Week 5 Common Conditions Flashcards
What is lymphadenopathy?
DEFINITION: the palpable enlargement (>1cm) of lymph nodes
Lymphadenitis: lymphadenopathy with pain +/- other signs of inflammation (redness, warmth)
What is the classification of lymphadenopathy?
Localised = present in 1 body area
75% of lymphadenopathies are localised
Usually reflect pathology in region of drainage
e. g. dental or tonsillar infection cervical lymphadenitis
e. g. infections in the extremities axillary or inguinal node involvement
Generalised = present in 2 (or more) non-contiguous nodal groups
25% are generalised
Generally due to significant underlying disease
e.g. glandular fever, lymphoma, leukaemia, metastatic neoplasia, HIV infection, tuberculosis
What is splenomegaly?
An important diagnostic clue
If large enough: dragging sensation in the LUQ, sensation of fullness (esp. after eating)
The storage function of the spleen is enhanced in splenomegaly
Sequestration of cellular components can lead to anaemia, leukopenia &/or thrombocytopenia
What are associated disorders of spenomegaly? (5)
Associated disorders include:
INFECTIONS
e.g. glandular fever, TB, syphilis , HIV
PORTAL HYPERTENSION
e.g. cirrhosis, cardiac failure
LYMPHOID DISORDERS
e.g. leukaemia, lymphoma, multiple myeloma
RBC DISORDERS
e.g. thalassaemia (haemolytic anaemia)
INFLAMMATORY CONDITIONS
e.g. rheumatoid arthritis, systemic lupus erythematosus
What is glandular fever?
Acute infection of B lymphocytes with Epstein-Barr Virus (EBV)
Also referred to as infectious mononucleosis
What is the incidence of glandular fever?
Most people (~90%) have had an EBV infection by the time they are adults Infection usually occurs in childhood, but is rarely symptomatic
Glandular fever (acute symptomatic infection) is common in young adults (15-35 years)
What is the transmission of glandular fever?
Usually through close personal contact - most commonly saliva
Mucosal secretions of the respiratory tract, genital tract, blood
What is the pathophysiology of glandular fever?
EBV initially infects the oropharynx, nasopharynx and salivary epithelial cells
Later extends into lymphoid tissues and B cells
ADAPTIVE IMMUNE RESPONSE
Unaffected B cells produce antibodies against EBV
Cytotoxic T cells attack virus-infected B-cells directly
Enlargement of lymphoid tissue occurs due to:
Proliferation of lymphocytes
Removal of dead and damaged B cells
What are the clinical features of glandular fever?
Long incubation period: 30-50 days
Classical symptoms: fever, sore throat, cervical lymphadenopathy, fatigue
Progression of disease: generalised lymphadenopathy, splenomegaly, hepatomegaly
Rare complications (~5%): ocular, cardiac, CNS involvement
What is the management of glandular fever?
Diagnosis of EBV infection is through serologic testing
The disease is usually self-limiting: recovery commences in a few weeks
Fatigue may last 1-2 months
Rest
Symptom relief: analgesics, antipyretics
Treatment of secondary bacterial infections Streptococcal pharyngitis occurs in 20-30% of cases Antibiotics required (penicillin or erythromycin)
What are the types of haematological cancer? (3)
Leukaemia
Proliferation of malignant leucocytes in the bone marrow
Overcrowding causes malignant cells to spill into blood
Lymphoma
Proliferation of malignant lymphocytes in lymphatic system
Formation of discrete tumours
Multiple Myeloma
Proliferation of malignant plasma cells in the bone marrow
What is the classification of leukaemia?
Based on the predominant cell of origin:
Lymphoid leukaemia
Myeloid leukaemia
Based on the degree of differentiation before the cells became malignant:
Acute leukaemia – rapid growth of immature cells (referred to as ‘blasts’)
Chronic leukaemia – slow growth of more differentiated cells
What are the types of leukaemia?
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
What is the aetiology/risk factors of leukaemia (5)?
Exact cause unknown - likely a complex interplay between environmental & genetic factors
RISK FACTORS INCLUDE:
Genetic factors
Tendency to reappear in families
Specific chromosomal abnormalities
e.g. Philadelphia Chromosome
Exposure to cigarette smoke, benzene, ionising radiation
Certain infections e.g. HIV, HCV
Chemotherapy for the treatment of lymphoma, multiple myeloma, ovarian and breast cancer
Chronic myeloid leukaemia: can develop into an acute leukaemia (‘blast crisis’) in its end-stage
What age does acute lymphoblastic leukaemia occur in? What is the prognosis?
Most common cancer of children
60% cases arise in children <14 years
PROGNOSIS
90% of children achieve complete remission
> 2/3 can be considered cured
What age does acute myeloid leukaemia occur in? What is the prognosis?
Occurs at all ages, although incidence increases w. age (>60 years)
PROGNOSIS
AML = more difficult to treat than ALL
60% of patients achieve remission
Only 15 - 30% remain free of disease at 5yrs
What are the clinical features of acute leukaemia?
Rapid onset of symptoms (Pts usually present within 3/12)
Proliferation of blast cells overcrowd bone marrow (suppresses formation of other blood cells):
Anaemia (↓ RBCs): fatigue, pallor, weakness Decreased immunity (↓ normal WBCs): fever, mouth ulcers, recurrent infections Bleeding tendencies (↓ platelets): epistaxis, purpurae, gum bleeding
Bone pain (marrow expansion) Splenomegaly, hepatomegaly, lymphadenopathy (sequestration of blasts)
Non-specific features: anorexia, weight loss, m. wasting
Nervous system infiltration: HA, vomiting, palsies, visual/auditory changes
What is the management of acute leukaemia?
DIAGNOSIS: blood marrow biopsy + blood film + clinical features
Primary aim is to achieve remission
Defined as normal bone marrow + blood + clinical status
First line: combination chemotherapy
Cytaribine – inhibits DNA synthesis
Daunorubicin – inhibits mRNA synthesis, induce DNA breakage
Vincristine – inhibits mitosis
“Curative” measures taken post-remission
Radiotherapy, prior to bone marrow transplant
Autologous vs. allogenic
What age does chronic myeloid leukaemia occur in? What is the prognosis?
Can occur at any age
Peak age for diagnosis is 50-70 yrs
Philadelphia Chromosome (BCR-ABL oncogene) present in 95% of cases
Chronic phase (2 -5 yrs): asymptomatic Accelerated phase (6-18 mth): primary symptoms Acute Blast Crisis: 3-6 mth survival
What age does chronic lymphocytic leukaemia occur in? What is the prognosis?
Most common form of adult leukaemia
90% of cases occur > 50 yrs
Usually follows an indolent course (does not require treatment in its early stages)
PROGNOSIS
Pts with early stage disease at diagnosis have a median survival of 10-15 yrs
What are the clinical features of chronic leukaemia?
Insidious onset of symptoms
Many Pts are asymptomatic & diagnosed incidentally via routine blood test (leukocytosis)
Common initial symptoms: splenomegaly, extreme fatigue, weight loss, night sweats, fever
CLL – suppression of normal antibody production is often fatal in the later stages
CML - acute blast crisis: features associated with acute leukaemia
What is the management of chronic leukaemia?
Bone marrow transplantation (usually only suitable for Pts <55 yrs)
Biological response modifiers & combination chemotherapy
Chronic Lymphocytic Leukaemia
Observation in early stages
Premature treatment can lead to poorer outcomes
Indications for treatment: progressive fatigue, symptomatic lymphadenopathy, anaemia or thrombocytopaenia
First line therapies include:
Chemotherapy – fludarabine: inhibits DNA synthesis
Antibody therapy – rituximab: destroys B lymphocytes (pictured right)
Chronic Myeloid Leukaemia
Tyrosine kinase inhibitors (e.g. imatinib) can prolong survival significantly
Tyrosine kinases are intracellular enzymes required for cellular proliferation
What is the definition of lymphoma?
discrete, malignant tumours arising in the lymphatic system
Most lymphomas arise in lymph nodes, but recall that lymphoid tissue is virtually ubiquitous in the body
Depending on the type of lymphoma, malignant cells may be found in other organs e.g. spleen, thymus, gastrointestinal tract, skin
Spread to bone marrow can occur
What is the classification of lymphoma?
Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma
What are the risk factors of lymphoma?
Family history
Certain infections
Epstein-Barr Virus, HIV, HCV, HTLV, Herpes Virus-8, H. pylori
Obesity
Adipose tissue possesses endocrine & metabolic properties
Iatrogenic immunosuppression e.g. anti-rejection therapy
Autoimmune conditions: RA, SLE
Exposure to ionizing radiation or mutagenic chemicals
What is hodgkins lymphoma?
One of the most common cancers in young adults
Usually arises in a single node or chain of related nodes
Spreads to nodes in close anatomical proximity.
Characterised by a distinctive neoplastic cell, the Reed-Sternberg (RS) cell
RS cells are large and binucleate; their presence is necessary for the diagnosis of HL
Cytokines secreted by RS cells promote tumour growth
What are the clinical features of Hodgkins lymphoma? (4)
Lymphadenopathy
Single or related group of superficial lymph nodes
Nodes are typically painless, discrete and rubbery
Cervical nodes usually affected first
Spread: occurs to adjacent nodes (esp. mediastinal)
Extranodal lymphoid involvement: uncommon
Compressive features
Occur secondary to nodal enlargement
Dysphagia, dyspnoea, engorged neck veins, neural compression
“B” symptoms
Have prognostic significance
Unexplained fever (>38C), drenching night sweats, unexplained wt loss (>10%) in preceding 6/12
Other constitutional symptoms: persistent fatigue, pruritis, anorexia
What is Non-Hodgkins lymphoma?
6th most common type of cancer in Australia
increased incidence of NHLs: attributed to increased HIV infections
Average age for diagnosis: 65
Although the disease can present at any age
The term ‘ NHL’ refers to a diverse group of disorders
B cell neoplasms (85% of tumours)
T cell & NK cell neoplasms
All types feature the neoplastic proliferation of lymphoid cells, but NOT the Reed-Sternberg form.
What are the clinical features of non-hodgkins lymphoma? (3)
Lymphadenopathy
Nodes are typically painless and discrete
Usually originate in multiple sites: cervical, axillary, inguinal and femoral nodes commonly affected first
Spread: occurs to non-contiguous nodes
Extranodal lymphoid involvement: common
Features reflect affected organs e.g. nasopharynx, GIT, bone, thyroid, testes, skin
Compressive features
Occur secondary to nodal enlargement
”B” symptoms & constitutional symptoms
Can also exist in NHL
Lymphoma vs Lymphoid Leukaemia
Used to beconsidered distinct entities, current knowledge suggests the distinction is vague
Example: chronic lymphocytic leukaemia & small lymphocytic lymphoma
Considered to have the same underlying disease process (neoplastic B cell proliferation)
Current convention is to classify the disease based upon clinical presentation:
If most cancer cells are in bone marrow + bloodstream = chronic lymphocytic leukaemia
If most cancer cells are in lymph nodes, the disease is termed small lymphocytic lymphoma
What is the management of lymphoma?
Depends on the type of lymphoma and intent of treatment (curative vs. palliative)
TREATMENTS INCLUDE
Chemotherapy
Radiotherapy
Antibody therapy
Corticosteroids
Stem cell transplant
PROGNOSIS
~75% of HL Pts can be cured
NHL: prognosis depends greatly on subtype
What is multiple myeloma?
Lymphoid malignancy of the bone marrow, characterised by the uncontrolled replication of plasma (immunoglobulin-secreting) cells
What is the incidence of multiple myeloma?
Accounts for 1.3% of all cancers in Australia
Rarely occurs before 40 yrs – peak age for diagnosis is 65
What is the aetiology of multiple myeloma?
Chromosomal mutations play a key role
Exact aetiology unknown
Risk assoc. w/ radiation exposure
Familial predisposition?
What is the pathophysiology of multiple myeloma?
Myeloma cells: neoplastic plasma cells that produce excessive amounts of abnormal antibodies (M proteins)
Result: decreased immunity, overcrowded marrow
Antibody fragments (light-chains) are also produced and accumulate in tissues and organs
Result: amyloidosis leads to renal failure
Myeloma cells form discrete tumours (plasmacytomas) within bone
Release of osteolytic cytokines destroys overlying cortical bone
Result: radiographic ‘punched-out’ lesions (1-4cm in diameter)
What are interosseous plasmacytomas? Where do they affect?
Most commonly affects the vertebral column, ribs, skull, pelvis, femur, clavicle, scapula
Risk for pathologic #
Bone marrow biopsy: abundant myeloma cells
Can comprise between 10 -90% of cells
Large potential for spread:
Lymph nodes
Other bones
Spleen, liver, kidneys lungs
What are the clinical features of multiple myeloma? (4)
Often insidious for years
Bone destruction
Bony pain, pathological #
Hypercalcaemia - confusion, weakness, lethargy, polyuria, thirst, constipation
Marrow overcrowding
Decreased immunity - recurrent infections, fever
Anaemia
Overproduction of light-chains
Deposited in kidneys as amyloid protein (toxic)
Bence-Jones proteinuria in 99% of Pts
Extraosseous plasmacytomas
What is the management of multiple myeloma?
Palliation: radiotherapy, chemotherapy
What is human immunodeficiency virus?
HIV is the pathogen responsible for acquired immunodeficiency syndrome (AIDS)
It is a retrovirus and carries its genetic material as RNA (not DNA)
The disease arose in Africa in the 1950s and has now spread throughout the world
What is the incidence of HIV?
At the end of 2016: 37 million people living with HIV worldwide, including 25, 000 Australians
HIV notification rates are highest in the 25-44 age group
Australian deaths from AIDS peaked in 1994 (953 deaths)
It has now become a chronic disease due to the advent of anti-retroviral drugs
What are the modes of transmission of HIV?
Predominantly through the exchange of body fluids (blood, semen)
Not transmitted by fomites i.e. plates, cutlery, phones, drinking fountains
Children can be infected: transplacental spread, blood spread during birth, via breast milk
Occupational exposures e.g. nurses, pathology lab technicians
Before rigorous screening measures were introduced, some contracted HIV from receiving blood transfusions or blood products
What is the pathophysiology of HIV? (Key viral enzymes & steps (5))
HIV infects and depletes immune cells which possess the CD4 glycoprotein
Predisposes life-threatening infections and malignancies
CD4 is found predominantly on T Helper (TH) lymphocytes
Other CD4+ cells: some Tc lymphocytes, NK cells, macrophages, DCs
Key viral enzymes:
protease, reverse transcriptase
Entry into cell
HIV binds to CD4 receptor and chemokine co-receptor on the host cell
Viral envelope and cell membrane fuse
HIV RNA injected into the host cell’s cytoplasm
Conversion of viral RNA
HIV RNA converted to double-stranded DNA by the viral enzyme reverse transcriptase
Viral DNA is integrated into the host cell’s DNA by the viral enzyme integrase
Dormancy
If host cell is NOT activated, viral DNA remains dormant (can be years)
Activation
If host cell is activated (by cytokines) the virus proliferates
The viral enzyme protease modifies new virions
Host cell death
Release of new virions results in host cell lysis (necrosis)
New virions free to infect other CD4-bearing (CD4+) cells
What are the stages of HIV infection?
- Acute infection
- Chronic infection
- Acquired immune deficiency syndrome
Describe stage 1 HIV (acute)
~50% of infected people experience acute illness soon after the initial exposure
Due to the sudden increase of viruses in the host
CLINICAL FEATURES
Nonspecific flu-like symptoms, including:
Fever, night sweats, fatigue, lymphadenopathy
Sore throat, headache, photophobia, myalgia, arthralgia
Diarrhoea, generalised maculopapular rash
Most symptoms subside in 1-3 weeks, although chronic lethargy, depression & irritability can persist
HIV antibodies may not be detectable for some months, however viral transmission is still possible
Describe stage 2 HIV (chronic- clinical latency)
Relatively symptom-free +/- lymphadenopathy
Can be 2 months 20 years before the onset of AIDS
The median period is 10 years
Virus multiplies but is only released sporadically
CD4+ lymphocytes gradually decrease
Describe stage 3 HIV (acquired immune deficiency syndrome)
AIDS can be diagnosed when various criteria are fulfilled
Most common diagnostic criterion met: CD4+ lymphocyte count of <200 cells/mcL
What are the clinical features of AIDS? (4)
Non-specific features
Generalised lymphadenopathy
Weight loss, wasting, nausea, fatigue, night sweats, fevers
Neurological symptoms
CNS affected more than PNS
HIV encephalopathy (AIDS dementia complex) Cognitive, behavioural, motor changes
Opportunistic infections
Candidiasis, tuberculosis, widespread herpes simplex
Rare infections
Neoplasia
e.g. non-Hodgkin’s lymphoma, Kaposi’s sarcoma
Kaposi’s sarcoma: painless, red-purple lesions (can be on any part of the body)
What is the pharmacology of HIV?
ANTI-RETROVIRAL MEDICATIONS
Used in combination to inhibit viral replication and prevent progression to AIDS
What is the management of HIV?
MAINTAIN PHYSICAL & MENTAL HEALTH: Exercise, nutritional support Cessation of nicotine, alcohol & drug use Counselling Trace past partners
POST-EXPOSURE PROPHYLAXIS
Must be implemented within 72 hours of potential exposure to HIV
Short-term (28-day course) anti-retroviral treatment
Reduces risk of seroconversion by up to 80%
Available from sexual health clinics, hospital EDs
PRE-EXPOSURE PROPHYLAXIS
Approved by Therapeutic Goods Administration, but currently not on PBS
