Metabolism And Temperature Regulation Flashcards
Classes of nutrients
Carbohydrates
Proteins
Fats
Water
Vitamins
Minerals
BMI formula
Weight (kg) / height (m) ^2
Normal bmi
Obese and severely obese?
20 - 24
>30 obese
>40 severely obese
Average male calorie intake
BMR 2000 kcal/day
+500-2500 kcal more depending on activities
Balanced diet percentages of nutrients for energy
55% carbs
15% protein
30% fat
What is the role of salivary amylase
Breakdown of complex carbohydrates producing oligosaccerides
Enzymes in intestine that brake oligosaccharides down to hexoses?
Maltase, lactase, sucrase
Daily requirement of carbs for an adult
5-10g/kg
Classifications of proteins in diet
Class I - contain all essential amino acids
Class II - lacking one or more essential amino acid
Enzymes that break down proteins
Pepsin
Trypsin
Chemotrypsin
Peptidases (for short peptides)
Average daily requirement of proteins for an adult
For a neonate
0.5-1g/kg
5g/kg
What occurs to surpluses amino acids in the body
Excreted in urine
What is a triglyceride
Three fatty acids and a glycerol
Types of dietary lipids
Triglycerides
Cholesterol
Phospholipids
How are triglycerides absorbed in the intestine
How are they transported
Simple diffusion post breakdown to free fatty acids by lipase or as micelles
Reformed in cell to form triglycerides then transported with phospholipids, cholesterol and carrier proteins as chylomicrons
Average intake of fat in diet
1-2g/kg
Examples of essential fatty acids
Linoleic
Linolenic
Arachidonic acids
What are vitamins
Organic molecules essential to life but which cannot be synthesised
Water soluble vitamins
B and C
Fat soluble vitamins
A,D,E,K
What is needed for lipid soluble vitamin absorbtion
Bile and pancreatic lilase
What proportion of energy from catabolism is available for work? What happens to rest
40%
Rest lost as heat
What are subcatagories of energy expenditure
External work (eg muscles)
Internal work (eg cardiac contraction or cellular processes)
Energy stored
What is basal metabolic rate
Total energy expanded over 24 hours by a subject under standard conditions at mental and physical rest in comfortable environmental temperature and fasted for 12 hours
What influences basal metabolic rate?
Age (increases in childhood, decreases in elderly)
Sex (higher in men)
Height, weight and BSA (core body temp better maintained in obesity thus lower bmr)
Pregnancy, menstruation and lactation
Hormones (eg thyroxine, adrenaline)
Conscious level
Temp
Eating
Emotional state
Activity
Presence of sepsis or disease
Malnutrition
Effect of emotional state on basal metabolic rate
Anxiety raises
Depression lowers
Effect of eating on Metabolic rate
Increases post injestion of food
What increase in BMR is seen with an increase of 1oC body temp?
10%
Basal metabolic rate in average young male in kcal and watts
2000kcal/24o
96watts/24hrs
Effect of thiamine deficiency
Beri beri and heart failure
Effect of flavine deficiency
Angular stomatitis
Effect of niacin deficiency
Pellagra dermatosis, mental disorders
Effect of folate deficiency
Macrocytic anaemia, stomatitis, diarrhoea
Result of cyanocobalamin deficiency
Macrocytic anaemia, optic neuritis
Effect of Vit a deficiency
Night blindness
Effect of Vit d deficiency
Rickets, osteomalacia
Effect of Vit e deficiency
Anaemia
Effect of zinc deficiency
Growth restriction
Hypogonadism.
How can BMR be meauresed
Whole body calorimeter
Place in chamber and measure temperature rise in a steady flow of water passed through the chamber.
How can BMR be estimated
Measuring oxygen consumption
Oxygen consuption per hour multiplied by 4.8kcal of heat produced per litre oxygen consumed
What is the respiratory quotient
What principle does it use
Dimensionless number used in calculation of BMR
Ratio at steady state of co2 expired to o2 consumed
That the amount of energy released from food is proportional to o2 used
What are the respiratory quotient for food groups
Glucose 1
Fat 0.7
Protein 0.8-0.9
Ethyl alcohol 0.66
What can cause issues with RQ calculations
Co2 expired can vary with non metabolic states eg hyperventilation in anxiety
What is metabolism
Biochemical reactions with brakdown, synthesis, and dextoxification
What weight of atp does an adult at rest use every day
40kg (by continued recycling)
What is NADH
How does it carry energy
Nicotinamide adenine dinucleotide
Carries donated electron
Other than atp what other energy I carrying moleculese does the body use
NADH
Nadph
Coenzyme A
Creatine phosphate
Thiamine pyrophoshate
Flavine adenine dinucleatide (fadh2)
Mechanisms of metabolic control
Substrate availability - control of transport of substrate into cells (e.g insulin promoting glucose entry into cell)
Allosteric enzyme control - binding of modulator away from active site (eg 2.3-DPG)
Hormonal control - wide ranging hormones create wideranging systemic effects
What stimulates insulin secretion
Glucose and amino acid uptake
Parasympathetic innervation
Actions of insulin
Glucose uptake to cells
Hepatic glycogen synthesis
Inhibition of gluconeogenesis
Stimulation of fatty acid precursor formation
Increased uptake of branched amino acid from gut
Stimulates protein formation
What is Co-secreted with insulin?
What does it do
Amylin
Promotes lactate transfer back to liver and generation of fat stores.
Stimulation for glucagon secretion
Hypoglycaemia
Actions of glucagon
Inhibits glycogen synthesis
Stimulates glycogen breakdown and gluconeogenesis
Activates lipases in adipose tissue
Actions of adrenaline and NA on glucose
Promote glycogenolysis especially in muscles
Mobilise fatty acids.
Sources of glucose in the body
Dietary intake
Breakdown of complex carbs
Synthesis from precursors
Net gain of moles of atp from metabolism of one mole glucose under aerobic conditions
Energy from this
38 moles
288kcal per mole of glucose
What accessory carbohydrate pathway is there
Pentose phosphate pathway (Hexose monophosphate shunt)
What is glycolysis. What are the number of carbon atoms in starting and finishing molecules
Net gain of energy carriers
Breakdown of glucose (C6) to pyruvate (C3)
Net gain 2 ATP, 2 NADH,
How is 2.3 DPG produced, how does it work to produce right shift of the ODC
What is the concentration of 2.3 DPG in stored blood
Produced from 1.3 DPG (a step in glycolysis)
Binds allosterically between the two beta chains of Hb reducing affinity for oxygen
In stored blood there is low concentrations, thus can be hard to offload o2
Body reserve weight of glycogen
Where is it found
325g
3/4 in muscle
1/4 in liver
How is glucoses added to glycogen?
How is it separated
Added by phosphorylation and branching enzyme to create new branches
Phosphorylase enzyme and de branching enzyme to remove branches
How can muscle mass be converted into usable energy
Where does this occurs
De-amination of amino acids into pyruvate and lactate then conversion of these to glucose by gluconeogenesis via oxaloacetate intermediatery
Liver, some in renal cortex
What is the pentose phosphate pathway?
Where is it important
Conversion of glucose-6-phosphate into ribose-5-phosphate, co2 and nadph
Important where reductive power of nadph is needed such as cell memebrane repair, amino acid synthesis, steroid synthesis, fatty acid synthesis and production of nucleus acids (found in liver, fat, erythrocytes and testes)
What happens to pyruvate before entering citric acid cycle
Oxidation to acetyl-coA creating one NADH and co2
What are the feeds into the citric acid cycle?
Carbs and lipids feed in via acetylCoA
Protein feeds in via oxaloacetate, alpha ketogultarate and fumarate
Energy production of the citric acid cycle
Three NADH
One gtp
One fadh2
Brief overview of oxidative phosphorylation
Atp generation using the high potential electrons in NADH and fadh2 passed down through carrier proteins on inner mitochondrial membrane
Transfer of electron from carrier to protein activates proton pump pumping H+ out, creating a H+ gradient
As h+ flows back in through atp synthase generates ATP
What is von gierkes disease
Effect
Glucokinase deficiency
Large liver and kidneys, stunted growth, lactic acidosis, dolls face
What groups are found on an amino acid carbon atom?
Amine, carboxyl, hydrogen atom, R group.
Uses of amino acid pool
Protein production
Purines and pyramidines
Hormones
Neurotransmitters
Creatine
Gluconeogenesis
Fatty acid synthesis
Citric acid cycle
How are amino acids broken down
Amino group removed and excreted as urea
Residue enters other pathways (eg citric acid cycle)
What is transamination
Transfer of amino (nh2) group to another molecule
What is demaination
Removal of amino group leaving a carbon skeleton that can be metabolised
eg. Serine to pyruvate and nh4
How is balance of amino acids considered?
What results in pos or neg balance
Nitrogen balance
Positive - growth, anabolic steroids, convalescence, decreased excretion (eg renal failure)
Negative hypermetabolic state (starvation, sepsis), burns,
How is nh4+ removed
Kidneys - converted to nh3 and h and excreted in urine
Liver - converted to carbamyl phosphate contributing to urea formation
What supplies the energy for first few seconds of muscle contraction
Atp generated from Creatine
What is creatinine
Anhydride of creatine formed as a metabolite for excretion in urine
Functions of purines and pyramidines
Dna and rna
Energy store (atp gtp etc)
Cofactors
Structure of a purine
Examples
Metabolism
Double ring - 6 and 5 membered nitrogenated ring
Adenine, guanine
Metabolised to uric acid
Structure of a pyramidine
Examples
Metabolism
Single six membered nitrogenated ring
Cytosine, thymine, uracil
Broken down in liver
Types of lipids in the body
Fatty acids
Triglycerides
Plasma lipoproteins
Phospholipids and glycolipids
Cholesterol
How are lipids transported in plasma
Lipoproteins 95%
Free fatty acids 5%
Energy gained from metabolism of fatty acid oxydation
9kcal/g
Why are fatty acids by weight of tissue so much more energy rich than glycogen
More energy per g of fatty acids
Hydrophobic so anhydrous thus no wasted weight with water
What is the process of fatty acid breakdown?
Where does it occur
Beta oxidation
In mitochondria matrix
Process of beta oxidation of fatty acid
Combined with acetyl CoA in cytoplasm
Carried on carrier protein carnitine into mitochondria
Dissociates from carnitine which then returns to cytoplasm (carnitine shuttle)
C2 fragments then broken off fatty acid producing acetly CoA
Where does fatty acid synthesis occur
Cytoplasm
How does fatty acid synthesis occur
Adding successive acetyl CoA molecules transferred out of mitochondria on citrate carriers
Citrate dissociates in cytoplasm converted to pyruvate which is transported back into mitochondira to reform citrate
Acetyl CoA molecules joined by reducing power of nadph
Function of cholesterol
In cell membranes produces fluidity
Precursor to steroid hormones
How do cells obtain cholesterol
From LDL
What does HDL do
Removes cholesterol from dying cells and membranes for recycling
Main function of ldl
Delivery Of cholesterol to cells
Main function of vldl
Carries excess triglycerides from liver
Function of chylomicrons
Carries dietary lipids to tissues for metabolism
What are the eicosanoids
Derivation?
Examples
C20 unsaturated fatty acids with a five carbon ring
Derived from arachidonic acid
Examples - prostaglandins, leukotriens, thromboxanes, prostacyclin
What is arachidonic acid formed from
Linoleic acid
Characteristics of eicosanoid effects
Highly localised
Short lived
What are the ketone bodies?
When are they formed?
Acetoacetate and gamma hydroxybuteyric acid
When excess acetyl CoA is present diverted to form ketones
When uncontrolled diabetes or starvation acetyl CoA formed from fatty acids. When insulin very low, increased glucagon levels (stimulating beta oxidation) or decreased oxaloacetate due to high gluconeogenesis then acetyl CoA can become excessive.
What proportion of glucose does the brain utilise at rest? What accounts for most of the rest?
Brain 70-80%
Erythrocytes most if the rest
What do resting muscles use for metabolism
Fatty acids
What occurs over first 12-24 hours of starvation
Glycogen increases triggering glycogenolysis to maintain glucose for the brain
Glycogen reserves then become depleted in 12-24 hrs and blood glucose falls to subnormal levels.
Noradrenaline, cortisol, growth hormone, thyroxine and oestrogen then increase.
What happens 24hrs to 4 days of starvation
Gluconeogenesis increases with breakdown of muscle proteins and lipolysis
Acetyl CoA accumulates leading to ketone formation
What happens after 4 days of starvation
As ketones increase then protein metabolism decreases - does slowly continue to break down however to provide glucose for certain tissues such as erythrocytes and some of CNS.
Half of the brains energy now derived from ketones
Once fat stores depleted death follows as result of protein malnutrition
How does exercise cause glucose to enter muscle cells
How else are muscle cell energy requirements met?
Glut4 - insulin independent (expression stimulated by insulin and exercise)
Glycogenolysis in the muscle
Gluconeogenesis as exercise prolongs
Effects of insulin in starvation
Decreased gluconeogenesis, glycogenolysis, proteins breakdown and lipolysis.
Increased peripheral glucose utilisation
Effect of glucagon in starvation
Increases gluconeogenesis, glycogenolysis, protein breakdown, lipolysis, and peripheral glucose utilisation
What hormones does glucagon stimulate the release of
Insulin
Growth hormone
Somatostatin
Effect of cortisol during starvation
Increased gluconeogenesis
Decreased glycogenolysis
Increased protein breakdown
Increased lipolysis
Decreased peripheral glucose utilisation
Effect of catecholamines during starvation
Increase hepatic gluconeogenesis, increased glycogenolysis, increased lipolysis, decreased peripheral glucose utilisation
Effects of growth hormone in starvation
Increased hepatic glycogenolysis
Decreased protein breakdown
Increased lipolysis s
Effect of progesterone and oestrogen during starvation ( and clinical squale commonly seen)
Decreased peripheral glucose utilisation
Gestational diabetes
Effects of thyroxine during starvation
Increased gluconeogenesis, glycogenolysis, proteins breakdown, lipolysis and increased glucose uptake from gut
Overall weight of liver
Largest lobe of the liver
1.5 to 2 kg
Right
Functional unit of the liver
Rough structure
Hepatic lobule
Hexagonal shape
Central vein which drains to hepatic vein
At angles branch of portal vein, hepatic artery and bile ducts run.
Portal venous and hepatic arterial blood runs through sinusoids back to central vein.
What cell types line the hepatic lobule sinusoids and function
Hepatocytes - metabolism
Kupffer cells - macrophages - reticuloendothelial
Metabolic functions of the liver
Storage (iron, copper, glycogen, protein, bile, vitamins)
Metabolism (fat, carbs, proteins, bile, hormones, coagulation factors)
Excretion and detoxification
Innumological (Ig production, phagocytosis by kupffer cells)
How much albumin does the liver synthesise per day?
Half-life of albumin and implication clinically
Functions of albumin
200mg/kg/day
20 days - poor indicator of acute liver injury
Colloid oncotic pressure, transport of drugs bilirubin and some hormones
Important globulins synthesised in the liver
Ferritin
Caeruloplasmin
Haptoglobin
Role of haptoglobin
Binding and conservation of free haemoglobin
Vitamin k dependant clotting factors
II, VII, IX, X
Half life of factor 7
Half life of prothrombin
4o
28 days
Overall process of phase one and two drug metabolism
Phase 1 - modification to more polar and hydrophilic
Phase 2 - conjugation to increase solubility and increase renal excretion
Description of phase 1 metabolism
Mainly oxidative
Mediated by cyp enzymes mainly p450
Can involve hydolysis, hydration, reduction, n-oxidation, isomerisation
Overview of phase 2 drug metabolism
Conjugation on relative end groups left by phase 1 metabolism with hydrophilic substance such as glucuronic acid, acetate, sulphate or glutathione
What is the cercadian rhythm of core temperature
Lowest just before waking, highest in evening (0.7oC difference)
What is the typical rise in temp during ovulation
1oC
What forms most of the afferent sensation for thermoregulation
Core sensors, hypothalamus, spine, deep vicera - more important than peripheral sensation!
Where in the hypothalamus senses temp
What part sets temp
Senses at Preoptic area of anterior hypothalamus
Sets temp at posterior hypothalamus
Heat loss responses if warm threshold exceeded
Behavioural - eg removal of cloths
Cutaneous vasodilation
Sweating
Hairs lie flat to skin
Themogenic response if cold threshold exceeded
Behavioural - more cloths, seeking warm environment
Exercise to increase BMR and thus heat production
Cutaneous vasoconstriction
Shivering
Non shivering thermogenesis
Piloerection
How much does shivering raise BMR by
What tempers this response in raising temperature
600%
Causes increased blood flow to peripheral tissues resulting in heat loss
What is non shivering thermogenesis
Where is it most relevant
Adrenaline and na uncouple oxidative phosphorylation so it produces heat instead of atp
Increases heat production 10-15% in adults but most relevant in brown fat in neonates
What drives fever?
Endogenous pyrogens including interleukins, interferons and TNF
These cause local release of prostaglandins in hypothalamus
What is malignant hyperpyrexia
Widespread persistent muscle contraction triggered by stress or specific anaesthetic agents. Causes massive heat production, metabolic acidosis and myoglobinurea.
Underlying issue is defective ryanodine receptors resulting in excessive ca release
Pathological causes of hyperpyrexia
Infection
Malignant hyperpyrexia
Drugs eg ecstasy
Pontine strokes
Neurological effects of hypothermia.
Decreased level of consciousness
Impaired cerebral auto regulation
Neuroprotective?
Cardiovascular effects of hypothermia
Depressed myocardial contractility, reduced myocardial o2 demand
Reduced inotropic effects of catecholamines
Enhanced negative effects of voletiles
Vasoconstriction
Bradycardia and j waves
Decreased cardiac output
Arrhythmias below 32, vf below 28
Respiratory effects of hypothermia
Reduced oxygen demand and delivery
Shift of odc to left
Gases more soluble
Increased tidal volumes
Apnea at 24o
Haematological effects of hypothermia
Increased blood viscosity
Thrombocytopenia (due to sequestration)
Leukopenia
Impaired coagulation (as impaired enzymes)
Poor wound healing and thrombogenic
Immune response to hypothermia
Immune suppression
Metabolic response to hypothermia
Decreased BMR
Increased oxygen uptake due to shivering
Reduced tissue perfusion and metabolic acidosis
Hyperglycaemia
Reduced drug metabolism
Reduced hepatic blood flow
Increased protein catabolism and decreased protein synthesis
Renal effects of hypothermia
Reduced renal blood flow and oligourea
Causes of hypothermia
Exposure
Water/drowning
Old age
Hypothyroid
Prolonged surgery
What neurone type do cold and warm signals travel down
Cold a delta
Wam c
Why is surgery a major risk for hypothermia
Behavioural regulation abolished
Suppresses hypothermic threshold by 3-4o up to 12o post op
Vasodiation from anaesthetics
Sources and percentatages of heat loss during surgery
Radiation - 40%
Convection - 30%
Evaporation 8-15%
Respiratory - 8-10%
Conduction - 5%
