The Liver Flashcards
What are the basic functions of the liver?
Functions of the Liver
- It is the body’s main factory responsible for the synthesis and storage of amino acids, proteins (enzymes, clotting factors, etc.), vitamins, fats (including lipids and cholesterol)
- Responsible for detoxification of materials in our diet, including drugs and alcohol
- Produces bile, which not only helps digest fat, but is also a way of eliminiating waste materials (ex. bilirubin and drugs)
- It is essential in blood glucose homeostasis, including the storage of glycogen
- It is also a very important part of our innate immune system (Kupffer cells = macrophages of the liver)
Describe the metabolism of bilirubin.
Bilirubin metabolism
- Hb is broken down to heme and globin
- Heme metabolized to biliverdin and then to unconjugated bilirubin
- Unconjugated bili is transported to liver on albumin
- In the hepatocytes, bili is conjugated by UGT enzyme (making bili more water soluble)
- Conjugated bili flows down bile duct and enters duodenum
- Bacteria in colon act upon bili to form stercobilin (makes stool brown color) and urobilinogen (makes urine yellow color)
- Blockage to bile flow (ex. common bile duct stone or cancer in head of pancreas), the bile duct becomes dilated (U/S):
- Stool turns clay-coloured
- High conjugated bili = jaundice and dark tea coloured urine
- Pruritus and ALP increases
What is cholestasis?
Cholestasis = lack of bile flow
- Can occur at the level of the canaliculus or intrahepatic bile ducts (intrahepatic cholestsasis, where U/S shows no dilated ducts) or in extrahepatic bile ducts (where U/S shows dilated bile ducts)
What is the natural history of liver disease?
How do pts with liver disease present?
List the stigmata of chronic liver disease.
Stigmata of Chronic Liver Disease
- Clubbing = dilation of finger tips and loss of nail bed angle, may be seen in PBC or if hypoxic from hepatopulmonary syndrome
- Palmar erythema = redness of thenar and hypothenar eminence of palms
- Terry’s nails = increased size of white “moon” of the nail due to low albumin
- Dupuytren’s contracture = thickening of the sheath surrounding the finger flexor tendons
- Spider nevi = telangiectasia on the skin which fill from the centre
- Gynecomastia = enlargement of the breast tissue
- Altered hair distribution
- Caput medusa = enlargement of the superficial vessels in the skin of the abdominal wall around the umbilicus
- Hepatosplenomegaly
- Ascites
- Testicular atrophy
- Bruising = decreased production of clotting factors or low platelets
- Edema = swelling in tissues
Which stigmata of chronic liver disease are due to a high estrogen state?
- Palmar erythema
- Spider nevi
- Gynecomastia
- Altered hair distribution
- Testicular atrophy
What is Murphy’s sign?
Murphy’s sign
- Sign of acute cholyecystitis
- Pt will suddenly stop inspiration when the inflamed gallbladder touches the palpating hand
What testing would you complete for viral causes of elevated hepatocellular enzymes?
- Viral serology
- PCR
What test would you order if suspicious of Hereditary Hemochromatosis?
HH = Transferrin Sat >45%
What testing would you order if suspicious of Wilson’s diseease?
Wilson’s disesae = Decreased ceruloplasmin
- 24 hr urine copper study
If a patient has a decrease in alpha-1-antitrypsin wat confirmatory testing would you complete?
Phenotyping
If suspicious of Autoimmune hepatitis (AIH) what testing would you complete?
AIH
- Positive ANA +/- ASMA
- Increased IgG
- Liver biopsy
What testing do you complete if suspicious of Primary Biliary Cirrhosis (PBC)?
PBC
- AMA
- Increased IgM
What testing would you complete if suspicious of a pt with NAFLD?
NAFLD
- Glucose fasting
- Fasting lipid profile: cholesterol, triglycerides, LDL, HDL
What are the risk factors for presentation of gall stones (The 7 Fs)?
The 7 Fs
- Female = more common in women
- Fertile = 30% of pregos get sludge and 1-3% stones
- Fifty = 25% of women over 50
- Family = American Indians > Hispanics >> Caucasians
- Fat = 1/3 of obese (BMI >30)
- Fasting = rapid wt loss can result in stones
- Farmacology = ceftriaxone, octreotide
Describe the biliary colic presentation of gall stones. What is the management?
Biliary Colic - gallstone transiently impacted in cystic duct, no infection
Presentation: steady RUQ pain that comes on slowly and lasts 3-4 hrs
- Crescendo-decrescendo pattern
- May present with chest pain
- N/V
- Frequenty occurs at night or after fatty meal, not after fasting
- Patients often restless
- No peritoneal findings, no systemic signs
Diagnosis: U/S shows cholelithiasis, may show stone in cystic duct
Management: laprascopic cholecystectomy
Describe the presentation of acute cholecystitis. What is the management?
Acute Cholecystitis - inflammation of the gallbladder due to sustained gallstone impaction of cystic duct
Presentation: fever, RUQ pain, Murphy’s sign on PE or U/S, high WBC
- Boas’ sign = right subscapular pain
Management: Antibiotics and cholecystectomy
What is choledocholithiasis? What are the clinical features and treatment?
Choledocholithiasis - stones in CBD
Presentation: 50% asymptomatic, often have history of biliary colic, tenderness in RUQ or epigastrium, alcoholic stool, dark urine, fluctuating jaundice
Treatment: If no evidence of cholangitis treat with ERCP for CBD stone extraction possibly followed by elective cholecystectomy in 25% of pts.
What is the presentation of acute cholangitis and what is the management for these pts?
Acute Cholangitis - obstruction of CBD leading to biliary stasis, bacterial overgrowth, suppuration and biliary sepsis
Presentation: fever, RUQ pain, jaundice, elevated liver tests and can be septic (low BP and tachycardia)
Management: antibiotics and immediate ERCP to relieve the obstruction and retrieve the stones from the bile duct
Common organisms infecting duct: E. coli, Klebsiella, Pseudomonas, Enterococcus, B. fragilis, Proteus
What is the presentation of pancreatitis (gall stone related)? What is the management?
Pancreatitis - gall stone passes through or obstructs the pancreatic duct (which joins the CBD at the Ampulla of Vater (Sphincter of Oddi))
Presentation: Epigastric pain that radiates to the back, nausea, vomiting, and may have fever, low BP and tachycardia
Diagnostics: Elevated lipas (and amylase), may have elevated liver tests and bilirubin
Management: narcotics, IV fluids, ERCP for stone removal?
What is the treatment for pruritus?
Pruritus Management
- Sedating antihistamines and cholestyramine
- Rifampin, naloxone or naltrexone
- Plasmapheresis, liver transplantation
What is the clinical presentation, the confirmatory test and management of PBC?
Primary Biliary Cirrhosis - cholestasis (Increased ALP) with no significant alcohol, or drug hx, other chronic liver dx and normal bile ducts on ultrasound
- Chronic inflammation and fibrous obliteration of intrahepatic bile ductules
- Likely autoimmune
- Affects mainly middle-aged women
Clinical Presentation
- Often asymptomatic
- Fatigue and pruritus are common
- Sicca syndrome = dry eyes and dry mouth
- Frequently have other autoimmune diseases
- Metabolic bone disease is common
- If cirrhotic can progress to liver failure and may develop cirrhosis
Diagnostics
- Anti-mitochondrial antibodies (AMA) 95% specificity and sensitivity
- Increased IgM
Management
- Ursodeoxycholic acid (UDCA)
- Must be separated from cholestyramine by 2 hours before and after
What is the clinical presentation, the confirmatory test and management of PSC?
Primary Sclerosing Cholangitis - inflammation of biliary tree leading to scarring and lumen obliteration
Clinical presentation: often insidious, may present with fatigue and pruritus, metabolic bone diseae, can progress to cirrhosis
Diagnosis:
- Elevated ALP in presence of IBD
- AMA should be negative
- MRCP shows strictures and areas of dilatation
Management: liver transplant is only life saving therapy
- Higher risk of malignancies: Colorectal neoplasia, cholangiocarcinoma, gall bladder cancer
How is Hepatitis A transmitted? What are some RFs for contraction of the virus?
Hepatitis A
- Transmission is fecal-oral but can be seen in IVDU
- RFs: eating contaminated foods in endemic countries (ex. raw seafood), insufficient hand washing methods in food handlers, anilingus activity
How is Hepatitis B transmitted and what are some RFs?
Hepatitis B
- Transmission: vertical (mother to child at birth), horizontal (between infected children), parenteral (through exposure to infected blood ex. IVDU) or sexual
- RFs: multpile sexual partners, MSM, IVDU, infected mother, HIV positive, people in careers that exposue them to human blood/bodily fluid, travel to HBV endemic countries
How is Hepatitis C transmitted and what are some RFs?
Hepatitis C
- Blood borne transmission
- RFs: IVDU, reception of clotting factors before 1987, blood or organ donation before 1992, iatrogenic, traditional medicine practices, tattoos and piercings, sexual transmissions, vertical transmission
What are the 3 clinical presentations of alcohol related increased hepatocellular liver enzymes?
Alcohol Abuse and the Liver
- Steatosis (fatty liver) and/or steatohepatitis (fat and inflammation) = fatty infiltration on U/S, AST>ALT, ALT should not be >300, increased GGT, may be macrocytic, IgA often elevated
- Alcoholic Hepatitis = jaundice, hepatomegaly, RUQ pain, ascites, hepatic encephalopathy, fever,
- Cirrhosis
How is alcohol induced liver dysfunction prognosticated and what are the options for therapy?
Alcoholic Hepatitis
- Prognosis predicted by Maddrey Discriminant Function or Model for End-Stage Liver Disease (MELD)
Therapy
- Abstinence from further alcohol use (6 mths required for transplantation qualification)
- Prednisone 40 mg daily for one month
Describe the coures of Hepatitis B in terms of the immune tolerant, and clearance phase, inactive residual phase and reactivation.
Explain the meaning of a positive result of each of the following components of HBV serology.
HBsAg
Anti-HBs
Anti-HBc
IgM Anti-HBc
IgG Anti-HBc
HBeAg
Anti-HBe
HBV Serology
+ HBsAg = acute/chronic infection
+ Anti-HBs = immunity (vaccine or natural)
+ Anti-HBc (total) = exposure to virus (ongoing, past or acute)
+ IgM Anti-HBc = acute infection (+ HBsAg)
+ IgG Anti-HBc = natural immunity (- HBsAg)
+ HBeAg = replication (immune tolerant or immune clearance phase)
+ Anti-HBe = virus entering decreased replication (inactive residual or reactivation phase)
Describe the type of liver masses shown in the image attached.
- Simple cysts (arrows) on US
- Complex cysts due to Echinococcus with daughter cysts (arrow) on CT
- Liver abscesses with ring enhancement (arrows) on CT
- Hemangioma with puddling of contrast at peripheray (arrows) on CT
- Focal Nodular Hyperplasia (FNH) with central scar (arrow) on MRI
- Adenoma complicated by hemorrhage (arrow on CT)
Interpret the viral serology.
- anti-HAV antibody (total) positive
- HBsAg positive
- anti-HBs antibody negative
- anti-HCV antibody negative
Viral Serology
- anti-HAV antibody (total) positive = measurement of both IgM and IgG Abs to the virus, positive results could indciate immunity from a past infection or vaccination (IgG Abs)
- Acute infection = IgM anti-HAV antibody
- HBsAg positive = exposed to virus, acute or chronic infection
- anti-HBs antibody negative = not immune to HBV
- anti-HCV antibody negative = no HCV infection
Interpret the viral serology
- anti-HAV IgM positive
- anti-HBc total positive
- anti-HBc IgM negative
- HBVDNA negative
- anti-HDV negative
Viral Serology
- anti-HAV IgM positive: indicates acute (Hep A) infection
- anti-HBc total positive: indicates exposure to the virus
- anti-HBc IgM negative: no acute infection ongoing
- HBVDNA negative: no Hep B viral replication ongoing
- anti-HDV negative: no Hep D infection
What clinical signs or lab tests would be concerning for the possible development of acute liver failure (ALF)? How do you define ALF?
ALF
Clinically:
- Hepatic encephalopathy
- Jaundice
- High INR
Definition:
- Evidence of coagulation abnormality (INR >1.5) AND there must be encephalopathy in the patient without pre-existing cirrhosis AND an illness that has been <26 wks duration.
What malignancy are Hepatitis B patients at an elevated risk for?
Hepatocellular Carcinoma (HCC)
Interpret the Viral Serology
- anti-HAV (total) Ab positive
- HBsAg negative
- anti-HBs negative
- anti-HCV Ab negative
Viral serology
- anti-HAV (total) Ab positive: exposure to Hepatitis A, could be immune, could be acute infection
- HBsAg negative: no Hep B infection
- anti-HBs negative: no immunity to Hep B
- anti-HCV Ab negative: no Hep C
Interpret the viral serology
- anti-HAV (total) negative
- HBsAg negative
- anti-HBs positive
- anti-HBc (total) positive
- anti-HBc IgM negative
- anti-HCV Ab positive
Viral Serology
- anti-HAV (total) negative: no Hep A
- HBsAg negative: no acute infection
- anti-HBs positive: Hep B immunity
- anti-HBc (total) positive: exposure to Hep B virus
- anti-HBc IgM negative: no acute infection to Hep B ongoing
- anti-HCV Ab positive: Hep C infection; confirm with HCVRNA
What is the management for Hepatitis C pts?
Hep C Management
- Direct acting anti-virals ex. Harvoin and Holkira PAK
- Manage potential cirrhosis
What is the management for cirrhosis?
Cirrhosis
- LOW SODIUM DIET (<2000 mg)
- NO alcohol
- Avoid NSAIDs
- Diuretic for ascites; monitor electrolytes and creatinine
Manage complications if they arise..
- Endoscope and banding for bleeds
- Octreotide to decrease acute bleeds
- Vaccination for Hepatitis A
