3. Core Clinical Biochemistry Flashcards
Secrete hormones directly into the blood stream and act systematically.
- Autocrine secretion
- Paracrine system
- Endocrine glands
- Thyroid glands
- Endocrine glands
Secrete hormones that act locally.
- Autocrine secretion
- Paracrine system
- Endocrine glands
- Thyroid glands
- Paracrine system
Secrete hormones which affect the cell releasing the hormone/protein.
- Autocrine secretion
- Paracrine system
- Endocrine glands
- Thyroid glands
- Autocrine secretion
What type of adenomas can occur in the anterior pituitary gland?
(hint: think of the hormones produced in the pituitary gland)
- Prolactinoma (most common) - results in galactorrhoea (unwanted flow of milk from the breast) + menstrual disturbances
- Growth hormone secreting adenoma - results in gigantism in children, acromegaly in adults
- ACTH secreting adenoma - can result in Cushing’s syndrome
Why can a thyroid gland enlargement lead to a hoarse voice?
The recurrent laryngeal nerve is situated just posteriorly to the thyroid gland.
Thyroid gland pressing on this can cause a hoarse voice.
What is chronic lymphocytic thyroiditis?
Hashimoto’s
Autoimmune chronic inflammation of the thyroid gland due to autoantibodies attacking the thyroid gland.
Enlarged gland, more common in women.
Many patients become hypothyroid.
Hashimoto’s gives an increase risk of what?
Papillary thyroid carcinoma
most common thyroid malignancy
What is diffuse hyperplasia?
Grave’s disease
Autoimmune process resulting in hyperthyroidism and diffuse hyperplasia of the follicular epithelium (responsible for 80% of hyperthyroidism).
More common in females.
Diffuse enlargement of thyroid gland.
What happens to T3, T4, TSH levels in Grave’s disease?
T3 + T4 = ↑
TSH = ↓
Enlargement of the thyroid with varying degrees of nodularity, where patients are mostly euthyroid (normal hormone level, not hypo/hyper).
Multinodular Goitre
Benign tumour of follicular epithelium of thyroid.
Solitary nodule on one lobe, usually a cold nodule on radioactive imaging.
Follicular adenoma
cold nodule = non-functioning so show up as defects in the scan since there is little activity
What is the most common malignant tumour of the thyroid?
What mutation leads to the most aggressive type of this tumour?
Papillary carcinoma
BRAF V600E mutation
What is the difference between Follicular carcinomas and Hurthle Cell carcinomas?
Hurthle cell carcinoma =
significant incidence of cervical lymph node metastases
Spread via lymph + blood
Worse prognosis
Follicular carcinoma =
only spread via blood
Hyperplasia of the glands with elevated PTH in response to hypocalcemia.
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Primary hypoparathyroidism
- Secondary hyperparathyroidism
Seen in renal insufficiency, malabsorption, vitamin D deficiency
Excessive secretion of parathyroid hormone from one or more glands.
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Primary hypoparathyroidism
- Primary hyperparathyroidism
gland itself is abnormal
Adenoma in association with longstanding secondary hyperparathyroidism
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Secondary hypoparathyroidism
- Tertiary hyperparathyroidism
Malignant tumour derived from parathyroid parenchymal cells.
Parathyroid carcinoma
What is Cushing’s syndrome caused by?
Prolonged exposure to cortisol
An exogenous cause of Cushing’s syndrome is excessive glucocorticoid medication.
Give 2 endogenous causes.
- Tumour in adrenal gland
- Ectopic ACTH releasing tumour
- ACTH secreting pituitary adenoma
Give 8 signs and symptoms of Cushing’s syndrome.
- Hypertension
- Moon face
- Central obesity
- Buffalo hump
- Weak muscles
- Osteoporosis
- Insomnia
- Excess sweating
- Mood swings
- Headaches
- Chronic fatigue
- Increased hair growth (women)
- Irregular menstruation (women)
What is Conn’s syndrome?
Hyperaldosteronism
excess aldosterone production, resulting in low renin levels.
What is Addison’s Disease?
Hypoadrenalism
Primary adrenal cortical insufficiency = lack of adrenal gland formation, adrenal destruction
Secondary = failure of ACTH secretion
Treated with long term steroid replacement
What is the triad in Addison’s Disease?
- Hyperpigmentation
- Postural hypotension
- Hyponatraemia (low sodium)
Adrenal cortical adenomas can cause what 2 conditions?
- Conn’s syndrome - aldosterone producing tumours
2. Cushing’s syndrome - cortisol producing tumours
Catecholamine secreting tumour arising from adrenal medulla.
Phaeochromocytoma
catecholamines are dopamine, epinephrine, norepinephrine
Low PTH levels and low calcium levels are commonly seen in what condition?
Hypoparathyroidism
A T-score of less than -2.5 on a DEXA scan indicates which disease condition?
Osteoporosis
Low thyroxine, Low TSH = ?
Pituitary failure
Secondary hypothyroidism
Low thyroxine, High TSH = ?
Unresponsive thyroid
Primary hypothyroidism
High thyroxine, Low TSH = ?
Thyroid gland overproduction
Primary hyperthyroidism
High thyroxine, High TSH = ?
Pituitary gland overproduction / feedback fail
Secondary hyperthyroidism
What can be missed by using TSH as a front line test?
Secondary hypothyroidism
since they have normal TSH levels, but low T4.
How often should Thyroid function tests (TFTs) be repeated in healthy patients?
Every 3 years
Why should TFTs not be measured in hospitalised patients unless a thyroid problem is suspected?
Sick euthyroid disease
Patients will have abnormalities in their thyroid function tests tests suggesting they have a thyroid problem despite being euthyroid.
The abnormalities are due to their other illnesses.
Therefore you will incorrectly diagnose someone of a thyroid problem.
Disease which presents with excessive and often episodic release of catecholamines.
Phaeochromocytoma
What do you measure to diagnose phaeochromocytomas?
Plasmametanephrines
What is Whipple’s triad?
Diagnosis of hypoglycemia
- Signs + symptoms of hypoglycemia
- Low blood glucose level
- Resolution of symptoms once glucose level rises
Most common tumours arising from the islets of Langerhans.
How is it diagnosed?
Insulinoma
Simple fasting blood test.
low blood sugar with high insulin = insulinoma
Diabetes is characterized by hyperglycaemia.
True or False?
TRUE
Which of these is NOT a pancreatic islet cell?
- Alpha cells
- Beta cells
- Chief cells
- Delta cells
- F cells
- Chief cells
alpha cell = glucagon
beta cells = insulin
delta cells = somatostatin
F cells = pancreatic polypeptide
What fasting glucose value is diagnostic of diabetes?
≥ 7 mmol/litre
≥ 11.1 mmol/litre
≥ 5 mmol/litre
≥ 9.1 mmol/litre
≥ 7 mmol/litre
≥ 11.1 mmol/litre = random glucose diabetes diagnosis
What is the oral glucose tolerance test (OGTT)?
- Fasting glucose is measured.
- 75g of glucose is ingested
- Blood glucose levels are measured 2 hours later
≥ 11.1 mmol/litre = diabetic
HbA1c (glycated haemoglobin) reflects average plasma glucose over the previous 8 to 12 weeks.
What HbA1c value is diagnostic of diabetes?
≥ 11.1 mmol/mol
≥ 20 mmol/mol
≥ 41 mmol/mol
≥ 48 mmol/mol
≥ 48 mmol/mol = diabetes
≥ 41 and <48 = pre-diabetes
Where is insulin produced?
Beta cells in Islet of Langerhans (pancreas)
What antibodies measure are used to measure/diagnose type 1 diabetes?
- IAA - Insulin autoantibodies
- GAD 65 (and 67) - Glutamic acid decarboxylase autoantibodies
- IA-2 - Islet antigen-2 autoantibodies
- ZnT8 transporter autoantibodies
(having or not having antibodies does NOT diagnose diabetes if they do not come with symptoms)
Type of diabetes that has a rapid onset and presents with wight loss and ketoacidosis.
Type 1 Diabetes Mellitus
no insulin production
Type of diabetes which presents over a few months with minimal weight loss and can present with vision loss/foot ulcers/fungal infection.
Type 2 Diabetes Mellitus
some insulin production, but cells are not responsive to it
How is gestational diabetes diagnosed?
Symptoms:
1. Hyperglycemia and diabetes first detected in pregnancy
Diagnosis:
1. Oral glucose tolerance test (OGTT)
(HbA1c is NOT used, isn’t very reliable in pregnancy)
What are 3 actions that glucagon has?
- Increases secretion of insulin + growth hormone
- Reduces intestinal motility and gastric acid secretion
- Increases glucose levels (glycogenolysis, gluconeogenesis, lipolysis)
Which of these stimulate glucagon release and which inhibit it?
- Amino acids
- Beta adrenergic stimulation
- Insulin
- Gastrin
- CCK
- Cortisol
- Somatostatin
- Glucose
- Ketones
- Amino acids
- Free fatty acids
- Fasting, hypoglycaemia
- Exercise
Stimulate glucagon:
- Amino acids
- Beta adrenergic stimulation
- Gastrin
- CCK
- Cortisol
- Fasting, hypoglycaemia
- Exercise
Inhibit glucagon:
- Insulin
- Free fatty acids
- Ketones
- Glucose
- Somatostatin
Which of these hormones raise blood glucose levels?
- Glucagon
- Insulin
- Epinephrine
- Cortisol
- Growth hormone
ALL except insulin
hypothalamus is the homeostasis centre for all of these hormones
What is commonly measured to assess the degree of long term glycaemic control?
Glycated haemoglobin
Hereditary iron overload storage disorder that can result in diabetes?
Haemochromatosis
Class of drugs used in the management of osteoporosis that can sometimes result in osteonecrosis of the jaw?
Bisphosphonates
primary therapy used
Cells that are responsible for the breakdown of bone and are critical for its repair and maintenance?
Osteoclasts
What is the main carrier of protein bound calcium in the blood?
Albumin
FSH releasing factor is secreted by?
Hypothalamus
The spongy inner layer of bone is called?
Trabecular bone
The hard outer layer of bone is called?
Cortical bone
What is an osteon?
Microscopic columns of osteoblasts + osteocytes that make up cortical bone.
Blood vessels + nerves travel through the central canals (Haversian canals) of these osteons.
An inorganic component of bone which gives rigidity.
Hydroxyapatite
Osteoid is an unmineralised organic support tissue in bone made by osteoblasts.
What material does it mainly consist of?
Type 1 Collagen
What is the name of osteoblasts that become buried/trapped within the matrix?
Osteocytes
Cells which create and repair new bone.
Osteoblasts
Cells which break down bone and increase blood calcium levels - critical for repair and maintenance of bone.
Osteoclasts
What enzymes do osteoclasts produce?
- Tartrate resistant acid phosphatase (TRAP)
- Alkaline phosphatase
- RANK
- Cathepsin K
- Procollagen type 1 propeptides (P1NP)
- Tartrate resistant acid phosphatase (TRAP)
- Cathepsin K
(alkaline phosphatases + P1NP are made by osteoblasts)
(RANK ligands are not enzymes, they are signalling molecules that regulate osteoclast activity)
Name the 4 main stages of the bone cycle?
- Resting
- Resorption
- Osteoid formation
- Mineralisation
(cycle restarts)
With increasing age, bone formation increases and bone resorption decreases.
True or False?
FALSE
bone formation ↓
bone resorption ↑
(even greater bone loss in women after menopause)
What cell releases alkaline phosphatase?
Osteoblasts
involved in mineralisation
The concentration of what molecule released by osteoblasts, can be used to measure osteoblast activity?
Procollagen type 1N propeptide (P1NP)
↑ levels with ↑ osteoblast activity
vice versa
A T-score of -1.0 and above on a DEXA scan indicates what?
Normal bone density
A T-score between -1.0 and -2.5 on a DEXA scan indicates which disease condition?
Osteopenia
thinning of the bones - not quite osteoporosis
A systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture.
Osteoporosis
Alendronate, Risendronate, Ibandronate, IV Zoledronic acid. These are all what class of drug used in osteoporosis management?
Bisphophonates
What bone marker is used to monitor compliance/response to anti-resorptive therapy
CTX
collagen cross-linking molecule, released with bone resorption
What are 5 presenting symptoms of bone metastases?
- Pain - usually worse at night + gets better with movement
- Broken bones - fractures with minimal/no trauma
- Numbness, paralysis, trouble urinated - metastatic spinal cord compression
- Loss of appetite, nausea, thirst, confusion, fatigue - symptoms of hypercalcaemia
- Anaemia - disruption of bone marrow
What are the 2 types of bone metastases?
- Osteolytic - destruction of normal bone (high calcium levels)
- Osteoblastic - deposition of new bone
What blood test would you do in anyone with a high calcium level?
Parathyroid hormone (PTH) blood test.
When calcium levels are low, PTH is released to increases blood calcium levels.
If calcium is high and PTH is high, there is a problem with the feedback mechanism or the parathyroid glands have an issue.
In lytic bone metastases, there would be high calcium with low PTH.
What happens to calcium and PTH levels in Primary hyperparathyroidism?
Calcium ↑
PTH ↑
What is Paget’s Disease?
Rapid bone turnover and formation leading to abnormal bone remodelling.
(elevated alkaline phosphatase reflecting increased bone turnover)
What would be the best treatment for Paget’s disease and how would it be monitored?
Bisphosphonates - they reduce osteoclastic activity, which also reduces osteoblastic activity.
Alkaline phosphatase (easiest to measure) / P1NP
What is Osteomalacia?
Lack of mineralisation of bone.
Due to:
- Insufficient calcium absorption from intestine - poor diet or Vit D deficiency/resistance
- Excessive renal phosphate excretion
What is the purpose of ‘adjusted calcium’ in blood tests?
- Calcium binds strongly to albumin, therefore if albumin levels are low, the total calcium level will appear to be low in a blood test.
- The adjusted calcium value is an equation which compensates for the change in serum albumin.
Low calcium and magnesium levels trigger PTH release from the parathyroid glands.
What effect does PTH have?
- PTH acts on bone to increase resorption of Ca + PO4
- PTH acts on kidneys to increase reabsorption of Ca from filtrate + increase excretion of PO4
- PTH also acts on kidneys to increase the conversion of vitamin D to its active form - which increases Ca + PO4 absorption in the gut
The net effect of PTH is to increase serum calcium and decrease serum phosphate.
Which of these is NOT a regulator of calcium and phosphate homeostasis?
- Calcitonin
- Oestrogen
- MGD23
- FGF23
- PTH
- Vitamin A
- Vitamin D
MGD23 (made up) + vitamin A
What is Chvostek’s sign?
Sign for hypocalcaemia - tapping over the facial nerve causes twitching of facial muscles (tetany).
(Trousseau’s sign - spasm of wrist + hand after compressing forearm)
What are the signs and symptoms of hypercalcaemia?
STONES - renal stones
BONES - bone pain + osteoporosis
MOANS - lethargy, fatigue, depression
GROANS - abdo pain, constipation, nausea, vomiting
What ion deficiency can present with severe muscle weakness, respiratory muscle failure and rhabdomyolysis?
Phosphate deficiency
What effect will severe hypomagnesaemia have on PTH and calcium levels?
PTH release inhibited, causing hypocalcaemia.
↓ magnesium = ↑ PTH release
↑ magnesium = ↓ PTH
HOWEVER, PTH release is magnesium dependent
What are the primary regulators of calcium and phosphate homeostasis?
PTH
Vitamin D
2.2 - 2.6 mmol/L is the normal range for what ion?
Total plasma calcium
Calcium > 3.5 mmol/L or < 1.6 mmol/L is a medical emergency requiring immediate treatment
