Histology Of The Endocrine System Flashcards
Pituitary adenomas
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
Diabetes insipidus
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
Addisons disease
Adrenal cortical insufficiency
Any degeneration of the adrenal cortex
- almost always autoimmune based
Results in concomitant loss of glucocorticoids/mineral corticoids and androgens
Most common symptom seen in pheochromocytomas
Blood pressure swings hypertension & hypotension
Caused by periodical release of high levels of catecholamines
Type 1 and 2 diabetes
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
Chronic dietary iodine deficiencies
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”
Hyperthyroidism and hypothyroidism
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
Hypoparathyroidism and hyperparathyroidism
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
What are corpora arenacea?
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
Pituitary gland location
Located within the sella turcica of the sphenoid bone
Blood supply of the posterior pituitary gland (neurohypophysis)
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
3 parts of the adenohypophysis
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
Embroyonic origin of the anterior vs posterior pituitary
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
Chromophobes
Heterogenous group of early staining cells with almost no secretory granules.
- found in the adenohypophysis
Induces:
- stem cells
- progenitor cells
Acidophillic chromophobes
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
Basophilic chromophils
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
What are the 4 main “releasing”hormones
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)
What are the 2 main “inhibiting” hormones
1) somatostatin
- inhibits release of GH and TSH
2) dopamine
- inhibits release of prolactin
What is the most common type of feedback in endocrine system?
Negative feedback
Pars nervosa
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
Secretory productions and function of the neurohypophysis
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)
Three arterial branches that supply the adrenal gland
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
Adult adrenal cortex
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)
Three zones of the adrenal cortex
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
Adrenal medulla
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
Pancreatic islets of langerhans
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
Alpha (A) cells of the pancreas
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
Beta (B) cells of the pancreas
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
Delta (D) cells of the pancreas
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
PP cells of the pancreas
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
Enterochromaffin cells (EC)
Super rare (<1%) of pancreas cells and is scattered throughout the pancreas
Function is to secrete serotonin
Regulation of the pancreas
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
Diffuse Neruoendocrine system (DNES)
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
Enterochromaffin cells
DNES cells that stain via chromium salts
Are found scattered throughout the GI tract and pancreatic islets and ducts
Argentaffin cells
DNES cells that stain with silver nitrate
Are found throughout the GI tract
APUD cells
DNES cells that demonstrate Amine Precursor Uptake and Decarboxylation activities
Produce Serotonin and amine derivatives and are scattered throughout body
Thyroid gland facts
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
Thyrocytes
Thyroid follicular cells
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
Difference between T3 and T4
T3 = is 2-10x greater activity but has only 1.5 day half life
T4 = lower activity but has 1 week half life
Parafollicular cells (C-cells)
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
Baseline understanding of synthesis of thyroid hormone
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
Parathyroid glands
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
Three major target tissue cells for PTH action
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
Pineal gland
Epiphysis cerebri
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
Pinealocytes
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
Which hormones are hydrophilic vs hydrophobic
Hydrophilic = everything but steroids
Hydrophobia = steroids
