Chapter 22b

Chapter 22b

Metabolism and Energy Balance

Figure 22-8a

Homeostatic Control of Metabolism

• Endocrine pancreas secretes hormones insulin and glucagon. These control blood sugar.

Figure 22-8b


Homeostatic Control of Metabolism• In the fed state, high levels of plasma glucose and amino

acids result in the secretion of insulin.

• Note effects of insulin √

Figure 22-9a

Figure 22-9b


• In the fasting state, low plasma glucose results in the secretion of glucagon

• Note effects of glucagon √


• Levels of glucose, glucagon, and insulin vary over a typical 24-hour period

Figure 22-10

Factors That Control Insulin Secretion

1 - Increased plasma glucose2 - Increased plasma amino acids3 - Feedforward effects of GI hormones4 - Parasympathetic activity5 - Sympathetic activity

Insulin Promotes Anabolism

• Increases glucose transport into most, but not all, insulin-sensitive cells

• Enhances cellular utilization and storage of glucose

• Enhances utilization of amino acids• Promotes fat synthesis

Figure 22-12a

Glucose Uptake by Adipose Tissue and Resting Skeletal Muscle is Insulin-Sensitive

• In the absence of insulin, glucose cannot enter cell

Figure 22-12b

Insulin Enables Glucose Uptake by Adipose Tissue and Resting Skeletal Muscle

• Insulin signals the cell

Insulin Indirectly Alters Glucose Transport in Hepatocytes

• Hepatocyte in fed state

Figure 22-13a

Figure 22-13b

Insulin Indirectly Alters Glucose Transport in Hepatocytes

• Hepatocyte in fasted state

Fed State: Insulin is an Anabolic Hormone

• Insulin promotes• Glucose uptake• Glucose

metabolism• Energy storage

as glycogen and fat

Figure 22-14

Plasmaglucose

cellsof pancreas

cellsof pancreas

Insulin

GlycolysisGlycogenesisLipogenesis

Muscle, adipose,and other cells

Plasmaglucose

Negativefeedback

Liver

Glucose transport

Stimulus Integrating centerEfferent pathEffectorTissue responseSystemic response

KEY

Glucagon Is Dominant in the Fasted State

• Glucagon is anatgonistic to most actions of insulin, resulting in a catabolic state in the body

Figure 22-9b

Endocrine Response to Hypoglycemia

Figure 22-15

Diabetes Mellitus is a Family of Diseases

• Diabetes mellitus is a condition characterized by chronic elevated plasma glucose levels, or hyperglycemia

• Diabetes is reaching epidemic proportions in the USA

• Complications of diabetes affect many body systems

• The two types of diabetes are• Type 1 - characterized by insulin deficiency• Type 2 - known as insulin-resistant diabetes

(cells cannot respond to the insulin in the body)

Plasmafatty acids

VentilationMetabolicacidosis

Tissueloss

Substrate forATP production

Urineacidification

andhyperkalemia

Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction

GlycogenolysisGluconeogenesis

Glucose uptake(muscle and adipose)

Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids

Amino aciduptake bymost cells

Brain interpretsas starvation

PolyphagiaHyperglycemia

Glucosuria

Exceeds renalthreshold for glucose

Osmotic diuresisand polyuria

Glucose utilization

No insulin released

Circulatoryfailure

Coma ordeath

Blood volume andBlood pressureLactic acidproduction

Anaerobicmetabolism

Dehydration

Polydipsia

Attempted compensationby cardiovascular

control center

Thirst

ADH secretion

compensationfails

Tissueloss

Protein breakdown,

especially muscle

FAT METABOLISM GLUCOSE METABOLISM PROTEIN METABOLISM

DEHYDRATIONMETABOLIC ACIDOSIS

ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS

Acute Pathophysiology of Type 1 Diabetes Mellitus

• Overview• See pages

743 - 745

Figure 22-16

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Plasmaamino acids



Figure 22-16 (1 of 8)


1 - Absorption of nutrients is normal

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids


No insulin released

Tissueloss

Protein breakdown,

especially muscle



Figure 22-16 (2 of 8)


2a (protein) - Most cells unable to absorb nutrients shift to fasted state metabolism

Plasmafatty acids

Tissueloss


Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction

Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids


No insulin released

Tissueloss

Protein breakdown,

especially muscle



Figure 22-16 (3 of 8)


2b (fat) - Most cells unable to absorb nutrients shift to fasted state metabolism

Plasmafatty acids

Tissueloss


Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction



Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids


Hyperglycemia

Glucose utilization

No insulin released

Tissueloss

Protein breakdown,

especially muscle



Figure 22-16 (4 of 8)


3 - Hyperglycemia results when liver cells also shift to the fasted state, and produce more glucose!

Plasmafatty acids

Tissueloss


Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction



Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids




Glucose utilization

No insulin released

Tissueloss

Protein breakdown,

especially muscle



Figure 22-16 (5 of 8)


3b – More glucose results in polyphagia

Plasmafatty acids

Tissueloss


Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction



Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids




Glucosuria



Glucose utilization

No insulin released

Tissueloss

Protein breakdown,

especially muscle



Figure 22-16 (6 of 8)


4a - Hyperglycemia results in glucose in the urine and increased urine production

Plasmafatty acids

Tissueloss


Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction



Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids




Glucosuria



Glucose utilization

No insulin released

Blood volume andBlood pressure

Dehydration

Polydipsia


control center

Thirst

ADH secretion

Tissueloss

Protein breakdown,

especially muscle


DEHYDRATION


Figure 22-16 (7 of 8)


4b – And then low blood pressure as a result of dehydration

Plasmafatty acids

VentilationMetabolicacidosis

Tissueloss


Urineacidification

andhyperkalemia

Fatbreakdown

Fatstorage

Plasmafatty acids

Mealabsorbed

Plasmaglucose

Liver

Ketoneproduction



Substratefor ATP

production

Plasmaamino acids

Plasmaamino acids




Glucosuria



Glucose utilization

No insulin released

Circulatoryfailure

Coma ordeath

Blood volume andBlood pressureLactic acidproduction

Anaerobicmetabolism

Dehydration

Polydipsia


control center

Thirst

ADH secretion

compensationfails

Tissueloss

Protein breakdown,

especially muscle


DEHYDRATIONMETABOLIC ACIDOSIS


Figure 22-16 (8 of 8)


5 - Metabolic acidosis results, which if untreated can lead to coma and/or death

Type 2 Diabetes

• Accounts for 90% of all diabetics• Insulin resistance (target cells do not respond

normally)• Early symptoms are mild, but later

complications include atherosclerosis, neurological changes, renal failure, and blindness

• Therapy• Diet and physical exercise• Drugs

Glucose Tolerance Test

Figure 22-17

Drugs Attempt to Treat Diabetes by Varying Mechanisms

Table 22-6

Metabolic Syndrome - Insulin resistance syndrome

• Patients have combined symptoms of type 2 diabetes, atherosclerosis, and high blood pressure

• Diagnostic criteria - three or more of• Central (visceral) obesity• Blood pressure ≥ 130/85 mm Hg• Fasting blood glucose ≥ 110 mg/dL• Elevated fasting plasma triglyceride levels• Low plasma HDL-C levels

Fats

• Assembled into chylomicrons in SI lining• Into lymphatics to blood to liver• Liver processes into lipoproteins LDL’s• LDL’s to cells for use in synthesis of cholesterol• Likely leads to atherosclerosis

• HDL’s depleted of cholesterol tend to return to liver for processing into bile for excretion – lowers cholesterol

• HMG coA reductase inhibitors – Big $$• statins – lipitor lovastatin also other cholesterol

treatments: fibrates and niacin

Fat catabolism• Ketosis• Excessive leads to metabolic acidosis• FA catabolized into ketone bodies two carbons

at a time – ß - oxidation

Body Temperature: Energy Balance in the Body

Figure 22-18

DIET• Hunger/appetite• Satiety• Social and

psychologicalfactors

ENERGY INPUT ENERGY OUTPUT

HEAT (~50%) • Unregulated • Thermoregulation

WORK (~50%)• Transport across membranes • Mechanical work Movement• Chemical work

• Synthesis for growth andmaintenance

• Energy storage• High-energy phosphate

bonds (ATP,phosphocreatine)

• Chemical bonds(glycogen, fat)

Radiation

Body heatConduction Conduction

Convection

Internalheat

production

Frommetabolism

From musclecontraction

Regulated processesfor temperature homeostasis

Shiveringthermogenesis

“Wasteheat”

“Wasteheat”

? Nonshiveringthermogenesis

Radiation

Evaporation

EXTERNAL HEAT INPUT + INTERNAL HEAT PRODUCTION = HEAT LOSS

heat lossheat input

Body Temperature: Heat Balance in the Body

Figure 22-19

heat production

Body Temperature: Thermoregulatory Reflexes

Figure 22-20 (1 of 2)

Body Temperature: Thermoregulatory Reflexes

Figure 22-20 (2 of 2)

Mechanisms of Body Temperature Regulation

• Neural control of cutaneous blood flow alters heat loss through the skin

• Sweat contributes to heat loss• Heat production• Voluntary muscle contraction and normal

metabolism• Regulated heat production• Shivering versus nonshivering thermogenesis

Homeostatic Responses to High Temperature

Figure 22-21 (1 of 2)

Homeostatic Responses to Low Temperature

Figure 22-21 (2 of 2)

Regulation of Body Temperature

• Our hypothalamic thermostat can be reset• Typical physiological variations• Fever occurs when pyrogens reset the thermostat

• Pathological cases of altered body temperature• Hyperthermia - compare

• Heat exhaustion• Heat stroke

• Heat exhaustion is characterized by significant sweating, loss of color, cramps, fatigue, fainting and dizziness.

• Heat stroke symptoms include a body temperature over 103, dry skin, high heart rate, confusion and even unconsciousness

• Malignant hyperthermia• Hypothermia

• Diving reflex √

Summary

• Appetite and Satiety• Feeding and satiety centers, glucostatic versus

lipostatic theories, regulation of food intake by numerous regulatory peptides

• Energy Balance• Definition of energy balance, bodily uses for

energy, direct calorimetry, oxygen consumption, RQ, RER, BMR, diet-induced thermogenesis, glycogen and fat as two major forms of stored energy

Summary

• Metabolism• Anabolic pathways versus catabolic pathways,

fed state versus fasted state, glycogenesis, glycogenolysis, and gluconeogenesis

• Chylomicrons, lipoprotein lipase, apoproteins A and B, LDL-C, risks factors for heart disease, beta oxidation and ketone bodies

Summary

• Homeostatic Control of Metabolism• Ratio of insulin to glucagon, Islets of

Langerhans, insulin-receptor substrates, major targets and effects of insulin, glucagon and the fasted state, diabetes mellitus, and metabolic syndrome

• Regulation of body temperature• Hypothalamic thermostat, routes and

mechanisms of heat loss, shivering thermogenesis and nonshivering thermogenesis

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Chapter 22b

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