Wk 22 Flashcards
Energy intake and expenditure…
What is energy intake defined as?
What is energy expenditure?
The amount of energy units (KJ/Cal) consumed from foods (modulated by hunger)
Internal heat and external work
What is internal heat? (under the category of energy expenditure)
- Basal metabolic rate= minimum amount of energy expenditure at rest to maintain life (breathing, circulation, etc)
- Thermic effect of food= energy invested in digestion and absorption of nutrients
What is external work? (under the category of energy expenditure)
energy invested in environmental interaction
What is positive energy balance?
What is negative energy balance?
Positive: Energy intake > energy expenditure
So eventually gain weight
Negative: Energy intake < energy expenditure
So eventually lose weight
Main preventable and pathological causes of positive energy balance=
Main preventable and pathological causes of negative energy balance=
Pos:
- Sedentary lifestyle and overeating
- Hypothyroidism/ hormonal imbalance (Cushing’s), drugs (steroids) and oedema
Neg:
- Fasting or lack of access to food
- Digestive disease, loss of appetite, hyperthyroidism, Anorexia Nervosa
What is the average daily energy intake for a healthy adult?
How much of this is... Carbs Fat Simple sugars Protein Dietary Fiber Sodium
Ave daily expenditure for men and women in cal:
8700 KJ (~2000 Cal)
Carbs: 300 g Fat: 90 g Simple sugars: 90 g Protein: 50 g Dietary Fiber: 30 g Sodium: 3 g
Women: 2000 cal
Men: 3000 cal
What are the 4 GIT sensors that regulate appetite?
What are 2 other tissue sensors?
Ghrelin
CCK
Peptide YY and Pancreatic polypeptide
Insulin and Leptin
What does Ghrelin do and where is it produced?
Ghrelin:
- Acts on the hypothalamus to increase hunger, increases gastric acid secretion and GIT motility
- Produced by stomach when empty and stops being produced when stretch receptors are activated
What does CCK do and when is it released?
CCK:
- Acts on hypothalamus to increase hunger, stimulates pancreatic/ gall bladder secretion and GIT motility
- Released from GIT postprandially (after a meal)
What does Peptide YY and pancreatic polypeptide do and where are they released?
They both do the same thing:
inhibit food intake
Peptide YY is released by distal intestine and panceratic polypeptide is released by pancreas and distal gut
What does insulin do? (in regards to appetite)
Supresses appetite
- Signals the nutritional status to the brain (circulates at levels proportional to fat mass so inhibits hunger when levels are high)
What is Leptin and what does it do?
It is a major adipokine produced by adipose tissue
- Circulates at levels proportional to fat mass= inhibits hunger response when levels are high
What is satiety?
The satisfied feeling of being full after eating
What does decreased sensitivity to leptin lead to?
Decreased sensitivity to leptin= inability to detect sateity which means people will keep eating even when their stomach is full= obesity
What is the main effector organ in appetite regulation?
Hypothalamus
Through what nerve does the hypothalamus control GIT secretions and motility (and also stimulate thyroid)?
Vagus nerve
Describe the steps of the Hypothalamic-pituitary-thyroid (HPT) axis (3)
What does the product do?
Hypothalamus releases thyrotropin releasing hormone (TRH)
TRH tells pituitary to release thyroid stimulating hormone
TSH tells thyroid to release Triiodothyronine (T3) and thyroxine (T4- prohormone)
T3 increases HR, ventilation rate, increases catabolism of proteins and increases basal metabolic rate= greater use of energy stores= weight loss
(T3 also increases body heat production)
Hypothalamic-pituitary-adrenal (HPA) axis…
What is it activated by?
What are the steps? (3)
What does the product do?
Activated by stress, illness, physical activity and the sleep/wake cycle
Hypothalamus releases corticotropin releasing hormone (CRH)
CRH tells pituitary to release adenocorticotropic hormone (ACTH)
ACTH stimulates adrenal glands to release cortisol
Cortisol
- Increases blood glucose by stimulating gluconeogenesis
- Supresses immune system (less demand for energy)
How does cortisol indirectly increase metabolic rate?
It increases the availability of glucose
How does exercise increase basal metabolic rate?
It increases muscle mass and muscle has a higher resting metabolic rate
What is the normal range for blood glucose?
What regulates this?
4 to 7.8 mmol/L
Pancreas
What concentration is hypoglycaemia?
Acute or chronic problem?
How to treat?
<4mmol/L
Acute
Glucose
What concentration is hyperglycaemia?
Acute or chronic problem?
What is the most common pathology related to?
> 8mmol/L
Chronic
Blood vessels
What are the cells in the islets of langerhans (endocrine pancreas) and what peptide hormones do they produce?
a cells= produce glucagon
B cells= produce insulin
o cells= produce somatostatin/ GHIH
F cells= produce pancreatic peptide
What does insulin do? (in regards to blood glucose)
What does glucagon do?
Reduces blood glucose (glucose storage)
Increases blood glucose (liberation of stored glucose)
How is insulin produced?
Produced in pre-pro peptide form so requires 2 cleavage events to become active hormone
How is insulin secreted?
Increase blood glucose conc is detected by pancreatic cells via GLUT2 receptors
Increased cellular glucose (from GLUT2 receptors) stimulates entry of Ca into same cell
High intracellular Ca promotes exocytosis of vesicles filled with insulin
The number of receptors determines the sensitivity of cell to hormone…
What is upregulation and what does it lead to?
What is down regulation and what does it lead to?
- Contributes to what disease?
Upreg= more receptors (increased sensitivity)
Downreg= fewer receptors (decreased sensitivity)
Downreg contributes to hormone resistance (e.g. insulin resistance [T2 diabetes])
Describe the general GPCR signalling
Ligand (hormone) binds to receptor and this activates G protein
G protein activates adenylate cyclase
Activated adenylate cyclase converts ATP to cAMP (2nd messenger)
cAMP is a 2nd messenger to activate protein kinases (protein kinases phosphorylate cellular proteins)
Millions of phosphorylated proteins= cell response
How does insulin cause glucose uptake into cells?
Insulin increases GluT4 insertion into plasma membranes
Translocation of GluT (glucose transporters) allows facilitated diffusion of glucose into cells
(facilitated diff= no energy required but need conc gradient)
Glucose concentration maintenance…
Blood glucose increased by:
Blood glucose decreased by:
Glycogenolysis (in liver) and Gluconeogenesis (in liver)
Glycogenesis (in liver and skeletal muscle)
Adipogenesis (in adipocytes)
What is normal glucose level in blood?
90mg/100ml
What happens when blood glucose increases?
Pancreas releases insulin that stimulates glucose uptake by cells and also stimulates liver to make glycogen from glucose (glycogenesis)
What happens when blood glucose decreases?
Pancreas releases glucagon which tells the liver to break down glycogen into glucose (glycogenolysis)
What is gluconeogenesis?
What hormones does it require?
Conversion of lipids and proteins (also glycogen?) into glucose (in liver)
Cortisol (to act on adipocytes for lipolysis and other tissues for proteolysis) and glucagon
Lipolysis…
When does it occur?
How does it occur?
How are the products carried?
In response to stress hormones (cortisol and adrenalin)
Adrenalin activates hormone sensitive lipase (HSL) in adipocytes
HSL breaks down triglycerides into FFAs and glycerol, releasing them
Carried in lipoproteins or attached to proteins (albumin)
What is adipogenesis stimulated by?
What does adipogenesis lead to?
Stimulated by insulin
Increased uptake of glucose and free fatty acids (increased triglyceride synthesis)
What is lipolysis stimulated by?
What is lipogenesis stimulated by?
Lipolysis stimulated by adrenalin, NA and cortisol
Lipogenesis stimulated by insulin
What is protein synthesis stimulated by?
Insulin
What does the rate and amount of drug delivery depend on? (once in systemic circulation after 1st pass metabolism)
(5)
- Cardiac output
- Regional blood flow
- Capillary permeability
- Tissue volume
- Tissue affinity for drug
Where is most of the fluid in the body?
Inside cells
What are the 3 most perfused organs? (receive drug first)
Liver
Kidney
Brain
What organs have the largest volume so store larger amount of drug?
(2)
Muscle
Adipose tissue
Diffusion occurs rapidly for what drugs…
small or large
Lipophilic or hydrophilic
Ionised or non-ionised
Small, lipophilic non-ionised drugs easiest to absorb
What carrier plasma protein binds acidic drugs?
What binds basic drugs?
albumin
a1-acid glycoprotein
What prevents diffusion through the blood-brain barrier?
tight junctions between epithelial cells
What is an example of a blood brain barrier efflux transporter and what does it do?
p-glycoprotein
Pumps xenobiotics (e.g. drugs) out of CNS so the drug has no effect in brain
What is the volume of distribution and what does it represent?
Vd= amount of drug in body (out of the amount of drug in blood/plasma)
It represents the extent of drug distribution to tissues and not to plasma
What does high Vd mean?
What does low Vd mean?
High Vd means the drug has been highly distributed into tissues
Low Vd means the drug is staying in the blood
How does obesity affect drug absorption?
How does it affect tissue perfusion? (cardiac, liver)
There is more adipose tissue so lipophilic drugs can store there in much higher quantities
It reduces tissue perfusion and cardiac structure/ function may be changed and fatty liver alters drug metab/ clearance
