acidosis and ketosis
TRANSCRIPT
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