Week 3 - Liver, Gall Bladder, Pancreas and Associated Disorders Flashcards
Outline the hormonal and nervous controls that regulate the secretion of bile and pancreatic juice.
Hormonal regulation
1. CCK (cholecystokinin) and secretin released by duodenal enteroendocrine cells, in response to fatty, acidic or protein-rich chime
- CCK involved in pancreatic secretion (enzyme component), gall bladder contraction and relaxation of the hepatopancreatic sphincter
- Secretin is involved in pancreatic secretion (H2O and HCO3- component) and bile secretion
Also note: return of bile salts from enterohepatic circulation leads to bile secretion
Nervous regulation:
1. Vagal stimulation leads to pancreatic secretion and gall bladder contraction
List the components of pancreatic juice.
Key contents: enzymes, water and electrolytes (HCO3)
Pancreatic enzymes (PLAN)
- proteases
- lipases
- amylase
- nucleases
List the nutrients absorbed by each GIT region.
Stomach: water, alcohol
Duodenum: iron, calcium, fats, sugars, water, proteins, vitamins, magnesium, sodium
Jejunum: sugars, proteins
Ileum: bile salts, vitamins B12, chloride
Colon: water, electrolytes
Differentiate the terms cirrhosis and hepatocellular failure
Cirrhosis refers to structure change of the hepatocyte, whilst hepatocellular failure refers to the impaired hepatocyte function
List the sphincters of the biliary tree
Sphincter of the pancreatic duct - around the terminal part of the pancreatic duct
Sphincter of the bile duct - around terminal part of the bile duct
Hepatopancreatic sphincter (sphincter of Oddi) - found around the hepatopancreatic ampulla
Is this organ covered by peritoneum?
Gall bladder surface attached to liver has an adventitia Peritoneal surface (not attached to an organ) is covered by serosa
Attachments or location of round ligament
Contained within the free edge of the falciform ligament
Attachments or location of smaller omentum
Connects to the lesser curvature of the stomach and proximal part of the duodenum to the liver
Liver attachments: fissures of the ligamentum venosum and porta hepatis (undersurface)
Describe some potential clinical features of liver cancer
- irregular hepatomegaly, RUQ pain, jaundice
- symptoms of cirrhosis e.g. ascites
- constitutional symptoms (e.g. anorexia, weight loss, fever)
Explain how pancreatic proteases interact with the enzymes of the intestinal brush border.
Enteropeptidase (brush border enzyme) also converts pancreatic proteases to their active form
(trypsinogen to trypsin; chymotrypsinogen to chymotrypsin)
Define the term cystic fibrosis
A disorder of exocrine glands, in which the secretions of the lungs, pancreas, bile ducts and reproductive tract have increased viscosity
List the potential modes of transmission for the hepatitis viruses (HAV, HBV, HCV). Which of these viruses are vaccine-preventable?
HAV
- transmission by faecal/oral route
- yes to vaccination
HBV
- transmission by parenteral (via blood), sexual contact and perinatal
- yes to vaccination
HCV
- transmission by parenteral, perinatal (via placenta), possibly sexual
- vaccination not available
What is the neurovascular supply of the gall bladder?
Arterial supply: cystic artery (off right hepatic artery)
Venous drainage: cystic vein drains directly into liver or into portal vein
Nerve supply:
- parasympathetic: CNX vagus
- sympathetic: splanchnic nerve (T5-T9) via celiac plexus
- sensory: right phrenic nerve (important for pathology of GB visceral referred pain to right shoulder)
Describe the potential complications of cirrhosis. Are you able to identify the pathological basis for each complication?
Portal hypertension
- structural change to hepatocyte obstructs nutrient flow (leads to ascites due to accumulation of fluid in peritoneal cavity; splenomegaly due to passive congestion; varicose veins)
Hepatocellular failure
- hepatic encephalopathy
- coagulation defects
- endocrine changes
- peripheral oedema
What are the parts of the gall bladder?
Fundus: wide end, projects from the inferior border of the liver
Body: contacts the visceral surface of the liver
Neck: narrow tapered region, makes an S-shaped bend and is continuous with the cystic duct
Describe the potential complications of gallstones. How might these complications present?
Acute cholecystitis (impaction of cystic duct results in biliary stasis, thus acute inflammation) Chronic cholescystitis (GB wall becomes fibrotic and shrunken followed by repeated bouts of acute inflammation) Mucocele development (GB becomes distended with mucoid watery fluid) Infection (increased risk of bacterial infection, persistent inflammation and infection can result in empyema) Increased risk for carcinoma (mechanism unknown) Choledocholithiasis (impaction of gallstone in the bile duct results in inflammation of bile duct) Acute pancreatitis (obstruction at hepatopancreatic ampulla generates back-pressure, causes secretions to flow back up the pancreatic duct)
Provide examples of viral agents capable of causing hepatitis
Hepatitis A, B, C, D and E
Other viruses: Epstein Barr virus, cytomegalovirus
Compare the structure of a lobule to that of a hepatic acinus. Describe the directions of blood flow and bile flow.
Lobule - hexagonal in shape, with plates of hepatocytes that radiate outward from a central vein and portal tracts are found at each corner of the lobule
Hepatic Acinus - based on three zones corresponding to different degrees of oxygenation; kernel-shaped that is centred upon a portal tract
Blood flows from portal tract to central vein (via sinusoids); Bile flow from central areas to portal tracts (via bile canaliculi)
Outline the potential clinical features of cystic fibrosis
Pulmonary features
- mucous plugging and impaired mucociliary function
- recurrent infections and chronic inflammation (fibrosis)
Pancreatic features
- reduced or absent pancreatic enzymes
- malabsorption occurs due to impaired digestion
Biliary features
- cholestasis can result in secondary biliary cirrhosis and cholelithiasis
Reproductive features
- sub-fertility or infertility
Define the term porta hepatis. What structures pass through the porta hepatis?
Porta hepatis is a transverse fissure on the visceral surface of the liver, between the caudate and quadrate lobes
- portal vein
- hepatic artery
- hepatic nerve plexus
- hepatic ducts
- lymphatic vessels
How would you introduce the gall bladder (structure/function/location) in the setting of lab exam?
Structure: pear-shaped muscular sac 7-10cm in length, covered by peritoneum
Location: lies in the gall bladder fossa on the visceral surface of the liver
Function: storage and concentration of bile
Compare the two blood supplies of the liver (portal vein vs. hepatic artery)
Portal vein (70%) provides nutrient-rich blood supply from stomach and intestines Hepatic artery (30%) provides oxygen-rich blood supply
List the three types of jaundice and provide an example for each. Identify the aspect of bilirubin metabolism that is affected
Classification of jaundice is based on where bilirubin metabolism is affected:
Haemolytic jaundice
- due to excessive RBC destruction, which overwhelms the liver’s ability to form conjugated bilirubin (e.g. thalassaemia)
Hepatic jaundice
- due to impaired hepatocyte functions (such as impaired uptake or intracellular transport of bilirubin or reduced enzymatic activity) (e.g. drug toxicity or alcoholic hepatitis)
Cholestatic jaundice
- due to obstruction of intrahepatic or extrahepatic bile ducts (e.g. neoplasia)
How would you introduce the liver (structure/function/location) in the setting of a lab exam?
Structure: The liver is a large, complex organ divided into 4 irregular lobes
Location: located in the RUQ and LUQ of the abdomen, and is separated from the thoracic cavity by the diaphragm
Function: The liver is primarily involved in synthesis, detoxification, metabolism and storage, excretion and has an immune function.
List some risk factors that are associated with the formation of gallstones
- Adults < 40 years old, stones are more common in women
- obesity, increased age, multi-parity diabetes, diets high in refined sugar, ileal disease
Describe the mechanism by which chronic alcohol abuse causes liver damage
- alcohol causes induction of oxidases
- these enzymes aid metabolism but damage hepatocytes with chronic exposure
- liver damage is dose related
What are some osteopathic implications of viral hepatitis?
polyarthralgia affecting small joints may mimic a musculoskeletal complaint
must consider these findings in context of patient history
Summarise the different types and functions of pancreatic enzymes
Proteases digest proteins
Lipases digest emulsified fats
Amylase digests starch
Nucleases digest nucleic acids
Attachments or location of falciform ligament
Connects liver to anterior abdominal wall and diaphragm
Describe clinical features associated with each stage of alcohol-related liver damage
Stage 1: +/- hepatomegaly
Stage 2: tender hepatomegaly, fever, jaundice, ascites
Stage 3: ascites, splenomegaly, varicose veins, jaundice, RUQ pain
Attachments or location of left and right triangular ligaments
Right: situated at the right extremity of the bare area
Left: continuous with falciform ligament anteriorly
What is the structure of the biliary tree?
Bile entering the bile ducts eventually enters the left and right hepatic ducts
These drain into the left and right lobes of the liver
Then, unite to form the common hepatic duct
Common hepatic duct emerges with cystic duct of the gall bladder to form the bile duct
Hepatopancreatic ampulla is formed by the union of bile duct and major pancreatic duct
Identify where the digestive enzymes are found in the different regions of the GIT.
CHO digestion
- Salivary amylase (oral cavity, pharynx, oesophagus)
- Pancreatic amylases (lumen of SI)
- Disaccharidases (epithelium of SI - brush border)
Protein digestion
- pepsin (stomach)
- pancreatic trypsin and chymotrypsin and pancreatic carboxypeptidase (lumen of SI)
Nucleic acid digestion
- Pancreatic nucleases (lumen of SI)
- Nucleotidases, nucleosidases and phosphatases (epithelium of SI - brush border)
Fat digestion
- bile salts and pancreatic lipase (lumen of SI)
What causes (other than alcohol) can lead to cirrhosis?
Liver tumours
What are the functions of bile?
Digestion and absorption
- emulsification of large fat particles into small droplets
- this increases SA available for lipases to act upon the fat molecules
- bile salts and phospholipids interact with the breakdown products of fat digestion (forming micelles)
- micelles ‘ferry’ free fatty acids and monoglycerides to the intestinal mucosa for absorption
Excretion of waste products
- bilirubin and excess cholesterol
- pathologies that interfere with bilirubin excretion can result in jaundice
What type of gallstone is most common in Western countries?
Cholesterol gall stone
Attachments or location of ligamentum venosum
In the foetus, connects the left umbilical vein to the IVC (allows blood to bypass the liver)
List the risk factors for primary liver cancer
- cirrhosis, viral hepatitis (HBV, HCV)
- exposure to aflatoxins (produced by mould - agriculturalists at risk)
- male (sex)
Attachments or location of coronary ligament
Demarcates the bare area of the liver (where the liver is not covered by peritoneum)
Discuss the role that digestive enzymes play in the chemical breakdown of food
Digestion involves hydrolysis, where water is added to each molecular bond that has been broken
Digestive enzymes:
- are produced by various organs of the GIT
- act as organic catalysts (accelerate chemical reactions without appearing in the final product)
- each enzyme possess an active site for a specific substrate
- function optimally at a specific pH
- most are synthesised as zymogens (proenzymes)
Name the lobes of the liver
Right lobe, quadrate lobe, caudate lobe, left lobe,
Describe the surfaces of the liver. Are these surfaces covered by peritoneum?
Diaphragmatic surface
- smooth, dome-shaped and convex
- related to the concave, inferior aspect of the diaphgram
- covered with peritoneum, except posteriorly where the bare area of the liver lies in contact with the diaphragm
Visceral surface
- inferior and posterior aspect
- is covered with peritoneum, except near the gall bladder and porta hepatis
List the components of bile.
Bile pigments (bilirubin) Phospholipids Bile salts Cholesterol, triglycerides Electrolytes
Summarise the pathophysiology of cystic fibrosis
CFTR (gene) located on chromosome 7 codes for membrane-bound chloride channel
Affected chloride channels are non-responsive to intra-cellular signalling that would normally open the channel
Secretions of affected cells contain inadequate amounts of chloride and water
The abnormal secretions are viscid and are retained by the affected glands
Secretions that may be affected:
- pulmonary mucous
- pancreatic enzymes
- sweat
- bile
- reproductive secretions
What is the venous drainage of the liver?
Hepatic veins open into the IVC just inferior to the diaphragm
Discuss the pathophysiology associated with cholesterol stone formation
occurs when factors alter the ratio related to the solubility of cholesterol in bile (cholesterol : bile salts : phospholipids)
crystal forms when bile is supersaturated with cholesterol
Identify and describe the stages of alcoholic liver damage
Stage 1: fatty liver
- excessive alcohol can lead to destruction of rough ER in hepatocytes, which reduces the number of lipoproteins synthesised and secreted
- this causes cells to become swollen with lipids
- mild to moderate changes are reversible
Stage 2: alcoholic hepatitis
- usually superimposed on fatty liver
- hepatocyte necrosis induces the infiltration of inflammatory cells
Stage 3: liver cirrhosis
- irreversible
- regenerating hepatocytes do not comform to normal cytoarchitecture (nodules formation)
- structural changes obstruct nutrient flow (impaired hepatocyte function)
- death occurs due to complications (leading to hepatocellular failure, portal hypertension)
What is the most common form of primary liver tumour? What type of tissue does this tumour originate from?
Hepatocellular Carcinoma (Hepatoma) originate from epithelial cells
Define the term jaundice
Refers to the yellow appearance of the skin, sclerae and mucous membrane; it is an important sign of liver disease
Summarise the clinical features that might be associated with acute hepatitis
Stage 1: Preclinical
- asymptomatic, but virus actively replicating
- spread during this phase is a concern
Stage 2: Prodromal/Pre-icteric
- anorexia (loss of appetite), nausea, vomiting, malaise, headache
- mild fever, diarrhoea, upper abdominal discomfort
Stage 3: Icteric
- jaundice develops
- possibly tender hepatomegaly +/- splenomegaly
- HBV: polyarthralgia affecting small joints, skin rash
Stage 4: Convalescent
- symptoms subside over a course of several weeks
How would you introduce the pancreas (structure/function/location) in the setting of a lab exam?
Structure: elongated, tadpole-shaped gland that is ~15cm long
Location: found in the epigastric and left hypochondriac regions; transversely behind stomach, in between spleen and duodenum
Function: functions both as an exocrine and endocrine gland. For example, pancreatic enzymes assist in the chemical digestion of proteins, lipids and carbohydrates, whilst insulin produced by the pancreas helps to regulate blood glucose levels.
Indicate the specific function of each enzyme involved in chemical digestion.
CHO digestion
polysaccharides + salivary amylase = smaller polysaccharides or maltose
polysaccharides + pancreatic amylase = maltose and other disaccharides
disaccharides + dissacharidases = monosaccharides
Protein digestion
proteins + pepsin = small polypeptides
polypeptides + pancreatic trypsin and chymotrypsin = smaller polypeptides
small polypeptides + pancreatic carboxypeptidase = amino acids
amino acids or small peptides + dipeptidases, carboxypeptidase, and aminopeptidase = amino acids
Nucleic acid digestion
DNA or RNA + pancreatic nucleases = nucleotides
nucleotides + nucleotidases = nucleosides
nucleosides + nucleosidases and phosphatases = nitrogenous bases, sugars, phosphates
Fat digestion
fat globules + bile salts = fat droplets
fat droplets + pancreatic lipase = glycerol, fatty acids, glycerides
Which forms of cancer commonly metastasise to the liver?
lung, breast, GIT, skin (melanoma)
Name the cells located in the exocrine portion of the pancreas. What is their function?
Acinar cells - form the bulk of the pancreas; possess abundant rough ER and inactive enzymes (zymogen granules) and secrete enzyme-rich pancreatic juice into the ductal system
Ductal cells - secrete water and HCO3
Differentiate the terms digestion and absorption.
Digestion refers to the catabolic process that breaks down complex food molecules to monomers
whilst…
Absorption is the passage of digested end products from the lumen of the GIT through mucosal cells into the blood or lymph
