GP

Question 1

Most frequent causes of megaloblastic anaemia?

Answer 1

Vitamin B12 or Folate deficiency

Question 2

Anaemia normal ranges according to population

Answer 2

In children aged 12–14 years — Hb concentration less than 120 g/L.
In men (aged over 15 years) — Hb concentration less than 130 g/L.
In women (aged over 15 years) — Hb concentration less than 120 g/L.
In 1st trimester - Hb concentration less than 110 g/L
In the 2nd and 3rd trimester - Hb concentration less than 105 g/L
Postpartum — Hb concentration less than 100 g/L.

Question 3

How does absorption of vitamin B12 take place?

Answer 3

Vitamin B12 combines with intrinsic factor (IF), which is produced by parietal cells in the stomach, to form an IF–B12 complex. The complex binds to surface receptors for IF in the distal ileum, which then allows absorption of vitamin B12 to take place.

Question 4

How long can body stores of Vit B12 last?

Answer 4

2-5 yrs

Question 5

Most common cause of severe B12 deficiency?

Answer 5

pernicious anaemia

Question 6

Some other causes of B12 deficiency?

Answer 6

Drugs — colchicine, metformin, nitrous oxide, protein pump inhibitors, H2-receptor antagonists. (NOMPCH)
Gastric — total or partial gastrectomy, congenital intrinsic factor deficiency or abnormality, Zollinger-Ellison syndrome.
Inherited causes.
Intestinal — malabsorption (for example gluten-induced enteropathy), ileal resection, Crohn’s disease, blind loop syndrome, parasites (for example, giardiasis, fish tapeworm).
Nutritional — malnutrition, vegan diet.

Question 7

What antibodies are related to pernicious anaemia and how?

Answer 7

Antibodies to IF are very specific for pernicious anaemia, however they are only present in around 50% of people.
Anti-parietal cell antibodies occur in 90% of people with pernicious anaemia, however they are less specific and common in older people who do not have pernicious anaemia.

Question 8

Epidemiology of pernicious anaemia

Answer 8

Pernicious anaemia affects more women than men. Adult pernicious anaemia (the most common cause of B12 deficiency and megaloblastic anaemia) occurs most commonly in people aged 40–70 years, with a mean age of onset of 60 years among white people.
In black people the mean age is 50 years, with a biomodal distribution due to an increased occurence in young black females.

Question 9

Complications of pernicious anaemia

Answer 9

increased risk of developing gastric cancer (2–3% of all cases of pernicious anaemia)
an association with other autoimmune diseases (including myxoedema, thyrotoxicosis, Hashimoto’s disease, Addison’s disease, and vitiligo).

Question 10

Where is Folate absorbed?

Answer 10

Folate is usually absorbed through the upper part of the small intestine (Duodenum and Jejunum) and body stores are sufficient for around 4 months.

Question 11

Causes of Folate deficiency

Answer 11

reduced dietary intake
Drugs — alcohol, anticonvulsants, nitrofurantoin, sulfasalazine, methotrexate, trimethoprim. (TANSAM)
Increased requirements, for example, due to:
Pregnancy and lactation, prematurity.
Malignancy (for example leukaemia, carcinoma, or
lymphoma).
Blood disorders (for example haemolytic anaemias,
sickle cell anaemia, myelofibrosis).
Inflammatory diseases (for example tuberculosis,
Crohn’s disease, or malaria).
Exfoliative skin diseases.
Excessive urinary excretion (for example due to congestive heart failure, acute liver damage, or chronic dialysis).
Liver disease.
Malabsorption — due to coeliac disease, tropical sprue, congenital specific malabsorption, jejunal resection, or inflammatory bowel disease.
Nutrition — alcoholism or dietary fads.

Question 12

Complications of anaemia

Answer 12

Adults (especially the elderly) with severe anaemia are at risk of cardiopulmonary complications, such as heart failure.

Question 13

Complications of vitamin B12 deficiency

Answer 13

Neurological symptoms — for example, paraesthesia, ataxia, progressive symmetrical neuropathy which affects the legs more than the arms, numbness, poor motor coordination, memory lapses, and age-related cognitive impairment. Optic atrophy and severe psychiatric symptoms occur rarely.
Note: neurological disorders can occur independently of the haematological manifestations of pernicious anaemia.
deficiency in women who are pregnant predisposes to neural tube defects (such as spina bifida, anencephaly, and encephalocele) in the foetus.
may cause ineffective production of any types of blood cells derived from bone marrow.
May cause sterility. This is reversible with appropriate vitamin supplementation.

Question 14

Complications of folate deficiency

Answer 14

Maternal folate deficiency in pregnancy is associated with prematurity.
it may be associated with cardiovascular disease and some cancers.
deficiency in women who are pregnant predisposes to neural tube defects (such as spina bifida, anencephaly, and encephalocele) in the foetus.
may cause ineffective production of any types of blood cells derived from bone marrow.
May cause sterility. This is reversible with appropriate vitamin supplementation.

Question 15

Nature of onset of megaloblastic anaemia? sudden or insidious?

Answer 15

onset of megaloblastic anaemia is usually insidious, with gradually progressive signs and symptoms.

Anaemia due to pernicious anaemia may develop gradually over several years, and symptoms may not appear until it is severe.

Note: clinical features of vitamin B12 deficiency can occur without anaemia and without low serum levels of vitamin B12.

Question 16

5 Symptoms of vitamin B12 and folate deficiency

Answer 16

Cognitive changes. 
Dyspnoea. 
Headache.
Indigestion.
Loss of appetite.
Palpitations.
Tachypnoea.
Visual disturbance. 
Weakness, lethargy. 
(People with pernicious anaemia may present with symptoms of associated disorders, for example, myxoedema, other thyroid disorders, vitiligo, stomach cancer, or Addison's disease.)

Question 17

5 Signs of vitamin B12 and folate deficiency

Answer 17

Anorexia.
Angina (in older people).
Angular cheilosis.
Brown pigmentation affecting nail beds and skin creases (but not mucous membranes).
Congestive heart failure (in older people).
Episodic diarrhoea.
Glossitis — red smooth and shiny tongue, perhaps with ulcers.
Heart murmurs.
Liver enlargement.
Mild jaundice — a lemon-yellow tint.
Mild pyrexia.
Oropharyngeal ulceration.
Pallor of mucous membranes or nail beds.
Tachycardia.
Weight loss.

Question 18

5 Neurological complications associated with vitamin B12 deficiency

Answer 18

Loss of cutaneous sensation.
Loss of mental and physical drive.
Muscle weakness.
Optic neuropathy.
Psychiatric disturbances – these range from mild neurosis to severe dementia.
Symmetrical neuropathy affecting the legs more than the arms — this usually presents with ataxia or paraesthesia.
Urinary or faecal incontinence.

Question 19

What investigations would you arrange for people with suspected vitamin B12 or folate deficiency?

Answer 19

FBC, blood film, serum cobalamin and folate levels. Additional investigations, such as liver function tests, gamma-glutamyl transpeptidase, and/or thyroid function tests — to identify the underlying cause.

If there is a strong clinical suspicion of folate deficiency but normal serum levels, red cell folate can be measured once cobalamin deficiency has been ruled out.

Question 20

main cause of folate malabsorption?

Answer 20

gluten-induced enteropathy

Question 21

State 5 differentials for macrocytosis

Answer 21

Vitamin B12 and folate deficiencies (megaloblastic cause)

Other (non-megaloblastic) causes of macrocytosis include:

• Alcohol — may cause macrocytosis with neither anaemia nor a change in liver function. ( most frequent cause of a raised mean cell volume (MCV) in the absence of anaemia.)
• Drugs — antimetabolites, such as hydroxycarbamide, methotrexate and azathioprine.
• Haematological abnormalities such as Myelodysplasia, Aplastic anaemia, etc.
• Liver disease — chronic liver disease is associated with anaemia that is mildly macrocytic.
• Pregnancy and the neonatal period.
• Severe thyroid deficiency
• Smoking.

Question 22

What is the management for vitamin B12 deficiency?

Answer 22

For people with neurological involvement:
Seek urgent specialist advice from a haematologist.
For people with no neurological involvement:
Initial treatment: IM hydroxocobalamin 1 mg three times a week for 2 weeks.
Maintenance treatment:
B12 deficiency that is not thought to be diet related — administer hydroxocobalamin 1 mg intramuscularly every 2–3 months for life.
Thought to be diet related — advise people either to take oral cyanocobalamin tablets 50–150 micrograms daily between meals, or have a twice-yearly hydroxocobalamin 1 mg injection. (In vegans, treatment may need to be life-long)
Give dietary advice about foods that are a good source of vitamin B12 - Eggs, Foods which have been fortified with vitamin B12 (for example some soy products, and some breakfast cereals and breads), Meat, Milk and other dairy products, Salmon and cod.

Caution: cyanocobalamin should not be used to treat megaloblastic anaemia in pregnancy, as this is caused by folic acid deficiency.

Question 23

What is the management for Folate deficiency?

Answer 23

Prescribe oral folic acid 5 mg daily — in most people, treatment will be required for 4 months.
Check vitamin B12 levels in all people before starting folic acid — treatment can improve wellbeing, mask underlying B12 deficiency, and allow neurological disease to develop.
Give dietary advice about foods that are a good source of folic acid —:
Asparagus.
Broccoli.
Brown rice.
Brussels sprouts.
Chickpeas.
Peas.

Question 24

Monitoring requirements after treatment for vitamin B12 or folate deficiency has started?

Answer 24

FBC and reticulocyte count within 7–10 days of starting treatment.
FBC, reticulocyte count, iron and folate levels after 8 weeks of treatment
FBC and reticulocyte count on completion of folate treatment
Cobalamin can be measured 1–2 months after starting treatment if there is no response.

Neurological recovery may take some time — improvement begins within one week and complete resolution usually occurs between six weeks and three months.

Question 25

Cluster headache presentation

Answer 25

Cluster headache is a rare but severe headache disorder characterized by:
-Unilateral periorbital pain.
-Ipsilateral autonomic symptoms such as conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhoea, eyelid oedema, forehead and facial sweating or flushing.
-Brief attacks of less than 3 hours duration.
- the person may identify a trigger for the attacks
it is the most common trigeminal autonomic cephalalgia. The name relates to the pattern of the headaches - they typically occur in clusters lasting several weeks, with the clusters themselves typically once a year.

Question 26

associations and risk factors for cluster headaches

Answer 26

Cluster headaches are more common in men (4:1) and smokers. Alcohol intake is also associated

Question 27

complications of cluster headaches and prognosis

Answer 27

restriction of daily activities during attacks.
can evolve from intermittent to chronic

• cluster headache is thought to be a lifelong disorder periods of remission may lengthen with increasing age

Question 28

Diagnostic criteria for cluster headache

Answer 28

• At least five attacks of severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes and
  
  • Headache associated with at least one of: ipsilateral conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhoea; eyelid oedema; forehead and facial sweating or flushing; a sensation of fullness in the ear; or miosis and/or ptosis; and/or a sense of restlessness or agitation.
  • Attacks occur between one every other day and eight per day for more than half of the time when the disorder is active.
  • The headache is not better accounted for by another ICHD-3 ( International Classification of Headache Disorders) diagnosis.

Question 29

ddx for cluster headaches

Answer 29

• migraine
• tension type headache
• other trigemical autonomic cephalgias
• Trauma or injury to the head and/or neck.
• Cranial or cervical vascular disorders for example intracerebral haemorrhage, central venous thrombosis or giant cell arteritis.
• Non-vascular intracranial disorders for example idiopathic intracranial hypertension or neoplasm.
• Exposure to, or withdrawal from, a substance such as carbon monoxide, cocaine or alcohol or medication overuse headache
• Infection for example intracranial infection or systemic infection.
  - Disorders of homeostasis for example hypoxia or hypertension including pre-eclampsia and eclampsia.
  - Disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cranial structure such as angle closure glaucoma, temporomandibular disorder, dental problems, otitis media or sinusitis.
• Psychiatric disorders such as somatization disorder.
• Painful cranial neuropathies and other facial pains such as trigeminal neuralgia, post-herpetic neuralgia and optic neuritis.

Question 30

management of cluster headaches

Answer 30

If clinical features are consistent with cluster headache refer to/discuss with a neurologist or GP with a special interest in headache

acute attacks - S/C sumitriptan or intranasal sumitriptan or zolmitriptan. If not contra-indicated, provide 100% oxygen at a flow rate of 12–15 litres per minute via a non-rebreather face mask for 15 to 20 minutes.
advice avoiding triggers, using headache diaries, patient information leaflets/websites.

prophylaxis: verapamil is the drug of choice.

Question 31

How can toxoplasmosis present in an immunocompetent patient? How would you investigate for it? Is treatment required?

Answer 31

Most infections are asymptomatic. Symptomatic patients usually have a self-limiting infection, often having clinical features resembling infectious mononucleosis (fever, malaise, lymphadenopathy). Other less common manifestations include meningoencephalitis and myocarditis.

Serology is the investigation of choice.

No treatment is usually required unless the patient has a severe infection or is immunosuppressed.

Question 32

How does cerebral toxoplasmosis present? epidimiology? management?

Answer 32

cerebral toxoplasmosis presents with constitutional symptoms, headache, confusion, drowsiness. Immunosuppressed patients may also develop a chorioretinitis secondary to toxoplasmosis.
CT: usually single or multiple ring-enhancing lesions, mass effect may be seen
Cerebral toxoplasmosis accounts for around 50% of cerebral lesions in patients with HIV and affects immunosuppressed patients as well.
management: pyrimethamine plus sulphadiazine for at least 6 weeks

Question 33

acute itch definition

Answer 33

when symptoms last for less than 6 weeks

Question 34

causes of widespread itch that is not associated with a rash or a skin disorder?

Answer 34

idiopathic
dry skin (xerosis) - most common in elderly
infection and infestation (scabies, parasite, hep B and hep C)
systemic disease including:
- renal disease (due to uraemia)
- liver disease
- haematological (eg iron deficiency anaemia, polycythaemia, etc.)
- Endocrine disorders — such as diabetes mellitus, thyroid disorders, and primary hyperparathyroidism (rare)
- Malignancy — for example Hodgkin’s lymphoma, cutaneous T-cell lymphoma, leukaemia, and multiple myeloma
- Neurological — for example due to spinal cord tumours or multiple sclerosis
- menopause
- Drugs - opioids, statins, ACEIs, digoxin, thiazide diuretics, CCBs, topiramate, chloroquine and sulphonamides. also cancer treatments
- psychogenic

Question 35

complications of Widespread itch?

Answer 35

• disturbed sleep
• anxiety and depression
• social isolation, embarrassment, stigmatisation, negative body image due to uncontrolled scratching and visible skin lesions.
• Impaired memory and concentration.
• Secondary scratch lesions, such as excoriations, lichenification, skin nodules, lichen simplex chronicus, atrophic scarring, and hypo- or hyperpigmentation due to persistent scratching.
• Secondary bacterial infection of excoriations such as impetigo.

Question 36

what are the management options for symptomatic relief of itch?

Answer 36

• self care advice
  in steps -
  1.emollient
  2. trial of an emollient with an active ingredient (such as menthol 0.5% or 1% in aqueous cream)
  3.short-term trial of a non-sedating oral antihistamine, such as cetirizine or loratadine.
  //troublesome nocturnal itch, consider a short-term trial of a sedating oral antihistamine, such as hydroxyzine or chlorphenamine at night
  4. arrange referral or seek specialist advice

Question 37

self-care advice if a person has widespread itch of known or unknown cause

Answer 37

avoid excessive showering or bathing
Keep nails short to minimize skin damage
Keep the indoor environment cool and consider humidifying the air, particularly during cold winter months.
Wear loose clothing that does not irritate the skin (for example cotton or silk). Avoid wool or synthetic fabrics.
Avoid spicy foods, alcohol, and caffeine as they may worsen symptoms
refer to leaflets and online websites

Question 38

BMI for healthy weight

Answer 38

18.5–24.9 kg/m2

Question 39

Overweight BMI

Answer 39

25–29.9 kg/m2

Question 40

Obesity l BMI

Answer 40

30–34.9 kg/m2

Question 41

Obesity ll BMI

Answer 41

35–39.9 kg/m2

Question 42

Obesity lll BMI

Answer 42

40 kg/m2 or more

Question 43

Factors which contribute to overweight and obesity?

Answer 43

Lifestyle factors
Genetics
Medical conditions
Medications
Age
Peri-and menopause
sleep deprivation
less formal education
low socioeconomic status

Question 44

Lifestyle factors which contribute to overweight and obesity?

Answer 44

diet high in sugar and fat, eating out, larger portions, more than 2 drinks per day
Physical inactivity (inactive = doing less than 30 minutes of physical activity a week)
Social and psychological factors like comfort eating in relation to low self esteem

Question 45

Medical conditions which contribute to overweight and obesity?

Answer 45

Cushing’s syndrome
Growth hormone deficiency
Hypothyroidism
Hypothalamic damage (for example due to a tumour, trauma, or surgery).
Genetic syndromes associated with hypogonadism (for example Prader-Willi syndrome
PCOS

Question 46

Medications which contribute to overweight and obesity

Answer 46

Pizotifen
Beta blockers
corticosteroids
lithium
antipsychotics - especially atypical antipsychotics
anticonvulsants - sodium valproate, gabapentin, vigabatrin
Antidepressants — tricyclics, mirtazapine, monoamine oxidase inhibitors (MAOIs).
Insulin — when used in the treatment of type 2 diabetes.
Oral hypoglycaemic drugs — sulphonylureas, thiazolidinediones (glitazones)

Question 47

What are the complications of overweight and obesity?

Answer 47

increased risk of developing:
-     Type 2 diabetes.
-    Coronary heart disease.
-    Hypertension and stroke.
-    Asthma.
-    Depression.
-    Metabolic syndrome.
-    Dyslipidaemia.
-    Cancer.
-    Gastro-oesophageal reflux disease (GORD).
-    Gallbladder disease.
-    Reproductive problems.
-    Osteoarthritis and back pain.
-    Obstructive sleep apnoea.
-    Breathlessness.
-    Psychological distress. 
Decreased life expectancy
obesity contributes to reinforcing existing social inequalities
obese people have poorer job prospects, are less likely to be employed, have more difficulty re-entering the labour market, and are less productive at work due to more sick days and fewer worked hours. They also earn about 10% less than their non-obese colleagues

**Most of the complications of obesity can be reduced by weight loss!!! a 10 kg weight loss can have significant benefits and effects on prognosis!

Question 48

Management of obesity

Answer 48

Encourage the person’s partner or spouse to support any weight management programme
assess for:
- willingness and motivation to lose weight.
- feelings about being overweight (for example beliefs and previous attempts to lose weight) and their confidence in making changes.
- underlying causes and comorbidities
- risk of developing complications of obesity.
Multicomponent interventions are the treatment of choice. this can includes assessing for causes, lifestyle management, medications and bariatric surgery.