Metabolism and Metabolomics

BSBT 513

Acidosis and KetosisPresented by

Sakshi SaxenaIBT VIth sem

ASU2013010200124

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O2

Distributed to tissues all over the body

O2 in tissues

What’s next?Glucose

PyruvateAcetyl

CoATCA

O2 in tissues Glucose

PyruvateAcetyl

CoATCA

Lactic Acid

Low pH

What’s next?

Buffered with bicarbonate ions (HCO3

- )

Decrease in bicarbonate ions in Blood

Increase in CO2

Compensation

pH HCO3-

ACIDOSIS

Result on blood?

pH HCO3-

ACIDOSIS

Result on blood?

Increase in Anion Gap

Normal Anion Gap

PossibilitiesCauses

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•Sodium bicarbonate (NaHCO3) is the agent most commonly used to correct metabolic acidosis.

•HCO3- deficit = deficit/L (desired serum HCO3

- - measured HCO3-) × 0.5 × body weight

(volume of distribution for HCO3-)

•HCO3- can be administered intravenously to raise the serum HCO3

- level adequately to increase the pH to greater than 7.20.

•Citrate salts are available in a variety of formulations, as mixtures of citric acid with sodium citrate and/or potassium citrate.

•Potassium citrate is useful when the acidosis is accompanied by hypokalemia but should be used cautiously in persons with renal impairment and must be avoided in those with hyperkalemia.

Treatment

KETOSIS

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Available Options1. Glycogen = Strings of Glucose stored in body!

2. New glucose molecules

a. Fats - Fatty acids

b. Proteins - Amino acids

https://www.youtube.com/watch?v=I4lU4zQJQRk

Starvation StateGlucagon Insulin Low glucose levels in

blood

Fatty Acid Oxidation(Occurs In liver)

Fatty Acids Acetyl CoA Kreb’s Cycle

ETCATP

Starvation StateGlucagon Insulin Low glucose levels in

blood

Fatty Acid Oxidation(Occurs In liver)

Fatty Acids Acetyl CoA Kreb’s Cycle

ETCATP1-2 days of fasting!

Starvation State

Fatty Acids Acetyl CoA Kreb’s Cycle

ETCATP

In following days of fasting!

Auto-regulation/inhibition

1. Increased Acetyl CoA 2. Increase in ATP

Starvation State

Fatty Acids Acetyl CoA Kreb’s Cycle

ETCATP

In following days of fasting!3. Increase in ATP will ask ETC to slow down4. This will result in accumulation of NADH5. Resulting in slow Kreb’s cycle6. So, no Acetyl CoA is being used now.

NADH

Starvation StateIn following days of fasting!

Excess Acetyl CoA Ketones (In Liver)

Reach all tissues of theBody including Brain viaBlood Brain barrier.

Ketosis is a metabolic state where the liver produces small organic molecules called ketone bodies.

Ketosis

Is Ketosis good or bad?

• It is a smart strategy to cope up with starvation or fasting.

• It decreases the need of gluconeogenesis and thus saves proteins from being used up during starvation.

• Ketone bodies are better fuels. • 100 g of glucose generates 8.7

kg of ATP, 100 g of 3-hydroxybutyrate can yield 10.5 kg of ATP, and 100 g of acetoacetate 9.4 kg of ATP.

• Accumulation of ketones in blood lowers blood’s pH resulting in metabolic disorder called ketoacidosis.

KETOACIDOSISAlcoholic Diabetic

In alcoholic ketoacidosis, alcohol causes dehydration and blocks the first step of gluconeogenesis by depleting oxaloacetate.

The body is unable to synthesize enough glucose to meet its needs, thus creating an energy crisis resulting in fatty acid metabolism, and ketone body formation.

The lack of insulin in the bloodstream prevents glucose absorption, thereby inhibiting the production of oxaloacetate through reduced levels of pyruvate and can cause unchecked ketone body production.

Hyperglycemia results in glucose overloading the kidneys and spilling into the urine.

Dehydration results following the osmotic movement of water into urine (Osmotic diuresis), exacerbating the acidosis.

KETOACIDOSISSymptoms

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Treatment1. Fluid replacement : either by mouth or through a vein (intravenously) until the

body is well rehydrated. The fluids will replace those that have been lost through excessive urination, as well as help dilute the excess sugar in your blood.

2. Electrolyte replacement.: Electrolytes are minerals in the blood that carry an electric charge, such as sodium, potassium and chloride. The absence of insulin can lower the level of several electrolytes in the blood. Electrolytes will be provided through a vein to help keep the heart, muscles and nerve cells functioning normally.

3. Insulin therapy: Insulin reverses the processes that cause diabetic ketoacidosis. Insulin therapy is done usually through a vein. When the blood sugar level falls below 240 mg/dL (13.3 mmol/L) and the blood is no longer acidic, intravenous insulin therapy is stopped and normal insulin therapy is recommended.

SummaryMetabolic state Cause Symptoms Treatment

Acidosis Shock, sepsis, diarrhea, kidney failure, loss of ionsResulting in low blood pH

Nausea, vomiting, short breath, increased heart rate, sleepiness

Bicarbonate ions administration

Ketosis Acetyl CoA accumulation

Fruity breath, dry mouth, vomiting

Electrolyte replacement

1. METABOLIC EFFECTS OF THE VERY-LOW-CARBOHYDRATE DIETS: MISUNDERSTOOD “VILLAINS” OF HUMAN METABOLISM . Anssi H. Manninen. Journal of the International Society of Sports Nutrition. 1(2):7-11, 2004.

2. “How does body adapt t starvation” : A video by KhanAcademy. Accessed from https://www.youtube.com/watch?v=I4lU4zQJQRk

3. “Acidosis made easy” A series of videos by ftplectures. Accessed from https://www.youtube.com/watch?v=YTwgAVZ3CWM

4. http://www.docsopinion.com/2014/06/02/ketosis/

5. http://emedicine.medscape.com/article/118361-treatment

REFERENCES