Misc Flashcards
Acute mountain sickness
generally a self-limiting condition. Features of AMS start to occur above 2,500 - 3,000m, developing gradually over 6-12 hours and potentially last a number of days:
* Headache * Nausea
* Fatigue
Prevention and treatment of AMS
The risk of AMS may actually be positively correlated to physical fitness
* Gain altitude at no more than 500 m per day
* Acetazolamide (a carbonic anhydrase inhibitor) is widely used to prevent AMS and has a
supporting evidence base
* Treatment: descent
high altitude pulmonary edema (HAPE)
Descent
* Dexamethasone, nifedipine, phosphodiesterase type V inhibitors (Sildenafil)
* Oxygen if available
Hereditary Angioedema Description of disease
autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH) protein. C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in edema of tissues
Hereditary Angioedemam investigation
- C1-INH level is low
- Low C2 and C4 levels are seen, even between attacks
Hereditary Angioedemama Symptoms
Symptoms
* Attacks may be proceeded by painful macular rash
* Painless, non-pruritic swelling of subcutaneous/submucosal tissues
* May affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral edema)
* Urticaria is not usually a feature
Hereditary Angioedemama management
Acute: IV C1-inhibitor concentrate or FFP
* Anabolic steroid; Danazol may help
Galactosemia
a rare autosomal recessive condition caused by the absence of galactose-1- phosphate uridyl transferase. This results in intracellular accumulation of galactose-1-phosphate
Features
* Jaundice
* Failure to thrive
* Hepatomegaly
* Cataracts
* Hypoglycemia after exposure to galactose
* Fanconi syndrome
Diagnosis
* Urine reducing substances
DVT Risk Factors:
Hematological
* Thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency
* Polycythemia
* Paroxysmal nocturnal hemoglobinuria
* Hyperviscosity syndrome
Autoimmune
* Antiphospholipid syndrome * Behcet’s
Drugs
* Combined oral contraceptive pill: 3rd generation more than 2nd generation
* Antipsychotics (especially olanzapine) have recently been shown to be a risk factor
Other conditions
* Homocystinuria
Motion sickness
describes the nausea and vomiting which occurs when an apparent discrepancy exists between visually perceived movement and the vestibular systems sense of movement.
Management
* The BNF recommends hyoscine (e.g. Transdermal patch) as being the most effective treatment. Use is limited due to side-effects
* Non-sedating antihistamines such as cyclizine or cinnarizine are recommended in preference to sedating preparation such as promethazine
Acute intermittent porphyria (AIP) (Acute)
- Autosomal dominant
- Defect in porphobilinogen deAminase
- Results accumulation of delta aminolaevulinic acid and porphobilinogen
- ♀s, 20-40 year olds more likely to be affected (♀5:1)
- Typically present with abdominal symptoms, neuropsychiatric symptoms
- Hypertension and tachycardia common
- Urine turns deep red on standing
Acute intermittent porphyria (AIP) (Acute) Features
Abdominal: abdominal pain, vomiting
* Neurological: motor neuropathy
* Psychiatric: e.g. Depression
* Hypertension and tachycardia common
* No feces porphyria (can not be detected in
stool)
Acute intermittent porphyria (AIP) Diagnosis
Classically urine turns deep red on standing
* Raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
* Assay of red cells for porphobilinogen deaminase
* Raised serum levels of delta aminolaevulinic acid and porphobilinogen
Acute intermittent porphyria (AIP) treatment
Hematin: needs to be given very early in an attack to be effective. Effectiveness varies among individuals. They are not curative drugs, but can shorten attacks and reduce the intensity of an attack
Porphyria cutanea tarda (PCT) (Non-acute)
- Most common hepatic porphyria
- 80% sporadic and 20% autosomal dominant
- No neurological consequences only urine porphyria
- The exact frequency is not clear because many people with PCT never experience symptoms
- Defect in uroporphyrinogen decarboxylase
- May be caused by hepatocyte damage e.g. Alcohol, estrogens
- Classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands
- Urine: elevated uroporphyrinogen and pink fluorescence of urine under wood’s lamp
- Manage with chloroquine
Variegate porphyria
Autosomal dominant
* Defect in protoporphyrinogen oxidase
* Photosensitive blistering rash
* Abdominal and neurological symptoms
* More common in south africans
Kartagener’s syndrome
(also known as primary ciliary dyskinesia) was first described in 1933 and most frequently occurs in examinations due to its association with dextrocardia (e.g. ‘quiet heart sounds’, ‘small volume complexes in lateral leads’)
Features
* Dextrocardia or complete situs inversus
* Bronchiectasis
* Recurrent sinusitis
* Subfertility (secondary to diminished sperm motility and defective ciliary action in the fallopian
tubes)
Superior Vena Caval Obstruction (SVCO)
is an uncommon manifestation of mediastinal masses, but it is particularly for small-cell lung cancer.
Treatment depends on the cause and pace of the progression of symptoms.
* Although SVCO is an emergency in the presence of airway compromise, where possible it is
important to get tissue for a histological diagnosis, as some tumours are better treated with chemotherapy than radiotherapy. In this case, if feasible, a bronchoscopy would probably provide tissue for a diagnosis.
* For most tumours, radiotherapy is a good treatment and relieves symptoms in 90% of patients within 2 weeks.
* Patients should be sat up and given oxygen to provide initial relief.
* In severe cases high-dose steroids can be helpful.
* For patients with recurrent SVCO, insertion of expandable wire stents under radiological
guidance provides relief in a high proportion of patients.
Amyloidosis: diagnosis
iagnosis:
* Biopsy of abdominal wall fat, the rectum or a salivary gland can be examined for evidence of
characteristic amyloid deposits. The tissue is treated with Congo red stain, which combined
with polarized light makes the amyloid proteins appear apple-green on microscopy.
* Abdominal wall fat biopsy is not completely sensitive, and sometimes biopsy of an involved
organ (such as the kidney) is required to achieve a diagnosis
* The nature of the amyloid protein (type) can be determined by various ways:
o Protein electrophoresis or light chain determination
o Binding of particular antibodies to the amyloid found in the tissue
o Extraction of the protein and identification of its individual amino acids
AL amyloid
o L for immunoglobulin Light chain fragment
o Due to myeloma, Waldenstrom’s, MGUS
o Features include: cardiac and neurological involvement, macroglossia, periorbital
eccymoses
- AA amyloid
A for precursor serum amyloid A protein, an acute phase reactant o Seen in chronic infection/inflammation
o E.g. TB, bronchiectasis, rheumatoid arthritis
o Features: renal involvement most common feature
- β-2 microglobulin amyloidosis
Precursor protein is β-2 microglobulin, part of the major histocompatibility complex o Associated with patients on renal dialysis
Cardiac amyloidosis
Cardiac amyloidosis most commonly presents as restrictive cardiomyopathy, associated with AL Amyloidosis
Presentation:
* Typical presentation of right heart failure: o Jugular venous distension
o Peripheral oedema
o Orthopnoea and paroxysmal nocturnal dyspnea are typically absent
POEMS Syndrome
Polyneuropathy, Organomegaly, Endocrinopathy or Edema, M-protein and Skin abnormalities
plasma-cell proliferative disorder (typically myeloma), polyneuropathy and organomegaly. Average age of onset is 50 years, ♂:♀ 2:1. Its 5 years survival is 60% if untreated
Management:
* No treatment was found, just correct the hematological abnormality
* Conventional treatments for demyelinating neuropathy (Steroids, IV immunoglobulin and
plasma exchange) are ineffective; treatment must be aimed at the hematological disorder.
Systemic Mastocytosis
Results from a neoplastic proliferation of mast cells
Features
* Urticaria pigmentosa - produces a wheal on rubbing (Darier’s sign)
* Flushing
* Abdominal pain
* Monocytosis on the blood film
Diagnosis
* Raised serum tryptase levels
* Urinary histamine
CA 125
Ovarian cancer
CA 19-9
Pancreatic cancer
CA 15-3
Breast cancer
Thymomas associated with
are the most common tumor of the anterior mediastinum
Associated with
* Myasthenia gravis (30-40% of patients with thymoma)
* Red Cell Aplasia
* Dermatomyositis
* Also : SLE, SIADH
Testicular choriocarcinomas:
Diagnosis:
* Primary tumour can be very small and go undetected on testicular examination.
* Marked ↑ in β-HCG in the presence of a normal AFP and CEA.
* Scrotal ultrasound is used to support the diagnosis
* CTs are of significant value for staging.
Otitis externa Causes
- Infection: bacterial (Staphylococcus aureus, Pseudomonas aeruginosa) or fungal
- Seborrhoeic dermatitis
- Contact dermatitis (allergic and irritant)
Otitis externa features
Ear pain, itch, discharge
* Otoscopy: red, swollen, or eczematous canal
Initial management of otitis externa
Topical antibiotic or a combined topical antibiotic with steroid
- If the tympanic membrane is perforated aminoglycosides should not be used
- If there is canal debris then consider removal
- If the canal is extensively swollen then an ear wick is sometimes inserted
Malignant otitis externa
more common in elderly diabetics.
In this condition there is extension of infection into the bony ear canal and the soft tissues deep to the bony canal.
Intravenous antibiotics may be required.
Meniere’s disease Features
Recurrent episodes of vertigo, tinnitus and hearing loss (sensorineural). Vertigo is usually the prominent symptom
* A sensation of aural fullness or pressure is now recognised as being common
* Other features include nystagmus and a positive Romberg test (patient can’t stand-alone when
eyes closed and feet together)
* Episodes last minutes to hours
Meniere’s disease Management
ENT assessment is required to confirm the diagnosis
- Patients should inform the DVLA. The current advice is to cease driving until satisfactory control of symptoms is achieved
- Acute attacks: buccal or intramuscular prochlorperazine. Admission is sometimes required
- Prevention: betahistine may be of benefit
Tinnitus:
Meniere’s Disease
Otosclerosis
Acoustic neuroma
Hearing loss
Drugs - Aspirin Aminoglycosides Loop diuretics Quinine
Ramsay Hunt syndrome:
(herpes zoster oticus) is caused by the reactivation of the varicella zoster virus in the geniculate ganglion of the seventh cranial nerve.
Features
* Auricular pain is often the first feature
* Facial nerve palsy
* Vesicular rash around the ear
* Other features include vertigo and tinnitus
Hyperhidrosis:
describes the excessive production of sweat
Management options include
* Topical aluminium chloride preparations are first-line. Main side effect is skin irritation
* Iontophoresis: particularly useful for patients with palmar, plantar and axillary hyperhidrosis
* Botulinum toxin: currently licensed for axillary symptoms
* Surgery: e.g. endoscopic transthoracic sympathectomy. Patients should be made aware of the
risk of compensatory sweating
Benign paroxysmal positional vertigo (BPPV)
Features
* Vertigo triggered by change in head position (e.g. Rolling over in bed or gazing upwards)
* May be associated with nausea
* Each episode typically lasts 10-20 seconds
* Positive halpike manoeuvre
Indications for plasma exchange
ANCA positive vasculitis e.g. Wegener’s, Churg-Strauss
* Cryoglobulinemia
* Goodpasture’s syndrome
* Guillain-Barre syndrome
* Hyperviscosity syndrome e.g. Secondary to myeloma
* Myasthenia gravis
* TTP/HUS
Macroglossia causes
Causes
* Hypothyroidism
* Acromegaly
* Amyloidosis
* Duchenne muscular dystrophy
* Mucopolysaccharidosis (e.g. Hurler syndrome)
Alpha-1 Antitrypsin (A1AT) deficiency Genetics
Common inherited condition caused by a lack of a protease inhibitor (Pi) normally produced by the liver
Located on chromosome 14
* A1AT deficiency is inherited in an autosomal recessive /co-dominant fashion
* Alleles classified by their electrophoretic mobility - M: normal, S: slow, and Z: very slow
* Normal = PiMM
* Homozygous PiSS (50% normal A1A T levels)
* Homozygous PiZZ (10% normal A1A T levels)
Alpha-1 Antitrypsin (A1AT) Features
Features
* Patients who manifest disease usually have PiZZ genotype
* Lungs: panacinar emphysema, most marked in lower lobes
* Liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children
Alpha-1 Antitrypsin (A1AT) investigations and Management
Investigations
* A1AT concentrations
Management
* No smoking
* Supportive: bronchodilators, physiotherapy
* Intravenous α1-antitrypsin protein concentrates
* Surgery: volume reduction surgery, lung transplantation
Reye’s syndrome - features include:
severe, progressive encephalopathy affecting children that is accompanied by fatty infiltration of the liver, kidneys and pancreas.
features include:
* May be history of preceding viral illness
* Encephalopathy: confusion, seizures, cerebral oedema, coma
* Fatty infiltration of the liver, kidneys and pancreas
* Hypoglycaemia
Clubbing
Cardiac causes
* Cyanotic congenital heart disease (Fallot’s, TGA)
* Bacterial endocarditis
* Atrial myxoma
Respiratory causes
* Lung cancer
* Pyogenic conditions: cystic fibrosis,
bronchiectasis, abscess, empyema
* Asbestosis, mesothelioma
* Fibrosing alveolitis
Other causes
* Crohn’s, to a lesser extent UC
* Cirrhosis, primary biliary cirrhosis
* Graves’ disease (thyroid acropachy)
* Rare: Whipple’s disease
Syncope - Reflex syncope
Vasovagal: triggeres; emotion, pain, stress or orthostatic factors. Often referred to as ‘fainting’
* Situational: cough, micturition, gastrointestinal
* Carotid sinus syncope
Carotid sinus hypersensitivity (CSH)
diagnosis is only made after ischemic heart disease or rhythm disturbance have been excluded.
CSH may be predominantly cardioinhibitory (bradycardia), vasodilatory (hypotension), or a mixture of the two.
Cardioinhibitory is usually managed with insertion of a dual-chamber pacemaker, and vasodilator is managed with support stockings, fludrocortisone and midodrine.
Orthostatic syncope
- Primary autonomic failure: Parkinson’s disease, Lewy body dementia
- Secondary autonomic failure: e.g. Diabetic neuropathy, amyloidosis, uraemia
- Drug-induced: diuretics, alcohol, vasodilators
- Volume depletion: hemorrhage, diarrhoea
Cardiac syncope
- Arrhythmias: bradycardias (sinus node dysfunction, AV conduction disorders) or tachycardias (supraventricular, ventricular)
- Structural: valvular, myocardial infarction, hypertrophic obstructive cardimyopathy
- Others: pulmonary embolism
Fibromyalgia
Syndrome characterized by widespread pain throughout the body with tender points at specific anatomical sites. The cause of fibromyalgia is unknown.
Features
* Pain: at multiple site, sometimes ‘pain all over’
* Lethargy
* Sleep disturbance, headaches, dizziness are common
Monoclonal Antibodies
This involves the fusion of myeloma cells with spleen cells from a mouse (recent advances: rabbit B-cells) that has been immunized with the desired antigen.
The resulting fused cells are termed a hybridoma and act as a ‘factory’ for producing monoclonal antibodies.
The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies (HAMAs).
This problem is overcome by combining the variable region from the mouse antibody with the constant region from a human antibody.
Rituximab
Anti-CD20
non-Hodgkin’s lymphoma
Infliximab
anti-TNF
rheumatoid arthritis and Crohn’s
Cetuximab
anti epidermal growth factor receptor
metastatic colorectal cancer and head and neck cancer
Trastuzumab
anti-HER2, anti EGF receptor
metastatic breast cancer
Alemtuzumab
anti-CD52
Types of Transplants:
Autograft: when the same individual acts as donor and recipient
* Isograft: when donor and recipient are genetically identical
* Allograft: when donor and recipient are genetically dissimilar but belong to same specimen
* Xenograft: when donor and recipient belong to different specimen
* Orthotopic transplant: when the transplanted part is placed in its normal anatomical location
* Heterotropic transplant: when the transplanted part is placed in different anatomical location
Post Cranial Irradiation Somnolence Syndrome
Features
Excessive somnolence
* Lethargy and clumsiness
* Tends to occur around 11-21 or 31-35 days after high dose cranial radiotherapy.
* No focal cause is identified and it is postulated that the condition may occur due to post
irradiation demyelination.
* No specific therapy is required, some case reports suggest that corticosteroids may be of use but
the evidence is not firmly established.
Acute myeloid leukemia genes
5: deletion 7: deletion
Auto Dom Polycystic Kidney Disease genes
Type-I: 16 Type-II: 4
α-1 antitrypsin (A1AT) deficiency
gene 14 - lack of a protease inhibitor (Pi)
α-thalassemia gene
16 - deficiency of α chains in hemoglobin
Alzheimer’s disease
21: amyloid precursor protein 14: presenilin-I 1: presenilin -II
Autoimmune polyendocrinopathy syndrome
21
Cystic fibrosis (CF)
chromosome 7 - autosomal recessive
Cystinuria
2: SLC3A1 gene, 19: SLC7A9
autosomal recessive
familial adenomatous polyposis
5 - autosomal dominant
Familial Motor neuron disease
chromosome 21 - superoxide dismutase deficiency
Friedreich’s ataxia
chromosome 9 - autosomal recessive, trinucleotide repeat disorder
Hemochromatosis
chromosome 6 - autosomal recessive
HLA antigens
chromsome 6
Marfan’s syndrome
chromosome 15 - autosomal dominant
Myotonic dystrophy
autosomal dominant trinucleotide repeat disorder
NF1
chromosome 17 neurofibromatosis has 17 characters
Noonan’s Syndrome
autosomal dominant
chromosome 12
p53 gene
17p tumour suppressor gene
Von Hippel-Lindau
chromosome 3
autosomal dominant
Burkitt’s lymphoma genes
t(8;14) translocation
Chronic myeloid leukemia genes
t(9:22)
BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
Philadelphia chromosome95%
Mantle cell lymphoma
t(11;14)
deregulation of the cyclin D1 (BCL-1) gene
promyelocytic leukemia (M3)
t(15;17)
fusion of PML and RAR-α genes
- Drug induced pneumonitis →
methotrexate or amiodarone.
Bullae on hands and fragule SKIN torn by minor trauma
porphyria cutanea tarda.
Primary hrperparathyroidism →
high Ca, normal/low PO4, normal/high PTH (in
Middle aged man with KNEE arthritis →
gonococcal sepsis (older people → Staph).
.Sarcoidosis, erythema nodosum, arthropathy →
Loffgrens syndrome benign, no Rx
needed.
TREMOR postural, slow progression,titubation, relieved by OH→
benign essential
.Contraindications lung Surgery →
FEV dec bp 130/90, Ace inhibitors (if proteinuria
analgesic induced headache.
Temporal tenderness→
temporal arteritis → steroids > 90% ischemic neuropathy, 10%
retinal art occlusion.
Severe retroorbital, daily headache, lacrimation →
cluster
. Diagnosis of polyuria →
water deprivation test, then DDAVP.
. Insulinoma →
24 hr supervised fasting hypoglycemia.
Diarrhea, bronchospasm, flushing, tricuspid stenosis →
gut carcinoid c liver mets.
Hepatitis B with general deterioration →
hepaocellular carcinoma.
Albumin normal, total protein high →
myeloma (hypercalcemia, electrophoresis).
HBsAg positive, HB DNA not detectable →
chornic carier.
. Inf MI, artery invlived →
Right coronary artert.
Aut dom conditions
Achondroplasia, Ehler Danlos, FAP, FAMILIAL hyperchol,Gilberts, Huntington’s, Marfans’s, NFT I/II, Most porphyrias, tuberous sclerosis, vWD, PeutzJeghers.
X linked:
Beck/Duch musc dyst, alports, Fragile X, G6PD, Hemophilia A/B.
Aortic Stenosis
s2 paradoxical split, length proportional to severity
Mitral stenosis:
loud S1 (soft s1 if severe), opening snap.. Immobile valve → no snap.
.Restrictive Cardiomyopathy
sclerodermma, amyloid, sarcoid, HCT, glycogen storage,
Gauchers, fibrosis, hypereosinophilia Lofflers, caracinoid, malignancy, radiotherapy,
Horners – sweating lost in upper face only –
lesion proximal to common carotid artery
nternuclear opthalmoplegia:
medial longitudinal fasciculus connects CN nucleus 3-4.
Ipsilateral adduction palsy, contralateral nystagmus.
Aide memoire (TRIES TO YANK
THE ipsilateral BAD eye ACROSS THE nose ). Convergence retraction nystagmus, but convergence reflex is normal. Causes: MS, SLE, Miller fisher, overdose(barb, phenytoin, TCA), Wernicke.
Progressive Supranuclear palsy:
Steel Richardson. Absent voluntary downward gaze, normal dolls eye . i.e. Occulomotor nuclei intact, supranuclear Pathology .
Wheeles, URTICARIA , drug induced →
aspirin.
.Causes of SIADH : c
chest/cerebral/pancreas Pathology , porphyria, malignancy, Drugs
(carbamazepine, chlorpropamide, clofibrate, atipsychotics, NSAIDs, rifampicin, opiates)
Returned from airline flight, TIA→
paradoxical embolus do TOE.
Alcoholic, given glucose develops nystagmus →
B1 deficiency (wernickes).
Painful 3rd nerve palsy →
posterior communicating artery aneurysm till proven
otherwise
Late complication of scleroderma →
pulmonaryhypertention plus/minus fibrosis.
Vomiting, abdominal pain, hypothyroidism →
Addisonian crisis (TFT typically
abnormal in this setting DO NOT give thyroxine).
Mouth/genital ulcers and oligarthritis →
behcets (also eye /SKIN lesions, DVT)
.Cavernous sinus syndrome -
3rd nerve palsy, proptosis, periorbital swelling, conj
injection
