CAPÍTULO IV. Obtención y estudio de los conjuntos de datos
IV.3. Selección y estudio de los conjuntos de datos para experimentación
of UDP-GT Severe, hyperbilirubinaemia in
neonate total bilirubin 20-50 mg/dl
Total bilirubin < 20 mg/dl
Causes Kernicterus The condition depends on the level of enzyme reduction.
Gibert, although unconjugated, is usually detected in adolescence Dubin Johnson and Rotor’s syndromes cause conjugated
hyperbilirubinemia.
112. In precore HBV all true except: Probable answer: HBeAg positive
A precore mutant is a variety of hepatitis B virus that does not produce hepatitis B virus e antigen (HBeAg).
These mutants are important because infections caused by these viruses are difficult to treat, and can cause infections of prolonged duration and with a higher risk of liver cirrhosis.
The HBV has four genes:
S Codes for HBsAg
P Codes for DNA polymerase C Codes for HBeAg and HBcAg
Has precore (produces HBeAg) and core region (produces HBcAg) X codes for HBxAg which may be involved in carcinogenesis Precore mutants are readily detectable by HBV DNA in serum, but hepatitis B e antigen (HbeAg) is absent. The X gene.[6]
Liver
- Used for diagnosing acute infection or detecting carriers.
- First viral marker to appear during acute infection.
- Its persistence >6 months typically characterizes the state of chronic carrier.
- Its presence indicates that a person is infectious.
HBsAb or anti-HBs (protective, neutralizing Ab) - A marker of recovery or immunization.
- Its presence, in absence of other +ve serologies, is seen in successfully immunized individuals.
anti-HBc:
- A combination of IgG and IgM antibodies.
- It develops in all HBV infections and indicates infection at some undefined time in the past.
- It generally persists for life, - Not a marker for acute infection, - Does not develop from vaccine.
IgM anti-HBc:
- Appears in persons with acute disease and tends to disappear several weeks after initial exposure.
- A marker of acute infection although it can also be seen during flares or exacerbation of chronic HBV.
HBeAg (marker of replication and infectivity):
- Its absence does not ensure that there is no replication or infectivity as in the precore mutant strain of HBV, which does not produce HBeAg, but it still successfully replicates.
HBeAb or anti-HBe: Appears when infected
individuals lose HBeAg (seroconversion). This is often associated with the disappearance HBV DNA in serum and remission of liver disease.
HBV DNA (marker of replication and infectivity).
- Can be detected and quantified by using a nucleic acid test (NAT).
- Used to determine the need for treatment and to assess the response to therapy.
Interpretation of the Hepatitis B Panel HBsAg
Immune due to natural infection
Immune due to hepatitis B vaccination
1. Recovering from acute HBV infection.
2. Distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum.
3. Susceptible with a false-positive anti-HBc.
4. Undetectable level of HBsAg present in serum and the patient is actually a carrier.
113. severity of chronic liver disease is indicated by
a. S. albumin b. ALP c. GGT
Probable answer: a. Serum albumin
S. Albumin: a marker for synthetic function of the liver; it is valuable guide to the severity of chronic liver disorders. Low S. albumin is bad prognostic sign.
114. Feces gets its brown pigmentation from_____.
a. stecobilirubin b. stercobilin c. stercobilinogen d. stecobilin
Probable answer: d.stercobilin
Conjugated bilirubin is excreted in urine as urobilinogen, giving urine its color.
In the intestine, bilirubin is converted by bacteria to stercobilinogen.
Stercobilinogen is oxidized to stercobilin, which is responsible for the pigmentation of feces.
115. In a hemolytic crisis, bilirubin is:
a. normal b. increased c. decreased d. unchanged
Probable answer: Increased.
Enzymes
C
hemistryEnzymes
116. Hyperamylasemia not a feature of
a. Acute pancreatitis.
b. Cerebral trauma.
c. Cystic fibrosis.
d. Intestinal obstruction.
e. Perforated peptic ulcer.
Probable answer: Cystic fibrosis Hyperamylasemia occurs in:
1. Acute pancreatitis: within 2 hours, peak 12-72 hrs and ↓4days.
The increase is not corresponding to severity, but the higher the level the higher the probability of pancreatitis.
2. Complications of acute pancreatitis: Persistantly high amylase pseudocyst of pancrease.
3. Other causes of acute abdomen:
Appencdicitis Intestinal obstruction Peptic ulcer perforation Peritonitis.
Salpingitis, ectopic pregnancy
4. Salivary fraction: in parotitis, mumps, calculi etc.
5. Renal insufficiency due to excretion.
6. DKA.
7. Addicts spasm of sphincter of Oddi.
Other causes of hyperamylasemia include pneumonia (↑salivary amylase), cerebral trauma (activate pathways that increase amylase levels in the blood, suggesting a central nervous system regulation of serum amylase levels), burns, abdominal aortic aneurysms (increased pancreatic amylase), drugs (increased salivary and/or pancreatic amylase), anorexia nervosa and bulimia (increased salivary amylase), nonpathologic (increased salivary and/or pancreatic amylase), and organophosphate poisoning
In Cystic fibrosis, blood levels of amylase may rise when mucus blocks the pancreatic ducts from carrying the enzymes that the small intestine needs to digest food properly.
117. An enzyme that is located exclusively in cytoplasm is:
a. Acid phosphatase.
b. AST
c. Glutamate dehydrogenase.
d. Isocitrate dehydrogenase e. LDH.
Probable answer: LDH or ALT
A mild, reversible viral inflammation of the liver is likely to increase only the permeability of the cell membrane and allow cytoplasmic enzymes to leak into the blood.
A severe attack causing cell necrosis also disrupts the mitochondrial membrane, and both cytoplasmic and mitochondrial enzymes are detected in blood.
Thus knowledge of the intracellular location of enzymes helps to determine the nature and severity of a pathological process if suitable enzymes are assayed in the blood.
Acid phosphatase is present in lysosomes, which are organelles present in all cells with the possible exception of erythrocytes.Extra lysosomal ACPs are also present in many cells.
CK: there are 3 cytosolic isoenzymes (CK-3, CK-2, CK-1) and one mitochondrial isoenzyme (CK-Mt)
Glutamate dehydrogenase: glutamic dehydrogenase is found in the nucleus as well as in the cytoplasm (at 60% of the cytoplasmic level).
LDH activity is present in all cells of the body and is invariably found only in the cytoplasm of the cell.
AST: both mitochondria1 and cytoplasmic forms are found in cells.
GGT is present in cytoplasm (microsomes), but the larger fraction is located in the cell membrane.
ALT is exclusively cytoplasmic;
Isocitrate dehydrogenase is found in the cytoplasm and peroxisomes.
- enzymes that catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate.
Enzymes
C
hemistry- Belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+).
- Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent IDH, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic.
- Each NADP(+)-dependent isozyme is a homodimer.
- The protein encoded by the IDH2 gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria.
- It plays a role in intermediary metabolism and energy production.
This protein may tightly associate or interact with the pyruvate dehydrogenase complex.
NTP is a glycoprotein widely distributed throughout the tissues of the body and is principally localized in the cytoplasmic membrane of the cells in which it occurs
118. In acute abdomen all can occur except:
a. Hypoamylasemia
Hyperamylasemia: occurs in
- 70-75% of cases of acute pancreatitis (the higher the more probable the diagnosis), however, isoenzymes and urine amylase are more specific than the total and serum amylase respectively.
- parotitis,
- renal insufficiency (↓excretion)
- other causes of acute abdomen e.g. appendicitis, intestinal obstruction, peptic ulcer perforation, peritonitis, salpingitis or ectopic pregnancy.
Hypoamylasemia may occur in chronic pancreatitis associated with irreversible damage to pancreas.
119. The enzyme with shortest half life:
a. LD5.
b. ALT.
c. Intestinal ALP.
Probable answer: AST then ALT or CK then LD
Clearance of enzymes from plasma occurs at variable rates.
The half life of an enzyme causes variation in the duration of elevation of the enzyme after release in the circulation. So, roughly to answer such a question, remember which enzyme disappears earliest among the profile and which disappears last e.g. CK has a shorter half life than LDH,
More precisely:
- The half-life of ALT is 47 hours,
- The half-life of cytosolic AST is 17 hours; thus although more AST is released from liver, the much longer half-life of ALT leads to higher activities of ALT than AST in most forms of hepatocellular injury.
- The half-life of the liver isoenzyme of ALP is from 1 to 10 days; the former figure appears to correspond better to the changes seen with removal of gallstones.
- The half-life of GGT is 4.1 days.
- The half-life of CK-MB in the circulation is relatively short (approximately 12 hours)
120. The enzyme needed in biological systems for joining two molecules is called:
a. Lyases b. Diastases c. Polymerases d. Hydrolase
Classification of enzymes:Enzyme commission (EC) classification:
1. Oxidoreductases: (dehydrogenases or oxidases) AH2 + B A + BH2
a. Aerobic oxidases: (use oxygen as H2 acceptor) AH2 + O H2O + A e.g. tyrosinase and cytochrome oxidase.
b. Aerobic dehydrogenases: (H2O2 is formed) AH2 + O2 H2O2 + A e.g. glucose oxidase.
c. Anaerobic dehydrogenase: (need coenzyme acceptor) AH2 + coenzyme coenzyme H2 + A e.g. LDH need NAD, G-6-PD need NADP.
Importance: of particular importance in:
a) Direct diagnostic value.
Enzymes
C
hemistryb) Coupling reactions: Dehydrogenases can be used as indicator enzymes for measuring activities of other enzyme which do not involve oxidation or reduction.
2. Transferases: transfer a group from one compound to another e.g. Aminotransferases AST, ALT transfer amino group.
Phosphotransferases CK transfer phosphate group.
3. Hydrolases: Hydrolyze the substrate.
A-B + H2O AH + BOH According to their substrates they include:
a. Hydrolases acting on esters: Lipase, choline esterase, phosphatases, ALP, ACP,5-nucleotidase,glucose-6-phosphatase.
b. Hydrolases acting on glycosyl compounds: -amylase.
c. Hydrolases acting on peptide bonds: Pepsin.
d. Hydrolases acting on C-N bond: e.g. urease.
4. Lyases: Remove a chemical group from substrate by mechanism other than hydrolysis e.g. aldolase.
5. Isomerases: Inter-convert optical isomers e.g. racemases and epiderases.
6. Ligases: (synthases): Link 2 molecules together and need ATP e.g.
acetyl-co-A synthase.
NB:
Polymerases: are enzymes that catalyse the synthesis of a polymer, esp the synthesis of DNA or RNA.
Diasterases: are enzymes that break down starch into maltose and dextrose.
121. Which of the following enzymes is most specific for diagnosis of a Myocardial Infarction?
a. AST b. LD c. Troponin.
d. CK
Probable answer: CK (being an enzyme) or Troponin (being most specific)
Biochemical markers of myocardial injury:
1. Aspartate aminotransferase: was considered as a very good marker of cardiac injury as it was found to be normal in pulmonary embolism acute abdominal conditions and other heart conditions such as angina and pericarditis. But later on, its use become limited due to its elevation in trauma to skeletal muscles and liver diseases 2. Lactate dehydrogenase and its isoenzyme LD1: The prolonged
elevation makes it a good marker for those patients admitted to the hospital after several days of MI. However, its use is discouraged due to its non-specificity as its increased levels are found in progressive muscular dystrophy, myoglobinuria, leukaemia, pernicious anaemia, megaloblastic and hemolytic anaemia, renal disease and in generalized carcinoma 3. Creatine kinase and its isoenzyme MB: its presence in large
amounts in skeletal muscle and increased levels found in muscular dystrophy, hypothyroidism, hypothermia, alcoholism,
cerebrovascular accidents and a variety of myopathies make it unsuitable as a marker of myocardial injury.
Recently, the measurement of mass concentration of CKMB has increased its sensitivity and specificity enabling tomeasure small changes during the early hours following MI
4. Myoglobin: a 18 KD cytosolic protein, appears in blood earlier after myocardial injury than any other marker available so far. However, it is not cardiac specific as its release from the skeletal muscles cannot be distinguished from that released due to cardiac injury (36) and it is found to be elevated in severe renal insufficiency and
Enzymes
C
hemistryin patients being on alcohol.
5. Cardiac Troponins: a protein complex located on the thin filament of striated muscles consisting of the three subunits namely Troponin T (TnT), Troponin I (TnI) and Troponin C (TnC). Of the three troponins, TnT and TnI are being used as the biochemical markers for the diagnosis of myocardial injury. The troponins found in cardiac tissue (cTn) have a different amino acid sequence than that present in troponin of skeletal muscles. This makes cTnT and cTnI more specific for the diagnosis of myocardial injury.
cTnT and cTnI are now regarded as the most specific biochemical markers of myocardial injury.
122. ALP is elevated in the following disorder?
a. Addison's Disease.
b. Paget's Disease c. Diabetes Insipidus d. Scleroderma
Probable answer: b. Paget’s disease.
The highest levels of ALP (10-25 times the URL) are encountered in Paget’s disease as a result of the action of the osteoblastic cells as they try to rebuild bone that is being resorbed by the uncontrolled activity of osteoclasts
123. The "MM" fraction of CK is most abundant in _____z
a. Skeletal muscle b. Cardiac muscle c. Brain tissue d. none of the above
Probable answer: Skeletal muscle
According to the type of subunits, CK has 3 isoenzymes:
1. CK1 (BB): Specific for the brain. The fastest in electrophoresis and moves towards the anode.
2. CK2 (MB): Specific for myocardium. Normally, CK-MB activity is <
5U/L and accounts for <3% of total CK activity.
3. CK3 (MM): Most abundant in skeletal muscles. The slowest in electrophoresis and moves toward the cathode.
4. CK-Mit: Mitochondrial isoenzyme. Constitutes 15% of cardiac CK and is found in adults with severe illness and children with myocardial diseases.
124. What is enzyme is more specific for acute pancreatitis?
a. AST b. Amylase c. GGT d. Lipase
Probable answer: d. Lipase.
The two enzymes of pancreatic origin are:
a. Amylase
Not specific for acute pancreatitis.(70-75%)
Isoenzymes are of higher specificity.
Urine amylase is more specific than serum amylase b. Lipase:
More specific and sensitive than amylase.
Simultaneous measurement of lipase and amylase 90%
specificity