Exam 5 Flashcards
Cirrhosis
What is Wilson’s Disease?
Excess accumulation of copper (ATP7B mutation)
Copper is deposited in:
- Liver
- Kidneys - Joints
- Brain (i.e. basal ganglia)
- Eyes (i.e. corneas: Kayser Fleischer ring)
Hepatocellular Carcinoma
- Notice the cirrhotic liver around the carcinoma
Hepatitis B transmission
Blood and Sex
Blood (needles/IVDU, old transfusions), Sex, vertical transmission (mom to baby)
Direct Bilirubin
Direct = Conjugated
Conjugated Bilirubin is excreted in the urine
Functional unit of the liver
Lobule
- Portal tract (triad)
- Hepatocytes
- Central Vein
What is Hereditary Hemochromatosis
Excess accumulation of Iron (bronze diabetes).
- Due to low levels of Hepcidin.
- Hepcidin lowers iron absorption by reducing iron transport across gut mucosa and reduces iron exit from the liver.
Pathology?
Hereditary Hemochromatosis
- Autosomal recessive disorder of the HFE gene
- Leads to excessive intestinal absorption of iron from low Hepcidin
Classic triad
- Cirrhosis
- Diabetes mellitus
- Increased skin pigmentation, AKA, bronze diabetes.
Indirect Bilirubin
Indirect Bilirubin = Unconjugated Bilirubin
- Has not been conjugated in the liver yet (pre-hepatic bilirubin)
- Bound to albumin, which makes it slightly less toxic than if it wasn’t bound
(Total - Direct = Indirect)
Kuppfer cells
Macrophages that sit in the sinusoids
Little Kups of inflammation that cause big problems if you knock them over
Hepatitis C transmission
Blood (old transfusions, IV drug/needles)
What happened here?
Primary Sclerosing Cholangitis (slide of what was the portal triad)
- Bile duct is destroyed and replaced with fibrosis
- Mara Rendi says need to be able to recognize
Metastatic Carcinoma invading the liver
- Notice the normal liver architecture around the cancer (no cirrhosis)
Treatment for Wilson’s Disease
copper chelation and inhibition of copper absorption
What’s going on here?
Chronic Cholecystitis
(Thick Wall)
Diagnosis and Treatment for HH
Dx:
- increased serum iron
- increased transferrin saturation
- increased ferretin levels
Tx: phlebotomy to reduce iron load
Alpha-1-antitrypsin deficiency (A1AT)
Can’t inactivate neutrophil elastase, so it goes crazy and runs around the lung and liver destroying tissues.
- function of A1AT is to inhibit the action of destructive neutrophil proteases, particularly in the lung.
- Autosomal co-dominant
- Can lead to liver and lung disease
Stellate Cells
Store vitamin A
Make collagen
Stellate Stalactites: Make fibrotic stalactites in the liver leading to cirrhosis
Hepatitis E main points
Fecal oral transmission Bad in pregnancy
Hepatitis D main points
Transmission: Blood and Sex
Only replicates if you already have hepatitis B already
- Up to 20% mortality if you have both
Progression of liver damage from alcohol
Alcoholic Liver Disease–>alcoholic hepatitis–> alcoholic cirrhosis–> Increased risk of liver cancer
Hepatitis B
- Transmitted via sex, blood (needles), vertical transmission (mom to baby)
- Can be clinical or subclinical infection
- 5-10% will go on to chronic Hepatitis
- 5-10% of those –> cirrhosis & cancer
- Immunization available
- No curative treatment
Hepatitis C
Hepatitis C(hronic)
- Transmitted via blood (transfusion, IV drug/needles) 50% of the time will go on to chronic hepatitis
- Not usually a problem until it progresses (elevated LFT’s on routine lab work
- Curative treatment available: almost $100,000 (Harvoni)
- Can lead to cirrhosis and increased risk of liver cancer
Hepatitis A
A for Acute & Asymptomatic
- fecal oral: contaminated food & water, restaurants, daycares
- Often undetected, can get better on its own
- AST/ALT: High 100’s low 1000’s
- Does not cause chronic liver disease
Kayser Fleischer ring: copper around cornea from Wilson’s Disease
Bronze Diabetes
Heriditary Hemochromatosis
Increased iron saturation leads to darkening of the skin and diabetes. Also see iron deposition throughout the body.
Elevated transferrin saturation
Chronic Cholecystitis
(Thick Wall)
A1AT causes
Liver and Lung Disease
If you get cancer in the gallbladder is can?
easily break through the thin wall and/or invade the liver
Gall stones (looks like in the common bile duct)
Gallstones can lead to?
Acute Cholecystitis
- Acute obstruction of duct by stone leads to edema, congestion, hemorrhage and exudates.
- Impacted stones cause ulceration.
Chronic Cholecystitis
Thick gallbladder wall!
- Multiple episodes of inflammation cause gallbladder thickening and contraction with variable wall thickness and appearance.
Carcinoma of Gallbladder
Porcelain Gallbladder
- With longstanding inflammation gallbladder wall becomes fibrotic and calcified : “porcelain gallbladder”
- Associated with gallbladder carcinoma in 20% of cases
A) Mass of carcinoma
B) Gall stones
Porcelain Gallbladder
Worry about Gallbladder carcinoma
Consequence of thin gallbladder wall?
Carcinoma of the gallbladder has a really poor prognosis, because it usually presents at a late stage
- usually no symptoms
- easily spreads through thin wall of gallbladder out into the body or into the liver
Label
Liver Lobule
Function of Hepatocytes
Protein Synthesis: (Albumin, Clotting & Anticoag factors)
Storage: (Carbohydrates, Lipids, Vitamins)
Bile Production
Detoxification:
- Ammonia
- Bilirubin
- Drugs
- Toxins
Cell Type?
Hepatocytes
Portal Triad (Portal Tract)
A) Portal Vein (venous blood from GI tract)
B) Bile Duct
C) Hepatic Artery (brings O2 rich blood to liver)
Name and Function
Liver Zones & Importance of Each
Hepatitis virus types (DNA or RNA)?
Hep B is DNA virus
All others are RNA
ground glass hepatocytes: Hepatitis B
Diagnosis?
Chronic Hepatitis C
- Lymphoid aggregates or follicles with germinal centers in the portal areas
- Clear areas are steatosis (fat in hepatocytes)
- Mara Rendi says “must know histology”
What’s going on here?
Chronic Hepatitis C
Pathology of Alcoholic Liver Disease
- Fat accumulation in hepatocytes (steatosis)
- Mallory Bodies
- Progresses to Fibrosis & Cirrhosis
A) Fat
B) Inflammatory aggregates (ants)
C) Mallory Bodies (smudgy pinks)
- alcohol is damaging liver cells and cytoskeletal elements get broken down
- these cytoskeleton peices clump up (bright pink piles of debris)
Non-Alcoholic Steatohepatitis (NASH) Pathology
Looks like Alcoholic Fatty Liver Disease without the Mallory bodies
Characteristic pathology with zone 3 hepatocellular injury pattern
- Steatosis
- Lobular inflammation
- Fibrosis
Associated with insulin-resistance
Primary Biliary Cirrhosis (PBC)
Key Point to remember: Bile ducts in the portal triads get destroyed –> can’t get bile out –> inflammation –> cirrhosis
- Middle-aged females
- Associated with autoimmune disorders
- Positive anti-mitochondrial antibodies (AMA) and elevated alkaline phosphatase.
- Florid duct lesion on pathology (granulomatous/inflammation attack on bile ducts)
Primary Sclerosing Cholangitis (PSC)
Destruction of the bile ducts
- Commonly affects young males
- 70% patients have coexisting idiopathic inflammatory bowel disease (UC)
- Elevated alkaline phosphatase and bilirubin
- ERCP shows beaded strictures of the bile ducts
- Risk of cholangiocarcinoma
Diagnosis?
Primary Sclerosis Cholangitis: Beads on a string
Diagnosis?
Primary Sclerosing Cholangitis
- Fibroinflammatory destruction of the bile ducts leading to Concentric periductal (“onion-skin”) fibrosis
- Eventual fibroobliteration of the bile ducts
- Cirrhosis develops subsequently
Pathology?
What gene is mutated?
Kayser-Fleisher (copper) rings = Wilson Disease
- Autosomal recessive disorder of copper metabolism resulting in accumulation of copper in organs including liver, brain, and eye.
- ATP7B mutation: can’t put copper into bile
- See decreased serum ceruloplasm
Main Functions of the Liver
Stores: B12, copper, iron, A, D, E, K
Detoxifies: bilirubin, alcohol, drugs, toxins, Ammonia
Synthesizes: Transport proteins, plasma albumin, clotting factors, urea, glycogen, cholesterol, phospholipids, bile salts, lipoproteins
Liver Function Tests and What They Generally Indicate
AST/ALT
- Elevated = Active damage to hepatocytes (happening right now)
Alkaline Phosphate
- Elevated = Biliary obstruction
Albumin & Clotting Factors
- Elevated = Hepatocytes are dead and not making things
- Clotting factors have a shorter half life than albumin and are thus low first
Steps of Bilirubin conjugation image
Label the boxes
LFT’s in Acute Hepatocyte Necrosis
- Type of Hyperbillirubinemia?
- Urine Bilirubin?
- Aminotransferases?
- Alkaline Phosphatase?
- Prothrombin/INR?
- Albumin?
- Conjugated (direct)
- Urine Bilirubin: Present
- Very High AST/ALT
- Elevated Alkaline phosphatase (< 3 x normal)
- Prothrombin/INR could be elevated or normal, depending on severity
- Albumin would be normal (does not become elevated until hepatocytes dead for a while, because of long half-life)
LFT’s in Cholestasis
- Type of Hyperbillirubinemia?
- Urine Bilirubin?
- Aminotransferases?
- Alkaline Phosphatase?
- Prothrombin/INR?
- Albumin?
- Conjugated (Direct Bilirubin)
- Urine Bilirubin: present
- AST/ALT: slight elevation
- Alkaline Phosphatase: Very High ( > 3x normal)
- Clotting: Normal
- Albumin: Normal
LFT’s in Gilbert’s Syndrome
Type of Hyperbillirubinemia?
Urine Bilirubin?
Aminotransferases?
Alkaline Phosphatase?
Prothrombin/INR?
Albumin?
Gilbert’s syndrome: decreased UGT1A1 enzyme activity
- Unconjugated (indirect Bilirubin)
- Urine Bilirubin: absent
- AST/ALT: normal
- Alkaline Phosphatase: normal
- Clotting: Normal
- Albumin: Normal
Gilbert just can’t conjugate anything…
LFT’s in Cirrhosis
- Type of Hyperbillirubinemia?
- Urine Bilirubin?
- Aminotransferases?
- Alkaline Phosphatase?
- Prothrombin/INR?
- Albumin?
- Conjugated = Direct Bilirubinemia
- Urine Bilirubin: Present
- AST/ALT: slight elevation
- Alkaline Phosphatase: slight elevation to normal
- Clotting (PTT/INR): Slow/Long
- Albumin: Low
LFT’s in increased UCB (e.g. RBC damage, neonatal jaundice)
- Urine Bilirubin?
- Aminotransferases?
- Alkaline Phosphatase?
- Prothrombin/INR?
- Albumin?
- Urine Bilirubin: No
- AST/ALT: slight elevation in AST, ALT: normal
- because dying RBC’s release AST
- Alkaline Phosphatase: normal
- Clotting: Normal
- Albumin: Normal
What does each of these tell you?
- Urine Bilirubin
- Aminotransferases
- Alkaline Phosphatase
- Prothrombin/INR
- Albumin
- Urine Bilirubin: Is it conjugated (post-hepatic)
- Aminotransferases: Are liver cells being actively damaged
- Alkaline Phosphatase: Is there obstruction or bone breakdown
- Prothrombin/INR: Are hepatocytes dead
- Albumin: Have hepatocytes been dead for a few days
Palmar Erythema & Spider Angiomata mean?
Cirrhosis (consequences of excess estrogen)
The Liver clears/detoxifies estrogen
Asterixis
Flapping tremor of the extended hands
Sign of Hepatic Encephalopathy (Ammonia)
Caput Medusae
Consquence of Portal Hypertension
Cirrhosis
Trichrome stain (where collagen is blue)
Hepatocellular Adenoma
- Associated with OCP (usually young women)
- Regression after discontinuation of OCP
- Benign, usually not associated with cirrhosis
Cirrhosis
Gilbert’s Syndrome
A benign condition where unconjugated bilirubin rises in the presence of stress (e.g. fever, sepsis, fasting and staying up all night)
- episodic jaundice, with no other symptoms
- autosomal recessive
Pregnant women with itching of palms and soles
Think Intrahepatic Cholestasis (stasis of bile) of Pregnancy (ICP)
- flow of bile (containing conjugated bilirubin) is stopped somewhere between hepatocytes and duodenum
- mechanism not really understood (could be hormonal)
- can see tea colored urine (conjugated hyperbilirubinemia)
A woman in her third trimester of pregnancy presents to your clinic with tea-colored urine, and several days of intense itching of her palms and soles.
What is the appropriate treatment for this condition?
Ursodeoxycholic acid (you’re so deoxy, Cholic….)
- reduces itching, bilirubin serum bile acid
Inducing her or C-section are common options
- especially if her serum bile acid > 40 umol/L, due to the increased risk of complications it causes
Treatment of Acetaminophen Overdose
Acetylceysteine
Restores pool of reduced Glutathione (GSH), which detoxifies toxic metabolite before it can do damage
