Kidneys
in Regulation of Homeostasis
Assoc. Prof. MUDr. Markéta Bébarová, Ph.D.
Department of Physiology
Faculty of Medicine, Masaryk University
A42. Kidney in regulation of homeostasis
A3. Compartmentalization of body fluids
A4. Differences between intra- and extracellular fluids
B70. Regulation of body fluid volume
B71. Regulation of constant osmotic pressure
B53. Formation and secretion of posterior pituitary hormones
B58. Adrenal cortex. Functions, malfunctions.
B62. Natriuretic peptides
B61. Bone formation and resorption. Regulation of calcaemia.
A30. Homeostasis (acid-base balance)
Homeostasis
Maintainance of Constant Volume and Composition of Body
Fluids
Maintainance of Acid-Base Balance
= maintainance of stable conditions in the internal body
environment
Constant Volume and
Composition of Body Fluids
- Regulation by Kidneys -
Body Fluids – Types and Volumes
Guyton  Hall. Textbook of Medical Physiology
Body fluids
occupy 60%
of the body
weight.
Body Fluids – Types and Volumes
Body Fluids – Types and Volumes
Guyton  Hall. Textbook of Medical Physiology
5% of the
body weight
15% of the
body weight
40% of the
body weight
Body fluids
occupy 60%
of the body
weight.
Transcellular
fluid (1-2 l) –
special type
of ECF.
(peritoneal,
pericardial,
synovial,
cerebrospinal
and intraocular
fluid)
Balance between Input and Output of Fluid
Guyton  Hall. Textbook of Medical Physiology
Body Fluids – Types and Volumes
Guyton  Hall. Textbook of Medical Physiology
ECF vs. ICF
Body Fluids – Composition
Guyton  Hall. Textbook of Medical Physiology
plasma vs. ISF
Body Fluids – Composition
osmolality 285 mosm/kg H2O


 NaCl intake, loss of water  water leaves cells
(shrinking of cells)
 NaCl intake,  water input  water sucked into cells
by osmosis (cell edema)
Body Fluids – Composition
Guyton & Hall. Textbook
of Medical Physiology.
Precise regulation of osmolality of ESF is necessary!
- osmoreceptors
Body Fluids – Composition
- kidneys (target organ for the action of hormones below)
- antidiuretic hormone
osmolality 285 mosm/kg H2O


 NaCl intake, loss of water  water leaves cells
(shrinking of cells)
 NaCl intake,  water input  water sucked into cells
by osmosis (cell edema)
- aldosteron
- natriuretic peptides
Humoral Regulation of Body Fluids
Antidiuretic Hormone
(vasopressin)
- effects:
water reabsorption in kidneys
(collecting duct, aquaporin 2)
Guyton & Hall. Textbook of
Medical Physiology.
control of blood pressure (water
reabsorption, vasoconstriction)
 glycogenolysis, mediator in
the brain,  secretion of ACTH
in adenohypophysis
Humoral Regulation of Body Fluids
- regulation of secretion:
Guyton & Hall. Textbook of
Medical Physiology.
-  osmolality
-  volume of ECF
 -  osmolality,  volume of ECF

- pain, emotions, stress (surgical),
physical exertion; standing
- nausea, vomitting
- angiotensine II
- morphin, nicotine, barbiturates, …
- alcohol; antagonists of opioids
Antidiuretic Hormone
(vasopressin)
- the most important steroid with the mineralocorticoid effect
- mechanism of action:
binding to the mineralocorticoid receptor  binding of the
hormone-receptor complex to DNA  mRNA  synthesis
of proteins:
- namely Na+/K+-ATPase
-  number of amiloride-inhibited Na+-channels in the
membrane of target cells
-  activity of H+-pump in collecting ducts of the renal cortex
-  activity of Na+/H+-antiport in both distal and proximal parts
of nephrons
Start of the effect even 10 – 30 min after
release of the hormone!
Humoral Regulation of Body Fluids
Aldosteron
 Na+ reabsorption from urine, sweat, saliva, gastric juice
 K+ urine excretion,  acidity of urine (exchange for Na+)
 K+ content and  Na+ content in muscle and brain cells
- ACTH from the adenohypophysis (a transient effect)
- renin-angiotensine-aldosteron system
- direct stimulatory effect of  plasmatic concentration of
K+ (even a small change – even after a meal rich for K+
- fruit, vegetable) and  Na+ (only a big change)
Humoral Regulation of Body Fluids
- effects:
- regulation of its secretion:
- the most important steroid with the mineralocorticoid effect
Aldosteron
Ganong´s Review of Medical Physiology
Humoral Regulation of Body Fluids
Renin-Angiotensine-Aldosteron System
Humoral Regulation of Body Fluids
- atrial natriuretic peptide (inhibition of renin secretion, 
reactivity of zona glomerulosa to angiotensine II)
- other hormones od adenohypophysis (besides ACTH;
maintenance of reactivity of zona glomerulosa)
- the most important steroid with the mineralocorticoid effect
Aldosteron
- ACTH from the adenohypophysis (a transient effect)
- renin-angiotensine-aldosteron system
- direct stimulatory effect of  plasmatic concentration of
K+ (even a small change – even after a meal rich for K+
- fruit, vegetable) and  Na+ (only a big change)
- regulation of its secretion:
- one of natriuretic peptides (BNP – cardiac ventricles, CNP – brain)
- secreted by atrial cardiomyocytes, found also in the brain
- receptors (ANPR-A – the highest affinity to ANP, ANPR-B – CNP, ANPR-C – all NP)
- short half-life
Humoral Regulation of Body Fluids
Atrial Natriuretic Peptide
 natriuresis (1.  GFR – increased area for the filtration through
relaxation of mesangial cells, 2.  Na+ excretion – decrease
tubular Na+ reabsorption)
  reactivity of vascular smooth muscles for vasocontrictive
substances
 inhibition of renin secretion,  reactivity of zona glomerulosa for
stimuli  aldosteron secretion
 inhibition of ADH secretion   water excretion
 -  CVP at orthostasis
 -  ECF volume (atrial cells´ stretch at higher atrial filling)
  BP (also through the brain stem)
Humoral Regulation of Body Fluids
- effects (through ↑ cGMP):
- regulation of its secretion:
Atrial Natriuretic Peptide
- one of natriuretic peptides (BNP – cardiac ventricles, CNP – brain)
Ganong´s Review of Medical Physiology
Guyton & Hall. Textbook of Medical Physiology.
hypocalcemia
hypercalcemia
Humoral Regulation of Body Fluids
Calcium in the Body
Humoral Regulation of Body Fluids
Parathormone
Vitamin D
Calcitonin
Hormonal Regulation of Calcemia
Humoral Regulation of Body Fluids
Hormonal Regulation of Calcemia
Acid-Base Balance
- Regulation by Kidneys -
1) Buffers
2) Lungs
3) Kidneys
Acid-base balance is regulated by:
 fast regulation (seconds)
 fast regulation (minutes even hours)
 slower regulation (hours even days) but the most powerful
 elimination of acids and bases from the body
 elimination of CO2 from the body (H2CO3  H2O + CO2)
 pH changes attenuated by binding and release of H+:
buffer + H+ H - buffer
[H+]
[H+]
direction to the right favoured till free buffer is available
direction to the left favoured, H+ released
Acid-Base Balance and its Regulation
Regulation of Acid-Base Balance by Kidneys
 by excretion of acid or alkalic urine
 a high amount of HCO3
- still filtered in the glomerulus
 a high amount of H+ still secreted in renal tubules
about 80 mEq of non-volatile acids are formed in the course of
metabolic processes per day – have to be excreted by kidneys
GFR 180 l/day, [HCO3
- ]plasma 24 mEq/l  4320 mEq HCO3
filtered
per day – almost all ordinarily reabsorbed
 filtered HCO3
- / secreted H+
Acid-Base Balance and its Regulation
Regulation of Acid-Base Balance by Kidneys
 in the proximal tubule, thick loop
of Henle and at the beginning of
the distal tubule
Na+/H+-antiport
>90% HCO3
- reabsorbed – only a slight
acidification of the urine!
Reabsorption of HCO3
- across the
basolateral membrane facilitated
by:
 Na+-HCO3
- co-transport
 Cl--HCO3
- exchanger
(the proximal tubule)
(the end of proximal tubule and
the following parts of tubulus
except for the thin loop of
Henle)
Acid-Base Balance and its Regulation
1) Secretion of H+
2) Reabsorption of HCO3
-
Regulation of Acid-Base Balance by Kidneys
 in the final part of distal tubule
and in the collecting duct
primary active transport of H+
(intercalated cells)
acidification of urine
Acid-Base Balance and its Regulation
1) Secretion of H+
2) Reabsorption of HCO3

in the proximal tubule, thick loop
of Henle and at the beginning of
the distal tubule
Na+/H+-antiport
>90% HCO3
- reabsorbed – only a slight
acidification of the urine!
3) Production of HCO3
- de novo
 Phosphate buffer (HPO4
2-, H2PO4
-)
HPO4
2- and H2PO4
- are reabsorbed less
than water  their concentration in the
tubular fluid gradually rises
 Ammonium buffer (NH3, NH4
+)
NH4
+ originates from glutamine – the
proximal tubule, thick ascending loop of
Henle and distal tubule
Regulation of Acid-Base Balance by Kidneys
Acid-Base Balance and its Regulation
1) Secretion of H+
2) Reabsorption of HCO3
-
 Ammonium buffer (NH3, NH4
+)
the collecting duct (permeable for NH3
but far less for NH4
+ - excreted by urine)
50% of H+ secretion and HCO3
- formed de
novo!
Regulation of Acid-Base Balance by Kidneys
3) Produkce nového HCO3
Acid-Base
Balance and its Regulation
1) Secretion of H+
2) Reabsorption of HCO3

Phosphate buffer (HPO4
2-, H2PO4
-)
HPO4
2- and H2PO4
- are reabsorbed less
than water  their concentration in the
tubular fluid gradually rises
Regulation of Acid-Base Balance by Kidneys
Regulation of H+ secretion
 -  pCO2 in ECF (respiratory acidosis; direct stimulation due
to  formation of H+ in tubular cells)
-  pH in ECF (respiratory or metabolic acidosis)
-  secretion of aldosteron (stimulates H+ secretion in
intercalated cells of collecting ducts; Conn´s syndrome -
alkalosis)
Acid-Base Balance and its Regulation
Regulation of Acid-Base Balance by Kidneys
Acidosis – correction by kidneys
renal correction :  HCO3
- in ECF   filtered HCO3
- 
complete reabsorption of HCO3
- + its formation de novo
(HCO3
- not excreted) +  H+ excretion  pH normalization
 metabolic acidosis: due to  HCO3


 respiratory acidosis: due to  PCO2 (hypoventilation)
renal correction:  PCO2 in ECF   PCO2 in tubular cells 
 formation of H+ and HCO3
- in tubular cells   H+
secretion +  HCO3
- reabsorption  pH normalization
Acid-Base Balance and its Regulation
pH = 6.1 + log
HCO3
-
0.03 x PCO2
Regulation of Acid-Base Balance by Kidneys
Alkalosis – correction by kidneys
 
renal correction:  HCO3
- in ECF   filtered HCO3
- 
incomplete HCO3
- reabsorption (lack of H+)   HCO3
excretion
by urine  pH normalization
 metabolic alkalosis: due to  HCO3

respiratory alkalosis : due to  PCO2 (hyperventilation)
renal correction:  PCO2 in ECF   PCO2 in tubular cells
  formation of H+ and HCO3
- in tubular cells   H+
secretion +  HCO3
- reabsorption  pH normalization
Acid-Base Balance and its Regulation
pH = 6.1 + log
HCO3
-
0.03 x PCO2