Download MBBS Biochemistry PPT 37 Biochemistry Of Starvation Lecture Notes

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Induction To Todays Topic

Can Any One Guess

Todays Topic Of Teaching and

Learning?
Biochemistry Of

Starvation

Specific Learning Objectives

? What is Starvation?
? Which Conditions develop Starvation?
? What are Stages/Phases of Starvation?
? Which Hormones play imp role in starvation?
? Factors of Biochemical adaptation in Starvation
? How Organs adapt to Starvation?
? What are Consequences of Starvation?
What Is Starvation?

?Starvation is

complete stoppage

of eating food by a

human body.

What Is Total Starvation?

?Total starvation is

complete stoppage

of Food and Water.
Conditions Developing Starvation

Conditions Developing Starvation

? Food Scarcity
(Natural Calamities , Draughts Floods and ,Famines)
? Extreme Poverty
? Lost in Sea routes for long durations
? Clinical Conditions: Major Surgeries, Severe Burns
? Desire to loose rapid weight
? Political Issues: Hunger Strikes
During

Starvation

Body

is under

Metabolic Stress

Features Of Starved Body

? No entry of exogenous food nutrients

? Starved body is deprived of:

?Calories (Carbs and Lipids)

?Building blocks (Proteins)

?Growth Factors(Vitamins and Minerals)

?Protectors (Antioxidants)
Biochemical Adaptations

During Starvation

Important Factors Responsible For

Adaptation In Starvation

? Content Of Endogenous Stores
? Health of Associated Organs and System
? Associated Metabolic Processes involved with:

?Hormones
?Enzymes
?Coenzymes
? During Starvation a body is in an

emergency/critical condition

? Has to face Biochemical Chal enge
? Has to get adapted
? Manage with endogenous metabolite

reserve stores

? Communicate and Cooperate through

hormones

?Overcome state by biochemical alterations
?Try Survive as per condition

Survival Period During Starvation
? Survival period during Starvation

depends upon :

? Reserve TAG stores of Adiposecytes:

?More content of TAG in Adiposecytes

?More is duration of survival in

Starvation and vice a versa.

Length Of Survival In Starvation

? Due to deprivation of only Food:

?3 to 4 Weeks

?Longer up to 65 days

? Deprivation of water alone then

survival is only for few days

?Less than a week
Effects Of Starvation

OR

Human Body Adaptation In

Starvation



Biochemical Alterations In

Starvation

Different Modes

To Study Biochemical

Adaptations

During Starvation Phases
Study Of Biochemistry Of Starvation

With Respect To

?Stages
?Metabolism
?Organs

Alternative Adaptations

In Different

Metabolic Processes

During Starvation
Occurrence Of

Four Stages During Starvation

OR

Metabolic Alterations During

Starvation

Starvation

Metabolic Alterations

Stages

1

Increased Glycogenolysis

2

Proteolysis

Glucose Alanine Cycle

Increased Gluconeogenesis

3

Increased Lipolysis

Fatty acid Beta Oxidation(Incomplete)

4

Increased Ketogenesis

Ketosis




Fasting ? Early Stage

Muscle

Alanine / Pyruvate

Brain

Glucose

Glutamine

Glycerol

Gluconeogenesis

Fat

Ketogenesis

Ketones

AGL

Liver

Ureagenesis

Ketones

Urea

NH3

Kidney

Intestine


Fasting ? Late Stage

Muscle

Alanine / Pyruvate

Brain

Glucose

Glutamine

Glycerol

Gluconeogenesis

Fat

Ketogenesis

Ketones

AGL

Liver

Ureagenesis

Ketones

Urea

NH3

Kidney

Intestine

Role Of Hormones In Starvation
? When food is in Short supply
? Metabolic activity decreases

to spare fuel.

? Conservation of energy is

basic adaptive response to

calorie reduction

? Hormones influences an

utilization of endogenous

reserve stores and

? Supply fuels to body

organs during starvation

phase.


Hormonal Alterations In Starvation

? Insulin secretion

decreased

? Glucagon and Epinephrine

increased

Metabolic Role Of Hormones
Hormonal Influences In Starvation

H ormone

Source

Change in

Secretion

Norepinephrine Sympathetic



Nervous System



Norepinephrine Adrenal Gland

Epinephrine

Adrenal Gland


Thyroid

Thyroid Gland



Hormone T4

(changes to T3

peripherally)

?Norepinephrine and T3

participate to


?Decrease metabolic

activity when calorie

intake decreases.
? Thus biochemical alterations during

Starvation are influenced by hormonal

actions.

? Glucagon and Epinephrine in starvation

act upon target organs

? Stimulate metabolic pathways which

supply fuels

? Improve survival phase during

Starvation.

Metabolic Alterations In Starvation
Biochemical Alterations Of

Carbohydrate Metabolism

During Starvation Phase

Carbohydrate Metabolism

In Liver During Starvation Phase

? Glycogenolysis Increased

? Glycogenesis Decreased

? Glucose Alanine Cycle increased

? Gluconeogenesis Increased

? Glycolysis Decreased

? TCA operation Decreased

? HMP Shunt Decreased

? Blood Glucose level Decreases (later stages)

? Cellular Glucose Deprivation (In Muscle Cells)


?PDH a Multi Enzyme

Complex is inhibited

during Starvation
Alterations In Protein Metabolism

During Starvation

Proteins Serve as Calorific

During Starvation

? Muscle Proteins are catabolized to provide

carbon skeleton for Liver Gluconeogenesis

? Liver Gluconeogenesis increased via Glucose

Alanine cycle regulates blood Glucose levels

? Glucose produced initially via Gluconeogenesis

to Brain and Erythrocytes
Protein Metabolism During Starvation

? As Glucose levels lowers in blood

? Catabolism Of Muscle Proteins

increased

? Transdeamination reaction of

Amino acids is increased

? To release Glucogenic amino acids

? Glucose Alanine Cycle elevates

? Ammonia Detoxification and

Urea production increased

initial y and decreased as

Starvation phase prolongs.

? Body is in negative Nitrogen

Balance.

? Concentration of Functional

Proteins Decreases.


Nitrogen Excretion in Starvation

12



a
y
)

n
(
g
/d

8

Normal Range

x
c
r
e
t
io

4

Partial Starvation

N
it
r
o
g
e
n
E

Total Starvation

0

10

20

30

40

Days

Long CL et al. JPEN 1979;3:452-456

Glucose Nitrogen Ratio

Increased In Starvation


Biochemical Alterations of

Lipid Metabolism In Starvation


Lipid Metabolism During Starvation

? Lipolysis is Increased
? Mobilization of Free Fatty acids increased
? Beta oxidation of Fatty acids increased
? Incomplete Fatty acid Oxidation increased
? Ketogenesis Increased
? Ketolysis Decreased
? Ketosis Noted (Ketoacidosis)-Rotheras Test +ve
? Lipogenesis is Decreased
?Enzyme Acetyl Carboxylase

is inhibited during

Starvation

Levels Of Ketone Bodies

Increases

As

Starvation Phase Prolongs


Increased Ketogenesis In Starvation

What Happens? When Ketone body production

Exceeds than the Ketone body Utilization?

? When Prolonged Starvation ?

? Cellular Glucose deprivations occurs
? Glycogen stores depletes within 24 hrs of fasting
? Fat burns under flame of Carbohydrates
? Fatty acid are incompletely oxidized
? Acetyl-CoA of fatty acid oxidation is metabolized to

ketone bodies and mobilized out of Hepatocytes

? Ketogenesis increased Ketolysis decreased
? Leads to Ketosis-Ketonemia and Ketonuria
Prolonged Starvation Leads to

? Ketosis (Ketonemia and Ketonuria)

? High levels of Ketone Bodies in blood and

urine

? Ketoacidosis

? Severe Ketosis
? Lowered blood pH
? Nausea ,Acetone breath
? Coma, Death

?3 days starvation

[Ketone Bodies]=3mM

?3 weeks starvation

[Ketone Bodies]=7mM


Cure For Ketosis

? Ketosis Cured by infusion of

Glucose.
During Starvation

Alterations Occur In

Water and Electrolyte

And

Acid Base Balance

? Reduction in Body Water
? Reduction of Potassium ions
? Acidic blood pH due to

increased Ketone bodies
?On prolonged phase of

Starvation there results

?Severe dehydration and

Acid Base imbalance

Starvation Alters BMR

? BMR is first affected in starvation

? In starvation metabolism decreases

? During starvation BMR is Decreased


Biochemical Adaptations

By Organs

During Starvation Phase







The Fasting State:

Glucagon stimulates glucose

production and release in liver.

Also mobilizes the fatty acids

(sparing Glucose for the Brain)












FUEL CHOICE DURING STARVATION

1. Insulin

6. Ketone bodies

5. Fatty acids

2.Glucagon

nge

3 .Glucose

l
a
t
i
v
e

cha

Re

4. Glycogen

24

Hours of Starvation

Changes Of Liver Glycogen Content
During Starvation

? Fuel changes from Glucose to Fatty acids to

Ketone bodies

Metabolic Response To Fasting







Metabolic Response to Starvation is

Characterized

? Switch from carbohydrate metabolism to fat

metabolism,

? Context of a hypometabolic state, with minimized

catabolism

? Initial y, stores of carbohydrate precursors (eg.

glycogen) are depleted via Glycogenolysis within 24 hrs.

? In first 24-48 hours there is increased gluconeogenesis

from amino acids and glycerol.


? Subsequently, Ketogenesis takes over, and much of the

body metabolic needs are met by ketone bodies and

free fatty acids.

? This is the consequence of decreasing insulin levels,

and relatively increased influence from catecholamines

and cortisol.

? Over prolonged starvation, protein catabolism begins,

resulting in degradation of structural y important

proteins, and organ system dysfunction.


Differentiation In

Well Fed And Fasting States

Of Human Body
WELL-FED STATE

FASTING STATE

Hormones

Insulin

Glucagon,

Adrenaline, Cortisol

Hyperglycemia

Hypoglycemia

Response of

Glycogenesis

Lipolysis

the body

Lipogenesis

Ketogenesis

Protein synthesis

Proteolysis

WELL-FED STATE

FASTING STATE

Source of

from stores

(Glycogen)

Glucose

from food

Gluconeogenesis

Fate of

Glycolysis

Glucose

formation of Glycogen and

Glycolysis

TAG stores
WELL-FED STATE

FASTING STATE

Source of

from food TAG

from storage TAG

Fatty acids

-oxidation

Fate of Fatty

-oxidation

(Incomplete one)

acids

synthesis of TAG and

Store as Depot Fat

Ketogenesis

WELL-FED STATE

FASTING STATE

Source of

Amino acids

from food

From muscle Proteins

Glucogenic amino

Fate of

Protein synthesis

acids

Amino acids

Produce Glucose via

Gluconeogenesis


Preferred fuels By Human body

In the Well-Fed and Fasting States

Organs

Well-Fed

Fasting

Liver

Glucose & Fatty

Fatty acids

acids

Resting skeletal

Glucose &

Fatty acids & KB

Muscle

Fatty acids

Cardiac muscle

Fatty acids

FA,AA & KB

Adipose tissue

Glucose

Fatty acids

Brain

Glucose

Glucose ,Later KB

RBCs

Glucose

Glucose
BIOCHEMICAL PROFILE OF EARLY FASTING STATE

Blood Glucose levels decreases

65 mg/dl

Active Glycogenolysis

Muscle and Liver

Shift of metabolic fuel from Glucose to fatty

acidsFatty acid mobilization from adipose tissues

Gluconeogenesis

Glucose Alanine cycle

BIOCHEMICAL PROFILE OF STARVED STATE

GLUCOSE levels more decreased

40 mg/dL

PROTEIN CATABOLISM increased

Sequesters Nitrogen as urea
Excretes 20 to 30 grams daily

Gluconeogenesis taking place using precursors as

Amino acids
Lactate
Glycerol

KETONE BODIES increased

Acetyl CoA converted to ketone bodies via Ketogenesis
In Prolonged Starvation

? After 3 days of Starvation -> Liver

forms large amounts of Ketone

bodies

( Due to shortage of Oxaloacetate)
? Ketone Bodies -> released into blood
? Brain and Heart start to use ketone

bodies as fuel during phase of

Starvation.

Starvation Of Several Weeks

? After several weeks of starvation ->

Ketone bodies become major fuel of

Brain

? After depletion of TAG stores
? Proteins degradation accelerates
? Death due to loss of Heart, Liver,

and Kidney function.


Consequences Of Starvation
? Severe Nutrient deficiency
? Affects vitality and Damages Important

Internal Organs /System

? Anaemia (Iron and Protein deficiency)
? Decreased BMR
? Fatigue, Weakness
? Low Immunity
? Increases Sleep

? Night blindness (Vitamin A deficiency)
? Scurvy (Vitamin C deficiency)
? Irregular Menses
? Constipation
? Bone Loss
? Dehydration


? Water Electrolyte Imbalance
? High Blood Pressure
? Brain Defects
? Coma and Death (Life Ends)
Questions

? Explain the different stages of

starvation & biochemical alterations

in the body during these stages.

OR

? Biochemical alterations/adaptations

during starvation.
? Describe role of following

organs during various stages of

starvation

? Liver
? Brain
? Muscles
? Adipose tissues

THANK YOU

Biochemistry

This post was last modified on 05 April 2022