Kidney Function 4

Question 1

How can you gain H+?

Answer 1

Hypoventilation - generation from CO2

Metabolism of protein and other organic molecules (non-volatile acids)

Due to loss of HCO3- in diarrhoea or other non-gastric fluids

Due to loss of HCO3- in urine

Question 2

How can you lose H+?

Answer 2

Hyperventilation - CO2 breathed out

Utilization of H+ in metabolism of various organic ions

Loss in vomitus

Loss in urine

Question 3

What is the normal range of plasma pH?

Answer 3

7.35-7.45

Question 4

What is the normal range of plasma [H+]?

Answer 4

35-45nM

Question 5

What process produces volatile acids?

Answer 5

Oxidative metabolism

Question 6

How are volatile acids excreted?

Answer 6

Via the lungs

Question 7

How are non-volatile acids excreted?

Answer 7

Via the kidneys

Question 8

What does a buffer consist of?

Answer 8

Mixture of a weak acid and its conjugate base

Question 9

What acts as a buffer in the blood?

Answer 9

HCO3-

Haemoglobin

Question 10

What acts as a buffer in interstitial fluid?

Answer 10

HCO3-

Question 11

What acts as a buffer in intracellular fluid?

Answer 11

Intracellular proteins

Phosphate

Question 12

What acts as a buffer in the urine?

Answer 12

Phosphate

Ammonia

Question 13

How does intracellular pH compare with plasma pH?

Answer 13

Lower (cytosol is 7.2)

Question 14

What organelle has a pH greater than plasma?

Answer 14

Mitochondria

Question 15

What is the Henderson-Hasselbalch equation?

Answer 15

pH = pK + log(CB/A)

Question 16

What does the effectiveness of a buffer depend on?

Answer 16

Concentration

pK

Question 17

What is normal arterial pCO2?

Answer 17

5.3kPa

Question 18

What is normal blood [HCO3-]?

Answer 18

25mM (higher in venous)

Question 19

How is acid-base balance achieved?

Answer 19

Matching output with input

Regulating the ratio of conjugate base to weak acid in buffer systems

Question 20

What is a big advantage of the HCO3- buffer in the blood?

Answer 20

Addition of H+ causes pCO2 to rise

Drives ventilation to increase elimination of CO2

Question 21

What is the normal pH range of urine?

Answer 21

4.4 - 8

Question 22

What could cause you to have alkaline urine (environmental factor)?

Answer 22

No protein in diet

Question 23

Why is a urine pH below 4.4 dangerous?

Answer 23

Tubule transporters cannot function

Question 24

Where is HCO3- reabsorbed in the nephron?

Answer 24

80% in PCT

10-15% in loop of Henle

Remainder in cortical collecting ducts

Question 25

Which cells reabsorb HCO3- in the cortical collecting duct?

Answer 25

Intercalated cells type A

Question 26

What enzyme catalyses the formation of carbonic acid from water and CO2?

Answer 26

Carbonic anhydrase (isoform 2 in cytosol, 4 in luminal membrane)

Question 27

What transporters are involved in H+ secretion?

Answer 27

Na/H exchanger NHE3 H-ATPase pump H/K-ATPase pump

Question 28

When is the H+ secreted not excreted and why?

Answer 28

When HCO3- is present in the lumen Combines and CO2 moves back passively (water reabsorbed if aquaporins present)

Question 29

How is H+ excreted in the kidneys?

Answer 29

All HCO3- reabsorbed first In combination with nonbicarbonate buffers - monohydrogen phosphate Glutamine metabolism produces ammonium ions which are secreted via the Na/NH4 exchanger

Question 30

How does glutamine enter the tubule epithelium?

Answer 30

Freely filtered at renal corpuscle LAT2 glutamine amino acid exchanger

Question 31

What three mechanisms help maintain a constant pH and what are their timescales?

Answer 31

Chemical buffers - seconds Brainstem respiratory centre - minutes Renal mechanisms - hours to days

Question 32

What is pH proportional to?

Answer 32

[HCO3-]/pCO2

Question 33

What is compensation?

Answer 33

The body's attempt to return the pH to normal in response to a primary acid/base disorder

Question 34

What is respiratory acidosis?

Answer 34

Insufficient CO2 excretion by lungs

Question 35

What can cause acute respiratory acidosis?

Answer 35

Drug-induced respiratory depression (eg. narcotics, barbituates) Airway obstruction (eg. asthma)

Question 36

What can cause chronic respiratory acidosis?

Answer 36

Airway obstruction (eg. COPD) Lung damage (eg. fibrosis) Chest wall disorders (eg. pectus carinatum) Neuromuscular disorders (eg. amyotrophic lateral sclerosis)

Question 37

What are the responses to respiratory acidosis?

Answer 37

Some of the retained CO2 is converted to HCO3- in plasma (increase buffering) Increased H+ secretion and glutamine metabolism in kidneys to increase HCO3- in plasma

Question 38

What is metabolic acidosis?

Answer 38

Fall in plasma [HCO3-]

Question 39

What are examples of a true HCO3- deficit/normal anion gap?

Answer 39

Renal tubular acidosis as kidneys cannot reabsorb Diarrhoea (GI)

Question 40

What are examples of a H+ gain/increased anion gap?

Answer 40

Intake of exogenous acid - NH4Cl, toxins Abnormal lipid metabolism - diabetic ketoacidosis Abnormal carbohydrate metabolism - lactic acidosis Normal protein metabolism with nephron damage - uremic acidosis

Question 41

What are the responses to metabolic acidosis?

Answer 41

Buffering causes increased pCO2 therefore increased ventilation Increased H+ secretion and glutamine metabolism in kidneys to increase plasma [HCO3-]

Question 42

What can cause respiratory alkalosis?

Answer 42

Excessive central respiratory drive: - Aspirin overdose - Fever - Brainstem damage Hypoxic stimulation: - Altitude - Hysteric hyperventilation - Pulmonary embolism

Question 43

What is the response to respiratory alkalosis?

Answer 43

Reduce ventilation if possible Reduced H+ secretion so not all HCO3- reabsorbed (alkaline urine)

Question 44

What can cause metabolic alkalosis?

Answer 44

Repeated vomiting Excess aldosterone (stimulates H-ATPase) Excess alkali ingestion (HCO3- or citrate/lactate)

Question 45

What is the response to metabolic alkalosis?

Answer 45

pH change inhibits ventilation so more CO2 retained (more H+ formed) but hypoxia will stimulate breathing Kidneys excrete more HCO3- as there is less H+ available for reabsorption

Question 46

What becomes active in the collecting duct during metabolic alkalosis?

Answer 46

Type B intercalated cells with pendrin (HCO3-/Cl- exchanger)

Question 47

How is blood pH associated with plasma potassium concentration?

Answer 47

Increased blood pH associated with hypokalaemia Decreased blood pH associated with hyperkalaemia

Question 48

Why is acidosis associated with hyperkalaemia?

Answer 48

Acidosis inhibits K+ secretion K+ secretion depends on membrane potential which is altered by increased H+ in lumen (more positive)

Question 49

How does acidosis affect liver glutamine metabolism?

Answer 49

Increases

Question 50

How does alkalosis affect liver glutamine metabolism?

Answer 50

Decreases