Renal Handling Of H+/HCO3- Flashcards Preview

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1

What is normal physiological pH?

7.35-7.45

Acidemia = < 7.35

Alkalosis = > 7.45

PH range that is comparable with life = 6.8-8.0
- anything outside of this range for an extended period of time = death

2

How does the concentration of protons change with respect to shortcut pH values?

Changes in 1.0 pH = 10x fold
- i.e: 7.0 ->6.0 pH =
1 x10^-7 -> 1 x 10^-6 H+ concentrations

Changes in 0.3 pH = 2x fold
- i.e 7.4 -> 7.1 pH = 4 x 10^-8 -> 8 x 10^-6

Changes in concentration fo H+ ions and pH exists on a logarithmic relationship, not linear

3

The three main mechanisms that contribute to maintaining pH in the normal range

1) buffering of H+ in both ECF/ICF

2) Respiratory compensation

3) Renal compensation

4

What are the most important extracellular buffers?

Bicarbonate: most important ECF buffer
HA form = CO2
A- form = HCO3-
- is the first line of defense when H+ is added or lost from the body
- normal HC03- concentration = 24 mEq/L
- CO2 form of bicarbonate is volatile and easily expired
- **when a strong acid is added to bicarbonate solutions = becomes carbonic acid and then dissociates into CO2/H20 and excreted via lungs

Phosphate
HA form = H2PO4(-)
A- form = HPO4(2-)
**when a strong acid is added to HPO4(2-) it becomes H2PO4(-) which is excreted by the kidneys**

5

Henderson-hasselbach equation purpose

CO2 from atmosphere combines with water to form carbonic acid spontaneously

Carbonic acid will break down into protons and bicarbonate via carbonic anhydrase into H+ and HCO3-

Net reaction: CO2 + H20 -> H+ + HCO3-

6

Henrys law

A concentration of a dissolved gas is directly related to its partial pressure

7

Why is bicarbonate buffer system more effective than phosphate buffer?

Bicarbonate (24 mmol/L) is much higher concentration that phosphate (1-2 mmol/L)

The acid form of bicarbonate is CO2 which is volatile and can be excreted via lungs

The base form of bicarbonate is HC03- which can be excreted via kidneys

8

How does calcium change in acidemia vs alkalemia?

Acidemia = ionized calcium (free)
- albumin proteins release non ionized calcium to bind excess H+ ions
- produces hypercalcemia

Alkalemia = non-ionized calcium (bound)
- albumin proteins bind more calcium due to deficiency of H+ ions in blood
- produces hypocalcemia

9

Most important intracellular buffers

Includes organic phosphates (ADP/ATP), DPG and proteins (especially hemoglobin which is most significant)

In order to be used, H+ has to get into cells via 1 of 3 ways:
-1) conditions where there is an excess or deficit of CO2 (respiratory acidosis)
-2) conditions where there is excess fixed acids in the blood (H+ can attach to lactate for example)
-3) conditions where there is excess H+ with no organic anion (switch’s with K+ to get into cell)

10

Reabsorption of filtered bicarbonate

1) bicarbonate binds to H+ ions that are secreted via sodium/H+ exchanger channels on the lumen surface of primarily the PCT (but also DCT and CD).
- forms carbonic acid via carbonic anhydrase

2) carbonic anhydrase cleaves carbonic acid into CO2/H20 which easily diffuse into the PCT cells

3) CO2/H20 then recombine into carbonic acid via carbonic anhydrase and then also break down into H+/HCO3- ions
- essentially step 1 in reverse

4) bicarbonate is then reabsorbed via Na+/bicarbonate cotransporter channels and Cl-/HCO3- exchangers on the basolateral surface

11

Where does excretion of titratable acid occur?

*also one way to create new bicarbonate*

In the a-intercalated cells of the collecting duct and very late DCT

1) secretes H+ ions into the lumen and bind to phosphate ions and generate H2PO4- which is excreted

2) a-intercalated cells use carbonic anhydrase to form and break apart carbonic acid into H+/HCO3- ions
- this bicarbonate is reabsorbed via bicarbonate/Cl- exchanges on the basolateral surface
- ***this is termed “new” bicarbonate***

12

Excretion of NH4+ occurs where?

*also the 2nd area to reabsorb new HCO3-*

In PCT/TAL/(a)-intercalated cells
- (primarily PCT though)

1) ammonium ions (NH4+) are generated inside PCT cells via break down of glutamine -> glutamate +(NH4+)-> a-ketoglutarate -> HCO3-
- **this generates new HCO3- which is reabsorbed while also generating NH4+

2) these ammonium ions (NH4+) spontaneously break apart into NH3 + H+ so NH3 can leave the cell and go into the lumen

3) ammonia (NH3+) ions that are found in the lumen uptake H+ ions that get into the lumen via Na+/H+ exchanger channels found on lumen and form NH4+

4) NH4+ is readily excretable since it cant be reuptaken unless pathology is present

**HCO3- made in step 1 is reabsorbed via Na+/HCO3- cotransporter on basolateral side**

13

Winters formula

Gives the expected PCO2 based on a measured HCO3- concentration

Used to determine respiratory compensation for a metabolic acidosis

**PCO2 = [(1.5 x HCO3-) + 8] +/-2**

14

Anion gap

Anion gap = (Na+)-(Cl- + HCO3-)
- normal = 8-12 mEq/L
- high = > 12 mEq/L


Must check this if metabolic acidosis is present in a patient since this tells you possible underlying pathologies

15

How does intracellular and extracellular pH differ?

Intracellular =7.2

Extracellular = 7.4

Na+/H+ channels = move H+ out of ICF = more alkaline intracellular

Cl-/HCO3- channels = moves HCO3- out of cells = more acidic intracellular

16

Difference between Volatile and nonvolatile/fixed acids

Volatile acid = CO2
- becomes carbonic acid (weaker acid) when combined with H20
- dissociates into H+/HCO3- and travels through the blood to lungs. Here the reaction reverses and CO2 is expelled (or vise versa and regenerated)

Fixed acids = sulfuric, phosphoric acids, B-hydroxybutyric acid and AOA, lactic acid, formic acid, glycolic acid, oxalic acid (etc).
- cant be expelled by the lungs and instead needs to be buffered by body fluids until excreted by kidneys

17

How do ATP and ADP work as buffers?

The phosphate groups on these molecules bind to H+ free ions

18

how does hemoglobin work as a buffer?

As blood flows through capillaries, O2 is released and hemoglobin -> deoxyhemoglobin

Deoxyhemoglobin accepts CO2 which gets converted into carbonic acid and H+/HCO3-. HCO3- leaves the red blood cell but the H+ gets buffered by binding to the hemoglobin

**primary reason behind why venous blood is only 0.03 lower in pH, despite having much larger amounts of CO2 than arterial blood**

19

What are the two ways that kidneys excrete fixed H+?

1) excretion of H+ bound to phosphate (H2PO4-)

2) excretion of H+ bound to NH3 (makes NH4+ which cant leave the renal lumen)

***both methods generate new HCO3- which is reabsorbed in the a-intercalated cells***
- this is to replenish the HCO3- that was used to buffer fixed acids

20

How do you measure the reabsoption rate of HC03-?

Filtered load of HCO3- = (GFR) x ( plasma concentration)
- under normal conditions = (180L/day) x (24mEq/L)= 4320

Excretion rate of HCO3- is almost always 2 mEq/day (except in pathology)

reabsorption rate = (filtered load) - (excretion rate)
- under normal situations = 4318 mEq/day

**the majority of this occurs in the PCT**

21

How does ECF expansion and contraction change bicarbonate reabsoption?

ECF volume expansion = inhibits HCO3- reabsorption

ECF volume contraction = promotes HCO3- reabsorption

**this and the function of angiotensin-2 on increasing Na/H+ channel activity explains why contraction alkalosis occurs (volume contraction automatically leads to acute metabolic alkalosis)**

22

How does PCO2 levels affect HCO3- levels?

Directly proportional

1) in metabolic acidosis, there is more H+ present in the blood and filtrate, which leads to increased Na+/H+ activity in the PCT cells.

2) this increase in activity causes higher levels of H+ to be in the lumen which promotes more carbonic acid formation and subsequent HCO3- reabsoption

23

Mechanism of excretion of titratable acid (H+ ions with urinary buffers (H2PO4- is msot common))

Excreted via a-intercalated cells of late DCT/CD
- use H+/ATPase channels (which are stimulated by aldosterone) and H+/K+/ATPase)

H+ that is secreted binds to free HPO3(2-) and forms titratable acid (H2PO4-) which is secreted

24

what prevents over excretion of H+ ions?

The pH of urine
- once the pH of urine hits 4.4, no more H+ will be secreted (due to acidic gradient preventing H+ from being pushed in)

**this is why it is important to have Phosphate, Bicarbonate and ammonium in the urine/filtrate since the presence fo these limits the speed at which the urine decreases form 7.4 -> 4.4**

25

What is the amount of fixed H+ production in the body from protein/phospholipid catabolism?

50 mEq/day
- 20 mEq/day = excreted via phosphate acid/ titratable acid
- 30 mEq/day = excreted via NH4+ ions

26

How does acidosis and hyperkalemia affect NH3+ generation?

Hyperkalemia
- inhibits NH3 synthesis and reduces ability to excrete H+ as NH4+

Acidosis
- promotes NH3 synthesis and increases ability to excrete H+ as NH4+

27

How does diabetic ketoacidosis and chronic renal failure change fixed H+ secretion?

Diabetic ketoacidosis
- increases total fixed H+ to 500 mEq/L a day
- causes increase glutamine metabolism and increased synthesis of NH3
- increases NH3 and titratable acid levels

Chronic renal failure
- normal levels of total fixed H+ (50mEq/L)
- decreased levels of phosphate buffer (since GFR is lowered) and impaired NH3 synthesis in PCT cells
- decreases levels of NH3 and titratable acid levels

28

Causes of increased anion gap metabolic acidosis

MUDPILES

M = methanol
U = uremia
D = Diabetic ketoacidosis
P = Propylene glycol
I = Iron tablets
L = lactic acidosis (ethanol OD)
E = ethylene glycol
S= Salicylate OD

29

Causes of normal anion gap metabolic acidosis

“HARDASS”

H = hyperchloremia
A = addisons/adrenal insufficiency
R = renal tubular acidosis
D = diarrhea
A = acetazolamide OD (Carbonic anhydrase Inhibtors)
S = Sprionolactone (K+ sparring)
S = Saline hyperinfusion

30

How does vomiting cause metabolic alkalosis

Gastric parietal cells produce H+ and HCO3- from carbonic anhydrase. HCO3- is reabsorbed and H+ is secreted out with Cl- to form HCL

Under normal nonvomoting conditions, normal HCL concentrations reach the small intestine (with food) and stimulate the originally reabsorbed HCO3- to get excreted but he pancreas back into the small intestine to neutralize the HCL
- this does NOT occur in vomiting, which in turn leads to loss of H+ (from vomiting HCL) and increase of HCO3-