Endocrine System 1: Thyroid, Parathyroid, Adrenal and Pancreas
Learning Objectives: Basic Characteristics of the Endocrine System
1. Define hormone and target cell.
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Hormones act upon a target cell
Interaction of the hormone with specific receptors on or in the target cell elicits a series of
biochemical changes that ultimately result in a change within the target cell
Autocrine regulation
- If the target cell is the cell that secreted the hormone
Paracrine regulation
- If the target cell is a nearby distinct cell type
2. Describe histological features that are common among endocrine organs
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All endocrine glands are highly vascular
- Secretory cells of the endocrine gland commonly abut directly upon a capillary
- The capillaries have fenestrated endothelia that enable rapid entry of the hormone
into the blood stream
Cells in an endocrine gland are either organized into cords (clusters) or follicles
- Cells organized into cords do not line a lumen
o Tend to be rounded and have only a few junctional complexes
o Sometimes called epitheloid
o Ex. anterior pituitary
- Follicles are structures in which a single cell layer surrounds a central lumen
o Ex. thyroid gland
o Organized into a single layer with polarity and junctional complexes
o Keep with the characteristics of a true epithelium
3. Describe how endocrine glands are classified based on their secretory products.
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Endocrine organs can be classified by the type of secretory product they release… 3 types
- Proteins (proteins and polypeptides)
o ex. anterior pituitary ( secreting growth hormone)
o Protein secretors have abundant rough ER, a prominent Golgi Complex, and
variable numbers of storage vesicles ( except the thyroid gland)
- Amines
o Ex. adrenal medulla (secreting epinephrine, a catecholamine)
o Amine secretors resemble the protein secretors, but with much less RER
- Steroids
o Ex. Ovary (secreting estradiol and progesterone)
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Steroid secretors have abundant smooth ER, mitochondria with tubular cristae,
and numerous lipid droplets containing cholesterol (the common steroid
precursor) and/or the final steroid product
Learning Objectives: Thyroid and Parathyroid Glands
1. Describe the general function and histology of the thyroid gland
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The thyroid gland is a bilobed structure ( with a connecting isthmus) located ventral to the
trachea and inferior to the thyroid cartilage.
Its hormone products are T3 (tri-iodothyronine) and T4 (thyroxine or tetra-iodothyronine),
elevate the basal metabolic rate
Composed of thousands of structural units called follicles
- which are hollow balls of cells filled with a protein-riched fluid called “colloid”
o a homogenous substance consisting of large molecules
- Follicles consists of simple epithelium
- The lamina with an underlying thin layer of CT on the basal surface
- Follicles are always in close proximity to a rich capillary network found in the CT.
o Essential for rapid delivery of hormone products from the thyroid gland to the
target cells
- The height of the cells in the follicular epithelium can vary from squamous to tall
columnar
o The taller the epithelium, the higher the activity level
Follicular epithelial cells of the thyroid gland have the typical ultrastructure of protein secretors:
- RER, Golgi, numerous mitochondria, but very limited secretory droplets
- Numerous lysosomes
2. Outline the process of production and secretion of thyroid hormone
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A precursor form of the hormone is released from the apical surface of the follicular cells into
the follicle lumen where it is stored
The precursor is then passed back through the follicular cells where it is processed into an active
hormone
The active hormone is then released from the basal surface of the cells into the interstitial space
and enters the capillaries
The synthesis and storage of the precursor, iodothyroglobulin, occurs in four steps
- In response to TSH, a large glycoprotein, thyroglobulin (660kD), is synthesized in the
rough ER and then glycosylated in the Golgi complex. The thyroglobulin is then
packaged into secretory vesicles and rapidly exocytosed from the apical surface of the
cell into the follicular lumen. The thyroglobulin protein contains about 125 tyrosine
residues
- The cells of the thyroid follicle take up circulating iodide from te blood through an iodide
pump located in their basal cell membranes
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The iodide traverses the cell to the apical surface. As it is released into the follicle it is
oxidized to iodine
- Immediately after release into the lumen, the thyroglobulin becomes iodinated on its
tyrosine residues, and the two molecules condense, forming iodothyroglobulin. The
iodothyroglobulin is stored in the lumen of the follicle. It may be stored there for long
periods of time.
The processing of iodothyroglobulin to active hormones T3 and T4 occurs in four steps
- Upon TSH stimulation, the thyroid cells endocytose iodothyroglobulin from the lumen
and form phagosomes in the apical cytoplasm.
- Then, lysosomes, which have been randomly distributed in the cell, migrate to the apical
cytoplasm where they fuse with the phagosomes, forming secondary lysosomes
- The proteolytic enzymes in the lysosomes cleave the iodothyroglobulin, releasing two
active hormones, T3 and T4.
- The T3 and T4 pass through the basal surface of the cell and into the bloodstream.
When iodothyroglobulin is digested to release T3 and T4, two other inactive products are also
formed, mono- and diiodotyrosine (MIT and DIT). These products do not leave the cell; they are
broken down into iodine and tyrosine, which are reused by the cell.
3. Relate the function of C cells in the thyroid gland
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Second population of cells in the thyroid gland.
They appear clearer than the follicular epithelial cells in histological preparations, so they are
called C cells or parafollicular cells
C cells are often found in small nests, wedged in between the follicular cells and the basal
lamina of the follicle
Somewhat larger than the follicular cells and contain numerous small cytoplasmic granules
containing calcitonin
C cells do not touch the lumen of the follicle
C cells secrete a polypeptide hormone called calcitonin in response to high concentrations of
blood calcium
Calcitonin stimulates osteoblasts and inhibits osteoclasts, leading to increased bone formation
The end result is decrease in the concentration of blood calcium
4. List several clinical consequences of abnormal thyroid function
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Thyroid hormone deficiencies during fetal or early postnatal life lead to a syndrome called
cretinism, which includes defects in CNS development and stunted growth
Hypothyroidism in adults leads to a condition known as myxedema, in which individuals feel
mentally and physically sluggish. They are cold intolerant and have a loss of appetite, but gain
weight.
Hyperthyroidism, or overproduction of hormone, leads to individuals who are sleepless, heat
intolerant, and lose weight despite increased appetite.
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Graves’ disease is an autoimmune disorder, in which antibodies are made to the TSH receptor
that mimic the action of TSH, leading to increased hormone production.
Lack of iodine in the diet or defects in the production of T3 and T4 lead to overstimulation of the
gland by TSH, which in turn leads to an enlarged gland, a condition called goiter.
5. Describe the function of the parathyroid glands
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There are two pairs of parathyroid glands
- They are located on the dorsal surfaces of the thyroid gland
There are two types of cells:
- the chief cells,
o which are the majority of cells and the oxyphil cells
- The oxyphil cells
o are larger than chief cells
o They also increase in number with age
Chief cells have the characteristic ultrastructure of protein-secreting cells
They have relatively little cytoplasm
- The RER is only moderately well developed.
- Mitochondria are plentiful
The chief cells are the source of parathormone
Function of the parathyroid glands is to secrete parathormone in response to low levels of blood
calcium
- Acts on the gut, kidney and bone
- In bone, parathormone inhibits osteoblasts and stimulates osteoclasts, causing a release
of calcium from the bone into the blood.
- In the kidney, parathormone stimulates phosphate excretion and inhibits calcium
excretion, resulting in return of calcium to the blood.
- In the intestine, parathormone stimulates calcium absorption into the blood
- All of these actions of parathormone increase the concentration of blood calcium
6. List several consequences of abnormal parathyroid function.
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Hypoparathyroidism results in too little parathormone being released. This leads to abnormally
low blood calcium, increased excitability of the nervous system, and in severe cases, convulsions
and muscle tetany.
Hyperparathyroidism results in too much parathormone being released. This leads to
abnormally high blood calcium, which can cause fragile bones and calcium deposits in kidney
tubules and blood vessels.
Learning Objectives: Adrenal Gland
1. Describe the functional organization of blood flow through the adrenal gland
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The adrenal glands are situated at the superior poles of the kidneys and are sometimes called
suprarenal glands
They consists of a cortex and medulla
- Structurally and functionally distinct
- The cortex develops from the mesoderm
- Medulla develops from the neuronal crest
- Medulla is similar to sympathetic ganglia, which are also neuronal crest derivatives
There are two sources of blood for the medulla
Several small arteries, called capsular arteries, branch into the connective tissue capsule that
surrounds the gland
- These arteries create a subcapsular arterial plexus
- The subcapsular arteries give rise to:
o Medullary arteries that pass through the cortex to reach the medullary sinusoids
(capillaries)
o Cortical arteries that form capillaries in the cortex called cortical sinusoids.
These cortical sinusoids receive hormones secreted by the adrenal cortex
Blood from the cortical sinusoids is delivered to the medullary sinusoids.
The medulla receives both arterial blood via the medullary arteries and venous blood that is rich
in cortical steroids.
The medullary sinusoids are drained by one or a few veins.
2. Describe the structure and function of the zona glomerulosa
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Outermost
Contains small cells arranged in arched cords
Cells have abundant smooth ER, Golgi, and mitochondria
Cells secrete mineralcorticoids, mainly aldosterone
- Aldosterone is a steroid hormone that primarily targets the kidney, but also targets the
salivary and sweat glands.
- Aldosterone helps maintain water and electrolyte balance by stimulating cells of the
kidney distal convoluted tubule to absorb sodium ions.
The zona glomerulosa cells are under renal control
- When blood pressure is too low, certain cells in the kidney secrete rennin, which
converts circulating angiotensinogen to angiotensin I, which is then converted to
angiotensin II
- Angiotensin II stimulates the release of aldosterone from the zona glomerulosa
- Blood pressure increases when sodium and water are retained
- As sodium is reabsorbed, potassium is excreted through the action of Na+/K+ ATPases
3. Describe the structure and function of the zona fasciculata
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Middle
Cells are large, polyhedral, pale staining cells that are arranged in columns, usually two cells
wide
Running along each column there is a sinusoidal capillary
Cells have the typical characteristics of steroid-producing cells: large lipid droplets, abundant
smooth ER, and mitochondria with tubular cristae.
Cells of the zona fasciculata secrete glucocorticoids including cortisol
- Cortisol regulates carbohydrate and protein metabolisms
- These steroids stimulate anabolic activity in the liver and catabolic activity in adipose
tissue and skeletal muscle
- Fats, sugars, and amino acids that are liberated from adipose and muscle cells are used
by the liver for glycogenesis, gluconeogenesis, and enzyme synthesis
Cortisol is secreted at higher levels when we are under stress
- It facilitates glucose production
- It raised blood pressure and reduces inflammation
- This stress hormone depresses the immune system
The zona fasciculata is under direct control of the pituitary gland (via ACTH), through the
hypothalamo-pituitary action
- It is this interaction that causes emotional stress to involve the adrenal cortex
4. Describe the structure and function of the zona reticularis
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Innermost
Cells are much smaller and more darkly staining than those of the zona fasciculata
Arranged into anatomosing cords that are separated by fenestrated capillaries
Function not well understood but it is known that these cells are the source of weak androgens
- Like dehydroepiandrosterone (DHEA) and androstenedione, that stimulate secondary
sex characteristics
- ACTH from the pituitary gland regulates the zona reticularis
5. Describe the structure and function of the adrenal medulla
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Cells are large, pale staining epitheloid cells, sometimes called chromaffin cells
The adrenal medulla secretes epinephrine (adrenalin) and norepinephrine (noradrenalin)
- Two closely related catecholamines
Secretion from cells of the adrenal medulla is controlled by preganglionic sympathetic neurons
At physiological concentrations, epinephrine increases the heart rate and cardiac output
without significantly increasing blood pressure. It also increases the basal metabolic rate
At physiological concentrations, norephinephrine has little effect on heart rate, cardiac output
or metabolic rate, but increases blood pressure by causing vasoconstriction of the peripheral
arteries
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The two hormones are produced in different cel types that have subtle morphological
and histological differences
The secretory granules are different in size and density, with the norephinephrine
granules being somewhat larger and denser than the epinephrine granules
The flow of blood directly from the cortical sinusoids to the medullary sinusoids means that
cortisol-rich blood supplies the medullary cells
Cortisol stimulates the synthesis of an enzyme that methyates norephinephrine to produce
epinephrine.
- Epinephrine-producing cells reside in regions of the medulla that are fed with blood
drained from the cortex
6. List several consequences of abnormal adrenal function
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Conn’s syndrome
- Occurs when cells of the zona glomerulosa secrete excessive aldosterone.
- This causes high blood pressure and increased potassium excretion from the kidneys
Cushing’s syndrome
- Occurs when cells of the zona fasciculata secrete excessive cortisol
- Fundamental cause for Cushing’s syndrome can be at the level of the adrenal gland
(such as an adrenal gland tumor),l but often it is a secondary consequence of excessive
ACTH secretion from the pituitary gland, often from a pituitary adenoma.
- Symptoms include rapid weight gain, particularly of the trunk and face with sparing of
the limbs, and excessive sweating
Addison’s disease
- Adrenal insufficiency
- Occurs when abnormally low levels of aldosterone and cortisol are secreted from an
adrenal cortex that is damaged by autoimmune disease
- Characterized by weight loss, muscle weakness, fatigue and low blood pressure
Pheochromocytomas
- Tumors of the adrenal medulla which produces excess adrenaline.
- Symptoms include high heart rate, excessive sweating, headaches and anxiety
Learning Objectives Endocrine Pancreas
1. Describe the structure and function of the endocrine pancreas – include the major cell types of the
islets of Langerhans
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The endocrine cells of the pancreas are found in groups scattered throughout the organ and are
known as islets of Langerhans
- May be found as clusters of a few cells to hundreds of cells embedded among the
exocrine acini
- Many fenestrated capillaries lie among the anatomosing cords of cells
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In routinely stained sections, no secretory granules can be identified in the islet cells and
they all look similar
When special staining techniques are used, three cell types can be recognized by the
staining and structure of granules:
o The B or beta cells
 Secrete insulin
 Constitute about 70% of cell population
 Insulin is secreted in response to elevated blood glucose levels
 Principal targets of insulin are the liver, skeletal muscle, and adipose
tissue, where it stimulates uptake of glucose, utilization and storage of
glucose by the cells, and synthesis of glycogen from phosphorylated
glucose
 Insulin lowers blood glucose levels
 In the metabolic disease
o The A or alpha cells
 Secrete glucagon
 Account for ~20% of the islet cells
 Glucagon is secreted by alpha cells in response to low blood glucose
levels
 Glucagon stimulates hepatocytes to break down glycogen into glucose (
glycogenolysis) and to synthesize new glucose ( gluconeogenesis)
 Glucagon elevates blood glucose levels
o The D or delta cells
 Secrete somatostatin
 Comprise about 5% of the islet cells
 Somatostatin was named for its effect on inhibiting secretion of growth
hormone from the pituitary gland
 It suppresses the secretion of both insulin and glucagon in a paracrine
fashion
 Somatostatin also suppresses pancreatic exocrine secretions, by
inhibiting cholecystokinin-stimulated enzyme secretion and secretinstimulated bicarbonate secretion
 Somatostatin is secreted by scattered cells in the GI epithelium, and by
neurons in the enteric nervous system. It has been shown to inhibit
secretion of many of the other GI hormones, including gastrin,
cholecystokinin, secretin and vasoactive intestinal peptide
o The remaining 5% of the islet cells secrete at least 7 different hormones
2. List the consequences of abnormal B(eta) cell function
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In the metabolic disease diabetes mellitus, insulin deficiency leads to elevated blood glucose
levels (hyperglycemia), accompanied by excretion of glucose in the urine (glycosuria)
Endocrine system II The Pituitary Gland
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The pituitary gland controls many of the other endocrine glands, and through its interactions
with the hypothalamus, integrates many of the functions of the nervous and endocrine systems.
It has a central role in controlling homeostasis of the body.
1. Describe the organization of the pituitary gland
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The pituitary gland has two major parts that are structurally and functionally distinct:
The adenohypophysis ( the anterior pituitary)
- Develops as an outgrowth of the oral cavity and is glandular epithelium
- Divided into three regions: the pars distalis, the pars intermedia, and pars tuberalis
- The pars distalis is the major lobe of the adenohypophysis
Neurohypophysis ( the posterior pituitary)
- Develops as an outgrowth of the brain and is neuronal secretory tissue
- Has two parts: the pars nervosa and the infundibulum (funnel)
- The pars nervosa is the major lobe of the neurohypophysis
- The infundibulum is subdivided into two portions: the median eminence and the
infundibular stem
- The median eminence is the upper portion of the infundibulum that connects directly to
the hypothalamus
- The stem is the lower portion of the infundibulum that connects directly to the pars
nervosa
2. Discuss the vascular supply of the pituitary gland and its role in the function of the
adenohypophysis
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Arrangement of vasculature in the pituitary gland is essential for its function
Very little direct supply of arterial blood to the adenohypophysis
Blood entering the adenohypophysis first passes through the infundibulum of the
neurohypophysis
Blood enters the infundibulum from the superior hypophyseal arteries, branches of the internal
carotid arteries
These arteries form a bed of fenestrated capillaries called the primary capillary plexus
The capillaries converge to form the hypophyseal portal veins
The portal veins flow through the pars tuberalis into the pars distalis and form another
fenestrated capillary bed, the secondary capillary plexus
These capillaries converge to form the hypophyseal veins that leave the pituitary gland and
empty into the dural venous sinuses
This vascular network that feeds the pars distalis is called the pituitary portal system
In contrats to the pars distalis, the pars nervosa has a direct vascular supply
Blood enters the pars nervosa via the inferior hypophyseal arteries
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The vessels form a capillary plexus, the capillaries form hypophyseal veins that drain into a
nearby dural venous sinus
3. Relate how groups of neurons in the hypothalamus control the function of the pituitary gland
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The hypothalamus controls both the adenohypophysis and neurohypophysis, but uses different
mechanisms in each case
Adenohypophysis
- Within the hypothalamus there are several distinct nuclei- groups of cell bodies with a
common function
- These neurons’ axon terminals are in the infundibulum
- In response to an input from the CNS and hormones, these neurons release hormones
from their axon terminals into the vicinity of the primary capillary plexus of the
infundibulum
- These releasing ( or inhibiting) hormones/factors are secreted in minute amounts
- There are six different releasing ( or inhibiting hormones)
- The hormones enter the primary capillary bed and are transported to the pars distalis
through the pituitary portal system
- In the adenohypophysis, these hormones exit the secondary capillary bed and act upon
their target cells, either stimulating or inhibiting their secretory activity.
- The pituitary gland is organized so that a specific releasing factor is delivered to its
target cells in the most direct and efficient manner possible
- In the hypothalamus a given nucleus is responsible for producing a specific releasing
hormone
- The axons from that nucleus terminate in a restricted region of the primary capillary
plexus
- The portal vessels in the area deliver it to specific regions in the adenohypophysis where
the appropriate target cells predominate
- There is relatively little mixing of releasing hormones in the blood of the portal vessels
and the releasing hormone is distributed primarily to regions where the corresponding
target cells are most abundant
- Results in high efficiency and quick reaction and facilitates the specify of response
Neurohypophysis
- The pars nervosa is composed primarily of axons that originate in two nuclei of the
hypothalamus: the supraoptic and paraventricular nuclei
- The axons run directly from these nuclei down through the infundibulum into the pars
nervosa where they terminate
- This direct connection of the hypothalamus and pars nervosa is called the
hypothalamohypophyseal tract
- The neurohypophysis is really just an extension of the hypothalamus
4. Describe the basic histology of the adenohypophysis
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Cells in the pars distalis and pars tuberalis are organized into cords of epitheloid cells
surrounded by a small amount of reticular connective tissue
The secondary capillary bed forms an anastomotic network within the connective tissue
Some of the cords contain mostly one cell type, while others contain several types
Most of the cells and therefore most of the secretory activity, of the adenohypophysis are found
in the pars distalis
The pars tuberalis contains some clusters of functionally secretory cells, but the most prominent
histological feature of this lobe is the presence of large pituitary portal veins
In humans the pars intermedia is reduced to a rudimentary structure with no identifiable
secretory product… a few cells may be present
Each cell type in the adenohypophysis is classified as a chromophobe or a chromophil, based
upon its affinity for various stains.
Chromophobes stain very poorly
- Chromophobes are thought to be degranulated chromophils and/or stem cells for
chromophils.
- Chromophils stain strongly
- Chromophils are the cells that actively produce hormone
- Chromophils are fist divided into two classes based upon their staining characteristics
o Acidophils that stain strongly with acidic dyes
 Acidophils are further divided into two distinct cell types:
 Somatotrophs
 Mammotrophs
o Basophils that stain strongly with basic dyes
 Basophils are divided into three cell types:
 Gonadotrophs
 Thyrotrophs
 Corticotrophs
All chromophils in the adenohypophysis have the typical histological features of regulated
protein secretors
Unlike protein secreting epithelial cells in exocrine glands, the cells in the pituitary gland are not
so sharply polarized
The secretory droplets are more generally distributed throughout the cell.
When the cell is stimulated to secrete, the droplets migrate toward the surface closest to a
capillary, where they exit the cell for dissemination through the bloodstream to their target cells
5. List the targets of the functions of the hormones produced in the adenohypophysis
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There are six major protein hormones produced in the adenohypophysis
In general, anterior pituitary hormones secretion is linked to either metabolic regulation ( GH,
ACTH, TSH) or reproduction (FSH, LH, PRL)
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GH
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ACTH
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Thyroid Stimulating Hormone
Stimulates the thyroid gland to produce T3 and T4, which increase the basal metabolic
rate
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Follicle stimulating hormone
In females FSH stimulates the ovary to produce estrogen, which is required for follicular
(oocytes) and uterine growth
In males, FSH stimulates the Sertoli cells of the testes to produce androgen binding
protein, which is necessary for spermatogenesis
FSH
LH
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Adrenocorticotrophic Hormone
Stimulates one part of the adrenal cortex ( the zona fasciculata to produce
glucocorticoids ( primarily cortisol in humans), which affect metabolism and the immune
system
TSH
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Growth hormone ( also called somatotropin, STH) stimulates the liver to produce
somatomedin, which stimulates bone growth and metabolism in most cells
Luteinizing Hormone
In females, LH stimulates ovulation, corpus luteum formation, and progesterone
production
In males LH stimulates the Leydig cells to secrete testosterone, which is required for
spermatogenesis
PRL
- Prolactin or mammotrophin
- PRL stimulates the mammary gland to produce milk
- It appears to stimulate proliferation of oligodendrocytes precursor cells in the CNS
- High prolactin levels in men can be a cause of infertility.
Each cell type in the adenohypophysis is stimulated to secrete a unique protein hormone by a
corresponding releasing hormone from the hypothalamus
- Somatotropin releasing hormone (SRH, or growth hormone releasing hormone, GRH)
stimulates the Somatotrophs to secrete GH ( somatotropin)
- The hypothalamus produces an inhibiting hormone, PIH, which suppresses prolactin
production by the mammotrophs. When PIH secretion is suppressed, prolactin is made
and secreted by the mammotrophs
- TRH stimulates the Thyrotrophs to secrete TSH
- GnRH stimulates the Gonadotrophs to secrete both FSH and LH.
- CRH stimulates the Corticotrophs to secrete ACTH
ACTH is first made as a precursor called proopiomelanocortin (POMC)
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This glycoprotein encodes melanocyte stimulating hormone (MSH), ACTH and betalipotropin (LPH)
Portions of LPH contain the amino acid sequences of the opiate like neural oligopeptides
( endorphins and enkephalins)
6. Describe the basic histology of the neurohypophysis
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When stained with conventional histological dyes, the neurohypophysis looks like a fibrous mass
with a few scattered nuclei and collections of neurosecretory material
The infundibulum consists of unmyelinated axon, blood vessels and glial cells, called pituicytes
that are comparable to astrocytes of the CNS
The pituitary portal veins course along the edges of the infundibulum in the pars tuberalis
The axons contain neurosecretory material that is moving down the axon toward the pars
nervosa
The pars nervosa contains the nerve endings of these unmyelinated axons that originate in the
supraoptic and paraventricular nuclei of the hypothalamus
Clumps of neurosecretory material can be seen in images of these nerve endings within the pars
nervosa where they are concentrated and stored until being released
These concentrations of oxytocin or vasopressin at the nerve terminals are called Herring bodies
7. List the targets and the functions of the hormones produced in the neurohypophysis
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There are two peptide hormones, oxytocin and antidiuretic hormone (ADH, also called
vasopressin) that are stored in and secreted by the neurohypophysis
Hormones are produced by the supraoptic and paraventricular nuclei of the hypothalamus
Most of the oxytocin is produced in the paraventricular nucleus and most of the ADH is
produced in the supraoptic nucleus
The hormones are bound noncovalently to specific transport proteins, neurophysins and ATP
The hormone-transport protein complex travels down the axons through the infundibulum and
into the pars nervosa, where the hormones are stored in the axon terminals until the neurons
are stimulated to release them
Upon stimulation, the axons release the hormones in the surrounding tissue, where they enter
the rich capillary plexus in the pars nervosa
In histological sections aggregates of hormone complexes can be loose clumps of punctuate
material called neurosecretory substance
In the pars nervosa the complexes look like tight clumps of material called Herring bodies
Oxytocin stimulates contraction of the uterine smooth muscle during childbirth and the breast
myoepithelial cells causing milk let down. It is also a neurotransmitter in the brain and may play
a role in the human sexual response
ADH acts on the collecting tubules and ducts of the kidney to increase resorption of water. This
is one of the important ways which the osmotic pressure of the blood is regulated and how
hypertonic urine is produced.
8. Discuss how the endocrine system is regulated by feedback mechanisms
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The endocrine system is tightly regulated by feedback mechanisms
The activities of the hypothalamus and pituitary gland are both directly and indirectly influenced
by the levels of hormones produced by their “target” organs
Ex. Decrease levels of circulating thyroxine leads to increased levels of TRH secretion by the
hypothalamus, which results in increased TSH production by the pituitary gland.
The increased TSH causes increased secretion of thyroxine by the thyroid gland
The elevated levels of circulating thyroxine lead, both directly (via negative feedback on the
pituitary) and indirectly ( via negative feedback on the hypothalamus) to decreased secretion of
TSH by the pituitary gland.
9. List some of the clinical consequences of abnormal pituitary function
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The hypothalamus and pituitary gland play a central role in adjusting the body’s internal
hormonal balance
Overproduction of growth hormone by the Somatotrophs before puberty causes gigantism due
to overgrowth of the long bones, whereas underproduction of growth hormone causes
dwarfism
Overproduction of growth hormone later in life leads to a condition called acromegaly. The
result is enlarged facial, hand, and foot bones.
Lack of ADH release from the pars nervosa causes high volumes of dilute urine to be excreted,
which is characteristic of diabetes insipidus. Over production causes excess fluid retention by
the kidney.
Overproduction of prolactin in men can cause infertility. In women, this condition can lead to
irregular or absence of periods, infertility, and abnormal spontaneous secretion from the breasts
Overproduction of TSH causes hyperthyroidism and underproduction causes hypothyroidism
Overproduction of FSH and LH is rare and do not have any apparent negative effects.
Underproduction of FSH and LH causes infertility
Overproduction of ACTH causes Cushing’s disease. Underproduction causes severe fatigue and
lack of appetite with weight loss.
Specialized Connective Tissue II: Bone
1. List the composition and functions of bone
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Bone provides mechanical support for movement and protect vital structures
Important for housing hematopoietic elements
Stores 98-99% of the body’s calcium, 85% of the body’s phosphorus and 65% of the body’s
sodium and magnesium
o Serves as a metabolic reservoir of mineral salts
Bone is a composite material consisting of inorganic and organic components
Minerals, proteins, water, cells and some other macromolecules including lipids
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The exact composition of bone varies with age and anatomic sites
o Inorganic or mineral phase of bone accounts for 60-70% of the tissue
o Water accounts for 5-8% of the tissue
o Organic matrix makes up the risk
o 90 of the organic matrix is type I collagen and 8% is noncollagenous proteins
o Collagen is the most abundant mammalian protein
o The mineral phase consists of hydroxyapatite
Three different types of bone
o Long bone
 Serve as levers
 Have attachment sites for muscles
 Instrumental in movement
o Flat bones
 Support tissues
 Serve as attachment sites for muscle
 Protects organs
o Small or short bones
 Support tissues
 Serve as attachment sites for muscle
 Protect internal organs
2. Describe the general organization of bone.
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Long bone as an example
The enlarged ends of the bone are called the epiphyses
The shaft is called the diaphysis
The region between the epiphysis and diaphysis is the metaphysic
Long bones have three main sources of blood supply
o The nutrient arteries
o Arteries of the periosteum
o The metaphyseal complex
Nerves enter from the periosteum with the arteries and are found with the blood vessels in the
canal systems
Mature bone has two types of functional organization
The outer surface of the bone is composed of compact or cortical bone
o Very dense layer of tissue
o Low porosity
o Surrounds the marrow cavity
o Has a load bearing function
Trabecular, cancellous or spongy bone
o Within the thick walled cylinder of compact bone
o Composed of a collection of plates and rods
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Have a maximum thickness of approx. 200 microns
The spaces between the struts of the trabeculae make the bone quite porous
The porosity varies from 30-90% depending on the location
The organization of the Trabecular bone into plates and rods creates a distinct
architecture
ideally arranged to maximize strength and minimize weight
the spaces among the trabeculae are continuous and are filled with many cells,
extracellular connective tissue, blood vessels and nerves
contents of the spaces make up the marrow
blood cells develop from the stem cells within bone marrow
other stem cells, known as meschenchymal stem cells, are also found in the bone
marrow
3. List the roles of the four types of bone cells in bone formation, maintenance and breakdown.
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Osteoprogenitor cells
o Stem cells that differentiate into osteoblasts
o Also called mesenchymal stem cells or multipotent marrow stromal cells
Osteoblasts
o Bone-forming cells (builders)
o Secrete the extracellular matrix of bone called osteoid
o Directly cover the bone surface they actively deposit
o Analogous to chondroblasts in cartilage
o When active, osteoblasts are cuboidal to columnar
o When inactive they are squamous
o When osteoblasts surround themselves with bone matrix, they are called osteocytes
o Osteocytes remain trapped in the bone matrix until the bone is remodeled
Osteocytes
o Stellate cells that are surrounded by and maintain the bone matrix
o Maintain many connections with other osteocytes for their nutrient supply
o Most numerous bone cells
o Participate in communicating the mechanical load and strain in the bone to guide
formation and degradation
Osteoclasts
o Bone-destroying cells (recyclers)
o Active when bone is being resorbed ( when blood calcium levels are low or when the
bone is being remodeled)
o Osteoclasts are derived from monocytes
o Multinucleated
o Osteoclasts and chondroclasts only differ by the matrix they are degrading
o Highly mobile cells that respond to hormonal signals
4. Describe the process of intramembranous ossification. List a few bones that develop by this
process.
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Bone development formation is called ossification
Intramembranous ossification is the source of most of the flat bones
Takes place within condensations of mesenchymal tissue
Starts when mesenchymal cells condense to form thickened sheets ( or membranes) of cells and
extracellular matrix
Some of these cells differentiate into Osteoprogenitor cells and then into osteoblasts
The osteoblasts secrete matrix called osteoid, which becomes mineralized and thin strips or
islands of bone form
Growth of the flat bone occurs as layers of osteocytes and matrix form to make a plate
The islands of bone grows in length and meet
When the plate attains a certain thickness, a marrow cavity is created by osteoclasts
Inner and outer bony plates are separated and supported by bony trabeculae
Osteoid, which is secreted by osteoblasts, consists of collagen I, glycosaminoglycans and
proteoglycans
A glycoprotein in osteoid, called osteocalcin, binds calcium
Osteoblasts also accumulate calcium and phosphate ions leading to the deposition of
hydroxyapatite in the process called mineralization of osteoid
5. Describe the process of endochondral ossification. List a few bones that develop by this process.
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Develops by replacement of pre-existing pieces of hyaline cartilage
Most common process of bone formation
Prior to this process, a hyaline cartilage model forms in the embryo
o resembles a small version of the adult bone
In the fetus, the perichondrium surround the center of the cartilage model becomes more
vascularized
Osteoprogenitors differentiate and osteoblasts that form within the perichondrium secrete
osteoid
o which becomes mineralized,
o ultimately forming a bony collar that surrounds what will be the diaphysis
What was perichondrium has now become periosteum
The subjacent chondrocytes as they are cut off from their nutrient supply die and their matrix is
mineralized
An osteogenic bud invades the diaphysis of the forming bone
o It consists of a blood vessel, Osteoprogenitor cells, osteoblasts, and other cells following
chondroclasts
Chondroclasts rapidly degrade channels in the calcified cartilage matrix and the middle of the
cartilage model becomes the primary ossification center
o the first site of bone deposition within the cartilage model
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Osteoblast follow behind the chondroclasts and secrete osteoid on the remaining cartilage
trabeculae
Osteoclasts destroy the initial bony trabeculae, converting the central region of the forming
bone into a marrow cavity
o This cavity eventually fills with reticular CT ( collagen III) and hematopoietic tissue
As the primary ossification center is enlarging the bone is increasing in length and diameter
Vessels invade the epiphyses to form secondary ossification centers
The cartilage intervening between the two ossification centers is called the epiphyseal plate (
growth plate or physis)
6. Describe how bones grow in length
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The original hyaline cartilage model is much smaller than the adult bone, it is necessary for the
developing bone to grow dramatically in length
o This occurs due to interstitial growth of hyaline cartilage within the epiphyseal plate
The epiphyseal plate has four distinguishable zones
o Zone of resting cartilage
 Chondrocytes are small
 Inactive and scattered randomly within the matrix
o Zones of proliferating cartilage
 Proceeding towards the diaphysis
 Cell division and alignment
 Daughter cells are aligned along the longitudinal axis of the developing bone
o Hypertrophying cartilage
 Condrocyte enlargement
o Calcifying cartilage
 the chondrocytes die and their matrix is mineralized
 calcified cartilage is degraded by chondroclasts and bone is deposited onto the
residual cartilage trabeculae in the ossification zone
o The zone of proliferating cartilage and hypertrophying cartilage contribute to the
directional interstitial growth that causes the bone to grow in length
During growth cartilage must proliferate at a rate equal to or faster than its rate of destruction
and replacement by bon e
7. Describe how bones grow in diameter.
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Because bone is dense, calcified matrix it cannot grow interstitially (from within) as cartilage can
Bone grows in width by appositional growth
New bone is added by osteoblasts, layer by later, to the surface of the existing bone
Can occur in both types of bone formation, and on both compact and trabecular bone
It can occur in bone remodeling and fracture healing
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On the most outer surface of bone Osteoprogenitor cells, CT cells, blood vessels and a layer of
dense CT form a protective membrane, called the periosteum
Periosteum is not found on articular surfaces, which are covered with hyaline cartilage to
provide a smooth surface with minimal friction for joint movement
In the marrow, Osteoprogenitor cells, associated with a thin layer of connective tissue form the
endosteum
Endosteum lines the surfaces of both the compact bone and the trabeculae of spongy bone.
In response to growth signals, Osteoprogenitor cells within the periosteum proliferate and
differentiate into osteoblasts
o Initiate appositional growth by secreting matrix from their ventral surfaces that is in
contact with the existing bone
As the osteoblasts secrete more matrix, and as new osteoblasts form, they become enveloped
and buried in the matrix
The new osteocytes maintain contact and form gap junctions with thin cellular processes of
osteocytes that are already buried in the bone matrix and with the processes of the new layer of
osteoblasts on the surface
8. Define canaliculi and filopodia.
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The thin cell processes that connect osteocytes are called filopodia
o Structurally similar to very long microvilli
The small canals within with they lie are called canaliculi
Bone is impermeable to substances
Filopodia mediate contact and communication between the osteoblasts and osteocytes are
important
To ensure survival of the osteocytes that are trapped in the matrix, bone cells use filopodia to
exchange nutrients and waste
Each trapped osteocytes is in direct contact with other osteocytes that were trapped earlier,
later, or at the same time
The osteocytes depend on osteoblasts at the periosteal or endosteal surfaces for their nutrient
supply and waste disposal
Nutrients progressively pass from osteoblasts to deeper osteocytes within the bony matrix, and
waste are transferred in the opposite direction
Once an osteoblast is surrounded by matrix and is an osteocytes, additional appositional growth
requires that a new set of osteoblasts begin adding bone to the surface
A lamella ( layer) is the distance between two rows of osteoblasts/osteocytes
The maximum distance a chain of osteocytes can effectively communicate is a depth of about 10
lamellae.
9. Describe the differences between primary/woven and secondary bone.
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Primary bone is the initial bone produced during ossification
o it is destroyed and replaced by secondary bone
o also called woven bone because of the irregularly arranged collagen fibers within its
matrix
o it is neither mineralized as heavily nor organized as well as the secondary bone
Secondary bone
o also called lamellar bone
o has greater mineralization and more regularly arranged collagen fibers
o much stronger than primary bone
bone gets its strength from the organization of its collagen fibers and calcium salts
collagen fibers within mineralized bone are organized in line with stresses on the bone
as osteoblasts synthesize the matrix they orient the collagen fibers in sequential layers
according to the different stresses
all fibers are parallel to each other within a layer
as the cells orient the next layer, the fibers run perpendicular to the previous layer
there can be many alternating layers of collagen fibers within a single lamella
10. Describe the process of bone remodeling.
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All essential nutrients much reach the deepest osteocytes in order for it to survive
The transfer efficiency of substances breaks down at about 10 lamellae
Given that our blood vessels are at the periosteal and endosteal surfaces, bone can only reach a
thickness of 200-400um
This presents a problem since bones of that thickness are incapable of supporting the weight of
the human body
To increase bone thickness enough to support our weight, we need to find a way to keep the
osteocytes alive in the middle of a thicker cortical bone
New blood vessels must be incorporated into the bone
Incorporating blood vessels into the bone is one of the goals of bone remodeling and is initiated
by osteoclasts
Osteoclasts are derived from monocytes that leave the vasculature and aggregate in regions
that need remodeling
Two to 50 monocytes fuse to form a giant, multinucleated osteoclast that is capable of
destroying components of the matrix
As osteoclasts secrete enzymes that dissolve the bone matrix they create tunnels in the bone
New blood vessels grow into these tunnels
The tunnels and vessels within them enter perpendicular to the long axis of the bone before
branching and running parallel to the longitudinal axis
The perpendicular channels entering the periosteal and endosteal surfaces are Volkmann’s
canals
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Those running parallel to the long axis within the compact bone are Haversian canals
The incorporation of blood vessels allows bone to continue to grow in thickness by supplying the
osteocytes with nutrients
Once the canals are formed, osteoblasts form part of the endosteal ( inner) surfaces of these
tunnels)
Remodeling continues throughout life
Remodeling occurs not only when bone weakens but also when the stresses on bone change
When the stresses change, collagen fibers must be realigned to maximize bone strength
During this remodeling process, the osteoclasts assemble and dig an oversized cylindrical core of
bone along the new lines of stress
Osteoblasts close in this tunnel layer by later by secreting osteoid on the new surface so that
canals are narrowed from the periphery toward the blood vessel
These osteocytes have a concentric appearance around the Haversian canal
11. List the parts of an osteon/Haversian system.
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The Haversian canal and these associated concentric lamellae of osteocytes constitute an
osteon or Haversian system
New Haversian systems require 3 to 4 months to complete
When osteoclasts remodel Haversian systems, they remove some concentric lamellae while
leaving others intact
When the new Haversian system is formed the remnants of the old system are not always
incorporated into the new system
The old lamellae that are left behind are called interstitial lamellae
The osteocytes of interstitial lamellae get their nutrients from other osteocytes in adjacent
Haversian systems with which they maintain filopodial connections
Circumferential lamellae are rows of lamellae around the inner and outer surfaces of long bones
o They resemble growth rings of a tree
o They do not have Haversian canals because their osteocytes are close enough to blood
vessels of the marrow cavity or periosteum to receive nutrients
o Inner circumferential lamellae are those lamellae adjacent to the marrow cavity and
outer circumferential lamellae are just beneath the periosteum
12. Discuss the circulation of blood through a bone.
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The primary blood supply to a bone is an artery that enters the bone marrow from the nutrient
canal before branching into arterioles and capillaries
Some branches supply the cells of the marrow
Others follow the endosteum through Volkmann’s canals to supply the compact bone of the
diaphysis
Those entering the endosteum continue to branch and travel longitudinally within Haversian
systems in the compact bone before leaving through the periosteum
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Epiphyseal and metaphyseal arteries supply the epiphysis and metaphysic
13. Identify the structure and function of Sharpey’s fibers.
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Sharpey’s fibers are the type I collagen fibers of tendons and ligaments that are secreted by
fibroblasts and penetrate the surface of bone
They are identified easily because they are large and run obliquely to those in the bone and
periosteum
o ( which are aligned with the long axis of the bone)
Sharpey’s fibers do not grow into bone
They are trapped and surrounded by the advancing bone ( appositional growth)
14. Describe how bones are repaired after a fracture.
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After a fracture the unsalvageable fragments are resorbed by macrophages
The salvageable fragments are united by a callus that forms from the proliferation of cells in the
periosteum and endosteum
If the fractured bone has not moved and is stabilized by a cast during the healing process, then
there is little or no callus and new bony tissue forms by intramembranous ossification
o this is called primary bone healing
If the fracture site is not immobilized then the callus is composed largely of hyaline cartilage that
subsequently is ossified by endochondral ossification
o This is called secondary bone healing
Clinical union refers to when there is enough stability to resume function
Bone remodeling will continue for months to years after this time before it is complete
15. Discuss the role of bone in calcium metabolism and list two hormones that influence the
osteoblasts, osteocytes, and osteoclasts.
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Calcium is perpetually deposited in bone matrix by osteoblasts and resorbed by osteoclasts to
help maintain a constant blood serum calcium level
Parathormone
o (PTH or parathyroid hormone)
o Stimulates osteoclasts to resorb bone
o Releasing calcium into the blood
Calcitonin
o Decreases osteoclastic activity
o Increases osteoblastic activity
o Reducing blood calcium
Estrogen
o Has a significant effect on calcium deposition in the bone
o Believed to be the result of its ability to antagonize the effects of PTH
16. Describe how osteoporosis and Paget’s disease affect bone
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Bone mass peaks at age 30, stays relatively static until the 5th decade followed by gradual
decline
Men and women lose cortical bone mass at about the same rate
When women go through menopause they have more rapid decline in trabecular bone mass
than men
Osteopenia is neither a precise term nor a disease but rather a generic term used to describe
decrease bone density on x-rays
Bone mineral will be lost in many patients during the course of fracture healing due to limited
weight bearing or muscle use of an extremity
Osteomalacia is a process of deficient or impaired mineralization of bone matrix
o Problem of bone quality, not quantity
o Juvenile counterpart is rickets
Osteoporosis occurs when there is an imbalance in bone resorption and bone formation
o Can occur with either an increase in bone resorption or a decrease in bone formation
o Substantial decline in bone mass
o Bone loss is chiefly seen at the endosteal surface and clinical manifestations of lost
cancellous bone tend to precede those of lost cortical bone
o one current treatment of osteoporosis is oral or intravenous bisphosphonates (
Fosamax, Zometa) which bind to the calcified matrix and kill osteoclasts
o Another treatment is a daily injection of parathyroid hormone (Forteo)
 Parathormone increase serum calcium by stimulating osteoclast activity
 PTH receptors are found largely on osteoblasts, where they stimulate the
expression of factors, such as Receptor activator of nuclear factor kappa B
ligand (RANKL), that then promote osteoclast generation
 Simultaneously, PTH induces the steroid 1 alpha-hydroxylase in kidney to
facilitate generation of the active form of vitamin D (1,25-DHCC)
 Early effects of PTH are actually on osteoblasts, and together with the action of
1,25-DHCC, it can facilitate the proper remodeling of bone
 Long term use of PTH leads to increased osteoclast generation and bone
resorption
Paget’s disease
o bone breaks down more quickly
o when it grows again it is softer than normal bone
o it can affect any bone, but usually affects the skull, the hip and pelvis bones and bones
in the legs and back
o when an area is destroyed in a patient with Paget’s disease, the bone that replaces it is
more porous
o Soft bone can be weak and easily bend, leading to shortening of the affect part of the
body
o The bone replacement also takes place very quickly
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Can cause the bone to get larger and break easily
Bone tends to have more blood vessels than normal, which causes an increase in the
blood supply to the area
Muscle Tissue: Skeletal and Smooth Muscle
1. List the steps of skeletal muscle development and regeneration
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The myotome (myo=muscle, tome= layer) of the somite in the embryo forms skeletal muscle of
the body wall and limbs.
After migrating from the somite ( which forms next to the neural tube), to the appropriate
location, hundreds of myoblasts ( blast=dividing cell) start to fuse with each other tto form a
myotube
o A long, thin multinucleated cell
Once a cell has fused into the myotube, its nucleus can no longer divide
Initially the nuclei are centrally placed and run down the length of the myotube in single file
Between the nuclei, the myotube contains glycogen and many free polysomes for synthesizing
contractile filaments
The contractile proteins assemble into sarcomeres ( sarco=muscle) in a very regular
arrangement
o Giving the muscle a striated appearance
Groups of sarcomeres link together and form cylindrical structures called myofibrils that
gradually fill the myotube and cause it to increase in diameter
o This process is called hypertrophy
o As this process continues, so many contractile filaments accumulate that the nuclei are
displaced to the periphery of the tube
o The tube is then reclassified as a myofibers
Some myoblasts do not fuse with the myofibers during its development
o These reserve cells are called satellite cells
o They are a type of adult stem cell found between the myofibers sarcolemma ( cell
membrane) and its external lamina
Each nucleus in a myofiber can maintain a particular portion of the cytoplasm and contractile
filament
For growth to occur, it is necessary to add more nuclei to the fiber
During postnatal muscle growth, satellite cells divide and fuse with their myofibers to increase
the number of myonuclei
In adult muscle, satellite cells are normally quiescent and only become mitoically active in
muscle injury or disease
Skeletal muscle can regenerate completely following must injuries due to the proliferation and
fusion of satellite cells
2. Describe the organization of myofibers and CT within skeletal muscle
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Easy to see the organization of the contractile proteins ( myosin and actin ) in striated muscle
In longitudinal section, the alternating dark and light bands of the contractile units, called
sarcomeres, give skeletal muscle its striated appearance
Skeletal muscles are made up of hundreds of myofibers aligned in parallel
Cell Shape
o Myofibers are cylinders that vary in length and diameter
o All of the myofiber nuclei are found at the perimeter, just underneath the sarcolemma
o The nuclei have intermediate chromatin density and are shaped like long, slender
rectangles with rounded corners
o The long axes of the nuclei are always parallel with the long axis of the myofiber
Relationship to Connective Tissue
o Skeletal myofibers depend on connective tissues for their nutrition, and for transmitting
the force they generate
o Although the connective tissue investment ( wrapping ) of skeletal myofibers is
described in three layers, you should recognize that the layers form a continuum
because one layer grades smooth and into and attaches to the next
o Endomysium
 Each myofiber is surrounded by its own external lamina
 The reticular lamina component blends into an extremely thin layer of loose
connective tissue, the endomysium ( inner muscle CT)
 Each myofiber has at least one capillary running longitudinally along its surface,
within the endomysium
o Perimysium
 Myofibers are grouped together into fascicles ( groups of 10-50 myofibers) that
are bundled by coarser wrappings of loose connective tissue called Perimysium
(middle muscle CT)
 These divisions provide paths for larger vessels as well as slippage plans so that
fascicles can contract and relax independently of each other
o Epimysium
 The fascicles are bundled together into the named muscles (biceps, pectoralis,
etc.) by dense, irregular connective tissue called the Epimysium ( outer muscle
CT)
o Myotendinous junction
 At the end of each myofiber, the force it generates is transmitted to the tendon
 Tendons are made up of dense, regular connective tissue that transmits the
force generated by the muscle to the bone
3. Discuss how skeletal muscles receive their motor innervations and its impact on fiber type.
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Skeletal myofibers depend upon their innervations to stimulate contraction
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Every mature myofiber has one axon terminating on it in a single neuromuscular junction (NMJ)
When motor axons reach the muscle they innervate
They send branches through the connective tissue layers to reach the individual myofibers
Neuromuscular junctions are located in the endomysium
Whenever two different tissue types adjoin each other, they are separated by a basal/external
lamina
Skeletal myofibers are organized into motor units
A motor unit is defined as one motor neuron and all of the myofibers it innervates
All myofibers in a motor unit are composed of identical fiber types in terms of the type of
myosin (fast or slow) that they synthesize and the profile of their metabolic enzymes.
the myofibers in motor units are usually scattered in different fascicles within the body of the
muscle
They type and number of motor units recruited for a particular task depend upon the amount of
force and or finesse that is required
When a skeletal myofiber is denervated due to disease, age, or injury, it goes through a series of
degenerative changes that decrease its diameter
o this process is called atrophy
If denervated long enough, the fiber disappears entirely
The myofibers are categorized as fast, intermediate, or slow fibers based on the type of myosin
and the metabolic enzymes they contain
Fiber type is dictated by the motor neuron that innervates the fiber
Different muscles have distinctive profiles of fiber types that reflect their function
In most human muscles, the fiber types ( and therefore motor units) are intermixed
The precise percentage of each fiber type within a given muscle varies among individuals, and is
determined mainly by genetics
Individuals with a high percentage of red muscle in their lower extremities might excel at long
distance running events
People with a high percentage of white fibers might do better at high jump
An I band contains thin filaments
An A band contains thick filaments
The thick filaments are cross-linked at the M line
The Thin filaments are cross-linked at the Z line
The A band contains the thick filament myosin
o in striated muscle myosin is found exclusively in the thick filaments
o striated muscle myosin is a long, slender molecule composed of 6 subunits, four light
chains and two heavy chains
o the paddle-shaped heads have actin binding sites and an ATPase
o there are two flexible hinge regions where the heads bend during the contraction cycle
o Many myosin hexamers self-assemble into a bipolar, thick filament by interdigitating
their tails so that half of them are aligned with their head pieces to the right, and the
other half with their head pieces to the left
o
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The middle third of the thick filament, made up entirely of the interdigitating tails, is
bare, with no head pieces on its surface
o The two ends, appear rough due to the headpieces sticking out from the surface
M line/band
o The thick filaments are held in their arrangement by M-line proteins, which bind to a
number of thick filaments at the middle of their bare regions
o The M line lies in the middle of the A band
The I band
o Contains thin filaments that is composed of actin, tropomyosin and troponin
o Thin filaments extend perpendicularly from both surfaces of the Z band.
o The portion of two adjoining sarcomeres where there is a common Z band, and thin
filament, but no thick filament is called the I band.
o A sarcomeres is one half I band at either end
Tropomyosin is a slender, rod-like protein that fits into the two grooves of the actin filament.
o Prevents myosin from binding to actin
Troponin is a calcium-sensitive regulatory protein that binds at regular intervals to the thin
filament
o When it binds calcium, troponin changes it shape and moves tropomyosin out from the
groove of the actin filament
o This exposes a myosin binding site on Actin
o Without calcium, troponin relaxes and allows tropomyosin to shield the myosin binding
site
Even in the relaxed state, thin filaments and thick filaments interdigitate to some extend
The portion of the A band that is free of thin filaments in relaxed sarcomeres is called the H
band
Transverse tubules and the sarcoplasmic reticulum (SER)
o All over the surface of the myofiber there are narrow tubular invaginations of the
sarcolemma at the junctions of the A bands and the I bands ( the AI junctions)
o These transverse tubules ( T-tubules) penetrate into the sarcoplasm perpendicular to
the longitudinal axis of the myofiber and continue to travel to the interior of the
myofiber
o T-tubules form a series of “bracelets” that wrap each myofibril at every AI junction along
its length
o Contraction of the myofiber is initiated when the motor neuron stimulates an action
potential, a wave of depolarization that travels along the sarcolemma
o The T-tubules carry the action potential that begins at the neuromuscular unction to the
deepest sarcomeres of the myofiber
o Contraction of successive sarcomeres occurs as a single synchronous wave traveling
down the myofiber
o As the T-tubules travel through the sarcoplasm, they are always in contact with the
sarcoplasmic reticulum (SR)
o
o
o
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The SR regulates the concentration of calcium in the sarcoplasm
In the relaxed state, the SR contains a high concentration of calcium, while the calcium
concentration in the sarcoplasm is very low
Upon stimulation by the action potential, the SR releases calcium into the sarcoplasm
initiating the contraction cycle
At every AI junction there is a T-tubule squeezed in between a pair of dilated SR cisterns
called lateral expansions.
 This configuration is called the triad
4. Define myofibril and myofibers.
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Myofibers refers to a cell
Myofibril refers to an intracellular set of proteins
5. Describe the role of muscle spindles in skeletal muscle.
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Skeletal muscle contraction is monitored by sensory receptors ( proprioceptors) called muscle
spindles
Spindles monitor the length of the muscle ( the state of contraction) and the rate of contraction
Each spindle is surrounded vy a cellular layer called perineurium
Inside the sheath there are very small specialized myofibers called intrafusal fibers ( fibers inside
the spindle)
Typical contractile myofibers are called extrafusal fibers ( myofibers outside the spindle)
There are two types of intrafusal fibers
o Nuclear bag fibers have all their nuclei located in one, mid-fiber enlargement
o Nuclear chain fibers have their nuclei lined up single file down the center of the fiber
6. List the locations of smooth muscle.
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Smooth ( non-striated muscle) is named based off of its appearance
The cytoplasm is featureless and glassy
The boundaries between individual myocytes are difficult to distinguish
Found predominantly in the walls of the vascular system, and the digestive, reproductive,
respiratory and urinary systems
Cell shape
o Relaxed, smooth muscle myocytes have the form of long slender spindles
o The only organelle that is ordinarily visible in the light microscope is the nucleus
o At rest, in longitudinal view, the nucleus is cigar-shaped with smooth border
o The nucleus is located in the middle of the cell, halfway between the ends
o When myocytes are grouped together, the slender end of one cell overlaps the thick
middle portions of the adjacent myocytes, so there is very little extracellular connective
tissue space
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The resting length of the myocytes is dependent on its location and it can range from a
few microns to several millimeters
o In the contracted cell the sarcolemma and the nuclear membrane are corrugated like an
accordion or a ruffled potato chip
Distribution
o Smooth muscle myocytes can occur as isolated cells and slender groups of a few cells
 Their configuration is usually linear, with an origin and insertion
o Most smooth muscle in humans is found in the walls of tubes such as arteries and
intestines
 The myocytes are grouped together in long, overlapping, helical bands that wind
around the tubes.
7. Explain the relationship of smooth muscle cells to their connective tissues and vasculature.
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Smooth muscle myocytes depend on connective tissues for their nutrition and in some
situations, for transmission of the force they generate
Individual myocytes and linear groups are attached by fibronectin and collagen fibers to the
structures they move
Helical bands and layers attach to each other, exerting their force on the lumen they surround
There are three major divisions of CT associated with smooth muscle
o Endomysium
 Consists of type III collagen fibrils that are secreted by the smooth muscle cells
o Perimysium
 When myocytes are organized into helical bands, or fascicles, as in the
respiratory or digestive organs, adjacent bands are separated from each other
by layers of Perimysium that contain vessels and nerves
o Epimysium
 There are some instances where the entire smooth muscle is defined and
enclosed by a denser CT that provides slippage planes between adjacent muscle
bundles
 One example is the wall (myometrium) of the uterus
8. Compare and contrasts unitary vs. multiunit smooth muscle, including their locations and
innervations requirements.
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Unitary ( visceral) smooth muscle
o Found in the walls of many of the viscera including: urinary tract, reproductive tract,
digestive tract, respiratory system
o Share several properties with cardiac muscle:
 Innervations- one nerve ending innervates many myocytes
 Unitary muscles are only partially dependent on their innervations.
 They can contract without innervation, but innervations can modify the
contraction frequency
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Sensory neurons are required
There are groups of myocytes that respond to stimuli such as stretch and
generate action potentials spontaneously.
In the unitary muscle of the digestive tract, these pacemaker regions, not the
innervation, initiate peristalsis
Multiunit Smooth Muscle
o Examples are the ciliary muscle, the dilator and sphincter of the pupil, and the smooth
muscle in the eyelid
o In the walls of blood vessels
( all arteries and large veins)
o Because most multiunit muscle is found in the vascular system, it is also called vascular
smooth muscle.
o Multiunit smooth muscle has several properties similar to those of skeletal muscle:
 One neuron innervates a few myocytes
 The neuromuscular junctions in smooth muscle are less complex than those in
skeletal muscle
 The myocytes cannot function after denervation because they require motor
innervation to initiate contraction
 The myocytes are organized into motor units
 Unlike visceral muscle, multiunit myocytes have no pacemaker region and
depend instead on their motor neurons
 There are few to no gap junctions between myocytes in multiunit muscle
9. Describe the function of the gap junction of the smooth muscle myocyte.
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adjacent myocytes are connected to each other by gap junctions
myocytes are organized into fascicles that are arranged in helices around a lumen
all the myocytes within a fascicle are in electrical continuity with each other
each fascicle has a pacemaker at the cranial end, so that action potentials spread via the gap
junctions from cranial to caudal in a peristaltic wave along the fascicle
in the intestine smooth muscle contraction can be controlled locally by innervation from a
myenteric plexus
10. Discuss the structure of smooth muscle contractile proteins and how they interact.
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Each myocyte has a complete external lamina over its plasmalemma except where there are gap
junctions
Within a fascicle there is very little endomysial connective tissue separating adjacent myocytes
Unitary myocytes send out a number of slender processes that meet those from adjacent cells
and form gap junctions
The sarcoplasm is dominated by filaments, mitochondria scattered among the filaments, and
some smooth vesicles, especially next to the plasmalemma
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These are pinocytotic vesicles and rudimentary sarcoplasmic reticulum
Other organelles such as RER, Golgi apparatus, a centriolar pair, etc, are located at either pole of
the nucleus in the two conical regions where there are no filaments
Thin Filament
o Thin filaments dominate the sarcoplasm
o They are composed of actin and tropomyosin, but lack troponin
o Anchored at one end to a very compact clump of filaments called a dense body
Thick Filament
o Myosin is present in the sarcoplasm of smooth muscle myocytes
o Controversy over what it looks like
o In most electron micrographs myosin structures are not identifiable, even though they
are known to be present
o Sometimes they look like ribbons, while other times they look like rods are very thick
filaments
Intermediate filament
o Desmin is the intermediate filament
o Less numerous than the thin filaments
o Desmin bundles run parallel to the thin filaments
o Anchored to dense bodies at both of their ends
o Provide structural support for the myocyte
Dense Bodies
o Composed of the filamentous protein alpha-actinin
o Found throughout the sarcoplasm and can also be membrane-associated, attached to
the inner surface of the sarcolemma
o Cytoplasmic dense bodies are equivalent of the Z bands in striated muscle
o Membrane-associated dense bodies are comparable to the insertion sites of the
sarcomeres into the sarcolemma at the end of skeletal myofibers and at the intercalated
disks of cardiac myocytes
Function
o Contract slow compared to striated muscle
o Unitary smooth muscle contracts particularly slow, but with a much greater
force/weight ratio
o Unitary smooth muscle can maintain contraction for long periods ( days) with little or no
expenditure of energy because of the mechanism of smooth muscle contraction
11. List the secretory products of smooth muscle.
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Smooth muscle cells secrete elements of the extracellular matrix
Most prominent example of secretory activity of these cells is in the wall of large, elastic
arteries, such as the aorta
These myocytes have a well-developed RER and Golgi apparatus, and synthesize elastin in the
form of membranes
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Specialized smooth muscles cells in the kidney secrete rennin, which plays a role in the
regulation of blood pressure
12. Describe smooth muscle regeneration.
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Smooth muscle cells in the adult are often quiescent, but are capable of reentering the mitotic
cycle following injury or as part of a disease state
Some smooth muscle cells, such as those in the uterus, the gut or in blood vessels, undergo
regular cycles of mitosis
13. Explain how smooth muscle is affected in hypertension and Hirschsprung’s disease.
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Hypertension
o High blood pressure can arise from prolonged contraction of vascular smooth muscle
o Hypertension can lead to increased risk of heart attack and stroke
o Commonly treated with diuretic drugs, angiotensin converting enzyme inhibitors, and
lifestyle modifications
Hirschsprung’s disease
o The terminal portion of the intestine is not innervated due to congenital defections
o Surgical intervention is usually required