Figure 12.18 The HIV replication cycle.
with fever, generalised lymphadenopathy, pharyngitis,
rash, arthralgia, myalgia, diarrhoea, headache,
nausea and vomiting. This illness is clinically difficult
to distinguish from glan
Treat associated dehydration, if present, and any coexisting
infection. Often oral rehydration is safest, followed
by nutritional replacement therapy. A gradual
refeeding policy is essential initially 100 kcal/kg/day
with 3 g protein/kg/day together with
Neuropsychiatric complications: Acute withdrawal
(also known as delirium tremens) within 48 hours
may result in malaise, nausea, autonomic hyperactivity,
tremulousness, lability, insomnia, and transient
hallucinations, illusions especially
Platelets although increased in number have disrupted
function causing them to clump intravascularly leading
to thrombosis, and to fail to aggregate causing
Essential thrombocythaemia presents with bruising,
Chapter 12: Myelodysplastic and myeloproliferative disorders 483
Almost all patients have the Philadelphia chromosome, a
balanced reciprocal translocation between the long arms
of chromosomes 9 and 22 t(9;22). This result
are then removed in the spleen. Clinical problems only
become apparent when the platelet count falls below
50 109 per litre.
Children present with petechiae and superficial bruising,
however in severe cases mucosal bleeds occur such
seen in the blood film, whereas spherocytes may be
present in extravascular haemolysis. The reduced red
cell life span can be demonstrated using labelled red
Haemolysis results in an increase in red cell production
by the bone marrow, which is de
Thrombophilia is a group of disorders resulting in an
increased risk of thrombosis.
is the commonest formof thrombophilia. It is present
in 23% of the populat
problems or pain. Eye disease is treated with ganciclovir
(myelosupressive) or foscarnet (nephrotoxic)
and must be followed by maintenance therapy.
Mycobacterium tuberculosis infections are usually due
to reactivation of latent infection in the context
(see below). Patients develop vasodilation, hypotension,
bronchoconstriction and laryngeal constriction.
It is treated as for anaphylaxis (see page 499).
Any future transfusions should be with washed red
cells, autologous blood or blood from IgA deficient
Myelodysplastic syndrome, unclassified (MDS-U).
MDS associated with isolated deletion (5q).
The disorder arises from a single abnormal stem cell.
MDS is initially indolent due to inhibitory cytokines,
however over time oncogenes are ac
to chemotherapy but have a predicted median
survival 25 years.
Multiple myeloma is a malignant clonal proliferation of
3 per 100,000.
Most commonly diagnosed 6065 years.
2M : 1F
carry a worse prognosis.
Acute myeloid leukaemia
Malignant expansion of cells from the myeloid cell line.
Most common in the middle aged and elderly
Aetiology is largely unknown although previous exposure
to radiation, ben
inflammatory cytokines and causes the recruitment of
multiple cells amplifying a small specific response into a
largenon-specific reaction.This is the basis of granuloma
formation. Examples of type IV hypersensitivity include:
in factor VIII concentrates during the 1980s, recombinant
factor VIII is now the treatment of choice. About
10% of patients develop antibodies to factor VIII:c making
them very difficult to treat.
Activated partial thromboplastin time is
the development of lytic bone lesions.
An inherited coagulation disorder resulting from factor
12 in 10,000 two thirds of whom have severe disease.
Autoimmune haemolytic anaemia is subdivided according
to the temperature at which the antibodies bind to
the red cells:
Warm autoimmune haemolytic anaemia: Antibodies
bind best at 37C
Cold autoimmune haemolytic anaemia:
Polycythaemia vera (PV) is an overproduction of mature
red blood cells due to a clonal proliferation in the bone
marrow. Myeloid precursors and megakaryocytes may
also be increased.
5 per 1,000,000 population.
Most commonly presents over th
may be fine crackles or breath sounds may be normal.
Chest X-ray: The typical features are diffuse bilateral
ground glass infiltrates progressing towidespread
consolidation in severe cases (sparing of the
costophrenic angles and apices).
Down syndrome is the clinical condition usually resulting
from a trisomy of chromosome 21 first described by
Langdon Down in 1865.
Rises with increasing maternal age (1 in 3000 when
mother is less than 30 years to 1 in 3
Usually normal intelligence and life expectancy, but
deficient spatial perception, perceptual motor organisation
or fine motor execution.
Genetic karyotyping will confirm the clinical diagnosis.
Growth hormone in c
Untreated the life expectancy of an HIV infected individual
is approximately 10 years. A few individuals are
classified as long-term non-progressors with normal
CD4 counts and low viral load in the absence of treatment.
Prognosis has been dramat
oedema.Wet beriberi is rare in alcoholics.
Diagnosis is usually clinical and on response to thiamine.
Erythrocyte transketolase activity and blood pyruvate
Thiamine is replaced orally, intravenously or intramuscula
Abnormal structure of the globin chain in sickle cell
Sickle cell anaemia
Autosomal recessive condition in which there is abnormal
structure of the globin chain.
Most common haemoglobinopathy.
As HbF synthesis is normal
Endocrine disorders may be associated with the development
of obesity, such as Cushings syndrome,
hypothyroidism and polycystic ovary syndrome.
Obesity is characteristic of some congenital disorders
associated with hypogonadism, such as Prader
Figure 13.2 Heme synthesis.
Chapter 13: Metabolic disorders 515
The first enzyme, ALA synthetase is the rate-limiting
step. Enzyme deficiencies result in increases in metabolic
intermediates, which are excreted and accumulate in tissues.
This results in n
Newer therapies under evaluation include interferon,
venesection with low doses of aspirin and
anagrelide (for treatment of associated thrombocythaemia).
Themedian survival is 1020 years with treatment. 10%
of patients developmyelofibrosis on
Insufficient intake of carotenoids, especially -carotene
found in carrots and dark green leafy vegetables and
retinol found in fish oils, liver, eggs butter and cheese.
Dietary vitamin A deficiency is generally seen in the developing
Classical Reed-Sternberg cells are large cells with a pale
cytoplasm and two nuclei with prominent nucleoli said
to resemble owl eyes. There are three main types of
Nodular sclerosis which affects predominantly young