Endocrine system 4 Flashcards
What is whole body metabolism?
Co-ordinated regulation of etabolic pathways in different organs to maintain adequate energy supply to all cells
1 - Storage of nutrients/break down of stores when required
2 - Maintenance of blood glucose = primary energy source of the brain
What is anabolism?
The use of chemical energy to build up macromolecules from precursors
What is catabolism?
The breakdown of macromolecules to generate chemical energy
What can whole body metabolism be divided into?
- Fed (or absorptive) state → Anabolic
- Fasted (or post-absorptive) state → Catabolic
Summarise the bimolecule processing (how it is used) of carbohydrates:
Carbohydrates –> glucose
Glucose —> glycoen (via glycogenesis)
Glycogen —> glucose (via glycogenolysis)
(In the liver, Skeletal muscle)
Total energy store = 1%
Summarise the bimolecule processing (how it is used) of lipids:
Lipids –> free fatty acids glycerol
Free fatty acids glycerol —> triglycerides (via lipogenesis)
Trigylcerides —> free fatty acids glycerol (via lipolysis)
(Adipose)
Total energy store = 77%
Summarise the bimolecule processing (how it is used) of proteins:
Proteins –> amino acids
Amino acids —> proteins (via protein synthesis)
Proteins —> amino acids (via protein breadown)
(Skeletal muscle)
Total energy store = 22%
Describe the energy balance formula:
Energy input = energy output
Energy input = work performed + heat produced
What can each of the part sof this formula be broken down into:
Energy input = work performed + heat produced
Energy input = food intake & energy from nutrients
Work performed = ~40% - mechanical, chemical, transport
Heat produced = ~60% - maintain body temp
What is positive energy balance?
Energy input > energy output
- Energy in excess of output gets stored
What is negative energy balance?
Energy input < energy output
- Net breakdown of macromolecules to provide energy
What is energy metabolism during fed (absorptive) state like?
- 3-4 hours following meal, nutrients in the bloodstream are plentiful
- Energy input > energy output
- Hormonal control: insulin = anabolic
What is metabolism during fasted (post-absorptive) state like?
- Between meals, energy stores must be mobilised = catabolic
- Energy input < energy output
- Hormonal control: glucagon & other counter-regulatory hormones to insulin
- Maintain energy source for brain and other neuronal tissue
Regulation of insulin release:
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What can happen to glucose in the liver?
- Glycogen synthesis (inc glucose levels)
- Glycogen breakdown (dec glucose levels)
- Gluconeogenesis (dec glucose levels)
What can happen to glucose in the muscle?
- Glucose uptake - via GLUT-4 (inc glucose)
- Protein synthesis (inc glucose)
- Protein breakdown (dec glucose)
What can happen to glucose in adipose tissue?
- Glucose uptake - via GLUT-4 (inc glucose)
- Lipogenesis (inc glucose)
- Lipolysis (dec glucose)
What is the main action of insulin?
Red blood glucose
Mediated by insulin receptors (tyrosine kinase receptor family)
Effect of insulin on glucose uptake (SkM, adipose)
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What is the release of glucagon stimulated by?
- Stimulated by low blood glucose (<3.5mmol/L or mM) para- and sympathetic NSs
- Inhibited by high blood glucose
What are the actions of glucagon?
Raise blood glucose
- Stimulate hepatic glycogenolysis
- Stimulate hepatic gluconeogenesis
- Simulate lipolysis
Describe the actions of how blood glucose is lowered when too high:
- alpha-cell produces less glucagon
- beta-cell produces more insulin
Dec blood glucose = back to normal
Describe the actions of how blood glucose in increased when too low:
- alpha cell produces more glucagon
- beta-cell produces less insulin
Inc blood glucose = back to normal
What is the normal range of blood glucose?
4-8mmol/L
What happens when blood glucose in raised?
- Glucose production dec
- Glucose utilisation inc (glucose uptake & use)
- Insulin lowers blood glucose
What happens when blood glucose is too low?
- Glucose utilisation dec
- Glucagon, adrenaline, growth hormone & cortisol produce glucose vie glycogenolysis & gluconeogenesis
- Counter-regulatory hormomes to insulin raise blood glucose
Why is insulin & glucagon working together important?
Insulin & glucagon work as a team = most important regulators of normal fuel metabolism
What is overall involved in glucose homeostasis?
Glucose production: GLUCAGON, adrenaline, growth hormone & cortisol via;
- Glycogenolysis
- Gluconeogenesis
Glucose utilisation: INSULIN via;
- Glucose uptake & use
When does hypoglycaemia occur?
< 4mmol/L of glucose
What are the symptoms of hypoglycaemia?
Palpitation, tremors, sweating, anxiety
- Counter-regulatory activity of SNS
Loss of concentration, slurred speech, seizures, loss of conciousness, coma
- Glucose deficiency in brain
When does hyperglycaemia occur?
> 7 mmol/L fasted
11mmol/L
What are the symptoms of hyperglycaemia (include acute & chronic)?
Increased volume/frequencey of urination, thirst, dehydration
- ACUTE (>40 mmol/L): confusion, high temperature, seizure, come
- CHRONIC: Long-term complications, such as CVD (MI, stroke), nephropathy, retinopathy, neuropathy
What does inappropriate glucose homeostasis lead to?
Diabetes mellitus (chronic hyperglycaemia)
This is the most common endocrine disorder
What is diabetes mellitus?
Chronic metabolic disorder charaterised by hyperglycaemia, cased by:
- Insulin deficiency (Type 1) 5-15%
- Impaired beta-cell function and/or loss of insulin sensitivity (insulin resistance) (Type 2) 85-95%
What are the 2 types of diabetes mellitus?
- Insulin deficiency (Type 1) 5-15%
- Impaired beta-cell function and/or loss of insulin sensitivity (insulin resistance) (Type 2) 85-95%
What are the clinical features of Diabetes mellitus?
- Direct concequences of high blood glucose levels
- Metabolic concequences of imapired glucose utilisation
- Long-term complications of diabetes
What are the direct concequences of high blood glucose levels in diabetes?
- Glucosuria (glycosuria), polyuria (due to osmoticc diuresis), polydipsia (thirst)
- Visual disturbance (altered refracted index of lens)
- Inc urinogenital infections
What are the metabolic concequences of impaired glucose utilisation in diabetes?
- Lethargy, weakness
- Weight loss (T1DM)
- Ketoacidosis (increased fat metabolism, T1DM)
What are the long term complications of diabetes?
- Microvascular: nephropathy, neuropathy, retinopathy
- Macrovascular: ischaemic heart disease, stroke, peripheral vascular disease
What is type 1 diabetes caused by?
Autoimmune - autoantibodies
- Progressvie destruction of islet of beta-cells
When is the onset of diabetes?
Usually <40 years
Rapid onset = pathophysiological changes occur much earlier
Suceptibility genes & environemental triggers = virus & toxins
What is the treatment for type 1 diabetes?
Treatment w insulin
Regular exercise & healthy diet
What is the cause of type 2 diabetes?
- Relative insulin deficiency (impaired beta-cell function) and/or insulin resistance complex
- Impaired insulin signalling pathways
- Nutrient oversupply, cellular stress & inflammation
When is the onset of type 2 diabetes?
Onset ususally >40 (>25 years black, S. asian)
Graudal onset –> suceptibility genes & environmental triggers, reduce physical activity, in calorie consumption
What is the treatment for type 2 diabetes?
- Diet 10-20%
- Drugs 20-90% –> ~20% insulin
What are other possible causes of diabetes?
- Gestational
- Loss of pancreatic function/surgery
- Excess of some hormones?
What are the healthy diet & lifestyle changes needed for diabetes?
- Healthy diet, regular meals
- Lifestyle
- Exercise (improve insulin sensitivity, weight loss)
- Smoking cessation (dec CV risk)
What are the 2 main drug treatments for diabetes?
- T2DM
- T1DM (type 2)
What do T2DM drugs do to treat diabetes?
Improve insulin action
- Metformin, pioglitazone(PPARy agonist)
Promote insulin release
- Sulphonylureas/post-prandial glucose regulators and incretin-based therapies
SGLT-2 inhibitors - decrease renal reabsorption of glucose
What do T1DM drugs do to treat diabetes?
(Inadequate control wiht drugs, pregnancy)
Insulin - exogenous; subcutaneous injection (infusion for emergency/fine control)
