Endocrine Flashcards
Describe the pancreas anatomy.
-glandular organ in abdomen
-two lobes
>one behind stomach
>one prox to duodenum
Describe the exocrine VS endocrine pancreas.
- Exocrine
-acinar & duct cells
-secrete enzymes into duodenum
-involved in GI function (digestion)
-97% of pancreas - Endocrine
-4 types (organized in islets)
-secrete hormones into blood
-glu metabolism
-2-3% of pancreas
-sym & parasym
Describe the endocrine 4 types of islets.
- Alpha cell = glucagon
- Beta cell = insulin most
- Delta cell = somatostatin
- F cells = pancreatic polypeptide least
all hormones involved in glu metabolism & reg of blood glu levels
Describe protein/peptide hormones.
-insulin, ACTH, PTH, CCK, LH, FSH, TSH
-syn as lg molecule inside ER & GA = packaged into secretory granules
>pre prohormone -> prohormone -> hormone
-circulate in unbound in blood
>intact mol or active/inactive frag
>hydrophilic
-short half life
-bind to receptors in cell membrane
>hormone receptor complex activate internal second messenger
Describe insulin.
-polypeptide hormone made by beta cells in resp to hyperglycemia
-two peptide chains (alpha & beta) connected by disulfide bridges
-syn as preproinsulin within rER
-small peptide frag (signal seq) removed from ER to make proinsulin
-proinsulin -> GA -> processing -> packaged into granules -> broken insulin & connecting C peptide
Describe the diff in amino acid sequences between species.
-cattle, sheep, horses, dogs, whales differ in 8, 9, 10 of alpha chain
-porcine differs from human insulin by 1 AA
-bovine insulin differs from cat insulin by 1 AA
-porcine insulin differs from cat insulin by 3 AA
-human insulin differs from cat insulin by 4 AA
-porcine & canine insulin the same
*no feline specific insulin
*US/canada human & porcine insulin used from treating companion animals
Describe the factors affecting insulin release.
secretagogue = depends on natural diet & nutritional status of species
[substance that stim secretion of another substance]
1. Glu -> imp for omnivores
2. AA -> imp for carnivores
3. FA -> stim insulin release in humans
Describe GLUT2 glucose transporter.
insulin released from beta cells
-GLUT2 in membrane surface of beta cells
>allows glu to diffuse freely into cell
>extracellular fluid glu conc directly affects glu conc inside beta cells
-increase in blood glu conc = insulin secretion & production
hyperglycemia -> high ECF (glu)
sulfonylurea = hypoglycemic
Describe insulin release pattern.
biphasic kinetics
1. Acute phase
-release of preformed insulin
2. Chronic phase
-syn of insulin
Describe insulin receptors.
-after release = insulin binds to membrane receptor on target tissue
>insulin receptor tyrosine kinase = dimerize & phosphorylate
Describe the insulin net effect.
lower blood conc of glu, FA, AA by:
1. Promoting intracellular conversion of compounds to storage forms
-glu -> glycogen
-FA -> triglycerides
-AA -> proteins
2. Facilitate gly entry into cells
compound -> storage form = anabolic effect
Describe GLUT4 glu transporter.
-insulin facilitates glu entry into cells by increasing # of specific GLUT4 in cell membrane
*GLUT4 = only insulin sensitive
*muscle & fat need insulin to take glu into cells
Describe insulin action on muscle.
(Smooth, striated, cardiac m)
-stim glycogen syn enzymes
-promoting storage of glu molecules in form of glycogen
glycogenesis = store excess glu as glycogen for later use
-promote use of glu as fuel source
>reduce FA oxidation
>absence of insulin muscle rely on FA
-enhance AA uptake = promote muscle growth
Describe insulin action on adipose tissue.
-increase glu transport
>glycerol formation = combine w FA delivered to adipose tissue to form triglycerides
>FA come from VLDL made in liver
>glycogen syn
-insulin inhibits lipolysis
>promote adipose deposition
lipolysis = break down TAG into FA & glycerol
Describe the insulin action on liver.
-promote FA syn in hepatocytes
>stim FA & TAG into lipoprotein bound vesicles like VLDL for transport into adipocytes
-insulin stim glycogen syn (glycogenesis)
>decrease gluconeogenesis & glycogenolysis
*gluconeogenesis = makes glu from non carbohydrate substrates (AA, glycerol, lactate)
*glycogenolysis = breaking down glycogen into glu
Describe the physiological action of insulin.
Describe insulin inactivation.
-metabolized by liver & kidneys
>enzymes reduce disulfide bonds
>chains subjected to protease activity
—reduce them to peptides & AA
half life is 10 min
Describe counterregulatory hormones.
*hormones that counteract the effects of insulin
-glucagon
-EPI/NE
-cortisol
-GH
Describe glu homeostasis.
Describe glucagon.
-polypeptide hormone made in alpha cells
>29 AA
>close relationship w insulin
>homologous between species
>half life 6-7 min (endogenous)
Describe glucagon synthesis.
-stim by decreased glu conc
>levels decline below threshold (hypoglycemia)
-peptide hormone
-made as preprohormone -> prohormone -> cleaved in glucagon + diff sub products
-proglucagon expressed in tissue & cleaned into diff sub products other than glucagon
Describe glucagon secretion.
-glu enters cells via GLUT transporter
-glu gen ATP
-low glu = low intracellular ATP
-low ATP = close ATP sensitive K channels
-efflux of K reduced -> cell membrane changes
-opens voltage dependent Ca channels
-influx of Ca = trigger for exocytosis of glucagon
Describe glucagon mech of action.
Glucagon receptor = G-protein coupled receptor (GPCR):
1. Glucagon binds to liver cell membrane receptor
2. G-protein is activated
3. Adenylyl cyclase converts ATP to cAMP
4. cAMP initiates enzyme cascade
Describe glucagon target tissues.
- Liver
- Adipocytes
- Kidney, heart, brain, GIT
Describe glucagon - liver.
physiological action of glucagon = opposite of insulin
*main effect in liver & enhance availability of glu to other organs of the body
1. Decrease glycogen syn
>inhibition of glycogen synthase
2. Breakdown of liver glycogen
>activation of glycogen phosphorylase
3. Increase in liver gluconeogenesis
4. Decrease glu breakdown
Describe glucagon - adipose tissue.
Minor effect compared to liver (less receptors)
1. Promotes lipolysis
2. Increase FA available to tissues (energy source)
3. Supply glycerol to liver gluconeogenesis
Describe glucagon catabolic effect.
Describe glucagon x carnivores.
-glucagon not always opposing hormone to insulin
-protein ingestion stim both insulin & glucagon release
>AA = alanine & arginine
>imp in obligate carnivores
>insulin release in resp to increased AA levels -> lower glu conc
>glucagon promotes rapid conversion of AA to glu by stim gluconeogenesis
Describe EPI, cortisol, GH.
- Epi
-similar actions as glucagon
-glu for symp resp
-some diff - Cortisol
-covered in adrenal gland - GH
-similar action as glucagon
Describe pancreatic somatostatin.
-made by delta cells
>protein hormones
-inhibitory action
>decrease motility & secretory activity of GIT
>inhibits secretion of all endocrine types of islet
—glucagon more affected than insulin
Describe pancreatic polypeptide.
-made by F or PP cells
>secretion stim by GI hormones, vagal stim & protein ingestion
>inhibition thru somatostatin
-effects towards GIT
>decrease gut motility & gastric emptying
>inhibit secretion of pancreatic enzymes & contraction of gall bladder
Describe insulin deficiency.
- Lack/deficiency of insulin = Diabetes Mellitus
- Insulin deficiency (absolute or relative)
-absolute = absence of insulin = type 1 diabete s
-relative = insulin not working properly/insulin resistance = type 2 diabetes
Describe diabetes mellitus - signalment.
-middle aged to older
-predisposed to develop diabetes:
>intact F dogs & M cats
>breeds upon location
>patients w certain conditions like pancreatitis & adrenocortical hormone disorders like hyperadrenocorticism
Describe diabetes mellitus - hyperglycemia.
Insulin deficiency causes blood glu to increase
-glu uptake from insulin sensitive tissues compromised
Describe hyperglycemia state CS.
Describe diabetes mellitus - glucagon production.
-insulin directly inhibits glu release by binding to insulin receptor on alpha cells
-glucagon stim insulin secretion directly
>bind to receptor on beta cell
>stim indirectly thru induction of hyperglycemia by glycogenolysis & gluconeogenesis
Describe paradoxical hyperglucagonemia.
-beta cell deficiency + alpha cell insulin & somatostatin resistance = alpha cell dysfunction & loss of regulation of glucagon secretion = HYPERGLUCAGONEMIA
Describe hyperglucagonemia CS.
glucagon action on adipose tissue
-insulin deficiency = lipolysis of storage fat & release FFA
-enzyme: hormone sensitive lipase (HSL) activated
>hydrolysis of stored TAG
>release lg amounts of FFA & glycerol in blood
-excess FFA converted into phospholipids & cholestrol
-TAG formed at same time in liver
>increase in blood lipids expected
Describe how diabetes mellitus affects muscle.
-insulin deficiency = protein depletion & increased plasma AA
>catabolism of protein increases & protein syn stops
>AA in blood used as:
—direct energy source in liver
—substrate for gluconeogenesis
Describe type 1 diabetes mellitus.
permanent hypoinsulinemia
-absolute deficiency
>no increase in endogenous insulin after stim -> exogenous insulin maintain control of glycemia & avoid ketoacidosis to survive
-common in dogs
Describe the factors involved in ethiopathogenesis.
• Genetics
• Immune-mediated insulitis
• Pancreatitis
• Obesity
• Concurrent hormonal disease
• Drugs
• Infection
• Concurrent ilness
• Hyperlipidemia
Describe immune mediated insulitis.
-mononuclear infiltrate made of sm lymphocytes & monocytes = limited to islets
Describe the islet amyloidosis involved in etiopathogenesis.
-beta cell dysfunction
>healthy beta cell can adapt to obesity & insulin resistance by increasing insulin secretion
-amylin (islet amyloid polypeptide IAPP)
>polypeptide made by beta cells w insulin secretion
>increases satiety, decreases gastric empty & reduced glucagon production
-amyloidogenic AA structure w potential to form amyloid deposition in islets (amylin aggregates) = amyloidosis
deposition is toxic to beta cells = dysfunction
Describe obesity in type 2 diabetes mellitus in cats.
Describe what enhances syn of ketone bodies.
- Increased mobilization of FFA from TAG stored in adipose
- Shift in hepatic metabolism from fat synthesis to fat oxidation & ketogenesis
Describe DKA & dehydration.
• Hypovolemia
• Hemoconcentration
• Metabolic stress – more release of counterregulatory hormones
• Prerenal azotemia – hypovolemia → decreased blood flow to the kidneys
• Hyperviscosity
• Shock
• Aldosterone release – more potassium loss
• Catecholamine release – more catabolism
Describe the divisions of the adrenal gland.
- Cortex
-mesodermal
-3 layers/zones
>zona glomerulosa = mineralocorticoids
>zona fasciculata = glucocorticoids
>zona reticularis = androgens - Medulla
-ectodermal
>catecholamines
Describe the HPA axis.
Describe steroid hormone synthesis.
- Adrenal cortex makes steroid hormone
-hormones derived from cholesterol - Cholesterol used to make pregneolone
-common to all adrenocortical hormones
-occurs in mitochondria
-regulated by ACTH
>limits the rate of syn of all adrenocortical hormones
*diff tissues of adrenal gland express diff enzymes = not all processes occur in all cells
Describe steroid hormone receptors.
-bind to intracellular receptors
-located in cytosol or nucleus
>cytoplasmic receptors translocate to nucleus after hormone binding
-hormones bind to their respective intracellular receptor & alter ability of proteins to control transcription of specific genes
-overlap between glucocorticoids & mineralocorticoids
Describe zona glomerulosa - aldosterone regulation.
-production regulated by RAAS
-stimuli for aldosterone secretion (detected by cells of macula densa)
>decrease in ECF vol
>decrease in plasma Na conc
-potassium = regulatory factor for mineralocorticoid secretion
>increase in K stim directly zona glomerulosa (independent of RAAS)
Describe zona fasciculata cortisol & stress.
-biological resp to external or internal stimuli or body resp to chain to maintain homeostasis
>hypoglycemia, physical trauma, inflammation, pathogenic, disease
*glucocorticoids, stress, diurnal rhythm influence axis
Describe cortisol lipid metabolism.
-increase mobilization of FA from adipose
-shift metabolism from glu to fat utilization
-enhance oxidation of FFA in cells
>reduced glu transport into fat cells
-cause obesity
-depletion peripheral fat while increasing visceral (abdominal) fat
Describe zona reticularis - androgens.
-androgens are hormones that interact w male sex hormone receptors
-dehydroepiandrosterone (DHEA) converted to DHEA-sulfate (sulfotransferase)
-DHEA converted to androstenedione released into blood stream & taken up by testis or ovaries to make testosterone & estrogens
-not very active compared to testosterone
-converted in testosterone or estrogen in other tissues
-adrenal androgens action not significant
Describe adrenal medulla - catecholamines.
-chromaffin cells = neuroendocrine cells are modified post gang sym neurons (lack dendrites & axons)
>stim by AcH from pre gang sym neurons that bind w nicotinic receptors on chromaffin cells
>neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) = required for stress induced catecholamine secretion
-produce & secrete
>EPI (hormone 80%)
>NE (neurotransmitter & hormone 20%)
>dopamine (trace)
Describe adrenal medulla - stimulation.
- Unstressed = synaptically released AcH activates chromaffin cells
- Stressed = increase in splanchnic nerve electrical discharge & increase in secretion of catecholamines
>increased # of nerve fibers innervating medulla
>switch from cholinergic to noncholinergic neurotransmission (ex. PACAP)
Describe adrenal medulla - synthesis.
-syn inside cell begin w conversion of tyrosine to DOPA by enzyme tyrosine hydroxylase
-end products of tyrosine metabolism include DOPA, dopamine, EPI, & NE
>dopa converted to dopamine in cytosol
>dopamine converted to NE w chromaffin granules = dopamine beta hydroxylase
>in cells that secrete EPI, NE returns to cytosol where its converted to EPI
>EPI moves to granules for storage before release
Describe catecholamines actions.
- EPI & NE
-increase energy availability & metabolism - Bind to adrenoceptors that are cell surface GPCRs on target tissues
*major types of adrenergic receptors
>alpha, alpha1, alpha 2
>beta, beta1, beta2
Describe hyper adrenocorticism.
*over secretion of cortisol
CUSHINGS DISEASE
1. Primary = adrenal gland tumor (20%)
2. Secondary = pituitary gland tumor (80-85%)
>tumor secreted ACTH -> stim overproduction of cortisol
*common in dogs
Describe hyperadrenocorticism - primary.
Describe hyperadrenocorticism - secondary.
Describe hyperadrenocorticism - CS.
Describe the thyroid gland.
- thyroid follicles = where thyroid hormones syn
>composed of follicular cells arranged in circular pattern
—single layer of epi
—cells resp for thyroid hormone syn
>follicles filled w colloid
—intrafollicular fluid rich in thyroglobulin
—storage of thyroid hormones - Parafollicular cells (C cells)
-between thyroid follicles & make hormone calcitonin
>calcium regulation
Describe the two molecules that serve as precursors/raw materials.
- Tyrosine (amino acid)
- Iodide
Describe Iodide.
-obtained from diet as Iodine & taken up from blood to thyroid epi cells
-iodine converted to iodide in intestinal tract
-follicle cells uptake iodide thru active transport
>Na/I cotransporter (Na is driving force to bring I into cell)
>intracellular Iodide conc higher than outside of cell
Describe thyroid peroxidase (TPO) action.
- Oxidation of iodide ion to iodine (I2)
-via thyroid peroxidase (TPO) located in apical membrane
-iodine can then combine w tyrosine - Binding of iodine w thyroglobulin molecule
-‘organification of the thyroglobulin’
-TPO
>provides iodine at point in cell where thyroglobulin is released
>iodine can then combine w tyrosine
*tyrosyl ring can accommodate 2 iodine mol (MIT or DIT) [mono or di] - TPO catalyses the fusion of 2 of iodinated thyrosines
-1 DIT + 1 DIT = T4 or thyroxine (4 iodine molecules)
-1 MIT + 1 DIT = T3 or triiodothyronine (3 iodine molecules)
>depending on position of iodine, reverse T3 can be formed = inactive
Describe TPO summary.
- Iodide is oxidized to iodine
- Iodination of tyrosine on thyroglobulin ‘organification of iodide’
- Catalysis of MIT & DIT to make triiodothyronine (T3) & thyroxine (T4) coupling
Describe thyroid hormone - secretion.
-follicular (epi) cells ingest (endocytosis) thyroglobulin w attached thyroid hormone (T4 & T4), DIT, MIT
>endosomes fuse w lysosomes
-hydrolytic enzymes digest thyroglobulin
>T3 & T4 released
-free thyroid hormones diffuse out of epi cells -> interstitial space -> blood
-thyroglobulin & I- -> recycled
Describe thyroid hormones - regulation.
*hypothalamus-pituitary-thyroid-axis
-hypothalamus makes thyrotropin releasing hormone (TRH)
-pituitary makes thyroid stimulating hormone (TSH)
-thyroid stim by TSH to make T3 & T4
Describe thyroid hormone - actions.
-primary factors for control of metabolism
-bind to nuclear receptors & initiates the transcription of mRNA
-increase BMR = stim carbohydrate & fat metabolism
