Endocrine Physiology Flashcards
what area of the adrenal cortex produces the mineralocorticoids
zona glomerulosa
(outermost)
what area of the adrenal cortex produces the glucocorticoids
zona fasciculata
what area of the adrenal cortex produces catecholamines
zona reticularis
(innermost)
pituitary adrenal axis
- hypothalamus –> CRH
- anterior pituitary –> ACTH
- adrenal cortex –> cortisol
functions of cortisol
regulate metabolism, blood sugar, lipids, mucosa health, immune function
functions of the RAAS system
renin angiotensin aldosterone system
responds to LOW blood pressure
steps of RAAS activation
- low BP detected by JGA in kidneys –> kidneys release renin
- renin converts angiotensinogen (produced in the liver) into angiotensin I (ANG I)
- ACE gets released from the lungs and circulates –> converts circulating ANG I into ANG II
- ANG II stimulates release of aldosterone from the adrenal gland
- aldosterone acts on the kidneys to stimulate Na and water reabsorption to increase BP
function of aldosterone
maintain blood volume by retaining Na and excreting K to increase water reabsorption
stimulated by low BP and high K
primary addison’s disease
adrenal glands don’t produce hormones due to:
- immune mediated destruction
- drug induced destruction
- bilateral adrenalectomy
typical primary addison’s
destruction of both the zona glomerulosa and fasciculata
low cortisol & low aldosterone
atypical primary addison’s
destruction of the zona fasciculata ONLY
low cortisol & normal aldosterone
what is the expected ACTH level of a dog with primary addison’s
HIGH - trying to stimulate the adrenals
secondary addison’s
anterior pituitary does not produce ACTH due to:
- exogenous steroid administration
- hypopituitarisum (surgical removal)
cortisol and aldosterone levels in secondary addison’s
low cortisol & normal aldosterone
presents similarly as atypical primary addison’s
what is the expected ACTH level in a dog with secondary addison’s
LOW - either the pituitary is unable to produce ACTH OR it is receiving negative feedback from exogenous steroid administration
what type of addison’s disease is susceptible to developing addisonian crisis
primary typical addison’s only due to aldosterone deficiency leading to hypovolemic shock and severe electrolyte imbalance
what is the Na:K ratio of a patient with confirmed addison’s
Na:K < 27:1
hyponatremia
hyperkalemia
how does prerenal azotemia and hyperphosphatemia develop in addisonians
unable to maintain hydration –> prerenal azotemia
decreased GFR –> decreased P clearance in the kidneys –> hyperphosphatemia
normal resting cortisol
> 2.0 ug/dL
resting cortisol in a patient that should get an ACTH stim test
< 2.0 ug/dL
what cortisol level following ACTH stimulation if confirmatory for addison’s disease
< 2.0 ug/dL
what type of addisonians require DOCP injections monthly
primary typical HA
DOCP = synthetic mineralocorticoid
only needs to be replaced in aldosterone deficient patients
where is insulin produced
beta cells in islets of langerhans in the pancreas
functions of insulin
lower blood glucose by:
- promote glucose uptake by muscle and adipose cells via GLUT4
- promote glycogenesis in liver and muscles to store glucose
- inhibit gluconeogenesis in the liver
- facilitate amino acid uptake in muscles
- promote synthesis of triglycerides and inhibits lipolysis in adipose
- binds IGF-1 to promote growth
what are factors that decrease BG
insulin and exercise
inhibit glucagon –> low glucagon state –> inhibits gluconeogenesis + glycogenolysis
what are the diabetogenic hormones
hormones that oppose the effects of insulin
- cortisol
- glucagon
- epinephrine
- growth hormone
all contribute to developing insulin resistance by stimulating gluconeogenesis + glycogenolysis
pathogenesis of weight loss and polyphagia in diabetes
- glucose accumulates in plasma despite low glucose in cells due to insulin deficiency/resistance
- cells starve and require alternate energy pathways
- breakdown of muscle and fat to feed the cells
- weight loss + polyphagia
pathogenesis of glucosuria and PU/PD in diabetes
once blood glucose exceeds the renal threshold –> glucosuria –> glucose in the urine triggers PU –> triggers PD to try to keep up with urination
what are the general management strategies of diabetes in cats
diet + weight loss management in order to reduce insulin requirement
SGLT-2 inhibitors
how does exogenous corticosteroid administration in cats predispose to diabetes
cats on prednisolone –> increase cortisol –> counteracts insulin –> insulin resistance
ALWAYS monitor blood glucose levels in cats on prednisolone
hypersomatotropism
excess growth hormone resulting in acromegaly in cats
increased GH causes insulin resistance and development of diabetes mellitus
what is used to diagnose hypersomatotropism in cats
IGF-1 (acts as a proxy for growth hormone)
ALL diabetic cats should be tested for hypersomatotropism
what is the most common cause of a stable diabetic dog developing DKA
inflammation (ex. development of pancreatitis)
what is the renal threshold for glucose in dogs
180 mg/dL
can be hyperglycemic WITHOUT glucosuria
what is the renal threshold for glucose in cats
270 mg/dL
can be hyperglycemic WITHOUT glucosuria
what other biochemical changes can be seen on a chem panel in a patient with DM
- elevated liver enzymes
- hyperlipidemia (cholesterol + triglycerides)
- prerenal azotemia
- electrolyte imbalance
what are the most consistent formulations of exogenous insulin
pens + solutions
mL per unit in U40 syringe
0.025 mL
mL per unit in U100 syringe
0.01 mL
best insulin options for dogs
BID administration:
- vetsulin
- novolin
SID administration:
- tresiba (degludec)
- toujeo (glargine)
best insulin options for cats
BID:
- prozinc
SID:
- lantus
- toujeo
what are the MOAs of oral antihyperglycemics
- promote insulin secretion
- increase insulin sensitivity
- decrease glucose absorption from GIT
- promote glucosuria
SGLT2
sodium glucose transporter located in the renal proximal tubule to reabsorb glucose from the urine
SGLT2 inhibitors
blocks SGLT2 to decrease glucose reabsorption and. promote excretion
is there a risk of a cat becoming hypoglycemic on SGLT2 inhibitors
no - does not block SGLT-1 receptors so there will still be some glucose absorption
effect of SGLT2 inhibitors on BG and glucosuria
increases glucosuria by lowering the renal threshold
causes a RAPID drop in BG and transient increase in polyuria
when should SGLT2 inhibitors be used
insulin resistant diabetes ONLY
must have endogenous insulin to prevent ketosis
what should always be monitored at home in a patient on SGLT2 inhibitors
serum or urine ketones
if a cat becomes insulin deficient while on the medication - will cause ketosis
if ketones are elevated - discontinue SGLT2 inhibitor and use insulin instead
forms of SGLT2 inhibitors available in vet med
bexacat + senvelgo
used in place of insulin for UNCOMPLICATED, insulin resistant cats with risk factors
NOT for use in cats that are on exogenous insulin
most important indicators of diabetes management to monitor
clinical signs (want to resolve)
weight trends (stabilize)
what do continuous glucose monitors sample
interstitial glucose
slightly delayed behind changes in blood glucose
goal BG for adequate DM management
BG 100-200 mg/dL
nadir: low 100s
highest: remains below 300
why are cats less likely to develop DKA
cats should have some insulin production that prevents the development of ketones
dogs are insulin deficient - more likely to start producing ketones due to cell reliance on alternate metabolic pathways
what is the goal of nutritional diabetes management
improve glycemic control
does NOT eliminate the need for insulin therapy
goal of nutritional DM management in dogs
provide the same AMOUNT of the same DIET at the same TIME every day
always coordinate with insulin administration
avoid treats if possible
is there a need to change diet in dogs with DM
no - as long as the patient eats the diet well, do not need to change
exceptions:
1. fat intolerance (pancreatitis)
2. nutritionally responsive comorbidities
can add fiber if regulation is poor
is obesity related insulin resistance reversible in cats
yes with weight loss - not necessarily diet dependent as long as they lose weight
goal of nutritional management of cats with diabetes
weight loss and stabilization
overweight cats - low carb + canned diets
lean cats - moderate carb + high fiber + dry diets
consistent timing is less important than in dogs
hyperlipidemia nutritional management
fat restriction
- want a diet that is HALF the amount of fat on an ME basis than current diet
goal is fasted serum TG < 500 mg/dL
is the majority of calcium intra or extracellular
extracellular w/ 0.1% being in the ECF
what does total Ca measure
all calcium in the ECF
ionized > protein bound > complex bound
what is the most reliable measure of calcium levels
ionized Ca
what hormones regulate Ca
- PTH
- vitamin D
- calcitonin
- FGF-23
what is the primary source of Ca and P in the body
dietary intake
does calcitonin have an important role in Ca metabolism in CKD catsq
no
how can FGF-23 be used in CKD cats
early biomarker of CKD - level of elevation can guide the need for phosphate restriction or binders
most common causes of hypercalcemia in cats
renal disease
idiopathic
neoplasia
how does granulomatous disease cause hypercalcemia
macrophages secrete 1-alpha hydroxylase –> activates vitamin D into calcitriol in the kidneys –> increased active vitamin D –> increases Ca
hypercalcemia of malignancy
cancer cells secrete parathyroid hormone related protein (PTHrP) –> activates PTH receptors –> increases Ca, decreases P
what types of cancer are most commonly associated with hypercalcemia of malignancy
lymphoma
AGASACA
multiple myeloma
SCC (cats)
idiopathic hypercalcemia
mild to moderate elevations in ionized and total Ca in young to middle aged cats
usually incidentally found but can cause vomiting, weight loss, constipation
tx w/ high fiber diet, corticosteroids if clinical
