Metabolic Acidosis

Dr Daniel ZamanfarDr Daniel ZamanfarPediatric s Endocrinologist

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Metabolic acidosis is a very common symptom in pediatrics.

It can be observed in a large variety of aquiredIt can be observed in a large variety of aquiredcircumstances including:

Infections severs catabolic states tissueInfections, severs catabolic states, tissue anoxia, severe dehydration and intoxication.

All these common causes should be ruled out before considering IEMs.

It must be stressed that these circumstances can also sometimes trigger acute ggdecompensation for an unrecognized IEM.

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Metabolic acidotic states in pediatric patients are understood mainly on the basis of simultaneous determinations of blood gases, electrolytes and anion gap, glucose, lactate, pyruvate, ketone bodies and amonia.At the bedside, the physician should chech for a special odor and for ketonuria and α- ketoaciduria(DNPH reaction), and should measure urine PH and electrolytes.Urine and plasma samples should be frozen for subsequent metabolic investigations(mostly of amino acides and organic acids).

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As usual, it is important to collect allAs usual, it is important to collect all

laboratory data at the same time and, if

possible, before therapy.

Therapy can mask some significant symptomsTherapy can mask some significant symptoms.

When disease is advanced, nonspecific

abnormalities can mask the primary problem.

Such as respiratory acidosis, severe

hypelactacidemia or secondary hypermonemia)

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The presence or absence of ketonuriaThe presence or absence of ketonuria

associated with MA is the major clinical key to

the diagnosis, particularly in the neonetal

periodperiod.

During which significant ketonuria is nearly

pathognomonic of an IEM.

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MA without ketosis:

PDH deficiency

FAODFAOD

Some disorders of gluconeogensis (Particularly

when there is moderate to severe hyper

lactacidemia)

All these disorders except PDH deficency have

concomitant fasting hypoglycemia.

Although fructose diphosphatase and glucose-6-

phosphatase deficiencies are classically considered tophosphatase deficiencies are classically considered to

give rise to ketoacidosis, it may be moderate or absent.٧

MA with a NL AG and without hyperlactacidemia or hypoglycemia:

The most frequent diagnosis is RTA type I or IIq g yp

Presents with significant hyperchloremia and alkaline urine (PH>8)urine (PH>8).

In RTA II, urinary PH is < 5 when the patient is f dl id tiprofoundly acidotic.

Pyro glutamic aciduria can also present early in life with constant, isolated MA, which can be mistaken for RTA II.

The AG is slightly increased and the urinary PH is <5.

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MA associated with ketosis(ketoacidotic

states)

C th d l f IEMSCompose the second large group of IEMS.

The serum concentration of ketone bodies

represents the balane between their

production by the liver and their utilizationproduction by the liver and their utilization

by peripheral tissues.

Th f k t b dThe range of serum ketone body

concentration varies with age and

nutritional state.٩

Many metabolic disorders of childhood may lead to k t id i i l diketoacidosis, including:

1) Insulin dependent diabetes.

2) Inborn errors of branched-chain amino acid metabolism,

The most frequent are: the late-onset forms of MSUD and MMA, PA and IVA.

3) Congenital lactic acidosis such as multiple carboxylase and pyruvate carboxylase deficiencies.

4) Inherited defects in enzymes of gluconeogenesis glucose-6-phosphatase, fructose 1,6-diphosphatase) and of glycogen synthesis(glycogen synthase). ١٠

5) The ketolytic defects represented by the

succinyl CoA transferase, 3-ketothiolase, and

acetoacetyl CoA thiolase deficenciesacetoacetyl CoA thiolase deficencies.

In the first four categories of disorders, hyper

ketosis is thought to be related mainly to an

excess of ketone body production.

In contrast, ketotic ststes due to ketolytic defects

are mainly caused by decreased peripheralare mainly caused by decreased peripheral

ketone body utilazation.

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When MA is associated with ketosis, the first

parameter to be considered is the glucose level

Can be elevated NL or lowCan be elevated, NL or low.

When ketoacidosis is associated with

hyperglycemia, the classic diagnosis is DKA.

OA such as MMA or IVA and ketolytic defects can

also be associated with hyperglycemia and

glycosuria, mimicking diabetes.glycosuria, mimicking diabetes.

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The distinction between these conditions is

based on ammonia and lactate levels.

Are generally rocreased in OAsAre generally rocreased in OAs

Are generally NL or low in ketolytic defects.

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When ketoacidosis is associated with h l ihypoglycemia:

The first classic group of diseases to be considered is the gluconeogenesis and glycogenolysis defects.

The main symptoms suggestive of this group of disorders are hepatomegaly and hyper p g y yplactacidemia

How ever these are not constant findingsHow ever, these are not constant findings.

When there is not significant hepatomegaly, late onset forms of MSUD and of OAs must belate-onset forms of MSUD and of OAs must be considered as well.

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Short – chain acyl CoA dehydrogenase can present y y g p

with KA and normoglicemia either in the neonatal

period or during recurrent attacks in infancyperiod or during recurrent attacks in infancy.Affected patients do not consistently excrete characteristic metabolites which some timecharacteristic metabolites, which some time renders the diagnosis difficult.

A classic possibility in the differential diagnosis isA classic possibility in the differential diagnosis is

adrenal insufficiency, which can strike as a

ketoacidotic attack with hypoglicemia.

When blood glucose levels are NL, congenital lactic g g

acidosis also must be considered.١۵

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