Chem path Flashcards
Define hyponatraemia
Serum Na+ < 135mmol/L
most common electrolyte abnormality
Pathogenesis of hyponatraemia
Increased extracellular water due to excess ADH
How does ADH work?
Acts on V2 receptors on collecting duct cells in nephron
Leads to insertion of aquaporin-2 channels
Leads to water retention, increasing extracellular water
What stimulates ADH secretion?
Increased serum osmolality (detected by osmoreceptors, also leads to thirst)
Decreased blood volume/pressure (detected by baroreceptors)
First step in mx of pt with hyponatraemia
Volume status
- hypovolaemic
- euvolemic
- hypervolemic
Compare clinical features of hypo and hypervolaemia
Hypo
- tachycardic
- postural hypotension
- dry mucous membranes
- reduced skin turgor
- confusion/drowsiness
- reduced urine output
- LOW urine Na+ (<20)
Hyper
- raised JVP
- bibasal crackles
- peripheral oedema
What is the most reliable clinical sign of hypovolaemia?
LOW urinary sodium (<20)
Shows the kidney is trying to retain fluid because in hypovolaemia, the body is low in salt AND water
What would alter interpretation of urine sodium?
Diuretic use
Urine can be checked 48hrs after stopping drug
Causes of hypovolaemic hyponatraemia
GI loss (vomiting and diarrhoea)
Diuretics
Salt losing nephropathy
Causes of euvolaemic hyponatraemia
Hypothyroidism
Adrenal insufficiency
SIADH
Causes of hypervolaemic hyponatraemia
Cardiac failure
Cirrhosis
Nephrotic syndrome/renal failure
How does SIADH lead to hyponatraemia?
SIADH describes a state where excess ADH is released
Results in excess retention of water and pt initially becomes hypervolaemic
However, expanded volume stimulates release of natriuretic peptides
Leads to natriuresis; loss of Na+ via urine and water follows
End volume status is euvolaemia w hyponatramia
Causes of SIADH
CNS pathology (tumour, abscess, stroke)
Lung pathology (small cell lung Ca, pneumothorax, PE, chest infection)
Drugs (SSRI, TCA, opiates, PPIs, carbamazepine)
Tumours
Surgery
How is SIADH diagnosed?
Diagnosis of exclusion
- true hyponatraemia (<135)
- low plasma/serum osmolality (<270)
- high urine sodium (>20)
- high urine osmolality (<100) due to natriuresis
- no adrenal/thyroid/renal dysfunction so normal 9am cortisol and normal TFTs
Why do hypothyroid pts become hyponatraemic?
Hypothyroidism leads to reduced cardiac output due to reduced cardiac contractility
Detected by baroreceptors -> ADH release to correct BP
Increased water retention
Why do adrenal insufficient pts become hyponatraemic?
Adrenal insufficiency leads to low aldosterone and cortisol
Low aldosterone -> less salt and water retention in kidney
Low cortisol -> excess ADH release and water retention
What happens to urinary sodium in cardiac failure?
LOW
Secondary hyperaldosteronism occurs due to activation of renin-angiotensin-aldosterone system to keep BP high
Aldosterone promotes water and sodium retention in kidney
Treatment for hyponatraemia
Hypo
- volume replacement with 0.9% saline (NaCl)
Euvo/hyper
- fluid restriction
- treat underlying cause
Signs of severe hyponatraemia
Nausea and vomiting (<134)
Confusion (<131)
Seizures, non-cardiogenic pulmonary oedema (<125)
Coma (<117) and eventual death
expert help needed
Risks of sodium correction treatment
Central pontine myelinolysis if serum sodium corrected faster than 8-10mmol/L in first 24 hours
Water moves too quickly out of cells, affecting CNS gap junctions, inflammatory cells enter via compromised junctions -> osmotic demyelination
Signs of osmotic demyelination
Quadriplegia Dysarthria Dysphagia Seizures Coma Death
*manifest a few days after sodium corrected too quickly
What should you do if sodium is administered too quickly?
Lower Na+ using 5% dextrose
What drugs are used to treat SIADH?
If fluid restriction not enough
- Demeclocycline
- reduce effect of ADH on collecting duct cells
- monitor U&Es due to nephrotoxicity risk - Tolvaptan
- V2 receptor antagonist
- expensive and associated w high risk in serum sodium
What causes hypernatraemia?
Hyper Na+ >145mmol/L
- raised urea, albumin and PCV
Caused by unreplaced water loss
- GI loss
- Sweat loss
- Renal loss: osmotic diuresis, diabetes insipidus (reduced ADH release/action)
Typically in pts who don’t drink when dehydrated, i.e. elderly, children
What is approximate fluid balance in the body?
60-40-20
60% of total body weight = water
40% of body weight = intracellular
20% of body weigh = extracellular (needs salty water for cells to survive in)
Osmolality vs Osmolarity defintions
Osmolality
- total no. of particles in solution, measured with an osmometer (mmol/kg)
Osmolarity
- calculated (mmol/L)
Osmolarity equation
2(Na+ + K+) + urea + glucose
*anions will roughly equal cations thus cations doubled
What are the causes of hyponatraemia based on osmolality?
High osmolality
- glucose/mannitol infusion
Normal osmolality
- spurious result, drip arm sample, pseudohyponatraemia (hyperlipidaemia/paraproteinaemia)
Low osmolality
- true hyponatraemia
What is the difference in causes for hypovolaemic hyponatraemia based on urine sodium?
High urine Na+ (>20)
- RENAL
- diuretics, addison’s, salt-losing nephropathy
- kidney fails to reabsorb sodium so water lost as well
Low urine Na+ (<20)
- NON-RENAL
- vomiting, diarrhoea, excess sweat
- kidney doing best to hold onto Na
Signs of diabetes insipidus
Hypernatraemia (lethargy, thirst, irritability, confusion, coma, fits)
Clinically euvolaemic
Polyuria and polydipsia
Low urine osmolality (<2)
Ix for diabetes insipidus
- Serum glucose (exclude DM)
- Serum K+ (exclude hypokalaemia)
- Serum Ca2+ (exclude hypercalcaemia)
- Plasma and urine osmolality
- 8-hour water deprivation test; DIAGNOSTIC
How is the type of diabetes insipidus confirmed?
8-hour water deprivation test
Normal
- urine osmolality >600, can concentrate
Primary polydipsia
- urine concentrates less than normal
Cranial DI
- Urine osmolality increases >600 ONLY AFTER desmopressin
Nephrogenic DI
- no increase in urine osmolality even after desmopressin
Causes and treatment of diabetes insipidus
Cranial
- lack/no ADH
- surgery, trauma, craniopharyngioma, autoimmune hypohysitis
- mx: desmopressin
Nephrogenic
- insensitive to ADH
- inherited, drugs (lithium, demeclocycline), hypokalaemia, hypercalcaemia
- mx: thiazide diuretics
What are the three most important buffering systems in the body?
Bicarbonate (ECF< glomerular filtrate)
H+ + HCO3- /=/ H2CO3
Haemoglobin (red cells)
H+ + Hb- /=/ HHb
Phosphate (renal tubular fluid/intracellular)
H+ + HPO4- /=/ H2PO4
What is the main system H+ is excreted by the body?
H+ excreted into renal tubules in return for Na+ absorption
Important for kidneys to excrete H+ and regenerate HCO3- to maintain bicarbonate buffering system (only works in short term as uses up HCO3- quickly)
How is HCO3- produced in the body?
From carbonic acid made from CO2 excreted by the lungs (product of metabolism)
CO2 + H2O /=/ H2CO3 /=/ H+ + HCO3-
What results do ABGs produce?
pO2 = partial pressure of oxygen
pCO2 = partial pressure of CO2
pH
Analyser does NOT directly measure bicarbonate; calculates it with equation
What may cause metabolic acidosis?
Increased H+ production (DKA, lactic acidosis)
Decreased H+ excretion (renal tubular acidosis, renal failure)
Bicarbonate loss (intestinal fistula)
How does the body compensate for metabolic acidosis?
Increases resp rate and blow off more CO2 in an attempt to reduce H+
Compensated metabolic acidosis should have a low pCO2
What may cause respiratory acidosis?
Lung pathology that leads to increased CO2
Decreased ventilation, poor lung perfusion, impaired gas exchange
How does the body compensate for respiratory acidosis?
Slightly increasing the bicarbonate concentration
Kidney scompensate by increasing H+ excretion and HCO3- regeneration but slower than respiratory compensation
May see elevated HCO3- and CO2 with normal H+ in compensated respiratory acidosis
What do you expect to see in patients with COPD in an ABG? (not an exacerbation)
Chronic respiratory acidosis with chronically high bicarbonate levels
What may cause metabolic alkalosis?
H+ loss (pyloric stenosis)
Hypokalaemia (K+ main transport agent for H+ exchange - Na/K/ATPase)
Ingestion of bicarbonate (overdose of antacids)
How does the body compensate for metabolic alkalosis?
If hypokalaemic, cannot excrete H+!!
Resp centre will become inhibited leading to a rise in pCO2 for H+ to return to normal
What may cause respiratory alkalosis?
Due to hyperventilation
Anxiety
Artificial ventilation or stimulation of resp centre (rare)
Pregnancy
Altitude
How does the body compensate for respiratory alkalosis?
May see with assisted ventilation - prolonged results in decreased renal H+ and decreased HCO3- generation
Compensation only occurs in chronic cases, H+ returns to normal but pCO2 and HCO3- remain low
Metabolic acidosis ABG
pH: LOW
pCO2: LOW
HCO3-: LOW
Immediate compsenation: hyperventilation
Metabolic alkalosis ABG
pH: HIGH
pCO2: HIGH
HCO3-: HIGH
Immediate compensation: hypoventilation
Respiratory acidosis ABG
pH: LOW
pCO2: HIGH
HCO3-: HIGH (renal delayed compensation)
*normal/high pCO2 worrying - ITU RV/vent support needed
Respiratory alkalosis ABG
pH: HIGH
pCO2: LOW
HCO3-: LOW (renal delayed compsensation)
Role of anion gap in ABGs
Elevated anion gap in metabolic acidosis, helps determine cause
Causes of metabolic acidosis with elevated anion gap
KULT
Ketoacidosis (DKA, alcoholic, starvation)
Uraemia (renal failure)
Lactic acidosis
Toxins (ethylene glycol, methanol, paraldehyde, salicylate)
What ABG changes may these drugs cause?
a) aspirin
b) salicylates
c) opioids
d) loop diuretics
a) Metabolic acidosis (high anion gap)
b) Respiratory alkalosis (brainstem stimulation)
c) Respiratory acidosis (T2 resp failure)
d) Metabolic alkalosis (K+ depletion)
Role of osmolar gap in ABGs
Helpful in differentiating caues of elevated anion gap metabolic acidosis
Elevation suggestive of presence of abnormal solute (alcohol, mannitol, ketones, lactate)
Which hormones regular potassium and where do they come from?
Angiotensin II
Aldosterone
*Angiotensinogen (liver) via renin -> angiotensin I via ACE in lungs -> angiotensin II STIMULATES aldosterone release (adrenals/zona glomerulosa)
What does aldosterone do?
Stimulate Na+ reabsorption (water retention) and K+ excretion
Acts on cortical collecting duct on mineralocorticoid receptor
Na+ channels increase on luminal membrane, more Na+ reabsorbed, lumen electronegative therefore K+ moves down electrogradient and SECRETED
What is normal serum concentration for K+?
- 5-5.0 mmol/L
* K+ most abundant intracellular cation*
ECG changes seen with hyperkalaemia
Loss of P waves
Tall, tented T waves
Broad QRS complexes (late change)
ECG is ‘pulled apart’ to create a ‘sine wave’ if severe/untreated
Mx of hyperkalaemia
Repeat sampling
- may be spurious result due to haemolysis
- repeat if >7
ECG
- check if any changes/arrhythmia
K+ >5.5 w ECG OR K+ >6.5 regardless of ECG triggers:
10ml of 10% calcium gluconate
- stabilise myocardium, prevent arrhythmia
100-200ml of 10-20% dextrose + 10 units of insulin
- drive K+ into cells
- dextrose avoid hypoglycaemia
- note: 50ml 50% dextrose old mx, very irritant
Nebulised salbutamol
- drive K+ into cells
Consider calcium resonium 15g PO or 60g PR
- bind K+ in gut
Treat underlying cause
Causes of hyperkalaemia
Artefact
- spurious result due to haemolysis/EDTA contamination in FBC bottle
Renal impairment
- renal failure as reduced GFR so reduced K+ secretion
- happens late due to compensatory mechanisms
Reduced renin activity
- RARE cause: type 4 renal tubular acidosis
- NSAIDs
Drugs
- ACEi -> less aldosterone
- ARBs -> less angiotensin II, less aldosterone
- spironolactone -> aldosterone antagonists
Low aldosterone
- Addison’s (damaged adrenal cortex)
- Type 4 renal tubular acidosis (low renin)
K+ release from cells
- Rhabdomyolysis
- Acidosis (high H+, K+ leaves cells to take H+ in to normalise pH and maintain gradient)
What care should be taken for patients on digoxin when administrating calcium?
Cardiac monitoring should be performed
IV Ca2+ can precipitate arrhythmias
Causes of hypokalaemia
GI loss
- D&V
Renal loss
- Hyperaldosteronism (Conn’s), Cushing’s (excess cortisol) -> act on MR
- Increased Na+ to distal nephron; drugs, Bartter/Gitelman syndromes
- osmotic diuresis
Redistribution into cells
- insulin
- beta agonists
- alkalosis; opposite mechanism of acidosis (H+ leave cell, K+ enters)
Rare
- renal tubular acidosis type 1 and 2
- hypomagnesaemia
Which drugs and syndromes cause hypokalaemia and why?
Loop diuretics + Bartter syndrome
- blocks triple transporter (Na+/K+/Cl-) in ascending limb of loop of Henle
- Na+ not absorbed loop of Henle so MORE deliver to distal nephron and K+ lost via voltage gradient in exchange
Thiazide diuretics + Gitelman syndrome
- blocks Na+ and Cl- reabsorption in distal convoluting tubule
- more Na+ delivered to distal nephron so K+ lost via voltage gradient in exchange
Clinical features of hypokalaemia
MAP
Muscle weakness
Arrhythmias
Polyuria and polydipsia (low K+ -> nephrogenic DI)
Screening ix to order if pt hypokalaemic + hypertensive
Aldosterone:renin ratio
- 1o hyperaldosteronism; high ratio as renin supressed
- think Conn’s
Can cardiac failure cause hypokalaemia?
Two things happening
- 2o hyperaldosteronism due to excess activation of RAAS -> increase K+ excretion
- Renal hypoperfusion meaning reduced GFR -> reduce K+ excretion
Therefore net clinical effect may not be hypokalaemia; difficult to predict K+ levels in these patients
Can cardiac failure cause hyponatraemia?
Low cardiac output -> baroreceptors detected -> stimulate ADH -> retains water -> dilutes osmolality -> hyponatraemia
Mx of hypokalaemia
K+ 3.0-3.5
- oral KCl (2 SandoK tablets for 48 horus)
- re-check level
K+ <3.0
- IV KCl
- max. rate 10mmol/hour
- highly irritant
Treat underlying cause
How can renal tubular acidosis affect K+?
Type 1
- most severe
- distal failure of H+ excretion and subsequent acidosis
- HYPOKALAEMIA
Type 2
- milder
- failure to reabsorb HCO3- leads to acidosis
- HYPOKALAEMIA
Type 3 irrelevant lol
Type 4
- leads to acidosis HOWEVER aldosterone deficiency/resistance so HYPERKALAEMIA
A 67-year-old man was started on Bendroflumethiazide for hypertension 2 weeks ago. He has had diarrhoea and vomiting for two days. He has dry mucous membranes and reduced skin turgor.
- Sodium: 129 mmol/l
- Potassium: 3.5 mmol/l
- Urea: 8.0 mmol/l
- Creatinine: 100 micromoles/l
Mx plan?
This patient is showing signs of hypovolaemia. He is also hyponatraemic. Causes of hypovolaemic hyponatraemia include D&V, diuretics and salt-losing nephropathy.
Treatment: 0.9% sodium chloride.
A 57-year-old woman has breathlessness, worsened on lying flat. Her past medical history includes an NSTEMI. She is taking ramipril, bisoprolol, aspiring and simvastatin. She has an elevated JVP, Bibasal crackles and bilateral leg oedema.
- Sodium: 128 mmol/l
- Potassium: 4.5 mmol/l
- Urea: 8.0 mmol/l
- Creatinine: 100 micromoles/l
Mx plan?
o Increased urea can suggest reduced GFR aka renal impairment
o Reduced urea can suggest alcoholism
This patient is showing signs of hypervolaemia (clinically). Causes of hypervolaemic hyponatraemia include cardiac failure (likely here), cirrhosis and nephrotic syndrome.
Treatment: fluid restriction, treat the underlying cause.
A 55-year-old man has jaundice. He has a past history of excessive alcohol intake. He has multiple spider naevi, shifting dullness and splenomegaly.
- Sodium: 122 mmol/l
- Potassium: 3.5 mmol/l
- Urea: 2.0 mmol/l
- Creatinine: 80 micromoles/l
Mx plan?
The diagnosis is cirrhosis. Cirrhosis can cause hyponatraemia due to a release in excess nitric oxide. Portal hypertension is associated with a systemic vasodilation due to release of NO – the resulting reduced blood pressure is detected, causing a release in ADH.
Treatment: fluid restriction, treat the underlying cause.
A 40-year-old woman presents with fatigue, weight gain, dry skin and cold intolerance. On examination, she looks pale.
- Sodium: 130 mmol/l
- Potassium: 4.2 mmol/l
- Urea: 5.0 mmol/l
- Creatinine: 65 micromoles/l
Next ix and mx?
This sounds like a diagnosis of hypothyroidism. Reduced cardiac contractility results in a reduced blood pressure, which is sensed by baroreceptors. There is a subsequent release in ADH, and more water absorbed (and hyponatraemia). The patient is euvolaemic. We need to check TFTS.
Treatment: Treat the underlying cause (thyroxine replacement)
A 45-year-old woman presents with dizziness and nausea. On examination, she looks tanned and has postural hypotension.
- Sodium: 128 mmol/l
- Potassium: 5.5 mmol/l
- Urea: 9.0 mmol/l
- Creatinine: 110 micromoles/l
Next ix and mx?
This sounds like adrenal insufficiency; hyponatraemia and hyperkalaemia make us think of hypoadrenalism. The patient is euvolaemic. We should perform a short synACTHen test (in a healthy person, cortisol will shoot up, but in adrenal insufficiency, it won’t).
Treatment: Hydrocortisone and Fludrocortisone (both glucocorticoid and mineralocorticoid replacement).
A 62-year-old man has chest pain, cough and weight loss. He looks cachectic. He has a 30-pack year smoking history.
- Sodium: 125 mmol/l
- Potassium: 3.5 mmol/l
- Urea: 7.0 mmol/l
- Creatinine: 85 micromoles/l
Next ix?
This sounds like a potential case of lung cancer; the patient may have SIADH as a result (excess ADH released ectopically and inappropriately from the lung tumour). The patient will be euvolaemic. The next thing to do is check plasma and urine osmolality (plasma osmolality low, urine osmolality high). The diagnosis of SIADH:
- No hypovolaemia
- No hypothyroidism
- No adrenal insufficiency
- Reduced plasma osmolality AND increased urine osmolality (>100)
Causes of SIADH include CNS pathology, lung pathology, drugs (SSRI, TCA, opiates, PPIs), tumours and surgery.
A 20-year-old man presents with polyuria and polydipsia. On examination, he has bitemporal hemianopia.
- Sodium: 150 mmol/l
- Potassium: 4.0 mmol/l
- Urea: 5.0 mmol/l
- Creatinine: 70 micromoles/l
Next ix?
This patient has hypernatraemia. Causes of hypernatraemia include unreplaced water loss (GI losses, sweat loss, renal losses e.g. osmotic diuresis, reduced ADH release/action) in association with the patient not being able to control water intake (children, elderly).
Investigations for suspected diabetes insipidus:
- Serum glucose (exclude diabetes mellitus)
- Serum potassium (exclude hypokalaemia)
- Serum calcium (exclude hypercalcaemia)
- Plasma and urine osmolality
- Water deprivation test
A 65-year-old man with type 2 diabetes mellitus and hypertension presents malaise and drowsiness. He is on a basal bolus insulin regimen, ramipril, amlodipine, simvastatin and aspirin.
- Sodium: 125 mmol/l
- Potassium: 6.5 mmol/l
- Urea: 18.0 mmol/l
- Creatinine: 250 micromoles/l
Mx plan?
This patient is hyperkalaemic. They are on ACE inhibitors. The creatinine and urea are also very high, which prompts us to think that the hyperkalaemia is being caused by renal failure (reduced GFR and reduced filtration). We would advise the patient to hold off of Ramipril (less ACE à less aldosterone à less potassium excretion).
A 50-year-old man is referred with hypertension, that has been difficult to control despite maximum doses of amlodipine, ramipril and bisoprolol.
- Sodium: 140 mmol/l
- Potassium: 3.0 mmol/l
- Urea: 4.0 mmol/l
- Creatinine: 70 micromoles/l
Next step?
The hypernatraemia and hypokalaemia prompt us to want to measure the aldosterone:renin ratio.
What is a porphyria?
Group of disorders caused by deficiencies in enzymes of haem biosynthetic pathway
Why is haem vital for erythroid and liver cells?
Creates cytochrome, needed for electron transfer chain in mitochondria
What is one of the key enzymes in the haem synthesis pathway?
ALA synthase (aminolevulinic acid)
Starts of pathway by generated 5-ALA from succinyl CoA + glycine
The rest of the pathway relies on enzymes to change 5-ALA into haem
How may porphyrias be classified?
Site of enzyme deficiency
- erythroid
- hepatic
Clinical presentation
- acute = neurovisceral
- non-acute cutaneous
What causes neurovisceral signs in porphyrias?
Accumulation of 5-ALA
Typically acute presentation
What causes cutaneous signs in porphyrias?
Porphyrin precursors accumulate in skin, become oxidised into porphyrins then into toxic, activated porphyrins by UV light that can cause blistering/non-blistering skin lesions
Porphyrinogens vs porphyrins
Porphyrinogens
- RAISED in porphyria; precursor to porphyrins
- colourless as no double bond
- unstable so will readily oxidise when sample reaches lab
Porphyrins
- highly coloured as double bonds present
- will show up as deep red/purple when urine sample left to oxidise (porphyrinogens -> porphyrins)
Name the acute porphyrias and the enzymes affected
Acute porphyria:
- PBG synthase/ALA dehydratase deficiency
- RARE
Acute intermittent porphyria:
- HMB synthase/PBG deaminase deficiency
Acute porphyrias w skin lesions:
- hereditary coproporphyria (HCP) due to coproporphyrinogen oxidase deficiency
- variegate porphyria (VCP) due to protoporphyrinogen oxidase deficiency
How can you differentiate between the acute prophyrias?
AIP: NO skin lesions
HCP and VP: skin lesions
Send urine sample - PBG raise in ALL three
Check total porphyrins in urine (protect from light) and stool sample
- HIGH in HCP and VP
- not high in AIP
Name the non-acute porphyrias and the enzymes affected
Porphyria cutaenea tarda (most common)
- uroporphyrinogen decarboxylase deficiency
Erythropoietic protoporphyria
- ferrochetelase deficiency
Congenital erythropoietic porphyria
- uroporphyrinogen III synthase deficiency
Which porphyrias are associated with myelodysplastic syndromes?
Erythropoietic porphyria
Congenital erythropoietic porphyria
Which sx are seen in acute porphyrias and in which ones?
Neurovisceral:
- Painful abdomen
- Seizures
- Peripheral neuropathy
- Psychosis
- Port urine
- Muscle weakness
- Constipation
- Urinary incontinence
=> AIP, HCP, VP
Skin lesions:
- blistering
- skin fragility
- affects back of hands and back of neck (sun exposed)
=> HCP, VP
Mx of acute porphyrias
Conservative
- avoid precipitating factors (infection, pre-empt if surgery, ALA synthase inducers)
- adequate nutrition and analgesia
Acute attack
- treat underlying infection/illness
- IV haem arginate
- IV carbohydrate
Which sx are seen in non-acute porphyrias and in which ones?
NO neurovisceral, ONLY skin lesions
PCT
- vesicles on sun-exposed areas
- skin crusting
- superficial scarring and pigmentation
EPP + CEP
- NON-blistering
- photosensitivity; burning, itching, oedema after sun exposure
Mx of non-acute porphyrias
PCT
- avoid precipitants (alcohol, liver disease)
- chloroquine
EPP, CEP
- avoid sun exposure
How do you differentiate between the cutaenous porphyrias?
PCT
- increased urinary uroporphyrins and coproporphyrins
- increased ferritin
- abnormal LFTs
EPP
- RBC protoporphyrin levels elevated
What carcinogen can trigger PCT-like syndrome?
Hexachlorobenzene
What would you expect to see in urine sample if AIP vs PCT?
AIP
- Increased urinary porphobilinogen and aminolaevulinic acid
PCT
- increased urinary uroporphyrins and coproporpyrins
Why may you see hyponatraemia associated with AIP?
Due to SIADH
Which LFTs are indicative of liver cell damage?
ALT AST ALP (alk phos) GGT Bilirubin
Which LFTs are indicative of synthetic function?
Clotting (INR)
Albumin
Glucose
What is the best marker of liver function in acute liver injury?
Prothrombin time
LFT shows ALT and AST > 1000
Ddx?
Acute viral hepatitis
Toxin i.e. paracetamol
Ischaemic hit
What would you suspect with the following LFT findings?
a) AST:ALT 2:1
b) AST:ALT 1:1
c) ALT > AST
d) ALT + AST > 1000
a) EtOH liver disease
b) viral hepatitis
c) chronic liver disease
d) acute viral hep, paracetamol OD, ischaemic hit
What LFTs would you see in a cholestatic/obstructive picture?
Raised GGT and ALP
Why may you see an isolated raised ALP?
Physiological
- pregnancy, childhood
Bone issues
- x5 = Paget’s, osteomalacia
-
Why is ALP normal in myeloma?
Plasma cells suppress osteoblasts
Which conditions may you see low albumin in?
Chronic liver disease Malnutrition Protein-losing enteropathy Nephrotic syndrome Sepsis (3rd spacing)
Which conditions may you see low urea in?
Severe liver disease
Malnutrition
Pregnancy
Which conditions may you see raised urea (x10) in?
Upper GI bleed
Large protein meal
Dehydration
AKI
What clinical findings would you expect to see in prehepatic jaundice?
Normal/increased
- unconjugated bilirubin
- urobilinogen
Normal
- urine colour
- stool colour
- AST/ALT
- ALP
Splenomegaly present
Absent
- conjugated bilirubin
- urine bilirubin
- conjugated bilirubin in urine
What clinical findings would you expect to see in hepatic jaundice?
Increased
- conjugated bilirubin (in urine)
- unconjugated bilirubin
- urobilinogen (in urine)
- AST/ALT
- ALP (could be normal)
Urine colour dark
Stool colour normal/pale
Splenomegaly present
What clinical findings would you expect to see in post-hepatic jaundice?
Increased
- conjugated bilirubin (in urine)
- ALP
- AST/ALT
- urine bilirubin present
Urine colour dark
Stool colour pale
Absent
- splenomegaly
- urobilinogen (or decreased)
Why don’t you get urine bilirubin in prehepatic jaundice?
Uncojugated BR from haem breakdown by macrophages in spleen are tightly bound to albumin thus unable to pass through glomerulus
Why do you get dark urine and pale stools in post-hepatic jaundice?
Increase in urobilinogen/conjugated BR (lots absorbed by blood), pale stool = low levels of stercobilinogen + dark urine
Hepatomegaly with a smooth margin is indicative of which conditions?
Viral hepatitis
Biliary tract obstruction
Hepatic congestion secondary to HF (Budd Chiari)
Hepatomegaly with a craggy border is indicative of which conditions?
Hepatic metastatic disease
Polycystic disease
Cirrhosis (shrinks)
Causes of prehepatic jaundice
- Haemolytic anaemia
- Ineffective erythropoiesis i.e. thalassaemia
- Congestive cardiac failure
Causes of hepatic jaundice
- Hepatocellular dysfunction (viral, alcohol hep)
2. Impaired conjugation, BR excretion, BR uptake (Gilbert syndrome, Crigler Najjar syndrome)
Causes of post-hepatic jaundice
Obstruction of biliary tree
1. Intraluminal (stones, strictures)
- Luminal (mass/neoplasm, inflammation - PSC, PBC)
- Extra-luminal (Ca pancreas, cholangio Ca)
What are common problems in LBW babies?
Respiratory distress syndrome
Retinopathy of prematurity (due to oxygen hypertoxicity)
Intraventricular haemorrhage
Patent ductus arteriosus
Necrotising enterocolitis (inflammation bowel wall - necrosis + perforation)
What is NEC?
Necrotising enterocolitis
- inflammation of bowel wall progressing to necrosis and perforation
- bloody stools
- abdominal distention
- intramural air (pneumatosis intestinalis) on X ray
Compare newborn renal function to adults
Low GFR for surface area
Less reabsorption as short proximal tubule
Reduced concentrating ability as short loops of Henle and distal collecting ducts
Persistent sodium loss due to distal tubule being relatively aldosterone-insensitive
Why do newborns have a high insensible water loss?
High surface area to body weight ratio
Skin blood flow increased
Metabolic/respiratory rate higher than adults
Transepidermal fluid loss (skin not as good barrier/skin not keratinised in prems)
When would you see hypernatraemia in a baby?
Common in first two weeks of term baby/common prems
Associated with dehydration or overly concentrated milk formula
When would you see hyponatraemia in a baby?
Relatively rare
Causes include
- excessive intake > total body water (first 4-5 days life)
- loss of Na loss due to immature tubular function in pts on diuresis (after 4-5 days life)
- factitious (hyperglycaemia)
- congenital adrenal hyperplasia (21-hydroxylase deficiency)
Clinical features of congenital adrenal hyperplasia when presenting as a child
Hyponatraemia/hyperkalaemia with volume depletion
Hypoglycaemia (lack of cortisol)
Ambiguous genitalia in perceived female neonates
- believed male neonates more likely to present w salt-losing crisis
Growth acceleration due to excess androgens (rare complaint in children)
What presentation of jaundice is always pathological in a neonate?
Jaundice <24 hours of life
- acute haemolysis
- sepsis
Jaundice > 2 weeks of life
- hepatobiliary failure
Conjugated hyperbilirubinemia at any stage of infancy
- biliary atresia
- ascending cholangitis in TPN
Typical changes seen in hepatic markers due to pre hepatic jaundice
Unconjugated BR: ++ Conjugated BR: normal ALT/AST: normal ALP: normal/++ GGT: normal/++
Typical changes seen in hepatic markers due to hepatic jaundice
Unconjugated BR: normal Conjugated BR: ++ ALT/AST: ++ ALP: + GGT: +
Typical changes seen in hepatic markers due to post hepatic jaundice
Unconjugated BR: normal Conjugated BR: ++ ALT/AST: + ALP: ++ GGT: ++
Fat soluble vitamins
A, D, E, K
Water soluble vitamins
B1, B2, B3, B6, B12, C, folate
Vit A deficiency results in
Colour blindness
Vit A excess results in
Exfoliation
Hepatitis
Vit D deficiency results in
Osteomalacia
Rickets
Vit D excess results in
Hypercalcaemia
Vit E deficiency results in
Anaemia/neuropathy
?Malignancy/IHD
Vit K deficiency results in
Defective clotting
How do you test for fat soluble vitamin levels?
A, D, E = serum
K = PTT
What are the other names for the following vitamins?
a) B1
b) B2
c) B3
d) B6
e) B12
a) thiamine
b) riboflavin
c) niacin
d) pyridoxine
e) cobalamin
B1 deficiency results in
Beri-beri
Neuropathy
Wernicke’s
B2 deficiency results in
Glossitis
B3 deficiency results in
Pellagra (3Ds)
- dementia
- dermatitis
- diarrhoea
B6 deficiency result sin
Dermatitis
Anaemia
B12 deficiency results in
Pernicious anaemia
B6 excess results in
Neuropathy
Vit C deficiency results in
Scurvy
Vit C excess results in
Renal stones
Folate deficiency results in
Megaloblastic anaemia
Neural tube defects
How do you test for water soluble vitamin levels?
B1 = RBC transketolase B2 = RBC glutathione reductase B6 = RBC AST activation B12 = serum B12 Vit C = plasma levels Folate = RBC folate
Iron deficiency results in
Hypochromic anaemia
Iodine deficiency results in
Goitre
Hypothyroidism
Zinc deficiency results in
Dermatitis
Copper deficiency results in
Anaemia
Fluoride deficiency results in
Dental caries
Copper excess results in
Wilson’s disease
Fluoride excess results in
Fluorosis
What are caeruloplasmin levels in Wilson’s disease?
Low
- caeruloplasmin is a copper-binding protein so all used up in Wilson’s
What deficiencies are seen in Crohn’s?
ADEK
B12
Foalte
Calcium, phosphate, magnesium, zinc deranged if high output/chronic diarrhoea
What deficiencies are seen in coeliac?
Iron
ADEK
B1
B6
What deficiencies are seen in chronic liver disease?
ADEK B12 Selenium Magnesium Zinc Folate
What is seen in chronic kidney disease?
Protein energy wasting syndrome
What deficiencies are seen in pancreatic insufficiency?
ADEK
Causes of hyperinsulinaemic hypoglycaemia
Insulin overdose
Sulfonylurea excess
Insulinoma
Anorexia nervosa
Causes of hypoinsulinaemic hypoglycaemia with +ve ketones
Alcohol binge with no food Pituitary insufficiency Addison's Liver failure Anorexia nervosa
Causes of hypoinsulinaemic hypoglycaemia with -ve ketones
Non pancreatic neoplasms
- fibrosarcomata
- fibromata
Triad of hypoglycaemia
Low glucose (varies for different patient populations)
Symptoms (adrenergic, neuroglycopenic, but could be no symptoms)
Relief of symptoms on administration of glucose
Sx seen in hypoglycaemia
Adrenergic: tremors, palpitations, sweating, hunger
Neuroglycopaenic: somnolence, confusion, incoordination, seizures, coma
Asymptomatic in individuals who have frequent hypos
Hyperglycaemic hypoglycaemic with low C-peptide
What is this a result of?
Exogenous insulin overdose
- patient education to ensure correct insulin delivery method
- may have been intentional so consider psych review
What is seen in non-islet tumour hypoglycaemia?
Low glucose, insulin, C-peptide, FFA and ketones
Result of paraneoplastic syndrome secreting IGF-2, binding to IGF-1 and insulin receptor
Drugs that cause hypoglycaemia
Oral hypoglycaemics
- sulphonylureas
- GLP-1 agents
Insulin
Other drugs
- beta-blockers
- salicylates
- alcohol (inhibits lipolysis)
Calicum range
2.2-2.6 mmol/l
Which two hormones are involved with calcium metabolism?
PTH
Calcitriol (1, 24 (OH)2D)
What does PTH do?
Increases tubular 1-alpha hydroxylation of vit D (25(OH)D)
Mobilises calcium from bone
Increases renal calcium reabsorption
Increases renal phosphate excretion (phosphate trashing hormone)
What does calcitriol do?
Increases calcium and phosphate absorption from the gut
Bone remodelling
Primary hyperparathyroidism causes
Parathyroid nodule (80%)
Hyperplasia and multiple adenomas (15%)
Carcinomas (0.5%)
MEN1 and MEN2
Secondary hyperparathryoidism causes
CKD
Vit D deficiency
Tertiary hyperparathryoidism causes
Prolonged secondary hyperPTHism causing unregulat secretion of PTH
Kidney transplant
Hypoparathyroidism causes
Postsurgical (most common) Postradiation Autoimmune Iron deposition in people with thalassaemia Hypo/hypermagnaseamia PseduohypoPTH (resistant to PTH) DiGeorge Syndrome
Calcium: high Phosphate: low PTH: high/normal ALP: high/normal Vit D: normal
Dx?
Primary hyperparathyroidism
=> intrinsic problem with parathyroid gland causing increased PTH
Calcium: low/normal Phosphate: high PTH: high ALP: high Vit D: normal
Dx?
Secondary hyperparathyroidism
=> stimulation of parathyroid gland to produce more PTH
Calcium: high Phosphate: low PTH: high/normal ALP: high/normal Vit D: normal
Dx?
Tertiary hyperparathyroidism
=> autonomous PTH secretion
Calcium: low Phosphate: high PTH: low ALP: low/normal Vit D: normal
Dx?
Hypoparathyroidism
Calcium: low Phosphate: low PTH: high ALP: high Vit D: low
Dx?
Osteomalacia/Ricket’s in children
Calcium: normal Phosphate: normal PTH: normal ALP: high Vit D: normal
Dx?
Paget’s disease
=> re-modelling of bone, very rare
Calcium: normal Phosphate: normal PTH: normal ALP: normal Vit D: normal
Dx if pt has bone pain?
Osteoporosis
=> bone loss as result of wear and tear
Risk factors for Vit D deficiency
Lack of sunlight
Dark skin
Dietary changes
Gut malabsorption (i.e. coeliac)
Hypercalcaemia definition
> /= 2.6 mmol/L
Hypercalcaemia sx
Stones (renal)
Bones (pain)
Groans (psych)
Moans (abdo pain)
- constipation
Polyuria
- it is an osmotic diuretic
Neuro
- muscle weakness
- confusion
- seizures
- coma
Hypercalcaemia treatment
Double check it is genuine result (repeat if in doubt)
Rehydrate, fluids!
Bisphosphonates IV
- zolendronic acid
- pamidronate
Treat the underlying cause (check PTH levels)
Causes of hypercalcaemia
Dehydration Hyperparathyroidism Cancer Sarcoidosis Milk alkali syndrome Thyrotoxicosis Hypervitaminosis D
What can PTH tell us about the cause of hypercalcaemia?
Appropriate response
- PTH suppressed
- malignancy most likely
- sarcoid, vit D excess, thyrotoxicosis, milk alkali syndrome
Inappropriate response
- PTH not suppressed (raised/normal)
- primary hyperparathyroidism most likely
- familial hypocalciuric hypercalcaemia (rare)
Hypocalcaemia sx
Increased reflexes
Stridor
Perioral paraesthesia
Chvostek’s sign (twitching when you tap face)
Trousseau’s sign (carpopedal spasm with BP cuff)
Why does malignancy result in hypercalcaemia?
Ectopic PTH-related peptide released by tumour
- squamous cell lung cancer
Bone mets resulting in local bone osteolysis
- breast cancer
Haematological malignancy releases cytokines causing bone breakdown
- myeloma
Hypocalcaemia treatment
Repeat result and adjust for albumin (corrected calcium) to confirm if unsure
Symptomatic or Ca2+ < 1.875 mmol/L
-> 10% calcium gluconate IV
Asx/chronic/milk
- Oral calcium supplementation (not at mealtime); SandoCal
- vit D if low PTH or vit D
Hypocalcaemia causes with high phosphate
High phosphate
- CKD
- hypoparathyroidism
- post thyroid surgery
- pseudohypoparathyroidism
- hypomagnesaemia
Hypocalcaemia misreading due to
Artefact
- hypoalbuminaemia
Hypocalcaemia causes with low phosphate
Low phosphate
- osteomalacia
- acute pancreatitis
- overhydration
- respiratory alkalosis (decreased ionised/active Ca2+)
Risk factors for renal stones
Dehydration
Abnormal urine pH (meat intake, renal tubular acidosis)
Increased excretion of stone constituents
Urine infection
Anatomical abnormalities
Renal stones that are radio-opaque
Calcium mixed
Calcium oxalate
Calcium phosphate
Triple phosphate “Struvite” (staghorn appearance)
Renal stones that are radiolucent
Uric acid
Cysteine
Preventative mx of renal stones
Good hydration Reduce oxalate intake Maintain normal Ca intake Thiazide-induced hypocalciuria Citrate to alkalinise urine
Ix for recurrent renal stones
Serum: Cr, bicarb, Ca, phosphate, urate, PTH
Stone analysis
Spot urine: pH, MCS, amino acids, albumin
24 hr urine: volumte (>2.5l), Ca, oxalate, urate, citrate
Best measure of kidney function
Glomerular filtration rate
= 120ml/hr
= age-related decline approx. 1ml/hr/yr
What does the presence of proteinuria on dipstick suggest?
Abnormal excretion of protein (usually albumin) due to leaky glomeruli or inability of tubules to reabsorb protein
What are the key differences between AKI and CKD?
AKI
- abrupt decline in GFR
- potentially reversible
- treatment targeted to precise diagnosis and reversal of disease
CKD
- longstanding decline in GFR
- irreversible
- treatment targeted to prevention of complications of CKD and limitation of progression
What do we measure to assess severity of an AKI?
Serum creatinine
Urine output
What makes a good marker for GFR?
Clearance of marker = GFR if:
- not bound to serum proteins
- freely filtered by glomerulus
- not secreted/reabsorbed by tubular cells
What GFR marker do we use in clinical practice?
Creatinine
- endogenous marker
- higher in muscular individuals as by-product of muscle turnover
- important to know baseline to FOLLOW TREND
Define AKI
- Rise in serum Cr over 26 within 48 hours
- 50% or greater rise in serum Cr known or presumed to have occurred within the past 7 days
- Fall in urine output to less than 0.5ml/kg/hour for more than 6 hours
Indications for emergency dialysis
A E I O U
- Acidosis
- Electrolyte disturbance (refractory hyperkalaemia)
- Intoxication (lithium, aspirin)
- Overload (pulmonary oedema)
- Uraemic encephalopathy
CKD Staging
Stage 1
- kidney damage with normal GFR (90+)
Stage 2
- Mild GFR (60-89)
Stage 3
- Moderate GFR (30-59)
Stage 4
- Severe GFR (15-29)
Stage 5
- End-stage kidney failure (< 15/dialysis)
Common causes of CKD
Diabetes Atherosclerotic renal disease Hypertension Chronic glomerulonephritis Infective or obstructive uropathy Polycystic kidney disease
Complications of CDK
Failing homeostatic function
- acidosis, hyperkalaemia
Failing hormonal function
- anaemia (no EPO), renal bone disease (low vit D)
CVD
- vascular calcification, uraemic cardiomyopathy
Uraemia and death
How is haemodialysis done?
Tunneled central line (Tessio line)
OR
Arteriovenous fistula
How is peritoneal dialysis done?
Via a Tenckoff catherer where peritoneum used as dialysis membrane
Aldosterone action
Sodium IN
Potassium OUT
What do the following hypothalamic hormones trigger production of in the pituitary?
a) GHRH
b) GnRH
c) TRH
d) Dopamine
e) CRH
a) GH
b) LH/FSH
c) TSH, prolactin
d) Prolactin
e) ACTH
* remember this is hypothalamo-pituitary axis
Contraindications of combined pituitary function test
Ischaemic heart disease
Epilepsy
Untreated hypothyroidism (impairs GH and cortisol response)
Side effects of combined pituitary function test
Adrenergic effects of hypoglycaemia
- sweating, palpitations, LOC. convulsions (RARE)
Metallic taste in mouth, flushing and nausea
What is in combined pituitary function test?
LHRH (GnRH), TRH and insulin
Pituitary tumour classifications
Microadenoma < 10mm (usually benign)
Macroadenoma > 10mm (aggressive bb)
Non-functioning adenoma (crushes stalk…)
What visual changes may you see with a pituitary adenoma?
Bitemporal hemianopia due to optic chiasm compression
Macroprolactinaemia
> 5000 miu/l prolactin lol
Mx of prolactinoma
1st line:
Replacement
- hydrocortisone, T4, oestrogen, GH
- DA antagonists (cabergoline, bromocriptine)
2nd line:
Transphenoidal excision
Mx of non-functioning pituitary adenoma
Cabergoline/bromocriptine
- watch and wait if asx
- if no sx just leave it alone bb
Diagnosis of acromegaly
OGTT (gold standard)
IGF-1
Signs: high glucose, Ca, phosphate
Mx of acromegaly
- Transphenoidal surgery
- Pituitary radiotherapy if surgery fails
- Cabergoline
- Octreotide - somatostatin analogue (expensive bad boi and cannot stop once started)
- GH antagonist - pegvisomant
High TSH
Low T4
Diagnosis?
Hypothyroidism
- atrophic
- Hashimoto’s
- subacute (De Quervain’s)
- postparum
- Riedal thyroiditis
High TSH
Normal T4
Diagnosis?
Treated hypothyroidism or subclinical hypothyroidism
- look out for associated hypercholesterolaemia seen in hypothyroid pts
High TSH
High T4
Diagnosis?
TSH secreting tumour
Thyroid hormone resistance
Low TSH
High T4/3
Diagnosis?
Hyperthyroidism
- Grave’s
- toxic multinodular goitre (Plummer’s)
- toxic adenoma
- drugs (thyroxine, amiodarone)
- ectopic (trophoblastic tumour, struma ovarii)
Low TSH
Normal T4/3
Diagnosis?
Subclinical hyperthyroidism
- may progress to 1o hypothyroidism if pt is anti-TPO antibody +ve
Low TSH
Low T4
Diagnosis?
Secondary hypothyroidism
- hypothalamic/pituitary disorder
High TSH followed by low TSH
Low T3/4
Diagnosis?
Sick euthyroidism with any severe illness
- body shuts down metabolism as thyroid gland reduced output
Normal TSH
Abnormal T4
Diagnosis?
?Assay interference
Changes in TBG
Amiodarone
Hyperthyroid tx
Sx relief
- beta blockers
- topical steroids for dermopathy
- eye drops in Graves
Medical
- carbimazole (agranulocytosis risk, rashes common)
Radio-iodine
- risk of permanent hypothyroidism
- CI in pregnancy and lactating women
Surgical
- hemi/total thyroidectomy
Indications for surgical thyroidectomy
Women intending to become pregnant in next 6/12
Local compression 2o to thyroid goitre (oesophageal/tracheal)
Cosmetic
Suspected cancer
Co-existing hyperparathyroidism
Refractory to medical tx
Thyroid storm tx
HDU/ITU support Cooling required High dose anty-thyroid medication Corticosteroids Circulatory and respiratory support
How could a pt present in thyroid storm?
Shock
Pyrexia
Confusion
Vomiting
anti-TSH receptor abs
Which thyroid problem?
Graves disease
- hyper, high uptake on isotope (Tc99)
anti-TPO/TG abs
Which thyroid problem?
Hashimotos thyroiditis
Hurthle cells
What’s wrong with thyroid?
Hashimotos thyroiditis
Higher risk of thyroid neoplasm
Solitary Solid Young Male Cold nodules
Psammoma bodies and empty-appearing nuclei with central clearing
Which thyroid neoplasia?
Papillary
- women
- associated with irradiation
- good prognosis
empty nuclei = Orphan Annie eyes
What do follicular thyroid neoplasias spread to first?
Blood»_space; lungs, bone, liver, breast, adrenals
Parafollicular C cells secreting calcitonin
Which thyroid neoplasia?
Medullary
- sporadic 80%, MEN2 20% cases
What should you screen for with medullary thyroid neoplasia?
Phaeochromocytoma
- MEN2 mutation
What is MALToma associated with?
Chronic Hashimoto’s
Undifferentiated follicular, large pleomorphic giant cells with spindle cells
Which thyroid neoplasia?
Anaplastic
- elderly
- die within a year :(
MEN1 disorders
Pituitary
Pancreatic (insulinoma)
Parathyroid (hyper)
*3Ps
MEN2a disorders
Parathyroid
Phaeochromocytoma
Medullary thyroid
*2Ps, 1M
MEN2b disorders
Phaeochromocytoma
Medullary thyroid
Mucocutaneous neuromas (& marfanoid)
*1P, 2Ms
High K+ Low Na+ Low glucose 90/50 BP upon standing Skin pigmentation noted in mouth
What ix would confirm diagnosis?
SynACTHen test
- Addison’s
High K+ Low Na+ Low glucose 90/50 BP upon standing Skin pigmentation noted in mouth
What tx needed?
Hydrocortisone and fludrocortisone if primary adrenal lesion present
- Addison’s
Ix for Cushing’s
Overnight dexamethasone suppression test
OR
24hr urinary free cortisol
Ideal now is inferior pituitary petrosal sinus sampling however not always available
ACTH dependent Cushing’s
Pituitary tumour (Cushing's disease x) Ectopic ACTH-producing tumour (small cell Ca, carcinoid tumour)
ACTH independent Cushing’s
Adrenal adenoma/cancer
Adrenal nodular hyperplasia
Iatrogenic steroid use lol
Low K+
High Na+
156/100 BP not responding to tx
What ix would confirm diagnosis?
Aldosterone:renin ratio
- RAISED in Conn’s
Low K+
High Na+
156/100 BP not responding to tx
What tx needed?
Aldosterone antagonists/K+ sparing diuretics for Conn’s
- spironolactone
- eplerenone
- amiloride
Phaeo tx
- Alpha blockade
- Beta blockade
- Surgery when BP well controlled
Phaeo ix
Plasma and 24h urinary metadrenaline measurement/catecholamines & VMA (metabolite of adrenaline)
Phenytoin toxicity
Ataxia
Nystagmus
Digoxin toxicity
Arrhythmias
Heart block
Confusion
Xanthopsia
Lithium toxicity
Tremor (early) Lethargy Fits Arrhythmia Renal failure
Aminoglycosides toxicity
Tinnitus
Deafness
Nystagmus
Renal failure
Theophylline and aminophylline toxicity
Arrhythmias
Convulsions
Anxiety
Tremor
Which enzymes are raised in acute pancreatitis?
Amylase (>10x upper limit normal)
Lipase (>3 upper reference)
Pathological raised levels of CK
Duchenne Muscular Dystrophy
Myocardial infarction
Rhabdomyolysis
Statin related myopathy
How do we differentiate ALP raised due to bone of liver problems?
We can differentiate liver from bone ALP either by seeing if there is a rise in gamma-GT (liver ALP
rises with this), by performing electrophoresis, or by ordering a bone-specific assay of ALP
Physiological causes of raised ALP
Pregnancy (3rd trimester)
Childhood (during growth spurt)
Pathological causes of raised ALP
> 5x ULN
- Bone = Paget’s, osteomalacia
- Liver = cholestasis, cirrhosis
<5x ULN
- Bone = tumours, fractures, osteomyelitis
- Liver = infiltrative disease, hepatitis
When is BNP released?
In response to ventricular stretch
Highly sensitive for heart failure when levels > 400
Highly specific for excluding HF when levels < 100
What is troponin?
Myocardial injury biomarker
NOT an enzyme b
When is troponin measured for MI?
Measure at 6 hours then 12 hours post onset of pain
Remains elevated for 3-10 days
When is troponin raised?
Coronary spasm Coronary dissection PCI Myocarditis PE HF Cardiomyopathies Sepsis Cardiac surgery Chest trauma Defibrillation
Types of lipoprotein metabolism disorders
Primary hypercholesteraemia
Primary hypertriglyceridaemia
Primary mixed hyperlipidaemia
Hypolipidaemia
How do statins work?
HMG-CoA reductase inhibitor
- reduces intrinsic synthesis of cholesterol in lover
- SE: myopathy, rhabdomyolysis, fatigue
Lipoproteins in order of density
Chylomicron < FFA < VLDL < IDL < LDL < HDL
What does Guthrie blood spot test for at 6 days of age?
Phenylketonuria, congenital hypothyroidism, cystic fibrosis, sickle cell disease, MCAD (medium
chain acylCoA dehydrogenase) deficiency
*The newborn screening programme measures chemicals in the blood spot, it doesn’t
involve any genetics. An abnormal chemical level doesn’t always mean that there is a
genetic disorder!
What does specificity mean?
Probability that someone without the disease will correctly test negative
o TN/(FP+TN)
o 85 people without CF in total, and 80 actually test negative. Specificity is 80/85=94%
What does sensitivity mean?
Probability that someone with the disease will correctly test positive
o TP/(TP+FN)
o 100 people with CF in total, and 90 actually test positive. Sensitivity is 90/100=90%
What does positive predictive value mean?
Probability that someone who tests positive actually has the disease
o TP/(TP+FP)
o 95 people tested positive, of which 90 had the disease. PPV=90/95=95%
What does negative predictive value mean?
Probability that someone who tests negative actually doesn’t have the disease
o TN/(TN+FN)
o 90 people tested negative, of which 80 didn’t have the disease, NPV=80/90=89%
Metabolic conditions that result in accumulation of toxins
Organic acidaemias
- propionic acideamia
Urea cycle disorders
Aminoacidopathies
- PKU
- Maple syrup urine disease
Metabolic conditions that result in reduced energy stores
Glycogen storage disorders
- Von Gierke;s
Galactossaemia
Fatty acid oxidation disorders
- MCADD
Metabolic conditions that result in large molecule synthethesis
Peroxisomal disorders
Glycosylation disorders
Metabolic conditions that result in defects in large molecule metabolism
Lysosomal disorders
- Tay Sachs disease
Metabolic conditions that affect the mitochondria
MELAS
Kearn’s
Sayre
POEMS
Diabetes mellitus type 2 diagnosis
HbA1C >48
Fasting glucose >7
Random glucose >11.1
IGTT >11.1
IGTT > 7.8 but < 11.1
Diagnosis?
Impaired glucose tolerance
Fasting glucose > 6.1 but < 7.0
Diagnosis?
Impaired fasting glucose
DKA criteria
pH < 7.3, Plasma Glucose >11mM, Blood Ketones>3mM (2+ in urine).
Rapid onset
Medical emergency
DKA presentation
Symptoms: confusion, Kussmaul breathing, abdominal pain, nausea, vomiting
Precipitants include infection, surgery, missed insulin doses, trauma
DKA mx
A-E, senior help
Fluid = 0.9% saline
Insulin = AFTER fluids, ensure K+ fine, 0.1u/kg/h fixed rate
Early senior review +/- ITU involvement
Monitor glucose and K+ hourly
Catheter to monitor UO
HHS criteria
pH > 7.3, Osmolarity > 320mOsm, Blood Glucose > 30mM
HHS develops over few days
Patients present acutely unwell with confusion and clinical dehydration
HHS mx
A-E
Fluids = 0.9% saline over 1hr
IV insulin = only if > 1 mmol/L ketones, 0.05u/kg/hr fixed rate
Monitor = serial U&Es, glucose reading
When is DKA resolved?
When ketones < 0.6 and pH > 7.3
Causes of a raised anion gap metabolic acidosis
G: Glycols (ethylene glycol and propylene glycol) [overdose]
O: Oxoproline [chronic paracetamol use, usually malnourished women]
L: L-lactate [sepsis]
D: D-lactate [short bowel syndrome]
M: Methanol [overdose]
A: Aspirin [overdose. Initially causes respiratory alkalosis but in moderate/severe overdose causes metabolic acidosis]
R: Renal failure
K: Ketoacidosis [DKA, alcoholic, starvation
Causes of a normal anion gap metabolic acidosis
Addison’s disease
Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis)
Chloride gain (Sodium Chloride 0.9% infusion)
Drugs (acetazolamide)
An unexplained metabolic acidosis (usually in the context of overdose) with a raised anion and raised osmolar gap could be caused by?
Glycol, ethanol, mannitol or methanol poisoning
