Kidney Function: Regulation of Osmolarity, Blood Volume and Acid-Base Balance

Question 1

What is the main determinant of extracellular fluid volume?

Answer 1

Total quantity of solute (mainly Na+Cl-).

Regulation of ECF volume is based on sodium balance.

Question 2

How is Na+ regulated?

Answer 2

By the kidney via:
- Glomerular filtration rate
- Sodium reabsorption
Sodiume excreted in urine = sodium filtered - sodium reabsorbed

Question 3

How is GFR extrinsically controlled?

Answer 3

If baroreceptors detect low blood pressure - activates sympathetic nervous system.
- Constricts afferent arteriole
- Reduces surface area (mesangial cells contract)
Overall decreases GFR. Conserves sodium and water and increases blood volume/pressure.

Question 4

How is GFR intrinsically controlled?

Answer 4

Autoregulation in the kidney controls afferent arteriole constriction.

• Myogenic response by renal smooth muscle.
• Tubularglomerular feedback by juxtaglomerular apparatus.

Question 5

How is renin secretion stimulated?

Answer 5

Sympathetic nerves of granular cells recive signals from baroreceptors - causes extrinsic controlled release of renin.
May also be released by reduction in sodium delivery to the maculla densa.

Question 6

What is the function of renin?

Answer 6

Ultimately causes an increase in blood pressure.
Catalyses conversion of plasma angiotensinogen to Angiotensin 1.
Angiotensin I > Angiotensin II

Question 7

What are the actions of angiotensin II?

Answer 7

1. Stimulates proximal tubule na+ reabsorption by Na+/H+ exchanger and Na+K+ATPase.
2. Stimulates ADH release and causes thirst.
3. Causes aldosterone secretion - increases sodium reabsorption (stimulates Na+K+ATPase)

Question 8

What are natriuretic peptides?

Answer 8

Released when the heart is stretched due to high blood pressure.
A-type = from atrial myocardium (ANP)
B-type = from ventricular myocardium (BNP)

Question 9

What is the function of naturetic peptides?

Answer 9

Acts on collecting ducts to inhibit Na+ entry into epithelium.
Inhibits renin release.
Increases excretion of Na+.
Decreases blood pressure.

Question 10

What is the equation of the acid-base balance in the kidney?

Answer 10

CO2 + H2O > HCO3 > HCO3- + H+

Both reactions are reversible.

Question 11

What are some causes of hydrogen ion gain in the body?

Answer 11

• Generation from CO2 and H2O.
• Production of non-volatile acids from the metabolism of protein and other organic molecules.
• Gain of hydrogen ions due to loss of bicarbonate in diarrhoea.

Question 12

What are some causes of hydrogen ion loss in the body?

Answer 12

• Utilisation of hydrogen ions in the metabolism of various organic anions.
• Loss of hydrogen ions in votmit/urine
• Hyperventilation

Question 13

What is the most important buffer in the body?

Answer 13

Bicarbonate buffer system

HCO3- + H+ > H2CO3

Question 14

What is the Hendellson-Haselbalch equation?

Answer 14

pH = pKa + (log[HCO3-])/[H2CO3]

Buffer effectiveness depends on its concentration and pH

Question 15

What is normal arterial pH?

Answer 15

pH 7.4 (7.35-7.45)

Question 16

What is normal arteral [HCO3-]?

Answer 16

25mM (19-24)

Question 17

What is normal venous [HCO3-]?

Answer 17

25mM (22-28)

Question 18

What is normal partial pressure of arterial CO2?

Answer 18

5.3kPa (4.0-6.kPa)

Question 19

What two factors effect pH?

Answer 19

[HCO3-] (dealt with by kidney)

[pCO2] (dealth with by lungs)

Question 20

Where does bicarbonate reabsorption occur in the kidney?

Answer 20

Proximal tubule (80%)
Ascending Loop of Henle (10-15%)
Cortical collecting ducts (intercalated cells type A)

Question 21

How does bicarbonate absorption occur in the nephron?

Answer 21

Carbonic anhydrase in epithelial cells converts H2O +CO2 > HCO3- + H+
H+ enters tubular lumen and combines with HCO3- to form H2CO3. Which breaks into H2O and CO2 for reabsorption.
HCO3- produced in the epithelial cells is pumped into the interstitial fluid.

Question 22

How does H+ excretion occur in the kidney?

Answer 22

Same mechanism as bicarbonate absorption but instead H+ moves into tubule and reacts with HPO4(2-) to form H2PO4- which is excreted.

Question 23

How is HCO3- added to plsma using glutamine?

Answer 23

Glutamine enters tubule epithelium via Na+ co-transporter.
Glutamine is metabolism in the tubule epithelium releasing NH4+ and HCO3-.
NH4+ enters lumen and is excreted.
HCO3- enters capillary.

Question 24

What are the 3 regulatory systems of acid-base status?

Answer 24

1. Chemical buffers - act in seconds. Bicarbonate, phosphate.
2. Brainstem respiratory centre - responds to changes in pCO2, pO2 and [H+]. Ajusts ventilation to reatin or expel CO2.
3. Renal mechanisms - H+ and HCO3-

Question 25

What define acidosis and alkalosis?

Answer 25

Acidosis - plasma pH < 7.35

Alkalosis - plasma pH >7.45

Question 26

Name the two types of acid-base disorder.

Answer 26

Respiratory alkalosis/acidosis

Metabolic alkalosis/acidosis

Question 27

What causes respiratory acidosis?

Answer 27

Caused by insufficient CO2 excretion by the lungs (alveolar hypoventilation)

Question 28

What are the two types of respiratory acidosis?

Answer 28

Acute: PaCO2 >5.3     kPa: pH<7.5
- abrupt failure in ventilation
- drug induced respiratory depression
- airway obstruction
Chronic: PaCO2>5.3   kPa: pH<7.35  
- HCO3>30mM
- Secondary to many disorders:
- COPD, fibrosis (lung damage), chest wall disorders, neuromuscular disorders.

Question 29

What is the body’s response to respiratory acidosis?

Answer 29

1. Chemical buffers: CO2 +H2O > H2CO3 > HCO3- + H+. Plasma HCO3- increases.
2. Brainstem respiratory centre - has no effect as ventilation is the primary issue.
3. Renal mechanisms - for each H+ secreted, HCO3- is reabsorbed. Excrete acid in the form of ammonia.

Question 30

What are the two types of metabolic acidosis?

Answer 30

True bicarbonate deficit:
- kidney = renal tubular acidosis
- gastrointestinal = diarrhoea
H+ gain:
- Exogenous acid = NH4Cl administration, toxins.
- Abnormal lipid metabolism = diabetic ketosis
- Abnormal carbohydrate metabolism = lactic acidosis
- Normal protein metabolism = uremic acidosis

Question 31

What is the body’s response to metabolic acidosis?

Answer 31

1. Chemical buffer - H+ + HCO3- > H2O + CO2
2. Brainstem respiratory system - increase ventilation to expel CO2.
3. Renal compensation - glutamin metabolism

Question 32

What is respiratory alkalosis caused by?

Answer 32

Excessive central respiratory drive or hypoxic stimulation.

Excess CO2 is lost in lungs, pCO2 falls.

Question 33

How does the body respond to respiratory alkalosis?

Answer 33

1. Chemical buffers - [HCO3-] decreases as it reacts with H+.
2. Respiratory - reduce ventilation
3. Renal mechanisms - reduction of H+ secretion into tubules.

Question 34

What causes metabolic alkalosis?

Answer 34

Repeated vomiting - loss of gastric acid
Excess aldosterone - stimulates tubule H+/ATPasepump
Excess alkali ingestion - bicarbonate or citrate/lactate which are metabolised to bicarbonate.