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DT4- Exam 3 > Limjoco- Liver Path X 10 Melissa > Flashcards

Limjoco- Liver Path X 10 Melissa Flashcards

1
Q

The liver connects blood flow between which two entities?

Describe the blood supply to the liver.

A
  • GI system and systemic circulation
  • Liver has DUAL blood supply
    (2/3 = portal vein; 1/3= hepatic artery)
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2
Q

What is the portal triad?

A
  • Hepatic artery
  • Portal vein
  • Common bile duct
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3
Q

Describe blood flow through the liver; where does the portal venous blood mix with blood from the hepatic artery?

Describe the composition of portal venous blood and blood in the hepatic artery…

A

Portal venous blood + Hepatic arterial blood mix in sinusoids–> Central vv’s –> Hepatic vv’s –> IVC–> R. Atrium

  • *Portal venous blood has LOW O2 and ^ nutrients from GI system
  • *Hepatic Arterial blood has ^ O2 and comes from the heart
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4
Q

What are kuppfer cells?

A

Specialized MQs found in liver sinusoids

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5
Q

What do we call the space between endothelial cells and hepatocytes in the liver? What are the cells within this space called? What do they do?

A

Space of Disse: contains STELLATE (Ito) CELLS that mediate such pathological events like liver fibrosis (liver stem cells)

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6
Q

Describe the shape of a liver lobule? An acinus?

How does blood supply change throughout the acinus?

A

A lobule is the area surrounding a central vein; lobules have lowest O2 content in the center (near the vein)

An acinus is the space between a branch of the hepatic artery and the center of a lobule (hepatic vein); O2 content DECREASES with increasing distance from the hepatic artery (approaching the center of a lobule)

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7
Q

The liver metabolizes… (3)

A

carbs, lipids and fats

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8
Q

The liver synthesizes … (5)

A
  • albumin
  • clotting factors: I, II, V, VII, XIII
  • Lipoproteins (VLDL, LDL, HDL)
  • cholesterol
  • glycogen
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9
Q

The liver catabolizes… (3)

A
  • ammonia–> urea (urea cycle***)
  • hormones
  • drugs/ chemicals
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10
Q

The liver stores… (4)

A
  • glycogen
  • TGs
  • Fe, Cu
  • Vit ADEK
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11
Q

The liver excretes… (2)

A

bile and endogenous waste

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12
Q

Describe the liver’s role as blood reservoir; under what type of stimulus will the amount of stored blood increase?

A

Sympathetic stimulation INCREASES the amount of blood stored in the liver

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13
Q

How does the liver play a role in endocrine function?

A
  • synthesis of vitamin D

- removal of circulating hormones i.e. glucagon, etc.

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14
Q

What are the two serum transaminases and how are they indicative of liver function? What is their normal role in liver function

A
  • Aspartate amino transferase (AST)
  • Alanine amino transferase (ALT)

AST and ALT will INCREASE in serum in response to hepatocyte injury; normally facilitate amino acid metabolism

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15
Q

What is the function of alkaline phosphatase?

Elevated ALP in serum indicates what kind of disease?

A
  • ALP removes PO4 groups (bile duct cells + liver cells)

- Elevated in CHOLESTATIC disease

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16
Q

Gamma Glutamyl Transpeptidase: what is the function of this enzyme? What does elevated GGT in serum indicate?

A
  • GGT is involved in glutathione metabolism + drug detox

- ^ GGT + ^ ALT in serum indicated HEPATOBILIARY DISASE

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17
Q

What is the most sensitive indicator for liver disease?

A

^^^ serum GGT

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18
Q

What does albumin do? How is serum albumin content changed in liver disease?

A
  • Albumin maintains normal oncotic pressure

- LOW serum albumin is indicative of liver disease (degree depletion NOT indicative of disease severity)

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19
Q

What is the #1 cause of acute hepatitis?

A

viral hepatitis

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20
Q

List some potential causes of acute hepatitis?

Do not memorise list; each will be discussed independently; just for overview

A
  • viral hepatitis
  • acetaminophen toxicity
  • idiosyncratic drug response
  • ETOH
  • Autoimmune hepatitis
  • metabolic disorders (Reye, acute fatty liver of preggos)
  • circulatory disorders (Budd- chiari, right heart failure)
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21
Q

Describe spotty/ lytic necrosis; with what disease state is it associated?

A

Acute Hepatitis

- clusters of small lymphs surrounding liver cells

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22
Q

Describe ballooning degeneration; with what disease state is it associated?

A

Acute Hepatitis

- fluid filed hepatocytes

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23
Q

Describe interface hepatitis; with what disease state is it associated?

A

Acute Hepatitis

- lymphocytic infiltrate surrounds portal tract and spills over limiting plate into lobule

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24
Q

Describe confluent necrosis; with what disease state is it associated?

A

Acute hepatitis

  • many dead cells with pale cytoplasm
  • possible ‘functional islands’ of spared tissue
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25
Q

Describe bridging necrosis with what disease state is it associated?

A

Acute Hepatitis

  • ^^^ fibroblasts
  • spans 2 architectural structures (i.e. portal vein and hepatic artery, etc.)
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26
Q

Three possible clinical outcomes of acute hepatitis?

How does confluent necrosis or chronic injury influence the liver’s regenerative capacity?

A
  • spontaneous resolution with supportive tx.
  • acute liver failure
  • chronic hepatitis

**regeneration of hepatocytes will continue in spite of chronic injury or confluent necrosis

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27
Q

What are 6 clinical manifestations of acute hepatitis?

A
  • encephalopathy (acute)
  • coagulopathy –> GI bleeds
  • acute renal failure (pre renal)
  • infection, sepsis
  • respiratory failure
  • CV collapse
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28
Q

What is Acute Hepatic FAILURE?
What typically causes it?

When and with what two comorbidities will it present?

A

Chronic liver disease +/- compensation–>
Decreased hepatocyte # or function–> Acute Hepatic Failure

  • Appears within 26 wks of initial liver injury
  • Presents with coagulopathy and encephalopathy
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29
Q

What are the three ways that acute hepatic failure can present PATHOLOGICALLY?

A
  • # 1: chronic liver disease changes
  • massive hepatic necrosis (80-90% loss)
  • non-necrotic AHF ( i.e. reye’s, preggos, drug tox)
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30
Q

How does Acute Hepatic Failure manifest clinically?

skin, blood, neuro?

A
  • Jaundice (bilirubin retention) + N/ V
  • Hyperammonimia
  • Bx Changes, Rigidity, hyper-reflexia, EEG Changes
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31
Q

Describe the coagulopathy associated with acute hepatic failure: 4

A
  • decreased clotting factor production
  • ^ PT (decreased F VII)
  • thrombocytopenia (marrow suppression, hypersplenism)
  • DIC (failure to clear ACTIVATED factors from circulation)
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32
Q

What is micro vesicular steatosis and with what is it associated? What are three things that can cause this?

A
  • Histological appearance of AHF in which fat globules fill cells bit not enough to push nuclei into periphery
  • Asstd with fatty liver of PREGGOS, valproate or tetracycline toxicity
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33
Q

What are the lab findings associated with AHF?

A
  • ^ AST, ^ALT
  • Hypoalbuminemia
  • Hyperammoemia
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34
Q

What are the ABCDEFs of AHF?

A 
Acetaminophen, HepA, Autoimmune 
Hep B 
Hep C, Cryptogenic 
Drugs (+ toxins), Hep D
Hep E, Esoterie cases (wilson's, budd chirari)
Fatty changes (microvesicular type)
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35
Q

What happens in hepatorenal syndrome?
What will make it better?
Describe the progression…

A

Pre renal failure without intrinsic morphologic abnormalities; renal function will normalize with improved hepatic function

systemic vasodilation–> compensatory renal vasoconstriction–> decreased GFR

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36
Q

Define Chronic Liver Disease; what is the endgame?

A

Liver disease, abnormal testing that lasts, progressive fibrosis that lasts LONGER than 6 mos

End result = cirrhosis

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37
Q

Describe the pathogenesis of liver CIRRHOSIS:

A

Damaged hepatocyte–> ROS/ Gfs/ TNF/ IL1–>
*ACTIVATE STELLATE CELL–> TGFB, SM actin, GFAP–>
Collagen deposition–> Fibrosis–> Cirrhosis

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38
Q

Describe the histological path changes to the liver in liver cirrhosis: (4)

A
  • FIBROSIS surrounding multiple adjacent lobules

- Regenerative NODULES in canals of Hering (micro)

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39
Q

Describe the early and late clinical manifestations of liver cirrhosis:

A

asx–> nonspecific (weak, anorexic) sx–> progressive liver failure–> portal HTN–> ascites, portal-systemic shunts, congestive HSM, encephalopathy

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40
Q

What is bile? Where is it produced?

What are its 4 functions?

A

Complex fluid of bile acids + bilirubin made in LIVER

Flows through biliary tract into sm intestine:

1) Emulsification + micelle formation = absorb dietary fat
2) Bicarb = neutralize gastric acid
3) Elimination: cholesterol, protein bound organic molecules, heavy metals, lipophilic metabolites

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41
Q

What is bilirubin? How much of bile does it comprise?
How is it clinically relevant?
What are its two forms?

A

Heme breakdown products; 2% of bile

  • makes bruises and jaundiced people yellow
  • conjugated and unconjugated
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42
Q

Contrast conjugated and unconjugated bilirubin:

A

Unconjucated: water INSOLUBLE + TOXIC; crosses BBB in babies to cause kernicterus

Conjugated: water SOLUBLE, nontoxic, excreted in urine

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43
Q

What are bile salts? What are the two important ones called? What is their function?

A
  • Bile acids (cholesterol breakdown products) conjugated to Taurine or Glycine
  • Cholic acid, chenodeoxycholic acid
  • Act as detergents to solubilize water insoluble lipids
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44
Q

Cholestasis: define the term

A

Decreased bile flow–> accumulation of substances normally excreted in bile

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45
Q

95% of bile acids are reabsorbed from WHERE in the intestine and returned to the liver???

A

TERMINAL ILEUM

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46
Q

If there is an issue with excessive bilirubin production, what type of bilirubinemia would occur?

What are 3 different pathological states that could induce such bilirubinemia?

A

Heme–> Heme oxygenase// Biliverdinreductase–> UNCONJUCATED Hyperbilirubinemia

Potential causes:

  • hemolytic anemia
  • hematoma/ internal hemorrhage
  • ineffective erythropoiesis (PA, thalassemia)
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47
Q

Failure of bilirubin uptake or binding would cause what type of bilirubinemia?

What are 4 different pathological states that could induce such bilirubinemia?

A

Bilirubin-Alb complex–> NOT transported across cell mb and taken up by protein carrier–>
UNCONJUCATED Hyperbilirubinemia

Potential causes:

  • Hepatocellular injury
  • Drugs (interference with metabolism of protein carriers)
  • Physiologic jaundice of the newborn
  • Gilbert’s syndrome
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48
Q

Failure to conjugate bilirubin in the hepatocyte ER involves failure of what enzyme?

What type of bilirubinemia will ensue?
What are 4 potential causes of such bilirubinemia?

A

Failure of UDP Glucuronyl Transferase–> Bilirubin NOT conjugated withglucuronic acid in ER–>
UNCONJUCATED Hyperbilirubinemia

Potential causes:

  • Breast milk (???)
  • Genetic UGT1A1 deficiency (Crigler-Najjar)
  • Gilbert’s syndrome
  • Diffuse hepatitis
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49
Q

Failure to excrete bilirubin will result in what type of bilirubinemia?

What are 3 potential causes of excretion failure?

A

CONJUGATED bilirubin diffuses through cell into bile canaliculus–> FAILS to get excreted into bile–>
CONJUGATED Hyperbilirubinemia

Potential causes:

  • Dublin-Johnson, Rotor (deficient canalicular membrane transporter)
  • Autoimmune cholangiopathies
  • Ductal obstruction
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50
Q

Describe the pathway of bile cycling when excreted into small bowel:

A

Bile excreted into small bowel + B-glucuronidases–>
Free bilirubin + Reduction Rxn–> Pyrroles + Urobilinogen–>
80% Urobilinogen excreted in feces; 20% reabsorbed in ileum–> return to liver –> re-excreted in bile or urine

Note: B-glucuronidases come from gut bacteria

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51
Q

Describe the histological appearance hepatocytes affected by cholistasis within bile canaliculi:

A

Clusters of MQs + feathery degeneration of hepatocytes w/ clear cytoplasm

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52
Q

What are the clinical implications for intrahepatic vs extra hepatic cholestasis?

A
  • Intrahepatic can ONLY be treated with liver transplant

- Extrahepatic can be cured by surgical means (less sever then transplant)

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53
Q

What are the clinical manifestations of the following:

1) ^ serum bilirubin
2) ^ serum bile acids
3) malabsorption of fat
4) Malabsorption of ADK
5) ^ serum cholesterol

A

1) jaundice
2) pruritis
3) steatorrhea
4) hemorrhaging/ clotting disorders
5) Xanthomas

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54
Q

List the 6 Hepatotropic viruses with affinity for the liver.
Which cause acute hepatitis?
Which cause chronic hepatitis?
What is a mnemonic for how one of the viruses can be transmitted?

A

A, B, C, D, E, G

Vowels A, E- NEVER CHRONIC (except HepE in preggos)
Consonants B, C, D- CAN BE CHRONIC
Hep B transmitted via Blood, Birthing, Bonking

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55
Q

List 5 viral infections that are not specifically hepatotropic but can cause hepatitis:

A
  • EBV, CMV, HSV
  • Adenovirus (immunosuppressed, neonates)
  • Yellow fever

I remember HAYCE viruses.

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56
Q

Which hepatitis virus is more often chronic than not?

A

Hepatitis C

  • 80% get chronic disease
  • 20% of ppl w chronic disease will develop cirrhosis
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57
Q

Describe the typical course of ACUTE viral hepatitis (what are the 4 stages of infection?):

A
  • Weeks 1-2: Incubation (asx + most infectious towards end)
  • 2 wks: Symptomatic Pre-Icteric (flu sx)
  • 4 wks: Icteric (jaundice, dark urine, clay stool, HM), lasts 6 wks
  • 6-8wks: Convalescence (less jaundice)
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58
Q

Describe the lab findings asstsd. with ACUTE viral hepatitis:

A
  • ^ transaminases
  • hyperbilirubinimia
  • viral serology
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59
Q

Define CHRONIC viral hepatitis:

A

ANY evidence of continuing/ relapsing disease lasting LONGER than 6 mos

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60
Q

Describe the carrier state for viral hepatitis:

A

Harbor organism without signs or sx of infection; patient is a RESERVOIR for future infection

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61
Q

How is hepatocellular damage mediated in viral hepatitis?

A

Mediated by T CELL DEFENSE MECHANISM:
T cells activated in response to infected cells–>
Necroinflammatory activity + Apoptosis

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62
Q

HAV:
Family, Genus, Genome, Envelope?
How is the virus transmitted?

A

Family: Picornaviridae
Genus: Hepatovirus
(+) ssRNA, Naked

Fecal oral transmission (water, shellfish*)

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63
Q

Describe the differences in infection caused by Hep A in endemic developing countries vs. developed countries

A

Endemic countries: Poor sanitation; MILD CHILDHOOD disease (most have immune Abs by 10yoa)

Developed countries: No herd immunity; more SEVERE ELDERLY DISEASE

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64
Q

Describe the Ab response to Hep A infection; which Igs are made first? Which are made later?

Which can be directly detected?

A

Acute symptomatic infection–> ^ IgM
IgM declines over mos–> ^ IgG confers lifelong immunity to ALL STRAINS of Hep A

IgG CAN NOT be directly detected

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65
Q

When does fecal shedding of HAV occur?

A
  • 2-3 weeks BEFORE jaundice
  • 1 wk AFTER START jaundice

F/O or close contact with infected individuals during this time period is how infection spreads

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66
Q

How do we diagnose HepA infection? Is there a carrier state? De we biopsy the liver? How often do patients relapse infection?

A
  • Hx of travel to endemic areas
  • Exclude drug-induced disease (Acetaminophen OD)
  • Do not biopsy liver

No chronic or carrier state, rarely relapse

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67
Q

HBV:
Family, genome, structure
Describe the 3 important antigens.

A

Hepadinaviridae

  • Circular dsDNA
  • Enveloped
  • Carries DNA pol, reverse transcriptase
  • Hbx protein = transcriptional activator
HbcAg = core antigen 
HbsAg = surface/ envelope glycoprotein antigen 
HbeAg = indicates infectivity
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68
Q

What is the dane particle?

A

Dane pareticles are small, sausage shaped surface antigens (virons) that infect hepatocytes

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69
Q

Describe the course of Ig production in HBV infection; which are made first and which are made later?

A

IgM made at first–> IgG made agains HbcAg after several mos infection

**Note IgM is always the first Ig made in response to infection :)

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70
Q

Describe how mode of HBV transmission is influenced by geography (high, medium, low prevalence regions)

A
  • Vertical transmission (parturition) in ^ prevalence regions
  • Horizontal transmission intermediate prevalence regions
  • Sexual/ IV drug transmission in LOW prevalence regions
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71
Q

Describe the typical course of HBV disease.
How common is chronic disease and what risks does it pose?
Who is more likely to get chronic HBV infection?
How is infection cleared?

A
  • Typically self limited, spontaneous resolution/ recovery
  • Chronicity = RARE; ^ risk HCC
  • Chronicity more likely in YOUNGER patients + immunocompromised (i.e. vertical transmission to baby)

**Patients will clear infection if CD4, CD8 cells make IFN-Y and clear infected cells (like all viral infections?) Failure = chronicity

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72
Q

Why is a complete cure to HBV difficult to attain?

How do we treat disease?

A

Virus inserts itself into host DNA–> inhibits effective immune response via production of HbsAb–> infection persists

Only treatment is to slow infection and limit cirrhosis/ progression to HCC

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73
Q

HCV:
Family, genome, structure?
What accounts for the variety of HCV genotypes?

A

Flavaviridae
(+) ssRNA, enveloped, codes for 1 polyprotein that gets cleaved

*RNA-Pol has poorfidelity–> multiple genotypes and subtypes get made

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74
Q

Why is it difficult for us to develop a HCV vaccine!?

A

E2 envelope protein = target for anti-HCV Abs

  • *E2 envelope protein is the MOST VARIABLE region of the genome sequence; thus it commonly escapes neutralizing Abs
  • *^^ genomic instability/ antigenic variability = IMPOSSIBLE TO MAKE VACCINE
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75
Q

Why is there such a high rate of chronicity in HCV infection?

A

IgG made after HCV infection DOES NOT confer immunity (high genomic instability of HCV)–> recurrent reactivation of preexisting infection/ emergence of mutated strain are common events

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76
Q

What are the two most common means if HCV infection in the US?
How common are transfusion related infections?
Are you more likely to get HCV or HIV from needle stick?
What % HCV infections are perinatally transmitted?

A 
#1 = IV drug use
#2=  (Unprotected) sexual promiscuity
  • Transfusion associated infections ~ 0 bc good screening
  • More likely to get HCV than HIV from a needle stick
  • Perinatal infection accounts for 6% HCV (vs. 20% HBV)
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77
Q

Describe the clinical course of HCV infection; how severe is the clinical course?

A

4-26 wks Incubation (asx)–>
HCV RNA in blood + ^AST/ ^ALT for 1-3wks–>
Chronic hepatitis–> 20% Cirrhotic

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78
Q

How is HCV treated?
Which viral genotypes respond best to treatment?
Which host genotypes respond best to treatment?

A
  • Pegylated IFN-a
  • Ribavirin

Viral genotypes 2, 3 = Best
Host genotype IL28B (IF-lambda) = Best

Rx QUESTION; make sure you know which IFNs are use to treat which things i.e. “a” for viruses like HCV “b” for MS, etc. I’m sure you know but this was just a friendly reminder

Yes, I remember, Inf-BETA treats the BRAIN in MS. B for Brain, which means A is NOT the brain, it is the virus one. And gamma is for random shit

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79
Q

What is an absolute requirement for HDV infection?

A

HBV infection!

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80
Q

Describe the course of HDV infection; how about confection w HBV?
How can you get an HDV superinfection?

A
  • Typically self limited EXCEPT in IV drug abusers (ACUTE LIVER FAILURE)
  • HBV confections are typically ACUTE and self limited

HDV SUPERINFECTION results when patient carries HBV and gets infected with HDV 30-50 days later–> SEVERE ACUTE HEPATITIS

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81
Q

Describe the HDV genome.
How does the virus replicate?
What is the antigenic target for the host’s immune system?

A
  • ssRNA genome replicates using HOST RNA-pol

- Delta Antigen (HDAg) targeted by host immune system (there is a small and a large)

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82
Q

Where is HEV epidemic?
Where are the more more HEV than HAV cases?
Where is HEV harbored in developed countries?
Which population is exceptionally vulnerable to HEV infection?

A

Epidemic in Asia, Africa, ME, Mexico
India has more HEV than HAV
Developed countries harbor HEV on pig farms

**PREGGOS GET HEV REALLY BAD!

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83
Q 
HEV: 
Family, genome
When are the virons shed? 
What do the labs look like during clinical infection? 
Describe the clinical course?
A

Hepeviridae; (+)ssRNA

  • Virons shed detectible in stool + serum prior to sx; shed throughout acute illness
  • Labs: ^AST/ALT + IgM Anti-HEV
  • Self limited infection lasts 4-6wks
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84
Q

How is a liver biopsy different based on different causes of hepatitis?

A

It isn’t; liver biopsies are the same whether hepatitis is viral, autoimmune, or drug induced

**Need clinical hx to dx cause

EXCEPT PLEASE NOTE: SHE DOES WRITE THIS, BUT BECAUSE SHE IS AN ACTUAL BITCH……
-Per Basem: “In her review, she stated, you should look at robbins/ be able to differentiate Hep B and C on histo.” (He posted a picture of this to FB if you do not have robins/ cannot find it online.)

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85
Q

What are the uses for liver biopsy? (4)

A
  • confirm dx
  • exclude simultaneous conditions (i.e. drug induced)
  • extent of inflammation, injury, fibrosis
  • monitor treatment effectiveness
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86
Q

Ground glass pattern hepatitis is associated with which cause?

A

HBV

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87
Q

What infectious agent will cause hepatitis with cowry bodies?

A

HSV hepatitis (bc cowry’s are HSV)

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88
Q

What kind of hepatitis will cause apoptotic bodies?

A

Viral causes of hepatitis will yield apoptotic bodies

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89
Q 
Define autoimmune hepatitis. 
What are the typical lab findings associated with this disease?
What is found on liver biopsy? 
What is the definitive Dx?
Is there a good treatment? 
What is the prognosis of disease?
A

Idiopathic CHRONIC, progressive autoimmune attack of hepatocytes

  • ^ AST, ALT + serum autoAbs, polyclonal serum Igs
  • NECROINFLAMFMATION on liver biopsy
  • Definitive dx = BIOPSY
  • Excellent response to immunosuppressants
  • WILL DIE WITHOUT TREATMENT
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90
Q

Which population has the highest incidence of autoimmune hepatitis?

A

With northern european females (but really anyone can get it)

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91
Q

What is Type 1 autoimmune hepatitis? Who gets it? What are the serologic markers (2)?

A

Type I autoimmune hepatitis is found in middle aged/ older adults in the US

  • ANA
  • ASMA (anti-smooth muscle Ab)
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92
Q

What is Type 2 autoimmune hepatitis? Who gets it? What are the serologic markers (1)?

A

Type II autoimmune hepatitis is found in KIDS + TEENS in southern europe
- Anti-LKM-1 (attacks CYP-2D6 on plasma mb of cell)

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93
Q

Describe the three potential etiologies behind autoimmune hepatitis:

A
  • idiopathic
  • environmental trigger (drug/ infection)
  • genetic predisposition (HLA association established)
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94
Q

What are the three ways that autoimmune hepatitis might present?

A
  • Asymptomatic incidental finding
  • Asstd. w other autoimmune diseases
  • Acute hepatitis w/ flu like sx
  • Fulminant Hepatitis w. encephalopathy
  • Overlap syndrome (AIH-PBC, AIH-PSH) w biliary disease
  • Cirrhosis
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95
Q

Describe the course of treatment for AIH:

A

Immunosuppression with prednisone or asothioprin; type 2 non responders may dry different treatments

50% will relapse on treatment withdrawal, therefore treatment is a life-long process

Patients may require transplant (20% transplant recipients recur)

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96
Q

What are Xenobiotics and how are they relevant to the liver?

A

These are therapeutic agents and environmental toxins that are metabolized in the liver via immune mechanisms (possibly to toxic compounds)

Can cause cholestasis–> fulminant hepatitis

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97
Q

How do we identify if liver injury is associated with xenobiotics? (2)

A
  • temporal association w exposure and injury

- recovery upon withdrawal of the agent

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98
Q

Describe the histo changes and liver injury caused by OCPs (2 potential problems):

A

Cholestatic injury OR Vascular lesions

Cholestatic Injury: Bland hepatocellular cholestasis without inflammation (feathery degeneration)

Vascular lesions: Budd chirari syndrome, pelliosis hepatitis (blood filled cavities WITHOUT endothelial lining)

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99
Q

Describe the histo chances and liver injury caused by acetaminophen toxicity:

A
  • Hepatocellular necrosis

- Spotty necrosis, massive necrosis, or chronic hepatitis changes

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100
Q

Describe how MTX can hurt the liver (histo and type of injury):

A
  • Fatty liver disease OR fibrosis/cirrhosis

- FLD: large + small droplets fat seen on histo

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101
Q

Describe the histo changes and liver injury associated with ETOH abuse?

A

Fatty liver disease

  • Large/ small fat droplets OR…
  • Steatohepatitis with Mallory-Denk bodies
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102
Q

Which two xenotoxins are capable of causing fibrosis and cirrhosis? How does this look on histo?

A

Alcohol (not necessarily just ETOH, but “Alcohol”) and MTX

- Periportal + pericellular fibrosis

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103
Q

OCPs can cause what hepatic neoplasm?

A

hepatic adenoma

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104
Q

Alcohol can cause what hepatic neoplasms? (2)

A
  • hepatocellular carcinoma

- cholangiocarcinoma

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105
Q

What is meant by predictable vs. unpredictable hepatic injury by xenotoxins?
What are two agents that can cause unpredictable injury?
What is one agent that can cause a predictable injury?

A

Predictable
- Dose dependent changes i.e. acetaminophen toxicity

Unpredictable/ Idiosyncratic

  • Immune mediated destruction
  • Direct cytotoxicity (Chlorpromazine, Halothane**)
106
Q

How common is acetaminophen OD? How many people die each year?

A

1 cause acute liver failure in US today; 500 die each year; transplant is typically required

107
Q

Define Alcoholic liver disease.

Describe the three forms of liver injury it can cause.

A

Excessive ETOH consumption over long period–> liver changes

  1. steatosis (fatty change)
  2. Alcoholic Seato-Hepatitis (necroinflammatiory change)
  3. Steatofibrosis (cirrhotic change)
108
Q

Which is more common, micro or macrovasicular steatosis?

A

macro

109
Q

Describe the gross appearance of a liver with steatosis.

Can this be reversed? Describe the pathogenesis of this fatty change.

A

Enlarged, soft and greasy on sectioning + micro/macrovesicular change

Reversible with abstinence

Pathogenesis:
^^ lipid synthesis–> abnormal lipoproteins–> ^^ peripheral fat catabolism

110
Q

What three things do we look for histologically in steatoHEPATITIS?

A
  • fat cells
  • inflammation
  • necrosis
111
Q

What are mallory denk bodies?

With what disease state are they associated?

A
  • ALCOHOLIC HEPATITIS

- Think eosinophilic inclusion (cytokeratin filaments) seen in hepatocytes

112
Q

What is the neutrophilic reaction seen in alcoholic hepatitis?

A

Neutrophilic infiltrate in areas of hepatic necrosis–> ^ ROS

113
Q

How many grams ETOH are required to incite mild fatty change in men? women?

A 
men = 80gms/ day
women = 20gms/ day

Leah gets this on vacation; I get this on weekends when Jeff visits

114
Q

Who is more susceptible to alcoholic liver disease, men or women? Why (3)
Which ethnic groups are more susceptible? (1)
Which ethnic group is associated with ALDH2 polymorphism? (1)

A

Women ^^ susceptible

  • ^ body fat
  • less ALD
  • ^^estrogen, ^^LPS receptor K cells)

AA drinkers more likely to get cirrhosis
Asians have ALDH2 (^^acetaldehyde)

115
Q

What are two factors that are synergistic with ETOH that can cause WORSE liver disease?

A
  • Fe overload

- HCV, HBV infections

116
Q

How does alcohol mediate hepatic damage (2)

A
  • Steatosis

- Mitochondrial injury (oxidative stress, hypoxia) –> this is why ^^AST

117
Q

What are three results of hepatocellular steatosis?

A
  • ^ reduced NADH–> ^ lipogenesis, LESS FFA oxidation–>
    ^ Lipoproteins (shunt substrate to lipid synth pway)
  • impaired lipoprotein synthesis
  • increased peripheral fat catabolism–> ^FFA
118
Q

What does a cirrhotic liver look like grossly and on histo?

A

Small, nodular, firm

Histo: nodules of hepatocytes surrounded by fibrous bands

119
Q

Hepatic Steatosis:

  • Gross appearance?
  • Lab findings?
A

Hepatomegaly

^ bilirubin, ^ ALP

120
Q

Alcoholic Hepatitis:

  • How long does it take to get this? Clinical findings?
  • What are the associated lab findings?
A
  • 15-20 years drinking OR binge
  • Malaise, weight loss etc. possible acute cholestatic syndrome
  • ^ bilirubin, ^ALP, ^Neutros, ^AST/ALT ratio (over 2/1)

AST is high because alcoholics get SAUCED.

121
Q

Alcoholic Cirrhosis:
What are the complications?
How does it present clinically?
What are the associated lab findings?

A

Portal HTN + malnutrition, etc.

  • Malaise, weakness, anorexia + jaundice/ ascites
  • ^AST/ALT, ^bilirubin, +/- ^ALP, anemia, low proteins

Note: 20% cirrhotics have other disease w clinically silent cirrhosis

122
Q

What is the major histo finding associated with liver cirrhosis of any kind?

A

FIBROSIS. FIBROSIS. FIBROSIS.

**This indicates progressive injury no matter what

123
Q

Describe the histo of alcoholic (or any) liver cirrhosis:

A

Activated stellate cells in centrilobular sinusoids, perisinusoidal and pericellular fibrosis

124
Q

What are the possible sequelae of alcoholic cirrhosis? (5)

A

Death/ coma, bleeding, sepsis, hepatorenal syndrome, HCC

125
Q

What is nonalcoholic fatty liver disease (NAFLD)?
How does this differ from nonalcoholic fatty liver cirrhosis (NAFLC)?
What type of cancer is associated with this spectrum of diseases?

A 
#1 LIVER CHRONIC LIVER DISEASE IN THE US
Associated with DM2, obesity; essentially same changes seen in alcoholic fatty liver disease w.o hx ETOH abuse
NAFLC is a more progressive form of NAFLD
#1 CAUSE ^ LIVER ENZYMES IN THE US

***Associated with HCC

126
Q

What is the gold standard for dx of NAFLD?
What would you see on imaging?
How do we grade/ stage the disease?

A

Liver biopsy = gold standard
Fat accumulation in liver seen on biopsy

Grade = inflammation, necrosis, steatosis 
STAGE = FIBROSIS (cirrhosis @ this point)
127
Q

Hepatic Steatosis of any kind is defined as..

A

MORE THAN 5% fat cells in liver parenchyma + ^ enzymes

WITHOUT inflammation, cell death, fibrosis

128
Q

Describe the clinical and lab findings associated with NAFLD:

A

Clinical: HM, fatigue RUQ pain w.o hx ETOH abuse
Labs: ^ALT, ^ALP, AST/ALT ratio LESS THAN 1

129
Q

What are the first and second hits in the two hit model of NAFLD development?

A

Hit 1: Insulin resistance –> Hepatic steatosis

Hit 2: Hepatocellular oxidative injury/ necrosis/ inflammation –> NAFLD

130
Q

Describe the pathogenesis of NAFLD; what are the two cytokines important to this process?

A

Immune Mediated
^ dysfunctional visceral fat + LOW adiponectin–>
^ TNF-a, ^IL-6–> Fat apoptosis–> ROS–> mitochondrial, cell membrane damage

131
Q

What is cryptogenic cirrhosis?

A

90% fatty liver (Burned out NAFLD)

132
Q

Describe the findings in pediatric NAFLD; what is the biggest danger for these kids?

A
  • MORE diffuse steatosis
  • MORE portal fibrosis
  • MONONUCLEAR infiltrate in portal and lobule (vs neutros in adult)

**Kids have ^ risk HCC

133
Q

Describe the cycle of bilirubin synthesis and transport; what are the major events and enzymes involved?
Where do they take place?

A

Spleen MQs:
Heme–> Biliverdin –> Unconjugated Bilirubin
Heme Oxygenase
Biliverdin reductase

Unconjugated Billirubin/ Albumin in plasma

Liver:
Unconjugated Billirubin–> Conjugated Bilirubin
UDPGT

134
Q

IMPORTANT: Enzyme responsible for conjugating bilirubin in the liver?

A

Glycuronyl Bilirubin Transferase (UDPGT)

135
Q

Which infants are more susceptible to physiological jaundice?
What type of jaundice is this?
What are 4 features of infant physiology that make this likely to happen?
How do we treat it and by when does it typically subside?

A
  • More common in preterm infants
  • Unconjugated hyperbilly

Causes:

  • immature liver (low UDPG + ligandin)
  • Shorter RBC lifespan
  • HIGHER RBC mass
  • Birth trauma

Treat with blue lamp (H2O soluble Z isomers); should reside in 14-21 days

136
Q

What is breastmilk jaundice and why dose it happen? How long does it last and and how is it treated?

A

Breastmilk has B-glucuronidase (deconjugates bilirubin); will last longer than physiological jaundice

Discontinue breast feeding to treat

137
Q

What is the ultimate danger associated with neonatal hyperbilirubinemia?

A

KERNICTERUS: Unconjugated bilirubine crosses BBB and is toxic to basal ganglia

138
Q

Two conditions that ^ risk of Hyperbilirubinemia and kernicterus?

A
  • G6PD deficiency

- Hereditary Spherocytosis

139
Q

Which gene encodes UDPGT?

What happens when it is mutated?

A

UGT1A1 Gene encodes UDPGT, the enzyme responsible for conjugating bilirubin with mono/ diglucuronides

Mutation results in hereditary hyperbilirubinemias

140
Q 
Crigler Najjar I vs. Crigler Najjar II 
What happens in these diseases? 
Which is more severe? 
What are the inheritance patterns of each?
How are they diagnosed?
A

UGT1A1 mutation–> UDGPT deficiency–> Unconjugated hyperbilirubinemia

Crigler Najjar I (AR)

  • More severe; presents in infancy w kernicterus, lose vision and hearing, hypotonia
  • Fatal without transplant + lifelong photoTX

Crigler Najjar II (AD, but FA says AR…)

  • Incomplete UDPGT deficiency
  • Mild jaundice, not fatal
  • **Treat with phenobarbital (via FA)

Diagnose with liver biopsy

141
Q

Dubin Johnson Syndrome:
What is the inheritance pattern for this disease and what gene is mutated?
How does the disease manifest? Describe gross path changes***?

A

AR

  • Mutated MRP2: codes for protein that transports conjugated billirubin to the canaliculi
  • Results in benign relapsing CONJUGATED hyperbilirubinemia

LIVER TURNS BLACK!!! Melanin infiltrate
Dublin is Ireland. Irish people drink BLACK BEER–> BLACK LIVER

142
Q

Gilbert Syndrome:

Inheritance pattern; lab findings; clinical findings

A

AR condition causing asymptomatic/ mild (unconjugated) jaundice w stress

  • No clinical consequences; no treatment needed
143
Q

Define Cholestasis:

A

Impaired bile formation/ secretion/ flow (extra or intra hepatic)–> Accumulation of bile pigment in hepatic parenchyma

144
Q

Describe the clinical manifestations of cholestasis?
What happens to the skin and GI tract?
What do lab tests indicate?

A

Skin problems: Jaundice, xanthomas, puritis
GI: Intestinal malabsorption
Labs: ^ALP, ^GGT

145
Q

What are some of the causes of a large bile duct obstruction?

A
  • Gall stones
  • Malignancies of the biliary tree or HEAD OF THE PANCREAS
  • Strictures from surgery
146
Q

What are the surgical treatments for jaundice caused by cholestasis?

A

Intrahepatic: Transplant ONLY

Extrahepatic: Surgical correction to reverse obstruction (prevent billiard cirrhosis)

147
Q

Ascending Cholangitis:
Describe the condition and clinical manifestations.
What is one morphological obstruction that can lead to this disease?

A

Intermittent instruction of canalliculi or duct (ball in valve, stricture, etc)–> secondary bacterial infection (enterococci from gut) –> fever, chills, URQ pain, jaundice

148
Q

What is suppurative cholangitis?

A

This is really bad ascending cholangitis with pus in the bile ducts –> may cause SEPSIS

149
Q

Which organisms are most likely to cause sepsis associated cholestasis?
What are the two types of sepsis associated cholestsiasis?
Which is associated with septic shock?

A

Gram (-) organisms–> this is cholestasis SECONDARY to septicemia

  • Canalicular cholestasis
  • Ductular cholestasis Septic shock (Duck when you’re in shock!)
150
Q

Three important histo findings associated with canalicular cholestasis:

A
  • Centrilobular canalicular BILE PLUGS
  • KUPFFER CELL ACTIVATION
  • MILD PORTAL INFLAMMATION
151
Q

Two important findings associated with ductular cholestasis:

A
  • dilated canals of hiring + bile ductules
  • bile plugs
  • *Worse pathologically than canalicular cholestasis
  • *Assocated with septic SHOCK
152
Q

What defines neonatal cholestasis?

What are two potential causes of this disease?

A
  • CONJUGATED hyperbilirubinemia w jaundice LONGER than 14-21 days
  • Associated with neonatal hepatitis and cholangiopathies (biliary atresia)
153
Q

Neonatal hepatitis:

What are the 4 etiologies? Describe what happens.

A

Metabolic, toxic, infectious, idiopathic–> injury to immature bile secretion and synth pways–> decompensation + hepatitis

154
Q

How many cases of neonatal hepatitis require a biopsy to diagnose? What will you see on the biopsy (4)?

A

Most diagnosised clinically (wo biopsy)

Histo:

  • GIANT CELL TRANSFORMATION
  • Necrosis w/ neutros
  • apoptotic acidophilic bodies
  • extra medullary hematopoiesis
155
Q

Describe giant cell transformation; which which type of hepatitis is it associated?

A

Unique response of young lifer to injury in NEONATAL hepatitis

Mitotic inhibition + dissolution cell membranes–> giant cells

156
Q

What is biliary atresia?

How does it present in the little babies?

A

Complete/ partial obstruction of EXTRAHEPATIC biliary tree in 1st 3 mos

  • 30% all neonatal cholestatic cases
  • Asx w. jaundice, dark urine, pale stool
157
Q

What are the two etiologies of biliary atresia and which is most common?

A

1) Fetal/ embryonal- intrauterine development problem (asstd. w other situs inverts, etc)
* *MC**

2) Perinatal- asstd. with insult @ birth i.e. viral infection

158
Q

What are the histopathological changes associated with biliary atresia? (3)

A
  • inflammation–> fibrosis + strictures in hepatic/ common bile duct
  • enlarged, dark green liver
  • micro nodular cirrhosis
159
Q

What are the two treatments for biliary atresia?

A

Surgery (Kasai procedure bypasses atretic ducts) or transplant

160
Q

What is the difference between primary and secondary hemochromatosis?

A

Primary:
(AR) HFE gene mutation–> Fe overload

Secondary: 
Known insult (^ transfusions, ineffective erythropoiesis, excess intake)--> Fe overload
161
Q

What is HFE hemochromatosis?

What is the genetic mutation involved?

A 
Chrom 6 C282Y mutation on HFE gene (cystine--> tyrosine)--> 
Hepcidin deficiency (Liver Fe hormone)--> 
^ Fe absorption of intestinal Fe --> 
^ Fe released into bloodstream, deposited in tissues
162
Q

How much storage Fe must be accumulated before deposition in parenchymal tissues takes place during hemochromatosis?

A

20g

163
Q

What is the clinical triad associated with hereditary hemochromatosis?

A

Triad (May develop late):

  • Micronodular cirrhosis (HM)
  • DM (pancreatic damage)
  • Bronze/ slate gray pigment of skin (^ melanin)

Also:

  • dilated cardiomyopathy + arrhythmia,
  • pituitary/ adrenal/ thyroid/ parathyroid
  • joints (pseudo gout)
164
Q

How is Hereditary hemochromatosis diagnosed w liver biopsy (2)? How else?

A
  • Stainable Fe in periportal hepatocytes w prussian blue
  • hepatic iron index (HII) +/= 1.9
  • genetic testing is confirmatory

**Should also check serum Fe, ferritin, total fe binding capacity

165
Q

What are the two most common causes of death for patients with Hereditary hemochromatosis?
For which cancer are they at increased risk?

A

Cirrhosis, Heart failure = most common causes of death

^ risk HCC

166
Q

What is the typical treatment for patients with hereditary hemochromatosis?

A
  • repeated phlebotomy

- chelation w deferasirox, deferoxamine, oral deferiprone

167
Q

List come causes of secondary hemochromatosis (these may be intuitive, just read don’t memorize)

A
  • transfusions
  • thalassemia
  • ineffective EPOsis
  • chronic liver disease, cirrhosis’s
  • ^ Fe intake
168
Q

What is the mutation that causes wilson’s disease?

What happens as a result of this mutation?

A

(AR) ATP7B mutation Hepatocyte Cu-Transporting ATPase –>

Impaired Cu excretion into bile (not incorporated into ceruloplasmin)–>
Toxic levels of Cu in eye, brain, liver

169
Q

How does wilson’s disease present clinically? How do we diagnose it?

A

Clinical:

  • Liver changes resemble viral hepatitis + fatty change
  • Depression/ Bx changes
  • Asymmetrical tremor, ataxia, ^ salvation,
  • **KAISER FLEISCHER RINGS around IRIS **

Dx:

  • No genetic testing
  • Do liver biopsy (^^^ Cu)
  • Labs: ^ urinary Cu, LOW serum ceruloplasmin
170
Q

At what age does Wilson’s disease typically present; what implications does this have for accurate diagnosis?

A
  • presents in teens/ 20s with neuropsych sx.

- commonly misdiagnosed as schizophrenia

171
Q

Which parts of the brain does Wilson’s disease damage?

A
  • lenticular nucleus (basal ganglia)
172
Q

How do we treat wilson’s disease?

A

Cu chelation w penicillamine, trientine, oral zinc

173
Q

How does a-1 Antitrypsin Deficiency manifest in the liver?

What is the inheritance pattern + mutation that cause this disease?

A 
(AR) SERPINA1 mutation on chrom 14--> 
Deficient AAT (due to defective Pi migration from ER to golgi)--> 
Unrestricted protease activity in lung + accumulation of A1AT-Z in liver
**Liver has PAS (+) intracytoplasmic lesions
174
Q

What are the three genotypes associated with a-1AT Deficiency?

A

PiMM- wild type, normal
PiZZ- diseased
PiMZ- codominant intermediate

175
Q

What are the 3 clinical presentations associated with PiZZ genotype a-1 Antitrypsin deficiency patients?
Which cancer are these patients at increased risk of developing?

A
  • neonatal liver disease (hepatitis, cholestasis, fibrosis)
  • chronic hepatitis–> childhood/ adult cirrhosis
  • ^^ HCC
176
Q

What are the pathological changes that take place in a liver w/ a-1 ATD?

A

PAS-D (+) globules, +/- mallory bodies, steatosis

177
Q

Define primary biliary cirrhosis.

Who most commonly gets this disease?

A

Autoimmune attack of medium sized intrahepatic bile ducts–> chronic fatal cholicstatic liver disease

Most common in women; often co-presents with other autoimmune disease

178
Q

What are the clinical manifestations/ lab findings associated with primary biliary cirrhosis?

A
  • May be asx or present with biliary cirrhosis’s

- ^ ALP

179
Q

Describe the stages of Primary Biliary Cirrhosis (4):

A

Portal: Portal Inflammation, BD damage,
florid duct lesion

Peripheral: Periportal inflammation, ductular proliferation , fibrosis

Septal: Bridging fibrosis, ductopenia

Cirrhosis: Biliary cirrhosis

180
Q

Describe the Lab findings associated with primary biliary cirrhosis.
What is the autoAb associated with this disease?

A
  • ^ALP, ^ GGT

- ANTIMITOCHONDRIAL AbS*

181
Q

How do we treat primary biliary cirrhosis?

A

Treat with ursodiol or transplant in advanced disease

182
Q

What is secondary biliary cirrhosis?

A

Prolonged obstruction of EXTRAHEPATIC biliary tree–> fibrosis–> cirrhosis

183
Q

Define primary sclerosing cholangitis;

***With what disease does this commonly co-present?

A

Autoimmune disease–> Inflammation/ fibrosis –> obliterates intrahepatic + extra hepatic bile ducts up to ampulla of vater w/ DILATION (BEADING on Imaging) of preserved segments

COMMONLY COEXISTS WITH ULCERATIVE COLITIS
P-ANCA (+)

184
Q

Describe the histo-path and lab findings associated with primary sclerosing cholangitis:

What infiltrate is found in the stroma?
Describe the fibrotic changes.
What will we find in circulation?
On imaging?

A

Histo Path:

  • T cell infiltrate in stroma (Activated in GI tract–> X-rxn with bile ducts)
  • ONION SKINNING periductal fibrosis

Labs/ Imaging:

  • circulating auto-Abs, P-ANCA
  • BEADED appearance of dilated spared segments on imaging
185
Q

What are the clinical manifestations of primary scleroscing cholangitis?

A
  • Typical cholestatic symptoms (jaundice, puritis)
  • Persistent asx ^ ALP
  • Chronic liver disease
  • Encephalopathy
186
Q

What are the risks associated with primary sclerosisng cholangitis? (2 cancer, 2 other)

How do we treat this disease?

A
  • HCC , Cholangiosarcoma
  • Chronic Pancreatitis
  • Autoimmune pancreatitis w/ ^ IgG4

Treat with transplant; give cholestyramine for puritis

187
Q

Is the gallbladder necessary for biliary function?

A

No! It stores, concentrates and adds mucus to bile but obviously, due to the high incidence of cholecystectomy, patients can live without their gallbladders…

188
Q

Cholelithiasis: define the term?
How common is this??
Define the two types of cholelithiasis.

A
  • Gallstones! Accounts for 95% of biliary disease…

- Can be cholesterol stones or pigment stones

189
Q 
Where do we find cholesertol stones? 
What do they look like? 
What type of crystals do they have? 
Do they show up on imaging? 
What population gets a lot of these?
A
  • ONLY found in gallbladder; crystalline, glistening
  • Can be pure cholesterol or complexed with Ca carbonate, PO4, bilirubin
  • Pure cholesterol stones = radiolucent
  • Common in Native Americans
190
Q

How is cholesterol solubilized (2)?

Describe how/ when stones form?

A

Cholesterol + bile salts or lecithins–> Solubilized
via Aggregn

When concentration is supersaturated cholesterol binds monohydrate crystals–> becomes STONE!

191
Q

List 4 circumstances that can facilitate cholesterol stone formation:

A
  • supersaturation of bile w/ cholesterol
  • hypermobile gallbladder (dyskinesia)
  • accelerated cholesterol nucleation
  • hyper secretion of mucus (traps nucleated crystals in GB)
192
Q

Where are are pigment stones most common?

What causes pigment stones (3 disease states)–what are they composed of?

A
  • More common in nonwestern countries
  • Composed of unconjugated billirubin + insoluble Ca salts

Associated with three disease states:

  • chronic hemolysis
  • severe ileal dysfunction/ bypass
  • bacterial/ parasitic infection of biliary tree
193
Q

Which infections can cause the formation of pigmented stones (3)?
Is unconjugated bilirubin normal in bile?

A
  • E coli
  • Ascaris lumbricoides
  • Chlonorchis sinensis

Unconjugated bilirubin is normal in bile

194
Q

What is biliary colic?

Describe the sensation–what does it feel like, what two things make it worse?

A

Pain asstd with gall stone; note that they may be asx…

  • Constant, excruciating pain in RUQ +/- radiation to shoulder/ back
  • Worse with fatty meal
  • Increased as stone moves through GB outlet
195
Q

What is cholecystitis?

A

Inflammation of the gall bladder; may be associated with stones; painful

196
Q

What are 6 complications associated with gallstones?

A
  • empyema (pus)
  • perforation
  • fistula
  • obstructive cholestasis
  • cholangitis
  • pancreatitis
197
Q

What is the most common cause of acute cholecystitis?

This is the #1 cause of two things; what are they?

A
  • # 1 cause = stone obstructing neck/ cystic duct
  • # 1 impromptu complication asstd. with gall stones
  • # 1 reason for emergency cholecystectomy

**This can occur in severely ill patients without stones as well

198
Q

How do acalculus and calculus ACUTE cholecystitis differ in appearance?
What do we see grossly?
How does appearance differ b/w mild and severe cases?

A
  • No difference b/w calculus and calculus cholecystasis in gross appearance (excepts stones, obvious)

Gross appearance:

  • Serosa w fibrinous exudate
  • Lumen =cloudy bile (pus/ fibrin/blood), +/- stones
  • Empyema
  • Mild = thick, edematous, hyperemic wall
  • Severe = granuloma, perforation
199
Q

Describe the clinical presentation of acute cholecystitis:

A
  • RUQ, epigastric pain LONGER than 6 hrs
  • fever, tacky, sweating n/v
  • +/- jaundice (if common bile duct obstructed)
200
Q

Describe lab findings associated with acute cholecystitis (2)

How is it treated?

A

Labs: mildly ^ ALP, leukocytosis
Tx: sudden onset may be surgical emergency; may be mild sx that subside within 1 week

201
Q

How does one develop chronic cholecystitis?
90% are associated with what

How does it present clinically?

A
  • may or may not be associated with repeat acute attacks
  • 90% associated with stones

Clinical presentation more mild than acute’ n/v/ intolerance to fatty food

202
Q

Are there differences in histological appearance between calculus/ acalculous asstd. chronic cholecystitis?
What is the most likely cause?
1/3 asstd. with what pathogen?

A
  • no histo differences between calculus and calculus
  • likely due to long term stones + low grade chronic inflammation
  • 1/3 test (+) for e. coli
203
Q

What do we see path/ histo wise with chronic cholecystitis?

A
  • subserosal fibrosis
  • gray-white wall
  • green- yellow lumen w mucoid bile +/- stones
  • chronic inflammation w lymphoid follicles
  • Rokitansky- Aschoff sinuses (mucosa herniated into muscle layer)
204
Q

What causes the “porcelain gallbladder” associated with chronic cholecystitis?
What risks does this impose?

A
  • dystrophic calcification

- ^^ risk cancer

205
Q

List some of the complications associated with cholecystitis (acute OR chronic) (5)

A
  • Bacterial superinfection–> cholangitis/sepsis
  • GB Perforation–> abscess
  • GB Rupture–> peritonitis
  • GB/ enteric fistula–> gall stone ileus
  • Exacerbation of other medical conditions
206
Q

Describe the typical age and sex of a patient with cholelithiasis?
What medications may put patients at risk for cholelithiasis? (1)
What are some Hereditary/ acquired disorders that put patients at risk for cholelithiasis? (2)

A
  • Middle aged females= MC
  • OCPs–> ^ Estrogen–> ^HMG CoA Reductase activity –> ^ cholesterol stones
  • GB stasis, ^ # ATP transporters will ^^^ risk gall stones
207
Q

What are Von Meyenberg Complexes?

With what two hereditary diseases are they associated?

A

Hamartomas of ductal structures in hyalinized stroma within the biliary tree

  • PCKD
  • PCLD (isolated polycystic liver disease)
208
Q

What is one common finding associated with PCKD/ PCLD?

A

Congenital hepatic fibrosis

209
Q

Define Caroli’s disease and syndrome–what is the inheritance pattern?

A

(AR) Congenital, non-obstructive, segmental DILATION of intrahepatic bile ducts

  • isolated finding = disease
    • congenital hepatic fibrosis = syndrome
210
Q

Describe the clinical presentation of a patient with Caroli’s disease.

A
  • Late childhood/ early adulthood onset
  • recurrent fever/ pain/ jaundice
  • cholangitits sx. / labs
211
Q

Describe the histo changes associated with caroli disease (2); for what are these patients at ^ risk?

A
  • cholangitis w concretion + debris
  • sub capsular dilated bile ducts
  • ^ risk cholangiosarcoma
212
Q

Alagille Syndrome:
What is the inheritance pattern and associated mutation?

Describe the clinical presentation of this disease and what is seen on biopsy/ labs? (3)

A

(AD) Mutations in JAG1 –> low # of interlobular bile ducts

Patients present within 1st 5 yrs of life w/ chronic cholestasis, pruritis, xanthomas

Labs:

  • conjugated hyperbilirubimemia
  • ^ GGT, ^ ALP
  • hyperlipidemia
213
Q

Describe some of the sequelae associate with Alagille Syndrome.
What is the definitive treatment?

A
  • malabsorption of fat soluble vitamins etc leads to malnutrition asstd sequelae
  • peripheral pulm artery stenosis, vertebral arch defect, hyperbolic facies = other findings

Transplant is only treatment

214
Q

What are some of the causes of hepatic artery compromise and impaired blood flow into the liver? What are the sequelae?

A

Caused by arteritis, aneurysms, thrombi/emboli/ surgical ligation, occlusion of portal vein branch–>

Leads to coagulative necrosis, inflammation, hyperemic boarders (like all coag. necrosis infarcts)

215
Q

What is a hepatic infarct of Zahn? What are the sequelae

A

Acute thrombosis in small intrahepatic portal veins (impaired flow INTO liver)

Atrophy, hemostasis w/o necrosis

216
Q

What can cause impaired blood flow WITHIN the liver?

How will these phenomena present?

A

Cirrhosis–> Portal HTN, portal vein obstruction/ thrombosis

Presents with abdominal pain, esophageal varacies…

217
Q

Describe how blood flow is shunted during liver cirrhosis.

What are the 3 locations in which varicosities develop?

A

Portal venous system (^ pressure)–> collaterals–> IVC

  • Lower 1/3 esophagus
  • Umbilicus
  • Rectosigmoid
218
Q

What happens to the liver as a result of right sided cardiac decompensation?

A
  • Passive congestion of liver + centrilobular sinusoids

- Atrophy of liver cell plates

219
Q

What happens to the liver as a result of let sided cardiac decompensation?

A

Injury due to decreased perfusion:

  • centrilobular necrosis
  • ischemic coagulative necrosis
220
Q

What is Peliosis Hepatis?

How do they present?

A

Blood-filled cysts with incomplete endothelial lining form in the liber –typically asx, but can rupture or cause hepatic failure

221
Q

What are some potential causes of peliosis hepatis?

A
  • corticosteroids, anabolic steroids, OC, danazol
  • toxins, MTX, thorotrast
  • bartonella henselae, AIDS
  • hairy cell leukemia
222
Q

What is Budd Chirari Syndrome!?

How does it present?

A

Blood can’t LEAVE liver!

Thrombosis of 2+ major hepatic veins (western) or IVC (developing countries) –> blocked outflow tract–> ^ intrahepatic pressure

Presents with HSM, pain, ascites, ankle edema

223
Q

What are some of the potential causes or Budd Chirari Syndrome?

How do we treat it?

A

Caused by ^ tendency to coagulation:
OCPs, myeloprolif. disorders, coagulopahties, preggos…

Treat with anticoag / thrombolytics, angioplasty, TIPS + treat varicies

224
Q

Wha happens in sinusoidal obstruction syndrome?

A 
Toxic injury (i.e. ^ dose chemo) to liver--> 
sloughing of vascular endothelium--> obstruction of sinusoidal blood flow--> proliferation of perisinusoidal stellate cells/ fibrin + ECM deposition--> 
fibrotic occlusion of small hepatic vv's --> FATAL
225
Q

What are some of the potential causes of sinusoidal obstruction syndrome?

Do we biopsy this?

A

Herbal tea, pyrrolizidine alkaloids, chemo agents, BM transplant

Do not biopsy this; clinical dx.

226
Q

How do we treat sinusoidal obstruction syndrome?

A

Admin anticoag and control fibrin deposition with TPA, etc. –still fatal 50% of the time

227
Q

What are the two tumor like lesions that occur in the liver?

A
  • focal nodular hyperplasia

- nodular regenerative hyperplasia

228
Q

What is focal nodular hyperplasia and in wha population does it typically arise?

A

Vascular malformation of AV anastomoses w localized overgrowth of liver components

Typically 20-40yo woman; may be asstd. with OCPs

229
Q

What do we see (gross) pathologically its focal nodular hyperplasia?

A
  • UNDER 5cm

- well circumscribed; central stellate scar w blood vessels

230
Q

What is nodular regenerative hyperplasia?
With what is it associated clinically?
What are the asstd. lab findings?

A

Heterogenous microcirculation: Obliteration of small portal vv’s + arterialization–>
Liver full of multiple small nodules WITHOUT fibrous septae between

Clinically associated with many AI disorders + PV, CGD, etc.

Will see mildly ^ ALP + GGT

231
Q

What is a hepatocellular adenoma? What do they look like?
In which population do these tumors most commonly occur?
With what are they associated?

A

Benign tumor of hepatocyte; well circumscribed, pale yellow-tan sheets/ cords of NORMAL liver cells (can occur in mult.)

  • MC in young women on OCPS
  • Also men on androgen tx.
232
Q

What are two risks asstd with hepatocellular adenomas?

A
  • rupture during preggos

- transformation into HCC (MC in glycogen storage disease)

233
Q

What is the most common benign tumor of the liver?

Describe its characteristics

A

Cavernous hemangioma

  • Discrete sub capsular blue-red, soft, vascular lesion UNDER 2 cm
  • B/w 2 communicating dilated vascular spaces
234
Q

In which patient population do cavernous hemangiomas typically occur?
What are the clinical manifestations?

A

Middle aged females; typically incidental finding but may present with abdominal pain or spontaneous rupture (both rare)

235
Q

What is Kasabach Merritt syndrome?
With which tumor is this syndrome associated?
How is it diagnosed?

A

Associated with cavernous hemangioma; dx w imaging

  • Microangiopathic anemia
  • Consumption coagulopathy
  • Erythrocytosis (due to ^ EPO)
236
Q

What is the most common primary liver tumor in adults?
Describe the nature of this tumor.
With what is this tumor commonly associated?

A

HCC

  • Malignant tumor of hepatocytes
  • Commonly asstd with cirrhosis
237
Q

Where is HCC most common?

A

More common in developing areas (asia, africa, etc.) where HBV, HCV are high

238
Q

Review 6 predisposing factors to HCC.

A
  • alcoholic/ nonalcoholic cirrhosis
  • hemochromatosis
  • PBC; AIH; Aflatoxin
  • obesity related fatty liver disease
239
Q

How does HCC clinically manifest?

What are the asstd. lab findings?

A
  • Typical cancer shit + RUQ pain/ cirrhosis (follows after 10 yrs of cirrhosis)
  • Labs: ^ AFP**, ^ AST, etc.
240
Q

What would we expect to see on a liver biopsy w/ HCC?

A
  • pale, +/- green infiltrative mass
  • vascular invasion (intrahepatic mets)
  • may be well differentiated, anapestic, or fibrolamellar
241
Q

Describe the fibrolamellar variant of HCC.

In which population does it typically occur? How does it arise? How do we treat it?

A

Well defined nodule in NON-CIRRHOTIC liver; see large eosinophilic cells with fibrolamellar stroma

Typically occurs in 20-40 yo adults without hx of cirrhosis or liver disease; has better prognosis than regular HCC

Treat with surgical resection

242
Q

What is cholangiocarcinoma?
What are the risk factors and clinical manifestations?
What is the serum marker???

A 
#2 primary hepatic malignancy 
- Arises from ducts within/ outside the liver
  • Asstd. with PSC, gallstones, inflammation/ fluke infection, thorocrast/ chemicals, cysts
  • Dx typically late; difficult to dx
  • ^ Serum CA 19-9
243
Q

What is a klatskin tumor?

A

Cholangiocarcinoma arising in liver hilum–> leads to biliary obstruction

244
Q

Hepatic angiosarcoma; define the tumor

How is it treated?

A

1 primary sarcoma of the liver; arises from vasculature

Treat with whipple surgery or transplant

245
Q

Hepatoblastoma define the tumor and the population in which it most commonly occurs:
What are the 4 types?
With what syndromes are these tumors associated?

A

1 primary hepatic malignancy of childhood (^^ within 2yoa)

  • Epithelial (best prog)
  • Mixed epi/ mesenchymal
  • Anapestic

Asstd with Beckwith Wiedemann syndrome, Familial adenomatous polyposis

246
Q

What are the serum markers associated with hepatoblastoma?

A
  • ^ AFP

* *Low to normal AFP = MORE AGGRESSIVE

247
Q

What is one potential predisposing factor to developing hepatoblastoma?

A

Drugs used to maintain LBW babies

248
Q

What is more common in the liver: mets or primary hepatic tumors?

A

Mets! via hematologic, lymphatic, peritoneal spread–may be single or mult. lesions; depends on primary malignant

Smaller reasons may be asx.

249
Q

What is the most common metastatic tumor in adults?

What are three most common mets to the liver in kids

A

Adults: #1 = pancreatic; also colon, breast, lung

Kiddos: neuroblastoma, wilms, rhabdomyosarcoma

250
Q

What is the most common causes of jaundice in preggos?

A

Viral hepatitis; disease course not affected by preggos except HEV

251
Q

The disease course of which hepatitis virus is affected by preggos?

A

HEV; fatal in up to 20% preggos!

252
Q

What are the liver lab findings associated with pre-eclampsia?

How about liver biopsy?

A
  • ^ aminotransferases
  • ^ ALP
  • ^ bilirubin
  • coagulopathy = more severe, fatal

Biopsy shows periportal sinusoidal fibrin deposition and coagulative necrosis

253
Q

What is one possible dangerous hepatic outcome asstd with preeclampsia?

A

Sub capsular hematoma may dissect under gleeson’s capsule–> DEATH, bleed out!!!

254
Q

What does HELLP Syndrome stand for?

When does it occur and what do we see on lab findings and biopsy?

A

Hemolysis, Elevated Liver enzymes, Low Platelets–3rd trimester preggos

See hemolysis, ^ billy, ^ transaminases, Thrombocytopenia

Biopsy shows fibrin in periportal sinusoids + hemorrhaging in space of diss

255
Q

Acute Fatty liver or preggos:
When does this occur and what causes it?
With what may it be comorbid?
How is it treated?

A

Occurs in 3rd trimester
AR gene mutations–> Defective mitochondrial B oxidation–> ^ fat within hepatocytes; may lead to liver failure, death

Possibly asstd with preeclampsia
Delivery of fetus = only treatment

256
Q

What do we see pathologically with fatty liver of preggos?

A

Microvascular steatosis, scant inflammation necrosis

257
Q 
Intrahepatic cholestasis of pregnancy: 
When does this occur? 
Which type of preggos are at risk? 
How does it present? 
What are the associated labs?
A
  • third trimester in multiparous women w hx of cholestasis + OCP use
  • Patient have Pruritis, dark urine, light stools, jaundice
  • Labs: ^ conjugated billy, ^ ALP, VERY HIGH BILE SALTS***
258
Q

Describe the histopath findings associated with intrahepatic cholestasis of preggos:

A
  • centrilobular cholestasis w/ bile plugs in hepatocytes + canalliculi
  • scant inflammation
259
Q

What CAUSES intrahepatic cholescystasis of preggos?

A

Mutant phospholipid translocator (ATP cassete B4)–>

Defective biliary secretion of bile salts + sulfonated progesterone metabolites

260
Q

List 3 preggos complications that can occur with intrahepatic cholestasis of preggos

A
  • fetal distress
  • still birth
  • premature labor

DT4- Exam 3 (14 decks)

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