Miscellaneous Flashcards
What is AIDS?
Chronic potentially life threatening condition caused by HIV virus
How common is AIDS?
Mostly affects 15-24 year olds
1 in 4 people with HIV worldwide don’t know they are infected
1 million people die each year due to undiagnosed HIV
97% of people with HIV in UK are on ART
Number of new infections falling
100,000 people living with HIV at end of 2018
7,500 people were living with undiagnosed HIV infection
Epidemic is diverse
High prevalence in Central London, Rotherham, Sheffield, Manchester
How can you prevent HIV/AIDS?
Circumcision PEP - post-exposure prophylaxis PreP- pre-exposure prophylaxis Behavioural changes - condom usage STI control Vaccines Microbicides Diagnosis/partner notification HAART Screen blood products/needle exchange
What can increase your risk of getting HIV?
Men who have sex with men Heterosexual women Injecting drug users Commercial sex workers Truck drivers Migrant workers
What is acute HIV syndrome?
Within 2-4 weeks of infection but can be up to 10 months
Abrupt onset of non-specific symptoms
Severe symptoms
What is clinical latency in HIV?
No symptoms
May notice enlarged lymph nodes - persistent generalised lymphadenopathy
How does HIV infect cells?
Virus enters via mucosa
APCs to T cells a lymph nodes
Local infection within a mucosal macrophage or dendritic cell established and then spreads to other cells
Initially humoral and cell mediated responses
Level of HIV free in plasma very high around 3 weeks
Falls after this as immune response begins to fight it
T cells recover after primary infection
Eventually develop a viral reservoir that you cannot get rid of
CD4 cells begin to fall
AIDS when CD4 < 200
How does the virus replicate within CD4 cells?
Attachment entry Transcription Assembly of new virions Budding HIV receptors
What infections can you get when CD4 cells begin to get to moderately low levels?
Shingles Candida Oral hairy leucoplakia Molluscum contagiosum Kerion
What infections can you get with AIDS?
Pneumocystitis pneumonia
Infections, neoplasms, direct HIV effect, immunological
AIDS defining conditions
How does HIV present?
Generalised lymphadenopathy
Acute generalised rash
Glandular fever/flu-like illness
Prolonged episodes of HSV
Persistent frequently occurring candidiasis
Oral candida
Indicators of immune dysfunction
Recently developed or worsening skin conditions
Odd looking mouth lesions
Unexplained weight loss or night sweats
Persistent diarrhoea
Gradually increasing shortness of breath and dry cough
Recurrent bacterial infections - pneumococcal pneumonia
Recurrent/unexplained infections
How does acute HIV syndrome present?
Fever, sweats Sore throat Myalgia Rash Vomiting/diarrhoea Headache Lymphadenopathy Hepatosplenomagaly Mouth ulcers Myalgia/arthralgia Significant weight loss Lethargy and depression
How is HIV/AIDS diagnosed?
Venous blood sample - most accurate Salivary antibody screening Prick test Monitored via CD4 cell count HIV viral load
How is HIV/AIDS treated?
HAART
3+ antiretroviral drugs
Act on different points in HIV replication cycle to suppress virus
Significant impact on mortality and morbidity
Prevents HIV developing resistance to drugs
How common is breast cancer?
By far most common cancer in women
2nd most common cause of death in UK
Majority arise from either - epithelial lining of ducts (ductal) or from epithelium of terminal ducts of lobules (lobular)
Affects 1 in 9 women
Rare in men - 1%
Risk increases with age - less than 5% below 35
Most common histological subtype infiltrating ductal carcinoma 70%
Lobular carcinoma 10-15%
Medullary cancers 5% tend to affect younger patients
Colloid/mucoid cancers tend to affect the elderly
What does the UK breast cancer screening programme involve?
Biplanar digital mammography every 3 years in women aged 50-70 years and improvements in multi-modality treatment have increased overall survival and rates of cure
What is familial breast cancer?
5-10% breast cancers due to BRCA1 mutation (long arm chromosome 17) or BRCA2 (long arm chromosome 13)
BRCA1 higher risk
Tumour suppressor genes that act as inhibitors of cellular growth
BRAC1 65% risk
BRCA2 45%
Sronger incidence of BRCA1 than BRCA2
What can increase your risk of getting breast cancer?
Increasing age FHx in 1st degree relative BRCA1 or 2 mutation Never having borne a child/first child after 30 Not having breast fed Early menarche and late menopause Radiation to chest HRT with oestrogen and progesterone Combined OCP Obesity Past breast cancer
What are the possible symptoms of breast cancer?
Most women with symptomatic present with painless, increasing mass that may also be associated with
- Skin tethering
- Ulceration
- Nipple discharge
- In inflammatory cancer - oedema and erythema
What is a possible differential diagnosis of breast cancer?
Benign breast disease
- Fibroadenoma
- Breast cysts
- Intraductal papilloma
How is breast cancer diagnosed?
Clinical examination
Radiology - USS for < 35, mammography and USS > 35
Histology and cytology
- Fine needle aspiration - if cystic lump - clear fluid (discard and reassure), bloody fluid found (cytology)
USS guided biopsy
- If there is residual mass/solid lump - if malignant plan treatment
Ask direct questions eg past lumps, FHx, pain, changes in size related to menstrual cycle, skin changes, nipple discharge
Consider metastatic disease - weight loss, breathlessness, back pain, abdominal mass
Check oestrogen receptor, progesterone receptor and human epidermal growth factor 2 status as will affect treatment options
Expression of HER2 adverse factor for small, otherwise good prognosis tumours - tumour more likely to grow and divide
How is breast cancer staged?
CXR, MRI, CT, liver, USS, bone scan, LFTs, Ca2+
Stage 1 - confined to breast, mobile
Stage 2 - growth confined to breast, mobile, lymph nodes in ipsilateral axilla
Stage 3 - tumour fixed to muscle but not chest wall, ipsilateral lymph nodes matted and may be fixed, skin involvement larger than tumour
Stage 4 - complete fixation of tumour to chest wall, distant metastases
TMN
- T1 < 2cm
- T2 2-5cm
- T3 > 5cm
- T4 fixed to chest wall
- N1 mobile, ipsilateral nodes
- N2 fixed nodes
- M1 distant metastases
How is stage 1-2 breast cancer treated?
Surgery - removal of tumour by wide local exision or mastectomy, +/- breast reconstruction, axillary node sampling/surgical clearance
Radiotherapy - for those with invasive cancer, S/E pneumonitis, pericarditis, rib fracture
Chemotherapy - alongside surgery
Endocrine therapy - aim to reduce oestrogen activity used in ER and PR positive disease, only used post-menopausal
- Oestrogen receptor blocker eg oral tamsulosin
- Aromatase inhibitors that target peripheral oestrogen synthesis eg oral anastrozole
If premenopausal and ER positive ovarian ablation via surgery/radiotherapy to stop oestrogen synthesis, GnRH analogues
How is stage 3-4 breast cancer treated?
Radiotherapy to bony lesions - bisphosphonates
Oral tamoxifen used in ER positive - if relapse after initial success then consider chemotherapy
Oral trastuzumab for HER2 positive tumours
CNS surgery for solitary and easily accessible metastases if not radiotherapy
How can you prevent breast cancer?
Promote awareness
Screening - 2 view mammography every 3 years for women aged 47-73 years
What is amyloidosis?
Group of disorders of protein metabolism where there is extracellular deposition of insoluble fibrillar protein called amyloid which is resistant to degradation
Localised amyloidosis deposition occurs in brain of patients with Alzheimer’s
Local amyloid deposition also feature of T2DM and long-term haemodialysis
How common is amyloidosis?
Rare disease
Systemic amyloidosis is fatal and responsible for 1 in 1500 deaths per year in UK
Can be acquired or inherited
May be localised or systemic
How is amyloidosis classified?
By nature of precursor plasma proteins that form the fibrillar deposits
AL amyloid - primary
AA amylodosis - secondary
ATTR familial
What is primary amyloidosis?
AL amyloidosis
Abnormal plasma cells in bone marrow produce light chain amyloid protein
Light chains normally part of healthy immunoglobulins and thus proteins referred to as amyloidogenic monoclonal immunoglobulin fibrillar light chain proteins
Protein get deposited and result in organ failure and death
Associated with myeloma and non-Hodgkin’s lymphoma
How does AL amyloidosis present and how is it treated?
Affects normal structures and function of affected tissue
Kidneys - glomerular lesions resulting in proteinuria and nephrotic syndrome
Heart - restrictive cardiomyopathy, arrhythmias and angina
Nerves - peripheral and autonomic nephropathy and carpal tunnel syndrome
GI - macroglossia, malabsorption, weight loss, perforation, haemorrhage, obstruction, hepatomegaly
Vascular - purpura especially periorbital
Treatment - optimise nutrition, alkylating agent and corticosteroid eg oral melphalan and prednisolone
What is secondary amyloidosis?
AA amyloidosis
Derived from serum amyloid A, an acute phase protein, related to chronic inflammatory disorders and chronic infection
- RA, UC/Crohn’s, familial Mediterranean fever, chronic infections eg TB, bronchiectasis, osteomyelitis
How does AA amyloidosis present and how is it treated?
Affects kidneys, liver and spleen
Proteinuria, nephrotic syndrome, hepatosplenomegaly, macroglossia NOT SEEN, cardiac involvement rare
Treat underlying cause
What is ATTR familial amyloidosis?
Autosomal dominant condition
Usually caused by mutations in transthyretin where mutant protein forms amyloid fibils
How does ATTR familial amyloidosis present and how is it treated?
Sensory and autonomic neuropathy
Cardiomyopathy
Renal involvement
Treatment - liver transplant can cure
How is amyloidosis diagnosed?
Biopsy of affected tissue
- Rectum or subcutaneous fat relatively non-invasive sites for biopsy and positive 80%
- Biopsy positive if there is congo red staining with red-green birefringence under polarised light microscopy
What is the prognosis of amylosis?
Median survival 1-2 years
Patients with myeloma and amyloidosis have shorter survival then those with myeloma alone
What is lymphoedema?
Chronic, non-pitting oedema caused by lymphatic insufficiency ie failure of lymphatic drainage
Most commonly affects legs and tends to progress with age
Legs can become enormous and prevent normal shoes being worn
Chronic disease may cause secondary cobblestone thickening of skin
How is lymphoedema classified?
Primary lymphoedema
- Presents in early life
- Due to inherited deficiency of lymphatic vessels
Severe lymphoedema
- Due to obstruction of lymphatic vessels - filiarial infection, malignant disease, trauma, radiotherapy, surgery
How is lymphoedema treated?
Compression stockings
Physical massage
For filariasis infection give oral diethylcarbamazine
- Kills worms and microfilaeiae
- Serious allergic responses may occur as parasites are killed
- S/E facial swelling, headaches, lethargy
If recurrent cellulitis, long-term antibiotics advisable as each episode of cellulitis will further damage lymph vessels eg prophylaxis low-dose antibiotics twice daily
Surgery should be avoided
What are sarcomas?
Group of rare solid tumours of connective tissues - more than 50 different histological subtypes known
Cancers develop in muscle, bone, nerves, cartilage, tendons, blood vessels and fatty and fibrous tissues
Mesodernal origin tumours
What is the epidemiology of sarcoma?
1% of all adult tumours
Soft tissue sarcoma more common than bone sarcoma (80%)
When is soft tissue sarcoma more common?
Can affect any body part
More common in middle aged and elderly
Eg leiomyosarcoma
STS red flag - lump that is big/getting bigger, deep in body tissues, painful and occurs when older
How does STS present?
Lump that is painless at first
Pain and soreness as lump grows and presses against nerves and muscles
Leiomyosarcoma in womb may cause bleeding other than when patient having period/menopause
Most metastasis to lung initially
How are STS diagnosed
MRI and core needle biopsy
CT thorax for lung metastases
How are STS treated?
Surgical resection and chemotherapy +/- radiotherapy
Chemotherapy +/- radiotherapy is unresectable
How common are bone sarcomas?
Only affect less than 500 people in UK per year
More common under 20
Osteosarcoma
Red flags - non-mechanical bone pain, night pain, palpable bony mass, average duration of symptoms 3m, bone destruction, new bone formation, periosteal swelling, soft tissue swelling suggests new tumour
How does bone sarcoma present?
Non-mechanical bone pain still present when lying still Swelling Feeling tired Pyrexia Weight loss
How is sarcoma diagnosed?
X-ray
CT/MRI
Bone scans and biopsy
How is sarcoma treated?
Wide surgical resection and reconstruction
Chemotherapy +/- radiotherapy
What chemotherapy regimen may you use in breast cancer stages 1-2?
Epirubicin + CMF (cyclophosphamide, methotrexate, fluorouracil)
Name an oestrogen receptor blocker?
Tamoxifen
What are the side effects of tamoxifen?
Hot flushes Weight gain Mood changes Vaginal discharge Thromboembolism
Name an aromatase inhibitor
Anatrozole
How do aromatase inhibitors work?
Target peripheral oestrogen synthesis
What are the side effects of aromatase inhibitors?
Hot flushes Vaginal dryness Arthralgia Skin rash Osteoporosis
