Kidney Function: Regulation of Osmolarity, Blood Volume and Acid-Base Balance Flashcards
What is the main determinant of extracellular fluid volume?
Total quantity of solute (mainly Na+Cl-).
Regulation of ECF volume is based on sodium balance.
How is Na+ regulated?
By the kidney via:
- Glomerular filtration rate
- Sodium reabsorption
Sodiume excreted in urine = sodium filtered - sodium reabsorbed
How is GFR extrinsically controlled?
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.
How is GFR intrinsically controlled?
Autoregulation in the kidney controls afferent arteriole constriction.
- Myogenic response by renal smooth muscle.
- Tubularglomerular feedback by juxtaglomerular apparatus.
How is renin secretion stimulated?
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.
What is the function of renin?
Ultimately causes an increase in blood pressure.
Catalyses conversion of plasma angiotensinogen to Angiotensin 1.
Angiotensin I > Angiotensin II
What are the actions of angiotensin II?
- Stimulates proximal tubule na+ reabsorption by Na+/H+ exchanger and Na+K+ATPase.
- Stimulates ADH release and causes thirst.
- Causes aldosterone secretion - increases sodium reabsorption (stimulates Na+K+ATPase)
What are natriuretic peptides?
Released when the heart is stretched due to high blood pressure.
A-type = from atrial myocardium (ANP)
B-type = from ventricular myocardium (BNP)
What is the function of naturetic peptides?
Acts on collecting ducts to inhibit Na+ entry into epithelium.
Inhibits renin release.
Increases excretion of Na+.
Decreases blood pressure.
What is the equation of the acid-base balance in the kidney?
CO2 + H2O > HCO3 > HCO3- + H+
Both reactions are reversible.
What are some causes of hydrogen ion gain in the body?
- 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.
What are some causes of hydrogen ion loss in the body?
- Utilisation of hydrogen ions in the metabolism of various organic anions.
- Loss of hydrogen ions in votmit/urine
- Hyperventilation
What is the most important buffer in the body?
Bicarbonate buffer system
HCO3- + H+ > H2CO3
What is the Hendellson-Haselbalch equation?
pH = pKa + (log[HCO3-])/[H2CO3]
Buffer effectiveness depends on its concentration and pH
What is normal arterial pH?
pH 7.4 (7.35-7.45)
What is normal arteral [HCO3-]?
25mM (19-24)
What is normal venous [HCO3-]?
25mM (22-28)
What is normal partial pressure of arterial CO2?
5.3kPa (4.0-6.kPa)
What two factors effect pH?
[HCO3-] (dealt with by kidney)
[pCO2] (dealth with by lungs)
Where does bicarbonate reabsorption occur in the kidney?
Proximal tubule (80%) Ascending Loop of Henle (10-15%) Cortical collecting ducts (intercalated cells type A)
How does bicarbonate absorption occur in the nephron?
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.
How does H+ excretion occur in the kidney?
Same mechanism as bicarbonate absorption but instead H+ moves into tubule and reacts with HPO4(2-) to form H2PO4- which is excreted.
How is HCO3- added to plsma using glutamine?
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.
What are the 3 regulatory systems of acid-base status?
- Chemical buffers - act in seconds. Bicarbonate, phosphate.
- Brainstem respiratory centre - responds to changes in pCO2, pO2 and [H+]. Ajusts ventilation to reatin or expel CO2.
- Renal mechanisms - H+ and HCO3-
What define acidosis and alkalosis?
Acidosis - plasma pH < 7.35
Alkalosis - plasma pH >7.45
Name the two types of acid-base disorder.
Respiratory alkalosis/acidosis
Metabolic alkalosis/acidosis
What causes respiratory acidosis?
Caused by insufficient CO2 excretion by the lungs (alveolar hypoventilation)
What are the two types of respiratory acidosis?
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.
What is the body’s response to respiratory acidosis?
- Chemical buffers: CO2 +H2O > H2CO3 > HCO3- + H+. Plasma HCO3- increases.
- Brainstem respiratory centre - has no effect as ventilation is the primary issue.
- Renal mechanisms - for each H+ secreted, HCO3- is reabsorbed. Excrete acid in the form of ammonia.
What are the two types of metabolic acidosis?
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
What is the body’s response to metabolic acidosis?
- Chemical buffer - H+ + HCO3- > H2O + CO2
- Brainstem respiratory system - increase ventilation to expel CO2.
- Renal compensation - glutamin metabolism
What is respiratory alkalosis caused by?
Excessive central respiratory drive or hypoxic stimulation.
Excess CO2 is lost in lungs, pCO2 falls.
How does the body respond to respiratory alkalosis?
- Chemical buffers - [HCO3-] decreases as it reacts with H+.
- Respiratory - reduce ventilation
- Renal mechanisms - reduction of H+ secretion into tubules.
What causes metabolic alkalosis?
Repeated vomiting - loss of gastric acid
Excess aldosterone - stimulates tubule H+/ATPasepump
Excess alkali ingestion - bicarbonate or citrate/lactate which are metabolised to bicarbonate.
