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

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Flashcards in L31 – Adaptation of Renal Mechanisms to Whole-Body Acid-Base Balance Deck (54):

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

net addition of acid to body


Why is pH maintenance necessary?

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


What is normal pH range?

7.38 - 7.42


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

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


How is acid level maintained for acid-base balance?

Amount of acid excreted = amount of acid produced


What is main chemical buffer for extracellular fluid?

Carbonic acid- bicarbonate buffer system


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

Inactivate excess acids and bases momentarily


Role of lungs and kidneys in acid base balance?

Eliminate acid in body


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

Lungs = fast removal of only volatile acids (CO2)

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


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

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-


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

Proximal tubules in kidney


Amount of HCO3- absorption in PCT?

80% filtered HCO3-


What accompanies reabsorption of HCO3- in PCT in kidneys?

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


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?

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

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


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

CA-IV in the apical membrane

CA-II in intracellular space


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

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-


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?

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


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

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


What drives the movement of H+ - ATPase?

Using energy from ATP to pump H+ out of cell


How is HCO3- reabsorbed in to blood?

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


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

amount of H+ excreted = amount of HCO3- reabsorbed


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



Explain how glutamine moves into PCT in kidneys?

Glutamine moves into PCT cell by either:
-SN1 glutamine transporter at basolateral membrane from interstitial fluid
-Na+/Glutamine cotransporter at apical membrane from filtrate


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

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


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

Glutamine > NH4+ + HCO3-

NH4+ exits cell via apical NHE channel to filtrate

HCO3- exits cell via basolateral Na+/HCO3- symport channel to interstitial fluid


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

H+ and NH4+ have the same charge


What are the cell types in collecting duct?

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


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

IC-A: secrete H+ and NH3 (acid)
IC-B: secrete HCO3- (base)

PC: water reabsorption by responding to Vp


What channels exist in IC-A?

H+/K+ - ATPase
H+ - ATPase

AE1 (HCO3-/ Cl- anion exchanger)


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

H20 + CO2 > H2CO3 > H+ + HCO3-

H+ transported through apical membrane by H+ - ATPase and H+/K+ ATPase

HCO3- transported by basolateral anion exachanger AE1


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

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


What are the channels in IC-B?

Apical: Pendrin (HCO3- / Cl- anion exchanger)

Basolateral: H+ ATPase


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

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


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

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


What are the channels for NH3 transport in collecting tube?

IC-A apical membrane: Rhcg
Rhesus glycoprotein ammonia transporter

IC- A basolateral membrane:
Na+/K+ ATPase used for NH4+ transport


Explain ammonia movement in IC-A.

Basolateral: NH3 enter via Na+/K+ ATPase from interstitial fluid to cytoplasm>

Apical: NH3 diffuse out into filtrate or through Rhcg channel


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

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


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

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


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

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


Why is luminal NH3 so important at collecting ducts?

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


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

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


How are K+, Ca2+ reabsorbed in PCT?

leaky tight junctions


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



How does distal tubule mediate Na+ conc. ?

by aldosterone via Renin- angiotensin system


How are respiratory disorders compensated? Metabolic disorder compensation?

Respiratory disorder corrected by kidneys

Metabolic disorders corrected by Lungs


What are metabolic alkalosis / acidosis caused by?

Metabolic disease or abnormal renal function


What are repiratory acidosis/ alkalosis caused by?

acidosis = hypoventilation/ obstructive pulmonary diseases

alkalosis= hyperventilation


Definition of metabolic acidosis?

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


What are the 5 causes of metabolic acidosis?


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


What are the symptoms of metabolic acidosis?

-Compensatory hyperventilation
- Raised HR
- Fruity smell (Diabetes- induced ketoacidosis)

Acidemia> coma >death


Define metabolic alkalosis.

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


What 2 processes are involved in pathogenesis of metabolic alkalosis?

Generation and maintenance of metabolic acidosis

Making too much HC03- and not being able to remove enough HCO3-


What are the 4 causes of metabolic alkalosis?


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


Symptoms of metabolic alkalosis?

- Headache
- Compensatory Hypoventilation
- Arrhythmia
- Muscle weakness

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