Metabolism Physio Flashcards
Define metabolism
Metabolism: the sum of the chemical reactions that take place within each cell
What are the four main pathways for the metabolism of dietary components?
Dietary components metabolized through four main pathways
•Biosynthetic
•Fuel storage
•Oxidative processes
•Waste disposal
What is an anabolic process?
Anabolic
•Synthesise larger molecules from smaller components
- bosynthetic
- fuel storage
What is a catabolic process?
Catabolic
•Break down larger molecules into smaller components
- oxidative
- waste disposal
What does catabolism provide?
Provides energy from fuel molecules via the ATP cycle
ADP + Pi -> energy production via oxidation of carbohydrates, lipids and proteins -> ATP -> energy utilization
What are essential amino acids?
9 essential amino acids
Essential amino acids are not made by the human body and must instead be acquired from our diet. Non-essential amino acids, by contrast, are synthesized by the human body.
11 non essential amino acids
What are the fuels in the diet?
Essential amino acids
•Essential fatty acids
•Vitamins
•Minerals
•Water
•Xenobiotics
What are essential FA?
- cannot be synthesized by the body (or not in adequate amounts) and is therefore essential to the diet.
E.g. alpha linoleic acid and linolenic acid (primary essential FAs)
What is DEE?
DEE: Daily energy expenditure
Main names and formula of carbs?
Monosaccharides and disaccharides
•Glucose C6H12O6
•Fructose C6H12O6
•Galactose C6H12O6
•Sucrose C12H22O11
•Lactose C12H22O11
What are AA composed of?
Amino acids in chains
•Carbon
•Oxygen
•Hydrogen
•Nitrogen (+/- 16% by weight)
What is the daily protein requirement?
Protein requirement: 0.8g/kg/day
What are triglycerides?
Type of lipid
3 fatty acids esterified to one glycerol moiety
•More reduced than other energy sources
•“saturated” – all carbons bonded with hydrogen
What is the storage of excess dietary fuels?
- Fat - Adipose tissue (only 15% water)
- As triaglycerides (approx. 15 kg) - Carbohydrate
– As glycogen in liver (up to 200 g) and muscle (150 g) - Protein – Muscle (80% water)
•In muscle (approx. 6 kg)
How much energy per gram of carb, protein, alcohol and lipid?
- 4
- 4
- 7
- 9
What is BMR?
The energy needed to stay alive at rest
What is energy used for?
Energy used for:
•Respiration
•Cardiac contraction
•Biosynthetic processes
•Tissue repair and regeneration
•Ion gradients across cell membranes
When does BMR apply?
Applies when:
•Post-absorptive (12 hour fast)
•Lying still at physical and mental rest
•Thermo-neutral environment (27-29 oC)
•No tea/coffee/nicotine/alcohol in previous 12 hours
•No heavy physical activity in previous 24 hours
•Establish steady state (30 mins)
What lowers BMR?
Lowers BMR/RMR:
•Age
•Sex
•Dieting/starvation
What raises BMR?
Raises BMR/RMR:
•Body weight (BMI)
•Hyperthyroidism
•Low ambient temperature
•Fever/infection/chronic disease
How do you calculate BMR?
Harris Benedict Equations (2019)
•Schofield Equations (1985)
•Henry Equations (2005)
Rough estimate:
1 kcal/kg body mass/hour
NHS nutrition guidelines (NICE 2006) recommend
25-35 kCal/kg/day for patients who are not severely ill or injured, nor at risk of re-feeding syndrome
What does starvation involve?
Overnight fast
•↓ insulin secretion
•Glycogenolysis
Brain requires approx. 150 g glucose / day
•After an overnight fast, liver has about 80 g glycogen
•Longer fasts necessitate gluconeogenesis (make glucose from non-CHO sources)
What triggers gluconeogenesis?
↓ insulin secretion
•↑ cortisol secretion
Gluconeogenesis uses:
•Lactate
•Amino acids (muscle, intestine, skin breakdown)
•Glycerol (fat breakdown)
What happens in starvation beyond 4 days?
Liver creates ketones from fatty acid
•Brain adapts to using ketones
•BMR falls - accommodation
What is malnutrition?
A state of nutrition with a deficiency, excess or imbalance of energy, protein or other nutrients, causing measurable adverse effects.
Adverse effects on tissue/body shape/size/composition, body function and clinical outcome.
What are essential nutrients needed for?
•Co-factors in metabolism
•Gene expression
•Structural components
•Antioxidants
What is vitamin C like?
Vitamin C
•Ascorbic acid
•Fruit and vegetables
Needed for:
•Heat labile
•Collagen synthesis
•Improve iron absorption
•Antioxidant
What is vitamin B12 like?
Vitamin B12
•Cobalamin
•Protein synthesis
•DNA synthesis
•Regenerate folate
•Fatty acid synthesis
•Energy production
Give examples of vitamins, A, B, D,E and K?
Vitamin A (Retinol)
B Vitamins (Thiamin (B1), Riboflavin (B2), Niacin (B3), Pantothenic acid, Vitamin B6, Biotin, Folate, Cobalamin (B12)
Vitamin D (Calciferol)
Vitamin E (Tocopherol)
Vitamin K (Phylloquinone, Menaphthone)
What is the prudent diet?
5+ servings of fruit/vegetables
•Base meals around starchy carbohydrates
•No more than 5% energy should come from free sugars
•0.8 g/kg/day protein
•Saturated fat: no more than 30 g/day for men & 20 g/day for women
•No more than 2.4 g/day of sodium (6 g salt)
•No more than 14 units alcohol / week (over at least 3 days)
•Adequate calcium
What are the sourced of energy in the body?
oCarbohydrates
oWe have enough glycogen to sustain energy levels for 12 hours.
oFats
oLipid energy reserves provide energy for up to 12 weeks
oProtein
oUsed when muscle glycogen stores fail.
What are fatty acids like?
Carboxylic head group with aliphatic tail.
•Saturated and unsaturated.
Where are FA derived from?
Most are derived from triglycerides and phospholipids.
What occurs in lipid absorption and transport?
- Bile salts emulsify dietary fats in the small intestine, forming mixed micelles.
- Intestinal lipases degrade triacylglycerols.
- Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triglycerides
- Triacylglycerols are incorporated, with cholesterol and apoproteins, into chylomicrons
- Chylomicrons move through the lymphatic system and bloodstream to tissues.
- Lipoprotein lipase, activated by apoC-2 in the capillary releases FAs and glycerol
- Fatty acids enter cells.
- Fatty acids are oxidized as fuel or reesterified for storage.
Where are FAs activated? How?
Fatty acids must be activated in the cytoplasm before they can be oxidised in the mitochondria.
•If the Acyl-CoA has < 12 carbons – can diffuse through mitochondrial membrane
•Most dietary fatty acids have > 14 carbons – Taken through mitochondrial membrane using the carnitine shuttle.
What occurs in fatty acid Beta oxidation?
How is acetylene CoA utilised?
Where are ketones produced?
In the liver from acetyl-CoA.
•Have a characteristic fruity/nail polish remover-like smell.
What happens to acetyl CoA in high rates of FA oxidation?
During high rates of fatty acid oxidation, large amounts of acetyl-CoA are generated.
•This exceeds the capacity of the TCA cycle which results in ketogenesis.
What occurs in ketogenesis?
Acetoacetate can undergo spontaneous decarboxylation to acetone, or be enzymatically converted to beta-hydroxybutyrate.
•Ketone bodies utilised by extrahepatic tissues through conversion of beta-hydroxybutyrate and acetoacetate to acetoacetyl-CoA.
•This requires the enzyme acetoacetate:succinyl-CoA transferase, which is found in all tissues but hepatic tissue.
How is ketogenesis regulated?
Ketogenesis is affected by several factors:
oRelease of free fatty acids from adipose tissue.
oA high concentration of glycerol-3-phosphate in the liver results in triglyceride production, whilst a low level results in increased ketone body production.
oWhen demand for ATP is high, acetyl-CoA is likely to be further oxidised via the TCA cycle to carbon dioxide.
oFat oxidation is dependent upon the amount of glucagon (activation) or insulin (inhibition) present.
What is the CR of ketogenesis?
During normal physiological conditions the production of ketones occurs at a low rate.
•Carbohydrate shortages cause the liver to increase ketone body production from acetyl-CoA.
•The heart and skeletal muscles preferentially utilise ketone bodies for energy preserving glucose for the brain.
What is ketoacidosis?
Occurs in insulin-dependent diabetics when dose is inadequate or because of increased insulin requirement (infection, trauma, acute illness).
•Is often the presenting feature in newly diagnosed type 1 diabetics.
•Also occurs in chronic alcohol abuse.
•Patients present with hyperventilation and vomiting.
What is diabetic ketoacidosis?
Diabetic Ketoacidosis
- Insulin deficiency
- Inhibition of glycolysis and stimulation of gluconeogenesis
- Glycogen breakdown and inhibition of glycogen synthesis
- Increased lipolysis (increased free fatty acids)
- Hyperglycaemia (2 of 2)
- Increased acetoacetate and beta-hydroxybutyrate
What is alcoholic ketoacidosis?
Alcoholic Ketoacidosis
1.High Blood EtOH Concentration. Depleted protein and carbohydrate stores
- Impaired gluconeogenesis
- Decreased insulin and increased glucagon production
2/3. Increased lipolysis (increased free fatty acids)
- Increased ketone production
What is the consequences of ketoacidosis?
Ketones are relatively strong acids (pKa ~ 3.5).
•Excessive ketones lower the pH of the blood.
•This impairs the ability of haemoglobin to bind oxygen.
Ph - low
pO2 - high
pCO2 - low
HCO3 - low
Define homeostasis
maintenance of a constant internal environment
What are teh communication systems?
Endocrine -hormones
Nervous - electrical
What are the categories of communication?
Autocrine
Paracrine
Endocrine
What is autocrine?
Cells talking to themselves.
What is paracrine?
Cells talking to neighbouring cells a short distance away
Signal diffuses across gap between cells
• Inactivated locally, so doesn’t enter the blood stream
What are examples of paracrine?
Interleukins
•Signalling in the immune system
•Mainly between white blood cells
Platelet derived growth factor (PDGF)
•Released from platelets
•Regulates cell growth
What is endocrine?
Cells talking to other cells elsewhere in the body.
What are the endocrine organs/glands?
Hypothalamus
• Pituitary
•Thyroid
• Adrenals
• Pancreas
• Ovaries
• Testes
Define a hormone
Molecule that act as a chemical messenger
Classified according to structure;
●Amino-acid derivatives
●Peptide
●Steroid
What are AA hormones?
Synthesised from tyrosine
●Example; adrenaline
What are peptide hormones?
Made of amino acids
●Vary in size from few amino acids to small proteins
●Some have carbohydrate side chains (glycoproteins)
●Hydrophillic (like water)
How are peptides and AA hormones similar?
Produce a quick reaction in the body
How does the peptide hormones insulin work?
Pancreatic cell:
- Hormone pre-made and stored in cell ready to be released when needed.
- Hormone dissolved in blood.
- Receptor on cell membrane.
- Chemical reaction produces quick response from cell.
(Signal transduction cascade)
Liver cell
What are steroid hormones like?
All made from cholesterol
●Different enzymes modify molecule to produce a variety of hormones
●Can’t dissolve in water
●Can dissolve in lipids
What type of response do steroid hormones produce?
Steroid hormones produce a slow response
How does the steroid hormone testosterone work?
Testes:
Testosterone made by cell and diffuses out once made
Transported in blood bound to transport protein as can’t dissolve in water
Receptor is in the target cell
Slow response as directly affects DNA
What occurs in a positive feedback loop?
Signal amplified
What is the homeostasis model for glucose?
Set point - normal blood glucose (- 4-8mmol/L)
Sensor (pancreas)
Control centre (pancreas)
(Insulin) -> Effectors (liver and muscle)
Regulated variable (blood glucose)
What is involves in a negative feedback loop?
What is the water distribution in a 70Kg male?
- Total body water:
60% of body weight, 42L - Intracellular fluid:
40% of body weight, 28L - Extracellular fluid:
20% of body weight, 14L - Intravascular: 3L
- Interstitial: 11L
What is the movement of water like?
Water is freely permeable through ICF and ECF
●Determined by osmotic contents
●Any change
water shift.
●Always equal = isotonic
What ions affect ECF and ICF?
ECF;
●Sodium is the main contributor to ECF osmolality and volume
●Anions chloride and bicarbonate.
●Glucose and urea
●Protein = colloid osmotic pressure (oncotic)
●ICF
●Predominant cation is potassium
Where is interstitial fluid and plasma?
Interstitial Fluid surrounds the cells, but does not circulate.
•Plasma circulates as the fluid component of blood.
What is plasma osmolality?
●Largely determined by sodium and associated anions
●Estimated plasma osmolality =
2[Na] + 2[K] + urea + glucose mmol/L
●Intra- and extracellular osmolality are equal
●Change in plasma osmolality pulls or pushes water across cell membranes
What is fluid like under normal circumstances?
Under normal circumstances fluid intake = fluid loss
Normal Water gain and loss?
Food and drink
Metabolism
Skin
Lungs
Urine
Fences
Why don’t we give water intravenously?
It is hypo-osmolar/hypotonic vs cells
●Water enters blood cells causing them to expand and burst: haemolysis
●However, this only occurs in the vicinity of the intravenous cannula
●If you could achieve instantaneous mixing it wouldn’t occur
What is ECF osmolality?
ECF Osmolality
●Is very tightly regulated
●Changes in ECF osmolality lead to a rapid response
●Normal plasma osmolality 275-295 mmol/kg
●Water deprivation or loss will lead to a chain of events
Summarise water homeostasis
- Water deprivation/Dehydration
- ↑ECF Osmolality
- Movement of water from ICF to ECF
- Release of ADH from posterior pituitary
- Stimulation of thirst centre in hypothalamus
- ↑water intake
- Renal water retention
- Restores ECF osmolality
What is the effects of ADH?
What happens to ECF volume?
What is the purpose of RAAS?
What occurs in RAAS?
How does dehydration present?
●Thirst
●Dry mouth
●Inelastic skin
●Sunken eyes
●Raised haematocrit
●Weight loss
●Confusion – brain cells
●Hypotension
What is water homesostasis like with excess of water?
- Water excess
- ↓ECF Osmolality
- Movement of water into ICF
- Inhibition of ADH from posterior pituitary
- No stimulation of thirst centre in hypothalamus
- Increased urine volume
- Risk of cerebral overhydration if acute excessive intake
i.e. water intoxication
What causes hyponatremia?
Hyponatraemia
●Cerebral overhydration
●Headache
●Confusion
●Convulsions
What is Hydrostatic pressure?
Hydrostatic pressure
Pressure difference between plasma and interstitial fluid
Water moves from plasma into interstitial fluid
What is oncotic pressure?
Oncotic pressure
Pressure caused by the difference in protein concentration between the plasma and interstitial fluid
Water moves from interstitial fluid into plasma
What is osmotic pressure?
What is oedema?
Oedema
●Excess accumulation of fluid in interstitial space
●Disruption of the filtration and osmotic forces of circulating fluids
●Obstruction of venous blood or lymphatic return
●Inflammation;↑capillary permeability
●Loss of plasma protein
Oedema vs serous effusion?
Oedema
Excess water in interstitial tissue spaces
Serous effusion
Excess water in a body cavity
What is the pathogenesis if oedema and serous effusion?
Oedema and serous effusion
Oedema Serous effusion
Pathogenesis
Increased fluid leakage into interstitial spaces OR
Impaired reabsorption of fluid
Inflammatory
Venous
Lymphatic
Differences between oedemas?
Hypoalbuminaemic
Lymphatic
Venous
Inflammatory
What is pleural effusion?
The normal pleural space contains ~10 mL of fluid
●Balance between
●hydrostatic and oncotic forces in the visceral and parietal pleural vessels.
●lymphatic drainage.
●Pleural effusions result from disruption of this balance
What occurs in a pleural effusion?
In a pleural effusion, different fluids can enter the pleural cavity.
●Transudate is fluid pushed through the capillary due to high pressure within the capillary.
●Low protein content
●Exudate is fluid that leaks around the cells of the capillaries caused by inflammation &↑permeability of pleural capillaries to proteins.
●High protein content
How is pleural fluid protein measured?
Pleural fluid protein is measured to differentiate between exudative (eg malignancy, pneumonia) and transudative (eg LVF, cirrhosis, hypoalbuminaemia, peritoneal dialysis) effusions.
●Exudates have a high protein level compared to transudates
●(and may also contain cells, bacteria, enzymes)
What are the disorders of plasma sodium?
Normal (reference) range 135 -145 mmol/L
●Concentration is a ratio, not a measure of total body content
●High or low [Na] are more often due to gain or loss of water, rather than Na
●Clinical effects are on the brain due to constrained volume (skull)
●Rate of change is more important than absolute levels
What are the causes of hypernatremia?
Hypernatraemia (↑ Na+) e.g.
• Water deficit:
•Poor intake
•Osmotic diuresis
•Diabetes insipidus
• Sodium excess:
•Mineralocorticoid (aldosterone) excess
•Salt poisoning
What are the causes of hyponatremia?
Hyponatraemia (↓ Na+) e.g.
• Artefactual
• Sodium loss
•Diuretics
•Addison’s disease
• Excess water
•IV fluids (iatrogenic)
•SIADH
• Excess water ++ and sodium +
•Oedema
What are the effects of hyper/hyponatraemia?
Hyper - Cerebral intracellular dehydration (tremors, irritability, confusion)
Hypo - Cerebral intracellular over-hydration (headache, confusion, convulsions)
Name the essential amino acids
histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
