document_title: McMuffin

question_text: when was the egg mcmuffin added to the menu

text: McMuffin

text: Product description[edit]

text: In the US and Canada the standard McMuffin consists of a slice of Canadian bacon,[2] a griddle-fried egg, and a slice of American cheese on a toasted and buttered English muffin. The round shape of the egg is made by cooking it in a white plastic ring surrounded by an outer metal structure.[3][1]

text: Variants[edit]

text:
McMuffin Sausage TS - sausage patty, lettuce, tomato, a special sauce and a slice of Cheddar cheese in an English muffin. Available in Germany[4]
Sausage McMuffin with Egg - A sausage patty is substituted for the Canadian bacon, and the cheese side of the muffin is switched. Introduced in 1984. Invention is credited to the innovation of McDonald's franchisees .[citation needed][5] In India, chicken is used for the sausage patty.
Sausage McMuffin - A value menu item without the egg.
Chicken McMuffin - A breaded chicken patty, lettuce, tomato, mayo and a slice of Cheddar cheese in an English muffin. There is no egg in this McMuffin variant. Available in Hungary and Germany as part of McDonald's regular breakfast menu.[6][4]
Bacon and Egg McMuffin - Pieces of streaky bacon are substituted for the Canadian bacon.[7]
Massive McMuffin - Ketchup, bacon, egg, American cheese and two sausage patties.
Available in New Zealand.[8]
Mega Muffin - Egg, double sausage, bacon, cheese, and ketchup. Available in South Africa[9] and periodically in Japan as a promotion.[citation needed]
Western Omelette McMuffin - Was available in 1990 and 1992; featured a Western omelette (Egg filled with ham, diced onions, and green bell peppers) and American cheese on a toasted English muffin.[10] This variant was sold in Canada from 1984 until 2007 as the "Omelette McMuffin".[citation needed]
Veg McMuffin - Available in India to cater to the substantial part of the population in India that doesn't consume egg.[11]
Egg McMuffin - 300 calories per serving with 12 grams of fat.[12]
McMuffin Chicken & Bacon: A breaded chicken patty, egg, bacon, ketchup, a special sauce and a slice of Cheddar cheese in an English muffin. Available in Germany.[4]
Egg White Delight - A variant substituting freshly scrambled egg whites for the normal round egg, and pasteurized process white Cheddar for the American cheese.[13]
Farmer's Muffin - A variant with sausage patty, cheddar cheese and horseradish/mustard sauce. Available in Poland. [14]
Mighty McMuffin - A variant with sausage patty, two rashers of bacon, cheese, ketchup and egg. Available in Australia. [15]

text: History[edit]

text: This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2010) (Learn how and when to remove this template message)

text: The McDonald's egg sandwich was invented in 1972.[16] Former McDonald's President Ray Kroc wrote that Herb Peterson and his assistant, Donald Greadel, the operator of a Santa Barbara, California franchise (located at 3940 State Street), asked Kroc to look at something, without giving details because it was:

text:
“
...a crazy idea — a breakfast sandwich. It consisted of an egg that had been formed in a Teflon circle with the yolk broken, and was dressed with a slice of cheese and a slice of grilled ham. It was served open-faced on a toasted and buttered English muffin. The advent of the Egg McMuffin opened up a whole new area of potential business for McDonald's, the breakfast trade.[3][1]
”

text: Peterson had first presented the Egg McMuffin at the Santa Barbara franchise without the knowledge of McDonald's Corporate, which at the time served only lunch and dinner at all their locations. When Corporate discovered the unauthorized breakfast offerings, it initially reprimanded him and threatened him with a number of penalties for breaking the franchise agreement.[citation needed]

text: The first McDonald's Corporate-authorized Egg McMuffin was served at the Belleville, New Jersey McDonald's in 1972.

text: In the 1970s, some McDonald's restaurants served Egg McMuffins all day as a promotion.

text: In several cities, such as Hong Kong, Sausage & Egg McMuffins are served around the clock, because of the prominent use of the egg in meals other than breakfast in those countries; the muffins and sausage patty there are softer than the usual variant to suit local customers. Until 2015, US restaurants usually restricted the item to the breakfast menu. This is mainly because the grill temperature required to cook beef patties is significantly different from the temperature at which eggs are cooked, according to Herb Peterson in a special episode of Unwrapped. Because of this, beef patties and Egg McMuffins cannot be cooked on the same grill, meaning that to keep Egg McMuffins available all day, a store would have to have a separate grill dedicated specifically to Egg McMuffins; this would either mean sacrificing a grill that could have been used for beef patties or buying an additional grill.

text: Cultural impact[edit]

text: An attendant at president Donald Trump's "Thank You" speech in Orlando lampooned Independent politician Evan McMullin's last name as "McMuffin", a reference to the McDonald's breakfast item of the same name.[17]

text: Advertising[edit]

text: This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2008) (Learn how and when to remove this template message)

text: The Massive McMuffin was introduced to coincide with the Australian Football League and Australian National Rugby League seasons of 1998, when McDonald's Australia launched the Footy Burger (now the Double Quarter Pounder), Mini Footy Burger (double Cheeseburger) and Massive McMuffin. The muffin proved so popular that some Australian stores kept the item as a permanent breakfast option.

text: In the Philippines, to celebrate the annual National Breakfast Day, they distribute free McMuffins for the first 100 customers in all branches nationwide from 6 am until supplies last, with optional McCafe coffee for an additional charge.


document_title: Sarah & Duck

question_text: who is the narrator of sarah and duck

question_tokens: who is the narrator of sarah and duck

root

text: Sarah & Duck

text: Premise[edit]

text: The series follows the adventures of Sarah, a very kind, polite seven-year-old girl, with big eyes, rosy cheeks and a green hat,[7] and her best friend Duck, a mallard. The central theme is the relationship between these two characters and the adventures they have together. CBeebies state that the show has two learning themes: 'Friendship and imagination' and 'Problem Solving'.[8]

tag: p

text: Cast and characters[edit]

text:
Name

Voice cast[9]

About

Sarah
Tasha Lawrence[10]
She is a very kind, polite and somewhat eccentric seven-year-old[10] girl. She is best friends with Duck. She plays the tuba, likes sea cows (manatees), and drinks "lemon water".

Duck
N/A
He is Sarah's quacky, flappy best friend. Duck wants to be a penguin and has a toy robot. He turns two years old in series 1.[11]

Narrator
Roger Allam[12]
He talks to Sarah & Duck, asks them questions and gives them suggestions.  There is a possibility that the Narrator is Sarah's father, given the reference made in 'Old Toys'.

Scarf Lady
Lesley Nicol[13]
She is a forgetful old lady who loves knitting. She lives in a house full of woollen items. She has a talking knitting bag and a pet donkey.

Bag
Andy Nyman
He is Scarf Lady's knitting bag. He corrects Scarf Lady when she gets confused.

Donkey
N/A
He is Scarf Lady's pet. He looks sad but isn't really.

tag: table

text: Other characters[edit]

text:
John is Sarah's Japanese friend voiced by Luca Pilkington Massey.
Flamingo is John's pet voiced by Tim O'Sullivan.
The Shallots are planted by Sarah & Duck in the first episode. There are three similar-sized and one tiny one. The three repeat the same phrase when spoken to while the tiny one says a variation thereof. They live in Sarah's front garden by the door, and are voiced by Tim O'Sullivan and Tony Clarke.
Rainbow makes friends with Sarah & Duck after a rain shower. He is very tickly, and voiced by David Carling.
Moon first meets Sarah & Duck at the Big Shop when he is heading to work at night. He is voiced by Pete Gallagher.
Venus is a good friend of Moon and normally Sarah only sees her at night.
Mars, a bruff Sergeant Major type character, joins Moon & Venus from time to time.
Hat Lady (or Hattie) is Scarf Lady's old sporting rival and runs the local hat museum. Like her arch-nemesis Scarf Lady, she is voiced by Lesley Nicol.
Umbrella is scared of the rain and voiced by Jamie Oram.
Bug is a large ladybird that lives in Sarah & Duck's house plant and collects buttons.
The Cloud Captain is a French engineer who operates the weather system from Sarah's local park, voiced by Derek Griffiths.
The Ribbon Sisters are Sarah & Duck's quiet next-door neighbours wearing differently-coloured large sunglasses. They like to play with ribbons and are voiced by Kiki Brooks.
Scooter Boy has a scooter and wears a helmet. He has been seen riding his scooter only once, and walks it everywhere he goes. He is voiced by Dylan Issberner.
Plate Girl carries a plate with her at most times and is voiced by Yaeli Miller.
Cake helps bake and is voiced by Andy Nyman.
Bread Man runs the local bakery, which Sarah and especially Duck like to visit.
Tortoise is slow and easily scared when he retreats into his shell which has windows he can look out. Tortoise doesn't speak.
Leftover Wool sits patiently in Scarf Lady's wool room, and is voiced by Andy Nyman.
Poetry Pete is first featured on one of Scarf Lady's LPs and is voiced by Simon Callow

tag: ul

text: Production[edit]

text: The series is produced using computer-assisted animation techniques and the Adobe After Effects[14] and CelAction2D[15] packages.

text: A second series began airing on 11 August 2014.

text: On 17 June 2015 it was renewed for a third series [16] which aired starting the 18 October 2016 on CBeebies.

text: Broadcast[edit]

text: BBC Worldwide have secured global distribution and merchandising rights for the new show and will air it to BBC Worldwide's network of channels.[17] On 19 August 2013, Sarah & Duck was first broadcast in the U.S., on Sprout. The first series of Sarah & Duck has also aired in Japan (NHK), Norway (NRK), Sweden (SVT), Denmark (DR), Finland (YLE), Germany (KiKa), Portugal (RTP), Iceland (RUV), the Netherlands (NPO) and Israel (HOP).[18] In Canada it is broadcast on the Family Jr. channel.[19] In Australia, it broadcasts on ABC Kids. On 12 February 2016 Sarah & Duck was made available in the U.S. on Netflix.[20]

text: Reception[edit]

text: A pilot for Sarah & Duck was first aired at the Cartoon Forum 2010[21] where it was warmly received. The series was an immediate hit in the UK, and the first four episodes were the most popular pre-school programmes of their week on the BBC catch-up TV service, iPlayer.[22]

text: The first episode 'Lots of Shallots' was part of the official selection for the 2013 Annecy International Animated Film Festival.[23]

text: In October 2013 Sarah & Duck was nominated for a Children's British Academy of Film and Television Arts (BAFTA) award in the pre-school animation category.[24] The BAFTA was awarded to Timmy Time.

text: In January 2014 Sarah & Duck was nominated in the pre-school category of the British Animation Awards.[25]

text: In November 2014, with a second nomination, Sarah & Duck won the British Academy of Film and Television Arts (BAFTA) award in the pre-school animation category.[26]

text: In February 2017, it was tied in the Kidscreen Award for best animated series with Doc McStuffins.[27]

text: Episodes[edit]

text:
Series

Episodes

Originally aired

First aired

Last aired

1

40

18 February 2013 (2013-02-18)

19 December 2013 (2013-12-19)

2

40

11 August 2014 (2014-08-11)

15 December 2015 (2015-12-15)

3

40

18 October 2016 (2016-10-18)

15 December 2017 (2017-12-15)

text: DVD Releases[edit]

text:
Release No.

Release Name

Episodes

Number and duration

R2 release date

1
Lots of Shallots and other stories
Lots of Shallots, Sarah Duck & the Penguin, Cheer Up Donkey, Cake Bake, Scarf Lady's House, Robot Juice, Bouncy Ball, Rainbow Lemon, Sit Shop, Kite Flight
70 mins
17 February 2014[28]

2
Doubles and other stories
Doubles, Umbrella and the Rain, Big Shop, Woollen Music, Fairground, Sarah Gets a Cold, Ribbon Sisters, Stargazing, Coloured Light, Strawberry Souffle
70 mins
8 September 2014[29]

3
Balloon Race and other stories
Balloon Race, Camera, Tapping Shoes, Fireworks Dance, Fancy Park, Pipe Conductor, Slow Quest, World Bread Day, Pond Princess, Puncture Pump[30]
70 mins
16 February 2015[31]

4
Petal Light Picking and other stories
Petal Light Picking, Bobsleigh, Plate Fog, Scared of Stairs, Moon Paint, The Play, Bread Bike, Bug's Button Bank, No More Wool, Octogon Club[32]
70 mins
19 October 2015[33]

5
Cloud Tower and other stories
Cloud Tower, Outside Outside, Umbrella Bubbles, Sound Jumble, The Mouse's Birthday, Tortoise Snooze, Fast Slow Bungalow, Bags of Bags, Ribbon Fall, Garden Gaming[34]
70 mins
15 February 2016[35]

6
Duck Hotel and other stories
Duck Hotel, Origami Overload, Shallot Circus, Toy Tidy, Plate Escape, The Big Sleepover, Paisley Sea, Duck's Quack, Rainbow's Niece, Decorating Donkey[36]
70 mins
16 May 2016[37]

7
Beach Break and other stories
Beach Break, Parasol Show, Extra Bounce, Cake Relocate, Lost Librarian, Scooter Stand Still, Music Fixer, Wool on Wheels, Lemon Cafe, Star Renovation[38]
70 mins
25 July 2016[39]

8
Duck Flies and other stories
Duck Flies, Seacow Snowtrail, Woolly Memories, Bubble Bumbling, Toggle Tangle, Tummy Talk, Moon's Exhibition, Pond Prose, The Art of Pink, Bug Bop[40]
70 mins
17 October 2016[41]

9
Train Fudge and other stories
Train Fudge, Picture Planes, Hat Fuss, Dewy Morning, Sticker Swap, Magic Panic, Birthday Buoy, Alarm Clock, Twang Ball, Auto Cat[42]
70 mins
20 February 2017[42]

10
Constable Quack and other stories
Constable Quack, Fluff Bread, Moonbow, Bench Blocked, Planetarium Aquarium, Shallot Boat, Cake Decorate, Balloon Barnacles, Basking Shark, Old Toys[43]
70 mins
2 October 2017[44]


document_title: South Asia

question_text: what is the second largest country in south asia

question_tokens: what is the second largest country in south asia

text: South Asia

text: Definitions[edit]

text: The total area of South Asia and its geographical extent is not clear cut as systemic and foreign policy orientations of its constituents are quite asymmetrical.[16] Aside from the central region of South Asia, formerly part of the British Empire, there is a high degree of variation as to which other countries are included in South Asia.[17][18][19][20]

text: Modern definitions of South Asia are consistent in including Afghanistan, India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan and Maldives as the constituent countries.[21][22][23][24][25][26] Myanmar is included by some scholars in South Asia, but in Southeast Asia by others.[18][27] Some do not include Afghanistan,[18] others question whether Afghanistan should be considered a part of South Asia or the Middle East.[28][29]

text: The current territories of Bangladesh, India, and Pakistan, which were the core of the British Empire prior to 1947, form the central region of South Asia, in addition to Afghanistan,[21][22][23][24][25][26] which was a British protectorate until 1919, after the Afghans lost to the British in the Second Anglo-Afghan war. The mountain countries of Nepal and Bhutan, and the island countries of Sri Lanka and Maldives are generally included as well. Myanmar (formerly Burma) is often added, and by various deviating definitions based on often substantially different reasons, the British Indian Ocean Territory and the Tibet Autonomous Region are included as well.[16][30][31][32][33][34][35][36][37]

text: The common concept of South Asia is largely inherited from the administrative boundaries of the British Raj,[38] with several exceptions. The Aden Colony, British Somaliland and Singapore, though administered at various times under the Raj, have not been proposed as any part of South Asia.[39] Additionally Burma was administered as part of the Raj until 1937, but is now considered a part of Southeast Asia and is a member state of ASEAN. The 562 princely states that were protected by but not directly ruled by the Raj became administrative parts of South Asia upon joining Union of India or Dominion of Pakistan.[40][41][42] Geopolitically, it had formed the whole territory of Greater India,[27][43]

text: The South Asian Association for Regional Cooperation (SAARC), a contiguous block of countries, started in 1985 with seven countries – Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan and Sri Lanka – and added Afghanistan as an eighth member in 2007.[44][45] China and Myanmar have also applied for the status of full members of SAARC.[46][47] This bloc of countries include two independent countries that were not part of the British Raj – Nepal, and Bhutan. Afghanistan was a British protectorate from 1878 until 1919, after the Afghans lost to the British in the Second Anglo-Afghan war. The World Factbook, based on geo-politics, people, and economy defines South Asia as comprising Afghanistan, Bangladesh, Bhutan, British Indian Ocean Territory, India, Maldives, Nepal, Pakistan, and Sri Lanka.[48] The South Asia Free Trade Agreement incorporated Afghanistan in 2011, and the World Bank grouping of countries in the region also includes all eight members comprising South Asia and SAARC as well,[49][50] and the same goes for the United Nations Children's Fund (UNICEF).[51][52]

text:
Definition by South Asian Studies programs

When the Centre for South Asian Studies at the University of Cambridge was established, in 1964, it promoted the study of India, Pakistan, Sri Lanka, Bangladesh, Afghanistan,[53][54][55][56] the Himalayan Kingdoms (Nepal, Bhutan, and Sikkim[57]), and Burma (now Myanmar). It has since included Thailand, Malaysia, Singapore, Vietnam, Cambodia, Laos, Indonesia, the Philippines and Hong Kong.[58]
The Centres for South Asian Studies at both the University of Michigan and the University of Virginia include Tibet along with the eight members of SAARC in their research programs, but exclude the Maldives.[59][60] The South Asian Studies Program of Rutgers University and the University of California, Berkeley Centre for South Asia Studies also include the Maldives.[61][62]
The South Asian Studies Program of Brandeis University defines the region as comprising "India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and in certain contexts Afghanistan, Burma, Maldives and Tibet".[63] The similar program of Columbia University includes Afghanistan, Bangladesh, India, the Maldives, Nepal, Pakistan, and Sri Lanka in their study and excludes Burma.[64]
See also: Indology

tag: div

text: The United Nations Statistics Division's scheme of sub-regions include all eight members of the SAARC as part of Southern Asia, along with Iran[65] only for statistical purposes.[66] Population Information Network (POPIN) includes Afghanistan, Bangladesh, Burma, India, Nepal, Pakistan and Sri Lanka as part of South Asia. Maldives, in view of its characteristics, was admitted as a member Pacific POPIN subregional network only in principle.[67] The Hirschman–Herfindahl index of the United Nations Economic and Social Commission for Asia and the Pacific for the region includes only the original seven signatories of SAARC.[68]

text: The British Indian Ocean Territory is connected to the region by a publication of Jane's for security considerations.[69] The region may also include the disputed territory of Aksai Chin, which was part of the British Indian princely state of Jammu and Kashmir, but is now administered as part of the Chinese autonomous region of Xinjiang.[70]

text: The inclusion of Myanmar in South Asia is without consensus, with many considering it a part of Southeast Asia and others including it within South Asia.[18][27] Afghanistan was of importance to the British colonial empire, especially after the Second Anglo-Afghan War over 1878–1880. Afghanistan remained a British protectorate until 1919, when a treaty with Vladimir Lenin included the granting of independence to Afghanistan. Following India's partition, Afghanistan has generally been included in South Asia, with some considering it a part of Southwest Asia.[16] During the Soviet war in Afghanistan (1979–1989) American foreign policy considered Pakistan and Afghanistan in Southwest Asia, while others included it as a part of South Asia.[7] There is no universal agreement among scholars on which countries should be included within South Asia.[18]

text: In the past, a lack of a coherent definition for South Asia resulted in not only a lack of academic studies, but also in a lack interest for such studies.[71] The confusion existed also because of the lack of a clear boundary – geographically, geopolitical, socio-culturally, economically or historically – between South Asia and other parts of Asia, especially the Middle East and Southeast Asia.[72] Identification with a South Asian identity was also found to be significantly low among respondents in an older two-year survey across Bangladesh, India, Nepal, Pakistan, and Sri Lanka.[73] However, modern definitions of South Asia are very consistent in including Afghanistan, India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan and Maldives as the constituent countries.[21][22][23][24][25][26]

text: Indian subcontinent[edit]

text: According to the Oxford English Dictionary, the term "subcontinent" signifies a "subdivision of a continent which has a distinct geographical, political, or cultural identity" and also a "large land mass somewhat smaller than a continent".[74][75] Historians Catherine Asher and Cynthia Talbot state that the term "Indian subcontinent" describes a natural physical landmass in South Asia that has been relatively isolated from the rest of Eurasia.[76] The Indian subcontinent is also a geological term referring to the land mass that drifted northeastwards from ancient Gondwana, colliding with the Eurasian plate nearly 55 million years ago, towards the end of Palaeocene. This geological region largely includes Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka.[77]

text: The use of the term Indian subcontinent began in the British Empire, and has been a term particularly common in its successors.[78] This region has also been labelled as "India" (in its classical and pre-modern sense), "Greater India", or as South Asia.[27][43]

text: According to anthropologist John R. Lukacs, "the Indian Subcontinent occupies the major landmass of South Asia",[79] while the political science professor Tatu Vanhanen states, "the seven countries of South Asia constitute geographically a compact region around the Indian Subcontinent".[80] According to Chris Brewster, India, Pakistan, Bangladesh, Sri Lanka, Nepal and Bhutan constitute the Indian subcontinent; with Afghanistan and Maldives included it is more commonly referred to as South Asia.[81] The geopolitical boundaries of Indian subcontinent, according to Dhavendra Kumar, include "India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan and other small islands of the Indian Ocean".[82] Maldives, the country consisting of a small archipelago southwest of the peninsula, is considered part of the Indian subcontinent.[83]

text: The terms "Indian subcontinent" and "South Asia" are sometimes used interchangeably.[30][78] The South Asia term is particularly common when scholars or officials seek to differentiate this region from East Asia.[84] According to historians Sugata Bose and Ayesha Jalal, the Indian subcontinent has come to be known as South Asia "in more recent and neutral parlance."[85] This "neutral" notion refers to the concerns of Pakistan and Bangladesh, particularly given the recurring conflicts between India and Pakistan, wherein the dominant placement of "India" as a prefix before the subcontinent might offend some political sentiments.[27]

text: There is no globally accepted definition on which countries are a part of South Asia or Indian subcontinent.[18][19][20] While Afghanistan is not considered as a part of the Indian subcontinent, Afghanistan is often included in South Asia.[20] Similarly, Myanmar is included by some scholars in South Asia but not in Indian subcontinent.[27]

text: History[edit]

text: Ancient era[edit]

text: The history of core South Asia begins with evidence of human activity of Homo sapiens, as long as 75,000 years ago, or with earlier hominids including Homo erectus from about 500,000 years ago.[86] The Indus Valley Civilization, which spread and flourished in the northwestern part of South Asia from c. 3300 to 1300 BCE in present-day Northern India, Pakistan and Afghanistan, was the first major civilization in South Asia.[87] A sophisticated and technologically advanced urban culture developed in the Mature Harappan period, from 2600 to 1900 BCE.[88]

text: The earliest prehistoric culture have roots in the mesolithic sites as evidenced by the rock paintings of Bhimbetka rock shelters dating to a period of 30,000 BCE or older,[note 2] as well as neolithic times.[note 3] According to anthropologist Possehl, the Indus Valley Civilization provides a logical, if somewhat arbitrary, starting point for South Asian religions, but these links from the Indus religion to later-day South Asian traditions are subject to scholarly dispute.[89]

text: The Vedic period, named after the Vedic religion of the Indo-Aryans,[note 4] lasted from c. 1900 to 500 BCE.[91][92] The Indo-Aryans were pastoralists[93] who migrated into north-western India after the collapse of the Indus Valley Civilization,[90][94] Linguistic and archaeological data show a cultural change after 1500 BCE,[90] with the linguistic and religious data clearly showing links with Indo-European languages and religion.[95] By about 1200 BCE, the Vedic culture and agrarian lifestyle was established in the northwest and northern Gangetic plain of South Asia.[93][96][97] Rudimentary state-forms appeared, of which the Kuru-Pañcāla union was the most influential.[98][99] The first recorded state-level society in South Asia existed around 1000 BCE.[93] In this period, states Samuel, emerged the Brahmana and Aranyaka layers of Vedic texts, which merged into the earliest Upanishads.[100] These texts began to ask the meaning of a ritual, adding increasing levels of philosophical and metaphysical speculation,[100] or "Hindu synthesis".[101]

text: Increasing urbanisation of India between 800 and 400 BCE, and possibly the spread of urban diseases, contributed to the rise of ascetic movements and of new ideas which challenged the orthodox Brahmanism.[102] These ideas led to Sramana movements, of which Mahavira (c. 549–477 BCE), proponent of Jainism, and Buddha (c. 563-483), founder of Buddhism, were the most prominent icons.[103]

text: The Greek army led by Alexander the Great stayed in the Hindu Kush region of South Asia for several years and then later moved into the Indus valley region. Later, the Maurya Empire extended over much of South Asia in the 3rd century BCE. Buddhism spread beyond the Indian subcontinent, through northwest into Central Asia. The Bamiyan Buddhas of Afghanistan and the edicts of Aśoka suggest that the Buddhist monks spread Buddhism (Dharma) in eastern provinces of the Seleucid Empire, and possibly even farther into West Asia.[104][105][106] The Theravada school spread south from India in the 3rd century BCE, to Sri Lanka, later to Southeast Asia.[107] Buddhism, by the last centuries of the 1st millennium BCE, was prominent in the Himalayan region, Gandhara, Hindu Kush region and Bactria.[108][109][110]

text: From about 500 BCE through about 300 CE, the Vedic-Brahmanic synthesis or "Hindu synthesis" continued.[101] Classical Hindu and Sramanic (particularly Buddhist) ideas spread within Indian subcontinent, as well outside South Asia.[111][112][113] The Gupta Empire ruled over a large part of the subcontinent between 4th and 7th centuries, a period that saw the construction of major temples, monasteries and universities such as the Nalanda.[114][115][116] During this era, and through the 10th century, numerous cave monasteries and temples such as the Ajanta Caves, Badami cave temples and Ellora Caves were built in South Asia.[117][118][119]

text: Medieval era[edit]

text: Islam came as a political power in the fringe of South Asia in 8th century CE when the Arab general Muhammad bin Qasim conquered Sindh and Multan in southern Punjab in modern-day Pakistan.[120] By 962 CE, Hindu and Buddhist kingdoms in South Asia were under a wave of raids from Muslim armies from Central Asia.[121] Among them was Mahmud of Ghazni, who raided and plundered kingdoms in north India from east of the Indus river to west of Yamuna river seventeen times between 997 and 1030.[122] Mahmud of Ghazni raided the treasuries but retracted each time, only extending Islamic rule into western Punjab.[123][124]

text: The wave of raids on north Indian and western Indian kingdoms by Muslim warlords continued after Mahmud of Ghazni, plundering and looting these kingdoms.[125] The raids did not establish or extend permanent boundaries of their Islamic kingdoms. The Ghurid Sultan Mu'izz al-Din Muhammad began a systematic war of expansion into north India in 1173.[126] He sought to carve out a principality for himself by expanding the Islamic world.[122][127] Mu'izz sought a Sunni Islamic kingdom of his own extending east of the Indus river, and he thus laid the foundation for the Muslim kingdom that became the Delhi Sultanate.[122] Some historians chronicle the Delhi Sultanate from 1192 due to the presence and geographical claims of Mu'izz al-Din in South Asia by that time.[128] The Delhi Sultanate covered varying parts of South Asia, and was ruled by a series of dynasties, called Mamluk, Khalji, Tughlaq, Sayyid and Lodi dynasties. Muhammad bin Tughlaq came to power in 1325, launched a war of expansion and the Delhi Sultanate reached it largest geographical reach over the Indian subcontinent during his 26-year rule.[129] A Sunni Sultan, Muhammad bin Tughlaq persecuted non-Muslims such as Hindus, as well as non-Sunni Muslims such as Shia and Mahdi sects.[130][131][132]

text: Revolts against the Delhi Sultanate sprang up in many parts of South Asia during the 14th century. After the death of Muhammad bin Tughlaq, the Bengal Sultanate came to power in 1352 CE, as the Delhi Sultanate began disintegrating. The Bengal Sultanate remained in power through the early 16th century. It was reconquered by the armies of the Mughal Empire. The state religion of the Bengal Sultanate was Islam, and the region under its rule, a region that ultimately emerged as the modern nation of Bangladesh, saw a growth of a syncretic form of Islam.[133][134] In the Deccan region, the Hindu kingdom Vijayanagara Empire came to power in 1336 and remained in power through the 16th century, after which it too was reconquered and absorbed into the Mughal Empire.[135][136]

text: About 1526, the Punjab governor Dawlat Khan Lodī reached out to the Mughal Babur and invited him to attack Delhi Sultanate. Babur defeated and killed Ibrahim Lodi in the Battle of Panipat in 1526. The death of Ibrahim Lodi ended the Delhi Sultanate, and the Mughal Empire replaced it.[137]

text: Modern era[edit]

text: The modern history period of South Asia, that is 16th-century onwards, witnessed the start of the Central Asian dynasty named the Mughals, with Turkish-Mongol roots and Sunni Islam theology. The first ruler was Babur, whose empire extended the northwest and Indo-Gangetic Plain regions of South Asia. The Deccan and northeastern region of the South Asia was largely under Hindu kings such as those of Vijayanagara Empire and Ahom kingdom,[138] with some regions such as parts of modern Telangana and Andhra Pradesh under local Sultanates such as the Shia Islamic rulers of Golconda Sultanate.[139]

text: The Mughal Empire continued its wars of expansion after Babur's death. With the fall of Rajput kingdoms and Vijayanagara, its boundaries reached all of west, as well as the Marathi and Kannada speaking regions of the Deccan peninsula. The Mughal Empire was marked by a period of artistic exchanges and a Central Asian and South Asian architecture synthesis, with remarkable buildings such as the Taj Mahal.[140] It also marked an extended period of religious persecution.[141] Two of the religious leaders of Sikhism, Guru Arjan and Guru Tegh Bahadur were arrested under orders of the Mughal emperors, asked to convert to Islam, and executed when they refused.[142][143][144] Religious taxes on non-Muslims called jizya were imposed. Buddhist, Hindu and Sikh temples were desecrated. However, not all Muslim rulers persecuted non-Muslims. Akbar, a Mughal ruler for example, sought religious tolerance and abolished jizya.[145] After his death, the persecution of non-Muslims in South Asia returned.[146] The persecution and religious violence in South Asia peaked during Aurangzeb era, with him issuing orders in 1669, to all his governors of provinces to "destroy with a willing hand the schools and temples of the infidels, and that they were strictly enjoined to put an entire stop to the teaching and practice of idolatrous forms of worship".[147][148] In Aurangzeb's time, almost all of South Asia was claimed by the Mughal Empire. However, this claim was violently challenged in various regions of South Asia, particularly by the Sikh Guru Gobind Singh in the northwest,[149] and by Shivaji in the Deccan regions.[150]

text: Maritime trading between South Asia and European merchants began after the Portuguese explorer Vasco de Gama returned to Europe. After the death of Aurangzeb and the collapse of the Mughal Empire, the region came under the rule of many small Islamic sultanates and Hindu kingdoms. British, French, Portuguese colonial interests struck treaties with these rulers, and established their trading ports. In the northwest South Asia, a large region was consolidated into the Sikh Empire by Ranjit Singh.[151][page needed][152] After his death, the British Empire expanded their interests till the Hindu Kush region. In the east, the Bengal region was split into Muslim East Bengal and Hindu West Bengal, by the colonial British empire, in early 1900s, a split that was reversed. However, after the World War II, at the eve of India's independence, the region was split again into East Pakistan and West Bengal. East Pakistan became Bangladesh in 1971.[153][154]

text: Geography[edit]

text: According to Saul Cohen, early colonial era strategists treated South Asia with East Asia, but in reality the South Asia region excluding Afghanistan is a distinct geopolitical region separated from other nearby geostrategic realms, one that is geographically diverse.[155] The region is home to a variety of geographical features, such as glaciers, rainforests, valleys, deserts, and grasslands that are typical of much larger continents. It is surrounded by three water bodies – the Bay of Bengal, the Indian Ocean and the Arabian Sea – and has acutely varied climate zones. The tip of the Indian Peninsula had the highest quality pearls.[156]

text: Boundary[edit]

text: The boundaries of South Asia vary based on how the region is defined. South Asia's northern, eastern, and western boundaries vary based on definitions used, while the Indian Ocean is the southern periphery. Most of this region rests on the Indian Plate and is isolated from the rest of Asia by mountain barriers.[157][158] Much of the region consists of a peninsula in south-central Asia, rather resembling a diamond which is delineated by the Himalayas on the north, the Hindu Kush in the west, and the Arakanese in the east,[159] and which extends southward into the Indian Ocean with the Arabian Sea to the southwest and the Bay of Bengal to the southeast.[30][32]

text: According to Robert M. Cutler – a scholar of Political Science at Carleton University,[160] the terms South Asia, Southwest Asia and Central Asia are distinct, but the confusion and disagreements have arisen due to the geopolitical movement to enlarge these regions into Greater South Asia, Greater Southwest Asia and Greater Central Asia. The frontier of Greater South Asia, states Cutler, between 2001–2006 has been geopolitically extended to eastern Iran and western Afghanistan in the west, and in the north to northeastern Iran, northern Afghanistan, and southern Uzbekistan.[160]

text: Indian plate[edit]

text: Most of this region is a subcontinent resting on the Indian Plate, the northerly portion of the Indo-Australian Plate, separated from the rest of the Eurasian Plate. The Indian Plate includes most of South Asia, forming a land mass which extends from the Himalayas into a portion of the basin under the Indian Ocean, including parts of South China and Eastern Indonesia, as well as Kunlun and Karakoram ranges,[161][162][163][page needed] and extending up to but not including Ladakh, Kohistan, the Hindu Kush range and Balochistan.[164][165][166] It may be noted that geophysically the Yarlung Tsangpo River in Tibet is situated at the outside of the border of the Subcontinental structure, while the Pamir Mountains in Tajikistan are situated inside that border.[167]

text: It was once a small continent before colliding with the Eurasian Plate about 50–55 million years ago and giving birth to the Himalayan range and the Tibetan plateau. It is the peninsular region south of the Himalayas and Kuen Lun mountain ranges and east of the Indus River and the Iranian Plateau, extending southward into the Indian Ocean between the Arabian Sea (to the southwest) and the Bay of Bengal (to the southeast).

text: Climate[edit]

text: The climate of this vast region varies considerably from area to area from tropical monsoon in the south to temperate in the north. The variety is influenced by not only the altitude, but also by factors such as proximity to the sea coast and the seasonal impact of the monsoons. Southern parts are mostly hot in summers and receive rain during monsoon periods. The northern belt of Indo-Gangetic plains also is hot in summer, but cooler in winter. The mountainous north is colder and receives snowfall at higher altitudes of Himalayan ranges.

text: As the Himalayas block the north-Asian bitter cold winds, the temperatures are considerably moderate in the plains down below. For most part, the climate of the region is called the Monsoon climate, which keeps the region humid during summer and dry during winter, and favours the cultivation of jute, tea, rice, and various vegetables in this region.

text: South Asia is largely divided into four broad climate zones:[169]

text:
The northern Indian edge and northern Pakistani uplands have a dry subtropical continental climate
The far south of India and southwest Sri Lanka have a equatorial climate
Most of the peninsula have a tropical climate with variations:

Hot subtropical climate in northwest India
Cool winter hot tropical climate in Bangladesh
Tropical semi-arid climate in the center

The Himalayas have an Alpine climate

text: Maximum relative humidity of over 80% has been recorded in Khasi and Jaintia Hills and Sri Lanka, while the area adjustment to Pakistan and western India records lower than 20%–30%.[169] Climate of South Asia is largely characterized by monsoons. South Asia depends critically on monsoon rainfall.[170] Two monsoon systems exist in the region:[171]

text:
The summer monsoon: Wind blows from southwest to most of parts of the region. It accounts for 70%–90% of the annual precipitation.
The winter monsoon: Wind blows from northeast. Dominant in Sri Lanka and Maldives.

text: The warmest period of the year precedes the monsoon season (March to mid June). In the summer the low pressures are centered over the Indus-Gangetic Plain and high wind from the Indian Ocean blows towards the center. The monsoons are second coolest season of the year because of high humidity and cloud covering. But, at the beginning of June the jetstreams vanish above the Tibetan Plateau, low pressure over the Indus Valley deepens and the Intertropical Convergence Zone (ITCZ) moves in. The change is violent. Moderately vigorous monsoon depressions form in the Bay of Bengal and make landfall from June to September.[169]

text: Statistical data[edit]

text:
Country
[172][172][173][174]
Capital
[174][175][176]
Area
(km2)
[177]
Population
(2017)[178]
Density
(per km2)
Nominal GDP
(2017)[179]
GDP per capita
(2017)[180]

HDI
(2016)[181]

 Afghanistan
Kabul
652,864
34,169,169
53.3
$20.57 billion
$559
0.479

 Bangladesh
Dhaka
147,570
164,827,718
1,116.6
$248.85 billion
$1,520
0.579

 Bhutan
Thimphu
38,394
792,877
20.6
$2.31 billion
$2,870
0.607

 India
New Delhi
3,287,263
1,342,512,706
408.4
$2.450 trillion
$1,850
0.624

 Maldives
Malé
298
375,867
1,261.3
$3.58 billion
$9,950
0.701

   Nepal
Kathmandu
147,181
29,187,037
198.3
$24.64 bilion
$866
0.558

 Pakistan
Islamabad
881,913
207,774,520
223.1
$304.4 billion
$1,629
0.550

 Sri Lanka
Colombo
65,610
20,905,335
318.6
$84.02 billion
$3,930
0.766

Total
5,221,093
1,800,545,229
-
-
-
-

text: Past and Future Population[edit]

text:
Main article: List of countries by past and future population

Main article: List of countries by future population (United Nations, medium fertility variant)

List of countries by past and future population provide 1950, 2000 and 2050 population while List of countries by future population (United Nations, medium fertility variant) provide 2100 population.

text:
Rank
Country
Area
1950
2000
2050
2100

1
 India
3,287,263
369,881,000
1,006,301,000
1,656,554,000
1,659,786,000

2
 Pakistan
881,913
40,383,000
152,430,000
300,848,000
364,283,000

3
 Bangladesh
147,570
45,646,000
132,151,000
201,249,000
169,541,000

4
 Afghanistan
652,864
8,151,000
22,462,000
63,796,000
57,638,000

5
   Nepal
147,181
8,990,000
24,819,000
45,985,000
29,677,000

6
 Sri Lanka
65,610
7,534,000
19,042,000
25,167,000
14,857,000

7
 Bhutan
38,394
164,000
606,000
952,000
793,000

8
 Maldives
298
80,000
300,000
445,000
438,000

Total
5,221,093
480,829,000
1,358,111,000
2,294,996,000
2,297,013,000

text: Land and Water Area[edit]

text:
Main article: Exclusive economic zone

Main article: Indian Ocean

text: This list includes dependent territories within their sovereign states (including uninhabited territories), but does not include claims on Antarctica. EEZ+TIA is exclusive economic zone (EEZ) plus total internal area (TIA) which includes land and internal waters.

text:
Rank
Country
Area
EEZ
Shelf
EEZ+TIA

1
 India
3,287,263
2,305,143
402,996
5,592,406

2
 Pakistan
881,913
290,000
51,383
1,117,911

3
 Bangladesh
147,570
86,392
66,438
230,390

4
 Afghanistan
652,864
0
0
652,864

5
   Nepal
147,181
0
0
147,181

6
 Sri Lanka
65,610
532,619
32,453
598,229

7
 Bhutan
38,394
0
0
38,394

8
 Maldives
298
923,322
34,538
923,622

Total
5,221,093
4,137,476
587,808
9,300,997

text: Regional groups of countries[edit]

text:
Name of country/region, with flag
Area
(km2)
Population
Population density
(per km2)
Capital or Secretariat
Currency
Countries included
Official languages
Coat of Arms

Core Definition (above) of South Asia
5,220,460
1,726,907,000
330.79
N/A
N/A
Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka
N/A
N/A

UNSD of South Asia
6,778,083
1,702,000,000
270.77
N/A
N/A
Afghanistan, Bangladesh, Bhutan, India, Iran, Maldives, Nepal, Pakistan, Sri Lanka
N/A
N/A

SAARC
4,637,469
1,626,000,000
350.6
Kathmandu
N/A
Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka
English
N/A

BBIN
3,499,559
1,465,236,000
418.69
N/A
N/A
Bangladesh, Bhutan, India, Nepal
N/A
N/A

SASEC
3,565,467
1,485,909,931
416.75
N/A
N/A
Bangladesh, Bhutan, India, Nepal, Sri Lanka, Maldives
N/A
N/A

text: Demographics[edit]

text: The population of South Asia is about 1.749 billion which makes it the most populated region in the world.[182] It is socially very mixed, consisting of many language groups and religions, and social practices in one region that are vastly different from those in another.[183]

text: Largest urban areas[edit]

text: South Asia is home to some of the most populated cities in the world. Delhi, Karachi, Mumbai, and Dhaka are four of the world's largest megacities.

text:
Rank
City
Province/State
Country
Population[184]
Area (km2)[184]
Density (/km2)[184]
Classification

1
Delhi
National Capital Region
 India
24,998,000
2,072
12,100
Capital region

2
Karachi
Sindh
 Pakistan
24,300,000[185][186]
945
23,400
Metropolis

3
Mumbai
Maharashtra
 India
17,712,000
546
32,400
Megacity

4
Dhaka
Dhaka Division
 Bangladesh
15,669,000
360
43,500
City corporation

5
Kolkata
West Bengal
 India
14,667,000
1,204
12,200
Megacity

6
Lahore
Punjab
 Pakistan
10,052,000
790
12,700
Metropolis

7
Bengaluru
Karnataka
 India
9,807,000
1,116
8,400
Metropolis

8
Chennai
Tamil Nadu
 India
9,714,000
375
25,900
Metropolis

9
Hyderabad
Telangana
 India
8,754,000
971
10,000
Metropolis

10
Ahmedabad
Gujarat
 India
7,186,000
464
20,600
Metropolis

text: Languages[edit]

text: There are numerous languages in South Asia. The spoken languages of the region are largely based on geography and shared across religious boundaries, but the written script is sharply divided by religious boundaries. In particular, Muslims of South Asia such as in Afghanistan and Pakistan use the Arabic alphabet and Persian Nastaliq. Till 1971, Muslim Bangladesh (then known as East Pakistan) too mandated only the Nastaliq script, but thereafter has adopted regional scripts and particularly Bengali. Non-Muslims of South Asia, and some Muslims in India, on the other hand use their traditional ancient heritage scripts such as those derived from Brahmi script for Indo-European languages and non-Brahmi scripts for Dravidian languages and others.[187]

text: The Nagari script has been the primus inter pares of the traditional South Asian scripts.[188] The Devanagari script is used for over 120 South Asian languages,[189] including Hindi,[190] Marathi, Nepali, Pali, Konkani, Bodo, Sindhi and Maithili among other languages and dialects, making it one of the most used and adopted writing systems in the world.[191] The Devanagari script is also used for classical Sanskrit texts.[189]

text: The largest spoken language in this region is Hindi, followed by Bengali, Telugu, Marathi, Gujarati and Punjabi.[187] In the modern era, new syncretic languages developed in the region such as Urdu that is used by Muslim community of northern Indian subcontinent (particularly Pakistan and northern states of India).[192] The Punjabi language spans three religions: Islam, Hinduism and Sikhism. The spoken language is similar, but it is written in three scripts. The Sikh use Gurmukhi alphabet, Muslim Punjabis in Pakistan use the Nastaliq script, while Hindu Punjabis in India use the Gurmukhi or Nāgarī script. The Gurmukhi and Nagari scripts are distinct but close in their structure, but the Persian Nastaliq script is very different.[193]

text: English, with British spelling, is commonly used in urban areas and is a major economic lingua franca of South Asia.[194]

text: Religions[edit]

text: In 2010, South Asia had the world's largest population of Hindus, Jains and Sikhs,[12] about 510 million Muslims,[12] as well as over 25 million Buddhists and 35 million Christians.[14] Hindus make up about 68 percent or about 1 billion and Muslims at 31 percent or 510 million of the overall South Asia population,[195][196] while Buddhists, Jains, Christians and Sikhs constitute most of the rest. The Hindus, Buddhists, Jains, Sikhs and Christians are concentrated in India, Nepal, Sri Lanka and Bhutan, while the Muslims are concentrated in Afghanistan (99%), Bangladesh (90%), Pakistan (96%) and Maldives (100%).[12]

text: Indian religions are the religions that originated in the Indian subcontinent; namely Hinduism, Jainism, Buddhism and Sikhism.[197] The Indian religions are distinct yet share terminology, concepts, goals and ideas, and from the Indian subcontinent spread into East Asia and southeast Asia.[197] Early Christianity and Islam were introduced into coastal regions of South Asia by merchants who settled among the local populations. Later Sindh, Balochistan, and parts of the Punjab region saw conquest by the Arab caliphates along with an influx of Muslims from Persia and Central Asia, which resulted in spread of both Shia and Sunni Islam in parts of northwestern region of South Asia. Subsequently, under the influence of Muslim rulers of the Islamic sultanates and the Mughal Empire, Islam spread in South Asia.[198][199]

text:
Afghanistan[200]
Islam (99%), Hinduism, Sikhism and Christianity (1%)

Bangladesh[201]
Islam (90%), Hinduism (9%), Buddhism (0.6%), Christianity (0.3%), Others (0.1%)

Bhutan[202]
Buddhism (75%), Hinduism (25%)

India[202][203]
Hinduism (79.8%), Islam (14.5%), Christianity (2.3%), Sikhism (1.7%), Buddhism (0.7%), Jainism (0.4%), Others (0.9%)

Maldives[204]
Sunni Islam (100%) (One must be a Sunni Muslim to be a citizen on the Maldives[205][206])

Nepal[207]
Hinduism (82%), Buddhism (9.0%), Islam (4.4%), Kirat (3.1%), Christianity (1.4%), Others (0.8%)

Pakistan[208]
Islam (96.28%), Hinduism (2%), Christianity (1.59%), Ahmaddiyya (0.22%)

Sri Lanka[209]
Buddhism (70.19%), Hinduism (12.61%), Islam (9.71%), Christianity (7.45%).

text: Economy[edit]

text: India is the largest and fastest growing economy in the region (US$2.180 trillion) and makes up almost 82% of the South Asian economy; it is the world's 7th largest in nominal terms and 3rd largest by purchasing power adjusted exchange rates (US$8.020 trillion).[210] India is the only member of powerful G-20 major economies and BRICS from the region. It is the fastest growing major economy in the world and one of the world's fastest registering a growth of 7.3% in FY 2014–15. Pakistan has the next largest economy($304.3 billion) and the 5th highest GDP per capita in the region,[211] followed by Bangladesh and then by Sri Lanka which has the 2nd highest per capita and is the 4th largest economy in the region. According to a World Bank report in 2015, driven by a strong expansion in India, coupled with favorable oil prices, from the last quarter of 2014 South Asia become the fastest-growing region in the world[212]

text: The Major Market stock exchanges in the region are Bombay Stock Exchange (BSE) with market Capitalization of $1.68 trillion (11th largest in the world), National Stock Exchange of India (NSE) with market capitalization of $1.64 trillion (12th largest in the world), and Karachi Stock Exchange with market capitalization of $60 billion.[213]

text: Economic data is sourced from the International Monetary Fund, current as of April 2017, and is given in US dollars.[214]

text:
Country
[172][172][173][174]
Currency
Population
(2017)[178]
Nominal GDP
(2017)[179]
GDP per capita
(2017)[180]

GDP growth
(2017)[215]

Inflation
(2017)[216]

 Afghanistan
؋ Afghani
34,169,169
$20.57 billion
$559
3%
6%

 Bangladesh
৳ Taka
164,827,718
$248.85 billion
$1,520
6.9%
6.4%

 Bhutan
Nu. Ngultrum
792,877
$2.31 billion
$2,870
5.9%
4.1%

 India
₹ Rupee
1,342,512,706
$2.450 trillion
$1,850
7.2%
4.8%

 Maldives
ރ Rufiyaa
375,867
$3.58 billion
$9,950
4.1%
2.5%

   Nepal
रु Rupee
29,187,037
$24.64 billion
$865
7.7%
6.7%

 Pakistan
₨ Rupee
207,774,520
$304.4 billion
$1,629
5%
4.3%

 Sri Lanka
රු/ரூ Rupee
20,905,335
$84.02 billion
$3,930
4.5%
5.8%

text: Health and nutrition[edit]

text:
Afghanistan
Bangladesh
Bhutan
India
Maldives
Nepal
Pakistan
Sri Lanka

Population undernourished (2015)[217]
26.8%
16.4%
N/A
15.2%
5.2%
7.8%
22%
22%

Population below poverty line (CIA Factbook)[218]
35.8%
31.5%
12%
29.8%
16%
25.2%
22.3%
8.9%

text: According to WHO, South Asia is home to two out of the three countries in the world still affected by polio, Pakistan and Afghanistan, with 306 & 28 polio cases registered in 2014 respectively.[219] Attempts to eradicate polio have been badly hit by opposition from militants in both countries, who say the program is cover to spy on their operations. Their attacks on immunization teams have claimed 78 lives since December 2012.[220]

text: According to the World Bank's 2011 report, based on 2005 ICP PPP, about 24.6% of the South Asian population falls below the international poverty line of $1.25/day.[221] Afghanistan and Bangladesh rank the highest, with 30.6% and 43.3% of their respective populations below the poverty line. Bhutan, Maldives and Sri Lanka have the lowest number of people below the poverty line, with 2.4%, 1.5% and 4.1% respectively. India has lifted the most people in the region above the poverty line between 2008 and 2011, around 140 million. As of 2011, 21.9% of India's population lives below the poverty line, compared to 41.6% in 2005.[222][223]

text: The World Bank estimates that India is one of the highest ranking countries in the world for the number of children suffering from malnutrition. The prevalence of underweight children in India is among the highest in the world, and is nearly double that of Sub Saharan Africa with dire consequences for mobility, mortality, productivity and economic growth.[224]

text: According to the World Bank, 70% of the South Asian population and about 75% of South Asia's poor live in rural areas and most rely on agriculture for their livelihood[225] according to the UN's Food and Agricultural Organisation. In 2015, approximately 281 million people in the region were malnourished. The report says that Nepal reached both the WFS target as well as MDG and is moving towards bringing down the number of undernourished people to less than 5% of the population.[217] Bangladesh reached the MDG target with the National Food Policy framework – with only 16.5% of the population undernourished. In India, the malnourished comprise just over 15 percent of the population. While the number of malnourished people in neighborhood has shown a decline over the last 25 years, the number of under-nourished in Pakistan displays an upward trend.There were 28.7 million hungry in Pakistan in the 1990s – a number that has steadily increased to 41.3 million in 2015 with 22% of the population malnourished. Approximately 194.6 million people are undernourished in India, which accounts for the highest number of people suffering from hunger in any single country.[217][226]

text: The 2006 report stated "the low status of women in South Asian countries and their lack of nutritional knowledge are important determinants of high prevalence of underweight children in the region". Corruption and the lack of initiative on the part of the government has been one of the major problems associated with nutrition in India. Illiteracy in villages has been found to be one of the major issues that need more government attention. The report mentioned that although there has been a reduction in malnutrition due to the Green Revolution in South Asia, there is concern that South Asia has "inadequate feeding and caring practices for young children".[227]

text: Governance[edit]

text:
Country
Capital
Forms of government
Head of state
Head of government
Legislature
Official language
Coat of arms/ National Emblems

 Afghanistan
Kabul
Unitary presidential Islamic republic

President

House of Elders,
House of the People
Pashto, Dari

 Bangladesh
Dhaka
Unitary parliamentary constitutional republic
President
Prime Minister
Jatiya Sangsad
Bengali

 Bhutan
Thimphu
Unitary parliamentary constitutional monarchy
King
Prime Minister
National Council, National Assembly
Dzongkha

 India
New Delhi
Federal parliamentary constitutional republic
President
Prime Minister
Rajya Sabha,
Lok Sabha
Hindi, English

 Maldives
Malé
Unitary presidential constitutional republic

President

People's Majlis
Dhivehi

   Nepal
Kathmandu
Federal parliamentary constitutional republic
President
Prime Minister
National Assembly,
House of Representatives
Nepali

 Pakistan
Islamabad
Federal parliamentary Islamic republic
President
Prime Minister
Senate,
National Assembly
Urdu, English

 Sri Lanka
Colombo
Unitary semi-presidential constitutional republic
President
Prime Minister
Parliament
Sinhalese, Tamil, English

text: Countries and territories from extended definitions[edit]

text:
Country or region
Capital
Administrative division type
Head of government
Area (km2)
Population
Official language
Coat of arms

 British Indian Ocean Territory
Diego Garcia
British Overseas Territory
Commissioner
54,400
2,500
English

 Myanmar
Naypyidaw
Unitary parliamentary constitutional republic
State Counsellor
676,578
51,486,253
Burmese

 Tibet Autonomous Region
Lhasa
Autonomous Region of China
Chairman
1,228,400
3,180,000
Tibetan, Mandarin

text: India[228][229][230] and Pakistan[231][232] are the dominant political powers in the region. India is by far the largest country in the area covering around three-fourths the land area of the subcontinent.[citation needed] India has the largest population of around three times the combined population of the 6 other countries in the subcontinent.[233] India is also the world's largest democracy[234] India's annual defence budget for 2013–14 is $39.2 Billion[235] which is equal to the whole Pakistan's Federal budget of $39.3 billion for 2014–15.[236]

text: Bangladesh is a unitary state and parliamentary democracy.[237] Bangladesh also stands out as one of the few Muslim-majority democracies. “It is a moderate and generally secular and tolerant — though sometimes this is getting stretched at the moment — alternative to violent extremism in a very troubled part of the world”, said Dan Mozena, the U.S. ambassador to Bangladesh. Although Bangladesh's legal code is secular, more citizens are embracing a conservative version of Islam, with some pushing for sharia law, analysts say. Experts say that the rise in conservatism reflects the influence of foreign-financed Islamic charities and the more austere version of Islam brought home by migrant workers in Persian Gulf countries.[238]

text: Diplomacy among the countries of South Asia has been mainly driven by populist politics, with the centre-stage taken by India-Pakistan conflict ever since their independence in 1947, and then the creation of Bangladesh under tense circumstances in 1971. During the height of Cold war, the elite political leaders of Pakistan aligned with the US, while India played crucial role in forming the Non-Aligned Movement and while maintaining goodwill relations with the USSR.

text: Pakistan's governance is one of the most conflicted in the region. The military rule and the unstable government in Pakistan has become a concern for the South Asian region. In Nepal, the governance has struggled to come in the side of democracy and it only showed signs in the recent past, basically in the 21st century, to support the democratic system. The political situation in Sri Lanka has been dominated by an increasingly assertive Sinhalese nationalism, and the emergence of a Tamil separatist movement under LTTE, which was suppressed in May 2009. Myanmar's politics is dominated by a military Junta, which has sidelined the democratic forces led by Aung San Suu Kyi.

text:
Governance and education index rankings of South Asian countries

Afghanistan
Bangladesh
Bhutan
India
Maldives
Nepal
Pakistan
Sri Lanka

Inequality-adjusted HDI (2016)[239] (global ranking of 187)
166
141
135
127
114
142
149
65

Corruption Perception Index (2016)[240] (global ranking of 168)
169
145
27
79
95
131
116
95

The Worldwide
Governance Indicators (2015)[241]

Government Effectiveness
8%
24%
68%
56%
41%
13%
27%
53%

Political stability and absence
of violence/terrorism

1%
11%
89%
17%
61%
16%
1%
47%

Rule of law
2%
27%
70%
56%
35%
27%
24%
60%

Voice and accountability
16%
31%
46%
61%
30%
33%
27%
36%

Population below poverty line (2011)[242]
35.8%
31.5%
23.7%
21.9%
16%
25.2%
21.4%
8.9%

Primary School Enrollment[243]
29%
90%
85%
92%
94%
96%
73%
98%

Secondary School Enrollment[244]
49%
54%
78%
68%
N/A
72%
38%
96%


document_title: Red blood cell

question_text: where are red blood cells produced in the body

question_tokens: where are red blood cells produced in the body

text: Red blood cell

text: Structure

text: Vertebrates

text: Almost all vertebrates, including all mammals and humans, have red blood cells. Red blood cells are cells present in blood in order to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish (family Channichthyidae); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood.[8] While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome.[9]

text: Vertebrate red blood cells consist mainly of hemoglobin, a complex metalloprotein containing heme groups whose iron atoms temporarily bind to oxygen molecules (O2) in the lungs or gills and release them throughout the body. Oxygen can easily diffuse through the red blood cell's cell membrane. Hemoglobin in the red blood cells also carries some of the waste product carbon dioxide back from the tissues; most waste carbon dioxide, however, is transported back to the pulmonary capillaries of the lungs as bicarbonate (HCO3−) dissolved in the blood plasma. Myoglobin, a compound related to hemoglobin, acts to store oxygen in muscle cells.[10]

text: The color of red blood cells is due to the heme group of hemoglobin. The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. However, blood can appear bluish when seen through the vessel wall and skin.[11] Pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Hemoglobin also has a very high affinity for carbon monoxide, forming carboxyhemoglobin which is a very bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning.

text: Having oxygen-carrying proteins inside specialized cells (as opposed to oxygen carriers being dissolved in body fluid) was an important step in the evolution of vertebrates as it allows for less viscous blood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger than capillary diameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues.[12]

text: Mammals

text: The red blood cells of mammals are typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, and a torus-shaped rim on the edge of the disk. This distinctive biconcave shape optimises the flow properties of blood in the large vessels, such as maximization of laminar flow and minimization of platelet scatter, which suppresses their atherogenic activity in those large vessels.[13] However, there are some exceptions concerning shape in the artiodactyl order (even-toed ungulates including cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells in llamas and camels (family Camelidae), tiny spherical cells in mouse deer (family Tragulidae), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (family Cervidae). Members of this order have clearly evolved a mode of red blood cell development substantially different from the mammalian norm.[7][14] Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries, as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load.[15]

text: Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. Red blood cells of mammals cells have nuclei during early phases of erythropoiesis, but extrude them during development as they mature in order to provide more space for hemoglobin. The red blood cells without nuclei, called reticulocytes, go on to lose all other cellular organelles such as their mitochondria, Golgi apparatus and endoplasmic reticulum.

text: The spleen acts as a reservoir of red blood cells, but this effect is somewhat limited in humans. In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity.

text: Human

text: A typical human red blood cell has a disk diameter of approximately 6.2–8.2 µm[16] and a thickness at the thickest point of 2–2.5 µm and a minimum thickness in the centre of 0.8–1 µm, being much smaller than most other human cells. These cells have an average volume of about 90 fL[17] with a surface of about 136 μm2, and can swell up to a sphere shape containing 150 fL, without membrane distension.

text: Adult humans have roughly 20–30 trillion red blood cells at any given time, comprising approximately 70% all cells by number.[18] Women have about 4–5 million red blood cells per microliter (cubic millimeter) of blood and men about 5–6 million; people living at high altitudes with low oxygen tension will have more. Red blood cells are thus much more common than the other blood particles: there are about 4,000–11,000 white blood cells and about 150,000–400,000 platelets per microliter.

text: Human red blood cells take on average 60 seconds to complete one cycle of circulation.[3][5][19]

text: The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin. Each human red blood cell contains approximately 270 million[citation needed] of these hemoglobin molecules. Each hemoglobin molecule carries four heme groups; hemoglobin comprises about a third of the total cell volume. Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in the blood plasma). The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body.[20][21]

text: Microstructure

text: Nucleus

text: Red blood cells in mammals anucleate when mature, meaning that they lack a cell nucleus. In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions are salamanders of the Batrachoseps genus and fish of the Maurolicus genus with closely related species.[22][23]

text: The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for the subsequent accumulation of non-coding DNA in the genome.[24] The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. In the absence of nuclear elimination, the accumulation of repeat sequences is constrained by the volume occupied by the nucleus, which increases with genome size.

text: Nucleated red blood cells in mammals consist of two forms: normoblasts, which are normal erythropoietic precursors to mature red blood cells, and megaloblasts, which are abnormally large precursors that occur in megaloblastic anemias.

text: Membrane composition

text: Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Their membrane plays many roles in this. These functions are highly dependent on the membrane composition. The red blood cell membrane is composed of 3 layers: the glycocalyx on the exterior, which is rich in carbohydrates; the lipid bilayer which contains many transmembrane proteins, besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namely phospholipids and cholesterol.[25]

text: Membrane lipids

text: The red blood cell cell membrane comprises a typical lipid bilayer, similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of cholesterol and phospholipids in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.

text: Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below:

text: Outer monolayer

text:
Phosphatidylcholine (PC);
Sphingomyelin (SM).

text: Inner monolayer

text:
Phosphatidylethanolamine (PE);
Phosphoinositol (PI) (small amounts).
Phosphatidylserine (PS);

text: This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent phospholipid transport proteins. Proteins called “Flippases” move phospholipids from the outer to the inner monolayer, while others called “floppases” do the opposite operation, against a concentration gradient in an energy dependent manner. Additionally, there are also “scramblase” proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy independent manner. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane.

text: The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons:

text:
Macrophages recognize and phagocytose red cells that expose PS at their outer surface. Thus the confinement of PS in the inner monolayer is essential if the cell is to survive its frequent encounters with macrophages of the reticuloendothelial system, especially in the spleen.
Premature destruction of thallassemic and sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.
An exposure of PS can potentiate adhesion of red cells to vascular endothelial cells, effectively preventing normal transit through the microvasculature. Thus it is important that PS is maintained only in the inner leaflet of the bilayer to ensure normal blood flow in microcirculation.
Both PS and phosphatidylinositol-4,5-bisphosphate (PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such as spectrin and protein 4.1R. Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding of protein band 4.1R to glycophorin C but decreases its interaction with protein band 3, and thereby may modulate the linkage of the bilayer to the membrane skeleton.

text: The presence of specialized structures named "lipid rafts" in the red blood cell membrane have been described by recent studies. These are structures enriched in cholesterol and sphingolipids associated with specific membrane proteins, namely flotillins, stomatins (band 7), G-proteins, and β-adrenergic receptors. Lipid rafts that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate β2-adregenic receptor signaling and increase cAMP levels, and thus regulating entry of malarial parasites into normal red cells.[26][27]

text: Membrane proteins

text: The proteins of the membrane skeleton are responsible for the deformability, flexibility and durability of the red blood cell, enabling it to squeeze through capillaries less than half the diameter of the red blood cell (7–8 μm) and recovering the discoid shape as soon as these cells stop receiving compressive forces, in a similar fashion to an object made of rubber.

text: There are currently more than 50 known membrane proteins, which can exist in a few hundred up to a million copies per red blood cell. Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. These membrane proteins can perform a wide diversity of functions, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells such as endothelial cells, as signaling receptors, as well as other currently unknown functions. The blood types of humans are due to variations in surface glycoproteins of red blood cells. Disorders of the proteins in these membranes are associated with many disorders, such as hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria.[25][26]

text: The red blood cell membrane proteins organized according to their function:

text: Transport

text:
Band 3 – Anion transporter, also an important structural component of the red blood cell cell membrane, makes up to 25% of the cell membrane surface, each red cell contains approximately one million copies. Defines the Diego Blood Group;[29]
Aquaporin 1 – water transporter, defines the Colton Blood Group;
Glut1 – glucose and L-dehydroascorbic acid transporter;
Kidd antigen protein – urea transporter;
RhAG – gas transporter, probably of carbon dioxide, defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
Na+/K+ – ATPase;
Ca2+ – ATPase;
Na+ K+ 2Cl− – cotransporter;
Na+-Cl− – cotransporter;
Na-H exchanger;
K-Cl – cotransporter;
Gardos Channel.

text: Cell adhesion

text:
ICAM-4 – interacts with integrins;
BCAM – a glycoprotein that defines the Lutheran blood group and also known as Lu or laminin-binding protein.

text: Structural role – The following membrane proteins establish linkages with skeletal proteins and may play an important role in regulating cohesion between the lipid bilayer and membrane skeleton, likely enabling the red cell to maintain its favorable membrane surface area by preventing the membrane from collapsing (vesiculating).

text:
Ankyrin-based macromolecular complex – proteins linking the bilayer to the membrane skeleton through the interaction of their cytoplasmic domains with Ankyrin.

Band 3 – also assembles various glycolytic enzymes, the presumptive CO2 transporter, and carbonic anhydrase into a macromolecular complex termed a "metabolon," which may play a key role in regulating red cell metabolism and ion and gas transport function);
RhAG – also involved in transport, defines associated unusual blood group phenotype Rhmod.

Protein 4.1R-based macromolecular complex – proteins interacting with Protein 4.1R.

Protein 4.1R – weak expression of Gerbich antigens;
Glycophorin C and D – glycoprotein, defines Gerbich Blood Group;
XK – defines the Kell Blood Group and the Mcleod unusual phenotype (lack of Kx antigen and greatly reduced expression of Kell antigens);
RhD/RhCE – defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
Duffy protein – has been proposed to be associated with chemokine clearance;[30]
Adducin – interaction with band 3;
Dematin- interaction with the Glut1 glucose transporter.

text: Surface electrostatic potential

text: The zeta potential is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes of the cell. The normal zeta potential of the red blood cell is −15.7 millivolts (mV).[31] Much of this potential appears to be contributed by the exposed sialic acid residues in the membrane: their removal results in zeta potential of −6.06 mV.

text: Function

text: Secondary functions

text: When red blood cells undergo shear stress in constricted vessels, they release ATP, which causes the vessel walls to relax and dilate so as to promote normal blood flow.[32]

text: When their hemoglobin molecules are deoxygenated, red blood cells release S-nitrosothiols, which also act to dilate blood vessels,[33] thus directing more blood to areas of the body depleted of oxygen.

text: Red blood cells can also synthesize nitric oxide enzymatically, using L-arginine as substrate, as do endothelial cells.[34] Exposure of red blood cells to physiological levels of shear stress activates nitric oxide synthase and export of nitric oxide,[35] which may contribute to the regulation of vascular tonus.

text: Red blood cells can also produce hydrogen sulfide, a signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide.[36]

text: Red blood cells also play a part in the body's immune response: when lysed by pathogens such as bacteria, their hemoglobin releases free radicals, which break down the pathogen's cell wall and membrane, killing it.[37][38]

text: Cellular processes

text: As a result of not containing mitochondria, red blood cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis of glucose and lactic acid fermentation on the resulting pyruvate.[39][40]

text: As red blood cells contain no nucleus, protein biosynthesis is currently assumed to be absent in these cells.

text: Because of the lack of nuclei and organelles, mature red blood cells do not contain DNA and cannot synthesize any RNA, and consequently cannot divide and have limited repair capabilities.[41] The inability to carry out protein synthesis means that no virus can evolve to target mammalian red blood cells.[42] However, infection with parvoviruses (such as human parvovirus B19) can affect erythroid precursors, as recognized by the presence of giant pronormoblasts with viral particles and inclusion bodies, thus temporarily depleting the blood of reticulocytes and causing anemia.[43]

text: Life cycle

text: Human red blood cells are produced through a process named erythropoiesis, developing from committed stem cells to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term infant).[44] At the end of their lifespan, they are removed from circulation. In many chronic diseases, the lifespan of the red blood cells is reduced.

text: Creation

text: Erythropoiesis is the process by which new red blood cells are produced; it lasts about 7 days. Through this process red blood cells are continuously produced in the red bone marrow of large bones. (In the embryo, the liver is the main site of red blood cell production.) The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney. Just before and after leaving the bone marrow, the developing cells are known as reticulocytes; these comprise about 1% of circulating red blood cells.

text: Functional lifetime

text: The functional lifetime of an red blood cell is about 100–120 days, during which time the red blood cells are continually moved by the blood flow push (in arteries), pull (in veins) and a combination of the two as they squeeze through microvessels such as capillaries. They are also recycled in the bone marrow.[45]

text: Senescence

text: The aging red blood cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophages and subsequent phagocytosis in the mononuclear phagocyte system (spleen, liver and lymph nodes), thus removing old and defective cells and continually purging the blood. This process is termed eryptosis, red blood cell programmed cell death.[46] This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count. Eryptosis is increased in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency, phosphate depletion, iron deficiency and Wilson's disease. Eryptosis can be elicited by osmotic shock, oxidative stress, energy depletion as well as a wide variety of endogenous mediators and xenobiotics. Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK. Inhibitors of eryptosis include erythropoietin, nitric oxide, catecholamines and high concentrations of urea.

text: Much of the resulting breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into iron (Fe3+) and biliverdin. The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin. The iron is released into the plasma to be recirculated by a carrier protein called transferrin. Almost all red blood cells are removed in this manner from the circulation before they are old enough to hemolyze. Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin, which is not excreted by the kidney.[47]

text: Clinical significance

text: Disease

text: Blood diseases involving the red blood cells include:

text: Anemias (or anaemias) are diseases characterized by low oxygen transport capacity of the blood, because of low red cell count or some abnormality of the red blood cells or the hemoglobin.

text: Iron deficiency anemia is the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed

text: Sickle-cell disease is a genetic disease that results in abnormal hemoglobin molecules. When these release their oxygen load in the tissues, they become insoluble, leading to mis-shaped red blood cells. These sickle shaped red cells are less deformable and viscoelastic meaning that they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.

text: Thalassemia is a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.

text: Hereditary spherocytosis syndromes are a group of inherited disorders characterized by defects in the red blood cell's cell membrane, causing the cells to be small, sphere-shaped, and fragile instead of donut-shaped and flexible. These abnormal red blood cells are destroyed by the spleen. Several other hereditary disorders of the red blood cell membrane are known.[48]

text: Pernicious anemia is an autoimmune disease wherein the body lacks intrinsic factor, required to absorb vitamin B12 from food. Vitamin B12 is needed for the production of hemoglobin.

text: Aplastic anemia is caused by the inability of the bone marrow to produce blood cells.

text: Pure red cell aplasia is caused by the inability of the bone marrow to produce only red blood cells.

text: Hemolysis is the general term for excessive breakdown of red blood cells. It can have several causes and can result in hemolytic anemia.

text: The malaria parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria areas, because these mutations convey some protection against the parasite.

text: Polycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood cells. The increased viscosity of the blood can cause a number of symptoms.

text: In polycythemia vera the increased number of red blood cells results from an abnormality in the bone marrow.

text: Several microangiopathic diseases, including disseminated intravascular coagulation and thrombotic microangiopathies, present with pathognomonic (diagnostic) red blood cell fragments called schistocytes. These pathologies generate fibrin strands that sever red blood cells as they try to move past a thrombus.

text: Transfusion

text: Red blood cells may be given as part of a blood transfusion. Blood may be donated from another person, or stored by the recipient at an earlier date. Donated blood usually requires screening to ensure that donors do not contain risk factors for the presence of blood-borne diseases, or will not suffer themselves by giving blood. Blood is usually collected and tested for common or serious Blood-borne diseases including Hepatitis B, Hepatitis C and HIV. The blood type (A, B, AB, or O) or the blood product is identified. This relates to the presence of antigens on the cell's surface. After this process, the blood is stored, and within a short duration is used. Blood can be given as a whole product or the red blood cells separated as packed red blood cells.

text: Blood is often transfused when there is known anaemia, active bleeding, or when there is an expectation of serious blood loss, such as prior to an operation. Before blood is given, a small sample of the recipient's blood is tested with the transfusion in a process known as cross-matching. In addition to the transmission of infection, certain types of transfusion reaction.

text: In 2008 it was reported that human embryonic stem cells had been successfully coaxed into becoming red blood cells in the lab. The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells on stromal cells from the bone marrow. It is hoped that these artificial red blood cells can eventually be used for blood transfusions.[49]

text: Tests

text: Several blood tests involve red blood cells. These include a RBC count (the number of red blood cells per volume of blood), calculation of the hematocrit (percentage of blood volume occupied by red blood cells), and the erythrocyte sedimentation rate. The blood type needs to be determined to prepare for a blood transfusion or an organ transplantation.

text: Many diseases involving red blood cells are diagnosed with a blood film (or peripheral blood smear), where a thin layer of blood is smeared on a microscope slide. This may reveal abnormalities of red blood cell shape and form. When red blood cells sometimes occur as a stack, flat side next to flat side. This is known as rouleaux formation, and it occurs more often if the levels of certain serum proteins are elevated, as for instance during inflammation.

text: Separation and blood doping

text: Red blood cells can be obtained from whole blood by centrifugation, which separates the cells from the blood plasma in a process known as blood fractionation. Packed red blood cells, which are made in this way from whole blood with the plasma removed, are used in transfusion medicine.[50] During plasma donation, the red blood cells are pumped back into the body right away and only the plasma is collected.

text: Some athletes have tried to improve their performance by blood doping: first about 1 litre of their blood is extracted, then the red blood cells are isolated, frozen and stored, to be reinjected shortly before the competition. (Red blood cells can be conserved for 5 weeks at −79 °C or −110 °F) This practice is hard to detect but may endanger the human cardiovascular system which is not equipped to deal with blood of the resulting higher viscosity. Another method of blood doping involves injection with erythropoietin in order to stimulate production of red blood cells. Both practices are banned by the World Anti-Doping Agency.

text: History

text: The first person to describe red blood cells was the young Dutch biologist Jan Swammerdam, who had used an early microscope in 1658 to study the blood of a frog.[51] Unaware of this work, Anton van Leeuwenhoek provided another microscopic description in 1674, this time providing a more precise description of red blood cells, even approximating their size, "25,000 times smaller than a fine grain of sand".

text: In 1901, Karl Landsteiner published his discovery of the three main blood groups—A, B, and C (which he later renamed to O). Landsteiner described the regular patterns in which reactions occurred when serum was mixed with red blood cells, thus identifying compatible and conflicting combinations between these blood groups. A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group—AB.

text: In 1959, by use of X-ray crystallography, Dr. Max Perutz was able to unravel the structure of hemoglobin, the red blood cell protein that carries oxygen.[52]

text: The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy of a man who died around 3255 BCE. These cells were discovered in May 2012.[53]