Download Homeostasis

Homeostasis
Árpád Dobolyi
Laboratory of Molecular and Systems Neurobiology,
Department of Physiology and Neurobiology, Eötvös
Loránd University
Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
The internal environment and its evolutionary origin
• Intracellular space was formed by the appearance of cellular organisms
(about 3 billion years ago). Its composition differed from that of the ancient
ocean.
• External environment was the sea whose composition was relatively stable.
Each cell was in interaction with the sea, took up and released substances.
• With the appearance of multicellular organisms, most of the cells are not in
contact with the ocean, but rather the interstitial fluid. This is their internal
environment (Claude Bernard: „milieu intérieur”, ~1840), whose composition
resembles to that of the ancient ocean.
• Subsequently, a circulatory system containing blood developed whose
function is to connect the internal environment of different cells of the organism
with each other and the external environment
Transfer of substances in multicellular organisms
Extracellular fluid
•
•
Body cells are situated in
watery internal environment
through which life-sustaining
exchanges are made
Extracellular fluid (ECF):
Fluid environment in which
the cells live (fluid outside the
cells)
– Two components:
• Plasma
• Interstitial fluid
•
Intracellular fluid (ICF) - Fluid
contained within all body cells
Homeostasis
• Defined as maintenance of a relatively
stable internal environment (Walter
Bradford Cannon, 1932, The Wisdom of
the Body).
- Homeostasis is essential for
survival and function of all
cells
- Does not mean that
composition, temperature, and
other characteristics are
absolutely unchanging
• Interstitial fluid is in interaction with the
blood. Thus, the organisms provide
homeostasis through the regulation of
the composition of the blood.
Blood composition
 Suspension of cells in plasma (carrier fluid)
45% Cells
55% Plasma
Formed elements (e.g. cells)
Red cells (erythrocytes)
5x106/mL
White cells (leukocytes)
7x103/mL
Platelets (thrombocytes)
3x105/mL
99%
< 1%
Blood composition
Blood Plasma
• Straw colored clear liquid
• Contains 90% water
• 7% plasma proteins
 created in liver
 confined to bloodstream
 albumin
 maintain blood osmotic pressure
 immunoglobulins
 antibodies bind to foreign
substances called antigens
 form antigen-antibody complexes
 fibrinogen
 for clotting
• 2% other substances
 Nutrients, electrolytes, gases, hormones, waste products
Formed Elements of Blood
• Red blood cells (R.B.C.)
• White blood cells (W.B.C.)
 granular leukocytes
 neutrophils
 eosinophils
 basophils
 agranular leukocytes
 lymphocytes - T cells, B cells, natural killer cells
(N.K.C)
 monocytes
• Platelets (special cell fragments)
Functions of red blood cells
1. Transport oxygen from lungs to the tissues
(oxyhemoglobin).
2. Transport carbon-di-oxide from tissues to lungs
(carboxyhemoglobin)
3. Hemoglobin acts as a buffer and regulates the
hydrogen ion concentration (acid base balance)
4. Carry the blood group antigens and Rh factor
Ion concentrations within and outside a
typical mammalian cell
Some components of homeostasis
Isoionia: homeostasis of ion concentrations and organic small molecules
Ion concentrations in the blood plasma:
Na+.......143 mmol/l
Cl-..........................103 mmol/l
K+.............4 mmol/l
HCO3-.. ..................24 mmol/l
Ca++......2,5 mmol/l
H2PO4- és HPO4--…1 mmol/l
Mg++.........1 mmol/l
Some organic small compounds:
Glocose….4.5-5.50 mmol/l
Urea........2.5-6.3 mmol/l
Isosmosis: Osmotic pressure of blood plasma: 290 milliosmol/l
Isohidria: H-ion concentration: [H+]=35-40 nmol/l (pH: 7.38-7.42)
Buffer systems: carbonates, phosphates, hemoglobin, plasma proteins
Physical parameters: isovolume, isotermia
Causes of deviation from homeostasis
• Homeostasis is continually being disrupted by
– External stimuli
• heat, cold, lack of oxygen, pathogens, toxins
– Internal stimuli
• Body temperature
• Blood pressure
• Concentration of water, glucose, salts, oxygen, etc.
• Physical and psychological distresses
• Disruptions can be mild to severe
• If homeostasis is not maintained, death may
result
Homeostatic control systems
In order to maintain homeostasis, control
system must be able to
– Detect deviations from normal in the internal
environment that need to be held within narrow
limits
– Integrate this information with other relevant
information
– Respond: make appropriate adjustments in order
to restore factor to its desired value (set point)
Temperature regulation by thermostat
Temporal change of temperature as a
result of regulation by thermostat
Classification of homeostatic control systems
Based on location:
- Intrinsic controls:
• Local controls that are inherent in an organ
- Extrinsic controls
• Regulatory mechanisms initiated outside an organ
• Accomplished by endocrine and nervous systems
Based on mechanism:
- Feedforward - term used for responses made in anticipation of a
change
- Feedback - refers to responses made after change has been
detected
• Negative: original stimulus reversed
• Positive: original stimulus intensified
Feedback Loop
•
Receptor - structures that monitor a controlled condition and detect
changes
•
Control center - determines next action
•
Effector
– receives directions from the control center
– produces a response that restores the controlled parameter
Example of negative feedback loop to
control blood glucose concentration
•
Blood glucose
concentrations rise after
a sugary meal (the
stimulus), the hormone
insulin is released and it
speeds up the transport
of glucose out of the
blood and into selected
tissues (the response),
so blood glucose
concentrations decrease
(thus decreasing the
original stimulus).
Homeostasis of
blood pressure
• Baroreceptors in walls of
blood vessels detect an
increase in blood pressure
• Brain receives input and
signals blood vessels and
heart
• Blood vessels dilate, heart
rate decreases
• Blood pressure decreases
Positive feedback during childbirth
• Stretch receptors in walls of uterus send signals
to the brain
• Brain induces release of hormone (oxytocin) into
bloodstream
• Uterine smooth muscle contracts more forcefully
• More stretch, more hormone, more contraction
etc.
• Cycle ends with birth of the baby & decrease in
stretch
Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
Hormones – organic biologically active compounds
of different chemical nature that are produced
by the endocrine glands, enter directly into blood
and accomplish humoral regulation of the
metabolism of compounds and functions on the
organism level.
Hormonoids (tissue hormones) – compounds that
are produced not in glands but in different
tissues and regulate metabolic processes on the
local level, but some of them (serotonin,
acetylcholine) enters blood and regulate
processes on the organism level.
Four methods of cell-to-cell communication ranging
from direct to remote communication
Endocrine system
• Endocrine system is composed of a number of glands,
which are specialized tissues that produce hormones
• Features of the endocrine system:
1.
2.
3.
4.
Endocrine glands have a rich supply of blood
Hormones, produced by the endocrine glands are
secreted into the bloodstream
Hormones travel in the blood to target cells close by or
far away from point of secretion
Hormone receptors are specific binding sites on the
target cell
Endocrine glands
1. Hypothalamus
2. Pituitary
3. Epiphysis (pineal
gland)
4. Thyroid (and
parathyroid gland)
5. Thymus
6. Adrenal gland
7. Langergans’ islands
of pancreas
8. Sex glands
(ovary or testis)
Chemical nature of hormones
Examples of
different types of
chemical signals
used for cell-to-cell
communication
Secretion of hormones into the blood
• Peptide and protein hormones are
secreted by exocytosis
• Steroid (lipophilic) hormones
continuously penetrate the membrane
-they are not accumulated in cells
-their concentration in blood is
determined by the speed of
synthesis)
Protein and peptide hormones are synthesized into
the endoplasmic reticulum
Figure 15-14 Essential Cell Biology (© Garland Science 2010)
Functions of different parts of the Golgi apparatus
Constitutive and regulated exocytosis
The mechanism of exocytosis of protein and peptide hormones
Electromicroscopic image of insulin sscretion
Posttranslational modification of peptide hormones
Examples of the position of peptide hormones in the
newly synthesized protein chains
Cleavage of prohormones by endopeptidases
(prohormon convertases) in the Golgi apparatus
Transport of hormones in blood
• Proteins and peptides – in free state
• Steroid hormones and hormones of thyroid gland – bound
with alpha-globulins or albumins
• Catecholamines – in free state or bound with albumins,
sulphates or glucuronic acid
• Reach the target organs
• Cells have the specific receptors to certain hormone
Hormones act where they have receptors
Target cells
Target cells refer to cells that contain specific receptors
(binding sites) for a particular hormone. Once a hormone
binds to receptors on a target cell, a series of cellular
events unfold that eventually impact gene expression and
protein synthesis.
Action of steroid hormones
• Steroid hormones enter through the cell
membrane and bind to receptors inside of the
target cell
• These hormones may directly stimulate
transcription of genes to make certain proteins
• Because steroids work by triggering gene activity,
the response is slower than peptide hormones
Receptors of steroid hormones
steroid hormone
(extracellular
fluid)
2 The hormone binds to a
receptor in the nucleus or to
a receptor in the cytoplasm
that carries it into the nucleus
3 The hormone–receptor
complex binds to DNA and
causes RNA polymerase to
bind to a nearby promoter
site for a specific gene
1 A steroid hormone
diffuses through the
plasma membrane
plasma
membrane
DNA
hormone receptor
ribosome
RNA polymerase
5 The mRNA leaves the
nucleus, then attaches to a
ribosome and directs the
synthesis of a specific protein
product
mRNA
4 RNA polymerase catalyzes
the transcription of DNA into
messenger RNA (mRNA)
gene
new protein
nuclear
envelope
(cytoplasm)
(nucleus)
Action of protein/peptide
hormones
• Protein/peptide hormones do not enter the
cell directly. These hormones bind to
receptor proteins in the cell membrane.
• When the hormone binds with the receptor
protein, a secondary messenger molecule
initiates the cell response
• Protein/peptide hormones often produce
fast responses
Receptors of peptide hormones
peptide or amino
acid-derived
hormone
(first messenger)
1 The hormone binds to
a receptor on the plasma
membrane of a target cell
(extracellular
fluid)
receptor
2 Hormone–receptor binding
activates an enzyme that catalyzes
the synthesis of a second messenger,
such as cyclic AMP
cyclic AMPsynthesizing
(cytoplasm)
enzyme
ATP
active
enzyme
product
cyclic AMP
(second messenger)
4 The activated enzymes
catalyze specific reactions
plasma membrane
inactive
enzyme
reactant
3 The second
messenger activates
other enzymes
nuclear
envelope
(nucleus)
Types of membrane-bound receptors
Inactivation of hormones
•
•
Hormones are eventually broken down
(metabolized) and/or excreted from the body
The rate of removal from the circulation is fairly
constant for a given hormone
The length of time it takes to remove half of the
amount of hormone from the circulation is the
half-life of that hormone.
100%
Amount of Hormone
•
50%
0%
Time
Inactivation of hormones 2
Hormones are inactivated mainly in liver
Inactive metabolites are excreted mainly with urine
Half-time life
- from several min to 20 min – for the majority of
hormones
- till 1 h – for steroid hormones
- till 1 week – for thyroid hormones
Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
Some components of homeostasis
Isoionia: homeostasis of ion concentrations and organic small molecules
Ion concentrations in the blood plasma:
Na+.......143 mmol/l
Cl-..........................103 mmol/l
K+.............4 mmol/l
HCO3-.. ..................24 mmol/l
Ca++......2,5 mmol/l
H2PO4- és HPO4--…1 mmol/l
Mg++.........1 mmol/l
Some organic small compounds:
Glocose….4.5-5.50 mmol/l
Urea........2.5-6.3 mmol/l
Isosmosis: Osmotic pressure of blood plasma: 290 milliosmol/l
Isohidria: H-ion concentration: [H+]=35-40 nmol/l (pH: 7.38-7.42)
Buffer systems: carbonates, phosphates, hemoglobin, plasma proteins
Physical parameters: isovolume, isotermia
Potassium homeostasis
• Blood plasma concentration: 3.6-5.0 mmol/l
• Excretion: 90% kidney, 10% gut
• Causes of low potassium ion level:
- reduced oral intake
- intestinal loss: diarrhea, vomiting
- renal loss: kidney disease
Consequence:
Ki/Ke  muscles cannot properly contract
• Causes of high potassium ion level :
- increased potassium intake (combined with kodney disease)
- reduced excretion in kidney (e.g. due to digitalis poisining)
- potassium loss from cells (trauma, hemolysis, cytostatics)
Consequence: :
Elevated excitability of muscles: spasms of sceletal muscles, and cardiac
problems
Passive regulation of blood plasma
potassium from „internal store”
Passive control: extracellular K-ion level acts on the activity of Na-K pump and
potassium channels present in the plasmamembrane of all cells. Small relative
change of the intracellular potassium level, which has no effect on intracellular
processes, can significantly compensate the smaller level of potassium in the
extracellular space
Compartments interacting with the blood:
potential surfaces of regulations
• Gastrointestinal tract
- Behaviors determining feeding and drinking
- Regulation of absorption
- Secretion with faces
• Kidney
• Lung (mostly for gases)
• Sweat
• Internal stores
- Binding proteins in the blood
- Intracellular space of the cells
- Organs specialized for storage
Nephron
Reabsorption in the proximal convoluted tubule
Nephron
Reabsorption in the distal convoluted tubule and
the collecting duct
Hormonally regulated active control of blood
potassium ion level
- 92% of potassium ion of the primary urine is
reabsorbed before the collecting duct
- There is a low speed non-controlled potassium ion
reabsorption in the medully, which reabsorbes all
potassium ion leading to zero excretion without
regulation
- Active regulation: aldosterone, a
mineralocorticoid steroid hormone released from the
adrenal gland leads to increased secretion of
potassium in the initial segment of the collecting
duct thereby reducing blood plasma potassium ion
level. This is the only active regulation of potassium
level of the blood.
- Regulation has only one direction, and is not very
strong but still sufficient as passive regulation helps
out and potassium intake with food is relatively
constant in the long term. Potassium does not even
have a specific taste as sodium ion determines
primarily the salty taste.
Mechanism of action of aldosterone
Aldosterone
increases the
activity of the
Na-K pump
thereby
increasing
intracellular
potassium ion
level, which
leads to its
secretion to
the lumen of
the collecting
tube.
Endocrine glands
1. Hypothalamus
2. Pituitary
3. Epiphysis (pineal
gland)
4. Thyroid (and
parathyroid gland)
5. Thymus
6. Adrenal gland
7. Langergans’ islands
of pancreas
8. Sex glands
(ovary or testis)
Adrenal gland
Mineralocorticoids
Glucocorticoids
Sexual steroids
Catecholamines
Synthesis and regulation of aldosterone secretion
Outline of the lecture
1. Internal environment of living organisms,
homeostasis
2. Homeostatic regulations – endocrine system,
hormones
3. Examples of homeostatic regulations not
requiring the nervous system
– Potassium level of blood plasma
– Calcium level of blood plasma
4. Homeostatic regulations – nervous system
– Elements of the nervous system
– Hypothalamus
5. Examples of regulations involving the brain
– Water balance
Calcium content of human
Total body calcium = 1500 g
Bone 99%
Intracellular Ca
0.9%
Interstitial Ca
0.075%
Plasma Ca
0.025%
Plasma Ca:
Bound to proteins– 45%
In complexes– 10%
Ionized free Ca – 45%
Biologically active
fraction
Calcium homeostasis
Daily Ca intake
1000 mg
200 mg
400 mg
Extracellular
calcium (1500 mg)
200 mg
200 mg
10.000 mg
9.800 mg
800 mg
200 mg
Endocrine glands
1. Hypothalamus
2. Pituitary
3. Epiphysis (pineal
gland)
4. Thyroid (and
parathyroid gland)
5. Thymus
6. Adrenal gland
7. Langergans’ islands
of pancreas
8. Sex glands
(ovary or testis)
Regulatory hormones of calcium homeostasis
The major regulatory hormone is parathyroid hormone (PTH), which
increases calcium ion level in the plasma. PTH is produced in the
parathyroid gland when blood calcium ion levels decrease.
Another hormone, calcitonin has the opposite effects, it increases plasma
calcium ion level. Calcitonin is produced in C cells of the thyroid
hormone.
Calcium receptor
senses calcium ion
level in the plasma
Intracellular signaling
of calcium receptor
PTH secretion is inhibited
Calcitonon secretion is stimulated
Target tissues of hormones regulating
plasma calcium ion level
Parathyroid hormone:
•
•
•
kidney
– Stimulates calcium ion reabsorption
– Stimulates the synthesis of vitamin D
bone
– Stimulates osteolysis
Gastrointestinal system
– No direct effect
– Vitamin D increases the absorption of calcium iom
in the small intestine
Calcitonin:
•
bone
– Inactivates osteoclasts thereby inhibits osteolysis
Regulation of calcium homeostasis
Daily Ca intake
1000 mg
Calcitonin
200 mg
400 mg
extracellular
calcium (1500mg)
200 mg
200 mg
10.000 mg
800 mg
9.800 mg
PTH
Vitamin D
200 mg
Comparison of the regulation of plasma
calcium to that of potassium ion
• Parathyroid hormone increases calium ion level while
aldosterone descreases potassium ion level, so the major
direction of regulation is the opposite
• Calcium ion level can be regulated in both direction as not only
parathyroid hormone but also calcitonin plays a role, which has
opposite effect on plasma calcium level
• Parathyroid hormone acts to increase calcium ion levels in 3
different tissues while aldosterone regulates potassium ion level
only in the kidney
• Parathyroid hormone has indirect effects, too. It includes another
hormone, vitamin D in the control of plasma Ca ion level
• Both regulation is coupled (potassium to sodium, calcium to
phosphate), both opposing directions
• Neither regulations involves the nervous system