Liver Function Tests

LFTs

Hepatocellular damage (hepatitis)

• Aminotransferases (ALT/AST)
• Gamma-Glutamyl transpeptidase (gamma-GT)

Cholestasis (bile ducts)

• Bilirubin
• Alkaline phosphatase
  

Synthetic function

• Albumin
• Prothrombin time

Antibiotics in meningitis

Unknown

• Cefotaxime

Pneumococcus

• Cefotaxime

TB

• Rifampicin
• Isoniazid
• Pyrazinamide
• Ethambutol

Meningococcus

• Benzylpenicillin
• Cefotaxime

Causes of raised serum amylase

Pancreatic

• Acute/chronic pancreatitis
• Pseudocysts
• Carcinoma

Abdominal

• Perforation, duodenal ulcer
• Ectopic pregnancy
• Ovarian tumours

Hepatic

• Gallstones
• Acute hepatitis

Salivary

• Adenitis
• Tumours
• Mumps

Others

• Diabetic ketoacidosis
• Alcohol
• Anorexia
• Burns

Useful terms to describe skin lesions

Atrophy - Thinning of skin
Bulla - Large fluid-filled blister
Crusted - Dried exudate
Ecchymosis - Large 'bruise'
Erosion - Small denuded area of skin
Excoriation - Scratch mark
Fissure - Deep linear crack
Lichenified - Thickened skin with normal markings
Macule - Flat, circumscribed non-palpable lesion
Nodule - Large papule more than 0.5cm
Papule - Small palpable circumscribed lesion
Petechia - Pinpoint-size macule of blood in the skin
Plaque - Large flat-topped palpable lesion
Purpura - Larger macule of blood in the skin which does not blanch on pressure
Pustule - Pus-filled lesion (white/yellow)
Scaly - Visible flakes/ shedding of skin surface
Telangiectasia - Abnormal visible dilatation of blood vessels
Ulcer - Large denuded area of skin
Vesicle - Small fluid-filled blister
Wheal - Raised erythematous swelling (dermal swelling)

Drug and alcohol abuse and dependence

Current evidence suggests that drinking up to 21 units a week (for men) or 14 units a week for women carries no long-term health risk

Alcohol dependence syndrome

Clinical features

• Compulsive need to drink
• Altered alcohol tolerance
• Stereotyped pattern of drinking
• Drinking takes primacy over other activities
• Repeated withdrawal symptoms
• Relief drinking to avoid withdrawal, e.g. early morning drinking
• Rapid relapse if patient drinks again following a period of abstinence

Management

Psychosocial support and group therapy

• Alcoholics Anonymous

Drugs (effects are enhanced by combining them with counselling)

• Naltrexone reduces the risk of relapse into heavy drinking and the frequency of drinking
• Acamprosate alters neurotransmitters and reduces drinking frequency
• Disulfiram (Antabuse) reacts with alcohol to form acetaldehyde which produces unpleasant symptoms to discourage drinking

Drug abuse

• Solvents 'glue sniffing'
• Euphoria
• Floating sensation
• Amnesia
• Visual hallucinations
• Inhalation of vomit
• Bone marrow/brain/liver/kidney toxicity
• Tolerance
• Amphetamines
• Stimulant
• Euphoria
• Psychological dependence
• Restlessness
• Over-activity
• Paranoid psychosis
• Cocaine
• Stimulant
• Hyperarousal
• Dependence
• Paranoid ideation
• Fits
• Coronary artery spasm/disease
• Perforation of nasal septum if inhaled
• Cannabis
• Exaggeration of pre-existing mood
• No definite withdrawal syndrome or tolerance
• Psychosis
• MDMA 'Ecstasy'
• Psychedelic effects
• Hyperpyrexia
• Acute hepatic/renal failure
• Possible chronic brain damage
• Hypnotics (e.g. benzodiazepines)
• Relaxation
• Sleep induction
• Dependence
• Withdrawal syndrome
• Respiratory depression
• Narcotics (morphine, heroin, codeine, methadone, pethidine)
• Calm
• Slight euphoria
• Analgesia
• Flattening of emotions
• Marked and rapid tolerance
• Withdrawal syndrome
• Respiratory depression
• Complications of injecting
• Infection (e.g. HIV/hepatitis B and C/ endocarditis)
• Vein thrombosis

Management

• Withdrawal programmes, e.g. using methadone
• Psychosocial support to help the addict live without drugs

Acute stress reaction and post-traumatic stress disorder

• Occur in individuals in response to exceptional physical or psychological stress

Acute stress reaction

• Lasts a few hours/days
• Initial state of 'daze'
• Then a phase of either
• Withdrawal/stupor or
• Agitation/over-activity
• Commonly associated with autonomic signs of anxiety

Post-traumatic stress disorder

• Delayed/protracted response to a stressful event
• 'Flashbacks'
• Intense distress in/avoidance of situations resembling the event (including anniversaries)
• Emotional blunting/numbness
• Detachment from others
• Hypervigilance
• Insomnia
• Anxiety and depression
• Occasionally suicide

Management

• Counselling

Potassium-sparing diuretics

Amiloride
Spironolactone

Indications

In addition to postassium-wasting diuretics
Chronic heart failure (spironolactone)

• Ascites due to liver disease

Mechanism of action

• Spironolactone inhibits aldosterone
• Amiloride blocks renal sodium uptake

Side effects

• GI disturbance
• Hyperkalaemia
• Hyponatraemia
• Erectile dysfunction
• Gynaecomastia (spironolactone)
• Rash

Cautions/contraindications

• Severe renal impairment
• Hyperkalaemia
• Hyponatraemia

Loop diuretics

Furosemide
Bumetanide

Indications

• Pulmonary oedema
• Chronic heart failure
• Oliguria due to renal failure

Mechanism of action

• Inhibit reabsorption in ascending limb of loop of Henle

Side effects

• Postural hypotension
• Hypokalaemia
• Hyponatraemia
• Gout
• Tinnitus and deafness

Cautions/contraindications

• Anuric renal failure
• Liver failure

Thiazide diuretics

Bendroflumethiazide (bendrofluazide)
Metolazone

Indications

• Hypertension
• Chronic heart failure

Mechanism of action

• Inhibit sodium reabsorption in proximal tubule

Side-effects

• Postural hypotension
• Hypokalaemia
• Hyponatraemia
• Erectile dysfunction
• Gout
• Rash
• Nausea

Cautions/contraindications

• Severe renal impairment
• Hypokalaemia
• Hyponatraemia
• Addison's disease

Proton pump inhibitors

Omeprazole
Lansoprazole

Indications

• Peptic ulcer healing
• Reflux oesophagitis
• H.pylori eradication

Mechanism of action

• Reduce gastric acid secretion by blocking proton pumps

Side-effects

• Diarrhoea 
• Headache
• Rash
• Nausea

Cautions/contraindications

• Liver disease

Interactions

• Omeprazole - Warfarin

Antidotes to common poisons

Iron

• Desferrioxamine - formation of inert complex

Paracetamol

• N-acetylcysteine - accelerates detoxification

Methanol

• Ethanol - competes with metabolic enzymes

Organophosphates 

• Atropine - blocks receptors which mediate toxic effect

Opiates

• Naloxone - drug receptor antagonist

Common important drug interactions

Warfarin

• P450 inhibitors - increased INR bleeding

Theophylline 

• P450 inhibitors - arrhythmias

Digoxin

• Amidarone - arrhythmias
• Verapamil - heart block
• Quinidine - heart block
• Diuretics - heart block

Beta-blockers

• Verapamil - bradycardia
• Diltiazem - asystole

Lithium

• Thiazides - ataxia and fits

Oral contraceptive pill

• Antibiotics - failure of contraception

Azathioprine 

• Allopurinol - bone marrow failure

Platelet disorders

Platelets, derived from megakaryocytes, are involved in the formation of clot

Thrombocytopenia

• Low platelet count
• Low production in bone marrow
• High destruction in circulation
• Causes
• Reduced production
• Leukaemia
• Aplastic anaemia
• Megaloblastic anaemia
• Myeloma
• Immune destruction
• Autoimmune idiopathic thrombocytopenic purpura
• SLE
• Drugs
• Co-trimoxazole
• Coagulation
• DIC
• Haemolytic uraemic syndrome
• Infections
• Viral infection
• Other
• Hypersplenism

Autoimmune thrombocytopenic purpura

• Follows viral infection in children (acute)
• Idiopathic in adult women (chronic)
• 60% have anti-platelet antibodies
• Purpuric rash
• Epistaxis and menorrhagia
• Treat with steroids/splenectomy

Thrombocytosis

• High platelet count
• Haemorrhage
• Inflammation (any site)
• Essential thrombocythaemia

Haematological malignancies

These are malignant proliferations of:

• Lymphocytes
• Hodgkin's disease
• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukaemia
• Myeloma (plasma cells)
• Immature lymphocytes
• Acute lymphoblastic leukaemia
• Hairy cell leukaemia
• Myeloma cells
• Acute myelogenous leukaemia
• Chronic myeloid leukaemia

Lymphomas

Hodgkin's disease

• B or T cell malignant clone

Clinical features

• Lymphadenopathy
• Fever
• Drenching sweats B symptoms
• Weight loss
• Alcohol-induced pain
• Hepatomegaly
• Splenomegaly

Investigations

• Blood count - anaemia
• ESR increased
• Uric acid sometimes increased
• Chest X-ray - mediastinal mass or hilar lymph nodes
• CT scan
• Lymphadenopathy
• Liver or spleen enlargement or infiltration
• Lymph node biopsy and histology
• Bone marrow biopsy (shows Sternberg-Reed cells)

Management

• Depends on
• Stage and histology
• Site of tumour
• Presence of B symptoms
• Radiotherpay
• Chemotherapy
• Myeloablation and stem cell support

Prognosis

• 40-70% survival at 20 years
• Depends on stage of original tumour

Non-Hodgkin's lymphoma

• 70% B cell
• Associated with EBV and HIV infection

Clinical features

• Lymphadenopathy
• Symptoms due to site of tumour
• May involve GI tract, lungs, brain

Investigations

• Blood count
• Anaemia
• Thrombocytopenia
• Liver chemistry
• Chest X-ray
• CT scan of abdomen and thorax
• Bone marrow biopsy
• Lymph node biopsy

Management

• Depends on grade
• Radiotherapy
• Chemotherapy

Burkitt's lymphoma

• Associated with Epstein-Barr virus
• Endemic in West Africa
• Jaw, abdominal and ovarian tumours
• Curable

Acute leukaemias

Epidemiology

• Rare: 5 in 100000

Aetiology

• Unknown in most cases
• T-cell leukaemia - retrovirus (HTLV-1)
• Specific genetic mutations
• Chromosome translocations, e.g. t (15;17)
• Environment factors
• Ionizing radiation

Clinical features

• Bone marrow failure
• Weakness and tiredness due to anaemia
• Bruising due to thrombocytopenia
• Repeated infections

Investigations

• Blood count
• Blood film - leukaemic blast cells
• Bone marrow - blast cells

Management

• Correct anaemia and thrombocytopenia
• Treat any infection
• Chemotherapy to achieve remission
• Myeloablation with stem cell support to clear marrow of malignant cells

Acute myeloid leukaemia (AML)

• Classified by cell type
• 70% alive at 1 year -> 30% alive at 5 years
• Treatment aims for complete remission
• Followed by bone marrow ablation

Acute lymphoblastic leukaemia (ALL)

• Predominantly a disease of children
• Cure rate 50-60% in children, 30% in adults
• Central nervous system involvement common
• Prophylactic intrathecal chemotherapy

Chronic leukaemia

• Chronic leukaemias occur in older patients, most of whom die within 5 years of the diagnosis
• Clinical course consists of a chronic illness lasting 3-4 years, followed by transformation into an acute leukaemia or sometimes myelofibrosis in the case of chronic myeloid leukaemia

Chronic myeloid leumaemia (CML)

Clinical features

• Anaemia
• Night sweats and fever
• Weight loss
• Splenomegaly -> pain

Investigations

• Blood count - raised white count
• Multiple myeloid precursors
• Bone marrow biopsy
• Genetic testing for the Philadelphia chromosome (9:22 translocation) (positive in 90-95%)

Management

• Interferons -> remissions in 10%
• Hydroxyurea reduces white cell count
• Myeloablation with bone marrow transplant

Chronic lymphocytic leukaemia (CLL)

Clinical features

• Often an incidental finding
• Infections due to neutropenia
• Anaemia (may be due to haemolysis)
• Lymphadenopathy
• Hepatosplenomegaly

Investigations

• Haemoglobin low or normal
• White count > 15 x 10^9 / L
• 40% lymphocytes
• Platelets low or normal
• Serum immunoglobulins may be low

Management

• Nothing if asymptomatic
• Steroids for haemolysis
• Fludarabine or chlorambucil

Hairy cell leukaemia

• Rare
• Usually a B cell tumour
• Cells have filament-like projections

Myeloproliferative disorders

• Uncontrolled proliferation of a blood cell line
• Can transform into acute leukaemias or from myeloproliferation to another

Polycythaemia vera

• Red cell proliferation
• Patients usually >60 years old

Clinical features

• Tiredness
• Depression
• Tinnitus
• Vertigo
• Visual disturbance
• Itching after a hot bath
• Gout (due to increased cell turnover)
• Thrombosis or haemorrhage
• Plethora and cyanosis
• Splenomegaly

Investigations

• Haemoglobin raised
• Packed cell volume (haematocrit) increased
• 50% have increased platelets
• 75% have increased white cells
• Uric acid increased
• Leucocyte alkaline phosphatase increased

Management

• Venesection
• Chemotherapy
• Allopurinol to avoid gout

Prognosis

• 30% -> myelofibrosis
• 5% -> AML

Essential thrombocythaemia

• Platelet count > 1000 x 10^9 / L
• Bruising and bleeding (poor platelet function)
• Increased risk of thrombosis

Myelofibrosis

• Stem cell proliferation
• Bone marrow fibrosis

Clinical features

• Anaemia
• Weight loss
• Splenomegaly
• Bone pain
• Gout

Investigations

• Anaemia
• High platelets
• 'Dry' bone marrow aspirate
• High uric acid

Management

• Blood transfusion
• Folic acid
• Chemotherapy and radiotherapy
• Splenectomy may be required

Prognosis

• 10-20% -> AML

Myelodysplasia

• Stem cell defects
• Bone marrow failure
• Abnormal red cells, leucocytes and platelets

Management

• Supportive therapy
• Low-intensity chemotherapy

Multiple myeloma and hyperglobulinaemia

• Clonal expansion of plasma cells resulting in very high production of a single immunoglobulin (paraprotein) or an immunoglobulin component

Myeloma

• Elderly patients

Clinical features

• Bone lesions -> pain and fractures
• Hypercalcaemia
• Bone marrow infiltration
• Anaemia, neutropenia
• Renal impairment
• Hyperviscosity syndrome

Investigations

• Blood count (anaemia, low white cells)
• Elevated ESR and CRP
• Elevated calcium, urea, and creatinine
• Protein electrophoresis - monoclonal band
• Skeletal X-ray survey - lytic lesions, e.g. skull
• 24-hour urine for light chain proteins
• Bone marrow aspirate - plasma cells

Management

• Supportive treatment
• Steroids and radiotherapy for bone lesions
• Chemotherapy

Waldenstrom's macroglobulinaemia

• Older males
• IgM paraprotein
• Hyperviscosity syndrome
• Lymphadenopathy
• Malaise and weight loss

Complications of hyperviscosity syndrome

• Headaches
• Visual disturbance - retinal artery and vein occlusion
• Cerebrovascular accidents - indication for urgent plasmapheresis
• Thrombophilia

Hypopituitarism

Aetiology

• Congenital
• Kallmann's syndrome
• Infective
• Basal meningitis
• Encephalitis
• Syphilis
• Vascular
• Sheehan's syndrome
• Tumours
• Pituitary
• Hypothalamic
• Craniopharyngioma
• Meningioma
• Glioma
• Metastases (especially breast)
• Lymphoma
• Infiltration
• Sarcoidosis
• Langerhan's histiocytosis
• Haemochromatosis
• Others
• Radiation
• Anorexia nervosa
• Trauma or previous surgery

Clinical features

• Due to progressive loss of anterior pituitary hormones (listed in order of frequency)
• Growth hormone
• Growth failure
• Short stature
• Prolactin
• Failure of lactation
• Gonadotrophins
• Delayed puberty
• Infertility
• Amenorrhoea
• Loss of body hair
• TSH
• Hypothyroidism
• ACTH
• Adrenal failure (without pigmentation)

Investigations

• Determine hormone deficiencies
• Pituitary imaging, e.g. CT scan, MRI scan

Management

• Treat cause
• Hormone replacement

Fulminant hepatic failure

Aetiology

• Hepatitis A/D/E
• Drugs
• Paracetamol
• Volatile liquid anaesthetics
• Isoniazid
• Ecstasy
• Wilson's disease
• Pregnancy
• Reye's syndrome

Clinical features

• Jaundice
• Encephalopathy
• Drowsiness -> coma
• Hypoglycaemia
• Low potassium or calcium
• Haemorrhage

Management

• Treat on a specialist unit
• Supportive therapy
• Liver therapy

Autoimmune hepatitis

Epidemiology

• Female > Male
• Associated with other autoimmune disease

Clinical features

• May be asymptomatic
• Jaundice
• Bruising
• Signs of acute or chronic liver disease

Investigations

• Antinuclear antibodies (Type 1)
• Anti-smooth muscle antibodies (Type 1)
• Antimitochondrial antibodies (Type 1)
• Anti-liver/kidney microsomal antibodies (Type 2)
• Anti-liver cytosol antibodies (Type 2)

Management

• Steroids/azathioprine

Pulmonary embolism

Obstruction of a branch of the pulmonary artery by clot from a DVT


Clinical features

• Small or medium PE
• Pleuritic chest pain
• Shortness of breath
• Haemoptysis in 30%
• Tachypnoea
• Pleural rub
• Coarse crackles
• Pleural effusion
• Massive PE
• Collapse
• Shock
• Cardiac arrest electromechanical dissociation
• Elevated JVP ('a' wave)
• Gallop rhythm
• Recurrent PE
• Breathlessness
• Weakness
• Syncope
• Gradual deterioration

Investigation

• Chest X-ray - oligaemic area
• ECG
• S wave in lead I, Q wave and invested T in lead III
• Right axis deviation
• Right bundle branch block
• Fibrin degredation products (FDPs) and D-dimer in blood are elevated
• V/Q scan
• Radionucleotide scan
• Demonstrates defects in perfusion of the lung in areas with normal ventilation
• Blood gases - hypoxia and low PaCO2
• Echcardiogram - high PA pressure
• Pulmonary angiography / CT pulmonary angiogram

Management

• High-flow oxygen
• Analgesia
• Intravenous heparin or
• Low molecular weight heparin
• Consider thrombolysis (rtPa)

Deep Vein Thrombosis (DVT)

Formation of thrombus in

• Deep calf vein
• Axillary vein

Clinical features

• Pain and tenderness
• Swelling of the limb
• Redness of overlying
• Pulmonary embolism

Investigations

• Doppler ultrasound of the vein
• Venography (intravenous contrast)

Management

• Low molecular weight heparin or
• Intravenous heparin
• Warfarin
• Bed rest
• Graduated pressure stocking

Complications

• Phlebitis
• Venous eczema

Leg Ulcers

Aetiology

• Venous hypertension
• Arterial insufficiency
• Neuropathic (e.g. diabetes mellitus)
• Neoplastic (e.g. squamous cell carcinoma)
• Vasculitis
• Infection, e.g. syphilis
• Blood disorders, e.g. sickle cell disease
• Trauma

Venous ulcers

• Most common cause
• Associated with venous hypertension or previous thrombosis
• Often recurrent and chronic
• Usually painless
• Medial aspect of leg
• Exclude arterial insufficiency with Doppler

Management

• Topical therapy to ulcer
• Compression bandaging and elevation of legs
• Antibiotics for overt infection
• Diuretics for oedema
• Analgesia if painful
• Skin grafting if resistant to therapy

Arterial ulcers

• Punched out
• Painful
• Leg cold and pale
• Absent pulses
• History of hypertension, claudication, smoking, angina
• Investigate with Doppler studies/angiogram

Management

• Analgesia
• Topical treatment of ulcer
• Vascular reconstruction

Neuropathic ulcer

• Over pressure areas, e.g. metatarsal heads
• Result of trauma
• Polyneuropathy, e.g. diabetes mellitus
• Painless

Management

• Keep clean
• Avoid trauma including good foot care

Psoriasis

Common disorder characterised by red scaly plaque

Epidemiology

• 2% of the population
• Males = Females

Aetiology

• T lymphocyte - driven
• Genetic - polygenic
• Environmental triggers
• Infection
• Drugs, e.g. lithium
• UV light
• Alcohol
• Stress/anxiety

Clinical features

Chronic plaque psoriasis

• Purplish/red scaly plaques, particularly on extensor surfaces
• Scalp frequently involved
• Can occur in areas of skin trauma (Kobner phenomenon)
• 50% associated with nail changes
• Nail pitting
• Distal separation of nail plate (onycholysis)
• Yellow/brown discolouration
• Subungual hyperkeratosis
• If severe, loss of nail plate

Flexural psoriasis

• Occurs in older patients
• Patches
• Groin
• Natal cleft
• Submammary areas

Guttate psoriasis

• Raindrop-like lesions on trunk
• Occurs in children/young adults 2 weeks after a streptococcal sore throat

Arthritis associated with psoriasis

• Bilateral
• DIP joints and PIP joints

Management

• Education and explanation
• Avoid irritants
• Topical steroids
• Calcipotriol (Vitamin D3 analogue)
• Coal tar
• Phototherapy (e.g. PUVA (psoralen + UVA))
• Methotrexate if severe

Complications

Erythroderma

• Widespread inflammation of the skin

Common causes

• Atopic eczema
• Psoriasis
• Drugs, e.g. sulphonamides, gold
• Seborrhoeic dermatitis

Management

• Bed rest
• Liberal IV fluids
• Keep warm
• Emollients
• Beware of sepsis
• Treat/remove the cause

Complications

• High-output cardiac failure
• Hypothermia
• Dehydration
• Hypoalbuminaemia
• Increased basal metabolic rate
• Capillary leak syndrome

Eczema (Dermatitis)

Acute - inflamed, weeping skin with vesicles
Subacute - erythema, dry/flaky skin, crusted
Chronic - lichenified skin


Epidemiology

• 40% of population have an episode associated with atopy
• Atopic individuals have a tendency to
• Asthma
• Eczema
• Hay fever
• Allergic rhinitis

Aetiology

• Genetic-polygenic
• Environmental triggers
• Detergents/chemicals
• Infection
• Stress/anxiety
• Animal fur
• Foods (dairy products in the very young)

Clinical features

• Itchy erythematous scaly patches
• Often flexural
• May be associated with nail pitting

Investigations

• May have raised IgE or eosinophils
• Skin-patch testing

Management

• Education and explanation
• Avoid irritants
• Emollients, bath oil or soap substitutes
• Topical steroids or immunomodulators (tacrolimus)
• Antibiotics for secondary infection
• Antihistamines
• Second-line agents
• Ultraviolet (UV) light
• Oral steroids
• Ciclosporin/azathioprine

Multiple Sclerosis

Multiple plaques of demyelination in the brain and spinal cord disseminated in time and place

Clinical diagnosis: two neurological events separated in time and neurological location

Prevalence

• Increases moving north from the Equator
• 60-100/100000 in the UK

Aetiology

• Increased concordance among monozygotic twins
• HLA haplotype A3, B7, D2 and DR2 is more common

Environmental

• ?Viral infection
• ?Dietary antigens

Pathology

• Plaques of demyelination particularly in
• Optic nerves
• Periventricular region
• Brainstem and cerebellar connections
• Cervical spinal cord
• Corticospinal tracts
• Posterior columns

Clinical patterns

• Relapsing/remitting
• Chronic progressive

Investigation

• Imaging
• MRI brain and spinal cord (visualises multiple plaques)
• CSF
• Oligoclonal bands in 80%
• Raised mononuclear cell count 5-60 cells/mm^3
• Visual evoked responses
• Delayed following optic neuropathy

Management

• No treatment has been shown to alter long-term outcome
• Corticosteroids - I.V. methylprednisolone or ACTH may speed recovery in acute relapses
• Beta-interferon - reduces relapse rate but not long-term outcome
• Physiotherapy
• Occupational therapy
• Walking aids
• Wheelchairs
• Car/house conversions
• Speech therapy
• Counselling

Prognosis

• Unpredictable course ranging from grave disability to mind and benign

Hepatic enzyme inducers and Hepatic enzyme inhibitors

Hepatic enzyme inducers

• Decrease the bioavailability of other drugs that are metabolised by those enzymes
• Increase the bioavailability of other drugs that require metabolism for their activation
• Examples include:
• Long term alcohol abuse
• Rifampicin
• Anticonvulsants: phenytoin, carbamazepine, phenobarbitone, primidone
• Spironolactone
• Griseofulvin

Hepatic enzyme inhibitors

• Increase the bioavailability of other drugs that are metabolised by those enzymes
• Decrease the bioavailability of other drugs that require metabolism for their activation
• Examples include:
• Alcohol consumed during 'binges'
• Antibiotics
• Isoniazid
• Erythromycin
• Sulphonamides
• Metronidazole
• Chloramphenicol
• Ketoconazole
• Anticonvulsants
• Valproate
• Cimetidine
• Allopurinol
• Chlorpromazine
• Imipramine
• Propranolol
• Metoprolol
• Interferon

Causes of myopathies

• Inflammatory
• Polymyositis
• Metabolic
• Cushing's syndrome
• Myasthenic
• Myasthenia gravis
• Hereditary
• Duchenne muscular dystrophy
• Myotonias
• Myotonic dystrophy
• Channelopathies
• Periodic paralysis

Dystrophia myotonica

Autosomal dominant inheritance

Clinical features

• Cataracts
• Frontal baldness
• Ptosis
• Facial weakness
• Progressive distal muscle weakness
• Mild intellectual impairment
• Cardiomyopathy
• Hypogonadism
• Glucose intolerance

Lambert-Eaton myasthenic-myopathic syndrome

Non-metastatic manifestation of small cell carcinoma of the bronchus due to defective acetylcholine release at the neuromuscular junction


Clinical features

• Muscle weakness and absent reflexes which improve with contraction

CHADS2 and CHA2DS2-VASc

CHADS2

• Congestive heart disease (Heart failure or ejection fraction less than or = 35%)
• Hypertension
• Age (> or = 75 years old)
• Diabetes mellitus
• Previous Stroke/TIA or systemic emboli - 2 points

0 = 1.9% stroke risk
6 = 18.2% stroke risk

CHA2DS2-VASc

• Congestive heart disease (Heart failure or ejection fraction less than or = 35%)
• Hypertension
• Age (> or = 65 years old) - up to 2 points (1 for 65-74 and 2 or 75 and above)
• Diabetes mellitus
• Previous Stroke/TIA or systemic emboli - 2 points
• Vascular disease (previous MI, peripheral arterial disease or aortic plaque)
• Female gender

0 points 0% stroke risk (??)
9 points 15.2% stroke risk

Systemic sclerosis

A multisystem disease with widespread obliterative damage to small blood vessels associated with fibosis of the skin and internal organs

Clinical features

Raynaud's phenomenon

• 97% of cases
• Arterial spasm of hands and feet
• Three phases
• Pallor
• Cyanosis
• Erythema
• Numbness and pain

Skin

• Hands, face, feet, foearms
• Tight, waxy and tethered
• 'Beaking of nose'
• Microstomia
• Digital ulcers
• Telangiectasia
• Nasal fold capillary loops

GI tract

• Oesophagus
• Reflux
• Poor motility
• Dilatation
• Small bowel
• Bacterial overgrowth
• Malabsorption
• Renal
• Renal failure
• Malignant hypertension
• Cardiorespiratory system
• Pulmonary fibrosis (common cause of death)
• Primary or secondary pulmonary hypertension
• Arrhythmias
• Conduction defects
• Pericarditis

CREST syndrome

• Calcinosis (calcium deposis in skin and elsewhere)
• Raynaud's phenomenon
• oEsophageal dysmotility
• Sclerodactyly
• Telangiectasia

Investigations

• Normocytic, normochromic anaemia
• Urea and electrolytes and urinalysis including creatinine clearance
• Autoantibodies
• Speckled/nucleolar/anticentromere - 70-80%
• Rheumatoid factor - 30%
• Chest X-ray - reticulonodular shadowing
• Other tests according to organ involved

Management

• Education, counselling and family support
• Hand-warmers and vasodilators for Raynaud's
• Proton pump inhibitos and motility agents
• Antibiotics and nutritional supplements
• Antihypertensives
• I.v. prostacyclin

MCQ revision - Liver metastases from colorectal carcinoma

• 50% of patients with colorectal carcinoma will develop liver metastases
• The median survival with liver metastases is 1 year
• Criteria for resection
• Less than 3 metastases
• Single lobe involvement
• At least 20% of the liver must be spared
• No evidence of IVC invasion
• Hepatic resection is a potentially curative procedure
• Radiofrequency ablation is not curative but is an alternative to surgically non-resectable metastases. It can get rid of up to 90% of metastases. 

Huntington's disease

Inherited progressive chorea and dementia in middle life (CAG repeats)

Prevalence

• 5:100000

Aetiology

• Autosomal dominance with full penetrance
• Children of an affected parent have a 50% chance of inheriting the mutation on chromosome 4

Pathology

• Cerebral atrophy
• Loss of neurones in caudate nucleus and putamen
• Depletion of gamma-aminobutyric (GABA), angiotensin-converting enzyme (ACE) and met-enkephalin in substantia nigra

Clinical features

• Chorea (Sudden involuntary jerky semi-purposeful movements, flitting from one part of the body to another)
• Progressive dementia

Investigations

• MRI or CT shows atrophy or caudate nucleus

Management

• Phenothiazines may reduce chorea

Prognosis

• Death 10-20 years after onset

Screening

• Mutation analysis is available for presymptomatic screening in families but no effective treamtent is known to alter disease progression

Other causes of chorea

• Sydenham's chorea (rheumatic fever)
• Drugs, e.g. phenytoin
• Thyrotoxicosis
• Stroke
• Systemic lupus erythematosus (SLE)

Diabetes Insipidus

Deficiency of anti-diuretic hormone (ADH) or insensitivity to its action

Aetiology

• Cranial causes
• Idiopathic
• Familial (DIDMOAD - Diabetes insipidus, diabetes mellitus, optic atrophy, deafness)
• Tumours, e.g. craniopharyngioma, glioma, metastases (breast)
• Infiltration, e.g. sarcoidosis, histiocyosis
• Sheehan's syndrome (pituitary infarction following post- or antepartum haemorrhage)
• Nephrogenic causes
• Idiopathic
• Renal tubular acidosis
• Hypokalaemia
• Hypercalcaemia
• Drugs, e.g. lithium, demeclocycline, glibenclamide

Clinical features

• Polyuria urine output (10-15L/day)
• Thirst
• Nocturia
• Polydipsia
• Dehydration

Differential diagnosis

• Primary polydipsia (excessive water drinking/ normal ADH secretion)

Investigations

• Cranial diabetes insipidus
• ADH decrease
• Water deprivation test
• High plasma osmolality
• Low urine osmolality
• Normal response to DDAVP
• Nephrogenic diabetes insipidus
• ADH increase
• Water deprivation test
• High plasma osmolality
• Low urine osmolality
• No response to DDAVP
• Inappropriate ADH
• ADH increase
• Plasma osmolality low
• Urine osmolality high

Management

• Treat underlying cause
• Synthetic vasopressin analogue
• DDAVP (Desmopressin)
• Carbamazepine
• Chlorpropamide

Jaundice - Once and for all

Logic

Pre-hepatic

• Increased quantity of bilirubin
• Decreased transport to the liver

Intra-hepatic

• Defective uptake
• Defective conjugation
• Defective excretion of bilirubin by liver cells

Post-hepatic

• Defective transport of conjugated bilirubin by the biliary duct system

 

 

Causes

 

Pre-hepatic

• Haemolysis
• Hereditary spherocytosis
• Haemolytic anaemia
• Pernicious anaemia
• Incompatible blood transfusion

 

Intra-hepatic

• Hepatitis and intra-hepatic cholestasis
• Hepatitis
• Cirrhosis
• Drugs
• Toxins
• Genetic condition (Gilbert's etc.)
• Liver tumour (primary or secondary)

 

Post-hepatic

• Obstructive
• Obstruction in the lumen (gallstone)
• Obstruction in the wall (atresia, stricture, chronic cholangitis, tumour of bile duct)
• External compression (pancreatitis, tumour, pancreatic cysts)

 

 

Deranged LFTs
 
Pre-hepatic
• Bilirubin increased (1)
• Everything else normal
 
 
Hepatitis
• Bilirubin increased (2)
• Alk phosphatase normal/increased
• ALT/AST increased (2)
• Gamma GT increased (2)
• PT (INR) normal

 

Cirrhosis
• Bilirubin increased (1)
• Alk phosphatase normal/increased
• ALT/AST normal/increased
• Gamma GT normal/increased
• PT (INR) increased

 

Obstruction
• Bilirubin increased (2)
• Alkaline phosphatase increased (2)
• ALT/AST normal/increased
• Gamma GT increased (2)
• PT (INR) normal

 

 

Clinical manifestation

 

Pre-hepatic

• Jaundice
• Mild
• Unconjugated bilirubin
• Bilirubin rarely >100 mmol/litre
• Urine
• Normal colour
• Stool
• Normal colour
 

 

Intra-hepatic

• Jaundice
• Variable
• Bile may be conjugated or unconjugated
• Urine
• Dark
 
• Stool
• Normal colour

 

Post-hepatic

• Jaundice
• Variable
• Conjugated bilirubin
• Bilirubin may be >1000 mmol/litre
• Urine
• Dark
• Stool
• Pale

Acute Nephritic Syndrome

Comprises

• Haematuria
• Proteinuria
• Hypertension
• Oedema
• Oliguria
• Uraemia

Aetiology

• Streptococcal throat infection or otitis media
• Systemic vasculitis
• Cryoglobulinaemia

Investigations

• General
• Urine microscopy for red cells and casts
• Serum urea and creatinine (raised)
• Creatinine clearance (low)
• 24 hour urine protein (raised)
• C3 and C4 (low)
• Chest X-ray for pulmonary oedema
• Renal imaging (usually normal)
• Diagnostic
• Throat swab
• Antistreptolysin O titre
• ANCA
• Anti-GBM antibody
• Cryoglobulins

Management

• Daily weight checks
• Fluid balance chart
• Antihypertensive
• BP monitoring
• Salt restriction
• Fluid restriction
• Diuretics
• Dialysis if needed
• Antibiotics for post-streptococcal infections

Glomerulonephritis - general

• A group of disorders
• With immunologically mediated injury to glomerulus
• Involving both kidneys
• With secondary injury after initial immune insult
• May be part of generalised disease
• Classified by histology

Pathogenesis

• Deposition of immune complexes
• Deposition of anti-glomerular basement membrane (anti-GBM) antibody

Aetiology

• Immune complex nephritis
• Unknown antigen
• Viruses
• Mumps
• Measles
• Hepatitis B and C
• Epstein-Barr virus (EBV)
• Coxsackie
• Varicella
• HIV
• Bacteria
• Group A Beta-haemolytic streptococci
• Streptococcus viridans
• Staphylococci
• Treponema pallidum
• Gonococci
• Salmonellae
• Parasites
• Plasmodium malariae
• Schistosoma
• Filiariasis
• Host antigens
• DNA (systemic lupus erythematosus - SLE)
• Cryoglobulins
• Malignant tumours
• Drugs
• Penicillamine
• Anti-GBM antibody
• Antibodies to type IV collagen
• Secondary mechanisms
• Complement activation
• Fibrin deposition
• Platelet aggregation
• Neutrophil-driven inflammation
• Kinin activation
• Clinical features
• GN presents in one of four ways
• Asymptomatic proteinuria +/- microscopic haematuria
• Acute nephritic syndrome
• Nephrotic syndrome
• Chronic renal failure

Investigations

• 24 hour urinary protein (measure twice)
• Urine microscopy
• Renal function
• Auto antibodies
• Renal biopsy

Examining the Renal System

All systems need to be examined but pay special attention to the following

Palpation of kidneys

• Place one hand posteriorly on the flank with the other hand anteriorly
• Gently push up from below aiming to 'ballot' the kidney
• Differences between kidney and spleen
• Kidneys are ballotable
• Spleen has a notch
• You cannot get above the spleen
• Spleen is dull to percussion

Kidneys

• Position
• Size
• Shape
• Scars from previous surgery

Urine

• Urinalysis
• Chemical (Stix) testing
• Blood
• Protein
• Glucose
• Bacterial nitrites
• Urinary pH
• Specific gravity and osmolality
• Microscopy
• White cells
• Red cells
• Bacteria
• Casts
• Volume
• Oliguria
• Polyuria

Function of kidneys

• Excretory
• Waste products
• Regulatory
• Control of body fluid volume and composition
• Endocrine
• Erythropoietin
• Renin-angiotensin
• Prostaglandins
• Metabolic
• Vitamin D

Neurology - Revision Boxes (Ultimate Revision)

Headache: classic presentation

• Tension headache
• Stress, tight band around head
• Subarachoid haemorrhage
• Sudden onset, 'kicked in back of head'; associated with vomiting
• Migraine
• Unilateral 'throbbing', aura, vomiting, photophobia
• Giant-cell arteritis
• Tender pulseless temporal arteries; jaw claudication
• Mass lesion
• Pain worse on coughing/sneezing
• Confusion
• Seizures
• Localising focal neurology
• Signs of intracranial pressure, e.g. papilloedema
• Benign intracranial hypertension
• Usually obese young woman; increased CSF (cerebrospinal fluid) pressure but no mass lesion
• Meningitis
• Fever, neck stiffness, photophobia, rash
• Subdural haemorrhage
• Head injury, chronic course, fluctuating consciousness

Distinguishing UMN and LMN lesions

UMN

• Involves corticospinal tract
• Weakness in upper limb extensors, lower limb flexors (pyramidal distribution)
• Increased tone
• Hyperreflexia, clonus
• Pronator drift
• Loss of abdominal reflexes
• Extensor plantar response

LMN

• Lesion at level of anterior horn cell or distal to it
• Fasciculation and wasting
• Loss of reflexes
• Hypotonia

Neurological disease

• Motor neuron disease
• Mixed UMN and LMN signs
• NO sensory loss
• Multiple sclerosis
• Optic neuritis is a common finding in EMQs
• Non-specific signs, e.g. leg weakness, ataxia
• May mention heat worsens symptoms (increases CSF protein, oligoclonal IgG bands on electrophoresis)
• Delayed visual/somatosensory evoked potential
• Parkinson's disease
• TRAP - Tremor, Rigidity, Akinesia, Postural hypotension
• Lead-pipe rigidity, cog-wheel rigidity (if tremor)
• Pill rolling tremor
• Festinant gait with poor arm swing
• Myasthenia gravis
• Young woman presents with weakness of muscles
• On examination: bilateral ptosis, proximal muscle weakness
• Electromyography (EMG): decreased muscle action potential after continuous simulation
• Serum acetylcholine receptor antibodies
• Huntington's disease
• Onset of chorea in middle age, dementia later
• Positive family history (autosomal dominant)
• Normal pressure hydrocephalus
• Triad of gait apraxia, confusion and incontinence

Features of eponymous syndromes

• Cauda equina syndrome
• Saddle anaesthesia
• Bowel/bladder disturbance
• Bilateral pain legs
• Brown-Sequard syndrome
• Ipsilateral pyramidal signs
• Contralateral loss of pain and temperature
• Guillain-Barre syndrome
• Ascending symmetrical flaccid muscle weakness preceding recently respiratory/gastrointestinal infection
• Shy-Drager syndrome
• Combination of parkinsonism plus primary autonomic failure, e.g. postural hypotension
• Wernicke's encephalopathy
• Triad of
• Nystagmus
• Ophthalmoplegia
• Ataxia
• Caused by thiamine (vitamin B1) deficiency
• Reversible but if untreated develops to Korsakoff's syndrom
• Korsakoff's syndrome
• Signs of gross defect in memory of recent events
• Confabulation may be present
• Condition is irreversible

Gait and different conditions

• Parkinson's disease
• Shuffling, festinant gait
• Sensory ataxia, e.g. peripheral neuropathy
• High-stepping/stamping gait
• Spastic paraplegia
• Scissor gait
• Cerebellar lesion
• Wide-based gait
• Cerebrovascular disease (marche a la petit pas)
• Shuffling small steps

Symptoms/signs of nerve root innervation

Reflex

• C5-C6 supinator
• C5-C6 biceps
• C7 triceps
• L3-L4 knee
• S1 ankle

OR

• S1,S2 ankle
• L3,L4 knee
• C5,C6 biceps
• C7,C8 triceps
• 1,2,3,4,5,6,7,8 :)

Movements

• C5 shoulder abduction
• C5,C6 elbow flexion
• C7 elbow extension
• T1 finger abduction
• L1, L2 hip flexion
• L3, L4 knee extension
• L4, L5 dorsiflex ankle
• L5-S1 hip extension
• S1 knee flexion, plantar flexion and eversion ankle

The pupil in neurological problems

• Bilateral dilated pupils
• Plus no vestibulo-ocular reflexes = Brain stem death
• Plus euphoric = Amphetamines, cocaine
• Plus anticholinergic signs, e.g. increased pulse, decreased BP, urinary retention = Tricyclic antidepressant overdose
• Bilateral, pinpoint pupils
• With respiratory depression = Opiate overdose
• Dilated pupil:
• Ptosis, eye deviated laterally and downwards = Nerve III lesion
• Irregular, reacts poorly to light and accommodation = Myotonic pupil
• Usually young woman may have reduced tendon reflexes = Holmes Adie pupil
• Constricted pupil:
• Irregular pupils, reacts to accommodation but not light (known as Argyll Robertson pupil) = Neurosyphilis
• Unilateral ptosis, loss of sweating on same side of face (anhidrosis) = Horner's syndrome

Limited movements and visual field defects

Limited movements

• Defective elevation, depression, adduction = Nerve III lesion
• Defective depression in adduction, vertical diplopia worse in downgaze = Nerve IV lesion
• Failure to abduct, horizontal diplopia worse on abduction = Nerve VI lesion

Visual field defects

• Bitemporal hemianopia
• Chiasma lesion (e.g. pituitary tumour)
• Superior quadrantanopia
• Temporal lobe lesion
• Inferior quadrantanopia
• Parietal lobe lesion
• Homonymous hemianopia
• Optic radiation, visual cortex injury
• Central scotoma
• Macula (e.g. degeneration/oedema)

Nerve injury

• Median nerve C6-T1
• Wasting thenar eminence
• Loss of sensation on lateral palmar surface of three and a half digits
• Test for weakness in abductor pollicis brevis
• Frequently affected in carpal tunnel syndrome
• LOAF
• Lateral 2 lumbricals
• Opponens pollicis
• Abductor pollicis brevis
• Flexor pollicis brevis
• Ulnar nerve C8-T1
• Wasting of hypothenar eminence
• Sensory loss over medial one and a half fingers
• Test for weakness of abductor digiti minimi
• 'Claw hand' deformity
• MAFIA
• Medial 2 lumbricals
• Adductor pollicis
• First dorsal interossei
• Interossei
• Abductor digiti minimi
• Radial nerve C5-T1
• Weakness of wrist extension, leading to 'wrist drop'
• Anaesthesia over first dorsal interosseous muscle
• BESTS
• Brachioradialis
• Extensors of the wrist
• Supinator
• Triceps
• Sensation over anatomical snuffbox
• Common peroneal nerve L4-S1
• Weakness in dorsiflexion and eversion of foot
• Sensory loss over dorsum of foot
• Tibial nerve L4-S3
• Inability to invert foot or stand on tip-toe
• Sensory loss over sole of foot
• Klumpke's palsy C8-T1
• paralysis of intrinsic muscles of the hand
• Loss of sensation in ulnar distribution
• Horner's syndrome sometimes present
• Erb's palsy C5-C6
• Loss of shoulder abduction and elbow flexion
• Arm held internally rotated
• 'Waiter's tip' sign if arm adducted behind back

Stroke: Signs and symptoms

• Anterior circulation stroke
• Unilateral weakness/sensory deficit
• Homonymous hemianopia
• High cerebral dysfunction, e.g. dysphasia, neglect
• Posterior circulation stroke
• Cranial nerve palsies/cerebellar signs, e.g. vertigo, dysarthria, ataxia, choking
• Isolated homonymous hemianopia
• Site: dominant frontal lobe (Broca's area). Broca's (expressive) dysphasia
• Patient can understand you but replies in non-fluent speech
• Site: dominant temporoparietal lobe. Wernicke's (receptive) dysphasia. Site: PICA thrombosis. Lateral medullary syndrome
• Patient has impaired comprehension
• Speech fluent but jargon
• Patient has symptoms of
• Vertigo
• Vomiting
• Dysphagia
• Ipsilateral signs can include
• Ataxia
• Horner's syndrome
• Nerve V, VI palsy
• Contralateral signs include loss of pain, temperature and sensation in face

Quick revision of carpal bones

She - Scaphoid
Looks - Lunate
Too - Triquetrum
Pretty - Pisiform
Try - Trapezium
To - Trapezoid
Chase - Capitate
Her - Hamate

EMQ practice - Cranial nerve lesions

• 55 Year old, Male, Unilateral weakness, Wasting, Fasiculation of the tongue, Tongue deviates to the left on protrusion
• Left CN 12 lesion
• Tongue deviates to the side of the lesion
• 44 Year old, Male, Progressive perceptive deafness, Vertigo, Unilateral facial weakness, Loss of sensation on that side of the face, Imaging reveals presence of a cerebellopontine tumour
• CN5, 7 and 8 lesion
• Cerebellopontine tumours often present clinically as a result of impingement on cranial nerves in the cerebellopontine angle
• Hoarse voice, Difficulty in swallowing and choking while drinking fluids, Visible weakness of elevation of the palate, Depression of palatal sensation and loss of gag reflex
• CN9, 10 lesion
• Cranial nerve IX and X lesions rarely occur in isolation and can also accompany nerve XI and XII lesions after infarction in the brain stem or as a result of pathology around the jugular foramen
• 28 Year old, Male, Surgery, inability to rotate the head to the right and shrug the left shoulder
• Left CN11 lesion
• Accessory nerve is the motor supply to the trapezius and sternocleidomastoid. The latter muscle allows rotation of the head to the opposite side
• 35 Year old, Female, Multiple sclerosis, Diplopia, Inability to abduct pupil on one side
• CN6 lesion
• Diplopia in multiple sclerosis can result from demyelination of cranial nerves associated with eye movements, i.e. III, IV, and VI

Seronegative spondyloarthropathies

• Conditions affecting the spine and peripheral joints which cluster in families and are associated with HLA-B27

Ankylosing spondylitis

• Episodic inflammation of the spine and sacroiliac joints
• Asymmetrical large joint arthritis
• HLA-B27 in >90%
• Associated with uveitis and costochondritis
• Inflammatory markers elevated
• X-rays
• Erosions and sclerosis of affected joints
• Syndesmophytes
• Bamboo spine
• Treated with preventative exercises and NSAIDs, TNF-alpha blocking drugs if severe
• Infliximab and etanercept

Psoriatic arthritis

Clinical features

• Arthritis in association with psoriasis
• May predate skin lesions
• DIP most common joints affected
• Dactylitis
• Erosions on X-rays (centre of joint unlike juxta-articular erosions in RA)
• 5% have arthritis mutilans
• Nail dystrophy in 85% of cases
• HLA-B27 in 50%

Management

• Treated with
• NSAIDs
• Steroid injections to joints
• Sulfasalazine
• Methotrexate/ciclosporin
• TNF-alpha blocking drugs, e.g. Infliximab

Reactive arthritis

• Sterile synovitis following dysentery or a sexually acquired infection

Aetiology

• Trigger organism
• Salmonella
• Shigella
• Yersinia
• Chlamydia
• Ureasplasma

Clinical features

• Acute symmetrical lower limb arthritis
• Male more than female
• Often also an enthesitis e.g. plantar faciitis
• Non-articular features
• Acute anterior uveitis
• Circinate balanitis
• Keratoderma blenorrhagica
• Nail dystrophy
• Conjunctivitis
• Reiter's disease = urethritis, arthritis, and conjunctivitis

Management

• Treatment usually symptomatic with NSAIDs or steroid injections
• Treat underlying infection with antibiotics

Inflammatory bowel disease (IBD) - associated arthritis

• 10-15% of patients with IBD
• Lower limb joints
• In UC treatment of bowel disease may improve arthritis
• In Crohn's disease arthritis persists even when bowel is disease inactive
• 5% have sacroiliitis (independent of activity of IBD)
• Treatment with intra-articular steroids and sulfasalazine

Gout

• Inflammatory arthritis associated with hyperuricaemia and urate crystal deposition

Epidemiology

• 5% of the population have hyperuricaemia
• 0.2% of the population have gout
• Male > female
• Commonly presents between 30 and 50 years
• Rare in women before the menopause
• Familial or sporadic
• HLA-DR4 positive in 50-70%

Aetiology

• Causes of hyperuricaemia

Clinical features

• Acute onset
• Acute painful, red, swollen joint
• Often affects first MTP joint
• Precipitated by
• Alcohol
• Excess food
• Dehydration
• Diuretics

Investigations

• Joint fluid microscopy - needle shape crystals
• Serum urate
• Urea and electrolytes

Management

• NSAIDs
• Colchicine (particularly if NSAIDs cannot be used)
• If attacks are frequent give allopurinol to reduce urate 4-6 weeks after acute attack
• Lifestyle advice, e.g. diet, reduce alcohol intake

Chronic tophaceous gout

• Very high serum urate
• White urate deposits (tophi) in skin particularly ear lobes and around joints
• Associated with renal failure or use of diuretics

Septic arthritis

Aetiology

• Direct injury
• Blood-borne infection
• Susceptibility in
• Chronically inflamed joints
• Immunosuppressed patients
• Artificial joints

Organisms

• Staphylococcus aureus
• Streptococcus and other staphylococci
• Neisseria gonorrhoeae
• Haemophilus influenzae
• Gram-negative organisms

Clinical features

• Joint pain (may be severe)
• Muscle spasm
• Joint hot, red and swollen
• Signs of the source of infection

Investigations

• Urgent joint aspiration
• Microscopy and culture/gram stain
• Elevated white cell count
• Blood cultures

Management

• Two i.v. antibiotics for 2 weeks (start antibiotics immediately diagnosis suspected)
• Followed by 6 weeks of oral antibiotics
• Initial mobilisation of the joint
• Early physiotherapy
• Consider surgical drainage and washout

EMQ revision - Weakness in the legs

• 60 year old, Female, Bilateral proximal muscle weakness in the legs and dysphagia, Purple rash on cheeks
• Polymyositis
• Non-neurological causes of weakness in legs
• Polymyositis is an autoimmune disease characterised by non-suppurative inflammation of skeletal muscle
• Severe disease involves respiratory muscle weakness and cardiac involvement
• 40 year old, Male, Progressive weakness in arms and legs and episode of diarrhoea, Flaccid weakness of limbs and no reflexes
• Guillain-Barre Syndrome
• Describes a presentation of an ascending polyneuropathy of unknown aetiology, which may be associated with a preceding infection
• Weakness is symmetrical and affects proximal muscles sooner than distal ones
• Cranial nerves and the autonomic nervous system may also be involved
• Involvement of respiratory muscles can be fatal and regular monitoring of vital capcity is important
• In these cases it is often safer to initiate ventilation sooner rather than later
• Sensory symptoms are usually mild with complaints of numbness and tingling in the limbs
• Intravenous immunoglobulin is often used to shorten the duration of the disease
• Prognosis is good with over 85% of patients making a complete or near complete recovery
• 55 year old, Male, Bilateral progressive worsening muscle weakness, Marked wasting of lower limb muscles and very brisk lower limb reflexes, Sensation normal
• Motor Neuron Disease (MND)
• Progressive degenerative disease that affects the upper and lower motor neurons
• NO sensory involvement characteristically
• Pattern
• Progressive muscular atrophy
• Anterior horn wasting lesion with wasting often beginning in the distal muscles of the hand and then spreading. Fasciculation is a common finding
• Amyotrophic lateral sclerosis
• Involvement of the lateral corticospinal tract gives a progressive spastic teraparesis/paraparesis
• The presence of LMN signs, e.g. wasting, fasciculation differentiates this diagnosis from other causes of spastic weakness
• Progressive bulbar palsy
• The lower cranial nerve nuclei and their connections are primarily affected
• Dysarthria and dysphagia are common symptoms
• This pattern of disease is more common in women than in men
• 13 year old, Male, Bilateral pes cavus, Clawing of the toes, There is atrophy of peroneal muscles, Reduced reflexes and sensation distally
• Charcot-Marie-Tooth disease
• Progressive peroneal muscle atrophy
• Autosomal dominant or recessive
• Now described as a hereditary sensorimotor neuropathy (HSMN) because several clinical variants have been identified associated with different gene defects
• HSMN types I and II are the most common types
• HSMN type I is a demyelinating neuropathy of insidious onset presenting typically in the first decade of life with foot deformities (e.g. pes cavus), muscle weakness (distal weakness that affects legs earlier and more severely than arms) and loss of balance. The presence of foot drop results in frequent trips and falls
• HSMN type II usually presents later in the second decade of life. The weakness in distal lower limb muscles is often accompanied by distal sensory loss. Foot deformities are less marked than in type I disease and patients may even be completely asymptomatic
• 30 year old, Bilateral leg weakness, Blurred vision, Fundoscopy reveals pale optic discs bilaterally
• Multiple Sclerosis
• In this case the pale bilateral optic discs indicate previous subclinical episodes of optic neuritis
• Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that has a progressive course
• There is an increased prevalence further away from the equator but the aetiology is still unknown
• More women are affected
• Diagnosis is made clinically but magnetic resonance imaging (MRI) is the imaging of choice to detect demyelinating plaques
• CSF examination usually shows oligoclonal bands of IgG on electrophoresis
• Electrophysiological tests reveal delays in the propagation of potentials (e.g. visual, somatosensory, auditory evoked potentials)
• Intravenous methylprednisolone can reduce the severity of relapses but does not improve long-term prognosis
• Interferon-beta has been shown to reduce the relapse rate in patients suffering from relapsing-remitting form of the illness but its use is limited because of its high cost

Mood (affective) disorders

• Spectrum of disorders ranging from depression through to mania
• Patients who suffer attacks of both have bipolar disorder

Aetiology

• Physical
• Genetic - monozygotic twin concordance 30-60%
• Neurotransmitter imbalance - downregulation of 5HT receptors in depression
• Hormonal
• Cortisol (Cushing's syndrome induces depression and corticosteroids alter mood, moreover hypercortisolaemia occurs in patients with depression)
• Oral contraceptives/ pregnancy/ premenstrual
• CNS abnormalities - brain MRI/PET studies show:
• Increased ventricular volume, frontal lobe atrophy and altered blood flow
• Volume reduction in the hippocampus
• Psychological
• Maternal deprivation
• Learned helplessness
• Social
• Stressful life events e.g. divorce, unemployment
• Sexual abuse in childhood

Clinical features

Depression

• Mood
• Depressed
• Miserable
• Unhappy
• Talk
• Slow
• Impoverished
• Monotonous
• Energy
• Reduced
• Apathetic/lethargic
• Ideation
• Feelings of
• Futility
• Guilt
• Self-reproach
• Unworthiness
• Hypochondriasis
• Worrying
• Suicidal thoughts
• Delusions of guilt
• Nihilism
• Persecution
• Cognition
• Impaired learning
• Pseudodementia if elderly
• Physical
• Early waking
• Poor appetite
• Weight loss
• Constipation
• Loss of libido
• Erectile dysfunction
• Fatigue
• Body aches and pains
• Behaviour
• Poverty of movement/expression
• Retardation/agitation
• Hallucinations
• Auditory
• Hostile
• Critical

Mania

• Mood
• Elevated
• Labile
• Irritable
• Talk
• Fast
• Pressurised
• Flight of ideas
• Energy
• Excessive
• Ideation
• Grandiose
• Self-confident
• Delusions of
• Wealth
• Power
• Influence
• Religious significance
• Persecutory delusions
• Cognition
• Disturbance of registration of memories
• Physical
• Insomnia
• Weight loss
• Behaviour
• Disinhibition
• Increased sexual interest
• Hallucination
• Excessive drinking/spending
• Fleeting auditory
• Occasionally visual

Can range from severe life-threatening disease to minor forms

Differential diagnosis

• Mania
• Drug-induced psychosis
• Amphetamines/ecstasy/cocaine
• Long term cannabis use
• Steroids
• Acute schizophrenia
• Hyperthyroidism/Cushing's syndrome
• Depression
• Malignancy
• Hypothyroidism/hyperparathyroidism
• Cushing's syndrome
• Neurological diseases (multiple sclerosis, Parkinson's)
• Cerebral ischaemia or tumour
• Heart failure
• Porphyria
• Drugs
• Steroids
• Psychiatric disorders
• Schizophrenia
• Alcohol/drug (e.g. amphetamines) misuse or withdrawal
• Borderline personality disorder
• Dementia
• Normal bereavement reaction
• Onset
• Immediately after loss
• Duration
• Weeks
• Pattern
• Slow acceptance and adjustment
• Grief
• Expressed openly
• Guilt
• Mild regret in early stage
• Morbid grief reaction
• Onset
• Delayed for weeks/months
• Duration
• Months/years
• Pattern
• Denial of loss and refusal to accept implications
• Grief
• Expressed with difficulty
• Guilt
• Marked guilt often present

Management

• Physical
• Stop depressing drugs including alcohol
• Regular exercise (good for mild/moderate depression)
• Depression
• Drugs - choice depends on side-effects and safety
• Serotonin reuptake inhibitors, e.g. fluoxetine
• Tricyclic antidepressants (TCAs), e.g. amytriptyline
• New generation antidepressants e.g. venlafaxine - serotonin and noradrenaline receptor blocker, mirtazapine increases both noradrenaline and selective serotonin transmission noradrenaline reuptake inhibitors, e.g. reboxetine
• Monoamine oxidase inhibitors, e.g. phenelzine - used 2nd line
• Electroconvulsive therapy (ECT)
• Used in life-threatening depression
• Mania
• Acute attacks
• Lithium
• Neuroleptic drugs for severe hyperactivity e.g. haloperidol
• Prophylaxis
• Lithium
• Regular check on drug levels (narrow therapeutic window)
• Regular check on renal function (renal excretion)
• Regular check on thyroid function
• Carbamazepine
• Valproate
• Psychological
• Psychotherapy
• Cognitive/behavioural therapy
• Social
• Assistance with social problems
• Group support
• Stress management
• Family/carer support

EMQ revision - Headache

• 56 year old, Female, Unilateral stabbing pain on the surface of her scalp and around her eye, Pain is precipitated by washing or touching the specific area
• Trigeminal neuralgia
• Ophthalmic division of the trigeminal nerve
• Usually affects the Maxillary and Mandibular divisions
• 28 year old, Female, Headache and double vision which is worse when lying down, Examination reveals papilloedema but no feocal signs, There are no abnormal findings on CT
• Benign intracranial hypertension
• Usually affects obese women
• Steroids and tetracyclines are recognised precipitants
• Raised CSF pressure made in LP
• Symptoms often resolve after LP
• Chronic treatment includes the use of repeated LPs and diuretics
• 30 year old, Male, Dull headache worse when lying down or when coughing, Recently suffered a seizure
• Space-occupying lesion
• Raised intracranial pressure
• Development of seizures is sinister finding and urgent imaging is warranted
• 65 year old, Female, Complains of constant aching pain around the right eye radiating to the forehead, Reduced vision in the eye, Red and congested with a dilated pupil
• Acute glaucoma
• Long-sighted elderly population affected more
• Blockage of drainage of aqueous humour from the anterior chamber via canal of Schlemm
• Stimuli that cause pupillary dilatation (e.g. sitting in the dark) increases the tightness of contact between the iris and the lens and can precipitate an attack
• 70 year old, Female, Headache, Drowsiness, Unsteadiness over last couple of days, Examination reveals papilloedema, Falling 3 weeks ago
• Subdural haematoma
• Not always prior history of head injury
• Alcohol abuse is a risk factor for chronic subdural haemorrhage
• Neurosurgical opinion should be sought early, althugh many subdural haemorrhages can be handled conservatively because the bleeds clot spontaneously
• The presence of papilloedema indicates that the subdural bleed is increasing the intracranial pressure
• Initially the intracranial compliance is high and so the increase in volume caused by the developing bleed causes only small increases in intracranial pressure
• However, this compliance decreases (compensatory mechanisms to cope with increases in pressure are limiting)
• And small increases in volume are associated with large increases in intracranial pressure
• This is clinically important because patients may deteriorate very rapidly and therefore should be regularly monitored
• 40 year old, Male, Severe headache of sudden onset 4h ago, As if kicked in the back of the head, Vomited twice and is now feeling stiff in the neck
• Subarachnoid haemorrhage
• Rupture of berry aneurysms found on the circle of Willis
• Disease states associated with high blood pressure (e.g. coarctation of the aorta, polycystic kidney disease or defective collagen synthesis, e.g. Ehlers-Danlos syndrome, predispose to berry aneurysm formation)
• Typical symptoms are of a severe occipital headache that is sometimes likened to being 'kicked in the back of the head'
• Initial investigation of choice is a CT brain scan
• However, findings can be negative in 10-15 percent of subarachnoid haemorrhage
• In patients in whom clinical suspicion is high and CT scan is negative, lumbar puncture (LP) should be performed
• Subarachnoid haemorrhage is confirmed by presence of xanthochromia resulting from denatured red blood cells within the cerebrospinal fluid (CSF)
• This can take up to 12h to form and therefore, LP should be delayed for at least 12h after onset of headache. Discolouration of the CSF should be uniform, unlike a bloody tap where more red blood cells are present in the initial samples
• Some patients may present with a small sentinel bleed with minimal symptoms
• It is important to make this diagnosis because timely intervention may prevent a more catastrophic later event
• 40 year old, Businesswoman, Headache that feels like a tight band around her head
• Tension headache
• Diagnosis requires absence of symptoms and signs of other types of headache
• Treatment is rarely effective and avoidance of precipitants, e.g. stress, is the best remedy
• Chronic use of analgesics can lead to 'rebound headache' on withdrawal
• Antidepressants are prescribed with uncertain benefit
• 55 year old, Woman, Headache that had lasted a few weeks, Pain in her jaw during meals and scalp is tender to palpation
• Giant cell arteritis
• Medium-sized vessel vasculitis
• Classifically it affects the temporal vessels giving symptoms of headache, scalp tenderness and jaw claudication
• There is a risk of blindness if the disease is left untreated and treatment should be commenced empirically on oral corticosteroids
• Diagnosis can be confirmed with a temporal artery biopsy and the condition is usually associated with a high erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP)
• CRP is always elevated, although ESR is occasionally normal
• As disease may not affect the part of the artery that has been biopsied, treatment should be continued even though the biopsy is negative if the clinical suspicion is high. Giant cell arteritis is recognised to overlap with polymyalgia rheumatica
• 30 year old, Man, Rapid-onset pain around his left eye every night for the last 2 weeks, Associated with lid swelling, Watery eye and flushing. Suffers from these bouts every 3 months
• Cluter headache
• Recurrent brief attacks of headache around the eye
• The hallmark of cluster headache is the association with autonomic symptoms and signs, e.g. nasal stuffiness, conjunctival hyperaemia, Horner's syndrome
• The clusters usually last between a few weeks and a few months
• 24 year old, Woman, Unilateral throbbing headache lasting 6 hours associated with vomiting and photophobia, Several episodes in the past
• Migraine
• The classic description of migraine includes a preceding aura before the onset of the headache, but this feature does not occur in most patients

Cluster headaches

Cluster headaches

• Affects adults in third and fourth decades
• Males more than females

Clinical features

• Recurrent bouts of excruciating pain centred around one eye
• Wakes patient up at night
• Vomiting
• Watering and congestion of affected eye
• Transient ipsilateral Horner's syndrome

Management

• Usually unhelpful
• No analgesia effective for headache
• Lithium carbonate for prophylaxis
• Oxygen during attack

Neurological OSCE overview part 2

Cranial nerves

General observation

• Ptosis (3)
• Facial droop or asymmetry (7)
• Hoarse voice (10)
• Articulation of words, dysarthria (5,7,10,12)
• Abnormal eye position (3,4,6)
• Abnormal or asymmetrical pupils (2,3, sympathetic and parasympathetic)

Cranial nerve 1 - Olfactory nerve

• Ask the patient about changes in or absence of sense of smell

Cranial nerve 2 - Optic nerve

• Examination with ophthalmoscope
• Papilloedema
• Optic atrophy
• Maculopathy
• Hypertensive or diabetic retinopathy

• Visual acuity with Snellen's chart
• Allow the patient to use glasses
• Ask the patient to read a Snellen eye chart with each eye
• Record the smallest line the patient can read for each eye
• Visual acuity is reported as a pair fo numbers (20/20) where the first number represents how far the patient is from the chart and the second number is the distance from which the 'normal

• Visual fields
• Position yourself at eye level a metre or so in front of the patient and ask him/her to look into your eyes
• Hold your hands out to the sides halfway between you and the patient and wriggle a finger on both hands asking the patient to indicate which side he/she sees the finger move; if the patient only sees one side this indicates a lateral field defect or sensory neglect on that side
• Test the four quadrants of each eye while asking the patient to cover the opposite eye comparing with your own fields of vision for the appropriate eye

• Test pupillary reactions
• Ask the patient to look into the distance
• Shine a bright light obliquely into each pupil in turn
• Look for both the direct (same eye) and consensual (other eye) reactions
• Test accommodation
• Hold your finger about 10cm from the patient's nose
• Ask him/her to look into the distance and then at your finger
• Look for constriction of the pupil and convergence of the eyes to near vision

Cranial nerve 3 - Oculomotor nerve

• Look for ptosis
• Test extraocular movements (superior, medial and inferior rector and inferior oblique muscles)
• Holding your finger about 1 metre in front of the patient, ask him/her to follow your finger with the eyes without moving the head
• Check horizontal, vertical, and oblique gaze using a cross or 'H' pattern, ask about diplopia
• Pause during upward and lateral gaze to check for nystagmus
• Test pupillary reactions to light

Cranial nerve 4 - Trochlear nerve (Superior oblique muscle)

• Inward and downward movement of eyes

Cranial nerve 6 - Abducens nerve (Lateral rectus muscle)

• Lateral eye movement

Cranial nerve 5 - Trigeminal nerve

• Motor
• Ask the patient to first open the mouth and then clench the teeth
• Palpate the temporal and masseter muscles as this is done
• Sensory
• On both sides, use cotton wool to test
• The forehead (olfactory division)
• The cheeks (maxillary division)
• The jaw (mandibular division)
• Corneal reflex
• Ask the patient to look up and away
• From the other side, touch the cornea (not sclera) lightly with a fine wisp of cotton wool
• Look for the normal blink reaction of both eyes
• Repeat on the other side

Cranial nerve 7 - Facial nerve

• Observe for any facial droop or asymmetry
• Ask the patient to do the following, noting any weakness of asymmetry
• Raise eyebrows
• Close both eyes tightly
• Smile or show the teeth
• Puff out the cheeks
• Central vs peripheral
• With an upper motor neurone lesion (stroke), crossover of innervation means function is preserved over the upper part of the face (forehead, eyebrows, eyelids)
• With a lower motor neurone lesion (Bell's palsy), the entire side of the face droops

Cranial nerve 8 - Vestibulocochlear nerve

• Rub your fingers together next to one ear while whispering a number in the other and ask the patient to tell you the number
• Repeat for the other side
• Weber's test
• Use a 512 Hz tuning fork
• Place the base of the vibrating tuning fork firmly on top of the patient's head
• Ask the patient where the sound appears to be coming from (normally in the midline)
• In sensorineural deafness there will be deafness in the affected ear
• In conductive deafness, the sound will be heard better in the deaf ear
• Rinne's test (to compare air and bone conduction)
• Use a 512 Hz tuning fork
• Place the base of the vibrating tuning fork against the mastoid bone behind the ear
• Whent he patient no longer hears the sound, hold the end of the fork near the patient's ear and ask if he or she can hear it now (air conduction is normally greater than bone conduction)
• In conductive deafness bone conduction is better than air conduction

Cranial nerve 9/10 - Glossopharyngeal and vagus

• Ask the patient to swallow a sip of water, look for choking or dribbling
• Ask the patient to say 'Agh', watching the movements of the soft palate and the pharynx. The uvula deviates away from the affected side
• Test the gag reflex (unconscious patient)
• Touch the back of the throat on the soft palate with an orange stick on each side
• It is normal to gag after each stimulus
• Ka La Mi
• Ka = 10
• La = 12
• Mi = 7

Cranial nerve 11 - Accessory

• From behind, look for wasting of the trapezius muscles
• Ask the patient to shrug the shoulders against resistance
• Ask the patient to turn the head against resistance
• Watch and palpate the sternocleidomastoid muscle on the opposite side

Cranial nerve 12 - Hypoglossal

• Look at the tongue for wasting or fasciculation (lower motor neurone lesion)
• Ask the patient to
• Protrude the tongue
• Move the tongue from side to side
• The tongue moves towards the side of any lesion

Other causes of headache

• Subarachnoid haemorrhage
• Meningitis
• Sinusitis
• Brain tumours
• Temporal arteritis
• Benign intracranial hypertension
• Head injury

Classical migraine

Classical migraine

Clinical features

Prodrome

• Teichopsia (flashes)
• Jagged lines
• Unilateral patchy scotoma
• Lasts 15 minutes to 1 hour

Headache hemicranial or generalised

• Nausea and vomiting
• Generally irritable
• Preference for the dark
• Sleeping

Other patterns

• Migraine without aura
• Hemiplegic migraine

Differential diagnosis

• Subarachnoid haemorrhage
• Transient ischaemic attack
• Partial seizures

Management

• Avoid precipitating factors

During attack

• Paracetamol
• Antiemetics
• Sumatriptan (5HT agonist)
• Ergotamine

Prophylaxis

• Pizotifen, methysergide (5HT antagonists)
• Propranolol
• Amitriptyline (low-dose)

Tension headache

Tension headache

• The vast majority of chronic or recurrent headaches

Clinical features

• Throbbing headache
• Tight band sensation
• Pressure behind eyes

Management

• Avoid precipitating causes
• Simple analgesia

Migraine

• Recurrent headaches associated with visual and gastrointestinal disturbance

Pathology

• Vasodilatation and oedema of blood vessels
• Release of vasoactive substances

Parkinson's disease

Parkinson's disease

• Combination of tremor, rigidity, akinesia and postural hypotension

Prevalence

• Increases with age
• 1:200 over 70 years of age
• Less prevalent in smokers

Aetiology

• Idiopathic
• Drug induced, e.g. phenothiazines
• MPTP (methylphenyltetrapyridine, impurity in illegally synthesised opiates)
• Encephalitis lethargica

Pathology

• Cell degeneration in substantia nigra
• Loss of dopamine in the extrapyramidal nuclei

Clinical

• Tremor - 4-7 Hz resting tremor (pill-rolling)
• Micrographia
• Rigidity - increased tone throughout the range of movement
• Cogwheel rigidity (stuttering rigid tone combined with tremor)
• Bradykinesia - poverty of movement
• Falls
• Mask-like facies
• Reduced blinking
• Stooping, shuffling gait (festinant)
• Poor arm swinging
• Monotonous speech, slurring dysarthria
• Normal power
• Brisk reflexes
• Downgoing plantars
• Cognitive function initially preserved; late dementia sometimes occurs

Investigations

• No diagnostic test; diagnosis made on clinical grounds

Management

• Levodopa plus dopa decarboxylase inhibitor (e.g. Sinemet or Madopar; start gradually increasing the dose until adequate response or limiting side-effects)
• Dopaminergic agonists, e.g. bromocriptine
• Selegiline - monoamine oxidase B inhibitor
• Neurosurgery (occasionally for intractable tremor)
• Physiotherapy
• Physical aids

Side-effects of levodopa

• Short-term
• Nausea and vomiting
• Confusion
• Visual hallucinations
• Chorea 
• Long-term
• End-of-dose dyskinesia
• On-off syndrome
• Chorea
• Dystonic movements

Prognosis

• Variable
• Usually worsens over 10-15 years with death from bronchopneumonia