MODULE 1 OBJECTIVES.docx

MODULE 1 OBJECTIVES By the completion of the module students should be able to: Top of Form Explain the fields of Pathology and Laboratory Medicine Anatomical pathology: surgical- study of tissue removed from living patients during surgery to help diagnose a disease and tx plan forensic- med doc...

MODULE 1 OBJECTIVES By the completion of the module students should be able to: Top of Form Explain the fields of Pathology and Laboratory Medicine Anatomical pathology: surgical- study of tissue removed from living patients during surgery to help diagnose a disease and tx plan forensic- med doc, who investigates unexpected, unnatural or voliet deaths Cytopathology - examining cells from bodily tissue or fluid to determine diagnosis molecular pathology- diagnosis of disease through examination of organs, tissue or bodily fluids Clinical pathology: clinical chemistry- focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using microbiology- study microorganisms that cause infections and diseases. blood bank/hematology- blood products in hospital immunology- specialise in diagnosing and treating patients with inherited or acquired failures of the immune systems that lead to infections and autoimmune complications (immunodeficiency disorders) and autoimmune diseases and vasculitis where the body harms itself. Discuss specimen collection and appropriate sampling for the diagnosis of various diseases Specimen Collection Possible tests Blood Drawn by finger prick/ needle Cell counts, electrolytes, protein (ex. Troponin, tumour markers), markers of inflammation, liver/kidney function tests and genetic tests Urine Random clean catch, sterile urine test Blood, leukocytes, protein, drugs or organisms Sputum Coughed into container Culture (bacteria) , cytopathological exam Stool Plastic container Blood, ova, and parasites Other body fluids Spinal fluid, pleural or peritoneal fluid, joint aspartate and bone marrow Culture, cytopathological exam Cytopathology: Types of samples: Exfoliative Interventional Spontaneous - Pleural or peritoneal fluid - septum/ urine Fine needle aspiration - lymph node - thyroid Mechanical - cervical pap smear Bronchial brushing (endoscopy) Assess the pre-analytical specimen collection process in order to reduce errors What can be tested by the lab? Most fluids and cells containing biological components such as enzymes, metabolites, nutrients, minerals, trace elements, proteins, nucleic acids and DNA that have diagnosis applications Most common specimens are: BLOOD AND URINE More specialized materials include: Sweat, spinal fluid, joint fluid, saliva, hair, feces, bone marrow, and liver tissue etc. BLOOD TESTS: 2 main methods to collect species Finger prick Venipuncture Specimens’ collection: to obtain accurate test results it’s important to collect the proper specimen type in the correct tub and follow the correct order of draw. Order of draw Specimens’ collection: SERUM: Blood samples are collected Without an anti-coagulant (red top) Allow the blood to clot (takes 30 mins) Then centrifuged and separate from the cells Serum separation tube (SST) has a gel layer that provides a physical barrier between the serum and cells after centrifugation (gold top) – This allows much better stability of analytes and allows for transport of a spun tube PLASMA: Blood samples are collected: With heparin to prevent clotting (green top) then centrifuged and separated from the cells. Do not require sample to clot before centrifugation Advantage: faster sample processing and smaller sample volume Blood collected: With EDTA to preserve cellular elements of blood (lavender top) Used for hematology tests such as CBC But not good for tests For divalent elements such as Ca or Mg, whicih are bound by EDTA For enzymes which requires these ions as co-factors URINE: Random Timed sampling (e.g., 24 h) SPINAL FLUID, CHEST FLUID, OR LIVER BIOPSY: Are collected by a physician Importance of preanalytical phase of laboratory testing: Most lab errors occur in the preanalytical phase of testing (over 66% reported in literature) Incorrect sample type Ensure correct order of draw Under-filling tubes Ensure tubes are mixed appropriately after collection Sample hemolysis Extreme temperature exposure/ storage conditions Delayed transportation Time from collection to processing or analysis Ensure lab receives a quality specimen is key to reporting of accurate results to the clinical team Outline the pathway of a specimen through Pathology and Laboratory Medicine Surgical pathology; Gross (macroscopic) exam of organs and tissues Biopsies e.g. Skin, cervix and breasts Surgical resections Histological (microscopic) exam Generation of a diagnostic pathology report Techniques in pathology: Gross exam Exam of a specimen with a naked eye Microscopic exam Light microscopy Cell morphology Electron microscopy Changes in organelles Ancillary tests Immunohistochemistry Special histochemical stains Molecular pathology Immunochemistry: Selectively identifies proteins in cells to aid with diagnosis Special histochemical stains: Highlight specific tissues (eleastic tissue, collegen) Pigment (iron, melanin) Microorganisms Molecular pathology: The detection and/or analysis of nuceli acid molecules (dna/ rna) to provide clinical information Chromosomal analysis Dna sequencing Type of testing Constitutional genetic disorders Metabolic disorders Hereditary cancer panels- genetic predisposition to cancer Solid tumor testing- treatment purposes Pathology reporting Diagnosis: Uterus, hysterectomy: Endometrial endometrioid adenocarcinoma Myometrial invasion to 80% of the myometrial thickness No cervical stromal invasion Lymph vascular invasion present Stage pT1b  5. Apply the concept of Choosing Wisely and how it relates to laboratory stewards Describe the utility of lab tests Why are laboratory tests requested? Diagnosis of a disease: e.g., Diabetes mellitus test: serum glucose Screening for a disease: e.g., screen for PKU (phenylketonuria) in newborns for deficiency of phenylalanine hydroxylase Determine severity of an illness: e.g., serum K needed for nerve transmission in heart and for muscle contraction normal range 3.5-5 mmol/L (Serum Potassium) critical levels <3.0 or >6.0 mmol/L (may imply a life-threatening condition) determine appropriate management e.g., Prostate cancer- prostate specific antigen (PSA) is used to monitor patient for post- surgical recurrence of tumor monitor progress of surgical recovery e.g., kidney transplant – creatinine and other renal function tests Therapeutic drug monitoring E.g., digoxin is effective at 1.0-2.7 mmol/L, but toxic >2.7 mmol/L with heart block and arrythmia Identify drugs of abuse or poisoning E.g., cocaine, cannabinoids (marijuana metabolites) Assessment of baseline or nutritional status E.g., serum prealbumin to monitor protein malnutrition Protection against legal repercussion s i.e., was normal clinical practice followed? E.g., was blood lead measured in a porphyria patient? Re-test to verify abnormal results If a test result doesn’t fit with history or symptoms If there are suggestions of a sample mix- up If a significant therapy depends upon the findings  7. Define lab test performance issues (e.g., accuracy, precision, predictive value, sensitivity, specificity) Accuracy and precision: Accuracy describes the ability of data, measurements or results to match the actual ‘true’ value. Precision is how close these data, measurements or results are to each other, working as a measure of the spread of data from the average Test interpretation and performance: Lab tests are often used to confirm (rule in), or exclude (rule out) a disease. As shown in the diagram below for “non-disease”, the decision threshold line (or cut off value) at the upper limit of the reference range (or interval) must be determined. If this is a selected point, then values below the decision threshold are described as the true normal (TN) and those above are false positive (FP) values Specificity: In considering a non-disease population, the term specificity is used to describe the absence of disease. As the TN is increased (arrow to the right) and the FP is decreased, the specificity of a test is improved. A good test gives negative results in non-diseased subjects. Specificy = TN__________ TN + FP________ Sensitivity: In the grph below, a population of subjects with the disease is shown with the decision threshold. Those above this cut-off are defined as tur postivie (TP) and those below the threshold as false negative (FN). The term sensitivity Is used to describe the power of the test which gives a positive result in diseased subjects. Sensitivity = TP TP + FN Test interpretation: Specificity: Percentage negativity of test results in patients who are free of disease. TN/TN+FP x100 Sensitivity: Percentage positivity of test results in patients who have the disease. TP/TP+FN x100 Both specificity and sensitivity are dependent upon the decision threshold selected or used. Positive Predictive Value (PPV): The percent probability that a positive test result correctly predicts the presence of disease. TP/TP+FP x100 Negative Predictive Value (NPV): The percent probability that a negative test result correctly predicts the absence of disease. TN/TN+FN x100 Effects of prevalence on the predictive value of a test: Prevalence is defined as the percent of patients who have the disease that is being tested. The predictive value of a test changes with a change in the prevalence of the disease in the population A fairly good test with a sensitivity of 95% and specificity of 95% can have a different predictive value based on the percent of patients with the disease 2 x 2 Decision Matrix: Effect of prevalence: Receiver Operating Characteristic (ROC) Curves: A graphical means to assess a test’s performance was used during WW II to examine the sensitivity and specificity associated with the radar detection of enemy aircraft, called the receiver operating characteristic curve. This is a plot of the false positive rate (1-specificity) against the true positiverate (sensitivity). Several decision threshold values (from low to high) are selected and the sensitivities and specificities are calculated for each, and plotted.  8. Discuss the importance of laboratory test utilization Selective use of laboratory tests to provide the clinician with the most relevant information Strategies to improve lab tests utilization include Drop ‘shot gun’ biochemistry profile screens Order single or discrete single tests Order only tested related to the specific disease \ Don’t order a test ‘STAT’ unless specifically required Reflex testing can improve disease diagnosis An abnormal result on a “specific” test reflexes to a “sensitive” test E.g., a serum protein electrophoresis which shows an abnormal band can be followed with immunofixation to identify the band Review utility and impact of specialized or high-cost tests. Test results may take a long time to come back. How does this impact treatment or care of the patient. Education is needed for test interpretation or “unexpected” results Effects of preanalytical issues (sample hemolysis) Interfering substances E.g., adjust serum Ca upwards by 0.2mmol/L for each 10g/L decrease in serum albumin Apply algorithm for disease investigations Other tests may still be required to exclude a disease, but pathophysiological relationships are needed to connect the tests with the disease LABORATORY STRWARDSHIP: Apply the concept of Choosing Wisely and how it relates to laboratory stewardship Laboratory stewardship refers to the appropriate utilization of laboratory tests which encompasses correctly ordering, retrieving, and interpreting these tests Choosing wisely Canada: National organization Dedicated to reduction of testing and effectual resource use Engagement of health care professionals to make smart and effective care choices Public heath care interest Stewards of public resources Why is this necessary? Unnecessary Testing: Up to 30% of tests, treatments and procedures performed in Canada are potentially unnecessary Why does unnecessary testing, procedures and treatments occur? Task # 1 • Navigate to the choosing wisely recommendations for pathology and familiarize yourself with the “Five things physician and patients should question” Don’t perform population based screening for 25-OH-Vitamin D deficiency. Don’t screen with Pap smears if under 21 years of age or over 69 years of age. Avoid routine preoperative laboratory testing for low-risk surgeries without a clinical indication. Avoid standing orders for repeat complete blood count (CBC) on inpatients who are clinically/laboratorily stable. Don’t send urine specimens for culture on asymptomatic patients including the elderly, diabetics, or as a follow up to confirm effective treatment. Patient Resources: Using plain language and materials to help explain rationale for reduced testing is important Helps patients to learn about tests and treatment Advises when tests are necessary and when they are not Advice for patients to improve health Bottom of Form Task # 2 Navigate to the choosing wisely Canada patient pamphlets page https://choosingwiselycanada.org/patient-pamphlets What patient resources might be pertinent to Pathology and Laboratory medicine? Highlight specific recommendations for these tests. Some information sheets may include: Lab testing before surgery Pap tests Self-monitoring blood sugar for type 2 patient with diabetes not on insulin Vitamin D tests Colonoscopy Errors in Pathology: Assess the pre-analytical specimen collection process in order to reduce errors Errors in laboratory medicine: Pre- analytical Errors in Pathology: Causes of disease: Disease classification “VITAMIN CDE” Define and use common pathology terminology to describe various aspects of disease Classify the categories of disease and provide examples in each category Explain basic terminology and pathology processes in lay language to a patient Definition to set the foundation: Pathology The study of disease The study of the structural and functional changes in cells, tissues, and organs of the body that cause or are caused by disease Derived from: pathos = disease or suffering logos or logia = study Disease The pattern of response of living organisms to injury Any deviation from, or interruption of, the normal structure or function of a tissue, organ or system When cells fail to adapt to the injury, or the adaptive mechanisms itself becomes harmful, disease results Disease results from some disturbance to cells as a result of: Physical insult Environmental insult Genetic aberration (inherited or acquired) Recognized by signs and symptoms Signs and symptoms help indtifiy disease: Sign: Clinical signs that can be objectively observed or measured by a physican or nurse Alteration of a physiological, biochemical or morphological parameter Symptoms: Subjective complaints described by the patient Understanding and Describing Disease: Disease Classification – Based on cause Genetic or congenital factors: Alterations in genetic material Single mutation in a DNA base pair Sickle cell disease Additions/deletions/rearrangements of whole chromosomes Trisomy 21 (down syndrome) Not all inherited (genetic) disease manifest at birth Huntington disease Not all congenital diseases are genetic Congenital = present at birth Infections in utero Rubella or measles in mother can result in cataracts, microcephaly, heart defects in newborns Genetic or congenital factors Congenital anomalies Structural or functional defects that occur in utero and are present at birth May or may not have genetic cause Malformation Intrinsically abnormal development process Deformation Secondary destruction of an organ or body region that was normal in development Extrinsic disturbance Secondary or extrinsic destruction of the normal development process Ex. Localized or generalized compression of growing fetus by biomechanical forces Results is structural abnormalities Forces include: Small uterus Large fetus Oligohydramnios Teratogens Environmental factors causing development or congenital anomalies Environmental Factors: Disease classification -based on pathogenesis: Idiopathic: Unknown etiology Currently no known cause Causes may emerge through further investigation Ex: Idiopathic hypertension, idiopathic pulmonary fibrosis Iatrogenic: Disease or any adverse condition resulting from treatment by a health care professional Adverse events Unintended injury or complication resulting in death, disability or prolonged hospital stay *Important causes of morbidity and mortality Improvements in patient safety are needed Adverse drug events Wrong medication Wrong dose Harmful drug interaction Adverse surgical events Wrong procedure Sponges left in patient following surgery Other adverse events while hospitalized Development of bed sores in immobile patients Hospital acquired or nosocomial infections Mortality and Morbidity of Canadians Define and distinguish between morbidity and mortality and outline the major causes in Canada Impact of Disease Morbidity Illness or impairment/disability caused by disease Something that impairs the well-being or normal functioning of a patient Mortality Something causing the death of a patient (death from disease) Expressed as “rates”: actual # of persons affected or age-adjusted rates per 100 000 persons Hospital stays in Canada Leading cause of hospitalization: 2019-2020 Life expectancy: Life expectancy has been steadily increasing in Canada Increase of about 25 years in life expectancy since 1921 Reasons? Improvements in policies and practices: Sanitation Medical care – advance in surgical and medication-related treatments Reduced deaths from cardiovascular diseases account for most increases in life expectancy since 1951 Public awareness of good nutrition and the health risks associated with smoking Community advocacy efforts concerning drinking and driving and seatbelt use Pre-natal and post-natal care, childhood vaccinations Nearly half of all the gains in life expectancy occurred in the period between 1921 and 1951, largely due to reduced infant mortality Disease Mortality Top 5 causes of death in Canada in 2019 1. Malignant Neoplasms 2. Disease of heart 3. Accidents (unintentional injuries) 4. Cerebrovascular diseases 5. Chronic lower respiratory diseases Canadian Cancer Statistics: Canadian Cancer Statistics Males more likely to be diagnosed with cancer Females more likely to survive cancer when compared to males 90% of cancer diagnoses occur among Canadians who are at least 50 years of age The Definition and Causes of Disease - Key Terms congenital - present at birth chromosomal abnormalities - a change in the normal number of chromosomes or in their normal structure. (Normally, there are 46 chromosomes in total - 22 pairs plus 2 sex chromosomes (either XX or XY) ex. 46,XX or 46,XY)  disease - very simply, a change in normal body function/structure that leads to abnormal function (e.g., resulting from a direct insult, such as trauma or infection, or an indirect insult, such as a disturbance in metabolism) etiology - the study of the cause(s) of disease genetic - a heritable disorder iatrogenic - disease caused as the result of a medical treatment idiopathic - of unknown origin; used when we don't know the cause of disease incidence - the number of new cases of disease or illness in a given population in a given time period morbidity - the impairment of health by illness mortality - causing the death of the patient; mortality rate = the number of individuals who die from a given disease pathogenesis - the stages through which a disease progresses; the production and development or mechanism of disease; the sequence of cellular events that take place from time of initial contact with the etiologic agent until the expression of the disease pathology - the study of disease (i.e., causes, typical characteristics, and effects) prevalence - the total number of cases of a given disease or illness in a population for a given time period or at a given point in time (point prevalence) prognosis - the most likely course and outcome of disease sign - an objective measure found upon physical or clinical examination (e.g. body temperature, blood pressure, pulse, weight, edema, blood glucose) symptom - a subjective complaint from a patient, i.e. not measurable (e.g. fatigue, nausea, pain, dizziness) teratogen - a chemical (e.g. drug, alcohol), biological (e.g. rubella) or physical agent that causes physical defects in the embryo Case study: Part 1: Errors in Pathology Gastroenterology Clinic You are the nurse in Dr. Wright’s gastroenterology clinic. Today there is a long list of patients undergoing colonoscopy procedures so you are preparing for the patients ahead of time by printing all of the patient specimen labels for the day and labeling them “colon”. Once printed, you line up all of the specimen containers and put the specimen labels on them. Question: What are the possible sources of error with this process and how would you avoid it? The first patient enters the endoscopy suite, you greet them and direct them to the examination table. Question: What initial steps should be taken to reduce pre-analytical error? The next week you are working with Dr. Wright in his clinic and the patient’s who previously had a colonoscopy are back for their follow-up visit. Amit, a 45 year old male is returning to clinic. You are remembering back and reviewing Dr. Wright’s clinic note and see that at the time of the colonoscopy, Amit was having irregular bowel movements with cycling episodes of diarrhea and constipation. The colonoscopy was normal and Dr. Wright took one representative rectal biopsy (3 mm). You review Amit’s Pathology report. PATIENT: Amit Chandra Medical Record #: 254380 Specimen Collection Date/Time: 05/13/2021 13:24h Specimen receipt Date/Time: 05/13/2021 14:30h Date of Birth: 02/07/1976 Sex: Male Case #: S-21-6859 PATHOLOGY REPORT Specimen Label(s): Patient history: Pre-operative diagnosis: Ascending colon Anemia and colon mass ?rectal cancer DIAGNOSIS: Colon (ascending), biopsy: Colonic adenocarcinoma, well-differentiated GROSS DESCRIPTION: A: The specimen and patient identifiers are reviewed and are verified. Specimen: tan polypoid piece of tissue Number: 1 polypoid piece Size: polypoid piece(s) 1.5 cm Section code (entirely submitted): (A1-A2) polyp bisected Question: What are the possible pre-analytical errors and what are the clues in the pathology report? Question: What is the major concern with this case? Claire is now entering the clinic room. She is a 65 year old female who has been having rectal bleeding. From the colonoscopy procedure note, she had a large polyp that was removed at the time of colonoscopy. You check for the pathology reports and see that there was no pathology ordered for this patient. List the possible pre-analytical causes for this. Part 2: Morbidity and Mortality Cancer Specific Stats: https://cdn.cancer.ca/-/media/files/research/cancer-statistics/2020-statistics/canadian-cancer-statistics/2020-resources/res-cancerstatistics-canadiancancerstatistics-2020_cancer-specific-stats.pdf?rev=a672053690e9493d921fe73453a749b4&hash=4F194657DA83EFC15ADB92A8E5ACBC5E Cancer Incidence and Mortality Navigate to the link: Cancer-specific stats 2020 Which cancers have the highest incidence (top 5) for: Both sexes? Males? Females? Highest incidence Both sexes Male Female 1 2 3 4 5 Navigate to the link: Cancer-specific stats 2020 Which cancers have the highest mortality (top 5) for: Both sexes? Males? Females? Highest Mortality Both sexes Male Female 1 2 3 4 5 Navigate to the link: Cancer-specific stats 2020 Which cancers appear on the highest mortality (top 5) list, but not on the highest (top 5) incidence list for: Both sexes? Males? Females? Both sexes Male Female Navigate to the link: Cancer-specific stats 2020 Which cancers appear on the highest incidence list (top 5) list, but not on the highest (top 5) mortality list for: Both sexes? Males? Females? Both sexes Male Female What is the general trend in incidence and mortality for the top three cancers in males and females? What cancer has the worst prognosis and what is the trend in incidence and mortality?