Arab Board Clinical Pathology Part 1 cheat sheet
Arab Board Clinical Pathology Part 1 · Keep the key ideas within reach.
General Pathology and Pathophysiology
Necrosis types: coagulative (ischemia, preserved architecture), liquefactive (brain, abscess), caseous (TB), fat (pancreas, saponification), fibrinoid (vasculitis, immune injury).
Apoptosis is energy-dependent, caspase-mediated, non-inflammatory; necrosis is passive, membrane-rupturing, and provokes inflammation.
Acute inflammation: vasodilation, increased permeability, neutrophil emigration via margination-rolling (selectins)-adhesion (integrins)-transmigration-diapedesis-chemotaxis.
Granuloma = collection of activated macrophages (epithelioid cells), often with Langhans giant cells; seen in TB, sarcoidosis, foreign body, leprosy, fungal infection.
Wound healing: primary intention has apposed edges and little granulation; secondary intention has tissue loss, more granulation, wound contraction, and scarring.
Cell injury is reversible until mitochondrial ATP depletion and membrane integrity loss become irreversible; key markers are mitochondrial swelling and membrane rupture.
Metaplasia (e.g., squamous metaplasia of bronchial epithelium in smokers) is an adaptive change that can predispose to dysplasia and carcinoma.
Amyloid is a misfolded beta-pleated-sheet protein (Congo red positive with apple-green birefringence under polarized light); AA (serum amyloid A) vs AL (immunoglobulin light chain).
Clinical Chemistry
Anion gap = Na - (Cl + HCO3); reference about 8-12 mmol/L; elevated gap suggests unmeasured anions (lactate, ketones, methanol, ethylene glycol, salicylate, uremia).
Osmolal gap = measured osmolality - calculated osmolality (2Na + glucose/18 + urea/2.8); gap >10 suggests toxic alcohols.
Henderson-Hasselbalch: pH = 6.1 + log(HCO3 / 0.03 x pCO2); Winter formula: expected pCO2 = 1.5 x HCO3 + 8 (+/-2) for metabolic acidosis.
Corrected calcium (mg/dL) = measured Ca + 0.8 x (4.0 - albumin g/dL); ionized calcium is the physiologically active fraction.
Troponin I and T are highly cardiac-specific; CK-MB is less specific (skeletal muscle); myoglobin rises earliest but is nonspecific.
LDL cholesterol (Friedewald) = total cholesterol - HDL - triglycerides/5, valid when triglycerides <400 mg/dL.
eGFR by CKD-EPI uses creatinine, age, and sex; creatinine is affected by muscle mass, so low-muscle patients may have misleadingly normal values.
HbA1c reflects average glycemia over about 2-3 months (RBC lifespan); values may be falsely low with hemolysis or hemoglobin variants.
Hematology and Coagulation
MCV = (Hct x 10)/RBC (fL); MCH = Hb/RBC (pg); MCHC = Hb x 100/Hct (g/dL); RDW reflects anisocytosis.
Iron deficiency: low ferritin, low serum iron, high TIBC, low transferrin saturation, high RDW, microcytic hypochromic; anemia of chronic disease: low iron, low TIBC, high ferritin.
Intravascular hemolysis markers: elevated LDH, elevated indirect bilirubin, low haptoglobin, hemoglobinuria, and schistocytes on smear.
PT/INR evaluates the extrinsic and common pathway (factors VII, X, V, II, fibrinogen); aPTT evaluates the intrinsic and common pathway (VIII, IX, XI, XII, X, V, II, fibrinogen).
Heparin therapy is monitored by aPTT (or anti-Xa); warfarin is monitored by INR; a prolonged aPTT that corrects with mixing study suggests factor deficiency, not inhibitor.
DIC: prolonged PT and aPTT, low fibrinogen, elevated D-dimer and fibrin degradation products, thrombocytopenia, schistocytes.
CML is characterized by t(9;22) BCR-ABL1; APL (M3) by t(15;17) PML-RARA; Burkitt lymphoma by t(8;14) MYC-IgH.
Sickle cell disease: HbS polymerizes on deoxygenation, causing vaso-occlusion and hemolysis; confirm by hemoglobin electrophoresis or HPLC.
Medical Microbiology and Infectious Disease Serology
Gram stain: Gram-positive retain crystal violet-iodine (thick peptidoglycan, purple); Gram-negative decolorize and take safranin (pink).
Catalase-positive, coagulase-positive gram-positive cocci in clusters = Staphylococcus aureus; coagulase-negative = Staphylococcus epidermidis.
HBsAg indicates current HBV infection; anti-HBs indicates immunity; anti-HBc IgM indicates acute or recent infection; HBeAg indicates high infectivity.
HIV screening uses fourth-generation combined antigen/antibody assays (detects p24 and anti-HIV); confirmation by Western blot or nucleic acid testing.
Syphilis serology: nontreponemal tests (RPR, VDRL) are used for screening and monitoring; treponemal tests (TPPA, FTA-ABS, EIA) confirm.
Epstein-Barr virus: heterophile antibody (Monospot) may be negative in young children; VCA-IgM indicates acute infection, EBNA indicates past infection.
Blood culture sets should be drawn before antibiotics, with at least two sets from separate sites; incubation is typically 5 days for routine organisms.
MRSA is detected by cefoxitin/oxacillin disk or mecA/PBP2a testing; ESBL producers are resistant to most penicillins and cephalosporins but susceptible to carbapenems.
Clinical Immunology and Immunopathology
Type I hypersensitivity is IgE-mediated (mast cells, basophils); Type II is antibody-mediated against fixed antigens; Type III is immune-complex mediated; Type IV is T-cell mediated (delayed).
ANA is a sensitive but nonspecific screening test for SLE; anti-dsDNA and anti-Sm are highly specific, and anti-dsDNA correlates with disease activity and nephritis.
Anti-CCP is highly specific for rheumatoid arthritis; rheumatoid factor is sensitive but not specific.
Complement: low C3 and C4 with normal total hemolytic complement suggests consumption; C3 nephritic factor causes low C3 with normal C4.
Primary immunodeficiency: Bruton X-linked agammaglobulinemia (no B cells, low all immunoglobulins); DiGeorge syndrome (T-cell defect, hypocalcemia, cardiac defects).
Flow cytometry immunophenotyping uses CD markers: CD4 helper T cells, CD8 cytotoxic T cells, CD19 B cells, CD3 pan-T, CD56 NK cells.
Allergic contact dermatitis and tuberculin skin testing are Type IV delayed hypersensitivity reactions, read at 48-72 hours.
Celiac disease: anti-tissue transglutaminase IgA and anti-endomysial IgA are first-line; total IgA must be checked for IgA deficiency.
Laboratory Genetics and Molecular Diagnostics
PCR: denaturation (about 94-95 C), annealing (about 50-65 C), extension (about 72 C); each cycle doubles the target.
Real-time PCR quantifies product by fluorescence (SYBR green or probes such as TaqMan); Ct value is inversely related to starting template amount.
Karyotyping detects balanced translocations and aneuploidy; FISH detects specific loci or deletions; microarray detects copy-number variants but not balanced rearrangements.
Sanger sequencing is the reference method for single-nucleotide variants; next-generation sequencing enables massively parallel sequencing of many genes.
Inheritance: autosomal dominant (50% recurrence, vertical transmission); autosomal recessive (25% recurrence, consanguinity); X-linked recessive (affected males, carrier females).
Trisomy 21 (Down syndrome) risk rises with maternal age; prenatal screening includes combined first-trimester screen and cell-free DNA.
BRCA1/BRCA2 pathogenic variants confer high lifetime breast and ovarian cancer risk and follow autosomal dominant inheritance.
Molecular testing requires contamination control: separate pre- and post-amplification areas, negative controls, and UNG or similar carryover prevention.
Transfusion Medicine and Blood Banking
ABO compatibility: group O is universal donor for RBCs; group AB is universal recipient for RBCs; group AB plasma is universal donor plasma.
Crossmatch: immediate spin (ABO), anti-human globulin phase (IgG and complement), and computer/electronic crossmatch for patients with no history of antibodies.
RhD-negative recipients should receive RhD-negative RBCs; RhIG is given to RhD-negative mothers to prevent anti-D alloimmunization.
Delayed hemolytic transfusion reaction: fall in hemoglobin, positive direct antiglobulin test, and new alloantibody 5-10 days after transfusion.
Febrile non-hemolytic reaction is the most common transfusion reaction; acute hemolytic reaction (ABO mismatch) presents with fever, chills, flank pain, and hemoglobinuria.
TRALI presents with acute hypoxemia and bilateral pulmonary infiltrates within 6 hours of transfusion; TRALI is often associated with donor anti-HLA or anti-neutrophil antibodies.
Platelet storage: 20-24 C with agitation; RBC storage: 1-6 C; fresh frozen plasma stored at or below -18 C and used within 24 hours after thawing.
Blood components: leukoreduction reduces febrile reactions and CMV transmission; irradiated components prevent transfusion-associated graft-versus-host disease.
Laboratory Management
Quality management system components: organization, personnel, equipment, purchasing, process control, documents, occurrence management, assessment, and continuous improvement.
Cost analysis: fixed costs are independent of test volume; variable costs change with volume; total cost per test falls as volume increases because fixed cost is spread.
Turnaround time (TAT) = from specimen collection or receipt to result reporting; monitor with percentiles (e.g., 90th percentile) rather than means.
Staffing and workload: use workload units (e.g., CAP workload units) to estimate staffing needs; skill mix and competency assessment are required for accreditation.
Inventory control: par levels, first-in-first-out rotation, and reorder points based on lead time and usage reduce stockouts and wastage.
Accreditation standards (ISO 15189, CAP) require documented training, competency assessment, and periodic review of procedures and quality indicators.
Risk management: failure mode and effects analysis (FMEA) proactively identifies failure modes; root cause analysis investigates adverse events.
Key performance indicators include specimen rejection rate, critical value reporting, turnaround time, and corrected report rate.
Quality Assurance and Laboratory Safety
Levey-Jennings chart: plot control values over time with mean and standard deviation lines; Westgard rules flag systematic or random error.
Westgard 1-2s rule is a warning; 1-3s, 2-2s, R-4s, 4-1s, and 10x rules indicate rejection or investigate the run.
External quality assessment (proficiency testing) compares results across laboratories; unacceptable results require investigation and corrective action.
Biological safety levels: BSL-1 (minimal), BSL-2 (most clinical labs), BSL-3 (serious aerosol risk), BSL-4 (dangerous, exotic agents).
Standard precautions apply to all patients: hand hygiene, gloves, gowns, eye protection, and safe sharps handling; transmission-based precautions add contact, droplet, or airborne measures.
Chemical hazards: review safety data sheets (SDS), use fume hoods for volatile reagents, and follow spill and waste disposal procedures.
Sharps injury: wash the site with soap and water, report immediately, and follow post-exposure prophylaxis protocol for HIV, HBV, and HCV.
Fire safety uses the RACE sequence (rescue, alarm, confine, extinguish/evacuate); know the location of extinguishers and emergency exits.
Laboratory Instrumentation
Spectrophotometry uses Beer-Lambert law: absorbance = molar absorptivity x path length x concentration; measure at the wavelength of maximum absorbance.
Photometry requires a stable light source, monochromator or filter, cuvette, and detector; stray light and cuvette quality affect linearity.
Ion-selective electrodes measure activity of ions (Na, K, Cl, Ca); direct ISE is unaffected by protein, indirect ISE can be affected by hyperproteinemia or hyperlipidemia.
Centrifuges: relative centrifugal force (RCF) = 1.118 x 10^-5 x r (cm) x rpm^2; balance tubes and follow rotor limits.
Automated analyzers: continuous flow, centrifugal, and discrete random-access systems; discrete analyzers are most common in clinical chemistry.
Hematology analyzers use electrical impedance (Coulter principle) and/or flow cytometry with light scatter for cell counting and differentials.
Chromatography separates by differential partitioning between mobile and stationary phases; HPLC is used for HbA1c, drugs, and hemoglobin variants.
Mass spectrometry (LC-MS/MS) offers high specificity and sensitivity; it is used for therapeutic drug monitoring, steroids, and newborn screening.
Methodology and Statistics
Sensitivity = TP/(TP+FN); specificity = TN/(TN+FP); positive predictive value depends on prevalence, negative predictive value also depends on prevalence.
Accuracy is closeness to the true value; precision is reproducibility; bias is systematic error; random error affects precision.
Coefficient of variation (CV) = (SD/mean) x 100; used to express imprecision of a method.
Reference interval: typically mean +/- 2 SD covers about 95% of a healthy population; 90% confidence interval for limits uses nonparametric percentile methods.
Correlation coefficient r measures linear association; r^2 indicates the proportion of variance explained; correlation does not prove agreement.
Bland-Altman plot compares two methods by plotting the difference against the mean; limits of agreement are mean difference +/- 1.96 SD.
t-test compares means of two groups; ANOVA compares means across three or more groups; chi-square tests association for categorical data.
Sample size and power: power increases with larger sample size and larger effect size; type I error (alpha) is a false positive, type II error (beta) is a false negative.