3.1 - Glucose Homeostatis Flashcards

1
Q

Exam ?

Fetal glucose homeostasis

A
  • During the third trimester the fetus prepares for the extra uterine survival by increasing energy stores
  • developing metabolic process for rapid glucose production and utilizatoin
  • Key metabolic processes which influence glucose homeostasis are:
    • Glycolysis
    • Gluconeogenesis
    • Glycopenolysis
  • to maintain homeostasis depends on the adequate supply of glycogen and fat and on mature or intact hormonal regulatory mechanisms
  • Insulin and glucagon are the important hormones for regulating glucose levels
  • From 12 weeks gestation the fetus can synthesise these hormones however has a limited ability to secrete them from the pancreas. Even when challenged with a glucose load
  • Insulin inhibits gluconeogenic enzyme induction and suppresses glucose production in the liver
  • Insulin plays an important part in the fetal growth because it stimulates grow of the:
    • Cardiac muscle
    • Adipose tissue
    • hepatic tissue
    • cognitive tissue
    • skeletal tissue
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2
Q

Exam ?

Neonate at risk of hypoglycaemia

A
  • maternal diabetes
    • gestational
    • Type 1
    • Type 2
  • Small for gestational age
  • Growth restricted
  • preterm babies with low birth weight
  • babies born under significant stress
  • maternal treated with certain medications ie Terbutaline
  • Large for gestation age - macrosomia
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3
Q

Exam ?

Symptoms of hypoglycaemia in the neonate

A
  • shakiness/jitterness
  • blue tint to skin and lips (cyanosis)
  • Apnea
  • Low body temp ( hypothermia)
  • poor muscle tone
  • not interested in feeding
  • lack of movement and energy (lethargy)
  • Seizures
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4
Q

Exam ?

Identify risk factors for the mother and her fetus/neonate related to poor glycaemic control during pregnancy

A

If poor qlycaemic control during pregnancy

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5
Q

Hypoglycaemia due to inadequate substrate supply high be excepted in

A
  • the premature infant
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6
Q

the most common reason for neonatal hypoglycemia is

A
  • Hyperinsulinaemia
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7
Q

Glycolysis

A
  • Glycolysis is the process in which glucose is broken down to produce energy. It produces two molecules of pyruvate, ATP, NADH and water. The process takes place in the cytoplasm of a cell and does not require oxygen.
  • Is the first step in the breakdown of glucose to extract energy for cellular metabolism.
  • Glycolysis consists of an energy-requiring phase followed by an energy-releasing phase.
  • there are 10 steps
  • Step 1. A phosphate group is transferred from ATPATP, A, T, P, end text to glucose, making glucose-6-phosphate. Glucose-6-phosphate is more reactive than glucose, and the addition of the phosphate also traps glucose inside the cell since glucose with a phosphate can’t readily cross the membrane.
  • Step 2. Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate.
  • Step 3. A phosphate group is transferred from ATPATP A, T, P, end text to fructose-6-phosphate, producing fructose-1,6-bisphosphate. This step is catalyzed by the enzyme phosphofructokinase, which can be regulated to speed up or slow down the glycolysis pathway.
  • Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate (DHAPDHAPstart text, D, H, A, P, end text) and glyceraldehyde-3-phosphate. They are isomers of each other, but only one—glyceraldehyde-3-phosphate—can directly continue through the next steps of glycolysis.
  • Step 5. DHAPDHAPstart text, D, H, A, P, end text is converted into glyceraldehyde-3-phosphate. The two molecules exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the scheme of the diagram above, as glyceraldehyde-3-phosphate is used up. Thus, all of the DHAPDHAPstart text, D, H, A, P, end text is eventually converted.
  • Step 6. Two half reactions occur simultaneously: 1) Glyceraldehyde-3-phosphate (one of the three-carbon sugars formed in the initial phase) is oxidized, and 2) NAD+NAD+start text, N, A, D, end text, start superscript, plus, end superscript is reduced to NADHNADHstart text, N, A, D, H, end text and H+H+start text, H, end text, start superscript, plus, end superscript. The overall reaction is exergonic, releasing energy that is then used to phosphorylate the molecule, forming 1,3-bisphosphoglycerate.
  • Step 7. 1,3-bisphosphoglycerate donates one of its phosphate groups to ADPADPstart text, A, D, P, end text, making a molecule of ATPATP, A, T, P, and turning into 3-phosphoglycerate in the process.
  • Step 8. 3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate.
  • Step 9. 2-phosphoglycerate loses a molecule of water, becoming phosphoenolpyruvate (PEPPEP, P, E, P,). PEPPEPP, E, P, is an unstable molecule, poised to lose its phosphate group in the final step of glycolysis.
  • Step 10. PEPPEP P, E, P, readily donates its phosphate group to ADPADPstart text, A, D, P, end text, making a second molecule of ATPATP, A, T, P, \t. As it loses its phosphate, PEPPEPP, E, P, is converted to pyruvate, the end product of glycolysis.
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8
Q

Gluconeogensis

A
  • glucose level 60 -150 mg/dl
  • Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates.
  • It is a ubiquitous process, present in:
    • plants,
    • animals,
    • fungi,
    • bacteria,
    • other microorganisms.
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9
Q

the creation of glucose from noncarbohydrate sources is called

A
  • Gluconeogensis
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10
Q

Glucogenolysis

A
  • It means the body cannot process certain amino acids (the “building blocks” of protein), causing a harmful build-up of substances in the blood and urine.
  • Glycogenolysis is the biochemical pathway in which glycogen breaks down into glucose-1-phosphate and glucose.
  • The reaction takes place in the hepatocytes and the myocytes.
  • The process is under the regulation of two key enzymes:
    • phosphorylase kinase
    • glycogen phosphorylase.
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11
Q

exam ?

Glycogen

A

Glycogen is the stored form of glucose that’s made up of many connected glucose molecules. Glucose (sugar) is your body’s main source of energy. It comes from carbohydrates (a macronutrient) in certain foods and fluids you consume

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12
Q

Explain why glucose utilisation is increased during cold stress (you might need to review week 1 notes to make this link)

A
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13
Q

Causes of hypoglycemia in newborn baby

A
  • Poor nutrition of the mother through pregnancy
  • Poorly controlled maternal diabetes (fetus making too much insulin)
  • incompatible blood type of mother and baby (severe haemolytic disease of the newborn)
  • increase insulin in baby’s stool ? tumour of the pancreas
  • birth defeats
  • cognenital metabolic disease or hormone deficiencies
  • birth asphyxia
  • liver disease
  • infection
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14
Q

Why are newborn brains so prone to the effects of hypoglycemia?

A

1: They are growing a lot during this time

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15
Q

Fetal glycogen storage

A

Much of fetal glycogen storage occurs during the last 30% of gestation, and is promoted by a high insulin:glucagon ratio as well as high cortisol.

If the infant experiences hypoglycemia or hypoxemia during this period, glycogen phosphorylase will be activated to defend the fetal energy supply, however this means that after birth the infant will have less glycogen stored to maintain its blood sugar.

This also means that premature infants have less stored glycogen and are thus at greater risk for hypoglycemia.

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16
Q

The average healthy infant has a ___ supply of glycogen at birth

A

The average healthy infant has a 10 hour supply of glycogen at birth

Consequentially, babies need to start feeding soon after birth.

17
Q

Paradoxically, both ___ infants and ___ infants are at risk for hypoglycemia

A

Paradoxically, both IUGR infants and LGA infants are at risk for hypoglycemia

18
Q

Etiologies of transient neonatal hypoglycemia

A
  • Prematurity
  • IUGR
  • Asphyxia
  • Hypothermia
  • Sepsis
  • Maternal diabetes (CDM or GDM)
  • Erythroblastosis fetalis
  • Exposure to beta-agonist tocolytics
19
Q

Etiologies of neonatal hypoglycemia with prolonged periods of hypoglycemia

A

Familial hyperinsulinism

Inborn errors of metabolism (glycogen storage diseases)

20
Q

Most common cause of hyperinsulinism of the newborn

A

Maternal diabetes

21
Q

Mechanism of hyperinsulinism in erythroblastosis fetalis

A

Infants with erythroblastosis fetalis have an increased number of pancreatic beta cells, which thereby causes hyperinsulinism.

The reason for this is not fully understood.

22
Q

Familial recessive hyperinsulinism

A
  • Defect in the K+-ATP channel in beta cells
  • Causes congenital, persistent hyperinsulinism
23
Q

___ should be strongly suspected in the term infant who has hypoglycemia without apparent risk factors.

A

Sepsis should be strongly suspected in the term infant who has hypoglycemia without apparent risk factors.

24
Q

Confirming a diagnosis of hyperinsulinemia in the newborn

A
  • Two ways:
    1. Demonstrate elevated insulin when the infant is hypoglycemic with symptoms
    2. Demonstrate elevation in IGFBP-1 (insulin-like growth factor binding protein-1)
25
Q

Management of asymptomatic hypoglycemia

A

In infants with hypoglycemia who display no symptoms, enteral feeding with formula may be attempted first.

Formula is better than dextrose in water as its protein and fat will create a sustained elevation in blood sugar, while dextrose will provide only a temporary boost.

Even if concentrations normalize, continue monitoring preprandial and postprandial glucose levels.

26
Q

Adjunct pharmacologic therapies for refractory neonatal hypoglycemia

A
  • Hydrocortisone or Prednisone: Decrease peripheral glucose utilization
  • Glucagon: Stimulates glycogenolysis
  • Diazoxide: Inhibits insulin secretion
  • Octreotide acetate (somatostatin acetate): Inhibits insulin and GH release
27
Q

Hypoglycemia brain injury

A

Even as blood sugar varies, CSF sugar remains fairly constant as it is regulated by glucose transporters at the choroid plexus, not just simple diffusion. Infants with moderate hypoglycemia are therefore more at risk of intraventricular hemorrhage due to changes in bloodflow secondary to hypoglycemia rather than neuroglycopenia.

If blood sugar is very low and does result in neuroglycopenia, glutamate builds up in the synaptic clefts and binds to NDMA-receptors (predominant glutamate receptors in the neonatal brain), resulting in excitotoxicity that manifests as seizure and areas of brain necrosis.

28
Q

Hypoglycemia brain injury

A

Even as blood sugar varies, CSF sugar remains fairly constant as it is regulated by glucose transporters at the choroid plexus, not just simple diffusion. Infants with moderate hypoglycemia are therefore more at risk of intraventricular hemorrhage due to changes in bloodflow secondary to hypoglycemia rather than neuroglycopenia.

If blood sugar is very low and does result in neuroglycopenia, glutamate builds up in the synaptic clefts and binds to NDMA-receptors (predominant glutamate receptors in the neonatal brain), resulting in excitotoxicity that manifests as seizure and areas of brain necrosis.

29
Q
A