Download SSN Histology Thyroid and Pancreas

SSN Histology
Endocrine II
Comments to Patrick McCormick ([email protected])
Thyroid Gland
Basic Structure and Cell Types
1) bilobed endocrine gland
2) comprised of functional units called follicles
a) follicle has a central lumina of colloid
b) follicle is lined by a simple cuboidal follicular epithelium.
i) Follicular cells (99%)
(1) secrete thyroxine (T4) and triiodothyronine (T3)
(2) arise from endoderm.
ii) Parafollicular cells (1%)
(1) secrete calcitonin
(2) arise from migrating neural crest cells
(3) rest on basal lamina, big and blue in bats
3) Adjacent follicles are separated by connective tissue
a) CT contains fenestrated capillaries and lymphatic capillaries.
Function
1) Synthesis of thyroid hormones utilizes thyroglobulin (TG)
a) inactive storage form of thyroid hormones contained within colloid.
2) Iodide actively transported into cells at basal surface via ATP-powered transporter
3) Iodide oxidized to iodine via apical membrane-bound thyroid peroxidase
4) Iodine released to lumen  iodination of TG Tyr chains occurs via thyroid peroxidase
5) On TSH stimulation, follicular epithelial cells collect TG via endocytosis
a) TSH makes follicular epithelial cells more columnar.
6) TG taken up at the apical surface by colloidal resorption droplets
7) migrate to basal surface  fuse with lysosomes  TG degraded to free T4, T3; MIT, DIT
8) T4:T3 released in 20:1 ratio
9) Free T4,T3 enters capillaries
a) binds to thyroxin-binding protein (TBP) (70%), and other protein (25%), 5% free
b) T4  T3 conversion (by 5'-monodeiodinase) occurs in tissues
c) T4  rT3 conversion also occurs; rT3 is physiologically inactive!
10) Negative feedback regulation
a) in anterior pituitary, T4  T3 (by thyroid peroxidase)
b) T3 downregulates TRH receptors on thyrotrophs
Iodothyronine deiodinase enzymes
 All require selenium cofactor
Type I
Type II
Makes plasma T3
Makes local T3
in thyroid, liver, kidney in CNS, anterior pituitary
5' & 5 enz  T3 & rT3
5' enz only  T3
Type III
Inactivates T3 & T4
everywhere
5 enz only  rT3
Hormones
1) T4 or T3
a) T3 is more potent than T4
b) T3 binds to nuclear receptor, stimulates DNA transcription
c) increases BMR, O2 consumption, heat production
i) by increasing Na+/K+ ATPase activity
d) metabolism increases
i) increased glucose absorption from GI tract
ii) potentiates other hormones that affect digestion
iii) catabolic effect  reduced muscle mass
(1) induces syntheses of metabolic enzymes
e) Cardiac Output & Respiratory Rate increase
i) due to increased Heart Rate, Stroke Volume, contractility
ii) up-regulates cardiac β1-adrenergic receptors
iii) increases synthesis of cardiac myosin, sarcoplasmic reticulum Ca2+ ATPase
f) required for growth in young children  ossification & fusion
g) required for CNS development in children
2) Calcitonin
a) lowers blood calcium levels
i) inhibits bone resorption
ii) increases osteoid calcification
b) stimulated by high plasma Ca2+ levels
Regulation
1) Follicular cells
a) low free T3, T4  HT releases TRH  AP releases TSH
b) high free T3, T4  AP stops releasing TSH
c) somatostatin antagonizes TRH
2) Parafollicular cells
a) High plasma Ca2+ levels stimulate secretion, low levels inhibit.
Parathyroid Gland
1) Four small glands on the posterior surface of the thyroid
2) Chief cells
a) more numerous cells
b) small and clear cytoplasm
c) produces parathyroid hormone (PTH)
d) PTH increases Ca2+ levels
i) indirectly increases osteoclast activity  increases bone resorption
ii) increases calcium absorption in small intestine with vitamin D
iii) increases calcium resorption in kidney distal tubule
iv) lowers phosphate resorption in kidney proximal tubule
3) Oxyphil cells
a) numbers increase with age
b) large and acidophilic cytoplasm
c) unknown function
SSN Histology
Endocrine II
Comments to Patrick McCormick ([email protected])
Pancreatic Endocrine
Islets of Langerhans
1) Structure
a) endocrine portion of the pancreas
b) located in the pancreas around capillaries
c) not attached to ducts. (but exocrine is)
d) 1.5% of the cells in the pancreas
e) mostly in the body and tail, not the head.
f) both sympathetic and parasympathetic innervation
i) PS stimulation  promote secretion of insulin & glucagon
ii) Sympathetic stimulation  inhibit secretion of insulin, promote glucagon
2) Alpha cells
a) secrete glucagon in response to:
i) low blood glucose levels
ii) high amino acid levels
iii) sympathetic stimulation
b) glucagon actions:
i) stimulates release of glucose into bloodstream
ii) increases gluconeogenesis (glucose from amino acid metabolites)
(1) to promote GNG, stimulates proteolysis (breakdown of protein, often muscle)
iii) increases glycogenolysis (breakdown of glycogen)
iv) increases lipolysis, stimulates hepatic lipase
c) histology features
i) located on the periphery of the islets
ii) stain red with chrome hematoxylin-phloxine stain (CHP)
iii) stain pale blue with H&E stain
3) Beta cells
a) secrete insulin
i) prepackaged and stored in vesicles in the cytoplasm
ii) stimulus causes release fusion of the vesicles with the plasma membrane
b) secrete insulin in response to:
i) high blood glucose levels
ii) parasympathetic stimulation
iii) enteropancreatic stimulation from stomach and duodenum
(1) explains why sugar by mouth releases more insulin that sugar by injection
c) insulin actions:
i) causes cells to add GLUT4 transporters to plasma membranes
ii) stimulates glycogen and lipid synthesis from glucose
(1) inhibits glycogenolysis and lipolysis
iii) inhibits gluconeogenesis
iv) stimulates glucose oxidation (making energy)
v) increases amino acid uptake  inhibits proteolysis  stimulates protein synthesis
d) histology features:
i) most (75-80%) of beta cells are in the islets
ii) are usually toward the center of an islet
iii) stain blue with CHP (beta=blue)
iv) stain lighter blue than most of the cells in the pancreas with H&E.
(1) other cells in pancreas make enzymes, so they have more RER than islet cells
4) delta cells secrete somatostatin
a) somatostatin inhibits insulin and glucagon secretion
5) protein polypeptide (PP) cells
a) stimulates gastric chief cells, inhibits pancreatic enzymes and GI motility
Example Q:
Slide: Islet of Langerhans, CHP stain, pointer on a blue stained cell.
Which of the following statements is TRUE about the cells at the pointer?
a. the cells secrete glucagon
b. secretion by the cells is responsible for the synthesis of TSH
c. the cells receive no innervation
d. the cells are induced to secrete by an increase in extracellular levels of glucose
e. the secretion of these cells induces the secretion of mineralocorticoids
answer: d