Hepatic & Biliary Disease (Liver + Gallbladder)

Question 1

Describe the dual blood supply in the liver/gallbladder?

Answer 1

Question 2

Describe the portal system

Answer 2

• Normally blood flows Heart → Artery → Capillary → Vein → Heart in a portal system, a second set of capillaries is added:
• Heart → Artery → Capillary → Vein → Capillary → Vein → Heart
• Invariably, something is picked up by the first set of capillaries & dropped off at the second set

Question 3

Describe the Hepatic Portal System

Answer 3

Question 4

What is Caput Medussae?

Answer 4

• is the appearance of distended and engorged superficial epigastric veins, which are seen radiating from the umbilicus across the abdomen

Question 5

What is CCK?

Answer 5

• Cholecystokinin (CCK - formerly known as pancreozymin)
• peptide hormone produced by enteroendocrine cells in the first part of the duodenum that aids in digestion of fats & proteins.
• When reaching the 2nd part of the duodenum, it stimulates contraction of the gallbladder and release of bile ( & release of enzymes from exocrine pancreas)
• CCK is also sensory neuron transmitter. Release of CCK from 5th nerve sensory neurons in the iris leads to miosis in uveitis and iris injury

Question 6

Describe gallstones & biliary obstruction?

Answer 6

• Stones are either cholesterol or “pigmented” meaning they contain bile salts
• Often asymptomatic
• Symptoms = pain after a fatty meal that radiates to tip of right shoulder (phrenic)
• More severe complications include
  
  • inflammation of gallbladder (choelecystitis)
  • biliary tree (cholangitis)
  • obstructive cholestasis
  • Pancreatitis
• Gall bladder can be resected but digestion of fat is compromised

Question 7

What are the major primary diseases of the liver?

Answer 7

• The major primary diseases of the liver are…
  
  • Viral hepatitis
  • Nonalcoholic fatty liver disease (NAFLD)
  • Alcoholic liver disease
  • Hepatocellular carcinoma (HCC)
  • Metastatic liver disease

Question 8

What are some ways we can diganose liver disease?

Answer 8

• One of the main ways that diagnosis of liver disease is made is baesd upon results of the liver function tests, which assess four main aspects of the liver structure & function
• Liver function tests can be used to
  
  • Screen for liver infections, such as hepatitis
  • Monitor the progression of a disease, such as viral or alcoholic hepatitis, and determine how well a tx is working
  • Measure the severity of a disease, particularly scarring of the liver (cirrhosis)
  • Monitor possible side effects of medications

Question 9

Describe what you should see during LFTs (Liver function tests) when liver is damaged?

Answer 9

• If liver cells are injured these enzymes are released into the blood
• If liver is damaged, breakdown and excretion of hemoglobin is reduced (by-products build up in tissues)
• Bile production is compromised
• With liver damage these do not get made, leading to predictable consequences
  
  • Edema from disruption of starlings equilibrium inability to clot
  • Jaundice (icterus)
  • Portal hypertension
  • Altered drug metabolism

Question 10

Describe RBC Breakdown

Answer 10

• Old RBCs are killed by macrophages in the spleen
• Hemoglobin is broken into heme & globin.
  
  • The globin is broken into constituent aa and reused
  • The heme constituent of hemoglobin is broken down into iron (Fe3+) and protoporphyrin and then biliverdin.
    
    • The biliverdin is reduced to unconjugated bilirubin, which is released into the plasma and recirculated to the liver bound to albumin because it is not water soluble

Question 11

In 6 min & 40 sec = 400 sec, your body kills off ______ RBCS & each RB contains ____ hemoglobin

Answer 11

• 800 million RBCs
• 250 million molecules of hemglobin = 21.25 x 10¹² molecules of hemoglobin

Question 12

What does this image show?

Answer 12

• Scleral Icterus (Jaundice)

Question 13

How would you treat post-partum jaundice?

Answer 13

• Years ago the whole isolette was blasted with UV light, which is harmful to the retina. As such, the babies had to have their eyes fully covered
• Then came bilibelts & biliblankets, wrapped against the skin of teh abdomen & back. The blue light you see escaping is not UV & does not need to cover eyes.

Question 14

Describe Drug or toxin induced liver injury

Answer 14

• Most drugs or toxins affecting the liver may be classified
  
  • Predictable hepatotoxins, acting in a dose-dependent manner & occurring in most individuals
  • Unpredictable or idiosyncratic hepatotoxins, which happen in rare individuals and which are often independent of dose
• Hepatotoxins may cause harm from direct cell toxicity through hepatic conversions of a xenobiotic to an active toxin, or by immune mechanisms, such as by the drug or a metabolite acting as a hapten to convert a cellular protein into an immunogen
• The most common hepatotoxin causing acute liver failure is acetominophen and ASA, greater than 2 gms/day
  
  • ​both of these are dose-dependent
  • One aspirin tablet is 325mg; one acetominophene is 500mg
• The most common hepatotoxin causing chronic liver disease is alcohol

Question 15

What are the most common medicatiosn that require monitoring LFTs?

Answer 15

• Statins - very common
• Amiodarone (anti-arrhythmic) - also produces veroticeal keratopathy
• Anti-arthritic use of oral gold (rare these days)
• Methotrexate (DMARD) - Anti-IL-1 and other anti-inflammatory actions; for RA. Inhibit folate biochemistry and therefore production of DNA, RNA in cancer
• Anti TB drugs
• Anti-fungals
• Acetominophen for chronic use in systemic inflammatory disease

Question 16

Describe the first pass pharmacokinetics?

Answer 16

• A phenomenon of drug metabolism whereby the concentration of drug is greatly reduced before it reaches the systemic circulation
• After a drug is swallowed, (Enteral or PO- per os ADMINISTRATION) it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the LIVER before it reaches the rest of the body.
• The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from liver to reach therapeutic concentrations at the target tissue (Bioavailability)
• The four primary systems that affect the first pass effect of a drug are the enzymes of the GI lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes
• In drug design, drug candidates may have good druglikeness but fail on first-pass metabolism because it is biochemically selective
• Alternative routes of administration (PARENTERAL) . like suppository, intravenous, intramuscular, inhalation aerosol, transdermal, and sublingual avoid the first pass effect because they allow drugs to be absorbed directly into the systemic circulation
• Drugs with high first pass effect have a considerably higher oral dose than sublingual or parenteral dose. There is marked individuals variation in the oral dose due to differences in the extent of first pass metabolism
• Importantly oral bioavailability is increased in pt with severe liver diseases like cirrhosis requiring altering of dose

Question 17

Describe copper dependent enzymes

Answer 17

• Copper is absorbed in the stomach, transported with a chaperone protein ceruloplasmin, stored in the liver and ecreted into the bile.
• Dietary soruces include seafood, whole grains (beans & lentils) and chocolate, pluts nuts, lemons and raisins.
• Other food sources of copper include cereals, potatoes, peas, red meat, mushrooms and dark leafy vegetables

Question 18

Describe Wilson (hepatolenticular) disease

Answer 18

• it is an AR disorder caused by putation of ATP7B gene, resulting in impaired copper excretion into bile and a failure to incorporate copper into ceruloplasmin
• These changes cause copper accumulation in the liver & other tissues (brain & eyes) and a decrease in circulating ceruloplasmin.
• The accumulated copper cause toxic liver injury by three mechanism
  
  • Promoting formation of free radicals by the fenton reaction
  • binding to sulfhydryl groups of cellular proteins
  • Displacing other metals from hepatic metalloenzymes
  • They usually do NOT have elevated copper levels in blood since the only way for copper to get into blood is bound to ceruloplasmin & ceruloplasmin levels are abnormally low

Question 19

What are the sx for wilson (hepatolenticular) disease? and what are some tx?

Answer 19

• Sx typically begin between teh ages of 12 and 23
  
  • Fatigue, lack of apetite, abdominal pain
  • Jaundice (yellowing of skin & eyes)
  • Bruise easily
  • Fluid build up in legs/abdomen
  • Problems with speech, swallowing, physical coordination
  • Uncontrolled mvmt/muscle stiffness
  • Cataracts & corneal findings
• Catching Wilsons’ early is critical. Treated early with chelating agents, many pt can live a fairly normal life
  
  • Penicillamine (cuprimine, Depen) = can cause serious side effects, including skin problems, bone marrow suppression and worsening of neurological sx.
  • Trientine (syprine) = works like penicillamine but tends to cause fewer side effects