L31 – Adaptation of Renal Mechanisms to Whole-Body Acid-Base Balance

Question 1

Net addition of acid of alkaline to body after typical diet consumption?

Answer 1

net addition of acid to body

Question 2

Why is pH maintenance necessary?

Answer 2

Proper organ and cellular function depends on enzyme activity - sensitive to pH

Question 3

What is normal pH range?

Answer 3

7.38 - 7.42

Question 4

Components of typical diet that can cause net increase in acid?

Answer 4

Protein metabolism> strong acids (e.g. H2SO4 from cysteine residue breakdown)

Fatty acid metabolism > Ketone bodies (e.g. acetoacetate)

Glucose> anaerobic resp. = lactate or aerobic resp. = CO2

Question 5

How is acid level maintained for acid-base balance?

Answer 5

Amount of acid excreted = amount of acid produced

Question 6

What is main chemical buffer for extracellular fluid?

Answer 6

Carbonic acid- bicarbonate buffer system

Question 7

What is the function of carbonic acid - bicarbonate buffer system?

Answer 7

Inactivate excess acids and bases momentarily

Question 8

Role of lungs and kidneys in acid base balance?

Answer 8

Eliminate acid in body

Question 9

Difference between lungs and kidneys function in maintaining acid- base balance by acid removal?

Answer 9

Lungs = fast removal of only volatile acids (CO2)

Kidneys = slow removal of non-volatile acids (e.g.ketone bodies) , reabsorb or synthesize HCO3-

Question 10

What can the renal system eliminate but not the lungs in maintaining acid- base balance?

Answer 10

Renal can:
1) remove non-volatile acids (e.g. uric acid, ketone bodies, lactic acids)

2) regulate alkaline by removing HCO3-
3) Restore chemical buffers to manage H+ in ECF by making or reabsorption of HCO3-

Question 11

What is the first site to perform acid-base balance in body?

Answer 11

Proximal tubules in kidney

Question 12

Amount of HCO3- absorption in PCT?

Answer 12

80% filtered HCO3-

Question 13

What accompanies reabsorption of HCO3- in PCT in kidneys?

Answer 13

Equal amount of H+ secreted into filtrate to amount of HCO3- reabsorbed from filtrate

Question 14

What are the channels on apical and basolateral membranes for absorption of HCO3- and H+ secretion in PCT in kidney? What is the 4th channel not used for H+ or HCO3- directly?

Answer 14

Basolateral membrane= HCO3- reabsorption =
Na+/HCO3- cotransporter
Na+/K+ ATPase

Apical membrane = H+ secretion =
H+ - ATPase
Na+/H+ exchanger (NHE)

Question 15

What are the two types of Carbonic anhydrase in the PCT cells?

Answer 15

CA-IV in the apical membrane

CA-II in intracellular space

Question 16

What is the function of the two CA in PCT cells in kidneys?

Answer 16

CA-IV for production of H2O & CO2:
conversion of H2CO3 to H2O and CO2 at apical membrane > H2O and CO2 diffuse into cell

CA-II for generation of h+ & HCO3- :
conversion of intracellular CO2 and H2O back into H2CO3, which then dissociates to H+ & HCO3-

Question 17

The three channels in the PCT for H+ and HCO3- transport belong to which types of active transport? What about the 4th channel on basolateral membrane not directly used for H+ & HCO3- transport?

Answer 17

Basolateral membrane: Na+/HCO3- co-transporter is symport = secondary active transport

Apical membrane:
H+ - ATPase is primary active transport

Na+ / H+ exchanger NHE is secondary active transport/ antiport

4th channel = Na+/K+ ATPase is primary active transport

Question 18

What drives the movement of NHE pump in PCT cells? (Start with a certain channel)

Answer 18

Na+/K+ ATPase at basolateral membrane uses energy to pump Na+ into Interstitial fluid >

Depletion of Na+ in PCT cell creates Na+ concentration gradient across cell membrane>

Na+ moves into cell from filtrate, driving NHE to move H+ out of cell

Question 19

What drives the movement of H+ - ATPase?

Answer 19

Using energy from ATP to pump H+ out of cell

Question 20

How is HCO3- reabsorbed in to blood?

Answer 20

HCO3- inside PCT cell (after action of CA-II and CA-IV…) moves through basolateral membrane by Na+/HCO3- symport channel

Question 21

Ratio of H+ secreted and HCO3- reabsorbed in PCT of kidneys?

Answer 21

amount of H+ excreted = amount of HCO3- reabsorbed

Question 22

What is the main process for generating new HCO3- in PCT of kidneys?

Answer 22

Ammoniagenesis

Question 23

Explain how glutamine moves into PCT in kidneys?

Answer 23

Glutamine moves into PCT cell by either:

• SN1 glutamine transporter at basolateral membrane from interstitial fluid
• Na+/Glutamine cotransporter at apical membrane from filtrate

Question 24

How is glutamine used to make new HCO3- in PCT in kidneys?

Answer 24

1 Glutamine > ammoniagenesis > 2 NH4+ and 2HCO3-

Question 25

What happens to the products of amminogenesis in PCT of kidneys?

Answer 25

Glutamine > NH4+ + HCO3- NH4+ exits cell via apical NHE channel to filtrate HCO3- exits cell via basolateral Na+/HCO3- symport channel to interstitial fluid

Question 26

How come NH4+ can exit the apical membrane via the NHE, which is used for H+?

Answer 26

H+ and NH4+ have the same charge

Question 27

What are the cell types in collecting duct?

Answer 27

``` Principal cells (PC) Intercalated cells (IC) type A & B ```

Question 28

What are the roles of IC-A and IC-B in collecting duct? Role of PC?

Answer 28

IC-A: secrete H+ and NH3 (acid) IC-B: secrete HCO3- (base) PC: water reabsorption by responding to Vp

Question 29

What channels exist in IC-A?

Answer 29

Apical: H+/K+ - ATPase H+ - ATPase Basolateral: AE1 (HCO3-/ Cl- anion exchanger)

Question 30

How does IC-A secrete H+? (start with H2O and CO2 inside IC-A)

Answer 30

H20 + CO2 > H2CO3 > H+ + HCO3- H+ transported through apical membrane by H+ - ATPase and H+/K+ ATPase HCO3- transported by basolateral anion exachanger AE1

Question 31

Whats the ratio of anion exchange at basolateral membrane of IC-A?

Answer 31

Amount of Cl- in = amount of HCO3- out into interstitial fluid

Question 32

What are the channels in IC-B?

Answer 32

Apical: Pendrin (HCO3- / Cl- anion exchanger) Basolateral: H+ ATPase

Question 33

Explain how hypochloremia can cause alkalosis. (Always remember hypochloremia > pendrin)

Answer 33

Hypochloremia = low [Cl-] In IC-B, movement of HCO3- out of IC-B into filtrate depends on HCO3-/Cl- anion exchanger- Pendrin Pendrin depends on conc. grad., not ATP low [Cl-] in FILTRATE= decreased conc. gradient = decreased movement of Cl- to drive secretion of HCO3- into interstitial fluid HCO3- accumulates > alkalosis

Question 34

Explain the difference in mitochondria distribution between IC-A and IC-B?

Answer 34

IC-A: apical membrane has both H+ ATPase and H+/K+ ATPase. Both use ATP so mitochondria cluster at apical membrane IC-B: basolateral membrane has H+ - ATPase so more mitochondria cluster at basolateral membrane

Question 35

What are the channels for NH3 transport in collecting tube?

Answer 35

IC-A apical membrane: Rhcg Rhesus glycoprotein ammonia transporter IC- A basolateral membrane: Na+/K+ ATPase used for NH4+ transport

Question 36

Explain ammonia movement in IC-A.

Answer 36

Basolateral: NH3 enter via Na+/K+ ATPase from interstitial fluid to cytoplasm> Apical: NH3 diffuse out into filtrate or through Rhcg channel

Question 37

How is the Renin- angiotensin system activated and what is effect on K?

Answer 37

Low [Na+] detected at distal tubules > | Renin secreted > increase angiotensin and aldosterone conc. > increase Na+ reabsoprtion by excreting K+

Question 38

How does too much aldosterone cause alkalosis? (think K, IC-A channel...)

Answer 38

Hyperaldosteronism > increase Na+ reabsorption by increasing K+secretion > Hypokalemia = low [K+] > H+/K+ ATPase at IC-A tries to compensate by increasing absorption of K+ and secreting H+ > [H+] drops > alkalosis

Question 39

How does Hyperkalemia cause acidosis? (think NH4+, channel...)

Answer 39

Hyperkalemia > since NH4+ and K+ both rely on Na+/K+ ATPase at IC-A basolateral membrane > increase [K+] competes with NH4+ at channel > less NH4+ able to be secreted > H+ not titrated in filtrate and [H+] increases > acidosis

Question 40

Why is luminal NH3 so important at collecting ducts?

Answer 40

NH3 in filtrate can titrate H+ to form NH4+ in urine (neutralize urine and protect urinary organs) NH3 titrating H+ can maintain low filtrate [H+] > further H+ secretion

Question 41

What are the two differences between the NH3 secreted at PCT vs collecting duct?

Answer 41

PCT: NH3 made from Glutamine via ammoniagenesis (by product is HCO3-) Collecting duct: NH3 extracted from interstitial fluid PCT: transport via NHE channel into filtrate Collecting duct: transport via diffusion or Rhcg

Question 42

How are K+, Ca2+ reabsorbed in PCT?

Answer 42

leaky tight junctions

Question 43

What channel creates osmotic gradient in asending limb of Loop of Henle?

Answer 43

NKCC

Question 44

How does distal tubule mediate Na+ conc. ?

Answer 44

by aldosterone via Renin- angiotensin system

Question 45

How are respiratory disorders compensated? Metabolic disorder compensation?

Answer 45

Respiratory disorder corrected by kidneys Metabolic disorders corrected by Lungs

Question 46

What are metabolic alkalosis / acidosis caused by?

Answer 46

Metabolic disease or abnormal renal function

Question 47

What are repiratory acidosis/ alkalosis caused by?

Answer 47

acidosis = hypoventilation/ obstructive pulmonary diseases alkalosis= hyperventilation

Question 48

Definition of metabolic acidosis?

Answer 48

- Excessive accumulation of non-volatile acid - manifested as a primary reduction of serum bicarbonate concentration in body - associated with low plasma pH

Question 49

What are the 5 causes of metabolic acidosis? HHRSD

Answer 49

- Hyperkalemia - Renal failure - Severe diarrhea and loss of HCO3- from GIT - Hypoxia or sepsis-induced lactic acidosis - Diabetes melitus-induced ketoacidosis

Question 50

What are the symptoms of metabolic acidosis?

Answer 50

- Headache - Compensatory hyperventilation - Fatigue - Raised HR - Fruity smell (Diabetes- induced ketoacidosis) - Osteoporosis Acidemia> coma >death

Question 51

Define metabolic alkalosis.

Answer 51

Acid-base disorder in which plasma HCO3- rise at higher than expected level

Question 52

What 2 processes are involved in pathogenesis of metabolic alkalosis?

Answer 52

Generation and maintenance of metabolic acidosis Making too much HC03- and not being able to remove enough HCO3-

Question 53

What are the 4 causes of metabolic alkalosis? HHRP

Answer 53

- Hyperchloremia (pendrin ...etc) - Hypokalemia - Renal failure - Prolonged vomiting (loss of H+ from stomach)

Question 54

Symptoms of metabolic alkalosis?

Answer 54

- Headache - Compensatory Hypoventilation - Arrhythmia - Muscle weakness