Week 5

Question 1

What does the adrenal cortex synthesize?

Answer 1

Two classes of hormone corticosteroids (glucocorticoids and mineralocorticoids) & androgens

Question 2

What are mineralocorticoids?

Answer 2

Electrolyte-balance regulating e.g. aldosterone which regulates K+ and Na+ levels in the distal tubules of the kidney, causing them to absorb more sodium and water from the urine… therefore more potassium is secreted in exchange

** stimulates H+ secretion in the collecting duct, regulating plasma bicarbonate and acid/base balance

* can also act on the CNS via the posterior pituitary gland to release ADH- conserves water by direct actions on renal tubular resorption

Question 3

What do glucocorticoids do?

Answer 3

* essential for survival in a fasting animal

* cortisol is a glucocorticoid that affects carbohydrate and protein metabolism

* Protects glucose dependent tissues e.g. brain & heart

* Increases plasma glucose by enhancing mobilizaton of amino acids from proteins in many tissues

* Enhances the ability of the liver to convert these amino acids and glycerol into glucose by activating gluconeogenesis and to store glucose as glycogen

* In the periphery, glucocorticoids diminish glucose utilization and uptake, activate lipolysis, and increase protein breakdown

* Targets most body tissues, including CNS, bone, skin, liver, fat, and muscle

Question 4

What is an example of an androgen precusor and function?

Answer 4

dehydroepiandrosterone (DHEA)- converted to testosterone and estradiol in peripheral tissues

Question 5

What are the three zones of the adrenal cortex and each function?

Answer 5

1. Zona glomerulosa- produces aldosterone
2. Zona fasiculata- produces cortisol and androgens
3. Zona reticularis- produces cortisol and androgens

Question 6

Answer 6

Question 7

Answer 7

Question 8

What regulates glucocorticoid secretion?

Answer 8

Regulated via hypothalamus- pituitary axis- CRH & ACTH

* CRH is released as a consequence of hypoglycaemia, stress, physical trauma, hypoxia, ADH, infection and diurnal secretion (dogs and cats episodic release)

** CRH binds cell surface receptors on corticotrophs and via G proteins and cAMP releases ACTH from the anterior pituitary

** Feedback inhibition– cortisol inhibits pituitary and hypothalamus. ACTH inhibits neuronal cells in the hypothalamus.

Question 9

How are adrenocortical hormones transported and removed?

Answer 9

* Transported in the blood bound to globulin (trancortin) and albumin. 90% of glucocorticoids are bound to protein and have a relatively long half life ~60-90 minutes

* Inactivated by the liver, conjugated with sulphates and glucuronides- decreasing their ability to bind to blood proteins and makes them more water soluble- for excretion in the urine

Question 10

What is the steroid mechanism of action?

Answer 10

* Cortisol and aldosterone bind to glucocorticoid receptor (GR) or mineral corticoid receptors (MR) in the cytoplasm that translocate to the nucleus and modulates transcription in multiple tissues after hormonal binding

Question 11

What are metabolic actions of glucocorticoids?

Answer 11

* Defence against hypocalcaemia: raise blood glucose by increasing liver output of glucose

• decrease utilization of glucose by muscle and adipose tissue
• promotes gluconeogenesis (by inducing synthesis of enzymes)
• promotes proteolysis and inhibits protein synthesis to free up amino acids for gluconeogenesis
• liver synthesis of enzymes involved in the metabolism of amino acids- facilitating conversion to carbohydrates
• In muscle facilitating break down of muscle protein therefore providing amino acid substrate to the circulation and to the liver

* Mobilization of fat from subcutaneous adipose tissue

* Enhance release of glucagon from pancreas alpha cells

* Antagonizes the action of insulin on muscle and adipose tissue

* cortisol must be present for catecholamines to stimulate hormone sensitive lipase

Question 12

Glucocorticoids and inflammation

Answer 12

* inhibit PGs and Leukotriene production (from endothelial cells, macrophages, mast cells, etc.)

* decrease release of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha)

* Reduces IL-2 production therefore inhibiting lymphocyte proliferation

* Reduced proliferation of fibroblast- therefore slow wound healing

Question 13

What is Cushing’s Disease?

Answer 13

Hyperadrenocorticism

* Excess secretion of corticosteroids due to:

• pituitary tumour (85% of cases) over secreting ACTH- normally have two large adrenal glands
• Adrenal tumour
• excess administration of cortico-steroids (iatrogenic) (cortisone = cortisol, predinisone 4 x cortisol, dexamethasone 30 x cortisol)

Question 14

What are the symptom’s of Cushing’s Disease?

Answer 14

* Bulging sagging (pot-bellied) belly

* muscle weakness, loss of muscle mass

* Hair loss and thinning of skin

* weak bones

* bruising

* polyphagia

* PU/PD

* poor wound healing

* Weight gain or redistribution of fat

* susceptibility to infections particularly bladder

* exercise intolerance

Question 15

Why are about 10-20% of dogs with Cushing’s Disease also Diabetic?

Answer 15

* Glucocorticoids decrease utilization of glucose by muscle and adipose tissue and lower sensitivity of these tissues to insulin

Question 16

What is Addison’s disease?

Answer 16

* Insufficiency of adrenocortical hormones

* Rare- autoimmune disease

* Signs: lethargy, weakness, dehydration, collapse

* Low plasma Na+, increased K+, increased BUN (blood urea nitrogen)

Question 17

What does the adrenal medulla secrete? What is the medulla?

Answer 17

* catecholamines: adrenalin and noradrenalin (short half life 10-15 seconds- up to 90% of catecholamines removed from blood on single passage)

* medulla is a modified ganglion- a component of the sympathetic NS

Question 18

What are the major stimuli of the adrenal medulla? How?

Answer 18

* hypoglycaemia, stress, and exercise

* Stimulation of nicotinic ACh receptors opens Ca2+ ion channels on chromaffin cells that produces a localized depolarization and entrance of Ca2+ resulting in exocytosis of adrenaline and noradrenaline

Question 19

Where and from what are adrenalin and noradrenalin synthesized?

Answer 19

Chromaffin cells

* Tyrosine, dopa, dopamine, noradrenalin, adrenalin

Question 20

What are the functions of adrenoceptors?

Answer 20

alpha- 1: increased vascular smooth muscle contraction, mydriasis (constricts radial muscle)

alpha-2: muscle relaxation, sedation, and analgesia (effects on CNS), hypertension, vasoconstriction of arteries to the heart

Beta 1: heart and kidney- increased force cardiac contraction and heart rate, renin release

Beta 2: bronchodilation by relaxation of smooth muscles in bronchi, uterine muscle relaxation, liver- glucose metabolism, smooth muscle relaxation

Beta 3: enhanced lipolysis

Question 21

Metabolic actions of adrenalin

Answer 21

Question 22

Where do large emobli tend to become trapped in the brain? Why are venous occlusions uncommon in the brain?

Answer 22

* Leptomeningeal vessels (where they divide into perpendicular branches)

*at the grey-white matter junction

* venous occlusions are rare because verebral veins are abundant and have many anastamoses

Question 23

What is diploe?

Answer 23

Spongy bone present between two layers of compact bone in the parietal, occipital, and temporal bones of the skull– one of the ways the skull can absorb considerable shock forces (cranial sutures help too and the internal bony ridges of the skull)

Question 24

What are the factors that influence the consequences of skull trauma?

Answer 24

Physical rigidity of bone (age, nutrition, presence of metabolic disease), mass, velocity, and direction of the applied force, the ability of the impacted tissues to move in response to the applied force

Question 25

Why is cerebral trauma often fatal?

Answer 25

Due to the confined space of the cranial cavity. Normally only a narrow space separating the brain from the dura mater. If ICP increases, cerebral structures such as the medulla oblongata and the cerebellar vermis may herniate caudally.

Question 26

Clinical signs of increased ICP

Answer 26

Aniscoria, mydriasis (pupillary dilation), non-responsive pupils, dull mentation, or altered state of consciousness, rigid paresis, abnormal respiration pattern, bradycardia, and coma

Question 27

What is the adenohypophysis? What 3 parts does the adenohypophysis consist of?

Answer 27

Adenohypophysis- anterior lobe of the pituitary 1. pas distalis- bulk of endocrine cells which secrete trophic hormones 2. pas tuberalis- endocrine cells-- mainly acts as a scaffold for the portal blood vessels coursing from the median eminence to the pas distalis 3. pars intermedia- junction between the pas distalis and the pars nervosa and contains endocrine cells (separated by a cleft- not in horse- the residual lumen of Rathke's pouch)

Question 28

What is the neurohypophysis?

Answer 28

\* Posterior lobe of the pituitary

Question 29

What are acidophils?

Answer 29

\* secretory endocrine cells of the adenohypophysis-- secretory granules stain red with H& E \* somatotrophs= cells secreting growth hormone (somatotropin) \* luteotrophs= cells secreting luteotropic hormone (LTH) (prolactin)

Question 30

What are basophils in the adenohypophysis?

Answer 30

Secretory granules stain blue with H& E stain \* gonadotrophs= cells secreting luteinising hormone (LH) and follicle stimulating hormone (FSH) \* thyrotrophs= cells secreting thyroid stimulating hormone (TSH)

Question 31

What are chromophobes?

Answer 31

\* secretory endocrine cells of the adenohypophysis-- not discernible with H& E stain \* Corticotrophs= cell secreting adrenocorticotropic hormone (ACTH) \* melanotrophs= cells secreting melanocyte stimulating hormone (MSH) \* degranulated acidophils and basophils \* undifferentiated stem cells \* non-secretory cells

Question 32

What are the endocrine cells of the adenohyphophysis under control of?

Answer 32

Corresponding releasing hormone derived fro neurons of the hypothalamus by neurosecretion \* the releasing hormones are transported along the axonal processes of the secretory neurons to the median eminence--\> release into capillaries--\> transport by blood vessels of the pituitary protal system--\> target endocrine cells in the adenohypophysis which rapidly release their secretory granules into the blood

Question 33

What is the control of most pituitary trophic hormones?

Answer 33

Negative feedback control achieved by the blood concentration of the hormone produced by the target endocrine glands e.g. thyroxine from the thyroid glands, cortisol from the adrenal cortices, oestrogen or progesterone from the ovaries, androgens from the testes, etc. \*\* negative feedback is exerted either on the hypothalamic neurosecretory neurons or on the adenohypophyseal trophic hormone secreting cells or both

Question 34

How do GH, prolactin (LTH), and MSH stimulate secretion of a hormone?

Answer 34

NOT by acting on target endocrine organs but by means of releasing inhibitory hormones produced by hypothalamic neurons. \* dopamine is the main releasing factor for prolactin (LTH) \* somatostatin is the main release inhibiting factor for GH (somatostatin is also produced by pancreatic islet cells)

Question 35

What are supraoptic nuclei?

Answer 35

Neurons of these nuclei in the hypothalamus synthesise antidiuretic hormone (ADH; vasopressin)

Question 36

What are paraventricular nuclei?

Answer 36

Neurons of these nuclei in the hypothalamus synthesise oxytocin

Question 37

How is ADH secreted into general circulation?

Answer 37

\* ADH and its corresponding binding protein (neurophysin I) are packaged into neurosecretory granules and transported to the pars nervosa of the pituitary gland by axonal processes of the hypothalamic neurosecretory neurons; the axons terminate on fenestrated capillaries in the pars nervosa, permitting release of ADH directly into general circulation

Question 38

What is the function of ADH?

Answer 38

Acts on distal tubules and collecting ducts of the kidneys to cause water resorption from the glomerular filtrate and hence increased urine concentration

Question 39

What is the function of oxytocin?

Answer 39

Contraction of smooth muscle fibres in the uterus and myoepithelial cells in mammary tissue

Question 40

What are the three parts of the neurohypophysis?

Answer 40

1. median eminence: site where axons of the hypothalamic neurosecretory neurons release hypothalamic releasing hormones/ factors into capillaries to influence the endocrine cells of the adenohypophysis 2. infundibular stalk= pituitary stalk: composed on non-myelinated axonal processes from the hypothalamic neurosecretory neurons of the supraoptic and paraventricular nuclei... joins the pars nervosa to the overlying hypothalamus 3. pars nervosa- contains numerous capillaries which are termination sites for the axonal processes of the hypothalamic neurosecretory neurons producing oxytocin and ADH

Question 41

Answer 41

pituitary gland (arrow)

Question 42

Answer 42

Question 43

Answer 43

Question 44

Answer 44

Question 45

Answer 45

Later term human foetal brains in which there has been failure of successful differenation of the prosencephalon into derivative structures (holoprosencephaly= prosencephalic hypoplasia)

Question 46

Answer 46

Cyclopia- most severe expression of holoprosencephalon (excessive wool growth reflects prolonged gestation due to partial or complete failure of development of the hypothalamus and/or posterior pituitary. Therefore a delay in or complete absence of the foetal cortisol surge which triggers the parturition process.

Question 47

Answer 47

Veratrum californicum (lamb's bane, skunk cabbage)- steroidal alkaloids induce holoprosencephaly in foetal lambs if their dams consume the plant between days 9 and 14 of pregnancy

Question 48

Answer 48

Question 49

Answer 49

Foetal calf with cessation of growth and development at approximately 7 months of gestation due to hypoplasia of the adenohypophysis and hence inadequate pituitary tropic hormone production

Question 50

Answer 50

Cauliflower saltwort in Africa- last 50 days of pregnancy may have parturition delayed by 10-20 days, possibly by inhibition of release of foetal hypothalamic releasing hormones

Question 51

Development of the pituitary gland

Answer 51

\* down growth of neuroectodermal tissue from diencephalon - gives rise to posterior pituitary... has to grow ventrally and make contact with organ up growth (ectodermal tissue from the oropharynx)-- ultimately when it joins up and matures--\> gives rise to anterior pituitary---\> eventually separated from oropharyngeal ectoderm because bone forms (sphenoid bone). \* Rathke's pouch refers to the up growth

Question 52

Arrow? What can happen if this stays open?

Answer 52

A residual cleft (arrows) that is the remnant of the embryonic Rathke's pouch detectable microscopically. If Rathke's pouch stays open--\> PITUITARY CYST

Question 53

Answer 53

Pituitary cyst

Question 54

Answer 54

Pituitary cyst-- gradually enlarges

Question 55

Litter mates. What's the problem? What are the causes?

Answer 55

Pituitary Dwarfism- over represented in German Shepherds. Autosomal recessive. Inadequate growth hormone. Usually becomes apparent from approximately 2 months of age. \*\* pituitary cyst, craniopharyngioma (ectodermal remnants of Rathke's pouch)

Question 56

Answer 56

Pituitary abscess in a calf -- purulent exudate tracking along the ventral floor of the cranial vault to the foramen magnum \*\* grass awns tracking along the optic nerve from the orbit or circle of willis or bacteria can ascend from superficial skin infections along the deep valveless veins of the face into the cranial vault

Question 57

Non-functional tumours of the pituitary

Answer 57

Space occupying- compression of surrounding structures. Visual deficits, central blindness, pupillary dilation issues, trigeminal nerves

Question 58

What are some of the signs and symptoms of hypothalamic pituitary disorders?

Answer 58

\* example: infertility due to not enough FSH/ LH produced \* obesity: polyphagic- pressing on appetite and satiety centers \* space occupying mass in a tight space = neurological signs due to ICP \* OR pituitary cachexia can also occur due to lack of growth hormone

Question 59

Answer 59

pituitary macroadenoma in a dog

Question 60

Answer 60

Functional pituitary tumours- Pars distalis (sometimes pars intermedia) \* in the pars distalis can get really big-- easily compress CNs \* Producing too much ACTH will cause bilaterally enlarged adrenal cortices-- overproducing cortisol-- therefore hyperadrenocorticoid

Question 61

Answer 61

Cushing's Disease (tumour) vs. Cushing's Syndrome (iatrogenic due to corticosteroids)

Question 62

Answer 62

Pituitary Pars Intermedia Dysfunction (PPID) \*\* EXCESS pro-OLMC precursor produced by chromaphobe cells of the tumours in horses-- serum cortisol and ACTH concentrations are only mildly increased or NORMAL-- \* polyphagia, PU/PD, weight gain (pot-bellied), docility/ sleepiness, failure of seasonal shedding of the hair coat, excessive sweating, chronic recurrent laminitis \* due to compression of the hypothalamus by a tumour

Question 63

Clinical presentation of PPID

Answer 63

Question 64

Answer 64

\* less peripheral effects, but issues with sphenoid bone (lysis) and compression of overlying structures

Question 65

Acromegaly due to development of the functional acidophil tumour of the pituitary

Answer 65

\* visual effects, polyphagia, PU/PD, eventually become diabetic because they are eating more--\> pancreas produces more insulin--\> insulin resistant diabetes

Question 66

Where do the adrenal cortex and medulla derive from? What is the ratio?

Answer 66

Question 67

What parts of the adrenal gland secrete what?

Answer 67

Salt, sugar, sex--\> the deeper you go, the sweeter it gets

Question 68

With cortisol and aldosterone, which has to do with the pituitary?

Answer 68

Cortisol

Question 69

What happens with adrenal agenesis?

Answer 69

\* Bilateral= lethal... no mineralcorticoids so severe electrolyte and fluid imbalances... Unilateral= clinically normal

Question 70

Answer 70

Amyloid deposition or adrenal mineralization

Question 71

Why is adrenal haemorrhage common?

Answer 71

Thin walled- so susceptible to haemorrhage especially horses who have died on the race track. \* neonates who have been "squeezed out" \* DIC \* septicaemia (if they survive, they can end up with adrenal insufficiency- rare)

Question 72

Answer 72

Adrenal haemorrhage

Question 73

Answer 73

Adrenalitis- common, sequestered from the immune system to some extent \*\* autoimmune disease as well- common in dogs

Question 74

What are the two most common drugs causing adrenal toxicity?

Answer 74

Question 75

Answer 75

Question 76

Answer 76

Question 77

Nodular hyperplasia vs. adenoma

Answer 77

Hyperplasia is a normal response, whereas adenomas have abnormal stimulus

Question 78

Answer 78

Question 79

Answer 79

Question 80

Cushing's Disease- what are the four forms?

Answer 80

\* hyperadrenocorticism- excess cortisol \* (Atypical hyperadrenocoricism (show clinical features, but do not actually secrete excess cortisol)- possibly due to androgens and oestrogens) 1. Pituitary dependent: Functional tumour in the anterior pituitary- continually produces ACTH because there is no feedback to the anterior pituitary, unresponsive to cortisol feedback 2. Adrenal Dependent: adrenal neoplasm secretes excess cortisol independent of ACTH 3. Iatrogenic: corticosteroids 4. Ectopic ACTH secretion- paraneoplastic syndrome producing ACTH- often a tumor e.g. lung tumour

Question 81

What is Conn's Disease?

Answer 81

Hyperaldosteronism

Question 82

Answer 82

Question 83

Answer 83

Question 84

Answer 84

Question 85

Answer 85

Question 86

Answer 86

Question 87

Signs and symptoms of Hyperadrenocorticism

Answer 87

Question 88

Answer 88

Calcinosus cutis

Question 89

Where are the two feedback mechanism with the HPAA axis?

Answer 89

\* Cortisol on the Hypothalamus and pituitary

Question 90

Hyperadrenocorticism in cats signs and symptoms

Answer 90

Question 91

Hyperadrenocorticism in horses or pituitary pars intermedia dysfunction (PPID)?

Answer 91

Question 92

What are haematology findings with Hyperadrenocorticism (HyperA)?

Answer 92

Persistent stress leukogram

Question 93

Why lymphopenia in a stress leukogram?

Answer 93

Sequestration of lymphocytes in nodes, spleen, and bone marrow \* lysis of thymic cortical lymphocytes and uncommitted lymphotes

Question 94

Why a mature neutrophilia in a stress leukogram? Monocytosis? Eosinopenia?

Answer 94

Increased marrow release from storage pool, decreased emigration from tissues. Shift from marginating--\> to circulating pool \*\* monocytosis also from marginating pool to circulating pool \*\*inhibition of marrow release and inhibition of IL-5 production

Question 95

Biochem findings with HyperA

Answer 95

\* Elevated Liver enzymes - elevated ALP (cholestasis- hepatocyte swelling (glycogen)) - elevated GGT (cholestasis) - elevated ALT +/- AST: hepatocyte damage \* Hypercholestraemia (increase in hormone sensitive lipase mobilizing fat in some parts of the body) \* Lipaemia- hypertriglyceridaemia \*Hyperglycaemiainsulin- antagonism (increased gluconeogenesis increased glucagon release; decreased GLUT-4 transporters) \* Low TT4 \* Mild elevation in urea (pre renal azotaemia)

Question 96

Routine urinalysis findings with HyperA

Answer 96

(UTI prone due to suppressed immune system)

Question 97

Testing Options for HyperA

Answer 97

\*\* keeping in mind stressed animals at the vets may have abnormal levels -- overdiagnosed

Question 98

Urinary cortisol- creatinine ratio (UCCR)

Answer 98

\* highly sensitive test- will detect almost all cases \* poor specificity (23%)- UCCR elevated with stress or illness \* test two free catch morning samples collected at home (to minimize stress) \*rule out test, not a confirmatory test \*\*\* \* Normal dogs UCCR \< 17.5

Question 99

Low dose dexamethasone suppression test (LDDST)

Answer 99

Measure levels before and after giving exogenous corticosteroids... if they have pituitary dependent hyperA or adrenal dependent hyperA... normal dog SHOULD SUPPRESS PRODUCTION for about 8 hours... Why do we do a 3 and 8 hours?? To differentiate between pituitary dependent PDH and adrenal dependent.... \* high sensitivity (95%)-- most dogs will be detected with this test!! Problem is: normal stress (drive to produce cortisol is overriding the feedback mechanism\*\*\*\*) \* Moderate specificity (44-73%) \* adrenal tumours show lack of suppression \* pituitary dependant hyperA (PDH) can show partial suppression (75%) or no suppression (25%) \* Partial or no suppression with stress

Question 100

What is the unique thing about horses interpreting overnight DST?

Answer 100

Question 101

ACTH stim test

Answer 101

Stimulates adrenal glands to make more cortisol. Depending on the size of the adrenal gland, it will depend on how the animal will respond. Great big= respond more than an animal with smaller. \*\* more false negatives-- lower sensitivity than LDDST BUT not as many false positives \*\* does not differentiate PDH from ADH

Question 102

How does the ACTH stim test work?

Answer 102

Give ACTH-- pump out cortisol from large adrenal glands. With ADH-- give ACTH-- stimulates greater production of cortisol from the mass AND from the normal tissue. FEEDBACK DOES NOT WORK in either PDH or ADH

Question 103

With iatrogenic hyperA, what happens?

Answer 103

Atrophy of adrenal glands.

Question 104

WHat is meant by equivocal in the ACTH stim test?

Answer 104

\* not high enough to diagnose hyperA

Question 105

Which test is best for hyperA?

Answer 105

Large dog- LDDST (unless overly nervous) Small dog- ACTH stim test (if nervous) \* also depend on owner finances, how long clinic is open for e.g. the second, 8 hour sample, LDDST might be better if no access to ultrasound to help localize

Question 106

High Dose Dexamethasone Suppression test

Answer 106

Uncommon these days \* sampling at 4 and 8 hours \* with Adrenal tumours fail to suppress \* PDH show suppression in most cases (70%)

Question 107

Endogenous ACTH

Answer 107

\* can measure-- PDH problem... ACTH will be high... if adrenal tumour-- then low ACTH \*PPID have high levels- beware of seasonal variation \* Labile, special collection and handling procedures

Question 108

Adrenal imaging as a localizing test

Answer 108

\* dogs with PDH will have bilateral adrenal enlargement \* dogs with adrenal tumours will have one large adrenal and one small adrenal gland (atrophied) \* imaging of pituitary gland to identify mass

Question 109

Hypoadrenocorticism major DDX

Answer 109

"the great pretender" \* renal insufficiency \* urinary obstruction \* GIT disease \* hypercalcaemia of malignancy

Question 110

Clinical signs and symptoms of Addison's disease?

Answer 110

Vague signs. \* Weakness and lethargy \* vomiting, diarrhoea, abdominal pain \* collapse \* bradycardia (hyperkalaemia) \* PU/PD \*dehyrdation \* tremors/shaking \* GIT haemorrhage \* often waxing and waning signs

Question 111

Causes of Hypoadrenocorticism

Answer 111

\* Primary adrenal gland failure \*failure of ACTH secretion \* iatrogenic (sudden withdrawal from corticosteroids) \* critical illness--\> relative adrenal insufficiency (transient/ reversible) (adrenal crisis)

Question 112

Haematological findings with Addison's disease in dogs

Answer 112

\* lack of stress lymphopenia but they are sick!! (may be the only sign you have)

Question 113

Biochem findings with Addison's Disease

Answer 113

Question 114

How do you test for Addison's Disease?

Answer 114

\*\* may run a basal cortisol level\*\* (exclusion test, not confirmatory)

Question 115

What hormone is produced by the parathyroid? What is its function?

Answer 115

parathyroid hormone by the chief cell Regulates serum calcium and phosphorous levels. Acts to increase serum Ca levels by enhancing absorption from the GIT and mobilization from bone as well as limiting excretion in the urine. Serum phosphorous levels are also affected in that they decline due to increased excretion in the urine. The parathyroid cells are sensitive to serum Ca levels, decreasing serum Ca levels stimulates the release of parathormone.

Question 116

What is the eosinophilic material contained within the follicles of the thyroid?

Answer 116

Colloid- which is the storage form of thyroid hormone. Colloid is a glycoprotein called thyroglobulin, the storage or intermediary form of thyroid hormone

Question 117

What hormones are produced by the follicular cells? Parafollicular cells?

Answer 117

Follicles: thyroxine (thyroid hormone or T4) Parafollicular cells: calcitonin (thyrocalcitonin) \*\* thyroglobulin (storage form of thyroxin (T4))- is iodonated in the lumen-- and synthesizes thyroxine (T4) and triiodothyronine (T3)-- which are then released into circulation. Influence metabolic rate!!

Question 118

Answer 118

Question 119

What are the hormones that are released from the pars nervosa?

Answer 119

Oxytocin and ADH (peptide hormones). \*\* synthesized in the cell bodies of the supraoptic nucleus (ADH) and paraventricular nuclei (oxytocin) of the hypothalamus

Question 120

How does MSH travel from the pars nervosa into the blood stream?

Question 121

What hormone is synthesized by the pars intermedia?

Answer 121

In the neurohypophysis (posterior pituitary) The main cell type- melanotrope is a large pale staining cell with submicroscopic granules (MSH)-- function is to produce intermedin (MSH or melanocyte stimulating hormone) which acts to increase pigmentation and may play a role in controlling body cyclic rhythms e.g. reproductive cycles

Question 122

What hormones does the medulla produce?

Answer 122

epinephrine and norepinephrine-- stimulated by the sympathetic NS under stressful conditions.

Question 123

What is the chemical nature of the hormones of the cortex?

Answer 123

Aldosterone (zona glomerulosa) & glucocorticoid hormones e.g. cortisol (zona fasciculata).... steroid hormones- cholesterol & lipids

Question 124

What cell organelle and cytoplasmic inclusion characterize cells producing hormones of this chemical nature?

Answer 124

Smooth endoplasmic reticulum (sER), mitochondria, Golgi apparatus and lipid droplets.

Question 125

What is the peak time of concentration in blood of thiopentone?

Answer 125

2 seconds (brain is the same)

Question 126

As blood and brain concentration fall, where has the drug gone?

Answer 126

Muscle and fat

Question 127

Effect of a reduction in fat comparment on speed of decline of blood and brain concentrations?

Answer 127

Slower decline with a single bolus.

Question 128

What evidence is there for hepatic clearance of thiopentone ??

Answer 128

None it is just traveling through the liver-- no break down whatsoever.

Question 129

Which drug concentration falls the fastest with thiopentone after you stop adding boluses? Why is this so?

Answer 129

Muscle.

Question 130

What happens with thiopentone with multiple boluses?

Answer 130

Stored in fat. Roller coaster curve but slightly increasing over time.

Question 131

What consequences can you predict from this data for administration of multiple "top up" doses during anaesthesia using thipentone?

Answer 131

Using smaller doses due to the additive effect as well as if you want it to clear faster. Fat vs. thin. Fat dog bigger hang over. Thin dog stays asleep longer. Not as safe as alfaxan.

Question 132

What is the time of the peak concentration in blood of alfaxalone?

Answer 132

2 seconds, brain peaks closest to it

Question 133

What is the half life of elimination of alfaxan in time units?

Answer 133

5.9 seconds

Question 134

As blood and brain concentration falls-- where has the drug gone? Reduction in fat compartment effect??

Answer 134

Drug is simply excreted after metabolized by the liver. No effect on speed of decline with a reduction in fat compartment.

Question 135

What evidence is there for hepatic clearance of alfaxan?

Answer 135

Liver is clearing- as in the hepatic vein there is less than half as compared to the hepatic artery.

Question 136

When giving IV alfaxan, what consequences can you predict from top up doses? When giving as an infusion, what is the time to steady state concentration? What does this mean for protocol for induction and maintenance of anaesthesia with alfaxan?

Answer 136

\* you give it the opportunity to clear with top up doses-- but perhaps it would not keep the patient anaesthetized \* infusion- 28.7 seconds to steady state vs. 1.7 seconds-- so we are giving a smaller concentration with infusion (perhaps additive?) \*\* you would give an induction agent, so you wouldn't have 30 seconds to go under... or come out if you don't give the right (dose?) for infusion

Question 137

In a patient with liver impairment, what would the new half life of alfaxan?

Answer 137

8.7 vs. 5.9 seconds in a normal patient with normal liver function

Question 138

What would you see with an LDDST with PDT? Why?

Answer 138

Partial or no suppression at 4 hours- then kicking up again at 8 hours \*\*Dexamethasone is a corticosteroid not detected by the cortisol assay that causes suppression of CRH and ACTH release, leading to a marked decrease in cortisol release from adrenal glands. In normal dogs, this suppression lasts 8 hours-- but in a pituitary dependent hyperA dog-- the excess secretion of ACTH causes marked adrenal gland enlargement (cortical hyperplasia) and hence greater release of cortisol... and with the LDDST we will see either no suppression (total loss of normal negative feedback of pituitary adenoma continues to release ACTH, so cortisol levels do not significantly fall)-- same response as in adrenal tumours (25% of PDH cases), OR early escape from suppression-- lowers it but cortisol levels rebounded by 8 hours, OR partial suppression of CRH and ACTH release- leading to a mild decrease in cortisol release from the adrenal glands... they do not fall below 30 nmol/L

Question 139

What will you see with LDDST with ADH? Why?

Answer 139

Failure to suppress. Due to a functional tumour of the adrenal glands pumping out cortisol without the requirement for ACTH release. Typically ACTH levels in these dogs are extremely low.... so the negative feedback mechanism has no effect.

Question 141

What would you see in the ACTH stim test with hyperadrenocorticism? Why?

Answer 141

\*\* Normal dogs stimulated with ACTH-- \< 470 nmol/L after one hour \*\* HyperA dogs \>550 nmol/L \*\* Equivocal (a little high but not high enough to know for sure) 470-550 nmol/L You are not trying to differentiate. Better used on small dogs. Big dogs are more likely to have ADH if they have hyperA. More false negatives, but less false positives.

Question 142

When is high dose dexamethasone suppression test used? What would you see with PDH? ADH?

Answer 142

Localizing the lesion BUT not often used anymore \* PDH- most dogs show suppression (70%) \* ADH- most dogs show no suppression (difference between this and low dose- teases out some of the animals on the fence)

Question 143

Other than imagining and high dose dex test, what is the other option for localizing hyperA? What about horses? Iatrogenic cases?

Answer 143

\* Endogenous ACTH \* dogs with PDH have normal to high levels of enogenous ACTH \* dogs with ADH have very low levels \* Horses with PPID-- have high levels of ACTH (but beware of seasonal variation) \* Iatrogenic hyperA cases have very low levels

Question 144

How do you test for Addison's Disease?

Answer 144

Primary adrenal gland failure or Iatrogenic (sudden withdrawal) \*\* Haematology- lack of stress leukogram in a sick dog \*\* Biochemistry- low sodium, high potassium, low glucose, high calcium, azotaemia