diabetic ketoacidosis Flashcards
define diabetes mellitus type 1
- infiltration of white cells & autoimmune destruction of beta cells
what does insulin regulate and what are the counter-regulatory hormones
regulates carbohydrate & lipid metabolism
counter-regulatory hormones = glucagon, catecholamines, cortisol, GH
stimulatory effects of insulin
- glucose uptake in muscle & adipose
- glycolysis
- glycogen synthesis
- protein synthesis
- ion uptake (K)
inhibitory effects of insulin
- gluconeogenesis
- glycogenolysis
- lipolysis
- ketogenesis
- proteolysis
describe glucose uptake
- insulin binds to receptor
- causes translocation of GLUT4 to cell surface -> passive flow of glucose
- also receptor downstream actions = glycogen & FA synthesis, glycolysis
what is required for accelerated ketogenesis
both
- insulin deficiency
- glucagon excess
diagnosis of DKA
- glucose = > 11mmol/L
- venous pH < 7.3
- presence of ketonaemia or ketonuria
potassium feedback mechanism (response to increase K)
aldosterone
- K+ uptake by cells and renal excretion
potassium feedforward mechanism
e.g. what controls K after a meal
insulin
- activates Na/K/ATPase –> K uptake
glucagon & cAMP
- promotes K excretion
how do we make ketones?
- from fat
- liver, increased hepatic fatty acid oxidation
- in mitochondria, FFA -> acetyl CoA
anion gap in DKA
- ketone bodies circulate as anions -> increased AG
what does DKA requires
- lack of insulin
- stress (activate counter-regulatory hormones)
- fat
other controls for K+ gradient
B2 adrenergic stimulation (adrenaline)
= K uptake
acidosis
= K efflux
cell lysis
= releases K (esp muscles, red cells)
exercise
= contraction releases K (repolarisation)
3 key factors that determine K secretion
- activity of Na/K/ATPase on basolateral membrane
- permeability of luminal membrane
- the electrochemical gradient from lumen -> blood
increased distal flow results in what?
decreased K in tubular fluid therefore increased K secretion
(note: diuretics increase flow)
