Junior doctors across England have launched a four-day strike in a worsening dispute over pay which threatens huge disruption to the NHS.

An estimated 350,000 appointments, including operations, will be cancelled due to the walkout by members of the British Medical Association (BMA).

Doctors mounted picket lines outside hospitals from 7am on Tuesday until Saturday morning in the longest stoppage of the wave of unrest, which has seen nurses, ambulance crews and other health workers take action since last year.

Managers have said patient care is “on a knife edge” because of the strike, while NHS Confederation chief executive Matthew Taylor said the number of appointments cancelled, previously suggested to be 250,000, was likely to rise by another 100,000.

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The strikes centre around a pay row between the BMA and Government, with the union claiming junior doctors in England have seen a 26 per cent real-terms pay cut since 2008/09 because pay rises have been below inflation.

The union has asked for a full pay restoration that the Government said would amount to a 35 per cent pay rise, which ministers have said is unaffordable.

BMA officials said the pay issue is making it harder to recruit and retain junior doctors, with members previously walking out for three days in March.

National medical director of NHS England Professor Sir Stephen Powis said on Sunday the strikes will put “immense pressures” on staff and services.

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NHS England said staff will be asked to prioritise emergency and urgent care over some routine appointments and procedures to ensure safe care for those in life-threatening situations.

The health body said appointments and operations will only be cancelled “where unavoidable” and patients will be offered alternative dates as soon as possible.

Health and Social Care Secretary Steve Barclay said: “It is extremely disappointing the BMA has called strike action for four consecutive days.

“Not only will the walkouts risk patient safety, but they have also been timed to maximise disruption after the Easter break.

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“I hoped to begin formal pay negotiations with the BMA last month but its demand for a 35 per cent pay rise is unreasonable – it would result in some junior doctors receiving a pay rise of over £20,000.

“If the BMA is willing to move significantly from this position and cancel strikes we can resume confidential talks and find a way forward, as we have done with other unions.

“People should attend appointments unless told otherwise by the NHS, continue to call 999 in a life-threatening emergency and use NHS 111 online services for non-urgent health needs.”

Asked whether people’s lives will be put at risk as a result of strike action, Dr Sumi Manirajan, deputy co-chairwoman of the British Medical Association’s junior doctors committee, told Sky News: “I can’t guarantee that no lives will be put at risk but what I can guarantee is that 500 patients are dying (every week) waiting for care at the moment.

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“What I can guarantee is that emergency care, essential care will be provided by expert clinicians in hospitals.

“So what I’m saying is that, no, I can’t guarantee that no life will be at risk this week. But that’s because lives are being put at risk every single week.”

She went on: “We were able to do our 72-hour strike safely, and that demonstrates that we do have expert clinicians who can safely step down and we do have enough doctors to cover the wards.

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“If this changes, or if there was a mass casualty event, we urge every trust to contact us because patient safety is first and foremost.”

Dr Manirajan added: “There will be patients that have their appointments and operations cancelled – the reason for this is because the Government won’t negotiate with us.

“They haven’t given us an opening offer and without an opening offer there’s nothing to negotiate.”