Tina Hepatic/Metabolic/endocrinology: 7 Flashcards
describe a hepatic lobule
describe a portal lobule
Hepatic lobule (emphasised blood flow): polygonal histologic unit composed of numerous plates of liver cells (hepatocytes), radiating centrifugally toward a central vein. Situated around the perimeter, at each “corner” of the hepatic lobule, are branches of the hepatic artery, hepatic portal vein, and bile duct (together called the hepatic triad), and lymphatics.
Portal lobule (emphasizes exocrine function/bile flow): triangular, three central veins centered around a portal tract.
Blood flow in the liver?
70% of blood flow to the liver is _deoxygenated blood from the hepatic portal vein._5
The hepatic portal vein receives blood from the stomach, spleen, pancreas, small
intestines, cecum, and large colon.
The other 30% of blood to the liver is oxygenated, provided by the accompanying
hepatic artery.
Approximately 10% of the total blood volume at any one time is found in the liver.
Macrophages of the liver?
Kupffer cells are tissue-fixed macrophages and are estimated to make up 20% of the mass of the liver
Histology of a bile duct
The bile canaliculi are formed solely by the cell membranes of the hepatocytes. The bile ductules and ducts are lined with cuboidal and columnar epithelial cells, respectively, that make up approximately 7% of the mass of the liver.
What is hepcidin?
Hepcidin is a peptide hormone synthesized mainly in the liver.
reduces dietary iron absorption by reducing iron transport across the gut mucosa (enterocytes) and
reduces iron exit from macrophages and the liver, the main sites of iron storage.
In horses and many other species, endotoxemia and systemic inflammation therefore cause a rapid decline in serum iron.
Proteins synthetized in the liver?
synthesizes 90% of the plasma proteins, including
albumin,
many factors involved in coagulation and fibrinolysis (fibrinogen and factors II, V, VII–XIII; antithrombin III; protein C; plasminogen; plasminogen activator inhibitor; α2-antiplasmin; α2-macroglobulin; and α1-antitrypsin),
transport proteins (haptoglobin, transferrin, ceruloplasmin, hormone transport proteins), and
acute phase reactant proteins (α- and β-globulins).
The liver is the only site of synthesis of albumin, fibrinogen, and C-reactive protein and is a predominant site for production of amyloid A and hepcidin.
Urea formation and metabolism?
The liver has sole responsibility for converting free ammonia or glutamine into urea, the principal form of amino group nitrogen excretion by mammals.
Urea is formed by the irreversible condensation of two ammonia molecules with carbon dioxide. The reaction takes place in the hepatocyte mitochondria via the Krebs-Henseleit cycle.
The newly formed urea is released from the hepatocyte, secreted into the
sinusoidal blood, and transported to the kidney as blood urea nitrogen (BUN) for excretion.
Effects of glucocorticoids and insulin on the liver
glucocorticoids
indirectly influence liver gluconeogenesis by promoting
peripheral protein catabolism, thus increasing the availability
of amino acids. Insulin inhibits gluconeogenesis in
the liver
Liver and ammonia
eliminating the major toxic
byproduct of amino acid catabolism, ammonia.12,16 Tissues
and intestinal microflora generate ammonia, which is subsequently
released into the circulation.
Role of glutamate
fundamental reaction in the synthesis of nonessential amino acids is the
formation of glutamate in the liver.
glutamate is used in
- transamination reactions to form other amino acids.
- participates in the conversion of ammonia into a nontoxic(except in neuronal glial cells) transport form: glutamine.
- may be delivered to the kidney, converted back to free ammonia and excreted, or delivered to the liver for urea synthesis.
Excessive glutamine in the brain, mostly as a result of glial cell metabolism of excessive ammonia, may cause cerebral edema.
Carbohydrate metabolism
The liver is responsible for the synthesis, storage, and release of glucose.
Most soluble carbohydrates such as starches and sugars are readily broken down to glucose or other monosaccharides in the small intestine, absorbed and delivered via portal blood to the liver.
In the hepatocyte the majority of glucose is phosphorylated to glucose-6-phosphate by the enzyme hexokinase. The remaining glucose is released into the systemic circulation.
=> majority of glucose-6-phosphate is converted to glycogen for storage. A small amount of glucose-6-phosphate is oxidized to form adenosine triphosphate, although the major source of adenosine triphosphate in the liver is amino acid and fatty acid oxidation.
=> 50% of glucose enters the phosphogluconate pathway for generation of nicotinamide adenine dinucleotide phosphate, which is required as a reducing agent in the biosynthesis of fatty acids and cholesterol.
From where does the liver derive fat?
majority of short-chain fatty acids are incorporated into phospholipid or triglyceride by the intestinal epithelium and transported to the liver via the portal blood.
The remaining small percentage of fatty acids are absorbed from the gastrointestinal tract and are transported as triglyceride in chylomicrons. After formation in the intestinal epithelial cells and absorption into lymphatics, chylomicrons enter the systemic circulation via the thoracic duct and subsequently
are delivered to the liver. The liver also may take up albuminbound fatty acids released from adipose tissue.
Fat metabolism in the liver
- esterify free fatty acids into triglycerides for export to other tissues
=> triglycerides are packaged with protein, carbohydrate, and cholesterol in the endoplasmic reticulum of the hepatocyte into
very low-density lipoproteins (VLDLs), which primarily contain triglyceride, and
_high-density lipoproteins (_HDLs), which primarily contain protein and phospholipid.
=> released into systemic circulation,
=> adipose tissue takes them up or endothelial cell lipases alter their composition by removing triglyceride, forming intermediate- and low-density lipoproteins.
- liver can oxidize free fatty acids for energy to acetyl coenzyme A (acetyl CoA), a fundamental compound in the tricarboxylic acid cycle => used in the synthesis of other fatty acids, cholesterol, steroids, and ketone bodies, acetoacetate, and β-hydroxybutyrate.
- through the synthesis of acetyl CoA from glucose and most amino acids, the liver is capable of converting carbohydrates and proteins into lipids.
What does bile consist of?
Purpose and metabolism of bile acids?
Bile consists of several components, including conjugated bilirubin, bile acids, cholesterol, lecithin, water, and electrolytes
Primary bile acids are produced in the liver, mostly from cholesterol, and compose 90% of the organic portion of bile.
=> Bile acids act as detergents, facilitating the excretion of cholesterol and phospholipid from the liver into bile and facilitate the digestion and absorption of lipids and lipid-soluble compounds (vitamins A, D, E, and K) from the intestinal tract.
in the horse: cholate and chenodeoxycholate => secreted into the lumen of
the intestinal tract => may be reabsorbed or degraded by bacteria, forming the secondary bile acids, deoxycholate or lithocholate, respectively.
More than 90% of the conjugated bile acids excreted in bile and released
into the intestinal lumen are reabsorbed by the jejunum and ileum and returned to the liver via the enterohepatic circulation.
Describe the bilirubin metabolism
majority of bilirubin formed from hemoglobin and myoglobin,
Macrophages in the spleen, bone marrow, and liver (Kupffer cells) engulf the pigments first, convert it to biliverdin, and then convert biliverdin to bilirubin and release it from the cell as free, insoluble bilirubin.
= indirect-reacting or unconjugated bilirubin in the circulation
Unconjugated bilirubin is bound with albumin in the plasma to decrease its hydrophobicity and is delivered to the liver. At the surface of the hepatocyte,
the bilirubin is transferred from albumin to ligandin,
Bilirubin metabolism (once arrived in the liver)
Within the hepatocyte, the bilirubin is conjugated with glucuronide in the endoplasmic reticulum.
=> Conjugated bilirubin/ direct-reacting bilirubin excreted into the bile canaliculi. Under normal circumstances, little conjugated bilirubin escapes into the general circulation. With severe liver disease increased amounts of conjugated bilirubin
will escape into circulation and be freely filtered in the urine.
Microflora in the intestinal tract reduce conjugated bilirubin to urobilinogen and stercobilin, which impart a yellow-brown color to feces.
Urobilinogen is absorbed by the intestinal mucosa and transported back to the liver via the enterohepatic circulation.
liver extracts most of the urobilinogen; however, a small amount spills over into the urine. Urobilinogen is concentrated in the normally alkaline urine of
horses and thus is detectable.
Kupfer cells and injured red blood cells
Kupfer cells help in recycling iron from senescent or injured red blood cells, and, as a result, Kupffer cells accumulate hemosiderin and this can be pronounced even in diseasefree horses
Liver stored which vitamines and trace minderals?
storage site for several vitamins and trace minerals, including vitamins A, D, and B12; copper; zinc; and iron.
Examples for diseases resulting in
- centrilobular injury
- periportal injury
centrilobular injury: severe acute anemia, passive congestion caused by congestive heart failure (nutmeg liver), and some toxic hepatopathies (e.g., pyrrolizidine alkaloids).
Periportal (zone I acinar lobular) injury: infarction of hepatic vessels, as may occur
during verminous arteritis, or exposure to gut-derived toxins that do not require metabolism by mixed function oxidases
Common clinical signs of hepatic injury
COMMON SIGNS
- Depression
- Anorexia
- Colic
- Hepatic encephalopathy (HE)
- Weight loss
- Icterus
- Pigmenturia (yellow-brown with bilirubinuria; red-brown with hemoglobinuria)
LESS COMMON SIGNS
Photosensitization
Diarrhea
Bilateral laryngeal paralysis
Bleeding
Ascites
Dependent edema
Icterus
Icterus, or jaundice, is caused by hyperbilirubinemia with subsequent deposition of the pigment in tissues causing yellow discoloration.
increased production
of bilirubin, impaired hepatic uptake or conjugation of bilirubin,
and impaired excretion of bilirubin.
how long does bilirubin stay stable in blood tubes?
The serum bilirubin concentration is stable for several
days if the sample is protected against sunlight
Bilirubin levels in anorexia?
Complete anorexia can cause an increase in the unconjugated bilirubin concentration within 12 hours;
however, it is _unlikely to rise greater than 6 to 8 mg/d_L (102.6–136.8 μmol/L) in horses suffering purely from anorexia.
How to make the difference between hepatocellular disease and cholestasis looking at bilirubin values?
increase in the conjugated bilirubin fraction
If the conjugated bilirubin concentration < 25% of the total bilirubin value => hepatocellular disease
If the conjugated bilirubin concentration > 30% of the total value => cholestasis