the liver is divided into __ lobes
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?
____ is the orange-yellow pigment derived from the Hb of old RBCs
___ acids are important in cholesterol metabolism and absorption
the liver has a major role in the metabolism of ____
CHO, protein, lipid
the liver produces proteins, including ____ (4 things)
- alpha globulins
- beta globulins
- coagulation factors
the liver produces lipids, such as ____
the liver has a vital role in the catabolism of ____ and the associated synthesis of ____
Old RBCs are phagocytized throughout the __ system (bone marrow, spleen, liver Kupffer cells)
RBCs are broken down into ____ (3 things)
iron, globin and biliverdin
RBCs are broken down into iron, globin and biliverdin which is converted to ___
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
bilirubin is not soluble in water, and is loosely bound to ___ in the bloodstream and travels to the liver.
At the liver, the bilirubin is conjugated through the action of an enzyme named " ____."
TRUE OR FALSE
The conjugated bilirubin is water soluble
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
From the gallbladder, the bilirubin travels to the small intestine. There it is converted into ____ through the action of bacteria
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.
Some urobilinogen is reabsorbed into the circulation and excreted in urine. Thus, there is ___ some urobilinogen in "normal" urine.
As far as blood testing is concerned, conjugated (or Direct) and Unconjugated (or Indirect) bilirubin make up ___
- ___ soluble
- ___ in urine
- ___ morbidity
- ___ jaundiced appearance
- water soluble
- present in urine
- lower morbidity
- more jaundice appearance
- ___ 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)
this type of jaundice is due to hemolysis (hemolytic anemia - HA, and hemolytic disesae of the newborn- HDN Increased IBili
this type of jaundice is due to a due to hemolysis (hemolytic anemia - HA, and hemolytic disesae of the newborn- HDN Increased IBili
this type of jaundice is outside of liver, blocking of bile duct by stone, tumor etc. DBili very high.
In Pre-Hepatic jaundice (e.g., Hemolytic Disease of the Newborn - HDN, Hemolytic Anemia - HA), the ____ bilirubin is the predominent fraction.
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
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.
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.
____ is the substance that gives stools their characteristic brown color, and in obstructive jaundice the stools become ____ colored.
The patients have the greatest "yellow appreance" with ___ jaundice.
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.
___ is jaundice affecting the brain and CNS that results from bilirun levels >18-20 mg/dL
Pathological kernicterus can lead to ___ and ___
mental retardation and death
The infants with bilirubins > 8mg/dL may be treated with ___.
Bilirubin is ___senstive, and is either destroyed or made non-toxic by the light.
A transfusion may be necessary if the Bili is > __ mg/dl
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?
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?
Typically Total and __ bilirubin are measured, and ____ bili is calculated.
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
what 9 viruses can cause viral hepatitis?
- herpes viruses
how is HAV transmitted?
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?
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?
how long after exposure does HCV sometimes appear?
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 ____
the reference range for AST and ALT is generally ___
<40 or 45 IU/L
an increase of ___-___x the reference range, disease is indicated
AST and ALT will rise with ___, but are more specific to liver than other enzymes
what is the other name for AST?
Serum Glutamyl Oxaloacetate Transaminase (SGOT; OT)
where are the largest concentrations of AST?
where else (other than heart and liver) is AST found?
- skeletal muscle
what is the other name for ALT?
Serum Glutamyl Pyruvate Transaminases (SGPT; PT)
where is ALT primarily found?
what is the diagnostic significance of increased ALT?
what type of hepatitis does ALT rise significantly with?
what other liver diseases increase ALT (6)?
- 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 : 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)?
what is the diagnostic significance of ALP?
evaluation of HEPATOBILIARY and BONE disorders
ALP increases dramatically with ____ jaundice
what is another name for obstructive jaundice?
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?
growing children have a __-__x higher ALP
what happens to ALP in complications of pregnancy (e.g. preeclampsia)?
when might you get a falsely elevated ALP?
- serum not separated from cells
- serum not iced before analysis
where is GGT found? (5 places)
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?
what 3 other conditions (besides obstructive jaundice and occult alcoholism) can increase GGT?
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 ___
when is 5'N increased?
liver disease (almost ALL)
what type of jaundice graetly increases 5'N?
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)?
what is the reference range for lipase (LIP)?
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?
- acute cholecystitis
- intestinal obstruction
what are 2 conditions in which AMS might increase alone?
amylase should be cleared within __-__ days after peaking
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?
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
the gamma globulins are synthesized by ___
what are the 7 functions of proteins?
- general body protein needs
- 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 ___
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?
- long standing GI diseases
what can cause insufficient protein synthesis?
chronic liver disease
what 3 things can cause excessive protein breakdown?
- hypermetabolism (uncontrolled DM)
- acute insults (fever, trauma)
what 3 things can acuse a loss of protein?
- renal disease
- 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
in an ALKALINE buffer, proteins become ____ charged; but in different proportions as determined by their molecular structure and isolelectric point (PI)
if a protein is not at its isoelectric point, it will become charged and ___ in an electric field
the separation of proteins can be scanned by e a____ resulting in a series of peaks in proportion to the amount present
the peaks in PEL scans represent groups of proteins, namely ___
- albumin (tallest)
- alpha 1
- alpha 2
table of characteristics of protein groups
albumin + ____ = total proteins
how are albumin and total protein typically done?
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
___ is the first assessment of whether or not protein proportion are in the healthy range
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
- 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
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 ___
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
what 3 conditions in pregnancy can be determined via AFP?
- open spina bifida
- intrauterine death
AFP can be used for detection of spina bifida at __ weeks
what are the 2 alpha 2 globulins?
in intravascular hemolysis, haptoglobin combines with hemoglobin to prevent ____
hemoglobin-haptoglobin complex is too large to pass through the ___
ceruloplasmin contains more than 90% of plasma ___-____ carrying protein
ceruloplasmin is decreased with ____ disease (resulting in COPPER DEPOSITS throughout the body)
ceruloplasmin is increased with ___ syndrome
what are the 3 beta globulins?
- C3 complement
what is the function of transferrin?
transport of iron
normally, transferin is ___ saturated with iron
usually, transferin is measured as ___
transferin is increased with ___, decreased with other ___
C3 complement functions in the ___ of foreign cells
CRP is a sensitive but non-specific ___
CRP activates ___
CRP is a high sensitivity CRP used as a ___ marker
what are the 5 types of gammaglobulins?
kappa and lambda are ___ chains
IgG and all the other antibodies are increased in ____
mutliple myeloma (Bence Jones proteins)
IgM is increased in ___
all antibodies are increased in __
all antibodies are decreased in ___ and ____
prealbumin migrates ___ than albumin, but albumin overlaps it in PEL so typically you _____
faster; do not see it
what is the function of prealbumin?
transport 2 plasma proteins at 2 different binding sites
what are the 2 types of prealbumin?
- thyroxine binding prealbumin (TBPA)
- vitamin transporting protein
what is the function of thyroxine binding prealbumin?
Vitamin A Transporting Protein binds to ____
retinol/vitamin A binding protein (RBP)
Binds to retinol/(Vit. A) binding protein (RBP) to form prealbumin-RBP-Vitamin A complex: transports complex is released to unload ___ onto cell membrane
vitamin a transporting protein is used in a ___ work up
fibrinogen and plasminogen is a coagulation factor; it migrates between beta and gamma region. it is a 6th normal PEL band if present, but only seen if the specimen used is ___
___ are abnormal globulins that precipitate in cool serum and redissolve upon warming or returning to room temperature
Cryoglobulins appear with a variety of diseases such as ___ (5 things)
- multiple myeloma
- rheumatoid arthritis
- other autoimmune diseases
Cryoglobulins may gel out in the blood when circulating in the cooler extremities. Thus, clinically, cryoglobulins resemble ____ -- patients are intolerant to cold and are susceptible to gangrene of the extremities and skin sores. Death can result from blockage of key blood vessels
For ___, the specimen should be allowed to clot at 37 C so the protein stays in the serum. Then the serum is cooled from 48-72 hours at 10 C and observed for gel formation
Acute phase reactants (APR) are proteins whose concentrations increase in association with ___ (4 things)
- inflammatory stimulus
APRs are mostly found in ___ and ___ fractions
alpha and beta
APRs are all synthesized in the ___
what 7 things increase in response to inflammatory stimulus?
- Orosomucoid (Acid glycoprotein)
- C3 complement component
- C-reactive protein
picture of changes in proteins in variable conditions
PEL PATTERN = ______
Usual PEL pattern of albumin, alpha 1, alpha 2, beta and gamma. Albumin migrates the fastest because it has the lowest PI and thus picks up most negative charge in an alkaline buffer because its buffering capacity is saturated and it becomes the most anionic (negatively charged) protein and moves fastest to the Anode or positive pole. The remaining proteins, which are globulins, follow suit in proportion to their PIs.
PEL PATTERN = ______
One immunoglobulin is being produced and the other ones are turned off thus producing a monoclonal peak in the gamma region. Pattern is seen with multiple myeloma and Waldenstroms Macroglobulinemia where the gammaglobulin is IGM. Sometimes in MM, the monoclonal peak can move into the beta region so only four peaks are visible.
PEL PATTERN = ______
conditions like this, e.g. VD, TB, aids produces this "haystack" effect in the gamma region. This is because all the immunoglobulins are increased (e.g. IGG, IGM, IGA, IGE etc.) This is in contrast to Acute infections where the alpha and beta globulins are increased.
PEL PATTERN = ______
this condition is a tell-tale sign of cirrhosis of the liver usually due to alcoholism. The liver may lose its functionality and turn "fatty." Also, the urea cycle may break down resulting in increased ammonia in circulation leading to hepatic coma and death.
PEL PATTERN = ______
The smallest MW proteins are lost first. That means albumin, then the immunoglobulins. The highest MW proteins are in the alpha 2 band, so this shows a "peak" by default
IEL/IF combine electrophoretic separation of proteins with __-___ reactions with the separated protein groups
in immunoelectrophoresis and immunofixation, a pattern of anti-__ precipitate streaks or arcs is produced, each one corresponding to a specific protein
IEL is considered a "____" technique
The ___ patterns of the patient are compared to those of a control and are "judged" as being in increased, decreased or "normal" compared to the control pattern
IEL shows an increase in the IGG monoclonal antibody, IGA and IGM immunoglobulins are decreasedcompared to the reference control. This pattern is indicative of an IGG _____
IEL shows an increase in the IGA monoclonal antibody, IGG and IGM immunoglobulins are decreased compared to the reference control. This pattern is indicative of an IGA ____
IEL shows an increase in the IGM monoclonal antibody, IGG and IGA immunoglobulins are decreased compared to the reference control. This pattern is indicative of ____ or _____
IGM monoclonalgammopathy or Waldenstrom's macroglobulinemia
IEL shows an increase in the lambda type immunoglobulin light chains. Heavy chain antibodies appear similar or decreased relative to the reference control, indicative of ___
light chain (gamma) Bence Jones monoclonal gammopathy