Miscellaneous Flashcards
1
Q
What type of virus is HIV?
A
Retrovirus. These are enveloped viruses.
2
Q
In what should you especially consider HIV?
A
Think of testing for HIV infection when faced with recurrent shingles, candidiasis etc.
Multi-dermatomal shingles
Unexplained lymphadenopathy
Unexplained weight loss or diarrhoea, night sweats, PUO
Oral/oesophageal candidiasis or hairy leukoplakia
Flu-like illness, rash, meningitis
Unexplained blood dyscrasias.
3
Q
What HIV screening test is preferred?
A
Venous blood sample.
4
Q
What do 4th generation HIV tests detect?
A
p24 antigens and HIV antibodies.
They will detect the vast majority of infections at 4 weeks. If negative, repeat at 8 weeks if high suspicion.
5
Q
What are HIV point of care tests?
A
Finger prick blood. Lower sensitivity and specificity. Gives false positive and negative results.
6
Q
What is the natural history of HIV?
A
- Primary infection
- Acute HIV syndrome, wide dissemination of virus, seeding of lymphoid organs (acute rise in HIV RNA then fall and fall in CD4 count followed by a gradual rise)
- Clinical latency
- Constitutional symptoms (progressive generalised lymphadenoapthy)
- Opportunistic diseases (AIDS when CD4<200)
- Death.
7
Q
What happens to CD4+ T lymphocyte count from clinical latency to death?
A
Decreases.
8
Q
What happens to HIV RNA between clinical latency and death?
A
Increases. Increases rapidly from constitutional symptoms to death.
9
Q
When is high risk of transmission of HIV?
A
The first month or so post infection due to the high viraemia.
10
Q
After initial exposure of HIV, how long is the average period that somebody is asymptomatic for?
A
Seven years.
11
Q
How is RNA copied into DNA?
A
Reverse transcriptase.
12
Q
What group of viruses does HIV-1 and HIV-2 belong to?
A
Lentivirus.
13
Q
How many HIV subtypes are there?
A
9.
14
Q
How do viruses replicate?
A
- Attachment: viral and cell receptors e.g. HIV (gp120 and CD4)
- Cell entry: only central viral ‘core’ carrying the nucleic acid and some associated proteins enter the host cell
- Interaction with host cells: use cell materials (enzymes, amino acids, nucleotides) for their replication
- Replication: may localise in the nucleus, cytoplasm or both. Production of progeny viral nucleic acid and proteins
- Assembly: occurs in the nucleus (e.g. herpesviruses), in the cytoplasm (e.g. poliovirus) or at cell membrane (e.g. influenza virus)
- Release: by bursting open (lysis) of the cell or by ‘leaking’ (exocytosis) from the cell over a period of time e.g. HIV.
15
Q
What immune response do CD4 T cells act in?
A
Acquired immune response.
16
Q
What is the gold of CD4 T cells?
A
They are responsible for organising, recruiting and facilitating the maturation of B antibody producing cells and T CD8 killer cells.
17
Q
What types of T helper cells do CD4 T cells mature into?
A
On presentation of antigen CD4 cells mature into two types of t helper cell.
1. T helper cell 1 produces specific interleukins (IL 4, 5, 10,13 ) that cause maturation of B lymphocytes into plasma cells. The plasma cells then produce specific antibodies IgG etc against the specific antigen in question. This allows a more prolonged and effective antibody response.
2. T helper cell 2 produces IFN alpha and TNF. These cytokines activate further CD8 cells, turning them into Cytotoxic T lymphocytes (CTL) and NK cells. CTLs then produce an enzyme ( perforin ) that directly kill cells with antigen on /in.
Note IFN alpha is an important cytokine in the bodies defence against TB
CD8 Killer T cells Act as direct killer cells by killing any cell that is seen to be infected with the specific foreign agent.
18
Q
What does HIV result in?
A
The death of CD4+ T lymphocytes.
19
Q
What does HIV replicate within?
A
CD4 T cells.
20
Q
What is the structure of a virus?
A
Lipid envelope around outside
Protein capsid
Nucleic acid in centre
Virion associated polymerase in the centre.
21
Q
How does HIV replicate?
A
- HIV binds via gp120 envelope glycoprotein, to CD4 receptors on T helper cells, monocytes, macrophages and neural cells
- CD4+ cells migrate to lymphoid tissue, where virus replicates
- New viruses are released, and infect new CD4+ cells
- As infection progresses, depletion or impaired function of CD4+ cells and immunity
- After cell entry, viral reverse transcriptase makes DNA copy of RNA genome
- Viral integrase enzymes integrates this into host DNA
- Viral RNA is spliced, core viral proteins are synthesized, then cleaved by viral protease into enzymes and building blocks of the virus
- Completed viruses are then released by budding
- Number of circulating viruses (viral load) predicts progression to AIDS.
22
Q
What are the 9 steps of HIV replication?
A
- Attachment
- Entry
- Uncoating
- Reverse transcriptase (error prone so genetic variability)
- Genome integration
- Transcription of viral RNA
- Splicing of mRNA and translating into proteins
- Assembly of new virions
- Budding.
23
Q
What cells can become infected with HIV?
A
CD4 T cells.
Macrophages (have CD4 and CCR5).
Possibly dendritic cells infected early on.
Occasionally: astrocytes, renal epithelial cells.
24
Q
What causes AIDS?
A
Depletion of CD4 T cells.
25
How does HIV virus enter the body?
Via mucosa (vagina, rectum, intestinal, breastfeeding in infants).
26
What are the mechanisms of CD4 T lymphocyte depletion?
```
Direct cytotoxicity of directly infected cells
Activation induced death
Decreased production
Redistribution
Bystander cell killing.
```
27
What are the sanctuary sites for HIV infection?
Genital tract, central nervous system, gastrointestinal system and bone marrow.
28
What cells act as a reservoir for HIV?
Macrophages, microglia.
29
What favours HIV viral replication?
Excessive immune activation.
30
What did HIV-1 evolve from?
Simian immunodeficiency virus in chimpanzees.
31
What are infectious examples of AIDs defining conditions?
```
Candidiasis: oesophageal/lung
Extra-pulmonary Cryptococcosis
Cryptosporidiosis >1 month
CMV: any organ except liver, spleen, lymph nodes
Mycobacterium TB
Toxoplasmosis of internal organs
HSV with muco-cutaneous ulcer >1 month
Pneumocystis jiroveci (carinii) pneumonia (PCP)
Recurrent bacterial pneumonia.
```
32
What neoplasms are examples of AIDs defining conditions?
Invasive cervical carcinoma
Kaposi’s carcinoma
Primary CNS Lymphoma
Non-Hodgkin’s lymphoma.
33
What CD4 T cell count constitutes AIDs defining conditions?
<200.
34
What are some of the direct HIV effect AIDs defining conditions?
HIV dementia/encephalopathy
| HIV associated wasting.
35
What is HIV seroconversion?
The period during which the body starts producing detectable levels of HIV antibodies.
36
What is the only symptom in HIV clinical latent phase?
Persistent generalised lymphadenopathy.
| Enlarged lymph nodes involving at least 2 non-contiguous sites other than inguinal nodes.
37
How often should HIV +ve women have a cervical smear?
Annually.
38
What are the 3 respiratory diseases in HIV?
1. Bacterial (often pneumococcal) pneumonia
2. Tuberculosis
3. Pneumocystis jiroveci pneumonia (PCP).
39
At what CD4 count does cerebral toxoplasmosis occur?
<100.
40
What are the CNS mass lesions in HIV?
Cerebral Toxoplasmosis
Primary CNS Lymphoma
Tuberculoma.
41
What are the ophthalmic lesions in HIV?
CMV
Toxoplasmosis
Choroidal Tuberculosis.
42
What are the types of meningitis in HIV?
Cryptococcal
Tuberculous
Pneumococcal.
43
What are the 3 HIV related neoplasms?
1. Lymphoma (CD4 <100, systemic Non-Hodgkin's lymphoma)
2. Cervical neoplasia
3. Kaposi’s sarcoma.
44
What are the 2 aims of HAART?
1. Reduce viral load to <50 copies
| 2. Increase CD4 count.
45
Why does circumcision reduce the risk of HIV?
* By removing foreskin, circumcision reduces the ability of HIV to penetrate due to keratinization of the inner aspect of the remaining foreskin.
* The inner part of the foreskin contains many Langherhans cells, that are prime targets for HIV. Some of these are removed with the foreskin.
* Ulcers, characteristic of some STI’s that can facilitate HIV transmission, often occur on the foreskin. By removing the foreskin, the likelihood of acquiring these infections is reduced.
* The foreskin may suffer abrasions or inflammation during sex that could facilitate the passage of HIV.
46
What are the 3 drugs in HAART?
2 nucleoside reverse-transcriptase inhibitors (NRTIs) e.g. zidovudine, didanosine and lamivudine + 1 non-nucleoside reverse-transcriptase inhibitor (NNRTI).
Or 2 NRTIs + 1 Protease inhibitor (PI).
47
What are the 3 must haves for consent?
1. Voluntary: free from pressure and incentives
2. Informed: risk and benefits and alternatives
3. Made by someone with capacity.
48
What are the 4 things someone must have to have capacity?
1. Understand
2. Retain
3. Weigh
4. Communicate their decision.
49
When was the Mental Capacity Act written?
2005.
50
What does the Mental Capacity Act state?
A person must be presumed to have capacity unless it is established that he lacks capacity.
An act done, or a decision made, under this Act for or on behalf of a person who lacks capacity, must be done, or made in his best interests.
51
What are causes of reduced capacity?
Learning disability, dementia, mental illness and impaired consciousness.
52
What happens if somebody does not have capacity?
Lasting power of attorney or advance directive.
If there is no lasting power of attorney or advance directive, a healthcare professional can act in the patient's best interest. The patient should always be involved in this as much as possible.
53
What is the only exception for an adult giving consent on behalf of another adult?
Lasting power of attorney.
54
Who should be appointed if there is no family or friend to advise and support the patient?
An independent mental capacity advocate.
55
What does the Mental Capacity Act require consideration of?
1. Whether the patient could have capacity and when that might occur
2. The patient's past and present wishes and feelings
3. Patient's beliefs and values that would be likely to influence any decision
4. Other factors he might consider to decide
5. Consultation about 2-4 with anyone named as needing to be consulted e.g. carers, persons interested in his welfare, donees of a lasting power of attorney.
56
What do you do in an emergency situation if there is doubt?
Give treatment.
57
What is Gillick competence?
Providing treatment to under 16s without parental consent if they are deemed competent.
58
Can parents refuse treatment for children if it is in their best interests?
No.
59
Can a young person refuse treatment if competent?
Yes.
60
What are types of benign breast disease?
Fibroadenoma.
Breast cysts.
Duct ectasia.
Intraductal papilloma (benign tumours within breast ducts).
61
What are the risk factors for breast cancer?
Never giving birth, 1st pregnancy >30 years old, early menarche, late menopause, HRT, obesity, BRCA genes, not breastfeeding, past breast cancer.
62
What are BRCA1 and BRCA2?
Tumour suppressor genes.
63
What is premalignant for breast cancer?
Non-invasive ductal carcinoma-in-situ. Seen as microcalcification on mammography.
64
What are the types of breast cancer?
Invasive ductal carcinoma: 70%.
Invasive lobular carcinoma: 10-15%.
Medullary cancers: 5%, affecting younger patients.
65
What percentage of breast cancers are oestrogen receptor +ve (better prognosis)?
60-70%.
66
What percentage of breast cancers over-express HER2 (growth factor receptor gene, aggressive disease, poorer prognosis)?
30%.
67
What is the triple assessment for all breast lumps?
1. Clinical examination
2. Histology/cytology: fine needle aspiration or core biopsy
3. Mammography/ultrasound.
68
What is the staging of breast cancer?
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/fixed, skin involvement larger than tumour.
Stage 4: complete fixation of tumour to chest wall, distant metastases.
Also TNM staging.
69
What are the treatments for breast cancer?
Surgery: wide local excision (WLE) or mastectomy ± breast reconstruction + axillary node sample/surgical clearance/sentinel node biopsy.
Radiotherapy: after WLE. SE are pneumonitis, pericarditis, rib fractures.
Chemotherapy: adjuvant chemotherapy improves survival and reduces recurrence. Epirubicin + CMF (cyclophosphamide + methotrexate + 5-FU).
Endocrine agents: aim to decrease oestrogen activity, used in oestrogen receptor (ER)/progesterone receptor (PR) +ve disease. Tamoxifen is an oral ER blocker. Anastrozole is an aromatase inhibitor. Both used only if post-menopausal. Pre-menopausal and ER+ve indicates ovarian ablation (surgical/radiotherapy) or GnRH analogues e.g. goserelin.
70
What drug do you give for HER2 +ve tumours?
Trastuzumab with chemotherapy.
71
What drug do you give for ER +ve tumours?
Tamoxifen.
72
What is the requirement for a paracetamol overdose?
150mg/kg or 12g in adults may be fatal.
73
What are the later stages of paracetamol overdose?
Jaundice and ecephalopathy from liver damage +/- AKI.
74
What is the antidote for a paracetamol overdose?
N-acetylcysteine (IV infusion).
75
What should be given if somebody presents within 4 hours with a paracetamol overdose?
Activated charcoal as it is a GI decontaminant so reduces the absorption of many drugs from the gut.
76
What does ER breast cancer mean?
Grows as a result of oestrogen.
77
What is HER2 breast cancer?
Progesterone receptor.
78
What is amyloidosis?
Group of disorders characterized by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation.
Also features in Alzheimer’s disease, type 2 DM, and haemodialysis-related amyloidosis.
79
What are the 2 types of amyloidosis?
Systemic: protein deposits in multiple organ systems e.g. AL amyloidosis and AA amyloidosis.
Localised: protein deposits in one organ.
80
What are the symptoms of amyloidosis in the kidneys?
Amyloid deposits can damage podocytes which can cause albumin to leak into the urine which causes proteinuria. Also causes hypoalbuminaemia which lowers oncotic pressure and causes oedema. This also causes nephrotic syndrome (proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia.
Swelling in face, ankles and legs.
81
What are the symptoms of amyloidosis in the heart?
Amyloid deposits stiffen heart walls which causes restrictive cardiomyopathy and then congestive heart failure.
Also interfere with electrical conduction which causes arrhythmias.
Palpitations and SOB.
82
What are the symptoms of amyloidosis in the intestines?
Amyloid deposits damage intestinal villi and so less nutrient absorption.
Enlarge liver, spleen and tongue too.
Malabsorption and weight loss.
83
What are the symptoms of amyloidosis in the nervous system?
Amyloid deposits can damage peripheral nerves (carrying sensory and motor fibres) and autonomic nerves (controlling digestion and BP).
Numbness/pain in fingers and toes, diarrhoea and constipation, orthostatic hypotension.
CNS: usually spared except in Alzheimer’s (memory loss and difficulty learning new skills).
84
What are the symptoms of amyloidosis in the brain?
Alzheimer’s Disease: A-beta-peptides collect in brain which cause plaques that sit on the outside of neurons and interfere with neuron-neuron signalling.
Amyloid plaques also deposit in vessel walls in brain called amyloid angiopathy which weaken walls and increase risk of haemorrhage.
Inflammation causes damage and so decreased brain function e.g. memory.
85
What is a symptom of amyloidosis?
Large tongue: interfere with speech, swallowing and cause noisy breathing at night.
86
What are the investigations for amyloidosis?
Biopsy or involved organism:
• Congo red stain and if amyloid, goes pink
• Polarised light and if amyloid, goes apple green.
87
What is the management of amyloidosis?
No way to remove deposits.
| Extensive organ damage requires transplantation.
88
What is AL amyloidosis?
Primary amyloidosis.
| Immunoglobulin light chain protein which is misfolded and deposited.
89
What are the causes of AL amyloidosis?
* Myleoma
* Waldenstroms
* Lymphoma.
90
What is AA amyloidosis?
Secondary amyloidosis.
Chronic infections e.g. TB.
Inflammation e.g. Rheumatoid Arthritis.
Malignancy: Non-Hodgkin’s lymphoma.
91
What is the pathophysiology of AA amyloidosis?
When there is a lot of inflammation e.g. in rheumatoid arthritis, UC/Crohn’s and chronic infections e.g. TB, bronchiectasis and osteomyelitis, and it goes on for a very long time, there is a lot of serum amyloid A in the blood which spontaneously misfolds into amino acid amyloidosis which builds up in the tissues and causes amyloidosis.
92
What is AA amyloidosis derived from?
Serum amyloid A which is an acute phase protein, released from the liver when there is inflammation.
93
What does AA amyloidosis affect?
Kidney, liver and spleen.
94
What are the symptoms of AA amyloidosis?
May present with proteinuria, nephrotic syndrome or hepatosplenomegaly.
Macroglossia is not seen.
95
What is familial amyloidosis?
Autosomal dominant. Mutations in transthyretin, a transport protein produced by the liver. Causes a sensory or autonomic neuropathy +/- renal or cardiac involvement. Liver biopsy is curative.
96
Where does lymphoedema most commonly affect?
Legs, progresses with age.
97
What are the types of lymphoedema?
May be primary e.g. Milroy disease (autosomal dominant, lower leg swelling from birth, compression stockings, encourage exercise).
Or secondary due to obstruction of lymphatic vessels e.g. filarial infection (transmitted by 5 genera of mosquito, fever, lymphadenopathy, chyluria, elephantiasis and massive hydroceles), malignant disease, post-irradiation therapy.
98
What is sarcoma>
Cancer arising from cells of mesenchymal origin (fat, muscle etc).
Malignant tumours of cancellous bone, cartilage, fat, muscle, vascular or haematopoietic tissue.
99
When is sarcoma considered malignant?
* >5cm
* Increasing in size
* Deep to the deep fascia
* Painful.
100
What is the investigations for sarcoma?
MRI followed by needle biopsy.
101
What is the management of sarcoma?
Excision with wide margins then radiotherapy.
102
What are the symptoms of carbon monoxide poisoning?
Skin is pink (or pale) and not blue despite hypoxaemia. This is because carboxyhaemoglobin (COHb) displaces O2 from Hb binding sites. SpO2 from pulse oximeter may appear normal due to the same reason.
* Headache
* Vomiting
* High pulse
* Tachpnoea
* Severe: fits, coma, cardiac arrest.
103
What are the investigations of carbon monoxide poisoning?
ABG.
104
What is the management of carbon monoxide poisoning?
Remove source.
| Give 100% oxygen and levels should quickly return to normal.
105
What are the symptoms of organophosphate insecticides poisoning?
```
They inactivate cholinesterase, resulting increase in acetylcholine causes SLUD respons:
S alivation
L acrimation
U rination
D iarrhoea.
```
```
Also look for:
• Sweating
• Small pupils
• Muscle fasciculation
• Coma
• Respiratory distress
• Bradycardia.
```
106
What is the management for organophosphate insecticides poisoning?
* Wear gloves, remove soiled clothes and wash skin
* IV atropine
* IV pralidoxime.
107
What is salicylate poisoning?
Aspirin is a weak acid with poor water solubility. Uncoupling of oxidative phosphorylation leads to anaerobic metabolism which causes production of lactate and heat.
108
What are the symptoms of salicylate poisoning?
* Vomiting, dehydration, hyperventialation, tinnitus, vertigo, sweating
* Rarely: decreased GCS, seizures, hypotension and heart block, pulmonary oedema, hyperthermia
* Present with respiratory alkalosis, then develop metabolic acidosis.
109
What is the treatment for salicylate poisoning?
* Activated charcoal if present in <1h
* Correct alkalosis: IV sodium bicarbonate
* Dialysis may be needed.
110
What causes typhoid?
Caused by Salmonella typhi and Salmonella paratyphi.
111
How is typhoid spread?
Spread is faecal-oral.
112
What are the symptoms of typhoid?
* Malaise
* Headache
* High fever with bradycardia
* Cough
* Constipation and then diarrhoea after 1st week
* Rose spots on trunk.
113
What is the investigation for typhoid?
Isolation of Salmonella typhi from the blood (blood culture).
114
What is the management for typhoid?
* Fluid replacement and good nutrition
| * + ciprofloxacin oral.
115
What is poliomyelitis?
Highly contagious picornavirus.
116
How is poliomyelitis spread?
Spread by droplet or faecal-oral.
117
What are the symptoms of poliomyelitis?
* Flu prodome
* Pre-paralytic stage: fever, tachycardia, headache, vomiting, neck stiffness
* Paralytic stage.
118
What is the management for poliomyelitis?
No drugs work.
119
What innervates the breast?
Anterior and lateral cutaneous branches of 4th – 6th intercostal nerves.
120
What does the breast contain?
Mammory glands (modified sweat glands, consists of ducts and secretory lobules).
121
Where do breast veins drain into?
Axillary and internal thoracic veins.
122
Where is drainage of the breast?
* Axillary nodes: 75% drains here
* Parasternal nodes : (20%) drains here
* Posterior intercostal nodes: 5% drains here.
123
What breast tissue makes milk?
Glandular tissue.
124
Which cells secrete milk?
Alveolar cells.
125
Why is there cyclical breast pain with menstruation?
During menstruation, raised oestrogen and progesterone causes growth of alveolar cells.
After menstruation, hormone levels falls and so apoptosis. This can cause cyclical breast pain. Symptoms start within 2 weeks and improve at onset of menstrual period.
