USMLE - Endo Part 1

Anatomy and Physiology100 CardsCreated 17 days ago

The thyroid diverticulum originates from the floor of the primitive pharynx and descends into the neck. It remains temporarily connected to the tongue via the thyroglossal duct, which usually involutes but may persist as a pyramidal lobe of the thyroid.

Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?

Thyroid diverticulum arises from floor of primitive pharynx. Descends into neck. Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid

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Key Terms

Term
Definition

Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?

Thyroid diverticulum arises from floor of primitive pharynx. Descends into neck. Connected to tongue by thyroglossal duct, which normally disappear...

Foramen Cecum

Normal remnant of thyroglossal duct in tongue

Most common ectopic thyroid tissue site

Tongue

Presentation of thyroglossal duct cyst

Anterior midline neck mass that moves with swallowing

Presentation of persistent cervical sinus leading to branchial cleft cyst in lateral neck

Small mobile mass on side of neck that does not move with swallowing

What does the Fetal Adrenal Gland consist of?

Outer adult zone and inner active fetal zone

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TermDefinition

Thyroid development
Where does it arise from?
Where does it descend to?
Connected to what by what?

Thyroid diverticulum arises from floor of primitive pharynx. Descends into neck. Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid

Foramen Cecum

Normal remnant of thyroglossal duct in tongue

Most common ectopic thyroid tissue site

Tongue

Presentation of thyroglossal duct cyst

Anterior midline neck mass that moves with swallowing

Presentation of persistent cervical sinus leading to branchial cleft cyst in lateral neck

Small mobile mass on side of neck that does not move with swallowing

What does the Fetal Adrenal Gland consist of?

Outer adult zone and inner active fetal zone

Adult zone of fetal adrenal gland
Activity?
Control of activity?

Dormant during early fetal life but begins to secrete cortisol late in gestation
Fetal pituitary and placenta make ACTH and CRH

What is fetal cortisol responsible for?

Fetal lung maturation and surfactant production

Embryological origin of adrenal cortex?

Mesoderm

Embryological origin of adrenal medulla?

Neural Crest Cells

Layers of Adrenal Gland w/ Secretory Products

“GFR –> Salt, Sugar, Sex
Deeper you go, the sweeter it gets”
Capsule
Zona Glomerulosa –> Aldosterone
Zona Fasciculata –> Cortisol, Sex Hormones
Zona Reticularis –> Sex Hormones (androgens)
Medulla –> Catecholamines (NE, Epi)

Zona Glomerulosa
Responsive to
Secretory Product

Renin-Angiotensin –> Aldosterone

Zona Fasciculata
Responsive to
Secretory Product

ACTH, Hypothalamic CRH –> Cortisol, Sex Hormones

Zona Reticularis
Responsive to
Secretory Product

ACTH, Hypothalamic CRH –> Sex Hormones (androgens)

Adrenal Medulla
Responsive to
Secretory Product

Preganglionic sympathetic fibers –> ACh –> Catecholamines (NE, Epi)

Most common tumor of adrenal medulla in adults?

Pheochromocytoma

Most common tumor of adrenal medulla in children?

Neuroblastoma

Pheochromocytoma vs Neuroblastoma in terms of clinical presentation

P –> episodic HTN

Adrenal gland venous drainage

L Adrenal –> L Adrenal Vein –> L Renal Vein –> IVC
R Adrenal –> R Adrenal Vein –> IVC

Posterior Pituitary Gland

AKA

Products

Source of products?

How are they transported?

Embryological origin

Neurohypophysis
Secretes ADH and Oxytocin made in hypothalamus and shipped to PP via neurophysins (carrier proteins)
Derived from neuroectoderm

Anterior Pituitary Gland
AKA
Secretory Products
Embryological origin

Adenohypophysis
“My FLAT PiG”
Melanotropin (MSH), FSH, LH, ACTH, TSH, Prolactin, GH
Derived from oral ectoderm (Rathke’s Pouch)

Acidophils in the Anterior Pituitary gland secrete

GH and Prolactin

Basophils in the Anterior Pituitary gland secrete

“B FLAT” Basophils –> FSH, LH, ACTH, TSH

Which hormones share the same α subunit?

FSH, LH, TSH, and hCG

Endocrine Pancreas
Name
Cell types: Products and Location
Embryological origin?

Islets of Langerhans

"INsulin is on the INside"

α: Glucagon, Peripheral

β: Insulin, Central

δ: Somatostatin, Interspersed

Pancreatic Buds

Mechanism of Insulin Release

↑ Glucose metabolism --> ↑ ATP --> closing of K channels --> depolarization --> V gated Ca channels open --> insulin secretion

Does insulin cross the placenta?

No

What organs take up glucose independently of insulin?

"BRICK L"

| Brain, RBCs, Intestines, Cornea, Kidney, Liver

GLUT1

Insulin independent in Brain and RBCs

GLUT2

Bidirectional in β cells, liver, kidney, and small intestine

GLUT4

Insulin dependent in adipose tissue and skeletal muscle

Effects of Insulin

Anabolic

↑ G transport into skeletal muscles and adipose tissue

↑ Glycogen synthesis and storage

↑ Triglyceride synthesis and storage

↑ Na retention by kidneys

↑ Protein synthesis in muscles

↑ K uptake by cells

↑ AA uptake by cells

↓ Glucagon release

What triggers an ↑ in insulin release

Hyperglycemia
GH (via insulin resistance)
β2 agonists

What triggers a ↓ in insulin release

Hypoglycemia, Somatostatin, α2 agonists

Insulin Receptor Cellular Pathway

Insulin --> Tyrosine Phosphorylation --> IP3 and RAS/MAP
IP3 --> Glycogen, Lipid, + Protein synthesis and GLUT4 vesicle mobilization
MAP/RAS --> Cell Growth and DNA synthesis

What does the brain use for energy during starvation?

Ketone bodies

What do RBCs use for energy during starvation

RBCs can only use glucose b/c they cannot preform aerobic respiration

Functions of Glucagon

Catabolic

| ↑ Gluconeogenesis, Glycogenolysis, Lipolysis, Ketone production

What is glucagon secreted in response to?

Hypoglycemia

What inhibits glucagon production?

Insulin, Hyperglycemia, Somatostatin

What does TRH do?

TRH --> TSH and Prolactin

What does DA do in the Pituitary gland?

DA --/ prolactin

What does CRH do?

CRH --> ACTH, Melanocyte Stimulating Hormone (MSH), β-endorphin

What does GHRH do?

GHRH --> GH

What does somatostatin do in the Pituitary?

Somatostatin --/ GH and TSH

What does GnRH do?

GnRH --> FSH and LH

What does Prolactin do in the pituitary?

Prolactin --/ GnRH

Prolactin
Source
Function in Breast
Function in Pituitary

Anterior Pituitary Gland
Stimulates milk production in breasts
Prolactin --/ GnRH synthesis and release which leads to an inhibition of ovulation and spermatogenesis

Regulation of Prolactin Secretion

DA from Hypothalamus --/ Prolactin secretion from Anterior Pituitary
Prolactin in turn increases DA synthesis and secretion in the Hypothalamus thereby inhibiting its own secretion
TRH --> Prolactin secretion

Affects of DA agonists on prolactin?

DA agonists (bromocriptine) inhibit prolactin and can be used to treat prolactinoma

What stimulates prolactin secretion?

TRH, DA antagonists (antipsychotics) and Estrogens (OCP, pregnancy)

Growth Hormone
Name
Source
Function and MoA
Pattern of release
Regulation

Somatotropin
Anterior Pituitary Gland
Stimulates linear growth and muscle mass through IGF1/somatomedin secretion
↑ Insulin Resistance (Diabetogenic)
Pulsatile release in response to GHRH
Secretion ↑ during exercise and sleep
Secretion inhibited by glucose and somatostatin

Excess GH in adults vs children

Acromegaly in adults

| Gigantism in children

Desmolase
Regulation
Action

ACTH --> Desmolase
Ketoconazole --/ Desmolase
D turns Cholesterol into Pregnenolone

Path of Aldosterone Synthesis

Pregnenolone --> [3β Hydroxysteroid dehydrogenase] --> Progesterone --> [21 hydroxylase] --> 11 deoxycorticosterone --> [11β hydroxylase] --> corticosterone --> [aldosterone synthase] --> Aldosterone

Path of Cortisol Synthesis

Pregnenolone --> [17α hydroxylase] --> 17 hydroxypregnenolone --> [3β Hydroxysteroid dehydrogenase] --> 17 hydroxyprogesterone --> [21 hydroxylase] --> 11 deoxycortisol --> [11β hydroxylase] --> Cortisol
or…
Pregnenolone --> [3β Hydroxysteroid dehydrogenase] --> Progesterone --> [17α hydroxylase] --> 17 hydroxyprogesterone -->

Path of Testosterone and DHT production

Pregnenolone --> [17α hydroxylase] --> 17 hydroxypregnenolone --> Dehydroepiandrosterone (DHEA) --> [3β Hydroxysteroid dehydrogenase] --> Androstenedione --> Testosterone --> [5α reductase] --> DHT
or…
17 hydroxyprogesterone --> Androstenedione

Synthesis of Peripheral Estrogens

Aromatase turns Androstenedione into Estrone
Aromatase turns Testosterone into Estradiol
Estrone can convert to Estradiol

Deficiencies in Bilateral Adrenal Hyperplasias

17α hydroxylase, 21 hydroxylase, 11β hydroxylase

Why do adrenal enzyme deficiencies lead to hyperplasia

↑ ACTH stimulation because of ↓ cortisol

17α hydroxylase deficiency

Mineralcorticoids

Cortisol

Sex Hormones

Presentation

Male vs Female

Mineralcorticoids ↑
Cortisol ↓
Sex Hormones ↓
HTN, HypoK
Male: ↓ DHT --> pseudohermaphroditism (variable, ambiguous genitalia with undescended testes)
Female: Externally phenotypic female with normal internal sex organs but lack secondary sex characteristics

21 hydroxylase deficiency

Mineralcorticoids

Cortisol

Sex Hormones

Presentation

Mineralcorticoids ↓
Cortisol ↓
Sex Hormones ↑
Hypotension, HyperK, ↑ Renin activity, Volume depletion
Masculinization leading to pseudohermaphroditism in females

11β hydroxylase deficiency

Mineralcorticoids

Cortisol

Sex Hormones

Presentation

Mineralcorticoids:

↓ Aldosterone, ↑ 11-deoxycorticosterone

Cortisol ↓

Sex Hormones ↑

HTN, Masculinization

Cortisol
Source
Function
Regulation

Adrenal Zona Fasciculata

"BBIIG"

Maintains BP

↓ Bone formation

↑ Insulin Resistance

AntiInflammatory/Immunosuppressive

↑ Gluconeogenesis, lipolysis, proteolysis

Inhibits Fibroblasts --> striae

CRH (hypothalamus) --> Anterior Pituitary --> ACTH --> Cortisol production in Zona Fasciculata

How is cortisol transported in the blood?

Corticosteroid binding globulin (CBG)

How does cortisol maintain BP?

Upregulates α1 receptors on arterioles --> ↑ sensitivity to NE and Epi

How is cortisol an anti-inflammatory/immunosuppressive?

--/ production of leukotrienes and prostaglandins
--/ leukocyte adhesion
--/ histamine release
Reduces eosinophils
--/ IL2 production

How does excess cortisol alter CRH, ACTH and Cortisol secretion

Decreases all of them

How does chronic stress affect cortisol secretion?

Stress induces prolonged secretion

PTH
Source
Function

Chief Cells of Parathyroid

↑ Bone resorption of Ca and PO4

↑ Kidney reabsorption of Ca in DCT

↑ Calcitriol production by stimulating kidney 1α Hydroxylase

↓ Reabsorption of PO4 in PCT

Regulation of PTH

↓ Serum Ca --> ↑ PTH
↓ Serum Mg --> ↑ PTH
↓↓ Serum Mg --> ↓ PTH
↑ Vit D --> ↓ PTH

Common causes of ↓ Mg

Diarrhea, Aminoglycosides, Diuretics, EtOH abuse

Number of Parathyroid glands

4 glands

How does PTH affect bone

Stimulate Ca release from bone mineral compartment
Stimulates osteoblastic cells
Stimulates bone resorption via indirect effect of osteoclasts
Enhances bone matrix degradation

Actions of Vit D

↑ Intestinal absorption of Ca and PO4
↑ Release of PO4 from bone matrix
↑ Bone resorption of Ca and PO4

Clinical manifestation of high PTH

↑ serum Ca, ↓ serum PO4, ↑ urine PO4

How does PTH affect osteoblasts and osteoclasts

PTH --> ↑ production of M-CSF and RANK-L in osteoblasts which stimulates osteoclasts

Source of Vit D

D3 from sun exposure in skin
D2 ingested from plants
Both converted to 25-OH in liver and 1,25-(OH)2 in the kidney

Regulation of Vit D

↑ PTH, ↓ [Ca], ↓ PO4 --> ↑ VitD

| ↑ Vit D inhibits its own production

24,25-(OH)2 D3

Inactive form of VitD

VitD deficiency in adults vs children

Children --> rickets

| Adults --> osteomalacia

Calcitonin
Source
Function
Regulation

Parafollicular cells (C cells) of thyroid
↓ bone resorption of Ca
↑ serum Ca --> calcitonin secretion

Normal role of Calcitonin

"CalciTONin TONes down Ca levels"

| Not important in normal Ca homeostasis but when active, opposes PTH

Which hormones use cAMP

"Go Go FLAT ChAMP"

| GHRH, Glucagon, FSH, LH, ACTH, TSH, CRH, Calcitonin, ADH (V2 receptor), MSH, PTH

Which hormones use cGMP

"Vasodilators"

| ANP, NO, EDRF (Endothelial Derived Relaxing Factor)

Which hormones use IP3

"HAG GGOAT"

| Histamine (H1), Angiotensin II, Gastrin, GnRH, Oxytocin, ADH (V1 receptor), TRH

Hormones that use steroid receptors

"VETTT CAP"

| VitD, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone

Hormones that use Intrinsic Tyrosine Kinases

"MAP kinase pathway - Think growth factors"

| Insulin, IGF1, FGF, PDGF, EGF

Hormones that use Receptor-Associated (Non-Receptor) Tyrosine Kinase

JAK/STAT pathway
Think Acidophiles and cytokines - "PIG"
Prolactin, Immunomodulators (cytokines IL2, IL6, IL8, IFN), GH

In men, what are the effects of ↑ sex hormone binding globulin

Lowers free testosterone --> gynecomastia

In women, what are the effects of ↓ sex hormone binding globulin


Raises free testosterone --> hirsutism

In a women, what happens to SHBG during pregnancy?

↑ SHBG

Thyroid Hormone
Formulations
Source

T3 and T4

| Follicles of thyroid. Most T3 is formed in target tissues

Function of Thyroid Hormone

T3 --> 4 Bs
Brain maturation
Bone Growth (synergism with GH)
β adrenergic effects: ↑ β1 receptors in heart --> ↑ CO, HR, SV, and contractility
↑ Basal metabolic rate: ↑ Na/K ATPase activity --> ↑ O2 consumption, RR, body Temp
↑ glycogenolysis, gluconeogenesis, lipolysis

How is TH transported in the blood

| When is it active?

Thyroxine binding globulin binds most T3/T4 in blood

| Only free hormone is active

When does TBG levels change?

↓ TBG in hepatic failure

| ↑ TBG in pregnancy or OCP (estrogen ↑ TBG)

What is the major thyroid product?
What is it converted into?
Where is it converted?
What converts it?

T4

| Converted to T3 in peripheral tissues by 5'-deiodinase

Which thyroid product binds with greater affinity?

T3

Peroxidase in Thyroid

Oxidation and organification of Iodide as well as coupling of MIT and DIT

Propylthiourcil
MoA
Use
Tox

Inhibits Peroxidase and 5'-deiodinase
Hyperthyroidism
Tox: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity