Clinical biochemistry and metabolism

6 Clinical biochemistry and metabolism


Between 60 and 70% of all critical decisions taken in regard to patients in health-care systems in developed countries involve a laboratory service or result. This chapter describes disorders whose primary manifestation is in abnormalities of biochemistry laboratory results, or whose underlying pathophysiology involves disturbance in specific biochemical pathways. Discussion of diabetes mellitus and other endocrine disorders is to be found in Chapters 10 and 11.



WATER AND ELECTROLYTE DISTRIBUTION


In a typical adult male, the 40 litres of total body water (TBW) constitute ∼60% of the body weight. More than half is located inside cells (the intracellular fluid or ICF), while the remainder is in the extracellular fluid (ECF) compartment. Of the ECF, the plasma is itself a small fraction (some 3 litres), while the remainder is interstitial fluid within the tissues but outside the cells.


The dominant cation in the ICF is potassium, while in the ECF it is sodium (Fig. 6.1). Phosphates and negatively charged proteins constitute the major intracellular anions, while chloride and, to a lesser extent, bicarbonate dominate the ECF anions. An important difference between the plasma and interstitial ECF is that only plasma contains significant concentrations of protein.



The major force maintaining the difference in cation concentration between the ICF and ECF is the sodium–potassium pump (Na,K-activated ATPase) integral to all cell membranes. Maintenance of the cation gradients across cell membranes is essential for many cell processes, including the excitability of conducting tissues such as nerve and muscle. The difference in protein content between the plasma and the interstitial fluid compartment is maintained by the protein permeability barrier at the capillary wall. This protein concentration gradient contributes to the balance of forces across the capillary wall favouring fluid retention within the capillaries (the colloid osmotic, or oncotic, pressure of the plasma), thus maintaining an adequate circulating plasma volume.




DISORDERS OF SODIUM BALANCE


When sodium balance is disturbed, as a result of imbalance between intake and excretion, any tendency for plasma sodium concentration to change is usually corrected by the osmotic mechanisms controlling water balance (see below). As a result, disorders in sodium balance present chiefly as altered ECF volume rather than altered sodium concentration.




SODIUM DEPLETION (USUALLY ASSOCIATED WITH HYPOVOLAEMIA)


Aetiology includes the following factors:











DISORDERS OF WATER BALANCE


Daily water intake can vary over a wide range, from 500 ml to several litres a day. While a certain amount of water is lost through the stool, sweat and the respiratory tract, the kidneys are chiefly responsible for adjusting water excretion to maintain a constant body water content and body fluid osmolality (normal range 280–300 mmol/kg).


Disturbances in body water metabolism, in the absence of changes in sodium balance, manifest principally as abnormalities of plasma sodium concentration, and hence of plasma osmolality. The main consequence of changes in plasma osmolality, especially when rapid, is altered cerebral function. This is because, when extracellular osmolality changes abruptly, water flows rapidly across cell membranes with resultant cell swelling (during hypo-osmolality) or shrinkage (during hyperosmolality). Cerebral cell function is very sensitive to such volume changes, particularly during cell swelling where an increase in intracerebral pressure occurs due to the constraints posed by the bony skull, resulting in impaired cerebral perfusion.




HYPONATRAEMIA


The causes of hyponatraemia (plasma Na <135 mmol/l) are best organised according to any associated change in ECF volume status, i.e. the total body sodium. In all cases, there is retention of water relative to sodium, and it is the clinical examination rather than the electrolyte test results which gives clues to the underlying problem.


Hypovolaemic (sodium deficit with a relatively smaller water deficit): Renal Na loss (diuretics), GI Na loss (vomiting, diarrhoea).


Euvolaemic (water retention alone, i.e. ‘dilutional’): Primary polydipsia, SIADH (Box 6.3).



Hypervolaemic (sodium retention with relatively greater water retention): Heart failure, cirrhosis, chronic kidney disease (without water restriction).






HYPERNATRAEMIA


Just as hyponatraemia represents a failure of the mechanisms for diluting the urine during free access to water, so hypernatraemia (plasma Na > 150 mmol/l) reflects an inadequacy of the kidney in concentrating the urine in the face of relatively restricted water intake. Similar to hyponatraemia, the causes of hypernatraemia may be classified based on the volume state of the patient.


Hypovolaemic (sodium deficit with a relatively greater water deficit): Renal Na losses (diuretics), GI Na losses (colonic diarrhoea), skin Na losses (excessive sweating).


Euvolaemic (water deficit alone): Diabetes insipidus (central or nephrogenic, p. 377).


Hypervolaemic (sodium retention with relatively less water retention): Enteral or parenteral nutrition, oral salt administration, chronic kidney disease (during water restriction).



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Apr 3, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Clinical biochemistry and metabolism

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