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279 Cards in this Set

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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
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
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
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
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
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
2. Plt count
3. Tests indicating activation of coagulation and fibrinolysis --> D-Dimer
4. Tests indicating consumption of inhibitor --> AT-III
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-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
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
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
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
III - IDL or beta-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 ?
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 :
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 :
Acute alcoholic intoxication
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.
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 :
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
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
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 :
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)
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.