Liver Disorders Flashcards
Physiologic liver functions
lipid, carb, protein metab clotting factor production detox storage of vitamins and glycogen bile processing and secretion
Liver composition and role
Composed of hepatocytes, bile ducts, blood vessels
Central organ of metabolic homeostasis
Large functional reserve and regenerative capacity
Causes of chronic liver dz
Hep C, EtOH Induced, Non-EtOH fatty liver dz, Hep B
Also, blood flow abnormalities, usually INTRAHEPATIC lfow probs (from cirrhosis occlusion)
Grade and Stage
grade = amount of infl and injury Stage = amount of fibrous tissue deposition (on liver biopsy)
Liver Failure (info/cause/3 types)
Caused by acute or chronic failure via cirrhosis
NEED TO HAVE 80-90% loss of function before you see sx
1) massive necrosis, 2) cirrhosis (scarred liver) 3) dysfunction +/- cirrhosis or necrosis
Liver Failure (pres)
Ascites, jaundice, scleral icterus
Spider angioma, palmar erythema, gynecomastia
Coagulopathy, encephalopathy, renal failure
Cirrhosis (info/cause/pres)
Scarred liver, common end point to many chronic liver dz
Result of recurring death of hepatocytes and deposition of ECM
Pres with 1) PORTAL HTN (splenomegaly, eso varcies, ascties, periumbilical medusae, encephalotphay
2) JAUNDICE (bilirubin production > clearance)
3) CHOLESTASIS (impaired bile flow)
Cirrhosis (diagnx)
Diffuse fibrous septation that divides the liver parenchyma in NODULES
Hepatitis (Acute)
Causes and Infl cell profiles
New onset (
Hepatitis (def)
Inflammatory dz of hepatocytes (liver) and characterized by presence of inflammatory cells in the tissue of the liver
Hepatitis (Chronic)
Causes and accumulations
Sx dz for >6 mos
Common causes CHRONIC VIRAL (moslty C, B, D), autoimmune, drug injury
SPOTTY injury (looks less severe than acute)
Grade: amount of infl
Stage: amount of fibrosis
Cytoplasmic accumulations: fat (steatosis), bile (cholestasis), iron (hemosiderosis), Copper (Wilson), Viral (viral hepatitis GROUND GLASS HISTOL)
VIRAL HEPATITIS Hep C (info)
Major cause of liver dz in US
Genetically unstable (many genotypes and subtypes)A
Anti-HCV Ab are made BUT are not neutralizing so NO VACCINE
Risks: IV drugs, multiple partners, surgery, needle injury, multiple HCV contacts
VIRAL HEPATITIS Hep C (pres/diagx/treat)
85% acute to chronic dz, often asymptomatic if acute
Diagnx: Lymphoid aggregates (see chronic hep)
Treat: GOAL: remain HCV RNA neg for 12 WEEKS AFTER STOPPING TX
Genotype 1: SVR 40-70% (PegIFN, Ribavarin, protease inhib)
Genotype 2 & 3: PegIFN, Ribavarin
Hepatotropic viruses
hepatocyte is primary target
SVR? (for Hep)
Sustained Virological Response = Cure
VIRAL HEPATITIS Hep B (cause/diagnx/treat)
Major cause of liver dz WORLDWIDE
dsDNA virus (can integrate into genome)
Transmitted via blood, VACCINE EXISTS
Diagnx: GROUND GLASS HEPATOCYTES, SANDED NUCLEUS
Treat: IFN for 1 yr (flu-like side fx), nucleoside/tide (Tenofovir)
IF: HBsAg > 6 mos, HBV DNA > 10^5, persistent or intermittent high ALT and AST (cirrhosis)
VIRAL HEPATITIS Hep B (pres MARKERS)
Most ADULTS recover (5% progress to chronic) - more children do
HBsAg (surface antigen): ACTIVE INFX
HBsAb: IMMUNITY to HepB
HBcAb: ACTIVE or PRIOR infx
HbeAg: ('e' antigen) HIGH VIRAL LOAD
HBeAb: LOW VIRAL LOAD
HBV DNA: ACTIVE VIRAL REPLICATIONVIRAL HEPATITIS
Hep D
cannot replicate, COMPLETELY DEPENDENT ON HEP B COINFECTION, potentiates effects of Hep B, parenteral transmission
Pres: increased risk of fulminant Hep, + activity and faster progress to end-stage liver dz
Diagnx: may show increased plasma cells
VIRAL HEPATITIS
Hep A
Oral/fecal transmission (and bad strawberries)
VACCINE available
Does NOT progress to chronic
Diagnx: IgM Ab in serum
VIRAL HEPATITIS
Hep E
Oral/fecal trans
HIGHER MORTALITY in PREGNANT WOMEN
Acute
Diagnx: Igm/IgG Ab in serum
AUTOIMMUNE
Autoimmune Hep
Immune attack of hepatocytes, 78% women, usually with autoimmune dz
Pres: variable
Diagnx: serology: AutoAb (ANA, ASMA, Anti-LKMB) & elevated IgG but PLASMA CELL RICH
Treat: Immune suppression (steroids, Azathioprine), treat for a few years after normal to prevent relapse
AUTOIMMUNE
Primary Biliary Cirrhosis
(info/pres)
Bad name: not necessarily cirrhosis
Immune attack of INTRAHEPATIC ONLY small caliber bile ducts
nearly ALWAYS middle aged women
Pres: INSIDIOUS ONSET WITH PRURITUS BEFORE JAUNDICE
AUTOIMMUNE
Primary Biliary Cirrhosis (PBC)
(diagnx/treat)
Elevated ALP, IgM (GGT, bilirubin)
AMA in 90%
Granulotamous lympocytic cholangitis, florid duct lesion, eventual ductopenia
Treat: URSODEOXYCHOLIC ACID (aka ursodiol, slows prog)
Fair prognosis (25% with liver failure at 10 yrs)
AUTOIMMUNE
Primary Sclerosing Cholangitis
(info/pres/treat)
Immune attack of INTRA- AND EXTRAHEPATIC bile ducts (usually larger caliber)
M>F, 70% have UC, increased risk for cholangiocarcinoma
Asymptomatic (elevated ALP) –> progresses to fatigure, pruritus, jaundice
Treat: no good tx, manage progression
AUTOIMMUNE
Primary Sclerosing Cholangitis
(Diagnx)
Persistent ALP elevation and IgM
Diagnx with cholangiography (ALTERNATING BILIARY STRICTURES AND DILATION)
No specific serology
PERIDUCTAL “ONION SKIN” FIBROSIS –> progresses to fibrous obliteration of bile ducts
DRUG INDUCED (general)
common cause with many patterns of injury
Intrinsic: all affected in dose related way
Idiosyncratic: only certain people have bad reaction
Treat: discontinue drug
DRUG INDUCED
Acetaminophen
Intrinsic (all affected), often in suicide attempts
Major casue of ACUTE liver failure
Injury in ZONE 3 (cnetral vein), CONFLUENT CENTRILOBULAR COAGULATIVE NECROSIS
Treat: Remove drug (lavage, charcoal), N-acetylcysteine
METABOLIC LIVER DZ
(here adults, but more common in kids)
EtOH related Steatohepatitis vs Non EtOH
EtOH: blocks lipid clearance (beta-oxidation of lipids into CO2 and ketones) and stimulates lipogenesis
Non-EtOH (NASH): assoc with metabolic syndrome (obesity, DM) fatty liver –> decreased lipolysis
METABOLIC LIVER DZ
EtOH/non-EtOH Steatohepatitis (pres/diagnx/treat)
Steatosis = lipid production>clearance (may progress to steatohepatitis)
Diagnx: ballooned degeneration, PMN infiltrates pericentral/perilobar fibrosis
EtOH: Mallory Bodies (AST AT LEAST 2s ALT)
Treat: life modification
METABOLIC LIVER DZ
Hereditary Hemochromatosis
(cause/pres)
Iron overload (genetic), AR, HFE mutation [C282Y and H63D], M>F
Pres: 44% with joint stiffness
Hyperpigmentation, Diabetes, Hypothyroidism
Hypogonadism, Cardiomyopathy, Cirrhosis
METABOLIC LIVER DZ
Hereditary Hemochromatosis
(diagnx/treat)
Iron stain (prussian blue), Fe in HEPATOCYTES, NOT Kupffer cells (would be hemosiderosis) HPE gene testing, + ferrtin, + transferrin sat., + Fe sat. TREAT: Tx phlebotomy, endpoint: serum ferritin at 50ng/ml - Fe intake, genetic counseling, if anemic: chelation
METABOLIC LIVER DZ
Wilson Dz
Copper overload (genetic), AR, ATP7B mutation (transporter for bile excretion of Cu)
Pres: Liver dz and neuropsych dz
Diagnx: Copper stain (Rhodamine)
Treat: chelators (D-penacillinamince, tirentine, then transition to oral zinc
METABOLIC LIVER DZ
Alpha-1-anti-trypsin
Dec produciton of A1AT (protease inhib), AR, PiZZ dz genotype (PiMZ heterozygote is normal)
Pres: assoc with emphysema (10% have liver dz)
Diagnx: PAS-positive, diastase resistant pink globules of A1AT in hepatocytes
LIVER MASSES Hepatocellular Carcinoma (malignant)
Most common malignant liver tumor
Almost always in pts with chronic liver dz (eg Hep B, C, EtOH), dismal long term survival
Diagnx: THICKENED HEPATIC PLATES (trabeculae), UNPAIRED ARTERIOLES (neovasculatization), ELEVATED AFP
Treat: resect/transplant and if not: trans-arterial chemoembolization
LIVER MASSES
Malignant Cholangiocarcinoma
Neoplasm of bile ducts (intra- or extrahepatic), PSC is major risk factor, dismal long tern survival (25% at one year)
Diagnx: GLAND FORMING WITH DESMOPLASIA
LIVER MASSES
Metastases
Common place for metastases, well circumscribed, most tumors in liver are metastatic of other cancers
LIVER MASSES
Hemangioma (Benign)
MOST COMMON OF ALL HEPATIC TUMORS
F>M, 4:1
Pres: usually small and asymptomatic, vague RUQ pain, early satiety, nausea, vomiting
Diagnx: spongy appearance, dilated thin walled vascular spaces
Treat: resect for larger ones
LIVER MASSES
Focal Nodular Hyperplasia (Benign)
F>M, 4:1, arise due to local vascular flow anomaly, hepatocyte mass
Pres: usually small and asymptomatic, vague RUQ pain, early satiety, nausea, vomiting
Looks cirrhotic but focal, CENTRAL STELLATE SCAR, ENLARGED ABNORMAL ARTERIOLES
LIVER MASSES Hepatocellular Adenoma (Benign)
Women of childbearing age, ORAL CONTRACEPTIVE USE, LOW RISK OF MALIGNANCY, no chronic liver dz
Pres: asymptomatic or RUQ pain, risk of rupture/hemorrhage into abd (if v large)
Diagnx: hepatocyte proliferation (looks like hepatocellular carcinoma)
