Endocrine Flashcards
(106 cards)
1
Q
Describe the pancreas anatomy.
A
-glandular organ in abdomen
-two lobes
>one behind stomach
>one prox to duodenum
2
Q
Describe the exocrine VS endocrine pancreas.
A
- 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
3
Q
Describe the endocrine 4 types of islets.
A
- 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
4
Q
Describe protein/peptide hormones.
A
-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
5
Q
Describe insulin.
A
-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
6
Q
Describe the diff in amino acid sequences between species.
A
-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
7
Q
Describe the factors affecting insulin release.
A
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
8
Q
Describe GLUT2 glucose transporter.
A
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
9
Q
Describe insulin release pattern.
A
biphasic kinetics
1. Acute phase
-release of preformed insulin
2. Chronic phase
-syn of insulin
10
Q
Describe insulin receptors.
A
-after release = insulin binds to membrane receptor on target tissue
>insulin receptor tyrosine kinase = dimerize & phosphorylate
11
Q
Describe the insulin net effect.
A
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
12
Q
Describe GLUT4 glu transporter.
A
-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
13
Q
Describe insulin action on muscle.
A
(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
14
Q
Describe insulin action on adipose tissue.
A
-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
15
Q
Describe the insulin action on liver.
A
-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
16
Q
Describe the physiological action of insulin.
A
17
Q
Describe insulin inactivation.
A
-metabolized by liver & kidneys
>enzymes reduce disulfide bonds
>chains subjected to protease activity
—reduce them to peptides & AA
half life is 10 min
18
Q
Describe counterregulatory hormones.
A
*hormones that counteract the effects of insulin
-glucagon
-EPI/NE
-cortisol
-GH
19
Q
Describe glu homeostasis.
A
20
Q
Describe glucagon.
A
-polypeptide hormone made in alpha cells
>29 AA
>close relationship w insulin
>homologous between species
>half life 6-7 min (endogenous)
21
Q
Describe glucagon synthesis.
A
-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
22
Q
Describe glucagon secretion.
A
-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
23
Q
Describe glucagon mech of action.
A
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
24
Q
Describe glucagon target tissues.
A
- Liver
- Adipocytes
- Kidney, heart, brain, GIT
25
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
26
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
27
Describe glucagon catabolic effect.
28
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
29
Describe EPI, cortisol, GH.
1. Epi
-similar actions as glucagon
-glu for symp resp
-some diff
2. Cortisol
-covered in adrenal gland
3. GH
-similar action as glucagon
30
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
31
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
32
Describe insulin deficiency.
1. Lack/deficiency of insulin = Diabetes Mellitus
2. Insulin deficiency (absolute or relative)
-absolute = absence of insulin = type 1 diabete s
-relative = insulin not working properly/insulin resistance = type 2 diabetes
33
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
34
Describe diabetes mellitus - hyperglycemia.
Insulin deficiency causes blood glu to increase
-glu uptake from insulin sensitive tissues compromised
35
Describe hyperglycemia state CS.
36
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
37
Describe paradoxical hyperglucagonemia.
-beta cell deficiency + alpha cell insulin & somatostatin resistance = alpha cell dysfunction & loss of regulation of glucagon secretion = HYPERGLUCAGONEMIA
38
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
39
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
40
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
41
Describe the factors involved in ethiopathogenesis.
• Genetics
• Immune-mediated insulitis
• Pancreatitis
• Obesity
• Concurrent hormonal disease
• Drugs
• Infection
• Concurrent ilness
• Hyperlipidemia
42
Describe immune mediated insulitis.
-mononuclear infiltrate made of sm lymphocytes & monocytes = limited to islets
43
Describe cataracts.
-long term complication
-altered osmotic relation in lens induced by accumulation of sorbitol & galactitol
>sugar alcohols made in reduction of glu & galactose by enzyme aldose reductase in lens
>hydrophilic agents causing influx of water = swelling & rupture of lens fibers
44
Describe type 2 diabetes mellitus.
*resistance to metabolic effects of insulin*
-relative deficiency
>impaired insulin in liver, muscle, adipose tissue (resistance) & beta cell failure
-common in cats
45
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*
46
Describe obesity in type 2 diabetes mellitus in cats.
47
Describe clinical remission.
-CS disappear, blood glu conc normalizes & insulin treatment or anti diabetic drug = discontinue
-depend on beta cell dysfunction
>irreversible damage = amyloidosis
>reversible damage = glucotoxicity
48
Describe diabetic neuropathy.
-hyperglycemia -> nerve injury
>schwann cells & axons of myelinated fibers
>micro vascular abnormalities
CS:
• Limb weakness
• Difficulty to jump
• Base-narrow gait
• Ataxia
• Muscle atrophy in pelvic limbs
• Plantigrade posture
• May progress to front limb
• Postural reaction deficits
• Decreased tendon reflexes
• Irritability when feet are touched
49
Describe hormone levels in DM.
1. Circulating levels elevated in diabetes mellitus (esp type 1)
-promote insulin resistance
-stim lipolysis & gen of FFAs
-shift hepatic metabolism to fat oxidation & ketogenesis
-worsen hyperglycemia & ketonemia -> acidosis -> fluid depletion & hypotension
50
Describe counterregulatory hormones in diabetic ketoacidosis.
1. Glucagon = most influential ketogenic hormone
-EPI stim thru stim of lipolysis
2. Glucagon & EPI = insulin resistance
-inhibiting insulin mediated glu uptake in muscle
-stim hepatic glu prod thru glycogenolysis & gluconeogenesis
3. Cortisol & GH
-enhance lipolysis in presence of insulin deficiency
-block insulin action in peripheral tissues
-potentiate the stim effect of glucagon & EPI on hepatic glu output
51
Describe ketone bodies.
-derived from oxidation of FFA by liver
-used as energy source during glu deficiency
-excessive production = ketosis & ketoacidosis
*oxidation of FFA = acetoacetate
*NADH -> acetoacetate is reduced to B hydroxybutyrate
*decarboxylation of acetoacetate -> acetone
52
Describe what enhances syn of ketone bodies.
1. Increased mobilization of FFA from TAG stored in adipose
2. Shift in hepatic metabolism from fat synthesis to fat oxidation & ketogenesis
53
Describe acid base status in diabetic ketoacidosis.
-ketones = strong acids
-excess ketones = acidosis (increase in H)
-failure of kidney to compensate in DKA is a result of B hydroxybutyrate & acetoacetate
>renal threshold is low - amount exceed the kidney capacity
>loss of water & electrolytes
>excreted as sodium & potassium
>loss of bicarb
54
Describe electrolyte abnormalities - sodium.
1. Osmotic diuresis = excessive urinary loss -> reduced sodium absorption
2. Hyperglycemia = water shift out of intracellular to extracellular
3. Insulinopenia = reduced renal absorption of insulin - insulin enhance renal sodium reabsorption in distal portion of nephron
4. Vomiting & diarrhea
55
Describe electrolyte abnormality - potassium.
1. Redistribution of K from intracellular to ECF
-entry of K into cells impaired in insulinopenia
-shift of K out of cells = enhanced by acidosis & breakdown of intracellular protein secondary to insulin deficiency
2. During treatment shift of K from ECF to ICF
-shift hypokalemia = caused by exogenous insulin
3. Renal loss of K
-osmotic diuresis causes urinary loss of K - secondary hyperaldosteronism augment the K deficit
-hypomagnesemia causes renal outer medullary K channel to secrete more K
4. GI loss of K due to malabsorption syndrome
-diabetic induced motility disorder, bacterial overgrowth, diarrhea
56
Describe electrolyte abnormality - phosphate.
1. Renal loss of phos
-phos & K shift from intracellular to ECF resp to hyperglycemia & hyperosmolality
-osmotic diuresis
-reduced renal phos absorption - acidosis & hyperglycemia cause reduction of absorption by Na-Pi transporters in renal prox tubule
57
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
58
Describe DKA.
-hyperglycemia
-metabolic acidosis
-ketosis
-hyperventilation/seizure
59
Describe how you monitor ketones in practice.
1. Acetoacetate = urine dipstick
2. B hydroxybutyrate = blood
60
Describe insulinoma.
-pancreatic tumors of pancreatic beta cells
-occurs in dogs, ferrets (rare in cats)
-neoplastic beta cells syn & secrete insulin independent of normal suppressive effect of hypoglycemia
-life threatening periods of hypoglycemia
*brains only source of energy is glu
61
Describe glucagonoma.
-neoplasm of alpha cells
-insulin resistance -> diabetes mellitus
-weight loss
-superficial necrolytic dermatitis
62
Describe the divisions of the adrenal gland.
1. Cortex
-mesodermal
-3 layers/zones
>zona glomerulosa = mineralocorticoids
>zona fasciculata = glucocorticoids
>zona reticularis = androgens
2. Medulla
-ectodermal
>catecholamines
63
Describe the HPA axis.
64
Describe steroid hormone synthesis.
1. Adrenal cortex makes steroid hormone
-hormones derived from cholesterol
2. 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
65
Describe steroid hormone transport.
*carried in plasma w specific binding globulins
*corticosteroid binding globulin (CBG) or transcortin
1. Cortisol transport
-75% bound to transcortin
-15% bound to albumin
-10% unbound
2. Aldosterone transport
-10% bound to transcortin
-50% bound to albumin
-40% unbound
66
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
67
Describe steroid hormone metabolism (elimination).
1. Metabolism involves liver
-modification of hormones for secretion
-conjugation w sulfates & glucuronides reduces biological potency
-water soluble for passage in urine
2. Half life
-cortisol = 1 hr
-aldosterone = 20 min
68
Describe zona glomerulosa - mineralocorticoids.
1. Mineralocorticoids = corticosteroids that influence salt & water balances (electrolyte/fluid balance)
2. Aldosterone = primary mineralocorticoid
3. Acts on distal tubules in kidneys to make:
A) active reabsorption of Na
-principle cells (CD) = increasing activity of epithelial Na channels (ENaC) & syn of sodium potassium pump (Na/K/ATPase)
B) active secretion of K
-principle cells = thru BK & renal outer medullary potassium channel (ROMK)
C) active secretion of protons
D) passive reabsorption of water
69
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)
70
Describe zona fasciculata - cortisol.
-regulation via hypothalamic (CRH), pituitary (ACTH), adrenal (cortisol) axis (HPA) in resp to low blood glu & other stressors = stress hormone
-cortisol increases the expression of genes that will regulate: metabolism, immune system, cardiovascular function, growth, reproduction
-circadian or diurnal rhythm -> high blood conc in morning than evening
71
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
72
Describe cortisol carbohydrate metabolism.
-stim syn of enzymes involved in gluconeogenesis & glycogenolysis
-mobilize substrate from muscle & fat
-antagonizes insulin effect
>insulin inhibits gluconeogenesis in liver
>decrease glu utilization by peripheral cells
*brain unaffected
-potentiates action of glucagon & EPI on glucose metabolism
-can cause DM
>increased gluconeogenesis + reduction in glu utilization
>20% dogs w HAC develop DM
73
Describe cortisol protein metabolism.
1. Stim catabolism of proteins in muscle
*mobilization of AA from the extrahepatic tissues
-serves as substrate for enzyme manufacturing
-serves as substrate for gluconeogenesis
2. Decrease insulin sensitivity
-decrease glu uptake
-decrease glycogen syn
74
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
75
Describe cortisol immune system.
1. Immune system suppressant & anti inflammatory
-decrease formation of prostaglandins & leukotrienes production
-reduce secretion of histamine by mast cells
-decrease phagocytosis & suppress antibody formation
*SUMMARY:
-downreg pro inflammatory factors
-upreg anti inflammatory factors
*inhibits inflammation
76
Describe cortisol other effects.
1. CVS
-increases sensitivity of vascular smooth muscle to vasoconstrictors
>catecholamines
-suppress the release of vasodilatorys
>NO
-maintain BP
2. Cortisol inhibit secondary secondary functions not needed for survival
-reproductive system: various mech of action -> reduce repro success
-growth: various mech of action
77
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
78
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)
79
Describe adrenal medulla - stimulation.
1. Unstressed = synaptically released AcH activates chromaffin cells
2. 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)
80
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
81
Describe catecholamines actions.
1. EPI & NE
-increase energy availability & metabolism
2. Bind to adrenoceptors that are cell surface GPCRs on target tissues
*major types of adrenergic receptors
>alpha, alpha1, alpha 2
>beta, beta1, beta2
82
Describe catecholamines metabolism (elimination).
-half life in circ about 2 min for NE & less for EPI
-liver & kidney metabolism
>degraded by methylation by catechol-O-methyltransferases (COMT)
-excreted in urine
83
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
84
Describe hyperadrenocorticism - primary.
85
Describe hyperadrenocorticism - secondary.
86
Describe hyperadrenocorticism - CS.
87
If you give a low dose of dexamethasone (glucocorticoid) what will occur in a normal VS HAC dog?
1. Normal dog
-when levels of glucocorticoids increase -> neg feedback mechanism activated:
>reduce amount of CRH made by hypothalamus
>reduce amount of ACTH made by anterior pituitary gland
2. HAC dog
-primary HAC: adrenal gland cont to make cortisol w/o interruption (lack of suppression of cortisol conc)
-secondary HAC: pituitary gland cont to make ACTH & not resp to increased glucocorticoids (lack of suppression of cortisol conc)
88
Describe hypoadrenocorticism.
-deficiency of cortisol (glucocorticoid) &/or aldosterone (mineralcorticoid) = Addison disease
-common in young/middle aged dogs/horses
-deficiency can be result of dysfunctional adrenal gland (primary) or pituitary gland (secondary)
89
Describe primary VS secondary hypoadrenocorticism.
1. Primary (adrenal)
-endogenous plasma ACTH increased due to lack of neg feedback
-reduced resp to exogenous ACTH
2. Secondary (pituitary)
-endogenous ACTH decreased
-may/may not be a reduced resp exogenous ACTH
90
Describe hyperaldosteronism.
*over secretion of aldosterone = conns syndrome
-older cats & dogs
-hypersecreting adrenal tumor or bilateral adrenal hyperplasia
-electrolyte changes
>hypokalemia
>hypernatremia
>metabolic alkalosis
-diagnosis
>increased plasma aldosterone
>low plasma renin
-ultrasonographic imaging
>unilateral/bilateral adrenal hyperplasia/enlargement
-treatment
>K supplement
>removal of adrenal tumor
91
Describe pheochromocytoma.
-catecholamine producing neuroendocrine tumors from chromaffin cells of adrenal medulla or sym paraganglia
-signs absent/sporadic:
>hypertension, blindness, collapse, tachycardia, arrythmia
92
Describe the thyroid gland.
1. 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
2. Parafollicular cells (C cells)
-between thyroid follicles & make hormone calcitonin
>calcium regulation
93
Describe the two molecules that serve as precursors/raw materials.
1. Tyrosine (amino acid)
2. Iodide
94
Describe tyrosine.
-part of thyroglobulin
>syn by follicular (epi) cells
>secreted into follicle lumen or colloid
95
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
96
Describe thyroid peroxidase (TPO) action.
1. Oxidation of iodide ion to iodine (I2)
-via thyroid peroxidase (TPO) located in apical membrane
-iodine can then combine w tyrosine
2. 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]
3. 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
97
Describe TPO summary.
1. Iodide is oxidized to iodine
2. Iodination of tyrosine on thyroglobulin ‘organification of iodide’
3. Catalysis of MIT & DIT to make triiodothyronine (T3) & thyroxine (T4) *coupling*
98
Describe T4 & T3.
-T4 is the major hormone (90%) made by follicular cells
>small amounts of T3 made (30%)
>major source of T3 is peripheral deiodination of T4
-thyroid hormones remain attached to thyroglobulin molecule & stored in colloid until secretion
>lg reserve of hormone
99
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
100
Describe thyroid hormones - transport.
-transported in plasma attached to proteins
-thyroxine binding globulin, transthyrein, & albumin
>made by liver
-small amount is free in circulation
>free T4 & T3 diffuse into target cells
>once free T4 has entered most of it will be converted to T3 by iodothyronine deiodinases in cytosol
101
Describe thyroid hormones - deiodinases.
-tissue specific enzymes that can deiodinate thyroid hormones:
>convert T4 to T3 in peripheral tissue
102
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
103
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
104
Describe the different types of actions of thyroid hormones.
1. Increase # & activity of mitochondria
-increase rate of formation of ATP
-cause/consequence of increased activity of cell
2. Increase basal metabolic rate of cells
-BMR = min rate of energy expenditure per unit time at rest
-cell enzymes increase activity in resp to thyroid hormones (ex. Na-K-ATPase)
-weight loss in hyper & weight gain in hypo
3. Stim carbohydrate metabolism
-glu uptake, glycolysis, gluconeogenesis, GI absorption
-secondary to increase in cell metabolic enzymes
4. Fat metabolism
-enhance mobilization & increase FFA
-plasma & liver fat decreased under thyroid stim
>increase LDL receptor in liver & increase CHOL secretion in bile
>hypothyroid = hyperlipidemia & fatty liver
5. Growth & development
-maturation of NS
>reduced mental abilities
-long bones depend on TH to grow & mature
>open epiphyseal growth plates in young hypothyroid
6. Increase blood flow & CO
-vasodilation caused by greater release of end products will increase blood flow = increase in CO
7. Increased HR
-direct effect on excitability of heart
-chronotropic & inotropic effect
8. GI effects
-increase appetite & food intake
-increase GI motility
-diarrhea in hyper
9. Kidney function
-activation of RAAS
-increased blood flow -> increased GFR
10. Neurological effects
-increased wakefulness, alertness & responsiveness to external stimuli
-stim PNS -> increased reflexes, GI tone & motility
105
Describe hypothyroidism.
-decreased syn & secretion of thyroid hormone
-common in dogs, seen in cats following bilateral thyroidectomy as a result of hyperthyroidism
-types:
1. Primary = thyroid gland dysfunction (most common)
2. Secondary = pituitary gland dysfunction (TSH) is rare (pituitary tumor)
3. Tertiary = hypothalamic dysfunction (TRH) is rare
4. Congenital = thyroid gland hyperplasia in foals bc mare diet (low I-)
106
Describe hyperthyroidism.
-most common feline endocrine disorder (rare in dogs)
>thyroid adenoma or benign adenomatous hyperplasia in cats
>thyroid carcinoma in dogs
-overproduction of thyroid hormone
