(3) Liver Function

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the liver is divided into __ lobes

2

the liver is fed by 2 circulatory systems; one from the ____ (___) and one from the ____

intestine (portal vein), hepatic artery

what are the 4 functions of the liver?

- detox
- excretion
- synthesis
- metabolic

____ is the orange-yellow pigment derived from the Hb of old RBCs

bilirubin

___ acids are important in cholesterol metabolism and absorption

bile acids

the liver has a major role in the metabolism of ____

CHO, protein, lipid

the liver produces proteins, including ____ (4 things)

- albumin
- alpha globulins
- beta globulins
- coagulation factors

the liver produces lipids, such as ____

- TGs
- cholesterol
- phospholipids

the liver has a vital role in the catabolism of ____ and the associated synthesis of ____

ammonia, urea

Old RBCs are phagocytized throughout the __ system (bone marrow, spleen, liver Kupffer cells)

RE

RBCs are broken down into ____ (3 things)

iron, globin and biliverdin

RBCs are broken down into iron, globin and biliverdin which is converted to ___

bilirubin

RBCs are broken down into iron, globin and biliverdin which is converted to bilirubin This form of bilirubin is called ____ (aka ____)

"unconjugated bilirubin," also known as "indirect bilirubin.

TRUE OR FALSE
indirect bilirubin is soluble in water

false

bilirubin is not soluble in water, and is loosely bound to ___ in the bloodstream and travels to the liver.

albumin

At the liver, the bilirubin is conjugated through the action of an enzyme named " ____."

glucuronyl transferase

TRUE OR FALSE
The conjugated bilirubin is water soluble

true

Conjugated bilirubin is collected in the liver in the ____ vessels which drain into increasingly larger vessels that lead to the hepatic duct and the common bile duct with the gallbladder where it is stored

canaliculi

From the gallbladder, the bilirubin travels to the small intestine. There it is converted into ____ through the action of bacteria

urobilinogen

From the gallbladder, the bilirubin travels to the small intestine. There it is converted into urobilinogen through the action of bacteria, which then converts to ____ in the large intestine and excreted in stool.

urobilin

Some urobilinogen is reabsorbed into the circulation and excreted in urine. Thus, there is ___ some urobilinogen in "normal" urine.

always

As far as blood testing is concerned, conjugated (or Direct) and Unconjugated (or Indirect) bilirubin make up ___

Total bilirubin

DIRECT RILIRUBIN
- ___ soluble
- ___ in urine
- ___ morbidity
- ___ jaundiced appearance

- water soluble
- present in urine
- lower morbidity
- more jaundice appearance

INDIRECT RILIRUBIN
- ___ soluble
- ___ in urine
- ___ morbidity
- ___ jaundiced appearance

- not water-soluble (nonpolar)
- not in urine
- high morbidity
- lesser jaundice appearance

If Total Bilirubin increases to __-__, the pateint will exhibit jaundice

2.5 - 3.0

In jaundice, ___ also dark yellow to brown or green (as bilirubin levels increase)

serum

this type of jaundice is due to hemolysis (hemolytic anemia - HA, and hemolytic disesae of the newborn- HDN Increased IBili

pre-hepatic

this type of jaundice is due to a due to hemolysis (hemolytic anemia - HA, and hemolytic disesae of the newborn- HDN Increased IBili

hepatic

this type of jaundice is outside of liver, blocking of bile duct by stone, tumor etc. DBili very high.

post-hepatic

In Pre-Hepatic jaundice (e.g., Hemolytic Disease of the Newborn - HDN, Hemolytic Anemia - HA), the ____ bilirubin is the predominent fraction.

indirect

In Pre-Hepatic jaundice (e.g., Hemolytic Disease of the Newborn - HDN, Hemolytic Anemia - HA), the indirect bilirubin is the predominent fraction. This is because ____.

the amount of RBC destruction is significant before the bilirubin gets to the liver

In Hemolytic Jaundice, the bilirubin is not as elevated as in the other forms of jaundice. Here, the IB is ____ the DB because the liver is overwhlmed and cannot conjugate the bilirubin being produced efficiently and fast enough

greater than

Only in Post-Hepatic jaundice (e.g., obstruction of the biliary track by a stone or growth), does the ____ bilirubin rise to a notable level, often becoming the major bili fraction.

direct

Only in Post-Hepatic jaundice (e.g., obstruction of the biliary track by a stone or growth), does the direct bilirubin rise to a notable level, often becoming the major bili fraction. In these cases, urobilinogen is not produced and, therefore, is ____ in the urine, nor is urobilin produced.

negative

____ is the substance that gives stools their characteristic brown color, and in obstructive jaundice the stools become ____ colored.

Urobilin, white-clay

The patients have the greatest "yellow appreance" with ___ jaundice.

obstructive

Newborns may exhibit jaundice. Most often this is due to the ____

immaturity of the liver.

the reference range for bilirubin is ___ for infants than for adults.

higher

___ is jaundice affecting the brain and CNS that results from bilirun levels >18-20 mg/dL

kernicterus

Pathological kernicterus can lead to ___ and ___

mental retardation and death

The infants with bilirubins > 8mg/dL may be treated with ___.

UV light

Bilirubin is ___senstive, and is either destroyed or made non-toxic by the light.

photo

A transfusion may be necessary if the Bili is > __ mg/dl

20

what is the total bilirubin reference range?

05. - 1.2 mg/dL

what is the direct bilirubin reference range?

0.0 - 0.2 mg/dL

what is the newborn bilirubin reference range?

<10 mg/dL

Bilirubin is performed on SERUM or PLASMA and should be drawn in a ___, ___, or ___ tube.

SST, red top, or heparin

does the patient have to be fasting for bilirubin?

no

Typically Total and __ bilirubin are measured, and ____ bili is calculated.

Direct, indirect

this type of hepatitis is chronic, progressive, and irreversible

alcoholic or acute alcoholic hepatitis

this type of hepatitis is the most common cause of liver cell damage

viral hepatitis

what 9 viruses can cause viral hepatitis?

- HAV
- HBV
- HCV
- HDV
- HEV
- CMV
- coxsackievirus
- EBV
- herpes viruses

how is HAV transmitted?

fecal-oral route

what is the antibody and liver enzyme pattern in HAV?

- IgM antibodies in ACUTE phase
- AST and ALT elevated
- virus in feces
- acute phase can last more than a year

- IgG antibdoies persist after acute phase FOR LIFE

what is the prognosis for HAV?

vast majority recover with few sequelae

how is HBV (serum hepatitis) transmitted?

parenterally

what is the pattern of antigens and antibodies in HBV infection?

- first marker is HBsAg (HBV surface antigen)
- then enzymes elevated
- anti-HBs along with anti-HBc
- IgM in first 6 months
- IgG after 6 months

what 2 conditions are HBV associated with?

- chronic hepatitis
- liver cancer

how is HCV transmitted?

parenterally

how long after exposure does HCV sometimes appear?

20-30 years

what is difficult about HCV?

- many genotypes (at least 6)
- mutates frequently; hard for body to get rid of
- infection does not confer immunity

AST and ALT are aka ____

transaminases

the reference range for AST and ALT is generally ___

<40 or 45 IU/L

an increase of ___-___x the reference range, disease is indicated

200-300

AST and ALT will rise with ___, but are more specific to liver than other enzymes

MI

what is the other name for AST?

Serum Glutamyl Oxaloacetate Transaminase (SGOT; OT)

where are the largest concentrations of AST?

- liver
- heart

where else (other than heart and liver) is AST found?

- kidneys
- skeletal muscle
- pancreas
- lungs
- brain
- RBC
- WBC

what is the other name for ALT?

Serum Glutamyl Pyruvate Transaminases (SGPT; PT)

where is ALT primarily found?

ALT

what is the diagnostic significance of increased ALT?

hepatic disorders

what type of hepatitis does ALT rise significantly with?

viral

what other liver diseases increase ALT (6)?

- cirrhosis
- Reyes
- hepatomas
- chronic hepatocellular IM
- alcohol intake
- liver CA

the AST/ALT ratio can differentiate between ____

- acute or chronic
- intra- or extrahepatic syndrome

what is the reference ratio for AST/ALT?

1.15

(1 : 0.87)

what is the general rule of thumb for AST and ALT?

ALT > AST = hepatitis
ALT < AST = cirrhosis

table of AST/ALT ratios

what are the tissue sources of ALP (6)?

- intestine
- liver
- bone
- spleen
- kidney
- placenta

what is the diagnostic significance of ALP?

evaluation of HEPATOBILIARY and BONE disorders

ALP increases dramatically with ____ jaundice

obstructive

what is another name for obstructive jaundice?

cholestasis

ALP increases with ____ disease (____) in bones

Paget's disease (osteitis deformans)

what 3 other conditions (besides obstructive jaundice and Paget's) cause an increased ALP?

- osteomalacia (Ricketts)
- healing fractures
- bone CA

what happens to ALP in pregnancy and growing children?

increases

growing children have a __-__x higher ALP

2-3x

what happens to ALP in complications of pregnancy (e.g. preeclampsia)?

great increase

when might you get a falsely elevated ALP?

- serum not separated from cells
- serum not iced before analysis

where is GGT found? (5 places)

- liver
- kidney
- brain
- prostate
- pancreas

when does GGT greatly increase?

obstructive jaundice (cholestasis)

why is GGT useful for confirming ALP elevation due to liver disease?

because GGT is normal in bone diseases

what can GGT be an indicator of?

occult alcoholism

what 3 other conditions (besides obstructive jaundice and occult alcoholism) can increase GGT?

- DM
- pancreatitis
- MI

what is the reference range for GGT in females and males?

females < 40 IU/L
males < 40 IU/L

5' Nucleotidase (5'N) is a ___

phosphatidase

when is 5'N increased?

liver disease (almost ALL)

what type of jaundice graetly increases 5'N?

obstructive

why is 5'N useful to confirm elevated ALP due to liver disease?

because 5'N is normal or only slightly elevated in bone disease

when are pancreatic enzymes typically measured?

suspected cases of pancreatitis

what does amylase do?

hydrolyze breakdown of starch and glycogen

what does lipase do?

hydrolyze ester linkages of fats to produce alcohols and fatty acids

what are the tissue sources of amlyase and lipase?

pancreas and salivary glands

what is the reference range for amylase (AMS)?

50-150

what is the reference range for lipase (LIP)?

<1.0 IU/L

is AMS or LIP typically on the STAT list?

AMS (LIP used more for confirmation and monitoring)

what are 3 conditions that might increase pancreatic enzymes?

- ulcers
- acute cholecystitis
- intestinal obstruction

what are 2 conditions in which AMS might increase alone?

- mumps
- parotiditis

amylase should be cleared within __-__ days after peaking

3-5

how can you get a better understanding of whether or not the kidney is confounding the interpretation of the course of the disease? (3 things)

- measuring amylase in urine
- measuring amylase in serum
- comparing clearing of amylase to that of creatinine

what is the healthy population reference range for the amylase creatinine ratio?

< 3%

what is a distinguishing feature of proteins?

the presence of nitrogen (makes up about 16% of all proteins)

with the exception of gamma globulins and some enzymes, the ____ virtually exclusively synthesizes the plasma proteins

liver

the gamma globulins are synthesized by ___

plasma cells

what are the 7 functions of proteins?

- general body protein needs
- defense
- repair
- coagulation
- body pH
- osmotic balance
- regulation of cellular activity and function (enzymes, hormones, transport)

often, the decrease in total protein is due to a decrease in ___

albumin

what are 4 reasons for decreased protein concentration?

- insufficient intake of protein
- insufficient protein synthesis
- excessive protein breakdown
- loss of protein

what 3 things can cause an insufficient intake of protein?

- starvation
- malnutrition
- long standing GI diseases

what can cause insufficient protein synthesis?

chronic liver disease

what 3 things can cause excessive protein breakdown?

- hypermetabolism (uncontrolled DM)
- hyperthyroidism
- acute insults (fever, trauma)

what 3 things can acuse a loss of protein?

- renal disease
- hemorrhage
- extensive skin lesions (burns, exfoliative dermatitis)

what 3 things can increase concentration of protein?

- minor elevations due to hemoconcentration in ACUTE DEHYDRATION

- multiple myeloma and Waldenstrom's macroglobulinemia due to increased levels of globulins

- minor elevations due to increased gamma globulin in infection (rare)

what is one of the most descriptive and available in house ways to separate proteins?

Protein Electrophoresis (PEL)

what is separation of proteins based on ?

the molecular structure of the various proteins (i.e. carboxyl group and amino groups)

____ can be described as movements of charged particles in en electric field

electrophoresis

in an ALKALINE buffer, proteins become ____ charged; but in different proportions as determined by their molecular structure and isolelectric point (PI)

negatively

if a protein is not at its isoelectric point, it will become charged and ___ in an electric field

migrate

the separation of proteins can be scanned by e a____ resulting in a series of peaks in proportion to the amount present

densitometer

the peaks in PEL scans represent groups of proteins, namely ___

- albumin (tallest)
- alpha 1
- alpha 2
- beta
- gamma

table of characteristics of protein groups

albumin + ____ = total proteins

globulins

how are albumin and total protein typically done?

automated analyzers

normally, albumin is __% of the total protein (therefore the globulins must be _% with a resulting A/G ratio of __)

- albumin 50%
- globulins 50%
- A/G ratio of 1

the A/G will be __ if the
- globulins rise
- albumin decreases

<1

___ is the first assessment of whether or not protein proportion are in the healthy range

A/G

the A/G is a ___ (not ___) indicator of disease

general (not specific)

total protein, albumin, calculated globulins, and A/G ratio are relatively readily available and part of a comprehensive metabolic panel usually available 24/7. ___, ___, and ____ are special chemistry tests that are not automated and may be offered 1x a day or every other day

- electrophoresis
- immunoelectrophoresis
- individual protein quantification

what are the 5 functions of albumin?

- nutrition for tissues
- osmotic equilibrium and water distribution
- pH buffering
- mineral binding (Ca and Mg)
- transport of hormones, bilirubin, FAs, drugs

the causes of decreased albumin are similar to ___

that of total protein

what causes increased albumin?

acute dehydration where hemo-concentration results

what are the 2 types of alpha1 globulins?

- alpha 1 antitrypsin (alpha1AT)
- alpha 1 fetoprotein (AFP)

alpha1 antitrypsin is the
- ___ plasma protein of the alpha 1 globulins
- synthesized in the ___
- responsible for nearly all ___ activity of serum

- main
- liver
- protease

what does an alpha 1 antitrypsin deficiency cause?

- early COPD
- neonatal hepatitis
- hepatic cirrhosis

alpha 1 antitrypsin is an ___

acute phase reactant

alpha1 fetoprotein (AFP) is found in the ____

12 week fetus (up to 5 weeks after birth)

when does AFP peak?

at 12-15 weeks of gestation amniotic fluid

AFP is seen in maternal blood up to the ___

8th month

AFP is found in adults with _____ and in 1/3 of patients with ____

= primary CA of the liver
- tetatoma (tumor cells which revert to fetal functions)

because of AFPs increase in liver cancer and tetatoma, it is a useful ___ aid

diagnostic

what 3 conditions in pregnancy can be determined via AFP?

- open spina bifida
- anencephaly
- intrauterine death

AFP can be used for detection of spina bifida at __ weeks

18

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