Regulation of homeostasis by the kidney Flashcards
What are the 2 roles of the kidney in homeostasis?
(1)Role of the kidney in volume regulation
Fluid balance: The amount of water gained by the body each day equals the amount lost
Electrolyte balance: The ion gain each day equals ion loss
(2) Control of acid-base balance by the kidneys
Acid-base balance: H+ gain is offset by H+ loss
What is the normal pH range of arterial blood?
What is the survival pH range?
What are the consequences of pH outside of 7.35-7.45?
- If plasma levels fall below 7.35 (acidaemia), acidosis results
- If plasma levels rise above 7.45 (alkalaemia), alkalosis results
Alterations outside these boundaries affects all body systems
- Can result in coma, cardiac failure and circulatory collapse
- At pH < 6.8 or > 8.0 death occurs
Define acid, base and how they’re grouped
Acids
- Release H+ into solution
Bases
- Remove H+ from solution
Acids and bases
- Grouped as strong or weak
What is pH?
pH = potential of hydrogen: specifies acidity or basicity of an aqueous solution
Define buffer
What are the 3 buffer systems in the body?
Buffers: Resist changes in pH
- When H+ added, buffer removes it
- When H+ removed, buffer replaces it
Types of buffer systems
- Carbonic acid/bicarbonate
- Protein
- Phosphate
Why must the kidneys maintain acid-base homeostasis?
•This is important because all biochemical processes must occur within an optimal pH window (pH 7.2 - 7.4)
Write the acid-base homeostasis equation
What are the sources of acid in the body?
- The lungs excrete a large amount of CO2 – this is a potential acid formed by metabolism (CO2 reacts with water to form carbonic acid)
- The kidneys also secrete and excrete non-volatile acids produced from normal metabolism, e.g. lactic acid, which the lungs can’t excrete
How is the production of acid countered?
- HOWEVER, to maintain acid-base balance, the kidneys must also reabsorb virtually all filtered HCO3-
- This is important as HCO3- acts as a physiological buffer
- This control of acid-base balance prevents ACIDOSIS or ALKALOSIS
What is the equation for pH?
- Blood pH = ____
- Urine pH ____
- Blood [HCO3-] = _____ mM
- Blood pCO2 = partial pressure of CO2 = _____ mmHg
- Plasma osmolality = _____ mOsm/kg water
Urine osmolality = _____ mOsm/kg water
- Blood pH = 7.4
- Urine pH ~ 6.0
- Blood [HCO3-] = 24 mM
- Blood pCO2 = partial pressure of CO2 = 40 mmHg
- Plasma osmolality = 285 mOsm/kg water
Urine osmolality = 600 mOsm/kg water
What does urine osmolalilty depend on?
(but urine osmolality depends upon hydration status –
it can vary between 50-1200 mOsm/kg, e.g. depending on fluid intake)
What is the The relationship between
pH, HCO3- and CO2?
Inverse relationship between pH and plasma concentration of CO2
i.e. when one goes up the other goes down and vice versa…….
So when pCO2 increases, e.g. in COPD, pH decreases (acidosis) as CO2 reacts with water to form carbonic acid
How does respiratory regulation of acid-base balance work?
Respiratory regulation of pH is achieved via the HCO3-/CO2 (carbonic acid) buffer system:
- as pCO2 levels increase, pH decreases
- as pCO2 levels decrease, pH increases
Changes in pH levels are detected by peripheral chemoreceptors
These then act on respiration centres in the brain to adjust respiration rates:
How does renal regulation of acid-base balance work?
•Most HCO3- in filtrate is reabsorbed, H+ is also secreted
(pH urine ~ 6.0). “Renal tubular acidosis (RTA)” may occur if the kidneys don’t do this effectively, e.g. in renal failure
- If pH of ECF falls (acidaemia): more secretion of H+ into filtrate AND reabsorption of HCO3- back into ECF cause pH to increase
- Secretion of H+ inhibited when urine pH falls below 4.5
- If pH of ECF increases (alkalaemia): secretion of H+ into filtrate and reabsorbtion of HCO3- declines. Extracellular pH decreases
What is the most efficient regulator of acid-base balance?
Kidneys
What is the kidneys response to acidaemia?
we want to increase (1) H+ secretion and
(2) HCO3- reabsorption and (3) HCO3- generation in the Distal Tubule & CD (Intercalated Cells)
What is acidosis?
Acidosis: pH of body fluids falls below 7.35
Too much H+. Solution: Get rid of H+ out of the body:
(i) Excrete it via the lungs (as CO2) and the kidneys (as H+)
(ii) Generate more buffer (HCO3-) in the kidneys
What is alkalosis?
Alkalosis: pH of body fluids climbs above 7.45
Too little H+. Solution: Increase H+ levels in the body:
(i) Reduce excretion of CO2 via the lungs (increase blood CO2)
(ii) Increase excretion of HCO3- buffer via the kidneys
(iii) Increase generation of H+ by the kidneys
What is the difference between respiratory and metabolic acidosis?
Respiratory: - Caused by inadequate ventilation
- Can be acute or chronic
Metabolic: - Results from all conditions other
than respiratory that decrease pH
- Always chronic
Note: Only chronic states cause marked change in HCO3-
How can you gain H+?
–CO2 in blood (combines with H2O to form carbonic acid)
–Non-volatile acids from metabolism (e.g. lactic acid)
–Loss of HCO3- in diarrhoea or non-gastric GI fluids
–Loss of HCO3- in urine
Note: Loss of HCO3- is like gaining H+
What is the difference between metabolic and respiratory alkalosis?
Respiratory: - Caused by hyperventilation
- Can be acute or chronic
Metabolic: - Results from all conditions other
than respiratory that increase pH
- Always chronic
What is the treatment of metabolic alkalosis?
- Give electrolytes to replace those lost
- Give IV Cl- containing solution
- Treat the underlying disorder
How is respiratory alkalosis treated?
- Treat underlying cause
- Breathe into paper bag
(increases pCO2)
- Give IV Cl- containing solution (HCO3- excretion)
What are the actions of anti-diuretic hormone?
Interacts with V2 receptors on basolateral surface of principal cells in collecting duct of tubule
Results in increased permeability of collecting duct to H2O by insertion of aquaporin-2 (AP-2) water channels on apical surface
Maximal ADH leads to production of low amounts of concentrated urine
What causes ADH to be released?
ADH released in response to changes in plasma osmolality and effective circulating volume (ECV)
These changes are detected by osmoreceptors and baroreceptors
What is the role of osmoreceptors in dehydration?
Increased plasma osmolality stimulates osmoreceptors in the hypothalamus which trigger ADH release…
Result: more water reabsorbed from collecting ducts in kidney back into circulation. This leads to ECV
Increased osmolality also stimulates a second group of osmoreceptors in the hypothalamus which trigger thirst…
Result: promotes water intake which enters circulation. This also ECV
What are the 2 types of baroreceptors?
“Central” vascular sensors
- ‘Low pressure’ blood volume receptor (very important)
- Large systemic veins
- Cardiac atria
- Pulmonary vasculature
- ‘High pressure’ arterial stretch receptor (less important)
- Carotid sinus
- Aortic arch
- Renal afferent artery (the renal baroreceptor)
Sensors in the CNS and liver (less important)
Changes in ECV trigger 4 parallel effector pathways which act on the kidney…
(1) RAAS
(2) sympathetic nervous system
(3) ADH release
(4) ANP release
•Together, these change renal haemodynamics and Na+ transport by renal tubule cells
ECV regulation = Na+ regulation
How is the renin angiotensin aldosterone system activated?
•Principal factor controlling plasma AngII levels is renin release from the JGA
•Decreased ECV stimulates renin release via…
–Decreased renal perfusion pressure detected in the afferent arteriole - the “renal baroreceptor”
–Decreased Na+ concentration in distal tubule detected by the macula densa cells - the “renal Na+ sensor”
–Decreased systemic BP also triggers effects of the sympathetic nervous - system supplying the JGA
What are the actions of angiotensin II?
All the actions of AngII actions are designed to increase ECV:
(1) Enhances tubular Na+ transport
in the kidney - this promotes Na+ and water reabsorption from tubule
(2) Stimulation of aldosterone release from adrenal cortex so more Na+ and water is reabsorbed from distal tubule/collecting duct
(3) Acts on the hypothalamus to stimulate thirst and ADH release into circulation
…water intake adds to ECV
…ADH increases water reabsorption from the collecting duct
•Vasoconstriction of renal and other systemic vessels so systemic BP increases
What are the longer term effects of RAAS?
•AngII causes renal cell hypertrophy
…so more protein synthesis of
Na+ transporters and channels
??? Role in hypertension
Re: ACE inhibitors and ARBs
for treatment of hypertension
What are the actions of aldosterone?
All the actions of aldosterone are designed to increase ECV (in collaboration with AngII)
- Stimulates Na+ reabsorption (and K+ excretion) in the distal tubule and collecting duct
- Aldosterone also exerts indirect negative feedback on the RAAS by increasing ECV and by lowering plasma K+ concentrations
- Important in conserving Na+ and water, but also important in preventing large variation in plasma K+ levels (by causing its excretion out of the kidney)
How does ANP work?
- Atrial myocytes synthesize and store ANP.
- ECV causes atrial stretch which leads to ANP release into circulation
- ANP promotes natriuresis ( Na+ excretion from the kidney)
- Also causes renal vasodilatation so increased blood flow ® increase in GFR…so more Na+ excreted
- More Na+ reaches the macula densa so renin release by JGA is reduced – reduces the effects of AngII
- Overall effect: inhibits actions of renin and opposes effects of AngII
What does anti-natriuretic peptide do?
•In contrast, actions of ANP are all designed to lower ECV
