Haematology and Endocrinology Flashcards
What are the two main components of a full blood count and what are the names of the conditions in which they get deranged?
Hb – anaemia or polycythaemia
Platelets – thrombocytopaenia or thrombocytosis
List two causes of polycythaemia
Primary polycythaemia (polycythaemia rubra vera) Secondary polycythaemia (secondary to chronic hypoxia in COPD patients, a tumour that is producing ectopic EPO)
What are the three mechanisms of thrombocytopaenia? State a cause for each.
Reduced production of platelets (e.g. bone marrow infiltration, leukaemia, lymphoma, drugs (e.g. chemotherapy))
Destruction of platelets (e.g. consumption of platelets in DIC)
Pooling of platelets (e.g. pooling within the spleen in patients with chronic liver disease and portal hypertension)
Broadly speaking, what can cause a high WCC?
Infection
Malignancy
List two main causes of microcytic anaemia.
Iron deficiency anaemia
Beta thalassemia heterozygosity
What are the two main mechanisms of iron deficiency anaemia?
Blood loss
Dietary deficiency
List some causes of normocytic anaemia.
Anaemia of chronic disease
Infection
Malignancy
Inflammation (RhA)
Describe the ferritin level in anaemia of chronic disease.
Normal/high – because ferritin is an inflammatory marker, that is raised in inflammatory conditions (e.g. rheumatoid arthritis)
Describe the relationship between MCV and Hb in beta thalassemia heterozygosity.
The MCV is very low and out of proportion to the degree of anaemia
List 5 causes of macrocytic anaemia.
Mnemonic – alcoholics may have liver failure
Alcoholism Myelodysplasia Hypothyroidism Liver disease Folate/B12 deficiency
For each of the 5 causes, state some clinical clues that can be found on history, examination and investigation.
Alcoholism – history + raised GGT
Myelodysplasia – pancytopaenia + bone marrow biopsy
Hypothyroidism – history + TFTs (low T4 + high TSH)
Liver disease – history + exam
Folate/B12 deficiency – history (e.g. small bowel disease, ?gastrectomy)
Alcoholics May Have Liver Failure
List the main symptoms of polycythaemia.
Headache Pruritus after a hot bath Blurred vision Tinnitus Thrombosis (DVT/stroke) Gangrene Choreiform movement (dancelike)
What are the three main complications of sickle cell anaemia.
Acute painful crisis
Sequestration crisis
Gallstones/chronic cholecystitis
Describe the management of acute painful crisis.
Analgesia
Oxygen (hypoxia can cause sickling)
IV fluids (dehydration can cause sickling)
Antibiotics - if underlying infection
How is stroke treated in sickle cell patients?
Exchange blood transfusion to remove the sickled cells
Where can blood cells pool in sequestration crisis and what symptoms does this cause?
Lungs – SOB, cough, fever
Spleen – exacerbation of anaemia
How do you treat splenic sequestration crisis?
Splenectomy
Why do patients with sickle cell anaemia suffer from chronic cholecystitis?
Increased breakdown of Hb leads to increased risk of forming pigment stones
This can lead to chronic cholecystitis
How is chronic cholecystitis secondary to SCA treated?
Cholecystectomy
What are the four main features of multiple myeloma?
Calcium (high)
Renal impairment
Anaemia
Bone
For each of the four main features, list important findings on presentation/investigation.
Calcium – polyuria, polydipsia, constipation (leads to ADH resistent so Nephrogenic DI develops)
Renal impairment – high urea and creatinine
Anaemia – SOB, lethargy, FBC
Bone – fracture, pain, DEXA scan for OP
What are two other important complications of multiple myeloma?
Increased risk of infection
Cord compression
Why are multiple myeloma patients more likely to suffer from infections?
Multiple myeloma leads to increased production of one type of immunoglobulin
This leads to reduced production of other immunoglobulins (immune paresis), which increases risk of infection
What can cord compression due to multiple myeloma lead to?
Spastic paraparesis – partial paralysis of the lower limbs
Describe the ALP in multiple myeloma. Why is this the case?
ALP is normal/low in multiple myeloma
Multiple myeloma suppresses the osteoblasts, which are responsible for producing ALP
What are reticulocytes?
Immature red blood cells
List the two main causes of anaemia with HIGH reticulocytosis.
Haemorrhage
Haemolysis
NOTE: reticulocytosis occurs when there is an increased demand for red blood cells
List three causes of anaemia with LOW reticulocytes.
Parvovirus B19
Aplastic crisis in sickle cell patients
Blood transfusion
List the three main diagnostic criteria for diabetes mellitus.
Fasting blood glucose > 7 mmol/L
Random blood glucose > 11.1 mmol/L
HbA1c > 6.5% or > 48 mmol/mol
Why was the diagnostic cut-off for fasting blood glucose set at > 7 mmol/L?
Epidemiological studies showed that the rate of incidence of retinopathy significantly increased in patients with fasting blood glucose > 7 mmol/L
What is impaired glucose tolerance (IGT)?
A blood glucose of 7.8-11.1 mmol/L measured 2 hours after an oral glucose tolerance test (OGTT), in which 75 g of glucose is administered orally
Other than type 1 and type 2 diabetes mellitus, what else can cause diabetes? Why is this difficult to treat?
Pancreatic insufficiency - complete lack of enzymes - ‘Type 3’
NOTE: complete pancreatic insufficiency is difficult to treat because the lack of glucagon and pancreatic polypeptide is difficult to manage
What is the first drug that is given to patients with type 2 diabetes mellitus?
Metformin (reduces insulin resistance)
At what point do you add more medications for diabetics on metformin? What is the pathway?
If the patient fails to achieve the target HbA1c despite metformin - add Sulfonylurea or GLP1 agonist, then if still high, add DPP4 inhibitor
Eventually consider insulin
Which commonly used medication for type 2 diabetes can cause hypoglycaemia?
Sulfonylureas
If the patient is overweight or you want to avoid hypoglycaemia, which diabetic medication might you consider using?
GLP-1 agonists (incretin effect)
Mechanism of action of Metformin
Decreases insulin resistance
Mechanism of action of Sulfonylureas
Stimulates insulin release (insulin secretalogue)
Mechanism of action of DDP-IV inhibitors
Reduces GLP-1 breakdown
Mechanism of action of GLP-1 agonists
Incretin that stimulates glucose-stimulated insulin release
Also inhibits glucagon release, reduces appetite and may cause some weight loss
What is one of the first signs of diabetic nephropathy?
Increase in albumin: creatinine ratio
When might you put a patient on an insulin sliding scale? What is it?
If a diabetic patient is not eating or really unwell
(IV infusion at rate determined by blood glucose) - give basal (glargine) and bolus insulin + fluids (could include dextrose)
When are insulin sliding scales not indicated?
What medication would you initially try? Why?
Sepsis
Daily long-acting insulin is preferred
NOTE: if the patient is ill and not eating very much, the long-acting insulin along may be sufficient to meet their insulin demands at the time
What is the main difficulty with insulin sliding scales?
It requires constant monitoring of blood glucose and constant adjustment of the insulin delivery rate.
Associated with increased mortality
In what context is a sliding scale most useful?
Surgery – a patient might have to be NBM for a long time
List some symptoms of Graves’ disease.
Weight loss Increased appetite (DDx infx, inflx) Irritability Palpitations Irregular periods
Tremor
Proptosis
Smooth Goitre
Pretibial Myxoedema (skin changes) - specific
Describe the TFT results in a patient with Graves’ disease?
High T4/T3 Low TSH (<0.05)
What would a high TSH with high T4/T3 suggest?
Secondary hyperthyroidism
After performing TFTs and putting together a clinical picture of primary hyperthyroidism, what test would you do next?
TSH receptor stimulating antibodies
Other than stimulating the TSH receptors, what else do TSH receptor stimulating antibodies do?
They stimulate adipocytes and fibroblasts at the back of the eye to produce glycosaminoglycans (GAGs), which are hydrophilic and cause proptosis
They are also responsible for the skin changes in pretibial myxedema
What are TPO antibodies a marker of?
Autoimmunity
They are present in about 5% of the general population
What will radioiodine uptake scans of Graves’ disease patients show?
Diffuse increased uptake
What needs to happen for the thyroid gland to be able to take up iodine?
The TSH receptor must be stimulated for there to be iodine uptake
Describe and explain the iodine uptake in thyroiditis.
NO iodine uptake because TSH is suppressed in thyroiditis
Describe and explain the iodine uptake in toxic nodular goitre.
The scan will show a single hot nodule that is autonomous and no longer controlled by TSH
There will not be much uptake from the rest of the gland, because high T4/T3 suppresses TSH levels, which, therefore, will not stimulate iodine uptake in the rest of the thyroid gland that is functioning normally
List some risk factors for thyroid cancer.
Radiation
Family history
Rapid enlargement/compression
Lymphadenopathy
What percentage of the general population has thyroid nodules?
60-70%
Where do most thyroid cancers metastasise to? Which type of thyroid cancer has a propensity to metastasise to this location?
Lungs
These tend to be mostly follicular thyroid cancer
List two investigations that may be used in the diagnosis of thyroid cancer.
Ultrasound scan
Fine needle aspiration cytology
Uptake scan (thyroid cancers are cold)
List four types of thyroid cancer.
Papillary
Follicular
Medullary (FHx)
Anaplastic
Which type of thyroid cancer has the worst prognosis?
Anaplastic
List two treatments that are used after surgery in patients with thyroid cancer.
Thyroxine – replace the function of the lost thyroid gland
Radioiodine – in high-risk patients
List the signs of a prolactinoma.
Amenorrhoea
Galactorrhoea
Bitemporal hemianopia
Sexual dysfunction, irregular periods
Which type of prolactinoma can compress the pituitary stalk?
Macroprolactinoma
What is the first-line treatment for prolactinoma?
Dopamine agonists (e.g. cabergoline, bromocriptine)Shrinks and normalises PRL
(TransSph if not responsive)
Roughly how long are prolactinoma patients kept on this treatment?
4 years – then they can gradually be weaned off and some may be able to stop it entirely
Describe the symptoms of acromegaly.
Headaches
Sweating
Obstructive sleep apnoea (poor sleep, snoring)
Carpal tunnel syndrome (tingling fingers)
What causes obstructive sleep apnoea?
Excessive soft tissue obstructing the upper airways during sleep
What is the first test you do in the investigation of acromegaly?
IGF-1 levels
What is the next test you do to diagnose acromegaly?
Oral Glucose Tolerance Test Failure of suppression of GH after oral intake of glucose suggests acromegaly NOT GHRH (distractor)
How do you test pituitary function?
- Insulin tolerance test
Insulin causes hypoglycaemia, which should lead to an increase in the production of GH - Dynamic pituitary function test (check pit. status post surgery)
What is a dexamethasone suppression test used for?
Test for Cushing’s syndrome
In normal people, dexamethasone will suppress ACTH and hence suppress cortisol
In people with Cushing’s syndrome, the cortisol level will remain high
What is a short synacthen test used for?
Test for adrenal insufficiency
In normal people, synacthen will stimulate the adrenals to produce cortisol so cortisol levels will rise considerably following the administration of cortisol
In people with adrenal insufficiency, cortisol levels will not rise considerably after the administration of synacthen
What are the three distinguishing symptoms of Cushing’s syndrome?
Proximal myopathy
Easy bruising, thin skin
Purple Striae > 1 cm wide
List some disease states that are caused by Cushing’s syndrome.
Hypertension
Diabetes mellitus
Osteoporosis
(at young age)
What are striae?
Capillaries that become visible due to stretching and thinning of the skin
Broadly speaking, how can the causes of amenorrhoea/oligomenorrhoea be divided?
Pregnancy Hypothalamus Pituitary Thyroid Ovaries
List two hypothalamic causes of amenorrhoea.
Excessive exercise (less oestrogen --> OP) Low BMI
Why does low BMI lead to amenorrhoea?
Low BMI will mean that leptin levels are low
Leptin has a permissive effect over the hypothalamo-pitutiary-gonadal axis –> less leptin = less GnRH
What is the main pituitary cause of amenorrhoea?
Prolactinoma
What derangements of thyroid function can cause amenorrhoea?
Hypothyroidism
Hyperthyroidism
List two ovarian causes of amenorrhoea.
PCOS -> excess androgens
Ovarian failure -> low oestradiol + high FSH/LH
What are the three main signs of hypokalaemia?
Weakness
Arrhythmia
Polyuria
List the three main causes of hypokalaemia.
Vomiting
Diuretics
Primary hyperaldosteronism
Describe how hypokalaemia leads to polyuria.
Hypokalaemia causes ADH resistance –> nephrogenic diabetes insipidus, which leads to polyuria
Similar to hypercalcaemia
List two examples of primary hyperaldosteronism.
Conn’s syndrome
Bilateral adrenal hyperplasia
What can be measured to assist with a diagnosis of primary hyperaldosteronism?
Aldosterone: renin ratio
Why is hypernatraemia very rare?
Normally, if our serum Na+ is high, we would drink some water to dilute it
List two conditions that can cause hypernatraemia.
Diabetes insipidus
Dementia (forgetting to drink water)
State the formula for calculation of urine osmolality.
Osmolality = 2(Na+ + K+) + Ur + glucose
List causes for hypernatraemia with high urine osmolality
Dehydration
Hyperosmolar hyperglycaemic state (HHS)
NOTE: urine osmolality is high in HHS because of glycosuria
List a cause for hypernatraemia with low urine osmolality
Diabetes insipidus
Lack of ADH –> less water absorption –> water loss in urine
Describe the actions of PTH.
Increase resorption of calcium in the bones
Increased reabsorption of calcium in the kidneys
Increased excretion of phosphate in the kidneys
Describe biochemical features of primary hyperparathyroidism.
High Ca2+
Low phosphate
Describe the calcium, phosphate and PTH levels in hypercalcaemia of malignancy.
High Ca2+
Normal phosphate
Low PTH
Name the two hormones that control serum calcium concentration.
PTH
Calcitriol (Vitamin D)
Describe the biochemical features of hypoparathyroidism.
Low Ca2+
High phosphate
Low PTH
Describe the biochemical features of renal failure.
Low Ca2+
High phosphate
High PTH
Explain the biochemical features of renal failure.
The kidneys are not able to reabsorb calcium and they are not able to activate vitamin D leading to hypocalcaemia
The kidneys are also unable to excrete phosphate leading to hyperphosphataemia
The hypocalcaemia leads to a secondary hyperparathyroidism
Describe the biochemical features of vitamin D deficiency.
Low Ca2+
Low phosphate
High PTH
List causes for each of the following types of AKI:
Pre-renal: hypovolaemia, sepsis, heart failure
Intrinsic renal: drugs, glomerulonephritis
Post-renal: obstruction (e.g. stones) - nephrostomy to relieve obstruction
What can be found in the urine of a patient with glomerulonephritis?
Active urine sediment: blood and protein
Which investigation does every AKI patient need?
Ultrasound scan – check for signs of obstruction
What anatomical deformity does renal artery stenosis lead to?
Asymmetrical kidneys
How is renal artery stenosis investigated?
Magnetic resonance angiography (MRA)
Which drug class is contraindicated in bilateral renal artery stenosis and why?
ACE inhibitors
It can cause a massive drop in GFR
Why does hyperventilation cause tingling in the hands?
Hyperventilation leads to hypocalcaemia, which causes neuromuscular excitation -> tingling
Describe the pattern of arthritis in rheumatoid arthritis.
Symmetrical polyarthritis
List the five types of psoriatic arthritis.
- Asymmetrical oligoarthritis (more common and affects distal joints)
- Symmetrical polyarthritis (look like rheumatoid arthritis)
- Large joints (e.g. swollen knee)
- Arthritis mutilans (telescoping of the fingers)
- Psoriatic spondyloarthritis (axial skeleton involvement e.g. sacroiliitis)
Describe the appearance of a BCC.
Pearl-like lesion with a rolled edge and telangiectasia
Complications of diabetes
Microvascular - Retinopathy, Nephropathy, Neuropathy
Macrovascular: MI/Stroke/PVD
Metabolic: DKA/HHS/Hypoglycaemia
Explain Retinopathy and Nephropathy
Retinopathy - Backgroud, pre-proliferative (soft exudates/cotton wool spots), proliferative
Nephropathy: raised urine ACR (albumin:creatinine ration), decreased renal function
(Send dip to lab to detect microalbuminuria, cannot get ratio from urinalysis)
What should you note in Grave’s?
TPO Ab is a marker of AI (5% of normal population), not cause of disease; so do not need to check
Psoriatic Arthritis Symptoms
Swollen fingers and toes Tender, painful or swollen joints Red Scaly Skin patches known as Plaques Reduced Range of motion of the joints Morning stiffness Lower back, upper back and neck pain General fatigue Nail changes
