Histology Of The Endocrine System

Question 1

Pituitary adenomas

Answer 1

Often produce excess numbers of functional acidophils or basophils

If an adenoma involves somatotropin cells = gigantism in children or acromegaly in adults
Due to excessive GH production

Acromegaly Symptoms

• large beefy tongue
• deep voice
• large hands/feet
• coarse facial features with premature aging lines
• diaphoresis
• early insulin resistance and hypertension
• increased risk for colorectal cancers

Diagnosis =increased serum IGF-1, and failure to suppress serum GH levels following oral glucose test
- also pituitary mass is usually seen on MRI

Treatment:

• resection of tumor
• treat with octeotide/pegvisomant or dopamine agonists

Question 2

Diabetes insipidus

Answer 2

Central DI = Caused by any damage to the posterior pituitary

• most common = tumors or head trauma
• always shows decreased ADH
• urine becomes concentrated with ADH shots
• treatment = desmopressin and hydration

Nephrogenic DI = hereditary, secondary to hypercalcemia/hypokalemia or lithium use

• ADH can be lowered or normal
• urine DOESNT become concentrated with ADH shots
• treatment = HCTZ/indomethacin/amiloride/salt restriction

BOTH Result in LOWERED levels of vasopressin which produces:

• inability to concentrate urine which produces chronic clear urine
• polyuria
• polydipsia

Question 3

Addisons disease

Adrenal cortical insufficiency

Answer 3

Any degeneration of the adrenal cortex
- almost always autoimmune based

Results in concomitant loss of glucocorticoids/mineral corticoids and androgens

Question 4

Most common symptom seen in pheochromocytomas

Answer 4

Blood pressure swings hypertension & hypotension

Caused by periodical release of high levels of catecholamines

Question 5

Type 1 and 2 diabetes

Answer 5

Both are characterized by a loss of insulin’s effect of cells being able to uptake glucose from blood stream

Type 1: insulin dependent diabetes

• caused by a loss of B-cells in the pancreas often due to autoimmune dysfunction
• treatment = insulin injects

Type 2: insulin independent diabetes

• caused by B-cells not secreting enough insulin and peripheral target cells being “resistant” to insulin effects
• commonly seen in obesity and other comorbidities.
• treatment is much more difficult and varies from person-person

Question 6

Chronic dietary iodine deficiencies

Answer 6

Chronic deficiency in iodine causes thyroid hormone production to be halted.

This produces thyroid optic cells of the antihero pituitary gland to produce excess TSH in response which leads to hypertrophic thyroid follicles and ultimately enlargement of the overall thyroid gland
- deemed a “goiter”

Question 7

Hyperthyroidism and hypothyroidism

Answer 7

Hyperthyroidism:

• chronic over production of thyroid hormones
• usually induced by Graves’ disease (autoimmune attack on follicular cells in the thyroid which induces over production)
• most common symptoms = weight loss/nervousness/sweating/heat intolerance

Hypothyroidism:

• chronic under production of thyroid hormones
• usually induced by chronic thyroiditis or inadequate secretion of TSH in the anterior pituitary glans
• most common symptoms: tiredness/weight gain/cold intolerance/ inability to concentrate

both are heavily genetic based

Question 8

Hypoparathyroidism and hyperparathyroidism

Answer 8

Hypoparathyroidism

• diminished PTH secretion which casues bones to become MORE DENSE and mineralized
• also causes striated muscles to exhibit abnormal contractions due to inadequate calcium ion concentrations

Hyperparathyroidism

• excessive PTH production LESS DENSE bones and stimulates osteoclast number and activity.
• leads to increased levels of blood calcium which can pathologically deposit into arteries and kidneys and other organs

Question 9

What are corpora arenacea?

Answer 9

Variously sized concentrations of calcium and magnesium salts in the pineal gland

• often deemed “brain sand”
• overall amount increases overtime but serves no known function on the pineal gland

Is often used as a landmark for the midline of the pineal gland

Question 10

Pituitary gland location

Answer 10

Located within the sella turcica of the sphenoid bone

Question 11

Blood supply of the posterior pituitary gland (neurohypophysis)

Answer 11

Two branches of the internal carotid artery

1) inferior hypophyseal artery:
- gives rise to the inferior hypophyseal plexus
- supplies the neurohypophysis
- receives ADH and oxytocin and transports these hormones

2) superior hypophyseal artery:
- gives rise to the hypothalamic-hypophyseal portal system
- primary plexus supplies = pars tuberalis and median eminence
- secondary plexus supplies = pars distal is and intermedia. Receives products from the hypothalamus to regulate blood flow

Question 12

3 parts of the adenohypophysis

Answer 12

1) pars tuberalis
- wraps around the infundibulum stalk and is composed of basophilic gonadotrophs

2) pars intermedia
- adjacent to the pars nervosa and is composed of basophilic corticotrophs/chromophobes/small colloid cysts

3) Pars distalis
- largest component of the adenohypophysis and is the primary functional component
- contains all the hormone secreting cells of the anterior pituitary

Question 13

Embroyonic origin of the anterior vs posterior pituitary

Answer 13

Neurohypophysis:

• arises as part of the ventral diencephalon
• doesnt actually secrete anything and just contains hypothalamus neurons/projections
• does store ADH and oxytocin however that are produced by cell bodies in paraventricular and supraoptic nuclei of the hypothalamus
• primary cells found physically inside the neurohypophysis is pituicytes which is similar to glial cells of the CNS
• is neural ectoderm derived

Adenophysis

• arises from the invagination of mucosa in the superior surface of the oral cavity via ralthes pouch
• contains all hormone secreting cells which are also ectoderm derived
• also contains mesoderm CT
• is oral ectoderm derived from Rathke’s pouch

Question 14

Chromophobes

Answer 14

Heterogenous group of early staining cells with almost no secretory granules.
- found in the adenohypophysis

Induces:

• stem cells
• progenitor cells

Question 15

Acidophillic chromophobes

Answer 15

Identified by pink staining cytoplasmic granules and include two subtypes. Found in the adenohypophysis

1) somatotrophs
- MOST abundant cell type in the anterior pituitary (50%)
- secretes somatotropin (Growth hormone) which acts on all body tissues to stimulate growth

2) Lactotrophs
- secretes prolactin
- acts on mammary glands to promote maturation of secretory glands in breasts

Question 16

Basophilic chromophils

Answer 16

Identified by blue/purple stains cytoplasmic granules. Found in the adenohypophysis.

Three subtypes exist

1) thyrotrophs
- LEAST abundant cell type
- secretes thyroid stimulating hormone (TSH) which stimulates thyroid hormone release from thyroid

2) corticotrophs
- synthesis protein pro-opiomelanocortin (POMC).
- POMC is cleaved into both adrenocorticotropic hormone (ACTH) and B-lipotropin (B-LPH) which function to stimulate the adrenal cortex release of corticosteroids and promotes lipid metabolism respectively

3) gonadotrophs
- secretes both FSH and LH
- FSH = promotes ovarian follicle development and estrogen secretion in females; stimulates spermatogenesis in males
- LH = promotes ovarian follicle maturation and progesterone in females; promotes androgen secretion in interstitial cells in males

Question 17

What are the 4 main “releasing”hormones

Answer 17

All act to promote release of other hormones

1) thyrotropin-releasing hormone (TRH)
2) Gonadotropin-releasing hormone (GnRH)
3) Corticotropin-releasing hormone (CRH)
4) Growth hormone-releasing hormone (GHRH)

Question 18

What are the 2 main “inhibiting” hormones

Answer 18

1) somatostatin
- inhibits release of GH and TSH

2) dopamine
- inhibits release of prolactin

Question 19

What is the most common type of feedback in endocrine system?

Answer 19

Negative feedback

Question 20

Pars nervosa

Answer 20

Terminal portions of axons that form dilation called neurosecretory (herring) bodies
- function is to store accumulated hormone products in membrane bound granules (stains eosinophilic)

Is part of the neurohypophysis

Question 21

Secretory productions and function of the neurohypophysis

Answer 21

Antidiuretic hormone (ADH)

• also known as vasopressin
• is produced by cell bodies in the supraoptic nucleus
• regulation is based on blood toxicity measured by the osmoreceptors in hypothalamus. High toxicity = stimulates release; low toxicity = inhibits release.
• functions to increase water permeability and reabsorption by acting on principle cells in the CD of nephrons

Oxytocin

• is produced by cell bodies in the paraventricular nucleus
• regulation is based on cervical contractions or nursing stimuli
• during child birth = promotes uterine contraction in smooth muscle myocytes of the myometrium (also acts in a positive feedback mechanism)
• during lactation = acts on contractile myoepithelial cells of mammillary glands to stimulate milk production
• **also has a rather noval effect on psychology and behaviors (especially positive physical contact)

Question 22

Three arterial branches that supply the adrenal gland

Answer 22

1) inferior suprarenal artery
- comes off left/right renal artery

2) middle suprerenal artery
- direct branch from abdominal aorta

3) superior suprerenal arteries
- branches off the left/right inferior phrenic arteries

these three arteries form a subcapsular plexus once inside the adrenal glands

venous blood supply leaves via micro vasculature of the medulla through the suprarenal veins

Question 23

Adult adrenal cortex

Answer 23

Is derived primarily from mesoderm derived mesothelium

Differentiate Into cords of steroid-producing epithelial cells that contain enzymes for

• 1) cholesterol synthesis
• 2) conversion of steroid pro hormone pregnenlone into cell-specific active steroid hormones
• also contains mitochondria which can help convert cholesterol in pregnenolone

Contains three distinct layers
- “GFR” and secretes (aldosterone, cortisol and sex hormones respectively)

Question 24

Three zones of the adrenal cortex

Answer 24

1) zona glomerulosa
- most superficial And make sup 15% of cortical tissue
- contains pyramid cells that are medium stained. arranged in rounded/arched cords with a rich capillary network
- secretes aldosterone and mineral corticoids. upregulate salt reabsorption in DCT and CD and control Na/K+ and H20 levels in renal cells respectively
- is controlled/regulated by the RAAS primarily. Can also be regulated by plasma K+ concentration increase or by levels of ACTH in blood

2) zona fasciculata
- middle layer and makes up 65% of the cortical tissues
- contains polyhedral cells with very light staining and numerous lipid droplets. Are arranged in cords 1/2 cells thick and separated by sinusoidal capillaries
- secretes steroid glucocorticoids and cortisol. Stimulates gluconeogenesis and glycogen synthesis in hepatocytes (glucocorticoids)
- suppresses various immune functions and promote fat mobilization and muscle proteolysis (cortisol)
- is regulated by ACTH levels

3) Zona reticularis
- is the innermost layer and makes up about 10% of the cortex
- made up of small dark staining cells with few lipid droplets. Large amount of lipomas in granules though and are arranged in irregular cords with various cell widths.
- secretes weak androgens (such as DHEA) that are converted into testosterone in the peripheral tissues. Also secretes some cortisol but not as much as fasciculata.
- is regulated by ACTH and androgen levels in blood

Question 25

Adrenal medulla

Answer 25

Is made up of chromaffin cells which are neural crest derived - is also analogous to the sympathetic ganglion and are considered to be modified post-ganglion in sympathetic neurons Histology = large polyhedral cells with a Ovale staining cytoplasm and electron dense granules - are arranged in cords/clumps with profuse supply of sinusoidal capillaries Secretes epinephrine and norepinephrine primarily - epinephrine = acts to increase heart rate, bronchodilation and vasodilation for vessels that supply cardiac and skeletal muscles - Norepinephrine = acts as vasoconstrictor for vessels that supply digestive system and skin * *both also stimulate glycogen breakdown in liver and elevate blood glucose levels** Is regulated by sympathetic influence by the CNS - more sympathetic stimulation = more action - less sympathetic stimulation = less action

Question 26

Pancreatic islets of langerhans

Answer 26

Compact spherical or ovoid clusters of endoderm derived endocrine cells embedded among the acinar exocrine tissue of the pancreas There is approximately 1 million of these in the pancreas (majority is found in the tail) Are also relatively pale-staining and separated from acinar tissues by a thin capsule of reticular CT and fenestrated capillaries Contains 5 different specific cells

Question 27

Alpha (A) cells of the pancreas

Answer 27

Makes up 20% of the islet cells and are usually located along the periphery of the islet Functions to secrete glucagon which is used to stimulate glycogenolysis and lipolysis - results in an increase in blood glucose levels

Question 28

Beta (B) cells of the pancreas

Answer 28

Makes up 70% of the islet cells (most common) - are usually located along the periphery of the islet Function is to secrete insulin which acts on various tissues to promote glucose intake by cells - results in a decrease in blood glucose

Question 29

Delta (D) cells of the pancreas

Answer 29

Make up 5-10% of islet cells and are scattered through the islet Functions to secrete somatostatin (growth hormone-inhibiting hormone) - is a paracrine hormone which acts to inhibit secretion of other islet cells as well as inhibts GH/TSH release by the adenohypophysis - * also inhibits HCL secretion by parietal cells of the gastric pits

Question 30

PP cells of the pancreas

Answer 30

Super rare (<1%) of the pancreatic cells and are usually found in the head of the pancreas Function is to secrete pancreatic polypeptide which stimulates gastric chief cell function (release of pepsin) - also inhibits bile secretion and pancreatic acinar secretions (primarily bicarbonate) - *also lowers intestinal motility

Question 31

Enterochromaffin cells (EC)

Answer 31

Super rare (<1%) of pancreas cells and is scattered throughout the pancreas Function is to secrete serotonin

Question 32

Regulation of the pancreas

Answer 32

1) activity of alpha and beta cells = blood glucose levels - >70 mg/dL = stimulation of B; inhibition of A - <70 mg/dL = stimulation of A; inhibition of B 2) somatostatin regulates all other hormones also via paracrine stimulation, - somatostatin is inhibited bu high glucose levels 3) parasympathetics increase both insulin and glucagon 4) sympathetics can increase glucagon but inhibits insulin 5) circulating Norepinephrine directly inhibits insulin based on concentration

Question 33

Diffuse Neruoendocrine system (DNES)

Answer 33

Collection of small neuroendocrine cells scattered throughout tissues of many organs and glands - especially the mucosa of the GI/respiratory tract and pancreatic islets/ducts. Possess a wide variety of endocrine and paracrine functions Consists of three main cells

Question 34

Enterochromaffin cells

Answer 34

DNES cells that stain via chromium salts Are found scattered throughout the GI tract and pancreatic islets and ducts

Question 35

Argentaffin cells

Answer 35

DNES cells that stain with silver nitrate Are found throughout the GI tract

Question 36

APUD cells

Answer 36

DNES cells that demonstrate Amine Precursor Uptake and Decarboxylation activities Produce Serotonin and amine derivatives and are scattered throughout body

Question 37

Thyroid gland facts

Answer 37

Consists of two lobes that lie just anterior-lateral to the trachea Blood supply = superior/inferior thyroid arteries and drained by the superior/middle/inferior thyroid veins Parenchyma contains millions of thyroid follicles which are filled with gelatinous/acidophilic colloid. * *is unusual from other endocrine glands in that their final synthesis and storage of inactive products occurs outside the thyrocytes** - is in the follicular lumen where it is then secreted into active form into th blood stream

Question 38

Thyrocytes | Thyroid follicular cells

Answer 38

Endoderm-derived epithelial cells that originate in the posterior developing tongue - they descend into the primitive neck/throat anterior to the larynx and trachea placement Make up the majority of the thyroid follicles Histological: - have a centrally located nucleus and stain eosinophilic - also contain high rER/golgi complexes/lysosomes and phagosomes - apical surface shows numerous microvilli - active = low-columnar shape cells - inactive = squamous shape cells Secretes inactive (T3/triiodothyronine) and active (T4/thyroxine) thyroid hormones - are secreted at basal surface into microvasculature - both increase metabolic activity by increasing number and size of intracellular mitochondria and act on the same intracellular receptors Regulation = TSH levels and thyroid hormone levels - cold temps = increase secretion - hot temps = decrease secretion

Question 39

Difference between T3 and T4

Answer 39

T3 = is 2-10x greater activity but has only 1.5 day half life T4 = lower activity but has 1 week half life

Question 40

Parafollicular cells (C-cells)

Answer 40

Derived from neural crest cells that migrate into follicular epithelium. Can be observed between follicles as a cell or clusters of cells Histology: - larger than thyrocytes and are pale staining. Secretes calcitonin - works to lower circulating calcium levels in blood by decreasing osteoclast activity and inhibiting calcium reabsorption in renal tubules - **NOTE this is less important in calcium regulation that parathyroid levels

Question 41

Baseline understanding of synthesis of thyroid hormone

Answer 41

1) begins by production in thyroglobulin with 140 tyrosyl residues 2) the 140 tyrosyl residues are then secreted into the follicular lumen via exocytosis 3) uptake of iodide from the blood via Na/I symporters is conducted and then transported into he follicular lumen via I/Cl transporters. 4) iodination of tyrosyl residues (thyroglobulin) occurs and produces monoiodotyrosine (MIT) or diiodotyrosine (DIT) based on if 1 or 2 iodine atoms are attached respectively 5) MIT+DIT or DIT+DIT combinations form pre-T3 or T4 respectively 6) endocytosis of iodinated thyroglobulin fuses with lysosomes to degrade inactive Pre-T3/T4 into active 7) activated T3/T4 is secreted via exocytosis at the basolateral domain and enters blood stream

Question 42

Parathyroid glands

Answer 42

4 small ovoid masses located on the posterior aspect of the thyroid gland - is embedded within the CT of the thyroid capsule Inferior two = come from third pharyngeal pouches Superior two = come from fourth pharyngeal pouches Blood supply comes from inferior thyroid arteries Contains principal (chief) cells which are endoderm derived and makes up the majority of the endocrine cells in the parathyroid glands - Histology: small polygonal cells with rounded nuclei and slightly acidophillic but more basophilic staining cytoplasm and irregular granules - function is to secrete PTH which acts to increase blood calcium via three ways - regulation = blood calcium levels (high levels = inhibits secretion of PTH; low levels = promotes secretion) Also contains oxyphil cells which are degenerated principal cells that exhibit low levels of PTH synthesis - are larger in size and are way more acidophilic staining

Question 43

Three major target tissue cells for PTH action

Answer 43

1) stimulates osteoblasts to release osteoclast-stimulating factor - increases bone-resorption from osteoclast - opposite effect of calcitonin 2) stimulates DCT of the renal cortex to increase calcium reabsorption 3) stimulates vitamin D activation in the PCT which increases calcium absorption across epithelium in small intestines

Question 44

Pineal gland | Epiphysis cerebri

Answer 44

Small pine-cone shaped gland that is attached to posterior wall of the third ventricle - is found just superior to the superio colliculi of the midbrain Is neuroectoderm derived and develops originally in the diencephalon - surrounded by pia mater Contains interstital glia cells which are modified astrocytes that support and maintain pinealocyte structures - have very elongated nuclei

Question 45

Pinealocytes

Answer 45

Most prominent and abundant cell type in the pineal gland Histology: irregular euchromatin nuecli and slightly basophilic staining cytoplasm Secretes melatonin into microvasculature - fluctuating levels in blood influence circadian rhythm and activity in tissues (especially hypothalamus and pituitary) Regulation = dark/light based on the activity of the retinohypothalamic tract in the Suprachiasmatic nuclei

Question 46

Which hormones are hydrophilic vs hydrophobic

Answer 46

Hydrophilic = everything but steroids Hydrophobia = steroids