CH 38 Disorders of the Hepatobiliary and exocrine pancreas function

Cholestasis

a decrease in bile flow through the intrahepatic canaliculi and a reduction in secretion of water, bilirubin, and bile acids by the hepatocytes. As a result, the materials normally transferred to the bile, including bilirubin, cholesterol, and bile acids, accumulate in the blood

Intrahepatic cholestasis

is a type of cholestasis that occurs within the liver due to conditions affecting bile production or transport, often leading to jaundice and pruritus. It can be caused by liver diseases, medications, or genetic disorders.

Extrahepatic Cholestasis

is a type of cholestasis caused by obstruction of the bile ducts outside the liver, leading to bile accumulation and jaundice. Common causes include gallstones, tumors, or strictures in the bile ducts.

Cirrhosis

A chronic liver disease characterized by the replacement of health liver tissue with scar tissues

Primary Biliary Cirrhosis/Primary sclerosing cholangitis

Both are autoimmune disorder that gradually destroys the bile ducts in the liver, leading to cholestasis and progressive liver damage.

Intrahepatic causes for Primary Biliary Cirrhosis/Primary sclerosing cholangitis

caused by disorders of the small intrahepatic canaliculi and bile ducts

Extrahepatic causes for Secondary Biliary Cirrhosis/Secondary sclerosing cholangitis

caused by conditions such as cholelithiasis, common duct strictures, or obstructing neoplasms, the effects begin with increased pressure in the large bile ducts.

Cholelithiasis

the formation of gallstones in the gallbladder, which can obstruct bile flow.

Neoplasm

Abnormal growth of tissues, tumor

Bylers syndrome

known as progressive familial intrahepatic cholestasis type I, which inadequate bile is produced resulting in inadequate fat breakdown and absorption due to mutations in ATP8B1 protein

Alagille syndrome

an autosomal dominant disease that involves the intrahepatic hypoplasia specifically of the bile ducts. (Under development of the bile ducts). People with this disease present with cardiac and eye abnormalities along with skeletal abnormalities in the facial bones

Hypoplasia

is a condition where there is incomplete development or underdevelopment of a tissue or organ.

Benign recurrent cholestasis

is a rare liver disorder characterized by episodes of cholestasis, leading to bile accumulation and potential liver damage, often due to an inherited defect.

What does prolong obstructive cholestasis lead to and why is it bad?

Prolonged obstructive cholestasis leads to bile acid accumulation, which can lead to fatty changes and possible rupture of the canaliculi leaking bile in hepatocytes, destruction of the supporting connective tissue, and reservoirs of bile containing cellular debris and pigment. Unrelieved obstruction leads to biliary tract fibrosis and end stage cirrhosis

Fibrosis

the process of excessive accumulation of scar tissue or fibrous connective tissue in organs or tissues as a response to injury, inflammation, or chronic disease.

Pruritus

Itch

Hyperlipidemia

high cholesterol

When testing for Impaired liver function what kind of tests should we doing?

Looking for increased levels of cholesterol in feces, bilirubin, and liver enzymes such as ALT and AST

What can cause other manifestation of reduced bile flow related to intestinal absorption?

nutritional deficiencies of fat-soluble vitamins such as A, D, and K

Bilirubin

bilirubin is the final product of the breakdown of heme contained in aged red blood cells, this is what gives bile its color. It is processed in the liver, conjugated to make it water-soluble, and then excreted into the bile for elimination via the intestines.

Explain bilirubin elimination

hemoglobin from the red blood cell is broken down to form biliverdin, which is converted to free bilirubin, which is transported in the blood and attached to albumin. free-Bilirubin is absorbed through hepatocytes, which is converted into conjugated bilirubin and now soluble in bile where it will then exit through digestive track.

Free Bilirubin

unconjugated bilirubin that circulates in the bloodstream attached to albumin, not water-soluble

Conjugated bilirubin

bilirubin that has been processed by the liver, making it water-soluble and ready for excretion into bile.

Normal levels of total serum bilirubin

less than 1.5 mg/dL (17 to 20.5 mol). Measurements include direct (conjugated) bilirubin, indirect (free) bilirubin, and total bilirubin

Jaundice

yellowish discoloration of skin and deep tissues from abnormally high levels of bilirubin. Occurs when there is a imbalance between the synthesis of bilirubin and clearance of bilirubin

Where should you look for jaundice?

Examine the skin, sclera, and mucous membranes for yellow discoloration. Look especially at the eyes due to bilirubin’s affinity for elastic fibers which the eyes have plenty of

What are the five major causes of jaundice

1. excessive destruction of red blood cells

2. impaired uptake of bilirubin by the liver cells

3. decreased conjugation of bilirubin

4. obstruction of bile flow in the canaliculi of the hepatic lobules or in the intrahepatic or extrahepatic bile ducts

5. excessive extrahepatic production of bilirubin

Prehepatic Jaundice

characterized by elevated levels of unconjugated bilirubin, or bilirubin not yet processed by the liver. Common cause: excessive red blood cell breakdown

intrahepatic jaundice

Liver cells themselves are damaged or impaired preventing them from properly processing and excreting bilirubin. Leads to mixtures of both conjugated and unconjugated bilirubin

Post-hepatic Jaundice (Cholestatic Jaundice)

Characterized by elevated levels of conjugated bilirubin meaning that bilirubin is being processed in the liver but cannot be excreted properly due to a blockage in the bile ducts

Neonatal hyperbilirubinemia

increased production of bilirubin in newborn infants and their limited ability to excrete it from 0-14 days old

Gilbert Disease

dominant genetic disorder which results in a reduced removal of bilirubin from the blood. This disorder is benign, and most people affected with it have no symptoms other than slightly elevated unconjugated bilirubin and mild jaundice

Hepatitis

Inflammation of the liver

Levels of serum Alkaline phosphate

reflect the activity of the enzyme of alkaline phosphatase in the blood. Normal ALP levels range from 44 to 147 UI/L

Enzyme Alkaline phosphatase

Enzyme that plays a role in various bodily functions including bone and liver health. Involved in processes like bone mineralization and nutrient transport

Aminotransferase levels

specifically, ALT (alanine aminotransferase) and AST (aspartate aminotransferase) primarily found in liver and muscles. elevated levels in the blood can indicate liver damage. Normal range for ALT is 7 to 56 UI/L and for AST is 8 to 33 UI/L.

Two enzymes that are the most important for checking liver functions

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which help assess liver health and function.

Carcinoma

Type of cancer that develop in epithelial cells, cells that lines the body’s internal organs and outer surfaces

Hypoxic

insufficient oxygen to tissues

Reye syndrome

Rare but serious condition that primarily affecting children and teenagers, causes swelling in the liver and brain. Exact causes are unknown, but complications can include coma, seizures, or death.

Hypoalbuminemia

low albumin levels in the blood

How do we check synthestic capacity in the liver?

measure serum protein levels and prothrombin time as indicators of liver function.

Serum Protein Levels

typically measured to assess overall protein status and can help identify potential health issues
Normal Serum Protein levels:
- total protein: 6.4 to 8.3 g/dL
- Albumin: 3.5 to 5.0 g/dL
- Globulin: 2.3 to 3.4 g/dL

Prothrombin time

a blood test that measures how long it takes for blood to clot, often used to assess liver function and vitamin K levels. average time for blood to clot is about 10-13 seconds

GGT test

a blood test used to check for liver damage or disease. Measures the amount of GGT, a liver enzyme. High levels can indicate various health condition affecting the liver, heart or other organs Normal levels include:

males: 0-65 IU/L

females: 0-50IU/L

children: 0-30 IU/L

Ultrasonography

also known as ultrasound or sonography is a non-invasive medical imaging technique that uses sound waves to create pictures of internal organs and tissues

Portal Hypertension

a condition characterized by abnormally high blood pressure in the hepatic portal vein. this happens blood flow is obstructed

Three major types of reactions are involved in the hepatic detoxification and metabolism of drugs and other chemicals and what is involved in them

1. Phase 1 reactions - involve chemical modification or inactivation of substance

2. Phase 2 reactions - involve conversion of lipid-soluble substance to water-soluble derivatives

3. Phase 3 reactions - involved the substance, its metabolites, or conjugates being secreted as bile

Autoimmune Hepatitis (AIH)

a chronic liver disease where the body’s immune system attacks liver cells causing inflammation and potential damage to the liver.

Hepatitis A

transmitted through contaminated food or water or through close interaction with an infected person

Hepatitis B

Transmitted through contact with infected blood or body fluids

Hepatitis C

a viral infection that is primarily spread through blood-to-blood contact, often leading to chronic liver disease.

fatty liver disease

a condition characterized by an accumulation of fat in liver cells, often associated with obesity, alcohol consumption, and metabolic disorders. It can lead to inflammation, liver damage, and eventually cirrhosis if not managed properly.

Non-alcoholic fatty liver disease

causes include obesity diabetes or high cholesterol, or other metabolic dysfunctions that affect the liver. It is characterized by fat accumulation in the liver without significant alcohol consumption, potentially leading to inflammation and liver damage.

Alcoholic fatty liver disease

Occurs due to heavy alcohol consumption leading to fat buildup in liver cells, which can cause inflammation and liver damage, potentially progressing to alcoholic hepatitis or cirrhosis. Problem can be remedied by discontinuing the heavy use of alcohol and implementing lifestyle changes such as diet and exercise to support liver health.

nonalcoholic steatohepatitis

a more severe form of non-alcoholic fatty liver disease (NAFLD), characterized by inflammation, liver cell injury, and fibrosis. It can progress to cirrhosis and increases the risk of liver cancer.

What affect does alcohol have on the liver?

Acetaldehyde which is the byproduct of alcohol metabolism in the body which when binds with cells that are not hepatocytes, they can lead to a toxic effect, causing inflammation and cell damage. In order to get rid of this acetaldehyde the liver needs to process it, but excessive consumption overwhelms its capacity, resulting in liver damage.

Alcoholic hepatitis

intermediate stage between fatty changes and cirrhosis. It is often seen after an abrupt increase in alcohol intake and is common in binge drinkers.

Post hepatic obstruction

refers to any obstruction to blood flow through the hepatic veins beyond the liver lobules, either within or distal to the liver.

Thrombosis

The formation of a blood clot inside a blood vessel obstructing the flow of blood through the circulatory system

Veno-occlusive disease

also known as sinusoidal obstructive syndrome that occurs when small veins in the liver become blocked, leading to liver damage and potentially liver failure.

Budd-Chiari Syndrome

rare liver disorder characterized by obstruction of the hepatic venous outflow (veins that drain blood from liver are blocked) which leads to blood and fluid build up in the liver and abdomen

polycythemia vera

A blood disorder characterized by the overproduction of red blood cells, often increasing blood viscosity and leading to complications such as thrombosis.

hypercoagulability/thrombophilia

blood is more likely to cloth than normal due to various factors, which can increase the risk of thrombosis and related complications.

Sinusoidal obstruction syndrome

also known as veno-occlusive disease that occurs when small veins in the liver become blocked, leading to liver damage and potentially liver failure.

Portosystemic shunts

abnormal connections between the portal and systemic venous circulation, often leading to complications like hepatic encephalopathy or portal hypertension.

splenomegaly

enlargement of the spleen due to many reasons but can be also due to portal hypertension and the shunting of blood into the splenic vein.

hepatic encephalopathy

refers to the totality of central nervous system manifestation of liver failure. Characterized by neural disturbances ranging from a lack of mental alertness to confusion, coma, and convulsions.

Ascites

when the amount of fluids in the in the peritoneal cavity is increased and is a late-stage manifestation or cirrhosis and portal hypertension.

Hypersplenism

characterized by a decrease in the lifespan of all the formed elements in the blood and a subsequent decrease in their numbers, leading to anemia, thrombocytopenia and leukopenia

Caput medusae

refers to the appearance of enlarged dilated veins radiating from the umbilicus across the abdomen.

vascular spiders

are small, spider-like blood vessels that appear on the skin, often associated with liver disease, particularly cirrhosis.

telangiectasis

small, dilated blood vessels that are visible near the surface of the skin or mucous membranes

spider angiomas

are benign vascular lesions characterized by a central red spot with radiating capillaries, commonly seen in liver disease.

spider nevi

are similar to spider angiomas, featuring a central red spot with thin, dilated blood vessels extending outward, often indicative of liver dysfunction.

Azotemia

elevated levels of nitrogenous waste products primarily urea and creatinine in the blood

Oliguria

decreased urine output

hepatorenal syndrome

a serious condition characterized by kidney failure secondary to liver disease, often associated with advanced cirrhosis and portal hypertension. Characterized by reduced blood flow to the kidneys

Hepatocellular Carcinoma

Most common type of primary liver cancer, often associated with liver diseases like cirrhosis or hepatitis

cholangiocarcinoma

bile duct cancer, rare but aggressive type of cancer that arises from the cells lining the bile ducts, often presenting with jaundice, weight loss, and abdominal pain.

Metastatic Tumor

a tumor that has formed in another part of the body after cancer cells have spread from the original tumor to nearby or distant sites, often affecting the liver as a common site for metastasis.

Cholelithiasis

gallstone disease characterized by the formation of solid stones in the gallbladder, which can lead to biliary colic, cholecystitis, and other complications. Two kinds of gall stones, cholesterol stones and pigment stones

Acute vs Chronic Cholecystitis

Acute, sudden onset. Chronic reoccurring.

Acute is often caused by such things like gallstones, while chronic is long-standing inflammation of the gallbladder often resulting from repeated attacks of acute cholecystitis

Choledocholithiasis

Bile duct stones, refers to gallstones in the common bile duct. The stones start in the gallstone and move down to the bile duct and cause obstructions to the flow of bile.

Cholangitis

inflammation of the bile ducts, often due to infections from blackages or gallstones, leading to pain, fever, and jaundice.

Gallbladder Cancer

rare type of cancer originating in the gallbladder, often diagnosis in later stages due to lack of symptoms

Acute pancreatitis

sudden inflammation of the pancreas, often caused by gallstones or heavy alcohol use, leading to abdominal pain, nausea, and vomiting.

Chronic Pancreatitis

progressive inflammatory disease of the pancreas that affects both functions of the pancreas and can lead to chronic pain, malabsorption, and diabetes.

Pancreatic Cancer

develops in pancrease, often diagnosed late and associated with poor prognosis. often fatal

Pigment stones

less common, these stones are made of bilirubin a waste product of red blood cells, this could be an identification of other underlining blood/liver diseases

Cholesterol Stones

Most common type and are primarily composed of cholesterol