Chem

Question 1

SUMMARY CARD:

All relevant equations in Chem Path:
1. Osmolarity
2. Osmolar gap
3. Anion gap

Answer 1

1. Osmolarity = 2(Na + K) + urea + glucose
2. Osmolar gap = osmolality (measured) - osmolarity (calculated) (if < 10, then normal)
3. Anion gap = (Na + K) - (Cl + HCO3) (normal range = 14-18)

Question 2

SUMMARY CARD:

• Where is fluid found in the body?
• What is osmolality vs osmolarity?
• BONUS: which ion is the largest contributor to osmolality?

Answer 2

• 60-40-20 rule = 60% of total body weight is water (40% is intracellular, 20% extra cellular)
• Osmolality = total number of particles in a solution measured with an osmometer; units are mmol/kg (AKA the mass of a solvent); normal range for serum osmolality is 275-279 mmol/kg
• OsmolaRity = the volume in litRes of the solvement; units are mOsm/L

Omolality is more accurate, but osmolarity is easier to calculate!

NOTE: osmolality is more accurate because it uses mass of the solvent, which always stay the same, whereas volume expands with increasing temperatures

• BONUS: Na+ is the biggest contributor to plasma osmolality

Question 3

SUMMARY CARD:

Fluid balance equations:
1. Osmolarity equation
2. Osmolar gap equation
3. What does it mean to have a raised osmolar gap?

Answer 3

1. Osmolarity = 2(Na + K) + urea + glucose
2. Osmolality - osmolarity = < 10 (NORMAL)

If the osmolar gap is > 10, then there are other unmeasured ions in the sample –> SKALP:

• Sugar: mannitol, sorbitol
• Ketones
• Alcohol: methanol, ethanol
• Lipids (↑ triglycerides) / Lactate
• Proteins: ↑ gammaglobulinaemia

Question 4

SUMMARY CARD:

• What is the normal range for plasma [Na+]?
• How is Na+ regulated?

Answer 4

135-145 mmol/L

TWO ways to regulate Na+:

1. Blood volume: ↑ blood volume = atrial stretch = ANP (atrial natriuretic peptide) release = ↓ aldosterone release + ADH + renin = ↓ [Na+] in blood

2. Blood osmolality: ↑ blood osmolality = ↑ thirst + ADH release = ↓ [Na+] in blood

Question 5

SUMMARY CARD:

• What is mild vs severe hyponatraemia?
• What are the Sx of hyponatraemia?
• How do you define true vs pseudohyponatraemia and what are possible causes of each?

Answer 5

• Mild hyponatraemia = 130-135 mmol/L; severe = < 125 mmol/L
• Sx = N&V, confusion, muscle weakness/cramps, seizures, coma
• Mx with IV 0.9% NaCl ONLY if symptomatic (or v. severe) hyponatraemia

Use OSMOLALITY to determine true vs pseudohyponatraemia

If LOW plasma osmolality, then TRUE hyponatraemia:

• Assess volume status w/ clinical exam (e.g. BP, HR, oedema, cap refill) AND check urinary Na+ for cause
• Hypovolaemic + urinary Na+ < 20 mmol/L = extra-renal causes e.g. D&V, burns, TURP syndrome (hypotonic irrigation absorbed through damaged prostate)
• Hypovolaemic + urinary Na+ > 20 mmol/L = renal loss e.g. AKI/CKD, diuretics, Addison’s (can also be eu)
• Euvolaemic = psychogenic polydipsia, SIADH, Addison’s (can also be hypo)
• Hypervolaemic + urinary Na+ < 20 mmol/L = extra-renal e.g. HF, cirrhosis, nephrotic syndrome
• Hypervolaemic + urinary Na+ > 20 mmol/L = renal failure

If NORMAL or HIGH plasma osmolality, then PSEUDO hyponatraemia:

• May be caused by the sample coming from an arm with a drip in it OR due to other unmeasured ions e.g. mannitol, glucose (HHS) OR post-surgery (e.g. over hydration w/ IV fluids, or ↑ ADH release due to stress of the surgery)

Question 6

SUMMARY CARD:

What are the steps to assessing the cause of hyponatraemia?

Answer 6

• Step 1: assess plasma osmolality (true vs pseudo)
• Step 2: assess volume status
• Step 3: measure urinary sodium (extra-renal vs renal causes)

Question 7

SUMMARY CARD:

What is the management for each of these?

Answer 7

• If HYPOvoloaemic hyponatraemia: regardless of renal or extra-renal cause, Mx with IV 0.9% NaCl if symptomatic (or v. severe) hyponatraemia

If EUVOlaemic hyponatraemia:

• Psychogenic polydipsia: if acute + symptomatic hyponatraemia = IV 0.9% saline; if chronic = fluid restriction + CBT (can consider furosemide)
• Chronic hypothyroidism = levothyroxine
• Addison’s (AKA adrenal insufficiency) = Hydrocortisone (glucocorticoid) +/- fludrocortisone (mineralocorticoid)
• SIADH = demecocycline (check renal function first as it can cause NDI) OR tolvaptan
• If HYPERvolaemic hyponatraemia: fluid restrict +/- diuresis (unless due to cirrhosis, then requires specialist input)

Question 8

SUMMARY CARD:

For SIADH, what is / are the:

1. Diagnostic criteria?
2. Causes?
3. Mx?

Answer 8

1. Diagnostic criteria = diagnosis of exclusion so NO adrenal/ thyroid / renal dysfunction, AND:

TRUE hyponatraemia (< 135) + LOW plasma osmolality + HIGH urine sodium (>20) + HIGH urine osmolality (>100)

SIADH = syndrome of inappropriate ADH secretion (not in response to a stimulus), which results in less water excreted in the urine

Ix require normal 9am cortisol, short synATCHen test and TFTs (as this is a diagnosis of exclusion)

2. Causes = Lung, Brain, Drugs:

• Malignancy (ectopic ADH secretion): SCLC, pancreas, prostate, lymphoma
• CNS disorders: infection, haemorrhage
• Lungs: TB, pneumonia
• Drugs: opiates, SSRIs, TCAs, carbamazepine, PPIs

3. Mx = acute vs chronic:

• Acute: fluid restriction, if severe IV hypertonic saline +/- furosemide
• Chronic: fluid restrict to 1L per day, demecocycline (check renal function first as it can cause NDI) or tolvaptan

Question 9

SUMMARY CARD:

Why does cirrhosis cause hypervolaemic hyponatraemia?

BONUS: why does HF cause hypervolaemic hyponatraemia?

Due

Answer 9

Due to poor breakdown of vasodilators e.g. nitric oxide in the liver = ↓ BP = subsequent ↑ ADH release = ↑ water retention

BONUS: similar reason to cirrhosis –> ↓ cardiac output = subsequent ↑ ADH release = ↑ water retention

Question 10

SUMMARY CARD:

What happens if Na+ is corrected too quickly (+Sx)?

What is the ideal rate of Na+ correction?

Answer 10

Central pontine myelinolysis

RF = malnourished alcoholic

• Pseudobulbar palsy = indistinct speech, drooling, dysphagia, spastic tongue, brisk jaw jerk, dysarthria
• Paraperesis = partial inability to move
• Locked-in syndrome = body paralysis but consciousness and ability to move eyes are preserved

Ideally: do NOT increase Na+ by more than 8-10 mmol/L per 24hrs

Question 11

DISEASE:

A patient is getting IV NaCl rehydration in their R arm following a night of binge drinking
They are currently asymptomatic

Their blood test shows Na+ of 123 mmol/L but high osmolality

Identify a possible cause of this result?

hint: nurse took blood from R arm

Answer 11

Low Na+ and ↑ osmolality = PSEUDOhyponatraemia

Sample was taken from drip arm –> caused dilution of the Na+

Question 12

DISEASE:

28F - abdo pain + confusion + kussmaul breathing
PMH = T1DM
Ix = incidental hyponatraemia finding

What is a possible cause of this?

Answer 12

Pt is presenting w/ DKA = ↑ ketones –> lowers water potential of blood = high osmolality, therefore it appears they have hyponatraemia (AKA pseudohyponatraemia)

Question 13

DISEASE:

Post-surgical pt complains of N&V + cramping in his legs
He was given IV fluids during his surgery
Ix = Na+ of 122 mmol/L

Identify a possible cause of this result?
(BONUS: Mx?)

Answer 13

(Hypervolaemic) hyponatraemia (AKA pseudohypoatraemia) can occur post surgery due to overhydration with IV fluid during the surgery

As the pt is symptomatic with severe hyponatraemia (< 125), Mx = IV 3% NaCl (hypertonic) + furosemide

Question 14

DISEASE:

35M = extensive burns following a workplace accident
He complains of weakness and confusion

Ix = hyponatremia w/ Na+ 125 mmol/L

What type of hyponatraemia is this?
(Bonus: Mx for ↓Na+?)

Answer 14

Hypovolaemic hyponatraemia due to fluid loss via burns

Mx = fluid replacement w/ IV NaCl

Question 15

DISEASE:

65M - underwent transurethral resection of the prostate for BPH

Post-op, he develops hyponatremia (Na+ 128 mmol/L)

What is this syndrome called and why does it occur?

Answer 15

TURP (transurethral resection of the prostate) syndrome

Fluids absorbed during irrigation in TURP through damaged prostate = hyponatraemia

Question 16

DISEASE:

26F - 5kg weight loss, muscle weakness, hyperpigmented palms of hands
Does not appear clinically dehydrated

U&Es = ↓Na+, ↑K+

1. Diagnosis?
2. Ix?
3. Mx?
4. BONUS: how is an addisonian crisis managed?

Answer 16

1. Addison's disease (AKA adrenal insufficiency) –> causes hypo/eu volaemic hyponatraemia due to lack of aldosterone release
2. Ix:

• 9AM cortisol = low
• Short synACTHen test –> serum cortisol fails to double at 30 mins indicates adrenal failure (normal = sufficient increase in cortisol)

3. Long-term Mx = replacement of glucocorticoids with hydrocortisone (3x/day) and mineralocorticoids with fludrocortisone

BONUS:

• Addisonian crisis = hypotensive shock, usually precipitated by infection / surgery
• MEDICAL EMERGENCY –> Mx = rapid IV fluid rehydration w/ 1l 0.9% normal saline over 1 hour + 50 mL of 5% dextrose to correct hypoglycaemia + IV/IM 200 mg hydrocortisone bolus + Tx of underlying cause

Question 17

DISEASE:

60M - ascites + lower limb oedema
PMH - alcohol misuse

Bloods: ↑elevated liver enzymes, ↓Na+

What is this type of hyponatraemia?
BONUS: what is the cause?

Answer 17

Hypervolaemic hyponatraemia due to cirrhosis / liver failure

Liver fails to break down vasodilators e.g. NO = ↓BP = ↑ ADH release = hypervolaemic hyponatraemia

Question 18

DISEASE:

55M - severe D&V following street food/takeaway –> given IV NaCl
Now: quadriparesis, indistinct speech, dysphagia
PMH: poor diet + alcohol misuse

What is the diagnosis?
What are the RFs?

Answer 18

Central pontine myelinolysis due to rapid correction of Na+

Sx = pseudobulbar palsy (indistinct speech, dysphagia), paresis, etc.

RFs = malnourished alcoholics

Question 19

DISEASE:

70F - brought in by LAS from carehome following 2 hours of muscle weakness and confusion
No FLAWS

Ix = Na+ 126 mmol/L and plasma osmolality < 100

What is the diagnosis?
BONUS: Mx?

HINT: euvolaemic hyponatraemia

Answer 19

Psychogenic polydipsia = euvolaemic hyponatraemia

RFs = carehome, elderly pt

Acute Mx = IV 0.9% saline as pt is symptomatic
Chronic MX = fluid restriction

Question 20

DISEASE:

57M - cough + crackles in R lung bases
Tachycardic, temp 38.8°C

Ix = low Na+, normal urea

What is the cause of the low Na+?

Answer 20

SIADH - can be caused by pneumonia

Question 21

SUMMARY CARD:

• What is mild vs clinically significant hypernatraemia?
• What are the Sx of hypernatraemia?

Answer 21

• Hypernatraemia is Na+ >145 mmol/L; it is clinically significant if Na+ > 148 mmol/L
• Sx = thirst, confusion, irritability, ataxia + seizures, coma

Question 22

SUMMARY CARD:

What are the steps to identifying the cause of hypernatraemia?

Answer 22

Assess volume status, then assess urinary Na+

1. HYPOvolaemic hypernatraemia + LOW urinary Na+: GI losses (D&V if water>electrolytes lost), skin losses (sweating, burns)
2. HYPOvolaemic hypernatraemia + HIGH urinary Na+: loop diuretics, osmotic diuresis (e.g. uncontrolled DM, glucose, mannitol following initial hyponatraemia), DI
3. EUVOlaemic hypernatraemia: tachypnoea, skin (sweating, fever), DI
4. HYPERvolaemic hypernatraemia: Conn’s syndrome, inappropriate hypertonic saline

Question 23

SUMMARY CARD:

• What are the TWO types of DI (+ Sx)?
• Ix?
• Mx?

Answer 23

Nephrogenic vs Cranial diabetes insipidus

Sx = lethargy, thirst, irritability, confusion, coma, fits –> due to ↑Na+
Clinically EUVOLAEMIC, but DILUTE urine

CDI = lack of/ no ADH production

• Causes = surgery, trauma, craniopharyngioma, autoimmune hypophysitis (from CTLA-4 ipilimumab)
• Mx = desmopressin

NDI = receptor defect leads to insensitivity to ADH

• Causes = drugs (e.g. lithium, demecocycline)
• Mx = thiazide diuretics

Ix:

• Check electrolytes to rule out other causes
• Plasma (normal / high) + urine osmolality (LOW)

8-hour water deprivation test:
* If urine to plasma (U:P) osmolality ratio > 2, then it’s normal (normal concentration ability)
* If urine osmolality increases after administration of desmopressin –> CDI
* If urine osmolality does not change after administration of desmopressin –> NDI

Question 24

SUMMARY CARD:

What is the general management of hypernatraemia?

Answer 24

1. Drink more water
2. SLOW IV fluids as usually hypovolaemic cause (can use saline, dextrose or Hartmann’s)
3. Try IV dextrose if no improvement (1L/ 6hrs)

MEASURE urine output + plasma Na+ to guide Mx

Question 25

# DISEASE: 45F - severe **D&V** following BBQ Ix = **Na+ 150** mmol/L, **low** urinary Na+ What is the type of hypernatraemia? BONUS: Mx?

Answer 25

`Hypovolaemic hypernatraemia` due to water>electrolyte losses in D&V Mx = encourage oral fluid intake (if not possible, slow IV fluids)

Question 26

# DISEASE: 60M - irritable + thirsty PMH cirrhosis (on **furosemide**) Ix = **↑Na+**, **↑ urinary Na+** What type of hypernatraemia is this?

Answer 26

`Hypovolaemic hypernatraemia` due to loop diuretic use

Question 27

# DISEASE: 40F - polyuria + polydipsia **no** signs of dehydration or fluid overload Ix = **↑Na+**, **low** urinary Na+ water deprivation test shows **U:P < 2** What to administer next + what the different results mean (+Mx)?

Answer 27

`Administer desmopressin` **CDI** = responsive, concentrates urine --> Mx = `desmopressin` **NDI** = unresponsive, urine conc remains the same --> Mx = `thiazide diuretic` e.g. indapamide, bendroflumethiazide

Question 28

# DISEASE: 56M - confusion, irritability PMH - **poorly controlled hypertension** despite trialing several different Tx U&Es: **↑Na+, ↓ K+** Urinalysis: **↑K+** * What is the diagnosis? * Ix? * Mx?

Answer 28

* `Conn's syndrome` = primary **hyperaldosteronism** (most commonly caused by adrenal hyperplasia) * Ix = `aldosterone:renin ratio` (**HIGH**) * Mx = `spironolactone` (potassium-sparing diuretic - aldosterone antagonist) * Long-term Mx = laparoscopic adrenalectomy (if malignant or unresponsive to medical therapy)

Question 29

# SUMMARY CARD: * What is the normal range for [K+]? * Where is K+ normally found?

Answer 29

3.5-5.0 mmol/L It is mostly only an intracellular cation (only 2% found extracellularly)

Question 30

# SUMMARY CARD: * What is mild vs severe hypokalaemia and their `Mx`? * Sx of hypokalaemia (+ findings on ECG)?

Answer 30

Hypokalaemia, **< 3.5**mmol/L, is caused by either a `depletion of K+` or due to a `shift of K+ into cells` **Moderate** hypokalaemia = **3.0-3.5** mmol/L --> **Mx** is `oral KCl` (2 SandoK tablets TDS for 48hrs) then `recheck` serum K+ **Severe** hypokalaemia = **< 3.0**mmol/L (↑ risk of cardiac arrest) --> **Mx** = `IV KCl` (max rate of 10 mmol/hr or else ↑ risk of arrhythmia) **Clinical features** (everything is SLOW): `hypo`tonia, `hypo`reflexia, paralytic ileus, muscle weakness, cardiac arrhythmias On **ECG**: `flat/inverted t-waves`, prominent u-waves, prolonged PR interval + ST depression

Question 31

# SUMMARY CARD What are some causes for hypokalaemia?

Answer 31

Hypokalaemia causes that result in **ALKALOSIS**: * `GI` loss: **D&V** * `Renal` loss: **hyperaldosteronism** (suspect if ↑BP, ↑Na+, ↓K+), loop & thiazide **diuretics** NOTE: loop diuretics block Na+/K+/Cl- transporter = reduced reabsorption of all 3 NOTE: Normally, in the CD, Na+ reabsorption is exchanges for K+ excretion --> thiazide diuretics block Na+ reabsorption earlier in the nephron so more Na+ reaches the CD, so more Na+ is reabsorbed as more K+ is excreted out * `Redistribution` into cells e.g. insulin, salbubtamol, refeeding syndrome * `Mg2+ deficiency` (because Mg2+ deficiency can cause ↑K+ wasting) --> Mx = Mg2+ replacement alongside KCl Hypokalaemia causes that result in **ACIDOSIS**: * `Renal tubular acidosis` types 1 & 2 * Type `1` = most **severe**; distal failure of H+ excretion and subsequent acidosis + ↓K+ (failed H+/K+ pump) * Type `2` = **milder**, proximal failure to reabsorb bicarbonate --> leads to acidosis + ↓K+

Question 32

# SUMMARY CARD: * What is hyperkalaemia? * What are some Sx of hyperkalaemia (+ ECG changes)? * Mx?

Answer 32

* [K+] **> 5.0** mmol/L, either caused by `reduced excretion` or `release of intracellular K+` * Sx = **weakness, paralysis, paraesthesia** * ECG changes: small / loss of p waves, `tall tented T waves`, widened QRS complex `Initiate Mx if`: K+ >5.5 w/ ECG changes **OR** K+ > 6.5 regardless of ECG changes * **10mls 10% calcium gluconate over 10 minutes** – cardioprotective (it doesn't do anything to the K+) * IV **insulin** w/ dextrose * Nebulised **salbutamol** as an adjunct * Consider **calcium resonium** (K+ binders - binds to K+ in the gut) 15g PO or 30g PR * NOTE: cardiac monitoring for those on Digoxin as IV calcium can precipitate arrhythmias NOTE: if K+ sample > 7 mmol/L and asymptomatic --> `redo sample` (may be raised due to haemolysis in the sample)

Question 33

# SUMMARY CARD: What are some causes of hyperkalaemia?

Answer 33

Hyperkalaemia can be caused by excessive intake, release of intracellular K+, OR decreased excretion **Excessive intake:** * Oral / parenteral * Blood transfusion **Transcellular movement ICF>ECF:** * Acidosis (due to H+/K+ cotransporter) * Insulin shortage (i.e. `DKA`) * Tissue damage e.g. `rhabdomyolysis` **Decreased excretion:** * Acute `renal failure` * Drugs e.g. `spironolactone` (K+ sparing diuretic, NSAIDs, ACEi, ARBs * `Addison's` disease (↓Na+, ↑K+) * Type `4` renal tubular acidosis (aldosterone deficiency or resistance leads to ↓Na+, ↑K+) OR may be due to artefact e.g. `haemolysis` of the sample

Question 34

# DISEASE: 60M - muscle **weakness**, `hypo`tonia, `hypo`reflexia ECG: `flat t-waves` + **u-waves, PR prolongation** U&Es: **K+ 3.2 mmol/L** PMH: recently started `indapimide` * Cause of this electrolyte abnormality? * Mx?

Answer 34

hypokalaemia due to thiazide diuretic (i.e. indapimide) If K+ **3.0-3.5** mmol/L, **Mx** = `oral KCl` (2 SandoK tablets TDS for 48hrs) then `recheck` serum K+

Question 35

# DISEASE: 70F - muscle weakness PMH: HF currently on furosemide, dose recently increased * What is the most likely electrolyte abnormality? * Assuming it caused a severe electrolyte abnormality, what is the Mx?

Answer 35

Hypokalaemia due to loop diuretic If **severe** hypokalaemia (**< 3.0**mmol/L) --> ↑ risk of cardiac arrest, therefore **Mx** = `IV KCl` (max rate of 10 mmol/hr or else ↑ risk of arrhythmia)

Question 36

# DISEASE: 55M - muscle **weakness + tingling** PMH: **alcohol** misuse and **poor diet** presents K+ **3.2 mmol/L** What other electrolyte abnormality should be screened for?

Answer 36

Check for Mg2+ deficiency

Question 37

# DISEASE: What is the difference in [K+] between type 1+2 RTA and Type 4 RTA?

Answer 37

Type `1` (failure of H+ excretion) + `2` (failure of bicarb reabsorption) = **acidosis & hypokalaemia** Type `4` = **hyperkalaemia** (due to aldosterone deficiency / resistance)

Question 38

# DISEASE: 72M - found after a **fall** complaints of severe **muscle pain + dark urine** Ix = **K+ 6.6** mmol/L, elevated **Cr** * Cause of hyperkalaemia? * Mx?

Answer 38

Rhabdomyolysis --> long lie = breakdown of muscle tissue = release of intracellular K+ Mx for [K+] >6.5 mmol/L: * **10mls 10% calcium gluconate over 10 minutes** – cardioprotective (it doesn't do anything to the K+) * IV **insulin** w/ dextrose * Nebulised **salbutamol** as an adjunct * Consider **calcium resonium** (K+ binders - binds to K+ in the gut) 15g PO or 30g PR

Question 39

# DISEASE: 65F - muscle weakness + tingling, nausea PMH: HF --> treated with spironolactone Ix = 5.7 mmol/L * Reason for hyperkalaemia? * Important Ix?

Answer 39

**Spironolactone** (`K+ sparing diuretic`) can cause hyperkalaemia Important to do `ECG` --> may show tall t waves + absent p-waves (warrants immediate Mx)

Question 40

# SUMMARY CARD: What are the steps to interpreting acid-base balance on a blood gas?

Answer 40

**1. pH** * Low = acidosis * High = alkalosis **2. CO2** * acidosis + ↑CO2 = respiratory acidosis * acidosis + ↓CO2 = partially compensated metabolic acidosis * alkalosis + ↑CO2 = partially compensated metabolic alkalosis **3. HCO3-** * alkalosis + ↑ HCO3- = metabolic alkalosis * alkalosis + ↓HCO3- = partially compensated respiratory alkalosis * acidosis + ↓HCO3- = partially compensated respiratory acidosis **4. Consider compensation:** * normal pH = fully compensated * abnormal pH = partial compensation

Question 41

# SUMMARY CARD: * What is an anion gap? * What is the equation to calculate anion gap? * What does a raised anion gap mean?

Answer 41

The anion gap helps **determine the concentration of unmeasured ions** in the plasma as it is the difference between the [principal cations] and [principal anions] As the anion gap is largely controlled by albumin, beware of `hypoalbuminaemia` `(Na + K) - (Cl + HCO3)` = anion gap Normal range = **14-18** mmol/L It is also useful to determine gas results that are 50/50 e.g. pH 7.5 (high), pCO2 2.0 (low), pO2 11 (normal), HCO3 12 (low) - is this resp alk w/ met comp or met alk w/ resp comp? Mneumonic for **RAISED anion gap** (i.e. due to unmeasured ions) - `KULT`: * `K`etoacidosis (**DKA**, alcoholic, starvation) * `U`raemia (**renal** failure) * `L`**actic acidosis** (RARE SE of **metformin**) * `T`oxins (**ethylene glycol** AKA antifreeze, methanol, **salicylate**, paraldehyde) NOTE: `salicylate` (aspirin) poisoning can cause **respiratory alkalosis FIRST, followed by metabolic acidosis**

Question 42

# SUMMARY CARD: What are some causes of metabolic acidosis? How is metabolic acidosis compensated?

Answer 42

Causes of metabolic acidosis can be split into `normal` **VS** `raised` anion gap `NORMAL` **anion gap (14-18 mmol/L):** * **Diarrhoea** (loss of HCO3- in small bowel) * Acetazolamide (CA inhibitor) * Pancreatic stoma (loss of HCO3-) * **Addison's** disease (↓Na+, ↑K+ --> K+/H+ cotransporter) * **Renal tubular acidosis** (due to decreased H+ excretion) * Ammonium chloride ingestion (found in batteries) `RAISED` **anion gap (>18 mmol/L):** * **Ketones** (alcohol, DKA, starvation) * **Lactic acid** (sepsis, shock, ischaemia, rare SE of metformin) * Ethanol * **Aspirin** (starts w/ resp alk, before met acidosis) * **Biguanides** (metformin --> causes lactic acidosis) * Ethylene glucol * Uraemia `Compensation = hyperventilation`

Question 43

# SUMMARY CARD: What is renal tubular acidosis and the 4 different types? BONUS: what is Fanconi syndrome? | hint: RTA = met acidosis; fanconi = failure of PCT resorption

Answer 43

NOTE: majority of HCO3- is absorbed in PCT * **Type** `1` (`Distal` RTA) = **SEVERE**, due to alpha intercalated `failure to secrete H+` and resorb K+ leads to profound **metabolic acidosis + hypokalaemia + renal stones** * **Type** `2` (`Proximal` RTA) = moderate, failure of proximal tubular cells to reabsorb HCO3- leads to metabolic acidosis + hypokalaemia * **Type** `3`: mixture of types 1 + 2 * **Type** `4`: adrenal failure (aldosterone deficiency or resistance) leads to ↓Na+, ↑K+, mild reduction in serum pH `Fanconi syndrome` = `complete failure` of **PCT kidney reabsorption** **Sx** of Fanconi = **glycosuria**, failure to thrive, **Type 2** renal tubular acidosis, **hypokalaemia**, proteinuria + hyperuricosuria `Causes` of Fanconi: * Wilson’s (also associated with T1 RTA) * Tetracyclines * MM * Lead poisoning

Question 44

# SUMMARY CARD: What are some causes of metabolic alkalosis? How is it compensated?

Answer 44

* **Vomiting** e.g. pyloric stenosis, bulimia (H+ loss) * **Loop diuretics** (K+ depletion --> H+/K+ pump) * ↓K+ * **Conn's** (hyperaldosteronism = ↓K+) * Antacid use * Burns Compensation = hypoventilation

Question 45

# SUMMARY CARD: What are some causes of respiratory acidosis? How is it compensated?

Answer 45

* `Hypoventilation` (Type 2 resp failure) * **Acute / chronic lung disease** (e.g. acute asthma attack, COPD) NOTE: COPD causes chronic respiratory acidosis; pink puffers (AKA breathlessness) + blue bloaters (AKA no longer breathless) --> maintain pO2 88-92% as CO2 is a driver for ventilation * `Opioids` * Sedatives * **Neuromuscular weakness** NOTE: normal / high pCO2 is worrying as it may signal exhaustion --> v. important to ventilate! `Compensation: renal retention of HCO3-`

Question 46

# SUMMARY CARD: What is the difference between Type 1 and Type 2 respiratory failure?

Answer 46

`Type 1: normal pCO2 but low pO2` **Causes of Type 1:** * Reduced ventilation and normal perfusion (e.g. **pneumonia**, pulmonary oedema, bronchoconstriction) * Reduced perfusion with normal ventilation (e.g. **pulmonary embolism**) `Type 2: low pO2 AND high pCO2` --> occurs due to `HYPO`**ventilation** * **COPD** (acute exacerbation) * Reduced compliance of the lung tissue/chest wall e.g. **pneumonia**, rib fractures, obesity * Reduced strength of the respiratory muscles e.g. **GBS, NMD** * Reduced respiratory drive e.g. **opioids**, sedatives

Question 47

# SUMMARY CARD: What are some causes of respiratory alkalosis? How is it compensated?

Answer 47

* **Hyperventilation** e.g. anxiety * High altitude (hypoxaemia) * **Salicylate** poisoning (first resp alk, followed by met acidosis) `Compensation = reduced renal HCO3- reabsorption`

Question 48

# DISEASE: 28F - found to be persistently `acidotic` and `hypokalaemic` 2 months ago had **right loin pain**, was treated for sepsis (not gynae related) Currently, no FLAWS but acidotic + low K+ * Diagnosis?

Answer 48

Renal tubular acidosis Type 1 - due to triad of renal stones + metabolic acidosis + ↓K+ NOTE: type 2 does not present with renal stones as it is milder

Question 49

# DISEASE: 15F - panic attack What acid-base imbalance is expected?

Answer 49

Resp alkalosis

Question 50

# DISEASE: In general, what pH imbalance is associated with: * hypokalaemia * hyperkalaemia

Answer 50

1. `↓K+ = alkalosis` due to H+/K+ pump (H+ exchanged to pump out K+) 2. `↑K+ = acidosis` due to H+/K+ pump (H+ pumped out to drive K+ into cells)

Question 51

# DISEASE 24F - appears unwell + dehydrated PMH: **T1DM** pH 7.20 BE -12 Na 155mmol/L K 5mmol/L Cl 115mmol/L HCO3 20mmol/L Glucose 27mmol/L Lactate 2mmol/L Urea (15mmol/L) Serum osmolarity which is 365mmol/L * What is the anion responsible for the patient's metabolic acidosis?

Answer 51

always calculate anion gap in metabolic acidosis to differentiate between different causes Anion gap = (Na + K) - (Cl + HCO3) = **25** (`RAISED`) Therefore, due to PMH of T1DM, most likely unmeasured ion is `ketones`

Question 52

# DISEASE: 30F - BP 84/36, 3/7 hx of productive cough and fevers PMH: **coeliac disease** **pH 7.21** BE -12 `Na 131mmol/L` `K 6mmol/L` Cl 109mmol/L HCO3 12mmol/L Glucose 3mmol/L Lactate 2mmol/L Urea (6mmol/L) and serum osmolarity which is 290mmol/L. Inflammatory markers are normal. * What is the serum osmolarity? * And anion gap? * What condition is responsible for of her metabolic acidosis?

Answer 52

Osmolarity = `2(Na + K) + urea + glucose` So, the pt's serum osmolarity = **289** mmol/L Anion gap = (Na + K) - (Cl + HCO3) = **16** (normal) Diagnosis: `Addison's disease` --> due to normal anion gap +↓Na+ and ↑K+ (causes acidosis due to H+/K+ cotransporter)

Question 53

# DISEASE: `Inadequate function` of the `proximal` renal tubules TRIAD of **glucosuria** + **hypophosphatemia** + **hyperuricosuria** * Diagnosis?

Answer 53

Fanconi syndrome = `complete failure` of **PCT kidney reabsorption**

Question 54

# DISEASE: 21F - **overdose** of medication, N&V and **ringing** in ears PMH: **EUPD** pH `7.5` pCO2 `low` HCO3- `low` * What has she most likely overdosed on?

Answer 54

Aspirin (salicylate) Causes resp alk followed by met acidosis

Question 55

# DISEASE: 76M - `acute COPD exacerbation` Arterial blood gas shows: pH **7.30** (7.35-7.45) PaCO2 **9** kPa (4.7-6.0 kPa) PaO2 **10** kPa (11-13 kPa on 21% FiO2) HCO3- **38** mmol/L (22-26 mEq/L) * What type of respiratory failure does he have? * How would you describe this patient’s acid base disturbance?

Answer 55

* Type 2 respiratory failure (low pO2 AND high pCO2) * Partially compensated respiratory acidosis / chronic respiratory acidosis

Question 56

# DISEASE: 1 week old male infant w/ projectile vomiting after feeds Vomit is milky + nonbilious Still hungry after feeds O/E: small mass in epigastrium * What is the diagnosis? * What acid base disturbance would you expect?

Answer 56

pyloric stenosis metabolic alkalosis (due to loss of H+)

Question 57

# DISEASE: 3M - concerns about failure to thrive PMH: rickets and is on appropriate calcium and vitamin D replacement Blood tests show him to be hypokalaemic. Urine dip shows the presence of protein and glucose. The pH of the urine is 8.6 (alkaline). There are no ketones in his blood. * Diagnosis?

Answer 57

`Fanconi syndrome` - complete failure of PCT **Sx** of Fanconi = **glycosuria**, failure to thrive, **Type 2** renal tubular acidosis, **hypokalaemia**, proteinuria + hyperuricosuria

Question 58

# DISEASE: 53F - sudden sharp chest pain Recently returned from Australia ABG: pH **7.49** (NR 7.35-7.45) PaO2 **8.7** kPa (NR: 11-13 kPa on 21% FiO2) PaCO2 **3.1** kPa (NR: 4.7-6.0 kPa) HCO3- **23** mmol/L (NR 22-26 mEq/L) How would you describe this patient’s acid base disturbance?

Answer 58

pulmonary embolism respiratory alkalosis with partial compensation

Question 59

# SUMMARY CARD: Which hormones from the hypothalamus stimulate hormone release from the pituitary? | GnRH, TRH, dopamine, CRH

Answer 59

**Hypothalamus** and `ANTERIOR PITUITARY` (AP) hormones: * **GnRH** and **somatostatin** from hypothalamus stimulates somatotrophs in AP = `somatotrophin` (AKA growth hormone) release * **GnRH** from hypothalamus stimulates gonadotrophs in AP = `gonadotrophin` (AKA LH + FSH) release * **CRH** from hypothalamus stimulates corticotrophs = `ACTH` release * **TRH** from hypothalamus stimulates thyrotrophs = `TSH` release AND `prolactin release` * **Dopamine** from hypothalamus **INHIBITS** lactotrophs = `inhibits prolactin` NOTE: GnRH = Gonadotropin hormone-releasing hormone; CRH = Corticotropin-releasing hormone; TRH = Thyrotropin-releasing hormone; ACTH = adrenocorticotropic hormone **POSTERIOR pituitary hormones:** * Oxytocin * Vasopressin

Question 60

# SUMMARY CARD: What is hypopituitarism? What is the mainstay investigation for hypopituitarism? | Combined pituitary function test

Answer 60

`Hypopituitarism` = **deficiency** in 1 or more **hormones** by the **pituitary gland** due to e.g. pituitary `tumours`, traumatic brain injury (`TBI`), or `autoimmune` conditions **Combined pituitary function test:** used to assess hypopituitarism **Procedure:** 1. Patient **fasts** overnight, IV access established, and weight recorded 2. Mix `insulin` dose (0.15 units/kg; to stimulate GH and ACTH), `TRH` 200mcg (to stimulate TSH and prolactin), `LHRH` 100mcg (AKA GnRH, to stimulate LH/FSH) in a 5ml syringe and administer IV 3. Bloods taken for basal thyroxine, glucose, cortisol, GH, LH, FSH, TSH, and prolactin **every 30 minutes for 1 hour** 4. Replace hydrocortisone, T4, estrogen, and GH if needed urgently **Interpretation of results:** **1. Insulin Tolerance Test**: Hypoglycemia (< 2.2mmol/L) triggers `↑ACTH` and `↑GH`. Adequate cortisol response is >170 nmol/l. Adequate GH response is >6mcg/L **2. Thyrotrophin Releasing Hormone Test**: Triggers `↑TSH` and `↑Prolactin`. Normal result is TSH rise to >5 mU/l. Hyperthyroidism shows suppressed TSH, while hypothyroidism shows an exaggerated response. **3. Gonadotrophin Releasing Hormone Test**: Triggers `↑LH/FSH`. Normal peaks can occur at 30 or 60 minutes. Inadequate response may indicate hypopituitarism. Diagnosis of gonadotrophin deficiency is based on basal levels. NOTE: contraindications to CPF test = ischaemic heart disease, epilepsy, untreated hypothyroidism (as it impairs GH + cortisol response)

Question 61

# SUMMARY CARD: What are some causes (+ Sx + Mx) of hypopituitarism?

Answer 61

**Causes:** * **Malignancy** e.g. pituitary adenoma, craniopharyngioma * **Infection** e.g. TB (Mx = RIPE), syphilis (Mx = abx) * **Infiltration** e.g. sarcoidosis, lymphoma * **Iatrogenic** e.g. surgical / trauma / radiation * **Infarct** e.g. Sheehan's or apoplexy **S&S:** * `Generic Sx` = `lethargy`, **weight gain**, ↓ BP, hair loss, myalgia * `↓ sex hormones` = **impotence**, ↓ libido, amenorrhoea * `↓ ACTH` = **Addisonian** crisis * `↓ TSH` = **myxoedema coma** **Ix:** * 9AM cortisol, TFTs, testosterone/oestrogen * CPFT * Imaging **Mx = replacement of hormones:** * ↓ ACTH = Addison's --> `hydrocortisone +/- fludrocortisone` * ↓ TSH = secondary hypothyroidism --> `thyroxine` replacement * ↓ LH/FSH = replace `sex hormones` (testosterone/oestrogen)

Question 62

# SUMMARY CARD: What are the features of these pituitary tumours: 1. Microadenoma 2. Macroadenoma 3. Prolactinoma 4. Non-functioning pituitary adenoma 5. Acromegaly

Answer 62

Pituitary tumours can produce any combination of the pituitary hormones or be non-secreting **1. Microadenoma**: * `< 10mm`, usually benign * MORE likely to be functional e.g.: * `GH secreting` presents w/ Sx of **acromegaly, diabetes, HF, HTN**; leading cause of death is HF * `Prolactin secreting` presents with Sx of **galactorrhoea, gynaecomastia, amenorrhoea, impotence** **2. Macroadenoma:** * `> 10mm` * Can be non-functional or prolactinoma * Compression of optic chiasm = bitemporal hemianopia **3. Prolactinoma:** * Macroprolactinoma >5000 miu/L * Moderate elevation (1000-5000) = microprolactinoma * Mx = `dopamine agonists` e.g. **cabergoline, bromocriptine** **4. Nonfunctioning pituitary adenoma**: * Prolactin up to 5000 * Mx = watch and wait if no Sx **5. Acromegaly:** * `↑GH`, ↑prolactin * Initial Ix = **IGF-1** (↑ in acromegaly) * `OGTT w/ GH (75mg glucose)` = GOLD STANDARD → **>2 mU/L = acromegaly**; < 2 = normal * Mx = **trans-sphenoidal surgery**, 2nd line = octreotide (somatostatin analogue – inhibits GH release), pegvisomant – GH receptor antagonist, cabergoline (DA agonist)

Question 63

# DISEASE: Which of the following results from a Combined Pituitary Function Test (CPFT) would be consistent with a diagnosis of **hypopituitarism**? a) Elevated cortisol and GH levels after insulin administration b) Elevated TSH and prolactin levels after TRH administration c) Low cortisol and GH levels after insulin administration d) Elevated LH and FSH levels after GnRH administration e) Elevated TSH levels after TRH administration

Answer 63

c) Low cortisol and GH levels after insulin administration (`hypoglycaemia SHOULD trigger ACTH and GH release!`)

Question 64

# DISEASE: A patient with hypopituitarism shows low levels of LH, FSH, and testosterone. Which biochemical test would you perform next to confirm the diagnosis?

Answer 64

GnRH stimulation test (that should trigger a ↑LH/FSH)

Question 65

# DISEASE: 28F - `amenorrhea, galactorrhea + visual disturbances` Prolactin >6000 MRI reveals a `12 mm` pituitary mass * What is the most likely diagnosis? * BONUS: what is the Mx?

Answer 65

Prolactinoma Mx = cabergoline, definitive = transphenoidal surgery

Question 66

# DISEASE: Which **initial test** is most appropriate for a patient with **suspected acromegaly** due to a pituitary tumour?

Answer 66

IGF-1 (raised)

Question 67

# DISEASE: 55F - **pituitary** tumour presents with high `blood pressure, diabetes, and weight gain` * What hormone is being secreted?

Answer 67

Cushing's disease - ACTH secretion causing hypercortisolism

Question 68

# SUMMARY CARD: What is the hypothalamo-pituitary-thyroid axis? How is thyroxine synthesised?

Answer 68

**HPT axis:** * **Hypothalamus** detects low plasma thyroxine → releases thyrotropin releasing hormone (`TRH`) → stimulates **anterior pituitary** to release thyroid-stimulating hormone / thyrotropin (`TSH`) → stimulates **thyroid** gland to release `T3/T4` * **T3/T4** has a `negative feedback` mechanism on the hypothalamus and pituitary (**suppresses TRH and TSH** production respectively) * NOTE: T3 is the active form, T4 is converted to T3 in the liver and muscle cells **Thyroxine synthesis:** * Iodide --`thyroid peroxidase`--> **Iodine** * Iodine enters the colloid and iodinates tyrosine residues on thyroglobulin forming monoiodotyrosine (MIT) + diiodotyrosine (DIT) * These go on to form T3 (triiodothyronine) and T4 (thyroxine) * Then T4 converted to T3 in the periphery * NOTE: perchlorate controls whole process

Question 69

# SUMMARY CARD: Features of the following `hypothyroid` conditions (RFs, Sx, Ix, + Mx): **Primary hypothyroidism:** 1. Iodine deficiency 2. Hashimoto's thyroiditis 3. Primary atrophic hypothyroidism 4. Subacute thyroiditis (AKA De Quervains) 5. Riedel’s thyroiditis 6. Drug-induced **Secondary hypothyroidism:** 1. Post-partum (Sheehan's) 2. Pituitary apoplexy / adenoma / surgery **Other:** 1. Subclinical hypothyroidism 2. Sick euthyroid 3. Treated hypothyroidism

Answer 69

**S&S of hypothyroidism** = weight gain, cold intolerance, depression, dry skin, hair loss, fatigue, constipation, bradycardia Ix = `TSH + T3/T4` (2 sets of bloods 3 months apart) Mx = **levothyroxine replacement** (6 weekly checks until stable TSH) If `myxoedema coma` (e.g. hypothermia < 35.5°C, bradycardia) → MEDICAL emergency = **IV T3+T4** AND glucocorticoids e.g. **IV hydrocortisone** until adrenal insufficiency is excluded **Primary hypothyroidism - generally `↓T4 ↑TSH`:** * `Severe iodine deficiency` = most **COMMON** CAUSE of hypothyroidism worldwide * `Autoimmune thyroiditis` = most **common** cause in the developed world / UK * `Primary strophic hypothyroidism` = diffuse lymphocytic infiltration causes atropy → **SMALL goitre**; associated w/ other AI conditions e.g. pernicious anaemia, vitiligo * `Hashimoto's thyroiditis` = **anti-thyroid peroxidase** Abs or anti-thyroglobulin Abs, **diffuse goitre**, ↑risk of developing NHL * `Subacute` = post-viral infection → damaged thyroid follicles initially spill thyroxine into the blood (hyperthyroid) then become hypothyroid as follicles heal (self-limiting, 6-8 weeks) * `Riedel's thyroiditis` = dense fibrosis replaces normal thyroid parenchyma → **painless, woody** thyroid * `Drug-induced` = antithyroid drugs, lithium, amiodarone * NOTE: amiodarone can cause hyper or hypothyroidism as it damaged thyroid cells (hypo) but also contains iodine (hyper) **Primary hypothyroidism - generally `↓TSH ↓T4`:** * Causes include: pituitary apoplexy, pituitary tumour, transphenoidal surgery, post-partum (Sheehan's) **Other:** * **Subclinical hypothyroidism** = `NORMAL T3/T4 but ↑ TSH` * **Sick euthyroid** = occurs w/ any severe illness as body shuts down metabolism to conserve energy so `↓ T3/T4 , normal TSH` * **Treated hypothyroidism** can present similarly to subclinical hypothyroidism = NORMAL T3/T4 but ↑TSH

Question 70

# SUMMARY CARD: How is thyroid function affected in pregnancy? What is neonatal hypothyroidism?

Answer 70

* `hCG` has an analogous `structure to TSH`, rise in hCG in first trimester → free T4 slight increase * TBG levels increase in pregnancy and later in pregnancy, hCG levels drop → T4 levels drop and TSH rises slightly **Neonatal hypothyroidism:** * Diagnosed as part of `Guthrie test` (48-72hrs in) * NOTE: do not want to diagnose too early because if you measure too early the TSH might be erroneously high due to maternal TSH in the blood * If `not` diagnosed and treated w/ levothyroxine within the first four weeks, it causes **irreversible cognitive impairment**

Question 71

# SUMMARY CARD: Features of the following `hyperthyroid` conditions (RFs, Ix, Mx): **Primary hyperthyroidism:** 1. Graves' disease 2. Solitary toxic nodule 3. Plummer's (toxic multinodular) 4. Subacute thyroiditis (AKA De Quervains) 5. Drug-induced 6. Ectopic 7. Post-partum **Secondary hyperthyroidism:** 1. TSH secreting tumour 2. Thyroid hormone resistance **Other:** 1. Subclinical hyperthyroidism

Answer 71

**S&S of hyperthyroidism** = weight loss, heat intolerance, irritability, difficulty sleeping Ix = `TSH + T3/T4` Mx = **Carbimazole** (either titrate, or block and replace w/ levothyroxine); radio-iodine therapy (CI: pregnancy / breastfeeding); thyroidectomy If `thyroid storm` (e.g. hyperthermia > 41°C, tachycardia) → MEDICAL emergency = **IV propylthiouracil** + IV hydrocortisone (+ Lugol solution) **Primary hyperthyroidism - generally `↑T4 ↓TSH`:** * `Graves' disease` = **anti-TSH-R** antibodies; Sx triad of **thyroid acropachy, pretibial myxoedema + exophthalmos**; **diffuse** goitre w/ high uptake on technetium scan * Single or multi- `toxic nodules` = patchy technetium scan uptake; Mx = radioiodine * `Subacute` = post-viral infection → damaged thyroid follicles initially spill thyroxine into the blood * `Drug-induced` e.g. thyroxine, amiodarone * `Ectopic` e.g.trophoblastic tumour, struma ovarii * `Post-partum` (damaged thyroid follicles spill T3/T4 into the blood) **Secondary hyperthyroidism - generally `↑TSH ↑T3/T4`:** * TSH secreting tumour or thyroid hormone reisstance **Other:** * **Subclinical hyperthyroidism** = `NORMAL T3/T4 but ↓ TSH`

Question 72

# SUMMARY CARD: What are some features of the following types of thyroid cancer: 1. Papillary 2. Follicular 3. Medullary 4. Anaplastic 5. MALT lymphoma (due to Hashimoto's)

Answer 72

* May present as solitary painless nodule (hard + immovable) * Usually non-functioning **1. Papillary** * `Most common` (70%) + best prognosis * RF = exposure to ionising radiation during childhood * `Psammoma bodies + Orphan Annie nuclei` * Mx = total thyroidectomy (TT) +/- radioiodine (to wipe out last survivors) + levothyroxine * Monitor **thyroglobulin** for recurrence **2. Follicular adenocarcinoma** * `2nd` most common (20%) * RF = low dietary iodine * **Vascular invasion** (can spread easily) * Mx = total thyroidectomy + radioiodine * NOTE: Hurthle cell = rare variant of follicular thyroid cancer **3. Medullary** * Arise from `c-cells` found in the thyroid medulla * C-cells that produce `calcitonin` (tumour marker), linked to MEN2 * Causes diarrhoea + flushing of the skin **4. Anaplastic** * Most **undifferentiated** + `poor prognosis` * Elderly * Rapid growth * Giant and spindle shaped cells + `pleomorphic giant cells` **5. MALT lymphoma** (due to Hashimoto's) * Chronic Hashimoto's = lymphocytic proliferation = MALT lymphoma

Question 73

# SUMMARY CARD: What are the Multiple Endocrine Neoplasia (MEN) syndromes?

Answer 73

**MEN1 (3Ps)**: `P`ituitary adenoma, `P`ancreatic (e.g. insulinoma) + `P`arathyroid hyperplasia **MEN2A (2Ps, 1M)**: `P`arathyroid hyperplasia, `P`haeochromocytoma, `M`edullary thyroid cancer **MEN2B (1P, 3Ms)**: `P`haeochromocytoma, `M`edullary thyroid cancer, `M`ucocutaneous neuromas (& `M`arfanoid)

Question 74

# DISEASE: What is the most common cause of hypothyroidism worldwide vs UK?

Answer 74

Iodine deficiency vs autoimmune (e.g. Hashimoto's)

Question 75

# DISEASE: 45F - diffuse goiter and anti-thyroid peroxidase antibodies Bloods: ↓T4, ↑TSH Diagnosis?

Answer 75

Hashimoto's thyroiditis

Question 76

# DISEASE: Which laboratory finding is indicative of **subclinical hypothyroidism**? If subclinical hypothyroidism is found on a blood test - what is the next step in management? | T4 and TSH

Answer 76

Normal T4 and T3 with elevated TSH Repeat TSH + T3/T4 levels in 6 weeks (only treat if symptomatic)

Question 77

# DISEASE: 23M - bradycardia, hypothermia, and altered mental status Bloods = low T3, T4, and elevated TSH * What is the diagnosis? * Mx?

Answer 77

Myxoedema coma Mx = `IV T3+T4` **AND** glucocorticoids e.g `IV hydrocortisone` until adrenal insufficiency is excluded

Question 78

# DISEASE: What is the initial management for a patient presenting with a thyroid storm?

Answer 78

IV hydrocortisone and IV propylthiouracil

Question 79

# DISEASE: 60M - solitary, painless thyroid nodule USS = solid, hypoechoic mass with microcalcifications Fine-needle aspiration biopsy = psammoma bodies * Diagnosis?

Answer 79

Papillary thyroid carcinoma

Question 80

# DISEASE: Which type of thyroid cancer is associated with MEN2 syndrome and elevated calcitonin levels?

Answer 80

Medullary thyroid cancer

Question 81

# SUMMARY CARD: What hormones are produced by the adrenals and what are their roles?

Answer 81

**Mnemonic: GFR + sweeter as you go down** **Cortex:** Zona `g`lomerulosa = `aldosterone` (mineralocorticoid; retains Na+, excretes K+) Zona `f`asciculata = `cortisol` (glucocorticoid; diurnal, sleep wake cycle) Zona `r`eticularis = `DHEA` (precursor to sex steroids = androgens + oestrogen) **Medulla:** (nor)adrenaline (AKA catecholamines)

Question 82

# SUMMARY CARD: What are features of the following adrenal conditions: Zona glomerulosa (aldosterone): 1. Addison's disease (adrenal insufficiency) 2. Conn's syndrome (hyperaldosteronism)

Answer 82

**1. Addison's disease (adrenal insufficiency)** * Causes: **autoimmune** (primary cause in Europe), **TB** (primary causes worldwide) * Sx = tan skin (POMC → ACTH + MSH), lethargy, depression * Bloods = **↓Na+, ↑K+** * 9AM cortisol >350 excludes Addison's * `Short synACTHen test` → serum **cortisol < double** at 30 mins indicates Addison's * Serum ACTH: ↑ = primary, ↓ = secondary * **Hormone replacement** w/ hydrocortisone (glucocorticoid) +/- fludrocortisone (mineralocorticoid) * NOTE: double steroid dose on sick days * **Addisonian crisis** = hypotensice shock, ↑HR, hypothermic, ↓Na+, ↑K+, ↑urea → **Mx** = `IV fluids` 0.9% NaCl + 50ml dextrose if hypoglycaemic + `IM 200mg hydrocortisone bolus` **2. Conn's syndrome (hyperaldosteronism)**: * **Adrenal hyperplasia** = most common cause * Sx = `treatment resistant HTN` * Bloods: **↑Na+, ↓K+** * ↑ `Aldosterone:renin ratio` (renin suppressed due to high levels of aldosterone) * Aldosterone antagonists & K+ sparing diuretics * If >4cm, consider surgical excision

Question 83

# SUMMARY CARD: What are features of the following adrenal conditions: Zona fasciculata (cortisol): 1. Cushing's syndrome (hypercortisolism) 2. ACTH deficiency

Answer 83

**1. Cushing's syndrome (hypercortisolism)**: * Causes = **ACTH dependent** e.g. Cushing's disease (pituitary tumour, most common) or ectopic (SCLC); OR **ACTH-independent** e.g. adrenal adenoma, adrenal hyperplasia or iatrogenic steroid use * Sx = moon face, central obesity, striae, acne, HTN, diabetes, proximal myopathy, hirsutism, bruising * Bloods: ↑ 9AM cortisol * Low dose dexamethasone test fails to suppress cortisol levels * Inferior pituitary petrosal sinus sampling (IPPSS): ↑ ACTH = Cushing's disease; ↓ = ectopic * MRI /CT of pituitary * Mx = treat underlying disease **2. ACTH deficiency**: * Causes = `pituitary tumours / surgery`, Sheehan's, etc. * NOTE: increases sensitivity to insulin * **Sx** = fatigue, weakness, weight loss, hypotension, hypoglycemia, nausea, vomiting, decreased libido, and amenorrhea in women * Bloods: **↓ ACTH, ↓ cortisol** * Combined pituitary function test to identify hypopituitarism * Mx = `hormone replacement` e.g. hydrocortisone

Question 84

# SUMMARY CARD: What are features of the following adrenal conditions: Zona reticularis (DHEA): 1. CAH

Answer 84

* Most common cause = `21-alpha hydroxylase deficiency` * In neonates = **ambiguous genitalia** in females, **salt-wasting crisis** (vomiting, dehydration, electrolyte imbalances) * In children = precocious puberty, rapid growth, early skeletal maturation * Blood tests = `↑ 17-hydroxyprogesterone, ↓ cortisol levels, ↑ ACTH` * Hormone replacement = **hydrocortisone** (glucocorticoid suppresses ACTH) +/- **fludrocortisone** * Genital recontructive surgery in females

Question 85

# SUMMARY CARD: What are features of the following adrenal conditions: Medulla (adrenaline): 1. Phaeochromocytoma

Answer 85

* Causes = `adrenal medulla tumour`, periperhal neural tumour * Triad of Sx = **headaches + HTN + hyperhidrosis** * Arrhythmias * Plasma metanephrines + 24hr urinary catecholamines / **metanephrines** * Mx = alpha-blockade first (e.g. `phenoxybenzamine` FIRST ~ 2 week; to prevent unopposed vasoconstriction), THEN `beta blockade` (e.g. propranolol) * Surgical Mx when BP well-controlled LONG NOTE: Alpha receptors are found in the blood vessels and when activated cause vasoconstriction, so an alpha blockade stops vasoconstriction. Beta receptors are found in the heart and when activated increases HR, so a beta blockade reduced HR. If a the beta blockade is given FIRST, then the reduction in HR will cause the body to automatically vasoconstrict to preserve the BP, and the alpha blockade then won't work.

Question 86

# DISEASE: 40F - fatigue, depression + tan skin Bloods = decreased sodium and increased potassium levels Diagnosis? Ix to confirm the diagnosis?

Answer 86

Addison's disease Short synACTHen test fails to double cortisol levels

Question 87

# DISEASE: What is the primary cause of Addison’s disease in Europe vs worldwide?

Answer 87

autoimmune vs TB

Question 88

# DISEASE: What is the most common cause of primary hyperaldosteronism?

Answer 88

Adrenal hyperplasia

Question 89

# DISEASE: 30M - paroxysmal episodes of headaches, hypertension + hyperhidrosis Diagnosis? Mx?

Answer 89

Phaeochromocytoma Mx = alpha-blockade first (e.g. phenoxybenzamine FIRST ~ 2 week; to prevent unopposed vasoconstriction), THEN beta blockade (e.g. propranolol) Surgical Mx when BP well-controlled

Question 90

# DISEASE: Which condition is characterised by increased plasma metanephrines and 24-hour urinary catecholamines/metanephrines

Answer 90

Phaeochromocytoma

Question 91

# DISEASE: Which enzyme deficiency is the most common cause of congenital adrenal hyperplasia?

Answer 91

21-alpha hydroxylase

Question 92

# DISEASE: 55F - weight gain, central obesity, striae, + proximal muscle weakness Most likely hormone imbalance?

Answer 92

Cushing's syndrome - high cortisol

Question 93

# DISEASE: What is the primary cause of ACTH deficiency?

Answer 93

pituitary adenoma

Question 94

# DISEASE: What is a potential complication of untreated congenital adrenal hyperplasia (CAH) in neonates?

Answer 94

Adrenal (AKA addisonian) crisis

Question 95

# SUMMARY CARD: What is the renin angiotensin aldosterone system (RAAS)? What conditions affect aldosterone?

Answer 95

**Angiotensinogen** ---`renin`---> **angiotensin 1** ---`ACE`---> **angiotensin 2** Angiotensin 2 acts on receptors in the adrenal glomerulosa to stimulate `aldosterone release` **LOW aldosterone (↑ K+):** * Addison's disease * ACE inhibitors (as angiotensin isn't formed to act on the adrenals) * ARBs (as they block the receptors in the adrenals so angiotensin 2 can't act on them) * RTA type 4 (is like adrenal failure, presents like Addison's) * K+ sparing diuretics e.g. spironolactone * Diabetes insipidus (i.e. vasopressin insufficiency / resistance) **HIGH aldosterone (↓ K+):** * Conn's syndrome * RTA type 1 (affects DCT) * Guitelman's syndrome (Affects DCT) * RTA type 2 (affects PCT) * Fanconi syndrome (RTA type 2 plus syndrome) * Loop diuretics e.g. furosemide * Barter's syndrome (like if you took lots of loop diuretics)

Question 96

# SUMMARY CARD: What is GFR? What markers can be used for eGFR? | glomerular filtration rate

Answer 96

Marker of renal function `Normal = 120ml/min` **3 criteria** to use a marker as an estimate of GFR: * **Freely filtered** * Not bound to plasma proteins + not reabsorbed * `Inulin = GOLD-STANDARD` but needs IV steady state infusion so not used * **Cockcroft-Gault** equation for creatinine and eGFR uses age, sex and **weight** * **MDRD** equation used for creatinine and eGFR uses age, sex and **ethnicity**

Question 97

# SUMMARY CARD: What is AKI? What are the indications for dialysis in AKI?

Answer 97

**AKI:** * **>26** rise in serum Cr within **48hrs** * OR **>50%** rise in serum Cr in past **7 days** * OR **fall** in urine output **< 0.5** mL/kg/hr for >6hrs **Dialysis Indication = AEIOU:** * `A`cidosis * `E`lectrolyte Disturbance * `I`ntoxication i.e. w/ lithium * `O`verload w/ fluids i.e. pulmonary oedema * `U`raemic encephalopathy

Question 98

# SUMMARY CARD: What is CKD (+ its causes)? What are the stages of CKD and how is it managed?

Answer 98

**Causes of CKD** = `diabetes`, atherosclerosis, `HTN`, chronic glomerulonephritis, infection / obstructive uropathy, PCKD **CKD can lead to:** `acidosis + hyperkaelaemia`, `anaemia` due to loss of EPO synthesis + renal bone disease (`secondary hyperparathyroidism`) Use the `eGFR clock` for CKD staging **Renal replacement therapy:** * **Haemodialysis** (Tessio Line or AV fistula) = done 3x a week * OR **peritoneal** dialysis (Tenckoff Catheter, can be done at home) * Renal **transplant** is usually to the `right iliac fossa` and the surgical **scar** is the Rutherford Morrison Scar (Hockey Stick scar in RIF)

Question 99

# SUMMARY CARD: