Hepatic PV3 part 1
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The liver can store up to _____ml of blood at any one time.
What causes the stored blood in the liver to go into the central circulation.
What are the functions of the liver?
- Filtration & Storage of Blood
- Metabolism of CHO & storage of glycogen
- Metabolism of proteins, fat, hormones, & foreign substances
- Formation of bile
- Storage of iron & vitamins
- Manufacturing of coagulation factors
TRUE or FALSE. The liver is the largest organ in the body
How much does the liver weigh? What % of body weight is it?
- 1.5kg in the adult
- 2% of body weight
Where does the liver sit?
It sits in the right and left upper quadrant of the abdomen but mostly on the right side and it’s inferior to the diaphragm.
What is the functional unit of the liver?
The lobule and each lobule has a central vein
Each lobule of the liver has a central vein, where does the blood go from this central vein?
The central vein drains into the hepatic veins and from there the blood drains into the IVC.
What extends from the central vein?
- Hepatic cellular plates extend out from the central vein.
- Each plate is 2 cells thick and then between adjacent cells within the plate are small bile canaliculi that empty into the bile ducts.
From the central plate, where does bile go?
- The bile empties into the bile ducts
- The bile then goes through the right and left hepatic ducts and these join to form the common bile duct.
- The common hepatic duct then joins w/the cystic duct to form the bile duct
- So when food arrives in the duodenum the gall bladder will send that concentrated bile through the cystic and bile ducts to the duodenum
What does the gall bladder do?
- Stores the bile
- Also functions to concentrate the bile and it does that by absorbing water and salts.
Hepatic cellular plates extend out from the central vein. What is in these plates?
- Between adjacent cells within the plate are small bile canaliculi that empty into the bile ducts
- Also in those fibers are the small portal venules.
Where does the blood supply to the portal venules come from?
this outflow from the GI tract via the portal veins.
Where does blood go from the the portal venules?
Blood then goes from the portal venules into the hepatic sinusoids lying between the hepatic plate and then from there into the central veins.
What do the venous sinusoids contain?
- Hepatic cells
- Endothelial cells
- Kupffer cells (ReticuloEndothelial cells)
What are the Kupffer cells?
large macrophages that act as phagocytes so they deal with bacteria and other foreign substances in the hepatic sinus blood.
What is the Space of Disse?
- The endothelial lining of the sinusoids have very large pores and the space beneath the lining
- Allso called the parasinusoidal space
What does the Space of Disse do?
Connect the lymphatics and since the pores are so large substances in the plasma (even plasma proteins which are pretty large and don’t usually go anywhere) move easily in the space.
What are the two surfaces of the liver?
Diaphragmatic (anterior superior and subposterior)
& visceral surfaces ((posterior/inferior)
Are the right and left lobes of the liver dependent on each other?
- Functionally independent right & left lobes
- They are approximately equal in size
How are the right and left dopes independent of each other?
Each part has its own supply from the hepatic artery and portal vein as well as its own venous and biliary drainage.
What is the Portal hepatis (AKA hepatic portal; portal fissure)??
- A transverse fissure on the visceral surface of the liver (between the caudate and quadrate lobes)
- Where the portal vein and hepatic artery enter the liver and the hepatic ducts leave.
- Gives passage to the portal vein, hepatic artery, also the hepatic nerve plexus, the hepatic ducts and lymphatics.
What is the portal triad?
- Portal vein
- Hepatic artery
- Bile passages
The liver has a high blood flow. How high is it?
- Hepatic blood flow is 100ml/min per 100g of tissue.
- Accounts for 25% of CO.
The liver gets blood from 2 places, what are they?
- Portal vein (70-75%)
- Hepatic artery (25-30%)
Describe the anatomy of the portal vein
- The portal vein is short and wide and is formed by the superior mesenteric and splenic veins posterior to the neck of the pancreas
- It then ascends anterior to the IVC and divides at the right end of the portal hepatis into the right and left branches.
What does the portal vein deliver to the liver?
- Carries poorly oxygenated but nutrient rich blood from the GI tract to the liver sinusoids.
- Also carries toxins to the liver
Why is the blood in the portal vein poorly oxygenated?
- The blood in the portal vein is partially deoxygenated in the pre-portal tissues.
- The pre-portal tissues include the stomach, the spleen, the pancreas, the small intestine and the colon.
Even though the blood from the portal vein is partially deoxygenated it still carries __-__% of the livers oxygen supply to the liver.
What kind of receptors does the portal vein have?
Alpha 1 and dopamine receptors
What is the MAP in the portal vein?
Mean pressure = 10 mmHg or less
The Hepatic artery is a branch of the celiac. It carries well oxygenated blood from the Aorta and supplies the liver with __-__% of it’s oxygen supply.
What kind of receptors does the hepatic artery have?
Alpha 1, dopamine and also beta adrenergic receptors.
Where does the blood go after it reaches the hepatic veins?
- The hepatic veins are formed by the union of the central veins of the liver.
- And these opens into the IVC just superior to the diaphragm
The portal venous system then communicates w/the systemic venous system in a # of locations. What is perhaps the most significant location??
- is the communication between the espohageal veins into either the azygous vein of the systemic system of the left gastric vein of the portal system
- When these become dilated they become esophageal varices.
What is the MAP in the hepatic artery??
Mean pressure = 90 – 100 mmHg
What is the function of the liver in regards to bile and lipids?
- Bile production & lipid absorption
- Cholesterol production
- Bile salt formation (then stored in gall bladder)
Why do we need bile salts?
The bile salts are needed for absorption of dietary cholesterol, fatty acids, fat soluble vitamins (which are A, D, E, and K)
As we know, the liver is needed for the synthesis of multiple coagulation factors
Synthesis of factors 2, 5, 7, 9, 10, 11, 12, 13, & fibrinogen
Which coagulation factors is Vit K needed for??
Vitamin K needed for formation of 2, 7, 9, 10
TRUE or FALSE. Plasma activators of fibrinolysis are cleared by the liver
Describe the importance of the liver to RBCs
RBCs release Hgb, then heme forms bilirubin which is conjugated by the liver
What does the liver store that is important for things like Hgb and myoglobin?
Liver stores excess iron needed for Hgb, myoglobin, cytochrome
Describe the livers role in CHO metabolism
- Glucose stored as glycogen
- Glycogenolysis (breaking down of glycogen into glucose)
How much glycogen is stored in the liver?
100 g glycogen stored in liver (400 g in skeletal muscle)
When is Gluconeogenesis an important liver function?
Important source of glucose after glycogen stores depleted (after 12 - 24 hours of starvation) need to create glucose from non-CHO sources
Describe the liver's role in fat metabolism
- Excess CHO & protein converted to fat
- Formation of lipoproteins (needed for fatty acid transport)
- Oxidation of fatty acids to acetoacetic acid (comes from Aceytl-Co-A which is the common intermediary of the Krebs cycle for ATP production)
Describe the livers role in protein metabolism
How many grams of Albumin does the liver synthesize per day?
10 – 15 grams/day
What % of capillary oncotic pressure is albumin?
80-90% of capillary oncotic pressure
One of the livers functions is the removal of hormones. List some hormones that are removed by the liver
- Sex hormones
An important function of the liver is the detoxification of drugs. Describe how the liver does this.
- Phase 1 and phase 2 reactions involved in drug detoxification.
- Phase 1: oxidation reduction reactions
- Phase 2: conjugation reactions.
- All managed by the cytochrome P450 system
- Whole purpose of those reactions is to create a polar water soluble substance that can’t be reabsorbed by the kidney.
- Liver also produces enzymes needed for ester hydrolysis. Drugs like: Succinylcholine and Remifentanil.
What is the % Hep A, B, C, & D incidence in the US?
- HAV – 50%
- HBV – 35%
- HCV – 15%
HDV – less than 1%
Which types of hepatitis virus may result in chronic infections?
Chronic infections may result from B, C, and D infections
Some systemic viruses can also effect the liver. Name two
The types of viral hepatitis are really indistinguishable by clinical feature or routine lab test. Some pt may be really asymptomatic or simply look like they have the flu. Others may show jaundice. Lab marker is a marked elevated aminotransferase level. How do we find out the exact type of hepatitis?
antigen/antibody testing is really needed to find out the exact virus involved.
What is the route of infection in Hep A? Does it cause serious illness?
highly contagious and d/t fecal oral contamination and poor sanitary conditions. Hep A is usually self limiting and doesn’t cause chronic hepatitis or cirrhosis.
How long are people infectious w/Hep A?
The virus is shed in the stool for days prior to symptoms and the first 1-2 weeks of a clinical illness. But by 3 weeks people are no longer infectious.
How is Hep B transmitted?
usually transmitted paraenterally or transmitted during sexual contact
What are the risk factors for Hep B?
- Risk factors: IV drug abuse, homosexual men, multiple sexual partners.
- It can also be transmitted from mother to infant.
- Because the blood products are screened they are much less likely to cause an infection from Hep B
How can you tell if someone has immunity to Hep B?
Immunity is conferred by the presence of hepatitis B surface antibodies and a large proportion of the population actually has these antibodies.
How is Hep C transmitted?
- transmitted mainly through the parenteral route also.
- 60% of cases d/t IV drug use, another 15-20% d/t sexual contact and the remainder by maternal/infant and blood products.
- Needle stick injuries are much less likely.
- Again Hep C is now screened for in blood products so that’s really the cause for post transfusion hepatitis.
What are the signficant complicaitons of Acute Hep C infections?
Chronic hepatitis, cirrhosis, & hepatocellular cancer.
What has emerged as the most dominant liver disease in the US and is the most common cause of liver transplantation?
- Hep C
- The most common cause of liver transplantation is d/t Hep C associated cirrhosis
How is Hep D transmitted?
- Unusual because it needs Hep B for replication so Hep D only occurs in patients w/Hep B.
- It is transmitted parenterally or through sexual contact. (like Hep B)
What happens if you get Hep D?
The associated hepatitis may be more severe both acutely and chronically and the cirrhosis that develops is also more severe than w/Hep B alone.
Which type of hepatitis is rarely seen in the US? How is it transmitted?
spread by the fecal oral route (like Hep A) but less contagious than Hep A and is rarely seen in the US.
What are the s/s of acute hepatitis?
- Dark urine
- Abdominal discomfort esp RUQ
- Light-colored stools
In acute hepatitis, if it is severe, we may see signs of acute liver failure like....
like acites, peripheral edema, confusion and axterixis (abnormal jerking in the hands)
What lab findings will you see in acute hepatitis?
- ↑ AST (aspartate aminotransferase)
- ↑ ALT (alanine aminotransferase)
- ↑ Bilirubin
- ↑ PT
AST and ALT are sensitive indicators of injury to hepatocytes. When does the concentration of these enzymes increase and decline?
increase 7-14 days before jaundice appears & then begin to decline shortly after the onset of jaundice.
True or False, once the patient has jaundice in acute hepatitis, the other s/s may abate?
How high does the bilirubin get in acute hepatitis?
Serum bilirubin is rarely greater than 20mg/dL. Normal is 0.3-1.9mg/dL.
When does the Alk Phos increase in acute hepatitis?
Alk phos doesn’t increase unless there’s cholestasis.
What is the usual course for acute hepatitis?
- Symptoms for 1-2 weeks before dark urine & jaundice appear
- Bilirubin ↑’s for 10 – 14 days then ↓’s over next 14 – 28 days
- AST & ALT start to ↓ just before jaundice peak
What % of patients with acute hepatitis (B and C) go on to develop chronic hepatitis
- But in about 2-7% of patients w/Hep B and 60-75% of patients w/Hep C.
- Of course chronic hepatitis (with B or C) puts the patient at risk for cirrhosis or a primary hepatocellular carcinoma but both of these could take years to develop.
What is the treatment for acute hepatitis?
Tx: symptomatic w/rest & good nutrition. If there is prolonged N/V then IV therapy may be needed and abstinence from alcohol is important. Liver transplant if permanent liver failure
How can we prevent acute hepatitis?
- Avoid exposure
When will giving immunoglobin help in acute hepatitis?
If it’s given more than 14 days after exposure it really won’t help. Hep B exposed patients may benefit from Hep B immunoglobulin if it’s given within 24hours
Patients at high risk of Hep A infections should be vaccinated. Is it active or inactive and how long does it provide protection?
Hep A vaccine is inactivated Hep A and it produces a very effective antibody response and can provide protection for 10 years or longer
How long does the Hep B vaccine last?
5 years after vaccination, 20-30% of those vaccinated will lack protection because those antibody levels decline so booster is recommended.
Descrbe the type of acute hepatitis caused by the Cytomegalovirus
- Ubiquitous herpesvirus
- Usually mild
Describe the type of acute hepatitis caused by the Epstein-Barr Virus
- Associated with infectious mono
- Mild hepatitis
Describe the drug-induced hepatitis from Tylenol
- Acetaminophen overdose is the cause of profound hepatocellular necrosis.
- Damage to liver cells is usually d/t toxic metabolites that get produced by the liver.
- Ordinarily these metabolites would get conjugated with glutathione but when the dose of acetaminophen is too high the liver stores of glutathione are depleted and so what happens is those toxic metabolites accumulate and destroy the liver cells
What can we give to prevent the hepatotoxicity associated with Tylenol overdose?
There is a drug called anlcetylcystine if it’s given within 8hr of overdose of acetaminophen there is dramatic decreased risk of hepatotoxicity.
Sometimes hepatitis can occur from even normal doses of Tylenol. Why??
If the usual levels of glutathione are decreased (fasting or long term alcohol use) hepatotoxicity can occur from even normal doses of acetaminophen.
What is Halothane hepatitis
- an immune mediated situation where certain IgG antibodies are present.
- The antibodies in this case are microsomal proteins on the surface of the liver cells and these proteins on the surface of the liver cells have been modified by a metabolite of Halothane forming a neoantigen.
If thethe metabolites causing Halothane Hepatitis are also formed by Isoflurane and Desflurane, why don't we see it as much w/those volatiles?
so there can be a cross sensitivity but the reason we don’t see “halothane hepatitis” w/Isoflurane and Desflurane is that neither of those are metabolized to the same degree as Halothane. But if there is a genetically susceptible person there could be a cross sensitivity reaction.
What is the Bilirubin, AST & ALT, Alk. Phose, & Causes of Pre-hepatic dysfunction
- Bilrubin:↑ unconjugated
- AST & ALT: normal
- Alk. Phos. : normal
- Causes: hemolysis, hematoma resportion, & bilirubin overload
What is the Bilirubin, AST & ALT, Alk. Phose, & Causes of Intra-hepatic (hepatocellular) dysfunction
- Bilrubin:↑ unconjugated
- AST & ALT: markedly ↑
- Alk. Phos. : normal - slightly↑
- Causes: Viral, Drugs, Sepsis, Hypoxemia, & Cirrhosis
What is the Bilirubin, AST & ALT, Alk. Phose, & Causes of Post-hepatic (Cholestatic) dysfunction
- Bilrubin:↑ conjugated
- AST & ALT: normal -slihglty ↑
- Alk. Phos. : markedly↑
- Causes: Biliary tract stones & Sepsis
What is the normal ALT and AST and Alk Phos?
- ALT: 10-35 U/L.
- AST: 0-35.
- Alk. Phos: 42-136.
What is the normal Bilirubin? (direct, indirect and total)
- indirect/unconguated: 0.1-1mg/dL
- direct/conguated: 0.1-0.3mg/dL
- total: 0.1-1.2mg/dL
What is the normal albumin?
Normal albumin is 3.5-5g/dL
Does overall hepatic function has the better prognostic indicator of AST and ALT???
- Elevated bilirubin and PT are better prognostic indicators of overall hepatic function then either the ALT or AST.
- Because in general severe liver disease is needed for those to be elevated.
What are the s/s of chronic hepatitis?
- Similar to acute
- Range on a continuum
What lab values do you see w/chronic hepatitis?
- ↑ AST & ALT
- Bilirubin (Normal in chronic viral & ↑ in autoimmune)
- ↓ Albumin
- ↑ PT
When is chronic hepatitis usually defined?
represents long term elevation in LFTs w/inflammation seen on liver biopsy. Usually defined as when hepatitis has lasted for 6 months or longer
List as many causes for chronic hepatitis as you can think of
- Autoimmune hepatitis
- HBV & HCV
- Wilson’s disease
- α 1 anti-trypsin deficiency
- Primary biliary cirrhosis
- Primary schlerosing cholangitis
What is Wilson's disease?
inherited disorder where there is too much copper in the body and then the copper will damage the liver along w/other organ systems.
Chronic hep B infection is present in about ___% of the worlds population. And about ____percent of those in the US are carriers of the antigen
For Hep B, Age at the time of the diagnosis is a significant determinant of the chronicity. __% of infected neonates become carriers
Who is more likely to be a carrier for Hep B, men or women?
What is the treatment for Hep B aimed at?
- aimed at suppressing Hep B replication.
- Drugs are some of the antiretroviral
What happens if a patient w/Hep B receives a liver transplant, can we stop the antiretrovirals?
- No, If liver transplant is performed, Hep B will infect the transplanted liver in nearly all recipients.
- So post transplant those antiretrovirals need to be continued along w/Hep B immunoglobulin.
- Together those can decrease the rate of reinfection to about 10%.
Chronic hepatitis follows acute infection of Hep C in up to __% of patients. An estimated ___% of the US population are carriers of Hep C
How do we diagnose chronic hepatitis from Hep C?
Dx is based on lab data with persistent increase aminotransferase enzyme levels as well as antibodies to Hep C
When does a person w/Hep C develop cirrhosis and liver cancer?
The patient hx of these can cover 10 or more years with cirrhosis or liver cancer developing after 10-20 years.
When would we see a more rapid rate of progression of Hep C?
A more rapid rate progression to cirrhosis is more likely in the male patient over age 40 at the time of initial infection. Particularly if he consumes a significant amount of alcohol daily and has a coinfection with other liver viruses or w/HIV.
What kind of treatment is indicated in Hep C?
- Interferon can be helpful in normalizing the aminotransferase enzymes and decreasing inflammation in about 40% of the patients but the response from a single drug therapy isn’t really sustained.
- Combining interferon w/antiviral drugs will increase the % of patients having a sustained response.
What is the most common indication for liver transplantation???
- Chronic hep C with liver failure is the most common indication for liver transplant.
- Although the virus will infect the transplanted liver, the illness that results is usually mild and rarely progresses to liver failure.
Drug-induced chronic hepatitis can be seen with.....
methyldopa, trazadone, isoniazids (anti-TB), as well as the sulfonamides, acetominophen, ASA,
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