PBL Learning Objectives II Flashcards
What is normal potassium (K+)?
High intracellular Low extracellular (plasma)
What does insulin do to K+?
Insulin drives K+ into cells (activates the Na/K ATPase pump)
What happens to K+ when there is low insulin?
K+ is stuck in the serum
What is the acidosis buffer mechanisms that causes hyperkalemia?
- Blood bicarbonate is depleted (due to ketones)
- Compensation for low blood pH occurs by pushing H+ into cells
- Need to balance incoming + charge by pushing K+ (antiporter) out into the serum
- This results in Hyperkalemia
Why do we need to replace K+ during DKA treatment?
Patient has hyperkalemic serum, but it occurs at the cost of her body cells losing their K+
–> cells are hypokalemic and K+ will need be replaced during treatment
How is K+ lost during diuresis?
Most ketones are secreted as potassium/sodium salts.
–Solutes are bound to ketones and are excreted –> net loss of Na+ (hyponatremia) and K+ is lost in the kidney (contributing to body hypokalemia when treatment restores ability of cells to uptake the K+)
What happens in cases of hyperglycemia?
[Remember intracellular K+ is usually high]
- With hyperglycemia, IC water flows out into the hyperosmotic EC space
- This decreases the IC volume, increasing solute concentrations
- Since H2O left the cell, IC [K+] is even higher
- -> stronger gradient for K+ to leak out of cells into serum (solvent drag) –> K+ can actually flow out thru aquaporins with H2O
What is the mechanism of Tm transport of glucose in the proximal tubule?
Normally = 100% of filtered glucose is reabsorbed in the proximal tubule, from lumen to peritubular capillaries.
-This is done by sodium-glucose transporters, known as SGLTs (sodium-glucose linked transporters)
What sodium glucose transporters absorb the most?
SGLT2s reabsorb 90% of glucose
What is Tm?
Transport maximum - the saturation point of SGLTs
What happens to glucose at the Tm?
Once Tm is reached, you will not be able to reabsorb glucose and it will remain in urine.
At what glucose level does it start to be secreted in urine?
15 mM of glucose = glucosuria
What does glycosuria lead to?
Osmotic diuresis!
In a general sense, what causes orthostatic hypotension in DKA?
Volume depletion –> low blood volume
-Our patient is undergoing osmotic diuresis in response to hyperglycemia
What is the mechanism behind orthostatic hypotension?
- Stand up
- Blood goes to legs, shifts out of central venous compartment to peripheral venous compartment
- Decreased stroke volume
- Decreased BP
- The reflex to decreased BP: decreased baroreceptor firing –> increased sympathetic nervous system –> increased RAAS in kidneys and increased heart rate
When does osmotic diuresis occur?
If the normal tight coupling between sodium and water reabsorption in the proximal tubule is disrupted.
What does diuresis mean?
Increased urine flow
What is osmotic diuresis?
Denotes situation in which increased urine flow is due to an abnormally high amount of any solute that is not reabsorbed at all (ex. mannitol) or is filtered at such a high rate that much is left in the tubule (ex. very high plasma glucose), leaving large amounts of solute in the lumen (INCREASE OSMOLARITY –> More stuff)
How does high serum glucose cause osmotic diuresis?
Normally water is reabsorbed from tubule –> BUT The increased concentration of unabsorbed solutes (glucose) in urine/glucose’s osmotic presence retards the further reabsorption of water (holds water in the lumen).
What happened in our PBL case to case osmotic diuresis?
Filtered load of glucose exceeded the tubular maximum (increased glucose in filtrate) and unreabsorbed glucose acts as an osmotic diuretic.
What is the mechanism of osmotic diuresis?
- Increased blood glucose
- Inc. glomerular filtration of glucose (inc. osmolality of urine)
- Inc. osmotic pressure of renal tubular fluid
- Dec. water reabsorption
- Osmotic diuresis
How much of body fluid is intra and extra cellular??
Intracellular - 2/3
Extracellular - 1/3
Of the extracellular fluid, how much is interstitial and how much is plasma?
3/4 interstitial
1/4 plasma (vasculature - so when you drink something, 3/42 will go into your plasma)
What does osmotic pressure do?
Draws fluid into the capillary
What does hydrostatic pressure do?
Pushes fluid away (out of capillary)
How do osmotic and hydrostatic pressure compare?
Usually they balance each other out throughout the body. The only spot where they don’t balance is in the renal corpuscle –> driving filtration
What drives the osmotic pressure primarily?
Albumin
What drives hydrostatic pressure?
Blood pressure!
What are the two ways to calculate ion gap? What one is more common?
- (Na+ + K+) - (CL- + HCO3-)
2. (Na+) - (Cl- + HCO3-) –> more common
What is the high normal for anion gap calculation (Na+ + K+) - (Cl- + HCO3-)?
16 mEq/L
In our patient = 24.3
What is the normal range for the more common anion gap calculation?
(Na+) - (Cl- + HCO3-)
Normal = 8-12 mEg/L
Our patient = 130 - (98+14) = 18
What does a high anion gap indicate?
Acidosis
What conditions should you think of with a low anion gap?
Multiple Myeloma
What conditions should you think of with a high anion gap?
CAT MUDPILES
What does MUDPILES stand for?
Methanol Uremia (CKF) Diabetic Ketoacidosis Propylene glycol Infection, Iron, Isoniazid, Inborn errors of metabolism Lactic acidosis Ethylene glycol Salicylates
What does CAT MUDPILES stand for?
C - Carbon monoxide, Cyanide, Congenital heart failure
A - Aminoglycosides
T - Teophylline, Toluene (Glue-sniffing)
M - Methanol
U - Uremia
D - Diabetic ketoacidosis, Alcoholic ketoacidosis, Starvation ketoacidosis
P - Paracetamol/Acetominophen, Phenformin, Paraldehyde
I - Iron, Isoniazid, Inborn errors of metabolism
L - Lactic acidosis
E - Ethanol (due to lactic acidosis), ethylene glycol
S - Salicylates/ASA/Aspirin
What does the anion gap represent?
Concentration fo all unmeasured anions in the plasma.
What makes up the majority of unmeasured anion represented by the anion gap?
Negatively charged proteins (aka Albumin) –> accounts for about 10% of plasma anions
What happens to the anion gap in DKA?
When acid anions (lactate, acetobscetate, sulphate) produced during metabolic acidosis the H+ produced reacts with bicarbonate anions (buffering) and the CO2 produced is excreted via the lungs (respiratory compensation).
—> causes net effect of dec. concentration of measured anions (ex. HCO3) & inc. the concentration of unmeasured anions (acid anions) so the anion gap inc!
If a patient is in pure metabolic acidosis, how does pH relate to pCO2?
Last two numbers of the pH = pCO2
ex: 7.32 = 32
How does DKA cause decreased pH?
Ketoacids release H+ producing acidosis
–> Any substance that can dissociate hydrogen ions will produce an acidosis (e.g. Lactate)
What is normal pH range?
7.35-7.45
Why is CO2 blown off after during ketogenesis?
Ketogeneis –> Acetoacetate (weak acid) –> dissociates into (H+) + (RCOO-) –> Increase in (H+) –> Le’Chatlier’s push toward CO2 –> blow
off CO2
How does increased CO2 cause high respiratory rate?
Increased CO2 activates respiration center —> tachypnea
What causes a decrease in pCO2 during metabolic acidosis?
Metabolic acidosis stimulates peripheral chemoreceptors and the respiratory center in the brainstem –> dec. in partial pressure of CO2
How does decreased pCO2 lead to higher ventilation?
Dec. pCO2 drives the bicarbonate reaction away from the acid towards producing more CO2 according to LeChatelier’s Principle
How is bicarbonate effected when ketone bodies are produced?
- Ketone bodies have low pKa –> metabolic acidosis
- Body first buffers change with the bicarbonate buffering system, but this system is quickly overwhelmed
- -> Keto-acids consume serum HCO3- –> low bicarbonate level
Why is bicarbonate depleted in DKA?
- Any acidic substance will produce proteins that will join with bicarbonate to form H2CO3 —> CO2 + H2O.
- The forward reaction of this equation will be driven by Le’Chatlier’s principle away from the high concentration of substrates (large amounts of protons produced by the acid) and toward low concentration of products (CO2 which is being removed via Kussmaul Respirations).
What does pO2 represent? What is normal?
pO2 = pressure of oxygen dissolved in blood and how well oxygen is able to move from eh airspace of the lungs into the blood
Normal > 90 mmHg
What does O2 Sat. not measure?
It does not measure the amount of oxygen in blood –> we would also need to know the hemoglobin level
What DOES O2 Sat measure?
Percent of hemoglobin binding spots that are carrying oxygen
What does O2CT measure?
Amount of oxygen in the blood
