Nutrition and starvation Flashcards
What are the major nutrients ?
- Fats
- Carbohydrates
- Proteins
What can carbohydrates and protein stimulate?
- Stimulate insulin secretion
What role does insulin have in muscle protein breakdown?
- inhibits muscle protein breakdown (MPB) to augment the anabolic effects of EAA on protein turnover
Explain the dynamic between muscle protein synthesis and muscle protein breakdown
- In healthy weight-bearing humans, muscle mass remains constant
- virtue of a dynamic equilibrium in protein turnover
Whata are glucose-dependent organs?
Brain, blood cells, renal medulla
- brain uses 50% of available glucose
- Preferential users of glucose :
- heart renal cortex (white skeletal muscle)
What organs use fatty acids as fuel?
Liver, red skeletal muscle
Protein/AA : NOT USED AS DUEL UNLESS EXCESSIVE INTAKE
Give a brief review of fed state
- Exogenous fuel utilisation
- Absorption of glucose and amino acids stimulates insulin secretion from pancreatic beta-cells
- Deposition of nutrients in tissue
- Glucose : glycogen, triglyceride synthesis
- Amino Acids : protein synthesis, mainly in skeletal muscle
What is protein-calorie malnutrition?
- Affects ~ 1 billion ppl ww
- US - 30-50% of patients will be malnourished at admission to the hospital
- 69% will have a decline in nutrition status during hospitlisation
- 25-30% will become malnourished during hospitalisation
What are consequences of malnutrition in hospitilised patients?
- Poor wound healing
- Higher rate of infections
- Greater length of stay
- Greater costs
- Increased morbidity and mortality
What is a fast?
-Exclusion of all food energy
What is starvation?
- Prolonged inadequate intake of protein and/or energy
What is Cachexia?
- Wasting induced by metabolic stress
- diseases e.g. cancer
What is a fasted postabsorptive state?
- Fed state ends when last nutrient is absorbed, body switches once again to endogenous fuel utilisatuon - constant cycling
- Decrease level of insulin, increase in glucagon
- Release, transfer and oxidation of fatty acids
- Release of glucose from liver glycogen
- Release of amino acids (stored as proteins) from muscle as a source of fuel
What is the progression of fasting?
- Normal post absorptive state : ~ 12 hours
- Release and oxidation of fatty acids from adipose tissue/ectopic stores
- Release of glucose from liver glycogen
- Liver glycogen capacity : approx 1000 kcal
- Equivalent to ~ 250 g carbohydrate/glucose
What happens when you fast longer than 24 hours?
- Further decrease in insulin, increase in glucagon
- Proteolysis and release of AA from muscle as a source of fuel
- Activation of hormone sensitive lipase
- Increase in lipolysis
- Increase in circulating FFA and tg
- Gluconeogenesis
What is gluconeogenesis?
Cori cycle in Liver- Muscle:
- glucose - converted to lactate/pyruvate in skeletal muscle (anaerobic) - travels back to liver for conversion to glucose
- Glucose- alanine (cahill cycle)
- AA deaminated in muscle
- C skeleton used for energy – pyruvate and NH2 – alanaine
- Alanine returns to liver for deamination
- NH2 - urea for excretion
- Pyruvate - glucose via GNG
Explain the glutamine cycle in the kidneys
- Muscle glutamine - kidney - glutamate + NH3- A-ketoglutarate – glucose
- Kidney is initially a minor source, increases to supply up to 50% of glucose over time
What is ketosis?
- Characterised by presence of ketone bodies (acetoacetate, acteonem b-hydroxybutyrate)
- Bi-products of fatty acid oxidation in liver
- Can be used by all tissues with mitochondria
- Utilized by brain, decreasing glucose consumption by 25%
- Can be prevented by providing 150 g glucose per day
What occurs when a fast is around 7-10 days?
-significant musce protein loss
10-12 g urinary N/day
- 360g LBM per day initally
- 1-2 kg LBM over first 7 days
- Lethal depletion after 3 weeks if no adaptation occurs - by the end of 2-3 weeks , decrease muscle protein catbolism
What occurs during long-term starvation?
- Decreased metabolic rate
- decreased actvity, body temp
- Conservation of protein
- decrease in muscle protein breakdown 64g to 30g / day
- Increased fatty acid oxidation
- Liver , heart and muscle use ketone bodies
- Decrease glucose availability
What happens to the brain during long term starvation?
- Decreased glucose availability
- Fed state uses 75%, completeluy oxidised
- 50% of glucose with ketones
- Decreased complete oxidation, recycles via GNG
In blood cells/ renal medulla
- Anaerobic glycolysis to pyruvate and lactate
What are some changes in organ function during starvation?
Liver : loss of mass
- Decreased protein synthesis
- Peri-portal fat accumulation (fattu liver)
- Hepatic insufficiency
- Skeletal muscle:
- catabolised for GNG - decreased mass
- utilisation of ketones : slower contractions
- Diminished function: intercostal muscles - decreased resp function
-imparied digestion
What can cause a decreased protein concentration?
1.) Reduction in protein synthesis
2.Increase in protein breakdown
3.Reduction in protein synthesis and increase in protein breakdwon
4.Increase in protein synthesis and even higher increase in protein breakdown
What can cause skeletal muscle atrophy?
- Immobilisation (Space flight, cast immobilisation, physical inactivity)
- Disease-related (cancer, HIV, rheumatoid arthritis, renal failure, burns,sepsis)
- Drug - related (glucocorticoids)
- Inadequate nutritional intake or digestion ( starvation, protein malnurtrition, impaired digestion )
- Ageing
Describe the process of muscle sarcomere degradation
- Calpins disassemble the sarcomere at the Z-line (by digesting Z-line proteins such as nebulin and fodrin), break it up into smaller pieced
- Myosin, actin and other proteins are then digested by the ATP-ubiquitin -dependent 26S proteasome which cannot digest connected proteins
- Some proteins are also degraded by cathepsins, which are located in lysosomes.
What does insulin supress?
- Inhibits muscle protein breakdown to augment the anabolic effects of EAA on protein turnover
What is the effect on nutrition on Muscle Protein Turnover?
- In healthy weight-bearing humans, muscle mass remains constant by virtue of a dynamic equillibrium in protein turnover
- MPB> MPS [fasted], MPS>MPB [fed]
Compare starvation in a lean and obese individual
- Lean 70kg man (13% fat) survival ~ 64 days at 1500 kcal/day
- Obese - 242-302 at 2000-2500 kcal/day
What is gene regulation during starvation?
- Decrease in totala RNA (decrease in ribosome content)
- Ubiquitin-proteasome mRNA increases : greater capacity for muscle protein breakdown
- Carbohydrate- catabolism enzymes decrease but no upregulation of fat metabolism enzymes : Preservation of the limited glycogen reserves
- Myosin heavy chain anf collagen expression goes down
- Apoptosis markers increase
- 4E-BP1 Increases : Increased inhibition of translation
What are some key factors in regulating muscle atrophy?
- E3 ubiquitin ligases such as MADbx and Murf1
- determine the protein breakdown rare and net protein changes
- measured with RT-PCR to confirm microarray
What is cathepsin L?
- protease
- located in lysosomes
- mRNA and protein induced in muscle wasting conditions (Sepsis, cancer, dexamethasone treatment)
- Induced by dexamethasone ( synthetic glucocorticoid that induces muscle atrophy)
- CL mRNA increases in response to unloading
