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Step I DKA qs
Started by match2011
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In DKA there is a lack of insulin & DKA is precipitated due to some outside cause (viral, infection, etc.) in a Type 1 DM patient.
If you recall the pneumonic from FA for cAMP second messengers:
FLATCHAMP (FSH, LH, etc.) +glucagon, GHRH and calcitonin --->cAMP second messengers
Or if you just know that glucagon is a phosphorylater -->glucagon binds G Protein coupled receptor--> one of its subunits activates Adenylate Cyclase -->cAMP is made-->PKA -->downstream effects of glucagon pathway
Insulin is a de-phosphorylater (protein phosphatase)
If you recall the pneumonic from FA for cAMP second messengers:
FLATCHAMP (FSH, LH, etc.) +glucagon, GHRH and calcitonin --->cAMP second messengers
Or if you just know that glucagon is a phosphorylater -->glucagon binds G Protein coupled receptor--> one of its subunits activates Adenylate Cyclase -->cAMP is made-->PKA -->downstream effects of glucagon pathway
Insulin is a de-phosphorylater (protein phosphatase)
There is an increased glucagon secretion seen in DKA. Glucagon has a Gs coupled receptor, which means that cAMP will increase as a result of the activation of adenyl cyclase. Increased levels of cAMP will activate PKA, which in turn phosphorylates a multitude of different enzymes. As a result of this, some enzymes will be activated whereas some will be inactivated. As a rule of thumb, enzymes that result in increasing blood glucose will be activated and vice versa.
Phosphoprotein phosphatase (PPP) is an enzyme activated by insulin. This enzyme will result in the reversal of the actions of counter insulin hormones such as glucagon. Since DKA results from the lack of insulin, PPP will not be activated.
Phosphoprotein phosphatase (PPP) is an enzyme activated by insulin. This enzyme will result in the reversal of the actions of counter insulin hormones such as glucagon. Since DKA results from the lack of insulin, PPP will not be activated.
Pathogenesis of DKA:
Some initiating insult occurs, causing an acute decrease in insulin and increased counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone, prolactin, etc.). This occurs since throughout millennia of evolution humans have evolved their metabolism to preserve glucose levels at all cost in order to support the brain. Therefore, if there is an acute injurious state the body tends to favor things that increase glucose levels.
Insult-->Acute insulin insufficiency-->decrease glucose use-->increase blood glucose -->glucosuria (once Tm has been exceeded)-->polyphagia due to giving out so many calories in urine-->polydypsia since losing liquids via osmotic action of glucose in urine-->dehydration-->circulatory failure
At the same time since there is a decrease in insulin there is an increase in FFA mobilization -->increase FFA-->increase FFA oxidation-->increase ketone bodies-->increase ketones-->decrease alkali reserve-->acidosis
FFA is the most important culprit as it shuts down glycolysis (PFK, HK, etc. all inhibited)
Protein break down ensues via the same token since there is less insulin-->increase plasma AA-->increased BUN (urea -->increase GNG-->increase glucose-->dehydration and circulatory failure
moral of the story--glucagon is high , insulin is low
Some initiating insult occurs, causing an acute decrease in insulin and increased counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone, prolactin, etc.). This occurs since throughout millennia of evolution humans have evolved their metabolism to preserve glucose levels at all cost in order to support the brain. Therefore, if there is an acute injurious state the body tends to favor things that increase glucose levels.
Insult-->Acute insulin insufficiency-->decrease glucose use-->increase blood glucose -->glucosuria (once Tm has been exceeded)-->polyphagia due to giving out so many calories in urine-->polydypsia since losing liquids via osmotic action of glucose in urine-->dehydration-->circulatory failure
At the same time since there is a decrease in insulin there is an increase in FFA mobilization -->increase FFA-->increase FFA oxidation-->increase ketone bodies-->increase ketones-->decrease alkali reserve-->acidosis
FFA is the most important culprit as it shuts down glycolysis (PFK, HK, etc. all inhibited)
Protein break down ensues via the same token since there is less insulin-->increase plasma AA-->increased BUN (urea -->increase GNG-->increase glucose-->dehydration and circulatory failure
moral of the story--glucagon is high , insulin is low
Insulin has a paracrine effect on alpha-cells in Islets of Langerhans where it inhibits the release of glucagon. So if there is no insulin, no paracrine inhibitory effect, and glucagon can be released from the alpha cells. So really, elevated blood glucose is due to combination of lack of insulin AND increased levels of glucagon.
