Hyperuricaemia

and electrolyte disorders

Dr Francesca Mazzacuva

1
Objectives
• Review metabolism of purines and production of uric acid
• Dysfunctions of uric acid’s production
• Gout
• Electrolytes and the role of membrane permeability
• Sodium imbalances
• Potassium imbalances
Purines
Multiple functions:
Nucleotides: ATP GTP

Energy molecules: ATP

Component of nucleic acids
Signaling molecules: ATP, GTP

Homeostasis of purines is relevant to many functions

PATHWAY PURINES:
Multiple sources

Metabolic “recycle”

Multiple molecules

Single catabolic product:

URIC ACID
Monosodium urate is the salt of uric
acid (more soluble)

IMP: inosinic acid, first purine formed by de novo synthesis;

Precursor of AMP, GMP and hypoxanthines

Monosodium urate poor solubility

higher solubility
 Hyperuricaemia
(measured in plasma)

Overproduction of Uric acid

Primary causes no influences from external Secondary causes

factors

(increase in plasma) (increase in body)

- Inherited metabolic - Excess nutrition

diseases - Increased ATP metabolism
- Cytotoxic drugs
- Idiopathic (unknown) - Alcohol
 Hypouricaemia
(measured in plasma)

Decreased secretion of Uric acid

Primary causes Secondary causes
(decrease in plasma) (decrease in body)

- Idiopathic (unknown) - Renal Disease/failure

- Hypertension
- Thiazide diuretics
- Salicylate
Inherited disorders of purine metabolism
 Gout
is well known to be associated with hyperuricaemia

Increase in
uric acid
in serum

Accumulation of crystals in
joint (synovial fluid)
Diagnosis of Gout
- Synovial fluid sample  microscopy : birefringence of crystals
- Uric acid in serum
- Family history
 Gout

Purines are important metabolites that need to be regulated to maintain good

physiological functions

https://www.verywellhealth.com/hyperuricemia-high-uric-acid-189838
 Electrolytes
They can have positive or negative charges; they occur naturally in the body and control
important physiologic functions.

Na+
Cl-
K+
HCO3-
Optimum concentration range in blood

Ca2+
SO42+
Mg2+
PO43-
 Water homeostasis

Osmolality is a measure of the number of osmotically

active solute particles dissolved in a Kg of
solvent (water in biological systems). These osmotically
active substances increase osmolality of a fluid and
cause solvent (water) to move across membranes. It is
expressed as mOsm/Kg
urine, sweeting,
breathing...
 Water homeostasis

Osmolality (sum of the concentrations of the solutes in a

liquid) needs to be maintained. Water can cross
membranes keeping optimal osmolality.
 Semi-permeable cell membrane
Water can cross cellular membranes but ions cannot. Water cross the membranes to maintain
optimal ions concentration

H2O H 2O
Cl- Na+
Na +

K
K+
+
Cl -
INTRACELLULAR SPACE ETRACELLULAR SPACE

2K+ ATP ATP pumps maintain the gradient

of electrolytes (pumping them

ase against their concentration

3Na+ gradient) e.g. Na+/K+ ATPase

How is the water balance maintained?

Increased plasma osmolality triggers

various responses in the brain
 How is the water balance maintained?

Increased plasma osmolality triggers

various responses in the brain

- REGULATION of WATER INTAKE:

THIRST

https://pressbooks-dev.oer.hawaii.edu/humannutrition/chapter/regulation-of-water-balance/
 How is the water balance maintained?

Increased plasma osmolality triggers various

responses in the brain

- REGULATION of WATER INTAKE:

THIRST

- REGULATION of WATER OUTPUT:

hormonal pathway ADH (antidiuretic
hormone)

https://pressbooks-dev.oer.hawaii.edu/humannutrition/chapter/regulation-of-water-balance/
 How is the water balance maintained?
- REGULATION of WATER
INTAKE: THIRST

- REGULATION of WATER
OUTPUT: hormonal
pathway ADH (antidiuretic
hormone)
How is the water balance maintained?
Electrolyte measurements
• Essential aspect to monitor in many conditions
• Electrolytes can be measured using ion-selective
electrodes (however, the optimal range of each ion is narrow, and it is easy to get
contamination from other compounds during the measurement. Moreover, it is important to
look at the status of cells quickly)

• Important to consider possible contamination (e.g.

anticoagulants)

• Generally reported in mmoL

Disturbance of plasma sodium (Na+)

Hyponatraemia 135
Normal
- 145 mM
Hypernatraemia
 Hyponatraemia
can happen when there is low fluid volume but also high fluid volume in the body

(they are involved in Na+ retention)

(water intake> and consequently water output >; Na +
depletion with urination)
(patients monitored for Na+)

(they are a class of steroid hormones that regulate salt and water
balances. Aldosterone is the primary mineralocorticoid.
Mineralocorticoids promote Na+ and K+ transport, usually
followed by changes in water balance)
Syndrome of inappropriate antidiuretic hormone
(SIADH)
• Characteristics
• Lower plasma osmolarity (<270 mOsm/Kg)
• Higher urinary osmolarity (>100mOsm/Kg)
Due to leakage of sodium in urine while euvolaemia
• Causes
• ADH production continues despite low osmolality

• Management (of hyponatraemia)

• Restriction of fluids
• Supplement of NaCl
It must be gradual (depends on suspected cause)
 Hyponatraemia

normal serum sodium

concentration range:
135 - 145 mM

https://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2011.72.Sup2.M22
https://clinicaltoolkit.scot.nhs.uk/adult-medical-emergency-handbook/ame-handbook/renal-metabolic-and-endocrine-emergencies/assessment-and-management-of-a-patient-with-hyponatraemia/
 Hypernatraemia
• More rare
• Generally due to water level rather than total Na+

Diabetes insipidus
• Symptom
• High urine volume

• Causes
• Cranial: reduced release of ADH (ADH reabsorbes water)
• Nephrogenic: reduced sensitivity to ADH
 Diabetes insipidus

ADH is synthesised in neuronal cell bodies and released into the posterior pituitary

- Cranial diabetes insipidus: ADH deficiency from posterior pituitary (large volumes of
diluted urine, dehydration). 30% idiopathic causes

- Nephrogenic diabetes insipidus: nephron ADH insensitivity

Large production of urine

ADH
Thirst
H2 0
Dehydration
Distinguish cranial from nephrogenic diabetes insipidus
water deprivation test and DDAVP (desmopressin) test

Restrict drinking up to 7 hours (under close medical control)

Diabetes insipidus Control ranges
Blood osmolarity > 295 mOsm/Kg 285 - 295 mOsm/Kg
Urine osmolarity < 700 mOsm/Kg > 700 mOsm/Kg

Treat with desmopressin (ADH analogue)

Cranial Nephrogenic (kidneys unresponsive)
Urine osmolarity > 700 mOsm/Kg Urine osmolarity < 700 mOsm/Kg

Cranial diabetes insipidus: reduced release of ADH (ADH reabsorbes water)

Nephrogenic diabetes insipidus: reduced sensitivity to ADH
 Potassium disturbances
(K+)

Hypokalaemia Normal
3.5 – 5.1 mM
Hyperkalaemia

High K+ levels lead to muscle disturbances especially cardiac muscle

Hypokalemia
• Increase K+ loss by kidney
• Increase K+ loss by GI tract
• Redistribution extra  intracellular K+
e.g. Thiazide diuretics (commonly used to treat high blood
pressure and heart failure) reduce Na+ re-absorption by the kidney
 Na+ from cells is exchanged for K+ leading to hypokalaemia

Hyperkalemia
Causes
• Release K+ from cells (e.g. cell damage)
• Impaired K+ excretion
Symptoms of AKI
Osmolar gap
• Osmolality can be calculated (approximated) using following formula:
2x[Na+] + [K+] + [urea]+ [glucose] (mM)

• Osmolality can also be directly measured by an osmometer (measures

freezing point of the fluid; higher osmolality=lower freezing point)

1. The difference between calculated and measured osmolality is referred to

osmolar gap:
measured osmolality – calculated osmolarity < 10

• If > 0, it indicates the presence of other compounds that are contributing

to osmolality e.g. poisons (toxins, alcohol, etc.) or diuretics (mannitol)
Osmolar gap is different from anion gap

• Osmolar gap = measured osmolality – calculated osmolarity

• Anion gap = [Na+] + [K+] – [Cl-] – [HCO3-]

Anion gap is characteristic of metabolic acidosis.
Metabolic acidosis is the build-up of acid in the body due to
kidney disease or kidney failure.
 Summary
• Measurement of uric acid and electrolytes is part of standard laboratory
investigations and need to be analysed in the context of the patient’s
condition

• AKI can lead to the accumulation of water, sodium, and other metabolic
products. It can also result in several electrolyte disturbances. It is a very
common condition, especially among hospitalized patients