Term
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Definition
Present in BOTH cytosol and mitochondria
If in serum, reflective of hepatic cell death
If double ALT, consider alcoholic hepatitis |
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Term
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Definition
| Located in the CYTOSOL, reflects rearrangement of that cellular zone |
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Term
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Definition
Alkaline phosphatase and gamma glutamyl transferase
located in cnalicular (ductal) tract through gall bladder, panc duct, and common fuct.
Elevation of both enzymes reflects obstructive lesions in the biliary tract |
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Term
The liver is the maiin source of most protein synthesis -- Albumin
alpha 1
alpha 2
Beta globulins
fibrinogen
prothrombin
Name on major that IS NOT made in liver |
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Definition
Gamma Globulins
Made in B lymphocytes |
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Term
| Discuss removal of Bilirubin from |
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Definition
| 1- Globin Chains are detached and recycled (green pigmented BILIVERDIN is seen in severe hepatic DZ) Reducing step --> Bilirubin Bilirubin is toxic - attaches to ALBUMIN A (2B to 1 A) **INSOLUBLE** Circulates through vasc channels of liver, INSOLUBLE At sinusioid, dissocociates from albumin, and FREE BILIRUBIN moves accross memb into cell, IMMEDIATELY complexes with intracellular protein, conveyed to ribosome NOW>>Binds to gluconuride in liver cells, making it CONJUGATED (AKA DIRECT), and SOLUBLE In healthy individual, most passes into the canaliculus If the passage into the canaliculus is impeded, it will recurculate in blood THIS IS CALLED DIRECT (CONJUGATED/SOLUBLE) BILIRUBIN If this re,ains in high conc., will convert to DELTA bilirubin, indicating hepato biliary stasis In a healthy individual, the direct bilirubin is carries to small intestine, converted to STERCOBILINOGEN, which is carried to feces Some stercobilinogen is absorbed by small intestine, and called UROBILINOGEN, which is excreted in urine |
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Term
| what are the two test (Urine and Fecal) to test for propper Bilirubin conjugation and excretion |
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Definition
Stercobilinogen -- Conjugated (Soluble and bound to glucuronide) passes through large intestine
Urobilinogen - urine -- Stercobilinogen that is reabsorded in SI, and excreted by kidney |
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Term
Cringler-Najjar Syndrome
1) Type 1
2) Type 2 |
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Definition
1)
Complete lack of enzyme UDP-Glucuronyl transferase
No Conjugation to dirrect, gluconuryl bound bilirubin
100% unconjugated/indirect
FATAL
2)
Partial defect |
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Term
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Definition
Benign dz
Reduced UDP-Gluconuryl transferase |
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Term
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Definition
Limited syndromes, pigmented liver
Defective transport protein resp for hepatocellular excretion of Bilirubin glucuronides across canalicular membranes.
NO UROBILINOGEN |
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Term
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Definition
Asymptomatic -- NO PIGMENTATION of liver
SAME AS DUBIN-JOHNSON, but NO Pig
defect in TP protein resp for helatocellular excretion of Bilirubin gluconides
No Urobilinogen |
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Term
| Which liver syndrome can be fatal? |
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Definition
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Term
| Kernicterus is caused by: |
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Definition
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Term
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Definition
Benighn syndrome with reduced UDP-Gluconyl transferase
Change in diet may result in MINIMAL direct bilirubin |
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Term
| What is the anatomic defintion of a cirrhotic liver? |
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Definition
| Replacement of lobar architecture by nodular architecture |
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Term
| ****Vasculitis is not a consequence of portal hypertension from cirrhosis*** |
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Definition
| ****Vasculitis is not a consequence of portal hypertension from cirrhosis*** |
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Term
Hepatic Steatosis:
Two kinds: Macrovesicular and Microvesicular (3 ex) |
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Definition
Steatosis = accumulation of fat droplets within hepatocytes
Macro: Fat puched nucleus to side
More common -- less specici
Diabetic
obses
alch liver
Micro: Centrally placed nuc.
More specific
Reye's syndrome
Acute fatty liver of pregnancy
alch liver |
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Term
| Where are progenitor cells for hepatocytes and bile duct cells found? |
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Definition
Canals of herring
known as OVAL CELLS -- prolif when hepatocytes are unable to replicate |
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Term
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Definition
| With progressive parenchymal inj and fibrosis, the liver develops NODULESof regenerating hepatocytes surrounded by bands of SCAR TISSUE |
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Term
| Hepatic failure = ___ % loss of liver func |
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Definition
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Term
| 2 consequences that result from Hyperestrogenemia as a result of liver failure: |
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Definition
Spider angiomas
palmar erythema (reflection of vasodialation)
in males, also lkeads to hypogonadism and gynecomastia |
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Term
Hepatic Encephalopathy
test/sign |
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Definition
Liver failure and loss of hepatic cellular func = shunting of blood from portal system around chronically dzed liver
--> INC in Ammonia, which impairs neurological function and promotes generalized BRAIN EDEMA
-->fluct in neuro signs -- rigididty, hyper-redlexia, nonspec changes, seizure
ASTERIXIX = flapping tremor when trying to dorsiflex wrist |
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Term
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Definition
Splanchnic Vasodialation
&
Systemic Vasoconstriction
--> severe renal blood flow retention to the CORTEX
dec in urine output, increase in BUN and creatinine
***The ability to conc urine is retained, so HYPEROSMOLAR urrine divoid of protein and low sodium |
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Term
| Normal liver collagen structure vs cirrhosis |
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Definition
Normal -- 1, 3, 5, 9 present only in capsule, portal tract, and central vein.
there is no true basement memb. only delicate network of type 4 around hepatocytes and endothelial cells
type 1 and 3 are only in portal tract
ABN:
types 1 and 3 diposite in space od DISSE
type 1 and 3 in all portions of lobule (In NORMAL, 1 and 3 are only in Hepatic tract)
in advanced, the fibers sparate nodules of hepatocytes and develope shunts @ liver |
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Term
| what does the amt of cell layers tell you about liver? |
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Definition
normal - 1 cell this
cirrhosis - 2 cells this
3 and above - malig., carcinoma |
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Term
| Renal Failure with NO intrinsic cause is characteristic of _____ |
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Definition
Hepatorenal failure
Increased BUN and CR |
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Term
| T/f - Fibrosis in cirrhosis is irreversible |
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Definition
true
Vasc structure is reorganized |
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Term
| Which Hepatitis has the largest potential to cause epidemic? |
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Definition
Hep A - pecornavirus
Contagious, but Self-Limiting, rarely causing chronic or fulminant hep
Dmg caused by t cells
Detected by IGG |
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Term
| What is an imp pecursor for the development of hepatocellular carcinoma? |
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Definition
Hep B
Hepadenovirus (DNA)
Immune for life. |
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Term
____ = transmitted by blood mainly
--Very high rate of progression to chronic dz, and cirrhosis
***This with alch = most common causes of Cirrhosis in us**** |
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Definition
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Term
| Which hep is a calcivirus? |
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Definition
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Term
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Definition
|
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Term
| Reasons for predominantly conjugated bilirubin: |
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Definition
bILIARY OBSTRUCTION
Extrahepatic
Intrahepatic
Dubin-Johnsons Syndrome
Pigment in liver
Rotor Syndrome
No pigment in liver |
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Term
| Name a drug that gives an idiosyncratic reaction: |
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Definition
- Chlorpromazine sulfamines methyldopa allopuranol
- Idiosyncraticdrugs are NOT dose dependant --each person needs different amt
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Term
| Done Dependent, Intrinsic Drugs |
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Definition
Acetominaphin
anti-neoplastic
mushrooms
carbon tetrachloride
ETOH |
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Term
| Acute Hepatitis takes the form of: |
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Definition
Ballooning Degeneration,
cytoplasm looks empty and containts only wisps of remnants |
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Term
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Definition
acute or chronic HEP B infetion
finely granular, eosinophilic cytoplasm shown by electron microscopy to contain massive quantities of HBSAG |
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Term
| ____ = connecting of regions of adjacent lobules, signifying a more severe form of acute heoatits |
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Definition
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Term
| in autoimmune hepatitis, what type of AB's are found? |
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Definition
Antinuclear
Anti-smooth musc
anti-soluble liver/panc ag
liker kidney microsomal ab
detectable with immunofluorescence or enzyme linked ab |
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Term
pathologic inclusions found in the cytoplasm of liver cells, often in Alcoholics
Scattered hepatocytes accumulate tangled skeins of intermediate filaments and other proteins, seen in:
Wilsons dz
primaryt biliary cirrhosis,
chronic cholestatis syndromes
hepatocellular tumores |
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Definition
Mallory bodies
They are highly eosinophilic and thus appear pink on H&E stain. The bodies themselves are made up of intermediate keratin filament proteins that have been ubiquinated, or bound by other proteins such as heat shock proteins, |
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Term
What is the main cytokine effector of liver inkury due to hep/alch
What are the main stimuli for cytokine production:
IL6
IL8
IL18 |
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Definition
TNF
-----
ROS generated during the oxidation of ETOH and PMNS
and
Endotoxins (LPS) from gut bacteria
This occurs in the centrolobular region of parenchyme |
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Term
nonalchoholic liver dz
NAFLD
and
NONALCHOHOLIC STEATOHEPATITIS
(NASH)
\Are most associated with _____ |
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Definition
insulin resistance
Obesity and type 2 diabetes are good predictors of severe fibrosis and dz progression
Insulin resistance results in the accumulation of Triglyceride in hepatocytes by three mech:
1 impaired ox of FA
2 inc synth and uptake of FA
3 dec secretion of LDLs |
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Term
| Besides overdose, a large risk exists for drug induced liver dz with patients who take ______ with _____ |
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Definition
Acetominaphine
with
Opiate
Anti-TB drug, halothane, antidepressant monoamine oxidase inhibitors also will do, carbon tetrachloride, mushrooms |
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Term
In Acetominaphine toxicity, mushrooms, carbon tetrachloride, etc
mech. of liver inj include: |
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Definition
Hepatocellular necrosis, c
cholestasis,
steatosis
steato-hepatitis,
fibrosis
vasc lesions |
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Term
| _____ = most common cause of incidental elevation of serum transaminase |
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Definition
| NAFLD -- Nonalch fatty liver dz |
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Term
| The most common form of hemochromatosis (a genetic disorder characterized by the accumulation of Fe) is |
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Definition
| an autosomal recessive dz acquired by mutation in HFE GENE |
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Term
hereditary hemochromatosis
gene resp? codes for? controlled by?
Mutations?
triad and presentation |
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Definition
Dysregulation of Fe in body
TOO MUCH ABSORPTION!
--Normally, Fe out = Fe absorbed because no excretory pathway for excess Fe
In HH, there is a defect in the regulation of intestinal absorption of Fe, --> net Fe accumulation of .5-1 gm/year
GENE Located on Chrom 6 -- Called (HFE)
Encodes protein controled by HEPCIDIN, which normally DOWN REGULATES the Absorption of Fe
Mutations to HFE = tyrosine substitute for cysteine at aa 282
or
Aspartate for histamine at aa 63
Manifests after 20 gm of storage Fe has been accumulates
3 RESULTS:
1-lipid peroxidation by fe induces ROS
2-stim of COLLAGEN Formation
3-Fe interacts with DNA
all reversable except DNA
Manifests in 5-6th decade of life
Results in hepatomegally
abd pain
skin pig
diabetes from destruct of panc cells
TRIAD:
1-cirrhosis with hepatomegally
2-skin pig
3-diabetes
treat with phlebotomy |
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Term
|
Definition
PROB WITH EXCRETION OF COPPER
accumulation of toxic levels of COPPER -- mainly liver, brain, eye
Gene on Chrom 13 -- called ATP7B encodes ATPase metal ion transporter that localized to the Golgi of hepatocytes
Copper is used in Alpha-Globulin to form ceruloplasmin
Normally excreted in BILE
Wilsons = decrease in serum ceruloplasmin, increase in hepatic copper INCREASE IN URINARY EXCRETION OF COPPER |
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Term
| Alpha-Antitrypsin deficiency |
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Definition
| Autosomal recessive disorder marked by abn low serum levels of protease inhibitors AAT is an inhibitor of proteases if it is missing, --> pulmonary emphysema because of lack of protein permits unrestrained activity of tissue-destructive proteases ***Hepatocytes in AAT def. contain round GLOBULAR INCLUSIONS of retained AAT, which stain RED in acid-schiff stain treatment - liver transplant |
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Term
| name a competitive antagoinist for epinephrine |
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Definition
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Term
What is defective in neonatal jaundice? Values?
total bilirubin indirect direct urobilinogen |
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Definition
Decreasaed UDP-Gluconyl transferase due to liver immaturity LAB: INCREASE in total bilirubin Indirect INCREASE Direct - Mild DECREASE Urine Urobilinogen - DECREASE |
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Term
Presentation: Marked Increase in total bilirubin (15-20) All INDIRECT No DIRECT no urobilinogen |
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Definition
Crigler-Najjar syndrome FATAL if type 1 |
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Term
Presentation: healthy Total bilirubin increased (less than 3) mainly indirect little direct decreased urobilinogen |
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Definition
Gilbert Syndrome HEALTHY reduced udp glucuronyl tfase |
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Term
Presentation: Total Bilirubin (2-5) indirect (less than 50% direct (greater than 50%) urobilinogen 0 Pigmaneted liver limited symptoms |
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Definition
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Term
Presentation: Asymptomatic Total Bilirubin (2-5) unconjugated (less than 50) conjugated (greater than 50) urobilinogen (0) No pigmented liver |
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Definition
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