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