Glucose Production
Glucose intake is not required for immediate energy needs is converted into glycogen, stored in the liver, heart and skeletal muscle. During fasting glycogen is broken down and released by the liver by glycogenesis. The infants ability varies by growth an
How can glucose be metabolized in the body?
production of energy
storage of glycogen
conversion to gluconeogenic precursors
How is glucose metabolized in the brain?
glucose is the primary source of fuel
it is completely oxidized to provide 99% of cerebral energy production
This process is dependant on a number of inportant enzymes and reactions.
How is glucose transported across the blood-brain barrier?
by glucose transporter (GLUT) proteins
How is glucose metabolized, once it is inside the cell membrains?
by glycolosisit is conveted pyruvate.
pyruvate is oxidized into acetyl-coenzyme A, then transported to the mirochondria for entry to the citric acir cycle.
The end product is CO2, water, and energy to produce ATP
How does the neonatal brain make energy during hypoglycemia?
by converting other substrates such as (keyton bodies, lactate, glycerol, and amino acis) into pyruvate.
What 2 hormones regulate glucose levels?
Insulin and Glucogon
How does insulin help regulate glucose?
it is produced by the pancreatic Beta-cells in response to an increase in plasma glucose.
Insulin decreases the blood glucose levels by promoting glycogen formation, supressing the hepatic glucose release, and driving peripheral uptake of glucose.
Insulin
How does Glucogon help to regulate glucose levels?
Is considered a counterregullatory hormone
secreted by panctratic alhpa-cells when blood levels decrease.
promotes glyconeogensis
What are the counterregullatory hormones besides glucogon?
catecholamines, cortisol ang growth hormones
not important in the "fats-feed" cycle they are needed to maitain healthy glucose levels.
Fetal glucose homeostasis
fetal concentrations are 60%-80% of the mother
Glycogen storage begins in early gestation, with most storage in the third trimester
capable of gluconeogensis if needed
What are some early events in neonatal glucose homeostasis?
After clamping the glucose levels fall to it's nadir at 1-2 hours of age
in the first hours the neonates brain metabolizes lactate, which is abundant. even though glucose levels are low the brain has fuel.
The neonate gradually metabolizes glucose to meet
Definition of hypoglycemia
Plasma concentration of 40mg/dl
no single value divides "normal" from "low"
stastistical norms provide a starting point in defining hypoglycemia but the critical threshold need to be individulized.
Incidence of hypopglycemia
1-5 per 1000
30 % of at risk infants
8% in LGA
15% in preterm infant and SGA
Hypoglycemia is usually the result of inadequate hepatic glucose production that cannot keep up with demand or an overproduction of insulin
Psysiologic vs. Pathologic hypoglycemia
the immediate post-natal drop is physiologis
failure to increase blood glucose after 4 hours is pathologic
The brain and hypoglycemia
glucose delivery is dependant on concentration and blood flow.
The brain will increase blood flow during hypoglycemia. placing the infant at risk of brain injury.
The brain will use alternate fuels derived from brain structural components such as protein
Lactic acid and hypoglycemia
becomes elevated in late fetal and early postnatal life.
healthy term infants can produce ketones effectively on day 2-3 thus protect their brains from fuel defiency.
The ability for SGA and preterm infants to effectively mount a counterregulatory respons
Effects or prolonged hypoglycemia
induces biochemical changes at the cell level
accumulitation of glutamate leads to prolonged depomerization with entry of water and Ca+ into the cell
impares neuronal growth
eventually causes cell death
Two categories of hypoglycemia
dininished or inadequate production or substrate delivery
excess utilization or hyperinsulinism
Hypoglycemia
Conditions of inadequate supply/production
prematurity
IUGR
delayed feedings or insufficient breast feeding or fluid re
Errors of metabolism
Glycogen storage disease
Et al.
Hypoglycemia and prematurity
inadequate supply/production
diminished oral or parenteral intake
immature counterregulatory response
insufficient glycogen sotres and release
Hypoglycemia and IUGR
inadequate supply/production
inadequate glycogen and fat stores, increased substrate utilization
Hypoglycemia and errors in metabolism
inadequate supply/production
defective gluconeogensis
Hypoglycemia and gylcogen storage disease
inadequate supply/production
autosomal recessive defects characterized by a deficient or abnormal functioning enzyme involved with the formation or breakdown of glycogen in the liver.
Causes of Hypoglycemia et al.
inadequate supply/production
Perinatal stres/hypoxia
RDS
hypothermia
polycythemia/hyperviscosity
infection
adreal hemmorhage
CHF
Hypoglycemia
Conditions related to hyperinsulinism
IDM
persistant neonatal hyperinsulinism and nesidioblastosis
Beckwith-Wiedemann syndrome
Rh incompatibility
High glufose infusion and tocilytics used before delivery.
terbutaline
UAC placement
Hypoglycemia
Conditions related to hyperinsulinism
persistant neonatal hyperinsulinism and nesidioblastosis
autosomal recessive disorder thought to be caused by regulatory defects in beta-cell function.
Surgical exploration may be necessary for definitive diagnosis with subtotal pancreatectomy the required threapeutic measure.
Hypoglycemia
Conditions related to hyperinsulinism
Beckwith-Wiedemann syndrome
of unknown cause
characterized by omphalocele, marcogolssia, visceromegaly, and hypoglycemia. also abdominal wall defect and ear pit.
Pancreatic islet cell hyperplasia noted
the resultant hypoglycemia may be quite profound and difficult to treat.
visceromegaly
Visceromegaly is enlargement of the internal organs in the abdomen, such as liver, spleen, stomach, kidneys, or pancreas.
marcogolssia
meaning large tongue
Hypoglycemia
Conditions related to hyperinsulinism
Rh incompatibility
severe cases can have beta-cell hypertorphy and hyperinsulinemia
Hypoglycemia
Conditions related to hyperinsulinism
Terbutaline
can stimulate fetal pancreatic beta cells
Hypoglycemia
Conditions related to hyperinsulinism
UAC placement
posistion of the catheter tip near the pancrease may cause glucose to be delivered directly to the pancrease via the celiac artery, resulting in excessive insulin secretion
Clinical presentation of hypoglycemia
Tremors
Jitteriness
irritability
exaggerated moro reflex
high-pitched cry
RDS
stupor, lethergy, hypotonia, refusal to feed
seizures
Whipple's triad
For signs and symptoms to be attributed to hypoglycemia these conditions must be met.
1. a reliable low blood sugar
2. S/S consistant with hypoglycemia must be present
3.S/S must resolve after blood glucose levels return to normal
Presentation of Hypoglycemia and Hypopitutarism
microphallus-small penis see (http://emedicine.medscape.com/article/923178-overview)
midline facial defect
Point of care glucose screening
test strips
used for speed and convience
use whole blood rather than plasma levels
use a enzymatic reagent strip and color chart
may be inaccurate because: whole blood gives a reading 10%-15% lower than plasma, may fail to detect due to unpredicitable measurment, err
Diagnostic studies for hyperinsulinism
include concurrent glucose and insulin levels (insluin will be inappropiately elevated)
ketone and free fatt acid levels (will be low because release of these fuels is supressed)
cortisol
growth hormone levels
Four pronciples gorvening the management of hyppoglycemia
high-risk infants need to be monitored
conformation that PLASMA levels are low
manifestations resolve when glucose level become normal
events are carefully observer and documented
Preventing of hypoglycemia
early feedings. feedingd are preferred. milk provides more energy than the equlilvant volume of IV fluids and may provide more essential nonglucose substrate.
IV glucose at 4-6 mg/kg/min if oral feedings alone are not sufficient to maintain levels
Assessment of glucose status
perform glucose measurements before the first 3-4 feedings or at 2,4,6, 12, 24 and 48 hours if infant is not being fed.
clinically unstable infants
early and exclusive breast-feeding will meet the nutritional and energy requirements of healthy term infant
What if hypoglycemia persists despite feeding?
Correction with IV glucose infusion is necessary.
give a minibolus D10W 2ml/kg IV
followed by a continous infusion of 6-8 mg/kg/min should rapidly increase blood glucose levels but does not address the underlying cause.
Close monitoring of glucose levels
Treatment for ture hyperinsulinism
High IV glucose infusion rates (12-16 mg/kg/min)
delivery of concentrated glucose (greater than 12.5%) requires a centural line to adlminister
Hormonal therapy
corticosteriods
sub-total or total pancreatectomy may be required
What % dextrose requires a centural line to administer?
12.5%
Complications of hypoglycemia
hypoglycemia wil reoccur if a bolus is not followed by a continous inusion
Extravasation may cause tissue necrosis
reactive hypoglycemia may occur if fluids are stopped quickly or infiltration occur.
Outcomes of infants with hypoglycemia
neurologic imparement is associated with hypoglycemia. motor and intelectual deficits
recurrent episodes are strongly correlated with persistant neurodevelopment and physical growth defects.
seizure associated have the worst outcomes
persistant hyperinsul
Pathopysiolog of the IDM
Early in gestation it is associated with higher incidence of malformations.
Third trimester-see 3rd trimester card
after birth- the infants panrease continues to produce excess insulin and glucose is rapidly used
The IDM is at risk because even with plent
IDU in the third trimester
the diabetic mother is increasingly insulin resistant
often has hyperglycemia and hyperaminoacidemia
excess glucose and amino acisd are freely passed across the placenta; insulin is not.
these nurtients stimulate the fetus excess insulin to use the fuels.
Clinical presentation of the IDM
Hypoglycemia
may occur immediately after birth without S/S
the majority will respond to treatment
10% will have persistant hypoglycemia
Clinical presentation of the IDM
Macrosomia/LGA
occurs 35% of the time
some will be SGA because of placental insufficiency in advanced stages
Clinical presentation of the IDM
preterm births
is associated with IDM
Hyperbilirubinemia may be secondary to IDM
Clinical presentation of the IDM
RDS/TTN
hyperinslinemia may retard the maturiation in the pulmonary surfactant system and delay lung maturation
Clinical presentation of the IDM
polycythemia
Hct >65%
insulin induces high glucose uptake and high metabolic rate causes cellular hypoxia. this stimulates over production of RBC's
These polycythemic infant will not always be plethoric
Clinical presentation of the IDM
hypocalcemia/hypomagnesima
result from functional hypoparathyroisism due to maternal magnesium loss
Clinical presentation of the IDM
cardiomyopathy
related to maternal diabetes control and hyper insulinemia
Clinical presentation of the IDM
congenital malformations
Cardiac defects (especially transposistion)
neural tube defects,
sacral agenesis an caudal defects risks are increased
Diagnostic studies for IDM
blood screening with lab conformation of PLASMA glucose
Ca+, Mg, and Hct
X-ray for birth injury
ECG
Complication of the IDM
Seizures
Shoulder dystocia
Renal veign thrombosis secondary to polycythemia
development of juvenile insulin depentant diabetes in 2% females and 6% males
Outcomes of the IDM
increased perinatal mortality due to congeniatl malformations, still birth,and prematurity
neurologic symptoms, developmental delay, behavorial differences, obesity, and diabetes
maternal diabetic control is related to outcomes
SGA outcomes are worse the
Hyperglycemia in neonates
whole blood glucose levels greater than 120-125 mg/dl
PLASMA glucose >150mg/dl
urinary glucose
Incidence of hyperglycemia in noenates
29%-86% in low birth weight
80% <750 gm
45% <1000 gm
2% if >2000 gm
Patho of hyperglycemia
not fully understood in the ELBW infant
normally an increase in glucose stimulates an increase in insulin production thus supressing hepatic production of glucose.
clinically stable ELBW infants can regulate glucose in this way.
Many of them can't. hepati
Hyperglycemia and corticosteriods
stimulates glycogenolosis and gluconeogenesis and may blocksecretion of insulin and inhibit its peripheral action
Etiology of hyperglycemia
low birth weight, extreme prematurity, and IUGR
Excessive glucose load. >6-8 mg/kg.min with 50% receiving 11mg/kg/mg and all 14mg/kg/min
Stress related to clinical problems such as sepsis or infection
diabetes
Dexamethasone therapy for chronic lung diseas
Clinical presentation of Hyperglycemia
onset can be as early as 24 hours; usually before 3 days of life
dehydration, wieght loss, failure to thrive, fever, glycoseuria, ketosis and metabolic acidosis may be seen
Management for hyperglycemia
monitor blood sugar in those at risk. particullarily when fliud intake is increased on day 2-3
decrease glucose load to allow blood glucose level to stabilize at <125mg/dl or plasma <150mg/dl
monitor wieght, urine output, fluid intake, GIR, electrolytes,
Insulin therapy in hyperglycemia
used to attempt to normalize glucose levels without increasing caloric intake
use to treat transient neonatal diabetes
insulin supresses hepatic glucose productiona and increasing glucose utilization
preterm infants have a very small mass of insulin depen
Transient or Permanent Neonatal Diabetes
occurs 1:500,000
predominately in SGA with 46% in the neonatal peroid
23% in childhood or adolescence
31% resolved in the neonatal peroid
75% in the first 10 days of life
family history
Etiology of Transient or Permanent Neonatal Diabetes
prematurity
ELBW
SGA
IUGR
Clinical presentation of Transient or Permanent Neonatal Diabetes
Hyperglycemia >600mg/dl
polyuria, glycosuria, weight loss, dehydration, fever, fialure to thrive, ketosis and metabolic acidosis. LOW levels of C-peptide and plasma insulin
TRANSIENT: last for several weeks or months. indicated by rise in C-peptide
Management of Transient or Permanent Neonatal Diabetes
restore volume
replace fluids and electrolytes
correct glucose levels and monitor
provide nutrition
individualize dose of insulin 0.2-3 units/kg/day usual dose to keep plasma 100-180 mg/dl for 2 weeks to 18 months
Outcomes in Transient or Permanent Neonatal Diabetes
normal developmental milestones when properly treated with insulin.