GI E2- Diseases of the Liver Pt 1

What is the functional unit of the liver that consists plates of hepatocytes hexagonally arranged around a central vein?

Lobule

What are wide, leaky capillaries without a basement membrane that empty into the central vein?

Sinusoids

What is the breakdown of heme metabolism?

Bilirubin

What does jaundice result from?

Hyperbilirubinemia

Which type of bilirubin is water soluble?

Direct (conjugated)

Which type of bilirubin is lipid soluble (90% of the serum bilirubin in healthy adults)?

Indirect (unconjugated)

What facilitates digestion, emulsification, absorption of fat via micelles, and solubilizes cholesterol?

Bile

Describe the pathway of bile secretion

Hepatocytes produce bile → bile duct → R or L hepatic duct → common hepatic duct (joins cystic duct of GB) → common bile duct (joins pancreatic duct) → hepatopancreatic ampulla (ampulla of Vater)

What controls bile secretion?

Parasympathetic stimulation via vagus nerve & hormonal stimulation (CCK causes GB to empty, Secretin causes bile secretion)

What functions in the synthesis of serum proteins, hormonal and growth factors, regulates nutrients, produces bile & carriers, conjugates bilirubin, and detoxes drugs for excretion?

Hepatocytes

Hepatocellular or cholestatic disease?

• increased AST, ALT predominately

Hepatocellular disease

Hepatocellular or cholestatic disease?

• retention of bile in the liver

• increased ALP

Cholestatic disease

The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratio can be a useful marker for what specific diseases?

Liver diseases

Which of the following conditions is most likely?

• AST- 160

• ALT - 80

Alcoholic hepatitis

Which of the following conditions is most likely?

• AST- 46

• ALT- 78

Chronic hepatitis C

Which of the following conditions is most likely?

• AST- 400

• ALT- 800

Acute viral hepatitis

Which of the following conditions is most likely?

• AST- > 1, 000

• ALT- > 1,000

Acute Tylenol toxicity & ischemic hepatitis

What causes LFT elevations?

Toxins (new meds, Tylenol), viral, ischemia, passage of a gall stone

What is the gold standard to stage fibrosis?

Liver biopsy

What are disadvantages to liver biopsies?

Invasive, expensive, risk pain & bleeding

sample is small & sampling error can occur

What newer test is non invasive and measures the velocity of sound waves passing through the liver and gives a score that is converted into a liver stiffness measurement?

Fibroscan (liver ultrasonographic elastography)

What is a harmless, hereditary condition where the conjugation of bilirubin by glucuronide is impaired?

Gilbert’s syndrome

What causes the impairment of bilirubin conjugation by glucuronide seen in Gilbert’s syndrome?

Mild decrease in uridine phosphate (UDP) or glucuronyl transferase

** all other causes have been eliminated

What condition?

• mildly persistently elevated unconjugated bilirubin

  • occurs w/ illness (flu), fasting, & some drugs

• Asx & often found incidentally

• Harmless & no treatment required

Gilbert’s syndrome

What is the loss of hepatocellular function or interrupted blood flow through?

Hepatocellular failure

Due to the livers large reserve capacity, significant injury can be masked in hepatocellular failure. How much of the liver must be destroyed before life is threatened?

80%

What are ssx of hepatocellular failure?

Jaundice, muscle wasting, ascites, excessive bleeding, vitamin or blood protein deficiencies, glucose imbalance, impaired hormone production

The following pathophysiology is seen in what condition?

• Dec protein → dec production of clotting factors & hypoalbuminemia → generalized edema

• Abnormal release/storage of glycogen → hyper/hypoglycemia

• Dec bile salt production → impaired vitamin (ADEK) absorption

• Dec lipoprotein processing → dyslipidemia

• impaired processing or metabolism of:

  • endogenous steroid hormones

  • by products of protein metabolism (ammonia → urea)

  • drugs/toxins

  • bilirubin → jaundice

Hepatocellular failure

Due to the impaired processing of endogenous steroid hormones in hepatocellular failure (estrogen), what signs can be seen in men?

Gynecomastia, impotence, testicular atrophy

Due to the impaired processing of endogenous steroid hormones in hepatocellular failure, what signs can be seen in women?

Irregular menses, palmar erythema, spider telangiectasia

What is the yellowish coloration of sclera, skin, and mucous membranes due to hyperbilirubinemia (either conjugated or uncojugated bili accumulates)?

Jaundice

What category of jaundice?

• due to increased bilirubin production

• ex: hemolytic disease

Prehepatic

What category of jaundice?

• deficient bile production or bilirubin metabolism due to liver disease

• ex: hepatitis

Hepatic

What category of jaundice?

• due to bile drainage blockage

• ex: gallstones or pancreatic/bowel cancer

Posthepatic

What is the AC, 9H mnemonic for complications of liver failure?

Ascites, Coagulopathy

Hypoalbuminemia, portal HTN, Hyperammonemia, Hepatic encephalopathy, Hepatorenal syndrome, Hypoglycemia, Hyperbilirubinema (jaundice), Hyperestrinism, HCC

What is the irreversible end stage of hepatic injury characterized by diffuse hepatic fibrosis → permanent changes in hepatic blood flow/liver function?

Cirrhosis

What can cause cirrhosis?

Alc liver dz, chronic hepatitis, toxin induced, autoimmune hepatitis, primary biliary sclerosis, non-alc fatty liver dz

What are the ensuing events of cirrhosis?

Portal HTN & impaired biochemical functions → dec albumin & clotting factor synthesis

What assesses the functional hepatic reserve of cirrhosis by measuring the disease severity and is also a predictor of morbidity and mortality?

Child-pugh classification

What assesses the functional hepatic reserve of cirrhosis by using bilirubin, creatinine & INR and also helps determine transplant status?

Model for end stage liver disease (MELD)

What condition?

• Pts w/ liver failure experience occasional kidney failure- rising serum cr & oliguria

• Kidney is fine but intrarenal blood flow is disturbed d/t imbalance bt vasoconstrictive & vasodilation mechanisms of liver dz

• usually acute and progressive but can be chronic (poor prognosis)

Hepatorenal syndrome

What is the treatment for hepatorenal syndrome?

Preventative, supportive, hemodialysis, liver transplant if done early enough, r/o any reversible cause of renal failure

What condition is a chronic obstruction in blood flow through the liver & venous drainage is congested?

Portal HTN

What kind of blood supply does the liver have?

Dual - hepatic artery (20%) and portal vein (80%)

What does the congestion of venous drainage in portal HTN cause?

Abnormal venous patterns → varices, caput medusae, ascites

What is the superficial enlargement of umbilical veins and is pathognomonic for portal HTN?

Caput medusae

What is the accumulation of peritoneal fluid?

Ascites

Why do esophageal varices occur in portal HTN?

Collateral venous pathways (varices) dilate from inc portal vein pressure in an attempt to transport blood from the splanchnic bed around the cirrhotic liver to the heart

What can cause portal HTN?

Alcoholic cirrhosis, post hepatic cirrhosis, chronic infx

The following symptoms are seen with what condition?

• Muscle wasting

• spider angiomata

• jaundice

• caput medusae

• splenomegaly

• inc liver failure- ascites (transudate), AMS

Portal HTN

What is the pathologic accumulation of fluid w/in the peritoneal cavity (intra-abdominal collection of fluid) caused by decreased oncotic pressure?

Ascites

What is the treatment for ascites?

Abdominal paracentesis (analyze fluid, SAAG)

Na restriction 800 mg/day, fluid restriction 1 L/day

Diuretics: spironolactone, + loop (Lasix) to delay action

Tx fail/refractory: albumin infusion, abd shunts (peritovenous), TIPS

What is a complex neuropsychiatric syndrome that has distinctive EEG changes and symptoms ranging from mild confusion to lethargy, stupor and coma?

Hepatic encephalopathy

What ssx are associated with hepatic encephalopathy?

Reverse sleep cycle, dementia, psychotic sx, spastic myelopathy, asterixis “liver flap” (classic finding)

What is hepatic encephalopathy associated with?

Fulminant hepatic failure (onset w/in 8 wks of liver injury w coagulopathy) & severe chronic liver disease

What is the main cause of symptoms of hepatic encephalopathy and correlated with the severity of dysfunction?

Increased arterial ammonia level

What is the treatment for hepatic encephalopathy?

Correct cause, recommend AGAINST protein restriction, inc excretion of nitrogenous wastes

Osmotic diuresis or abx: lactulose, amoxicillin & rifampin, spironolactone

What often develops with grade 3 or 4 hepatic encephalopathy?

Cerebral edema → inc ICP → dec perfusion of brain → cerebral hypoxia (major cause of death)

What sx are associated with cerebral edema?

Deepening coma, systolic HTN, decerebrate posture, pupillary dilation, resp arrest w brain herniation

What is the treatment for cerebral edema?

1st line: IV mannitol infusion (pt in semi-fowler position)

2nd line: sodium pentothal

Other: moderate hypothermia

How does IV mannitol infusion work for cerebral edema?

Decreases edema via osmotic pull of water form brain while patient in semi fowler position

What is inflammation and necrosis of the liver cells resulting from different types of injury?

Hepatitis

What is the etiology of hepatitis?

Viral, alcoholic, drug induced, autoimmune, hereditary disease

What are 90% of cases of acute hepatitis?

Acute viral hepatitis (A, B, C, D, E)

What causes chronic viral hepatitis?

Hep B & C

Which type of viral hepatitis?

• continued disease activity > 6 mos

• inflammation is confined to portal triad w/o destruction of normal liver tissue

• inc serum transaminases

Chronic viral hepatitis

Destruction of normal liver tissue occurs most frequently in what type of hepatitis?

Acute hep C

What condition has the following presentation?

• prodrome of viral like sx

  • anorexia, N, V, malaise, aversion to smoking

• low grade fever

• hepatomegaly

• ± jaundice

• normal-low WBC

• marked transaminase elevations early in course

Hepatitis

The following symptoms are associated with what phase of acute viral hepatitis?

• low grade fever

• N, V, anorexia

• RUQ or epigastric pain

• Malaise, myalgia, arthralgia, fatigue

• aversion to smoking

Prodromal phase

The following symptoms are associated with what phase of acute viral hepatitis?

• jaundice in some

• icteris of sclera

• worsening of prodromal sx

Icteric phase

The following symptoms are associated with what phase of acute viral hepatitis?

• increasing sense of well being

• return of appetite

• resolution of jaundice, abd pain, & fatigue

Convalescent phase

Describe the course of acute viral hepatitis

Acute illness lasts 2-3 wks (hep A complete recovery in 9 wks, hep B complete recovery in 16 wks)

Which hepatitis are more likely to be chronic?

B, C, and D

What can result in severe cases of acute viral hepatitis?

Liver failure & its complications (hepatic encephalopathy, hepatorenal syndrome, bleeding diathesis), fulminant hepatitis

Which type of hepatitis?

• acute short lived illness with very low mortality and no long term sequala

• fecal oral transmission - contaminated food/water

• sx: malaise, anorexia, N, low grade fever, RUQ pain, jaundice ~ 2 wks

• generally self limited lasting ~9 wks

Hepatitis A

In hepatitis A, when does virus excretion start and when does it clear from feces?

Starts 2 weeks before clinical illness & clears from feces after the first week of physical sx

When are blood and stools most infectious in hepatitis A?

During incubation period (2-7 weeks) & early illness

What is the diagnosis for hepatitis A?

Anti-HAV IgG (previous infx & immunity) & anti-HAV IgM (acute infx)

Which indicates a previous hep A infection and immunity?

Anti-HAV IgG

What is the treatment for hepatitis A?

Rest, nutritious diet, avoid hepatotoxins (alc, Tylenol), separate and clean items/laundry, active immunization (2 wks before travel, exposure, etc)

Which type of hepatitis?

• longer and more insidious onset; slower recovery

• can survive for atleast 7 days

• longer course of dz → inc risk of HCC

• transmission- parenteral, sexual contact, perinatal

• present in- blood, saliva, semen, vaginal secretions

Hepatitis B

What route of of HBV transmission is associated with 90% risk of chronic infection?

Mother to neonate

What are RF for HBV?

Working in health care, transfusions, dialysis, acupuncture, tattooing, extended overseas travel to endemic area, residence in institution/correctional facility

What type of hepatitis?

• insidious onset- can easily be missed

• incubation 2-6 mos

• sx: fever, fatigue, loss of appetite, N, V, abd pain, dark urine, clay colored BMs, arthralgia, pruritus jaundice

HBV

Who does the CDC recommend HBV testing for?

Anyone born between 1945-1965**, pts on immunosuppressive therapy

and a lot more like 2 slides on it idk just read it

What is the dx for HBV?

Hepatitis panel, LFTs, U/S guided laporoscopic bx

What 3 distinct antigen-antibody systems are useful markers for HBV diagnosis?

HBs, HBc, HBe

What indicates an acute HBV infection?

HBsAg

What indicates immunized or recovered from HBV?

Anti-HBs

What appears shortly after HBsAg is detected & fills the serological gap in pts who have cleared HBsAg and have not yet made anti-HBs?

IgM anti-HBc

What appears during acute hepatitis but persists indefinitely, no matter if pt recovers or becomes chronic?

IgG anti-HBc

What appears during the incubation period of HBV shortly after detection of HBsAg & indicates viral replication and infectivity?

HBeAg

What is there an increased risk of with chronic HBV cases?

Cirrhosis or HCC (esp in endemic areas, seen at younger age)

*prevent HCC w/ HBV vaccine

What is the treatment for acute cases of HBV?

Supportive, usually resolves spontaneously

What is the treatment for HBV fulminant disease?

Aggressive tx for coagulopathy, encephalopathy, cerebral edema, etc

What is the treatment for chronic HBV?

Antivirals → Tenofovir, Entecavir, Lamuvidine (has inc resistance)

What are recommendations for HBsAg positive patients?

Vaccinate sexual contacts, use barrier protection, dont share toothbrushes/razors, cover wounds, clean blood spills w/ detergent or bleach, don’t donate organs/blood/sperm

T/F: Pts who are HBsAg positive should -

• should not participate in activities, including contact sports

• be excluded from daycare or school participation and be isolated from other kdis

• should not share food, utensils, kiss others

False

When should people receive HBV recombinant vaccine?

3 doses at birth, 1 and 6 mos, may need booster after 10 yrs (check titer)

What should HBV patients receive to decrease the risk for fulminant hepatitis with a superimposed hepatitis infection?

Hep A vaccine