อ.กวีศักดิ์systemic response to injury and sepsis response.pdf · systemic...
TRANSCRIPT
![Page 1: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/1.jpg)
Systemic Response to Injury and Sepsis :Systemic Response to Injury and Sepsis : Metabolic Part
ผศ.นพ.กวีศักดิ์ จิตตวัฒนรัตน
ภาควิชาศัลยศาสตร
คณะแพทยศาสตร มหาวิทยาลัยเชียงใหม
![Page 2: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/2.jpg)
TopicTopic
• Body composition
• Basic applied biochemistryBasic applied biochemistry
• Metabolic change during stress vs starvation
• Hormonal response
![Page 3: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/3.jpg)
Body composition
![Page 4: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/4.jpg)
Body compositionBody composition
Body cell mass = Protein + ICWy
Lean body mass = BCM + ECWLean body mass = BCM + ECW≠Mineral + fat
![Page 5: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/5.jpg)
Body composition changeBody composition change
Catabolic phase↓ Body cell mass & fat↑ ECF
Loss of body mass loss > 25‐30%: Inevitable with life
![Page 6: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/6.jpg)
How can I explain this change?How can I modify this change?
Phase of responseBiochemistry changeBiochemistry changeHormonal changeI l i l hImmunological changeCellular change
![Page 7: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/7.jpg)
Phase of metabolic responsePhase of metabolic response
Cuthbertson .Lancet 1942, 1:433–437
![Page 8: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/8.jpg)
Phase of immunologic responsePhase of immunologic response
Early MOF Late MOFy
SIRS CARS
![Page 9: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/9.jpg)
Attenuate responseAttenuate response
![Page 10: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/10.jpg)
Basic biochemistryBasic biochemistry
• Carbohydrate metabolism
• Protein metabolismProtein metabolism
• Fat metabolism• Metabolic change during starvation VS stress
Ch d i t hChange during stress phase
![Page 11: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/11.jpg)
Why body needs glucose?Why body needs glucose?
• Obligate glycolytic cell – Brain and neurons
– Immune cell
Red blood cell– Red blood cell
– Renal parenchymal cell
• Regulate TCA cycle or Kreb’s cycle – NADPH+H + NADPH+H
– Energy
![Page 12: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/12.jpg)
Glycolysis and KetogenesisGlycolysis and KetogenesisGlucose
GlycolysisGlycolysis pathwaypathway
Pyruvate
Pyruvate Dehydrogenase complexPyruvate Dehydrogenase complex Fatty acidPyruvate Dehydrogenase complex(PDHC)
Pyruvate Dehydrogenase complex(PDHC)
Acetyl CoA
y
Acetyl‐CoA
Tricarboxylic acid cycley yKetone production
![Page 13: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/13.jpg)
Cytosol
Mit h d iMitochrondria
![Page 14: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/14.jpg)
Fasting ketogenesis pathwayFasting ketogenesis pathwayGlucose
GlycolysisGlycolysis pathwaypathway
Pyruvate
Pyruvate Dehydrogenase complexPyruvate Dehydrogenase complex Fatty acidPyruvate Dehydrogenase complex(PDHC)
Pyruvate Dehydrogenase complex(PDHC)
Acetyl CoA
y
Acetyl‐CoA
Tricarboxylic acid cycley yKetone production
![Page 15: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/15.jpg)
Stress ketogenesis pathwayStress ketogenesis pathwayGlucose
GlycolysisGlycolysis pathwaypathway
Pyruvate
Pyruvate Dehydrogenase complexPyruvate Dehydrogenase complex Fatty acidPyruvate Dehydrogenase complex(PDHC)
Pyruvate Dehydrogenase complex(PDHC)
Acetyl CoA
y
Acetyl‐CoA
Tricarboxylic acid cycley yKetone production
![Page 16: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/16.jpg)
Glycolysis pathwayy y p y
Glucose Glucose 6 P
GK
Glucose Glucose‐6‐PG6Pase
Glyceral dehyde ‐3‐P
PyruvatePyruvateIrreversible in mammal
Acetyl CoA (TCA)
![Page 17: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/17.jpg)
Glycogenolysis pathwayGlycogen
Glucose Glucose 6 PGlucose Glucose‐6‐P
Glyceral dehyde ‐3‐P
PyruvatePyruvate
Acetyl CoA
![Page 18: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/18.jpg)
Glycogenolysis pathway in liverGlycogen
Glucose Glucose 6 P
GK GlycogenTotal : 300‐400g
Glucose Glucose‐6‐PG6Pase
Liver : 75‐100gMuscle: 200‐250g
Glyceral dehyde ‐3‐P
PyruvatePyruvate
Acetyl CoA
![Page 19: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/19.jpg)
Glycogenolysis pathway in muscleGlycogen
Glucose Glucose 6 P
GK GlycogenTotal : 300‐400g
Glucose Glucose‐6‐PG6Pase
Liver : 75‐100gMuscle: 200‐250g
Glyceral dehyde ‐3‐P
PyruvatePyruvate
Acetyl CoA
![Page 20: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/20.jpg)
Pentose monophosphate shuntGlycogen
Glucose Glucose 6 P
6‐P‐Gluconate
Glucose Glucose‐6‐P NADP
Glyceral dehyde ‐3‐PNADPH+H+
PyruvatePyruvate
Acetyl CoA
![Page 21: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/21.jpg)
Gluconeogenesis – Cori cycleGlycogen
Cori cycle
Glucose Glucose 6 P
6‐P‐GluconateGK
y
Glucose Glucose‐6‐PG6Pase
Glyceral dehyde ‐3‐P
Pyruvate LactatePyruvate Lactate
Acetyl CoA
![Page 22: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/22.jpg)
Gluconeogenesis – Alanine‐Glucose cycle
GlycogenAlanine ‐Glucose cycle
Glucose Glucose 6 P
6‐P‐GluconateGK
y
Glucose Glucose‐6‐PG6Pase
Glyceral dehyde ‐3‐P
Pyruvate AlaninePyruvate Alanine
Acetyl CoAGlutamine
![Page 23: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/23.jpg)
GlutamineGlutamine
BCAA
Alanine
![Page 24: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/24.jpg)
TriglycerideTriglyceride
Glycerol Fatty acidsy y
![Page 25: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/25.jpg)
Gluconeogenesis – Triglyceride
GlycogenFatty acid and Ketone could not produce new glucose
Glucose Glucose 6 P
6‐P‐GluconateGK
y p g
Glucose Glucose‐6‐PG6Pase
Glycerokinase (Liver/kidney)
Glyceraldehyde ‐3‐P Glycerol
PyruvatePyruvate
Acetyl CoA Fatty acid, Ketone
![Page 26: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/26.jpg)
Triglyceride metabolism – Normal
Lipoprotein lipaseBlood vessel
Triglyceride (VLDL chylomicron) Glycerol + Fatty acid(VLDL, chylomicron)
Triglyceride lipaseAdipose tissue
Triglyceride Glycerol + Fatty acidTriglyceride y y
![Page 27: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/27.jpg)
Triglyceride metabolism ‐ Fasting
Lipoprotein lipaseBlood vessel LiverKid
Albumin
Triglyceride (VLDL chylomicron) Glycerol + Fatty acid
Kidney
(VLDL, chylomicron)
Triglyceride lipaseAdipose tissue
ANS etc+ve
Triglyceride Glycerol + Fatty acid
ANS etc
Triglyceride y y
Lipolysis
![Page 28: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/28.jpg)
Triglyceride metabolism ‐ Stress
Lipoprotein lipaseBlood vessel TNF‐α‐ ve
Triglyceride (VLDL chylomicron) Glycerol + Fatty acid
TNF α
(VLDL, chylomicron)
Triglyceride lipaseAdipose tissue
Cathecholamine +ve
Triglyceride Glycerol + Fatty acid
CortisolGlucagon etc
Triglyceride y y
Lipolysis
![Page 29: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/29.jpg)
Triglyceride metabolism – insulin
Lipoprotein lipaseBlood vesselI li
+ve
Triglyceride (VLDL chylomicron) Glycerol + Fatty acid
Insulin
(VLDL, chylomicron)
Triglyceride lipaseAdipose tissue
Insulin‐ve
Triglyceride Glycerol + Fatty acidTriglyceride y y
TGDHTGDHLipogenesis
![Page 30: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/30.jpg)
Fat transporter systemFat transporter system
Stress condition
Impair long chain fatty acid metabolism in stress
CPT I, CPT II = Carnitine palmitoyl transferases I and II
![Page 31: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/31.jpg)
Starvation VS Stress
![Page 32: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/32.jpg)
Early Fasting Man (70kg)
Muscle LiverBrain
Glycogen 75g RBCProtien75g
Gluconeogenesis
WBCKidney
G180g
20%Fat stores GluconeogenesisMuscle
Triglyceride160 L&P 36g
20%
Oxidation160 g
‐ G 16g
L&P 36g
HeartKidneyM l
‐ FA 160g120g
Muscle
![Page 33: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/33.jpg)
Late Fasting Man (70kg) KidneyGluconeogenesis
L&P 44g (55%)
Muscle LiverBrain
Gluconeogenesis
50%
Glycogen 75g RBCProtien20g
Gluconeogenesis
WBCKidney
G80g
45%Fat stores GluconeogenesisMuscle
Triglyceride180 L&P 36g (45%)
45%50%
Oxidation180 g
‐ G 18g
L&P 36g (45%)
Brain58gUrine10g
HeartKidney
‐ FA 180g135g
KidneyMuscle
![Page 34: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/34.jpg)
Stress and trauma (70kg) KidneyGluconeogenesis
L&P 180g (50%)
Muscle LiverWound
Gluconeogenesis
Glycogen 75g RBCProtien250g
Gluconeogenesis
WBCKidney
G360g
Fat stores GluconeogenesisMuscle
Triglyceride170
50%
L&P 180g (50%)Oxidation170 g
‐ G 17g
L&P 180g (50%)
HeartKidneyM l
‐ FA 170g130g
Muscle
![Page 35: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/35.jpg)
Cause of injury Accumulate 10 days N loss (g)Cause of injury Accumulate 10 days N loss (g)
Major burnM lti l i j
170150Multiple injury
PeritonitisB f t
150136115Bone fracture
Major surgeryMi
1155024Minor surgery 24
Ad lt 1 it l L b d 0 04 0 05%Adult : 1 g nitrogen loss = Lean body mass 0.04‐0.05%
25‐30% LBM loss Dead25 30% LBM loss Dead
Mortality N loss threshold =500‐750 gy g
![Page 36: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/36.jpg)
Hormonal response
![Page 37: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/37.jpg)
Membrane receptorsMembrane receptors
![Page 38: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/38.jpg)
Cytosol receptorCytosol receptor
Need time to action
![Page 39: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/39.jpg)
Axis ClassificationAxis Classification
HPT
Pituitary
Effector
![Page 40: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/40.jpg)
CRH – ACTH – Adrenal axisCRH – ACTH – Adrenal axis
![Page 41: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/41.jpg)
Cortisol /GlucocorticoidCortisol /Glucocorticoid
• Effect of cortisol– Increase blood sugar due to synergistic to glucagon g y g g gand catecholamine
– Amino acids release from skeletal muscleAmino acids release from skeletal muscle
– Fat mobilization from adipose tissue
i l i– Hepatic gluconeogenesis
– Insulin resistance
– Decrease inflammatory response (↓TNF‐α, IL‐1, IL‐6 and ↑IL‐10 )
![Page 42: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/42.jpg)
TRH – TSH –thyroid axisthyroid axis
↑ glucose uptake↑glucose oxidation
↑cellular metabolism ↑oxygen consumption
![Page 43: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/43.jpg)
Thyroid metabolism in acute and chronic patients
Euthyroid sick syndrome
Cortisol,Dopamine‐ve
, p
‐ve
ProinflammationProinflammation
![Page 44: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/44.jpg)
GHRH – GH – IGF 1GHRH – GH – IGF‐1
• GHRH Hyperglycemia• GHRH • Autonomic stimulation • thyroxine
• Hyperglycemia• Hyperlipidemia• Somatostatin
• AVP • ACTH• Glucagons
• Beta adrenergic stimulation
• Sex hormone
GHGH+
IGF 1
+
IGF‐1
![Page 45: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/45.jpg)
Effect of GHEffect of GH
i ff• Direct effect– ↑ lipolysis– ↑ protein synthesis– Water and sodium retention Positive
Nit• Indirect effect via IGF‐1
↑ glycogenesis
NitrogenBalance
– ↑ glycogenesis– ↑ lipolysis↑ t i th i– ↑ protein synthesis
• GH and IGF‐1 decrease in injured pts
![Page 46: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/46.jpg)
ProlactinProlactin
• CRH
• TRH
• LHRH
• GnRH Prolactin+• GHRH
• Serotonin
• Dopamine Prolactin+ ‐
• VIP
Immunostimulation :lymphocyte proliferation , IL‐2 , IFN‐γImmunostimulation :lymphocyte proliferation , IL 2 , IFN γSuppress sex hormone : amenorhea
Increase in injured patients
![Page 47: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/47.jpg)
VasopressinVasopressin
(ADH)
![Page 48: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/48.jpg)
CatecholaminesCatecholamines
• epinephrine(Epi) norepinephrine(NE)– Glycogenolysis – T3,T4 – Gluconeogenesis
– Lipolysis– parathyroid hormone
– renin– Ketogenesis– ↓ insulin
– Neutrophilia& lymphocytosis
– ↑ glucagon
![Page 49: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/49.jpg)
Renin – Angiotensin – AldosteroneRenin Angiotensin Aldosterone
ACTH
Refill phenomenon
![Page 50: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/50.jpg)
InsulinInsulin• Effect
– Glycogenesis
• Two phase after injury– Phase I : Insulin deficiency
– Lipogenesis
– Proteogenesis
– Phase II : Insulin resistance
• Improve immune function p
Ti ht t lAnabolic hormone Tight control blood sugar
![Page 51: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/51.jpg)
GlucagonGlucagon
• Action– Glycolysis
– Gluconeogenesis
– Lipolysis & ketogenesis75% of blood sugar
↑ blood sugar
Catabolic hormoneCatabolic hormone
![Page 52: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/52.jpg)
Hyperosmolarity Glycosuria osmotic diuresis dehydration
Insulin resistance ( l i i )
HYPERGLYCEMIA
(glucose toxicity)
HYPERGLYCEMIA(acute severe in hospitalized patient)
Impaired wound healing (collagenSk l t l l healing (collagen glycosylation)
Immune
Skeletal muscle proteolysis
dysregulation
MacrophagesOxidative stress
(proinflammatory)
p g
Neutrophils
I l b li(p y)
Immunoglobulins
Complement
![Page 53: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/53.jpg)
Glycemic Control in SepsisGlycemic Control in Sepsis
• Hyperglycemia alters macrophage function
• Hyperglycemia is proinflammatoryHyperglycemia is proinflammatory• NF kappa B activated with modest hyperglycemia
(Diabetes 1999)(Diabetes 1999)
• Hyperglycemia activates TNF through oxidant stress (inhibited via antioxidants) (JBC 2000)( ) ( )
• Hyperglycemia induces oxidative stress via PKC (Diabetes 2003)
![Page 54: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/54.jpg)
Tight control of blood sugarTight control of blood sugar
![Page 55: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/55.jpg)
Glucose and Insulin after Preop. and Postop. Gl I f i T tGlucose Infusion Tests
25
200
240
20
25GlucoseIRI
160
00
15GLUCOSE p
80
12010
(mmol/L) IRI
mU/L
405
005 30 60 90 5 30 60 90
PREOPERATIVE POSTOPERATIVE
MINUTES GITest
PREOPERATIVE POSTOPERATIVE
Giddings et al. Ann Surg 1977;186:681‐686
![Page 56: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/56.jpg)
Reduction in Insulin Sensitivity afterDifferent Surgical Procedures
100
80
100 % reduction
60
40
0
20
0Lap Chol Hernia Op Chol Colorectal
A. Thorell, J. Nygren, O. Ljungqvist. Curr Op Clin Nutr Met Care 1999
![Page 57: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/57.jpg)
Intensive Insulin Therapy in Critically Ill P ti tPatients
1548 patients with critical illness
783Control
(BS=180 200 mg%)
765Intensive Rx
(BS 80 110 mg%)(BS=180‐200 mg%) (BS=80‐110 mg%)
MR =20.2% MR =10.6%
Greet Van den Berghe, et al. NEJM 2001; 345:1359‐67
![Page 58: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/58.jpg)
Intensive insulin therapy in critically ill patients
Van den Berghe G et al, NEJM 2001
![Page 59: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/59.jpg)
Possible mechanismPossible mechanism
• Hyperglycemic effects– Glucose transporterp
• Insulin effect
GLUT 1 – BBB, GI, Kidney except Liver muscleGLUT 2 Beta cell of pancreasGLUT 2 – Beta cell of pancreasGLUT 3 – Most tissueGLUT 4 Muscle (Correlate to insulin resistance)GLUT 4 – Muscle (Correlate to insulin resistance)GLUT 5 – Fructose transporter
![Page 60: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/60.jpg)
Possible mechanismPossible mechanism
• Hyperglycemic effects– ↑ GLUT 1,3 Transporter in critically ill pts↑ , p y p
– ↓ GLUT 4 Transporter ↑ insulin resistance
↑ Glucose ↑Glucose flux via GLUT 1 3– ↑ Glucose ↑Glucose flux via GLUT 1,3 receptors
• Insulin effect
↑ expression of GLUT 4 ↓ insulin resistance↑ expression of GLUT 4 ↓ insulin resistance
Anabolic effect of insulin
![Page 61: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/61.jpg)
SummarySummary
• Body composition : Changing of body compositionp
• Basic applied biochemistry : CHO, Protein, Fat
M b li h d i i• Metabolic change during stress vs starvation
• Hormonal response and modulate of response p pcould be improve outcome of treatment.
![Page 62: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/62.jpg)
Bundle of treatments are important to flight the injured or septic patientsthe injured or septic patients
![Page 63: อ.กวีศักดิ์Systemic Response to Injury and Sepsis Response.pdf · Systemic Response to Injury and Sepsis : ... Major burn Mltilij 170 Multiple injury 150 Peritonitis](https://reader034.vdocuments.site/reader034/viewer/2022042210/5eae6749c280ad774855699e/html5/thumbnails/63.jpg)
คณะแพทยศาสตร เชยีงใหมคณะแพทยศาสตร เชยีงใหม
ขอบคณครับขอบคณครับขอบคุณครบขอบคุณครบ