Fluoride metabolism

Importance

CariespreventionCariesprevention

Haemopoesis

Reproduction

Hard tissue

Mineralisation

•

Most important sources:

–

food–

water

–

air

Supplementary

sourcesMilk

Salt

Fluoridemetabolism

•

Absorption•

Distribution

•

Storage•

Excretion/elimination

„ADME”

Absorption•

GI tract–

Oral

mucosa

(toothpaste, mouth

water…)

•

5-8% absorbed, concentration

important

–

GI tract:•

Passive

transport

of

HF (gastric

juice

H+)

–

Depending

on

physico-chemical

features:•

solvability

(NaF

CaF2

, AlF3

)

Milk, calcium lowers the absorption!

fasting

with milk

after a calcium rich breakfast

Plas

ma

fluor

ide

cc. (μm

ol/l)

Hours

bone surface

blood vessel

Readily excangable fluorid

BoneDentine

Enamel

Fluoride content of different hard tissues

before fluoride after fluoride

a, c : healty enamel

b: caries

Caries and fuoride treatment

Plasma and saliva fluoride levels

A fluoridreabsorption pH dependent

acidic urine

Alkalic urine

Acidic urine

BLOOD

Fluoride elimination

Fluoride balance

•

Measuring

fluoride

intake

and

excretion–

Absorption

< excretion

negative

•

example: childhood–

Absorption

> excretion

positive

–

Absorption

= excretion

Acute toxicity• Probably toxic dose: ~5mg/kg somewhere

1-10mg• Estimated lethal dose: 32-64mg/kg

– Pl. Elmex gel (highest fluoride content – registered as drug!!) 12,5 mg/g fluorid (12.500 ppm!) (25 és 125 g)

– Pl. Parodontax fluoride – 1400 ppm

• Symptoms from lower doses!– as low as 0.3 mg/kg (Gessner, 1994)

(http://content.nejm.org/cgi/content/full/330/2/95)

How much is toxic from these for a 12 kg child?

• Once absorbed, fluoride binds calcium ions and may lead to hypocalcemia. Fluoride has direct cytotoxic effects and interferes with a number of enzyme systems; it disrupts oxidative phosphorylation, glycolysis, coagulation, and neurotransmission (by binding calcium). Fluoride inhibits Na+/K+ -ATPase, which may lead to hyperkalemia by extracellular release of potassium. Fluoride inhibits acetylcholinesterase, which may be partly responsible for hypersalivation, vomiting, and diarrhea (cholinergic signs). Seizures may result from both hypomagnesemia and hypocalcemia. Severe fluoride toxicity will result in multiorgan failure. Central vasomotor depression as well as direct cardiotoxicity also may occur. Death usually results from respiratory paralysis, dysrhythmia, or cardiac failure.

• Severity of symptoms depends upon the amount of fluoride ingested. These include abdominal pain, diarrhea, dysphagia, hypersalivation, , nausea, vomiting. Electrolyte abnormalities including hyperkalemia, hypocalcemia, hypoglycemia, and hypomagnesemia may occur. Neurological symptoms include headache, muscle weakness, hyperactive reflexes, muscular spasms, paresthesia seizures, tetanic contractions, and tremors. In severe cases, multiorgan failure will occur. Death typically results from cardiac arrest, shock, widening of QRS, and various arrhythmias occur.

http://emedicine.medscape.com/article/767546-overviewhttp://emedicine.medscape.com/article/767260-overviewhttp://en.wikipedia.org/wiki/Abdominal_painhttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Dysphagiahttp://en.wikipedia.org/wiki/Hypersalivationhttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Electrolytehttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Hypocalcemiahttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Hypomagnesemiahttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Muscle_weaknesshttp://en.wikipedia.org/wiki/Spasmhttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Seizureshttp://en.wikipedia.org/wiki/Tetanic_contractionhttp://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Cardiac_arresthttp://en.wikipedia.org/wiki/Cardiac_arresthttp://en.wikipedia.org/wiki/Shock_(circulatory)http://en.wikipedia.org/wiki/Electrical_conduction_system_of_the_hearthttp://en.wikipedia.org/wiki/Arrhythmia

Hard tissue

Goal

• Patomechanism of caries

• Diagnosis of caries

Quantitative Light-induced Fluorescence

• Based on the autofluorescence of the teeth• High energy blue light emission in green• proportional of mieralisation

• Physical– structure

• Chemical– organic – anorganic components– acid solvability

• Other

Properties

Physical

• Hardness – Vickers hardness

• Cristall structure – X-ray diffraction

• Mineralisation, distribution – μCT

ChemischStep 1: pulverisation

Step 2: resuspending in bromoform-aceton mix

Separation of dentin and enamel with centrifugation

Step 3: centrifugation

Step 4: wash with aceton and dry

Solvability in acid

• measuring demineralisation– standardisation:

• acid cc.• time• surface area

– measuring Ca2+ cc.

Importance: GERD

acid proof lack

free enamel surface

Vickers hardness

rat upper incisors

protein poor food109261326

normal food129320398

Dentindeepenamel

surface enamel

diamond

enamel surface

impression on the surface

SkyScan-1172 High-resolution desk-top micro-CT systemX-ray detector: 1.3 Megapixel (1280x1024) 12-bit digital CCD-camera,Maximum object size for scanning and reconstruction: 20-37 mmComputer for 3D-reconstruction and image analysis: Dual Intel Xeon 3.6 GHz,2GB RAM, internal Writer, 320GB HDD, 128MB graphical cardReconstruction time: 0.42-1.1 sec per cross sectionReconstruction algorithms: Cone-beam volumetric reconstruction (Feldkamp)

Fluoride metabolismImportanceSlide Number 3Slide Number 4FluoridemetabolismAbsorption�Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Fluoride balanceAcute toxicitySlide Number 18Hard tissueGoalQuantitative Light-induced Fluorescence Slide Number 22Slide Number 23PhysicalChemischSolvability in acidSlide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31