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MOD (liver stuff) Flashcards

1
Q

Zones of the liver list

A 
1 periportal (closest to vascular supply)
2 intermediate
3 centrilobular (closest to hepatic venule)
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2
Q

The diseases that first affect each liver zone?

A

Zone 1 periportal- viral hepatitis
Zone 2 intermediate- yellow fever
Zone 3 centrilobular- alcoholic hepatitis, ischemia, affected by toxins, contains cyto P450 sys

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3
Q

Kupffer cells and Ito cells

A

Kuppfer—liver macrophages that line sinusoids

Stellate (Ito) cells—in space of disse, store vitamin A at rest and produce ECM when active, produce fibrosis

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4
Q

Portal triad

A

HEPATIC artery
PORTAL vein
COMMON bile duct

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5
Q

When do ascites occur in liver

A

When there’s portal HTN and lymph fluid accum (liver is largest producer of lymph) in peritoneum, lymph is produced in space of disse and travels around and drains

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6
Q

Common metabolic causes of liver injury

A
  • Hemochromatosis—genetics cause excessive iron absorption from intestines, which accum in liver
  • A1AT deficiency—causes unopposed protease dmg
  • Wilson’s disease—defect in copper secretion from liver causes it to accum (will be in urine too)
  • GSDs and dev abnormalities like biliary atresia
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7
Q

Viral causes of liver injury

A

Hepatitis A (acute), B (chronic in Asians), C (most common cause of chronic and cirrhosis), herpes, adeno

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8
Q

Drug causes of liver injury

A

Adverse rxn to acetaminophen (Tylenol) causes half of liver injuries in US

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9
Q

Other causes of liver injury

A

-toxins like alc and vinyl chloride, vascular insults like thrombosis etc

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10
Q

Causes of acute vs chronic liver injury

A

Acute is hep A, whereas chronic (more common, can lead to fibr/cirr) is hep B/C (also autoimm, met/dev dis)

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11
Q

Which enzymes indicate liver injury vs biliary tree dmg?

A

ALT/AST is liver, GGTP and ALP are biliary tree (canaliculi enzymes)

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12
Q

Other test signs of liver damage vs biliary

A
  • AMA elev is dx for Primary Biliary Cirrhosis (and other autoimm ab’s like ANA etc, for liver measure ferritin (dx hemochromatosis or secondary hemosiderosis), copper to dx wilson’s
  • Liver dmage can involve coagulopathies (since liver cells make coag factors) and hypoalbuminemia (if chronic liver failure)
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13
Q

Hepatocellular histo changes in liver injury:

A
  • dead hepatocyte necrosis/apoptosis which are acidophilic
  • ballooning degen (enlarged liver cells) seen in NASH (non alc steat hep)
  • mallory’s hyaline bodies—dmgd intermediate filaments in liver cells (chronic hepatitis)
  • ground glass hepatocytes (HBV)
  • atrophy (small liver cells)-vasc insuff or elderly
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14
Q

Intercell accum in liver injury

A
  • A1AT globules
  • lipid accum (steatosis)—large white round fat globules (macrovesicular steatosis pushes nuclei to periph)
  • MPS, glycogen
  • pigments: Iron (hemochrom/hemosiderin pigment), dubin-johnson syndrome (incr of conj bili in serum causes black liver, presents as jaundice), lipofuscin (wear and tear pigment), bile (cholestasis—bile can’t flow out of liver), copper (wilson’s disease)
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15
Q

acute vs chronic inflamm of liver

A

acute—short duration, hep A

chronic—fibrosing (instead of regen like in acute), Hep C mostly (also Hep B and Hep D), other

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16
Q

What can happen in fibrosis/ pathology?

A

From chronic injury, alc/NASH/ischemia, venous outflow obstruction (budd-bhiari syndrome is occlusion of hep veins), CHF, veno-occlusive disease, also from portal fibrosis (biliary or hepatitis)

  • end stage fibrosis is cirrhosis (regen nodules encircled by fibrosis, can’t see central vein, parenchymal architecture disrupted)
  • portal HTN
  • decompensated cirrhosis can lead to ascites, hemorrhage, hep enceph, coagulopathy etc
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17
Q

Portal hypertension pathology

A 
Involves ascites in peritoneum
Portosys shunts (gut, but and caput)—esoph varices, caput medusa, hemorrhoids, splenomegaly, hepatic enceph from increased ammonia, coagulopathy from decr liver prod of clotting factors
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18
Q 
Non-Alcoholic fatty lvier disease (NAFLD)
Cause
Dx
Histo 
Stages
A

Cause: high cals + sedentary lifestyle, obesity, DM
Dx: neg alc history, fatty liver presence on liver biopsy (Gold std), imaging
Histo: hepatocell injury (ballooning/necro/apop/mallorys hyaline), inflame (neutros lymphos macros), fibrosis

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19
Q

Stages of lesions in NAFLD

A

normal, fatty change, steatohep/fibrosis, cirrohosis, hepatocellular carcinoma

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20
Q 
Histo slides:
Mallorys hyaline (alc liver dis)
Hemochromatosis 
Councilman/acidiphilic/apoptotic bodies (in acute injury)
Cholestasis 
Liver cirrhosis
A

Mallorys—pink stuff, usu in alc liver disease
Hemochrom—Accum of hemosiderin pigment in liver cells
Pink cytoplasm in cells
Cholestasis—greenish bile accum
Regen pink nodules (round circles) completely encircled by fibrous bands (blue)

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21
Q

6 types of cirrhosis/causes?

A 
Alcoholic cirrhosis 
Cirr secondary to hemochromatosis 
Secondary to wilson’s disease
Secondary to A1AT deficiency 
Biliary cirr 
Cirrhosis NOS (not otherwise specified)
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22
Q

Bile flow vs blood flow, and drainage of blood path

A

Blood flows from A/V into central vein (???), bile flows in opposite direction
Blood from spleen etc flow into portal vein to liver to sinusoids between liver cells to IVC to heart

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23
Q

Chronic heptatitis
Def
Staging
Dx

A

Diffuse necroinflammatory and fibrosing liver disease> 6 mo
Staging is amt of fibrosis—portal, 0 is no fibrosis and stage 4 is cirrhosis
Labs—prolonged INR (due to less clotting factors made so can’t clot as fast), elev bili (mainly conj or mix), low alb, thrombocytopenia (less than 150k platelets), thrombopoeitin, mild pancytopenia, high ferritin

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24
Q

Portal hypertension

A
  • Increase in bp in portal venous system (veins that merge with portal vein and travel into liver), often due to scarring/remodeling (cirrhosis) increasing flow resistance
  • increase pressure can cause collateral flow (reversal of flow from gastric to splenic v, causing splenomegaly), goes thru esoph and causes esoph varices, can also happen in rectum leading to hemorrhoids
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25
Leading cause of death for chronic liver disease?
Rupture and hemorrhage of gastric and esoph varices
26
Ascites and how are they measured?
Increased lymp prod from liver Serum ascities albumen gradient (SAAG) is serum albumin-ascites albumin), if it’s >1.1 this means portal HTN (an excess fluid would have lower alb than serum would), distends stomach -low protein levels in ascites fluid occurs bc scarring causes fenestrations in endoth to become smaller so RBCs can cross but not prots
27
Hepatorenal syndrome
Involves liver, circ sys and kidney - compensated cirrhosis rel NO which vasodilates arteries and incr blood vol (thus can look normal), travels to fibrotic liver, heart senses underperfusion which activates baro reflex incr EF and CO, increased RAAS - decomp: worsening vasodil til heart cant compensate, causes sys pressure dicr and ascites, chronic renal insuff due to low perf, renal aa vasoconstrict causing renal failure
28
Hepatic encephalopathy (path, sx, tx)
- due to excess ammonia - colon conv bacteria into ammonia which is converted by liver to glutamine for storage in muscle or excretion in kidney - in cirrhotic liver ammonia accumulates (if coexisting renal failure and loss of muscle mass then excess ammonia goes to brain) - sx: sleeping trouble, asterixis, memory, etc; skin changes (incr estrogen and gynecomastia), palm erythema, spider angiomas from shunts - tx: lactulose (acidifies ammonia into ammonium which can’t get to brain), purged from colon)
29
Sx of gynecomastia, muscle wasting, distended abdomen with ascites, jaundice, varices from portal HTN, musky smell on breath can mean…?
Cirrhosis!
30
``` Alcoholic hepatitis Sx Labs Imaging Histo ```
- sx: febrile, jaundice, muscle wasting, nausea, RUQ pain, look septic with incr WBCs - labs: AST/ALT (high INR???), negative for ab’s stuff, ferritin etc - imaging: hepatomegaly, ascites, etc etc - histo: fat droplets, Mallory bodies (pink) (cx), chiken wire fibrosis in liver
31
Diff types of alc liver diseases (spectrum)
Fatty liver, Alc hepatitis, cirrhosis, micronodular cirrhosis
32
``` Wilson’s disease Genetics Sx Labs Histo Dx ```
Genetics: AR met defect in ATP7B reducing copper excretion in bile, causes accum of copper in bile Sx: usual, looks like hep/cirrhosis Labs: anemia /schistiocytes (low hb), ceruloplasmin low, urine copper high Histo: vacuolated hep nucle, macrovesicular steat, Mallory bodies (but non spec) Dx: get biopsy and do copper stain for wilsons (elev)
33
``` A1AT storage disease Genetics Hepatic manifestations Tx Histo ```
Genetics: AR disorder causing low A1AT levels (protease inhibitor), accum in liver cells and imparie degradation, causing inflame in liver and fibrosis/cirr, can be emphysema also - hepatic: neonatal hep with cholestasis, hep in adolescence, or silent until cirr - tx: liver transplants - histo: PAS positive globules within liver cells
34
``` Hemochromatosis Path Genetics Pop Sx ```
Path—accumulation of body iron which deposits in liver and other organs - genetics; AR mutation of HFE (C282Y) gene with missing/defective hepcidin that incr intestinal abs of iron (diff from secondary iron overload from sickle cell or transfusion etc) - pop: men after 40 yr, northern Europeans - sx: no inflame, classic traid of cirr and skin pigment and diabetes
35
All the above diseases can cause cirrhosis. What can cirrhosis lead to?
Portal hypertension!
36
Acute liver failure (as opposed to chronic), cause, tx
Rapid liver cell death that occurs too fast for scarring, coagulopathies (elev INR), jaundice, enceph occur within weeks - tx: need immediate transplant bc medical emergency! - can be caused by mostly HBV, or hsv/meds(acetaminophen), autimm, death cap mushrooms etc
37
Acute hepatitis Def Histo Causes
Less than 6 months Histo--lobular and portal inflam/necrosis Causes: viruses (hep), usu HCV, and other viruses, also acetomin (but lacks sero markers for hep), alc, vasc, misc diseases like wilsons
38
Fulminant Hepatitis
Necrosis of liver parenchyma causing acute liver failure and high mort
39
Chronic viral hep Def Histo
More than 6 mo Histo shows inflam with necrosis usu around zone 1 periportal (zone 2 is lobular), fibrosis which may lead to cirrhosis (we STAGE fibrosis, and GRADE inflam)
40
chronic vs acute liver inflam histo
chronic-lymphos around portal tracts (z 1) | -acute--lobular inflam (z 2)
41
Histo of stages 1-6 of fibrosis
Stage 1--blue tissue collagen, limited fibrosis to portal tract stage 2--enlarged portal area, pseudopods of fibrosis extend to pernchyma stage 3--needle biopsy stage 4+ fibrosis and cirrhosis
42
``` What can sx of: elev AST/ALT that then decr Alk phos Pos anti-HAV total bili ferritin elev incr PT time high reat hypogly agitation mean with regards to Hep A? Tx? ```
From fulminant hepatitis caused by Hep A! ALT and AST rel from cell death then liver stops producing it and it decr, alk phos incr from bile duct obstr, bili means lvier disorder, elev ferritin means inflammation (acute phase rct)m, PT time incr meaning decline in clotting factor liver fxn, high creat means liver failure, hypoglycemia means impaired liver gluconeo, agitation from hepatic enceph -Tx: liver transplant
43
Hepatitis A virus type? transmission? complications?
small ssRNA virus from PICORNAVIRUS family self limited and mild USUALLY fecal-oral transmission (close contacts, food contamination like raw oysters, homeless etc)
44
What is the serology in hep A?
IgM means acute | IgG means chronic or past
45
What does it mean when HBsAg and anti HbE are positive but HbeAg is negative?
past infection but not current | positive HBeAg may mean HBV infxn was reactivated
46
High alpha-fetaprotein levels may mean
hepatocell carcinoma, tx w RF ablation, liver transplant
47
Hep B virus type risk factors geog
part dsDNA virus (Hepadna) risks is IVDU, msm, occupational w needles, etc highest in africa asia and s america, immigrants
48
Dx markers for acute Hep B infxn
HBSAg | anti-HBc, IgM
49
what can hep B result in in most neonates
chronic liver infxn if acquired at birth, risk of HCC or chronic liver disease but most adults clear the infxn can reactivate under immunosupp
50
prophylaxis for acute hep B
HBIG ab's for short term, and vaccine | all pregnant women screened, give antiviral tx in trimester 3 if positive
51
Sero.logy for chronic hep B infxn
HbeAg early on only, ALT, liver dis
52
Nucleotide analogs for HBV therapy (suppress but dont clear)
Entecavir, Tenofavir, also lamivudine and others, and INF-a
53
Hep D virus type geog histo
RNA virus that req HBV for repl can have co infxn with B and D, can dev from mild to fulm hep -superinfxn is hep B prev and now hep D -africa, middle east, italy -HDAg in hep nuclei, microvesicular steatosis (small fat vacuoles in cytoplasm)
54
Hep E genotype facts
1/2- never chornic unless immunocomp, pregnant women can get acute liver failure/death -3/4 can be zoonotic (pigs)
55
``` Hep C virus type common genotypes in US and world distr px typical transm risk factor for? results/compl dx histo ```
ssRNA virus (hepacivirus), 6 genos - most common chron bloodborne infxn, causes liver dis - US most common genotype is 1, ww is 4 - has bimodal distr, baby boomers had it and opoiod epidemic - unlike hep B, most adults with Hep C dev chronic inf - risk factor for HCC and cirrhosis - transmission usu IVDU and others - compl: lympho, neurop, MPGN, depr, CV, type 2 DM etc - can dx with fibroscan - histo: lymphoid follicle, inflam cells, dmg bile duct, steat
56
What might decompensated liver cirrhosis have
ascites, esoph varices, enceph (less than 2 yr survival, whereas if compensated can be over 12 yr)
57
HCV tx
treat with two drugs bc high mutation rates and can dev res | -8-12 wk
58
which is the only virus that DOESNT cause acute liver failure
Hep C! (other heps and hsv do) | aceto, vasc, and wilsons etc also do
59
which hep is acute only?
hep A!
60
which hep has high risk for acute liver failure/death in preg women?
hep E
61
which hep will give neonates chornic infxn but clear for adults?
hep B
62
which hep is mostly chronic
hep C
63
which hep can have co-inf and superinf
hep D
64
which hep needs HBV to survive
hep D
65
which hep has microvesic steat on histo
hep D
66
which one can you get from shellfish
hep A

T2 GI (6 decks)

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