Endocrine Flashcards
Hormones
secreted into the circulation in very small amounts to produce a biologic effect at distant target organs or cells
Role of the Endocrine System
Regulates secretion of hormones from several peripheral organs under direction of hypothalamus (HPT) in concert with the hypophysis or pituitary gland
Hypothalamus
small area located in ventral aspect of diencephalon flanking each side of third ventricle, almost directly above the caudal pharynx
Pituitary Gland
- Located just below hypothalamus, connected via infundibular stalk
- Adenohypohysis/anterior pituitary = 3 parts
- Posterior Pituitary/Neurohyphophysis = 2 parts
- circumventricular organ
Parts of the Adenohyphophysis
3 parts
1. Pars tuberalis
2. Pars Intermedia
3. Pars distalis
Parts of Neurohyposis
- Infundibular stalk
- Pars Nervosa
Function, role of Adenohypophysis
✧ Functions like a true endocrine gland, producing and secreting hormones that target pancreas, thyroid glands, adrenal glands, reproductive organs, and the intestine
✧ Secretion by AP controlled by releasing hormones from HPT, feedback (usually negative) from serum levels of hormones produced by target tissues, ex thyroxine, cortisol, others
Function, role of Neurohypophysis
✧ Not a typical endocrine gland, actually an extension of HPT, composed of axons of neurons located in supraoptic, paraventricular nuclei of HPT that extend into pars nervosa
✧ Release hormones produced in HPT (oxytocin, vasopressin) into venous circulation of PP
✧ Primarily a conduit between HPT, peripheral circulation
Function, role of Neurohypophysis
✧ Not a typical endocrine gland, actually an extension of HPT, composed of axons of neurons located in supraoptic, paraventricular nuclei of HPT that extend into pars nervosa
✧ Release hormones produced in HPT (oxytocin, vasopressin) into venous circulation of PP
✧ Primarily a conduit between HPT, peripheral circulation
Exception to control of endocrine function by HPA?
PTH secreted in response to serum [Ca] NOT via circulating horses
Role of the hypothalamus
monitors homeostatic parameters, serum concentrations of numerous substances; secretes ‘releasing’ or ‘inhibiting’ hormones into special portal circulation connected directly to AP, and/or activates neurons that stimulate secretion of hormones into peripheral circulation via pars nervosa of PP
How Hormones Interact with Targets
- Cross cell membranes without assistance, interact with structures inside nuclei to alter cellular function (steroids are lipophilic)
- Attach to a membrane receptor, triggering a second messenger system that activates or inhibits cellular activities to produce a biologic effect (Peptides, proteins cannot cross cell membranes)
Difference btw AP, PP
AP secretes trophic hormones that stimulate target endocrine glands to produce and secrete other hormones that directly affect tissues/cells
PP differs, secretes hormones that directly affect target tissues
Hormones
- Proteins
- Steroids
- Amines
Proteins
Proteins (corticotropin, growth hormone, insulin), Peptides (oxytocin, vasopressin)
✧ Produced as large precursor molecules → cleaved to active form, stored in secretory granules within cells
✧ Move through the circulation dissolved in plasma
Steroids
(glucocorticoids, mineralocorticoids, sex hormones)
✧ synthesized from cholesterol (liver). Not stored, but synthesized/released as needed
✧ transported bound to specific carrier molecules
Amines
DOP, melatonin, epi
Pancreas
Nodular, bilobed gland within mesentery at angle where duodenum meets stomach
Dog = 2 pancreatic ducts, cats = 1
Diabetes Mellitus in Dogs
Deficiency in insulin secondary to β cell destruction (same as type-1 DM in people)
✧ High-risk breeds: Australian Terrier, Miniature/Standard Schnauzers, Samoyed, Miniature/Toy Poodles, Cairn Terrier, Keeshond, Bichon Frise, Finnish Spitz
✧ Female > Male
✧ 4-14 y.o (most frequently diagnosed 7-10 y.o)
Basic Mechanism of DM
Inadequate insulin secretion or response to control hyperglycemia
Diabetes Mellitus in Cats
Insulin resistance, eventual exhaustion of β cells (same as type-2 DM in people)
✧ No high-risk breeds (maybe Burmese)
✧ Obesity is the risk factor
✧ Male > Female
✧ 10-13 y.o
Clinical Signs of DM
due to inability of cells to utilize carbohydrates as metabolic fuel = hyperglycemia
When [Glu] in plasma exceeds renal threshold for proximal tubular reabsorption of Glu from filtrate…
✧ glucosuria (osmotic diuresis) → PU/PD
✧ Threshold; 200 mg/dL in dogs, 250-300 mg/dL in cats
Polyphagia, weight loss
Cataracts (dog)
Cats with chronic DM develop a peripheral neuropathy = plantigrade posture (10% of cats)
BW Changes with DM
⮚ Hyperglycemia, Glucosuria,
⮚ +/- increased WBC secondary infection, liver enzymes, hypercholesterolemia, azotemia in dehydrated patients
⮚ Potential electrolyte disorders: hypokalemia, hyper-/hyponatremia, hypophosphatemia, hypochloremia
⮚ Blood gas in DKA may low HCO3- and high AG
Monitoring of BG
Glu curves or fructosamine (poor control if greater than 500mg/dL)
✧ Poor reliability of Glu curves for predicting glycemic control
Complications of DM
- atherosclerosis: decreased organ blood flow, ischemia
- hypertension: retinal hemorrhage, hypertensive encephalopathy, impaired autoregulation of renal/coronary/cerebral circulations enal failure
- retinopathy: DT cerebral vascular impairment
- Nephropathy: hypertension, RF
Consequences of Peripheral Neuropathy of DM
Prolonged locoregional block
Prolonged or Shortened NMB - presence of nAChR
Increased risk of further nerve injury
Consequences of Autonomic Neuropathy
Gastroparesis
Hypotension
Poor vasomotor tone
Resp depression
Impaired thermoregulation
Cardiac failure/arrest
Anesthetic Management of DM Patients
only well-regulated diabetic patients should be anesthetized, because patients with unregulated diabetes can have marked fluctuation of [Glu]
✧ Exception: intact females with insulin resistance that require OVH before control
✧ Timely monitoring of [Glu], appropriate intervention (dextrose or insulin) are key to prevent hyper and hypoglycemia
Anesthesia of DKA Patient
stabilize as much as possible beforehand
✔ [Glu] < 400 mg/dL and control of fluid and acid- base status
LJ Guidelines for DM Management
- Overnight fast
- No insulin if BG <100mg/dL, 1-5% dextrose infusion
- BG 100-200, 1/4 regular dose +/- dextrose infusion
- BG >200 = 1/2 usual AM dose, withhold dextrose
Timing of DM Cases Undergoing Anesthesia
performed as soon as possible in morning after first [Glu] measurement
✧ Reduces need for long period of fasting, allows patient to resume normal activity more rapidly
✧ Continued insulin administration during preoperative fasting potentially increases the risk of hypoglycemia
✔ But… insulin activity important even during fasting to allow tissue uptake of nutrients
Stress Assoc with Surgery in the Diabetic Patient
Stress associated with anesthesia and surgery causes release of hormones such as corticosteroids, catecholamines
Promotion of glycogenolysis, gluconeogenesis, and ketogenesis, all of which increase insulin requirement
DM and NMBA
No absolute drug contraindications are imposed in diabetic patients
Drugs with rapid elimination or that can be reversed may allow diabetic patient to resume a normal feeding, insulin schedule sooner following anesthesia
NMBA:
Vecuronium reported to have shorter DOA in patients with DM
Rocuronium; higher rate is required than normal dog
Intraoperative BG Monitoring
–Ideally keep btw 150-250mg/dL
–[Glu] will fluctuate: affected by type/complexity of sx, prep glucocorticoid admin, presence of infection
–Frequent Perioperative monitoring Q30-60’
–No dextrose if >250mg/dL in dogs, >300mg/dL in cats
Diabetics and Hypertension
risk factor for hypertension in dogs (but not in cats), may be on medication to decrease blood pressure – this could promote hypotension under anesthesia
✧ +/- hypovolemic due to osmotic diuresis – further promoting hypotension, measure BP
Hyperglycemia or hypoglycemia can result in prolonged anesthetic recovery, CNS dysfunction and DKA
✧ Should return to routine insulin schedule after sx
DKA
✧ Dehydration, vomiting, tachypnea, hypothermia
✧ Glucosuria, ketonuria, acidosis, hyperglycemia
✧ Severe volume loss = increased AG
✧ SID = Na-Cl –> decreased SID = acidosis, loss of Na with diuresis
✧ AG = (Na+K) – (Cl+HCO3): increased DT accumulation of organic acids
Electrolyte Abnormalities Seen with DKA
✔ Hypokalemia: diuresis, acidosis, binding to ketones
✔ Hypophosphatemia: diuresis, acidosis
✔ Hyponatremia: diuresis, vomiting, binds to keto-acids
✔ Hypomagnesemia
Anesthetic Management of DM Cases
–Balanced protocol including locoregional techniques (**avoid in neuropathic limbs)
–Minimize catecholamine surges
–Hypertension: glomerulosclerosis, proteinuria
–Hypertension secondary to atherosclerosis, impaired VD, electrolyte abnormalities thickening of vascular endothelium IRT elevated levels of glucose by-products
–Hyperglycemia, vascular damage can impair cerebral response to CO2 –> cerebral ischemia (impaired vasodilation in response to hypercarbia)
Use of Dexmedetomidine in DM patients
✧ Insulin inhibition from α2A
✧ Decreased sympathetic tone (decreased stress-related hyperglycemia)
But if don’t have insulin already, does it matter?
Insulinoma
⮚ Functional tumor of pancreatic beta cells that constitutively secretes insulin, unresponsive to changes in BG
⮚ Chronic hypoglycemia, accompanying clinical signs
⮚ Uncommon tumor seen in middle aged/older dogs; rare in cats
⮚ Almost always malignant, tend to occur in either limb of pancreas rather than in body, most have metastasized at time of diagnosis
CS Insulinoma
seizures, collapse, weakness, tremors, ataxia, etc
Diagnosis of Insulinoma
⮚ Hypoglycemia
⮚ Diagnosis depends on demonstration of fasting hypoglycemia with an inappropriately high serum concentration of insulin
⮚ Insulin: glucose ratio no longer recommended
⮚ Should perform imaging prior to surgery: ultrasound, CT, thoracic radiographs
Surgical Tx Insulinoma
⮚ Surgical removal; rarely curative –> metastasis to LN, liver common
⮚ Partial pancreatectomy improves survival
✧ Average survival rates in dogs range from 7 to 42 months
⮚ depending on the stage of disease and response to surgical treatment
Medical Management of Insulinoma
–Small, frequent meals with frequent BG checks
–Do not fast longer than 8hr
–Avoid dextrose boluses unless hypoglycemic crisis = more secretion of insulin
–Glucagon: help stabilize BG concentrations
–Steroids: antagonize insulin, increase gluconeogenesis
–Diazoxide
Diazoxide
benzothiadiazide that reduces insulin secretion by preventing closure of K+-ATP channels on beta cell plasma membrane, preventing depolarization of cell
Anesthetic Management of Insulinoma
–Do not fast >8hr
–Target BG 50-60 mg/dL
–Preoperative hypoglycemia can also be managed with IV glucagon 5-40 ng/kg/min following a bolus of 50 ng/kg IV and/or dextrose infusions
–Monitor BG Q30-60’, maintain BG within range for patient
–Potential for neuroglycopenia=BAD
–Tumor manipulation: insulin release, sudden drop in insulin
–Avoid dextrose boluses, risk of rebound hypoglycemia
–Ensure appropriate pain control, minimize stress: sympathetic stimulation can cause hyperglycemia with tumor stimulation resulting in insulin secretion and rebound hypoglycemia
Dexmedetomidine for Insulinoma
helpful (bolus + CRI), better maintains BG throughout surgery
✧ Inhibits insulin release from beta cells
Post Op Complications of Insulinoma
Pancreatitis = second most common complication of partial pancreatectomy in patients with Insulinoma
Maintain normotension, normoxemia
May become hyperglycemic after surgery – due to atrophy of normal beta cells
May continue to be hypoglycemic after surgery to due metastasis of tumor or residual tumor cells left behind that continue to secrete insulin
Duodenal necrosis due to vascular compromise, ventricular arrhythmias, CNS dysfunction secondary to prolonged hypoglycemia
Neuroglycopenia
Shortage of glucose in the brain - cerebral dysfunction, death
Brain cannot store glucose
Pancreatitis
Occurs in both dogs, cats when digestive enzymes activated within pancreatic acinar cells
Pancreatic enzymes normally maintained as inactive forms called zymogens, sequestered in granules within acinar cells
✧ When defense mechanisms overwhelmed, zymogens activated = autodigestion of pancreas
Autodigestion leads to inflammatory infiltration of the pancreas and surrounding tissues
Causes of Pancreatitis in Dogs, CS
Ingestion of high‐ fat meals, various drugs, pancreatic trauma, pancreatic ischemia, pancreatic duct obstruction, and infection
depression, abdominal pain, fever, anorexia, vomiting, and diarrhea
Causes/CS of Pancreatitis in Cats
hepatobilliary inflammation +/- inflammatory bowel disease
CS obscure, vague
Acute Pancreatitis
sometimes clinically very severe, but typically does not result in chronic changes to pancreas
Chronic Pancreatitis
often clinically vague, especially in cats, but results in irreversible changes to pancreas, including atrophy and fibrosis
Incidence of Pancreatitis
✧ Middle aged and older dogs and cats
✧ Miniature Schnauzers = highest rate; Shelties, Yorkies, Poodles over-represented
Diagnosis of Pancreatitis
⮚ CBC: inflammatory leukogram
⮚ Chem: may show signs of dehydration , hyperbilirubinemia
⮚ Pancreatic lipase immunoreactivity + US, pancreatic aspirates useful
Treatment of Pancreatitis
⮚ Supportive care and pain management
⮚ Fluid therapy, vomiting drugs should receive anti-emetics (Maropitant = anti-emetic of choice)
✧ Metoclopramide? may decrease gut perfusion
✧ 5HT3 antagonists (ondansetron and dolasetron) may be helpful
✧ Feed a low-fat food
Iatrogenic Pancreatitis
⮚ induced by drugs: corticosteroids, NSAIDs, organophosphates, thiazide diuretics, sulfonamides, tetracycline, azathioprine, furosemide and estrogen
Surgical Intervention with Pancreatitis
acute necrotizing pancreatitis, pancreatic abscess, pancreatic/bile duct obstruction, or evidence of infection or neoplasia or other mass lesions, fail to respond to medical therapy
Anesthetic Management of Pancreatitis
Humans: opioids cause contration of sphincter of Oddi
Avoid premedication that may cause vomiting
Avoid α-2 agonists due to CV effects, hyperglycemia, hypoinsulinemia
⮚ Propofol associated with development of pancreatitis in humans
⮚ Halothane not recommended in compromised patients, those with concurrent liver disease, or those with cardiac dysrhythmias - isoflurane or sevoflurane preferred
⮚ In patients without coagulopathy, dermatitis, or sepsis, epidural administration of morphine provides good pain relief; used in addition to IV administration of other μ opioids
⮚ Monitor in all the normal ways – maintain normotension and normoxemia
Adrenal Gland
- Central Medulla (ANS)- from neural crest tissue of embryonic ectoderm
- Outer cortex (endocrine organ) - mesoderm, 3 layers
–Zona glomerulosa - secretes mineralocorticoids (aldosterone)
–Zona fasciculata - secretes glucocorticoids (cortisol in dogs, cats)
–Zone reticular - secretes sex hormones
GFR = SALT, SUGAR, SEX
Adrenal Gland Medulla
densely innervated with preganglionic sympathetic fibers, considered part of ANS
⮚ Main cell type = chromaffin cell, produces EPI/NE, important in emergent/stressful circumstances
Addison’s Disease
HYPOadrenocorticism
⮚ Diminished function of adrenal cortex, usually immune-mediated destruction
⮚ Can also result from pituitary adrenocorticotropic hormone (ACTH) deficiency or iatrogenic following treatment for Cushing’s disease or when a high dose steroid is abruptly withdrawn
⮚ Dogs present for complications of deficiency in both aldosterone, cortisol - F>M, mean age 4yo
Dog Breeds Predisposed to Addison’s Dz?
Standard Poodles, West Highland White Terriers, Bearded Collies, Nova Scotia Duck Tolling Retrievers, Great Danes, Rottweilers, Portuguese Water Dogs, and Leonbergers
Clinical Signs, Bloodwork Findings Assoc with Addison’s Dz
⮚ Glucocorticoid deficiency; Anorexia, lethargy, vomiting, diarrhea, weight loss
⮚ Mineralocorticoid deficiency; Hyperkalemia, hyponatremia, dehydration, azotemia, hypotension, bradycardia, collapse
⮚ CBC –Lack of a stress leukogram
⮚ ACTH Stimulation is used for diagnosis
Treatment for Addison’s Disease
- Steroids = fludrocortisone, prednisone
- For very sick patients: fluid therapy, tx hyperkalemia
Treatment Hyperkalemia
- Replacement of Crystalloid Fluids
- Calcium gluconate 10% solution
- Regular Insulin
- Dextrose
- NaHCO3
Use of Crystalloid Fluids in Tx Hyperkalemia
Dilution of K, diuresis
Admin shock dose (90mL/kg) in 1/3-1/4 aliquots and reassess K btw doses
Role of Ca Gluconate in Tx Hyperkalemia
0.5-1.5mL/kg over 10-20’
Cardioprotective: increases threshold potential, restores potential difference
Does not actively lower potassium: temporarily protects heart
Role of Dextrose in Tx Hyperkalemia
0.5-1mL/kg bolus followed by dextrose CRI
Stimulates endogenous insulin secretion, maintains BG following insulin administration
Also addresses hypoglycemia common with Addison’s
Role of Regular Insulin in Tx Hyperkalemia
0.25-0.5U/kg IV or IM with dextrose bolus - 4mL 50% per unit insulin
Stimulates transport of glucose and K into cells
Rapid onset, montior BG levels
Role of NaHCO3 in Tx Hyperkalemia
Increase pH so K moves into cell in exchange for hydrogen to maintain electrochemical balance
Slower onset of action, 1h for distribution of bicarbonate
Main Consideration of Ax Management of Addisonian Patient
inappropriate responses to stress; consequently, glucocorticoid doses should be adjusted before surgery/anesthesia IOT prevent adrenal crisis, refractory hypotension in perioperative period
Recommended: extra dose of steroid before anesthesia in addition to their normal daily dose
–Ex Dex SP 0.25mg/kg, predisolone 2mg/kg, hydrocortison 0.5mg/kg
Postoperatively, additional glucocorticoids administered PRN
Other Considerations of the Addisonian Patient
If unstable patients taken to surgery, evaluated for hyperkalemia, hypovolemia, hyponatremia, azotemia, metabolic acidosis, hypoglycemia - managed prior to anesthesia
Etomidate avoided: inhibits 11β-hydroxylase, enzyme necessary for synthesis of cortisol in dogs, cats for 2 -6 hours after administration
Monitor all the normal things with close attention to blood pressure as hypotension common in these patients
Addisonian Crisis
previously undetected or otherwise well-controlled hypoadrenocorticism if cortisol levels insufficient for increased demand
May present in hypovolemic shock, with concurrent metabolic acidosis, hypoglycemia, hyperkalemia, hyponatremia.
Critical Illness Related CorticoSteroid Insufficiency
Critically ill patients who develop relative corticosteroid insufficiency as a result of decreased production, altered metabolism, and impaired response to circulating cortisol concentrations
–Severe hypotension, refractory to fluid and vasopressor support
With septic shock, severe trauma, GDV
Diagnosis in people; ACTH stimulation test with a change in cortisol concentration < 9 μg/dL
Administration of CS in patients may prove beneficial in helping reestablish homeostasis
Cushing’s Syndrome
HYPERadrenocortism
excess circulating concentrations of cortisol
Atypical Addison’s
Form of disease where signs of only cortisol deficiency seen
Atypical Form of Cushing’s
excess secretion of sex hormones
Forms of Cushing’s Dz
- Pituitary Dependent
- Adrenal Dependent
- Atypical
- Iatrogenic
Pituitary Dependent HAC
80 – 85% of naturally occurring cases, increased secretion of ACTH from adenoma of corticotropes of pars distalis of pituitary resulting in bilateral adrenocortical hyperplasia, excessive cortisol secretion
Adrenal Dependent HAC
less common; results from a cortisol secreting tumor of the adrenal gland
Adrenal Dependent HAC
less common; results from a cortisol secreting tumor of the adrenal gland
Clinical Signs of HAC
⮚ Bilaterally symmetrical alopecia, comedones, dermal hyperpigmentation, dermal/ muscle atrophy, PU/PD, polyphagia, pendulous abdomen, hepatomegaly, panting hypertension, lethargy
⮚ No gender predilection for pituitary dependent disease; adrenal dependent F>M
⮚ Poodles, Boston Terriers, German Shepherds, Dachshunds, Beagles predisposed
Blood Work Assoc with HAC
⮚ Stress leukogram
⮚ Increased alkaline phosphatase, increased ALT, hypercholesterolemia, hyperglycemia
Tx HAC: mitotane
–Necrosis of deeper zones of adrenal cortex, sparing superficial mineralocorticoid producing zone
–AKA necrosis of zona fasciculata, zona reticularis
Tx HAC: trilostane
reversible, competitive inhibition of 3β-hydroxysteroid dehydrogenase, enzyme necessary for production of cortisol, aldosterone, androgens in adrenal cortex
–Blocks synthesis of circulating cortisol, aldosterone
TX HAC: ketoconazole
–Imodazole anti fungal that inhibits synthesis of GC/androgens
–Lowers circulating cortisol levels via inhibition of stereo genesis but has minimal effect on MC production
Selegiline/L-Deprenyl for Tx HAC
–DOP: inhibitory NT of ACTH secretion in pars intermedia
–Irreversible inhibition of monoamine oxidase type B –> helps restore central dopamine [ ], facilitates dopaminergic transmission
–Control of PDH
Anesthetic Management of HAC
–Require GA for other concurrent dz, ADH for adrenalectomy
–with PDHC treated with mitotane or trilostane may lack adequate functional adrenocortical reserve and may not handle stressful anesthetic or surgical events appropriately – post ACTH stimulation cortical [ ] 2-5mcg/dL –> lower should be managed as iatrogenic Addisonian
Hypercoag State with HAC and Ax
⮚ Both forms of HC predisposed to hypertension, thrombus formation
⮚ Anti-thrombotic therapy may be indicated
✧ Monitor APTT; goal = increased 1.5 to 2 fold, no greater
⮚ Should perform blood typing, cross matching if significant bleeding expected
⮚ Select drugs that will have the patient walking within 4 hours of recovery to help decrease thrombus formation
greater risk of thromboembolic events so watch for signs of PTE: dyspnea, tachypnea, cyanosis, collapse
Other Features of HAC Patient undergoing GA
⮚ NSAIDs are often avoided due to concern for GI ulceration
⮚ These patients will commonly hypoventilate under anesthesia due to respiratory muscle weakness, increased abdominal fat, hepatomegaly, and bladder distension
⮚ Dexamethasone should be administered postoperatively to adrenalectomy patients to prevent development of hypoadrenocorticism
LDDST
No change in cortisol with ADH, +/- cortisol suppression with PDH
ACTH Stim
Increased cortisol with PDH bc ACTH goes to the adrenal glands and stimulates cortisol production
Low with ADH DT negative FB of cortisol on AP - AP STILL responsive to fb from cortisol
HDDST
ADH = HONEYBADGER!!! No change
Cortical suppression with PDH bc AP still responsive to negative fb
MOA Hypercoagulability of HAC Patients
Increased EPO (increased PCV), increased blood viscosity
Increased clotting factors
Increased Antithrombin III –> increased risk DVT, PTE
Effects of HAC on Resp System
Decreased FRC, hepatomegaly
Ca deposition at level of pulmonary interstitum, bronchial level
Decreased Oxygenation, hypoventilation –> preoxygenation, IPPV
Dx HAC
✧ ACTH Stim
✧ Low Dose Dex Supression
✧ Urine cortisol:creatinine ratio
✧ Dexamethasone-supressed urine cortisol:creatine ratio
✧ No test is perfect – false positive is common
Pheochromocytoma
Catecholamine secreting tumor that arises from chromaffin cells of adrenal medulla
Clinical Signs
⮚ Often intermittent and paroxysmal due to episodic release of catecholamines
✧ Weakness, collapse, tachypnea, tachyarrhythmia, hypertension, and seizures
Diagnosis Pheo
⮚ Difficult
⮚ Bloodwork sometimes indicates signs of excess catecholamines
⮚ Plasma and urinary metanephrines used in humans
⮚ Definitive diagnosis is made via biopsy/aspirates of the tumor
⮚ The origin, architecture, vascularity, invasiveness of mass best determined on CT/ MRI
⮚ Invasive PHEOs reported to affect vena cava, aorta, renal veins, hepatic veins
Anesthetic Management of Pheo
Prolonged medical management to stabilize patients prior to surgical excision ideal
✧ Phenoxybenzamine – long acting, non-competitive, non-selective α adrenergic receptor antagonist
✔ Started at a low dose, increased until signs of hypotension are present
✔ Decreases mortality rate from 43% to 13%
✧ Likely due to decreased vasoconstriction and improvement of intravascular volume
Arrhythmia Management with Pheo
Atria, ventricular tachycardias, AVB occur w
✧ Can treat with β blockers
✧ DO NOT START β BLOCKER UNTIL PHENOXYBENZAMINE HAS BEEN STARTED
✔ This will result in unopposed α agonism and exacerbate hypertension
✧ Myocardial damage can occur due to these arrhythmias so an echo is warranted prior to anesthesia
Management of Hypertension - Pheo
Nitroprusside: dilates arterioles, veins via NO release - BP monitoring
Phentolamine: short acting alpha blockade
MgSO4: direct inhibition of catecholamine R, release from nerve terminals; VD
refractory hypotension - pheo
phenylephrine
Vasopressin
Triggers for Pheo Crisis
Stress
Ax Induction
Histamine release: morphine, meperidine, atracurium
Elevated PCO2
Tumor Manipulation
Increased intraabdominal pressure: bladder expression, abdominal insufflation
Drugs that cause SNS Stimulation
Des
Halothane
Ephedrine
N2O
Metoclopramide
Glucagon
Succ
Thyroid Gland
Two lobes, one on each side trachea, may be connected via an isthmus
Distal to larynx, ventrolateral to trachea, extends from fifth to eighth tracheal rings
Composed of follicles lined by epithelial cells that produce, secrete hormone
Major Thyroid Hormones
triiodothyronine (T3), tetraiodothyronine (T4) aka thyroxine
T3 = active, T4 = inactive
Regulation of thyroid hormone release
⮚ TSH from anterior pituitary controls thyroid hormone production, which is controlled by TRH of hypothalamus
⮚ T3 + T4 are secreted into circulation, highly plasma protein bound
⮚ Feedback for TRH production is from a combination of extrinsic and intrinsic factors, including negative feedback from T3 and T4
Hypothyroidism
Immune-mediated disease caused by lymphocytic infiltration of thyroid gland with eventual destruction of functional thyroid tissue
Clinical Signs Hypothyroid
Weight gain, hair loss, dry skin and hair coat, decreased activity
Myxedema may occur – abnormally high amounts of mucin accumulate in the skin and other tissues
Large breed dogs more predisposed:
⮚ Doberman pinschers, Great Danes, Irish Setters English Setters, and Golden Retrievers
⮚ No gender predilection
Bloodwork Assoc with Hypothyroidism
Hypercholesterolemia, Hypertriglyceridemia, mild normocytic normochromic anemia (decreased erythropoiesi, bone marrow response from thyroid hormone deficiency)
Decreased GFR attributed to VC of afferent/efferent arterioles via impaired NO release from endothelial cells, decreased CO from lowered metabolic rate
Total T4, free T4 and free T4Eq : euthyroid sick vs hypothyroid
Treatment for Hypothyroidism
Levothyroxine supplementation: 8 wks of tx resolves most alterations of peripheral circulation, muscle activity, and CV signs
Respiratory Effects of Hypothyroidism
PPV likely required: muscle weakness, poor to obese BCS (decreased compliance, decreased FRC)
Decreased sensitivity to hypoxemia, hypercapnia
Anesthetic Considerations with Hypothyroidism
⮚ Ideally pt should be euthyroid; mild hypothyroidism not a concern
✧ MAC of halothane, isoflurane in euthyroid and hypothyroid dogs are clinically similar
⮚ Unregulated patients will have lower metabolic rate and may recover more slowly
✧ Use shorter-acting or reversible drugs
✧ Severe cases: increased morbidity and mortality (pt with mental obtundation, generalized weakness, bradycardia, hypothermia, left ventricular hypocontractility, impaired ventilation
CV Effects of Hypothyroidism
Decreased CO
Atherosclerosis
Elevated diastolic DT increased SVR - potential for decreased circulating vol
MOA of Decreased CO with hypothyroidism
✧ Decreased number, affinity of cardiac β-receptors; reduced sensitivity of myocardium to catecholamines
✧ Alterations in peripheral circulation, ability of myosin to bind to actin, calcium channel function, down-regulation of B-adrenergic receptors
✧ Common comorbidity: adrenal insufficiency
Other Considerations with Hypothyroid Patients
Hypothermia more likely
Delayed gastric emptying
✧ Pretreat with metoclopramide/PPIs/H2 blockers
✧ Rapid intubation
MOA Atherosclerosis assoc with Hypothyroidism
✧ Hypercholesterolemia and hypertriglyceridemia
✧ Can lead to decreased oxygen delivery to vital tissues
✧ Patients should be preoxygenated
Anesthetic Management of Hypothyroid Patient
⮚ Ideally 8 wks of hormone supplementation
⮚ Preoxygenate
⮚ Initiate warming therapy ASAP
⮚ Titrate drugs to effect
⮚ Ketamine favored due to SNS stimulations
⮚ Used balanced and locoregional technique; minimize inhalant requirement
⮚ Little effect of hypothyroidism on MAC
⮚ Support though recovery as this may be prolonged
⮚ Monitor glucose levels
⮚ Hypotension may respond to steroid supplementation if adrenal insufficiency is also present
Severe Hypothyroid Cases
✧ Bradycardia more difficult to reverse with anticholinergics
✧ Hypotension less responsive to ionotropes
✧ Prolonged recovery due to slow metabolism of premedication and maintenance drugs
✧ Hypothermia difficult to manage
✧ Protracted recovery
✔ Ensure normothermia and normoglycemia
✔ Oxygen supplementation, avoid hypercapnia
✔ Consider drug reversal
✔ Myxedema coma should be considered if all other parameters are WNL
✔ Treat with levothyroxine or potassium iodate IV + dexamethasone 0.25 mg/kg IV
Hyperthyroidism
most common feline endocrine disorder, rare in dogs
Signs caused by excessive circulating thyroid hormones causing pathologically high metabolism thyrotoxicosis or multi-systemic disease
Enviro causation: cat litter, excess iodine in commercial foods
⮚ May not always have elevated T4
Primarily middle-aged cats >10ys
No breed or sex predilection
Clinical Signs of Hyperthyroidism
⮚ Palpable thyroid nodule(s)
⮚ Irritable, restless hyperactive mentation, vocalization, behavioral changes
⮚ Chronic cellular malnutrition
✧ Polyphagia or “pica”, weight loss, poor body condition
✧ Rough, unkempt haircoat
⮚ Decreased GI transit times: Vomiting, diarrhea, PU/PD
⮚ Dyspnea, panting (particularly with pulmonary edema and CHF)
⮚ Cardiac murmur, tachycardia, gallop rhythm, arrhythmias, CHF
✧ Hypertension → Myocardial hypertrophy (HCM) → tachyarrhythmias
✧ Increased sensitivity to catecholamines (direct effect of T3 on myocardium)
Diagnosis of Hyperthyroidism
⮚ Thoracic radiographs: cardiomegaly, pleural effusion, pulmonary edema
⮚ Echocardiogram: cardiomegaly, left ventricular and interventricular septal hypertrophy
⮚ Total T4, free T4, free T4Eq
⮚ Thyroid scintigraphy
Clinicopathologic Changes Assoc with hyperthyroidism
⮚ Increased GFR
✧ Can mask underlying renal disease
✧ Increases in both BUN & creatinine is sign of concurrent renal disease
✧ Can have increased BUN only from increased protein catabolism
⮚ Erythrocytosis
⮚ Elevated ALT, ALP, LDH (hepatocellular stress)
⮚ 20-40% cats will have mild elevations in renal values (unmasking occult renal dz when treated)
Treatment for Hyperthyroid
⮚ Methimazole
⮚ Radioiodine therapy
⮚ thyroidectomy
Thyrotoxic Storm
Sudden massive release of thyroid hormones
o Tachycardia, arrhythmias, hypertension, hyperthermia, CHF, GI/CNS signs
Tx:
beta blockers: esmolol 0.02-0.05mg/kg IV + CRI 50-100mcg/kg/mib
VD: nitroprusside, magnesium
Supportive tx: cooling, fluids, IPPV
Most commonly seen with long standing undiagnosed severe HT
Anesthetic Considerations for Hyperthyroid: CV
Often have concurrent thyrotoxic HCM (diastolic dysfunction); hypertension, dysthymias, cardiac arrest
✧ Maintain low-normal HR, adequate preload- improved diastolic filling and myocardial blood flow
✧ Increased sensitivity to circulating catecholamines- up regulation, increased affinity of beta-adrenergic receptors
✧ HOCM cats can benefit from dexmedetomidine- decreases gradient across outflow tract, resolving obstruction
Avoid increases in myocardial VO2, hypertension, tachycardia and arrhythmias
✧ Avoid anticholinergics, keta, N2O, desflurane, stress!
✧ ACP may be helpful in cases without concurrent HCM
Other Anesthetic Considerations for hyperthyroid
Prone to hypoxemia and hypercarbia due to increased metabolic rate
✧ Preoxygenation and ventilation
Weight loss- altered volume of distribution, hypothermia
✧ Can have rapid development of both hypothermia and hyperthermia under anesthesia
Difficult to handle, AGGRESSIVE
Muscle weakness- increased work of breathing
Renal dysfunction unmasked once euthyroid
Anesthetic Management for hyperthyroid patients
⮚ Poor anesthetic candidates- elderly, fragile, cachectic with multiple comorbidities
⮚ Minimize stress to prevent catecholamine release
⮚ Euthyroidism after 2-4 wks od treatment is greatest contributor to minimizing mortality
⮚ Ensure medications continued on day of surgery
+/- thoracocentesis if pleural effusion, diuretic if pulmonary edema
Avoid SNS stimulation - pain, drugs, etc
No change in MAC value, although decreased CO will slow induction with inhalant
Maintain renal perfusion
Treat dysrhythmias early
Options for Management of Uncontrolled Hyperthyroid
few days of beta-blockers therapy reduces mortality associated with CV system (unless CHF)
✧ Atenolol 0.625 mg per cat per day
✧ Propanalol 2.5-5 mg PO BID or TID
✧ Goal= HR < 120bpm
Thyroid Neoplasm in Dogs
-Non-functional, but can be very locally invasive
-Larynx, trachea, cervical muscles, nerves, esophagus
-Pulmonary metastasis also common
Clinical Signs of Thyroid Neoplasia in Dogs
airway obstruction/compromise, dyspnea, cough, vomiting, dysphagia, anorexia and weight loss
Anesthetic Management of Thyroid Neoplasia
AIRWAY MANAGEMENT
⮚ Potent sedatives (dexmedetomidine) can produce intense neck muscle relaxation and exacerbate airway obstruction
⮚ Should not be left unattended after sedation
⮚ Preoxygenation if the patient allows
⮚ Rapid induction and intubation
⮚ Tracheostomy supplies should be available
⮚ Reintubation supplies should be ready at extubation
⮚ Monitor for signs of hypocalcemia following bilateral thyroidectomy
Parathyroid Gland
Four in dogs in cats - two embedded in cranial pole of each lobe of thyroid, two external to gland
Main function: production, secretion of PTH IRT Ca concentrations (chief cells)
PTH
⮚ Stimulates activity of osteoclasts to reabsorb bone
⮚ Encourages absorption of calcium from the GI tract via the activated form of vitamin D
⮚ Discourages excretion of calcium in the urine
In face of excessive PTH…
calcification of soft tissues occurs with resultant dysfunction of the affected structures of organs
Pathophysiology of Hyperparathyroidism
Uncommon disorder of middle-aged and older dogs, rare in cats
In most cases caused by a singular benign adenoma of an extracapsular parathyroid gland
Autonomously secrete PTH causing hypercalcemia
Usually no clinical signs – will not hypercalcemia on bloodwork
Diagnosis of Hyperparathyroidism
ionized hypercalcemia, a low or low-normal serum phosphorus concentration, an inappropriately high concentration of PTH
Treatment for Hyperparaythroidism
⮚ Surgical removal is curative
⮚ Can also do US guided ablation using heat or ethanol
⮚ Post-operative complication: hypocalcemia – develops upon withdrawal of PTH secreting tissue; remaining non-adenomatous glands atrophied due to chronic hypercalcemia
Warrants treatment if iCa <1.5mmol, 6mg/dL
Anesthetic Management of Hyperparathyroidism
Manage hypercalcemia first; should delay surgery until total calcium is less than 15-16mg/dL (>3.75-4mmol/L)
✧ IV fluids (saline)
✔ Some patients will be hypovolemic due to PU/PD so this will also replace volume
✧ Furosemide
✧ Steroids
✧ Calcitonin
✧ Bisphosphonates
✧ Bicarbonate can be used in cases of life-threatening hypercalcemia as it will cause the calcium to rapidly bind to albumin
Anesthetic Management of Hyperparathyroidism
⮚ Manage hypercalcemia first; should delay surgery until total calcium is less than 15-16mg/dL (>3.75-4mmol/L)
✧ IV fluids (saline)
✔ Some patients will be hypovolemic due to PU/PD so this will also replace volume
✧ Furosemide
✧ Steroids
✧ Calcitonin
✧ Bisphosphonates
✧ Bicarbonate can be used in cases of life-threatening hypercalcemia as it will cause the calcium to rapidly bind to albumin
Other Considerations in Hypercalcemic Patients
⮚ Some of these patients may have underlying CKD caused by chronic hypercalcemia
✧ Another reason to make sure that they remain normotensive normovolemic
⮚ Hypercalcemia might be expected to antagonize the effects of non-depolarizing muscle relaxants
Also: ST mineralization
Postoperative Complications of PTH?
AIRWAY OBSTRUCTION
HYPOCALCEMIA
ECG Changes Assoc with Hypercalcemia
✧ Shortened QT interval, shorted ST segment, bradycardia, wide QRS, ST segment elevation
General Effects of hypocalcemia
Increased muscle activity/hyperexcitability: muscle tremors, seizures, arrhythmias
Effect of PTH
Increase Ca, Decreases PO4
–Direct action on bone to increase osteoclastic activity, increases release of PO4, Ca
–Kidney: activation of transport mechanisms to resorb Ca from distal tubule, decrease resorption of phosphate
–Stimulation of 1-alpha-hydroxylase: required for activation of calcitrol (active vitamin D)
Because resorption of PO4»_space;> release from bone, net effect is decrease in PO4
Effect of Calcitrol
Active form of vitamin D
Increases GI absorption of phosphorous, Ca
If Ca levels normal: inhibits PTH
Calcitonin
Opposes effects of PTH
Major effect = inhibition of osteoclastic activity
Minor effect = inhibition of renal tubular resorption of Ca so excreted into urine
Nephrogenic DI
Kidneys do not respond to vasopressin/ADH
Central DI
Pituitary does not produce ADH
Insulin
Increases fat synthesis
increases glycogen storage
Stimulates protein synthesis, amino acid uptake
Decreases protein degradation
Stimulates ATP production, gluconeogenesis
Glucagon
Secreted by pancreatic alpha cells IRT BG <80mg/dL
Primary target = liver to increase G6P, allows liver/kidney to release glucose back into the blood
Goal: prevent hypoglycemia
Catecholamines
Secreted by sympathoadrenal system IRT to sympathetic discharge (NE), autonomic stimulation of adrenal medulla (NE, EPI)
Primary target (for BG) = liver, m, adipose tissue to increase BG concentration
Stimulate glucagon secretion, inhibit insulin secretion
Glucocorticoids
Oppose action of insulin in regulation of carbohydrate, lipid, protein metabolism via effects on liver, SkM, adipose tissue
Hyperglycemic actions
Growth Hormone
Hyperglycemic/lipolytic in actions via direct antagonism of insulin
Stress response
- Alarm reaction = increased ACTH, catecholamines; increased HR, RR, BP
- Resistance Phase = increased PSNS control, decreased cortisol, HR, BP
- Exhaustion = depletion of resources
