THE UNIFIED FIELD THEORY OF DIABETES, CLINICAL CHEMISTRY, AND EVERYTHINGBY CHAD GUILLIAMS, M.

ED., MLS(ASCP)CM

OUTLINESigns, Symptoms, ComplicationsSelling SicknessCarbohydrates PancreasType I vs Type II DiabetesWater/Osmolality/Electrolytes Acid-Base DisordersLipidsHeart DiseaseRenal Disease

http://memekid.com/funny-chemistry-cat-memes.htm

SIGNS, SYMPTOMS, COMPLICATIONS

http://www.md-reasons.info/2014/07/diabetes-complications-of-diabetes.html

SELLING SICKNESS

Ill Defined Diseases Affect numerous people High Cholesterol and

Diabetes

Drug Companies ProfitsExpand boundaries of illnessNew customers

DiabetesBefore 1997 Diabetes diagnosis fasting blood

glucose > 140 mg/dLAfter 1997 Diabetes diagnosis fasting blood glucose

> 126 mg/dL

CholesterolBefore 1998 High Cholesterol > 240 mg/dL After 1998 High Cholesterol > 200 mg/dL

Increased new customers by 86%

Lifestyle changesDiet and Exercise

CARBOHYDRATES

Types of Energy the body can useCarbohydratesProteinsLipids

Carbs are Good

CarbohydratesGlycemic indexInsulin Response

DefinitionsGlycolysisGlycogenesisGlycogenolysisGluconeogenesis – ATP and Pyruvate

http://www.rogerspeakperformers.com/2012/the-glycemic-index/

PANCREAS

Anatomy of a PancreasExocrine – digestive enzymes amylase and lipase

Increased in pancreatitis (lipase more specific)

Endocrine - Islets of Langerhans Beta Cells – Insulin Alpha Cells – Glucagon Delta Cells – Somatostatin

InsulinAllows glucose to enter cellsOnly hormone than can decrease glucose

levels

GlucagonPrimary hormone responsible for elevating

glucose levels

http://www.medicinenet.com/image-collection/pancreas_picture_1/picture.htm

PANCREAS REVIEW

When the body has an excess of glucose it will go through the process of:A) Decreasing cell membrane permeability

B) Gluconeogenesis

C) Glycogenesis

D) Glycogenolysis

Glucagon acts by:A) Increasing glycogenolysis

B) Increasing glycogenesis

C) Increasing glycolysis

D) Inhibiting glycogenolysis

TYPE I VS TYPE II

Type I AKA insulin dependent diabetes (IDDM)Mostly young and thinLittle to no insulin produced – autoimmune destruction

Diabetic ketoacidosis - common

Lab findings• Blood glucose levels 300-500

mg/dL• Ketonuria• Ketonemia• Decreased Na and Cl• Increased K• Slightly increased osmolality

Type II non insulin dependent diabetes (NIDDM)Most common form found in mostly older and obese adults

Combination of Insulin resistance and Insulin production issues

Diabetic ketoacidosis – rareHyperosmolar comaLab findings

Blood glucose levels >1000 mg/dL Greatly increased osmolality

http://www.psychiatrictimes.com/metabolic-disorders/metabolic-monitoring-patients-antipsychotic-medications/page/0/4

MONITORING DIABETES

Glucose – serum, plasma, whole bloodPreferred diagnosis test is fasting plasma glucose (fasting 10 hours prior)• Reference range 70 -110 mg/dL

Glycosylated hemoglobin or HbA1C – average glucose over 3 monthsWhole blood EDTA tube

Ketone levels – serum or urine – acetest sodium nitroprusside (detects acetoacetic acid)

Microalbuminuria – minute concentrations of albumin in urine (early signs of nephropathy)

http://blog.diabetesms.com/?cat=3

CARBOHYDRATES REVIEW

Jane Doe is a 55 year-old-female. Her lab results were:Fasting glucose 122 mg/dLFasting triglycerides 144mg/dL

All other lab tests were normal. The doctor ordered a 2 hour OGTT. The 2 hour glucose tolerance test result was 228 mg/dL. These results indicate:

A) Results are normalB) Diabetes mellitusC) HypoglycemiaD) Ketoacidosis

Monitoring long-term glucose control in patients with adult onset diabetes mellitus can best be accomplished by:

A) Urine microalbuminB) Glucose tolerance testingC) 2-hour postprandial serum glucoseD) Glycosylated hemoglobin

CARBOHYDRATES REVIEW

WATER

Average Water Content of the Human Body is 40% to 75% of total body weight.Intracellular fluid – two-thirds of total body water

Extracellular fluid – one-third of total body water (Intravascular and extravascular fluid)

Intravascular fluid plasma (93% water)Carries proteins, electrolytes, nutrients, hormones,

wastes

What must be kept in a constant concentration in the body is:Electrolytes (ions)

pH (acid-base balance)

Water

http://www.apswater.com/article.asp?id=129&title=What+are+the+chemical+properties+of+water?

OSMOLALITY

Is a physical property of solution that is based on the concentration of solutes (particles) per kilogram of solvent

Measured Osmolality is done using freezing point depression

Reference Range Serum 275-295 mOsm/kg

General indicator of water volume

Calculated osmolality (mOsmol / kg H20) =

2 [Na+ ] + [glucose] /20+ [BUN]/3

WATER VOLUME REGULATION

Plasma osmolality directly effects the hypothalamus

Increase osmolality increases thirst

Increase osmolality increases ADH secretion from the posterior pituitary

Decreased osmolality decreases ADH secretion

Deficiency of vasopressin (ADH)

Diabetes Insipidus

Results in large volume of dilute urine

Renin-angiotensin-aldosteroneStimulates sodium reabsorption

and potassium excretion http://pixgood.com/adh-kidney.html

WATER VOLUME REGULATION

Water deficitOsmolality increases (electrolytes

concentrated)

Increased thirstADH is secreted

• Increases water reabsorptionAldosterone is inhibited• Less sodium reabsorbed = decrease in

electrolytes

Water overloadOsmolality decreases (electrolytes diluted)Thirst suppressedAldosterone secreted• Sodium is reabsorbed = increase in electrolytes

ELECTROLYTES

Remember two basic types of dehydrationDying of thirst in the desert – losing more

water relative to electrolytes

• Lab findings – all electrolytes elevated

o Hypernatremia

o Hyperosmolality

Vomiting and Diarrhea – losing more electrolytes relative to water

• Lab findings – all electrolytes decreased

o Hyponatremia

o Hyposmololality

https://www.cartoonstock.com/directory/t/thirsty.asp

ELECTROLYTES

Anions have a negative charge Cations have a positive charge Extracellular fluid has a high concentration of Na+, Cl-, HCO3-

Intracellular fluid has a high concentration of K+, Ca+, Mg+, PO4-Hemolysis is unacceptable for these tests

Sodium – osmolality = blood volumeMajor extracellular cation 135-145 mEq/LHyponatremia• With low serum osmolality – diarrhea, vomiting, diuretics• With normal serum osmolality – in vitro hemolysis• With high serum osmolality – hyperglycemia

Hypernatremia• Dehydration, diabetes insipidus (dilute urine),

hyperaldosteronism

ELECTROLYTES

Potassium – myocardial contraction Major intracellular cation 3.4 – 5.0 mmol/L (20X

greater inside cell than outside)• HEMOLYSIS IS UNACCEPTABLE

Both high and low levels will stop the heart Hypokalemia• Vomiting, diarrhea, hyperaldosteronism

Hyperkalemia• Hyperglycemia, hypoaldosteronism (Addison’s disease)

Chloride – maintain electrical neutrality (chloride shift)Major extracellular anion 98-106 mmol/LPassively follows sodium increased and decreased in

the same conditionsSweat chloride test for cystic fibrosis –

iontophoresis/pilocarpine http://www.cdha.nshealth.ca/pathology-laboratory-medicine/clinical-chemistry/hemolysis

ELECTROLYTES

Bicarbonate (HCO3-) – buffering system maintain pHSecond most abundant anion in extracellular fluid

22-29 mmol/L

Measured as total CO2 • 90% of total CO2 is bicarbonate

Acid base imbalance• Decreased metabolic acidosis

• Increased metabolic alkalosis

Exposure to air will decrease CO2

Electrolytes analysis Ion selective electrode – potentiometry using

Nernst equation Susceptible to protein build up

Sodium analysis selective membrane Glass ion-exchange

Potassium analysis selective membrane Valinomycin

Chloride analysis selective membrane Ion exchange

Carbon dioxide (bicarbonate) PCO2 electrode

http://chemwiki.ucdavis.edu/Analytical_Chemistry/Analytical_Chemistry_2.0/11_Electrochemical_Methods/11B%3A_Potentiometric_Methods

ELECTROLYTES

Anion GapDifference between unmeasured anions and

unmeasured cations

Reference range: 10-20 mmol/L Used as a form of QC High anion gap common in ketoacidosis

ELECTROLYTES

The anion gap is calculated as follows:

[Na+] – ([Cl- ] + [HCO3- ])

or([Na+] + [K+ ] ) – ([Cl- ] + [HCO3

- ])

Hyponatremia with a high osmolality is most commonly seen inA) DiarrheaB) Renal FailureC) In Vitro HemolysisD) Hyperglycemia

In dehydration which of the following hormones is responsible for increasing water reabsorption in the tubules:A) Antiduretic HormoneB) AldosteroneC) RenninD) Thyroxin

WATER ELECTROLYTEOSMOLALITYREVIEW

ACID-BASE DISORDERS

CO2 ≈ acid

As CO2 increases = pH decreases

As CO2 decreases = pH increases

HCO3- ≈ base

As HCO3- increases = pH increases

As HCO3- decreases = pH decreases

http://groups.csail.mit.edu/medg/people/psz/PatilThesis81/Patil81_ch1.html

Bicarbonate-carbonic acid buffer system

Normal pH reference range is 7.35-7.45

pCO2 (35-45 mmHg)

HCO3 (22-26 mmol/L)

Acidosis or AlkalosisDetermine what is causing the problem

Respiratory or Metabolic (renal)

Respiratory problemIf pH and PCO2 are opposite each other

• pH PCO2

• pH PCO2

Metabolic problemIf pH and HCO3- go up together or down together

• pH HCO3-

• pH HCO3-

ACID-BASE DISORDERS

Other normal system can then compensate (compensatory system)

If Respiratory system• Hypoventilate • Hyperventilate

If Metabolic system• Excrete or reabsorb H+

• Excrete or reabsorb HCO3-

Look at compensatory system reference range

for either HCO3- or CO2Uncompensated (value within normal range)Partially compensated (value outside of normal range)Compensated (value outside of normal range and pH

within normal range)

CollectionHeparinized syringe radial arteryNo Bubbles or exposure to air http://www.rtmagazine.com/products/blood-gas-analysis/

ACID-BASE DISORDERS

Break it down Acidosis or alkalosis? Problem organ system? Is the other system compensating?

ABG problem Review pH 7.26 pCO2 16 mmHg HCO3- 7.1 mmol/L

ABG problem ReviewpH 7.60pCO2 25 mmHgHCO3- 24 mmol/L

ACID-BASE DISORDERS

LIPIDS

Unsaturated Fat 3

Saturated FatHydrogenation form of preservationTrans FatSolid at room temperature

http://www.indiana.edu/~oso/Fat/trans.html

http://www.med-health.net/Olive-Oil-Ear-Wax.html

https://www.flickr.com/photos/fotoosvanrobin/11026441715/

LipidsOrganic compounds insoluble in waterFatty acidsTriglycerides Cholesterol

Fatty AcidsBody makes mostEssential fatty acids -not made by the body• Omega 3 and Omega 6

Triglycerides Majority of what we eat Lots of calories

CholesterolPresent in all cell membranes Building block of bile and steroid hormonesLiver makes most of what we need

Fat stored as Triglycerides in adipose tissueLipolysis – break down of fat for energy Ketone bodies

LIPIDS

Lipoproteins from largest (least dense) to smallest (most dense)

Chylomicrons• Largest lipoprotein least dense• Transport dietary lipids from the small intestine to the liver• Causes turbidity in serum

VLDL• Contains mostly triglycerides• Transports triglycerides from the liver to peripheral tissue

LDL• Delivers cholesterol to cells• Contains mostly cholesterol• BAD cholesterol associated with Apoliprotein B• High levels of LDL and Apo B risk of heart disease

HDL• Removes cholesterol out of cells• GOOD cholesterol associate with Apoliprotein A• High levels of HDL and Apo A risk of heart diseasehttp://dolinabiotechnologiczna.pl/diagnostyka-laboratoryjna-2/ratunku-

lipemia/

LIPIDS

LIPID REVIEW

Which of the following lipoproteins is the major carrier of cholesterol to peripheral tissues?A) VLDLB) LDLC) HDLD) Chylomicrons

True or False:

Increased levels of apolipoprotein A-I are associated with increased risk of

coronary artery disease.

http://investorplace.com/2014/03/bacon-smell-oscar-mayer-aapl-stock-krft-stock/#.VT01CWN8MXk

Lipid panel includes (fasting 10-12 hours)Total cholesterol - measuredLDL – calculated using Friedewald calculation• LDL = total cholesterol – (HDL + VLDL)• Invalid Trig > 400 mg/dL

HDL - measured

Triglycerides – measured • High levels increase risk of pancreatitis

Arteriosclerosis – hardening of the arteriesIf it affects the heart called Coronary Artery

Disease

http://healthinformatics.wikispaces.com/Balloon+Angioplasty

CORONARY ARTGERY DISEASE

HEART DISEASE

Initial Cardiac Panel includes:

Troponin - Most specific cardiac marker• Troponin I (TnI) increases 4 hours normal after 6 days• Troponin T (TnT) increases 4 hours normal after 7 days

Total CK – nonspecific marker • Found in all muscle increased in rhabdo, MD

CK-MB (isoenzyme)– second most specific cardiac marker• Peaks in 1 day returns to normal in 2 days

Myoglobin – least specific marker• Sensitive rises within 1 hour returns to normal in 1 day• Early indicator• Not included on subsequent cardiac panels only initial

http://dietchoices.com/diet-plans/heart-attack-grill-diet/

HEART DISEASE REVIEW

Which of the following tests monitors inflammation levels that may contribute to acute coronary syndromes?

A) hs-CRPB) Troponin IC) BNPD) Total CK

OTHER CARDIAC MARKERS

hsCRP – high sensitivity C-reactive protein Measures inflammation related to stress

(cortisol)• Increased hsCRP = increased plaque formation

BNP – B natriuretic peptideIncreased in CHF

RENAL SYSTEM

Elimination of waste Urea• Protein degradation = ammonia =urea

Creatinine• Waste product of creatine• Jaffe reaction

o Ketones positive interference Falsely elevate creatinine levels

Uric Acid• Final product of purine metabolism• Monosodium urate crystals synovial fluid = gout

o Polarized microscope

Glomerular Filtration Rate 24 hour urine Creatinine Clearance

U x V x 1.73S 24V SA

Creatinine Clearance =

RENAL DISEASE

Normal Kidneys Serum• Normal levels of BUN and Creatinine

Urine• Concentrated • High in BUN and Creatinine• Little to no protein

Abnormal Kidneys - Renal FailureSerum• High levels of BUN and Creatinine

Urine • Dilute low specific gravity

• Low in BUN and Creatinine• High in protein

o Microalbuminuria – early indicator diabetic nephropathy

o Renal failure will result if diabetes is not well managed http://www.rayur.com/acute-renal-failure.html

CASE STUDY

REFERENCES

Bishop, M.L., Fody, E.P., & Schoeff, L. E. (Edward P Fody MD). Clinical Chemistry: Principles, Tehcniques, and Correlations. Philadelphia:

Lippincott Williams & Wilkins.

Moynihan, R., & Cassels, A. (2006). Selling Sickness: How the World’s Biggest

Pharmaceutical Companies Are Turning Us All Into Patients. New

York: Nation Books.