THIRD EDITION

HUMAN PHYSIOLOGY
AN INTEGRATED APPROACH
Dee Unglaub Silverthorn, Ph.D.

Chapter 22
Metabolism and Energy Balance

PowerPoint Lecture Slide Presentation by

Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University
Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings

About this Chapter

How energy is distributed and used in humans

How nutrients are converted to the energy and
building blocks for synthesis
How hormones control metabolic processes
How the body maintains a constant temperature

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Body Energy: Eating Controls

Cortex "hunger"
CNS Feeding center
CNS satiety center
CNS & GI peptides
Ghrelin
Leptin
CCK
CRH
Neuropeptide Y
Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings

THIRD EDITION

HUMAN PHYSIOLOGY
AN INTEGRATED APPROACH
Dee Unglaub Silverthorn, Ph.D.

PowerPoint Lecture Slide Presentation by

Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University
Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Body Energy: Input = Output (+ storage)

Energy for temperature regulation heat
Energy for metabolic processes work
Transport work move molecules
Mechanical work muscle contraction
Chemical work synthesis & storage
Energy use is measured by oxygen consumption
Calories in food (kilocalorie = 1L H2O 1C)
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Respiratory Quotient

RQ= The ratio of Pure CO2 produced to O2

consumed
For Pure Carbohydrate Catabolism: RQ= 1.0
For Pure Protein Catabolism: RQ= 0.8
For Pure Fat Catabolism: RQ= 0.7

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Changes in Metabolic Rate

Basal metabolic rate (BMR)
Modifying factors
Age & gender
Lean muscle mass
Physical activity level
Diet
Hormones

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Summary of Metabolic Conversions of Nutrients

Nutrients are used, or stored

In general glucose, fats & AAs can be
interconverted

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Summary of Metabolic Conversions of Nutrients

Figure 22-2: Summary of metabolism

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Metabolic Proscesses: Reversible Conversions

Glycogenesis (glucose to glycogen)

Glycogenolysis (glycogen to glucose)
Gluconeogenesis (amino acids to glucose)
Lipogenesis (glucose or FFAs to fats)
Lipolysis (fats to FFAs & glycerol)

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Metabolic Energy Production: Review & Overview

Reactants: glucose
Glycogen, FFAs
Amino acids
Phosphoylation
Glycolysiscytoplasm
2 ATPs, anaerobic
Citric Acid Cycle-2 ATPs, mitochondria, aerobic
Electron Transport system
High energy e-, 32 ATPs
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Metabolic Energy Production: Review & Overview

Figure 22-3: Summary of biochemical pathways for energy production

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Fed State or Absorptive Metabolism: Anabolic

Processes

Reversible pathways shift to anabolic processes

Carbohydrates energize synthesis & storage
Amino Acids built into proteins, surplus stored

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Fed State or Absorptive Metabolism: Anabolic

Processes

Figure 22-4: 4 Dual (push-pull) control of metabolism

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Fat Metabolism: Long Term Nutrient Storage

In adipose cells
In blood: HDL, LDL
FFAs, cholesterol
(plaque build up)
Conversion in liver
Excreted in bile
Used for energy & synthesis

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Fat Metabolism: Long Term Nutrient Storage

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Figure 22-5: Transport and fate of dietary fats

Fasted State or Post-Absorptive Metabolism:

Catabolic

Pathways shift to maintain energy for metabolism

Storage glucose in blood organs in need

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Fasted State or Post-Absorptive Metabolism:

Catabolic

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Figure 22-6: Fasted-state metabolism

Pancreatic Hormones, Insulin & Glucagon Regulate

Metabolism

Beta cells produce insulin cellular uptake of

blood glucose
Alpha cells produce glucagon blood glucose
(from cells)
D cells produce somatostatin gastric secretion

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Pancreatic Hormones, Insulin & Glucagon Regulate

Metabolism

Figure 22-7 b: The endocrine pancreas

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Pancreatic Hormones, Insulin & Glucagon Regulate

Metabolism

Figure 22-8: Metabolism is controlled by insulin and glucagon

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Lipohypertrophy in a Patient

A 55-year-old man with a 31-year history of type 1 diabetes mellitus presented

for a routine clinical evaluation, his first in two decades. His insulin regimen
consisted of a combination of neutral protamine Hagedorn (NPH) and rapidacting insulin. In the many years since his diabetes diagnosis, he had habitually
injected insulin into two locations in the periumbilical region. Two discrete
subcutaneous masses were palpated. Both masses were firm and pendulous. A
clinical diagnosis of insulin-induced lipohypertrophy was made. This condition
has been documented with many insulin preparations. Careful attention should
be paid to the teaching of correct methods of insulin injection, site rotation, and
routine inspection of injection sites. Lipohypertrophy can be associated with
glycemic flux and can be disfiguring. The patient was counseled regarding
injection-site rotation and encouraged to use a 6-mm rather than an 8-mm
needle. NPH was replaced with insulin glargine. The patient was subsequently
lost to follow-up.

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Insulin Action on Cells:

Dominates in Fed State Metabolism

glucose uptake in most cells

(not active muscle)
glucose use & storage
protein synthesis
fat synthesis

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Insulin Action on Cells:

Dominates in Fed State Metabolism

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Figure 22-10: Insulins cellular mechanism of action

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Insulin: Summary and Control Reflex Loop

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Figure 22-13: Fed-state metabolism

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Relationship between HbA1c and

average finger blood glucose
HbA1c of
HbA1c of
HbA1c of
HbA1c of
HbA1c of

9%
8%
7%
6%
5%

=
=
=
=
=

260 mg/dl (14.4 mmol/l)

220
(12.2
)
180
(10.0
)
140
(7.7

)
100
(5.5

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Glucagon Action on Cells:

Dominates in Fasting State Metabolism

Glucagon prevents hypoglycemia by cell

production of glucose
Liver is primary target to maintain blood glucose
levels

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Glucagon Action on Cells:

Dominates in Fasting State Metabolism

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Figure 21-14: Endocrine response to hypoglycemia

Diabetes Mellitus: Abnormally Elevated Blood

Glucose (Hyperglycemia)

Type 1: beta cells destroyed- no insulin

producedchronic fasted state, "melting flesh",
ketosis, acidosis, glucosurea, diuresis & coma

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Diabetes Mellitus: Abnormally Elevated Blood

Glucose (Hyperglycemia)

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Figure 22-15: Acute pathophysiology of type 1 diabetes mellitus

Diabetes Mellitus: Type II a Group of Diseases

Over 15 million diabetics in USA- 10% type I,
90% type II
Insulin resistance keeps blood glucose too high
Problem with receptors, glucagons levels
Chronic complications: atherosclerosis, renal
failure& blindness

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Diabetes Mellitus: Type II a Group of Diseases

Figure 22-16: Normal and abnormal glucose tolerance tests

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Energy Balance: About 50% used for Body Heat

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Figure 22-17: Energy balance

Body Temperature Balance: Homeothermic

Metabolic heat production usually required to

maintain balance
Balance is very narrow range, usually higher than
environment

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Body Temperature Balance: Homeothermic

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Figure 22-18: Heat balance

Thermoregulation:
Homeostatic Balancing of Body Temperature
Peripheral and body core receptors senses
change
Hypothalamic thermoregulatory center
integrates & initiates:
Shivering, non-shivering thermogenesis,
vasoconstriction

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Thermoregulation:
Homeostatic Balancing of Body Temperature

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Figure 22-19: Thermoregulatory reflexes

Thermoregulation: Prevention of Overheating

Sweat: evaporates from skin cooling

Vasodilation of cutaneous vessels transports heat
from core
Behavior: activity, exposure to heat

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Thermoregulation: Prevention of Overheating

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Figure 22-20: Homeostatic responses to environmental extremes

Thermoregulation: Pathologies
Hyperthermia: body temperature too high
Fever: pyrogens fight pathogens
Heat exhaustion (1020F)
Heat stroke (1060F) death
Malignant hyperthermia defective Ca++
release
Hypothermia: body temperature too low
Metabolism slows loss of consciousness,
death
Surgical applications: heart surgery
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Malignant Hyperthermia

Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic

disorder of skeletal muscle calcium regulation associated with
uncontrolled skeletal muscle hypermetabolism. Manifestations of
malignant hyperthermia (MH) are precipitated by certain volatile
anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane,
enflurane), either alone or in conjunction with a depolarizing muscle
relaxant (specifically, succinylcholine). The triggering substances release
calcium stores from the sarcoplasmic reticulum and may promote entry
of calcium from the myoplasm, causing contracture of skeletal muscles,
glycogenolysis, and increased cellular metabolism, resulting in
production of heat and excess lactate. Affected individuals experience:
acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity,
compartment syndrome, rhabdomyolysis with subsequent increase in
serum creatine kinase (CK) concentration, hyperkalemia with a risk for
cardiac arrhythmia or even arrest, and myoglobinuria with a risk for
renal failure. In nearly all cases, the first manifestations of MH
(tachycardia and tachypnea) occur in the operating room; however, MH
may also occur in the early postoperative period. There is mounting
evidence that some affected individuals will also develop MH with
exercise and/or on exposure to hot environments. Without proper and

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Malignant Hyperthermia: Molecular Genetic Testing

To date, only two genes in which mutation causes MHS have been
identified:

RYR 1 (MHS1 locus) encodes the type 1 ryanodine receptor of skeletal

muscle. Molecular genetic testing indicates that mutations in RYR1 are
identified in up to 70%-80% of individuals with confirmed MHS [
Sambuughin et al 2005, Galli et al 2006, Robinson et al 2006,
Kraeva et al 2011].

CACNA1S (MHS5 locus) encodes the 1-subunit of the skeletal

muscle dihydropyridine receptor L-type calcium channel. Mutations in
CACNA1S account for 1% of all MHS [Stewart et al 2001].

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Summary
Eating provides carbohydrates, proteins, & fats
for metabolism
Reversible reactions allow interconversion of
nutrients
Energy is used for body heat and work: transport,
synthesis, storage
Metabolic rate changes with age, sex, body fat,
activity & diet
Insulin regulates anabolic cell activities & glucose
uptake in cells
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Summary

Glucagon regulates catabolic reactions & prevents

hypoglycemia
Diabetes is a major disease associated with insulin
lack or tolerance
Maintaining homeothermy takes 50% of our
energy
Hypothalamic thermoregulatory center controls
heat homeostasis

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