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Clinical Chem: Liver & GI Function/Disease Flashcards

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1
Q

The organs that make up the G.I. Tract are:

A

The Liver, Gallbladder, Pancreas, Stomach, Duodenum, Small Intestine (Jejunem & Ileum), and the Colon.

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2
Q

Where is the liver located?

A

In the right, lower quadrant underneath the diaphragm.

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3
Q

Describe the blood flow of the following: the Hepatic Artery, Hepatic Vein, and Portal Vein.

A

Fresh oxygenated blood flows into the liver from the aorta through the hepatic artery and de-oxygenated blood leaves returning to the heart through the hepatic vein. The portal vein contains blood and other products absorbed in/from the GI tract flowing into liver.

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4
Q

The functions of hepatocytes, bile duct and Kupffer cells are:

A

Hepatocytes- Metabolic functions of the liver
Bile Duct- Excretory products to gallbladder
Kupffer cells- Stationary macrophages which filter portal blood of bacteria , toxins, etc.

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5
Q

What are the general functions of the liver?

A
  1. Excretory and Secretory functions
  2. Synthesis
  3. Detoxification
  4. Storage (iron, glycogen)
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6
Q

Heme/Bilirubin Metabolism is an example of what general function of the liver?

A

Excretory/Secretory

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7
Q

Where are the red blood cells broken down ?

A

The reticulendothelial (RE) system

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8
Q

Imagine a mass of red blood cells have been broken down. Visualize and describe the next steps to completion of Heme/Bilirubin Metabolism in the liver.

A

1) After the breakdown of RBCs, iron is taken by transferrin to the bone marrow or storage, and globin proteins are recycled to amino acids.
2) Heme is then oxidized to BILIVERDIN
3) BILIVERDIN is reduced to BILIRUBIN
4) Albumin binds BILIRUBIN and goes to the liver/hepatocytes.
5) BILIRUBIN conjugated to GLUCURONIDE
6) BILI-GLUCURONIDE excreted into bile canaliculis to Gall Bladder and Duodenum

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9
Q

Heme/Bilirubin metabolism in 3 steps

A

1) Bilirubin transported to hepatocytes
2) Glucuronidation of bilirubin
3) Bili-glucu then excreted into canaliculus

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10
Q

Short answer:

________ metabolizes conjugated bilirubin to __________ in the gut.

A

Intestinal flora.

Urobilinogen (colorless)

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11
Q

Stool has a brown (ish) color because…..

A

In the gut urobilinogen oxidizes to urobilin (80%). Urobilin gives stool its color.

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12
Q

Only 80% of urobilinogin is oxidized in the gut. What happens to the remaining 20%?

A

Remaining urobilinogen can be reabsorbed (entero-hepatic circulation) and re-excreted or filtered by the kidney.

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13
Q

An increase of urinary urobilinogen is indicative of __________________.

A

Increased bilirubin excretion into bile.

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14
Q

Pale/colorless stool is an important clinical sign. It is indicative of what?

A

The lack of bilirubin in the gut.

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15
Q

Bile acids, aka bile salts, are formed by the metabolism of __________. Then excreted into ________, and stored in the ________.

A

Cholesterol
Bile
Gallbladder

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16
Q

What function do bile salts perform?

A

Bile salts emulsify dietary fats for lipase hydrolysis.

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17
Q

Though testing is possible for bile salts, is it significant/valuable?

A

Bile salts are increased with liver disease but add no additional value to other tests.

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18
Q

What is synthesized in the liver?

A 
1 Albumin
2 Clotting Factors
3 Most proteins (except Hb and immunoglobulins)
4 Carbs(glucose, glycogen)
5 Lipids (cholesterol and triglycerides)
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19
Q

Half-life of Albumin?

A

2-3 weeks (has a slow response to decreased synthesis)

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20
Q

Function of albumin?

A

1) Transport of drugs, and ions (Ca2+)

2) Helps maintain plasma water volume via oncotic.

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21
Q

Where are all clotting factors synthesized?

How many are Vitamin K dependent?

A

The liver.

Several.

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22
Q

Prothrombin time (PT) and Partial thromboplastin time (PTT) are ________assays and can be prolonged by ____________________.

A

Clotting assays.

Decreased synthesis of clotting factors

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23
Q

What does “first pass” refer to?

A

Contents of the GI system go to the liver first via the portal vein before hitting general circulation. the liver may metabolize toxins to less toxic molecules. (example: cytochrome P450 system)

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24
Q

Is Ammonia dangerous to the human body?

A

YES! It is very toxic especially to the CNS.

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25
Ammonia is a product of protein metabolism. How is the toxic accumulation of Ammonia prevented?
The liver gets "first pass" of gut bacterial ammonia. | Also Urea cycle in the liver prevents NH3 accumulation.
26
Liver Function Tests (LFTs) are a standard test group in most labs, however not every test in the panel DEFINES liver function. List the seven tests that make up the "Hepatic function panel" as defined by the AMA.
``` 1 Total Protein 2 Albumin 3 AST 4 ALT 5 ALP 6 Total Bilirubin 7 Direct Bilirubin ```
27
What is ALT shorthand for? AST? ALP?
Alanine Aminotransferase Alkaline Phosphatase Aspartate Aminotransferase
28
What type of reaction is used to test total protein?
A biuret reaction in alkaline medium where cupric copper reacts with peptide backbones independent of amino acid side chains. The biuret test is a chemical test used for detecting the presence of peptide bonds. In the presence of peptides, a copper(II) ion forms violet-colored coordination complexes in an alkaline solution. (wikipedia)
29
What is the reference interval of Total Protein?
6.0-8.0 gm/dL
30
Total protein is increased when?
Dehydration, increased synthesis (mult. myeloma), & extended tourniquet time
31
Total protein is decreased when?
Decreased synthesis( liver disease, severe malnutrition) Increased loss ( kidney, GI tract, burns)
32
__________ and ___________ bind to albumin causing a ______in the absorbance peak.
``` Bromcresol green (BCG), Bromcresol purple (BCP), shift ```
33
What is the affect of hemolysis on BCG? | What is the affect of bilirubemia and renal disease on BCP?
Hemolysis causes BCG to be overestimated. | Renal Disease and Bilirubinemia causes BCP to be underestimated.
34
What is the reference interval for Albumin?
3.5-5.0 gm/dL
35
When may the albumin be increased? | Decreased?
Dehydration and increased tourniquet time can cause an increase in albumin levels. Decreased synthesis (liver disease), Increased loss (GI, burns, renal) and nutritional deficit (late) can cause a decrease in albumin levels. (The same as in total protein)
36
What is transaminitis?
What MDs call elevations in ALT and AST
37
Where are the Aminotransferases found?
Within hepatocytes
38
AST and ALT are involved in ______metabolism which are Vitamin ______dependent reaction and may be added to __________.
Amino Acid B6 Reagent
39
ALT and AST are not liver function specific but are a marker for hepatocellular integrity, why?
Because they are released during hepatocyte necrosis (cell death)
40
Which is somewhat liver specific? ALT or AST?
ALT. AST has poor tissue specificity.
41
What are alternate names for ALT and AST?
Glutamate-pyruvate transaminase & Aspartate-oxaloactetate transaminase.
42
The assays for ALT and AST are ___________ assays that measure ___________absorbance at 340 nm.
Kinetic. | Decreasing.
43
ALP is short for ___________
Alkaline Phosphatase.
44
ALP is associated with __________canaliculi and ___________induces the synthesis of ALP.
Biliary. | Biliary obstruction. (however ALP is NOT a marker of cellular integrity and is greater in EXTRA hepatic obstruction.
45
ALP is an (isoform/or soenzyme) and (is or isn't) tissue specific.
ALP is an isoform and isoenzyme. One unspecific form has post glycosylation variations in liver, bone and kidney ISOFORMS from ONE GENE. Also placental and intestinal isoenzymes from 2 other genes.
46
In adults the ____________ ALP dominates and in children the ___________ ALP dominates.
Liver | Bone
47
How is ALP measured?
By the hydrolysis of p-nitrophenyl phosphate at pH= 10.3
48
What sample types cannot be used by the assay for ALP? Why ?
The hydrolysis requires Mg2+ and Zn2+. | Cant use anticoagulants that chelate divalent cations. So gray, lavender and blue tops are a no go.
49
The hydrolysis of p-nitrophenyl absorbs at _______ which is around the same as hemoglobin. It is an ____ rate reaction.
405/415 nm | Increasing
50
ALT and AST are _______ dependent, whereas ALP is ___ dependent.
sex | age
51
What increases ALP by 2%?
Refrigeration
52
ALP is method dependent and higher in which populations?
In growing children and during pregnancy (placental)
53
GGT should be included in the liver panel instead of AST,why?
Ganna-glutamyltransferase is a much more specific marker for hepaobiliary disease than ALP (though may not be more sensitive) Elevated in alcoholics but poor sensitivity.
54
Plasma source of GGT is mostly liver, but where else?
kidney, pancreas and intetsine
55
Why is it important that bilirubin is tightly bound to albumin in circulation?
To prevent uptake by fatty tissue eg: brain
56
What are the three forms of bilirubin?
1 Conjugated bili 2 Unconjugated bili (poor solubility) 3 Delta bilirubin (covalently bound to albumin)
57
Delta bili is a reult of prolonged ______ elevation. Why does it take time for its concentration to go down?
Bilirubin because its bound to albumin and breaks down when albumin's half life of 2-3 wks is up instead of 24 hr. Can be confusing for some Drs. No way to measure easily
58
What method is typically used to measure bilirubin?
Jendrassik-Grof method: Diazotized sulfanilic acid derivative reacts with SOLUBLE bilirubin to form a colored product
59
What does direct bilirubin measure?
The conjugated and delta bilirubin (ref range is 0-.3) mg/dL
60
How do we measure Total Bilirubin?
By adding an accelerant of caffeine benzoate the albumin-bound uncinjugated bilirubin becomes more soluble. Total Bili measure the conj, unconj and delta forms (most people dont have) of bilirubin. Reference interval is (.2-1) mg/dL
61
How would we get the Indirect Bili calculation?
Total minus Direct
62
What does light do to bilirubin?
Degrades it | Hemolysis also affects bili assays
63
Jaundice is a clinical sign of ____________. Where will it show?
increased bilirubin | skin, whites of eyes, nail bed, etc. aka icterus
64
What is icterus?
Laboratory evidence of bilirubin in serum and plasma
65
What can cause pre hepatic jaundice?
Hemolytic processes, ineffective erythropoiesis | and internal bleeding
66
With pre hepatic jaundice the bilirubin is primarily ________. is the live capable of conjugating increased loads?
Unconjugated. | Yes, loads usually dont exceed 5 mg/dL
67
Hepatic Jaundice can be due to?
Congenital defects in metabolism | Acute liver disease
68
What are three Congenital Bilirubin disorders:
1 Gilberts syndrome (1-3 mg/dL unconj bili-benign) 2 Crigler-Najjar syndrome (conj defect so increase in indirect bili.Type I is fatal with complete absence and indirect bili >25. Type II 5-20 just partial deficiency and not fatal. 3 Dubin-Johnson and Rotor syndromes Defect in conj bili transport into bile. Increased direct bili-benign
69
Why is Neonatal jaundice normal the first few days?
High RBC turnover Prematurity Breastfeeding (mom steroids inhibit glucuronidation and milk hydrolyzes conj bil)
70
What is Kernicterus?
Deposition of bilirubin in the brain. | Bilirubin exceeds albumin inding capacity so high ind bili. This can result in death and /or perm. brain damage.
71
What is the critical value range for neonatal jaundice? | Treatment?
15-20 mg/dL | phototherapy or exchange transfusion
72
How is neonatal bili measured?
Simple spectrophotometric assays -no diazo rnx, hemolysis does not affect, 450 nm absorb. peak in diluted sample ``` Transcutaneous measurment (POC) -multiwavelength reflectance though sternal skin, correlation but not equivalent to serum, skin color issue ```
73
Bhutani diagram helps......
figure out which treatment to use in neonates for jaundice (bili vs age in hrs)
74
What can cause post hepatic jaundice?
1) Decreased excretion of bili: Increase in direct bili, pale stool ( lol urobilin in GI tract), bilirubiuria (conj bili filtered by kidney) 2) Intra hepatic (liver disease-alter excretion ability 3) Extra hepatic: physical blockage of biliary ducts gallstones/tumors)-cholestasis (obstructive/regurgitation)
75
Where does the liver get ammonia?
It scavenges ammonia from bacteria in the GI tract
76
Increased Ammonia is a neurotoxin. When would blood ammonia so elevated? What is it converted to to avoid toxicity? What can increased ammonia lead to?
sever liver failure Urea hepatic encephalopathy
77
What can increase Ammonia load? | What can i,pair Ammonia metabolism?
GI bleeding | cirrhosis and fulminant hepatitis
78
How is NH3 measured?
spec: decreasing absorbance at 340 Ammonia + alpha-KG + NADPH= Glutamate+ NADP+ enzyme is GDH
79
Why is NH3 a stat?
Ammonia is unstable. Collect in green or lav top
80
Why put ammonia on ice?
Deamidation of amino acids form ammonia
81
What is acute hepatitis? Causes?
-Inflammation of liver affecting hepatocytes. | Caused by: viral infection, toxins, and autoimmunity
82
What are the predominant lab findings in acute hep?
High ALT ans AST ALP and GGT mild because more of biliary tree indicators bili increase with prolonged disease
83
What is ischemic toxic acute hepatitis? | What lab test is affected?
Inadequate blood supply to liver AST higher but ALT longer half life probable coag test prolongation
84
What are causes of Chronic Hepatitis?
Viral (B&C), non alcoholic fatty liver disease and NASH, Hemochromatosis, Wilson's disease (copper accumulation), autoimmune hep, antitrypsin deficiency, primary biliary cirrhosis
85
Define cirrhosis. | What are the major symptoms?
Liver fibrosis due to chronic hepatitis (incl B and C) or cholestastis, or alcoholism. Diminished blood flow in liver. -Portal hypertension (high blood pressure) -Ascites-fluid in peritoneum GI bleeds (gastric and esoph) -Decreased Liver function tests and coag -
86
What can cirrohsis become?
hepatic encephalopathy or hepatocellular carcinoma
87
What are the Islets of Langerhans?
endocrine cells (pancreas
88
What is the difference between the pancreas' endocrine and exocrine function?
Endocrine: secreting dirctly into the bloodstream | Exocrine- excreting into a space
89
Which hormones are secreted by the pancreas into the blood stream?
``` insulin-beta cells-lowers glucose glucagon-alpha cells-raises glucose somastatin-delta cells-down regulation pancreatic polypeptide-multiple actions gastrin-from stomach normally, pathoogical if from pancreas. ```
90
What are acinar cells?
grape-like clusters that empty into ductal system. (pancreatic duct joins common bile duct.
91
What is secreted by the pancreas via its exocrine function?
Bicarbonate rich fluid via secretin | Digestive enzymes as proenzymes (zymogens)-under control of cck. zymogens do NOT WORK UNLESS ACTIVATED!!!!
92
List Pancreatic enzymes
Amylase-starch to glucose/maltose Lipase-Triglycerides to monoglycerides Proteases (trypsin,chmotrypsin, and elastase Nucleases Intestinal enterokinase-coverts trypsinogen to trypsin in pancreatic fluid and trypsin converts other zymogens
93
What is a proenzyme/zymogen?
``` A zymogen (or proenzyme) is an inactive enzyme precursor. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme. (wikipedia) ```
94
What is pancreatitis? | Causes?
Inflammation of pancreas due to autodigestion by enzymes. REfkux of bile/duodenal contents Alcoholism, biliary obstruction, EXTREME hyperlipidemia, hyperparathyroudism/hypercalcemia
95
Symptoms of pancreatitis?
Abd. pain, hypovolemia (intra abd fluid will increase and blood volume decrease), hypocalcemia (from lipolysis of peri pancreatic fat and soap precipitation.
96
In normal serum most amylase is not pancreatic, its ________.
salivary
97
What is amylase's obligate cofactor? | What color tubes to collect blood?
Calcium | serum tube or heparin plasma (green)
98
How is amylase measure?
Kinetically at 405-415 nm with artificial substrates. pancreatic amylase is measured by immunoinhibition of salivary enzyme.
99
High elevation of Amylase is more specific for pancreatitis. What else can casue elevations?
``` pancr. trauma gastritis-isoenzyme peptic ulcer-isoenzyme opiates ovarian cancer ectopic pregnancy renal disease Macroamylase (amylase +antibody)-not filtered by kidney-benign-PEG precipitate ```

Clinical Chemistry (9 decks)

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