Liver Flashcards by Denisse Tiangco

Jaundice, cholestasis
Hypoalbuminemia
Hypoglycemia
Hyperammonia (defective urea cycle function)
Palmar erythema (local vasodilation)
Spider angioma (central pulsating dilation of arteriole with small vessel radiation)
Hypogonadism (hyperestrogenemia) and gynecomastia
Gynecomastia
Weight loss
Muscle wasting

Severe Hepatic Dysfunction

How well did you know this?

Not at all

Perfectly

Ascites with peritonitis
Splenomegaly
Esophageal varices
Hemorrhoids
Caput medusae

Portal hypertension associated with Cirrhosis

How well did you know this?

Not at all

Perfectly

Coagulopathy
Hepatic encepalopathy
Hepatorenal syndrome
Portopulmonary hypertension
Hepatopulmonary syndrome

Complications of Hepatic failure

How well did you know this?

Not at all

Perfectly

Hepatocyte integrity
(Elevation: Liver disease)

AST
ALT
LDH

How well did you know this?

Not at all

Perfectly

Biliary excretory function

Serum bilirubin (Total, Direct, Delta:linked to albumin)
Urine bilirubin
Serum bile acid
Plasma membrane (damage to bile canaliculi)
Serum alkaline phosphatase
Serum gamma glutamyl transpeptidase
Serum 5’ nucleotidase

How well did you know this?

Not at all

Perfectly

Hepatocyte function

Serum albumin
Prothrombin time (V,VII,X,PT,fibrinogen)
Hepatocyte metabolism: 
Serum ammonia
Aminopyrine breath test (heptic demethylation)
Galactose elimination (IV injection)

How well did you know this?

Not at all

Perfectly

Most severe consequence of liver disease, end point of progressive damage
Loss of 80-90% hepatic function
Insidious piecemeal destruction, repetitive waves of parenchymal damage or sudden, massive destruction

Hepatic failure

How well did you know this?

Not at all

Perfectly

Drugs or viral hepatitis
Clinical hepatic insuff to hepatic enceph within 2-3 weeks
MASSIVE HEPATIC NECROSIS
Liver transplant

Acute Liver Failure with Massive Hepatic Necrosis

How well did you know this?

Not at all

Perfectly

Most common route to hepatic failure, endpoint of chronic liver damage
Parenchymal, biliary or vascular in origin
Ends in cirrhosis

Chronic liver disease

How well did you know this?

Not at all

Perfectly

Acute liver failure extending more than 3 months

subacute

How well did you know this?

Not at all

Perfectly

Viable hepatocyte but unable to perform metabolic function
Mitochondrial injury in Reye syndrome
Acute Fatty Liver of pregnancy
Toxin mediated injury

Hepatic dysfunction without overt necrosis

How well did you know this?

Not at all

Perfectly

Bile two major functions

1 primary pathway for elimination of bilirubin, chole and xenobiotics
2 emulsification of fat in gut by bile salt and phospholipid

How well did you know this?

Not at all

Perfectly

Yellow discoloration of skin and sclerae icterus occurs when system retention of bilirubin exceeds

2 mg/dl jaundice

How well did you know this?

Not at all

Perfectly

Systemic retention of bilirubin + BILE SALTS AND CHOLESTEROL

Cholestasis

How well did you know this?

Not at all

Perfectly

Oxidize heme to biliverdin

Biliverdin is reduced to bilirubin by

Heme oxygenase

Biliverdin reductase

How well did you know this?

Not at all

Perfectly

Bilirubin hepatocyte uptake

Carrier mediated uptake at sinusoidal membrane
Cystosolic protein bindingn and delivery to ER
Conjugation with one or two molecules of glucoronic acid by bilirubin UDP GT uridine diphosphate glucuronosyl transferase
Excretion of water soluble nontoxic bilirubin glucuronides into bile (conjugated)

How well did you know this?

Not at all

Perfectly

Conjugated bilirubin is deconjugated by gut bacterial B glucuronidase and degraded to

colorless urobilinogen

How well did you know this?

Not at all

Perfectly

Physiologic jaundice or neonatal jaundice happens bec hepatic machinery for bilirubin conjugation and excretion only matures at around

2 weeks

How well did you know this?

Not at all

Perfectly

Common 7% benign heterogenous inherited mild fluctuating unconjugated hyperbilirubinemia
Dec hepatic levels of glucorosyltransferase from mutation in encoding gene
No morbidity

Gilbert Syndrome

How well did you know this?

Not at all

Perfectly

Autosomal recessive defect in transport protein for hepatocellular excretion of bilirubin glucuronides across canalicular membrane
Exhibit hyperbilirubinemia
Darkly pigmented liver from polymerized epinephrine metabolites
Hepatomegaly without functional problem

Dubin-Johnson Syndrome

How well did you know this?

Not at all

Perfectly

Enzyme in bile duct and canaliculi of hepatocyte

Elevated in cholestasis

ALP

How well did you know this?

Not at all

Perfectly

Hemolytic anemia
Resorption of blood from intestinal hemorrhage
Ineffective EPO syndrome (pernicious, thalassemia)

excess bilirubin production

predominantly unconjugated hyperbilirubinemia

How well did you know this?

Not at all

Perfectly

drug interference with membrane carrier system

diffuse hepatocellular disease (viral, drug induced)

reduced hepatic uptake

predominantly unconjugated hyperbilirubinemia

How well did you know this?

Not at all

Perfectly

physiologic jaundice of newborn

Impaired bilirubin conjugation

Predominantly unconjugated hyperbilirubinemia

How well did you know this?

Not at all

Perfectly

Def of canalicular membrane transporter Drug induced canalicular membrane dysfunction (ocp cyclosporine) Hepatocellular damage/toxicity

Dec hepatocellular excretion | Predominantly conjugated hyperbilirubinemia

Inflammatory destruction of intrahepatic bile duct (primary sclerosing, graft-vs-host, liver transplant) gallstone, ca of pancreas

Impaired intra or extra-hepatic bile flow | Predominantly conjugated hyperbilirubinemia

Most common cause of jaundice involving accumulation of unconjugated bilirubin

Hemolytic anemia

Most common cause of jaundice involving accumulation of conjugated bilirubin

Hepatitis intra or extrahepatic obstruction

``` Rigidity Hyperreflexia Nonspecific EEG Seizure ASTERIXIS (flapping tremor) nonrhythmic rapid ext and flex movement of head and extremities esp when arms are held in extension with dorsiflexed wrist ```

Hepatic | Encephalopathy

Factors contributing to hepatic enceph

severe loss of hepatocellular function | shunting of blood from portal to systemic circulation around chronically diseased liver

Key pathogenesis in hepatic enceph

Elevation in blood ammonia Impairing neuronal function and promoting generalized brain edema in acute Deranged neurotrasmitter production monoaminergic, opiodergic, y-aminobutyric acid and endocannabanoid system in chronic

Diffuse process characterized by fibrosis and conversion of normal liver architecture to structurally abnormal nodule

Cirrhosis

Cirrhosis main characteristics

1 fibrous septa - delicate bands or broad scars around lobules Long standing fibrosis is irreversible as long as vascular shunts are present, regression if cause reversed 2 parenchymal nodule - small to large, encircled by fibrous bands Preexistent hepatocyte displaying replecative senescence at time of fibrosis Newly formed hepatocyte capable of replication gives rise to ductular reactions at periphery of nodules 3 involvement of most of liver

3 processes central to pathogenesis of cirrhosis

Death of hepatocyte Extracellular matrix deposition Vascular reorganization

In cirrhosis this type of collagen is deposited in space of Disse instead of type IV

Type I & III

Major source of excess collagen in cirrhosis normally functioning as storage of Vitamin A Activate and transform to myofibroblast during fibrosis due to ROS, TNF, IL1 and lymphotoxin

Stellate cells of perisinusoid | Ito cells in space of Disse

stellate cells produce that initiate fibrosis formation

TGF B

Even in late stage disease this may happen significant restoration or remodelling due to dynamic process of ECM synthesis, deposition and resorption by metalloproteases

cirrhotic regression

Vascular lesions that contribute to liver function defect

Loss of sinusoidal endothelial fenestration and inc basement membrane formation -> thin walled sinusoid becoming fast flowing vascular channel -> impaired protein movement Portal vein-hepatic vein shunt Hepatic artery-portal vein shunt

Dominant intrahepatic cause of portal hypertension

cirrhosis

Inc resistance to portal flow and compression of central vein by perivenular fibrosis and parenchymal nodule Inc blood flow to portal vein from vasodilation of splanchnic circulation (hyperdynamic circulation) from inc NO from bacterial DNA Imposed arterial pressure on normally low pressure portal veins

Portal hypertension

Collection of excess fluid in peritoneal cavity at least 500 ml to be clinically detectable Serous, 3g/dL of albumin Serum ascites:albumin gradient >/= 1.1 g/dL scant mesothelial cell and mono

Ascites Neutrophilic -infection RBC -cancer Hydrothorax on right from peritoneal fluid seepage through diaphragm lymphatics

Ascites pathogenesis

Inc movement of intravascular fluid into spase of Disse by sinusoidal HTN and hypoalbuminemia Leakage of fluid from hepatic interstitium to peritoneum. Hepatic lymph flow >20l (normal 800-1000ml) which is rich in proteins and low in TAG Renal retention of Na and water 2 to hyperaldosteronism despite total body sodium mass more than normal

Principal sites of portosystemic shunt

Rectal veins CEJ veins Retroperitoneum and falciform ligament of liver (periumbilical and abdominal)

Renal failure without primary abnormality of kidney in severe liver failure bec splanchnic vasodilation and systemic vasoconstriction leading to dec renal blood flow of cortex Dec UO and inc BUN, Crea Hyperosmolar urine devoid of protein and abn sediment (low in sodium) vs RTN Tx: transplant, HD

Hepatorenal syndrome Exclude circulatory collapse

Pulmonary arterial HTN assoc with liver disease or portal HTN Excessive pulmo vasocon and vaso remodelling leading to R HF Most common clinical manifestation are

Portopulmonary HTN Hepatopulmonary HTN Dyspnea with severe arterial hypoxemia and cyanosis

Pathognomonic of hepatopulmonary HTN

Platypnea (easier breathing while lying down vs sitting and standing) Orthodeoxia (fall of arterial blood oxygen with upright posture)

Most common cause of drug induced acute liver failure

Acetaminophen

Agent that causes cholestasis in those who metabolize it slowly

chlorpromazine

Fatal immune-mediates hepatitis in persons exposed to this anesthetic

Halothane

Bland hepatocellular cholestasis without inflamm | OCP, anabolic steroid, ERT use

Cholestatic injury

Cholestasis with lobular inflamm and necrosis bile duct destruction Antibiotics Phenothiazine

Cholestatic hepatitis

``` Spotty hepatocyte necrosis (methyldopa, phenytoin) Submassive necrosis of zone 3 (acetaminophen, halothane) Massive necrosis (isoniazid, phenytoin) ```

Hepatocellular necrosis

Macrovesicular | Ethanol, methotrexate, corticosteroids, TPN

Steatosis

Microvesicular Mallory body Amiodarone Ethanol

Steatohepatitis

Periportal Pericellular fibrosis Methotrexate, isoniazid, enalapril

Fibrosis | Cirrhosis

Noncaseating epitheloid granuloma | Sulfonamide

Granulomas

Sinusoidal obstruction Obliteration of central vein (high dose chemo, bush tea) Budd-Chiari (OCP) Sinusoidal dilation (OCP, others) Peliosis hepatis: blood filled cavities not lined by epithelial cell (Anabolic steroids, tamoxifen)

Vascular lesion

``` Hepatic adenoma (OCP, anabolic) Hepatocellular CA (Thorotrast) Cholangiocarcinoma (Thorotrast) Angiosarcoma (Thorotrast, vinyl chloride) ```

Neoplasm

Nodular masses of liver separated by granulation tissue and scar Nodularity and scarring entire or patchy involvement Mononuclear infiltrates predominate all phases bec of T cell immunity Ballooning degeneration, empty cell with pale cytoplasm rupturing and undergoing necrosis cytolysis (dropped out appearance) and apoptosis eosinophilic shrunk hepatocyte If awat from portal tract and in parenchyma (lobar hepatitis) Central-portal bridging necrosis followed by parenchymal collapse

Hepatitis

Minimal or absent portal inflamm

Acute hepatitis

Dense MONONUCLEAR portal infiltrate of variable prominence Interface hepatitis Scarring Fibrous septa -> cirrhosis Dx

Chronic hepatitis Liver biopsy

Distinction between acute and chronic hep is based on

Pattern of cell injury Severity of inflammation Acute hep- less inflammation and more hepatocyte death than chronic

Hexagon centered on a central vein with portal tract at three of its apices Regions: periportal, midzonal, centrilobular

Hepatic lobule

Blood supply as reference with portal vessels at their base on the basis of distance from blood supply, 3 zones 1 closest to blood source 2 and 3 farther

Hepatic acinus

Appears before onset of symptom Peaks in overt disease Declines undetectable at 3-6 m

HBsAg

Does not rise until acute disease is over and not detectable for few weeks to months after disappearance of HBsAg May persist for life conferring immunity Basis for vaccination

Anti-HBs

Appear in serum soon after HBsAg Signify active viral replication Persistence indicates continued viral replication infectivity and progression to chronic hepatitis

HBeAg HBV-DNA DNA polymerase

Implies that acute infection has peaked and on the wane

anti-Hbe

Detectable in serum shortly before the onset of symptoms, concurrent elevation of serum AST ALT Replaced by IgG

IgM Anti-HBc

Accumulation of HBsAg in cytoplasm | Large pale finely granular pink cytoplasm inclusions on ER

Ground glass hepatocyte in chronic hep B

Fatty change from altered lipid metab Lymphoid infiltrates in portal tract with fully formed lymphoid follicle Bile duct injury by direct infection of cholangiocyte

Hepatitis C

Pathognomonic of yellow fever | Apoptosis of hepatocyte, eosinophilic

Councilman bodies

Only causes acute hepatitis

Hepa A | Hepa E

Cause chronic hepatitis

Hepa B, C, D

Inflammatory cells in both acute and chronic Hep | Difference in pattern of injury

T cell

Most important for grading and staging of disease used to decide whether px will undergo antiviral tx

Liver biopsy in chronic hep

``` sSRNA Hepatovirus, Picornavirus Fecal oral Incubation: 2-6 w Freq of chronic liver disease: Never Lab dx: Detection of serum IgM ```

Hepatitis A

``` Partially dsDNA Hepadnavirus Parenteral, sexual contact, perinatal Incubation: 4-26w Freq of chronic liver: 10% Dx: Detection of HBsAg or HBcAg ab ```

Hepatitis B

ssRNA Flaviridae Parenteral, intranasal cocaine use is risk factor Incubation: 2-26w Freq of chronic liver disease: 80% Dx: PCR assay for HCV RNA, 3rd gen ELISA for ab detection

Hepatitis C

Circular defective ssRNA Subviral particle in Deltaviridae Parenteral Incubation: 4-26w Freq of chronic liver: 5% coinfec, = 70% for superinfection Dx: Detection of IgM and IgG ab, HDV RNA serum, HDAg liver

Hepatitis D

``` ssRNA Hepevirus Fecal-oral Incubation: 2-8 weeks Freq of chronic liver: Never Laboratory diagnosis: PCR assay for HEV RNA, detection of IgM and IgG ```

Hepatitis E

Female, absent viral serology, inc IgG, high autoantibody, autoimmune disease (RA, Sjogren’s) Early phase of severe cell injury and inflamm followed by rapid scarring (early wave of hepatocyte damage and necrosis) Very severe hepatocyte injury with confluent necrosis Marked inflammation with advanced scarring Burned out cirrhosis with Little ongoing cell injury or inflamm Mononuclear infiltrate with abundant PLASMA CELL Responds to immunosuppresive therapy

Autoimmune hepatitis

Drugs that induce autoimmune hepatitis

Minocycline | Nitrofurantoin

Fatty liver disease (3)

Steatosis Hepatitis Fibrosis

Fat accumulation begins in centrilobular area | Small to large dropleta filling and expanding cell displacing the nucleus (central vein -> hepatocyte)

Hepatocellular steatosis

More pronounced with alcohol use than NAFLD

Steatohepatitis with ballooning, Mallory-Denk, neutrophil infiltration

Single or scattered foci of cells undergoing swelling and necrosis Most prominent in centrilobular region

Hepatocyte ballooning

Tangled skeins of intermediate filament (ubiquinated keratin of 8 and 18) Visible eosinophilic cytoplasmic inclusion in hepatocyte

Mallory-Denk body

Neutrophilic infiltration permeating the lobule and accumulating degenerating hepatocyte Lymph and mac un portal tract

Neiutrophil infiltration

Fatty liver disease on histology may appear | Fibrosis on perisinusoids

chicken wire fence pattern

Fibrosis(central vein sclerosis) then Space of disse outwards becoming chicken wire fence creating central-portal fibrous septa Liver becomes nodular, cirrhotic Micronodular cirrhosis Cryptogenic cirrhosis - burned out NASH

Fatty liver disease Laennec cirrhosis

Hepatic steatosis Alcoholic hepatits Fibrosis and cirrhosis

Alcoholic fatty liver disease

Ingestion of this amount of ethanol produce mild hepatic change (fatty liver) Chronic intake of this amount is norderline risk factor for severe

80g 40-80g/day

Metabolite of ethanol that induces lipid peroxidation and acetal-dehyde protein adduct for maturation disrupting cytoskeleton and membrane function

Acetaldehyde

Generated during oxidation of ethanol by microsomal ethanol oxidizing system reacting with damage membranes and protein

ROS

Major feature of alcoholic hepatitis and liver disease TNF is main effector of injury IL1, 6 and 8

Cytokine mediated inflammation

Most susceptibe region to toxic injury

Centrilobular

Major accelerator of liver disease in alcoholic

Concurrent Hepa C

In patients with metabolic syndrome, the best predictor of severe fibrosis and disease progression in NAFLD are

Type 2 DM Obesity Others: HTN, Dyslipidemia