HEPATOBILIARY FUNCTION GI SYSTEM alterations

HEPATOBILIARY FUNCTION (hepato= live biliary=bile)

Metabolic Functions of the Liver

• liver anatomy and blood supply

• Carbohydrate Metabolism & Glucose Homeostasis

• Protein Synthesis & Conversion of Ammonia to Urea

• Pathways of Lipid Metabolism

• Bile Production & Cholestasis

• Bilirubin Elimination

• Coagulation

Liver Anatomy & Blood Supply

• Largest visceral organ; protected by rib cage and not palpable in healthy people

  • Someone who has cirrhosis you can palpate liver (feel it)

• Divided into two large lobes and two smaller lobes

• Receives ~ 25% of resting cardiac output!

  • can be affected by low CO

• unique , dual blood supply

  •   Hepatic artery: 25% of blood enters through this artery

  •   Portal vein: Remaining 75% enters liver through the valveless portal vein. This vein comes from the digestive tract and major abdominal organs and carries nutrients and toxins absorbed from the intestines.

    it Feeds off intestines esophagus rectum

    
    

25% of blood enters through this artery

hepatic artery

What is being described

•   Remaining 75% enters liver through the valveless portal vein. This vein comes from the digestive tract and major abdominal organs and carries nutrients and toxins absorbed from the intestines.

  • Feeds off intestines esophagus rectum

portal vein

Metabolic Functions of the Liver:

Carbohydrate Metabolism & Glucose Homeostasis

• Stores large amounts of glucose as glycogen.

• When blood glucose levels are low, glycogenolysis occurs (conversion of glycogen back to glucose)

• Gluconeogenesis: Synthesizes glucose

• Converts excess carbs to triglycerides stored in adipose tissue

• If liver failing, blood sugar will be low

Metabolic Functions of the Liver:

Protein Synthesis & Conversion of Ammonia to Urea

• Synthesizes albumin(protein)-

  • contributes to colloidal osmotic pressure and the binding & transport of many substances

    •   Low albumin with liver failure, albumin holds fluid, without it it leaks out, leading to swelling

• Converts ammonia (the by-product of amino acid metabolism) to urea (excreted by the kidneys)

  • Too much ammonia = toxin, so if liver is failing and cant convert it builds up which can affect the brain

Metabolic Functions of the Liver:

Pathways of Lipid Metabolism

• Certain aspects of lipid metabolism occur mainly in the liver

• Oxidation of free fatty acids to keto acids supply energy for body functions

Metabolic Functions of the Liver:

Bile Production & Cholestasis

• Liver produces 500-600 mL green/yellow bile daily

• Bile contains water, bile salts, bilirubin, cholesterol, and by-products of metabolism

• Bile is essential for the digestion of fats and the absorption of fats and fat-soluble vitamins(k) from the intestines

• Cholestasis is a decrease in bile flow

Metabolic Functions of the Liver:

Bilirubin Elimination

• Bilirubin-

  • final product of the breakdown of the heme unit in red blood cells

• Gives bile it’s color

• Unconjugated (“free”, bad) bilirubin is insoluble in plasma. It’s converted to conjugated (soluble) bilirubin in the liver.

  •    We can get rid of soluble bilirubin

• Excreted in the feces; absorbed in portal circulation

• Normal total bilirubin levels in the blood: 0.1 – 1.5 mg/dL

• Elevated bilirubin —» Jaundice

  • Yellow discoloration of skin and other tissues as the result of abnormally high levels of bilirubin in the blood

  • Five major causes:

    • excess destruction of RBCs,

    • impaired bilirubin uptake by liver cells,

    • decreased bilirubin conjugation,

    • obstruction of bile flow,

    • excessive production of bilirubin

What is the final product of the breakdown of the heme unit in red blood cells

bilrubin

What is the (“free”, bad) bilirubin is insoluble in plasma.

unconjugated bilirubin

What is the (soluble) bilirubin

conjugated bilirubin

What is the normal total bilirubin levels in the blood:

0.1 – 1.5 mg/dL

Elevated bilirubin —> Jaundice

• Yellow discoloration of skin and other tissues as the result of abnormally high levels of bilirubin in the blood

• Five major causes:

  • excess destruction of RBCs

  • , impaired bilirubin uptake by liver cells,

  • decreased bilirubin conjugation,

  • obstruction of bile flow,

  • excessive production of bilirubin

Coagulation

The liver synthesizes almost all clotting factors.

• People with liver disease prone to bleeding

What are the tests of Hepatobiliary Function – “Liver Function Tests” “LFTs”

All of the following are usually elevated with liver disease EXCEPT albumin

• Used to aid in the diagnosis of liver disease

  • Alanine aminotransferase (ALT) liver specific

  
  

  • Aspartate aminotransferase (AST)

  
  

  • Ammonia (NH3)

    • starts to rise in late stage

  
  

  • Bilirubin

  
  

  • Coagulation factors such as prothrombin time (PT)

    •   Seeing how long it takes the blood to clot (coagulate)

      With liver disease it takes a longer time to clot

• albumin: decreased with liver disease

• radiology: ultrasound, computed tomography (CT), biopsy

Hepatotoxic Disorders: Drug-Induced Liver Disease

1.    Liver is responsible for metabolizing most drugs and converting lipid-soluble substances to water soluble substances

2. Many drugs, herbal substances, and other substances are “toxic” to the liver (example: acetaminophen is hepatotoxic)

3. Factors contributing to susceptibility of drug-induced liver disease

   • genetics

     • some people may have a weaker liver

   • age differences

   • underlying chronic liver disease

   • alchohol consupmption and diet

   • use of multiple interacting drugs

What is viral hepatitis

Hepatitis: Inflammation of the liver

Causes of hepatitis :

o   Viruses

o   Autoimmune disease

o   Reactions to drugs/toxins

o   Secondary to other disorders

Risk factors of viral hepatitis

o   IV drug use

o   Sexual promiscuity

• Multiple sexual partners

o   Healthcare workers

• At higher risk for Hep B, due to blood exposure

o   Exposure to blood/body fluids

Manefestations of viral hepatitis is divided into three phases:

o   Prodromal (pre-icterus) period (Icterus means jaundice)

o   Icterus period- Follows prodromal period by 7-14 days

o   Recovery period- Complete recovery by 1-4 months

Manefestation phase one of viral hepatitis

Prodromal (pre-icterus) period (Icterus means jaundice)

• general malaise

• myalgia

  • muscle pain

• athralgia

  • joint pain

• easily fatigues

• anorexia

• possible GI symptopms

• rise in bilirubin —> jaundice —→ icterus period

Manefestation phase one of viral hepatitis

o   Icterus period- Follows prodromal period by 7-14 days

•   Tenderness around liver area

• Mild weight loss

• Spider angiomas

  •    Collection of blood vessels, looks like a little firework

Manefestation of the third phase viral hepatitis

o   Recovery period- Complete recovery by 1-4 months

• Feels better

• Appetite returns

• Jaundice disappears

Hepatitis chart

Type	Etiology & Pathogenesis	Incubation(don’t need to know)	Clinical Course	Other Info
Hepatitis A	Fecal-oral route	14-28 days	Usually self-limiting(runs its course)	Vaccine available
Hepatitis B	Blood   Secretions (ex: semen)   Blood transfusions (rare)   Maternal-fetal   Spreds through “blood booty and babies)	Longer than Hep A	More serious health problem than Hep A   May be a chronic carrier	·      Many people may have chronic, asymptomatic Hep B infections ·      Testing for the HBV recommended for high risk populations ·      Vaccine available
Hepatitis C	Blood transfusions (rare) IV drug use Sexual contact	2-26 weeks	May be unaware they have it	·      Most develop chronic hepatitis ·      Serious consequences include cirrhosis & end-stage liver disease, cancer.
Hepatitis D	Similar to Hep B			·      Requires assistance of Hep B to replicate ·      Hep B vaccine helps aid in prevention
Hepatitis E	Fecal-oral route		Manifestations similar to A	·      Rare in US ·      High mortality rate for pregnant women ·      Immunocompromised at risk for developing chronic state

Type	Etiology & Pathogenesis	Incubation(don’t need to know)	Clinical Course	Other Info
	Fecal-oral route	14-28 days	Usually self-limiting(runs its course)	Vaccine available

What hepaititis is this

Hepatitis A

What hep is this

Type

etilology and pathogenis Blood   Secretions (ex: semen)   Blood transfusions (rare)   Maternal-fetal   Spreds through “blood booty and babies)

incubation Longer than Hep A

clinical More serious health problem than Hep A   May be a chronic carrier

other info: ·  Many people may have chronic, asymptomatic Hep B infections ·Testing for the HBV recommended for high risk populations · Vaccine available

Hepatitis B

What hepatitis is this

Etiology & Pathogenesis Blood transfusions (rare) IV drug use Sexual contact

Incubation(don’t need to know) 2-26 weeks

clinical course: May be unaware they have it

other info ·      Most develop chronic hepatitis ·      Serious consequences include cirrhosis & end-stage liver disease, cancer.

Hepatitis C

What hepatitis is being described

etiology and pathogenesis Similar to Hep B

incubation(dont need to know)

clinical course: nothing

other info: · Requires assistance of Hep B to replicate ·      Hep B vaccine helps aid in prevention

Hepatitis D

What hepatitis is being described

etiology and pathogenesis: Fecal-oral route

incubation(dont need to know)

clinical course: Manifestations similar to A

other info: · Rare in US ·  High mortality rate for pregnant women · Immunocompromised at risk for developing chronic state

Hepatitis E

What is chronic viral hepatitis

1.     Chronic inflammation of the liver; > 3-6 months

2.     Primary cause of chronic liver disease, cirrhosis, and liver cancer; chief reason for liver transplantation in adults

3.     Caused by HBV, HCV, or HDV

4.     Most common manifestations: fatigue, malaise, loss of appetite, and occasional jaundice

What is Alcohol-Induced Liver Disease

1.     80%-90% of alcohol is metabolized by the liver.

2.     The metabolism of alcohol—> damages certain membranes of the liver and—> may lead to chronic liver disease

•    Fatty liver – accumulation of fat in the hepatocytes, called steatosis

•   Alcoholic hepatitis

•    Alcoholic cirrhosis

3.     Amount of alcohol required to produce chronic liver disease varies. Affected by body size, age, sex, and ethnicity. High end is about 80 g/day for 10-12 years.

Examples:

a.     8 oz of 86 proof whisky

b.     Two bottles of wine

c.     Six 12 oz bottles of beer

What is the  accumulation of fat in the hepatocytes, called steatosis

fattly liver

What is

1.     End-stage chronic liver disease

2.     Much of the functional liver tissue has been replaced with fibrous scar tissue

cirrhosis

Manefestations of Cirrhosis

a.     Weight loss (may be masked by ascites)

b.     Weakness

c.     Anorexia

d.     Change in bowel habits

e.     Hepatomegaly

f.      Jaundice

g.     Abdominal pain

Late manfestations of cirrhosis (related to portal hypertension and liver failure):

•   Splenomegaly

  •    Enlarged spleen

• ascites

•   Portosystemic shunts

  • (esophageal varices, hemorrhoids)

• bleeding

  • (because we dont have our clotting factor)

• thrombocytopenia

  • (decrease in platelets)

• gynecomastia

  • (development of breast tissue in men)

• testicular atrophy

• spider angiomas

• palmar erythmea

  • (redness in palms of hands)

• hepatic encephlopathy

  • (brain disease because of liver), it starts to happen when ammonia builds up, and we start to see changes

• asterixis

  • (patients hands will flap and shake)

What is liver cancer

1.     Primary liver cancer is rare. Usually liver cancer is secondary cancer (liver metastasis)

2.     Hepatocellular carcinoma is the most common primary liver tumor

a.     Etiologic agents: viral hepatitis, long term exposure to environmental agents, drinking water contaminated with arsenic.

b.     Manifestations: Weakness, anorexia, weight loss, fatigue, abdominal swelling, sensation of abdominal fullness, dull/aching abdominal pain.

3.     Cholangiocarcinoma: Cancer of the bile ducts; rare

What is heptocellular carcinoma (type of liver cancer)

• the most common primary liver tumor

• Etiologic agents:

  • viral hepatitis,

  • long term exposure to environmental agents

  • , drinking water contaminated with arsenic.

Manefestations of Hepatocellular carcinoma (type of liver cancer)

• Weakness

• , anorexia,

• weight loss,

• fatigue,

• abdominal swelling,

• sensation of abdominal fullness,

• dull/aching abdominal pain.

What is Cholangiocarcinoma (type of liver cancer)

Cancer of the bile ducts; rare

What is being decribed

1.     “Gallstones”

2.     Caused by precipitation of substances in the bile, mostly cholesterol (80%) and bilirubin

3.     Two primary factors contributing to the formation of gallstones:

• a.     Abnormalities in the composition of bile (i.e., increased cholesterol)

• b.     Stasis of bile

4.     Risk factors: Female (especially women with multiple pregnancies or taking oral contraceptives), obesity

Cholelithiasis  (chole= gallbladder) (lithiasis= stone)

Manefestations of Cholelithiasis  (chole= gallbladder) (lithiasis= stone)

• indigestion

• Bililiary colic

  • pain in RUQ or epigastric and radiated to upper back/right shoulder

• jaundice if obstruction is present

What is

1.     Inflammation of the gallbladder

2.     Usually secondary to obstruction of the gallbladder outlet (associated with cholelithiasis)

Cholecystitis

manefestations of Cholecystitis

a.     Acute onset RUQ or epigastric pain

b.     Anorexia, nausea, vomiting

c.     Fever

What disorder of exocrine pancreas is being described

1. Reversible inflammation of the pancreas

2. Caused by premature activation of pancreatic enzymes

3. Pancreatic enzymes invade the pancreas and surrounding tissue

4. “Autodigestion” occurs —> Acute inflammatory response causes tissue damage and may lead to a systemic inflammatory response

Risk factors:

• alcoholism

• hyperlipidemia

• obstructive biliary disease (cholelithiasis)

• trauma

Acute Pancreatitis 

Manefestations of Acute Pancreatitis

• Abdominal pain* - epigastric or periumbilical area, radiating to back, chest, or flank

• Pain is worse when lying flat

  • it feels better to be in the fetal positon

 

•   Fever

• Tachycardia

  •   Painful and gets heart rate going

  •   Fluid shifts, which can make us hypovolemic= tachycardia

• Hypotension

• Respiratory distress

•   Abdominal distension

•   Jaundice

Labs of Acute Pancreatitis

Elevated amylase/lipase

             i.     Pancreatic enzymes

Elevated bilirubin

Elevated WBC

Elevated glucose (why?)

            i.      Because it damages beta cells

What is

Irreversible, progressive destruction of the pancreas by fibrosis. (Destruction of the endocrine pancreas occurs later)

Chronic Pancreatitis

Causes of Chronic Pancreatitis

a.     Long term alcohol abuse

b.     Long-standing obstruction of the pancreatic duct

c.     Cystic fibrosis

d.     Genetic disorders

e.     Neoplasms

Manefestations of Chronic Pancreatitis

similar to acute, but with less severity

common:

•   Anorexia

• , nausea,

• vomiting,

• constipation

• flatulence

Longterm complications of Chronic Pancreatitis

• Diabetes mellitus

  • Cells that secrete insulin can become completely destroyed leading to this

• Malabsorption syndrome

What is being described

1.     Most common type: pancreatic adenocarcinoma

2.     Typically no symptoms at first and spreads quickly

3.     High mortality rate

4. Cause unknown. Risk factors: smoking, alcohol, obesity, diabetes mellitus, male gender,

5. Deep vein thrombosis- fairly common with pancreatic cancer.

pancreatic cancer

Manefestations of pancreatic cacner

•    Pain, jaundice, weight loss

•   Most common symptom- dull epigastric pain with back pain, worse lying on back, better sitting forward