midterm physio deck 4 Flashcards
insulin dependent tissue
muscles and adipose
protein sparing effect of ketones
as ketone production rises, they are used increasingly by the CNS as a fuel –> spares breakdown of muscle in survival situations
glycogen vs fat as storage efficiency
glycogen is inefficient since each gram requires 1-2 g of intracellular watervsfat that is a water free environment
islet cells and their roles
alpha - glucagon secretingbeta - insulin secretingdelta - somatostatin (SRIF) secreting
what cells secrete glucagon?
alpha cells of islet pancreas
SRIF (somatostatin) actions
all actions of somatostatin are INHIBITORYinhibits TSH and GH in pituitaryinhibits insulin and glucagon release in pancreatic islet cells
insulin circulates _____what enzyme breaks it down?
free in plasmaglutathione transhydrogenase (breaks all three disulfide bonds)
does insulin cross placenta?
no
insulin receptor is what type?
tyrosine kinase that autophosphorylates
do insulin receptors use cAMP?
no, it is not a messenger for insulin stimulationtyrosine kinase does notcAMP actually goes down
malonyl coA and insulin
insulin enhances malonyl coa production in hepatocytesmalonyl coa then inhibits the transport of free FA into mitochondria so ketoacids arent made; allows FA biosynthesishigh malonyl coa = low ketogensis
glucagon receptor
Gs protein linked to adenylate cyclase
is there a backup for insulin?
NO
is there a backup for glucagon?
yes4 other catabolic hormones = norepi, epi, cortisol, and GHall correct for hypoglycemiaglucagon and catecholamines are short termcortisol and GH are longer term adaptation
obesity results in what kinds of state?basis for what?
chronic, low grade systemic inflammationbasis for t2 diabetes insulin resistance–elevated levels of pro-inflammatory cytokines act to down regulate insulin receptors
what triggers pro-inflammatory cytokines in obesity?
adipocytes accumulatelipid stores increase in sizeincreased distance oxygen must diffuse cells become hypoxic and upregulate cytokine expressionattracts monocytes and activated into macrophagesleads to systemic proinflammatory state with generalized insulin resistance
type1 vs type 2which is dependent on insulintreatment?
type 1 is insulin dependent - give insulintype 2 is insulin independent - give oral hypoglycemics
2 main mechanisms for Diabetes pathogenesis
1) glycation - exposure of proteins to high glucoseresults in unregulated nonenzymatic glycation –> disrupts structure and function and can cause modified proteins to elicit autoimmune attack on native protein***glycated Hb is a good assessment of glycemic control since Hb has life of 120 days2) accumulation of sorbitol - sorbitol is formed by reduction of glucose by aldose reductase which is activated in diabetics
diabetic microangiopathy
BM thickening in small vesselsmech: hyaline like glycoprotein accumulates in BM resulting in dilation and increased permeabilitycauses retinopathy, neuropathy, and nephropathy w proteinuria and renal failure
diabetic macroangiopathy
progressive occlusion of arteriesleads to angina, MI, claudication, gangrene, ischemic attacks and cerebral infarction
diabetic neuropathy
symmetric sensory loss in distal extremities
less sensation, tingling/burningautonomic = orthostatic hypotensions and GI/urogenital motor distrubances
DKA
diabetic ketoacidosisinsulin deficiency resulting in metabolism disturbances with hyperglycemia and metabolic acidosis due to accumulation of ketoacids, acetoacetic acid, and beta hyroxybutyrateusually glucagon is greatly increased exaccerbating the absence of insulin
DKA mechanism
insulin lack decrease in glucose useliver and muscle glycogenolysis; increased ketogenesishyperglycemialimited ketone body utilization by peripheral tissueglycosuria and osmotic diuresis –> water and electrolyte loss/vomitingdehydration and hemoconcentrationhypotension and decreased renal blood flow; CV depressionanuria/shockcoma/death
DKA effects on lipis
allows unimpeded lipolysis –> elevated plasma free FAs =more ketogenic substratein absence of insulin, hormone sensitive lipase isnt inhibited and continues to break down adipose
DKA and CPT1/maolnyl coa
CPT1 is usually inhibited by malonyl coalow insulin/high glucagon –> decrease in malonyl coa –> CPT1 is no longer inhibited and ketogenesis runs uninhibited!!!
DKA treatment
isotonic saline immediately for fluids!start insulin therapy next slowly and carefully until acidosis is correctedwith electrolytes/ potassium to move potassium back into cellsexogenous glucose/dextrose given to cover the insulin needed to reverse the ketosis
DKA diagnostic criteria
diabetes symptoms and random plasma glucose > 200orfasting plasma glucose > 126or2 hr plasma glucose >200 during glucose tolerance testor Hba1c >6.5DKA = hyperglycemia (>200), Ketonemia/ketonuria, acidosis (ph
clinical features of DKA
polyuria, polydipsia, polyphagia, and nocturiaweightlossketoacidosis: abd pain, N/v, mental changefatigue and weaknessblurry visiongenital yeast infections
why do you need to be careful treating DKA w fluids?
large fluid shifts are a concern for cerebral edema
if serum K is abnormal, do a _____
EKG
cerebral edema
can occur 4-12 hrs after treatment startedcriteria = alterned MS/consiousness, sustained HR deceleration, and age inapropriate incontinence
warning signs of cerebral edema
headache, slowed HR, neuro change (irritable, drowsy), CN palsies, rising BP, decrease O2 stats
diagnostic features of cerebral edema
adnormal motor/verbal response to paindecroticate or decerebrate posturecranial nerve palsy (3,4, 6) abnormal neurogenic respiratory pattern
treatment for cerebral edema
3% saline or mannitolelevate head of bedreduce fluid rate by 1/3intubation and head CT after treatment initiated
do not ____ insulin during DKA/cerebral edema treatment
lowerif glucose falls, just add glucose
pros/cons of NPH and regular insulin
pros: 2-3 shots per day, cheaper; less carb countingcons: strict dietary plan, less flexible or physiologic
pros/cons of basal/ bolus (detemir/glargine and aspart)
pros: more physiologic, flexible, and less hypoglycemiacons: labor intensive, carb counting and atleast 4 injections per day
how basal/bolus works
basal = detemir or glargine at 50% of TDDbolus = aspart(novolog) based on insulin to carb ratioTDD = .5 units/kgratio = 450/TDDcorrection factor = 1800/TDDbolus dose needed= (carbs/carbs ratio) + (BG-target)/CF
how does exercise help diabetic
increases sensitivity to insulin and helps control blood sugarhave snacks available; dont exercise if ketones are present
when diabetic person is ill…
DONT stop insulin - insulin req is often greater with illnesswill need extra insulin to clear ketonesdrink fluids with sugar if hypoglycemic
