The Fasting State

Nutrition

The Fasting State

Energy and ATP:
Fuels are oxidized to generate ATP.
ATP releases energy that is used to drive body processes
Some energy released from ATP is lost as heat.
Intake of food does not meet the minute to minute needs for ATP and so body needs energy stores.
Meals can meet body’s need for energy for period of hrs, blood can meet the body’s need for energy for the period of minutes and ATP for seconds. However, energy stores can provide energy for periods of months.
In general teenagers require more energy b/c growing requires additional energy.
Old people require less energy b/c their REE goes down.
Components of Energy Expenditures:
Resting Energy Expenditure (REE):

Energy required for maintenance of vital processes
Main determinant of REE  Lean body mass
Technique of measurement  indirect calorimetry, to assess O2 consumption.
Estimation equations e.g. Harris-Benedict Equation
Energy from main classes of fuel:

Carbos  4 kcal/g

Fat  9 kcal/g

Protein  4 kcal/g

Alcohol  7 kcal/g

1 kcal  4.18 kj

Thermic Effect of Food (TEF):
Energy required for digestion, transportation and metabolizing the nutrients in the meal and also anabolism
Goes up for few hrs following meals.
Thermic Effect of Exercise (TEE):

Energy required for muscular exercise
Highly variable
Adaptations (Adaptive thermogenesis, AT):

Chronic low energy  adaptation in the energy expenditure  energy expenditure goes down  survival response
Fat stores the most energy and releases the most energy so fat is used to supply the body w/ energy b/w the meals. (Protein sparing)
Carbos can provide energy for 1 day
TAGs can provide energy for 111 days
Proteins can provide energy for 18 days
Muscle stores water along with energy (in the form of glycogen) and adepocyte stores energy in the form of TAGs w/o water and so adepocyte is 10X caloric dense than muscle.

Fuel Fluxes:
Consumer organs:

Brain will use ketoacids if available as their first choice for energy, but ketoacids are not usually available so most of the time they use glucose as the source of energy. It doesn’t use fatty acids as the source of energy.
Muscle uses fatty acid as the source of the energy but if FAs are not present they the next choice is ketoacids and only when both of the FAs and ketoacids are not present it would use glucose.
Maintainer Organs:

Maintain supplies to consumer organs either by releasing their own stored fuels or from other organs.
Kidney can produce and release glucose in chronic acidosis conditions.
Liver:

Uses AAs during meals to generate ATP
Uses FAs b/w meals to generate ATP
Stores carbos as glycogen and small amounts of TAGs
Converts glycogen and AAs to glucose
Converts FAs to ketoacids to supply FAs for liver (?)
Adipose Tissue:

Uses glucose during meals to generate ATP
Uses FAs b/w meals to generate ATP
Stores energy as TAGs
Converts TAGs to FAs to supply liver w/ FAs
Prolonged Fasted State Adaptation:

The key to adaptation is the production of sufficient keton bodies form free fatty acids in the liver, to displace the brain’s need for glucose. Once the glycogen supplies are depleted, gluconeogenensis from protein is the only source of glucose for the brain and that would deplete body protein rapidly.
Glucose and Insulin levels go down and then stabilizes at lower levers which is required for the metabolic adaptation.
Glucagon levels are only of importance in controlling hepatic glucose production and doesn’t change.
Free FA mobilization and plasma levers of FFAs increases  get converted to keton bodies by liver  increased keton bodies in blood and urine  body protein conservation and mild ketoacidosis.
Levels of urea nitrogen shows catabolism of protein by liver and levels of ammonia nitrogen shows catabolism of protein by kidney and as the fasting time goes up the levels of urea nitrogen goes down and ammonia nitrogen goes up.

The Fed State

General:
Any excess energy over REE, TEE and exercise is stored as fat once glycogen stores are replete.
Insulin is major fed state anabolic hormone.
High insulin is not absolute necessity for anabolism to take place. It depends upon what energy substrates are provided.
The Intermittently Fed State:
Although breakfast is the smallest meal the glycemic rise is higher and longer than that following lunch and supper. Insulin follows the glucose response.
Over night insulin levels go really low to maintain plasma glucose levels so in the morning when food is introduced, body has to adjust to the incoming food the most and so glucose and insulin rise the most when c/w other meals of the day.
At night lypolysis goes up b/c insulin levels are low at night. Since insulin is the potent suppressor of lyposysis in the morning/during the day when insulin levels goes up lypolysis goes down and so FFAs levels stay low thought out the day.
Fuel Homeostasis in Uncontrolled Diabetes:
Diabetes represents the inability to efficiently respond to the fed state.
If insulin is the main fed-state “anabolic” signal, and the individual either cannot secret it or secretes it late and in insufficient amounts to overcome tissue insulin resistance, then homeostasis is disrupted  Superfasted state – exogenous and endogenous fuels are secreted at the same time in to the circulation and their clearance is impaired.
Fuel Homeostasis in Hypoenergetic State:
Very low energy all protein diet for obesity  low insulin, low glucose, high FFAs and keton bodies – Protein loss is prevented here by providing about 1 g/kg/ day of protein (protein sparing)
Circulating protein stimulates less insulin secretion than carbohydrates  Low insulin  Lypolysis  ketogenesis
Fat can be added as a source of dietary energy in the cases of refractory childhood epilepsy.
Fuel Homeostasis in Continuous Parenteral Feeding:
Isocaloric (Isoenergetic):
Continuous IV feeding providing constant amount of protein (1 g/kg/day), full calories at 40 kcal/kg/day.
Energy can be provided in three different mixtures: N balance - same in all 3 cases
Only as Glucose: Higher insulin, Higher glucagons, Higher lactate
Only as Lipid: Higher FFA, Higher ketones
½ Glucose + ½ Lipid
Hypoenergetic (Hypocaloric):
w/o full calories, protein sparing
When person is ill for shorter periods e.g. postoperative period
3 different types:
Glucose alone w/o Protein: (-)ve N balance
P1 – Small amount of protein, + glucose or + lipid: Improvement in N balance
P2 – Much higher amount of Protein: N equilibrium
4 Things to be learned:
Exogenous protein spares protein vs. glucose alone
Dose response: more protein sparing w/ more protein provided
In short interval (only 3 days) hypocaloric feeding gives no extra benefit over P1 alone
Mix of substrate determines production of anabolism
N balance:
Better N balance w/ higher protein inputs w/o increasing energy inputs
At any protein intake, adding extra energy improves N balance
Improvement in N balance is seen after input has been maintained for many days b/c adaptations occur w/ time.

Nutrition & the Kidney

Effects of Nutrition on the Normal Kidney:
3 Primary Fx of Kidney:
Excretion: involves water, minerals and organic compounds
Endocrine: 1,25-dihydroxycholecalciferol and erythropoeitin
Metabolic
Kidney also excretes or degrades other hormones that is influenced by nutrients like insulin
Kidneys are required to respond to major changes in intake of water, sodium, potassium, acids and bases, calcium and phosphorus, magnesium and trace elements in order to maintain homeostasis.
Protein Effects:

Increase in renal blood flow starting 2 hrs after a protein meal and lasting about 1 hr
RBF and GFR also increases following IV AA infusion
These effects are seen b/c of glucagons, GH and Insulin like Growth Factor I.
Malnutrition Effects:

Transient or permanent
Decreased protein intakes  Decreased RBF and GFR
Low protein diet  Decreased urea production Decreased plasma urea filtration Decreased medullary hypertonicity  Impaired capacity to concentrate urine (capacity to dilute urine is not affected)
Decreased capacity to acidify the urine/Impaired excretion of an acid load b/c of insufficient phosphate intake and that leads to renal conservation of H2PO4 and so less availability of H2PO4 for excretion. Also, synthesis and excretion of ammonia also goes down in malnutrition.

Effects of Nutrients on the Progression of Renal Insufficiency:
Loss of functioning nephrones to the point of mild renal insufficiency  adaptation in remaining nephrones like increased Glomerular plasma flow and GFR, nephorne hypertrophy  alteration in chemical, electrical and pore size barriers  increased gradient across the Glomerular capillaries  injury to remaining nephrones  Progression of renal failure.
Nutrients that contribute to the progression of renal failure:

Protein:
High protein increases pressure and flow  damage to Glomerular BM  permeability to large molecules  deposition in mesangium mesangial expension  inflammation  scarring
Low protein intake can prevent these changes
Low protein intake is advised in mil to moderate renal failure
Phosphorous & Calcium:
Low phosphorous intake  decreases the deposition of calcium phosphate in kidney tissue  prevents progression of renal failure
Low protein diet are usually low in phosphorous too

Causes of Progressive Renal Failure:

Continued activity of the underlying renal failure
Systemic hypertension
High protein diet
High phosphorous diet
Vitamin D overdose: causes hypercalcemia
Hyperuricemia
Acidemia
Mechanisms of Progressive Renal Failure:

Intraglomerular capillary pressure and capillary blood flow
Intraglomerular transcapillary hydraulic pressure
Glomerular hypertrophy
Calcium phosphate or calcium oxalate deposition in kidney
Urate deposition in kidney

Nutritional and Metabolic Consequences of Chronic Renal Failure:
Clinical changes seen in CRF:

Weakness
Feeling of ill health
Insomnia
Fatigue
Anorexia
N/V
Diarrhea
Itching
Muscle cramps
Hiccups
Twitching of extremities
Tremors
Irritability
Decreased mentation
Inability to excrete fluid and electrolyte loads  CHF and Hypertension
Altered electrolyte concentrations  arrhythmias, seizures, metabolic acidosis
Dietary therapy and dialysis are helpful
Consequences of CRF:

Accumulation of products of protein and AA metabolism – urea, creatinine etc
Inability to excrete salt loads
Impaired ability to excrete water, K, Ca, Mg, PO4, SO4, H+
Impaired intestinal absorption of Ca
High risk of vitamin deficiencies: B6, C, folic acid, 1,25-dihdroxyD
Retention of toxic chemicals like Al
Increased secretion of some hormones like insulin
Decreased secretion of erythropoietin and 1,25-dihydroxyD
Resistance to insulin
Increased sensitization to glucagons
Impaired renal metabolism of glutamine, alanine and glycine
Accumulation of metabolic end products like urea, creatinine etc
Hyperparathyroidism as consequence of low 1,25-dihydroxyD, ass w/ osteodystrophy
Hyperlipidemia
Accelerated CVD
Wasting syndrome w/ loss of muscle, fat and multiple functional consequences of these

Dietary Management of CRF:
Goals of diet therapy:

Stop the rate of progression of renal failure
Maintain good nutritional status
Prevent or minimize those aspect of uremic toxicity that may be influenced by diet (like eating food containing of purins ??)
Moderate the metabolic derangements as much as possible
Management:

Monitoring the diet and change w/ worsening renal function
Major changes are required when dialysis is begun
Recommended nutrient intakes for nondialyzed patients w/ CRF and for patients undergoing maintenance hemodialysis or chronic peritoneal dialysis:

Protein:
Recommended protein intake for normal adult person is 0.8 g/kg/day
Protein intake should be restricted in person w/ CRF
However, if the person is on dialysis then don’t have to restrict protein that much b/c dialysis can remove undesirable end products of protein and AA metabolism.
In DM, the efficiency of body protein metabolism is impaired and there may be risk to restriction
Energy:
W/ low protein intake, the body protein metabolism is compromised if energy intake is less than requirements especially when insulin is insufficient or its action is decreased as in renal insufficiency.
Lipids:
Renal insufficiency  high incidence of hyperlipidemia  elevated TAG, LDL, VLDL and low HDL  atherogenic
Recommended to take 30% of calories as fat w/ < 10% as saturated fat and < 300 mg/d of cholesterol
Phosphorous and Calcium:
Low diet phosphorous recommended in CRF and phosphate binder (calcium or aluminum salts) can be used also
Dairy products have high phosphorous
Magnesium:
Mg levels increase w/ renal failure so intake of Mg should be restricted
Pt should avoid Mg containing antacids and laxatives
Sodium and Water:
Decreased ability to excrete sodium and water
Diuretics can be used
Restriction in Na intake
Potassium:
K retention is almost the rule in renal failure and so it’s intake must be very strictly restricted
(“40-40-40” diet for severe renal failure: 40 g protein, 40 meq Na and 40 meq K)
Vitamins:
Mild-moderate risk of deficiency of water soluble vitamins b/c decreased intake (of water ?) , altered metabolism and use of a number of medications that may interfere w/ absorption, metabolism an action of certain of them. Most likely to be deficient are B6, C and folic acid and should be prescribed prophylactically
Vit A is elevated in uremia and so it should not be given (risk of bone toxicity if high)
Vit K should be given if antibiotics are to be administered
Vit E doesn’t have to be supplemented
Vit D can be given if needed w/ Ca levels monitored
Acidosis:
Alkali supplements when blood pH is < 7.35 or serum bicarbonate is < 20 meq/l
Calcium carbonate is an alkali supplement that can be given - advantage: will lower phosphorus levels
Sodium carbonate is another alkali supplement and can be given as long as can handle Na levels

Dietary Management of Acute Renal Failure:
The most common causes:

Shock
Severe infection
Trauma
Medications
Obstruction
GN
Patients will have fluid and electrolyte disorders, acid-base disturbances, uremic toxicity and will develop very rapid tissue wasting
Nutrients will be provided parenterally at the start of the tx

Nutrition Alterations in Renal Stone Diseases:
A high urine volume is desirable – achieved by increasing fluid intake
In the cases of those types of stones that are more soluble in alkaline urine, oral alkalization supplements are given
In the presence of intestinal disorders such as the short bowel syndrome that predisposes to oxalate hyperabsorption, high oxalate containing foods are to be avoided. If there is high oxalate then high Ca should be given, which will lower the hyperabsorption of oxalate
Uric acid stones: Alkaline urine, avoid alcohol, avoid food w/ high purine
Calcium Nephrolitiasis ass w/ decreased citrate excretion in distal RTA – sodium or potassium citrate supplementation can be used
W/ cystinuria and cystine stones the dietary interventions are to increase urine volume and alkalize the urine.

Nutrition & Cardiovascular Disease:

Background:
Number of LDL particles is reflected by the levels of apoprotein B, b/c LDL particles have a relatively fixed number of apoprotien B. Therefore the level of apoprotein B is a strong predictor of coronary heart disease b/c it reflects LDL level.
The uptake of LDL particles by macrophages is not receptor dependent.
Definition / Prevalence of Hypercholestrolemia:
Total serum cholesterol of 5.2 mmol/L (200 mg/dl) or less is considered desirable.
Total Cholesterol of 6.2 mmol/L (240 mg/dl) or more is considered to be elevated.
Total cholesterol levels b/w 5.2 and 6.2 mmol/L are borderline
Serum cholesterol are considered to be elevated in pt w/ 2 or > risk factors.
Risk factors for Coronary Artery Disease:
Modifiable:

-Smoking

-Hypercholesterolemia

-Low HDL cholesterol

-Hypertension

-DM

-Obesity

Non Modifiable:

-Age

-Family Hx of premature coronary artery disease

-MI or sudden death in 1st degree relative < 55 yr of age

Friedewald Equation:
LDL Cholesterol = [total cholesterol] – [HDL cholesterol] – [TAG]/5
The decision to Tx hyperlipidemia should be made on at least 2 measurements in the fasting state, taken 2-3 months apart. The decision to use drug therapy should be based on hither LDL cholesterol values that stay high despite 6 months of diet therapy.

Dietary Therapy initiation Levels / Drug Therapy Consideration Levels / LDL Goal
W/O CHD and w/ < 2 RF / 160 mg/dL / 190 mg/dL / <160 mg/dL
W/O CHD and w/ 2 or > RF / 130 mg/dL / 160 mg/dL / <130 mg/dL
W/ CHD / > 100 mg/dL / 130mg/dL / </= 100 mg/dL

Diet Components:
Dietary Cholesterol:

Cholesterol is found as integral component of cell membrane of all animals, birds and fish but is absent in plants, nuts and seeds.
Saturated fat diet  high LDL
High dietary cholesterol  high circulation cholesterol
Fatty Acids:

All saturated fatty acids are not as potent.
Saturated fatty acids can be found in red meat, whole milk products and plant sources like coconut and palm oils, cocoa butter and hydrogenated vegetable oils (Hydrogenation make unsaturated FAs  Saturated FAs.
Monosaturated FAs (oleic acid) are considered good to replace saturated FAs b/c they lower LDL a little and don’t decrease HDL levels.
Polyunasaturated FAs are divided into two groups:

-Omega 6 = Linoleic acid: found in vegetable oil  decreases LDL and may decrease HDL

-Omega 3 = Linolenic acid: Found in fatty fish and shellfish  Lowers TAGs, VLDL and apoprotein B production

AE: Contamination w/ mercury or pesticide, excessive bleeding and fat-soluble vitamin toxicity

Dietary trans-FAs  atherogenesis: Found in animal fats and hydrogenated vegetable oils
Plasma Homocysteine:
Cardiovascular Disease RF
Atherosclerosis and thromboembolism seen in people w/ high homocystine levels
Homocystine levels increase w/ age, male, smoking and some medications.
Homocystine levels can be lowered w/ Vitamins B6, B12 and folate.
Fibers:

Non digestible carbohydrates from the cell walls of plant foods
Insoluble fibers are useful in constipation but have no effect on hyperlipidemia
Soluble fibers (gum, pectins and mucilages) have antihyperlipidemic effect

-Sources: citrus fruits, barley, oats, dry beans and peas

-AE: Eructation, abdominal bloating and flatus

-MOA: similar to bile acid binding resins

Alcohol:

Raises A-I and A-II and HDL3
Controversy about use of moderate alcohol for protection against coronary heart disease
Carbohydrates:

Carbohydrates like vegetables, fruits and grains should be used to replace saturated FAs
Natural foods are high in complex carbohydrates and are usually low in caloric density and contain a variety of vitamins and minerals.
The indication for medication is based on LDL and not on cholesterol

Diet Prescription:
The dietary management of hypercholesterolemia is based on 3 major components:

Restoration of normal body weight
Reduction of intake of saturated fatty acids and dietary cholesterol
Increase in fiber intake
Two steps of the dietary changes:

A reduction of the major and obvious sources of saturated FAs and cholesterol in the diet (can be prescribed by physician)
Careful attention to whole diet  to reduce the intake of saturated FAs and cholesterol to a minimal levels compatible w/ an acceptable and nutritious diet (requires help of a dietician)

- Replacement of saturated FAs w/ carbohydrates and polysaturated FAs