Block 1: Pancreas, Hepatobiliary, and Liver Disorders Flashcards
What are the functions of the liver?
- Produces bule
- Synthesizes plasma proteins
- Metabolize and eliminates drugs and toxins
- Stores vitamin, glucose, and blood
What is hepatomegaly?
Abnormally enlarged liver
Where is the liver located?
right upper quadrant
What are the structural units that contain hepatocytes?
Liver lobule
What are hepatocytes?
Specialized cells of liver that produce enzymes that catalyze various chemical reactions
What are sinusoids?
Capillaries of liver lobule located between hepatocytes, receives blood from hepatic artery and portal vein and remove foreign materials from blood
Why does hepatic differ from standard blood supply?
75% from vein
25% from artery
What is the difference between hepatic artery and vein?
Artery: brings oxygen rich blood from abdominal aorta
Vein: Brings nutrient rich blood from digestive system
What are the types of hepatic portal vein?
- Superior mesenteric: brings blood from small intestine, ascending and transverse of large intestine and stomach
- Splenic vein: brings blood from spleen and pancrease
- Inferior mesenteric vein: collects blood from descending region of large intestine and rectum
- Central vein: move blood out of liver to heart
What are the Kupffer cells?
Phagocytic cells lining sinusoids that remove bacterial and foreign materials from blood
What clotting factors are synthesized by the liver?
I, II, VII, IX, X
What proteins are synthesized by the liver?
Albumin, globulin
What is bile?
Yellow-green thick fluid that breaks fat into small globules
What is bilirubin?
Brownish-yellow substance produced when liver breaks down red blood cells
What is biliverdin?
Pigment that gives bile its greenish color
Where does bile go once leaving the hepatic duct?
- Stored and concentrated in gallbladder
- Released via common bile duct to duodenum
What hormone produces bile?
Secretin from the duodenum
What is the process of excretion?
Bilirubin secreted and transported to feces
Liver breakdowns and detoxifies substances
What are the downside of hepatic detox?
Damages to hepatocytes
What is checked in a liver function test?
- Albumin
- Bilirubin
- AST
- ALT
- GGT
- Prothrombin
What happens when liver damage prevent albumin production?
- Causes body fluid leaks to interstitial spaces and peritoneal cavity
- Caused by edema, ascites
What happens when liver damage prevent ammonia conversion?
Ammoniamo accumulates → systemic damage
How do we test for liver disorders?
Bilirubin levels: Indicator of liver and pancreatic dysfunction
Elevated pancreatic pancreatic amylase and lipase
What is jaundice?
Yellowish discoloration of whites of eyes, skin, or mucous membranes caused by bile salts in tissues
What gives feces its dark color?
Bilirubin
What is amylase?
Breaks down starch to disaccharides
What is lipase?
Fat digestion to produce fatty acids and glycerol from triglycerides
What causes jaundice in newborns?
Takes several days to produce enzyme needed for conjugation of bilirubin (glucoronyltransferase)
What is cause of cirrhosis?
- Alcohol consumption → alcoholic liver disease → alcoholic hepatitis → hepatocellular damage, inflammation, obstruction → damages in hepatocytes and surrounding tissue
- Replacement of hepatocytes with scar tissue
- Constriction of blood and bile flow
- Enlarged spleen damages → leukopenia, anemia, thrombocytopenia
Cirrhosis rates are higher in ___?
Males
What is a fatty liver?
Alcohol catalyzes enzymes → enzymes make fatty acids → fatty acid accumulates in liver as fat → steatosis (early stage)
What system is used by the liver when consuming large amounts of alcohol?
Microsomal ethanol-oxidizing system → fatty deposits and TG
What are causes of liver blood flow constriction?
Portal hypertension forces blood out of the liver→ shunts blood to spleen → splenomegaly
How does ascites from portal HTN cause dyspnea?
- Increased abdominal fluid place pressure on diaphragm
- Difficulty breathing
- Swollen abdomen
What are the factors that increase the severity of cirrhosis?
- Pattern of drinking
- Amount of alcohol
- Number of years drinking
- Liver damaging
How can you fix progression of cirrhosis from alcohol?
Elimination of alcohol can repair damages
What leads to irreversible liver damage from alcohol?
Liver shrinks and takes on nodular appearance → liver failure that is irreversible
What delays liver damage diagnosis?
- Vascular and regenerative capacities of liver
- Deep location of liver in abdominal cavity
What are the sx in patients with steatosis?
1, Asymptomatic
2. Elevated LFT
3. Palpitation
4. RUQ discomfort
Continual drinkers may experience what kind of sx?
- N/W
- Anorexia
- Weight loss
- Jaundice and icterus
What are the labs associated with metabolic liver disease?
Damage to hepatocytes
Prolonged prothrombin time
Portal HTN shifts fluids to body compartment
How can hypoalbumnemia and hyperaldosteronism contribute to ascites?
Hypoalbumnemia: loss of colloid osmotic pressure
Hyperaldosteronism: retention of sodium and water to elevate blood pressure
Sx of increased cerebral edema?
- Confusion
- Disorientation
- Decreased cognition
What builds up do to dysfunctional liver metabolism?
Ammonia and unmetabolized medications → toxicity
What is gynecomastia?
Inability of liver to degrade estrogens in males from phytoestrogens in alcohol → breast enlargement from testosterone and estrogen imbalances
What are signs of further liver failure from portal HTN?
- Asterixis
- Spider angioma
- Caput medusa
- Esophageal varices
What is asterixis?
Muscle tremor causing downward flap of hand when arm is extended
What is spider angioma?
Dilated arteriole seen as small red dot with tiny, fragile veins surrounding the skin’s surface caused by unmetabolized estrogen
What is caput medusa?
Bluish veins under the skin that radiate out across umbilicus → ascites and abdominal pressure
What is esophageal varices?
Swollen esophageal veins → increased pressure in vessels due to portal HTN from liver scarring
How many lobes are there in the liver?
2
What does normal liver function look like?
Dual blood supply from hepatic artery and portal vein
Hepatic vein moves blood to heart
What is classification of liver failure? Leading cause?
80-90% of hepatic function must be compromised
- Excessive alcohol
- Hepatitis C virus
What is acute liver failure?
- Elevated liver test due to inflammation
- Prolong coagulation time
- Mental state alterations
What is cirrhosis?
Scarring of the liver associated with poor liver function → systemic changes due to portal HTN
What are the complications of chronic liver failure?
- Portal hypertension
- Esophageal varices
- Ascites
- Hepatic encephalopathy
What are the complications of acute liver failure?
- Hepatic encephalopathy
- Coagulopathy (decreased clotting factor production)
What is Portal HTN?
Increased portal venous pressure:
Increased resistance to blood flow through the portal venous system and pressure gradient over 5 mmHg
What is the most common cause for cirrhosis?
Portal HTN
What are the non cirrhotic causes of portal HTN?
Prehapatic: portal thrombosis, narrowing of portal veins
Posthepatic: severe right-sided congestive heart failure, hepatic vein outflow obstruction
What are the Problems associated with increasing portal pressure?
- Hyperdynamic circulation
- Esophageal varices and hemorrhage
- Rectal varices
- Splenomegaly
What are the problems associated with systemic circulatory abnormalities or portosystemic shunt?
- Ascites
- Encephalopathy
What is esophageal varices?
Increased portal hypertension → flow through the liver drops → increased pressure in blood vessels lining the esophagus
What are the sx of acute bleeding in esophageal varices?
- Melena
- Hematemesis
- Bright red blood from rectum
What are ascites?
Abnormal collection of excess fluid in the abdominal cavity → poor prognosis
What causes ascites?
Peripheral arterial vasodilation → decreased systemic vascular resistance
How do spontaneous portosystemic shunts cause ascites?
redirection of blood flow and vasodilators → Capillary permeability and lymph formation increase → Ascites develop when the body can not longer absorb this fluid
What are the sx of ascites?
- Increased abdominal girth
- Weight gain
- Bulging flanks
- Shifting dullness
- Decreased appetite
What is icterus?
Yellowing of the sclerae of eyes
What is cholestasis?
Systemic retention of excess bilirubin and other bile solutes
What is the difference between unconjugated and conjugated bilirubin?
Unconjugated: Cannot be excreted in urine because it is tightly bound to albumin and is insoluble in water
Conjugated: Can be excreted in urine because it is loosely bound to albumin and is water soluble; nontoxic
How is bilirubin eliminated from the body?
Extrahepatic bilirubin binds with albumin and is delivered to the liver → glucoronidation in ER → Water-soluble, nontoxic bilirubin glucuronides (direct bilirubin) are excreted in bile → Gut bacteria deconjugate the bilirubin into urobilinogens that are excreted in the feces (stercobilin) and enterohepatic circulation → Some products may be reabsorbed and then excreted in urine
How can Extrahepatic obstructive cholestasis develop?
Obstruction of common bile duct due to tumor, gallstone, or compression
What are signs of bilirubin levels increase?
- Urine becomes tea colored
- Stools become clay colored
- Pruritis occurs.
- Serum alkaline phosphatase levels increase.
- Gamma glutamyl transpeptidase (GGT) levels increase
What are the signs of reduced bile flow?
- Decreases intestinal absorption and leads to deficiencies of fat-soluble vitamins A, D, E, and K
- Fever, chills, and RUQ pain
- Xanthomas
What is alcoholic liver disease?
Damage to the liver and its function due to alcohol abuse
What are the causes of alcoholic liver disease?
- Steatosis: accumulation of lipid droplets in liver cell cytoplasm
- Steatohepatisis: Multifactorial inflammation seen in setting of steatosis
- Ballooning degeneration: swelling of hepatocytes due to severe cell injury
- Mallory body formation: Damaged filaments in the liver that accumulate
- Fibrosis → cirrhosis
Why is alcohol so damaging?
- Affects CYP450 system
- CYP2EI inducer
- Catabolism in the ER increases
- ROS ↑ (lipid per oxidation and acetaldehyde protein adducts, methionine metabolism impaired, glutathione levels ↓
How does alcoholic liver disease ↑ gut permeability?
- Hepatic exposure to gut bacterial degradation releasing endotoxins
- Kupffer cell activate
- Proinflammatory cytokines release
Hepatocellular death occurs due to damage to and disruption of proteins and DNA
Accumulation of cells
What are the labs of alcoholic liver disease?
2:1 ratio of AST/ALT
Leukocytosis
Elevated GGT
What is the physical sx of alcoholic liver disease?
- Hepatomegaly
- Jaundice
- Ascites
- Encephalopathy
- Spider angiomata
What is NAFLD?
Spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) caused by a deposit of lipids in liver
What is the NAFLD spectrum?
Simple steatosis: Mild liver disease, 5% lipid accumulation
NASH: inflammation and hepatocyte damage → cirrhosis
What are the important components of NASH and how is it associated with NAFLD?
Metabolic syndrome
1. Overproduction leads to components of metabolic syndrome: hyperglycemia, DLD, hyperinsulinemia
Insulin resistance:
1. Fatty liver is insulin resistant and overproduces LDL, glucose, CRP, IL6
What are sx of NAFLD?
- Elevation of liver transaminases
- AST higher than ALT levels
- Obesity
- Diabetes
- DLD
What is acute liver failure?
Loss of hepatocyte function affecting almost the entire liver without the presence of cirrhosis
What is the leading cause of acute liver failure?
Drugs (Acetaminophen) → hepatic necrosis
Describe the cell injury of acute liver failure?
- Direct toxic damage
- Combination of toxic damage and immune-related inflammation
What is the treatment for severe acute liver failure ?
liver transplantation
What are the hallmark signs of acute liver failure?
- Coagulopathy
- Altered mental status (encephalopathy)
- Jaundice can occur
- Hepatic coma or cerebral edema
What is Cholelithiasis?
Stone formation in the gallbladder
Why is a gallstone problematic?
Blockade of bile → inflammation and tissue damage
What is a gallstone composed of?
Cholesterol (80%)
Pigment (20%)
→ Caused by excessive cholesterol from obesity and high fat diets
What are the risk factors of Cholelithiasis?
- Femal
- Fair
- Fat
- Fertile
- Forty
What are the sx of Cholelithiasis?
- Nonspecific complaints following consumption of fat: indigestion and mild gastric distress
- midepigastric pain in RUQ, right uubscapular pain, back
- Biliary colic: Painful spasms to RUQ that accompany obstruction in cystic duct by stone.
- Steatorrhea: Greasy, foul-smelling feces containing undigested fats
- Bile salts accumulated in blood
What is the function of the pancreas?
- Digestive enzymes in exocrine cell
- Hormone in endocrine cells
What is acute pancreatitis?
Inflammation or necrosis of the pancreas.
What is the most common form of pancreatitis?
Edematous pancreatitis
What are the causes of pancreatitis?
- Alcohol abuse
- Gallstones
- Virus
- Trauma/surgery
How can gallstones cause pancreatitis?
Trap digestive enzymes (trypsin) → auto digestion og pancreas → inflammation
What does inflammation of acute pancreatitis look like?
- Release of inflammatory mediators → ↑ vascular permeability and vessel dilation
- Leaking of fluid into peritoneal cavity → hypovolemia and decreased renal BF
- Systemic inflammatory response system (SIRS)
- Multiple organ failure (MOF)
What are the sx of acute pancreatitis?
- Pain in upper abdomen
- Deep epigastric pain
- Abdominal dissension and tenderness
- Tachycardia
- Hypotension
- Fever
- Jaundice
- ↑ in amylase/lipase
What is Parethesia?
Prickly pins-and-needles sensation in alcoholics or pernicious anemia
What is cullen sign?
Bruising and edema to subcutaneous tissue from hemorrhagic pancreatitis
What is grey-turner sign?
Bruising in flank area from bleeding behind the peritoneum
What is steatorrhea?
From decreased or absent lipase
What are the main clinical manifestation of acute pancreatitis?
- Parethesia
- Cullen sign
- Grey-turner sign
- Steatorrhea
What are the warning signs of acute pancreatitis progression?
- Low UO
- Hypoxemia
- Restlessness
- Altered mental status
What is chronic pancreatitis?
Tissue damage is irreversible even though chronic pain is less severe
What are the causes of chronic pancreatitis?
- Alcoholism
- Genetics (familial HLD)
What are sx of chronic pancreatitis?
- Weight loss
- Dull, constant abdominal pain
- Remove alcohol consumption
