Hello, my name is Claire Sharpe.
I'm a consultant nephrologist
at King's College Hospital
and a senior lecturer
at King's College, London.
I have been interested
in Sickle cell disease in the kidney
when I've started a joint sickle cell
and kidney clinic
along with the hematologists
at King's College Hospital.
I'm going to talk a little bit
about pathophysiology of sickle cell
and kidney complications,
and talk about
the clinical manifestations.
The first person
to describe sickle cell disease
in the western literature
was James Herrick,
who was working in Boston around 1910.
He was looking after a young man
who traveled to United States
to do a dental degree.
This young man
had had a sickly childhood,
and when he arrived in America,
he was suffering with leg ulcers.
This paper very clearly describes
both the history
and the clinical examination
of this man.
And of note, James Herrick brings out
that he had increased urine volume
of low specific gravity,
a distinct trace of serum albumin.
And this very much sums up
the sickle cell nephropathy,
which we recognize
in many of our patients today.
The underlying genetic mutation
was first described in Cambridge
by Vernon Ingram in 1957.
A single point mutation
results in a replacement
to the glutamine
with a valine at the six amino acid,
and the beta-chain of adult hemoglobin.
This results in the beta hemoglobin
becoming less soluble,
particularly under hypoxic
and acidotic conditions.
This results in polymerization
of the beta hemoglobin
which can form
these rope like structures
seen here in this middle picture.
These structures make the red blood cell
rigid and undeformable
and it takes on this
characteristic sickling shape.
This polymerization sickling
is initially reversible.
However, after many cycles of sickling,
the red blood cell becomes
and then can spill over
into the peripheral circulation
that's seen on the right.
This is what James Herrick noted
and more gave the disease its name.