Endocrinology Flashcards
What two factors will effect metabolism?
Genetics and environmental factors
Draw a tree diagram to show how those two actors effect metabolism
Where is growth hormone secreted from?
What responds to it?
Release from somatotrope anterior pituitary cells induced by GHRH (inhibiter somatostatin GHIH)
does not act through a specific endocrine gland as other tropins rather almost all tissues respond to it especially the liver.
What effects does the secretion of GH cause?
What does this result in?
- protein production
- cell size
- cell division
results in tissue grwoth e.g. muscle mass and bone growth
What does GH induce?
Whats the main cause of GH activity?
- GH Induces expression of somatomedins, Insulin Like Growth Factor 1- there are other but this one is turned on by GH (IGF-1) by liver
- main cause of GHs activity as IGF-1has long half life
What response is caused by the expression if IGF-1 ?
- Increases cartilage and bone growth
- Increases amino acid uptake into cells
- Increases RNA transcription and translation (protein production)
- Lower protein catabolism (raises blood AAs)
- Increases lipid breakdown (causes raised blood FFAs)
- Decreases carbohydrate metabolism (causes raised blood glucose)
Tell me some general facts of GH?
- use lipids
- make- and general tissue use less- glucose
- save and produce protein/ AAs
What does the GH somatotropin stimulate?
- GH is secreted in starvation in order to prevent you using protein
- Infection also increases GH
What reduces GH secretion ?
What is altered in order in increase or decrease GH?
Name two hypothalamic hormones which help do this?
these act to be altering hypothalamic tropic hormones
hypothalamic hormones
- Growth hormone-releasing hormone (GHRH)
2 .Growth hormone inhibitory hormone (somatostatin) (GHIH)
Name a downstream control of the GH?
What feedback loop is it?
Somatomedins (IGFs- negative feedback)
What are somatostatin also secreted by?
delat cells at several locations in the digestive system
Draw the flow diagram from the hypothalamus to IGF-1 release ?
The flow diagram as drawn above is a complex regulation system and can lead to loss of responsiveness due to defects at different points. what can this lead to?
- failure in production of hormone
- Failure in response to hormone (pituitary targets)
What can increased GH signalling lead to?
Abnormal repsonses at these points
Whats a growth plate?
The area of growing tissue near the end of long bones in children and adolescents.
Each long bone has at least two growth plates, one at each end
Increased GH can lead to growth defects such as…
- Acromegaly
- Giantism
How do thyroid gland hormones alter metabolism?
Tell me about the thyroid stimulating hormone and what it binds to ?
- 3 AA long
- binds to receptors on thyroid follicle gland
What does T3 and T4 mean?
T3 means 3 iodine groups
T4 means 4 iodine groups
Whats Thyroglobulin?
What does it release and how?
A tyrosine rich store, which is iodinated, reabsorbed and broken down by proteases in lysosomes to release T3 and T4
What is TSH/ thyrotropin released in response to?
cold via action of TRH
What are the actions of TSH?
- Increases number, sizes and activity of cuboidal epithelia in the thyroid gland
- Increases iodide pump
- Increases enzymes for iodination of tyrosine
- Increases thyroglobulin proteolysis
Give an example of a tropic and trophic hormone?
TSH
Draw the structures of T3 and T4
The percentage released from the gland
Thyroxine binding globulin attachment
If thyroxine is injected, when does it have its effect?
About 10 days later
Where is T4 mainly broken down?
In the plasma (loses iodine) so cells mainly see T3
Tell me the half life of T3 and T4
T4 half life: 6 days
T3 half life: one day
Why is T3 more active
Less well bound by binding proteins (in end T3 is 90% of intracellular action)
Tell me what T3 and T4 bind to and what this activates?
Binds to thyroid receptor (nucleus) which then binds Retinoid X Receptor (RXR), activates transcription
Tell me the effects T3 and T4 has on basal metabolic rate
- Increases basal metabolism in almost all tissues
- Increases number and size and activity of mitochondria
- Increase cells leakiness to Na+ –> increases heat production (Na/K/ ATPase more active)
How does T3 and T4 effect carbohydrate metabolism?
- stimulates it
- increases glucose uptake, its production from other metabolites AND its breakdown
How is T3 and T4 involved in fat metabolism?
- stimulates it
- mobilises lipids from adipocytes
- increases beta-oxidation
How does T3 and T4 affect protein synthesis in development ?
- stimulates it
- increases growth of long bones
- in foetal and early life it induces CNS development
Tell me some main facts about T3 and T4?
- Use lipids
- Make and use glucose
- save and produce proteins
Tell me some effects of hyperthyroidism?
- Weight loss
- Sleep less
- exophthalmos (ulcers as dries in sleep)
- tremble due to increase nervous activity
- can be tumours
- feel hot
- weakening of eye muscles
- Stimulatory autoimmune disease on thyroid
- if AutoImmune – inflammation of periorbital fat (Graves Diseases)
- (primary in thyroid, secondary in pituitary) or AI disease with antibodies not killing but stimulating the gland by activating TSH receptors
Tell me some effects of hypothyroidism?
- AI but with destruction of gland
- I2 deficiency
- (goitre) myxoedema: watery collection in tissues
- hyaluronic acid/ chondroitin layer in wrong place
- gain Weight
- Sleep more
- Not stimulatory autoimmune disease
- Cretinism: mental retardation if have an iodine deficient diet
- Feel cold
What does ACTH regulate?
The amount of cortisol in the adrenal cortex
MISTAKE FROM PREVIOUS LECTURE, THIS IS THE RIGHT STATEMENT
There is Less T3 then T4 and most T4 binds to carrier protien
What are the layers of the adrenal gland from inside to out?
Inside
Medulla
Cortex which has the 3 layers:
Zona reticularis
Zona fasciculata
Zona glomerulosa
outside
Tell me the hormones released and an example produced from each tissue area of the drenal gland
Tell me 6 examples of steroid hormones (all steroids are based on cholesterol from the membrane)
- Oestrogens
- Progesterone’s
- Androgens (testosterone)
- Glucocorticoids (cortisol)
- Mineralocorticoids (aldosterone)
- Vitamin D
What does the site of adrenal steroid hormone production depend on?
The enzymes in that zone
e.g. mineralocorticoid produced in zona glomerulosa depends on the aldosterone synthetase
Tell me about the synthesis of steroid hormones?
They are synthesised only when needed, with immediate secretion
Why can’t steroids be stored in the cell?
They are highly lipophilic
Tell me the secretion rates of adrenal steroids in mg/day
Tell me the relative potencies of steroids
give the glucocorticoids effect
give the mineralocoritcoid effect
These are the following steroids:
- cortisol
- corticosterone
- aldosterone
- cortisone
- dexamethason
Which steroids are synthetic?
What are they used for?
How are they commonly applied?
Cortisone and dexamethasone are synthetic
they are used for anti-inflammatory effects
Dexamethasone is an artifical corticosterone and this tends to be injected
Cortisone can be used as a cream
What do ACTH signals increase?
The uptake of cholesterol and debranching of cholesterol to prednisone in the adrenal
Draw the reaction of the formation of corticosterones and cortisol from cholesterol and where ACTH regulates activity and where it induces expression
ACTH regulates the levels of cortisol being produced
(dont need to know about the changes in side chains)
Tell me about the glomerulosa layer
Tell me 2 stimuli for cortisol release
- circadian rhythm
- stress
Where are the following hormones produced and tell me the reaction for secretion of CRH-ACTH-cortisol release?
When are peaks in cortisol seen?
- when you first wake up
- another peak from physical or emotional stress
What is ACTH used as?
A precursor hormone in pituitary gland
what does stress increase release?
20-30 fold, pain acts via CRF/H
What cells express prohormone convertase 1 (not 2) so only these make what?
Only pituitary corticotrope cells express prohormone convertase 1 and (not 2) so only these make ACTH from precursor
What are the controls for glucocorticoids secretion?
What feedback loop is this?
Negative feedback controls for glucocorticoids
Whats the mechanism of adrenocorticoids action?
What are the 3 functional domains of steroid hormone receptors?
- Ligand-binding domain: C-terminal, Ligand-dependent nuclear translocation signal, Chaperone (inhibitory) protein binding domain
- DNA-binding domain: 2 Zn finger motifs (central area of receptor)
- Ligand-dependent transcription activating domain (recruit’s transcriptional co-activators
Tell me the steps to the activation of intracellular receptors?
- steroid shows cytosolic binding
- complex migrates to nucleus
- (cf- thyroid hormone receptors are nuclear)
- hormone binding changes conformation (shape) of the receptor protein
- causes inhibitory protein complex to dissociate and opens up nuclear translocation signal region- receptor/ hormone complex transfers to nucleus
- causes the receptor to bind to coactivator proteins that induce gene transcription
- Receptor activation induces the modulation of transcription of specific genes that have hormone receptor elements (HRE).
What are HREs?
Are short cis-acting sequences located within the promotors or enhancers of target genes
Give 2 examples of steroid hormones HREs
- inverted repeats of AGGTCA (oestrogen receptor)
- Inverted repeats of AGAACA (glucocorticoids receptors)
How is specificity of intracellular receptors given?
- which cells express the receptor
- which cells express the coactivator
What is glucocorticoid secretion dependant on?
CRH –> ACTH –> Cortisol
Where is glucocorticoids found?
They circulate the plasma and are most bound to transcortin (corticosteroid-binding globulin)
Tell me about the unbound glucocorticoids ?
unbound: 5-8% of total cortisol (biologically active)
When unstressed when is peak plasma cortisol and ACTH seen?
around 7am, just before waking
What do glucocorticoids drive and what is this?
They drive catabolism.
This is a metabolic pathway that break down molecules into smaller units and release energy
how do Glucocorticoids cortisol (corticosterone) prevent hypoglycaemia?
Spares general use of glucose and glycogen (saved for CNS and RBCs)
What do corticosterone cause the utilisation of?
Proteins and fats
overall catabolic (breakdown) function
Where is gluconeogenesis initiated?
in the liver
What does gluconeogenesis lower?
The use of glucose by cells which causes raised blood glucose
When is adrenal diabetes caused?
If there is an excess production of cortisol
What is cortisol needed for?
Full activity of glucagon and adrenaline (this helps to prevent hypoglycaemia)
How are corticosterones involved with proteins
- What do they help to reduce?
- What does it increase?
- What does it mobilise?
- Reduces protein content of all tissues except liver –needed liver for gluconeogenesis
- increases protein catabolism and lowers synthesis (e.g. collagen in bones and skin
- Mobilises amino acids from cells (especially muscle)
How are corticosterones involved with lipids?
- increased utilisation /mobilisation of fatty acids for fuel
- loss from dermis and deposition into head and chest
Do corticosterones increase or decrease appetite?
increase
Tell me the basis of corticosterones?
- Overall catabolic (breakdown) functions
- Utilisation of proteins and fats
- Prevents hypoglycaemia
- Spares general use of glucose/glucogen (saved for CNS and RBC)
What effect does glucocorticoids have?
Very potent anti-inflammatory effects (hydrocortisone)
How do glucocorticoids reduce inflammation/ act as immunosuppresants?
- Stabilises capillary membranes
- Reduces release of lysosomal enzymes by WBCs
- Reduces WBC migration
- Suppressed lymphocyte division
- Lysis of lymphocyte
Tell me how cortisol/ corticosterone prepare a medium/ long term response of the body to stress?
The hypersecretion by adrenal glands is due to what?
High glucocorticoids
‘Cushing’s disease’
What does the hypersecretion of adrenal gland cause?
- secondary to hypothalamic tumour (increased CRH)
- secondary to pituitary adenomas (increased ACTH)
- primary tumour in adrenal cortex
Whats iatrogenic increase?
When you’ve been treated with steroids (cushing disease caused by a person being given too much steroids)
Tell me some symptoms of cushings disease…
- High blood glucose- increased drinking/ urination
- Protein loss and muscle weakness
- Mobilisation of fat
body shape change (due to muscle conversion)
- Enhances appetite
greatly (fat deposition – even though more is used)
- Immunosuppressed
What is mineralocorticoids produced by?
what indirectly regulates its levels?
What absorption is it involved in?
What does it modify and how?
- Produced by Zona glomerulosa ACTH needed for secretion but Angiotensin II regulates levels
- NaCl resorption
- Water resorption
- K + ions loss
- Very important (cf High extracellular K+ )
- Modifies blood pressure by increasing extracellular volume by increasing absorption of NaCl and also water with it
- NaCl is balanced by K+ loss
Whats the most potent mineralocorticoid?
Whats its function?
Aldosterone
function: loses K/ retains Na+/ increases BP
Where is the receptor of aldosterone found?
In the distal convoluted tubule and in the collecting duct
Does aldosterone have a carrier protein?
What does this mean?
No carrier protein, so rapidly cleared from plasma (shorter action, lower half life than cortisol)
What does aldosterone increase the expression of?
- apical membrane Na+ channels
- luminal/basal Na/K/H pumps.
- Metabolism
increases Na+ and water resorption and lose of K+ and H+ ions
Tell me about the speed of function of aldosterone?
Relatively slow (~30 mins) acts through transcription pathway (cf ADH’s G proteins /cAMP pathway, therefore ADH is faster as is already located where needed)
The regulation of K+ in the blood is most important in this process
What are the two ways aldosterone release is regulated?
- Renin-angiotensin-system stimulatory
- Atrial Natriuretic factor/hormone (ANF/ANH) Inhibitor
Tell me about the Renin-Angiotensin-system
- Low blood pressure detected by the Juxta glomerular (JG) cells: these are modified smooth muscle cells
- Low Na+ / High K+ in fluid in DCT due to low filtration (low BP) stimulates Macula densa which activates the JG cells
What do JG cells release into the blood and what does this cleave?
JG cells release Renin into the blood, which cleaves
Angiotensinogen (liver) –> Angiotensin1
What is Angiotensin 1 converted to and by what?
What does the product of the above reaction cause?
- Angiotensin 1 converted to Angiotensin 2 by the ACE (Angiotensin-converting-enzyme) on lungs and kidney endothelial cells
- Angiotensin 2 causes vasoconstriction and adrenal zona glomerulosa to secrete aldosterone (corticosterone –> aldosterone)
What is High BP monitored by?
What is produced?
What does it block?
Atrial muscle (expansion), which produces ANF-blocks renin formation
What does Atrial Natriuretic Factor/hormone (ANF/ANH) lower?
lowers Na+ / water reabsorption and hence blood pressure
Where is corticotropin releasing hormone released from?
They hypothalamus
Where is the adrenocorticotropic hormone released from?
The anterior pituitary gland
Tell me about the role of ACTH?
ACTH needed but doesn’t regulate levels of aldosterone, only acting as an on/ off switch. Levels of aldosterone are dependent on levels of renin coming into blood.
What is the failure of adrenal cortex usuaully due to?
give an example?
Autoimmune disease (antibodies damage all cortical cells)
e.g. Addision’s disease
Tell me two effects of Addisons disease?
- reduced aldosterone
- reduced glucocorticoids
Tell me the effects of reduced aldosterone
- loss of Na+ into urine
- increased K in extracellular fluids
- fluid loss
- muscle weakness
- if untreated death due to cardiac arrhythmias
Tell me about effects of reduced glucocorticoids?
- cannot respond to stress
- often not diagnosed till stressed e.g. at surgery
- also increase in ACTH as feedback lost (so more POMC the ACTH precursor formed)
What is the normal blood glucose level?
70-90 mg/100 ml blood
once a meal is eaten, what does the blood glucose level rise to?
Increases to 120mg/100mls in the hour after a meal, but generally maintained between meals and during starvation
What occurs in the liver-blood glucose buffer system?
- a glycogen store
- neoglucogenesis centre
- ketone body former
What does insulin and glucagon act as?
A fine control centre for glucose concentration act with the higher (stress) responses to regulate blood sugar
What hormone does short term hypoglycaemia produce?
nor/adrenaline
(sympathetic system and adrenal gland)
What hormone does long term hypoglycaemia produce?
growth hormone/ cortisol
this induces fat utilisation
Tell me what can occur at different blood glucose levels as it drops?
Fed state means more insulin, what does this increase?
- glucose oxidation
- glycogen synthesis
- fat synthesis
- protein synthesis
Fasted state means more glucagon, what does this increase?
- glycogenolysis
- gluconeogenesis
- ketogenesis
In the krebs cycle, where does acetyl CoA come from?
Glucose or lipids but for this cycle to work you need oxaloacetate
(fat burns in carbohydrate flame)
When starving, what does the liver convert FA to?
ketone bodies- a way of transferring C2 to other organs
Once acetone is made can it be reused?
No
Name 3 ketone bodies used when fatty acids are oxidised?
- beta hydroxybutyrate
- Acetoacetate –> acetone
- acetoacetyl CoA
What is glucose needed by?
- brain
- gonads
- RBC
How are glucose levels maintained between meals?
glucose levels maintained between meals first by glycogen breakdown and then by gluconeogenesis
If glucose is too low in blood, then what happens
Use lipids for energy gives ketone body production in liver, these are energy sources (not acetone) but cause lowering of pH (ketoacidosis- metabolic acidosis)
If glucose is too high in the blood, what happens?
Glucose lost into urine, if too high it overcomes resorptive capacity of kidney - this carries water and electrolytes with it. (osmotic diuresis)- dehydration
What does long term raised blood sugar induce?
metabolic changes in many cells especially endothelia increased and abnormal ECM (fibrosis and glycation) and deposition of cholesterol causes
What does the deposition of cholesterol cause?
- vascular disease
- heart attack
- renal fibrosis
- retinal degeneration
- peripheral vascular loss
What was insulin isolated by?
Banting and Best, 1922
What does insulin induce?
- formation of glycogen or (when stores in liver and muscle full) fat
- induces uptake of amino acids, formation of proteins and inhibits their breakdown
What does insulin control?
Insulin controls glucose levels, regulating carbohydrate metabolism—but loss leads to abnormal use of fats –> acidosis, atherosclerosis and use of proteins and hence wasting
What is insulin formed by?
What is insulin degraded by?
Formed from: Beta cells in islet of langerhans
Degraded by: serum insulinase especially in liver
What is glucose monitored by?
What does it express?
Glucose is monitored by beta cells
express GLUT2 transporters (not insulin dependent)
What increases insulin secretion?
- Increased blood glucose
- Increased blood free fatty acids
- Increased blood amino acids
- Gastrointestinal hormones (gastrin, cholecystokinin, secretin)
- Glucagon, growth hormone, cortisol (all increase blood glucose- insulin induces uptake)
What do high levels of glucose lead to?
increased ATP formation which closes the ATP gates K+ channels
- cellular depolarisation as Na+ still enters cell and opening of Ca2+ channels
Exocytosis of insulin containing vacuoles
What decreases insulin secretion?
- Decreased blood glucose (fasting)
- Alpha-adrenergic activity (acute stress- low insulin saves uptake for CNS)
Tell me about Class 1 RTKs?
(receptor tyrosine kinases)
They come together on ligand binding
Tell me about class 2 RTKs?
Disulphide linked tetramers, remain together continually
Tell me about the Insulin receptor structure?
Has two alpha and beta subunits which are disulphide linked into alpa2beta2 heterotetrametric
What do the extracellular alpha subunits of the insulin receptor contain?
The insulin binding domains
What do the transmembrane beta insulin receptors contain?
The tyrosine kinase domains
The auto/cross phosphorylation of the beta subunits of insulin receptors induces what?
The docking of downstream signalling proteins
Ligand binding does not cause class 2 RTKs to dimeriza but what does it do?
It brings the two beta subunits closer to phosphorylate each other
What are the effects of insulin signalling?
- very rapidly induces fusion of intracellular vacuoles with the cell surface, these carry the insulin dependent glucose transporter-facilitated transfer of glucose
- activation of intracellular enzymes needed for glycogen production (slower)
increase in gene expression (slowest)
the induced fusion of intracellular vacuoles with the cell surface, carry insulin dependent glucose transporters.
What are these cell membranes permeable to?
These occurs in what cell types?
- permeable to amino acids (AA transporters also in these vacuoles)
- Occurs most in; RBCs, neurons, Beta-pancreatic cells
(have non-insulin dependent glucose transporters need glucose all the time)
The transfer of glucose and AA transporters to the plasma membrane
What uptake does insulin induce?
What happens to it?
Insulin induces glucose uptake, it is used or stored either as glycogen or lipid
What do carbohydrates induce?
glycogen storage in muscle and liver after a meal
formation of carbs. activates hepatic glucokinase, what does this trap?
absorbed glucose within the cell
When glycogen is made from carbs. what is maintained?
active glycogen synthetase
What keeps glycogen?
inactivates hepatic glycogen phosphorylase
What do carbs. promote?
The conversion of excess glucose to fatty acids ?
What do carbs. inhibit?
gluconeogenesis
Whats happens overall from carbs?
glucose is preferentially used after a meal- as preferential energy source or store
What does insulin promote?
fat synthesis and storage
In the liver, what does lipid formation promote?
- promotes glucose use -so saves lipids breakdown
- excess glucose uptake in liver converted to acetyl CoA used to form fatty acids.
- liver fatty acids released as triglycerides (VLDL) to be reabsorbed by adipocytes
what do lipids in adipocytes inhibit?
inhibits hormone (catecholamine) sensitive lipase (lowers lipid breakdown)
What happens overall when lipids are formed?
Overall - Lowered use of lipids to provide energy and increase in their formation
What does insulin promote is proteins?
- protein formation and storage
- uptake of AA into cells
What do proteins increase?
Increases gene transcription/ translation (especially genes promoting lipid and carbohydrate formation)
What do proteins inhibit?
Inhibits protein catabolism/ gluconeogenesis
How does insulin increase growth in proteins?
insulin works synergistically with growth hormone to increase growth
What happens overall with proteins?
Overall – increased protein production, reduced breakdown— growth
What are the actions of insulin?
What is glucagon produced by and what does it induce?
Produced by alpha cells
induces glycaemia (increased blood sugar levels)
When is glucagon released?
Release is caused by low blood glucose (initiated at < 80-90mg/glucose/ 100ml blood)
What does low blood sugar in alpha cells lead to?
low blood glucose leads to low ATP in alpha cells - ATP depended K channels close
- leads to depolarisation- and opening of voltage gated Na channel
- results in further depolarisation and voltage gated Ca channels opening
- allowing vesicle fusion and glucagon release
The following diagram shows the signalling pathway in the liver
Highly amplified system 5-10micrograms glucagon can double blood glucose in minutes
What does glycogenolysis in the liver increase?
Glycogenolysis in liver increasing blood glucose (opposing insulin)
What does the presence of glucagon cause?
Causes gluconeogenesis, liver forming glucose from amino acids (opposing insulin)
What does glucagon increase in the liver?
What are the amino acids in insulin and glucagon used for?
Increases amino acid uptake by the liver (like insulin). But …
insulin– amino acids used for growth
glucagon– amino acids used for energy
Does raised blood sugar after a meal inhibit or stimulate glucagon expression?
Raised blood sugar after a meal inhibits glucagon expression- and vice versa
Very high serum amino acids increases what?
Very high serum amino acids, increases glucagon expression
after a very high protein meal acts to increase uptake and convert amino acids to glucose (job is to maintain glucose levels)
Does exercise increase or decrease levels of glucagon?
why?
Exercise increases levels glucagon (in preparation for glucose debt)
In diabetes, what is there a failure of?
A failure in water reabsorption in the kidneys collecting duct
An excess of glucose in blood leads to what?
Osmotic diuresis
What does insipidus mean?
without taste
What does mellitus mean?
What does it lead to?
Means sweet taste
causes:
- adrenal diabetes
- insulin failure
What does adrenal diabetes cause?
Cushing’s disease
High glucocorticoids causes raised blood glucose
- Pregnancy- Gestational Diabetes (see later- also high glucocorticoids)
Diabetes mellitus is an insulin signalling failure
What are the two forms of diabetes?
What causes each?
Type 1 (insulin-dependent)
- a lack of insulin secretion
- combination of genetic and environmental factors
- normally an autoimmune disease
Type 2 (non-insulin-dependent)
- failure to respond to insulin “insulin resistant”
- reduced response when receive insulin
- long term raised blood glucose due to diet and insulin signalling pathway has turned off because of this
The results of diabetes is a lack of utilisation of glucose by all cells except what?
What does this result in?
neurones and RBCs
This results in overutilization of lipids and Proteins i.e. metabolically acting as if starving but not
Who is type 1 and type 2 diabetes usually found in?
Type 1-
- caused by auto-immune attack upon beta cells
- often occurs rapidly in teenagers
Type 2
- increased insulin levels observed with high energy diets, resulting in progressive loss of response to the hormone.
- Typically, in middle aged obese “metabolic syndrome”-a slow onset syndrome obese, insulin resistance, hyperglycaemia,->hypertension
What are the signs of diabetes ?
- High blood glucose
- Urine contains glucose-(seen when blood glucose is over 180mg/100mls blood)
- osmotic diuresis- polyuria- dehydration àincreased thirst
- ketone bodies are osmotically active which makes dehydration worse
- Use of proteins and lipids as metabolic fuels as glucose and AAs not taken in cells
What can diabetes lead to?
- increased appetitie
- wasting
- metabolic acidosis: as lipid converted to ketone bodies (acetone breath)
- Fibrosis: due to long term hypoglycaemia and changes in endothelial cell ECM caused by glycation
- neuropathy
- hypertension
- atherosclerosis- CV disease
What are the incidences of type 1 and type 2 diabetes?
Type1
1-30 new cases 100,000 per year (highest is Scandinavia?)
Type 2
UK 3,800,000 – i.e. about 1 in 20 diagnosed – true number is believed to be twice that a minimum of 10%
