Endocrine Flashcards
What cells are pheochromocytoma derived from?
Chromaffin cells of the adrenal medulla.
Chromaffin cells also called APUD cells → responsible for amine precursor uptake and decarboxylation
What are the clinical signs of pheochromocytoma?
- Systemic hypertension
- Tachyarrhythmias/ bradyarrhythmias
- syncope
- v/d
- PUPD
- tachypnea
- abdominal distention/pain
True or False: High concentration of urinary normetanephrine was highly suggestive of pheochromocytoma.
True
* Urinary normetanephrine-to- creatinine ratio proved to be superior to epinephrine-, norepinephrine-, or metanephrine-to-creatinine ratios
In human, what drug can be given to reverse the catecholamine-induced vasoconstriction from pheochromocytoma?
Phentolamine, an reversible non-selective α-adrenergic antagonist
What drugs should be avoided in pheochromocytoma patients due to possible acute hypertensive crisis?
- Metoclopramide: In patients with pheochromocytoma, metoclopramide can cause a surge in catecholamine release from the tumor by antagonizing presynaptic dopaminergic inhibition. Normally, dopamine acts to inhibit norepinephrine release, so blocking this effect leads to increased norepinephrine release.
- Histamine: can case vasodilation with reflex tachycardia and further vasoconstriction
- Glucagon: activates adenylate cyclase, leading to an increase in intracellular cyclic AMP (cAMP), which can promote catecholamine secretion from the tumor
What are the pre-, peri-, and post- anesthetic management for pheochromocytoma?
Pre:
1) start non-competitive α-adrenergic blockade with phenoxybenzamine (0.5 to 2.5 mg/kg PO q12h) 1 week before sx
2) blood type
Peri:
1) opioid + bzd + propofol for premed and induction
2) avoid halothane → sensitizes the myocardium to catecholamine- induced arrhythmias
3) monitor ECG and blood pressure
4) prepare esmolol (0.05 to 0.5 mg/kg IV followed by 10 to 200 mcg/kg/min IV), vasodilators such as nitroprusside (0.5 to 5 mcg/kg/min IV) or magnesium sulfate
5) prepare phenylephrine (0.5 to 5 mcg/kg/min IV) or norepinephrine (0.1 to 2 mcg/kg/ min IV) because patient may become hypotensive after tumor removal
What is the medical management for pheochromocytoma?
Phenoxybenzamine, β-blockers, and/or other anti-arrhythmic agents
* β-Blockers should not be given without concurrent α-blockade → loss of β2 receptor–mediated vasodilation may exacerbate hypertension
What is Budd-Chiari-like syndrome?
Mechanical obstruction of the hepatic venous outflow → liver congestion, right upper quadrant pain, ascites
For pheochromocytoma, what are the negative prognostic indicators for surgical outcome?
- Vena cava invasion
- older age
- intra-op arrhythmias
- prolonged surgical time
How are NE and Epi synthesized?
Tyrosine enters the nerve → DOPA → Dopamine → enters the vesicles → NE → exits the vesicle and receives a methyl group → Epi → re-enters the vesicles
Resources: https://cvpharmacology.com/norepinephrine
How are NE and Epi metabolized?
1) Neuronal re-uptake
2) Catechol-o-methyltransferase (COMT) and monoamine oxidase(MAO)
How is the ketone body synthesized?
Fatty acids went through 𝜷-oxidation and form Acetyl-CoA.
Normal situation: Glucose degraded into pyruvate → both Acetyl-CoA and pyruvate enter TCA cycles
Diabetic: No pyruvate; two Acetyl-CoA → form ketone bodies
What are three types of ketone bodies?
Acetoacetate (strong acid)
𝜷-hydroxybutyrate (strong acid)
acetone
Which ketone body cannot be detected by the urine strip test (nitroprusside reaction)?
𝜷-hydroxybutyrate
Why occasionally there will be negative urine ketone on day 1 but became positive on day 2 or 3 after the treatment is started?
After starting the insulin treatment, the urine 𝜷-hydroxybutyrate : Acetoacetate ratio may decrease because more 𝜷-hydroxybutyrate is metabolized back to acetoacetate and therefore can be detected with nitroprusside test
What are the most common concurrent diseases in dogs with DKA?
Acute pancreatitis
Bacterial UTI
Hyperadrenocorticism
What are the most common concurrent diseases in cats with DKA?
Hepatic lipidosis
CKD
Acute pancreatitis
Bacterial/viral infection
Neoplasia
What is the concentrations of K and Phos in Kphos?
K: 4.4 mEq/ml
Phos: 3 mM/ml
What is the rate to supply phos in patient with DKA and hypophoshpatemia?
0.03 - 0.12 mM/kg/hr
Describe the CRI regular insulin protocol for DKA.
What is the recommendation from The American Diabetes Association for bicarb supplementation for pediatric DKA patients?
1) Who should be treated?
who maintain a pH < 7.0 after 1 hour of fluid therapy
2) How to treat it?
Sodium bicarb 2 mEq/kg added to 0.9% NaCl, in a solution that does not exceed 155 mEq/L of sodium over 1 hour.
3) How to monitor?
The pH is monitored q1h and treatment is repeated until pH ≥ 7.0
What is the hallmarks for HHS?
- BG > 34mmol/L (600 mg/dL)
- Minimal or negative urine ketone
- Serum osmolarity > 350 mOsm/kg (cat) or 325 mOsm/kg (dog)
- Ketotic vs non-ketotic
Describe the pathogenesis of HHS.
1) Hormone alteration
Insulin deficiency + increased countercurrent hormone (e.g. epinephrine, glucagon, cortisol, growth hormone)
- Epinephrine & glucagon inhibit insulin-mediated glucose uptake in muscle and stimulate hepatic glycogenolysis and gluconeogenesis
- Cortisol & growth hormone inhibit insulin activity and potentiate the effects of glucagon and epinephrine
2) severe osmotic diuresis due to hyperglycaemia (usually extreme)
3) dehydration and decrease GFR
4) worsening of hyperglycaemia
such extreme hyperglycaemia can only occur with decreased GFR as once reached threshold the rest of glucose should be excreted with urine
What is the main difference between HHS and DKA?
HHS usually has higher BG level and higher osmolarity. Patients with HHS also have higher circulating insulin level and lower glucagon level → this inhibits the liver to perform lipolysis due to presence of insulin.
What is the equation of serum osmolality?
Serum osmolality (mOsm) = 2 x Na + BUN/2.8 + BG/18
- Unit for Na = mEq/L
- Unit for BUN & BG = mg/dL
What is the equation of effective osmolality
Effective osmolality (mOsm) = 2 x Na + BG/18
What are the main contributors for metabolic acidosis in DKA and HHS, respectively?
DKA: ketones
HHS: uremic acids, lactic acids
What is the equation to correct Na in HHS patient?
Corrected Na = Patient’s Na + 1.6 x [(Measured BG - Normal BG)/100]
- Unit for Na = mEq/L
- Unit for BG = mg/dL
True of False: For HHS management, using IM or IV protocols of regular insulin at dosages 50% of those used for DKA should reduce the risk of a too rapid decline of serum glucose.
True
What is the target rate to reduce BG in HHS patients?
No more than 2-4 mmol/L/hr
True or False: Many dogs with HHS has recent steroid administration
True (18%)
- In the same study, poor outcome was associated with abnormal mentation and low venous pH
Reference: Trotman TK, Drobatz KJ, Hess RS. Retrospective evaluation of hyperosmolar hyperglycemia in 66 dogs (1993-2008). J Vet Emerg Crit Care (San Antonio). 2013;23(5):557-564.
How is potassium affected in patients with DKA/HHS?
1) Acidosis → K+ is shifted out of the cell in exchange with H+
2) Decreased dietary intake → K ↓
3) Hypovolemia induced hyperaldosteronism → increased renal loss
4) Insulin deficiency → decreases the amount of K co-transported into cells
5) Decreased GFR → K accumulates in the blood
True or False: The BG level in the brain is the same as plasma.
False
Glucose concentrations in the brain are up to 30% lower compared to plasma
The brain relies on facilitated diffusion via GLUT-1 and GLUT-3 (insulin independent)
What is the cutoff to diagnose insulinoma with insulin:glucose ratio?
Amended Insulin-Glucose Ratio (AIGR) > 30 is supportive of insulinoma
- Equation: AIGR = (insulin × 100) ÷ (plasma glucose − 30)
- Need to collect the blood when BG < 60
Where is the glucagon from? Where does it work?
1) 𝜶 cells in the pancreas
2) liver, promote glycogenolysis and gluconeogenesis
When should you raise a concern for insulin resistance?
when insulin dose > 1.5U/kg q12h
What are the four factors contributing to thyroid storm in cats?
1) Higher concentration of circulating thyroid hormone
2) Acute, rapid increase of circulating thyroid hormone
3) Hyperactivity of the sympathetic nerve system
4) Increased cellular response to thyroid hormone
What is the axis stimulating thyroid synthesis?
TRH from hypothalamus → TSH from Anterior pituitary gland → thyroid gland
What are the differences between T3 and T4?
T4 (thyroxine)
- 93% of the thyroid hormone released from the gland
- When enters the cells, one iodide is removed and most of T4 are converted to T3
T3 (triiodothyronine)
- 7% of the thyroid hormone released from the gland
- biologically active form
- Has much higher affinity to the intracellular receptors for nucleus transcription
List 5 precipitating events for feline thyroid storm.
Stress
Vigorous palpation of the thyroid
Thyroidal or parathyroidal surgery
Radioactive iodine therapy
Sudden withdrawal of the methimazole
Administration of iodinated contrast dyes
Administration of stable iodine compounds
Nonthyroidal illness (e.g. infection)
Amiodarone therapy
Is T4 and T3 highly protein bound? What are the protein they bind to?
Yes both are highly protein-bound
About 60% is bound to thyroxine binding globulin, 17% to transthyretin, 12% to albumin and 11% to various lipoprotein fractions.
Only about 0.3 - 1% are free form (active form)
What is the MOA for methimazole?
Methimazole inhibits the action of thyroid peroxidase → inhibits the incorporation of iodide into thyroglobulin → decrease T4 & T3 production
Dose: 5mg per cat q12h
What are the medical treatments to decrease thyroid hormone production/secretion for suspect thyroid storm?
1) **methimazole **(cannot stop the release of stored thyroid hormone)
2) potassium iodide (stable iodine compounds)
- Prevent secretion of thyroid hormone
- Need to give 1 hr after methimazole administration
- 25mg PO q8h
3) **iopanoic acid **(lipid-soluble radiographic contrast agent)
- Prevent secretion of thyroid hormone
- block peripheral conversion of T4 to T3
- block T3 from binding to its receptor
- inhibit thyroid hormone synthesis
- 100mg per cat PO q12h
4) Dexamethasone
- inhibit peripheral conversion of T4 into T3
- 0.1-0.2 mg/kg PO/IV
Why illness can cause decreased thyroid hormone production?
Illness can increase plasma glucocorticoid concentration → inhibit TSH secretion from anterior pituitary gland
What are the pros and cons for each beta blockers for treating feline thyroid storm?
Propranolol
- Pros: can inhibit peripheral T4 conversion to T3 (slow)
- Cons: poor oral bioavailability, short half-life (need TID)
- 5mg PO q8h
Atenolol
- Pros: better oral bioavailability and SID administration
- Cons: doesn’t affect the T4 conversion
- 1 mg/kg PO q12h-q24h
Esmolol
- very short acting
- 0.1-0.5 mg/kg IV, followed with CRI 10-200 mcg/kg/min
However remember that propanolol not a selective 𝛽 blocker, so can be detrimental in asthamtic cats and also can cause hyperglycaemia.
What are the clinical signs in cats with feline thyroid storm (organ system)?
Fever
GI system
CNS
Cardiovascular system
Hypercoagulable state
Which breed is predisposed to hypothyroid crisis?
Rottweiler
What are the 6 classic hallmark for hypothyroid crisis?
myxedema (accumulation of glycosaminoglycan hyaluronic acid) in the dermis
coma
hypothermia
bradycardia
hypoventilation
hypotension
What are the risk factors of developing hypothyroid crisis?
Infection (e.g. pneumonia)
NSAIDs or glucocorticoid use
Surgery
Others in humans: burns, hypoglycemia, infection, hypothermia, trauma, and various medications, including anesthetics, barbiturates, narcotics, phenothiazines, and tranquilizers.
What are the six hormones that the anterior pituitary gland produces?
What are the two hormones that the posterior pituitary gland produces?
Anterior glands
ACTH (Adrenocorticotrophic hormone)
TSH (Thyroid-stimulating hormone)
Growth hormone (GH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin
Posterior glands
Oxytocin
Vasopressin
* These hormones are synthesized in the hypothalamus and stored in the posterior pituitary gland
List the 4 stimulating hormones and 2 inhibitory hormones released by the hypothalamus.
Describe the anatomic compositions of adrenal glands and the hormones each part secretes
From outside to inside:
Cortex
- Glomerulosa: Aldosterone (minerocorticoid)
- Fasciculata: Glucocorticoid
- Reticularis: sex hormones
Medulla: catecholamine
What are the protein-binding and half life of minerocorticoid and cortisol, respectively?
Cortisol: highly protein bound (~ 90%), 60-90 min
Minerocorticoid: 60% protein bound, 20 min
True or False: Besides glucocorticoid, ACTH can also stimulate minerocorticoid release.
True (to a lesser extent)
What is the original source of all the adrenal hormone?
Cholesterol
In the synthesis of adrenal hormones, which step is the rate limiting step?
Conversion of cholesterol to pregnenolone
Describe the function of aldosterone
- Mainly works at the collecting duct
- Account for 5-10% Na absorption
- At the principle cells
- Increases number of epithelial Na channels (ENaC) and Na-K ATPase → increase Na and water resorption and K excretion
- At the intercalated cells
- Increases H ion pump → increases H secretion in exchange with Na
- At the colon
- Increases Na resorption (small amount)
According to a multicenter study published by Hauck and colleagues in 2020, what is the prevalence of hypoadrenocorticism in dogs with chronic GI signs?
4% (6/151)
Reference: Hauck C, Schmitz SS, Burgener IA, et al. Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: A multicenter study. J Vet Intern Med. 2020;34(4):1399-1405.
Name 5 drugs that can cause iatrogenic hypoadrenocorticism.
Trilostane
Ketoconazole
Mitotane
Phenobarbital
Etomidate
What is the characteristics of stress leukogram
Neutrophilia
Lymphopenia
Eosinopenia
+/- Monocytosis
List 5 pseudo-Addison’s diseases.
Severe GI diseases
Heavy GI parasites (whipworms)
Kidney diseases
Pregnancy
Body cavity effusion
CHF
What is the full name for DOCP and the starting dose?
Deoxycorticosterone pivalate
2.2 mg/kg SC or IM
Why do dogs with Addison’s disease hypoglycemic?
Cortisol facilitates glycogenolysis and gluconeogenesis → lack of cortisol may lead to decrease glucose production
Why patients with Addison’s disease can have low USG despite severely dehydration?
medullary washout secondary to hyponatremia
What are the possible complications from sodium bicarb administration?
1) Hypokalemia
2) Hemolysis from hyperosmolality
3) Paradoxical intracellular acidosis
4) Hypernatremia
5) Decreased ionized calcium level → decreased ventricular contractiliy
Increase pH → increased binding of Ca to albumin
6) Shifting the oxygen-hemoglobin association curve to the left (Bohr effect) → increases binding → decrease O2 delivery
7) Hypervolemia
True or False: Dexamethasone has both minerocorticoid and glucocorticoid effect
False
Dexamethasone only has glucocorticoid effect
Write down the different steroid, their minerocorticoid and glucocorticoid effects, plasma half life, and biological half-life.
What are the differences in results between French study and CORTICUS study?
1) French study (n=300): for non-responders to cortioctropin test, those received hydrocortisone (50mg IV q6h for 7 days) and fludrocortisone (50mg PO SID) had lower mortality rate and higher percentage of pressor withdrawal rate
2) CORTICUS study (n=499): patients (both responders and non-responders) received hydrocortisone (50mg IV q6h for 6 days) doesn’t have different mortality rate than the placebo group. In the hydrocortisone group, shock was reversed more rapidly but patients had more episodes of superinfection or new sepsis.
True or False: The 2013 Surviving Sepsis Campaign recommends patients with suspected CIRCI should be confirmed with ACTH stimulation test before starting the treatment.
False
The 2013 Surviving Sepsis Campaign guidelines suggest NOT using ACTH stimulation testing to identify which patients should be treated with hydrocortisone.
What are the proposed pathophysiology of CIRCI?
1) inflammation, infarct, hemorrhage or iatrogenic cause of adrenal gland insufficiency
2) systemic inflammation leads to decreased corticosteroid-binding globulin (CBG) production
3) cytokines lead to dysregulated intracellular glucocorticoid receptors (e.g. inhibits binding & gene transcription) & enzymes
What are the common PE and clinical pathological findings for primary hyperaldosteronism?
Systemic hypertension, hypokalemia
*patients usually don’t have hypernatremia due to concurrent water retention and dilution (total body sodium does increase)
Fill out the blank
How many parathyroid glands do dogs and cats have?
4 glands (two on each side)
What can stimulate PTH production? What can inhibit PTH production?
Stimulation:
low ionized Ca level, high phos level, acidosis, catecholamines, prostaglandin E2
Inhibition:
high ionized Ca level, calcitriol, FGF-23, very high Mg
What can stimulate calcitriol production? What can inhibit calcitriol production?
Stimulation:
low ionized Ca level, low phosphorus level, PTH, low Ca diet, estrogen, testosterone
Inhibition:
high ionized Ca level, high phosphorus level, FGF-23, calcitriol
Describe the calcium distribution.
99% in the bone as hydroxyapatite
For the remaining 1%
about 55% as ionized calcium, 35% protein-bound and the remaining 10% complexed with other electrolytes (e.g. phosphate, bicarb, magnesium, citrate, lactate)
Describe the phosphorus distribution.
85% in the bone as hydroxyapatite, 15% in soft tissue (e.g. muscles), less than 1% in the ECF
For those in ECF:
2/3 are organic form (e.g. phospholipid)
1/3 are inorganic form (what we measured)
85% H2PO4- and HPO42-
10% Protein-bound
5% Complexed with calcium and magnesium
True or False: PTH only secretes when the ionized calcium is low.
False
PTH is constantly secreted from the parathyroid gland. It has very short half-life (3-5 min).
How much percentage drop of iCa can elicit max PTH secretion?
10%
True or False: PTHrP functions as calcium-regulating hormone in fetus and is produced from placenta.
True
What are the three endocrines secreted from the pancreas?
Insulin - facilitate glucose uptake by the cells, glycogen synthesis, lipid and protein storage
Glucagon - glycogenolysis, gluconeogenesis
Somatostatin - inhibits the secretion of other pancreatic hormones such as insulin and glucagon
What do you need to monitor and supply in dogs with post-op parathyroidectomy?
Monitor total Ca and iCa twice daily
If patient shows clinical signs of hypocalcemia (e.g. tetany) - supply 10% Calcium gluconate 0.5-1 ml/kg slow IV over 15 minutes
Start calcitriol supplementation 0.02-0.03 ng/kg/d (divided into BID) for 2-4 days, and then taper to 0.005 - 0.015 ng/kg/d (divided into BID)
Slowly prolong the duration and recheck biweekly
May take 3-6 months to withdrawal
Describe aldosterone paradox
Aldosterone usually increases in response to hypovolemia and hyperkalemia. In patients with hypovolemia, aldosterone will facilitate Na and water retention, but the K+ secretion remains unchanged. In patients with hyperkalemia, aldosterone will facilitates K+ secretion but does not affect the Na+ resorption rate. It is proposed that the main difference lies in the presence of angiotensin II.
RAAS will be activated during the state of hypovolemia but not for hyperkalemia.
What are the 2 most common locations for intestinal intussuseption?
Enterocolic (ileocecocolic)
enteroenteric (jejunum)
How much of the small intestine can be removed in dogs and cats without developing short bowel syndrome?
50%
Which hormone increases the prolactin production and which hormone inhibit it?
Increase: estrogen
Decrease: dopamine
What are the 4 types of vasopressin receptors and what are their functions?
V1- vascular smooth muscle
V2 - renal collecting duct, platelet, endothelium, vascular endothelium
V3- pituitary gland
Oxytocin - uterus, GI tract, mammary gland
- Platelet also has V1R → facilitates thrombosis by increasing in intracellular Ca
- V3R also is responsible for all the CNS effect (e.g. temperature regulation, sleep)
List 5 things that can cause vasopressin release besides increased plasma osmolality and a decrease in circulating blood volume.
1) Pain
2) Nausea
3) Hypoxemia
4) Hypercapnea
5) Pharyngeal stimuli
6) Mechanical ventilation
7) Glycopenia
8) Angiotensin II
9) High dose opioid
10) Acetylcholine
11) Histamine
12) Glutamine
13) Prostaglandins
14) dopamine
How does glucocorticoid affect vasopressin?
It inhibits vasopressin release.
Interferes with cAMP formation
How does the body detect change in osmolality and induce vasopressin release? Where are the osmoreceptors?
Central receptor: in the third ventricle
Peripheral receptor: in the mesenteric and portal veins
What are the two pathways of vasopressin causing vasoconstriction?
1) Gq protein-coupled receptors → activate the phospholipase C and phosphoinositide pathways → activate voltage-gated calcium channels
2) Inactivation of K-ATP channels in the vascular smooth muscle cells → facilitate depolarization → opening of Ca channels
What type of receptor is V2 receptors?
Gs protein-coupled receptors
(→ increases intracellular cAMP → aquaporin-2 pop up at the luminal side)
Which V receptor does DDAVP bind to?
V2R
- So DDAVP can also cause vasodilation at afferent arterioles
How is vasopressin metabolized? What is it protein-binding?
NO protein-binding
Renal excretion (65%) and metabolism by tissue peptidases (35%)
What is the MOA of hyperadrenocorticism-induced hypertension?
Glucocorticoids induce hepatic production of angiotensinogen → exaggerated response of the renin-angiotensin system
What is Budd-Chiari-like syndrome?
Mechanical obstruction of the hepatic venous outflow → liver congestion, right upper quadrant pain, ascites
Which hypothalamic nucleus is responsibel for the synthesis of ADH?
SON (Supraoptic nucleus)
List the hormones synthetized by the PVN (Paraventricular Nucleus)
- Oxytocin (posterior hypophysis)
- CRH
- TRH
Apart from the SON and PVN which other nuclei are involved in the production of releasing hormones for the anterior hypophysis
Arcuate nucleus
* GHRH
* Dopamine (or PIH)
Pre-optic nucleus
* GRH
Oxytocin receptors on smooth muscles are ____ coupled
Gq
The target organ of GH is ____ and it acts via ____ coupled receptors
liver/hepatocytes
Tyrosine Kinase –> JAK activation –> STATs phosphorylation –> gene transcription of new proteins like IGF-1
* gluconeogenesis
* lypogenesis
IGF-1 on muscle = hypertrophy due to increased AA uptake + bone growth
TRH stimulates prolactin release
True: TRH inhibits secretion of PIH from arcuate nucleus so prolactin can be released from the anterior pituitary
T3 and T4 need receptors to enter the target cell
False: they are both highly lipid soluble
T4 is converted into T3 by ____ inside the target cell
5’ deiodinase
Cellular effects of T3
T3 acts as a transcription factor - increases Na/K ATPase synthesis
Relevance of KLOTHO protein
KLOTHO is an essential co-receptor for FGF-23
Absence of KLOTHO = hyperphosphatemia
What is the ratio of production of norepi:epi in adrenal glands?
20% norepi
80% epi
In beta pancreatic cells what is the intracellular mechanism triggering release of insulin
Glucose enters the beta cell via GLUT-2 (insulin independent). Increased intracellular glucose triggers the closure of K channels –> positive intracellular environment with opening of the Ca++ channel –> release of vescicles with insulin
Insulin receptors are ____ coupled
Tyrosin Kinase
How does glucose enter the alpha cells in the pancreas
via GLUT-1 which is insulin independent
Glucagone receptors are ____ coupled
Gs
Remember glucagone is inotrope and can be used in beta blocker toxicosis as it activates cAMP via an alternative route
What % of DKA patients have previously been receiving insulin?
40-50%
What’s the current evidence for timing of insulin administration in DKA
Although glycemic control is not a first priority in DKA treatment, there is no evidence of harm in starting insulin CRI within the first 6h of presentation (more rapid resolution of DKA actually)
What issues can arise with administering blood products to diabetic patients?
Anticoagulant is: citrate phosphate DEXTROSE adenine
possible that insulin requirements might increase
Where is beta hydroxybutirate produced?
Mitochondria of perivenous hepatocytes
Fatty acids from counter-regulatory hormones to hepatocytes
is B
How is acetone produced?
via decarboxylation (not in the mitochondria) from acteoacetate (irreversible)
Doesn’t contribute to acidosis as volitile (DKA odour) and not dissociating at physiologic pH
Why can’t AcetylCoA enter Kreb cycle during DKA?
It needs oxaloacetate which can’t be produced when low glucose
AcetylCoA shifted to oxydation and ketone bodies formation
What is the limiting rate step in ketolysis? why is it important?
To re-convert ketone bodies to AcetylCoA need enzyme SCOT which is mainly synthetised in heart, brain, kidney and skeletal muscle
Normal values for 2betaHB on ketometer
0-0.32mmol/L
DKA >3.8 (dogs) and >2.4 (cats)
Hypoglycaemia and the brain
Glucose-sensing neurons in hypothalamus. If low activates SNS. If not successful in normalizing BG then brain shifts to lactate use for energy and uses limited glycogen stores in astrocytes.
Exaustion of ATP occurs quickly with failure of Na/K pumps –> cell swelling, release of glutamate –> Ca++ toxicity –> mitochondrial damage and neuronal death
Whipple’s triad
- low BG
- clinical signs
- resolution of clinical signs with glucose supplementation
Emergency treatment of insulinoma
- glucagone 50ug/kg bolus and CRI 5-40ug/kg/min
- corticosteroids (if glucagone not available)
Mechanism of action of diazoxide
keeps Katp open –> no depolarization beta cell –> no insulin release
𝛿 cells
𝓔 cells
somatostatin (regulation of both insulin and glucagon secretion)
ghrelin (appetite regulation)
Amplification of insulin relase via alternative pathways of glucose metabolism
- incretins (GLP and GIP) release from enteroendocrine cells in the gut exposed to FFA stimulate B cells via Gs receptors
- when glucose is metabolised some of the ATP gets converted to cAMP and causes more insulin release
Alpha-2 agonist effect on beta cells
alpha 2 are Gi coupled –> decrease cAMP –> decrease insulin release
Astrocytes during hypoglycaemia
Protective mechanisms:
* glycogenolysis
* GABA shunt (glutamate converted back to GABA when TCA activity low –> lower metabolism)
To treat:
* don’t cause hyperglycaemia post neuroglycopenia as astrocytes depleted pentose phosphate shunt and low production of NADPH
* block NMDA
* L-carnitine for mitochondrial support
* Taurine to inhibit Ca++ channel activation
Urine osmolarity for diagnosis of CDI after DDAVP administration
UO increase >50%
if increase between 10-50% could be partial CDI or partial RDI
Diagnosis of SIADH
- euvolemic hypo-osmolar hyponatremia
- urine sodium >30mmol/L
- USG>1014 (or urine osmolarity >100 mOsm/L)
- exclude hypoadrenocorticism
