basic biochemical examination endocrinology in ...ukb.lf1.cuni.cz/ppt/bio_exam.pdf · diabetes...

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Basic biochemical examination in endocrinology

Zdislava Vaníčková

2005/06

Diabetes mellitus

Endocrinology of reproduction

Endocrinology

Hormones - definitionHormoness are endogenous substances produced by specializeded cells

Secretion: continuous (thyroid hormones)with diurnal rhythm (cortisol)with monatial rhythm (menstrual cycle)seasonal rhythm

Hormones - typesProteohormones and peptides

Steroid hormones

Low molecular weight hormones derived from modified amino acids

Prostanoids

Autocrine

Paracrine

Endocrine

(Neurocrine)

Action of hormones

hypothalamus

pituitary gland

target organ

HRH

RH

H

-

-

-

Endocrinopathies

States hyperfunctionhypofunctiondysfunction

Diseases primar (periferal)secundar (central)

Diabetes mellitus

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DM definitionWHO 1985

Status characterized by chronic elevation of blood glucose, that could be connected with clinical syndromes and could lead to death without proper care.

Langerhans islets B (beta) cells

70%Produce insulin

InsulinMen and other mammals1 gen on chromosome 11

(rodents, 2 genes)

51 AMK, 2 strands

Homology between species high:pig, dog, hare 1 AMK; cow 3 AMK; sheep, horse 4 AMK.

Secretion increased: elevation of blood sugar, aminoacids, parasympaticus system action, glukagon, glucocorticoides, growth hormone, placental lactogen,estrogenes, gestagenes (during pregnancy)Secretion decreased: fats, sympaticus action, somatostatin, adrenalin

Insulin

C peptid

PREPROINSULIN

PROINSULIN

INSULIN

Insulin

dE

Daily production:40-50 units(15-20% of pancreatic depot)50% basal secretion50% postprandial secretion

Plasmatic halftime:3-5 minutes, no transport protein

First-pass effect:50% used during firs passage through liver

C peptidFunction unknown

Variable lengths

Used as marker of endogenous insulin production (produced in equimolar proportion, can be used in patients on insulin therapy as well)

No first-pass effect

Insulin like growth factors

IGF-I70 AMK

IGF-II67 AMK

62 % homology (IGF-I and IGF-II)50 % homology with insulin

More stimulate growth than insulinHave less metabolic effect than insulin

A (alpha) cells25%Produce glucagon

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Glucagon29 amino acids

Synthetized as proglukagon

Plasmatic halftime 5 minutes

No transport protein

Inactivation in liver

Glucagon

Enhances

glycogenolysislipolysisgluuconeogenesisketogenesis

Receptors mainly in liver

D (delta) cells5%Produce somatostatin

Somatostatincyclic peptide, 14 amino acids

in CNS – neurotransmitter function

synthesized also in other places in GIT

Inhibition of insulin and glucagon secretion

Slowers gastric emptying, lowers gastrin secretion, pancreatic exocrine secretion, …

F cellsRare

Produce pancreatic polypeptid

Peptid, 36 amino acids

Unknown function

Other hormonesTRH

Beta-endorfin

CRH-like peptid

Pancreastatin

Blood glucose regulation

- + INSULIN GLUCAGONglucagon like peptid catecholaminsutilization in CNS glucocorticoidesMuscle work growth hormone

Blood glucose regulation

- + INSULIN GLUCAGONglucagon like peptide catecholaminsutilization in CNS glucocorticoidesMuscle work growth hormon

FOOD INTAKE

DM diagnosisFasting glycemia (venous and capillary blood)

<6 mmol/l no DM6,1-7,0 mmol/l impaired fasting glycemia>7 mmol/l DM present

Glycemia in random sample

Several times >10mmol/l DM present

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OGTT (oral glucose tolerance test)

75 g of glucose in 400 ml water (tea)

Measurement at time 0 and 120 min (60 min and 180 min sometimes added)

6,7

0 60 120

NORMAL

DM diagnosis

6,7

0 60 120

10

repeat OGTTevery 2-3 years

OGTT

Impaired glucose tolerance

DM diagnosis

6,7

0 60 120

10

DM

OGTT

DM diagnosis

DM

6,7

10

Insulinsensitivity

Insulinsecretion glycemia

8-10 years

Hypoglycemia3,5 mmol/l

3,3 mmol/l contra regulation starts

higher katecholamines, corticoids, glukagon, thyroidal hormones, growth hormon

first clinical signs

2,8 mmol/l neuroglycopenia

Hypoglycemic coma

Hyperglycemic coma

Lab: haemoconcentration hyperglycemia ketonemia metabolic acidosis and hypokalemia

Hyperosmolar comaLab: hyperglycaemia

hyperosmolarity

Lab tests in DM

BLOOD GLUCOSEfastingrandomoral glucose tolerance test (OGTT)glycemic profile

GLYCATED HAEMOGLOBIN, PEPTIDES, AGEs

INSULIN, C PEPTID, anti-GAD antibodies, antibodies againstinsulin, antibodies against B cells

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Reference values < 3,8 mmol/l hypoglycemia> 7,8 mmol/l hyperglycemia

Glucose haemoglobin glycationHC=O HC=N-ß CH2-NH-ß| | |

HCOH HCOH C=O| | |

HOCH HOCH HOCHß-NH2 + | | |

HCOH rychle HCOH pomalu HCOH| | |

HCOH HCOH HCOH| | |CH2OH CH2OH CH2OH

Aldimin Ketoamin(labile HbA1c) (stabile HbA1c)

Haemoglobin and derivates

Subunits present sugar content

HbA0 α2ß2 - > 90% HbA2 α2δ2 - 2%

HbF α2γ2 - 0.5%

HbA1a1 α2(ß-F-D-P)2 Fructose-1,6-diphosphate <1%

HbA1a2 α2(ß-G-6-P)2 Glucoss-6-phosphate

<1%

HbA1b ? ? <1% HbA1c α2(ß-G)2 Glucose <4% HbA1d ? ? traces HbA1e ? ? traces

Haemoglobin - types

> 6,0 % bad

4,5 – 6,0 % good

< 4,5 % excellent

Values given by IFCC applicable from 1. 1. 2004 DM compensation

Reference values 2,8 – 4,0 % (95 % interval)

Haemoglobin A1c Nonenzymatic bond of glucose to proteins in tissues (collagen…) and DNA

AGE = advanced glycation end products

AGEs

Endocrinology of reproduction

Female hormonal system

Gonadotropic hormones

FSH

LH

prolactin


FSH

function: follicles growth, stimulation of estrogens secretion

structure: proteohormon, 207 amino acids, subunits alpha a beta

Lab assessment: RIA, EIA



LH

function: peak precedes ovulation, afterwards stimulation of both estrogen and gestagen secretion

structure: proteohormon, 205 amino acids, alpha and beta subunits

lab: immunochemistry


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prolaktin

function: mainly milk production, acts also on ovaries

structure: proteohormon, 198 amino acids, 1band



Native estrogens

structure: 18C steroidsaromatic A circle



Native estrogens


Native gestagens

structure: 21C steroids

Lab: immunochemistry


Native gestagens


Androgens

female: ovary and suprarenals(male: testes and suprarenals)

Structure: 19C steroids

testosteronandrostendiondehydroepiandrostendion


Menstrual cyclePregnancy

EPF – early pregnancy factor

Produced by the ovary gland

First pregnancy marker, 48 hours

Immunosuppressive

No routine method

Female hormonal system -pregnancy

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hCG

Glycoprotein, 2 subunits: alpha (92) and beta (145)

detectable 8-11 day

Concentration doubles every two days



Weeks of pregnancy

HPL – human placental lactogen

Polypeptid, 191 amino acids


Weeks of pregnancy

PAPP A-D pregnancy associated plasma proteins

SP1 pregnancy specific protein

Female hormonal system -pregnancy Infertility

15-20% couples

Causes female 50%male 40%unclear 10%

Start testing after 12 (18) months

examinationmale: Spermiogram, (androgens)

female:Sonography several times in one menstrual cycle

Lab: FSH any time

(hypo- resp. hypergonadotropic status)

LH 3-5 day of cyclebasal secretion

Lab (cont.):

Estradiol older marker, useful without sono

Progesteron middle of the luteal phase

Prolactin 3-5 dayhyperprolactinemia leads to anovulation

examination Hyperandrogenic syndrome= HAS, syndrome of polycystic ovaries

Most common endocrinopathy in fertile age women

17-33 % women

Basic criterion: increased androgens level

Ethiology not known

Familial

Examination:

Androgens

Gonadotropins (LH and FSH, LH/FSH ratio)

SHBG

Hyperandrogenic syndrome

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LiteratureBureš: Základy vnitřního lékařství, Galén, 2003

Harperova biochemie, HaH, 2002

Cibula: Základy gynekologické endokrinologie, Grada, 2002

Stárka: Endokrinologie, Maxdorf, 1997

Rabe: Memorix – Gynekologie, Scientia Medica, 1993

basic biochemical examination endocrinology in ...ukb.lf1.cuni.cz/ppt/bio_exam.pdf · diabetes...

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