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Gallbladder and Biliary Tract: Anatomy

The gallbladder is a pear-shaped sac, located directly beneath the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, that sits on top of the superior part of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Bile is secreted by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy into thin channels Channels The Cell: Cell Membrane called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules Lobules Breasts: Anatomy. The bile leaves the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy via the right and left hepatic ducts, which join together to form the common hepatic duct. The common hepatic duct joins with the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis to form the common bile duct, which empties into the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy. If the sphincters leading into the intestines are closed, bile will travel via the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis into the gallbladder for storage.

Last updated: Apr 4, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Development

  • The gallbladder and biliary tree begin to develop in the 3rd–4th weeks of gestation.
  • Derived from endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation
  • Hepatic diverticulum Diverticulum A pouch or sac opening from the colon. Diverticular Disease (sometimes called the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy bud): 

Gross Anatomy of the Gallbladder

Location

  • In the RUQ of the abdomen
  • Immediately under the right lobe of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy in the gallbladder fossa
  • Connected to the visceral surface of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy via the cystic Cystic Fibrocystic Change plate
  • Sits on top of the superior part of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
Anatomic relationships of the pancreas to surrounding organs

Anatomic relationships of the gallbladder to surrounding organs:
Note that the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy are light gray and that the intestines have been removed completely in order to allow better visualization of this posterior organ.

Image by BioDigital, edited by Lecturio

Structure of the gallbladder

  • Shape: pear-shaped sac
  • Size:
    • 7–10 cm long
    • 4–5 cm wide
    • Volume: approximately 50 mL
  • Fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy:
    • Rounded base of the organ
    • Usually projects slightly beyond the inferior margin of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Body: 
    • Main portion of the organ
    • In direct contact with:
      • Visceral surface of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
      • Superior part of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
  • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess: 
    • Typically makes an S-shaped bend
    • Empties into the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis 
    • Spiral Spiral Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) valves (of Heister): 
      • Undulating folds or valves in the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis
      • Keep the duct open so bile can easily be diverted into the gallbladder when distal sphincters are closed
      • Helps prevent dumping of bile into the intestines during sudden increases in intraabdominal pressure (e.g., coughing) when sphincters are closed
Gallbladder

Location and basic anatomy of the gallbladder and major biliary ducts

Image: “The gallbladder stores and concentrates bile, and releases it into the two-way cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis when it is needed by the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy” by OpenStax College. License: CC BY 4.0

Gross Anatomy of the Biliary Tree

Bile, a digestive fluid produced and secreted by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, is transported to the gallbladder and small intestines by a series of branching bile ducts known collectively as the biliary tree.

Intrahepatic bile ducts

Ducts that originate within the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy itself are known as intrahepatic bile ducts and can be divided into:

  • Bile canaliculi: 
    • Narrow channels Channels The Cell: Cell Membrane located between sheets of hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy within hepatic lobules Lobules Breasts: Anatomy (hexagon-shaped functional units in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy)
    • Drain into bile ductules at the exterior of the hepatic lobule
  • Bile ductules (also called interlobular bile ducts): 
    • Part of the portal triads located at the “corners” of each hepatic lobule, which contain:
      • Hepatic arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology
      • Portal venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology
      • Bile ductules 
    • Ultimately drain into the right or left hepatic ducts
  • Hepatic ducts:
    • Intrahepatic and extrahepatic segments
    • Right hepatic duct: drains the right lobe of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy 
    • Left hepatic duct: drains the left lobe of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
Microscopic_anatomy_of_liver

Microscopic anatomy of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy:
Bile is produced in the hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy and secreted into the bile canaliculi. These canaliculi drain into the bile ductules (located next to the portal arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology and venules Venules The minute vessels that collect blood from the capillary plexuses and join together to form veins. Veins: Histology). The bile ductules ultimately drain into the right and left hepatic ducts.

Image: “The liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy receives oxygenated blood from the hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy and nutrient-rich deoxygenated blood from the hepatic portal Hepatic portal Liver: Anatomy vein” by OpenStax College. License: CC BY 4.0

Extrahepatic bile ducts

Extrahepatic bile ducts are located outside the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and are continuous with the intrahepatic bile ducts. There are many normal anatomic variants. These ducts include:

  • Extrahepatic segments of the right and left hepatic ducts
  • Common hepatic duct: formed via the combination of the right and left hepatic ducts
  • Cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis
    • Outflow tract of the gallbladder
    • Approximately 7 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma in diameter
    • Contains valves of Heister
    • Many normal anatomic variants
  • Common bile duct: 
    • Formed via the combination of the common hepatic duct and the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis
    • Size:
      • Approximately 6 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma in diameter
      • Approximately 6–8 cm in length
    • Runs posterior to the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy 
    • Runs through the head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, where it joins with the main pancreatic duct Main pancreatic duct Pancreas: Anatomy to form a swelling Swelling Inflammation called the hepatopancreatic ampulla (also known as the ampulla of Vater)
      • Located within the head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, just prior to its insertion into the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
      • Empties into the descending part of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy via an opening called the major duodenal papilla
      • Contains the hepatopancreatic sphincter (also known as the sphincter of Oddi): controls release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of bile and pancreatic juice Pancreatic Juice The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. Pancreas: Anatomy

Microscopic Anatomy

There are 3 primary layers in the wall of the gallbladder (from internal to external):

  • Mucosa: 
    • Contains ridges/folds that flatten when gallbladder fills/distends 
    • Simple columnar epithelial cells:
      • Line the lumen of the gallbladder
      • Contain Na+-ATP pumps to help concentrate bile
      • Connected to one another via tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions
      • Intercellular space: clear spaces between epithelial cells where water is being absorbed (unable to move back into the lumen due to tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions)
    • Lamina propria Lamina propria Whipple’s Disease
      • Collagenous connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
      • Contains blood vessels 
  • Muscularis externa: 
  • Serosa:
    • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology layer
    • Merges with the Glisson capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy 
  • Differences between gallbladder wall and other intestinal lumens:
    • No muscularis mucosa (within the mucosal layer)
    • No submucosal layer
    • Muscularis externa is much thinner
  • Bile ducts have the same structure as the gallbladder (except bile canaliculi lumen, which are lined by the apical poles of hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy, no epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology)
Histologic slide depicting gallbladder and mucosal folds

1) Histologic slide depicting the 3 layers of the gallbladder, in addition to the lumen and neighboring hepatic tissue
2) Histologic slide depicting the mucosal folds and ridges, as well as the thin layer of smooth muscle found in the gallbladder

Image by Geoffrey Meyer, PhD.

Related videos

Neurovasculature

Blood and lymphatics

  • Arterial blood supply: 
    • Gallbladder: Cystic Cystic Fibrocystic Change artery, which most commonly arises from the right hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy 
    • Hepatic ducts: branches of the hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy
    • Retroduodenal portion of the common bile duct: 
      • Posterior superior pancreaticoduodenal artery 
      • Gastroduodenal artery
  • Venous drainage: 
    • Body and fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy of gallbladder: small veins Small veins Veins: Histology that empty into the hepatic sinusoids Sinusoids Liver: Anatomy
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis: cystic Cystic Fibrocystic Change veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy 
    • Hepatic and common bile duct: posterior superior pancreaticoduodenal vein → portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy
  • Lymphatic drainage: cystic Cystic Fibrocystic Change lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy → hepatic nodes→ celiac nodes
Liver irrigation

Overview of the abdominal arterial blood supply:
The celiac trunk is the 1st major branch of the abdominal aorta Abdominal Aorta The aorta from the diaphragm to the bifurcation into the right and left common iliac arteries. Posterior Abdominal Wall: Anatomy. The trunk supplies the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy and parts of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy and duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy with oxygenated blood.
The celiac trunk gives off the left gastric artery Gastric artery Any of several branches of the splenic artery distributed to the greater curvature of the stomach. Stomach: Anatomy, splenic artery, and the common hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy. The common hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy divides into the hepatic artery Hepatic artery A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. Liver: Anatomy proper, the gastroduodenal artery, and the right gastric artery Gastric artery Any of several branches of the splenic artery distributed to the greater curvature of the stomach. Stomach: Anatomy, all of which can be seen here.

Image by Lecturio.

Innervation

The gallbladder and biliary tree are primarily innervated by 3 nerves/complexes:

  • Celiac nerve plexus: 
    • Sympathetic fibers ( trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation bile storage)
      • Relaxation of the gallbladder
      • Contraction of sphincter muscles
    • Visceral afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology fibers → pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways sensation
  • Vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy: parasympathetic fibers ( trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation bile release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology)
    • Contraction of the gallbladder
    • Relaxation of sphincter muscles
  • Right phrenic nerve Phrenic nerve The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm. Diaphragm: Anatomy: sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology somatic afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology fibers

Functions of the Gallbladder and Bile

Functions of the gallbladder

  • Storage of bile:
    • 40–50 mL in normal conditions 
    • Up to 300 mL in cases of biliary obstruction
  • Concentration of bile: 
    • Mucosal Na+-ATP pumps divert Na+ from the bile into the lamina propria Lamina propria Whipple’s Disease.
    • Water follows the Na+ into the lamina propria Lamina propria Whipple’s Disease (is unable to move back into the gallbladder lumen because of the tight occluding junctions at the surface)
    • Results in concentration of bile within the lumen
  • Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of bile: muscular layer contracts to release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology bile into the intestinal lumen when needed

Bile

Bile is a dark green-yellowish brown fluid produced by the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy

  • Composition: 
    • 97% water
    • 0.7% bile salts Bile salts Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. Cholelithiasis: critical for emulsification Emulsification Gastrointestinal Secretions of fats Fats The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (dietary fats) as a source of energy. Energy Homeostasis
    • 0.5% fats Fats The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (dietary fats) as a source of energy. Energy Homeostasis, including:
      • Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism: for excretion
      • Phospholipids Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Lipid Metabolism: critical for emulsification Emulsification Gastrointestinal Secretions 
    • 0.2% bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism
      • Primary pigment responsible for the color of bile (and ultimately stool)
      • Waste product Product A molecule created by the enzymatic reaction. Basics of Enzymes from the breakdown of old/damaged RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy
  • Functions: 
    • Emulsion and absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids 
    • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of the fat-soluble substances, such as vitamins A, D, E, and K
    • Excretion of bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism and cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism
    • Bile salts Bile salts Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. Cholelithiasis stimulate bowel movement.
    • Helps neutralize the hydrochloric acid Hydrochloric acid A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. Caustic Ingestion (Cleaning Products) entering the intestine from the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy ( pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance of bile: 7.6–8.6) 
    • Antiseptic action against microorganisms present in food
  • Basic physiology:
    • Cholecystokinin Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Gastrointestinal Secretions:
      • GI hormone that is released when fatty chyme Chyme Small Intestine: Anatomy enters the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
      • Causes contraction of the gallbladder and relaxation of the sphincter of Oddi
    • Hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy produce about 500–1000 mL of bile per day
    • Bile acids Bile acids Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. Short Bowel Syndrome are reabsorbed in the ileum Ileum The distal and narrowest portion of the small intestine, between the jejunum and the ileocecal valve of the large intestine. Small Intestine: Anatomy portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy (enterohepatic circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment)

Clinical Relevance

  • Cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis: presence of stones in the gallbladder. The stones are predominantly of the cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism type, while the rest are composed of bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism (pigment stones) and other mixed components. Individuals are commonly asymptomatic but may present with biliary colic (intermittent pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the RUQ, usually after a fatty meal); the pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is caused by gallbladder contractions around the stones. The diagnosis is established by ultrasonography. 
  • Porcelain gallbladder Porcelain Gallbladder Cholelithiasis: chronic gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis irritate the gallbladder wall, leading to extensive calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes deposition and brittle, hard walls. Porcelain gallbladder Porcelain Gallbladder Cholelithiasis carries an increased risk of gallbladder adenocarcinoma. 
  • Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the gallbladder usually resulting from obstruction of the cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis by a gallstone. Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis presents with RUQ abdominal pain Abdominal Pain Acute Abdomen, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus. The diagnosis is usually made clinically and confirmed via ultrasonography. Management is usually surgical ( cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy).
  • Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis: life-threatening condition that develops as a result of stasis and infection of the biliary tract. Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis is characterized by fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, and abdominal pain Abdominal Pain Acute Abdomen. Septic shock Septic shock Sepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status. Sepsis and Septic Shock, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease, and multiorgan dysfunction are potential serious complications. 
  • Primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis: chronic inflammatory condition that is characterized by fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and stricture Stricture Primary Sclerosing Cholangitis of the biliary ductal system. Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor is with an insidious onset of fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), and jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, which can progress to cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and complications related to biliary obstruction. The exact etiology is unknown, but there is a strong association with inflammatory bowel disease. 
  • Primary biliary cirrhosis Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis: chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor is that of a middle-aged woman presenting with pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, and RUQ abdominal pain Abdominal Pain Acute Abdomen. Slow damage to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tissue can lead to scarring Scarring Inflammation, fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, and eventually cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis.
  • Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors:  type of cancer that forms in the bile ducts. The risk factors include primary sclerosing cholangitis Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is an inflammatory disease that causes fibrosis and strictures of the bile ducts. The exact etiology is unknown, but there is a strong association with IBD. Patients typically present with an insidious onset of fatigue, pruritus, and jaundice, which can progress to cirrhosis and complications related to biliary obstruction. Primary Sclerosing Cholangitis, hepatolithiasis Hepatolithiasis Rare Malignant Liver Tumors, cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C, and certain liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy flukes. Cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors presents with jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), abdominal pain Abdominal Pain Acute Abdomen, clay-colored stools, and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice: abnormal yellowing of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and/or sclera Sclera The white, opaque, fibrous, outer tunic of the eyeball, covering it entirely excepting the segment covered anteriorly by the cornea. It is essentially avascular but contains apertures for vessels, lymphatics, and nerves. Eye: Anatomy caused by the accumulation of bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism. Bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism is excreted in the bile, so abnormal biliary excretion can lead to jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice. Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice can be clinically appreciated when the serum bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism levels rise to > 2–3 mg/dL. 

References

  1. Hundt M, Wu CY, Young M. (2021). Anatomy, abdomen and pelvis, biliary ducts. StatPearls. Retrieved August 28, 2021, from  https://www.ncbi.nlm.nih.gov/books/NBK459246/
  2. Jones M, Hannoodee S. (2021). Anatomy, abdomen and pelvis, gallbladder. StatPearls. Retrieved August 28, 2021, from https://www.statpearls.com/ArticleLibrary/viewarticle/32113
  3. Drake RL, Vogl AW, Adam Mitchell WM. (2020). Gray’s Anatomy for students, 4th ed. Churchill Livingstone/Elsevier. 
  4. Moore KL, Dalley AF,& Agur, A. M. R. (2014). Clinically Oriented Anatomy (7th ed.). Lippincott Williams & Wilkins, a Wolters Kluwer business.

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