theory 50% lect+tut+hot topics Flashcards
what is energy
Energy is the property of matter allowing it to be
transformed either by doing or accomplishing work
what r the forms of energy
� Solar � Chemical � Mechanical � Electrical � Thermal)
describe the first law of thermodynamics
Fundamental biological principle
energy is not produced, consumed,
or used up. It is merely transformed
from one form into another,
describe the second law of thermodynamics
The transformation of energy is always in the direction of a continuous increased universe entropy
what is energy metabolism
� The ways in which the body obtains and spends energy
from food
why do we need energy
� Energy in food is chemical energy which we absorb and
convert into other forms of energy
� Chemical: synthesis of new molecules
� Mechanical: muscle contraction
� Electrical: ionic gradients, neurotransmission
� Thermal: dissipation as heat
� All forms of biological work are powered by the direct transfer of chemical energy
how to get energy
Food is a source of chemical energy
Macronutrients in food can be combusted to liberate energy
Food + O2 -> H2O + CO2 + Energy as heat
what is a joule or a calorie
A joule or a calorie is a measure of energy for both
food and physical activity
what is the definition for Calorie
A Calorie is the amount of heat required to increase 1 kg of water
by 1 degree cenUgrade (1 kcal = 1 Calorie = 1000 calories)
what is definition for joule
A joule is the energy used when 1kg is moved 1m by a force of 1 newton
what is the conversion for 1 Calorie
1 Calorie (kcal) = 4.184 KILOJOULES (kJ)
what do we do with the energy from the food?
the total food energy (gross energy) 100%, 1-9% is non-digestable energy and excreted in faeces. 95% of the gross energy change to metabolisable energy and small amount lost in urine and sweat. 25%-40% of the metabolisable energy is used to do useful work, 5% thermic effect of food and 50% lost as heat.
what percentage of the nergy from 1 mole of glucose trapped in the form of ATP?
- Energy released as heat when 1mole glucose (180gm) is combusted
- # moles ATP generated from 1mole glucose in body = 32 • Energy equivalent of 32moles ATP = 1600 kJ
- % of energy from 1 mol glucose in form ATP = 56%
how did the gross energy determined
by bomb calorimeter
what is the metabolisable energy equivalent to
net value to body
why the energy from protein net value to body is much more less than gross energy
lost as urea.
what is the equation for En (energy intake)
En = En(out)+- En(stored)
energy intake= energy expenditure +- adipose tissue
can BMR be measured accurately?
NO, it need to be stable, not emotional aroundal, cannot be sick, nothing else going on in the body, fasting state etc. in daily life, we measure the Rest Metabolic Rate
what r the components of Daily Energy Expenditure?
15%++ will be activity, 10-15% used as thermic effect of food.
60-70% used as BMR which includes arousal and sleeping metabolic rate
how to Estimating energy requirement
• Calculate energy intake
very imprecise due to technical problems with measuring intake and under-reporUng
• Estimate BMR and level of physical activity
Prediction equations for BMR and estimate level of physical activity
• Measure BMR by indirect calorimetry and apply estimate of physical acUvity
what r the measurement of energy expenditure
By Direct Calorimetry and Indirect Calorimetry
what does direct calorimetry do
measre heat loss in an airtight chamber
what does indirect calorimetry do
measure oxygen uptake, carbon dioxide production.
1L oxygen consumed at rest = 20.3 kj energy expended
then the RESPIRATORY QUOTIENT (RO) can be measured which is the ratio of VCO2/VO2.
the RQ can tell you the source of the fuel it comes from
what is the the RQ for fat
0.7
what is the RQ for protein
0.81
what is the RQ for CHO
1
what is the RQ for alcohok
0.66
what r the method for non-calorimetric estimate of energy expenditure
- HR
- double- labelled water
- measures of physical activity
- questionnaires
- movement monitors
what is RQ
ratio of VCO2/VO2, it is guide to the mixture of nutrients being oxidised
why HR can be used for estimate energy expenditure?
HR is proportional to O2 consumption, O2 consumption is an indirect way of measure energy expenditure
wwhat r the factors involve in estimating physical activity
MET (Metabolic Equivalent Task) Factor
estimates intensity of a single activity as a multiple of BMR
• PAL (Physical AcUvity Level) Factor
estimates the total daily physical acUvity as a mulUple of BMR
what r the nutrient depletion signals
- appetite
- foraging
- ingestive behavior and
- energy saving
what r the nutrient excess signals
- satiation
2. energy expenditure
what r the factor that the body is able to respond with altered metabolic efficiencies
‘Humans are flexible converters of food energy, able to respond with altered metabolic efficiencies to different diets, environmental conditions, specific tasks and health states’
what is energy homeostasis
energy reserve (body weight) increase or decrease depend on absorption and energy output. absorption of proteins, gats and carbohydrates, these energy used to do physical activity, energy for absorption and nutrient storage and BMR
‘Why can one person live on half the calories of another and yet remain a perfectly efficient machine?’
these depends on factors that influence amount of energy intake and expenditure. which include endogenous and exogenous factors
what are the factors that influence amount of energy intake and expenditure?
- endogenous
- biological and psychological (cognitive) - exogenous
what are the endogenous factors that influence amount of energy intake and expenditure?
-biological
-psychological (cognitive)
biological include:
1. appetite/hunger (the desire to eat)
2. satiation (the signal to bring eating to an end)
3. satiety (the suppression of appetite/ hunger)
4. basal metabolic rate ( body composition, age etc)
5. thermic effect of food (energy expended to digest and absorb nutrients)
6. phyical activity
what r the exogenous (environmental ) factors that influence amount of energy intake and expenditure?
- physical (e.g. music pace)
- social
- economic
what factors affect BMR
- genes (determine gender, which in turn determine the body composition )
- height, weight
- gender
- metabolic changes (lactation, pregnancy, growing, disease state)
- age
- percent fat vs muscle
- surface area
- climate
- hormone
- drugs
what is the approximate BMR age from 20-49 years
women=146 kj/m2/hour
men=159 kj/m2/hour
how does age affect BMR
kids have high BMR per kg body weight, because they r growing and developmenting
- the metabolic rate about orgaans stay the same, the children have high metabolic active organs because they have more fat-free mass contribute to organs .
- the BMR per kg of organ per day stay the same, they chew a lot of energy, as we grow, the organs make less in our body mass.
which organs have high metabolic rate
liver, brain, heart and kidneys have high metabolic rate (kJ/kg/d). however the daily energy expenditure is calculated by metabolic rate x weight. the skeletal, liver, brain and residual mass have high energy usage per day (kJ/d)
Living below the zone of thermal comfort, choices
- Insulate by becoming obese
- Boost BMR to generate more heat
- Cut conductance through vasoconstriction • Create a portable microenvironment
explain Adaptive vasoconstriction of Australian Aborigines
in disert, the aborigines have no difference in BMR overnight, become they dont shiver, their body vasoconstrict, therefore they spend less energy compare to white. the white man have dramatic changes over night for BMR because they shiver
what is energy balance
• Energy balance = balance of energy from protein, fat, carbohydrate
- the energy expenditure is continuum, some energy is stored to maintain this
what is nutrient balance, and what r the possible outcomes
nutrient intake - nutrient utilisation = change in body nutrient reserves
this follow the law of conservation of mass
3 possible outcomes: zero balance, positive balance, negative balance.
what is nitrogen balance
• Nitrogen balance = protein balance
what r the example of nutrient balance
1. low-carb diets: energy balance with - negative car balance - positive fat balance 2. diet negative energy balance 3. pregnant positive balance most nutrients 4. growth in childhood positive energy balance positive nitrogen balance 5. illness and severe trauma negative energy balance negative nitrogen balance
what is nutrient turnover e.g.protein
Most metabolic substrates are being continually utilised and replaced
e.g. protein in diet -> amino acid metabolism in tissue-> urea synthesis for excretion
the amino acid metabolism in tissue and body protein are continuous turnover
what is glucose turn over
the glucose level is dynamic steady state. the insulin is secreted to maintain blood glucose level after a meal/
what happen in fed to fasted state
fed state: beta cell increase amylin, and insulin, alpha cell decrease glucagon.
glucagon and insulin send signal to liver to decrease glucose production, therfore decrease glucose from the liver to Blood vessel
fastinf state: glucagon secreted, decrease insulin, gluconeogenesis-> increase glucose production, glycogenolysis -> change to glucose
this will increase glucose production, therefore maintains glucose in blood stream
what is flux
FLUX = rate of flow of a nutrient through a metabolic pathway
eg the flux of glucose from blood to tissues = 2mg/kg body weight/min • blood glucose stays steady because liver matches glucose production
• Net flux = 0
• Cellular, tissue or whole body level
• Dependent on the metabolic pool source of the nutrient
what r the types of metabolic pools
3.
1.Precursor pool
• Provides substrate from which the nutrient/metabolite is
synthesised
2. Functional pool
• Nutrient/metabolite has direct role in one or more bodily functions
3. Storage pool
• Buffer of nutrient/metabolite that can be made available for the functional pool
what is precursor pool
• Provides substrate from which the nutrient/metabolite is synthesised
what is functional pool
• Nutrient/metabolite has direct role in one or more bodily functions
what is storage pool
• Buffer of nutrient/metabolite that can be made available for the functional pool
what r theavailable energy from energy reserves and from which source
- available energy can be synthesized in the liver and muscle to form glucose/glycogen
- adipose makes triglyceride, which can be used as energy source
- muscle have mobilisable protein which can be used for energy
what r the regulatory mechanisms
Regulatory mechanisms in the body manage to store excess food energy and release it as we need it.
• Nervous system - Central nervous system • Endocrine systems - Hormonal control
what r the pancreas hormone
alpha cells secrete glucagon, beta cellls secrete insulin and amylin
what is insulin
• Peptide hormone
• Synthesised as preproinsulin
• Secreted as two peptide chains (A & B)
linked by disuphide bond
• Secretion regulated by plasma glucose
concentration, amino acids
• Insulin stored in secretory granules and released by exocytosis
how is insulin made
- insulin is made firstly with preproinsulin which is A chain and B chain
- preproinsulin convert to proinsulin. the A chain connected to B chain by a connecting peptides which is called C chain
- then the C chain is cleaved off in the secretory granules, insulin is secreted in the active form
what is glucagon
• Single polypeptide chain synthesised as proglucagon, then in the pancreas, glucagon is secreted.
what does glucagon do
• Major action is to elevate blood glucose levels
what stimulate and suppress glucagon
- Stimulated by low glucose and high amino acids
* Suppressed by rise in blood glucose concentration
how does glucagon work
- Main target tissue liver – 5-10% removed in first passage
* Binds glucagon receptor, works via activation of adenylyl cyclase and cAMP second messenger
describe the regulation of glucose level in blood
- the plasma glucose conc. is changing with the meal
- insulin is secreted to reduce the flutuation of the blood glucose
- glucagon is secreted in the fasting dips to make sure blood glucose level dont drop too far
what is the short term effects of cortisol
• Short term effects • Mediated through changes in protein synthesis (hours) • Fat mobilisation (increases HSL) • GNG(gluconeogenesisi) • Reduced muscle glucose uptake • Increase muscle protein breakdown
what is long term effects of cortisol
• Sets the tone of response to
other hormones
• Permissive effects
what is leptin
secrete from fat tissue
- reflect how much fat we have in the body
- directly tell the brain to stop eating
- increase energy expenditure in mice,
What is body composition?
› The proportion in which chemical components contribute to body mass
› Determined by the interaction between genetics and nutrition
Why is body composition important?
› Nearly every aspect of clinical nutrition and exercise science uses body composition research
› Body composition changes with growth, development, pregnancy, lactation, ageing, exercise and disease
› Abnormal body composition is associated with disorders and disease
› Body composition is highly variable between individuals
what r the levels of body composition
- atomic
- molecular
- cellular
- tissue/organ
- whole body
what does atomic level include for body composition
oxygen, carbon, hydrogen, nitrogen, calcium, phosphorus
what does molecular level include for body composition
Over 100 000 chemical compounds › Water – extra- / intracellular ~60% › Lipids - ~17% › Protein - ~17% › Carbohydrates – mainly glycogen › Minerals – bone & soft tissue
what does cellular level and tissue level include for body composition
Cellular › Body cell mass – 10^18 cells › Extracellular fluids › Extracellular solids Tissue ->Body weight = adipose Ossue + skeletal muscle + bone + organs + ...
what does whole body level include for body composition
10 dimensions generally considered
- Stature – indicates general body size and skeletal length
- Segment lengths of limbs
- Body breadth – measures of body shape, skeletal mass and frame size
- Circumferences eg waist circumference indicator of adiposity
- Skinfold thickness – for esOmaOng fatness and distribuOon of subcutaneous fat
- Body surface area – used to esOmate basal metabolic rate
- Body volume – indicates body size and used to determine body density
- Body mass
- Body mass index (BMI) body mass (kg)/height m2
- Body density used to indirectly determine fat free mass
what r the types of method for body composition analysis
- direct
- indirect
- double direct
what measurement are direct method for body composition
- Carcass analysis
- in vivo neutron activation analysis
what measurement are indirect method for body composition
- densitometry
- deuterium oxide dilution
- radioactive potassium ^40 counting
- more compartment models
- dual energy X ray
- absorptiometry
- CT/MRI scans
what measurement are double indirect method for body composition
- weight/height indices
- skinfolds/ultrasound
- circumference/diameter
- impedance
- infrared interactance
- creatine excretion
give an e.g. of densitometry
hydrodensitometry
what is hydrodensitometry
it is an indirect measurement od body composition
› Based on Archimedes principle:
- volume of object = volume water displaced
- Underwater weighing
density of fat=0.9 g/cm^3
density of fat-free =1.100g/cm^3
known the equation for densitometry
slide 12 L4
what is air displacement method
it is an indirect measurement of body composition, belong to densitometry.
using body pod.
Bod Pod
Two chambers (test, reference) separated by diaphragm
Pressure of air increased by adding a known volume of air into chamber.
Based on Boyle’s law to calculate volume: P1/P2 = (V2/V1)
know the equation for total body water
slide 15 and 16 L4
what is total body potassium
it is an indirect method for measuring body composition .
Also used to determine fat free mass. Potassium is present within cells but not associated with stored fat.
40K natural isotope of potassium (0.012% of all K), emits γ rays Measurement of 40K radiation from the body for TBK
K in lean mass is variable and dependent on sex, age and BMI. Assume men: 60 mmol / kg FFM
women: 66 mmol / kg FFM
what is imaging techniques
it is an indirect method for measuring body composition .
give and e.g. of imaging technique for measuring body composition
DEXA
Dual-energy x-ray absorptiometry
Body is scanned with x-rays of 2 distinct energy levels
The amount of energy not absorbed by tissues is detected by photocells
Tissue absorption of radiation is determined by its chemical composition – allowing us to distinguish between bone, lean tissue and adipose.
what include in the anthropometry
Common measures › BMI = Body mass index mass (kg) height (m) › Waist, hip circumference › Skin fold thickness
how to calculate BMI
= weight(kg)/height(m^2)
Healthy weight range is usually defined in terms of body mass index (BMI)
normal between 18.5 -24.9
what is waist circumference for? and the range for men and women
it is a surrogate marker of visceral fat.
men, greater than 102 cm=increased risk
women, greater than 88 cm=increased risk
what is the risk of high and low BMI
high BMI have very high motality ratio due to cardiovascular and gallbladder disease and diabetes mellitus
low BMI have moderate motality ratio due to digestive and pulmonary disease
Factors influencing BMI
› Ethnicity › Gender › Age › Body build › Epigenetics
› Body composition changes during intrauterine & postnatal growth
› Body composition can be changed by malnutrition and disease
› Most methodologies are indirect and rely on established assumptions which may not be correct for all populations
› The most variable component of body composition is fat mass
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wht kind of system is epigenetic gene regulation
Epigenetic gene regulation is a binary system: “On” or “Off”
Epigenetic states are probabilistic – every locus has some probability of being silent
what does nucleosome packaging do in epigenetic
nucelosome packaging determines chromatin structure and transcription state
what does epigenetic modification allow
Epigenetic modifications allow cells with precisely the same genomes to adopt a multitude of phenotypes based on the
activity of some loci and the silencing of others
-Cell differentiation is epigenetic gene regulation par excellence
~25,000 genes in human genome – each cell type uses only a proportion, and the remainder are silent
what is epigenetic modification
Epigenetics is interposed between genes and environment
-Epigenetic modifications mediate genome function and are responsive to environmental cues: cellular, organisismal, external
what influence the probability of epigenetic erro
The probability of epigenetic errors may be influenced by the environment and the most vulnerable time is during our development when cellular epigenotype is set
what does nutritional stress do in their offspring
The intrauterine environment is inescapable: nutritional stress during gestation can have life-long health consequences
- a baby with low birth weight is more likelt to develop hypentension and CVD in the late middle age
you are what your mother ate
We now know that undernutrition, overnutrition, or an altered supply of key nutrients during gestation can all induce metabolic syndrome and other symptoms in offspring: this effect is called FETAL PROGRAMMING, or developmental origins of health and disease
- adverse fetal environment followed by plentiful food in adulthood maybe a recipe for adult chronic disease.
he rate of obesity is rising …
an increase number of women are going into pregnancy overweight or obese
an increase number of overweight and obese men are fathering children
Maternal obesity and/or gestational diabetes program a range of health effects in offspring
- Overnutrition as well as obesity per se
- Periconceptional period may be as
important as gestation - Metabolism not the only trait affected
periconceptional period: the time that the oocyte is maturing 1 or 2 month before ovulation through to conception implaintatio
How can an environmental insult sustained in utero persist throughout life to manifest as a health effect in adulthood?
… Epigenetic changes to gene expression
how to Creating an epigenotype
A sophisticated program that usually goes according to plan
How can two specialised cells (sperm and ova), with their own specific phenotypes and epigenotypes, come together to create a totipotent zygote?
What mechanisms are in place to avoid epigenetic errors being propagated to offspring?
epigenetic flux through out the life cycle
- once the fertilization happens. the first embryooic epigenetic resetting take place, the male genome rapidly demthylated and female demethylated at a slower rate. This allows
1. Restoration of pluripotency 2. Embryonic gene expression
3. Early lineage development
4. Parental imprinting marks spared - at theblastocyst stage, a second round of epigenetic resetting take place. this allow:
“Clean the slate” for the next generation – remove epimutations, set germ-cell specific marks
Parental imprints erased and reset
what is epimutation,
aberrant epigenetic silencing of a normally active gene
or, occasionally, aberrant activation of a normally silent gene
what background does epimutation occurs
This epimutation occurs on a uniform genetic background
is epimutation common in cancer
yes. Epigenetic dysregulation is a hallmark of cancer
- cancer cell methylate and silence a lot of genes that cancer cell dont want to be active e.g. mutation repair gene, apoptosis gene and any gene cause cancer cell to shut off
- retrtransposon often activated to cause more mutation in the cancer cells > they are jumping gene cause more mutation in the genome
epimutation as the primary genetic leision in familial cancer
familial cancer: germline mutation that passes from parent to children, they have predisposition for cancer around age 50 years old.
- some member in family look like they have the sydrome but have no mutation in DNA.
- 1 pair of mismatching gene called MLH1 has silenced in everycells in his body by methylation .
Epimutations can sometimes be inherited between generations. what kind of inheritance?
Non-mendelian inheritance of the MLH1 germline epimutation in humans
- epigenetic resetting in the germline is there to wipe off epigenetic mistake, it’s clearly it doesnt work all the time.
what is Transgenerational epigenetic inheritance
Transgenerational epigenetic inheritance
The transmission of an allele’s epigenotype through MEIOSIS –
so that the epigenotype of the offspring resembles that of the parent.
Importantly, this does not generally occur in lockstep with the inherited genotype, so the
pattern of inheritance is NON-MENDELIAN
Epigenetic inheritance has been recognised for some time in plants :
- Paramutation
* Transposon silencing
Epigenetic inheritance in animals
Epigenetic states are generally reset between generations
Some sequences escape resetting
e.g. centromeres, some retrotransposons
… any genes?
Epigenetic inheritance in animals: the first reports
- Inheritance of Fab7 activity in Drosophila Melanogaster
- Inheritance of gene expression changes in mice after embryo manipulation (also the first instance of inherited environmental effects – more on this in a minute!)
- Inheritance of transgene silencing in mice – several reports
Agouti viable yellow (Avy) mice:
a model of epigenetic variation, and inheritance
- an insertion of transposon upstream of agouti coat colour gene.
- Avy is epigenetically regulated
- Activity/silence correlates with DNA methylation at the IAP promoter region
is Avy epigenotype heritable
Avy epigenotype is partially heritable – but only when maternally transmitted
Are epimutations induced by our developmental environment – and are they inherited?
Avy mice are also a model of epigenetic response to early environment
- Gestational exposure to various nutritional stressors alters the spectrum of offspring coat colour phenotypes
- he epigenetic effect of methyl donor supplementation on Avy is heritable: you are what your grandmother ate!
- The epigenetic effects of maternal undernutrition may be heritable also
what is the paternal effect on epigenetics inheritability
Paternal effects: intergenerational transmission of father’s condition
- if thefather have diabetes, the children is smaller.
- the birth weight predict T2D in later life
Paternal undernutrition and overnutrition can each program metabolic defects in offspring
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Yellow Avy mice as a model of natural-onset obesity and type 2 diabetes
Yellow Avy mice are obese and insulin resistant but not frankly diabetic, mirroring the phenotype of most obese individuals (particularly men) of reproductive age
-Obese Avy parents induce metabolic defects in their wild-type offspring
Offspring of obese mothers show DNA methylation and gene expression changes across their genomes
T
Does maternal obesity affect more than one generation – is the altered phenotype heritable?
We have recently used Avy to model paternal obesity and find that both sons and grandsons of obese males are similarly predisposed to metabolic dysfunction. We find epigenetic changes in their SPERM!
The legacy of parental obesity
- Both maternal AND paternal obesity programs an increased disease risk in offspring, independently of the inherited DNA sequence, that can be passed on to subsequent generations.
- Programming is associated with widespread gene expression and epigenetic changes – these are likely maladaptive changes for the individual, and may be linked to deleterious phenotypes beyond metabolism.
epigenetic and advice
- Having an obese parent – or grandparent – predisposes to metabolic disease.
- Predisposed individuals can propagate the latent metabolic phenotype even if they themselves do not exhibit metabolic disease.
- Maintaining a healthy diet prevents the onset of overt disease in programmed individuals; exposure to a Western diet exacerbates the deleterious health effects.
what is Nutrition status
Often an ill-defined term – usually assumed someone is well nourished / has
good status unless clinically defined as deviating from this
how do u determine nutrition status
For determining nutrition status (or nutrition problems) a comprehensive
history may include:
1. › Physical examination
- Anthropometric measures (ht/wt, wt changes (how much, over how long, why)
- Fat / muscle stores
2. › Intake
- Diet history / food records / … ie some kind of assessment of dietary intake,
comparing this to known reference standards
- RDIs for age/sex
- Estimated protein / energy requirements
- ?AGHD/ food groups
3.› Biochemistry
- Eg iron status, and many other parameters – variable
4.› Functional status
- Ie what is the person able to do, compared with norms, and contributors to any
changes
› Medical history and disease state
what r the Screening and assessment for nutrition status
Screening and assessment tools available for clinical application:
1 - screening tool may be decision tree for referral to dietitian – often done by
nursing or other allied health eg MST
2 - Assessment tools – require dietitian to implement and interpret – used to
diagnose malnutrition in hospitals
3- MNA (mini nutritional assessment)
4 - SGA (subjective global assessment)
› What might lead to undernutrition?
1 - Nutritional crisis, food insecurity à involuntary nutritional inadequacy and starvation (famine)
2 - Illness eg malabsorption of nutrients, drug nutrient interactions, altered metabolic fate of
nutrients, nausea, vomiting, anorexia, cancer cachexia, GIT disorders (eg motility, enzyme
dysfunction, enteropathies, strictures/blockages), etc
3- Anorexia 2o anxiety/stress, altered appetite 2o eg drugs (ADHD meds, etc)
4- Lack of knowledge about good nutrition
5- Eating disorders
6- Drug dependence eg alcohol
7- Increased requirements eg post trauma / surgery, some cancers
Undernutrition may occur in the form of inadequate/absorption/utilisation/excretion of:
- Specific nutrient(s) – quite common!
- Energy
- Protein-energy – common in elderly and marginalised groups
what is the Ramifications of undernutrition in children
› In children
1- Growth retardation / stunting
2- Delayed developmental milestones
3- Diseases of inadequate specific nutrients eg rickets
what is the Ramifications of undernutrition in all
1- Muscle wasting
2- Increased risk infection / pressure wounds 2o compromised immune function
3- Longer healing times
4- Increase risk hospitalisation and length of stay
5- Death
6- Nutrient specific diseases eg osteoporosis, anaemia, etc
7- Diminished cognitive performance
8- Decreased physical ability
9- Decreased quality of life
Cost of malnutrition
1› Massive cost in human terms in some developing countries
2› High personal cost to person in terms of quality of life, their family and
friends, and also to health system
3› Rate of malnutrition in Australian hospitals reported up to 50%
4› Risk malnutrition increases with length of stay
5› ~50% nursing home residents malnourished
Who is at risk of malnutrition in Australia?
1› Elderly esp with co-morbidities
- Eg Parkinson’s, polypharmacy, dementia, COPD
2› Unwell
- Disabled, housebound
- Chewing / swallowing problems
- Cancers
3› Socially disadvantaged, including children from low SES backgrounds,
despite often being overweight
4› Young people esp women with restrictive eating practices
5› Population with psychiatric disorders
hows I refeeding syndrome described first after WWII
many of
whom survived the camps only to die when refed – usually of cardiac failure
what happen When intake becomes severely reduced
In starvation, physiology alters 2degree lack of glucose/energy
1› Insulin levels drop, glucagon increases… glycogen stores utilised and
biochemical shift to gluconeogenesis initially…..
2› Ketones and FFA become main energy source… (initially low ketone body use
peripherally to conserve protein/muscle breakdown)
3› Eventually loss of lean muscle mass occurs
4› Biochemical stability of serum levels of Mg2+, K+, PO4
3- continues, but
intracellular stores (where you would expect the greater concentration)
become depleted as a result of the fat/protein catabolism, and intracellular
volume also shrinks
5› Vitamin losses may become critical, particularly thiamine
6› Urinary losses of minerals such as K+ and Mg2+ are reduced during starvation
what happen to the body in refeeding
Sudden shift from catabolism to anabolism
1 Influx of CHO – becomes major fuel – hyperglycaemia may occur and
insulin induction may lead to a biochemical cascade
2 › Na+-K+ ATPase transporter stimulated by insulin
- à dramatic shift of K+ from extra- to intra-cellular space with H2O shift following
(osmosis)
- Also transports glucose into cells
- Water follows by osmosis
3 › Insulin stimulates glycogen, fat and protein synthesis – requiring
phosphate, Mg2+ and cofactors (eg thiamine)
4 End result? Decreased serum K+/Mg2+/PO4
3-
what is Thiamin
› Coenzyme forms: thiamin pyrophosphate (TPP)
thiamin triphosphate (TTP)
› Coenzyme for decarboxylases eg:
- Oxidative decarboxylation
- In glycolysis and TCA cycle
- Of branched chain amino acids
- Transketolase reactions in the pentose phosphate pathway
what happen when there is lack of thiamin
cause beri beri
why is thiamin important
it is an importan co-facto in Kreb cycle-prosthetic group on pyruvate dehydrogenase
what is RDI of thiamin in adult
› RDI 1.1-1.2mg / day (adults)
› Max ~30mg in body
what r the sources of thiamin
› Sources
- In small but sufficient quantities in most nutritious foods
- High in pork products, sunflower seeds, pasta, bread (mandatory
fortification in Aus)
how stable is thiamin biochemically and in food and its half life
› Biochemically fragile - not stored long term – consumed or
excreted
› In food, may be destroyed by heat, leached into cooking water
(water soluble)
› Half-life: 9-18d
what r the causes of Thiamin deficiency
1› Inadequate intake 2› Chronic alcoholism - Thiamin absorption is impaired - Decreased food intake - Increased excretion 3› High (inadvertant) intake of thiaminase eg raw fish 4› Compromised nutritional intake for a period of time eg some groups of hospitalised patients
what r the syptoms of dry beri beri
Peripheral neuropathy 1› longest nerves affected first long limbs – legs 2› loss of sensation Enlarged heart, cardiac failure Weight loss Muscular weakness - can’t walk, foot drop Poor short term memory
what r the syptoms of wet beri beri
Acute
Oedema
Raised jugular vein pressure
whar Wernicke’s encephalopathy / Korsakoff’s syndrome
› BUT not usually seen with Beri beri
- ?WE/KS more common in those who are less active
- Most commonly seen in alcoholics
whats the symptoms for - Wernicke’s encephalopathy
› Symptoms may include:
- Wernicke’s encephalopathy
- Ocular disturbances (eg nystagmus), ataxia (unsteady stance and gait),
confusion, hypothermia, apathy, coma
whats the symptoms for - Korsakoff’s syndrome
- Korsakoff’s syndrome
- Amnesia
- Confabulation
› Other possible symptoms: hypotension, tachycardia, hypothermia, progressive
hearing loss, epileptic seizures, dementia
what happen to phosphate in starvation
PO43- shift
1 › In starvation, PO4
3- may stay in N range
2› Insulin stimulates cellular uptake of PO4
3- > potentially profound
hypophosphataemia
- NB PO4
3- required for generation of ATP
- Sudden large drops in PO4
3- or a drop below ~.5mM may produce refeeding
symptoms
- eg rhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure,
hypotension, arrhythmias, seizures, coma, sudden death
what happen in potassium when in starvation
potassium K+ shift
1› NB major intracellular cation
2› In starved state serum levels may remain in N range
3› In refeeding, taken up into cells as they increase in volume and number 20
effects of insulin
4› Severe hypokalaemia -> derangements in membrane potentials -> eg
arrhythmia and cardiac arrest
what happen to magnesium when in starvation
1› Also predominantly an intracellular cation
2› Important co-factor in many enzyme systems (including oxidative
phosphorylation, ATP production)
3› Necessary for structural integrity of DNA, RNA, ribosomes
4› Deficiency has an effect on membrane potentials and can lead to cardiac
dysfunction and neuromuscular complications
when happen to glucose when starvation happens
1› After starvation, glucose intake suppresses gluconeogenesis thru insulin
release
2› XS glucose often leads to hyperglycaemia then to osmotic diuresis,
dehydration, metabolic acidosis, ketoacidosis
3› XS glucose may also lead to lipogenesis, fatty liver, increased CO2
production and respiratory failure.
what happen to sodium, N and fluid in starvation
Returning CHO to system can have profound effects on sodium and water
balance
› -> rapid decrease in renal excretion of sodium and water
› If significant fluids are provided for repletion (eg IVF) in order to maintain
normal urine output, fluid overload may develop ->
- Congestive cardiac failure, pulmonary oedema, cardiac arrhythmia
what happen in refeeding syndrome
› ‘severe hypophosphataemia, sometimes accompanied by severe
hypokalaemia or hypomagnesaemia, of both; vitamin deficiencies
(particularly thiamine); fluid or glucose intolerance or both; and attendant
complications which may arise when malnourished patients are refed –
orally, enterally or parenterally’….
what might a person experience when refed after starvation
1› Changes in electrolyte balance, esp Mg2+, K+, PO4
3-
2› Vitamin deficiencies, esp B1
3› +/- Sodium/fluid retention
4› +/- Difficulty metabolising glucose
This may lead to major metabolic/physiological consequences, including
death
who is at risk of refeeding syndrome
› No/little food intake >5 days,
1- especially on a background of illness / malnutrition
2- BMI
how to reduce the risk of refeeding syndrome
1› Thiamin pre-feeding and for at least 3 days
2› Multivitamin
3› Feed slowly – start with small amounts even if hungry
4› Monitor electrolytes pre-feeding and daily
- Replete (K/Mg/PO4)as required and only increase intake if stable
- Monitor at least a week – signs of refeeding may not appear until a number of
days after commencing refeeding
5› Not huge intakes of either fluids or CHO until stable
what happen to james after administer to hospital
› Extremely low BP when admitted to hospital
› Provided parenteral thiamine
› Provided Vit K, multivitamin with trace elements daily
› Day 2 – 61kg (had been 80) – almost 20% body weight loss in 6 weeks!
› BGL 5.11mM, creatinine 0.1mM, Na 128mM, K 3.0mM; urine sample –
traces ketones
› 2l IVF and 1.5l oral fluid, with dextrose added after the first thiamine dose
› Presented with overt signs of Wernicke’s – may have been aggravated by
food provided shortly after found
› Presented with gaze palsy – resolved within 12h of admission (thiamin)
› Seen by psychiatrist – some paranoia noted (possibly the only sign of
Korsakoff’s)
› Day 3 – severe foot pain ?axonal peripheral neuropathy of B1 deficiency (Likely also
thermal effects)
› Day 4 creatinine level 0.06mM (renal function improving)
› Day 6 - tachycardia
› Day 10 – flown home to Brisbane
- Nystagmus, Mg 0.77mM (repleted)
› Day 16 – EEG – some abnormalities
› Day 23 – EEG – abnormalities resolved
› After 5 weeks – discharged – slight nystagmus persisted at least 5y later
give some reflection on the procedure perform on james after starvation
› Feeding before repletion may have exacerbated B1-deficiency symptoms
› Overaggressive rehydration may have caused mild heart failure
› No PO4
3- blood testing available in Nepal in 1992
What are current diet trends?
› Urine Therapy (urotherapy) diet › Paleo › Gluten free › Organic / ‘clean’ eating › Vegetarian › Vegan › ‘I quit sugar’ › VB6 (vegan before 6pm)/ Chegan (cheating vegan) › Clay Cleanse › South Beach, Blood Type, Sandra Cabot,…. › ……
Why do people follow these diets?
› Healthy
› ‘clean’ eating
› Weight management
› Fountain of youth
› ‘a magic bullet’
› Ethical reasons
› Religious reasons
› A friend of a friend’s sister told me
it worked for her….
› Doctor Google
› Traditional wisdom may appear to have let them down
› Marketed well
› Mystical
› beautiful
Fear mongering
- Eg butter vs margarine….. Margarine is evil
- Margarine was originally made to fatten turkeys but it killed them instead NO
- Eating butter increases absorption of micronutrients HUH?
- Margarine is high in trans fatty acids – DEPENDS
- Margarine is only one molecule away from plastic NO
- Butter is natural so it is better for you (arsenic is also natural!!)
what r the food supply change drivers at the primary production level
› Increased yields › Second crop / season › Drought resistance › ‘bug’ resistance › Physical properties (eg wheat – gluten) › Increased antioxidants › Altered macronutrient ratios › The next big thing! › Increased shelf life › More / less / altered distribution fat (eg beef) › Climate change › Scientific evidence eg p/u oils
Drivers of change for the food supply at the consumer level
› Perceptions of healthiness › Multiculturalism › Changes in kitchens / appliances › Advertising › ‘time poor’ / convenience › Increased shelf life – shop and pantry › Global village › Organic / locavore › Anti-animal cruelty / ethical › Masterchef, MKR, etc
Things to look out for consider a fad diet
› Whole food groups missing
› Supplements required
› Charismatic celebrity endorsement
› Promise of a quick fix
› Miracle ‘cure’ – if it sounds too good to be true, it is!
› Pseudo-science or a good dose of good science that is then taken off track
› Fear mongering
paleo diet fad diet
› 2013 – Google – most searched for weight loss method
› Picked up and championed by Pete Evans in Aus
› ‘caveman’ diet – akin to prior to agriculture / animal domestication
- What did a ‘caveman’ diet look like?
- 25% animal derived energy in Gwi people of Southern Africa
- 99% animal derived in an Alaskan population
› Claim we have been unable to adapt to changes in food supply….modern
food supply is the underlying reason for obesity, diabetes, cardiac disease,
… and those on paleolithic diet should therefore live longer and be more
healthy
› Avoid – grains, legumes, dairy, sugar, processed oils and foods, alcohol,
coffee
Paleo diet – for and against
Paleo diet – for and against
›
Gluten free diet
CAVEAT: strict GF diet essential for some…. those
with Coeliac disease – not a lifestyle choice!
There are also those with wheat allergy who must
strictly avoid wheat-containing foods, and those with
severe intolerance to gluten who need to limit gluten
to manage symptoms.
These are NOT the groups discussed in the next
slides
terminology
› Allergy – IgE immune modulated
› Intolerance – non-immune – NS involved
› Food aversion – often previous bad
experience / association; taste/texture aversion?
why go gluten free
› Coeliac Disease › Wheat allergy › Exercise-dependent, wheat-induced anaphylaxis › Gluten intolerance › You have been told it is good for you (NB below are NOT true) eg - gluten is indigestible - Not part of paleo diet - Causes autism - Improves athletic performance:
why people use gluten free diet
› Naturopath – many ailments – usually without proper testing
› Celebrities espousing the benefits eg Miranda Kerr, Gwynyth Paltrow,
Miley Cyrus,
what is low FODMAP diet
› Low FODMAP developed to manage symptoms of IBS not a weight loss plan › If you cut out the FODMAPs what else are you removing? Is the removal of other chemical components from the diet or the FODMAPs themselves assisting with symptom management? › This should also be a test diet, not a long term diet
driver of food supply change for Gluten free?
› Very difficult 20 years ago to find GF alternatives to staples such as
bread / pasta – alternatives often not palatable
› Driver of food supply change – high demand, whether by choice or
necessity:
- Supermarket alternatives – big business
- REALLY important for those with real health issues!!!!
- Coles / woolies have own GF ranges
- Usually MUCH more expensive than gluten-containing alternative
- BUT a huge range and many are either v similar to gluten-containing
alternatives or taste good in own right
- Health food stores
Problems with GF?
› Often low fibre
› ‘special dietary food’ therefore no mandatory fortification of flour with
folate, B1, I – many on GF diet are deficient
› Often highly refined, poor nutrient density, high GI
› Seen as healthy so more processed food eg biscuits may be consumed
› Ironically many Coeliacs would LOVE
normal bread!!! And compliance with GF
diet is often poor
Hallmarks of a fad diet (recap)
warning signs include
› Expensive to follow
- Ingredients may be expensive eg large amounts meat on paleo, making organic
produce a ‘must’,
- SUPPLEMENTS….. Usually marketed by the person promoting / designing the
diet
› Outlandish promises….. If it sounds too good to be true, it probably is!
› Whole food groups missing often eg grains and legumes – difficult to get
nutritional adequacy
› Usually elements of truth which make the diet appear plausible eg
decrease refined/processed foods or sugar and encourage otherwise
healthy lifestyle
› Usually promoted by charismatic people who make is sound like the
answer to all things healthy
Potential negative outcomes from fad diets
› A hole in the hip pocket! Might be the least of your worries
› Nutritional inadequacy – the results may not be seen in the short term, but
on a dairy free diet, what are the risks for osteoporosis / fractured bones,
(esp hip) in the future???
› Excess of undesirable nutrients eg saturated fat. ??? Long term risk for eg
cardiac disease?
› Eating disorder or at least disordered eating and a lifetime bad relationship
with food??
what determines the phenotype
epigenetic, environment and genotype
epigenetic is seen when the phenotypic variation persists even when genotype and environment are controlled for
what is epigenetics
Epigenetics: a system of gene regulation involving heritable changes in gene expression that occur independent of changes
to the DNA sequence
how is epigenetic gene regulation important for eukaryotic organisms
Epigenetic gene regulation is fundamental to the life of all eukaryotic organisms: it creates phenotypic variation not only within an individual, but also between individuals
what system is epigenetic and what P of epigenetic state
Epigenetic gene regulation is a binary system:
“On” or “Off”
Epigenetic states are probabilistic – every locus has some probability of being silent
how big is human genome and how it is packed
The human genome is ~3.1 x 109 bases long – over 2 metres worth in every human cell!
Eukaryotic DNA is packaged into chromatin.
is eucharomatin active or inactive
light stain, active
heterochromatin ?
silent, dark stain
what is chromatin
DNA+associated proteins and RNAs
how is chromatin structure and transcription rate determined
Nucleosome packaging determines chromatin structure and transcription state.
in active locus, there is molecule modification on histone protein tail
in silent locus, it is different modification that keep histone pack together. e.g methylation of CpG, inactive the gene
what does epigenetic modification allow in cells
Epigenetic modifications allow cells with precisely the same
genomes to adopt a multitude of phenotypes based on the activity of some loci and the silencing of others
Cell differentiation is epigenetic gene regulation par excellence
~25,000 genes in human genome – each cell type uses only a proportion, and the remainder are silent
how the cell’s epigenotype set during which period, what happen to the set epigenotype
A cell’s epigenotype – the pattern of active and silent loci – is set during differentiation
Once set, epigenotype is generally stable
is there a potential that error in epigenotype process maintained?
Errors in this process have the potential to be maintained for a lifetime, and sometimes even transmitted to future generations
Epigenetic state of many types of sequences needs to be precisely maintained – epigenetic machinery is constitutively active throughout the life cycle
t.telomere, centromere and telomere are heterochromatin
how is epigenetic interposed
Epigenetics is interposed between
genes and environment
Epigenetic modifications mediate genome function and are responsive to environmental cues e.g. cellular, organismal and external
The probability of epigenetic errors may be influenced by the environment and the most vulnerable time is during our development when cellular epigenotype is set
what is nucleosome
– the basic unit of chromatin
~146 bp of DNA wrapped in
1.65 left-handed turns around a histone octamer – same in all eukaryotic genomes
Histone octamer consists of two copies each of the core histones H2A, H2B, H3, and H4
Adjacent nucleosomes are joined by a stretch of free DNA termed “linker DNA” to which another linker histone (H1) binds
Post-translational histone modifications –
there is lots of possible combination, maybe a histone code?
give some example of histone modification
activation: acetylated H3K9
repression: methylated H3K9
activation: acetylated H3K14
repression: methylated H3K27
activation actylated H4 (K generally)
repression: sumoylation (K generally)
activation: methylated H3K4
repression: methylated H4 K2O
activation methylated H3K36
How do histone modifications alter
chromatin structure?
model 1: chromatin structural change (e.g. histone tail modification)
model 2: inhibit binding of negative-acting factor
model 3: recruit positive acting factor
DNA methylation
- Covalent modification of DNA itself
- Addition of a CH3 group to C5 on cytosine
- Does not alter Watson-Crick pairing, or the helical structure of the DNA
- Added by DNA methyltransferase, with the CH3 group donated by S- adenosyl methionine
- In mammals occurs primarily at cytosines in a 5’-CG-3’ context – “CpG methylation”
CpG methylation
• The idea that CpG methylation could represent a mechanism of cell memory arose independently in two labs in the mid 70’s
• CpG dinucleotide is self-complementary
– this led to the proposal that patterns of methylated/unmethylated CpGs could be copied when cells divide, providing a mechanism for mitotic inheritance of epigenetic patterns
CpG dinucleotides are under-represented in the
vertebrate genome
5-mC is more mutable than C (deaminates to U)
Most CpGs in the genome are methylated (>70%)
CpGs in constitutive heterochromatin CpGs in retrotransposons and their relics CpGs in introns and exons
Most intergenic DNA CpGs
CpG islands
• Originally detected in 1983 as the fraction of vertebrate DNA that was cleaved by the DNA methylation-sensitive restriction endonuclease HpaII
• When promoters started to be mapped it was noted many were in GC-rich regions. It is now known that ~65% of CpG islands mark gene promoters – about 60% of genes have CpG island promoters
• CpG islands often found at housekeeping genes – lack of methylation important in keeping genes active
• Definition now computational:
– GC content ≥50%
– length >200 bp
– Obs/Exp CpG > 0.6
CpG island methylation represses
transcription initiation
CpG methylation is not generally used for dynamic gene regulation –
it is a mark of permanent silence
(once you’re methylated you’re likely to be off for good!)
so what is methylated?
ACTIVE GENE PROMOTERS: no DNA methylation, H3K4me, H3K9Ac histone modifications
ACTIVE GENE BONEDY: yes DNA methylation, H3K36me histone modifications
SILENT GENE PROMOTERS-NORMAL CELLS: sometimes (~8%) DNA methylation, H3K27me histone modifications
SILENT GENE PROMOTERS-CANCER CELLS: often DNA methylation, H3K27me histone modification
OTHER SILEN SEQUENCES E.G. CENTROMERIC, RETROTRANSPOSON: yes DNA methylation, H3K9me histone modifications
Epigenetic silencing is a synergistic process
Epigenetic silencing involves a complex interplay between DNA methylation, histone mods, and chromatin proteins
If histone mods can be said to “close the door” on transcription, CpG methylation is they key that “locks” it
CpG island methylation is the most reliable marker of stable transcriptional silence
What distinguishes active from silent
chromatin?
in active chromatin (which is euchromatin): loosely packaged, replicates early, bound to TF and RNA polymerase, histone modifications: acetylated H3K9, methylated H3K4, methylated H3K36 (gene body), and no DNA methylation
in silent chromatin (heterochromatin)
- tightly packaged, replicate late, bound to heterochromatic protein like HP1, histone modification: methylated H3K(, methylated H3K27, there will be DNA promoter methylation
Where is epigenetics important?
• Gene regulation and cell differentiation
- X-chromosome inactivation
- Mobile element (retrotransposon) silencing
- Position-effect variegation
- Parental imprinting
X-inactivation in females
The Barr body – the inactive X-chromosome
X-inactivation in females
One of the two X chromosomes in therian females is silenced to ensure the correct dosages of genes on the X
Once silenced in early development, the inactive X is maintained through cell division – giving clonal patches of X-inactivation
Silencing is random …. Almost. In the placenta of eutherians and in all tissues of marsupials, the paternal X is always silenced.
Calico cats are only ever female – if you have
seen a male, he probably had XXY trisomy!
Mobile elements
Barbara McClintock discovered mobile genetic elements in maize (corn) in the 1940s. She recognised that mobile elements could silence (or sometimes activate) the loci they landed near, in a mosaic and heritable fashion – and called them “controlling elements”.
We now know that mobile genetic elements – transposons and retrotransposons – make up 50% of our own DNA!
Retrotransposons: sleeping monsters
Retrotransposons take up almost half our genomes - having amplified themselves via retrotransposition over eons
They are dangerous – their retrotransposition can cause insertional mutations
Hence …
They are MAINLY heterochromatic – in fact, DNA methylation may have evolved to keep them silent
They can control the expression of nearby genes – either by heterochromatising them, or by activating and causing transcriptional interference
Controlling elements – a model for epigenetic
phenomena that was ahead of its time
Controlling elements display behavioural features now recognised as characteristic of epigenetic phenomena:
- Mitotic heritability (stable throughout life)
- Meiotic heritability (stable between generations)
- Inter-individual variability
- Phenotypic mosaicism
REMEMBER for L6
- Epigenetics is the primary system of gene regulation in eukaryotes
- Epigenetic modifications change gene transcription state – active or silent
- Epigenetic modifications involve covalent changes to DNA and histones, and recruitment of silencing or activating proteins
- Epigenetic states can be modified by environment
Why are proteins so important ?
- Maintenance, repair, growth of tissues
- Formation of skin, hair, nails
- Production of plasma proteins
- Synthesis of antibodies, receptors, enzymes, hormones, neurotransmitters, channels & pores
- Milk protein in lactation
what s nitrogen balance
PROTEIN IN DIET–(digestion protein converted to a.a)-> a.a. metabolism in tissues -> urea synthesis for excretion
the amino acid metabolism in tissues —dynamic flow, constant turn over -> body protein
describe protein digestion
e.g. e.g. 100g of protein in diet, the trpsinogen secrete in pancreas get activated form trpsin in the gut, the protein is converted to peptides by trypsin, then peptide break down into a.a. the peptide can also converted in the gut epithelium into a.a. then a.a. (160 g) absorbed and transport via portal vein to liver. . liver convert the a.a. to urea, liver protein and plasma protein. in the fecal there is 10g of protein
there is 70g of endogenous protein.
L7
Protein Metabolism
After a meal containing protein:
– Portal blood ↑↑ amino acids
– Systemic blood smaller ↑ amino acids
– Liver regulates the fate of amino acids (50% -> urea or keto acids; 14% retained in liver; 6% secreted as plasma proteins; 23% secreted as free amino acids)
2 pathways for a.a metabolsim
amino acid-> keto acid->TCA cycle->CO2+H2O+energy
or
amino acid-> amino group-> urea-> urine
estimated daily turn over of protein in the whole body
body protein turnover go to
- muscle
- secreted gut protein
- protein synthesis and degradation
- white cell
- liver
- skin
what is a.a. pool
floating a.a. everywhere, last b/t meal not b/t days.
describe a.a.
a.a. different to each other due to side chain- the charge, size, 150 different a.a. we eat, only use 20 a.a.
different a.a. join together by peptide bond to form protein
what r essential a.a.
- Histidine (His) in children only
- Valine (Val)
- Leucine (Leu)
- Isoleucine (IIE)
- Lysine (Lys)
- Methionine (Met)
- Threonine (Thr)
- Phenylalanine (Phe)
- Trptophan (Trp)
what r the non-essential amino acid
- tyrosine
- glycine
- alanine
- cysteine
- serine
- aspartate
- asparagine
- glutamate
- glutamine
- argine
- proline
what is limiting amino acid
limiting amino acid= essential amino acid that is in low concentration such that it limites the rate of protein synthesis
what is nitrogen balance
Dietary intake N = loss of N from the body
B = I – (U + F + S)
= Intake - Losses
balance= N intake - ( urinary N+faecal N+skin,etc losses)
urinary N include urea ammonium and creatine
