Liver A&P and Functions Flashcards
Where is the liver located?
-Right upper quadrant
-Thoracic portion of the abdominal cavity
-Extends from ribs 7 to 11 along the right midaxillary line
-Largest solid organ in the body
The liver is what % of body weight?
-2.5% of body weight
-5% of a neonate’s body weight
-~1500 gms
What divides the liver into right and left?
The Falciform Ligament
What are the 4 lobes of the Liver?
-Right
-Left
-Caudate
-Quadrate
The liver is further subdivided into segments based on what?
Proximity to the hepatic and portal veins.
-8 Segments (Couinaud system)
How much CO does the liver receive?
Approx. 25% of CO via a dual arterial and venous blood supply.
-1500 mL/min
-Hepatic Artery
-Portal Vein
Nagelhout:
The hepatic artery and portal vein enter the liver and progressively branch until terminating in the hepatic sinusoids.
Describe the blood flow supplied by the Portal Vein.
-70-75% of blood flow
-50% of O2 supply
Made of the:
-Splenic vein
-Superior/Inferior Mesenteric Veins
Portal vein gets deoxygenated blood flow from the GI tract and sends it to the liver to be filtered (Hepatic 1st pass).
-Contains deoxygenated blood (85%), nutrients/toxins from GI tract, and colonic bacteria from the gut.
Describe the blood flow from the Hepatic Artery.
-20-25% of blood flow
-50% of O2 supply
Branch off of the Celiac Artery (from Abdominal Aorta)
-Provides Oxygen-rich blood
What is the pressure in the Hepatic Artery?
Whatever the arterial pressure is
What is the pressure in the Portal Vein?
-Low pressure system. Usually 6-10 mmHg.
-O2 saturation is 85%
-Low pressure here allows the liver to act as a circulatory reservoir (large venous reservoir) in case of hemorrhage.
What is the Hepatic Artery Buffer Response (HABR)?
An autoregulatory response that is inversely affected by the portal blood flow.
-Ex: Portal HTN will decrease blood supply to the Liver. In response, the Hepatic artery compensates (buffers) by picking up more blood and shunting it to the liver to make up for the lack on the portal vein side.
-A fail-safe system so that the liver actually gets perfused.
Nagelhout:
-Changes in hepatic artery or portal vein blood flow may not result in an overall change in total hepatic flow due to the hepatic artery buffer response (HABR).
-This response is a semireciprocal autoregulatory mechanism whereby changes in portal flow inversely affect hepatic arterial flow.
What is the sympathetic innervation to the Liver?
T3 - T11
What is the parasympathetic innervation to the Liver?
-Right & Left Vagus Nerve
-Right Phrenic Nerve
What ANS receptors are located on the Hepatic Artery?
Vasoconstricting Receptors:
-α1 adrenergic
Vasodilating Receptors:
-β2 adrenergic
-D1 dopaminergic
-Cholinergic receptors
What ANS receptors are located on the Portal Vein?
-α1 adrenergic
-D1 dopaminergic
What is the functional unit of the Liver?
The Hepatic Lobule.
-50,000 to 100,000 in a normal liver.
Describe the structure of a hepatic lobule.
-Hepatocytes radiate around a Central Vein in a hexagonal pattern.
-Portal Canals are in the corners, and contain lymphatic vessels, nerves, and a portal triad.
-Blood from the portal canal vessels (Hepatic Artery & Portal Vein) flows through hepatic sinusoids (where it gets cleansed via capillaries) to the Central Vein, which returns the blood to the IVC via the Hepatic Vein
-Takes 8-9 seconds for blood to flow from the portal vein to the central vein
What is the portal triad?
-Hepatic Artery
-Portal Vein
-Bile Duct
What are Cords?
Layers of hepatocytes. 1-2 cells.
-Primary function is cleansing, metabolizing, and synthesizing our blood (Hepatocytes have a large surface area that allows us to clean blood).
-Blood is released into sinusoids, where it is filtered again, before exiting into the Central Vein, and getting dumped into systemic circulation via the IVC
-Goal is to prevent toxins/bacteria from entering systemic circulation
What kind of tissue are the Capillaries in the sinusoidal space?
-Fenestrated Endothelium
-Cells have large fenestrations (holes) which permit the diffusion of fluids, large plasma proteins, and other solutes into the spaces surrounding the hepatocytes.
-Occurs via diffusion/equilibrium
What is the Space of Disse?
The space between the endothelial layer (Capillaries) and the Hepatocytes.
What is unique about the Sinusoidal Endothelial Cells?
Produce a large quantity of lymph that is nearly equal in protein concentration to plasma.
What are Kupffer Cells?
Macrophages that phagocytize 99% of the bacteria/toxins delivered from the GI tract (From PORTAL CIRCULATION) before reaching systemic circulation.
-Found in the hepatic sinusoids (Sinusoidal Space)
How does the liver function as a vascular reservoir?
-Normal blood volume of the Liver is 450 mL (10% of total blood volume
-Can hold up to 1 L of blood.
-With CHF, blood is shunted and housed in the Liver.
What are the metabolic functions of the liver? (Basic list)
Bile formation & excretion
Protein synthesis
Glycogen storage
Protein metabolism
Insulin clearance
Lactate conversion into glucose
Drug metabolism
Biotransformation
What is glycogen?
Excess glucose stored in the Liver for later use.
What is Glycogenolysis?
The process of breaking down glycogen stores in the liver (and skeletal muscle) into glucose.
-Stimulated by Epi (SNS state) or Glucagon
What is Gluconeogenesis?
The formation of glucose from non-carbohydrate molecules, Lactate and Pyruvate, or Amino Acids.
-Stimulated by a decrease in glycogen stores (Fasting state)
How does the liver affect Insulin Metabolism/Clearance?
-Pancreas secretes about 200-300 units of insulin at a time
-But, Insulin has to go through the liver first to be metabolized and filtered.
-50% of the insulin is removed during this first pass liver effect
-Protecting us from large amounts of insulin being dumped into systemic circulation
How does glucose metabolism change in the setting of Liver Dysfunction?
Patient with severe liver disease will likely have Hypoglycemia due to:
-Impaired insulin metabolism/dysfunctions in insulin clearance (not decreasing insulin release into systemic circulation)
-impaired gluconeogenesis
-impaired glycogenolysis
Most proteins are synthesized in the Liver except for _____.
Immunoglobulins
Which 2 important proteins are synthesized in the Liver?
-Albumin
-Pseudocholinesterase
What are the effects of decreased Albumin in the setting of liver dysfunction?
-Decreased plasma oncotic pressure
-Ascites (Expansion of the interstitial space and 3rd spacing)
-Increased volume of distribution
Which drug doses need to be increased due to the increased volume of distribution in liver dysfunction?
May need to increase amount of nondepolarizing muscle relaxant to achieve blockade due to increased volume of distribution (due to alterations in protein binding and body fluid shifts).
Which drugs will have exaggerated effects due to decreased protein binding?
Barbiturates
-Have an exaggerated response due to larger amounts of unbound, free drug in circulation.
A deficiency in plasma pseudocholinesterase in the setting of liver dysfunction will cause what?
Prolonged effects of succinylcholine
-And can enhance potential toxicity of ester local anesthetics
What is bilirubin a product of?
Heme metabolism.
-Classified as conjugated or unconjugated.
-Heme is converted to unconjugated bilirubin in the spleen.
Where does unconjugated bilirubin go?
Unconjugated bilirubin is NOT soluble in water, and is neurotoxic at high levels.
-Must be bound to albumin to be transported to the Liver
Once in the Liver, what happens to unconjugated bilirubin?
It is conjugated with glucoronic acid.
-It is then incorporated into bile and secreted into the intestines.
What happens to unconjugated bilirubin in the setting of liver dysfunction?
Low albumin, so nothing to transport the unconjugated bilirubin to the liver.
-Levels build up = neurotoxic
How much bile does the Liver produce per day?
1 L/day
How is bile formed?
Hepatocytes continuously secrete fluid that contains phospholipids, cholesterol, conjugated bilirubin, bile salts, and other substances (drug metabolites).
-Bile is stored and concentrated in the gallbaldder.
How is bile secreted?
In response to intestinal Cholecystokinin (CCK).
-The presence of fat & protein in the duodenum initiates contraction of the gall bladder and movement of bile via the common bile duct.
-Assists in the absorption of fat & fat soluble vitamins (A,D,E,K)
What are the bile related effects associated with liver dysfunction?
Liver disease results in impaired bile production or flow, leading to:
-Steatorrhea (fatty stools)
-Vitamin K deficiency
-Delayed removal of active drug metabolites
The Liver produces all clotting factors except for ?
Factor VIII (endothelial cells)
vWF (endothelial cells)
Calcium (diet)
Which clotting factors are Vitamin-K dependent?
2, 7, 9, 10
What happens to clotting factors in the setting of Liver dysfunction?
-Decreased clotting factors
-Only about 50% of clotting factors are needed for normal clotting. This problem can go on for awhile without being recognized.
What is the effect of abnormal bile production on clotting factors?
-Decreased fat soluble vitamin absorption (Vit K)
-So, impaired production of Vit. K clotting factors (2, 7, 9, 10)
-Higher risk of coagulation problems
What is the effect of Hepatic Obstruction on the pressure in the Portal Vein?
-Obstruction of blood flow causes Portal Hypertension (pressure of 20 mmHg)
-Back filling of blood unable to get to the liver increases pressure.
-Blood backs up into the organs, causing Splenomegaly.
How does Splenomegaly affect clotting?
Splenomegaly causes platelet sequestration and thrombocytopenia.
-Decrease in the number of circulating, functional platelets
How is Urea produced?
The liver converts Ammonia into Urea through Hepatic Deamination Processes.
-Urea is then excreted by the kidneys
What occurs with Ammonia in the setting of Liver dysfunction?
-If unable to convert Ammonia into Urea, Ammonia will accumulate
-Ammonia is neurotoxic and will lead to Hepatic Encephalopathy.
What is Biotransformation?
Exogenous drugs are deactivated in the liver and converted to products that are able to be excreted in the bile or the urine.
-Occurs via Phase 1 and Phase 2 reactions
In the setting of Liver Dysfunction, which meds will have a decreased clearance?
-Lidocaine
-Morphine
-Meperidine
-Propanolol
These drugs are highly dependent on hepatic extraction from the circulation for sufficient metabolism.
What is the role of the Liver with thyroid hormones?
-Produces T3 for thyroxine
-Produces Transferrin (brings iron to bone marrow and tissues) & Haptoglobin (binds to dead RBCs to excrete them)
-Alpha Globulins: Ceruloplasmin is produced in the Liver, and it carries copper to wherever it is needed in the body, and excess is sent to the kidneys to be excreted.
What occurs to the thyroid hormones in the presence of liver dysfunction?
-Decreased production of T3 from thyroxine
-Decreased metabolism of iron
-Decreased metabolism of copper
What is the Hepatic Enzyme System that metabolizes drugs?
CYP 450.
-Primarily responsible for Phase 1 reactions
What happens if overproduction of Hepatic Enzymes occurs in the presence of Liver Dysfunction?
-This results in tolerance to certain drugs
-Will have an increased clinical requirement for sedatives, opioids, and muscle relaxants (Roc and Vec)
What drugs induce the CYP (increase production of enzymes)?
Ethanol
Benzodiazepines
Ketamine
Barbiturates
Phenytoin
What happens if decreased CYP enzymes are produced due to Liver Dysfunction?
-Increased effect of some drugs
-Co-administration of drugs metabolized by the same CYP (Ex: Cimetidine or Chloramphenicol) will compete for binding to the enzyme’s active site.
-This results in enzyme inhibition of metabolism of one or both drugs, and leads to elevated plasma levels (increased sensitivity or toxicity)
