Diseases Flashcards
How is malaria spread?
Through the bite of the female anopheles mosquito
Name the five species of protozoa which cause malaria.
- Plasmodium falciparum
- Plasmodium ovale
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium knowlesi
How is malaria diagnosed?
- Thick blood film to identify disease
- Thin blood film to identify species
- Rapid diagnostic tests to detect antigen
What are the symptoms of malaria?
- Fever (usually fluctuating)
- Chills
- Headache
- Myalgia
- Fatigue
- Diarrhoea
- Vomiting
- Abdominal pain
What are the signs of malaria?
- Anaemia
- Jaundice
- Hepaosplenomegaly
- ‘Black water fever’ - dark urine
Briefly describe the pathophysiology of malaria.
- Sporozoites infect hepatocytes in liver
- Develops into schizont
- Schizont bursts and infects red blood cells
- Schizont forms in red blood cell and bursts
Which plasmodium species can form hypnozoites in the liver which can reactivate malaria?
- Ovale
- Vivax
Which plasmodium species causes complicated malaria?
Plasmodium falciparum
Briefly describe the pathophysiology of complicated malaria.
Red blood cells have proteinaceous knobs which bind to endothelial cells and obstruct small vessels.
What are the complications of complicated malaria?
- Vascular occlusion and hypoglycaemia in brain
- Acute respiratory distress syndrome
- Renal failure
- Thrombocytopenia and DIC
- Shock
What is the treatment for uncomplicated malaria?
Chloroquine
What is the treatment for complicated malaria?
- Artesunate
OR - Quinine and doxycycline
What are some supportive measures that can be given in complicated malaria?
- Antiepileptics
- Oxygen
- Diuretics
- Ventilation
- Fluids
- Dialysis
- Broad spectrum antibiotics
- Blood products
What should be given to prevent a malaria relapse?
What precaution should be taken before treatment?
Primiquine
Screen for G6PD deficiency)
Name the virus which causes HIV.
HIV1
Give five risk factors for having HIV.
- Africa
- Homosexuality less accepted
- Men who have sex with men
- IV drug abusers
- HIV positive mother
Briefly describe the pathophysiology of HIV.
- HIV gp120 binds to CD4 receptors
- Cells migrate to lymphoid tissue and virus replicates
- Virions released from host cell by budding
Describe the seroconversion stage of HIV.
Initial stage of the primary infection.
May be accompanied by transient illness after exposure.
Describe the asymptomatic infection in HIV.
Battle between the virus and the immune system.
Some people have generalised lymphadenopathy.
What is AIDS-related complex?
A stage in the HIV infection where constitutional symptoms develop.
What is AIDS?
HIV + an indicator disease
What is the typical time scale from HIV to AIDS?
8 years
What symptoms may be experienced in HIV seroconversion?
- Fever
- Myalgia
- Pharyngitis
- Rash
What are the signs of generalised lymphadenopathy?
Nodes >1cm in diameter at >2 extra-inguinal sites.
What are the constitutional symptoms experienced in AIDS-related complex?
- High temperature
- Night sweats
- Diarrhoea
- Weight loss
- Minor opportunistic infections
What symptoms indicate HIV progression?
- Chronic fever
- Cough >1month
- Chronic diarrhoea
- Oral thrush
- Weight loss
- TB
- Herpes zoster
How is HIV diagnosed?
Serum HIV antibody
When might the HIV antibody test be negative even when the person is infected?
1-3 weeks after exposure
How can HIV diagnosis be confirmed if antibody test is negative 1-3 weeks after exposure?
- HIV RNA
- HIV core antigen
- Repeat antibody test at 6 weeks and 3 months
Give three techniques to prevent HIV.
- Blood screening
- Disposable equipment
- Antenatal antiretrovirals if HIV +ve mother
What is HAART?
Highly active antiretroviral therapy
How many drugs, and what types should be used in HAART?
At least 3 drugs.
NRTI, NRTI, and one other.
What are nucleoside reverse transcriptase inhibitors?
Substitute nucleotide bases used to treat HIV.
What types of drugs can be used in antiretroviral treatment?
- Nucleoside reverse transcriptase inhibitors
- Protease inhibitors
- Non-nucleoside reverse transcriptase inhibitors
- CCR5 antagonists
- Integrase inhibitors
Why are three different drugs used in HAART?
Monotherapy causes drug resistance by selecting for resistant strain and allowing it to replicate.
Give four cancers that patients with HIV are at an increased risk of.
Why is the risk increased?
- Kaposi’s sarcoma
- Lymphomas
- Cervical cancer
- Hepatocellular carcinoma
THESE CANCERS ARE ALL CAUSED BY VIRUSES
What is the most common opportunistic infection in HIV?
Pneumocystis pneumonia
What are the criteria for a diagnosis of AIDS?
CD4 count <200 and AIDS defining illness
What is the normal CD4 range?
500-1500
Briefly describe the pathophysiology of a paracetamol overdose.
More toxic NAPQI is produced and there’s not enough glutathione to get rid of it so it builds up.
How can alcohol cause a paracetamol overdose?
Alcohol induces the CYP450 which forms NAPQI
What are the signs/symptoms of a paracetamol overdose?
- None initially
- May have vomiting or right upper quadrant pain
- Later symptoms include jaundice, encephalopathy, acute kidney injury
What is the treatment for a paracetamol overdose in the last four hours?
Activated charcoal
What is the treatment for a paracetamol overdose if ingestion occurred more than four hours ago?
IV N-acetylcysteine
Give a definition of sepsis.
Inflammatory response causing damage to tissues of the body.
Give the general criteria for diagnosis of sepsis.
Systemic inflammatory response syndrome + presence of an infection
Briefly describe the pathophysiology of sepsis.
Cytokine cascades, free radical production, and release of vasoactive mediators cause vasodilation and circulatory failure, leading to inadequate organ perfusion.
What are the signs/symptoms of sepsis?
- Warm
- Vasodilation
- Bounding pulse points
- Tachycardia
- Hypotension
- Narrow pulse pressure
- Evidence of tissue hypoperfusion (mottled skin, low urine output, high lactate)
- Low GCS/agitation
- Pallor
- Cool peripheries
- Slow capillary refill
- Tachypnoea
What is the management of sepsis?
- Take cultures
- Start antibiotics (broad spectrum)
- IV fluids
- Low dose steroids may improve BP but not mortality
Give seven red flags for sepsis.
- lactate >2
- Purpuric rash
- Heart rate >130
- Requires O2 to maintain sats
- Resp rate >25
- V or less on AVPU
- Systolic BP <90
In systemic inflammatory response syndrome, 2 out of the following 4 features are present…
- Temperature >38 or <36
- Tachycardia >90bpm
- Respiratory rate >20bpm or PaCO2 <4.3KPa
- WBC >12x10^9 /L or >10% immature forms
Define severe sepsis.
Sepsis with evidence of organ hypoperfusion
Define septic shock.
Severe sepsis with hypotension
What is acromegaly?
Increased secretion of growth hormone from pituitary adenoma.
What is the alternative name for acromegaly if it occurs before puberty?
Gigantism
Briefly describe the pathogenesis of acromegaly.
Increased rate of bone and soft tissue growth by stimulating secretion of IGF-1.
How is gigantism caused by a pituitary adenoma before puberty?
- Increased secretion of growth hormone
- Tumour presses on normal pituitary so puberty is suppressed and epiphyses don’t fuse
Describe the rate of symptom onset in acromegaly.
Slow
Does acromegaly affect more men or women?
Affects men and women equally
What are the symptoms of acromegaly?
- Acroparaesthesia (burning/tingling in peripheries)
- Amenorrhoea
- Decreased libido
- Headache
- Increased sweating
- Snoring
- Arthralgia (joint pain)
- Backache
What are the signs of acromegaly?
- Increased growth of hands, jaw, and feet
- Coarsening face, wide nose
- Big supraorbital ridges
- Macroglossia (big tongue)
- Widely spaced teeth
- Puffy lips and eyelids
- Greasy and thick skin
- Scalp folds
- Skin darkening
- Acanthosis nigricans (dark discolouration in skin folds and creases)
- Laryngeal dyspnoea
- Obstructive sleep apnoea
- Goitre
- Proximal weakness and arthropathy
- Carpel tunnel
- Signs from pituitary mass
- Prognathism
- Frontal bossing
What are the complications of acromegaly?
- Insulin resistance
- Hypertension
- Left ventricular hypertrophy, cardiomyopathy, arrhythmias
- Increased risk of ischaemic heart disease and stroke
- Increased colon cancer risk
- Cerebral vascular events and headache
- Arthritis
- Sleep apnoea
How can acromegaly be diagnosed?
- Clinical features
- GH
- IGF-1
- Glucose tolerance test (glucose suppresses GH)
What random serum measurements can exclude acromegaly?
- GH <0.4ng/ml
- Normal IGF-1
What glucose tolerance test measurements can exclude acromegaly?
- Normal IGF-1
- GH <1ng/ml
What is the treatment for acromegaly?
- Pituitary surgery (mainstay of treatment)
- Medical therapy
- Radiotherapy
What medical therapy can be used to treat acromegaly?
- Dopamine agonists
- Somatostatin analogues
- Growth hormone receptor antagonists
Is prolactinoma more common in men or women?
Women
Briefly describe the pathophysiology of prolactinoma.
Lactotroph cell tumour of the pituitary
Give two other things, other than prolactinoma, that can cause hyperprolactinaemia.
- Compression of pituitary stalk
- Dopamine antagonists
What are the clinical features of prolactinoma?
- Tumour mass effects
- Menstrual irregularity/amenorrhoea
- Infertility
- Galactorrhoea
- Low libido
- Low testosterone (men)
What are the complications of prolactinoma?
- Hypogonadism
- Osteoporosis
When will measuring serum prolactin levels cause a false result?
In patients on antidopaminergic drugs
How is prolactinoma treated?
Using dopamine agonists
Briefly describe the pathogenesis of Cushing’s syndrome.
Excess cortisol
What is Cushing’s disease?
Pituitary adenoma secreting ACTH
What are five sources of excess cortisol in Cushing’s disease?
- Exogenous steroids
- Pituitary adenoma (Cushing’s disease)
- Ectopic tumour
- Synthetic ACTH
- Adrenal tumour
What are the symptoms of Cushing’s syndrome?
- Increased weight
- Mood change
- Proximal weakness
- Gonadal dysfunction
- Acne
- Recurrent Achilles tendon rupture
What are the signs of Cushing’s syndrome?
- Central obesity
- Plethoric (red face)
- Moon face
- Buffalo hump
- Supraclavicular fat distribution
- Skin and muscle atrophy
- Bruises
- Abdominal striae
- Osteoporosis
- Increased blood pressure
- Increased blood glucose
- Infection-prone
- Poor healing
- Short stature
Why can’t Cushing’s syndrome be diagnosed using random cortisol?
Cortisol is affected by illness, time of day, and stress.
How is Cushing’s disease diagnosed?
Overnight dexamethosome suppression test.
Usually suppresses cortisol overnight but doesn’t in Cushing’s syndrome
What is the treatment for iatrogenic Cushing’s syndrome?
Ideally stop medications
What is the treatment for Cushing’s syndrome caused by any type of tumour?
Surgery
What is primary adrenal insufficiency also known as?
Addison’s disease
What causes secondary adrenal insufficiency?
- Hypopituitarism
- Steroids (suppression of HPA)
Briefly describe the pathogenesis of primary adrenal insufficiency.
Destruction of the adrenal cortex due to adrenal antibodies, very long chain fatty acids, imaging, or genetic factors.
What are the symptoms of adrenal insufficiency?
- Fatigue
- Weight loss
- Poor recovery from illness
- Adrenal crisis
- Headache
- Dizziness
- Fainting
- Nausea/vomiting
- Abdominal pain
- Diarrhoea/constipation
What are the signs of adrenal insufficiency?
- Pigmentation and pallor
- Hypotension
What are some factors associated with adrenal insufficiency?
- Past history of TB/postpartum bleed/cancer
- Family history of autoimmunity/congenital disease
- Past treatment with any steroids
What is the biochemistry associated with adrenal insufficiency?
- Low Na, High K
- Eosinophilia
- Borderline elevated TSH
How can adrenal insufficiency be diagnosed?
- 0900 cortisol and ACTH
- Synacthen test (ACTH stimulation test)
How can primary and secondary adrenal insufficiency be differentiated using blood tests?
Elevated renin/low aldosterone in primary
What is the treatment for adrenal insufficiency?
Hydrocortisone twice or three times daily.
Also replace aldosterone with fludrocortisone in primary.
Describe the presentation of adrenal crisis.
- Hypotension and cardiovascular collapse
- Fatigue
- Fever
- Hypoglycaemia
- Hyponatraemia and hyperkalaemia
Describe the management of adrenal crisis.
- Cortisol/ACTH bloods if possible
- Immediate hydrocortisone
- Fluid resuscitation
- Hydrocortisone 6 hourly
- In primary start fludrocortisone
What are the ‘sick day rules’ for a patient with adrenal insufficiency?
- Always carry 10x10mg hydrocortisone tablets
- Fever/flu = double dose of steroids
- If in doubt double dose of steroids
- Vomiting/increasingly unwell = emergency hydrocortisone injection
- In unable to inject take oral hydrocortisone and repeat if vomit
- Go to A and E or ring ambulance
What is thyrotoxicosis?
The clinical effect of excess thyroid hormone.
What are the symptoms of hyperthyroidism?
- Diarrhoea
- Weight loss
- Increased appetite
- Over-active
- Sweats
- Heat intolerance
- Palpitations
- Tremor
- Irritability
- Labile emotions
- Oligomenorrhoea/infertility
What are the signs of hyperthyroidism?
- Irregular/fast pulse
- Warm moist skin
- Fine tremor
- Palmar erythema
- Thin hair
- Lid lag
- Lid retraction
- Goitre, thyroid nodules, bruit
What are the signs of Graves’ disease?
- Eye disease (exophthalmos, ophthalmoplegia)
- Pretibial myxoedema
- Thyroid acropachy
How can hyperthyroidism be diagnosed?
- TSH low
- T3/T4 increased
- Check thyroid autoantibodies
- Isotope scan if cause is unclear
What are the causes of hyperthyroidism?
- Graves’ disease
- Toxic multinodular goitre
- Toxic adenoma
- Ectopic thyroid tissue
- Exogenous
Briefly describe the pathogenesis of Graves’ disease.
Circulating IgG autoantibodies binding to and activating thyrotropin receptors (TSH-R), causing thyroid enlargement.
Briefly describe the pathophysiology of thyroid eye disease.
TSH-R autoantibodies cross react with orbital autoantigens, causing retro-orbital inflammation and lymphocyte infiltration. This causes swelling of the orbit.
What is the treatment for hyperthyroidism?
- Drugs (b blockers to control symptoms)
- Anti-thyroid medication (titration/block and replace)
- Radioiodine
- Thyroidectomy
What are the complications of hyperthyroidism?
- Heart failure
- Angina
- Thyroid storm
- Atrial fibrillation
- Osteoporosis
- Ophthalmopathy
- Gynaecomastia
What is the main known risk factor for thyroid eye disease?
Smoking
What are the symptoms of thyroid eye disease?
- Eye discomfort
- Grittiness
- Increased tear production
- Photophobia
- Diplopia (double vision)
- Decreased acuity
- Afferent pupillary defect
What are the signs of thyroid eye disease?
- Exophthalmos (appearance of protruding eye)
- Proptosis (eyes protrude beyond orbit)
- Conjunctival oedema
- Corneal ulceration
- Papilloedema
- Loss of colour vision
- Ophthalmoplegia (eye paralysis)
What are the symptoms of hypothyroidism?
- Tired
- Sleepy
- Lethargic
- Low mood
- Cold-disliking
- Weight gain
- Constipation
- Menorrhagia
- Hoarse voice
- Decreased memory/cognition
- Dementia
- Myalgia
- Cramps
- Weakness
What are the signs of hypothyroidism?
- Bradycardic
- Reflexes relax slowly
- Ataxia (cerebellar)
- Dry thin hair/skin
- Yawning/drowsy/coma
- Cold hands
- Ascites
- Round puffy face/double chin/obese
- Defeated demeanour
- Immobile
- Congestive cardiac failure
- Neuropathy
- Myopathy
- Goitre
(Can remember most of them using the pneumonic BRADYCARDIC)
How can hypothyroidism be diagnosed?
- Increased TSH
- Decreased T4
- Thyroglobulin and thyroid peroxidase (TPO) antibodies (not specific for disease)
What are the causes of primary autoimmune hypothyroidism?
- Primary atrophic hypothyroidism
- Hashimoto’s thyroiditis
What are the causes of primary hypothyroidism?
- Iodine deficiency
- Thyroidectomy
- Radioiodine treatment
- Drug-induced
- Subacute thyroiditis
What drugs can cause hypothyroidism?
- Anti-thyroid drugs
- Amiodarone
- Lithium
- Iodine
What other conditions is hypothyroidism associated with?
- Other autoimmune conditions (T1DM, Addison’s, Pernicious anaemia)
- Turner’s/Down’s syndrome
- Cystic fibrosis
- Primary biliary cirrhosis
- Ovarian hyperstimulation
- Genetic conditions
What is the treatment for hypothyroidism?
Levothyroxine
Name the five types of thyroid cancer, in order of decreasing incidence.
- Papillary thyroid cancer
- Follicular thyroid cancer
- Medullary thyroid cancer
- Thyroid lymphoma
- Anaplastic thyroid cancer
Where does papillary thyroid cancer spread to and what is the treatment?
- Spreads to lymph nodes and lungs
- Treatment is total thyroidectomy with/without radioiodine
Where does follicular thyroid cancer spread to and what is the treatment?
- Spreads early via blood to bone/lungs
- Treatment is total thyroidectomy + T4 suppression + radioiodine abalation
What age range does papillary thyroid cancer commonly occur in?
Younger patients
What age range does follicular thyroid cancer usually occur in?
Middle age
Which type of thyroid cancer can be part of MEN syndrome?
Medullary thyroid cancer
What hormone can medullary thyroid cancers produce?
Calcitonin
What is the treatment for medullary thyroid cancer?
Thyroidectomy and node clearance
What should be screened for before a thyroidectomy in medullary thyroid cancer?
Phaeochromocytoma
Is thyroid lymphoma more common in males or females?
Females
How might a patient with thyroid lymphoma present?
- Stridor (high-pitched wheeze)
- Dysphagia (swallowing problems)
What is the treatment for thyroid lymphoma?
Chemoradiotherapy
What is the treatment for anaplastic thyroid cancer?
Poor response to any treatment, but excision and radiotherapy may be tried (in absence of unresectable disease)
What is a possible complication of Carbimazole?
Agranulocytosis
Why should corrected calcium level always be measured?
Low serum albumin may cause low total serum calcium.
What are the signs/symptoms of hypocalcaemia?
- Parasthesia (pins and needles)
- Muscle spasm
- Seizures
- Basal ganglia calcification
- Cataracts
- Long QT interval
- Chvostek’s sign
- Trousseau’s sign
What is Chvostek’s sign?
Tap the facial nerve and look for facial muscle spasm.
What is Trousseau’s sign?
Inflate BP cuff and look for hand spasm.
Give three causes of hypocalcaemia.
- Vitamin D deficiency
- Hypoparathyroidism
- Pseudohypoparathyroidism
Give two reasons why a blood test may show a false positive for hypercalcaemia.
Intracellular calcium release due to:
- tourniquet on for too long
- Old/haemolysed sample
What are the signs/symptoms of hypercalcaemia?
- Thirst
- Polyuria
- Nausea
- Constipation
- Confusion/coma
- Renal stones
- Short QT interval
Give the two major causes of hypercalcaemia.
- Malignancy
- Primary hyperparathyroidism
Give five other causes of hypercalcaemia.
- Thiazide diuretics
- Thyrotoxicosis
- Sarcoidosis
- Adrenal insufficiency
- Immobilisation
Give three malignancies that can cause hypercalcaemia.
- Bone metastases
- Myeloma
- Lymphoma
Briefly describe the pathophysiology of primary hyperparathyroidism.
80% due to single benign adenoma and 15-20% due to four gland hyperplasia (may be part of MEN I or MEN II).
Briefly describe the pathophysiology of secondary hyperparathyroidism.
Excessive secretion of parathyroid hormone due to hypocalcaemia.
Briefly describe the pathophysiology of tertiary hyperparathyroidism.
- Renal failure can’t activate vitamin D
- Decreased calcium absorption
- Increased PTH causes nodular hyperplasia and autonomy
What is the overall effect on serum calcium resulting from tertiary hyperparathyroidism?
Hypercalcaemia
What are the four consequences of hyperparathyroidism?
- Bones (osteitis fibrosa cystica, osteoporosis)
- Kidney stones
- Psychic groans (confusion)
- Abdominal moans (constipation and acute pancreatitis)
What are some causes of hypoparathyroidism?
- Various syndromes
- Developmental abnormality of third and fourth branchial pouches
- Genetic
- Surgical
- Radiation
- Autoimmune
- Infiltration
- Magnesium deficiency
Briefly describe the pathophysiology of pseudohypoparathyroidism.
Resistance to parathyroid hormone.
Describe what causes pseudohypoparathyroidism.
Type 1(a) Albright hereditary osteodystrophy, which is a mutation with a deficient Ga subunit.
What are the signs/symptoms of pseudohypoparathyroidism?
- Short stature
- Obesity
- Round facies
- Mild learning difficulties
- Subcutaneous ossification
- Short fourth metacarpals
- Other hormone resistance
What is pseudopseudohypoparathyroidism?
Same clinical phenotype as pseuohypoparathyroidism but with normal calcium metabolism (may have a partial mutation).
Describe the PTH, calcium, and phosphate levels in vitamin D deficiency.
High PTH
Low Calcium
Low phosphate
Describe the PTH, calcium, and phosphate levels in hypoparathyroidism.
Low PTH
Low calcium
High phosphate
Describe the PTH, calcium, and phosphate levels in pseudohypoparathyroidism.
High PTH
Low calcium
High phosphate
Describe the PTH, calcium, and phosphate levels in pseudopseudohypoparathyroidism.
Normal PTH
Normal calcium
Normal phosphate
Describe the PTH, calcium, and phosphate levels in hypercalcaemia of malignancy.
Low PTH
High calcium
Unpredictable phosphate
Describe the PTH, calcium, and phosphate levels in primary hyperparathyroidism.
High PTH
High calcium
Low phosphate
Describe the PTH, calcium, and phosphate levels in tertiary hyperparathyroidism.
High PTH
High calcium
High phosphate
What are the symptoms of diabetes insipidus?
- Polyuria
- Polydipsia
- No glycosuria
- Dehydration
- Symptoms of hypernatraemia
Describe the biochemistry and tests associated with diagnosis of diabetes insipidus.
- Urine volume >3L/day
- Inappropriately dilute urine for plasma concentration
- Serum osmolality >300 and urine osmolality <200
- Normonatraemia or hypernatraemia
- Water deprivation test
- Check renal function and serum calcium (hypercalcaemia causes same symptoms)
Briefly describe the pathophysiology of cranial diabetes insipidus.
Lack of vasopressin
What are some causes of cranial diabetes insipidus.
- Idiopathic
- Congenital
- Tumour
- Trauma
- Infections
- Vascular
- Inflammatory
How is cranial diabetes insipidus treated?
- Treat any underlying condition
- Desmopressin
Briefly describe the pathogenesis of nephrogenic diabetes insipidus.
Resistance to vasopressin action.
What are some causes of nephrogenic diabetes insipidus?
- Osmotic diuresis
- Drugs
- Chronic renal failure
- Post-obstructive uropathy
- Metabolic (low potassium, high calcium)
- Infiltrative
- Familial (X-linked, autosomal recessive)
What is the management of nephrogenic diabetes insipidus?
- Try and avoid precipitating drugs
- Free access to water
- Very high dose desmopressin
- Hydrochlorothiazide/indomethacin
What is primary polydipsia?
Causes same symptoms as diabetes insipidus but is just excessive thirst with no clear cause.
Briefly describe the pathophysiology of syndrome of inappropriate secretion of ADH.
Too much ADH when it should not be being secreted.
How does SIADH appear clinically?
Normal circulating volume and no oedema.
What are the signs/symptoms of SIADH?
- Low plasma sodium
- Low osmolality
- Inappropriately concentrated urine
- Water retention
Give five general causes of SIADH.
- CNS disorders
- Tumours
- Respiratory causes
- Endocrine causes
- Drugs
What is the management of SIADH?
- Diagnose and treat underlying condition
- Fluid restriction
- Sometimes demeclocycline
- If low sodium and fitting hypertonic saline in ITU
What are the symptoms of hyperglycaemia (and diabetes mellitus)?
- Polyuria
- Polydipsia
- Unexplained weight loss
- Visual blurring
- Genital thrush
- Lethargy
What are the four ‘pathways’ to diagnose diabetes mellitus?
- Symptoms of hyperglycaemia + one raised venous glucose
- Raised venous glucose on two separate occasions
- Oral glucose tolerance test
- HbA1C 48mmol/L or higher
What are some causes of diabetes mellitus?
- Steroids
- Anti-HIV drugs
- Newer antipsychotics
- Thiazides
- Pancreatic causes
- Cushing’s disease
- Acromegaly
- Phaeochromocytoma
- Hyperthyroidism
- Pregnancy
- Congenital lipodystrophy
- Glycogen storage diseases
Give some steps for the general management of diabetes mellitus.
- Structured educational programme
- Lifestyle advice
- Statins
- Control blood pressure
- Foot care
- Multidisciplinary pregnancy care
- Driving licence authority notification
- Capillary glucose analysis
- Exercise
- Diet
What HbA1C should be aimed for in diabetes mellitus?
Lowest not associated with frequent hypoglycaemia (higher for patients with comorbidities)
Describe the urine albumin:creatinine ratio in diabetic nephropathy.
High
How is impaired glucose tolerance diagnosed?
Fasting plasma glucose <7mmol/L and oral glucose tolerance test 2h glucose above 7.8mmol/L but below 11.1mmol/L
How is impaired fasting glucose diagnosed?
Fasting plasma glucose above 6.1mmol/L but below 7mmol/L.
What is the management of prediabetes?
Lifestyle advice (exercise/diet) and annual review.
What antibodies are associated with type 1 diabetes mellitus?
- anti GAD
- pancreatic islet cell Ab
- Islet antigen-2 Ab
- ZnT8
What are some suggestive features of type 1 diabetes mellitus?
- Onset in childhood/adolescence
- Lean body habitus (weight loss)
- Acute onset of osmotic symptoms
- Prone to ketoacidosis (and urinary ketones)
- High levels of islet antibodies
Which gene determines islet sensitivity to damage?
6q gene
Briefly describe the pathogenesis of type 1 diabetes mellitus.
Insulin deficiency from autoimmune destruction of insulin-secreting pancreatic beta cells.
Failure of insulin secretion leads to breakdown of liver glycogen and unrestrained lipolysis and skeletal muscle breakdown.
What is the treatment for type 1 diabetes mellitus?
Insulin
Give three groups which have a higher prevalence of type 2 diabetes mellitus.
- Asians
- Men
- Elderly
What are some suggestive features of type 2 diabetes mellitus?
- Usually over 30
- Gradual onset
- Family history
Briefly describe the pathogenesis of type 2 diabetes mellitus.
Decreased insulin secretion and increased insulin resistance, which tends to happen because the beta cells are stressed too much.
Which type of diabetes has the stronger genetic influence?
Type 2
What is the treatment for type 2 diabetes?
Metformin, can add sulfonylurea and other pharmacological treatments.
Briefly describe the pathogenesis of diabetic ketoacidosis.
Reduced insulin leads to fat breakdown.
Free fatty acids converted to ketone bodies in liver.
Absence of insulin and increased counterregulatory hormones lead to rising ketones.
Glucose and ketones escape in urine but this leads to osmotic diuresis and falling circulating blood volume.
Ketones also cause anorexia and vomiting.
What are the clinical features of diabetic ketoacidosis?
- Develops over days
- Polyuria/polydipsia
- Nausea/vomiting
- Weight loss
- Weakness
- Abdominal pain
- Drowsiness/confusion
What are the signs of diabetic ketoacidosis?
- Hyperventilation
- Dehydration
- Hypotension
- Tachycardia
- Coma
Describe the biochemistry associated with diabetic ketoacidosis.
- Hyperglycaemia
- High serum potassium (but low overall potassium)
- Low bicarbonate
- Raised urea and creatinine
- Raised blood and urinary ketones
What are the three criteria for a diagnosis of diabetic ketoacidosis?
- Hyperglycaemia (diabetes)
- Raised plasma ketones
- Metabolic acidosis
What are some causes of diabetic ketoacidosis?
- Unknown
- Recurrent illness (infection/MI)
- Treatment errors
- Undiagnosed diabetes
What is the management for diabetic ketoacidosis?
- Rehydration
- Insulin
- Replacement of electrolytes
- Treat underlying cause
What are some complications of diabetic ketoacidosis?
- Cerebral oedema (children)
- Respiratory distress syndrome (adults)
- Thromboembolism
- Aspiration pneumonia
- Death
In which type of diabetes does hyperglycaemic hyperosmolar state usually occur?
Type 2
What are the clinical features of hyperglycaemic hyperosmolar state?
- Longer history (>1 week)
- Dehydration
- Glucose >35mmol/L
- Osmolality >340mmol/Kg
What is the management of hyperglycaemic hyperosmolar state?
- Rehydrate slowly
- Replace electrolytes
- Only use insulin if blood glucose not falling
- Treat cause
Define hypoglycaemia.
Low plasma glucose causing impaired brain function (neuroglycopenia).
What is hypoglycaemia usually caused by?
- High levels of insulin
What causes the symptoms of hypoglycaemia?
Release of glucagon and adrenaline.
What is the difference between mild and severe hypoglycaemia?
Mild is self-treated.
Severe requires help for recovery.
Describe the alert value (level 1) of hypoglycaemia.
Mild
No symptoms
<3.9mmol/L
Describe the serious biochemical (level 2) stage of hypoglycaemia.
- Mild or severe
- <3.0mmol/L
Briefly describe the pathogenesis of hypoglycaemia.
Loss of protective mechanisms against hypoglycaemia in diabetes.
(Bolus insulin cannot be switched off if glucose becomes low, no cross communication between islet cells, lower threshold for adrenaline release)
What are the symptoms of hypoglycaemia?
- Trembling
- Palpitations
- Sweating
- Anxiety
- Hunger
- Nausea
- Headache
- Difficulty concentrating
- Confusion
- Weakness
- Drowsiness
- Dizziness
- Vision changes
- Difficulty speaking
At what blood glucose concentration do symptoms of hypoglycaemia usually start appearing?
3.2-3.0mmol/L
What are the risk factors for hypoglycaemia in type 1 diabetes?
- History of episodes
- HbA1C below 48mmol/L
- Long duration
- Renal impairment
- Impaired awareness of hypo
- Extremities of age
What are the risk factors for hypoglycaemia in type 2 diabetes?
- Advancing age
- Cognitive impairment
- Depression
- Aggressive treatment
What are the consequences of hypoglycaemia?
- Cognitive dysfunction
- Seizures
- Coma
- Accidents
- Employment
- Fear
- Quality of life
What is the treatment for hypoglycaemia?
- Recognise symptoms
- Confirm need for treatment
- Treat 15g fast acting carbs
- Retest
- Eat long acting carbs
Briefly describe the pathogenesis of Conn’s syndrome.
Aldosterone-producing adenoma which causes primary hyperaldosteronism.
What are the clinical features of Conn’s syndrome?
- Hypertension
- Hypokalaemia
- Alkalosis
- Sodium slightly raised or normal
What are the symptoms of Conn’s syndrome?
- Often asymptomatic or signs of hypokalaemia
- Weakness
- Cramps
- Paraesthesiae
- Polyuria
- Polydipsia
- Sometimes increased BP
What are the consequences of Conn’s syndrome?
- Increased sodium and water retention
- Decreased renin release
Which tests should be performed if Conn’s syndrome is suspected?
- U and E
- Renin
- Aldosterone
- Diuretics, hypotensives, steroids, potassium, and laxatives could affect tests
What is the treatment for Conn’s syndrome?
- Laparoscopic adrenalectomy
When does hyperkalaemia need urgent treatment?
Plasma potassium >6.5mmol/L
Why can hyperkalaemia be an emergency?
Could cause myocardial hyperexcitability, leading to ventricular fibrillation and cardiac arrest.
What are the signs/symptoms of hyperkalaemia?
- Fast irregular pulse
- Chest pain
- Weakness
- Palpitations
- Light headedness
What ECG changes occur with hyperkalaemia?
- Tall tented T waves
- Small P waves
- Wide QRS complex
- Ventricular fibrillation
What can cause false results when testing for hyperkalaemia?
- Haemolysis (difficult venipuncture, clenched fist)
- Contamination with potassium EDTA in FBC bottles
- Thrombocytopenia
- Delayed analysis
What are the causes of hyperkalaemia?
- Oliguric renal failure
- K+-sparing diuretics
- Rhabdomyolysis
- Metabolic acidosis
- Excess K+ therapy
- Addison’s disease
- Massive blood transfusion
- Burns
- Drugs (ACEi, suxamethonium)
What is the treatment for hyperkalaemia in a non-urgent case?
- Treat underlying cause
- Review medications
- Polystyrene sulfonate resin
When does hypokalaemia need urgent treatment?
Plasma potassium <2.5mmol/L
Why can hypokalaemia be an emergency?
It can exacerbate digoxin toxicity.
What are the signs/symptoms of hypokalaemia?
- Muscle weakness
- Hypotonia
- Hyporeflexia
- Cramps
- Tetany
- Palpitations
- Light-headedness
- Arrhythmias
- Constipation
What are the ECG changes associated with hypokalaemia?
- Small/inverted T waves
- Prominent U waves
- Long PR interval
- Depressed ST segments
What are the causes of hypokalaemia?
- Diuretics
- Vomiting/diarrhoea
- Pyloric stenosis
- Rectal villous adenoma
- Intestinal fistula
- Cushing’s syndrome/steroids/ACTH
- Conn’s syndrome
- Alkalosis
- Purgative and liquorice abuse
- Renal tubular failure
What is the treatment for mild hypokalaemia?
- Oral potassium supplement
- Review potassium after 3 days
What is the treatment for severe hypokalaemia?
- IV potassium continuously
- Do not give potassium if oligouric
What is another name for neuroendocrine tumours?
Carcinoid tumours
Are neuroendocrine tumours benign or malignant?
They can be either
Describe the typical growth rate of a neuroendocrine tumour.
Tend to be slow growing
Where is the more common place for a neuroendocrine tumour to grow?
Bowel or appendix
Name some less common sites that neuroendocrine tumours can grow.
- Stomach
- Pancreas
- Lung
- Breast
- Kidney
- Ovaries
- Testicles
Name some neuroendocrine tumours of the pancreas.
- Insulinoma
- Gastrinoma
- Glucagonoma
- VIPoma
- Somatostatinoma
Name eight types of neuroendocrine tumours.
- NETs of the gut
- NETs of the pancreas
- NETs of the lung
- Medullary thyroid tumours
- Merkel cell cancer (skin)
- Pituitary gland tumours
- Parathyroid gland tumours
- Adrenal gland tumours
What are the treatment options for neuroendocrine tumours?
Surgery, chemotherapy, and drug treatment to control symptoms.
Give four risk factors for developing a neuroendocrine tumour.
- Multiple endocrine neoplasia type 1 (MEN1)
- Neurofibromatosis type 1
- Von Hippel-Lindau syndrome (VHL)
- Family history
What is carcinoid syndrome?
Symptoms produced by excess hormone production of a neuroendocrine tumour.
What are some symptoms of carcinoid syndrome?
- Diarrhoea
- Abdominal pain
- Loss of appetite
- Flushing
- Tachycardia
- Shortness of breath
- Wheezing
Name the type of acne which is commonly known as ‘teenage acne’.
Acne vulgaris
Define Acne vulgaris.
A disorder of the pilosebaceous follicles in the face and upper trunk.
Describe the three steps in the pathogenesis of acne vulgaris.
- Enlarged sebaceous glands (androgens increase sebum production)
- Abnormal keratinisation of the follicle (glands become blocked)
- Propionibacterium acnes colonises follicles
What is nodulocystic acne?
Severe acne with cysts
What is Acne excoriee?
Acne characterised by self-inflicted wounds, mainly affects young women.
What is infantile acne?
Acne which occurs in infants and neonates
What causes acne mechanica?
Pressure, friction, or rubbing from clothing.
What is acne conglobate?
Severe form of nodulocystic acne with inflammatory lesions that often form exudates or bleed.
What is acne cosmetica caused by?
Contact comedogenic products with the skin.
What is acne fulminans?
Sudden severe inflammatory reaction which causes deep ulcerations and erosions.
What causes chloracne?
Occupational exposure to halogenated hydrocarbons.
What are the risk factors for developing acne?
- Genetic factors
- Boys > girls
- Adolescence
- Premenstrual
- PCOS
- Testosterone replacement
- Anabolic steroids
- Cushing’s disease
What is the presentation of acne?
- Greasy skin
- Comedones/papules/pustules
- Affects face, back, and chest
What are some treatment options for acne?
- Usually self-limiting
- Laser light
- Salicylic acid
- Azelaic acid
- Benzoyl peroxide
- Topical/oral antibiotics
- Topical retinoids/oral isotretinoin
- Anti-androgen treatment
Briefly describe the three steps in the pathogenesis of eczema.
- Reduced lipid barrier of skin (water loss and dry skin)
- Allergens penetrate skin and cause inflammatory response under skin
- Genetic changes inhibit filaggrin production
What are the symptoms of eczema?
- Dry skin
- Red and inflamed skin (commonly next to skin creases)
- Itchy skin
- Skin may become thickened
- Blistered/weepy skin
- Some areas can become infected
Describe the treatment for eczema.
- Avoid irritants and triggers
- Emollients to prevent inflammation (every day)
- Topical steroids (when inflammation flares up)
Briefly describe the pathogenesis of psoriasis.
- Potentially an autoimmune disease
- High turnover of skin epithelia
- Inflamed skin
How does psoriasis typically develop?
As patches (plaques) of red, scaly skin.
How do the plaques usually appear in chronic plaque psoriasis?
Pink or red with overlying flaky, silvery-white scales.
Where does chronic plaque psoriasis usually affect?
Over elbows and knees, and lower back.
Where does pustular psoriasis usually effect?
Palms of hands and soles of feet.
How does the skin appear in pustular psoriasis?
Skin develops crops of pustules.
How does guttate (drop) psoriasis develop?
Triggered by a bacterium after a sore throat.
How does erythrodermic psoriasis present?
Widespread redness of much of the skin surface.
Painful and patient may have fever.
Which type of psoriasis is the most serious?
Erythrodermic psoriasis (requires admission to hospital)
What are some treatments for psoriasis.
- Some don’t require treatment
- Avoid triggers
- Emollients
- Vitamin D based treatments
- Topical steroids
- Coal tar preparations
- Dithranol
- Salicylic acid
- Tazarotene
What are some triggers for psoriasis?
- Stress
- Smoking
- Obesity
- Alcohol
- Infections
- Medication
- Trauma
- Sunlight
- Hormonal changes
Name the three types of skin cancer.
- Malignant melanoma
- Squamous cell cancer
- Basal cell carcinoma
Which group of patients is commonly affected by malignant melanoma?
Younger patients
Give a major cause of malignant melanoma.
Short periods of intense UV exposure.
Describe superficial spreading melanomas.
Percentage, growth rate, metastasis, prognosis
- Account for 70% of malignant melanomas
- Grow slowly
- Metastasise later
- Good prognosis
Describe nodular melanomas.
Percentage, invasion, metastasis, melanin status
- Account for 10-15% of malignant melanomas
- Invade deeply
- Metastasise early
- May be amelanotic
Where do acral melanomas occur?
Palms, soles, and subungual areas.
What does lentigo maligna melanoma evolve from?
Pre-existing lentigo maligna.
What are three major signs of malignant melanoma?
- Change in size
- Change in shape
- Change in colour
What are three minor signs of malignant melanoma?
- Inflammation/crusting/bleeding
- Sensory change
- Diameter >7mm
What are four less helpful signs of malignant melanoma?
- Asymmetry
- Irregular colour
- Elevation
- Irregular border
What is the ABCDE for diagnosis of melanoma?
- Asymmetry
- Border (irregular)
- Colour (non-uniform)
- Diameter (>7mm)
- Elevation
What is the treatment for malignant melanoma?
- Urgent excision can be curative
- Chemotherapy gives response in 10-30%
How does squamous cell cancer usually present?
Ulcerated lesion with hard, raised edges in sun-exposed sites
Give three sites where squamous cell cancer may begin.
- In solar keratoses
- On lips of smokers
- In long-standing ulcers
What are solar keratoses?
Rough patches of skin from long-term sun exposure.
They have crumbly, yellow-white crusts.
Describe local destruction and metastases in squamous cell cancer.
- Local destruction may be extensive
- Metastases to lymph nodes are rare
What is the treatment for squamous cell cancer?
Excision and radiotherapy
What is another name for basal cell carcinoma?
Rodent ulcer
How does a nodular basal cell carcinoma typically look?
Pearly nodule with tiny blood vessels on face or sun-exposed site.
May have central ulcer.
How does a superficial basal cell carcinoma usually appear?
Lesions appear as red, scaly plaques with a raised, smooth edge.
Often on trunk or shoulders.
Describe the metastasis status in basal cell carcinoma.
Metastases are very rare.
What are the complications if a basal cell carcinoma is left untreated?
Slowly causes local destruction.
What is the treatment for basal cell carcinomas?
- Excision
- Cryotherapy
- Topical flurouracil or imiquimod for superficial carcinomas
Name two premalignant skin lesions.
- Solar keratoses
- Bowen’s disease
How does the skin appear in Bowen’s disease?
Slow-growing red/brown scaly plaque.
What can Bowen’s disease progress to?
Squamous cell carcinoma.
What is an ulcer?
An abnormal break in an epithelial or mucosal surface.
What factors should be examined when examining an ulcer?
- Site
- Number
- Surface area
- Depth
- Edge
- Base
- Discharge
- Lymphadenopathy
- Sensation
- Healing
- Temperature
- Shape
What tests should be performed for a skin ulcer?
Skin and ulcer biopsy.
What is the management for skin ulcers?
Treat causes and focus on prevention.
How do venous ulcers develop?
Persistent high pressures in the veins damage the skin.
Can be due to venous insufficiency
How do arterial ulcers develop?
Reduction in arterial blood flow leads to decreased perfusion and poor healing.
How does a neuropathic ulcer occur?
Loss of protective sensation as a result of peripheral neuropathy.
How does an infective ulcer occur?
As the result of an infection.
How do traumatic ulcers occur?
Repetitive damage as a result of trauma.
How do vasculitic ulcers occur?
Due to inflammation of the blood vessels.
What is cellulitis?
Acute, painful, and potentially serious infection of the dermis and subcutaneous tissues.
Which types of bacteria most commonly cause cellulitis?
Streptococcus or Staphylococcus
Describe the borders in cellulitis.
Poorly demarcated.
What is erysipelas?
A superficial form of cellulitis.
What are some risk factors for cellulitis?
- Diabetes
- Cancer
- Immunodeficiency
- Previous cellulitis
- Venous insufficiency
- Elderly age
- Alcoholism
- IV drug use
- Lymphoedema
- Obesity
- Athlete’s foot
- Skin abrasions
- Insect bites
- Pregnancy
Describe the presentation of cellulitis.
- More commonly in lower limbs
- Usually affects one limb
- Usually an obvious precipitating skin lesion
- Erythema, pain, swelling, warmth
- Oedema of affected skin
- Blisters and bullae may form
- Systemic symptoms (fever, malaise)
- Red streaks away from cellulitic area
What do red streaks away from the cellulitic area in cellulitis indicate?
Progression into the lymphatic system.
What is the management of cellulitis?
- Rest
- Elevation
- Analgesia
- Flucloxacillin antibiotics (erythromycin if penicillin allergy)
- Other antibiotics can be used
What is necrotising faciitis.
Rapidly progressive infection of the deep fascia causing necrosis of subcutaneous tissue.
How does necrotising faciitis usually present?
Intense pain over infected skin and underlying muscle.
Patients are systemically ill.
What is the major cause of necrotising faciitis?
Group A b-haemolytic streptococci (but infection is often polymicrobial)
What is the treatment for necrotising faciitis?
- Radical debridement (removal of damaged tissue)
- Potentially amputation
- IV antibiotics
Name two types of non-invasive breast cancer.
Which is more common?
- Non-invasive ductal carcinoma in situ (more common)
- Non-invasive lobular carcinoma in situ
Name eight malignant types of breast cancer.
- Invasive ductal carcinoma
- Invasive lobular carcinoma
- Medullary cancer
- Colloid/mucoid cancer
- Papillary cancer
- Tubular cancer
- Adenoid-cystic
- Paget’s
Which is the most common type of malignant breast cancer?
Invasive ductal carcinoma
Which type of breast cancer tends to affect younger patients?
Medullary cancer
Which type of breast cancer tends to affect elderly patients?
Colloid/mucoid cancer
What does the triple assessment of breast lumps involve?
- Clinical examination
- Histology/cytology
- Mammography/ultrasound
What investigations should be carried out to stage breast cancer?
- CXR
- Bone scan
- Liver UUS/CT/MRI/PET-CT
- LFTs
- Calcium
Describe stage 1 breast cancer.
Confined to breast, mobile.
Describe stage 2 breast cancer.
Growth confined to breast, mobile, lymph nodes in ipsilateral axilla.
Describe stage 3 breast cancer.
- Tumour fixed to muscle (but not chest wall)
- Ipsilateral lymph nodes matted and may be fixed
- Skin involvement larger than tumour
Describe stage 4 breast cancer.
- Complete fixation of tumour to chest wall
- Distant metastases
What factor gives a better prognosis in breast cancer?
Oestrogen receptor positive
Approximately what percentage of breast cancers are oestrogen receptor positive?
60-70%
Give a factor in breast cancer which is associated with aggressive disease and poor prognosis.
Over-expression of HER2 (growth factor receptor gene).
Approximately what percentage of breast cancers over express HER2?
30%
What are the four steps of the treatment of stage 1-2 breast cancer?
- Surgery
- Radiotherapy
- Chemotherapy
- Endocrine agents
What is the aim of endocrine agents in treating breast cancer?
Decrease oestrogen activity
Give four endocrine agents/treatments that are used in oestrogen receptor positive breast cancers.
- Tamoxifen
- Aromatase inhibitors
- Ovarian ablation
- GnRH analogues
Give two treatments used for bone metastases in breast cancer.
- Radiotherapy
- Bisphosphonates
Give eight signs/symptoms of breast cancer.
- Change in size or shape
- Redness or rash
- Discharge
- Swelling in armpit/collarbone
- Lump/thickening
- Change in skin texture
- Nipple inversion
- Constant pain in breast/armpit
What is amyloidosis?
A group of disorders characterised by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation.
Give three conditions that amyloidosis is a feature of.
- Alzheimer’s disease
- Type 2 diabetes mellitus
- Haemodialysis-related amyloidosis
Give the steps in the pathogenesis of primary amyloidosis.
- Proliferation of plasma cell clones
- Amyloidogenic monoclonal immunoglobulins
- Fibrillar light chain protein deposition
- Organ failure
- Death
Give three conditions that primary amyloidosis is associated with.
- Myeloma
- Waldenstrom’s macroglobulinaemia
- Lymphoma
Give five organs that can be affected by amyloidosis.
- Kidneys
- Heart
- Nerves
- Gut
- Vascular
Give three consequences of amyloidosis affecting the kidney.
- Glomerular lesions
- Proteinuria
- Nephrotic syndrome
Give three consequences of amyloidosis affecting the heart.
- Restrictive cardiomyopathy
- Arrhythmias
- Angina
Give two consequences of amyloidosis affecting the nerves.
- Peripheral and autonomic neuropathy
- Carpel tunnel syndrome
Give seven consequences of amyloidosis affecting the gut.
- Macroglossia
- Malabsorption
- Weight loss
- Perforation
- Haemorrhage
- Obstruction
- Hepatomegaly
Give a consequence of amyloidosis affecting the vascular system.
Purpura (especially periorbital)
Give two treatment options for primary amyloidosis.
- Oral melphalan + prednisolone (chemotherapy + steroid)
- Potentially blood stem cell transplant
Briefly describe the pathogenesis of secondary amyloidosis.
Amyloid derived from serum amyloid A (an acute phase protein).
When does secondary amyloidosis occur?
In chronic inflammation and infections.
Name three organs involved in secondary amyloidosis.
- Kidneys
- Liver
- Spleen
Describe the presentation of secondary amyloidosis.
- Proteinuria
- Nephrotic syndrome
- Hepatosplenomegaly
- NOT macroglossia
- Cardiac involvement rare
What is the treatment for secondary amyloidosis?
Treat underlying condition
Briefly describe the pathogenesis of familial amyloidosis.
Autosomal dominant mutation in transthyretin transport protein produced by the liver.
Describe the presentation of familial amyloidosis.
Sensory or autonomic neuropathy with/without cardiac and renal involvement.
What can be done to potentially cure familial amyloidosis?
Liver transplant
How is amyloidosis diagnosed?
Biopsy of affected tissue
What is the median survival time in amyloidosis?
1-2yrs
Define lymphoedema.
Chronic condition that causes swelling in the body’s tissues, which usually develops in the arms or legs. Due to an abnormal collection of protein-rich fluid in the interstitium resulting from obstruction of lymphatic drainage.
Briefly describe the pathophysiology of primary lymphoedema.
Faulty lymphatic drainage due to mutations in genes responsible for the development of the lymphatic system.
What is secondary lymphoedema?
When the lymphatic system has previously been working but becomes damaged.
Give nine causes of secondary lymphoedema.
- Cancer surgery
- Radiotherapy
- Infections (cellulitis)
- Filariasis
- Inflammation
- Venous diseases
- Obesity
- Trauma/injury
- Immobility
What are the symptoms of lymphoedema?
- Swelling in limbs (or other body parts)
- Achy/heavy feeling
- Difficulty with movement
- Repeated skin infections
- Hard, tight skin
- Folds developing in the skin
- Wart-like growths on skin
- Fluid leaking through skin
How is diagnosis of lymphoedema usually made?
History and clinical examination
Give the four components of decongestive lymphatic therapy for lymphoedema.
- Compression bandages
- Skin care
- Exercises
- Specialised massage techniques
Give three surgical interventions that are sometimes used to treat lymphadenopathy.
- Debulking (removal of excess skin and underlying tissue)
- Liposuction (removal of fat from affected tissue)
- Lymphaticovenular anastomosis (connecting lymphatic system with nearby blood vessels)
Define sarcoma.
A malignant tumour of connective tissue.
What are the two general types of sarcoma?
Which is more common?
- Bone sarcoma
- Soft tissue sarcoma (more common)
Give three types of soft tissue sarcoma.
- Gastrointestinal stromal tumours (GIST)
- Gynaecological sarcomas
- Retroperitoneal sarcomas
Give four diagnostic methods for sarcomas.
- Clinical examination
- X-ray/CT/endoscopic ultrasound/PET/MRI
- Biopsy
- Bone scan
What are the three treatment options for sarcomas?
Which is the first treatment?
- Surgery (first treatment)
- Radiotherapy
- Chemotherapy
When is chemotherapy usually used to treat sarcomas?
Used to treat bone sarcomas before or after surgery.
Describe the prognosis in sarcomas.
- 78% live up to one year
- Average percentage of people living three years is 64.5%
- Five year survival rate is 55%
Describe a stage 1 sarcoma.
- Low grade
- Small (<5cm)
- Not spread
Describe stage 2 sarcoma.
- Cancer of any grade (usually larger than grade one)
- Not spread to other parts of the body
Describe stage 3 sarcoma.
- High grade
- Not spread
Describe stage 4 sarcoma.
- Any grade or size
- Spread to other parts of the body
Give three ‘positive’ risk factors for IHD.
- Fruit/veg
- Exercise
- Moderate alcohol
What is angina pectoris?
A symptom which occurs as a consequence of restricted coronary blood flow.
Briefly describe the pathophysiology of angina pectoris.
Microvascular vessels cannot lower resistance enough to compensate for the high resistance in the epicardial arteries, so there is a supply/demand mismatch during exercise.
What are three mechanisms that can cause stable angina pectoris?
- Impairment to blood flow by proximal artery stenosis
- Increased distal resistance (left ventricular hypertrophy)
- Reduced oxygen-carrying capacity of blood (anaemia)
What causes Prinzmetal’s angina?
Coronary spasm
What causes microvascular angina?
Syndrome X
What issues with supply can precipitate angina?
- Anaemia
- Hypoxaemia
- Polycythemia
- Hypothermia
- Hypovolaemia
- Hypervolaemia
What issues with demand can precipitate angina?
- Hypertension
- Tachyarrhythmia
- Valvular heart disease
- Hyperthyroidism
- Hypertrophic cardiomyopathy
- Cold weather
- Heavy metals
- Emotional stress
Describe the three characteristics of anginal chest pain.
- Heavy, central, tight, radiation to arms/jaw/neck
- Precipitated by exertion
- Relieved by rest/GTN
Give nine differential diagnoses of angina.
- Pericarditis
- Myocarditis
- Pulmonary embolism
- Pleurisy
- Chest infection
- Dissection of aorta
- Gastro-oesophageal (reflux, spasm, ulceration)
- Musculo-skeletal
- Psychological
Describe the investigations often used for angina pectoris.
- Examination normal
- ECG normal
- Echo normal
- Anatomical tests
- Physiological tests
Give two anatomical tests that can be used to diagnose angina.
- CT angiography
- Invasive angiography
Give four physiological tests that can be used to diagnose angina.
- Exercise stress treadmill
- Stress echo
- Nuclear perfusion (SPECT)
- Stress MRI
Give five methods of primary prevention of angina.
- Antihypertensives
- Statins
- Diabetic therapy
- Smoking cessation
- General dietary/exercise advice
Give five categories of medication that can be used to treat angina.
- betablockers
- Nitrates
- Calcium channel antagonists
- Antiplatelets
- Statins
What are two revascularisation techniques that can be used in IHD?
- Percutaneous coronary intervention (PCI)
- Coronary artery bypass graft (CABG)
Name three acute coronary syndromes.
- Unstable angina
- Non ST elevation myocardial infarction (NSTEMI)
- ST elevation myocardial infarction (STEMI)
What three characteristics can appear in unstable angina?
- Cardiac chest pain at rest
- Cardiac chest pain with crescendo pattern
- New onset angina
How is unstable angina diagnosed?
- History
- ECG
- No significant rise in troponin
When is the diagnosis of an NSTEMI made?
Usually retrospectively after troponin results and other investigations.
What long term ECG changes occur after a STEMI?
Pathological Q waves
What are the characteristics of cardiac chest pain associated with an acute myocardial infarction?
- Unremitting
- Usually severe (may be mild or absent)
- Occurs at rest
- Associated with sweating, breathlessness, nausea and/or vomiting
Give three groups of patients in which cardiac chest pain associated with an acute MI may be atypical.
- Elderly
- Women
- Diabetics
What is Levine’s sign?
Patient puts fist to their chest (indicates cardiac chest pain)
What are the four major management points for an acute MI?
- Morphine
- Oxygen
- Nitrates
- Aspirin
How can troponin be used in diagnosis of an MI?
Troponin is sensitive but not specific.
If raised after 6 hours, and then significant rise/fall after a further 3 hours, MI is confirmed.
Give five mechanisms that can cause an acute MI.
- Rupture of atherosclerotic plaque (arterial thrombosis)
- Coronary vasospasm
- Drug abuse (amphetamines, cocaine)
- Dissection of coronary artery
- Thoracic aortic dissection
What is the pathophysiological difference between a STEMI and an NSTEMI?
STEMI = complete occlusion of artery NSTEMI = severe narrowing of artery
In which site are DVTs most clinically important and why?
Between the knee and hip are most important because the 6 veins from the calf join to form one large vein.
This means that a larger clot can form, leading to larger emboli.
What are eight risk factors for DVT?
- Age
- Surgery/immobility/leg fracture
- Cancer
- Obesity
- Oestrogen (OC, HRT)
- Pregnancy
- Long haul flights
- Inherited thrombophilia
Why is a clinical diagnosis of DVT unreliable?
Symptoms and signs are non-specific.
What are the symptoms of DVT?
Pain and swelling (usually in calf)
What are the signs of DVT?
- Tenderness
- Swelling
- Warmth
- Discolouration
- Mild fever
- Pitting oedema
How can D-dimer be used in the diagnosis of DVT?
Normal excludes diagnosis but positive is not specific for disease.
Give six conditions which will result in an increased D dimer.
- Surgery
- Pregnancy
- Infection
- Inflammation
- Malignancy
- DVT
How can a DVT be diagnosed?
Ultrasound compression test on proximal veins.
What is the treatment for DVT?
- Low molecular weight heparin
- Oral warfarin or DOAC
- Compression stockings
- Treat underlying cause
Give four methods of mechanical prevention of DVT.
- Hydration
- Early mobilisation
- Compression stockings
- Foot pumps
Give a chemical method of prevention for DVT.
Low molecular weight heparin.
What are the signs of a pulmonary embolism?
- Hypotension
- Cyanosis
- Tachycardia
- Tachypnoea
- Pleural rub
- Severe dyspnoea
- Right heart strain/failure
- Signs/symptoms of DVT
What are the symptoms of pulmonary embolism?
- Breathlessness
- Pleuritic chest pain
Give six differential diagnoses of pulmonary embolism.
- Musculoskeletal
- Infection
- Malignancy
- Pneumothorax
- Cardiac causes
- GI causes
Describe the investigations usually done for a pulmonary embolism.
- CXR usually normal
- ECG sinus tachy (other sings nonconclusive)
- Blood gases (type 1 resp failure)
- Normal D dimer excludes diagnosis
- Ventilation/perfusion scan (rare)
- CTPA (CT pulmonary angiogram) spiral CT with contrast
What is the treatment for a pulmonary embolism?
- Ebolectomy (rare)
- Same as DVT
- Thrombolysis (mechanical or chemical)
- If cannot anticoagulate consider IVC filter
- Ensure normal Hb, platelets, renal function, baseline clotting
What is heart failure?
A complex clinical syndrome of systems and signs that suggest that the efficiency of the heart as a pump is impaired.
What is the definition of heart failure?
Cardiac output is inadequate for the body’s requirements.
What causes congestion in heart failure?
RAAS and sympathetic nervous system activated due to decreased cardiac output.
What is systolic heart failure?
Inability of the ventricle to contract normally, resulting in decreased cardiac output.
What is the typical ejection fraction in systolic heart failure?
<40%
What is another name for systolic heart failure?
Heart failure with reduced ejection fraction.
Give three causes of systolic heart failure.
- IHD
- Myocardial infarction
- Cardiomyopathy
What is diastolic heart failure?
- Inability of the ventricle to relax and fill normally.
Describe the ejection fraction in diastolic heart failure.
> 50%
Give four causes of diastolic heart failure.
- Constrictive pericarditis
- Cardiac tamponade
- Restrictive cardiomyopathy
- Hypertension
Give another name for diastolic heart failure.
Heart failure with preserved ejection fraction.
Give three causes of right ventricular failure.
- Left ventricular failure
- Pulmonary stenosis
- Lung disease
What are the symptoms of left ventricular failure?
- Dyspnoea
- Poor exercise tolerance
- Fatigue
- Orthopnoea
- Paroxysmal nocturnal dyspnoea
- Nocturnal cough
- Wheeze
- Nocturia
- Cold peripheries
- Weight loss
- Muscle wasting
What are the symptoms of right ventricular failure?
- Peripheral oedema
- Ascites
- Nausea
- Anorexia
- Facial engorgement
- Pulsation in face and neck
- Epistaxis (nose bleed)
Describe acute heart failure.
New onset or decompensation of chronic heart failure.
What are the causes of low-output heart failure?
- Systolic/diastolic heart failure
- Decreased heart rate
- Negatively inotropic drugs
- Mitral regurgitation
- Fluid overload
- Aortic stenosis
- Hypertension
What is high-output cardiac failure?
Output normal or increased but fails to meet hugely increased needs.
What are some causes of high-output heart failure?
- Anaemia
- Pregnancy
- Hyperthyroidism
- Paget’s disease
- Arteriovenous malformation
- Beriberi
What are the major criteria for diagnosis of heart failure?
- Paroxysmal nocturnal dyspnoea
- Crepitations
- S3 gallop
- Cardiomegaly
- Increased central venous pressure
- Weight loss or increase (due to fluid retention)
- Neck vein distension
- Acute pulmonary oedema
- Hepatojugular reflux
What are the minor criteria for diagnosis of heart failure?
- Bilateral ankle oedema
- Dyspnoea on ordinary exertion
- Tachycardia
- Nocturnal cough
- Hepatomegaly
- Pleural effusion
- Decrease in vital capacity
How many of each criteria are needed for a diagnosis of heart failure?
2 Major
Or
2 minor + 1 major
What are some other signs of heart failure?
- Exhaustion
- Cool peripheries
- Cyanosis
- Decreased blood pressure
- Narrow pulse pressure
- Pulsus alternans
- Displaced apex
- RV heave
- Murmurs
- Wheeze
- Raised JVP
- Ascites
What investigations can rule out heart failure?
- ECG and B-type natriuretic peptide normal
What can a chest X ray show in heart failure?
- Cardiomegaly
- Prominent upper lobe veins
- Peribronchial cuffing
- Interstitial/alveolar shadowing
- Perihilar ‘Bat’s wing’ shadowing
- Fluid in fissures
- Pleural effusions
- Septal lines
What is the 5 year mortality in heart failure?
75%
Give five methods of pathophysiology of heart failure.
- Ischaemia
- Valvular
- Myopathic
- Hypertensive
- Cor Pulmonale
What is Cor Pulmonale?
Pulmonary hypertension of the lungs which causes right-sided heart failure.
According to NYHA (New York Heart Association), what is Class I heart failure?
No limitation (asymptomatic)
According to NYHA (New York Heart Association), what is Class II heart failure?
Slight limitation (mild HF)
According to NYHA (New York Heart Association), what is Class III heart failure?
Marked limitation (symptomatically moderate HF)
According to NYHA (New York Heart Association), what is Class IV heart failure?
Inability to carry out physical activity without discomfort (symptomatically severe HF)
What is primary hypertension and what percentage of cases does it account for?
Hypertension with no obvious cause.
Accounts for 95%.
What is secondary hypertension and what percentage of cases does it account for?
Hypertension with a known cause.
Accounts for 5% of cases.
What is the cut off measurement for hypertension in the clinic?
140/90mmHg
What is the cut off for hypertension at home?
135/85mmHg
What is stage 1 hypertension and how is it treated?
140/90mmHg - 160/100mmHg
Treated with lifestyle changes
What is stage 2 hypertension and how is it treated?
Above 160/100mmHg.
Treated with medications.
What is malignant hypertension?
Rapid rise in blood pressure leading to vascular damage.
What is a sign of malignant hypertension?
Bilateral retinal haemorrhages and exudates.
What are the symptoms of malignant hypertension?
- Headache
- Visual disturbances
Give some causes of secondary hypertension.
- Renal disease
- Endocrine disease
- Coarctation of aorta
- Pregnancy
- Steroids
- Monoamine oxidase inhibitors (antidepressants)
- Oral contraceptive pill
- Sleep apnoea
- Genetic factors
- Drugs (NSAIDs, cyclosporin, cold spores, recreational drugs)
What are the symptoms of hypertension.
Usually asymptomatic
What tests should be carried out in hypertension.
- Retinal blood vessel examination
- Can test for risks of complications
- Exclude secondary causes
- 24h ambulatory blood pressure monitoring
- Tests for end-organ damage
What would you expect the drop in blood pressure to be on tablets?
10mmHg
What blood pressure should be aimed for when treating hypertension?
140/90mmHg
Lower for diabetics for people with proteinuria.
What are the three major lifestyle changes that can reduce blood pressure?
- Weight loss
- Drink less alcohol
- Reduce salt intake
Give five complications of hypertension.
- Stroke
- IHD
- Renal failure
- Heart failure
- Losing 5 years of life
What is an aneurysm?
A dilation >50% of a blood vessels original diameter.
What is the difference between a true aneurysm and a pseudoaneurysm?
A true aneurysm involves all layers of the vessel wall, whereas a pseudoaneurysm only involves the adventitia.
Describe the pathophysiology of an aortic aneurysm.
Degeneration of elastic lamellae and smooth muscle loss.
Give five causes of an aortic aneurysm.
- Atheroma
- Trauma
- Infection
- Connective tissue disorders
- Inflammatory
Give five complications of an aortic aneurysm.
- Rupture
- Thrombosis
- Embolism
- Fistulae
- Pressure on other structures
Are AAA more common in men or women?
Men
Describe current screening for AAA.
All men screened at age 65.
What are the symptoms of an unruptured AAA?
Often no symptoms, but may cause abdominal or back pain.
Give four risk factors for rupture of an AAA.
- High blood pressure
- Smoker
- Female
- Strong family history
Give the signs/symptoms of a ruptured abdominal aortic aneurysm.
- Intermittent/continuous abdominal pain
- Pain radiates to back, iliac fossae, or groins
- Collapse
- Expansile abdominal mass
- Shock
Describe the management of a ruptured AAA.
- ECG
- Take blood and cross-match
- Catheterise
- IV access
- Treat shock
- Take patient straight to theatre
What is an aortic dissection?
Blood splits the aortic media.
As the dissection expands, branches of the aorta occlude sequentially.
What are the signs/symptoms of an aortic dissection?
Sudden tearing chest pain with or without radiation to the back.
What is a type A aortic dissection?
Dissection involving ascending aorta.
What is a type B aortic dissection?
Dissection not involving ascending aorta.
What are the consequences of aortic dissection?
And which arteries are occluded to cause them?
- Hemiplegia (carotid artery)
- Unequal arm pulses and BP (anterior spinal artery)
- Acute limb ischaemia (anterior spinal artery)
- Paraplegia (anterior spinal artery)
- Anuria (renal artery)
- Aortic valve incompetence
- Inferior myocardial infarction
- Cardiac arrest
Describe the management of an aortic dissection.
- All patients with type A considered for surgery
- Type B may be treated medically before considered for surgery
- Cross match blood
- ECG
- CXR
- CT/MRI
- ITU
- Hypotensives
What is claudication?
A condition in which cramping pain in the leg is induced by exercise.
Briefly describe the pathogenesis of peripheral vascular disease.
Atherosclerosis causing stenosis of the arteries.
What are the symptoms of peripheral vascular disease?
- Cramping in calf, thigh, or buttock after walking for a given distance
- Cramping relieved by rest
What is the distance called that a person with peripheral vascular disease can walk before symptoms appear?
Claudication distance
If the patient suffers cramping in the calf, where is the peripheral vascular disease likely to be?
Femoral
