catecholamines lecture for 2nd year mbbs by dr waseem
DESCRIPTION
2nd year MBBS.lecture by Dr Mohammad WAseem KausarTRANSCRIPT
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catecholamine
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Hormones that regulates fuel metabolism
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Major hormonesAnabolic hormone
insulinCounter regulatory hormone
epinephrinenor epinephrineglucagoncortisolSomatostatinGrowth hormonethyroid hormone
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CATCHOLAMINES
Not necessary for lifeRequired for adaptation to acute & chronic
stressResponse involves integrated adjustmentCatechol can not facilitate stress alone but
aided by others.• are secreted and stored in the adrenal
medulla and released in response to appropriate stimuli
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Responses to Stress
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Synthesis release of Catecholamine
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Ist step = ring hydroxylation
•Tyrosine enter the mitochondria•Rate limiting step and enzyme(TH), cu containing metalloprotein•Function as oxidoreductase•Requires THB as hydrogen donor•Parkinson disease
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Parkinson’s diseaseA chronic progressive disorder
involuntry tremors, dec- motor power and control, muscular regidity,
postural instabilityDeficiency of dopamin in substantia nigraCatcholamine can not cross the B B BDopa is the treatment
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2nd step = decarboxylation
In cytoplasmDopa comes out from mito- to cytoplasmRequires pyridoxal phosphate. α-Methyl dopa resembles L- dopa, a
competitive inhibitor (antihypertensive)
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3rd step = side chain hydroxylation
Dopamine from cytosole enters in to chromaffin- cells
DBH , a mono oxygenaseA cu containing enzyme (cu is oxdized and
reduced back by vit-C)Ascorbic acid as electron donor
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4th step = N- methylation(cytoplasm)
Nor-epi comes out from granules in to cytoplasm
PNMTMethyl group is donated by active
methionineInduced by glucocorticoidThis reaction does not occur in nerves
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Mechanism of Action
• receptor mediated – adrenergic receptors
• peripheral effects are dependent upon the type and ratio of receptors in target tissues
Receptor
Norepinephrine
+++++
++
Epinephrine ++++ ++++Relative effects of epinephrine and norepinephrine on and adrenergic receptors.
Guyton
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Mechanism of Action 1. Catecholamine binds to β1 and β2Activates adenyl cyclaseIncreases cyclic AMPactivates c- AMP dependant protein
kinasePhosphorylates specific proteinsOn binding to α receptors (opposite of
above)2. Binds to α1Formation of IP3 & DAG or increase in ca+
+ as a second messenger.
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Biochemical actionsIncreases blood glucose & lactate1, glycogenolysis in liver & muscles In liver through cyclic AMP dependant protein kinase mediated by
two ways. Through β2 receptors (similar to glucagon). Through α1 receptors In muscles due to absences of g-6-pase does not directly inc-
blood glucose, but inc- blood lactate & pyruvate β effect No Glucagon effect HEART MUSCLE
Increase in cyclic AMP+ve inotropic effect
2, Stimulate ACTH formation glucocor gluconeogenisis
3, Epinephrine onβ cells through α-adrenergic cyclic AMP & insulin release
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Lipolytic actionBoth epi- & nor-epi breakdown of TG in
adipose tissue by increasing c-AMP(β effect), rapid release of FFA and Glycerol
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Gluconeogenic actionEpinephrine(β2effect)
c-AMPSYNTHESIS OF KEY ENZYMES pyruvate- carboxylase PEP carboxykinase fructose 1 6 bi-phos
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Action on glycolysisEpinephrine ----- LA productionNor-epinephrine---- little effect
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Metabolism of the catecholamines by catechol-O-methyltranferase (COMT) and monoamine oxidase (MAO).
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Pheochromocytoma
• a catecholamine-secreting tumor of chromaffin cells of the adrenal medulla
• paraganglioma – a catecholamine secreting tumour of the sympathetic paraganglia
adrenal pheochromocytoma (90%)
extra-adrenal pheochromocytoma
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Signs and Symptoms of Pheochromocytoma
• treatment resistant hypertension (95%)
• headache• sweating• palpitations• chest pain• anxiety• glucose intolerance• increased metabolic rate
classic triad
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Diagnosis and Treatment
• diagnosed by high plasma catecholamines and increased metabolites in urine
• no test for adrenal or extra-adrenal
• treatment is surgical resection