Respiratory alkalosis 

is a medical condition in which increased respiration elevates the

blood pH beyond the normal range (7.35–7.45) with a concurrent reduction in arterial levels
of carbon dioxide.[1][4] This condition is one of the four primary disturbance of acid–base
homeostasisTetany or tetanic seizure is a medical sign consisting of the involuntary contraction
of muscles, which may be caused by disorders that increase the action potential frequency of
muscle cells or the nerves that innervate them.
Muscle cramps caused by the disease tetanus are not classified as tetany; rather, they are due to a
lack of inhibition to the neurons that supply muscles. Tetanic contractions (physiologic tetanus) are a
broad range of muscle contraction types, of which tetany is only one.
Tetany is characterized by contraction of distal muscles of the hands (carpal spasm with extension
of interphalangeal joints and adduction and flexion of the metacarpophalangeal joints) and feet
(pedal spasm) and is associated with tingling around the mouth and distally in the limbs.[citation needed]

Causes[edit]

Cow grazing on rapidly grown pasture with tetany of the neck suggesting grass tetany[1]

 The usual cause of tetany is a deficiency of calcium. An excess of phosphate (high phosphate-

to-calcium ratio) can also trigger the spasms.[2][3]
 Underfunction of the parathyroid gland can lead to tetany.
 Low levels of carbon dioxide cause tetany by altering the albumin binding of calcium such that
the ionized (physiologically influencing) fraction of calcium is reduced; one common reason for
low carbon dioxide levels is hyperventilation.[4]
 Low levels of magnesium can lead to tetany.[5][6]
 Clostridium tetani toxin, via inhibition of glycine-mediated and GABA-ergic neurotransmission,
may lead to tetany.[verification needed]

 An excess of potassium in grass hay or pasture can trigger winter tetany, or grass tetany,

in ruminants.[verification needed]
 Osteomalacia and rickets due to deficiency of vitamin D[verification needed]
Metabolic alkalosis with hypokalemia like Gitelman syndrome and Bartter's syndrome can cause
tetany. Vomiting induced alkalosis and hyperventilation induced respiratory alkalosis also cause
tetany because of neuronal irritability.[citation needed]

Pathophysiology[edit]
Hypocalcemia is the primary cause of tetany. Low ionized calcium levels in the extracellular
fluid increase the permeability of neuronal membranes to sodium ion, causing a progressive
depolarization, which increases the possibility of action potentials. This occurs because calcium ions
interact with the exterior surface of sodium channels in the plasma membrane of nerve cells and
hypocalcemia effectively increases resting potential (rendering the cells more excitable) since less
positive charge is present extracellularly. When calcium ions are absent the voltage level required to
open voltage gated sodium channels is significantly altered (less excitation is required).[7] If the
plasma Ca2+ decreases to less than 50% of the normal value of 9.4 mg/dl, action potentials may be
spontaneously generated, causing contraction of peripheral skeletal muscles. Hypocalcemia is not a
term for tetany but is rather a cause of tetany.

Diagnosis[edit]
French Professor Armand Trousseau (1801–1867) devised the maneuver of occluding the brachial
artery by squeezing, to trigger cramps in the fingers. This is now known as the Trousseau sign of
latent tetany.[8]
Also, tetany can be demonstrated by tapping anterior to the ear, at the emergence of the facial
nerve. A resultant twitch of the nose or lips suggests low calcium levels. This is now known as
the Chvostek sign.[citation needed]
EMG studies reveal single or often grouped motor unit discharges at low discharge frequency during
tetany episodes.[citation needed]
Clostridium tetani is a common soil bacterium and the causative agent of tetanus. Vegetative cells
of C. tetani are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis
racket- or drumstick-shaped when forming spores. C. tetani spores are extremely hardy and can be
found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, C.
tetani can grow and produce a potent toxin, tetanospasmin, which interferes with motor neurons,
causing tetanus. The toxin's action can be prevented with tetanus toxoid vaccines, which are often
administered to children worldwideClostridium tetani is a rod-shaped, Gram-positive bacterium,
typically up to 0.5 μm wide and 2.5 μm long.[1] It is motile by way of various flagella that surround its
body.[1] C. tetani cannot grow in the presence of oxygen.[1] It grows best at temperatures ranging from
33 to 37°C.[1]
Upon exposure to various conditions, C. tetani can shed its flagella and form a spore.[1] Each cell can
form a single spore, generally at one end of the cell, giving the cell a distinctive drumstick shape.[1] C.
tetani spores are extremely hardy and are resistant to heat, various antiseptics, and boiling for
several minutes.[2] The spores are long-lived and are distributed worldwide in soils as well as in the
intestines of various livestock and companion animals.[3]

Evolution[edit]
Clostridium tetani is classified within the genus Clostridium, a broad group of over 150 species of
Gram-positive bacteria.[3] C. tetani falls within a cluster of nearly 100 species that are more closely
related to each other than they are to any other genus.[3] This cluster includes other
pathogenic Clostridium species such as C. botulinum and C. perfringens.[3] The closest relative to C.
tetani is C. cochlearium.[3] Other Clostridium species can be divided into a number of genetically
related groups, many of which are more closely related to members of other genera than they are
to C. tetani.[3] Examples of this include the human pathogen C. difficile, which is more closely related
to members of genus Peptostreptococcus than to C. tetani.[4]

Role in the disease[edit]

A man suffering muscle spasms from tetanus, painted by Charles Bell in 1809

While C. tetani is frequently benign in the soil or in the intestinal tracts of animals, it can sometimes
cause the severe disease tetanus. Disease generally begins with spores entering the body through a
wound.[5] In deep wounds, such as those from a puncture or contaminated needle injection the
combination of tissue death and limited exposure to surface air can result in a very low-oxygen
environment, allowing C. tetani spores to germinate and grow.[2] As C. tetani grows at the wound site,
it releases the toxins tetanolysin and tetanospasmin as cells lyse.[1] The function of tetanolysin is
unclear, although it may help C. tetani to establish infection within a wound.[6][1] Tetanospasmin
("tetanus toxin") is one of the most potent toxins known, with an estimated lethal dose less than
2.5 nanograms per kilogram of body weight, and is responsible for the symptoms of tetanus.[6]
[1]
 Tetanospasmin spreads via the lymphatic system and bloodstream throughout the body, where it
is taken up into various parts of the nervous system.[6] In the nervous system, tetanospasmin acts by
blocking the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric
acid at motor nerve endings.[5] This blockade leads to the widespread activation of motor
neurons and spasming of muscles throughout the body.[6] These muscle spasms generally begin at
the top of the body and move down, beginning about 8 days after infection with lockjaw, followed by
spasms of the abdominal muscles and the limbs.[5][6] Muscle spasms continue for several weeks.[6]
The gene encoding tetanospasmin is found on a plasmid carried by many strains of C. tetani; strains
of bacteria lacking the plasmid are unable to produce toxin.[1][5] The function of tetanospasmin in
bacterial physiology is unknown.[1]

Treatment and preventions[edit]

Clostridium tetani is susceptible to a number of antibiotics,
including chloramphenicol, clindamycin, erythromycin, penicillin G, and tetracycline.[3] However, the
usefulness of treating C. tetani infections with antibiotics remains unclear.[1] Instead, tetanus is often
treated with tetanus immune globulin to bind up circulating tetanospasmin.
[6]
 Additionally, benzodiazepines or muscle relaxants may be given to reduce the effects of the
muscle spasms.[1]
Damage from C. tetani infection is generally prevented by administration of a tetanus
vaccine consisting of tetanospasmin inactivated by formaldehyde, called tetanus toxoid.[1] This is
made commercially by growing large quantities of C. tetani in fermenters, then purifying the toxin
and inactivating in 40% formaldehyde for 4-6 weeks.[1] The toxoid is generally coadministered
with diphtheria toxoid and some form of pertussis vaccine as DPT vaccine or DTaP.[6] This is given in
several doses spaced out over months or years to elicit an immune response that protects the host
from the effects of the toxin.[6]

Researches[edit]
Clostridium tetani can be grown on various anaerobic growth media such as thioglycolate
media, casein hydrolysate media, and blood agar.[1] Cultures grow particularly well on media at a
neutral to alkaline pH, supplemented with reducing agents.[1] The genome of a C. tetani strain has
been sequenced, containing 2.80 million base pairs with 2,373 protein coding genes.[7]
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated
from chromosomal DNA and can replicate independently. They are most commonly found as small
circular, double-stranded DNA molecules in bacteria; however, plasmids are sometimes present
in archaea and eukaryotic organisms.[1][2] In nature, plasmids often carry genes that benefit the
survival of the organism and confer selective advantage such as antibiotic resistance. While
chromosomes are large and contain all the essential genetic information for living under normal
conditions, plasmids are usually very small and contain only additional genes that may be useful in
certain situations or conditions. Artificial plasmids are widely used as vectors in molecular cloning,
serving to drive the replication of recombinant DNA sequences within host organisms. In the
laboratory, plasmids may be introduced into a cell via transformation. Synthetic plasmids are
available for procurement over the internet.[3][4][5]
Plasmids are considered replicons, units of DNA capable of replicating autonomously within a
suitable host. However, plasmids, like viruses, are not generally classified as life.[6] Plasmids are
transmitted from one bacterium to another (even of another species) mostly through conjugation.
[7]
 This host-to-host transfer of genetic material is one mechanism of horizontal gene transfer, and
plasmids are considered part of the mobilome. Unlike viruses, which encase their genetic material in
a protective protein coat called a capsid, plasmids are "naked" DNA and do not encode genes
necessary to encase the genetic material for transfer to a new host; however, some classes of
plasmids encode the conjugative "sex" pilus necessary for their own transfer. The size of the plasmid
varies from 1 to over 200 kbp,[8] and the number of identical plasmids in a single cell can range
anywhere from one to thousands under some circumstances.
The term plasmid was introduced in 1952 by the American molecular biologist Joshua Lederberg to
refer to "any extrachromosomal hereditary determinant."[9] The term's early usage included any
bacterial genetic material that exists extrachromosomally for at least part of its replication cycle, but
because that description includes bacterial viruses, the notion of plasmid was refined over time to
comprise genetic elements that reproduce autonomously.[10] Later in 1968, it was decided that the
term plasmid should be adopted as the term for extrachromosomal genetic element,[11] and to
distinguish it from viruses, the definition was narrowed to genetic elements that exist exclusively or
predominantly outside of the chromosome and can replicate autonomously.[10]