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Integrated Pathology Notes PDF

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54 views69 pages

Integrated Pathology Notes PDF

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"Note: This materials copyrighted. AI rights reserved. Raward Goljan, 1, 2003, INTEGRATED PATHOLOGY NOTES © “The following arc high yield facts that are meant to complement the notes. Some of the items cover ‘concepts that are taught by other aches inthe eouse tat dretly slate to palblogy. Oth items cover topes hat donot have time o tach ding the review (envionment patbelogy, mation, ed yield subjects that Tse on exams and. ‘guizes for my’ own students that will provide you with additional questions to quality control what you have learned. ‘Terms for lab test results: true positive (KP) positive tes xesult in ayuteat with he disease, © {alse negative (FN)— negative (normal) tet result in a patient with the disease, « true negative (CIN}- negative (normal) test result in a patent without the disease, «false positive (FP) positive test resull in a patient without the disease, « egutive predictive value of a test result (PV) chance tht a negative (normal) tes eeu isa TN rater than a FN, positive predictive value of a test result (PV")- chance that a positive test result iso TP rather than a FP Sensitivity of n test: 1. "positivity in disease"~ formula for sensitivity: TP /‘TP + FN 2. use ofa test with 100 4% sensitvty- « best used to sxeen fr disease excludes disease when the test result retums negative, «includes people with disease when the tit result returns postive, buzz words: exchides and includes 3. negative predictive value (PY-) of a test with 100% sensitivity » PY" nnust be 100% since there are no FN test results in a test with 100% sensitivity~ this underseaxes why test with 100% sensitivity exclude disease when the test result retums negative, * e.g, serom 140 mp/dL. to >126 mg/dL) ‘on sensitivity, specificity, PV’, and PV: 1. increases sensitivity and negative predictive value (PV) — A. dropping the upper limit to lower value means that more people with a negative test result are likely to be TNs (not have DIM) rather than FIs 1B, sensitivity and PV” always inerease when the upper limitof a testis lowered 2. detreases specificity and positive predictive value (PV")- ‘A. fewer people are tikely to have: DM, atest result >126 mg/dl is more likely o be @ FP ‘than a TP test result B. summary schematic Normal Disease v4 0 — Interval 0-4 ‘Seostivity 100% (no FNS) PY 100% Specificity decreases PV decreases ——> Interval ~10 Specificity 100% (no FP) FV" 100% Sensitivity decreases PV decreases © Prevalence: 1, Rrevalence (aumber of people with disease in the population studied) ~ Incidence (aumber of new cases over 2 period of time) x Duration ofthe disease A P=Ixd B. as duration (D) decreases, prevalence (R) decreases ©. asD increases, P increases 1D. _imeidence (1) isa constant fn this relaiionship E, _ PV+ increases when prevalenoe increases: more TPs F._PY-increnses when prevalence decreases; more TNs 2, prevalence calculation— TP + FN (all people with diseasey TP + FN 4 TN + FP (all people ‘with and without disease) 3. example— if treatment for lenkemia lengthens the survival period but docs not lead to its cure, prevalence (P) of leukemia increases owing to the incresse in duration (D): no effect on incidence (number of new eases of lelkemia) "Note: This material i copyrighted. All rights reserved. Rdward Goljan, M.D. 2003 ‘© Example of « caleulation for sensitivity, specificity, PV+, PV-, and prevalence: Disease No Disease Positiveest (ER) 60 R) 40 Negative test (EN) 20 (IN) 80 Sensitivity ofthe test: TP TP + FN'= 60 /80 ~ 75% Specificity ofthe test: TN/'TN + FP = 80/120 = 66% PV: TN/TN++FN = 80/ 100 = 80% (80% chance it is a'TN and a 20% chance itis a FN) PV: TR/TP + EP = 60 / 100 = 60% (60% chance it is a TP and 40% chance it is a KP) ‘Prevalence: TP -+FN/'TP-+FN+TN+FP = 80 /200= 4076 Rar cigs peony: ‘greater increase in plasma volume than RBC mass— ‘A. decreases hemoglobin (Hb) and heratogrit (fe); lutional effect B. increases glomerular filvation rate (GFR) and creatinine clearance (CCH): due to {increased plasma volume decreases serum BUN/creatinine/uric acid: dilutional effect + increased vlearance 2. Increased alkaline phosphatase~ placental crigin 3. respiratory alkalosis— estrogen/progesterone effect on CNS respiratory center causing increased clearance of COs per breath 4. increased T, and cortisol A. increased synthesis of thelr respective binding protelus B. free hormone levels are normal ©. no signs of fyperthyroidism/hypercortsolism D. eg, normal serum TSH and ACTH, respectively ‘= Newborn: high hemoglobin (Ht) due to ineresse in T6F— 1. left shifts oxygen dissociation curve (ODC): causes tise hypoxia-> 2, slimulus for erythropoictin (EPO) release» 3, imereases RBC production with subsequent increase fa Hb concentration = Children: 41, Imereased serum alkaline phosphatase (ALP)~ A. 3-5 times higher than adults B. osteoblasts release enzyme when stimulated by vitamin D ©. ALP increases bone mineralization 2. increased serum phosphate required to drive caleium into bore ‘4. _slight decrease in hemoglobin concentration when compared to adult levels ‘& Main laboratory difference in adalt male and female: 1. fron studies are all lower in women- eg, seruin iroa and feritin 2. lower Hb concentration in women Changes in old age: 1, renal changes~ deerease in GFR and CCr 2. slight merease in alkaline phosphatase~ due to reactive bone formation in osteoarthritis 3. slight decrease in Hgb concentration in males~ duc to decrease in androgens (normal ‘values are those of a female) © Analytes increased with hemolyzed blood sample secondary to venipuncture: 1 ED A. DIY isvenzyme fiuction is primarily increased and is greater than LDH isoenzyme faction (LDAVLDH, fip) ‘Note: This material is copyrighted. Al rights reserved. Edward Galfan, M.D. 2003 1B, false positive acute myocardial infarction C. LE, isoenzyme is also n cardiac muscle LDH, LDH; LDH, LDH, LDH, eae | | a rt perce hes Acute myocardial infaretion: LDEL/LDT, flip 1B. Kis the major intracellular cation C, _ECG will not show a peaked T wave 7 Lp most ateted by tasting: £ triacylglycerol (TG) component coming from chylomierons~ chylomicrons contain diet- derived 1G fasting or lack of fasting does not affect cholesterol (CH) and high-density lipoprotein (GIDL) concentration A. nommally, CH is <3% ofthe ehylomieron fraction 'B. fasting is unnecessary for an accurate CH or HDL-CH fasting is necessary for an accurate caleulated low-density lipoprotein (LDL)~ A. LDL=CH-HDL-TGis (VLDL fraction) B. if TG is falsely increased by chylomicrons fiom the dic, it will falsely lower the ealcuisted LDL and falsely increase VLDL (16/5) ‘© Laboratory tet alterations in alcoholics: enhancement ofthe liver eytochrome P-450 system— A. increased synthesis of 7-glutamyltraneforase (GGT) B.__ excellent enzyme marker for alcobolic liver disease increased production of NADH in its metabolic breakdown causes biochemical reactions involving NADH to move in its direction resulting in the following ‘A. laotic acidosis: pyruvate—> lactate 'B. fasting hypoplycemia: pyruvate is unavailable for gluconeogenesis ©. hypertriacyigiyeerolemia: 1,3 bisphosphoglycerats-> dihydroxyacetone phosphate-> lycerol 3-phosphiie> TG Jmerease in ketoacid synthesis ‘A. acetyl CoA, the end product ofaleoho! metabolism ie used in the following reaction B. acetyl CoA + acetyl CoA ©. acotoacetyl Co-> "Note: This material is eopyrighted. All rights reserved. Edward Goljen, MLD. 2003 1D, IMG CoA~> acetoacetic éeid: increase in NADH converts it into P hydroxybutyric acid (8-OHB) snerease in fatty acid synthesis—dve to the increase in acetyl-CoA hyperuricemia Ietc aid/kctoacids compete with uri aed for excretion in the kidneys increased anion gap metabolic aeidosis- lactate + §-OLB Laboratory test alterations in smokers: respiratory acidosis air gets in but cannot get ou, £0 COs is retained hypoxemia (low PaO,)~ increase in PCO always causes decrease in PO: decreased O; saturation decrease in PaO, always decreases SiO; increased carbon monostde (CO) levels- CO is present in cigarette smoke secondary polyeythemia- low PaO; stimulates erythropoietin release and an increase in the production of RBCs 6. absolute neutrophilic Teukocytosis- metabolites in smoke mobilize the neutrophil ‘marginatng pool in the eirelaton by decreasing leakayte adhesion to endothelial cells 7 Tyow's petit fone of the 2 X chromosomes in a female is randomly inactivated— + 50% X chromosomes are materual, « ~50% X chromosomes patemal,# inactivated X chromosome ‘becomes a Barr body~ projection fom the naclens counted in squamous eells obtained by scrapings from the buceal mucosa 2, normal females have 1 Bars body and normal males do not have Barr bodies 3. male with Klinefelter syndrome (XXY genotype) has 1 Barr body 4. female with Turner's syndrome (XO) has no Barr bodies © Trinucleotde repent disorders: + progressively worse disease occu in future enerations (phenomenon is called anticinatin),« constant tepetition of 3 nucleotide bases (&¢, CAG, CAG, CAG ete), + more trinucleotide repeats are added each generation Teading 10 progressively worse disease and earlier manifestation of the disease, » examples Huntingtons Aisease (AD), fagile X syndrome (SXR, female carriers with winucleotide repeats eventually ‘beoame sympiomatic), Friedreich's ataxia (AD), myotonio dystrophy (AD) © Nonilisjunction: + cause of the majority of chromosome number disorders (&., trisomy 21, ‘Tumer’s XO), # de to unequal separation of chromosomes in first phase of meiosis ‘= Mosaicism: ¢ nondisjunction of chromosomes in mitotic division inthe early embryonic period, « ‘wo chromosomally different cell lines are derived from «single fertilized ey, © most cases involve sex chromosomes- eg, gonads] dysgenesis with XOMXX, XO/KY Translocation: ¢ one part of a chromosome is transfered to a non-homologous or homologous chromosome, «called a balanced translocation ifthe translocated fragment is functional, © Robertsonian translocation in Down syndrome: + type of balced translocation with » reciprocal translocation hetwcen 2 accacentic chromosomes (SOM), « usually chromosomes 21 and 14, # produces 1 long chromosome (14e2!): exiremely small translocated chromosome usually lost, * mother has the translocation: 45 chromosomes with 1 long #14e21, 1 normal #14, and 1 normal #21, » mother is normal, since both translocated fragments ate functional, « Down child receives { normal #21 from uninvolved parent (father) and 1 14621 anid 1 normal #21 fiom affected mother fora total of 46 chromosomes but all3 #21 are functioning vaPR roa ‘f ti Pdi parent: 45 chromosomes Down syndrome: 46 chromosomes ‘Note: This material fy copyrighted AU rights resorved. Edward Goljan, M.D. 2003 ee ‘CrLdu-chat: «deletion of short arm of chromosome 5, + mental retardation, «cy like x cat Microdeletion syndromes: « loss ofa small portion Fom 1 chomosome can only identitied with high resolution techniques, * microdeletion on chromosome 15 may result in tbe Prader-Willi synckome- + chromosome 15 deletion is of paterual-ottin, obesity, + hypogonadism, ment retardation, « mirodeleton on chiomosome 15 may resul in Augelnan syndrome~ = shroinosome 15 deletion is of maternal origin, + "happy puppy" syndrome (child always happy/laughing but cauno alk), «term applied to these syndeomes i genomie imprinting Genetics disorders in Africau-Americans:» sickle cell tit/lisease~ 810% prevalence of cckle call gene, * aP-thalassemia, + ghicose G-phosphste dehydrogenase (G6PD) deficiency, « Ietehtary persistence of gb ‘Genetic aisorsers in Ashkenazi Jews: «faior XI deicienoy, » Gaushet’s disease, «Tay Sache disease Genetic disorder in Norther Europeans: cystic flbrosis—MC genetic patients ability to eprodues owing to early death or problems with erty Genetic disorders in Mediterranean peoples: « GSPD deficiency,» sickle cell ait/disease, » B- thalassemia Genetic disorder in Southeast Asians: c-talassemia IMC genetie syndrome associated with advanced materual age: trisomy 21 Down syndrome pathogenesis: « trisomy 21-* 95% of all cases, * 47 chromosomes, * maternal crim for extra chromosome, Robertsonian iransloetion~ « 4%, + 46 chromosomes in eh, + smother with 45 cheomosomes- ususlly mother, » MC genetic cause of mental rtardation~ 10) 25-50 in 80% Down's clnieal findings: « eicanthal folds with ypward slanting, + simian palmar crease, + poor ‘eflexes(iypotonicity, cardiovascular- * endocardial cushion defects (combined ASD and VSD), ‘malor determining factor for survival in early infancy and childhood, « GI- + duodenal alresia (olylgdrammios, vomits bile at birt, double bubble sign on xray), * Hitschsprunzs disease.» hhomatologio- increased incidence of leukemia, « CNS- Alzheimers disease, « chromosome 21 codes for Pamyloid proteins, which are converted into amyloid and are toxio to newons, + universal by age 35 (any patient with Alzheimer's disease tnder 40 is a patient wih Down syndrome), « reproductive- * ll males are sterile, females have 50% chance of having a child swithDownts Risk for future childven with Down's: + 1-2% overall risk for trisomy 21, © matemal age- ‘Women >35 yrs of age, © 515% risk for parent with a balanced translocation, « karyotype of feted child should alivays be detetnined to evalute risk for sitlings io have affected chilies Mendelian disorders in descending order of frequency: aitosomal dominant (AD), * autosomal recesive (AR), «sexlinked recessive (SXR), «sexlinked dominant (SXD) AD disorders: + only {aboonnal allele is necessary to expres tho disease~ * "dominant gene", + ©, a2 seas, usually lethal) or Aa (Aiease), « only onc parent as to have the genic ta passit on 4 their children, + one affected parent + notmel parent 50% normal children, 50% affected children AR disorders: « both abnormal alleles mast be present (homozygous) to express the disease» a8 (Gisease), + Aa (heterozygote asymptomatic eazret),« both parents mist have the abpormal allele *2 asymptomatic carirs(children-25% normal AA, 50% Aa, 25% aa), « patient with the diseare has childcen with an asymptomatic carrer (children 50% Aa, 50% an) SXR disorders: + mates with abnormal allele express diease~ males are homozygous", since they only have 1 X chromosome,» affected males transmit the disease to both daughters but none of {heir sons~ daughters are usually asymptomatic carrcrs, «female carrier transmits the disease to 50% ofthe boys and 25% of daughters are asymptomatic carers, female cuter + affected male

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