Endocrinology Flashcards

Question

Neurohypophysis -> supraoptic nucleus (SON)

Answer 1

Secretes antidiuretic hormone (ADH, aka vasopressin) After it’s created it is transported down the axons, in synaptic vesicles by specific motor proteins. The vesicles need certain stimuli to release the ADH o ↓ blood volume → ↓ blood pressure o ↑ plasma osmolality o Pain Inhibitors of the ADH secretion o ↑ blood volume o ↓ plasma osmolality o Alcohol REMINDER: Osmolality refers to the concentration solutes and water inside the plasma o High plasma osmolality - ↓ water, ↑ solutes -> hypertonic plasma o Low plasma osmolality - ↑ water, ↓solutes -> hypotonic plasma o Osmoreceptors - register the plasma osmolality -> high osmolality stimulates the receptors

Answer 2

1) Increases H20 permeability (aquaporin 2, AQP2) of the principal cells of the late distal tubule and collecting duct (via a V2 receptor and an adenylate cyclase-cAMP mechanism). 2) Constriction of vascular smooth muscle (via a V1 receptor and an IP3 /Ca2+ mechanism). 3) Increased Na+-2CI--K+ cotransport in thick ascending limb, leading to increased countercurrent multiplication and osmotic gradient. 4) Increase urea recycling in inner medullary collecting ducts, leading to increased osmotic gradient.

Answer 3

In the paraventricular nucleus in the hypothalamus

Answer 4

1) Suckling is the major stimulus for oxytocin secretion. Afferent fibers carry impulses from the nipple to the spinal cord. Relays in the hypothalamus trigger the release of oxytocin from the posterior pituitary. The sight or sound of the infant may stimulate the hypothalamic neurons to secrete oxytocin, even in the absence of suckling. 2) Dilation of the cervix and orgasm increases the secretion of oxytocin.

Answer 5

1) Contraction of myoepithelial cells in the breast Milk is forced from the mammary alveoli into the ducts and ejected. 2) Contraction of the uterus - during pregnancy, oxytocin receptors in the uterus are up-regulated as parturition approaches, although the role of oxytocin in normal labor is uncertain. Oxytocin can be used to induce labor and reduce postpartum bleeding

Answer 6

The hypothalamic releasing and inhibitory hormones.

Answer 7

- Usually, there is one cell type for each major hormone formed in the anterior pituitary gland. - Somatotropes - growth hormone (GH) - 30-40% of the cells - Corticotropes - adrenocorticotropic hormone (ACTH) - about 20% of the cells - Thyrotropes - thyroid stimulating hormone (TSH) - 3-5% of the cells - Gonadotropes - gonadotropic hormones - Luteinizing hormone (LH and follicle stimulating hormone (FSH) - 3-5% of the cells - Lactotropes - prolactin (PRL) - 3-5% of the cells.

Answer 8

Peptides, polypeptides or derivatives of tyrosine.

Answer 9

- Growth hormone is released in pulsatile fashion. - Secretion is increased by sleep, stress, hormones related to puberty, starvation, exercise, and hypoglycemia. - Secretion is decreased by somatostatin (aka growth hormone inhibitory hormone), somatomedins, obesity, hyperglycemia, and pregnancy. 1) Hypothalamic control -> GHRH and somatostatin - GHRH stimulates the synthesis and secretion of growth hormone. - Somatostatin inhibits secretion of growth hormone by blocking the response of the anterior pituitary to GHRH. 2) Negative feedback control by somatomedins - Somatomedins are produced when growth hormone acts on target tissues. Somatomedins inhibit the secretion of growth hormone by acting directly on the anterior pituitary and by stimulating the secretion of somatostatin from the hypothalamus. 3) Negative feedback control by GHRH and growth hormone - GHRH inhibits its own secretion from the hypothalamus. - Growth hormone also inhibits its own secretion by stimulating the secretion of somatostatin from the hypothalamus.

Answer 10

- In the liver, growth hormone generates the production of somatomedins (IGFs),which serve as the intermediaries of several physiologic actions. - The IGF receptor has tyrosine kinase activity, similar to the insulin receptor 1) Direct actions of growth hormone - Decreases glucose uptake into cells (diabetogenic). - Increases lipolysis. - Increases protein synthesis in muscle and increases lean body mass. - Increases production of IGF. 2) Actions of growth hormone via IGF - Increases protein synthesis in chondrocytes and increases linear growth (pubertal growth spurt). - Increases protein synthesis in muscle and increases lean body mass. - Increases protein synthesis in most organs and increases organ size.

Answer 11

Somatostatin (aka growth hormone inhibitory hormone)

Answer 12

In children causes dwarfism, failure to grow, short stature, mild obesity, and delayed puberty. Can be caused by: (a) Hypothalamic dysfunction (decreases in GHRH). (b) Lack of anterior pituitary growth hormone. (c) Failure to generate IGF in the liver. (d) Growth hormone receptor deficiency.

Answer 13

Hypersecretion of growth hormone causes acromegaly. (a) Before puberty, excess growth hormone causes increased linear growth (gigantism). (b) After puberty, excess growth hormone causes increased periosteal bone growth, increased organ size, and glucose intolerance Can be treated with somatostatin analogues (e.g., octreotide), which inhibit growth hormone secretion.

Answer 14

- Is the major hormone responsible for lactogenesis. - Participates, with estrogen, in breast development. - Is structurally homologous to growth hormone.

Answer 15

1) Hypothalamic control by dopamine and thyrotropin-releasing hormone (TRH) - Prolactin secretion is inhibited by dopamine (prolactin-inhibiting factor [PIF]) secreted by the hypothalamus. Thus, interruption of the hypothalamic-pituitary tract causes increased secretion of prolactin and sustained lactation. - TRH increases prolactin secretion. 2) Negative feedback control -> prolactin inhibits its own secretion by stimulating the hypothalamic release of dopamine.

Answer 16

1) Stimulates milk production in the breast. 2) Stimulates breast development (in a supportive role with estrogen). 3) Inhibits ovulation by decreasing synthesis and release of gonadotropin-releasing hormone (GnRH). 4) Inhibits spermatogenesis (by decreasing GnRH).

Answer 17

1) Prolactin deficiency (destruction of the anterior pituitary) -> results in the failure to lactate. 2) Prolactin excess - Results from hypothalamic destruction (due to loss of the tonic "inhibitory" control by dopamine) or from prolactin-secreting tumors (prolactinomas). - Causes galactorrhea and decreased libido. - Causes failure to ovulate and amenorrhea (absence of menstruation) because it inhibits GnRH secretion. - Can be treated with bromocriptine, which reduces prolactin secretion by acting as a dopamine agonist.

Answer 18

- Located in the anterior neck - just below the larynx of the voice box - Butterfly shaped - Consists of thyroid follicles -> structural and functional unit of the thyroid gland. They are made up of simple cuboidal epithelial cells called follicular cells.

Answer 19

Thyroxine - T4 (about 93%) Triiodothyronine - T3 (about 7%)

Answer 20

1) The synthesis begins in the paraventricular nuclei (PVN) inside the hypothalamus, secreting thyrotropin-releasing hormone (TRH). 2) TRH goes in the hypophyseal portal system to the anterior pituitary and stimulates specific cells -> the thyrotropes, to secrete thyroid stimulating hormone (TSH) into the bloodstream. 3) TSH (it is a peptide hormone) goes to the follicles of the thyroid gland and binds to receptors present on the cell membrane -> it activates a G stimulatory protein (2nd messenger is adenylate cyclase) -> will convert ATP into cAMP and activate protein kinase A (pkA). 4) Activated pkA goes into the cell nucleus and stimulates genes to start producing thyroglobulin colloid

Answer 21

- To produce thyroid hormone - it is ingested with different nutrients (iodized salt). - It circulates in the bloodstream in ion form (called iodide, has a negative charge)

Answer 22

- It has be to be transported from area with low concentration (blood) to area with high concentration (follicular cells) - Sodium uses passive transport to go from an area with high concentration (blood) to area with low concentration (follicular cells) -> iodide cotransports with it (secondary active transport - an indirect use of ATP). - A specific protein called pendrin transports iodide from the follicular cells into the luminal space.

Answer 23

There is an enzyme called thyroid peroxidase that has three functions: 1) Iodine oxidation o Converts iodide into iodine -> iodide loses an electron (loses its negative charge, oxydation) -> becomes neutral 2) Iodination o Attaches 1 or 2 iodine molecules to the tyrosine amino acids in the thyroglobulin colloid - 1 molecule creates monoiodotyrosine (MIT) - 2 molecules create diiodotyrosine (DIT) 3) Coupling o Couples the iodinated tyrosine amino acids into thyroxine (T4) and triiodothyronine (T3) - Diiodotyrosine and diiodotyrosine (DIT+DIT) creates T4 - Diiodotyrosine and monoiodotyrosine (DIT+MIT) creates T3 o Apart from thyroid peroxidase there are other enzymes that help the coupling reaction with cleavage processes and rearrangements T3 and T4 collectively are the thyroid hormone (TH)

Answer 24

1) The iodinated thyroglobulin goes inside the follicular cells via endocytosis o Ends up inside vesicles - then the vesicles fuse with lysosomes o The lysosomal enzymes cut the thyroglobulin to isolate the T3 and T4 Then the vesicles containing the T3 and T4 fuse with the cell membrane to release the thyroid hormones into the bloodstream. 2) The tyrosine amino acid contains a benzene ring inside its molecule, therefore, T3 and T4 are not water soluble o In the blood T3 and T4 bind to a transporting protein -> thyroxine binding globulin (TBG, synthesized by the liver).

Answer 25

- T4 is converted to T3 by 5'-iodinase (or to rT3). - T3 is more biologically active than T4. - rT3 is inactive.

Answer 26

- Cells - Liver - Heart - CNS - Bones - Adipose tissue - Muscle - Integumentary system - GI

Answer 27

1) Thyroid hormone (T3 and T4) circulates the bloodstream bound to thyroxine binding globulin (T4 is major component) -> passes through the lipid bilayer of the cellular membrane. 2) Inside the cell the enzyme 5’-deiodinase removes an iodine form thyroxine, converting T4 into T3 (the active form of the thyroid hormone). 3) T3 binds to a transcription factor -> to exert its effects, it needs retinoic acid (RXR) to bind to the transcription factor as well. When both substances bind to the transcription factor o It is activated o Moves inside the nucleus o Stimulates a specific gene sequence 4) The gene sequence undergoes transcription, translation and modifications o The end result is the synthesis of a protein -> sodium-potassium ATPase -> merges with the cell membrane pumps 3Na+ out - 2K+ inside, ATP dependent process -> will deplete ATP. 5) This ATP depletion will force the cells to start "burning more fuel" to increase the ATP -> more consumption of carbohydrates, lipids and proteins to produce ATP. - Increased O2 consumption - Increase metabolic rate - Increase heat production - Increase number of mitochondria - Hyperthrophy of the mitochondria

Answer 28

Produces proteins that stimulate - Glycogenolysis (conversion of glycogen into glucose) -> BG goes into the blood, increasing its levels. - Gluconeogenesis -> conversion of non-carbohydrates into glucose (glycerol, amino acids and lactate located in the liver). - The expression of LDL receptors (LDL-R) -> increases numbers of LDL receptors, increases LDL uptake and decreases LDL levels in blood (LDL - low-density lipoproteins - bad cholesterol).

Answer 29

1) On the cardiomyocytes -> stimulates the expression of B1-adrenergic receptors -> they bind epinephrine and norepinephrine: increases contractility, stroke volume -> cardiac output -> increases in BP. 2) TH also affects the non-contractile muscle cells of the SA node and the AV node Stimulates the expression of B1-adrenergic receptors -> they bind epinephrine and norepinephrine: increases action potentials -> increases heart rate -> increases BP.

Answer 30

↑ dendrite formation -> increase number of neural connections ↑ myelination -> faster action potentials ↑ number of synapses -> increases number of chemical reactions between neurons. As a result of all this hyperthyroidism can lead to anxiety and irritability

Answer 31

1) In the bones there are two types of important cells o Osteoblasts -> responsible for bone deposition o Osteoclasts -> responsible for bone resorption 2) TH regulates and maintains the balance between the two o Prevents excessive osteoblastic or osteoclastic activity o The process is called bone remodeling 3) TH affects the chondrocytes in the epiphyseal plates o The chondrocytes undergo proliferation, hypertrophy and eventually ossification o This causes the bones to grow in length -> interstitial growth 4) TH stimulates endochondral ossification (turning cartilage into bone).

Answer 32

TH stimulates lipolysis: - The process of of breakdown of triglycerides (main component of the adipose tissue) into fatty acids and glycerol by activating specific enzymes - The produced glycerol goes to the liver and is converted into glucose via gluconeogenesis

Answer 33

1) The protein metabolism is the sum total of catabolism (conversion of proteins to amino acids) and anabolism (conversion of amino acids into proteins). 2) TH regulates the activity of both keeping them balanced 3) Hyperthyroidism causes the balance shifts to catabolism -> weak, atrophied muscles, weak muscle movements (not to be mistaken with lethargy).

Answer 34

1) Skin - Epidermis - Dermis - contains the blood vessels that provide nutrition 2) TH increases the metabolic rate -> increases internal body temperature. - The body tries to regulate it. Blood vessels dilate and increase the blood flow -> the skin to look soft and flushed and radiates heat. - The apocrine and merocrine sweat glands start producing sweat -> TH ↑ the sweat glands sensitivity to catecholamines (epi and norepinephrine) -> increases sweat production -> when sweat is on the skin -> evaporative cooling. 3) Hypothyroidism causes brittle nails and thin hair 4) Hyperthyroidism causes thick hair

Answer 35

1) TH stimulates the secretions of the entire GI tract o Alkaline fluid o Intestinal fluid, etc. 2) TH enhances the motility of the entire GI tract -> stimulates the contractions of the smooth muscle cells. Hyperthyroidism causes diarrhea Hypothyroidism causes constipation

Answer 36

The parathyroid glands are located in the posterior aspect of the thyroid gland There are generally 4 parathyroid glands Parathyroid glands consist of two types of cells: (i) Oxyphilcells -> believed to play a role in stimulating the other cells to produce parathyroid hormone and to play a role in producing parathyroid hormone-related protein and vitamin D (ii) Chief cells -> primarily responsible for secreting parathyroid hormone (PTH)

Answer 37

There are specific genes expressed in the nucleus -> will be translated it into a protein -> a preform of parathyroid hormone The protein undergoes specific modifications and cleavage processes within the rough ER and Golgi apparatus -> turns into parathyroid hormone packaged into vesicles. The vesicles remain in the cell, ready to be released until the appropriate stimulus triggers them.

Answer 38

Hypocalcemia On the chief cells there are 7 pass transmembrane receptors, very sensitive to Ca++ When Ca++ levels are high -> calcium binds to these receptors -> triggers different intercellular processes and the overall effect of it is the inhibition of PTH release. If the Ca++ levels are low, there is less inhibitory input -> the vesicles containing PTH merge with the cell membrane -> PTH is released into the bloodstream.

Answer 39

Is stimulate by humoral stimuli, that could be: o Ions -> Ca++ in the case of PTH o Nutrients o Chemicals, etc. There are two other types of stimuli o Hormonal o Neural

Answer 40

The main structural unit of the thyroid gland -> follicular cells In between the follicles there is another type of cells -> parafollicular cells (aka C-cells) - Regulate calcium - Stimulated by high calcium blood levels - They work through calcium sensitive receptors (or also though calcium channels) -> the overall stimulus is hypercalcemia. Hypercalcemia -> stimulates the production of calcitonin packaged in vesicles -> The vesicles remain in the cell, ready to be released until the appropriate stimulus triggers them. High blood calcium levels stimulate the vesicles to fuse with the cell membrane and calcitonin is released into the bloodstream

Answer 41

Bone Kidneys

Answer 42

Two types of cells in the bones that regulate bone remodeling: o Osteoclasts -> responsible for bone resorption (breakdown the bone and the release the breakdown products in the blood. o Osteoblasts -> responsible for bone deposition (taking the required substance from the blood and depositing them into the bones). 2) On the osteoblasts there are receptors for PTH -> PTH binds to them -> the cell is stimulated to start secreting a specific chemical: RANK ligand 3) On the osteoclasts there are RANK-receptors. When RANK ligand binds to RANK receptors. The osteoclast becomes very active -> start secreting chemicals that will start breaking down some of components of the bones (collagen type 1, hydroxyapatite, calcium phosphate...) 4) A lot of Ca++ and PO43- are accumulated and released into the blood, increasing calcium and phosphate levels.

Answer 43

1) PTH affects the cells of the distal convoluted tubule (DCT) in the nephron 2) It activates a G stimulatory protein -> converts ATP to cAMP and cAMP activates protein kinase A 3) The activated pKA goes to the cell nucleus and stimulates specific genes -> produce specific proteins (packed into vesicles) -> calcium transport proteins 4) These proteins will be embed into the cellular membrane -> allow the Ca++ in the lumen of the DCT to flow into the cell, when normally the DCT is impermeable to ions (Na, Cl, Ca) and water. But Ca2+ cannot go out into the circulation as it would go against concentration gradient -> needs help. 5) There are sodium-potassium ATPases embedded in the membrane that pump 3Na+ outside and 2K+ inside the cells (primary active transport, requires ATP). 6) When there is a buildup of Na+ in the extracellular space, it goes into the cell down the concentration gradient (without using energy) -> this process helps Ca++ get out to the blood against its concentration gradient (secondary active transport) -> This leads to an increase in calcium concentration in the blood. At the same time phosphates are excreted in the form of PO43- or HPO42- -> they are part of the phosphate buffer system.

Answer 44

1) In the skin there is a specific chemical – INACTIVE precursor of vitamin D -> it is converted into cholecalciferol (CCF) when exposed to UV light, then it is released into the bloodstream and goes to the liver. 2) In the liver 25-hydroxylase will convert the CCF into 25-hydroxycholecalciferol and is released back into the blood. Then it goes to the kidneys. 3) In the kidneys, PTH affects specific tubular cells, increasing the expression of a specific enzyme -> 1-alpha-hydroxylase. - 25-hydroxycholecalciferol interacts with 1-alpha- hydroxylase -> produces 1,25-hydroxycholecalciferol (calcitriol, it is the ACTIVE form of vitamin D). - The produced calcitriol is released into the bloodstream and goes to the the duodenum (small intestine) 4) In the duodenum Vitamin D goes to the enterocytes and acts a steroid hormone -> asses through the cell membrane, binds to the intracellular receptor and stimulates a specific gene sequence -> produce specific proteins -> called calcium channel proteins. They help absorb more calcium from the gut lumen, and it is then released into the blood

Answer 45

1) Calcitonin is stimulated by high blood calcium levels -> its purpose is to lower them. It only affects the bones (changes the balance between osteoblastic and osteoclastic activity). 2) There are receptors for calcitonin directly onto the osteoclasts -> when calcitonin binds it sends signals to inhibit the osteoclast -> tips the balance towards osteoblastic activity (taking calcium from the blood and depositing it into the bone). 3) The osteoblasts also secrete other substances to complete bone deposition and make the bones thicker.

Answer 46

1) The adrenal glands sit on top of the kidneys -> also called suprarenal glands 2) Have a roughly pyramid shape 3) Parts of the adrenal gland Cortex - has three layers (all layers are mostly glandular cuboidal epithelial tissue) - Zona glomerulosa - most superficial - Zona fasciculata - in the middle, the thickest - Zona reticularis - the deepest Medulla -> has only one layer and is made up of neural tissue -> chromatin cells (cell bodies of the postganglionic neurons of the SNS.

Answer 47

1) Low blood pressure - The strongest STIMULUS of zona glomerulosa - Low blood pressure causes the juxtaglomerular cells in the kidneys produce renin. - The liver produces angiotensinogen -> renin acts on the angiotensinogen and converts it into angiotensin I. - In the lungs, angiotensin converting enzyme (ACE) converts angiotensin I into angiotensin II. - ATII goes to zona glomerulosa of the adrenal cortex and it activates a G stimulatory protein (adenylate cyclase 2nd messenger) -> converts ATP to cAMP o cAMP activates protein kinase A (pkA). 2) Hyponatremia / hyperkalemia - the second strongest STIMULUS of zona glomerulosa - Zona glomerulosa cells are very sensitive to hyponatremia and hyperkalemia. - ↓ Na+ levels and ↑ K+ levels exert a specific type of stimulus to synthesize aldosterone 3) ACTH - the weakest STIMULUS of zona glomerulosa. - The paraventricular nucleus in the hypothalamus secrete corticotropin-releasing hormone (CRH) -> goes to the anterior pituitary and stimulates the corticotrope cells in the adenohypophysis to secrete adrenocorticotropic hormone (ACTH) into the bloodstream. - ACTH goes to the adrenal cortex, binds to a g-protein coupled receptor, it activates a G stimulatory protein (adenylate cyclase) - converts ATP to cAMP that will activate protein kinase A. 4) Atrial natriuretic peptide (ANP) -> an INHIBITOR for the synthesis of aldosterone. Secreted when the blood pressure is high. Binds to specific receptors and activates a G inhibitory pathway. Results in potassium efflux out of the cell -> hyperpolarization of the cell -> alters enzymatic activity within the cholesterol pathway, resulting in inhibition of aldosterone production.

Answer 48

1) In the adrenal cortex steroid hormones are synthesized from cholesterol. Cholesterol is converted to corticosterone, and this to aldosterone -> each step in this pathway is regulated by specific enzymes. 2) The activated pkA (coming from all the stimuli previously mentioned) activates by phosphorylation the enzymes catalyzing this pathway on multiple steps. 3) Aldosterone is released into the bloodstream. It is a steroid hormone, therefore needs to bind to specific proteins for transportation -> mostly it binds to corticosteroid binding globulin (CBG, aka transcortin. Sometimes it binds to albumin).

Answer 49

Aldosterone goes to the the cells of the distal convoluted tubule of the nephron As a steroid hormone, aldosterone passes through the lipid bilayer of the cell membrane and binds to an intracytosolic receptor. The activated receptor activates 3 specific gene sequences, producing three different proteins: 1) Sodium-potassium ATPase -> pumps 3Na+ out and 2K+ into the cell. Utilizes ATP 2) Protein channels for Na+ into the luminal membrane -> bring Na+ from the filtrate into the cell and from the cell it goes into the blood -> water follows sodium -> increases blood volume, increases BP. 3) Protein channels for K into the luminal membrane -> move potassium that comes from the blood from the cell into the filtrate, to be lost in the urine (in response to the hyperkaliemia stimulus).

Answer 50

1) The paraventricular nucleus in the hypothalamus secrete corticotropin-releasing hormone (CRH). CRH goes to the anterior pituitary and stimulates the corticotropes cells in the adenohypophysis to secrete adrenocorticotropic hormone (ACTH) into the bloodstream. 2) ACTH (STRONG STIMULUS) goes to the adrenal cortex and binds to a g-protein coupled receptor, triggering an intracellular cascade -> G stimulatory protein -> cAMP -> pkA. 3) In the adrenal cortex steroid hormones are synthesized from cholesterol. Cholesterol is converted to progesterone, then to cortisol -> each step in this pathway is regulated by specific enzymes. 4) The activated pkA (produced after ACTH stimulation) activates by phosphorylation the enzymes catalyzing this pathway on multiple steps, leading to the formation of cortisol. 5) Cortisol it is a steroid hormone (lipid soluble), therefore needs to bind to specific proteins for transportation - Approx. ~75% binds to corticosteroid binding globulin (CBG, aka transcortin) - Approx. ~25% of it binds to albumin

Answer 51

1) Hypoglycemia is one of the main stimuli of cortisol. In response to it, cortisol will: o Indirectly stimulates glycogenolysis (by increasing the sensitivity of adrenergic receptors to norepinephrine). o Directly stimulates gluconeogenesis (the production of glucose from non-carbohydrate sources). o Directly stimulates glycogenesis (the conversion of glucose into glycogen). 2) Long term (chronic) stress is another stimulus -> causes a direct release of CRH -> excessive ACTH -> increased production of cortisol. In response cortisol will: o ↑ the sensitivity of adrenergic receptors for NE in the smooth muscle cells of the vessels -> vasoconstriction -> increased BP -> allows cells to get more nutrients. o ↑ muscle catabolism -> provides nutrients o Depresses the immune system

Answer 52

↑ levels of cortisol in the blood - Exert a negative feedback on the hypothalamus. - Inhibit the adenohypophysis production of ACTH. ↓ levels of cortisol in the blood - Not enough is going to the hypothalamus and the adenohypophysis to cause inhibition. - The hypothalamic nuclei are stimulated to produce more CRH -> the pituitary is stimulated to produce more ACTH -> synthesis of cortisol is stimulated.

Answer 53

As a steroid hormone cortisol passes through the lipid bilayer of the cell membrane, binds to an intracytosolic receptor and activates it. The activated receptor activates specific genes expressed in the nucleus -> translate it into proteins - PROTEASES. The proteases break the peptide bonds inside the muscle proteins -> produce amino acids that will be released into the bloodstream and go to the liver. The process is called protein CATABOLISM and it is stimulated by cortisol. Cortisol also stimulates catabolism within the bones.

Answer 54

Main component of the adipocytes -> triglycerides Cortisol passes through the lipid bilayer of the cell membrane and binds to an intracytosolic receptor, activating it. The activated receptor activates specific genes expressed in the nucleus and will be translate it into proteins. These proteins break down the triglycerides into fatty acids (utilized by the muscles or redistributed and relocated to different parts of the body) and glycerol (goes to the liver). This is called LIPOLYSIS.

Answer 55

Cortisol passes through the lipid bilayer of the cell membrane, binds to an intracytosolic receptor and activates it. The activated receptor activates specific genes expressed in the nucleus and will be translate it into proteins These proteins stimulate the processes of gluconeogenesis and glycogenesis. GLUCONEOGENESIS is a process where glucose is produced from non- carbohydrate sources (amino acids and lactic acid from the muscle, or glycerol / fatty acids coming from the adipose tissue). GLYCOGENESIS is a process where glucose is converted into glycogen (a storage molecule for glucose) Cortisol enhances the sympathetic nervous system -> acts on many different tissues sensitive to norepinephrine -> there are adrenergic receptors on the liver and they bind to NE, cortisol enhances the sensitivity of the G proteins to E/NE. The overall effect of norepinephrine on the vessels is glycogenolysis (conversion of glycogen into glucose). Therefore cortisol, directly stimulates glycogenesis (the conversion of glucose into glycogen), and indirectly stimulates glycogenolysis (the conversion of glycogen into glucose) by increasing the sensitivity of the adrenergic receptors for norepinephrine.

Answer 56

Cortisol enhances the sympathetic nervous system Acts on many different tissues sensitive to norepinephrine -> there are adrenergic receptors in the smooth muscle cells within the tunica media of the vessels (they bind norepinephrine). As a steroid hormone cortisol passes through the lipid bilayer of the cell membrane, binds to an intracytosolic receptor and activates it. The activated receptor activates specific genes expressed in the nucleus and will be translate it into proteins These proteins increase the sensitivity of the G protein-coupled adrenergic receptors of the cell -> the overall effect of norepinephrine on the vessels is vasoconstriction Cortisol amplifies the VASOCONSTRICTION.

Answer 57

Cortisol can inhibit specific processes inside the immune cells: o Basophils are responsible for secreting histamines, leukotrienes and prostaglandins o Lymphocytes and monocytes are responsible for secreting interleukins (IL1, IL2, IL4, etc.) and cytokines Cortisol inhibits the inflammatory immune response by preventing the immune cells from producing all those chemicals.

Answer 58

T1-L2, sympathetic outlflow

Answer 59

Short term stress (fight or flight)

Answer 60

The hypothalamus activates the SNS (very strong regulator) Has a sympathetic and a parasympathetic component and it sends presynaptic potential down through descending fibers to the lateral gray horn (LGH) of the spinal cord, between T1 to L2. In the LGH are located the bodies of the preganglionic motor neurons of the SNS- -> their axons come out through the ventral ramus and move through sympathetic chain ganglia, all the way to the adrenal medulla. REMEMBER: In most cases, SNS preganglionic neurons -short -> go to the chain ganglia -> postganglionic neurons are long (they begin from the chain ganglia). The ADRENAL MEDULLA is an EXCEPTION -> preganglionic motor neurons are long -> reach the postganglionic cell bodies -> postganglionic cell neurons are very short -> cell bodies located inside the actual organ (adrenal medulla) -> called an intramural ganglion.

Answer 61

- SNS preganglionic motor neurons are cholinergic -> they release acetylcholine, that binds to nicotinic receptors on the chromaffin cells. - Cations (e.g. Na+) flow in and activate specific action potentials, stimulating certain processes within the cell. - The depolarization of the cell activates certain enzymes (a specific biochemical pathway is triggered) - Tyrosine is the building block of this pathway -> will be converted to dopamine - Dopamine is converted to norepinephrine (by dopamine betahydroxylase) - Norepinephrine is converted to epinephrine.

Answer 62

The synapse of the axon of the postganglionic motor neurons secretes 80% epinephrine and 20% norepinephrine. Normally epinephrine and norepinephrine are presynthesized, put into vesicles and located in the terminal bulb of the axon. When Na+ enters the cell -> action potential -> travel down the axon and when they reach the terminal bulb -> Ca++ channels located there, open -> Ca++ starts flowing in and acts as a bridge. Causes the vesicles to merge with the cell membrane and epinephrine and norepinephrine are released into the bloodstream.

Answer 63

Liver Adipose tissue Heart Respiratory system Blood vessels going to GI tract, kidneys and skin.

Answer 64

Epinephrine goes to the liver and binds to a G protein-coupled receptor -> activates a G stimulatory protein (adenylate cyclase -> convert ATP to cAMP, cAMP activates pkA). Glycogenolysis -> there is about 300g of glycogen in the liver -> enzymes (glycogen phosphorylase, debranching enzymes, etc.) cut up the glycogen into individual monomers (glucose). The process is stimulated by catecholamines (cortisol increases the sensitivity of the adrenergic receptors to catecholamines). Gluconeogenesis -> a process where non-carbohydrate sources are turned into glucose (amino acids and lactic acid form the muscles, glycerol and odd chain fatty acids from the adipose tissue) The overall result of both glycogenolysis and gluconeogenesis is increased blood glucose The glucose can be utilized by the muscles for contraction

Answer 65

Catecholamines bind to a G protein-coupled receptor and activated the enzyme hormone sensitive lipase (HSL) -> breaks down triglycerides into fatty acids and glycerol. The glycerol then goes to the liver and gets converted to glucose The fatty acids go to the muscles and undergo beta oxidation and produce ATP (helps with contraction).

Answer 66

On the cardiomyocytes: Stimulates the expression of B1-adrenergic receptors -> they bind catecholamines -> increase contractility -> increased stroke volume -> increased CO -> increased BP. Non-contractile muscle cells of the SA node and the AV node: Stimulates the expression of B1-adrenergic receptors, that bind catecholamines -> increased action potentials -> increased HR -> increased CO -> increased BP. Catecholamines also bind to alpha-1-adrenergic receptors on some blood vessels -> cause vasoconstriction -> decreases lumen diameter -> increased vascular resistance -> increased BP. Increases in blood pressure will get more nutrients to the vital tissues and faster.

Answer 67

Smooth muscle surrounds the bronchi -> catecholamines act on those smooth muscle cells by binding to B-2-adrenergic receptors -> cause the bronchioles to dilate. If they dilate -> more air into respiratory system -> increases oxygen going into the lungs and amount of CO2 being exhaled.

Answer 68

The vessels going to the GI tract constrict and divert the blood to skeletal muscles, brain, heart, etc. Therefore catecholamines ↓ GI tract activity. The blood vessels going to the kidneys constrict and divert the blood. The blood vessels in the skin constrict and divert the blood.

Answer 69

- Endocrine function -> from Islets of Langherans (alpha, beta, delta, pp and epsilon cells) - Exocrine (digestive) functions -> from pancreatic acini

Answer 70

B cells Alpha cells

Answer 71

Beta cells Delta cells

Answer 72

Secreted in response to increased energy-giving foods in the diet: - Glucose - Amino acids - Gastrin, secretin, CCK, glucose-dependent insulinotrophic peptide - Glucagon, growth hormone, and cortisol (prolonged excessive increased cortisol leads to beta cell exhaustion -> leads to diabetes mellitus)

Answer 73

The iodide (i-) pump, or Na+-I- cotransport

Answer 74

5'-iodinase

Answer 75

Atrial Natriuretic peptide

Answer 76

cholesterol desmolase pregnenolone

Answer 77

In normal persons, low-dose dexamethasone inhibits or "suppresses" ACTH secretion and, consequently, cortisol secretion. In persons with ACTH-secreting tumors, low-dose dexamethasone does not inhibit cortisol secretion but high-dose dexamethasone does. In persons with adrenal cortical tumors, neither low- nor high-dose dexamethasone inhibits cortisol secretion.

Answer 78

Lipocortin

Answer 79

1. induce the synthesis of lipocortin, an inhibitor of phospholipase A, 2. inhibit the production of IL-2 3. inhibit the proliferation of T lymphocytes. 4. Inhibit the release of histamine from mast cells 5. inhibit the release of serotonin from platelets.

Answer 80

Glucocorticoids inhibit the production of IL-2 and T lymphocytes

Answer 81

progesterone, deoxycorticosterone, aldosterone, and cortisol. C-21 C-17

Answer 82

Glut 2 Potassium Calcium intracellular [Ca2+]

Answer 83

Is a tetramer, with two alpha subunits and two beta subunits. a. The alpha subunits are located on the extracellular side of the cell membrane. b. The beta subunits span the cell membrane and have intrinsic tyrosine kinase activity.

Answer 84

Somatostatin

Answer 85

E. Thyroid-stimulating hormone (TSH) is secreted by the anterior pituitary. Dopamine, growth hormone-releasing hormone (GHRH), somatostatin, and gonadotropin-releasing hormone (GnRH) all are secreted by the hypothalamus. Oxytocin is secreted by the posterior pituitary. Testosterone is secreted by the testes.

Answer 86

A)Thyroid hormone, an amine, acts on its target tissues by a steroid hormone mechanism, inducing the synthesis of new proteins. The action of antidiuretic hormone (ADH) on the collecting duct (V2 receptors) is mediated by cyclic adenosine monophosphate (cAMP), although the other action of ADH (vascular smooth muscle, V1 receptors) is mediated by inositol1,4,5-triphosphate (IP3). Parathyroid hormone (PTH), beta 1 -agonists, and glucagon all act through cAMP mechanisms of action.

Answer 87

The answer is D. Growth hormone is secreted in pulsatile fashion, with a large burst occurring during deep sleep. Growth hormone secretion is increased by sleep, stress, puberty, starvation, and hypoglycemia. Somatomedins are generated when growth hormone acts on its target tissues; they inhibit growth hormone secretion by the anterior pituitary, both directly and indirectly (by stimulating somatostatin release).

Answer 88

The answer is A. Aldosterone is produced in the zona glomerulosa of the adrenal cortex because that layer contains the enzyme for conversion of corticoste- rone to aldosterone (aldosterone synthase). Cortisol is produced in the zona fasciculata. Androstenedione and dehydroepiandrosterone are produced in the zona reticularis. Testosterone is produced in the testes, not in the adrenal cortex.

Answer 89

The answer is C. The conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (as well as the conversion of 17-hydroxyprogesterone to androstenedione) is catalyzed by 17,20-lyase. If this process is inhibited, synthesis of androgens is stopped.

Answer 90

The answer is E deficiency (low caz.. diet or hypocalcemia) activates !a-hydroxylase, which catalyzes the conversion of vitamin D to its active form, 1,25-dihy- droxycholecalciferol. Increased parathyroid hormone (PTH) and hypophosphatemia also stimulate the enzyme. Chronic renal failure is associated with a constellation of bone diseases, including osteomalacia caused by failure of the diseased renal tissue to produce the active form of vitamin D.

Answer 91

The answer is A, Addison disease is caused by primary adrenocortical insufficiency. The resulting decrease in cortisol production causes a decrease in negative feedback inhibition on the hypothalamus and the anterior pituitary. Both of these conditions will result in increased adrenocorticotropic hormone (ACTH) secretion. Patients who have adrenocortical hyperplasia or who are receiving exogenous glucocorticoid will have an increase in the negative feedback inhibition of ACTH secretion.

Answer 92

E) Gonadotropin-releasing hormone (GnRH)

Answer 93

The answer is A. The conversion of cholesterol to pregnenolone is catalyzed by cholesterol desmolase. This step in the biosynthetic pathway for steroid hormones is stimulated by adrenocorticotropic hormone (ACTH).

Answer 94

The answer is A. Decreased blood volume stimulates the secretion of renin (because of decreased renal perfusion pressure) and initiates the renin-angiotensin-aldo- sterone cascade. Angiotensin-converting enzyme (ACE) inhibitors block the cascade by decreasing the production of angiotensin II. Hyperosmolarity stimulates antidiuretic hormone (ADH) (not aldosterone) secretion. Hyperkalemia, not hypokalemia, directly stimulates aldosterone secretion by the adrenal cortex.

Answer 95

The answer is B. Parathyroid hormone (PTH) stimulates both renal Ca2+ reabsorption in the renal distal tubule and the 1a-hydroxylase enzyme. PTH inhibits (not stimulates) phosphate reabsorption in the proximal tubule, which is associated with an increase in urinary cyclic adenosine monophosphate (cAMP). The receptors for PTH are located on the basolateral membranes, not the luminal membranes.

Answer 96

The answer is A. The insulin receptor in target tissues is a tetramer. The two J3 subunits have tyrosine kinase activity and autophosphorylate the receptor when stimu- lated by insulin.

Answer 97

1. Severe PU/PD (ex. Cushings, aggressive IV fluid therapy) 2. The solutes necessary to produce the medullary hypertonicity gradient are lacking, such as insufficient urea in dogs and cats with hepatic insufficiency or insufficient sodium in dogs with hypoadrenocorticism.

Answer 98

Hyposthenuric

Answer 99

The most likely remaining causes of the severe polyuria and polydipsia in this dog are hyperadrenocorticism, CDI or NDI, and primary or psychogenic polydipsia. Additional diagnostics: - low dose dex. Suppresion test for cushing's (or urine cortisol/creat ratio) - Serum osmolality (if <280mOsm/L --> suspect psycogenic polydipsia / if 280 or more --> grey zone) - Modified water deprivation test - Desmopressin acetate trial

Answer 100

Theoretically the dogs with primary or psychogenic polydipsia should always be slightly overhydrated (with a low serum sodium concentration and low serum osmolality), and dogs with other causes of polyuria and polydipsia including diabetes insipidus should be slightly dehydrated (with a relatively high serum sodium concentration and serum osmolality) why? because in primary polydipsia dogs drink excessively and as a consecuence of the polydipsia they become polyuric. In other causes (Cushings, DI), patient urinates excessively and as a consecuence becomes polydipsic On a random serum osmolality assay a result of less than 280 mOsm/L would be most consistent with psychogenic polydipsia.

Answer 101

Is based on the premise that a dog that truly suffers from diabetes insipidus will not be able to concen- trate its urine even under conditions of moderate dehydration. This is because of either a lack of vasopressin (CDI) or lack of an appropriate renal response to vasopressin (NDI). An appropriate rise in urine specific gravity while dehydrated would be suggestive of psychogenic polydipsia. If not appropiate rise in USG after dehydration --> CDI vs NDI? --> Desmopressin given IM: marked increase in USG --> CDI Complete lack of response --> suggestive of NDI

Answer 102

Medullary washout If the medullary interstitium has been “washed out” of solutes because of chronic severe polyuria and polydipsia for any reason, no urine concentration will occur despite the presence of endogenous vasopressin, desmopressin, and intact renal V2 receptors. These dogs are then mistakenly diagnosed as suffering from NDI. The modified water deprivation test protocol attempts to eliminate this problem by recommending mild water restriction for a number of days before the test.

Answer 103

Pulmonary tumors that ectopically produce ADH Diseases that interrupt the inhibitory impulses in vagal afferents from stretch receptors in the atria and great veins.

Answer 104

FALSE - Most cases of hyponatremia, hyposmolality, and hypovolemia are associated with an elevated ADH concentration, regardless of the cause.

Answer 105

Methimazole inhibits iodine incorporation into thyroglobulin and thus prevents the synthesis of active thyroid hormone it does not prevent the secretion of already formed thyroid hormones

Answer 106

stable iodine compounds such as potassium iodide

Answer 107

The β-adrenergic receptors Propranolol and atenolol

Answer 108

Propranolol inhibits the peripheral conversion of T4 to T3

Answer 109

Rottweiler

Answer 110

Non-regenerative anemia Thyroid hormones bind thyroid hormone receptors on erythroid progenitors and act directly to increase erythroid proliferation. Thyroid hormones also increase expression of the erythropoietin gene, further contributing to red blood cell formation

Answer 111

Tyrosine hydroxylase

Answer 112

FALSE - In dogs 65% to 83% of pheochromocytomas are detected via abdominal ultrasonography, making it a useful first-line imaging modality.

Answer 113

Pheochromocytomas seem to have a higher likelihood for vena caval invasion than do adrenocortical tumors (ultrasonographically both can look very similar).

Answer 114

Urinary normetanephrine to creatinine ratio

Answer 115

a. alpha-blockers --> phenoxybenzamine 0.6mg/kg PO q12h for 20 days before surgical removal decreased mortality by 48 to 13% of patient undergoing adrenalectomy Use of beta-blockers is not reported in veterinary pheochromocytoma patients and should be initiated only after alpha-blockade is achieved.

Answer 116

50% 18-31%

Answer 117

Renal hypoperfusion, JG cells hypoperfusion Renin secreting tumors *rare --> primary hyperaldosteronism is more common (cats)

Answer 118

FALSE --> despite an absolute increase in total body sodium, these patients appear normonatremic due to water retention * most cats with PHA will have a normal sodium but are typically hypokalemic.

Answer 119

Amlodipine besylate 0.625mg/kg PO q24h Potassium supplementation (K gluconate 2mEq/cat q12h) Spironolactone 2mg/kg q12h

Answer 120

~85% of cases pituitary adenoma (micro or macro adenomas) ~15% of cases functional adrenal tumors (1/2 of the time are malignant)

Answer 121

GI disease Parasitism (trichuris vulpis) Third spacing CHF Diabetes Mellitus

Answer 122

Because usually azotemia is pre-renal but there is medullary washout secondary to the hyponatremia which decreases USG.

Answer 123

Opioids, etomidate, azole antifungals, benzodiazepines

Answer 124

Equal or <0.3ug/dL

Answer 125

The primary findings of CORTICUS were that low-dose hydrocortisone treatment led to more rapid pressor weaning regardless of ACTH stimulation test results, that hydrocortisone had no survival benefit despite more rapid pressor weaning, and that hydrocortisone treatment was associated with more incidents of superinfection than placebo * Limitations : small sample size, study population was less severely ill and its control group mortality was lower than that of the French study.

Answer 126

Cytoplasmic enzyme that has the capability to convert inactive cortisone to active cortisol, and under some conditions, to convert active cortisol to inactive cortisone --> active cortisol then binds to the GR receptor --> this complex moves to the nucleus to exerst genomic effects and alter protein production and cell function

Answer 127

FALSE - they recommend AGAINST

Answer 128

To help avoid hyperglycemic episodes

Answer 129

Dexamethasone is highly structurally altered from the parent cortisol molecule and may therefore carry excessive immunosuppressive effects without the benefit of hydrocortisone’s modest mineralocorticoid effect.

Answer 130

0.5 mg/kg hydrocortisone IV every 6 hours or 0.08 mg/kg/hr as a constant rate infusion

Answer 131

Toll like receptors --> specially TLR-2 and TLR-4 in the adrenal cortex itself

Answer 132

FALSE - is is produced from cholesterol but minimal cortisol is stored and thus increased cortisol production during stress relies almost entirely on cortisol synthesis

Answer 133

TRUE - the enzymes are CYP11B1 and CP11B2

Answer 134

Exocrine part - made up of Acini 99% of the pancreas volume Release pancreatic juice Rich in digestive enzymes and bicarbonates Endocrine part - made up of Islets of Langerhans 1% of the pancreas volume Different cells: o Alpha cell -> produce glucagon o Beta cells -> produce insulin o Delta cells -> produce somatostatin o F cells (PP cells) -> produce pancreatic polypeptide hormone

Answer 135

1) Secretion -> glucagon GlucAgon is secreted by the Alpha cells. 2) Stimuli Low blood glucose levels -> below 70-80 mg/dl Glucagon is secreted when glucose is Gone. Sympathetic nervous system hormones o Epinephrine o Norepinephrine Hormones produced by the intestine o Cholecystokinin o Secretin 3) Effects -> increases the blood glucose levels Liver o Gluconeogenesis (glycerol, amino acids, etc. get converted to glucose) o Glycogenolysis (glycogen gets broken down to glucose) Adipose tissue o Lipolysis (triacylglycerol (TAG) gets broken down to fatty acids and glycerol)

Answer 136

1) Secretion - insulin 2) Stimuli -> high blood glucose levels o Above 120-130 mg/dl 3) Effects - decreases the blood glucose levels Liver o Glycogenesis o Minor ↑ protein synthesis o Minor ↑ amino acid uptake Adipose tissue o Lipogenesis o ↑ glucose intake via GLUT-4 Muscles o ↑ glucose intake via GLUT-4 o ↑ amino acids intake o ↑ protein synthesis o Minor glycogenesis

Answer 137

1) Antagonism -> hormones that have opposing effects -> glucagon and insulin 2) Synergism -> hormones that have the same effect -> epinephrine and norepinephrine 3) Permissiveness -> when one hormone needs to be present in order for another hormone to function -> thyroid hormone is required for certain types of sex hormones to cause brain development.

Answer 138

Glucose transporters type 2, that are insulin independent

Answer 139

Inside the DNA of ß-cells there is a specific gene that undergoes transcription and gets converted specific protein The protein goes to the rough endoplasmic reticulum and undergoes modifications Then it goes to the Golgi apparatus where it gets packaged Out of the Golgi come vesicles with fully packaged insulin, C-peptide and amylin.

Answer 140

1) Beta cells respond to hyperglycemia -> in the cell membrane there are Glucose transporters type 2 (GLUT2), that are insulin independent. 2) Glucose enters the cell and undergoes glycolysis, producing ATP. 3) There are K+ channels on the cell membrane that bind that ATP -> this closes them and K+ ions are accumulated as they cannot leave the cell. 4) These are positively charged ions -> increases the positive membrane potential, stimulating Ca++ channels -> influx of Ca++ 6) Influx of Ca++ causes the vesicles and the membrane to fuse and insulin, c-peptide and amylin go into the blood.

Answer 141

Liver Adipose tissue Muscles

Answer 142

1) Insulin binds to a tyrosine kinase receptor - This way it stimulates phosphorylation of tyrosine residues -> an intracellular messenger is activated (PI3K / AKT). - In the liver there are GLUT-2 receptors -> same as the beta cells (insulin independent) -> glucose moves in at a constant rate 2) Insulin takes effect once glucose is in the liver (via GLUT2 transporters) Glycogenesis (glucose is polymerized to glycogen) Glycolysis -> convert glucose into pyruvate, blablabla) -> ATP is produced

Answer 143

1) Insulin binds to a tyrosine kinase receptor -> stimulates phosphorylation of tyrosine residues -> the intracellular messenger – PI3K/AKT is activated 2) PI3K/AKT activates GLUT- 4 receptors (insulin dependent) and increases glucose intake. 3) Inside the cell - Glycolysis -> ATP is produced - PI3K/AKT increases amino acid intake -> stimulates the amino acid channels (during the ‘fed’/absorptive state the blood levels of amino acids are high). - PI3K/AKT stimulates the protein synthesis from amino acids. - PI3K/AKT converts glucose into glycogen in the muscles.

Answer 144

1) Insulin binds to a tyrosine kinase receptor - PI3K/AKT is activated -> activates GLUT-4 receptors (insulin dependent) -> increased glucose intake 2) Lipogenesis Inside the cell, glucose splits into o Glyceraldehyde 3-phosphate (G3P) (eventually forms pyruvate and acetyl CoA) o Dihydroxyacetone phosphate (DHAP) Insulin stimulates o Conversion of DHAP into glycerol o Conversion of acetyl CoA into fatty acids -> glycerol and fatty acids are combined into triacylglycerol (TAG, aka tryglycerides) – lipogenesis Insulin also stimulates the intake of fatty acids

Answer 145

Inside the DNA of α-cells there is a specific gene -> undergoes transcription and gets converted into a specific protein - proglucagon. Proglucagon goes to the rough endoplasmic reticulum and undergoes modifications and becomes glucagon. Then it goes to the Golgi apparatus where it gets released in vesicles with fully packaged glucagon.

Answer 146

Alpha cells respond to HYPOGLYCEMIA (main stimulus). In the cell membrane there are specific transporters (GLUT-1 - insulin independent) Glucose enters the cell and undergoes glycolysis - produces ATP. There are K+ channels on the cell membrane that bind to ATP -> it closes them When there is less incoming glucose → ↓ produced ATP -> less ATP binds to the channels -> the channels still close, but not very tight -> some K+ ions are still being blocked from exiting -> the cell is less positive -> less membrane depolarization -> calcium channels open up, leading to influx of calcium. If there is more incoming glucose → ↑ produced ATP -> large amounts of ATP bind to the channels -> they close very tight -> lots of K+ remain in the cell -> become extremely positive -> membrane depolarization -> the calcium channels close, therefore Ca++ can’t come in.

Answer 147

Liver Adipose tissue Myocardium

Answer 148

- Glucagon activates a G stimulatory protein (adenylate cyclase 2nd messenger -pkA activation) - Glycogenolysis -> the activated pkA stimulates the enzyme glycogen phosphorylase to convert glycogen into glucose. - Gluconeogenesis -> activated pkA phosphorylates enzymes that converts glycerol, amino acids and fatty acids into glucose - Glucose is released into the blood and elevates the glucose blood levels.

Answer 149

Glucagon activates a G stimulatory protein (adenylate cyclase 2nd messenger) -> activates protein kinase A. The activated pKA phosphorylates different enzymes, like the hormone sensitive lipase (HSL) -> breaks the ester bonds that hold triacylglycerol (TAG) together -> two products glycerol (goes to the liver to undergo gluconeogenesis) and fatty acids -> LIPOLYSIS.

Answer 150

Glucagon activates a G stimulatory protein -> adenylate cyclase 2nd messenger -> activates pkA. - The activated pKA activates and opens up specific Ca++ channels. - The elevated Ca++ levels increase the contractility of the heart -> ↑ stroke volume -> ↑ cardiac output -> ↑ blood pressure Glucagon is a POSITIVE INOTROPIC agent

Answer 151

Acetyl Co-enzyme A, which is a byproduct of mitochondrial fatty acid oxidation

Answer 152

Conversion of glucose to glycogen, storage of amino acids as protein and storage of fatty acids in adipose tissue

Answer 153

Glycogenolysis, proteolysis, lipolysis

Answer 154

Under normal conditions, the acetyl CoA that is produced during lipolysis enters the citric acid cycle along with pyruvate (from glycolysis). However, in diabetes, there is not much pyruvate, and as such, the citric acid cycle is slowed down. Acetyl CoA is therefore not used for ATP production and accumulates.

Answer 155

Beta hydroxybutyrate, acetoacetate, acetone. Acetoacetate is made from AcetylCoA, and then can be converted into acetone or BHB Liver

Answer 156

Glucagon, epinephrine, cortisol, somatotropic hormone

Answer 157

IL 18, resistin, GMCSF (granulocyte-monocyte colony stimulating factor), keratinocyte chemoattractant, IL 8, monocyte chemoattractant protein 1.

Answer 158

Dogs: 8 years Cats: 9 years

Answer 159

Dogs: 70% Cats: 90%

Answer 160

Dogs: Pancreatitis, UTI, Cushing’s Cats: Acute pancreatitis, hepatic lipidosis, CKD, infections (bacterial or viral), neoplasia

Answer 161

Heinz body formation

Answer 162

Initially: hyperkalemia (decreased renal excretion, hypoinsulinemia, acidosis), but whole body depletion. With rehydration: Hypokalemia (osmotic diuresis, binding to ketoacids)

Answer 163

Whole body depletion, similar mechanisms to K; P shifts to extracellular space Later: hypophosphatemia

Answer 164

Hemolysis, seizures Weakness, myocardial depression, arrhythmias

Answer 165

Ionized hypomagnesemia, hyponatremia, hypochloremia, ionized hypocalcemia

Answer 166

Hypertension, insulin resistance, hyperlipidemia and increased platelet aggregation

Answer 167

Pseudohyponatremia Increased water intake due to diuresis, increased ADH secretion

Answer 168

Urine or serum sample Urine dipstick: Nitroprusside reagent reacts with acetoacetate, but not with BHB, which is the dominant ketone in dogs and cats.

Answer 169

Acute pancreatitis, chronic starvation, chronic hypoglycemia, low carb diet, pregnancy, persistent fever

Answer 170

Fluid therapy first to restore intravascular volume, rehydration. This alone will lower blood glucose levels. (Theory: by restoring renal perfusion, thexpression of counterregulatory hormones is decreased) Electrolyte correction Start insulin (after about 6 hours) -> paper on early insulin: no detrimental effects on starting early vs late.

Answer 171

0.03-0.12 mmol/kg/h

Answer 172

Regular insulin as CRI -> measure glucose q 2 h Regular insulin IM q1h -> measure glucose q 1 h: Start with a dose of 0.2 U/kg IM, then give 0.1 U/kg IM one hour later. Then give insulin depending on how fast the glucose drops: If glucose drops less than 50 mg/dl -> give 0.2 U/kg IM If glucose drops between 50 and 75 mg/dL, give 0.1 IU/kg IM If glucose drops by more than 75 mg/kg -> give 0.05 IU/kg IM Glargine protocols: IM and SQ

Answer 173

Dogs: 2.2 IU/kg/d Cats: Previous recommendation 1.1 U/kg/day, but using the dog dose was not associated with complications in cats in a recent study.

Answer 174

If the pH remains below 7 after 1 hour of fluid therapy.

Answer 175

CSF acidosis, brain edema, exacerbation of hypokalemia, increased hepatic ketone production.

Answer 176

Concurrent hyperadrenocorticism and degree of base deficit

Answer 177

Complication of diabetes characterized by no or minimal ketones, severe hyperglycemia (> 600 mg/dL) and hyperosmolarity (> 350 mosmol/L).

Answer 178

Hormonal alterations, decreased GFR, concurrent disease.

Answer 179

Complete or partial lack of insulin, combined with increased concentrations of counterregulatory hormones

Answer 180

HHS is believed to have small amounts of insulin as well as hepatic glucagon resistance, so that there is less lipolysis -> none or almost no ketone production.

Answer 181

Hypernatremia, elevated BUN levels, acidemia, osmolality. NOT the level of hyperglycemia

Answer 182

CKD, CHF, infection, neoplasia, other endocrinopathies

Answer 183

Osmolality = 2x Na + Glucose (mg/dL)/18 + BUN (mg/dL)/2.8

Answer 184

Effective osmolality = 2xNa + Glucose (mg/dL)/18

Answer 185

Corrected Na = Measured Na + 1.6 [(measured glucose – normal glucose)/100]

Answer 186

Uremic acids and lactic acid

Answer 187

Compounds stored in neurons in states of blood hyperosmolality. This prevents cerebral dehydration. If the serum glucose is decreased too quickly, there is not enough time for the body to eliminate these, and cerebral edema may occur.

Answer 188

Normal saline, because the Na replaces the glucose -> prevention of rapid shifts in osmolality.

Answer 189

Not as important as in DKA. Should only be started once normal intravascular status has been achieved, the dehydration has improved and glucose levels are no longer falling adequately (i.e. > 50 mg/dL/h) with fluid therapy alone.

Answer 190

50-75 mg/dL/h

Answer 191

Regular insulin at the lower dose: 1 IU/kg into 250 ml of NaCl instead of 2.2 Regular insulin IM: 0.05-0.1 IU/kg q 2-4h

Answer 192

Dogs: 38% Cats: 65%

Answer 193

Not well established. In one canine study: low venous pH, abnormal mental status

Answer 194

a. Intestinal absorption from digestion of carbohydrates b. Breakdown of the storage for of glucose (glycogen) via glycogenolysis c. Production of glucose from precursors lactate, pyruvate, amino acids, and glycerol via gluconeogenesis

Answer 195

Lowering: insulin Elevating: glucagon, epinephrine, cortisol and growth hormone

Answer 196

a. Secreted by B-cells of the pancreas in response to rising concentrations of glucose, amino acids and GI hormones presents after a meal (gastrin, secretin, cholecystokinin and gastric inhibitory peptide) b. Effects: i. Inhibits gluconeogenesis and glycogenolysis ii. Promotes glycogen storage iii. Stimulates glucose uptake and utilization by insulin-sensitive cells iv. Decreases glucagon secretion v. Promotes triglyceride formation in adipose tissue vi. Promotes synthesis of protein and glycogen in muscle vii. Decreased levels of insulin stimulate gluconeogenesis and reduce glucose used by peripheral tissues.

Answer 197

a. Glucagon and epinephrine b. Rise within minutes of hypoglycemia c. Transient effect

Answer 198

a. Cortisol and growth hormone. b. Longer lasting effects.

Answer 199

a. Secreted from pancreatic alpha cells b. Effects i. Increases hepatic glucose production => acts on the liver to stimulate glycogenolysis and to a lesser extent, gluconeogenesis. ii. Transient effect iii. Mobilizes gluconeogenic precursors iv. Reduces peripheral glucose utilization

Answer 200

a. Limits insulin secretion b. Increases glucagon secretion

Answer 201

Increases glucose-facilitating lipolysis and release of amino acids from muscle for gluconeogenesis in the liver

Answer 202

Antagonizes effects of insulin by decreasing peripheral glucose utilization and promoting lipolysis.

Answer 203

a. Inadequate dietary intake b. Excessive glucose utilization c. Dysfunctional glycogenolytic or gluconeogenic pathways or inadequate precursors for these pathways d. Endocrine abnormalities

Answer 204

a. Limited ability to use other substrates as energy source b. Can store minimal amounts of glycogen c. Cannot manufacture glucose

Answer 205

Hypoglycemia of the central nervous system

Answer 206

Altered mentation/dullness, sleepiness, weakness, recumbency, ataxia, blindness, altered vision, seizures.

Answer 207

Prolonged neuroglycopenia can lead to permanent brain injury and neurological signs, especially blindness, that can persist beyond resolution of the hypoglycemia.

Answer 208

<60mg/dL but often signs are not seen until BG <50mg/dL.

Answer 209

A collection of 3 criteria that suggest a patient’s symptoms are due to hypoglycemia i. Clinical signs consistent with hypoglycemia ii. Low blood glucose levels iii. Relief of symptoms when glucose levels are raised.

Answer 210

Because the RBCs will continue to consume glucose for glycolysis.

Answer 211

a. Cats b. Obese animals c. Cats receiving >6IU / injection

Answer 212

a. Evaluating blood insulin concentrations on a sample taken during an episode of hypoglycemia. b. High or normal levels of insulin in face of hypoglycemia are indicative of insulinoma.

Answer 213

a. Is used when the insulin levels are equivocal. b. AIGR = (insulin x 100) / (plasma glucose – 30) c. If plasma glucose is <30 then a denominator of 1 is used.

Answer 214

Surgical excision + medical management.

Answer 215

Because approximately 50% of the patients have metastatic disease evident at surgery and the majority of the others have occult metastases.

Answer 216

a. Dietary management: small, frequent feedings of a food low in simple sugars b. Glucocorticoids c. Diazoxide => directly inhibits pancreatic insulin secretion – can be used in patients with refractory disease d. Streptozocin – selectively destroys pancreatic B cells e. Somatostatin analogs such as octreotide – suppresses synthesis and secretion of insulin f. Alloxan – B cell cytotoxin

Answer 217

Biomarker Ki67 index – last paper on 2010?

Answer 218

a. Hepatomas and hepatocellular carcinoma b. Leiomyomas and leiomyosarcomas c. Other carcinomas or adenocarcinomas (especially those of pulmonary, mammary and salivary origin) d. Lymphoma e. Plasmacytoid tumors f. Oral melanoma g. Hemangiosarcoma

Answer 219

a. Secretion of insulin or insulin-like peptides b. Accelerated consumption of glucose by the tumor cells c. Failure of glycogenolysis or gluconeogenesis by the liver

Answer 220

Sulfonylurea drugs chloropropamide and glipizide

Answer 221

a. Stimulates insulin release from pancreatic B cells b. Can cause hepatic necrosis and failure, leading to hypoglycemia.

Answer 222

Interfering with adrenergic counterregulatory mechanisms.

Answer 223

a. Inadequate substrate for glycolysis or gluconeogenesis b. Glycogen stores are small and easily depleted in face of inadequate food intake c. Hepatic enzymes systems may also be immature.

Answer 224

Premature birth, debilitation of the bitch or queen at parturition, being the runt of the litter and diabetes in the bitch

Answer 225

a. PSS, glycogen storage disease, severe inflammatory or infectious hepatitis, hepatic lipidosis, cirrhosis, hepatic neoplasia and toxicity. b. Lead to hypoglycemia via dysfunctional glycogen storage, glycogenolytic and gluconeogenic capabilities.

Answer 226

Approximately 70%

Answer 227

Via loss of cortisol-induced counterregulatory mechanisms.

Answer 228

a. Decreased intake b. Decreased hepatic function c. Most significantly: non-insulin-mediated increased consumption => due to inflammatory mediators (TNF, especially in macrophage-rich tissues such as the spleen liver and lungs) d. Hypotension/hypoxemia may also induce excess glucose consumption (increases in anaerobic glycolysis).

Answer 229

Canine babesiosis

Answer 230

Hunting dog hypoglycemia

Answer 231

It is believed to occur secondary to glycogen depletion in the face of increased glucose utilization

Answer 232

a. Secondary to increased metabolism of glucose by the large RBCs mass (same with leukocytes) b. No.

Answer 233

a. Dextrose 50% bolus – 0.5-1mL/kg IV slow diluted 1:2-1:4 over 5 minutes b. If no IV: karo Syrup or honey on gums c. If mentally normal: small meals d. Dextrose CRI: 2.5% or 5% - if higher then needs to be given through central line.

Answer 234

It will cause hyponatremia that can be severe

Answer 235

a. A bolus of IV dextrose can stimulate release of even more insulin from the tumor leading to a vicious cycle and rebound hypoglycemia. b. Hyperinsulinemia has been shown to depress glucagon secretion in humans – we are removing one of the counterregulatory mechanisms. c. Small meals if mentation is appropriate d. Glucagon CRI in animals with insulin or insulin like peptide-secreting tumors that are in a refractory hypoglycemic crisis. e. Glucocorticoids (prednisone / dexamethasone).

Answer 236

a. By a lack of vasopressin b. Lack of renal receptors to vasopressin c. Or inability of those receptors to respond to vasopressin

Answer 237

a. ADH, antidiuretic hormone b. Arginine vasopressin – is a peptide with 9 amino acids, and the 8th is arginine

Answer 238

It will remain hyposthenuric or can be isosthenuric (or mild hypersthenuric with partial disease) after Na (and subsequently Cl) have been actively extracted from the solute area that is impermeable to water in the ascending loop of Henle.

Answer 239

Secreted in the supraoptic nuclei of the hypothalamus Stored in the posterior lobe of the hypophysis (pituitary gland)

Answer 240

a. Plasma osmolality – increases in ECF Osm are detected by osmorreceptors on the hypothalamus and lead to a rapid increase in ADH b. Effective circulating volume – will cause CV reflexes. Low-pressure baroreceptors of the cardiac atria and high-pressure baroreceptors of the aortic arch and carotid sinus stimulate vasopressin release in response to a decrease in BP or blood volume. c. Angiotensin II will act on angiotensin II receptors on the hypothalamus and cause ADH release d. Release of ADH is more sensitive to changes in osmolality than in ECV. Only 1% change in POsm will stimulate ADH release, whereas a drop of 10% of blood volume is necessary to stimulate ADH release.

Answer 241

a. Vasopressin binds to its receptors on the cells of the distal tubule and collecting duct (V2, cyclic AMP dependent receptors) b. When these receptors are activated => increases water permeability of the luminal membrane by the insertion of aquaporin-2 water channels in the apical membrane of the renal epithelial cells. c. This allows a more rapid passive flow of water from the lumen through the epithelial cells and into the solute-rich, concentrated interstitium => causing a rapid and marked increase in osmolality within the tubular lumen.

Answer 242

Complete or partial lack of secretion of vasopressin from the posterior lobe of the pituitary gland.

Answer 243

Brain surgery, trauma, immune-mediated diseases, neoplasia, infectious and hereditary disorders.

Answer 244

a. A syndrome that occurs in about 25% of long-term survivors from brain trauma and includes suppression of hormone release from the anterior pituitary gland but it can also include decreased vasopressin secretion from the posterior pituitary gland. b. Posttraumatic CDI is thought to resolve within a few days in most cases.

Answer 245

Trauma, neoplasia, idiopathic conditions and secondary to iatrogenic steroid administration or hyperadrenocorticism.

Answer 246

a. Often congenital. Few reports in young dogs, never in cats b. Miniature Poodle, GSD and Huskies c. No

Answer 247

a. Hypercalcemia b. Hypokalemia c. Pyelonephritis d. Pyometra and gram-negative sepsis e. PSS f. Liver insufficiency g. Hypoadrenocorticism (dogs) h. Hyperthyroidism (cats)

Answer 248

Interference with vasopressin binding and subsequent activation of the V2 receptors.

Answer 249

a. Due to abolition of the medullary hypertonicity gradient – medullary washout b. Medullary washout occurs in SA for 2 common reasons: i. Results from large amounts of urine passing through tubules – in severe PU/PD animals (Cushing’s or high IV fluid therapy) ii. The solutes necessary to produce the medullary hypertonicity gradient are lacking (insufficient urea in dogs and cats with hepatic insufficiency), low Na in Addison’s patients. iii. They will have secondary NDI and severely PU/PD despite normal renal function and normal vasopressin concentrations.

Answer 250

a. Rule out other common causes of PU/PD b. History, PE, hematology, biochemistry, UA and urine analysis

Answer 251

With normal or high normal urea and creatinine and a consistently isosthenuric urine.

Answer 252

When a dog drinks excessively for no apparent physiologic reason

Answer 253

We can have a misdiagnosis. Dogs with Cushing’s may appear to have CDI per results of these tests and therefore will be treated with desmopressin acetate instead of being correctly diagnosed as Cushing’s

Answer 254

Dogs with psychogenic polydipsia: will be slightly overhydrated, low osmolality and low serum sodium concentrations. Dogs with other causes of PU/PD including CDI: slightly dehydrated with relatively high serum sodium concentration and serum osmolality.

Answer 255

<280mOsm/L

Answer 256

a. Modified Water Deprivation Test b. Desmopressin Acetate Trial

Answer 257

On the premise that a dog that truly suffers from DI will not be able to concentrate its urine even under conditions of moderate dehydration due to a lack of ADH (CDI) or inappropriate renal response to ADH (NDI).

Answer 258

Once dehydration has been achieved w/o an appropriate rise in USG, desmopressin is given IM. A marked increase in USG would be diagnostic for CDI. A complete lack of response to desmopressin would be suggestive of NDI.

Answer 259

a. Medullary washout can occur – urine concentration will not happen despite endogenous ADH, desmopressin and intact renal V2 receptors b. Partial CDI or relative lack of vasopressin can be very hard to diagnose c. Dogs with Cushing’s may appear to have CDI – important to rule it out before doing any further testing

Answer 260

Acute, severe hypernatremia

Answer 261

a. Safer option than the MWDT b. Performed at home c. Collect urine first thing in the am for a few days and slightly limit access to water if possible. d. Begin therapy with desmopressin => on days 5, 6 and 7 collect first morning urine again. e. Bring all samples to the vet to measure USG. f. USG should improve dramatically after desmopressin (CDI). Complete lack of response (NDI or psychogenic polydipsia).

Answer 262

Intracranial mass lesions – recommended further imaging.

Answer 263

a. Desmopressin b. Thiazide diuretics, salt restricted diets. c. No treatment.

Answer 264

Schwartz-Bartter’s syndrome

Answer 265

a. CNS disorders b. Pulmonary lesions c. Malignancies d. Drugs e. Others (pain, nausea, psychologic stress)

Answer 266

a. Hypothalamic tumors b. Granulomatous ME c. Congenital hydrocephalus d. Distemper encephalitis

Answer 267

a. Bacterial pneumonia, aspergillosis, lung tumors, PPV, dirofilariasis b. Tumors that ectopically produce ADH or diseases that interrupt the inhibitory impulses in vagal afferents from stretch receptors in the atria and great veins. c. PPV – may inhibit low-pressure baroreceptors and stimulate release of ADH.

Answer 268

Antidepressants, neuroleptics (ACE, chlorpromazine), antineoplastics (cyclophosphamide), NSAIDs, opioids

Answer 269

Ones belonging to the underlying diseases + signs of hyponatremia (CNS)

Answer 270

a. Hyponatremia secondary to renal retention of free water and ongoing natriuresis b. Serum osmolality <280mOsm/L c. Urine osmolality >150mOsm/L d. Urine sodium usually >20mEq/L

Answer 271

Because of a continued natriuresis

Answer 272

Ruling out other causes of hyponatremia

Answer 273

a. Treat underlying disease b. DC fluids and restricted access to water c. Emergency treatment for hyponatremia

Answer 274

a. Hypertonic saline (3%) over 2-4h b. Not to increase Na levels more than 12mEq/L/day c. Initial goal of Na = 125-130mEq/L d. Furosemide may also be beneficial to inhibit resorption of water in the renal tubules and reduce the risk of volume overload. e. Possible complication: if hyponatremia is corrected too fast, central pontine myelinolysis

Answer 275

Demeclocycline – tetracycline antibiotic, potentially nephrotoxic. May take 1-2 weeks to work. Lithium – not used due to higher toxicity than demeclocycline

Answer 276

A multisystem disorder resulting from organ exposure to excessive amounts of thyroid hormone

Answer 277

a. Thyrotoxicosis: any condition in which there is an excessive amount of circulating thyroid hormone, whether from excess production and secretion from an overactive thyroid gland, because of leakage from a damaged thyroid gland or from an exogenous source. b. Hyperthyroidism: thyroid gland hyperfunction c. Yes, but is very rare

Answer 278

a. Older feline patients b. Rarely in dogs with thyroid carcinoma or extreme oversupplementation of thyroid replacement hormone to hypothyroid dogs.

Answer 279

a. High levels of circulating thyroid hormone – no difference between thyroid storm patients and stable hyperthyroid – difference is clinical signs b. Rapid, acute increases in circulating thyroid hormone – magnitude of change in serum thyroid hormone levels more important than the actual levels itself. c. Hyperactivity of the sympathetic nervous system – many clinical signs and physiologic signs are similar to those seen during catecholamine excess. Thyroid hormones can alter tissue sensitivity to catecholamines at the cell surface receptor as well as the intracellular signaling levels. d. Increased cellular response to thyroid hormones – is the case when thyroid storm results from infection, sepsis, hypoxemia, hypovolemia and lactic acidosis or ketoacidosis.

Answer 280

a. Radioactive iodine therapy b. Thyroidal or parathyroidal surgery c. Abrupt withdrawal of antithyroid medications d. Stress e. Non thyroidal illness f. Administration of iodinated contrast dyes g. Administration of stable iodine compounds h. Vigorous palpation of the thyroid

Answer 281

a. Fever b. CNS effects, from mild agitation to seizures or even coma c. GI and hepatic dysfunction ranging from vomiting, diarrhea and abdominal pain to unexplained jaundice d. Cardiovascular effects – sinus tachycardia, heart block, atrial fibrillation, Vtach, CHF

Answer 282

Hemorrhage, edema, degeneration or even retinal detachment, especially in hypertensive thyrotoxic cats.

Answer 283

As a result of thromboembolic disease secondary to the acute thyrotoxicosis

Answer 284

a. Identification of thyrotoxicosis – elevated total T4, or total T4 in the high-normal range combined with an elevated free T4 level. b. Clinical sings c. Evidence of a precipitating event

Answer 285

a. Mild erythrocytosis, macrocytosis and Heinz body formation b. Mature neutrophilia, lymphopenia and eosinopenia (stress response) c. Elevated liver enzyme levels d. Mild hyperglycemia e. Severe hypokalemia f. Unexplained mild hyperbilirubinemia g. Decreased Na/K ratio in cats that experience HF and pleural effusion

Answer 286

a. Reduce production and/or secretion of thyroid hormones b. Counteract the peripheral effects of thyroid hormones c. Systemic support d. Identify and remove precipitating factor

Answer 287

a. Prevents the synthesis of active thyroid hormone. First line of defense. b. It does not prevent the secretion of already formed thyroid hormones. c. If suspected renal insufficiency – reduce dosage.

Answer 288

a. Iodine compounds such as potassium iodide b. Lipid-soluble radiographic contrast agents – iopanoic acid – has the additional advantages of blocking peripheral conversion of T4 to T3, blocking T3 from binding to its receptors, and inhibiting thyroid hormone synthesis. c. Dexamethasone can be used to inhibit the release of thyroid hormone from the thyroid gland and to block the peripheral conversion of T4 to T3 (works synergistically with organic iodine compounds.

Answer 289

B-adrenergic receptor blockers like propranolol and atenolol.

Answer 290

Because it inhibits the peripheral conversion of T4 to T3

Answer 291

Esmolol, as CRI due to short half-life.

Answer 292

a. Peritoneal dialysis b. Plasmapheresis c. Hemodialysis d. Cholestyramine – binds thyroid hormone in the GI tract and inhibits enterohepatic circulation

Answer 293

a. Fluid therapy b. Dextrose supplementation and B vitamin supplementation c. Treat CHF – B blockers, furosemide, ACE inhibitors, nitroglycerin… d. Treat arrhythmias e. If thromboembolic disease – aspirin, UFH, LMWH f. If hypertension – amlodipine, B-blockers

Answer 294

Multifactorial i. Decreased blood flow and oxygen delivery to the brain ii. Hyponatremia iii. Lack of a direct effect of thyroid hormone on the brain iv. Disruption of the integrity of the blood-brain barrier

Answer 295

Multifactorial i. Inadequate thyroid hormone function in the hypothalamus – may result in inability to regulate body temperature ii. Decrease in the calorigenic effect of thyroid hormones contributes to hypothermia iii. Body temperature in some individuals with myxedema coma may be normal because of a concurrent infection and fever

Answer 296

Increase the number of B-adrenergic receptors and their affinity to catecholamines, thereby increasing the inotropic and chronotropic effects of catecholamines.

Answer 297

a. Bradycardia b. Decreased cardiac contractility c. Cardiac enlargement d. Hypotension – although diastolic hypertension has also been documented

Answer 298

a. It is a complication of hypothyroidism b. Develop secondary to accumulation of the glycosaminoglycan - hyaluronic acid in the dermis c. Impaired renal perfusion secondary to decreased cardiovascular function results in inability to excrete water and contributes to development of edema. d. Excessive secretion of ADH may also contribute to hyponatremia, fluid retention and edema in some patients.

Answer 299

a. Rottweiler – most dogs are middle age, no gender preference b. Dogs with untreated hypothyroidism c. Concurrent disorder, most commonly an infection (aspiration pneumonia, FB, keratoconjunctivitis, pyometra, pyoderma, severe bilateral otitis, UTI, sepsis). d. Glucocorticoids – lower the concentration of thyroid hormones in dogs e. NSAIDs – may cause suppression of thyroid stimulating hormone (TSH) secretion f. Surgery g. Other: burns, CO2 retention, GI hemorrhage, hypoglycemia, infection, hypothermia, stroke, trauma, various medications (anesthetics, barbiturates, B-blockers, diuretics, narcotics, phenothiazines and tranquilizers)

Answer 300

a. Overweight/obese b. Nonpitting facial, jaw or other edema c. Tachypnea, alopecia d. Dehydration e. Dermatitis f. Otitis g. Elevated or decreased body temperature h. Heart murmur i. Bradycardia/Tachycardia j. Neurological signs – mental dullness, stupor

Answer 301

a. Mild nonregenerative anemia – thyroid hormones bind thyroid hormone receptors on erythroid progenitors and act directly to increase erythroid proliferation and also they increase expression of the erythropoieting gene, contributing to RBC formation b. Hyperlipidemia – alteration in both synthesis and transport of lipids c. Hypercholesterolemia d. Hyponatremia – increased renal reabsorption of Na, impaired water clearance, increased ASH concentration, low plasma renin activity and a low aldosterone concentration e. Hypoglycemia – in humans secondary to reduced insulin clearance. In dogs – decreased insulin sensitivity which may lead to hyperglycemia f. Hypoxia and hypercarbia

Answer 302

Based on low thyroxine and high TSH concentrations – some dogs will have normal TSH

Answer 303

Glucocorticoids, NSAIDs, TMS, anticonvulsants (phenobarbital, KBr), antituberculosis drugs, propranolol and lithium

Answer 304

a. Increased hydrostatic pressure b. Decreased oncotic pressure c. Lymphatic obstruction d. Na+ retention e. Vascular endothelial leak syndromes

Answer 305

a. Supportive care b. Thyroid hormone supplementation c. Treatment of concurrent diseases

Answer 306

IV levothyroxine – 5mcg/kg q12h – higher bioavailability than oral – more rapid clinical response.

Answer 307

24 to 30h after administering the IV levothyroxine

Answer 308

Severely septic patients with altered HPA axis function may have a form of adrenal insufficiency.

Answer 309

Septic patients with either unexpectedly low basal plasma cortisol concentrations or those whose response to exogenous ACTH (termed “delta cortisol”: serum cortisol concentration 1 hour after exogenous ACTH administration minus base- line serum cortisol concentration) was deemed inadequate regardless of basal cortisol concentration.

Answer 310

It was a multicenter, international, randomized, double-blinded, placebo-controlled trial that set out to investigate the usefulness of the standard ACTH stimulation test and hydrocortisone treatment in 800 people with septic shock. The investigation ultimately included only 499 people because of slow recruitment and subsequent expiration of study medications.

Answer 311

1) That low-dose hydrocortisone treatment led to more rapid pressor weaning regardless of ACTH stimulation test results. 2) That hydrocortisone had no survival benefit despite more rapid pressor weaning in the treatment group. 3) That hydrocortisone treatment was associated with more incidents of superinfection than placebo.

Answer 312

In health, at least 90% of plasma cortisol circulates bound to corticosteroid-binding globulin (CBG). Unbound or “free” plasma cortisol is the biologically active fraction.

Answer 313

It has the capability to convert inactive cortisone to active cortisol, and under some conditions, to convert active cortisol to inactive cortisone.

Answer 314

1) The hypothalamus, pituitary, or adrenal glands may be inhibited or damaged by cytokines, reactive oxygen species, hemorrhage, or other deleterious events during septic shock -> inadequate cortisol production or inadequate response to administered ACTH. 2) Plasma CBG is damaged by neutrophil elastase -> during systemic inflammatory states, an increased fraction of total plasma cortisol is in its active form. 3) Standard tests for cortisol concentration measure only total plasma cortisol -> true cortisol activity potential may be underestimated in patients with sepsis. 4) The 11B-HSD1 enzyme system is stimulated by proinflammatory cytokines and by high concentrations of glucocorticoids -> increases in active intracellular cortisol that are not reflected by measurement of plasma cortisol concentration. 4) Systemic inflammation inhibits GR-cortisol binding, impairs translocation of the complex to the nucleus, and alters cortisol-dependent gene transcription. The variety of ways in which systemic inflammation can potentially affect the secretion and biological activity of cortisol makes the precise mechanisms of CIRCI difficult to know.

Answer 315

Is currently made by evaluating response to treatment with low-dose hydrocortisone, because current guidelines recommend treating pressor-resistant septic shock patients with hydrocortisone without or with no regard to HPA axis assessment.

Answer 316

1) One investigation found that septic dogs with a delta cortisol <3ug/dL following a standard 250ug/dog ACTH stimulation test were more likely to be hypotensive and had decreased survival compared to dogs with a cortisol increase >3ug/dL. This difference would suggest that dogs with cortisol increase <3ug/dL may have CIRCI. 2) A study in septic and nonseptic critically ill dogs found that patients with a delta cortisol <3ug/dL 1 hour after 5ug/kg cosyntropin administration were more likely to be pressor-dependent than dogs with delta cortisol >3ug/dL. Findings from these 2 studies suggest that ACTH responsiveness may be a marker of illness severity in critically ill dogs and raises the question of whether they may benefit from glucocorticoid replacement.

Answer 317

They that critically ill cats had higher baseline cortisol concentrations than normal cats, as would be expected in response to physiologic stress. However, there was no significant difference between baseline cortisol, post-ACTH stimulation cortisol, or delta cortisol concentrations in cats that died and those that survived. Cats with neoplastic disease were found to have lower delta cortisols compared to other critically ill cats in the study.

Answer 318

Costello et al studied 19 septic cats and reported significantly lower delta cortisols in septic cats compared to normals. However, there was no difference in delta cortisol between survivors and nonsurvivors in this investigation.

Answer 319

Hydrocortisone has approximately 1/4 the potency of prednisone

Answer 320

Hydrocortisone dose should not exceed 300 mg per adult person (#70 kg) per day for treatment of CIRCI. The dose is referred to as low or physiologic, and calculates to no more than 4.3 mg/kg/day of hydrocortisone. As hydrocortisone has approximately 1/4 the potency of prednisone, the daily dose should not exceed 1 mg/kg of prednisone equivalent.

Answer 321

Because its profound HPA axis suppression may complicate accurate ACTH stimulation testing. Since it is currently not recommended to use the ACTH stimulation test to guide CIRCI treatment decisions, dexamethasone may be a reasonable treatment choice; However, dexamethasone is highly structurally altered from the parent cortisol molecule and may therefore carry excessive immunosuppressive effects without the benefit of hydrocortisone’s modest mineralocorticoid effect.

Answer 322

* 1–4.3 mg/kg hydrocortisone daily, either divided into 4 equal IV doses administered every 6 hours or delivered as a constant rate infusion * 0.5 mg/kg hydrocortisone IV every 6 hours or 0.08 mg/kg/hr as a constant rate infusion.

Answer 323

Regulates cell function by binding to cell membrane calcium-sensing receptors

Answer 324

Messenger to transport cell surface signals to interior

Answer 325

mg/dL x 0.2495 = mmol/L

Answer 326

99% of the total body calcium

Answer 327

Enhance calcium absorption in the GI tract. Will also increase phosphorus uptake.

Answer 328

1,25 dihydroxycholecalciferol

Answer 329

When they decrease they will stimulate the production of PTH. When they increase they will decrease the production of PTH.

Answer 330

Transient receptor potential vanilloid type 6 (TRPV6)

Answer 331

The calbinding

Answer 332

Through 2 receptors: - Na exchanger (NCX1) - Mg exchanger (PMCA16) -> if hypomagnesemia, that will lead to difficulties raising calcium if it is also low -> check Mg and supplement PRN when having refractory hypocalcemia.

Answer 333

The renal hydroxylation of vitamin D, catalized by 1-alpha-hydroxylase in the proximal renal tubule.

Answer 334

AKA - renal osteodystrophy CKD associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism

Answer 335

Is a phosphatonin released from osteocytes in response to increased phosphorus, calcitriol, and PTH concentrations. Increased FGF-23 is an independent risk factor for progression and survival of CKD in humans, dogs, and cats.

Answer 336

FGF-23 binds to coreceptor α-klotho -> decreases phosphorus and calcitriol concentrations - Downregulating sodium-phosphorus cotransporters (NaPi-IIa and IIc) in renal proximal tubules -> phosphaturia - Inhibiting renal 1α-hydroxylase activity -> no vit D Fibroblast growth factor-23 decreases PTH secretion in the early stages of CKD In advanced stages, FGF-23 leads to decreased calcitriol, indirectly promoting development of hyperparathyroidism (calcitriol is needed for PTH gene transcription).

Answer 337

There will be increases in postprandial phosphorus that will bind to calcium, forming the CPP (calciprotein particles), actively participating in inflammation and damage to the kidneys.

Answer 338

Secondary hyperparathyroidism occurs when the parathyroid glands become enlarged and release too much PTH, causing a high blood level of PTH, normally secondary to kidney disease. Phosphorus retention Kidneys cannot make active vitamin D -> needed to absorb calcium -> lower blood calcium levels -> increased PTH production.

Answer 339

10 minutes

Answer 340

When due to different conditions (for example ethylene glycol intoxication), calcium binds to other than proteins (citrate, lactate, bicarbonate, phosphate), and can decrease the ionized calcium. Normally the fraction of ca2+ complexed is low.

Answer 341

Muscle tremors / fasciculations Seizures Tetany Status epilepticus Facial rubbing Paw chewing Behavior changes

Answer 342

Hypoalbuminemia (ionized usually normal) CKD (ionized usually normal) Puerperal tetany ("eclampsia") Acute renal failure Acute pancreatitis Idiopathic (usually mild, not clinical)

Answer 343

Because when extracellular fluid calcium decreases, the nervous system becomes more excitable due to increased neuronal membrane permeability, and nerve fibers discharge spontaneously.

Answer 344

iCa < 0.8mmol/L or clinical signs. Treat to control clinical signs, not to normalize values Most likely Ph is increased -> if we increase the Ca, we can make the renal disease worse.

Answer 345

When you have severe malabsorption disease patients become vitamin D deficient

Answer 346

About 25mg/mL