Kidneys
in regulation of homeostasis
Assoc. Prof. MUDr. Markéta Bébarová, Ph.D.
Department of Physiology
Faculty of Medicine, Masaryk University
This presentation includes only the
most important terms and facts. Its
content by itself is not a sufficient
source of information required to
pass the Physiology exam.
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
Compartments
Transcellular
fluid (1-2 l) –
special type
of ECF
Guyton  Hall. Textbook of Medical Physiology
60 % of the body
weight in total 5 % of the body weight
15 % of the body weight
40 % of the body weight
Body Fluids – Types and Volumes
Changes with aging
Balance between Input and Output of Fluid
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
Guyton  Hall. Textbook of Medical Physiology
osmolality 285 mosm/kg H2O


 NaCl intake, loss of water  shrinking of cells
 NaCl intake,  water input  cell edema
Body Fluids – Composition
Precise regulation of osmolality of ESF is necessary!
- osmoreceptors
- kidneys (target organ for the action of hormones below)
- antidiuretic hormone
- aldosteron
- natriuretic peptides
Humoral Regulation of Body Fluids
Antidiuretic Hormone
(vasopressin)
- effects:
water reabsorption in kidneys
(aquaporin 2)
control of blood pressure
 glycogenolysis, mediator in
the brain,  secretion of ACTH
in adenohypophysis
Guyton & Hall. Textbook of
Medical Physiology.
Humoral Regulation of Body Fluids
- regulation of secretion:
-  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)
Guyton & Hall. Textbook of
Medical Physiology.
Humoral Regulation of Body Fluids
- pathology:

 SIADH
diabetes insipidus
Antidiuretic Hormone
(vasopressin)
- the most important steroid with the mineralocorticoid effect
- mechanism of action:
binding to the mineralocorticoid receptor
 synthesis of proteins:
- namely Na+/K+-ATPase
-  number of amiloride-inhibited Na+-channels
-  activity of H+-pump
-  activity of Na+/H+-antiport
Humoral Regulation of Body Fluids
Aldosteron
 Na+ reabsorption (urine, sweat, saliva, gastric juice)
 K+ urine excretion,  acidity of urine (exchange for Na+)
 K+ content and  Na+ content in muscle and brain cells
Humoral Regulation of Body Fluids
- effects:
- the most important steroid with the mineralocorticoid effect
Aldosteron
Humoral Regulation of Body Fluids
- atrial natriuretic peptide
- other hormones od adenohypophysis (maintenance of
reactivity of zona glomerulosa)
- the most important steroid with the mineralocorticoid effect
Aldosteron
- regulation of its secretion:
- ACTH (transient effect)
- renin-angiotensine-aldosteron system
- direct stimulatory effect of  plasmatic concentration of
K+ and  Na+ (lower sensitivity)
Humoral Regulation of Body Fluids
Secondary hyperaldosteronism
- patients with the congestive heart failure, nephrosis, liver
cirhosis, renal artery constriction, hypertension, with the
salt-losing form of adrenogenital syndrome
Hyporeninemic hypoaldosteronism
Pseudohypoaldosteronism
Aldosteron - Pathology
Primary hyperaldosteronism (Conn´s syndrome)
- tumors of adrenal cortex which secretes aldosteron
- one of natriuretic peptides (BNP – cardiac ventricles, CNP – brain)
- secreted by atrial cardiomyocytes, found also in the brain
- receptors
- short half-life
Humoral Regulation of Body Fluids
Atrial Natriuretic Peptide
 natriuresis
  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
  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)
water intoxication
Humoral Regulation of Body Fluids
Water Homeostasis
Humoral Regulation of Body Fluids
Salt Homeostasis
hypocalcemia
hypercalcemia
Humoral Regulation of Body Fluids
Calcium in the Body
Ganong´s Review of Medical Physiology
Guyton & Hall. Textbook of Medical Physiology.
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
1) Secretion of H+
2) Reabsorption of HCO3
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
Regulation of H+ secretion
 activity of
Na+/H+ antiport
 activity of
H+ ATPase
RAS
tendency to 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
Diagnostics
Acid-Base Balance and its Regulation
Diagnostics
Acid-Base Balance and its Regulation
pH: 7,3
HCO3
-: 12 mEq/l
PCO2: 25 mmHg
Diagnostics - Siggaard–Andersen nomogram
Acid-Base Balance and its Regulation