Chemical Pathology 12 - Meeran's Diabetes CPC (pituitary)

Question 1

What are the 3 biochemical definitions of diabetes?

Answer 1

Fasting PLASMA glucose >7.0mM (nb. this value does not apply to fingerprick whole blood test)

HbA1c > 6.5% (equivalent >48mmol/mol)

2 hour plasma glucose in Glucose Tolerance Test of >11.1mM

Question 2

What HbA1c and OGTT values count as ‘impaired glucose tolerance’?

Answer 2

42-48mmol/mol

7.8-11.1 at 2 hours

Question 3

Recall 3 differentials for metabolic alkalosis

Answer 3

H+ loss via vomiting (see history)
Hypokalaemia
Bicarb ingestion (rennies)

Question 4

recall the causes of acute respiratory acidosis?

Answer 4

pH will rise rapidly and may be because you have stopped breathing entirely

drug induced - opiates, diazepam

Question 5

recall the causes of chronic respiratory acidosis?

Answer 5

e.g. COPD

COPD → lungs slowly fail → pCO2 drifts upwards → become very breathless because CO2 is a potent respiratory stimulus

kidneys will try to compensate by retaining HCO3-

Question 6

Why is CO2 low in ketotic acidosis?

Answer 6

Reduced bicarb due to high ketones (mops up bicarb)

Reduced bicarb = reduced CO2 (Henderson Hasselbach equilibrium)

Also reduced CO2 from hyperventilation

Question 7

What is the calculation for osmolality?

Answer 7

2(Na + K) + Urea + Glucose

Question 8

What is the calculation for anion gap?

Answer 8

Na + K - Cl - HCO3

Question 9

What are some causes of high anion gap?

Answer 9

ketones

ethylene glycol poisoning

lactate (sepsis)

methanol/ethanol

we assume cations (Na/K) = anions (Cl, bicarb, others)

others = anion gap (PO4, SO4 etc)

Question 10

What is a cause for respiratory alkalosis with normal anion gap

Answer 10

anxiety caused by hypoglycaemia (as AG is normal) → primary hyperventilation

↑ pH → plasma proteins start to stick to calcium more than usual → plasma calcium appears normal but less free ionised calcium available → fall in free ionised calcium will result in tetany (which can make patients hyperventilate more)

Question 11

How can hypoglycaemia lead to a respiratory alkalosis?

Answer 11

Can cause significant anxiety –> hyperventilation

Question 12

Why can very high serum omolality cause unconsciousness?

Answer 12

Brain gets VERY dehydrated

Question 13

How will the acid-base disturbance differ between DKA and HHS?

Answer 13

pH is reasonable is HHS

in DKA - met acidosis

Question 14

Recall the treatment for HHS

Answer 14

0.9% saline (500-1,000mL/hour) slowly

Do not give insulin immediately (as insulin will pull glucose into cells and dehydrate them even more)

Question 15

What happens if fluids are given too quickly?

Answer 15

cerebral oedema and death

central pontine myelinolysis

Question 16

What metabolic imbalance is caused by metformin?

Answer 16

Lactic acidosis

Cori cycle: anaerobic glycoysis -> lactate -> liver to be converted to glucose -> returns to muscles and is metabolised to lactate

Metformin can cause lactic acidosis because it inhibits hepatic gluconeogenesis

Normally, excess lactate will be cleared by the kidneys, but in patients with renal failure, the kidneys cannot handle the excess lactic acid

(These are anions so will cause high anion gap, but urine will be negative for ketones)

Question 17

How can acute and chronic renal failure be distinguished?

Answer 17

Renal biopsy

dehydrated tubules

tubules are necrosed but glomeruli intact → ATN

Question 18

How should acute tubular necrosis be managed?

Answer 18

Dialyse for 3 weeks and they willl recover

Question 19

How should diabetic glomerular kidney disease be managed?

Answer 19

This is a lifelong condition that will require lifelong dialysis

Question 20

What is the difference in expected pCO2 in uncompensated metabolic and respiratory acidosis?

Answer 20

Metabolic: low pCO2 (equilibrium pushed right to produce more CO2 but this is breathed off nicely)

Respiratory: high pCO2 (not ventilating properly to get rid of CO2)

Question 21

What is the difference in expected pCO2 in uncompensated metabolic and respiratory alkalosis?

Answer 21

Metabolic: high pCO2 (reduced H+ means resp rate decreases to produce more CO2 to replace H+)

Respiratory: low pCO2 (hyperventilation –> blowing off all CO2)

Question 22

How is respiratory compensation achieved in metabolic alkalosis?

Answer 22

Compensation is making pH better and CO2 worse (done by brain)

N.B. high HCO3- ↑ CO2 due to shift in equilibrium and NOT a form of compensation

However, metabolic alkalosis will inhibit ventilation which will drive the CO2 up further

Extent of compensation limited because ventilation needs to remain sufficient to maintain good oxygen levels → relatively little respiratory compensation for alkalosis

Question 23

How does hypoklaemia affect pH and vice versa?

Answer 23

Hypokalaemia → alkalosis; Alkalosis → hypokalaemia (determine which came first with Hx)

Question 24

How does hypokalaemia cause alkalosis?

Answer 24

Lack of extracellular K for exchange with Na → ↑ H+ enter cells → extracellular alkalosis

Question 25

Lack of intracellular K leads to:

Answer 25

Increased excretion of H+ in exchange for sodium The production of an acid urine Generation of bicarbonate

Question 26

How does alkalosis lead to hypokalaemia?

Answer 26

low H+ → K+ shifted into cells → hypokalaemia

Question 27

Recall some causes of hypokalaemia

Answer 27

GRRR ## Footnote **GI loss** diarrhoea, vomiting, fistulas **Renal loss** mineralcorticoid excess (hyperaldosteronism, excess cortisol acts on aldosterone R) increased sodium delivery to distal nephrons osmotic diuresis renal tubular disease **Restribution into cells** insulin/insulinoma beta agonist alkalosis **Rare causes** renal tubular acidosis type 1+2 hypomagnesiaemia

Question 28

Recall cauess of cushing's syndrome

Answer 28

pituitary, ectopic ACTH, adrenal tumour

Question 29

How can pituitary-dependent Cushing's and ectopic ACTH be distinguished?

Answer 29

Pituitary petrosal sinus sampling

Question 30

What test is best to diagnose the cause of ectopic ACTH?

Answer 30

CXR CT thorax: Small lesion in hilum near mediastinum Very slow growing multiple mets (SCLC) CT abdomen: Bilateral adrenal hyperplasia Pathology: zona glomerulosa expanded Managed: Bilateral adrenalectomy

Question 31

What are some cauess of ectopic ACTH?

Answer 31

lung cancer (SCLC) other cancers

Question 32

If a patient has a high ACTH and very severe hypokalaemia, what is the most likely cause of the high ACTH?

Answer 32

Ectopic ACTH

Question 33

If HDDST shows failure of dexamethasone to suppress the axis then what is the cuase for the Cushing's syndrome?

Answer 33

extopic ## Footnote Pituitary disease would be suppressed by a high-dose test Adrenal tumours would suppress ACTH

Question 34

what electrolyte imbalance does Cushing's syndrome cause?

Answer 34

hypokalaemia * High levels ACTH → very high cortisol levels * High cortisol overpowers MR (overpowers inactivating enzyme) - aldosterone-like effect * Causes a K+ loss also hypotension due to severe hypokalaemia

Question 35

What ECG changes would you expect in an inferior MI?

Answer 35

ST elevation in leads II, III, aVF + reciprocal depression in V2

Question 36

Treatment for MI

Answer 36

Aspirin Beta blocker Thrombolysis/primary angioplasty GTN sublingual Pain relief