PBL Learning Objectives II

Question 1

What is normal potassium (K+)?

Answer 1

High intracellular
Low extracellular (plasma)

Question 2

What does insulin do to K+?

Answer 2

Insulin drives K+ into cells (activates the Na/K ATPase pump)

Question 3

What happens to K+ when there is low insulin?

Answer 3

K+ is stuck in the serum

Question 4

What is the acidosis buffer mechanisms that causes hyperkalemia?

Answer 4

1. Blood bicarbonate is depleted (due to ketones)
2. Compensation for low blood pH occurs by pushing H+ into cells
3. Need to balance incoming + charge by pushing K+ (antiporter) out into the serum
4. This results in Hyperkalemia

Question 5

Why do we need to replace K+ during DKA treatment?

Answer 5

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

Question 6

How is K+ lost during diuresis?

Answer 6

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+)

Question 7

What happens in cases of hyperglycemia?

Answer 7

[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

Question 8

What is the mechanism of Tm transport of glucose in the proximal tubule?

Answer 8

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)

Question 9

What sodium glucose transporters absorb the most?

Answer 9

SGLT2s reabsorb 90% of glucose

Question 10

What is Tm?

Answer 10

Transport maximum - the saturation point of SGLTs

Question 11

What happens to glucose at the Tm?

Answer 11

Once Tm is reached, you will not be able to reabsorb glucose and it will remain in urine.

Question 12

At what glucose level does it start to be secreted in urine?

Answer 12

15 mM of glucose = glucosuria

Question 13

What does glycosuria lead to?

Answer 13

Osmotic diuresis!

Question 14

In a general sense, what causes orthostatic hypotension in DKA?

Answer 14

Volume depletion –> low blood volume

-Our patient is undergoing osmotic diuresis in response to hyperglycemia

Question 15

What is the mechanism behind orthostatic hypotension?

Answer 15

1. Stand up
2. Blood goes to legs, shifts out of central venous compartment to peripheral venous compartment
3. Decreased stroke volume
4. Decreased BP
5. The reflex to decreased BP: decreased baroreceptor firing –> increased sympathetic nervous system –> increased RAAS in kidneys and increased heart rate

Question 16

When does osmotic diuresis occur?

Answer 16

If the normal tight coupling between sodium and water reabsorption in the proximal tubule is disrupted.

Question 17

What does diuresis mean?

Answer 17

Increased urine flow

Question 18

What is osmotic diuresis?

Answer 18

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)

Question 19

How does high serum glucose cause osmotic diuresis?

Answer 19

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).

Question 20

What happened in our PBL case to case osmotic diuresis?

Answer 20

Filtered load of glucose exceeded the tubular maximum (increased glucose in filtrate) and unreabsorbed glucose acts as an osmotic diuretic.

Question 21

What is the mechanism of osmotic diuresis?

Answer 21

1. Increased blood glucose
2. Inc. glomerular filtration of glucose (inc. osmolality of urine)
3. Inc. osmotic pressure of renal tubular fluid
4. Dec. water reabsorption
5. Osmotic diuresis

Question 22

How much of body fluid is intra and extra cellular??

Answer 22

Intracellular - 2/3

Extracellular - 1/3

Question 23

Of the extracellular fluid, how much is interstitial and how much is plasma?

Answer 23

3/4 interstitial

1/4 plasma (vasculature - so when you drink something, 3/42 will go into your plasma)

Question 24

What does osmotic pressure do?

Answer 24

Draws fluid into the capillary

Question 25

What does hydrostatic pressure do?

Answer 25

Pushes fluid away (out of capillary)

Question 26

How do osmotic and hydrostatic pressure compare?

Answer 26

Usually they balance each other out throughout the body. The only spot where they don't balance is in the renal corpuscle --> driving filtration

Question 27

What drives the osmotic pressure primarily?

Answer 27

Albumin

Question 28

What drives hydrostatic pressure?

Answer 28

Blood pressure!

Question 29

What are the two ways to calculate ion gap? What one is more common?

Answer 29

1. (Na+ + K+) - (CL- + HCO3-) | 2. (Na+) - (Cl- + HCO3-) --> more common

Question 30

What is the high normal for anion gap calculation (Na+ + K+) - (Cl- + HCO3-)?

Answer 30

16 mEq/L | In our patient = 24.3

Question 31

What is the normal range for the more common anion gap calculation?

Answer 31

(Na+) - (Cl- + HCO3-) Normal = 8-12 mEg/L Our patient = 130 - (98+14) = 18

Question 32

What does a high anion gap indicate?

Answer 32

Acidosis

Question 33

What conditions should you think of with a low anion gap?

Answer 33

Multiple Myeloma

Question 34

What conditions should you think of with a high anion gap?

Answer 34

CAT MUDPILES

Question 35

What does MUDPILES stand for?

Answer 35

``` Methanol Uremia (CKF) Diabetic Ketoacidosis Propylene glycol Infection, Iron, Isoniazid, Inborn errors of metabolism Lactic acidosis Ethylene glycol Salicylates ```

Question 36

What does CAT MUDPILES stand for?

Answer 36

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

Question 37

What does the anion gap represent?

Answer 37

Concentration fo all unmeasured anions in the plasma.

Question 38

What makes up the majority of unmeasured anion represented by the anion gap?

Answer 38

Negatively charged proteins (aka Albumin) --> accounts for about 10% of plasma anions

Question 39

What happens to the anion gap in DKA?

Answer 39

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!

Question 40

If a patient is in pure metabolic acidosis, how does pH relate to pCO2?

Answer 40

Last two numbers of the pH = pCO2 | ex: 7.32 = 32

Question 41

How does DKA cause decreased pH?

Answer 41

Ketoacids release H+ producing acidosis | --> Any substance that can dissociate hydrogen ions will produce an acidosis (e.g. Lactate)

Question 42

What is normal pH range?

Answer 42

7.35-7.45

Question 43

Why is CO2 blown off after during ketogenesis?

Answer 43

Ketogeneis --> Acetoacetate (weak acid) --> dissociates into (H+) + (RCOO-) --> Increase in (H+) --> Le'Chatlier's push toward CO2 --> blow off CO2

Question 44

How does increased CO2 cause high respiratory rate?

Answer 44

Increased CO2 activates respiration center ---> tachypnea

Question 45

What causes a decrease in pCO2 during metabolic acidosis?

Answer 45

Metabolic acidosis stimulates peripheral chemoreceptors and the respiratory center in the brainstem --> dec. in partial pressure of CO2

Question 46

How does decreased pCO2 lead to higher ventilation?

Answer 46

Dec. pCO2 drives the bicarbonate reaction away from the acid towards producing more CO2 according to LeChatelier's Principle

Question 47

How is bicarbonate effected when ketone bodies are produced?

Answer 47

1. Ketone bodies have low pKa --> metabolic acidosis 2. Body first buffers change with the bicarbonate buffering system, but this system is quickly overwhelmed - -> Keto-acids consume serum HCO3- --> low bicarbonate level

Question 48

Why is bicarbonate depleted in DKA?

Answer 48

1. Any acidic substance will produce proteins that will join with bicarbonate to form H2CO3 ---> CO2 + H2O. 2. 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).

Question 49

What does pO2 represent? What is normal?

Answer 49

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

Question 50

What does O2 Sat. not measure?

Answer 50

It does not measure the amount of oxygen in blood --> we would also need to know the hemoglobin level

Question 51

What DOES O2 Sat measure?

Answer 51

Percent of hemoglobin binding spots that are carrying oxygen

Question 52

What does O2CT measure?

Answer 52

Amount of oxygen in the blood