Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
279 Cards in this Set
- Front
- Back
|
Sources of variation in labs
|
Analytical (pre,analyitcal,post), Biological (within individual, between individuals)
|
|
|
Precision : Types, Formula
Accuaracy : def. , formula |
Measure of repreducibility, by repeated analysis (n=15-20). Types : Within batch variation, day-to-day variation. Formula --> CV = SD x 100/mean.
Accuaracy : deviation from true valeu --> 100(xtag-xtarget)/xtarget |
|
|
Important limits other than the reference limit
|
Medical descision limit (optimal cut-off), Risk limit, Panic value
|
|
|
Sensitivity ?
Specificity ? Efficiency ? |
Sensitivity - incidence of positive results from all those truly with the disease, TP/TP+FNx100.
Specificity : Incidence of true negatives among all those really without the disease --> TN/TN+FPx100. Efficiency : true results from all tests (TP+TN/total) |
|
|
4 Factors affecting plasma enzyme activity. Give 2 half-lives of enzymes in serum
|
1. Rate of release from cells
2. Volume of distribution 33. Rate of removal, metabolism 4. Presence of inhibitors of activators of the enzyme in plasma. Half-lives : CK --> 1.4days GPT --> 6.3days |
|
|
International unit of enzyme activity (Def, units)
|
Amount of enzyme wich under given conditions will catalyse the conversion of 1micromol of substrate per minute. 1IU = 16.7nkatal. Katal is mol/s (!!! MOL, not micro ! huge amount)
|
|
|
Causes of cell-injury, also - consequently released substances ?
|
Cell injury - Hypoxia, drugs, physical damage, microbio, immune, aging, nutrition. Substances : First pump failure --> ions.
Second metabolites imbanalces --> metabolites, lacatate. Third membrane damage --> enzymes, proteins |
|
|
Classical PKU (which family of diseases, whcih enzymes, cc in plasma)
|
Hyperphenylalanineemias, Phenylalanine hydroxylase. Cc > 2mg/dl
|
|
|
Phenylketonuria (incidence, symptoms, dx, tx)
|
Incidence : AR, 1:10,000
Symptoms : IQ < 20 Lab : Guthrie test, plasma Phe, prenatal DNA analysis. Tx - low-phenylalanine diet, gene therapy |
|
|
Prenatal dx of inherited AA (when, how)
|
When - previous child with disease, parents, relatives are known to have
How - amniotic fluid sampling --> culturing of cells --> chorion villi sampling for gene analysis |
|
|
Tyrosinemia (types, problem, sx). Alkaptonuria (what accumulates, sx)
|
Tyrosniemia I --> se/ur tyrosine increased, DOPA increased, Methionine increasd, hepatic failure
Tyrosinemia II --> IC tyrosine crystals, eye lesions, Methionine normal. Alkaptonuria --> HGA accumulates, binds to collagen. Sx - degerenatve arthritis, pigmentations in ears |
|
|
Cystinuria (incidence, disorder, sx, dx, tx)
|
Incidence - AR, 1:7000
Disorder - renal absorption of cystine,lys,arg Sx - renal stones, failure Dx - cysteine stones in urine, HPLC for AA in urine Tx - large water urine, alkalizing the urine |
|
|
Homocystinuria (incidence, enzyme def, sx, dg, tx)
|
Incidence - AR, 1:200,000
Def : Cystathion B Synthase Sx - Homocystiene increased, toxic to endothel. Cystine decreases, damages collagen metabolism. Dx - Guthrie test for methionine, HPLC, Tx - low-met, vitamin co-factor (Pyridoxine) |
|
|
Possible source of error when testing newborns for homocystinuria ?
|
Checking before 3 days of life (too early)
|
|
|
Two enzymes defect in urea-cycle disorders (also, sx, dx)
|
1. Carbamyl-phosphate-synthetase
2. Arginase Sx - vomiting, liver failure Dx - plasma ammonia detection, plasma enzyme detection |
|
|
CF dx --> sweat test (elevated?)
|
>60mM Cl- (40-59borderline)
|
|
|
3 galactose metabolic disorders (incidence, enzyme, sx, dx)
|
1.Galactokinase def : 1:40,000, mild, galacticol deposition in lens -->cataracts. Dx - no galactokinase in RBCs
2.Galactose-1-P-Uridyltransferase def. 1:60,000, poor growth, jaundice, cirrhosis, cataracts, mental. Dx - galactose in urine, enzyme detection in RBCs. 3. UDP-galactose-4-epimerase def. rare, RBC galactose1P is elevated (either mild or severe) |
|
|
3 Fructose metablic disorders (incidence, enzyme, sx, dx)
|
1. Hereditary fructose def :
rare, Fructokinase def, harmless, fructosuria 2. Hereditarty fructose intolarance : 1:40,000, Fructose-1P-Aldolase def, sx - hypoglycemia after fructose, liver failure. Dx - enzyme defect in liver biopsy sample. 3. Hereditary fructose 1-6-diphosphate def : sx - apnoe, hyperventiliation, hypogylcemia, lactic acidosis (impaired gluconeogenesis). Dx - enzyme defect in liver biopsy |
|
|
Glyocgenosis - Type I, Type II, Type III
|
Type I - Von Gierke - Glucose-6-phosphate
Type II - Acid-alpha-glucosidase def. Accumulation of lyosomal glyocgen. Herat/skeletal muscle weakness, cardiomegaly ,hepatomegaly. Pompe (IIa) - respiratory failure, death in 1y. Dx - enzyme activity in muscle. Type III - Amylo-1-6-glucosidase def, Cori disease, debranching def, abnormal gylcogen stored. Sx like type I --> Hypoglycemia, hyperlipidemia,hyperuricemai. DD - Hyperglacaemic response to galactose (?) |
|
|
Defects in lipid metabolism, mention ?
|
Disorders of mitochondrial fatty acid oxiddation, disorders of very long chain fatty acids, lipid storage disorders, lipid metabolism and transport disorders
|
|
|
Disorders of very long chain fatty acids (Peroxisomal disorders) - Incidence, what is peroxisome, classification, sx
|
1:50,000. Peroxisome is a subcellular organelle with 80 enzymes that are imported there. Stores AA, H2O2 and lipid enzymes. Classification - Disorders of perixosome biogenesis, abnormal perixosomes (at least 2 enzymeS), single enzyme defects, normal peroxisome. Sx - cirrhosis, neuronal migration defects, catartacts
|
|
|
Positive APR, Negative APRs
|
Early - Alpha1AT, Haptoglobin, Fibrinogen, CRP. Late- Ceruloplasmin, C3,C4. Negative :
Prealbumin, Albumin, Transferrin |
|
|
Roles of acute phase proteins
|
Inhibition of destructive proteases, scavenger prteins, aid in inflammatory reaction (phagocytosis), wound healing
|
|
|
3 fetaures of CRP, when is CRP increased
|
Features - 1. Reacts with C-polysaccharide of Strep pneumonia but binds other many bacteria, fungi, etc
2. Migrates to between gamma to mid-beta regions on electropherosis 3. Opsonization, activation of complement. CRP is increased is infalmmation, necrosis, infections, and malignancies |
|
|
Procalctionin assay - where produced, when increased, clinical use
|
Produced by extrathyroid tissues, increased in sepsis and bacterial infections. Uses - ARDS, etiology, monitoring effectivness of therapy and prognosis
|
|
|
Types of tumor markers
|
Enzymes, isoenzymes, hormones, oncofetal antigens, carbohydrate epitopes, receptors, TSGs, oncogenes
|
|
|
Tumor markers used for screening (remember that most other markers have low sens/spec, and low predicitve values)
|
VMA/HVA --> Neuroblastoma
PSA CA125 --> Ovarian cancer, most frequent cancer in women, only in familial predisposition. AFP - Hepatocellular cc (every 3-4months). HCG - choriocc - best tumor marker, extremely sensitive. Calcitonin --> Medullary thyroid cc, every year. |
|
|
Germ-cell tumors (Seminoma, Nono-seminoma). Ovarian tumor, cervical cc
|
Seminoma - AFP. Non-seminoma hCG. Ovarian cc - CA125, Cervical cc - SCC
|
|
|
Lung tumors markers, breat cc, prostatic cc
|
Lung - Adenocc CEA, Cyfra 21-1. Lung - SCC Cyfra21-1 SCC. Lung SCLC - NSE. Lung Large cell - Cyfra 21-1, CEA. Breast - CA 15-3, CEA. Prostate - PSA, fPSA/tPSA
|
|
|
GI tumor markers. Prognostic markers
|
Colorectal - CEA
Stomac - CEA, CA19-9 Esophagus - SCC, TPA PAncreas - CA 19-9. Prognositc markers - AFP,hCG for nonseminoma, PSA for prostate, CA125 for ovarian cc, CEA for coloretal, CA 15-3 for breast |
|
|
When to check for tumor markers ?
|
-Before first therapy
-2-10 days after therapy -1st,2nd year every 3 months -3-5th year every 6 months -before change of theray -under suspicion of relapse -2-4 weeks after a significant increase |
|
|
Iron : total, precent in ?
|
Total iron 3.5-5g. ~70% in hemoglobin, ~25% in ferritin storage, ~4% in myoglobin. Plasma iron 3-4mg
|
|
|
When is sTfR not a useful indicactor ?
|
When there is increased eryhtroid activity in the BM
|
|
|
Transferrin saturation values
|
Normal - 15-45%
Iron def - <15% Iron overload - >60% |
|
|
Two mutations in type I HH. Type II ?
|
HFE gene, chr. 6 :
1 - C282Y - no sensing of circulating iron, no DMT downregulation 2 - H63D, might affect Tf-TfR binding. Type II HH - Hepcidin gene |
|
|
Where is iron stored in HH
|
1. Tissue mac's and other MPS cells
2. RES system, heart, endocrine. Causes lipid peroxidation and DNA damage |
|
|
Two types of hemoglobinopathies
|
Qualtitative (HbS,...) --> Diagnosed by electrophoresis
Quantitative (Thalassemia) |
|
|
HbS - mutation, dx
HbC - mutation, dx HbE - Mutation, dx |
HbS - Val for Glu in 6 of Beta chain. Dx - Electrophoresis, sickle cells
HbC - Lysine for Glu in 6 of Beta chain. Dx - target cells, spherocytosis, bilirubin increase, rhomboidal shaped cells. HbE - Lysine for Glu in 26 of B. Electorp, target cells |
|
|
Alpha thalassemia - HbH disease (genes, dx)
|
Alpha0-Alpha+ (1 gene normal only). Beta chain accumulation, Beta4 tetramers formed --> inclusiong in RBCs.
Dx - Electrophoresis (beta4), hypochromic, microcytic, target cells. Golf-ball cells in brillian-cresyl blue, preceptated B-chains |
|
|
Dx of hereditary spherocytosis
|
1. Clinical : splenomegaly, jaundice, anemia
2. Smearl : microsphearocytes, reticulocytes 5-20% 3. Increase autohemolysis corrected by glucose 4. Increase osmotic fragility 5. Cr51 studies - splenic destruction |
|
|
Dx of G6PD Def
|
Clinical : intravascular hemolysis
-Direct enzyme assay -Heinz bodies, bite-and-blister cells on film |
|
|
Two processes requiring Vit B12
|
1. Homocysteine to Methionine transformation
2. Methyl THF to THF -->necessary for Purine synthesis |
|
|
Clinicla signs of megaloblastic anemia
|
Pallor, mild icterus, glossiti, angular cheioosis.
Smear - macro-ovalocytes, hypersegmented granulocytes. Schilling test. AutoAb in case of Corpus AI gastritis. Serum B12/Folic acid assays Megaloblasts in BM |
|
|
Thrombocytopenia - what to mention
|
Decreaed production, accelerated destruction, abnormal destribution, loss from body.
|
|
|
Thrombocytopenia - decreased production - what to mention
|
1. Congenital (TAR, May-Heggelin)
2. Neonatal (Rubella, Thiazides in mother) 3. Acquired |
|
|
Thrombocytopenia- increaesd dstruction, acquired
|
1. Drugs, radiation, aplastic anemima, viral (rubella, cmv). Lymphoma, myeloma
|
|
|
Thrombocytopenia numbers in ITP, Drug-induced, and in TTP
|
ITP - 10-50g/L
Drug induced < 10g/L TTP - <20g/L |
|
|
1. Dx criteri for Acute leukemia
2. Assays used in DD of leukemias 3. Myelopoesis steps |
1. >=20% of blasts in BM
2. Hematology analyzers blood count, Smears, cytochemistry (GAPA, MPO, Sudan black..), ESR, Immunophenotyping, FISH, Molecular biology 3. Myeloblast, Promyelocyte, Myeloyte, Stab, Neutropihil |
|
|
1. Eryhtropoeisis
2. Differences between myeloblasts and lymphoblasts |
1.Proerythroblast, erythroblast, basophil erythroblast, polychrom erythroblast, orthochrom erythroblast, reticulocyte, rbc
2.Myeloblasts --> granulation, wider cytoplasm |
|
|
1.CD marker sof myeloid cells
2. CD markers of lymphoid cells |
Granulocytes - MPO, CD13, CD15
Monocytes - CD14, CD13 Megakaryoctes - CD41, CD42, CD61 Erythroids - Glycophorin A, CD71 Pan-leukocyte marker - CD45 Stem cell marker - CD34, CD117 2. T cells - CD2/3/5/7/4/8 B cells - CD19,20(mature),22, CD10(immature) NK cells - CD16, CD56 |
|
|
1. FAB classification of ALL
2. Markers in ALL 3. Frequency of ALL subtypes |
L1 - small blasts cells ,high nuclear-to-cytoplasm ratio, homogenous chromatin
L2 - Larger blasts , prominent nucleolos, lower nuclear-cytoplasmc ratio L3 - Middle-large vacuolated blasts, basophilic cytoplasm. Burkitt. 2. Pro-B CD19, CD10- Pre-B CD19,CD10+, miu chains B-ALL - sIg 3. Childhood - 80% L1 Adults 60% L2 |
|
|
Prognostic markers in ALL
|
Favorable - t(12;21) in cALL
Favorable -HYperdiploid Favorable - age 2-10 Unfavorable - CD10- Unfavorable - L3 |
|
|
1. Which AML shows Auer rods
2. Which AML shows azurophilic granulatio ? 3. Which AML is associated with DIC |
1. M1 (few), M2-M3
2. M1-M2-M3 3. M3 |
|
|
1. What is the most frequeny AML
2. What are the cytochemistry staining used for AML 3. What is the cytochemistry staning of M4/M5 |
1. M2
2. MPO, Sudan black 3. Non-specific esterase NSE |
|
|
What are the prognostic markers in AML ?
|
Favorable t(8;21) in M2 or inv16 in M4. Ph chr unfavorable.
Unfavorable age is <2 or >60 |
|
|
1. Does CLL transform into ALL ?
2. Dx of CLL |
1. No.
2. Leukocytosis, lymphocytosis (5x10^9/L), Gumprecht shadows , Low Ig, uric acid increased, Lymphocytic inf of BM |
|
|
1. Immunophenotyping of B-CLL (96%)
2. Cytogenetics of B-CLL |
CD19, CD20, CD22, CD5(!!), CD23.
2.Cytogenic - +12, t(11;14), 17p13 del. |
|
|
1. Origin of PLL
2. Morphology of PLL 3. Immunophenotyping of PLL |
1. ORigin is CLL
2. Less mature lymphoid cells with nucleoli 3. CD20, CD22, FMC7 |
|
|
1. HCL cytochemistry
2. HCL immunophenotyping |
1. TRAP
2. CD103, CD25, CD11c + other B cell markers |
|
|
Dx of MM
|
Hypercalcemia, renal insuff, URic acid increased, Beta2 microglobulin increaed (prognositc!), total IgG increaed, monoclonal bands on electrophoresis
|
|
|
CML :
1. Which lines does it affect 2. Genetics 3. special |
1. Myeloid, eryhtoid, megakaryocytic
2. Ph chr 9;22 (bcr-abl TK) 3. Transforms into AML or ALL ! During blast crisis 2/3 have AML 1/3 have ALL |
|
|
Dx of CML (bc, diff, bm, cytochemistry, genetics)
|
BC - Anemia, Leukocytosis, thrombocytosis
Diff - granulocytic maturation with basophilia,eosiniophilia BM - hypercellular with myeloids Cytochem - decreased GAPA score Genetics - ph chr in 96% |
|
|
GAPA should be checked at which pH? also, what does it check for ? also, what is the score for CML ?
|
Check at alkaline pH, check for secondary granules in neutrophils. CML <20
|
|
|
MDS :
1. which lineages are affected 2. Clinical 3. Transformation 4. dx |
1. All 3 myeloid lineages (eryhtroid, plt, monocyte/granulocytes) may be affected
2. Cytopenia (anemia, infectiosn, bleeding) 3. Transforms in AML 4. Dx is by abnormal morphology and dysplatic changes in BM |
|
|
Specific morphological changes in BM in MDS
|
RBC - ring sideroblasts, erythroid hyperplasia
WBC - hypogranulation of graulocytes, PLTs - micromegakaryocytes |
|
|
Hemophilia grades
|
Mild - 5-30% of the factor
Moderately severe - 1-5% Severe - <1% |
|
|
1. Symptoms of Afibrinogenemia
2. Symptoms of dysfibringonemia |
1. Severe bleedin diathesis and plt function, spont abortion
2. 25% hemorrhages, 25% thrombosis, 50% asympt |
|
|
5 acquired coagulopathies
|
1. Neutralizing/non-neutralizing Ab
2. Non-Ab inhibitors (Heparin) 3. Liver disease 4. Vit K def (also Comuarin/Warfarin/Cephalosporin) 5. Consumption coagulopathies |
|
|
Platelet disorders - 5 causes
|
1. Quantitative
2. Adhesions defects 3. Aggregation defects 4. Secretion defects 5. Defect of procoagulant acitivty |
|
|
Disorders of plt adhesion.
Defects of plt aggregation |
1. vWD
2. Bernard-soulier syndrome (GP Ib-Ix complex) 3. Collagen receptor defect (GP Ia-IIa cmplex) Plt aggregation : 1. ADP receptor defect 2. Afibrinogenemia 3. Glanzmann thrombosthenia |
|
|
1. Functions of vWf
2. Dx of vWD |
1. Plt adhesion to collagen and other subendo structures
2. Plt aggregation 3. Associates with and protects factor VIII Dx of vWD : 1. Bleeding time 2. PFA-100 3. vWF:Ag, vWF:RCo 4. RIPA 5. vWF gene analysis |
|
|
Which two integrin receptors does vWF bind to ? by which sequence ?
|
Binds vWF receptor (GP Ib-Ix) and Fibrinogen receptor (GP Ia-IIa) by the RGD sequence on the vWF
|
|
|
Five types of vWD.
Which ones are AR ? |
Type I - Partial qunatitative def, multimers normal
Type IIa - absence of largest multimers. Low levels of vWF:RCo Type IIb - low level of large multimers. vWF:RCo normal, enhanced RIPA Type IIn - defective binding of vWF to FVIII. Low FVIII Type III - absent plt and plasma vWF. Severe bleeding. Types IIn and III are AR |
|
|
Two special features of vWD ? Also, what chr is vWF on ?
|
1. Blood group O have lower vWF levels. Most vWD patients have O blood.
2. Type I cannot be detecetd by genetic testing. vWF is on chr 12 |
|
|
What suggests thrombophilias ?
|
1 DVT at a young age
2. Recurrent thrombosis 3. Familial recurrence |
|
|
Give 4 causes and one example each of inherited thrombophilias
|
1. Def. of inhibitor --> AT-III def
2. Def. if an inactivator --> Protein C def 3. Impaired fibrinolytic activity --> Plasminogen def 4. Elevated factor level or abnormal factor --> APC |
|
|
What is the incidence of AT-III def, what are its symptoms, and what are its two types
|
AD, 1:2000-1:5000, Sx - DVT, PE, CVT --> Only heterozegous, homozegous dead. Two types - Type I --> Low AT activity and antigen, Type II --> Abnormal molecule
|
|
|
What are 3 tests used for AT-III def, and how do you diff type I from II
|
3 tests : 1. Funnctional tests (AT activity/Anti-FXa test), 2. Determination of ATIII antigen (turbidometry), 3. Examination of Heparin binding.
Type I shows decreased antigen, type II shows normal antigen |
|
|
How do you check for Protein C or PRotein S def, also, what is a special form of acquired Protein S def ?
|
Tests : clotting tests, ELISA for antigen. Pregnancy can lead to an acquired Protein S def.
|
|
|
APC resistance,FV Leiden : What is FV a cofactor of, where is the mutation, what is the result, what is the thrombosis risk ?
|
FV is a cofactor of Factor X, the muation is a guanine-adenin exchange at nucleotide 1691 resulting in Arg506Gln which cannot undergo proteolysis by APC. Risk is 5x in hetero, 80x in homo
|
|
|
How do you check fo APC res or FV leiden ? What is the functional test of APC res ?
|
APC Res - clotting tests,
FV leiden - molecular genetics. Functional test : testing APTT in the presence of APC and without it. The ratio of APTT+APC / APTT should be >=2 |
|
|
What is the PT 20210A allele mutation ? how much is the thrombosis risk increased, what is the incidence ?
|
Mutation in 3' UTR of the PT gene results in increased translation and more stable RNA of PT. Risk is 2-4x. Frequency is 1.7% in caucasians
|
|
|
Give 3 causes of acquired thrombophilias. Give 3 malignant diseases with thrombotic complications.
|
1. Malignant diseases
2. APS 3. HIT Diseases : AML M3, Primary brain tumors, Pancreas cc |
|
|
Give 2 factors inducing hypercoaguability in malignancies
|
1. Host response (APR, neovascularization, necrosis, abnormal protein metabolism), 2. Malignant cells features (TF expression, Cystein proteases activate FX, expression of plt activators)
|
|
|
1. What is APS
2. What are its two types 3. What is the clinical criteria for APS |
1. An autoimmune condition in which a grouop of anti-phospholipid Ab play a role in pathogenesis of thrombosis
2. Primary APS (idiopathic), Secondary APS (SLE, Neoplasis, others) 3. Criteria : vascular thrombosis and pregnancy morbidity |
|
|
What are the lab criteria for APS, how do you detect them ? what are the Ab in APS really against ?
|
Lab criterai - Lupus anticogulant, Anti-cardiolipin Ab, Anti-B2 glycoprotein. You detect these using ELISA. The Ab are really against Beta2-glycoproteinI and PT --> their epitopes become exposed when they bind phospholipids
|
|
|
What is LA, what is the result in vitro and in vivo, and how do you diagnose it ?
|
LA - IgG/IgM that interfere with phospholipid-dependent clotting tests. In vitro anticoagulant, in vivo --> thrombosis. Tests - APTT prolongation, mixing studies, correction by phospholipids increase, immunoassays
|
|
|
Give 4 types of consupmtion coagulopathies
|
1. Acute DIC, 2. Large thrombus, 3.Primary hyperfibrinolyiss, 4.Thrombolysis
|
|
|
Give 4 causes of acute DIC, also what are the two stages of DIC
|
Causes : 1.Acute obstetric complications, 2. Sepsis, 3.,Tumors, 4.Snake bite
Stages of DIC : 1.Thrombotic phase, 2.Hemorrhagic phase(consumption) |
|
|
Give 4 tests included in the DIC panel
|
1. PT/APTT/TT
2. Plt count 3. Tests indicating activation of coagulation and fibrinolysis --> D-Dimer 4. Tests indicating consumption of inhibitor --> AT-III 5.Fragmentocytes |
|
|
Give 3 causes of primary hyperfibrinolysis, and also what is the main lab difference between DIC and primary hyperfibrinolysis (as they are both consumption coagulopathies)
|
Causes of priamry hyperfibrinolysis : 1.Prostate cc, 2.AML M3 (Plasminogen activator), 3.Cirrhosis.
Main difference between DIC and primary hyperfibrinolysis is that only in primary you have FDP, and all other tets (AT-III, Plt count, Fragmentocytes) are normal in primary |
|
|
What are 4 tests used to estimated GFR ?
|
1. Clearance
2. Plasma Creatinine 3. Plasma Urea 4. Plasma level of low molecular weight proteins (Beta2-microglobulin, Retinol-binding protein, Cystatin C) |
|
|
Give 3 formulas to eastimate clearance, also give the GFR of various levels of renal failure
|
1. Cockroft-Gault : (140-age)xBM / (SCrx72)(x0.85 if female)
2. MDRD --> complicated, only in patients suffering from renal disorders 3. Quadratic formula. None of the formulas is valid for <18years and pregnant women. GFR in renal failure : 60-90ml/min --> Mild 30-60 --> middle 15-30 --> Severe <15 --> end-stage |
|
|
What is the reference interval for Plasma creatinine, what happens to it in the kidney. Same for Urea
|
SCr : men-80-115micromol/L, women-53-97. Creatinine is slightly secreted in the tubules.
Urea : 2.9-8.2mmol/L. Some passive reabsorption in the kidney |
|
|
What is the daily proteins amount in the glomerular filtrate, how much is excreted, how much albumin, and 3 causes for Proteinuria
|
Proteins in filtrate : 7-10g/day. Urinary protein excretion : <150mg/day. Albumin : <30mg/day.
Causes for proteinuria : 1. Incresed filtered load, 2.Decreased tubular reabsorption, 3.Postglomerual secretion or leakage |
|
|
Dip-stick test for albuminuria, what is its lowest range, when does it give FP results. Also, how do you diff causes of protein uria by electrophoresis
|
Lowest senstivity for dipstick test for albumin is 200mg/L. FP is when urine is alkalic or with X-ray contrast media. Proteinuria due to tubular dysfunction would show Low-Mr proteins, glomerular would show high
|
|
|
Give 4 tets for the assessment of tubular function
|
1. Renal concentration ability (water deprivation)
2. tests for renal tubular acidosis (bicarbonate excretion) 3. tests for aminoaciduria (HPLC) 4. Glucose in urine |
|
|
What is the definition of ARF, give 4 signs
|
Rapid decrease of renal function characterized by electrolyte, acid-base, and fluid imbalances. Signs - GFR decrease, Uremia, Disorders of urine volume, Hematuria/Proteinuria
|
|
|
What are the 3 types of ARF >
|
Prerenal, renal(intrarenal), postrenal
|
|
|
What are the changes seen in prerenal ARF, and what are the differences from intrarenal ARF
|
Changes in prerenal : RBF decreases-->RAS activates, ADH increases, Decreased GFR leads to acidosis and hyperkalmia due to lower load of Na reaching distally.
Diffrences from intrarenal : 1. Urinary Na>40 in intrarenal, <20 in pre 2. Urea content in urine is high in prerenal, low in intrarenal 3. Urine osmolality high in prerenal, low in intrarenal Intrarenal usually tubular necrosis |
|
|
Give 3 indications for hemodyalisis. Also what is the definition of Chr. renal failure and what are its stages
|
1. Plasma K>6.5
2. Fluid overload 3. Plasma urea/creatinine >500micromol/L. Chr renal failure : progressive irreversible impairment of renal function(decrease in functioning nephrons). Stages --> 50-75%, decreased renal reserve, 25-50% - renal insuff, 10-25% renal failure, 0-10% end stage |
|
|
Give 4 features of uremia
|
1. Impairment of concentration and dilution
2. Acid-base, electrolytes imbalances 3. Waste products retention 4. Decreased calcitriol,EPO |
|
|
Give 2 renal tubular . Also, define Fanconi syndrome
|
1. Fanconi syndrome
2. RTA. Fanconi --> Generalized disorder of proximal tubular function leading to glycosuria, AAuria, phosphaturia and acidosis (RTA 2) |
|
|
Give 3 causes of Fanconi syndrome, also what are the types of RTA
|
Fanconi causes :
1. Idiopathic inherited (cystinosis, Wilson) 2. Nephrotoxins 3. Amyloidosis RTA : RTA-1 - distal RTA-2 - Proximal RTA-3 - Combined RTA-4 - Aldosterone def |
|
|
RTA-1 : 2 causes, what is impaired, urine pH
RTA-2 : 2 causes, what is impaired, urine pH |
CAuses : 1.Familial, 2.Drugs-Gentamycin. Acidification of urine in the distal tubules is impaired, urine pH>5.5.
RTA-2 : Idiopathic, Wilson, Proximal bicarbonate reabsorption is impaired. If plasma HCO3- normal there is significant loss and urine pH>5.5. However if severe acidosis and HCO3- very low, it is reabsorped and urine pH can be <5.5 |
|
|
Define acid, define base, what is the problem with acid-base measurements ?
|
Acid = proton donor, base = proton acceptor. The problem is that we cannot measure the IC pH, only EC
|
|
|
What are the mechanisms of maintaining a constant pH ? Also, give two IC buffering systems and two EC buffering systems
|
1. Buffering
2. Removal of protons by quick respiration and kidney function. IC buffers : Hemoglobin, organic phosphates. EC buffers : Bicarbonate-carbonic acid and inorganic phosphates |
|
|
What is the anion gap, what is its normal value, and give an example when it's increased
|
Anion gap = (Na+K) - (Cl-HCO3). Normal value is around 15. In lactic acidosis or ketoacidosis it will be increased is HCO3- will be consumed.
|
|
|
Where do you take blood for blood gas analysis ? What is the normal pH, what is the normal PCO2, what is the normal PO2, What is the standard/actual bicarconate, what is the normal Base excess, What is the normal buffer base
|
Use radial or femoral artery. Normal pH 7.35-7.45. PCO2 34-46, PO2>60, Standard bicarbonate 22-26, Buffer base 45-52, BE = -2.5 - +2.5. Bicarbonate compensation = BEx0.3xBW
|
|
|
Predominant water depletion (hypernatremia) - two causes
|
1. Loss of fluid with Na concentration lower than that of plasma
2. Deficient water intake Both can occur due to failure of homeostatic mechanisms or in the presence of normal ones |
|
|
Give 4 causes for predominant water depletion with normal homeostatic mechanisms. Also give 3 causes for predominant water depltion due to failure of homeostasis
|
Excessive water loss : sweating, vomiting,
Deficient water intake : inadequte supply, mechanical obstruction. Failure of homeostasis : Inadequate response to thirst, diabete insipidus, osmotic diuresis |
|
|
How would you diff if the water depletion is due to normal homeostasis or not ?
|
In normal homeostasis you'd have oliguria and concentrated urine
|
|
|
Isoosmolar volume depletion : 2 causes, 3 consequences
|
Causes : 1. loss of SI secretions (fistula, obstruction, paralytic ileus), 2. Tubular damage with normal glomerual function (such as recovery phase of ARF). Consequences : Hypovolemia leading to : 1.Hemoconcentration, 2.Hypotension, 3.Uremia (not in case of ARF)
|
|
|
2 Options for side effects of volume replacement therapy in case of isoosmolar volume depletion
|
1. Replacement fluid has too low Na --> Predominant Na depletion
2. Repleacement fluid has too few proteins --> redcued oncotic pressure, increased hydrostatic pressure --> Edema --> Increased loss of fluid ! |
|
|
Predominant Na depletion - 2 causes
|
1. Volume replacement with fluid of incorrect composition (hypoosmolar fluids)
2. Failure of hemostatic mechanisms of Na(Addison, Pseudoaddison) |
|
|
What is the chain of events of volume replacement with incorrect composition causing predominant water depletion ?
|
Hyopnatremia --> ADH down, Aldosterone up --> Loss of fluid --> Hypovolemia with normonatremia. Only when the sodium is stabilized water homeostatic will be in play and hypoosmolality and urinary sodium loss will occur
|
|
|
What are the clinical signs of predominant Na depletion due to failure of homeostasis (Addison) ?
|
1. Volume depletion
2. Hemoconcentration 3. Mild uremia 4. Late hyponatremia , high urinary Na |
|
|
Give 3 causes for predominant water excess
|
1. SIADH
2. Oxytocin infusion 3. Psyochgenic polydipsia |
|
|
What is the main reason for predominant Na excess. What is different in the lab findings of primary / secondary aldosteronism ?
|
Main cause of predominant Na excess is Aldosteronism.
In 2nd aldosterinsm you find normonatremia or mild hypo, in primary aldosteronism plasma Na is at the upper reference range. |
|
|
How do you monitor volume requirements ? how do you monitor hyper/hypo natremia, What does hypernatremia indicate ? what does hyponatremia indicate ?
|
Volume requirement - monitor urinary Na
Hypo/hypernatremia - monitor plasma Na Hypernatremia indicates water depletion, hyponatremia indicates water excess or Addison's |
|
|
Give 3 factors influencing the distribution of K between ECF and ICF. Also give 2 causes of ICF-ECF shift and two causes of ECF-ICF shift
|
1. Insulin
2. H+ concentratio 3. Na/K pump. ICF-ECF shift : acidosis, bad Na/K pumping ECF-ICF shift : alkalosis, increased activity of Na/K |
|
|
Give 3 factors affecting K excretion in the tubules
|
1. Aldosterone
2. Na load 3. pH in blood |
|
|
When do you have hypokalemia without K depletion, when do you have hyperkalemia with K depletion ?
|
Hypokalemia without K depletion - ECF-->ICF shift
Hyperkalemia with K depletion - DKA |
|
|
Give 3 causes of Hypokalemia
|
1. ECF-->ICF shift (alkalosis, insluin, diuretics)
2. Reduced K intake(starvation, alcoholism) 3. Loss of K(intestinal-diarrhea, vomiting ,urine-hyperaldosteronism, RTA) |
|
|
Give 4 clinical features of hypokalemia
|
1. Impaired glucose tolerance
2. Muscular weakness 3. Alkalosis 4. low T wave, U wave |
|
|
What are the two types of hyperkalemia ?
|
1. Pseudohyperkalemia
2. True hyperkalemia |
|
|
Give 3 causes of Pseudohyperkalemia, and 3 causes of true hyperkalemia
|
Pseudo - Thrombocytosis, hemolysis, storage of specimen. True - ICF-->ECF shift, increased K uptake, impaired renal secretion of K
|
|
|
Give 3 causes for ICF-->ECF K shift. Also, give 2 causes of impaired renal secretion of K
|
1. Acidosis
2. Insulin def 3. Digitalis intoxication Impaired secretion : 1. ARF 2. K-sparing diuretis 3. ACE inhibitors |
|
|
Give 3 clinical features of hyperkalemia. Also, give 2 ways to treat hyperkalemia
|
1. Paralysis of skeletal muscle
2. Cardiac arrythmias, arrest 3. Tall T wave. Treatment : 1. Glucose+insuli 2. Bicarbonate infusion 3. Ion-exchange resins |
|
|
What are the synthesis steps of insulin ?
|
Preproinsluin --> Proinsulin --> Insluin + C peptide
|
|
|
What are the effects of insulin on blood glucose, blood FFA, protein metabolism. Also, what stimulates insulin secretion and what inhibits it ?
|
Decreases blood glucose, decreases FFA in blood (inhibits lipolysis), facilitates protein synthesis and inhibits catabolism.
Stimulates insuin : elevated blood gluc, AA, Increased plasma K. Inhibits - Fasting, epi |
|
|
Give 4 types of DM
|
1. Type I
2. Type II 3. Exocrine pancrease diseases 4. Gestational DM |
|
|
Three factors in pathogenesis of Type I DM
|
1. Genetic - HLA
2. Environemntal insult (viral mostly, damage to beta cells, immunresponse against beta cells) 3. Autoimmune attack (mostly CD8 cells, some autoAb) 4. Leading to Beta-cell destruction |
|
|
Pathogenesis of type II DM
|
Genetic - mutiple defects (primary beta cell defect, deranged insulin secretion)
Environmental - obesity --> leads to insulin resistance due to downgrading of GLUTs) --> this leads to hyperglycemia --> to beta-cell exhaustion |
|
|
What are the preanalytical problems in DM diagnosis
|
1. Delayed centrifugation : at 20C --> 0.4mmol/L/h reduction in glu
at 4C --> 0.1mmol/L/h reduction 2. sampling during glucose infusion |
|
|
What autoAb can be detected in DM ? What are the cut-off values of fasting glucose
|
Islet cell autoab, Glutamic Acid Decarboxilase Ab. Vales :
normal < 6.1mmol/L IFG 6.1-7mmol/L Diabetes >=7mmol/L |
|
|
Diagnostic values when symptoms are present - also how many measurements are required
|
If symptoms present only 1 measurement required. Fasting plasma >7mmol/L, venous plasma random >10mmol/L, capillary blood random >11.1mmol/L. OGTT >=11.1mmol/L
|
|
|
OGTT - preparation, execution
|
Preparation - 3day unrestricted diet, overnight fasting prior to test
Execution - fasting blood sample, then 75g glucose for adults or 1.75g/kg upto 75g for kids in 250-300ml water over 5 min. Test blood 2 hours after the test. |
|
|
How do you test for glycosuria and what are the two causes of glycosuria
|
Test using the insensitive but specific glucose-oxidase strip. Causes of glycosuria : 1. Plasma glucose >11mmol/L while GFR normal
2. Maximal tubular reabsorption capacity decreased (renal glycosuria) |
|
|
HbA1c - how long back, what is the reference interval. Fructosamine - what is glycated, how long back, refernece
|
HbA1c - 6-8 weeks, 3-6% reference
Fructosamine - glycated albumin, 2 weeks, |
|
|
Monitoring of DM is in order to prevent..?
|
1. Diabetic nephorpathy (check macroalbuminuria, creatinine)
2. Vascular complications (check lipids) 3. Prediction of acute metabolic complications (ketone bodies) |
|
|
Screening and control of microalbuminuria
|
Screening - morning urine, positive is Albumin>=20mg/L or Albumin:creatinine >=2.5mg/mmol.
Control - 24h urine, albumin>30mg/day is positive (20microgram/min). Check every 6 months |
|
|
What are the guidelines for DB monitoring in children ?
|
1.Blood/urine glucose daily :
Blood glu>3mmol/L, fasting<7, postprandial<10 2. Glycated Hb every 3 months, from mean of range to 1-2% above range 3. During infections --> daily urine keton tests |
|
|
Guidelines for pregnancy glucose control
|
Fasting <5.6
Postprandial<8 Glycated Hb - between average and upper limit of range. Not recommened above >10% |
|
|
5 risk factors (Screening) for DM
|
1. >45y, if normal repeat every 3years
2. Obesity 3. Relatives 4. GDM 5. HDL<0.9mmol/L, Tg>2.8mmol/L |
|
|
4 causes of coma in diabetec patients ?
|
1. DKA
2. Hyperosmolal non-ketotic coma (mostly type II) 3. Hypoglycemia 4. CVA |
|
|
3 blood tests in DKA, 2 urine tests
|
Blood - Na/K, Bicarbonate, pH
Urine - Glucose, ketone bodies |
|
|
give 2 causes of K depletion in DM, and 3 causes of Hyperkalemia in DKA
|
K depletion in DM :
1. Osmotic diuresis 2. Enhanced aldosterone due to the hypovolemia Hyperkalemia in DKA : 1. Metabolic acidosis 2. Insulin def 3. Renal insuff |
|
|
How do you diff between ketosis due to DKA or due to fasting ?
|
in fasting --> serum glucose normal or reduced, in DKA --> serum glucose increased
|
|
|
Two important facts about ketonuria
|
1. Most tests do not detect B-hydroxi-buterate (80% of ketone bodies), 2.if GFR low, you can have ketonemia without ketonuria
|
|
|
What are the features of non-ketotic hyperglycaemic coma, and why does it occur
|
-Type 2 DM
-Hyperglycemia, extreme dehydration and osmolality -Occurs because there is some insulin to prevent exceesive lipolysis and oppose ketogenic action glucagon --> therefore no ketoacidosis |
|
|
What is the cut-off value for hypoglycemia, what are 2 types of hypoglycemia
|
<2.2mmol/L
Fasting hypoglycemia (morning,after exercise,diseasae), reactive hypoglycemia (after meal, drug, alcohol) |
|
|
give 3 causes of fasting hypoglycemia
|
1. High endogenous insuli (insulinomas)
2. Glucocorticoids def 3. Liver disease |
|
|
Give 3 causes of reactive hypoglycemia
|
1. Drugs - insulin
2. Postprandial 3. Alcohol |
|
|
What are the symptoms of hypoglycemia
|
1. Acute neuroglycopenia - vertigo, ataxia, diplopia
2. Chronic neurglycopenia - altered personality, dementia 3. Sympathetic stimulation |
|
|
Give 3 causes of neonatal hypoglycemia, give 3 causes of infancy hypoglycemia. Also, how would you diff if the cause of the hypoglycemia is endogenous or exogenous insulin ?
|
Neonatal - infants of diabetic mothers, malnutrition, preterm babies
Infants : 1.ketotic hypoglycemia (idiopathic), 2.hyperinsulin (insulinomas), 3.Inborn errors of metabolism(glyocgenosis). It the cause is endogenous you woud also have elevated C-peptide |
|
|
Precentage of Cholesterol in Chylomicrons and VLDL
|
Chylomicrons - 8, VLDL-22 (84,50 TG)
|
|
|
Where are chylomicrons produced, VLDL, LDL, HDL
|
CM - In intestine after fat
VLDL - in liver in response to high carbohydrates LDL - at peripheral tissue when VLDL gives up TG HDL - removal of chol from tissues to liver |
|
|
What are the diagnostic methods for Cholesterol, TG, HDL, LDL. Also, what is the fridewald calcuation
|
Chol, TG --> Enzymatic, electrophoresis
HDL - electrophoresis, HPLC, selective precipitation LDL - Fridewald calculation, selective precipiation. Fridewald : LDL = Total Chol - (HDL - (TG/2.2)) |
|
|
What are the healthy limits for chol, TG, HDL
|
Chol - optimal is 5.2mmol/L (200mg/dl)
TG - upper for fasting is 2.2mmol/L (200mg/dl) HDL - lower limit is 0.9mmol/L (35mg/dl) |
|
|
What's present in each type of Hyperlipoproteinemia ?
|
I - chylomicrons
IIa - LDL IIb - LDL + VLDL III - IDL or beta-VLDL IV - VLDL V - VLDL + chylomicrons |
|
|
Hyperlipoproteinemia Type I (Primary - Inheritence, Def in what ?, secondary, sx)
|
Primary - AR : LPL def, APO CII Def, secondary - SLE, DM. Sx - elevated TG, xanthomas, pancreatitis
|
|
|
Hyperlipoproteinemia Type II (Primary - Inheritence, Def in what ?, secondary, sx)
|
Primary - AD (or polygenic in IIb), LDL-synthesis/transport/uptake block or ApoB100 def. Secondary - hypothyroid, obstructive billiary disease. Sx - elevated C, LDL, VLDL(IIb), lipid deposits in BV
|
|
|
Hyperlipoproteinemia Type III (Primary - Inheritence, Def in what ?, secondary, sx)
|
Primary - AR : IDL metabolism, abnormal ApoE. Seconadary - Hpothyroid, SLE, DM. Sx - elevated IDL/VLDL, fat deposits, xanthomas
|
|
|
Hyperlipoproteinemia Type IV (Primary - Inheritence, Def in what ?, secondary, sx)
|
Primary : AD, familial hypertrigclyceridaemia. Secondary - hypothyroid, DM, alcoholism. Sx - elevated VLDL/LDL, glucose intolerance
|
|
|
Hyperlipoproteinemia Type V (Primary - Inheritence, Def in what ?, secondary, sx)
|
Primary : AD - familial hypertriglyceridaemia. Secondary - DM, Alcholosim, pacnreatitis. Sx - xanthomas, elevated chylmicron and VLDL
|
|
|
Hypolipoproteinaemias - low chol, normal or low HDL - 3 causes :
|
1. Abetalipoproteinaemia (lack of B100, lack of LDL,VLDL,CM, ADEK absorption defect)
2. Hypobetalipoproteinaemia (Mutation in ApoB, low LDL/chol, normal VLDL/TG) 3. Chylomicron retention disease (APOB-48 defect, fat malabsorption) |
|
|
Hypolipoproteinaemias - isolated low HDL - 3 causes
|
1. Familal hypoalfalipoproteinaemia (defect in hepatic lipase and ApoA-I/C-III, Low HDL, early CHD)
2. ApoA-I, ApoC-III def 3. Tangier disease (AR, mutation in ATP binding transporter 1 gene - increased HDL degradation. Low HDL, early CHD, orange tonsils) |
|
|
TG : what are the desired levels
|
<20 years of age : <1.1mmol/L. Middle-age <1.7, Significant abnormalities when >2.2mmol/L. 2.2-4.4 --> evaluate for other risk factors. 4.4-11 --> usually hypertriglyceridaemia
|
|
|
3 Complications of severe hypertriglyceridemia, and 3 risk factors associated with it
|
Complications : 1.Atheromas, 2.Abdominal pain, 3.Acute pancreatitis. Risk factors : 1.Low HDL, 2.Increased LDL, 3.DM
|
|
|
3 chemical substances that eleavate TG
|
1. Alcohol, 2.Estrogen, 3.Non-cardioselective B-blockers
|
|
|
3 protective features of the fibrous cap of an atheroma
|
1. Seperates thrombogenic lipid core from plts
2. Seperates the TF found in the lipid core from coagulation factors 3. Structural strength |
|
|
A fibrous cap of an atheroma is vulnerable if (3 causes)
|
1. Thin
2. High ratio of inflammatory cells to SMC 3. Lipid core occupies more than 50% of plaque |
|
|
Biochemical markers of plaque inflammation are ?
|
CRP, serum amyloid A, TNF-alpha, ICAM-1
|
|
|
For the metabolism of homocysteine to Methionin you need which vitamin ? For homocysteine to cystein ?
|
To methionine B12+folic acid, to Cystein B6
|
|
|
Plasma homocysteine levels
|
Moderate elevation 15-40micromol/L, severe elevation >40micromol/L. However studies have shown that risk is increased already at homocystein >12.5micromol/L
|
|
|
Cholesterol levels and CHD, LDL levels and CHD. Also, which cholesterol ratios are important for CHD ?
|
Total cholesterol >6.8mmol/L --> treatment, 5.2-6.8 -->elevated risk
LDL >4.8 --> treatment, >3.8 elevated risk. Ratios used : Totalchol:HDL, LDL:HDL, APOA:APOB(should be high) |
|
|
What is the biochemistry of uric acid in the kidney ?
|
1.Almost totally reabsorbed in the proximal tubules
2. Secreted and reabsorbed in the distal 3. About 10% of filtered load is excreted eventually |
|
|
causes for hyperuricemia
|
1. Essential :
Over production - enzyme defect, underexcretion Secondary : 2. Renal retention 3. Increased turn-over of cells |
|
|
Hyperuricemia levels and risk of gout
|
Males : Above 540micromol/L 90%, 480-530micromol/L 25%
|
|
|
In case of asymptomatic hyperuricemia - what do you check for, and what is the treatment ?
|
Check for urinary uric acid excretion. If >600mg/day give allopurinol (reduce production), if<600mg/day give probenicid to block uric acid renal absorption
|
|
|
3 causes of gout, 4 stages of gout
|
Causes - decreased urate excretion (90%), increased prodcution, secondary gout(alcohol). Stages : 1.Asymptomatic hyperuricemia, 2.Acute gout, 3.Intercritical gout (years), 4.Chronic tophaceous gout
|
|
|
How do you diagnose gout (3 things), 2 thearpy options in gout
|
Dx - Clinical, hyperuricemia demonstration, tophi or crystals in synovial fluid. Tx - Anti-inflammatory drugs, Allopurinol (inhibitor of xanthine oxidase)
|
|
|
What is the criteria for hypouricemia, give 3 causes
|
<0.12mM serum urate
Causes : 1.Severe hepatocellular disease, 2.Defective renal tubular absorption of uric acid 3.Overtreatment with allopurinol |
|
|
What are the two types of MacroCKs', what do you they interfere with ?
|
MacroCK Type I - complex of CK isoenzymes with Ig's (in severe GI and vascular diseases, also cc)
MacroCK II - Oligomeric mitochondrial CK (malignancy, liver disease). They both interfere with immuno-inhibition method of CK-MB determination. |
|
|
Give 4 advantages of CTn. Give 3 FP results with CTn. Which CTn is more sensitive ?
|
1. EArly marker
2. Remains elevated longer than CK-MB 3. Can be used for sizing MI 4. Sensitive. FP : RF, hemolysis, jaundice. CTnI more sensitive. |
|
|
CK-MB - when does it rise, for how long ?
|
Rises after 3-8h, stays for 1-4day
|
|
|
What is the use of Myoglobin as an MI marker
|
It is an early marker, elevated 4-8h after MI -- however it is used only as an exclusion diagnostic (meaning that negative result excludes an MI)
|
|
|
Which MI markers are the more specific ones but are elevated later ?
|
cTnI, cTnT, CK-MB(mass !! not activity !)
|
|
|
What is special about troponins as markers for MI ?
|
As troponins are very sensitive, their level is elevated also in myocardial damage
|
|
|
Which MI marker correlates to size of infarct ?
|
cTn
|
|
|
What are the most widely used vitamin tests ?
|
B1 - Transketolase activity
B2 - Glutation reductase B6 - Aspartate aminotransferase activity C - Leukocyte ascorbate concentration |
|
|
Vit B1 (name, active derivative, function, sources, disease, sx, lab)
|
Thiamine, Derivative - Thiamine Pyrophosphate. Function - Oxidative decarboxylation of pyruvate, transketolase reaction in PPP, nervous functions. Sources - cereals, liver, heart meat. Disease - Beriberi. Sx - Myocardial failure, peripheral neuropathy, psychosis. Lab - RBC transketolase activity
|
|
|
Vit B2 (name, active derivative, function, sources, disease, sx, lab)
|
Riboflavin, Active= FMV/FAD Function - cofactor for oxidation-reduction reactions. Sources- milk, eggs, meat. Sx - glossitis, angular stomatitis, anemia. Lab - RBC glutation reductase
|
|
|
Nicotinic acid - Niacin (function, sources, disease, sx, lab)
|
Function - precursor for NAD,NADP. Sources - endogen from tryptophan, yeasm milk, wheat. Pellagra (dementia, diarrhea,, anemia) Lab : urine metabolites
|
|
|
Vit B6 (name, active derivative, function, sources, disease, sx, lab)
|
Pyridoxine, Functions - AA metabolism, sources - meat, fish, yeast. Hypo - dermatitis, glossitis, vomiting (children). Excess - Peripheral neuropathy, ataxia. Lab - RBC aspartate aminotransferase activity
|
|
|
Vit B12 (name, active derivative, function, sources, disease, sx, lab)
|
Cobalamine. Function - purines, Homocysteine methylation to methionine. Source - only animal products. Transported by IF and TCII. Storage - liver. Lab - Plasma B12 by immunoasy
|
|
|
Folic acid - functions, sources, def, lab
|
Purine,pyrimidine synthesis, synergy with B12 for gene replications. Sources - fruits, vegetables. Def - megaloblastic anemia, Lab - plasma immunoassay
|
|
|
Vit C - function, source, def, lab
|
Reducing agent in hydroxilation reactions, collagen integrity in tissues. Source - citrus fruits, vegetables. Def - scurvy (purpura, poor wound healing, osteoporosis). Lab - leukocyte ascorbate, urine ascorbate after vit c loading
|
|
|
Vit A - name, derivatives, function, source, def, excess
|
Retinol. Derivatives - retinal, retionoic acid. Function - in retinal pigment rhodopsin, epithelial cell growth. Source - synthesized from dietary carotenes. Stored in liver for 10 months. Def - night blindness, keratinization in the skin. Excess (>140microg/ml) : acute - headache, vomiting, skin desqumation. Chronic - anorexia, hepatomegaly
|
|
|
Vit D - function, name, Sourc, def, excess
|
Cholecalciferol (D3), regulatort role in calcium homeostasis. Source - endgenous in the skin by UV light. Dietary (animal fat, fish). Def - rickets/osteomalacia. Excess - hypercalcemia, hypercalciuria
|
|
|
Vit E - name, function, source, def,
|
Tocopheronl, antioxidant, source - vegetable oil, plants. Def - abnormal structure and function of cell organelles --> neurological dysfunction.
|
|
|
Vit K - source, cause of def
|
source - Vegetables, or synthesized in gut by bacteria. Cause of def - fat malabsorption, antibiotics
|
|
|
Name 4 kind of tests in liver diseases. Also - what tests do you use for liver cellular injury
|
1. Tests of cell injury (GOT,GPT,LDH)
2. Tests of liver function (conjugation, synthesis..) 3. Tests of cholestasis (AP, GGT) 4. Tests of etiology(virus, Ab). Liver injury - Mild --> GPT>GOT, Severe GOT>GPT, in both LDH5 increases |
|
|
Name 3 tests of liver function
|
Tests of conjucation and excretion - BSP test
Tests of sythetic functions - clotting tests, other functional tests --> urea cycle (ammonia to urea) |
|
|
What is the BSP test in the liver, what is the procedure, what is the reference range, when is it useful
|
BSP test is a very sensitive and specific test for liver conjugation and excretion function. Procedure - 5mgBSP/Kg I.V., after 45min check for BSP level in blood. Reference - >75% - very severe malfunction, 25-75% severe, 5-25% moderate. Test is useful in cirrhosis, chronic hepatitis
|
|
|
Which clotting parameters would change in conjunction with liver damage ?
|
Moderate liver damage - PT increases. Severe liver damage - PT, APTT, TT increase. In obstructive icterus - PT and APTT increase
|
|
|
Which liver diseases can cause hyperammonia (urea cycle malfunction)
|
Acute - hepatitis, Reye syn
Chronic - cirrhosis |
|
|
What is the ratio of plasma Fe/Cu in hepatic icterus or obstructive icterus ?
|
In hepatic icterus (liver damage) iron is liberated from stores so Fe/Cu increases. In obstruction, copper cannot be excreted with bile so Fe/Cu decreases. Nromal range 0.26-2.6
|
|
|
Name 3 isoenzymes of Alkaline phosphatase, how do you differentiate between them ?
|
1. Tissue nonspecific (liver,bone)
2. Placental 3.Regan (cc). Differentiation is done by exposure to heat or urea which does not inactivate the Regan type (which is, however, inactiated by L-phe) |
|
|
What are the special AP forms found in cholestasis ?
When may GGT be found except for cholestasis ? |
1. High molecular mass AP
2. LpX-ALP complex 3. Intestinal isoenzyme GGT also found in alcoholics |
|
|
What is the LpX, what is it suppose to represent, name 3 components of it, and its positive predictive value
|
Special lipoprotein detected in cholestasis, which composition is similar to bile. It represents bile extravasated to plasma. Contains free cholesterol+phosphatydilcholine mostly. Positive PV is 1
|
|
|
What are the values of gastric acid secretion (basal, stimulated, male/female). In testing for achlorydia, when will you have no response to pentagastrin ?
|
Basal - male <10mmol/h, female <6.
Stimulated - <45mmol/h, female <35. No response to pentagastrin in atrophic gastritis, gastric cc) |
|
|
How do you detect Z-E ? What are 2 consequences of ZE ?
|
1. High serum gastrin.
2. Secretin provocation causes increase of gastrin only from gastrinomas. Consequneces - 1.bile acids are insolulble due to low pH 2. B12 is not absorbed |
|
|
Give 3 tests for the presence of H.Pylori, what is the sensitivty/specificty of the 13C-urea breath test ? Also, what is measured in the breath test, and by which method ?
|
Test :
1.Serology 2. Culture 3. Breath test. The sensitivity of the 13c breath test is 98% (!!) and the specificity is 100(!!). 14Co2/13Co2/12Co2 is measured by Gas-chromotography |
|
|
Give 3 usese for breath-tests used, and also 3 isotopes used ?
|
Tests - H.pylori, Glucose for CH metabolism, Lactose. Isotopes - C13, N15, O18
|
|
|
Give 3 tests for Celiac disease
|
1. Anti-Giladin Ab - ELISA
2. Anti-transglutaminase Ab - ELISA 3. Gut biopsy |
|
|
Give 3 tests used in the general diagnostics of intestinal disorders
|
1. Xilose absorption test (CH absorption in jejunum)
2. Fecal AA measurement (AA absorption) 3. Triolene breath test (Fat absorption) |
|
|
Give 3 causes and 3 clinical features of acute pancreatitis
|
Causes :
1. Alcohol 2. Cholelithiasis 3. Mumps, infections Clinical features : 1. Acute abdomen 2. Pain referred to back 3. Hypotension/circulatory shock |
|
|
Give 4 tests of acute pancreatitis
|
1. Serum alpha amylase
2. Urine amylase 3. Serum lipase 4. Immunoreactive trypsin |
|
|
Give 2 causes for markedly increased serum amylase (>5X) and 2 causes for moderately increased (<5x)
|
Markedly increased :
Acute pancreatitis Perforated peptic ulcer Tumors of lung Moderately increased : Peritonitis Acute alcoholic intoxication Macroamylasemia |
|
|
What is the reference interval of the Amylase/creatinine clearance ratio, what happens to it in Acute pancreatitis ?
|
Ref 2-5%, increased in acute pacnreatitis
|
|
|
Where is lipase produced, what is its function, and does it occur in the urine ?
|
Produced ONLY in pancreas, hydrolizes emulsified Tg. It does not appear in urine, totally reabsorbed.
|
|
|
What is the time course of Se/U amylase, of Se lipase (rise, return to normal). Also, what is the sensitivity of alpha-amylase test, and of amylase+lipase
|
Se amlyase - rise 2-12h, normal at 3-4d
U amylase - rise 2-12h, normal 5-7d Se Lipase - rise 4-8h, normal 7-14d (!!). Sensitivity of amylase - 80%, of amylase+lipase 94% (!!) |
|
|
What are the diagnostic tests used for GH ? Also, which hormones are mostly affected in Hypopituitarism ?
|
GH - Suppression by OGTT, stimulation by insulin
Mostly affected are GH, then LH/FSH, then ACTH (usually in combination) |
|
|
A functioning adenoma in the pituitary would cause mostly which hormones to be elevated ?
|
Hyperpituitarism due to functioning tumor --> mostly PL, then GH, Then ACTH
|
|
|
DD of cushing (which types, which one
|
Adrenal hyperplasia, adrenal adenoma , adrenal CC, pituitary tumor, ectopic ACTH. In ectopic ACTH and pituitary tumor ACTH is high, all others ACTH is low.
|
|
|
What are the two types of diabetes insipidus. What is the process of the fluid deprivation test and how can it differentiate between the 2 types ?
|
Types - Nephrogenic diabetes insipidus (kidney does not respond to ADH), cranial (post pituitary does not produce ADH). In the test the patient is deprived of fluids for 8h, and then is allowed to drink and given vasopressin nasaly, and osmolality is measured every 4 hours. In nephrogenic, there will be no response to the vasopressin
|
|
|
Give 3 indications for thyroid function tests other than in suspicion if hypo/hyper thyroid. When do you have high TSH other than hypothyroid ? When do you have low TSH other than hyperthyroid ?
|
1. Newborns
2. Elderly 3. Post partum High TSH - Recovery from severe illness, low TSH - severe illness (acute phase) |
|
|
What are the stages of the sick euthyroid syndrome ?
|
Acute phase of a non-thyroidal illness : fT3 decreases, rT3 increases. Recovery phase - ft3/ft4 return to normal, TSH increased.
|
|
|
How do you screen for congenital hypothyroid ? Give 3 causes of secondary hyperthyroid
|
serum TSH from capillary blood 6-8days after delivery.
Secondary hyperthyroid - Graves, neonatal hyperthyroid (maternal TSI), trophoblastic tumors (hCG is stimulatory) |
|
|
What is the general rule for diagnosis of hyperthyroid ? Which Ab are present in graves, in hashimoto ?
|
TSH decreased, < 0.1mU/L (fT3,fT4 increased).
In graves - TSI, in hashimoto - Anti-TG, Anti-TPO(Anti microsome) |
|
|
Give 3 clinical features of hypercalcemia
|
1. Renal failure
2. Decrease neuromascular excitablity 3. Cardiac effects --> >3.75mmol/L Cardiac arrest |
|
|
Give 4 causes of hypercalcemia
|
1. Increased protein-bound Ca in dehydration
2. Increaed PTH 3. Vit D excess 4. Sarcoidosis 5. PTHrP, bone metastasis(osteoclastic) |
|
|
What is the milk-alkali syndrome, what is familial hypocalcuric hypercalcemia ?
|
Milk alkali - ingetsion of antacids for dyspepsia causes decreased renal excretion of calcium --> hypercalcemia. Familial hypocalcuric hypercalcemia - AD, PTH setpoint is changed
|
|
|
Give 3 causes of hypocalcemia. Give 4 tests in disorders of calcium.
|
1. Decreased protein-bound Ca due to hypoalbuminemia,
2. Decreaed PTH 3. Vit D def. Tests: 1. Serum total Ca with albumin 2. Serum Ca2 level 3. Serum PTH 4. Urinary calcium/phosphate |
|
|
Give 3 tests for the function of the adrenals, also, how is cortison transported in blood
|
3 tests of adrenal : 1. Plasma cortisol, 2.Urinary cotrisol, 3.ACTH.
Cortisol in plasma is 95% bound to transcortin or albumin |
|
|
Give 3 functions of cortisol, give 3 clinical features of cushing
|
Functions of cortisol : 1.Increase protein catabolism, 2.Increase hepatic glucogenolysis, 3.Increase hepatic gluconeogenesis.
Clinical features of cushing : 1.Moon face, 2.Purple striae, 3.Hypertension, 4. Glucose intolerance |
|
|
3 tests of cushing ?
|
1. 24h urinary cortisol
2. Dexamethasone suppression test 3. Night sample - cessation of diurnal variation |
|
|
2 causes and 3 symptoms of Addison ?
|
Causes : 1. AIDS, 2.Autoimmune adrenalitis
Symptoms : 1.Fatigue, 2.Weight loss, 3.Hypotension |
|
|
What is the lab diagnosis of Addisson (ranges) ? What is the Synachten test ?
|
Dx : 1.Serum Na down, K up, 2.Cortisol <50nmol/L --> diagnostc, >550nmol/L --> excluded, 50-500nmol/L --> Synacthen test. Synacthen : measure cortisol before 250microg synacthen, and after. Cortisol levels should rise.
|
|
|
Give 2 causes for primary hyperaldosteronism, and 2 for secondary (increased renin !)
|
Primary - Conn, adrenal adenoma. Secondary - hypoalbuminemia, cardiac failure
|
|
|
Mention 2 congenital adrenal hyperplasias. What are the their symptoms
|
21-Hydroxylase def : block causing no coritsol or aldosteron --> increased androgens. Females : ambigous genitalia, infertility, hirsutism. Males - precocius puberty.
11beta-hydroxilase def : increased androgens, hypertension due to salt retaining properties of the 11-deoxycorticosterone precursor. |
|
|
What is the dx of CAH
|
21-hydroxylase def : increased serum 17-OHP
11beta-hydroxylase def - increased serum 11-deoxycortisol |
|
|
Catecholamine synthesis chain, also which step takes place in the mitochondria
|
Tyrosin-->DOPA-->Dopamine-->Norepi-->Epi. Tyrosine to DOPA takes place in mitochondrium
|
|
|
Name 2 diseases associated with increased catecholamine metabolism from chromaffin chells, and two from neural cells
|
From chromaffin - Phaeochromocytoma, Paraganglioma. From neural cells - Neuroblastoma, Ganglioneuroma
|
|
|
Name 3 occurences of familial pheochromocytoma, and 3 clinical symptoms of pheochromo
|
Occurences : 1. With MEN2a,2b. 2. With NF (Vol Ricklinghausen), 3.With VHL.
Symptoms : 1.Hypertension, 2.Sweating, 3.Loss of weight |
|
|
What are the preparation steps needed for catecholamines determination ?
|
Preparation : 1.Avoid drugs interefering with catecholamines for 8 days prior. 2. Avoid certain foods for 3 days prior.
3. To check plasma level : 30min in supine pos, canule 20-30min in advance, draw blood at same time of day, not after food. 4. To check urine : 24h collection, avoid heavy exercise |
|
|
Drugs interfering with catecholamine determination, also - dx of pheochromocytoma
|
Drugs - 1. Drugs interfering with HPLC assay - MethylDOPA, 2.Drugs inhibiting catecholamine production/release : MAO inhibitors, reserpine. 3. Drugs increasing their excretion : 1.Caffeine, 2.Glucagon.
Dx of pheochromo : 1.Clinical 2.Urine : metanephrines (96% sensitive !!), VMA, catecholamines 3.Plasma : catecholamines, provocation test, imaging (CT,MRI) |
|
|
3 conditions in which plasma catecholamines may be raised
|
1. DKA
2. AMI 3. Hypoglycemia, stress, etc |
|
|
What is neuroblastoma, is it common, is hypertension present ?, what is its dx, what is the sensitivity of single assays and of combined ones ?
|
Neuroblastoma - from neuroblasts of adrenal medulla and sympathetic trunk. 3rd most common malignant tumor in children !, Hypertension usually absent !
Dx : 1. Norepi, Dopamine, VMA, HVA increased in urine (NOT EPI !). Single assays have 75% sens, combined ones have 95% ! NSE may increase (neuron specific enolase) |
|
|
Which cells does FSH work on in the testis ?, what do sertoli cells produce ?
|
FSH works on both leydig and sertoli cells. Sertoli cells produce inhibin
|
|
|
What are the major androgens, how are they carried in plasma
|
Androgens : Testosterone (in testins) --> DHT (periphery), Androstendione (testis+adrenals), Dehydro-epiandrosteerone (both again).
In plasma : 2-3 unbound, active, 97% bound to Albumin and SHBG |
|
|
What is the problem in male infertility if LH is up, testosterone is down. If FSH up, sperms down ?
Which other tests can you perform to diagnose male infertility ? |
1. LH up, test down -> leyding cell dysfunction
2. FSH up, sperms down -> seminefrous tubules failure. Other tests : 1.semen analysis 2.Chromosome analysis 3.Immunological tests |
|
|
FSH,LH --> their Alpha subunit is identical with which other hormones ?
|
1. FSH,LH,hCG,TSH all have same alpha units, Beta is unique.
|
|
|
How many carbons are there in Estrogens, progesterones, androgens. Also, how is progesterone carried in plasma ?
|
Estrogens - 18C, Androgens-19C, Progesterones- 21C. Progesterone in plasma : 2-10% unbound, active. 90-98% bound to CBG (high affinity)
|
|
|
How are estrogens carried in plasma ?, SHBG - for which hormones does it have a higher affinity, what does a decrease in SHBG cause, what does an increase in sHBG cause ?
|
Estrogens : 2-3% unbound, active. 97% bound to albumin and SHBG(high affinity).
SHBG has a higher affinity to estrogens than to testosterone. Decrease of SHBG causes increase in testo more than estro --> androgenic effect. The opposite happens with an increase in SHBG -->anti-androgenic effect |
|
|
What is the difference between primary amenorrhea and secondary. Also name 3 causes of primary amenorrhea
|
Primary - mensturation has never occured until age 16. Causes : Hypothalamic (decreased GnRH), Hypophysis - Hypopituitarism, Gonads - Turner. Secondary ammenorhea - absence of at least 6 months in women who've had normal cycles
|
|
|
Give 2 causes, 3 sx, and dx of Prolactinaemia
|
Causes : 1.Microadenoma compresses blood supply, reduces DA, 2.Ectopic secretion. Sx - Galactorrhea, Amenorrhea. Dx - PRL determination, TRH stimulation
|
|
|
What is the dx of POCS ?
|
Testosterone, estrogen increased, FSH down, LH up
|
|
|
Give 4 tests done in Amenorrhea
|
1. Exclude pregnancy
2. LH,FSH,Estradiol 3.Prolactin, 4.ACTH |
|
|
What is the sequence of events in dynamic functional tests for amenorrhea. How do you examine the hypothalamus-pituitary axis
|
1.Progesterone (examine uterine function) if no bleeding --> Estrogen+progesterone, if no bleeding -->disease of uterus.
Hypothalamus-pituitary : give clomiphene citrate which blocks the inhibitory effects of steroids on GnRH, therefore induce GnRH-->should cause FSH,LH up |
|
|
Dx of hirsutism and virilism, give 4 tests
|
1. Testosterone level
2. SHBG 3. FSH,LH (High LH -->POCS?) 4. 17-OHP (CAH) |
|
|
What is the difference between sterility and infertility. Give 4 dx of female infertility
|
Sterility - no pregnancy within 2 years. Infertility - pregnancies end up with spontanoues abortions. Dx - Hormones, sperm examination, postcoital test, examination of cervical mucous
|
|
|
Give 3 ways to test for ovulation ?, also give 3 contraindications for oral contraceptives and 2 side effects.
|
1. Progesterone peak 5-9 post ovulation
2. Basal body temp rises 0.5C after ovulation (morning?) 3.LH surge 24-36h before ovulation. Contraindications : 1.Renal disorders, 2.history of thrombosis, 3.cardiovascular diseases. Side effects : 1.Post pill amenorrhea, thrombosis/emboli |
|
|
Give 4 secondary metabolic changes occuring in pregnancy. Also give 3 markers of bone formation
|
1. Albumin down
2. AP up 3. Glucose tolerance down 4. Thyroxin up Markers of bone formation : 1.Osteocalcin 2.Bone specific alkaline phosphataase BSAP 3. Pro-collagen I extension peptides (PICP, PINP) |
|
|
3 features of OSteocalcin (BGP)
|
1. Produed by osteoblasts, stimulated by VitD
2. undergoes posttranslational carboxylation (Vit K!) and binds Ca 3.Chemotactic for osteoclasts |
|
|
What are the advantages of AP over Ostecalcin as a marker of osteblastic activity ? Also, what is the problem with PICP, PINP as markers of osteoblastc activity ?
|
1. Longer half life (1-2d)
2. No proteolysis in serum 3.No effect of renal function on its serum cc. Procollagen peptides are non-specific and non-sensitive as collagen is formed in other tissues as well |
|
|
Give 4 markers for bone resorption
|
1. Calcium clearance
2. Hydroxyproline clearance 3. C and N telopeptide crosslaps (CTX,NTX) 4. TRAP |
|
|
2 X-ray findings and 3 lab findings in Paget's disease
|
X-ray : 1.Increased bone density, 2.Abnormal architecture
LAb : 1.Se BSAP increased, 2.Urine pyridinoline crosslaps clearance increased 3.Serum Ca2+, Phosphate normal |
|
|
Give 3 causes for Rickets-osteomalacia. Also 2 x-ray findings, and 2 lab findings.
|
1. Vit D def
2. 1alpha-hydroxylase def 3.Vit D receptor defect. X-ray : bowing long bones, def. minerlization of bone matrix Lab : 1.Serum BSAP up, Serum P down (PTH!) |
|
|
4 lab findings in Renal osteodystrophy
|
Serum phosphate up, serum BSAP up, se creatinine up, se Active vitaminD down
|
|
|
Give 4 risk factors for osteoporosis, also give 3 secondary osteoporosis
|
1. Estrogen def
2. Cushing 3. Alcoholism 4. RA 5. Low calcium diet. secondary : 1.Hyperthyroid, 2.MM, 3.Chronic liver diseases |
|
|
What is the inducer, what is the duration, and what is the defective gene in Periodic Paralysis
|
Hypokalemic- Inducer is glucose, duration few hours, chr 1,AD.
Hyperkalemic - Inducer KCl or exercise, 30-40duration, chr 17,AD |
|
|
What is the gene defect, what is the trigger,and 3 lab findings in malignant hyperthermia
|
AD, Chr 19, Ryanodine Rec.
Trigger is inhalation or local anasthetics. Lab : pH<7.2, Increaed lactic acid, Extremely high CK |
|
|
Muscular dystrophies - frequency, function of dystrophin, size of gene, main symptoms of DMD,BMD, inheritence
|
One of the most common inherited diseases, dystophin has a critical role in maintanance of the complex that binds actin to the sarcolemma. Largest gene in genome (2300kb). DMD -> wheelchair by 12, mental retard. BMD -> milder, no wheelchair, no mental. X-linked.
|
|
|
3 methods to detect DMD,BMD. How do you screen for deletions in DMD/BMD,
|
1. CK elevated 50x-100x
2.Immunoblotting - no protein in DMD, altered in BMD. Deletion screening - Multiplex PCR |
|
|
How do you detect duplications and point mutations in DMD/BMD ? How is MLPA different from PCR ?
|
MLPA. Different from PCR in that the probes are amplified instead of the genomic DNA.
|
|
|
What are LGMD ?
|
Limb-Girdle MD, inherited as AD, AR. Very hetergenous, CK elevated 10x-120x, in most cases alpha-Sarcoglycan deficient.
|
