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Pathology > Chapter 18 > Flashcards

Chapter 18 Flashcards

1
Q

What are the serum measurements for hepatocyte integrity

A

Aspartate aminotransferase (AST)

Alanine aminotransferase (ALT)

Lactate dehydrogenase (LdH0

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2
Q

What are the tests that look for biliary excretory function

A

Serum bilirubin

Ruin bilirubin

Serum bile acids

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3
Q

What are the tests that look for damage to the bile canaliculus

A

Serum alkaline phosphatase

Serum gamma-glutamic transpeptidase (GGT)

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4
Q

What are the tests that look for hepatocyte synthetic function

A

Serum albumin

Coagulation factors, PT, PTT, fibrinogen, prothrombin, factors V, VII, IX, and X

Hepatocyte metabolism: serum ammonia aminopyrine breath test (hepatic demethylation

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5
Q

Reversible changes in hepatocytes

A

Steatosis

Cholestasis

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6
Q

What is steatosis

A

Accumulation of bilirubin in the liver

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7
Q

Cholestasis

A

Accumulation of bilirubin in the liver

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8
Q

How does hepatocyte necrosis occur

A

Fluid flows into the cell, the cell swells, and ruptures (lysis) when osmotic regulation is interrupted

Bless also form to carry off intracellular stuff to the extracellular

Macrophages cluster at these sites of injury

Predominate mode of death in ischemic/hypoxic injury

Significant part of the response to oxidative stress

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9
Q

Hepatocyte apoptosis

A

Hepatocyte shrinkage, nuclear chromatin condensation(pkynosis), fragmentation (karyorrhexis) and cellular fragmentation into acidophilus apoptotic bodies

AKA

Acidophil bodies: apoptotic hepatocytes so named due to their deeply eosinophilic stain
-COUNCILMAN BODIES: YELLOW FEVER(SAME THIN, HISTORICAL TERM)

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10
Q

CONFLUENT NECROSIS INT HE LIVER

A

WIDESPREAD PARENCHYMAL LOSS; SEVERE, ZONAL LOSS OF HEPATOCYTES

MAY BEGIN AS A ZONE OF HEPATOCYTE DROPOUT AROUND THE CENTRAL VEIN

PRODUCE A SPACE FILLED WITH CELLULAR DEBRIS, MACROPHAGES, AND REMNANTS OF THE RETICULAR MESHWORK

SEEN IN ACUTE TOXIC INJURY, ISCHEMIC INJURIES OR VIRAL/AUTOIMMUNE HEPATITIS

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11
Q

Bridging necrosis in the liver

A

This zone links central veins to portal tracts or bridges portal tracts

Vascular insult leads to parenchymal extinction due to large areas of contiguous hepatocyte death

Collapse of supporting framework can occur

Cirrhosis may result

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12
Q

Regeneration in the liver

A

Mitosis replication adjacent to those that have died, even when there is significant confluent necrosis

Stem cell like: hepatocytes an replicate even in the setting of chronic injury
-stem cell replenishment is not a significant part of parenchymal repair

Severe forms of acute liver failure activates the primary intrahepatic stem cell niche (canal of hearing)
-contribution unclear

Ductal reactions : when hepatocytes in patients with chronic disease reach replication senescence and clear evidence of stem cell activation appears

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13
Q

Scar deposition in the liver

A

Principle cell type involved in scar deposition is the fat containing, myofibroblastic hepatic stellate cell

Quiescent form:stores lipid and vitamin A (fat soluble)

Injury: activated and converted to highly fibronectin myofibroblasts

  • cytokines released by Kupfer cells and lymphocytes: TGFB, MMP-2 (metaloproteinase-2), and TIMP-1 and 2 (tissue inhibitors of metalloproteinases 1 and 2).
  • contraction stimulated by endothelin1
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14
Q

Is scar deposition in liver reversible

A

If the injurious agent is eliminated

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15
Q

Fibrous septa development in the liver

A

Collapse of reticular where large swaths of hepatocytes have disappeared and stellate cells are activated

Regenerating hepatocytes become surrounded in late chronic disease leads to diffuse scarring (cirrhosis

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16
Q

Hepatic failure

A

Hepatic failure ensures when 80-90% of the functional capacity of the liver is lost
80% mortality without transplant

May be due to acute injury, chronic progressive injury, or acute on chronic injury

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17
Q

What is acute hepatic failure

A

Occurs within 26 weeks (6 months) of initial injury

Absence of preexisting liver disease

Associated with encephalopathy and coagulopathy

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18
Q

Causes of acute hepatic failure

A

-massive hepatic necrosis, a result of drugs/toxins

Acetaminophen (50% onset within one week) hepatitis A, autoimmune hepatitis

Hepatitis B
Hepatitis C, cryptogenic

Drugs/toxins, hepatitis D

Hepatitis E, esoteric causes (wilson disease, buds-chiaroscuro)

Fatty change of the microvesicular type (fatty liver of pregnancy, valproate, tetracycline, Reye’s syndrome)

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19
Q

Morphology acute hepatic failure

A

-massive hepatic necrosis leads to broad regions of parenchymal loss surrounding areas of regenerating hepatocytes

Small shrunken liver

Early scarring may occur in weeks-moths

Diffuse microvesicular steatosis: diffuse poisoning of liver cells without obvious cell death and parenchymal collapse; related to fatty liver of pregnancy or idiosyncratic reactions to toxins

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20
Q

What does a patient initially present with with acute hepatic failure

A

Nausea, vomiting, and jaundice which progresses to a life threatening encephalopathy and coagulation defects

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21
Q

Patients with acute hepatic failure and liver transaminases

A

Moderate increase

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22
Q

Why do people with acute hepatic failure gethepatomegalt

A

Hepatocyte swelling, infiltrates and edema initially
Eventually there is a shrunken liver as the parenchyma is destroyed
Decline in serum transaminases is an indication of fewer viable hepatocytes ,not recovery

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23
Q

Prognosis acute hepatic failure

A

Poor prognosis
Decrease in liver enzymes, indicating few remaining hepatocytes, confirmed with worsening jaundice, coagulopathy and encephalopathy

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24
Q

Sequelae acute hepatic failure

A

Jaundice and icterus: yellowing of skin , sclera and mucus membranes

Cholestasis: systemic retention of not only bilirubin but also other solutes eliminated in bile which increases the risk of life threatening bacterial infection

Hepatic encephalopathy: due to increased serum ammonia that ranges from subtle behavioral abnormalities to marked confusion and stupor to deep coma and death

  • rigidity and hyperreflexia
  • asterixix is a characteristic sign

Coagulopathy: impaired clotting due to lack of production of vitamin K dependent (II, VII, IX, and X) and independent clotting factors

  • easy bruising-early sign
  • can lead to intracranial bleeding->herniation->death

Disseminated intravascular coagulation-liver is responsible for removing activated coagulationfrom the circulation

Portal hypertension:intrahepatic obstruction most likely; leads to ascites and hepatic encephalopathy

Hepatorenal syndrome: form of renal failure in individuals with liver failure in whom their kidneys are morphologically and functionally normal

  • na retention , impaired free water excretion, decreased renal perfusion, and decreased glomerular infiltration rate
  • decreased renal perfusion pressure due to systemic vasodilation, activation of renal sympathectomy nervous system (afferent arteriole vasoconstriction), increased RAAS activation->decrease GFR
  • onset-hypo-nutria, elevated BUN creatinine
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25
Q

Asterixis

A

Characteristic sign of acute hepatic failure

Nonrhythmic, rapid extension flexion of the head and extremities

Seen with arms in extension and dorsiflexied wrists

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26
Q

Chronic liver failure

A

Associated with cirrhosis though not mutually exclusive

Chronic hepatitis B and C, non alcoholic fatty liver disease, alcoholic fatty liver disease

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27
Q

The ultimate cause of death in chronic liver failure is the same as in __ ___ ___

A

Acute liver failure

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28
Q

Ultimate cause of death from acute and chronic liver failure

A

Hepatic encephalopathy

Bleeding from esophageal varices

Bacterial infections

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29
Q

Cirrhosis

A

Diffuse transformation of the entire liver into regenerative parenchymal nodules surrounded by fibrous bands and variable degrees of vascular (portosystemic) shunting
No single cirrhosis, but rather multiple variable cirrhosis

Cirrhosis is no longer considered end stage liver disease because the fibrosis is potentially reversible with increasing numbers of effective treatments for cirrhosis causing conditions

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30
Q

Child Pugh classification of cirrhoissi

A

Helps monitor the decline of the patients ont he path to chronic liver failure

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31
Q

Class A (child Pugh)

A

Well compensated

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32
Q

Class B (child Pugh)

A

Partially compensated

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33
Q

Class C (child Pugh

A

Decompensated

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34
Q

What does stem cell activation in liver cirrhosis cause

A

Ductular reactions which increase with advancing stage of disease and are usually most prominent in cirrhoisis

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35
Q

Portal HTN cirrhosis decreased incidence morphology

A

Biopsy specimens with narrow, densely compacted fibrous septa separated by areas of intact hepatic parenchyma

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36
Q

Portal HTN increased incidence with liver cirrhosis

A

Broad bands of dense scar with dilated lymphatic space, less parenchyma; more likely to progress and lead to end stage disease

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37
Q

Clinical signs of cirrhosis before it becomes end stage

A

Only seen in 40% of patients
Jaundice+pruritis
Hypoalbuminemia->systemic edema
Hyperammonemia
Factor hepaticus:mercaptan formation
Males hyper-estrogenemia due to impaired metabolism can lead to palmar erythema, spider angiopathy, hypogonadism, and gynecomastia
Increased risk of developing hepatocellular carcinoma

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38
Q

Prehepatic causes of portal HTN

A

Obstructive thrombosis

Narrowing of the portal vein before entering the liver

Massive splenomegaly with increased splenic blood flow

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39
Q

Posthepatic causes of portal HTN

A

Severe right heart failure

Constrictive pericarditis

Hepatic vein outflow obstruction

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40
Q

Intrahepatic causes portal HTN

A

Usually due to cirrhosis
Schistomiasis
Massive fatty change
Diffuse fibrosis granulomatous disease such as sarcoidosis
Diseases effecting the portal microcirculation such as nodular regenerative hyperplasia

Increased resistance to portal flow
Increased portal venous flow due to hyper dynamic circulation

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41
Q

What is the most common cause of portal HTN

A

Cirrhosis

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42
Q

What causes increased resistance to portal flow

A

Contraction of vascular smooth muscle and myofibroblasts
Decreased NO production
Increased endothelin1, angiotensinogen, eicosanoids production
Disruption of blood flow by scarring and formation and parenchymal nodules
Remodeling and anastomoses impose arterial pressure on a normally low pressure system
Interferes with metabolic exchange of sinusoidal blood and hepatocytes

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43
Q

What causes increased portal venous flow due to hyper dynamic circulation

A

Splanchnic arterial vasodilation-increased efflux into the portal venous system

Due to NO, prostacyclin and TNF

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44
Q

Clinical portal HTN

A

Ascites
Portosystemic shunt formation
Congestive splenomegaly
Hepatic encephalopathy

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45
Q

Ascites

A

Excessive fluid in the peritoneal cavity

Detectable with accumulation of 500 ml

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46
Q

85% of ascites is due to __ __

A

Cirrhosis

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47
Q

85% of ascites is due to__

A

Cirrhosis

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48
Q

What happens with long standing ascites

A

Seepage of peritoneal fluid through trans-diaphragmatic lymphatic channels—>hydro-thorax, espicially onthe RIGHT

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49
Q

Composition of ascites

A

Fluid is serous, <3mg/dl of protein (albumin)
Neutrophils: suggests infection
Blood:suggests disseminated intraabdominal cancer

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50
Q

What leads to ascites

A

Sinusoidal HTN

Precolation of hepatic lymph in peritoneal cavity

Splanchnic vasodilation

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51
Q

Mechanism of sinusoidal ascites

A

Hepatic sinusoidal HTN drives fluid into the space of disse which is drained by lymphatics

Promoted by hypoalbuminemia->peripheral edema

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52
Q

What is the space of disse

A

Beneath the endothelial cells

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53
Q

What is found in the space of disse

A

Fat containing myofibroblastic hepatic stellate cells are found in the space of disse

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54
Q

Mechanism of ascites: percolation of hepatic lymph in peritoneal cavity

A

Normal flow is 800-1000ml; increased to 20L

The thoracic duct isn’t ably to keep up and fluid leaks out->peripheral interstitial edema

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55
Q

Mechanism of ascites: splanchnic vasodilation

A

Causes systemic hypotension which leads to vasoconstriction
RAAS activation leads to Na retention (and H2O follows)
Increased perfusion pressure of the interstitial capillaries
-transudation(protein poor) into the abdominal cavity

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56
Q

Portosystemic shunts

A

Flow is reversed from the portal into the systemic circulation where there are shared capillary bed

Esophageal varices: 40% of patients with advanced cirrhosis; rupture can cause massive hematemesis with 30% mortality

Falciform ligament and caput Medusa: dilated subcutaneous veins extend from umbilicus to rib margins

Rectum: hemorrhoids

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57
Q

Splenomegaly

A

Due to long standing congestion
Can cause thrombocytopenia(or pancytopenia

Due to long standing congestion

Can cause thrombocytopenia (or pancytopenia due to hypersplenism)

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58
Q

Hepatopulmonary syndrome

A

Hypoxia+dyspnea due to Ventillation/perfusion (V/Q) mismatch from rapid blood through dilated vessels with decreased time for diffusion

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59
Q

What exacerbates hepatopulmonary syndrome

A

Upright position due to gravity

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60
Q

What improves hepatopulmonary syndrome

A

Recumbent position

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61
Q

PortopulmonaryHTN

A

Dyspnea on excretion and clubbing

Pulmonary arterial HTN in liver disease and portal HTN

Excessive pulmonary vasoconstriction and vascular remodeling with concomitant portal hypertension

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62
Q

Acute on chronic liver failure

A

Individuals with stable, well-compensated chronic liver disease develop sudden signs of acute liver failure

Commonly have established cirrhosis and extensive vascular shunting

Significant amounts of parenchyma have borderline vascular supply and are vulnerable to superimposed insult

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63
Q

Short term mortality of acute on liver failure

A

50%

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64
Q

Hepatic A virus

A

Benign, self limited disease

Does not cause chronic hepatitis or a carrier state

Rarely lethal

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65
Q

Transmission hepatitis A

A

Fecal oral via contaminated water

Raw or steamed shellfish that get it from human sewage contaminated seawater

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66
Q

Donated blood atrisk for HAV

A

No rare

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67
Q

What kind of virus is HAV

A

Single stranded + RNA

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68
Q

Anti-HAV immunoglobulin Ig_ are seen in the serum with onset of HAV—implies acute infection

A

M

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69
Q

In HAV infection as Ig_ declines, Ig_ appears implying memory

A

M G

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70
Q

After HAV infection Ig_ persistence for years conferring long term immunity

A

G

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71
Q

Clinical HAV

A

Mild or asymptomatic and rare after childhood

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72
Q

Hepatitis B

A

Infection that has a predilection for the liver and can cause a wide spectrum of disease manifestations , with most of the cases leading to asymptomatic chronic disease or clearance

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73
Q

5 different forms of HBV induced illness

A

Acute hepatitis with recovery and clearance of virus

Non-progressive chronic hepatitis

Progressive chronic disease ending in cirrhosis

Acute hepatic failure with massive liver necrosis

Asymptomatic, ‘healthy’ carrier state

Chronically is an important precursor for hepatocelullar carcinoma

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74
Q

Transmission hepatitis b

A

High prevalence ares (AFrica, Asia): childbirth

Intermediate prevalence: horizontal (breaks in skin/mucus membranes in children with close body contact)

Low prevalence: unprotected sex, IV drug use

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75
Q

HBV viral characteristics

A

Partially dsDNA virus
Mature virus=spherical double layered “Dane particle” with outer surfac protein+lipid envelope around an electron dense slightly hexagonal core

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76
Q

Serum markers for HBV

A

HBsAg

Anti-HBs

HBeAg, HBV-DNA and DNA polymerase

Anti-HBc

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77
Q

HBsAg

A

Appears before the symptoms, peaks during the overt disease, and lasts for about 12 weeks

*donated blood is screened for HBsAg

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78
Q

Anti-HBs Ab

A

Doesn’t rise until the disease is over, about the same time that the HBaAg goes away. The IgG form is what provides the immunity

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79
Q

Anti-HBs may persist for _, conferring protection-basis for current vaccination strategies using non infectious HBsAg

A

Life

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80
Q

HBeEg, HBV-DNA and DNA polymerase

A

All appear after HBsAg and indicate there is active viral replication

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81
Q

___ espicially can be used to track the disease and antibodies to it indicate the disease is about to wane

A

HBeAg

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82
Q

Persistent HBeAg

A

Indicator of continued viral replication, infectivity, and probably progression to chronic hepatitis

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83
Q

Anti-HBe antibodies

A

Acute infection has peaked and is on the wave

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84
Q

Anti-HBc Ab

A

Appears just before the onset of symptoms and shows up with increased aminotransferase levels (liver damage)

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85
Q

What is the best predictor of HBV chronicicity

A

Age at the time of infection

Younger age-increased probability of chonicity

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86
Q

What is the main determinant of the outcome of HBV

A

Host immune response to the virus is the main determinant of the outcome of the infection

Strong response by virus specific CD4 and CD8 interferon (IFN-y)-producing cells is associated with the resolution of acute infection

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87
Q

HBV does not cause direct hepatocyte injury-what causes injury

A

CD8 cytotoxic T cells attack infected hepatocytes

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88
Q

Complete cure of HBV

A

Difficult due to viral insertion into host DNA
Limits the development of an effective immune response

Virus persists in the face of rugs that impair its replication

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89
Q

Goal of treatment in chronic HBV

A

Slow progression of disease, reduce liver damage and prevent cirrhosis and cancer

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90
Q

How do we prevent spread of HBV

A

Vaccination and screening of blood donations prevents it

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91
Q

Treat HBV

A

Most cases are self limited and resolve without treatment

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92
Q

What percent of HBV patients Barbour chronic disease

A

5-10%

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93
Q

Is fulminant hepatitis common

A

No rare

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94
Q

Morphology HBV*

A

In chronic HBV, liver biopsy shows finely granular ground glass hepatocytes packed with HBsAg
-cells with endoplasmic reticulum swollen by HBsAg-diagnostic hallmark

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95
Q

What is the diagnostic hallmark of HBV

A

Liver biopsy shows finely granular ground glass hepatocytes packed with HBsAg
-cells with endoplasmic reticulum swollen by HBsAg

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96
Q

Hepatitis C virus characteristics

A

SsRNA virus
Genomic instability+antigenic variability=no vaccine

Anti-HCV igG antibodies do not confer effective immunity and re infection is possible

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97
Q

Infection and clearance HCV

A

More mild than HBV with most acute cases being asymptomatic, but 80-90% of patients develop chronic infection and 20% get cirrhosis

Exists as closely related genetic variants inside infected patients

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98
Q

Clinical HCV

A

Characteristic repeated bouts of hepatic damage

Persistent infection and chronic hepatitis=hallmarks of HCV infection

Acute illness is generally asymptomatic chronic HCV infection==persistent elevations in serum aminotransferases
-wax and wane, but never normal

Cryoglobulinemia is found in 35% of individuals with chronic hepatitis C infection

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99
Q

Diagnose HCV

A

HCV RNA is detected in blood for 13 weeks during active infection with concurrent increase in aminotransferase levels (will see the increase in ALT/AST chronically)

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100
Q

What is HCV associated with

A 
Metabolic syndrome (genotype3)
Can give rise toinsulin resistance and non alcoholic fatty liver disease
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101
Q

Treatment HCV

A

Genotype 2 and 3 have best response to treatment, espicially in patients with IL-28B gene (encodes IFN-y involved in resistance to HCV) polymorphisms
-better response to IFN-a and ribavirin

Newer regimens may improve prognosis

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102
Q

Morphology HCV

A

Leads to portal lymphoid follicle, bile duct reactive changes and lobular regions of microvesicular steatosis

Bile duct injury is possible that can histologically mimic primary biliary cirrhosis (easily distinguished clinically)

Chronic HCV shows lymphoid aggregates or fully formed lymphoid follicles; fatty change of scattered hepatocytes

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103
Q

Hepatitis D is dependent for its life cycle on _

A

HBV

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104
Q

How is HDV dependent on HBV

A

External coat antigen surrounds an internal “delta antigen” the only protein produced by the virus

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105
Q

A vaccine for HBV also prevents __

A

HDV

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106
Q

What are the setting of HDV

A

Co-infection

Superinfection

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107
Q

How get confection HDV

A

HBV must become established first to provide the HBsAg necessary for development of complete HDV virions, resulting in acute hepatitis indistinguishable from acute hepatitis of HBV-only etiology

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108
Q

Prognosis HDV confection

A

Self limited

Followed by clearance of both viruses

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109
Q

When is there a higher rate of acute hepatitis failure with HDV coingection

A

In IV drug users

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110
Q

How detect coinfection with HDV

A

Best indicated by detection of IgM against both HDAg and HBcAg

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111
Q

Superinfection HDV

A

When a chronic carrier of HBV is exposed to a new inoculum of HDV get superinfection 30-50 days later

Severe acute hepatitis in a previously unrecognized HBV carrier, or exacerbation of pre existing chronic hepatitis B infection

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112
Q

Acute phase superinfection HDV

A

Active HDV replication and suppression of HBV with high transaminase levels

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113
Q

Chronic phase superinfection HDV

A

HDV replication decreases , HBV replication increases, transferase levels fluctuate, and disease progresses to cirrhosis and sometimes hepatocellular carcinoma

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114
Q

Lab values superinfection HDV

A

HBsAg present in serum, anti HDV persist for months or longer

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115
Q

Who gets HDV

A

Western countries: largely restricted to IV drug users and those who have had multiple blood transfusions

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116
Q

Clinical HDV

A

HDV RNA is detectable in the blood and liver just before and in the early days of acute symptomatic disease

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117
Q

Ig_ anti-HDV is the msot reliable indicator of a recent HDV exposure

A

M

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118
Q

How get HEV

A

Enterically transmitter, water borne infection

Zoonotic=animal resivoirs(increased risk with exposure to monkeys, cats, pigs, and dogs)

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119
Q

Who gets HEV

A

Occurs primarily in young to middle aged adults

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120
Q

HEV causes 30-60% of sporadic acute hepatis in ___(more than HAV)

A

India

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121
Q

Characteristic feature HEV

A

Higher mortality rate among pregnant women-almost 20%

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122
Q

Treat HEV

A

Self limiting

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123
Q

What is HEV not associated with

A

Chronic liver disease or persistent fire is in immunocompentent patients

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124
Q

In HEV virions are shed in __ during the acute illness

A

Stool

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125
Q

What type of virus i HAV

A

SsRNA

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126
Q

What type of virus is HBV

A

Partially dsDBA

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127
Q

What kind of virus is HCV

A

SsRNA

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128
Q

What type of virus in HDV

A

Circular defective SsRNA

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129
Q

What type of virus is HEV

A

SsRNA

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130
Q

What family is HAV in

A

Hepatovirus (picornavirus)

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131
Q

What family is HBV in

A

HepaDNAvirus

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132
Q

What family is HCV

A

Flaviviridae

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133
Q

What family is HDV

A

Subviral particle in deltavirdae family

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134
Q

What family is HEV

A

Hepevirus

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135
Q

Transmission HAV

A

Fecal-oral (contaminated H2O)

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136
Q

Transmission HBV

A

Parenteral, sexual contact, perinatal

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137
Q

What family is HCV

A

Parenteral, intranasal cocaine

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138
Q

Family HDV

A

Parenteral

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139
Q

Family HEV

A

Fecal oral

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140
Q

Incubation HAV

A

2-6 weeks

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141
Q

HBV incubation

A

2-26 weeks (avg 8)

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142
Q

HCV incubation

A

4-26 weeks (avg9)

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143
Q

HDV incubation

A

2-26 weeks (avg 8)

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144
Q

HEV incubation

A

4-5 weeks

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145
Q

HAV progression to chronic

A

Never

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146
Q

HBV progression to chronic

A

5-10%

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147
Q

HCV progression to chronic

A

> 80%

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148
Q

HDV progression to chronic

A

10% coinfection

90-100% superinfection

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149
Q

HEV progression to chronic

A

Never

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150
Q

Diagnosis HAV

A

IgM antibodies

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151
Q

HBV diagnosis

A

HBsAg, antiHBcAg; PCR for DNA

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152
Q

HCV diagnosis

A

PCR for DNA, Elisa for Ab

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153
Q

HDV diagnosis

A

IgM and IgG antibodies; HDV RNA serum; HDAg in liver

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154
Q

Diagnosis HEV

A

Serum IgM and IgG; PCR for HEV RNA

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155
Q

Which hepatitis show fulminant

A

A, B, D

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156
Q

Which hepatitis fulminant in pregnant women

A

HEV

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157
Q

Clinicopathological syndromes of hepatitis

A

Acute asymptomatic infection with recovery (serologic evidence only)

Acute symptomatic hepatitis with recovery (anicteric or interic)

Chronic hepatitis

Acute liver failure

Carrier state

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158
Q

Acute asymptomatic infection with recovery (serologic evidence only)

A

Worldwide, HAV, and HBV infections are frequently subclinical events in childhood verified only in adulthood by the resented of anti-HAV or anti HBV antibodies

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159
Q

Acute symptomatic hepatitis with recovery (anicteric or icteris) four phases

A

Incubation(peak infectivity during last asymptomatic days of incubation period and early days of acute symptoms)

Symptomatic pre-icteric phase

Symptomatic interic phase

Convalescence

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160
Q

Chronic hepatitis

A

With progression to cirrhosis

Without progression to cirrhosis

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161
Q

Acute liver failure

A

With massive hepatic necrosis

With submissive hepatic necrosis

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162
Q

Carrier state hepatitis

A

“Healthy carrier’: individual with HBsAg, no HBeAg, andi HBeAg, normal aminotransferases low or undetectable serum HBV DNA, and liver biopsy showing a lack of significant infalmmation and necrosis

Inactive carrier
Not recognized in the United States

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163
Q

Acute hepatitis morphology

A

Lymphoplasmactyic (mononuclear) infiltrate

Spotty necrosis or lobular hepatitis scattered throughout a lobule

Necrosis empty cytoplasm , cell membrane ruptures leads to hepatocyte dropout

Collapsed sinusoidal collagen reticulin framework

Apoptosis; hepatocytes shrink, become eosinophilic, pyknotic, fragmented

Lack of portal inflammation

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164
Q

Severe acute hepatitis morphology

A

CONFLUENT NECROSIS of hepatocytes around central veins

Cellular debris, collapsed reticulin fibers, congestion +/- hemorrhage

Variable inflammation

Central portal BRIDGING NECROSIS leads to parenchymal collapse

Can lead to massive hepatic necrosis/acute failure

Can develop post hepatitis. Cirrhosis with abundant scarring

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165
Q

Chronic hepatitis morphology

A

Mononuclear portal infiltration

Mild: inflammatory infiltrates are limited to portal tracts

Progressive dise: extension of chronic inflammation from portal tracts with interface hepatitis

Linking of orca and portal central regions=bridging necrosis

Continued loss of hepatocytes=fibrous septum formation

Associated hepatocyte regeneration=cirrhosis

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166
Q

What causes toxic shock syndrome

A

Staphylococcus aureus

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167
Q

What causes typhoid fever

A

Salmonella typhi

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168
Q

What causes secondary or tertiary syphilis

A

Treponema pallidum

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169
Q

Ascending cholangitis

A

Acute infalammation response within the intrahepatic biliary tree due to intrabiliary bacterial microflora during a partial or complete obstruction

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170
Q

What is autoimmune hepatitis

A

Chronic, progressive hepatitis

Presence of autoantibodies
Therapeutic response to immunosuppression

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171
Q

What triggers autoimmune hepatitis

A

Viral infection, drug/toxin exposure

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172
Q

Patients at risk for autoimmune hepatitis

A

Caucasion: DRB1* alleles (HLA association)—genetic predisposition

Most frequent in white Northern Europeans

Females predominance

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173
Q

What are the two types of autoimmune hepatitis

A

2 types based on circulating antibodies

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174
Q

Type 1 autoimmune hepatitis

A

Middle aged older people

ANA (anti-nuclear), ASMA (anti-smooth msucle), ANTI-SLA/LP (anti-soluble liver antigen/liver-pancreas antigen), AMA (anti-mitochondrial) antibodies

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175
Q

Type 2 autoimmune hepatitis

A

Children and teenagers

Anti-LKM1 (anti-liver kidney microsome-1) antibodies against CYP2D6

ACL1 (anti-liver cytosolic) antibodies

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176
Q

Early phase of severe parenchymal destruction followed rapidly by scarring

A

-fibrosis take years to develop in chronic viral hepatitis, does not develop in acute hepatitis

Severe necroinfalmmatory activity indicated by interface hepatitis or parenchymal collapse

Mononuclear infiltrate: plasma cells

Hepatocyte ROSETTES in areas of activity

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177
Q

Early phase autoimmune hepatitis

A

Severe parenchymal destruction followed rapidly by scarring

Fibrosis takes years to develop in chronic viral hepatitis, does not develop in acutehepatitis

Severe necroinflammatory activity indicated by interface hepatitis or parenchymal collapse

Mononuclear infiltrate: plasma cells

Hepatocyte ROSETTES in areas of activity

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178
Q

Progressive or indolent automimmune hepatitis that lead to liver failure initial and chronic siding

A

Initial: severe hepatocyte injury with necrosis but little scarring
Chronic: burned out cirrhosis with little necroinflammatory activity; likely due to years of subclinical disease

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179
Q

With autoimmune hepatitis, acute onset with fulminant disease in _ weeks

A

8

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180
Q

Autoimmune hepatitis hepatic encephalopathy

A

Yup

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181
Q

What happens if autoimmune hepatitis is untreated

A

40% mortality in 6 months

Both type 1 and type 2 are likely to lead to liver failure

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182
Q

What percent of autoimmune hepatitis survivors have cirrhosisi

A

40%

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183
Q

Characteristic autoimmune hepatitis

A

Plasma cells are prominent and characteristic component of the inflammatory infiltrate in biopsy specimens showing autoimmune hepatitis

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184
Q

Prognosis autoimmune hepatitis

A

Between in adults than in children (delay in diagnosis in pediatric population)

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185
Q

Treat autoimmune hepatitis

A

80% of patients respond to immunosuppression for long term survival

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186
Q

End stage autoimmune hepatitis

A

Liver transplant with 75% survival at 10 years, recurrent ein 20% of patients

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187
Q

Drug or toxin liver damage

A

May be immediate or delayed
Mild to severe

Predictable (intrinsic, dose dependent) or unpredictable (idiosyncratic, multi-factorial)

Due to direct toxicity, conversion of a xenobiotic to a toxin or from immune mediated toxicity

Recovery usually occurs with removal of the offending agent

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188
Q

What is the most common cause of acute liver failure necessitating liver transplant in the USA

A

Acetaminophen

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189
Q

Why does acetaminophen cause liver failure

A

Due to toxic metabolite produced from the CYP450 breakdown in acinus zone 3 hepatocytes

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190
Q

What is zone 3

A

Closest to the terminal hepatic vein (central vein) and furthest from the portal vein

Central vein turns into the hepatic vein

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191
Q

Zone 2

A

Tries to compensate and become injured

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192
Q

Severe acetaminophen overdose

A

The zone of injury extends into zone 1 (periportal hepatocytes) and this is when you start getting acute hepatic failure

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193
Q

Why can alcohol or codeine make acetaminophen

A

Upregulate CYP450 and make things worse

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194
Q

Chlorpromazine and liver

A

Cholestasis in patients who are slow to metabolize it to an innocuous byproduct

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195
Q

Halothane and liver

A

Fatal immune mediated hepatitis in some patents exposed on multiple occasions

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196
Q

What are the types of liver disease caused by alcohol

A

Hepatocellular steatosis or fatty change

Alcoholic hepatitis

Streatofibrosis up to and including cirrhosis (only in a small fraction)

  • patterns of scarring typical for all fatty liver diseases including alcohol
  • cirrhosis develops in only a small fraction of chronic alcoholics
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197
Q

Hepatic steatosis (fatty liver)

A

Microvesicular lipid droplets within hepatocytes

With chronic use accumulates in microvesicular droplets which displace the nucleus

Large, soft, greasy, yellow liver

No fibrosis

Completely reversible if patients abstains from alcohol

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198
Q

Alcoholic (steato-) hepatitis

A

Hepatocyte swelling (fat, H2O, proteins)+necrosis

Mallory-denk bodies

Neutrophilic reaction to degenerating hepatocytes, espicially those with Mallory dunk bodies

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199
Q

Mallory desk bodies

A

Intracellular eosinophilic aggregates of intermediate filaments (keratin 8 and 18, ubiquitin) in ballooning hepatocytes
-hepatocytes are epithelial cells
Mallory desk bodies==damaged intermediate filaments(in hepatocytes, cytokeratin)

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200
Q

What are Mallory denk bodies seen in

A

Alcoholic hepatitis, non alcoholic fatty liver disease, wilson disease, and chronic biliary tract disease

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201
Q

Mallory denk bodies mean alcoholic hepatitis

A

Characteristic finding in alcoholic hepatitis but not specific

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202
Q

Alcoholic steatofibrosis

A

Activation of sinusoidal stellate cells+portal fibroblasts=fibrosis (fibrosis begins with sclerosis of central veins (zone3)

Scarring in a chicken wire fence pattern

Laennec cirrhosis with continuous use due to developing modularity and progressive inter webbing of the scare

Liver is large, brown, shrunken and non fatty

Closer to cirrhosis =less likely to regress

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203
Q

Alcoholic steatlfibrosis scarring in chicken wore fence pattern

A

Fibrosis spreads outward and encircles individual or small clusters of hepatocytes

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204
Q

Acloholic steatofibrosis laennec cirrhosis with continuous use due to developing modularity and progressive inter-webbing of the scares

A

Classic micro nodular cirrhosis first described for end stage alcoholic liver disease

Cirrhosis==chronic liver disease; laennec (aka micro nodular)==chicken-wire==alcoholic steatofibrosis

Large bands of fibrous tissue surrounding nodules

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205
Q

Risk factors for developing alcoholic cirrhosis

A

10-115% of alcoholics develop cirrhosis

Females are more susceptible

African American>caucasion

Iron overload, HBV, HCV=increased severity of liver disease

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206
Q

Mutation for alcohol intolerance

A

Homozygous ALDH*2 (asians) has alcohol intolerance

Flushing, nausea, lethargy

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207
Q

Hepatocellular steatosis pathogenesis

A

Impaired lipoprotein assembly and secretion

Increased peripheral catabolism of fat-> release of free fatty acids into the circulation

Shunting of substrates away from catabolism and towards lipid biosynthesis (due to increased NADH production by enzymes of metabolism)
-alcohol dehydrogenase and acetaldehyde dehydrogenase-> increased NADH production

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208
Q

Alcoholic hepatitis pathogenesis

A

Acetylaldehyde induced lipid peroxidation and protein adduct formation (carcinogen)

Induced CYP450-increases conversion of other agents to form potentially toxic metabolites

Impaired methionine metabolism

Release of bacterial endotoxin (LPS)

Release of endothelin1

Decreased perfusion of hepatic sinusoids

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209
Q

Effect of impaired methionine metabolism

A

Decreases glutathione levels that are normally protective of ROS

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210
Q

What happens when alcohol causes the release of bacterial endotoxin (LPS)

A

Pro inflammatory

Estrogen increases gut permeability to endotoxin (LPS)->increased expression of the LPS receptor (CD14, TLR4) in kupffer cells==women are more sensitized to pro inflammatory effects

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211
Q

Alcoholic liver disease pathogenesis

A

Chronic disorder of steatosis, hepatitis, progressive fibrosis and deranged perfusion

Due to an agent that was initially only marginally harmful

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212
Q

Clinic hepatic steatosis

A

Hepatomegaly

Mild increase of serum bilirubin and alkaline phosphatase levels

Severe dysfunction Is rare

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213
Q

Alcoholic liver disease clinical

A

AST:ALT>2:1

90% 5 year survival with abstinence in patients free of jaundice, ascites, or hematemesis

50-60% 5 year survival in patients that do not discontinue use

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214
Q

Alcoholic hepatitis clinical

A

Increased bilirubin, alkaline phosphatase and aserum aminotransferase

Neutrophilic leukocytosis

Nonspecific symptoms: malaise, anorexia, weight loss, abdominal discomfort

Follows a bout of heavy drinking

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215
Q

Treatment alcoholic hepatitis

A

Cessation of alcohol+adequate nutrition may slowly clear disease

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216
Q

Each bout of alcoholic hepatitis has a _% risk of death

A

10-20

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217
Q

If a patient with alcoholic hepatitis refrains from alcohol can they still progress to cirrhosis

A

Yup

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218
Q

_% of people with alcoholic hepatitis progress to cirrhosis without treatment

A

1/3

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219
Q

Clinical alcoholic cirrhosis

A

Hepatic dysfunction: increased aminotransferase, bilirubin, alkaline phosphatase, hyperproteinemia (globulins, albumin, clotting factors)

Anemia

May be clinically silent

Generally irreversible

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220
Q

End stage alcoholic hepatitis

A

Hepatic coma

Massive GI hemorrhage

Intercurrent infection(predisposed to infection)

Hepatorenal syndrome after bout with hepatitis

Hepatocellular carcinoma

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221
Q

What is the most common cause of chronic liver disease in the USA

A

Non alcoholic fatty liver disease

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222
Q

Non alcoholic fatty liver disease

A

Spectrum of disorders with hepatic steatosis

Patients consume<20g alcohol/week

80gm/day of alcohol is considered the threshold for the development of alcoholic liver disease

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223
Q

Risk factors for non alcoholic fatty liver disease

A

Increased incidence due to increased obesity and the association with metabolic syndrome

Contributes to progression of other liver disease (HBV, HCV)

Increased risk of hepatocellular carcinoma

Hispanic>african American>caucasion

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224
Q

Two hit model of non alcoholic fatty liver disease

A

Insulin resistance leads to hepatic steatosis

Hepatocellular oxidative injury leads to liver cell necrosis and inflammatory reactions

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225
Q

What factors can lead to hepatic steatosis, obesity, and insulin resistance

A

Increased high calorie food intake, high fructose corn syrup, decreased exercise, genetic predisposition

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226
Q

How does metabolic syndrome lead to nonalcoholic fatty liver disease

A

Dysfunctional adipose tissue (endocrine organ), decreased production of adiponectin, increased TNFa, IL6=hepatocyte apopotosis

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227
Q

Why get apoptosis with non alcoholic fatty liver disease

A

Oxidative damage to mitochondria and plasma membranes

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228
Q

Mitochondria and non alcoholic fatty liver disease

A

Oxidative damage

Further damaged by decreased autophagy and formation of mallory denk bodies

229
Q

Scar tissue non alcoholic fatty liver disease

A

Scar tissue deposition due to kupffer cells, TNF-a, TGF-b which activates stellate cells (which are also activated through the hedgehog signalling pathway

230
Q

Level of __ __ activity correlated with the stage of fibrosis in non alcoholic fatty liver disease

A

Hedgehog pathway

231
Q

Morphology non alcoholic liver disease

A

Pathological steatosis=involvement of >5% of hepatocytes

Overlaps with histology of alcoholic hepatitis, but

  • mononuclear cells more prominent
  • portal fibrosis more prominent
  • mallory denk less common

90% of cryptogenic cirrhosis is not considered “burned out” non alcoholic fatty liver disease

232
Q

Morphology children non alcoholic fatty liver disease

A

Diffuse steatosis and portal fibrosis

Portal+parenchymal infiltrate parenchymal neutrophils

233
Q

Clinical non alcoholic fatty liver disease

A

Usually asymptomatic or have nonspecific symptoms with RUQ pain

Increase AST, ALT—liver dysfunction

D

234
Q

Diagnosis non alcoholic fatty liver disease

A

Liver biopsy

235
Q

Most common cause of death with non alcoholic fatty liver disease

A

Cardiovascular death

236
Q

What is non alcoholic fatty liver disease associated with

A

Obesity and diabetes

237
Q

What will liver biopsy show non alcoholic fatty liver disease

A

Pattern will be microvesicular steatosis, with large lipid vacuoles filling hepatocytes

238
Q

Treat non alcoholic fatty liver disease

A

Correct obesity, hyperlipidemia, insulin resistance

-address the underlying metabolic syndrome

239
Q

WHO criteria for diagnosis of the metabolic syndrome

A

One of: diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, or insulin resistance

Two of: BP>140/90
TG>1.695 and HDL.9 (male) >.85 (female) or BMI>30

Microalbuminuria: urinary albumin excretion>20 or albumin: Cr>30

240
Q

Hemochromatosis

A

Excessive iron absorption deposited in parenchymal organs such as the liver and pancreas followed by heart, joints, and endocrine organs

241
Q

How get hemochromatosis

A

Hereditary or due to excessive intake (secondary)

242
Q

Hereditary hemochromatosis

A

Slow progression with symptoms appearing in 4th-5th decades for males, later (if ever) for females due to menstruation until menopause

  • iron accumulation is lifelong
  • injury caused be excess iron is slow and progressive
243
Q

Secondary (acquired) hemochromatosis

A

Most common cause is associated with ineffective erythropoiesis (severe thalassemia and myelodysplastic syndrome)-excessive iron from transfusion+increased absorption

Transfusions, when given repeatedly over a period of years (ie. patients with chronic hemolytic anemia)->systemic hemosiderosis and parenchymal organ injury

Chronic liver disease->loss of hepatocyte mass->impaired hepcdin production_>increased iron uptake from the gut->iron overload

244
Q

Fully developed , severe hemochromatosis

A

Micronodular cirrhsosis in all patients

Diabetes mellitus in 75-80%

Abnormal skin pigmentation in 75-80%

245
Q

Hereditary hemochromatosis cause

A

Mutation in the HFE gene, whose product is involved in intestinal iron uptake by its effects on hepcidin levels

246
Q

What do we se with hereditary hemochromatosis

A

Intestinal absorption of dietary iron is abnormal

Net accumulation of .5-1g/yearmanifests with accumulation 20g

One of the msot comon genetic disorders in humans

247
Q

Iron toxicity hemochromatosis

A

Lipid peroxidation cia iron-catalyze ROS

Stimulation of collagen formation by activation of hepatic stellate cells

Interaction of ROS and Fe itself with DNA leads to lethal cell injury and predisposition to hepatocellular carcinoma

248
Q

Is iron toxicity in hemochromatosis reversible

A

If cells not fatally injured

249
Q

How treat iron toxicity hematochromatosis

A

Removal of excess iron promotes recovery of function

250
Q

Hepcidin

A

Main regulator of iron absorption

251
Q

Action of hepcidin

A

Lowers plasma iron levels

252
Q

Hepcidin binds __ and internalized the transport channel, preventing iron from leaving intestinal cells and macrophages

A

Ferroportin

253
Q

Transcription of hepcidin is increased by:

A

Inflammatory cytokines and iron

254
Q

Transcription of hepcidin is deacreased by :

A

Iron defiency, hypoxia, and ineffective erythropoiesis

255
Q

Deficient hepcidin

A

Iron overload

256
Q

Mutations in hepcidin

A

Hemochromatosis

257
Q

What is the most common cause of adult hemochromatosis

A

HFE mutation(C282Y>H63D)

Chromosome 6, near an HLA locus

258
Q

What does HFE mutation of hepcidin cause

A

Adult form of hemochromatosis

259
Q

What does HFE mutation C282Y cause

A

Inactivation of HEF->inactivation/defiency of hepcidin->hemochromatosis

260
Q

Who gets C282Y

A

White population

261
Q

Penetrance C282Y

A

Low penetrance

262
Q

H63D hepcidinmutation(less common than C282Y) who gets it

A

Worldwide distribution

263
Q

TFR@ hepcidin mutation

A

Less common

264
Q

Hepcidin mutation HJV or HAMP

A

Juvenile hemochromatosis

-more severe form of the disease than the adult variety

265
Q

Hemochromatosis liver

A

Deposition of hemosiderin in liver, seen with Prussian blue stain

Golden yellow hemosiderin granules initially form, and fibrous septa slowly develop

Leads to small, shrunken liver micronodular cirrhosis

Iron is directly hepatotoxic and there is no inflammation
Late stages the liver is dark brown black due to iron accumulation

266
Q

Hemochromatosis pancreas

A

Deposition of hemosiderin, seen with Prussian blue stain

Intensely pigmented

Diffuse interstitial fibrosis

Parenchymal atrophy

Hemosiderin in islet and acinar cells

267
Q

Hemochromatosis heart

A

Enlarger with hemosiderin granules in myocardial fibers-> striking brown coloration

Delicate interstitial fibrosis

268
Q

Hemochromatosis skin

A

Pigmentation due to increased melanin production causing a gray slate color

Some due to hemosiderin deposition in dermal macrophages and fibroblasts

Mechanism is unknown

269
Q

Hemochromatosis acute synovitis

A

Leads to pseudo gout from calcium pyrophosphate deposition

270
Q

Hemochromatosis testes

A

Small, atrophic testes due to hypothalamic pituitary axis disruption and decreased hormone production

271
Q

Clinical tetras hemochromatosis

A

Hepatomegaly, abnormal skin pigmentation (espicially in sub exposed areas), deranged glucose homeostasis or DM due to destruction of pancreatic islet cells and cardiac dysfunction (arrhythmia, cardiomyopathy)

Atypical arthritis
Hypogonadism

272
Q

Who gets hemochromatosis

A

Males over 40

273
Q

What do people with hemochromatosis have high risk for

A

200x increased risk of hepatocellular carcinoma

274
Q

Does treatment of iron overload in hemochromatosis remove risk of cancer

A

Not fully bc DNA alterations that occur prior to time of diagnosis and initiation fo treatment

275
Q

Diagnose hematochormis

A

Diagnosible long before irreversible tissue damage occurs

Look for iron in the tissues with Prussian blue
-Prussian blue stains hepatocellular iron blue

Screen for high levels of serum iron and ferritin

Screen family members

276
Q

Screening hematochromatosis

A

Diagnosis can be made before irrreversible tissue damage occurs

Screen for very high levels of serum iron and ferritin, exclusion of secondary causes or iron overload and liver biopsy if still in doubt

277
Q

Heterozygous hematochromatosis

A

Still accumulate excess iron, but not to a level that causes significant tissue damage

278
Q

Treat hematochromatosis

A

Regulat phlebotomy (blood letting) depletes tissue stores or iron=normal life expectancy

279
Q

Neonatal (congenital) hemochromatosis

A

Severe liver disease and extrahepatic hemosiderin deposition of unknown origin

280
Q

Is neonatal hemochromatosis inherited

A

No

281
Q

Why get neonatal hemochromatosis

A

Liver injury occurs in utero; may be due to materanla alloimmune injury to fetal liver

Extrahepatic hemosiderin deposition (buccal) has to be documented for proper diagnosis

282
Q

Treat for neonatal hemochromatosis

A

No treatment, supportive care and possible liver transplant

283
Q

Wilson disease mutation

A

AR disorder via ATP7B

284
Q

Wilson disease problem

A

Impaired shopper excretion into bile and failure to incorporate copper into ceruloplasmin which leads to toxic levels of copper in the liver, kidney and eye (also kidney, bones, joints)

285
Q

Pathogenesis wilson

A

Copper absorption and delivery to the liver is normal but excretion into bile is reduced, it is not incorporated into ceruloplasmin and ceruloplasmin secretion into the blood is inhibited

Copper accumulated in the liver cause injury via ROS

Non ceruloplasmin bound copper spills into circulation leads to hemolysis and pathology elsewhere

286
Q

Why does copper cause toxic liver damage

A

Promotes formation of free radicals by the Fenton reaction
Binds to sulfhydral groups of cellular proteins

Displaces other metals from hepatic metalloenzymes

287
Q

Morphology Wilson’s disease

A

Fatty change
Acute and chronic hepatitis with Mallory denk bodies
Eventually leads to cirrhosis
+/- necrosis
CNS toxicity: basal ganglia atrophy and cavitation
Kayser-fleischer rings:green brown copper deposits in descent membrane
Can use rhodamine or orcein stains to look for the copper

288
Q

In Wilson’s there is __ urinary excretion of copper and _ plasma ceruloplasmin

A

Elevated

Low

289
Q

How does wilson present

A

Acute or chronic liver disase that presents between 6-40 years

Neurological involvement: movement disorders or rigid dystonia (may be confused with parkinsonism)

290
Q

Copper toxicity(wilson) primarily impacts the __ __, espicially the ___

A

Basal ganglia

Putamen

291
Q

Huntington signs

A

Poor coordination, chorea, or choreathetosis

292
Q

Parkinson sign

A

Spastic dystonia, mask life fancies, rigidity, and gait disturbances

293
Q

Psychotic symptoms wilson

A

Land these patients in mental institutions

294
Q

Why do people with wilsons get hemolytic anemia

A

Copper toxicity to RBC membranes-elevated direct bilirubin

295
Q

Diagnosis wilson

A

Decreased serum ceruloplasmin

Increased hepatic copper content (most sensitive and accurate)

  • demonstration of hepatic copper content in excess 250 microgram/gram is most helpful
  • increased urinary copper excretion (most specific screening test)
296
Q

Treatment wilson

A

Long term chelation therapy or zinc based therapy

Liver transplant if unmanageable cirrhosis develops;this is curative

297
Q

A1 antitrypsin defiency (a1AT defiency)

A

AR disorder of protein folding

298
Q

PiMM a1AT

A

Wild type 90% of people

299
Q

PiZz a1AT

A

Most common clinically relevant genotype

300
Q

PiZz homos

A

10% of the normal circulating a1-antitrypsin level

301
Q

How does PiZz present

A

Very early with liver disease-a1 antitrypsin defiency is the most commonly diagnosed inherited hepatic disorder in infants and children

302
Q

A1AT have _ serum a1-antitrypsin

A

Low

303
Q

What does a1-antitrypsin do

A

Inhibit proteases (neutrophil elastase, cathepsin G, and proteinase 3)

304
Q

What does a1AT defiency lead to

A

Pulmonary emphysema because activity of destructive proteases is not inhibited

Hepatic disease(cholestasis or cirrhosis) because of hepatocellular accumulation of the misfolded protein->ER stress->ER stress (misfolded protein) response->apoptosis

305
Q

A1AT defiency is the most commonly diagnosed inherited hepatic disorder of _ and _

A

Infants and children

306
Q

Pathogenesis a1AT defiency

A

Mutation prevents migration of the protein from the ER to the golgi, leading to accumulation of the protein in the liver

All patients with PiZz genotype accumulate protein but only10-25% develop liver disease

307
Q

Morphology a1AT defiency

A

Characterized by presence of round to oval cytoplasmic globular inclusions in periportal hepatocytes (*****acidophilic, PAS(+) following diastase digestion of the liver

Number of globules does not represent severity of disease
Ranges from cholestasis to hepatitis to cirrhosis

308
Q

Clinical a1AT defiency

A

Neonatal hepatitis+cholestasis jaundice in 10-20% of affected newborns

Adolescence:present with hepatitis , cirrhosis or pulmonary disease (may regres and recur)

May be silent until later in life

Hepatocellular carcinoma in 2-3% of PiZz adults

309
Q

Treat a1AT defiency

A

Orthotopic liver transplant (cure)

In patients with pulmonary disease, the single most preventative measure is avoidance of cigarette smoking

310
Q

Function of bile

A

Emulsification of dietary fat in the lumen of the gut through the detergent action of bile salts

The elimination of bilirubin, excess cholesterol, xenobiotics, and other waste products that are insufficiently water soluble to be excreted into urine

311
Q

Most of the bilirubin in the serum is what

A

Complexed onto albumin-unconjugated

312
Q

Is there any bilirubin free in the plasma

A

Super small amount

313
Q

Can album -bilirubin be excreted in urine

A

No, no matter how high the serum concentration

314
Q

A little bit os serum bilirubin-albumin is able to diffuse into tissues, espicially in what

A

Into premature infants brain(erythroblastosis fetalis leading to kernicterus)

315
Q

Normal bilirubin levels

A

.3-1.2 mg/dL

316
Q

Jaundice levels of bilirubin

A

> 2.5 mg/dL

317
Q

Neonatal jaundice

A

The ability to conjugate and excrete bilirubin doesn’t occur until about 2 weeks of age

It is normal and expected for newborns to go through transient phases of jaundice in the beginning of life

Can be exacerbated by breastfeeding due to bilirubin-deconjugate enxymes present in milk

318
Q

Crigler najjar syndrome 1

A

AR complete enzyme defiency
No UGT1A1 activity

Unconjugated hyperbilirubinemia

319
Q

Prognosis crigler najjar 1

A

Fatal in neonatal period

More severe than II

320
Q

ARcrigler najjar II

A

AD, variable penetrance
Decreased UGT1A1 activity

Unconjugated hyperbilirubinemia

321
Q

Prognosis criglerr najjar II

A

Mild clinical course with only occasional kernicterus

322
Q

Gilbert syndrome

A

AR decreased UGT1A1 activity

Innocuous

Unconjugated hyperbilirubinemia

323
Q

Dubin johnson

A

AR
Mutated MRP2
Conjugated hyperbilirubinemia

Innocuous

Impaired excretion of bilirubin glucuronides

324
Q

Signs of dubin johnson

A

Black liver
Mutated canalicular MDR protein 2

Pigmented cytoplasmic globules

Innocuous

325
Q

Rotor syndrome

A

AR

Conjugated hyperbilirubinemia

326
Q

Cholestasis

A

Impaired bile formation and flow->accumulation of bile pigment within the hepatic parenchyma

327
Q

Signs of cholestasis

A

Jaundice, pruritus, skin xanthomas, malabsorption, vitamin ADEK deficiencies

328
Q

Labs cholestasis

A

Characteristic elevated serum y-glutamyl transpeptidase (GGT) and alkaline phosphatase

ALT and AST are normal as they indicate there has been loss of hepatocytes integrity

329
Q

In cholestasis there is accumulation of bile pigment in the __ __ and longated green-brown plugs of bile are found in dilated bile canaliculi

A

Hepatic parenchyma

330
Q

What are feathery degeneration of periportal hepatocyte (zone 1) incholestasis

A

Droplets of bile pigment that can be found in hepatocytes with a fine, foamy appearance

331
Q

In in cholestasis there are __ ammlry denk bodies

A

Periportal

332
Q

What are some common causes of large bile duct obstruction in adults

A

Extrahepatic cholelithiasis, malignancies of the biliary tree or head of the pancreas, strictures resulting from previous surgical procedures

333
Q

Large bile duct obstruction commmon causes in kids

A

Biliary atresia, cystic fibrosis,choledochal cysts, and syndromes in which there are insufficient intrahepatic bile ducts

334
Q

Treat cholestasis

A

Extrahepatic bile obstruction is treatment with surgery

335
Q

Common causes of large bile duct obstruction in kids

A

Biliary atresia, cystic fibrosis, choledochal cysts, and syndromes in which there are insufficient intrahepatic bile ducts

336
Q

Ascending cholangitis

A

A secondary bacterial infection of the biliary tree that aggravates the inflammatory injury

337
Q

What causes ascending cholangitis

A

Subtotal or intermittent obstruction

338
Q

What causes ascending cholangitis

A

Enteric bugs like coliforms and enterococci

339
Q

Charcot triad of ascending cholangitis

A

Fever, RUQ pain, jaundice

Also get chills

340
Q

Histology ascending cholangitis

A

Influx of periductular neutrophils directly into the bile duct epithelial and lumen

341
Q

Ascending cholangitis may be superimposed on the chronic process so that there is acute-on-chronic __ __

A

Liver failure

342
Q

What can ascending cholangitis lead to

A

Suppurative cholangitis (most severe; risk of sepsis)

343
Q

Suppurative cholangitis

A

Purple NT bile fills and distended bile ducts

Frequently complicated by sepsis (instead of cholestasis)—sepsis is life threatening

344
Q

How can intrahepatic bacterial infection directly cause cholestasis of sepsis

A

Abscess formation, bacterial cholangitis

345
Q

How can liver cirrhosis cause cholestasis of sepsis

A

Ischemia related to hypotension caused by sepsis, espicially when liver is cirrhosis

346
Q

How can circulating microbial products cause cholestasis of sepsis

A

Most likely to lead to the cholestasis of sepsis

Most commmon form of this==canalicular cholestasis

  • bile plugs within predominantly ventriloquial canaliculi
  • associated with activation of kupffer cells and mild portal inflammation
  • hepatocyte necrosis is scant or absent
347
Q

Ductular cholestasis

A

Dilated canals of hearing and bile duct ulcers at the interface of portal tracts and parenchyma become dilated and contain obvious bile plugs

348
Q

Biliary cirrhosis

A

Due to chronic biliary obstruction and ductular reactions that lead to periportal fibrosis and eventually hepatic scarring and nodule formation

There may also be bile infarcts from the detergent effects of the extravasated bile

349
Q

Primary heptolithiasis

A

Disease of intrahepatic gallstone formation that leads to repeated bouts of ascending cholangitis, progressive inflammatory destruction of hepatic parenchyma, and predisposes to biliary neoplasia

350
Q

Where is primary hepatocyte I asis common

A

East Asia

351
Q

Morphology primary hepatolithiasis

A

Pigmented Ca bilirubinate stones in distended intrahepatic bile ducts

Ducts show chronic inflammation, mural fibrosis, and peribiliary gland hyperplasia

Biliary dysplasia may also be seen—>may evolve to invasive cholangiocarcinoma

352
Q

What do people with primary hepatolithiasis have an increased risk of getting

A

Cholangiocarcinoma by unknown mechanism

353
Q

Neonatal hepatitis

A

Liver injury/inflammation in the neonate

Leads to jaundice, dark urine, light or acholic stools, hepatomegaly

There may be varying levels of impaired hepatic synthetic function

354
Q

Neonatal cholestasis

A

Prolonged conjugated hyperbilirubinemia in the neonate after 2 weeks (not physiological jaundice of the newborn)

355
Q

Morphology neonatal hepatitis

A
  • panlobular giant-cell transformation of hepatocytes
  • lobular disarray with local liver cell apopotosis and necrosis
  • hepatocellular and canalicular cholestasis
  • mild mononuclear infiltration of the portal areas with reactive changes in kupffer cells
  • extramedullary hematopoiesis
356
Q

Biliary atresia

A

Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first three months of life

357
Q

What is the most common cause of neonatal cholestasis and death from liver disease in early childhood

A

Biliary atresia

358
Q

Pathogenesis of fetal biliary atresia

A

Associated with other anomalies resulting from ineffective establishment of laterality of thoracic and abdominal organs during development

Due to aberrant intrauterine development of the extrahepatic biliary tree

359
Q

Pathogenesis of perinatal biliary atresia

A

Most common 80%

Destruction of the normal biliary tree shortly after birth

Rotavirus, CMV, reovirus, autoimmune are all implicated

Genetic basis

360
Q

Morphology biliary atresia

A

Inflammatory and fibrosis stricture of the hepatic or common bile ducts

Progressive destruction of the intrahepatic biliary tree

361
Q

Clinical presentation biliary atresia

A

Neonatal cholestasis, but normal weight gain

Normal stools change into acholic stools

Jaundice lasts longer than 2 weeks

362
Q

Serum bilirubin in biliary atresia

A

6-12 mg/dL

363
Q

What happens if biliary atresia is left untreated

A

Leads to cirrhosis in 3-6 months after birth, death by 2

364
Q

Treatment biliary atresia

A

If limited to common duct(typeI) or left/right hepatic ducts(typeII):Kauai procedure

Obstruction above the porta hepatitis(typeIII): not correctable (90%) and needs liver transplant
-no patent bile ducts amendable to surgical anastomsis

365
Q

Primary biliary cirrhosis

A

Non-suppurative, inflammatory destruction of small/medium-sized intrahepatic bile ducts
-not the large or extrahepatic ducts

366
Q

Does primary biliary cirrhosis progress to cirrhosis

A

Not really

367
Q

Primary cirrhosis shows __ __ lesions

A

Florid duct

368
Q

Who gets primary biliary cirrhosis

A

Disease of middle aged women :40-50 year old femmes that live in Northern European countries (England Scotland) or northern US(Minnesota)

North south gradient

Family member with primary biliary cirrhosis

369
Q

Morphology primary biliary cirrhosis

A

Anti-mitochondrial antibodies )anti-PDC-E2)

Florid duct lesion: interlobular ducts are actively destroyed by lymphoplasmacytic inflammation with or without granulomas

Patchy loss of the ducts

Feathery degeneration and ballooned, bile stained hepatocytes with mallory denk bodies

Hepatocyte loss, regenerative hyperplasia, hepatomegaly

Widespread duct loss that leads to cirrhosis and periportal/periseptal cholestasis->end stage

Widespread modularity without the surrounding scar tissu seen in cirrhosis (nodular regenerative hyperplasia)->portal HTN

370
Q

How diagnose primary biliary cirrhosis

A

Biopsy (look for florid duct lesion)

371
Q

Primary biliary cirrhosis causes increased serum what in the asymptomatic individual

A

Alkaline phosphatase and GGT

372
Q

Clinical presentation primary biliary cirrhosis

A

Patients may have progressive fatigue and pruritis

Secondary symptoms may appear: hyperpigmentatoin, xanthelasmas, steatorrhea, vitamin D malabsorption_>osteomalacia/osteoporosis

373
Q

Associated systemic findings of primary biliary cirrhosis

A

Other autoimmune disorders; shorten syndrome (xerostomia, xeropthalmia), sclerosis, thyroiditis, rheumatoid arthritis, raynaud phenomenon, and celiac disease

374
Q

Treat primary biliary cirrhosis

A

Early stage-ursodeoxycholic acid to slow progression

Late stage-liver transplant (ursodeoxycholic acid is ineffective)

375
Q

Primary sclerosing cholangitis

A

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts with dilation of preserved segments
-see beading on radiographs

376
Q

What do you see on radiographs with primary sclerosing cholangitis

A

Beading seen on radiographs

377
Q

Who gets primary sclerosing cholangitis

A

More likely to affect males 20-40 yo

If first degree relative has primary sclerosing cholangitis

378
Q

Associated conditions of primary sclerosing cholangitis

A

IBD(ulcerative colitis) coexists win about 70% of patients with PSC

May lead to biliary intraepithelial neoplasia and cholangiocarcinoma with fatal utcomes

379
Q

__ are found in 65% of patients with primary sclerosing cholangitis

A

PANCAs

Atypical perinuclear antineutrophillic cytoplasmic antibodies

380
Q

Morphology large duct in primary sclerosing cholangitis

A

Neutrophilic infiltration of the epithelium on a chronic inflammatory backgrounf

The inflammation and edema lead to obstruction and scarring that narrow the lumens

381
Q

Smaller ducts morphology primary sclerosing cholangitis

A

Little inflammation with onion skin fibrosis around an atrophic duct lumen that leads to obliteration by a tombstone scar

382
Q

What happens to the liver as primary sclerosing cholangitis progresses

A

The liver becomes cholestasis that can lead to primary biliary cirrhosis

383
Q

Clinical primary sclerosing cholangitis

A

Persistent elevation of serum alkaline phosphatase

There may be progressive fatigue pruritis and jaundice

Acute bouts of ascending cholangitis

Typically progresses over 5-17 years leading to cholestasis

384
Q

Diagnosis primary sclerosing cholangitis

A

Radiology of the larger ducts will show strictures and beading with pruning of the smaller ducts

Diagnosis is made by radiologic imaging of the biliary tree

385
Q

Treat primary sclerosing cholangitis

A

No real treatment

Transplant at end stage

386
Q

Choledochal cysts

A

Congenital dilation of the common bile duct

387
Q

Who gets choledochal cysts

A

Present most often in kids before 10 years old as jaundice or recurring abdominal pain (symptoms of typical biliary colic)
3-4x more likely in females

388
Q

Fibropolycystic disease

A

Group of different lesions int he liver due to congenital malformations of the biliary tree (ductal plate malformation)

389
Q

Presentation fibropolycystic disease

A

Most are incidental findings, but can also present as hepatosplenomegaly or portal HTN without hepatic dysfunction in late childhood or adolescence

390
Q

What is fibropolycystic disease associated with

A

Commonly happens in association with autosomal recessive polycystic renal disease

Patients have an increased risk of cholangiocarcinoma

391
Q

What are the 3 sets of pathological findings of fibropolycystic disease

A

Von meyenburg complexes

Caroli disease

Congenital hepatic fibrosis

392
Q

Von meyenburg complexes

A

Small bile duct hamartomas that are normal if limited, but indicative of FPD if they are diffuse

393
Q

Caroli disease

A

Biliary cysts in isolation that lead to clinical symptoms

Carli syndrome: biliary cysts that occur with congenital hepatic fibrosis

394
Q

Congenital hepatic fibrosis

A

Portal tracts are enlarged by irregular broad bands of collagenous tissue that form septa to divide the liver into irregular islands

  • abnormally shaped bile ducts embedded in the fibrous tissue still connected to the biliary tree
  • may have portal HTN as a result
395
Q

Circulatorydisorders

A

Clinically significant liver function abnormalities do not always develop

Hepatic morphology may be strikingly affected

396
Q

What can compromise the hepatic artery

A

Liver infarcts are rare due to dual blood supply to the liver

Loss of blood supply intrahepatic can lead to localized infarct that is pale or hemorrhagic

Transplanted livers are more likely to become infarcted as they only have blood supple from the arterial system

397
Q

What does hepatic artery compromise result in

A

Impaired blood flow to the liver

398
Q

__ __ obstruction/thrombosis also impairs blood flow to the liver

A

Portal vein

399
Q

Most common cause of impaired blood flow THROUGH the liver

A

Cirrhosis

400
Q

What besides cirrhosis causes impaired blood flow through the liver

A

Physical sinusoidal occlusion

401
Q

What causes physical sinusoidal occlusion

A

Sickle cell disease
Disseminated intravascular coagulation
Eclampsia
Diffuse intrasinusoidal metastatic tumor

402
Q

What may portal vein occlusions cause

A

Esophageal varices

403
Q

What is the most common cause of intrahepatic blood flow obstruction

A

Cirrhosis

404
Q

What is the most common cause of small portal vein branch obstruction

A

Schistosomiasis

405
Q

What causes obliterating portal venopathy

A

HIV

406
Q

Peliosis hepatis

A

Sinusoidal dilation that occurs in any condition in which efflux of hepatic blood is impeded

Blood lakes (due to sex hormones, infection)

407
Q

Right sided heart failure or terminal event

A

Passive congestion

408
Q

Left sided heart failure

A

Hepatic hypoperfusion and hypoxia->ischemic coagulative necrosis of hepatocytes in the central region of the lobule (centrilobular fibrosis)

409
Q

Chronic CHF

A

Cardiac sclerosis with centrilobular fibrosis

Nutmeg liver:hypoperfusion and retrograde congestion

410
Q

Budd chiari syndrome

A

Obstruction of two or more major hepatic veins that leads to hepatomegaly, pain and ascites

411
Q

Prognosis budd chiari

A

High mortality

412
Q

Morphology budd chiari

A

Liveris swollen red purple, and has a tense capsule

There are different areas of preserved or regenerating parenchyma alternating with hemorrhagic collapse

Severe centrilobular congestion and necrosis, or fibrosis if slowly developing

Affected veins may contain thrombi

413
Q

Treatment budd chiari

A

Surgery to create a portosystemic venous shunt permits reverse flow throug the portal vein and improves the prognosis (5 year survival>67%)

414
Q

Sinusoidal obstruction syndrome

A

Obliteration of the terminal hepatic venues by subendothelial swelling and collagen deposition

415
Q

Causes of sinusoidal obstruction syndrome

A

Jamaican bush tea drinkers
3 weeks after stem cell transplant
Cancer patients receiving chemotherapy
Toxic injury to the sinusoidal endothelium

416
Q

Morphology sinusoidal obstruction syndrome

A

Centrilobular congestion, hepatocellular necrosis, and accumulation of hemosiderin macrophages

Obliteration of the lumen of the venue is identified with special stains for connective tissue

417
Q

Clinical sinusoidal obstruction syndrome

A

Histology=gold standard of diagnosis

Clinical diagnosis=tender hepatomegaly, ascites, weight gain, jaundice

418
Q

Passive congestion and centrilobular necrosis and liver

A

Hepatic manifestations of systemic circulatory compromise

419
Q

Liver and bone marrow transplant

A

Graft vs host

Attack the liver

420
Q

Liver transplant and liver

A

Host vs graft

Attacks the liver

421
Q

Acute GVHD time

A

10-50 days

422
Q

GVHD chronic days

A

100+ days

423
Q

Acute GVDH

A

Donor lymphocytes attach the epithelial cells of the liver

Hepatitis with necrosis or hepatocytes and bile duct epithelial cells

Inflammation of the portal tracts and parenchyma

424
Q

Chronic GVHD

A

Portal tract inflammation, selective bile duct destruction, and eventual fibrosis

425
Q

Acute transplant rejection is ___ and chronic transplant rejection is ____

A

Cellular

Vascular

426
Q

Acute(cellular) transplant rejection

A

Characterized by infiltration of a mixed portal inflammatory infiltrate

Associated with bile duct injury and endothelitis

427
Q

Chronic (vascular) transplant rejection

A

Obliteration arteriopathy of small and large arteries leads to ischemic changes int he liver parenchyma

Vanishing bile duct syndrome*

428
Q

What are some hepatic diseasesassociated with pregnancy given that 3-5% of pregnant patients have abnormal liver function tests

A

Viral hepatitis (most common cause of pregnant jaundice)

Hepatic complications that are directly attributable to pregnancy in .1%

Preeclampsia and eclampsia

429
Q

Viral hepatitis and pregnancy

A

HAV, HBV, HCV, or HBV+HBD

HEV infectionruns a more severe course in pregnancy and has a mortality rate of 20%

430
Q

Preeclampsia

A

Maternal HTN, proteinuria, peripheral edema, and coagulation problems

431
Q

When does preeclampsia become eclampsia

A

When hyperreflexia and convulsions

432
Q

HELLP syndrome:subclinical manifestation of preeclampsia

A

Hemolysis

Elevated liver enzymes

Low platelets (thrombocytopenia)

433
Q

Liver in preeclampsia and eclampsia

A

Periportal sinusoids contain fibrin deposits associated with hemorrhage into the space of disse with associated hemorrhagic necrosis

Blood presssure can lead to hematoma and may rupture

434
Q

Clinic preeclampsia and eclampsia

A

Modest to severe elevation of serum aminotransferases and mild elevation of serum bilirubin

435
Q

When does acute fatty liver of pregnancy occue

A

Latter half of pregnancy, often int he third trimester

436
Q

Prognosis acute fatty liver of pregnancy

A

Hepatic dysfunction that can lead to hepatic failure, coma, and death in severe cases

437
Q

In acute fatty liver of pregnancy there is elevated __

A

Serum aminotransferase levels

438
Q

What are symptoms from incipient hepatic failure in acute fatty liver of pregnancy

A

Bleeding, nausea, vomiting, jaundice, and coma

439
Q

Diagnosis of acute fatty liver of pregnancy

A

Characteristic diffuse microvesicular steatosis of hepatocytes on biopsy

May be lobular disarray with hepatocyte dropout, reticulin collapse, and portal tract inflammation (looks like viral hepatitis)

440
Q

Prognosis acute fatty liver of pregnancy

A

Can progress very quickly to hepatic failure and death in a few days

441
Q

How do u treat acute fatty liver of pregnancy

A

Termination of pregnancy

442
Q

Intrahepatic cholestasis of pregnancy presentation

A

Onset of pruritus, followed by darkening of urine and occasionally light (acholic) stools and jaundice in the 3rd trimester

443
Q

Labs intrahepatic cholestasis of pregnancy

A

Serum bilirubin and alkaline phosphatase may be slightly elevated

Bile salt levels are greatly increased

444
Q

Prognosis intrahepatic cholestasis of pregnancy

A

Generally a benign condition to mother

Incidence of fetal distress, stillbirth, and prematurity is moderately increased

445
Q

Nodule hyperplasia of the liver (not a true neoplasm)

A

Single or multiple nodules may develop n a non cirrhosis liver either from focal nodular hyperplasia or nodular regenerative hyperplasia

446
Q

What causes nodular hyperplasia of the liver

A

Due to focal or diffuse alterations in hepatic blood obliteration of portal vein radicle and compensatory flow of arterial blood supply

447
Q

What is focal nodular hyperplasia

A

Benign;well demarcated but poorly encapsulated

Spontaneous mass lesion that appears in a normal liver

448
Q

Who gets focal nodular hyperplasia

A

Young to middle aged adults

449
Q

Morphology focal nodular hyperplasia

A

Tighter than the surrounding liver and is sometimes yellow from steatosis

Central grey-white depressed stellate scar (containing vessels with fibromuscular hyperplasia) that fibrous septa radiate outward from

450
Q

Nodular regenerative hyperplasia

A

Entire liver is transformed into nodules, looks similar to focal nodular hyperplasia, but there is no fibrosis

451
Q

Wha can nodular regenerative hyperplasia lead to

A

Portal HTN

452
Q

What is nodular regenerative hyperplasia associated with

A

Conditions that affect intrahepatic blood flow like HIV or autoimmune

453
Q

Symptoms nodular regenerative hyperplasia

A

Usually asymptomatic, only found at autopsy

454
Q

Morphology nodular regenerative hyperplasia

A

Plump hepatocytes are surrounded by rims of atrophic hepatocytes

455
Q

What is the most common benign liver tumor

A

Cavernous hemangiomas

456
Q

Cavernous hemangiomas are tumors of the ___ ___

A

Blood vessels

457
Q

Morphology cavernous hemangiomas

A

Red blue nodules located directly under the capsule

Vascular channels in a bed of fibrous CT

458
Q

Are cavernous hemangiomas more common in males or females

A

Females

459
Q

How find cavernous hemangiomas

A

Found incidentally or after hemorrhage

-might be mistaken radiographically or intraoperatively for metastatic tumors

460
Q

What are hepatocellular adenomas

A

Benign neoplasm developing from hepatocytes

461
Q

Rupture of hepatocellular adenoma

A

Intrabdominal bleeding that is a surgical emergency

462
Q

What are hepatocellular adenomas associated with

A

Oral contraceptive therapy and anabolic steroids (so sex hormones)
-HEPATOCELLUAR ADENOMAS WERE UNKNOWN BEFORE THE ADVENT OF ORAL CONTRACEPTIVES

463
Q

What are the three types of hepatocellular adenomas

A

HNF1-a inactivated adenomas

B-catenin activated adenomas

Inflammatory adenomas

464
Q

HNf1-a inactivated adenomas are associated with what

A

MODY-3

465
Q

Risk of malignant transformation with HNF-1-a inactivated adenomas

A

No risk of malignant transformation

466
Q

Describe HFN1-a inactivated adenomas

A

Fatty with no atypia

Look for NO staining with liver fatty acid binding protein (LFABP)

467
Q

b catenin activated adenomas associated with what

A

Use of oral contraceptives and anabolic steroids (so sex hormones)

468
Q

B catenin activated adenomas risk of malignant transformation

A

Very high

469
Q

Describe b catenin activated adenomas

A

High degree of dysplasia

Look for glutamine synthetase diffusely and b catenin in the nucleus

470
Q

Inflammatory adenomas associated with what

A

NAFLD

Mutations in gp130 (IL6, JAK-STAT pathway)

471
Q

Inflammatory adenomas risk of malignant transformation

A

Small, but definite risk of malignant transformation

472
Q

Describe inflammatory adenomas

A

Characteristically have in addition areas of fibrotic stroma, mononuclear inflammation, ductular reactions, dilated sinusoids, and telangiectatic vessels

Over express CRP and serum amyloid A

473
Q

What is the most common liver tumor of early childhood

A

Hepatoblastoma

474
Q

What are the types of hepatoblastoma

A

Epithelial

Mixed epithelial and mesenchymal type

475
Q

Epithelial type of hepatoblastoma

A

Small polygonal fetal cell or smaller embryonal cells forming acini, tubules, or papillary structures vaguely looking like liver development

476
Q

Mixed epithelial and mesenchymal type of hepatoblastoma

A

Foci of mesenchymal differentiation with osteoporosis, cartilage, or striated muscle

477
Q

Hepatoblastoma frequently activates ___ pathway

A 
WNT pathway (APC mutation)
*patients with familial adenomatous polyposis frequently develop hepatoblastoma
478
Q

What are hepatoblastoma associated with

A

Familial adenomatous polyposis and beckwith-wiedemann syndromes

479
Q

What is the most common primary malignancy of hepatocytes

A

Hepatocellular carcinoma

480
Q

Risk factors for hepatocellular carcinoma

A

HBV in Asian countries, HCV in USA (both turn chronic)

Alcohol, AFLATOXIN, a1AT, hemochromatosis, NAFLD, wilson disease, adenomas

481
Q

Genetic factors for hepatocellular carcinoma

A

B catenin activation and p53 inactivation (aflatoxin) are the two most common mutational events

May be associated with Il-6/HNF4-a

482
Q

Hepatocellular carcinoma low grade dysplastic nodules: precursor lesion

A

No atypia, have a higher risk of becoming high grade nodules

Shown to be colonial and are probably neoplastic

483
Q

Hepatocellular carcinoma high grade dysplastic nodules:precursor lesions

A

Signs of atypia, have a great risk of becoming HCC and HCC foci are often found already in nodules

484
Q

What is the most important pathway for emergence of HCC in viral hepatitis and alcoholic liver disease**

A

High grade dysplastic nodules

485
Q

Hepatocellular carcinoma morphology large cell change

A

Scattered hepatocytes near portal tracts or septa that are larger than normal hepatocytes with large multiple pleomorphic nuclei

Nuclear cytoplasmic ratio is normal
Large cell change is a marker of increased risk of hepatocellular carcinoma-considered directly pre malignant in hepatitis B

486
Q

Hepatocellular carcinoma small cell change morphology

A

High nuclear cytoplasmic ration and mild nuclear hyperchromasia/pleomorphism

Hepatocytes will commonly form tiny nodules within a single parenchymal lobule

Directly premalignant

487
Q

Hepatocellular carcinoma may appear as what morphologically

A

Large univocal mass
Multifocal, widely distributed nodules
Diffusely infiltration cancer

488
Q

Hepatocellular carcinoma intrahepatic metastases

A

By either vascular invasion or direct extension, become more likely once tumors reach 3 cm in size

489
Q

Hepatocellular carcinoma small, satellite tumor nodules are around what

A

The larger, primary masss

490
Q

Hepatocellular carcinoma vascular metastasis

A

The most likely route for extrahepatic metastasis, espicially by the venous system

491
Q

Hepatocellular carcinoma hematogenous metastases

A

Espicially to the lung, tend to occur late in the disease

492
Q

Presentation of hepatocellular carcinoma

A

Common liver dysfunction symptoms and hepatomegaly

493
Q

_% of patients with advanced hepatocellular carcinoma have elevated a-fetoprotein. What does this mean

A

50

Insensitive as a screening test for pre malignant or early lesions

494
Q

Diagnosis hepatocellular carcinoma

A

Imaging

495
Q

What causes death hepatocellular carcinoma

A

Cachexia, GI or varices bleeding, liver failure, or rarely from tumor rupture and hemorrhage

496
Q

Prognosis hepatocellular carcinoma

A

Die in 2 years

497
Q

Fibrolamellar carcinoma

A

Rare variant of hepatocellular carcinoma

498
Q

Who gets fibrolamellar carcinoma

A

<35

499
Q

Presentation fibrolamellar carcinoma

A

Single large hard scirrhous tumor with fibrous bands coursing through it

500
Q

What is a fibrolamellar carcinoma composed of

A

Well differentiated cells rich in mitochondria growing in nests or cords separated by parallel lamellae of dense collagen bundles

501
Q

Cholangiocarcinoma

A

Second most common primary malignant tumor after HCC

Cancer of the biliary tree coming from bile ducts within and outside the liver

Adenocarcinoma

502
Q

Risk factor for cholangiocarcinoma

A

Liver flukes (opisthorchis, clonorchis)

Chronic inflammation of the large bile ducts

HBV, HCV, NAFLD (same as HCC)

503
Q

Extrahepatic cholangiocarcinoma

A

Perihilar tumors (klaskin tumors) located at the junction of the hepatic ducts (most common)

Common bile duct, posterior to the duodenum

504
Q

Intrahepatic cholangiocarcinoma

A

Only 10% of tumors

505
Q

Premalignant lesion of cholangiocarcinoma

A

Biliary intraepithelial neoplasia (low to high grade: Bi1IN-1,2,3)

3 is the highest grade and has the highest risk of malignant transformation

506
Q

Morphology extrahepatic cholangiocarcinoma

A

Form grey nodules in the bile duct wall that can be diffuse to papillary

Generally small lesions at the time of diagnosis

507
Q

Intrahepatic morphology cholangiocarcinoma

A

Track along the intrahepatic portal tract system that creates a branching tumor within a portion of the liver

508
Q

Cholangiocarcinomas are __ differentiated with __/__ structures lined by __ epithelial cells

A

Moderately well

Glandular/tubular

Epithelial

509
Q

Prognosis cholangiocarcinoma

A

Median time to death is 6 months for intrahepatic, but overall for any location is 14% 2 year survival

510
Q

Clinical presentation intrahepatic cholangiocarcinoma

A

Present as obstruction to bile flow or symptomatic liver mass

511
Q

Clinical presentation of extrahepatic cholangiocarcinoma

A

Biliary obstruction , cholangitis, and RUQ pain

512
Q

Combined hepatocelular and cholangiocarcinoma

A

Suggest an origin from a multipotent stem cell

513
Q

Mutinous cystic neoplasms and intraductal papillary biliary neoplasia

A

May occur as in situation lesion or as invasive cholangiocarcinoma

514
Q

Angiosarcoma

A

Has historic association with vinyl chloride, arsenic, or thorotrast

515
Q

Hepatic lymphomas. Who gets is

A

Middle aged men

516
Q

What are hepatic lymphomas associated with

A

HBV, HCV, HIV< PBC

517
Q

Describe hepatic lymphoma

A

Most are diffuse large B cell lymphomas, then MALTomas

518
Q

Hepatosplanic delta-gamma T cell lymphoma, who get is

A

Young adult males

519
Q

Hepatosplenic delta-gamma T cell lymphoma is a predilection for

A

Hepatic and splenic sinusoids as well as the marrow

520
Q

Is metastases or primary liver cancer more common

A

Metastases

521
Q

Most common places that metastases to the liver

A

Colon, breast, lung, pancreas

522
Q

How does metastases to the liver present

A

Appear as multiple nodular metastases that replace most of the parenchyma and lead to hepatomegaly, but can also appear as just a single nodule

Usually clinically silent until late stage

523
Q

What is the most common congenital gallbladder anomaly

A

A fundus that is folded inwards, creating a phrygian cap

524
Q

More than 95% of biliary tract disease is attributable to ___

A

Cholelithiasis

525
Q

Cholelithiasis

A

Stones of either cholesterol or pigment (bilirubin) that collect in the gallbladder

526
Q

Why are cholesterol stones more common in developed countries and pigment stones more common in developing countries: cholelithiasis

A

Diet

Infections

527
Q

Risk factors for cholelithiasis

A

Middle to older age female

Obesity, metabolic syndrome

Estrogen exposure (OC, pregnancy)

Native Americans

Gallbladder stasis

ABCG8 variant (ABC transport)

528
Q

Pathogenesis for cholesterol cholelithiasis

A

Collect when their concentration increases above the capacity of the bile-precipitate out of bile
Can happen when there is too much cholesterol, crystal nucleation, mucus secretion, or hypomotility

Cholesterol stones are more common in the US and western countries-probably do to diet

529
Q

Pathogenesis of pigment stones

A

Stones of unconjugated bilirubin and inorganic calcium salts

Can happen when there are elevated levels of unconjugated bilirubin in the bile

  • chronic hemolytic anemia
  • severe ideal dysfunction or bypass
  • bacterial contamination of the biliary tract leading to release of beta-glucuronidases(e coli, ascaris, lumbricoides, liver fluke c sinensis)

Arise primarily in te setting of bacterial infections of the biliary tree and parasitic infestations

530
Q

Cholesterol stones morphology

A

In gallbladder

Pure cholesterol stones look pale yellow, finely granular, hard, crystalline palisade

  • stones composed largely of cholesterol are radiolucent
  • sufficient calcium carbonate renders 10-20% of them radiopaque
  • BECOME MORE BLACK and are more lamellated when they are mixed with other substances
531
Q

Pigment stones morphology

A

Black stones are found in sterile bile ducts and are made up mostly of bilirubin, salts, and mucin. Appear friable with speculated and molded contours

50-70% of black stones are radioopaque due to calcium salts

Brown stones are found in infected large bile ducts ; composition is the same, but also have some cholesterol mixed in and are found in ducts with infections. Soap like, greasy, soft, laminated
-radiolucent because they contain calcium soaps

532
Q

Clinical presentation gall stones

A

Usually asymptomatic
Biliary colic=excruciating constant pain

Pain in RUQ that radiates to the right upper shoulder or the back, which is worse after a fatty meal***

533
Q

With cholesthiasis , large stones are less likely to enter the cystic or common ducts and produce obstruction

A

Small stones (gravel) are more dangerous

Gallstones ileus/bouveret syndrome: when a large stone erodes directly into an adjacent loop of small bowel and generates intestinal obstruction

534
Q

Primary complication of gallstones

A

Acute cholecystitis

535
Q

Acute calculous cholecystitis

A

From chemical irritation and inflammation from a stone

  • absence of bacterial infection (though one may develop later in the course)
  • 90% of the time caused by obstruction of the neck or cystic duck by a stone
  • most common reason for an emergency cholecystectomy
536
Q

Acute acalcuous cholecystitis

A

May occur in severely ill patients

  • accounts for the other 10%
  • frequently develops in diabetic patients who have symptomatic gallstones
  • though to result from ischemia (cystic artery=end artery)
  • primary bacterial infection 9salmonella typhi and staphylococci)
  • incidence of gangrene and perforation is much higher in acalculous that’s in calculous
537
Q

Risk for acute cholecystitits

A

Sepsis with hypotension and multisystem organ failure, inspired, major trauma and burns, diabetes, infections

538
Q

Morphology acute cholecystitis

A

Gallbladder is enlarged and tense, may be green-black, bright red, or blotchy

Serosa covering is typically covered in a fibrous exudate

In calculous cholecystitis, the stone is blocking the exit and causes the lumen to fill with cloudy or turbid material that may contain fibrin

539
Q

Gallbladder empyema

A

When the exudate is virtually pure pus

540
Q

Mild gallbladder empyema

A

Wall is thickened, edematous, and hyperemic

541
Q

Severe gallbladder empyema

A

Wall is green-black and necrotic (gangrenous cholecystitis)

542
Q

Acute emphysematous cholecystitis

A

When the gallbladder is invaded by gas forming organisms (clostridium and coliforms)

543
Q

Acute emphysematous cholecystitis

A

When the gallbladder is invaded by gas forming organisms

544
Q

Clinical acute cholecystisis

A

Most patients have experienced pain before the acute attack

The acute attack: progressice pain in the RUQ or epigastric that lasts longer than 6 hours

Mild fever, anorexia, tachycardia, sweating, nausea, and vomiting

545
Q

Acute cholecystitis bilirubin and alkaline phosphatase

A

Slightly elevated

546
Q

What does hyperbilirubinemia in acute cholecystisis cause

A

Obstruction of the common bile duct

547
Q

Treat acute cholecystisis

A

25% will need surgery, other patients will recover in 10 days

548
Q

There is a greater risk of __ and __ in patients that have acalculous cholecystitis

A

Gangrene

Perforation

549
Q

Chronic cholecystisi

A

Chronic inflammation of the gallbladder that is due to stones in 90% of the time

Can be due to repeated acute attacks, but many times is not

At risk population is the same as that for cholelithiasis

550
Q

Morphology chronic cholecystitis

A

Serosa may be dulled to subserosal/subepithelial fibrosis

Wall is variably thickened, has a grey white appearance
Reactive proliferative may lead to fusion of the mucosal folds and give rise to buried crypts of epithelial in the gallbladder

551
Q

Rokitansky-aschoff sinus cholecystisis

A

Outpouching of the mucosal epithelium through the wall

-diverticulum of the gallbladder

552
Q

Porcelain gallbladder chronic cholecystitis

A

Rare calcification of the wall that increases the risk of developing cholangiocarcinoma

553
Q

Xanthogranulomatous cholecystisis chronic cholecystisis

A

Very thick wall and the gallbladder is shrunken, nodular with foci of necrosis and hemorrhage that was triggered by rupture of R-A sinuses. Leads to foam (xanthoastrocytoma) cells

554
Q

Hydrops of the gallbladder chronic cholecystitis

A

Atrophic, chronically obstructed, often dilated gallbladder that may contain only clear secretions

555
Q

Clinical chronic cholecystitis

A

Recurring acute symptoms with intolerance for fatty foods

Beware of bacterial secondary infections, perforation, fistula, and obstruction

556
Q

What is the most common malignancy of the extrahepatic biliary tract

A

Adenocarcinoma of the gallbladder

557
Q

Who is at risk for carcinoma of the gallbladder

A

Women
Chile, Bolivia, northern India, south western ethnic US population

HAVING GALLSTONES

558
Q

Pathogenesis gallbladder carcinoma

A

Biggest risk factor is having gallstones, 1-2% of stone patients get cancer

95% of gallbladder cancers arise in the setting of gallstones

Though that chronic inflammation is reason cancer comes

559
Q

Morphology carcinoma of the gallbladder infiltrating

A

Poorly defined area of mural thickening and induration

More common

560
Q

Morphology carcinoma of gallbladder exophytic

A

Grows intot he lumen (and invades the underlying wall)

561
Q

Is exophytic or infiltrating carcinoma of gallbladder associated wth better prognosis

A

Exophytic

562
Q

Is infiltrating or exophytic more common carcinoma of gallbladder

A

Infiltrating

563
Q

In gallbladder carcinoma, deep ulceration can lead to what

A

Fistula penetration into other viscera

564
Q

In carcinoma of gallbladder, what does it commonly seed

A

Cystic duct, adjacent bile ducts, portal hepatic lymph nodes, peritoneum, GI tract and lungs

565
Q

When is most gallbladder carcinoma found

A

At surgery when he gallbladder is though to have stones

566
Q

What are presenting symptoms of gallbladder carcinoma

A

Same as those for cholelithiasis: abdominal pain, jaundice, anorexia, nausea, vomiting

567
Q

When galll bladder carcinoma is found, what is the prognosis, most of which is already advanced

A

5 years survival is <10%

568
Q

____ oncoprotein is overexpressed in 33-67% of cases of gallbladder carcinoma

A

ERBB2 (Her-2/neu)

Pathology (36 decks)

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