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BRAIN METABOLISMPresented by S Aryo No
High energy requirements (~10 mgkgmin)
Low energy reserves
The energy is needed to maintain the ionic gradient across nerve membranes
Tinggi energi persyaratan (~ 10 mg kg menit)
Rendah energi cadangan
Energi yang diperlukan untuk menjaga gradien ion melintasi membran saraf
Brain Metabolism
Energy metabolism of the brain 2 of body weight 20 of energy expenditure
GLUCOSE is the main fuel daily consumption 120g adopted starvation (3 weeks) oxidation of ketones
in the brain covers up to 50 of energy 2 dari berat badan 20 dari pengeluaran energi
GLUKOSA adalah bahan bakar utamaharian konsumsi 120Gkelaparan diadopsi (3 minggu) oksidasi keton di otak mencakup hingga 50 energi
Oxygen uptake Brain 20 of whole-body O2 consumption The most vulnerable to hypoxia
5 min of Ventrikel Fibrilationarrest may lead to irreversible brain damage
temperature dependent Otak 20 dari seluruh tubuh konsumsi O2
Yang paling rentan terhadap hipoksia5 menit dari Fibrilation ventrikel penangkapan dapat menyebabkan kerusakan otak ireversibeltergantung suhu
Oxidation of non-glucose substrates ketoneslactate during prolonged fasting not in everyday life
Glucose oxidation provides more than 90 of the energy needed
Brain function almost totally dependent on a continuous supply of glucose from the arterial circulation
Oksidasi non-glukosa substrat keton laktat selama puasa yang berkepanjangan bukan dalam kehidupan sehari-hariGlukosa oksidasi menyediakan lebih dari 90 dari energi yang dibutuhkanOtak hampir sepenuhnya tergantung pada kelangsungan penyediaan glukosa dari sirkulasi arteri fungsi
The source of Brain Metabolism
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
High energy requirements (~10 mgkgmin)
Low energy reserves
The energy is needed to maintain the ionic gradient across nerve membranes
Tinggi energi persyaratan (~ 10 mg kg menit)
Rendah energi cadangan
Energi yang diperlukan untuk menjaga gradien ion melintasi membran saraf
Brain Metabolism
Energy metabolism of the brain 2 of body weight 20 of energy expenditure
GLUCOSE is the main fuel daily consumption 120g adopted starvation (3 weeks) oxidation of ketones
in the brain covers up to 50 of energy 2 dari berat badan 20 dari pengeluaran energi
GLUKOSA adalah bahan bakar utamaharian konsumsi 120Gkelaparan diadopsi (3 minggu) oksidasi keton di otak mencakup hingga 50 energi
Oxygen uptake Brain 20 of whole-body O2 consumption The most vulnerable to hypoxia
5 min of Ventrikel Fibrilationarrest may lead to irreversible brain damage
temperature dependent Otak 20 dari seluruh tubuh konsumsi O2
Yang paling rentan terhadap hipoksia5 menit dari Fibrilation ventrikel penangkapan dapat menyebabkan kerusakan otak ireversibeltergantung suhu
Oxidation of non-glucose substrates ketoneslactate during prolonged fasting not in everyday life
Glucose oxidation provides more than 90 of the energy needed
Brain function almost totally dependent on a continuous supply of glucose from the arterial circulation
Oksidasi non-glukosa substrat keton laktat selama puasa yang berkepanjangan bukan dalam kehidupan sehari-hariGlukosa oksidasi menyediakan lebih dari 90 dari energi yang dibutuhkanOtak hampir sepenuhnya tergantung pada kelangsungan penyediaan glukosa dari sirkulasi arteri fungsi
The source of Brain Metabolism
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Energy metabolism of the brain 2 of body weight 20 of energy expenditure
GLUCOSE is the main fuel daily consumption 120g adopted starvation (3 weeks) oxidation of ketones
in the brain covers up to 50 of energy 2 dari berat badan 20 dari pengeluaran energi
GLUKOSA adalah bahan bakar utamaharian konsumsi 120Gkelaparan diadopsi (3 minggu) oksidasi keton di otak mencakup hingga 50 energi
Oxygen uptake Brain 20 of whole-body O2 consumption The most vulnerable to hypoxia
5 min of Ventrikel Fibrilationarrest may lead to irreversible brain damage
temperature dependent Otak 20 dari seluruh tubuh konsumsi O2
Yang paling rentan terhadap hipoksia5 menit dari Fibrilation ventrikel penangkapan dapat menyebabkan kerusakan otak ireversibeltergantung suhu
Oxidation of non-glucose substrates ketoneslactate during prolonged fasting not in everyday life
Glucose oxidation provides more than 90 of the energy needed
Brain function almost totally dependent on a continuous supply of glucose from the arterial circulation
Oksidasi non-glukosa substrat keton laktat selama puasa yang berkepanjangan bukan dalam kehidupan sehari-hariGlukosa oksidasi menyediakan lebih dari 90 dari energi yang dibutuhkanOtak hampir sepenuhnya tergantung pada kelangsungan penyediaan glukosa dari sirkulasi arteri fungsi
The source of Brain Metabolism
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Oxygen uptake Brain 20 of whole-body O2 consumption The most vulnerable to hypoxia
5 min of Ventrikel Fibrilationarrest may lead to irreversible brain damage
temperature dependent Otak 20 dari seluruh tubuh konsumsi O2
Yang paling rentan terhadap hipoksia5 menit dari Fibrilation ventrikel penangkapan dapat menyebabkan kerusakan otak ireversibeltergantung suhu
Oxidation of non-glucose substrates ketoneslactate during prolonged fasting not in everyday life
Glucose oxidation provides more than 90 of the energy needed
Brain function almost totally dependent on a continuous supply of glucose from the arterial circulation
Oksidasi non-glukosa substrat keton laktat selama puasa yang berkepanjangan bukan dalam kehidupan sehari-hariGlukosa oksidasi menyediakan lebih dari 90 dari energi yang dibutuhkanOtak hampir sepenuhnya tergantung pada kelangsungan penyediaan glukosa dari sirkulasi arteri fungsi
The source of Brain Metabolism
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Oxidation of non-glucose substrates ketoneslactate during prolonged fasting not in everyday life
Glucose oxidation provides more than 90 of the energy needed
Brain function almost totally dependent on a continuous supply of glucose from the arterial circulation
Oksidasi non-glukosa substrat keton laktat selama puasa yang berkepanjangan bukan dalam kehidupan sehari-hariGlukosa oksidasi menyediakan lebih dari 90 dari energi yang dibutuhkanOtak hampir sepenuhnya tergantung pada kelangsungan penyediaan glukosa dari sirkulasi arteri fungsi
The source of Brain Metabolism
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Insulin independent GLUT1 (55 kd form)
localized in microvessels of the blood-brain barrier Moves glucose from the capillary lumen to the brain interstitium
GLUT3 GLUT1 (45 kd form)
transport glucose from interstitium into neurons and glial cells
Upregulation in chronically hypoglycemic rats independen insulin
GLUT1 (55 kd form)terlokalisasi di microvessels dari penghalang darah-otak Memindahkan glukosa dari lumen kapiler ke interstitium otakGLUT3 GLUT1 (45 kd form)mengangkut glukosa dari interstitium menjadi neuron dan sel glialUpregulation di kronis tikus hipoglikemik
Transport of Glucose
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Glycogen---stored exclusively in glial cells (astrocytes) Metabolize to lactate that can be taken up and used as fuel by neurons
Low content in brain (~3 mmolkg) Unable to sustain brain metabolism for more than 4 to 5 minutes
Glikogen --- disimpan secara eksklusif dalam sel glial (astrosit) Memetabolisme menjadi laktat yang dapat diambil dan digunakan sebagai bahan bakar oleh neuron
Rendah konten dalam otak (~ 3 mmol kg) Tidak dapat mempertahankan metabolisme otak selama lebih dari 4 sampai 5 menit
Brain Metabolism
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
1048708What the brain does with protein DNA RNA synthesis and maintenance Neurotransmitter production (synaptic efficacy) Growth factor synthesis Structural proteins
Neurite extension (axons dendrites) Synapse formation (connectivity)
1048708What the brain does with fat Cell membrane integrity Synapse formation Myelin formation 1048708 Apa otak lakukan dengan protein
DNA RNA sintesis dan pemeliharaanNeurotransmitter produksi (efikasi sinaptik)Faktor pertumbuhan sintesisstruktural proteinNeurite ekstensi (akson dendrit)Synapse pembentukan (konektivitas)
1048708 Apa otak lakukan dengan lemakIntegritas membran selSynapse pembentukanmyelin pembentukan
Protein and fat in the brain
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Meski glukosa penting bagi otak namun kadarnya hanya sedikit
Asam amino jumlahnya 6-8 kali lbh banyak di banding di dalam darah
Asam amino asam di otak lebih banyak (aspartat dan glutamat 300x lbh banyak dibanding dg di plasma)
Kemampuan otak untuk menyimpan dan menggunakan nitrogen sangat rendah shg laju ambilan AA dari darah sangat rendah
Konsentrasi AA intrasel dlm otak tinggi (glutamat aspartat GABA) menunjukkan metabolisme AA cukup aktif
Protein metabolism
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Otak mengandung lipid sederhana dan kompleks yg berfungsi untuk mempertahankan integritas membran drpd sbg senyawa metabolik
Lipid terletak pd sel dan membran sel Turn over lipid di otak rendah Kolesterol serebrosida fosfatidiletanolamin
dan sfingomielin dimetabolisme secara lambat di otak
Lipid metabolism
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Liver--predominant site of glucose production Kidney--contributes minimally After 60 hours of fasting kidney contributes significantly more (~25)
through gluconeogenesis The contribution of the kidney to glucose homeostasis are consistent with
the observation of hypoglycemia in some patients with chronic renal insufficiency
Hati - situs utama produksi glukosaGinjal - menyumbang minimalSetelah 60 jam puasa ginjal memberikan kontribusi signifikan lebih (~ 25) melalui glukoneogenesisKontribusi dari ginjal untuk homeostasis glukosa konsisten dengan pengamatan dari hipoglikemia pada beberapa pasien dengan insufisiensi ginjal kronis
Organs release glucose
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Hypoglycemia plasma glucose concentration below 50 mgdL 76 -72 mgdL1048708 suppression of insulin secretion ~67 mgdL1048708 counterregulatory hormones Conservative definition plasma glucose lt75 mgdL Important to establish the lower limit of plasma glucose in intensive therapy to
prevent recurrent hypoglycemia and hypoglycemia unawareness Hipoglikemia glukosa plasma konsentrasi di bawah 50 mg dL
76 -72 mg dL 1048708 penekanan sekresi insulin~ 67 mg dL 1048708 hormon counterregulatoryDefinisi konservatif glukosa plasma lt75 mg dLPenting untuk menetapkan batas bawah glukosa plasma dalam terapi intensif untuk mencegah hipoglikemia berulang dan ketidaksadaran hipoglikemia
Hypoglycemia
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Brain1048708 key organ for sensing hypolgycemia ldquoventromedial hypothalamusrdquo acts as a glucose sensor triggers counterregulation
Liver1048708 senses glucose concentration in the absence of counterregulatory hormones
Otak 1048708 organ kunci untuk merasakan hypolgycemia Ventromedial hipotalamus bertindak sebagai sensor glukosa memicu counterregulation
Hati 1048708 indra konsentrasi glukosa dalam ketiadaan hormon counterregulatory
Hypoglycemia Sensors
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Hypoglycemia1048708 ventromedial hypothalamus 1048708 suppression of insulin 1048708 increase counterregulatory hormone (glucagon epinephrine1048708 growth hormonecortisol)
Hipoglikemia 1048708 hipotalamus ventromedial 1048708 penekanan insulin 1048708 peningkatan counterregulatory hormon (glukagon epinefrin 1048708 hormon pertumbuhan kortisol)
Architecture of Counterregulatory System
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Whatacutes the first thing that happens when you think Excitatory firing Glu uptake by glia Na+ influx ATP
consumption by Na-K-ATPase activation of glycolysis lactate transported to neurons
Local increase in lactate increases blood flow
Excitotoxity = excesive Glu release epilepsy traumatic brain injury Na+ and Ca2+ intra cell accumulation swelling Rangsang penembakan 1048708 serapan Glu oleh glia 1048708 Na + 1048708 masuknya
ATP dikonsumsi oleh Na-K-ATPase laktat 1048708 1048708 aktivasi glikolisis diangkut ke neuronLokal peningkatan aliran darah meningkat laktat
Excitotoxity = excesive Glu rilisepilepsi cedera otak traumatisNa + dan Ca2 + akumulasi sel intra 1048708 pembengkakan
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Functional imaging PET
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Ammonia handling in the brain NH3 is a waste product of deamination
reactions (GlnGlu Glu 2-oxoglutarate etc) Metabolism
Glutamin synthetase NH3 + Glu Gln Gln is metabolized in the liverkidneys
Ammonia toxicity NH3 + 2OG + NADH Glu + NAD+ Krebs cycle impairment 2-OG depletion Glu excess excitotoxicity
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Ammonia handling Clinical consequences liver disease impairs brain
function principle insufficient urea synthesis NH3
accumulationneurotoxicity Hepatic encephalopathy grI-IV Fulminant liver failure (ie paracetamol poisoning) threatens
live also by ICP Klinis konsekuensi penyakit hati mengganggu fungsi
otakprinsip sintesis urea cukup 1048708 NH3 akumulasi 1048708 neurotoksisitasHepatik ensefalopati grI-IVKegagalan hati fulminan (yaitu parasetamol keracunan) mengancam hidup juga dengan 1048708 ICP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Blood brain barrier selectivity Free permeability (passive diffusion)
small molecules H2O O2 CO2 NH3 ethanol lipid soluble molecules steroid hormones
Carrier mediated transport glucose GLUT-1 (insulin independent) amino acids
Pinocytosis Gratis permeabilitas (difusi pasif)
molekul kecil H2O O2 CO2 NH3 etanollipid larut molekul hormon steroidPembawa dimediasi transportasiglukosa GLUT-1 (insulin independent)asam aminoPinocytosis
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
Areas outside BBB Enables brain to sense and regulate blood
composition
Include Subfornical organ osmoreceptors regulate ADH OVLT dtto thirst Area postrema chemoreceptors vomiting center Mengaktifkan otak untuk merasakan dan mengatur
komposisi darah
termasukOrgan Subfornical osmoreseptor mengatur ADHOVLT dtto hausLuas postrema kemoreseptor muntah pusat
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
BBB ndash clinical significance CNS infection
BBB protects against bacteria entry but also antibodies and antibiotics Kernikterus
hyperbilirubinemia damages the brain in neonates but not in adults Parkinsons disease
=lack of dopamin in basal ganglia cannot be treated with dopamin (does not cross BBB) but its precursor L-
DOPA is usefulSSP infeksi
BBB melindungi terhadap masuknya bakteri tetapi juga antibodi dan antibiotikKernikterushiperbilirubinemia kerusakan otak pada neonatus tetapi tidak pada orang dewasaParkinson penyakit= kurangnya dopamin di ganglia basaltidak dapat diobati dengan dopamin (tidak menyeberangi BBB) tetapi prekursor L-dopa berguna
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
CSF in diagnostics CNS infection
bacterial meningitis viscous and opalescent CSF WBC Glucose Lac viral meningitis few cells protein
Degenerative diseases oligoclonal bands in multiple sclerosis others
Hematologic malignancy leucemic cells infiltrate CNS SSP infeksi
meningitis bakteri CSF kental dan terbuat dr batu baiduri 1048708 1048708 1048708 WBC 1048708 Glukosa 1048708 1048708 Lacvirus meningitis beberapa sel protein 1048708 1048708penyakit degeneratifoligoclonal band pada multiple sclerosisorang lainhematologi keganasansel leucemic menyusup SSP
![Journal 1967 [Owen] Brain Metabolism During Fasting](https://img.pdfslide.us/doc/110x75/577d27911a28ab4e1ea438f3/journal-1967-owen-brain-metabolism-during-fasting.jpg)
