Accumulation of fluid in the interstitial compartment, which usually leads to a visible swelling of the affected tissue.

Facilitated diffusion (or facilitated transport) is a form of passive transport across biological membranes and refers to carrier-mediated transport of molecules/ions down a concentration gradient. Facilitated transport is mediated by facilitative transporters (also referred to as uniporters).

Facilitated Diffusion

Refers to synaptic or receptor potentials that can vary in amplitude and direction. Graded potentials can be depolarizing or hyperpolarizing and do not have a threshold.

Action potential

Neuronal Action Potential - Introduction
Neuronal Action Potential - Graded Potentials versus Action Potentials

Secondary active transport

Secondary active transport

A condition associated with hypothyroidism (especially primary hypothyroidism) in adults. It is characterized by thick, course skin, skin swelling (edema), and decreased metabolic rate and mental activity.

The A band is the region of a striated muscle sarcomere that contains myosin thick filaments. In fact, the A band is the entire length of the thick filament of the sarcomere. Its length is approximately 1 μm. The center of the A band is located at the center of the sarcomere (M line).

H zone
I band
M line
Z disk

The absolute refractory period refers to a period during the action potential. This is the time during which another stimulus given to the neuron (no matter how strong) will not lead to a second action potential. The absolute refractory period starts immediately after the initiation of the action potential and lasts until after the peak of the action potential. Following this period, the relative refractory period begins.

Relative refractory period

Neuronal Action Potential - Refractory Periods

ACh

Acetylcholine (ACh) is a chemical neurotransmitter used by the central nervous system (CNS) as well as the peripheral nervous system (PNS). Acetylcholine is a classical neurotransmitter and, in fact, it was the first of the classic neurotransmitters to be discovered. It was discovered in 1914 by Henry Hallett Dale while conducting experiments on the heart.

Acetylcholine is the neurotransmitter used by the somatic division of the nervous system at the neuromuscular junction (where a somatic motor neuron makes synaptic contact with a skeletal muscle cell). Acetylcholine is also used extensively by both branches of the autonomic nervous system; sympathetic and parasympathetic. It is the primary neurotransmitter released in autonomic ganglia by preganglionic autonomic neurons. It is also the primary neurotransmitter released by parasympathetic postganglionic neurons. A few sympathetic postganglionic neurons also release acetylcholine. The diverse actions of acetylcholine are exerted via the activation of nicotinic and muscarinic ACh receptors.

Acetylcholine (Wikipedia)

The action potential is a rapid and reversible reversal of the electrical potential difference across the plasma membrane of excitable cells such as neurons, muscle cells and some endocrine cells. In a neuronal action potential, the membrane potential rapidly changes from its resting level of approximately -70 mV to around +50 mV and, subsequently, rapidly returns to the resting level again. The neuronal action potential forms an important basis for information processing, propagation, and transmission. In muscle cells, the action potential precedes, and is necessary to bring about, muscle contraction. Some endocrine cells also exhibit action potentials, where the excitation leads to hormone secretion.

The action potential is also referred to as the electrical impulse or nervous impulse.

Graded potential

Neuronal Action Potential

An early sexual maturation stage, occurring 1 or 2 years before the onset of puberty, during which the zona reticularis of the adrenal cortex releases increased levels of dehydroepiandrosterone (DHEA) and androstenedione. These adrenal androgens are ultimately responsible for the appearance of pubic and axillary hair, increased oil production by facial skin, acne, and distinct adult body odor.

Menarche
Pubarche
Thelarche

Leading toward a region or structure of interest.

In the nervous system, afferent fibers (i.e., neurons) transmit information from a peripheral receptor to the spinal cord or the brainstem. Afferent neurons are also referred to as sensory neurons.

In the kidneys, the afferent arteriole carries blood to the glomerular capillaries.

Efferent

An agonist is a molecule that binds to a receptor and activates a physiological response similar to that induced by the naturally occurring physiological ligand of the receptor. Therefore, agonist binding to a receptor mimics the action of the natural ligand.

For example, acetylcholine (ACh) is the naturally occurring physiological ligand that activates nicotinic and muscarinic acetylcholine receptors. Nicotine is an agonist of nicotinic ACh receptors (nAChR), and muscarine is an agonist of muscarinic ACh receptors (mAChR).

Antagonist

All-or-nothing is usually used when describing the action potential. It refers to the well-known observation that an action potential always occurs in its full size (i.e., full magnitude of voltage change).

Many physiologists use all-or-nothing and all-or-none interchangeably.

Important Features of the Neuronal Action Potential

Amiloride inhibits epithelial Na⁺ channels (ENaC), and in doing so, it acts as a diuretic by inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the kidneys.

Amiloride (Wikipedia)

A negatively charged ion.

Cation

An antagonist is a molecule that binds to a receptor, however, it does not activate the physiological response induced by the naturally occurring physiological ligand of the receptor. Moreover, once bound to the receptor, an antagonist prevents the physiological ligand from activating the receptor. Therefore, antagonist binding to a receptor prevents or blocks the action of the natural ligand.

For example, acetylcholine (ACh) is the naturally occurring physiological ligand that activates nicotinic and muscarinic acetylcholine receptors. Tubocurarine and succinylcholine are antagonists of the nicotinic ACh receptor (nAChR), and atropine is an antagonist of the muscarinic ACh receptor (mAChR).

Agonist

Without a nucleus. In particular, it refers to a cell that lacks a nucleus. For example, prokaryotic cells are anucleate. In addition, red blood cells (erythrocytes) are anucleate.

The large blood vessel (artery) that receives the output of the left ventricle of the heart. The aorta is the first and largest (in diameter) artery of the systemic circulation.

Following ventricular contraction (systole), hydrostatic pressure within the ventricle exceeds the pressure in the aorta, which forces blood out of the left ventricle, through the aortic semilunar valve, and into the aorta. As the ventricle relaxes during diastole, the pressure within the left ventricle drops to a level below that in the aorta. At this point, the aortic semilunar valve closes, which prevents the backflow of blood from the aorta to the left ventricle.

The region of the neuron cell body from which the axon originates. The axon hillock is generally the site of action potential initiation. It is also referred to as the initial segment.

Proposed model for the inactivation of some voltage-gated ion channels. According to this model, after channel opening, the pore of the open channel is plugged by a globular cytoplasmic portion of the channel protein. The globular portion (ball of amino acids) is tethered to the rest of the protein by a linker part (chain of amino acids).

Channel inactivation

Neuronal Action Potential - Important Features of the Neuronal Action Potential

Concave on both sides of a structure, usually referring to a disc or a lens.

Of particular importance to physiology is the structure of mature red blood cells (erythrocytes), which is a flattened cell that has assume a biconcave shape. It is thought that the biconcave shape of red blood cells helps with the flow property of blood through blood vessels.

BMI

The body mass index is measured by dividing body weight (in kilograms) by body height (in meters) squared (kg / m²). It is highly correlated with body composition, and higher BMI values are correlated with higher body fat content. The BMI value is used to classify one's weight in several categories including underweight, normal, overweight, and obese. The range of BMI values considered to be normal is 18.5 to 24.9. Higher BMI values are associated with an increased risk for diseases such as diabetes mellitus type II, hypertension, and cardiovascular disease.

Body Mass Index Calculator

Body mass index (Wikipedia)

Another name for the parafollicular cell type within the thyroid gland. C cells are situated outside of the thyroid follicles and are interspersed between the follicles. C cells are responsible for producing the hormone calcitonin.

Parafollicular cell

CO

Cardiac output is defined as the volume of blood pumped every minute by each (left or right) ventricle of the heart. It is generally reported in L/min or mL/min.

Cardiac output (CO) is the product of heart rate (HR) and stroke volume (SV). Thus,

CO = HR × SV

Heart rate is defined as the number of heart contractions per minute. Stroke volume is the volume of blood pumped per ventricular contraction.

For a typical resting adult human being at rest, CO is approximately 5 L/min.

CO = 70 contractions/min × 70 mL/contraction = 4,900 mL/min

Thick connective tissue that separates the atria and the ventricles. It is also referred to as fibrous skeleton of the heart. Despite its name, it is important to note that there is no bone in this tissue.

A positively charged ion.

Anion

The lowest part of the female uterus facing the vaginal canal. It is cylindrical in shape and 2-3 cm long. A cervical canal runs the entire length of the cervix and connects the lumen of the vaginal canal to the lumen of the uterus. The opening of cervical canal into the uterus is called the internal os, and the opening into the vagina is called the external os.

Refers to a conformational change of a channel protein by which the channel goes from the open state to the inactive state. The inactive state refers to a conformational state in which ions are not allowed to permeate the channel pore. Thus, with respect to ion permeability, the inactive state is similar to the close state of the channel. Ions cannot permeate the channel pore either in the closed or inactive state. However, the channel assumes very distinct and different conformations in the inactive state and closed state.

Neuronal Action Potential - Important Features of the Neuronal Action Potential

An integral membrane protein which contains a pore through which ions, water, or polar molecules permeate. For any given channel, the pore is usually very selective for the particular ion or molecule. For example, sodium (Na⁺) channels are very selective for Na⁺ over other cations.

The channel pore may be constitutively open, or it may be gated to the open state by various stimuli such as chemical ligands, voltage, temperature, or mechanical stimulation of the membrane.

Refers to the concentration gradient of an ion or molecule. The concentration gradient may exist across a biological membrane, where the concentration is higher on one side of the membrane compared to the other side. Concentration gradient may also exist in a solution without an apparent barrier separating the area of higher concentration from the area of lower concentration. In both cases, the free energy that results from the concentration difference drives the movement of the ion/molcule from the area of higher concentration to the area of lower concentration. In free solution, the ion/molecule simply diffuses down its gradient. Movement across a biological membrane is more complicated and is a function of lipid solubility of the ion/molecule as well as the presence of channels or transport proteins that can allow the ion/molecule to cross the membrane (see Lipid Bilayer Permeability and Summary of Membrane Transport Processes).

Electrical gradient
Electrochemical gradient

CI⁻

The main anion (negatively charged ion) of the extracellular fluid.

Cloride (Cl⁻) plays an important role in several physiological processes such as the action potential of skeletal muscle cells, CO₂ transport in blood (via Cl⁻/bicarbonate exchange across the plasma membrane of red blood cells), and many other processes.

The extracellular concentration of Cl⁻ is about 110 mM. The intracellular concentration of Cl⁻ is about 10 mM.

Refers to neurons, synapses, or receptors where acetylcholine is used as the neurotransmitter.

For example, cholinergic neurons release acetylcholine as their neurotransmitter.

In cholinergic synapses, acetylcholine is released from the presynaptic neuron, and it acts on acetylcholine receptors in the plasma membrane of the postsynaptic cell.

Cholinergic receptors are those that respond to acetylcholine as the physiological ligand. The two major types are nicotinic and muscarinic cholinergic receptors (may also be referred to as nicotinic and muscarinic acetylcholine receptors).

Cholinergic drugs are compounds that mimic the action of acetylcholine by binding to and activating cholinergic receptors.

The semi-solid, partially-digested contents of the stomach that exit via the pyloric valve to enter the duodenum (initial region) of the small intestine.

Coiled, fluid-filled cavity within the bony labyrinth of the inner ear, where the hearing (auditory) structures of the inner ear are located. The cochlea contains the Organ of Corti.

Organ of Corti

The colon is part of the large intestine within the digestive tract that is located between the cecum and the rectum. The colon is subdivided into the ascending colon, transverse colon, descending colon, and sigmoid colon.

A type of secondary active transport across a biological membrane in which a transport protein couples the movement of an ion (usually Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

In cotransport, the direction of transport is the same for both the driving ion and driven ion/molecule (into the cell or out of the cell).

An example is the Na⁺/glucose cotransporter (SGLT), which couples the movement of Na⁺ into the cell down its electrochemical gradient to the movement of glucose into the cell against its concentration gradient.

Cotransport is also commonly referred to as symport.

Transport proteins that are involved in this type of transport are referred to as cotransporters or symporters.

Symport

Secondary active transport
Exchange

Lecture notes on Secondary Active Transport

Mental retardation, dwarfism, and abnormal bone formation caused by thyroid hormone deficiency during fetal development.

An electrophysiological technique in which the current passing across the cell membrane is controlled experimentally, and the membrane voltage is measured.

Voltage clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

The flow of charge. In electrical wires and electronic circuits, current is carried by electrons. In physiological solutions, current is carried by ions in solutions.

Voltage

Leading away from a region or structure of interest.

In the nervous system, efferent fibers (i.e., neurons) transmit information from the central nervous system to peripheral effector organs (i.e., muscles or glands). Therefore, the cells bodies of efferent neurons reside within the central nervous system, whereas their axonal projections exit the central nervous system to make synaptic contact with effector organs in the periphery. Efferent neurons are also referred to as motor neurons.

In the kidneys, the efferent arteriole carries blood away from the glomerular capillaries.

Afferent

Movement of a substance out of the cell.

Efflux is reported as a rate. It is the amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Influx
Unidirectional flux
Net flux

ECG or EKG

A recording of the electrical activity of the heart measured by placing multiple (3 to 10) electrodes on the surface of the skin.

V_DF

When an ion is not at its electrochemical equilibrium, an electrochemical driving force (V_DF) acts on the ion, causing the net movement of the ion across the membrane down its own electrochemical gradient.

The electrochemical driving force is generally expressed in millivolts and is calculated according the following equation:

V_DF = V_m − V_eq

where V_DF is the electrochemical driving force, V_m is the membrane potential, and V_eq is the equilibrium potential.

Membrane potential
Equilibrium potential
Electrochemical gradient

Resting Membrane Potential - Electrochemical Driving Force Acting on Ions
Electrochemical Driving Force Calculator

Electrogenic pumps are primary active transporters that hydrolyze ATP and use the energy released from ATP hydrolysis to transport ions across biological membranes leading to the translocation of net charge across the membrane.

For example, the Na⁺/K⁺ ATPase (sodium pump) is an electrogenic pump because during every transport cycle, it transports 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell. This leads to the movement of one net positive charge out of the cell making this process electrogenic.

Electrogenic

An electrogenic transport process is one that leads to the translocation of net charge across the membrane. For example, ion channels such as Na⁺, K⁺, Ca²⁺, and Cl⁻ channels are electrogenic.

The Na⁺/K⁺ ATPase is electrogenic because for every ATP molecule hydrolyzed, 3 Na⁺ ions are transported out of the cell and 2 K⁺ ions are transported into the cell (leading to the translocation of one net positive charge out of the cell).

Many secondary active transporters are also electrogenic. For example, the Na⁺/glucose cotransporter (found in the small intestine and kidney proximal tubules), transports 2 Na⁺ ions and 1 glucose molecule into the cell across the plasma membrane (leading to the translocation of two net positive charges into the cell per transport cycle).

Electrophysiology is the study of the electrical properties of biological macromolecules, cells, tissues, and organs. Electrical signals such as voltage and/or current are generally measured. Examples include measuring changes in the membrane voltage of excitable cells (e.g., neurons, muscle cells, and some endocrine cells) during an action potential. The current carrried by ions as they permeate the pore of ion channels can also be measured - both at the single-channel level (single-channel current), as well as the macroscopic current resulting from the activity of a population of channels. As another example, electrical measurements may involve recording voltage changes at the surface of the skin that result from the activity of skeletal muscles (electromyogram, EMG), cardiac myocytes (electrocardiogram, ECG), or neurons in the brain (electroencephalogram, EEG).

Endocrine cells are responsible for producing and releasing hormone molecules into the bloodstream. Endocrine cells are typically grouped together in organs referred to as endocrine glands.

Endocrine gland
Hormone

Endocrine glands contain clusters of endocrine cells, whose function is to is to release hormones into the bloodstream.

Endocrine glands are ductless glands in that their secretions do not enter a duct (as for example with salivary glands). Rather, endocrine glands release their secretions (i.e., messenger molecules) into the interstitial fluid in highly vascularized regions, where the molecules then enter the bloodstream. The chemical messenger molecule that is released into the bloodstream is referred to as a hormone.

Endocrine cell
Hormone

A type of secondary active transport across a biological membrane in which a transport protein couples the movement of an ion (usually Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

In exchange, the driving ion and the driven ion/molecule are transported across the biological membrane in opposite directions.

An example is the Na⁺/Ca²⁺ exchanger (NCX), which couples the movement of 3 Na⁺ ions into the cell down its electrochemical gradient to the movement of 1 Ca²⁺ ion out of the cell against its electrochemical gradient.

Exchange is also commonly referred to as antiport.

Transport proteins that are involved in this type of transport are referred to as exchangers or antiporters.

Antiport

Secondary active transport
Cotransport

Lecture notes on Secondary Active Transport

Refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin-releasing pancreatic β cells) are excitable cells.

Resting Membrane Potential - Introduction

Protrusion or bulging of one or both eyeballs out of the orbit. It may be caused by swelling of orbital tissue in response to trauma, or by hyperthyroidism (especially primary hyperthyroidism).

It is also referred to as exophthalmus, exophthalmia, proptosis, or exorbitism.

Exophthalmos (Wikipedia)

The rate of movement of a substance across an interface. The interface could be the plasma membrane (separating the intracellular or extracellular fluid compartments), an epithelial sheet separating two compartments, or where two solutions of different composition meet.

Flux is reported as a rate. It is the amount of substance that moves across a given interface per unit time.

Influx
Efflux
Unidirectional flux
Net flux

Milk or milky discharge from the breasts that is not associated with childbirth or breastfeeding (nursing).

Also spelled galactorrhoea.

GABA

GABA is an inhibitory amino acid neurotransmitter in the central and peripheral nervous systems. It is the most abundant inhibitory neurotransmitter in the nervous system. During embryonic development, GABA acts as an excitatory neurotransmitter at some central synapses. GABA is a classical neurotransmitter. Its action is exerted via the activation of GABA_A, GABA_B, and GABA_C receptors. GABA_A and GABA_C receptors are ligand-gated chloride channels, whereas GABA_B receptors are G protein coupled receptors. At GABAergic synapses, the action of GABA is terminated by GABA transporters (GAT), which transport GABA from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

Excretion of glucose in urine. This is indicative of an abnormal condition such as hyperglycemia caused by diabetes mellitus.

Glutamate (Glu, E) is one of the standard twenty (20) amino acids used by cells to synthesize peptides, polypeptides, and proteins. It has a molecular weight of 147.13 g/mol. Its side chain has a pK_a of 4.07 and, therefore, glutamate has a net negative charge at physiological pH.

In the nervous system, glutamate is an excitatory amino acid neurotransmitter. In fact, glutamate is the most abundant excitatory neurotransmitter in the nervous system. Glutamate is a classical neurotransmitter. Its action is exerted via the activation of glutamate receptors (GluR), some of which are ligand-gated ion channels (ionotropic receptors), and some are G protein coupled receptors (GPCRs, metabotropic receptors). At glutamatergic synapses, the action of glutamate is terminated by glutamate transporters (EAAT, excitatory amino acid transporter), which transport glutamate from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

Glycine (Gly, G) is one of the standard twenty (20) amino acids. At a molecular weight of 75.07 g/mol, it is the smallest of the 20 amino acids used by cells to synthesize peptides, polypeptides, and proteins.

In the nervous system, glycine is also an inhibitory amino acid neurotransmitter. Glycinergic synapses are most commonly found in brain stem and spinal cord circuits. Glycine is a classical neurotransmitter. Its action is exerted via the activation of ionotropic glycine receptors (GlyR), which are ligand-gated chloride channels. At glycinergic synapses, the action of glycine is terminated by glycine transporters (GlyT), which transport glycine from the extracellular space in synaptic and extrasynaptic regions into neurons and glia.

Goiter is an enlargement of the thyroid gland caused most commonly by iodine deficiency in the diet. Iodine deficiency leads to low levels of thyroid hormone production, and a reduction in thyroid hormone negative feedback on the hypothalamus and the anterior pituitary leads to a compensatory rise in the thyroid stimulating hormone (TSH). Enlargement of the thyroid gland is, therefore, caused by abnormally high circulating levels of TSH, which has a strong trophic effect on the thyroid gland.

Hairy. Particularly refers to excessive or unwanted hair on the face and body.

Hirsutism

Abnormal, unwanted, and excessive hair growth on the face and body. Particularly used to refer to women with such a condition.

Hirsute

The Hodgkin cycle represents a positive feedback loop in neurons, where an initial membrane depolarization from the resting value (∼ −70 mV) to the threshold value (∼ −50 mV) leads to rapid depolarization of the membrane potential to approach the equilibrium potential for Na⁺ (V_Na ≈ +60 mV). The voltage-gated Na⁺ channels of neurons are responsible for the Hodgkin cycle.

See the figure depicting the Hodgkin cycle.

Important Features of the Neuronal Action Potential

A chemical messenger molecule secreted (i.e., released) by endocrine cells within endocrine glands.

By definition, a hormone molecule is released into the bloodstream and travels throughout the body to find its target cells. Teget cells may be within the intravascular compartment (i.e., within blood vessels), but most hormones have target cells in tissues outside of the blood vessels.

Endocrine cell
Endocrine gland

A condition characterized by an inability to tolerate, or over-sensitivity to, sounds of moderate loudness encountered in daily life.

It is also spelled hyperacousis.

Hyperacusis (Wikipedia)

Condition in which the plasma glucose concentration is abnormally high. In general, a fasting plasma glucose concentration higher than 110 mg/dL, or a postprandial plasma glucose concentration higher than 180 mg/dL is considered abnormally high.

Normal, fasting glucose concentrations range from 70 to 110 mg/dL.

Hyperglycemic
Hypoglycemia
Hypoglycemic

Related to, or pertaining to hyperglycemia.

An agent that causes an increase in plasma glucose concentration (i.e., induces hyperglycemia).

Hyperglycemia
Hypoglycemia
Hypoglycemic

Excessive appetite or consumption of food. It may be associated with damage to the hypothalamus. Also referred to as polyphagia.

Refers to the hyperpolarization phase of the action potential.

It is also referred to as undershoot.

See figure.

Hyperpolarization

Important Features of the Neuronal Action Potential

Hyperthyroidism refers to a pathophysiological condition in which the thyroid gland produces and releases abnormally high levels of the thyroid hormones (T₃ and T₄).

The symptoms of hyperthyroidism may include high metabolic rate, weight loss, nervousness, excess heat production, tachycardia, and tremor.

Two main forms of hyperthyroidism exist: (1) Primary hyperthyroidism, and (2) Secondary hyperthyroidism.

In primary hyperthyroidism, the thyroid gland produces high levels of the thyroid hormones, either as a result of a secretory tumor of the thyroid gland, or under the control of thyroid stimulating immunoglobulins (such as in Graves' disease).

Secondary hypothyroidism is caused by high levels of thyroid stimulating hormone (TSH) produced by the anterior pituitary gland. TSH then stimulates the thyroid gland to produce excessive amounts of the thyroid hormones.

Hypothyroidism
Euthyroidism

Condition in which the plasma glucose concentration is abnormally low. In general, a plasma glucose concentration lower than 70 mg/dL is considered abnormally low.

Normal, fasting glucose concentrations range from 70 to 110 mg/dL.

Hypoglycemic
Hyperglycemia
Hyperglycemic

Related to, or pertaining to hypoglycemia.

An agent that causes a reduction in plasma glucose concentration (i.e., induces hypoglycemia).

Hypoglycemia
Hyperglycemia
Hyperglycemic

Underactivity of the anterior pituitary gland characterized by reduced secretion of anterior pituitary hormones.

Hypothyroidism refers to a pathophysiological condition in which the thyroid gland does not produce sufficient amounts of the thyroid hormones (underactive thyroid), leading to abnormally low levels of the thyroid hormones (T₃ and T₄).

The symptoms of hypothyroidism may include reduced metabolic rate, chronic fatigue, weight gain, myxedema, and depression.

Three main forms of hypothyroidism exist: (1) Primary hypothyroidism, (2) Secondary hypothyroidism, and (3) Tertiary hypothyroidism.

In primary hypothyroidism, the thyroid gland itself is incapable of producing normal levels of the thyroid hormones.

Secondary hypothyroidism is caused by low levels of thyroid stimulating hormone (TSH). TSH, produced by the anterior pituitary gland, is required to stimulate the thyroid gland to produce the thyroid hormones.

Tertiary hypothyroidism is caused by low levels of thyrotropin releasing hormone (TRH). TRH, produced by the hypothalamus, is required to stimulate the anterior pituitary gland to produce TSH which, in turn, is required to stimulate the thyroid gland to produce the thyroid hormones.

Primary hypothyroidism
Secondary hypothyroidism
Tertiary hypothyroidism

Hyperthyroidism
Euthyroidism

A state of decreased total blood volume caused by blood loss, reduction in plasma volume, or other causes.

Decreased oxygen content in arterial blood.

Anoxia
Anoxemia
Hypoxia

Describes a condition in which there is a decrease in oxygen supply to tissues. It may be generalized (whole body) or local (e.g., brain).

Anoxia
Anoxemia
Hypoxemia

The I band is the region of a striated muscle sarcomere that contains thin filaments. This region is closest to the Z disk, and is the lightest region of the sarcomere when viewed in under the light or electron microscope. The I band is occupied by the thin filaments only. Each Z disk runs through the middle of the I band. Therefore, half of each I band belongs to one sarcomere, and the other half belongs to the neighboring sarcomere. The I band shortens as the muscle contracts and the sarcomere shortens.

A band
H zone
M line
Z disk

Movement of a substance into the cell.

Influx is reported as a rate. It is the amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Efflux
Unidirectional flux
Net flux

A glycoprotein released by parietal cells (also know as oxyntic cells) located in the fundus region of the stomach. Intrinsic factor is required for vitamin B₁₂ absorption in the small intestine.

In electrophysiological convention, a negative current value or downward deflection of a current trace is typically referred to as an inward current. A negative current value (i.e., inward current) can reflect either the movement of positive ions (cations) into the cell or negative ions (anions) out of the cell.

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

Refers to the ability of the thyroid gland to accumulate iodide (I⁻) against a steep electrochemical gradient. While the iodide concentration in plasma and interstitial fluid is approximately 300 nL, iodide concentration in the cytoplasm of thyroid follicular cells, as well as the lumen of thyroid follicles can be many folds higher. The protein that enables iodide transport into the thyroid gland against an electrochemical gradient is the Na⁺/iodide symporter (NIS), which is located in the basolateral membrane of thyroid follicular cells. Within the lumen of thyroid follicles, iodide is incorporated into the tyrosine residues of thyroglobulin during thyroid hormone biosynthesis, hence, allowing very high iodide concentrations in the colloid.

The tapping sounds heard through a stethoscope placed over a partially compressed peripheral artery.

For the purpose of non-invasive blood pressure measurements, the stethoscope is usually placed on the skin overlying the brachial artery just distal to an inflated pressure cuff wrapped around the upper arm. As the pressure cuff is gradually deflated, the Korotkoff sounds result from the pulsations of the blood through the partially constricted brachial artery. With each ventricular systole, blood is forced to flow through the partially constricted brachial artery, and the turbulence in blood flow leads to the generation of the Korotkoff sounds. When the pressure cuff is fully deflated, flow through the artery resumes its normal laminar flow and, at that time, the Korotkoff sounds disappear.

Lidocaine is a local anesthetic and an antiarrhythmic drug. It is a commonly used local anesthetic for minor surgery and in dental procedures. Lidocaine is also used topically to relieve itching, burning, and pain from skin inflammations.

Lidocaine's mechanism of action is to block fast voltage-gated Na⁺ channels of neurons and cardiac myocytes.

Other names used for lidocaine are xylocaine and lignocaine.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Lidocaine (Wikipedia)

In striated muscle sarcomere, the M line is the attachment site for the thick filaments. The M line is in the center of the A band and, thus, it is in the center of the sarcomere.

A band
H zone
I band
Z disk

A motor unit is composed of a motor neuron and all of the muscle fibers (i.e., muscle cells) it innervates.

Alternatively, a motor unit is a group of muscle fibers innervated by a single motor neuron.

Plasma membrane of a muscle cell. It is also referred to as sarcolemma.

Sarcolemma

Cytoplasm of a muscle cell. It is also referred to as sarcoplasm.

Sarcoplasm

Newly synthesized or in the process of being synthesized

An equation used to calculate the equilibrium potential (V_eq.) of an ion. The equilibrium potential for an ion is also referred to as the Nernst potential for that ion. It is the membrane potential at which no net movement of the ion in question occurs across the membrane.



where V_eq. is the equilibrium potential, R is the universal gas constant, T is the temperature in Kelvin, z is the valence of the ionic species, F is the Faraday's constant, and [X]_o and [X]_i are the extracellular and intracellular, respectively, concentrations of the ion in question.

Resting Membrane Potential - Nernst Equilibrium Potential
Derivation of the Nernst Equation

Refers to the action potential of neurons. It is also referred to as the nervous impulse.

Action potential

Neuronal Action Potential

Refers to the action potential of neurons. It is also referred to as the nerve impulse.

Action potential

Neuronal Action Potential

Net flux represents the amount of substance moved in or out of the cell. It is the mathematical difference between influx and efflux.

Net flux = Influx − Efflux

Similar to influx and efflux, net flux is reported as a rate. It is the net amount of substance that moves through a given area of the plasma membrane per unit time.

Flux
Influx
Efflux
Unidirectional flux

Neurohormones are chemical messenger molecules that are released by neurons, but enter the bloodstream where they travel to distant target sites within the body. Therefore, neurohormones share characteristics with both neurotransmitters and hormones. Similar to neurotransmitters, neurohormones are released by neurons. Similar to hormones, neurohormones travel in the bloodstream.

Two well-known examples of neurohormones are oxytocin and the antidiuretic hormone (also referred to as vasopressin).

Hormone
Neurotransmitter

Neurotoxins are chemical molecules that have an adverse effect on neuron function and, thus, disrupt the normal function of the nervous system. Neurotoxins could be small molecules or peptides and can be derived from a variety of invertebrate and vertebrate animals, as well as plant species.

The following is a short list of some examples of neurotoxins:

α-Bungarotoxin: A peptide neurotoxin that inhibits the nicotinic acetylcholine receptor.

Chlorotoxin: A peptide neurotoxin that inhibits chloride channels.

α-Conotoxin: A peptide neurotoxin that inhibits the nicotinic acetylcholine receptor.

δ-Conotoxin: A peptide neurotoxin that inhibits voltage-gated sodium channels.

w-Conotoxin: A peptide neurotoxin that inhibits N-type voltage-gated calcium channels.

Picrotoxin: Inhibits GABA_A receptor chloride channels.

Tetrodotoxin: Inhibitor of neuronal voltage-gated sodium channels.

Chemical messenger molecules released by neurons into the synaptic cleft.

Neurotransmitter molecules may be small molecules such as glutamate, γ-aminobutyric acid (GABA), acetylcholine, dopamine, norepinephrine, serotonin (5-hydroxytryptamine), and glycine. These are referred to as classic neurotransmitters. A neuron generally releases only one type of small classic neurotransmitter.

Neurotransmitters may also be peptide molecules, such as substance P, opioids, and somatostatin. These are referred to as neuropeptides.

Gas molecules, such as nitric oxide (NO), may also act as neurotransmitters.

Refers to an abnormally low volume of urine production. Generally, a urine production rate of less than 400 mL/day is referred to as oliguria.

Polyuria

Oliguria (Wikipedia)

Auditory sensory organ within the inner ear cochlea, where the inner and outer hair cells are located.

Cochlea

OAEs

Otoacoustic emissions (OAE) are sounds that arise from the organ of Corti within the cochlea of the inner ear in response to sound stimulation. They are thought to result from vibrations of cochlear outer hair cells (OHC) in response to stimulation by sound. Otoacoustic emissions are inaudible to the human ear, but can be recorded by placing a small recording device in the external auditory meatus (ear canal).

Otoacoustic emissions have clinical diagnostic value and are measured as part of hearing exams. In the newborn, otoacoustic emissions are recorded in order to detect blockage in the middle ear cavity (e.g., as a result of fluid accumulation) or external ear canal.

Ouabain binds to and inhibits the transport activity of the Na⁺/K⁺/ATPase (i.e., sodium pump).

Ouabain is plant derived and belongs to the class of drugs referred to as cardiac glycosides. Similar to other cardiac glycosides, ouabain increase heart muscle contractility. However, ouabain is used only experimentally and not in humans (as for example digoxin is for the treatment of congestive heart failure).

There is some evidence that ouabain may be produced endogenously in humans.

Vanadate

Ouabain (Wikipedia)

In electrophysiological convention, a positive current value or upward deflection of the current trace is typically referred to as an outward current. A positive current value (i.e., outward current) can reflect either the movement of positive ions (cations) out of the cell or negative ions (anions) into the cell.

Inward current

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

Body weight that exceeds the normal or standard weight range. The standard range is generally determined based on height and frame size.

Body Mass Index

Body Mass Index Calculator

The component of the electrocardiogram (ECG) that corresponds to the depolarization of atrial myocytes. Atrial depolarization precedes atrial contraction.

QRS complex
T wave

Cells within the thyroid gland. Parafollicular cells are situated outside of the thyroid follicles and are interspersed between the follicles. Parafollicular cells are responsible for producing the hormone calcitonin. Parafollicular cells are also referred to as C cells.

PCG

A recording of the sounds produced by the heart during the cardiac cycle. The main sounds recorded are those associated with turbulent blood flow caused by the closure of heart valves.

Glial cell found within the posterior pituitary gland. It resembles astrocytes and functions to provide support to unmyelinated axons whose terminals release oxytocin and vasopressin.

Plasma is the fluid portion of whole blood, which makes up about 40% to 60% of the total volume of whole blood. Plasma has a light yellow color and is generally obtained by separating the fluid portion from the blood formed elements through sedimentation or centrifugation. Plasma contains mostly water and, in addition, minerals, nutrients, proteins, hormones, and gases (oxygen and carbon dioxide). Unlike serum, in which fibrinogen and other clotting factors have been removed by coagulation, fibrinogen and other clotting factors remain present in plasma.

Plasma is one the main fluid compartments of the human body, making up nearly 10% of the total volume of body fluids. Plasma makes up the intravascular fluid compartment; itself a subcompartment of the extracellular fluid compartment.

Refers to an abnormally large volume of urine production. Generally, a urine production rate of higher than 2.5 L/day is referred to as polyuria.

Oliguria
Hypouresis

Polyuria (Wikipedia)

K⁺

The main cation (positively charged ion) of the intracellular fluid.

Potassium (K⁺) plays an important role in the action potential of neurons and muscle cells.

The extracellular concentration of K⁺ is about 4 mM. The intracellular concentration of K⁺ is about 150 mM.

Gradual hearing loss associated with aging.

Primary hypothyroidism is characterized by abnormally low levels of thyroid hormone (T₃ and T₄) production, where the defect is at the level of the thyroid gland itself.

In primary hypothyroidism, the circulating levels of the thyroid hormones are low, however, the levels of the thyroid stimulating hormone (TSH) are high due a lack of thyroid hormone negative feedback on the anterior pituitary.

Common causes of primary hypothyroidism include iodine deficiency (which leads to goiter), and Hashimoto's disease, in which autoimmune antibodies destroy the ability of the thyroid gland to produce the thyroid hormones.

Hypothyroidism
Secondary hypothyroidism
Tertiary hypothyroidism

A local topical anesthetic.

Procaine's mechanism of action is to block fast voltage-gated Na⁺ channels of neurons.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Procaine (Wikipedia)

Peptide hormone produced by the anterior pituitary gland. Prolactin is best known for its action in stimulating the mammary glands to produce milk (lactation).

Prolactin is known to be involved in many other physiological processes including enlargement of the mammary glands in preparation for milk production, sexual gratification, metabolism, regulation of the immune system, and others.

Prolactin (Wikipedia)

Pulse pressure is defined as the arithmetic difference between the systolic pressure (the highest blood pressure) and the diastolic pressure (the lowest blood pressure) recorded at any point along the vascular bed. Therefore:

Pulse pressure = Systolic pressure - Diastolic pressure

Pulse pressure values can be reported at any point along the vasculature starting from the left ventricle and aorta all the way to the vena cava and the right atrium. As with systolic and diastolic pressure values, pulse pressure is typically reported in mm Hg (millimeters of mercury). A typical arterial pulse pressure is 40 mm Hg (120 - 80 = 40 mm Hg). This value decreases as one proceeds along the vascular bed from arteries to arterioles, capillaries, venules, and veins. The most significant drop occurs along the arterioles.

Mean Arterial Pressure Calculator

The component of the electrocardiogram (ECG) that corresponds to the depolarization of ventricular myocytes. Ventricular depolarization precedes ventricular contraction.

P wave
T wave

The relative refractory period refers to a period during the action potential. This is the time during which a stronger than normal stimulus is needed in order to elicit an action potential. The relative refractory period immediately follows the absolute refractory period.

Absolute refractory period

Neuronal Action Potential - Refractory Periods

The voltage difference across a cell plasma membrane in the resting or quiescent state. It is also simply referred to as the resting potential (V_rest). The value of the resting membrane potential varies from cell to cell. Depending on the cell type, it can range from −90 mV to −20 mV.

For example, V_rest is −90 mV in skeletal and cardiac muscle cells as well as in astrocytes. In a typical neuron, V_rest is approximately −70 mV. In many non-excitable cells, V_rest ranges from −60 to −50 mV. In photoreceptors, V_rest is about −20 mV.

Resting membrane potential

Plasma membrane of a muscle cell. It is also referred to as myolemma.

Myolemma

Cytoplasm of a muscle cell. It is also referred to as myoplasm.

Myoplasm

Secondary active transport is a type of active transport across a biological membrane in which a transport protein couples the movement of an ion (typically Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

This transport process is referred to as active transport because the driven ion/molecule is transported against a concentration or electrochemical gradient. It is referred to as secondary active transport because no ATP hydrolysis is involved in this process (as opposed to primary active transport). The energy required to drive transport resides in the transmembrane electrochemical gradient of the driving ion.

Secondary active transport is also referred to as ion-coupled transport. Those utilizing Na⁺ as the driving ion are called Na⁺-coupled transporters. Those utilizing H⁺ as the driving ion are called H⁺-coupled transporters.

Two types of secondary active transport exist: cotransport (also known as symport) and exchange (also known as antiport). Na⁺/glucose cotransporter and H⁺/dipeptide cotransporter are examples of cotransporters. Na⁺/Ca²⁺ exchanger and Na⁺/H⁺ exchanger are examples of exchangers.

Cotransport
Symport
Exchange
Antiport

Lecture notes on Secondary Active Transport

Secondary hypothyroidism is characterized by abnormally low levels of thyroid hormone (T₃ and T₄) production, where the defect is at the level of the anterior pituitary gland.

In secondary hypothyroidism, the anterior pituitary gland is unable to produce sufficient levels of the thyroid stimulating hormone (TSH) which, in turn, leads to insufficient stimulation of the thyroid gland to produce the thyroid hormones (T₃ and T₄).

Thus, in secondary hypothyroidism, the circulating levels of both TSH and the thyroid hormones (T₃, and T₄) are abnormally low

Hypothyroidism
Primary hypothyroidism
Tertiary hypothyroidism

Secretion refers to cellular release of substances (ions and small and large molecules) to the external environment of the cell. Secretion may be accomplished by exocytosis (fusion of transport vesicles with the plasma membrane and release of vesicle contents to the external environment), by transport of molecules across the plasma membrane (via the activity of transport proteins such as pumps, transporters, and channels), or by simple diffusion of fat-soluble molecules through the plasma membrane out of the cell.

For example, endocrine cells secrete hormone molecules that then enter the bloodstream. Neurons release (i.e., secrete) neurotransmitter molecules into the synaptic cleft. Some neurons secrete neurohormones; which similar to hormones, travel in the bloodstream to reach distant target cells. Epithelial cells secrete molecules in luminal spaces, such as digestive enzymes secreted into the digestive tract by various cell types.

Excretion

Na⁺

The main cation (positively charged ion) of the extracellular fluid.

Sodium (Na⁺) plays an important role in several physiological processes such as the action potential of neurons and muscle cells, secondary active, sodium-coupled transport of ions, nutrients, neurotransmitters across the plasma membrane of cells, and many other processes.

The extracellular concentration of Na⁺ is about 145 mM. The intracellular concentration of Na⁺ is about 15 mM.

A rectangular signal waveform used in physiological studies to perturb (i.e., challenge) the system under study. The response of the system to the pulse is then studied carefully to learn about how the system responds to challenges.

Examples include pulses of voltage or current in electrophysiological experiments. Other examples include pulses of light, pressure, temperature, ligand, etc.

A square-wave pulse is defined by the amplitude and duration of the pulse, as well as by the frequency at which the pulse is applied to the system under study.

Neuronal Action Potential - Introduction

Square wave (Wikipedia)

Tachyphylaxis describes a condition where a person (or animal subject) develops rapid tolerance to a drug following a single or repeated administration of the drug. Therefore, higher doses of the drug may be needed to achieve the same response.

Tastants are taste-provoking chemical molecules that are dissolved in ingested liquids or saliva.

Tastants stimulate the sense of taste. It can also be said that tastants elicit gustatory excitation.

A tastant is the appropriate ligand for receptor proteins located on the plasma membrane of taste receptor cells.

In humans, taste buds are the sensory receptor areas primarily on the tongue, but also in the throat, where taste receptor cells are located. In humans, there are approximately 10,000 taste buds in the oral cavity (tongue) and throat. A typical human taste bud contains about 50 taste receptor cells. Stimulation of taste receptor cells by tastants elicits the sense of taste (also referred to as gustation).

Tertiary hypothyroidism is characterized by abnormally low levels of thyroid hormone (T₃ and T₄) production, where the defect is at the level of the hypothalamus.

In tertiary hypothyroidism, the hypothalamus is unable to produce sufficient levels of thyrotropin release hormone (TRH). Low TRH levels lead to low production of the thyroid stimulating hormone (TSH) by the anterior pituitary gland which, in turn, leads to insufficient stimulation of the thyroid gland to produce the thyroid hormones (T₃ and T₄).

Thus, in tertiary hypothyroidism, the circulating levels of TRH, TSH, T₃, and T₄ are all abnormally low.

Hypothyroidism
Primary hypothyroidism
Secondary hypothyroidism

TEA

An inhibitor of voltage-gated potassium (K⁺) channels.

TEA is a quaternary ammonium cation (positively charged ion). It is also commonly used as a cation replacement for sodium (Na⁺) in physiological buffers used in ion replacement experiments.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

TTX

Inhibitor of fast voltage-gated sodium (Na⁺) channels of neurons and muscle cells. It is an extremely potent and toxic neurotoxin.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Tetrodotoxin (Wikipedia)

The membrane voltage that must be reached in an excitable cell (e.g., neuron or muscle cell) during a depolarization in order to generate an action potential. At the threshold voltage, voltage-gated channels become activated. Threshold is approximately −50 to −40 mV in most excitable cells.

Sub-threshold
Supra-threshold

Neuronal Action Potential - Introduction

Tg

The major glycoprotein found within the colloid of thyroid follicles. The thyroid hormones (T₃ and T₄) are synthesized on the backbone of thyroglobulin.

Thyroid follicular cells are epithelial cells that form the lining of thyroid follicles. Each thyroid follicle is surrounded by a single layer of follicular cells. Follicular cells play the key role in thyroid hormone synthesis and release.

Thyroid follicular cells are also referred to as thyrocytes.

The condition of hearing a sound in the absence of an external sound stimulus. The sound may be ringing, buzzing, whistling, or hissing. The sound may be soft, loud, low-pitched, or high-pitched. It may be heard in one ear or both ears (simultaneously or independent of one another).

Tinnitus (Wikipedia)

Refers to the hyperpolarization phase of the action potential.

It is also referred to as hyperpolarizing afterpotential.

See figure.

Hyperpolarization

Important Features of the Neuronal Action Potential

The rate of movement of a substance across an interface in only one, and not the opposite, direction (i.e., flux in only one direction). For example, when referring to the plasma membrane of cells, we can think of unidirectional flux of a substance ino the cell (referred to as influx), as well as unidirectional flux of the substance out of the cell (referred to as efflux). The difference between two unidirectional fluxes is referred to as net flux, which is the net amount that moves into or out of the cell.

Flux
Influx
Efflux
Net flux

An inhibitor of the Na⁺/K⁺/ATPase (i.e., sodium pump). The form commonly used for this purpose is sodium orthovanadate.

Ouabain

Removal of approximately a pint of blood in a manner similar to that for donating blood. The procedure is generally used as a simple measure to reduce the number of circulating red blood cells (e.g., to treat polycythemia) or to reduce the amount of circulating iron (e.g., to treat hemochromatosis). The procedure may be repeated as needed.

It falls under procedures referred to as phlebotomy (removing blood for therapeutic or diagnostic purposes) or bloodletting (removing blood for therapeutic purposes).

An electrophysiological technique in which the voltage of a cell membrane is controlled experimentally, and the current passing across the membrane is measured.

Current clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

Areas of the central nervous system (brain and spinal cord) which consist mostly of myelinated axons (rather than cell bodies). The characteristic white color is due to the presence of myelin, which is mostly composed of lipids.

The part of the embryonic gonad that develops into the male reproductive ducts (epididymis, vas deferens, and seminal vesicles). In the female, this structure disappears because of the absence of anti-Müllerian hormone secreted by the Sertoli cells.