Chem Path Flashcards
Normal pH range
7.35 - 7.45
Normal PCO2
4.7 - 6kPa
Normal Bicarbonate
22 - 30 mmol/L
Normal PO2
10 - 13 kPa
Blood gas results in Metabolic Acidosis
pH
HCO3
CO2
pH LOW
HCO3 LOW
CO2 normal or LOW in compensation
Causes of Metabolic Acidosis (4)
- DKA - increased H+ production
- Renal tubular - decreased H+ excretion
- Intestinal fistula - decreased HCO3
- Lactate build up
Blood gas results in Respiratory Acidosis
pH
HCO3
CO2
pH LOW
HCO3 normal or HIGH in compensation
CO2 HIGH
Causes of Respiratory Acidosis (4)
- Impaired gas exchange e.g. pneumonia, COPD
- Poor perfusion
- Decreased ventilation e.g. head injury
Blood gas results in Metabolic Alkalosis
pH
HCO3
CO2
pH HIGH
HCO3 HIGH
CO2 normal/High
Causes of Metabolic Alkalosis (3)
- D&V
- Pyloric stenosis - babies vomit up all their stomach acid
- hypokalaemia
Blood gas results in Respiratory Alkalosis
pH
HCO3
CO2
pH HIGH
HCO3 normal/LOW
CO2 LOW
Causes of Respiratory Alkalosis (2)
- Mechanical ventilation
2. Hyperventilating/Panic attack - blow off all your CO2
Why look at the PO2?
Gives an indication of lung function, and tissue oxygenation
What's the problem? pH 6. 90 (7.35-7.45) H+ 126 nmol/l (35-46) pCO2 3.0 kPa (4.7-6.0) pO2 24.0 kPa (10.0-13.3) Bicarbonate 6 mmol/l (22-30)
Metabolic Acidosis with partial respiratory compensation
What's the problem? pH 7. 55 (7.35-7.45) H+ 28 nmol/l (35-46) pCO2 8.2 kPa (4.7-6.0) pO2 10.0 kPa (10.0-13.3) Bicarbonate 51 mmol/l (22-30)
Metabolic Alkalosis with partial respiratory compensation
What's the problem? pH 7. 55 (7.35-7.45) H+ 28 nmol/l (35-46) pCO2 3.0 kPa (4.7-6.0) pO2 14.4 kPa (10.0-13.3) Bicarbonate 20 mmol/l (22-30)
Respiratory Alkalosis
What’s the problem?
72 year old man
Long history of chronic obstructive airways disease
On diuretics for cardiac failure
Potassium 2.6 mmol/l (3.5-5.5)
pH 7. 41 (7.35-7.45) H+ 39 nmol/l (35-46) pCO2 10.4 kPa (4.7-6.0) pO2 7.8 kPa (10.0-13.3) Bicarbonate 47 mmol/l (22-30)
Which?
Normal
Metabolic Acidosis
Respiratory Acidosis
Metabolic Alkalosis
Respiratory Alkalosis
Mixed metabolic acidosis and respiratory acidosis
Mixed metabolic alkalosis and respiratory alkalosis
Mixed metabolic alkalosis and respiratory acidosis
Mixed metabolic acidosis and respiratory alkalosis
Mixed metabolic alkalosis and respiratory acidosis
A young woman was admitted to hospital 8 hours after she had taken an overdose of aspirin. Arterial blood: pH 7. 46 (7.35-7.45) H+ 35 nmol/l (35-46) pCO2 2.0 kPa (4.7-6.0) pO2 17.8 kPa (10.0-13.3) Bicarbonate 10 mmol/l (22-30)
Normal
Metabolic Acidosis
Respiratory Acidosis
Metabolic Alkalosis
Respiratory Alkalosis
Mixed metabolic acidosis and respiratory acidosis
Mixed metabolic alkalosis and respiratory alkalosis
Mixed metabolic alkalosis and respiratory acidosis
Mixed metabolic acidosis and respiratory alkalosis
Mixed metabolic acidosis and respiratory alkalosis
Arterial blood: pH 6. 93 (7.35-7.45) H+ 116 nmol/l (35-46) pCO2 9.7 kPa (4.7-6.0) pO2 65.8 kPa (10.0-13.3) Bicarbonate 15 mmol/l (22-30)
Normal
Metabolic Acidosis
Respiratory Acidosis
Metabolic Alkalosis
Respiratory Alkalosis
Mixed metabolic acidosis and respiratory acidosis
Mixed metabolic alkalosis and respiratory alkalosis
Mixed metabolic alkalosis and respiratory acidosis
Mixed metabolic acidosis and respiratory alkalosis
Mixed metabolic alkalosis and respiratory acidosis
How to calculate the anion gap?
Normal range?
(Na+ + K+) - (Cl- + HCO3)
14 - 18mmol/L
Causes of raised anion gap metabolic acidosis?
a) Endogenous (3)
b) Exogenous (MUD PILES)
a) DKA
Lactic acidosis
Starvation
b)
Methanol
Uraemia
Drugs
Paracetamol Insecticides Lithium Ethanol Salicylates (aspirin)
How to measure Osmolality?
2(Na + K) + urea + glucose
How to measure the osmolar gap?
Measure Osmolality - Calculated Osmolarity
What’s the normal osmolar gap?
What could cause an increased osmolar gap?
extra solute present in the plasma e.g. ethanol, methanol
What is Osmolality? Units?
Measured total number of particles present in a solution mmol/kg
What is Osmolarity? Units?
Calculated total number of particles present in a solution mmol/L
Normal range for serum osmolality?
275 - 295 mmol/kg
Normal range for sodium?
135 - 145 mmol/L
Pathogenesis of HYPOnatraemia?
increased extracellular water, dilutionary effect
Level of severe HYPOnatraemia?
Signs of HYPOnatraemia? (4)
- nausea and vomiting
- confusion
- seizures
- coma
In true HYPOnatraemia will the osmolality be high or low?
LOW
Clinical features of HYPOvolaemia? (7)
- low BP
- tachycardia
- postural hypotension
- reduced skin turgor
- dry mucous membranes
- confusion/drowsiness
- reduced urine output
Clinical signs of HYPERvolaemia? (3)
- raised JVP
- bibasal crackles
- peripheral oedema
Classification of hyponatraemia (3)
- HYPERvolaemic
- EUvolaemic
- HYPOvolaemic
Causes of HYPERvolaemic HYPOnatraemia? (3)
- Heart failure
- Cirrhosis
- NephrOtic syndrome
Causes of HYPOvolaemic HYPOnatraemia? (3)
- D&V
- diuretics
- salt losing nephropathy
Causes of SIADH? (4)
- CNS - trauma, inflammation, abscess
- Lung - pneumonia, abscess, small cell lung Ca
- Malignancies - lymphoma, Ewing’s sarcoma, lung, GI, GU
- Drugs - SSRI, TCA, PPI, opiates, amitriptyline
Diagnostic test for SIADH?
Short SynACTHen test
How would you treat a HYPOvolaemic HYPOnatraemic patient?
Replace with 0.9% N.Saline
How would you treat a HYPERvolaemic HYPOnatraemic patient?
Fluid restrict and treat underlying cause
What must you NOT do when correcting sodium?
why?
Serum Na must NOT be corrected > 12 mmol/L in the first 24 hours
Risk of osmotic demyelination (central pontine myelionlysis)
What are the effects of central pontine myelionlysis?
- quadriplegia
- pseudobulbar palsy
- seizures
- coma
- death
Drugs used to treat SIADH? (2)
- Vaptans
2. Demeclocyline
What are the two main stimuli for ADH secretion?
a. Reduced bld volume & reduced serum osmolality
b. Increased bld volume & increased serum osmolality
c. Increased bld volume & reduced serum osmolality
d. Reduced bld volume & increased serum osmolality
d. Reduced bld volume &; increased serum osmolality
Causes of hyponatraemia post-surgery? (2)
- dilutionary due to over hydration with hypotonic IV fluids
- transient increase in ADH due to stress of surgery
Clinically HYPERnatraemic?
> 145mmol/L
Causes of HYPOvolaemic HYPERnatraemia?
- GI
- Skin
- Renal
GI - vomiting, diarrhoea
Skin - excessive sweating, burns
Renal - loop diuretics, osmotic diuresis
Causes of EUvolaemic HYPERnatraemia?
- resp
- skin
- renal
- resp - tachypnoea
- skin - excessive sweating, fever
- renal - DI
Causes of HYPERvolaemic HYPERnatraemia? (2)
- Hypertonic saline
2. Conn’s syndrome - mineralocorticoid syndrome
Signs of HYPERnatraemia? (6)
- lethargy
- thirst
- irritability
- confusion
- coma
- fits
What investigations would you order in a patient with suspected diabetes insipidus?
a. Serum glucose (exclude diabetes mellitus)
b. Serum potassium (exclude hypokalaemia)
c. Serum calcium (exclude hypercalcaemia)
d. Plasma & urine osmolality
e. Water deprivation test
e. Water deprivation test
Symptoms of DI? (2)
polyuria
polydipsia
Types of DI?
- Cranial - lack of ADH
2. Nephrogenic - insensitivity to ADH
Causes of cranial DI? (3)
- head trauma
- tumour
- surgery
How does cranial DI respond to desmopressin?
ability to concentrate urine
What is Psychogenic Primary Polydipsia?
- response to 8 hr fluid deprivation test?
common in mentally ill patients, institutionalised patients
continuous feeling of thirst, will seek fluids from any source possible
able to concentrate urine
Cause of EUvolaemic HYPOnatraemia? (3)
- hypothyroidism
- SIADH
- adrenal insufficiency
Normal range of potassium?
3.5 - 5.5mmol/L
What hormones are involved in potassium homeostasis? (2)
- Aldosterone
2. Angiotensin II
ECG change associated with HYPERkalaemis?
Peaked T waves
Causes of HYPERkalaemia? (7)
- excessive intake
- acidosis
- insulin shortage
- rhabdomyolysis
- Addison’s disease
- reduced GFR - renal/cardiac failure
- drugs
Drugs that can cause HYPERkalaemia? (4)
- ACEi, ARB, NSAIDs, K+ sparring diuretics
Clinical features of HYPOkalaemia? (3)
- muscle weakness
- cardiac arrhythmias
- polyuria/polydipsia
Causes of HYPOkalaemia? (7)
- Hyperaldosterism Conn’s syndrome
- GI loss
- Renal loss
- ostmotic diuresis
- insulin
- beta agonists - salbutamol
- alkalosis
Hyperkalaemia is a side-effect of which of the following drugs?
a. Furosemide
b. Bendroflumethiazide
c. Salbutamol
d. Ramipril
c. Salbutamol
Hypokalaemia is a side-effect of which of the following drugs?
a. Spironolactone
b. Indomethacin
c. Perindopril
d. Furosemide
d. Furosemide
Normal Calcium range
2.2 - 2.6 mmol/L
What happens in response to low calcium? (4)
1. Parathyroids release PTH PTH acts at... 1. Bone - increased calcium resorption 2. Kidney - increases Ca reabsorption - increases PO4 excretion - increases 1a(OH)ase - increases VitD3 3. GI - increases Ca absorption - increases VitD3 absorption
Enzyme required for rate limiting step in activation of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (VitD3)? Where?
1-alpha-hydroxylase
kidney
Hormones that control Calcium homeostasis?
- PTH
2. Calcitriol
In what condition is 1alpha-hydroxylase secreted in the lung?
Sarcoidosis
Causes an increase in Ca2+
Enzyme required to convert cholecalciferol to 25-hydroxycholecalciferol? Where?
25-hydroxylase
Liver
Where is the majority of calcium within the body?
Skeleton (99%)
What percentage of plasma calcium is bound to albumin?
50%
In sepsis, when albumin is low, what can happen to calcium levels?
low calcium
Effects of Vitamin D3? (3)
- increased calcium absorption from gut
- increased phosphate absorption from gut
- bone remodelling
Vitamin D3 deficiency in children?
Ricket’s
Vitamin D3 deficiency in adults?
Osteomalacia
What happens to Ca/PO4/ALP/PTH in Vit D deficiency?
Low VitD3 Low Ca Low PO4 High PTH High ALP
Clinical features of Osteomalacia? (3)
Pathonogmonic?
- Boen pain
- myalgia
- increased risk of fractures
Looser’s zones
Clinical features of Ricket’s? (4)
- bowing of bones
- widened epiphyses at the wrist
- costochondral swelling
- myopathy
Causes of Osteomalacia? (4)
- renal failure
- lack of sunlight
- chappati’s
- anticonvulsants (sodium valproate) breakdown Vit D3
What is Osteoporosis?
Loss of bone density, associated with age
What happens to Ca/PO4/ALP/PTH in Osteoporosis?
All normal
Clinical features of Osteoporosis? (3)
- increased liklihood of fractures
- Typical NOF
- Typical Colle’s
Diagnosis of Osteoporosis?
Osteopenia?
DEXA scan
T
Risk factors associated with Osteoporosis?
- Age
- Childhood illness, failure to reach peak bone density
- Early menopause
- sedentery lifestyle
- smoking
- alcohol
- low BMI
- endocrine - Cushings, hyperprolactinaemia, thyrotoxicosis
- steroids
Treatment of Osteoporosis?
Bisphosphonates e.g. Alendronate
Symptoms of HYPOcalcaemia? (3)
Signs (2)
- perioral parasthesiae
- carpopedal spasm
- neuromuscular excitability
- Trousseau’s
- Chvostek’s
What is Trousseau’s sign?
flexion of wrist & metacarpal joints and adduction on fingers when BP cuff is applied
due to hypocalcemia
What is Chvostek’s sign?
twitch of facial nerve when masseter at the angle of the jaw is tapped
due to hypocalcemia
What happens in response to high calcium?
example
Parathyroids release less PTH
e.g. in malignancy, when there is a high calcium, PTH is suppressed
What’s the commonest cause of hypercalcemia?
primary hyperparathyroidism
Causes of primary hyperparathyroidism (3)
Most common?
- parathyroid adenoma
- parathyroids hyperplasia
- parathyroid carcinoma
adenoma (80%)
Association with parathyroid hyperplasia?
MEN1
Clinical features of HYPERcalcaemia? (6)
Bones - pain Groans - psychogenic Moans - abdominal pain - constipation, pancreatitis Stones - renal polyuria muscle weakness
Types of hypercalcaemia in malignancy? (3)
- Humoral hypercalcaemia due to atopic secretion of PTHrP e.g. small cell lung cancer
- Metastases to the bone e.g. breast
- Haematological malignancies e.g. myeloma
What happens to Ca/PO4/ALP/PTH in Myeloma?
HIGH Ca
HIGH PO4
Normal ALP
Normal PTH
What happens to Ca/PO4/ALP/PTH in Bone metastasis?
HIGH Ca
LOW PO4
HIGH ALP
Normal PTH
What causes secondary hyperparathyroidism?
How?
CKD causing renal osteodystrophy
Damaged kidney doesn’t produced sufficient 1alpha-hydroxylase to activate VitD3 therefore calcium falls
A fall in Calcium causes an increase in PTH
What is tertiary hyperparathyroidism?
When after sustained time of hyperparathyroidism, PTH is then secreted excessively causings an elevated Ca2+
What happens to Ca/PO4/ALP/PTH in secondary hyperparathyrodism?
LOW Ca
HIGH PO4
HIGH PTH
HIGH ALP
What happens to Ca/PO4/ALP/PTH in tertiary hyperparathyroidism?
HIGH Ca
LOW PO4
Norm/high ALP
HIGH PTH
What is Paget’s disease?
remodelling of the bone with both increase osteoblast & osteoclast activity
Clinical features of Paget’s Disease? (8)
- bone pain
- bone warmth
- bone deformation
- increased risk of fracture
- enlarged skull
- deafness
- blindness
- increased risk of malignancy
- increased cardiac output
What happens to Ca/PO4/ALP/PTH in Paget’s Disease?
Norm Ca
Norm PO4
HIGH ALP
Norm PTH
Which has the lowest calcium?
a. Primary hyperparathyroidism
b. Secondary hyperparathyroidism
c. Osteoporosis
d. Pagets disease of the bone
e. Breast cancer
b. Secondary hyperparathyroidism
What causes HYPOparathyroidism?
a) primary
b) secondary
a) Di George syndrome - due to malfunction parathyroid glands
b) post-thyroidectomy
What happens to Ca/PO4/ALP/PTH in HYPOparathyroidism?
LOW Ca
HIGH PO4
Norm ALP
LOW PTH
Risk factors for developing renal stones (5)
- dehydration
- abnormal pH of urine
- urine infection
- renal tubular acidosis
- anatomical abnormalities
Most common type of renal stone? X-ray appearance?
Mixed - radio-opaque
Type of renal stones that are radiolucent?
Uric acid, cysteine
Type of renal stones formed due to UTI?
Staghorn - triple phosphate “struvite”
Enzyme raised in acute pancreatitis?
amylase
Marker of muscle damage?
creatine kinase
Pathological causes of raised CK? (4)
- Duchenne’s Muscular dystrophy
- MI
- Rhabdomyolysis
- Statin related myopathy
Causes for ALP to be raised? (4)
Increased activity in…
- Liver
- Bone
- Intestine
- Placenta
Physiological causes of raised ALP? (2)
- Pregnancy
2. Childhood growth spurt
Pathological causes of raised ALP?
a) Bone (6)
b) Liver (4)
a) metastasis osteomyelitis osteomalacia Pagets fractures tumours
b) hepatitis
cirrhosis
cholestasis
tumours
Marker of myocardial injury?
Troponin
When do you measure Troponin?
6 hrs
12 hrs
post-onset of chest pain
remains elevated fro 3 - 10 days
Diagnostic Criteria for MI?
Rise in Troponin and gradual fall with at least one of the following symptoms
- ischaemic symptoms
- pathologic Q waves of ECG
- ECG changes
- coronary artery intervention
Markers of liver cell damage (5)
AST ALT ALP GGT Bilirubin
Marker of liver function (3)
Glucose
Clotting
Albumin
Marker elevated in chronic alcohol disease?
GGT
When are AST/ALT raised?
when hepatocytes die
What’s the AST:ALT in alcoholic liver disease?
2:1
What’s the AST:ALT in viral liver disease?
Which marker is elevated in cholestasis?
ALP
What are porphyrias?
What cell types? (2)
a group of disorders due to a deficiency in enzymes in the make up of Haem
causing a build up of toxic haem precursors
- hepatic
- erythroid
Types of porphyrias? (3)
- build up of Aminolaevulinic Acid (ALA)
- build up of Porphobilinogen (PBG)
- build up of Porphrinogens
Areas affected by Porphyrias?
a) build up of ALA/PBG
b) build up of porphrinogens
- neuro-visceral
2. skin
Colour of
a) porphrinogens
b) porphyrins
a) colourless
b) highly coloured
What is Acute Intermittent Porphyria?
inheritance
enzyme deficiency
build up of? (2)
Autosomal dominant
Hydroxymethylbilane synthase (HMB synthase)
1. ALA
2. PBG
Overall area affected in Acute Intermittent Porphyria?
Symptoms (10)
Signs
- N&V
- abdo pain
- confusion
- psych disturbances
- seizures
- tachycardia
- hypertension
- muscle weakness
- constipation
- urinary incontinence
Port wine urine
Precipitating factors of Acute Intermittent Porphyria? (5)
ALA synthase inhibitors
- steroids
- ethanol
- barbiturates
- stress - surgery/infection
- reduced calorie intake
Hereditary Coproporphyria
- inheritance
- build up of
- symptoms
- what skin lesion?
autosomal dominant
porphyrins
neurovisceral and skin lesions
blistering and skin fragility
Variegate Porphyria
- inheritance
- build up of
- symptoms
- what skin lesion?
autosomal dominant
porphyrins
neurovisceral and skin lesions
blistering and skin fragility
Non-acute porphyrias? (3)
- area affected?
- symptoms (3)
- precipitating factor
- Congenital Erythopoietic Porphyria
- Erythropoietic Protoporphyria
- Porphyria Cutanea Tarda
skin lesions
- photsensitivity
- itching
- burning
sun exposure
Treatment of acute porphyrias? (2)
- IV carbohydrate
2. Haem arginate
During acute porphyria, the most useful sample to send is…? Blood CSF Urine Muscle biopsy Stool Skin biopsy
Urine
Cutaneous erythema without blisters or bullae, most likely indicates
a. Erythropoietic protoporphyria
b. Congenital erythropoietic porphyria
c. Acute intermittent porphyria
a. Erythropoietic protoporphyria
What occurs first in response to hypoglycaemia?
a. Suppression of insulin
b. Release of glucagon
c. Release of adrenaline
d. Release of cortisol
a. Suppression of insulin
Causes of hyperinsulinaemic hypoglycaemia? (3)
- iatrogenic insulin
- sulfonylurea excess
- insulinoma
What is C-peptide?
a. is the cleavage product of insulin
b. is secreted in equimolar amounts to insulin
c. has a half-life of 2 hours
d. interferes with insulin measurement
b. is secreted in equimolar amounts to insulin
Half life of Insulin?
Half life of C peptide?
4 - 6 mins
30 mins
Causes of hypoinsulinaemic hypoglycaemia with positive ketones? (4)
- alcohol binge with no food
- pituitary insufficiency
- addison’s
- liver failure
Causes of hypoinsulinaemic hypoglycaemia with negative ketones?
non pancreatic neoplams e.g. fibrosarcomata
20 year old female, BMI 17 kg/m2 Lanugo hair noted Finger prick glucose – 3.8mmol/L Routine bloods taken Doctor rung by lab 1 hr later as plasma glucose 2.6 mmol/L
a. Undertakes strenuous exercise regularly
b. Insulinoma
c. Anorexic with poor liver glycogen stores
d. Laxative abuse
c. Anorexic with poor liver glycogen stores
What would the insulin and C-peptide result be if they had been measured ?
a. Low insulin, low C-peptide
b. Low insulin, high C-peptide
c. High Insulin, lowC-peptide
d. High insulin, high C-peptide
a. Low insulin, low C-peptide
What is beta-hydroxybutyrate?
a. End product of insulin metabolism
b. A free fatty acid
c. A triglyceride
d. A ketone body
e. A component of artificial nutrition
d. A ketone body
45 year old lady brought in fitting. Recurrently seen GP in previous months due to weight gain and increased appetite
Husband reports personality change in last few months.
Glucose 1.9 mmol/L
Insulin 35 mu/L
C-peptide 1000 pmol/L
Urine sulponylurea drug screen negative
What is the diagnosis?
a. Insulinoma
b. Cushings syndrome
c. Addison’s disease
d. Sulphonylurea excess
e. Need more information
a. Insulinoma
Associated with insulinoma?
MEN1
What is Non-islet tumour hypoglycaemia?
- lab results (5)
tumour that causes a paraneoplastic syndrome when IG-2 is secreted and binds to IGF-1 and insulin receptors everything low LOW glucose LOW Insulin LOW C-peptide LOW FFAs LOW ketones
Diagnosis of DM Fasting glucose OGTT Random glucose HbA1C
Fasting glucose > 7
OGTT > 11.1
Random glucose > 11.1
HbA1C > 48
Phenytoin
- signs of toxicity (2)
- inication
- interactions
- treatment of toxicity
- Ataxia
- Nystagmus
- seizures
- at high levels, liver becomes saturated and there is a surge in blood levels
- omit/reduce dose
Digoxin
- indication
- signs of toxicity (4)
- interactions
- treatment of toxicity
- arrhythmias
1. Arrhythmias
2. Heart block
3. Confusion
4. Xanthopsia - seeing yellow - levels can increase with hypokalaemia, so reduce dose in elderly/renal failure
- Digibind
Lithium
- indication
- signs of toxicity (5)
- interactions
- treatment of toxicity
Bipolar disorder
- Tremor
- Lethargy
- Fits
- Arrhythmias
- Renal failure
- excretion impaired by hyponatraemia, low renal function and diuretics
- renal failure may need dialysis
Gentamicin
- indication
- signs of toxicity (4)
- interactions
- treatment of toxicity
- uncontrolled infection
1. Tinnitus
2. Deafness
3. Nystagmus
4. Renal failure - mostly use single daily dosing
- omit or reduce dose
Theophylline
- indication
- signs of toxicity (4)
- interactions
- treatment of toxicity
- Asthma
1. Arrhythmias
2. Anxiety
3. Tremor
4. Convulsions - level can be increased by erythromycin, phenytoin, cimetidine
- omit/reduce dose
Vitamin A deficiency
Night blindness
Vitamin D deficiency (2)
- Osteomalacia
2. Rickets
Which steroid is made in the zona fasciculata of the adrenal gland?
Cortisol
Which steroid is made in the zona glomerulosa of the adrenal gland?
Aldosterone
Which steroid is made in the zona reticularis of the adrenal gland?
Cortisol and sex hormones
Where are the catecholamines made in the adrenal gland?
medulla
31 year old presents with profound tiredness. Acutely unwell a few days. Vomiting Na: 125, K: 6.5, U 10, Glucose 2.9mM. FT4 50mU/l
What does this TSH suggest? A. A TSH producing pituitary adenoma B. Graves disease C. A toxic thyroid nodule D. Primary hypothyroidism E. de Quervain’s (viral) thyroiditis.
D. Primary hypothyroidism
Cushing’s syndrome
- excess what?
- causes (3)
- diagnostic test
- diagnostic test suggestive of pituitary adenoma
ACTH
- pituitary adenoma
- ACTH secreting tumour
- iatrogenic steroid use
- Low dose Dexamethasone
- High dose Dexamethasone
Clinical features of Cushing’s? (12)
truncal weight gain moon facies thin skin - easy bruising, striae hirsuitism acne depression & psychosis insomnia oligomenorrhoea proximal myopathy DM osteoporosis
Addison’s syndrome
- deficiency in what? (2)
- causes (5)
- diagnostic test
Cortisol and Aldosterone 1. autoimmune 2. TB 3. adrenal tumour deposits 4. adrenal haemorrhage 5. amyloidosis Short SynACTHen test (cortisol will fail to rise)
Clinical features of Addison’s? (9)
Lab findings in Addison’s? (3)
weight loss fatigue depression vomiting diarrhoea postural hypotension pigmentation vitiligo adrenal cortex atrophy
low sodium
high potassium
low glucose
Why does increased pigmentation of the palmar creases occur in Addison’s?
High ACTH -> high POMC cleavage -> high alpha-MSH -> increased pigmentation of buccal, palmar, scars
Treatment of Addison’s? (2)
- Hydrocortisone to replace cortisol
2. Fludrocortisone to replace Aldosterone
Conn’s syndrome
- excess what?
- causes
- diagnostic test?
Aldosterone
Adrenal tumour of zona glomerulosa
Renin:Aldosterone ratio
Clinical features of Conn’s (3)
uncontrollable hypertension
high sodium
low potassium
Treatment of Conn’s (2)
- Spironolactone (ARB) before surgery
2. Surgery to remove tumour
Phaeochromocytoma
- excess what
- causes
- diagnostic test
Adrenaline/NA
adrenal tumour of the medulla
24hr urinary catecholamines
Clinical features of Phaeochromocytoma (11)
hypertension tachycardia panic sensation nervousness clammy pale arrhythmias headache sweating CNS exciteability seizures
Treatment of Phaeo? (5)
- fluid resuscitation
- 24 hour urinary catecholamine collection
- alpha blockade preparation to prevent hypovolaemic crisis
- beta blockade to tachycardia ++
- surgery
Hypertensive 33 year old.
Na 147, K 2.8, U 4.0. Glucose 4.0 mM
Plasma aldosterone raised.
Plasma renin suppressed.
Diagnosis?
Primary hyperaldosteronism
Conn’s
A 30-year-old woman complains of galactorrhoea and amenorrhoea. A CT scan of her pituitary shows a large (2cm) macroadenoma.
What complication of a large pituitary tumour should you examine for?
Bitemporal hemianopia
A 30-year-old woman complains of galactorrhoea and amenorrhoea. A CT scan of her pituitary shows a large (2cm) macroadenoma.
Her prolactin level comes back at 30,000 (normal
C. Prolactinoma
Clinical features of Prolactinoma? (9)
galactorrhoea oligomenorrhoea amenorrhoea infertility reduced libido osteoporosis headaches pituitary insufficiency bitemporal hemianopia
Diagnosis of prolactinoma? (2)
- Prolactin > 2000mU
2. MRI pituitary
Management of prolactinomas? (2)
- DA agonists e.g. Bromocriptine, Cabergoline
2. Surgery
Side effects of Bromocriptine? (5)
- N&V
- cramps
- psychomotor excitation
- dykinesias
- postural hypotension
Combined Pituitary Function Test (CPFT) - what is it for?
Assesment of the function of the anterior pituitary
a) when suspecting a tumour
b) following tumour surgery
What is involved in CPFT? (3)
- Insulin tolerance Test - adequate GH
- TRH Test - thyroid pathology
- GRH Test - indication of hypopituitarism
Laron dwarfism
- inheritance
- what
autosomal recessive
variant of GH receptor in insensitive to GH
Endocrine Related short stature
- diagnosis (2)
- risks associated with GH therapy (3)
- Insulin tolerance test
- growth charts
- risk of leukaemia
- antibody resistance
- headaches
Types of DI? (3)
- Central/Cranial/Neurogenic - failure to produce ADH
- Nephrogenic - failure to respond to ADH
- Dispogenic - failure to initiate thirst drive due to damage to hypothalamus
Target tissues of thyroid hormone? (9)
- Endo - GnRH, Prolaction secretion
- CNS
- SNS - increases response to NA/Adrenaline
- Bone
- CVS - increases contractility, increase HR
- Skeletal muscle - increases muscular contraction
- Liver - increases gluconeogeneis, glycogenolysis, cholesterol synthesis
- Haematopoetic - increases EPO
- GI - increases gut motility
HYPOthyroidism
- what
- who
- causes (4)
- lab results
destruction/atrophy of thyroid gland F>M 1. autoimmune - antibodies destroy thyroid gland 2. transient due to viral infection 3. iodine deficiency 4. drug induced e.g. lithium, amiodarone
HIGH TSH
LOW T3/T4
Causes of secondary HYPOthyroidism? (4)
- lab results
- post-thyroidectomy
- post pituitary surgery
- Radioiodine
- Drug induced
LOW TSH LOW T3/T4
Hashimotos Thyroiditis
- what
- who
- clinical features
- association
Autoimmune hypothyroidism causing plasma cell infiltration
elderly women
goitre present
initial “hashitoxicosis”
Treatment of HYPOthyroidism?
Replacement with Levothyroxine (T4)
Clinical Features of HYPOthyroidism (10)
- low metabolic rate
- reduced appetite
- weight gain
- low HR
- constipation
- lethargy
- increased sensitivity to cold
- slow speech
- thickened skin
- brittle nails and hair
HYPERthyroidism
- what
- who
- causes (4)
- lab results
increased level of thyroid hormone F>M 1. Grave's 2. Multinodular goitre 3. Toxic adenoma 4. DeQuervain's Thyroiditis 5. Post-partum thyroiditis
LOW TSH HIGH T3/T4
Clinical Features of HYPERthryoidism (10)
increased metabolic rate increased appetitie weight loss exopthalamus/lid lag increased HR diarrhoea tremor low tolerance to heat agitation sweating
What is De Quervain’s thyroiditis?
Symptoms (3)
Self-limiting post-viral thyrotoxicosis
- painful goitre
- malaise
- fever
What is Grave’s disease?
Tsh stimulating antibodies cause an increase in TSH
What is Plummer’s disease?
- associations (2)
toxic multi-nodular goitre
- AF
- heart failure
Which thyroid conditions have high uptake on radioisotope scan? (3)
- Grave’s
- Plummer’s/Toxic Multi-nodular goitre
- Solitary toxic adenoma
Complication of hypothyroidism during pregnancy?
Neonatal cretinism - elevated TSH LOWT3/T4 -> mental retardation, growth arrest, deafness, immature body proportions
Treatment of high uptake HYPERthyroidism?(3)
- Beta blockers
- Carbimazole/Propylthiouracil to block TSH
- Surgery
Thyroid Neoplasms (4)
- Papillary
- Medullary
- Follicular
- Aplastic
Papillary Thyroid Carcinoma
- who
- associations (2)
- treatment
F>M aged 30-40years
1. MEN-1
2. BRAF mutations
Surgery and radioiodine
Follicular Thyroid Carcinoma
- who
- associations (2)
- F>M middle aged
1. aggressive
2. mets to lung & bone
Medullary Thryoid Carcinoma
- associations (2)
- MEN-2
2. Produces calcitonin - lowers calcium
Aplastic thyroid Carcinoma
very aggressive
p53 mutation
elderly population
Vitamin A deficiency
Nigh blindness
Vitamin D deficiency (2)
- Osteomalacia
2. Rickets
Vitamin E deficiency (Tocophenol) (2)
- Anaemia
2. Neuropathy
Vitamin K deficiency
- investigation
Clotting defective
PTT
Thiamin deficiency B1 (3)
- Bert Beri
- Neuropathy
- Wernicke’s encephalopathy
Vitamin B2
Glossitis
Vitamin B6 Pyridoxine (2)
- Dermatitis
2. Anaemia
Vitamin B12
Pernicious anaemia
Vitamin C
Scurvy
Folate deficiency (2)
- Megaloblastic anaemia
2. Neural tube defects
Vitamin B3 Niacin (3)
Pellagra 1. Dementia
- Dermatitis
- Diarrhoea
Iron deficiency
Hypochromic anaemia
Iodine deficiency (2)
- Goitre
2. Hypothyroid
Zinc deficiency
Dermatitis
Copper deficiency
Anaemia
Fluoride deficiency
Dental caries
Phenylketonuria PKU
- what
- screening test
- outcomes
- management
- phenylalanine hydroxyl are deficiency causes a build up of phenylalanine
- Guthrie test
- progressive developmental delay and mental retardation
- dietary avoidance of phenylalanine
Congenital hypothyroidism
- what
- screening test
- presentation (5)
- results (2)
- management
- dysgenesis of thyroid gland, can be due to iodine deficiency or maternal carbimazole
- Guthrie test
- baby has 1. Poor feeding
2. Somnolence
3. Reduced crying
4. Lethargy
5. Constipation - high TSH low T4
- L-thyroxine replacement
Cystic Fibrosis
- mutation
- outcome
- affected organs (5)
- screening test
- CFTR
- viscous secretions which can cause ductal blockages
1. Respiratory tract
2. Pancreas
3. Biliary tract
4. Liver
5. Kidney - Guthrie test
Medium Chain AcylCoA Dehydrogenase Deficiency MCADD
- what
- inheritance pattern
- risks (3)
- screening
- management
- Inherited disorder if fatty acid metabolism, unable to produced ketones -> hypoglycaemia and hypoketouria
1. Stress
2. Illness
3. Exercise - Guthrie test
- avoid fasting, cannot feed >every 8 hours about in first year of life, >10 hours thereafter
What does the Guthrie Test screen for? (5)
Must Heel Prick Small Child MCADD Congenital hypothyroidism PKU Sickle cell CF