** in **parenchymal cells** of the liver and other organs: **hereditary** (**primary**) or **secondary** (underlying condition causes **excess iron**--hemosiderosis) **Parenchymal** (hepatocellular) **hemosiderin** is derived via receptor mediated uptake from circulating **transferrin** and **ferritin** More in males, 40-50s Or females in 50-60s via loss of iron thru menstruation

Answer 61

**Ferritin** Not visible unless present in large quantities

Answer 62

**Insoluble**, end stage **product of ferritin degradation** Refractile **yellow** granular inclusions in cytoplasm **Increases** as amount of iron increases

Answer 63

1) Parenchymal: **hepatocytes** 2) Reticuloendothelial: **Kupffer cells**

Answer 64

1) Parenchymal (**hepatocellular**) hemosiderin is derived primarily via receptor mediated uptake from circulating **transferrin** and **ferritin** (this is mode of uptake in **genetic** **hemochromatosis**) 2) Reticuloendothelial (**Kupffer cell**) hemosiderin is derived primarily from **senescent RBCs** (get iron buildup in Kupffer cells in: **secondary hemochromatosis**, repeated **blood transfusions**, hemolysis, Bantu siderosis)

Answer 65

**Early** in disease, **easy** to tell if iron is in hepatocytes or in Kupffer cells As **hemosiderin** **accumulates** it causes **hepatocellular** **damage** and **necrosis** --\> then hemosiderin is **released from hepatocytes** and taken up by **Kupffer cells** In **later** stages of diesase, as hemosiderin accumulates in Kupffer cells, it becomes **harder** to tell whether disease is **primary** (hemosiderin in hepatocytes) or **secondary** (hemosiderin in Kupffer cells)

Answer 66

Gradually increasing **hepatocellular** **iron** in architecturally normal liver **No inflammation** WIth increasing amounts of iron, get **chronic hepatitis** with **interface** activity and **lobular** activity, **fibrosis** and **cirrhosis**

Answer 67

**Excess iron** damages hepatocytes by: Production of **free radicals** which cause membrane phospholipid peroxidation Direct stimulation of **collagen** **production** Interactions with **DNA** (increased risk for HCC above that for just cirrhosis)

Answer 68

Autosomal recessive **HFE** **gene** on chromosome 6: mutation in HFE results in **increased absorption of iron** from GI tract Prevalence of HFE mutation is 6% in northern Europeans (0.45% homo; 9% hetero) Not all homozygotes have excess iron There are cases of genetic hemochromatosis with **no mutation of HFE** (other genes involved, esp in non-northern Europeans)

Answer 69

**Liver**: most commonly involved organ **Heart**: secondary cardiomyopathy **Pancreas**: diabetes **Skin**: bronze (bronze diabetes) Involvement of these organs is rare in secondary HFE

Answer 70

Autosomal recessive disorder Mutation in copper transporting ATPase Accumulation of toxic levels of **copper** (in liver, brain, eye) Excess copper is eliminated from the body by excretion into bile (this pathway is disturbed in Wilson disease) **Defective biliary excretion** of copper leads to buildup and excess copper catalyzes production of **free** **oxygen radicals** Clinical presentation: **fulminant hepatic failure**, chronic injury mimicking chronic viral hepatitis (**cirrhosis**), toxic injury to **CNS** (basal ganglia), deposits in cornea (**Kayser-Fleischer rings**); **decreased ceruloplasmin** **Gene ATP7B** on chromosome 13 is a transmembrane copper binding ATPase on the canalicular membrane More than 30 mutations identified and most patients with Wilson's are **compound heterozygotes** (2 diff mutations) Treatment: give metalloproteinases (same tx for hemochromatosis)

Answer 71

**Early** on, have **fatty** **change** **Midcourse**, have **chronic hepatitis** (resembles viral) often with fatty change **Later**, have **cirrhosis** **Massive hepatic necrosis** resulting in **acute liver failure** can occur at any stage

Answer 72

**Chronic** **hepatitis**: low serum **ceruloplasmin**, increased **urine** **copper**, low uric acid (renal tubular acidosis) **Fulminant** **failure**: low **alkaline phosphatase**, hemolysis, renal failure, low uric acid

Answer 73

If you have a **large duct obstruction**, you will have **periductal** **edema** and **fibrosis** (onion skin fibrosis?) around the small ducts that are **upstream**

Answer 74

Bile duct **carcinoma** Enlarged **lymph node** **Sclerosing cholangitis** Postop **stricture** **Congenital biliary atresia** Pancreatic carcinoma **Gallstone** Carcinoma of Ampulla of Vater

Answer 75

Result of **cholesterolosis** Villi become packed with **foamy macrophages** that have lots of cholesterol, and macroscopically see them Gallbladder has **flecks** (villi) on it and looks like a strawberry

Answer 76

**Proteases 90%** **Amylase** 7% **Lipases** 2% Nucleases \<1%

Answer 77

Pathogenesis: interstitial **liberation** and **activation** of its own **enzymes**, occurs in spite of intrinsic protective mechanisms (probably somehow due to local inflammation/cytokines) Etiology: **alcohol**, **biliary**, idiopathic, other (autoimmune, drug-induced, iatrogenic (ERCP always causes amylase to go up but usually doesn't cause acute pancreatitis), IBD-related, infectious, inherited, metabolic, neoplastic, structural, toxic, traumatic, vascular) Symptoms: **abdominal** **pain**, increased pancreatic **enzymes** in serum Histology: **inflammation**, **edema**, fat **necrosis**, **hemorrhage**

Answer 78

**Proenzymes** within the cell Isolated compartments (**granules**) with **inhibitors** Secreted as proenzymes Activated only in **gut lumen**

Answer 79

**Insult** --\> **zymogen** activation, generation of **inflammatory** mediators, **ischemia** --\> inflammation and ischemia --\> 1) **Necrosis**, **apoptosis** 2) Systemic **inflammatory** response, **multi-organ failure** Note: also **neurogenic** **stimulation** causes inflammation and ischemia

Answer 80

**Sphincter** of Oddi **spasm** Stimulation of **CCK** and **secretin** release **Abnormal** **blood flow** and secretion Toxic **metabolites** (non-oxidative, oxidative) Sensitization to CCK (**zymogen** activation, **cytokine** generation)

Answer 81

Not totally understood Common channel theory: gallstone passing through common bile duct into duodenum and could obstruct and cause bile reflux which could injure pancreas? Pancreatic duct obstruction: unlikely cause because if you ligate bile duct, get atrophy, not pancreatitis!

Answer 82

**TGs** lysed into **FFAs** which are **toxic** to the pancreas Rare cause of **acute pancreatitis** but may cause **chronic** pancreatitis also (rare for something to cause both!) Serum triglycerides usually \>1000 mg/dL Can be **drug-induced** (alcohol, estrogens, isotretinoin, HIV-protease inhibitors)

Answer 83

Serum **enzymes** (lipase and amylase): if **\>3x normal**, then good indication of acute pancreatitis **Ultrasound**: best to see **gallstones** **CT**: detects **edema**, **calcifications**, **fluid** collections CT with **IV contrast**: detects **necrosis**

Answer 84

**Amylase** only: paroditis, tumors, ectopic pregnancy, macroamylasemia **Amylase** and **slightly** with **lipase**: biliary disease, renal failure **Amylase and lipase**: pancreatitis, intestinal **obstruction**, **ulceration**, **ischemia**, **perforated viscus**

Answer 85

**Mostly mild** **Some severe** Few get organ failure or infection --\> **death**

Answer 86

Bedside assessment underestimates severe disease Scoring systems: Ranson, Glasgow, Apache, Rabanek Serum markers: trypsinogen activating peptide (TAP), C-reactive protein (CRP), cytokines **CT** criteria: **fluid** collections, **necrosis** **Early** **indicators** of severity: tachycardia, hypotension, tachypnea, hypoxemia, hemoconcentration, oliguria, mental status changes (encephalopathy) **Gray-Turner sign**: bruising in flank due to **retroperitoneal bleeding**

Answer 87

**Admission**: age \>55, WBC \>16K/mm3, Glu \>200, LDH \>350, AST \>120 **After 48 hours**: Hct decrease \>10%, BUN increase \>5, Ca2+ \<8, PaO2 \<60, base deficit \>4, negative fluid balance \>6L

Answer 88

**Supportive** **care**: aggressive fluid and electrolyte replacement, monitoring (vital signs, urine output, oxygen saturation, pain), analgesics, antiemetics Other treatments: **acid suppression**, **antibiotics**, **NG tube**, nutritional support, urgent **ERCP**

Answer 89

Local: **fluid** collections (common, usually resolve spontaneously but drain if infected or symptomatic), **necrosis**, **infection**, **ascites**, **erosion** into structures, GI **obstruction**, **hemorrhage** Systemic: pulmonary, renal CNS, **multiorgan failure** Metabolic: **hypocalcemia, hyperglycemia**

Answer 90

If **sterile**: **medical** **therapy**, debridement for persistent organ failure If **infected**: antibiotics, debridement

Answer 91

Localized mature fluid collections **\>4 weeks after** disease onset Ductal disruption or previous necrosis **Not lined by epithelium** (by definition) **Complications**: pain, GI obstruction, infection, erosion, bleeding, rupture Treatment: endocsopically **drain** into the stomach (external drainage not successful)

Answer 92

Infected **necrosis**: 1-3 weeks; **sepsis**, **multiorgan failure** **Abscess** or infected pseudocyst: \>4 weeks; **fever**, abdominal **pain**, **bacteremia**

Answer 93

**Serous** cystic tumor **Mucinous** cystic neoplasm Intraductal papillary mucinous neoplasm (**IPMN**): associated with pancreatitis **Solid pseudopapillary** neoplasm Note: pseudocyst is always in your differential for these conditions

Answer 94

**Pain, calcification, pancreatic insufficiency**, malabsorption, DM Histology: **calcifications**, **fibrosis**, **inflammation** Causes: **alcoholic**, idiopathic, cystic fibrosis, hereditary pancreatitis, hypertriglyceridemia, autoimmne, fibrocalcific (note: biliary tract disease does NOT progress to chronic pancreatitis) Pathological mechanism: **intraductal plugging** and obstruction, direct toxins and **toxic metabolites**, oxidative stress (**ROS**), **necrosis/fibrosis** (gets worse as you cycle through phases of acute pancreatitis)

Answer 95

**Pain**: intermittent or constant, moderate to severe, **epigastric with radiation to the back** **Steatorrhea**: visible oil droplets or grease in stool (increased volume, light color, foul odor)

Answer 96

Diet and exogenous enzymes: **modify fat intake**, medium chain TGs, **enzyme replacement** Vitamins, supplements: **fat soluble vitamins**, Ca2+, cyanocobalamin (**B12**)

Answer 97

No alcohol (low/moderate effectiveness) **Analgesia** (moderate) Enzyme replacement (low) Neurolytic therapy (moderate short-term) **Pseudocyst drainage** (high) Duct decompression (moderate) Stone removal (controversial)

Answer 98

Control pain Exocrine insufficiency Endocrine insufficiency Quality of life

Answer 99

3-15 fold increase in **cancer risk** with **chronic pancreatitis** **Symptoms** suggesting cancer: **changing** **pain** pattern, weight loss unresponsive to enzyme replacements, development of biliary and/or gastric outlet **obstruction**, new onset of **depression**, migratory thrombosis (**Trousseau's** **syndrome**)

Answer 100

RNA virus (picorna) Fecal-oral Ig is protective **globulin** **Vaccine** against all HAV strains (HAVRIX, VAQTA) Can give immune globulin pre-exposure or **14 days post-exposure** for treatment Diagnose by seeing anti-HAV IgM and past infection/lifelong immunity if see anti-HAV IgG Get HAV **viremia** after infection, then HAV in **stool** **Don't do nucleic acid test** for Hep A because it is self-limiting!

Answer 101

DNA virus Transmitted via **blood/body fluids**, percutaneous/permucosal **HBIG** **Vaccine**

Answer 102

RNA virus (flavivirus) Transmitted via **blood/body fluids**, percutaneous/permucosal (mostly transmitted from **IVDU**) **No protective globulin, no vaccine**

Answer 103

High: **blood, serum,** wound, exudates Moderate: semen, vaginal fluid, saliva Low: urine, feces, sweat, tears, breast milk

Answer 104

**Immune tolerant**: if baby gets infected by mother is immune tolerant for first 2 decades; high HBV DNA but low ALT because minimal inflammation **Immune activation**: immune system "wakes up" and recognizes Hep B virus and attacks hepatocytes so ALT increases and have active inflammation **Low replicative**: have anti-HBe+ and low inflammation, so still HBsAg+ obvi, but just less inflammation so low ALT **Reactivation**: lymphocytes become active again, kill hepatocytes and increase ALT because active inflammation **Remission**: in some lucky people, HBsAg disappears and is inactive so call these patients in remission

Answer 105

**Child**: 95% become **immune tolerant** but then develop **chronic Hep B** **Adult**: 95% **recover** from infection; 5% develop chronic Hep B; note that adults **don't go through immune tolerant** phase (didn't get it as a baby)

Answer 106

Hep B immune globulin (**HBIG**): **infants** born to HBsAg+ mothers (within 12 hours of birth), **sexual** exposure (within 2 weeks of exposure), **needlestick** or mucous membrane exposure, **travel** to areas of high endemicity for HBV, post **liver transplant** in someone with Hep B who has damaged liver from acute liver failure or HCC (give HBIG before and after liver out, then after new liver in, then weekly and monthly to prevent new liver from getting Hep B infection) **Hep B vaccines**: **recombivax** HB, **Engerix** B, **Twinrix** (HAV and HBV): **infants** born to HBsAg+ mothers, **Family members** of HBsAg+ patients, **universal** vaccination for kids, **health care** workers, **MSM/IV drug users**, **travel** to endemic areas

Answer 107

Long-term goals of therapy: prevent clinical outcomes such as death from **liver disease** and development of **HCC** Treatment endpoints: **normalize ALT**, suppress HBV DNA, HbeAg loss and seroconversion to **anti-HBe**, improve liver histology

Answer 108

Immunomodulators: interferon alpha2b (intron A), **Peg IFN** alpha2a (Pegasys) Chain terminator: lamivudine (Epivir HBV), adefovir dipivoxil (Hepsera), **entecavir** (Baraclude), telbivudine (Tyzeka), **tenofovir** (Viread)

Answer 109

**Hep C!** Note: over 1/3 of patients waiting for liver transplants are infected with HCV

Answer 110

15-25% recover from acute Hep C infection (anti-HCV+, HCV RNA-) **75-85% develop chronic Hep C** (anti-HCV+, HCV RNA+, remember that there is NO HCV IgM test to test for infection) --\> after 20-30 years, develop **cirrhosis** or **HCC**

Answer 111

Direct acting antiviral agents (**DAA**): **protease inhibitors** (telaprevir, boceprevir) Recombinant **interferon**: **pegylated** interferon (alpha2a, alpha2b) **Ribavirin**: oral **nucleoside** **analog** Current treatment: **DAAs + pegylated interferon + ribavirin** (highest percentage of patients being SVR)

Answer 112

**Eliminate HCV RNA** **Normalize** serum AST and ALT **Decrease inflammation** and stop/slow progression of **fibrosis** **Improve clinical symptoms** Stop/slow progression to **HCC**

Answer 113

**Null responder**: less than 2-log reduction in HCV RNA **Partial responder**: greater than 2-log reduction in HCV RNA but doesn't get down to undetectable levels, and once take off treatment, HCV RNA increases again **Relapser**: HCV RNA undetectable at end of treatment but goes up again once taken off treatment **Sustained virologic response** (**SVR**): HCV RNA undetectable **6 months** after stopping treatment

Answer 114

Mechanism of action: anti-viral (**interferes with RNA and protein synthesis**), immunomodulatory (increases ability of immune system (WBCs) to **recognize and clear virus**), **anti-proliferative** (BM suppression) IFNs produced by recombinant DNA technology

Answer 115

Synthetic **nucleoside analogue** Ribavirin **alone is ineffective** for treating HCV Effective when **combined with interferon**

Answer 116

Protease inhibitor drugs we use **target NS3** NS3 is the main viral serine protease: **cuts the Hep C polyprotein** to release proteins involved in **viral synthesis** **Inhibiting NS3** prevents cleavage of polyprotein so now proteins **needed for viral replication** **and** **synthesis not available**!

Answer 117

Give **HBIG** and **Hep B vaccine** within 12 hours of birth If you do this, will **prevent Hep B infection 90% of the time**! If mother has **very high viral load** (more than 10^8, more likely that baby will "break through" HBIG and get Hep B--that 10% that do get Hep B infection) Note: even if mother is HBeAg+ (highly infective), HBIG will help prevent Hep B infection!

Answer 118

This antibody is an antibody to hep C virus, but is **NOT protective** against virus! Is made against a recombinant antigen to Hep C but we don't know what it is This is why we **don't have Ig for Hep C**

Answer 119

**7 different genotypes** of Hep C In the USA, **genotype 1** is most prevalent, but is different in different countries Knowing genotype is helpful for **predicting duration of treatment** and **response to anti-viral therapy**

Answer 120

Failure of normal amounts of **bile** to reach the **duodenum** Liver produces bile but gall bladder stores/pushes it out into duodenum Cholestasis if hepatocytes have already created bile and put it out **into canaliculi**, but then there's a **problem**! May cause jaundice (but not all jaundice is cholestatic of course!)

Answer 121

1) Spleen breaks down RBCs/**heme** to produce **biliverdin** then **unconjugated bilirubin** 2) Unconjugated bilirubin binds **albumin** in the blood and goes to liver 3) Liver uses **UGT** to **conjugate** **bilirubin** 4) Liver secretes conjugated bilirubin through bile duct into **duodenum** 5) In the intestine, bacteria create **urobilogen** to be excreted in urine and **stercobilin** to be excreted in feces Note: need conjugated bilirubin to get into gut in order to make stercobilin to color the feces, but DON'T need it to get into gut in order to get color of urine (conjugated bilirubin itself can leak into blood from damaged hepatocytes and cause dark colored urine!!!)

Answer 122

If **pre-hepatic** problem, increased **unconjugated** bilirubin (hemolysis) If **hepatic** problem, increased **conjugated** (and unconjugated) bilirubin If **cholestatic** problem (bile unable to **reach** duodenum for any reason), increased **conjugated** (and unconjugated) bilirubin

Answer 123

Increased **UB** **Hemolysis** (intra or extravascular) Decreased bilirubin uptake (shunts, CHF, **Gilbert's syndrome**) Decreased bilirubin conjugation (**Crigler-Najjar** I & II) Less apparent, no itching, normal color urine (because conjugated bilirubin is NOT leaking into the blood to color the urine dark) Increased **unconjugated** **bilirubin**, increased LDH, reticulocytes, normal AST and ALT, decreased haptoglobin Fragmented RBCs

Answer 124

Increased **CB and UB** Decreased excretion (**Dubin-Johnson**, **rotor**) Hepatocellular injury (**hepatitis**, **cirrhosis**, Wilson's, drugs, **sepsis** (bacteria secrete toxins that block excretion of bile into canaliculi), **postop** jaundice) Apparent jaundice, **dark urine** (because conjugated bilirubin leaking out of hepatocytes, into blood and intoo urine), signs and symptoms of liver disease Increased **ALT and AST**

Answer 125

Increased **CB and UB?** Anything that can cause cholestasis: **PBC**, **PSC**, common bile duct **stone**, **neoplasia**, **strictures**, HIV, PFIC I/II/III, parasites, systemic, medications, TPN **Pruritus**, steatorrhea (decreased bile to absorb fat!) Increased bili, alk phos, AST, ALT, cholesterol, bile acids Vitamin K, A, D, E malabsorption

Answer 126

**Intrahepatic**: alteration of patterns of secretion of bile by hepatocytes; obstruction of intrahepatic bile ducts **Extrahepatic**: obstruction of extrahepatic bile ducts

Answer 127

Genetic: **alpha 1 antitrypsin** deficiency, benign recurrent intrahepatic cholestasis, Byler syndrome, cholestasis of **pregnancy**, abnormal bile acid synthesis, porphyrias Acquired: **medications**, cholestatic hepatitis, bacterial infections, TPN, paraneoplastic cholestasis, postop cholestasis, misc

Answer 128

Primary biliary cirrhosis (**PBC**) Space occupying lesions: primary or metastatic liver **cancer**, lymphoma, amyloidosis **Vanishing** bile duct syndrome: allograft rejection, GVHD, Alagille's syndrome, idiopathic adult ductopenia, **PSC**, Hodgkin's disease, augmentin **Cystic fibrosis**

Answer 129

**Common bile duct stone** Pancreatic **cancer** Ampullary cancer **Cholangiocarcinoma** (cancer of the bile duct) Benign **strictures** Parasites **PSC** HIV cholangiopathy Lymphoma Choledocal cyst BIliary atresia

Answer 130

Generalized, constant or intermittent, exacerbated at night or during warm weather Distressing, and has lead to suicide Pathogenesis controversial **Bile acids theory**: increased bile acids in skin and blood, bile acid-binding resin/sequestrant (**cholestyramine**) is effective; however probably **not correct** because no correlation between bile acids in skin and itching **Opioid receptors theory**: opiates induce facial scratching in animals, endogenous **opioids accumulate** in cholestasis, plasma extracts induce facial scratching in monkeys, opioid antagonists relieve pruritus Common symptom with cholestasis?

Answer 131

**Decreased bile acid** concentration in intestine --\> **impaired micelle** formation --\> inadequate fat solubilization --\> **malabsorption** of dietary fats

Answer 132

Malabsorption of dietary fats --\> **fat soluble vitamin malabsorption** Vitamin A: **night blindness** Vitamin D: **bone disease** Vitamin E: **cerebellar ataxia**, **peripheral neuropathy,** retinal degeneration (in kids) Vitamin K: **coagulopathy**

Answer 133

Due to **hypercholesterolemia** Resolve after relieving the obstruction

Answer 134

**Osteopenia** and **osteoporosis** Multifactorial: vitamin D (but NOT due to deficiency in vitamin D or Ca2+), calcitonin, hormonal factors, immobility, reduced muscle mass Prevalence: 30-50% Fractures: 7-10% **Improves after OLT**

Answer 135

From **longstanding obstruction** (can be only a few **months**) Complications of portal HTN are very common Hepatocellular carcinoma is rare

Answer 136

**Hyperbilirubinemia** Increased **alkaline phosphatase** Increased **5' nucleotidase** (specific for liver, so if this is elevated, tells you alk phos **IS because of liver!**) Increased **ALT and AST** Increased **bile acids** Increased **cholesterol** Increased copper

Answer 137

Drugs: **cholestyramine** (sequesters bile acids), ursodiol (makes bile soluble to be secreted into canaliculi), antihistamines (just put pt to sleep!), rifampin, phenobarbital, opioids If drugs don't work/**severe** cases: **plasmapheresis**/hemoperfusion is **transiently** effective **Phototherapy** is beneficial in anecdotal reports **OLT is indicated** when **pruritis** associated with chronic liver disease, is **refractory** and is impacting quality of life

Answer 138

Adequate **caloric intake** 30-40g **fat** per day **Medium chain TGs** **Ca2+** supplements Parenteral **vitamin K** (no bile so no absorption of vitamin K in gut) Document and replace vitamins A, D, E

Answer 139

Bone densitometry Correct **vitamin D** deficiency **Ca2+** supplements **Biphosphonates** (alendronate) Calcitonin and fluoride (experimental) HRT Prevention through **physical exercise**, avoid steroids

Answer 140

**Relieve** the obstruction (ERCP, PTC, surgery) Treat the **underlying** **condition**

Answer 141

If greater increase in **ALT and AST**: do viral serologies, ANA, SMA, tox screen, ceruloplasmin --\> then maybe liver biopsy to look for cause of **hepatitis**, inflammation If greater increase in **alk phos**: if no biliary duct dilation, do liver biopsy to look for **intrahepatic cholestasis**; if dilated ducts (on ultrasound), do CT/ERCP to look for **obstruction**

Answer 142

NASH is a **subset** of NAFLD Prevalence of NAFLD around 24%; prevalence of NASH is 6.3% NAFLD is a spectrum: **fat** (which can cause benign fatty liver) --\> **fat with inflammation** (which can turn into NASH) --\> **cirrhosis** (which can turn into HCC)

Answer 143

**Inflammatory** **response** against **neoantigens** placed in lipid-laden hepatocytes

Answer 144

NAFLD is most **common** liver disorder in world and most common etiology of increased LFT in the US Diagnosis: **fatty infiltration** of the liver, non-alcoholic Steatosis in 70% of obese people and even 35% of lean people Presents in 30-50s **Familial** clustering (no genetic marker though) In hispanics and blacks, M:F same but in whites, males affected more than females

Answer 145

**Waist to hip ratio** (\>0.9) but NOT BMI

Answer 146

**Metabolic:** obesity, **diabetes** (glucose intolerance, insulin resistance, hyperinsulinemia)**, hyperlipidemia** (cholesterol or TGs), rapid weight loss, TPN, acute starvation Inborn errors of metabolism: Wilson's disease, abetalipoproteinemia, tyrosinemia, hypobetalipoproteinemia **Surgical procedures**: jejuno-ileal bypass, biliopancreatic diversion, extensive small bowel resection, gastroplasty for morbid obesity Drugs/toxins: **amiodarone**, glucocorticoids, perhexiline maleate, synthetic estrogens, tamoxifen, diltazon, DHEAH, **HAART**, isoniazid, industrial exposure to petrochemicals Misc: partial lipodystrophy, jejunal diverticulosis with bacterial overgrowth

Answer 147

**Insulin resistance DM** **Hyperlipidemia** **Hypertension** **Truncal obesity** **NAFLD**

Answer 148

Obesity, genetics, environment, diet and activity --\> increased lipolysis --\> **increased** **FFA** --\> decreased metabolic clearance of glucose by the muscle and increased hepatic glucose output --\> **increased glucose load** --\> **hyperinsulinemia** --\> pancreas works really hard until it quits and you develop diabetes

Answer 149

Uncoupled oxidation and phosphorylation 1) Increased **ROS** 2) Decreased **antioxidants** **Increased** **oxidative stress** within the hepatocytes causes progression from NAFLD to NASH

Answer 150

Common: **asymptomatic** (48-100%), hepatomegaly, **2-4 fold elevation of ALT and AST**, AST/ALT\<1 in most cases, alk phos elevated in 1/3, elevated serum ferritin (53-62%) Uncommon: vague RUQ pain, fatigue, malaise, splenomegaly, spider angiomata, palmar erythema, ascited, low titer ANA, elevated transferrin saturation, Cys282Tyr mutation of HFE

Answer 151

Most (59%) remain **stable** 13% improve 28% progress to cirrhosis This is not fully understood though

Answer 152

Note: all studies bad, no good evidence for these treatments **Weight reduction** (probs no benefit!) Lipid lowering agents (clofibrate, atorvastatin, gemfibrozil) or urodeoxycholic acid but no evidence to use these medications because studies bad quality **Vitamin E** Antioxidants Metformin Orlistat Rimonabant: endocannabinoid type 1 receptor blocker Thiazolidinedions (-glitazones): have side effects, so don't want to use in someone who just has fatty liver (vitamin E better too!) **Coffee!!**

Answer 153

**Restrictive**: vertical gastroplasty, lap band, roux en Y gastric bypass **Malabsorptive**: jejunal ileal bypass, gastric diversion (these more likely to cause liver diseases) In general, getting WLS decreases death from MI, cancer, diabetes, heart disease

Answer 154

**Weight loss** Histologic improvement (91%) Improvement of **liver tests** Improvement in metabolic syndrome

Answer 155

**Decreased BMI** Decreased metabolic syndrome Decreased **LFTs** Histologic improvement (89%)

Answer 156

**Surgery** to do before patient gets liver transplant to **control metabolic syndrome, DM, HTN** to have less complications and shorter hospital stay

Answer 157

**Worse response to ischemic injury** (less ATP, less ability to regenerate, **necrosis** instead of apoptosis for cell death) Also if graft/tx fatty liver into a patient, they will have **lower survival** and **Hep C will recur** more often

Answer 158

**Exercise** Control weight Eat well-balanced diet Control your DM and HTN Avoid alcohol Decrease fructose intake (high calorie) **Vitamin E** (controversial) Early steroid taper **Bariatric surgery** (BMI\>40 with failed diet and exercise)

Answer 159

Probably a **genetic defect** in liver repair mechanism

Answer 160

Chronic injury over **years** (not trauma or single acute insult like acetaminophen OD): **Hep C** **Alcohol** **Obesity** Insults may be synergistic Usually more than 1 things causing cirrhosis Also: NASH, Hep B, autoimmune, chemicals, drugs, Wilson's, hemochromatosis, alpha1-antitrypsin deficiency

Answer 161

**Compensated**: maybe unaware that they have cirrhosis, asymptomatic **Decompensated**: ascites, hepatic encephalopathy, variceal bleeding

Answer 162

**Ascites** 47% **Encephalopathy** 28% **Gut bleeding** 25%

Answer 163

**Liver biopsy** is gold standard Transjugular biopsy possible **Clinical diagnosis** may be okay, and is **common** (history, physical, labs, imaging)

Answer 164

**Silent** (seen at autopsy or in OR) Fatigue Weight loss Stigmata: **vascular spider angioma** (blanches; not seen below umbilicus), palmar erythema, abdominal wall collaterals PE: palpable liver and/or spleen, ascites, asterixis Labs: **low platelets** (\<160,000), high INR, abnormal AST, ALT, bilirubin, low albumin, low BUN

Answer 165

Low platelets (**thrombocytopenia**) in cirrhosis can be mistaken for immune thrombocytopenia (ITP) Hypersplenism (esp in Hep C) **Low thrombopoeitin** Anti-platelet **antibodies** **Sequestration** of platelets in **liver** and **spleen**

Answer 166

**No** prophylactic **protein** or **Na+ restriction** Achieve BMI 20-25 **No alcohol** (0% of active drinkers alive after 3 years) **Avoid excess vitamin A** Aboid herbals except **vitamin D**, which you should supplement! Target vitamin D \>30

Answer 167

**Acetaminophen** (Tylenol) is actually fine (\<4000mg/d is ok!) Tramadol okay if acetaminophen isn't strong enough **NO NSAIDs!** Trazodone or hydroxyzine for insomnia (not benzos bc cause coma) Minimize narcotics

Answer 168

**Model for End Stage Liver Disease** (MELD): INR, total bilirubin, creatinine UNOS organ allocation Repeatedly validated for **predicting survival** Low means better prognosis, high means bad and you'll get a transplant (\>16 to benefit from transplant)

Answer 169

**Never** if you don't have to--only for a liver transplant!

Answer 170

GABA agonist that is an anti-spasmodic Also used to **reduce alcohol cravings!**

Answer 171

High pressure in portal vein due to **resistance** in liver from **scarring** Classified as **12mmHg** or higher (hepatic vein-portal vein gradient is normally \<4mmHg) Can lead to **esophageal varices** (that can rupture) and **ascites** (abd swelling, foot edema, shifting dullness)

Answer 172

85% due to **cirrhosis** **Paracentesis** despite coagulopathy (even if high INR and low platelets!) to do cell count and differential, SAAG (**serum-ascites albumin gradient** is **\>1.1 g/dL** in liver ascites because liver ascites fluid has LOW albumin (gradient less when ascites due to peritoneal fluid because that has high protein!)), ultrasound Consider transplant referral Treatment: **Na+ restricted** diet (2g per day), NO protein restriction, oral **diuretics** every morning (spironolactone, furosemide), no NSAIDs or nephrotoxic meds Diet and dual diuretics 90% effective, but for 10% refractory ascites do liver transplant, large vol paracenteses q 2 weeks, transjugular intrahepatic portosystemic stent-shunt (TIPS; shunt between portal and systemic circulations (within the liver!)), peritoneovenous shunt Propanolol and ascites??

Answer 173

Functional **renal failure** Type I: precipitated by infection, GIB, etc; treat with IV albumin, octreotide, midodrine Type II: mode of exitus in terminal liver failure; treat with liver transplant

Answer 174

**Second** most common **complication** (28% over 10 years) of cirrhosis Transient, reversible **confusion**, drowsiness **Asterixis**, trail test, DON'T use ammonia to dx because no correlation with symptoms Precipitating factors: **dehydration**, **infection**, **GI bleed**, narcotics, benzos, hypokalemia Treatment: **lactulose**, **rifaximin** (or neomycin), no protein restriction

Answer 175

Third most common **complication** (25% within 10 years) of cirrhosis Usually esophageal varices bleed (occasionally gastric or ectopic varices) Heavy **lifting** or **NSAIDs** can precipitate bleeding Best prevention for esophageal varices is **propanalol** To treat variceal hemorrhage, give **octreotide** (vasoconstrict) IV, packed **RBCs**, **FFP**, **ceftriaxone**/norfloxacin; endoscopic **ligation** (better than sclerotherapy), **banding**, rarely balloon tube, shunt/**TIPS** for refractory

Answer 176

CYP3A **inhibitors** (higher drug conc): azole antifungals, macrolides (clarithromycin, erythromycin, NOT azithromycin), cimetidine, grapefruit juice CYP3A **inducers** (lower drug conc): rifampin, rifabutin, carbamazepine, ritonavir, St. John's wort

Answer 177

Major reason for **drug withdrawal** from market \>50% of **acute liver failure** cases due to drugs (**acetaminophen** accounts for half of these) **Idiosyncratic drug reactions** result in OLT or death 75% of the time We don't detect DILI more often because liver injury is infrequent

Answer 178

10% of DILI develop jaundice, and 10% of those die So, **1% chance of death from ADR**

Answer 179

Note: not called fulminant hepatic failure anymore Coagulopathy (INR \>1.5) and any encephalopathy in a **non-cirrhotic** patient within period of **6 months** In clinical scenario we say if you become jaundiced and have hepatic encephalopathy within 6 weeks, would be ALF

Answer 180

**N-acetylcysteine** (NAC) regenerates **GSH** (is a glutathione precursor) and buffers NAPQI to non-toxic metabolites if given promptly after APAP overdose Use the Rumack-Matthew line using hours post-ingestion and APAP plasma concentration to determine who should/should not get NAC (the antidote) No serious side effects of NAC!

Answer 181

1) Causes **blebbing** of hepatocyte membrane --\> damage 2) Impeded **bile** **flow** --\> cholestasis 3) Aberrant **drug metabolism**: slow vs. rapid acetylators, diff genotypes for CYP enzymes 4) **Immune-mediated** mechanisms of liver cell death 5) Leaking of **mitochondria** so mess up ability to do beta oxidation of fatty acids and respiratory chain (common in NASH) 6) Induce **apoptosis**

Answer 182

**Hepatocellular**: high **ALT** and **AST** but not as high alk phos, N/A/V, upper abdominal pain, onset within a few days and **resolves** **faster**, zone 3 necrosis, eosinophils, granulomas, steatohepatitis; this kind is more likely to **kill** **you** **Cholestatic**: jaundice, itchy, severe nausea, high **bilirubin** and **alk phos**, cholestasis without cholangitis and no features of biliary obstruction Remember that DILI is in differential for any LFT abnormality

Answer 183

Drugs start damage around **portal tract** (this is where they come in) whereas fatty liver damage begins around central veins

Answer 184

**Triglitazone**: apoptosis, fluffy cells **TMP-SMX**: obliteration of bile ducts and inflammatory infiltrate **Isoniazid**: apoptosis, lakes of bile because of cholestasis **Augmentin** (amoxicillin-clavulanic acid): apoptosis and larger lakes of bile pools **Phenytoin**: immunoallergic features (eosinophils), necrosis/death around portal triad **Diltiazem** (and other Ca2+ channel blockers): granulomatous hepatitis **Tamoxifen**: steatohepatitis **Didanosine** in HIV: microvesicular steatosis because inhibits beta-oxidation of fatty acids and damages mitochondria **Acetominophen**: liver destruction..? **Methotrexate** and **Vitamin** **A**: fibrosis **Chemo** agents: venoocclusive disease (rare, shows up after BM transplant and this is why treat BM tx pts with ursodiol) **Estrogen, androgens, MTX, aflatoxins, carbon tetrachloride**: hepatic neoplasms

Answer 185

**Reduced hepatic flow**/portosystemic shunting: low 1st pass extraction, higher serum levels and bioavailability **Hypoalbuminemia**: less protein binding --\> increased serum concentration **Ascites**/edema: increased vol of distribution for hydrophilic drugs **Portal gastropathy**: altered drug absorption (either increased or decreased) **Loss of CYP450 activity**: reduced clearance I**mpaired biliary transport** and/or **renal excretio**n: increased serum concentration Dose reductions in cirrhosis are recommended but no concrete evidence that CYP450 system doesn't work as well in someone with normal liver

Answer 186

News says that **milk thistle** was good for treating **Hep C**, but wasn't (no effect on ALT, HCV viral levels) People now take milk thistle for Hep C, Hep B, NASH and say it **subjectively** improves fatigue, anorexia, nausea, general well-being, even though **no evidence**; also because people just like to take medicine

Answer 187

Acute liver failure: Hep A, Hep B, Wilson's disease HCC (and cirrhosis): hemochromatosis, steatohepatitis (NASH), Hep B, alpha1-antitrypsin deficiency,

Week 7 (Hepatobiliary) Flashcards

(211 cards)