Chemical Pathology EMQs Flashcards
Sodium handling
A Ethanol
B SIADH
C Frusemide
D Chronic kidney disease
E Conn’s syndrome
F Diarrhoea
G Congestive cardiac failure
H Addison’s disease
I Hyperlipidaemia
A 50-year-old woman with known diabetes has a routine blood test which demonstrates the following: Na 130 (135–145 mmol/L) K 4.1 (3.5–5.0 mmol/L) Urea 4.2 (3.0–7.0 mmol/L) Glucose 3.1 (2.2–5.5 mmol/L) Osmolality 283 (275–295 mOsm/kg)
I Hyperlipidaemia
Pseudo-hyponatraemia can occur in patients with hyperlipidaemia
(I) or hyperproteinaemia. In such states, lipids and proteins will
occupy a high proportion of the total serum volume. Although the
sodium concentration
in serum water is in fact normal, a lower
sodium concentration
will be detected due to dilution by increased
lipids and protein molecules. As a consequence, there is an apparent
hyponatraemia.
A spurious result due to the sample being taken from
the drip arm can also cause pseudo-hyponatraemia.
Sodium handling
A Ethanol
B SIADH
C Frusemide
D Chronic kidney disease
E Conn’s syndrome
F Diarrhoea
G Congestive cardiac failure
H Addison’s disease
I Hyperlipidaemia
A 45-year-old man is seen by his specialist. His last blood and urine tests demonstrated the following: Na 129 (135–145 mmol/L) K 5.5 (3.5–5.0 mmol/L) Urea 8.2 (3.0–7.0 mmol/L) Glucose 4.2 (2.2–5.5 mmol/L) Osmolality 265 (275–295 mOsm/kg) Urine osmolality 26 mOsm/kg
D Chronic kidney disease
A true hyponatraemic state occurs when the osmolality is simultaneously
low. Chronic kidney disease (CKD; D) results in urinary protein
loss and hence oedema. A reduced circulating volume causes activation
of the renin–angiotensin system, thereby raising blood sodium levels.
This in turn causes release of antidiuretic hormone (ADH) from the
posterior pituitary leading to water retention and hypervolaemic
hyponatraemia. Water reabsorption in the renal tubules increases urine
osmolality (>20 mmol/L indicates a renal cause of hyponatraemia). CKD
is also associated with hyperkalaemia and azotaemia.
Sodium handling
A Ethanol
B SIADH
C Frusemide
D Chronic kidney disease
E Conn’s syndrome
F Diarrhoea
G Congestive cardiac failure
H Addison’s disease
I Hyperlipidaemia
A 30-year-old woman visits her GP due to pigmentation of her palmar creases. Two weeks later the following blood and urine tests are received: Na 128 (135–145 mmol/L) K 5.9 (3.5–5.0 mmol/L) Urea 5.2 (3.0–7.0 mmol/L) Glucose 1.8 (2.2–5.5 mmol/L) Osmolality 264 (275–295 mOsm/kg) Urine osmolality 24 mOsm/kg
H Addison’s disease
Addison’s disease (H) is also known as primary adrenal insufficiency
(reduced aldosterone and cortisol); consequently there is a rise in the
production of adrenocorticotropic hormone (ACTH). An impaired synthesis
of aldosterone reduces reabsorption of sodium and increases
excretion of potassium in the distal convoluted tubule and collecting
ducts of the kidney; this leads to a simultaneous hyponatraemia and
hyperkalaemia. Reduced cortisol production causes hypoglycaemia due
to impaired gluconeogenesis. Clinical features of Addison’s disease
include hyperpigmentation, postural hypotension and weight loss.
Sodium handling
A Ethanol
B SIADH
C Frusemide
D Chronic kidney disease
E Conn’s syndrome
F Diarrhoea
G Congestive cardiac failure
H Addison’s disease
I Hyperlipidaemia
A 30-year old woman is seen by her GP after a 5-day episode of productive
cough and lethargy. The GP notes dullness on percussion of the patient’s left
lower lung. Blood and urine tests reveal the following:
Na 128 (135–145 mmol/L)
K 4.1 (3.5–5.0 mmol/L)
Urea 3.5 (3.0–7.0 mmol/L)
Glucose 3.2 (2.2–5.5 mmol/L)
Osmolality 265 (275–295 mOsm/kg)
Urine osmolality 285 mOsm/kg
B SIADH
The syndrome of inappropriate ADH secretion (B; SIADH) results from
the excess release of ADH. In this case the clinical features suggest
pneumonia is the cause, but the aetiologies of SIADH are numerous,
including malignancy, meningitis and drugs (carbamazepine). Criteria
to diagnose SIADH include the following:
• Hyponatraemia 100 mmol/L
• High urine sodium >20 mmol/L
• Euvolaemia
• No adrenal, renal or thyroid dysfunction
Characteristically the urine osmolality is inappropriately high; in normal
circumstances if the plasma osmolality is low, the urine osmolality
will stop rising as reduced ADH secretion prevents water retention. As
a rule of thumb in SIADH, urine osmolality is greater than plasma
osmolality.
Sodium handling
A Ethanol
B SIADH
C Frusemide
D Chronic kidney disease
E Conn’s syndrome
F Diarrhoea
G Congestive cardiac failure
H Addison’s disease
I Hyperlipidaemia
A 63-year-old man with chronic obstructive pulmonary disease (COPD) sees his GP due to oedematous ankles. His blood and urine tests show the following: Na 130 (135–145 mmol/L) K 4.4 (3.5–5.0 mmol/L) Urea 4.2 (3.0–7.0 mmol/L) Glucose 3.1 (2.2–5.5 mmol/L) Osmolality 268 (275–295 mOsm/kg) Urine osmolality 16–mmol/LmOsm/kg
G Congestive cardiac failure
Congestive cardiac failure (G) may present with shortness of breath, pitting
peripheral oedema and/or raised jugular venous pulse (JVP). In this
scenario, shortness of breath may be masked by the patient’s COPD.
The clinical picture together with the blood result demonstrating a low
sodium and low osmolality suggest a hypervolaemic hyponatraemia.
This scenario can be differentiated from hypervolaemia as a result of
CKD (D) by the urine osmolality, which is less than 20 mmol/L in this
instance, thereby suggesting a non-renal cause for the hyponatraemia
Ethanol (A) may cause hyponatraemia in the context of a raised plasma
osmolality (>295 mmol/L). Other low molecular weight solutes that can
cause hyponatraemia (when osmolality is raised) include mannitol and
glucose.
Frusemide (C) and other diuretics cause a hypovolaemic hyponatraemia.
As well as a low plasma sodium and osmolality, the urine osmolality will
be greater than 20 mmol/L, signifying a renal cause of hyponatraemia.
Conn’s syndrome (E), also known as primary aldosteronism, results
from an aldosterone-producing adenoma producing excess aldosterone.
Biochemical (and concurrent clinical) features include hypernatraemia
(hypertension) and hypokalaemia (paraesthesia, tetany and weakness).
Diarrhoea (F) leads to a hypovolaemic hyponatraemia (as does vomiting).
Plasma sodium and osmolality will be low and urine osmolality
will be lower than 20 mmol/L indicating an extra-renal cause of
hyponatraemia.
Potassium handling
A Spurious sample
B Anorexia
C Diarrhoea
D Renal tubular acidosis
E Insulin overdose
F Bartter syndrome
G Frusemide
H Renal failure
I ACE inhibitors
A 15-year-old boy presents to accident and emergency with loss of consciousness. His blood sugars are found to be extremely low. Blood tests demonstrate the following: Na 138 (135–145 mmol/L) K 3.0 (3.5–5.0 mmol/L) Urea 4.2 (3.0–7.0 mmol/L) Creatinine 74 (60–120 mmol/L) pH 7.48 (7.35–7.45) HCO3 31 (22–28 mmol/L)
E Insulin overdose
Insulin overdose (E) in a diabetic patient will cause a redistributive
hypokalaemia and concurrent metabolic alkalosis. Insulin causes a shift
of potassium ions from the extracellular space to the intracellular space,
thereby lowering blood potassium levels. Metabolic alkalosis can also
cause a redistributive hypokalaemia; a reduced hydrogen ion concentration
in the blood causes increased intracellular hydrogen ion loss to increase
extracellular levels via Na+/H+ ATPase; potassium ions therefore diffuse
intracellularly to maintain the electrochemical potential. Adrenaline and
re-feeding syndrome also cause redistributive hypokalaemia.
Potassium handling
A Spurious sample
B Anorexia
C Diarrhoea
D Renal tubular acidosis
E Insulin overdose
F Bartter syndrome
G Frusemide
H Renal failure
I ACE inhibitors
A 64-year-old man who is an inpatient on the Care of the Elderly ward is found to have the following blood results: Na 136 (135–145 mmol/L) K 5.5 (3.5–5.0 mmol/L) Urea 14.4 (3.0–7.0 mmol/L) Creatinine 165 (60–120 mmol/L) pH 7.44 (7.35–7.45) HCO3 27 (22–28 mmol/L)
H Renal failure
Renal failure (H) can lead to hyperkalaemia secondary to reduced
distal
renal delivery of sodium ions. As a consequence, there is
reduced exchange of potassium ions via the Na/K ATPase pump in
the collecting
duct, which thereby leads to accumulation of potassium
ions in the blood and hence hyperkalaemia. An increase in aldosterone
release will initially cause a compensatory loss of potassium ions;
as renal failure progresses, this homeostatic mechanism will become
decompensated and hyperkalaemia will result. Renal failure will also
be reflected in the deranged urea and creatinine levels due to reduced
excretion.
Potassium handling
A Spurious sample
B Anorexia
C Diarrhoea
D Renal tubular acidosis
E Insulin overdose
F Bartter syndrome
G Frusemide
H Renal failure
I ACE inhibitors
A 16-day-old baby girl is found to have low blood pressure. Urinary calcium levels are found to be elevated. Blood tests demonstrate the following results: Na 138 (135–145 mmol/L) K 2.8 (3.5–5.0 mmol/L) Urea 3.4 (3.0–7.0 mmol/L) Creatinine 62 (60–120 mmol/L) pH 7.51 (7.35–7.45) HCO3 33 (22–28mmol/L)
F Bartter syndrome
Bartter syndrome (F) is an autosomal recessive condition due to a defect
in the thick ascending limb of the loop of Henle. It is characterized by
hypokalaemia, alkalosis and hypotension. The condition may also lead
to increased calcium loss via the urine (hypercalcuria) and the kidneys
(nephrocalcinosis). Various genetic defects have been discovered; neonatal
Bartter syndrome is due to mutations in either the NKCC2 or ROMK
genes. In the associated milder Gitelman syndrome, the potassium transporting
defect is in the distal convoluted tubule of the kidney.
Potassium handling
A Spurious sample
B Anorexia
C Diarrhoea
D Renal tubular acidosis
E Insulin overdose
F Bartter syndrome
G Frusemide
H Renal failure
I ACE inhibitors
A 32-year-old man presents to his GP for a check-up. His serum aldosterone is found to be low. Blood tests reveal the following: Na 140 (135–145 mmol/L) K 5.6 (3.5–5.0 mmol/L) Urea 5.3 (3.0–7.0 mmol/L) Creatinine 92 (60–120 mmol/L) pH 7.38 (7.35–7.45) HCO3 24 (22–28 mmol/L)
I ACE inhibitors
ACE inhibitors (I) will lead to hyperkalaemia due to reduced potassium
excretion. ACE inhibitors antagonize the effect of angiotensin converting
enzyme, the enzyme which catalyzes the production of angiotensin
II from angiotensin I. A decreased level of angiotensin II reduces the
production of aldosterone in the adrenal glands, a key hormone causing
the excretion of potassium. Other causes of reduced excretion of potassium
include Addison’s disease, renal failure and potassium sparing
diuretics.
Potassium handling
A Spurious sample
B Anorexia
C Diarrhoea
D Renal tubular acidosis
E Insulin overdose
F Bartter syndrome
G Frusemide
H Renal failure
I ACE inhibitors A 68-year-old woman on the Care of the Elderly ward is found to have the following blood results: Na 138 (135–145 mmol/L) K 3.0 (3.5–5.0 mmol/L) Urea 4.2 (3.0–7.0 mmol/L) Creatinine 74 (60–120 mmol/L) pH 7.31 (7.35–7.45) HCO3 28 (22–28 mmol/L)
D Renal tubular acidosis
Renal tubular acidosis (D) occurs when there is a defect in hydrogen
ion secretion into the renal tubules. Potassium secretion into the renal
tubules therefore increases to balance sodium reabsorption. This results
in hypokalaemia with acidosis. Renal tubular acidosis is classified
according to the location of the defect: type 1 (distal tubule), type 2
(proximal tubule), type 3 (both distal and proximal tubules). Type 4
results from a defect in the adrenal glands and is included in the classification
as it results in a metabolic acidosis and hyperkalaemia.
Acid–base balance A Metabolic acidosis B Metabolic acidosis with respiratory compensation C Metabolic alkalosis D Metabolic alkalosis with respiratory compensation E Respiratory acidosis F Respiratory acidosis with metabolic compensation G Respiratory alkalosis H Respiratory alkalosis with metabolic compensation I Mixed metabolic and respiratory acidosis
pH 7.31 (7.35–7.45)
pO2 7.6 (10.6–13 kPa)
pCO2 8.2 (4.7–6.0 kPa)
HCO3 26 (22–28 mmol/L)
E Respiratory acidosis
Respiratory acidosis (E) is defined by a low pH (acidosis) together with
a high pCO2, due to carbon dioxide retention secondary to a pulmonary,
neuromuscular or physical causes. There is no metabolic compensation
in this case, suggesting this is an acute pathology; a compensatory
metabolic rise in HCO3 from the kidneys can take hours or days.
This patient is also hypoxic with a low pO2. Causes of an acute respiratory
acidosis include an acute exacerbation of asthma, foreign body
obstruction and cardiac arrest.
Acid–base balance A Metabolic acidosis B Metabolic acidosis with respiratory compensation C Metabolic alkalosis D Metabolic alkalosis with respiratory compensation E Respiratory acidosis F Respiratory acidosis with metabolic compensation G Respiratory alkalosis H Respiratory alkalosis with metabolic compensation I Mixed metabolic and respiratory acidosis
pH 7.36 (7.35–7.45)
pO2 14.2 (10.6–13 kPa)
pCO2 4.1 (4.7–6.0 kPa)
HCO3 14 (22–28 mmol/L)
B Metabolic acidosis with
respiratory compensation
Metabolic acidosis with respiratory compensation (B) occurs when pH
is low (acidosis) and HCO3 is low with concurrent respiratory compensation
by decreasing pCO2. The anion gap can differentiate between
causes of metabolic acidosis (anion gap = [Na++ K+] – [Cl−+ HCO3
−];
normal range between 10 and 18 mmol/L). Causes of a raised anion gap
can be remembered by the mnemonic MUDPILES: methanol/metformin,
uraemia, diabetic ketoacidosis, paraldehyde, iron, lactate, ethanol and
salicylates. Causes of a normal anion gap include diarrhoea, Addison’s
disease and renal tubular acidosis.
Acid–base balance A Metabolic acidosis B Metabolic acidosis with respiratory compensation C Metabolic alkalosis D Metabolic alkalosis with respiratory compensation E Respiratory acidosis F Respiratory acidosis with metabolic compensation G Respiratory alkalosis H Respiratory alkalosis with metabolic compensation I Mixed metabolic and respiratory acidosis
pH 7.45 (7.35–7.45)
pO2 10.2 (10.6–13 kPa)
pCO2 7.2 (4.7–6.0 kPa)
HCO3 32 (22–28 mmol/L)
D Metabolic alkalosis with
respiratory compensation
Metabolic alkalosis with respiratory compensation (D) occurs when pH is
high (alkalosis) and HCO3 is high with a compensatory reduction in respiratory
effort that increases pCO2. As respiratory effort is reduced there
is the possibility of the patient becoming hypoxic. Causes of metabolic
alkalosis include vomiting, potassium depletion secondary to diuretic
use, burns and sodium bicarbonate ingestion. Respiratory compensation
increase serum CO2 concentration, which reduces pH back towards normal.
Acid–base balance A Metabolic acidosis B Metabolic acidosis with respiratory compensation C Metabolic alkalosis D Metabolic alkalosis with respiratory compensation E Respiratory acidosis F Respiratory acidosis with metabolic compensation G Respiratory alkalosis H Respiratory alkalosis with metabolic compensation I Mixed metabolic and respiratory acidosis
pH 7.30 (7.35–7.45)
pO2 8.2 (10.6–13 kPa)
pCO2 7.2 (4.7–6.0 kPa)
HCO3 19 (22–28 mmol/L)
I Mixed metabolic and respiratory
acidosis
Mixed metabolic and respiratory acidosis (I) occurs when there is a
low pH and a simultaneous high pCO2 and low HCO3. In the case of a
mixed metabolic and respiratory acidosis, the metabolic acidosis component
may be due to conditions such as uraemia, ketones produced as
a result of diabetes mellitus or renal tubular acidosis. The respiratory
acidosis component may be due to any cause of respiratory failure.
Hence, this mixed picture may occur in a COPD patient with concurrent
diabetes mellitus.
Acid–base balance A Metabolic acidosis B Metabolic acidosis with respiratory compensation C Metabolic alkalosis D Metabolic alkalosis with respiratory compensation E Respiratory acidosis F Respiratory acidosis with metabolic compensation G Respiratory alkalosis H Respiratory alkalosis with metabolic compensation I Mixed metabolic and respiratory acidosis
pH 7.49 (7.35–7.45)
pO2 13.6 (10.6–13 kPa)
pCO2 4.1 (4.7–6.0 kPa)
HCO3 23 (22–28 mmol/L)
G Respiratory alkalosis
Respiratory alkalosis (G) is biochemically defined by a raised pH (alkalosis)
and reduced pCO2. As previously mentioned, metabolic compensation
can take hours or days to occur. The primary pathology causing
respiratory alkalosis is hyperventilation which causes increased CO2 to be lost via the lungs. Causes of hyperventilation may be due to central
nervous system disease, for example stroke. Other causes of hyperventilation
include anxiety (panic attack), pulmonary embolism and drugs
(salicylates).
Liver function tests A Alcohol abuse B Gilbert’s syndrome C Gallstones D Dublin–Johnson syndrome E Non-alcoholic fatty liver disease F Crigler–Najjar syndrome G Alcoholic liver disease H Paracetamol poisoning I Hepatocellular carcinoma
AST 65 (3–35 IU/L) ALT 72 (3–35 IU/L) GGT 82 (11–51 IU/L) ALP 829 (35–51 IU/L) Total bilirubin 234 (3–17 μmol/L) Conjugated bilirubin 63 (1.0–5.1 μmol/L)
C Gallstones
Gallstones (C) may be composed of cholesterol, bilirubin or mixed in
nature. The major complication of gallstones is cholestasis, whereby
the flow of bile is blocked from the liver to the duodenum. This results
in right upper quadrant abdominal pain, nausea and vomiting. Other
causes of cholestasis include primary biliary cirrhosis, primary sclerosing
cholangitis and abdominal masses compressing the biliary tree.
Biochemically, cholestasis is defined by rises in GGT and ALP (obstructive
picture) that are greater than the rises in AST and ALT.
Liver function tests A Alcohol abuse B Gilbert’s syndrome C Gallstones D Dublin–Johnson syndrome E Non-alcoholic fatty liver disease F Crigler–Najjar syndrome G Alcoholic liver disease H Paracetamol poisoning I Hepatocellular carcinoma
AST 32 (3–35 IU/L) ALT 29 (3–35 IU/L) GGT 34 (11–51 IU/L) ALP 53 (35–51 IU/L) Total bilirubin 36 (3–17 μmol/L) Conjugated bilirubin 3.4 (1.0–5.1 μmol/L)
B Gilbert’s syndrome
Gilbert’s syndrome (B) is an autosomal dominant condition in which
there is a mutation in the enzyme UDP glucuronosyl transferase which
reduces conjugation of bilirubin in the liver. As a consequence patients
experience mild, intermittent jaundice. Jaundice in patients with
Gilbert’s syndrome may be precipitated by infection or starved states.
Biochemistry will reveal that all liver function tests are normal apart
from an isolated raised unconjugated bilirubin level, while conjugated
bilirubin is within the normal range.
Liver function tests A Alcohol abuse B Gilbert’s syndrome C Gallstones D Dublin–Johnson syndrome E Non-alcoholic fatty liver disease F Crigler–Najjar syndrome G Alcoholic liver disease H Paracetamol poisoning I Hepatocellular carcinoma
AST 1259 (3–35 IU/L) ALT 1563 (3–35 IU/L) GGT 73 (11–51 IU/L) ALP 46 (35–51 IU/L) Total bilirubin 15.2 (3–17 μmol/L) Conjugated bilirubin 4.2 (1.0–5.1 μmol/L)
E Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD; E) is due to fatty deposits
in the liver (steatosis), but where the underlying cause is not due to
alcohol. In such circumstances, aetiological factors include obesity,
diabetes, parenteral feeding and inherited metabolic disorders (glycogen
storage disease type 1). NAFLD may present with right upper quadrant
pain or may be asymptomatic. Liver function tests will reveal raised
AST and ALT levels (AST:ALT ratio
Liver function tests A Alcohol abuse B Gilbert’s syndrome C Gallstones D Dublin–Johnson syndrome E Non-alcoholic fatty liver disease F Crigler–Najjar syndrome G Alcoholic liver disease H Paracetamol poisoning I Hepatocellular carcinoma
AST 2321 (3–35 IU/L) ALT 2562 (3–35 IU/L) GGT 62 (11–51 IU/L) ALP 182 (35–51 IU/L) Total bilirubin 14 (3–17 μmol/L) Conjugated bilirubin 3.4 (1.0–5.1 μmol/L)
H Paracetamol poisoning
Paracetamol poisoning (H) is a common cause of acute liver failure. The
clinical features of acute liver failure reflect the diminished synthetic
and metabolic functioning of the liver. Characteristics include reduced
blood sugar level, metabolic acidosis, increased tendency to bleed and
hepatic encephalopathy. Biochemical tests will reveal AST and ALT levels
greater than 1000 IU/L. AST and ALT levels will be greater than GGT
and ALP levels, reflecting the hepatic rather than obstructive picture of
the pathology.
Liver function tests A Alcohol abuse B Gilbert’s syndrome C Gallstones D Dublin–Johnson syndrome E Non-alcoholic fatty liver disease F Crigler–Najjar syndrome G Alcoholic liver disease H Paracetamol poisoning I Hepatocellular carcinoma
AST 34 (3–35 IU/L) ALT 32 (3–35 IU/L) GGT 134 (11–51 IU/L) ALP 123 (35–51 IU/L) Total bilirubin (3–17 μmol/L) Conjugated bilirubin (1.0–5.1 μmol/L)
A Alcohol abuse
Alcohol abuse (A) can lead to deranged liver function tests. In the
absence of underlying liver disease, biochemical investigation may
demonstrate an isolated rise in GGT. There may also be mild elevations
in AST and ALT, reflecting mild hepatic damage. Haematology results
will show a macrocytic picture due to toxic effects of alcohol on the
bone marrow. Isolated raised GGT levels may also occur due to the
consumption of enzyme-inducing drugs such as phenytoin, carbamazepine
and phenobarbitone.
