Enzymes of importance to Disease States

Question 1

what is elevated in all forms of cholestasis and especially obstructive jaundice? In what other conditions may it be elevated?

Answer 1

alkaline phosphatase, ALP; in skeletal disease including Paget’s, hyperparathyroid, fractures, bone tumors, and also during accelerated bone growth in kids

Question 2

what would indicate a hepatocellular vs a cholestatic pattern on LFT analytes?

Answer 2

greater aminotransferase proportion to ALP, so increased AST or ALT

Question 3

What conditions would cause ALT to predominate over AST if the condition is hepatocellular and not obstructive? What conditions are associated with more significant AST over ALT?

Answer 3

ALT is more specific for liver cell damage: acute or chronic hepatitis, steatohepatitis, cirrhosis,
AST is higher in 6 to 8 hours post AMI so is useful for ruling out concurrent liver damage, but it also is higher in musculoskeletal (like dystrophy) and pulmonary in which ALT is not as elevated

Question 4

What enzyme would predominate in hepatocellular disease involving alcohol damage?

Answer 4

AST, aspartate transaminase

Question 5

what analyte is most commonly used to evaluate kidney function?

Answer 5

BUN, blood urea nitrogen

Question 6

what is azotemia?

Answer 6

elevation of nitrogenous productswith BUN usually elevated between 7 to 21 mg/dL, creatinine in blood and other waste products in blood

Question 7

azotemia/ elevated BUN can be prerenal, renal, or postrenal. GIve some causes of prerenal

Answer 7

cardiac decompensation, increased dietary protein or increased protein catabolism, or dehydration, or loss of blood flow to kidney such as in lower blood volume, shock…

Question 8

some causes of renal azotemia/elevated BUN

Answer 8

acute glomerulonephritis, chronic nephritis, polycystic kidney, nephrosclerosis, tubular necrosis

Question 9

causes of post-renal azotemia?

Answer 9

obstructions such as kidney stones, enlarged prostate, tumors…

Question 10

what ratio is often used instead of BUN for kidney function eval? what could cause a low ratio?

Answer 10

serum BUN to creatinine ratio; low protein intake, starvation, severe liver disease

Question 11

Causes of high BUN to creatinine when creatinine normal?

Answer 11

catabolism of tissues, pre-renal azotemia, high protein intake

Question 12

When in particular would AST be elevated? how many isoenzymes and which are elevated in what cases?

Answer 12

after an MI, or in hepatobiliary disease such as viral hepatitis, cirrhosis. The mitochondrial is only present in disease states; Cytoplasmic is found in normal serum

Question 13

what is the more liver-specific enzyme and basic test principle?

Answer 13

Alanine aminotransferase, ALT. Like with AST, it is quatifies by using it on a substrate, then using the product of this (pyruvate here, but oxaloacetate for AST) to see a decrease in absorbance when NADH is oxidized

Question 14

give approximate reference ranges for BUN and creatinine

Answer 14

BUN (urea): 8 to 24 mg/dL ( 7 to 20 another source; 2.5- 7 mmol/L)
Crea: 0.8 to 1.3mg/dL

Question 15

how is creatinine clearance calculated (give formula) and what is an average range?

Answer 15

Urine crea/ serum crea x urine vol in ml/min for 24 hours x 1.73/ BSA

differs btw M/F and by age but generally 95 to 105 +/- 20 mL/min/1.73 m^2

Question 16

what is the clin sig of incrsd or dcrsd uric acid? ref range?

Answer 16

increased in gout, renal disorders, lead poisoning, lactic acidosis (plus other)
decrsd in severe liver disease, tubular reabsorption disorders
F 2.6 -6, M 3.5 to 7.2 mg/dL…..think 3 to 7

Question 17

what causes blood levels of ammonia to increase?

Answer 17

severe hepatocyte dysfunction, as they are supposed to convert it to urea bc ammonia is neurotoxic

Question 18

how must a specimen for ammonia be handled?

Answer 18

on ice immed, collected in EDTA, centrifuge w/in 20 mins and remove plasma

Question 19

what are lactate dehydrogenase isoenzymes differentiated by?

Answer 19

their constituent subunits, of combos of M (muscle/liver) polypeptides and H (heart) polypeptides

Question 20

what are the groupings of LD isoenzymes associated with clinically (3 main groupings)

Answer 20

LD 1 and 2: AMI and RBC destruction—> bleeding hearts are #1!
LD3: pulmonary, pancreatitis, lymphocytosis
LD 4 and 5: liver and skeletal muscle—> dancing alcoholic

Question 21

what isoenzyme of CK and what % of total CK is suggestive of AMI? what test will also be performed is suspected heart attack?

Answer 21

CK-MB at >6% ; a troponin assay

Question 22

what is y-glutamyltransferase used to evaluate and how does it compare to other enzymes that may also elevate?

Answer 22

liver/bile duct disease (intra and post obstruction can cause levels 5 to 30X over ref range); bc it elevates first and stays high longer than ALT, AST and ALP: it is the more sensitive assay of hepatobiliary disease

Question 23

does GGT elevate in bone disease? what does?

Answer 23

no; ALP

Question 24

what test is highly specific for pancreatic disease and what is it often used in conjunction with? how quickly does it elevate, peak and stay elevated?

Answer 24

Lipase, often assayed with amylase; Lipase increases in 4 to 8 hours, peaks at 24, lasts 8 to 14 days (amylase rises faster and disappears in 3 days or so)

Question 25

why would you test for G6PD ?

Answer 25

a deficiency (an X-linked genetic disorder) can cause drug-induced (or Fava bean!) hemolytic anemia, esp with antimalarial drugs; also infection can cause this anemia bc the enzyme is supposed to protect cells from oxidative damage by producing NADPH which donates electrons to glutathione to neutralize ROS, but there won’t be enough for the increased demands of infection

Question 26

What is troponin? what are the two types we measure and when do they elevate?

Answer 26

contraction-calcium-regulating proteins found in heart and skeletal muscle that rise in serum following damage; Troponin I of 1.0 ug + or Troponin T of 0.1 ug or higher is considered significant

Question 27

what biomarker for MI is an early marker rising within 1 to 2 hours of symptom onset and effective for rule out within the 2 to 6 hour window after, but is not cardiac specific (can be higher in trauma, muscle injury, renal failure)…?

Answer 27

Myoglobin

Question 28

What are the 3 forms of natriuretic peptides? what are their functions?

Answer 28

ANP, BNP, and CNP

They promote excretion of sodium and water by increasing GFR and decreasing tubular reabsorption of sodium

Question 29

What is the clinical significance and mechanism of BNP release/ function?

Answer 29

BNP is brain natriuretic peptide that is secreted by HEART ventricles when ventricles experience volume expansion and incrsd pressure; the BNP dilates vessels and promotes salt and water loss in order to reduce fluid load on the heart

Question 30

In what disease particularly is BNP increased and how assayed? ref range>

Answer 30

CHF; fluorescence and chemiluminescent assays.

<100pg/mL

Question 31

what is proBNP? advantages to measuring vs BNP?

Answer 31

the inactive N-terminal that is cleaved off when BNP is activated; it is not affected by nesiritide administration, which treats CHF, so can be measured then, whereas BNP can’t in that situation

Question 32

what type of protein is CRP? what is it used for?

Answer 32

it’s a B-globulin, an acute phase reactant; used to help predict cardio risk although levels increase not only in AMI but inflammation, infection, stress and trauma

Question 33

what are the levels of risk in CRP assays?

Answer 33

low is <1.0 mg/L
med is 1.0 to 3.0
high is >3.0 mg/L

Question 34

what does measurement of homocysteine help indicate?

Answer 34

arterial inflammation; elevated levels cause damage to arterial walls leading to plaque formation

Question 35

List markers for hepatocellular necrosis versus cholestasis; as well as other tests of liver function

Answer 35

1. hepatocellular necrosis: ALT (mst specific for liver cell), AST, and LD especially LD 4 and 5.
2. cholestasis: ALP, GGT
3. Other: bilirubin (total, direct/conj, indirect/unconj), ammonia, albumin, AFP

Question 36

the functioning of the liver can be evaluated based on its ability to produce? give 2 answers

Answer 36

albumin and vit-k dependent clotting factors

Question 37

what do aminotransferases (AST and ALT) out of proportion to ALP suggest for a differential diagnosis?

Answer 37

hepatocellular disease

Question 38

what would an elevated ALP, GGT and bilirubin in higher proportion over aminotransferases suggest?

Answer 38

cholestatic disease (obstructions) and also nonhepatic disorders such as bone (ALP esp)

Question 39

would AST or ALT be higher in cases of AMI, AMI w/ concurrent liver damage, alcoholic cirrhosis, and even pulmonary embolism?

Answer 39

AST

Question 40

what aminotransferase is more specific for liver disease?

Answer 40

ALT

Question 41

If liver function is normal and albumin is low, what are some causes?

Answer 41

malnutrition (poor protein intake) or protein loss such as through nephrotic syndrome, malabsorption…

Question 42

where is the highest concentration of acid phosphatase, ACP?

Answer 42

the prostate; it is also in bone and spleen, RBCs and pltlts

Question 43

what drugs will increase GGT levels?

Answer 43

phenytoin and phenobarbital

Question 44

in contrast to ALP, how are GGT levels in bone disease and pregnancy?

Answer 44

normal