Random Questions Flashcards
1
Q
Tests performed at PMH Chem Toxicology (>4,13)
A
SPE for MM
Urine CAT (Strip pH<2>5 cancel, LC-MS, sample preparation: Column extraction)
Urine Toxic (sample preparation: dilution)
Urine Myoglobin (CK<200 / >23000 cancel, Strip HB+ cancel,rhabdomyolysis)
Cryo (1:IgM MM;2:Infection[HepC],3:Autoimmune[SLE,RA])
Urine 5-HIAA & HVA (Neuroblastoma,carcinoid tumors)
Plasma acylcarnitine (fatty acid oxidation)
Urine Metabolic profiling (LCMSMS)
Urine Sulfite (sulfite oxidase deficiency)
Urine Chyle (lymphatic obstruction)
Urine Mucopolysaccharide (E, MPS1, Hurler’s syndrome)
Urine Porphobilinogen / Porphyrin(HPLC) / Urobilinogen (porphyrias / heme production)
Urine reducing substance (galactosemia)
2
Q
Organs involved in Vitamin D synthesis & analytical utility of 25OH & 1,25 OH (2)
A
Skin, Liver, Kidney
25OH for vitamin D deficiency / excess
1,25OH for sarcoidosis
3
Q
Test to differentiate osteoporosis from osteomalacia & discuss VDDR vs VDRR (2)
A
ALP
VDDR:
1 alpha hydroxylase deficiency (Liver, vitD Low)
vitD R deficiency (Bone, vitD High)
VDRR:
PHOS reabsorption deficiency (CA normal, PHOS Low)
4
Q
Reference range of GLU, 4 diagnostic criteria for DM & OGTT for GDM (6)
A
3.9–5.5
- fasting GLU >7 * 2 [5.5~7 = IFG]
- random GLU >11 + polyuria / increased thirst / weight loss
- 2h 75g OGTT >11 [7.8~11 = IGT]
- HbA1C>=6.5%
GDM screening
1h 50g OGTT >7.8
GDM confirmatory
1. 3h 100g OGTT
-fasting GLU>5.5
-1h >10
-2h >8.6
-3h >7.8
[Any 2]
2. 2h 75g OGTT
Same cutoff as 3h OGTT
5
Q
Why use HK+G6PD rather than GO, how POCT differs in terms of assay & interference (4)
A
Although GO is more specific, H2O2 is prompt to interference, so use HK+G6PD
POCT is amperometric and uses either GDH (FAD+/NAD+/PQQ) or GO (H2O2).
As POCT uses whole-blood, high HCT causes falsely low result, bias can be corrected by measuring sample conductivity
6
Q
Name 5 hormone which affects glucose level & the mechanism behind the effect (10)
A
Insulin:
Glucose uptake, Lipid & Glycogen synthesis, X Glucose synthesis
GH & Cortisol:
Glucose synthesis
EPI:
Glycogen breakdown
Glucagon:
Both Glucose synthesis & Glycogen breakdown
7
Q
Why are we doing C-peptide, Insulin, Urine mucopolysaccharide, Urine reducing sugar, and D-xylose absorption test (5)
A
C-peptide: exogenous insulin source
Insulin: insulinoma, Reactive hypoglycemia
Urine mucopolysaccharide: MPS1 (iduronidase deficiency)
Urine reducing sugar:
GSD: Accumulation of Glycogen due to G6P deficiency
1.Von Gierke (L,UA,HB)
2.Pompe (Cardiac)
3.Cori (Mild)
4.Andersen (L,child death)
5.McArdle (Muscle)
6.Hers (~Von Gierke)
1,4,6 = Liver
2,5,7 = Muscle
D-xylose absorption test: Differentiate Pancreatic insufficiency from malabsorption
8
Q
When is Iron in Fe2+ (3) / Fe3+ (1) form? In what condition is Iron absorption increased (3) / decreased (1)?
A
Fe2+: absorption, Ferrozine binding, in Hb
Fe3+: transferrin binding, MetHb
Absorption increase in alcoholism, low gastric pH, IDA
Absorption decreased in IDA
9
Q
Can you determine if a patient is having Iron deficiency based on a single measurement? (1) How about Ferritin? (2) Name a test that is helpful for IDA diagnosis in difficult cases. (1)
A
No, because Iron is elevated by hemolysis and is subject to diurnal variation (higher during work)
Low Ferritin is specific but not sensitive for IDA, as Ferritin is elevated in malignancy, infection, and inflammation, masking the Low Ferritin caused by IDA.
sTfR increase suggest IDA, this increase is not affected by inflammation
10
Q
How can you differentiate IDA, Iron overload & ACD using Iron panel? (3) Why Iron panel result in Iron overload is similar to hemolytic & sideroblastic anaemia? (2) How about Nephrosis, Hepatitis & Pregnancy? (3)
A
Fe is high in Iron overload
TIBC is high in IDA but low in ACD
Fe is released in hemolysis, resembling a state of Iron overload
Nephrosis: urinary loss of Fe & Transferrin
Hepatitis: ferritin release & transferrin synthesis decrease
11
Q
Where are Heme, BILI & conjugated BILI produced respectively? (3)
A
Heme: Bone & Liver
BILI: Spleen & Liver
conjugated BILI: Liver
12
Q
What is δ Bilirubin? How would it affect DB results? (2)
A
δ BILI = irreversibly albumin bound BILI
δ is not a Conjugated BILI but is measured as DB
High δ Bilirubin to Conjugated BILI ratio indicate effective of biliary drainage, which rule out cholestasis.
13
Q
Why is Urine Urobilinogen high in AIHA but low in cholestasis? (2)
A
High in extravascular hemolytic anemias (Splenic removal, in AIHA / HS) as more BILI is released to GI & be converted to urobilinogen by enteric bacteria
Low in cholestasis because urobilinogen can’t be produced without BILI being released to GI
14
Q
Bilirubin can be affected by drugs, name 2 of them. (2)
A
Barbiturates lowers BILI, it is used in treatment of jaundice
Chlorpromazine increases BILI, it is an antipsychotic that causes cholestasis
15
Q
DB should be measured faster, TB measurement involves caffeine, why? (3)
A
To prevent unconjugated BILI from reacting during DB measurement, measure within 3 minutes OR reduce diazo group using ascorbate to stop reaction
Accelerator is required for unconjugated BILI to react during TB measurement
16
Q
Why do some labs measure NB with bichromatic spectrophotometric methods? (2) Why Neonate has high BILI? (1)
A
Negative interference persist as Hb itself inhibit diazo reaction
NB are usually Hemolyzed, consider Direct bichromatic spectrophotometric methods (454 nm and 540 nm) for NB to prevent underestimation of BILI
Physiological hyperBILI in neonate is due to hemolysis & relative UGT deficiency, the BILI is mostly unconjugated, persist for 1 weeks for normal / 2 weeks for prematures babies
17
Q
Enzymatic method for BILI measurement uses different pH for DB & TB, explain. (2) Name a bedside method. (1)
A
At pH 8, both conjugated, unconjugated, and delta bilirubin react with the enzyme
At pH 4, only the conjugated form reacts.
At bedside, there is Multiwavelength reflectance photometry for transcutaneous bilirubin assay
18
Q
Why is DB high in hepatitis when liver function is low? (1)
A
Although theoretically liver dysfunction causes conjugation problem leading to increase in unconjugated BILI, DB is also high due to re-excretion failure and cholestasis
19
Q
High BILI may be attributed to diseases related to bile transport & UGT deficiency, name 5 of them. (5)
A
Bile transport: Dubin–Johnson, Rotor
UGT deficiency: Crigler–Najjar, Gilbert’s, Lucey–Driscoll
20
Q
CRE tends to overestimate GFR, especially for men having low GFR, why is that? (1)
A
CRE is 100% filtered by the glomeruli, in addition, secretion especially at low filtration rate. Low GFR means more CRE secretion, so the apparent plasma CRE is lower, overestimating the actual GFR.
21
Q
Why do men & women have different reference ranges for CRE? (1)
A
They has different muscle mass
22
Q
Why is CrCl measurement with plasma & 24h CRE prone to preanalytical error? (4) How about calculated CrCl? (1)
A
CrCl = U/P X V X 1.73/A (A differs so use separate RI for M / F / Child)
Not empty bladder at start (Falsely High)
Adopt MSU procedure (Falsely Low)
Not empty bladder before end (Falsely Low)
<400mL 24H urine due to dehydration (secretion, Falsely High)
Cockcroft-Gault: drug dosing adjustment
calculation depends on age, gender, weight
CrCl, mL/min = (140 – age) × (weight, kg) × (0.85 if female) / (72 × Cr, mg/dL)
23
Q
Name 2 method for eGFR calculation & comment on the major difference. (2) What are the variables in their calculation? (3)
A
MDRD:
underestimate for eGFR>60, invalid for child & elderly & seriously ill
CKD-EPI:
more accurate for eGFR>60, choice for adult CKD monitoring
For MDRD & CKD-EPI, calculation depends on age, gender, race
24
Q
What are the main concerns of Jaffe’s reaction over enzymatic methods in measuring CRE? (2) How can we reduce those concerns? (3) How would it potentially affect our patients if those concerns are not tackled? (1)
A
BILI negative interference, minimized by sample dilution, rate-blanking, or manual deproteinization
ascorbate, ketone & protein positive interference, compensated by subtracting a constant value
Falsely Low CRE can lower MELD score can delay liver transplant for patient in need
25
Why CHO and LDL is high in nephrotic syndrome?
Low ALB upregulates HMG CoA Reductase and downregulate LPL
26
Name 5 causes of low MG. What will happen when a patient has low MG? (4)
Alcoholism, GI tract disease, Diarrhea/Vomiting, parenteral feeding, DKA
Hyperactive including seizures, tremor, tachycardia, swallowing problems
27
Why is plasma urea useful for accessing prerenal cause of decreased renal function? (1)
Urea reabsorption is filtration rate dependent
28
If the patient has renal & liver failure simultaneously, how would plasma urea change? (1)
No change, liver failure reduces urea synthesis, renal failure reduces urea excretion.
29
Can we measure URE without using enzymes? (1)
Yes.
Electrochemical method measures current increases caused by NH4+ production
30
Name 7 conditions related to aminoaciduria? (7)
1.PKU is accumulation of phenylalanine due to phenylalanine hydroxylase deficiency
2.Fanconi syndrome is inherited renal-type due to renal tubule defects
3.Homocystinuria is inherited overflow-type due to cystathionine synthase deficiency
4.Wilson’s disease is inherited overflow-type due to urea cycle failure
5.Hepatitis is acquired overflow-type due to urea cycle failure
6.Alkaptonuria is due to homogentisic acid oxidase deficiency
7.MSUD is due to branched-chain decarboxylase deficiency, leading to Valine, leucine, and isoleucine accumulation
31
Name 4 methods for AA measurement, which is most common? (5)
ESI-MS-MS, HPLC, CE, 2D TLC (SiO2polar, mobile phase basic & acidic)
ESI-MS-MS
32
Why would someone have a high AMM? (2) Why is it not good? (2) Anything to consider before taking blood for AMM? (3)
Hepatic coma (severe liver necrosis)
ammonia increases central nervous system pH and is coupled to glutamate (neurotransmitter)
Venous stasis and prolonged storage cause peripheral deamination of amino acids
Smoking can double AMM, fasting is recommended
33
Apart from Renal, Cancer & Gout, UA is also high in ketoacidosis & lactic acidosis, why is that? (1) Suggest an urgent condition that requires UA measurement (1)
They compete with uric acid for renal excretion.
Uric acid calculi obstructing ureter
34
What is the full name of A & B antigen, and Anti-H? (3)
A = N-acetyl-D-galactosamine
B = D-galactose
Anti-H = ulex europaeus
35
Do ABO causes HDFN? (1) How? (1) Is it serious? (1)
ABO induced HDFN is common but weak (DAT weak+, as fetal RBC has weak ABO expression)
Due to IgG Anti-A,B from O mom.
36
What would you do if reverse A is 1+ and you suspect it is the culprit of ABO discrepancy? (1)
Add Anti-A1 Lectin to determine if the patient is A2 subgroup
37
Order of H abundance (1) What is the use of adding Anti-H to A1 cell? (1)
O> A2 > B > A2B > A1 > A1B
As a negative control when solving ABO discrepancy with Anti-H.
38
Why sometime rouleaux is observed in forward & reverse grouping? (1) what would you do? (1)
High protein in plasma (MM)
Use washed patient's RBC suspension for forward
Add ALB to dilute the mixture for reverse.
39
What would you do if forward groupings are all positive? (1)
Do AC (patient RBC+ patient plasma) to rule out AutoAb
40
Why is plasma urea useful for accessing prerenal cause of decreased renal function? (1)
Urea reabsorption is filtration rate dependent
41
If the patient has renal & liver failure simultaneously, how would plasma urea change? (1)
Urea can be normal. RF reduces urea excretion, LF reduces urea synthesis
42
Can we measure URE without using enzymes? (1)
Yes.
Electrochemical method measures current increases caused by NH4+ production
43
Name 7 conditions related to aminoaciduria? (7)
PKU is accumulation of phenylalanine due to phenylalanine hydroxylase deficiency
Fanconi syndrome is inherited renal-type due to renal tubule defects
Homocystinuria is inherited overflow-type due to cystathionine synthase deficiency
Wilson’s disease is inherited overflow-type due to urea cycle failure
Hepatitis is acquired overflow-type due to urea cycle failure
Alkaptonuria is due to homogentisic acid oxidase deficiency
MSUD is due to branched-chain decarboxylase deficiency, leading to Valine, leucine, and isoleucine accumulation
44
Name 4 methods for AA measurement, which is most common? (5)
ESI-MS-MS, HPLC, CE, 2D TLC (SiO2polar, mobile phase basic & acidic)
ESI-MS-MS
45
Why would someone have a high AMM? (2) Why is it not good? (2) Anything to consider before taking blood for AMM? (3)
Hepatic coma (severe liver necrosis)
ammonia increases central nervous system pH and is coupled to glutamate (neurotransmitter)
Venous stasis and prolonged storage cause peripheral deamination of amino acids
Smoking can double AMM, fasting is recommended
46
Apart from Renal, Cancer & Gout, UA is also high in ketoacidosis & lactic acidosis, why is that? (1) Suggest an urgent condition that requires UA measurement (1)
They compete with UA for renal excretion.
Uric acid calculi obstructing ureter
47
What is the full name of A & B antigen, and Anti-H? (3)
A = N-acetyl-D-galactosamine, B = D-galactose
Anti-H = ulex europaeus
48
Do ABO causes HDFN? (1) How? (1) Is it serious? (1)
Yes.
Anti-A,B from O mom.
ABO induced HDFN is common but weak (DAT weak+, as fetal RBC has weak ABO expression)
49
What would you do if reverse A is 1+ and you suspect it is the culprit of ABO discrepancy? (1)
Anti-A1 Lectin is useful in determine if the patient is A2 subgroup
50
Why sometime rouleaux is observed in forward & reverse grouping? (1) what would you do? (1)
High plasma protein (MM)
Use Washed RBC for forward
Dilute reverse mixture
51
What would you do if forward groupings are all positive? (1)
Do AC (patient RBC+ patient plasma) to rule out AutoAb
52
What would you do if reverse O is positive? (2)
consider Bombay, or cold agglutinin
Anti-H to Patient’s cell to rule out Bambay
Prewarm to warm out cold Ab such that Ab screen & ID reflects AlloAb
53
What are the common Rh phenotypes in the Asian population? (2)
R1, R2
54
Chromosome for ABO & Rh? (2)
ABO: 9
Rh: 1
55
Practically, how to demonstrate weak D? (2) how about partial D? (1) If you have only 1 unit O- blood, who would you give it to? (1)
weak/partial D: weak reaction with Anti-D
partial D = more reactive with another brand of Anti-D
Give it to patient with partial D as their plasma contain Anti-D
56
Pregnant women often tested Anti-D+, why is that?(1)
RhIg is prescribed for O- mom to prevent RhD immunization
57
Describe the function of enzyme-treatment (3) & AET (1)
Enhanced:
ABO (ABO/H,Lewis,I,P1PK)
Rh
Kidd
Decreased:
MNS
Duffy
Unchanged:
Kell
AET treated cells denatures Kell Ag
58
In CMC, what would you do if ColdAutoAb is suspected? (1) is there risk of doing so? (1) how about WarmAutoAb? (1) What would RC do for the specimen you send to them? (1)
ColdAutoAb: Prewarm.
Risk of removing clinically significant Ab with wide thermal amplitudes (anti-Vel)
WarmAutoAb: Ab screen & ID would always be +, proceed to phenotyping & give patient with phenotype-matched IAT-compatible blood after physician consent.
RC would use techniques like Autoadsorption, Alloadsorption (homozygous M cells for ColdAutoAb), and Enzyme-treatment to confirm their presences.
59
Jka is notorious for not being detected & causing DHTR, why is that? (1) Why is DAT positive in HTR? (1)
Antibody produced in primary immune response decreases in titer and become indetectable at Ab screen before 2nd transfusion, so the transfusion proceed and HTR occurs due to secondary immune response.
DAT suggests IgG coated on RBC, which triggers hemolysis.
60
Why is Frequency data useful when you want Antigen-negative blood but don’t want to wait? (1)
Frequency data from Red Cross may be used to calculate the estimated number of random XM required before a match can be found
61
If you issue 1 unit of O+ blood to O- mother, is it absolute that she will develop Anti-D?(1)
There is 22% chance for Rh- patients to develop Anti-D after 1 unit Rh+ RBC transfusion.
62
For panagglutinin with AC+ we would consider warmAutoAb, if it is AC-, what would you suspect? (1)
consider multiple Ab to low frequency Ag if reaction strength differs.
consider Ab to high frequency Ag like Anti-k, k is not phenotyped in routine practice because k- is very rare.
63
Why is phenotyping of SCD patients possible even after transfusion?(1)
Patient with SCD who is transfused recently can still be phenotyped after treatment with hypotonic saline, as transfused RBC are all lyzed by osmosis
64
What are the 3 rules when interpreting ABO discrepancy? (3) Give 5 examples of ABO discrepancy (5)
1. Always correlate Clinical history
2. weak reaction = discrepancy
3. Ab problems are more common than Ag problems
4+ 4+ 2+ 0 = A2B
0 0 0 0 = Immunocompromised
4+ 4+ 2+ 2+ = Cold agglutinin
4+mf 4+mf 0 0 = AB patient received O blood
4+ 2+ 0 4+ = Acquired B due to GI disease, no longer a problem with current Anti-B
65
In a case of Ab- with Anti-Jkb history, you proceed to XM with Jkb- blood, it is 1+, give 2 possible explanations to this. (2)
1. Ab to high frequency Ag (Anti-k) in patient plasma.
2. DAT+ donor cell.
66
In a case of Ab- without history, you issue blood by CXM & the blood is transfused. Next Ab screen shows DAT+(mf) suggesting DHTR, is it your fault? (1)
No, there is systemic risk of DHTR following protocol of giving CXM blood to Ab screen - patient.
Antibody produced in primary immune response decreases in titer and become indetectable at Ab screen before 2nd transfusion, so the transfusion proceed and HTR occurs due to secondary immune response.
67
When panagglutination is encountered, always do AC & DAT, why? (1)
AC+ & DAT+ confirm WarmAutoAb case and rule out Ab to high frequency Ag (Anti-k, although not likely)
68
When you see Ab(?), what would you suspect? (1) What would you do to prove your suspicion? (1) What to do next if your suspicion is likely? (1)
ColdAutoAb
DAT + (C3d+)
Prewarm for Ab screen, ID & XM
69
A patient is DAT+, does it mean he has AIHA? (1)
AutoAb != AIHA, AIHA ~= AutoAb
70
Aetiology of TTP, HUS, DIC. (3) State 1 thing you should do & 1 thing you should never do for TTP patients. (2) How to differentiate TTP & HUS? (2) Why is ITP not related to schistocytes? (1) How to rule out DIC? (1)
TTP : ADAMTS13 deficiency (<10%)
HUS: E. coli O157:H7 OR complement-mediated HUS
DIC: APL / Sepsis / Malignancy
perform plasma exchange & avoid PLT transfusion for TTP suspected cases
TTP: Neurological
HUS: Renal
ITP is caused by viral infection, Ab opsonization of RBC facilitate extravascular removal at spleen.
Absence of D-dimer elevation & PT/APTT prolongation rule out DIC.
71
Patient is having panagglutination with AC+ DAT+, XM incompatible for units tested, what should you suggest when immediate blood transfusion is indicated? (1), when blood transfusion is indicated later? (1)
unmatched O / group-specific blood.
When phenotype is available, phenotype-matched incompatible IAT can be issued with physician consent.
72
Patients having ITP received PLT but PLT count remains low, what would you recommend the physician to prescribe that can potentially improve the condition? (1)
Try IVIG(Anti-D), macrophage engulf excess IVIG, sparing opsonized PLT.
Steroid + IVIG(Anti-D), TPO R agonist, Fostamatinib (Sky inhibitor, inhibit Anti-PLT production & Macrophage opsonization), splenectomy, immunosuppression
73
O- women called MTP, BB only have 4 units of O- blood, what would you do? (2)
If MTP is really massive, skip O- blood, give O+ blood instead. women is going to be sensitized anyway due to the shortage of O-, so we better reserve O- for other patients.
If MTP is not massive, give the O- blood, consider give A2- as well if it is available (A2 cell contain least A Ag), then transit to O+ blood.
74
A- man with Anti-D called MTP, BB only has Rh+ blood, what would you do? (2)
Give Rh+ blood, monitor hemolysis, transit to Rh- post-operative.
75
Elution helps in TR investigation, DTT helps in patients receiving daratumumab, prewarming & cord blood helps in Cold Ab investigation, homozygous cell helps in Ab ID of Ag having dosage effect. Describe how. (4)
Elution: detach IgG from RBC, then perform Ab ID on eluate
DTT: remove CD38 & Kell Ag from RBC, facilitate detection of AlloAb after daratumumab[Anti-CD38] treatment
cord cell: i Ag predominant, used to confirm Anti-I
homozygous cell: homozygous cell usually has two alleles for the Ag (not always), so its reaction with Ab is stronger.
76
Name 6 antihyperlipidemic medications & explain how they work. (5)
What are their side effects? (5)
1. Ezetimide (inhibit CHO absorption)
-diarrhea
2. Statin (inhibit HMA-CoA R)
-liver toxicity, rhabdomyolysis
3. Fibrate (stimulate LPL)
-liver toxicity, Gall stone
4. bile acid sequestrant [Cholestyramine] (inhibit bile acid reabsorption)
-Fat malabsorption, Gall stone
5. Niacin (inhibit lipolysis, inhibit VLDL secretion)
-Flushing (Give aspirin), High UA (renal excretion competition), High GLU (insulin resistence)
6. PCSK9 I (Antibodies, PCSK9 cleaves LDL R on hepatocytes)
77
How hemolyzed sample affects the result? (1)
High H index:
1. Color interference (colorimetric assay with similar wavelength)
2. Release of RBC content (LDH, PHOS, K, AST, FOL, ALT, MG, FE)
3. Sample dilution [>3g HB] (ALB, BILI, GLU, NA)
4. Chemical interference (competition, inhibition, ppt., Protease[Cathepsin E: Low Insulin, BNP])
78
Name 6 acute TR & 4 delayed TR. (10)
Acute TR:
1. Allergic (sensitive to donor plasma protein)
2. FNHTR (HLA, cytokine)
3. Septic (donor unit with bacteria)
4. TACO (Excess volume of transfusion)
5. HTR (Incompatible)
6. TRALI (Anti-HLA from donor attacks patient's lung)
Delayed:
1. DHTR (2nd immune response, Jka,CcEe)
2. GVHD (proliferation of donor Lymphocyte in patient's BM)
3. Viral (window period, product recall)
4. FE overload (repeated transfusion [aplastic anaemia, THAL major])
79
Indications of giving RBC, PLT, Plasma, CRYO & Leukocytes. (5)
RBC:
1. HB<7
2. HB>10 who can't tolerate anaemia
PLT:
1. PLT<10
2. PLT<20 with sepsis
3. PLT<50 with mucosal bleeding
4. PLT<100 with CNS bleeding
5. PLT<50 for premature neonates (PLT<100 for sick)
6. Suspected PLT dysfunction / deficiency after MTP
#Avoid giving PLT in MAHA cases
Plasma:
1. TTP
2. Warfarin reversal (consider PCC if available)
3. PT/APTT>1.5X + HaemophiliaA/B OR DIC OR hepatic failure
4. Suspected Factor deficiency after MTP
CRYO (1,8, vWF,13):
1. vWF (consider DDAVP if available, beware of Low NA)
2. FIB deficiency
3. Factor 13 deficiency
Leukocytes:
1. N<0.5 with no response to antibiotic >2d
80
Indication of irradiated, CMV-, Rh- RBC. (3)
Irradiated for BMT (Lymphocyte division is inhibited to prevent GVHD)
CMV- for CMV- pregnant / BMT patient, and patient with HIV
Rh-
1. HDFN Anti-D+
2. Rh- Anti-D+
3. Rh- women
4. Rh? white women
5. Rh-
81
What is epilepsy? (1)
Name anti-epilepsy drugs & their mechanism of action. (8)
Why taking anti-epilepsy drugs with oral contraceptive is a bad idea? (1)
Give two consideration for when prescribing anti-epilepsy drugs to pregnant women. (2)
chronic seizures (synchronous depolarization)
+involuntary muscular movement = convulsion
For neuron, + entry = depolarization (activation), CA enter causes release of neurotransmitter
ALB is carrier of most drugs, so Low ALB (L/R disease) increase drug toxicity
anti-epilepsy:
Carbamazepine: Na
Phenytoin & Valproic acid: Na & CA
Ethosuximide: CA
Barbiturate: CL[GABA] (duration)
Benzodiazepine: CL[GABA] (frequency)
ViGABAtrin: GABA transaminase inhibition
Topiramate: AMPA(NA) Glutamate R inhibition
Felbamate: NMDA(CA) Glutamate R inhibition
anti-epilepsy drugs (except Valproic acid) upregulate P450, increasing rate of OCP metabolism
Anti-epilepsy drugs are teratogen & interfering folate absorption. Order AFP (neural tube defect) & give folate.
82
What are pre-eclampsia & eclampsia? (2) Name 4 organs affected. (4)
How to prevent eclampsia? (1)
pre-eclampsia: narrowing of Uteroplacental artery induces pro-inflammatory protein release causing vasoconstriction.
Kidney: High UTP
Eye: Scotoma
Liver: HELLP (Hemolysis, Elevated Liver enzyme, low PLT)
Brain: cerebral edema causing seizures (eclampsia)
Give MgSO4 to patient with pre-eclampsia
83
We use BCG for ALB measurement. Is BCG specific for ALB? How about BCP? (2) Name 1 interference for BCG & BCP respectively (2)
No. BCG react faster with ALB but also react with Globulin.
BCP has higher specificity for ALB.
BCG: Penicillin
BCP: Organic acid in renal dialysis patients
84
Kjeldahl Method measures Nitrogen content & converts it to TP. Why do we use Biuret instead of Kjeldahl for routine TP measurement? (1) tartrate & KI exist in Biuret reagents, why? (2)
Kjeldahl requires tedious titration & boiling steps.
Tartrate salt prevents turbidity
KI prevents Cu autoreduction (favorable in alkaline)
85
I want to measure UTP without using turbidity by Benzethonium chloride, how? (1)
Folin–Lowry modification of Biuret method may be used, it has increased sensitivity.
86
Why do ward patients have lower TP, ALB, HCT & CA? (1)
They are laying down instead of sitting/standing.
Standing patient has 10% higher TP, ALB(CA), CHO, WBC, RBC due to shifting of water out of blood vessel.
87
Plasma protein is higher than serum protein, why? (1)
FIB is used during clot formation, forming serum.
88
Name 1 condition that causes High ALB & Low ALB respectively (2)
High ALB: dehydration
Low ALB: Inflammation, after ruling out cirrhosis, loss (burn, hemorrhage)
89
State SPE fractions from fastest to slowest. (5) which fraction is related to the Iron panel, hemolysis & cystic fibrosis respectively? (3)
ALB, alpha1, alpha2, beta, gamma
Iron panel: beta (transferin)
hemolysis: alpha2 (haptoglobin)
cystic fibrosis: alpha1 (alpha1 antitrypsin)
90
Point the finding in SPE for Cirrhosis, Wilson’s, Malignancy/RA, MM, Inflammation, & CF (5)
Cirrhosis: β-γ bridging (IgA)
Wilson’s: Low α2 (ceruloplasmin)
Malignancy/RA: Polyclonal γ + inflammation
MM: Monoclonal γ (sometimes β / α2)
Inflammation: α1 (α1-antitrypsin), α2 (haptoglobin)
CF: α1 Low, α2 (chronic emphysema[Inflammation]), γ (Cirrhosis)
#ALB Low whenever inflammation is involved
91
Why low buffer ionic strength increases analyte mobility?(1)
When ionic strength decreases, current decreases, but the current force is used to move analyte, increasing analyte mobility.
92
Why are Serum SPE & Urine bence jones protein both required for MM screening? (1) Why is the Serum light chain used in MM monitoring? (1)
24h Urine bence jones protein is necessary to rule out MM because 25% MM patient has heavy chain gene deletion and the remaining monoclonal light chain is filtered & can be detected only in urine. polyclonal gammopathies can cause false positive
Serum-free light chain immunoassay is sensitive in detecting early monoclonal gammopathies, good for monitoring also due to shorter plasma half life than intact Ig
93
Why do CSF SPE? (1) How to treat the CSF sample before SPE? (1) How can you confirm the bands in CSF SPE only exist in CSF?(1)
For MS, IgG index is sensitive but not specific. gamma oligoclonal banding in SPE in 90% MS patient .
CSF sample should be Concentrate 100 times to increase sensitivity.
gamma oligoclonal banding observed in CSF SPE should be absent in serum SPE.
94
What is the K/L ratio & why is it important in MM diagnosis? (2)
Normal K : L ratio ~= 2:1. Alteration implies monoclonal Antibody.
95
How does SDS-PAGE differ from agarose gel? (1) Apply them to Lipoprotein separation. (1)
SDS-PAGE: based on size
– Chylomicrons→pre-β(VLDL) →β(LDL)→α(HDL) +
agarose gel: based on size & charge
– Chylomicrons →β(LDL)→pre-β(VLDL)→α(HDL) +
96
Haptoglobin is not useful in diagnosing hemolysis in a state of inflammation, suggest another test in this case. (1)
Haptoglobin binds free Hb after hemolysis, but its synthesis increase in inflammation as an APR, masking the drop in Hp, consider Hemopexin to confirm hemolysis in this case
97
In PMH, Hb pattern is performed using HPLC, describe the procedure. (6)
PMH uses bio rad variant ii for Hb pattern
1. Select sample (MCV&MCH Low, No history, No Transfusion)
2. Check RT & Area for Cal, F & A2 results for QC
3. Early elution peak existence = HbH likely = re-H if -
4. HbH>3%/Early peak/Hb variants = Alk Gel
5. HbSCED for confirm = Acid Gel
6. unresolved cases / OBS&IVF cases = CE (Sebia)
98
Describe the 4 types of inherited hyperlipoproteinemia & the 3 types of acquired hyperlipoproteinemia (7)
Inherited
1. LPL deficiency
2. apo-B100 mutation (Young patient with MI)
3. apoE mutation
4. excess VLDL release
#Xanthomas, acute pancreatitis
Acquired
1. Cholestasis (accumulation)
2. Nephrotic syndrome (Liver compensate for lost of ALB)
3. DM (insulin induces LPL, lack of insulin causes VLDL accumulation)
99
Describe the Apo affected in Abetalipoproteinemia & Tangier disease respectively (2)
Abetalipoproteinemia: Apo B48 / Apo B100
-fat-soluble vitamin deficiency (A: retinitis, D: osteomalacia, E: acanthocytosis)
Tangier disease: Apo A1, Low HDL
100
Name 7 lysozymal storage disease (7)
1. Fabry
galactosidase, ceramide
My fabrite activity is ceramics. We made a galaXy
2. Gaucher
glucocerebrosidase, glucocerebroside
oh my Gauch, he's such a Bro (tissue paper cytoplasm)
3. Tay-Sachs
hexoaminidase, ganglioside
A Gang of 6 small Jews (no splenomegaly)
4. Niemann Pick
sphinogomyelinase, sphinogomyelin
pick your big nose with your sphinger
5. Krabbe's
galactocerebrosidase, galactocerebroside
the Krabbe is out of this world (globoid cell)
6. Hunter's
iduronate sulfatase, dermatan sulfate
X-marks the spot (no corneal clouding)
7. Hurler's
L-iduronidase, dermatan sulfate
Cherry-red macula: Tay-Sachs & Niemann Pick
101
What are the 4 classes of antiarrhythmic? (4)
Are there other drugs? (3)
1. NA (CAB) [0]
-A = SLE, B = Post-MI
2. NA/K (ol) [4]
-hypoglycemic masking
3. K (AIDS) [3]
-TFT,PFT,LFT
-phlebitis
4. CA [0,3,4]
-Edema
Other drugs:
1. Digoxin
-inhibit NA/K >> 2nd NA/CA >> High CA = High contractility >> CHF
-vagus nerve >> SA >> AF
2. Adenosine
-Acute IV for SVT
3. MgSO4
-de pointes & Digoxin induced arrhythmia
102
What is the upper limit of TG for the Friedewald equation? (1) Suggest another formula with a higher upper limit. (1)
4.52, that's why LDL measurement is required for sample with TG>5.2.
Sampson-NIH2 equation (TG<=9 mmol/L)
103
LDL by either calculation or measurement are not appropriate for non-fasting samples, why? (2)
In non-fasting, chylomicron present, so not all TG are on VLDL, so never use non-fasting sample to determine LDL by calculation (LDL itself increase after meal, so it is not acute even by measurement)
104
What is 1U of enzyme activity? (1)
1IU = quantity of enzyme that Converts 1 μmol of substrate to product per minute
105
State enzymes that requires Mg2+, Ca2+, and vitamin B6 as cofactor respectively (3)
Mg2+: CK ALP
Ca2+: AMY
B6: AST, ALT
106
Why is ALP & GGT increase in cholestasis when no actual cell damage is done? (1)
In cholestasis, ALP & GGT release is based on secretion rather than necrosis
107
CK & AMY results often become higher after dilution / decrease mode, why is that? (1)
Higher than expected result after dilution is common due to endogenous inhibitors of CK & AMY
108
State where LDH1~5 exists in the body. (5) How would LDH level be affected for freezed sample? (1)
1: Heart
2: RBC
3: Brain, pancreas, lung, spleen, kidney
4: kidney, pancreas, placenta
5: Liver, muscle
Freezing cause deterioration of LD-5
109
What is the URL of hsTnI based on? (1) How can physicians rule out MI using hsTnI? (1)
99% percentile of population with CV<10%
0min: Myoglobin / HsTnI
3h & 6h & 12h: HsTnI / CK-MB
110
What is the use of measuring NT-proBNP? (1) Why don’t we measure BNP instead? (1)
1. CHF >> increased intracardiac blood volume >> BNP released by ventricles
2. preproBNP >> proBNP >> BNP & NT-proBNP (inactive)
3. High BNP + ischemia >> Higher risk of MI
4. NT-proBNP value not affected by nesiritide (BNP for treating CHF)
111
State the order of cardiac markers increases after MI. (1) Why is hsTnI still the best even if it is not the first to rise? (1)
Myoglobin, WBC, hsTnI, CK, AST, LDH. 見張っとく気ある？
hsTnI persist 7 days, with high clinical specificity
112
Interpret High results with AST>ALT vs ALT>AST. (2)
AST>ALT:
1. Alcoholism (mitochondrial AST)
2. acute hepatitis (half life of AST)
113
2-amino-2-methyl-1-propanol exists in ALP reagents, why? (1)
Pi product inhibition on ALP activity
Add 2-amino-2-methyl-1-propanol to bind Pi
114
State the 3 ALP isoenzymes & suggest a way to separate them (4)
Heat labile to stable:
Placental / lung cancer ALP > liver ALP > bone ALP
Placental / lung cancer ALP retain activity after 65° C for 10 minutes
If activity <20% after 56°C for 10 minutes, consider bone ALP
115
Suggest 3 conditions that can be diagnosed by ACP (3)
prostatic ACP: seminal fluid, sexual assault
TRAP: hairy cell leukaemia (AP in Lymphocyte), bone cancer (AP in osteoclast)
116
Is AMY specific for pancreatitis? (2) Why measure UAMY & Lipase on top of AMY? (2)
No. It also rise in peptic ulcer, and there is S-type AMY rise in Mumps / ectopic pregnancy.
In acute pancreatitis, AMY rise at 2h & peaks at 12h (5X), return to normal after 4 days, UAMY rise higher & persist 1 week
Lipase rise higher than amylase (~50X)
117
How about chronic pancreatitis? (4)
AMY & Lipase synthesis is compromised in chronic pancreatitis.
Sensitivity of AMY & Lipase in detecting chronic pancreatitis is <50%, consider faecal fat increase & trypsin / chymotrypsin / elastin decrease
118
Explain why Le(a-b+) patient won’t develop Anti-Lea (1)
Lea still exist in patient plasma, just the quantity is insufficient to adsorb to RBC & be detected as phenotype.
In Se(w) patient, less Ag is converted to H so less is further converted to Leb, and more Ag is available to be converted to Lea, therefore patient phenotype can be Le(a+b+).
119
Describe 3+3 rule in Antigram interpretation (1) How WarmAutoAb & Dosage effect influence Antigram interpretation? (2)
3+3 rule for Ab ID is based on 1/20 probability by chance as calculated using Fisher's exact method, meaning 95% confidence in correct Ab ID, other combination is ok as long as the p is <= 1/20
heterozygous panel cell, along with weak Ab, Anti-C', and Ag not in panel cell, are the reasons of -ve AbID.
WarmAutoAb causes panagglutination (ALL +ve AbID), with DAT+.
If DAT-, possibility of Multiple AlloAb, Anti-H, Anti-high frequency Ag should be considered.
120
Suggest a possible culprit of warm AIHA & cold AIHA respectively (2)
-warm AIHA can be Anti-e, although in most cases its specificity can’t be determined. Finding e- blood is difficult e is has frequency in population. SLE is a cause of warm AIHA.
-cold AIHA can be Anti-I / i, which can be confirmed with negative reaction with cord blood as it contains only i antigen, Anti-i ~= mononucleosis (EBV)
121
Weak Panagglutination with AC-, what would you suspect? (1) How to prove? (1)
Anti-high frequency Ag with HTLA characteristic.
For HTLA, serial dilution of plasma would affect the strength of its reaction, but all reactions are weak.
122
Anti-Lua vs Anti-Lub, which is more common? (1)
-Anti-Lua usually exist as Lua is low frequency antigen, Lub is high frequency antigen & Anti-Lub is rare & may cause hemolysis.
123
Why don’t we use EDTA samples for the Cold agglutinin test? (1)
-For Cold agglutinin test, store at 4C<48h is recommended for C’ activity. Plasma sample is inappropriate as anticoagulant chelate Ca required for C’ actions.
124
State Ab involved for PCH, CAD, IM(EBV), M. pneumoniae. (3) How about PNH? (1)
PCH: IgG (IgM / A) Anti-I / P, also called Donath–Landsteiner antibody
-biphasic: Attach RBC at 4C, Hemolysis at 37C
CAD: IgM Anti-I
IM(EBV): IgM Anti-i, mostly child
M. Pneumoniae: Anti-I, mostly adult
#titer >64 = +
PNH: Not Ab induced. It is PIGA mutation causing CD55/59 deficiency, which weaken C’ inhibition, this apply to WBC & PLT as well (Pancytopenia)
125
Why did we Irradiate RBC? (1)
Lymphocyte division is inhibited to prevent GVHD
126
State the WBC standard of Leukocyte-reduced RBC, the PLT standard of apheresis PLT (2)
WBC < 5 * 10^6
>3.0 × 10^11 PLT (10^9 for PLT count)
127
Which blood product is indicated for patients with IgA deficiency? (1)
Patient with IgA deficiency may develop Anti-IgA, which is an allergic transfusion reaction, consider giving washed RBC
128
Can I transfuse O+ plasma to O- women? (1)
Yes.
Rh is irrelevant in plasma transfusion
129
O- mom with Anti-D -, rosette test -, dose of RhIg? (1)
-rosette test (FMH,+Anti-D to maternal blood, add indicator cell to form a rosette) >> kleihauer test (HbF in maternal circulation, based on HbF resistance to acid)
rosette test negative = no fetal blood in maternal circulation = give 1 dose RhIg
130
O- mom with Anti-D -, rosette test +, kleihauer (25 fetal cell / 4000 maternal cell), dose of RhIg? (1)
-kleihauer test calculation:
x fetal cell / 2000 maternal cell counted * 5000 / 30
n (0.1~0.4): +1; n (0.5~0.9): +2
#5000mL is maternal BV, 30mL is protection volume by 1 vial RhIg
#Calculate maternal BV based on weight using 70mL/kg
=1.04 (+1) = 2
131
Suggest 3 actions that can be taken when maternal Anti-K is detected for Foetus with K antigen. (3)
1. Early labour
2. Plasmapheresis
2. Intrauterine transfusion (>20weeks with fetal hemolysis observed)
132
Why should a Kleihauer test be performed to prove Maternal weak D? (1)
The weak D can be caused by fetal RBC & not reflecting maternal phenotype
133
Normal CSF GLU & Protein compared to plasma. (2) When you see GLU low & Protein high, what would you consider? (4)
CSF Glu = 60% Plasma Glu
CSF Protein is trivial compared to Plasma Protein, *2 for neonate
Low GLU High TP:
SAH, MS, malignancy, bacterial (High Lactate) / fungal meningitis
134
Name 2 tests of CSF requiring urgent sendout to MICRO. (2) Why is it urgent & how are they performed? (3)
Cell count & Gram stain.
Detect Pleocytosis & DC to determine infection type
-always perform DC for newborn & patient with WBC> 5/μL
-Cytocentrifugation to concentrate the sample before Wright’s stain
N = bacterial, L = viral, both = TB/fungal
MS & leukaemia
-Pleocytosis in traumatic tap should have WBC count corrected by RBC count in CSF
-Corrected WBC count = WBCs in CSF – [(Blood WBCs × CSF RBCs) ÷ Blood RBCs]
Neonate
Group B Streptococcus
E. coli
Children
Haemophilus influenzae
S. pneumoniae
N. meningitidis
Elderly
S. pneumoniae
135
Name two ways to differentiate Traumatic tap vs SAH (2)
visual Xanthochromia for SAH
Low opening pressure during CSF collection implies decreased CSF volume (Traumatic tap)
136
Describe two tests for MS, which is more specific? (3)
-For MS, IgG index is sensitive but not specific, gamma oligoclonal banding in SPE in 90% MS patient (those band should be absent in serum SPE)
-IgG index = (CSF/Plasma IgG) / (CSF/Plasma ALB) ; >0.85 = MS / infection
137
Can you send aliquot for CSF CHEM to MICRO? (1)
No.
1st aliquot CSF send to CHEM as contamination is likely, 2nd aliquot sent to MICRO
138
After a car accident, there is colourless discharge from the patient's nose, how to tell if it is CSF? (1)
β-2 transferrin (tau protein) in CSF only
139
What are the 4 steps of hemostasis? (4)
PLT plug formation steps. (3)
Based on the mechanism, suggest why aspirin, clopidogrel, Abciximab, & dipyridamole are antithrombotic. (4)
Also, correlate BSS, vWD, TTP, GT, ITP to the story.
1. v.c.
2. PLT aggregation
3. Coagulation (Fibrin formed trap RBC)
4. Fibrinolysis
PLT plug formation
1. Adhesion (S.E.C exposed, GP1b~vWF)
2. Activation (PLT granule release, Ca dependent)
-ADP >> P2Y12 R - ADP >> activate GP2b/3a
-TXA2 >> PLT aggregation & v.c. (Gi: cAMP Low: CA High)
3. Aggregation (GP2b/3a-Fibrinogen)
aspirin is COX I, causing TXA2 inhibition.
clopidogrel is P2Y12 RI, blocking ADP action.
Abciximab is Anti-Gp2b/3a.
dipyridamole is PDE I, preventing cAMP degradation.
GP1b defective in BSS. vWF defective/deficient in vWD. vWF excess in TTP due to ADAMTS13 deficiency.
GP2b/3a defective in GT, it is also the target in ITP.
140
What are the inducers & inhibitors of P450? (11)
CRAP GPS induces my rage
C: Carbamazepine (anti-epilepsy)
R: Rifampin (antibiotic)
A: Alcohol
P: Phenytoin (anti-epilepsy)
G: Griseofulvin (anti-fungal)
P: Phenobarbital (anti-epilepsy)
S: Sulfonylurea (insulin inducer)
inhibitor:
Valproic acid (anti-epilepsy)
Isoniazid (anti-TB)
Amiodarone (class 3 antiarrhythmic)
Grapefruit juice
P450 is for metabolism of drugs, so P450 inducer causes low drug level, and P450 inhibitor causes high drug level.
141
Give 5 P450 subtypes & the drug they metabolize respectively. (5)
CYP1A2: ACET (2A)
CYP2E1: Ethanol (21y for alcohol)
CYP2C9: Warfarin (2,7,9,10,C,S)
CYP2D6: cardiovascular drug (2D echo)
CYP3A4: Others
142
When you suspect patient has alcohol intoxication, both Osmolal gap & Anion gap should be calculated, why? (2)
Name 1 drug for treating alcohol intoxication. (1) What if the hospital don't have this drug? (1)
Alcohol DH is an enzyme that convert Alcohol to metabolites.
Ethanol >> Acetic acid >> CO2
Ethylene glycol (anti-freeze) >> Glyoxylic acid
Methanol (moonshine) >> Formic acid
Isopropyl alcohol (hand sanitizer) >> Acetone
Alcohol = OSM gap, Metabolites = Anion gap.
Therefore, OSM gap decreases & Anion gap increases after ingestion.
Except Isopropyl alcohol as Acetone is ketone, not acid
Fomepizole prevents Alcohol DH action so no toxic metabolites are formed.
Give Ethanol (vodka), as Alcohol DH preferentially metabolize Ethanol, which forms non-toxic CO2.
143
Sulfonylurea & Metformin are both DM drugs, what is the main difference between them. (2)
What is the order of drugs prescribed for patient with different level of DM? (3)
Sulfonylurea: Insulin release
Metformin: Insulin sensitivity, causes LA when RF compromised by contrast.
For DM1, give insulin.
Rapid: LAG
Short: Regular
intermediate: NPH
Long: GD
For DM2:
IFG (Diet) >> DM (Metformin + 1 + 2) >> Insulin
1. Sulfonylurea / Meglitinide (-ide)
2. DPP4 I (High GLP1, High Insulin) (-liptin)
3. GLP1 agonist (-tide)
4. SGLT2 I (-flozin) (UTI)
5. alpha-glucosidase I (Acarbose) (GI upset)
6. Thiazolidinedione (TZD) (-glitazone) (bind PPAR-gamma)
7. Amylin analog (help Insulin)
144
Name 2 foods & 1 condition that causes gout. (2)
Treatment of acute & chronic gout is different, explain. (5)
# Treating the inflamed joint, not lowering UA
Red meat & Alcohol >> purine >> UA
TLS: chemotherapy lysis cancer cell, releasing DNA >> purine >> UA
Acute gout:
NSAIDs
Cochicine
#Treating Inflammation, no effect on UA
Chronic gout:
Eat less red meat & Alcohol
Allopurinol (XO I)
Rasburicase (break down UA)
145
Name 1 condition for falsely high & low HbA1C respectively (2)
What test would you recommend to resolve this? (1)
Falsely high: IDA (RBC life span increase)
Falsely low: Dialysis (Blood loss, RBC life span decrease)
GA >20% = DM
146
Explain how IgG, C3C4, and ANA are used to screen for Autoimmune diseases (SLE, RA, SS, SSc).
Suggest follow up tests for SLE, RA, SS, SSc.
IgG high in SS & SLE, although infection, MM & hepatitis should be ruled out first. IgG low after taking steroid.
C3C4 low in SLE (consumption), although cirrhosis should be ruled out first. C3C4 high in inflammation.
ANA high in 100% SLE cases, and 50% RA & MS & SSc cases.
SLE: Anti-dsDNA, Anti-Sm (Any 1 + rash)
RA: Anti-CCP, RF
SS: Anti-SSa/b
SSc: Anti-centromere, Anti-Scl-70
147
What are P-ANCA & C-ANCA test for? (2)
How about Anti-mitochondria, Anti-IF, Anti-smooth muscle, and Anti-GAD.
Different types of vasculitis.
P-ANCA is Anti-PR3
C-ANCA is Anti-MPO
They are inside neutrophil granule until priming by IL-1 & TNF-alpha, when it travels to cell surface & react with their respective Autoimmune Ab, causing neutrophil degranulation & subsequent ROS induced vasculitis.
Specifically, C-ANCA is for granulomatosis with polyangiitis, & P-ANCA for other types of vasculitis.
PBC, pernicious anaemia, AIH, Type1 DM.
148
Name the 4 types of shock.
What is unique about neurogenic shock? (1)
What are the 4 main intervention for patient with shock? (4)
Hypovolemic (Blood loss, Diarrhea, Vomiting)
Cardiogenic (CHF, MI, arrhythmia)
Obstructive (pneumothorax, PM, tamponade)
Distributive (sepsis, anaphylaxis, neurogenic[PNS predominant])
neurogenic: bradycardia (PNS)
1. IV saline (volume increase, BP increase)
2. NE (v.c., BP increase), Digoxin (Cardiogenic shock), E (anaphylactic shock)
149
Name 4 main difference between folate & b12 deficiency. (4)
Why pregnant women should take folate? (1)
Name a drug that causes hypersegmented neutrophil. (1)
Briefly describe B12 absorption. (3)
B12 deficiency
1. Neurological symptoms (demyelination by MMA)
2. MMA accumulation in addition to Homocysteine
-Homocysteine is in methionine cycle, which links to folate cycle
3. Gastric involvement (Anti-IF)
4. liver B12 storage is 3 years so folate deficiency is more likely
Prevent neural tube defect due to folate deficiency.
methotrexate, a folate antagonist for treating cancer & RA.
Pepsin in stomach releases B12 from B12-Protein.
Parietal cell produces IF, which binds B12 at duodenum.
B12 is absorbed at ileum, B12-Transcobalamin at blood vessel.
150
# What are the 11 concepts for verification / validation? (11)
Validation / Verification ? (11)
# Verification = 20, Validation = 60
1. Precision (0.25 / 0.33 TEA)
2. Accuracy (Method mean)
3. Comparison (regression)
4. Linearity (1 & 5 >> 2,3,4)
5. Specificity (interference study, <10%)
6. Sensitivity (LoB, LoD, LoQ [CV<10%])
7. Carryover study (Sequence, sample vs reagent)
8. Hooks effect (Record high)
9. Automated dilution (Undiluted / Manual dilution value)
10. RI validation (20 <2 out range = ok)
11. Internal audit (for extension of service)
151
Normal TG, CHO, HDL, LDL? (4)
TG: <1.7
CHO: <5.2
HDL: >1 / >1.3 (Women)
LDL: <2.6
152
Clinically, how can you tell if patient's CA is low? (2)
trousseau’s and chvostek’s sign
153
Patient has K 7.6, how would you treat him? (2)
1. Give CA gluconate to stabilize the heart (High CA = Less depolarization)
2. Give Insulin with Dextrose (K shift into cell, Dextrose to prevent hypoglycemia)
3. Diuretic (K-wasting), beta-agonist, kayexalate
4. Dialysis (ESRF)
154
Tell the difference between DI & SIADH. (1)
What causes the 2 conditions respectively? (2)
DI: Insufficient ADH
-Urine OSM<200 ; Plasma OSM>300
SIADH: too much ADH
-Plasma OSM<270
DI: neurogenic[vasopressin test] vs nephrogenic
SIADH: neurogenic[tumor,meningitis], SCLC & pancreatic cancer, pneumonia
155
Name 3 difference between MHC1 & MHC2. (3)
1. MHC1 on all nucleated cell & PLT ; MHC2 on APC
2. MHC1 = HLA-A/B/C ; MHC2 = HLA-DP/DQ/DR
3. MHC1-Tumor/Viral Ag-CD8 T ; MHC2-Bacterial Ag-CD4
#beta2-macroglobulin is part of MHC1
156
For DXI we use luminor-ALP, which is an CLEIA. Name 7 methods for Immunoassay. (7)
EIA: ALP, POD
CLIA: acridinium ester
CLEIA: luminor, adamantane
BLEIA: luciferase
RIA: 125I
ECLIA: Ru
FIA: FITC
157
Name Clinically significant cold Ab. (4)
For tube method, we use PEG / LISS to accelerate the agglutination, what is the difference between PEG & LISS? (1)
1. Anti-M
2. Anti-Lea
3. Anti-P
4, Anti-PP1pk
PEG is more sensitive than LISS, with higher false positive rate.
158
ABO anomaly , explain for each case. (4)
Ag gain: DAT+
Ab gain: MM (Rouleaux), ColdAutoAb, AlloAb
Ag loss: Malignancy, Subtype
Ab loss: Immunodeficiency, Old/Young, agammaglobulinemia
159
In lipid transport, state the role of ApoB48, ApoC2, ApoE, ApoB100, and ApoA1. (5)
Why HDL is good cholesterol? (2)
B48: secretion of chylomicron from GI to lymph
C2: Cleaves TG (Activates LPL, just like insulin)
E: Reuptake of renmants by hepatocyte
B100: LDL uptake by peripheral cells
A1: Activate LCAT, convert HDL to mature HDL
HDL donate ApoC2 & ApoE to chylomicrons & VLDL
HDL take cholesterol from peripheral back to liver.
160
State the 5 types of dyslipidemia (6)
What is Abetalipoproteinemia? (2)
1 LP, 2 LD, b adds v, 3 is E, 4 gets more.
1: LPL deficiency, High TG, pancreatitis
2: LDL R deficiency, High LDL, Tendon Xanthoma
2b: +High VLDL
3: ApoE deficiency, High Chylomicron & VLDL, Palmar Xanthoma
4: VLDL overproduction, High TG, pancreatitis
5: 1+4
Abetalipoproteinemia: B48 & B100 deficiency, Steatorrhea, vitamin A (retinitis), vitamin E (SCD)
161
Acetyl-CoA is converted to Palmitate in FA synthesis, but acetyl-CoA is in mitochondria but FA synthesis occurs in cytoplasm, how is this possible? (1)
Which enzyme is rate limiting? (1)
Acetyl-CoA is carried in form of citrate (Citrate shuttle) from mitochondria to cytoplasm to feed FA synthesis.
Acetyl-CoA carboxylase
162
Briefly explain beta-oxidation. (4)
What is common for systemic primary carnitine deficiency, Myopathic CAT2 deficiency, and Fatty Acyl-CoA DH deficiency. (3)
Which enzyme is rate limiting? (1)
1. Carnitine transport is required to move long chain FA from cytoplasm into mitochondria
2. CAT1 & CAT2 is for attaching & removing carnitine from Fatty acyl-CoA respectively.
3. Malonyl-CoA (FA synthesis substrate) inhibit CAT1
All causes low ketone & glucose as beta-oxidation is shunted.
CAT1
163
Briefly explain ketone synthesis. (4)
Name 3 conditions which leads to ketone synthesis. (3)
1. Acetyl-CoA is product of beta-oxidation, which enters either TCA / beta-oxidation
2. Acetyl-CoA *2 = Acetoacetate
3. HMG-CoA Synthase (rate-limiting) >> HMG-CoA
4. Acetoacetate >> Acetone / BHB
End result of all conditions is compromised TCA cycle
DKA: OA depletion due to excess gluconeogenesis (relative glucagon excess)
Starvation: OA depletion due to excess gluconeogenesis
Alcoholism: NAD depletion due to Ethanol metabolism
164
What is glycolysis? (1)
Name 4 related enzyme. (4)
Glycolysis is the conversion of Glucose to pyruvate.
Glucose to G6P by GK (liver) / HK
F6P to F1,6BP by PFK1 [ATP & Citrate+]
F6P to F2,6BP by PFK2 [Insulin+] >> PFK1
PEP to pyruvate [ATP & Citrate+]
165
State 5 destiny of Pyruvate. (5)
Why pyruvate is converted to Alanine? (1)
Cytoplasm
1. Gluconeogenesis to Glucose
2. LDH to Lactate
3. ALT to Alanine [Cahill cycle]
Mitochondria
4. PC to OA
5. PDH to Acetyl-CoA
Cahill cycle
In muscle, pyruvate is converted to Alanine so it can be transported to liver
166
Why HMP shunt exist? (1)
Where it happens? (3)
Name 1 condition related to HMP shunt. (4)
G6P [G6PD] 6PG
For production of NADPH to reduce glutathione, which reduces free radicals.
Cytoplasm of Hepatic, Mammary, Peripheral of adrenal
In G6PD deficiency, NADPH production is compromised, with trigger like SPINF:
Sulfa drugs
Primaquine (malaria)
Infection
Nitrofurantoin (UTI)
Fava beans
Free radical damage RBC Hb, (Heinz body), which is removed by macrophages in spleen (Bite cell), causing anaemia.
167
Rate limiting enzyme of TCA cycle? (1)
Steps of NADH production? (3)
Step of FADH2 production? (1)
Isocitrate DH
NADH is produced when Substrate is:
1. Isocitrate
2. alpha-Ketoglutarate
3. Malate
FADH2 is produced when Product is:
1. Fumarate
168
Name the 10 essential A.A. (10)
Name the 3 basic A.A. (3)
Name 2 ketogenic & 3 glucogenic A.A. (5)
PVT TIM HALL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine (chile only)
Leucine
Lysine
Her Leggings Are basic
Histidine
Lysine
Arginine
Keto: Lamb & Liver
Leucine
Lysine
Gluco: Honey, Mango, Vanilla
Histidine
Methionine
Valine
169
State the derivatives of Phenylalanine/Tyrosine, Tryptophan, Histidine, Glycine, Glutamate & Arginine. (6)
Patient has maple smell urine, why? (1)
Phenylalanine/Tyrosine: Dopamine, NE, E
Tryptophan: Niacin & NAD+ , Serotonin & Melatonin
#Hartnup disease & pellagra
Histidine: Histamine
Glycine: Porphyrin & Heme
Glutamate: GABA , Glutathione
Arginine: Urea, Creatine, NO
MSUD due to defective BCAA metabolism
[Valine, Leucine, Isoleucine]
170
Briefly describe urea cycle. (5)
Ornithine transcarbamylase deficiency leads to accumuation of? (3)
Name 2 clinical signs of high AMM. (2)
Patient has high AMM, how to treat them? (3)
Rate-limiting: CPS1
1. NH3 + CO2 [CPS1] >> Carbamoyl Phosphate
2. +Ornithine = Citrulline
3. +Asp & ATP = Argininosuccinate
4. Arginine, & Fumarate (>>TCA)
5. Ornithine, & Urea
Orotic acid, CP & AMM
1. Asterixis
2. Cerebral edema
Treatment
1. For patient with enzymatic deficiency in urea cycle, suggest dietary protein restriction
2. For patient with urea cycle compromised due to liver failure, give lactulose (increase GI excretion) & rifaximin (decrease colonic production)
171
How fat-soluble vitamin works? (4)
D: Liver for storage, Kidney for activated.
Distal tubule, Duodenum, Destroy Bone
A: Antioxidant, Aura, Activation (Epithelial cell), Alopecia & Abnormal pregnancy
K: gamma carboxylation for 2,7,9,10,C,S ; Not in milk
E: Prevent FA peroxidation & thus arteriosclerosis
172
Ethanol, hypoglycemia, ketosis, lactic acidosis, what is the common etiology? (1)
What is the difference between fomepizole & disulfiram? (1)
High NADH/NAD+
Ethanol to Acetylaldehyde requires NAD+
Gluconeogenesis requires NAD+
TCA cycle requires NAD+
Pyruvate to Lactate uses NADH
Fomepizole prevents formation of Acetylaldehyde to treat Ethanol intoxication. Disulfiram prevent metabolism of Acetylaldehyde to discourage Ethanol consumption.
173
Heme synthesis? (1)
Where the reaction take place? (2)
Describe how sideroblastic anaemia, Pb, AIP, & PCT related to Heme synthesis.
Get Some Additional Points Having Understood the Correct Pathway for Heme.
Glycine
Succinyl CoA
ALA
Porphobilinogen
Hydroxymethylbilane
Uroporphyrinogen
Coproporphyrinogen
Protoporphyrin
Heme
Going A LA cytosol
Cop me some mitochondria
AS: SA (sideroblastic anaemia)
LErrochelatase & ALA Dehydratase: LEAD
#basophilic strippling, lead lines, burton lines.
PD: AIP
#5P's: Pain, Polyneuropathy, Port wine urine, P450 inducer (cause), Psychological
UD: PCT
#Photosensitivity
174
Name 4 drugs that inhibit purine synthesis
Purine: R5P >> PRPP >> 5PRA >> IMP >> AMP/GMP
Overall: Azathioprine, 6-Mercaptopurine
IMP to GMP: Mycophenolate, Ribavirin
175
Name 4 drugs that inhibit pyrimidine synthesis
pyrimidine: Glutamin+CO2 >> CP >> Orotic acid >> UMP >> UDP >> dTMP / CTP
CP to Orotic acid: Leflunomide
RNR: hydroxyurea
TS: 5-fluorouracil
DHFR: Methotrexate
176
Name 1 condition related to purine salvage pathway. (1)
Lesch-Nyhan syndrome (HGPRT deficiency) causing high UA
Purine salvage:
APRT: A to AMP
HGPRT: H & G to GMP
else: X >> UA
177
Name 3 conditions related to Catecholamine synthesis. (3)
CAT:
Phenylalanine >> Tyrosine >> Dopa >> NE >> E
#Tyrosine >> Homogentisic acid >> Fumarate
#Dopa >> Melanin
1. Alkaptonuria (HO)
2. Albinism (Tyrosinase)
3. Phenylketonuria (P H / BH4) [avoid aspartame]
178
Explain how folate cycle & activated methyl cycle are closely related, and contribute to 4 other biochemical process. (4)
Folate cycle:
Folate >> DHF >> THF >> 5,10M THF >> 5M THF >> THF
#5,10M THF >> DHF ; dUMP >> dTMP
#5, 10M THF >> Formyl THF : 5PRA >>IMP
Activated methyl cycle:
H >> M >> SAM >> H
#SAM >> CAT
#H >> succinyl CoA >> TCA
Relationship:
5M THF >> THF ; H >> M
