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Lecture 1

LMP301H1 Lecture 1: Lab Tests, Cases, Water and Electrolytes, Acid-Base Disorders, Renal Disease, Lipids and Cardiac Diseases

by OneClass328331 , Winter 2016
9 Pages
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Winter 2016

Department
Laboratory Medicine and Pathobiology
Course Code
LMP301H1
Professor
all
Lecture
1

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LMP301
Introduction to the Biochemistry of Human Disease
Lecture 1 - Introduction
Disease - sickness with characteristic symptoms; response to injury
A diagnosis of disease requires objective evidence
Biochemical tests use body fluids, are relatively non-invasive, safe, and fast and accurate
Objectives of laboratory medicine
1. Define (diagnosis)
2. Predict (prognosis)
3. Monitoring
4. Find cause (etiology)
5. Screening
Mortality: causing death or reducing lifespan
Morbidity: impairs quality of life
Prevalence: number of cases of disease in a population
Incidence: number of new cases/unit time in a population
Endemic: most of the population has the disease
Epidemic: widespread occurrence of disease in a population where it’s rare
Classifications of disease:
Hereditary genetic etiology
Congenital - from birth
Injury physical or chemical stress
Infections often bacterial or viral
Inflammation
Vascular
Nutritional caused by diet
Metabolic abnormal production of enzymes/other molecules
Tumors
Iatrogenic
Psychological
Idiopathic
Purpose of testing:
Diagnostic testing
Screening for risk of a disease (e.g. heart disease, cancer)
Exclusion test
Monitoring
Others…
Lecture 2 Lab Tests
Labs in Ontario are funded by MOHLTC. Labs are divided into different areas. Turn-around time, cost,
technical expertise, and clinical need are things to consider.
Types of markers:
1. Physiological (normal range in a healthy person, tightly regulated by body)
2. Disease markers (not normally present or only in minute amounts, not regulated by body,
normally excreted)
Patient self-testing and point-of-care (POC) testing is convenient, but often costly and lacking in QC.
Testing process:
1. Pre-analytical patient preparation (e.g. fasting or diet, medications, patient factors such as
age, sex, race, pregnancy, stress), sample collecting, transporting, processing
2. Analytical sample analysis
3. Post-analytical interpretation and communication of result
Specimen type:
Red cap: serum
Green: plasma + heparin
Grey: plasma + sodium oxalate
Purple: plasma + EDTA
Sampling errors include technique, errors in timing, incorrect sampling site, etc.
Case 1: woman on diuretics shows high serum K+, but physician is not concerned
This is normal range for patients on diuretic medication.
Precise: values agree with each other, but not necessarily close to true value (usually more important)
Accurate: values close to true value
Interferences may decrease precision and accuracy
Lecture 3 Cases
The normal interval is the central 95% of a distribution from a healthy sample of 120+ individuals.
However, factors such as age, sex, and race may differ the best healthy range is the patient’s own.
This 95% interval = 2.8 x [(analytical variance)2 +(biological variance)2]
Test interpretation:
True positive
True negative
False positive
False negative
o Where true/false determines whether the test was right and positive/negative
determine the test result.
Clinical sensitivity = TP/(TP+FN)
Detects a disease when it is actually present
SnNout = SeNsitivity test, Negative result, rule OUT disease
Clinical specificity = TN/(TN+FP)
Detects absence when the disease is not present
SpPin = SPecificity test, Positive result, rule IN disease
Predictive value of + test = TP/(TP+FP)
Probability of test detecting a disease when it’s present
Predictive value of test = TN/(TN+FN)
Probability of test detecting absence when it’s absent
Efficiency = TP+TN/(TP+TN+FP+FN)
Accurately make a conclusion
Receiver operator characteristic (ROC) curves balance sensitivity and specificity
y-axis = true positive rate (sensitivity)
x-axis = false positive rate (1-specificity)
upper left corner is best

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Description
LMP301 Introduction to the Biochemistry of Human Disease Lecture 1 - Introduction Disease - sickness with characteristic symptoms; response to injury A diagnosis of disease requires objective evidence Biochemical tests use body fluids, are relatively non-invasive, safe, and fast and accurate Objectives of laboratory medicine 1. Define (diagnosis) 2. Predict (prognosis) 3. Monitoring 4. Find cause (etiology) 5. Screening Mortality: causing death or reducing lifespan Morbidity: impairs quality of life Prevalence: number of cases of disease in a population Incidence: number of new cases/unit time in a population Endemic: most of the population has the disease Epidemic: widespread occurrence of disease in a population where it’s rare Classifications of disease:  Hereditary – genetic etiology  Congenital - from birth  Injury – physical or chemical stress  Infections – often bacterial or viral  Inflammation  Vascular  Nutritional – caused by diet  Metabolic – abnormal production of enzymes/other molecules  Tumors  Iatrogenic  Psychological  Idiopathic Purpose of testing:  Diagnostic testing  Screening for risk of a disease (e.g. heart disease, cancer)  Exclusion test  Monitoring  Others… Lecture 2 – Lab Tests Labs in Ontario are funded by MOHLTC. Labs are divided into different areas. Turn-around time, cost, technical expertise, and clinical need are things to consider. Types of markers: 1. Physiological (normal range in a healthy person, tightly regulated by body) 2. Disease markers (not normally present or only in minute amounts, not regulated by body, normally excreted) Patient self-testing and point-of-care (POC) testing is convenient, but often costly and lacking in QC. Testing process: 1. Pre-analytical – patient preparation (e.g. fasting or diet, medications, patient factors such as age, sex, race, pregnancy, stress), sample collecting, transporting, processing 2. Analytical – sample analysis 3. Post-analytical – interpretation and communication of result Specimen type:  Red cap: serum  Green: plasma + heparin  Grey: plasma + sodium oxalate  Purple: plasma + EDTA Sampling errors include technique, errors in timing, incorrect sampling site, etc. + Case 1: woman on diuretics shows high serum K , but physician is not concerned This is normal range for patients on diuretic medication. Precise: values agree with each other, but not necessarily close to true value (usually more important) Accurate: values close to true value Interferences may decrease precision and accuracy Lecture 3 – Cases The normal interval is the central 95% of a distribution from a healthy sample of 120+ individuals. However, factors such as age, sex, and race may differ – the best healthy range is the patient’s own. This 95% interval = 2.8 x √ [(analytical variance) +(biological variance) ] Test interpretation:  True positive  True negative  False positive  False negative o Where true/false determines whether the test was right and positive/negative determine the test result. Clinical sensitivity = TP/(TP+FN) Detects a disease when it is actually present SnNout = SeNsitivity test, Negative result, rule OUT disease Clinical specificity = TN/(TN+FP) Detects absence when the disease is not present SpPin = SPecificity test, Positive result, rule IN disease Predictive value of + test = TP/(TP+FP) Probability of test detecting a disease when it’s present Predictive value of – test = TN/(TN+FN) Probability of test detecting absence when it’s absent Efficiency = TP+TN/(TP+TN+FP+FN) Accurately make a conclusion Receiver operator characteristic (ROC) curves balance sensitivity and specificity y-axis = true positive rate (sensitivity) x-axis = false positive rate (1-specificity) upper left corner is best Lecture 4 – Water and Electrolytes The total body water in an average person is 42L, divided into intracellular fluid (ICF), extracellular fluid (ECF), which includes the plasma and interstitial fluid (ISF) Concentration – amount of solute in volume of solvent Osmolality – amount of solute particles (i.e. if solute dissociates) in weight of solvent Osmolarity – osmolality, but solvent is water Oncotic pressure – proteins (e.g. albumin) draw out water from ISF into plasma Polyuria – lots of dilute urine Oliguria – few quantity of concentrated urine Polydipsia – drinking too much Dehydration – increased pulse (to compensate for decreased BP), dry mucous membranes, decreased + skin turgor, and decreased urine output; increased plasma Na , blood urea, hematocrit Overhydration – most features normal, edema possible; Na and other stuff become less concentrated Water regulation  Hypothalamus is the sensor  Pituitary gland secretes ADH (vasopressin) which increases resorption and constricts vessels  Renin (from kidney) and ACE convert angiotensin  angiotensin I  angiotensin II  + vasoconstriction, Na resorption, and aldosterone secretion  Aldosterone stimulates Na resorption at the expense of H and K +  Na+ is critical because as it is re-absorbed, so is water Sodium (135-145 mmol/L is normal)  Mostly stored in ECF (also bones and tissues)  Aldosterone (from adrenals) resorb Na from kidney  ANP (from atria of heart) excretes Na+  Hypernatremia is too high [Na ] o Loss of solutes drags water along with it – dehydration o Hyperaldosterone - Conn’s, Cushing’s – too much Na resorption +  Hyponatremia is too low [Na ] o Renal failure – not eliminating enough water o Adrenal insufficiency – Addison’s  Edema – too much water in ISF o Body increases ADH and aldosterone as it thinks it’s low in circulating water o Volume overload – heart failure and hypoalbuminemeia  Approach is to identify Na status, water status, input/output of Na , and organ functions  Treatment is infusion of isotonic solution (5% dextrose, 0.9% saline, or plasma) Potassium  Mostly stored in ICF  Hyperkalemia o Acidosis o Cell lysis/damage (remember majority is in ICF) o Kidney failure + o Excess K intake o Aldosterone (mineralocorticoid) deficiency  Hypokalemia o Alkalosis o Aldosterone excess + o Certain drugs that cause excess K secretion  Pseudokyperkalemia o Cell rupture during sample extraction o White blood cells/platelets (e.g. coagulation is currently happening) Lecture 5 – Acid-base Disorders + [H ] is normally 35-45 nmol/L or pH = 7.35-7.45 PCO i2 normally 40 mmHg - [HCO ]3is normally 25 mmol/L Outside this range usually indicates something wrong (e.g. hypoxia, ketoacidosis, alkalosis, poisoning, lung and/or kidney failure) H is produced from metabolism, especially S-containing proteins. + + + Excess H is removed via lungs (CO ) and 2idney (H and NH ) 4 Either system can compensate if the other fails The body’s main buffers are HCO , plasma proteins and hemoglobin, intracellular proteins. + -
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