The Unified Field Theory of Diabetes, Clinical Chemistry, a - PowerPoint Presentation

Slide1

The Unified Field Theory of Diabetes, Clinical Chemistry, and Everything

By Chad

Guilliams

, M.

ED

., MLS(ASCP)

cmSlide2

Outline

Signs, Symptoms, Complications

Selling Sickness

Carbohydrates

Pancreas

Type I vs Type II Diabetes

Water/Osmolality/Electrolytes

Acid-Base Disorders

Lipids

Heart Disease

Renal DiseaseSlide3

http://memekid.com/funny-chemistry-cat-memes.htmSlide4

Signs, Symptoms, Complications

http://www.md-reasons.info/2014/07/diabetes-complications-of-diabetes.htmlSlide5

Selling SIckness

Ill Defined Diseases

Affect numerous people High Cholesterol and Diabetes

Drug Companies Profits

Expand boundaries of illness

New customers

Diabetes

Before 1997 Diabetes diagnosis fasting blood glucose > 140 mg/

dL

After 1997 Diabetes diagnosis fasting blood glucose > 126 mg/

dL

Cholesterol

Before 1998 High Cholesterol > 240 mg/dL After 1998 High Cholesterol > 200 mg/dL Increased new customers by 86%Lifestyle changesDiet and Exercise Slide6

Carbohydrates

Types of Energy the body can use

Carbohydrates

Proteins

Lipids

Carbs are Good

Carbohydrates

Glycemic index

Insulin Response

Definitions

Glycolysis

Glycogenesis

Glycogenolysis

Gluconeogenesis – ATP and Pyruvate

http://www.rogerspeakperformers.com/2012/the-glycemic-index/Slide7

pancreas

Anatomy of a Pancreas

Exocrine – digestive enzymes amylase and lipase

Increased in pancreatitis (lipase more specific)

Endocrine - Islets of Langerhans

Beta Cells – Insulin

Alpha Cells – Glucagon

Delta Cells – Somatostatin

Insulin

Allows glucose to enter cells

Only hormone than can decrease glucose

levelsGlucagonPrimary hormone responsible for elevating glucose levels

http://www.medicinenet.com/image-collection/pancreas_picture_1/picture.htmSlide8

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)

GlycogenolysisGlucagon acts by:A) Increasing glycogenolysisB) Increasing glycogenesisC) Increasing glycolysisD) Inhibiting glycogenolysisSlide9

Type I vs

type ii

Type I AKA insulin dependent diabetes (IDDM)

Mostly young and thin

Little 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

I

nsulin production issues

Diabetic ketoacidosis – rare

Hyperosmolar coma

Lab findings

Blood glucose levels >1000 mg/

dL

G

reatly increased osmolalitySlide10

http://www.psychiatrictimes.com/metabolic-disorders/metabolic-monitoring-patients-antipsychotic-medications/page/0/4Slide11

Monitoring diabetes

Glucose – serum, plasma, whole blood

Preferred diagnosis test is fasting plasma glucose (fasting 10 hours prior)

Reference range 70 -110

mg/

dL

Glycosylated hemoglobin or HbA1C – average glucose over 3 months

Whole 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=3Slide12

Carbohydrates Review

Jane Doe is a 55 year-old-female. Her lab results

were:

Fasting

glucose 122

mg/

dL

F

asting

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) KetoacidosisSlide13

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

A) Urine

microalbumin

B) Glucose tolerance testing

C) 2-hour postprandial serum glucose

D) Glycosylated hemoglobin

Carbohydrates ReviewSlide14

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)

Waterhttp://www.apswater.com/article.asp?id=129&title=What+are+the+chemical+properties+of+water?Slide15

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

]

/3Slide16

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-aldosterone

Stimulates sodium reabsorption

and potassium excretion

http://pixgood.com/adh-kidney.htmlSlide17

Water volume regulation

Water deficit

Osmolality increases (electrolytes concentrated)

Increased thirst

ADH is secreted

Increases water reabsorption

Aldosterone is inhibited

Less sodium reabsorbed = decrease in electrolytes

Water overload

Osmolality decreases (electrolytes diluted)

Thirst suppressed

Aldosterone secretedSodium is reabsorbed = increase in electrolytesSlide18

Electrolytes

Remember two basic types of dehydration

Dying of thirst in the desert – losing more water relative to electrolytes

Lab findings – all electrolytes elevated

Hypernatremia

Hyperosmolality

Vomiting and Diarrhea – losing more electrolytes relative to water

Lab findings – all electrolytes decreased

Hyponatremia

Hyposmololality

https://www.cartoonstock.com/directory/t/thirsty.aspSlide19

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 volume

Major extracellular

cation

135-145

mEq

/L

HyponatremiaWith low serum osmolality – diarrhea, vomiting, diureticsWith normal serum osmolality – in vitro hemolysisWith high serum osmolality – hyperglycemiaHypernatremiaDehydration, diabetes insipidus (dilute urine), hyperaldosteronismSlide20

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

HyperkalemiaHyperglycemia, hypoaldosteronism (Addison’s disease)Chloride – maintain electrical neutrality (chloride shift)Major extracellular anion 98-106 mmol/L

Passively follows sodium increased and decreased in the same conditions

Sweat chloride test for cystic fibrosis –

iontophoresis/pilocarpine

http://www.cdha.nshealth.ca/pathology-laboratory-medicine/clinical-chemistry/hemolysisSlide21

Electrolytes

Bicarbonate (HCO3-) – buffering system maintain pH

Second 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 acidosisIncreased  metabolic alkalosisExposure to air will decrease CO2Slide22

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

ElectrolytesSlide23

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

-

] + [HCO

3

-

])Slide24

Hyponatremia with a high osmolality is most commonly seen in

A) Diarrhea

B) Renal Failure

C) In

V

itro HemolysisD) Hyperglycemia

In dehydration which of the following hormones is responsible for increasing water reabsorption in the tubules

:

A)

Antiduretic

H

ormoneB) AldosteroneC) RenninD) ThyroxinWater ElectrolyteOsmolalityReviewSlide25

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

pCO

2

(35-45 mmHg)

HCO3 (22-26 mmol/L)Slide26

Acidosis or AlkalosisDetermine what is causing the problem

Respiratory or Metabolic (renal)

Respiratory problem

If pH and PCO2 are opposite each other

pH PCO2

pH PCO2

Metabolic problem

If pH and HCO3- go up together or down together

pH

HCO3-

pH HCO3-

Acid-Base DisordersSlide27

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 DisordersSlide28

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 DisordersSlide29

Lipids

Unsaturated Fat

3

Saturated Fat

Hydrogenation form of preservation

Trans Fat

Solid 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/Slide30

LipidsOrganic compounds insoluble in water

Fatty acids

Triglycerides

Cholesterol

Fatty Acids

Body makes most

Essential fatty acids -not made by the body

Omega 3 and Omega 6

Triglycerides

Majority of what we eat

Lots of calories

Cholesterol

Present in all cell membranes Building block of bile and steroid hormonesLiver makes most of what we needFat stored as Triglycerides in adipose tissueLipolysis – break down of fat for energy Ketone bodies

LipidsSlide31

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 cellsContains mostly cholesterolBAD cholesterol associated with Apoliprotein B

High levels of LDL and Apo B

risk

of heart diseaseHDLRemoves cholesterol out of cells

GOOD cholesterol associate with Apoliprotein AHigh levels of HDL and Apo A risk of heart disease

http://dolinabiotechnologiczna.pl/diagnostyka-laboratoryjna-2/ratunku-lipemia/

LipidsSlide32

Lipid review

Which of the following lipoproteins is the major carrier of cholesterol to peripheral tissues

?

A) VLDL

B) LDL

C) HDL

D) Chylomicrons

True or F

alse:

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/#.VT01CWN8MXkSlide33

Lipid panel includes (fasting 10-12 hours)

Total

cholesterol - measured

LDL – 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

diseaseSlide34

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, MDCK-MB (isoenzyme)– second most specific cardiac markerPeaks in 1 day returns to normal in 2 days Myoglobin – least specific markerSensitive rises within 1 hour returns to normal in 1 dayEarly indicatorNot included on subsequent cardiac panels only initial

http://dietchoices.com/diet-plans/heart-attack-grill-diet/Slide35

Heart disease review

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

?

A)

hs

-CRP

B) Troponin I

C) BNP

D) Total CKSlide36

Other Cardiac Markers

hsCRP

– high sensitivity C-reactive protein

Measures inflammation related to stress (cortisol)

Increased

hsCRP

= increased plaque

formation

BNP – B natriuretic peptide

Increased in CHFSlide37

Renal System

Elimination of waste

Urea

Protein

degradation = ammonia =

urea

Creatinine

Waste product of

creatine

Jaffe reaction

Ketones positive

interference

Falsely elevate creatinine levelsUric Acid

Final product of purine metabolism

Monosodium

urate crystals synovial fluid = gout

Polarized microscopeGlomerular Filtration Rate24 hour urine Creatinine Clearance

U

x

V

x

1.73

S 24V SA

Creatinine

Clearance =Slide38

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 Failure

Serum

High

levels of BUN and Creatinine

Urine Dilute low specific gravityLow in BUN and CreatinineHigh in proteinMicroalbuminuria – early indicator diabetic nephropathy

Renal failure will result if diabetes is not well managed

http://www.rayur.com/acute-renal-failure.htmlSlide39

Case studySlide40

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.