Defense & Barriers 2: (1) Endocrine Diseases of Adrenal Gland

Question 1

3 layers of adrenal gland OUTER to INNER?
what part of the adrenal gland is this?

Answer 1

ZONA…
1. GRANULOSA
2. FASCICULATA
3. RETICULARIS

ADRENAL CORTEX!!

Question 2

adrenal MEDULLA…
essential for life?
function & what does it secrete? (category name & 3 examples/species)
pathway for secretion? (2)
catabolism/secretion?
which metabolite is MORE clinically useful?
what’s true about both metabolites?

Answer 2

NOT NECESSARY FOR LIFE

= secretes CATECHOLAMINES in response to SYMPATHETIC STIMULATION (fight or flight)

3 examples?
1. EPINEPHRINE = DOGS
2. NOREPINEPHRINE = CATS
3. DOPAMINE = a little made by DOGS/CATS

catecholamine secretion pathway?
1. TYROSINE HYDROXYLASE converts TYROSINE into NOREPINEPHRINE
2. NE acts as a negative feedback mechanism to inhibit TYROSINE HYDROXYLASE

catecholamines are metabolized & secreted as…
1. Metanephrine
2. Normetanephrine
NORMETANEPHRINE **MOST CLINICALLY USEFUL because it helps us determine if catecholamines are being SECRETED IN EXCESS

Both ONLY HAVE A SHORT HALF-LIFE, don’t want fight or flight to last too long

Question 3

adrenal CORTEX…
essential for life?
function & what does it secrete from VARIOUS LAYERS? (3 categories, 1 –> 2 –> 1)
what is the pathway for secretion called?

Answer 3

ESSENTIAL FOR LIFE!

secretes…
1. From all 3 layers…
–> CORTICOSTERONE
2. From zona RETICULARIS & FASCICULATA
–> CORTISOL
–> SEX HORMONES
3. From zona GLOMERULOSA
–> MINERALOCORTICOID

pathway for secretion = STEROID SYNTHESIS

Question 4

steroid synthesis…
occurs WHERE?
what hormone is the ORIGIN of all others?
dog/cat steroid synthesis?
what’s unique about the ENZYMES in this pathway? (2)

Answer 4

occurs in ADRENAL CORTEX?

origin?
–> WITHOUT CHOLESTEROL, WE DIE!!! ALL STEROID HORMONES ORIGINATE WITH THIS

dog/cat steroid synthesis?
1. Dogs make an EQUAL AMOUNT OF CORTICOSTERONE & CORTISOL
2. Cats make MOSTLY CORTISOL

Enzymes used in this pathway…
1. can be RESTRICTED TO A CERTAIN LAYER
2. can be RECYCLED

Question 5

ALDOSTERONE is produced from ____

Answer 5

CORTICOSTERONE

Question 6

17-alpha hydroxylase
what is it NECESSARY for?
where is it NOT present?

Answer 6

= necessary for synthesizing ANDROGENS and NOT PRESENT IN ZONA GLOMERULOSA in ADRENAL CORTEX

Question 7

what ENZYME is present in the zone GLOMERULOSA & what does it produce?

Answer 7

ALDOSTERONE SYNTHASE, ALDOSTERONE

Question 8

effects of ACTH on steroid synthesis? (3, including what it does, how it does it, and net result)
effects of ANGIOTENSIN II on steroid synthesis? (2)

Answer 8

ACTH?
1. = increases CONVERSION of CHOLESTERYL ESTERS to FREE CHOLESTEROL and PREGNENOLONE
2. does this via increasing SYNTHESIS OF P450 ENZYMES
3. results in net increase in SYNTHESIS & SECRETION of cortisol!

ANGIOTENSIN II?
1. INCREASES conversion of CHOLESTEROL to PREGNENOLONE
2. INCREASES ALDOSTERONE SYNTHASE activity to make MORE aldosterone

Question 9

epinephrine/norepinephrine effects…
what are they mediated by?
function?
what do they INCREASE? (7)
what do they DECREASE? (1)

Answer 9

EP/NOREP?

= mediated by ALPHA & BETA ADRENERGIC RECEPTORS

function?
= mimic effects of adrenergic nervous system –> THINGS WE DO IN FIGHT OR FLIGHT

increases…
1. HR
2. Excitability
3. force of myocardial contractility
4. alertness
5. Metabolic rate
6. Glycogenolysis (hyperglycemia)
7. Lipolysis

decreases = PERIPHERAL RESISTANCE

Question 10

what is a permissive effect?

Answer 10

the PRESENCE OF ONE HORMONE will ENABLE ANOTHER HORMONE to act

Question 11

glucocorticoids…
what does it DO/BIND?
its effect on 3 other hormones?
effects from TOO MANY GCCs? (2)
effect from TOO FEW GCCs? (1)

Answer 11

what does it do?
= BIND INTRACELLULAR RECEPTOR and promote DNA transcription leading to ENZYME SYNTHESIS that ALTERS CELL FUNCTION

effect on other hormones?
–> Has a PERMISSIVE EFFECT on other hormones (catecholamines, glucagon, erythropoietin)

TOO MANY GCCs?
1. GI ULCERATION
2. POLYCYTHEMIA

TOO FEW GCCs = ANEMIA

Question 12

dopamine…
1 main effect?
3 things it increases?

Answer 12

1 main effect? = Renal vasodilation with VASOCONSTRICTION EVERYWHERE ELSE

increases…
1. Systolic BP
2. Force of cardiac contraction
3. Natriuresis

Question 13

ACTIONS of glucocorticoids…
INCREASES? (8)
DECREASES? (2)
INHIBITS? (1)
what HEMATOLOGIC pattern should we expect?

Answer 13

INCREASES…
1. Protein catabolism (proteins –> amino acids)
2. Hepatic uptake of amino acids
3. Gluconeogenesis by the liver
4. Glycogenesis by the liver via increased FORMATION of ACTIVE FORM glycogen synthase
5. Blood glucose concentration
6. Plasma free fatty acids (from breaking down fat)
7. Lipids & ketosis in DIABETICS
8. Glomerular filtration rate

DECREASES…
1. Peripheral glucose utilization
2. Hepatic lipogenesis –> NOT storing fat in the liver

INHIBITS…
1. ACTH secretion

HEMATOLOGY?
= STRESS LEUKOGRAM

Question 14

mineralocorticoids…
function?
increases?
what happens in ADDISON’S? (1 main thing, and 2 causes)

Answer 14

function?
= Binds INTRACELLULAR RECEPTOR and promotes DNA transcription leading to SYNTHESIS OF Na and K CHANNELS/PUMPS

increases?
1. activity of EXISTING Na/K pumps
2. Na reabsorption from BODILY FLUIDS
3. RENAL SECRETION of K and H

addison’s?
1. addison’s = no aldosterone

this then causes…
1. Na to be LOST in the urine
2. K and H+ to be RETAINED to become HYPERKALEMIC/ACIDOTIC

Question 15

true/false check
Glucocorticoids are essential for life
Catecholamines are essential for life
Cortisol suppresses ACTH secretion from the anterior pituitary
Cortisol stimulates CRH secretion from the hypothalamus
Aldosterone, a mineralocorticoid, increases Na+ retention and secretion of K+ and H+
Catecholamines are anabolic

Answer 15

Glucocorticoids are essential for life = TRUE
Catecholamines are essential for life = FALSE
Cortisol suppresses ACTH secretion from the anterior pituitary = TRUE
Cortisol stimulates CRH secretion from the hypothalamus = FALSE
Aldosterone, a mineralocorticoid, increases Na+ retention and secretion of K+ and H+ = TRUE
Catecholamines are anabolic = FALSE

Question 16

REGULATION of catecholamines? (3)

Answer 16

1. Naturally decreases during sleep
2. INCREASES in emergency situations (hypoglycemia, hypothermia)
3. NE has negative feedback system!

Question 17

REGULATION of glucocorticoids?
depends on…
2 options?

Answer 17

depends on…
WHERE ACTH is being secreted from (anterior or intermediate pituitary)
1. In ANTERIOR = regulated by CORTISOL, goes back to pituitary and INHIBITS ACTH
2. In INTERMEDIATE = regulated by DOPAMINE, goes back to pituitary and INHIBITS ACTH

Question 18

normal NEGATIVE FEEDBACK regulation in MINERALOCORTICOIDS? (5)

Answer 18

1. aldosterone is made from the adrenal cortex and helps DECREASE Na/WATER EXCRETION (retains sodium)
2. this therefore INCREASES EXTRACELLULAR FLUID VOLUME and INCREASES BP
3. Increased BP has negative feedback effect on KIDNEY so LESS RENIN MADE
4. LESS RENIN from kidney causes LESS CONVERSION OF ANGIOTENSIN I –> II
5. LESS STIMULATION of angiotensin II to MAKE ALDOSTERONE

Question 19

main 4 adrenal diseases in small animals?

Answer 19

1. Hyperadrenocorticism
2. PRIMARY hyperaldosteronism
3. Hypoadrenocorticism
4. Pheochromocytoma

Question 20

3 most common forms of hyperadrenocorticism?
which one is MOST common? **
why is it important to identify which one it is?

Answer 20

3 most common forms?
1. PITUITARY-DEPENDENT HYPERADRENOCORTICISM (PDH)**
2. ADRENAL TUMOR (AT)
3. IATROGENIC

why is it important?
= because each classification can resemble each other clinically but TREATMENT MODALITIES DIFFER!

Question 21

PITUITARY-dependent hyperadrenocorticism (PDH)..
what causes it?
2 possible locations of the disease/what they do there? (** include which is more common)
prevalence? (2)

Answer 21

what causes it?
1. likely due to PRIMARY DEFECT, often a TUMOR, in PITUITARY that causes excess secretion of ACTH

2 locations?
1. ** Often in ANTERIOR pituitary in dogs, regulated by CRH which provides negative feedback inhibition on GCC production
2. SOME dogs have lesions in INTERMEDIATE pituitary, regulated by DOPAMINE, which inhibits ACTH secretion

prevalence?
1. PDH MORE COMMON THAN AT
2. Most of the time due to PITUITARY ADENOMA in the ANTERIOR pituitary lobe that’s a MICROADENOMA (<1 cm diameter)

Question 22

ADRENAL TUMOR hyperadrenocorticism
prevalence?
how it manifests?
pathophysiology?
2 results of disease process?

Answer 22

prevalence? = LESS COMMON THAN PDH CUSHING’S

manifestation? = ~50% of the time, adrenal tumors are ADRENAL ADENOMAS or ADRENAL CARCINOMAS

pathophysiology?
1. Adrenal adenomas/carcinomas secrete excess GCCs that suppress CRH and ACTH
2. ADRENAL CORTEX NO LONGER STIMULATED

results in…
1. ATROPHY OF CONTRALATERAL GLAND
2. ATROPHY of the zona RETICULARIS & FASCICULATA in the ADRENAL CORTEX of the GLAND w/ the TUMOR

Question 23

SIGNALMENT for cushing’s…
age?
sex?
breeds? (4, 3 breeds + 1 point)

Answer 23

age? = OLDER dogs (~10-11 years)
sex? = FEMALES are at HIGHER RISK
breeds?
1. Standard Shnauzer
2. Dachshund
3. Irish setter
4. Might have genetic factor that contributes to disease, but not a huge contributor because many breeds predisposed

Question 24

true/false questions
Polyuria and polydipsia in Cushing’s develop because glucocorticoids prevent ADH from binding the ADH receptor

Dogs with Cushing’s disease usually have a normal body condition score and nice hair coat

Dogs with Cushing’s disease can have panting due to break down of intercostal muscles, hepatomegaly, and truncal obesity

Answer 24

Polyuria and polydipsia in Cushing’s develop because glucocorticoids prevent ADH from binding the ADH receptor = TRUE

Dogs with Cushing’s disease usually have a normal body condition score and nice hair coat = FALSE

Dogs with Cushing’s disease can have panting due to break down of intercostal muscles, hepatomegaly, and truncal obesity = TRUE

Question 25

CLINICAL SIGNS for Cushing’s? (LONG LIST, 13)
reason word bank:
hepatomegaly
ADH receptor
hunger
obesity
weakness
stiffness
immunosuppression

Answer 25

1. PU/PD** HALLMARK OF CUSHING’S! But NOT ALWAYS present
   –> GCCs bind to ADH receptor and prevents ADH from binding –> no anti-diuretic effect –> polyuria –> compensatory polydipsia
2. Polyphagia (extreme hunger)
3. Abdominal enlargement
   –> Often from BIG LIVER = glycogen accumulates in hepatocytes and liver will SWELL
4. Truncal obesity (fat distribution centered on trunk)
5. Muscle weakness/lethargy/possible lameness
   –> From PROTEIN CATABOLISM
6. Panting
   –> From PROTEIN CATABOLISM of INTERCOSTAL MUSCLES so CANNOT EXPAND RIBS TO BREATHE
   –> Or LIVER GETS SO BIG that it interferes with breathing
7. Thin skin
   –> GCCs on skin cause cutaneous atrophy
8. Pyoderma
   –> GCCs are immunosuppressive
9. Bruising, dehiscence of healing lesions
10. **Calcinosis cutis = PATHOGNOMONIC FOR CUSHING’S
11. Recurrent infections
12. Testicular atrophy/failure to cycle
    –> GCCs suppress LH/FSH secretion
13. Myotonia
    –> STIFFNESS of limbs, usually hind

Question 26

what clinical sign is PATHOGNOMONIC for Cushing’s?

Answer 26

CALCINOSIS CUTIS

Question 27

how can CUSHING’S cause CALCIUM OXALATE stones to form? (2)

Answer 27

1. if animal has CALCINOSIS CUTIS secondary to CUSHING’S!
2. Can cause EXCESS SECRETION OF Ca into URINE and FORMATION OF STONES

Question 28

DIFFERENTIALS for PU/PD? (13)

word bank:
BUN production
diabetes
thyroid
ADH
potassium
calcium

Answer 28

1. CUSHING’S!
2. RENAL disease…
   –> TUBULAR disease = tubules are not concentrating urine
   –> GLOMERULAR disease = PORES in the glomerulus are TOO ENLARGED or LOSE POSITIVE CHARGE
3. LIVER disease…
   –> Inadequate BUN production in liver = less efficient urine concentration by renal tubules
4. DIABETES MELLITUS
   –> Causes EXCESS GLUCOSE IN BLOOD
   –> Glucose also SPILLS INTO URINE and acts as an OSMOTIC AGENT –> PU/PD
5. DIABETES INSIPIDUS
   –> ADH NOT PRODUCED, OR….
   –> NEPHROGENIC/PERIPHERAL diabetes insipidus
6. HYPERTHYROIDISM
   –> Causes INCREASED THYROID CONCENTRATION –> increased BLOODFLOW –> increased GFR to kidney –> POLYURIA
7. HYPOADRENOCORTICISM
   –> From lack of aldosterone so sodium/water NOT BEING RETAINED (increased secretion)
8. HYPERCALCEMIA
   –> Ca prevents ADH from having effect by binding to its receptors, DIURESIS
9. HYPOKALEMIA
   –> K NEEDED for URINE CONCENTRATION via TUBULES
10. DRUGS/IATROGENIC
    –> From GCCs, diuretics, anticonvulsants or fluid overload
11. PYOMETRA
    –> E. COLI can go back to RENAL tubules & have toxic effects
12. PSYCHOGENIC
13. POLYCYTHEMIA

Question 29

how can CUSHING’S cause PULMONARY THROMBOEMBOLISMS? (3)

Answer 29

1. Dogs with Cushing’s are HYPO-COAGULYTIC, meaning that there’s TOO MUCH OF A PLASMINOGEN INHIBITOR
2. This causes the body LESS ABLE TO DEGRADE FIBRIN/UNABLE TO BREAK DOWN CLOTS
3. If clots form, PULMONARY THROMBOEMBOLISMS can be FATAL

Question 30

true/false?

Polyuria and polydipsia in Cushing’s develop because glucocorticoids prevent ADH from binding the ADH receptor

Dogs with Cushing’s disease usually have a normal body condition score and nice hair coat

Dogs with Cushing’s disease can have panting due to break down of intercostal muscles, hepatomegaly, and truncal obesity

Answer 30

Polyuria and polydipsia in Cushing’s develop because glucocorticoids prevent ADH from binding the ADH receptor = TRUE

Dogs with Cushing’s disease usually have a normal body condition score and nice hair coat = FALSE

Dogs with Cushing’s disease can have panting due to break down of intercostal muscles, hepatomegaly, and truncal obesity = TRUE