Basic biochemical examination in endocrinologyulbld.lf1.cuni.cz/file/695/Basic biochemical...
Transcript of Basic biochemical examination in endocrinologyulbld.lf1.cuni.cz/file/695/Basic biochemical...
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Basic biochemical examination in endocrinology
Zdislava Vaníčková
2012
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Diabetes mellitus
Endocrinology of reproduction
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Endocrinology
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Hormones - definition
Hormones are endogenous substances produced by
specializeded cells
Secretion: continuous (thyroid hormones)
with diurnal rhythm (cortisol)
with monatial rhythm (menstrual cycle hormones)
seasonal rhythm (parathormon)
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Hormones - types
Proteohormones and peptides
Steroid hormones
Low molecular weight hormones derived from modified amino Low molecular weight hormones derived from modified amino
acids
Prostanoids
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Autocrine
Paracrine
Action of hormones
Endocrine
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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.lead to death without proper care.
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Langerhans islets
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B (beta) cells
70%
Produce insulin
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InsulinMen and other mammals
1 gen on chromosome 11
(rodents, 2 genes)
51 AA, 2 strands
Homology between species high:Homology between species high:
pig, dog, hare 1 AA; cow 3 AA; sheep, horse 4 AA.
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
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Insulin
C peptid
PREPROINSULIN
PROINSULIN
INSULIN
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Insulin
Daily production:
40-50 units
(15-20% of pancreatic depot)
50% basal secretion
50% postprandial secretion
Plasmatic halftime:
3-5 minutes, no transport protein
First-pass effect:
50% used during first passage through liver
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C peptid
Function unknown
Variable length
Used as marker of endogenous insulin production 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
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Insulin like growth factors
IGF-I
70 AMK
IGF-II
62 % homology (IGF-I and IGF-II)
50 % homology with insulin
More stimulate growth than insulinIGF-II
67 AMKMore stimulate growth than insulin
Have less metabolic effect than insulin
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A (alpha) cells
25%
Produce glucagon
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Glucagon29 amino acids
Synthetized as proglukagon
Plasmatic halftime 5 minutes
No transport protein
Inactivation in liver
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Glucagon
Enhances
glycogenolysis
lipolysis
gluconeogenesisgluconeogenesis
ketogenesis
Receptors mainly in liver
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D (delta) cells
5%
Produce somatostatin
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Somatostatin
cyclic 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, …
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Blood glucose regulation
- + INSULIN GLUCAGON
glucagon like peptid catecholamins
utilization in CNS glucocorticoides
muscle work growth hormone
FOOD INTAKE
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Blood glucose regulation
- + INSULIN GLUCAGON
glucagon like peptid catecholamins
utilization in CNS glucocorticoides
Muscle work growth hormone
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DM diagnosis
Fasting glycemia (venous and capillary blood)
<5,6 mmol/l no DM
5,7-7,0 mmol/l impaired fasting glycemia5,7-7,0 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)
DM diagnosis
Measurement at time 0 and 120 min (60 min and 180 min
sometimes added)
7.8
0 60 120
NORMAL
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OGTT
Impaired glucose tolerance
DM diagnosis
7.8
0 60 120
11.1
repeat OGTT
every 2-3 years
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OGTT
DM diagnosis
7.7
0 60 120
11.1
DM
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DM
Insulin
secretion glycemia
7.7
11.1
Insulin
sensitivity
secretion glycemia
8-10 years
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Lab tests in DM
BLOOD GLUCOSE
fasting
random
oral glucose tolerance test (OGTT)oral glucose tolerance test (OGTT)
glycemic profile
GLYCATED HAEMOGLOBIN, PEPTIDES, AGEs
INSULIN, C PEPTID, anti-GAD antibodies, antibodies against
insulin, antibodies against B cells (ICA, IA2)
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haemoglobin glycationHC=O HC=N-ß CH2-NH-ß
| | |
HCOH HCOH C=O
| | |
HOCH HOCH HOCH
ß-NH + | | |ß-NH2 + | | |
HCOH fast HCOH slow HCOH
| | |
HCOH HCOH HCOH
| | |
CH2OH CH2OH CH2OH
Aldimin Ketoamin
(labile HbA1c) (stabile HbA1c)
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Haemoglobin and derivates
Subunits present
sugar content
HbA0 α2ß2 - > 90%
HbA2 α2δ2 - 2%
HbF α2γ2 - 0.5%
Fructose-1,6-
Haemoglobin - types
HbA1a1 α2(ß-F-D-P)2 Fructose-1,6-diphosphate
<1%
HbA1a2 α2(ß-G-6-P)2 Glucose-6-phosphate
<1%
HbA1b ? ? <1%
HbA1c α2(ß-G)2 Glucose <4%
HbA1d ? ? traces
HbA1e ? ? traces
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DM compensation Values given by IFCC
Reference values 28 – 40 (95 % interval)
Haemoglobin A1c
DM compensation Values given by IFCC
applicable from 1. 1. 2004
excellent < 45
good 45 – 60
bad > 60
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Endocrinology of reproduction
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hypothalamus
pituitary gland
HRH-
-
pituitary gland
target organ
RH
H
-
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Female hormonal system
Gonadotropic hormones
FSH
LH
prolactin
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Gonadotropic hormones
FSH
Female hormonal system
function: follicles growth, stimulation of estrogens secretion
structure: proteohormon, 207 amino acids,
subunits alpha and beta
Lab assessment: immunoanalysis
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Gonadotropic hormones
LH
Female hormonal system
function: peak preceedes ovulation, afterwards
stimulation of both estrogen and gestagen
secretion
structure: proteohormon, 205 amino acids,
alpha and beta subunits
lab: immunoanalysis
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Gonadotropic hormones
prolaktin
Female hormonal system
function: mainly milk production, acts also on ovaries
structure: proteohormon, 198 amino acids, 1band
lab: immunoanalysis
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Native estrogens
structure: 18C steroids
Female hormonal system
aromatic A circle
lab: immunochemistry
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Native estrogens
Female hormonal system
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Native gestagens
structure: 21C steroids
Female hormonal system
Lab: immunochemistry
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Native gestagens
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