export_endocrinology Flashcards
What factors stimulate insulin secretion?
- plasma aa
- GI hormones (CCK, gastrin etc) feed forward effect
- psymp activity
What % of insulin secretion is due to ‘feed forward;’effect
80%
Name 4 catabolc hormones
- glucagon
- GH
- cortisol
- catecholamines
What effect does insulin have?
increased:
- glucose oxidation
- lipogenesis
- glycogensis
- protein synthesis
What does glucagon do?
Increases:
- gluconeogenesis
- glycogenolysis
- ketogenesis
What glucose transporter is req in skeletal muscle?
GLUT 4
What is adipocytes response to insulin?
insert GLUT4 trans into membrane
What is glucose transformed to in the cell?
G-6-P
Glycogen
Fat
What glucose transporter ispresent in the liver?
GLUT 2
what does insulin stimulate in the hepatocyte?
hexokinase which converts –> G6P
Why is constant blood glucose vital for neurone?
they cannot regulate amount of glucose in CSF and the transport of glucose in/out is steady.
If CSF = plasma and glucose v high - dehydrate; if v low - starve
Are neurones sensitive to insulin?
NO
What efect does insulin have on K+?
inc K+ uptake into cells by providing ATP. It activates NaKATPase pump
What type of insulin is identical to dogs?
Pigs
What is cow insulin similar to?
Cats
How does insuln react with cells?
Binds to tyrosine kinase receptor
Where is insulin metabolised?
Liver and kidney
Which species often metabolises insulin fastest?
cats
What is crystalline zinc insulin?
recomb DNA
phosphate buffer
VERY RAPID ACTION
What is lente insulin?
insoluble - in acetate
No protamine
What type of insulin is found in canisulin
Lente insulin
What is the purpose of protamine zinc insulin?
Slow absorption and action. Large zinc crystals
What is insulin glargine?
v large precipitate. human. pos in cats.
From fastest to slowest name insulin formulations
- soluble
- semilente
- isophane
- lente
- protamine zinc
- glargine
What lifestyle factor need careful control in diabetic patients?
diet
State 2 pos adverse effects of insulin tx?
- hypoglycaemia
- insulin resistance
- antibodies attack exo insulin
- stress response (inc cortisol etc)
- receptor desensitisation/down-reg
Tx for OD of insulin?
feed
IV glucose
glucagon
What is Glipizide?
stim insulin secretion. Pos OD –> hypoglycaemia BUT less severe than insulin OD
What is Metformin?
decrease glucose absorption in GIT and dec liver glucose output and increase receptor sensitivity
How does glucose stimulate B-cells to secrete insulin?
- glucose uptake by GLUT2
- ATP prod
- BLOCK K+ channels which depol vgated Ca++
- Ca++ influx
- Insulin released
What is an insulinoma?
functional tumour, over-prod insulin.
Name a drug t treat hypERinsulinism
DIAZOXIDE
- activate K+channels and therefore Ca++ channels = no insulin!
Why is a clinical sign of diabetes 1PU/2PD?
++b glucose –> renal threshold. osmotic diuresis and glucose lost in urine (glycosuria).
- ## thirst centre, ADH etc..
What other effect can the loss of glucose in urine casue?
bdown of fat and protein –> ketone bodies
What is the Kreb cycle?
acetyl coA, product of FA and glucose catabolism is recyled and ATP made.
How are ketones formed?
XS acetyl coA.
if other parts of Kreb cycle are used for glucose production (oxaloacetate)
What is the main contributor of acetyl coA in starvation?
B-oxidation of Fats
Which type of thyroid hormone is most active?
T3 (free)
Name 5 functions of Thyroid hormones?
- Stim GH secretions
- Inc BMR
- CV stim
- Inc CHO use/lipolysis
- Inc milk prod
What are the signs of hypOthyroidism?
- Kg-gain, same appetite
- cold
- excercise intol
- alopecia (hair growth phase NOT activated)
- bradycardia
- dullness
- inc cholesterol
What % of T3 is from T4 metab?
80%
What parameters can be measured to detect thyroid disease?
- FT3/ 4 or TT3/4 4 is prefered
- endo TSH
- TSH stim
- Thyroglobulin Ab
Describe the TSH stim test?
basal T4, inj TSH and repeat. Normal = 1.5x increase in T4
What causes sick euthyroid syndrome
concurrent illness, supressing T4
What type of TH is Levothyroxine?
T4
What type of TH is Liothyronine?
T3
During starvation (etc)how is T4 preserved/inactivated?
de-iodinated to rT3
Where is T4 converted to T3/rT3?
liver, muscle and kidney
What is the significance of amount of TBG and pharmocokinetics?
++ TBG = long half-life
Which has the lowest conc of TBG, cats or dogs?
Cats
Name signs of HypERthyroid?
- inc appetite but kg-loss
- tachycardia
- excitable/difficult to handle!
Name 2 ways for testing for hypERthyroidism?
- TT4 levels
2. T3 suppression
Desc the T3 supression test
record basal TT4
oral T3, 3d
normal = 50%+ dec in T4
What is the main 2 anti-thyroid agents?
Methimazole
radioactive Iodide
What is the role of Methimazole?
- inhibit synth of T3/4
- metab by liver p450 & conjugation w/ GLUCORONIDE (not in cats!)
- affects of ++TH will mask renal failure, Tx may ‘unmask’ it
HOw does Radioactive I work?
iodine vital in T3/4 synth; will destroy rI containing cells. Alt to thyroidectomy.
radioactive for 3wks
What is the consequence of low dietary iodine?
Cant make TH
TSH remains high, stimulating follicular growth! No ned fb = goitre.
What can prevent iodine uptake?
Brassicas
Decsribe the HPA axis
- Higher centers stim hypothalamic neurones to release ACTHRH
- hormone travels through 2 x cap beds ( portal system)
- endocrine cells release ACTH from ant pit
- Adrenal G releases g-cort or androgens
- long and short loop neg fb from cortex and ant pit
Name the layers of the adrenal cortex
- zona glomerulosa (m-cort)
- zone fasiculata (g-cort)
- zona reticularis (androgen)
What percentage of the adrenal gland = cortex?
90%
What is the base structure of steroids?
cholesterol
What part of steroid synthesis does ACTH act on?
- rate limiting step (chol –> pregnenolone )
* only stimulates production of g-cort and androgens!
Desc the mech of action of g-corticoids
- inc mRNA synth of R and enzymes needed in gluconeogenesis.
- dec synth of cytokines and Rs
Desc regulation of aldosterone release
- dec BP –> RAAS
- inc in K+
- ad cortex prod aldosterone
- Principle cells (coll duct)
- inc Na+ reabs and K+ secretion
What is the significance of cortisol fluctuation and circadian variation in animals?
SMALL
What is the main stimulus for CRH?
Stress:
- infection
- trauma
Signs of hypERadrenocorticism
- hyperglycaemia
- 1PU/2PD
- DI
- skin pigment
- cachexia
- pot belly
Why is skin pigment changes seen in hypERadrenocorticism?
Synth of ACTH from ACTHRH makes POMC. in other tissues POMC makes MSH which inc melanin prod and skin darkening
Decs the stress leukogram
neutrophilia
lymphocytopenia
eosinopenia
HyperAC can be iatrogenic or spontaneous. Name the 2 forms of spontaneous HyperAC?
- pit-dependant hyperAC
2. adrenal-dependant hyperAC
Descr PDH?
pit tumour = inc ACTH –> inc cortisol
Descr adreno-hyperAC
adrenal tumour = inc cortisol and therefore LOW ACTH (due to neg fback)
What is hyper-AC known as?
cushings
what is hypoAC known as?
addisons
What is primary hypoAC
atrophy(?) or ad cortex
defic in mineral and gluco-corticoids
ACTH +++
mineralo defic signs (acute)!
What is 2rd hypoAC
ACTH defic
impaire g-cort secretion
will LEAD to atrophy
mineralo- usually not affected!
Name 4 diag tests for AC disease
- ACTH stim
- ACTH endo measure
- Dexamethazone supression test
- urine cortisol measure (cort:creatinine)
Desc the ACTH stim test
- take basal cortisol, inj with ACTH
- cortisol (3om) after
- normal = compare to chart, should be normal stimulation
hypER (higher) and hypO (lower)
descr the dexamethazone test
basal cortisol, inj dex, new cortisol (5hrs)
suppression should be clear
steroids can be mineralocorticoid-like or g-corticoid-like. And this gives then 2 main properties, name them
anti-inflam AND/OR Na+ retaining
Name a short acting steroid with equal anti-inflam and Na+ retaining prop
Hydrocortisone and cortisone
Why is Fludrocortisone inportant?
Only pharm steroid which has ++++ Na+ retaining prop
mineralocorticoid effects
How long is T1/2 to be classed as intermediate acting?
12-36hrs
What is interesting about the properties of the long acting steroids?
ONLY has g-corticoid effects, but VV+++ strong!
Why should steroid be withdrawn slowly?
exog cortisol suppresses pit prod of ACTH = when exo removed, no endo replaces
Adverse effects of long-term c-steroid
poor healing
myopathy
osteoporosis
oedema
laminitis
abortion
Name 2 adrenal steroid inhib
- Mitotane
2. Trilostane
Descr the function of mitotane
cytotox to z. fasic and z. retic NOT z. glom!
What are the main side effects of mitotane?
long T1/2
hypo AC
V+D
= req supplementary steroids to balance!
What is the mech of action of Trilostane?
- steroid analogue
* inhib of enzyme involved in corticosteroid synth
Why is Trilostane CI in preg animals?
inhib prog synth..
What type of calcium in metab active?
ionised ca++
What makes up serum calcium, as measured?
ionised and p-bound
What are the effects of inc PTH?
- inc osteoclastic activity
- inc absorption (vitd3)
- inc renal reabs
How does VitD3 inc Ca++ absorption?
- 2 x hydroxylations (liv, kid)
- inc Ca++ binding protein synthesis
- t.f inc transport
What is the other name for Vit D3?
Calcitriol
Name 2 other forms of Vit D used pharmacologically
- Di-hydrotachysterol (DHT) - VitD2 analogue
* Alfacalcidol - active D3 metabolite; 1 x hydroxyl only however
What are the effects of calcitonin?
dec free Ca++; less important, dec osteoclasts
What are the effects of PTH on PO4 levels?
inc renal excretion
What are the effects of Vit D3 on PO4?
Same as on Ca++
What are the effects of g-corticoids on Ca++ metab?
Inc free Ca++ and inc osteoclasts
Sex steroid protect against _____
osteoporosis
How does Prolactin try and prevent parturient hypocalcaemia?
prolactin released at part –> milk prod
it stim Vit D3 synth
Vit D3 in Ca++ (free)
Name the 5 different calcium salt formulations
calcium. .
1. gluconate
- carbonate
- chloride
- lactate
- borogluconate
What are the drawbacks of oral calcium admin?
- fibre and phytases interfer with absorption
- Vitd3, PTH and
hwat is best treatment of a ‘downer cow’, with hypocalc
IV admin of calcium gluconate. Jug of milk v
Supplementation with Vit D3 and diet high in Ca++, is advised. What are Vit D adverse effects?
narrow Therap index
hypercalc
hyper phosph
nephrocalcinosis
Why would half life of Vit D3 be reduced in renal disease?
reduced vit d3 binding globulin
What cells detect need for EPO?
renal interstitial cells’ oxygen sensors
What disease state would anti-diuretics be for?
Diabetes insipidus
Why is desmopressin preferntial than vasopressin?
long DOA
no vaso-con effects
What are the actions of desmopressin?
binds and stim ADH receptors in coll duct
What is IGF-1
insulin like growth factor -1
What is unusual with release of GH?
regulated by a GHRH (releasing) and GHIH (inhibition)
What does IGF-1 do?
mediates action of GH in most tissues. Prod in liver.
Can GH deficits be treated?
no canine GH avail; bov/porcine only. a-bod will develop
