Biochemistry 3: DKA (10 main concepts) Flashcards
What does DKA actually mean? Biochemically, how does this occur?
It happens in (almost exclusively type I) diabetics, and is caused by overproduction of ketone bodies (keto) producing a metabolic acidosis.
Lack of insulin → cells “starve” for glucose → glucagon ↑↑↑ → ketone production ↑↑
DKA – what would the HR, BP, and RR be? Why?
BP ↓, HR ↑, RR ↑ (note: these are generally the vitals you see in all forms of shock/intravascular depletion)
DKA → overproduction of glucose → solvent drag in the kidneys → urinary loss of glucose + H2O → hypovolemia → BP ↓ / RR ↑ → baroreceptor stretch ↓ → HR ↑
(in addition) DKA → ketone body production → metabolic acidosis → respiratory alkalosis → RR ↑
DKA – what is the activity level of pyruvate kinase? Pyruvate dehydrogenase? Hormone-sensitive lipase?
Pyruvate kinase ↓, pyruvate dehydrogenase ↓, hormone sensitive lipase ↑
Recall that MANY questions re: activity levels of enzymes for Step 1 are ACTUALLY asking you about the representative biochemical PROCESS. For example, pyruvate kinase is an important enzyme in glycolysis, so a question asking about pyruvate kinase is actually asking about glycolysis levels, which would be low in this case. Similarly, pyruvate dehydrogenase is also used as the final step in glycolysis, so it would also be low.
Hormone sensitive lipase is used in lipolysis, which would be high, so HSL activity would also be high (note, too, that HSL is directly inhibited by insulin, such that if there was no insulin – like there is in DKA – HSL would be disinhibited).
DKA – what is the activity level of glycogen phosphorylase? Acetyl-CoA carboxylase?Pyruvate carboxylase?
Glycogen phosphorylase ↑, acetyl-CoA carboxylase ↓, pyruvate carboxylase ↑
Recall that MANY questions re: activity levels of enzymes for Step 1 are ACTUALLY asking you about the representative biochemical PROCESS. For example, glycogen phosphorylase is the key-regulated step in glycogenolysis, so its activity would be high in DKA (your body is trying to release glucose because the cells are starved of glucose, because there is no insulin to drive the glucose into cells). Acetyl-CoA carboxylase is the key regulated step in fatty acid synthesis, so its levels would be low (recall that insulin causes an increase in fatty acid synthesis by activating acetyl-CoA carboxylase). Pyruvate carboxylase is an important step in gluconeogenesis, which would also be high.
Is DKA more likely to occur in type I or II diabetes? Both? Why?
It happens in (almost exclusively type I) diabetics
It happens because of a lack of insulin, which fits with type I diabetes, whereas type II diabetes is more because the insulin produced is insufficient, because of insulin resistance.
What is the sodium level of someone in DKA? Why does this make sense, and how do you correct it?
Na levels low (pseudohyponatremia)
Recall that in DKA: insulin ↓↓ → cells “starving” for glucose → glucagon ↑↑ → glucose overproduction → glucose ↑↑ → osmolarity↑↑ → H2O moves from inside to outside of cells → dilutional / pseudohyponatremia
What is the major ion that determines serum tonicity? Why does this make sense?
Sodium is the major ion that determines serum (extracellular) tonicity. This is because of the Na/K ATPase, which pushes Na+ out of cells, and pulls K+ into cells, such that the dominant extracellular ion is Na+.
What is the major ion that determines serum tonicity? Why does this make sense?
Sodium is the major ion that determines serum (extracellular) tonicity. This is because of the Na/K ATPase, which pushes Na+ out of cells, and pulls K+ into cells, such that the dominant extracellular ion is Na+.
In someone in DKA with pseudohyponatremia, would you worry about correcting their low sodium levels too quickly? Why or why not?
Summary:
No–the reason why correcting hyponatremia quickly can be so dangerous is that when you are hyponatremic and HYPOTONIC, you can get rapid shifts in intracelluar/extracellular water when the extracellular osmolarity ↑ quickly. In DKA, there is HYPERTONIC hyponatremia, and thus not a worry for correcting the hyponatremia quickly.
Detailed:
In true hypotonic, hyponatremia, the total osmolarity (the amount of particles dissolved) is LOWER than normal, hence we call this “hypotonic.” Since sodium is the major ion that determines osmolarity/tonicity, when you are truly hyponatremic, this usually will cause hypotonia. When the serum is hypotonic (meaning more water molecules per particle of dissolved stuff than normal), water will shift INTO cells to try to maintain the osmolarity across the cell membrane, causing the inside of cells to ALSO become hypotonic (more water inside cells will dilute out the existing intracellular particles).
The worry with correcting hyponatremia too quickly comes from causing the extracellular OSMOLARITY to increase rapidly, which would cause a rapid shift of water from the inside of cells to the outside to try and balance the osmolarity on either of the cell membrane.
However, in DKA, while you are technically hyponatremic, it is because you are over-producing sugar/ketone bodies, which raises the serum osmolarity. In other words, you are hyponatremic, but normotonic (or even hypertonic). “Correcting” the sodium actually comes because when you give insulin to treat the lack of insulin in DKA, you end up with LESS sugar/ketone bodies in the serum – while the sodium goes up, the glucose/ketone body levels are going down, so the total osmolarity wouldn’t change. As such, there will be no shift of water into/out of cells, since both before and after treating the DKA, the intracellular and extracellular osmolarity is still the same.
What is the total body potassium level of someone in DKA? What happens when you give insulin?
Total body K+ low, because glucose ↑ → osmotic diuresis → K+ loss in urine. Often the serum K+ is normal (or even high), because:
Hyperglycemia → water + K+ efflux from inside to outside of cell (“solvent drag”) → serum [K+] ↑, plus
Intracellular H2O ↓ → intracellular [K+] ↑ → K+ gradient ↑ → K+ efflux ↑
When you give insulin, the serum K+ can drop (often dramatically)
Insulin → Na/K ATPase activity ↑, plus
Hyperglycemia ↓ → K+ shift into cells
