2. Pathology II Flashcards
1
Q
Hyperadrenocorticism (Cushing syndrome) • Chronic exposure to high levels \_\_\_\_ • ACTH-dependent or ACTH-independent • Most cases \_\_\_\_ • Other etiologies – \_\_\_\_ tumor (Cushing disease) – \_\_\_\_-secreting tumors – \_\_\_\_ disease
• Cushing disease causes syndrome, and causes pigmentation; cushing syndrome doesn't always cause \_\_\_\_ • Can get cushing's without altering adrenal gland > giving patient chronic prednisone ○ Iatrogenic is the most common cause • Can get ACTH-dependent or independent ○ Dependent § \_\_\_\_ gland produces ACTH > adrenals at high levels > high steroid ○ Independent § Not pit causing the problem, but something within the \_\_\_\_ gland > a tumor (functional) in the cortex § Iatrogenic • Face becomes big and round ○ Become more \_\_\_\_ • Gaining weight • \_\_\_\_
A
glucocorticoids iatrogenic pituitary steroid genetic
pigmentation
pit
adrenal
edematous
osteoporosis
2
Q
Clinical manifestations
- ____ gain
- Easy bruising
- Moon ____
- Abdominal striae
- ____ weakness
- Fatigue
- ____
- Acne and other infections
- ____ disorders
- Hypertension
- ____
- Irregular menstruation
- ____
- Back pain
- ____ hump
- Erectile dysfunction
- Mucocutaneous ____
A
weight
facies
muscle
osteoporosis
mood diabetes hirsutism buffalo pigmentation
3
Q
• Pigmentation a conseq of cushing ____ not ____
○ Syndrome may be ACTH-indepdnent
§ Pigmentation only occurs in presence of ____ overexpression (and ACTH therefore)
A
DISEASE
SYNDROME
MSH
4
Q
- Treat underlying cause
- Reduce corticosteroid intake
- Block cortisol synthesis
- ____ (Nizoral®)
- Mitotane (Lysodren®)
- ____ (Metapirone®)
- Control cortisol tissue effects
- ____ (Korlym®)
- Bilateral adrenalectomy
- Inoperable pituitary tumor
- Refractory cases• Cushing disease
○ Treat the brain
○ Remove the pathology of the pit
• Cushing syndrome
○ Treat the cause
§ Too much steroids - stop the medication, carefully!
□ If giving patient prednisone for a few weeks > the patients adrenals will shut down entirely > body senses steroids in the system and systemically, the adrenals shut down, when taken off > take them off ____ > need adrenals to readapt decreased steroids in the circulation
® These patients still retain FFF response - and in a stressful situation in a dental office > if taking prednisone and you stop it > may experience an adrenal crisis > body is trying to respond to FFF, but it can’t do it > body crashes
® Pills from 40, 20, 10, 5mg > tapers you down to make sure you don’t experience an adrenal crisis
○ Reduce steroid production from adrenals, or reduce effect of steroids on the downstream tissues > ____ > prevents cortisol (steroid) synthesis from the adrenal gland
§ Used for ____ infections
□ Including patients w ____ disease
® High risk of developing adrenal insufficiency bc of the drugs they’re taking (in addition to protease inhibitors)
○ Drugs that control cortisol on downstream tissues
§ Mifepristone
○ Surgical excision if medication fails > supplement w steroids to maintain normal levels
A
ketoconazole
metyrapone
mifeprestone
slowly
ketoconazole
fungal
HIV
5
Q
Adrenocortical insufficiency (Addison disease)
• Primary
– Destruction or dysfunction of ____
– Only form that induces ____
• Secondary
– Reduced pituitary ____ secretion
• Tertiary
– Reduced ____ secretion
• Important cause of mucocutaneous pigmentation, but not all causes of addisons trigger pigmentation ○ Only addisons caused by \_\_\_\_ pathology to the adrenals cause pigmentation § That's what triggers ACTH to be released from the brain • Can get secondary addisons, or tertiary addisons ○ Secondary addisons > reduced pituitary ACTH secretion § Hypopit > decreased ACTH > not enough steroids produced, and the adrenals are hypo-active § Won't cause \_\_\_\_, bc ACTH is reduced ○ Tertiary § If hypo reduces CRH secretion > less ACTH > less activity from the glands § No \_\_\_\_
A
adrenal cortex
pigmentation
ACTH
hypothalamus CRH
primary
pigmentation
pigmentation
6
Q
Primary adrenocortical insufficiency
• Most often due to autoimmune destruction
– ____
– Anti-21-hydroxylase enzyme
• Infection
– ____
– Fungal
– ____
A
anti-adrenal antibodies
mycobacterial
AIDS
7
Q
Primary adrenocortical insufficiency
• Cancer
• Bilateral adrenal hemorrhage
– Adults – ____
– Children – ____
• Taking warfarin or cumidine > excessive bleeding from the glands ○ In adults • In children > WFS
A
anticoagulant therapy
waterhouse-friderichsen syndrome
8
Q
Adrenocortical insufficiency
ACTH accumulates within blood (____ disease only) Systemic complications
Diffuse mucocutaneous ____
Treat by ____ therapy
A
primary
pigmentation
replacement
9
Q
Cushing disease vs Addison disease
Dexamethasone suppression test
Measures suppression of ACTH secretion from pituitary
1. Measure ____ level in morning
2. 1 mg of ____ at 11 p.m.
3. Measure cortisol following morning
If ACTH not suppressed, then cortisol levels remain ____
ACTH stimulation test 1. Measure cortisol level in morning 2. \_\_\_\_ injection 3. Blood drawn after 60 minutes 4. Measure cortisol Increase in cortisol after stimulation by ACTH then adrenals are \_\_\_\_
• Addison's can be dx via ACTH stim test ○ Makes use of synthetic analog of ACTH ○ First in morning > blood drawn > measure baseline cortisol ○ After blood draw > injected IV w ACTH analog (cosyntropin) > one hour later > blood drawn again > cortisol measured a second time § If adrenals are proper fxn > analog stim should inc cortisol § If doesn't stim cortisol after an hour > glands not fucntioning properly > dx addison's • Cushing disease is tested w the dexamethasone suppression ○ Patient in morning gets blood drawn and cortisol measured ○ Befroe bed > take oral dosage of steroid (dexamethasone) ○ Next morning in lab > blood draw > measure steroid levels § Normal circumstances > big dose of steroid > suppress ACTH and suppress further steroid release from the adrenals § If doesn’t > ACTH const expressed from the pit > indicative of cushing's disease • Usually dex first, ACTH stim second
A
cortisol
dexamethasone
high
cosyntropin
normal
10
Q
Hyperaldosteronism
• Primary (Conn syndrome)
– Usually due to functional ____
• Secondary
– Due to excessive ____ secretion
• Conn ○ Tumor in adrenal that's producing aldosterone § Goes to kidney > complications that arise from aldosterone activity □ Patient will have \_\_\_\_, \_\_\_\_ and \_\_\_\_ (alkalosis) • Secondary ○ Adrenals function properly, except the \_\_\_\_ is not fucntioning properly in the kidney ○ Kidmey insenstive to aldosterone > renin secretion from the kidney > goes to adrenal gland to produce ald > does what it does on the kidney ○ Same result
A
adenoma
renin
HTN
hypokalemia
alkalotic
aldosterone
11
Q
Thyroid gland • \_\_\_\_ neck • Originates from base of \_\_\_\_ • Composed of thyroid follicles – Contain \_\_\_\_ • Hormones and Iodine
• On the backside of the thyroid are the parathyroids • Physically attached at the level of foramen cecum, and then the stalk of tissue is dissolved throughout development ○ IF not > \_\_\_\_ duct cyst • Follicles are lined by \_\_\_\_ epi cells ○ The pink stuff is \_\_\_\_ material § Fluid § Composed of hormones and iodine □ Hormone = \_\_\_\_ (makes up the colloid) • Bt the follicles > parafollicular cells ○ \_\_\_\_ § Directly and completely counteracts action of PTH □ Work on bone and kidney (same structures) • T3 and T4 ○ Produced from thyroglobulin ○ \_\_\_\_ cells (cuboidal) upon stim > convert thyroglobulin to T3 and T4 § Once produced > enter circulation
A
anterior
tongue
colloid
thyroglossal
cuboidal
colloid
thyroglobulin
calcitonin
follicular
12
Q
Thyroid gland • Follicular cells produce – \_\_\_\_ – \_\_\_\_ – \_\_\_\_
• Parafollicular cells produce calcitonin
– Regulates ____ metabolism
– Antagonist to ____
A
thyroglobulin
triiodothyronine (T3)
thyroxine (T4)
calcium
parathyroid hormone
13
Q
Hypothalamus-pituitary-thyroid axis
Hypothalamus > ____
Pituitary > \_\_\_\_ Thyroid > TSH binds to TSH-receptor (TSH-R) > Converts thyroglobulin to \_\_\_\_ - T3 / T4 bound to \_\_\_\_, transthyretin, thyroxine-binding globulin
• Three organs work synergistically, part of the same axis ○ Begins with hypo > produces TRH > acts on the pit to stim TSH > acts on thyroid follicles to trigger conversion thyroglobulin to T3 and T4 ○ TSH binds to TSH receptor on follicular cells > once binds > cascade of events § Most hormones act through G protein receptor > cascade that's mediated via \_\_\_\_ (and \_\_\_\_) (propagates signal into cell)
A
TRH
TSH
T3 and T4
albumin
cAMP
adenylate cyclase
14
Q
• Organs affected by T3/T4 ○ \_\_\_\_ development ○ Brain ○ \_\_\_\_ ○ Skin ○ \_\_\_\_ rate
A
eye
kidney
heart
15
Q
Thyroid diseases • Hyperthyroidism • Hypothyroidism • Developmental • Goiter • Neoplasia
• When hormone levels are out of whack > things go awry • Goiter ○ Enlarged \_\_\_\_ gland ○ \_\_\_\_ of the thyroid manifesting as a diffuse mass of the thyroid • Hypothyroidism ○ Slowing of \_\_\_\_ • Hyperthyroidism ○ Accel of \_\_\_\_ ○ Nervous, agitated
A
thyroid
hyperplasia
metabolism
metabolism
16
Q
Hyperthyroidism • Graves disease due to \_\_\_\_ autoantibodies • Pituitary tumor secreting \_\_\_\_ • Excessive TRH from \_\_\_\_ • Serum thyroid hormones elevated • Plasma TSH elevated or suppressed
• Hyperactivity = hyperthyroidism ○ Most common development > graves disease § \_\_\_\_ disease □ \_\_\_\_ mechanism □ Autoab to TSH receptor on follicular cells > once ab binds to the receptor > overactivates > const activated > whole cascade happens ove r and over again ® Thyroglobulin cont converted to T3 and T4 ○ Tumor § Producing TSH > cont stimulating receptor and producing T3 and T4 ○ Pathology of hypothalamus § Excessive secretion of TRH > pit > high levels of TSH • Treatment pit patholgy diff from graves disease, etc. ○ For a pit tumor > treat w surgery ○ For graves dx > require \_\_\_\_ therapy, or surgery of the thyroid • T3 and T4 are elevated, TSH may be elevated or not ○ Bc of negative feedback mechanism ○ Specifically in context of Grave's dx
A
TSH-R
TSH
hypothalamus
autoimmune
type II
medicinal
17
Q
Graves disease
• Most common cause of hyperthyroidism – \_\_\_\_ with genetic component • \_\_\_\_>>M • \_\_\_\_ thyroid enlargement • Autoantibodies to TSH-R – Thyroid stimulating immunoglobulin – TSH levels \_\_\_\_ • untreated hyperthyroidism may lead to \_\_\_\_
A
multifactorial F symmetric reduced thyroid storm
