Clinical Enzymology: Alkaline Phosphatase (ALP)

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Questions and Answers

What is the primary reason for the higher alkaline phosphatase (ALP) levels observed in boys during childhood?

  • Bone isoenzyme activity (correct)
  • Higher bone density
  • Increased liver isoenzyme activity
  • Higher levels of kidney isoenzyme

What effect does pregnancy have on alkaline phosphatase (ALP) levels?

  • Causes a two- to threefold increase primarily due to the placental isoenzyme (correct)
  • Increases ALP only in the liver isoenzyme
  • No significant effect on ALP levels during pregnancy
  • Decreases ALP slightly due to hormonal changes

Which factor is associated with an increase in alkaline phosphatase (ALP) levels?

  • High body mass index (correct)
  • Blood transfusion
  • Oral contraceptives
  • Cardiopulmonary bypass

What is the effect of fibric acid derivatives on alkaline phosphatase (ALP)?

<p>Decrease total ALP by 25% and liver isoenzyme by 40% (C)</p> Signup and view all the answers

How does smoking influence alkaline phosphatase (ALP) levels?

<p>Leads to a 10% average increase in total ALP levels (B)</p> Signup and view all the answers

What is the primary source of GGT found in serum?

<p>Hepatobiliary system (D)</p> Signup and view all the answers

In cases of biliary obstruction, how much can GGT levels increase compared to the upper reference limit (URL)?

<p>5 to 30 times (C)</p> Signup and view all the answers

What condition is NOT associated with increased GGT levels?

<p>Hyperthyroidism (A)</p> Signup and view all the answers

What is the correlation between GGT levels and body weight?

<p>GGT levels are higher in individuals with increased body weight (D)</p> Signup and view all the answers

Which factor does NOT contribute to increased GGT levels?

<p>Increased physical activity (C)</p> Signup and view all the answers

What is the primary role of alkaline phosphatase (ALP) in cells?

<p>Cleavage of phosphate-containing compounds (C)</p> Signup and view all the answers

What is the significance of GGT as a biochemical marker?

<p>Sensitive but not very specific for hepatobiliary disease (D)</p> Signup and view all the answers

Which enzyme isoform is primarily produced by osteoblasts?

<p>Bone ALP (C)</p> Signup and view all the answers

What increase in GGT activity is observed in infectious hepatitis?

<p>Moderate increase (two to five times the URL) (B)</p> Signup and view all the answers

Which of the following ions acts as an inhibitor of ALP activity?

<p>Phosphate ions (B)</p> Signup and view all the answers

In what situation might GGT levels be transiently increased?

<p>Drug intoxication (A)</p> Signup and view all the answers

Where is alkaline phosphatase predominantly located in hepatocytes?

<p>Canalicular surface (C)</p> Signup and view all the answers

Which of the following genes codes for the intestinal isoform of ALP?

<p>A gene on chromosome 2 (B)</p> Signup and view all the answers

What component is a constituent metal ion of ALP?

<p>Zn2+ (C)</p> Signup and view all the answers

What physiological function does the tissue-nonspecific isozyme of ALP primarily serve?

<p>Facilitating the movement of substances across membranes (B)</p> Signup and view all the answers

Which type of ALP is produced following the ingestion of fatty foods?

<p>Intestinal ALP (A)</p> Signup and view all the answers

What is the half-life of prostatic ACP?

<p>1 to 3 hours (C)</p> Signup and view all the answers

Which factor can lead to falsely low values for tartrate-resistant ACP (TRAP) activity?

<p>High bilirubin levels (A)</p> Signup and view all the answers

Why has the measurement of ACP become less popular for prostate cancer diagnosis?

<p>PSA has become the major serum test (D)</p> Signup and view all the answers

What condition is NOT associated with elevated levels of ACP?

<p>Chronic kidney disease (A)</p> Signup and view all the answers

Which of the following best describes the reference range for serum ACP?

<p>≤ 2 ng/mL (A)</p> Signup and view all the answers

What is the optimal pH range for NTP activity?

<p>6.6 to 7.0 (C)</p> Signup and view all the answers

What is a significant drawback of using ACP for prostate cancer screening?

<p>Sensitivity is inferior to PSA (D)</p> Signup and view all the answers

In which condition is serum NTP activity likely to be increased?

<p>Biliary cirrhosis (A)</p> Signup and view all the answers

What is the primary method used to separate isoenzymes of ACP?

<p>Electrophoresis (B)</p> Signup and view all the answers

Which statement is true regarding NTP and ALP activities?

<p>Increased NTP activity often indicates liver disease even with normal ALP. (B)</p> Signup and view all the answers

In which demographic does total and tartrate-resistant ACP levels typically increase?

<p>Women after menopause (B)</p> Signup and view all the answers

What are the normal reference intervals for NTP activity at 37°C?

<p>3 to 9 U/L (D)</p> Signup and view all the answers

What is the expected change in NTP activity in cases of infectious hepatitis?

<p>Moderately increased (A)</p> Signup and view all the answers

What is the primary clinical significance of measuring NTP activity?

<p>Identifying hepatobiliary diseases (A)</p> Signup and view all the answers

Which of these conditions might lead to increased serum NTP activity?

<p>Cholestasis from chlorpromazine (C)</p> Signup and view all the answers

How does NTP activity correlate with serum ALP in liver diseases?

<p>They may dissociate in liver diseases. (A)</p> Signup and view all the answers

What is the primary source of increased alkaline phosphatase (ALP) activity in serum during hepatobiliary disease?

<p>Hepatocytes (B)</p> Signup and view all the answers

Which isoenzyme of alkaline phosphatase has the shortest half-life?

<p>Intestinal isoenzyme (C)</p> Signup and view all the answers

What factor is responsible for the release of alkaline phosphatase from cells during liver injury?

<p>Increased cell membrane fragmentation (C)</p> Signup and view all the answers

Which condition is likely to cause a higher ALP activity due to extrahepatic obstruction?

<p>Obstructive jaundice from a gallstone (B)</p> Signup and view all the answers

What percentage of day-to-day variability is associated with the bone isoenzyme of alkaline phosphatase?

<p>20% to 25% (B)</p> Signup and view all the answers

Which forms of alkaline phosphatase are typically found in normal serum?

<p>Single form of ALP from liver or bone (C)</p> Signup and view all the answers

What is the approximate half-life of the liver isoenzyme of alkaline phosphatase?

<p>3 days (D)</p> Signup and view all the answers

In conditions of hepatobiliary disease, what types of ALP can be found in plasma?

<p>Both normal product and high molecular weight forms (D)</p> Signup and view all the answers

Flashcards

ALP in Children

The level of alkaline phosphatase (ALP) in the blood varies significantly based on age and gender. Specifically, ALP levels are generally higher in children, particularly boys, due to the presence of the bone isoenzyme.

ALP in Women After Menopause

After menopause, women experience a slight increase in their bone isoenzyme levels, which contributes to a rise in overall ALP levels.

ALP Levels During Pregnancy

During pregnancy, ALP levels significantly increase, typically two to three times the normal range. This rise is primarily attributed to the placental isoenzyme but also involves an increase in the bone isoenzyme.

ALP and Body Mass Index (BMI)

Obese individuals often exhibit higher ALP levels, with an average increase of approximately 10%, compared to those with a normal BMI.

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ALP and Medication

Certain medications, such as oral contraceptives and fibric acid derivatives, can influence ALP levels. Oral contraceptives tend to decrease ALP, while fibric acid derivatives reduce both total ALP and the liver isoenzyme.

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Alkaline Phosphatase (ALP)

A family of enzymes classified as hydrolases, primarily responsible for cleaving phosphate-containing compounds.

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Tissue-Nonspecific ALP Isozyme

The most abundant type of ALP found in the blood, produced in various tissues like the liver, kidney, and bone.

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Hepatic ALP

The ALP isozyme found in the liver, attached to the surface of cells near bile ducts.

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Bone ALP

The ALP isozyme found in bone cells responsible for the formation of new bone.

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Intestinal ALP

The ALP isozyme found in intestinal cells, released into the intestine after consuming fatty foods.

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Magnesium (Mg2+)

A mineral that activates ALP activity, along with other divalent ions like Co2+ and Mn2+.

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Inhibitors of ALP

Substances that inhibit ALP activity, preventing it from functioning properly.

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Examples of ALP Inhibitors

Inhibitors of ALP that include phosphate, borate, oxalate, and cyanide ions.

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What is Alkaline Phosphatase (ALP)?

Alkaline phosphatase (ALP) is an enzyme found in various tissues like liver, bone, intestines, and placenta.

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Explain the different forms of ALP in blood.

Different ALP forms exist, with varying origins and release mechanisms. For example, liver injury causes ALP synthesis to increase. Meanwhile, bile acids break down canalicular cell membranes, releasing ALP into the blood.

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How does serum ALP differ in health vs. hepatobiliary disease?

Normal serum typically shows one type of ALP, from liver or bone. However, hepatobiliary disease can lead to different ALP forms, both normal and those attached to lipoproteins.

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Explain the role of intestinal ALP.

The intestinal isoenzyme of ALP is released into the duodenum after a meal, entering lymphatic fluid.

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What are the half-lives of different ALP isoenzymes?

ALP isoenzymes have varying half-lives, affecting their persistence in the blood. For example, intestinal ALP has a short half-life, while liver ALP lasts longer.

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Explain the daily variability in total ALP.

Day-to-day fluctuations in total ALP are normal, but bone ALP can vary significantly.

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What are the primary sources of elevated serum ALP?

Increased ALP activity in serum typically originates from the liver or bone.

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Explain how biliary obstruction affects ALP levels.

Biliary obstruction, whether extrahepatic or intrahepatic, triggers increased ALP synthesis by liver cells. Extrahepatic obstruction usually results in higher ALP levels compared to intrahepatic obstruction.

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Acid Phosphatase (ACP) Test

A blood test used to measure the activity of the enzyme acid phosphatase (ACP).

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Acid Phosphatase (ACP)

A group of enzymes that break down phosphate compounds., primarily found in the prostate, bones, and liver.

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Elevated ACP Levels

ACP levels are elevated in conditions affecting the prostate, such as prostate cancer and benign prostatic hyperplasia.

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Prostatic Acid Phosphatase (PAP)

The enzyme produced in the prostate gland and responsible for the breakdown of phosphate compounds.

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Prostate-Specific Antigen (PSA)

A faster and more reliable blood test for prostate cancer compared to ACP.

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Urinary and Serum Prostatic Acid Phosphatase

Prostatic ACP can be detected in the blood and urine. High levels are associated with prostate cancer.

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Benign Prostatic Hyperplasia (BPH)

Prostate enlargement that is not cancerous and can cause urinary problems.

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Prostatic Infarction

An inflammatory condition in the prostate that can cause elevated ACP levels.

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What is the optimal pH for 5NT activity?

The optimal pH level for 5'-Nucleotidase (5NT) activity is between 6.6 and 7.0.

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Where is 5NT found in the body?

5NT is an enzyme that is ubiquitously found in the body, particularly in the liver and other tissues.

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What does elevated 5NT levels in the blood suggest?

Elevated serum 5NT activity is a strong indicator of hepatobiliary disease, hinting at problems with bile secretion.

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What can cause elevated 5NT levels?

Increased 5NT activity can result from both extrahepatic factors (e.g., blockage outside the liver) and intrahepatic factors (e.g., cholestasis within the liver).

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How does 5NT activity change in parenchymal cell damage?

In cases of parenchymal cell damage, such as infectious hepatitis, serum 5NT levels are only moderately increased compared to other hepatobiliary conditions.

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Why is measuring 5NT alongside ALP helpful?

Measuring 5NT activity in addition to total ALP can help distinguish between different causes of elevated ALP, especially in hepatobiliary disease.

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Why is 5NT a useful diagnostic marker?

5NT is a useful diagnostic marker because its activity often increases when liver ALP is normal, suggesting underlying liver disease.

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What is the normal reference range for 5NT activity?

The normal range for 5NT activity in the blood is between 3 and 9 units per liter (U/L), and there is no difference between men and women.

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GGT and Hepatobiliary Disease

Increased GGT activity is often associated with the presence of hepatobiliary disease, a condition affecting the liver and bile ducts. However, the enzyme's lack of specificity can limit its diagnostic value, making it difficult to pinpoint the exact cause of the liver problem.

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GGT in Biliary Obstruction

GGT levels rise significantly in individuals with obstructive conditions within the liver or bile ducts (posthepatic), such as gallstones or tumors blocking bile flow, reaching 5 to 30 times the normal reference range.

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GGT in Liver Cancer

Elevated GGT levels are seen in patients diagnosed with primary or secondary liver cancer (metastases), suggesting an obstruction within the liver due to tumor growth.

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GGT in Hepatitis

A moderate elevation of GGT, with levels 2-5 times the reference range, is typical in cases of viral hepatitis, indicating inflammation and damage to the liver.

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GGT in NAFLD

Over 50% of individuals with NAFLD (non-alcoholic fatty liver disease) exhibit a moderate increase in GGT levels. These elevations, while usually small, can be fleeting and are also observed in cases of drug toxicity.

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GGT in Pancreatitis

GGT levels can increase 5 to 15 times the normal range in acute or chronic pancreatitis, especially when the pancreas is also affected by blockage in the bile ducts.

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GGT and Alcohol

Patients with alcoholic hepatitis, characterized by liver inflammation caused by excessive alcohol consumption, often exhibit high GGT levels. Additionally, heavy drinkers generally have elevated GGT, even without obvious liver disease.

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GGT and Obesity

GGT levels tend to rise with increasing body weight and obesity. Moreover, alcohol's impact on GGT is more pronounced in overweight or obese individuals.

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Study Notes

Clinical Enzymology

  • This topic covers clinical enzymology, a subfield of clinical biochemistry.

Alkaline Phosphatase (ALP)

  • ALP is a type of hydrolase enzyme.
  • Multiple genes code for different ALP isoforms.
  • Their physiological role isn't fully understood.
  • Tissue-nonspecific isozyme is abundant in the kidney, liver, and bone.
  • Post-translational modifications lead to different carbohydrate side chains in various tissues.
  • Two other genes on chromosome 2 code for placental and intestinal ALP isoforms.
  • Another gene codes for a germ cell/placental-like isoenzyme with similar properties to the placental isoenzyme.
  • The enzyme is primarily bound to cell membranes, involved in phosphate cleavage, and facilitating substance transport.
  • Hepatocytes produce ALP attached to the canalicular surface.
  • Osteoblasts produce bone ALP, involved in pyrophosphate cleavage (an inhibitor of bone mineralization).
  • Intestinal epithelial cells produce intestinal ALP, released after fatty food ingestion.
  • Divalent ions like Mg2+, Co2+, and Mn2+ are ALP activators.
  • Zn2+ is a constituent metal ion.
  • Ions like phosphate, borate, oxalate, and cyanide are potent inhibitors.
  • Diverse release mechanisms of ALP from cells result in various plasma forms.
  • In liver injury, ALP synthesis increases.
  • Bile acids dissolve canalicular membrane fragments.
  • Normal serum typically has a single liver or bone form of ALP.
  • Hepatobiliary disease shows both normal and attached membrane form ALP.
  • Intestinal isoenzyme is released into duodenal fluid and lymphatic fluid after meals.
  • ALP isoenzyme half-lives differ: intestine(minutes), bone(1 day), liver(3 days), and placenta(7 days).
  • Day-to-day variation in total ALP is 5-10%, while bone isoenzyme shows 20% variability.
  • Different locations of ALP in the body: liver (low in liver, high in biliary tree), intestine (renal tubular cells), placenta, and bone (osteoblast).
  • ALP increases in serum are from liver or bone.
  • Hepatobiliary disease and bone disease are ALP activity sources.
  • Obstruction of biliary tracts causes ALP synthesis to increase by 10-12 times.
  • Other sources of elevated serum ALP include advanced primary liver cancer, widespread secondary hepatic metastases, liver disease primarily affecting parenchymal cells, and primary biliary cirrhosis.
  • Increased ALP is observed in pregnancy (up to two to three times URL).
  • Benign transient ALP increases can be in infants and children.
  • Carcinoplacental isoenzymes (like Regan isoenzyme) result from placental ALP gene de-repression.
  • Different tumor types produce modified non-placental isoenzymes (like Kasahara isoenzyme).
  • Increased osteoblastic activity (Paget disease, osteosarcoma, bone metastases, metabolic bone disease) elevates bone isoenzyme.

5'-Nucleotidase (5NT)

  • 5' -Nucleotidase an enzyme acts only on nucleoside-5'-phosphates, releasing inorganic phosphate.
  • Widely distributed in tissues, localized in cell membranes,
  • pH optimum is between 6.6 and 7.0.
  • Serum NTP activity appears to reflect hepatobiliary disease with high specificity (increases 3-6 fold).
  • Elevated NTP is due to extrahepatic or intrahepatic conditions interfering with bile secretion.
  • Serum NTP activity may be normal in approximately half of individuals with elevated liver ALP.
  • Increased NTP in normal liver ALP suggests liver disease.

É£-Glutamyltransferase (GGT)

  • GGT catalyzes the transfer of the γ-glutamyl group from peptides to acceptors.
  • It acts only on peptides with a terminal glutamate residue.
  • Found high in proximal renal tubule, liver, pancreas, and intestine.
  • The enzyme is cytoplasmic and present in cell membranes, potentially transporting amino acids/peptides.
  • Crucial for maintaining adequate intracellular glutathione (antioxidant).
  • Serum GGT activity comes mainly from the liver, commonly rising in various forms of liver disease.
  • Elevated in most subjects with liver illness, regardless of the cause.
  • In biliary obstruction, GGT increases 5-30 times its upper reference limit (URL).
  • Increased GGT is also found with increased body mass index, alcohol use, pregnancy, and anticonvulsant treatment.
  • GGT activities show an independent prognostic value for cardiovascular morbidity and mortality, and have redox/pro-oxidant reactions in cell.

Acid Phosphatase (ACP)

  • ACP is a hydrolase enzyme breaking down phosphate monoesters.
  • All ACPs show optimal activity below pH 7.0.
  • High concentration locations include prostate, liver, spleen, erythrocytes, and bone.
  • Multiple forms with various molecular weights and tartrate sensitivities exist (e.g., lysosomal, prostatic, erythrocytic, macrophage, osteoclastic), crucial in bone remodeling.
  • Serum ACP concentration is low, and erythrocyte ACP is differentiated from other types by inhibiting it with substances.
  • A specific isoform of tartrate-resistant acid phosphatase (TRAP or TRAPase) is commonly found in osteoclasts and used to measure bone remodeling.
  • A type of TRAP called TRAP-5b is of crucial interest, acting in bone remodeling.
  • Serum ACP values depend on factors like age, gender, and hormone levels.
  • Total ACP and tartrate-resistant ACP are higher in children.
  • In women, total and tartrate-resistant activities increase after menopause.
  • Prostatic ACP has a 1-3 hour half-life.
  • ACP assays rely on hydrolysis to produce a measurable compound.
  • Elevated ACP associated with prostate disease, though PSA is the primary test for it.
  • Other potential causes include prostatic hyperplasia, malignancy, and urinary issues.
  • Clinical conditions like prostatic massage, inflammation, infarction, and procedures like biopsies can lead to temporary increases.
  • In suspected rape cases, vaginal fluid ACP provides a possible indicator.

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