The lymphomas

These are malignant tumors of the lymphoreticular system

There are two main types histologically
– Hodgkin’s disease
– non Hodgkin’s lymphoma
 Hodgkin’s disease
Characterised by aggressive enlargement of the lymph nodes,
with hyperplasia, infiltration with histiocytes and lymphocytes
and the presence of characterisitc cells described by Sternberg
and Reed.

epidemiology
 rare in children (boys twice affected than girls)
 early peak of incidence in twenties, later peak in middle – age
 Clinical features
 enlargement of the cervical lymph nodes, which are painless
and rubbery
 weakness, fatigue and anorexia
 feer and seating
 pruritus
 loss of weight
 alcohol – induced pain at the site of the enlarged node
 clinical symptoms are seen in more advanced stages of the
disease (intermitent fever with drenching sweats)
 pel – Ebstein fever – consists of a few days of high pyrexia
followed by apyrexia for a few days
 symptoms due to the involvement of bone, lung, skin
 Clinical examination
 lymphadenopathy
 hepatomegaly
 splenomegaly
investigation
 normochromic, normocytic anaemia
 raised ESR
 white cells levels ↑, with eosinophilia
 hypercalcaemia
 slightly abnormal liver function
 x-ray:
 mediastinal lymphadenopathy
 pulmonary infiltration
 CT scanning of the chest and abdomen
 biopsy of a suitable node (a whole node should be removed)
Finger-warts-Hodgkins-disease
 histological classification

Four histological types of Hodgkin’s disease:

4. Lymphocyte – predominent
5. Nodular sclerosing
6. Mixed cellularity
7. Lymphocyte – depleted
 Hodgkins-disease-lymphoc

Hodgkins-diffused-
-Reed-Sternberg
Hodgkins-Marrow
 non – Hodgkin’s lymphoma

Tumor of lymporeticular tissue derived from malignant clones

of B or T cells

Presentation at extra nodal sites such as Waldayer’s ring tonsils,

adenoids and nasopharyngeal glands, the gut or skin is common
 clinical features
 lymphadenopathy
 abdominal lymph node involvement is common
 splenomegaly, hepatomegaly
 wasting, fever and sweating
 nodular infiltration of the skin

investigation
 normochromic, normocytic anaemia or a leucoerythroblastic
picture
liver tests abnormal
 bone marrow biopsy may show infiltration by lymphoid
tissue
biopsy of a lymph node from an accesible site
Lymphoma
Lymphoma
 histological classification

Two main system of pathological classification:

D. Rappaport classification:
 nodular or follicular pattern
 diffuse pattern of infiltration
E. Kiel classification:
 low grade
 high grade } malignancy
 BLEEDING DISORDERS
There is abnormal bleeding due to impairment of haemostasis
haemostasis
Injury
Factors
Exposed collagen XII + XI + VII
Serotonina
Platelet adhesion activated

Coagulation
Vasoconstriction Platelets release factors PF3
sequence
Fibrinogen
ADP Platelet prostagladin Thrombin
synthesis
Blood flow to Fibrin
Tromboxane A2
injured area reduced
Platelet aggregation
Thrombus
 bleeding disorders

haemostasis

Vascular damage

When a vessel is injured and the endothelial cell lining damaged,

the vessel constricts and platelets adhere at once to exposed
collagen.

Platelet aggregation

 at the site of injury release of substances such as nucleotides

and serotonin
enhaced by thrombin generated during coagulation
 Platelets = essential for the formation of a firm fibrin clot

Central is the activation of platelet prostaglandin synthesis

↑ aggregation

PROSTACYCLIN is synthesized by the vascular endothelial

cell and prevents platelets aggregation on the normal vascular
endothelial cell.
 Coagulation and fibrinolisis

Involves a series of enzymatic reactions soluble fibrinogen

fibrin clot
Enzymes except factor XII are serine proteases

EXTRINSEC PATHWAY: tissue factors + factor VII + calcium

ions activate factor X
INTRINSEC PATHWAY: factor XII is activated by contact
with the injured surface activates
factor XI and IX
 bleeding disorders
haemostasis
Coagulation and fibrinolisis
Activated factor IX
+ factor VIII and PF3

Activated factor IX Factor V + PF3 +

(which is the strat of a common pathway)
+ calcium ions
Tromboplastin
Calcium Trombin Prothrombin
Stabilises
Activate F XII Fibrin Activate on
fibrinogen
Coagulation is localized to the site of damage by circulating inhibitors
of Thrombin such as antithrombin III (inactivates the
serine proteases)
With the endothelial cell, via a receptor protein (thrombomodulin)
 bleeding disorders
haemostasis
Fibrinolysis

Helps to restore vessel patency (in response to vascular damage)

*
F XII activated interacts with a Kalikrein – Kinin system,
plasminogen and F XI
*
Activators from
blood and tissue Kalikrein

Plasminogen Plasmin
Proteolysis
Fibrin
Fibrin degradation
products
 bleeding disorders
investigation of bleeding disorders

 blood count and film show the number of platelets,

morphological abnormality (leukaemia)
bleeding time (BT) – useful in vascular disorders of platelet
function
 coagulation tests

The two most widely used are:

 the prothrombin time (PT)
 the partial thromboplastin time with Kaolin (PTTK)
 the prothrombin time (PT) – normal is 10-14” – used to
monitor oral anticoagulant treatment and as a coagulation and
liver function test
 the partial thromboplastin time with Kaolin (PTTK) – normal
is 30-40” – valuable for screening for possible coagulation
defects
 other tests

♦ fibrinogen and fibrin degradation products

♦ coagulation factor assays (FVIII)
♦ platelets function tests
♦ tests of the fibrinolytic system
 the purpuras
Group of disorders associated with superficial capillary
bleeding, mainly in skin and mucous membranes, due to
thrombocytopenia, platelet functional disorders or increased
capillary permeability.

Purpuric rash – consists of small purplish red spots which do not

fade on pressure.
Confluent ecchymoses

thrombocytopenic purpura
Caused by either - reduced platelet production in the marrow
- or excessive peripheral destruction of platelets
- bleeding when platelets are less than 50 000 / mmc
 causes of thrombocytopenia
– luekaemia
Marrow infiltration – tumors
– myelosclerosis
– myeloma
Impaired – chemotherapy
production Marrow damage – chemicals
– alcohol
– drugs
– aplastic anaemia
– B 12/folate deficiency
– idiophatic thrombocytopenic purpura
Immune – autoimmune haemolytic anaemia
– system lupus erythematosus drugs
–disseminated intravascular coagulation
Excessive Coagulation – thrombotic thrombocytopenic purpura
– haemolytic uraemic syndrome
destruction
Massive transfusion
– hypersplenism
Sequestration – hemangioma
 the purpuras
idiopathic thrombocytopenic purpura

 autoimmune disorder (commoner in women)

 autoantibody (lg G) to platelets is found in 70%
 sensitized platelets are removed by the reticuloendothelial
system
 antibodies cross the placenta neonatal thrombocytopenia
 clinical features
 acute form – children following a viral infection
 adults – insidiously with a purpuric rash and superficial
bruising
 epistaxis
 menorrhagia
 rarely – splenomegaly
 phisical examination is normal (expect evidence of bleeding)

investigation
 anaemia is uncommon
 thrombocytopenia (<20 000 / mmc)
 bone marrow: ↑ megakayocytes
platelets antibodies
 the purpuras
platelet functional disorders
 usually associated with excessive bruising and bleeding, and
in some acquired forms with thrombosis
 platelet count is normal or ↑
 bleeding time is prolonged
 congenital forms are rare
 acquired forms of platelet dysfunction are seen in:
 myeloproliferative disorders with morphologically
abnormal platelets
 uraemia and liver disease
 paraproteinemias which alter platelet aggregation and
adherence
 drugs (aspirin) – inhibits prostaglandin synthetase and
thereby interferes with platelet aggregation
 Von Willebrand’s disease – platelet functional impairment
caused by inherited abnormality of FVIII
 the purpuras
non – thrombocytopenic purpura
Causes
D. Congenital
♦ congenital hereditary haemorrhagic telangiectazia (Osler –
Weber – rendu disease)
♦ Ehlers – Danlos syndrome
E. Acquired
♦ severe infections (septicaemia, measles, typhoid)
♦ allergic
 Henoch – Schönlein purpura
 connective tissue disorders
♦ drugs (steroids)
♦ others
 senile purpura
 easy brusing syndrome
 paraproteinaemias
There is increased capillary permeability resulting in purpura.
 the purpuras
hereditary haemorrhagic telangiectasia

 rare disorder with autosomal dominant inheritance

 dilatation of capillaries and small arterioles produces
characteristic small red spots on the:
 skin
 nose
 mouth
 G.I. tract
 chronic G.I. bleeding is the major problem and the site of
bleeding may be hard to localize
 PURPURA DUE TO INFECTIONS
– due to damage to the vascular epithelium

easy bruising syndrome

 occurs in young women
 the purpura may be extensive
 cause – unknown
 investigations normal
 recovery spontaneous

senile purpura and purpura due to steroids

– due to atrophy of the vascular supportive tissue
 henoch – schönlein purpura

 occurs in children (usually)

 type III hypersensitivity reaction which is often preceded by
an acute infection
 widespread purpura
 abdominal pain
 haematuria and nephritis
 recovery spontaneous
 coagulation disorders
hereditary coagulation disorders

Isolated deficienties of all factors have been described, but

90% are due to factor VIII deficiency

Haemophilia A
 VIIIc depleted (VIIIc – small protein molecule with
coagulant activity)
 other component of F VIII are normal
 inherited as an X – linked trait
 the locus for this gene has been assigned to the long arm of
the X chromosome so, only males are affected
incidence 1/5000 to 1/10 000 of the population
 clinical features
 haemarthroses, often spontaneous and lead to arthritic
changes
 severe bleeding follows injury and isolated bleeding may
occur into muscles, kidney, mouth, neck

investigation
 females carriers are identified by the family history
 DNA analysis detection of carrier
 bleeding time – normal
 PT normal
 PTTK ↑
 F VIIIc ↑
 coagulation disorders
hereditary coagulation disorders
Von Willebrand’s disease

 reduced level of all the factor VIII components

 inherited as an autosomal dominant disorder affects both
sexes
 less severe than haemophilia
 haemarthroses are are
 bleeding follows minor injury or surgery
 menorrhagia and epistaxis
 bleeding time ↑
 PT normal
 PTTK ↑
 F VIII ↑
 Christmas diesease (haemophilia B)

 deficiency of F IX
 the inheritance and clinical presentation are identical to those
for haemophilia A
 incidence 10% of that of H.A.
 coagulation disorders
acquired coagulation disorders

Vitamina K deficiency

 necessary for the F II, VII, IX and X and without it factors

are unable to bind calcium and exert their coagulant function
 deficiency of vitamin K may be due to
 inadequate stores (haemorrhagic disease of the newborn or
protein – energy malnutrition)
 malabsorption of vit. K (cholestatic jaundice)
 oral anticoagulant drugs, which are vit. K antagonists
 PT and PTTK are prolonged
 bruising, haematuria and G.I. or cerebral bleeding
 Liver disease

Coagulation defects due to:

 hepatocelular damage
 cholestasis
 portal hypertension (splenomegaly hipersplenism)
 acute liver failure

Multiple transfusion syndrome

After large rapid transfusions the PT, PTTK and platelet count
should be cheked.
Rendu Osler
Heriditary-Telangiectasia
Idiopathic Thrombocytopenic Purpura
Senile Purpura
Haemarthroses-Haemophilia
DIC-purpura-fulminens
Thrombocytopenia-and-drug