Phase2a > Diseases > Flashcards

Diseases Flashcards

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1
Q

How is malaria spread?

A

Through the bite of the female anopheles mosquito

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2
Q

Name the five species of protozoa which cause malaria.

A
  • Plasmodium falciparum
  • Plasmodium ovale
  • Plasmodium vivax
  • Plasmodium malariae
  • Plasmodium knowlesi
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3
Q

How is malaria diagnosed?

A
  • Thick blood film to identify disease
  • Thin blood film to identify species
  • Rapid diagnostic tests to detect antigen
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4
Q

What are the symptoms of malaria?

A
  • Fever (usually fluctuating)
  • Chills
  • Headache
  • Myalgia
  • Fatigue
  • Diarrhoea
  • Vomiting
  • Abdominal pain
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5
Q

What are the signs of malaria?

A
  • Anaemia
  • Jaundice
  • Hepaosplenomegaly
  • ‘Black water fever’ - dark urine
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6
Q

Briefly describe the pathophysiology of malaria.

A
  • Sporozoites infect hepatocytes in liver
  • Develops into schizont
  • Schizont bursts and infects red blood cells
  • Schizont forms in red blood cell and bursts
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7
Q

Which plasmodium species can form hypnozoites in the liver which can reactivate malaria?

A
  • Ovale

- Vivax

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8
Q

Which plasmodium species causes complicated malaria?

A

Plasmodium falciparum

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9
Q

Briefly describe the pathophysiology of complicated malaria.

A

Red blood cells have proteinaceous knobs which bind to endothelial cells and obstruct small vessels.

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10
Q

What are the complications of complicated malaria?

A
  • Vascular occlusion and hypoglycaemia in brain
  • Acute respiratory distress syndrome
  • Renal failure
  • Thrombocytopenia and DIC
  • Shock
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11
Q

What is the treatment for uncomplicated malaria?

A

Chloroquine

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12
Q

What is the treatment for complicated malaria?

A
  • Artesunate
    OR
  • Quinine and doxycycline
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13
Q

What are some supportive measures that can be given in complicated malaria?

A
  • Antiepileptics
  • Oxygen
  • Diuretics
  • Ventilation
  • Fluids
  • Dialysis
  • Broad spectrum antibiotics
  • Blood products
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14
Q

What should be given to prevent a malaria relapse?

What precaution should be taken before treatment?

A

Primiquine

Screen for G6PD deficiency)

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15
Q

Name the virus which causes HIV.

A

HIV1

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16
Q

Give five risk factors for having HIV.

A
  • Africa
  • Homosexuality less accepted
  • Men who have sex with men
  • IV drug abusers
  • HIV positive mother
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17
Q

Briefly describe the pathophysiology of HIV.

A
  • HIV gp120 binds to CD4 receptors
  • Cells migrate to lymphoid tissue and virus replicates
  • Virions released from host cell by budding
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18
Q

Describe the seroconversion stage of HIV.

A

Initial stage of the primary infection.

May be accompanied by transient illness after exposure.

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19
Q

Describe the asymptomatic infection in HIV.

A

Battle between the virus and the immune system.

Some people have generalised lymphadenopathy.

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20
Q

What is AIDS-related complex?

A

A stage in the HIV infection where constitutional symptoms develop.

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21
Q

What is AIDS?

A

HIV + an indicator disease

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22
Q

What is the typical time scale from HIV to AIDS?

A

8 years

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23
Q

What symptoms may be experienced in HIV seroconversion?

A
  • Fever
  • Myalgia
  • Pharyngitis
  • Rash
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24
Q

What are the signs of generalised lymphadenopathy?

A

Nodes >1cm in diameter at >2 extra-inguinal sites.

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25
What are the constitutional symptoms experienced in AIDS-related complex?
- High temperature - Night sweats - Diarrhoea - Weight loss - Minor opportunistic infections
26
What symptoms indicate HIV progression?
- Chronic fever - Cough >1month - Chronic diarrhoea - Oral thrush - Weight loss - TB - Herpes zoster
27
How is HIV diagnosed?
Serum HIV antibody
28
When might the HIV antibody test be negative even when the person is infected?
1-3 weeks after exposure
29
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
30
Give three techniques to prevent HIV.
- Blood screening - Disposable equipment - Antenatal antiretrovirals if HIV +ve mother
31
What is HAART?
Highly active antiretroviral therapy
32
How many drugs, and what types should be used in HAART?
At least 3 drugs. | NRTI, NRTI, and one other.
33
What are nucleoside reverse transcriptase inhibitors?
Substitute nucleotide bases used to treat HIV.
34
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
35
Why are three different drugs used in HAART?
Monotherapy causes drug resistance by selecting for resistant strain and allowing it to replicate.
36
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
37
What is the most common opportunistic infection in HIV?
Pneumocystis pneumonia
38
What are the criteria for a diagnosis of AIDS?
CD4 count <200 and AIDS defining illness
39
What is the normal CD4 range?
500-1500
40
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.
41
How can alcohol cause a paracetamol overdose?
Alcohol induces the CYP450 which forms NAPQI
42
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
43
What is the treatment for a paracetamol overdose in the last four hours?
Activated charcoal
44
What is the treatment for a paracetamol overdose if ingestion occurred more than four hours ago?
IV N-acetylcysteine
45
Give a definition of sepsis.
Inflammatory response causing damage to tissues of the body.
46
Give the general criteria for diagnosis of sepsis.
Systemic inflammatory response syndrome + presence of an infection
47
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.
48
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
49
What is the management of sepsis?
- Take cultures - Start antibiotics (broad spectrum) - IV fluids - Low dose steroids may improve BP but not mortality
50
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
51
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
52
Define severe sepsis.
Sepsis with evidence of organ hypoperfusion
53
Define septic shock.
Severe sepsis with hypotension
54
What is acromegaly?
Increased secretion of growth hormone from pituitary adenoma.
55
What is the alternative name for acromegaly if it occurs before puberty?
Gigantism
56
Briefly describe the pathogenesis of acromegaly.
Increased rate of bone and soft tissue growth by stimulating secretion of IGF-1.
57
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
58
Describe the rate of symptom onset in acromegaly.
Slow
59
Does acromegaly affect more men or women?
Affects men and women equally
60
What are the symptoms of acromegaly?
- Acroparaesthesia (burning/tingling in peripheries) - Amenorrhoea - Decreased libido - Headache - Increased sweating - Snoring - Arthralgia (joint pain) - Backache
61
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
62
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
63
How can acromegaly be diagnosed?
- Clinical features - GH - IGF-1 - Glucose tolerance test (glucose suppresses GH)
64
What random serum measurements can exclude acromegaly?
- GH <0.4ng/ml | - Normal IGF-1
65
What glucose tolerance test measurements can exclude acromegaly?
- Normal IGF-1 | - GH <1ng/ml
66
What is the treatment for acromegaly?
- Pituitary surgery (mainstay of treatment) - Medical therapy - Radiotherapy
67
What medical therapy can be used to treat acromegaly?
- Dopamine agonists - Somatostatin analogues - Growth hormone receptor antagonists
68
Is prolactinoma more common in men or women?
Women
69
Briefly describe the pathophysiology of prolactinoma.
Lactotroph cell tumour of the pituitary
70
Give two other things, other than prolactinoma, that can cause hyperprolactinaemia.
- Compression of pituitary stalk | - Dopamine antagonists
71
What are the clinical features of prolactinoma?
- Tumour mass effects - Menstrual irregularity/amenorrhoea - Infertility - Galactorrhoea - Low libido - Low testosterone (men)
72
What are the complications of prolactinoma?
- Hypogonadism | - Osteoporosis
73
When will measuring serum prolactin levels cause a false result?
In patients on antidopaminergic drugs
74
How is prolactinoma treated?
Using dopamine agonists
75
Briefly describe the pathogenesis of Cushing’s syndrome.
Excess cortisol
76
What is Cushing’s disease?
Pituitary adenoma secreting ACTH
77
What are five sources of excess cortisol in Cushing’s disease?
- Exogenous steroids - Pituitary adenoma (Cushing’s disease) - Ectopic tumour - Synthetic ACTH - Adrenal tumour
78
What are the symptoms of Cushing’s syndrome?
- Increased weight - Mood change - Proximal weakness - Gonadal dysfunction - Acne - Recurrent Achilles tendon rupture
79
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
80
Why can’t Cushing’s syndrome be diagnosed using random cortisol?
Cortisol is affected by illness, time of day, and stress.
81
How is Cushing’s disease diagnosed?
Overnight dexamethosome suppression test. | Usually suppresses cortisol overnight but doesn’t in Cushing’s syndrome
82
What is the treatment for iatrogenic Cushing’s syndrome?
Ideally stop medications
83
What is the treatment for Cushing’s syndrome caused by any type of tumour?
Surgery
84
What is primary adrenal insufficiency also known as?
Addison’s disease
85
What causes secondary adrenal insufficiency?
- Hypopituitarism | - Steroids (suppression of HPA)
86
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.
87
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
88
What are the signs of adrenal insufficiency?
- Pigmentation and pallor | - Hypotension
89
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
90
What is the biochemistry associated with adrenal insufficiency?
- Low Na, High K - Eosinophilia - Borderline elevated TSH
91
How can adrenal insufficiency be diagnosed?
- 0900 cortisol and ACTH | - Synacthen test (ACTH stimulation test)
92
How can primary and secondary adrenal insufficiency be differentiated using blood tests?
Elevated renin/low aldosterone in primary
93
What is the treatment for adrenal insufficiency?
Hydrocortisone twice or three times daily. | Also replace aldosterone with fludrocortisone in primary.
94
Describe the presentation of adrenal crisis.
- Hypotension and cardiovascular collapse - Fatigue - Fever - Hypoglycaemia - Hyponatraemia and hyperkalaemia
95
Describe the management of adrenal crisis.
- Cortisol/ACTH bloods if possible - Immediate hydrocortisone - Fluid resuscitation - Hydrocortisone 6 hourly - In primary start fludrocortisone
96
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
97
What is thyrotoxicosis?
The clinical effect of excess thyroid hormone.
98
What are the symptoms of hyperthyroidism?
- Diarrhoea - Weight loss - Increased appetite - Over-active - Sweats - Heat intolerance - Palpitations - Tremor - Irritability - Labile emotions - Oligomenorrhoea/infertility
99
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
100
What are the signs of Graves’ disease?
- Eye disease (exophthalmos, ophthalmoplegia) - Pretibial myxoedema - Thyroid acropachy
101
How can hyperthyroidism be diagnosed?
- TSH low - T3/T4 increased - Check thyroid autoantibodies - Isotope scan if cause is unclear
102
What are the causes of hyperthyroidism?
- Graves’ disease - Toxic multinodular goitre - Toxic adenoma - Ectopic thyroid tissue - Exogenous
103
Briefly describe the pathogenesis of Graves’ disease.
Circulating IgG autoantibodies binding to and activating thyrotropin receptors (TSH-R), causing thyroid enlargement.
104
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.
105
What is the treatment for hyperthyroidism?
- Drugs (b blockers to control symptoms) - Anti-thyroid medication (titration/block and replace) - Radioiodine - Thyroidectomy
106
What are the complications of hyperthyroidism?
- Heart failure - Angina - Thyroid storm - Atrial fibrillation - Osteoporosis - Ophthalmopathy - Gynaecomastia
107
What is the main known risk factor for thyroid eye disease?
Smoking
108
What are the symptoms of thyroid eye disease?
- Eye discomfort - Grittiness - Increased tear production - Photophobia - Diplopia (double vision) - Decreased acuity - Afferent pupillary defect
109
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)
110
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
111
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)
112
How can hypothyroidism be diagnosed?
- Increased TSH - Decreased T4 - Thyroglobulin and thyroid peroxidase (TPO) antibodies (not specific for disease)
113
What are the causes of primary autoimmune hypothyroidism?
- Primary atrophic hypothyroidism | - Hashimoto’s thyroiditis
114
What are the causes of primary hypothyroidism?
- Iodine deficiency - Thyroidectomy - Radioiodine treatment - Drug-induced - Subacute thyroiditis
115
What drugs can cause hypothyroidism?
- Anti-thyroid drugs - Amiodarone - Lithium - Iodine
116
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
117
What is the treatment for hypothyroidism?
Levothyroxine
118
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
119
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
120
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
121
What age range does papillary thyroid cancer commonly occur in?
Younger patients
122
What age range does follicular thyroid cancer usually occur in?
Middle age
123
Which type of thyroid cancer can be part of MEN syndrome?
Medullary thyroid cancer
124
What hormone can medullary thyroid cancers produce?
Calcitonin
125
What is the treatment for medullary thyroid cancer?
Thyroidectomy and node clearance
126
What should be screened for before a thyroidectomy in medullary thyroid cancer?
Phaeochromocytoma
127
Is thyroid lymphoma more common in males or females?
Females
128
How might a patient with thyroid lymphoma present?
- Stridor (high-pitched wheeze) | - Dysphagia (swallowing problems)
129
What is the treatment for thyroid lymphoma?
Chemoradiotherapy
130
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)
131
What is a possible complication of Carbimazole?
Agranulocytosis
132
Why should corrected calcium level always be measured?
Low serum albumin may cause low total serum calcium.
133
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
134
What is Chvostek's sign?
Tap the facial nerve and look for facial muscle spasm.
135
What is Trousseau's sign?
Inflate BP cuff and look for hand spasm.
136
Give three causes of hypocalcaemia.
- Vitamin D deficiency - Hypoparathyroidism - Pseudohypoparathyroidism
137
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
138
What are the signs/symptoms of hypercalcaemia?
- Thirst - Polyuria - Nausea - Constipation - Confusion/coma - Renal stones - Short QT interval
139
Give the two major causes of hypercalcaemia.
- Malignancy | - Primary hyperparathyroidism
140
Give five other causes of hypercalcaemia.
- Thiazide diuretics - Thyrotoxicosis - Sarcoidosis - Adrenal insufficiency - Immobilisation
141
Give three malignancies that can cause hypercalcaemia.
- Bone metastases - Myeloma - Lymphoma
142
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).
143
Briefly describe the pathophysiology of secondary hyperparathyroidism.
Excessive secretion of parathyroid hormone due to hypocalcaemia.
144
Briefly describe the pathophysiology of tertiary hyperparathyroidism.
- Renal failure can’t activate vitamin D - Decreased calcium absorption - Increased PTH causes nodular hyperplasia and autonomy
145
What is the overall effect on serum calcium resulting from tertiary hyperparathyroidism?
Hypercalcaemia
146
What are the four consequences of hyperparathyroidism?
- Bones (osteitis fibrosa cystica, osteoporosis) - Kidney stones - Psychic groans (confusion) - Abdominal moans (constipation and acute pancreatitis)
147
What are some causes of hypoparathyroidism?
- Various syndromes - Developmental abnormality of third and fourth branchial pouches - Genetic - Surgical - Radiation - Autoimmune - Infiltration - Magnesium deficiency
148
Briefly describe the pathophysiology of pseudohypoparathyroidism.
Resistance to parathyroid hormone.
149
Describe what causes pseudohypoparathyroidism.
Type 1(a) Albright hereditary osteodystrophy, which is a mutation with a deficient Ga subunit.
150
What are the signs/symptoms of pseudohypoparathyroidism?
- Short stature - Obesity - Round facies - Mild learning difficulties - Subcutaneous ossification - Short fourth metacarpals - Other hormone resistance
151
What is pseudopseudohypoparathyroidism?
Same clinical phenotype as pseuohypoparathyroidism but with normal calcium metabolism (may have a partial mutation).
152
Describe the PTH, calcium, and phosphate levels in vitamin D deficiency.
High PTH Low Calcium Low phosphate
153
Describe the PTH, calcium, and phosphate levels in hypoparathyroidism.
Low PTH Low calcium High phosphate
154
Describe the PTH, calcium, and phosphate levels in pseudohypoparathyroidism.
High PTH Low calcium High phosphate
155
Describe the PTH, calcium, and phosphate levels in pseudopseudohypoparathyroidism.
Normal PTH Normal calcium Normal phosphate
156
Describe the PTH, calcium, and phosphate levels in hypercalcaemia of malignancy.
Low PTH High calcium Unpredictable phosphate
157
Describe the PTH, calcium, and phosphate levels in primary hyperparathyroidism.
High PTH High calcium Low phosphate
158
Describe the PTH, calcium, and phosphate levels in tertiary hyperparathyroidism.
High PTH High calcium High phosphate
159
What are the symptoms of diabetes insipidus?
- Polyuria - Polydipsia - No glycosuria - Dehydration - Symptoms of hypernatraemia
160
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)
161
Briefly describe the pathophysiology of cranial diabetes insipidus.
Lack of vasopressin
162
What are some causes of cranial diabetes insipidus.
- Idiopathic - Congenital - Tumour - Trauma - Infections - Vascular - Inflammatory
163
How is cranial diabetes insipidus treated?
- Treat any underlying condition | - Desmopressin
164
Briefly describe the pathogenesis of nephrogenic diabetes insipidus.
Resistance to vasopressin action.
165
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)
166
What is the management of nephrogenic diabetes insipidus?
- Try and avoid precipitating drugs - Free access to water - Very high dose desmopressin - Hydrochlorothiazide/indomethacin
167
What is primary polydipsia?
Causes same symptoms as diabetes insipidus but is just excessive thirst with no clear cause.
168
Briefly describe the pathophysiology of syndrome of inappropriate secretion of ADH.
Too much ADH when it should not be being secreted.
169
How does SIADH appear clinically?
Normal circulating volume and no oedema.
170
What are the signs/symptoms of SIADH?
- Low plasma sodium - Low osmolality - Inappropriately concentrated urine - Water retention
171
Give five general causes of SIADH.
- CNS disorders - Tumours - Respiratory causes - Endocrine causes - Drugs
172
What is the management of SIADH?
- Diagnose and treat underlying condition - Fluid restriction - Sometimes demeclocycline - If low sodium and fitting hypertonic saline in ITU
173
What are the symptoms of hyperglycaemia (and diabetes mellitus)?
- Polyuria - Polydipsia - Unexplained weight loss - Visual blurring - Genital thrush - Lethargy
174
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
175
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
176
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
177
What HbA1C should be aimed for in diabetes mellitus?
Lowest not associated with frequent hypoglycaemia (higher for patients with comorbidities)
178
Describe the urine albumin:creatinine ratio in diabetic nephropathy.
High
179
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
180
How is impaired fasting glucose diagnosed?
Fasting plasma glucose above 6.1mmol/L but below 7mmol/L.
181
What is the management of prediabetes?
Lifestyle advice (exercise/diet) and annual review.
182
What antibodies are associated with type 1 diabetes mellitus?
- anti GAD - pancreatic islet cell Ab - Islet antigen-2 Ab - ZnT8
183
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
184
Which gene determines islet sensitivity to damage?
6q gene
185
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.
186
What is the treatment for type 1 diabetes mellitus?
Insulin
187
Give three groups which have a higher prevalence of type 2 diabetes mellitus.
- Asians - Men - Elderly
188
What are some suggestive features of type 2 diabetes mellitus?
- Usually over 30 - Gradual onset - Family history
189
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.
190
Which type of diabetes has the stronger genetic influence?
Type 2
191
What is the treatment for type 2 diabetes?
Metformin, can add sulfonylurea and other pharmacological treatments.
192
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.
193
What are the clinical features of diabetic ketoacidosis?
- Develops over days - Polyuria/polydipsia - Nausea/vomiting - Weight loss - Weakness - Abdominal pain - Drowsiness/confusion
194
What are the signs of diabetic ketoacidosis?
- Hyperventilation - Dehydration - Hypotension - Tachycardia - Coma
195
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
196
What are the three criteria for a diagnosis of diabetic ketoacidosis?
- Hyperglycaemia (diabetes) - Raised plasma ketones - Metabolic acidosis
197
What are some causes of diabetic ketoacidosis?
- Unknown - Recurrent illness (infection/MI) - Treatment errors - Undiagnosed diabetes
198
What is the management for diabetic ketoacidosis?
- Rehydration - Insulin - Replacement of electrolytes - Treat underlying cause
199
What are some complications of diabetic ketoacidosis?
- Cerebral oedema (children) - Respiratory distress syndrome (adults) - Thromboembolism - Aspiration pneumonia - Death
200
In which type of diabetes does hyperglycaemic hyperosmolar state usually occur?
Type 2
201
What are the clinical features of hyperglycaemic hyperosmolar state?
- Longer history (>1 week) - Dehydration - Glucose >35mmol/L - Osmolality >340mmol/Kg
202
What is the management of hyperglycaemic hyperosmolar state?
- Rehydrate slowly - Replace electrolytes - Only use insulin if blood glucose not falling - Treat cause
203
Define hypoglycaemia.
Low plasma glucose causing impaired brain function (neuroglycopenia).
204
What is hypoglycaemia usually caused by?
- High levels of insulin
205
What causes the symptoms of hypoglycaemia?
Release of glucagon and adrenaline.
206
What is the difference between mild and severe hypoglycaemia?
Mild is self-treated. | Severe requires help for recovery.
207
Describe the alert value (level 1) of hypoglycaemia.
Mild No symptoms <3.9mmol/L
208
Describe the serious biochemical (level 2) stage of hypoglycaemia.
- Mild or severe | - <3.0mmol/L
209
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)
210
What are the symptoms of hypoglycaemia?
- Trembling - Palpitations - Sweating - Anxiety - Hunger - Nausea - Headache - Difficulty concentrating - Confusion - Weakness - Drowsiness - Dizziness - Vision changes - Difficulty speaking
211
At what blood glucose concentration do symptoms of hypoglycaemia usually start appearing?
3.2-3.0mmol/L
212
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
213
What are the risk factors for hypoglycaemia in type 2 diabetes?
- Advancing age - Cognitive impairment - Depression - Aggressive treatment
214
What are the consequences of hypoglycaemia?
- Cognitive dysfunction - Seizures - Coma - Accidents - Employment - Fear - Quality of life
215
What is the treatment for hypoglycaemia?
- Recognise symptoms - Confirm need for treatment - Treat 15g fast acting carbs - Retest - Eat long acting carbs
216
Briefly describe the pathogenesis of Conn’s syndrome.
Aldosterone-producing adenoma which causes primary hyperaldosteronism.
217
What are the clinical features of Conn’s syndrome?
- Hypertension - Hypokalaemia - Alkalosis - Sodium slightly raised or normal
218
What are the symptoms of Conn’s syndrome?
- Often asymptomatic or signs of hypokalaemia - Weakness - Cramps - Paraesthesiae - Polyuria - Polydipsia - Sometimes increased BP
219
What are the consequences of Conn’s syndrome?
- Increased sodium and water retention | - Decreased renin release
220
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
221
What is the treatment for Conn’s syndrome?
- Laparoscopic adrenalectomy
222
When does hyperkalaemia need urgent treatment?
Plasma potassium >6.5mmol/L
223
Why can hyperkalaemia be an emergency?
Could cause myocardial hyperexcitability, leading to ventricular fibrillation and cardiac arrest.
224
What are the signs/symptoms of hyperkalaemia?
- Fast irregular pulse - Chest pain - Weakness - Palpitations - Light headedness
225
What ECG changes occur with hyperkalaemia?
- Tall tented T waves - Small P waves - Wide QRS complex - Ventricular fibrillation
226
What can cause false results when testing for hyperkalaemia?
- Haemolysis (difficult venipuncture, clenched fist) - Contamination with potassium EDTA in FBC bottles - Thrombocytopenia - Delayed analysis
227
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)
228
What is the treatment for hyperkalaemia in a non-urgent case?
- Treat underlying cause - Review medications - Polystyrene sulfonate resin
229
When does hypokalaemia need urgent treatment?
Plasma potassium <2.5mmol/L
230
Why can hypokalaemia be an emergency?
It can exacerbate digoxin toxicity.
231
What are the signs/symptoms of hypokalaemia?
- Muscle weakness - Hypotonia - Hyporeflexia - Cramps - Tetany - Palpitations - Light-headedness - Arrhythmias - Constipation
232
What are the ECG changes associated with hypokalaemia?
- Small/inverted T waves - Prominent U waves - Long PR interval - Depressed ST segments
233
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
234
What is the treatment for mild hypokalaemia?
- Oral potassium supplement | - Review potassium after 3 days
235
What is the treatment for severe hypokalaemia?
- IV potassium continuously | - Do not give potassium if oligouric
236
What is another name for neuroendocrine tumours?
Carcinoid tumours
237
Are neuroendocrine tumours benign or malignant?
They can be either
238
Describe the typical growth rate of a neuroendocrine tumour.
Tend to be slow growing
239
Where is the more common place for a neuroendocrine tumour to grow?
Bowel or appendix
240
Name some less common sites that neuroendocrine tumours can grow.
- Stomach - Pancreas - Lung - Breast - Kidney - Ovaries - Testicles
241
Name some neuroendocrine tumours of the pancreas.
- Insulinoma - Gastrinoma - Glucagonoma - VIPoma - Somatostatinoma
242
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
243
What are the treatment options for neuroendocrine tumours?
Surgery, chemotherapy, and drug treatment to control symptoms.
244
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
245
What is carcinoid syndrome?
Symptoms produced by excess hormone production of a neuroendocrine tumour.
246
What are some symptoms of carcinoid syndrome?
- Diarrhoea - Abdominal pain - Loss of appetite - Flushing - Tachycardia - Shortness of breath - Wheezing
247
Name the type of acne which is commonly known as ‘teenage acne’.
Acne vulgaris
248
Define Acne vulgaris.
A disorder of the pilosebaceous follicles in the face and upper trunk.
249
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
250
What is nodulocystic acne?
Severe acne with cysts
251
What is Acne excoriee?
Acne characterised by self-inflicted wounds, mainly affects young women.
252
What is infantile acne?
Acne which occurs in infants and neonates
253
What causes acne mechanica?
Pressure, friction, or rubbing from clothing.
254
What is acne conglobate?
Severe form of nodulocystic acne with inflammatory lesions that often form exudates or bleed.
255
What is acne cosmetica caused by?
Contact comedogenic products with the skin.
256
What is acne fulminans?
Sudden severe inflammatory reaction which causes deep ulcerations and erosions.
257
What causes chloracne?
Occupational exposure to halogenated hydrocarbons.
258
What are the risk factors for developing acne?
- Genetic factors - Boys > girls - Adolescence - Premenstrual - PCOS - Testosterone replacement - Anabolic steroids - Cushing’s disease
259
What is the presentation of acne?
- Greasy skin - Comedones/papules/pustules - Affects face, back, and chest
260
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
261
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
262
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
263
Describe the treatment for eczema.
- Avoid irritants and triggers - Emollients to prevent inflammation (every day) - Topical steroids (when inflammation flares up)
264
Briefly describe the pathogenesis of psoriasis.
- Potentially an autoimmune disease - High turnover of skin epithelia - Inflamed skin
265
How does psoriasis typically develop?
As patches (plaques) of red, scaly skin.
266
How do the plaques usually appear in chronic plaque psoriasis?
Pink or red with overlying flaky, silvery-white scales.
267
Where does chronic plaque psoriasis usually affect?
Over elbows and knees, and lower back.
268
Where does pustular psoriasis usually effect?
Palms of hands and soles of feet.
269
How does the skin appear in pustular psoriasis?
Skin develops crops of pustules.
270
How does guttate (drop) psoriasis develop?
Triggered by a bacterium after a sore throat.
271
How does erythrodermic psoriasis present?
Widespread redness of much of the skin surface. | Painful and patient may have fever.
272
Which type of psoriasis is the most serious?
Erythrodermic psoriasis (requires admission to hospital)
273
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
274
What are some triggers for psoriasis?
- Stress - Smoking - Obesity - Alcohol - Infections - Medication - Trauma - Sunlight - Hormonal changes
275
Name the three types of skin cancer.
- Malignant melanoma - Squamous cell cancer - Basal cell carcinoma
276
Which group of patients is commonly affected by malignant melanoma?
Younger patients
277
Give a major cause of malignant melanoma.
Short periods of intense UV exposure.
278
Describe superficial spreading melanomas. | Percentage, growth rate, metastasis, prognosis
- Account for 70% of malignant melanomas - Grow slowly - Metastasise later - Good prognosis
279
Describe nodular melanomas. | Percentage, invasion, metastasis, melanin status
- Account for 10-15% of malignant melanomas - Invade deeply - Metastasise early - May be amelanotic
280
Where do acral melanomas occur?
Palms, soles, and subungual areas.
281
What does lentigo maligna melanoma evolve from?
Pre-existing lentigo maligna.
282
What are three major signs of malignant melanoma?
- Change in size - Change in shape - Change in colour
283
What are three minor signs of malignant melanoma?
- Inflammation/crusting/bleeding - Sensory change - Diameter >7mm
284
What are four less helpful signs of malignant melanoma?
- Asymmetry - Irregular colour - Elevation - Irregular border
285
What is the ABCDE for diagnosis of melanoma?
- Asymmetry - Border (irregular) - Colour (non-uniform) - Diameter (>7mm) - Elevation
286
What is the treatment for malignant melanoma?
- Urgent excision can be curative | - Chemotherapy gives response in 10-30%
287
How does squamous cell cancer usually present?
Ulcerated lesion with hard, raised edges in sun-exposed sites
288
Give three sites where squamous cell cancer may begin.
- In solar keratoses - On lips of smokers - In long-standing ulcers
289
What are solar keratoses?
Rough patches of skin from long-term sun exposure. | They have crumbly, yellow-white crusts.
290
Describe local destruction and metastases in squamous cell cancer.
- Local destruction may be extensive | - Metastases to lymph nodes are rare
291
What is the treatment for squamous cell cancer?
Excision and radiotherapy
292
What is another name for basal cell carcinoma?
Rodent ulcer
293
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.
294
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.
295
Describe the metastasis status in basal cell carcinoma.
Metastases are very rare.
296
What are the complications if a basal cell carcinoma is left untreated?
Slowly causes local destruction.
297
What is the treatment for basal cell carcinomas?
- Excision - Cryotherapy - Topical flurouracil or imiquimod for superficial carcinomas
298
Name two premalignant skin lesions.
- Solar keratoses | - Bowen’s disease
299
How does the skin appear in Bowen’s disease?
Slow-growing red/brown scaly plaque.
300
What can Bowen’s disease progress to?
Squamous cell carcinoma.
301
What is an ulcer?
An abnormal break in an epithelial or mucosal surface.
302
What factors should be examined when examining an ulcer?
- Site - Number - Surface area - Depth - Edge - Base - Discharge - Lymphadenopathy - Sensation - Healing - Temperature - Shape
303
What tests should be performed for a skin ulcer?
Skin and ulcer biopsy.
304
What is the management for skin ulcers?
Treat causes and focus on prevention.
305
How do venous ulcers develop?
Persistent high pressures in the veins damage the skin. | Can be due to venous insufficiency
306
How do arterial ulcers develop?
Reduction in arterial blood flow leads to decreased perfusion and poor healing.
307
How does a neuropathic ulcer occur?
Loss of protective sensation as a result of peripheral neuropathy.
308
How does an infective ulcer occur?
As the result of an infection.
309
How do traumatic ulcers occur?
Repetitive damage as a result of trauma.
310
How do vasculitic ulcers occur?
Due to inflammation of the blood vessels.
311
What is cellulitis?
Acute, painful, and potentially serious infection of the dermis and subcutaneous tissues.
312
Which types of bacteria most commonly cause cellulitis?
Streptococcus or Staphylococcus
313
Describe the borders in cellulitis.
Poorly demarcated.
314
What is erysipelas?
A superficial form of cellulitis.
315
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
316
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
317
What do red streaks away from the cellulitic area in cellulitis indicate?
Progression into the lymphatic system.
318
What is the management of cellulitis?
- Rest - Elevation - Analgesia - Flucloxacillin antibiotics (erythromycin if penicillin allergy) - Other antibiotics can be used
319
What is necrotising faciitis.
Rapidly progressive infection of the deep fascia causing necrosis of subcutaneous tissue.
320
How does necrotising faciitis usually present?
Intense pain over infected skin and underlying muscle. | Patients are systemically ill.
321
What is the major cause of necrotising faciitis?
Group A b-haemolytic streptococci (but infection is often polymicrobial)
322
What is the treatment for necrotising faciitis?
- Radical debridement (removal of damaged tissue) - Potentially amputation - IV antibiotics
323
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
324
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
325
Which is the most common type of malignant breast cancer?
Invasive ductal carcinoma
326
Which type of breast cancer tends to affect younger patients?
Medullary cancer
327
Which type of breast cancer tends to affect elderly patients?
Colloid/mucoid cancer
328
What does the triple assessment of breast lumps involve?
- Clinical examination - Histology/cytology - Mammography/ultrasound
329
What investigations should be carried out to stage breast cancer?
- CXR - Bone scan - Liver UUS/CT/MRI/PET-CT - LFTs - Calcium
330
Describe stage 1 breast cancer.
Confined to breast, mobile.
331
Describe stage 2 breast cancer.
Growth confined to breast, mobile, lymph nodes in ipsilateral axilla.
332
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
333
Describe stage 4 breast cancer.
- Complete fixation of tumour to chest wall | - Distant metastases
334
What factor gives a better prognosis in breast cancer?
Oestrogen receptor positive
335
Approximately what percentage of breast cancers are oestrogen receptor positive?
60-70%
336
Give a factor in breast cancer which is associated with aggressive disease and poor prognosis.
Over-expression of HER2 (growth factor receptor gene).
337
Approximately what percentage of breast cancers over express HER2?
30%
338
What are the four steps of the treatment of stage 1-2 breast cancer?
- Surgery - Radiotherapy - Chemotherapy - Endocrine agents
339
What is the aim of endocrine agents in treating breast cancer?
Decrease oestrogen activity
340
Give four endocrine agents/treatments that are used in oestrogen receptor positive breast cancers.
- Tamoxifen - Aromatase inhibitors - Ovarian ablation - GnRH analogues
341
Give two treatments used for bone metastases in breast cancer.
- Radiotherapy | - Bisphosphonates
342
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
343
What is amyloidosis?
A group of disorders characterised by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation.
344
Give three conditions that amyloidosis is a feature of.
- Alzheimer’s disease - Type 2 diabetes mellitus - Haemodialysis-related amyloidosis
345
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
346
Give three conditions that primary amyloidosis is associated with.
- Myeloma - Waldenstrom’s macroglobulinaemia - Lymphoma
347
Give five organs that can be affected by amyloidosis.
- Kidneys - Heart - Nerves - Gut - Vascular
348
Give three consequences of amyloidosis affecting the kidney.
- Glomerular lesions - Proteinuria - Nephrotic syndrome
349
Give three consequences of amyloidosis affecting the heart.
- Restrictive cardiomyopathy - Arrhythmias - Angina
350
Give two consequences of amyloidosis affecting the nerves.
- Peripheral and autonomic neuropathy | - Carpel tunnel syndrome
351
Give seven consequences of amyloidosis affecting the gut.
- Macroglossia - Malabsorption - Weight loss - Perforation - Haemorrhage - Obstruction - Hepatomegaly
352
Give a consequence of amyloidosis affecting the vascular system.
Purpura (especially periorbital)
353
Give two treatment options for primary amyloidosis.
- Oral melphalan + prednisolone (chemotherapy + steroid) | - Potentially blood stem cell transplant
354
Briefly describe the pathogenesis of secondary amyloidosis.
Amyloid derived from serum amyloid A (an acute phase protein).
355
When does secondary amyloidosis occur?
In chronic inflammation and infections.
356
Name three organs involved in secondary amyloidosis.
- Kidneys - Liver - Spleen
357
Describe the presentation of secondary amyloidosis.
- Proteinuria - Nephrotic syndrome - Hepatosplenomegaly - NOT macroglossia - Cardiac involvement rare
358
What is the treatment for secondary amyloidosis?
Treat underlying condition
359
Briefly describe the pathogenesis of familial amyloidosis.
Autosomal dominant mutation in transthyretin transport protein produced by the liver.
360
Describe the presentation of familial amyloidosis.
Sensory or autonomic neuropathy with/without cardiac and renal involvement.
361
What can be done to potentially cure familial amyloidosis?
Liver transplant
362
How is amyloidosis diagnosed?
Biopsy of affected tissue
363
What is the median survival time in amyloidosis?
1-2yrs
364
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.
365
Briefly describe the pathophysiology of primary lymphoedema.
Faulty lymphatic drainage due to mutations in genes responsible for the development of the lymphatic system.
366
What is secondary lymphoedema?
When the lymphatic system has previously been working but becomes damaged.
367
Give nine causes of secondary lymphoedema.
- Cancer surgery - Radiotherapy - Infections (cellulitis) - Filariasis - Inflammation - Venous diseases - Obesity - Trauma/injury - Immobility
368
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
369
How is diagnosis of lymphoedema usually made?
History and clinical examination
370
Give the four components of decongestive lymphatic therapy for lymphoedema.
- Compression bandages - Skin care - Exercises - Specialised massage techniques
371
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)
372
Define sarcoma.
A malignant tumour of connective tissue.
373
What are the two general types of sarcoma? | Which is more common?
- Bone sarcoma | - Soft tissue sarcoma (more common)
374
Give three types of soft tissue sarcoma.
- Gastrointestinal stromal tumours (GIST) - Gynaecological sarcomas - Retroperitoneal sarcomas
375
Give four diagnostic methods for sarcomas.
- Clinical examination - X-ray/CT/endoscopic ultrasound/PET/MRI - Biopsy - Bone scan
376
What are the three treatment options for sarcomas? | Which is the first treatment?
- Surgery (first treatment) - Radiotherapy - Chemotherapy
377
When is chemotherapy usually used to treat sarcomas?
Used to treat bone sarcomas before or after surgery.
378
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%
379
Describe a stage 1 sarcoma.
- Low grade - Small (<5cm) - Not spread
380
Describe stage 2 sarcoma.
- Cancer of any grade (usually larger than grade one) | - Not spread to other parts of the body
381
Describe stage 3 sarcoma.
- High grade | - Not spread
382
Describe stage 4 sarcoma.
- Any grade or size | - Spread to other parts of the body
383
Give three ‘positive’ risk factors for IHD.
- Fruit/veg - Exercise - Moderate alcohol
384
What is angina pectoris?
A symptom which occurs as a consequence of restricted coronary blood flow.
385
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.
386
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)
387
What causes Prinzmetal’s angina?
Coronary spasm
388
What causes microvascular angina?
Syndrome X
389
What issues with supply can precipitate angina?
- Anaemia - Hypoxaemia - Polycythemia - Hypothermia - Hypovolaemia - Hypervolaemia
390
What issues with demand can precipitate angina?
- Hypertension - Tachyarrhythmia - Valvular heart disease - Hyperthyroidism - Hypertrophic cardiomyopathy - Cold weather - Heavy metals - Emotional stress
391
Describe the three characteristics of anginal chest pain.
- Heavy, central, tight, radiation to arms/jaw/neck - Precipitated by exertion - Relieved by rest/GTN
392
Give nine differential diagnoses of angina.
- Pericarditis - Myocarditis - Pulmonary embolism - Pleurisy - Chest infection - Dissection of aorta - Gastro-oesophageal (reflux, spasm, ulceration) - Musculo-skeletal - Psychological
393
Describe the investigations often used for angina pectoris.
- Examination normal - ECG normal - Echo normal - Anatomical tests - Physiological tests
394
Give two anatomical tests that can be used to diagnose angina.
- CT angiography | - Invasive angiography
395
Give four physiological tests that can be used to diagnose angina.
- Exercise stress treadmill - Stress echo - Nuclear perfusion (SPECT) - Stress MRI
396
Give five methods of primary prevention of angina.
- Antihypertensives - Statins - Diabetic therapy - Smoking cessation - General dietary/exercise advice
397
Give five categories of medication that can be used to treat angina.
- betablockers - Nitrates - Calcium channel antagonists - Antiplatelets - Statins
398
What are two revascularisation techniques that can be used in IHD?
- Percutaneous coronary intervention (PCI) | - Coronary artery bypass graft (CABG)
399
Name three acute coronary syndromes.
- Unstable angina - Non ST elevation myocardial infarction (NSTEMI) - ST elevation myocardial infarction (STEMI)
400
What three characteristics can appear in unstable angina?
- Cardiac chest pain at rest - Cardiac chest pain with crescendo pattern - New onset angina
401
How is unstable angina diagnosed?
- History - ECG - No significant rise in troponin
402
When is the diagnosis of an NSTEMI made?
Usually retrospectively after troponin results and other investigations.
403
What long term ECG changes occur after a STEMI?
Pathological Q waves
404
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
405
Give three groups of patients in which cardiac chest pain associated with an acute MI may be atypical.
- Elderly - Women - Diabetics
406
What is Levine’s sign?
Patient puts fist to their chest (indicates cardiac chest pain)
407
What are the four major management points for an acute MI?
- Morphine - Oxygen - Nitrates - Aspirin
408
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.
409
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
410
What is the pathophysiological difference between a STEMI and an NSTEMI?
``` STEMI = complete occlusion of artery NSTEMI = severe narrowing of artery ```
411
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.
412
What are eight risk factors for DVT?
- Age - Surgery/immobility/leg fracture - Cancer - Obesity - Oestrogen (OC, HRT) - Pregnancy - Long haul flights - Inherited thrombophilia
413
Why is a clinical diagnosis of DVT unreliable?
Symptoms and signs are non-specific.
414
What are the symptoms of DVT?
Pain and swelling (usually in calf)
415
What are the signs of DVT?
- Tenderness - Swelling - Warmth - Discolouration - Mild fever - Pitting oedema
416
How can D-dimer be used in the diagnosis of DVT?
Normal excludes diagnosis but positive is not specific for disease.
417
Give six conditions which will result in an increased D dimer.
- Surgery - Pregnancy - Infection - Inflammation - Malignancy - DVT
418
How can a DVT be diagnosed?
Ultrasound compression test on proximal veins.
419
What is the treatment for DVT?
- Low molecular weight heparin - Oral warfarin or DOAC - Compression stockings - Treat underlying cause
420
Give four methods of mechanical prevention of DVT.
- Hydration - Early mobilisation - Compression stockings - Foot pumps
421
Give a chemical method of prevention for DVT.
Low molecular weight heparin.
422
What are the signs of a pulmonary embolism?
- Hypotension - Cyanosis - Tachycardia - Tachypnoea - Pleural rub - Severe dyspnoea - Right heart strain/failure - Signs/symptoms of DVT
423
What are the symptoms of pulmonary embolism?
- Breathlessness | - Pleuritic chest pain
424
Give six differential diagnoses of pulmonary embolism.
- Musculoskeletal - Infection - Malignancy - Pneumothorax - Cardiac causes - GI causes
425
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
426
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
427
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.
428
What is the definition of heart failure?
Cardiac output is inadequate for the body’s requirements.
429
What causes congestion in heart failure?
RAAS and sympathetic nervous system activated due to decreased cardiac output.
430
What is systolic heart failure?
Inability of the ventricle to contract normally, resulting in decreased cardiac output.
431
What is the typical ejection fraction in systolic heart failure?
<40%
432
What is another name for systolic heart failure?
Heart failure with reduced ejection fraction.
433
Give three causes of systolic heart failure.
- IHD - Myocardial infarction - Cardiomyopathy
434
What is diastolic heart failure?
- Inability of the ventricle to relax and fill normally.
435
Describe the ejection fraction in diastolic heart failure.
>50%
436
Give four causes of diastolic heart failure.
- Constrictive pericarditis - Cardiac tamponade - Restrictive cardiomyopathy - Hypertension
437
Give another name for diastolic heart failure.
Heart failure with preserved ejection fraction.
438
Give three causes of right ventricular failure.
- Left ventricular failure - Pulmonary stenosis - Lung disease
439
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
440
What are the symptoms of right ventricular failure?
- Peripheral oedema - Ascites - Nausea - Anorexia - Facial engorgement - Pulsation in face and neck - Epistaxis (nose bleed)
441
Describe acute heart failure.
New onset or decompensation of chronic heart failure.
442
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
443
What is high-output cardiac failure?
Output normal or increased but fails to meet hugely increased needs.
444
What are some causes of high-output heart failure?
- Anaemia - Pregnancy - Hyperthyroidism - Paget’s disease - Arteriovenous malformation - Beriberi
445
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
446
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
447
How many of each criteria are needed for a diagnosis of heart failure?
2 Major Or 2 minor + 1 major
448
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
449
What investigations can rule out heart failure?
- ECG and B-type natriuretic peptide normal
450
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
451
What is the 5 year mortality in heart failure?
75%
452
Give five methods of pathophysiology of heart failure.
- Ischaemia - Valvular - Myopathic - Hypertensive - Cor Pulmonale
453
What is Cor Pulmonale?
Pulmonary hypertension of the lungs which causes right-sided heart failure.
454
According to NYHA (New York Heart Association), what is Class I heart failure?
No limitation (asymptomatic)
455
According to NYHA (New York Heart Association), what is Class II heart failure?
Slight limitation (mild HF)
456
According to NYHA (New York Heart Association), what is Class III heart failure?
Marked limitation (symptomatically moderate HF)
457
According to NYHA (New York Heart Association), what is Class IV heart failure?
Inability to carry out physical activity without discomfort (symptomatically severe HF)
458
What is primary hypertension and what percentage of cases does it account for?
Hypertension with no obvious cause. | Accounts for 95%.
459
What is secondary hypertension and what percentage of cases does it account for?
Hypertension with a known cause. | Accounts for 5% of cases.
460
What is the cut off measurement for hypertension in the clinic?
140/90mmHg
461
What is the cut off for hypertension at home?
135/85mmHg
462
What is stage 1 hypertension and how is it treated?
140/90mmHg - 160/100mmHg | Treated with lifestyle changes
463
What is stage 2 hypertension and how is it treated?
Above 160/100mmHg. | Treated with medications.
464
What is malignant hypertension?
Rapid rise in blood pressure leading to vascular damage.
465
What is a sign of malignant hypertension?
Bilateral retinal haemorrhages and exudates.
466
What are the symptoms of malignant hypertension?
- Headache | - Visual disturbances
467
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)
468
What are the symptoms of hypertension.
Usually asymptomatic
469
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
470
What would you expect the drop in blood pressure to be on tablets?
10mmHg
471
What blood pressure should be aimed for when treating hypertension?
140/90mmHg | Lower for diabetics for people with proteinuria.
472
What are the three major lifestyle changes that can reduce blood pressure?
- Weight loss - Drink less alcohol - Reduce salt intake
473
Give five complications of hypertension.
- Stroke - IHD - Renal failure - Heart failure - Losing 5 years of life
474
What is an aneurysm?
A dilation >50% of a blood vessels original diameter.
475
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.
476
Describe the pathophysiology of an aortic aneurysm.
Degeneration of elastic lamellae and smooth muscle loss.
477
Give five causes of an aortic aneurysm.
- Atheroma - Trauma - Infection - Connective tissue disorders - Inflammatory
478
Give five complications of an aortic aneurysm.
- Rupture - Thrombosis - Embolism - Fistulae - Pressure on other structures
479
Are AAA more common in men or women?
Men
480
Describe current screening for AAA.
All men screened at age 65.
481
What are the symptoms of an unruptured AAA?
Often no symptoms, but may cause abdominal or back pain.
482
Give four risk factors for rupture of an AAA.
- High blood pressure - Smoker - Female - Strong family history
483
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
484
Describe the management of a ruptured AAA.
- ECG - Take blood and cross-match - Catheterise - IV access - Treat shock - Take patient straight to theatre
485
What is an aortic dissection?
Blood splits the aortic media. | As the dissection expands, branches of the aorta occlude sequentially.
486
What are the signs/symptoms of an aortic dissection?
Sudden tearing chest pain with or without radiation to the back.
487
What is a type A aortic dissection?
Dissection involving ascending aorta.
488
What is a type B aortic dissection?
Dissection not involving ascending aorta.
489
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
490
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
491
What is claudication?
A condition in which cramping pain in the leg is induced by exercise.
492
Briefly describe the pathogenesis of peripheral vascular disease.
Atherosclerosis causing stenosis of the arteries.
493
What are the symptoms of peripheral vascular disease?
- Cramping in calf, thigh, or buttock after walking for a given distance - Cramping relieved by rest
494
What is the distance called that a person with peripheral vascular disease can walk before symptoms appear?
Claudication distance
495
If the patient suffers cramping in the calf, where is the peripheral vascular disease likely to be?
Femoral
496
If a patient suffers cramping in the buttock, where is the peripheral vascular disease likely to be?
Iliac
497
Give three symptoms of peripheral vascular disease which indicate critical ischaemia.
- Ulceration - Gangrene - Foot pain at rest
498
What are signs of peripheral vascular disease?
- Absent femoral, popliteal, foot pulses - Cold, white legs - Atrophic skin - Punched out ulcers - Postural dependent colour change - Increased capillary filling time
499
What conditions is it important to exclude in peripheral vascular disease?
- Diabetes mellitus | - Arteritis
500
What imaging can be carried out in peripheral vascular disease?
Colour duplex ultrasound scan
501
How is peripheral vascular disease managed?
- Risk factor modification - Antiplatelet agent (Clopidogrel) - Supervised exercise programmes - Vasoactive drugs - Percutaneous transluminal angioplasty - Surgical reconstruction - Amputation
502
What can cause critical ischaemia?
- Thrombosis in situ - Emboli - Graft/angioplasty occlusion - Trauma
503
Give 6 signs/symptoms of acute ischaemia.
- Pale - Pulseless - Painful - Paralysed - Paraesthetic - Perishingly cold
504
What is the management for critical ischaemia?
- Revascularisation surgery within 4-6 hours to save limb - Tissue plasminogen activator and anticoagulate with heparin after surgery if cause was embolic - Amputation
505
What is acute pericarditis?
Inflammatory pericardial syndrome with or without effusion.
506
What is the main cause of acute pericarditis?
Viral
507
Give six less common causes of acute pericarditis.
- Bacteria (TB) - Autoimmune - Neoplastic - Metabolic - Myocardial infarction - Iatrogenic
508
Give four autoimmune conditions which can cause acute pericarditis.
- Sjogren syndrome - Rheumatoid arthritis - Scleroderma - Systemic vasculitides
509
Give two metabolic causes of acute pericarditis.
- Uraemia | - Myxoedema
510
What is the name of pericarditis which occurs after a myocardial infarction?
Dressler’s Syndrome
511
Give four ‘miscellaneous’ causes of acute pericarditis.
- Amyloidosis - Aortic dissection - Pulmonary arterial hypertension - Chronic heart failure
512
What are the clinical features of acute pericarditis?
- Sharp, central chest pain (worse on lying flat, may have relief from sitting forward) - Rapid onset - Left anterior chest or epigastrum pain - Pain may radiate to left arm or trapezius ridge - Evidence of pericardial effusion or cardiac tamponade - Pericardial rub - Sinus tachycardia - Fever
513
What are some less common symptoms of pericarditis?
- Dyspnoea - Cough - Hiccups - Signs of viral infection - History of other causes
514
How is diagnosis of pericarditis made?
2 out of 3 from: - Chest pain - Friction rub - ECG changes
515
What tests are carried out to diagnose acute pericarditis?
- ECG - Bloods (modest increase in WBC and troponin release) - CXR - Echocardiogram
516
Describe the ECG changes associated with acute pericarditis.
- Diffuse ST elevation - Concave ST segment - PR depression
517
What is the most common differential diagnosis for acute pericarditis?
Myocardial infarction
518
What is the treatment for acute pericarditis?
- Sedentary activity - NSAID/aspirin - Colchicine
519
What is constrictive pericarditis?
Where the heart becomes encased in a rigid pericardium.
520
When does constrictive pericarditis commonly occur?
After bacterial (TB) pericarditis.
521
What is the main clinical feature of constrictive pericarditis?
Right heart failure
522
What does the CXR usually show in constrictive pericarditis?
Small heart with/without pericardial calcification.
523
What is the management of constrictive pericarditis?
Surgical excision
524
What is a pericardial effusion?
Excess fluid in the pericardial space.
525
What is cardiac tamponade?
Clinical syndrome resulting from pericardial effusion.
526
How does chronic pericardial effusion develop?
Chronic accumulation of fluid allows adaptation of the parietal pericardium. Compliance of the pericardium reduces the effect on diastolic filling of the chambers. Therefore very slowly accumulating effusions rarely cause tamponade.
527
Describe and explain the physiological change in blood pressure on inspiration.
- Thoracic pressure decreases - More blood pulled into right ventricle - Less room for left ventricle to fill - Slight decrease (<10mmHg) in blood pressure on inspiration
528
Name three signs of pericardial effusion.
- Kussmauls sign - Pulsus Paradoxus - Beck’s triad
529
What is Kussmauls sign?
- Right ventricle compliance reduced (less room to expand on inspiration) - Right ventricle pressure increases - Blood forced back into jugular vein on inspiration
530
Describe pulsus paradoxus.
- Right ventricle increases in volume as more blood pulled in on inspiration - Even less filling of left ventricle than usual, leading to bigger decrease in blood pressure
531
What are the three elements of Beck’s Triad?
- Hypotension - Elevated JVP - Quiet heart sounds
532
What is the treatment for hypocalcaemia?
- Adcal | - Calcium gluconate
533
What is the treatment for hypercalcaemia?
- IV saline (for dehydration) | - Bisphosphonates
534
What does a high alkaline phosphatase indicate in hypercalcaemia?
Hypercalcaemia is due to increased bone turnover.
535
What is the normal area of the aortic valve, and at what area do symptoms appear in aortic stenosis?
Normal area is 3-4cm2 | Symptoms start at 1cm2
536
Describe the pathophysiology of aortic stenosis.
- Pressure gradient develops between left ventricle and aorta - Left ventricle undergoes compensatory hypertrophy - When compensatory mechanisms exhausted, LV function declines
537
Give four causes of aortic stenosis.
- Degenerative calcification - Congenital bicuspid valve - Congenital aortic stenosis - Rheumatic heart disease
538
Describe the presentation of aortic stenosis.
- Angina - Exertional syncope - Dyspnoea on exertion - Sudden death
539
What are the signs of aortic stenosis?
- Slow rising pulse - Decreased pulse amplitude - Soft/absent second heart sound - S4 gallop - Ejection systolic murmur (crescendo-decrescendo character)
540
What does the loudness of the murmur in aortic stenosis say about the severity?
Nothing
541
What test is used to assess aortic stenosis?
Echocardiography (look for LV size and function, and doppler derived gradient and valve area)
542
What is the differential diagnosis of aortic stenosis?
Hypertrophic cardiomyopathy
543
What is the management for aortic stenosis?
- Dental hygiene to avoid IE - Surgical replacement - Transcatheter aortic valve implantation (TAVI)
544
What are the indications for surgery in aortic stenosis?
- Any symptomatic patient - Decreasing ejection fraction - Undergoing CABG
545
What is mitral regurgitation?
Backflow of blood from the left ventricle to the left atrium during systole.
546
Describe the pathophysiology of mitral regurgitation.
- Volume overload from the left ventricle - Compensatory mechanisms include LA enlargement, LV hypertrophy, increased contractility - LA dilation leads to RV dysfunction due to pulmonary hypertension - LV volume overload leads to dilatation and progressive heart failure
547
Give four causes of mitral regurgitation.
- Myxomatous degeneration (floppy valve) - Ischaemic mitral regurgitation - Rheumatic heart disease - Infective endocarditis
548
What are the symptoms of mitral regurgitation?
- Exertional dyspnoea - Fatigue - Palpitations
549
What are the signs of mitral regurgitation?
- Atrial fibrillation - Displaced hyperdynamic apex beat - Soft S1 - S3 (LA overload) - Loud P2 (pulmonary hypertension) - Pansystolic murmur at apex radiating to axilla
550
What does the intensity of the murmur in mitral regurgitation tell you about the severity?
Intensity correlates with intensity.
551
What do ECG findings correlate to in mitral regurgitation? | What do the ECG changes say about the structure of the heart?
- Left atrial enlargement - Atrial fibrillation - Left ventricular hypertrophy
552
What does the CXR show in mitral regurgitation?
- Big LA and LV | - Central pulmonary artery enlargement
553
What other tests are carried out in mitral regurgitation and why?
- Echocardiogram (assess LV function and aetiology) | - Doppler echo (assess size of regurgitation)
554
What is the management of mitral regurgitation?
- Control rate if atrial fibrillation (b-blockers, CCB, digoxin) - Vasodilator (ACEi, hydralazine) - Anticoagulate - Diuretics for fluid overload - Echocardiography to monitor
555
What are the indications for surgery in mitral regurgitation?
- Symptoms - Ejection fraction <60% - Left ventricular end systolic diameter >45mm - New onset atrial fibrillation
556
Define aortic regurgitation.
Leakage of blood into the left ventricle during diastole due to ineffective coaptation of the aortic cusps.
557
Describe the pathophysiology of aortic regurgitation.
- Combined pressure and volume overload - Compensatory mechanisms include LV dilation and LV hypertrophy - Progressive dilatation leads to heart failure
558
Give three causes of aortic regurgitation.
- Bicuspid aortic valve - Rheumatic heart disease - Infective endocarditis
559
What are the symptoms of aortic regurgitation?
- Asymptomatic until 4th or 5th decade - Exertional dyspnoea - Orthopnoea - Paroxysmal nocturnal dyspnoea - Palpitations
560
What are the signs of aortic regurgitation?
- Wide pulse pressure - Hyperdynamic and displaced apex - Diastolic blowing murmur (decrescendo character at left sternal border) - Austin Flint murmur (at apex) - Systolic ejection murmur
561
Describe Austin Flint murmur.
Regurgitant jet impinges on anterior mitral valve causing it to vibrate.
562
What does the CXR show in aortic regurgitation?
- Cardiomegaly - Dilated ascending aorta - Pulmonary oedema
563
What is assessed on echocardiography in aortic regurgitation?
- Aortic valve and aortic root | - LV dimensions and function
564
What is the main goal of treatment in aortic regurgitation?
Reduce systolic hypertension
565
Describe the treatment for aortic regurgitation.
- Vasodilators - ACEi - Echo to monitor - Valve replacement
566
What are the indications for valve replacement in aortic regurgitation?
- Symptoms - EF<50% - Dilated LV
567
Define mitral stenosis.
Obstruction of left ventricle inflow that prevents proper filling during diastole.
568
What is the normal area of the mitral valve, and at what area do symptoms begin to occur?
Normal area is 4-6cm2. | Symptoms appear at 2cm2.
569
Give three causes of mitral stenosis. | Which is the most common?
- Rheumatic heart disease (MOST COMMON) - Infective endocarditis - Mitral annular calcification
570
Describe the pathophysiology of the symptoms of mitral stenosis.
- Dyspnoea (LA dilation leads to pulmonary congestion) - Left atrial enlargement and fibrillation due to increased transmitral pressures - Right heart failure symptoms due to pulmonary hypertension - Hemoptysis (coughing up blood) due to rupture of bronchial vessels
571
What are the signs of mitral stenosis?
- Prominent a wave in jugular venous pulsations - Signs of right sided heart failure - Mitral facies - Low pitched diastolic rumble (most prominent at apex) - Loud opening S1 snap
572
What does the intensity of the murmur in mitral stenosis tell you about severity?
Nothing
573
Briefly describe the pathophysiology of mitral facies.
Vasodilation due to decreased cardiac output, resulting in pinkish-purple patches on the cheeks.
574
What will be indicated on the ECG in mitral stenosis?
- Atrial fibrillation | - Left atrial enlargement
575
What will be seen on the CXR in mitral stenosis?
- LA enlargement - Pulmonary oedema - Mitral valve calcification
576
What is assessed on the echocardiogram in mitral stenosis?
- Mitral valve mobility - Gradient - Mitral valve area
577
What is the management in mitral stenosis?
- Echocardiography to monitor - Control fibrillation (b-blockers, CCBs, digoxin) - Diuretics for fluid overload - Anticoagulate if increased thromboembolism risk - Percutaneous mitral balloon valvotomy (if symptomatic)
578
Which valvular dysfunction occurs physiologically in 80% of normal people?
Mitral regurgitation
579
In aortic and mitral stenosis, what area is considered to be severe stenosis?
<1cm2
580
Define shock.
Circulatory failure resulting in inadequate organ perfusion. Low blood pressure <90mmHg with evidence of tissue hypoperfusion.
581
What systolic BP and mean arterial pressures are the upper cut offs for shock?
BP<90mmHg | MAP<65mmHg
582
Give three signs of tissue hypoperfusion.
- Mottled skin - Low urine output - Serum lactate >2mmol/L
583
Give the signs of shock.
- Low GCS/agitation - Pallor - Cool peripheries - Tachycardia - Slow capillary refills - Tachypnoea - Oligouria
584
What are the causes of hypovolaemic shock?
- Trauma - Ruptured aortic aneurysm - GI bleed - Vomiting - Burns - ‘Third space’ losses (too much fluid moves from blood to interstitial space)
585
What are the causes of pump failure shock?
- Cardiogenic shock - Pulmonary embolism - Tension pneumothorax - Cardiac tamponade
586
What are the causes of neurogenic shock?
- Spinal cord injury - Epidural - Spinal anaesthesia - Disruption to autonomic nervous system
587
What are the endocrine causes of shock?
- Addison’s disease | - Hypothyroidism
588
How is shock assessed?
- Check ECG | - Look for signs of type of shock
589
If someone in shock is cold and clammy, what is the likely cause?
Cardiogenic shock or fluid loss.
590
If someone in shock is warm and well perfused with bounding pulse points what is the likely cause?
Septic shock
591
What is the management for hypovolaemic shock?
- Identify and treat underlying cause - Raise legs - Fluid bolus
592
What is the management for haemorrhagic shock?
- Stop bleeding if possible - Fluid bolus - Crossmatch blood
593
What is the management for neurogenic shock?
- Fluids | - Vasoconstrictors
594
What are the causes of cardiogenic shock?
- Myocardial infarction - Arrhythmias - Pulmonary embolus - Tension pneumothorax - Cardiac tamponade - Myocarditis - Valve destruction - Aortic dissection
595
What is the management of cardiogenic shock?
- Treat underlying cause - Oxygen - Diamorphine - Investigations and monitoring
596
What is meant by cardiomyopathy?
Disease of the heart muscle. It is often genetic.
597
Describe dilated cardiomyopathy.
Dilated, flabby heart often caused by cytoskeletal gene mutations.
598
Which chamber/s are most commonly affected in dilated cardiomyopathy?
Commonly all four chambers are dilated.
599
Describe the thickness of the heart muscle in dilated cardiomyopathy.
Thin
600
Describe the presentation of dilated cardiomyopathy.
- Heart failure symptoms | - Arrhythmias can occur late on
601
What does the CXR show in dilated cardiomyopathy?
- Cardiomegaly | - Pulmonary oedema
602
What does the ECG show in dilated cardiomyopathy?
- Tachycardia - T wave changes - Poor R wave progression
603
What is the treatment for dilated cardiomyopathy?
- Bed rest - Diuretics - Digoxin - ACEi - Anticoagulants - Biventricular pacing - Cardiac defibrillator - Cardiac transplantation
604
What are the causes of restrictive cardiomyopathy?
- Idiopathic - Amyloidosis - Haemochromatosis - Sarcoidosis - Scleroderma - Loffler’s eosinophilic endocarditis - Endomyocardial fibrosis
605
Describe the presentation of restrictive cardiomyopathy.
- Like constrictive pericarditis - Features of right ventricular failure predominate - Increased jugular venous pressure - Hepatomegaly - Oedema - Ascites
606
How is restrictive cardiomyopathy diagnosed?
Cardiac catheterisation
607
How is restrictive cardiomyopathy treated?
Treat the cause
608
What gene mutations cause hypertrophic cardiomyopathy?
Sarcomeric protein gene mutation
609
Describe the pathophysiology of hypertrophic cardiomyopathy.
- Left ventricle outflow tract obstruction from asymmetric septal hypertrophy - Thickening around left ventricle causes small ventricle and high ejection fraction - Diastolic dysfunction - Myocyte disarray leading to arrhythmias - Coronary arteries become hypertrophied leading to ischaemia
610
What is the leading cause of sudden cardiac death in the young?
Hypertrophic cardiomyopathy
611
What are the signs/symptoms of hypertrophic cardiomyopathy?
- Sudden death - Angina - Dyspnoea - Palpitation - Dizzy spells - Syncope
612
What does the ECG show in hypertrophic cardiomyopathy?
Large voltages and T wave inversion
613
What is the treatment for hypertrophic cardiomyopathy?
- B blocker or verapamil for symptoms - Amiodarone for arrhythmias - Anticoagulants - Consider implantable defibrillator
614
What gene mutations cause arrhythmogenic cardiomyopathy?
Desmosome gene mutations
615
Describe the histological appearance of the heart in arrhythmogenic cardiomyopathy.
Ventricular muscle replaced with fat and fibrous tissue
616
Which chamber/s of the heart does arrhythmogenic cardiomyopathy usually affect?
Right ventricle then left
617
What ECG changes occur in arrhythmogenic cardiomyopathy?
- T wave inversion | - Epsilon wave in V1-V3
618
In what percentage of patients with congenital heart defects are intellectual disabilities also found?
10%
619
How and when are congenital heart defects usually first picked up?
Foetal echocardiography at 18-22 weeks.
620
Give four heart defects that give a 50% chance of maternal mortality if the patient were to become pregnant.
- Pulmonary hypertension - Severe left heart obstruction - Systemic ventricular impairment (EF<30%) - Marfans syndrome with aortic root diameter >47mm
621
What are the four components of Tetralogy of Fallot?
1. Ventricular septal defect 2. Pulmonary stenosis 3. Hypertrophy of right ventricle 4. Overriding aorta
622
Describe the pathophysiology of Tetralogy of Fallot.
Overriding aorta prevents proper development of pulmonary arteries. Stenosis of RV outflow leads to high pressure in RV. Deoxygenated blood passes from RV to LV.
623
Are patients blue (cyanotic) in Tetralogy of Fallot?
Yes
624
What percentage of congenital heart defects does Tetralogy of Fallot account for?
10%
625
What genetic abnormality is associated with Tetralogy of Fallot in 15% of patients?
22q11 deletion (DiGeorge syndrome)
626
Describe the treatment for Tetralogy of Fallot.
Close ventricular septal defect and reopen pulmonary artery by 2 years. Often get pulmonary valve regurgitation in adult life and require more surgery.
627
What is a ventricular septal defect?
Abnormal connection between the two ventricles.
628
What percentage of congenital heart defects do ventricular septal defects account for?
20%
629
Describe the pathophysiology of ventricular septal defects.
Blood flows from high pressure LV to RV. | Increased blood flow through lungs.
630
Are patients with ventricular septal defects usually cyanotic (blue)?
No
631
What are the clinical signs of a large ventricular septal defect?
- Breathless - Poor feeding - Failure to thrive - May lead to Eisenmengers syndrome - Small, breathless, skinny baby - Increased respiratory rate - Tachycardia - Big heart on CXR - Murmur varies in intensity
632
Describe the clinical presentation of a small ventricular septal defect.
- Asymptomatic - 1% endocarditis risk - Loud systolic murmur - Thrill (buzzing sensation) - Well grown - Normal heart rate/size
633
Describe the treatment for large and small ventricular septal defects.
LARGE - requires fixing in infancy | SMALL - need no intervention
634
Describe the pathophysiology of Eisenmengers syndrome.
- High pressure pulmonary blood flow - Damage to delicate pulmonary vasculature - Resistance to pulmonary blood flow increases - Right ventricular pressure increases (RV hypertrophy) - Shunt reverses direction - Patient becomes blue
635
What is an atrial septal defect?
Abnormal connection between the two atria.
636
Where is the opening between the atria located in a primum atrial septal defect?
At the level of the tricuspid and mitral valves.
637
Where is the opening between the atria located in a secundum atrial septal defect?
High up in the atrial septum.
638
Describe a sinus venosus atrial septal defect.
The superior vena cava straddles the two atria.
639
Describe the pathophysiology of atrial septal defects.
- Shunt is from left to right | - Increased blood flow to right heart and lungs
640
Is the patient blue (cyanotic) in atrial septal defects?
No
641
Describe the clinical signs associated with a large atrial septal defect.
- Right heart dilation - Shortness of breath on exertion - Increased chest infections - Pulmonary flow murmur - Fixed split second heart sound (delayed closure of PV as more blood has to get out) - Big pulmonary arteries and heart on CXR
642
Describe the clinical signs associated with a small atrial septal defect.
- No right heart dilatation - No symptoms - Shunt may increase with age
643
Describe the management of a large and small atrial septal defect.
LARGE - should be closed if stretch on right heart (surgical or percutaneous) SMALL - Leave alone
644
Give two possible complications that may arise from an atrial septal defect.
- Atrial arrhythmias | - Pulmonary hypertrophy
645
Give a syndrome that often occurs with atrio-ventricular septal defects.
Down’s Syndrome
646
Describe an atrio-ventricular septal defect.
Hole in the very centre of the heart, involving atrial septum, ventricular septum, and mitral/tricuspid valves.
647
Describe the atrioventricular valves in atrio-ventricular septal defects.
One big malformed valve which leaks.
648
Describe the clinical presentation of a complete atrio-ventricular septal defect.
- Breathless as neonate - Poor weight gain - Poor feeding - Torrential pulmonary blood flow
649
Describe the clinical presentation of a partial atrio-ventricular septal defect.
- Can present late in adulthood | - Presents like a small VSD/ASD
650
Describe the management of complete and partial atrio-ventricular septal defects.
COMPLETE - needs repair in infancy (surgically challenging) | PARTIAL - May be left alone if there is no right heart dilatation
651
Describe the pathophysiology of a patent ductus arteriosus.
- Blood flows from aorta to pulmonary arteries - High pressure in the lungs and Eisenmengers syndrome - Only cyanotic in toes, fingers are normal (as deoxygenated blood enters aorta after subclavian arteries)
652
Describe the clinical signs of a large patent ductus arteriosus.
- Continuous machinery murmur - Big heart - Breathless - Poor feeding - Failure to thrive
653
Describe the clinical signs of a small patent ductus arteriosus.
- Usually asymptomatic - Murmur found incidentally - Endocarditis risk
654
In which group of babies is patent ductus arteriosus more common?
Premature babies
655
Describe the treatment for a large patent ductus arteriousus.
Needs to be closed surgically, which can be surgical or percutaneous.
656
Describe coarctation of the aorta.
Narrowing (stenosis) of the aorta at the site of insertion of the ductus arteriosus.
657
Describe the presentation of a mild coarctation of the aorta.
- Hypertension (due to renin release from the kidney) | - Incidental murmur
658
Describe the clinical signs of coarctation of the aorta.
- Right arm hypertension - Bruits (buzzes) over the scapulae and back from collateral vessels - Murmur
659
When should coarctation of the aorta be treated?
- Severe needs urgent repair | - Mild should be repaired to avoid long term issues
660
Give three long-term issues associated with coarctation of the aorta.
- Hypertension - Re-coarctation requiring repeat intervention - Aneurysm formation at site of repair
661
Describe the three treatment options for coarctation of the aorta.
- Subclavian flap repair using subclavian artery (results in small left arm) - End to end repair - Coarctation angioplasty (stent) in adults
662
Give four complications of a bicuspid aortic valve.
- Can be severely stenotic in infancy or childhood - Degenerate quicker than normal valves - Become regurgitant earlier than normal valves - Associated with coarctation and dilation of ascending aorta
663
What are the signs of a bicuspid aortic valve?
- Pop as valve opens | - Whooshing as blood goes forward or back
664
What is pulmonary stenosis?
Narrowing of the right ventricle outflow (can be valvar, subvalvar, or supravalvar).
665
What are the clinical signs of severe pulmonary stenosis?
- Right ventricular failure (neonate) - Collapse - Poor pulmonary blood flow - Right ventricular hypertrophy - Tricuspid regurgitation
666
Describe the clinical signs of moderate/mild pulmonary stenosis.
- Well tolerated for many years | - Right ventricular hypertrophy
667
Describe the four treatment options for pulmonary stenosis.
- Balloon valvuloplasty (in infancy) - Open valvotomy - Open trans-annular patch - Shunt
668
Define infective endocarditis.
Infection of the heart valves or other endocardial lined structures within the heart (septal defects, pacemaker leads, surgical patches).
669
Give two ‘complications’ of infective endocarditis.
- Showers bacteria around blood stream | - Eats holes in heart valves
670
Give five types of infective endocarditis.
- Left sided native - Left sided prosthetic - Right sided (rarely prosthetic) - Device related (with or without valve) - Early or late (associated with valves)
671
Give three risk factors for infective endocarditis.
- Abnormal valve (regurgitant/prosthetic) - Introduction of infectious material into bloodstream (surgery) - Has had IE previously
672
Give four groups of people more at risk of infective endocarditis.
- Elderly - Young IV drug abusers - Young with congenital heart disease - Prosthetic heart valves
673
Describe the clinical presentation of infective endocarditis.
- New regurgitant heart murmur - Embolic events of unknown origin - Sepsis of unknown origin - Signs of systemic infection (fever) - Valve dysfunction (heart failure, arrhythmia)
674
Give five peripheral manifestations of infective endocarditis.
- Petechiae - Splinter haemorrhages - Osler’s nodes - Janeway lesions - Roth spots on fundoscopy
675
Describe Osler’s nodes.
Small erythematous subcutaneous nodules on digits.
676
Describe Janeway lesions.
Erythematous lesions on fingers/palm/soles.
677
Give the two major criteria for diagnosis of infective endocarditis.
- Bug grown from blood cultures | - Evidence of IE on echo/new valve leak
678
Give the five minor criteria in diagnosis of infective endocarditis.
- Predisposing factors - Fever - Vascular phenomena (emboli) - Immune phenomena - Equivocal (ambiguous) blood cultures
679
Give the three ‘pathways’ to diagnosing infective endocarditis using the Modified Dukes Criteria.
- 2 major - 1 major + 3 minor - 5 minor
680
What investigations can be performed to investigate infective endocarditis?
- Transthoracic echo - Transoesophageal echo - ECG
681
Describe the treatment for infective endocarditis.
- IV antibiotics for around 6 weeks - Treat complications - Surgery (when antibiotics fail, complications, remove infected devices, replace valve, remove large vegetations before embolism)
682
Define myeloma.
Neoplastic proliferation of bone marrow plasma cells.
683
What is the peak age for myeloma to develop?
70 years
684
Describe the pathophysiology of myeloma.
Abnormal proliferation of a single clone of plasma cell leading to secretion of immunoglobulin or immunoglobulin fragments. This causes dysfunction of many organs, and levels of other immunoglobulins to be very low.
685
Which immunoglobulins are secreted in myeloma?
IgG in 2/3 | IgA in 1/3
686
What are Bence Jones proteins?
Kappa or Lambda light chains present in the urine in myeloma.
687
What are the four consequences (end organ damage) of myeloma?
- Hypercalcaemia - Renal impairment - Anaemia, neutropenia, thrombocytopenia - Osteolytic bone lesions
688
Why do osteolytic bone lesions And hypercalcaemia occur in myeloma?
Increased osteoclast activation from signalling from myeloma cells.
689
Give three signs/symptoms of osteolytic bone lesions in myeloma.
- Backache - Pathological fractures - Vertebral collapse
690
Why do anaemia, neutropenia, and thrombocytopenia occur in myeloma?
Marrow infiltration by plasma cells.
691
What is immunoparesis in myeloma?
The lack of antibodies, other than those secreted by abnormal plasma cells.
692
Give four symptoms of myeloma caused by marrow infiltration.
- Symptoms of anaemia - Infections - Bleeding - Recurrent bacterial infections
693
Why does renal impairment occur in myeloma?
Due to light chain deposition
694
Give three mechanisms of renal impairment in myeloma.
- Precipitation of light chains with Tamm-Horsfall protein - Monoclonal antibodies induce glomerular changes - Light chains cause amyloidosis in the kidney
695
What is Tamm-Horsfall protein?
Protein secreted in the urine of healthy individuals.
696
What does the full blood count show in myeloma?
Anaemia
697
What does the blood film show in myeloma?
``` Rouleaux formation (red blood cells sticking together). This is not specific. ```
698
What do the plasma viscosity and ESR show in myeloma.
Both raised
699
What does the urea and creatinine show in myeloma?
Raised
700
What will the calcium measurement be in myeloma?
High
701
What will the X rays show in myeloma?
Lytic ‘punched-out’ lesions
702
How can the cells of the bone marrow be examined in myeloma?
Bone marrow biopsy
703
What would serum and urine electrophoresis show in myeloma?
Shows monoclonal band or paraprotein
704
Give the four diagnostic criteria for myeloma.
- Monoclonal protein band in serum or urine electrophoresis - Plasma cells increased on marrow biopsy - Evidence of end-organ damage - Bone lesions
705
Give four supportive treatments for bone effects in myeloma.
- Analgesia - Bisphosphonates - Local radiotherapy - Orthopaedic procedures in vertebral collapse
706
Give three supportive treatments in myeloma which are not to do with bones.
- Correct anaemia (transfusion or EPO) - Rehydrate/dialysis for renal impairment - Treat infections rapidly (broad spectrum antibiotics)
707
Describe the treatment used for myeloma.
- Chemotherapy +/- steroids - Thalidomide reduces relapse - Autologous stem cell transplant
708
What is an autologous stem cell transplant?
The patient’s own stem cells are collected, then high dose chemotherapy is used to kill off all cancer cells. The patient’s own stem cells are then given back to them.
709
Describe the prognosis in myeloma.
All patients will eventually relapse, however survival can be prolonged by keeping disease in plateau phase. Could potentially be considered a chronic disease.
710
What is the main cause of death in myeloma?
Infections
711
Name five plasma cell dyscrasias.
- Myeloma - Solitary plasmocytoma - Multiple solitary plasmocytoma - Extramedullary plasmocytoma - Wadenstrom macroglobulinaemia
712
What antibody is produced in excess in Waldenstrom macroglobulinaemia?
IgM
713
What is monoclonal gammopathy of uncertain significance (MGUS)?
Paraprotein in the serum but no other signs of disease.
714
What is a paraprotein?
A protein found in the blood only as a result of cancer or other disease.
715
Define leukaemia.
Abnormal proliferation of white blood cells, which are mainly found in the blood.
716
What is abnormal proliferation of haemocytoblasts called?
Mixed lineage acute leukaemia
717
What is abnormal proliferation of common myeloid progenitors/myeloblasts called?
Acute myeloid leukaemia
718
What is abnormal proliferation of lymphoblasts called?
Acute lymphoblastic leukaemia
719
What is abnormal proliferation of B lymphocytes called?
Chronic lymphatic/lymphocytic leukaemia
720
What is abnormal proliferation of basophils/neutrophils/eosinophils called?
Chronic myeloid leukaemia
721
What is abnormal proliferation of monocytes called?
Chronic myelomonocytic leukaemia
722
Define acute lymphoblastic leukaemia.
Malignancy of lymphoid cells, affecting B or T lymphocyte cell lines.
723
What is the peak age for ALL?
0-4years
724
What causes ALL?
Thought to develop from genetic susceptibility + environmental trigger
725
Give two important associations with ALL.
- Ionising radiation (eg. X rays in pregnancy) | - Down’s syndrome
726
What do the blood tests show in ALL?
Blast cells | WCC usually high
727
What does the bone marrow aspirate show in ALL?
Blast cells
728
What may show up on CXR in ALL?
Mediastinal and abdominal lymphadenopathy
729
What does the lumbar puncture look for in ALL?
CNS involvement
730
What can be used to predict prognosis in leukaemia?
Cytogenetic chromosomal analysis and molecular genetics
731
What technique is used to determine the specific cells proliferating in leukaemia?
Immunophenotyping
732
What technique is used to detect minimal residual disease in leukaemia?
PCR
733
What are the signs/symptoms of ALL?
- Anaemia - Infections (neutropenia) - Bleeding - Hepatosplenomegaly - Lymphadenopathy - CNS involvement
734
What supportive treatments are used in leukaemia?
- Blood/platelet transfusion - IV fluids - Allopurinol (prevents tumour lysis syndrome) - Hickman line - Fertility cryopreservation (in AML)
735
What treatment can be given to combat infections in leukaemia?
- IV antibiotics | - Prophylactic antivirals, antifungals, antibiotics
736
What treatments are used in leukaemia?
- Chemotherapy - Clinical trials - Steroids
737
What type of transplant can be used in acute lymphoblastic leukaemia?
Matched related allogenic marrow transplantations
738
When is a patient with leukaemia said to be in remission?
No evidence of leukaemia in the blood, a normal or recovering blood count, and <5% blasts in a normal regenerating marrow.
739
What are the cure rates for adults and children with ALL?
``` Children = 70-90% Adults = 40% ```
740
Name two sanctuary sites for ALL.
- Brain | - Testes
741
Define acute myeloid leukaemia.
Neoplastic proliferation of marrow myeloid blast cells.
742
Describe the rate of onset of AML.
Pregresses rapidly, start treatment immediately.
743
What is the peak age for AML?
85-89 years
744
Give four associations with AML.
- Long-term complication of chemotherapy - Radiation - Down’s syndrome - Preceding haematological disorders
745
Give seven signs/symptoms of AML.
- Anaemia - Infection - Bleeding - Hepatosplenomegaly - Gum hypertrophy - Skin involvement - CNS involvement rare at presentation
746
Describe the WCC in AML.
Often high but can be normal or low.
747
Why is a bone marrow biopsy required in AML?
Blast cells may be few in the peripheral blood.
748
Give a feature seen on a blood film that is diagnostic of AML.
Auer rods
749
Describe the chemotherapy used for AML.
- Very intensive | - Less intensive (non-curative) for older patients, delivered on outpatient basis
750
When is a bone marrow transplant indicated in AML?
1st remission with poor prognosis
751
Give a complication of a bone marrow transplant.
Graft vs host disease
752
Describe the prognosis for AML compared to ALL.
Lower relapse rates but significant mortality.
753
Define chronic myeloid leukaemia.
Uncontrolled proliferation of myeloid cells.
754
What is the peak age of CML?
40-60years
755
Describe the chromosome associated with CML.
``` Philadelphia chromosome (t9;22) - Forms 210kDa fusion protein and constantly activated tyrosine kinase ```
756
Give some symptoms of CML.
- Weight loss - Tiredness - Fever - Sweats - May be features of gout - Bleeding - Abdominal discomfort
757
Give four signs of CML.
- Splenomegaly - Hepatomegaly - Anaemia - Bruising
758
What is the WCC in CML?
Very high (whole spectrum of myeloid cells)
759
What is the Hb level in CML?
Low or normal
760
What is the urate and B12 levels in CML?
High
761
Describe the appearance of the bone marrow sample in CML.
Hypercellular
762
What is the treatment for CML?
- Tyrosine kinase inhibitors | - Allogenic stem cell transplant
763
Describe the three phases of CML.
- Chronic phase - few symptoms - Accelerated phase - increasing symptoms - Blast transformation - acute leukaemia
764
What is the median survival time in CML?
5-6years
765
Define chronic lymphocytic leukaemia.
Accumulation of mature B cells that have escaped programmed cell death and undergone cell cycle arrest.
766
What are the symptoms of CLL?
- Often none - May be anaemic or infection-prone - If severe: weight loss, sweats, anorexia
767
What are three signs of CLL?
- Enlarged, rubbery, non-tender lymph nodes - Splenomegaly - Hepatomegaly
768
What will the lymphocyte count be in CLL?
High
769
Describe the blood test results in later stage CLL.
- Low Hb - Low neutrophils - Low platelets - Autoimmune haemolysis
770
What is death commonly due to in CLL?
Infection or transformation to aggressive lymphoma.
771
Describe the likelihood and rate of progression in CLL.
- 1/3 never progress - 1/3 progress slowly - 1/3 progress actively
772
When are drugs used to treat CLL?
- Symptomatic - Immunoglobulin genes are mutated - 17p deletions
773
What can be given to help autoimmune haemolysis in CLL?
Steroids
774
What can be used to treat lymphadenopathy and splenomegaly in CLL?
Radiotherapy
775
Give two forms of supportive treatment in CLL.
- Transfusions | - IV human Ig if recurrent infection
776
Name five complications of leukaemia.
- Neutropenia - Tumour lysis syndrome - Hyperviscosity - DIC - Sepsis
777
Describe tumour lysis syndrome.
Massive destruction of (tumour) cells (in chemotherapy), leading to increased potassium, increased urate, and renal injury.
778
What can be used to prevent tumour lysis syndrome?
High fluid intake and allopurinol.
779
Why is hyperviscosity dangerous?
If WCC very high thrombi may form in brain, lung, and heart (leukostasis).
780
Define lymphoma.
Malignant proliferation of lymphocytes, predominantly in the lymph nodes.
781
Where can lymphoma appear?
- Lymph nodes - Blood - Bone marrow - Liver - Spleen - Anywhere
782
What are most cases of lymphoma caused by?
We don’t know
783
Give four things that can cause lymphoma.
- Primary immunodeficiency - Secondary immunodeficiency (HIV, transplant) - Infection (EBV, HTLV-I, helicobacter pylori) - Autoimmune disorders
784
Give four ways that lymphoma can present.
- Nodal disease - Extranodal disease - Compression syndromes - Systemic (B) symptoms
785
What are the nodal signs of lymphoma?
Enlarged lymph nodes
786
What are the extranodal signs of lymphoma?
Hepatosplenomegaly
787
Give three systemic (B) symptoms of lymphoma.
- Loss of appetite - Weight loss - Night sweats
788
What diagnostic investigations are done in lymphoma?
- Lymph node biopsy - Blood tests/film - Scans - Bone marrow biopsy - Immunophenotyping - Cytogenetic analysis (karyotype, FISH) - Molecular techniques (PCR)
789
What staging investigations are carried out in lymphoma?
- Blood tests - CT scan - Bone marrow biopsy - PET scans
790
Give four differential diagnoses of neck lumps.
- Reactive lymph nodes - Malignant - Arising from underlying neck structures - Embryological remnant
791
Give two causes of reactive lymph nodes.
- Infective (bacterial, viral, TB) | - Inflammatory
792
Give three causes of malignant lymph nodes.
- Lymphoma - Metastatic - Primary head and neck
793
How can you tell the difference between reactive and malignant lymph nodes?
Reactive lymph nodes are tender and shrink with time.
794
Where does Hodgkin’s lymphoma manifest?
Lymph nodes
795
What is the peak age for Hodgkin’s lymphoma?
20-24 years and elderly
796
Describe the presentation of Hodgkin’s lymphoma.
- Painless lymphadenopathy | - B symptoms (sweats, weight loss)
797
What is the diagnostic criteria for Hodgkin’s lymphoma?
Reed-Sternberg cells are present
798
Describe stage I Hodgkin’s lymphoma.
Present in one group of lymph nodes.
799
Describe stage II Hodgkin’s lymphoma.
Present in multiple groups of lymph nodes on the same side of the diaphragm.
800
Describe stage III Hodgkin’s lymphoma.
Present in multiple groups of lymph nodes on both sides of the diaphragm.
801
Describe stage IV Hodgkin’s lymphoma.
Present in organs outside the lymph nodes.
802
As well as staging having a number, how else is Hodgkin’s lymphoma classified?
A (absence of symptoms) or B (presence of B symptoms)
803
Describe the treatment for stage 1-2A Hodgkin’s lymphoma.
Short course combination chemotherapy followed by radiotherapy.
804
Describe the treatment for stage 2B-4 Hodgkin’s lymphoma.
Combination chemotherapy
805
What is used to treat a relapse in Hodgkin’s lymphoma?
Autologous bone marrow transplant.
806
What are the chances of long term survival in Hodgkin’s lymphoma?
Good
807
Where does Non-Hodgkin’s lymphoma manifest?
Anywhere
808
Describe the cells in Non-Hodgkin’s lymphoma.
- No Reed-Sternberg cells | - More commonly derived from B cells
809
Give an example of a low grade Non-Hodgkin lymphoma.
Follicular lymphoma
810
At what age does Non-Hodgkin’s lymphoma usually present?
60-70years
811
Describe the growth rate and appearance at presentation of low grade Non-Hodgkin’s lymphoma.
Slow growing | Usually advanced at presentation
812
What is the median survival time in Non-Hodgkin’s lymphoma?
9-11 years
813
How is Non-Hodgkin’s lymphoma cured?
It is incurable.
814
Give nine treatment options for low grade Non-Hodgkin’s lymphoma.
- Do nothing - Alkylating agents - Combination chemotherapy - Purine analogues - Monoclonal antibodies - Radio-immunoconjugates - New oral targeted agents - Radiotherapy - Bone marrow transplant
815
Give an example of a high grade Non-Hodgkin lymphoma.
Diffuse large B cell lymphoma
816
How do high grade Non-Hodgkin’s lymphoma usually present?
Nodal presentation
817
Describe the typical history in high grade Non-Hodgkin’s lymphoma.
Patient usually unwell with a short history.
818
What is the treatment for early high grade Non-Hodgkin’s lymphoma?
Short course chemotherapy + radiotherapy
819
What is the treatment for advanced high-grade Non-Hodgkin’s lymphoma?
Combination chemotherapy + monoclonal antibodies
820
Give an example of a very high grade non-Hodgkin’s lymphoma.
Burkitt’s lymphoma
821
In which age is Burkitt’s lymphoma relatively common?
Children
822
How does Burkitt’s lymphoma commonly present?
Swelling in the neck and jaw.
823
Name a monoclonal antibody used in lymphoma.
Rituximab
824
What does rituximab target?
CD20 on B cells
825
How does radio-immunotherapy work?
Involves using monoclonal antibodies to deliver drugs directly to cancer cells.
826
Briefly describe the concept of T cell engaging therapy.
A bi-specific antibody which binds to CD19 on B cells and CD3 on T cells to join T cells with tumour B cells.
827
Describe the inheritance pattern in sickle cell anaemia.
Autosomal recessive
828
What is the amino acid change in sickle cell anaemia?
Glu replaced by Val
829
Describe the haemoglobin which is produced in sickle cell anaemia.
HbS instead of HbA
830
Briefly describe the abnormality in Hb in sickle cell anaemia.
Abnormal production of b globin chains.
831
Briefly describe the pathogenesis of sickle cell anaemia.
HbS polymerises when deoxygenated. This causes RBCs to deform. Sickle cells are fragile and haemolyse, and also block small vessels.
832
Which group of patients is sickle cell anaemia more common in?
Patients of African origin
833
What is the advantage of having sickle cell trait?
It causes no disability and protects from falciparum malaria
834
What is the reticulocyte count in sickle cell anaemia?
Increased
835
Describe the bilirubin levels in sickle cell anaemia.
Increased
836
What is seen on a blood film in sickle cell anaemia?
Sickle cells and target cells.
837
Name a test that can be used to diagnose sickle cell anaemia.
Hb electrophoresis
838
What causes a vaso-occlusive crisis in sickle cell anaemia?
Microvascular occlusion
839
What can trigger a sickle cell anaemia vaso-occlusive crisis?
- Cold - Dehydration - Infection - Hypoxia
840
Give seven consequences of a sickle cell anaemia vaso-occlusive crisis.
- Mesenteric ischaemia - Dactylitis - Stroke - Seizures - Cognitive defects - Avascular necrosis - Leg ulcers
841
What causes a sickle cell anaemia aplastic crisis?
Parvovirus B19
842
What happens in a sickle cell anaemia aplastic crisis?
Sudden reduction in bone marrow production.
843
How is a sickle cell anaemia aplastic crisis treated?
It is usually self-limiting.
844
What is a sickle cell anaemia sequestration crisis?
Pooling of blood in the spleen +/- liver.
845
Give three consequences of a sickle cell anaemia sequestration crisis.
- Organomegaly - Severe anaemia - Shock
846
In which age range do sickle cell anaemia sequestration crises most commonly occur?
Children
847
How are sickle cell anaemia sequestration crises usually treated?
Urgent transfusion
848
Describe sickle cell anaemia acute chest syndrome.
Pulmonary infiltrates involving complete lung segments.
849
Give five symptoms of sickle cell anaemia acute chest syndrome.
- Pain - Fever - Tachypnoea - Wheeze - Cough
850
Give a consequence of sickle cell anaemia acute chest syndrome.
Pulmonary hypertension
851
Give 11 complications of sickle cell anaemia.
- Splenic infarction - Poor growth - Chronic renal failure - Gall stones - Retinal disease - Iron overload - Lung damage - Priapism - Infections - Renal impairment - Joint damage
852
Describe the management of sickle cell anaemia.
- Hydroxycarbamide if frequent crises - Prophylaxis (antibiotics/immunisation) if splenic infarction - Bone marrow transplant (curative but controversial)
853
How does hydroxycarbamide reduce sickle cell anaemia crises?
Increases foetal Hb in the blood, resulting in less sickle cells.
854
Define thalassaemia.
Globin chain disorders resulting in diminished synthesis of one or more globin chains with consequent reduction in the haemoglobin.
855
Which thalassaemia is usually caused by gene deletions?
A-thalassaemia
856
Which type of thalassaemia is usually caused by gene mutations?
B-thalassaemia
857
How many genes, and on which chromosome/s, control a-globin production?
Four genes, chromosomes 11 and 16
858
How many genes, and on which chromosome/s, control b-globin production?
Two genes, on chromosome 11
859
Describe the mechanism os haemolysis in thalassaemia.
The dominant chain precipitates, damaging the RBC membrane and causing haemolysis.
860
What are the three classifications of b-thalassaemia?
Thalassaemia Major Thalassaemia Intermedia Thalassaemia Carrier/heterozygote
861
Describe thalassaemia major.
Transfusion dependent
862
Describe thalassaemia intermedia.
Less severe anaemia and can survive without regular blood transfusions.
863
Describe thalassaemia carrier.
Asymptomatic
864
What is the most common age at presentation of b-thalassaemia major?
6-12months
865
Give four signs of b-thalassaemia major.
- Failure to feed - Listless (lacking energy) - Crying - Pale
866
What is the level of Hb in b-thalassaemia major?
Low
867
Describe the MCV and MCH in b-thalassaemia major.
Very low
868
Describe the appearance of RBCs in b-thalassaemia major.
Some large and some small (irregular) Very pale Some nucleated
869
Describe the level of HbF in a neonatal sample of a patient with b-thalassaemia major.
HbF >90%
870
Describe the ferritin in b-thalassaemia major.
Normal
871
Give three complications of b-thalassaemia major.
- Abnormal bone growth - Failure to meet milestones - Osteoporosis
872
Give three treatment methods used in b-thalassaemia major.
- Blood transfusion - Iron chelators (prevent iron overload) - Ascorbic acid (increase urinary excretion of iron)
873
What is the a-thalassaemia status in a person with one or two deleted genes?
Carrier
874
What is the a-thalassaemia status of a person with 3 deleted genes?
Causes moderate or severe disease (HbH)
875
What is the a-thalassaemia status in a person with four deleted genes?
Bart’s hydrops foetalis. Severe oedema in the foetus/newborn. Death usually occurs in utero or shortly after birth.
876
Describe the globin chains making up Hb in Bart’s Hydrops foetalis.
Four gamma chains
877
Describe the typical inheritance pattern for RBC membranopathies .
Autosomal dominant
878
Name the two most common RBC membranopathies.
Spherocytosis and elliptocytosis
879
What causes RBC membranopathies?
Deficiency of red cell membrane proteins caused by a variety of genetic lesions.
880
Give two consequences of RBC membranopathies.
Neonatal jaundice | Mild/moderate haemolytic anaemia
881
How are RBC membranopathies treated?
- Folic acid - Splenectomy - Vaccinations (due to splenectomy)
882
Briefly describe what happens in mild RBC membranopathies.
Compensated haemolysis. | Increased reticulocytes.
883
Briefly describe the signs of moderate/severe membranopathies.
Splenomegaly in childhood and gallstones.
884
Name the glycolysis pathway which provides energy for RBCs.
Embden-Meyerhof pathway
885
What is the two consequence of inherited RBC enzyme deficiencies?
- Shortened red cell lifespan from oxidative damage
886
What are the symptoms in G6PD deficiency?
Most are asymptomatic
887
Name three things that occur in a G6PD deficiency crisis.
- Haemolysis - Jaundice - Anaemia
888
Name three factors which precipitate a G6PD deficiency crisis.
- Broad beans - Infection - Drugs
889
How are G6PD deficiency crises usually treated?
They are usually self-limiting.
890
What is the inheritance pattern in pyruvate kinase deficiency?
Autosomal recessive
891
What factor can cause an aplastic crisis in pyruvate kinase deficiency?
Parvovirus B19 infection
892
How is pyruvate kinase deficiency treated?
- Folic acid - Transfuse in severe crisis - Splenectomy in high transfusion requirements
893
Give five causes of bleeding.
- Injury - Vascular disorders - Low platelets - Abnormal platelet function - Defective coagulation
894
Give four clinical features of platelet dysfunction.
- Mucosal bleeding (epistaxis, gum bleeding menorrhagia) - Easy bruising - Petechiae, purpura - Traumatic haematomas
895
Give four acquired causes of low platelets to do with production failure.
- Drugs - Marrow suppression - Marrow failure - Marrow replacement
896
Give three causes of low platelets to do with increased removal.
- Immune - Consumption - Splenomegaly
897
Give an artefactual cause of low platelets.
EDTA induced clumping
898
Give two congenial causes of impaired platelet function.
- Platelet disorders | - von Willebrand disease
899
Give three platelet disorders causing impaired function.
- Storage pool disorders - Glanzmann (reduction/deficiency of GPIIb/IIIa) - Bernard Soulier (reduction/deficiency of GP1b)
900
Give two acquired causes of impaired platelet function.
- Uraemia | - Antiplatelet drugs
901
Give a congenital cause of thrombocytopenia due to decreased production.
Absent/reduced/malfunctioning megakaryocytes in bone marrow.
902
Give five causes of thrombocytopenia due to decreased production due to infiltration of bone marrow.
- Leukaemia - Metastatic malignancy - Lymphoma - Myeloma - Myelofibrosis
903
Give six causes of reduced platelet production by the bone marrow.
- Low B12/folate - Reduced TPO (liver disease) - Medication (chemotherapy) - Toxins (alcohol) - Infections (HIV, TB) - Anaplastic anaemia
904
Give a cause of dysfunctional production of platelets in the bone marrow.
Myelodysplasia
905
Give two causes of hypersplenism.
- Portal hypertension | - Splenomegaly
906
What is a consequence of hypersplenism?
Thrombocytopenia due to increased removal
907
Give five causes of consumption of platelets which causes thrombocytopenia.
- DIC - TTP - haemolytic uraemia syndrome (HUS) - Haemolysis, elevated liver enzymes, and low platelets (HELLP) - Major haemorrhage
908
How does aspirin affect platelet function?
Irreversibly inhibits COX1
909
How does clopidogrel affect platelet function?
Blocks P2Y12 ADP receptor
910
How does Tirofiban affect platelet function?
Blocks GPIIb/IIIa
911
What is immune thrombocytopenia (ITP)?
IgG antibodies form to platelet and megakaryocyte surface glycoproteins. Opsonised platelets are removed by the reticuloendothelial system.
912
When does primary immune thrombocytopenia develop?
Following viral infection or immunisation.
913
When does secondary immune thrombocytopenia develop?
In association with some malignancies (CLL) and infections (HIV, HepC)
914
How is immune thrombocytopenia diagnosed?
- Look for underlying cause | - Diagnosis of exclusion
915
Give four treatment options for immune thrombocytopenia.
- Immunosuppression (steroids) - Treat underlying cause - If bleeding give platelets (will disappear quickly) - Tranexamic acid (inhibits fibrin breakdown)
916
Describe what happens in disseminated intravascular coagulation.
- Cytokine release in response to SIRS - Systemic activation of clotting cascade - Microvascular thrombosis and organ failure - Consumption of platelets and clotting factors - Bleeding
917
Describe the fibrinogen and d dimer levels in DIC.
Low fibrinogen | High D dimer
918
What does D dimer represent?
Fibrin degradation products
919
What is the treatment for DIC?
- Treat underlying cause | - Supportive provision of platelets, clotting factors, fibrinogen
920
Describe thrombotic thrombocytopenic purpura (TTP).
Spontaneous platelet aggregation in microvasculature (brain, kidney, heart). It is a medical emergency.
921
Briefly describe what causes thrombotic thrombocytopenic purpura.
Reduction in protease enzyme ADAMTS13 which usually breaks down vWF multimers. Acquired TTP is due to antibodies against ADAMTS13.
922
Give four consequences of thrombotic thrombocytopenic purpura.
- Consumption of platelets - Microangiopathic haemolytic anaemia - Renal/CNS/cardiac impairment - Fever
923
Why aren’t platelets given in thrombotic thrombocytopenic purpura?
They increase thrombosis
924
What are two treatments for TTP?
- Urgent plasma exchange (replaces ADAMTS13 and removes antibody) - Immunosuppression (reduce antibody levels)
925
Define anaemia.
Low haemoglobin concentration
926
Give two circumstances in the body which could cause a low haemoglobin concentration.
- Decreased red blood cell mass | - Increased plasma volume
927
Give two processes which can causes a low red blood cell mass.
- Low production | - High rate of removal
928
Define a low haemoglobin concentration for men and women.
Men <135g/L | Women <115g/L
929
What is a normal MCV?
Between 80 and 100fL
930
Give two general consequences of anaemia.
- Reduced oxygen transport | - Tissue hypoxia
931
Give three compensatory changes which occur in anaemia.
- Increased tissue perfusion - Increased oxygen transfer to tissues - Increased red cell production
932
Give five pathological consequences of anaemia.
- Myocardial fatty change - Fatty change in liver - Aggravate angina/claudication - Skin and nail atrophic changes - CNS cell death
933
What are the symptoms of anaemia?
- Fatigue - Dyspnoea - Faintness - Palpitations - Headache - Tinnitus - Anorexia - Angina (if there is pre-existing IHD)
934
Give four signs of anaemia.
- Pallor (eg. Conjunctivae) - Hyperdynamic circulation (tachycardia, flow murmurs, cardiac enlargement) - Retinal haemorrhages - Heart failure (late stages)
935
Are the signs of anaemia always present?
No - they might be absent, even in severe anaemia.
936
Give the three general categories of anaemia.
- Microcytic - Normocytic - Macrocytic
937
Describe the size of the cells in microcytic anaemia.
Small
938
Describe the size of the cells in normocytic anaemia.
Normal
939
Describe the size of the cells in macrocytic anaemia.
Large
940
In general, what is microcytic anaemia caused by?
Failure to produce haemoglobin.
941
Give three causes of microcytic anaemia.
- Iron deficiency - Chronic disease - Thalassaemia
942
Give three causes of normocytic anaemia.
- Acute blood loss - Anaemia of chronic disease - Combined haematinic deficiency
943
Give three causes of macrocytic anaemia.
- B12 or folate deficiency - Alcohol excess or liver disease - Hypothyroidism
944
Give four haematological causes of macrocytic anaemia.
- Chemotherapy - Haemolysis - Bone marrow failure - Bone marrow infiltration
945
Give four causes of iron deficiency anaemia.
- Blood loss - Poor diet - Malabsorption - Hookworm (GI blood loss)
946
Give four (rare) signs of iron deficiency anaemia.
- Koilonychia (spoon nails) - Atrophic glossitis - Angular cheilosis (inflammation of the corners of the mouth) - Post-cricoid webs (membranes of the oesophagus)
947
Describe the test results expected in iron deficiency anaemia.
- Microcytic - Hypochromic (pale RBCs) - Anisocytosis (RBCs unequal size) - Poikilocytosis (variation in cell shape) - Low MCV - Low MCH - Low MCHC - Confirmed by low ferritin
948
Describe the treatment for iron deficiency anaemia.
- Treat cause | - Oral iron (ferrous sulfate)
949
Give the three problems which cause anaemia of chronic disease.
- Poor use of iron in erythropoiesis - Cytokine-induced shortening of RBC survival - Decreased production and response to erythropoietin
950
Describe the test results expected in anaemia of chronic disease.
- Normocytic anaemia | - Ferritin normal or raised
951
Describe the treatment for anaemia of chronic disease.
- Treat underlying disease more vigorously | - Erythropoietin
952
What is a megaloblast?
A cell in which nuclear maturation is delayed compared with the cytoplasm.
953
Why does megaloblastic anaemia occur with B12 and folate deficiency?
They are both required for DNA synthesis.
954
Describe where folate is found, and how it is absorbed.
- Found in green vegetables, nuts, yeast, and liver - Synthesised by gut bacteria - Absorbed by duodenum/proximal jejunum
955
Give four causes of folate deficiency.
- Poor diet - Increased demand (pregnancy, increased cell turnover) - Malabsorption - Drugs/alcohol
956
What is the treatment for folate deficiency?
- Assess for underlying cause | - Treat with folic acid (and B12, unless patient known to have normal B12 level)
957
Describe where B12 is found and how it is absorbed.
- Found in meat, fish, and dairy products | - Binds to intrinsic factor in the stomach and absorbed in the terminal ileum
958
Give two causes of B12 deficiency.
- Dietary | - Malabsorption (stomach or terminal ileum)
959
What is pernicious anaemia?
A type of megaloblastic anaemia caused by autoimmune atrophic gastritis, leading to lack of intrinsic factor.
960
What are the features of B12 deficiency?
- Symptoms of anaemia - ‘Lemon tinge’ to skin (pallor + jaundice) - Glossitis - Angular cheilosis (sore corners of mouth) - Irritability - Depression - Psychosis - Dementia - Parasthesiae - Peripheral neuropathy - Subacute combined degeneration of the spinal cord
961
What is the treatment for B12 deficiency?
- Treat cause | - Injections of B12 if due to malabsorption
962
Define polycythaemia.
Proliferation of a clone of haematopoietic myeloid stem cells (RBCs).
963
What is relative polycythaemia?
Decreased plasma volume with normal red blood cell mass.
964
What is absolute polycythaemia?
Increased red blood cell mass.
965
What are some reactive/secondary causes of polycythaemia?
- Smoking - Lung disease - Cyanotic heart disease - Altitude - EPO/androgen excess
966
What causes primary polycythaemia?
Polycythaemia Rubra Vera
967
Briefly describe the pathogenesis of polycythaemia rubra vera.
Malignant proliferation of a clone derived from one pluripotent marrow stem cell. (Excess proliferation of RBCs, and often also WBCs and platelets)
968
Which mutation is present in >90% people with polycythaemia rubra vera?
JAK2
969
Describe the symptoms of polycythaemia rubra vera.
- May be asymptomatic (detected on FBC) - Vague signs due to hyperviscosity - Itch after a hot bath - Erythromelalgia (intense burning in fingers and toes)
970
Give four symptoms of hyperviscosity.
- Headaches - Dizziness - Tinnitus - Visual disturbance
971
Give four signs of polycythaemia rubra vera.
- Facial plethora - Splenomegaly - Gout (increased urate from RBC turnover) - Features of arterial or venous thrombosis
972
What would the FBC show in polycythaemia rubra vera?
- Increased RCC - Increased Hb - Increased HCT - Increased PCV - Increased WCC - Increased platelets
973
What U and E measurement would be increased in polycythaemia rubra vera?
B12
974
What would the bone marrow sample show in polycythaemia rubra vera?
Hypercellularity with erythroid hyperplasia.
975
What would the neutrophil alkaline phosphatase score be in polycythaemia rubra vera?
High
976
What would the level of serum erythropoietin be in polycythaemia rubra vera?
Low
977
What would the results of a radioactive chromium study show in polycythaemia rubra vera?
Raised red cell mass
978
What is the aim of treatment in polycythaemia rubra vera?
Keep HCT <45% to reduce thrombosis risk.
979
What are the treatment options for polycythaemia rubra vera?
- Venesection (younger patients, low risk) - Hydroxycarbamide - Low dose aspirin
980
Give four complications of polycythaemia rubra vera.
- Increased plasma viscosity - Thrombosis - 30% transition to myelofibrosis - 5% transition to acute leukaemia
981
Define neutrophilia.
Too many white blood cells (neutrophils).
982
What are the reactive causes of neutrophilia?
- Infection - Inflammation - Malignancy
983
Give a primary cause of neutrophilia.
Chronic myeloid leukaemia
984
Define neutropaenia.
Not enough neutrophils.
985
What level does neutropaenia have to be at to be classed as severe?
<0.5
986
Give the causes of neutropaenia related to underproduction.
- Marrow failure - Marrow infiltration - Toxicity (drugs)
987
Give the causes of neutropaenia related to increased removal.
- Autoimmune - Felty’s syndrome - Cyclical
988
Define lymphocytosis.
Too many white blood cells (lymphocytes)
989
Give some secondary causes of lymphocytosis.
- Infection - Inflammation - Malignancy
990
Give a primary cause of lymphocytosis.
Chronic lymphocytic leukaemia
991
Define thrombocytopaenia.
Not enough platelets
992
Define thrombocytosis.
Too many platelets
993
Give some secondary causes of thrombocytosis.
- Infection - Inflammation - Malignancy
994
Give a primary cause of thrombocytosis.
Essential thrombocythaemia
995
What is an arrhythmia?
A disturbance of cardiac rhythm.
996
What are the cardiac causes of arrhythmias?
- MI - Coronary artery disease - Left ventricle aneurysm - Mitral valve disease - Cardiomyopathy - Pericarditis - Myocarditis - Aberrant conduction pathways
997
What are the non-cardiac causes of arrhythmias?
- Caffeine - Smoking - Alcohol - Pneumonia - Drugs - Metabolic imbalance - Phaeochromocytoma
998
Describe the presentation of arrhythmias.
- Palpitation - Chest pain - Presynsope/syncope - Hypotension - Pulmonary oedema - Some may be asymptomatic
999
What factors should be asked when taking a history of arrhythmias?
- Detailed history of palpitations - Precipitating factors - Onset/offset - Nature - Duration - Associated symptoms - Drug history - Past medical history - Family history
1000
Define acute limb ischaemia.
Limb ischaemia which has a rapid onset.
1001
Why do symptoms develop in peripheral vascular disease?
There is an oxygen supply-demand mismatch when exercising.
1002
Give the three stages of peripheral vascular disease.
1. Stress-induced physiological malfunction 2. Structural and functional breakdown 3. Infarction
1003
What is amaurosis fugax?
Transient monocular blindness, which may be the result of a thrombus in the retinal artery.
1004
Briefly describe the pathophysiology of gallstones.
Stones which form in the gallbladder, 70% cholesterol, 30% pigment, +/- calcium
1005
Give three risk factors for gallstones.
- Female - Fat - Fertile
1006
What are the symptoms of gallstones?
- Most are asymptomatic - May have signs of cholangitis - May have biliary colic
1007
What is biliary colic?
Sudden, severe pain due to a gallstone temporarily blocking the cystic duct.
1008
Does biliary pain occur in gallstones which are located in the: A) gallbladder B) bile duct
A) Yes | B) Yes
1009
Does cholecystitis occur when gallstones are located in: A) Gallbladder B) Bile duct
A) Yes | B) No
1010
Does obstructive jaundice occur when gallstones are located in the: A) Gallbladder B) Bile duct
A) Maybe | B) Yes
1011
How can obstructive jaundice occur when gallstones are stuck in the gallbladder?
The stone in the gallbladder can compress the bile duct from the outside.
1012
Does cholangitis occur when gallstones are located in the: A) gallbladder B) bile duct
A) No | B) yes
1013
Does pancreatitis occur when gallstones are located in the: A) Gallbladder B) Bile duct
A) No | B) Yes
1014
What investigations would be carried out in gallstones?
- Serum bilirubin, albumin, PTT - Cholestatic and hepatocellular enzymes - Viral markers - Ultrasound
1015
Describe the serum levels of ALT in gallstones.
Often high initially then rapidly falls.
1016
What is the management for gallstones in the gallbladder?
- Laporoscopic cholecystectomy | - Bile duct dissolution therapy
1017
What is the management for gallstones in the bile duct?
- Endoscopic retrograde cholangio-pancreatography (ERCP) | - Surgery for large stones
1018
What is cholecystitis?
Inflammation of the gallbladder.
1019
What is the most common cause of cholecystitis?
A gallstone blocking the cystic duct.
1020
What are the symptoms of acute cholecystitis?
- Continuous epigastric or RUQ pain - Vomiting - Fever - Local peritonitis - Gallbladder mass
1021
What will the investigations show in acute cholecystitis?
- Murphy’s sign positive - Increased WCC - Ultrasound (pericholecystic fluid and stones)
1022
Describe Murphy’s sign.
Lay two fingers over the RUQ and ask the patient to breathe in. This causes pain and arrest in inspiration as inflamed GB impinges on fingers.
1023
What is the treatment for cholecystitis?
- Nil by mouth - Pain relief - Antibiotics - Laparoscopic cholecystectomy
1024
What is chronic cholecystitis?
Chronic inflammation of the gallbladder, +/- colic
1025
What are the symptoms of chronic cholecystitis?
- Flatulent dyspepsia - Vague abdominal discomfort - Distension - Nausea - Flatulence - Fat intolerance
1026
What investigation should be carried out in chronic cholecystitis?
Ultrasound
1027
What is the treatment for chronic cholecystitis?
Cholecystectomy
1028
What is biliary colic?
Gallstones which are symptomatic with cystic duct obstruction.
1029
What are the symptoms of biliary colic?
- RUQ pain | - May have jaundice
1030
What is the treatment for biliary colic?
- Analgesia - Rehydrate - Nil by mouth - Elective laparoscopic cholecystectomy
1031
What is ascending cholangitis?
Bile duct infection caused by bacteria ascending from the duodenum. Tends to occur if the bile duct is already partially obstructed by gallstones.
1032
What are the symptoms of ascending cholangitis?
- RUQ pain - Jaundice - Rigors
1033
What is the treatment for ascending cholangitis?
Antibiotics
1034
What are the three elements that make up Charcot’s Triad?
- Jaundice - RUQ pain - Fever
1035
Which of the elements of Charcot’s triad are present in biliary colic?
- RUQ pain
1036
Which of the elements of Charcot’s Triad are present in acute cholecystitis?
- RUQ pain | - Fever
1037
Which of the elements of Charcot’s triad are present in ascending cholangitis?
- RUQ pain - Fever - Jaundice
1038
Briefly describe acute suppurative cholangitis.
The presence of pus in the biliary ducts, resulting in Reynold’s Pentad: Charcot’s Triad plus hypotension and confusion.
1039
Define cirrhosis.
Irreversible replacement of the normal liver architecture by bands of fibrous tissue separating nodules of regenerating hepatocytes.
1040
What are the common causes of cirrhosis?
- Chronic alcohol abuse | - Hepatitis B/C
1041
Give seven less common causes of cirrhosis.
- Haemochromatosis - a1-antitrypsin deficiency - Wilson’s disease - Hepatic vein events - Non-alcoholic steatohepatitis - Autoimmunity - Drugs
1042
Give some signs of chronic liver disease which may also indicate cirrhosis.
- Leukonychia (white nails) - Terry’s nails (white proximally but reddened distally) - Clubbing - Palmar erythema - Hyperdynamic circulation - Dupuytren’s contracture (fingers permanently flexed) - Spider naevi - Xanthelasma (yellow plaques around eyes) - Gynaecomastia - Atrophic testes - Loss of body hair - Parotid enlargement - Hepatomegaly - Small liver (in late disease)
1043
What are some complications of hepatic failure?
- Coagulopathy - Encephalopathy - Hypoalbuminaemia - Sepsis - Spontaneous bacterial peritonitis - Hypoglycaemia
1044
What are three complications of portal hypertension?
- Ascites - Splenomegaly - Varices
1045
What is the treatment for cirrhosis?
Liver transplant is the only definitive treatment.
1046
What are oesophageal varices?
Extremely dilated sub-mucosal collateral veins in the lower third of the oesophagus.
1047
What are varices most commonly a consequence of?
Portal hypertension, due to cirrhosis.
1048
Give four risk factors for oesophageal varices.
- Cirrhosis - Severe liver disease - Alcohol abuse - Portal hypertension
1049
What investigations should be carries out if oesophageal varices are suspected?
- LFTs | - Endoscopy
1050
What is a potential complication of oesophageal varices?
If they rupture they can cause life-threatening bleeding.
1051
What is a potential treatment for oesophageal varices?
Variceal banding
1052
What is ascites?
Accumulation of fluid within the abdomen.
1053
Give five causes of ascites.
- Portal hypertension - Chronic liver disease - Neoplasia - Pancreatitis - Cardiac causes
1054
Briefly describe the pathogenesis of ascites.
- Systemic vasodilation (compensatory for increased portal venous pressure) leads to increased secretion of renin, NAd, vasopressin - Therefore there is more fluid retention - Increased intrahepatic resistance also leads to portal hypertension - Increased flow further increases pressure in the portal vein, leading to ascites - Low serum albumin also plays a role in not reabsorbing fluid
1055
What is the management for ascites?
- Fluid and salt restriction - Diuretics - Large volume paracentesis - Albumin - Trans-jugular intrahepatic portosystemic shunt (TIPS)
1056
Describe the histologic appearance of the hepatocytes in alcoholic liver disease.
Hepatocyte ballooning occurs, and fat droplets accumulate within hepatocytes.
1057
What cells mediate the damage and hepatocyte ballooning in alcoholic liver disease?
Neutrophils
1058
What protein might accumulate in hepatocytes injured by alcohol?
A cytoskeletal protein called Mallory’s hyalin
1059
Why does steatosis occur in alcoholic liver disease?
Alcohol changes the way that hepatocytes metabolise and produce fat.
1060
Where in the hepatic acinus does fibrosis typically occur in alcoholic liver disease?
Zone 3
1061
Can alcoholic fatty liver reverse?
Yes, by ceasing drinking
1062
What are the three stages of alcoholic liver disease?
- Steatosis - Alcoholic steatohepatitis - Cirrhosis
1063
What is the main cause of liver death in the UK?
Alcoholic liver disease
1064
What is the 10 year survival rate in alcoholic liver disease?
25%
1065
What is the treatment for alcoholic liver disease?
Liver transplant
1066
Give three causes of portal hypertension.
- Cirrhosis - Fibrosis - Portal vein thrombosis
1067
Give the two elements of the pathophysiology of portal hypertension.
- Increased hepatic resistance | - Increased splanchnic blood flow
1068
Give two consequences of portal hypertension.
- Varices | - Splenomegaly
1069
Give three causes of hepatic vein occlusion.
- Thrombosis (Budd-Chiari syndrome) - Membrane obstruction - Veno-occlusive disease
1070
Briefly describe the pathophysiology of hepatic vein occlusion.
- Congestion causes acute or chronic liver injury | - Back pressure leads to portal hypertension
1071
Describe what would be found on a biopsy in hepatic vein occlusion.
- Terminal or central veins become occluded by fibrous tissue - May be dilated sinusoids and haemorrhage
1072
Describe the presentation of hepatic vein occlusion.
- Abnormal liver tests - Ascites - Acute liver failure
1073
What is the treatment for hepatic vein occlusion?
- Anticoagulation - Transjugular intrahepatic portosystemic shunt - Liver transplantation
1074
What is acute-on-chronic liver failure?
Decompensation of a chronic liver disease.
1075
Give some causes of chronic liver failure.
- Alcohol - Non-alcoholic steatohepatitis - Viral hepatitis (B, C) - Autoimmune - Metabolic - Vascular
1076
What investigations should be carried out in chronic liver failure?
- Viral serology - Autoantibodies - Raised immunoglobulins - Iron studies - Copper studies - a1-antitrypsin levels - Lipids, glucose - Radiological investigations (USS/CT/MRI)
1077
Give two copper studies that can be used in Wilson’s disease.
- Caeruloplasmin | - 24hr urine copper
1078
What is autoimmune hepatitis?
Lymphoplasmacytic infiltrate directed against the hepatocytes.
1079
Autoimmune hepatitis is more common in which gender?
Females
1080
Name three antibodies which are involved in autoimmune hepatitis.
- Anti-nuclear antibody (ANA) - Anti-smooth muscle antibody (ASMA) - Liver-kidney microsome
1081
How is autoimmune hepatitis diagnosed?
Liver biopsy
1082
Describe the presentation of autoimmune hepatitis.
- 40% present with acute hepatitis | - 30% have cirrhosis at presentation
1083
Describe the cells present on liver biopsy in autoimmune hepatitis.
- Lymphocytes and plasma cells within portal tracts and lobular parenchyma - Hepatocytes may form rosettes
1084
What is the consequence of damage to the hepatocytes in autoimmune hepatitis?
Apoptosis or (in severe cases) necrosis
1085
What is a consequence of chronic autoimmune hepatitis?
Fibrosis around the portal tracts and cirrhosis.
1086
What is the treatment for autoimmune hepatitis?
- Immunosuppresant therapy (steroids) | - Liver transplant
1087
What is primary biliary cholangitis?
Granulomatous lymphocytic cholangitis directed at the small intrahepatic bile ducts.
1088
Is primary biliary cholangitis more common in males or females?
Females
1089
Give six diseases associated with primary biliary cholangitis.
- Sjogrens - Thyroiditis - Scleroderma - Rheumatoid arthritis - Lung disease - Coeliac disease
1090
Which antibodies are present in primary biliary cholangitis?
Antimitochondrial antibodies
1091
Describe the pathogenesis of primary biliary cholangitis.
- Mixed inflammatory infiltrate, rich in lymphocytes - Granulomas may be present - Can result in the destruction of the bile duct branch (ductopaenia)
1092
Describe the presentation of primary biliary cholangitis.
- May be asymptomatic - Itching and/or fatigue - Dry eyes - Joint pains - Variceal bleeding - Liver failure (ascites, jaundice)
1093
What lab abnormalities might suggest primary biliary cholangitis?
Raised alkaline phosphatase and GGT
1094
What is the treatment for primary biliary cholangitis?
- Cholestyramine for cholestatic itch - Modafinil for fatigue - Ursodeoxycholic acid (synthetic bile acid)
1095
What is primary sclerosing cholangitis?
Periductal ‘onion skin’ fibrosis directed at the large ducts, causing biliary strictures and dilatation, and potentially gallstones.
1096
Is primary sclerosing cholangitis more common in men or women?
Men
1097
Name a disease which is strongly associated with primary sclerosing cholangitis.
Inflammatory bowel disease
1098
Describe the presentation of primary sclerosing cholangitis.
- Itching - Pain +/- rigors - Jaundice
1099
Give four findings on the liver biopsy in primary sclerosing cholangitis.
- Periductal oedema (onion-ring appearance) - Lymphocytes - Potentially secondary cholangitis with neutrophils - Scarring and damage lead to ductopaenia
1100
What will the blood test results be in primary sclerosing cholangitis?
Raised alkaline phosphatase and GGT
1101
Give three complications of primary sclerosing cholangitis.
- Biliary strictures - Gallstones - Cholangiocarcinoma (10%)
1102
What is the treatment for primary sclerosing cholangitis?
- Ursodeoxycholic acid has questionable benefits | - Good results from liver transplantation
1103
Which immunoglobulin (IgG/IgM) will be raised in autoimmune hepatitis?
IgG
1104
Which immunoglobulin (IgG/IgM) will be raised in primary biliary cholangitis?
IgM
1105
Briefly describe the pathophysiology of haemochromatosis.
Autosomal recessive gene with incomplete penetrance causes uncontrolled intestinal absorption of iron with deposition in the liver, heart, and pancreas.
1106
Name two mutations associated with hereditary haemochromatosis.
- C282Y | - H63D
1107
Give four liver biopsy findings in hereditary haemochromatosis.
- Cirrhosis - Ductular proliferation at edges of fibrous septa - Minimal chronic inflammation - Blue-staining iron with Perl’s stain
1108
Give two serum measurements which are suggestive of hereditary haemochromatosis.
- Raised ferritin | - Transferrin saturation
1109
How is a diagnosis of hereditary haemochromatosis confirmed?
- HFE genotyping | - Liver biopsy (in rare cases)
1110
Give four causes of excess iron in the blood.
- Hereditary haemochromatosis - Multiple blood transfusions - Haemolysis - Alcoholic liver disease
1111
What is the treatment for hereditary haemochromatosis?
Venesection
1112
What is the expected outcome of venesection in haemochromatosis?
Iron removal may lead to regression of fibrosis.
1113
Briefly describe the pathogenesis of a1-antitrypsin deficiency.
a1-antitrypsin is a serine protease inhibitor which protects against damage from neutrophil elastase. Deficiency = damage.
1114
What condition does a1-antitrypsin deficiency cause in the liver and why?
Liver disease due to increased protein in the liver.
1115
What condition does a1-antitrypsin deficiency cause in the lungs and why?
Emphysema due to protein deficiency in the blood.
1116
Give two things that will be seen on a liver biopsy in a1-antitrypsin deficiency.
- Chronic inflammation | - a1-antitrypsin protein globules (eosinophilic with H&E, bright pink with periodic acid schiff)
1117
Describe the presentation of a1-antitrypsin deficiency in neonates and adults.
- Jaundice in neonates | - Chronic liver disease in adults
1118
What is the treatment for a1-antitrypsin deficiency?
There is no medical treatment
1119
What is Wilson’s disease?
Rare inherited disorder of biliary copper excretion, causing too much copper in the liver and CNS.
1120
Describe the genetics associated with Wilson’s disease.
Autosomal recessive disorder due to a mutation in a gene on chromosome 13 which codes for a copper transporting ATPase.
1121
What usually happens to ingested copper in the liver?
It’s absorbed from the intestine and transported to the liver, where it is incorporated in caeruloplasmin, and excreted in bile.
1122
Why does copper build up in the liver in Wilson’s disease?
The incorporation of copper into caeuloplasmin is impaired so it is not excreted in bile.
1123
How do children with Wilson’s disease usually present?
- Hepatitis - Cirrhosis - Fulminant liver failure
1124
How do young adults with Wilson’s disease usually present?
CNS signs: - tremor - dysarthria - dysphagia - dyskinesias - dystonias - purposeless stereotyped movements - dementia - parkinsonism - micrographia - ataxia/clumsiness
1125
Give two general neurological signs of Wilson’s disease.
- Mood changes | - Cognition changes
1126
What are Kayser-Fleischer rings?
Rings of copper in the iris which are present in Wilson’s disease.
1127
What investigations (and results) should be carried out in Wilson’s disease?
- Urine copper - LFTs (increased) - Serum copper - Serum caeruloplasmin (decreased) - Molecular genetic testing - Liver biopsy - MRI
1128
What is the treatment for Wilson’s disease?
- Avoid foods with high copper content - Lifelong penicillamine - Consider liver transplant - Screen siblings
1129
Which foods, that are high in copper, should people with Wilson’s disease avoid?
- Liver - Chocolate - Nuts - Mushrooms - Legumes - Shellfish
1130
Why can cirrhosis lead to hepatocellular carcinoma?
Regenerating hepatocytes have more opportunities to undergo mutations and therefore become neoplastic.
1131
Which substance do about 50% of hepatocellular carcinomas produce?
.a-fetoprotein
1132
Immunohistochemisty for which three cytokeratins can distinguish hepatocellualr carcinoma?
- 8/18 - HePar1 - CD10
1133
Give two liver conditions in which the risk of hepatocellular carcinoma is high.
- Hepatitis B/C | - Haemochromatosis
1134
Give two liver conditions in which the risk for hepatocellular carcinoma is low.
- Alcoholic liver disease | - Autoimmune diseases
1135
Is hepatocellular carcinoma more common in males or females?
Males
1136
Give an example of how a fungus can cause hepatocellular carcinoma.
Aflatoxins produced by Aspergillus are potent carcinogens for the liver.
1137
Describe the presentations of hepatocellular carcinoma.
- Decompensation of liver disease - Weight loss - Ascites - Abdominal pain
1138
Describe the treatment for hepatocellular carcinoma.
- Transplantation - Resection or local ablative therapies - Sorafenib recently shown to prolong life
1139
Describe the histology of non-alcoholic fatty liver disease.
- Hepatocytes are distended by fat - Most drugs/toxins lead to fat deposition in zone 3, but when severe whole acinus may be affected - Scattering of chronic inflammatory cells - Features identical to acute alcoholic hepatitis
1140
What is the difference between non-alcoholic fatty liver disease and non-alcoholic steatohepatitis?
Fibrosis is present in non-alcoholic steatohepatitis.
1141
Give three risk factors for non-alcoholic fatty liver disease.
- Obesity - Diabetes - Hyperlipidaemia
1142
What are the symptoms of non-alcoholic fatty liver disease?
- Usually no symptoms | - Liver ache in 10%
1143
What do the investigations show in non-alcoholic fatty liver disease?
Mildly elevated LFTs (usually ALT)
1144
What is the treatment for non-alcoholic fatty liver disease?
- No effective drug treatments | - Weight loss most effective
1145
Define acute hepatitis.
Inflammation of the liver lasting up to six months.
1146
Define chronic hepatitis.
Inflammation of the liver lasting more than six months.
1147
What are the signs/symptoms of acute hepatitis?
- Can be asymptomatic - General malaise - Myalgia - Gastrointestinal upset - Abdominal pain - May have jaundice - Tender hepatomegaly - Raised LFTs
1148
Give 6 infective causes of acute hepatitis.
- Hepatitis virus - Herpes virus - Spirochaetes (leptospirosis) - Mycobacteria (TB) - Parasites (toxoplasma) - Bacteria (coxiella)
1149
Give seven non-infectious causes of acute hepatitis.
- Alcohol - NAFLD - Drugs - Toxins/poisoning - Pregnancy - Autoimmune - Hereditary metabolic
1150
Give the signs/symptoms of chronic hepatitis.
- Can be asymptomatic/non-specific symptoms - May have signs of chronic liver disease - LFTs can be normal - If compensated, liver function is maintained - If decompensated, jaundice, ascites, low albumin, coagulopathy, encephalopathy
1151
Give two complications of chronic hepatitis.
- Hepatocellular carcinoma | - Portal hyeprtension
1152
What are the infectious causes of chronic hepatitis?
Hepatitis B+/-D, C, E
1153
Give six non-infectious causes of chronic hepatitis.
- NAFLD - Alcohol - Drugs - Toxins - Autoimmune - Hereditary metabolic
1154
How is hepatitis A spread?
Faeco-oral transmisson (person-to-person contact, contaminated food/water)
1155
Give three risk factors for hepatitis A.
- Travel - Household or sexual contact - Injecting drug use
1156
What is the mean incubation period for hepatitis A?
28 days
1157
What are the two phases of a hepatitis A infection?
Pre-icteric phase | Icteric phase
1158
What are the features of the pre-icteric phase in hepatitis A?
Constitutional symptoms and abdominal pain
1159
How long after the pre-icteric phase does the icteric phase of hepatitis A occur?
A few days to a week
1160
Describe the immunity after a hepatitis A infection.
100% immunity after infection
1161
Describe the time course of hepatitis A.
It is self-limiting (no chronic disease). | Acute liver failure in 0.35%.
1162
Describe the management for hepatitis A.
- Supportive - Monitor liver function - Management of close contacts
1163
What is the primary prevention for hepatitis A?
Vaccination
1164
Describe the epidemiology and mode of transmission in Hepatitis E (GT1).
- Africa and Asia | - Contaminated food and water
1165
Is hepatitis E (GT1) acute or chronic?
Acute
1166
Describe the epidemiology and mode of transmission of hepatitis E (GT2).
- Mexico and West Africa | - Contaminated food and water
1167
Is hepatitis E (GT2) acute or chronic?
Acute
1168
Describe the epidemiology and mode of transmission of hepatitis E (GT3).
- Worldwide (high income countries) | - Pigs and undercooked meat products
1169
Describe the epidemiology and mode of transmission of hepatitis E (GT4).
- China and South East Asia | - Pigs and undercooked meat products
1170
Describe the presentation of hepatitis E.
>95% asymptomatic | - May be extrahepatic manifestations (eg. Neurological)
1171
When might hepatitis E become chronic?
GT3 and GT4 in immunocompromised patients
1172
Which genotypes of hepatitis E have major risks in pregnancy?
GT1 and GT2
1173
Describe the management of acute hepatitis E.
- Supportive | - In fulminant hepatitis or acute-on-chronic liver failure, liaise with transplant centre and consider ribavirin
1174
Describe the management of a chronic hepatitis E infection in immunosuppressed patients.
- Reverse immunosuppression (if possible) | - If HEV RNA persists, treat with ribavirin
1175
How long is the incubation period in hepatitis B?
6 months
1176
Where in the world is hepatitis B found?
Worldwide
1177
Which mode of transmission does hepatitis B use?
Blood-borne
1178
Give four methods of transmission of hepatitis B.
- Mother to child - Sexual and household contacts - Iatrogenic - Injecting drug use
1179
What percentage of hepatitis B infections become chronic?
1-5%
1180
Describe the management of acute hepatitis B.
- Supportive - Monitor liver function - If fulminant liver failure (0.1-0.5%) consider oral nucleoside analogue and liaise with hepatology/liver transplant centre - Management of contacts
1181
What is the treatment for chronic hepatitis B?
- Pegylated interferon-a 2a (immunomodulatory) | - Nucleoside analogues
1182
Give four side effects of pegylated interferon-a 2a.
- Myalgia - Autoimmunity (thyroid) - Decreased RBCs and platelets - Mental health effects
1183
Why does hepatitis D only occur alongside hepatitis B?
It is a defective RNA virus which requires the hepatitis B antigen to replicate.
1184
How is hepatitis D transmitted?
Via blood and bodily fluids
1185
What is the patient at increased risk of if hepatitis D is acquired at the same time as hepatitis B?
Fulminant hepatitis
1186
How is hepatitis D treated?
Pegylated interferon-a
1187
What is the patient at risk of of hepatitis D is acquired after hepatitis B?
- Acute-on-chronic hepatitis | - Accelerated progression to fibrosis
1188
How many people with hepatitis C are undiagnosed or unaware of their infection?
50%
1189
What percentage of people with hepatitis C have a history of injecting drug use?
90%
1190
Give two risk factors for getting hepatitis C.
- Men who have sex with men | - Injecting drug use
1191
What is the preferred method of transmission for hepatitis C?
Permucosal
1192
What percentage of hepatitis C infections are chronic?
70%
1193
What does it mean if the HCV Ab is detected in serology testing?
The patient has been exposed to hepatitis C at some point.
1194
What does it mean if the patient has HCV RNA in their sample?
They have a current HCV infection
1195
Which HCV genotypes are the most common in England?
1 and 3
1196
What is the treatment for hepatitis C?
- Combination of directly acting antivirals from two or more of three drug classes - If symptoms, add ribavirin
1197
Describe the immunity gained when someone is infected with hepatitis C.
No immunity. They can be reinfected.
1198
Describe some steps for the prevention of hepatitis C.
- No vaccine - Screening of blood products - Universal precautions handling bodily fluids - Lifestyle modification (needle exchange) - Treatment and cure of transmitters
1199
Give three causes of transudate ascites.
- Budd-Chiari syndrome - Cirrhosis - Heart failure
1200
Give four causes of exudate ascites.
- Cancer - Sepsis - TB - Nephrotic syndrome
1201
Give three features that will be found on clinical examination of ascites.
- Shifting dullness on auscultation - Protruding umbilicus and veins - Tense abdomen
1202
What scan can be carried out to assess ascites?
Ultrasound
1203
Describe a complication of ascites.
Stasis of fluid can lead to bacterial overgrowth, resulting in spontaneous bacterial peritonitis.
1204
1 in how many women are diagnosed with breast cancer in their lifetime?
8
1205
What is the ten year survival rate in breast cancer?
78%
1206
Give five general risk factors for breast cancer.
- Age - Lifestyle - Oestrogen exposure - Family history - Genetics
1207
Give four lifestyle risk factors for breast cancer.
- Obesity - Alcohol - Night shift work - Physical inactivity
1208
What are two genes that are risk factors for breast cancer?
BRCA1, BRCA2
1209
What is the most common diagnosis of a breast lump in women 15-30yrs?
Fibroadenoma
1210
What is the most common diagnosis of a breast lump in women 30-45yrs?
Fibrocystic change
1211
What is the most common diagnosis of a breast lump in women 45-55yrs?
Cyst
1212
What is the most common diagnosis of a breast lump in women 55+yrs?
Cancer
1213
What is the risk of axillary node clearance in breast cancer sugery?
Lymphoedema
1214
When is axillary node clearance used for breast cancer?
If there are macrometastases.
1215
Give two surgical options for breast cancer.
- Wide local excision (lumpectomy) + radiotherapy | - Mastectomy
1216
Which surgical option gives the better survival prognosis in breast cancer?
Mastectomy and lumpectomy give equal survival.
1217
Give three conservative techniques that can be used in breast cancer surgery.
- Therapeutic mammoplasty - Shrink cancer before surgery - Local perforator flaps
1218
What percentage of breast and ovarian cancers do the BRCA genes account for?
<5%
1219
What is the percentage risk reduction if surgery is carried out in patients with BRCA mutations?
90%
1220
How is male breast cancer treated?
Mastectomy + radiotherapy
1221
By how much does Herceptin reduce risk of death from breast cancer?
1/3
1222
By how much does chemotherapy reduce risk of recurrence of breast cancer?
3-4%
1223
What is the downside effect of Herceptin?
Has negative effects on the heart.
1224
Give four side effects of radiotherapy for breast cancer.
- Fibrosis - Desquamating breast - Chronic skin changes - Rib fractures
1225
What is a potential sanctuary site for breast cancer?
Bone
1226
Give five common sites for breast cancer to metastasise to.
- Lymph nodes - Bone - Liver - Lung - Brain
1227
Give a monoclonal antibody which can be used to protect the bones in breast cancer.
Denosumab
1228
What is triple negative breast cancer?
Doesn’t have oestrogen receptors, progesterone receptors, or HER2 overexpression.
1229
Describe the current NHS breast screening programme.
- Offered to all women between the ages of 50 and 71 | - Offered every three years
1230
Give ten risk factors that may be cause for concern with women presenting with a breast lump. (Factors independent of the lump)
- Previous history of breast cancer - Family history - Older age - No children, or first child after the age of 30 - Not having breast-fed - Early menarche/late menopause - HRT - Chest radiation - Obesity - High alcohol intake
1231
Compare the consistency of a malignant and benign breast lump.
MALIGNANT - Hard consistency BENIGN - Firm/rubbery consistency
1232
Compare the pain of a malignant and benign breast lump.
MALIGNANT - 90% painless BENIGN - Often painful
1233
Compare the margins of a malignant and benign breast lump.
MALIGNANT - Irregular margins BENIGN - Regular/smooth margins
1234
Compare whether benign and malignant are fixed to the chest wall.
MALIGNANT - May be fixed BENIGN - Mobile and not fixed
1235
Describe skin dimpling of a malignant and benign breast lump.
MALIGNANT - May be skin dimpling BENIGN - Skin dimpling unlikely
1236
Describe discharge of a malignant and benign breast lump.
MALIGNANT - May be bloody, unilateral discharge BENIGN - No blood, but may have bilateral discharge
1237
Describe nipple retraction of a malignant and benign breast lump.
MALIGNANT - May have nipple retraction BENIGN - No nipple retraction
1238
Give three criteria for breast lumps to be referred urgently.
- Women of any age with discrete, hard lump with fixation, +/- skin tethering - Women >30yrs with discrete lump that persists after next period or presents after menopause - Women <30yrs who present with a lump that enlarges, that is fixed/hard, or with other reasons for concern
Phase2a
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