619 GLA 8/12 pt 2 Lipid Metabolism

Ketones

made from excess acetyl CoA in the liver, typically occurs in the fasted state when there is a high rate of beta-oxidation happening in the liver

What impacts hormone sensitive lipase?

inhibited by insulin

activated by glucagon, cortisol, and epinephrine

Hormone Sensitive Lipase in Ketonegenesis

key factor, when there is a lot of lipolysis, ketones will increase

2 Key Highlights of Ketone Synthesis

the rate-limiting step is catalyzed by HMG CoA Synthase

the ketones initially produced are acetoacetate and beta-hydroxybutyrate

Rate-Limiting Step of Ketone Synthesis is Catalyzed By

HMG CoA synthase

2 Ketones Initially Prouduced in Ketone Synthesis

acetoacetate (can be converted to acetone and exhaled)

beta-hydroxybutyrate

Ketoacidosis

occurs when ketone production exceeds use

3 Illnesses Ketoacidosis is Commonly Associated With

type 1 diabetes

starvation

excessive alcohol consumption

Ketones Normally

tissues will use ketones synthezised by the liver for energy (convert it back into acetyl CoA and go into TCA cycle)

Hormone Sensitive Lipase in Diabetic Ketoacidosis

since hsl is inhibited by insulin, if there is not sufficient insulin to counterbalance the effects of other hormones, excessive lipolysis will ultimatley lead to ketone over production

What test is used to detect ketones?

as ketone levels increase in the bood they will be filtered by the kidneys and appear in the urine

a urine dipstick test will show only trace amounts of ketones after an overnight test

Problem with Urine Dipstick Tests for Ketone Detection

urine dipstick tests only detect acetoacetate, and not beta-hydroxybutrate

this can lead to a false negative result, particularly in alcohol ketoacidosis where there is upregulation of NADH resulting in more beta-hydroxybutrate in the urine

What is a more accurate way to measure ketones?

direct measurement of beta-hydroxybutyrate in serum

What do most inherited disorders of fatty acid oxidation present with?

fasting hypoglycemia

How do lipid problems cause hypoglycemia?

the liver carries out gluconeogenesis in fasting state to maintain blood glucose levels, and the main source of fuel for the fasted liver is fatty acids

What level should be elevated in a patient with hypoglycemia?

ketones

Why do patients wtih beta-oxidation disorder not have ketones with hypoglycemia?

because ketone synthesis relies on the accumulation of acetyl coa, which occurs when there is a lot of fatty acid oxidiation happening

Atypical Characteristic of Patients with Beta-Oxidation Disorders

the unexpected pairing of hypoglycemia with undetectable or low ketones

4 Causes of Persistent Hypoglycemia in Children/Infants

hormone problem

metabolic problem

malnutrition

liver problem

4 Metabolic Problems that can Cause Persistent Hypoglycemia in Children/Infants

disorders of glycogen synthesis/degradation or glucoeogenesis

disorders of fatty acid metabolism

disorders of amino acid metabolism

galactosemia/aldolase b deficiency

Symptoms of Disorders of Glycogen Synthesis/Degradation or Glyconeogenesis

fasting hypoglycemia (more severe in disorders of gluconeogenesis

mild to moderate ketosis

lactic acidosis common in gluconeogenic disorders

Symptoms of Disorders of Fatty Acid Metabolism

fasting hypoglycemia

inappropriately hypoketotic

VCAD, LCAD, MCAD deficiency

carnitine or CPT deficiency

6 Beta-Oxidation and Glycogen Disorders

primary carnitine deficiency

cpt i deficiency

cpt ii deficiency

mcad or lcad deficiency

glucose-6-phosphatase defeciency

liver glucogen phosphorylase deficiency

Primary Carnitine Deficiency Lab Findings

beta-oxidation disorder, fasting hypoglycemia, low plasma free carnitine, potential dicarboxylic acids

CTP I Deficiency Lab Findings

beta-oxidation disorder, fasting hypoglycemia, high plasma free carnitine, potential dicaboxylic acids

CPT II Deficiency Lab Findings

beta-oxidation disroder, fasting hypoglycemia, high plasma acylcarnitines, potential dicaboxylic acids

MCAD or LCAD Deficiency Lab Findings

beta-oxidation disorder, fasting hypoglycemia, high plasma acyl carnitines, potential dicarboxylic acids

Glucose 6-Phosphate Deficiency Lab Findings

glycogen disorder, fasting hypoglycemia, high ketones, lactic acidosis, hyperuricemia

Liver Glycogen Phosphorylase Deficiency Lab Findings

glycogen disorder, fasting hypoglycemia, high ketones

Other Common Symptoms of Beta-Oxidation Disorders

liver dysfunction, skeletal and/or cardio myopathy due to cellular damage

What can patients with beta-oxidation disorders occuring upstream from MCAD be treated with?

medium chain fatty acids