selected topics in biochemistry: bone, endotheliumium adn adipose tissue
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Selected Topics in Biochemistry: Bone, Endotheliumium adn Adipose Tissue. František Duška. Biochemistry of Bone. Case Mechanism of Bone Remodeling Calcium and Phosphate Biochemical Markers of Bone Metabolism. Function of Bone. Mechanical lever for musscles protects bone marrow - PowerPoint PPT PresentationTRANSCRIPT
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Selected Topics in Biochemistry: Bone, Endotheliumium adn Adipose Tissue
František Duška
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1. Case2. Mechanism of Bone Remodeling3. Calcium and Phosphate4. Biochemical Markers of Bone Metabolism
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Function of Bone
•Mechanical▫lever for musscles▫protects bone marrow
•Calcium and phosphate store (cca 1kg) ▫influences their metabolism
•Buffer▫long lasting MAC (renal failure etc.)
releases phosphate and bicarbonate▫contributes to ABB stability, even at the
price of bone damage
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Case No. 1
•Current problem: female, 59 yrs, strong pain at right groin after a minor fall
•History: no serious diseases, no medication, only analgesics for backache (worsen for 3 yrs). Climacterium at 44, no HRT
•Works as officer, no abuse
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Case No. 1
•On examination: BP 150/90, HR 100/min, Breaths 20/min, supine: right leg shortened, in abduction and external rotation, tenderness oevr major trochanter, passive movement of right hip painful
•Othervise normal physical examination
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Case No. 1
•Dg: Comminutive intertrochanteric fracture of right hip after minor trauma, osteoporosis
•After hip replacement (CCEP) transferred for examination and tratment of osteoporosis
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Bone composition:
•Cells:▫synthetizing new bone: osteoblasts,
osteocytes▫beaking down old bone: osteoclasts
•Intercellular matrix:▫organic: collagen type I + non-collagenní
proteins (e.g. osteocalcin)▫inorganic: hydroxyapatite: Ca10(PO4)6(OH)2
•Terms: lamelar/trabecular bone
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Bone aand metabolism of Ca2+
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Faktory ovlivňující mtb. bonei• PTH: zvyšuje resorpci i
syntézu: výsledek = zvýšené uvolňování Ca2+
• kalcitonin: inhibuje osteoklasty, snižuje resorpci bonei: výsledek = zvýšené ukládání Ca2+ do bonei
• estrogeny: dtto• IGF-1: zodp. za růst boneí • kalcitriol: zajišťuje
dostupnost Ca2+ pro bone• glukokortikoidy: snižují
novotvorbu bonei
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Laboratory markers of bone metabolism
•S-Ca2+
▫total 2,25-2,75 mM▫ionized: 50%, i.e. 1.3 mM
•S-phosphate▫appr. 1mM
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Laboratory markers of bone metabolismMarkers of bone synthesis Markers of bone degradation
• S-ALP bone izoenzyme• U-terminal propeptids of
collagen type I• S-osteocalcin
• S-ACP bone izoenzyem (tartate resistant)
• U-karboxytermina telopeptide of collagen
• U-hydroxyproline• U-deoxypyridinoline• Ca2+ urine waste/24 hrs
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Collagen I
NH2
COOH
karboxyterminální propeptid procollagenu (PICP)
ŠTĚPENÍ PŘI SYNTÉZE collagenU
STĚPENÍ PŘI DEGTADACI collagenU
karboxyterminální telopeptid collagenu
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Common bone disorders
•Osteoporosis = loss of both inorganic and organic bone matrixfractures▫primary = cause is complex and unknown▫secondary= cause identifiable
•Osteomalacia (adult)/rachitis (childhood) = loss of inorganic bone mass bone softening, deformities▫typical cause: lack of vit. D
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Case No. 1Lab. value comment
S-Ca2+ =2.2 mM
S-P =1,12 mM normal
S-ALP = 24 IU (norma 10-22 IU)
S-ACP = 31 ug/ml (norma=7-28)
S-PTH274 ng/l (20-300 ng/l) normal
Densitometry: bone density -2.1 SDElfo of plasma proteins : normal
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Case No. 1
•Conclusion: primary osteoporosis, type II, „fast-looser“
•Therapy: vit D 600IU/day, Ca-effercescens 1g/day, palmidronate (bone resorption inhibitor)
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Conclusion: bone metabolism
•What are functions of a bone?•What a bone consists of? Which
compounds can be used diagnostically?•Which hormones regulate plasma Ca2+?•Which routinelly assayed lab values can
point out to bone disorder?
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1. Endotheliumium function2. Case
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Endothelium
•= epithelium of inner vessel wall layer•1013 cells (1 kg!!!)•Functions:
▫anticoagulant (unwettable)▫barrier (zonulae adherentes)▫regulates vascular tonus microcirculation
macrocirculation▫metabolic: HRHL, LPL
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Endothelium activation
•non-specific reaction (triggered by physical forces, infection, inflammation)
•Endothelium becomes: ▫pro-coagulant (maintaining vascular bed
integrity)▫pro-inflammatory (immune response) ▫permeable (WBC diapedesis)
•Whilst usually beneficial, it may be harmfull or life-threatening if generalized and uncontrolled..
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Case No. 2•male, 41 yrs, with known peanuts allergy,
accidentally ingested nougat. After 2 min suffered paresthesia of tongue and lips. Emergency service called for increasing dyspnea.
•On addmission: ▫alert, agitatetd, dyspnea, sat 99% on O2 by
facemask, bilat. wheezes on auscultation, BP 90/40, HR 135/min, Quincke edema of lips and tongue, diffuse urtica on whole body surface
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Case No. 2
•Dg: anaphylactic reaction due to exposure to peanuts
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Case No. 2
•Alergická reakce vede ke generalizované aktivaci Endotheliumu:
•Vyšší permeabilita způsobí1. otok kůže a sliznickopřivka, Quinckeho
edém 2. otok dýchacích cest
bronchiokonstrikce, dušnost3. únik tekutiny z cév hypovolémie
•Vasodilatace hypotenze, šok
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Case No. 2
•Therapy:▫i.v. line put during transport, hydrocortison
+ epinephrinei.v., volumexpansion R1/1▫vital function stable during transport
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Case No. 2
•Therapy:▫admitted and observed in ICU, vital
function monitoring with the plan to intubate in case of worsening
▫corticoids, antihistaminics (H1 blockers)
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Case No. 2
•In-hospital course: ▫rapidly improving after admission▫ after 60 mins BP 140/80 without support,
HR 78/min, no wheezing above both lungs, urtica unchanged
▫next day morning (10hrs after arrival): no subjective complaints, discharged, alergology examination recommended on out-hospital basis
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Endothelium - závěr
•List endothelium functions.
•Describe endothelium-mediated vasodilation.
•What is edothelium activation?
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1. Storage function: lipolysis and lipogenesis2. Endocrine and regulatory function3. Case
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Adipose Tissue: function I•TAG storage (postprandial)
▫lipoprotein lipase (endothelial) activated by insulin stores TAG ingested or synthesized in the liver
▫de novo lipogenesis: from glucose•Lipolysis = release of NEFA + glycerole
(fasting)▫Hormone-sensitive lipase (IC)
inhibited by insulin activators: sympathetic NS, GH, (glucagon)
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Adipose Tissue: function II.
•Endokrinní function: ▫leptin = signál o stavu tukových zásob
anorexigenní působení 167 AK, ob gen
▫adiponectin▫TNF-alfa▫rezistin
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Brown Adipose Tissue
•in human only in newborns•hibernating mammals•many fatty inclusions, many mitochondria•rich adrenergic inervation•thermogenin = UCP-1 creates heat
instead ATP
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Case No. 3.•Farooqi et al., N Engl J Med, 1999•Female child 8,5 yrs. Pakistani origin, parents
= brother and sister-in-law•Current problem:morbid obesity, hyperfagia
▫ nowadays 94,4 kg (above 99,9 percentile), 140 cm
•History:▫ normal birth weight, BW increases from 4
months▫ at the age of 6 liposuccion as an attempt to
improve mobility
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Case No. 3
•Investigation reveals unmesurable level of plasma leptin. Cause: frameshift mutation in ob-gene
•12 trial of s.c. leptin therapy begun in 1998
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Case No. 3
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Case No. 3
•After 12 months of therapy:
▫weight loss 17 kg (out of which 16,1 kg fat and 0,9 kg of lean body mass)
▫mobility improved
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