The Liver and Pancreas

Question 1

functions of the liver

Answer 1

1. Carbohydrate metabolism
2. Protein synthesis (Albumin, globulins, lipoproteins, clotting factors)
3. Lipid metabolism
4. Drugs metabolism
5. Hormone metabolism
6. Bile production: What you make in the liver, you store in the gallbladder – the gallbladder then squeezes its contents and sends it out into the intestine through the sphincter of Odie? - Secreted under hormonal control from the intestines

Question 2

Bilirubin metabolism

Answer 2

• bilirubin we get from blood – give stool its color
• Urobilinogen circulates and goes back to the liver 6-8 times a day
• Entero = intestine
• Hemoglobin we get about 85% of bilirubin
• Myoglobin and cytochromes give us the last 15%
• Biliverdin gives unconjugated bilirubin and albumin
• Red blood cells last 3-4 months
• As they get old and break down, cells in the immune system (macrophages) gobble them up and break them down (Break it down into heme component and bilirubin, That bilirubin circulates in the blood unconjugated and will be absorbed by hepatocytes in liver, The liver conjugates the bilirubin (combines the molecules) and incorporates this into bile)
• When you have a patient that has a bilirubin abnormality (high) you need to ask where this is coming from (Is it high because they’re making so much bili that the liver cant keep up? - Are they bleeding? Are they breaking down blood products at an abnormal rate? Are they creating a lot of the bilirubin)
• Unconjugated means that it hasn’t been managed by the liver yet so if the increased total bilirubin is coming from abnormal amount unconjugated, you know the problem is before the hepatocyte or before the enzymatic process within the hepatocyte (it might be that there’s a problem conjugating or that they are just making a ton of bili)
• Gilbert syndrome – unable to conjugate bili

Question 3

bilirubin testing

Answer 3

• Total – when elevated, does not separate pre-, intra-, post-hepatic causes
• Unconjugated (indirect) – test level of bilirubin prior to liver metabolism (Hasn’t been processed by the liver yet)
• Conjugated (direct) – after liver processing (Already been through the liver, been enzymatically processed, Something is not allowing it to be excreted normally)

Question 4

liver function tests

Answer 4

• things we call “liver function tests” are actually tests of liver health
• Health of the hepatocytes
• They are NOT TESTS OF LIVER FUNCTION!!!!
• Necrosis = cell death
• They are tests of the status and wellbeing of the hepatocytes or damage to them, but not their function
• AFT, ALT = transaminases!
• Necrosis index: they are in the blood when the cells are damaged and therefore spill those enzymes into the blood (If you take a normal dose of Tylenol, these levels will go up)
• Cholestasis index: alkaline phosphatase and GGT
• AST > ALT  THINK ALCOHOLIC LIVER DISEASE

Question 5

cholestasis

Answer 5

• Decrease in bile flow through the intrahepatic canaliculi
• Increase in cholesterol, bilirubin and bile acids in the blood
• Extrahepatic cholestasis and Intrahepatic cholestasis

Question 6

features of cholestasis

Answer 6

• Types: Obstructive and Hepatocellular
• Bile lakes: Intraductal cholestasis
• Bile pigment: Intracellular accumulation
• Fibrosis
• Cirrhosis
• Damage to the hepatocyte itself will cause the problem right next to the hepatocyte: Pregnancy can cause this problem

Question 7

jaundice

Answer 7

• HEMOLYTIC (PREHEPATIC)
• Blood transfusion reactions
• Hereditary red cell disorders
• Acquired hemolytic disorders
• Autoimmune hemolytic anemia
• Hemolytic disease of newborn
• HEPATOCELLULAR (HEPATIC) (Decreased bilirubin uptake, Decreased conjugation, Hepatocellular liver damage, Drug induced)
• OBSTRUCTIVE (POSTHEPATIC) (Cholelithiasis – gallstone, Congenital atresia – bile tree didn’t form properly, Tumors (Cholangiocarcinoma))

Question 8

symptoms of cholestasis

Answer 8

• Pruritis: Plasma bile salts
• Jaundice: conjugated bilirubin
• Skin Xanthoma: hypercholesterolemia
• Alkaline phosphatase: membrane bound enzyme
• Fat –soluble vitamins deficiencies: A/D/E/K

Question 9

hepatitis

Answer 9

• Malaria (plasmodium falciparum)
• Staphylococcal bacteremia
• Salmonellosis
• Candidiasis (disseminated dz in immunocomp’d)
• Amebiasis (100,000 deaths/yr – trohpozooites from ingested cysts infest liver, lung, brain)
• Miliary TB

Question 10

viral hepatitis

Answer 10

• Infectious mononucleosis
• Cytomegalovirus
• Herpes virus
• Yellow fever
• Rubella, adenovirus, enterovirus
• Hepatitis A, B, C, D, E viruses (A and E = fecal oral, BCD = blood borne)
• Acute: self limited, resolving disease
• Fulminant hepatitis: Massive hepatic necrosis
• Chronic: duration greater than 6 months
• Carrier state: Patient has no clinical disease, but has positive serum markers for virus production
• Subclinical infection: Asymptomatic infection or anicteric “flu-like” syndrome usually only noted to be hepatitis by identifying HBsAb at a later date
• Classification of viral hepatitis

Question 11

serology of acute and chronic hepatitis B

Answer 11

• MEMORIZE THIS CHART!!!!!
• You can test for hep B surface antigen – causes the immune response
• YOU MAKE IGM antibodies first!! IMMEDIATE
• IGG are lasting antibodies

Question 12

viral antigens and antibodies

Answer 12

o	HBsAg
o	HBeAG
o	HBV DNA
o	IgG anti-HBc
o	IgM-antiHBc
o	Anti- HBs

Question 13

chronic hepatitis

Answer 13

• Chronic viral hepatitis
• Chronic alcoholism
• Drugs (isoniazide (TB), methyldopa (HTN), methotextrate (immunomodulator))
• Autoimmunity

Question 14

clinical features of chronic hepatitis

Answer 14

o FATIGUE
o MALAISE
o BOUTS OF JAUNDICE
o LOSS OF APPETITE

Question 15

laboratory features of chronic hepatitis

Answer 15

• Increased prothrombin time
• Hyperbilirubinemia
• Mild elevation in alkaline phosphatase
• Elevation of serum transaminases depends on the degree of damage
• Hepatocytes have to be damaged and spilling enzymes into the blood to see AST or ALT go up

Question 16

intrahepatic biliary disorders

Answer 16

-Primary biliary cirrhosis – cirrhosis of the biliary tree – moreso in females

Question 17

alcohol induced liver disease

Answer 17

• Steatosis (Fatty change)
• Hepatitis (Jaundice, Tender liver, pain, anorexia, ascitis, fever)
• Cirrhosis

Question 18

cirrhosis

Answer 18

• End stage of chronic liver disease
• Regenerative nodules
• Micronodular or macronodular

Question 19

causes of cirrhosis

Answer 19

o Alcoholism
o Hepatitis B and C
o Hemochromatosis
o Wilson disease

Question 20

manifestations of cirrhoses

Answer 20

o Asymptomatic
o Portal hypertension
o Liver failure

Question 21

clinical features of liver failure

Answer 21

• Multiple coagulation defects
• hypoalbuminemia
• jaundice
• hyperesterinism
• secondary hyperaldosteronism
• Hepatic encephalopathy
• You can get extra estrogens built up in the system

Question 22

liver failure

Answer 22

• Cholestasis
• Jaundice
• Multiple coagulation defects: Impaired synthesis of vitamin K dependent factors ; II, VII, IX, and X. PT is the best monitor of these defects and is not corrected with administration of vitamin K.
• Hypoalbuminemia: from decreased albumin synthesis reduces plasma oncotic pressure, hence predisposing to ascitis ad pitting edema.
• Inability to degrade hormones such as estrogen and 17-ketosteroids . This result in hyperestrenism in males characterized by the following signs; gynecomastia, spider angiomata, palmar erythema, testicular atrophy and female distribution of hair.
• Secondary hyperaldosteronism with retention of salt and water due to inability to degrade aldosterone.
• Hepatic encephalopathy: refers to a variety of neurological signs and symptoms in patients who suffer from chronic liver failure or in whom the portal circulation is diverted.

Question 23

Pancreas

Answer 23

• Large compound gland like salivary gland (Compound = more than one function, it makes more than one product)
• Duct cells secrete bicarbonate, acini secrete enzymes (Bicarb neutralizes stomach acids)

Question 24

pancreatic secretions

Answer 24

• Bicarbonate – buffers chyme exiting stomach (Chyme = last meal + all your gastric secretions, There is a fair amount of acid in the chyme once it leaves the intestine)
• Proteins (proteases) – trypsin and chymotrypsin (Pepsin breaks down peptides (proteins), Happens in the stomach)
• Starch – Amylase (Amylase is found in saliva, We break down carbohydrates first – they are our primary energy source and what we use to fuel our metabolism)
• Lipases – Pancreatic lipase, cholesterol esterase (Pancreatic enzymes need to finish off the digestion of carbs - Adds more amylase and finishes off chemical digestion of proteins, These enzymes also break down the fats (through the lipases), Multiple enzymatic products produced by pancreas (acini))
• Normally only become active on entering small intestine – why is this important? (SO THAT THEY DON’T DIGEST THE PANCREAS!! - When the pancreatic duct gets obstructed, this is exactly what happens!! We digest our own pancreas)
• Pancreas secretes 3L fluid/day
• When the pressure in the stomach is greater than the pressure in the pyloric sphincter, then the stomach content will get squeezed out (This makes sure that stuff is presented to the small intestine at a low rate)

Question 25

3 triggers

Answer 25

- Acetylcholine from parasympathetic fibers - Cholecystokinin (CCK) from duodenum – secreted by the gut and acts on the gut (Moves the gallbladder!! Contracts and squeezes out bile to help emulsify fat, TRIGGER FOR RELEASE IS FAT IN YOUR MEAL!! We’re gonna need more lipase and bile down here!) - Secretin from small intestine – causes large bicarbonate release (Signals the pancreas that you need more bicarb! - Most of the pancreatic secretion comes as the chyme is hitting the small intestine) - Most secretion stimulated during intestinal phase - This stimulation is coming from the brain (vagus nerve, CN 10) (Cortical control, central control of digestive process) - While this system has its own nervous system and can operate on its own, it is also highly susceptible to higher brain stimulus - Largest pool of serotonin in the body is in the gut, not in the brain

Question 26

secretin and CCK

Answer 26

- Secretin – 27 AA peptide (S cells), most potent trigger is acid in chyme - CCK – 33 AA peptide (I cells), stimulated by peptones and fatty acids in chyme - Comes with fats!! Eat a fatty meal, release more CCK - Both are endocrine hormones

Question 27

pancreatitis

Answer 27

- Mostly EtOH and biliary dz - Also drugs, trauma and viral causes - 90% damage required for exocrine dysfunction for maldigestion to manifest (Enormous safety factor – you can survive on 15-20% of your pancreas)

Question 28

workup

Answer 28

- PE difficult - History important – diet, alcohol, lipids, cholesterol, history of pancreatitis - Presentation – stabbing chest pain radiating to the back (Hot poker sticking straight into gut and through the back!! – BECAUSE IT’S A RETROPERITONEAL ORGAN! Like to lie very still or lean forward) - Labs: serum enzymes reliable at 3x normal values (That means its unreliable under this level, Normal levels of lipase is high tens, low hundreds (160ish) - You need it to be around 500 to be reliable)

Question 29

enzymes

Answer 29

- Leak out into blood when duct flow is obstructed - Serum Amylase –rises in 6-12 hr with short t1/2 - Amylase may not rise as high with alcoholic and high triglyceride conditions (Amylase is not specific, also made in the mouth, Lipase is much more specific – better test for pancreatitis than amylase) - Serum lipase rises in 4-8 hr, occurs earlier and lasts longer