Metabolic Changes in Health and Disease Flashcards
Catabolism
Weight Loss
Anabolism
Weight Gain
How much body energy is lost as heat ?
60%
What does chronic, low-grade systemic inflammation cause ?
As a result of obesity :
Increases the risk of cancer, cardiovascular disease, osteoarthritis and other diseases.
What does obesity cause ?
Increases risk of developing metabolic syndrome and type 2 diabetes.
What controls appetitie enhancement / suppression?
Neuronal and hormonal factors regulate food intake
Describe the role of insulin in metabolism
Insulin :
Hypoglycaemic / Anabolic hormone
- Acts to decrease blood glucose / fuel storage
- Lock nutrients away in storage molecules
Describe the role of glucagon in metabolism
Glucagon :
Hyperglycaemic / Catabolic hormone
- Acts to increase blood glucose levels
- Mobilise energy stores
State the hyperglycaemic hormones
Glucagon
Adrenalin
Cortisol
Growth hormone
(not directly related to absorptive/postabsorptive events)
Give some functions of insulin
Stimulates :
- glucose uptake by cells
- amino acid uptake by cells
- glucose catabolism for energy
- lipogenesis & fat storage
- protein synthesis
Inhibits :
- gluconeogenesis
Give some functions of glucagon
Stimulates :
- glycogenolysis
- lipolysis and fat mobilisation
- gluconeogenesis
Function of metabolic homeostasis
Aims to ensure a constant supply of glucose for the brain (which uses 60% of all glucose produced)
Why does the brain require a constant supply of glucose ?
It is unable to store glycogen or utilise fatty acids (due to blood brain barrier).
State the key regulator of blood glucose
Liver
Buffering via :
- Glycogenesis
- Glycogenolysis
- Gluconeogenesis
State the normal blood glucose range
4-7 mmol/L
OR
70-110 mg/dL
How much energy does a 70kg person use per day ?
1600kcal/day
(up to 5000 active state)
How long do carbohydrate stores last ?
1 day or less - blood glucose will fall
Metabolic changes associated with short-term starvation
Proteins can yield glucose (deamination and gluconeogenesis), but need to be preserved as much as possible.
Muscle shifts to using fatty acids as primary fuel.
Triglycerides have limited ability to be converted to glucose.
Describe glucose sparing for the brain
Muscle shifts to using fatty acids as primary fuel.
Metabolic changes associated with long-term starvation
Ketone bodies build up
Over the 1st few days, the brain becomes more tolerant to lower glucose - uses ketone bodies
Over time the brain gradually increases the use of ketone bodies
The body preserves valuable protein reserves, as need for amino acids to fuel glucogenesis reduced (muscle preserved)
Describe a key feature of long term starvation
Ketone body build up
Brain increases use of ketone bodies (need for glucose reduced)
What is the cause of ketone body build up ?
A consequence of fatty acid breakdown of acetyl-CoA and reduced activity of the citric acid cycle.
State the metabolic changes in fasting
Brain :
- Can only use glucose and ketones for energy
Liver :
- glycogen becomes glucose
Adipose :
- Lipids become free fatty acids and glycerol that enter the blood.
Muscle :
- Glycogen can be used for energy.
- Muscle can use fatty acids
- Muscle protein broken down to amino acids to enter blood
Describe the function of the pancreas
Acts as both an endocrine and exocrine gland
Describe the exocrine function of the pancreas
Digestive enzyme production
Describe the endocrine function of the pancreas
Islets of Langerhans (endocrine cells) are embedded within exocrine tissue
Describe Islets of Langerhans
Composed of 4 cell types, secreting hormones directly into the bloodstream.
- Glucagon in alpha cells
- Insulin in beta cells
- Somatostatin in delta cells
- Polypeptides in PP cells
Exocrine cells
Acinar cells
Endocrine cells
Islets of Langerhans
2% of pancreas mass
Found in clusters of cells
Amylin
Hormone which is involved in regulating appetite and inhibiting glucagon activity.
Insulin
Directs the events of the absorptive state - hypoglycaemic hormone
When are beta cells stimulated to release insulin ?
Rising blood glucose levels
Glucose dependent insulinotropic peptide (GI tract hormone)
Parasympathetic nervous system
When insulin binds to membrane receptors on target cells what is stimulated ?
Translocation of Glut transporters
Facilitated diffusion - 20 fold increase in glucose uptake
Glycogen synthesis (liver/muscle)
Glycolysis
Triglyceride and protein synthesis
Glucagon
Controls blood glucose levels in the post-absorptive/fasting state - hyperglycaemic hormone.
When are alpha cells stimulated to release glucagon ?
Secrete glucagon in response to low glucose
Where does glucagon act ?
Acts mainly on liver (muscle doesn’t have glucagon receptors) :
stimulating :
- glyconeolysis
- gluconeogenesis
What determines the state of metabolism ?
Circulating levels of insulin and glucose
What hormone dominates in the :
a) fed state
b) fasted state
a) Insulin
b) Glucagon
Where is adrenalin & noradrenaline synthesised ?
The adrenal medulla (modified sympathetic ganglion)
Function of catecholamines (adrenaline / noradrenaline)
Targets mainly muscle for glucose
Lower glucose uptake by muscle - metabolise fatty acids instead (glucose sparing)
Increase glucagon secretion / inhibit insulin secretion
Function of the sympathetic nervous system ?
Plays a crucial tole in increasing glucose
Adipose tissue also supplied with sympathetic fibres : growth hormone, thyroxine.
What is diabetes mellitus ?
Chronic metabolic disease resulting form deficient secretion or action of insulin.
How is diabetes mellitus characterised ?
BY elevated blood glucose / chronic hyperglycaemia.
What causes Type 1 diabetes ?
10% of cases
An autoimmune condition in which Beta cells are destroyed - no insulin released.
Genetic predisposition ?
Environmental trigger
What causes Type 2 diabetes ?
90% of cases
Mostly associated with lifestyle
Genetic component (also)
Describe the results of Type 2 diabetes
Tissues become insensitive to the effects of insulin-resistance
Treatment of Type 2 diabetes
Lifestyle changes - diet + exercise
Hypoglycaemic drugs (insulin)
Health consequences of hyperglycaemia
Lack of sensitivity to insulin (increase in blood glucose)
Dehydration
Tissue Injury
Peripheral Neuropathy
Autonomic Nerve Dysfunction
Describe tissue injury caused by hyperglycaemia
Prolonged hyperglycaemia damages blood vessels
Poor circulation
Increased risk for MI
Stroke
Kidney disease
Blindness
Describe dehydration caused by hyperglycaemia
Osmotic pressures caused by glucose in renal tubules
Decreased water reabsorption
Polyuria
Intra/extra cellular dehydration
Increased thirst and hunger
Describe how excess urination occurs
XS glucose cannot be reabsorbed via the proximal convoluted tubules.
Increased osmotic strength of urine - less water reabsorbed
Urine volume greatly increases and this explains sweet urine.
IN serve cases, acidic ketone bodies add to osmotic strength.
State the metabolic consequences of hyperglycaemia
Due to lack of insulin/insulin resistance, metabolism is similar to prolonged fasting/starvation.
High glucose availability.
Describe what happens when there is an increased utilisation of fats
Glycolysis slows
Gluconeogenesis stimulated (using amino acids)
New glucose and ketone bodies circulate in blood
Metabolic acidosis - increased ketone bodies
