Diabetic Ketoacidosis - Gunn Flashcards
Carbohydrate metabolism
glucose and lipid metabolism regulated by the pancreatic horn insulin, and its counter regulatory hormones
- glucagon
- catecholamines
- Cortisol
- Growth hormone
translocation of GLUT 4 glycogen synthesis and fatty acid synthesis
How do we makes ketones?
by metabolising fat, vis beta oxidation by glycogen
in liver by increasing hepatic fatty acid oxidation
ketones require lack of insulin and excess glucagon
= Insulin deficiency +accelerated ketogenesis + glucagon excess.
Intracellular production ketones
in mitochondria
FFA –> acetyl CoA
Increased anion gap, because ketones circulate as anions
Urine ketones, detection and significance
ketone strips use nitroprusside reaction to produce a purple colour in the presence of acetoacetate (AcAc)
Acetone is detected only if the reagent contains glycine in addition to sodium nitroprusside, doesnt detect beta hysdroxybutyrate (BOHB)
Normally serum BOHB :AcAc ~ 1:1 but in acidosis 1.3:1 to 1.5.:1
Plasma or urine AcAc concentration alone underestimate the severity of ketonemia
Criteria to diagnose DKA
Current: hyperglycaemia (blood glucose >11mmol/L), venous pH <7.3 or bicarbonate <15mmol/L, and the presence of ketonemia or ketonuria
Suggested hyperglycaemia: blood glucose > 11mmol/L + venous pH <7.3 + serum BOHB > 3mmol/L
DKA = relative lack of insulin and stress
Insulin (anabolic)
- glucose used for energy substrate or stored as glycogen
- protein formation
- fats stored as triglycerides
Counter regulatory hormones (catabolic)
- GLyconeolysis
- Proteolysis - gluconeogenesis
- Lipolysis - FFA and ketone bodies
popular method of keeping diabetics alive before the insulin era
DKA requires
- lack of insulin
- stress (to activate counter regulatory system)
- Fat (if no TG’s, no NEFA, no ketone bodies can be made)
So patients have lack of insulin but no fat and no stress so therefore no ketones. She is slowly starving to death.
Where in the body is all the K+
In the cells - Only 2% of the K+ is in the ECF ~= intake - Immediate (shift) Late: excrete mean ECF K+ is highly regulated
What controls K after a meal
Insulin –> Na/K ATPase –> K uptake
- not linked to glucose uptake (GLUT4)
- consumption of a meal containing glucose or amino acid stimulates K shift, independent of [K]
Some evidence for glucagon and cAMP
- Protein rich meal –> inc [glucagon] + cAMP
Glucagon portal vein infusion –> inc transtubular K+ gradient + GFR –> 2 x K excretion
Gut factor
Feedback response to increased [K]
backup to prevent major changes
aldoserine –> K uptake by cells (as well as excretion)
Renal excretion
other controls for K gradient
Beta 2 adrenergic stimulation (NA/A) Shift K from ECF --> ICF Beta blockers tend to increase s[K] Acidosis increases K loses from cells - by inhibiting Na/K ATPase Cell lysis e.g. muscle, re cells
Other shifts increasing serum [K]
Exercise
physiological: contraction release of K
Combined with beta blocker or low insulin
Inc ECF osmolarity e.g. diabetes mellitus
- inc ECF osmolarity –> water out of cells –>
- Inc ICF [K] –> inc ECF [K]
The reverse is also correct
Renal excretion is faster and greater than retention
the kidney is able to excrete very large amounts of k+
- Max secretion can be > GFR filtration
The kidney is slow to conserve K
- fractional K excretion can be reduced to ~2% of the filtered load
Thus K depletion with hypokalemia can result is K intake is restricted
Most variation in K secretion happens?
In the DCT and CD
What are the 3 key factors determining K secretion
Activity of Na/K ATPase on basolateral membrane
Permeability of luminal membrane
The electrochemical gradient from the lumen –> blood
