Hormones and accessory organs of GIT (berne Ch. 31; guyton Ch. 64) Flashcards
Serves as the first site of processing for most absorbed nutrients
Liver
A metabolic powerhouse, critical for disposing of a variety of metabolic waste products and xenobiotics from the body by converting them to forms that can be excreted
Liver
“Glucose buffer function of the liver”
The liver stores glucose as glycogen at times of glucose excess (such as in the postprandial period) and then releases stored glucose into the bloodstream as it is needed
Protein that determines plasma oncotic pressure
Albumin
What are the levels at which the liver removes and metabolizes/detoxifies substances originating from the portal circulation? (2)
Physical – Blood arriving in the liver percolates among cells of macrophage lineage, known as Kupffer cells
Biochemical – Hepatocytes are endowed with a broad array of enzymes that metabolize and modify both endogenous and exogenous toxins so that the products are, in general, more water soluble and less susceptible to reuptake by the intestine.
What are the two classes of biochemical degradation of substances in the liver?
Phase I reactions (oxidation, hydroxylation, and other reactions catalyzed by cytochrome P-450 enzymes)
phase II reactions that conjugate the resulting products with another molecule, such as glucuronic acid, sulfate, amino acids, or glutathione, to promote their excretion
Key transporters of hepatocytes Name: NTCP Basolateral: Canalicular: Substrate/Function:
Name: NTCP
Basolateral: Yes
Canalicular: No
Substrate/Function: Uptake of conjugated bile acids
Key transporters of hepatocytes Name: OATP Basolateral: Canalicular: Substrate/Function:
Name: OATP
Basolateral: Yes
Canalicular: No
Substrate/Function: Uptake of bile acids and xenobiotics
Key transporters of hepatocytes Name: BSEP Basolateral: Canalicular: Substrate/Function:
Name: BSEP
Basolateral: No
Canalicular: Yes
Substrate/Function: Secretion of conjugated bile acids
Key transporters of hepatocytes Name: MDR3 Basolateral: Canalicular: Substrate/Function:
Name: MDR3
Basolateral: No
Canalicular: Yes
Substrate/Function: Secretion of phosphatidylcholine
Key transporters of hepatocytes Name: MDR1 Basolateral: Canalicular: Substrate/Function:
Name: MDR1
Basolateral: No
Canalicular: Yes
Substrate/Function: Secretion of cationic xenobiotics
Key transporters of hepatocytes Name: ABC5/ABC8 Basolateral: Canalicular: Substrate/Function:
Name: ABC5/ABC8
Basolateral: No
Canalicular: Yes
Substrate/Function: Secretion of cholesterol
Key transporters of hepatocytes Name: cMOAT/MRP2 Basolateral: Canalicular: Substrate/Function:
Name: cMOAT/MRP2
Basolateral: No
Canalicular: Yes
Substrate/Function: Secretion of sulfated lithocholic acid and conjugated bilirubin
Blood flow through the liver can increase considerably without a concomitant increase in pressure. This feature of the liver is due to what structure?
Low-resistance sinusoids
What vessel supplies the sinusoids?
Hepatic artery and portal vein
Hepatic endothelial cells contain specialized openings that are large enough to permit the passage of molecules as big as albumin
Fenestrations
Separating the endothelium from the hepatocytes is a thin connective tissue layer of loose connective tissue called ______
Space of Disse
IN THE CLINIC
If the circulation of the liver, particularly its sinusoids, is compressed by fibrosis, the liver loses its ability to accommodate the increases in blood flow that occurs after a meal without a concomitant increase in pressure. Because of the fenestrations, albumin escapes from the circulation and albumin-rich fl uid weeps from the surface of the liver into the abdominal cavity, where it overwhelms the lymphatic drainage. This condition is known as _______
Ascites
IN THE CLINIC
Infection of the liver with certain viruses or over exposure to toxic substances such as alcohol kills hepatocytes and activates hepatic stellate cells, which synthesize excessive amounts of collagen that result in the histologic appearance of fibrosis. If the insult is chronic, the fibrosis eventually becomes irreversible, a condition known as
Cirrhosis
Cells that serve as storage sites for retinoids and in addition are the source of key growth factors for hepatocytes
Stellate cells
**Under abnormal conditions, stellate cells are activated to synthesize large quantities of collagen, which contributes to the hepatic dysfunction.
Classic columnar epithelial cells that line biliary ductules
Cholangiocytes
In the liver, the apical surface of the hepatocyte occupies only a small fraction of the cell membrane, and the apical membranes of adjacent cells oppose each other to form a channel between the cells known as _______
Canaliculus
The biliary ductules drain into large bile ducts that coalesce into what structure?
Right and left hepatic ducts
Bile can flow into the gallbladder via what duct?
Cystic duct
Bile can flow to t he intestine via what duct?
Common bile duct
Hepatic triad
Hepatic vein, hepatic artery and bile duct
Hepatocytes lying closest to the hepatic triad are referred to as periportal, and have the greatest supply of oxygen and nutrients
Zone 1 cells
The majority of bile fl ow is driven by the secretion of bile acids across the apical membrane of hepatocytes via an ATPase transporter known as _____
Bile Salt Export Pump (BSEP)
Bile acids are produced by hepatocytes as end products of what metabolism?
Cholesterol metabolism
Rate-limiting step in bile acid synthesis
Addition of a hydroxyl group to the 7 position of the steroid nucleus by the enzyme cholesterol 7a-hydroxylase
Primary bile acids
Chenodeoxycholic acid and cholic acid
A mechanism causes a change in bile acid that makes it unable to passively traverse the cell membranes of the small intestine. What is this mechanism?
Conjugation of bile acid
**Conjugated bile acids are almost totally ionized at the pH prevailing in the small intestinal lumen and thus cannot passively traverse cell membranes
Conjugated bile acids are retained in the intestinal lumen until they are actively absorbed in the terminal ileum via what transporter?
Apical sodium-dependent bile salt transporter (ASBT)
This secondary bile acid is preferentially sulfated in the hepatocytes rather than reconjugated with taurine or glycine
Lithocolic acid
Phosphatidylcholine derives from the inner leaflet of the canalicular membrane and is specifi cally “fl ipped” across the membrane by another ABC family transporter called ____
Multidrug resistance protein 3 (MDR3)
True or false
Mixed micelles composed of bile acids, phosphatidylcholine, and cholesterol are osmotically active
True
**Because micelles composed of bile acid, p phosphatidylcholine, and cholesterol in the bile canaliculus are osmotically active and tight junctions that link hepatocytes are leaky; water is drawn into the canalicular lumen, as well as other plasma solutes, such as Ca, glucose, glutathione, amino acids, and urea.
Responsible for the modification of bile secretion
Cholangiocytes lining the biliary ductules
In bile acid modification, glucose and amino acids are (a) absorbed (b) secreted
a. Absorbed
Glutathione is broken down on the surface of cholangiocytes into its constituent amino acids by what enzyme?
γ-glutamyl transpeptidase (GGT)
Muscular sac lined with highresistance epithelial cells
Gallbladder
IN THE CLINIC
Humans are unusually susceptible to gallstones. What mechanism is defective in susceptible individuals?
Antinucleating proteins
- *cholesterol is supersaturated in the bile of many adults, with precipitation normally being inhibited by the presence of antinucleating proteins
- *storage of bile in the gallbladder (in period between meals or fasting) increases its concentration
- Prolonged storage of bile increases the chance that nucleation can occur thus prolonged fasting increases the risk for gallstones
Bilirubin is synthesized by what system?
Reticuloendothelial system (macrophages) – Kupffer cells and macrophages in the spleen ** The enzyme heme oxygenase that is present in these cells liberates iron from the heme molecule and produces the green pigment biliverdin
Bilirubin is essentially insoluble in aqueous solutions at neutral pH. It is transported through the bloodstream bound to albumin. When this complex reaches the liver, it enters the space of Disse, where bilirubin is selectively taken up across the basolateral membrane of hepatocytes via what transporter?
OATP transporter
** The bilirubin conjugates are then secreted into bile by a multidrug-related protein (MRP2) located in the canalicular membrane
IN THE CLINIC
A condition associated with mutations in the hepatocyte enzyme UGT thus impairs the ability of hepatocytes to conjugate bilirubin
Crigler-Najjar syndrome
** In type I Crigler-Najjar syndrome, a congenital missense mutation results in complete lack of this enzyme, whereas patients with type II Crigler-Najjar syndrome have a milder mutation that reduces UGT levels to about 10% of those seen in normal individuals.
The liver eliminates ammonia from the body by converting it to urea via a series of enzymatic reactions known as ____
Urea/ Krebs-Henseleit cycle
Salivary secretion is a two-stage operation: the first stage involves the _____, and the second, the _____
Acini, salivary ducts
The acini secrete what kind of secretion that contains ptyalin and/or mucin in a solution of ions in concentrations not greatly different from those of typical extracellular fluid?
Primary secretion
As the primary secretion flows through the ducts, what two major active transport processes take place that markedly modify the ionic composition of the fluid in the saliva?
- Sodium ions are actively reabsorbed from all salivary ducts and potassium ions are actively secreted in exchange for the sodium
- Bicarbonate ions are secreted by the ductal epithelium into the lumen of the duct. This is at least partly caused by passive exchange of bicarbonate for chloride ions
The salivatory nuclei are located approximately at the juncture of the _____
Pons and Medulla
Secreted by the activated salivary cells, which in turn acts as an enzyme to split one of the blood proteins, an alpha2-globulin, to form bradykinin, a strong vasodilator
Kallikrein
The main body of the esophagus is primarily lined by _____
Simple mucous glands
The gastric end and to a lesser extent in the initial portion of the esophagus is primarily lined by ____
Compound mucous glands
The oxyntic (acid-forming) glands secrete _____
Hydrochloric acid, pepsinogen, intrinsic factor, and mucus
The oxyntic glands are located on the inside surfaces of ______ the stomach. The pyloric glands are located in the ______ of the stomach
Body or fundus, antrum portion
IN THE PARIETAL CELL
These two effects together create a negative potential of -40 to -70 millivolts in the canaliculus, which in turn causes diffusion of positively charged potassium ions and a small number of sodium ions from the cell cytoplasm into the canaliculus
- Chloride ion is actively transported from the cytoplasm of the parietal cell into the lumen of the canaliculu
- Sodium ions are actively transported out of the canaliculus into the cytoplasm of the parietal cell
IN THE PARIETAL CELL
Water becomes dissociated into hydrogen ions and hydroxyl ions in the cell cytoplasm. What is the fate of the hydrogen ions? What is the fate of hydroxyl ions?
The hydrogen ions are then actively secreted into the canaliculus exchange for potassium ions; Hydroxyl ions bind with CO2 to form bicarbonate and diffuse out of the cell cytoplasm into the extracellular fluid in exchange for chloride ions that enter the cell from the extracellular fluid
When the acid-producing parietal cells of the stomach are destroyed, which frequently occurs in chronic gastritis, the person develops (2) _____
- achlorhydria (lack of stomach acid secretion)
- pernicious anemia because of failure of maturation of the red blood cells in the absence of vitamin B12 stimulation of the bone marrow
The entire surface of the stomach mucosa between glands has a continuous layer of a special type of mucous cells that secretes alkaline fluid containing mucin which serves to protect the stomach wall and for lubrication
Surface mucous cells – this is different from mucous neck cells where the secretion is less alkaline.
The presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factor in the upper small intestine causes release of several intestinal hormones. One of these hormones is especially important for control of pancreatic secretion
Secretin
3 basic stimuli that cause pancreatic secretion
- Acetylcholine, which is released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system
- Cholecystokinin, which is secreted by the duodenal and upper jejunal mucosa when food enters the small intestine
- Secretin, which is also secreted by the duodenal and jejunal mucosa when highly acid food enters the small intestine
When bile is stored in the gallbladder, its cholesterol, lecithin, and bilirubin concentration increases by as much as 5 to 20-fold, how is this achieved?
Water, sodium, chloride, and most other small electrolytes are continually absorbed through the gallbladder mucosa
Gallbladder absorption is caused by what transport mechanisms?
Active transport of sodium through the gallbladder epithelium, and this is followed by secondary absorption of chloride ions, water, and most other diffusible constituents
Bile is secreted in two stages by the liver. The initial portion is secreted by what principal functional cells of the liver?
Hepatocytes
** This initial secretion contains large amounts of bile acids, cholesterol, and other organic constituents. It is secreted into minute bile canaliculi that originate between the hepatic cells
In the second stage of bile secretion, the bile flows in the canaliculi toward what structure?
Interlobular septa, where the canaliculi empty into terminal bile ducts and then into progressively larger ducts, finally reaching the hepatic duct and common bile duct
In its course through the bile ducts, a second portion of liver secretion is added to the initial bile. What is contained in this secretion?
Watery solution of sodium and bicarbonate ions secreted by secretory epithelial cells that line the ductules and ducts
** This second secretion sometimes increases the total quantity of bile by as much as an additional 100 per cent. The second secretion is stimulated especially by secretin
Causes of gallstones (4)
- Too much absorption of water from bile
- Too much absorption of bile acids from bile
- Too much cholesterol in bile
- Inflammation of epithelium
Located over the entire surface of the small intestine are small pits called _____
Crypts of Lieberkühn
