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

MBBS I CPRS > L31 – Adaptation of Renal Mechanisms to Whole-Body Acid-Base Balance > Flashcards

Flashcards in L31 – Adaptation of Renal Mechanisms to Whole-Body Acid-Base Balance Deck (54):
1

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

net addition of acid to body

2

Why is pH maintenance necessary?

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

3

What is normal pH range?

7.38 - 7.42

4

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

5

How is acid level maintained for acid-base balance?

Amount of acid excreted = amount of acid produced

6

What is main chemical buffer for extracellular fluid?

Carbonic acid- bicarbonate buffer system

7

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

Inactivate excess acids and bases momentarily

8

Role of lungs and kidneys in acid base balance?

Eliminate acid in body

9

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-

10

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-

11

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

Proximal tubules in kidney

12

Amount of HCO3- absorption in PCT?

80% filtered HCO3-

13

What accompanies reabsorption of HCO3- in PCT in kidneys?

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

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?

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

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

15

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

CA-IV in the apical membrane

CA-II in intracellular space

16

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-

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?

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

18

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

19

What drives the movement of H+ - ATPase?

Using energy from ATP to pump H+ out of cell

20

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

21

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

amount of H+ excreted = amount of HCO3- reabsorbed

22

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

Ammoniagenesis

23

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

24

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

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

25

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

26

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

H+ and NH4+ have the same charge

27

What are the cell types in collecting duct?

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

28

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

29

What channels exist in IC-A?

Apical:
H+/K+ - ATPase
H+ - ATPase

Basolateral:
AE1 (HCO3-/ Cl- anion exchanger)

30

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

31

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

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

32

What are the channels in IC-B?

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

Basolateral: H+ ATPase

33

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

34

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

35

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

36

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

37

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+

38

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

39

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

40

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

41

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

42

How are K+, Ca2+ reabsorbed in PCT?

leaky tight junctions

43

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

NKCC

44

How does distal tubule mediate Na+ conc. ?

by aldosterone via Renin- angiotensin system

45

How are respiratory disorders compensated? Metabolic disorder compensation?

Respiratory disorder corrected by kidneys

Metabolic disorders corrected by Lungs

46

What are metabolic alkalosis / acidosis caused by?

Metabolic disease or abnormal renal function

47

What are repiratory acidosis/ alkalosis caused by?

acidosis = hypoventilation/ obstructive pulmonary diseases

alkalosis= hyperventilation

48

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

49

What are the 5 causes of metabolic acidosis?

HHRSD

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

50

What are the symptoms of metabolic acidosis?

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

Acidemia> coma >death

51

Define metabolic alkalosis.

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

52

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-

53

What are the 4 causes of metabolic alkalosis?

HHRP

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

54

Symptoms of metabolic alkalosis?

- Headache
- Compensatory Hypoventilation
- Arrhythmia
- Muscle weakness

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