Speciality Medicine

Speciality Medicine

Speciality Medicine

🦠 Infectious Disease

‣
🧫 Understanding Bacteria

We classify bacteria into the following:

‣
Gram ⊕ (peptidoglycan cell wall)
‣
What colour do they turn on gram staining?
  • Purple/blue as the cell wall binds to the molecules in the crystal violet stain.

‣
Cocci (spherical/round)
‣
Staphylococci (+ catalase)
‣
S. aureus (+ coagulase)
‣
S. epidermis (- coagulase)
  • Central line infections
‣
Streptococci (- catalase)
‣
α-haemolytic: Partial haemolysis
  • S. pneumonia
  • S. viridans
‣
β-haemolytic: Complete haemolysis
  • Group A: S. pyogenes
    • ‣
    Name 4 infections that the bacteria can cause.
    1. Erysipelas
    2. Impetigo
    3. Cellulitis
    4. Tonsillitis
  • Group B: S. agalactiae
‣
γ-haemolytic: No haemolysis
  • Enterococci
‣
Bacilli (rods)
  • Mycobacteria
  • Corneybacteria
  • Bacillus
  • Nocardia
  • Listeria monocytogenes
‣
Anaerobes
  1. Clostridium (KEY - C. difficile)
  2. Lactobacillus
  3. Actinomyces
  4. Propionibacterium
‣
Gram ⊖
‣
What colour do they turn on gram staining?
  • No reaction to the crystal violet stain as they don’t have a cell wall.
  • Safranin stain turns them red, binding to the cell membrane.

‣
Diplococci (rounded bacteria occurring in pairs)
  1. N. meningitidis
  2. N. gonorrhoea
  3. Moraxella
‣
Coccobacilli (in between)
  1. Haemophilus influenzae
  2. Bordatella pertussis
‣
Bacilli (rod)
  1. E. coli
  2. Pseudomonas
  3. Enterobacteriae:
    1. Klebsiella
    2. Salmonella
    3. Shigella
    4. Campylobacter
    5. V. cholera
‣
Atypical
  1. Legionella
  2. Mycoplasma pneumoniae
  3. Chlamydia psittaci
  4. Chlamydydophila pneumoniae
  5. Q fever: Coxiella burneti
‣
🧪 Antibiotics
‣
Name the 4 ways that antibiotics commonly kill bacteria.
  1. Inhibition of cell wall synthesis
    2. ‣
    How can we classify these further?
    1. With a beta-lactam ring
      2. ‣
      Name 3 examples of these.
      1. Penicillins (e.g. amoxicillin)
      2. Carbapenems (e.g. meropenem)
      3. Cephalosporins (e.g. cefotaxime)
    2. Without a beta-lactam ring
      3. ‣
      Name 2 examples of these.
      1. Vancomycin
      2. Teicoplanin
    ‣
    What type of bacteria do we use these to treat?
    • Gram ⊕ as they have a peptidoglycan cell wall
    ‣
    What percentage of people with a documented ‘penicillin allergy’ have a true allergy?
    • 10% — Ask what the reaction is. If not rash and angioedema, likely not a true allergy.
  2. Inhibition of folic acid metabolism
    3. ‣
    Name 2 examples of antibiotics that use this mechanism.
    1. Trimethoprim
    2. Co-trimoxazole
  3. Inhibition of nucleic acid synthesis
    4. ‣
    What antibiotic uses this mechanism of action?
    1. Metronidazole: Only effective within anaerobic organisms, not effective against aerobic organisms.
  4. Inhibition of protein synthesis (targeting the ribosome)
    5. ‣
    Name 4 examples of antibiotics that use this mechanism.
    1. Macrolides (e.g. clarithromycin)
    2. Clindamycin
    3. Tetracyclines (e.g. doxycycline)
    4. Gentamicin
‣
What antibiotic would you choose to cover the following bacteria:
‣
Pseudomonas
  • Tazocin
‣
Atypical bacteria
  • Doxycycline / clarithromycin
‣
MRSA
  • Vancomycin / teicoplanin
‣
E. coli
  • Co-amoxiclav
‣
Streptococci
  • Amoxicillin
‣
ESBL (extended-spectrum beta-lactamases)
  • Meropenem
‣
🤧 Common Infections

Systemic:

‣
Sepsis
‣
What’s the pathophysiology?
  1. Macrophages, lymphocytes and mast cells recognise bacteria → Cytokine release (TNF, IL)
    1. Cytokines → Nitrous oxide release → Vasodilation
    2. Cytokines → ↑ blood vessel permeability → Oedema & ↓ intravascular volume
  2. Coagulation activation → ↑ platelet & clotting factor consumption → thrombocytopenia & inability to form clots
    3. ‣
    What is this called?
    • Disseminated intravascular coagulopathy (DIC)
  3. Tissue hypoperfusion → Anaerobic respiration
    4. ‣
    How do we measure for tissue hypoperfusion
    • Lactate: Lactic acid is the product of anaerobic respiration.
‣
How would we investigate a septic patient?
  • Bedside:
    • Urinalysis +/- Urine MC&S
    • Lumbar puncture
  • Bloods:
    • FBC: WCC, neutrophils
    • CRP: Inflammation
    • Blood culture: Bacteraemia
    • U&Es: AKI
    • LFTs: Source? (? Cholangitis, ? Cholecystitis)
    • Clotting: DIC to assess for disseminated intravascular coagulopathy (DIC)
    • VBG/ABG: Lactate
  • Imaging (depends on presenting symptoms & signs):
    • CXR: Chest
    • CT abdomen: Abdominal
‣
When would we classify them as being in septic shock?
  • Systolic blood pressure < 90 mmHg (& not responding to fluid resuscitation)
  • ↑ lactate > 4 mmol/L

Management:

‣
What are the immediate management steps for sepsis? (Sepsis 6)

Remember: BUFALO OR 3 in 3 out.

  • Blood cultures
  • Urine output → Urinary catheter (Is it < 0.5 ml/kg/hr?)
  • Fluids (IV) → Fluid challenge (500ml NaCl (0.9%) over 15 mins)
  • Antibiotics (IV) → The choice depends on the cause, severity and local guidelines.
  • Lactate → VBG (if they’re not desaturating) / ABG (if they’re desaturating)
  • Oxygen
‣
What is the first-line empirical antibiotic for neutropenic sepsis?
  • Tazocin (piperacillin & tazobactam)
‣
What score is used to categorise and grade sepsis patients?
  • qSOFA / SOFA score

Bacterial:

‣
Cellulitis
‣
Name the two organisms that commonly cause this.
  • S. aureus
  • S. pyogenes
‣
Cases
‣
A patient presents with severe leg pain, it is erythematous and very swollen. Pain is out of keeping with physical features. What is the potential diagnosis and management of this?
  • Necrotising fasciitis
  • IV antibiotics and surgical debridement of necrotic tissue
‣
A 57 year old patient has a painful butterfly rash that is sharply demarcated across the bridge of the nose & cheeks. She had a 2 week history of coryzal symptoms prior to this. Diagnosis? Organism?
  • Erysipelas caused by S. pyogenes infection.
‣
A patient is bitten by a dog, how is this managed?
  • IV co-amoxiclav
    • Penicillin allergic: Doxycycline & metronidazole
‣
Management
‣
What is the management if there are no signs of systemic toxicity?
  1. PO flucloxacillin
  2. Penicillin allergic: Clarithromycin
‣
What is the management if there is systemic toxicity?
  • Admission to hospital for full assessment
  • IV Co-amoxiclav
‣
How would you treat MRSA cellulitis?
  • Vancomycin
    • ‣
    After initiating a rapid vancomycin infusion, the patient develops a red rash, pruritus and a burning sensation in their upper body. Vitals are normal. Differentials? Management?
    • Differentials:
      • Red man syndrome (normal vitals make this more likely)
      • Anaphylaxis
    • Management: Stop the infusion and restart later at a slower rate
‣
Gastroenteritis
‣
What bacteria have the following incubation periods:
‣
1-6 hours
  • Bacillus cereus
  • S. aureus
‣
12-48 hours
  • Salmonella
  • E. coli
  • Norovirus
‣
48-72 hours
  • Campylobacter
  • Shigella
‣
Name 3 complications that can follow gastroenteritis.
  1. Guillian-Barré syndrome
  2. Reactive arthritis
  3. Lactose intolerance (Giardiasis)

Cases:

‣
A patient being treated for an infective exacerbation of COPD has developed profuse watery diarrhoea. Diagnosis?
  • C. dificile infection
    • ‣
    What is the management?
    1. IV fluids & PO metronidazole
    2. Severe: IV vancomycin
‣
A patient drunk contaminated water on holiday and now has abdominal cramps, bloody diarrhoea & vomiting. Cause?
  • E. coli 0157 producing Shiga toxin
    • ‣
    When bloods are taken she has high creatinine, low Hb and low platelets. What has she now developed?
    • Haemolytic uraemic syndrome
    ‣
    Should patients with E. coli gastroenteritis be given antibiotics?
    • No, it increases the risk of HUS
‣
A patient ate shellfish in India 2 days ago, now has profuse diarrhoea causing him to collapse and OE he is hypoglycaemic. No blood in diarrhoea. Diagnosis?
  • Cholera - Rapid descent into hypovolaemia, acidosis & death.
    • ‣
    How are they managed?
    1. IV fluids
    2. Doxycycline / Co-trimoxazole
‣
A patient had flu-like symptoms 3 days ago followed by crampy abdominal pain, fever and bloody diarrhoea after eating chicken. Cause?
  • Campylobacter jejuni
    • ‣
    How are they managed?
    1. Mostly conservative
    2. Severe: Azithromycin / ciprofloxacin
    ‣
    What complication can occur from this?
    • Guillian-Barré syndrome
‣
A patient presents with vomiting following eating rice left out from the night before. Cause?
  • Bacillus (Gram positive rod)
‣
Patient presents with headache, fever, arthralgia and Rose spots, mum says he may have eaten something 'dodgy'. Diagnosis?
  • Salmonella typhi gastroenteritis - Typhoid
    • ‣
    How is this managed?
    • Ciprofloxacin (Salmonella & Shigella)
‣
Urinary tract infection (UTI)

UTI can be split into:

‣
Cystitis: Infection of the bladder.
‣
Why is this more common in women?
  • Shorter urethra.
‣
How do they present?
  1. Dysuria
  2. Suprapubic pain
  3. Urinary urgency / frequency / incontinence
‣
What would you look for on urinalysis?
  1. Nitrites: Suggests presence of bacteria as they break down nitrates in the urine into nitrites.
  2. Leukocytes: The number of white cells in the urine.
‣
Management:

Name the management options and durations for:

‣
A non-pregnant woman with a UTI.
  • Trimethoprim → 3 days
  • Nitrofurantoin → 3 days
    • ‣
    When would you choose trimethoprim over nitrofurantoin?
    • Reduced renal function: Nirtofurantoin reaches the bladder via the kidneys, therefore in reduced renal function, it will not reach its destination.
‣
A pregnant woman in the first trimester with a UTI.
  • Nitrofurantoin → 7 days
    • ‣
    Why not use trimethoprim?
    • It’s teratogenic.
‣
A pregnant woman in the third trimester with a UTI.
  1. Amoxicillin (only if culture results available and susceptible) → 7 days
  2. Cefalexin → 7 days
‣
A man with a UTI.
  • Trimethoprim → 7 days
‣
Asymptomatic UTI in a catheterised patient.
  • No management needed until symptomatic
‣
Pyelonephritis: Escalation of the infection into the kidney
‣
How do they present?
  1. Fever
  2. Haematuria
  3. Back pain
  4. Vomiting
  5. Loss of appetite
  6. OE: Renal angle tenderness
‣
What antibiotic course would you opt for?

A 7-10 day course of:

  1. Cefalexin or
  2. Co-amoxiclav or
  3. Trimethoprim.
‣
Bacterial Vaginosis
‣
What is the pathophysiology?
  • Overgrowth of anaerobic bacteria → ↓ Aerobic bacteria producing lactic acid → ↑ Vaginal pH
‣
What organism causes it?
  • Gardnerella vaginalis
‣
Name 4 characteristic features of BV.
  1. Thin, white discharge (fishy)
  2. Clue cells on microscopy
  3. Vaginal pH > 4.5
  4. Positive whiff test (add KOH → fishy odour)
‣
How is it managed? Different in pregnancy?
  • PO Metronidazole 5 days
  • No
‣
What risk does it pose in pregnancy?
  • Premature rupture of membranes (PROM)
‣
Tetanus
‣
How is tetanus often contracted?
  • Exposing a wound to contaminated soil
‣
The toxin released by tetanus prevents GABA release, what symptoms does this cause?
  • Muscle spasms (e.g. dysphagia)
  • Lock jaw
‣
How are they managed?

Confirmed tetanus:

  1. IV tetanus immunoglobulin

Tetanus-prone wounds:

  1. IM tetanus immunoglobulin (for high risk wounds) & dose of Td/IPV vaccine
  2. Arrange full tetanus course
‣
How many doses are required in the tetanus vaccination schedule?
  • 5

Viral:

‣
Herpes simplex virus
‣
Name three signs of infection with HSV. How are each of these managed?
  • Genital ulcers
    • ‣
    Management?
    • PO aciclovir
  • Gingivostomatitis
    • ‣
    Management?
    • PO aciclovir
  • Cold sores
    • ‣
    Management?
    • Topical aciclovir
‣
If a woman has a primary attack in pregnancy how is it managed?
  • Elective C-section (if > 28 weeks) & PO aciclovir
‣
How is a woman with recurrent herpes managed in pregnancy?
  • PO aciclovir
‣
Glandular Fever
‣
What is the cause of this in 90% of cases?
  • EBV
‣
What is the classic triad of infectious mononucleosis?
  1. Pyrexia
  2. Lymphadenopathy
  3. Sore throat
‣
Name 3 other features that these patients may have.
  1. Palatal petechiae
  2. Splenic rupture
  3. Cold AIHA
‣
How is the diagnosis confirmed?
  • Monospot test
  • Specific salivary IgM
‣
How is it managed?
  • Supportive
‣
Complications:
‣
Name 2 types of lymphoma associated with EBV.
  1. Burkitt's
  2. Hodgkin's
‣
What other cancer is it associated with?
  • Nasopharyngeal carcinoma
‣
🌴 Tropical Infections

Not comprehensive, only high yield topics:

‣
HIV
‣
How is it transmitted?
  • Horizontal:
    • Membrane: Sexual contact (vaginal, oral, anal)
    • Blood/wound exposure to infected bodily fluids or blood (e.g. needle stick injuries & sharing needles)
  • Vertical: Pregnancy, birth, breastfeeding
‣
How does HIV affect the immune system?
  • HIV (RNA retrovirus) enters the & destroys CD4+ T-helper cells → Immunocompromise

Presentation:

‣
How can they present?
  • Fever
  • Headache
  • Muscle aches and joint pain
  • Rash: Seborrhoeic dermatitis, atopic dermatitis
  • Infections: Sore throat and painful mouth sores, diarrhoea, lymphadenopathy
  • Weight loss
  • Cough
  • Night sweats

Investigations:

‣
How long after the exposure do you have to wait until you can test?
  • 1 month
‣
If this test is negative, do you need to do a second test? If so, when?
  • Yes - 3 months after exposure
‣
How do you test for HIV? (3)
  1. HIV antibody test (commonly used)
  2. P24 antigen test (benefit of this is it can be picked up earlier)
  3. HIV viral load via PCR testing

Management:

‣
A patient is diagnosed with HIV, when should antiretroviral therapy be initiated? Is CD4 count relevant?
  • Immediately: CD4 count not relevant
‣
What makes up 'Highly active antiretroviral therapy (HAART)'?
  1. 2 NRTIs (nucleoside reverse transcriptase inhibitors)
  2. 1 PIs (protease inhibitor - ...navir drugs)
‣
How do you monitor the effectiveness of treatment?
  1. Viral load (Ideally ↓/undetectable)
  2. CD4+ count (Ideally ↔︎)
‣
A HIV positive patient is pregnant. How do you manage this patient to reduce vertical transmission risk to the foetus? (3)
  1. Maternal & neonatal antiretroviral therapy
  2. C-section
  3. Infant bottle feeding

Needle stick:

‣
If you get a needle stick from a HIV positive patient what is the management?
  1. Wash & bleed
  2. PO antiretroviral therapy (within 72 hrs) for 4 weeks
    3. ‣
    If you get a needle stick from a HIV positive patient, what is the probability you will get infected?
    • 0.3%
      • ‣
      What's the transmission rate in HepB & HepC needle sticks?
      • HepB: 20-30%
      • HepC: 0.5-2%

Complications:

‣
Infectious (High-yield)
‣
HIV patient presents with exertional dyspnoea, dry cough and fever. What is your main differential?
  • Pneumocystis jiroveci pneumonia
    • ‣
    How can you investigate this to confirm your differential? (3)
    1. CXR - Bilateral interstitial pulmonary infiltrates
    2. Exercise-induced desaturation (↓ SpO₂)
    3. Histology: Sputum or biopsy then do silver stain or toludine blue will show the cysts
    ‣
    What is the management? (2)
    1. Co-trimoxazole
    2. IV pentamidine
‣
A HIV patient presents with diarrhoea. What is the most common cause of diarrhoea in HIV patients?
  • Cryptospordiosis
‣
Man presents with abnormal movements and a hypodense area in the basal ganglia. CSF shows raised protein but the rest is normal. Diagnosis?
  • Progressive multifocal leukoencephalopathy (PML) - caused by JC virus
‣
A HIV patient has symptoms of meningitis. What organism do you need to consider?
  • Cryptococcus (fungal)
    • ‣
    Investigations?
    • India stain
    • High opening pressure on LP
‣
HIV patient presents with a hard white lesion on the tongue that looks like candidiasis but can’t be rubbed off. What is this?
  • Hairy leukoplakia
    • ‣
    How do you differentiate between hairy leukoplakia and oral candidiasis?
    • Hairy leukoplakia cannot be scraped away from the tongue, candidiasis can.
    ‣
    What is the underlying pathogen causing this?
    • EBV
‣
Neoplastic
‣
A HIV patient presents with headache, confusion and drowsiness. What are your two differentials?
  1. Toxoplasmosis
  2. Primary CNS lymphoma
    3. ‣
    What is the cause of lymphoma in these patients?
    • EBV
    ‣
    How do you differentiate between the two?
    1. Toxoplasmosis
      • Multiple lesions
      • Ring/nodular enhancement
    2. CNS lymphoma
      • Single lesion
      • Solid (homogenous) enhancement
    ‣
    How do you manage each, respectively?
    1. Toxoplasmosis: Sulfadiazine & pyrimethamine
    2. Lymphoma: Dexamethasone, chemotherapy, radiotherapy, surgical excision
‣
A HIV patient presents with the following skin lesions:
‣
What is this?
  • Kaposi sarcoma
‣
What is the cause?
  • Herpes (HHV-8) on background of HIV infection
‣
Where can it present?
  • Skin
  • GI tract
  • Respiratory - Haemoptysis / Pleural effusion
‣
Management?
  • Radiotherapy & resection
OpenStax College, CC BY 3.0
OpenStax College, CC BY 3.0 creativecommons.org/licenses/by/3.0, via Wikimedia Commons. No changes were made.
‣
Tuberculosis

Presentation:

‣
How effective is the bCG vaccination? Name 3 contraindications.
  • Not very effective.
  • Contraindications:
    1. Past TB infection
    2. Pregnancy
    3. Immunosuppression
‣
A patient has been recently diagnosed with TB and has innumerable small spots across the lungs on CXR. What is this suggestive of?
  • Miliary TB
    • ‣
    Which area of the lungs is commonly affected first?
    • Apex of lungs
    ‣
    How has the infection spread from the ghon focus?
    • Pulmonary venous system
    ‣
    Name 2 other manifestations of secondary TB.
    • Meningitis
    • Pott's disease: Vertebral bodies affected

Investigations:

‣
Name the main test used in the diagnosis of TB. How does it work? What is a positive result? When can you get false negative results?
  • Mantoux test: Inject tuberculin into forearm → Look for reaction
    • ≥ 6mm → Positive result.
  • False negatives in: Miliary TB, HIV, sarcoidosis, lymphoma
‣
If you get a false negative result, what other test can be done?
  • Interferon-gamma blood test
‣
The tissue is biopsied. What pathological test is done? What is a positive result?
  1. Ziehl-Neelsen stain / Auramine staining
  2. Positive result: Acid fast bacilli

Management:

‣
How do you manage this over the next 6 months? (High-yield)

2 months:

  1. Rifampicin
    2. ‣
    Side effects?
    • Orange secretions
    • CYP450 inducer
  2. Isoniazid
    3. ‣
    Side effects?
    • Peripheral neuropathy
    ‣
    What can be given with this to minimise SEs?
    • Pyridoxine
  3. Pyrazinamide
    4. ‣
    Side effects?
    • Gout
    • Hepatotoxicity
  4. Ethambutol
    5. ‣
    Side effects?
    • Optic neuritis/neuropathy
    ‣
    What test is needed before initiating this?
    • Check visual acuity

Subsequent 4 months: Rifampicin & isoniazid

‣
Malaria
‣
How do they present?
  1. Fever on-and-off for alternating days
  2. Headache, myalgia, hepatomegaly
  3. History of foreign travel
‣
How is this transmitted?
  • Mosquitos
‣
Name 2 protective factors against malaria.
  • Sickle cell
  • G6PD deficiency
‣
Name the 2 types. Which is more common? Which is more severe? (Follow-on Qs)
  1. Falciparum (More common & more severe)
    2. ‣
    How do you diagnose this?
    • Blood film: Schizonts
    • Parasitaemia > 2%
  2. Non-falciparum
‣
How is uncomplicated malaria managed?
  • Artemisinin-based combination therapies
‣
How is severe malaria managed?
  • IV artesunate
‣
Tropical Viruses

The following patients have returned from a holiday in a tropical country:

‣
Patient presents with a retro-orbital headache, fever, facial flushing and bloods show ↑ ALT. Diagnosis? Transmission? Management?
  • Dengue fever
  • Mosquito
  • Supportive
‣
A week ago, patient describes they had a high fever, rigors and N&V. They felt better for the last few days but now have thrown up blood and are jaundiced. Diagnosis? Transmission? Management?
  • Yellow fever
  • Mosquito
  • Supportive
‣
Patient presents with fever, fatigue and headache followed by D&V and rash. Diagnosis? Transmission?
  • Ebola virus
  • Touching mucous membranes/secretions from infected individuals (clothes, etc.)
‣
Why are these patients predisposed to severe bleeding?
  • Viral haemorrhagic fever (DIC)
‣
Rare infection cases:
‣
A 23 year old woman has recently returned from a lake resort holiday in Africa and has fever, malaise, dry cough, diarrhoea and right upper quadrant pain. She is pyrexic and has an urticarial rash & hepatosplenomegaly. Diagnosis?
  • Schstosomiasis (parasite)
    • ‣
    Management?
    • Praziquantel: Kills adults but not eggs (Give now and after 3 months)
    • Steroids: Suppress hypersensitivity
‣
Patient returns from holiday with abdominal pain & diarrhoea alongside a cough and fever. They have maculopapular rose spots that blanch on pressure. Diagnosis?
  • Typhoid
    • ‣
    What organism causes it?
    • Salmonella typhi
    ‣
    What do FBC & LFT show?
    • FBC: Neutropenia
    • LFT: Raised transaminases
‣
A patient from India presents with hypopigmented hypoesthetic patches of skin and a change in their facial appearance. Diagnosis?
  • Leprosy
    • Hypopigmented: Loss of pigmentation of skin
    • Hypoesthesia: Sensory loss in areas of lost pigment. Thickened peripheral nerves.
      • ‣
      How is it managed?
      • Dapsone, rifampicin and clofazimine for 12-24 months
‣
A patient presents with a ‘bullseye rash’ (erythema migrans). What is this suggestive of?
  • Lyme Disease (Borelliosis)
    • ‣
    How is this spread?
    • Ticks
    ‣
    Name 2 neurological manifestations.
    • Peripheral neuropathy, e.g. facial nerve palsy (can be bilateral)
    • Meningitis
    ‣
    How do you investigate for it?
    • Blood test for ELISA serology
    ‣
    How is it managed in both early and disseminated disease?
    • Early: PO doxycycline
    • Disseminated: Ceftriaxone

Ltshears, CC BY-SA 3.0
Ltshears, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
A patient has been bit by a dog, and now is hypersalvating and has muscle spasms. Diagnosis?
‣
A sewage worker has bilateral conjunctivitis, bilateral calf pains and a high fever. Diagnosis?
  • Leptospirosis
    • Also seen in farmers & vets
    • Renal failure in 50%, liver failure in 10%
      • ‣
      Management?
      • High dose benzylpenicillin / doxycycline
‣
🍆 Sexually Transmitted Infections
‣
Ulcers
‣
Patient presents with multiple painful ulcers around her vagina. Likely diagnosis?
  • HSV
    • ‣
    What are the differentials & features of them?
    • Chancroid: Tropical disease (travel history), unilateral tender lymphadenopathy
    • LGV: Small painless pustule → Ulcer → Painful inguinal lymphadenopathy → Proctocolitis (bowel symptoms)
    ‣
    How is this managed?
    • PO aciclovir
‣
Patient presents with a single painless ulcer. Serological tests show ✅VRDL and ✅TPHA. Diagnosis? (Follow-on Qs)
  • Syphilis
    • ‣
    What causes this?
    • Treponema pallidum
    ‣
    What is the first-line management?
    • IM benzylpenicillin
    ‣
    Patient presents with fever, rash and tachycardia following their first dose of this. What reaction is this? Worrying?
    • Jarisch-Herxheimer reaction
    • Not worrying, may need antipyretics
    ‣
    Following treatment, what will the serological tests show?
    • ❌VRDL
    • ✅TPHA
‣
A patient is diagnosed with chlamydia and also has an ulcer on his penis and painful inguinal lymphadenopathy. Likely diagnosis? Management?
  • LGV
  • Management: Doxycycline
‣
A patient has arrived back from Kenya with multiple eroded genital ulcers, he is systemically well and culture grew Haemophilus ducreyi. Diagnosis?
  • Chancroid
‣
Warts
‣
What causes these?
  • HPV
‣
What are the 2 different types of warts and how does their management differ?
  • Solitary, keratinised: Cryotherapy
  • Multiple, non-keratinised: TOP podophyllum
‣
Trichomoniasis
‣
What vaginal discharge is seen in this?
  • Frothy yellow/green
‣
How is it diagnosed?
  • Swab & microscopy
‣
How is it managed?
  • PO Metronidazole 5-7 days
‣
Chlamydia
‣
How long after exposure do you have to wait until you test for this?
  • 2 weeks
‣
How is it investigated? Does it differ in women and men?

NAATs - Nuclear acid amplification tests

  • Men: First-catch urine sample
  • Women: Vulvovaginal swab
‣
Patient presents after their partner told them they have chlamydia. How is this managed?
  • Treat then test
‣
What is the first-line management?
  • Azithromycin - Single dose
‣
Name 3 complications of chlamydia.
  1. PID → Infertility
  2. Epididymitis
  3. Reactive arthritis (Reiter's)
‣
Gonorrhoea
‣
What are the bacteria's characteristics on microscopy?
  • Gram negative diplococci
‣
How do they often present?
  • Discharge from genitalia
  • Dysuria
  • Dermatitis
  • Arthritis
  • Tenosynovitis (synovial membrane inflammation)
‣
How are they managed?
  • IM ceftriaxone

🧫 Haematology

‣
💉 Anaemia

Name the causes of each of the following:

‣
Microcytic anaemia
‣
Thalassaemia
‣
What are the types?
‣
ɑ
  • 4 genes, they need at least one functional copy to be compatible with life
  • Symptomatic when they have ≥ 2 copies
‣
β
  1. Minor: Heterozygous
  2. Intermedia
  3. Major: Homozygous
    4. ‣
    How does this present?
    • Failure to thrive in the first year of life
    • Microcytic anaemia
‣
What facial features may these patients have?
  1. Prominent forehead
  2. Prominent cheek bones
‣
What are the signs on blood film?
  • Marked poikilocytosis (speculated tear‐drop cells)
  • Target cells
  • Numerous erythroblasts
‣
How would you manage them?
  1. Regular blood transfusions: Provide healthy, functional RBCs → Prevents intrinsic, dysfunctional erythropoiesis
  2. Iron chelation therapy (e.g. desferrioxamine) to prevent iron overload
‣
Anaemia of chronic disease

See normocytic, can be microcytic or normocytic.

‣
Iron deficiency anaemia
‣
Name 4 causes of iron deficiency.
  1. Menorrhagia
  2. GI bleed
  3. Low dietary intake
  4. Malabsorption, e.g. Crohn's/Coeliac
‣
Name 7 features of iron deficiency.
  1. Shortness of breath
  2. Fatigue
  3. Palpitations
  4. Koilonychia
  5. Conjunctival pallor
  6. Angular stomatitis
‣
Why may they be struggling to swallow?
  • Oesophageal webs (Plummer-Vinson syndrome)

Investigations:

‣
What is the classic FBC picture in iron deficiency?
  1. Microcytic anaemia
  2. ↓ MCHC (Hypochromia)
  3. ↑ RDW (Anisocytosis)
‣
On iron studies, what would the ferritin, TIBC and transferrin saturation be?
  • ↓ Ferritin (although this is an acute phase reactant so could be normal)
  • ↑ Total iron binding capacity
  • ↓ Transferrin saturation

Management:

‣
What is the transfusion threshold in a patient with & without ACS?

Transfuse the patients if they have a Hb (but check local guidelines):

  • ACS < 80 g/L
  • Without ACS < 70 g/L
‣
Lead poisoning
‣
In what symptoms should this be considered?
  • Abdominal pain & neurological symptoms combined
  • Blue lines on gum margins
‣
Ultimately, what does lead poisoning lead to? What can be seen on investigations because of this?
  • Inability to produce haem → Microcytic anaemia
‣
What is a differential?
  • Intermittent porphyria
‣
Siderblastic anaemia
‣
What is this?
  • Ineffective erythropoiesis → ↑ iron absorption & deposition in bone marrow, liver, heart & endocrine organs
‣
What are the causes?
  1. Congenital: Inherited in many different ways
  2. Drugs: Alcohol, lead poisoning, isoniazid
‣
What is seen on FBC & iron studies?
  • Microcytic anaemia
  • ↑ Ferritin
  • ↑ Iron
‣
What is seen on blood film?
  • Pappenheimer bodies
‣
Normocytic anaemia
‣
Acute blood loss

Blood loss may cause anaemia (but may not initially), if the patient has sufficient iron stores to maintain normal red cell output then it will be normocytic.

‣
Anaemia of chronic disease
‣
Why does this occur?
  • Chronic disease/inflammation → IL-6 release → ↑ hepcidin → ↓ Fe absorption
‣
How does the FBC change over time?
  1. Initially: Normocytic, normochromic
  2. Long-term: Microcytic, hypochromic
‣
What would Fe studies show?
  • ↓ TIBC
  • ↑ Ferritin (acute phase reactant)
‣
How do you differentiate between a mixed micro/macro anaemia and anaemia of chronic disease?
  • ↑ RDW: Red cell distribution width will be increased due to a combination of both macrocytes and microcytes, that average out to be normocytic
  • ↑ Ferritin: High because it is an acute phase reactant so stimulated by disease activity
‣
Name an example of when a mixed micro/macro presentation may occur.

Crohn's disease

  • Micro: Fe deficiency due to blood loss from chronic bleeding.
  • Macro: Low B12 absoption due to terminal ileum inflammation.
‣
Aplastic anaemia
‣
What are the key features?
  • ↓ Hb
  • ↑ reticulocytes
‣
What are the causes?
  1. Idiopathic
  2. Congenital: Fanconi anaemia, dyskeratosis congenita
  3. Drugs: Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
  4. Infections: Parvovirus, hepatitis
  5. Radiation
  6. Leukaemia: ALL, AML
‣
Haemolytic anaemia

Types:

‣
Inherited
‣
Hereditary spherocytosis
  • Autosomal dominant inheritance
  • Defect in the erythrocyte membrane → Breakdown by splenic macrophages
  • Aplastic crisis in parvovirus infection
  • Management: Splenectomy
‣
G6PD deficiency
‣
How is it inherited?
  • X-linked recessive
‣
What is the pathophysiology? (2)
  • ↓ G6PD → Oxidative RBC stress → Intravascular haemolysis
‣
What is the classic presentation?
  1. Trigger: Patient ate fava beans, got an infection or started on antimalarial
  2. Result: Develop jaundice & anaemia following this
‣
Name 3 features.
  1. Neonatal jaundice (High prevalence in African, Asian & Mediterranean people)
  2. Splenomegaly
  3. Heinz bodies (blood film)
‣
What investigation gives a definitive diagnosis?
  • G6PD enzyme assay
‣
What drugs can trigger haemolysis?
  • Sulph-drugs: Sulphonamides, sulphasalazine, sulfonylureas
  • Ciprofloxacin
  • Anti-malarials: primaquine
‣
How do you differentiate from hereditary spherocytosis?
  • Gender: G6PD only males
  • Blood film: G6PD Heinz bodies
‣
How are they managed?
  1. Folate supplementation: ↑ RBC production
  2. Consider splenectomy
‣
Sickle cell
‣
Basics
‣
How is it inherited?
  • Autosomal recessive
‣
What is the pathophysiology? (4)
  1. Decreased water solubility of deoxy-Hb
  2. HbS polymerisation → RBC sickle
  3. Sickle cells are fragile → Haemolysis → Blocking of small blood vessels → Infarction
‣
When are homozygotes likely to present?
  • 4-6 months → This is when foetal haemoglobin degrades and they rely on their own
‣
Investigations
‣
How are they investigated initially?
  1. FBC - Microcytic anaemia, reticulocytosis
  2. LFT: Unconjugated hyperbilirubinaemia
  3. Blood film: Sickle cells, target cells, reticulocytes, Howell-Jolly bodies
‣
What is the diagnostic test?
  • Haemoglobin electrophoresis +/- genetic testing
‣
Why might they have Howell-Jolly bodies on blood film?
  • Splenic infarction → Hyposplenism → Howell-Jolly bodies
‣
Name the 5 sickle cell crises.
‣
Vaso-occlusive
‣
Where does this commonly affect (in exams)?
  • Priapism (painful, persistent erection) requiring aspiration of blood
‣
Splenic sequestration: Pooling of blood in the spleen
‣
What does this cause?
  • Severe anaemia
  • Hypovolaemic shock
‣
What can recurrent crises lead to?
  • Splenic infarction
‣
Acute chest syndrome: Dyspnoea, chest pain
‣
What features are required for this? (2)
  1. Fever/respiratory symptoms
  2. New infiltrates on CXR
‣
What causes this?
  1. Infective: Pneumonia/bronchiolitis
  2. Non-infective: Pulmonary vaso-occlusion/fat emboli
‣
Aplastic
‣
What is this?
  • Failure of the bone marrow to produce any RBCs
‣
What infection commonly causes it?
  • Parvovirus B19
‣
Haemolytic

This is rare, Hb drops due to increased haemolysis

‣
Management
‣
How are they managed generally?
  1. Avoid dehydration
  2. PenV prophylaxis
  3. Pneumococcal polysaccharide vaccine every 5 years
‣
A patient has recurrent painful crises, what medication may be helpful?
  • Long-term hydroxyurea (stimulates HbF)
‣
How are sickle cell crises managed?
  • Supportive
    • Treat infection, keep warm, hydrated, analgesia
    • Antibiotics if required
    • Exchange transfusions
‣
Thalassaemia

See microcytic anaemia.

‣
Acquired
‣
Autoimmune haemolytic anaemia (AIHA)
‣
How do you test for it?
  • Direct coombs test

Two types:

‣
Warm AIHA
‣
Where is the haemolysis?
  • Extravascular: Spleen tags cells for phagocytosis
‣
What are the causes?
  • CLL
  • Lymphoma
  • SLE
‣
How is it managed?
  • Steroids: Immunosuppression is effective
‣
Cold AIHA
‣
Where is the haemolysis & what are the causes?
  • Intravascular: IgM causes complement to directly break down RBCs
‣
What are the causes?
  1. Mycoplasma
  2. EBV
  3. Lymphoma
‣
What investigation confirms this?
  • Cold agglutinins (IgM-complement complexes)
  • ↓ serum haptoglobins
‣
How is it managed?
  • Treat the underlying infection
  • Immunosuppression is less effective compared with warm AIHA
‣
Non-immune

Causes:

  1. Transfusion reactions
    2. ‣
    How do you manage a haemolytic reaction?
    • Stop immediately & flush line
    ‣
    How do you manage a febrile non-haemolytic reaction?
    • Slow transfusion & give paracetamol
    ‣
    If a patient has a minor allergic reaction to a blood transfusion, how is it managed?
    • Temporarily stop & antihistamine
  2. Mechanical (e.g. metallic heart valve)
  3. Microangiopathic haemolytic anaemia
    4. ‣
    What are the causes?
    1. HUS: Haemolytic uraemic syndrome
      • Triad: Microangiopathic haemolytic anaemia + thrombocytopenia + AKI
      • Schistocytes on blood film
    2. DIC: Disseminated intravascular coagulation
    3. TTP: Thrombotic thrombocytopaenic purpura
  4. Paroxysmal nocturnal haematuria
    5. ‣
    What is this?
    • Complement system attacks the RBCs due to receptor mutation
    ‣
    What is the typical presentation?
    1. Haematuria in the morning
    2. Predisposed to thrombosis (DVT/PE)
    3. Smooth muscle dystonia
  5. Infectious: Malaria
    6. ‣
    What would you seen on blood film?
    • Plasmodium schizonts
      • Lukas.S at English Wikipedia, Public domain, via Wikimedia Commons
      Lukas.S at English Wikipedia, Public domain, via Wikimedia Commons
  6. Hypersplenism (e.g. in liver cirrhosis)

Investigations:

‣
What bloods would you do and what results would you look for?
  1. FBC
    • Normocytic anaemia
    • ↑ reticulocytes
  2. Blood film:
    • Spherocytes
    • Schistocytes
    • Sickle cells
  3. LDH
  4. LFT: Bilirubin
  5. Serum haptoglobin
    • ↓ in intravascular haemolysis (its role is to mop up excess Hb)
‣
What condition does haemolysis predispose to?

Gout

  • Haemolysis → ↑ urate
‣
Hypothyroidism

See Endocrinology.

‣
Macrocytic anaemia
‣
Name 2 causes of megaloblastic macrocytic anaemia.
‣
B12 deficiency
‣
What are the causes?
  1. Malabsorption
    1. ↓ dietary intake
    2. Crohn's
    3. Coeliac
  2. Pernicious anaemia
    3. ‣
    What is the pathophysiology?
    • Autoimmune parietal cell destruction → ↓ intrinsic factor → ↓ B12 absorption
    ‣
    What do you test for?
    1. Intrinsic factor antibody
    2. Gastric parietal cell antibody
    ‣
    How do you manage this?
    1. Dietary IF replacement
    2. IM B12 injections, 3 monthly
‣
What will the neutrophils show?
  • Hypersegmentation
‣
Folate deficiency
‣
When treating folate deficiency, what is important to know & why?
  • B12 concentration
  • If B12 is low and you replace folate → Subacute combined degeneration of the cord
‣
Name 4 causes of non-megaloblastic macrocytic anaemia.
  1. Alcohol
  2. Liver dysfunction
  3. Pregnancy
  4. Reticulocytosis
‣
🩸 Clotting Cascade
‣
Basics
‣
What part of the coagulation cascade do APTT & PT represent?
  • Intrinsic pathway: APTT
  • Extrinsic: PT
‣
How is this pathway inhibited naturally?
  1. Tissue factor pathway inhibitor (TFPI): Forms complex with Xa which binds to VIIa:TF complex forming an inactive quaternary complex
  2. Anti-thrombin binds to Va/thrombin forming an inactive complex
    • Heparin acts through this channel
  3. Protein C/S: Protein S activates protein C → Protein C inactivates Va & VIIIa

Joe D, CC BY-SA 3.0
Joe D, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0/, via Wikimedia Commons. No changes were made.
‣
How do warfarin, DOACs and heparin work on the coagulation cascade?
  • Warfarin inhibits production of II, VII, IX, X
SteveKong3, CC BY-SA 4.0
SteveKong3, CC BY-SA 4.0 creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons. No changes were made.
‣
Bleeding
‣
Haemophilia
‣
Von Willebrand disease
‣
Presentation
‣
How is it inherited?
  • Autosomal dominant
‣
What does von Willebrand factor do?
  • Promotes platelet adhesion to damaged endothelium
  • Stabilises factor VIII → Deficiency leads to VIII inactivity
‣
What are the 3 types of vWD?
  1. Partial reduction (80%)
  2. Abnormal vWF
  3. Complete lack of vWF (autosomal recessive) → Very severe
‣
What are common symptoms? (3)

Platelet-pattern superficial bleeding:

  1. Easy bruising: Petechiae / purpurae
  2. Epistaxis
  3. Menorrhagia
‣
What is seen on a coagulation screen? (4)
  1. Normal PT
  2. Prolonged APTT
  3. Factor VIII decreased activity
  4. Prolonged bleeding time
‣
How is it managed?
  • Only managed if the patient has been symptomatic:
    • Tranexamic acid → Mild bleeding
    • Desmopressin → Stimulates vWF release
    • vWF & F.VIII infusion
‣
Haemophilia A/B
‣
What is deficient in haemophilia A & B, respectively?
  • A: Factor VIII
  • B: Factor IX
‣
Presentation
‣
How are they inherited?
  • X-linked recessive
‣
What is a common presentation?

Neonate/young child with severe large deep bleeds into soft tissue, joint & muscle:

  1. Haemarthrosis (bleeding into joints/muscles)
  2. Intracranial haemorrhage/haematoma
  3. Haematuria
‣
Investigations
‣
What is definitive for haemophilia A?
  • Serum factor VIII
‣
What would you see on a clotting screen?
  • ↑ APTT
  • ↔︎ Bleeding time
‣
How would you manage them?
  • Acutely for both: Tranexamic acid

Specifically:

  • Haemophilia A: Cryoprecipitate (Factor VIII, fibrinogen, von Willebrand factor and factor XIII)
  • Haemophilia B: IV infusion of factor IX (Replace the missing clotting factors)
‣
Platelets
‣
Thrombocytopenia

There are two main causes:

‣
Problems with production
  1. B12/folate deficiency
  2. Liver failure: ↓ Thrombopoietin
  3. Disorders affecting bone marrow production, e.g. leukaemia
‣
Problems with destruction
  1. Disseminated intravascular coagulopathy (DIC)
    2. ‣
    How does normal clot homeostasis work?
    • Coagulation cascade → Fibrin formation & polymerisation
    • Fibrin formation → Plasmin formation → Clot breakdown
    ‣
    What is the pathophysiology of DIC?
    • Large insult (e.g. sepsis) → Excessive TF release → Formation of hundreds of small clots using up all platelets
    ‣
    What are you looking for on FBC and clotting screen?
    • ↓ Platelets
    • ↑ APTT
    • ↑ PT
    • ↑ Bleeding time
  2. Immune thrombocytopenia (ITP)
    3. ‣
    What are the common causes of this?
    • Post-viral infection or vaccination
    ‣
    What features may they present with?
    • Petechiae
    • Bleeding (e.g. epistaxis)
    ‣
    How would you investigate it?
    • FBC: Isolated low platelets
    ‣
    How is it managed?
    • Conservative: Natural course 1-2 weeks
    • Platelet transfusion if severe bleeding
  3. Thrombotic thrombocytopenic purpura (TTP)
    4. ‣
    How do they present?
    1. Focal neurology
    2. Haemolysis (Microangiopathic → Schistocytes)
    3. Thrombocytopenia
  4. Haemolytic uraemic syndrome (HUS)
‣
Vitamin K deficiency
‣
When are you likely to get this?
  • Bile duct occlusion → ↓ fat emulsion → ↓ absorption of fat soluble vitamins ADEK
‣
Hereditary haemorrhagic telangiectasia
‣
What are the common presenting features?
  1. Red freckles on lips
  2. Recurrent epistaxis
  3. Other features: Brain, liver, lung bleeds
Michael Sand, Daniel Sand, Christina Thrandorf, Volker Paech, Peter Altmeyer, Falk G Bechara, CC BY 2.5
Michael Sand, Daniel Sand, Christina Thrandorf, Volker Paech, Peter Altmeyer, Falk G Bechara, CC BY 2.5 creativecommons.org/licenses/by/2.5, via Wikimedia Commons. No changes were made.
‣
How is it inherited?
  • Autosomal dominant
‣
What is the pathophysiology?

Arteriovenous malformations (AVMs)

  • Arteries flow directly into veins rather than capillaries → High pressure blood flow in veins → Vein tears and irritation → Bleeding
‣
Clotting
‣
Thrombophilia
‣
What is the simple pathophysiology of thrombophilia?
  • Defect in factors that normally inhibit the coagulation cascade → Excessive coagulation

Types:

  1. Antiphospholipid syndrome
    2. ‣
    What is this?
    • Persistent antiphospholipid antibodies associated with a variety of clinical features characterised by thromboses and pregnancy-related morbidity.
    ‣
    What are the risk factors?
    • History of systemic lupus erythematosus
    • History of other autoimmune rheumatological disorders
    • History of other autoimmune diseases
    • History of autoimmune haematological disorders
    ‣
    What antiphospholipid antibodies would we look for?
    1. Lupus anticoagulant
    2. Anticardiolipin antibody
    3. Anti-β2-glycoprotein I
    ‣
    How are they managed?

    Our main goals are management of acute thrombosis and prevention of thrombosis recurrence and pregnancy morbidity.

    1. LMWH initially before bridging to warfarin (or if pregnant remain on LMWH until after delivery)
    2. Lifelong warfarin:
      1. Target 2-3
      2. Target 3-4 (if VTE while on warfarin)
  2. Factor V Leiden (Most common hereditary)
    3. ‣
    What is Factor V Leiden?
    • Factor V is resistant to deactivation by protein C → Overly active factor V → Increased coagulation
  3. Protein C/S deficiency
    4. ‣
    Who is this common in?
    • Individuals from Southeast Asian heritage
    ‣
    How do proteins C & S work?
    • Protein C → Activated protein C → Breakdown of factor Va & VIIIa

    (via protein S)

  4. Antithrombin deficiency
‣
Deep vein thrombosis (DVT)
‣
How is the risk of DVT quantified?
  • Well's score for DVT (2-level)
    • ‣
    What scores are considered significant?
    • ≥ 2
    ‣
    If 'DVT likely' how is it investigated? (2)
    1. Proximal leg doppler within 4 hours
    2. D-dimer if negative
    ‣
    If 'DVT unlikely' how is it investigated? (3)
    1. D-dimer
    2. Positive: Doppler within 4 hours
      • If this isn't possible give LMWH
‣
How is DVT managed?
  • Initial: LMWH
    • Stop after 5 days or when the INR ≥ 2
    • If using a DOAC, no heparin bridging is needed.
  • Long-term: Warfarin/DOAC
    • Provoked: 3 months
    • Unprovoked: 6 months / lifelong
‣
What conditions need to be tested for in an unprovoked DVT?
  • Thrombophilia
  • Antiphospholipid antibodies
‣
👹 Cancer
‣
Leukaemia (White cells)
‣
General
‣
At what ages do the different leukaemia's present?

ALL CeLLmates have CoMmon AMbitions:

  1. ALL < 5 years / > 45 years
  2. CLL > 55 years
  3. CML > 65 years
  4. AML > 75 years
‣
Name 5 features likely on presentation of any patient with leukaemia.
  1. ↓ WCC (& neutropenic) → Infections
  2. ↓ Hb → Anaemia, lethargy, SOB
  3. ↓ Platelets → Bleeding
  4. Splenomegaly → Abdominal discomfort
  5. Bone pain
‣
What are your differentials for petechiae?
  1. Leukaemia
  2. Meningococcal septicaemia
  3. Vasculitis
  4. ITP
  5. HSP
  6. Non-accidental injury
‣
How does acute and chronic leukaemia differ in terms of cell type?
  • Acute: Blast cells
  • Chronic: Mature cells
‣
How are they managed?
  1. Chemotherapy
    • Risk of tumour lysis syndrome
  2. Steroids

Types:

‣
Acute lymphoblastic leukaemia (ALL)
‣
Who is it more common in?
  • Children - Accounts for 80% of childhood leukaemia - Good prognosis
    • Down's syndrome
  • Adults (> 45 years) - Poor prognosis
‣
What will the FBC look like?
  • High WCC
  • Lymphocytosis
‣
Chronic lymphocytic leukaemia (CLL)
‣
When is this commonly seen?
  • Adults (> 55y)
‣
Patient with known CLL has jaundice, LFT shows high unconjugated bilirubin. Diagnosis?
  • Warm AIHA
‣
What can this transform into? (What is the transformation called?)
  • High-grade lymphoma (Richter's transformation)
‣
What do you find on blood film?
  • Smudge cells - Represent fragile WBCs
‣
Acute myeloid leukaemia (AML)
‣
Who is it more common in?
  • > 75 years - Most common leukaemia in adults
‣
What is seen on blood film?
  • Auer rods
‣
What is APML?
  • Acute promyelotic leukaemia
  • Presents in ~ 30 y/o with AML & DIC features
‣
Chronic myeloid leukaemia (CML)
‣
What is the characteristic feature of this?
  • Philadelphia chromosome [t(9;22) Bcr-Abl translocation]
    • May have pseudo Pelger-Huet cells on blood film
  • Massive splenomegaly
‣
What are the 3 phases?
  1. Chronic (~ 5y): Often asymptomatic
  2. Accelerated: Blast cells take up 10-20% of blood
  3. Blast: > 30% of blast cells in blood → Pancytopenia & symptoms
‣
What can this develop in to?
  • Acute leukaemia - AML (80%)
‣
What is the first-line management?
  • Immunosuppression - Imatinib
‣
Lymphoma (B/T-cells)

Types:

‣
Hodgkin's lymphoma
‣
Feature
‣
When do they present?

Bimodal:

  1. ~ 20 years
  2. ~ 75 years
‣
What is the most common presentation?
  • Asymmetrical, painless lymphadenopathy
    • Can be painful when drinking alcohol
‣
What are the B symptoms? (4)
  1. Night sweats
  2. Fever
  3. Weight loss
  4. Prurius - itching
‣
What symptoms & signs signify a poor prognosis?
  1. B-symptoms
  2. Lymphocyte depletion
  3. Age > 45 years
  4. Male
  5. High WCC
‣
What are the RFs?
  • EBV
  • HIV
  • High socioeconomic class
  • Jewish ancestry
‣
What other features may be seen?
  • Normocytic anaemia of chronic disease
  • Eosinophilia
‣
What's the most common type?
  • Nodular sclerosing
‣
Investigations
‣
What blood test would you do?
  • LDH (non-specific)
‣
Name the 4 Ann-Arbor stages.

CT/MRI showing lymphadenopathy in:

  • Stage 1: 1 area
  • Stage 2: > 1 area, same side of diaphragm
  • Stage 3: > 1 area, opposite sides of diaphragm
  • Stage 4: Extra-nodal sites
‣
Interpret the following lymph node biopsy.
  • Reed-Sternberg cells (multiple nuclei) present in the centre
Ed Uthman, MD, CC BY-SA 2.0
Ed Uthman, MD, CC BY-SA 2.0 creativecommons.org/licenses/by-sa/2.0, via Wikimedia Commons. No changes were made.
‣
How are they managed?
  1. Chemotherapy
  2. Radiotherapy
‣
Non-Hodgkin's lymphoma
‣
How does the presentation of NHL differ from HL?
  • Lymphadenopathy is usually widespread
  • No Reed-Sternberg cells
  • More common in adults
‣
What are the poor prognostic markers? (4)
  1. Raised serum LDH
  2. B-symptoms
  3. Lymphadenopathy/organomegaly
  4. Anaemia

Types:

‣
Burkitt's
‣
What may you see on inspection?
  • Asymmetrical face swelling
Mike Blyth, CC BY-SA 2.5
Mike Blyth, CC BY-SA 2.5 creativecommons.org/licenses/by-sa/2.5, via Wikimedia Commons
‣
What infection is it assoicated with?
  • EBV
‣
What mutation is it associated with?
  • C-myc
‣
What is seen on microscopy?
  • 'Starry sky' appearance
‣
MALT
‣
What causes this?
  • H. pylori chronic stomach inflammation → Mucosa associated lymphoid tissue
‣
How is it managed?
  1. Triple therapy to eradicate H. pylori
‣
Diffuse large B-cell

Most common lymphoma in U.K.

‣
How does this present?
  • Rapidly growing painless mass in > 65y
‣
What infection is it associated with?
  • Hepatitis C
‣
Multiple myeloma (Plasma cells)
‣
How do these patients present?
  1. Calcium: Hypercalcaemia
  2. Renal failure: Antibodies block the tubule flow
  3. Anaemia: Bone marrow infiltration
  4. Bone pain/fractures: ↑ Osteoclast activity caused by cytokines released by plasma cells
  5. Bleeding: Thrombocytopenia
  6. Infection
‣
Investigations
‣
What are the initial diagnostic investigations?
  1. Urine Bence-Jones protein
  2. Serum-free Light-chain assay
  3. Serum Immunoglobulins
  4. Serum Protein electrophoresis
‣
What result will ALP & phosphate show?
  • Normal ALP (differentiates from bone metastases where ALP will be high)
  • Normal phosphate
‣
What is seen on blood film?
  • Rouleaux: Stacks of aggregated RBCs
‣
What is the best diagnostic investigation?
  • Bone marrow aspirate & biopsy: > 10% plasma cells in bone marrow
‣
What X-ray findings may you see?
  • Punched out lytic lesions
  • Raindrop skull
Mikael Häggström, CC0, via Wikimedia Commons
Mikael Häggström, CC0, via Wikimedia Commons
‣
How are pathological fractures prevented?
  • Bisphosphonates: Zolendronic acid
‣
How are they managed?
  1. Suitable for transplant: Allogenic/autologous HPSC transplant
  2. Not suitable: MPT → Melphalan, prednisolone, thalidomide
‣
Myeloproliferative disorders
‣
General
‣
What mutation is common in these patients?
  • JAK-2
‣
What is seen on bloods in each?
  • PV: Hb > 185/165
  • ET: Platelets > 600
‣
What can these develop into?
  • AML

Types:

‣
Primary myelofibrosis (Haematopoietic stem cells)
‣
What is the pathophysiology of this?
  • Cell line proliferation → Fibroblast stimulation → Bone marrow fibrosis → Pancytopenia
  • Haematopoiesis can happen in liver & spleen causing enlargement
‣
What is seen on bone marrow aspiration?
  • 'Dry tap' because the bone marrow is filled with fibrosed tissue
‣
What does the following blood film show?
  • Poikilocytosis (varying sizes)
  • Tear drop RBCs
Dr Graham Beards, CC BY-SA 3.0
Dr Graham Beards, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
Polycythaemia vera (Erythroid cell)
‣
Name 2 classic symptoms.
  1. Pruritus (intense)
  2. Joint pain: Gouty arthritis
‣
What are they predisposed to?
  • Clots: Hyperviscosity of blood
  • AML transformation
‣
What is first-line management?
  • Venesection
  • Aspirin
‣
Name the secondary causes of polycythaemia
  1. Dehydration: Pseudopolycythaemia (high RBC : plasma)
  2. COPD: ↓ SpO₂ → ↑ EPO → Polycythaemia
  3. Obstructive sleep apnoea
  4. Altitude
‣
Essential thrombocythaemia (Megakaryocyte)
‣
What is reactive thrombocytosis?
  • Platelets are an acute phase reactant so are raised in stress e.g. infection/surgery
‣
What is a characteristic symptom?
  • Burning sensation in the hands
‣
What malignancy is associated with thrombocytosis?
  • Lung
‣
🎞 Blood Films
‣
Name all of the blood film findings you may be looking for.
  1. Reticulocytes → Haemolytic anaemia
  2. Spherocytes → AIHA, hereditary spherocytosis
  3. Heinz bodies → G6PD, ɑ-thalassaemia
  4. Auer rods → AML
  5. Smudge cells → CLL
  6. Howell-Jolly bodies → Hyposplenism/splenectomy, severe anaemia
  7. Target cells → Fe deficiency anaemia / splenectomy
  8. Schistocytes (fragmented RBCs) → HUS, DIC, TTP, metallic valves
  9. Anisocytosis (variation in RBC size) → Myelodysplastic syndrome
  10. Sideroblasts (immature RBCs containing Fe blobs) → Myelodysplastic syndrome
‣
Visualising Cell Types
Ed Uthman, S Bhimji and Mikael Häggström, M.D. Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC BY 4.0
Ed Uthman, S Bhimji and Mikael Häggström, M.D. Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC BY 4.0 creativecommons.org/licenses/by/4.0, via Wikimedia Commons. No changes were made.

For the following blood films:

  1. Name the features seen on the film.
  2. Name the disease associated with these features.
Ed Uthman from Houston, TX, USA, CC BY 2.0
Ed Uthman from Houston, TX, USA, CC BY 2.0 creativecommons.org/licenses/by/2.0, via Wikimedia Commons. No changes were made.
‣
Film 1
  1. Target cells
  2. Thalassaemia/hyposplenism/sickle cell
Dr Graham Beards, CC BY-SA 3.0
Dr Graham Beards, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
Film 2
  1. 'Tear drop' poikilocytes (poik - oddly shaped RBCs)
  2. Myelofibrosis - Large megakaryocytes stimulate fibroblasts
Paulo Henrique Orlandi Mourao and Mikael Häggström, CC BY-SA 3.0
Paulo Henrique Orlandi Mourao and Mikael Häggström, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
Film 3
  1. Howell-Jolly bodies (remnants of the RBC nucleus, typically removed by the spleen)
  2. Hyposplenism
Prof. Osaro Erhabor, CC0, via Wikimedia Commons
Prof. Osaro Erhabor, CC0, via Wikimedia Commons
‣
Film 4
  1. Schistocytes
  2. Cold AIHA/mechanical heart valve/DIC (Any mechanical trauma)
S Bhimji, MD, CC BY 4.0
S Bhimji, MD, CC BY 4.0 creativecommons.org/licenses/by/4.0, via Wikimedia Commons. No changes were made.
‣
Film 5
  1. Acanthocytes
  2. Abetalipoproteinemia
‣
💊 Drugs
‣
Tumour lysis syndrome
‣
What cancers is it commonly related to?
  • High grade lymphoma
  • Leukaemia
‣
How is it usually triggered? Pathophysiology?
  • Combination chemotherapy
    • Chemotherapy → Tumour cell breakdown → Release of cell contents into blood stream
‣
What would signify this on blood tests?
  1. ↑ K⁺
  2. ↑ PO₄³⁻
  3. ↓ Ca²⁺
  4. ↑ Urea
‣
What do you need to have to confirm the diagnosis?
  • End organ damage:
    • ↑ serum creatinine
    • Cardiac arrhythmia
    • Seizure
‣
What prophylaxis would be given?
  • IV allopurinol
‣
What therapeutic drug should be given?

Treat each individual electrolyte abnormality:

  • IV rasburicase: Breaks down urea OR lactulose (longer acting)
  • Treat other electrolyte abnormalities as normal
‣
Tranexamic acid
‣
How does it work?
  • Binds to plasmin → Plasmin can't break down fibrin clot
‣
What is it most commonly used to treat?
  • Menorrhagia
‣
Where else is it used?
  • Trauma: IV bolus slowly infused
‣
What drugs can cause aplastic anaemia?
  1. Phenytoin
  2. Chloramphenicol
  3. Carbamazepine
  4. Quinine
‣
Blood products
‣
Blood transfusion
‣
What complications can occur?
  1. Immunological:
    • Acute haemolytic
    • Non-haemolytic febrile
    • Allergic/anaphylaxis
  2. Infective
  3. Transfusion-related acute lung injury (TRALI)
  4. Transfusion-associated circulatory overload (TACO)
  5. Other: Hyperkalaemia, iron overload, clotting
‣
How fast is a blood transfusion given in a non-urgent and urgent scenario?
  • Urgent (major haemoorhage): STAT
  • Non-urgent: 90 mins – 2 hours
‣
When do you transfuse platelets in patients with acute haemorrhage and not acutely unwell patients, respectively?
  • Haemorrhage < 100 x 10⁹
  • Not unwell < 30 x 10⁹
‣
What is used for emergency reversal of anticoagulation?
  • Prothrombin complex concentrate
‣
What is used in a 'clinically significant' haemorrhage in patients with an INR > 1.5?
  • Fresh frozen plasma
‣
What is given to replace fibrinogen?
  • Cryoprecipitate

🥴 Endocrinology

‣
🧠 Pituitary
‣
Prolactin
‣
Name features of excess prolactin in both men and women.
  • Men: Galactorrhoea, impotence, loss of libido
  • Women: Galactorrhoea, amenorrhoea
‣
What neurotransmitter inhibits prolactin release?
  • Dopamine
‣
Name 5 causes of raised prolactin
  1. Prolactinoma
  2. Pregnancy
  3. Oestrogens
  4. Physiological: Stress, exercise, sleep
  5. Acromegaly (1/3 of patients)
‣
Name 3 drugs that cause raised prolactin.

Think dopamine antagonists:

  1. Fluoxetine
  2. Metoclopramide
  3. Haloperidol
‣
How are they managed?
  1. Dopamine agonist: Bromocriptine/cabergoline
  2. Trans-sphenoidal hypophysectomy
‣
Growth Hormone
‣
What are the causes of acromegaly?
  1. Pituitary adenoma (95%)
  2. Ectopic production of GHRH - SCLC or pancreatic cancer
‣
Name the common features.
  • Facial: Coarse features, prognathism (gurn), macroglossia, frontal bossing
  • Body: Wedding ring no longer fits spade-like hands, increase in shoe size
  • Pituitary: Bitemporal hemianopia, headache, hypopituitarism
‣
Why may they get galactorrhoea?
  • 1/3 of patients with acromegaly have hyperprolactinaemia
‣
Name 3 investigations you may want to do.
  1. Serum IGF-1: High
  2. Oral glucose tolerance test (OGTT): GH won't be suppressed
    • High glucose normally suppresses GH
  3. MRI brain: Pituitary
‣
Name 3 complications.
  1. Cardiomyopathy (hypertrophic)
  2. Hypertension
  3. T2DM (> 10%)
  4. Colorectal cancer
‣
How are the majority of cases managed?
  • Trans-sphenoidal surgical removal
‣
What medical treatment may be used, and when?
  1. Somatostatin analogue (Octreotide): Directly inhibits GH release
  2. Bromocriptine: Dopamine agonist
‣
ADH
‣
When is ADH released & how does it work?
  • Released when the plasma osmolality is high
  • Inserts aquaporins into the collecting ducts to retain water resulting in lowering the plasma osmolality
‣
SIADH
‣
What is the problem with ADH here?
  • Overproduction
‣
Name 5 causes of SIADH.
  1. Pituitary overpoduction
  2. Small cell lung cancer
  3. Infection - Atypical pneumonia / lung abscess
  4. Head injury
  5. Medications: Thiazide diuretics, carbamazepine, SSRIs, NSAIDs
‣
How would they present?
  • Euvolaemic
  • Headache, fatigue
  • Muscle aches & cramps
  • Confusion
‣
What would you see on U&E?
  • ↓ Na
‣
What could be other causes of this & how would you rule them out?
  • Addison's - Synacthen test
  • Diuretics - MH
  • D&V - History
  • CKD/AKI - Visible on U&E
‣
Management:
‣
What is the definitive treatment?
  • Establish & treat underlying cause
‣
When correcting the sodium what is important to remember?
  • Correct slowly to prevent central pontine myelinolysis (< 10mmol/L per 24h)
‣
How is the sodium corrected?
  1. Fluid restriction
  2. Tolvaptan (ADH receptor blocker) - Cause rapid increase in Na
‣
Diabetes Insipidus
‣
What is the problem with ADH here?
  • Either not produced or not responded to
‣
What symptoms will this individual be experiencing?
  • Polyuria
  • Polydipsia
‣
What are the two types and their common causes?
  1. Cranial
    • Trans-sphenoidal pituitary surgery, head injury
  2. Nephrogenic
    • Lithium therapy
‣
Investigations:
‣
What would be your intitial investigations in primary care?
  1. Bloods: FBC, U&E (↑ Na)
  2. Fasting glucose: Consider DM
  3. Urine & serum osmolality
    • In DI: ↑ serum osmolality, ↓ urine osmolality
‣
What is the diagnostic test for DI?
  • Water deprivation test: Urine osmolality should increase as patient gets dehydrated. If it doesn’t → DI.
‣
What test differentiates between the two types?
  • Desmopressin stimulation test:
    • Cranial: Urine osmolality will increase (more concentrated) - they respond to ADH
    • Nephrogenic: No response
‣
What is the treatment for each type, respectively.
  • Cranial: Vasopressin/desmopressin
  • Nephrogenic: Chlorothiazide diuretic
‣
🥺 Thyroid
‣
Name 10 causes of a goitre.
  • Smooth:
    1. Graves' disease
    2. Hashimoto's thyroiditis
    3. De Quervain's thyroiditis
    4. Iodine deficiency/excess
    5. Drugs: Lithium / amiodarone
    6. Infiltration (sarcoidosis, haemochromatosis)
  • Nodular:
    1. Toxic multinodular goitre
    2. Solitary thyroid nodule (toxic/non-functional)
    3. Cancer
    4. Thyroglossal cyst
‣
Hyperthyroidism
‣
A patient has hyperthyroidism, name the 4 potential thyroid pathologies causing this.
  1. Graves disease: Non-tender goitre
  2. Toxic multinodular goitre
  3. Solitary toxic thyroid nodule
  4. De Quervain's thyroiditis (in subacute hyperthyroid phase of disease): Tender goitre.
‣
Definitions:
‣
What is hyperthyroidism?
  • Over-production of thyroid hormone by the thyroid gland
‣
What is thyrotoxicosis?
  • Excessive quantity of thyroid hormone in the body
‣
What is Graves' disease?
  • An autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism
‣
What is a toxic multinodular goitre?
  • Nodules develop on the thyroid gland that act independently of the normal feedback system and continuously produce excessive thyroid hormone.
‣
What is a thyroid storm?
  • Severe presentation of hyperthyroidism with pyrexia, tachycardia & delirium
    • ‣
    What events may precipitate it?
    • Infection, thyroid surgery, trauma
‣
Signs & symptoms:
‣
Name symptoms of thyrotoxicosis.
  1. Sweating & heat intolerance
  2. WL
  3. Fatigue
  4. Anxiety & irritability / restlessness
‣
Name 4 signs associated with all hyperthyroidism cases.
  1. Tachycardia
  2. Tremor
  3. Palmar erythema
  4. Lid lag & retraction
  5. Diffuse goitre
‣
Name 4 signs present in Graves, but not all hyperthyroid cases.
  1. Thyroid acropachy
  2. Exophthalmos - TSH antibodies cause eye muscle inflammation, swelling & hypertrophy
  3. Ophthalmoplegia
  4. Pretibial myxoedema
‣
How do you investigate a patient with thyrotoxicosis?
  • TFTs
  • TSH receptor stimulating antibody - Graves
  • Anti-TPO antibody - Graves
  • USS +/- biopsy - Tumour
‣
What are the 3 options for managing thyrotoxicosis?
  1. Carbimazole
    2. ‣
    How does it work?
    • Stops I₂ from being converted to I⁻ reducing thyroid hormone formation.
    ‣
    Complications?
    • Agranulocytosis
    • Teratogenic
  2. Propylthiouracil
    3. ‣
    How does it work?
    • Similar mechanism to carbimazole
    • Stops I₂ from being converted to I⁻ reducing thyroid hormone formation.
    ‣
    When is it first-line?
    • Pregnancy & thyroid storm
    ‣
    Complication?
    • Risk of severe hepatic reaction → Death
  3. Radioiodine (Lugol's iodine)
    4. ‣
    How does it work?
    • Taken up by thyroid cells and the radiation kills them
    ‣
    When is it contraindicated?
    • Pregnancy
    • Age < 16y
    • Thyroid eye disease (worsens it)
    ‣
    Key side effect?
    • Hypothyroidism
‣
Name all of the drugs used in a thyroid storm.
  1. Propylthiouracil
  2. Beta blocker (IV propranolol) - Tachycardia
  3. Antiarrhythmics
  4. Prednisolone - Reduces conversion of T4 to T3
‣
Hypothyroidism
‣
Name the characteristic features.
  • Weight gain, lethargy
  • Dry skin, coarse hair, loss of lateral eyebrow
  • Menorrhagia
  • Constipation
  • May have amenorrhoea because TRH stimulates prolactin release
‣
Management
‣
What are the standard doses of levothyroxine?
  • 50-100 micrograms
‣
How do you monitor if levothyroxine treatment is effective?
  • Serum TSH (keep in normal range)
‣
How do you need to change levothyroxine management in pregnancy?
  • Increase it by 25-50 micrograms
‣
What are the SEs?
  • Hyperthyroidism
  • Reduced bone mineral density
  • Can worsen angina
  • Atrial fibrillation
‣
What does levothyroxine interact with?
  • Iron (reduces absorption), give them 2 hours apart
‣
Myxoedemic coma
‣
What is this?

Severe hypothyroidism leading to low everything: Consciousness, HR, BP, temperature.

  1. Confusion
  2. Bradycardia
  3. Hypotension
  4. Hypothermia
‣
How is it managed?
  1. IV levothyroxine
  2. IV hydrocortisone: Assume that the low thyroid has lead to adrenal insufficiency

Cases:

‣
A woman presents with weight gain, lethargy and menorrhagia, a goitre and anti-TPO antibodies are found, what does she have?
  • Hashimoto's thyroiditis
    • Non-tender goitre
‣
A man who had a cough 3 weeks ago presents with tachycardia and tremor. His symptoms then settle, but 6 weeks later he presents with weight gain and lethargy. What does he have?
  • De Quervain's (subacute) thyroiditis
    • Tender goitre
‣
A patient from Africa who has recently moved to the UK is found to have hypothyroidism on TFT. What is the most likely cause?
  • Dietary iodine deficiency
‣
A patient with bipolar disorder has hypothyroidism. What is the likely cause?
  • Lithium therapy (can also cause a goitre)
  • Amiodarone also causes hypothyridism
‣
TFTs
TSH
Free T4
Diagnosis (See answers below)
↓
↑
A
↑
↓
B
↓
↓
C
↑
↔︎
D
↓
↔︎
E

Answers:

‣
Diagnosis A
  • Primary hyperthyroidism
‣
Diagnosis B
  • Primary hypothyroidism
‣
Diagnosis C
  • Secondary hypothyroidism / sick euthyroid syndrome
‣
Diagnosis D
  • Subclinical hypothyroidism / poor compliance with thyroxine
‣
Diagnosis E
  • Steroid therapy
‣
Thyroid cancer
‣
Do thyroid cancers commonly secrete hormones?
  • No - very rare
‣
What are the two most common thyroid malignancies?
  1. Papillary (70%) - Often young females (good prognosis)
    2. ‣
    What histological sign is diagnostic of this?
    • Orphan Annie cells
  2. Follicular (20%)
‣
A patient presents with a solitary thyroid nodule, what is this likely to be?
  • Follicular adenoma - test to see if it's malignant
‣
A patient presents with MEN-2, what thyroid malignancy are they likely to have?
  • Medullary - Parafollicular
‣
Patient presents with hypocalcaemia and raised serum calcitonin, what malignancy is this?
  • Medullary
  • Malignant C-cells (parafollicular)
‣
How are they usually managed?
  • Total thyroidectomy
  • Followed by radioiodine to mop up residual cells
  • Levothyroxine replacement
‣
🦴 Parathyroid
‣
How does PTH work?

↓ serum Ca²⁺ causes:

  1. PTH release from parathyroid glands stimulating:
    1. ↑ osteoclast activity → ↑ Ca²⁺ absorption from bone
    2. ↑ kidney reabsorption of Ca²⁺
  2. ↑ 1-ɑ-hydroxylase release in the kidney → ↑ calcitritol (active vitamin D) → ↑ intestinal absorption of Ca²⁺
‣
Hormone profile cases:
Calcium
Phosphate
PTH
ALP
Diagnosis
↓/↔︎
↑
↑
↑/↔︎
A
↑
↓
↑
↑
B
↑
↓/↔︎
↑
↑
C
↑
↑
↓
↑
D
↓
↑
↑
↔︎
E
‣
Diagnosis A
  • Secondary hyperparathyroidism (e.g. vitamin D deficiency, CKD)
‣
Diagnosis B
  • Primary hyperparathyroidism
‣
Diagnosis C
  • Tertiary hyperparathyroidism
‣
Diagnosis D
  • Malignancy (non-parathyroid)
‣
Diagnosis E
  • Pseudohyperparathyroidism
‣
Presentation:
‣
What are the features of hypercalcaemia?
  • Bones - Oesteopenia/porosis
  • Stones - Kidney stones
  • Psychic moans - Confusion, depression
  • Abdominal groans - Pancreatitis, constipation
‣
A patient with CKD presents with low calcium and high PTH, what type is this and how is it managed?
  • Secondary
    • Low 1-ɑ-hydroxylase → Low active vitamin D → ↓ Ca2+ → ↑ PTH
  • Vitamin D analogues
‣
This patient is treated, but their PTH continues to be high, what is this and how is it managed?
  • Tertiary: Parathyroid hyperplasia has occurred over time
  • Surgical resection
‣
An elderly female presents with an unquenchable thirst and a raised PTH level. What is it likely to be and what is the management?
  • Primary - Solitary adenoma
  • Total parathyroidectomy
‣
What is a characteristic feature seen on XR?
  • Pepperpot skull
  • Reduced bone mineral density/erosion
‣
What other neoplasias is it associated with?
  • MEN disorders
‣
🍰 Diabetes
‣
What test can differentiate the 2 types?
  • C-peptide: Precursor is broken down into insulin & C-peptide, therefore in T1DM it will be low, in T2DM it will be high

Types:

‣
Type 1 diabetes mellitus
‣
DKA
‣
Name the 3 ketone bodies.
  • Acetone
  • Acetoacetate
  • β-hydroxybutyrate
‣
Name 3 precipitating factors.
  • Infection
  • Missed insulin
  • MI
‣
Name 5 symptoms.
  • Abdominal pain
  • Polyuria
  • Polydipsia
  • Kussmaul's respiration - trying to breathe out CO2 due to acidosis
  • Pear drop breath
‣
What do you need for diagnosis
  1. Acidosis: pH < 7.3 or plasma bicarbonate below 15mmol/litre.
  2. Ketonaemia: Ketones (beta-hydroxybutyrate) > 3 mmol/litre.
  3. Blood glucose is generally high (> 11mmol/litre), but children can develop DKA with normal glucose.
‣
Management:
‣
What is the immediate initial management?
  • IV fluids → NaCl 500mL 0.9%
‣
What needs to be given next & dose?
  • Fixed rate insulin infusion → 0.1 unit/kg/hr (80kg = 8 units/hr)
    • Continue long-acting insulin, stop short acting
‣
What needs to be monitored and corrected throughout treatment and how is this done?
  • Potassium: Risk of hypokalaemia
    • K⁺ 3.5-5.5 → Add 40mg KCl into IV fluids
  • Sodium: Risk of cerebral oedema if going from aggressive fluid resuscitation
‣
Hypoglycaemia
‣
What are the symptoms?
  • Blurred vision
  • Weakness
  • Recurrent headaches
‣
Name 6 causes of this. (EXPLAIN)
  • EXogenous drugs - insulin, sulphonylureas
  • Pituitary dysfunction
  • Liver failure
  • Addison's disease
  • Insulinoma
  • Non-pancreatic neoplasms
‣
How do you differentiate exogenous insulin intake from endogenous production (insulinoma)?
  • Serum C-peptide → High in endogenous production as it's a by-product of the synthesis
    • Give insulin: Normally C-peptide will fall, in insulinoma it will remain the same
‣
How is it managed in hospital & GP, respectively?
  1. Conscious (both): Lucozade drink
  2. Unconscious:
    • Hospital: 200ml 10% IV dextrose
    • GP: IM glucagon
‣
Insulin therapy
‣
What is insulin sliding scale & when is it used?
  • Two separate infusions, one of glucose and one of insulin
  • Rates can be easily adjusted based on BM results so used in medical management of diabetic inpatients
‣
Who doesn't need to inform the DVLA if on insulin?
  • Temporary treatment for ≤ 3 months or less
  • GDM that are taking insulin for < 3 months post-delivery

Give an example of each of the following:

‣
Rapid-acting
  • Novorapid
‣
Short-acting
  • Actrapid
‣
Intermediate-acting
  • Isophane
‣
Long-acting
  • Levemir / Lantus
‣
Type 2 diabetes mellitus
‣
Diagnosis:
‣
How does diagnosis differ between a symptomatic and asymptomatic patient?
  • Symptomatic - 1 HbA1c, fasting BM or random BM reading needed
  • Asymptomatic - 2 HbA1c readings needed
‣
What HbA1c represents pre-diabetes and diabetes?
  • 42-47 - Pre-diabetes
  • ≥ 48 - Diabetes
‣
What do fasting and random BM readings need to be for diabetes?
  • Fasting
    • 6.1-7 → Impaired fasting glucose
    • ≥ 7 → Diabetes
  • 2h glucose
    • ≥ 7.8 → Impaired glucose tolerance
    • ≥ 11 → Diabetes
  • Random
    • ≥ 11 → Diabetes
‣
In what patients can HbA1c not be used?
  • Increased RBC lifespan - Hb higher than reality
    • Anaemia
      • Fe-deficiency
      • Vitamin B12/folate deficiency
    • Splenectomy
  • Decreased RBC lifespan - Hb lower than reality
    • Sickle cell anaemia
    • G6PD deficiency
    • Hereditary spherocytosis
  • Other
    • CKD
    • Children
    • HIV
    • Gestational diabetes (not enough time)
‣
BP targets:
‣
When is it < 140/80?
  • Diabetes without end-organ damage
‣
When is it < 130/80?
  • Diabetes with end-organ damage
‣
Management targets:
‣
Between what HbA1c values should lifestyle and metformin titration be primarily used?
  • 48-58
‣
At what HbA1c value should a second drug be added?
  • ≥ 58
‣
What are the HbA1c targets for metformin management and sulphonylurea management, respectively?
  • Metformin: 48
  • Sulphonylurea: 53
‣
Is there a preferred second-agent in management?
  • No. Any are acceptable.
‣
Drugs:
‣
What is the incretin effect? What 2 drugs enhance this effect?
  • Give PO and IV glucose and more insulin will be produced from PO because intestines secrete GLP-1
    • GLP-1 agonists (Exenatide) - mimic GLP-1
    • DPP-4 inhibitors - Prevent the breakdown of GLP-1 therefore increasing its effect
‣
What insulin regime should they be started on in severe DM?
  • Basal therapy - Isophane insulin. Add a bolus after meals if BM is very high

The following are examples of which classes, and name the common SEs & CIs of each:

‣
Canagliflozin
  • SGLT-2 inhibitor
  • Stops reabsorption of glucose back into blood in the PCT
  • SE: UTI
  • Relies on decent kidney function
‣
Exenatide (Give indications & target)
  • GLP-1 agonist
  • I: BMI ≥ 35 OR BMI < 35 but can't have insulin for occupation
  • T: Drop in HbA1c of 11 & 3% WL over 6 months
  • SE: Pancreatitis
‣
Sitagliptin
  • DPP-4 inhibitor
  • Doesn't cause weight gain so use in very overweight
  • SE: Pancreatitis
‣
Pioglitazone
  • Thiazolidenedione
  • Increases peripheral insulin sensitivity
  • SE: Weight gain, fluid retention, osteoporosis, liver dysfunction
  • CI: Heart failure
‣
Hyperglycaemic Hyperosmolar Syndrome (HHS):
‣
Over what time period does HHS come on?
  • Days - therefore the dehydration & electrolyte abnormalities are very bad
‣
What is the pathophysiology?
  1. Hyperglycaemia → Osmotic diuresis → Electrolyte losses
  2. Dehydration → Hyperviscosity of blood → Vascular complications
  3. Hypertonicity (constriction) of blood vessels compensates so they don't look as ill as they actually are
‣
What factors are used in diagnosis?
  • Hyperglycaemia: usually > 30 (no ketones/acidosis)
  • BP: Hypotension
  • Raised serum osmolality
‣
What are the 3 key management steps for HHS?
  1. IV fluids: Dilutes hyperglycaemia and increases blood volume
  2. Correct electrolytes
  3. Normalise glucose: Usually don't use insulin as it will drop glucose too quickly and cause significant volume depletion. Fluids usually does the job

Complications:

‣
Diabetic neuropathy
‣
What drugs are used for management of diabetic peripheral neuropathy?
  1. Amitryptiline
  2. Duloxetine
  3. Gabapentin
  4. Pregabalin
‣
A patient with poorly controlled diabetes presents with bloating and vomiting and a very high BM. What has occured here and how is it managed?
  • Gastric neuropathy → Gastroparesis
  • Metoclopramide (prokinetic)
‣
Diabetic retinopathy
‣
Non-proliferative
  • Mild: ≥ 1 microaneurysm
  • Moderate:
    • Blot haemorrhage
    • Hard exudates (lipid leakage exudate)
    • Cotton wool spots (damage to nerve fibres → white patches)
  • Severe: Microaneurysms in all 4 quadrants, bleeding in ≥ 2 quadrants
Renátó BesencziJános TóthAndrás Hajdu, CC BY-SA 4.0
Renátó BesencziJános TóthAndrás Hajdu, CC BY-SA 4.0 creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons. No changes were made.
‣
Proliferative

Abnormal new blood vessels that grow on the surface of the retina.

  • Treatment: Anti–vascular endothelial growth factor therapy (Anti-VEGF).
‣
👹 Adrenals
‣
Cushing's syndrome
‣
General:
‣
Draw the glucocorticoid negative feedback loop.
OpenStax College, CC BY 3.0
‣
What are the two broad causes of Cushing's and which is more common?
  • Exogenous (more common) - steroids
  • Endogenous
‣
Name 4 causes of Cushing's.
  1. Pituitary tumour (most common endo cause)
  2. Adrenal adenoma
  3. SCLC - secretes ACTH
  4. Exogenous steroid use
‣
Name the common features of Cushing's.
  • Striae
  • Weight gain
  • Easy bruising
  • Diabetes
  • Interscapular fat pad
  • Spinal tenderness
  • Hypertension
‣
What is pseudo-Cushing's and how do you differentiate it from Cushing's?
  • Mimics the features of Cushing's but due to excess alcohol intake
  • Insulin stress test → Impaired glucose tolerance in Cushing's but not in pseudo
‣
Investigating:
‣
What test would you do for this in GP?
  • 24 hour urinary cortisol
‣
What electrolyte abnormality may be seen?
  • Hypokalaemic metabolic alkalosis
    • Hypokalaemia → Cortisol stimulates aldosterone receptor
    • Alkalosis → K in tubule is swapped for H
‣
How does the Dexamethasone suppression test work?
  • Give exogenous steroid → Normal response is for ACTH and cortisol to drop due to negative feedback. This doesn't occur in Cushing's syndrome.
  • Low-dose is given first to rule out exogenous use, followed by high-dose to localise the Cushing’s syndrome pathology.

Dexamethasone Suppression Test Results

Dose
Serum Cortisol
ACTH
Result
Low (1mg)
↓
A
↑/↔︎
B
High (8mg)
↓
C
↑/↔︎
↓
D
↑/↔︎
↑
E
‣
Result A
  • Normal response - could be exogenous steroid intake
‣
Result B
  • Cushing's syndrome - Cortisol release is not suppressed
‣
Result C
  • Cushing's disease - Pituitary is suppressed by high dose.
‣
Result D
  • Adrenal Cushing's - Negative feedback from dexamethasone stops pituitary secretion of ACTH, therefore it’s low.
‣
Result E
  • Ectopic ACTH production (e.g. SCLC) - Dexamethasone doesn’t suppress production because cells are malignant.
‣
How is it managed in most cases?
  • Surgical removal of the adenoma/tumour that is causing the problem
  • Medical management until surgery: Metyrapone (blocks steroid synthesis pathway)
‣
Addison's disease
‣
Causes & features:
‣
Name 4 primary causes of hypoadrenalism.
  1. Autoimmune (80%)
  2. Tuberculosis
  3. Metastases to adrenals (e.g. bronchial)
  4. Waterhouse-Friderichsen syndrome
    5. ‣
    What is this?
    • Adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection, e.g. meningococcal septicaemia.
‣
Name 2 secondary causes.
  1. Pituitary dysfunction: Surgery, infection, Sheehan's syndrome
  2. Congenital pituitary hypoplasia
‣
Name 1 tertiary cause.
  • Exogenous steroid intake (for > 3 weeks) → Hypothalamic suppression of CRH
‣
Name the common features of Addison's.
  • Lethargy
  • Weakness
  • N&V
  • Hyperpigmentation (palm & buccal): Excess ACTH is converted to ɑ-MSH
‣
Investigations:
‣
What electrolyte abnormalities may be seen?
  • Hyperkalaemia
  • Hyponatraemia
  • Metabolic acidosis
  • Hypoglycaemia
‣
What else would you like to test for?
  • BM - Hypoglycaemia
‣
How would you test for this in general practice?
  • 9AM serum cortisol (ACTH, aldosterone & renin)
‣
What is the definitive investigation, and what do they results represent?
  • Synacthen test (synthetic ACTH)
    • Low cortisol - Primary
    • High cortisol - Secondary
‣
Management:
‣
Name 2 medications given to treat this.
  • Hydrocortisone - Glucocorticoid
  • Fludrocortisone - Mineralocorticoid
‣
If the patient has an infection, should treatment change?
  • Yes - Double the glucocorticoid dose
‣
A patient with RA presents for an elective cholecystectomy, after the surgery she is hypotensive and very unwell. What has occurred here and how is it managed?
  • Addisonian crisis - the trauma needed to be accommodated for with additional glucocortocoid.
  • 100mg IV hydrocortisone, repeat 6 hourly (see local guidelines).
    • Fludrocortisone is not needed due to hydrocortisone having enough effects on its receptors in an acute situation.
  • IV fluids (dextrose if hypoglycaemic)
‣
Primary hyperaldosteronism (Conn’s syndrome)
‣
Name the 2 main causes.
  1. Bilateral adrenal hyperplasia (BAH) - 70%
  2. Adenoma (Conn’s) - 30%
‣
Name the 3 main features.
  1. Hypertension
  2. Hypokalaemia
  3. Alkalosis
‣
What result would be seen on an aldosterone : renin ratio?
  • High aldosterone, low renin (negative feedback)
‣
Why do a CT/adrenal vein sampling?
  • Decide whether it’s Conn's or BAH - is it unilateral?
‣
How does management differ between the 2 types?
  • Conn's - Surgical removal
  • Bilateral adrenal hyperplasia - Spironolactone
‣
Pheochromocytoma
‣
What is this a tumour of?
  • Chromaffin cells of the adrenal medulla
‣
When may you consider this as being a cause of HTN?
  • Treatment resistant HTN
‣
Name 3 investigations you may carry out.
  1. Urinary metanephrines (VMA)
  2. Serum metanephrines - High sens & spec
  3. CT/MRI abdomen - Locate lesion
‣
What are the first and second stages in the management?
  1. Acute:
    1. IV phentolamine (ɑ-blocker): Short acting
    2. Phenoxybenzamine (ɑ-blocker): Longer acting
    3. Labetalol: After ɑ-blockade
  2. Adrenalectomy (4-6 weeks after)
‣
🤔 Other
‣
Multiple endocrine neoplasia (MEN)

What neoplasias make up the following conditions?

‣
MEN 1
  • Pituitary
  • Parathyroid
  • Pancreas - Insulinoma (hypoglycaemia following exercise/fasting), gastrinoma
‣
MEN 2A
  • Parathyroid
  • Pheochromocytoma
  • Medullary thyroid (C-cells)
‣
MEN 2B
  • Medullary thyroid (C-cells)
  • Pheochromocytoma
  • Marfanoid habitus
  • Neuromas
‣
Stress response
‣
What are the main hormones raised?
  • Cortisol
  • Aldosterone
  • Adrenaline
  • GH
  • Glucagon
‣
What hormones are suppressed?
  • Insulin - need more glucose in stress situations
  • Testosterone
  • Oestrogen
‣
What hormones don't change?
  • TSH
  • FSH & LH
‣
What drug class suppresses hypothalamic and pituitary hormone secretion?
  • Opioids
‣
Obesity: Medications
‣
What is orlistat?
  • Pancreatic lipase inhibitor causing reduction in appetite
‣
What are the indications for its administration?
  • BMI ≥ 28 & associated RFs
  • BMI ≥ 30
  • Need to show sustained WL and not usually used for > 1 year

🤘🏼 Rheumatology

‣
🦴 Bone
‣
Joint disease
‣
Arthritis
‣
Hip Pain in Adults - Name the condition.
‣
65 year old obese patient presents with joint pain that is is worse when exercising and relieved by rest. What is it?
  • Osteoarthritis
‣
Patient presents with burning sensation over the antero-lateral thigh. What is this and what causes it?
  • Meralgia paraesthetica
  • Compression of lateral cutaneous nerve (trauma, obesity, tight clothing)
‣
Patient presents with hip pain. O/E: Hip extended with a straight leg and as the knee is bent there is severe pain. What is this?
  • Referred lumbar spinal pain to the hip
  • Trapped femoral nerve (L3/4)
‣
70 year old female patient presents with pain & tenderness over the lateral thigh. What is this likely to be?
  • Greater trochanteric pain syndrome (Trochanteric bursitis)
  • Repeated IT band movement
‣
Pregnant lady presents with pain over the pubic region that radiates into the groins and medial thigh. You notice a waddling gait. What is this?
  • Pubic symphysis dysfunction
‣
Patient presents with hand pain worse in the morning that improves when moving it, and also has abnormal nodules on the skin and SOB.
  • Inflammatory arthritis - RA
‣
Rheumatoid arthritis
‣
What are the key features seen in RA? (4)
  1. Symmetrical distribution - bilateral
  2. Swollen, painful joints in hands & feet
    3. ‣
    What joints are commonly affected?
    • PIP (DIP never affected in RA - think Heberden's in OA/psoriatic)
    • MCP
    • Wrist & ankle
  3. Worse in the morning, improves with movement
  4. Systemic involvement
‣
Name the following deformities:
‣
Answer
  • Top: Swan neck - Snapped extensor tendon
  • Bottom: Boutonnieré - Snapped flexor tendon
image
image
‣
Investigations:
‣
What bloods are needed to investigate? (6)
  • FBC, U&E, LFT, CRP, ESR
  • Rheumatoid factor (+ in 60-70%)
  • Anti-CCP antibodies (+ in 70%)
‣
What are the key features on X-Ray? (5)
  1. Loss of joint space
  2. Juxta-articular osteoporosis
  3. Soft-tissue swelling
  4. Periarticular erosions (late) - dark areas
  5. Subluxation - dislocation (late)
image
‣
What other investigation is useful & why?
  • Joint USS to evaluate synovitis
‣
What is seen on joint aspiration?
  • ↑ WCC (predominantly neutrophils)
  • Yellow & cloudy, no crystals
‣
What is the first-line therapy? (4)
  1. DMARD - Methotrexate (7.5 mg OW)
    • Folate supplementation
  2. Steroids - Prednisolone (1-10mg PO OD)
    • IM methylprednisolone is another option for acute flare
    • Low dose is required apart from if they develop eye involvement or vasculitis, then higher doses may be needed
    • PPI - Prevent GI bleed
‣
How is the response to treatment monitored? (3)
  • Disease activity scoring - DAS28 (Assesses 28 joints)
    • Points for: Swelling, tenderness & ESR/CRP result
  • FBC & LFT monitoring if on DMARD (4-8W at start then 3-4M)
    • FBC - Hb (anaemia), WCC
    • LFT - ALT/AST
‣
What other options are there for treatment resistant RA?
  • Second-line: Add sulfasalazine/leflunomide
  • Third: Methotrexate + Infliximab, adalimumab, etanercept (anti-TNF)
  • Fourth: Methotrexate + Rituximab (anti-CD20)
    • Destroys B-cells
‣
Name 5 complications of RA.
  1. Eyes - Sjogren's (sicca syndrome)
  2. Atlantoaxial subluxation
    3. ‣
    When do you need to consider this?
    • Any surgery under GA - Requires neck movement
    ‣
    How do you investigate for this?
    • Anteroposterior and lateral cervical spine radiographs
image
‣
Patient with RA presents with splenomegaly and neutropenia. What is this?
  • Felty's syndrome (SANTA)
image
‣
Osteoarthritis
‣
How does OA develop?

Wear & tear → Loss of articular cartilage → Bone remodelling → Inflammatory changes

‣
What is a typical presentation? What joints are affected? (4)
  • Elderly individual presents with unilateral joint pain in a large, weight bearing joint
  • Joints:
    • Fingers - DIP (Heberden's node), PIP (Bouchard's nodes), carpometacarpal
    • Knee
    • Hip
      • image
‣
Name 4 X-Ray changes.
  1. Loss of joint space
  2. Subchondral sclerosis
  3. Subchondral cysts
  4. Osteophytes
image
‣
What are the 3 conservative management steps?
  1. Paracetamol & topical NSAIDs
  2. Oral NSAIDs + PPI / Opioids
  3. Intra-articular steroids
‣
Seronegative arthropathy
‣
Ankylosing spondylitis
‣
Diagram: The pathophysiological process
Senseiwa
Senseiwa, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0/, via Wikimedia Commons. No changes were made.
‣
What age and gender typically present with this?
  • Men between 20-30 years
‣
What symptoms will they have? (2)
  • Lower back pain & stiffness
    • Early sign: Reduced lateral flexion of spine
  • Usually worse in the morning & improves with exercise
‣
What will be seen on examination?
  • Reduced lumbar mobility
    • Reduced lateral spinal movement (first sign)
    • Shöber's test: Distance between lines changes by < 5cm
  • Reduced chest expansion
‣
Name the other features.
  1. Aortic regurgitation
  2. AV node block
  3. Amyloidosis
  4. Apical fibrosis
  5. Anterior uveitis
  6. Achilles tendonitis
‣
What is the key XR finding for diagnosis?
  • Sacroiliitis
‣
What features are present on the following X-rays:
‣
X-ray 1
‣
Answer
  • Bamboo spine: Fusion of vertebrae
  • Dagger sign: Ossification of supraspinous and interspinous ligaments
Stevenfruitsmaak, CC BY-SA 3.0
Stevenfruitsmaak, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
X-ray 2
‣
Answer
  • Squaring of lumbar vertebrae: Osteitis of anterior corners
  • Syndesmophytes: Ossification of annulous fibrosus
James Heilman, MD, CC BY-SA 4.0
James Heilman, MD, CC BY-SA 4.0 creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons. No changes were made.
‣
How would you manage a patient with AS?
  1. NSAIDs & regular exercise
  2. Physiotherapy
  3. Anti-TNF drugs: Etanercept & adalimumab
    • Indicated after 2 NSAIDs have been tried
‣
Psoriatic arthropathy
‣
Why is this difficult to diagnose?
  • Often presents before cutaneous psoriasis
‣
How do you differentiate psoriatic arthropathy from other causes of joint pain? (3)
  1. Look for nail changes - Onycholysis/dactylitis (finger & toe inflammation)
  2. XR: Pencil-in-cup deformity
  3. DIP is commonly affected (differential for OA)
  4. Cutaneous rash
image
image
‣
Reactive arthritis/Spondyloarthropathy
‣
What features point towards reactive arthritis?
  • Recent infection within the last 4 weeks
  • 'Can't see, can't pee, can't climb a tree'
    • Conjunctivitis, balanitis, arthritis
  • Invx: No infection seen on joint aspiration (aseptic arthritis)
‣
What rash can be seen on the feet?
  • Keratoderma blenorrhagica
image
‣
Name the 3 stages of management.
  1. Analgesia & NSAIDs
  2. Intra-articular steroids
  3. Methotrexate/sulphasalazine
‣
Enteropathic arthropathy
‣
What is the typical presentation of this?
  • Peripheral joint inflammation occurring alongside a flare of Crohn's or UC
‣
Still's disease
‣
What are the common features?
  • High pyrexia (> 39°C) at night that settles by the morning
  • Arthralgia that worsens with the fever at night
  • Rash: salmon-pink, maculopapular
‣
What is this called in children?
  • JIA
‣
How is it managed?
  1. NSAIDs (1W trial)
  2. Steroids
  3. Methotrexate
‣
Crystal arthropathy
‣
Gout
‣
When is urate produced & where is it excreted?
  • Produced during the metabolism of DNA & RNA both of cells and dietary purines
  • Excreted through the kidneys
‣
What joint does this usually present in? Name 3 others. (4)
  1. 1st MTP joint - Great toe
  2. Knee
  3. Ankle
  4. Wrist
‣
What is found on joint aspiration?
  • Strong-negatively birefringent needle-shaped crystals
Gabriel Caponetti, CC BY-SA 3.0
‣
What are the radiological features? (3)
  1. Joint space retained
  2. Joint effusion
  3. 'Punched out' erosions (well-defined)
‣
Name 6 RFs for gout.
  • ↑ production: Cell breakdown
    1. Myelo-/lympho-proliferative disease (leukaemia)
    2. Chemotherapy
    3. Severe psoriasis
  • ↓ excretion
    1. Diuretics - thiazide
    2. CKD
    3. Lead toxicity
‣
What is defined as a high urate?
  • > 450
‣
How is it acutely managed?
  1. NSAIDs (naproxen + PPI)

OR

  1. Colchicine - SE: Diarrhoea
  2. PO steroids
  3. Intra-articular steroids
‣
How is it managed in the long-term? When is this indicated?
  • Allopurinol
    • Indicated: After first attack of acute gout
    • Wait for the acute episode to settle before starting as may worsen it
‣
What is the urate target for successful long-term management?
  • Management < 300
‣
Pseudogout
‣
What crystals are seen in the joint?
  • Calcium pyrophosphate
‣
Name 3 RFs.
  1. Haemochromatosis
  2. Hyperparathyroidism - Calcium
  3. Acromegaly
‣
What joints are commonly affected? (3)
  • Knee
  • Shoulder
  • Wrist
‣
What is seen on XR?
  • Chondrocalcinosis - Linear calcification of the articular cartilage
image
‣
What is seen on joint aspiration?
  • Weak-positively birefringent rhomboid-shaped crystals
  • No bacteria - exclude septic arthritis
Mikael Häggström, M.D. - Author info - Reusing images- Conflicts of interest: NoneMikael HäggströmConsent note: Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC0, via Wikimedia Commons
Mikael Häggström, M.D. - Author info - Reusing images- Conflicts of interest: NoneMikael HäggströmConsent note: Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC0, via Wikimedia Commons
‣
How is it managed? (2)
  • NSAIDs
  • Steroids (PO → intra-articular)
‣
Connective tissue disease
‣
Autoimmune
‣
Systemic lupus erythematosus (SLE)
‣
What age range and gender usually present with this?
  • Women
  • Afro-caribbean
  • 20-40 years
‣
What is the pathophysiology?
  • Antibodies to the cell nucleus & DNA form (type III hypersensitivity) → Systemic inflammation
‣
Features - How does it manifest in the following system:
‣
Skin
  • Photosensitive malar rash (nasolabial sparing)
  • Scaly, erythematous, well-demarcated rash
‣
Cardiac & respiratory
  • Pericarditis
  • Pleurisy
‣
MSK
  • Arthritis (no XR changes - non-erosive)
  • Arthralgia
‣
Renal
  • Glomerulonephritis
‣
What is a typical presentation of drug-induced lupus?
  • A patient presents with SLE features after starting a drug, commonly arthralgia, myalgia and cutaneous manifestations
    • ‣
    What antibody is diagnostic?
    • Anti-histone
    ‣
    What drugs commonly cause it?
    1. Hydralazine
    2. Procainamide (anti-arrhythmic)
    3. Isoniazid
    4. Phenytoin
‣
How do you investigate it?
  • Antibodies: ANA, anti-dsDNA, anti-smith
  • ↓ complement (C3 & C4)
  • FBC: Normocytic anaemia of chronic disease
  • Urinalysis - Lupus nephritis
‣
How is it monitored?
  • ESR
‣
What is first-line for mild disease?
  • Hydroxychloroquine & avoiding sun/suncream
‣
What may be used in more severe disease?
  • NSAIDs, steroids
  • Methotrexate, azathioprine, tacrolimus
  • Biologics - Rituximab
‣
Systemic sclerosis (scleroderma)
‣
What does sclerderma mean?
  • Sclero - hardening, derma - skin
‣
What is it?
  • Autoimmune connective tissue disease leading to fibrosis, affecting the skin and internal organs
‣
What are the 2 main patterns of disease?
  1. Limited cutaneous
    2. ‣
    What are the features of this? (Follow-on Qs)

    CREST syndrome

    ‣
    How does sclerodermic skin look?
    • Tight, shiny skin without normal skin folds
    ‣
    How does oesophageal dysmotility present?
    • Heartburn
    ‣
    What is sclerodactyly?
    • Thickening of skin on the fingers reduces their range of motion
    • Skin can become so tight that it breaks & ulcerates
    ‣
    What are telangiectasia?
    • Dilated small blood vessels with a fine, thready appearance
  2. Diffuse
    3. ‣
    How is this different?
    • All of the features above and internal organs are affected
    ‣
    Give examples of effects. (4)

    Connective tissue of organs undergoes fibrosis, therefore causing:

    • CV: HTN (↑ SVR), CHD
    • Lung: Pulmonary HTN/fibrosis (sclerosis)
    • Kidney: GN, scleroderma renal crisis (combination of HTN & AKI)
‣
What antibodies do you need to test for?
  1. ANA - Positive in most
  2. Anti-centromere antibodies - Limited cutaneous
  3. Anti-SCL-70 antibodies - Diffuse
‣
Why do you do nailfold capillaroscopy?
  • Examines the health of peripheral capillaries
  • Differentiates idiopathic Raynaud's (normal capillaries) from SS (abnormal)
‣
How are they managed?

MDT approach:

  1. Lifestyle: Avoid smoking, skin stretching, emmolients, avoiding cold
  2. Medical:
    • Steroids, immunosuppression
    • Raynauds → Nifedipine
    • Oesophagus → Omeprazole (acid), metoclopramide (motility)
‣
Polymyositis/Dermatomyositis
‣
What is the difference between the two?

Myositis - Muscle inflammation

  • Poly: Inflammation of the muscles
  • Dermato: Inflammation of the skin & muscles
‣
What symptoms do they often have?
  • Proximal muscle weakness (PMR = stiffness)
‣
What is the key investigation when diagnosing this & what result are you looking for?
  • Creatine kinase (released from muscles when damaged)
  • > 1000 U/L
‣
What do you need to consider when seeing a patient with this condition?
  • Is there an underlying malignancy?
    • This is commonly a paraneoplastic condition
    • Lung, breast, ovarian & gastric cancer
‣
What does the followinng picture show:
Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider, CC BY-SA 3.0
‣
Answer
  • Gottron's papules
‣
What does this signify?
  • Dermatomyositis
‣
What antibodies are found in the two types?
  1. Anti-Jo-1
  2. ANA
‣
What can give a definitive diagnosis?
  • Muscle biopsy
‣
What is the first-line treatment for both?
  • Corticosteroids
‣
Congenital
‣
Marfan syndrome
‣
What is the inheritance pattern & pathophysiology?
  • Autosomal dominant mutation in the gene coding for fibrillin, an important component of connective tissue → Increased elasticity
‣
Name 4 features.
  1. Arachnodactyly → Long fingers
  2. Hypermobility of joints
  3. Pectus excavatum/carinatum
  4. Tall, slender build
‣
Name 2 cardiac complications & 1 respiratory.
  1. Aortic sinus dilation (90%) (Also: Dissection)
  2. Mitral valve prolapse (75%)
  3. Recurrent pneumothoraces
‣
How is it monitored & managed?
  • Monitored: Annual echocardiogram
  • Managed: Beta-blocker/ACE-i
‣
Ehlers-Danlos syndrome
‣
What is the inheritance pattern?
  • Autosomal dominant
‣
What is the pathophysiology?
  • Type III collagen defect → Tissue elasticity → Hypermobility
‣
What are the features?
  • Skin elasticity
  • Joint hypermobility
‣
What is used to assess hypermobility?
  • Beighton score
‣
Name 2 complications.
  • Recurrent joint dislocation
  • Mitral regurgitation
‣
Bone density
‣
Osteoporosis
‣
Name the 2 main risk factors.
  1. Corticosteroids
  2. Menopause
‣
Name 3 endocrine risk factors.
  1. Premature menopause
  2. Hyperthyroidism
  3. Hyperparathyroidism
  4. Hypogonadism (primary/secondary)
‣
How do you measure the extent of osteoporosis? How is it quantified?
  • DEXA scan
  • T-score
    • T > -1.0 → Normal
    • -1.0 > T > -2.5 → Osteopenia
    • T < -2/5 → Osteoporosis
‣
Management?
‣
Primary prevention?
  • Conservative: Stop smoking, increase exercise, limit alcohol, Vit D replacement if not exposed to sufficient sunlight
  • First line: Bisphosphonates eg Alendronic acid (SE: Reflux so specific instructions for taking it)
  • Second line: Denosumab (monoclonal antibody)
‣
Secondary prevention?
  • Bisphosphonates
  • Raloxifene (binds to oestrogen receptors)
‣
What constitutes secondary prevention?
  • Someone who has previously had a fragility fracture
  • Women aged 75 years and older
    • For these people you assume they already have osteoporosis even if they're not had a fragility fracture previously. So you'd just treat rather than do a DEXA scan first for these patients.
    • *No guidance for men- but assume you'd treat men >75yo the same as women
‣
If on steroids, how does management of osteoporotic risk differ?
  • < 65 years old: DEXA scan (then treat if T score < - 1.5.
  • > 65 years old: Start alendronate immediately.
‣
Paget's bone disease
‣
Introduction:
‣
What is Paget's disease?
  • Raised, uncontrolled bone turnover
‣
What is the underlying pathophysiology?
  • Overactivity of osteoclasts → Increased bone breakdown → Increased osteoblast activity → Formation of very dense areas of poorly formed bone
‣
How common is it?
  • 5% of the population
  • Only 5% of people with disease are symptomatic
‣
What is the stereotypical presentation?
  • Older male presents with bone pain and has an isolated ↑ ALP
    • ‣
    What bones are most commonly affected?
    • Long bones - Femur, tibia
    • Skull
    • Pelvis/spine
‣
How is it investigated? (2)
  • XR of symptomatic area
  • LFTs - Isolated ↑ ALP
Jmarchn, CC BY-SA 3.0
‣
How is it managed?
  • Bisphosphonates - PO risedronate
‣
What are the main complications? (3)
  1. Deafness
  2. Fractures
  3. Bone sarcoma
‣
Osteopetrosis
‣
What is this?
  • AR genetic condition → ↑ Bone density.
  • XR: 'Marble bone'
‣
Management?
  • Depends on severity, symptoms and patient factors
  • Can include Vit D supplements, steroids, surgery
‣
Osteogenesis imperfecta
‣
What is it?
  • Autosomal dominant abnormality of collagen metabolism resulting in bone fragility and fractures
‣
What are the characteristic features?
  • Fractures following minor trauma
  • Blue sclera
  • Otosclerosis → Deafness
‣
What do investigations show?
  • They’re NORMAL: Adjusted calcium, phosphate, parathyroid hormone and ALP
‣
🌯 Vasculitis
‣
Giant cell arteritis
‣
Temporal arteritis
‣
What are the main features? (5)
  1. Scalp tenderness
  2. Headache
  3. Jaw claudication (headache worse when talking for prolonged periods)
  4. Visual changes (blurred vision)
  5. > 65 years
‣
How is it investigated (& what value is diagnostic)? (2)
  1. ESR > 50 → GCA
  2. Temporal artery biopsy (skip lesions mean this test isn't specific)
‣
How is it managed? (2)
  • Acute: Prednisolone 60mg STAT → Rapid recovery
  • Urgent review by ophthalmology
‣
Polymyalgia rheumatica (PMR)
‣
What is present on histology? (3)
  • Giant cell vasculitis with infiltration of lymphocytes & inflammation causing a small lumen
image
‣
What is the characteristic presentation?
  • 65 year old presenting with proximal limb stiffness without muscle weakness/wasting (shoulder/hip)
‣
How do you differentiate this from polymyositis?
  • No weakness in PMR, just stiffness. Weakness in polymyositis
  • Normal CK in PMR
‣
How do you investigate it?
  • ESR > 40 → PMR
  • CK (rule out polymyositis) & EMG normal
  • Biopsy for histology
‣
How do you treat it?
  • Prednisolone 60mg STAT → Rapid recovery

What is the diagnosis?

‣
A 17 year old patient presents with severe asthma and elevated eosinophil levels on FBC. Their pANCA is positive.
  • Eosinophilic granulomatosis with polyangiitis
  • Associated with sinusitis, asthma, purpurae, peripheral neuropathy and glomerulonephritis
‣
A 21-year-old woman goes to the emergency department with some chest pain. The registrar is troubled that he cannot feel either radial pulse, even though the triage sheet shows the patient to be hypertensive.
  • Takayasu’s arteritis ("pulseless disease")
  • Causes large arteries to form aneurysms or become narrowed & blocked
‣
An 8 year old patient who had tonsillitis 1 week ago presents with joint pain, abdominal pain and the following rash affecting the lower limbs & buttocks:
Peter Rammstein, CC BY 3.0
Peter Rammstein, CC BY 3.0 creativecommons.org/licenses/by/3.0, via Wikimedia Commons. No changes were made.
‣
Diagnosis?
  • Henoch-Schonlein purpura
‣
What investigation is key?
  • U&E to look for renal involvement as he may have IgA nephropathy
‣
A young, male smoker presents with an acutely ischaemic right foot with absent pulses.
  • Buerger's disease (Non-atherosclerotic vasculitis → Occlusive thrombus)
    • Corkscrew-shaped collateral vessels distally
      • ‣
      What is the main management of this?
      • Smoking cessation
‣
A patient with known Hepatitis B presents with the following rash:
‣
Diagnosis?
  • Polyarteritis nodosa - Results in aneurysms & thrombosis
    • Rash: Livedo reticularis
    • Affects skin, GI tract, kidneys & heart
Nantsupawat T et al, CC BY-SA 3.0
Nantsupawat T et al, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons
‣
A patient presents with recurrent epistaxis, crusty nasal secretions & haemoptysis. Their nose looks as follows:
Vw38, CC BY-SA 4.0
Vw38, CC BY-SA 4.0 creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons. No changes were made.
‣
Diagnosis?
  • Granulomatosis with polyangiitis
‣
What antibodies will she have?
  • c-ANCA
‣
What will the CXR show?
  • Pulmonary infiltrates/consolidation from vascular damage
‣
What other organ does it commonly affect?
  • Kidney causing GN
    • ‣
    This makes it a differential for what condition?
    • Goodpastures as can cause GN & haemoptysis
‣
A 28 year old female presents with recurrent DVT on a history of SLE.
  • Antiphospholipid syndrome
    • ‣
    Antibody?
    • Anti-cardiolipin
    ‣
    Investigations?
    • FBC: Thrombocytopenia
    • Clotting: Prolonged APTT
    ‣
    Management?
    1. Lifelong warfarin: INR target 2-3
    2. DVT occurs on warfarin: Increase target INR to 3-4
‣
A patient has a history of recurrent oral ulcers and genital ulcers. They have now presented with anterior uveitis.
  • Behçets syndrome (clinical diagnosis)
    • ‣
    What else is this associated with?
    • Erythema nodosum
‣
💂🏼‍♂️ Antibodies

Name the condition most commonly associated with the following antibodies:

‣
Anti-CCP
  • Rheumatoid arthritis
‣
Anti-SCL-70
  • Diffuse systemic sclerosis
‣
Anti-centromere
  • Limited cutaneous systemic sclerosis (CREST)
‣
Anti-histone
  • Drug-induced SLE
‣
Anti-Ro & anti-La
  • Sjogren's syndrome
‣
Anti-Jo-1
  • Dermatomyositis
‣
Anti-cardiolipin
  • Anti-phospholipid syndrome
‣
Anti-Smith
  • SLE
‣
pANCA/MPO-ANCA
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
    • Also can be raised in IBD
‣
cANCA
  • Granulomatosis with polyangiitis (Wegener's)
‣
🤔 Other
‣
Sjogren's syndrome
‣
What is the pathophysiology of this condition?
  • Antibodies form against exocrine glands → Dry mucosal surfaces
‣
It can be primary, but if secondary what is it usually associated with?
  • Rheumatoid arthritis
‣
What malignancy are these patients at risk of?
  • Lymphoid malignancy
‣
What systems are affected?
  • Eyes - Dry (keratoconjunctivitis sicca)
  • Mouth - Dry
  • Vagina - Dry
‣
How is it managed?
  • Artificial saliva & tears
  • Pilocarpine - Stimulates saliva production
‣
Raynaud's phenomenon
‣
How does primary differ from secondary?
  • Primary:
    • Bilateral
    • Presents in 30-40 year olds
  • Secondary:
    • Unilateral
    • Patient has positive inflammatory markers/comorbidities
‣
What is the pathophysiology?
  • Arterial spasm within the hands → Reduced blood flow (pale skin) → Tissue hypoxia (cyanosed skin) → Reperfusion (Very red skin)
‣
Name 2 secondary causes.
  • Scleroderma (most common)
  • Rheumatoid arthritis
‣
What is first-line management?
  • CCB - Nifedipine
‣
Fibromyalgia
‣
What is the typical presentation? (2)
  • Widespread pain throughout the body
  • With tender points
‣
What is the epidemiology?
  • Women
  • 30-50 years
‣
How is it diagnosed?
  • Assessment of the 18 tender points on the body
  • ≥ 11/18 → Likely fibromyalgia
‣
How is it managed? (3)
  • Lifestyle: Aerobic exercise
  • CBT
  • Drugs: Pregabalin, amitryptiline
‣
💊 Drugs
‣
Name side effects of the following drugs (Follow-on Qs):
‣
All immunosuppressants (1)
  • Myelosuppression → Neutropenia & infection risk
‣
Methotrexate (3)
  1. Pneumonitis
  2. Mucositis
  3. Myelosuppression
    4. ‣
    What needs to be monitored while a patient is on methotrexate?
    • FBC - Myelosuppression, folate deficiency (macrocytic anaemia)
    • LFT - Liver damage
    • U&E
    ‣
    How is methotrexate toxicity managed?
    • Folinic acid
    ‣
    What drug can never be given with methotrexate?
    • Trimethoprim/co-trimoxazole
    ‣
    How long do they need to be off methotrexate before trying for a baby?
    • 6 months
‣
Corticosteroids (5)
  1. Cushing's syndrome (SWEDISH)
  2. Osteoporosis
  3. Addison's (when withdrawn fast)
  4. Hypertension
  5. GORD
  6. Hyperglycaemia
‣
Ciclosporin (5)
  1. Hypertrophy of the gums
  2. Hypertrichosis
  3. Hypertension
  4. Hyperkalaemia
  5. Hyperglycaemia (diabetes)
‣
Leflunomide (2)
  • Hypertension
  • Peripheral neuropathy
‣
Sulfasalazine (1)
  • Male infertility (reduces sperm count)
‣
Hydroxychloroquine (1)
  • Bull's eye retinopathy - may result in severe and permanent visual loss
    • Monitor visual acuity
‣
Anti-TNF (1)
  • Reactivation of TB or HepB
‣
Rituximab (2)
  • Night sweats
  • Thrombocytopenia
‣
Azathioprine (1)
  1. Pancreatitis
    2. ‣
    What should never be prescribed with this?
    • Allopurinol
‣
Which anti-inflammatory drug used for IBD is safe in pregnancy?
  • Azathioprine
‣
Alendronic acid
‣
Name 3 indications for alendronic acid.
  1. Osteoporosis
  2. Paget's disease
  3. Hypercalcaemia
‣
Name 3 adverse effects of alendronic acid.
  1. Pathological fractures along stress lines
  2. Oesophageal reactions - Oesophagitis, ulcers
  3. Osteonecrosis of jaw
‣
What advice needs to be given when prescribing alendronic acid?
  • Give 30 mins before breakfast (empty stomach)
  • Swallow whole with plenty of water
  • Stay sat/stood upright for 30 mins after taking drug

🧠 Neurology

‣
🧠 Central Nervous System
‣
Brain
‣
Headaches
‣
Primary
‣
Migraine
‣
What features can you get?
  • Premonitory phase: Yawning, mood changes etc
  • Unilateral throbbing headache (often)
  • Nausea and vomiting
  • Aura e.g. zig zag lines in vision
  • Photophobia
  • Impairs capacity to function: impairs activities of daily life
  • Can have triggers: varies between patients e.g. coffee, chocolate
‣
Pathophysiology
  • Cortical spreading depression: self-propogating
  • Meningeal nerves affected
‣
How long does it last?
  • 4-72 hours
‣
Management?
  • Stop analgesia (never treat headaches with analgesia) and caffeine
  • Acutely: Triptans
‣
2 options for prophylaxis?
  • Propanalol
  • Topiramate
‣
Trigeminal Autonomic Cephalgia
‣
Cluster headache
‣
What features can you get?
  • Excruciating pain around one eye (always affects same eye)
  • Eye redness, swelling, sweating, lacrimation
  • Runny nose
  • Restlessness- patient cannot sit still
‣
How long does it last, and how often?
  • 15 mins – 2 hours. Clusters occurs every 4 – 12 weeks typically
‣
What is the common trigger?
  • Alcohol
‣
Management?
  • High dose oxygen
  • Sumatriptan
  • High-dose prednisolone over 48h
  • Long term: Verapamil
‣
Name 3 other differentials.
  1. Paroxysmal hemicrania
  2. SUNCT
  3. Hemicrania continua
‣
Trigeminal neuralgia
‣
What is it?
  • Unilateral electric shock-like pains that are quick in both onset and termination, following the distribution of the trigeminal nerve.
    • Common triggers: Light touch, smoking, talking, and brushing teeth
‣
What can cause it?
  • Idiopathic (majority of cases)
  • Secondary: Tumour, vascular issues
    • ‣
    What features are suggestive of a secondary cause?
    • Sensory changes
    • Deafness or other ear problems
    • Pain only in the ophthalmic division of the trigeminal nerve or bilaterally
    • Optic neuritis / family history of MS
    • Age of onset before 40 years
‣
What’s the first-line management?
  • Carbamazepine
‣
Tension
‣
What features can you get?
  • Bilateral headache like a 'tight band across forehead', mild ache, non-disabling
‣
Management?
  • Reassurance
  • Basic analgesia
  • Relaxation techniques, hot towels to local area
‣
Secondary

Covered elsewhere: CNS infection, SAH, temportal arteritis, raised ICP, SOL, glaucoma, instracranial hypotension.

‣
Idiopathic intracranial hypertension (IIH)
‣
Who classically in exams gets this?
  • Obese women
‣
Management?
  1. Weight loss & close monitoring
  2. Carbonic anhydrase inhibitors - Acetazolamide
‣
What are your differentials for facial pain?
  1. Trigeminal neuralgia
  2. Post-herpetic neuralgia
  3. TMJ syndrome
  4. Giant cell arteritis
  5. Dental pain
‣
Vascular
‣
Stroke
‣
What scoring system is useful in recognising stroke?
  • Rosier score: Any score above 0 indicates stroke is likely
    • Lose points: Syncope/seizure
    • Gain points: Weakness
image
‣
A patient presents with stroke, what invstigation is key & why?
  • CT head: Ischaemic or haemorrhagic?

Classifying:

‣
Ischaemic (85%)
‣
Classification
‣
What are the subtypes & features of them?
  • Cerebral - Contralateral hemiplegia (flaccid then spastic), contralateral hemi-sensory loss, dysphasia, contralateral homonymous hemianopia & contralateral visuo-spatial deficit
  • Brainstem - Quadriplegia, cranial nerve deficits & disorders of consciousness (e.g. locked-in syndrome)
  • Lacunar (basal ganglia) 1 of 5 syndromes:
    • Pure motor
    • Pure sensory
    • Sensorimotor
    • Ataxic hemiparesis
    • Dysarthria
‣
Brainstem strokes:

Name the artery affected from the presentation:

‣
Complete quadriparesis and lower cranial nerve dysfunction, with preserved consciousness.
  • 'Locked in syndrome': Basilar artery
‣
Ipsilateral oculomotor nerve palsy and contralateral hemiparesis.
  • Weber syndrome: Branches of upper basilar and proximal posterior cerebral arteries
Madhero88, CC BY-SA 3.0
Madhero88, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
Loss of contralateral pain/temperature on the body, ipsilateral facial paralysis, ipsilateral deafness and tinnitus, ipsilateral ataxia.
  • Lateral pontine syndrome: Anterior inferior cerebellar artery
    • Blood supply to the pons is lost, so these nerves are affected
‣
Ipsilateral Horner's syndrome, ipsilateral loss of pain and temperature sensation on the face, and contralateral loss of pain and temperature sensation over the contralateral body
  • Lateral medullary syndrome: PICA
    • C.N. IX, X & XII affected - Dysphagia (another presentation)
‣
Diagram: Cerebral Vascular Territories
derivative work: Frank Gaillard (talk)Brain_human_sagittal_section.svg: Patrick J. Lynch, medical illustrator, CC BY-SA 3.0
derivative work: Frank Gaillard (talk)Brain_human_sagittal_section.svg: Patrick J. Lynch, medical illustrator, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
derivative work: Frank Gaillard (talk) Brain_stem_normal_human.svg: Patrick J. Lynch, medical illustrator, CC BY-SA 3.0
derivative work: Frank Gaillard (talk) Brain_stem_normal_human.svg: Patrick J. Lynch, medical illustrator, CC BY-SA 3.0 creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. No changes were made.
‣
What is the Bamford-Oxford classification?

What symptoms are required for:

‣
Total anterior circulation infarct (ACA + MCA)
  • Contralateral hemiplegia or hemiparesis, AND
  • Contralateral homonymous hemianopia, AND
  • Higher cerebral dysfunction (e.g. aphasia, neglect)
‣
Partial anterior circulation infarct (ACA / MCA)
  • 2/3 of the above
  • Higher cerebral dysfunction alone
‣
Lacunar stroke (Deep perforating arteries)

One of the following:

  • Cerebellar dysfunction
  • Conjugate eye movement disorder
  • Bilateral motor/sensory deficit
  • Ipsilateral cranial nerve palsy with contralateral motor/sensory deficit
  • Cortical blindness/isolated hemianopia
‣
Investigations
‣
What is most commonly used investigation?
  • CT head (non-contrast)
‣
What is the gold standard investigation?
  • Diffusion-weighted MRI
‣
How would you investigate if this is secondary to carotid stenosis?
  • Carotid ultrasound
‣
Management
‣
What is the immediate management?
  1. Aspirin 300mg
  2. Thrombolysis with alteplase (if within 4.5 hours of symptom onset)
    3. ‣
    What is alteplase?
    • A tissue plasminogen activator that rapidly breaks down clots, puts patient at risk of intracranial or systemic haemorrhage
  3. Thrombectomy (within 6 hours) - mechanical removal of the clot
‣
When would you need to do a craniectomy?
  • Malignant MCA syndrome - Swelling around area causes midline shift and raised ICP
‣
What secondary prevention may be needed?
  1. Lifestyle: Diet, exercise, smoking cessation
  2. Manage risk factors: Hypertension, DM, etc.
    • Patients with carotid artery disease may need carotid endarterectomy or stenting.
  3. Medications:
    • Clopidogrel 75mg OD for life (or dipyridamole 200mg BD)
    • Atorvastatin 80mg (but not immediately started)
‣
What is the score to classify disability in stroke?
  • Modified Rankin Scale
‣
Haemorrhagic (15%)
‣
What are the key risk factors? (6)
  • Age
  • Male
  • Family history
  • Anticoagulation, sympathomimetic drugs (such as cocaine & amphetamines)
  • Haemophilia, cerebral amyloid angiopathy/hypertension, AVM
  • Alcohol
‣
How would you manage a haemorrhagic stroke if patient is on warfarin?
  1. Stop warfarin
  2. Give IV vitamin K 5mg
  3. Give prothrombin complex concentrate (or FFP if not available)
‣
TIA
‣
What criteria are used to assess a TIA?

ABCD-2

  • Age ≥ 60 years (1)
  • BP > 140/90 (1)
  • Clinical features
    • Unilateral weakness (2)
    • Isolated speech impairment (1)
  • Duration
    • > 60 mins (2)
    • 10 - 59 mins (1)
  • 2
‣
What score in this criteria represents high risk & how are these managed?
  • Score ≥ 4
  • 300mg of aspirin immediately, then assessed by a specialist within 24 hours
‣
How are all TIA patients managed if on anticoagulation?
  • Immediate referral to A&E for CT head to look for bleed
‣
What are the medical management options?
  1. Control RFs: HTN, lipids
  2. Antiplatelets: Aspirin 300mg for 2 weeks followed by clopidogrel 75mg
  3. Anticoagulation: If TIA associated with AF
‣
When is carotid endarterectomy indicated?
  • Stenosis > 70% on doppler
‣
Intracranial bleeds
‣
Epidural
‣
How is this surgically managed?
  • Ligation of the artery
‣
Subdural
‣
How is this surgically managed?
  • Clot not organised: Burr hole craniostomy
  • Clot organised: Craniotomy
‣
Sub-arachnoid
‣
What is this commonly associated with?
  • Polycystic kidney disease (linked to berry aneurysms)
‣
How are they investigated?
  1. Urgent CT head - If positive begin treatment, if negative see below
  2. LP 12 hours after headache onset - Xanthochromia
‣
How is this surgically managed?
  1. Endovascular coiling
  2. Surgical clipping
‣
Why do they start nimodipine after surgery?
  • Used to prevent vasospasm of the cerebral vessels, optimising brain perfusion
‣
Basal skull fracture
‣
What are the key features?
  1. 'Panda/raccoon eyes' - Periorbital ecchymoses
  2. CSF rinorrhoea/otorrhoea
  3. 'Battle sign' - Retroauricular ecchymoses
image
‣
Venous sinus thrombosis
‣
What features are suggestive of this?
  • Prothrombotic RFs: Smoking, FH of DVT/SLE, COCP
  • Sudden onset severe headache - "Thunderclap"
  • Nerve compression → Papilloedema, eye movement disorders
‣
What is the gold-standard investigation?
  • MR venogram
‣
Movement disorders
‣
Parkinson's
‣
Features?
‣
Cardinal motor features?
  • Resting tremor
  • Cogwheel rigidity
  • Bradykinesia
‣
Other features?
  • Shuffling gait
  • Masked facies
  • Hypophonia
  • Autonomic dysfunction
  • Depression
  • Dementia
‣
What is the first-line management, & how is the patient's QoL relevant?
  • Motor symptoms affecting QoL: Levodopa
  • QoL not affected: Dopamine agonist
‣
What are the common SEs of treatment?
  • Hypotension
  • Restlessness
  • GI upset
‣
What personality changes can dopamine agonists cause?
  • Increased impulsiveness
‣
What are the side effects of long-term levodopa treatment?
  • Drug-induced dyskinesias: Writhing and uncoordinated movements of the limbs
  • On-off effect: Random fluctuations in drug effect
  • Wearing off over time: Symptoms return before taking the next dose
‣
What features are suggestive of drug-induced parkinsonism?
  • Bilateral tremor that has come on after taking dopamine antagonists (antipsychotics, antiemetics)
‣
What are the parkinson's plus syndromes? (4)
  1. Lewy body dementia - Fluctuations in cognitive impairment and visual hallucinations, often before parkinsonian features occur
  2. Progressive supranuclear palsy - Vertical gaze palsy
  3. Multiple systems atrophy - Autonomic features: Postural hypotension, incontinence & impotence
  4. Cortico-basal degeneration - Spontaneous activity by an affected limb (alien limb), or akinetic rigidity of that limb
‣
Benign essential tremor
‣
What features allow you to distinguish it from a Parkinsons tremor?
  • Symmetrical (Parkinsons is asymmetrical)
  • 5-8 hertz (Parkinsons is 4-6)
  • Improves at rest (Parksinsons is worse at rest)
  • Improves with alcohol (Parkinsons has no change with alcohol)
‣
Huntington's chorea
‣
What is the cause?
  • Autosomal dominant trinucleotide (CAG) repeat disorder coding for huntingtin protein.
‣
What is the triad?
  1. Dominant inheritance - Family history
  2. Choreoathetosis - Uncontrollable, purposeless movements
  3. Dementia
‣
What is seen on MRI?
  • Atrophy of caudate nucleus & putamen
‣
Dystonia
‣
What is it?
  • Prolonged, often painful, muscle contraction
‣
What medications commonly cause this?
  • Dopamine antagonists: Antipsychotics, antiemetics (metoclopramide)
‣
How does dystonia commonly present? (3)
  • Oculogyric crisis (upward eye deviation)
  • Torticollis (cervical dystonia)
  • Trismus (lockjaw)

Case:

‣
A 17-year-old girl presents with a resting tremor in her left arm. She is dysarthric and ataxic. An ECG reveals first-degree heart block. Diagnosis?
  • Wilson's disease
  • May also have psychiatric and hepatic features due to damage via copper deposition
‣
Epilepsy
‣
What are your differentials & features suggestive of them?
  1. Generalised seziure: Post-ictal confusion, lateral tongue biting, Todd's paresis (focal neurological deficit)
  2. Syncope: No post-ictal confusion, hot, sweaty & lightheaded before
  3. Stokes-Adams attack (arrhythmogenic syncope): Abrupt onset causing significant injury
  4. Psychogenic non-epileptic attack (pseudoseizures) - Often > 30 mins, in front of others, tongue biting is rare / front biting
  5. Hemiplegic migraine
  6. CVA
‣
Features:
‣
How does a myoclonic seizure commonly present?
  • Sudden jerk of a limb, trunk, or face
  • Worse after alcohol and when tired
‣
What lobe is responsible for a focal seizure with the following features:
‣
Automatisms (e.g. lip-smacking); déjà vu or jamais vu, emotional disturbance (eg. sudden terror); olfactory, gustatory, or auditory hallucinations
  • Temporal lobe
‣
Motor features such as Jacksonian features, dysphasia or Todd's palsy.
  • Frontal lobe
‣
Tingling and numbness followed by motor symptoms
  • Parietal lobe
‣
Spots and lines in the visual field.
  • Occipital lobe
‣
What is Todd's paresis?
  • Post-ictal paresis - Weakness after a seizure, can appear like a stroke presentation
‣
What is Hoover's sign?
  • Used to differentiate functional from organic leg paresis
  • Lie on bed, lift leg up, if the leg on the bed pushes down against your hand it's more likely to be psychogenic
‣
Management:
‣
What is first-line for generalised & focal seizures (long-term), respectively?
  • Generalised: Sodium valproate (non-childbearing age) / lamotrigine (childbearing age)
  • Focal: Carbamazepine
‣
Which anti-epileptic is safe to use in pregnancy?
  • Lamotrigine - Use in all women of childbearing age
‣
What anti-epileptics have the following SEs:
‣
Blurred vision, nystagmus and poor coordination
  • Carbamazepine
‣
Hepatotoxicity, pancreatitis, hair thinning, weight gain
  • Sodium valproate
‣
Gingival hyperplasia, acne, hirsutism & peripheral neuropathy
  • Phenytoin
‣
Large blisters (SJS)
  • Lamotrigine (generally well tolerated)
‣
Status epilepticus:
‣
How do you manage this?
  1. ABCDE - Remember BM is very important
  2. Benzodiazepine (Give second dose after 5 mins if seizure doesn't stop):
    • Hospital: IV lorazepam
    • Primary care: Buccal midazolam/rectal diazepam
  3. IV phenytoin / phenobarbital
  4. Intubate & ventilate
‣
Paediatric:
‣
Infantile spasms
‣
Features?
  1. Jacknife flexion of upper limbs
  2. Clusters
‣
First-line management?
  • Digabatrin
‣
West syndrome:
‣
Triad?
  1. Spasms
  2. Hypsarrhythmia
  3. Developmental regression
‣
What are they at risk of in adulthood?
  • Lennox-Gustau: Seizures & mental handicap
‣
Tuberous sclerosis
‣
What are the cutaneous manifestations?
  1. Ash leaf spots
  2. Angiofibromas
  3. Retinal hamartoma
‣
What may be seen on EEG?
  • Hypsarrhythmia in children
‣
How can you trigger an absence seizure?
  • Hyperventilation for 30 seconds
  • Stress
‣
What is a classic presentation of benign rolandic epilepsy?
  • Morning sensory change
  • EEG: Centrotemporal spikes
‣
Space occupying lesion
‣
What tumours commonly metastasise to the brain? (3)
  1. Breast
  2. Lung
  3. Melanoma
‣
What are the common primary CNS tumours?
  1. Meningioma (benign)
  2. Glioblastoma multiforme (malignant)
‣
Cerebral abscess
‣
RFs?
  • URTI in immunosuppressed patient (steroids, HIV etc)
‣
Features?
  • CT head shows ring enhancing lesion
  • Compression of structures causes spastic hemiparesis and confusion
‣
Management of cerebral abscess?
  • IV antibiotics
  • Surgical drainage
‣
Cerebellum
‣
What features are you looking for OE?
  • Dysdiadochokinesia (an inability to perform rapid alternating hand movements)
  • Ataxia (a broad-based, unsteady gait)
  • Nystagmus (involuntary eye movements)
  • Intention tremor (seen when the patient is asked to perform the 'finger-nose test')
  • Slurred speech
  • Hypotonia
‣
An alcoholic patient has Wernicke's encephalopathy. What is the triad?
  1. Opthalmoplegia
  2. Ataxia
  3. Confusion
    4. ‣
    What else can cause Wernicke's?
    • Hyperemesis gravidarum, malnutrition, bariatric surgery
    ‣
    How are they managed?
    • IV pabrinex (B1)
    ‣
    When managing alcoholics with a low BM, what needs to be given first?
    • Give IV pabrinex first as if not done giving glucose can cause Wernicke's
‣
What are your differentals in someone presenting with cerebellar dysfunction?
  • Posterior circulation stroke
  • Traumatic causes include trauma to the posterior fossa
  • MS
  • Metabolic - Alcohol
  • Infective - Lyme disease
  • Neoplastic causes include primary tumours (e.g. cerebellopontine angle tumour, acoustic neuroma) and secondary tumours (metastases e.g. breast cancer, lung cancer)
  • Drugs - phenytoin and carbamazepine
  • Congenital/hereditary causes include Friedrich's ataxia, and the spinocerebellar ataxias
‣
Spinal cord
‣
Acute spinal compression
‣
How do symptoms differ between spinal cord compression and cauda equina?
  • Cauda equina patients have saddle anaesthesia & loss of anal tone, whereas cord compression doesn't
    • Loss of anal tone → Constipation / incontinence
  • Cord ends at L1
‣
What is a common cause of cauda equina?
  • Lumbar disc herniation
‣
How is this definitively investigated?
  • Whole spine MRI
‣
How is it managed?
  • Steroids
  • Surgical decompression within 48 hours
‣
Cervical spondylosis
‣
What features suggest this?
  • Neck pain, radiculopathy (nerve root pinching) causing flaccid upper limb paresis, and myelopathy causing spastic paraparesis (and can involve the upper limbs)
  • Longer history (6-8 months)

Cases:

‣
Following abdominal surgery a patient has loss of pain, temperature, motor and autonomic function below the umbilicus. Proprioception & vibration are preserved. Diagnosis?
  • Anterior spinal artery occlusion
‣
14 year old has a history of falls, his grandad had similar problems. OE he has wasting of the lower limb muscles, spastic hypertonia, reduced power, ankle reflexes, and upgoing plantars. Diagnosis?
  • Friedrich's ataxia - Autosomal recessive neurodegenerative disease of the spinal cord
    • ‣
    Based on the symptoms above, what has been affected?
    • Corticospinal tracts - Spastic hypertonia, upgoing plantars
    • Peripheral nerves - LMN signs of wasting, absent reflexes
    • Spinocerebellar tracts
    • Dorsal columns - Vibration & proprioception
    ‣
    What other features are characteristic?
    • Pes cavus (don't confuse with CMT - only LMN signs)
    • Scoliosis (due to muscle weakness)
‣
25 year old patient has a ‘cape-like’ (neck and arms) loss of sensation to pain and temperature but preservation of light touch, proprioception and vibration
  • Syringomyelia - Spinothalamic tracts affected first, then corticospinal as it progresses, dorsal columns are spared as the syrinx pushes laterally
    • ‣
    What are the common causes?
    • Chiari malformation
    • Trauma
    • Tumour
    ‣
    What area of the spinal cord does the spinothalamic tract sit in?
    • Anterior white commisure
‣
Both
‣
Infection
‣
Meningitis
‣
What organism is likely responsible for neonatal meningitis?
  • Group B Streptococci
‣
Between 6 - 60 years, what are the 2 main bacteria causing meningitis?
  • N. meningitidis
  • S. pneumoniae
‣
Between 3 months - 6 years, what additional organism can cause disease?
  • H. influenzae
‣
An immunocompromised patient has meningitis signs, a very high opening pressure on LP, how do you confirm fungal infection? Management?
  • Cryptococcus infection - India ink staining
  • IV amphoterecin B & PO flucytosine followed by PO fluconazole (8W)
‣
What is the immediate primary care management if meningitis is suspected?
  • IM benzylpenicillin
    • If IV access is available then give this IV
‣
What is the secondary care management? (3)
  1. IV Cefotaxime/ceftriaxone (after blood cultures)
  2. IV Dexamethasone (to reduce oedema)
  3. Lumbar puncture (unless there are signs of raised ICP, in which case ICU referral is needed)
‣
What is the immediate antibiotic management in a 1 month old child with suspected meningitis?
  • IV cefotaxime (covers GBS)
‣
What is given to household for prophylaxis?
  • Ciprofloxacin
‣
Encephalitis
‣
What history features may be suggestive of encephalitis over meningitis?
  • Personality changes
‣
How would you investigate this? (2)
  1. CT head
  2. CSF viral PCR - Confirm HSV presence & subtype
  3. MRI brain - Bilateral involvement of the medial temporal lobes
‣
How is it managed?

2 weeks of:

  • 2g IV ceftriaxone BD
  • 10 mg/kg IV aciclovir TDS
‣
Lumbar puncture
‣
What is a contraindication for LP & how do you investigate for it?
  • ↑ ICP
  • CT head
‣
Defining values:
‣
How do you define low CSF glucose & when is it low?
  • Less than half of the plasma glucose
  • Low in bacterial/TB meningitis & viral encephalitis
‣
What are the common CSF compositions & when are they present?
  • Lymphocytes - Viral encephalitis/TB
  • Mononuclear cells - Viral meningitis
  • Neutrophils/polymorphs - Bacterial meningitis
‣
What is the CSF normal cell count and when is it changed?
  • Normal < 5
  • < 1000 - TB/viral meningitis
  • > 1000 - Bacterial meningitis (although can be lower)
‣
How can you use protein to differentiate?
  • > 1 - Bacterial or TB
  • < 1 - Viral
‣
Results:
‣
↓ glucose, ↑ protein, ↑ lymphocytes
  • TB meningitis
‣
↔︎ glucose, ↔︎/↓ protein, ↑ lymphocytes
  • Viral meningitis
‣
↓ glucose, ↑ protein, ↑ polymorphs
  • Bacterial meningitis
  • High protein & cell count
‣
↓ glucose, ↑ protein, ↑ lymphocytes
  • Viral encephalitis
‣
Micro: Gram negative diplococci
  • N. meningitidis
‣
Micro: Gram positive diplococci
  • S. pneumoniae
‣
MS
‣
What are the different types?
  1. Primary progressive
  2. Relapsing-remitting
  3. Secondary progressive
‣
What features are diagnostic?
  • At least 2 attacks of neurological dysfunction (relapses) over the previous 2 years
    • E.g. Optic neuritis (double vision & loss of colour vision in 1 eye)
‣
What is the triad of optic neuritis?
  1. Visual loss
  2. Periocular pain - Behind eye
  3. Dyschromatopsia - Loss of colour vision
‣
What is seen on LP?
  • Acellular, often with slightly raised protein,
  • Oligoclonal bands: Dark bands on Western Blot of CSF showing IgG
‣
How are relapses treated?
  • IV methylprednisolone
‣
What is used for long-term management?

Disease-modifying drugs:

  1. Interferon-beta
  2. Natalizumab (expensive & lots of SEs)
‣
What is Devic's disease?

Differential for MS, presenting with the triad of:

  1. Optic neuritis
  2. Transverse myelitis
  3. Positive NMO-IgG (an antibody targeting aquaporin 4)
‣
💪🏼 Peripheral Nervous System
‣
Cranial nerves
‣
Oculomotor
‣
What is a medical & surgical third nerve palsy?
  • Medical: Ptosis & down & out pupil - Diabetes, HTN, vasculitis
  • Surgical: Pupil dilation & pain in addition to above
‣
What can cause a surgical third nerve palsy?
  1. Posterior communicating artery aneurysm
  2. Cavernous sinus infection, thrombosis or tumour
‣
Internuclear ophthalmoplegia
‣
What is the medial longitudinal fasciculus?
  • Brainstem structure that coordinates abduction of one eye with adduction of the other. This meant it communicates with CN III & VI
‣
How does it present?
  • Impaired adduction of the eye on the side of the lesion
  • Nystagmus in the abducting eye
‣
What are the common causes?
  • MS
  • Brainstem infarction
‣
Bulbar/pseudobulbar palsy
‣
What is the difference between the two?
  • Both are lesions of the corticobulbar tract, affecting cranial nerves 9, 10 & 12 causing impairment of speech & swallow.
  • Bulbar palsy is a LMN lesion of this tract, whereas pseudobulbar palsy is a UMN lesion
‣
What features suggest bulbar palsy?
  • Dysphagia, choking on solids & liquids
  • Quiet nasal speech, drooling and a flaccid fasciculating tongue

‣
What are the causes?
  • MND
  • MG
  • GBS
  • Lateral medullary syndrome (stroke)
‣
What features suggest pseudobulbar palsy?
  • Spastic tongue
  • Slow "hot potato" speech
  • Brisk jaw reflex
  • May have UMN lesion signs in the limbs
‣
Facial nerve palsy
‣
How does Ramsay Hunt present?
  1. Ear pain, HL, vertigo
  2. LMN facial nerve palsy
  3. May have a vesicular rash around ear
‣
Bell's palsy:
‣
How do you manage a presentation if within 72 hours of onset?
  • Prednisolone 60mg/day for 7-10 days
‣
Sensory & motor
‣
Sensory
‣
What are your differentials for peripheral sensory loss?
  • Alcohol
  • B12/folate deficiency
  • CKD / Carcinoma
  • Diabetes mellitus / Drugs (isoniazid, amiodarone, phenytoin, cisplatin)
  • Every vasculitis
    • Cryoglobulinaemia (HepC related), RA, SLE, polyangiitis
‣
What dermatome is affected:
‣
Reduced sensation over the medial side of the thigh, with weakness of knee extension
  • L3
‣
Motor
‣
Motor neuron disease
‣
What mutation is associated with this?
  • SOD1 mutation associated with ALS
‣
What other disease is commonly associated with this?
  • Frontotemporal dementia
‣
What are the 4 types?
  1. Spinal ALS - Classic presentation
  2. Bulbar ALS - Early tongue and bulbar involvement
  3. Progressive muscular atrophy - Only LMN features
  4. Primary lateral sclerosis - Only UMN features
‣
How do you manage this?
  • Riluzole
    • Needs regular monitoring of FBC & LFT
‣
Myasthena gravis
‣
What muscles are commonly affected?
  • Eye lids - Ptosis
  • Eye muscles - Ophthalmoplegia
  • Bulbar muscles - Nasal speech
‣
In a myasthenic crisis, what is important to monitor?
  • FVC
‣
What is this commonly associated with?
  • Thymus hyperplasia / thymoma
‣
How do you investigate for this?
  1. Serum acetylcholine receptor antibody (+ in 80-90%)
    • If negative then test for muscle-specific tyrosine kinase antibodies
  2. CT chest looking for thymic hyperplasia/thymoma
  3. Repeated nerve stimulation (tensilon) → ↓ Action potential
‣
How are they managed?
  • Steroids and anticholinesterase inhibitors (such as pyridostigmine or neostigmine).
  • Severe: IVIG/plasmapheresis
‣
Lambert-Eaton syndrome
‣