Liver, Pancreas, and Gall Bladder

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Notes on Liver

• The liver is the largest organ - 3 lbs - in the body.

It is surrounded by:

• CT capsule.

• Glisson's capsule composed primarily of collagen overlaid by mesothelium except at the "bare area" where the peritoneum reflects onto the diaphragm.

Hepatic Intraperitoneal Surfaces:

1. Diaphragmatic.

2. Visceral, in contact with viscera.

Lobes of the ;iver

• 2 main right & left lobes and 2 posterior lobes, the caudate & quadrate.

• Left sagittal fissure separated right & left lobes, fossa for IVC superiorly & fossa for gall bladder inferiorly.

• Porta hepatis is where structures enter & leave the liver.

• Hepatic duct.

• Portal vein.

• Hepatic artery.

• Lymphatics Nerves.

Blood Supply of the Liver

Dual blood supply:

• Celiac trunk gives off common hepatic artery which divides to the proper hepatic and supplies the liver with 25% of its blood ARTERIAL.

• 75% of the blood is VENOUS from the portal vein.

• Mainly from veins in the intestines & contains nutrients & wastes from the GI tract.

Liver Parenchyma

• Parenchyma is composed of hepatocytes of endodermal origin (diverticula of the alimentary tract).

• Stroma is composed of CT & circulatory elements of mesodermal origin.

Liver Models

• Liver architecture can be viewed from both anatomical & functional perspectives.

• Lamellae of parenchyma radiate out in spoke-like fashion from a central vein.

• A "classic" lobule is generally 6-sided with the central vein as the center and portal triads at the periphery.

• Blood enters a classic lobule from the portal triad containing a branch of the portal vein & hepatic artery.

• Blood flow is from the periphery to the center (central vein).

• A branch of the bile duct also occurs at the triad and flow is a special case but is from center to the periphery.

Portal Triad

Portal vein Hepatic artery Bile duct (string of pearls).

Liver Function Tests (LFTs):

Cholesterol, INR, albumin.

Liver Endothelium and Sinusoids

• Endothelium of the liver sinusoids is fenestrated.

• The fenestra are clustered as sieve plates.

• In the sinusoids arterial & venous blood mixes & flows to exit via the central vein.

• The perisinusoidal space of Disse is the gap between the sinusoidal endothelium and the hepatocyte.

• In the classic lobule, blood flow is from the periphery to the center.

• The sinusoidal is composed of fenestrated endothelium with sieve plates and policed by fixed macrophages of the monocyte- macrophage system called von Kupffer cells (develop from circulating monocytes).

• Fat storing cells of Ito are cells that also add structural support to the liver, in addition to reticular fibers.

• Von Kupffer to Hepatocyte Endothelium to cells store vitamin A, a fat-soluble precursor of the visual pigment, rhodopsin.

• Bile production is effected by hepatocyte exocrine secretion. Hepatocytes are arranged such that a furrow forms in the plasmalemma of contiguous cells & when they are apposed an intercellular cleft is produced, the bile canaliculus.

Bile Flow

• Secretion of bile is into the intercellular cleft, the bile canaliculus that is sealed by tight junctions.

• Bile canaliculi empty into the paraportal (periportal) ductule of Herring lined by cuboidal epithelium and thence to bile ducts with their "string of pearls" nuclear arrangement.

• Because blood stays in the sinusoids & bile is formed and delivered to canaliculi, blood & bile never mix.

• The periportal space of Mall is continuous with the perisinusoidal Space of Disse.

• Portal lobule is a triangular area that drains bile from 3 adjacent lobules into one portal triad.

• The peripheral points are the central veins, therefore blood flows from center to periphery.

• This model emphasizes the exocrine function of the liver, ie. bile production.

• Portal or liver acinus A diamond shaped area of 2 adjacent classic lobules.

• Top & bottom of diamond are central veins & lateral structures are portal tracts.

Portal Tracts

• The portal tracts send out side branches to each other (vascular backbone) & give rise to a series of tributaries that spread thruogh the region.

• There is a direct correlation between blood supply & liver metabolism, therefore the acinar concept explains the zonation or gradient of metabolic activity seen in the liver.

Zones of the Liver

Zone 1 - zone of permanent function:

• Oval area nearest vascular backbone.

• Receives the richest blood supply.

• In trauma, is the last to necrose & the first to regenerate.

Zone 2 - zone of varying activity:

• 2nd best blood supply.

Zone 3 - nearest the central vein:

• Lowest oxygen & most waste products.

• Most susceptible to pathological change.

NOTE: There are 3 domains: Adjacent to Disse Lateral Bile canaliculus

Function of Hepatocytes

Hepatocytes are Renaissance cells; this is their functionality:

• Many mitochondria (2,000/cell).

• MV in Disse absorb plasma materials.

• Bile canaliculi sealed by tight junctions.

• Gap junctions common.

• SER can proliferate to detoxify substances.

• Glycogen stores.

• Abundant peroxisomes.

Functions of Liver

1. Serves as an interface between the blood & digestive system.

2. Synthesizes proteins for its on use.

3. Secretes plasma proteins & lipoproteins into the blood.

4. Hemopoiesis in the embryo.

5. Hepatocyte SER involved in detoxification of both endogenous & exogenous compounds.

6. Exocrine bile secretion of electrolytes bile acids phospholipids cholesterol bilirubin About 90% of these substances are derived from absorption from the intestine & transported from the blood to bile canaliculi by hepatocytes. 10% are synthesized by the hepatocyte.

7. Glycogen synthesis & glucose secretion. Transports glucose from blood to hepatocytes & stores it as glycogen. When blood glucose drops, hepatocytes hydrolyze glycogen (glycogenolysis) into glucose & delivers it to the space of Disse. Can also synthesize glucose (gluconeogenesis).

8. Produces plasma proteins for export: albumin prothrombin fibrinogen lipoproteins Hepatocytes do not store secretions as granules but continuously release them into the blood. 5% of protein exported is from von Kupffer cells.

9. Vitamin storage

10. Regeneration. Rats can have 75% of the liver removed and regenerate all of it in 1 month. This capacity is restricted in humans.

Cirrhosis

• Regenerated liver is usually normal but if there is repeated or continuous damage there is abundant production of CT that results in disorganization of liver tissue.

• The CT takes up space of the hepatocytes & disorganizes the vascular & bile systems.

Bilirubin Function and Flow

• Bilirubin is a breakdown product of hemoglobin processed by von Kupffer cells & other macrophages (spleen).

• Bilirubin is transported to hepatocytes & this water-insoluble compound is modified in the SER to a water-soluble form that is secreted into the bile canaliculi.

• When this material is not eliminated several diseases characterized by jaundice occur. Jaundice is a syndrome characterized by deposition of bile pigment in the skin & mucous membranes causing yellow pigmentation.

• Neonatal hyperbilirubinemia is caused by undeveloped SER in newborns. Exposure to blue light of fluorescent tubes transforms the compound to a form that can be excreted.

Jaundice

• One of the most common causes of jaundice are gallstones, unrelated to hepatocyte function, that obstruct bile flow.

• Gallstones are more common in females & most frequently occur in the 4th decade.

• Occurs in 20% females & 8% males. 80% of gallstones are composed of cholesterol (cholesterol stones 1-3 cm).

• 20% are pigment stones formed from the calcium salt of bile.

Notes on Pancreas

Pancreatic parts & ducts

• Head.

• Body.

• Tail.

• Uncinate process, behind Duct of Wirsung (main) Duct of Santorini (accessory).

• Ampulla of Vater.

Facts on Pancreas

2nd largest GI gland.

• Both endocrine & exocrine.

• Forms from endodermal diverticula of gut.

• Thin layer of CT & lobulated.

• Retroperitoneal except the tail which is intraperitoneal.

• Endocrine function mediated by islets of Langerhans.

• Exocrine function mediated by pancreatic acini.

Pancreatic Cells

5 major cell types: alpha, beta & delta cells connected by gap junctions, therefore are functionally integrated.

Diabetes Mellitus

A hyperglycemic metabolic disorder that results from lack of insulin or a defect in insulin receptors on target cells.

Type I Diabetes Mellitus:

• Juvenile onset & insulin dependent.

• A pancreas problem, just don't make insulin.

Type II Diabetes Mellitus:

• Most common, non-insulin dependent, generally affects individuals over 40.

• Lose weight, give large quantities of insulin or give other hypoglycemic medications.

• 3 signs: polydipsia - constant thirst polyphagia - constant hunger polyuria - excessive urination

Pancreatic Acini and Enzymes

• Acini produce a variety of digestive enzymes in an alkaline medium and deliver them to the duct system & thence to the duodenum.

• Pancreatic enzymes degrade protein, carbohydrate & lipids.

• Pancreatic enzymes are produced in an inactive form and are activated in the duodenum.

• Trypsin, the most common enzyme, is produced as inactive trypsinogen.

• The cytoplasm of acinar cells also have a trypsin inhibitor produced concurrently with the digestive enzymes.

• If these mechanisms fail, acute pancreatitis can occur in which the enzymes are activated & the pancreas is digested by its own enzymes.

• Some enzymes produced: trypsinogen chymotrypsinogen ribonuclease amylase etc.

Pancreatic Cells

• Centroacinar cells are the proximal most part of the duct system.

• Project into the lumen.

• Produce alkaline fluid which helps buffer the acid chyme in the duodenum.

• Duct cells are initially cuboidal but become columnar and stratified in progressively larger ducts.

• Enteroendocrine cells of duodenum assist the pancreas.

• Secretin produces a fluid rich in bicarbonate ions that help neutralize the acidity of chyme.

• Cholecystokinin (CCK) promotes motility of the gall bladder.

• Enteroendocrine cells scattered throughout the GI tract and its derivatives produce numerous hormones that act as a balanced system of agonists & antagonists that collectively regulate & coordinate most aspects of GI activity in concert with the ANS.

• Secreted substances include: serotonin somatostatin motilin bombesin enteroglucagon substance P gastric inhibitory polypeptide gastrin.

Notes on Gall Bladder

General Anatomy

• Hollow pear-shaped.

• Stores 30-50 ml.

• Cystic duct connects to common hepatic duct to form the common bile duct which joins the common pancreatic duct to form the hepatopancreatic ampulla (ampulla of Vater) which opens to the duodenum at the major duodenal papilla through the sphincter of Oddi.

• Spiral valve of Heister in cystic duct passively slows down the transport of bile.

The general layering seen elsewhere in the GI tract is modified in the gall bladder. Epithelium is simple columnar mucous.

• Mucosa - epithelium & lamina propria.

• Muscular lamina - comparable to muscularis externa.

• Perimuscular layer with vessels & CT.

• Serosa Rokitansky-Aschoff sinuses are mucosal diverticula. Can be inflamed by bacteria.

• Luschka ducts do not open to the lumen, considered aberrant embryonic bile ducts.

Functions

1. Bile reservoir.

2. Concentrates bile.

Bile Concentration and Secretion

• Active sodium pump moves sodium out and Cl- follows and water follows, thus concentrating the bile.

• The stimulus of lipid in the small intestine causes cholecystokinin to be released by enteroendocrine cells of the duodenum which stimulates the gall bladder to contract.

• Bile secretions emulsify lipid.

GI Clinical Correlations

• Jaw-jerk reflex - proprioceptive fibers in periodontal ligament causes an involuntary opening of the jaw when biting down on a hard object.

• The bacterium Vibrio cholerae (passed in drinking water) releases cholera toxin that greatly increases secretion by Brunner's glands.

• Fluid loss may be 10 liters/day.

• If not replaced may lead to circulatory shock.

• Fluid loss is accompanied by electrolyte loss, a contributory factor to death.

• Peristaltic rush - if intestinal mucosa is subjected to profound irritation, the muscularis externa may undergo intense & swift contractions for prolonged periods.

• Can propel chyme into the colon in a matter of minutes for elimination as diarrhea.

Rectal Examination in Males Reveals

• Bulb of penis.

• Prostate enlarged.

• Seminal vesicles.

• Inferior part of distended bladder.

• Enlarged iliac lymph nodes.

Rectal Examination in Females Reveals

• Pathological cervix.

• Ovaries.

• Broad ligament.

Appendicitis

• Inflammation of the appendix.

• Incidence greater in teenagers & young adults if not treated within 1-2 days may rupture causing peritonitis & death.

Mumps

• Mumps are caused by a viral infection and affects the parotid, ovaries & testes.

• May result in sterility in adults.

Pancreatic Cancer

• Fifth leading cause of mortality from all cancers. Less than 50% diagnosed survive more than 1 year and fewer than 5% survive 5 years.

• Cigarette smokers have a 70% greater risk.

Additional Reading:

Basic Histology

1. Introduction to Histology
2. Basic Cell Physiology
3. Actin, Microtubules, and Intermediate Filaments
4. Mitochondria, Nucleus, Endoplasmic Reticulum, Golgi
5. Epithelium (Epithelial Tissue)
6. Connective and Adipose Tissue
7. Types of Cartilage
8. Osteogenesis
9. Nervous Tissue
10. Muscle Tissue
11. Cardiovascular System
12. Blood and Hematopoiesis
13. Lymphoid Tissue
14. Digestive Tract I: Oral Cavity
15. Digestive Tract II: Esophagus through Intestines
16. Liver, Pancreas, and Gall Bladder
17. Respiratory System
18. Integument
19. Urinary System
20. Endocrine System
21. Male Reproductive System
22. Female Reproductive System
23. Eye and Ear

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