Hepatic Physiology Flashcards
Ascites
Fluid accumulation in peritoneal cavity
- liver dysfunction is the major cause
Icterus
Elevated bilirubin levels
- aka: hyperbilirubinemia, jaundice
Cirrhosis
Condition in which normal cells are replaced by scar tissue
- end stage occurrence
Portal hypertension
Hypertension in the portal vein and its branches
- elevated bp in the portal vein or elevation in interstitial hydrostatic pressure
Metabolism
Sum of all anabolic and catabolic reactions as it relates to use of all nutrients
Liver functions
- filtering and storage of blood (largest cardiac output)
- metabolism of carbs, proteins, fats
- metabolism of hormones, drugs, toxins
- formation of cholesterol and bile (fat synthesis)
- storage of vitamins and iron
- production of coagulation factors
- production of plasma proteins
- lymph formation
The liver makes every ____ in the body
Protein
_____ is relevant during ascities
Lymph formation
- excess lymph gets into the peritoneal cavity
Liver lobule
Basic functional unit of liver
Hepatocytes
Main liver cells
- produce bile, which is drained into bile canaliculi
Sinusoids
Protein, lymph production
- holes in between endothelial cells leak into lymphatics
Portal vein
Main blood supply to the liver
Hepatic artery
2nd main blood supply
- filters bacteria coming from portal vein (hepatocytes)
Kupffer cell
Macrophages, makes sure bacteria does not go into systemic circulation
Liver structure
Largest internal organ
- 2-5% total body weight
- receives 30% of cardiac output
Liver lobes
6 lobes
- right and left medial
- right and left lateral
- quadrate
- caudate
Venous sinusoids
Lined by endothelial cells with large pores to allow movement of plasma proteins
- contains Kupffer cells that keep less than 1% of GI bacteria from entering systemic circulation (defense mechanism)
Lymph formation
50% of lymph is formed in the liver
- sinusoidal endothelial cell leak fluid/proteins into “space of Disse”
- lymph from liver has protein conc of 6 g/dl
Lymph flow
Lymph –> space of Disse –> lymph vessels –> lymphatic system
Increased sinusoidal pressure increases lymph production
Any disease of liver, especially chronic diseases
- fibrosis, cirrhosis
- once pressure rises enough, the liver sweats lymph (ascities)
- liver lymph volume can increase by 1 liter or more
Extramedullary hematopoiesis
Production of blood cells outside of bone marrow during times of need
- cytokine stimulation
- hypoxia
Liver blood flow breakdown
- 20% from hepatic artery
- 80% from portal vein
Liver oxygen supply breakdown
- 50% from hepatic artery
- 50% from portal vein
Portosystemic shunts
Shunting of blood from portal circulation to systemic circulation without passing through the liver
- congenital
- acquired
Congenital shunts
Intrahepatic or extrahepatic vessel that does not allow blood to take a normal course thru the liver
- ex: portocaval shunt where portal vein empties directly into caudal vena cava
Consequences of congenital shunts
- impaired liver development = stunted growth
- liver dysfunction = build up of toxins (ammonia), poor ability to metabolize anesthetics
- liver failure
- end stage cirrhosis without repair
Portal pressures
- pressure in portal vein: 9 mmHg
- pressure in hepatic vein leading to vena cava: 0 mmHg
- low pressure gradient gets blood from intestines and spleen, thru liver, into vena cava and back to right atrium
Ascites
Sweating from surface of the liver due to increased hydrostatic pressure in hepatic veins
- fluid similar to plasma in regards to protein content
OR: due to increased hydrostatic pressure in vena cava
- increases lymph flow
Causes of portal hypertension
- cirrhosis
- severe infection
- chronic biliary tract obstructions
- portal vein thrombosis (increase hydrostatic pressure)
Consequences of portal hypertension
- GI edema/ulceration
- severe GI signs and protein loss
- ascites
- acquired portosystemic shunts
Acquired shunts
Multiple tortuous vessels outside of the liver develop due to high pressure in the liver (portal hypertension)
- acts as a relief valve for portal vasculature
- located all throughout the abdomen (often near the kidney)
- worsens liver function
Causes of congestion
Right sided congestive heart failure
- HW disease
- congenital disease
- cor pulmonale
Consequences of congestion
- GI edema/ulceration
- severe GI signs and protein loss
- ascites
Obstruction of lymph flow/congestion is due to ____
Right sided heart failure
Portal hypertension is due to ___
Increased resistance to blood flow thru the liver
Increased sinusoidal pressure in the liver is caused by ______
Anything that makes the liver sick enough
Hypoalbuminemia
<1.6 mg/dl = potential for effusion
- pure transudate (water like)
What is the main production site for albumin?
Liver!!
Can the liver repair itself?
Yes!
- insult>repair
- transforming growth factor B –> cytokine secreted by hepatocytes, stops liver cell proliferation
Instances where the liver is unable to repair itself
Injury > fibrosis > cirrhosis
Vitamins stored in the liver
A, D, B12
Iron
Stored as ferritin in hepatic cells by combining with apoferritin
- released from storage in times of need
Role in coagulation
Makes most of proteins needed in this process
- fibrinogen
- prothrombin
- clotting factors: 2, 7, 9, 10 are vitamin K dependent
Role in drug/hormone/toxin metabolism
- detoxify antibiotics
- excrete antibiotics into bile
- chemical alteration of hormones
- excrete hormones
- calcium excretion
Bilirubin
Green/yellow pigment that is the major end product of hemoglobin degradation
- comes from old/sick RBCs that get phagocytosed by macrophages
Hemoglobin is split into _____ and ______
Globin and heme
- releases free iron and a substrate from which bilirubin is formed
- biliverdin –> free bilirubin (unconjugated) is released from macrophages into circulation
It what form is bilirubin transported throughout the body?
Unconjugated bilirubin joins with albumin
- reaches the liver and is absorbed through hepatocyte membrane
Conjugated bilirubin
Conjugation with glucuronide, sulfate, etc occurs in the hepatocyte
- excreted into bile canaliculi and then into intestines
Fate of bilirubin
Converted via bacteria to urobilinogen
- urobilinogen is reabsorbed thru intestinal mucosa back into blood —> mostly goes back to liver for re-excretion into gut and is oxidized to stercobilin (feces)
- remaining 5% is excreted by kidneys and oxidized to urobilin (urine)
Increased bilirubin
Aka: hyperbilirubinemia, icterus, or jaundice
- yellow tint to body tissues due to excessive build-up of conjugated or unconjugated bilirubin
- normal range is 0.2-0.6 mg/dl
- jaundice is noted at a bilirubin around 2 mg/dl
Hyperbilirubinemia causes
- hemolytic anemia (prehepatic)
- liver failure/dysfunction
- obstruction of biliary tracts in the liver
- obstruction of posthepatic biliary system (gallbaldder, common bile duct, pancreas, etc)
Hepatic metabolism
- high rate of metabolism
- shares substrates with other organs
- processing and transportation to other organs
Carbohydrate metabolism
- storage of glycogen
- conversion of galactose and fructose to glucose
- gluconeogenesis
- formation of other compounds from “byproducts” of CHO metabolism
Glycogen storage
Allows removal of excess glucose in blood
- released in times of need (stress, hypoglycemia)
Gluconeogenesis
Maintains normal blood glucose between meals
- uses amino acid from protein and glycerol from triglycerides to make glucose
Lipid metabolism
Oxidation of fatty acids to supply energy for body functions
- synthesis of cholesterol, phospholipids, and most lipoproteins
- synthesis of fat from proteins and carbs
______ of cholesterol made in the liver is converted to bile salts
80%
- remainder is transported in lipoproteins in the blood to needy tissues
- cell membrane formation
- intracellular structure formation/reactions
Phospholipids are transported by ______
Lipoproteins
- cell membrane function
- intracellular structure formation/reactions
- second messenger systems
Lipid metabolism process
Neutral fat –> glycerol + FA –> beta oxidation –> acetyl CoA
Where does acetyl CoA go?
Citric acid cycle
Leftover CoA —> acetoacetic acid –> transported in circulation to other tissues –> conversion back to acetyl CoA for oxidation and energy production by needy tissue
Protein metabolism
- breakdown of amino acids for energy, conversion to CHO and fat
- formation of urea for removal of ammonia from body fluids
- formation of all plasma protiens
- manipulation of amino acids and synthesis of other stuff from amino acids (non-essential FA formation)
Manifestations of liver disease
- decreased albumin –> decreased colloidal osmotic pressure = effusion and edema
- decreased glucose
- increased bilirubin
Hepatic encephalopathy
Occurs due to accumulation of ammonia and hormones
= seizures, dullness, lethargy, etc
- worsened after a meal
Coagulopathies
- increased prothrombin time
- increased partial thromboplastin time
- platelet dysfunction
- decreased fibrinolysis
- excessive fibrinolysis
Alanine aminotransferase
ALT
- most common/important
- leakage enzyme made inside hepatocyte
- indicators of hepatic injury (biomarkers of necrosis)
Aspartate aminotransferase
AST
- leakage enzyme made inside hepatocyte mitochondria
- indicators of hepatic injury (biomarker of necrosis)
- more of a muscle enzyme
Alkaline phosphatase
ALP
- induced enzyme made in lining of bile canaliculi
- elevated with cholestasis
Gamma glutamyl transpeptidase
GGT
- excellent marker for hepatobiliary disease especially biliary tract disease
What to look for on bloodwork
- increased bilirubin
- decreased albumin
- decreased cholesterol
- decreased glucose
- decreased BUN
= increased ALT/AST and ALP/GGT
Bile acid assay process
- baseline BA
- feed small meal with protein/carb
- 2 hr post meal BA
Bile acid assay results
If 2 hr post meal is elevated = liver failure or PSS
- pro: can do in practice
- cons: have to feed patient, cannot rely on results if bilirubin is elevated, determine if hepatic or post-hepatic
Ammonia tolerance test process
- baseline ammonia
- give 100 mg/kg ammonia
- 30 minute post ammonia
Ammonia tolerance results
If baseline, or post ammonia is elevated = liver failure or PSS
- pro: can do if bilirubin is elevated
- con: not able to do in practice, can cause hepatic encephalopathy/coma
