HOMEOSTASIS

HOMEOSTASIS AND FLUID COMPARTMENTS:

● Body components:
○ Differentiated cells: specialized function.
○ Tissues: groups of cells with related function - muscle, nervous, connective
and epithelium.
○ Organ: functional unit.
○ Organ system: several organs act together to perform specific functions. They
provide a means for exchange of materials between the external environment
surrounding the body and its interior.
● Fluid compartments:
○ ICF: intracellular fluid compartments (cytoplasm): high concentration of
potassium.
○ ECF: extracellular fluid compartments, surrounds the cells: high concentration
of sodium.
■ IVF: intravascular fluid compartment
■ IS: interstitial fluid compartment: spaces between body components
that are usually filled with connective tissue.
○ Disequilibrium between ECF and ICF:
■ Regulated by ATPase enzyme that organizes the distribution of
potassium and sodium, making sure that the concentration is different.
○ Total body water: 60%
■ ICF = cytoplasm = ⅔ of total body water.
■ ECF = surrounds cells, is an interface with external environment = ⅓
of total body water.
● IVF = fluid phase of blood = plasma = 3/12 TBW
● IS = 1/12 TBW

● Self-regulating mechanisms:
○ Most of the systems work through negative feedback.
○ Equilibrium: equal amount of substance, will occur if there is sufficient time for
exchange and if there is no barrier to movement from one compartment to the
other. (IVF = IS)
 ■ No net transfer of substances or energy.
■ No barrier to movement.
■ No energy expenditure to maintain.
○ Steady state: constant amount or concentration of substance in
compartments. (ICF = ECF)
■ Input = output
■ Requires energy to maintain.
● What is homeostasis?
○ Maintenance of extracellular fluid constituents as relatively constant.
○ Maintenance of the ECF as a steady state.
○ Central theme of physiology.
● Homeostasis and illness:
○ Input = output → wellness.
○ Input ≠ output → illness or pathophysiology.
● Homeostatic control and reflex loops:

REGULATION OF HOMEOSTASIS:
● Homeostatic control:
○ Reflex control: response made at a distance from target cell, is composed by
an input stimulus, an integrator of the stimulus and a response (effector).
■ Endocrine: chemical that's released on the blood so that it can reach
the target cell.
■ Neuron: synapse, small space between neuron and the target cell
where the chemical is released.
○ Local response: occurs at target cell, with neighboring cells, mediated by
proteins called cytokines.
■ Paracrine: one cell controls the action of its neighboring cell through
chemicals that it releases.
■ Autocrine: the chemicals released by a cell are absorbed by the same
cell so it is auto regulated.
■ Gap junction: two cells physically connected by a bridge that allows
them to exchange ions.
● Reflex components:
○ 1- Stimulus.
○ 2- Sensor: afferent path, goes inward, inside the body.
○ 3- Integration center: brain, set point.
○ 4- Effectors: response, efferent path, goes outward.
○ 5- Stimulus: the body acts upon the stimulus.
● Mass balance: in the body refers to a steady state in which the total amount of a
substance equals its intake plus its production minus its output.
● Mass flow: mass balance over time:
○ Mass flow (amount/min) = (concentration (amt/vol)) x (volume flow (vol/min))
● Negative feedback reflex loops: the response removes the stimulus. It allows the
system to resist deviation of a given parameter from a preset range (or set point).
○ Simple: involves two cellular compartments, stimulus is received by an
endocrine cell for example that will create a chemical that will act on the
stimulus to eliminate it.
○ Complicated: involves more than two cellular compartments, the stimulus acts
on a cell, that acts on another cell, that acts on another and so on. Each cell
will then have a negative feedback. The feedback signal inhibits secretion at
all previous levels.
● Positive feedback reflex loops: reinforces the stimulus rather than decreasing or
removing it, therefore it is an unstable condition. The consequence of this is not to
maintain homeostasis, but to elicit a change. Unlike the negative, this type of
feedback is a finite loop, often reduced or terminated by the negative.
● Feed-forward control: enabled the body to anticipate a change and start a reflex loop.
An example is when the smell of food makes our mouths water, given that the saliva
lubricates the food during chewing.
● Tonic control: unlike negative and positive feedback where we turned something off
or on. It is the modulation (up and down) of a specific activity of a specific cell.

● Antagonistic control: mediated by nervous systems that do opposite things.

Parasympathetic and sympathetic systems.

● Circadian rhythms: biological systems in the body that change every 24 hours
automatically, without any input. Different people have different circadian rhythms.
 ● General concepts:
○ Stability of internal variables is achieved by balancing inputs and outputs to
the body and among organ systems.
○ In negative feedback systems, a change in a variable is corrected by bringing
the body back to the initial set point. However, set points can be reset.
○ Not always possible to maintain everything relatively constant. There is a
hierarchy of importance in the maintenance of life.
● End of video question:
○ Why are so many of the homeostatic control mechanisms in the body so
complex?
■ Faster response.
■ Different types of effectors used.
■ Back-up system if another effector fails.
● Problem: Identify the components of the reflex loop in the following scenario. You
have finished the marathon in just under three hours. You are tired, sweating
profusely, and start to drink Gatorade. After a few minutes you are still tired but no
longer sweating or thirsty.
○ Answer: Sweating = loss of ECF water (stimulus); the stimulus is recognized
by the hypothalamus (integrator); the thirst response (effector) is triggered;
the individual drinks Gatorade; this removes the stimulus; i.e., no longer
thirsty; this is classic negative feedback
TRANSPORTERS, PUMPS AND CHANNELS:
● Basis of physiologic processes:
○ Growth.
○ Metabolic activities.
○ Sensory perception.
● Basis of disease:
○ Defective transporters (cystic fibrosis).
○ Defective channels (long QT syndrome, paralysis).
● Basis of pharmacological therapies:
○ Hypertension (diuretics).
 ○ Stomach ulcers (proton pump inhibitors).
● Simple diffusion and gap junctions: easiest ways of moving materials across cell
membranes.
○ Flux: random movement of molecules across a surface per unit time.
○ Net flux is determined by gradients.
■ From high concentration to low concentration.
○ Gap junctions (nexus) permits diffusion of ions between coupled cells.
● Characteristics of simple diffusion:
○ Moves from high to low concentration.
○ Requires no energy expenditure.
○ Continues until equilibrium is reached.
○ Occurs rapidly over short distances and slowly over long distances.
○ Is directly related to temperature (faster at higher temperatures).
○ Is inversely related to the size of the molecule (larger molecules move
slower).
○ Is dependent on the total surface area and thickness of the membrane barrier.
● Facilitated diffusion: material is transported with the help of transporters (proteins),
does not require ATP for activity.
○ Each solute has a specific transporter.
○ Transporters in a membrane are limited, so at a certain point, they will be
saturated and the net flux across the membrane becomes constant.
○ Some transporters can move more than one solute at any time.
■ Symporter: solutes are being moved in the same direction.
■ Antiporter: solutes are being moved in opposite directions.

● Channels: pore across membrane, some are open (solutes move by diffusion from
high to low concentration) and some can close (are gated) and the opening is
regulated.
○ Ligand (chemical) gating: requires binding of specific chemical to open.
○ Voltage gating: requires a specific gradient of electrical charge across the
membrane to open (cells contain negatively charged proteins, the ECF is
more positive than the ICF).
○ Mechanical gating: requires specific tension to open.
● Pumps mediate active transport.
○ Moves solute from low concentration to high concentration, always using ATP.
○ Enzymes called ATPases.
● General concepts:
○ Movement of a solute across the lipid bilayer (cell membrane) is dependent
on its size, charge and solubility.
 ○Net flux of a solute is determined by gradients.
○A permeable solute crosses the membrane by simple diffusion (slow), moving
down its concentration gradient until equilibrium is reached.
○ A non-permeable solute crosses the membrane by facilitated diffusion (fast)
using transporters. This process requires a gradient, is saturable and is
specific.
○ Primary active transport moves a solute against its concentration gradient.
This mechanism requires energy, exhibits specificity and is saturable (there is
a finite number of pumps).
○ Secondary active transport couples the activity of a co-transporter with a
pump. This is used for transcellular transport of a solute.
● End of video questions:
○ Hydrophobic molecules such as fatty acids enter the cells by:
■ Simple diffusion.
○ The PepT is a H+/peptide antiporter located in the small intestine. It has the
following characteristics:
■ Exhibits maximal transport when saturated.
■ Requires H+ and peptides for activity.
SOLUTE AND WATER TRANSPORT:
● Concentration of water:
○ Is higher when there is no solute. When a solute is added to water, its
concentration decreases.
● Osmosis:
○ When the membrane between two compartments is permeable to solute both
compartments are going to keep their size and the concentration of both
water and solute will be at equilibrium.
○ When the membrane between two compartments is impermeable to the
solute only the water will move between them, causing the compartment that
has more solute and smaller water concentration to grow in size. This
happens so that the concentration can be the same in both compartments.
● Osmosis is the movement of water.
○ It occurs only by diffusion.
○ Water moves from compartments with dilute solutions to concentrated
solutions to make the concentrations of water and solute equal.
○ Uses aquaporin channels = facilitated diffusion.
○ Pure water = higher concentration.
● Important terms:
○ Molarity: number of mole / volume (where 1 mole = 6 x 10^23 molecules)
○ Osmolarity: (number molecule / volume) x (number particles / molecule)
○ Osmolality: (number molecule / Kg water) x (number particles / molecule)
○ We will consider osmolarity and osmolality to be the same thing.
○ In body, osmolarity and osmolality = 300 mOsM
● Isosmotic solutions: both compartments have the same number of solute particles.
● Hyperosmotic solutions: when solution A has more solute particles (mOsM) than B,
solution A is hyperosmotic to B.
● Hyposmotic solutions: when solution A has less solute particles than B, solution A is
hyposmotic to B.
● Tonicity: is used to compare two fluid compartments, refers to the concentration of
non-penetrating solutes only and is always comparative. This can be estimated but
not measured directly.
● General concepts:
○ The two fluid compartments of the body, intracellular fluid (ICF) and
extracellular fluid (ECF), are in osmotic balance.
○ Water moves by facilitated diffusion through aquaporin channels across most
cell membranes. This process is called osmosis.
○ Non-permeable solutes are called effective solutes. Cellular volume is
critically dependent on the steady state of effective solutes and water across
the cell membrane in exchange with the extracellular fluid compartment.
○ Cells shrink in hypertonic ECF conditions and swell in hypotonic ECF
conditions.
● Problems:
1. Bob ate an anchovy pizza (very salty) during the super bowl but had nothing
to drink. Did this meal alter the size of his ECF compartment? Why or why
not?
2. Mark tried to pass his kidney stone by drinking 6 liters of water over 1 hour.
His wife became concerned when he became confused and disoriented. At
the ER, they were told that Mark had lowered (diluted) the sodium
concentration of his IS compartment to 123 mOsM. Did the osmolarity of the
IVS change? When the IS becomes hypotonic, does this affect the volume of
brain cells (neurons)?
3. John ran a marathon. How did his profuse sweating (loss of hyposmotic
water) affect the osmolarity of the ECF (increase, decrease, remain
unchanged)? Did the ECF volume increase, decrease, or remain unchanged?
Was there a change in water distribution between ECF and ICF
compartments?
● Answers:
1. Yes, the ECF compartment increased. Due to an increase in osmolarity, water
moved into the ECF from the ICF.
2. Yes, the sodium concentration in the IVS decreased to 123 mOsM. If the IS
becomes hypotonic to a cell, then water enters the cell causing the cell to
swell. Lowering the extracellular sodium concentration decreases the
electrochemical gradient (i.e., makes it more negative).
3. Osmolarity of ECF increases because the sweat lost is hyposmotic fluid. ECF
volume decreases because total body water decreases. Yes, the ECF volume
 decreases which raises the osmolarity of the ECF. Water moves from the ICF
to the ECF to “restore” osmotic equilibrium.
ENDOCRINE SYSTEM
GENERAL CONCEPTS:
● The endocrine system is one of the major homeostatic control systems of the body.
● Homeostatic control:
○ Paracrine: chemical secreted by a cell that will work on a neighbor cell.
○ Autocrine: chemical that will work on the cell that secreted it.
● Endocrine system and homeostatic control:
○ A cell secretes its chemical into the blood and the blood will take it to the
target cells, those that have the specific receptors for the chemical
(hormones).
● Target cells of the endocrine system have a high affinity receptor since the chemical
will be highly diluted in the blood (very low concentration).
● Endocrine glands:
○ Ductless glands whose secretions (hormones) are delivered by the blood to
target tissues.
○ They regulate many of the homeostatic missions of the body.
■ Sodium and water balance.
■ Calcium balance.
■ Energy balance.
■ Processes that cope with stress.
■ Growth and development.
■ Processes associated with reproduction.
● Concentration of hormones in blood:
○ Rate of production:
■ Most regulated aspect.
■ Mediated by positive and negative feedback loops.
○ Rate of delivery:
■ Dependent on perfusion and blood flow → slow delivery.
■ Following mass action laws (carriers), some hormones are bound to
the carrier, then it can come off from the carrier and become a free
agent and is able to bind to the receptor at the target cell.
○ Rate of degradation and / or excretion.
● Peptide/protein hormones:
○ Composed of 3 amino acids or more.
○ Soluble in blood.
○ Synthesized on the rough endoplasmic reticulum as preprohormones, they
are inactive.
○ Once it is in the golgi the preprohormone is cleaved into a prohormone, they
are sometimes also inactive.
○ Then still in the golgi, the prohormones will be packed into secretory vesicles.
○ Once it is packed, the prohormone will finally be cleaved into a peptide
hormone (active).
○ The secretory vesicle with the hormone will stay inside the cell until the cell
receives a signal to release it.
○ Once in the blood they have short half lives and they do not require carriers.
○ Example: insulin.
● Steroid hormones:
○ Made by adrenal glands, gonads and placenta.
○ Derivate from cholesterol.
○ Insoluble in plasma (blood fluid) so need to be transported by carrier proteins.
○ Synthesized and secreted on demand.
○ Conversion to a more active version in target tissues.
● Amino acid derivatives hormones:
○ Example: derivatives from Tyrosine.
■ Epinephrine: produced in adrenal glands, soluble in plasma and short
half life.
■ Thyroxine: Insoluble in plasma, transported via carrier, long half life,
conversion in target tissues.
○ Thyroid hormones and catecholamines.
● Transport carriers:
○ Extends half life of hormones in the blood.
○ Sequester hormone from its target cell receptor. When the hormone is
connected to the carrier it can not act upon the target cell.
○ Total concentration in blood = free + bound (only free is active).
● Receptor types:
○ Integral membrane proteins (for peptide hormones) .
○ Some hormones, such as Steroid and Thyroid hormones, are soluble in lipids
and can cross the membrane by simple diffusion, therefore their receptors are
located inside the cell on the cytoplasm.
○ Target cells can have more than one type of receptor and there is a big
number of them.
 ● Target cell sensitivity depends on receptors.
○ Affinity to hormone: for ½ maximal response, high affinity = low (hormone)
needed.
○ Receptor number: cells with more receptors are more sensitive to hormones.
○ Competition: binding by another agonist (or antagonist) reduces sensitivity.
○ Saturation; hormone concentration when all receptors are bound.
● Inactivation of hormone signaling.
○ Receptor desensitization: turn off the system at the gland itself.
■ Sequestration: remove the receptor from the cell surface.
■ Degradation: remove receptor from cell and degrade it.
○ Negative feedback:
■ Removes initial stimulus, so hormones will not be secreted.
● General concepts:
○ Peptide hormones are soluble in plasma, bind cell surface receptors, are
fast-acting and short-lived.
○ Thyroid hormones and steroid hormones are insoluble in plasma, act via
intracellular receptors to change transcription, are slow-acting and long-lived.
○ Binding proteins (carriers) regulate hormone availability, physiology function
and extend half lives.
○ Hormone release is under neural, hormonal, nutrient and ion regulation.
○ Signaling is regulated by changing plasma hormone concentration and by
changing target cell receptor sensitivity.
ASSESSMENT AND PATHOLOGY:
● Assessment of function:
○ Too much: hyper secretion, hormone excess, this can desensitize the
receptors at the target cell making them not recognize the hormone and not
respond or a really strong response.
○ Too little: hypo-secretion, hormone insufficiency, do not get the biological
response wanted or needed.
 ○ Target cell resistance: unresponsive, the receptors are either removed or
degraded.
○ Just right: normal or eu-secretion, works fine.
● Competitive binding assay:
○ Measure hormones.
○ The binding of a ligand labeled with a fluorescent or radioactive tag is typically
measured at a single concentration in the presence of varying concentrations
of an unlabeled, competing ligand.
● Bioassay:
○ To know if hormones are functional.
○ Bioassays involve administering the test substance to a living organism to
determine the substance‫׳‬s pharmacological activity.
● General concepts:
○ Pathology in endocrinology occurs when there is either too little or too much
hormone or resistance to the hormone due to receptor dysfunction.
○ Interpretation of hormone levels requires consideration of either the trophic
hormone(s) or of the ion/nutrient controlled by the hormone.