The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain (the medulla oblongata specifically). The brain and spinal cord together make up the central nervous system. The spinal cord begins at the Occipital bone and extends down to the space between the first and second lumbar vertebrae; it does not extend the entire length of the vertebral column. It is around 45 cm (18 in) in men and around 43 cm (17 in) long in women. Also, the spinal cord has a varying width, ranging from 1/2 inch thick in the cervical and lumbar regions to 1/4 inch thick in the thoracic area. The enclosing bony vertebral column protects the relatively shorter spinal cord. The spinal cord functions primarily in the transmission of neural signals between the brain and the rest of the body but also contains neural circuits that can independently control numerous reflexes and central pattern generators. The spinal cord has three major functions: A. Serve as a conduit for motor information, which travels down the spinal cord. B. Serve as a conduit for sensory information, which travels up the spinal cord. C. Serve as a center for coordinating certain reflexes.

Structure

The spinal cord is the main pathway for information connecting the brain and peripheral nervous system. The length of the spinal cord is much shorter than the length of the bony spinal column. The human spinal cord extends from the medulla oblongata and continues through the conus medullaris near the first or second lumbar vertebra, terminating in a fibrous extension known as the filum terminale.

It is about 45 cm (18 in) long in men and around 43 cm (17 in) in women, ovoid-shaped, and is enlarged in the cervical and lumbar regions. The cervical enlargement, located from C4 to T1, is where sensory input comes from and motor output goes to the arms. The lumbar enlargement, located between L4 and S3, handles sensory input and motor output coming from and going to the legs.

The spinal cord is protected by three layers of tissue, called spinal meninges, that surround the canal. The dura mater is the outermost layer, and it forms a tough protective coating. Between the dura mater and the surrounding bone of the vertebrae is a space called the epidural space. The epidural space is filled with adipose tissue, and it contains a network of blood vessels. The arachnoid mater is the middle protective layer. Its name comes from the fact that the tissue has a spiderweb-like appearance. The space between the arachnoid and the underlyng pia mater is called the subarachnoid space. The subarachnoid space contains cerebrospinal fluid (CSF). The medical procedure known as a lumbar puncture (or spinal tap) involves use of a needle to withdraw cerebrospinal fluid from the subarachnoid space, usually from the lumbar region of the spine. The pia mater is the innermost protective layer. It is very delicate and it is tightly associated with the surface of the spinal cord. The cord is stabilized within the dura mater by the connecting denticulate ligaments, which extend from the enveloping pia mater laterally between the dorsal and ventral roots. The dural sac ends at the vertebral level of the second sacral vertebra.

In cross-section, the peripheral region of the cord contains neuronal white matter tracts containing sensory and motor neurons. Internal to this peripheral region is the gray, butterfly-shaped central region made up of nerve cell bodies. This central region surrounds the central canal, which is an anatomic extension of the spaces in the brain known as the ventricles and, like the ventricles, contains cerebrospinal fluid.

The spinal cord has a shape that is compressed dorso-ventrally, giving it an elliptical shape. The cord has grooves in the dorsal and ventral sides. The posterior median sulcus is the groove in the dorsal side, and the anterior median fissure is the groove in the ventral side.

Spinal cord segments

The human spinal cord is divided into 31 different segments. At every segment, right and left pairs of spinal nerves (mixed; sensory and motor) form. Six to eight motor nerve rootlets branch out of right and left ventro lateral sulci in a very orderly manner. Nerve rootlets combine to form nerve roots. Likewise, sensory nerve rootlets form off right and left dorsal lateral sulci and form sensory nerve roots. The ventral (motor) and dorsal (sensory) roots combine to form spinal nerves (mixed; motor and sensory), one on each side of the spinal cord. Spinal nerves, with the exception of C1 and C2, form inside intervertebral foramen (IVF). Note that at each spinal segment, the border between the central and peripheral nervous system can be observed. Rootlets are a part of the peripheral nervous system.

In the upper part of the vertebral column, spinal nerves exit directly from the spinal cord, whereas in the lower part of the vertebral column nerves pass further down the column before exiting. The terminal portion of the spinal cord is called the conus medullaris. The pia mater continues as an extension called the filum terminale, which anchors the spinal cord to the coccyx. The cauda equina (“horse’s tail”) is the name for the collection of nerves in the vertebral column that continue to travel through the vertebral column below the conus medullaris. The cauda equina forms as a result of the fact that the spinal cord stops growing in length at about age four, even though the vertebral column continues to lengthen until adulthood. This results in the fact that sacral spinal nerves actually originate in the upper lumbar region. The spinal cord can be anatomically divided into 31 spinal segments based on the origins of the spinal nerves.

Each segment of the spinal cord is associated with a pair of ganglia, called dorsal root ganglia, which are situated just outside of the spinal cord. These ganglia contain cell bodies of sensory neurons. Axons of these sensory neurons travel into the spinal cord via the dorsal roots.

Ventral roots consist of axons from motor neurons, which bring information to the periphery from cell bodies within the CNS. Dorsal roots and ventral roots come together and exit the intervertebral foramina as they become spinal nerves.

The gray matter, in the center of the cord, is shaped like a butterfly and consists of cell bodies of interneurons and motor neurons. It also consists of neuroglia cells and unmyelinated axons. Projections of the gray matter (the “wings”) are called horns. Together, the gray horns and the gray commissure form the “gray H.”

The white matter is located outside of the gray matter and consists almost totally of myelinated motor and sensory axons. “Columns” of white matter carry information either up or down the spinal cord.

Within the CNS, nerve cell bodies are generally organized into functional clusters, called nuclei. Axons within the CNS are grouped into tracts.

There are 33 (some EMS text say 25, counting the sacral as one solid piece) spinal cord nerve segments in a human spinal cord:

• 8 cervical segments forming 8 pairs of cervical nerves (C1 spinal nerves exit spinal column between occiput and C1 vertebra; C2 nerves exit between posterior arch of C1 vertebra and lamina of C2 vertebra; C3-C8 spinal nerves through IVF above corresponding cervica vertebra, with the exception of C8 pair which exit via IVF between C7 and T1 vertebra)
• 12 thoracic segments forming 12 pairs of thoracic nerves (exit spinal column through IVF below corresponding vertebra T1-T12)
• 5 lumbar segments forming 5 pairs of lumbar nerves (exit spinal column through IVF, below corresponding vertebra L1-L5)
• 5 (or 1) sacral segments forming 5 pairs of sacral nerves (exit spinal column through IVF, below corresponding vertebra S1-S5)
• 3 coccygeal segments joined up becoming a single segment forming 1 pair of coccygeal nerves (exit spinal column through the sacral hiatus).

Because the vertebral column grows longer than the spinal cord, spinal cord segments do not correspond to vertebral segments in adults, especially in the lower spinal cord. In the fetus, vertebral segments do correspond with spinal cord segments. In the adult, however, the spinal cord ends around the L1/L2 vertebral level, forming a structure known as the conus medullaris. For example, lumbar and sacral spinal cord segments are found between vertebral levels T9 and L2.

Although the spinal cord cell bodies end around the L1/L2 vertebral level, the spinal nerves for each segment exit at the level of the corresponding vertebra. For the nerves of the lower spinal cord, this means that they exit the vertebral column much lower (more caudally) than their roots. As these nerves travel from their respective roots to their point of exit from the vertebral column, the nerves of the lower spinal segments form a bundle called the cauda equina.

There are two regions where the spinal cord enlarges:

• Cervical enlargement - corresponds roughly to the brachial plexus nerves, which innervate the upper limb. It includes spinal cord segments from about C4 to T1. The vertebral levels of the enlargement are roughly the same (C4 to T1).

• Lumbosacral enlargement - corresponds to the lumbosacral plexus nerves, which innervate the lower limb. It comprises the spinal cord segments from L2 to S3 and is found about the vertebral levels of T9 to T12.

The central nervous system (CNS) is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish. It contains the majority of the nervous system and consists of the brain and the spinal cord. Some classifications also include the retina and the cranial nerves in the CNS. Together with the peripheral nervous system, it has a fundamental role in the control of behavior. The CNS is contained within the dorsal cavity, with the brain in the cranial cavity and the spinal cord in the spinal cavity. In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae, and both are enclosed in the meninges.

Development

Development of the neural tube

During early development of the vertebrate embryo, a longitudinal groove on the neural plate gradually deepens as ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube, the ectodermal wall of which forms the rudiment of the nervous system. This tube initially differentiates into three vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon; and the rhombencephalon divides into the metencephalon and myelencephalon.

As the vertebrate grows, these vesicles differentiate further still. The telencephalon differentiates into, among other things, the striatum, the hippocampus and the neocortex, and its cavity becomes the first and second ventricles. Diencephalon elaborations include the subthalamus, hypothalamus, thalamus and epithalamus, and its cavity forms the third ventricle. The tectum, pretectum, cerebral peduncle and other structures develop out of the mesencephalon, and its cavity grows into the mesencephalic duct (cerebral aqueduct). The metencephalon becomes, among other things, the pons and the cerebellum, the myelencephalon forms the medulla oblongata, and their cavities develop into the fourth ventricle.

Brain regions of a 4 week old human embryo

Evolution

The central nervous system (2) is a combination of the brain (1) and the spinal cord (3).

Planarians, members of the phylum Platyhelminthes (flatworms), have the simplest, clearly defined delineation of a nervous system into a central nervous system (CNS) and a peripheral nervous system (PNS).^{[2] [3]} Their primitive brain, consisting of two fused anterior ganglia, and longitudinal nerve cords form the CNS; the laterally projecting nerves form the PNS. A molecular study found that more than 95% of the 116 genes involved in the nervous system of planarians, which includes genes related to the CNS, also exist in humans.^[4] Like planarians, vertebrates have a distinct CNS and PNS, though more complex than those of planarians.

The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: the telencephalon of reptiles is only an appendix to the large olfactory bulb, while in mammals it makes up most of the volume of the CNS. In the human brain, the telencephalon covers most of the diencephalon and the mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

Mammals – which appear in the fossil record after the first fishes, amphibians, and reptiles – are the only vertebrates to possess the evolutionarily recent, outermost part of the cerebral cortex known as the neocortex.^[5] The neocortex of monotremes (the duck-billed platypus and several species of spiny anteaters) and of marsupials (such as kangaroos, koalas, opossums, wombats, and Tasmanian devils) lack the convolutions – gyri and sulci – found in the neocortex of most placental mammals (eutherians).^[6] Within placental mammals, the size and complexity of the neocortex increased over time. The area of the neocortex of mice is only about 1/100 that of monkeys, and that of monkeys is only about 1/10 that of humans.^[5] In addition, rats lack convolutions in their neocortex (possibly also because rats are small mammals), whereas cats have a moderate degree of convolutions, and humans have quite extensive convolutions.^[5]

Diseases of the central nervous system

There are many central nervous system diseases, including infections of the central nervous system such as encephalitis and poliomyelitis, neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis, autoimmune and inflammatory diseases such as multiple sclerosis or acute disseminated encephalomyelitis, and genetic disorders such as Krabbe's disease, Huntington's disease, or adrenoleukodystrophy. Lastly, cancers of the central nervous system can cause severe illness and, when malignant, can have very high mortality rates. 

The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous system of vertebrates (such as humans) contains the brain, spinal cord, and retina. The peripheral nervous system consists of sensory neurons, clusters of neurons called ganglia, and nerves connecting them to each other and to the central nervous system. These regions are all interconnected by means of complex neural pathways. The enteric nervous system, a subsystem of the peripheral nervous system, has the capacity, even when severed from the rest of the nervous system through its primary connection by the vagus nerve, to function independently in controlling the gastrointestinal system.

Neurons send signals to other cells as electrochemical waves travelling along thin fibers called axons, which cause chemicals called neurotransmitters to be released at junctions called synapses. A cell that receives a synaptic signal may be excited, inhibited, or otherwise modulated. Sensory neurons are activated by physical stimuli impinging on them, and send signals that inform the central nervous system of the state of the body and the external environment. Motor neurons, situated either in the central nervous system or in peripheral ganglia, connect the nervous system to muscles or other effector organs. Central neurons, which in vertebrates greatly outnumber the other types, make all of their input and output connections with other neurons. The interactions of all these types of neurons form neural circuits that generate an organism's perception of the world and determine its behavior. Along with neurons, the nervous system contains other specialized cells called glial cells (or simply glia), which provide structural and metabolic support.

Nervous systems are found in most multicellular animals, but vary greatly in complexity.^[1] Sponges have no nervous system, although they have homologs of many genes that play crucial roles in nervous system function, and are capable of several whole-body responses, including a primitive form of locomotion. Placozoans and mesozoans—other simple animals that are not classified as part of the subkingdom Eumetazoa—also have no nervous system. In Radiata (radially symmetric animals such as jellyfish) the nervous system consists of a simple nerve net. Bilateria, which include the great majority of vertebrates and invertebrates, all have a nervous system containing a brain, one central cord (or two running in parallel), and peripheral nerves. The size of the bilaterian nervous system ranges from a few hundred cells in the simplest worms, to on the order of 100 billion cells in humans. Neuroscience is the study of the nervous system.

Structure

The nervous system derives its name from nerves, which are cylindrical bundles of fibers that emanate from the brain and central cord, and branch repeatedly to innervate every part of the body.^[2] Nerves are large enough to have been recognized by the ancient Egyptians, Greeks, and Romans,^[3] but their internal structure was not understood until it became possible to examine them using a microscope.^[4] A microscopic examination shows that nerves consist primarily of the axons of neurons, along with a variety of membranes that wrap around them and segregate them into fascicles. The neurons that give rise to nerves do not lie entirely within the nerves themselves—their cell bodies reside within the brain, central cord, or peripheral ganglia.^[2]

All animals more advanced than sponges have nervous systems. However, even sponges, unicellular animals, and non-animals such as slime molds have cell-to-cell signalling mechanisms that are precursors to those of neurons.^[5] In radially symmetric animals such as the jellyfish and hydra, the nervous system consists of a diffuse network of isolated cells.^[6] In bilaterian animals, which make up the great majority of existing species, the nervous system has a common structure that originated early in the Cambrian period, over 500 million years ago.^[7]

Cells

The nervous system is primarily made up of two categories of cells: neurons and glial cells.

Neurons

Structure of a typical neuron

Neuron
Dendrite Soma Axon Nucleus Node of Ranvier Axon terminal Schwann cell Myelin sheath

The nervous system is defined by the presence of a special type of cell—the neuron (sometimes called "neurone" or "nerve cell").^[2] Neurons can be distinguished from other cells in a number of ways, but their most fundamental property is that they communicate with other cells via synapses, which are membrane-to-membrane junctions containing molecular machinery that allows rapid transmission of signals, either electrical or chemical.^[2] Many types of neuron possess an axon, a protoplasmic protrusion that can extend to distant parts of the body and make thousands of synaptic contacts.^[8] Axons frequently travel through the body in bundles called nerves.

Even in the nervous system of a single species such as humans, hundreds of different types of neurons exist, with a wide variety of morphologies and functions.^[8] These include sensory neurons that transmute physical stimuli such as light and sound into neural signals, and motor neurons that transmute neural signals into activation of muscles or glands; however in many species the great majority of neurons receive all of their input from other neurons and send their output to other neurons.^[2]

Glial cells

Glial cells are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system.^[9] In the human brain, it is estimated that the total number of glia roughly equals the number of neurons, although the proportions vary in different brain areas.^[10] Among the most important functions of glial cells are to support neurons and hold them in place; to supply nutrients to neurons; to insulate neurons electrically; to destroy pathogens and remove dead neurons; and to provide guidance cues directing the axons of neurons to their targets.^[9] A very important type of glial cell (oligodendrocytes in the central nervous system, and Schwann cells in the peripheral nervous system) generates layers of a fatty substance called myelin that wraps around axons and provides electrical insulation which allows them to transmit action potentials much more rapidly and efficiently. 

A biological membrane or biomembrane is an enclosing or separating membrane that acts as a selective barrier, within or around a cell. It consist of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content.^[1] The cellular membranes should not be confused with isolating tissues formed by layers of cells, such as mucous and basement membranes.

Function

Membranes in cells typically define enclosed spaces or compartments in which cells may maintain a chemical or biochemical environment that differs from the outside. For example, the membrane around peroxisomes shields the rest of the cell from peroxides, and the cell membrane separates a cell from its surrounding medium. Most organelles are defined by such membranes, and are called "membrane-bound" organelles.

Probably the most important feature of a biomembrane is that it is a selectively permeable structure. This means that the size, charge, and other chemical properties of the atoms and molecules attempting to cross it will determine whether they succeed in doing so. Selective permeability is essential for effective separation of a cell or organelle from its surroundings. Biological membranes also have certain mechanical or elastic properties.

Particles that are required for cellular function but are unable to diffuse freely across a membrane enter through a membrane transport protein or are taken in by means of endocytosis.

Diversity of biological membranes

Many types of specialized plasma membranes can separate cell from external environment: apical, basolateral, presynaptic and postsynaptic ones, membranes of flagella, cilia, microvillus, filopodia and lamellipodia, the sarcolemma of muscle cells, as well as specialized myelin and dendritic spine membranes of neurons. Plasma membranes can also form different types of "supramembrane" structures such as caveola, postsynaptic density, podosome, invadopodium, desmosome, hemidesmosome, focal adhesion, and cell junctions. These types of membranes differ in lipid and protein composition.

Distinct types of membranes also create intracellular organelles: endosome; smooth and rough endoplasmic reticulum ; sarcoplasmic reticulum; Golgi apparatus; lysosome; mitochondrion (inner and outer membranes); nucleus (inner and outer membranes); peroxisome; vacuole; cytoplasmic granules; cell vesicles (phagosome, autophagosome, clathrin-coated vesicles, COPI-coated and COPII-coated vesicles) and secretory vesicles (including synaptosome, acrosomes, melanosomes, and chromaffin granules).

Different types of biological membranes have diverse lipid and protein compositions. The content of membranes defines their physical and biological properties. Some components of membranes play a key role in medicine, such as the efflux pumps that pump drugs out of a cell. 

Transpiration is a process similar to evaporation. It is a part of the water cycle, and it is the loss of water vapor from parts of plants (similar to sweating), especially in leaves but also in stems, flowers and roots. Leaf surfaces are dotted with openings which are collectively called stomata, and in most plants they are more numerous on the undersides of the foliage. The stoma are bordered by guard cells that open and close the pore. ^[1] Leaf transpiration occurs through stomata, and can be thought of as a necessary "cost" associated with the opening of the stomata to allow the diffusion of carbon dioxide gas from the air for photosynthesis. Transpiration also cools plants and enables mass flow of mineral nutrients and water from roots to shoots.

Mass flow of liquid water from the roots to the leaves is caused by the decrease in hydrostatic (water) pressure in the upper parts of the plants due to the diffusion of water out of stomata into the atmosphere. Water is absorbed at the roots by osmosis, and any dissolved mineral nutrients travel with it through the xylem.

The rate of transpiration is directly related to the evaporation of water molecules from plant surface, especially from the surface openings, or stoma, on leaves. Stomatal transpiration accounts for most of the water loss by a plant, but some direct evaporation also takes place through the cuticle of the leaves and young stems. The amount of water given off depends somewhat upon how much water the roots of the plant have absorbed. It also depends upon such environmental conditions as light intensity, humidity, winds and temperature. A plant should not be transplanted in full sunshine because it may lose too much water and wilt before the damaged roots can supply enough water. Transpiration occurs as the sun warms the water inside the blade. The warming changes much of the water into water vapour. This gas can then escape through the stomata. Transpiration helps cool the inside of the leaf because the escaping vapor has absorbed heat, the degree of stomatal opening, and the evaporative demand of the atmosphere surrounding the leaf. The amount of water lost by a plant depends on its size, along with surrounding light intensity,^[2] temperature, humidity, and wind speed (all of which influence evaporative demand). Soil water supply and soil temperature can influence stomatal opening, and thus transpiration rate.

A fully grown tree may lose several hundred gallons of water through its leaves on a hot, dry day. About 90% of the water that enters a plant's roots is used for this process. The transpiration ratio is the ratio of the mass of water transpired to the mass of dry matter produced; the transpiration ratio of crops tends to fall between 200 and 1000 (i.e., crop plants transpire 200 to 1000 kg of water for every kg of dry matter produced).^[3]

Transpiration rate of plants can be measured by a number of techniques, including potometers, lysimeters, porometers, photosynthesis systems and heat balance sap flow gauges.

Desert plants and conifers have specially adapted structures, such as thick cuticles, reduced leaf areas, sunken stomata and hairs to reduce transpiration and conserve water. Many cacti conduct photosynthesis in succulent stems, rather than leaves, so the surface area of the shoot is very low. Many desert plants have a special type of photosynthesis, termed crassulacean acid metabolism or CAM photosynthesis in which the stomata are closed during the day and open at night when transpiration will be lower.

A eukaryote (pronounced /juːˈkæri.oʊt/ ew-KARR-ee-oht or /juːˈkæriət/) is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried.^[1][2][3] The presence of a nucleus gives eukaryotes their name, which comes from the Greek ευ (eu, "good") and κάρυον (karyon, "nut" or "kernel"). Most eukaryotic cells also contain other membrane-bound organelles such as mitochondria, chloroplasts and the Golgi apparatus. All species of large complex organisms are eukaryotes, including animals, plants and fungi, although most species of eukaryotic protists are microorganisms.

Cell division in eukaryotes is different from that in organisms without a nucleus (prokaryotes). It involves separating the duplicated chromosomes, through movements directed by microtubules. There are two types of division processes. In mitosis, one cell divides to produce two genetically identical cells. In meiosis, which is required in sexual reproduction, one diploid cell (having two instances of each chromosome, one from each parent) undergoes recombination of each pair of parental chromosomes, and then two stages of cell division, resulting in four haploid cells (gametes). Each gamete has just one complement of chromosomes, each a unique mix of the corresponding pair of parental chromosomes.

Eukaryotes appear to be monophyletic, and so make up one of the three domains of life. The two other domains, Bacteria and Archaea, are prokaryotes and have none of the above features. Eukaryotes represent a tiny minority of all living things; even in a human body there are 10 times more microbes than human cells.

Chloroplasts (English pronunciation: /ˈklɒrəplæsts/) are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.^[1]

Chloroplasts are green because they contain the pigment chlorophyll. The word chloroplast (χλωροπλάστης) is derived from the Greek words chloros (χλωρός), which means green, and plastis (πλάστης), which means "the one who forms". Chloroplasts are members of a class of organelles known as plastids.

Chloroplasts are one of the many different types of organelles in the plant cell. In general, they are considered to have originated from cyanobacteria through endosymbiosis. This was first suggested by Mereschkowsky in 1905^[2] after an observation by Schimper in 1883 that chloroplasts closely resemble cyanobacteria.^[3] All chloroplasts are thought to derive directly or indirectly from a single endosymbiotic event (in the Archaeplastida), except for Paulinella chromatophora, which has recently acquired a photosynthetic cyanobacterial endosymbiont which is not closely related to chloroplasts of other eukaryotes.^[4] In that they derive from an endosymbiotic event, chloroplasts are similar to mitochondria, but chloroplasts are found only in plants and protista. The chloroplast is surrounded by a double-layered composite membrane with an intermembrane space; further, it has reticulations, or many infoldings, filling the inner spaces. The chloroplast has its own DNA,^[5] which codes for redox proteins involved in electron transport in photosynthesis; this is termed the plastome.^[6]

In green plants, chloroplasts are surrounded by two lipid-bilayer membranes. They are believed to correspond to the outer and inner membranes of the ancestral cyanobacterium.^[7] Chloroplasts have their own genome, which is considerably reduced compared to that of free-living cyanobacteria, but the parts that are still present show clear similarities with the cyanobacterial genome. Plastids may contain 60-100 genes whereas cyanobacteria often contain more than 1500 genes.^[8] Many of the missing genes are encoded in the nuclear genome of the host. The transfer of nuclear information has been estimated in tobacco plants at one gene for every 16000 pollen grains.^[9]

In some algae (such as the heterokonts and other protists such as Euglenozoa and Cercozoa), chloroplasts seem to have evolved through a secondary event of endosymbiosis, in which a eukaryotic cell engulfed a second eukaryotic cell containing chloroplasts, forming chloroplasts with three or four membrane layers. In some cases, such secondary endosymbionts may have themselves been engulfed by still other eukaryotes, thus forming tertiary endosymbionts. In the alga Chlorella, there is only one chloroplast, which is bell-shaped.

In some groups of mixotrophic protists such as the dinoflagellates, chloroplasts are separated from a captured alga or diatom and used temporarily. These klepto chloroplasts may only have a lifetime of a few days and are then replaced.^[10]

Structure

Chloroplasts are observable as flat discs usually 2 to 10 micrometers in diameter and 1 micrometer thick. In land plants, they are, in general, 5 μm in diameter and 2.3 μm thick. The chloroplast is contained by an envelope that consists of an inner and an outer phospholipid membrane. Between these two layers is the intermembrane space. A typical parenchyma cell contains about 10 to 100 chloroplasts.

Chloroplast ultrastructure:
1. outer membrane
2. intermembrane space
3. inner membrane (1+2+3: envelope)
4. stroma (aqueous fluid)
5. thylakoid lumen (inside of thylakoid)
6. thylakoid membrane
7. granum (stack of thylakoids)
8. thylakoid (lamella)
9. starch
10. ribosome
11. plastidial DNA
12. plastoglobule (drop of lipids)

The material within the chloroplast is called the stroma, corresponding to the cytosol of the original bacterium, and contains one or more molecules of small circular DNA. It also contains ribosomes; however most of its proteins are encoded by genes contained in the host cell nucleus, with the protein products transported to the chloroplast.

TEM image of a chloroplast

Within the stroma are stacks of thylakoids, the sub-organelles, which are the site of photosynthesis. The thylakoids are arranged in stacks called grana (singular: granum).^[1] A thylakoid has a flattened disk shape. Inside it is an empty area called the thylakoid space or lumen. Photosynthesis takes place on the thylakoid membrane; as in mitochondrial oxidative phosphorylation, it involves the coupling of cross-membrane fluxes with biosynthesis via the dissipation of a proton electrochemical gradient.

In the electron microscope, thylakoid membranes appear as alternating light-and-dark bands, each 0.01 μm thick. Embedded in the thylakoid membrane are antenna complexes, each of which consists of the light-absorbing pigments, including chlorophyll and carotenoids, as well as proteins that bind the pigments. This complex both increases the surface area for light capture, and allows capture of photons with a wider range of wavelengths. The energy of the incident photons is absorbed by the pigments and funneled to the reaction centre of this complex through resonance energy transfer. Two chlorophyll molecules are then ionised, producing an excited electron, which then passes onto the photochemical reaction centre.

Recent studies have shown that chloroplasts can be interconnected by tubular bridges called stromules, formed as extensions of their outer membranes.^[11][12] Chloroplasts appear to be able to exchange proteins via stromules,^[13] and thus function as a network.

Transplastomic plants

Recently, chloroplasts have caught attention by developers of genetically modified plants. In most flowering plants, chloroplasts are not inherited from the male parent,^[14][15] although in plants such as pines, chloroplasts are inherited from males.^[16] Where chloroplasts are inherited only from the female, transgenes in these plastids cannot be disseminated by pollen. This makes plastid transformation a valuable tool for the creation and cultivation of genetically modified plants that are biologically contained, thus posing significantly lower environmental risks. This biological containment strategy is therefore suitable for establishing the coexistence of conventional and organic agriculture. While the reliability of this mechanism has not yet been studied for all relevant crop species, recent results in tobacco plants are promising, showing a failed containment rate of transplastomic plants at 3 in 1,000,000.^[ 

In botany, a leaf is an above-ground plant organ specialized for the process of photosynthesis. Leaves are typically flat (laminar) and thin which evolved as a means to maximise the surface area directly exposed to light. Furthermore the internal organisation of leaves has evolved to maximise exposure of the photosynthetic organelles, the chloroplasts, to light and to increase the absorption of carbon dioxide, all of which assist photosynthesis. These adaptations are at the expense of water loss and most leaves have stomata which regulate carbon dioxide, oxygen and water vapour exchange with the atmosphere. The shape and structure of leaves varies considerably depending on climate, primarily due to the availability of light and potential for water loss due to temperature and humidity. Leaves are also the primary site, in most plants, where transpiration and guttation take place. Leaves can also store food and water, and are modified in some plants for these purposes. The concentration of photosynthesis in leaves makes them rich in protein, minerals and sugars. Because of their nutritional value leaves are prominent in the diet of many animals, including humans as leaf vegetables.

A leaf shed in autumn.

Many plants retain their leaves for long periods however notably some plants periodically (seasonally, during the autumn) shed their leaves. This behavior is prevalent at temperate latitudes where deciduous trees shed their leaves which would otherwise damaged by freezing temperatures during winter. The shed leaves then decompose into the soil and the trees regrow their leaves during spring.

Not all plants have true leaves. Bryophytes (i.e. mosses and liverworts) are non-vascular plants, and although they have flattened, leaf-like structures that are rich in chlorophyll, these are not considered true leaves by all botanists since they lack vascular tissue. Vascularised leaves first evolved following the Devonian period, when carbon dioxide concentration in the atmosphere dropped significantly. This occurred independently in two separate lineages of vascular plants: the microphylls of lycophytes and the euphylls ("true leaves") of ferns, gymnosperms, and angiosperms. Euphylls are also referred to as macrophylls or megaphylls ("large leaves").

Anatomy

Large scale features

A structurally complete leaf of an angiosperm consists of a petiole (leaf stalk), a lamina (leaf blade), and stipules (small structures located to either side of the base of the petiole). The petiole attaches to the stem at a point called the leaf axil. Not every species produces leaves with all of these structural components. In certain species, paired stipules are not obvious or are absent altogether. A petiole may be absent, or the blade may not be laminar (flattened). The tremendous variety shown in leaf structure (anatomy) from species to species is presented in detail below under Leaf morphology.

The petiole mechanically links the leaf to the plant and provides the route for transfer of water and sugars to and from the leaf. The lamina is typically the location of the majority of photosynthesis.

Medium scale features

Leaves are normally extensively vascularised and are typically covered by a dense network of xylem, which supply water for photosynthesis, and phloem, which remove the sugars produced by photosynthesis. Many leaves are covered in trichromes (small hairs) which have a diverse range of structures and functions.

Small scale features

A leaf is a plant organ and is made up of a collection of tissues in a regular organisation. The major tissue systems present are:

1. The epidermis that covers the upper and lower surfaces
2. The mesophyll inside the leaf that is rich in chloroplasts (also called chlorenchyma)
3. The arrangement of veins (the vascular tissue)

These three tissue systems typically form a regular organisation at the cellular scale.

Major leaf tissues

Epidermis

SEM image of Nicotiana alata leaf's epidermis, showing trichomes (hair-like appendages) and stomata (eye-shaped slits, visible at full resolution).

The epidermis is the outer layer of cells covering the leaf. It forms the boundary separating the plant's inner cells from the external world. The epidermis serves several functions: protection against water loss by way of transpiration, regulation of gas exchange, secretion of metabolic compounds, and (in some species) absorption of water. Most leaves show dorsoventral anatomy: the upper (adaxial) and lower (abaxial) surfaces have somewhat different construction and may serve different functions.

The epidermis is usually transparent (epidermal cells lack chloroplasts) and coated on the outer side with a waxy cuticle that prevents water loss. The cuticle is in some cases thinner on the lower epidermis than on the upper epidermis, and is generally thicker on leaves from dry climates as compared with those from wet climates.

The epidermis tissue includes several differentiated cell types: epidermal cells, epidermal hair cells (trichomes) cells in the stomate complex; guard cells and subsidiary cells. The epidermal cells are the most numerous, largest, and least specialized and form the majority of the epidermis. These are typically more elongated in the leaves of monocots than in those of dicots.

The epidermis is covered with pores called stomata, part of a stoma complex consisting of a pore surrounded on each side by chloroplast-containing guard cells, and two to four subsidiary cells that lack chloroplasts. By opening and closing the stoma complex regulates the exchange of gases and water vapor between the outside air and the interior of the leaf and plays an important role in allowing photosynthesis without letting the leaf dry out. Typically, the stomata are more numerous over the abaxial (lower) epidermis than the adaxial (upper) epidermis and more numerous in plants from cooler climates.

Mesophyll

Most of the interior of the leaf between the upper and lower layers of epidermis is a parenchyma (ground tissue) or chlorenchyma tissue called the mesophyll (Greek for "middle leaf"). This assimilation tissue is the primary location of photosynthesis in the plant. The products of photosynthesis are called "assimilates".

In ferns and most flowering plants the mesophyll is divided into two layers:

• An upper palisade layer of tightly packed, vertically elongated cells, one to two cells thick, directly beneath the adaxial epidermis. Its cells contain many more chloroplasts than the spongy layer. These long cylindrical cells are regularly arranged in one to five rows. Cylindrical cells, with the chloroplasts close to the walls of the cell, can take optimal advantage of light. The slight separation of the cells provides maximum absorption of carbon dioxide. This separation must be minimal to afford capillary action for water distribution. In order to adapt to their different environment (such as sun or shade), plants had to adapt this structure to obtain optimal result. Sun leaves have a multi-layered palisade layer, while shade leaves or older leaves closer to the soil, are single-layered.
• Beneath the palisade layer is the spongy layer. The cells of the spongy layer are more rounded and not so tightly packed. There are large intercellular air spaces. These cells contain fewer chloroplasts than those of the palisade layer. The pores or stomata of the epidermis open into substomatal chambers which are connected to the air spaces between the spongy layer cells.

These two different layers of the mesophyll are absent in many aquatic and marsh plants. Even an epidermis and a mesophyll may be lacking. Instead for their gaseous exchanges they use a homogeneous aerenchyma (thin-walled cells separated by large gas-filled spaces). Their stomata are situated at the upper surface.

Leaves are normally green in color, which comes from chlorophyll found in plastids in the chlorenchyma cells. Plants that lack chlorophyll cannot photosynthesize.

Veins

The veins of a bramble leaf.

The veins are the vascular tissue of the leaf and are located in the spongy layer of the mesophyll. They are typical examples of pattern formation through ramification. The pattern of the veins is called venation.

The veins are made up of:

• Xylem: tubes that brings water and minerals from the roots into the leaf.
• Phloem: tubes that usually move sap, with dissolved sucrose, produced by photosynthesis in the leaf, out of the leaf.

The xylem typically lie on the adaxial side of the vascular bungle and the phloem typically lie on the abaxial side. Both are embedded in a dense parenchyma tissue, called the pith or sheath, which usually includes some structural collenchyma tissue.

Seasonal leaf loss

Leaves shifting color in fall

Leaves in temperate, boreal, and seasonally dry zones may be seasonally deciduous (falling off or dying for the inclement season). This mechanism to shed leaves is called abscission. After the leaf is shed, a leaf scar develops on the twig. In cold autumns they sometimes change color, and turn yellow, bright orange or red as various accessory pigments (carotenoids and xanthophylls) are revealed when the tree responds to cold and reduced sunlight by curtailing chlorophyll production. Red anthocyanin pigments are now thought to be produced in the leaf as it dies, possibly to mask the yellow hue left when the chlorophyll is lost - yellow leaves appear to attract herbivores such as aphids.^[1]

Morphology

The Citrus leaf is identified by the pores and pigments, as well as the margins.

External leaf characteristics (such as shape, margin, hairs, etc.) are important for identifying plant species, and botanists have developed a rich terminology for describing leaf characteristics. These structures are a part of what makes leaves determinant; they grow and achieve a specific pattern and shape, then stop. Other plant parts like stems or roots are non-determinant, and will usually continue to grow as long as they have the resources to do so.

Classification of leaves can occur through many different designative schema, and the type of leaf is usually characteristic of a species, although some species produce more than one type of leaf. The longest type of leaf is a leaf from palm trees, measuring at nine feet long. The terminology associated with the description of leaf morphology is presented, in illustrated form, at Wikibooks.

Basic types

Leaves of the White Spruce (Picea glauca) are needle-shaped and their arrangement is spiral

• Ferns have fronds
• Conifer leaves are typically needle-, awl-, or scale-shaped
• Angiosperm (flowering plant) leaves: the standard form includes stipules, a petiole, and a lamina
• Lycophytes have microphyll leaves.
• Sheath leaves (type found in most grasses)
• Other specialized leaves (such as those of Nepenthes)

Arrangement on the stem

Different terms are usually used to describe leaf placement (phyllotaxis):

The leaves on this plant are arranged in pairs opposite one another, with successive pairs at right angles to each other ("decussate") along the red stem. Note developing buds in the axils of these leaves.

• Alternate — leaf attachments are singular at nodes, and leaves alternate direction, to a greater or lesser degree, along the stem.
• Opposite — Two structures, one on each opposite side of the stem, typically leaves, branches, or flower parts. Leaf attachments are paired at each node; decussate if, as typical, each successive pair is rotated 90° progressing along the stem; or distichous if not rotated, but two-ranked (in the same geometric flat-plane).
• Whorled — three or more leaves attach at each point or node on the stem. As with opposite leaves, successive whorls may or may not be decussate, rotated by half the angle between the leaves in the whorl (i.e., successive whorls of three rotated 60°, whorls of four rotated 45°, etc.). Opposite leaves may appear whorled near the tip of the stem.
• Rosulate — leaves form a rosette

As a stem grows, leaves tend to appear arranged around the stem in a way that optimizes yield of light. In essence, leaves form a helix pattern centred around the stem, either clockwise or counterclockwise, with (depending upon the species) the same angle of divergence. There is a regularity in these angles and they follow the numbers in a Fibonacci sequence: 1/2, 2/3, 3/5, 5/8, 8/13, 13/21, 21/34, 34/55, 55/89. This series tends to a limit close to 360° x 34/89 = 137.52 or 137° 30', an angle known mathematically as the golden angle. In the series, the numerator indicates the number of complete turns or "gyres" until a leaf arrives at the initial position. The denominator indicates the number of leaves in the arrangement. This can be demonstrated by the following:

• alternate leaves have an angle of 180° (or 1/2)
• 120° (or 1/3) : three leaves in one circle
• 144° (or 2/5) : five leaves in two gyres
• 135° (or 3/8) : eight leaves in three gyres.

Divisions of the blade

A leaf with laminar structure and pinnate venation

Two basic forms of leaves can be described considering the way the blade (lamina) is divided. A simple leaf has an undivided blade. However, the leaf shape may be formed of lobes, but the gaps between lobes do not reach to the main vein. A compound leaf has a fully subdivided blade, each leaflet of the blade separated along a main or secondary vein. Because each leaflet can appear to be a simple leaf, it is important to recognize where the petiole occurs to identify a compound leaf. Compound leaves are a characteristic of some families of higher plants, such as the Fabaceae. The middle vein of a compound leaf or a frond, when it is present, is called a rachis.

• Palmately compound leaves have the leaflets radiating from the end of the petiole, like fingers off the palm of a hand, e.g. Cannabis (hemp) and Aesculus (buckeyes).
• Pinnately compound leaves have the leaflets arranged along the main or mid-vein.
  • odd pinnate: with a terminal leaflet, e.g. Fraxinus (ash).
  • even pinnate: lacking a terminal leaflet, e.g. Swietenia (mahogany).
• Bipinnately compound leaves are twice divided: the leaflets are arranged along a secondary vein that is one of several branching off the rachis. Each leaflet is called a "pinnule". The pinnules on one secondary vein are called "pinna"; e.g. Albizia (silk tree).
• trifoliate (or trifoliolate): a pinnate leaf with just three leaflets, e.g. Trifolium (clover), Laburnum (laburnum).
• pinnatifid: pinnately dissected to the central vein, but with the leaflets not entirely separate, e.g. Polypodium, some Sorbus (whitebeams). In pinnately veined leaves the central vein in known as the midrib.

Characteristics of the petiole

The overgrown petioles of Rhubarb (Rheum rhabarbarum) are edible.

Petiolated leaves have a petiole (leaf stem). Sessile leaves do not: the blade attaches directly to the stem. In clasping or decurrent leaves, the blade partially or wholly surrounds the stem, often giving the impression that the shoot grows through the leaf. When this is actually the case, the leaves are called "perfoliate", such as in Claytonia perfoliata. In peltate leaves, the petiole attaches to the blade inside from the blade margin.

In some Acacia species, such as the Koa Tree (Acacia koa), the petioles are expanded or broadened and function like leaf blades; these are called phyllodes. There may or may not be normal pinnate leaves at the tip of the phyllode.

A stipule, present on the leaves of many dicotyledons, is an appendage on each side at the base of the petiole resembling a small leaf. Stipules may be lasting and not be shed (a stipulate leaf, such as in roses and beans), or be shed as the leaf expands, leaving a stipule scar on the twig (an exstipulate leaf).

• The situation, arrangement, and structure of the stipules is called the "stipulation".
  • free
  • adnate : fused to the petiole base
  • ochreate : provided with ochrea, or sheath-formed stipules, e.g. rhubarb,
  • encircling the petiole base
  • interpetiolar : between the petioles of two opposite leaves.
  • intrapetiolar : between the petiole and the subtending stem

Venation

Branching veins on underside of taro leaf

The venation within the bract of a Lime tree.

The lower epidermis of Tilia x europea

Palmate-veined leaf

There are two subtypes of venation, namely, craspedodromous, where the major veins stretch up to the margin of the leaf, and camptodromous, when major veins extend close to the margin, but bend before they intersect with the margin.

• Feather-veined, reticulate (also called pinnate-netted, penniribbed, penninerved, or penniveined) — the veins arise pinnately from a single mid-vein and subdivide into veinlets. These, in turn, form a complicated network. This type of venation is typical for (but by no means limited to) dicotyledons.
• Three main veins branch at the base of the lamina and run essentially parallel subsequently, as in Ceanothus. A similar pattern (with 3-7 veins) is especially conspicuous in Melastomataceae.
• Palmate-netted, palmate-veined, fan-veined; several main veins diverge from near the leaf base where the petiole attaches, and radiate toward the edge of the leaf; e.g. most Acer (maples).
• Parallel-veined, parallel-ribbed, parallel-nerved, penniparallel — veins run parallel for the length of the leaf, from the base to the apex. Commissural veins (small veins) connect the major parallel veins. Typical for most monocotyledons, such as grasses.
• Dichotomous — There are no dominant bundles, with the veins forking regularly by pairs; found in Ginkgo and some pteridophytes.

Note that although it is the more complex pattern, branching veins appear to be plesiomorphic and in some form were present in ancient seed plants as long as 250 million years ago. A pseudo-reticulate venation that is actually a highly modified penniparallel one is an autapomorphy of some Melanthiaceae which are monocots, e.g. Paris quadrifolia (True-lover's Knot).

Morphology changes within a single plant

• Homoblasty - Characteristic in which a plant has small changes in leaf size, shape, and growth habit between juvenile and adult stages.
• Heteroblasty - Characteristic in which a plant has marked changes in leaf size, shape, and growth habit between juvenile and adult stages.

Terminology

Chart illustrating some leaf morphology terms

A portion of a celery leaf

Shape

Edge (margin)

• ciliate: fringed with hairs
• crenate: wavy-toothed; dentate with rounded teeth, such as Fagus (beech)
• crenulate finely or shallowly crenate
• dentate: toothed, such as Castanea (chestnut)
  • coarse-toothed: with large teeth
  • glandular toothed: with teeth that bear glands.
• denticulate: finely toothed
• doubly toothed: each tooth bearing smaller teeth, such as Ulmus (elm)
• entire: even; with a smooth margin; without toothing
• lobate: indented, with the indentations not reaching to the center, such as many Quercus (oaks)
  • palmately lobed: indented with the indentations reaching to the center, such as Humulus (hop).
• serrate: saw-toothed with asymmetrical teeth pointing forward, such as Urtica (nettle)
• serrulate: finely serrate
• sinuate: with deep, wave-like indentations; coarsely crenate, such as many Rumex (docks)
• spiny or pungent: with stiff, sharp points, such as some Ilex (hollies) and Cirsium (thistles).

Tip

Leaves showing various morphologies. Clockwise from upper left: tripartite lobation, elliptic with serrulate margin, peltate with palmate venation, acuminate odd-pinnate (center), pinnatisect, lobed, elliptic with entire margin

• acuminate: long-pointed, prolonged into a narrow, tapering point in a concave manner.
• acute: ending in a sharp, but not prolonged point
• cuspidate: with a sharp, elongated, rigid tip; tipped with a cusp.
• emarginate: indented, with a shallow notch at the tip.
• mucronate: abruptly tipped with a small short point, as a continuation of the midrib; tipped with a mucro.
• mucronulate: mucronate, but with a smaller spine.
• obcordate: inversely heart-shaped, deeply notched at the top.
• obtuse: rounded or blunt
• truncate: ending abruptly with a flat end, that looks cut off.

Base

• acuminate: coming to a sharp, narrow, prolonged point.
• acute: coming to a sharp, but not prolonged point.
• auriculate: ear-shaped.
• cordate: heart-shaped with the notch towards the stalk.
• cuneate: wedge-shaped.
• hastate: shaped like an halberd and with the basal lobes pointing outward.
• oblique: slanting.
• reniform: kidney-shaped but rounder and broader than long.
• rounded: curving shape.
• sagittate: shaped like an arrowhead and with the acute basal lobes pointing downward.
• truncate: ending abruptly with a flat end, that looks cut off.

Surface

Scale-shaped leaves of a Norfolk Island Pine, Araucaria heterophylla.

• farinose: bearing farina; mealy, covered with a waxy, whitish powder.
• glabrous: smooth, not hairy.
• glaucous: with a whitish bloom; covered with a very fine, bluish-white powder.
• glutinous: sticky, viscid.
• papillate, or papillose: bearing papillae (minute, nipple-shaped protuberances).
• pubescent: covered with erect hairs (especially soft and short ones).
• punctate: marked with dots; dotted with depressions or with translucent glands or colored dots.
• rugose: deeply wrinkled; with veins clearly visible.
• scurfy: covered with tiny, broad scalelike particles.
• tuberculate: covered with tubercles; covered with warty prominences.
• verrucose: warted, with warty outgrowths.
• viscid, or viscous: covered with thick, sticky secretions.

The leaf surface is also host to a large variety of microorganisms; in this context it is referred to as the phyllosphere.

The parallel veins within an iris leaf.

Hairiness

Common Mullein (Verbascum thapsus) leaves are covered in dense, stellate trichomes.

Scanning electron microscope image of trichomes on the lower surface of a Coleus blumei (coleus) leaf.

"Hairs" on plants are properly called trichomes. Leaves can show several degrees of hairiness. The meaning of several of the following terms can overlap.

• arachnoid, or arachnose: with many fine, entangled hairs giving a cobwebby appearance.
• barbellate: with finely barbed hairs (barbellae).
• bearded: with long, stiff hairs.
• bristly: with stiff hair-like prickles.
• canescent: hoary with dense grayish-white pubescence.
• ciliate: marginally fringed with short hairs (cilia).
• ciliolate: minutely ciliate.
• floccose: with flocks of soft, woolly hairs, which tend to rub off.
• glabrous: no hairs of any kind present.
• glandular: with a gland at the tip of the hair.
• hirsute: with rather rough or stiff hairs.
• hispid: with rigid, bristly hairs.
• hispidulous: minutely hispid.
• hoary: with a fine, close grayish-white pubescence.
• lanate, or lanose: with woolly hairs.
• pilose: with soft, clearly separated hairs.
• puberulent, or puberulous: with fine, minute hairs.
• pubescent: with soft, short and erect hairs.
• scabrous, or scabrid: rough to the touch.
• sericeous: silky appearance through fine, straight and appressed (lying close and flat) hairs.
• silky: with adpressed, soft and straight pubescence.
• stellate, or stelliform: with star-shaped hairs.
• strigose: with appressed, sharp, straight and stiff hairs.
• tomentose: densely pubescent with matted, soft white woolly hairs.
  • cano-tomentose: between canescent and tomentose.
  • felted-tomentose: woolly and matted with curly hairs.
• villous: with long and soft hairs, usually curved.
• woolly:' with long, soft and tortuous or matted hairs.

Adaptations

The lists in this article may contain items that are not notable, not encyclopedic, or not helpful. Please help out by removing such elements and incorporating appropriate items into the main body of the article. (February 2008)

Poinsettia bracts are leaves which have evolved red pigmentation in order to attract insects and birds to the central flowers, an adaptive function normally served by petals (which are themselves leaves highly modified by evolution).

In the course of evolution, leaves have adapted to different environments in the following ways:

• A certain surface structure avoids moistening by rain and contamination (See Lotus effect).
• Sliced leaves reduce wind resistance.
• Hairs on the leaf surface trap humidity in dry climates and create a boundary layer reducing water loss.
• Waxy leaf surfaces reduce water loss.
• Large surface area provides large area for sunlight and shade for plant to minimize heating and reduce water loss.
• In more or less opaque or buried in the soil leaves, translucent windows filter the light before the photosynthesis takes place at the inner leaf surfaces (e.g. Fenestraria).
• Succulent leaves store water and organic acids for use in CAM photosynthesis.
• Aromatic oils, poisons or pheromones produced by leaf borne glands deter herbivores (e.g. eucalypts).
• Inclusions of crystalline minerals deter herbivores (e.g. silica phytoliths in grasses, raphides in Araceae).
• Petals attracts pollinators.
• Spines protect the plants (e.g. cacti).
• Insect traps feed the plants directly (see carnivorous plants).
• Bulbs store food and water (e.g. onions).
• Tendrils allow the plant to climb (e.g. peas).
• Bracts and pseudanthia (false flowers) replace normal flower structures when the true flowers are greatly reduced (e.g. Spurges).

Interactions with other organisms

Some insects mimic leaves (Kallima inachus shown)

A girl playing with leaves

Leaf after being eaten by Caterpillar

Although not as nutritious as other organs such as fruit, leaves provide a food source for many organisms. Animals which eat leaves are known as folivores. The leaf is one of the most vital parts of the plant, and plants have evolved protection against folivores such as tannins, chemicals which hinder the digestion of proteins and have an unpleasant taste.

Some animals have cryptic adaptations to avoid their own predators. For example, some caterpillars will create a small home in the leaf by folding it over themselves, while other herbivores and their prey mimic the appearance of the leaf. Some insects, such as the katydid, take this even further, moving from side to side much like a leaf does in the wind. 

The circulatory system is an organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis.

This system may be seen strictly as a blood distribution network, but some consider the circulatory system as composed of the cardiovascular system, which distributes blood,^[1] and the lymphatic system,^[2] which distributes lymph. While humans, as well as other vertebrates, have a closed cardiovascular system (meaning that the blood never leaves the network of arteries, veins and capillaries), some invertebrate groups have an open cardiovascular system. The most primitive animal phyla lack circulatory systems. The lymphatic system, on the other hand, is an open system.

Two types of fluids move through the circulatory system: blood and lymph. The blood, heart, and blood vessels form the cardiovascular system. The lymph, lymph nodes, and lymph vessels form the lymphatic system. The cardiovascular system and the lymphatic system collectively make up the circulatory system.

Human cardiovascular system

The main components of the human cardiovascular system are the heart, the veins, and the blood vessels.^[3] It includes: the pulmonary circulation, a "loop" through the lungs where blood is oxygenated; and the systemic circulation, a "loop" through the rest of the body to provide oxygenated blood. An average adult contains five to six quarts (roughly 4.7 to 5.7 liters) of blood, which consists of plasma, red blood cells, white blood cells, and platelets. Also, the digestive system works with the circulatory system to provide the nutrients the system needs to keep the heart pumping.

Pulmonary circulation

The Pulmonary circulation is the portion of the cardiovascular system which transports oxygen-depleted blood away from the heart, to the lungs, and returns oxygenated blood back to the heart.

Oxygen deprived blood from the vena cava enters the right atrium of the heart and flows through the tricuspid valve into the right ventricle, from which it is pumped through the pulmonary semilunar valve into the pulmonary arteries which go to the lungs. Pulmonary veins return the now oxygen-rich blood to the heart, where it enters the left atrium before flowing through the mitral valve into the left ventricle. Then, oxygen-rich blood from the left ventricle is pumped out via the aorta, and on to the rest of the body.

Systemic circulation

Systemic circulation is the portion of the cardiovascular system which transports oxygenated blood away from the heart, to the rest of the body, and returns oxygen-depleted blood back to the heart. Systemic circulation is, distance-wise, much longer than pulmonary circulation, transporting blood to every part of the body.

Coronary circulation

The coronary circulatory system provides a blood supply to the heart. As it provides oxygenated blood to the heart, it is by definition a part of the systemic circulatory system.

Heart

View from the front, which means the right side of the heart is on the left of the diagram (and vice-versa)

The heart pumps oxygenated blood to the body and deoxygenated blood to the lungs. In the human heart there is one atrium and one ventricle for each circulation, and with both a systemic and a pulmonary circulation there are four chambers in total: left atrium, left ventricle, right atrium and right ventricle. The right atrium is the upper chamber of the right side of the heart. The blood that is returned to the right atrium is deoxygenated (poor in oxygen) and passed into the right ventricle to be pumped through the pulmonary artery to the lungs for re-oxygenation and removal of carbon dioxide. The left atrium receives newly oxygenated blood from the lungs as well as the pulmonary vein which is passed into the strong left ventricle to be pumped through the aorta to the different organs of the body.

Closed cardiovascular system

The cardiovascular systems of humans are closed, meaning that the blood never leaves the network of blood vessels. In contrast, oxygen and nutrients diffuse across the blood vessel layers and enters interstitial fluid, which carries oxygen and nutrients to the target cells, and carbon dioxide and wastes in the opposite direction. The other component of the circulatory system, the lymphatic system, is not closed.

Measurement techniques

• Electrocardiogram—for cardiac electrophysiology
• Sphygmomanometer and stethoscope—for blood pressure
• Pulse meter—for cardiac function (heart rate, rhythm, dropped beats)
• Pulse—commonly used to determine the heart rate in absence of certain cardiac pathologies
• Heart rate variability -- used to measure variations of time intervals between heart beats
• Nail bed blanching test—test for perfusion
• Vessel cannula or catheter pressure measurement—pulmonary wedge pressure or in older animal experiments.

Health and disease

Oxygen transportation

About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at sea-level pressure is chemically combined with haemoglobin molecules. About 1.5% is physically dissolved in the other blood liquids and not connected to haemoglobin. The haemoglobin molecule is the primary transporter of oxygen in mammals and many other species.

Nonhuman

Other vertebrates

The circulatory systems of all vertebrates, as well as of annelids (for example, earthworms) and cephalopods (squid and octopus) are closed, just as in humans. Still, the systems of fish, amphibians, reptiles, and birds show various stages of the evolution of the circulatory system.

In fish, the system has only one circuit, with the blood being pumped through the capillaries of the gills and on to the capillaries of the body tissues. This is known as single cycle circulation. The heart of fish is therefore only a single pump (consisting of two chambers).

In amphibians and most reptiles, a double circulatory system is used, but the heart is not always completely separated into two pumps. Amphibians have a three-chambered heart.

In reptiles, the ventricular septum of the heart is incomplete and the pulmonary artery is equipped with a sphincter muscle. This allows a second possible route of blood flow. Instead of blood flowing through the pulmonary artery to the lungs, the sphincter may be contracted to divert this blood flow through the incomplete ventricular septum into the left ventricle and out through the aorta. This means the blood flows from the capillaries to the heart and back to the capillaries instead of to the lungs. This process is useful to ectothermic (cold-blooded) animals in the regulation of their body temperature.

Birds and mammals show complete separation of the heart into two pumps, for a total of four heart chambers; it is thought that the four-chambered heart of birds evolved independently from that of mammals.

Open circulatory system

The Open Circulatory System is a system in which fluid (called hemolymph) in a cavity called the hemocoel bathes the organs directly with oxygen and nutrients and there is no distinction between blood and interstitial fluid; this combined fluid is called hemolymph or haemolymph. Muscular movements by the animal during locomotion can facilitate hemolymph movement, but diverting flow from one area to another is limited. When the heart relaxes, blood is drawn back toward the heart through open-ended pores (ostia).

Hemolymph fills all of the interior hemocoel of the body and surrounds all cells. Hemolymph is composed of water, inorganic salts (mostly Na⁺, Cl^-, K⁺, Mg²⁺, and Ca²⁺), and organic compounds (mostly carbohydrates, proteins, and lipids). The primary oxygen transporter molecule is hemocyanin.

There are free-floating cells, the hemocytes, within the hemolymph. They play a role in the arthropod immune system.

Absence of circulatory system

Circulatory systems are absent in some animals, including flatworms (phylum Platyhelminthes). Their body cavity has no lining or enclosed fluid. Instead a muscular pharynx leads to an extensively branched digestive system that facilitates direct diffusion of nutrients to all cells. The flatworm's dorso-ventrally flattened body shape also restricts the distance of any cell from the digestive system or the exterior of the organism. Oxygen can diffuse from the surrounding water into the cells, and carbon dioxide can diffuse out. Consequently every cell is able to obtain nutrients, water and oxygen without the need of a transport system.

Some animals, such as jellyfish, have more extensive branching from their gastrovascular cavity (which functions as both a place of digestion and a form of circulation), this branching allows for bodily fluids to reach the outer layers, since the digestion begins in the inner layers. 

Metabolism (from Greek μεταβολισμός (metabolismós), "outthrow") is the set of chemical reactions that happen in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter, for example to harvest energy in cellular respiration. Anabolism uses energy to construct components of cells such as proteins and nucleic acids.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, by a sequence of enzymes. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy and will not occur by themselves, by coupling them to spontaneous reactions that release energy. As enzymes act as catalysts they allow these reactions to proceed quickly and efficiently. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell's environment or signals from other cells.

The metabolism of an organism determines which substances it will find nutritious and which it will find poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals.^[1] The speed of metabolism, the metabolic rate, also influences how much food an organism will require.

A striking feature of metabolism is the similarity of the basic metabolic pathways and components between even vastly different species.^[2] For example, the set of carboxylic acids that are best known as the intermediates in the citric acid cycle are present in all organisms, being found in species as diverse as the unicellular bacteria Escherichia coli and huge multicellular organisms like elephants.^[3] These striking similarities in metabolism are probably due to the high efficiency of these pathways, and their early appearance in evolutionary history.

Amino acids and proteins

Proteins are made of amino acids arranged in a linear chain and joined together by peptide bonds. Many proteins are the enzymes that catalyze the chemical reactions in metabolism. Other proteins have structural or mechanical functions, such as the proteins that form the cytoskeleton, a system of scaffolding that maintains the cell shape.^[6] Proteins are also important in cell signaling, immune responses, cell adhesion, active transport across membranes, and the cell cycle.^[7]

Lipids

Lipids are the most diverse group of biochemicals. Their main structural uses are as part of biological membranes such as the cell membrane, or as a source of energy.^[7] Lipids are usually defined as hydrophobic or amphipathic biological molecules that will dissolve in organic solvents such as benzene or chloroform.^[8] The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acid esters is a triacylglyceride.^[9] Several variations on this basic structure exist, including alternate backbones such as sphingosine in the sphingolipids, and hydrophilic groups such as phosphate in phospholipids. Steroids such as cholesterol are another major class of lipids that are made in cells.^[10]

Carbohydrates

Glucose can exist in both a straight-chain and ring form.

Carbohydrates are straight-chain aldehydes or ketones with many hydroxyl groups that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals).^[7] The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.^[11]

Nucleotides

The two nucleic acids, DNA and RNA are polymers of nucleotides, each nucleotide comprising a phosphate group, a ribose sugar group, and a nitrogenous base. Nucleic acids are critical for the storage and use of genetic information, through the processes of transcription and protein biosynthesis.^[7] This information is protected by DNA repair mechanisms and propagated through DNA replication. Many viruses have an RNA genome, for example HIV, which uses reverse transcription to create a DNA template from its viral RNA genome.^[12] RNA in ribozymes such as spliceosomes and ribosomes is similar to enzymes as it can catalyze chemical reactions. Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic group transfer reactions.^[13]

Coenzymes

Structure of the coenzyme acetyl-CoA.The transferable acetyl group is bonded to the sulfur atom at the extreme left.

Metabolism involves a vast array of chemical reactions, but most fall under a few basic types of reactions that involve the transfer of functional groups.^[14] This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions.^[13] These group-transfer intermediates are called coenzymes. Each class of group-transfer reaction is carried out by a particular coenzyme, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. These coenzymes are therefore continuously being made, consumed and then recycled.^[15]

One central coenzyme is adenosine triphosphate (ATP), the universal energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day.^[15] ATP acts as a bridge between catabolism and anabolism, with catabolic reactions generating ATP and anabolic reactions consuming it. It also serves as a carrier of phosphate groups in phosphorylation reactions.

A vitamin is an organic compound needed in small quantities that cannot be made in the cells. In human nutrition, most vitamins function as coenzymes after modification; for example, all water-soluble vitamins are phosphorylated or are coupled to nucleotides when they are used in cells.^[16] Nicotinamide adenine dinucleotide (NADH), a derivative of vitamin B₃ (niacin), is an important coenzyme that acts as a hydrogen acceptor. Hundreds of separate types of dehydrogenases remove electrons from their substrates and reduce NAD⁺ into NADH. This reduced form of the coenzyme is then a substrate for any of the reductases in the cell that need to reduce their substrates.^[17] Nicotinamide adenine dinucleotide exists in two related forms in the cell, NADH and NADPH. The NAD⁺/NADH form is more important in catabolic reactions, while NADP⁺/NADPH is used in anabolic reactions.

Structure of hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. From PDB 1GZX.

Minerals and cofactors

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of mammals' mass are the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur.^[18] The organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen and most of the oxygen and hydrogen is present as water.^[18]

The abundant inorganic elements act as ionic electrolytes. The most important ions are sodium, potassium, calcium, magnesium, chloride, phosphate, and the organic ion bicarbonate. The maintenance of precise gradients across cell membranes maintains osmotic pressure and pH.^[19] Ions are also critical for nerves and muscles, as action potentials in these tissues are produced by the exchange of electrolytes between the extracellular fluid and the cytosol.^[20] Electrolytes enter and leave cells through proteins in the cell membrane called ion channels. For example, muscle contraction depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and T-tubules.^[21]

The transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant.^[22][23] These metals are used in some proteins as cofactors and are essential for the activity of enzymes such as catalase and oxygen-carrier proteins such as hemoglobin.^[24] These cofactors are bound tightly to a specific protein; although enzyme cofactors can be modified during catalysis, cofactors always return to their original state after catalysis has taken place. The metal micronutrients are taken up into organisms by specific transporters and bound to storage proteins such as ferritin or metallothionein when not being used. 

The cell is the functional basic unit of life. It was discovered by Robert Hooke and is the functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life.^[1] Some organisms, such as most bacteria, are unicellular (consist of a single cell). Other organisms, such as humans, are multicellular. Humans have about 100 trillion or 10¹⁴ cells; a typical cell size is 10 µm and a typical cell mass is 1 nanogram. The largest cells are about 135 µm in the anterior horn in the spinal cord while granule cells in the cerebellum, the smallest, can be some 4 µm and the longest cell can reach from the toe to the lower brain stem (Pseudounipolar cells).^[2] The largest known cells are unfertilised ostrich egg cells which weigh 3.3 pounds.^[3][4]

In 1835, before the final cell theory was developed, Jan Evangelista Purkyně observed small "granules" while looking at the plant tissue through a microscope. The cell theory, first developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells, that all cells come from preexisting cells, that vital functions of an organism occur within cells, and that all cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells.^[5]

The word cell comes from the Latin cellula, meaning, a small room. The descriptive term for the smallest living biological structure was coined by Robert Hooke in a book he published in 1665 when he compared the cork cells he saw through his microscope to the small rooms monks lived in

Anabolism (from Greek ana, "upward", and ballein, "to throw") is the set of metabolic pathways that construct molecules from smaller units.^[1] These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite. Anabolism is powered by catabolism, where large molecules are broken down into smaller parts and then used up in respiration. Many anabolic processes are powered by adenosine triphosphate (ATP).^[2]

Anabolic processes tend toward "building up" organs and tissues. These processes produce growth and differentiation of cells and increase in body size, a process that involves synthesis of complex molecules. Examples of anabolic processes include the growth and mineralization of bone and increases in muscle mass.

Endocrinologists have traditionally classified hormones as anabolic or catabolic, depending on which part of metabolism they stimulate. The classic anabolic hormones are the anabolic steroids, which stimulate protein synthesis and muscle growth. The balance between anabolism and catabolism is also regulated by circadian rhythms, with processes such as glucose metabolism fluctuating to match an animal's normal periods of activity throughout the day.^[3]

Classic anabolic hormones

• Growth hormone
• IGF1 and other insulin-like growth factors
• Insulin
• Testosterone
• Estradiol

More recently discovered hormones associated with the balance of the catabolic and anabolic states include

• Orexin and Hypocretin (a hormone pair)
• Melatonin

In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g (0.02 oz.), in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica) covered by a dural fold (diaphragma sellae). The pituitary is functionally connected to the hypothalamus by the median eminence via a small tube called the infundibular stem (Pituitary Stalk). The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain. The pituitary gland secretes nine hormones that regulate homeostasis.

There is an analogous structure in the octopus brain.

Sections

The pituitary gland consists of two components: the anterior pituitary (or adenohypophysis) and the posterior pituitary (or neurohypophysis), and is functionally linked to the hypothalamus by the pituitary stalk (also named the "infundibular stem", or simply the "infundibulum")[1]. It is from the hypothalamus that hypothalamic tropic factors are released to descend down the pituitary stalk to the pituitary gland where they stimulate the release of pituitary hormones. While the pituitary gland is known as the 'master' endocrine gland, both of the lobes are under the control of the hypothalamus; the anterior pituitary receives its signals from the parvocellular neurons and the posterior pituitary receives its signals from magnocellular neurons ^[3]

Anterior pituitary (Adenohypophysis)

The anterior pituitary synthesizes and secretes the following important endocrine hormones:

• Adrenocorticotropic hormone (ACTH), release under influence of hypothalamic Corticotropin Releasing Hormone (CRH).
• Thyroid-stimulating hormone (TSH), release under influence of hypothalamic Thyrotropin Releasing Hormone (TRH).
• Growth hormone (also referred to as 'Human Growth Hormone', 'HGH' or 'GH' or somatotropin), release under influence of hypothalamic Growth Hormone Releasing Hormone (GHRH); inhibited by hypothalamic Somatostatin.
• Prolactin (PRL), also known as 'Luteotropic' hormone (LTH), release under influence of multiple hypothalamic Prolactin Releasing Factors (PRH).

The two 'Gonadotropins';

• Luteinizing hormone (also referred to as 'Lutropin' or 'LH', or in males, 'Interstitial Cell Stimulating Hormone' (ICSH)), and
• Follicle stimulating hormone (FSH), both released under influence of Gonadotropin Releasing Hormone (GnRH).

and;

• melanocyte–stimulating hormones (MSH's) or "intermedins" as these are released by the pars intermedia which is "the middle part"; adjacent to the posterior pituitary lobe, pars intermedia is a specific part developed from the anterior pituitary lobe.

These hormones are released from the anterior pituitary under the influence of the hypothalamus. Hypothalamic hormones are secreted to the anterior lobe by way of a special capillary system, called the hypothalamic-hypophysial portal system.

The anterior pituitary is divided into anatomical regions known as the pars tuberalis, pars intermedia, and pars distalis. It develops from a depression in the dorsal wall of the pharynx (stomodial part) known as Rathke's pouch.

Posterior pituitary (Neurohypophysis)

The posterior pituitary stores and releases:

• Oxytocin, most of which is released from the paraventricular nucleus in the hypothalamus
• Antidiuretic hormone (ADH, also known as vasopressin and AVP, arginine vasopressin), the majority of which is released from the supraoptic nucleus in the hypothalamus

Oxytocin is one of the few hormones to create a positive feedback loop. For example, uterine contractions stimulate the release of oxytocin from the posterior pituitary, which, in turn, increases uterine contractions. This positive feedback loop continues throughout labor.

Intermediate lobe

There is also an intermediate lobe in many animals, but is rudimentary in humans. For instance, in fish, it is believed to control physiological color change. In adult humans, it is just a thin layer of cells between the anterior and posterior pituitary. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.

Variations among vertebrates

The pituitary gland is found in all vertebrates, but its structure varies between different groups.

The division of the pituitary described above is typical of mammals, and is also true, to varying degrees, of all tetrapods. However, only in mammals does the posterior pituitary have a compact shape. In lungfishes it is a relatively flat sheet of tissue lying above the anterior pituitary, and in amphibians, reptiles and birds, it becomes increasingly well developed. The intermediate lobe is generally not well developed in tetrapods, and is entirely absent in birds.^[4]

Apart from lungfishes, the structure of the pituitary in fish is generally different from that in tetrapods. In general, the intermediate lobe tends to be well developed, and may equal the remainder of the anterior pituitary in size. The posterior lobe typically forms a sheet of tissue at the base of the pituitary stalk, and in most cases sends irregular finger-like projection into the tissue of the anterior pituitary, which lies directly beneath it. The anterior pituitary is typically divided into two regions, a more anterior rostral portion and a posterior proximal portion, but the boundary between the two is often not clearly marked. In elasmobranchs there is an additional, ventral lobe beneath the anterior pituitary proper.^[4]

The arrangement in lampreys, which are amongst the most primitive of all fish, may indicate how the pituitary originally evolved in ancestral vertebrates. Here, the posterior pituitary is a simple flat sheet of tissue at the base of the brain, and there is no pituitary stalk. Rathke's pouch remains open to the outside, close to the nasal openings. Closely associated with the pouch are three distinct clusters of glandular tissue, corresponding to the intermediate lobe, and the rostral and proximal portions of the anterior pituitary. These various parts are separated by meningial membranes, suggesting that the pituitary of other vertebrates may have formed from the fusion of a number of separate, but closely associated, glands.^[4]

Most fish also possess a urophysis, a neural secretory gland very similar in form to the posterior pituitary, but located in the tail and associated with the spinal cord. This may have a function in osmoregulation.^[4]

Functions

Hormones secreted from the pituitary gland help control the following body processes:

• Growth (Excess of HGH can lead to gigantism and acromegaly.)
• Blood pressure
• Some aspects of pregnancy and childbirth including stimulation of uterine contractions during childbirth
• Breast milk production
• Sex organ functions in both men and women
• Thyroid gland function
• The conversion of food into energy (metabolism)
• Water and osmolarity regulation in the body
• Water balance via the control of reabsorption of water by the kidneys
• Temperature regulation

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest. Parathyroid glands control the amount of calcium in the blood and within the bones.

Anatomy

Micrograph of a parathyroid gland.H&E stain.

The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface (back side) of the thyroid gland. The parathyroid glands usually weigh between 25mg and 40mg in humans. There are typically two, one above the other, on the left lobe of the thyroid and similarly on the right. The two parathyroid glands on each side which are positioned higher (closer to the head) are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Occasionally, some individuals may have six, eight, or even more parathyroid glands.

The parathyroid glands are named for their proximity to the thyroid but serve a completely different role than the thyroid gland. The parathyroid glands are quite easily recognizable from the thyroid as they have densely packed cells, in contrast with the follicle structure of the thyroid. ^[1] However, at surgery, they are harder to differentiate from the thyroid or fat.

In the histological sense, they distinguish themselves from the thyroid gland, as they contain two types of cells:^[2]

Name	Staining	Quantity	Size	Function
parathyroid chief cells	darker	many	smaller	manufacture PTH (see below).
oxyphil cells	lighter	few	larger	function unknown.[3]

Guanine (G) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. With the formula C₅H₅N₅O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar. The guanine nucleoside is called guanosine.

Basic principles

Guanine, along with adenine and cytosine, is present in both DNA and RNA, whereas thymine is usually seen only in DNA, and uracil only in RNA. Guanine has twotautomeric forms, the major keto form (see figures) and rare enol form. It binds to cytosine through three hydrogen bonds. In cytosine, the amino group acts as the hydrogen donor and the C-2 carbonyl and the N-3 amine as the hydrogen-bond acceptors. Guanine has a group at C-6 that acts as the hydrogen acceptor, while the group at N-1 and the amino group at C-2 act as the hydrogen donors.

The first isolation of guanine was reported in 1844 from the excreta of sea birds,^[2] known as guano, which was used as a source of fertilizer. About fifty years later, Fischer determined the structure and also showed that uric acid can be converted to guanine.

Guanine can be hydrolyzed with strong acid to glycine, ammonia, carbon dioxide, and carbon monoxide. Guanine is first deaminated to xanthine.^[3] Guanine oxidizes more readily than adenine, the other purine-derivative base in DNA. Its high melting point of 350°C reflects the intermolecular hydrogen bonding between the oxo and amino groups in the molecules in the crystal. Because of this intermolecular bonding, guanine is relatively insoluble in water, but it is soluble in dilute acids and bases.

Syntheses

Trace amounts of guanine form by the polymerization of ammonium cyanide (NH₄CN). Two experiments conducted by Levy et al. showed that heating 10 mol·L⁻¹NH₄CN at 80 °C for 24 hours gave a yield of 0.0007%, while using 0.1 mol·L⁻¹ NH₄CN frozen at -20 °C for 25 years gave a 0.0035% yield. These results indicate guanine could arise in frozen regions of the primitive earth. In 1984, Yuasa reported a 0.00017% yield of guanine after the electrical discharge of NH₃, CH₄, C₂H₆, and 50 mL of water, followed by a subsequent acid hydrolysis. However, it is unknown whether the presence of guanine was not simply a resultant contaminant of the reaction.^[4]

5NH₃ + CH₄ + 2C₂H₆ + H₂O → C₅H₈N₅O (guanine) + (25/2)H₂

A Fischer-Tropsch synthesis can also be used to form guanine, along with adenine, uracil, and thymine. Heating an equimolar gas mixture of CO, H₂, and NH₃ to 700 °C for 15 to 24 minutes, followed by quick cooling and then sustainted reheating to 100 to 200 °C for 16 to 44 hours with an alumina catalyst, yielded guanine and uracil:

5CO + (1/2)H₂ + 5NH₃ → C₅H₈N₅O (guanine) + 4H₂O

Another possible abiotic route was explored by quenching a 90% N₂–10%CO–H₂O gas mixture high-temperature plasma ^[5]

Traube's synthesis involves heating 2,4,5-triamino-1,6-dihydro-6-oxypyrimidine (as the sulfate) with formic acid for several hours. 

Other uses

Guanine etymologically comes via the Quichua word "huanu" for dung from the Spanish loan word "guano". As the Oxford English Dictionary notes, guanine is "A white amorphous substance obtained abundantly from guano, forming a constituent of the excrement of birds".^[6]

In 1656 in Paris, François Jaquin (a rosary maker) extracted from scales of some fishes the so-called pearl essence, crystalline guanine forming G-quadruplexes. In the cosmetics industry, crystalline guanine is used as an additive to various products (e.g., shampoos), where it provides a pearly iridescent effect. It is also used in metallic paints and simulated pearls and plastics. It provides shimmering luster to eye shadow and nail polish. Facial treatments using the droppings, or guano, from Japanese nightingales is currently in favor in New York, reportedly because the guanine in the droppings produces a clear, "bright" skin tone^[7]that some people find desirable to attain. Guanine crystals are rhombic platelets composed of multiple transparent layers, but they have a high index of refraction that partially reflects and transmits light from layer to layer, thus producing a pearly luster. It can be applied by spray, painting, or dipping. It may irritate the eyes. Its alternatives are mica, faux pearl (from ground shells),^[8] and aluminium and bronze particles.

Spiders and scorpions convert ammonia, as a product of protein metabolism in the cells, to guanine as it can be excreted with minimal water loss.

Guanine is found in integumentary system of many fish such as sturgeon.^[9] It is also present in the reflective deposits of the eyes of deep-sea fish and some reptiles such as crocodiles. 

What is Evolution?

Biological evolution is defined as any genetic change in a population that is inherited over several generations. These changes may be small or large, noticeable or not so noticeable.

In order for an event to be considered an instance of evolution, changes have to occur on the genetic level of a population and be passed on from one generation to the next. 

This means that the genes, or more specifically, the alleles in the population change and are passed on. These changes are noticed in the phenotypes (expressed physical traits that can be seen) of the population. 

A change on the genetic level of a population is defined as a small-scale change and is called microevolution. 

Biological evolution also includes the idea that all of life is connected and can be traced back to one common ancestor. This is called macroevolution.

What is not Evolution?

Biological evolution is not defined as simply change over time. 

Many organisms experience changes over time, such as weight loss or gain. These changes are not considered instances of evolution because they are not genetic changes that can be passed on to the next generation.

Is Evolution a Theory?

Evolution is a scientific theory that was proposed by Charles Darwin. A scientific theory gives explanations and predictions for naturally occurring phenomena based on observations and experimentations. This type of theory attempts to explain how events seen in the natural world work.

The definition of a scientific theory differs from the common meaning of theory, which is defined as a guess or a supposition about a particular process. In contrast, a good scientific theory must be testable, falsifiable, and substantiated by factual evidence. 

When it comes to a scientific theory, there is no absolute proof. It's more a case of confirming the reasonability of accepting a theory as a viable explanation for a particular event.

What is Natural Selection?

Natural selection is the process by which biological evolutionary changes take place. Natural selection acts on populations and not individuals. It is based on the following concepts:

·         Individuals in a population have different traits which can be inherited.

·         These individuals produce more young than the environment can support.

·         The individuals in a population that are best suited to their environment will leave more offspring, resulting in a change in the genetic makeup of a population.

The genetic variations that arise in a population happen by chance, but the process of natural selection does not. Natural selection is the result of the interactions between genetic variations in a population and the environment.

The environment determines which variations are more favorable. Individuals that possess traits that are better suited to their environment will survive to produce more offspring than other individuals. More favorable traits are thereby passed on to the population as a whole.

How Does Genetic Variation Occur in a Population?

Genetic variation occurs through sexual reproduction. Due to the fact that environments are unstable, populations that are genetically variable will be able to adapt to changing situations better than those that do not contain genetic variations.

Sexual reproduction allows for genetic variations to occur through genetic recombination. 

Recombination occurs during meiosis and provides a way for producing new combinations of alleles on a single chromosome. Independent assortment during meiosis allows for an indefinite number of combinations of genes. (Example of recombination) 

Sexual reproduction makes it possible to assemble favorable gene combinations in a population or to remove unfavorable gene combinations from a population. Populations with more favorable genetic combinations will survive in their environment and reproduce more offspring than those with less favorable genetic combinations.

Biological Evolution Versus Creation

The theory of evolution has caused controversy from the time of its introduction until today. The controversy stems from the perception that biological evolution is at odds with religion concerning the need for a divine creator. Evolutionists contend that evolution does not address the issue of whether or not God exists, but attempts to explain how natural processes work.

In doing so however, there is no escaping the fact that evolution contradicts certain aspects of some religious beliefs. For example, the evolutionary account for the existence of life and the biblical account of creation are quite different.

Evolution suggests that all life is connected and can be traced back to one common ancestor. A literal interpretation of biblical creation suggests that life was created by an all powerful, supernatural being (God). 

Still others have tried to merge these two concepts by contending that evolution does not exclude the possibility of the existence of God, but merely explains the process by which God created life. This view however, still contradicts a literal interpretation of creation as presented in the bible.

In paring down the issue, a major bone of contention between the two views is the concept of macroevolution. For the most part, evolutionists and creationists agree that microevolution does occur and is visible in nature.

Macroevolution however, refers to the process of evolution that takes place on the level of species, in which one species evolves from another species. This is in stark contrast to the biblical view that God was personally involved in the formation and creation of living organisms.

For now, the evolution/creation debate continues on and it appears that the differences between these two views are not likely to be settled any time soon.

Bones are rigid organs that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue. Because bones come in a variety of shapes and have a complex internal and externalstructure they are lightweight, yet strong and hard, in addition to fulfilling their many other functions. One of the types of tissue that makes up bone is the mineralizedosseous tissue, also called bone tissue, that gives it rigidity and a honeycomb-like three-dimensional internal structure. Other types of tissue found in bones includemarrow, endosteum and periosteum, nerves, blood vessels and cartilage. There are 206 bones in the adult human body^[1] and 270 in an infant. The largest bone in the human body is the femur.

The primary tissue of bone, osseous tissue, is a relatively hard and lightweight composite material, formed mostly of calcium phosphate in the chemical arrangement termed calcium hydroxylapatite (this is theosseous tissue that gives bones their rigidity). It has relatively high compressive strength, of about 170 MPa (1800 kgf/cm²)^[4] but poor tensile strength of 104-121 MPa, meaning it resists pushing forces well, but not pulling forces. While bone is essentially brittle, it does have a significant degree of elasticity, contributed chiefly by collagen. All bones consist of living and dead cells embedded in the mineralized organic matrixthat makes up the osseous tissue. 

The blastula (from Greek βλαστός (blastos), meaning "sprout") is an early stage of embryonic development in animals. It is also called blastosphere. It is produced by cleavage of a fertilized ovum and consists of a spherical layer of around 128 cells with a large fluid filled-space called the blastocoele in the animal pole of the embryo. The blastula follows the morula and precedes the gastrula in the developmental sequence.

In mammals, blastulation leads to the formation of the blastocyst, which must not be confused with the blastula. The blastocyst contains an embryoblast, which is homologous to the blastula. However, it also includes the trophoblast, which goes on to form the extraembryonic tissues. 

Unlike previous treatments for infections, which included poisons such as or Gram-positive bacteria, while 'wide-spectrum' antibiotics affect a larger range of bacteria.

The effectiveness of individual antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the bacteria to resist or inactivate the antibiotic. Some antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic) so that the host's immune system can overcome them.

Oral antibiotics are the simplest approach when effective, with intravenous antibiotics reserved for more serious cases. Antibiotics may sometimes be administered topically, as with eyedrops or ointments.

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

Timeline Of Antibiotics

Many ancient cultures, including the Ancient Greeks and Ancient Chinese , already used Mould s and other plants to treat Infection . This worked because some moulds produce antibiotic substances. However, they couldn't distinguish or distill the active component in the moulds.

A barnacle is a type of arthropod belonging to infraclass Cirripedia in the subphylum Crustacea, and is hence related to crabs and lobsters. Barnacles are exclusively marine, and tend to live in shallow and tidal waters, typically in erosive settings. They are sessile suspension feeders, and have two nektonic larval stages. Around 1,220 barnacle species are currently known.^[1] The name "Cirripedia" is Latin, meaning "curl-footed".

Ecology

Semibalanus balanoidesfeeding

Barnacles are encrusters, attaching themselves permanently to a hard substrate. The most common, "acorn barnacles" (Sessilia) aresessile, growing their shells directly onto the substrate.^[2] The order Pedunculata ("goose barnacles" and others) attach themselves by means of a stalk.^[2]

Most barnacles are suspension feeders; they dwell continually in their shell — which is usually constructed of six plates^[2] — and reach into the water column with modified legs. These feathery appendages beat rhythmically to draw plankton and detritus into the shell for consumption.^[3]

Other members of the class have quite a different mode of life. For example, members of the genus Sacculina are parasitic, dwelling within crabs.^[4]

Although they have been found at water depths up to 600 m (2,000 ft),^[2] most barnacles inhabit shallow waters, with 75% of species living in water depths of less than 100 m (300 ft),^[2] and 25% inhabiting the intertidal zone.^[2] Within the intertidal zone, different species of barnacle live in very tightly constrained locations, allowing the exact height of an assemblage above or below sea level to be precisely determined.^[2]

Since the intertidal zone periodically desiccates, barnacles are well adapted against water loss. Their calcite shells are impermeable, and they possess two plates which they can slide across their aperture when not feeding. These plates also protect against predation.^[5]

Barnacles and limpets compete for space in the intertidal zone.

Barnacles are displaced by limpets and mussels, who compete for space. They also have numerous predators.^[2] They employ two strategies to overwhelm their competitors: "swamping" and fast growth. In the swamping strategy, vast numbers of barnacles settle in the same place at once, covering a large patch of substrate, allowing at least some to survive in the balance of probabilities.^[2] Fast growth allows the suspension feeders to access higher levels of the water column than their competitors, and to be large enough to resist displacement; species employing this response, such as the aptly named Megabalanus, can reach 7 cm (2.8 in) in length;^[2] other species may grow larger still (Austromegabalanus psittacus).

Competitors may include other barnacles, and there is (disputed) evidence that balanoid barnacles competitively displaced chthalamoid barnacles. Balanoids gained their advantage over the chthalamoids in the Oligocene, when they evolved a tubular skeleton. This provides better anchorage to the substrate, and allows them to grow faster, undercutting, crushing and smothering the latter group.^[6]

Among the most common predators on barnacles are whelks. They are able to grind through the calcareous exoskeletons of barnacles and feed on the softer inside parts. Mussels also prey on barnacle larvae.^[7] Another predator on barnacles is the starfish species Pisaster ochraceus.^[8][9]

Adult anatomy

Goose barnacles, with their cirriextended for feeding

Free-living barnacles are attached to the substratum by cement glands that form from the base of the first pair of antennae; in effect, the animal is fixed upside down by means of its forehead. In some barnacles, the cement glands are fixed to a long muscular stalk, but in most they are part of a flat membrane or calcified plate. A ring of plates surrounds the body, homologous with the carapace of other crustaceans. In sessile barnacles, the apex of the ring of plates is covered by an operculum, which may be recessed into the carapace. The plates are held together by various means, depending on species, in some cases being solidly fused.

Inside the carapace, the animal lies on its back, with its limbs projecting upwards. Segmentation is usually indistinct, and the body is more or less evenly divided between the head and thorax, with little, if any, abdomen. Adult barnacles have few appendages on the head, with only a single, vestigial, pair of antennae, attached to the cement gland. There are six pairs of thoracic limbs, referred to as "cirri", which are feathery and very long, being used to filter food from the water and move it towards the mouth.

Barnacles have no true heart, although a sinus close to the oesophagus performs similar function, with blood being pumped through it by a series of muscles. The blood vascular system is minimal. Similarly, they have no gills, absorbing oxygen from the water through their limbs and the inner membrane of the carapace. The excretory organs of barnacles are maxillary glands.

The main sense of barnacles appears to be touch, with the hairs on the limbs being especially sensitive. The adult also has a single eye, although this is probably only capable of sensing the difference between light and dark.^[10] This eye is derived from the primary naupliar eye.^[11]

Parasitic barnacles

The anatomy of parasitic barnacles is generally simpler than that of their free-living relatives. They have no carapace or limbs, having only an unsegmented sac-like body. Such barnacles feed by extending thread-like rhizomes of living cells into the host's body from their point of attachment.^[10]

Life cycle

Barnacles have 2 distinct larval stages, the nauplius and the cyprid, before developing into a mature adult.

Nauplius

A fertilised egg hatches into a nauplius: a one eyed larva comprising a head and a telson, without a thorax or abdomen. This undergoes 6 months of growth before transforming into the cyprid stage. Nauplii are typically initially brooded by the parent, and released as free-swimming larvae after the first moult.

The barnacle cyprid larva

Cyprid stage

Main article: Cyprid

The cyprid stage lasts from days to weeks. During this part of the life cycle, the barnacle searches for a place to settle. It explores potential surfaces with modified antennules; once it has found a potentially suitable spot, it attaches head-first using its antennules, and a secreted glycoproteinous substance. Larvae are thought to assess surfaces based upon their surface texture, chemistry, relative wettability, colour and the presence/absence and composition of a surface biofilm; swarming species are also more likely to attach near to other barnacles. As the larva exhausts its finite energy reserves, it becomes less selective in the sites it selects. If the spot is to its liking it cements down permanently with another proteinacous compound. This accomplished, it undergoes metamorphosis into a juvenile barnacle.

Adult stage

Typical acorn barnacles develop six hard calcareous plates to surround and protect their bodies. For the rest of their lives they are cemented to the ground, using their feathery legs (cirri) to capture plankton.

Once metamorphosis is over and they have reached their adult form, barnacles will continue to grow by adding new material to their heavily calcified plates. These plates are notmoulted; however, like all ecdysozoans, the barnacle itself will still molt its cuticle.^[12]

Sexual reproduction

Most barnacles are hermaphroditic, although a few species are gonochoric or androdioecious. The ovaries are located in the base or stalk, and may extend into the mantle, while the testes are towards the back of the head, often extending into the thorax. Typically, recently molted hermaphroditic individuals are receptive as females. Self-fertilization, although theoretically possible, has been experimentally shown to be rare in barnacles.^[13][14]

The sessile lifestyle of barnacles makes sexual reproduction difficult, as the organisms cannot leave their shells to mate. To facilitate genetic transfer between isolated individuals, barnacles have extraordinarily longpenises. Barnacles have the largest penis to body size ratio of the animal kingdom.^[13]

Fossil record

Miocene (Messinian) Megabalanus, smothered by sand and fossilised

The geological history of barnacles can be traced back to the Middle Cambrian (in the order of 500–510 million years ago),^[15] although they do not become common as skeletal remains in the fossil record until the Neogene (last 20 million years).^[2] In part their poor skeletal preservation is due to their restriction to high-energy environments, which tend to be erosional - therefore it is more common for their shells to be ground up by wave action than for them to reach a depositional setting. Trace fossils of acrothoracican barnacle borings (Rogerella) are common in the fossil record from the Devonian to the Recent.

Barnacles can play an important role in estimating palæo-water depths. The degree of disarticluation of fossils suggests the distance they have been transported, and since many species have narrow ranges of water depths, it can be assumed that the animals lived in shallow water and broke up as they were washed down-slope. The completeness of fossils, and nature of damage, can thus be used to constrain the tectonic history of regions.^[2]

In human culture

Corrosion caused by barnacles, considered biofouling

Barnacles were first fully studied and classified by Charles Darwin who published a series of monographs in 1851 and 1854. Darwin undertook this study at the suggestion of his friend Joseph Dalton Hooker, in order to thoroughly understand at least one species before making the generalisations needed for his theory of evolution by natural selection.^[16] Historian of science and novelist Rebecca Stott published a detailed account of Darwin's eight years studying barnacles in a book called Darwin and the Barnacle (Faber, 2003). The book challenges the supposition that Darwin was using the barnacle project as a way of delaying writing the book which would become On the Origin of Species.

Barnacles are of economic consequence as they often attach themselves to man-made structures, sometimes to the structure's detriment. Particularly in the case of ships, they are classified as fouling organisms.^[17]

Some barnacles are considered edible by humans, and goose barnacles (e.g. Pollicipes pollicipes), in particular, are treasured as a delicacy in Spain and Portugal.^[18] The resemblance of this barnacle's fleshy stalk to a goose's neck gave rise in ancient times to the notion that geese, or at least certain seagoing species of wild goose, literally grew from the barnacle. Indeed, the word "barnacle" originally referred to a species of goose, the Barnacle goose Branta leucopsis, whose eggs and young were rarely seen by humans because it breeds in the remote Arctic.^[19]

The picoroco barnacle is used in Chilean cuisine and is one of the ingredients in curanto.

Classification

Some authorities regard Cirripedia as a full class or subclass, and the orders listed above are sometimes treated as superorders. This article follows Martin and Davis in placing Cirripedia as an infraclass ofThecostraca and in the following classification of cirripedes down to the level of orders:^[20]

Semibalanus balanoides (Thoracica:Sessilia) feeding

Infraclass Cirripedia Burmeister, 1834

• Superorder Acrothoracica Gruvel, 1905
  • Order Pygophora Berndt, 1907
  • Order Apygophora Berndt, 1907
• Superorder Rhizocephala Müller, 1862
  • Order Kentrogonida Delage, 1884
  • Order Akentrogonida Häfele, 1911
• Superorder Thoracica Darwin, 1854
  • Order Pedunculata Lamarck, 1818
  • Order Sessilia Lamarck, 1818

A tadpole, polliwog (also pollywog, polliwig, polwig, or purwiggy), or pollywiggle (also polliwiggle, polwiggle, or porwiggle) is the wholly aquatic larval stage in the life cycle of an amphibian, particularly of a frog or toad.

Appellation

The name "tadpole" is from Middle English taddepol, made up of the elements tadde, "toad", and pol, "head" (modern English "poll"). Similarly, "polliwog" and "pollywiggle" are from Middle English polwigle, made up of the same pol, "head" and wiglen, "to wiggle".

General description

Metamorphosis of Bufo bufo.

Tadpole stage of Haswell's Frog.

Tadpoles are young amphibians that live in the water. During the tadpole stage of the amphibian life cycle, most respire by means of autonomous external or internal gills. They do not usually have arms or legs until the transition to adulthood, and typically have dorsal or fin-like appendages and a tail with which they swim by lateral undulation, similar to most fishes.

As a tadpole matures, it most commonly metamorphosizes by gradually growing limbs (usually the legs first, followed by the arms) and then (most commonly in the case of frogs) outwardly absorbing its tail by apoptosis. Lungs develop around the time of leg development, and tadpoles late in development will often be found near the surface of the water, where they breathe air. During the final stages of external metamorphosis, the tadpole's mouth changes from a small, enclosed mouth at the front of the head to a large mouth the same width as the head. The intestines shorten to make way for the new diet.^[1] Tadpoles are consumers. Most tadpoles are herbivorous, subsisting on algae and plants. Some species are omnivorous, eating detritus and, when available, smaller tadpoles.^[2] However, other tadpoles are normally safe from cannibalistic predation because all tadpoles in a given body of water are the same age and, therefore, the same size.

An exception to the rule of distinct differences between the tadpole (juvenile) and adult (frog, toad, salamander, etc.) stages is the axolotl. Axolotls exhibit a property called neoteny, meaning that they reach sexual maturity without undergoing metamorphosis.

Juvenile frog in transition between tadpole and frog

Fossil record

Remarkably, despite their soft-bodied nature and lack of mineralised hard parts, fossil tadpoles (around 10 cm in length) have been recovered from Upper Miocene strata.^[3] They are preserved by virtue of biofilms, with more robust structures (the jaw & bones) preserved as a carbon film.^[4] In Miocene fossils from Libros, Spain, the brain case is preserved in calcium carbonate, and the nerve cord in calcium phosphate. Other parts of the tadpoles' bodies exist as organic remains and bacterial biofilms, with sedimentary detritus present in the gut. ^[3] Tadpole remains with telltale external gills are also known from several of the Labyrinthodont groups. 

Amphibians (class Amphibia, from Amphi- meaning "on both sides" and -bios meaning "life"), such as frogs, toads, salamanders, newts, and caecilians, are ectothermic (or cold-blooded) animals that metamorphose from a juvenile water-breathing form, either to an adult air-breathing form, or to a paedomorph that retains some juvenile characteristics. Proteidae (mudpuppies and waterdogs) are good examples of paedomorphic species. Though amphibians typically have four limbs, the caecilians are notable for being limbless. Unlike other land vertebrates (amniotes), most amphibians lay eggs in water. Amphibians are superficially similar to reptiles.

Amphibians are ecological indicators, and in recent decades there has been a dramatic decline in amphibian populations around the globe. Many species are now threatened or extinct.

Amphibians evolved in the Devonian Period and were top predators in the Carboniferous and Permian Periods, but many lineages were wiped out during the Permian–Triassic extinction. One group, the metoposaurs, remained important predators during the Triassic, but as the world became drier during the Early Jurassic they died out, leaving a handful of relict temnospondyls like Koolasuchus and the modern orders of Lissamphibia.

Etymology

Amphibian is derived from the Ancient Greek term ἀμφίβιος amphíbios which means both kinds of life, amphi meaning “both” and bio meaning life. The term was initially used for all kinds of combined natures. Eventually it was used to refer to animals that live both in the water and on land.^[1]

Evolutionary history

The first major groups of amphibians developed in the Devonian Period from fish similar to the modern coelacanth and lungfish which had evolved multi-jointed leg-like fins that enabled them to crawl along the sea bottom. These amphibians were as much as one to five meters in length. However, amphibians never developed the ability to live their entire lives on land, having to return to water to lay their shell-less eggs.

In the Carboniferous Period, the amphibians moved up in the food chain and began to occupy the ecological position currently occupied by crocodiles. These amphibians were notable for eating the mega insects on land and many types of fishes in the water. During the Triassic Period, the better land-adapted proto-crocodiles began to compete with amphibians, leading to their reduction in size and importance in the biosphere.

Taxonomic history

Traditionally, amphibians have included all tetrapod vertebrates that are not amniotes. They are divided into three subclasses, of which two are only known as extinct subclasses:

• Subclass Labyrinthodontia† (diverse Paleozoic and early Mesozoic group)
• Subclass Lepospondyli† (small Paleozoic group, sometimes included in the Labyrinthodontia)
• Subclass Lissamphibia (frogs, toads, salamanders, newts, etc.)

Of these only the last subclass includes recent species.

With the phylogenetic classification Labyrinthodontia has been discarded as it is a paraphyletic group without unique defining features apart from shared primitive characteristics. Classification varies according to the preferred phylogeny of the author, whether they use a stem-based or node-based classification. Generally amphibians are defined as the group that includes the common ancestors of all living amphibians (frogs, salamanders and caecilians) and all their descendants. This may also include extinct groups like the temnospondyls (traditionally placed in the subclass “Labyrinthodontia”), and the Lepospondyls. This means that cladistic nomenklature list a large number of basal Devonian and Carboniferous tetrapod groups, undoubtedly were “amphibians” in biology, that are formally placed in Amphibia in Linnaean taxonomy, but not in cladistic taxonomy.

All recent amphibians are included in the subclass Lissamphibia, superorder Salientia, which is usually considered a clade (which means that it is thought that they evolved from a common ancestor apart from other extinct groups), although it has also been suggested that salamanders arose separately from a temnospondyl-like ancestor.^[2]

Authorities also disagree on whether Salientia is a Superorder that includes the order Anura, or whether Anura is a sub-order of the order Salientia. Practical considerations seem to favor using the former arrangement now. The Lissamphibia, superorder Salientia, are traditionally divided into three orders, but an extinct salamander-like family, the Albanerpetontidae, is now considered part of the Lissamphibia, besides the superorder Salientia. Furthermore, Salientia includes all three recent orders plus a single Triassic proto-frog, Triadobatrachus.

Class Amphibia

• Subclass Lissamphibia
  • • Family Albanerpetontidae — Jurassic to Miocene (extinct)
  • Superorder Salientia
    • Genus Triadobatrachus — Triassic (extinct)
    • Order Anura (frogs and toads): Jurassic to recent — 5,602 recent species in 48 families
    • Order Caudata or Urodela (salamanders, newts): Jurassic to recent — 571 recent species in 9 families
    • Order Gymnophiona or Apoda (caecilians): Jurassic to recent — 174 recent species in 3 families

The actual number of species partly also depends on the taxonomic classification followed, the two most common classifications being the classification of the website AmphibiaWeb, University of California (Berkeley) and the classification by herpetologist Darrel Frost and The American Museum of Natural History, available as the online reference database Amphibian Species of the World.^[3] The numbers of species cited above follow Frost.

Respiration

The lungs in amphibians are primitive compared to that of the amniotes, possessing few internal septa, large alveoli and therefore a slow diffusion rate of oxygen into the blood. Ventilation is accomplished by buccal pumping. However, most amphibians are able to exchange gasses with the water or air via their skin. To enable sufficient cutaneous respiration, the surface of their highly vascularized skin must remain moist in order for the oxygen to diffuse at a sufficient rate. Because oxygen concentration in the water increases at both low temperatures and high flow rates, aquatic amphibians in these situations can rely primarily on cutaneous respiration, as in the Titicaca water frog or hellbender salamanders. In air, where oxygen is more concentrated, some small species can rely solely on cutaneous gas exchange, most famously the plethodontid salamanders which have neither lungs nor gills. Many aquatic salamanders and all tadpoles have gills in their larval stage, with some (such as the axolotl) retaining gills as aquatic adults.

Reproductive system

Caecilian from the San Antonio zoo

For the purpose of reproduction most amphibians require fresh water. A few (e.g. Fejervarya raja) can inhabit brackish water and even survive (though not thrive) in seawater, but there are no true marine amphibians. Several hundred frog species in adaptive radiations (e.g., Eleutherodactylus, the Pacific Platymantines, the Australo-Papuan microhylids, and many other tropical frogs), however, do not need any water for breeding in the wild. They reproduce via direct development, an ecological and evolutionary adaptation that has allowed them to be completely independent from free-standing water. Almost all of these frogs live in wet tropical rainforests and their eggs hatch directly into miniature versions of the adult, passing through the tadpole stage within the egg. Several species have also adapted to arid and semi-arid environments, but most of them still need water to lay their eggs. Symbiosis with single celled algae that lives in the jelly-like layer of the eggs has evolved several times. The larvae (tadpoles or polliwogs) breathe with exterior gills. After hatching, they start to transform gradually into the adult's appearance. This process is called metamorphosis. Typically, the animals then leave the water and become terrestrial adults, but there are many interesting exceptions to this general way of reproduction.

The most obvious part of the amphibian metamorphosis is the formation of four legs in order to support the body on land. But there are several other changes:

• The gills are replaced by other respiratory organs, i.e., lungs.
• The skin changes and develops glands to avoid dehydration.
• The eyes develop eyelids and adapt to vision outside the water.
• An eardrum is developed to lock the middle ear.
• In frogs and toads, the tail disappears.

Conservation

The Golden Toad of Monteverde, Costa Rica was among the first casualties of amphibian declines. Formerly abundant, it was last seen in 1989.

Dramatic declines in amphibian populations, including population crashes and mass localized extinction, have been noted in the past two decades from locations all over the world, and amphibian declines are thus perceived as one of the most critical threats to global biodiversity. A number of causes are believed to be involved, including habitat destruction and modification, over-exploitation, pollution, introduced species, climate change, endocrine-disrupting pollutants, destruction of the ozone layer (ultraviolet radiation has shown to be especially damaging to the skin, eyes, and eggs of amphibians), and diseases like chytridiomycosis. However, many of the causes of amphibian declines are still poorly understood, and are a topic of ongoing discussion. A global strategy to stem the crisis has been released in the form of the Amphibian Conservation Action Plan (available at http://www.amphibians.org). Developed by over 80 leading experts in the field, this call to action details what would be required to curtail amphibian declines and extinctions over the next 5 years - and how much this would cost. The Amphibian Specialist Group of the World Conservation Union (IUCN) is spearheading efforts to implement a comprehensive global strategy for amphibian conservation.

On January 21, 2008, Evolutionarily Distinct and Globally Endangered (EDGE), as given by chief Helen Meredith, identified nature's most endangered species: "The EDGE amphibians are amongst the most remarkable and unusual species on the planet and yet an alarming 85% of the top 100 are receiving little or no conservation attention." The top 10 endangered species (in the List of endangered animal species) include: the Chinese giant salamander, a distant relative of the newt, the tiny Gardiner's Seychelles, the limbless Sagalla caecilian, South African ghost frogs, lungless Mexican salamanders, the Malagasy rainbow frog, Chile's Darwin frog (Rhinoderma rufum) and the Betic Midwife Toad

A larva (Latin; plural larvae) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. Larva is Latin for "ghost."

The larva's appearance is generally very different from the adult form (e.g. caterpillars and butterflies), and a larva often has unique structures and larval organs that do not occur in the adult form. A larva's diet can be considerably different from its adult form.

Larvae are frequently adapted to environments separate from adults. For example, some larvae such as tadpoles live exclusively in aquatic environments, but as adults can live outside water as frogs. By living in distinct environments, larvae may be given shelter from predators and reduce competition for resources with the adult population.

Animals in the larval stage will consume food to fuel their transition into the adult form. Some species such as barnacles are immobile as adults, and use their mobile larvae form to distribute themselves.

The larvae of some species can become pubescent and not further develop into the adult form (for example, in some newts). This is a type of neoteny.

Eurosta solidaginis Goldenrod Gall Fly larva

It is a misunderstanding that the larval form always reflects the group's evolutionary history. It could be the case, but often the larval stage has evolved secondarily, as in insects. In these cases the larval form might differ more from the group's common origin than the adult form.

Names of various kinds of larvae:

Metamorphosis is a biological process by which an animal physically develops after birth or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and differentiation. Some insects, amphibians, mollusks, crustaceans, Cnidarians, echinoderms and tunicates undergo metamorphosis, which is usually accompanied by a change of habitat or behavior.

Scientific usage of the term is exclusive, and is not applied to general aspects of cell growth, including rapid growth spurts. References to "metamorphosis" in mammals are imprecise and only colloquial, but historically idealist ideas of transformation and monadology, as in Goethe's Metamorphosis of Plants, influenced the development of ideas of evolution.

Etymology

The word "metamorphosis" derives from Greek μεταμόρφωσις, "transformation, transforming"^[1], from μετα- (meta-), "change" + μορφή (morphe) "form"^[2].

Insect metamorphosis

Metamorphosis usually proceeds in distinct stages, starting with larva or nymph, optionally passing through pupa, and ending as adult or imago. There are two main types of metamorphosis in insects, hemimetabolism and holometabolism.

Incomplete metamorphosis in the grasshopper with different instar nymphs

The immature stages of a species that metamorphosises are usually called larvae, and in these stages may grow quite quickly. But in the complex metamorphosis of many insect species, only the first stage is called a larva and sometimes even that bears a different name; the distinction depends on the nature of the metamorphosis.

In hemimetabolism, the development of larva often proceeds in repeated stages of growth and ecdysis (moulting); these stages are called instars. The juvenile forms closely resemble adults, but are smaller and, if the adult has wings, lack wings. This process is also known as "simple", "gradual" or "incomplete" metamorphosis. The differences between juveniles in different instars are small, often just differences in body proportions and the number of segments.

In holometabolism, the larvae differ markedly from the adults. Insects which undergo holometabolism pass through a larval stage, then enter an inactive state called pupa, or chrysalis, and finally emerge as adults. Holometabolism is also known as "complete" and "complex" metamorphosis. Whilst inside the pupa, the insect will excrete digestive juices, to destroy much of the larva's body, leaving a few cells intact. The remaining cells will begin the growth of the adult, using the nutrients from the broken down larva. This process of cell death is called histolysis, and cell regrowth histogenesis.

Whether the insect spends more time in its adult stage or in its juvenile form depends on the species. Notable examples are the mayfly, whose non-eating, adult stage lives for one day, and the cicada, whose juvenile stage live underground for 13 or 17 years. These species have incomplete metamorphosis. Typically, though not exclusively, species in which the adult form outlives the juvenile form undergo complex metamorphosis.

Many observations have indicated that programmed cell death plays a considerable role during physiological processes of multicellular organisms, particularly during embryogenesis and metamorphosis.

Pieris rapae larva

Pieris rapae pupa

Pieris rapae pupa, ready to hatch.

A Pieris rapae adult

Hormonal control

Insect growth and metamorphosis are controlled by hormones synthesized by endocrine glands near the front of the body.

neurosecretory cells of an insect's brain secrete a hormone, the prothoracicotropic hormone that activates prothoracic glands, which secrete a second hormone, usually Ecdysone (a steroid), that induces metamorphosis.

Moreover, the corpora allata, a retrocerebral organ produces the juvenile hormone, whose effect is to prevent the development of adult characteristics while allowing ecdysis. Therefore, the insect is subject to a series of molting, controlled by Ecdysone, until the production of juvenile hormone ceases and metamorphosis occurs.

Amphibian metamorphosis

Just before metamorphosis, only 24 hours are needed to reach the stage in the next picture

Almost functional common frog with some remains of the gill sac and a not fully developed jaw

In typical amphibian development the eggs are laid in water and the larvae are adapted to an aquatic lifestyle. Both frogs, toads, and newts hatch from the egg as larvae with external gills. After that the newt larvae are starting a predatory lifestyle, the tadpoles are mostly scraping off food from surfaces with their horny tooth ridges. Metamorphosis in amphibians is regulated by thyroxin concentration in the blood, that stimulates metamorphosis and prolactin that counteracts its effect. The specific events are dependent of the threshold values for different tissues. Because most of the embryonic development is outside the parental body the development is subject to a lot of adaptations due to specific ecological circumstances. For this reason tadpoles can have horny ridges for teeth, whiskers and fins. They also make use of the lateral line organ. After metamorphosis these organs become redundant and will be resorbed by controlled cell death called apoptosis. The amount of adaptations to specific ecological circumstances is amazing and there are still discoveries being made.

Frogs and toads

With frogs and toads the external gills of the newly hatched tadpole are covered in a few days with a gill sac and lungs are quickly formed. Under the gill sac the front legs are formed and the hindlegs are also visible a few days later. Then there usually is a longer stage where the tadpole is growing on a vegetarian diet. The tadpoles use a spiral shaped relatively long gut to digest that diet.

After that, very quick changes in the body can be observed when the lifestyle of the frog changes completely. The trunk shaped mouth with horny tooth ridges is resorbed together with the spiral gut. The animal develops a big jaw, the gills disappear as well as the gill sac. The eyes grow at a very fast rate as well as the legs, a tongue is formed and all this is completed with the associated changes in the neural networks (development of stereoscopic vision, loss of the lateral line system etc.) All of this can happen in about a day, so it is truly a metamorphosis. A few days later also the tail is reabsorbed, due to the higher thyroxin concentrations required for tail resorption.

Newts

The large external gills of the crested newt

In newts there is not really such a thing as metamorphosis, because the larvae start feeding as predators always and continue to do so in the adult stage. The gills of newts are never covered by a gill sac and will be resorbed only just before the animal leaves the water. Just like in tadpoles the lungs are functional very soon also, but they don't make as much use of them as tadpoles do. Newts often have an aquatic phase in spring and summer and a land phase in winter. For adaptation to a water phase prolactin is the required hormone and for adaptations to the land phase thyroxin. The external gills do not return in subsequent aquatic phases because they are completely absorbed upon leaving the water for the first time.

Metamorphosis in fish and invertebrate aquatic animals

Little known is that also fish, i.e. bony fish, undergo metamorphosis. Fish metamorphosis is typically under strong control by thyroid hormone. Examples include the agnatha, salmon, and lamprey, which must change from a freshwater to saltwater lifestyle (diadromous). Additionally, the flatfish begins its life bilaterally symmetrical, and one eye must move to join the other side of the fish in its adult form.

Amphibians (class Amphibia, from Amphi- meaning "on both sides" and -bios meaning "life"), such as frogs, toads, salamanders, newts, and caecilians, are ectothermic (or cold-blooded) animals that metamorphose from a juvenile water-breathing form, either to an adult air-breathing form, or to a paedomorph that retains some juvenile characteristics. Proteidae (mudpuppies and waterdogs) are good examples of paedomorphic species. Though amphibians typically have four limbs, the caecilians are notable for being limbless. Unlike other land vertebrates (amniotes), most amphibians lay eggs in water. Amphibians are superficially similar to reptiles.

Amphibians are ecological indicators, and in recent decades there has been a dramatic decline in amphibian populations around the globe. Many species are now threatened or extinct.

Amphibians evolved in the Devonian Period and were top predators in the Carboniferous and Permian Periods, but many lineages were wiped out during the Permian–Triassic extinction. One group, the metoposaurs, remained important predators during the Triassic, but as the world became drier during the Early Jurassic they died out, leaving a handful of relict temnospondyls like Koolasuchus and the modern orders of Lissamphibia.

Etymology

Amphibian is derived from the Ancient Greek term ἀμφίβιος amphíbios which means both kinds of life, amphi meaning “both” and bio meaning life. The term was initially used for all kinds of combined natures. Eventually it was used to refer to animals that live both in the water and on land.^[1]

Evolutionary history

The first major groups of amphibians developed in the Devonian Period from fish similar to the modern coelacanth and lungfish which had evolved multi-jointed leg-like fins that enabled them to crawl along the sea bottom. These amphibians were as much as one to five meters in length. However, amphibians never developed the ability to live their entire lives on land, having to return to water to lay their shell-less eggs.

In the Carboniferous Period, the amphibians moved up in the food chain and began to occupy the ecological position currently occupied by crocodiles. These amphibians were notable for eating the mega insects on land and many types of fishes in the water. During the Triassic Period, the better land-adapted proto-crocodiles began to compete with amphibians, leading to their reduction in size and importance in the biosphere.

Taxonomic history

Traditionally, amphibians have included all tetrapod vertebrates that are not amniotes. They are divided into three subclasses, of which two are only known as extinct subclasses:

• Subclass Labyrinthodontia† (diverse Paleozoic and early Mesozoic group)
• Subclass Lepospondyli† (small Paleozoic group, sometimes included in the Labyrinthodontia)
• Subclass Lissamphibia (frogs, toads, salamanders, newts, etc.)

Of these only the last subclass includes recent species.

With the phylogenetic classification Labyrinthodontia has been discarded as it is a paraphyletic group without unique defining features apart from shared primitive characteristics. Classification varies according to the preferred phylogeny of the author, whether they use a stem-based or node-based classification. Generally amphibians are defined as the group that includes the common ancestors of all living amphibians (frogs, salamanders and caecilians) and all their descendants. This may also include extinct groups like the temnospondyls (traditionally placed in the subclass “Labyrinthodontia”), and the Lepospondyls. This means that cladistic nomenklature list a large number of basal Devonian and Carboniferous tetrapod groups, undoubtedly were “amphibians” in biology, that are formally placed in Amphibia in Linnaean taxonomy, but not in cladistic taxonomy.

All recent amphibians are included in the subclass Lissamphibia, superorder Salientia, which is usually considered a clade (which means that it is thought that they evolved from a common ancestor apart from other extinct groups), although it has also been suggested that salamanders arose separately from a temnospondyl-like ancestor.^[2]

Authorities also disagree on whether Salientia is a Superorder that includes the order Anura, or whether Anura is a sub-order of the order Salientia. Practical considerations seem to favor using the former arrangement now. The Lissamphibia, superorder Salientia, are traditionally divided into three orders, but an extinct salamander-like family, the Albanerpetontidae, is now considered part of the Lissamphibia, besides the superorder Salientia. Furthermore, Salientia includes all three recent orders plus a single Triassic proto-frog, Triadobatrachus.

Class Amphibia

• Subclass Lissamphibia
  • • Family Albanerpetontidae — Jurassic to Miocene (extinct)
  • Superorder Salientia
    • Genus Triadobatrachus — Triassic (extinct)
    • Order Anura (frogs and toads): Jurassic to recent — 5,602 recent species in 48 families
    • Order Caudata or Urodela (salamanders, newts): Jurassic to recent — 571 recent species in 9 families
    • Order Gymnophiona or Apoda (caecilians): Jurassic to recent — 174 recent species in 3 families

The actual number of species partly also depends on the taxonomic classification followed, the two most common classifications being the classification of the website AmphibiaWeb, University of California (Berkeley) and the classification by herpetologist Darrel Frost and The American Museum of Natural History, available as the online reference database Amphibian Species of the World.^[3] The numbers of species cited above follow Frost.

Respiration

The lungs in amphibians are primitive compared to that of the amniotes, possessing few internal septa, large alveoli and therefore a slow diffusion rate of oxygen into the blood. Ventilation is accomplished by buccal pumping. However, most amphibians are able to exchange gasses with the water or air via their skin. To enable sufficient cutaneous respiration, the surface of their highly vascularized skin must remain moist in order for the oxygen to diffuse at a sufficient rate. Because oxygen concentration in the water increases at both low temperatures and high flow rates, aquatic amphibians in these situations can rely primarily on cutaneous respiration, as in the Titicaca water frog or hellbender salamanders. In air, where oxygen is more concentrated, some small species can rely solely on cutaneous gas exchange, most famously the plethodontid salamanders which have neither lungs nor gills. Many aquatic salamanders and all tadpoles have gills in their larval stage, with some (such as the axolotl) retaining gills as aquatic adults.

Reproductive system

Caecilian from the San Antonio zoo

For the purpose of reproduction most amphibians require fresh water. A few (e.g. Fejervarya raja) can inhabit brackish water and even survive (though not thrive) in seawater, but there are no true marine amphibians. Several hundred frog species in adaptive radiations (e.g., Eleutherodactylus, the Pacific Platymantines, the Australo-Papuan microhylids, and many other tropical frogs), however, do not need any water for breeding in the wild. They reproduce via direct development, an ecological and evolutionary adaptation that has allowed them to be completely independent from free-standing water. Almost all of these frogs live in wet tropical rainforests and their eggs hatch directly into miniature versions of the adult, passing through the tadpole stage within the egg. Several species have also adapted to arid and semi-arid environments, but most of them still need water to lay their eggs. Symbiosis with single celled algae that lives in the jelly-like layer of the eggs has evolved several times. The larvae (tadpoles or polliwogs) breathe with exterior gills. After hatching, they start to transform gradually into the adult's appearance. This process is called metamorphosis. Typically, the animals then leave the water and become terrestrial adults, but there are many interesting exceptions to this general way of reproduction.

The most obvious part of the amphibian metamorphosis is the formation of four legs in order to support the body on land. But there are several other changes:

• The gills are replaced by other respiratory organs, i.e., lungs.
• The skin changes and develops glands to avoid dehydration.
• The eyes develop eyelids and adapt to vision outside the water.
• An eardrum is developed to lock the middle ear.
• In frogs and toads, the tail disappears.

Conservation

The Golden Toad of Monteverde, Costa Rica was among the first casualties of amphibian declines. Formerly abundant, it was last seen in 1989.

Dramatic declines in amphibian populations, including population crashes and mass localized extinction, have been noted in the past two decades from locations all over the world, and amphibian declines are thus perceived as one of the most critical threats to global biodiversity. A number of causes are believed to be involved, including habitat destruction and modification, over-exploitation, pollution, introduced species, climate change, endocrine-disrupting pollutants, destruction of the ozone layer (ultraviolet radiation has shown to be especially damaging to the skin, eyes, and eggs of amphibians), and diseases like chytridiomycosis. However, many of the causes of amphibian declines are still poorly understood, and are a topic of ongoing discussion. A global strategy to stem the crisis has been released in the form of the Amphibian Conservation Action Plan (available at http://www.amphibians.org). Developed by over 80 leading experts in the field, this call to action details what would be required to curtail amphibian declines and extinctions over the next 5 years - and how much this would cost. The Amphibian Specialist Group of the World Conservation Union (IUCN) is spearheading efforts to implement a comprehensive global strategy for amphibian conservation.

On January 21, 2008, Evolutionarily Distinct and Globally Endangered (EDGE), as given by chief Helen Meredith, identified nature's most endangered species: "The EDGE amphibians are amongst the most remarkable and unusual species on the planet and yet an alarming 85% of the top 100 are receiving little or no conservation attention." The top 10 endangered species (in the List of endangered animal species) include: the Chinese giant salamander, a distant relative of the newt, the tiny Gardiner's Seychelles, the limbless Sagalla caecilian, South African ghost frogs, lungless Mexican salamanders, the Malagasy rainbow frog, Chile's Darwin frog (Rhinoderma rufum) and the Betic Midwife Toad

The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in females are homologous to testes in males, in that they are both gonads and endocrine glands.

Human anatomy

Ovaries are oval shaped and, in the human, measure approximately 3 cm x 1.5 cm x 1.5 cm (about the size of a Greek olive). The ovary (for a given side) is located in the lateral wall of the pelvis in a region called the ovarian fossa. The fossa usually lies beneath the external iliac artery and in front of the ureter and the internal iliac artery.

The ovaries aren't attached to the fallopian tubes but to the outer layer of the uterus via the ovarian ligaments. Usually each ovary takes turns releasing eggs every month; however, if there was a case where one ovary was absent or dysfunctional then the other ovary would continue providing eggs to be released.

Hormones

Ovaries secrete both estrogen and progesterone. Estrogen is responsible for the appearance of secondary sex characteristics of females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state. Progesterone functions with estrogen by promoting cyclic changes in the endometrium (it prepares the endometrium for pregnancy), as well as by helping maintain the endometrium in a healthy state during pregnancy.

 Ligaments

In the human the paired ovaries lie within the pelvic cavity, on either side of the uterus, to which they are attached via a fibrous cord called the ovarian ligament. The ovaries are uncovered in the peritoneal cavity but are tethered to the body wall via the suspensory ligament of the ovary. The part of the broad ligament of the uterus that covers the ovary is known as the mesovarium. Thus, the ovary is the only organ in the human body which is totally invaginated into the peritonium, making it the only interperitoneal organ (not to be confused with intraperitoneal).

Extremities

There are two extremities to the ovary:

• The end to which the uterine tube attach is called the tubal extremity.
• The other extremity is called the uterine extremity. It points downward, and it is attached to the uterus via the ovarian ligament.

Histology

Cell Types

• Follicular cells flat epithelial cells that originate from surface epithelium covering the ovary
• granulosa cells - surrounding follicular cells have change from flat to cuboidal and proliferated to produce a stratified epithelium
• Gametes^[1]

Section of the ovary of a newly born child. Germinal epithelium is seen at top. Primitive ova are seen in their cell-nests. The Genital cord or genital ridge is still discernible in this young child. A blood vessel and an ovarian follicle is also seen

• The outermost layer is called the ovarian surface epithelium (previously known as the germinal epithelium).
• The tunica albuginea covers the cortex.
• The ovarian cortex consists of ovarian follicles and stroma in between them. Included in the follicles are the cumulus oophorus, membrana granulosa (and the granulosa cells inside it), corona radiata, zona pellucida, and primary oocyte. The zona pellucida, theca of follicle, antrum and liquor folliculi are also contained in the follicle. Also in the cortex is the corpus luteum derived from the follicles.
• The innermost layer is the ovarian medulla. It can be hard to distinguish between the cortex and medulla, but follicles are usually not found in the medulla.

In other animals

Ovaries of some kind are found in the female reproductive system of many animals that employ sexual reproduction, including invertebrates. However, they develop in a very different way in most invertebrates than they do in vertebrates, and are not truly homologous.^[2]

Many of the features found in human ovaries are common to all vertebrates, including the presence of follicular cells, tunica albuginea, and so on. However, many species produce a far greater number of eggs during their lifetime than do humans, so that, in fish and amphibians, there may be hundreds, or even millions of fertile eggs present in the ovary at any given time. In these species, fresh eggs may be developing from the germinal epithelium throughout life. Corpora lutea are found only in mammals, and in some elasmobranch fish; in other species, the remnants of the follicle are quickly resorbed by the ovary. In birds, reptiles, and monotremes, the egg is relatively large, filling the follicle, and distorting the shape of the ovary at maturity.^[2]

Amphibians and reptiles have no ovarian medulla; the central part of the ovary is a hollow, lymph-filled space. The ovary of teleosts is also often hollow, but in this case, the eggs are shed into the cavity, which opens into the oviduct.^[2]

Although most normal female vertebrates have two ovaries, this is not the case in all species. In birds and platypuses, the right ovary never matures, so that only the left is functional. In some elasmobranchs, the reverse is true, with only the right ovary fully developing. In the primitive jawless fish, and some teleosts, there is only one ovary, formed by the fusion of the paired organs in the embryo.^[2]

Cryopreservation

Cryopreservation of ovarian tissue, often called Ovarian Tissue Cryopreservation, is of interest to women who want to preserve their reproductive function beyond the natural limit, or whose reproductive potential is threatened by cancer therapy,^[3] for example in hematologic malignancies or breast cancer.^[4] The procedure is to take a part of the ovary and carry out slow freezing before storing it in liquid nitrogen whilst therapy is undertaken. Tissue can then be thawed and implanted near the fallopian, either orthotopic (on the natural location) or heterotopic (on the abdominal wall),^[4] where it starts to produce new eggs, allowing normal conception to take place. ^[5] A study of 60 procedures concluded that ovarian tissue harvesting appears to be safe.^[4] The ovarian tissue may also be transplanted into mice that are immunocompromised (SCID mice) to avoid graft rejection, and tissue can be harvested later when mature follicles have developed

A thrombus (Greek θρόμβος), or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is normal in cases of injury, but pathologic in instances of thrombosis.

Pathophysiology

Specifically, a thrombus is the inappropriate activation of the hemostatic process in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut-off (termed an occlusive thrombus) resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is termed as an embolus.

Some of the conditions which elevate risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity (see deep venous thrombosis), and genetic or disease-related deficiencies in the blood's clotting abilities.

Treatment

Blood clot prevention and treatment reduces the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are often used to inhibit the formation and growth of existing thrombi; the former binds to and activates the enzyme inhibitor antithrombin III, while the latter inhibits vitamin K epoxide reductase, an enzyme needed to synthesize mature clotting factors.

Presentation

Virchow's triad describes the pathogenesis of thrombus formation:

1. Endothelial injury (injury to the endothelial cells that line enclosed spaces of the body, such as the inside of blood vessels) (e.g. trauma, atheroma)
2. Abnormal blood flow (loss of laminar flow resulting from stasis in veins or turbulence in arteries) (e.g. valvulitis, aneurysm)
3. Hypercoagulability (e.g. leukaemia, Factor V mutation (Leiden))

Disseminated intravascular coagulation (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of fibrinolysis using all of the body's available platelets and clotting factors. The end result is hemorrhaging and ischaemic necrosis of tissue/organs. Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. DIC may also be seen in pregnant females. Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, platelets and heparin to prevent further thrombi formation.

Prognosis

Thrombus formation can have one of four outcomes: propagation, embolization, dissolution or organization and recanalization. ^[1]

1. Propagation of a thrombus occurs towards the direction of the heart. This means that it is anterograde in veins or retrograde in arteries.
2. Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile. A venous emboli (most likely from deep venous thrombosis in the lower extremities) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery resulting in a pulmonary embolism. On the other hand, arterial thrombosis resulting from hypertension or atherosclerosis can become mobile and the resulting emboli can occlude any artery or arteriole downstream of the thrombus formation. This means that cerebral stroke, myocardial infarction, or any other organ can be affected.
3. Dissolution occurs when fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by drugs (for example after occlusion of a coronary artery). The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed.
4. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. Recanalization provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue.

Platelets, or thrombocytes (from Greek θρόμβος — «clot» and κύτος — «cell»), are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2-3 µm in diameter^[1], which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis and are a natural source of growth factors. They circulate in the blood of mammals and are involved in hemostasis, leading to the formation of blood clots.

If the number of platelets is too low, excessive bleeding can occur. However, if the number of platelets is too high, blood clots can form (thrombosis), which may obstruct blood vessels and result in such events as a stroke, myocardial infarction, pulmonary embolism or the blockage of blood vessels to other parts of the body, such as the extremities of the arms or legs.  An abnormality or disease of the platelets is called a thrombocytopathy^[2], which could be either a low number of platelets (thrombocytopenia), a decrease in function of platelets (thrombasthenia), or an increase in the number of platelets (thrombocytosis). There are disorders that reduce the number of platelets, such as heparin-induced thrombocytopenia (HIT) or thrombotic thrombocytopenic purpura (TTP) that typically cause thromboses, or clots, instead of bleeding.

Platelets release a multitude of growth factors including Platelet-derived growth factor (PDGF), a potent chemotactic agent, and TGF beta, which stimulates the deposition of extracellular matrix.  Both of these growth factors have been shown to play a significant role in the repair and regeneration of connective tissues.  Other healing-associated growth factors produced by platelets include basic fibroblast growth factor, insulin-like growth factor 1, platelet-derived epidermal growth factor, and vascular endothelial growth factor.  Local application of these factors in increased concentrations through Platelet-rich plasma (PRP) has been used as an adjunct to wound healing for several decades

Kinetics

Blood cell lineage

• Platelets are produced in blood cell formation (thrombopoiesis) in bone marrow, by budding off from megakaryocytes.
• The physiological range for platelets is 150-400 x 10⁹ per liter.
• Around 1 x 10¹¹ platelets are produced each day by an average healthy adult.
• The lifespan of circulating platelets is 5 to 9 days.
• Megakaryocyte and platelet production is regulated by thrombopoietin, a hormone usually produced by the liver and kidneys.
• Each megakaryocyte produces between 5,000 and 10,000 platelets.
• Old platelets are destroyed by phagocytosis in the spleen and by Kupffer cells in the liver.
• A reserve of platelets are stored in the spleen and are released when needed by sympathetically-induced splenic contraction.

Thrombus formation

Aggregation of platelets. Platelet rich human blood plasma (left vial) is a turbid liquid. Upon addition of ADP, platelets are activated and start to aggregate, forming white flakes (right vial).

The function of platelets is the maintenance of hemostasis.  This is achieved primarily by the formation of thrombi, when damage to the endothelium of blood vessels occurs. On the converse, thrombus formation must be inhibited at times when there is no damage to the endothelium.

Activation

The inner surface of blood vessels is lined with a thin layer of endothelial cells that, in normal hemostasis, acts to inhibit platelet activation by producing nitric oxide, endothelial-ADPase, and PGI₂.  Endothelial-ADPase clears away the platelet activator, ADP.

Endothelial cells produce a protein called von Willebrand factor (vWF), a cell adhesion ligand, which helps endothelial cells adhere to collagen in the basement membrane. Under physiological conditions, collagen is not exposed to the bloodstream. vWF is secreted constitutively into the plasma by the endothelial cells, and is stored in granules within the endothelial cell and in platelets.

When the endothelial layer is injured, collagen, vWF and tissue factor from the subendothelium is exposed to the bloodstream. When the platelets contact collagen or vWF, they are activated (eg. to clump together). They are also activated by thrombin (formed with the help of tissue factor). They can also be activated by a negatively-charged surface, such as glass.

Platelet activation further results in the scramblase-mediated transport of negatively-charged phospholipids to the platelet surface.  These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase complexes. Calcium ions are essential for binding of these coagulation factors.

Shape change

Scanning electron micrograph of blood cells. From left to right: human erythrocyte, activated thrombocyte (platelet), leukocyte.

Activated platelets change in shape to become more spherical, and pseudopods form on their surface.  Thus they assume a stellate shape.

Granule secretion

Platelets contain alpha and dense granules.  Activated platelets excrete the contents of these granules into their canalicular systems and into surrounding blood.  There are three types of granules:

• delta granules (containing ADP or ATP, calcium, and serotonin)
• lamda granules - similar to lysosomes and contain several hydrolytic enzymes.
• α-granules (containing platelet factor 4, transforming growth factor-β1, platelet-derived growth factor, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII).

Thromboxane A2 synthesis

Platelet activation initiates the arachidonic acid pathway to produce TXA₂.  TXA₂ is involved in activating other platelets and its formation is inhibited by COX inhibitors, such as aspirin.

Adhesion and aggregation

Platelets aggregate, or clump together, using fibrinogen and vWF as a connecting agent.  The most abundant platelet aggregation receptor is glycoprotein IIb/IIIa (gpIIb/IIIa); this is a calcium-dependent receptor for fibrinogen, fibronectin, vitronectin, thrombospondin, and von Willebrand factor (vWF).  Other receptors include GPIb-V-IX complex (vWF) and GPVI (collagen).

Activated platelets will adhere, via glycoprotein (GP) Ia, to the collagen that is exposed by endothelial damage.  Aggregation and adhesion act together to form the platelet plug.  Myosin and actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug.

Platelet aggregation is stimulated by ADP, thromboxane, and α2 receptor-activation, but inhibited by other inflammatory products like PGI2 and PGD2.  Platelet aggregation is enhanced by exogenous administration of anabolic steroids.

Wound repair

The blood clot is only a temporary solution to stop bleeding; vessel repair is therefore needed. The aggregated platelets help this process by secreting chemicals that promote the invasion of fibroblasts from surrounding connective tissue into the wounded area to form a scar. The obstructing clot is slowly dissolved by the fibrinolytic enzyme, plasmin, and the platelets are cleared by phagocytosis.

Other functions

• Clot retraction
• Pro-coagulation
• Inflammation
• Cytokine signalling
• Phagocytosis^[10]

Cytokine signaling

In addition to being the chief cellular effector of hemostasis, platelets are rapidly deployed to sites of injury or infection, and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines, and other inflammatory mediators^{[11] [12] [13] [14]}.  Platelets also secrete platelet-derived growth factor (PDGF).

Role in disease

High and low counts

A normal platelet count in a healthy individual is between 150,000 and 450,000 per μl (microlitre) of blood (150–450 x 10⁹/L)^[15].  Ninety-five percent of healthy people will have platelet counts in this range.  Some will have statistically abnormal platelet counts while having no demonstrable abnormality.  However, if it is either very low or very high, the likelihood of an abnormality being present is higher.

Both thrombocytopenia and thrombocytosis may present with coagulation problems.  In general, low platelet counts increase bleeding risks; however there are exceptions. For example, immune heparin-induced thrombocytopenia and thrombocytosis (high counts) may lead to thrombosis, although this is mainly when the elevated count is due to myeloproliferative disorder.

Low platelet counts are, in general, not corrected by transfusion unless the patient is bleeding or the count has fallen below 5 x 10⁹/L.  Transfusion is contraindicated in thrombotic thrombocytopenic purpura (TTP), as it fuels the coagulopathy.  In patients undergoing surgery, a level below 50 x 10⁹/L is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as epidurals are avoided for levels below 80-100.

Normal platelet counts are not a guarantee of adequate function.  In some states, the platelets, while being adequate in number, are dysfunctional.  For instance, aspirin irreversibly disrupts platelet function by inhibiting cyclooxygenase-1 (COX1), and hence normal hemostasis.  The resulting platelets are unable to produce new cyclooxygenase because they have no DNA.  Normal platelet function will not return until the use of aspirin has ceased and enough of the affected platelets have been replaced by new ones, which can take over a week.  Ibuprofen, another NSAID, does not have such a long duration effect, with platelet function usually returning within 24 hours^[16], and taking ibuprofen before aspirin will prevent the irreversible effects of aspirin^[17].  Uremia, a consequence of renal failure, leads to platelet dysfunction that may be ameliorated by the administration of desmopressin.

Medications

Oral agents, often used to alter/suppress platelet function:

• aspirin
• clopidogrel
• cilostazol
• ticlopidine

Intravenous agents, often used to alter/suppress platelet function:

• abciximab
• eptifibatide
• tirofiban

Diseases

Disorders leading to a reduced platelet count:

• Thrombocytopenia
  • Idiopathic thrombocytopenic purpura - also known as immune thrombocytopenic purpura (ITP)
  • Thrombotic thrombocytopenic purpura
  • Drug-induced thrombocytopenic purpura (for example heparin-induced thrombocytopenia (HIT))
• Gaucher's disease
• Aplastic anemia

Alloimmune disorders

• Fetomaternal alloimmune thrombocytopenia
• Some transfusion reactions

Disorders leading to platelet dysfunction or reduced count:

• HELLP syndrome
• Hemolytic-uremic syndrome
• Chemotherapy
• Dengue

Disorders featuring an elevated count:

• Thrombocytosis, including essential thrombocytosis (elevated counts, either reactive or as an expression of myeloproliferative disease); may feature dysfunctional platelets

Disorders of platelet adhesion or aggregation:

• Bernard-Soulier syndrome
• Glanzmann's thrombasthenia
• Scott's syndrome
• von Willebrand disease
• Hermansky-Pudlak Syndrome
• Gray platelet syndrome

Disorders of platelet metabolism

• Decreased cyclooxygenase activity, induced or congenital
• Storage pool defects, acquired or congenital

Disorders that indirectly compromise platelet function:

• Haemophilia

Disorders in which platelets play a key role:

• Atherosclerosis
• Coronary artery disease, CAD and myocardial infarction, MI
• Cerebrovascular disease and Stroke, CVA (cerebrovascular accident)
• Peripheral artery occlusive disease (PAOD)
• Cancer ^[18]

Condition	Prothrombin time	Partial thromboplastin time	Bleeding time	Platelet count
Vitamin K deficiency or Warfarin	prolonged	prolonged	unaffected	unaffected
Disseminated intravascular coagulation	prolonged	prolonged	prolonged	decreased
Von Willebrand disease	unaffected	prolonged	prolonged	unaffected
Haemophilia	unaffected	prolonged	unaffected	unaffected
Aspirin	unaffected	unaffected	prolonged	unaffected
Thrombocytopenia	unaffected	unaffected	prolonged	decreased
Early Liver failure	prolonged	unaffected	unaffected	unaffected
End-stage Liver failure	prolonged	prolonged	prolonged	decreased
Uremia	unaffected	unaffected	prolonged	unaffected
Congenital afibrinogenemia	prolonged	prolonged	prolonged	unaffected
Factor V deficiency	prolonged	prolonged	unaffected	unaffected
Factor X deficiency as seen in amyloid purpura	prolonged	prolonged	unaffected	unaffected
Glanzmann's thrombasthenia	unaffected	unaffected	prolonged	unaffected
Bernard-Soulier syndrome	unaffected	unaffected	prolonged	decreased

Discovery

Brewer^[19] traced the history of the discovery of the platelet.  Although red blood cells had been known since van Leeuwenhoek (1632-1723), it was the German anatomist Max Schultze (1825-1874) who first offered a description of the platelet in his newly-founded journal Archiv für mikroscopische Anatomie^[20].  He describes "spherules" to be much smaller than red blood cells that are occasionally clumped and may participate in collections of fibrous material.  He recommends further study of the findings.

Giulio Bizzozero (1846-1901), building on Schultze's findings, used "living circulation" to study blood cells of amphibians microscopically in vivo.  He is especially noted for discovering that platelets clump at the site of blood vessel injury, a process that precedes the formation of a blood clot.  This observation confirmed the role of platelets in coagulation^[21].

In transfusion medicine

Platelets are either isolated from collected units of whole blood and pooled to make a therapeutic dose or collected by apheresis, sometimes concurrently with plasma or red blood cells.  The industry standard is for platelets to be tested for bacteria before transfusion to avoid septic reactions, which can be fatal.

Pooled whole-blood platelets, sometimes called "random" platelets, are made by taking a unit of whole blood that has not been cooled and placing it into a large centrifuge in what is referred to as a "soft spin."  This splits the blood into three layers: the plasma, a "buffy coat" layer, which includes the platelets, and the white blood cells.  These are expressed into different bags for storage.

Apheresis platelets are collected using a mechanical device that draws blood from the donor and centrifuges the collected blood to separate out the platelets and other components to be collected.  The remaining blood is returned to the donor.  The advantage to this method is that a single donation provides at least one therapeutic dose, as opposed to the multiple donations for whole-blood platelets.  This means that a recipient is not exposed to as many different donors and has less risk of transfusion-transmitted disease and other complications.  Sometimes a person such as a cancer patient that requires routine transfusions of platelets will receive repeated donations from a specific donor to further minimize the risk.

Platelets are not cross-matched unless they contain a significant amount of red blood cells (RBCs), which results in a reddish-orange color to the product.  This is usually associated with whole-blood platelets, as apheresis methods are more efficient than "soft spin" centrifugation at isolating the specific components of blood.  An effort is usually made to issue type specific platelets, but this is not as critical as it is with RBCs.

Platelets collected by either method have a very short shelf life, typically five or seven days depending on the system used.  This results in frequent problems with short supply, as testing the donations often requires up to a full day.  Since there are no effective preservative solutions for platelets, they lose potency quickly and are best when fresh.

Platelets, either apheresis or random-donor platelets, can be processed through a volume reduction process.  In this process, the platelets are spun in a centrifuge and the excess plasma is removed, leaving 10 to 100 ml of platelet concentrate.  Volume-reduced platelets are normally transfused only to neonatal and pediatric patients when a large volume of plasma could overload the child's small circulatory system.  The lower volume of plasma also reduces the chances of an adverse transfusion reaction to plasma proteins.^[22]  Volume reduced platelets have a shelf life of only four hours.

The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume fraction (EVF) is the proportion of blood volume that is occupied by red blood cells. It is normally about 48% for men and 38% for women.^[1] It is considered an integral part of a person's complete blood count results, along with hemoglobin concentration, white blood cell count, and platelet count.

In mammals, hematocrit is independent of body size.

The term "hematocrit" (British English: haematocrit) was coined in 1903. Its roots stem from the Greek words hema (Gr αἷμα)—blood, and krites (Gr κριτής), judge—meaning to gauge or judge the blood.

Measurement methods

Packed cell volume diagram

The packed cell volume (PCV) can be determined by centrifuging heparinized blood in a capillary tube (also known as a microhematocrit tube) at 10,000 RPM for five minutes.^[2] This separates the blood into layers. The volume of packed red blood cells divided by the total volume of the blood sample gives the PCV. Because a tube is used, this can be calculated by measuring the lengths of the layers.

With modern lab equipment, the hematocrit is calculated by an automated analyzer and not directly measured. It is determined by multiplying the red cell count by the mean cell volume. The hematocrit is slightly more accurate as the PCV includes small amounts of blood plasma trapped between the red cells. An estimated hematocrit as a percentage may be derived by tripling the hemoglobin concentration in g/dL and dropping the units.^[3] The hemoglobin level is the measure used by blood banks.^{[clarification needed][citation needed]}

There have been cases in which the blood for testing was inadvertently drawn proximal to an intravenous line that was infusing packed red cells or fluids. In these situations, the hemoglobin level in the blood sample will not be the true level for the patient because the sample would contain a large amount of the infused material rather than what is diluted into the circulating whole blood. That is, if packed red cells are being supplied, the sample will contain a large amount of those cells and the hematocrit will be artificially very high. On the converse, if saline or other fluids are being supplied, the blood sample would be diluted and the hematocrit will be artificially low.

Elevated hematocrit

In cases of dengue fever, a high hematocrit is a danger sign of an increased risk of dengue shock syndrome.

Polycythemia vera (PV), a myeloproliferative disorder in which the bone marrow produces excessive numbers of red cells, is associated with elevated hematocrit.

Chronic obstructive pulmonary disease (COPD) and other pulmonary conditions associated with hypoxia may elicit an increased production of red blood cells. This increase is mediated by the increased levels of erythropoietin by the kidneys in response to hypoxia.

Professional athletes' hematocrit levels are measured as part of tests for blood doping or Erythropoietin (EPO) use; the level of hematocrit in a blood sample is compared with the long-term level for that athlete (to allow for individual variations in hematocrit level), and against an absolute permitted maximum (which is based on maximum expected levels within the population, and the hematocrit level that causes increased risk of blood clots resulting in strokes or heart attacks).

Anabolic Androgenic Steroid (AAS) use can also increase the amount of RBCs and, therefore, impact the hematocrit, in particular the compounds boldenone and oxymethelone.

If a patient is dehydrated, the hematocrit may be elevated.

Lowered hematocrit

Lowered hematocrit can imply significant hemorrhage.

The mean corpuscular volume (MCV) and the red cell distribution width (RDW) can be quite helpful in evaluating a lower-than-normal hematocrit, because it can help the clinician determine whether blood loss is chronic or acute. The MCV is the size of the red cells and the RDW is a relative measure of the variation in size of the red cell population. A low hematocrit with a low MCV with a high RDW suggests a chronic iron-deficient erythropoiesis, but a normal RDW suggests a blood loss that is more acute, such as a hemorrhage.

Groups of individuals at risk for developing anemia include:

• infants without adequate iron intake
• children going through a rapid growth spurt, during which the iron available cannot keep up with the demands for a growing red cell mass
• women in childbearing years with an excessive need for iron because of blood loss during menstruation
• pregnant women, in whom the growing fetus creates a high demand for iron
• patients with chronic kidney disease, as their kidneys no longer secrete sufficient levels of the hormone erythropoietin, which stimulates red blood cell production by the bone marrow.

Urine is a sterile, liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream. These by-products are eventually expelled from the body in a process known as micturition, the primary method for excreting water-soluble chemicals from the body. These chemicals can be detected and analyzed by urinalysis. Amniotic fluid is closely related to urine, and can be analyzed by amniocentesis.

Physiology

To eliminate soluble wastes, which are toxic, most animals have excretory systems. In humans soluble wastes are excreted by way of the urinary system, which consists of the kidneys, ureters, urinary bladder, and urethra. The kidneys extract the soluble wastes from the bloodstream, as well as excess water, sugars, and a variety of other compounds. Remaining fluid contains high concentrations of urea and other substances, including toxins. Urine flows through these structures: the kidney, ureter, bladder, and finally the urethra. Urine is produced by a process of filtration, reabsorption, and tubular section.

Composition

Exhaustive detailed description of the composition of human urine can be found in NASA Contractor Report No. NASA CR-1802, D. F. Putnam, July 1971. That report provided detailed chemical analyses for inorganic and organic constituents, methods of analysis, chemical and physical properties and its behavior during concentrative processes such as evaporation, distillation and other phisiochemical operations. Urine is an aqueous solution of greater than 95% water, with the remaining constituents, in order of decreasing concentration urea 9.3 g/l, chloride 1.87 g/l, sodium 1.17 g/l, potassium 0.750 g/l, creatinine 0.670 g/l and other dissolved ions, inorganic and organic compounds.

Urine is sterile until it reaches the urethra where the epithelial cells lining the urethra are colonized by facultatively aerobic Gram negative rods and cocci.^[1] Subsequent to elimination from the body, urine can acquire strong odors due to bacterial action^{[citation needed]}. Most noticeably, the asphyxiating ammonia is produced by breakdown of urea. Some diseases alter the quantity and consistency of the urine, such as sugar as a consequence of diabetes.

Hazards

Urine is not toxic^{[citation needed]} though it can be irritating to skin and eyes and requires extra water for the body to process. High concentrations in the blood can cause damage to organs of the body. However, after suitable processing (as is done, for example, on the International Space Station), it is possible to extract potable water for drinking.

Characteristics

The typical color can range from clear to a dark amber, depending mostly upon the level of hydration of the body, among other factors.

Chemical analysis

Urea structure

Urine contains a range of substances that vary with what is introduced into the body. Aside from water, urine contains an assortment of inorganic salts and organic compounds, including proteins, hormones, and a wide range of metabolites.

Unusual color

Urine is a transparent solution that can range from colorless to amber but is usually a pale yellow. Colorless urine indicates over-hydration, which is usually considered much healthier than dehydration. In the context of a drug test, it could indicate a potential attempt to avoid detection of illicit drugs in the bloodstream through over-hydration.^[2]

• Dark yellow urine is often indicative of dehydration.
• Yellowing/light orange may be caused by removal of excess B vitamins from the bloodstream.
• Certain medications such as rifampin and pyridium can cause orange urine.
• Bloody urine is termed hematuria, potentially a sign of a bladder infection.
• Dark orange to brown urine can be a symptom of jaundice, rhabdomyolysis, or Gilbert's syndrome.
• Black or dark-colored urine is referred to as melanuria and may be caused by a melanoma.
• Fluorescent yellow / greenish urine may be caused by dietary supplemental vitamins, especially the B vitamins.
• Consumption of beets can cause urine to have a pinkish tint, and asparagus consumption can turn urine greenish.
• Reddish or brown urine may be caused by porphyria. Although again, the consumption of beets can cause the urine to have a harmless, temporary pink or reddish tint.

Odor

The smell of urine can be affected by the consumption of food. Eating asparagus is known to cause a strong odor in human urine. This is due to the body's breakdown of asparagusic acid.^[3] Other foods (and beverages) that contribute to odor include curry, alcohol, coffee, turkey, and onion.^[4][5]

Turbidity

Turbid urine may be a symptom of a bacterial infection, but can also be due to crystallization of salts such as calcium phosphate.^{[citation needed]}

pH

The pH of urine is close to neutral (7) but can normally vary between 4.4 and 8. In persons with hyperuricosuria, acidic urine can contribute to the formation of stones of uric acid in the kidneys, ureters, or bladder.^[6] Urine pH can be monitored by a physician^[7] or at home.

A diet high in citrus, vegetables, or dairy can increase urine pH (more basic). Some drugs also can increase urine pH, including acetazolamide, potassium citrate, and sodium bicarbonate.

A diet high in meat or cranberries can decrease urine pH (more acidic). Drugs that can decrease urine pH include ammonium chloride, chlorothiazide diuretics, and methenamine mandelate.^[8][9]

Volume

The amount of urine produced depends on numerous factors including state of hydration, activities, environmental factors, size, and health. In adult humans the average production is about 1 - 2 L per day. Producing too much or too little urine needs medical attention: Polyuria is a condition of excessive production of urine (> 2.5 L/day), in contrast to oliguria where < 400 mL are produced per day, or anuria with a production of < 100 mL per day.

Density or specific gravity

Normal urine density or specific gravity values vary between 1.003–1.035 (g·cm⁻³) , and any deviations may be associated with urinary disorders.

Urine in medicine

A Doctor Examining Urine. Trophime Bigot.

Examination

Many physicians in history have resorted to the inspection and examination of the urine of their patients. Hermogenes wrote about the color and other attributes of urine as indicators of certain diseases. Abdul Malik Ibn Habib of Andalusia d.862CE, mentions numerous reports of urine examination throughout the Umayyad empire.^[10] Diabetes mellitus got its name because the urine is plentiful and sweet. A urinalysis is a medical examination of the urine and part of routine examinations. A culture of the urine is performed when a urinary tract infection is suspected. A microscopic examination of the urine may be helpful to identify organic or inorganic substrates and help in the diagnosis.

The color and volume of urine can be reliable indicators of hydration level. Clear and copious urine is generally a sign of adequate hydration, dark urine is a sign of dehydration. The exception occurs when alcohol, caffeine, or other diuretics are consumed, in which case urine can be clear and copious and the person still be dehydrated.

Application

Aztec physicians used urine to clean external wounds to prevent infection, and administered it as a drink to relieve stomach and intestinal problems.^{[citation needed]}. In India, the ancient 'ayurvedic' medicinal system calls urine 'shivambu' and there is lot of information on 'shivambu therapy' on the web. Chinese folk medicine also documents use of boys' urine as a remedy when herbal medicines are not available.^{[citation needed]}

Resource

Urine contains proteins and other substances that are useful for medical therapy and are ingredients in many prescription drugs (e.g., Ureacin, Urecholine, Urowave)^{[citation needed]}. Urine from postmenopausal women is rich in gonadotropins that can yield follicle stimulating hormone and luteinizing hormone for fertility therapy^{[citation needed]}. The first such commercial product was Pergonal^{[citation needed]}. Urine from pregnant women contains enough human chorionic gonadotropins for commercial extraction and purification to produce hCG medication. Pregnant mare urine is the source of estrogens, namely Premarin^{[citation needed]}. Urine also contains antibodies, which can be used in diagnostic antibody tests for a range of pathogens, including HIV-1.^[11]

Other uses

Munitions

Urine has been used in the manufacture of gunpowder. Urine, a nitrogen source, was used to moisten straw or other organic material, which was kept moist and allowed to rot for several months to over a year. The resulting salts were washed from the heap with water, which was evaporated to allow collection of crude saltpeter crystals, that were usually refined before being used in making gunpowder.^[12]

Textiles

Urine has often been used as a mordant to help prepare textiles, especially wool, for dyeing. In Scotland, the process of "walking" (stretching) the tweed is preceded by soaking in urine.^[13]

Agriculture

Urine contains large quantities of nitrogen (mostly as urea), as well as significant quantities of dissolved phosphates and potassium, the main macronutrients required by plants. Diluted at least 8:1 with water it can be applied directly to soil as a fertilizer. Undiluted, it can chemically burn the roots of some plants, but it can be safely used as a source of complementary nitrogen in carbon rich compost.^[14] Urine typically contains 70% of the nitrogen and more than half the phosphorus and potassium found in urban waste water flows, while making up less than 1% of the overall volume. Thus source separation and on-site treatment has been studied in Sweden as a way to partially close the cycle of agricultural nutrient flows, to reduce the cost and energy intensivity of sewage treatment, and the ecological consequences such as eutrophication, resulting from an influx of nutrient rich effluent into aquatic or marine ecosystems. The fertilization effect of urine has been found to be comparable to that of commercial fertilizers with an equivalent NPK rating. ^[15]

However, depending on the diet of the producer, urine may also have undesirably high concentrations of various inorganic salts such as sodium chloride, which are also excreted by the renal system. Concentrations of heavy metals such as lead, mercury, and cadmium, commonly found in solid human waste, are much lower in urine (though not low enough to qualify for use in organic agriculture under current EU rules).^[16] Proponents of urine as an agricultural fertilizer usually claim the risks to be negligible or acceptable, and point out that sewage causes more environmental problems when it is treated and disposed of compared with when it is used as a resource.

It is unclear whether source separation and on site treatment of urine can be made cost effective, and to what degree the required behavioral changes would be regarded as socially acceptable, as the largely successful trials performed in Sweden may not readily generalize to other industrialized societies.^[15] In developing countries, the application of pure urine to crops is rare, but the use of whole raw sewage (termed night soil) has been common throughout history.

Survival uses

Numerous survival instructors and guides,^{[17][18][19][20][21][22]} including the US Army Field Manual,^[23] advise against drinking urine for survival. These guides explain that drinking urine tends to worsen, rather than relieve dehydration due to the salts in it, and that urine should not be consumed in a survival situation, even when there is no other fluid available.

During World War I, the Germans experimented with numerous poisonous gases for use during war. After the first German chlorine gas attacks, Allied troops were supplied with masks of cotton pads that had been soaked in urine. It was believed that the ammonia in the pad neutralized the chlorine. These pads were held over the face until the soldiers could escape from the poisonous fumes, although it is now known that chlorine gas reacts with urine to produce toxic fumes (see chlorine and Use of poison gas in World War I).^{[citation needed]}

Urban myth states that urine works well against jellyfish stings, and this scenario was demonstrated on a Season 4 episode of the NBC-TV show Friends "The One With the Jellyfish", an early episode of the CBS-TV show Survivor and the documentary film The Real Cancun. At best, it is ineffective and in some cases this treatment may make the injury worse

A spasm is a sudden, involuntary contraction of a muscle, a group of muscles,^[1] or a hollow organ, or a similarly sudden contraction of an orifice. It is sometimes accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes. Spasmodic muscle contraction may also be due to a large number of medical conditions, including the dystonias.

By extension, a spasm is a temporary burst of energy, activity, emotion, stress, or anxiety.

A subtype of spasms is colic, an episodic pain due to spasms of smooth muscle in a particular organ (e.g. the bile duct). A characteristic of colic is the sensation of having to move about, and the pain may induce nauseavomiting if severe. Series of spasms or permanent spasms are called a spasmism. or

In very severe cases, the spasm can induce muscular contractions that are more forceful than the sufferer could generate under normal circumstances. This can lead to torn tendons and ligaments.

Hysterical strength is argued to be a type of spasm induced by the brain under extreme circumstances.

Spasms can be caused by insufficient hydration, muscle overload or absence of some minerals (such as magnesium).

In human anatomy, the groin areas are the two creasestorso with the legs, ^[1] on either side of the pubic area.^[2] A pulled groin muscle usually refers to a painful injury sustained by straining the hip adduction muscles.^[3] at the junction of the

The term is sometimes used as a euphemism for sex organs since the names of the sex organs are taboo words in some cultures.

For vascular surgeons the groin is the preferred site for incisions to enter a catheter into the vascular system.

Urolithiasis (from Greek oûron, "urine" and lithos, "stone") is the condition where urinary calculi are formed^[1] in the urinary tract.^[2][3]

The term kidney stone (or "renal calculus") is sometimes used to refer to urolithiasis in any part of the urinary tract, however it is more properly reserved for stones that are actually in the collecting duct of the kidney itself.^[4][5][6]

The term nephrolithiasis can be used to describe the condition of having kidney stones,^[7] and ureterolithiasis can be used to describe the condition of having stones in the ureter.^[8]

Obstruction of the ureter by the kidney stones causes a renal colic attack which is why intense pain is felt in groin and back.

The term bladder stone is more frequently associated with veterinary science.

Pathology

Bladder stones are small particles that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is dehydrated. This allows for the minerals like calcium or magnesium to crystallize and form stones. Bladder stones vary in number size and consistency. In some cases bladder stones do not cause any symptoms of signs and are discovered as an incidental finding on a plain x ray. However, when symptoms do occur these may include severe lower abdominal and back pain, difficulty urination, frequent urination at night, fever, painful urination and blood in the urine. The majority of individuals who are symptomatic will complain of pain which comes in waves. The pain may also be associated with nausea, vomiting and chills.^[10]

Bladder stones vary in their size, shape and texture- some are small, hard and smooth whereas others are huge, spiked and very soft. One can have one or multiple stones. Bladder stones are somewhat more common in men who have prostate enlargement. The large prostate presses on the urethra and makes it difficult to pass urine. Over time stagnant urine collects in the bladder and minerals like calcium start to precipitate. Other individuals who develop bladder stones include those who have had spinal cord injury, paralysis or some type of nerve damage. When nerves to the back are damaged, the bladder cannot empty and stagnant urine results.^[11]

Causes

Bladder stones can also occur if the bladder gets inflamed or one has frequent insertion of urinary catheters. Some people who are paralyzed and unable to pass urine require small plastic tubes (catheters) placed in the bladder. These tubes are prone to infection which irritates the bladder resulting in stone formation. Finally kidney stones can travel down the ureter into the bladder and grow in to bladder stones. There is some evidence indicating that chronic irritation of the bladder by retained stones may increase the chance of bladder cancer.

Diagnosis

The diagnosis of bladder stone includes urine analysis, ultrasound, x rays or cystoscopy (inserting a small thin camera into the urethra and viewing the bladder). In the past a study called the intravenous pyelogram was frequently used to assess the presence of kidney stones. This test involves injecting a dye which is passed slowly into the urinary system. X ray images are then obtained every few minutes to determine if there is any obstruction to the dye as it is excreted into the bladder. Today, Intravenous Pyelogram has been replaced at most rural health centers by Ct scans. CT scans are more sensitive and can identify very small stones not seen by another other test.^[12]

Treatment

The treatment of bladder stones is simple. One needs to start drinking a lot of fluids. While any fluids can be consumed, water is considered to be the ideal solution. Excess fluid can help pass the small stones. Large stones or those that fail to pass may require other methods of treatment.^[13]

Breaking up of bladder stones is also done with a camera (cystoscope) which is inserted into the bladder. The surgeon visualizes the stone and use ultrasound or another mechanical device to break the stones into small pieces which are then flushed out. The procedure does require some type of anesthesia and may require admission to a hospital for several days. Complications of this treatment include infections, small tear of the bladder or bleeding in the urine.^[14]

Surgery

Sometimes stones are just too large and may need open surgery. In such a case, the bladder is opened and the stones are removed. Surgery is usually the last step and is considered a major procedure.

Prevention

The best way to prevent bladder stones is to prevent them in the first place. This means drinking plenty of liquids. If you sweat a lot, exercise intensely or live in a hot environment, drink 6-10 glasses of water on a daily basis. One should avoid drinking excess tea as there is evidence that this beverage can stimulate formation of bladder stones. If one does develop bladder irritation or urgency to urinate, drink cranberry juice because it has been shown to prevent development of small stones. Finally men who have difficulty with urination and are found to have prostatic hypertrophy should seek treatment

In anatomy, the urinary bladder is the organ that collects urine excreted by the kidneys prior to disposal by urination. A hollow^[1] muscular, and distensible (or elastic) organ, the bladder sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra.

Embryologically, the bladder is derived from the urogenital sinus and, it is initially continuous with the allantois. In males, the base of the bladder lies between the rectum and the pubic symphysis. It is superior to the prostate, and separated from the rectum by the rectovesical excavation. In females, the bladder sits inferior to the uterus and anterior to the vagina. It is separated from the uterus by the vesicouterine excavation. In infants and young children, the urinary bladder is in the abdomen even when empty.

Detrusor muscle

The detrusor muscle is a layer of the urinary bladder wall made of smooth muscle fibers arranged in spiral, longitudinal, and circular bundles. When the bladder is stretched, this signals the parasympathetic nervous system to contract the detrusor muscle. This encourages the bladder to expel urine through the urethra.

For the urine to exit the bladder, both the autonomically controlled internal sphincter and the voluntarily controlled external sphincter must be opened. Problems with these muscles can lead to incontinence. If the amount of urine reaches 100% of the urinary bladder's capacity, the voluntary sphincter becomes involuntary and the urine will be ejected instantly.

The urinary bladder usually holds 300-350 mL of urine; a full adult bladder holds about 500mL of urine, 15 times its empty volume. Not all specialists accept these values, some say a urinary bladder can hold ca. 1000 mL, but it is different from person to person. As urine accumulates, the rugae flatten and the wall of the bladder thins as it stretches, allowing the bladder to store larger amounts of urine without a significant rise in internal pressure.^[3]

The desire to urinate usually starts when the bladder reaches around 125% of its working volume. At this stage it is easy for the subject, if desired, to resist the urge to urinate. As the bladder continues to fill, the desire to urinate becomes stronger and harder to ignore. Eventually, the bladder will fill to the point where the urge to urinate becomes overwhelming, and the subject will no longer be able to ignore it.

Since the urinary bladder has a transitional epithelium, it does not produce mucus

Fundus

The fundus of the urinary bladder is the base of the bladder, formed by the posterior wall. It is lymphatically drained by the external iliac lymph nodes. The peritoneum lies superior to the fundus.

Disorders

Disorders of or related to the bladder include:

• Bladder cancer
• Bladder exstrophy
• Bladder infection
• Bladder spasm
• Bladder sphincter dyssynergia, a condition in which the sufferer cannot coordinate relaxation of the urethra sphincter with the contraction of the bladder muscles
• Bladder stones
• Cystitis
• Hematuria, or presence of blood in the urine, is a reason to seek medical attention without delay, as it is a symptom of bladder cancer as well as bladder and kidney stones.
• Interstitial Cystitis
• Overactive bladder, a condition which affects a large number of people.
• Urinary incontinence
• Urinary retention

In other animals

The bladder of fishes is generally small, and is not homologous with that of tetrapods. In lobe-finned fish, primitive ray-finned fish, and in many female cartilaginous fish, the bladder is formed from the fused ends of the archinephric ducts, counterparts of the mammalian ureters. In male sharks and rays, however, these ducts are only used for passage of sperm, and do not form a bladder. However, a bladder is sometimes found in these fish, developed from additional urinary ducts posterior to the archinephric ducts.^[5]

In teleosts and lampreys, the bladder forms from part of the wall of the cloaca, where it is present at all, although the archinephric ducts are usually also involved in its formation. Like that of other fish, it is not lined by the transitional epithelium found in tetrapods.^[5]

The bladder of amphibians and reptiles is a pocket in the cloaca, and is usually not connected with the urinary ducts at all. Only in mammals, most of which have no cloaca, does the bladder take on the general form seen in humans. Many reptiles, including snakes and crocodilians, have no bladder, and the only bird species to have a bladder is the ostrich.^[5]

Uses

Besides its normal use to the possessor, animal bladders (usually pig bladders) have been used to make balls (such as footballs) and even a musical instrument, the bumbass.

Kidney stones (ureterolithiasis) result from stones or renal calculi (from Latin ren, renes, "kidney" and calculi, "pebbles"^[1]) in the ureter. The stones are solid concretions or calculi (crystal aggregations) formed in the kidneys from dissolved urinary minerals. Nephrolithiasis (from Greek νεφρός (nephros, "kidney") and λιθoς (lithos, "stone")) refers to the condition of having kidney stones. Urolithiasis refers to the condition of having calculi in the urinary tract (which also includes the kidneys), which may form or pass into the urinary bladder. Ureterolithiasis is the condition of having a calculus in the ureter, the tube connecting the kidneys and the bladder. The term bladder stones usually applies to urolithiasis of the bladder in non-human animals such as dogs and cats.

Kidney stones typically leave the body by passage in the urine stream, and many stones are formed and passed without causing symptoms. If stones grow to sufficient size before passage on the order of at least 2-3 millimeters they can cause obstruction of the ureter. The resulting obstruction causes dilation or stretching of the upper ureter and renal pelvis (the part of the kidney where the urine collects before entering the ureter) as well as muscle spasm of the ureter, trying to move the stone. This leads to pain, most commonly felt in the flank, lower abdomen and groin (a condition called renal colic). Renal colic can be associated with nausea and vomiting. There can be blood in the urine, visible with the naked eye or under the microscope (macroscopic or microscopic hematuria) due to damage to the lining of the urinary tract.

There are several types of kidney stones based on the type of crystals of which they consist. The majority are calcium oxalate stones, followed by calcium phosphate stones. More rarely, struvite stones are produced by urea-splitting bacteria in people with urinary tract infections, and people with certain metabolic abnormalities may produce uric acid stones or cystine stones.

The diagnosis of a kidney stone can be confirmed by radiological studies and or ultrasound examination; urine tests and blood tests are also commonly performed. When a stone causes no symptoms, watchful waiting is a valid option. In other cases, pain control is the first measure, using for example non-steroidal anti-inflammatory drugs or opioids. Using soundwaves, some stones can be shattered into smaller fragments (this is called extracorporeal shock wave lithotripsy). Sometimes a procedure is required, which can be through a tube into the urethra, bladder and ureter (ureteroscopy), or a keyhole or open surgical approach from the kidney's side. Sometimes, a tube may be left in the ureter (a ureteric stent) to prevent the recurrence of pain. Preventive and structive measures are often advised such as drinking sufficient amounts of water and milk although the effect of many dietary interventions has not been rigorously studied.

Causes

Kidney stones or calcium oxalate crystals in kidney can be due to underlying metabolic conditions, such as renal tubular acidosis,^[7] Dent's disease,^[8] hyperparathyroidism,^[9] primary hyperoxaluria^[10] and medullary sponge kidney.^[11] Kidney stones are also more common in patients with Crohn's disease.^[12] Patients with recurrent kidney stones should be screened for these disorders. This is typically done with a 24 hour urine collection that is chemically analyzed for deficiencies and excesses that promote stone formation.^[13]

There has been some evidence that water fluoridation may increase the risk of kidney stone formation. In one study, patients with symptoms of skeletal fluorosis were 4.6 times as likely to develop kidney stones.^[14]

A 1998 paper in the Archives of Internal Medicine examined the sources of a widely-held belief in the medical community that vitamin C can cause kidney stones, and found it to be based on several circular references, ultimately attributing the belief to a wider pattern of skepticism regarding efficacy of vitamin supplements.^[15] A more recent study suggested a causal relationship may exist, but it was not conclusive.^[16]

The American Urological Association has projected that increasing global temperatures will lead to greater future prevalence of kidney stones, notably by expanding the "kidney stone belt" of the southern United States.^[17] Astronauts seem to show a higher risk of developing kidney stones during or after long duration space flights.^[18]

Calcium oxalate stones

The most common type of kidney stone is composed of calcium oxalate crystals, occurring in about 80% of cases,^[7] and the factors that promote the precipitation of crystals in the urine are associated with the development of these stones.

Common sense has long held that consumption of too much calcium could promote the development of calcium kidney stones. However, current evidence suggests that the consumption of low-calcium diets is actually associated with a higher overall risk for the development of kidney stones.^[2] This is perhaps related to the role of calcium in binding ingested oxalate in the gastrointestinal tract. As the amount of calcium intake decreases, the amount of oxalate available for absorption into the bloodstream increases; this oxalate is then excreted in greater amounts into the urine by the kidneys. In the urine, oxalate is a very strong promoter of calcium oxalate precipitation, about 15 times stronger than calcium.

Uric acid (urate)

About 5–10% of all stones are formed from uric acid.^[7] Uric acid stones form in association with conditions that cause hyperuricosuria with or without high blood serum uric acid levels (hyperuricemia); and with acid/base metabolism disorders where the urine is excessively acidic (low pH) resulting in uric acid precipitation. A diagnosis of uric acid nephrolithiasis is supported if there is a radiolucent stone, a persistent undue urine acidity, and uric acid crystals in fresh urine samples.^[19]

Other types

Other types of kidney stones are composed of struvite (magnesium, ammonium and phosphate); calcium phosphate; and cystine.

Struvite stones are also known as infection stones, urease or triple-phosphate stones. About 10–15% of urinary calculi consist of struvite stones.^[20] The formation of struvite stones is associated with the presence of urea-splitting bacteria,^[21] most commonly Proteus mirabilis (but also Klebsiella, Serratia, Providencia species). These organisms are capable of splitting urea into ammonia, decreasing the acidity of the urine and resulting in favorable conditions for the formation of struvite stones. Struvite stones are always associated with urinary tract infections.^[20]

The formation of calcium phosphate stones is associated with conditions such as hyperparathyroidism and renal tubular acidosis.

Formation of cystine stones is uniquely associated with people suffering from cystinuria, who accumulate cystine in their urine. Cystinuria can be caused by Fanconi's syndrome.